Antibodies to cardiac tissue in acute ischemic heart disease

Serially collected sera of 117 patients with acute ischemic heart disease were studied for the presence of antibodies to cardiac tissue by the passive hemagglutination technic. The average titer of these antibodies in 71 patients with acute myocardial infarction increased severalfold from admission to a peak after two to four weeks of hospitalization, and then declined. Sera of 46 patients with acute coronary insufficiency showed on the average a less pronounced rise and an earlier peak.

Of 50 patients with acute myocardial infarction, 23 (46%) showed a fourfold or more increase in titer during the first month, while of the 33 patients with acute coronary insufficiency, 14 (42%) showed a similar rise. Maximum titers of 80 or higher were found in 20 of the 50 patients (40%) with acute myocardial infarction and 9 of 33 patients (27%) with acute coronary insufficiency. Many patients showed low titers at all times.

Only 1 patient in the series had clinical features suggesting the postmyocardial infarction syndrome. He had high titers during the acute stage of his infarct, but no sera were obtained during the convalescent period. The postmyocardial infarction syndrome did not develop in any of the 11 patients who had titers of 80 beyond the first month.

The observation of the development of circulating antibodies to cardiac tissue in acute ischemic heart disease does not in itself permit conclusions regarding the pathogenetic significance of such antibodies.     

Alterations in very low density lipoprotein subfractions in normotriglyceridemic non-insulin-dependent diabetics.

Lipid and apoprotein composition of four very low density lipoprotein (VLDL) subfractions decreasing in Sf value were evaluated in the fasting state in 12 normolipidemic Pima Indians (6 M, 6 F, age 39 +/- 1.7 yrs) (mean +/- SEM) with non-insulin-dependent diabetes mellitus (NIDDM) in poor glycemic control (HbA1 9.8 +/- 2.9%) and in 14 normoglycemic Pima controls matched for age, BMI and lipid values. Total cholesterol (CHOL), triglyceride (TG), phospholipids (PL), total protein (TP), apo B, apo CII, apo CIII and apoE were assayed in total VLDL and in each of the four VLDL subfractions designed as A (Sf greater than 400), B (Sf 175-400), C (Sf 100-175), and D (Sf 20-100). Diabetics compared to nondiabetics had higher concentrations of all constituents of VLDL D, with the largest changes being in TG (38.0 +/- 3.8 vs 28.0 +/- 2.5 mg/dl, P less than 0.04), PL (14.0 +/- 1.3 vs 10.0 +/- 1.0 mg/dl, P less than 0.04), TP (9.8 +/- 0.8 vs 7.6 +/- 2.4 mg/dl, P less than 0.05), apo B (6.3 +/- 0.5 vs 4.7 +/- 0.4 mg/dl, P less than 0.03) and apoE (0.73 +/- 0.09 vs 0.52 +/- 0.04 mg/dl, P less than 0.04). Since no difference was found between the groups in percentage composition of lipids or apoproteins in total VLDL and in all VLDL subfractions, the data suggest that in diabetics, even when normolipidemic, there is an increase in the number rather than in the composition of the smallest VLDL subfraction (VLDL D), which are usually considered to be more atherogenic.     

Alloimmunization to platelets in heavily transfused patients with sickle cell disease

Bone marrow transplantation (BMT) is now an option for some patients with sickle cell disease (SCD). Many SCD patients are multiply transfused with red blood cells (RBCs), and may be immunized to alloantigens other than erythrocyte antigens. Because platelet refractoriness is a significant complication during BMT, we wished to determine the prevalence of alloimmunization to platelets in transfused SCD patients. Sera collected from 47 transfused and 14 untransfused SCD patients were screened for HLA and platelet-specific antibodies. Transfusion and RBC antibody histories were reviewed. A subset of the patients were rescreened 1 year later. Eighty-five percent of patients with at least 50 RBC transfusions (22 of 26), 48% of patients with less than 50 transfusions (10 of 21), and none of 14 untransfused patients demonstrated platelet alloimmunization (P < .05). Platelet alloimmunization was more prevalent than RBC alloimmunization (20% to 30%). Half of the platelet reactivity was chloroquine-elutable. Eighteen of 22 patients (82%) on chronic RBC transfusion remained platelet-alloimmunized 11 to 22 months after initial testing. In summary, 85% of heavily transfused SCD patients are alloimmunized to HLA and/or platelet-specific antigens. These patients may be refractory to platelet transfusion, a condition that would increase their risk during BMT. Leukodepletion in the transfusion support of SCD patients should be considered to prevent platelet alloimmunization.     

