Rate of HIV-1 decline following antiretroviral therapy is related to viral load at baseline and drug regimen

OBJECTIVES AND DESIGN: The dynamics uf viral decline following the initiation of antiretroviral treatment were studied in 29 HIV-1-infected patients participating in a two-arm trial comparing immediate (group A: ritonavir, zidovudine and lamivudine) and delayed (group B: ritonavir supplemented by zidovudine and lamivudine on day 21) triple therapy. Parameters underlying viral dynamics were estimated using mathematical models tailored to these treatment protocols. RESULTS: The decline in plasma HIV-1 density between day 0 and 21 was steeper in group A (-2.27+/- 0.46 log10) than group B (-1.87+/-0.56 log10). In a subset of patients amenable to full mathematical analysis, a short-lived productively infected cell compartment (producing approximately 97% of total virions) decayed with a half-life of 1.0-2.5 days, whereas a long-lived infected cell compartment decayed with a half-life of 18.8-32.8 days. Estimates for the time for the elimination of virus from these two cell populations ranged from 474 to 802 days. The rate of loss of productively infected CD4+ T cells was positively correlated with baseline viral load in group A and in the combined dataset. CONCLUSIONS: These results suggest that HIV-infected cell populations may have a faster turnover in patients with higher viral loads due to higher infection rate parameters, higher rates of virus production, or lower virus clearance rates.     

Central DSP-4 treatment decreases norepinephrine levels and courtship behavior in male zebra finches

In zebra finches, gonadal steroids activate male courtship, including singing, and also strongly modulate norepinephrine (NE) levels and turnover in brain areas regulating courtship behavior. In a previous study, systemic administration of DSP-4 caused significant decreases in courtship singing. These behavioral decrements were correlated with the degree of NE depletion in several vocal control nuclei. In the present study, we attempted to further decrease brain NE levels while minimizing systemic effects by infusing DSP-4 directly into the third ventricle. DSP-4 treatment significantly reduced NE levels in three of six vocal control nuclei and both hypothalamic nuclei sampled without significantly altering dopamine or serotonin levels in any areas. DSP-4-treated males took longer to begin singing and performed fewer song bouts and courtship displays. Interestingly, behavioral deficits were limited to courtship song displays, other behavior patterns, including female-directed behaviors like approach and follow, were unaffected by DSP-4 treatment. DSP-4 treatment appeared to affect singing behavior by causing deficits in initial attentiveness to females and initiation of singing rather than by affecting song structure.     

The use of a Hydroxyapol-containing zinc-eugenol paste for the filling of dental canals in treating periodontitis

Comparative assessment of the efficacy of two-staged treatment of patients with chronic apical periodontitis by hydroxyapol-containing paste and zink-eugenol paste demonstrated the desirability of adding hydroxyapol powder in the radical paste for the treatment of apical periodontitis.     

Expected survival compared with survival of peptic ulcer patients

In analyses of patient survival it is often desirable to compare observed survival curves with expected survival curves based on information obtained from the general population. However, current methods of calculating expected survival curves are difficult to interpret and are often poorly documented. We discuss an alternative formulation of the so-called direct method which we recommend for general use. By simulation, we show that the expected survival curve obtained from this method represents the expectation of a Kaplan-Meier curve for a set of random population controls. Thus, the term expected survival does not refer to the expectation of patient survival, but rather to the expected survival curve for a random set of controls. The alternative methods are discussed, and we illustrate the methods in an analysis of long time survival of a population-based sample of peptic ulcer patients.     

Competition between gas exchange and speech production in ventilated subjects

Competition between airflow requirements for speaking and gas exchange occurs in ventilator-dependent tracheotomized subjects who can 'steal' air from alveolar ventilation during the ventilator's inflation phase to produce sound. We wondered whether these subjects adopted strategies to minimize hypoventilation when speaking, particularly when ventilatory drive and respiratory discomfort are increased by hypercapnia. We recorded speech and ventilatory and speaking volumes in five ventilated subjects during reading and extemporaneous speech. All subjects spoke during the ventilator's inflation (and expiratory) phase, losing approximately 15% of their inspired tidal volume. During induced hypercapnia (15 mmHg increase in PetCO2) which caused shortness of breath, all subjects could still speak adequately. Two subjects 'adapted' to hypercapnia by reducing the air used for speaking during inflation. In contrast, one subject reacted, as normal subjects do, by increasing the airflow per syllable (a mal-adaptive strategy in ventilated subjects). These changes were modest despite the strong hypercapnic stimulus.     

The quality of adolescent friendships: long-term effects?

Retinoic acid (RA) has been implicated in cardiac morphogenesis by its teratogenic effects on the heart, although its role in normal cardiogenesis remains unknown. To define the parameters of RA action in cardiac morphogenesis, we analyzed the patterns of ligand synthesis, response, and inactivation in the developing mouse heart. Activation of a lacZ transgene controlled by an RA response element (RARE) was compared to the localization of the retinaldehyde-oxidizing dehydrogenase RALDH2, the earliest RA synthetic enzyme in the mouse embryo, and to the expression of a gene encoding an RA-degrading enzyme (P450RA). We observed that RALDH2 localization and RA response were virtually superimposable throughout heart development. Initially, both RALDH2 and RARE-LacZ activity were restricted to the sinus venosa in unlooped hearts, but were high in the dorsal mesocardium, while P450RA expression was restricted to the endocardium. Later stages were characterized by a sequential, noncontiguous progression of RALDH2 accumulation and RA response, from the sinus venosa to atria, dorsal-medial conotruncus, aortic arches, and the epicardium. This dynamic pattern of RA response was a direct result of localized RALDH2, since hearts of cultured embryos were uniformly competent to respond to an exogenous RA challenge. These observations support a model in which the influence of endogenous RA on heart development depends upon localized presentation of the ligand, with only limited diffusion from the source of its synthesis.     

Determination of antioxidative potential of biological fluids by using semiconductor chemical sensors

A procedure has been developed for determining the concentrations of superoxide anion radical (SOAR) in aprotonic fluids by using semiconductor chemical sensors. SOAR life in pure solutions is 6.3 hours. Supplements of biological fluids (blood, urine, plasma) increase the rate of SOAR death. There is a great difference in the reaction rate of SOAR with biological fluids in apparently healthy and ill individuals. It is suggested that the above procedure opens vistas both for studies of vital activity and for diagnosis of abnormalities.