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G Bartsch

Publications and source records attributed to G Bartsch.

At least 91 records · Page 5Linked to original sources
PubMed2000

Effects of alpha1-adrenoceptor antagonists on cultured prostatic smooth muscle cells.

BACKGROUND: alpha1-adrenoceptor (alpha1-AR) antagonists, used to relieve the lower tract urinary symptoms (LUTS) in benign prostate hyperplasia (BPH) patients, are thought to act in inhibiting the contraction of stromal smooth muscle. An attempt was made using new technology to visualize and quantify the effect of alpha1-AR antagonists in a cell culture model of prostatic smooth muscle cells (SMC). METHODS: Prostatic smooth muscle cells cultured from human prostate tissue were treated with alpha1-AR agonists and antagonists. The effects on cell growth, cell contraction, differentiation status, and apoptosis were determined by means of an MTT cell viability assay, time-lapse video microscopy, RT-PCR analysis, and FACS analysis of annexin V/propidium iodide-stained cells, respectively. RESULTS: Prostatic smooth muscle cells derived from prostate tissue expressed SMC-specific markers. They showed spontaneous contractions, and phenylephrine increased the percentage of contracting cells by 3-fold. alpha1-AR antagonists inhibited spontaneous as well as phenylephrine-induced contractions. Long-term treatment with doxazosin induced differentiation tended towards a contractile phenotype, as indicated by an increase of the ratio of smooth muscle heavy chain myosin subtypes SM2/SM1. There was, however, no effect on cell growth. High concentrations of antagonist (100 microM) induced apoptosis in about 80% of the treated SMC. This effect was not cell-type-specific and was also seen in skin fibroblasts and immortalized prostate epithelial cells. CONCLUSION: In an easy-to-handle cell culture model of prostatic smooth muscle cells, the effects of alpha1-AR antagonists on cell contraction, growth, and differentiation can be investigated. The results indicate that in addition to inhibition of cell contraction, alpha1-AR antagonists have the potential to induce apoptosis.

Adrenergic alpha-1 Receptor Antagonists↗
PubMed2000

Androgen receptor--an update of mechanisms of action in prostate cancer.

Androgen receptor (AR), a key nuclear transcription factor in the prostate gland, is expressed in all histological types and stages of prostate cancer. The AR regulates proliferation of prostate cancer cells by stimulation of cyclin-dependent kinases. However, in some prostate tumors AR stimulates expression of cell cycle inhibitors, thus leading to down-regulation of cellular proliferation. Androgens, by activation of the AR, control differentiation of prostate cells and synthesis of neutral lipids. There are several mechanisms by which prostate cancer cells adapt to an environment with low androgen supply during endocrine therapy. The AR expression and activity increase in several cell lines that are used as an in vitro model for monitoring changes during long-term androgen ablation. Mutant ARs are of importance for monitoring the natural course of the disease and for determining the response to anti-androgens in metastatic lesions from prostatic carcinoma. In addition, AR activity is up-regulated by various stimulators of intracellular protein kinases. Current research efforts are focused on elucidation of function of AR coregulatory proteins, coactivators and corepressors. Their inappropriate expression and/or function might critically influence cellular events in advanced carcinoma of the prostate. It is hoped that information on these coregulatory proteins will serve as a basis for a more efficient pharmacological inhibition of the AR in advanced carcinoma of the prostate.

Animals↗
PubMed2000

An in vitro model for videoimaging of human bladder smooth muscle cell contractions.

Knowledge regarding human bladder smooth muscle cell (SMC) physiology is very limited. Only a few specific medical therapies for bladder disorders have therefore been established. The objective of this study was to develop a model for videomicroscopy of bladder SMC contractions. Cells were isolated from human cystoprostatectomy specimens and cultured in a modified EMEM medium. These cells were identified as SMCs by means of immunohistochemistry. For videomicroscopy, the culture flasks were coated with a viscous agent to allow cell contraction. Contractions were visualized by means of a cell culture microscope with a time-lapse videosystem. For cholinergic stimulation of the cells, acetylcholine, in concentrations ranging from 100 microM to 10 mM, was applied. The percentage of contracting cells within the observation field was evaluated for quantitative analysis. In control experiments without contractile stimulant 6% of the cells were observed to contract. Stimulation with acetylcholine induced a significant dose-dependent increase to 47% in contracting cells. These results demonstrated that videomicroscopy is an appropriate tool to investigate the contraction mechanisms of bladder SMCs. This model offers the possibility of studying drug effects on the human detrusor in vitro.

