Role of surgical thoracic sympathetic interruption in treatment of facial blushing: a systematic review.

OBJECTIVES: This paper aims to review the evidence to support the effectiveness of sympathectomy as a treatment for facial blushing in terms of relief of facial blushing, patient satisfaction, recurrence of blushing, patients regretting treatment and its associated complications. METHODS: A systematic search strategy was performed in Ovid-Medline, Embase, Cochrane library and NICE. Studies reporting outcomes of sympathetic interruption in the treatment of facial blushing were retrieved. RESULTS: Nine studies met the inclusion criteria with 1369 patients included in the final analysis. The age range of patients was 8 to 74 years (from 7 studies) with 56% females. Mean follow up was 21 months in 8 studies (range 6 to 30 months). The pooled proportion of patients who had good relief of facial blushing was 78.30% (95% C.I. 58.20% - 98.39%). Complete satisfaction was reported in 84.02% (95% C.I. 71.71% - 96.33%). Compensatory sweating and gustatory sweating were the commonest complications occurring in 74.18% (95% C.I. 58.10% - 90.26%) and 24.42% (95% C.I. 12.22% - 36.61%) respectively. The estimated proportion of patients regretting surgery was 6.79% (C.I 2.08% 11.50%). CONCLUSION: Sympathetic interruption at T2 or T2-3 ganglia appears to be an effective treatment for facial blushing. However, lack of randomized trials comparing sympathetic interruption with non-surgical methods of treatment and heterogeneity of included studies with respect to assessment of outcome measures preclude strong evidence and definitive recommendations.

[A pill for the man? Current status of fertility control in the man]. / Pille für den Mann? Aktueller Stand der Fertilitätskontrolle beim Mann.

Taking all facts into consideration from animal experiments and clinical studies with regard to the development of a male contraceptive you must be aware that the 'pill for men' will hardly be available in this century. Because of the increasing interest of the industry and the effort of the WHO and other similar institutions, like the Population Council of New York, to develop a male pill the stagnation of the past 20 years could be overcome, and it may be possible to have an adequate method in 2005. In all probability this will be a combination of hormones either from a gestagen plus testosterone preparation or a potent LHRH agonist and/or antagonist, also in combination with a long-acting testosterone preparation, with testosterone levels within the normal range. Nowadays it cannot be said which role gossypol will finally play. There are studies going on with gossypol with some promising results.

Effect of active immunization against luteinizing hormone-releasing hormone on the androgen-sensitive Dunning R3327-PAP and androgen-independent Dunning R3327-AT2.1 prostate cancer sublines.

BACKGROUND: The objective of this study was to determine the effect of active immunization against LHRH on the growth characteristics and histology of subcutaneously implanted tumors of the androgen-sensitive Dunning R3327-PAP and androgen-independent R3327-AT2.1 rat prostate adenocarcinoma sublines. RESULTS: We herein demonstrate that 1) active immunization with an LHRH-diphtheria toxoid-conjugate (LHRH-DT) leads to the downregulation of gonadotropins and testosterone and consequently the atrophy of testosterone-dependent organs such as the testes, prostate, and androgen-sensitive Dunning R3327-PAP tumors, 2) growth inhibition of Dunning R3327-PAP tumors is caused by suppression of cell division rather than by an increase in cell death and is associated with an increase of the tumor stroma content, and 3) volume increase of the androgen-independent Dunning R3327-AT2.1 tumor is slightly but significantly reduced, indicating a local stimulatory LHRH loop within this tumor cell line.

Influence of Escherichia coli on motility parameters of human spermatozoa in vitro.

