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Biomedical subjects

M Singer

Publications and source records attributed to M Singer.

At least 91 records · Page 5Linked to original sources
PubMed1997

Needle exchange and AIDS prevention: controversies, policies and research.

This paper reviews the key public health issues, social science research, and policy debates that surround the issue of needle exchange as an AIDS prevention strategy among injection drug users. As worldwide rates of drug use-related HIV infection and injection drug use have continued to rise, there is growing public health pressure to identify effective prevention strategies. Needle exchange, while consistently found to be effective in lowering AIDS risk and in preventing new HIV infection, remains a controversial issue in the U.S. because this "harm reduction" approach fails to condemn drug use, suggesting the underlying moral issues in an increasingly intense public policy conflict.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Changing the environment of AIDS risk: findings on syringe exchange and pharmacy sales of syringes in Hartford, CT.

This paper reports findings from a National Institute on Drug Abuse-funded study designed to test the hypothesis that environmental changes, such as the enactment of laws to increase the accessibility of sterile syringes, including syringe exchange and pharmacy sale of syringes without a prescription, will lower the frequency of HIV risk and the prevalence of HIV among street drug users. Project COPE, a study of AIDS risk and risk prevention, collected longitudinal data on drug use, HIV risk, serostatus, and source of syringes in a sample of 710 out-of-treatment injection drug users in Hartford, CT. Findings support the hypothesis and the growing research-based conclusion that syringe exchange is an effective AIDS risk reduction modality.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Evaluation of the antiinflammatory activity of a dual cyclooxygenase-2 selective/5-lipoxygenase inhibitor, RWJ 63556, in a canine model of inflammation.

Sterile perforated polyethylene spheres (wiffle golf balls) were implanted s.c. in beagle dogs. A local inflammatory reaction was elicited within the spheres by injecting carrageenan. Changes in leukocyte count, prostaglandin E2, thromboxane B2 and leukotriene B4 levels were monitored in fluid samples collected over a 24-hr period. Blood samples were also collected at various time points and analyzed for prostaglandin E2 and leukotriene B4 production after ex vivo calcium ionophore treatment. Effects of standard antiinflammatory agents (aspirin, indomethacin, dexamethasone, tenidap and zileuton) and newer cyclooxygenase-2 (COX-2) selective agents (nimesulide, nabumetone and SC-58125) were determined after oral administration. Ex vivo inhibition of cyclooxygenase product synthesis (prostaglandin E2, thromboxane B2) in whole blood was used as an indicator of activity for the constitutive COX-1 isoform, although inhibition of the synthesis of these mediators in the chamber exudate during an inflammatory process is believed to represent COX-2 inhibition. Treatment effects on leukotriene B4 production were also determined both ex vivo in whole blood and in the fluid. All of the compounds tested, except aspirin, inhibited leukocyte infiltration into the fluid exudate. Inhibitors that exert their effects on both isozymes of cyclooxygenase attenuate production of cyclooxygenase metabolites in both the inflammatory exudate and in peripheral blood ex vivo, although COX-2 selective inhibitors only demonstrated activity in the exudate. A 5-lipoxygenase inhibitor (zileuton), a corticosteroid (dexamethasone) and a dual COX-2 selective/5-lipoxygenase inhibitor (RWJ 63556) had similar profiles in that they all inhibited cell infiltration and eicosanoid production in the fluid and also attenuated leukotriene B4 production in both the fluid and blood.

Animals↗
PubMed1996

Randomised trial of safety and efficacy of immediate postoperative enteral feeding in patients undergoing gastrointestinal resection.

