HIV-1 RNA levels and development of clinical disease in two different adolescent populations

HIV infection rates in American youth continue to increase unabated. As adolescent-specific therapeutic interventions are planned, information on HIV infection's course and its predictors becomes critically important for valid and precise study design. We report on age-specific disease rates stratified by estimated time since infected and predictors of HIV disease progression through four clinical categories in two distinct adolescent populations. Adolescents with hemophilia infected through contaminated blood products showed disease progression rates of 18 to 23 events per 100 person-years (PYs) by age and years infected. Predictors of first progression included HIV-1 RNA >30,000 copies/ml (rate ratio [RR], 2.4; 95% confidence interval [CI], 1.5-3.9), antiretroviral monotherapy (RR, 2.4; 95% CI, 1.7-3.3); Latino/a ethnicity (RR, 2.2; 95% CI, 1.2-4.2) and initial intermediate clinical status (RR, 1.9; 95% CI, 1.3-2.9). Sexually-infected adolescents >18 years who had been infected >3 to 6 years had a disease progression rate of 16 events per 100 PY. For these youths, the sole predictor of first progression was viral load (VL) (RR for VL >30,000 copies per ml, 8.4; 95% CI, 2.8-25.1). This article examines the predictive capacity of viral load and evaluates other cofactors for disease progression in different adolescent populations. These data will be of value in clinical trial design.     

The significance of an increased RQ after sucrose ingestion during prolonged aerobic exercise

Summary Four well-trained male subjects worked for periods of 6 h on bicycle ergometers at work loads requiring about 47% of their maximal aerobic capacity. In one series of studies they received only water; in a second series they received 100 g of sucrose containing 100 c U-C¹⁴-labelled sucrose at the beginning of the fourth hour of work. In a third series of experiments, the same subjects received 100 g of non-labelled sucrose at the beginning of the fourth hour. During the experiment without U-C¹⁴-labelled sucrose, blood samples were withdrawn and analysed for glucose, lactate and pyruvate content. Data from C¹⁴O₂ recovery in expired air showed a good correlation with the amount of carbohydrate oxidized during the sucrose experiment. Peak values for the respiratory exchange ratio showed the same time response as those observed for the C¹⁴O₂ in the expired air. It is concluded that the observed rise in RQ after sucrose ingestion, under the conditions studied, is of metabolic origin, resulting from a complete conversion of pyruvate to CO₂.     

Bacteriostatic effects of horse sera and serum fractions on Clostridium welchii type A, and the abolition of bacteriostasis by iron salts

Under a variety of conditions of concentration, Eh, and pH, horse anti-Clostridium welchii serum and normal horse serum exerted similar bacteriostatic effects against Cl. welchii Type A. Ferric iron abolished the bacteriostatic effect when added during the first 2 hours of incubation at Eh+60 mV. Ferrous iron abolished the bacteriostatic effect when added after 3 hours. Ferric iron abolished the bacteriostatic effect at—140 mV. A mixture consisting of horse β₂- and γ-globulins together with human transferrin exerted a bacteriostatic effect similar to that of whole serum. This system responded in the same way as whole serum to the addition of iron. A mixture of horse β₂- and γ-globulins exerted an immediate bactericidal effect which could not be prevented by ferric iron.     

Production and characterisation of monoclonal antibodies specific for staphylococcal enterotoxin B

We have generated monoclonal antibodies (MABs) to staphylococcal enterotoxin B (SEB) in BALB/c mice. Five out of 20 clones which produce anti-SEB MABs have been characterised. Among them, three produce IgG1/kappa, one produces IgM/lambda, and one apparently produces both IgG1/lambda and IgM/lambda MABs. The anti-SEB titres of ascites fluids range from 3200 to greater than 819200 by ELISA. All of the MABs analysed thus far neutralise the mitogenic response of BALB/c splenocytes to a suboptimal dose of SEB. Also, the induction of suppressor cells by SEB in vitro is reversed by pre-incubating SEB with these MABs. Limited digestion with chymotrypsin, trypsin or Staphylococcus aureus V8 protease yields peptide fragments which have been tested by Western-blot analysis. MABs 1FD7 and 2GD9 are specific for the carboxy-terminal end of SEB, and have a similar, but not identical, binding epitope. MABs 2DA3 and 2HA10 bind to intact SEB but not to cleaved products, and are probably specific for antigenic determinants altered by the cleavage or by the denaturing conditions of the electrophoresis, or by both.     

Bradyphrenia in parkinsonism: a historical review

The development over the last 60 years of the concept of bradyphrenia, a syndrome including slowing of cognitive processing in parkinsonism, is described. Psychic akinesia and subcortical dementia are seen as more recent synonyms for this syndrome. Its relations to akinesia and the psychomotor retardation of depression are considered in a historical context, as are its implications for the relation of neurological and psychiatric disorder.     

Influence of different hormonal regimens on endometrial microvascular density and VEGF expression in women suffering from breakthrough bleeding

BACKGROUND: The aim of this study was to quantify blood vessel density (BVD) and immunoreactive vascular endothelial growth factor (VEGF) levels in endometrial biopsies taken from women suffering breakthrough bleeding (BTB) under different exogenous hormonal regimes. METHODS: Endometrial biopsies from women in Melbourne with BTB were divided into four groups: combined-continuous hormone therapy (HT) (estrogen and progestin taken daily), cyclical HT (daily estrogen with progestin for 14 days each cycle), progestin-only, or no HT. Subjects from Barcelona were using the Mirena intrauterine levonorgestrel-releasing system for contraceptive purposes, with menstrual diaries for classification into four groups (amenorrhea, infrequent, regular and prolonged). Control biopsies from Melbourne were included in the study. Endometrial samples were immunostained for VEGF and blood vessel localization using an antibody to CD34. RESULTS: Results showed that BVD was significantly reduced in the progestin-only treated group compared with the other three treatment groups (P = 0.028). In addition, all four Mirena BTB groups had significantly reduced BVD compared with controls. Considerable heterogeneity was observed in VEGF immunostaining within and between individual samples with no major differences between HT or Mirena. CONCLUSION: These results provide strong evidence that unopposed progestins reduce endometrial BVD and that there is no link between VEGF immunostaining and BVD or BTB.     

Expression of immune system-associated antigens by cells of the human central nervous system: relationship to the pathology of Alzheimer's disease

HLA-DR is a class II major histocompatibility complex antigen which in the periphery confers antigen presenting capability. We have previously shown that this marker is profusely expressed in cortex of elderly and Alzheimer's disease (AD) patients, as is the receptor for the lymphokine interleukin-2. We now report presence of additional immune-related antigens in AD, and distributional differences from normal elderly controls. In gray matter, HLA-DR immunoreactivity is normally sparse, except in AD where it co-localizes with virtually all neuritic plaques. HLA-DR positive T cells can be demonstrated in Alzheimer's disease brain tissue, as can instances of apposition between putative brain microglia and T cells. In addition, cells with the morphologic characteristics of astrocytes label for natural killer cell antigen (Leu-11), and apparent lymphocytes bearing T helper and T cytotoxic/suppressor cell antigens are observed. These and other data suggest that the glial proliferation and scavenger activity characteristic of Alzheimer's disease may occur in an immune context and may play an important role in the pathogenesis of the disorder.