Response to highly active antiretroviral therapy according to duration of HIV infection

OBJECTIVE: To evaluate whether duration of HIV-1 infection influences the response to highly active antiretroviral therapy (HAART). DESIGN: Prospective study of individuals (Italian Seroconversion Study cohort) with well-estimated dates of HIV-1 seroconversion. METHODS: This analysis included 277 participants who began HAART (defined as three antiretroviral drugs used in combination). Cox regression models were used to evaluate the association between duration of infection (as categorical variable [7.5 years from seroconversion] or continuous variable) and an immunologic (rise in CD4 count >100 cells/mm3) and a virologic (decline in plasma HIV-RNA to unquantifiable levels) outcome. All analyses were stratified by center of recruitment and adjustment, when used, was for gender, age at inception of HAART, injection drug use, previous antiretroviral therapy, lag-time between positive and negative HIV test result, year of starting HAART, clinical stage, CD4 count, and HIV-RNA at time of HAART. RESULTS: HAART was initiated a median of 6.4 years after seroconversion. There was a median follow-up of 1.6 years after starting HAART to the calendar cut-off (November 1999). One-hundred-eighty-one (65.3%) patients experienced a decline in viral load to below quantifiable levels and 184 (66.4%) experienced a rise in CD4 >100 cells/mm3. In the Cox models, by 1-year increase in duration of infection, we estimated a lower crude hazard of achieving a CD4 count increase >100 cells (relative hazard [RH], 0.96; 95% confidence interval [CI], 0.92-1.01; p =.09), and a lower hazard of reaching an unquantifiable level of plasma HIV-RNA (RH, 0.97; 95%CI, 0.93-1.02; p =.20). After adjustment, these values became 0.99 (95%CI, 0.93-1.04; p =.62) and 0.98 (95%CI, 0.93-1.04; p =.48), respectively. When duration of HIV infection was considered as a categorical variable, the results were consistent with those already described. CONCLUSIONS: These results suggest that the duration of HIV infection does not seem to play an important independent role in determining the virologic and immunologic responses to HAART.     

Pathological changes according to the severity of asthma

Background There have been many studies concerning pathological changes in bronchial mucosa from asthmatics; however, few studies has been carried out to evaluate pathological changes according to the severity of asthma. Objective This study was designed to evaluate the cellular components in bronchoalveolar lavage fluid (BALF) and histologicai abnormalities in asthmatics according to the severity ot asthma. Methods Bronchoalveolar lavages, bronchoscopic biopsies and ultrastructural examinations were performed in 13 asthmatics and 11 (BAL) or four (biopsies) non-asthmatic controls. The proportions of epithelial cells and eosinophils in BALF were significantly increased in asthmatics and showed significant correlations with PC_20Meth which reflects bronchial hyperresponsiveness. Light microscopic examination revealed loss of epithelium, inllammatory cell infiltrations and thickening of the basement membrane which also showed significant correlation with PC_20Meth. Hypertrophy of airway smooth muscles and hyperplasia of mucous glands were prominent in asthmatics but there was no difference according to the severity of asthma. Ultra-structural examination revealed that basement membrane thickening on light microscopic examination is due to the increased subepithelial collagen deposition with normal thickeness of basal lamina. Conclusion These data suggest that loss of epithelial cells, infiltration of inflammatory cells, especially eosinophils, and increased deposition of subepithelial collagen play major roles in determining the severity of asthma and non-specific bronchial hyperresponsiveness.     

Electroencephalographic changes induced by prolonged exposure to sound

Summary Marked changes of cerebral electrical activity were observed to be induced by intense noise. In animals, high frequency oscillations appeared, and at certain times regular waves appeared in various cortical areas. In man, a depression of the alpha-rhythm, the appearance of a marked beta-rhythm, spike potentials, and a regular rhythm were observed. It is suggested that these changes are produced by activation of the reticular formation of the brain stem brought about by the action of intense sound stimulation.(Presented by Active Member AMN SSSR P. S. Kupalov) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 54, No. 7, pp. 11–13, July, 1962     

Effects of drug-induced changes in resting blood pressure on classically conditioned heart rate and blood pressure in restrained rats

Subsequent to receiving aversive classical conditioning, which led to a decelerative heart rate (HR) conditioned response (CR) and a pressor-depressor blood pressure (BP) CR, three separate groups of restrained rats received intravenous infusion of sodium nitroprusside (40 micrograms/mg/min) to lower baseline BP, phenylephrine (17 micrograms/mg/min) to raise baseline BP, or an equivalent volume of saline. Conditioning test trials during infusion revealed that hypotension produced by sodium nitroprusside eliminated the HR CR and transformed the BP CR into a pressor-only reaction. Hypertension produced by phenylephrine facilitated the HR CR and changed the BP CR to a pressor-only response on selected trials in which baseline BP increases and baseline HR decreases were within restricted limits. Following drug withdrawal, the HR CRs of both drug groups and the BP CR of the phenylephrine group were attenuated. The unconditioned responses to the shock unconditioned stimulus under phenylephrine were exaggerated and consisted of tachycardias and depressor BP changes, whereas under sodium nitroprusside reduced tachycardias and depressor activity occurred. The results suggested that the loss of the vagally mediated HR CR under sodium nitroprusside was due to baroreceptor-controlled inhibition of vagal discharge and that the enhancement of the HR CR under phenylephrine was due to baroreceptor-influenced facilitation of vagal discharge.     

