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Biomedical subjects

M Cohen

Publications and source records attributed to M Cohen.

At least 145 records · Page 8Linked to original sources

The role of low-molecular-weight heparins in arterial diseases: optimizing antithrombotic therapy.

On the basis of current evidence, all patients with acute coronary syndromes should receive optimized medical therapy, whether or not they ultimately undergo an invasive revascularization procedure, to improve both clinical outcomes and cost effectiveness. While standard aspirin and unfractionated heparin (UFH) have improved short-term outcomes, they do not eliminate the risk of recurrent ischemic episodes. The recent introduction of platelet fibrinogen receptor antagonists and low-molecular-weight heparins (LMWHs) has offered an opportunity to develop more aggressive antithrombotic regimens. The LMWHs have been thoroughly evaluated in unstable angina and non-Q wave myocardial infarction (UA/NQMI), and have demonstrated improved efficacy compared to standard UFH, without an increase in major complications caused by bleeding. Experience has also been gathered using LMWHs in other arterial diseases (such as pregnant patients with prosthetic heart valves) and as an adjunctive therapy with thrombolytics for acute myocardial infarction. Lastly, studies are currently underway evaluating LMWHs in patients with atrial fibrillation.

Anticoagulants↗

The relationship between virus load response to highly active antiretroviral therapy and change in CD4 cell counts: A report from the Women's interagency HIV study.

The relationship between the pattern of virus load response to highly active antiretroviral therapy (HAART) and CD4 lymphocyte response was assessed in a cohort of 249 human immunodeficiency virus (HIV) type 1-infected women at 3 times: 1 before and 2 after initiation of therapy, with follow-up of 6-12 months. Patients with a durable response to HAART (i.e., >1 log decrease in HIV-1 RNA sustained for the study periods) had a continuous and significant increase in CD4 cell counts over time, whereas those with no response (<0.5 log decrease in HIV-1 RNA) had a slight decline. Patients with a mixed response (initial decrease >1 log, followed by a subsequent decrease <0.5 log) had an increase in CD4 cell count, followed by a plateau. The trend in CD4 cell count differed significantly by response to HAART, with those patients who experienced a durable response having significantly higher CD4 cell counts than others.

Acquired Immunodeficiency Syndrome↗

Impact of enoxaparin low molecular weight heparin in patients with Q-wave myocardial infarction.

A subgroup meta-analysis from the Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q-Wave Coronary Events (ESSENCE) and the Thrombolysis in Myocardial Infarction (TIMI) 11B studies has shown that enoxaparin is superior to unfractionated heparin in reducing the composite end points of death, myocardial infarction, and emergency revascularization in patients with Q-wave myocardial infarction. The beneficial treatment effect was significant at 43 days.

Aged↗

The TIMI risk score for unstable angina/non-ST elevation MI: A method for prognostication and therapeutic decision making.

CONTEXT: Patients with unstable angina/non-ST-segment elevation myocardial infarction (MI) (UA/NSTEMI) present with a wide spectrum of risk for death and cardiac ischemic events. OBJECTIVE: To develop a simple risk score that has broad applicability, is easily calculated at patient presentation, does not require a computer, and identifies patients with different responses to treatments for UA/NSTEMI. DESIGN, SETTING, AND PATIENTS: Two phase 3, international, randomized, double-blind trials (the Thrombolysis in Myocardial Infarction [TIMI] 11B trial [August 1996-March 1998] and the Efficacy and Safety of Subcutaneous Enoxaparin in Unstable Angina and Non-Q-Wave MI trial [ESSENCE; October 1994-May 1996]). A total of 1957 patients with UA/NSTEMI were assigned to receive unfractionated heparin (test cohort) and 1953 to receive enoxaparin in TIMI 11B; 1564 and 1607 were assigned respectively in ESSENCE. The 3 validation cohorts were the unfractionated heparin group from ESSENCE and both enoxaparin groups. MAIN OUTCOME MEASURES: The TIMI risk score was derived in the test cohort by selection of independent prognostic variables using multivariate logistic regression, assignment of value of 1 when a factor was present and 0 when it was absent, and summing the number of factors present to categorize patients into risk strata. Relative differences in response to therapeutic interventions were determined by comparing the slopes of the rates of events with increasing score in treatment groups and by testing for an interaction between risk score and treatment. Outcomes were TIMI risk score for developing at least 1 component of the primary end point (all-cause mortality, new or recurrent MI, or severe recurrent ischemia requiring urgent revascularization) through 14 days after randomization. RESULTS: The 7 TIMI risk score predictor variables were age 65 years or older, at least 3 risk factors for coronary artery disease, prior coronary stenosis of 50% or more, ST-segment deviation on electrocardiogram at presentation, at least 2 anginal events in prior 24 hours, use of aspirin in prior 7 days, and elevated serum cardiac markers. Event rates increased significantly as the TIMI risk score increased in the test cohort in TIMI 11B: 4.7% for a score of 0/1; 8.3% for 2; 13. 2% for 3; 19.9% for 4; 26.2% for 5; and 40.9% for 6/7 (P<.001 by chi(2) for trend). The pattern of increasing event rates with increasing TIMI risk score was confirmed in all 3 validation groups (P<.001). The slope of the increase in event rates with increasing numbers of risk factors was significantly lower in the enoxaparin groups in both TIMI 11B (P =.01) and ESSENCE (P =.03) and there was a significant interaction between TIMI risk score and treatment (P =. 02). CONCLUSIONS: In patients with UA/NSTEMI, the TIMI risk score is a simple prognostication scheme that categorizes a patient's risk of death and ischemic events and provides a basis for therapeutic decision making. JAMA. 2000;284:835-842