Microsomal acetyl-CoA carboxylase: evidence for association of enzyme polymer with liver microsomes.

Fatty acid synthesis is traditionally viewed as being confined to the cytosolic cellular fraction, although a substantial body of data indicates that both microsomes and mitochondria are capable of initiating fatty acid synthesis and may contain acetyl-CoA carboxylase [acetyl-CoA:carbon-doxide ligase (ADP-forming), EC 6.4.1.2], fatty acid synthetase, and ATP-citrate lyase [ATP citrate (pro-3S)-lyase; ATP:citrate oxaloacetate-lyase (pro-3S-CH2COO- leads to acetyl-CoA; ATP-dephosphorylating), EC 4.1.3.8] activities. We have identified 32P-labeled acetyl-CoA carboxylase and 32P-labeled ATP-citrate lyase by immunoprecipitation of a rat hepatocyte microsomal preparation. In the transition between the fasting state (low rates of lipogenesis) and fasting/re-feeding (high rates), the fraction of total cytosolic plus microsomal acetyl-CoA carboxylase in the microsomes increases from 6% to 43%, whereas the microsomal proportion of total fatty acid synthetase and ATP-citrate lyase remains approximately 10%. Microsome isolation conditions favoring carboxylase polymerization (presence of citrate) promote microsomal association, whereas conditions favoring enzyme protomerization (malonyl-CoA, preincubation with cyclic AMP/ATP/Mg2+) diminish this association. The microsomal enzyme has a 5-fold higher specific activity than the cytosolic enzyme as determined by immunotitration. Sucrose density gradient analysis of the microsomal fraction indicates that a substantial portion of carboxylase activity sediments with marker enzymes for endoplasmic reticulum, plasma membrane, Golgi apparatus, and outer mitochondrial membrane, while cytosolic enzyme or isolated enzyme incubated under polymerizing conditions does not penetrate the gradient. These data suggest that the microsomes may be a significant locus of fatty acid synthesis initiated with association of acetyl-CoA carboxylase polymer with this fraction.     

Drug scene roles and HIV risk

Aims. Drug scenes (social and spatial drug-using and drug-selling environments) have complex role structures. Many drug injectors earn money or drugs as drug or syringe sellers, hit doctors (people who help others to inject) commercial sex workers, or in other roles. This paper aims to measure "role behaviors" of drug injectors; describe which drug injectors are more likely to engage in such role behaviors; and to determine whether roles are related to elements of HIV risk . Design. Cross-sectional study of drug injectors . Setting. Bushwick, a section of Brooklyn, New York, a major location for injection drug use and drug sales . Participants. Seven hundred and sixty-seven street-recruited drug injectors . Measurements. Participants were interviewed about their roles, behaviors, socio-demographics and risk networks; sera were collected and assayed for HIV and hepatitis B core antibody . Findings. Socio-demographic variables are related to role-holding in complex ways. Economic need is generally associated with engaging in drug-scene role behaviors. Holders of these roles are at greater behavioral and network risk for HIV and other blood-borne infections than are other drug injectors. They also engage in extensive communication with other drug users, including discussion of HIV risk reduction . Conclusion. Role behaviors can be measured in quantitative studies, and seem to be related to HIV risk. Role-holders may be strategic targets for risk-reduction campaigns. It seems feasible and advisable to measure drug scene role-holding in research on drug users.     

