Symptom scores, watchful waiting and prostate specific antigen levels in benign prostatic hyperplasia.
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Humans↗
Biomedical subjects
U Jonas
Publications and source records attributed to U Jonas.
Electrical and chemical control of smooth muscle activity of rabbit corpus cavernosum in vitro.
OBJECTIVES: This study sought to further elucidate the regulation of cavernous smooth muscle tone and to characterize mechanisms of cavernous activation and relaxation. METHODS: In isolated strips of rabbit corpus cavernosum, extracellular electrical and mechanical activity were recorded simultaneously before and after pharmacologic stimulation. RESULTS: Spontaneous mechanical activity was characterized by fast phasic contractions (frequency 6 to 30 min-1) associated with fluctuations of the extracellular electrical signals. Phasic activity was increased by blockade of potassium channels or by moderate activation of L-type calcium channels. Faster spikelike fluctuations occurred in the electrical activity, indicating the existence of spike discharges. All mechanical and electrical fluctuations were completely abolished by blockade of L-type calcium channels with nifedipine. CONCLUSIONS: Our results indicate that cavernous smooth muscle tone is regulated by both phasic and tonic activation mechanisms caused by the opening of L-type calcium channels and calcium influx through chemically controlled calcium influx/release.
Animals↗
Cytokines and tumor vaccination.
Patients with locally advanced stages of renal cell carcinoma are at high risk of relapse or progress even after initial radical surgery. Based on the proven efficacy of adoptive and active immunotherapeutic approaches of metastatic renal cell carcinoma, a phase II trial was started in 1989 using autologous, Newcastle disease virus modified and lethally irradiated tumor cell vaccines in combination with low-dose recombinant interleukin-2 (1.8 million U) and recombinant interferon-alpha 2a (1.0 million U) for a surgical adjuvant treatment. Patients were vaccinated (subcutaneous injection) once a week for 8-10 weeks and the treatment was started about 4-10 weeks after surgery. Up to now more than 208 patients with locally advanced renal cell carcinoma (stages pT2-3a, N1-2, M0; pT3b-4, N0-2, M0) were vaccinated after initial radical surgery (tumor nephrectomy with lymph node dissection and ipsilateral adrenalectomy and if necessary in combination with en bloc removal of venous extensions). We overview a follow-up of 203 evaluable patients with a median disease-free survival of 21 months (range of 2-64 months). During this observation period 18 relapses (8.9%) were diagnosed with 3 local relapses (1.5%), 10 lymph node metastases (5%) and/or distant organ metastases in 9 cases (4.5%). These progressive patients' disease was treated by surgery and/or combined immunochemotherapy. Toxicity encountered on this tumor cell vaccination was mild (WHO grade 1) and was characterized by flu-like symptoms and fever up to 38.8 degree Celsius for some hours beginning at 4 hours after the vaccine/cytokine application. Occasionally a transient local inflammation at the site of injection was observed. The comparison of the risk-factor-adapted group of adjuvant treated renal cell carcinoma patients (locally advanced stages) with historical data gave evidence for an improvement in disease-free survival on vaccination treatment. Although this was not a prospective randomized trial, we can summarize that the surgical adjuvant treatment of autologous tumor vaccines in combination with low-dose cytokines may improve relapse-free and overall survival in patients with locally advanced renal cell cancer.
Adult↗
Successful combination of transrectal electroejaculation and intracytoplasmic sperm injection in the treatment of anejaculation.
We describe the case of a couple whose infertility was caused by the absence of seminal emission following retroperitoneal surgery for testicular cancer. Ejaculate could be retrieved from the husband by rectal probe electroejaculation (RPE) but sperm quality was so poor that conventional in-vitro fertilization was impossible. With intracytoplasmic sperm injection of spermatozoa retrieved by RPE - a combination not reported previously - we were able to induce a pregnancy with successful outcome.
Adult↗
Tamsulosin, the first prostate-selective alpha 1A-adrenoceptor antagonist. Analysis of a multinational, multicentre, open-label study assessing the long-term efficacy and safety in patients with benign prostatic obstruction (symptomatic BPH). European Tamsulosin Study Group.