Aged↗

Factors associated with incident self-reported AIDS among women enrolled in the women's interagency HIV study (WIHS). WIHS Collaboratorive Study Group.

We evaluated factors associated with incident self-reported AIDS diagnoses among HIV-infected women in the Women's Interagency HIV Study (WIHS). Baseline information included age, race/ethnicity, HIV risk category, site of enrollment, years of education, cigarette smoking, CD4 cell count, and HIV viral load. Baseline and follow-up data on self-reported AIDS were analyzed using chi-square, Kaplan-Meier, and Cox proportional hazard models. Among the 1397 HIV-infected women who reported being free of clinical AIDS at baseline, 335 women (24%) reported an incident AIDS diagnosis during follow-up. In stratified Kaplan-Meier analyses, the development of self-reported AIDS was significantly associated with baseline CD4 cell count and viral load (p<0.01). In multivariate Cox proportional hazard analyses, women were statistically more likely to report AIDS if they had CD4 cell counts below 195 cells/mm3 (p<0.01), HIV RNA >4000 copies/ml (p<0.01), were current smokers (p<0.01), and had "no identifiable risk" for acquisition of HIV (p = 0.03). Self-reports of a clinical AIDS diagnosis may not always be accurate, but laboratory markers of HIV disease indicate that those women who self-report such diagnoses have greater immunodeficiency and a higher viral load when compared with those who report no AIDS-defining diagnoses.

Acquired Immunodeficiency Syndrome↗

Association of race and gender with HIV-1 RNA levels and immunologic progression.

CONTEXT: HIV-1 RNA and lymphocyte subset levels are the principal indications for antiretroviral treatment. Past reports have differed with regard to the effect of gender and race on these measures and in measures of disease progression. OBJECTIVE: To assess racial and gender differences in HIV-1 RNA levels and CD4+ lymphocyte decline. DESIGN: A longitudinal study based in the two largest HIV natural history cohort studies conducted in 7 metropolitan areas of the United States. RESULTS: In all, 1256 adult women and 1603 adult men for whom multiple data points were available prior to initiation of antiretroviral therapy were included. Women were more likely to be nonwhite, to have a history of injection drug use, and to have HIV-associated symptoms. After adjustment for differences in measurement method, baseline CD4+ cell count, age, and clinical symptoms, HIV-1 RNA levels were 32% to 50% lower in women than in men at CD4+ counts >200 cells/mm3 (p <.001) but not at CD4+ cell counts <200 cells/mm3. HIV-1 RNA levels were also 41% lower in nonwhites than in whites (p <.001) and 21% lower in persons reporting a prior history of injection drug use (p <.001). Women had more rapid declines in CD4+ cell counts over time than men (difference in slope of 46 cells/year) and nonwhite individuals had slower decline in CD4 cell counts than whites (difference of 39 cells/year). CONCLUSIONS: Both race and gender influence the values of HIV-1 RNA and the rate of HIV-1 disease progression as indicated by decline in CD4 cell counts over time. These effects could provide clues regarding the factors that influence HIV-disease progression and may indicate that guidelines for therapy should be adjusted for demographic characteristics.

Acquired Immunodeficiency Syndrome↗

Serum albumin as a predictor of survival in HIV-infected women in the Women's Interagency HIV study.

