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Biomedical subjects

J Cohen

Publications and source records attributed to J Cohen.

At least 577 records · Page 32Linked to original sources
PubMed1996

Characteristics of drug misusers and their perceptions of general practitioner care.

BACKGROUND: Little is known about drug misusers' views of the care they receive from general practitioners. AIM: This study set out to determine drug users' views about primary health care and their relationship with their general practitioners. METHOD: A semi-structured interview was conducted with 180 drug users who were consecutive attenders at five treatment services in north east London--a general practice with a special interest in treating drug users, a private drug clinic, a community drug team, a drug dependence unit and a street agency for drug users. RESULTS: The majority of the 145 London-based drug users attending the four treatment centres other than the general practice with a special interest were registered with a general practitioner (88%). Forty-two per cent of users sought out a general practitioner prepared to treat them, rather than register with a local or the family doctor. Most drug users reported that their general practitioners were aware of their drug problems (88%) but half of the general practitioners were not prescribing replacement drugs with almost 20% of the users not receiving prescriptions claiming that this was due to lack of knowledge or trust on the part of the doctor. Sixty per cent of the drug users attending the four centres perceived that their general practitioners held negative or neutral views about them. However, 34 of the 35 drug users interviewed in the specialist general practice believed their doctors had a positive view of drug users. CONCLUSION: Most drug users were registered with general practitioners but the relationship between doctor and patient was not always easy or productive. There is a need to clarify the role of general practitioners in this field and provide them with better educational opportunities.

Adolescent↗
PubMed1996

The cation distribution set by surface charges explains a paradoxical membrane excitability behavior.

It is widely accepted that divalent cations can affect membrane excitability by interacting with negative charges on the membrane surface. This effect is generally supposed to arise from a modulation of the surface charge electrostatic field within the membrane. As an alternative mechanism, we propose that this effect may also be due to a generalized coupling between ion currents mediated by ionic composition changes at the membrane surface. To test this hypothesis we have computed the transmembrane potential using ionic current relations in which bulk external Ca2+ and K+ activities are substituted with superficial activities deduced from a Grahame-Langmuir isotherm. The model behavior agrees well with published results on Paramecium electrophysiology and furthermore explains 2 paradoxical observations on the cell membrane excitability upon changes of external Ca2+ and K+.

Animals↗
PubMed1996

Erythropoietin stimulates atrial natriuretic peptide secretion from adult rat cardiac atrium.

Hypoxia is a powerful stimulus for erythropoietin (EPO) secretion from the kidney and for atrial natriuretic peptide (ANP) secretion from atrial myocytes. EPO is involved in the long term defense mechanism against hypoxia via stimulation of erythropoiesis. ANP is involved in the short-term defense mechanism against hypoxia via improved pulmonary and heart functions. We investigated a possible interaction between these two hormones. We tested the hypothesis that EPO may stimulate ANP secretion from the cardiac atrium. This hypothesis was tested in two in vitro models; isolated rate atrium and cultured adult atria rat myocytes. Recombinant human EPO (5-10 units/ml) enhanced ANP secretion from the isolated atrium (by approximately 2-fold) within 10 min in a concentration-dependent manner. To define whether the action of EPO on ANP secretion is direct, we examined the effect of EPO on ANP release from adult rat cultured atrial myocytes. EPO failed to stimulate ANP secretion from cultured atrial myocytes, suggesting that EPO-induced ANP secretion is an indirect effect. Cyclooxygenase products (e.g.,prostaglandins) and endothelin 1 were shown to be potent secretagogues of ANP from cardiac atrium. To test whether EPO-induced ANP secretion from isolated perfused atrium is mediated by cyclooxygenase products and/or endothelin, we used inhibitors of the enzyme cyclooxygenase (indomethacin or aspirin) and the endothelin receptor ETA subtype antagonist BQ123. EPO-stimulated ANP secretion was not affected by indomethacin (10(-4) M) or aspirin (10(-4) M), whereas BQ123 (10(-6) M) completely abolished EPO-stimulated ANP secretion from cardiac atrium. Our results expand our knowledge on the interaction between EPO and ANP hormonal systems and the possible role in the acute defense mechanism against hypoxia.

Animals↗
PubMed1996

Sir William Hingston.

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.

Canada↗
PubMed1996

Hypertension and diabetes among Siberian Yupik Eskimos of St. Lawrence Island, Alaska.

