A blinded, randomized, multicenter study of an intravenous Staphylococcus aureus immune globulin.

OBJECTIVES: Very low birth weight (VLBW) infants are vulnerable to nosocomial infections and subsequent morbidity; including infections caused by Staphylococcus aureus: 85% of nosocomial S. aureus infections are caused by capsular polysaccharide (CPS) types 5 and 8. Altastaph is a polyclonal investigational human immunoglobulin G (IgG) with high levels of opsonizing S. aureus CPS types 5 and 8 IgG. METHODS: A Phase 2 clinical trial to assess the safety and kinetics of Altastaph in VLBW infants. Neonates in this multicenter study were randomized to receive two identical 20 ml/kg i.v. infusions of either 0.45% NaCl placebo or 1000 mg Altastaph/kg. Each infant was followed for 28 days after the second infusion or until discharge. Serum S. aureus CPS types 5 and 8 IgG levels were measured preinfusion and at various times after each infusion. RESULTS: Of 206 neonates, 158 received both infusions. Adverse events were similar in the two treatment groups. Six subjects (3% in each group) discontinued owing to an adverse event. Geometric mean anti-type 5 IgG levels were 402 and 642 mcg/ml 1 day following infusion of the first (day 0) and Second (day 14) doses, respectively, in neonates < or =1000 g and slightly higher in neonates 1001 to 1500 g. Trough levels before second infusion were 188 mcg/ml. Type 8 IgG levels were similar. Geometric mean IgG levels among placebo recipients were consistently <2 and <5 mcg/ml for types 5 and 8 in both weight groups. Three episodes of S. aureus bacteremia occurred in each arm. CONCLUSIONS: Infusion of Altastaph in VLBW neonates resulted in high levels of specific S. aureus types 5 and 8 CPS IgG. The administration of this anti-staphylococcal hyperimmune globulin was well tolerated in this population.     

Pyretic action of low doses of gamma-hydroxybutyrate in rats

gamma-Hydroxybutyrate (GHB) has been found to have a biphasic effect on body temperature with increased body temperature after low doses (5-10 mg/kg) and decreased body temperature after high doses (300-500 mg/kg). Brain levels of GHB between 30 and 60 min post-injection of GHB were not altered by the low doses (5-10 mg/kg), although a dose of 200 mg/kg produced a large increase in the brain concentration.     

Basic sciences in problem-based learning and conventional curricula: students' attitudes

The purpose of this study was to compare the attitudes toward basic sciences of students in a preclinical problem-based curriculum and a conventional lecture-based curriculum at the end of their second year of medical school. The results showed that the PBL class had more positive attitudes toward basic sciences than students in the conventional class. These results may reflect a learning environment where students meet many scientist role models as teachers and where basic science is learnt in the context of clinical problems.     

Optic disk neovascularization and retinal vessel diameter in diabetic retinopathy

We measured retinal vessel diameter before and after panretinal photocoagulation in 59 eyes with diabetic retinopathy and moderate to severe optic disk neovascularization. Treatment significantly reduced mean arteriolar and venular diameter. The diameter of the retinal arterioles after treatment correlated significantly with the amount of regression in disk neovascularization. Eyes with large diameter vessels after treatment usually had little or no regression of proliferative retinopathy, whereas regression was more frequently seen in eyes with smaller diameter vessels after treatment.     

Propagation of alloreactive lymphocytes from histologically negative endomyocardial biopsies from heart transplant patients. Association with subsequent histological evidence of allograft rejection

Endomyocardial biopsies from heart transplant patients were cultured in vitro in the presence of Interleukin-2 and irradiated feeder cells to propagate graft-infiltrating lymphocytes. A correlation was seen between the frequency of lymphocyte growth and the degree of cellular infiltration of the biopsies. In this study, 43 of 113 (38%) histologically negative biopsies obtained from 55 patients during the first month post-transplant yielded lymphocyte cultures. The cumulative incidence of subsequent histological rejection was considerably higher in patients with such "grower" biopsies than in patients with "nongrower" biopsies. In the grower group, we were able to obtain data on alloreactivity of 32 lymphocyte cultures assayed by primed lymphocyte testing (PLT). The presence of donor-specific PLT reactivity in the cultured lymphocytes was associated with an additional risk for subsequent histological rejection. These findings suggest that the in vitro culturing of histologically negative endomyocardial biopsies will identify patients at increased risk for developing heart transplant rejection.     

