Analysis of epidemiological cohort data on smoking effects and lung cancer with a multi-stage cancer model.

A stochastic two-stage cancer model is used to analyse the relation between lung cancer and cigarette smoking. The model contains the main rate-limiting stages of carcinogenesis, which include initiation, promotion (clonal expansion of initiated cells), malignant transformation and a lag time for tumour formation. Various data sets were used to test the model. These include the data of a large prospective collaborative project carried out in 10 different European countries, the European Prospective Investigation into Cancer and Nutrition (EPIC). This new data set has not been modelled before. The model is also tested on other published data from CPS-II (Cancer Prevention Study II) of the American Cancer Society and the British doctors' study. The analyses indicate that the EPIC data are best described with smoking dependence on the rates of malignant transformation and clonal expansion. With increasing smoking rates, saturation effects in the two exposure rate-dependent model parameters were observed. The results find confirmation in the biological literature, where both mutational effects and promotional effects of cigarette smoke are documented.

Food and nutrient intake, anthropometric measurements and smoking according to alcohol consumption in the EPIC Heidelberg study.

AIMS: The study was carried out to determine associations of reported alcohol intake with dietary habits, body mass index, waist-to-hip ratio (WHR) and smoking. SUBJECTS AND METHODS: 24,894 subjects who participated in the baseline examination of the German part of the European Prospective Investigation into Cancer and Nutrition (EPIC) in Heidelberg and were between 35 and 65 years of age at baseline were included in the present cross-sectional analysis (11,617 men, 13,277 women). Diet and alcohol consumption were assessed with a semiquantitative food frequency questionnaire. Analysis of covariance with age as a covariate was used to analyse the association between alcohol intake and dietary consumption patterns, BMI, WHR and smoking. RESULTS: Alcohol did not replace other food items, but was an addition to the diet. Among alcohol consumers, fat and protein intake as a percentage of energy was slightly higher and carbohydrate intake was slightly lower than among abstainers. Alcohol consumers had a lower intake of fruits, dairy products, cereal products, and added vegetable fat and a higher intake of animal products such as meat, fish, eggs and added animal fat than abstainers. The prevalence of current smoking showed a U-shaped relation to alcohol intake in men and women. In men, a U-shaped association was also seen between the prevalence of former smoking and alcohol intake, while the prevalence of former smoking increased linearly with alcohol intake in women. CONCLUSION: The results show that alcohol consumption is associated with dietary consumption patterns and smoking. Therefore, it will be important to consider dietary patterns and other lifestyle parameters when investigating the health effects of alcohol intake in the future.

Effects of FK-506 on the course of murine salmonellosis.

Bacterial infections are a major threat to immunocompromised patients. Therefore, the effect of immunosuppression with cyclosporin A and FK-506 on the course of murine salmonellosis was tested. Treatment of mice with both substances reduced the amount of circulating CD4+ T-cells and CD8+ T-cells in uninfected and infected mice. The substances effectively suppressed the proliferation of spleen cells of treated mice upon activation with concanavalin A (ConA) and upon activation by mouse peritoneal macrophages infected with live salmonellae, but left the response to lipopolysaccharide (LPS) unaltered. In particular, treatment of mice with nontoxic doses led to an increase in Salmonella typhimurium counts in the organs of primarily infected mice from day 14 onward, but not in the early phase of infection. In mice treated during secondary infection with S. typhimurium the bacterial counts in the organs were increased from day 3 of infection onward. We conclude that both substances aggravate murine salmonellosis, most likely by inhibition of T-cell function. Patients receiving FK-506 might also be, therefore, at risk of salmonella infection.

Fitting response curves for radioimmunoassays or immunoradiometric assays.

The paper describes non-linear regression methods for the evaluation of radioimmunoassay or immunoradiometric assay data. The underlying model is an overdispersed Poisson process with four regression line parameters and one parameter related to the overdispersion of the variance. A generalized least-squares algorithm is described for the parameter estimation of non-contaminated data. In the presence of outliers in Y-direction, the results are improved by a winsorized version of the generalized least-squares method.

[Individual prognosis in gastroduodenal ulcer hemorrhage: practical application]. / Individuelle Prognostik bei der gastroduodenalen Ulcus-Blutung: Praktische Anwendung.

Using modern methods of medical decision making (regression analysis) one can determine risk factors for rebleeding in peptic ulcer disease. Prediction of rebleeding for the individual patient is possible. Under regard of five effective risk factors and using adequate statistical methods, sensitivity and specificity reach about 80%.

Ovarian carcinoma: increase in clinical validity by simultaneous determination of SRA and CA 125.

Ovarian carcinomas are distinguished by their polyclonality, i.e., heterogeneity and polymorphism of their tissue. There is no marker available complying with the clinical demands in the case of ovarian carcinoma regarding satisfactory sensitivity and specificity. Therefore, we have simultaneously determined two entirely distinct tumor markers, serum ribonuclease activity (SRA) and cancer antigen 125 (CA 125), recommended in the literature with respect to ovarian carcinoma. After evaluation by logistic regression analysis, we found a specificity of 93% together with a sensitivity of 97% for the simultaneous determination of SRA and CA 125 (37 ovarian carcinomas, 11 cases without pathological findings after treatment, 11 benign tumors of the ovary, 61 controls). The patients are not exposed to increased stress by this simultaneous determination method compared to the determination of a single marker. The increased clinical validity justifies the recommendation of routine simultaneous determinations of SRA and CA 125 for diagnosis and monitoring of patients with ovarian carcinoma.

Randomized crossover study of the antiemetic activity of levonantradol and metoclopramide in cancer patients receiving chemotherapy.

In a randomized crossover study 57 cancer patients receiving chemotherapy with high emetic potential were treated with low-dose levonantradol or standard-dose metoclopramide and crossed over to the other antiemetic drug in the next identical chemotherapy cycle. In the 45 patients evaluable for treatment response the antiemetic efficacy of levonantradol was significantly better: 62% had less nausea and 58% less vomiting, as against 11% and 16%, respectively, with metoclopramide. Patient preference for antiemetic treatment was levonantradol in 49% and metoclopramide in 22% of cases. Levonantradol treatment was accompanied by a relatively high incidence of side-effects (71%) compared with metoclopramide (29%). The antiemetic efficacy of each single drug was incomplete in most cases of this trial, and antiemetic combination therapy is recommended for further trials.