OBJECTIVE: This open-label extension study evaluated the efficacy and safety of tamsulosin (0.4 mg as a modified release formulation) once daily in patients with benign prostatic enlargement, lower urinary tract symptoms and benign prostatic obstruction (symptomatic BPH) for up to 60 weeks. METHODS: Patients were enrolled from two European, 12-week, placebo-controlled trials. This 60-week interim analysis includes the patients (n = 244) randomized to tamsulosin in the two placebo-controlled trials. RESULTS: The significant improvements in the primary efficacy parameters, maximum urinary flow rate (Qmax) and total Boyarsky symptom score, that were observed during the placebo-controlled trials, were sustained throughout the long-term extension study. Mean Qmax improved from baseline (before initiation of tamsulosin) to endpoint by 13.7% (p < 0.001) and remained between 11.5 and 12 ml/s during the entire follow-up period. Total Boyarsky symptom score improved by 36.2% from baseline to endpoint (p < 0.001). Similarly, the percentage of treatment responders, defined as an increase in Qmax of > or = 30% or a decrease in total symptom score of > or = 25%, remained constant throughout the 60-week period. At endpoint, 69% of patients demonstrated this clinically significant total Boyarsky symptom score response. During the 60-week study period, 51 patients (21%) experienced an adverse event considered to be possibly or probably related to study medication, the most common of which were dizziness and abnormal ejaculation, both occurring in 5% of patients. There were no clinically significant changes in blood pressure or pulse rate during the study. CONCLUSION: Long-term tamsulosin therapy is safe, well tolerated and improvements in urinary flow and symptoms are maintained for at least 60 weeks of treatment.
Administration, Oral↗
[Effect of biological prognostic factors on therapy of non-seminomatous stage I testicular tumors--an assessment of the current status].
At present patients in whom a testicular germ cell tumour in clinical stage I is diagnosed have a long-term survival rate of 98%. For non-seminomatous germ cell tumours in this stage three different treatment options are available: primary retroperitoneal lymphadenectomy (PRLA), the wait-and-see strategy, and primary adjuvant systemic chemotherapy. These therapeutic approaches do not obviously differ in the long-term survival rate of the patients. Abdominal CT scans yield false-negative results in 20-30% of patients with occult metastases. The identification of certain histological characteristics within the primary tumour (vascular and/or lymphatic invasion, presence of embryonal carcinoma, absence of yolk sac elements) allows stratification of patients into groups at high and low risk for tumour progression and/or the presence of retroperitoneal lymph node metastases. The determination of biological and genetic characteristics of the primary tumour in addition to classic histological parameters, does not actually seem to reveal any further prognostic information relating to the biological behaviour of the individual tumour. Therefore, with regard to the outcome of prospective and retrospective MRC studies, patients should be stratified according to the Freedman score into groups at high and at low risk of tumour progression and consequently undergo an aggressive (retroperitoneal lymphadenectomy/systemic chemotherapy) or less aggressive (wait-and-see) treatment adjusted to the aggressiveness of the individual tumour. Prospective studies should be performed to find whether biological characteristics of the primary tumour might reveal any additional prognostic information superior to that yielded by histological parameters and possibly allow an even more subtle classification of the patients into high- and low-risk groups.
Biomarkers, Tumor↗
[Functional electromyostimulation of the penile corpus cavernosum (FEMCC)]. Initial results of a new therapeutic option of erectile dysfunction].
Transcutaneous application of low-frequency electric current in the treatment of partially or temporarily denervated striated muscles is widely used to prevent or treat muscular atrophy. Due to the high regenerative capacity of smooth muscle cells, this approach should be beneficial in the treatment of diseases with smooth muscle degeneration due to partial denervation. Our study was done to evaluate the possible beneficial effect of transcutaneous application of low-frequency electric current to the corpus cavernosum penis in the treatment of erectile dysfunction. After a comprehensive work-up, 22 patients with chronic erectile dysfunction (21/22 vasoactive nonresponders) received daily (3-5 x 20 min) transcutaneous functional electromyostimulation of the corpus cavernosum smooth muscles (FEMCC; zero line symmetric impulses of trapezoid shape, two-channel device with alternating stimulations, f = 10-20 Hz for channel I and 20-35 Hz for channel II; t(i) = 100-2000 microseconds, approx. 12 mA, rise time 0.5 s, stimulation time 5 s per channel, interval between stimulations 0.5 s). Five of 22 patients (23%) regained full spontaneous erections and another three (14%) responded to vasoactive drugs after FEMCC. Fourteen were FEMCC failures, including two who subjectively 'improved'. In a similar group of patients evaluated during the same period but receiving no therapy, no spontaneous improvement of the erectile function was observed. Our preliminary results suggest that FEMCC is feasible and results in an improvement of the erectile capacity in a significant proportion (37%) of patients. Further studies will be carried out to corroborate our results, to improve stimulation parameters and to evaluate selection criteria for FEMCC.
