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U Jonas

Publications and source records attributed to U Jonas.

At least 37 records · Page 2Linked to original sources
PubMed2003

[Is adrenalectomy an indispensable part of nephrectomy? Results of a multivariate statistical analysis].

Since in the absence of clinically overt metastatic disease tumorous lesions within the adrenal gland are found in only 2-10% of cases, the majority of renal cell cancer patients are overtreated by adrenalectomy as an integral part of nephrectomy. The medical records of 847 patients undergoing adrenalectomy in combination with nephrectomy irrespective of the local extent of the primary tumor or the clinical stage at first diagnosis were reviewed to determine the reliability of currently available imaging modalities regarding the prediction of adrenal gland metastases. Several patient and tumor characteristics correlated with the presence of intra-adrenal metastases, and their prognostic value was determined by a multivariate logistic regression model. Metastatic spread into the adrenal gland was observed in 27 of 847 (3%) patients. In only three of eight patients in whom the adrenal was identified as the only metastatic site, preoperative abdominal CT scans were interpreted as false negative. During multivariate statistical analysis, only the presence of distant metastases, vascular invasion within the primary tumor, and multifocal growth of renal cell cancer within the tumor-bearing kidney were identified to independently predict the likelihood for the presence of intra-adrenal metastases. None of the patient or tumor characteristics evaluated reliably predicted the likelihood for the presence of adrenal metastases in patients without evidence of disseminated metastatic spread. As we believe and as the current investigation demonstrates, routine adrenalectomy should not be recommended in cases of preoperatively normal radiological examinations.

Adrenal Gland Neoplasms↗
PubMed2003

Ureteric reconstruction.

Although the ureter is functionally simply a tube to transport urine, ureteric surgery requires detailed anatomical knowledge and advanced surgical skills, because the ureter has a delicate blood supply. Therefore, the urological surgeon must have distinct strategies available to bridge ureteric defects of various sites and lengths. Furthermore, handling during and after surgery should be individualized to the patient's pre- and intraoperative situation. In this review, the indications for reconstruction of a specific ureteric defect, the required techniques and postoperative recommendations are discussed.

Humans↗
PubMed2003

[Impact of tumor size on long-term survival of patients with organ-confined renal cell cancer].

PURPOSE: As a result of the observation that the potential biological aggressiveness of even early stage renal cell cancer (RCC) strongly correlates with tumor size, the 5th edition of the TNM system (1997), which classifies all renal tumors up to a maximum diameter of 7 cm as T1, was modified in the current classification to distinguish T1a and T1b tumors based on a cut-off of 4 cm. Only a few larger investigations supporting this cut-off are available in the literature and these are based on univariate statistical analysis. To determine whether this cut-off best reflects the correlation between aggressive potential and tumor size and thus differentiates patients at low or high risk of progression, this investigation was performed using both univariate and multivariate statistical analysis. MATERIALS AND METHODS: Between 1981 and 2000, a total of 652 patients underwent tumor nephrectomy for renal cell carcinoma. Of these, the 243 patients with local RCC not extending beyond the renal capsule were subjected to univariate (log rank test) and multivariate (Cox regression model) statistical analysis. RESULTS: It became evident that, while during univariate analysis the prognostic calue of a cut-off size of 4 cm was confirmed, multivariate analysis identified the highest relative risk of cause-specific death (2.93) in those patients with tumors larger than 5 cm maximum diameter. CONCLUSIONS: The 5 cm cut-off thus appears to best determine the clinical prognosis for patients undergoing tumor nephrectomy for early stage renal call cancer. Taking this into consideration, the present study clearly demonstrates the reed for a multivariate statistical approach when the current modification of the TNM classification system is critically reevaluated.

Adult↗
PubMed2003

In vitro construction of urinary bladder wall using porcine primary cells reseeded on acellularized bladder matrix and small intestinal submucosa.

