Herbert Sperling

Phase II trial of titanocene dichloride in advanced renal-cell carcinoma

Abstract Titanocene dichloride was capable of inhibiting the growth of different types of human tumors in vitro. A total of 14 patients with metastatic renal-cell carcinoma (RCC) received 270 mg/m2 titanocene dichloride every 3 weeks for 6 weeks. Although the toxicities and side effects encountered were mild to moderate, no partial or complete response was detectable. In conclusion, titanocene dichloride has no advantage in the therapy of RCC.

Does penile size in younger men cause problems in condom use? a prospective measurement of penile dimensions in 111 young and 32 older men

OBJECTIVES Young men often complain about problems with condom use, but very little information exists about the influence of mens age on penile dimensions and therefore on possible problems in the use of the most important means of contraception in the young. METHODS We performed a prospective measurement of penile dimensions in 111 men,18 to 19 years old (group A), and in 32 men, 40 to 68 years old (group B). We measured penile length and width in the flaccid state and after visual and manual self-stimulation in group A and after intracavernous injection of prostaglandin E(1) in group B. RESULTS The mean flaccid length in group A (8.60 cm) and group B (9.22 cm) was significantly different. The mean erect length in group A (14.48 cm) and group B (14.18 cm) was not significantly different. The mean flaccid width at the base was significantly different between group A (3.08 cm) and group B (2.87cm), but the mean flaccid width at the glans was not (group A, 3.02 cm; group B, 3.01 cm). The mean erect width at the base (group A, 3.95 cm; group B, 3.50 cm) and the erect width of the glans (group A, 3.49 cm; group B, 3.32 cm) were significantly different. CONCLUSIONS Our assumption that the problems young men experience with condom use may be because of smaller penises could not be proved. To address the problems in condom use in younger men, a larger variety of condom sizes and better information about condom use may be useful.

Management of neurogenic fecal incontinence in myelodysplastic children by a modified continent appendiceal stoma and antegrade colonic enema

OBJECTIVES Antegrade colonic enemas for neurogenic fecal incontinence via reverse reimplanted appendices (Mitrofanoff principle) have been primarily reported by Malone and coworkers in 1990. We used a modification of the described surgical technique and treated the first 10 patients with neurogenic fecal incontinence due to spina bifida. The surgical procedure and the results are reported. METHODS Since November 1991, we have used a surgical procedure similar to the appendiceal continence mechanism in urinary diversion to establish a continent colonic cutaneous stoma for antegrade enemas in 10 myelodysplastic patients (4 females, 6 males; median age 13.2 years [range 6 to 26]) with severe neurogenic fecal incontinence. The average follow-up is now 26.4 months (range 12.5 to 50). All patients had neurogenic bladder dysfunction successfully managed by clean intermittent catheterization, anticholinergic drugs, or artificial sphincter implantation. The surgical technique for fecal incontinence included the partial orthotopic submucosal imbedding of the appendix into a cecal tenia and the fixation of the ileocecal region at the inner side of the abdominal wall after creation of an appendicocutaneous catheterizable stoma. RESULTS All patients reached fecal continence for at least 38 hours (median 45.3) by using antegrade colonic enemas with 1.5% saline solution (n = 9) or GoLYTELY solution (n = 1), 0.5 to 1.5 L every 2 to 3 days. All other therapies (diet, oral medication, rectal purgative, or enema) to reach fecal continence had previously failed. There were only two complications seen at the follow-up. One boy with an artificial urinary sphincter presented with infection of the sphincter system, which led to explantation. Another boy presented 15 months after creation of the colonic appendiceal stoma with saline intoxication possibly due to a homemade saline solution. CONCLUSIONS We conclude that the antegrade colonic enema via an orthotopic continent appendiceal stoma is a safe and highly effective treatment modality for fecal incontinence in patients with neurogenic bowel dysfunction if nonsurgical management has failed.

Sexualität im Alter

ZusammenfassungStörungen der Sexualfunktion und des sexuellen Erlebens bei älteren Menschen führen oft zu einer erheblichen Beeinträchtigung der Lebensqualität. Die epidemiologische Datenlage und die spezifischen Konzepte zu Diagnostik und Therapie dieser Störungen sind noch unzureichend, in jüngster Zeit wurden jedoch vermehrt Untersuchungen vorgenommen. Heute liegen bereits erste Daten vor, die ein wissenschaftlich fundiertes Bild der altersspezifischen Veränderungen erkennen lassen.AbstractDisturbance of sexual function and sexual perceptions in the aging often have a significant negative impact on overall quality of life. Epidemiological data on this phenomenon are sparse. Recently, however, more investigations have been undertaken to improve diagnostic and therapeutic approaches. First scientific concepts are now emerging that will allow better patient care in the future.

