Potential for hepatitis C transmission among non-needle/syringe sharing Sheffield drug injectors through the sharing of drug preparation paraphernalia

This study aimed to investigate possible means by which hepatitis C virus (HCV) might be transmitted between drug injecting individuals without the sharing of needles and syringes. A questionnaire-based survey of 143 (out of 287) attendees was conducted at an Infectious Diseases Unit-based HCV clinic. Those patients (all of whom were positive for antibodies to HCV) who asked about risk activities and those that admitted to a history of recreational drug injecting were questioned in detail about their past and current drug preparation practices. Ten per cent denied any history of needle and/or syringe sharing and had no other apparent source of their HCV infection, but instead admitted to having shared drug preparation eqiupment. The existence among drug injectors of such practices with the potential to transmit blood borne viruses is important as it may explain how HCV, which is capable of being spread via very small quantities of blood, can be passed between drug injecting individuals who might otherwise never come into contact with another drug injector's blood. Clinical and public health messages regarding the prevention of the spread of HCV may need to be revised and strengthened.     

An unusual case of adult varicella-associated arthritis

SIR, Arthritis is a rare complication of varicella-zoster virus(VZV) infection in children [1, 2, 3], and most commonly presentsas a monoarthritis. Occasionally, infectious VZV has been isolatedfrom synovial fluid [3] and recently viral DNA has been demonstratedin synovial fluid of individuals with suspected varicella arthritisusing a polymerase chain reaction-based assay [4]. Arthritisassociated with VZV is not well documented in adults, and VZVisolation from the synovial fluid has been reported in onlyone case of an adult with zoster-associated arthritis [5]. We report the case of a 30-yr-old nurse who attended clinicwith a painful,     

Interaction between tumor necrosis factor microsatellite polymorphisms and the HLA-DRB1 shared epitope in rheumatoid arthritis: influence on disease outcome

OBJECTIVE: To investigate whether interactions between tumor necrosis factor (TNF) microsatellite polymorphisms and the HLA-DRB1 shared epitope (SE) are associated with disease severity in rheumatoid arthritis (RA), and to determine if such associations are the same in male and female patients. METHODS: Genotyping for the TNFa microsatellite and HLA-DRB1 was carried out on 157 RA patients with established disease (duration >5 years). Disease severity measures included radiographic damage (the Larsen method), functional assessment by the Health Assessment Questionnaire, history of joint surgery, and global appraisal of outcome by means of a visual analog scale score. The association of severity measures with TNFa microsatellite polymorphisms stratified by SE status, and the interaction between TNFa and the SE, were investigated using stratified analyses and multiple or logistic regression analyses. RESULTS: No significant associations were observed between any single TNFa microsatellite polymorphism and disease severity, although preliminary evidence for an interaction between TNFa6 and TNFa11 was obtained. In the presence of the SE, a significantly worse outcome was associated with individuals carrying TNFa6, and a significant interaction (P = 0.04-0.006) was found between these alleles for all the outcome measures examined except history of joint surgery. In the absence of the SE, the TNFa6 allele was associated with significantly better outcome scores. When examined by sex, significant associations between the TNFa6/SE haplotype and disease outcome measures were found only in females. No statistically significant interactions were found in males, although the TNFa6/SE haplotype was still associated with the worst outcome scores. CONCLUSION: The association of the SE with disease severity in RA is influenced by an interaction with the TNFa6 microsatellite polymorphism. This interaction appears to be acting predominantly in female patients, although the trend is similar in the smaller percentage of males carrying the TNFa6/SE haplotype.     

The vasodilator action of nebivolol in forearm vasculature of subjects with essential hypertension

