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Biomedical subjects

S C Müller

Publications and source records attributed to S C Müller.

At least 19 recordsLinked to original sources

Traveling waves in yeast extract and in cultures of Dictyostelium discoideum.

Biological self-organization was investigated in a biochemical and a cellular system: yeast extract and cultures of the slime mold Dictyostelium discoideum. In both systems traveling reaction-diffusion waves occur in response to oscillatory reactions. Glycolytic degradation of sugar in a yeast extract leads to the spontaneous formation of NADH and proton waves. Manipulation of the adenine nucleotide pool by addition of purified plasma membrane ATPase favors the formation of both reaction-diffusion waves and phase waves. The results indicate that the energy charge has an important impact for the dynamics of glycolytic patterns. When affecting the lower part of glycolysis by pyruvate addition the frequency of wave generation was increased with concomitant formation of rotating NADH and proton spirals. During morphogenesis of the cellular system Dictyostelium discoideum, circular and spiral shaped aggregation patterns of motile amoeboid cells form in response to traveling cAMP waves. Velocity analysis of the cell movements reveals that the cAMP waves guide the cells towards the site of wave initiation along optimized trajectories. The minimization of aggregation paths is based on a mechanism exploiting general properties of excitation waves. The resulting aggregation territories are reminiscent of Voronoi diagrams.

Animals

[Indications for nuclear medicine therapy in advanced prostate carcinoma].

For patients with advanced prostate cancer efficient therapy of painful bony lesions is the primary goal of interdisciplinary treatment strategies. Preservation of quality of life appears to be the main aim rather than prolongation of life. Apart from oral pain relief and local irradiation systemic treatment with radionuclides offers low-risk radiotherapeutic strategies for the palliation of painful, multifocal osteoplastic bone metastases. Depending on the radiopharmaceutical substance chosen response and reduction of pain are described in 65-80%. The duration of pain relief lasts between 6-12 weeks. During this time the morphine based medication can be reduced and in some cases withdrawn which positively effects quality of life. After improvement of myelosuppression treatment with radionuclides can be repeated. Patients have to be hospitalized for two days because of protection from radiation procedures.

Bone Neoplasms

[Testicular tumors. Mortality and recurrence after inadequate therapy].

From 1983 to 1994, 293 patients with testicular germ cell tumors were treated at the Department of Urology, Bonn University, Germany. 252 patients (86%) were available for follow-up studies. 17/252 (6.8%) of patients died of disease, 41/252 (16%) had a tumor recurrence after complete remission. 20/41 (49%) patients with recurrence, who mainly had been referred for further treatment, had been treated inadequately. Inadequate treatment consisted of surgical failures after orchiectomy, incomplete retroperitoneal lymph node dissection after chemotherapy, delay of treatment, and inadequate chemotherapy. 80% of recurrences were found within the first two years after treatment, late relapses were found in 3.6%. Early recurrences were mainly pulmonary, late recurrences mostly occurred in the retroperitoneum or atypical. 20% of all recurrences were local recurrences.

Adult

Idiopathic anterior urethritis in prepubertal and pubertal boys: pathology and clues to etiology.

OBJECTIVES: Records were reviewed to examine the common features of boys with noninfectious anterior urethritis, and to describe the underlying pathology. METHODS: Five cases of anterior urethritis with features typical of this syndrome are reviewed. RESULTS: These cases demonstrate the typical appearance and in 1 case the pathologic diagnosis of squamous metaplasia of the bulbar urethra. CONCLUSIONS: Prepubertal urethrorrhagia is associated with squamous metaplasia of the urethra. The tendency to stricture formation may precede instrumentation of the urinary tract.

Adolescent

Efficacy and safety of transurethral alprostadil therapy in men with erectile dysfunction. MUSE Study Group.

OBJECTIVE: To examine the safety and efficacy of transurethral pharmacotherapy for erectile dysfunction, involving the use of a novel therapeutic system to administer alprostadil (prostaglandin E1) to the urethral mucosa in a double-blind, randomized, parallel, placebo-controlled study conducted in five countries in Europe. PATIENTS AND METHODS: In an outpatient setting, patients with primarily organic erectile dysfunction of at least 3 months' duration were treated with transurethral alprostadil, in an open-label, dose-escalating study. Testing stopped when the dose provided an erection sufficient for intercourse, as assessed by the patient and the investigator. Patients who achieved a sufficient response were then randomized to either active medication at the selected dose or to placebo for use at home for 3 months. After each home administration, patients recorded in diaries whether or not sexual intercourse occurred and any adverse reactions to the drug. RESULTS: A total of 249 patients were treated in an outpatient setting; of these patients, 159 (64%) achieved an erection sufficient for intercourse and were randomized (1:1) to either active medication or placebo for home treatment. Of the patients randomized to alprostadil for home treatment, 69% reported intercourse at least once, compared with 11% of patients randomized to placebo (P < 0.001). The most common adverse reaction, urethral pain/burning, was reported by 7% of patients in the clinic. Most patients (83%) graded transurethral alprostadil as causing minimal or no discomfort in the clinic. No patient reported priapism or developed penile fibrosis. CONCLUSION: Alprostadil delivered transurethrally by this system was well tolerated and effective in treating erectile dysfunction.