Acetylcholine↗
PubMed2000

Anatomic and functional studies of the male and female urethral sphincter.

A total of 28 human specimens (14 male, 14 female) was used to perform macro- and microscopic studies on the morphologic basis of the urethral continence mechanism. Furthermore, functional studies were performed in six sheep, with the aim of looking at the pudendal and autonomic innervation of the urethra and the rhabdosphincter, as well as the changes of autonomic innervation after selective denervation. Transurethral ultrasound was performed in 34 continent patients, in order to visualize the contractions of the rhabdosphincter. The membranous urethra is innervated by branches of the autonomic pelvic plexus. The rhabdosphincter is an omega-shaped loop of striated muscle fibers that is innervated by the pudendal nerves. These results are supported by the results of animal experiments that show that the autonomic nerves predominantly innervate and regulate the upper part of the urethra, whereas stimulation of the pudendal nerves leads to a contraction of the lower part of the sheep urethra. In electron-microscopy, marked degeneration of the smooth muscle cells could be seen in the sheep with bilateral denervation.

Adult↗
PubMed2000

Quality of life after cystectomy and orthotopic neobladder versus ileal conduit urinary diversion.

The impact of bladder removal and urinary diversion for patients' everyday life is largely unknown. The aims of this study were to compare subjective morbidity of ileal neobladder to the urethra versus ileal conduit urinary diversion and to elucidate its influence on quality of life. A total of 102 patients who underwent cystectomy due to a bladder malignancy were included in the study. In 69 patients (67.6%) an orthotopic neobladder and in 33 patients (32.4%) an ileal conduit was performed as urinary diversion. The compliance was 99% and mean follow-up was 37 months. All patients completed two retrospective quality of life questionnaires, namely the QLQ-C30 and a questionnaire developed at our institution to ask for urinary diversion specific items. The questioning and assessment was performed by non-urologists. The results obtained from the validated (QLQ-C30) and our own specially compiled questionnaire clearly demonstrate that patients with an orthotopic neobladder are more able to adapt to the new situation than patients with an ileal conduit. In addition, neobladder to the urethra improves the quality of life because it improves self-confidence, causes better rehabilitation as well as the restoration of leisure, professional, travelling, and social activities, and reduced risk of inadvertent loss of urine. For example, 92.8% of neobladder patients did not feel handicapped at all, and 87% did not feel sick or ill, in contrast to 51.5% and 66.7% of ileal conduit patients, respectively. Of the neobladder patients, 74.6% felt absolutely safe with the urinary diversion in contrast to 33.3% in the ileal conduit group. Only 1.5% of neobladder patients had wet clothes caused by urine leakage during the day, versus 48.5% of ileal conduit patients. Moreover, 97% of our neobladder patients would recommend the same urinary diversion to a friend suffering from the same disease, but only 36% of ileal conduit patients would do so. These results demonstrate that the quality of life is preserved to a higher degree after orthotopic neobladder than after ileal conduit urinary diversion.

Aged↗
PubMed2000

Reconstruction of the lower urinary tract using autologous muscle transfer and cell seeding: current status and future perspectives.

Functioning free-muscle transfer has established itself for the treatment of skeletal muscle deficiency over the last two decades. The capability of skeletal muscle to empty a spherical reservoir has been shown to be lessened if the muscle has contracted due to dissection. Currently there is no established curative treatment for bladder acontractility. Experimental data and preliminary clinical results have shown that innervated free latissimus dorsi muscle (LD) may serve as a substitute for a dysfunctional detrusor. In a clinical protocol, latissimus dorsi detrusor myoplasty (LDDM) was applied in 11 patients (age 9-68 years) with bladder acontractility due to spinal cord injury (seven patients), congenital malformations (two patients), detrusor myopathy (one patient), and idiopathic causes (one patient) who had required catheterization for bladder emptying for a minimum of 2 years. In all, 10 of 11 patients were capable of voiding volitionally, with eight of them no longer requiring catheterization, throughout the follow-up period of 12-46 months. Transplanted LD activity was confirmed by ultrasonography and flow-mode computerized tomography. It can thus be concluded that emptying of the bladder can be induced through the contractility of reinnervated free LD that has been wrapped around the bladder. An innervated free-LD flap does not undergo the severe muscle fibrosis, contracture, and atrophy that occur after transfer of completely or partially denervated pedicled muscle. Apart from the restoration of deficient detrusor function, microneurovascular transfer of a free-LD flap may be combined with tissue engineering to serve as a basis for bladder augmentation and substitution.

