The L5178Y/tk+/- mouse lymphoma specific gene and chromosomal mutation assay a phase III report of the U.S. Environmental Protection Agency Gene-Tox Program

The L5178Y/tk+/- (-)3.7.2C mouse lymphoma assay (MLA) which detects mutations affecting the heterozygous thymidine kinase (tk) locus is capable of responding to chemicals acting as clastogens as well as point mutagens. Improvements in the assay to enhance detection of this spectrum of genetic events are summarized, and criteria for evaluating the data are defined. Using these criteria, the Phase III Work Group reviewed and evaluated literature containing MLA results published from 1976 through 1993. The data base included 602 chemicals of which 343 were evaluated as positive, 44 negative, 18 equivocal, 54 apparently inappropriate for evaluation in this test system with the published protocols, and 142 that were inadequately tested, and thus a definitive call could not be made. The overall performance of the assay is summarized by chemical class, and the outcome of testing 260 chemicals in the MLA is compared with Gene-Tox and National Toxicology Program evaluations of rodent carcinogenesis bioassay results for the same chemicals. Based on the Work Group's evaluation of published MLA data for chemicals that were considered adequately tested, it is concluded that for most chemicals the L5178Y/tk+/- mouse lymphoma assay is eminently well suited for genotoxicity testing and for predicting the potential for carcinogenicity.     

Effect of insulin versus sulfonylurea therapy on cardiovascular risk factors and fibrinolysis in type II diabetes

1. The synthesis and release of nitric oxide may play a role in the pathogenesis of peripheral vasodilatation and hyperdynamic circulation observed in liver cirrhosis. In this work, we analysed the synthesis of nitric oxide by the lympho-mononuclear cells of peripheral blood from patients with chronic alcoholic and non-alcoholic liver disease and we identified the isoform of nitric oxide synthase involved in the increased nitric oxide synthesis. 2. Patients were classified following clinical and histological criteria in non-alcoholic cirrhotic, alcoholic cirrhotic and non-cirrhotic chronic liver disease. We studied clinical and analytical characteristics, haemodynamic parameters and endotoxin levels in these patients. 3. Cirrhotic patients showed an increase of cardiac output and a decrease of peripheral vascular resistance. These patients had higher levels of plasma endotoxin than those observed in the control group. N omega-Nitro-L-arginine methyl ester (L-NAME)-inhibitable nitrite production from mononuclear lymphocyte cells was higher in patients than in the control group, the highest levels being in non-alcoholic cirrhotic patients, and the lowest levels in patients with non-cirrhotic alcoholic liver disease. 4. Immunocytochemistry studies revealed a positive immunoreactivity for the inducible isoform of nitric oxide synthase in lympho-mononuclear cells that was more evident in non-alcoholic than in alcoholic cirrhotic patients. By Northern blot, inducible nitric oxide synthase mRNA expression was observed only in lymphomononuclear cells from non-alcoholic cirrhotic patients. 5. Our patients show a correlation between nitric oxide synthesis, endotoxin levels and haemodynamic parameters. 6. These findings indicate that lympho-mononuclear cell stimulation may play a role in elevated nitric oxide production in hepatic cirrhosis. Thus, this increased nitric oxide synthesis could be implicated in the pathogenesis of the haemodynamic disturbances frequently found in cirrhotic patients. This increase seems to be induced, at least in part, by activation of an inducible isoform of nitric oxide synthase.     

Ventricular perforation associated with central venous introducer-dilator systems

