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L Hothorn

Publications and source records attributed to L Hothorn.

7 recordsLinked to original sources
PubMed1994

Biostatistical analysis of the micronucleus mutagenicity assay based on the assumption of a mixing distribution.

The in vivo micronucleus assay can be analyzed by comparing the number of micronuclei (MN) of several dose groups with those of a control group. In several publications, difficulties arose in estimating a suitable distribution for MN, even in the untreated historical control groups. Mitchell et al. described the presence of a subpopulation of more susceptible responders. Based on this assumption of such a subpopulation, score tests were used for the mixing distribution of responders and nonresponders (behavior same as in untreated control animals) within the dose groups. The power behavior of these tests was characterized with a simulation study. The advantage of score tests can be shown, even in the practical and important guideline case of only five animals per group.

Animals↗
PubMed1994

Multiple comparisons in long-term toxicity studies.

Several multiple comparison procedures (MCPs) are discussed in relation to the specific formulation of type I and type II errors in toxicity studies and the typical one-way design control versus k treatment/dose groups. Examples for these MCPs are: the standard many-to-one MCP (Dunnett's procedure), sequential rejection modifications, closed testing procedures, many-to-one MCPs with an ordered alternative hypothesis, procedures based on the assumption of a mixing distribution of responders and nonresponders, and MCP's for multiple end points.

Hazardous Substances↗
PubMed1991

Tumor induction in a rat model for ureterosigmoidostomy without evidence of nitrosamine formation.

Twenty rats were randomized into a vesicosigmoidostomy and an unoperated control group. In both groups the 24 hour excretion of secondary amines, nitrate, nitrite and nitrosamines was measured before and after gavage of proline and nitrate, piperazine and nitrate, N-nitrosoproline, mono-N-nitrosopiperazine. The urinary nitrosamine concentrations were not significantly different between both groups neither before nor after application of the several substances. Thirty rats were randomized into two vesicosigmoidostomy groups with and without antibiotic coverage and an unoperated control group. After ligation of distal rectum and mesosigmoid the rectosigmoids were removed. No significant concentrations of volatile nitrosamines could be measured in the rectosigmoid contents of the three groups. One hundred and twenty rats randomized into three groups following vesicosigmoidostomy received the potential nitrosamine antidotes sodium-2-mercaptoethane sulfonate or sodiumpentosan-polysulfate or acted as controls. 12/118 (10.2%) developed adenomas and 25/118 (21.2%) adenocarcinomas at the vesico-colonic anastomosis with no significant differences between the three groups concerning tumor incidence or mortality. The results show that colon carcinomas occur in a rat model for ureterosigmoidostomy without evidence for thus induced nitrosamine formation. This and the missing effect of nitrosamine antidotes suggest that other factors than nitrosation must be responsible for colon carcinogenesis following urinary diversion via intestine.

Adenocarcinoma↗