Biomedical subjects
J Weiner
Publications and source records attributed to J Weiner.
Clinical staffing in staff- and group-model HMOs.
Analysts frequently have used health maintenance organization (HMO) staffing patterns as a yardstick for estimating national clinical workforce requirements. Based on a nationwide survey of fifty-four staff- and group-model HMOs, the largest sample yet used in an analysis of this type, this DataWatch examines physician-to-member ratios, the use of nonphysician providers, and HMOs' methods of estimating clinical staffing needs. Overall physician staffing ratios and primary care physician staffing ratios closely resemble those reported in previous studies, but they exhibit wide variability and are strongly correlated with HMO size. Although caution should be exercised when using HMO staffing ratios in projections of physician workforce requirements, the ratios described here support projections of a specialty physician surplus.
Financing long-term care. A proposal by the American College of Physicians and the American Geriatrics Society.
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Cloning and functional expression of a cyclic-nucleotide-gated channel from mammalian sperm.
Cyclic nucleotide-gated (CNG) channels serve as downstream targets of signalling pathways in vertebrate photoreceptor cells and olfactory sensory neurons (see ref. 1 for review). Ca2+ ions that enter through CNG channels intimately control these signalling pathways by regulating synthesis or hydrolysis of cyclic nucleotides, and by decreasing ligand sensitivity of CNG channels. Several lines of evidence suggest that cyclic nucleotides and Ca2+ play important roles in chemotaxis of invertebrate sperm and fertilization (see ref. 9 for review), whereas their mechanisms of action in vertebrate sperm are largely unknown. Here we report the cloning and functional expression of a novel CNG channel from bovine testis. The channel polypeptide was functionally localized in sperm, but is also specifically expressed in cone photoreceptor cells. These channels might be involved in chemotaxis of sperm by controlling Ca2+ entry through a cyclic-nucleotide signalling pathway.
C1-esterase inhibitor concentrate prevents upper airway obstruction in hereditary angio-oedema.
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Development of the Leeds Dependence Questionnaire (LDQ): a questionnaire to measure alcohol and opiate dependence in the context of a treatment evaluation package.
The Leeds Dependence Questionnaire (LDQ) has been developed as part of a treatment evaluation package. The LDQ is a 10-item, self completion questionnaire designed to measure dependence upon a variety of substances; it has been shown to be understood by users of alcohol and opiates. The questionnaire was designed to be sensitive to change over time and to be sensitive through the range from mild to severe dependence; the follow-up data are insufficient to demonstrate change over time, but are encouraging. It is expected that both clinicians and researchers will find it useful to have a single measure relating to substance use, but not limited by specific substances. All items are scored 0-1-2-3; there are no normative data. The procedure for establishing content validity is described and estimates of concurrent, discriminant and convergent validities are reported; these validities are thought to be satisfactory. A principal components analysis produced a single factor accounting for 64% of the variance. Cronbach's alpha was 0.94. Test-retest reliability was found to be 0.95.
Expanding the ANNA scope of practice.
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Differential inhibition by NMDA antagonists of rapid tolerance to, and cross-tolerance between, ethanol and chlordiazepoxide.
We have recently found that the non-competitive N-methyl-D-aspartate (NMDA) antagonists, (+)MK-801 and ketamine, block the development of rapid tolerance to ethanol. In the present report we show that they also block rapid cross-tolerance from chlordiazepoxide to ethanol as well as ethanol to chlordiazepoxide. However, NMDA antagonists fail to block the development of rapid tolerance to chlordiazepoxide. Our results suggest that NMDA antagonists may affect not only the acquisition of rapid tolerance or cross-tolerance to sedatives but also the ability to express that tolerance or cross-tolerance, depending on the drugs used. It is also possible that the phenomena of rapid tolerance and rapid cross-tolerance have basic differences not previously reported in the literature.
Malignant lymphoproliferative diseases in occupations with potential exposure to phenoxyacetic acids or dioxins: a register-based study.