BACKGROUND: Partial or radical cystectomy requires replacement of the urinary reservoir normally achieved by using small or large bowel segments. Our aim was to establish tissue engineering of an bioartificial bladder wall using primary cultures of porcine urothelial (pUC) and bladder smooth muscle cells (pSMC) to be reseeded on different acellular biological matrices. METHODS: Primary porcine cultures of pUC and pSMC were established from open bladder biopsy material 25 mm2 in size. Acellular matrix was generated either from a) porcine bladder wall segments or b) tubular small intestinal submucosa with the still attached decellularized muscularis layer. Reseeding of these matrices with primary cells was done in a two-dimensional static model and in a three-dimensional rotating bioreactor perfused with cell culture medium for a period of 6 weeks. RESULTS: Prior to reseeding the cultured cells were characterized as pUC and pSMC by immunohistochemical staining with either anti-keratin 7 or anti-alpha actin. For both matrices a reseeded double layer cell system of pUC and pSMC could be identified after incubation in the described systems for 6 weeks. CONCLUSIONS: Our results document successful generation of tissue engineered urinary bladder wall, which can be used in further large animal transplantation experiments.

Animals↗
PubMed2002

Surgical bladder preserving strategies in the treatment of muscle-invasive bladder cancer.

Single modality bladder-sparing therapy for muscle-invasive bladder cancer, including transurethral resection (TUR), partial cystectomy, systemic chemotherapy or radiotherapy, have been demonstrated to result in insufficient local control of the primary tumour, as well as decreased long-term survival in the patients when compared to radical cystectomy. Therefore, multimodality treatment protocols that aim at bladder preservation and involve all of the aforementioned approaches have been established. Arguments for combining systemic chemotherapy with radiation are to sensitise tumour tissue to radiotherapy and to eradicate occult metastases that have already developed in as many as 50% of patients at the time of first diagnosis. It has been shown that the clinical outcome observed with this approach approximates that after radical cystectomy. Additionally, a substantial number of patients survive with an intact bladder. However, bladder-sparing approaches are costly, and require close co-operation between different clinical specialists as well as careful follow-up. The good long-term results that are observed after cystectomy and the creation of an orthotopic neobladder make the substantial advantage of a bladder preservation strategy questionable when the patient's quality of life is addressed. Additionally, bladder-sparing therapy-related side effects might result in an increased morbidity and mortality in those patients who need to undergo surgery due to recurrent or progressive disease. Multimodality bladder-sparing treatment is a therapeutic option that can be offered to the patient at centres that have a dedicated multidisciplinary team at their disposal. However, radical cystectomy remains the standard of care for muscle-invasive bladder cancer.

Humans↗
PubMed2002

[alpha 1-receptor blockade in therapy of benign prostatic hyperplasia syndrome. Correct dosing for optimal effectiveness].

Four alpha 1-adrenoceptor antagonists are currently available for the medical treatment of lower urinary tract symptoms suggestive of benign prostatic obstruction in Germany: alfuzosin, doxazosin, tamsulosin, and terazosin. Indirect comparison based on randomized, placebo-controlled trials as well as several direct comparative studies have shown equal efficacy of all four drugs on urinary flow and symptom relief if suggested dosing regimens are applied. A dosing regimen below this recommendation should be restricted to those patients who have a proven satisfactory response to a lower dose.

Adrenergic alpha-1 Receptor Antagonists↗
PubMed2002

[Phytotherapy of benign prostatic hyperplasia. Current evidence-based evaluation].

Despite its popularity as a medication in various European countries or as a nutritional supplement in the United States, the role of plant extracts for the treatment of LUTS due to BPH remains controversial. Only a few randomized clinical trials that meet standard criteria of evidence-based medicine but with relatively short follow-up times and some meta-analyses mainly regarding Serenoa repens and Pygeum Africanum as well as more recent studies on pumpkin seeds have shown clinical effects and good tolerability. To better judge the therapeutic potential of these plant extracts, additional randomized placebo-controlled clinical trials with sufficient follow-up are needed.

Evidence-Based Medicine↗
PubMed2002

[Drug therapy of benign prostatic hyperplasia syndrome with alpha 1-receptor blockers. Basic principles and clinical results].