Adolescent↗
PubMed2000

Laparoscopic retroperitoneal lymph node dissection.

INTRODUCTION: Retroperitoneal lymph node dissection (RPLND) is the most accurate method for evaluating the presence of retroperitoneal metastases from clinical Stage I nonseminomatous testicular tumors. We have introduced laparoscopy to reduce the morbidity of open RPLND, which is too high for a diagnostic procedure. As the next step, we replaced open surgery with the laparoscopic approach for Stage IIb tumors to remove residual tumor after chemotherapy. TECHNICAL CONSIDERATIONS: One prerequisite for laparoscopic RPLND is free access to the retroperitoneum, which can be achieved by wide dissection of the colon and duodenum. The borders of the dissection are the same as with open surgery, and complete dissection can be achieved. Bipolar coagulation and the harmonic scalpel have proved very helpful in achieving adequate hemostasis, a crucial point. Venous lesions can be sealed with fibrin glue. CONCLUSIONS: Laparoscopic RPLND is superior to open surgery with regard to morbidity and complication rates, and operative times are equal once enough experience has been collected. The diagnostic accuracy is the same for both methods, and tumor control is not compromised by the laparoscopic approach. The only drawback of laparoscopy is the long and steep learning curve.

Humans↗
PubMed2000

Prostate cancer screening in the Tyrol, Austria: experience and results.

This article summarises the experience and results of different prostate carcinoma screening projects using total prostate specific antigen (PSA) and per cent free PSA as the initial test. Of the 21078 volunteers 1618 (8%) had elevated PSA levels. Of these men 778 (48%) underwent biopsies; 197 (25%) biopsies were positive for prostate carcinoma and 135 (17%) underwent radical prostatectomy. 95 were found to be organ-confined. A PSA cut-off of 2.5 ng/ml in men aged 45-49 years and of 3.5 ng/ml in men aged 50-59 years resulted in an 8% increase in the detection rate of organ-confined disease. 284/2272 men (13%) had elevated PSA levels and prostate carcinoma was detected in 62 men (3%). All patients underwent radical prostatectomy and histological examination revealed organ-confined tumour in all but 8 men. 98/340 men (29%) had biopsies positive for carcinoma; 28 of these patients (29%) had carcinoma that originated in the transition zone only. In the retrospective study, receiver operating characteristic curve analysis showed that by using a per cent free PSA of less than 18% as a biopsy criterion, 37% of the negative biopsies could be eliminated although 94% of all carcinomas would still be detected. In the first prospective study, 106/158 men (67%) with elevated PSA levels below 10.0 ng/ml were further evaluated and 37 (35%) prostate carcinomas were detected. By using a per cent free PSA of <22% as a biopsy criterion, 30% of the negative biopsies could be eliminated although 98% of the carcinomas would still be detected. In the second prospective study, 120/465 men (26%) with total PSA levels between 1.25 and 6.49 ng/ml and a per cent free PSA<18% were further evaluated and 27 (23%) were found to have prostate carcinomas. Receiver operating characteristic curve analysis for PSA transition zone (TZ) density showed that by using a PSA transition zone density of >22 ng/ml/cc as a biopsy criterion, 24.4% of negative biopsies could be avoided without missing a single carcinoma. In the prescreening era the incidence of T1a Grade 1 and 2 carcinomas was 3.1% and the incidence of T1a and T1b Grade 3 carcinoma was 2.3% whereas in the years after the establishment of PSA-based screening the incidence was 4.6 and 1.03% respectively. The rate of organ-confined tumours increased from 28.7% in 1993 to 65.7% in 1997. In this evaluation a new approach, to proceed with a prostate biopsy based upon the individual risk of having prostate cancer rather than a single PSA cut-off point was developed. High total PSA levels, PSA density and PSA transition zone density correlated significantly with high Gleason scores, capsular penetration, a high percentage of cancer in the prostatectomy specimen and a high cancer volume. In this evaluation all of the 95 patients with PSA levels below 3.99 ng/ml who underwent radical prostatectomy showed clinically significant, organ-confined prostate cancer with negative surgical margins. The results of this evaluation suggest that older men have larger tumour volumes compared with younger men with the same PSA levels. These data suggest that PSA-based screening with low PSA cut-off values increase the detection rate of clinically significant, organ confined and potentially curable prostate cancer. Per cent free PSA and PSA transition zone density provide an additional diagnostic benefit over total PSA.

