Do dual nucleoside regimens have a role in an era of plasma viral load-driven antiretroviral therapy?

This study was undertaken to characterize predictors of response to double nucleoside combinations among 245 human immunodeficiency virus-infected persons initiating antiretroviral therapy. The median time for receiving antiretroviral therapy in this group was 6 months, and the plasma virus load was 58,000 copies/mL. The most commonly prescribed regimens were zidovudine/lamivudine (154 subjects, 63%) and stavudine/lamivudine (46 subjects, 19%). A total of 96 (39%) subjects had their virus load decrease to < 500 copies/mL after the initiation of therapy. Of the 245 study subjects, 102 (41.6%) had > or = 5 months of follow-up and two or more consecutive virus load determinations performed after the start of antiretroviral therapy. Multivariate analysis demonstrated that baseline virus load was the only significant factor associated with obtaining two or more plasma virus loads of < 500 copies/mL. Overall, these data demonstrate that dual nucleoside therapy (using currently licensed agents) cannot reliably achieve a high level of suppression of plasma virus load.     

Oral glutamine challenge in cirrhotics pre- and post-liver transplantation: a psychometric and analyzed EEG study

Latent or sub-clinical hepatic encephalopathy is a recognized complication of cirrhosis and is thought to represent one end of the spectrum of neuropsychiatric impairment, which occurrs as a result of portal-systemic shunting. We studied the psychometric, analyzed electroencephalography (EEG), and venous blood ammonia responses to an oral glutamine challenge in 17 patients with cirrhosis and in 4 normal controls. The cirrhotics were attending for liver transplant assessment and had no clinical evidence of hepatic encephalopathy. The oral glutamine challenge was repeated following liver transplantation. Five of sixteen patients (31%) showed impaired performance on at least one of the baseline psychometric tests. There was a correlation between fasting venous ammonia and choice reaction time (r = .7, P < .01). Following glutamine challenge there was a significant increase in blood ammonia from a mean fasting value ranging between 58 micromol/L to 120 micromol/L (P < .01), between significant prolongation of reaction times of 387 ms to 428 ms (P < .01), and an increase in mean EEG amplitude between 68.5 microV to 78.6 microV (P < .001). Four normal controls who were challenged with glutamine and 6 cirrhotic patients who were challenged with water showed no change in any of these parameters. Following orthotopic liver transplantation (OLT) the eight patients studied had normal baseline psychomotor performance with significant improvements in digit symbol, digit span, information processing, number connection tests (P < .05), and reaction time (P < .005). Posttransplantation, there were no significant changes in blood ammonia, analyzed EEG, or choice reaction time in response to oral glutamine challenge (six patients). We conclude that short lived changes in blood ammonia (in cirrhotics) can cause significant impairment of sensitive tests of brain function and that psychometric performance is improved following OLT.     

Broad-band superluminescent light-emitting diodes incorporating quantum dots in compositionally modulated quantum wells

We propose and demonstrate a technique for tailoring the emission bandwidth of /spl sim/1.3 /spl mu/m quantum dot superluminescent light-emitting diodes. A broadening of the emission is achieved by incorporating the InAs quantum dot layers in InGaAs quantum wells of different indium compositions. These structures exhibit a broader and flatter emission compared to a simple dot-in well structure comprised of wells of identical indium composition.     

Significant correlation between thrombospondin 1 and serine proteinase expression in rheumatoid synovium

OBJECTIVES: The natural history of Helicobacter pylori infection in humans is not well established. We aimed to systematically review the literature on the natural acquisition and spontaneous elimination of the infection and its clinical consequences. METHODS: A broad-based MEDLINE and Current Contents search was performed to identify all related publications between 1986 and 1996. Abstracts from recent major conferences that provided adequate data were also included. RESULTS: The prevalence of H. pylori infection increases with age, the rates being significantly lower in developed countries than in developing countries. However, the overall prevalence is decreasing in both developing and developed countries, which probably is responsible for the steep decline of gastric cancer in some industrialized countries. The natural acquisition of H. pylori infection occurs, for the most part, in childhood, and it appears that the incidence is currently slightly higher in developing countries than in industrialized countries. Spontaneous elimination of the infection also occurs, especially in young children and the elderly. The route of transmission continues to be uncertain, with the best evidence favoring both the gastro-oral and fecal-oral routes. Low socioeconomic status is a major risk factor for acquisition of the infection. Genetics probably plays a role in the acquisition or clearance of H. pylori infection in individuals. CONCLUSIONS: Low rates of natural acquisition and elimination of the infection in adults suggest that it is worthwhile to eradicate the organism from adults, but there should be further evaluation of the need for eradication of H. pylori in children.     

Regulation of protein synthesis in ventricular myocytes by vasopressin. The role of sarcoplasmic/endoplasmic reticulum Ca2+ stores

Protein synthesis in H9c2 ventricular myocytes was subject to rapid inhibition by agents that release Ca2+ from the sarcoplasmic/endoplasmic reticulum, including thapsigargin, ionomycin, caffeine, and arginine vasopressin. Inhibitions were attributable to the suppression of translational initiation and were coupled to the mobilization of cell-associated Ca2+ and the phosphorylation of eIF2alpha. Ionomycin and thapsigargin produced relatively stringent degrees of Ca2+ mobilization that produced an endoplasmic reticulum (ER) stress response. Translational recovery was associated with the induction of ER chaperones and resistance to translational inhibition by Ca2+-mobilizing agents. Vasopressin at physiologic concentrations mobilized 60% of cell-associated Ca2+ and decreased protein synthesis by 50% within 20-30 min. The inhibition of protein synthesis was exerted through an interaction at the V1 vascular receptor, was imposed at physiologic extracellular Ca2+ concentrations, and became refractory to hormonal washout within 10 min of treatment. Inhibition was found to attenuate after 30 min, with full recovery occurring in 2 h. Translational recovery did not involve an ER stress response but rather was derived from the partial repletion of intracellular Ca2+ stores. Longer exposures to vasopressin were invariably accompanied by increased rates of protein synthesis. Translational inhibition by vasopressin, but not by Ca2+-mobilizing drugs, was both preventable and reversible by treatment with phorbol ester, which reduced the extent of Ca2+ mobilization occurring in response to the hormone. Larger and more prolonged translational inhibitions occurred after down-regulation of protein kinase C. This report provides the first compelling evidence that hormonally induced mobilization of sarcoplasmic/endoplasmic reticulum Ca2+ stores is regulatory upon mRNA translation.