Adult

The effect of transurethral alprostadil on the quality of life of men with erectile dysfunction, and their partners. MUSE Study Group.

OBJECTIVE: To evaluate the impact of treatment for erectile dysfunction on the quality of life of men and their partners. PATIENTS AND METHODS: The study included 249 men with organic erectile dysfunction of more than 3 months' duration who self-administered transurethral alprostadil in an open-label, dose-escalating manner in an outpatient medical setting. Patients with a sufficient response (159) were randomly assigned in a double-blind protocol to either active medication or placebo for 3 months at home. Patients and partners each completed quality-of-life questionnaires before and after treatment. RESULTS: In the clinic 159 of the 249 men (64%) had an erection sufficient for intercourse when using transurethral alprostadil. At home, 46 of 67 men (69%) reported intercourse at least once on transurethral alprostadil, compared with eight of 73 (11%) on placebo (P < 0.001). Patients on alprostadil showed a 34% improvement in their 'relationship with partner', a 5% improvement in 'personal wellness', and a 71% improvement in 'quality of erection' domains, compared with a decline of 11%, 8% and 1%, respectively, in patients on placebo (P < 0.005 for each comparison). Partners of patients on alprostadil showed a 35% improvement in the 'relationship with partner' domain, compared with a 12% improvement in the placebo group (P = 0.028). There was a trend toward improvement in other partner domains. Urogenital pain was reported by 14% of patients during home treatment. CONCLUSION: The resumption of sexual intercourse with the use of transurethral alprostadil was accompanied by an improvement in several important quality-of-life domains in patients and their partners.

Adult

[Urinary incontinence in neurogenic defects and urogenital anomalies in childhood].

Dysraphic defects may cause neurogenic incontinence in childhood. Constipation and encopresis are often associated. Depending on the involved segment of the spinal cord hyperreflexia or atonia of the detrusor is observed. Similar findings, without anatomic correlation, can be seen in occult-neurogenic voiding dysfunctions. Therapeutic means aim at preservation of kidney function and the best possible continence. If the symptoms cannot be treated by anticholinergic drugs in a low-capacity, hypertonic bladder, augmentation by bowel segments or continent urinary diversion (e.g. Mainz I pouch) is performed. In the last years modalities of clean intermittent self-catheterization in high-capacity, atonic bladders could be enhanced by the development of new atraumatic catheter systems. Urogenital malformation e.g. proximal epispadias and exstrophic bladder can cause incontinence as well. Recently, new therapeutic concepts were introduced. Ectopic ureter (extraurethral incontinence) in girls or posterior urethral valves in boys as a reason for incontinence must not be forgotten.

Child

MIB-1 immunohistochemistry in clinical stage I nonseminomatous testicular germ cell tumors predicts patients at low risk for metastasis.

BACKGROUND: The clinical Stage I of nonseminomatous germ cell tumors (NSGCT) is inaccurate in 30% of patients. In previous studies on tumor biologic risk factors, low tumor proliferation rates predicted a group of patients at low risk for occult metastatic disease. The goal of this study was to confirm the immunohistochemical assessment of tumor proliferation using MIB-1 (Ki-67 receptor) in a different patient cohort with different investigators to prove the method's reliability. METHODS: Orchiectomy specimens of 78 patients with clinical Stage I NSGCT (50 patients with pathologic Stage I and 28 patients with pathologic Stage II disease, all patients underwent retroperitoneal lymph node dissection) were retrospectively analyzed by histopathologic reevaluation and MIB-1 immunostaining. RESULTS: Mean MIB-1 values between the two pathologic stages differed significantly (51.5% MIB-1 positive tumors cells in pathologic Stage I and 75.1% MIB-1 positive tumor cells in pathologic Stage II disease; P = 0.02). Using a 70% cutoff value, pathologic stages were correctly classified in 69% of cases (sensitivity of 86%, specificity of 60%, negative predictive value of 88%, and positive predictive value of 55%). Compared with traditional risk factors such as percentage of embryonal carcinoma and vascular invasion, in multivariate analysis, MIB-1 was the best predictor of patients at low risk for metastasis. CONCLUSIONS: This study in a different patient population with different investigators confirmed previous results of MIB-1 staining to predict a group of patients with clinical Stage I NSGCT who were at low risk for metastasis. The method is simple and reproducible to improve risk classification in low stage testicular carcinoma. Using this technique, a group of patients at very low risk for metastasis can be identified. [See editorial counterpoint on pages 1641-5 and reply to counterpoint on page 1646, this issue.]

