Showing papers by "Marc A. Pfeffer published in 2000"

Elevation of Tumor Necrosis Factor-α and Increased Risk of Recurrent Coronary Events After Myocardial Infarction

Abstract: Background—Levels of tumor necrosis factor-α (TNF-α) increase with acute ischemia. However, whether elevations of TNF-α in the stable phase after myocardial ischemia (MI) are associated with increa...

VLDL, apolipoproteins B, CIII, and E, and risk of recurrent coronary events in the cholesterol and recurrent events (CARE) trial

Abstract: Background—Plasma triglyceride concentration has been an inconsistent independent risk factor for coronary heart disease, perhaps because of the metabolic heterogeneity among VLDL particles, the main carriers of triglycerides in plasma. Methods and Results—We conducted a prospective, nested case-control study in the Cholesterol and Recurrent Events (CARE) trial, a randomized placebo-controlled trial of pravastatin in 4159 patients with myocardial infarction and average LDL concentrations at baseline (115 to 174 mg/dL, mean 139 mg/dL). Baseline concentrations of VLDL–apolipoprotein (apo) B (the VLDL particle concentration), VLDL lipids, and apoCIII and apoE in VLDL+LDL and in HDL were compared in patients who had either a myocardial infarction or coronary death (cases, n=418) with those in patients who did not have a cardiovascular event (control subjects, n=370) in 5 years of follow-up. VLDL-cholesterol, VLDL-triglyceride, VLDL-apoB, apoCIII and apoE in VLDL+LDL and apoE in HDL were all interrelated, and ...

Impairment in quality of life among patients seeking surgery for hyperhidrosis (excessive sweating): preliminary results.

Abstract: Background The present paper describes the initial stages of the development and administration of a short, disease-specific, health related questionnaire to assess the impact of suffering from hyperhidrosis (excessive sweating) on the Quality of Life (QoL) of patients who are anticipating surgery for this disorder. Method The study was performed in two stages: 1. The life domains in which the condition impairs QoL were assessed by in-depth interviews with 10 patients suffering from hyperhidrosis. 2. A questionnaire covering five life domains was built based on these interviews. 3. This questionnaire was administered to 48 patients, 30 females and 18 males between the ages 15 and 48. Results Results showed that subjective QoL was significantly lower among females in four of the five life areas and that duration of the condition correlates with a lower quality of life. A regression analysis showed that the subjective suffering of the patients was explained mainly by social aspects. Conclusions The questionnaire is a novel attempt to assess QoL in a disorder with strong esthetic and social consequences and could improve communication between patients and their physicians.

Endothelin-A receptor antagonism during acute myocardial infarction in rats.

Abstract: Endothelin levels are increased in rats with experimentally induced myocardial infarction. The purpose of this study was to determine whether endothelin-A (ETA) receptor antagonism alters ventricular remodeling and the development of heart failure after myocardial infarction (MI). We administered 10 mg/kg/day of A-127722 to rats post-MI for 6 weeks. A hemodynamic study was performed and passive pressure-volume curves obtained. In rats without infarcts, ETA receptor antagonist (n=8; vehicle, n = 5) had no effect. However, in rats with infarcts ETA antagonism (n = 14, MI = 35%; vehicle: n = 19, MI = 32%) reduced systemic arterial and LV systolic (but not end-diastolic) pressures and shifted the pressure-volume relationship to the right. Because LV mass was not changed, the volume-to-mass ratio was increased and was correlated inversely with the ability of the LV to maximally develop pressure. This increase in volume at low distending pressures was also coupled with a tendency (P < 0.06) for reduced scar thickness, suggesting that early initiation of an ETA receptor antagonism increased infarct expansion. The reduction in blood pressure offset the increase in volume such that wall stresses were unchanged, as was LV mass. The early use of ETA receptor antagonism in the rat model of myocardial infarction did not beneficially alter LV remodeling.

Mousepox resulting from use of ectromelia virus-contaminated, imported mouse serum.

Abstract: Mousepox was identified in a single mouse-holding room in early 1999 after a group of 20 CAF1/Hsd mice were inoculated SC with a killed murine spindle cell tumor line, S1509A. The cell line had been used without complications multiple times and was determined to be free of viral contamination on the basis of results of mouse antibody production testing. Of the 20 mice inoculated, 12 mice died by postinoculation day 8. Severe lymphoid and hepatic necrosis was observed in select mice subjected to histologic examination. Ballooning degeneration of epithelial cells with intracytoplasmic eosinophilic inclusion bodies was observed in the skin overlying the inoculation site of the single mouse from which this tissue site was evaluated. Presence of ectromelia virus was confirmed by use of immunohistochemical and polymerase chain reaction analyses, and the virus was isolated after serum, pooled from 5 of the index cases, was inoculated into an immune-naive mouse. Investigation into the source of virus contamination included inoculating mice with aliquots of various S1509A freeze dates; chemically defined media and supplements, including fetal bovine serum; and two lots of pooled commercial mouse sera, after heat inactivation at 56 degrees C for 30 minutes used as a medium supplement. One lot of pooled commercial mouse serum was identified as the source of ectromelia virus. This lot of serum was inadvertently used to feed S1509A cells that were subsequently inoculated into mice. We determined that the contaminated serum, which was purchased in late 1998, originated from China. The serum was imported into the United States as a batch of 43 L in early 1995. The serum was blended into a single lot and filtered (0.2 microm) before distribution to major suppliers throughout the country. The serum was sold or further processed to obtain a variety of serum-derived products. Because murine serum is generally sold in small aliquots (10 to 50 ml), we speculate that several thousand aliquots may have been derived from this batch of serum and, if inoculated into mice, would likely result in additional mousepox outbreaks.

Candesartan in Heart Failure - Assessment of Reduction in Mortality and Morbidity (CHARM) Study Programme.

Abstract: Heart failure is a major cause of death, hospital admissions and poor quality of life. It affects some 1-2% of the general population, increasing to up to 8% in people over 75 years of age. Although treatment with angiotensin-converting enzyme (ACE) inhibitors reduces symptoms and mortality, 50-70% of patients with heart failure still die within 5 years of diagnosis. There is thus clear scope for improving the treatment of patients with this condition. The CHARM programme is designed to define the clinical benefits of the long-acting angiotensin II type 1 (AT 1 ) receptor blocker, candesartan cilexetil, in a wide variety of patients with symptomatic heart failure. Candesartan cilexetil will be evaluated in three double-blind, randomized studies involving patients grouped according to left ventricular function and ACE inhibitor tolerance/intolerance.

Will more complete inhibition of the RAAS with angiotensin receptor blockade improve survival following myocardial infarction

Abstract: Angiotensin-converting enzyme (ACE) inhibitors have a well-established role in the management of patients with hypertension, diabetes, heart failure and myocardial infarction (MI). ACE inhibitors have been particularly well studied in acute and chronic MI with consistent and substantial survival benefits demonstrated, particularly in the higher risk groups. The recent development of angiotensin II (Ang II) receptor blockers (ARBs) as a well tolerated pharmacological therapy to more completely inhibit the actions of Ang II at the AT1-receptor level raises questions concerning comparative efficacy with the proven ACE inhibitor experience. Two major trials will provide a direct comparison of ARBs with an ACE inhibitor. The Valsartan in Acute Myocardial Infarction (VALIANT) trial is specifically designed to compare and contrast the ARB, valsartan, used both alone as well as in combination with a proven ACE inhibitor regimen, in a high risk MI population. VALIANT, with its three arms targetting 14,500 patients, is uniquely poised to determine whether the pharmacological advance in the development of ARBs confers additional clinical (survival) value in high risk MI patients.