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Biomedical subjects

S Madersbacher

Publications and source records attributed to S Madersbacher.

At least 19 recordsLinked to original sources
PubMed2006

Human chorionic gonadotropin (hCG) in the male reproductive tract.

Normal hypothalamic-pituitary testicular and prostatic functions are essential for maintenance of male fertility, whereby glycoprotein hormones (GPH) as well as androgens are major endocrine and local regulators. We have investigated whether the GPH human chorionic gonadotropin (hCG) and the free alpha and beta subunits thereof are produced in the target organs themselves and potentially act as auto/paracrine modulators of fertility. Immunofluorometric assays (IFMAs) based on our panel of highly selective monoclonal antibodies, immunohistochemistry (IHC), confocal laser scanning microscopy (CLSM) and 1- and 2D gel electrophoreses with subsequent western blotting have been utilized for the detection of hCGalpha, hCGbeta and its metabolite hCGbeta core fragment (cf) in human testis, prostate and seminal plasma. Both organs synthesize hCGalpha and hCGbeta, which are subsequently detectable at high concentrations in seminal plasma of healthy probands (n=17): hCGalpha 2630+/-520 ng/mL (mean+/-S.E.M.), hCGbeta 2+/-0.28 ng/mL, hCGbetacf and hCG 0.19+/-0.039 ng/mL. These parameters significantly exceed physiological values, e.g. ten thousand-fold in the case of hCGalpha, in serum of young men (n=20): hCGalpha 0.142+/-0.054 ng/mL (mean+/-S.E.M.), hCGbeta 0.05 ng/mL and hCG 0.004+/-0.003 ng/mL. Levels of these markers were not correlated with sperm counts. Of all body fluids including those of pregnant women seminal plasma is the richest physiological source for genuine free i.e. non-dissociated GPHalpha (M(r,app) 23k) which may even appear as di- or tetramers. Its concentration is similar to that observed in maternal serum (weeks 10-12 of gestation) and in extra-embryonic coelomic fluid. In contrast to those fluids where ratios of free subunits to hCG are in the range of 1:100 highly inverse ratios in the range of 10.000:1.000:1 were observed for hCGalpha:hCGbeta:hCG in seminal plasma. hCGalpha is not derived from heterodimeric GPH suggesting hCG-independent functions of hCGalpha and hCGbeta in male and female fertility.

Blotting, Western↗
PubMed2006

Vascular risk factors and erectile dysfunction in a cohort of healthy men.

To determine the impact of vascular risk factors in the genesis of erectile dysfunction (ED) in a cohort of healthy men. Participants of a health-screening project were carefully selected as men without known vascular disease. Erectile dysfunction was quantified via the IIEF5-questionnaire. All men underwent a detailed health examination including determination of blood pressure, blood lipid profile and fasting serum glucose. In total 1519 men (42.9+/-7.9 years) were analysed. Age (P < 0.01), elevated levels of total cholesterol (P = 0.04) and low-density lipoproteins (LDL) (P = 0.02) were associated with moderately to severely impaired erectile function (IIEF5: <12). Men with total cholesterol >240 mg/dl had a 2.7 (1.5-4.9)-fold increased risk for moderate to severe ED, the respective figure for LDL >160 mg/dl was 2.6 (1.4-4.9). In this well characterized, healthy population, elevated serum lipids are the most important risk factors for the development of ED.

Adult↗
PubMed2006

[Epidemiology of BPH and medication approaches].

A more profound knowledge on the pathogenesis, the natural history and the risk of progression enablesa more differentiated therapy of elderly men with lower urinary tract symptoms due to benign prostatic hyperplasia (BPH) and benign prostatic enlargement as compared to 15 years ago. Phytotherapy is currently not recommended by any international BPH-guideline, because the definitive clinical proof for their clinical efficacy has not been made. alpha1-blockers and 5alpha-reductase inhibitors (5ARIs) are established world-wide. Alpha1-blockers are the medical therapy of choice for symptomatic patients with a low risk of clinical progression (e.g. prostate volume < 30-40 ml). Recent long-term data indicate that alpha1-blockers have no effect on the long-term risk of acute urinary retention and the risk of surgery. 5ARIs should be reserved for patients with a higher risk of progression (e.g. prostate volume > 30-40 ml). 5ARIs significantly reduce the risk of acute urinary retention and the need for surgery.

Adrenergic alpha-Antagonists↗
PubMed2005

[Phytotherapy for BPS. Which products can still be prescribed?].