This article reviews the structure and function of the sympathetic nervous system controlling the myogenic tone of the bladder outlet. Therefore, the sympathetic nervous system is partially responsible for urinary outflow resistance. The alpha 1-adrenoceptor antagonists alfuzosin, doxazosin, tamsulosin, or terazosin are able to reduce bladder outflow resistance, which leads to significant relief of LUTS (20-65%) and improvement of urinary flow (1-4.3 ml/s) in patients with symptomatic BPH. Alpha 1-blocker treatment works irrespective of the severity of symptoms, degree of subvesical obstruction, or prostate size. A significant reduction of residual urine was observed only occasionally, but at least alfuzosin is able to reduce the incidence of acute urinary retention. This article presents the results of 39 randomized, placebo-controlled trials with 14,924 patients as well as trials with alpha 1-blockers and plant extracts or finasteride. The results of these trials indicate that all alpha 1-blockers are equally effective. However, tolerability of alfuzosin or tamsulosin is superior to doxazosin or terazosin. Furthermore, treatment of hypertension with doxazosin or terazosin is no longer recommended due to the increased frequency of cardiovascular side effects seen in the ALLHAT Study. As alpha 1-blockers can relieve symptoms and improve urinary flow more effectively than plant extracts or finasteride, alpha 1-blockers are the treatment of first choice in patients with symptomatic BPH without or with a minor degree of subvesical obstruction.

Adrenergic alpha-1 Receptor Antagonists↗
PubMed2002

Long-term safety, tolerability and efficacy of extended-release tolterodine in the treatment of overactive bladder.

BACKGROUND: The objective of the present study was to examine the long-term safety, tolerability and efficacy of tolterodine extended-release (ER) in patients who had completed 12 weeks' treatment in a randomised, double-blind study comparing tolterodine ER 4 mg once daily (qd), tolterodine immediate-release (IR) 2mg twice daily and placebo. METHODS: Of the 1377 patients completing the 12-week study, a total of 1077 (78%) chose to continue with 12 months' open-label treatment with tolterodine ER 4 mg once daily, irrespective of their previous treatment. Safety was assessed after 3, 6, 9 and 12 months' treatment in the study. Efficacy was evaluated from micturition diary variables and patients' perception of bladder condition and urgency following 3 and 12 months' treatment. RESULTS: 71% of patients completed the 12-month study. Tolterodine ER was safe and well tolerated. Adverse events of the general (14.5%), autonomic (13.2%), gastrointestinal (11.4%), respiratory (9.8%) and urinary (9.1%) systems were the most frequently reported. Dry mouth was the most common event, occurring in 12.9% of patients, and was generally mild in severity. Other adverse events occurred in less than 5% of patients. There was no increase in the frequency of adverse events with long-term relative to short-term treatment. The efficacy of tolterodine was maintained over the 12-month treatment period; relative to baseline there were reductions in the number of incontinence episodes per week (median change -83%) and micturitions per 24 hours (median change -21%) and an increase in volume voided (median change +25%) after 12 months' treatment. An improvement in patient perception of their bladder condition was found in 75% of patients completing the study, and 51% had an improvement in patient perception of urgency. CONCLUSIONS: Tolterodine ER 4mg qd displayed a favourable safety, tolerability and efficacy profile during 12 months' treatment of patients with overactive bladder.

Adult↗
PubMed2002

Incidence and prevalence of lower urinary tract symptoms suggestive of benign prostatic hyperplasia in primary care--the Triumph project.

