EAU guidelines for the management of urogenital schistosomiasis.

More than 100 million people worldwide are affected by bilharziasis, caused by Schistosoma haematobium. For travellers precaution is most important. For the population in endemic areas, an integrated approach including health education is necessary. Effective pharmacologic treatment is available.

Heterogeneity in prostate cancer: prostate specific antigen (PSA) and DNA cytophotometry.

BACKGROUND: The heterogeneity in prostate cancer is the reason for the difficult diagnosis and prognosis of this tumor. In this study, we looked for a correlation between prostate specific antigen (PSA), tumor staging and DNA cytophotometry. MATERIALS AND METHODS: Twenty-two prostates (pT1-T4) from patients with prostate cancer, who underwent radical prostatectomy, were examined. Preoperative PSA and postoperative DNA image cytometry, after 2-8 needle biopsies out of each organ, were evaluated. RESULTS: The prostate cancer tissues showed, in DNA stemline-interpretation according to Fu, in homogenous diploid tumors an average PSA level of 3.8 ng/ml, and, in homogenous aneuploid tumors, a level of 14.0 ng/ml. Tumors with heterogeneous DNA patterns with a majority of aneuploidy had an average PSA level of 85.6 ng/ml, and heterogeneous tissues with a majority of diploidy a level of 10.9 ng/ml. CONCLUSION: Only the stemline-interpretation of Fu after DNA cytophotometry is efficient for diagnosis of prostate cancer, and allows prognostic statements of the disease.

Examination of tumorigenesis of precursor lesions in bladder cancer by in situ hybridization.

Through examinations using fluorescence in situ hybridization (FISH) of chromosomes 1 and 9, we tried to obtain more information on dysplasia and carcinoma in situ (Cis) in relation to the oncogenesis of bladder cancer. 63 paraffin sections (dysplasia grades I-III and Cis) were evaluated, and 8 negative sections functioned as a control group. For FISH, DNA samples of CEP 1 and 9 (alpha satellites) were chosen. Gains (aneuploidy) or losses (monosomy) of chromosomal material were determined microscopically. Dysplasia grades I-III showed a 5-18% aberration in chromosome 1 aneuploidy and a 19-29% aberration in monosomy 9. Cis revealed 27% aneuploidy of chromosomes 1 and 9. Although at present dysplasia grade III and Cis of the bladder are viewed as histopathologically identical, we examined both molecular genetic differences in chromosome 9. As referred to in the literature we found the same genetic aberrations for dysplasias (grades I-III) and noninvasive papillary bladder tumors as well as for Cis and solid invasive bladder cancer.

Stimulation of renal Na+ dicarboxylate cotransporter 1 by Na+/H+ exchanger regulating factor 2, serum and glucocorticoid inducible kinase isoforms, and protein kinase B.

Renal tubular citrate transport is accomplished by electrogenic Na(+) coupled dicarboxylate transporter NaDC-1, a carrier subjected to regulation by acidosis. Trafficking of the Na(+)/H(+) exchanger NHE3 is controlled by NHE regulating factors NHERF-1 and NHERF-2 and the serum and glucocorticoid inducible kinase SGK1. To test for a possible involvement in NaDC-1 regulation, mRNA encoding NaDC-1 was injected into Xenopus oocytes with or without cRNA encoding NHERF-1, NHERF-2, SGK1, SGK2, SGK3, and/or the constitutively active form of the related protein kinase B ((T308,S473D)PKB). Succinate induced inward currents (I(succ)) were taken as a measure of transport rate. Coexpression of neither NHERF-1 nor NHERF-2 in NaDC-1 expressing oocytes significantly altered I(succ). On the other hand, coexpression of SGK1, SGK3, and (T308,S473D)PKB stimulated I(succ), an effect further stimulated by additional coexpression of NHERF-2 but not of NHERF-1. The action of the kinases and NHERF-2 may link urinary citrate excretion to proximal tubular H(+) secretion.

Accuracy of the ImmunoCyt assay in the diagnosis of transitional cell carcinoma of the urinary bladder.

The ImmunoCyt assay (Diagnocure Inc., Québec, Canada) is a new immunocytological fluorescence test for identifying two different mucins and a high-molecular-weight glycosylated carcinoembryonic antigen (CEA) present in tumours originating from transitional epithelial cells. The test promises a higher diagnostic sensitivity in transitional cell carcinoma (TCC) of the bladder than voided urine cytology. Our study was designed to evaluate this test especially for TaG1 carcinomas, which are characterised by a low detection rate in urinary cytology. A total of 121 spontaneous urine samples of 92 patients (age range 28 to 86, mean 62.5 years) were examined. The samples were taken from patients suspected of having TCC (41 out of 121) or tumor recurrence (46 out of 121), or who were part of a follow-up protocol (34 out of 121). Cystoscopy was practiced in all patients. The ImmunoCyt test was carried out according to the manufacturer's protocol. For cytology cytospins were made from the same urine samples and stained according to the method of Papanicolaou. One hundred and thirteen specimens could be evaluated. In 87 cystoscopy and/or histology were negative. There was histological evidence of 7 pTaG1, 4 pTaG2, 8 pT1G2/G3 and 7 pT2G2/G3 TCC. As for ImmunoCyt and cytology, specificity was 83.9% and 91.9%, respectively. A combination of either test indicated 81.6% specificity. The sensitivity amounted to 38.5% and 34.6%, respectively, and the combined sensitivity to 53.8%. The sensitivity for TaG1 carcinomas was 14.3% each, for TaG2 carcinomas 25% and 50%, for T1G2/G3 carcinomas it amounted to 37.5% each, while for T2G2/G3 carcinomas it was 71.4% and 42.9%, respectively. The higher sensitivity of the ImmunoCyt test as compared to urinary cytology renders improved identification of exfoliated tumour cells in bladder cancer possible. In our study, however, the expected increase in detecting TaG1 carcinomas was not found. Because of its lower specificity, the test should only be used in combination with voided urine cytology. On account of its low sensitivity, the ImmunoCyt test cannot replace cystoscopy (with biopsy) in the diagnosis and monitoring of bladder cancer.