The influence of E. coli on human sperm motility was studied in vitro. Semen samples were prepared by a swim-up technique and adjusted to 22 x 10(6) spermatozoa/ml. Samples were then inoculated with different concentrations of a uropathogenic strain of E. coli, serotype 06, with initial sperm/bacteria ratios varying between 10:1 and 10000:1. Motion parameters were analysed by computer-aided motility analysis directly, and 2, 4 and 6 h after inoculation. In a second series of experiments, bacterial replication was inhibited by addition of chloramphenicol. In a third series, the effect of E. coli culture filtrates on sperm motility was investigated. The direct inhibitory effect of E. coli on progressive motility of spermatozoa was found to depend upon the bacterial concentration. A distinct inhibitory effect was observed only at a sperm/bacteria ratio of approximately 1, achieved by growth of E. coli during the experiments. For modality of motion, no distinct changes were observed. When growth of bacteria was prevented by chloramphenicol, no inhibitory effect on sperm motility was detected. Sperm motility was not inhibited by E. coli culture filtrates. Analysis by electron microscopy revealed multiple adhesions of E. coli to spermatozoa, causing variable ultrastructural damage as probable morphological correlates of immobilization.

The effect of active immunization against gonadotropin-releasing hormone on the ultrastructure of the rat ventral prostate.

To evaluate the effects of active immunization against gonadotropin-releasing hormone (GnRH) on the ultrastructure of the rat ventral prostate, male Sprague-Dawley rats received three consecutive intramuscular injections of 10 micrograms/100 g body weight (D-Lys6)-GnRH-diphtheria toxoid conjugate (GnRH-DT vaccine). Following immunization, test animals developed sufficiently high antibody titres to block the pituitary gonadal axis. Consequently testosterone values dropped to the levels in castrates. This therapy leads to atrophy of the prostate. Following immunization a strong immunological response, indicating the presence of considerable amounts of a GnRH-like peptide, was observed in the ventral prostates as early as 14 days after the first injection of GnRH-DT. Immunoneutralisation of GnRH-like activity may contribute to the effects observed.

Intravasal application of BCG (Bacille Calmette Guerin) is not an effective method for control of fertility in the male: a preliminary report.

Bacille Calmette Guerin (BCG) was applied intravasally in male rats with the hope of developing a method for control of fertility in the male. Our results, however, suggest that this approach is not feasible for control of male fertility.

PIP: Some researchers had proposed earlier that Bacille Calmette Guerin (BCG) injected intratesticularly would cause an autoimmune response against haploid spermatogenic cells, thereby bringing about azoospermia. Yet, research showed that the injection caused transient scrotal swelling and pain. So urologists from Salzburg, Austria, General Hospital conducted laboratory research to determine the feasibility of intravasal administration of BCG in controlling male fertility. They used a catheter to administer BCG (1 million bacilli) into the lumen of the vas deferens of 12 adult male rats (220-240 gm). The spermatozoa removed from the affected vas deferens had normal morphology and their motility was normal. This technique did not cause any granuloma formation. The histological features of the testis, epididymis, and vas deferens on the side where BCG was administered were identical to the normal features of the same organs on the other side. None of the organs exhibited any inflammatory reactions. These results indicated that BCG cannot control male fertility.

Effect of active immunization to luteinizing-hormone-releasing hormone on the fertility and histoarchitecture of the reproductive organs of male rat.

The feasibility of using a vaccine against luteinizing-hormone-releasing factor for suppression of pituitary and gonadal functions has been indicated for some time. Antibody production against this low-molecular-weight, naturally occurring decapeptide, however, requires to be coupled to a carrier protein to enhance its immunogenicity. LHRH was coupled to diphtheria toxoid (DT). Adult male Sprague-Dawley rats with a mean basal body weight of 200 g were immunized with anti-LHRH-DT (20 micrograms/injection/rat) at four-week intervals. An equal number of unexposed animals served as controls. Six animals were killed every two weeks up the end of the week 43. The vaccination schedule did not have any effect on the gain in body weight, nor was any adverse effect of vaccination observed in the course of the investigations. The pituitary, prostate, epididymis, testes, seminal vesicles, adrenal and thyroid were excised for determination of organ weight and histological examination. The adrenal, pituitary and thyroid showed no remarkable weight changes during the observation period, whereas the weights of the reproductive organs demonstrated significant reductions compared to those of the control group. The histopathology revealed marked to significant changes in the gonads and the accessory sex organs including the prostate. A progressive phase of regeneration of spermatogenesis was evident 98 days after vaccination. Total recovery of spermatogenesis was observed 300 days after vaccination. The mating studies showed the return of fertility 300 days after vaccination. The litters borne were normal. Prostate showed recovery after 154 days of vaccination. Our observations lend strong support to the hypothesis that anti-LHRH vaccine can be effectively used on the management of prostate carcinoma. If the vaccination is given together with a suitable dose of long-acting androgen, contained in an adequate delivery system, the regimen may be used for the regulation of male fertility.