OBJECTIVE: Benign prostatic hyperplasia (BPH) is one of the most common conditions associated with ageing in men. BPH often presents as lower urinary tract symptoms (LUTS) due to difficulties in voiding and irritability of the bladder. We conducted a retrospective cohort study within the Integrated Primary Care Information (IPCI) database, a general practitioners database in The Netherlands, to assess the incidence of LUTS suggestive of BPH (LUTS/BPH) in the general population. MATERIALS: Our study population comprised all males, 45 years or older who were registered for at least 6 months prior to start of follow-up. The study period lasted from 1 January 1995 to 31 December 2000. Cases of LUTS/BPH were defined as persons with a diagnosis of BPH, treatment or surgery for BPH, or urinary symptoms suggestive of BPH that could not be explained by other co-morbidity. RESULTS: The study cohort comprised 80,774 males who contributed 141,035 person-years of follow-up. We identified 2181 incident and 5605 prevalent LUTS/BPH cases. The overall incidence rate of LUTS/BPH was 15 per 1000 man-years (95% CI: 14.8-16.1). The incidence increased linearly (r(2) = 0.99) with age from three cases per 1000 man-years at the age of 45-49 years (95% CI: 2.4-3.6) to a maximum of 38 cases per 1000 man-years at the age of 75-79 years (95% CI: 34.1-42.9). After the age of 80 years, the incidence rate remained constant. For a symptom-free man of 46 years, the risk to develop LUTS/BPH over the coming 30 years, if he survives, is 45%. The overall prevalence of LUTS/BPH was 10.3% (95% CI: 10.2-10.5). The prevalence rate was lowest among males 45-49 years of age (2.7%) and increased with age until a maximum at the age of 80 years (24%). CONCLUSIONS: The incidence rate of LUTS/BPH increases linearly with age and reaches its maximum at the age of 79 years.

Age Distribution↗
PubMed2002

The need for routine adrenalectomy during surgical treatment for renal cell cancer: the Hannover experience.

OBJECTIVES: To further clarify the need for routine adrenalectomy during the surgical treatment of renal cell cancer, as in the absence of clinically overt metastatic disease, tumorous lesions within the adrenal gland are found in only 2-10% of patients, with most being over-treated by adrenalectomy. PATIENTS AND METHODS: The medical records of 819 patients undergoing adrenalectomy combined with nephrectomy, irrespective of the local extension of the primary tumour or the clinical stage at first diagnosis, were reviewed to determine the reliability of currently available imaging methods in predicting adrenal gland metastases. Several patient and tumour characteristics were correlated with the presence of intra-adrenal metastases, and their possible independent prognostic value was determined by a multivariate logistic regression model. RESULTS: There was metastatic spread into the adrenal gland in 27 of 819 (3.3%) patients. In only three of eight patients in whom the adrenal was identified as the only metastatic site were preoperative abdominal computed tomography scans interpreted as false-negative. On multivariate statistical analysis only the presence of distant metastases, vascular invasion within the primary tumour and multifocal growth of renal cell cancer within the tumour-bearing kidney were identified as independent predictors of the presence of intra-adrenal metastases. CONCLUSIONS: None of the patient or tumour characteristics evaluated reliably predicted the likelihood of adrenal metastases in patients with no evidence of disseminated metastatic spread. However, previously published data indicate that the frequency of metachronous metastases within the contralateral kidney (1.8-3.8%) is significantly higher than the risk of a preoperatively undetected isolated intra-adrenal metastatic lesion when currently available imaging modalities are applied. Therefore, routine adrenalectomy should not be recommended if the preoperative radiological examinations are normal.

Adrenal Gland Neoplasms↗
PubMed2002

Growth hormone, somatomedins and men's health.

According to current basic science as well as the clinical literature, human growth hormone has become an important topic in the field of anti-aging medicine. It is well known that the administration of human growth hormone compensates for the dwarfism syndrome in growth hormone-deficient children and growth hormone is also established as a substitution therapy for adults with pituitary deficiency. The effects mediated by growth hormone comprise an increase in muscle mass, a decrease in body fat, improved physical condition, oxygen consumption and overall quality of life, an improvement of the ratio of high-density lipoprotein to low-density lipoprotein, as well as an increase in bone density. Due to the insulin antagonistic effect of growth hormone as well as its insulin-like growth factor-1-mediated mitogenic effect, there is reason to doubt the safety of administering growth hormone outside the framework of approved indications. In an ongoing study, we are evaluating whether growth hormone and somatomedins might be of importance in the regulation of male sexual performance, including penile erection.