Antibodies, Monoclonal

Self-induced splitting of spiral-shaped spreading depression waves in chicken retina.

Spreading depression (SD) of electroencephalographic activity is a dynamic wave phenomenon in the central nervous system (CNS). The retina, especially the isolated chicken retina, is an excellent constituent of the CNS in which to observe the dynamic behavior of the SD wave fronts, because it changes its optical properties during a SD attack. The waves become visible as milky fronts on a black background. It is still controversial what the basic mechanistic steps of SD are, but certainly SD belongs to the self-organization phenomena occurring in neuronal tissue. In this work, spiral-shaped wave fronts are analyzed using digital video imaging techniques. We report how the inner end of the wave front, the spiral tip, breaks away repeatedly. This separation process is associated with a Z-shaped trajectory (extension approximately 1.2 mm) that is described by the tip over one spiral revolution (period 2.45+/-0.1 min). The Z-shaped trajectory does not remain fixed, but performs a complex motion across the retina with each period. This is the first time, to our knowledge, that established imaging methods have been applied to the study of the two-dimensional features of SD wave propagation and to obtaining quantitative data of their dynamics. Since these methods do not interfere with the tissue, it is possible to observe the intrinsic properties of the phenomenon without any external influence.

Animals

[Treatment of benign prostatic hyperplasia with alpha 1-adrenoreceptor antagonists].

The International Consensus Committee recommends alpha-adrenoceptor antagonists for medical therapy benign prostatic hyperplasia (BPH). This review evaluates 52 randomized, placebo-controlled, double-blind studies, including 10399 patients and, moreover, 40 clinical studies including 33600 patients undergoing treatment with alpha-adrenoceptor antagonists because of BPH. The therapeutic efficacy of all alpha-adrenoceptor antagonists is more or less the same. There is an average improvement of symptom scores of about 35% and a mean increase in maximum flow rate of between 1.8 and 2.5 ml/s. Studies investigating long-term efficacy and quality of life tend to show a long-term benefit. The introduction of selective alpha 1-adrenoceptor antagonists led to a significant reduction of side effects. These side effects are primarily caused by the vasodilatatory qualities of alpha-blockers. The development of so-called uroselective alpha 1A-adrenoceptor antagonists in the treatment of BPH possibly leads to further reduction of side effects related to vasodilatation. Medical therapy by alpha 1-adrenoceptor antagonists seems to be superior to phytotherapy or treatment with 5 alpha-reductase inhibitors, as shown in a few studies. So far, it is not clear whether there is any advantage of combination therapy. The application of alpha 1-adrenoceptor antagonists is indicated in all cases of symptomatic BPH, excluding patients who need TUR-P (e.g., middle lobe) or prostatectomy. If patients are either willing or eligible to have surgical treatment, therapy by alpha 1-adrenoceptor antagonists is a rational choice. Comparative clinical trials have to be conducted to provide additional information and to clarify which alpha-blocker may be recommended as the first choice. Until then, those alpha 1-adrenoceptor antagonists should be used for which safety and efficacy are well documented and which can be prescribed at reasonable costs.

Adrenergic alpha-1 Receptor Antagonists

Management of complete ureteral replacement. Experiences and review of the literature.

The common treatment for patients with extensive damage to the ureter is complete ureteral replacement, combining Boari flap-psoas bladder hitch and downward mobilization of the involved kidney, with complete ideal replacement of the ureter, renal autotransplantation, of elective nephrectomy. Three case reports serve to describe two options of reconstructive treatment for complete ureteral replacement. The operative techniques, their limits, their postoperative results, and the treatment alternatives are discussed with due regard to recent literature. In the case of ileal replacement we have used a very short ileal segment to reduce the absorption surface of the ileal mucosa. Reflux prevention of the ileal segment was performed by creating an invaginated distal ileum nipple which was additionally fixed at the Boari flap by a third stapler row (auto suture TASS) to prevent potential nipple-gliding.

Adult

Rhenium-186 HEDP: palliative radionuclide therapy of painful bone metastases. Preliminary results.