Bioassay for determination of human serum luteinizing hormone (LH): a routine clinical method.

Serum levels of LH are used as marker of a number of pathological conditions. In the past many methods (RIA, IRMA, ELISA) have been employed to measure serum LH, these procedures, however, suffer from the drawback that they determine the immuno reactive and not the bioactive part of the hormone. An improved in vitro bioassay method for the estimation of serum LH has been described. The underlying mechanism of the assay is testosterone production by mouse Leydig cells in the presence of added LH. The method has been significantly improved in terms of sensitivity (0.2 IU/l) and simplicity; the assay is simple and does not require any special instruments and can be set up in any endocrinological laboratory.

The effect of gossypol acetic acid on the different stages of the spermatogenic cycle in the rat.

The reversibility of the effect of gossypol on testicular histology and fertility was studied in rats. Adult males of proven fertility were treated orally with gossypol acetic acid (15 mg/kg) for 9 or 16 weeks (groups 1 and 2, respectively). Another groups of animals (group 3) was given gossypol (15 mg/kg) for 16 weeks and killed 6 weeks after the end of treatment. Control animals (group 4) were given the vehicle only by oral intubation. In the mating studies, although only 33% of the animals in group 1 were infertile, 100% infertility was observed following 16 weeks of gossypol treatment (group 2). All animals in group 3 regained their fertility 6 weeks after cessation of drug treatment. Damage was observed to 15.7% of the seminiferous tubules after 9 weeks of drug treatment, and to 78% after 16 weeks of treatment. Extensive vacuolization, increased numbers of lipid droplets, degeneration of germ cells, loosening of the epithelium, and a significant decrease in the number of pachytene spermatocytes (stages VII-X) and spermatids (steps 7-10 at stages VII-X) were observed after gossypol treatment. There was a decrease in the diameter of only stage VIII seminiferous tubules after 9 weeks of treatment, whereas a reduction was observed in the tubules of all stages after 16 weeks of gossypol treatment. In the recovery phase, the diameter of seminiferous tubules was similar to that of controls, except for tubules at stage VIII. No change in the area of the lumen of the seminiferous tubules and lipid bodies was observed after 9 weeks of drug treatment, but a marked reduction in the area of the lumen (stages II-X) and an increase in lipid bodies (all stages) was observed after 16 weeks of gossypol treatment. Six weeks after cessation of treatment, the area of the lumen and the number of lipid bodies were comparable to values in controls. A reduction in the area of the epithelium was restricted to just a few stages (VIII-XIV) in treated animals at 9 weeks, whereas after 16 weeks the area of the epithelium was decreased in all tubules. In the recovery phase, except for tubules at stage VIII, the area of the seminiferous epithelium was comparable to that in controls.

Involvement of prostaglandin in the antifertility effects of gossypol.

This study was undertaken to determine the effects of gossypol alone and gossypol in combination with prostaglandin and aspirin. Rats were administered gossypol (40 mg/kg/day), gossypol and prostaglandin (PGF2 alpha-2 mg/kg/day), gossypol and aspirin (300 mg/kg) for 4 weeks. A marked effect of the gossypol-prostaglandin combination was observed on sperm motility and spermatogenesis. The effect of the gossypol-aspirin combination was less pronounced. The ratio of body weight to testicular and epididymal weights between the different groups showed no marked difference. No effect of drug treatment on plasma testosterone, LH and FSH was observed. The data presented in this paper suggest that prostaglandin plays an important role in the antifertility effects of gossypol.

Ultrastructure of monkey (Macaca radiata) spermatozoa: effect of gossypol in vivo.

