TP53 mutation profile in chronic lymphocytic leukemia: evidence for a disease specific profile from a comprehensive analysis of 268 mutations.

The TP53 mutation profile in chronic lymphocytic leukemia (CLL) and the correlation of TP53 mutations with allele status or associated molecular genetics are currently unknown. We performed a large mutation analysis of TP53 at four centers and characterized the pattern of TP53 mutations in CLL. We report on 268 mutations in 254 patients with CLL. Missense mutations appeared in 74% of cases compared with deletions and insertions (20%), nonsense (4%) and splice site (2%) mutations. The majority (243 of 268) of mutations were located in the DNA-binding domain. Transitions were found in 131 of 268 mutations, with only 41 occurring at methylated CpG sites (15%), suggesting that transitions at CpGs are uncommon. The codons most frequently mutated were at positions 175, 179, 248 and 273; in addition, we detected a common 2-nt deletion in the codon 209. Most mutations (199 of 259) were accompanied by deletion of the other allele (17p-). Interestingly, trisomy 12 (without 17p-) was only found in one of 60 cases with TP53 mutation (without 17p-) compared with 60 of 16 in the cohort without mutation (P=0.006). The mutational profile was not different in the cohorts with and without previous therapy, suggesting that the mechanism underlying the development of mutations may be similar, independent of treatment.

[Statistical evaluation of residue data for the assessment of predicted values (half-life, withdrawal time) as an example of toltrazuril and enrofloxacin in trout]. / Statistische Auswertung von Rückstandsdaten zur Absicherung von Vorhersagewerten (Halbwertzeit, Wartezeit) am Beispiel von Toltrazuril- und Enrofloxacin-Rückständen in Forellen.

The half-lives and withdrawal times of the veterinary drugs Toltrazuril and Enrofloxacin in trout have been assessed by statistical analysis. Confidence intervals were computed using a normal distribution of residual data and an empirical distribution by the Bootstrap method. Both methods produced similar statistics for the two drugs. Simulation of the residue data according to the regression lines of the decay curves has shown that the Bootstrap method is better for use when the residue patterns are not distributed normally. Using confidence intervals, a statistical mean of withdrawal times can be assessed. Taking into account the decays of the individual antibiotics in all treated trout, tolerance intervals for the regression lines are obtained: the calculated 10-20% longer withdrawal time includes values for which the antibiotic concentration in 95% of the treated trout is decreased below the tolerance level of Toltrazuril or Enrofloxacin.

Role of nocturnal acid suppression on the rate of duodenal ulcer healing: clinical dose-range trials with oxmetidine.

These studies represent the first attempt to compare, concurrently, several once or twice daily dosage regimens of an H2-receptor antagonist for ulcer-healing efficacy in the same national population within the same time period, using the same criteria for patient selection, duration of treatment, and end-point. Investigators from 66 centers entered 745 patients, 17-71 years of age, with endoscopically documented uncomplicated duodenal or pyloric channel ulcers, greater than or equal to 0.5 cm in the longest axis. Patients were randomly assigned to six regimens (five oxmetidine, one placebo) and were dosed once (bedtime) or twice (morning and bedtime) daily. Antacid use was restricted. Endoscopy was performed at wk 0 and 2, and at wk 4 in patients not healed at wk 2. Statistical analysis at wk 4 revealed the following healing rates with oxmetidine: 400 mg bid-73.3%; 600 hs-71%; 400 hs-68.6 and 61.6%; 200 mg bid-61.5%; and 200 hs-59.9%. All of the regimens except 200 hs were statistically significantly superior to placebo. The efficacy of the nocturnal 600-mg dose was comparable to that of 400 mg bid and the efficacy of the nocturnal 400-mg dose was comparable to that of 200 mg bid.

Vocal indicators of psychiatric treatment effects in depressives and schizophrenics.

Voice and speech changes as a result of clinical treatment for 17 depressive and 15 schizophrenic patients were investigated. Speech samples taken at interviews before and after treatment were analyzed with regard to f0, spectral energy distribution, and formant frequencies of vowels occurring in identical phonetical context. Both groups of patients showed a decrease in f0 after therapy, which was interpreted as a reduction of general arousal. Differential results with regard to spectral energy distribution suggested that the voice of depressives became more relaxed after therapy, but the opposite seemed to be true for schizophrenics. Significant formant changes obtained for the first formants of two vowels were interpreted as differences in the precision of articulation before and after therapy.