Adult↗
Use of assisted reproductive techniques for treatment of ejaculatory disorders.
Ejaculatory disorders can interfere with the fertility of young adults who suffer from spinal cord injury, have type I diabetes mellitus or have undergone retroperitoneal or intrapelvic operations. Following an overview of causes and treatment of ejaculatory disorders, the data of our centre are presented. From a group of 37 patients with genuine loss of seminal emission, 15 men and their wives were offered a combined treatment of rectal probe electro-ejaculation and artificial reproductive techniques. No serious complications occurred. During 40 cycles with intracorporeal insemination and 11 cycles with extracorporeal fertilization techniques, seven pregnancies were achieved, representing a pregnancy rate of 46% per couple and 14% per cycle for all cycles. Five healthy children were born, all following extracorporeal insemination. The 'take-home baby rate' for this population and for this technique is 45%. In vitro fertilization (IVF) led to one birth, intracytoplasmic sperm injection (ICSI) achieved four live births out of three pregnancies, one being a twin gestation. Since our successes are due to the use of extracorporeal insemination techniques, these are now incorporated in a new, more rational treatment protocol.
Ejaculation↗
Detection of p53 gene alteration in renal-cell cancer by micropreparation techniques of tumor specimens.
Alterations in the p53 tumor-suppressor gene have been identified in a variety of human malignancies, including renal-cell cancer. A technique for the isolation of tumor areas from tissue specimens to analyze formalin-fixed and paraffin-embedded tumors and try to avoid a disturbance of the results due to genetic background signal by the presence of tumor-infiltrating lymphocytes, was established. The presence of lymphocytes within the tumor areas investigated was determined by immunohistochemical staining for CD3, a lymphatic surface antigen. Following the isolation of about 100-200 tumor cells, PCR-directed molecular genetic analysis was performed. A highly informative allelotyping approach for the detection of loss of heterozygosity (LOH), determining BstU1- and VNTR-polymorphisms, a 100-bp marker directly localized in intron 1 of the p53 gene, as well as screening for mutations by single-strand conformation polymorphism analysis (SSCP) in exons 5-8, were used. Out of 44 renal-cancer specimens, 33 (75%) were informative for PCR-directed RFLP-analysis. Allelic loss at the p53 gene locus was observed in 10 of 33 cases (33%). No correlation between p53 gene alteration and T-stage, histological grade or histological differentiation could be observed. Alterations in the p53 gene, as detected by a molecular genetic as well as an immunohistochemical approach, were correlated to overall survival. During univariate analysis histological grade, lymphnode status and the presence of distant metastases could be identified as prognostic parameters for overall survival. During multivariate analysis none of the factors investigated remained an independent prognosticator for survival. Summarizing these results, it seems unlikely that p53 gene alterations will serve as an important new factor for the clinical prognosis of patients with renal-cell cancer.
Adult↗
CHESS classification of bladder-outflow obstruction. A consequence in the discussion of current concepts.