The Swedish Cancer Environment Register (CER) is a linkage of census data (e.g., on occupations) with the Swedish Cancer Register. It has been used in different studies to generate hypotheses on occupational risk factors for malignant tumors. In this study the risk for malignant lymphoma and multiple myeloma in occupations with potential exposure to phenoxyacetic acids or other related substances were investigated. An increased standardized incidence ratio (SIR) of 1.3 for multiple myeloma was verified in farmers (no. of cases = 335). This finding applied to both sexes, and the SIR increased over successive time periods. Regarding malignant lymphoma an increased SIR of 1.2 was found in farmers (no. = 227) for the latest time period studied (i.e. 1979-1984). When non-Hodgkin's lymphoma was studied separately, an increased risk (SIR = 1.2) was found only in carpenters (no. = 149), whereas for Hodgkin's disease, sawmill workers (no. = 10) had an increased SIR of 2.1. Physicians also had an elevated risk for malignant lymphoma. A major shortcoming in register studies such as CER is that no individual exposure data on different agents are available. Lack of an association between an occupation and a specific malignant disease, therefore, may not be taken as evidence that persons within that occupation are not at increased risk for that disease.
Rapid tolerance and cross-tolerance as predictors of chronic tolerance and cross-tolerance.
Hypothermia and motor impairment (tilt-plane) tests were used to assess the phenomenon of rapid tolerance to ethanol and cross-tolerance to various alcohols, benzodiazepines, and barbiturates that differ in lipid:water partition coefficients. The hypothermic and motor impairment responses to ethanol were significantly reduced on day 2 in rats receiving ethanol (2 doses of 2 g/kg each for the hypothermia test and 2.3 and 1.7 g/kg for the tilt-plane test) 24 and 22 h earlier compared to the control group pretreated with saline. Ethanol pretreatment resulted in rapid cross-tolerance, on both tests, to the various alcohols (n-propanol, n-butanol, and t-butanol) and the benzodiazepines (chlordiazepoxide, diazepam, oxazepam, and flurazepam) tested. Ethanol pretreatment also conferred clear rapid cross-tolerance to barbital and phenobarbital, but did not result in rapid cross-tolerance to pentobarbital, secobarbital, amobarbital, or thiopental. The results on rapid cross-tolerance on both tests seen in these studies parallel the results obtained in chronic tolerance and cross-tolerance studies reported recently. These results suggest that rapid tolerance and cross-tolerance can be used as predictors of chronic tolerance and cross-tolerance.
Ketamine retards chronic but not acute tolerance to ethanol.
Motor impairment (tilt-plane test) was used to investigate whether the noncompetitive N-methyl-D-aspartate (NMDA) antagonist ketamine prevents the development of chronic and acute tolerance to ethanol. Rats were treated with ethanol or saline in the presence and absence of ketamine (separate groups) for 10 days and tested for ethanol tolerance in the absence of ketamine on the fifth and tenth days. In other studies, the effect of ketamine on acute tolerance to ethanol was examined. Rats that received ethanol daily without ketamine showed significant tolerance to ethanol on days 5 and 10, but those receiving ethanol plus ketamine daily showed significantly less tolerance to ethanol. Thus, ketamine interfered with the development of chronic tolerance just as it had been found previously to prevent rapid tolerance. In contrast, ketamine failed to block acute tolerance to ethanol. These results would suggest that the phenomena of acute tolerance and chronic tolerance have differences not previously reported.
Infection risk in patients with small cell lung cancer receiving intensive chemotherapy and recombinant human granulocyte-macrophage colony-stimulating factor.
The effect of recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) was assessed in 17 patients with small cell lung cancer. GM-CSF was initially given alone by subcutaneous injection for 10 days at 50-500 micrograms/m2 per day. There was a significant rise in neutrophils and eosinophils and to a lesser extent in monocytes at all dose levels. During the next phase, patients received chemotherapy (etoposide, ifosfamide and doxorubicin), and GM-CSF was given on alternate cycles, the patients acting as their own controls, so that the amelioration of chemotherapy could be assessed. Despite partial abrogation of the neutropenia associated with chemotherapy (P = 0.04), GM-CSF failed to reduce the frequency of febrile episodes in association with neutropenia, with six episodes occurring on GM-CSF and seven while patients were not receiving GM-CSF after a total of 66 cycles of chemotherapy. After GM-CSF, there was a reduction in polymorph phagocytic ability and chemotaxis in 6/12 and 9/11 patients, respectively. Timed blood counts after GM-CSF administration showed that peak leucocytosis occurred at 8-12 h and fell to two-thirds of this level at 24 h. Toxicity consisting of lethargy, myalgia and bone pain occurred at all dose levels but was manageable. 2 patients had thromboembolism. This study failed to demonstrate a reduction in the infection risk associated with moderately intensive chemotherapy for small cell lung cancer despite the partial abrogation of neutropenia.
Students' attitudes toward informed consent and the physician-patient relationship in regard to human tissue research.
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Combination of GM-CSF and cytosine in myelodysplasia results in improved neutrophil function.
