Pilot study to enhance HIV care using needle exchange-based health services for out-of-treatment injecting drug users

The introduction of highly active antiretroviral therapy (HAART) has resulted in marked reductions in mortality and acquired immunodeficiency syndrome (AIDS) incidence across all risk groups; however, the proportionate decrease among injecting drug users (IDUs) has been less impressive. Much of the disparity in benefit to IDUs has been a consequence of decreased access to and receipt of potent antiretroviral combinations. Strategies to increase access to and utilization of HAART have included entry into drug treatment and abstinence. Unfortunately, as few as 15%–20% of active drug users in the United States, and in many other countries, are in drug treatment at any one time. We report a pilot project among out-of-drug treatment IDUs infected with human immunodeficiency virus (HIV); HIV therapy was successfully provided to active heroin injectors using the Community Health Care Van (CHCV) at sites of needle exchange. Subjects were willing to initiate, but were not receiving, recommended HIV therapy and were not interested in formal drug treatment. Antiretroviral therapy regimens were selected and linked to heroin injection timing. Weekly visits were scheduled by CHCV staff to assess adverse side effects and encourage adherence. Of the 13 participants, the mean baseline HIV-1 RNA level and CD4 lymphocyte count were 162,369 (log 5.21) copies per milliliter and 265 cells per milliliter, respectively. By 6 months, the proportion whose HIV-1 RNA was below the limits of detection (<400 copies/mL) was 85% (N=11); 77% (N=10) had nondetectable levels by 9 months. By 12 months, 54% (N=7) had a persistently nondetectable viral load, and the net increase in CD4 lymphocyte count was 150 cells per milliliter. As an additional and unintended benefit of this pilot project, 9 (69%) subjects chose to enter drug treatment after achieving a nondetectable viral load. Entry into drug treatment was associated with durability of viral suppression. This small pilot study suggests that health services based on needle exchange may enhance access to HAART among out-of-treatment HIV-infected IDUs. In addition, it demonstrates that this population can benefit from this therapy with the support of a nontraditional, community-based health intervention.     

大肠杆菌表达耐热DNA聚合酶的纯化和鉴定

目的探讨工程菌表达的耐热ＤＮＡ聚合酶的纯化方法。②方法收集ＩＰＴＧ诱导带有耐热ＤＮＡ聚合酶（ＴＤ聚合酶）基因表达质粒的工程菌株ＤＨ－ＴＤ４，用溶菌酶裂解，６０℃处理后，上清液用硫酸铵沉淀，根据溶解度差异进行粗分级，然后进行离子交换层析细分级，并经聚合酶链式反应（ＰＣＲ扩增）鉴定其活性。③结果纯化的ＴＤ聚合酶具有良好的聚合活性。④结论溶解度差异与离子交换层析是工程菌表达的耐热ＤＮＡ聚合酶纯化的主要步骤。基因工程制备的ＤＮＡ聚合酶可用于ＰＣＲ检测     

Effects of isoflurane on oxygenation during one-lung ventilation in pulmonary emphysema patients

Background: Hypoxic pulmonary vasoconstriction has an important role in human one-lung ventilation (OLV) in the lateral decubitus position under general anesthesia. During OLV, inhalational anesthesia may inhibit hypoxic pulmonary vasoconstriction and the decrease in arterial oxygenation. We studied the effect of isoflurane administration on arterial oxygen tension in chronic obstructive pulmonary disease patients.
Methods: Ten patients who had thoracoscopic laser ablation of bullous emphysema were studied. Patients received 2% isoflurane in oxygen from induction until the first 20 min of OLV in the lateral decubitus position, then were switched to 1% isoflurane lasting 20 min and next were switched to 0.5% isoflurane lasting 20 min. After each 20-min inhalation, pulmonary and hemodynamic parameters were measured. The given concentrations for isoflurane were merely vapor meter concentrations.
Results: PaO₂/FIO₂, Qs/Qt respiratory rate peak inspiratory pressure and PaCO₂ showed no significant changes at each point of isoflurane. Expiratory tidal volume significantly decreased (P<0.05) with 0.5% isoflurane compared to that with 2% isoflurane. Cardiac output, mean arterial pressure, mean pulmonary arterial pressure, systemic vascular resistance and pulmonary vascular resistance showed no significant changes at each point of isoflurane.
Conclusions: In patients with pulmonary emphysema, arterial oxygenation is not affected by low isoflurane concentration during OLV in the lateral decubitus position.     

