The clonality of synchronous and metachronous bladder tumors has been studied for years with controversial results. Some recent studies support the 'polyclonal origin' hypothesis, i.e. that independently transformed different tumor cell clones exist in the same bladder cancer patient and arise from the field cancerogenisation affecting the entire bladder urothelium by environmental mutagens. Others could demonstrate a monoclonal origin of primary bladder tumors and its recurrences due to a single genetically transformed cell clone spread through the urinary system. With increasing understanding of the clonal origin of bladder tumors and recurrences, clonality markers might contribute to an early and accurate prediction of tumor recurrence and progression. We used p53 mutations as an identification marker permitting the prediction of clonality in bladder tumors and its recurrences. Primary tumors (n=33) and recurrences (n=63) were screened by direct genomic sequencing the p53 mutation hot spot region, exons 5-8. P53 mutations occurred in 12% in our cohort, predominantly in higher malignant (>or=G2), invasive (>or=T1) tumor samples. We were able to demonstrate intratumoral heterogeneity regarding the p53 status and that recurrences may occur from genetically unrelated primary tumor sites. Some of our results argue for a polyclonal origin of synchronous and metachronous bladder tumors possibly due to the field effect in bladder carcinogenesis. Evidence for a monoclonal origin was found in two cases: one case with a high malignant primary tumor and 3 metachronous recurrences, all of them harbouring the same exon 8 mutation found in the primary tumor; one case with identical mutations of exon 8 in the primary and one recurrent tumor. For further implications concerning clonality of recurrent bladder tumors, p53 status should be combined with a broader range of markers such as CGH and LOH pattern.

Fluorescence diagnosis of superficial bladder cancer using 5-aminolevulinic acid (ALA) is a highly sensitive technique (95%). However, the specificity is only 60-70% due to false-positive results after histopathological examination. We hypothesized that the biopsies in fluorescence endoscopy could represent early preneoplastic lesions not detectable by histopathology. In order to evaluate the specificity of fluorescence endoscopy at the molecular genetic level we performed comparative genomic hybridization (CGH) and investigated telomerase activity of ALA-positive tissue samples. For CGH, DNA was isolated from 5-10 frozen sections. Tumor and normal (control) DNAs were amplified by DOP-PCR and labeled with biotin-dUTP and digoxigenin-dUTP, respectively. Hybridization and detection were carried out according to standard protocols. Telomerase activity was analyzed using a non-radioactive system (TRAP-assay). In 33 out of 118 bladder cancer cases (28%) detected by conventional cystoscopy, additional suspicious areas were found using ALA. CGH revealed genetic changes in 27% of samples with non-malignant histological diagnoses. Telomerase activity was found in 59% of these samples. Tumor samples showed genetic alterations in 84% and in 69% telomerase activity occurred. The type of genetic alterations in the normal biopsies was identical to the tumors. Based on these molecular data, the portion of false-positive results obtained by fluorescence diagnosis is lower than defined by histopathology alone. Genetic alterations and activation of telomerase activity are early events of tumor development in bladder cancer occurring earlier than histological features of neoplasia. The clinical importance of fluorescence diagnosis and the possible reduction of the recurrence rate have to be shown in ongoing clinical studies.

Abstract: Six microsatellite markers were selected to detect shifts or loss of heterozygosity (LOH) in urine, serum, and plasma samples of 44 bladder cancer patients. After centrifugation at 15,000g, we used supernatants for DNA analysis only. Tumor specimens were obtained by transurethral resection (TUR). Genetic alterations were detected in 33 of the 44 bladder tumors (75%). After polymerase chain reaction (PCR), DNA was detectable in 96% of all body fluid samples. Twenty‐six percent of the detected microsatellite alterations of free DNA were tumor‐specific, but 82% of all microsatellite changes of the tumors could be detected in body fluids. The study indicates that the simultaneous and multiple investigations of highly specific microsatellite markers could have a clinical relevance as a noninvasive tool for diagnosis and screening of bladder cancer. However, new ways for the sensitive DNA isolation of body fluids are needed.

