MAO-A inhibition in brain after dosing with esuprone, moclobemide and placebo in healthy volunteers: in vivo studies with positron emission tomography

Objective: The aim of the study was to investigate whether or not esuprone binds substantially to MAO-A in the human brain. Methods: In a randomised double-blind placebo-controlled study 16 male healthy volunteers were examined␣with positron emission tomography (PET) with [¹¹C]harmine. Eight of the volunteers were given daily doses of 800 mg esuprone, four were given bi-daily doses of 300 mg moclobemide, and four volunteers were given placebo tablets. PET was performed before initiation of a 7-day treatment period. On day 7, one investigation was made immediately before administration of the drug, representing 23 h after the previous day's treatment for esuprone and 11 h after the last tablets of moclobemide. Further investigations were made 4 h and 8 h after the morning dose on day 7. Results: PET showed a high degree of binding of [¹¹C]harmine, a high-affinity ligand for MAO-A, before the start of treatment, and a marked and similar reduction after treatment with esuprone and moclobemide. A slight tendency for normalisation of enzyme binding was observed at the last time point. In the placebo group no change was observed. Plasma kinetics of esuprone showed a rapid elimination with a half-life of about 4 h. Conclusion: The study demonstrates that esuprone was comparable to moclobemide in its effect on MAO-A inhibition in the brain at the doses given. This is an illustration of the potential of PET to monitor drug effects directly on target biochemical systems in the brain in human volunteers, and the possibility of using these data, rather than pharmacokinetic data, for the determination of dosing intervals. Received: 21 August 1996 / Accepted in revised form: 22 November 1996     

Prospective study of antigenemia,plasma viremia and lymphocytic viremia in HIV-infected hemophiliacs

A total of 186 blood samples from 24 HIV-1 seropositive hemophiliac patients, monitored every four months for 29 months, were investigated for the presence of viral antigen in plasma. In addition, peripheral blood mononuclear cells (PBMC) were cultured for HIV-1, using normal PBMC as a target for replication. Antigenemia was detected in 51 % of the patients and from PBMC in 87.5 % of the patients. The incidence of HIV isolation in asymptomatic patients (42.8 %) was similar to that found in symptomatic patients (51.4 %). Patients with opportunistic infections had a higher incidence of lymphocytic viremia (p<0.05). Plasma viremia was closely associated (p<0.05) with low CD4+ counts and infection progression. The persistence of antigenemia was also a marker of a poor clinical course. In treated patients, plasma viremia was the marker that better correlated with the clinical course, and it did not appear during the first nine months of therapy. Zidovudine doses of >500 mg/day significantly lowered the appearance of antigenemia and lymphocytic viremia (p<0.05).     

浅谈对传染科护士素质的要求与体会

根据笔者在传染科病房工作中的体会,从六个方面针对传染科工作的特殊性和存在的共性分别阐述了传染科护士在工作中如何高标准、严要求自己,如何对病人做到到位的护理,旨在提高传染科病房的整体护理质量,从而把更多的实惠让利于患者。     

Biomonitoring of genotoxic exposure of aluminium plant workers.

Humans are environmentally and occupationally exposed to polycyclic aromatic hydrocarbons (PAH). PAH's are a class of tumorigenic compounds which act through metabolic transformation to chemically reactive forms, epoxides, which covalently bind to DNA forming DNA adducts. To evaluate the genotoxic effects of PAH's, air and urine samples were analyzed for PAH. Blood samples were analyzed for benzo(a)pyrene-diol-epoxide-DNA (BPDE-DNA) adducts. New methods for analyzing DNA adducts in lymphocytes have been used to study the genotoxic effects of human exposure to carcinogens. BPDE-DNA adducts in lymphocytes have been used as internal dosimeters of exposure to PAH's and several studies have been conducted. We measured BPDE-DNA adducts in aluminium plant workers with immuno-assay and physico-chemical methods. PAH-DNA adducts were detectable to a lesser extent in subjects working in an aluminium plant compared to subjects working in a coke oven plant.     

Risk factors for diabetic retinopathy in children and adolescents with type I diabetes mellitus

Based on repeated fluoroangiographic examinations in a group of 28 children with type I diabetes mellitus the authors observed progressing diabetic retinal changes. At the end of the three-year observation period they found progress in 32% of the children. They investigated influence of risk factors such as age, duration of the basic disease, its metabolic compensation, sex and HLA typing on the development of diabetic retinopathy.     

Transient protein S deficiency with deep venous thrombosis during Salmonella typhimurium infection

A patient with deep venous thrombosis and low protein S activity during the course of Salmonella typhimurium infection is presented. Although protein S deficiency has been reported in patients with disseminated intravascular coagulation, it was not present in this patient and his protein S activity was normal after the findings of infection and deep venous thrombosis disappeared.     

Effects of nail rigidity on fracture healing

The present study was undertaken to assess the effects of the rigidity of nails on the healing of fractures as evaluated by mechanical strength and rate of bone mineralisation. Ten rats supplied biomechanical data at the start of the experiment and another 100 rats were randomly assigned to 5 groups. In 20 rats no intervention was performed, and they served as a reference group of normal values. Thus, 80 rats underwent a standardised partial osteotomy in the left femur diaphysis prior to manual fracture, reaming and intramedullary nailing. One group received rigid steel nails (group 1) and another, cannulated steel nails (group 2). Group 3 received semi-rigid titanium nails and group 4, soft polyethylene nails. Ten rats in each group were evaluated at 6 and 12 weeks after fracture, and radiographs and callus diameter measurements were performed. Dual-energy X-ray absorptiometry (DEXA) of the bones was performed, and the degree of mineralisation in the callus segment, distal diaphysis and total femur was calculated by the scanner. Subsequently, the bones were tested mechanically by a three-point bending test in a Mini Bionix (MTS) testing system. Radiographs revealed clearly visible fractures at 6 weeks in the intervention groups. At 12 weeks there were no signs of bridging callus in group 4, while the other groups presented scarcely visible osteotomies. The callus area in group 4 was significantly larger at both 6 and 12 weeks than in groups 1–3. In these groups there was a significant decrease in callus area between 6 and 12 weeks. Both maximum bending load, bending rigidity and fracture energy increased significantly in groups 1–3 between 6 and 12 weeks, while bending load and fracture energy increased in group 4. At 6 weeks no significant differences were detected between groups 1–3 in mechanical strength. Group 4 had a significantly reduced maximum bending load and fracture energy at 6 and 12 weeks as well as bending rigidity at 12 weeks. At 12 weeks group 3 had a significantly increased maximum bending load and fracture energy compared with groups 1 and 2. Bone mineral count (BMC) in the callus region in group 4 was significantly reduced at both 6 and 12 weeks. BMC in the callus showed no significant differences between groups 1–3, either at 6 or at 12 weeks. BMC in the distal diaphysis was significantly reduced in groups 1 and 4 compared with group 2 at 12 weeks. Bone mineral density (BMD) in the callus region revealed no significant differences between groups 1–3 at 6 weeks, while at 12 weeks BMD was higher in group 3 than in group 1. BMD in the callus region and total femur in group 4 was significantly reduced at 6 weeks. This study demonstrates that diaphyseal fractures treated with titanium nails with a bending rigidity similar to the intact femur have a higher maximum bending load and fracture energy at 12 weeks than both rigidly or softly nailed fractures. BMD in the callus region was also highest after titanium nailing at 12 weeks. BMD in the distal diaphysis and total femur indicates that the degree of stiffness of the nails have little influence on total bone mineralisation at 12 weeks.