A prospective randomized trial of colchicine in prevention of liver cirrhosis in chronic hepatitis B patients

Background : The clinical course of chronic hepatitis B is variable. Patients with hepatic decompensation, bridging necrosis or an alpha-fetoprotein level greater than 100 ng/mL during an exacerbation of hepatitis have a high risk of developing cirrhosis. This study was conducted to evaluate the effect of colchicine in the prevention of cirrhosis in such patients.
Methods : Patients with risk factor(s) were randomized to receive either colchicine 5 mg/week or no specific treatment, the end point being development of cirrhosis.
Results : After a follow up period of 4 years, the treatment group had a marked reduction in exacerbations of acute hepatitis (32% vs. 63%/patient/year, P <0.005). Seven out of 38 patients in the treatment group and 10 out of 27 patients in the control group developed cirrhosis. The calculated cumulative incidence of cirrhosis by the end of first, second, third and fourth years in the treatment group was 8.7, 18.6, 32 and 32%, respectively. The corresponding figures in the control group were 30, 35.5, 46.3 and 73.2%, respectively, with a P -value of 0.057.
Conclusions : The results suggest that colchicine may prevent cirrhosis in chronic hepatitis B patients with risk factor(s), possibly by suppressing exacerbations of hepatitis through an anti-inflammatory effect.     

Therapeutic efficacy of miconazole on deep-seated fungal infections in the respiratory tract system

We evaluated the therapeutic efficacy of miconazole (MCZ, Florid-F inj.), a new antifungal agent for parenteral use, in deep-seated fungal infections of respiratory tract system. A daily dose of 400-1,800 mg of MCZ was given intravenously for 12-38 days (mean: 23.4 days) to 7 patients: 2 patients with pulmonary aspergillosis, 1 patient with bronchial aspergillosis, 1 patient with pulmonary candidiasis and 3 patients with candidemia. One additional patient with pulmonary aspergillosis received three instillations of 20 mg of MCZ into the thoracic cavity. The clinical effects were excellent in 1, good in 4 and poor in 3 patients. The efficacy rate was 100% in 5 cases with respiratory fungal infections but 3 cases with candidemia did not respond well to the treatment. Four strains each of Aspergillus sp. and Candida sp. were identified as causative organisms. Seven of the 8 strains were eradicated by administration of MCZ. Side effects observed were irritation and heat in a leg in 1 patient, hyperlipoidemia in 2 patients and eosinophilia in 1 patient. The adverse reactions disappeared after the completion of the therapy. From the above results, we conclude that MCZ is one of the most useful antifungal agents for parenteral use as a first choice on deep-seated fungal infections in the respiratory tract.     

大脑后动脉交通前段及其内穿支研究

本文介绍Willis动脉环后半环大脑后动脉及其内穿支的显微解剖,大脑后动脉交通前段内穿支是脑深部的重要供血血管之一,100％的病例双侧具有该血管。     

Anti-thyroid drugs decrease mucosal damage in a rat model of experimental colitis

Background : Methimazole, an anti-thyroid drug, was recently found to be useful in the treatment of systemic lupus erythematosus and other autoimmune diseases. Moreover, decreased thyroid hormone production is associated with a variety of immunological manifestations, such as reduced activation of CD4⁺ cells, increased CD8⁺ cell activity and reduced soluble IL-2 receptors. In the present study we examined the effects of methimazole and propylthiouracil on a rat model of experimental colitis.
Methods : Colitis was induced by intracolonic administration of 30 mg trinitrobenzene sulphonic acid (TNB). Two weeks prior to induction of colitis, rats were treated by either methimaziole (0.04%) or propylthiouracil (0.01%) in drinking water after a week of free access to water. Rats were sacrificed 48 h or 7 days after induction of colitis. The colon was isolated, rinsed with ice-cold water and weighed. Damage was assessed both macroscopically and microscopically and myeloperoxidase (MPO) activity determined.
Results : All treated rats were hypothyroid as manifested by a significant elevation of thyroid stimulating hormone (TSH), by comparison with the control groups (mean -1.82±0.40 versus 0.11±0.02 mmol/L, respectively). The inflammatory response elicited by TNB resulted in severe mucosal damage 48 h after damage induction, which persisted for 7 days. Pre-treatment with either methimazole 0.04% or propylthiouracil 0.01% significantly decreased mucosal damage macroscopically (lesion area, lesion score and segmental weight) microscopically and also significantly decreased MPO level at both time points ( P <0.01).
Conclusions : Methimazole and propylthiouracil significantly reduce mucosal damage and colonic weight in a rat model of colitis. The mode by which they do so remains to be studied.     

