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Biomedical subjects

J Weiner

Publications and source records attributed to J Weiner.

At least 73 records · Page 4Linked to original sources
PubMed1992

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.

Animals↗
PubMed1992

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.

Agricultural Workers' Diseases↗
PubMed1992

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.

Alcohols↗
PubMed1992

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.

Animals↗
PubMed1992

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.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

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.

Antigens, CD↗
PubMed1991

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.

Ecology↗
PubMed1991

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)

Adult↗
PubMed1991

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.

Animals↗
PubMed1991

NMDA antagonist inhibits rapid tolerance to ethanol.

To test whether N-methyl-D-aspartate (NMDA) receptors have a role in the development of ethanol tolerance, (+)MK-801, an NMDA antagonist, and (-)MK-801, an inactive isomer, were tested in a rapid tolerance paradigm. Results showed that (+)MK-801 blocked the development of rapid tolerance to ethanol in the tilt-plane and hypothermia tests, while (-)MK-801 was ineffective. Neither drug changed the blood ethanol levels in the treated and untreated animals. These data suggest that the known role of NMDA receptors in long-term synaptic facilitation may underlie the effect of learning in the development of tolerance to the motor-impairing and hypothermic effects of ethanol.

Animals↗
PubMed1991

Identification of jack-jumper ant (Myrmecia pilosula) venom allergens.

Jack-jumper ant venom proteins were electrophoretically separated on SDS-polyacrylamide gels, transferred to nitrocellulose and probed with sera from subjects who had experienced an allergic reaction after being bitten by a jack-jumper ant. Ant venom components that bound IgE antibodies were detected by addition of 125I-anti-human IgE followed by autoradiography. Of the 17 polypeptides resolved by electrophoresis only three, of molecular weights approximately 14 kD, 12 kD and 10 kD, bound IgE antibodies from the panel of 50 sera examined. There was a marked similarity in the binding patterns by individual sera with almost all of the sera recognizing the 14kD and 12 kD components. IgE-binding profiles of separated ant venoms from ants collected in different regions of Australia appeared to be very similar if not identical. Identification of the ant allergens is a necessary prelude to the preparation of standardized venom sac extracts suitable for safe and effective diagnostic and therapeutic use.

Allergens↗
PubMed1991

Mercury and selenium concentrations and their interrelations in organs from dental staff and the general population.

Mercury (Hg) and selenium (Se) concentrations were determined by radiochemical neutron activation analysis in samples from the pituitary glands, occipital cortices, renal cortices, abdominal muscles, and thyroid glands of cadavers. Samples were retrieved from dental staff occupationally exposed to Hg and from the general population. Increased concentrations of both Hg and Se in samples from dental staff showed that Se accumulated together with Hg. Regression analysis of data from the pituitary glands and occipital cortices of dental staff indicated the accumulation of Se at a rough stoichiometric ratio of 1:1 with Hg. The same stoichiometric ratio between the elements was seen in the renal cortices from the general population. The regression analysis showed that a substantial fraction of Se was not associated with Hg; it is assumed that this corresponds to biologically available Se. Concentrations of biologically available Se decreased with advancing age in the pituitary gland, but not in other organs, and varied appreciably between organs.

Abdominal Muscles↗
PubMed1991

Ambulatory care groups: a categorization of diagnoses for research and management.

This article describes a case-mix measure for application in ambulatory populations. The method is based primarily on categorization of diagnoses according to their likelihood of persistence. Fifty-one combinations (the ambulatory care groups or ACGs) result from applying multivariate techniques to maximize variance explained in use of services and ambulatory care charges. The method is tested in four different HMOs and a large Medicaid population. The percentage of the population in each of the 51 categories is similar across the HMOs; the Medicaid population has higher burdens of morbidity as measured by more numerous types of diagnoses. Mean visit rates for individuals within each of the 51 morbidity categories are generally similar across the five facilities, but these visit rates vary markedly from one category to another, even within groupings that are similar in the number of types of diagnoses within them. Visit rates for individuals who stay in the same ACG were similar from one year to the next. The ACG system is found useful in predicting both concurrent and subsequent ambulatory care use and charges as well as subsequent morbidity. It provides a way to specify case mix in enrolled populations for research as well as administration and reimbursement for ambulatory care.

Adolescent↗