Granulocyte-macrophage colony-stimulating factor (GM-CSF) was given concurrently with low-dose cytosine arabinoside for 3 weeks to patients with myelodysplasia. Neutrophil activation as evidenced by increased chemiluminescence and reduced surface expression of CD16 was consistently seen during therapy. An attendant fall in chemotaxis was also observed. These effects occurred even when neutrophil counts did not rise significantly at lower doses of GM-CSF. Although no improvement in anaemia or thrombocytopenia was observed, the neutrophil counts became normal during therapy without significant expansion of marrow cellularity or colony-forming ability. No major toxicities were observed, even at higher dosages of GM-CSF.
Effects of competitive asymmetry on a local density model of plant interference.
Although competition between plants is usually asymmetric (i.e. larger plants have a disproportionate effect on smaller plants) almost all models of plant competition at the local level have assumed symmetric competition. We add a simple version of competitive asymmetry to the local density neighborhood models of plant interference and population dynamics developed by Pacala & Silander (1985, Am. Nat. 125, 385-411; 1987, Oikos 48, 217-224) by assuming that plants within a neighborhood can be put in a linear dominance hierarchy based upon their initial size. The size of a focal plant is a function of the number of dominant and the number of subordinate neighbors within its neighborhood, with subordinate neighbors having less of an effect than dominant ones. Asymmetry prevents precipitous changes in focal plant size with changes in local density, making the relationship between focal plant size and local density hyperbolic, even if the symmetric model is not hyperbolic. Thus, asymmetry makes the model conform to the law of constant final yield, irrespective of the form of the relationship between plant size and local crowding. Asymmetry also prevents population dynamic oscillations in the model in cases in which it would occur in the absence of asymmetry. The results show that asymmetry has major effects on a model of local interference in plants, and point to the importance of including it in such models.
Recombinant human GM-CSF in small cell lung cancer: a phase I/II study.
Seventeen patients with small cell lung cancer were entered into a dose ranging phase I-II study using rhGM-CSF (Glaxo). In the phase I study patients received 50, 150, 300 or 500 micrograms/m2 GM-CSF for 10 days by daily subcutaneous injection. Full blood counts were performed thrice weekly. After 4 days off all therapy patients then received chemotherapy with doxorubicin 50 mg/m2 i.v. bolus, day 1, ifosfamide 5 g/m2 with mesna 5 g/m2 over 24 h by continuous infusion followed by mesna 3 g/m2, and etoposide 120 mg/m2 i.v. on days 1-3. A total of six courses of chemotherapy were given. In the phase II study patients received the same dose of GM-CSF as in the phase I. GM-CSF was given 24 h after the last dose of chemotherapy for 14 days. Full blood counts were checked thrice weekly and the incidence of infections noted. Patients were randomised to receive GM-CSF with either odd or even courses of chemotherapy. The leucocyte count rose from a mean of 8.7 to 21.6 x 10(9)/l at the 50 micrograms/m2 GM-CSF dosage and from 11.4 to 39.4 x 10(9)/l at the 500 micrograms/m2 dosage during the phase I study. Phase I toxicity was: bone pain in 65% of patients, rash in 47%, fever in 24%, lethargy in 12% and diarrhoea in 12%. In the phase II study the duration of neutropenia was less during the chemotherapy courses with GM-CSF (p = 0.04) but the number of infections was similar.(ABSTRACT TRUNCATED AT 250 WORDS)
Rapid tolerance as an index of chronic tolerance.
Hypothermia and motor impairment (tilt-plane test) were used to assess the phenomenon of rapid cross-tolerance between ethanol and pentobarbital in rats. The hypothermic and motor-impairment responses were significantly reduced on day 2 in animals receiving ethanol on day 1, compared to the control group pretreated with saline. Ethanol pretreatment, however, did not result in rapid cross-tolerance to pentobarbital on either test. Pentobarbital pretreatment on day 1 resulted in rapid tolerance to pentobarbital on day 2. However, in contrast to the lack of rapid cross-tolerance to pentobarbital after pretreatment with ethanol, pentobarbital pretreatment clearly conferred rapid cross-tolerance to ethanol. Determination of ethanol and pentobarbital blood levels suggested that pharmacokinetic alterations did not contribute significantly to the observed rapid tolerance and cross-tolerance. The asymmetry of rapid cross-tolerance seen in these studies mimics the results obtained by us in chronic tolerance and cross-tolerance studies reported recently. These results suggest that rapid tolerance and cross-tolerance can be used as predictors of chronic tolerance and cross-tolerance.