The present study examines the ultrastructure of ejaculated spermatoza from bonnet monkey, Macaca radiata under normal conditions, with gossypol treatment and during recovery from such treatment. Monkeys were fed orally with gossypol acetic acid (GAA) for 3 months (4 mg/monkey/5 days a week). Semen samples collected by electro-ejaculation, and the spermatozoa were examined using both light and electron microscopy. The degree of motility was also noted by Kalla et al. Ejaculated spermatoza were immotile 90 days after GAA treatment, but little evidence for any abnormality in the spermatozoa could be seen by light microscopy. Some ultrastructural changes were observed, but not to the extent previously reported in spermatozoa of Macaca fascicularis. After termination of treatment, semen samples were obtained every 5th day until sperm count and motility recovered to the normal level. After 90 days only a small proportion of spermatozoa showed abnormal structure. We conclude that in a subhuman animal model gossypol induced effects on sperm motility and morphology are reversible.

Effect of gossypol on immature male rats.

In immature male rats the body growth rate, the testis and epididymis weight were not affected by gossypol treatment (4, 8 and 40 mg/kg body weight/24 hrs. for 30 days). There was however a marked reduction in the weight of the prostate after high dose gossypol administration. Furthermore gossypol treatment did not show any effect on the histoarchitecture of the testis nor did the drug treatment have any effect on sperm motility. The plasma levels of testosterone, LH and FSH in gossypol treated animals were no different from those on the controls.

In vivo study of LDH isoenzyme activities in heart, liver and testis cytosols of gossypol-treated rats.

LDH isoenzyme activities of heart, liver and testis homogenates were measured in rats treated for 15 or 30 days with 30 mg gossypol acetic acid/kg body weight daily, a dose which severely suppressed sperm motility. No differences in LDH activities of the examined organs were found in comparison with control animals. LDH-X, the main LDH isoenzyme in spermatozoa and testicular germ cells from primary spermatocytes onwards was also unaffected. These results contrast with in vitro experiments on human, rabbit, and boar spermatozoa, purified bovine LDH-X and rat testis homogenate which show dose-dependent inhibition of LDH-X after incubation with gossypol. Our results therefore suggest that inhibition of LDH by gossypol is not the primary cause of sperm immotility.

Effect of gossypol on bull spermatozoa in vitro.

Gossypol acetic acid in a concentration of 1,000 microgram/ml solvent is able to immobilize 1 ml of native bull semen (sperm concentration: 8.5 X 10(8)/ml; motility rate: 87.4%) within 30 min. After GAA treatment the spermatozoa show severe morphological damage on the membrane system, on the acrosomal complex and on the tubular complex of the end piece. The working mechanism of GAA can be assumed to be inactivation of enzyme activities or in direct reactions with plasma membrane material.

Effect of gossypol on testicular testosterone production in vitro.

Testicular minces were utilized to study the effect of gossypol on testosterone production. Testosterone production was assessed in both control nd gossypol treated groups after 0 to 4 hours incubation in the presence of hCG. Media testosterone was measured by radioimmunoassay. Gossypol did not alter testosterone production when present in incubates at the concentrations of 3.5 x 10(-5) M, 7 x 10(-5) M and 3.5 x 10(-4) M. Preincubation of testis mince with gossypol (7 x 10(-6) M, 7 x 10(-5) M, 3.5 x 10(-4) M) for 1 to 4 hours did not alter subsequent hCG induced testosterone production in mature rats. Testosterone production however, was inhibited in immature rat testis when the whole testis was incubated for 4 hours with different concentrations of gossypol (7 x 10(-6) M, 7 x 10(-5) M, 3.5 x 10(-4) M). In vivo testosterone production was not inhibited in the immature rat testis 24 hours after oral administration of gossypol (100 mg/kg).

Toxicity of gossypol at antifertility dosages in male rats: statistical analysis of lethal rates and body weight responses.