Guillain-barré syndrome: A series observed at riyadh armed forces hospital january 1984–January 1994

A consecutive series of 47 hospitalized cases of Guillain-Barré syndrome seen over a 10-year period was analysed with respect to: (1) age and sex; (2) antecedent events and seasonal distribution; (3) patterns of clinical presentation; (4) CSF and neurophysiological findings; (5) results of treatment with plasma exchange; and (6) outcome. Twenty-two were children, 20 middle-aged and 5 aged; 37 were male and 10 were female. The most frequent antecedent event was upper respiratory tract infections; a seasonal peak incidence was found in winter. Clinical, CSF and neurophysiological findings concurred with those in the Western literature; 79% of the cases were severe. Plasma exchange performed within the first 2 weeks of onset benefitted in the short-term outcome, i.e. improvement by 1 grade at 4 weeks, but the long-term benefit, i.e. the ability to regain independent locomotion, was questionable. Plasma exchange helped in curtailing the time to walking unaided but had no benefit on the duration of artificial ventilation. Factors associated with an adverse outcome were: age over 15 years, severity of motor electrodiagnostic findings (especially a decreased distal CMAP amplitude and EMG signs of acute denervation), requirement for ventilation and slow progression (>3 weeks) to maximum deficit. After a mean follow-up of 11 months, 55% of the patients regained independent locomotion, which is a comparatively low proportion.     

Effects of commercial chlorophenolate, 2,3,7,8-TCDD,and pure phenoxyacetic acids on hepatic peroxisome proliferation,xenobiotic metabolism and sister chromatid exchange in the rat

The induction of hepatic peroxisome proliferation and drug metabolizing enzymes and of sister chromatid exchange (SCE) in lymphocytes was studied in male Han/Wistar rats after exposing them for 2 weeks to a commercial chlorophenolate formulation (Ky-5) (100mg/kg/ day), to 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD; 0.05–5 g/kg/wk) and to the pure phenoxyacetic acids, 2,4-dichlorophenoxyacetic acid (2,4-D; 100 mg/kg/day) and 2-chloro-4-methylphenoxyacetic acid (MCPA; 100 mg/kg/day). The chlorophenolate formulation and pure 2,4-D and MCPA caused significant increases in the number of peroxisomes in liver cells, although the average size of peroxisomes was not affected, whereas the effect of even the highest dose of 2,3,7,8-TCDD remained small. This finding indicates that dioxin impurities do not account for the peroxisome proliferation induced by chlorophenolate. The relative weight of the liver increased significantly in rats treated with the chlorophenolate formulation and with 2,3,7,8-TCDD (5.0 and 0.5 g/kg). The pattern of induction of xenobiotic metabolizing enzymes showed some differences between chlorophenolate treatment and 2,3,7,8-TCDD treatment. Furthermore, the effects of pure phenoxyacetic acids were different from that seen with chlorophenolate and 2,3,7,8-TCDD. The highest dose of 2,3,7,8-TCDD increased the frequency of SCE in circulating lymphocytes slightly, but significantly.     

The dependence of twitch relaxation on sodium ions and on internal Ca2+ stores in voltage clamped frog atrial fibres