Adult↗
PubMed2001

Expression of the p53 and Maspin protein in primary prostate cancer: correlation with clinical features.

The serine protease inhibitor Maspin has been reported to inhibit the invasiveness and motility of prostate cancer tumor cells. Additionally, a p53-dependent regulatory pathway of Maspin in prostate cancer cell lines has been indicated. The first aim of our study was to determine the prognostic value of Maspin protein expression for the recurrence-free survival of patients undergoing radical prostatectomy for the treatment of clinically localized prostate cancer. Secondly, Maspin expression was correlated to p53 protein expression in order to gain additional information on a possible and previously suggested regulatory influence of the wild-type p53 protein on the Maspin protein expression. Tumor specimens obtained from 84 patients undergoing radical prostatectomy for localized prostate cancer were investigated for the expression of the Maspin and p53 protein by an immunohistochemic approach. Maspin protein expression was correlated with further patients' and tumor characteristics such as tumor stage, histologic grading, regional lymph node status, p53 protein expression and recurrence-free survival of the patients following radical prostatectomy. After a median follow-up of 64 months (24-197 months), 23 of 40 patients (58%) with a negative or decreased Maspin expression (group 1) developed local recurrence or systemic tumor progression in contrast to 8 of 44 patients (18%) with a retained expression of the Maspin protein (group 2) (p = 0.02; log-rank test). The median recurrence-free survival following radical prostatectomy was 26 months (12-37 months) for group 1 patients and 41 months (5-134 months) for patients from group 2 (p = 0.04). A positive immunohistochemic staining reaction for the p53 protein was significantly correlated with a decreased expression of the Maspin protein (p = 0.015; Spearman correlation coefficient). Additionally, loss of Maspin protein expression was correlated to higher tumor stages (p = 0.002) and an increasing histologic dedifferentiation (p = 0.03). This is the first study to indicate that Maspin protein possibly functions as a clinically relevant inhibitor of tumor progression, preventing the local invasiveness and further systemic progression of prostate cancer. Our investigation delivers first hints for a p53-dependent regulatory pathway of the Maspin protein in human prostate cancer.

Adenocarcinoma↗
PubMed2001

Phosphodiesterase isoenzymes as pharmacological targets in the treatment of male erectile dysfunction.

Based on the increasing knowledge of intracellular signal propagation in cavernous smooth muscle tone regulation, which is of major importance to the understanding of both the physiology of erection and the pathophysiology of erectile dysfunction, selective phosphodiesterase (PDE) inhibitors have recently been introduced in the treatment of erectile dysfunction. The first promising clinical data on the use of the orally active PDE5 inhibitor Sildenafil in the treatment of erectile dysfunction were accompanied by boosting research activities on cavernous intracellular signal transduction and phosphodiesterase characterization with the aid of molecular biology and protein chemistry. The presence of mRNA transcripts specific for 14 different human phosphodiesterase isoenzymes and isoforms in human cavernous tissue was shown by RT-PCR: Three isogenes of PDEI, PDE2A and 10A, which hydrolyse cAMP as well as cGMP, the cAMP-specific PDE3A, four isogenes of PDE4, PDE7A and PDE8A, as well as cGMP-specific PDEs PDE5A and PDE9A. Using anion exchange chromatography, the activities of PDE isoenzymes 2, 3, 4, and 5 were detected in cytosolic supernatants of human cavernous smooth muscle. To date, the efficacy and safety of several next generation PDE5 inhibitors for use in the treatment of male erectile dysfunction are under evaluation in vitro and in vivo. Further research will possibly allow identification of diagnostic tools for erectile dysfunction and of even more selective drugs in its therapy.

Cyclic GMP↗
PubMed2001

Central effects of sildenafil (Viagra) on auditory selective attention and verbal recognition memory in humans: a study with event-related brain potentials.