OBJECTIVES: To assess whether immediate post-operative enteral feeding in patients who have undergone gastrointestinal resection is safe and effective. DESIGN: Randomised trial of immediate post-operative enteral feeding through a nasojejunal tube v conventional postoperative intravenous fluids until the reintroduction of normal diet. SETTING: Teaching hospitals in London. SUBJECTS: 30 patients under the care of the participating consultant surgeon who were undergoing elective laparotomies with a view to gastrointestinal resection for quiescent, chronic gastrointestinal disease. Two patients did not proceed to resection. MAIN OUTCOME MEASURES: Nutritional state, nutritional intake and nitrogen balance, gut mucosal permeability measured by lactulose-mannitol differential sugar absorption test, complications, and outcome. RESULTS: Successful immediate enteral feeding was established in all 14 patients with a mean (SD) daily intake of 6.78 (1.57)MJ (1622 (375) kcal before reintroduction of oral diet compared with 1.58 (0.14) MJ (377 (34) kcal) for those on intravenous fluids (P < 0.0001). Urinary nitrogen balance on the first postoperative day was negative in those on intravenous fluids but positive in all 14 enterally fed patients (mean (SD) - 13.2 (11.6) g v 5.3 (2.7) g; P < 0.005). There was no difference by day 5. There was no change in gut mucosal permeability in the enterally fed group but a significant increase from the test ratios seen before the operation in those on intravenous fluids (0.11(0.06) v 0.15 (0.12); P < 0.005). There were also fewer postoperative complications in the enterally fed group (P < 0.005). CONCLUSIONS: Immediate postoperative enteral feeding in patients undergoing intestinal resection seems to be safe, prevents an increase in gut mucosal permeability, and produces a positive nitrogen balance.

Enteral Nutrition↗
PubMed1996

Fine-needle aspiration as the initial diagnostic modality in malignant lung disease.

Cytologic detection of lung cancer is accepted, accurate, and time-honored. Typically, cytologic workup of a radiologic abnormality proceeds sequentially from sputum to bronchoalveolar cytology, and, if necessary, to fine-needle aspiration biopsy (FNA). Initial use of FNA in lung cancer diagnosis is controversial, but increasingly popular. We therefore decided to objectively assess current practice in cytologic lung cancer diagnosis at our institution. All pulmonary cytologic diagnoses for 1993 and the first half of 1994 were retrieved. Positive diagnoses were then used to access all patient data. Patients were stratified according to the specimen from which the first positive diagnosis was obtained. Of 542 pulmonary cytology specimens, 15% were sputa, 65% were bronchoalveolar, and 20% were FNAs. One hundred sixty-one of 172 malignant diagnoses were first diagnoses. Three percent of first malignant diagnoses were made from sputa, 47% were from lavages, and 50% were from FNAs. Although FNAs comprised just 20% of all pulmonary cytologies, 50% of all new malignant cytologic diagnoses were made by FNA. Initial use of FNA is successful, has a high diagnostic yield and low complication rate, and offers the most direct approach to diagnosis.

Biopsy, Needle↗
PubMed1996

Interleukin-10 inhibits cytokine generation from mast cells.

This report examines the effects of recombinant murine interleukin-10 (rmIL-10) on antigen-induced beta-hexosaminidase, leukotriene (LT)C4 and cytokine release from mouse bone marrow-derived mast cells (BMMC). BMMC sensitized to hapten-monoclonal IgE directed against dinitrophenol-bovine serum albumin (DNP-BSA) and challenged with 10 ng/ml DNP-BSA generated beta-hexosaminidase and LTC4-like material which was followed by tumor necrosis factor-alpha (TNF-alpha) and granulocyte-macrophage colony-stimulating factor (GM-CSF) mRNA expression and protein release. Incubation of BMMC with 1-100 ng/ml rmIL-10 inhibited cytokine generation, without affecting beta-hexosaminidase and LTC4-like material release. TNF-alpha, but not GM-CSF mRNA expression, was also diminished in rmIL-10-treated BMMC, suggesting that down-regulation of cytokine production by rmIL-10 involves different mechanisms. These results identify a novel biological action of IL-10 as an inhibitor of cytokine production by stimulated mast cells.

