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Biomedical subjects

G Bartsch

Publications and source records attributed to G Bartsch.

At least 37 records · Page 2Linked to original sources

[Transrectal three dimensional sonography. Techniques and indications].

In 3-D transrectal ultrasound it is possible, for the first time, to investigate the region of interest in three planes simultaneously. Exact examination of the organs of the small pelvis as well as of pathologic changes in the region of the pelvic floor can be performed with this new imaging technique. The bulbourethral glands can be investigated routinely, which enables the diagnosis of cysts of these glands. The prostatic zones, their relations as well as the growth of the transitional zone during the development of benign prostatic hyperplasia can be visualized. Furthermore, 3-D transrectal ultrasound allows investigation of morphology and function of the rhabdosphincter. The contractility of the muscle can be quantified. 3-D ultrasound guided puncture and drainage of prostatic abscesses represents a minimally invasive therapeutic modality. This technique can be used to place needles as well as implants in the lower urinary tract. Generally, 3-D transrectal ultrasound offers new diagnostic and therapeutic possibilities.

Animals↗

An autocrine loop for vascular endothelial growth factor is established in prostate cancer cells generated after prolonged treatment with interleukin 6.

Concentrations of interleukin 6 (IL-6) and its receptor are increased in human prostate cancer. Prostate cancer LNCaP-IL-6+ cells, established after prolonged treatment with IL-6, have been found to acquire a growth advantage. Vascular endothelial growth factor (VEGF) may accelerate the growth of various tumours by stimulation of VEGF receptor 2 (VEGFR-2). To understand better the regulation of proliferation of LNCaP-IL-6+ cells, the expression of VEGF and VEGFR-2 was here investigated in the LNCaP-IL-6+ subline. VEGF was measured in cellular supernatants by enzyme-linked immunoassay. The expression of VEGFR-2 was assessed by Western blot. LNCaP-IL-6+ and control LNCaP-IL-6- cells were treated with a neutralising antibody against VEGFR-2. VEGF concentrations were 20-fold higher in LNCaP-IL-6+ than in LNCaP-IL-6- cells. The stimulatory effect of IL-6 on VEGF production was abolished by an inhibitor of the signalling pathway for phosphoinositol 3 kinase in LNCaP-IL-6+ and LNCaP-IL-6- cells. Exogenous VEGF did not stimulate proliferation in either LNCaP-IL-6+ cells or controls. VEGFR-2 was detected only in LNCaP-IL-6+ cells, in which the neutralising antibody caused a partial inhibition of cell proliferation. It was concluded that a VEGF autocrine loop is established in prostate cancer cells generated after chronic treatment with IL-6. Because of the upregulation of IL-6 in patients with prostate cancer, these findings might be clinically relevant.

Autocrine Communication↗

Tissue perfusion essential for spermatogenesis and outcome of testicular sperm extraction (TESE) for assisted reproduction.

PURPOSE: In order to determine if there are areas of major and minor perfusion in a single testicle and if the quality of sperm is correlated with quantity of perfusion we collected testicle tissue for TESE in accordance to the local testicle tissue perfusion. METHODS: A patient undergoing TESE underwent testicular perfusion mapping using contrast enhanced ultrasound. The exposed tissue was scanned with a Laser Doppler scanner and perfusion rates were determined measuring tissue perfusion units (TPUs). Tissue was biopsied and sperm were selected and prepared for assisted reproduction. RESULTS: The total amount of isolated sperm correlated highly with the intensity of tissue perfusion showing high number of sperm in areas with high TPUs. CONCLUSIONS: This is the first demonstration that sperm quality and quantity is depending on tissue perfusion within the testicle. To further improve infertility treatment we propose that random biopsies could be replaced by perfusion-dependent collection of testicular tissue.

Biopsy↗

Evaluation and management of renal injuries: consensus statement of the renal trauma subcommittee.