CHANGING DIETS AND LIFESTYLES contribute to an increase in the prevalence of cardiovascular disease and diabetes in Alaska Natives. To examine the problem in detail, we have begun a systematic screening of various ethnic groups by carrying out a pilot study of Siberian Yupik Eskimos ages 39 and over. Mean LDL and HDL levels were 157 mg/dl and 63 mg/dl. Mean fasting insulin was 7.0 microunits/ml; and mean BMI, 27.1. Fasting insulin level was significantly related to both diastolic blood pressure and fasting triglyceride levels, but not to systolic blood pressure, total cholesterol, LDL cholesterol, or HDL cholesterol levels. Of the 66 people screened, 27% had evidence of hypertension.

Adult↗
PubMed1995

Do monoclonal antibodies and anticytokines still have a future in infectious diseases?

The continuing high mortality of septic shock has prompted a major effort by the research community to identify novel therapeutic targets. These targets can be conveniently grouped into (1) those derived from microbial components or products; (2) inflammatory mediators; and (3) effector molecules. Many of the experimental, so-called adjunctive agents developed have been monoclonal antibodies or anticytokine molecules of various kinds, and some have progressed into clinical trial. Unfortunately, these trials have failed to show unequivocal survival benefit for patients in shock, prompting a reappraisal of our approach to these agents. In this article, we discuss the possible reasons for these failures: (1) the targets are wrong; (2) the agents are inappropriate; or (3) the trial design is flawed. It would be premature to conclude that adjunctive agents have no future in the therapy of sepsis, but identifying the correct agent, and perhaps more importantly, the correct target population, is going to be more difficult than was at first believed.

Animals↗
PubMed1995

Origins and clinical implications of aneuploidy in early bladder cancer.

Cytogenetic and flow cytometric studies in a variety of human solid tumors have suggested that gross aneuploidy may arise by a process of abrupt chromosome complement doubling followed by gradual chromosome loss. However, this sequence has not been demonstrated directly in serial studies in individual patients in vivo. The purpose of this study was to search for evidence of chromosome complement doubling and subsequent chromosome loss in flow cytometric ploidy patterns in serial bladder washings and/or biopsies from individual patients with early bladder cancer. Fifty-two patients with noninvasive bladder cancer were followed with serial flow cytometric DNA studies for periods ranging from 5.1 to 42.7 months (median 15.1 months). Serial changes in DNA ploidy and S phase fractions were recorded and correlated with histologic and/or cytologic findings, response to treatment and clinical outcome. The data suggest a series of genetic evolutionary changes in early bladder cancer that include the initial development of peridiploid aneuploidy and repeated rounds of DNA content doubling with chromosome loss in patients with progressive disease. It is likely that gross DNA aneuploidy, and more specifically, DNA multiploidy and DNA hypertetraploidy, all arise by this mechanism. The sequence of DNA diploidy, peridiploid aneuploidy, near-tetraploidy, hypotetraploidy and hypertetraploidy is associated with a progressive increase in S phase fraction, and with increasing tumor grade; late steps in this ploidy sequence were often present in tumors that were refractory to local therapeutic measures and tumors that developed deep tumor invasion and/or distant metastases. We conclude that DNA multiploidy and hypertetraploidy are markers of advanced stages of genetic evolution in human bladder cancer.

Adult↗
PubMed1995

The cytokine responsive vascular smooth muscle cell enhancer of inducible nitric oxide synthase. Activation by nuclear factor-kappa B.

The production of inducible nitric oxide synthase (iNOS) within vascular smooth muscle (VSM) cells following exposure to proinflammatory cytokines is a major cause of the vasorelaxation and hypotension of septic shock. We have defined the cytokine-responsive element of the murine iNOS promoter, transfected into a VSM cell line, and the role of the NF-kappa B/Rel family of proteins in iNOS gene activation in these cells. The combination of interleukin-1, interferon-gamma, and tumor necrosis factor-alpha stimulates promoter activity by a factor of 8.1-fold; single cytokines show little activity, while pairs of cytokines produce an intermediate effect. Using a series of promoter deletion mutants, we have defined the cytokine-responsive element from position -890 to -1002; this region contains an NF-kappa B-binding site as well as a number of interferon response elements. Nuclear proteins from cytokine-stimulated VSM cells which bind to an oligonucleotide containing this kappa B site are composed of p65 together with an unidentified protein of 50 kDa, which is not a known Rel family member. A promoter mutant with a 2-base pair change within this kappa B site, which abolishes NF-kappa B binding, has an activity of only approximately 34% (S.E. +/- 1.5) of the wild-type promoter. In addition, protein binding to this site is abolished by a specific inhibitor of NF-kappa B activation, which also abrogates iNOS activity. Residual inducibility in such mutant promoters is attributable to the presence of an independently functioning downstream kappa B site (-85 to -75). The mechanism by which NF-kappa B activates the iNOS promoter in VSM cells in response to cytokines appears to be markedly different to that operative in macrophages in response to lipopolysaccharide.

Animals↗