The present discussion on the natural history, growth rate pathophysiology, morbidity, and possible treatment of benign prostatic hyperplasia (BPH) reinforces the need to objectify mechanical BPH-induced obstruction with pressure-flow study. Different methods for the quantification of BPH-induced obstruction exist and the grade of simplification depends on their working mechanism. To review the limitations of the current concepts, 118 BPH patients were selected for computerized pressure-flow data analysis according to quadratic passive urethral resistance relation (PURR) function. The CHESS classification differs from all other concepts due to its two-dimensional character and was developed as a result of the following way of thinking: (1) the whole individual pressure-flow plot is the most accurate basis for further analysis; (2) PURR as the true low-pressure flank of the individual plot is the most favorable definition for mechanical obstruction; (3) PURR quantification requires at least two parameters, footpoint and curvature/slope, with regard to the documented missing significant correlation of both; and (4) a two-parameter-based classification is two-dimensional (CHESS classification).
Aged↗
Functional electromyostimulation of the corpus cavernosum penis--preliminary results of a novel therapeutic option for erectile dysfunction.
Transcutaneous application of low-frequency electric current in the treatment of partially or temporarily denervated striated muscles is widely used to prevent or treat muscular atrophy. Due to the high regenerative capacity of smooth-muscle cells, this approach should be beneficial in the treatment of diseases with smooth-muscle degeneration due to partial denervation. Our study was done to evaluate the possible beneficial effect of transcutaneously applied low-frequency electric current on the corpus cavernosum penis in the treatment of erectile dysfunction. After a comprehensive workup, 21 patients with chronic erectile dysfunction (20/21 vasoactive nonresponders) received daily (3-5 x 20 min) transcutaneous functional electromyostimulation of the corpus cavernosum smooth muscles [FEMCC; zero-line symmetric impulses of trapezoid shape, 2-channel device with alternating stimulations; frequency (f), 10-20 Hz for channel I and 20-35 Hz for channel II; impulse duration (ti), 100-150 microseconds; approx. 12 mA; rise time, 0.5 s; stimulation time, 5 s/channel; pause between stimulations, 0.5 s. In all, 4/21 patients (19%) regained full spontaneous erections and another 3/21 (14%) responded to vasoactive drugs after FEMCC. Overall, 14/21 were FEMCC failures, including 2 who subjectively "improved." In a similar group of patients who were evaluated during the same period but received no therapy, no spontaneous improvement in erectile function was observed.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Localized renal-cell carcinoma: detection of abnormal cells in peritumoral tissue. A cytophotometry and immunocytochemistry study.
To spare organ function, partial resection of early diagnosed renal-cell carcinoma (RCC) is applied for well-localized and small-volume RCC with increasing frequency, although recurrence of the tumor in the same kidney is occasionally observed. The aim of the present study was to establish objective prognostic parameters that would allow the selection of tumors suitable for an organsaving procedure. Of the 160 patients undergoing a radical nephrectomy, 67 were included in this study. In 7/45 patients with lymph-node dissection (15.6%), clinical staging revealed a false-negative lymph-node status. By means of conventional histopathology, multifocality could be demonstrated in 2/67 patients (3%); in 1/67 patients (1.5%), the ipsilateral adrenal gland was unexpectantly tumor-involved. Both tumor tissue and normal peritumoral tissue were examined for the presence of premalignant and tumor cells on the basis of DNA ploidy and of the expression of the tumor-associated G250 antigen, which is specifically expressed at the surface of renal cancer cells. In 40/67 (59.1%) peritumoral tissue specimens, cells with an abnormal DNA content could be observed using automated image analysis. In 12/67 cases (18%), cells obtained from peritumoral tissue also showed an aneuploid DNA histogram; 4/67 (6%) had a tumor-correlated DNA ploidy. Additionally, 38/67 (56.9%) of these tissues, histopathologically classified as normal, contained cells expressing the G250 antigen. These observations were independent of the stage or histological grade of the tumor. These data indicate that classic pathological parameters for tumor staging are insufficient for the detection of multifocality, occurring in more than 15% of cases.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Renal-cell carcinoma with intracaval neoplastic extension: stratification and surgical technique.
