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Biomedical subjects

M Stöckle

Publications and source records attributed to M Stöckle.

At least 55 records · Page 3Linked to original sources

Malaria infection and morbidity in infants in relation to genetic polymorphisms in Tanzania.

To investigate the effects of host polymorphisms on malaria morbidity and infection, the frequency distributions of TNF alpha promotor gene and sickle cell trait were studied in infants in an area highly endemic for Plasmodium falciparum transmission in Tanzania. Differences in parasite prevalence, density, febrile episodes with and without parasitaemia, PCV levels and the frequencies of different MSP-2 parasite infections were assessed by genotype. The frequency of the TNF alpha promotor allele 2 was 0.09, and the trait was in Hardy-Weinberg equilibrium. There were no differences in malariametric indices between infants with the normal TNF alpha promoter gene and those who were heterozygous for this trait. Infants heterozygous for the TNF alpha promotor gene appeared to have fewer febrile episodes when they were free of parasites. The two infants homozygous for the TNF alpha promoter allele 2 had both a much higher incidence of fever, independently of parasitaemia, than the average for the other genotypes. The frequency of the sickle cell allele S was 0.06 and the trait was also in Hardy-Weinberg equilibrium. Infants heterozygous for the sickle cell trait had significantly lower parasite densities, but similar prevalence, and MSP-2 infections compared to infants with normal haemoglobin. PCV levels, and the incidence of febrile episodes both with and without parasitaemia were also similar. In contrast to the sickle cell trait, the TNF alpha promotor polymorphism appeared not to have any protective effect on malaria in this study, and its importance in other unspecified fever-causing diseases in this population needs further investigation.

Alleles↗

Differential mucin MUC7 gene expression in invasive bladder carcinoma in contrast to uniform MUC1 and MUC2 gene expression in both normal urothelium and bladder carcinoma.

Mucins (MUCs) are high molecular weight membrane glycoproteins. The gene expression of MUCs (MUC1-MUC8) may change characteristically during malignant transformation of epithelial tissues. Total RNA was isolated from the four bladder cancer cell lines RT4, 647V, HT1376, and 486P (pathological gradings between G1 and G4) and 17 samples of transitional cell carcinomas, as well as 16 samples of normal human urothelium of the bladder from surgically removed specimens. The RNA samples were studied with MUC1-, MUC2- and MUC7-specific nested reverse transcription-PCRs. Gene expression of MUC1 and MUC2 was found positive in all normal, as well as in malignant, tissue samples and in the tumor cell lines. In contrast, gene expression of MUC7 was only detected in bladder cancer cell lines and samples of invasive transitional cell carcinomas, but neither in superficial, noninvasive bladder tumors nor normal bladder urothelium. Only one of the samples of normal urothelium obtained from 16 different tumor-bearing bladders was positive for MUC7 gene expression. These results suggest a differential MUC7 gene expression with the onset of malignant transformation of the bladder urothelium.

Carcinoma, Transitional Cell↗

Brachytherapy in localized prostatic cancer: 100 years of radium.

Contemporary series of brachytherapy in localized prostate cancer show promising early results attributable to improved patient selection and technical refinements in treatment modalities. These innovations consist essentially of precise three-dimensional radioactive dose-distribution planning and source placement, thus solving the problem of possible under-dosage encountered in open brachytherapy.

Journal Article↗

Urinary leakage of tubular enzymes after shock wave lithotripsy.

OBJECTIVES: Urinary loss of tubular marker enzymes following shock wave lithotripsy (SWL) suggests corresponding morphological changes in the kidney. To date, the morphological correlate of enzymuria and its dependence on the energy applied remains unclear. METHODS: In an animal study, the acute morphological changes occurring in the tubulus cells as the basis of enzymuria were investigated. It was evaluated whether SWL-induced enzymuria correlates with the extent of renal damage. RESULTS: Acute morphological changes in the tubulus cells were demonstrated beneath isolated tubulus necrosis. The mechanically induced lesions of the cell organelles included fragmentation of the lysosomes and severe alterations of the cell membrane. The tubulus damage can be quantified. With the help of histochemical N-acetyl-beta-D-glucosaminidase (NAG) staining and electron microscopic observations, a significant correlation was found between the shock wave parameters number of impulses and intensity and the tubular damage. The intensity of NAG enzymuria reflected the severity of the tubular damage. CONCLUSIONS: In this animal model, NAG proved to be a suitable marker enzyme for estimation of the degree of SWL-induced tubular damage.