Frog heart relaxation was analyzed under voltage clamp conditions as the tension decay observed after the membrane potential had been returned to its resting value. The tension decayed exponentially with a time constant of 188±3.8 ms SEM. The relaxation rate decreased with the external Na concentration. It fell to about one tenth in a Na-free solution. Increasing the intracellular Na-content by an application of veratrine also decreased the relaxation rate. Thus relaxation seems dependent on the Na gradient. The relaxation rate decreased within one second upon switching from a high to a low Na-containing solution. The relaxation rate reached a minimum before rising slightly to a new steady state value. This rebound may reflect the partial recovery of the Na gradient since a fast variation in [Na]_i follows alteration of [Na]_o. Mn and La ions also slowed relaxation. In a Na-free solution, adrenaline accelerated tension decay, an effect not noticeable in frog heart contained in Ringer solution. Other cAMP-promoting agents, such as dibutyryl-cAMP and aminophylline, also increased relaxation rate.It is concluded that in frog myocardium, part of the decrease of the intracellular Ca²⁺-concentration which occurs during each cardiac cycle could be dependent on a Na–Ca exchange mechanism. The relative importance of this mechanism, versus internal Ca sequestration, in the relaxation of tension may well be greater in contractile tissues whose cells have a large surface/volume ratio.     

Repeated measurement of the gas exchange threshold: relative size of measurement and biological variabilities

If an individual's gas exchange threshold (GET) is measured on several separate occasions, without a change in aerobic fitness, a random variability will be observed. However, it is not known how much of this variability is biologically determined and how much results from variability in the calibration and measurement processes. The statistical re-sampling technique of Bootstrapping was used to estimate the variability of the GET on a single occasion. This analysis provides the first estimate of the combined contribution of breath-by-breath measurement and calibration processes (6%), to the total between-occasion random variability, leaving biological variability to account for the remainder of the imprecision in the measurement of the GET.     

Guanine nucleotide exchange factors of the cytohesin family and their roles in signal transduction

Summary:  Members of the cytohesin protein family, a group of guanine nucleotide exchange factors for adenosine diphosphate ribosylation factor (ARF) guanosine triphosphatases, have recently emerged as important regulators of signal transduction in vertebrate and invertebrate biology. These proteins share a modular domain structure, comprising carboxy-terminal membrane recruitment elements, a Sec7 homology effector domain, and an amino-terminal coiled-coil domain that serve as a platform for their integration into larger signaling complexes. Although these proteins have a highly similar overall build, their individual biological functions appear to be at least partly specific. Cytohesin-1 had been identified as a regulator of β2 integrin inside-out regulation in immune cells and was subsequently shown to be involved in mitogen-associated protein kinase signaling in tumor cell proliferation as well as in T-helper cell activation and differentiation. Cytohesin-3, which had been discovered to be strongly associated with T-cell anergy, was very recently described as an essential component of insulin signal transduction in Drosophila and in human and murine liver cells. Future work will aim to dissect the mechanistic details of the modes of action of the cytohesins as well as to define the precise roles of these versatile proteins in vertebrates at the genetic level.     

Abnormal low density lipoproteins in children with familial hypercholesterolemia — Effet of polyanion exchange resins

Summary In 20 children and adolescents with familial Type IIa hyperlipoproteinemia, serum lipids and lipoproteins were examined before and during treatment with polyanion exchange resins. The composition of LDL was compared to that of healthy siblings. The patients were given Colestyramine (0.6 g/kg body weight) and Colestipol (0.5 g/kg body weight) in a cross-over study for 8 weeks each, after they had been under dietary treatment for at least 12 months. In 6 children, drug treatment had to be stopped due to side-effects. The most common complaints were gastrointestinal discomfort and constipation.Cholesterol, triglycerides and phopholipids were measured in whole serum and cholesterol, triglycerides and Apolipoprotein-B in isolated lipoprotein fractions after ultracentrifugation. Apo-B was determined by radial immunodiffusion.The Apo-B: cholesterol ratio in whole serum and in the LDL fraction was identical in the patients and in the controls. The LDL triglyceride: Apo-B ratio, however, was about 50% lower in the patients. This abnormal LDL composition was not altered by therapy with polyanion exchange resins. HDL cholesterol levels were significantly lower in the patients than in healthy children, and remained low during therapy.The decrease of total and LDL cholesterol (25%) and Apo-B (20%) was similar under both Colestipol and Colestyramine. Triglycerides and phospholipids showed no significant changes in therapy.These studies were supported by grants of the Schweizerische Nationalfonds and the Deutsche Forschungsgemeinschaft (Sonderforschungsbereich 90, Cardiovasculäres System)