BACKGROUND: The level of serum albumin is associated with mortality in a wide variety of chronic diseases. However, few studies have examined the relationship between serum albumin and survival in HIV-1 infection. OBJECTIVES: To determine whether the serum albumin level is associated with survival in HIV-1 infected women. DESIGN: Prospective cohort study. Patients were interviewed and examined at 6 month intervals. SETTING: A North American multi-institutional cohort of HIV-infected women from five geographical areas. PARTICIPANTS: A total of 2056 HIV-infected women at various stages of disease. MEASUREMENTS: Mortality during the first 3 years of follow-up. The relative risk of death by serum albumin level was estimated using a proportional hazards ratio adjusted for CD4 cell count, HIV-1-RNA level and other relevant covariates. RESULT: Three year mortality for women in the lowest serum albumin category (< 35 g/l) was 48% compared with 11% in the highest category (> or = 42 g/l; P < 0.001). The adjusted relative hazard (RH) of death was 3.1 times greater for those in the lowest albumin category (P < 0.01). The excess risk associated with lower serum albumin levels remained when subjects with moderate to severe immunosuppression and abnormal kidney and liver function were excluded (P < 0.01). CONCLUSION: The baseline serum albumin level is an independent predictor of mortality in HIV-1-infected women. The serum albumin level may be a useful additional marker of HIV-1 disease progression, particularly among asymptomatic women with little or no evidence of immunosuppression.

Adult↗

Effect of HIV infection on menstrual cycle length.

HIV serostatus and menstrual function were examined using prospectively collected menstrual data from 802 HIV-seropositive and 273 HIV-seronegative women, ages 20 to 44, enrolled in two cohort studies of HIV infection in North American women. The associations between HIV serostatus and the probabilities of having a cycle lasting >40 days (n = 541 cycles), >90 days (n = 67 cycles), <18 days (n = 316 cycles) and mean length and variability of 18 to 40 day cycles (n = 3,634) were assessed. After adjustment for demographic characteristics, body mass index, and substance use, seropositivity increased the odds of having a very short cycle (< 18 days, odds ratio [OR], 1.45; 95% confidence interval [CI], 1.00-2.11) and a very long cycle (>90 days, OR, 1.32; 95% CI, 0.68-2.58) slightly, although the latter CIs include one. Seropositivity did not increase the odds of having a moderately long cycle (>40 days, OR, 1.14) or affect mean cycle length or variability (beta, 0.30 +/- 0.20; between-woman standard deviation [SD], 2.2 days [HIV-seronegative] and 1.9 days [HIV-seropositive]; within-woman SD, 3.5 days for both). Although seropositivity may slightly increase the probability of very short cycles, HIV serostatus has little overall effect on amenorrhea, menstrual cycle length, or variability. Among HIV-seropositive women, higher viral loads and lower CD4+ counts were associated with increased cycle variability and polymenorrhea.

Adult↗

Marked declines in human immunodeficiency virus-related mortality in Chicago in women, African Americans, Hispanics, young adults, and injection drug users, from 1995 through 1997.

BACKGROUND: Declines in human immunodeficiency virus (HIV)-related mortality between 1995 and 1996 were seen across the United States but were small to nonexistent among people in marginalized sectors who are most likely to contract HIV and die of its effects. No comprehensive analysis describing HIV-related mortality in 1997 was available. OBJECTIVE: To describe Chicago's HIV-related mortality trends up to and including 1997, with specific attention focused on marginalized populations. METHODS: An analysis of cross-sectional HIV-related mortality data with emphasis on the years 1995 through 1997 was conducted for Chicago, Ill. Numbers, proportions, and rates of declines in HIV-related deaths were examined for the city as a whole and also among those diagnosed at Cook County Hospital, as a proxy for people with very low socioeconomic status. RESULTS: Between 1995 and 1996 there was an overall decline of 19% in HIV-related mortality in Chicago but small or no declines among women, African Americans, Hispanics, injection drug users, and people aged 20 to 29 years and more than 50 years. Between 1995 and 1997 there was an overall decline of 61%. At that time the declines were spread more evenly across diverse groups. There were almost no significant differences between the declines for these groups at Cook County Hospital and in the rest of Chicago. CONCLUSIONS: The HIV-related mortality has fallen dramatically in Chicago since 1995, the year of its maximum. During 1997, declines were seen among all groups. Declines were also seen among the most disenfranchised of the city. Access to care and the new combination therapies are apparently sustaining life for many in Chicago.

Adult↗

Risk of cardiovascular disease measured by carotid intima-media thickness at age 49-51: lifecourse study.