Animals↗
PubMed1996

Constructing and Validating Motive Bridging Inferences

Understanding Jane left early for the birthday party, She spent an hour shopping at the mall requires detecting that the first statement motivates the second. The validation model states that before accepting this bridging inference, the reader validates it with reference to relevant knowledge. In particular, a mediating idea is first derived from the text outcome and its candidate motive. If the mediating idea is supported by general knowledge, then the inference has been validated. In tests of this anaylsis, experimental subjects read motive or control sequences and then answered questions probing the knowledge hypothesized to validate the motive inferences, such as Do birthday parties involve presents? Five experiments confirmed that understanding motive sequences facilitates validating knowledge. A control procedure also refuted a priming counterexplanation of these effects (Experiment 1). Validation processing obtained for motive-outcome statements separated by two to four sentences in coherent sequences (Experiments 2 to 4). Inferred and explicit validating knowledge had a similar representational status (Experiment 3). Whereas proofreading abolished the validation effect, a reading strategy promoting causal processing did not enhance it (Experiment 4). A delayed priming procedure indicated that validating knowledge is integrated with the text representation (Experiment 5). The implications of these findings for the constructionist and minimal inference analyses were explored. The validation effects were simulated using construction-integration model.

Journal Article↗
PubMed1996

Bladder epithelial oxygen tension--a new means of monitoring regional perfusion? Preliminary study in a model of exsanguination/fluid repletion.

OBJECTIVE: To assess whether monitoring of bladder epithelial oxygen tension (BEOT) would provide an indication of regional (renal) organ perfusion in an exsanguination/fluid repletion animal model. DESIGN: Prospective non-randomized laboratory study. SETTING: Research laboratory. INTERVENTIONS: Eight anaesthetised, spontaneously breathing Sprague-Dawley male rats weighing approximately 200 g were instrumented. They received 1-ml aliquots of fluid until no further haemodynamic improvement was seen, followed by removal of 1-ml aliquots of blood until renal blood flow fell by 50%. The animal was then resuscitated with repeated 1 to 2-ml aliquots of fluid until no further improvement was achieved and, finally, progressively exsanguinated to cardiovascular collapse. MEASUREMENTS AND RESULTS: A continuous Clark-type oxygen electrode lying in contact with the inside wall of the bladder measured changes in BEOT during these exsanguination and fluid repletion manoeuvres. Changes in BEOT closely mirrored both systemic (blood pressure and aortic blood flow) and regional (renal blood flow) haemodynamic changes. A direct correlation existed between percentage change in BEOT and base deficit, and an indirect correlation was seen with arterial oxygen tension. CONCLUSIONS: Measurement of BEOT may be a useful and relatively non-invasive means of monitoring regional organ perfusion. Further studies are warranted.

Animals↗
PubMed1996

Evaluation of agonist-antagonist properties of nitrogen mustard and cyano derivatives of delta 8-tetrahydrocannabinol.

delta 8-Tetrahydrocannabinol (delta 8-THC) is a naturally occurring cannabinoid with a characteristic pharmacological profile of in vivo effects. Previous studies have shown that modification of the structure of delta 8-THC by inclusion of a nitrogen-containing functional group alters this profile and may alkylate the cannabinoid receptor, similar to the manner in which beta-funaltrexamine (beta-FNA) alkylates the micro-opioid receptor. Two novel analogs of delta 8-THC were synthesized: a nitrogen mustard analog with a dimethylheptyl side chain (NM-delta 8-THC) and a cyano analog with a dimethylpentyl side chain (CY-delta 8-THC). Both analogs showed high affinity for brain cannabinoid receptors and when administered acutely, produced characteristic delta 9-THC-like effects in mice, including locomotor suppression, hypothermia, antinociception and catalepsy. CY-delta 8-THC shared discriminative stimulus effects with CP 55,940; for NM-delta 8-THC, these effects also occurred, but were delayed. Although both compounds attenuated the effects of delta 9-THC in the mouse behavioral tests, evaluation of potential antagonist effects of these compounds was complicated by the fact that two injections of delta 9-THC produced similar results, suggesting that acute tolerance or desensitization might account for the observations. NM-delta 8-THC, but not CY-delta 8-THC, attenuated the discriminative stimulus effects of CP 55,940 in rats several days following injection. Hence, addition of a nitrogen-containing functional group to a traditional cannabinoid structure does not eliminate agonist effects and may produce delayed attenuation of cannabinoid-induced pharmacological effects.

Animals↗
PubMed1996

Episodic evolution and rapid divergence of members of the rat multigene family encoding the salivary prohormone-like protein SMR1.