OBJECTIVE: To determine the optimal evaluation and management of renal injuries by review of the world's English-language literature on the subject. METHODS: A consensus conference convened by the World Health Organization and the Societé Internationale d'Urologie met to critically review reports of the diagnosis and treatment of renal trauma. The English-language literature about renal trauma was identified using Medline, and additional cited works not detected in the initial search obtained. Evidence-based recommendations for the diagnosis and management of renal trauma were made with reference to a five-point scale. RESULTS: There were many Level 3 and 4 citations, few Level 2, and one Level 1 which supported clinical practice patterns. Findings of nearly 200 reviewed citations are summarized. CONCLUSIONS: Published reports on renal trauma still rely heavily on expert opinion and single-institution retrospective case series. Prospective trials of the most significant issues, when possible, might improve the quality of evidence that dictates the behaviour of practitioners.

Diagnostic Imaging↗

Genes differentially expressed in prostate cancer.

Because of the heterogeneity of prostate cancer knowledge about the genes involved in prostate carcinogenesis is still very limited. Previously, the use of novel high-throughput technologies offered the possibility to investigate broad gene expression profiles and thus helped to improve understanding of the molecular basis of prostate disease. Many candidate genes have been identified so far which have a more or less strong effect on prostate cancer. This vast number of gene expression changes show that it is unlikely that only one gene promotes prostate cancer. Conversely, it seems more likely that a broad network of molecular changes is involved in the complex cascade of events which lead to tumour formation and progression, respectively. A few of these novel molecular targets are currently under clinical evaluation. This paper gives an overview of several interesting candidate genes which may be useful as improved biomarkers for diagnosis or as targets for developing novel treatment methods.

Biomarkers, Tumor↗

Antiandrogens in prostate cancer endocrine therapy.

Prostate cancer is the most frequently diagnosed tumor in industrialized countries. Endocrine therapy, which is based on interference with androgen signaling is only palliative. Drugs used in prostate cancer therapy are luteinizing hormone releasing hormone (LHRH) agonists and antiandrogens. Application of LHRH agonists leads to suppression of the levels of circulating androgens, and antiandrogens block the function of the androgen receptor (AR). The steroidal antiandrogen cyproterone acetate and nonsteroidal compounds hydroxyflutamide and bicalutamide are used most frequently. They prevent acquisition of a transcriptionally active conformation of the AR. It became clear that tumors progress to therapy resistance in the presence of the AR which might be structurally altered. These mutations generate receptors that respond to other steroids and antiandrogens by increased activation. In addition, AR expression increases during endocrine treatment. AR is also activated by nonsteroidal compounds such as growth factors, interleukin-6, and neuropeptides. Therefore, new experimental approaches are needed to antagonize AR expression and function more efficiently. The AR associates with a number of proteins, coactivators and corepressors. There are indications that expression of some of these proteins is altered in prostate cancer, a fact which might be important for improvement of endocrine therapy.

Androgen Antagonists↗

[Clinical consequences of androgen receptor malfunction].

The androgen receptor (AR), the mediator of the effects of the male sex hormones testosterone and dihydrotestosterone, plays a crucial role in development of male sex and in the function of male sexual organs. Pathological alterations of AR structure and function are a major cause of androgen insensitivity in male pseudohermaphroditism and the accompanying deformations of genital organs, or result in spinal and bulbar muscular atrophy (SBMA). In addition, AR alterations that generate a hyperreactive receptor contribute to the development of resistance to hormone ablation therapy in prostate cancer. AR mutations found in patients with male pseudohermaphroditism usually are missens mutations that result in exchange of a single amino acid and cause complete or partial loss of function. The molecular change underlaying spinal and bulbar muscular atrophy is an extension of a poly-CAG repeat in the AR gene. The affected receptor tends to form aggregates, which damage motoneurons. Androgen ablation therapy puts prostate tumor cells under selection pressure that finally results in development of a hyperreactive androgen receptor that is activated under the conditions of therapy.

Amino Acid Substitution↗

[Tissue engineering in urology. Basic principles and application].