AIMS: Brachial artery administration of nebivolol increases forearm blood flow in normotensive subjects through activation of the L-arginine/NO pathway. The aim of the present study was to investigate the effect of brachial artery administration of nebivolol in subjects with essential hypertension. METHODS: We studied eight patients with uncomplicated essential hypertension and serum cholesterol less than 6.9 mmol l-1. Antihypertensive medication was discontinued 2 weeks before the study in previously treated patients. Following cannulation of the left brachial artery, saline was infused to establish baseline blood flow, followed by increasing doses of nebivolol (88.5, 177 and 354 microg min-1, each dose for 6 min), followed by saline for 12 min, followed by a 30 min infusion of L-NMMA (2 mg min-1 ). During the final 18 min of the L-NMMA infusion, nebivolol was coinfused using the same doses as before. Forearm blood flow was measured in both arms using venous occlusion plethysmography. RESULTS: Blood flow in the noninfused arm did not change significantly throughout the study. In the infused arm blood flow increased significantly in a dose-related manner during the first series of nebivolol infusions from 2.76+/-0.39 ml min-1-1 100 ml forearm-1 during the baseline period to 4.40+/-0.60 ml min-1-1 100 ml forearm-1 (mean+/-s.e. mean, n=8, P=0.0003 by anova ). L-NMMA antagonized the vasodilator effect of nebivolol: baseline blood flow in the infused arm was 2.41+/-0.53 ml min-1 100 ml forearm-1 and 2.94+/-0.42 ml min-1 100 ml forearm-1 during coinfusion of the top dose of nebivolol with L-NMMA (P=0.0006 for an effect of L-NMMA on nebivolol response). There were no serious adverse events. CONCLUSIONS: Nebivolol causes vasodilation in the forearm vascular bed in subjects with essential hypertension. Since this response is antagonized by L-NMMA, the vasodilatation is probably caused by activation of the L-arg/NO pathway.     

The effect of taste adaptation on salivary flow rate and salivary sugar clearance

To provide an objective measure of the rate of taste adaptation, we measured changes in the flow rate of parotid saliva from 12 subjects while a tastant was infused continuously into their mouths. The tastants employed were sucrose, sodium chloride, and citric acid, each at two different concentrations. With all stimuli, the higher concentration elicited significantly higher initial flow rates, which declined exponentially with time. The half-time for adaptation of flow rate was independent of the nature or concentration of the stimulus and averaged 11.3 sec, which suggests that adaptation follows a single exponential curve. The model of salivary sugar clearance developed by Dawes (1983) predicted that the rate of clearance would be independent of the initial sucrose concentration. However, this model did not take into account the effect of taste adaptation on salivary flow. This process was thus incorporated into the model, which then predicted that the time for clearance would be dependent on the initial sucrose concentration, as found experimentally by Goulet and Brudevold (1984). Hence the process of taste adaptation progressively reduces the stimulated salivary flow rate, which retards the rate of salivary clearance of sugar from the oral cavity.     

新缩瞳剂包公藤甲素人工合成研究

包公藤甲素是从包公藤(Erycibe obtusifolia Benth.)茎中提得的一个新莨菪烷生物碱,具有强烈的缩瞳作用,临床用于治疗青光眼。本文报道用合成的6β-乙酰氧基托品酮为原料,经卤代、水解、还原和N-去甲基化等反应合成包甲素(8)。经光谱测定证实8与天然包甲素的结构完全一致。合成品系外消旋体,其作用机理与天然品相同,而强度则减半。     

Leucocyte mobilization and release of neutrophil elastase following acute insulin-induced hypoglycaemia in normal humans

Insulin-induced hypoglycaemia in humans is associated with the rapid mobilization of leucocytes in peripheral blood. The aim of the present study was to determine whether neutrophil activation, manifested in plasma by neutrophil elastase concentration, occurs in response to insulin-induced hypoglycaemia. Acute hypoglycaemia (mean blood glucose 1.3 +/- 0.2 mmol l-1; mean +/- SD) was induced with intravenous insulin in 15 normal human subjects, and provoked an increase in the neutrophil count from 3.4 (range 1.9-6.5) to 10.7 (9.4-16.3) X 10(9) l-1 (p less than 0.001), and in the total leucocyte counts from 5.7 (4.1-8.1) to 12.8 (11.3-18.6) X 10(9) l-1 (p less than 0.001), with associated elevations in plasma neutrophil elastase concentration from 21 (12-34) to 29 (14-70) micrograms l-1 (p less than 0.05), and in total neutrophil elastase concentration from 5.90 (3.13-8.20) to 25.20 (23.00-52.00) mg l-1 (p less than 0.001). As neutrophil elastase is implicated in the development of vascular disease, this rise in response to hypoglycaemia may be of pathological importance in insulin-treated diabetic patients.