The in vitro fertilisation programme at Tygerberg Hospital and the University of Stellenbosch. Five years' experience, April 1983-January 1988

The results of the in vitro fertilisation programme at Tygerberg Hospital for the period April 1983 to January 1988 are presented. Of the 1117 laparoscopies performed, 825 patients reached the transfer stage. A live-birth rate of 9.3% was achieved. The pregnancy rate after transfer of 4 embryos was 25.9% compared with 15.4% after 2 embryos and 10.8% after 3 embryos (P = less than 0.0001). The multiple pregnancy rate was 2.8% in the group receiving 2 embryos and 11.7% and 10.4% in those receiving 3 and 4 embryos, respectively. Of the 77 successful pregnancies (90 babies), 1 baby died at 34 weeks' gestation as the result of abruptio placentae due to preeclampsia and 1 cot death occurred. The only congenital abnormality encountered was a cleft palate.     

Head lice in Israeli children: parents' answers to an epidemiological questionnaire

BACKGROUND: The aim was to determine the influence of the socioeconomic status of the family and the hygienic practices in the home on the prevalence of head lice infestation in children. METHODS: The study was carried out by analyzing the answers to a standardized epidemiological questionnaire given to parents of school children aged 4-17 in Bet Shemesh, a medium-sized urban town 25 km from Jerusalem. RESULTS: Of 3,000 questionnaires distributed, 958 (31.9%) were completed and returned. The majority of the children (72.4%) had been previously infested with lice. Half of them had other family members, mainly brothers and sisters, who had been infested in the past with lice. In 97.5% of the families the mother was responsible for examining the children for lice, and for carrying out treatment when infestation was present. An association was found between presence of lice infestation and mother's education, age of child, and frequency of shampooing, combing, and examination for lice. There was no association between infestation rates and mother's country of origin, crowding in the home, and the sharing of combs, brushes, hats, scarves, towels, and clothes. CONCLUSIONS: There is evidence that the incidence of lice infestation depends on the hygienic practices in the home rather than on the socioeconomic status of the family or sharing of personal articles among family members.     

Monoclonal antibody analysis of glomerular, tubulo-interstitial infiltrating immune cells in various glomerulonephritis

To investigate the role of cell-mediated immunity (CMI) in glomerulonephritis (GN), we identified the infiltrating immune cells both within the glomerulus and in the interstitium. Frozen sections from 103 patients with various forms of GN: 10 with minor glomerular abnormality (MGA) as control, 10 with minimal change nephrotic syndrome (MCNS), 10 with membranous nephropathy (MN), 9 with focal glomerulosclerosis (FGS), 30 with IgA nephropathy (IgAN), 22 with acute post streptococcal glomerulonephritis (APSGN), and 2 with rapidly progressive glomerulonephritis (RPGN) were examined using monoclonal antibodies (MoAb) by indirect immunoalkaline-phosphatase labelling. In most glomerulonephritis, monocyte/M phi and helper/inducer T cells were predominantly infiltrating in the interstitium, but intraglomerular infiltration was rare, except for APSGN. This interstitial infiltration increased proportionally to the level of serum creatinine, and was most prominent in RPGN. Apparently different distribution was seen in APSGN, that is, prominent increase in total number of intra-glomerular monocyte/M phi infiltration with slightly increased T cells. The change was correlated with time after onset; namely the more leucocytic infiltration was observed when the tissue was taken earlier. These data suggest that in APSGN, monocyte/M phi accumulate in glomeruli via cell mediated immunity in addition to humoral immune mechanism resulting in glomerular hypercellularity, whereas in most chronic glomerulonephritis interstitial leucocyte infiltration, particularly helper T cells and monocyte/M phi may play an important role in the progression of glomerulonephritis.     