Tissue engineering is a rather new field of science. Despite this fact, some experimental investigations have already been applied in clinical studies. Compared to other medical fields, tissue engineering in urology is well established. Tissue-engineered bulking agents and tissue-engineered bladder augments are being investigated in clinical trials. Even though the knowledge gained in recent years is promising, the results of cellular therapies need to be critically judged before being finally applied in patients. Genetic engineering and stem cell research (adult undifferentiated cells) have had major impact on the field of tissue engineering over the past 2 years. By using the technology of genetic engineering, biochemical and functional qualities of tissues may be modified. Adult stem cells may help to substitute lost tissue in an autologous fashion by isolating undifferentiated cells from the body and by differentiating them into a desired cell type. These cells may be used to form native functional tissue to replace a diseased organ or organ part.

Adult↗

[The value of ultrasound (US) in the diagnosis of prostate cancer].

The value of ultrasound (US) in the diagnosis of prostate cancer has increased in importance in the past decade, which is mainly related due to the increasing incidence of prostate cancer, the most common malignancy in men. The value of conventional gray-scale US for prostate cancer detection has been extensively investigated. The introduction of US contrast agents has dramatically changed the role of US for prostate cancer detection. Advances in US techniques were introduced to further increase the role of US contrast agents. Although most of these advances in US techniques, which use the interaction of the contrast agent with the transmitted US waves are very sensitive for the detection of microbubbles, are mostly unexplored, in particular for prostate applications. First reports of contrast-enhanced US investigations of blood flow of the prostate have shown that contrast-enhanced US adds important information to the conventional US technique. We present a critical evaluation of the current status of transrectal US imaging for prostate cancer detection. Furthermore, we give background information on US contrast agents and imaging modalities. Early results of contrast-enhanced US suggest the feasibility of the use of US contrast agents to enhance US imaging of the prostate. The application of US contrast agents for the detection and clinical staging of prostate cancer is promising. However, future clinical trials will be needed to determine the promise of contrast-enhanced US of the prostate evolves into clinical application.

Biopsy↗

Laparoscopic partial adrenalectomy in patients with aldosterone-producing adenomas: indications, technique, and results.

OBJECTIVES: To report the indications, technique, and results in patients with primary hyperaldosteronism due to aldosterone-producing adrenal adenoma treated by laparoscopic partial adrenalectomy. Laparoscopy has become the technique of choice in adrenal surgery, but adrenalectomy is the standard procedure. Only a few studies have reported on partial adrenalectomy, and the indications and technique have not yet been clearly defined. METHODS: From June 1995 to December 2001, 13 patients presented with hyperaldosteronism and a single adrenal adenoma (Conn's syndrome) and were treated with laparoscopic partial adrenalectomy. The mean age was 60 years, and the average tumor size was 2.1 cm in diameter. A transperitoneal approach was used in all patients, tumors were resected with safety margins by endoshears, and hemostasis was achieved by bipolar coagulation and finally by sealing with fibrin glue. RESULTS: All procedures were finished laparoscopically, and no conversion was necessary. No major intraoperative or postoperative complication was observed. The histologic examination showed adenomas with negative surgical margins in all cases. Postoperative computed tomography revealed a normal blood supply for the remaining adrenal tissue. Blood pressure and aldosterone levels were unremarkable at follow-up, and no local recurrence was observed. CONCLUSIONS: Laparoscopic partial adrenalectomy for aldosterone-producing adenomas is a minimally invasive procedure with a low complication rate. It provides the benefit of retaining functional tissue on the side of the affected adrenal gland. Therefore, we recommend laparoscopic partial adrenalectomy for patients with small, potentially benign, tumors of the adrenal gland, even with a healthy contralateral adrenal gland.

Adrenal Gland Neoplasms↗

Free neurovascular transfer of latisstmus dorsi muscle for the treatment of bladder acontractility: II. Clinical results.