BACKGROUND: An erythrocyte sedimentation rate (ESR) of at least 40 mm/h is considered an important requisite for the diagnosis of polymyalgia rheumatica (PMR). However, the relative frequency and clinical features of PMR in patients without a significantly increased ESR are unclear. METHODS: We performed a retrospective study of patients diagnosed as having PMR at the rheumatology divisions of 3 teaching hospitals. The diagnosis of PMR was established, regardless of the ESR, in 201 consecutive patients fulfilling the following criteria: (1) age 50 years or older, (2) severe proximal pain for more than 1 month in at least 2 of 3 areas: neck, shoulder, and/or pelvic girdles, and (3) rapid resolution of the syndrome while taking low-dose prednisone. Patients with giant cell arteritis were previously excluded from the study. The frequency and clinical features of patients with PMR and an ESR lower than 40 mm/h were analyzed. A comparative study between these patients and those with high ESRs was performed. RESULTS: An ESR lower than 40 mm/h was found in 41 patients (20.4%). These patients were younger (P = .02), were more frequently men (P = .006), and experienced a lower frequency of fever (P = .003) and weight loss (P = .07). Furthermore, these patients were characterized by an absence of anemia (P = .002) and a lower frequency of abnormal protein electrophoresis results (P < .001). Otherwise, their clinical syndrome, response to therapy, and frequency of relapses were similar to those of patients with classic PMR. In the entire population of 201 patients, the ESR was related to the length of treatment, number of areas involved, presence of fever, weight loss, and laboratory test result abnormalities, but it was unrelated to the duration of the illness prior to diagnosis. CONCLUSIONS: It is not uncommon to find a patient with PMR with an ESR lower than 40 mm/h. This syndrome is more frequent in men and it is clinically less severe than the classic form of PMR. Its recognition will allow these patients to benefit from an effective treatment with low-dose corticosteroids.     

Human neonatal ovary: proposal of a three-dimensional model

A model of human neonatal ovary is presented, derived from morphometric, evaluations carried out on left ovaries removed from five full-term neonates with a 46, XX karyotype, free from malformations of the genital apparatus. According to this model, the gonad can be represented by a triaxial ellipsoid with a central medullary core surrounded by a cortical stratum of constant thickness. The germinal population, consisting of follicles and primitive cortical tissue, occupies the cortex, intermingled with the interstitium or stroma. In the cortex it is then possible to describe an outer layer formed by primitive cortical tissue, and an inner portion occupied by follicles. The primary and secondary follicles fill the portion near the medulla and the primordial ones are contained in the middle and outer zones. Since the variability observed among ovaries is slight, we can propose a mean model of neonatal ovary in which the spatial relationships among the different components, the total number of follicles and their position in the cortex can be calculated.     

Biapenem versus imipenem/cilastatin in the treatment of complicated intra-abdominal infections: report from a Swedish Study Group

The objective of this study is to describe usual medical management and costs associated with recurrent respiratory infections in subjects with chronic obstructive bronchitis in France. A prospective survey was performed in Autumn 1994 on a national sample of private practice pulmonologists (N = 71). Two hundred forty-four patients, presenting at least one infection of the lower respiratory tract, were included. Bronchitis was the most frequent acute exacerbation observed (94%). Pneumonia concerned 9% of the patients. Biological tests, X-rays and pulmonary function tests were prescribed for, respectively, 59, 65 and 45% of the patients. Following the visit, 15 patients were hospitalized (6%). The direct medical cost per acute exacerbation was estimated 3,289 francs (1994 value) of which 60% were hospital-related. An average 10.4 day sick-leave was prescribed to 21% of patients in employment. For those patients, this sick-leave was associated to an extra-cost of 1,264-1,876 francs for Social Security and of 0-2,553 francs out of pocket per episode varying according to their Benefit Regimen.     

Cigarette smoking, serum lipids, folate, and vitamin B12 in lung cancer

The purpose of our study was to evaluate the effects of cigarette smoking and serum lipids, folate, and vitamin B12 on the development of lung cancer in the Turkish population. The study group consisted of patients with histologically proven lung cancer and the control group comprised healthy smokers being followed in our smoking cessation outpatient department. Smoking history was obtained from all subjects and serum total cholesterol, HDL cholesterol, triglycerides, vitamin B12, and folate levels were measured. Pack/years of cigarettes smoked were significantly higher in the subjects with lung cancer than in the control group (p < 0.01). Serum total cholesterol, HDL cholesterol, triglyceride, serum folate, and vitamin B12 levels were within normal limits in both groups (p < 0.05), but serum vitamin B12 levels were statistically significantly higher (p < 0.01) in the cancer group than in the controls. In our study, we did not observe low levels of serum cholesterol, vitamin B12, or folate in the lung cancer patients.