Pharmacological studies of 6-amidino-2-naphthyl 4-[(4,5-dihydro-1H-imidazol-2-yl)amino]benzoate dimethanesulfonate. Effects on experimental pancreatitis

The effects of FUT-187 (6-amidino-2-naphthyl 4-[(4,5-dihydro-1H-imidazol-2-yl)amino]benzoate dimethanesulfonate, CAS 103926-82-5), a novel synthetic protease inhibitor, were examined in experimental rat and canine models of pancreatitis. 1. FUT-187 significantly increased the survival of rats with trypsin- and phospholipase A2-induced pancreatitis in a dose-dependent manner (10-100 mg/kg, p.o.). 2. FUT-187 decreased plasma enzymatic activity reflecting the degree of pancreatitis in rats with ethionine-induced pancreatitis, and showed a tendency to ameliorate histopathological changes in the pancreas (10-100 mg/kg p.o.). 3. FUT-187 (10 mg/kg) produced an obvious improvement of various biochemical parameters of pancreatitis and also reduced histopathological changes in the pancreas in animals with experimental pancreatitis produced by the closed duodenal loop method. In addition, FUT-187 significantly increased the survival of dogs when given by direct administration into the lumen of the closed duodenal loop. The therapeutic effects of FUT-187 in experimental pancreatitis were nearly equal in most instances to those of camostat mesilate. Thus, FUT-187 would appear to be an effective new agent for the treatment of pancreatitis.     

Integration and differentiation of human embryonic stem cells transplanted to the chick embryo.

Human embryonic stem (ES) cells are pluripotent cells that can differentiate into a large array of cell types and, thus, hold promise for advancing our understanding of human embryology and for contributing to transplantation medicine. In this study, differentiation of human ES cells was examined in vivo by in ovo transplantation to organogenesis-stage embryos. Colonies of human ES cells were grafted into or in place of epithelial-stage somites of chick embryos of 1.5 to 2 days of development. The grafted human ES cells survived in the chick host and were identified by vital staining with carboxyfluorescein diacetate or use of a green fluorescent protein-expressing cells. Histologic analysis showed that human ES cells are easily distinguished from host cells by their larger, more intensely staining nuclei. Some grafted cells differentiated en masse into epithelia, whereas others migrated and mingled with host tissues, including the dorsal root ganglion. Colonies grafted directly adjacent to the host neural tube produced primarily structures with the morphology and molecular characteristics of neural rosettes. These structures contain differentiated neurons as shown by beta-3-tubulin and neurofilament expression in axons and cell bodies. Axons derived from the grafted cells penetrate the host nervous system, and host axons enter the structures derived from the graft. Our results show that human ES cells transplanted in ovo survive, divide, differentiate, and integrate with host tissues and that the host embryonic environment may modulate their differentiation. The chick embryo, therefore, may serve as an accessible and unique experimental system for the study of in vivo development of human ES cells.     

Penetration and distribution of three lipophilic probes in vitro in human skin focusing on the hair follicle.

Fluorescent model substances of increasing lipophilicity (Oregon Green) 488, Bodipy, FL C5 and Bodipy 564/570 C5) were selected to enable the visualization in the skin using confocal laser scanning microscopy. After measuring the penetration for 18 h, the nonfixed human scalp skin was imaged from the bottom parallel to the stratum corneum and in a cross-section view perpendicular to the skin surface. The images were evaluated by calculating relative accumulation values for different penetrants. The studies indicate that the penetrated amount is highest for Bodipy FL C5 (medium lipophilicity) and lowest for Bodipy 564/570 C5 (high lipophilicity) whereas Bodipy 564/570 C5 (high lipophilicity) reveals the highest relative accumulation in parts of the hair follicle compared to Oregon Green 488 (low lipophilicity). The addition of 30% (v/v) ethanol to the donor phase of substance with a low lipophilicity increases the follicular delivery. From our results we conclude that delivery to the hair follicle can be improved by increasing the drugs lipophilicity and optimizing the composition of the donor phase. However, no conclusion can be drawn about the actual route of transport to the hair follicle.