PURPOSE: Until now patients with bladder acontractility were destined to lifelong clean intermittent catheterization with all of its inherent risks. Previous experimental studies demonstrated that voluntary voiding can be restored by microneurovascular free transfer of a carefully selected muscle flap. We present the selection criteria, modifications in technique, followup schedule and long-term results in 20 patients treated with transplantation of latissimus dorsi muscle to the bladder. MATERIALS AND METHODS: In 20 patients with bladder acontractility requiring intermittent catheterization for at least 2 years we performed latissimus dorsi detrusor myoplasty. Preoperative evaluation included urodynamic assessment, cystoscopy, upper tract imaging and electromyography of the rectus muscle. The procedure involves transfer of a free neurovascular latissimus dorsi muscle flap to the pelvis where it is anastomosed to the lowest motor branches of the intercostal nerve and deep inferior epigastric vessels. Patients were instructed to attempt voluntary voiding 3 months postoperatively. Followup included urodynamic evaluation, biannual Doppler ultrasonography and annual dynamic computerized tomography. RESULTS: Annual dynamic computerized tomography and/or biannual Doppler ultrasonography demonstrated vascularization and contractility of all transplanted muscle flaps. Mean followup is 44 months (range 18 to 74). Of the 20 patients 14 were able to void spontaneously within 4 months postoperatively with post-void residual volumes of less than 100 cc, voluntary voiding was restored by bladder neck incision in 4 and 2 (10%) still require self-catheterization. Postoperative detrusor pressures ranged from 5 to 218 cm. H2O (mean 72, median 55). None of the patients had morphological and functional changes of the upper tract, or de novo incontinence postoperatively. CONCLUSIONS: Functioning free muscle transplantation was able to restore voluntary voiding in patients who had previously been dependent on long-term catheterization. Voluntary voiding has been maintained several years postoperatively without deterioration of upper tract function.

Adolescent↗

[Drug therapy of benign prostatic hyperplasia. Is combination therapy with 5 alpha-reductase inhibitors and alpha-receptor blockers effective?].

5 alpha-reductase inhibitors and alpha 1-receptor blockers are the two main drug therapies used in the management of symptomatic benign prostatic hyperplasia. As alpha-reductase inhibitors and alpha 1-receptor blockers act through different mechanisms, a combination of the two agents might be promising. The potential benefits of combination therapy with selective alpha 1-receptor blockers and finasteride, a 5 alpha-reductase inhibitor, are currently being evaluated in several placebo-controlled prospective multicenter studies (VA Study, ALFIN Study, PREDICT Study, and MTOPS Study). The data from these studies available so far demonstrate a statistically significant benefit for the study groups receiving alpha 1-receptor blockers and combination therapy vs placebo and finasteride monotherapy in terms of symptom scores and peak urine flow rates. However, none of the studies yielded a statistically significant advantage of combination therapy over treatment with alpha 1-receptor blockers. These results should be interpreted with reference to the prostatic volume, which in the studies mentioned above was relatively low. From the results of all these studies, it can be concluded that in symptomatic patients with prostate volumes of up to 40-45 ml a combination of 5 alpha-reductase inhibitors with alpha 1-receptor blockers does not appear to provide any benefit. Yet, it can be assumed that in symptomatic patients with prostate volumes of more than 60 ml combination therapy may indeed prove more effective.

5-alpha Reductase Inhibitors↗

[Dihydrotestosterone and the role of 5 alpha-reductase inhibitors in benign prostatic hyperplasia].

The genesis of benign prostate hyperplasia (BPH) depends on two factors: testicular androgen and the aging process. The most important androgen in the prostate is dihydrotestosterone (DHT). In the aging male the level of DHT in the prostate remains largely constant although the plasma level of testosterone decreases. DHT is formed by the reduction of testosterone by the enzyme 5-alpha-reductase, which has two isoenzymes. The 5-alpha-reductase type 2 is the predominant isoenzyme in genital tissue and thus also in the prostate. Finasteride is a 5-alpha-reductase inhibitor, which is applied in the treatment of BHP and male baldness. In the doses used finasteride acts mainly by inhibiting the 5-alpha-reductase type 2, thereby reducing the serum level of DHT by approximately 70% and by about 85-90% in the prostate. Indeed the effect of finasteride in BPH was proven in clinical studies. However, the circulating and intraprostatic DHT could be further reduced by a more effective dual 5-alpha-reductase inhibitor, which would be efficacious in the treatment of benign prostate hyperplasia and other DHT-related disorders.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗

[Contrast-medium enhanced reflux ultrasound in children. A comparison with radiologic imaging up to now].