The aim of this study was to evaluate the efficacy of rhenium-186 hydroxyethyledine diphosphonate (Re-186 HEDP) for pain relief in patients with disseminated bone metastases primarily from prostate or breast cancer. Up to now, 44 patients taking analgesics were entered in this study and received one or more injections of 1295 MBq of Re-186 HEDP. An analgesic effect of more than 20%, evaluated by using a verbal rating scale (VRS) and a visual analogous scale (VAS), was defined as significant and could be achieved in 60% of these patients. Duration of clinical response averaged 1-4 months (median 5.5 weeks). Side effects such as a moderate decrease of platelets or an increase of pain for 1-2 days (flare-up effect) were observed. Radioactive treatment with Re-186 HEDP appears to be a useful compound for the palliation of painful skeletal metastases and improvement of the remaining quality of life.

Bone Neoplasms

Traveling NADH and proton waves during oscillatory glycolysis in vitro.

Propagation and mutual annihilation of circular and spiral NADH and proton waves were detected by spatially resolved spectrophotometry and fluorescent proton indicators in a biological in vitro system: an organelle-free yeast extract. Spontaneous wave generation during glycolytic sugar degradation is established after an induction period of about 1 h. Controlled wave initiation could be performed by local injection of the strong activator of phosphofructokinase, fructose 2,6-bisphosphate. A crucial role for wave initiation and control of pattern dynamics is attributed to the key enzyme of glycolysis, the allosterically regulated phosphofructokinase. An overall increase in the concentration of its positive effector AMP leads to the formation of rotating spirals. The dynamics of the observed wave patterns resemble that of self-organized calcium waves as recently found in frog eggs and heart cells.

Cell-Free System

Epithelioid leiomyoma of the prostate.

We report a case of an unusual mesenchymal tumor of the prostate. Rectal-digital palpation and transrectal ultrasound showed a circumscribed and inhomogeneous tumor within the right prostatic lobe. Surgical treatment consisted of transurethral resection of the right prostatic lobe. On the basis of morphology and immunohistochemical detection of desmin and smooth-muscle-type actin, the diagnosis of an epithelioid leiomyoma was made. This is the first report of this entity in the prostate. A definite prediction of the biological potential is currently not yet possible.

Humans

Long-term results of internal urethrotomy.

PURPOSE: A retrospective analysis was done of long-term results of internal urethrotomy to evaluate risk factors of stricture recurrence. MATERIALS AND METHODS: Followup studies were performed of 937 patients with urethral strictures treated with internal urethrotomy. Of the patients 357 were treated at Mainz University between 1977 and 1989 (mean followup 4.6 years) and 580 were treated at Bonn University between 1974 and 1986 (mean followup 3.2 years). RESULTS: Strictures recurred in 96 of 357 (26.9%) and 260 of 580 (44.8%) patients, respectively. Risk factors for recurrence were etiology (post-transurethral resection and inflammation), stricture longer than 1 cm. and postoperative catheter drainage for longer than 3 days. CONCLUSIONS: Urethroplasty should be considered in patients at high risk for stricture recurrence and with more than 1 treatment failure after urethrotomy.

Adolescent

Hormone therapy prior to radical prostatectomy in patients with clinical stage C prostate cancer.

Seventy patients with clinical stage C carcinoma of the prostate were treated for 3 months with the gonadotropin-releasing hormone analog, goserelin acetate (Zoladex; Zeneca Pharmaceuticals, Macclesfield, UK) plus an antiandrogen (flutamide). Based on digital rectal examination (DRE), reductions of the size of the prostate and the tumor were noted in 91.4% of patients. Ultrasound demonstrated a decrease in prostatic volume between 0% and 62.5% (median 31%). Prostate-specific antigen (PSA) levels (Hybritech) decreased substantially (mean PSA of 31.3 ng/ml before, to a mean PSA of 1.4 ng/ml after hormonal treatment). A total of 64 patients subsequently underwent radical retropubic prostatectomy. Pathologically, only 9 patients (14.1%) had organ-confined disease (stage B), 34 (53.1%) had stage C tumors, and 21 (32.8%) had positive lymph nodes (stage D1). In 5 patients with nodal metastasis and 7 patients with seminal vesicle invasion, PSA levels after pretreatment were below 0.5 ng/ml. Maximal androgen blockade for a period of 3 months in clinical stage C prostate cancer induces a notable reduction in prostate size ("downsizing"). A "downstaging" effect, as suggested by DRE, ultrasound, and PSA, was not observed. Prospective studies with this treatment regimen should concentrate on a possible benefit concerning local and distant cancer control and survival.

Chemotherapy, Adjuvant