Key words: acute tubular necrosis, nucleoside tri-spectrum of two patients with cyclosporin A damage was not altered compared to the controls. Conclusions. 31P-MRS can be used in patients in the early period after renal transplantation. A significant correlation between the PME/PDE ratio and the time course but no change in the b-NTP concentration was found in patients with primary allograft function in Abstract the first 4 weeks after renal transplantation. Different Background. 31P-Magnetic resonance spectroscopy patterns of 31P-MR spectra were observed depending (31P-MRS) can be used as a non-invasive tool for on the different causes of primary and early transplant measuring the relative intracellular concentrations of dysfunction. several phosphorus metabolites in different organs. Various pathological conditions are characterized by different metabolic patterns. We studied the value of Introduction 31P-MRS after renal transplantation with both an uneventful and a clinically complicated course. Primary and early allograft dysfunction remains a Methods. We determined the relative concentrations challenge for the nephrologist. A rapid diagnosis is of phosphate-containing metabolites in renal allografts necessary, because a delay in treating early rejection of humans with 31P-MRS (1.5 Tesla) in the first few deteriorates the prognosis of the allograft function. On weeks after transplantation; 18 patients with an the another hand, the immediate anti-rejection treat-uneventful clinical course and 10 patients who required ment based on a mere clinical suspicion of rejection dialysis after transplantation were examined. Six alone endangers those patients who have a delayed patients with a stable allograft function 2–3 months graft function caused by an acute tubular necrosis after transplantation served as controls. (ATN) or a cyclosporin A (CSA) damage through Results. In patients with primary allograft function, possible side effects of anti-rejection treatment. The we found a significant correlation between the phos-only reliable method for recognizing the cause of phomonoester/phosphodiester-ratio (PME/PDE) (r= primary transplant dysfunction is the invasive trans-0.66, r<0.01) and the time after transplantation, but plant biopsy. The diagnostic value of non-invasive no correlation between the nucleoside triphosphate (b-procedures–sonography and scintigraphy–is limited to NTP)-concentration (r=−0.11) and the time course. providing the accurate diagnosis in such cases [1]. In the patients with primary or early allograft dysfunc-Colour Doppler sonography is an improvement in tion caused by histologically proven rejection (n=5), diagnostic management after renal transplantation, we found a low b-NTP compared to patients with especially for vascular complications. However, the an uncomplicated clinical course (0.09±0.01 vs measurable alterations of the vessel indices as …

Ein vonLöns als blutmäßiger Vater ermittelter Beklagter wird durch die Rh-Untergruppenbefunde ausgeschlossen. Dieser Fall ist besonders in Anbetracht der oben zitierten Ausführungen vonHompesch geeignet, die Beweiskraft desLöns-Testes wesentlich zu erschüttern.

Zunächst wird an Hand der einschlägigen Literatur gezeigt, daß schon seit 1890 Hefe mit Erfolg als Fleischersatzstoff für bakteriologische Nährböden benutzt wurde. Seit dem Aufkommen von Hefeextrakten besserten sich die Resultate. Von manchen Autoren wurde darauf hingewiesen, daß den Hefeextraktnährmedien keineswegs der Makel des “Ersatz”stoffes anhafte, sondern daß diese Nährsubstrate den Fleischwassernährböden teilweise sogar überlegen seien. Dennoch bürgerten sich die Hefeextraktnährmedien bisher in der praktischen Bakteriologie der Medizinaluntersuchungsämter noch nicht ein. Wir fühlten uns auf Grund dieser Tatsache veranlaßt, von uns aus nochmals eingehend die Brauchbarkeit der Hefeextraktmedien in der diagnostischen Bakteriologie experimentell nachzuprüfen und kamen zu folgendem Resultat:

In den Monaten August–September 1948 kam es zu einer 49 Krankheitsfälle umfassenden Paratyphus B-Epidemie in den Kreisen Dillenburg, Wetzlar und Biedenkopf, die ihren Schwerpunkt in der Gemeinde Sinn (Dillkreis) hatte und eindeutig als Speiseeisinfektion geklärt werden konnte. Die von dem Keimträger Bäckermeister F. ausgeschiedenen Paratyphusbakterien gelangten über die Abortanlage in den Hausbrunnen, dessen Wasser ohne Erhitzung zur Speiseeiszubereitung benutzt wurde.