For decades, plant extracts have been amongst to the most popular drugs for lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH)/benign prostatic enlargement (BPE). Only a few of the many published studies meet the criteria of the WHO-BPH consensus conference. The few placebo-controlled, long-term (>/=6 months) studies suggest a positive effect of some extracts (saw palmetto, beta-sitosterol, urtica, rye-grass, saw palmetto/urtica combination) on LUTS; an effect on uroflow, post-void residual volume, prostate volume and PSA was not consistently demonstrable. Randomised trials against an active comparator (alpha1-blocker, 5alpha-reductase inhibitors) are difficult to interpret. Due to the lack of prospective studies, several meta-analyses have been published that can not, however, replace prospective studies. None of the BPH-guidelines currently recommend plant extracts, yet universally conclude that this is an interesting approach. Further prospective studies using WHO standards are required to reliably determine the role of such extracts in the management of elderly men with LUTS due to BPH/BPE.

Clinical Trials as Topic↗
PubMed2004

[Tips and tricks for nerve-sparing cystectomy].

The aim of radical cystectomy with subsequent urinary diversion is to combine a safe oncological outcome with a satisfactory lower urinary tract function. Recent findings on the anatomy, physiology and nerve supply of the pelvis have resulted in a modified nerve-sparing cystectomy technique. A number of studies have shown that the oncological outcome is not compromised by such a technique; in particular the rate of local recurrences is not enhanced. Nerve-sparing cystectomy is of importance for the lower urinary tract function, including continence status after orthotopic bladder substitution and erectile function. Prerequisites for a nerve-sparing technique are a profound knowledge on the nerve supply of the pelvic organs and a subtle surgical technique. Recent surgical developments, for example in prostate and seminal vesicle sparing cystectomy techniques, indicate that it will be feasible to restore lower urinary tract and also sexual function after radical cystectomy and orthotopic bladder substitution.

Cystectomy↗
PubMed2003

Association of microsomal epoxide hydrolase polymorphisms and lung cancer risk.

Microsomal epoxide hydrolase (mEH) plays a dual role in the detoxification and activation of tobacco procarcinogens. Two polymorphisms affecting enzyme activity have been described in the exons 3 and 4 of the mEH gene, which result in the substitution of amino acids histidine to tyrosine at residue 113, and arginine to histidine at residue 139, respectively. We performed a hospital-based case-control study consisting of 277 newly diagnosed lung cancer patients and 496 control subjects to investigate a possible association between these two polymorphisms and lung cancer risk. The polymorphisms were determined by polymerase chain reaction/restriction fragment length polymorphism and TaqMan assay using DNA from peripheral white blood cells. Logistic regression was performed to calculate odds ratios (ORs), confidence limits (CL) and to control for possible confounders. The exon 3 polymorphism of the mEH gene was associated with a significantly decreased risk of lung cancer. The adjusted OR, calculated relative to subjects with the Tyr113/Tyr113 wild type, for the His113/His113 genotype was 0.38 (95% CL 0.20-0.75). An analysis according to histological subtypes revealed a statistically significant association for adenocarcinomas; the adjusted OR for the His113/His113 genotype was 0.40 (95% CL 0.17-0.94). In contrast, no relationship between the exon 4 polymorphism and lung cancer risk was found. The adjusted OR, calculated relative to the His139/His139 wild type, was for the Arg139/Arg139 genotype 1.83 (0.76-4.44). Our results support the hypothesis that genetically reduced mEH activity may be protective against lung cancer.

Adenocarcinoma↗
PubMed2003

[Rare seminoma metastasis to the corpus spongiosum and urethra].

Anaplastic seminomas account for 5-10% of all seminomas. Their metastatic pattern is similar to the classic form of seminoma. We report on an oligophrenic patient with seminoma pT1 who developed a metastasis to the corpus spongiosum and penile urethra, which was successfully treated by local external radiotherapy resulting in long-term tumor remission over a 4-year follow-up period.

Adult↗
PubMed2002

Sacral distribution of prostatic lymph nodes visualized on spiral computed tomography with three-dimensional reconstruction.

OBJECTIVE: To evaluate the involvement of sacral lymph nodes in prostatic lymphatic drainage, using contemporary radiological imaging techniques. PATIENTS AND METHODS: The study included six patients (mean age 61.8 years, range 51-75) with suspected prostate cancer. First, an oil-based contrast medium was injected into the prostate under transrectal ultrasonographic and fluoroscopic guidance, after which a standard ultrasound-guided sextant biopsy was taken. Before injecting the contrast medium, and 20 min and 24 h thereafter, the patients underwent spiral computed tomography of the pelvic region with three-dimensional reconstruction. RESULTS: In all patients the prostate drained via the sacral lymphatic region. Compared with the iliac lymphatic drainage system, there were fewer and narrower sacral lymph nodes. Prostatic sacral lymph nodes were located at S2 to S5, with an emphasis on S3-4. Lymph nodes were detected as presacral and in the sacral foramen, suggesting a direct lymphatic connection to the bony pelvis. CONCLUSION: These results suggest that sacral prostatic lymphatics are a potential route of spread of prostate cancer cells.