Umbilical arterial blood gas and perinatal outcome in the second twin according to the planned mode of delivery

Purpose: To compare umbilical arterial gas parameters in the second twin of twin pregnancies according to the mode of deliveryMethods: We retrospectively analyzed the medical records of twin deliveries after 34 weeks of gestation for 3 years. Excluding the cases which underwent emergency cesarean delivery during trial of labor, a total of 79 twin gestations had umbilical arterial blood gas values available and were and divided into cesarean delivery group (N=40) and vaginal delivery group (N=39). The mean differences of umbilical arterial blood parameters and the Apgar score between the first and second twin in each pregnancy were compared according the mode of delivery.Results: The differences of umbilical arterial gas parameters between twin siblings showed no significant difference according to the mode of delivery. With regard to the 1 minute and 5 minute Apgar scores, the differences between twin siblings are significantly increased in vaginal delivery group compared to cesarean delivery group (p=0.048, and p=0.038, respectively). In comparing the 28 cases delivered vaginally with an inter-twin delivery interval < 10 minutes and 40 cases delivered by cesarean section, no significant differences were observed in the umbilical arterial gas parameters and Apgar scores.Conclusion: The inter-twin umbilical arterial blood gas parameters according to the mode of delivery showed no difference. For twin deliveries, it is relatively safe to plan for a vaginal delivery, but an effort should be made to reduce the inter-twin delivery interval time.     

Changes in CD45 isoform expression vary according to the duration of T-cell memory after vaccination.

Healthy young (< 40 years) and elderly (< 60 years) adults were immunized with the 1992-1993 preparation of trivalent influenza vaccine, and changes in CD45 isoform expression on peripheral blood lymphocytes were measured in the pre- and postvaccination periods. Fluorescence-activated cell sorter analysis was used to study T-cell subsets in fresh peripheral blood lymphocytes (day 0) and after 6 days of culture with live influenza virus. We have reported previously that the interleukin-2 response to the stimulating strain of virus, A/Texas/16/89, did not decline until 26 weeks postvaccination. In ex vivo CD4+ subsets, this interleukin-2 response was paralleled by a > 10% increase in the proportion of cells expressing the CD45RO+ phenotype following vaccination (p < 0.0001). In vitro stimulation had no effect on CD4+ subsets prior to vaccination but, after vaccination, was associated with a > 10% increase in CD45RA+RO+ cells (P < 0.0001). In addition, we have identified a change in the population of cells that express a CD45 isoform that is neither CD45RA nor CD45RO (CD45RA-RO-). At 26 weeks postvaccination, the proportion of CD45RA-RO- cells in ex vivo CD4+ peripheral blood mononuclear cells increased by approximately 15% from that measured at the earlier postvaccination time points (P < 0.0001). In vitro stimulation with influenza virus resulted in a further 20% increase in the proportion of CD45RA-RO- cells (P < 0.0001). The CD45RA-RO- phenotype may identify a population of cells undergoing apoptosis (programmed cell death) that limits the duration of helper T-cell (CD4+) memory after vaccination.     

Psychoactive drug-induced changes of interhemispheric EEG amplitude relationships

Analyses of the EEG amplitude levels (integrative method) in the right (R) and left (L) occipital areas of human subjects reveal that there exists in most subjects a R/L difference, and that certain psychoactive drugs can change the relationships which prevail under normal conditions (lateralization). Stimulants tend to decrease interhemispheric differences while, on the contrary, following drug-induced euphoria, these differences are increased. Hallucinogens can reverse lateralization; neuroleptics produce a decrease in the variability of amplitude ratios. Sedatives, minor tranquillizers and placebo are without effect. With hallucinogenic drugs, changes similar to those occurring in man have also been obtained in rabbits.A preliminary communication of these results was presented at the Fifth International Congress of Pharmacology (San Francisco, USA, July 1972).     

Smoking induced changes in EEG two-dimensional maps and blood gas analysis

Summary The effects of smoking on mental function were investigated by the two-dimensional EEG mapping method, and the results were analyzed in conjunction with blood gas data that had been obtained simultaneously. Healthy medical students from the National Defense Medical College were used as the subjects for this experiment. They live in the same dormitory and a similar lifestyle to regular military personnel. Tests were carried out on two successive days, and in between the two testing sessions, each subject was requested to refrain from smoking for 24 hours. During the testing sessions, EEGs were recorded with eyes closed, before and after smoking. Two-dimensional maps were generated by unbiased polynomial interpolation for alpha activity. Various blood chemical measurements were made, among which, partial pressure of carbon dioxide (pCO₂) and percentage of carbon monoxide hemoglobin (%COHb) were studied in relation to EEG changes. The smoking induced wide-spread amplitude decrease in the alpha maps. After 24 hours of withdrawal, alpha amplitude increased, although it decreased again when smoking resumed. Either the correlation between EEG amplitude and %COHb, or the correlation between EEG amplitude and pCO₂, was examined in three regions (anterior: A, middle: M and posterior: P) of the two-dimensional maps in both slow and quick smokers. There were no correlations observed between changes in the EEG amplitude and changes in %COHb induced by smoking, in any of the three regions in either fast or slow smokers. However, there was a clear correlation between changes in the EEG amplitude and changes in pCO₂ in quick smokers, the correlation coefficient being approximately -0.7. It is possible that this relationship was due to hyperventilation, since the same tendency was not observed in slow smokers.This work was supported by a grant from the Smoking Research Center.     

解剖学课堂学生心理变化与教学方法

如何开创新的教学模式，组织安排好每一单元课堂教学活动，是影响教学质量的重要环节。根据多年教学实践认为，在解剖学每一单元教学活动中，学生思维注意力具有较明显的“思维分散”、“思维集中”和“思维疲劳”三个心理变化阶段。每个阶段持续时间和表现，可因学生入学时的层次以及社会经历不同而有较大差别。教师根据这些心理变化特点，有针对性地采用不同的教学模式和方法，为本文予以探讨的课题。