OBJECTIVE: To quantify the direct and indirect effects of fetal life, childhood, and adult life on risk of cardiovascular disease at age 49-51 years. DESIGN: Follow up study of the "Newcastle thousand families" birth cohort established in 1947. PARTICIPANTS: 154 men and 193 women who completed a health and lifestyle questionnaire and attended for clinical examination between October 1996 and December 1998. MAIN OUTCOME MEASURES: Correlations between mean intima-media thickness of the carotid artery (carotid intima-media thickness) and family history, birth weight, and socioeconomic position around birth; socioeconomic position, growth, illness, and adverse life events in childhood; and adult socioeconomic position, lifestyle, and biological risk markers. Proportions of variance in carotid intima-media thickness that were accounted for by each stage of the lifecourse. RESULTS: Socioeconomic position at birth and birth weight were negatively associated with carotid intima-media thickness, although only social class at birth in women was a statistically significant covariate independent of adult lifestyle. These early life variables accounted directly for 2.2% of total variance in men and 2.0% in women. More variation in carotid intima-media thickness was explained by adult socioeconomic position and lifestyle, which accounted directly and indirectly for 3.4% of variance in men (95% confidence interval 0.5% to 6.2%) and 7.6% in women (2.1% to 13.0%). Biological risk markers measured in adulthood independently accounted for a further 9.5% of variance in men (2.4% to 14.2%) and 4.9% in women (1.6% to 7.4%). CONCLUSIONS: Adult lifestyle and biological risk markers were the most important determinants of the cardiovascular health of the study members of the Newcastle thousand families cohort at age 49-51 years. The limited overall effect of early life factors may reflect the postwar birth year of this cohort.

Cardiovascular Diseases↗

[Carcinoma of the cecum presenting as intussusception].

In intussusception a proximal bowel segment (intussusceptum) invaginates into the lumen of a distal bowel segment (intussuscipiens). In adults intussusception represents a rare cause of intestinal obstruction and is usually secondary to an identifiable lesion that requires surgical treatment other than that of the intussusception itself. We present a 57-year-old woman with metastatic colonic carcinoma of the ileocecal valve and intussusception of the ileum into the cecum. Right hemicolectomy was performed.

Adult↗

Human dural replacement with acellular dermis: clinical results and a review of the literature.

BACKGROUND: The search for the ideal dural replacement in the setting where autogenous tissues are unavailable or inadequate still persists. Because of the ability of acellular dermis (AlloDerm, LifeCell Corporation, The Woodlands, TX) to remodel itself into native tissue, this dynamic quality is hypothesized to occur when used as a dural replacement. METHODS: We report the long-term outcome of a small cohort of patients who, to our knowledge, were the first patients to receive AlloDerm for dural replacement. In addition, to put these current findings in a historical perspective, we present a review of the literature for dural replacement. RESULTS: Ten patients all successfully underwent duraplasty with AlloDerm with only one postoperative complication that was not related to the acellular dermal dural repair. CONCLUSIONS: We contend that AlloDerm is a safe and viable option for dural replacement in cases in which autogenous tissues are either unavailable or insufficient for proper reconstruction.

Adult↗

Review: nuclear lamins--structural proteins with fundamental functions.

The nuclear lamina is located between the inner nuclear membrane and the peripheral chromatin. It is composed of both peripheral and integral membrane proteins, including lamins and lamina-associated proteins. Lamins can interact with one another, with lamina-associated proteins, with nuclear scaffold proteins, and with chromatin. Likewise, most of the lamina-associated proteins are likely to interact directly with chromatin. The nuclear lamina is required for proper cell cycle regulation, chromatin organization, DNA replication, cell differentiation, and apoptosis. Mutations in proteins of the nuclear lamina can disrupt these activities and cause genetic diseases. The structure and assembly of the nuclear lamina proteins and their roles in chromatin organization and cell cycle regulation were recently reviewed. In this review, we discuss the roles of the nuclear lamina in DNA replication and apoptosis and analyze how mutations in nuclear lamina proteins might cause genetic diseases.

Animals↗

Inadequate preanesthesia equipment checks in a simulator.

PURPOSE: To assess how completely anesthesiologists check their machinery and equipment before use, and to determine what influence seniority, age and type of practice may have on checking practices. METHODS: One hundred and twenty anesthesiologists were videotaped during a simulated anesthesia session. Each participant was scored by an assessor according to the number of items checked prior to the induction of anesthesia. A checklist of 20 items derived from well-publicized, international standards was used. RESULTS: Participants were grouped according to their type of practice. Overall, mean scores were low. The ideal score was 20. There were no differences among university anesthesiologists (mean score 10.1, standard deviation 4.3), community anesthesiologists (7.5 +/- 4.3) and anesthesia residents (9.0 +/- 3.8). Each of these groups scored, on average, better than medical students (3.6 +/- 3.7) (P < 0.05). Neither age (r = 0.15, P > 0.1) nor number of years in practice (r = -0.18, P > 0.1) correlated with score. CONCLUSIONS: Our study suggests that the equipment-checking practices of anesthesiologists require considerable improvement when compared with national and international standards. Possible reasons for this are discussed and some remedial suggestions are made.

Anesthesiology↗