Acetylglucosaminidase↗

Detection of deletions in the short arm of chromosome 3 in uncultured renal cell carcinomas by interphase cytogenetics.

PURPOSE: Analysis of genetic alterations may facilitate the differential diagnosis of renal cell carcinoma (RCC) subtypes. For genetic classification, deletion of the short arm of chromosome 3 (3p), the hallmark of nonpapillary/clear cell RCC, is a major diagnostic criterion. Because of the limited routine applicability of cytogenetics and molecular genetic techniques we investigated interphase fluorescence in situ hybridization (FISH) for the detection of this aberration in RCC. MATERIALS AND METHODS: Using seven chromosome 3 specific probes FISH was performed on isolated nuclei from 26 uncultured sporadic RCC. RESULTS: Alterations of chromosome 3 were identified in 19 RCC (73%). Monosomy and/or 3p-deletions were observed in 15 of 19 (79%) non-papillary/clear cell RCC but not in other morphologic subgroups. The median percentage of cells in a specimen containing loss of 3p was 45%. Deletion mapping indicated that large deletions affecting different regions in 3p are predominant. Chromosomal region 3p24 was recurrently involved in all RCC with a deletion in 3p. CONCLUSION: Interphase FISH for the detection of loss in 3p provides a sensitive and feasible method for the genetic classification of kidney tumors and the delineation of recurrently deleted regions in 3p.

Adult↗

Involvement of the chromosomal region 11q13 in renal oncocytoma: case report and literature review.

Renal oncocytomas comprise a cytogenetically heterogeneous group of tumors consisting potentially of cytogenetic distinguishable subgroups. Review of the literature revealed loss of chromosome 1 and Y as a possible anomaly for at least one subset oncocytomas. The frequent finding of rearrangements involving chromosome 11 band q13 characterizes another subset of oncocytomas. We report the cytogenetic and pathological features of a renal oncocytoma diagnosed in a 72-year-old woman and found a t(9;11)(p23;q13) as a consistent abnormality. This supports the idea that translocations involving 11q13 define a further subset of oncocytoma.

Adenoma, Oxyphilic↗

Treatment of patients with bladder exstrophy or incontinent epispadias. A long-term follow-up.

OBJECTIVE: To determine the late outcome concerning urinary continence, late complications, sexuality, and fertility in patients with the exstrophy-epispadias complex. METHODS: Until July 1994, 115 patients underwent surgical treatment at our institution. The mean follow-up period in 102 patients is 16.7 years. Urinary diversion was performed in 88 patients, a modified Young-Dees procedure in 8, a sling plasty in 3, and genital reconstruction alone in 3 patients. RESULTS: The present continence rates are 96% for rectal reservoirs, 97% for Mainz pouch 1, and 67% for the modified Young-Dees procedure. The upper tracts have remained stable, and no bowel neoplasms have developed. 16 of 17 women > or = 18 years of age are satisfied with the cosmetic result after genital reconstruction. All adults engage in sexual intercourse; 5 women have delivered 7 children by cesarean section. 30 of 32 male adults are satisfied with the cosmetic result of the reconstructed external genitalia. Penile deviation was present in 11, distressing in 2 patients. After genital reconstruction 9 developed epididymitis, necessitating 2 orchiectomies and 3 vasectomies. No patient with reconstruction of the external genitalia can ejaculate normally or has fathered children, whereas the ejaculation was normal in 3 who did not undergo genital reconstruction. Furthermore, 2 of the 5 have fathered 4 children. CONCLUSIONS: Rectal reservoirs represent our urinary diversion of choice. After failed reconstruction/insufficient anal sphincter, a Mainz pouch I is constructed. The cosmetic results achieved by genital reconstruction are satisfactory. In women, antefixation of the uterus should be performed before or together with an introitus plasty to prevent uterine prolapse. In men, however, surgery is performed at the expense of fertility.

Adult↗

Automated image analysis DNA cytometry to predict the pathological stage in clinical stage I nonseminomatous testicular germ cell tumors.