In rodents, the variable coding sequence (VCS) multigene family displays extensive evolutionary divergence in the protein-coding region. While certain VCS genes coding for proline-rich proteins (hPR-PB, mMSG1, rPR-VB1) are conserved in primates and rodents, others seem to be specific to certain genera. This appears to be the case for the Rattus genes forming the A-subclass. This subclass is composed of three genes in R. norvegicus and probably five genes in R. rattus. The first described VCSA gene (Rn. VCSA1) was found to encode a prohormone-like protein named SMR1 (-VA1), expressed mainly in the submandibular glands (SMG) of male rats. To further understand the evolution of this variable multigene family, we have cloned the two additional genes (Rn. VCSA2 and Rn. VCSA3) forming the R. norvegicus A-subclass and three VCSA genes (Rr. VCSA1a, b and Rr. VCSA2) of R. rattus. The putative SMR1 proteins encoded by all these genes display the same prohormone-like structure as Rn. SMR1-VA1. However, we observe a polymorphism in some internal cleavage sites which suggests that multiple processing of the SMR1 proteins could result in the liberation of peptides differing in structure and length. The phylogenetic analysis of the sequences reveals that the duplication events giving rise to the VCSA1, -A2, and -A3 progenitors were anterior to the R. norvegicus and R. rattus split, and that a VCSA1 duplication event likely occurred specifically in R. rattus. A striking observation is that the coding sequences of the VCSA genes have rapidly diverged from their ancestors. Along all branches of the phylogeny, the nonsynonymous divergence rate is identical or superior to the synonymous divergence rate. We suggest that frequent changes in functional requirements are mainly responsible for the episodic evolution and the rapid divergence of the VCSA genes.

Amino Acid Sequence↗
PubMed1996

Cardiorespiratory and tissue oxygen dose response to rat endotoxemia.

The dose response to endotoxin (Escherichia coli serotype 127:B8) was assessed in a spontaneously breathing, halothane-anesthetized, Sprague-Dawley rat model monitoring blood pressure, aortic and renal blood flows, blood gases, and bladder epithelial PO2, a marker of organ perfusion. The animals received either saline or endotoxin at doses of 1, 10 and 100 mg/kg body wt. Blood pressure changed significantly in all three endotoxin groups, though only the 100 mg/kg group showed significant changes in arterial PCO2, arterial PO2, and body temperature compared with controls. Whereas aortic and renal blood flow rose significantly in the two lower-dose groups, an approximate one-third fall occurred in the 100 mg/kg group (P < 0.001). Notwithstanding these macrocirculatory hemodynamic changes, both bladder epithelial PO2 and arterial base deficit rose significantly in all groups, though only the base deficit showed a progressive dose response. This model illustrates that responses to endotoxin are dose dependent but with changing patterns for different variables. The consistent finding of an elevated tissue PO2 in endotoxemia, regardless of dose, is suggestive of defective cellular oxygen metabolism.

Animals↗
PubMed1996

Farewell to adaptationism: unnatural selection and the politics of biology.

This article argues that human adaptation has lost its utility as a conceptual tool for either biological or medical anthropology, despite the recent efforts of practitioners in these subdisciplines to rescue it by considering the influences of power, history, and global social processes. It draws on cases from diverse fields, including evolutionary studies, ethology, genetics, and epidemiology, to suggest new ways of conceptualizing the relationship between humans and their physical and biotic environments; environments that they, and to a lesser degree other species, are not so much "adapting to" as transforming, while being transformed themselves in the process. Central to this reconceptualization is an understanding of human behavior and environmental relationships in political-economic context.

Adaptation, Psychological↗
PubMed1996

The role of working memory capacity and knowledge access in text inference processing.

Individual differences in drawing bridging inferences during text comprehension were examined. We measured reader differences in working memory capacity, using the reading span task, and in access to relevant knowledge, using Potts and Peterson's (1985) integration task. The dependent measure of greatest concern was answer time about facts posited to validate the bridging inference. Reading span and access were negligibly correlated, an outcome that supports their independence. Answer times were lower both for high reading span and high-access readers. In addition, readers who were either high on both reader traits or low on both traits exhibited qualitatively different inference effects from the typical pattern. It is proposed that knowledge access during comprehension is facilitated by the extraction of integrated situation models from text and that it is individuals with efficient reading processes who can construct these models.

Analysis of Variance↗