Pilot study of the transdermal application of testosterone gel to the penile skin for the treatment of hypogonadotropic men with erectile dysfunction

Androgens influence important central and peripheral mechanisms of the erectile system. The relevance of a moderate decrease of serum testosterone level for erectile dysfunction (ED) has not been clarified so far. The aim of our study was to offer an easy transcutaneous method of androgen application. A previous study on the pharmacokinetic profile of the testosterone gel applied, showed marked elevation of the serum levels of testosterone. In our study, 46 hypogonadal patients with ED and total lack of vaginal penetration applied testosterone gel (4 mg/day; supplied by Azupharma, Germany) to the penile skin twice a day over 6–8 weeks, after a run-in period with placebo gel of 2 weeks. All patients showed decreased testosterone serum levels (<3 ng/ml) in at least two morning samples over a period of 3 weeks before treatment. Psychogenic etiology was excluded by a sexual psychologist. Patient age was 37–69 years (mean 53.5). Three patients (6.5%) responded to placebo in the run-in phase and were withdrawn from further treatment. Fifteen patients (32.6%) showed improved erection, allowing penetration and sexual intercourse. Twenty-eight patients (60.9%) did not respond to therapy. Local genital skin irritation was not observed. Elevation of peripheral testosterone was not correlated to a positive therapy response. A success-rate of 32.6% in this group of patients after exclusion of psychogenic patients and placebo-responders seems to justify further investigations. A medication period of 6–8 weeks is most probably too short to induce imaginable regenerative effects of testosterone on the erectile system. We therefore suggest that future double-blind and placebo-controlled studies should be designed for a minimum of 3 months. Testosterone gel may be a cost effective form of androgen administration.     

CORRELATION BETWEEN THE NUMBER OF MITOTIC FIGURES AND THE PERCENTAGE OF Ki67-POSITIVE CELLS IN NON-HODGKIN’S LYMPHOMAS

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Breast and axillary tissue MR imaging: correlation of signal intensities and relaxation times with pathologic findings

We tested a variety of inversion-recovery (IR) and spin-echo (SE) sequences by imaging the breast masses of 22 patients before surgery and 23 tissue specimens with magnetic resonance (MR) imaging at 0.6 T to determine the most effective pulse sequences to evaluate breast disease. An SE pulse sequence using a long repetition time (TR) of 1,600 msec and a long echo time (TE) of 90 msec was found to be the most sensitive in depicting carcinoma in the excised tissue specimens, with all of the carcinomas (n = 15) demonstrating irregular areas of higher signal intensity (SI) than that of the adjacent fat. However, only five of 11 breast carcinomas present in the preoperative patients produced a higher SI than that produced by fat on the same T2-weighted sequence. Five of the remaining six carcinomas in the preoperative patients appeared as localized distortions of fibroductular architecture on both T2-weighted SE and IR sequences. In axillary tissue specimens, both metastatic carcinoma and hyperplastic lymph nodes produced a high SI on T2-weighted SE sequences. However, metastatic carcinoma had a significantly longer T2 relaxation time than did hyperplastic lymph nodes.     

Effect of oxidants on proteases of the fibrinolytic system: possible role for methionine residues in the interaction between tissue type plasminogen activator and fibrin.

Evidence has recently been presented that activated macrophages (M phi) express both urinary (u-PA) and tissue type (t-PA) plasminogen activator. Major cell products of M phi and polymorphonuclear neutrophils (PMN) are reactive oxidants of the HOCl/chloramine type. Since PMN and M phi are involved in inflammatory and fibrinolytic processes, we were interested in the interaction of u-PA, t-PA, and plasmin with oxidants of the leukocyte type. The enzymes were treated with chloramine-T, which at pH 8.5 is a selective oxidant for methionine residues. Oxidation by chloramine-T of t-PA abolishes about 40% of both stimulation susceptibility of t-PA by fibrinogen degradation products (FDP) and affinity of t-PA to FDP. However, the plasminogenolytic and amidolytic activity of unstimulated t-PA as well as the plasminogenolytic activity of u-PA and the amidolytic activity of plasmin are not impaired. Identification of the amino acid residues in the t-PA responsible for the interaction with fibrin might be of great importance in order to understand the mechanism of the clot- selectivity of t-PA. The present study gives evidence that fibrin specificity of t-PA partly depends on chloramine oxidizable amino acids, presumably methionine residues. Hence, experimental data on the interaction between t-PA and fibrin, using oxidized and labelled t-PA should be interpreted with caution. It may be suggested that oxidants of the leukocyte type might regulate t-PA activity and selectivity for fibrin.     

Corpus cavernosum autoinjection therapy: initial experiences in erectile dysfunction

The cause of erectile dysfunction was evaluated by a multidisciplinary approach in 120 impotent patients. Out of these, the CCAT was proposed to 20 patients with vasculogenic erectile dysfunction, 19 of them accepted this therapy. The dosage of phentolamine mesylate-papaverin hydrochloride injection required was determined in each patient individually. Usually we injected initially 1 cc in one corpus cavernosum. Eighteen patients followed the regimen successfully at home. In 2 patients prolonged erections were observed, which were successfully relieved by simple corpus puncture, however, discontinuation of therapy was not necessary. CCAT failed in 1/19 patients with a severe venous leak. Follow up was carried out weekly.