OBJECTIVE: Automated image analysis DNA cytometry was used to predict the pathological stage in clinical stage I nonseminomatous testicular germ cell tumor patients. METHODS: Orchiectomy specimens of 74 patients (41 pathological stage I, 33 pathological stage II) were analyzed by modular image analysis computer, and several mathematical indices from the DNA histogram were calculated. RESULTS: The 5c-exceeding rate (rate of hyperpentaploid nuclei) was found to be significantly higher in patients with pathological stage II disease as compared with patients without metastases (p = 0.0174). Tumor tissue from lymph node metastases showed even higher amounts of hyperpentaploid nuclei (p < 0.0005). In this study, all patients with a 5c-exceeding rate above 3.1% had metastatic disease. CONCLUSIONS: Single-cell cytophotometry was able to show significant differences in 5c-exceeding rates between patients with and without tumor metastases. Because of high standard deviations, however, it was not possible to use this parameter for correct staging in all patients.

Analysis of Variance↗

Social integration, sexual behavior and fertility in patients with bladder exstrophy--a long-term follow up.

UNLABELLED: After primary bladder closure or urinary diversion, other factors apart from the reconstruction itself gain importance for individuals with the exstrophy-epispadias complex: social integration and, after reaching puberty, sexuality and fertility. Between 1968 and July 1994 115 patients with bladder exstrophy or incontinent epispadias underwent surgery at our institution. A total of 104 patients could be followed, 2 of whom died in the meantime. Of the remaining 102 patients 48 attend school, 4 are in college, 40 have completed or are currently undergoing vocational training, 3 are unemployed, 1 lives in a therapeutic centre and 6 are younger than 6 years of age. A total of 95% of the patients with continent urinary diversion are continent day and night, whereas only three of five patients with a sling plasty (incontinent epispadias) or with primary bladder closure followed by a Young-Dees procedure are continent. None of the patients showed deterioration or renal function. In 25 females the external genitalia were reconstructed. Fixation of the uterus was done in 13 to correct or prevent uterine prolapse. Of the 17 women older than 18 years of age with genital reconstruction, 16 are satisfied with the cosmetic result. All adults engage in sexual intercourse. Five women have delivered seven children by Caesarean section. Of the 35 male adults 32 underwent reconstruction of the external genitalia and 34 males achieve erection. One developed necrosis of the penis early in life following primary bladder closure performed at an outside hospital. Penile deviation was present in 11 of the 32 patients with genital reconstruction, which is distressing in only 2. Thirty patients are satisfied with the cosmetic result. After genital reconstruction 9 males developed epididymitis, necessitating two orchiectomies and three vasectomies. No patients with reconstruction of the external genitalia can ejaculate normally or has fathered children, whereas ejaculation was normal in the three men who did not undergo genital reconstruction and in two patients prior to post-pubertal reconstruction. Furthermore, two of these three men have fathered four children. CONCLUSION: Education, occupation and social development of patients with urinary diversion are uneventful. The cosmetic results achieved by genital reconstruction are satisfactory. In female patients, antefixation of the uterus should be performed before or together with an introitusplasty to prevent uterine prolapse. In male patients, however, surgery is performed at the expense of fertility. Detailed discussions with the patients and their patients should include not only the question of primary bladder closure versus urinary diversion, but also the pros and cons of correction of the external and-in females-the internal genitalia.

Adult↗

Detection of a germline mutation and somatic homozygous loss of the von Hippel-Lindau tumor-suppressor gene in a family with a de novo mutation. A combined genetic study, including cytogenetics, PCR/SSCP, FISH, and CGH.

