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.     

Influence of dietary nucleotides on liver structural recovery and hepatocyte binuclearity in cirrhosis induced by thioacetamide.

Intake of thioacetamide in drinking water causes liver cirrhosis in rats, which exhibit many changes similar to human disease. Nucleotides play an important part in major cellular functions, and recent studies suggest that dietary nucleotides may be considered 'semi-essential' nutrients in situations when an inadequate dietary supply may affect the growth of tissues with a rapid turnover rate. The aim of this study was to assess the effect of dietary nucleotides on lesions in thioacetamide-cirrhotic rats, and to calculate the proportion of mono and binucleated hepatocytes in different experimental groups. Rats were given cirrhosis by oral intake of thioacetamide in the drinking water (300 mg/l) for four months. One group was treated with a standard nucleotide free diet, and another group was treated with the same diet supplemented with 250 mg of nucleotides per 100 g of diet for one and two weeks. A striking reduction (mean (SEM)) in the proportion of binucleated cells was seen in thioacetamide-cirrhotic rats (4.8 (1.3) v 21.4 (1.0)), showing a change in the mitotic mechanism in focal lesions. Cirrhotic rats that consumed a semipurified diet supplemented with nucleotides during two weeks showed considerable histological regeneration of the injured liver. These animals had significantly higher proportion of binucleated cells than did animals at the beginning of the recovery period (8.2 (1.2) v 4.8 (1.3)). In the second week of recovery, both types of diet (F = 5.54, p < 0.05) and the previous administration of thioacetamide (F = 142.82, p < 0.001) had significant effects on the percentage of binucleated hepatocytes.     

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.     

Inhibition of catecholamine synthesis depresses behavior of rats in the holeboard and forced swim tests: influence of previous chronic stress.

Catecholaminergic pathways in the brain are activated during stress and are presumably involved in the control of physiological and behavioral changes triggered by stress. When repeatedly stressed, adaptive changes have been observed in catecholaminergic activity in the brain. In the present experiment, it was assessed whether or not chronic exposure to immobilization (IMO) altered the influence of catecholamines on behavior in the holeboard and forced swim test by administering alpha-methyl-p-tyrosine (an inhibitor of catecholamine synthesis). Adult Sprague-Dawley rats were used. Chronic stress amortiguated the inhibitory effect of acute IMO on some but not all behaviors in the two tests. Whereas previous chronic IMO exacerbated the effects of the drug on struggling and immobility in the forced swim test, no change in response to the drug as a consequence of chronic IMO was observed in the holeboard test. The present data suggest that chronic IMO-induced changes in the catecholaminergic control of some behaviors might be related to depression-like states in rats. The actual physiological meaning of these changes and the specific receptors involved remain to be elucidated.     

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.     

Right internal thoracic artery through the transverse sinus in myocardial revascularization

Background. A major concern in evaluating dynamic cardiomyoplasty has been whether the synchronous stimulation of latissimus dorsi muscle is essential for benefit or not. We studied 10 patients to determine the efficacy of the systolic augmentation generated by the synchronous electrical stimulation of the latissimus dorsi muscle.

Methods. Left ventricular ejection fraction, end-systolic and end-diastolic volume indexes, and stroke volume index obtained during resting, peak exercise, and recovery periods (“on” values) were compared with those obtained 1 week after cessation of electrical stimulus (“off” values). Double product and estimated total body oxygen consumption at peak exercise were also calculated and compared.

Results. Higher ejection fractions (0.36 ± 0.07 versus 0.33 ± 0.06 at rest, 0.40 ± 0.07 versus 0.33 ± 0.07 peak exercise, and 0.37 ± 0.06 versus 0.31 ± 0.06 at recovery) and lower end-systolic volume indexes with relatively constant end-diastolic volume indexes were observed with the cardiomyostimulator on. Further, exercise response was better with the cardiomyostimulator on. Double product indirectly reflected better myocardial oxygen supply/demand ratio when on at peak exercise (17 ± 2.2 mm Hg × beats/min × 10⁻³ for on versus 19 ± 2.6 mm Hg × beats/min × 10⁻³ for off). Estimated total body oxygen consumption was improved at peak exercise when the cardiomyostimulator was functional (12 ± 2.7 mL · kg⁻¹ · min⁻¹ versus 11 ± 2.6 mL · kg⁻¹ · min⁻¹).

Conclusions. Current data suggest a true systolic assist during synchronous contractions of the latissimus dorsi muscle. It is thought, therefore, that synchronous electrical stimulation is essential for maximum benefit and all the beneficial effect of cardiomyoplasty certainly cannot be attributed to simple wrapping itself.     

Pineal "synaptic" ribbons evolution over a 24 hour period during two different photoluminous seasons, a comparative and statistical analysis.

A comparative statistical analysis of "synaptic ribbons" evolution over a 24 hour period during two different photoluminous seasons (September, and winter) is carried out. Seventy male rats were used. Statistical analysis involved the Kolmogorov-Smirnov test, variance analysis, the Student t-test and Pearson's correlation test. The results show that "synaptic ribbons" evolve during the circadian phase and through two different seasons, with a clear and marked influence of point-time (p < 0.0001) and season (p < 0.0001).     

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.