Aged↗
PubMed2002

Association of DHEA-S and estradiol serum levels to symptoms of aging men.

OBJECTIVES: A number of interactions between age-related changes in serum levels of dehydroepiandrostendione sulfate (DHEA-S) and estradiol and symptoms of aging men have been proposed, yet data regarding this issue are scant. We therefore set up a prospective study to analyze these associations. METHODS: In a prospective, cross-sectional study, men aged 45-85 years were recruited. All men completed a questionnaire containing 38 items covering a number of aspects of the aging male. Questionnaires were compiled by using items from previously published and validated questionnaires. Several socioeconomic parameters were also determined. In parallel, serum levels of testosterone, free testosterone, luteinizing hormone (LH), follicle stimulating hormone (FSH), DHEA-S, estradiol, sex hormone binding globulin and prostate-specific antigen (PSA) were quantified by commercially available immunoassays. RESULTS: A total of 375 men with a mean age of 59.9 +/- 9.2 years (mean +/- standard deviation) were analyzed. Average DHEA-S and estradiol levels of 135.8 +/- 90.9 micrograms/dl and 29.7 +/- 14.6 pg/ml, respectively, were recorded. DHEA-S serum levels were negatively correlated to patient age, sexual function score, total score and PSA. Estradiol serum levels were positively correlated to testosterone and free testosterone. None of the other scores or questions revealed a correlation with DHEA-S or estradiol serum levels. CONCLUSION: This prospective study elucidates only small interactions between partial androgen deficiency of the aging male (PADAM)-related symptoms and serum levels of DHEA-S and estradiol. Nevertheless, the data suggest an impact of DHEA-S on sexual function.

Age Factors↗
PubMed2001

Polymorphisms of glutathione-S-transferase genes (GSTP1, GSTM1 and GSTT1) and prostate-cancer risk.

Several polymorphic glutathione-S-transferase (GST) enzymes are involved in the metabolism of a number of potential prostate carcinogens and are thought to engage in the transport of steroid hormones. A case-control study was conducted to determine the association of the GSTP1, GSTM1 and GSTT1 polymorphisms and prostate-cancer risk. The study population consisted of 166 patients with previously untreated, histologically proven prostate cancer and 166 age-matched control patients with benign prostatic hyperplasia (BPH), all of them Caucasians. In the GSTP1 gene, 2 polymorphic alleles, GSTP1*B and GSTP1*C, have been described in addition to the wild-type allele, GSTP1*A. Both polymorphic GSTP1 alleles have an A-to-G transition in exon 5, causing an isoleucine-to-valine change. The GSTP1*C allele has an additional transition from C to T. For GSTM1 as well as GSTT1, the polymorphic allele is a deletion of the gene. The proportion of individuals homozygous for the GSTP1 variant alleles (GSTP1*B/*B, GSTP1*B/*C and GSTP1*C/*C) was significantly lower in prostate-cancer patients (4.8%) than in BPH controls (14.5%), and the odds ratio (OR) was 0.24 [95% confidence interval (CI) = 0.09-0.61). The heterozygous genotypes (GSTP1*A/*B and GSTP1*A/*C) were also lower in the cancer group, though this was not significant. On the contrary, no significant effect on prostate-cancer risk was detectable for either GSTM1 (OR = 0.86, 95% CI = 0.55-1.36) or GSTT1 (OR = 0.78, 95% CI = 0.43-1.42). Of the polymorphic GSTs, GSTP1 is the most interesting candidate as a biomarker for prostate-cancer risk as we found a 76% reduced risk in men homozygous for the polymorphic GSTP1 alleles compared to those with wild-type GSTP1.

Aged↗
PubMed2001

High-grade prostate cancer is associated with low serum testosterone levels.