The Treatment of Stress Incontinence in Men: Part 2 of a Series of Articles on Incontinence

BACKGROUND Stress incontinence in men is a rare, usually iatrogenic condition. Its prevalence can be expected to rise in the future because of the increasingly common performance of radical prostatectomy. Most men who have undergone prostatectomy experience a transient disturbance of urinary continence. Such disturbances are only rarely due to structural damage to the sphincter apparatus and therefore have a good prognosis for spontaneous recovery. METHOD Selective literature review. RESULTS Pelvic floor training and/or pharmacotherapy can be used for more rapid restoration of subjectively satisfactory urinary continence. If the sphincter is intact, continence can also be regained in the early postoperative period through the submucosal injection of bulking agents. Incontinent patients whose urinary sphincter is dysfunctional because of denervation or direct injury to striated muscle can now be treated with a variety of surgical techniques. The implantation of an artificial sphincter is the gold standard of therapy. Properly selected and informed patients can also be treated with minimally invasive procedures, such as the creation of a male suburethral sling, although the experience with such procedures to date has not been extensive. CONCLUSION Post-prostatectomy incontinence has a good prognosis and should thus be treated conservatively at first. If it nonetheless persists, surgical treatment is indicated for patients who choose it after being fully informed about their options.

New treatment options for erectile dysfunction. Pharmacologic and nonpharmacologic options

Zusammenfassung.Die Therapie der erektilen Dysfunktion (ED) hat sich im Laufe der letzten Jahrzehnte grundlegend gewandelt. Neben der lokalen Applikation von Prostaglandin E1 intraurethral oder intrakavernös befindet sich ein transdermales Präparat in der Entwicklung. Mit Yohimbin steht eine zentral wirksame Substanz zur Verfügung, die insbesondere bei psychogener Ursache der Erektionsstörung als Dauermedikation eingesetzt werden kann. Apomorphin als zentraler Dopaminrezeptoragonist kann vor allem bei leichter bis mittelschwerer ED eingesetzt werden und wirkt bei sublingualer Applikation bereits nach 15–20 min. Sildenafil ist ein selektiver Phosphodiesterase-Typ-5-(PDE-5-)Inhibitor, der sein Wirkungsmaximum bei paralleler sexueller Stimulation nach 60 min erreicht. Eine absolute Kontraindikation ist die Einnahme von Nitraten. Die Erfolgsrate bei ED beträgt in Abhängigkeit von der Ätiologie bis zu 80%. Neu zugelassen sind Vardenafil und Tadalafil, weiterere PDE-5-Inhibitoren. Die Ergebnisse der Zulassungsuntersuchungen zeigen ähnliche Erfolgs- und Nebenwirkungspotentiale wie bei Sildenafil. Pharmakologisch liegen bei Vardenafil eine gegenüber Sildenafil gesteigerte Selektivität und Wirksamkeit vor, derer Auswirkung in der täglichen Praxis ihre Bestätigung finden muss. Tadalafil weist im Gegensatz zu Sildenafil eine andere Pharmakokinetik mit einer Wirkungsdauer von bis zu 24 h auf, die die sexuelle Aktivität in einem größeren Zeitfenster erlaubt.Sollte eine medikamentöse Therapie nicht zum Erfolg führen, so sind sowohl die Vakuumpumpentherapie als auch die Verwendung von Schwellkörperimplantaten Therapieoptionen mit einer hohen Akzeptanz der Patienten und vor allem auch der Partnerinnen.Durch diese therapeutische Vielfalt sollte es möglich sein, unter Zusammenarbeit aller ärztlichen Fachdisziplinen unseren Patienten ein zufrieden stellendes Sexualleben zu ermöglichen bzw. wiederherzustellen.Abstract.Erectile dysfunction is a medical condition that influences the sexual life of millions of men and women worldwide. Due to a large number of currently available drugs, the therapy of erectile dysfunction has changed profoundly during the last decades. The pharmacologic options are divided into initiators versus conditioners and central- or peripheral-acting drugs.Besides intraurethral and intracavernous application of prostaglandine E1 (PGE1, peripheral initiator) – a transdermal application is still in clinical testing –, there are drugs for oral application.PGE1, the vasoactive drug mainly used, was replaced by sildenafil in first-line-therapy. PGE1, administered intracavernosally or intraurethrally, is highly effective with success rates up to 90%, but the attrition rate due to personal inconvenience remains significant.Yohimbine is known as a central amplifier of erection and is useful in psychogenic and mild organic erectile dysfunction. Apomorphine, a central initiator of erection, amplifies erectile response as a central dopamine agonist in mild and moderate erectile dysfunction and starts acting 15–20 min after sublingual application.The phosphodiesterase type 5 (PDE-5) inhibitors sildenafil, vardenafil, and taldalafil are peripheral conditioners. Sildenafil, the most distributed oral agent worldwide, should be taken orally 60 min before sexual intercourse in combination with sexual stimulation. Sildenafil shows a high efficacysafety profile with success rates for all etiologies between 50–80%. Paralleling nitrate-containing medication is an absolute contraindication. Vardenafil, another selective PDE-5 inhibitor with potentially higher selectivity and efficacy compared to sildenafil was just approved. The data from the clinical trials show the same adverse events and success rates as sildenafil. Tadalafil, just launched as well, amplifies erectile function for up to 24 h, allowing the patient to engage in sexual activity for this period. Adverse events and success rates resemble those of the other two substances.If medical treatment fails, there are nonpharmacologic options such as the vacuum constriction device and penile implants. The vacuum device is a safe and effective option for well-selected patients. Penile implants, especially the inflatable ones, completely imitate the physiologic erection. Due to recent research, infection rates and mechanical failures were minimized. Therefore penile implant surgery is well accepted by the patients and their partners.Despite this wide variety of options, therapy of erectile dysfunction should be performed in an individually adapted way. The patients exact history, physical examination, collaboration of medical disciplines and choice of therapy will offer all patients the possibility to achieve or regain a satisfying sexual life.