Pythium insidiosum sp. nov., the etiologic agent of pythiosis.

Pythium insidiosum sp. nov., the etiologic agent of pythiosis, a cosmopolitan disease of horses, cattle, and dogs, is described and illustrated.     

The risk of myocardial infarction after quitting smoking in men under 55 years of age

We assessed the effect of quitting cigarette smoking on the incidence of nonfatal myocardial infarction in men under the age of 55 in a case-control study of 1873 men with first episodes of myocardial infarction and 2775 controls. For "current" smokers (men who had smoked in the previous year) as compared with those who had never smoked, the estimated relative risk of myocardial infarction, adjusted for age, was 2.9 (95 per cent confidence interval, 2.4 to 3.4). Among exsmokers (those who had last smoked at least one year previously), the relative-risk estimate declined to a value close to unity for those who had abstained for at least two years; the estimate was 2.0 (1.1 to 3.8) for men who had abstained for 12 to 23 months, and the estimates were about 1.0 for men who had abstained for longer intervals. The results were unchanged by allowance for multiple potential confounding factors. A similar pattern was apparent among exsmokers who had smoked heavily for many years; among those predisposed to a myocardial infarction because of family history, hypertension, or other risk factors; and among those with no apparent predisposition. The results suggest that the risk of myocardial infarction in cigarette smokers decreases within a few years of quitting to a level similar to that in men who have never smoked.     

Immunodiffusion test for serodiagnosing subcutaneous zygomycosis.

Culture filtrate antigens of Basidiobolus ranarum and Conidiobolus coronatus were analyzed by immunodiffusion (ID) with homologous rabbit antisera. B. ranarum and C. coronatus were each found to have five specific antigens. Results of tests with heterologous antisera indicated that all of the species shared at least one antigen. ID tests incorporating the specific precipitin bands as references were developed for detection of basidiobolomycosis and conidiobolomycosis. These tests were performed with sera from humans and horses with proven basidiobolomycosis and conidiobolomycosis as well as with control sera from humans and animals with and without heterologous mycotic and oomycotic infections. Only sera from cases of basidiobolomycosis and conidiobolomycosis produced lines of identity with the reference precipitates of B. ranarum and C. coronatus, respectively. The ID tests were found to be completely sensitive and specific for determining the etiology of zygomycosis caused by these two species. In addition they appeared useful for monitoring resolution of the infections.     

Risk of localized and widespread endometrial cancer in relation to recent and discontinued use of conjugated estrogens

In a case-control study of the risk of adenocarcinoma of the endometrium in relation to conjugated-estrogen use, we found that 31 per cent of 425 women with endometrial cancer and 15 per cent of 792 controls reported having used conjugated estrogens; the rate-ratio estimate was 3.5 with a 95 per cent confidence interval of 2.6 to 4.7. For use that lasted at least one year, the rate-ratio estimate for Stage I or II cancer was 5.2 (95 per cent confidence interval, 3.7 to 7.2), and for Stages III and IV combined it was 3.1 (1.5 to 6.4). Among women who had used estrogen for at least one year and then discontinued it, the risk of endometrial cancer remained significantly elevated even after estrogen-free intervals of over 10 years. The findings suggest that long-term use of conjugated estrogen increases the risk of both localized and widespread endometrial cancer. The data also suggest that women who have taken conjugated estrogen for one or more years remain at increased risk for at least 10 years after they discontinue use. Such women should be considered for long-term gynecologic surveillance.