Surgical removal continues to be the mainstay in the treatment of renal-cell carcinoma with neoplastic venous extension. The steady improvement of surgical and anesthesiological techniques and the introduction of complete circulatory arrest has dramatically improved the morbidity even of patients with extensive thrombi. If ultrasound or computerized tomography (CT) scanning suggests the presence of a venous extension in a patient with renal-cell carcinoma, cavography, magnetic resonance imaging (MRI), transesophageal color-coded ultrasound, and echocardiography may be needed to resolve the questions of cranial extension and vascular wall infiltration. Surgical stratification and, thus, classification of the venous extension depend on the potential need for complete circulatory arrest. Surgical removal is done en bloc for smaller venous extensions and in a two-step procedure (radical nephrectomy followed by thrombectomy) for more extensive thrombi. In patients with infiltration of the suprahepatic inferior vena cava, the hepatic veins or atrium, pending thrombotic embolism, or large masses of suprahepatic thrombotic material, the use of cardiopulmonary bypass and complete circulatory arrest is recommended.
Aged↗
p53 overexpression as a prognostic factor for advanced stage bladder cancer.
Overexpression of the TP53 gene protein detected by immunohistochemistry appears to identify those patients with superficial bladder cancer at risk of the development of muscle invasive or metastatic disease. However, the role of p53 overexpression in patients with advanced or metastatic bladder cancer is not yet well established. In the present study, 44 specimens from 44 patients with advanced stage bladder tumours (T2-T4) undergoing radical cystectomy were investigated for different biological and clinical characteristics as possible prognostic factors: sex, age, depth of tumour infiltration, T-stage, histological grade, lymph node status, application of adjuvant systemic chemotherapy (MVAC), proliferative activity (staining for proliferating cell nuclear antigen (PCNA) by monoclonal antibody (PC10) as well as overexpression of the p53 oncoprotein (monoclonal antibody pAb 1801)). After a median follow-up of 22 months, 16 of the 23 patients (70%) with more than 40% of tumour cells stained positively for p53 (Group B) died from tumour progression compared with 7 of the 21 patients (33%) with less than 40% of tumour cells positive for p53. During univariate analysis, p53 overexpression (P = 0.008), staining for PCNA (> or = 80% of cells positive) (P = 0.01) and tumour stage (P = 0.01) were significant prognostic factors for survival, among which p53 overexpression (P = 0.023) as well as T-stage (P = 0.012) remained independent significant predictors during multivariate analysis. Prospective studies are needed to confirm the independent prognostic potential of p53 overexpression in patients with advanced bladder cancer. The availability of more refined prognostic factors should assist decision making regarding the value of more aggressive treatment options, such as adjuvant or neoadjuvant chemotherapy, for prognostically defined subgroups of patients.
Adult↗
Porcine detrusor cyclic nucleotide phosphodiesterase isoenzymes: characterization and functional effects of various phosphodiesterase inhibitors in vitro.
OBJECTIVES: This study was undertaken to characterize adenosine 3'5'-cyclic monophosphate (cAMP) and guanosine 3'5'-cyclic monophosphate (cGMP) phosphodiesterases (PDEs) in porcine detrusor smooth muscle and to define their possible role in tension regulation. METHODS: PDEs were isolated from porcine detrusor homogenate by Q-Sepharose anion exchange and calmodulin affinity chromatography. The effects of selective inhibitors of cAMP and cGMP PDEs were investigated on isolated PDEs and on carbachol (1 microM) precontracted detrusor strips. RESULTS: Six PDE isoenzymes were isolated by Q-Sepharose anion exchange and calmodulin affinity chromatography: one calmodulin-stimulated PDE (PDE I) which hydrolyzed mainly cGMP, one cGMP-stimulated cAMP PDE (PDE II), two cAMP-specific PDE (PDE IV alpha and IV beta), and two cGMP-specific PDE (PDE V alpha and V beta). PDE I was potently inhibited in a dose-dependent fashion by papaverine, vinpocetine, and zaprinast; the PDE IVs were potently inhibited by papaverine and rolipram; and the PDE Vs were weakly inhibited by papaverine. In organ bath studies, inhibitors of PDE III (milrinone), IV (rolipram), and V (zaprinast) caused only minor relaxations at high concentrations (200 microM), whereas papaverine and vinpocetine caused relaxations of more than 50%. CONCLUSIONS: Our findings support the involvement of cyclic nucleotide metabolism in the regulation of the detrusor smooth muscle tone in the pig and its regulation by PDEs. The weak action of PDE IV and V inhibitors in vitro may be explained by a possible intracellular compartmentalization of such PDEs and the low cyclic nucleotide turnover rate at the conditions used.