The Whitaker test, a useful tool in renal grafts?

OBJECTIVES To evaluate the Whitaker test, a pressure flow examination, for its prognostic value in dilated renal transplants because urologic complications, such as ureteral stenosis, are significant problems after kidney transplantation. METHODS Twenty-five patients with obstruction of the renal transplant and subsequent percutaneous nephrostomy were evaluated with a urodynamic pressure flow test (Whitaker test) in combination with antegrade pyeloureterography. The results of the Whitaker test were related to the serum creatinine values. RESULTS The Whitaker test demonstrated normal pressure flow (less than 15 cm H(2)O) in 7 patients, pressure flow between 15 and 25 cm H(2)O in 10, and pathologic results (greater than 25 cm H(2)O) in 8 patients. After percutaneous nephrostomy, the serum creatinine level decreased in 22 of 25 patients, although the urodynamic pressure flow revealed a significant obstruction (Whitaker test greater than 25 cm H(2)O) in only 8 patients. The sensitivity of the Whitaker test to indicate the relevance of post-renal transplant stenosis in comparison to the declining serum creatinine level after successful percutaneous nephrostomy was 79%; the specificity was 50%. CONCLUSIONS The results of our study indicate that a decreasing creatinine level in correlation with radiologic results is the leading finding in dilation of transplanted kidneys without rejection. The Whitaker test, as a pressure flow examination, provided no additional information.

An Extract From the Bark of Aspidosperma Quebracho Blanco Binds to Human Penile α-Adrenoceptors

Purpose: We determined whether an extract from the bark of the tree Aspidosperma quebracho blanco, which is used as a prescription drug to treat erectile dysfunction in some countries, can bind to human penile α1 and α2-adrenoceptors, and cloned human α-adrenoceptor subtypes.Materials and Methods: Competition binding studies were performed with α1 and α2-adrenoceptors with the extract and 4 subfractions prepared from it using [3H]prazosin (New England Nuclear, Dreieich, Germany) and [3H]RX 821002 (2-methoxy-idazoxam) (Amersham, Braunschweig, Germany) as the radioligands, respectively.Results: In a concentration dependent manner the extract inhibited 2-methoxy-idazoxam binding to human penile α2-adrenoceptors. Somewhat less potently it inhibited [3H] prazosin binding to penile α1-adrenoceptors. The extract also inhibited binding to cloned α2-adrenoceptors more potently than to α1-adrenoceptors but did not discriminate among subtypes. Subfraction B was more potent than the others for all cloned α1-adrenocep...

Cryptorchidism: fowler-stephens procedure or autotransplantation-a new experimental model.