Age Distribution↗
PubMed2000

Inhibition of LncaP prostate cancer cells by means of androgen receptor antisense oligonucleotides.

Currently available methods for treatment of human prostatic carcinoma aim to inactivate the androgen receptor (AR) by androgen deprivation or blockade with anti-androgens. Failure of endocrine therapy and tumor progression is characterized by androgen-independent growth despite high levels of AR expression in metastatic disease. We inhibited AR expression in LNCaP prostate tumor cells by using antisense AR oligodeoxynucleotides (ODNs) and explored whether antisense AR treatment would be conceivable as a therapy for advanced prostate cancer. Among the various AR antisense ODNs tested, a 15-base ODN targeting the CAG repeats encoding the poly-glutamine region of the AR (as750/15) was found to be most effective. Treatment of LNCaP cells with as750/15 reduced AR expression to approximately 2% within 24 hours compared with mock-treated controls. AR down-regulation resulted in significant cell growth inhibition, strongly reduced secretion of the androgen-regulated prostate-specific antigen, reduction of epidermal growth factor receptor expression, and an increase in apoptotic cells. Mis-sense and mismatched control ODNs had no or only slight effects. Antisense inhibition was also very efficient in LNCaP-abl cells, a subline established after long-term androgen ablation of LNCaP cells, resulting in inhibition of AR expression and cell proliferation that was similar to that seen for parental LNCaP cells. This study shows that inhibition of AR expression by antisense AR ODNs may be a promising new approach for treatment of advanced human prostate cancer.

Apoptosis↗
PubMed2000

Evidence for the autoregulation of vesical circulation by intravesical potassium chloride and distension in the normal human bladder.

OBJECTIVES: To determine the influence of distension and intravesical KCl on vesical blood flow in the normal human bladder. Subjects and methods Nine normal volunteers underwent comparative cystometry (NaCl vs 0.2 mol/L KCl; filling rate 50 mL/min). Peak systolic blood flow velocity (PSBFV) and end-diastolic blood flow velocity (EDBFV) were measured in several intramural arteries at a filling volume of 50 mL and at maximum cystometric capacity (Cmax). For these measurements a colour Doppler unit fitted with an endorectal probe was used. The resistance index (RI) was defined as (PSBFV-EDBFV)/PSBFV. RESULTS: In the presence of NaCl, the mean PSBFV increased significantly from 9 cm/s at 50 mL to 17 cm/s at Cmax (512 mL). Compared with NaCl, KCl induced a significantly higher mean PSBFV at 50 mL (15 cm/s). With increasing distension the rise in PSBFV with KCl filling (Cmax 478 mL) was nearly parallel to that obtained on NaCl filling (mean 22 cm/s); the RI did not change. CONCLUSIONS: Bladder distension and intravesical KCl significantly increased the PSBFV. The unchanged RI indicated a concomitant increase in perfusion rates. Hence, the composition of urine (high potassium concentrations and hyperosmolarity) and its storage govern the autoregulation (independent of cardiac output) of vesical circulation, probably by reflexive pathways. These findings provide further evidence for prevesical arteriovenous shunts.

Blood Flow Velocity↗
PubMed2000

Diagnostic effect of an improved preembedding method of prostate needle biopsy specimens.