The purpose of this study was to assess possible central side-effects of sildenafil (Viagra) on attention and memory functions. Sildenafil and placebo were administered in young male subjects in a double-blind balanced cross-over design. Behavioral patterns and event-related brain potentials (ERP) were recorded in a spatial auditory attention and a visual word recognition task. While behavioral patterns did not reveal any overt effects of sildenafil, auditory ERPs were indicative of an enhanced ability to focus attention (amplitude enhancement of Nd-effect) and to select relevant target stimuli in the sildenafil condition (P3 component). In the memory task, CNS-effects of sildenafil were evident in a reduction of a negativity in the 150-250 ms range. No overt effects on behavior were observed. Nevertheless, the data reveal CNS-effects of sildenafil necessitating further studies.

Adult↗
PubMed2001

Immunocytochemical distribution of nitric oxide synthase in the human corpus cavernosum: an electron microscopical study using the tyramide signal amplification technique.

Nitric oxide has proven to be an important mediator in the relaxation of human cavernosal smooth muscle. Nevertheless, there are many inconsistencies in the literature regarding the cellular and subcellular distribution of endothelial nitric oxide synthase in the human penis. The purpose of this study was to reexamine the localization of eNOS and nNOS in the cellular anatomy of the human cavernous body by means of electron microscopical immunocytochemistry in combination with the tyramide signal amplification technique (TSA). Using specific antibodies against eNOS and nNOS, the NAPDH-diaphorase reaction and advanced protocols for fixation and staining procederes, the occurrence of NOS isoenzymes eNOS and nNOS were examined in cavernosal specimens of ten male patients who were subjected to surgery for penile deviation. eNOS immunoreactivity and NADPH-d staining was seen to be significantly present in the endothelial cells covering the cavernous spaces and in the endothelium of helicine arteries. In endothelial cells, the NADPH-d reaction product BSPT-formazan was abundantly detectable attached to membranes of the endoplasmatic reticulum and the mitochondria whereas posititve eNOS immunostaining was seen in the endothelial cells throughout their cytoplasm without any particular relation to organelles. No considerable eNOS immunoreactivity was detectable in the trabecular smooth muscle cells. nNOS staining was found in nerve fibers innervating the cavernous body and cavernosal arteries. Our results counteract the hypothesis of the cavernous smooth muscle as a local source of NO and underline the importance of an intact endothelial function for penile erection and the contribution of eNOS to this process.

Biotin↗
PubMed2001

Plasma levels of cyclic guanosine-3',5'-monophosphate in the cavernous and systemic blood of healthy males during different functional conditions of the penis.

The relaxation of cavernous arterial and trabecular smooth muscle is dependent upon the stimulation of guanylyl cyclase activity by nitric oxide (NO), which is released from nerve terminals and endothelial cells within the cavernous tissue, and the subsequent accumulation of cyclic guanosine-3',5'-monophosphate (cGMP) in the intracellular space. The present study was undertaken to determine whether or not plasma levels of cGMP in the systemic and cavernous blood of healthy male subjects change from penile flaccidity to tumescence, rigidity and detumescence. Fifteen adult healthy males were exposed to visual and tactile erotic stimuli to elicit penile tumescence and rigidity. Whole blood was simultaneously aspirated from the corpus cavernosum and the cubital vein in the respective penile stages, and cGMP was determined in plasma aliquots by means of a radioimmunoassay. Mean systemic and cavernous plasma levels of cGMP in the blood samples obtained from the healthy volunteers ranged from 1.2-1.7 pmol/ ml. cGMP levels in the systemic circulation and in the cavernous blood did not change during developing erection, rigidity and detumescence. No significant differences were found between cGMP plasma levels in the systemic and cavernous blood in the different penile stages. Our results may reflect the fact that the stimulation of NO production in healthy males during sexual arousal and developing penile erection either does not yield substantial quantities of cGMP or that the rate of cGMP-extrusion from cavernous smooth muscle cells into the extracellular space accounts only for a minor fraction of plasma cGMP. Moreover, basal levels of cGMP in the blood flushing the lacunar spaces of the cavernous body in the state of developing erection may conceal any local release of cGMP that may occur within the penile erectile tissue. Thus, we conclude that the quantification of cGMP is of no use in the evaluation of the physiologic mechanisms of penile erection in vivo.

Adult↗