von Hippel-Lindau (VHL) disease is a pleiotropic disorder featuring a variety of malignant and benign tumors of the eye, central nervous system, kidney, and adrenal gland. Recently the VHL gene has been identified in the chromosomal region 3p25-26. Prognosis and successful management of VHL patients and their descendants depend on unambiguous diagnosis. Due to recurrent hemangioblastomas, a29-year-old patient without familial history of VHL disease was diagnosed to be at risk for the disease. Histopathological examination of a small renal mass identified a clear cell tumor with a G1 grading. Genetic characterization of the germline and of the renal tumor was performed. Polymerase chain reaction/single strand conformation polymorphism (PCR/SSCP) analysis with primers from the VHL gene identified a deletion of a single nucleotide in exon 2 in the patient's germline and in the tumor, but not in the DNA of his parents. This deletion therefore must be a de novo mutation. Comparative genome hybridization (CGH) and fluorescence in situ hybridization (FISH) analysis of the G1 tumor with differentially labelled yeast artifical chromosome (YAC) clones showed loss of 3p and of the 3p26 signals, respectively. In conclusion, we identified a de novo germline mutation in the VHL gene of a young patient and a somatic chromosome 3p loss at the homologous chromosome 3 in his renal tumor. Our results suggest a recessive mode of inactivation of the VHL gene, providing solid evidence for its tumor-suppressor gene characteristics. Our data show the diagnostic potential of genetic testing, especially in patients without VHL family history. Furthermore, the findings of homozygous inactivation of the VHL gene in a G1 tumor support the notion that the inactivation of the VHL gene is an early event in tumorigenesis of renal cell carcinoma.

Adult↗

Colonic conduit in children: protection of the upper urinary tract 16 years later?

PURPOSE: Complication rates of up to 86.6% have been reported after creation of an ileal conduit. In contrast to others, we construct an antirefluxing isoperistaltic colonic for incontinent diversion in children. MATERIALS AND METHODS: Between 1968 and 1989 a colonic conduit was created in 105 patients up to age 20 years for neurogenic bladder (76), bladder exstrophy (16) and other reasons (13). Long-term followup (minimum 5 years, mean 16.3 years, range 5 to 26) was possible in 84 patients (159 renal units). RESULTS: Early and late stenosis at the ureterocolic anastomosis, and stomal stenosis occurred in 7.6 and 15.5% of the cases, respectively. Renal calculi developed in 8.2% of the renal units. Eight kidneys without function after recurrent pyelonephritis, calculi or stenosis at the ureterocolic anastomosis were removed during followup. Compared to preoperative status 3 of the remaining 151 renal units had increased dilatation of the upper urinary tract at the last followup. A total of 31 patients had complications during followup and 18 underwent conversion to continent urinary diversion. CONCLUSIONS: When incontinent urinary diversion is necessary in children, a colonic conduit with the option of continent conversion should be created before deterioration of the upper urinary tract.

Adolescent↗

Intraoperative evaluation of renal cell carcinoma: a prospective study of the role of ultrasonography and histopathological frozen sections.

PURPOSE: Nephron sparing surgery is being performed increasingly for treatment of renal cell carcinoma, including in select patients with a normal contralateral kidney. The number of tumors in the involved kidney (single versus multiple) and presence or absence of perinephric fat involvement (pathological stage T1 to 2 versus T3A) are important prognostic factors. In a prospective study we evaluated the accuracy of intraoperative histopathological frozen section analysis of renal capsular biopsies for assessing local tumor stage, and the accuracy of intraoperative ultrasonography for assessing tumor focality. MATERIALS AND METHODS: Intraoperative frozen section biopsies and ultrasonography were compared with information obtained from preoperative computerized tomography (CT), intraoperative inspection of the kidney by the surgeon and permanent histopathological specimens. RESULTS: We evaluated 99 patients (102 kidneys) with localized sold renal masses undergoing either radical nephrectomy (48) or nephron sparing surgery (54). Final pathological analysis revealed 95 renal cell carcinomas (stage T3A in 24), 6 oncocytomas and 1 angiomyolipoma. Multiple tumors were detected in 18 of 102 kidneys overall. Frozen section analysis identified 87% of the stage T3A lesions with no false-positive results, compared to CT, which only identified 67%. Ultrasonography identified 14 of 18 multifocal tumors (78%) and was not more accurate than the combination of CT and intraoperative inspection. However, during nephron sparing surgery ultrasonography was useful to localize the intrarenal extent of tumors (17 cases). CONCLUSIONS: Our results clarify the role of intraoperative ultrasonography and frozen section analysis in patients undergoing nephron sparing surgery for renal cell carcinoma. Frozen section analysis may be useful in select patients with small peripheral tumors who are under consideration for elective nephron sparing surgery.