The authors compared the influence of a conventional and an optimized submitting method of prostate core needle biopsy specimens on the frequency of cancer detected and the pathologic characteristics of the adenocarcinoma bearing biopsy specimens. The patients included were part of the prostate-specific antigen (PSA) screening program of Tyrol/Austria. Of the systematic core needle biopsy specimens from 500 unselected men obtained within 1 year from the Urological Department, University of Innsbruck, the core biopsy specimens of 250 cases were submitted conventionally, floating free in formalin-filled containers, whereas the biopsy specimens of the other 250 cases were stretched and orientated between 2 meshes in tissue cassettes at the time of biopsy before formalin fixation. On 136 cases diagnosed as adenocarcinoma the number and the length of cores as well as number of the cores involved by cancer and the tumor size were morphometrically determined. The diagnosis of benign prostatic hyperplasia, isolated high-grade prostatic intraepithelial neoplasia (PIN), atypical foci suspicious for cancer, and carcinoma was made in 66%, 5.6%, 4.8%, and 23.6% after conventional submission and in 61.6%, 6.4%, 1.2%, and 30.8% of the cases after optimized preembedding respectively. In the adenocarcinoma cases the optimizedly preembedded material showed higher mean total core length (126.5 mm versus 93.9 mm; P < .0001), a higher mean total tumor length (14.1 mm versus 8.6 mm; P = .01), and more cores involved by cancer (2.9 versus 2.4; P = .01) compared with the conventionally worked-up biopsy specimens. Optimized preembedding of core needle biopsy specimens in tissue cassettes could be quickly and routinely done by the assistance of the urologists at the time of biopsy. The significant improvement of the histologic yield of optimizedly preembedded prostatic needle biopsy specimens led to a higher frequency of cancer diagnosis, a reduction of cases with atypical foci suspicious for cancer and a significantly lower number of cases with only 1 core biopsy involved by cancer.

Adenocarcinoma↗
PubMed2000

Androgen receptor protein is down-regulated by basic fibroblast growth factor in prostate cancer cells.

Interactions between polypeptide growth factors and the androgen receptor (AR) are important for regulation of cellular events in carcinoma of the prostate. Basic fibroblast growth factor (bFGF), the prototype of heparin-binding growth factors, and the AR are commonly expressed in prostate cancer. bFGF diminished prostate-specific antigen protein in the supernatants of androgen-stimulated human prostate cancer cells LNCaP by 80%. In the present study, we asked whether the bFGF effect on prostate-specific antigen is preceded by action on AR expression. LNCaP cells were treated with bFGF and AR protein expression was determined by immunoblotting and ligand binding assay. bFGF down-regulated AR protein in a dose-dependent manner showing a maximal effect at 50 ng ml(-1) both in the presence or absence of dihydrotestosterone. Down-regulation of AR protein expression occurred already after 8 h of bFGF treatment and a maximal inhibition was observed 24 h after addition of bFGF to culture media. As AR expression can be reduced by an increase in intracellular calcium levels, we investigated whether the bFGF effect on AR protein is mediated by this mechanism. Calcium release from intracellular stores and store-operated calcium influx after treatment with either bFGF or calcium ionophore A 23187 were measured by single cell fluorescence technique. The ionophore A 23187 was able to induce calcium influx and an increase in cytoplasmic calcium concentration in LNCaP cells. In contrast, bFGF was incapable of eliciting a similar effect. In contrast to AR protein, AR mRNA levels were not affected by bFGF as shown by semiquantitative reverse transcription polymerase chain reaction. In summary, these studies show that bFGF is a potent negative regulator of AR protein expression in the human prostate cancer cell line LNCaP.

Calcium↗
PubMed2000

Renal cell carcinoma in a horseshoe kidney--superselective embolization of a vessel in a remaining calix after partial nephrectomy.

A 51-year-old patient underwent partial nephrectomy because of a renal cell carcinoma in a horseshoe kidney. Postoperatively a remaining calix led to persistent urinoma formation. By means of superselective embolization urine extravasation was stopped successfully. This demonstrates that superselective embolization can be an effective tool in the management of complications after open renal surgery.

Angiography↗
PubMed2000

Partial laparoscopic adrenalectomy for aldosterone-producing adenoma: short-and long-term results.

