Originality benefit and difficulty of clinical research in the West Japan Lung Cancer Group.

The West Japan Lung Cancer Study Group (recently renamed the West Japan Thoracic Oncology Group) is a non-government, non-profit regional scientific organization whose objectives are to conduct clinical research and treatment of lung cancer, and to promote lung cancer expertise among thoracic physicians and radiologists in west Japan. Since 1990, a total of 46 institutes have joined and established the rules of a society. Our major interests are phase II and III trials of chemotherapy in lung cancer. We also have participated in activities with the Japan Clinical Oncology Group (JCOG), which is supported by the National Cancer Center in Tokyo. Additionally, we have conducted phase II and III trials with the support of Japanese pharmaceutical companies. This support allows us to conduct reliable, large-scale randomized trials. Our organization's main problems are unrefined data management and few qualified statisticians, due in part to a lack of funding.

A computer program for pharmacokinetics based on maximum likelihood estimation using the gamma distribution with a probability density function: comparison with the normal distribution.

A computer program is described for maximum likelihood estimation within the gamma or normal distribution which can be used to estimate pharmacokinetic parameters. Pharmacokinetic analysis using this proposed program was investigated by the Monte Carlo method. The assumed pharmacokinetic models were a one-compartment intravenous model and an oral model. The simulated drug concentrations were generated using a 10% S.D. based on the gamma or normal distribution. The gamma or normal distribution was adopted as the probability density function (p.d.f.) to estimate model parameters. The Powell method was used to maximize the logarithmic likelihood. There were no differences in the estimated parameters in terms of statistical and frequency distributions between the gamma and normal distributions using the generated data and the p.d.f. distributions. However, the number of failures to calculate the parameters using the p.d.f. with the normal distribution was more than five times that using the gamma distribution. This result suggests that it may be necessary to evaluate the validity of results computed using the maximum likelihood estimation based on a normal distribution as a data error distribution and p.d.f.

Assessment of lower extremity venous function using foot venous pressure measurement.

BACKGROUND: Measurement of foot venous pressure (FVP) is useful for evaluating chronic venous insufficiency (CVI) functionally, because CVI always causes venous hypertension. In the present study, the various FVP parameters were analysed according to the new classification of venous disorders based on clinical, aetiological, anatomical and pathophysiological data (the CEAP classification). METHODS: During the past 7 years, a total of 257 legs in 196 consecutive patients with CVI have been studied. The following FVP parameters were assessed: the percentage decrease in pressure from rest with manual calf compression, the rate of increase of pressure during 4 s after compression (4SR) and the time to 50 per cent recovery of pressure (RT50) after release of compression. RESULTS: The incidence of skin changes due to venous stasis increased as the percentage pressure drop and RT50 fell. In addition, a pressure drop of less than 72 per cent and an RT50 of less than 20 s could detect legs with skin changes with a sensitivity of 76 per cent and a specificity of 62 per cent. In legs with primary varicose veins, pressure drop, 4SR and RT50 values deteriorated in proportion to the severity of the associated deep venous reflux. CONCLUSION: FVP parameters correlate well with the severity of clinical manifestations and venous reflux, and could be used quantitatively to evaluate the severity of CVI.

Nephrotoxic effect of tris(2,3-dibromopropyl)phosphate on rat urinary metabolites: assessment from 13C-NMR spectra of urines and biochemical and histopathological examinations.

Rats received either single oral doses of 0, 25, 50, 100 and 200 mg/kg tris(2,3-dibromopropyl)phosphate (Tris-BP) or repeated doses of 50, 100 and 200 mg/kg/day Tris-BP for 7 days. Urine was collected over a 24-hr period and subjected to 13C-NMR and biochemical examinations. Tris-BP produced significant increases of urinary glucose and lactate. Urinary gamma-glutamyltransferase, lactate dehydrogenase and alkaline phosphatase levels were significantly elevated on the first 2 days of post-treatment. Histopathologically, the kidney exhibited proximal tubular damage at a dose of 200 mg/kg. There was a good correlation among the histopathological, biochemical results, and the 13C-NMR urinary metabolite fingerprints in the assessment of Tris-BP-induced renal damage. The abnormal patterns of metabolite excretion suggested that the lesions produced by Tris-BP were caused by changes in the metabolic function of tubular epithelial cells. The urinary excretion of lactate, enzymes and inhibition of glucose reabsorption from the tubular lumina may be attributed to necrosis and desquamation of the tubular cell.