Th2 responses induce humorally mediated injury in experimental anti-glomerular basement membrane glomerulonephritis

Clinical and endocrinological effects of exemestane (6-methylenandrosta-1,4-diene-3,17-dione; PNU 155971) were evaluated in an open Phase I study. Thirteen postmenopausal women suffering from advanced breast cancer received exemestane in escalating doses over a 12-week period. Starting on 5 mg once daily (o.d.), exemestane was subsequently escalated at 2-week intervals to 10, 25, 50, 100, and 200 mg o.d. Each patient subsequently continued treatment on the highest tolerated dose until time of progression. One patient terminated treatment after 6 days due to diarrhea that was probably not related to drug therapy, although a relationship could not be excluded. Apart from this, no serious side effects were seen during the dose escalation period. Exemestane (10 mg o.d.) caused maximal suppression of plasma estradiol (E2) and estrone (E1) to a mean of 14.6 and 5.8% of pretreatment levels, respectively, whereas 25 mg of exemestane o.d. suppressed estrone sulfate (E1S) to 8.9% of pretreatment levels. No fall in adrenal steroid levels was recorded. Exemestane (5 mg o.d.) suppressed urinary E2 and E1 to a mean of 11.9 and 12.2% of pretreatment levels, respectively. Administering exemestane at doses of 50-200 mg o.d. caused no further suppression of urinary E1, whereas urinary E2 fell to 6-7% of pretreatment levels. Median time to progression was 63 weeks. We conclude that exemestane is a well-tolerated aromatase inhibitor that effectively suppresses plasma and urinary estrogens in postmenopausal patients with breast cancer.     

A study on the relapse and its potential causes in pulmonary tuberculosis

A retrospective cohort study was conducted to acquire the general picture of relapse in pulmonary tuberculosis in China and to clarify the relationship between potential causes and relapse rate. All data were collected from 4,797 initial sputum-positive cases. Results showed: (1) Bacteriological relapse rate within two years after chemotherapy was 4.6%. (2) Cumulative relapse rates within half a year and a year only accounted for respectively 28% and 43% of that within two years after chemotherapy. (3) Patients over 60 years old, with drug-resistant bacilli, with long excretion of bacilli, or with residual cavity(ies) or bacterial-negative conversion of less than 3 months at the end of treatment, were the high risk population of relapse.     

A THEORETICAL MODEL FOR PREDICTING FATIGUE CRACK GROWTH RATES IN FIBRE-REINFORCED METAL LAMINATES

This paper is concerned with the development and application of an analytical model for predicting fatigue crack growth in fibre-reinforced metal laminates (FRMLs). An analytical model for the distribution of bridging traction is first introduced. Based upon observations of the delamination shapes in FRMLs under fatigue loading and a model for characterizing delamination growth in FRMLs, a model for predicting crack growth rates in CCT specimens of FRMLs is developed. The model is applied to two GLARE laminates (2/1, 3/2 lay-ups) under various cyclic stress levels and stress ratios. The predicted crack growth rates are compared with experimental data. The predicted crack growth rates agree well with the experimental results.     

STRESS INTENSITY FACTORS FOR SURFACE CRACKS AT A HOLE BY A THREE-DIMENSIONAL WEIGHT FUNCTION METHOD WITH STRESSES FROM THE FINITE ELEMENT METHOD

Stress intensity factors for semielliptical surface cracks emanating from a circular hole are reported in this paper. The three-dimensional weight function method with three-dimensional finite element solutions for the uncracked stress distribution is used for the analysis. Two different loading conditions, i.e. remote tension and wedge loading, are considered for a wide range of geometrical parameters. Both single and double surface cracks are studied and compared with other solutions available in the literature. Typical crack opening displacements are also provided.     

Laparoscopic evaluation of patients with suspected acute appendicitis

BACKGROUND: High error rates are reported in the clinical diagnosis of acute appendicitis. This study was undertaken to discover what additional value laparoscopy has in the diagnosis of suspected acute appendicitis. METHODS: From April 1995 to November 1996, a diagnostic laparoscopy, before open appendicectomy, was performed in 100 consecutive patients with suspected acute appendicitis. Appendicectomy was performed only if the appendix showed signs of inflammation at laparoscopy or if the appendix could not be visualized. RESULTS: Twenty-four patients were spared an appendicectomy, and in half of them a new diagnosis was established during laparoscopy. The rate of misdiagnosis was 41% in female patients of reproductive age and 8% in male patients. There were no cases of missed appendicitis in this trial, and all removed appendices showed signs of inflammation at histology. CONCLUSIONS: It is safe to rely on the diagnosis made at laparoscopy. Its use for establishing diagnosis before appendicectomy in women of reproductive age is recommended.     

Pathogenic adaptation of Escherichia coli by natural variation of the FimH adhesin

Conventional wisdom regarding mechanisms of bacterial pathogenesis holds that pathogens arise by external acquisition of distinct virulence factors, whereas determinants shared by pathogens and commensals are considered to be functionally equivalent and have been ignored as genes that could become adapted specifically for virulence. It is shown here, however, that genetic variation in an originally commensal trait, the FimH lectin of type 1 fimbriae, can change the tropism of Escherichia coli, shifting it toward a urovirulent phenotype. Random point mutations in fimH genes that increase binding of the adhesin to mono-mannose residues, structures abundant in the oligosaccharide moieties of urothelial glycoproteins, confer increased virulence in the mouse urinary tract. These mutant FimH variants, however, are characterized by increased sensitivity to soluble inhibitors bathing the oropharyngeal mucosa, the physiological portal of E. coli. This functional trade-off seems to be detrimental for the intestinal ecology of the urovirulent E. coli. Thus, bacterial virulence can be increased by random functional mutations in a commensal trait that are adaptive for a pathologic environment, even at the cost of reduced physiological fitness in the nonpathologic habitat.     

Relationship between obesity and risk factors of coronary heart disease in nondiabetics

We analysed the data of 395 nondiabetic obese (BMI 25-42.2, impaired glucose tolerance, IGT, 257 and normal glucose tolerance, NGT, 138) and 482 nonobese subjects (BMI 15.9-24.9, IGT 170 and NGT 312). The blood pressure, plasma glucose, insulin, triglyceride and total cholesterol in obese were higher than that in nonobese, while HDL-c level was lower after controlling for age and sex (P < 0.001). This difference remained to be significant even after the adjustment of age, sex, insulin and 2-hours plasma glucose. Therefore, it was suggested that obesity was easy of access to coronary heart disease risk factors independent of hyperglycemia and hyperinsulinemia.     

The TC21 oncoprotein interacts with the Ral guanosine nucleotide dissociation factor

Serum specimens were collected from 6 species of animals living in 9 states of Malaysia including Sabah, North Borneo in 1993. Antibodies against Japanese encephalitis (JE) virus in these sera were detected by means of hemagglutination-inhibition (HI) and neutralization (NT) tests. By HI test, 702 of 2,152 (32.6%) sera showed positive results. Higher positive rates were obtained by the NT test, in which 1,787 of 1,927 (92.7%) sera had antibodies against JE virus. All serum specimens with positive HI were confirmed as positive by the NT. Swine sera showed especially higher rates of antibody positive and higher antibody titers compared with other animals. These results suggest that JE infections are widely distributed among many animals of Malaysia, and pig is the most susceptible amplifier host for JE virus.