BACKGROUND AND PURPOSE: Laparoscopic surgery for adrenal gland tumors is the gold standard operative approach now. Adrenal-sparing surgery has special indications. We demonstrated the safety and feasibility of performing adrenal-sparing surgery by means of laparoscopy for aldosterone-producing adenoma (Conn's syndrome). PATIENTS AND METHODS: Between 1995 and 1999, seven patients with Conn's syndrome had laparoscopic adrenal-sparing resection of their tumors. These patients were followed up by means of radiology and biochemistry. RESULTS: All seven patients had successful laparoscopic surgery without complications. Most patients were discharged in 2 to 6 days (mean 3 days). At follow-up, the six patients investigated had normal blood pressure. No recurrences have been encountered with a median follow-up of 12 months in these six patients. CONCLUSIONS: Adrenal-sparing resection of tumors causing primary hyperaldosteronism is technically feasible by means of laparoscopy. This procedure has the advantage of keeping a greater reserve of normal adrenal tissue and of rapid postoperative recovery.

Adenoma↗
PubMed2000

Laparoscopic Fenger plasty.

BACKGROUND: At our department, adults presenting with hydronephrosis secondary to short intrinsic stenoses of the ureteropelvic junction (UPJ) or ventrally crossing vessels are treated with laparoscopic nondismembered pyeloplasty. We herein present our long-term results. PATIENTS AND METHODS: From August 1994 to September 1999, 34 female and 31 male patients presenting with 67 obstructed UPJs underwent laparoscopic nondismembered pyeloplasty. The patients' ages ranged from 11 to 77 (mean 35.6) years. Preoperatively, all patients were evaluated with intravenous urography and isotope scans. In addition, color Doppler ultrasonography was performed to identify crossing vessels at the UPJ. Prior to surgery, a stent was placed, which was left indwelling until 6 weeks after surgery. On the right side, the transperitoneal and on the left, the retroperitoneal approach was used. Following dissection of the UPJ, the obstructing vessels were displaced. The stenosis of the UPJ was corrected by either Fenger plasty (63 UPJs) or Y-V plasty (4 UPJs). Postoperative evaluation included color Doppler ultrasonography, intravenous urography, and isotope studies. RESULTS: The mean operative time was 123 minutes. No intraoperative complications were seen. In 79% of the patients, ventrally crossing vessels were found and displaced from the UPJ. Forty-eight patients have been available for follow-up, which currently ranges from 4 to 60 (mean 25) months. In the most recent nine patients, the position of the crossing vessels relative to the UPJ was also assessed postoperatively by means of color Dopper ultrasonography. The mean distance of the vessels from the UPJ was 1.5 cm. There was a single failure, in a 19-year-old woman who presented with infected hydronephrosis. Laparoscopic nondismembered pyeloplasty failed because the stenosis, which was aggravated by the infection, was too long. The success rate thus was 98%. CONCLUSIONS: At our department, laparoscopic nondismembered pyeloplasty is the preferred method for the management of UPJ obstruction, while dismembered pyeloplasty is performed in rare cases only.

Adolescent↗
PubMed2000

Radical prostatectomy: the value of preoperative, individually labeled apical biopsies.

PURPOSE: Involvement of the prostatic apex with adenocarcinoma is a relatively common finding, as is a positive surgical margin at this location. We evaluated whether a positive apical core biopsy provides preoperative information that may be used as a basis for the subsequent surgical approach in individuals. MATERIALS AND METHODS: We evaluated apical prostate cancer in 240 individually labeled, preoperative apical core biopsies and the corresponding prostatectomy specimen in 120 patients who underwent radical prostatectomy for clinically localized prostate cancer. Sensitivity, specificity, and positive and negative predictive values were calculated for the ability of an individual apical core to predict the side of tumor in the surgical specimen using 2 x 2 contingency tables. Moreover, univariate subset analysis was done for positive biopsies to assess the ability of histopathological characteristics, including Gleason score, cancer length, percent of cancer in the core and distance of cancer from the inked rectal core end, to predict a positive surgical margin at the apex. RESULTS: The positive predictive value of a single positive apical core for identifying tumor location correctly in the prostatectomy specimen was 71.1%, while absent cancer in the apical biopsy had a negative predictive value of 75.5%. Sensitivity was 44.5% for a positive biopsy core. In this context the predictive value of an individual positive apical core biopsy was only 28.8% for predicting surgical margin positivity at the apex. CONCLUSIONS: Cancer and its histopathological characteristics in an individual core biopsy failed to predict apical tumor involvement as well as a positive apical margin at subsequent radical prostatectomy.

Adenocarcinoma↗