Randomized clinical trial of tacrolimus- vs cyclosporine-based immunosuppression in pediatric heart transplantation: preliminary results at 15-month follow-up.

BACKGROUND: While Tacrolimus (Tac) and Cyclosporine (Cya) immunosuppression are used after cardiac transplantation (tx), few studies have evaluated their use in pediatric patients. METHODS: We randomized 26 heart transplant recipients (pts) in a prospective, open-label trial to Tac (n = 14) or Cya (n = 12) to compare their efficacy and side-effects. Mean age at tx was 4.2 years for Tac and 5.8 years for Cya. Mean follow-up was 26 months (range: 11-39 months) for Tac and 24 months for Cya (range: 33-13 months). RESULTS: Our data suggest that both regimens are efficacious in the pediatric population. Conversion from Cya to Tac was useful for dealing with persistent rejection, although this sample did not suggest lower incidence of acute cellular rejection in the Tac group. CONCLUSIONS: Further studies are required to establish pharmacokinetic parameters to enhance therapeutic monitoring of these patients to minimize side effects and enhance outcomes.     

On the Use of Paramagnetic Beads and Ferrofluids to Assess and Eliminate the Leukocytic Contribution to Oxygen Radical Generation by Human Sperm Suspensions

PROBLEM: To develop a methodology to determine a) the leukocytic contribution to reactive oxygen species generation by human sperm suspensions and b) the therapeutic value of removing these cellular contaminants. METHODS: Leukocytes were removed with paramagnetic beads or colloidal ferrofluids coated with anti-CD45 antibody. The sperm suspensions were monitored for oxidant generation by chemiluminescence, leukocyte contamination by immunocytochemistry, and fertilizing potential using zona-free hamster oocytes. RESULTS: Percoll®-prepared human sperm suspensions exhibited a competence for PMA-induced reactive oxygen species generation which was significantly correlated with leukocyte contamination. However, the purified spermatozoa remaining after paramagnetic bead treatment, also demonstrated an intrinsic capacity for PMA-responsive reactive oxygen species generation and, freed from the oxidative stress created by the leukocytes, exhibited a significantly enhanced capacity for sperm-oocyte fusion. CONCLUSIONS: Although human spermatozoa can generate reactive oxygen species, sperm function is inhibited by the additional oxidative stress created by contaminating leukocytes. Removal of these cells with paramagnetic beads enhances fertilizing potential.     

The characterization and pathological significance of gastric Campylobacter-like organisms in the ferret: a model for chronic gastritis?

Gastric campylobacter-like organisms (CLO) were isolated from gastric tissues removed at sacrifice from 17 mature ferrets; all animals were colonized, but no macroscopic mucosal lesions or histological features of chronic gastritis were seen. The isolates resembled Campylobacter pylori in many cultural and biochemical characteristics, and produced substantial urease activity, but there were sufficient differences from C. pylori to suggest that ferret gastric CLO represents a separate species. Comparison of human C. pylori and ferret gastric CLO may help to elucidate the pathogenicity of the former in patients with gastritis, and the ferret may serve as a useful animal model for the study of C. pylori infection.     

实验性视网膜光化学损伤中的蛋白激酶C

目的：研究实验性视网膜光化学损伤中蛋白激酶C(protein kinase C，PKC)活性的改变；探索地塞米松(dexamethasone，DXM)对视网膜中PKC活性的影响。 方法；48只SD大鼠分为对照组和DXM组，后者于光照前3天开始，连续5天腹膜腔注射DXM 1mg/(kg·d)。经(1 900±106.9)Ix的绿色荧光灯(λ＝510nm～560nm)连续照射24小时后的6小时和1、3、7、14天，进行视网膜PKC活性检测。 结果：光化学损伤后视网膜中的PKC活性在短暂的上升后即出现持续性的下降；DXM对PKC的活性改变无明显作用。 结论：光化学损伤中的视网膜功能障碍可能与PKC活性的持续降低有关。 （中华眼底病杂志，1997，13：78-80）     

Amphetamine affects the extinction of self-stimulation differently in prefrontal cortex and posterior hypothalamus of rats

The effects of amphetamine on the extinction of intracranial self-stimulation (ICSS) and on postextinction ICSS performance were examined in rats implanted with electrodes either in medial prefrontal cortex (mPFC) or in the posterior hypothalamus-ventral tegmental area (PH-VTA). Lever-pressing for ICSS was allowed to stabilize in daily 15-minute sessions before each animal was exposed to 5 minutes of extinction (responding without reward). Animals were administered either 0.25 mg/kg d-amphetamine or saline before baseline, extinction and postextinction sessions. After amphetamine treatment, the number of lever presses during extinction was higher in mPFC animals and lower in PH-VTA animals compared with saline-treated controls. Rates did not change immediately after extinction but, one day later, rates had increased in all saline-treated animals (both PH-VTA and mPFC animals) and had decreased in all amphetamine-treated animals. These findings demonstrated that the effects of amphetamine on the extinction of ICSS were different in cortical and hypothalamic sites, possibly because of regional differences in stimulus-evoked reinforcement and inhibitory processes.     

Moclobemide and specific serotonin re-uptake inhibitor combination treatment of resistant anxiety and depressive disorders

This retrospective study was undertaken with the objective of determining how effective and safe moclobemide, a specific and reversible inhibitor of monoamine oxidase-A (RIMA), is when used in combination with specific serotonin re-uptake inhibitors (SSRIs), in a clinical setting. A thorough chart review was done of all patients with affective and anxiety disorders seen at our centre who received combination treatment with moclobemide and an SSRI. Combination moclobemide-SSRI treatment demonstrated good efficacy in treating treatment-resistant patients. The combination treatment was well tolerated with very few drug interactions. Dosages should be started low, titrated slowly and carefully, and patients should be monitored closely.     

The role of intestinal flora on the interactions between nonparenchymal cells and hepatocytes in coculture

Kupffer cells are exposed directly to a number of factors in the portal circulation that can modify or regulate their responses to septic stimuli. The gut represents a potential source of a number of these factors including endotoxin, lymphokines, and prostaglandins. We examined Kupffer cells from germfree rats and germfree rats exposed to endotoxin or bacteria via their GI tracts to determine the importance of the intestinal flora in maintaining or modulating Kupffer cell responses. Kupffer cells from germfree animals were reduced in numbers and failed to respond to LPS in Kupffer cell: hepatocyte coculture. When germfree rats were exposed to bacterial endotoxin or bacteria via the gastrointestinal tract their Kupffer cells increased in numbers to normal and the cells responded to LPS in culture. Intestinal overgrowth with Escherichia coli for 2 days activated the Kupffer cells and significantly increased Kupffer cell sensitivity to LPS. These data suggest that the environment of the gastrointestinal tract is important for normal Kupffer cell responses and that intestinal bacterial overgrowth can modify Kupffer cell responses to septic stimuli.