Voiding cystourethrography (VCUG) has long been the method of choice for the diagnosis of vesicoureteral reflux (VUR). Especially in the course of conservative treatment, the radiation dose involved might become quite high over the years. Since the development of such ultrasound echo-enhancing agents as Levovist (Schering, Germany), we now have the ability to assess the diagnostic efficacy of this agent in the evaluation of VUR with a view to replacing VCUG with the radiation-free ultrasound methodology. A total of 104 children with a mean age of 5.4 years were examined using echo-enhancing ultrasound after informed consent had been obtained from their parents. For control purposes, all children were examined by standard VCUG as well. The diagnosis of VUR was judged to be positive when microbubbles appeared in the ureter or renal pelvis. Correlations were sought between the sonographic findings and those obtained by standard VCUG. In 76 (37%) of the 208 ureter-kidney units investigated, VUR was detected by both technologies. VUR was diagnosed by ultrasonography only in 5 units and by VCUG only only in 3 units. All reflux grades (I-V) were identified. The specificity and sensitivity of the contrast reflux ultrasound were significantly high. The long contrast time of up to 30 min combined with the high contrast effect resulted in convincing images with high levels of diagnostic confidence. Our results clearly demonstrate that the safety and accuracy of the diagnosis of VUR by means of contrast-enhanced ultrasound is statistically comparable to those of standard radiologic VCUG. Therefore, this methodology is an exceptional approach to reducing the number of children being exposed to ionising radiation especially during conservative follow-up of children with reflux.

Adolescent↗

Dihydrotestosterone and the concept of 5alpha-reductase inhibition in human benign prostatic hyperplasia.

The development of human benign prostatic hyperplasia (BPH) clearly requires a combination of testicular androgens and the ageing process. Although the role of androgens as the causative factor for human benign prostatic hyperplasia is debated, they undoubtedly play, at least, a permissive role. The principal prostatic androgen is dihydrotestosterone. Although not elevated in human benign prostatic hyperplasia, dihydrotestosterone levels in the prostate remain at a normal level with ageing, despite a decrease in the plasma testosterone. Dihydrotestosterone (DHT) is generated by a reduction in testosterone. Two isoenzymes of 5alpha-reductase have been discovered. Type 1 is present in most tissues in the body where 5alpha-reductase is expressed, and is the dominant form in sebaceous glands. Type 2 5alpha-reductase is the dominant isoenzyme in genital tissues, including the prostate. Finasteride is a 5alpha-reductase inhibitor that has been used to treat BPH and male-pattern baldness. At doses used clinically, its major effect is to suppress type 2 5alpha-reductase, because it has a much lower affinity for the type 1 isoenzyme. Finasteride suppresses DHT by about 70% in serum and by as much as 85%-90% in the prostate. The remaining DHT in the prostate is likely to be the result of type 1 5alpha-reductase. The suppression of both 5alpha-reductase isoenzymes with GI198745 results in greater and more consistent containment of serum dihydrotestosterone than that observed with a selective inhibitor of type 2 5alpha-reductase. Physiological and clinical studies comparing dual 5alpha-reductase inhibitors, such as GI198745, with selective type 2, such as finasteride, will be needed to determine the clinical relevance of type 1 5alpha-reductase within the prostate. There have been two large, international multicentre, phase III trials published documenting the safety and efficacy of finasteride in treating human benign prostatic hyperplasia. Combining these two studies, randomised, controlled data are available for 12 months. Non-controlled extension of these data from a subset of patients, who elected to continue on the drug for 3, 4 and 5 years, are also available. Long-term medical therapy with finasteride can reduce clinically significant endpoints, such as acute urinary retention or surgery. According to the meta-analysis of six randomised, clinical trials with finasteride, finasteride is most effective in men with large prostates. A more effective dual inhibitor of type 1 and 2 human 5alpha-reductase may lower circulating dihydrotestosterone to a greater extent than finasteride and show advantages in treating human benign prostatic hyperplasia and other disease states that depend on dihydrotestosterone. A clinical evaluation of potent dual 5alpha-reductase inhibitors may help to define the relative roles of human type 1 and 2 5alpha-reductase in the pathophysiology of benign prostatic hyperplasia and other androgen-dependent diseases.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