Carcinoma, Renal Cell↗

Radical cystectomy with or without adjuvant polychemotherapy for non-organ-confined transitional cell carcinoma of the urinary bladder: prognostic impact of lymph node involvement.

OBJECTIVES: To analyze the effectiveness of adjuvant polychemotherapy after radical cystectomy for non-organ-confined transitional cell bladder cancer (Stages pT3b, pT4a, and/or pN1 or pN2). METHODS: Of 166 consecutive patients undergoing cystectomy at two institutions from 1987 to 1993, 80 received adjuvant polychemotherapy with methotrexate, vinblastine, and cisplatin plus doxorubicin (MVAC) or epirubicin (MVEC), whereas 86 had cystectomy only. The patients were evaluated for relapse-free survival and length of progression-free interval on the basis of follow-up data obtained in 1995 and 1996. RESULTS: Kaplan-Meier analysis revealed a significantly higher progression-free rate for patients after adjuvant chemotherapy (P = 0.0002, log-rank test). With and without adjuvant chemotherapy, prognosis declined in a stepwise manner, depending on the extent of lymph node involvement. Nevertheless, the superior prognosis of the chemotherapy group could be demonstrated at each lymph node stage. Of the 166 patients, 49 had initially entered a prospective trial comparing adjuvant with no adjuvant treatment. That study was discontinued in December 1990 after an interim analysis revealed a significant prognostic advantage in favor of the 26 patients randomized to receive chemotherapy compared with the 23 control patients. Current follow-up data continue to demonstrate a significant improvement in progression-free survival in favor of patients randomized to receive adjuvant chemotherapy (P = 0.0040). The follow-up period of patients living free of disease ranges from 58 to 96 months. CONCLUSIONS: Adjuvant chemotherapy with MVAC/MVEC leads to significant prolongation of relapse-free survival and improvement of the definitive cure rate after radical cystectomy for locally advanced transitional cell carcinoma of the urinary bladder.

Adult↗

Transurethral prostatectomy: a long-term follow-up study of 166 patients over 80 years of age.

OBJECTIVES AND METHODS: In a retrospective analysis, the medical records of 166 patients over 80 years of age (80-99 years, mean age 82 years) who underwent transurethral prostatectomy (TURP) for clinically benign prostatic hyperplasia (BPH) were reviewed in order to evaluate the morbidity and mortality rates in this special group of patients. The mean follow-up was 60 months (6-85 months). RESULTS: According to the American Society of Anesthesiologists operative risk classification, 147 (88.5%) patients were found to be of groups ASA III and IV. All patients had at least one serious associated medical disease. Early complications occurred in 25.9% (n = 43) of patients. Late significant urology complications were noted in 13.2% (n = 22) of patients. Reoperation was carried out in 4.2% (n = 7) of cases. Two patients died within 30 days after the operation (1.2%). During the period of follow-up 43 patients died. Comparing the survival curve (according to the Kaplan-Meier analysis) of our group with the expected survival rate of the age-matched overall population, no statistical difference could be observed. CONCLUSION: Being aware of the limits of a retrospective study, we believe that TURP as a treatment for BPH in patients over the age of 80 years has a satisfactory outcome with an acceptable morbidity and mortality rate.

Aged↗

The influence of cytokines on the adhesion of renal cancer cells to endothelium.

PURPOSE: The development of tumor metastasis requires direct adhesive interactions between tumor cells and vascular endothelium. We examined the adherence of renal cell carcinoma (RCC) lines to endothelium after stimulation with different cytokines that induce expression of the vascular adhesion molecules endothelial leukocyte adhesion molecule (ELAM)-1, vascular cell adhesion molecule (VCAM)-1 and intercellular adhesion molecule (ICAM)-1, MATERIALS AND METHODS: Human umbilical vein endothelial cells (HUVEC) were used to determine the adhesion of the RCC lines CCF-RC1, 2 and 7 to endothelium. Expression of cell adhesion molecules (CAM) on HUVEC and RCC lines was measured with immunoflowcytometry. RESULTS: Stimulation of HUVEC with rIl-1 beta, rTNF-alpha, or PMA resulted in a time-dependent 1.4- to 2.9-fold increase of RCC adhesion to HUVEC. Significant increased tumor cell binding was observed after 4 hours and paralleled the time-dependent induction of ELAM-1 and VCAM-1. Immunocytometry demonstrated the presence of the ligands sialyl Lewis X and VLA-4 on RCC, and blocking studies with monoclonal antibodies directed against tumor cell-endothelial interactions mediated by VCAM-1/VLA-4 and ELAM-1/sialyl Lewis X demonstrated marked inhibition of tumor cell adherence to cytokine-stimulated HUVEC. CONCLUSIONS: This study demonstrates that cytokine-induced increases in RCC adherence to HUVEC are mediated in part by VCAM-1/VLA-4 and ELAM-1/sialyl Lewis X interactions and suggest that these molecules may play an important role in the ability of RCC to metastasize.