Comparison of cytology and nuclear matrix protein 22 (NMP 22) for the detection and follow-up of bladder-cancer.

OBJECTIVES: This study was designed to determine the clinical usefulness of the Nuclear Matrix Protein 22 (NMP 22) Test for the detection of bladder cancer in comparison to urine cytology. METHODS: One hundred sixty-four patients suffering from or being suspicious for bladder cancer and 64 healthy controls participated in a prospective study. Freshly voided spot urine samples were taken for cytological examination and determination of NMP 22-levels by enzyme-linked immunoassay. RESULTS: Sensitivity to the NMP 22 Test according to the tumor grading was (results of cytology in parentheses): GI 25.0% (20.0%), G2 68.2% (59.1%), and G3 100.0% (66.7%); overall sensitivity was 62.5% (45.0%). Sensitivity according to superficial bladder cancer was 46.7% (36.7%), and to invasive bladder cancer 90.0% (70.0%). Specificity was 65.9% (88.9%). CONCLUSIONS: NMP 22 is a reliable tool for detecting invasive bladder cancer. Results for the well-differentiated superficial bladder cancer occurring frequently are as poor as those obtained with cytology. In addition, benign lesions such as urolithiasis or urinary tract infection lead to false positive results. Therefore, cystoscopy has to be performed when trying to detect and follow-up bladder cancer.

[Physical and technical quality assurance and radiation protection in transperineal interstitial permanent prostate brachytherapy with 125-iodine seeds]. / Physikalisch-technische Qualitätssicherung und Strahlenschutz bei der Monotherapie der Prostata mit Jod-125-Seeds.

BACKGROUND: Early stage prostate cancer can be treated successfully by interstitial brachytherapy with 125-iodine seeds. A quality-assurance programme is presented that was designed for this purpose for internal clinical use. Furthermore the requirements of the new German Ordinance Governing Radiation Protection (StrlSchV) that came into force on August 1, 2001, are taken into account. MATERIAL AND METHODS: For the 125-iodine monotherapy of the prostate we used RAPID STRANDS (Amersham Health, Braunschweig, Germany). According to the guidelines of the new Ordinance Governing Radiation Protection, the determination of the body dose of the staff is made to rely on the new measurement quantities H(p) (10) and H(p) (0.07). The nominal air kerma rate of the seeds is measured with a calibrated well-chamber of the type HDR 1000 Plus and an electrometer of the type MAX 4000 (Standard Imaging Inc., USA). The ultrasound images of the prostate are produced by an ultrasound device of the type Falcon 2101 (B-K Medical, Denmark). For treatment planning the programme VariSeed (Varian, Darmstadt, Germany) was employed. Correct loading of the needles is controlled by autoradiography before implantation. After the implantation radiation-protection measurements in the operating room are carried out. RESULTS: As regards the personnel, for the depth personal dose equivalent Hp(10) and relating to two applications each, measurement values between 0 microSv and 14 microSv resulted. The control of the radiation exposure of the hands revealed superficial personal dose values H(p) (0.07) of up to 1 mSv. The nominal air kerma rates of the RAPID STRANDS were all lying within the 95% confidence interval guaranteed by the producer. The autoradiographs documented -- except for one case -- the correct loading of the needles. The interstitial transperineal prostate implantation of the 125-iodine seeds succeeded as planned with all patients. Until now no contamination of the operating room was detected by the radiation-protection measurements. CONCLUSION: The physical-technical quality assurance programme presented here covers the whole physical-technical range of the internal clinical quality assurance and could be integrated into the course of the treatment without any problems. It has th following advantages: The autoradiographic documentation of the correctly loaded needles serves as proof that the prerequisite for the production of the prescribed physical dose distribution is fulfilled. The internal clinical determination of the nominal air kerma rate is the basis for a correct dose application.

Genomic and functional investigations of mutations of the SLC3A1 gene in cystinuria.