The lethal rates and body weight responses of male Wistar rats following oral treatment with gossypol acetic acid (GAA) at dosages of 2.5-30 mg/kg were analysed by various statistical procedures. Daily treatment with GAA for 10 weeks was associated with lethal rates significantly different from placebo groups in both the low dose (2.5, 5.0, and 7.5 mg/kg, p less than 0.05) and high dose groups (15, 20 and 30 mg/kg, p less than 0.01). The pronounced mean body weight gain observed in placebo groups, was suppressed in the GAA-treated groups at each dose level after 10 weeks. This indicates decreased appetite and/or lessened feed utilisation caused by GAA activity. GAA administration at a dose of 30 mg/kg every other day exerted identical deleterious effects as daily treatment. As derived from the antifertility responses of the GAA treatment groups it was evident that the toxic activity of GAA was not related to its antifertility efficacy. It is concluded that GAA has remarkable toxicity at antifertility dosages in rats.

The endocrine status of gossypol - treated male rats.

Male adult Wistar rats were exposed daily or every other day to oral gossypol acetic acid (GAA) concentrations of 2.5-30 mg/kg for 10-20 weeks. Controls received the GAA-suspension medium or were left completely untreated. The serum concentrations of testosterone, LH and FSH as well as the weight of testis, epididymis, prostate, seminal vesicle, coagulating gland, and pituitary were determined. The accessory sex organs were prepared for light microscopy. Significant antifertility effect in these animals was achieved at GAA-dosage of 15 mg/kg and higher. GAA-administration neither altered the serum hormonal profiles nor the reproductive organ weights in comparison to the controls. Accordingly, light microscopical examination revealed no alterations in the histological picture of prostate, seminal vesicle and coagulating gland when compared with the controls. The results indicate that GAA does not interfere with the hypothalamic-pituitary-gonadal axis in male adult rats.

Effect of intratesticular administration of BCG on testicular function (preliminary report).

Four patients suffering from carcinoma of the prostate (2 in stage C and 2 in stage D) in whom orchidectomy was indicated clinically, were enrolled in the study. Two patients were given a single injection of 25 units of BCG per testis and the other two received 50 units intratesticularly. Testicular biopsy at 0, 4 and 16 weeks showed the effects of the procedure in the tubular and interstitial compartment. The tubules were partially or completely atrophied, Sertoli cells were vacuolated. In the interstitium, mononuclear infiltration was evident. The reaction was more intense in patients receiving 50 units. The plasma testosterone after a slight drop in the first month returned to normal and pretreatment levels, respectively, and remained so during the eight months of observation. There was no significant change either in plasma oestradiol and prolactin or in T3, T1 and cortisol levels. FSH and LH, however, increased beyond the basal levels after an initial drop. The general condition of the patients remained good. All four patients gained weight. No side effects other than scrotal swelling during the first few weeks were either seen or reported by the patients. The swelling subsided after four weeks. This preliminary study indicates that there is a partial or total destruction of geminal elements. As the plasma testosterone levels remained undiminished in these four cases over a period of 8 months, it is apparent that testosterone production is not affected by intratesticularly administered BCG.

Ultrastructural analysis of rat testes after gossypol acetic acid (GAA) treatment.

The present investigations were carried out to show the histological and ultrastructural alterations in rat testes 10 weeks after gossypol acetic acid treatment (dose: 30 mg gossypol acetic acid/kg/day). the morphological findings in the interstitial compartment were compared with the data from studies carried out to investigate the testosterone biosynthesis in gossypol acetic acid treated rats. No morphological changes in the epididymal and vasal epithelia were found; however, the germinal epithelial cells showed vacuolisation, pycnosis, disconnections of junctions, cytolysis and exfoliation of germ cells from the epithelium. The Sertoli cells were affected, too. Gossypol acetic acid seemed to stimulate the physiological activity pathologically; cellular organelles as mitochondria, endoplasmic reticulum, lysosomal vacuoles, pigment granules and nuclei were either enlarged in size and number or malformed in shape. The cellular contact was often restricted to spots or completely disconnected. If gossypol acetic acid was administered for a longer period of time some Sertoli cells were found to be unable to withstand the toxic stimulus, and the cells became necrotic too. In contrast to the toxic process in the germinal and Sertoli cells the Leydig cell compartment did not show any changes in fine structure, and therefore testosterone biosynthesis is presumed to be intact.