Health-related quality of life predicts future health care utilization and mortality in veterans with self-reported physician-diagnosed arthritis: the veterans arthritis quality of life study

OBJECTIVE: To investigate whether health-related quality of life (HRQOL) measures predict health care utilization and mortality in a cohort of veterans with self-reported physician-diagnosed arthritis. METHODS: A cohort of veterans from the Upper Midwest Veterans Integrated Service Network (VISN) was mailed a self-administered questionnaire that was composed of the SF-36V (modified from SF-36 for use in veterans) and questions regarding demographics, current smoking status, limitation of activities of daily living (ADLs), and preexisting physician-diagnosed medical conditions, including arthritis. Within subjects reporting physician-diagnosed arthritis, we analyzed the associations between the SF-36V component summary scales (physical and mental component summary, PCS and MCS, respectively) and the occurrence of any hospitalization, number of hospitalizations, number of outpatient visits, and mortality, for the year after survey administration, using multivariable regression analyses. RESULTS: Of 34,440 survey responders who answered a question regarding arthritis, 18,464 (58%) subjects reported physician-diagnosed arthritis. Arthritic patients in the lowest tertile of PCS scores had significantly higher odds of any hospitalization (Odds ratio (OR) 1.49, 95% confidence interval (CI) [1.25-1.76]) and mortality (OR 1.69, 95% CI [1.18-2.42]), and a significantly higher number of hospitalizations/year (Rate ratio (RR) 1.09, 95% CI [1.05-1.13]) and outpatient visits/year (RR 1.07, 95% CI [1.03-1.11]). Arthritic patients in the lowest tertile of MCS scores had significantly higher odds of any hospitalization (OR 1.20, 95% CI [1.02-1.41]), mortality (OR 2.14, 95% CI [1.56-2.94]), and a significantly higher number of hospitalizations/year (RR 1.05, 95% CI [1.02-1.09]) and outpatient visits/year (RR 1.07, 95% CI [1.03-1.11]). CONCLUSIONS: HRQOL, as assessed by the SF-36V, predicts future inpatient and outpatient health care utilization and mortality in veterans with self-report of physician-diagnosed arthritis.     

Comparison of effects on low-density lipoprotein cholesterol and high-density lipoprotein cholesterol with rosuvastatin versus atorvastatin in patients with type IIa or IIb hypercholesterolemia.

This randomized, double-blind, placebo-controlled trial was conducted in 52 centers in North America to compare the effects of the new, highly effective statin, rosuvastatin, with atorvastatin and placebo in hypercholesterolemic patients. After a 6-week dietary run-in, 516 patients with low-density lipoprotein (LDL) cholesterol > or =4.14 mmol/L (160 mg/dl) and < 6.47 mmol/L (250 mg/dl) and triglycerides < or =4.52 mmol/L (400 mg/dl) were randomized to 12 weeks of once-daily placebo (n = 132), rosuvastatin 5 mg (n = 128), rosuvastatin 10 mg (n = 129), or atorvastatin 10 mg (n = 127). The primary efficacy end point was percent change in LDL cholesterol. Secondary efficacy variables were achievement of National Cholesterol Education Program (NCEP) Adult Treatment Panel II (ATP II), ATP III, and European Atherosclerosis Society LDL cholesterol goals and percent change from baseline in high-density lipoprotein (HDL) cholesterol, total cholesterol, triglycerides, non-HDL cholesterol, apolipoprotein B, and apolipoprotein A-I. Rosuvastatin 5 and 10 mg compared with atorvastatin 10 mg were associated with greater LDL cholesterol reductions (-40% and -43% vs 35%; p <0.01 and p <0.001, respectively) and HDL cholesterol increases (13% and 12% vs 8%, p <0.01 and p <0.05, respectively). Total cholesterol and apolipoprotein B reductions and apolipoprotein A-I increases were also greater with rosuvastatin; triglyceride reductions were similar. Rosuvastatin 5 and 10 mg were associated with improved achievement in ATP II (84% in both rosuvastatin groups vs 73%) and ATP III (84% and 82% vs 72%) LDL cholesterol goals, and rosuvastatin 10 mg was more effective than atorvastatin in achieving European Atherosclerosis Society LDL cholesterol goals. Both treatments were well tolerated.