Carcinoma, Renal Cell↗

Current controversies in nephron-sparing surgery for renal-cell carcinoma.

The role of nephron-sparing surgery for renal cell carcinoma is well established in patients with an anatomical or functional solitary kidney (imperative indication) in which a radical nephrectomy would render the patient anephric with subsequent need for hemodialysis. This also encompasses patients with a unilateral renal cell carcinoma and a functioning contralateral kidney when the opposite renal unit is affected by a disease that might threaten its future function, such as renal artery stenosis, chronic pyelonephritis, stone disease or systemic conditions such as diabetes. A functioning renal remant of at least 20% of normal renal parenchyma seems to be necessary to avoid end-stage renal failure in these patients [16]. There have been several reports in the literature of excellent 5-year cancer-specific survival rates of over 80% in such circumstances [12, 15]. These results were confirmed in our institution, with a 5-year cancer-specific survival rate of 83% in over 70 patients with an imperative indication for nephron-sparing surgery. Thereby the prognosis was significantly influenced by the local tumor stage and the grade of malignancy. These data support the efficacy of nephron-sparing surgery in this clinical situation.

Carcinoma, Renal Cell↗

Adjuvant polychemotherapy of nonorgan-confined bladder cancer after radical cystectomy revisited: long-term results of a controlled prospective study and further clinical experience.

A total of 83 patients with nonorgan-confined bladder cancer with or without lymph node metastases (tumor stages pT3b, pT4a and/or pN1, pN2) was evaluated in November 1993 for relapse-free and overall survival. All patients underwent radical cystectomy between 1987 and 1991, 38 underwent adjuvant polychemotherapy with methotrexate, vinblastine and cisplatin plus doxorubicin (M-VAC) or epirubicin (M-VEC). Of the 83 patients 49 had entered a prospective randomized trial comparing adjuvant to no adjuvant treatment. The protocol was activated in May 1987. Patient recruitment was concluded in December 1990 because an interim analysis of the 49 randomized patients revealed a significant prognostic advantage in favor of the 26 patients randomized to the chemotherapy group compared to 23 in the control group (p = 0.0015, log-rank test for relapse-free survival curves). Preliminary data were published in 1992. Of the 26 patients randomized for adjuvant chemotherapy 18 were treated with M-VAC or M-VEC, 7 refused chemotherapy before or during cycle 1 and 1 received chemotherapy without cisplatin because of impaired renal function. The update of patient followup obtained in November 1993 continues to demonstrate a significant improvement in progression-free survival in favor of patients randomized for adjuvant chemotherapy (p = 0.0005). Followup of patients living free of disease ranged from 38 to 78 months. In a second analysis of actual treatment, the total collective of 83 patients treated from 1987 to 1991 was reviewed: 38 who had actually undergone adjuvant M-VAC/M-VEC (18 during the prospective trial and 20 in 1991 as the routinely recommended therapy) were compared with 45 without adjuvant M-VAC/M-VEC (7 refused to participate in the adjuvant trial, 8 randomized for but did not undergo adjuvant M-VAC/M-VEC, 23 belonged to the control group of the trial, and 7 underwent cystectomy in 1991 and remained without adjuvant treatment). This analysis again revealed a significant prognostic advantage in favor of the patients treated with adjuvant M-VAC/M-VEC. We conclude that adjuvant chemotherapy with M-VAC/M-VEC leads to a significant prolongation of relapse-free survival and to an improvement of the definitive cure rates after radical cystectomy for locally advanced transitional cell carcinoma of the bladder.

Adult↗