BACKGROUND: The aim of this study was to assess whether low serum testosterone levels in men with newly diagnosed prostate cancer have an association to the endocrine status, prostate-specific antigen (PSA) levels, Gleason score, and androgen receptor expression. METHODS: Besides a full clinical work-up, the following hormones were quantified in men with newly diagnosed prostate cancer by serum analysis: total testosterone, human luteinising hormone (hLH), human follicle stimulating hormone (hFSH), estradiol, and dehydroepiandrostendione (DHEA). In a subgroup of men, androgen receptor expression was determined immunohistochemically. RESULTS: One hundred and fifty six patients (65.7 +/- 8.5 yrs) with a mean PSA of 29.8 ng/ml (median: 7.4 ng/ml) were analysed. Fifty-two patients (33%) had a partial androgen deficiency (serum testosterone < 3.0 ng/ml). These men had lower hLH (3.3 vs. 5.9 mIU/ml), hFSH (6.2 vs. 8.4 mIU/ml), and estradiol (18.8 vs. 29.1 pg/ml) serum levels. Mean Gleason score was higher (7.4 vs. 6.2) in men with a low serum testosterone, PSA-levels were lower (25.3 vs. 31.9 ng/ml). Mean testosterone levels decreased from 4.1 +/- 1.7 ng/ml in patients with Gleason scores < or = 5 to 2.8 +/- 2.7 ng/ml with Gleason scores > or = 8. Androgen receptor expression was higher in patients with low serum testosterone. CONCLUSIONS: Patients with high Gleason score prostate cancer have lower testosterone and estradiol serum levels. The fact that gonadotropins were lower in parallel suggests a tumor-mediated suppression of the hypothalamic-pituitary-gonadal hormone axis particularly in men with high Gleason score tumours.

Adult↗
PubMed2001

Lymphatic drainage of prostatic transition and peripheral zones visualized on a three-dimensional workstation.

OBJECTIVES: To determine whether the prostate has lymphatic/lymph node drainage that is not sampled by conventional lymphadenectomy and whether the transition and peripheral zones of the prostate have a different lymphatic drainage, because up to one quarter of lymph-node-negative patients who undergo radical prostatectomy will develop distant metastases. METHODS: Ten patients (mean age 62.3 years, range 50 to 76) scheduled for transrectal ultrasound-guided sextant biopsy because of an elevated serum prostate-specific antigen level of 4 to 10 ng/mL and a normal digital rectal examination were included in this study. All patients underwent ultrasound-guided sextant biopsies. Subsequently, an oily contrast medium was injected into the transition zone (group A, n = 5) or peripheral zone (group B, n = 5) of the prostate under transrectal ultrasound guidance and fluoroscopy. Immediately, 1 hour, and 24 hours after the procedure, anteroposterior and lateral radiographs were obtained. In addition, spiral computed tomography of the abdomen was performed 10 minutes after the procedure and analyzed on a three-dimensional workstation. RESULTS: No difference in the lymphatic drainage system between the transition and peripheral zones of the prostate was found. In all patients (n = 10), the lymphatic drainage comprised three major routes: (1) the prostate to the lymph nodes along the lateral bony wall of the pelvis to the angle of internal/external iliac lymph nodes to the common iliac lymph nodes, (2) the prostate to the perineal floor to the pudenda internal lymph nodes to the angle of the internal/external iliac lymph nodes to the common iliac lymph nodes, and (3) the prostate to the sacral lymph nodes. In all 10 patients, main contrast medium enhancement was seen immediately after procedure indicating drainage from the prostate to the lymph nodes along the lateral bony wall of the pelvis. Presacral lymph node enhancement was seen in all patients only in the late (24 hours after contrast injection) radiograph. CONCLUSIONS: Our data suggest that the main lymphatic drainage, irrespective of the prostatic region (transition or peripheral zone), runs to the pelvic regions that are mostly removed by standard lymphadenectomy techniques. However, one has to bear in mind that the prostate has some lymphatic drainage that is not covered by standard lymphadenectomy and therefore carries the risk of metastatic tumor spread.

Aged↗
PubMed2001

Association of vitamin D receptor and 17 hydroxylase gene polymorphisms with benign prostatic hyperplasia and benign prostatic enlargement.