BACKGROUND: Cystinuria is the second most frequent autosomal recessively inherited disorder in Europe, and it is based on a disturbance of the transepithelial transport of cystine and amino acids in the proximal renal tubule as well as in the intestinum. From the point of view of the urologist, patients suffering from cystine stones represent an important population because they develop a great number of recurrences which necessitate frequent stone removal. METHODS/RESULTS: Advances in the field of molecular genetics have rendered it possible to correlate genotype and phenotype of these patients. In the candidate gene, the SLC3A1 gene, 25 mutations in patients suffering from cystinuria have been described so far. Investigations in our patients (n = 15) as well as results obtained by other study groups have revealed an average detection rate of approximately 50%. The low rate as well as in-depth physiological analyses of the individual mutations indicate that the SLC3A1 is a subunit of a heteromeric complex. This supposition is supported by the structure of the transporter as well as by biochemical analyses of the urine of cystinuric patients and their relatives. Investigations on other genomic segments and candidate genes localized there are being performed. However, it has already appeared that cystinuria is not based on alterations of one single gene, but that a variety of factors combine in the development of this disease. CONCLUSIONS: To be able to offer a molecular genetic diagnosis for patients suffering from cystinuria, the search for mutations of the SLC3A1 gene is being expanded and a screening for other candidate genes set up which are designed to early recognize the risk factors of cystinuria as well as to be able to initiate early therapy.

Integrated functional genomics approach for the design of patient-individual antitumor vaccines.

Our aim is to identify as many candidates as possible for tumor-associated T-cell epitopes in individual patients. First, we performed expression profiling of tumor and normal tissue to identify genes exclusively expressed or overexpressed in the tumor sample. Then, using mass spectrometry, we characterized up to 77 different MHC ligands from the same tumor sample. Several of the MHC ligands were derived from overexpressed gene products, one was derived from a proto-oncogene, and another was derived from a frameshift mutation. At least one was identified as an actual T-cell epitope. Thus, we could show that by combining these two analytic tools, it is possible to propose several candidates for peptide-based immunotherapy. We envision the use of this novel integrated functional genomics approach for the design of antitumor vaccines tailored to suit the needs of each patient.

[Physical basics and clinical realization of interstitial brachytherapy of the prostate with iodine 125]. / Physikalische Grundlagen und klinische Durchführung der interstitiellen Brachytherapie der Prostata mit Jod-125.

BACKGROUND: Interstitial brachytherapy with I-125 seeds can be used for successful treatment of early stage prostate cancer. There is presented the technique of permanent transperineal implantation of I-125 seeds with intraoperative treatment planning which is suited for the treatment of prostate cancer up to the clinical stage of T2a. MATERIAL AND METHODS: Some weeks before the implantation of the seeds the prostate volume is determined using transrectal ultrasound (TRUS) so as to estimate the required number of I-125 seeds. At the outset of the treatment the prostate is stabilized by two perineally inserted needles. Subsequently there is carried out an ultrasound guided treatment planning that allows to optimize the distribution of the seeds within the prostate. In interstitial brachytherapy we use RAPID STRANDS((R)), i. e. the I-125 seeds are embedded in vicryl suture at distances of 1 cm. During implantation of the I-125 seeds the transversal placement of the applicator needles is controlled by TRUS and the cranio-caudal placement of the applicator needles is controlled using the fluoroscopic unit as well as TRUS. About 4 weeks after the implantation of the seeds there is carried out a postoperative computation of the dose distribution of the implant using CT imaging. RESULTS: The procedure possesses the advantage that ultrasound imaging, treatment planning and seed implantation are carried out with the prostate remaining in an unaltered position. During implantation the combined imaging of TRUS and fluoroscopy allows a safe placement of the seeds with in the prostate. CONCLUSION: The methods for the calculation of the actually attained dose distribution must still be optimized, because the postoperative examination of the individual results has so far been possible only with difficulties resulting from methodological inconveniences.

Selenium reduces high energy shock wave-induced renal injury in rats.

Using an in vitro model with Madin-Darby canine kidney (MDCK) cells, we showed that shock wave-induced renal injury could be ameliorated by selenium. We examined the influence of selenium, a free radical scavenger, in shock wave-induced tubular cell injury in vivo. Male rats were randomly assigned to three groups: 1 control (n= 18), 2 selenium (n = 18), 3 sham treatment (n = 4). Groups 1 and 2 were treated with 500 shock waves on each kidney. Animals assigned to group 3 (sham treatment) received only anesthetics. Selenium (80 microg/kg per 24 h intraperitoneally) was given to the animals in group 2 for 5 days, starting 1 day before shock wave exposure. Urine was collected for 8 h on the day before and immediately, 1, 7 and 28 days after shock wave exposure (SWE) for the measurement of urine volume, N-acetyl-beta-glucosaminidase (NAG), beta-2-microglobulin (beta2 M), and creatinine. Blood was taken from these rats on day 1 after SWE for the determination of creatinine and the calculation of the creatinine clearance (CCr). After SWE, there was a significantly increased diuresis in group 1 and 2. The excretion of NAG and beta2 M was also increased in both groups. These changes were significantly less pronounced in the selenium treated rats. CCr was higher in the selenium group than in the controls. No changes were observed in the sham treated group. These results demonstrate that selenium is able to ameliorate the damaging effects of high energy shock waves on renal tissue not only in vitro, but also in vivo.