3',5'-Cyclic-AMP Phosphodiesterases↗
p53 immunohistochemistry as an independent prognostic factor for superficial transitional cell carcinoma of the bladder.
Although patients with superficial bladder cancer (Ta, T1) have a generally good prognosis, those patients who develop muscle-invasive tumours or metastatic disease at recurrence do poorly clinically. In the current study 69 patients undergoing complete transurethral resection for superficial transitional cell cancer of the bladder were investigated for different clinical and biological characteristics as possible prognostic factors: age, sex, performance of instillation therapy and immunohistochemical determination of mutational inactivation of p53 tumour-suppressor gene (monoclonal antibody PAb 1801) as well as immunohistochemical determination of the proliferation rate by staining for PCNA (proliferating cell nuclear antigen) (monoclonal antibody PC 10). After a median follow-up of 45.8 months, 12 of 14 patients (85.7%) with more than 20% of cells positive for p53 had disease progression with muscle-invasive growth compared with only one of 55 patients (1.8%) negative for p53 (P < 0.01, chi 2 test). During univariate analysis histological grade (G1 vs G2) (P = 0.0373), positivity for PCNA (> 60% of cells) (P = 0.0033) and positivity for p53 (P < 0.001) were significant prognostic factors for disease progression (log-rank test), while during multivariate analysis only positivity for p53 was a significant predictor for relapse of bladder cancer (P = 0.0029) (multivariate Cox regression analysis). The immunohistochemical detection of mutations of the p53 gene has been demonstrated to be a reliable, easily performed and thereby widely available technique for the investigation of fresh-frozen or paraffin-embedded tumour specimens. The results demonstrate the important role of the p53 tumour-suppressor gene protein in the development and for the progression of bladder cancer. If the high prognostic value of p53 mutations in superficial bladder cancer is confirmed in larger prospective trials, more aggressive therapeutic strategies could be discussed for patients with p53 mutations in their tumour specimens.
Aged↗
Bilateral metachronous testicular germ cell tumors occurring in two non-twin brothers. Case report and review of the literature.
We report here the familial occurrence of bilateral testicular germ cell tumors in 2 non-twin brothers, developing after an interval of 16 and 4 years, respectively. To our knowledge, this is the first report on the occurrence of metachronous and bilateral testicular tumors in non-twin brothers.
Adult↗
Phosphodiesterase isoenzymes in human ureteral smooth muscle: identification, characterization, and functional effects of various phosphodiesterase inhibitors in vitro.
Phosphodiesterases (PDE) are key enzymes regulating intracellular cyclic nucleotide metabolism and, thus, contraction and relaxation of the muscle. At present, five different families of isoenzymes of PDE exist that show a distinct species-specific and organ-specific distribution. The aim of the present study was to analyze the PDE isoenzymes present in the human ureter and to evaluate the functional effects of isoenzyme-specific inhibitors in this tissue. Normal ureteral tissue was obtained during radical nephrectomies, homogenized, centrifuged, and the supernatant fraction was separated using DEAE-Sephacel anion-exchange chromatography. PDE assay was then performed and the isoenzymes characterized on the basis of their kinetic characteristics and their sensitivity to allosteric modulators and inhibitors. In vitro, longitudinal ureteral strips as well as ureteral rings were precontracted, and different selective and nonselective PDE inhibitors were added incrementally. Three different PDE isoenzymes were identified: PDE I (Ca/calmodulin-stimulated), PDE II (cyclic guanosine monophosphate-stimulated), and PDE IV (cyclic adenosine monophosphate-specific). All PDE inhibitors relaxed the strips dose-dependently with an EC50 of 30 microM for papaverine, 40 microM for zaprinast, 25 microM for quazinone, and 0.1 microM for rolipram. The existence of three different PDE isoenzymes was shown in this study. The ureter-relaxing effect of the PDE IV inhibitor at low concentrations, combined with its low effect on the systemic circulatory parameters, may open a possibility of using selective PDE IV inhibitors in the treatment of ureteral colics or ureteral stones.
Chromatography, Ion Exchange↗