OBJECTIVES: To determine whether polymorphisms in 17 hydroxylase (CYP17) and vitamin D receptor (VDR) genes have an association to prostate volume/histology and endocrine patterns in elderly men with lower urinary tract symptoms (LUTS). METHODS: Elderly men with LUTS underwent the following investigations: International Prostate Symptom Score (IPSS), uroflowmetry, serum prostate-specific antigen (PSA) assessment of prostate volume, and an endocrine study. Polymorphisms of CYP17 (T-->C substitution in the 5' promoter region) and VDR (T1055C) genes were detected by polymerase chain reaction followed by restriction-length polymorphism analysis, using DNA from peripheral white blood cells. Clinical and endocrine parameters and the prostate stroma/epithelial ratio were correlated to CYP17 and VDR genotypes. RESULTS: A total of 148 (mean +/- SD, 67.0 +/- 9.7 years) patients were analyzed. IPSS (17.8 +/- 7.0), prostate volume (41.9 +/- 17.9 cc), maximum flow rate (10.9 +/- 5.8 mL/s), and PSA (4.7 +/- 4.7 ng/mL) indicate a typical LUTS population. Mean endocrine levels were consistently within age-specific reference values. Neither CYP17 nor VDR gene polymorphisms revealed an association to prostate size, PSA, clinical parameters, and endocrine parameters. Men who had the A1/A1 CYP17 genotype had on average a greater stromal/epithelial ratio than men with the A1/A2 or A2/A2 genotypes, yet after adjusting for multiple testing, this significance disappeared. CONCLUSIONS: Gene polymorphisms of CYP17 and VDR have no association to prostate volume, clinical parameters, and endocrine parameters in elderly men. The association of CYP17 polymorphism and prostate histology warrants further studies. Assessment of gene polymorphisms might provide new insights into the pathogenesis of benign prostatic hyperplasia and benign prostate enlargement and may hold promise as genetic biomarkers of this disease.

Aged↗
PubMed2001

A low-molecular-weight fraction of human seminal plasma activates adenylyl cyclase and induces caspase 3-independent apoptosis in prostatic epithelial cells by decreasing mitochondrial potential and Bcl-2/Bax ratio.

The majority of elderly men are affected by benign and malign diseases of the prostate that are governed by endocrine factors and local stromal/epithelial and luminal/epithelial interactions. Prostate epithelial cells secrete numerous factors into the seminal plasma (SMP) that are thought to be responsible for nutrition, accurate pH, and ionic environment of sperm. Our hypothesis assumes that prostatic factors responsible for optimal fertility might have retrograde influences on epithelial cell growth, differentiation, and function. SMP was analyzed for proteins and other biologically active substances by size exclusion high-performance liquid chromatography. Each fraction was investigated for its effect on cell growth and death. A low molecular mass fraction (2-4 kDa) was responsible for inducing apoptosis in proliferating prostate epithelial cells. Signal transduction was mediated by the production of cAMP; no significant changes in tyrosine phosphorylation of membrane receptors were observed. Mechanisms of apoptosis, i.e., caspase- and mitochondria-dependent pathways, were investigated in prostate epithelial cells by caspase activity assays, annexin/propidium iodide staining, changes in mitochondrial potential, p53, Par-4, Bax, and Bcl-2 protein levels. SMP induced p53- and Bcl-2-dependent apoptosis without activation of caspase-3. Obviously, SMP contains protective factors that help eliminate degenerated cells and control epithelial renewal. Age-related changes in the composition of SMP or the susceptibility of epithelial cells might, therefore, contribute to proliferative prostatic diseases

Adenylyl Cyclases↗
PubMed2001

Prostate cancer in Austria: impact of prostate-specific antigen test on incidence and mortality.

The aim of the study was to assess the impact of prostate-specific antigen (PSA) testing on prostate cancer mortality in Austria. A join-point regression model and permutation tests were used to identify changes in the slope of age-specific trends respectively calculating the annual percentage change (APC). Age-adjusted incidence increased (P < 0.01) between 1983 and 1997 by 79% from 52.2 to 93.6 cases per 100 000 men/year. Incidence in localized/regional stage disease increased in all ages by 143% from 25.7 to 62.4 cases per 100 000 men/year. Incidence in distant disease decreased (P < 0.01) between 1983 and 1997 in all ages by 38% from 9.5 to 5.9 cases per 100 000 men/year. Incidence in unstaged disease increased (P < 0.01) between 1983 and 1997 in all ages by 300% from 4.5 to 18 cases per 100 000 men/year. Age-adjusted mortality increased (P < 0.05) by 13% from 26.8 in 1983 to 30.3 deaths per 100 000 men/year in 1999. No significant changes of trends in mortality rates were detected in the age groups 50-59 years. In the age group 70-79 years the trend changed (P < 0.05) direction in 1991 and in 1994; 1983 through 1991 APC = 3.52 (95% CI 1.37, 5.72), 1991 through 1994 APC = -10.27 (95% CI -26.20, 9.1) and 1994 through 1999 APC = -0.25 (95% CI -4.55, 4.24). PSA testing increased incidence but no impact on mortality in the target population can be observed so far.

Age Distribution↗