OBJECTIVES To investigate the effect of different operative procedures on testicular development in cryptorchidism. METHODS One hundred ten postpubertal Wistar-WU rats were divided into four groups. Group 1 (35 rats) underwent microsurgical autotransplantation of the right testis with end-to-end anastomosis of the testicular vessels. Group 2 (35 rats) underwent the Fowler-Stephens maneuver with intra-abdominal fixation of the testis. To determine the influence of temperature on testicular development, group 3 (35 rats) underwent the Fowler-Stephens maneuver with scrotal replacement of the testis. Group 4 (5 rats) was a control group without operative treatment. To assess the early and late changes of testicular ischemia and reperfusion, groups 1 to 3 were divided into seven subgroups (5 rats each) with defined postoperative intervals (0.5 hour, 2 hours, 4 hours, 8 hours, 16 hours, 14 days, and 60 days). Testicular development, sperm density, pH value, tissue lactate concentration, and tubular diameter were the parameters used to determine success or failure. RESULTS After autotransplantation, testicular development exhibited an atrophy rate of less than 50% and a significant decrease in groups 2 and 3 after 60 days. The sperm density was significantly different between groups 2 and 4 (control). The pH value was significantly different after 2 hours in groups 2 and 3. The tissue lactate concentration revealed no significant differences. The tubular diameters were significantly diminished in group 2 after 60 days. CONCLUSIONS The smaller atrophy rate of the testes suggests that we successfully established a model in the rat to compare the operative outcome after autotransplantation and the Fowler-Stephens procedure in cryptorchidism. The significant difference in the tubular diameters for the intra-abdominally placed testes might be caused by the exposure of the testis to a higher temperature.

Behandlung und Verlauf von Patienten mit Plattenepithelkarzinom des Penis

ZusammenfassungAufgrund des seltenen Auftretens des Peniskarzinoms existieren keine prospektiven Untersuchungen zur Therapieoptimierung. Deshalb stellen sich Fragen nach einer Verbesserung der operativen Therapie des lokal fortgeschrittenen Karzinoms und einer Behandlung bei Systemerkrankung. Auf der Basis unserer Erfahrungen in der Behandlung von 22 Patienten mit Peniskarzinom haben wir folgende Therapiekonzepte entwickelt. Im klinisch begrenzten Stadium (T1-2N0M0) erfolgte die Teilamputation des Penis bei 10 Patienten. Die Dreijahresüberlebensrate betrug 90 %. Bei lokal fortgeschrittener Erkrankung (T3–4 oder N1–3) wurde zunächst die Entfernung des Primärtumors durch eine Teilamputation oder Penektomie durchgeführt. Nach 4 wöchiger antibiotischer Vorbehandlung erfolgte die inguinale Lymphadenektomie beidseits, die bei positiven Lymphknoten auf eine pelvine Lymphadenektomie ausgedehnt wurde. Bei Ulzeration der Haut erfolgte die En-bloc-Entfernung mit Schwenklappenplastik [Fascia tensor lata (n = 2) oder Rectuslappenplastik (n = 1) ]. Die Dreijahresüberlebensrate betrug im Tumorstadium T1–2N1M0 (n = 4) 67 % und im Tumorstadium T3–4N1–3M0 (n = 8) nur 25 %. Bei systemischem Tumorprogreß erfolgt eine induktive Polychemotherapie mit Cisplatin, Bleomycin und Methotrexat. Wir erzielten bei 9 Patienten eine objektive Ansprechrate von 22 % (1 CR, 1 PR). Nach unseren Ergebnissen bietet nur die radikale Operation in niedrigen Tumorstadien unter Resektion der inguinalen Lymphknoten die Chance auf eine Heilung.SummarySince squamous cell carinoma of the penis is rare, prospective trials do not exist. Therefore, new treatment strategies have to be developed. Based on our experience with the treatment of 22 patients with penile squamous cell carcinoma, we describe our therapeutic approaches. Ten patients with superficial disease (T1-2N0M0) were treated with partial penectomy. The 3-year survival rate amounted to 90 %. In patients with extensive disease (T3-4 or N1-3) a partial or total penectomy was performed. After initial antibiotic therapy for 4 weeks, patients underwent inguinal lymph-node dissection and if the nodes were positive, additional pelvic lymph-node dissection. In patients with ulcerous inguinal lymph-node metastases surgical resection was performed, covering the wound with a musculocutaneous flap (tensor fascia lata flap n = 2; rectus abdominis flap n = 1). The 3-year survival rate of patients with T1-2N1 tumours (n = 4) was 67 % and with T3-4N1-3 (n = 8) 25 %. Patients with distant metastases received inductive systemic chemotherapy with cisplatin, methotrexate and bleomycin. Objective responses occurred in 22 % (1 CR, 1 PR) of 9 patients. These results suggest that immediate radical surgery with lymph-node dissection is the best treatment for squamous cell carcinoma of the penis.