Perfusion index as a reliable parameter of vasomotor disturbance in complex regional pain syndrome.

BACKGROUND: Discrepancy between a patient's subjective thermal symptoms and objective measured temperature value is common in complex regional pain syndrome (CRPS) in clinical settings. For that reason, the diagnostic validity of a single temperature measurement method has been criticised. Several studies showed that the perfusion index (PI), which is derived from pulse oximetry, is a more sensitive and earlier indicator of sympathetic blockade than temperature measurement. METHODS: Forty-six participants (CRPS group, n=23; healthy control group, n=23) were enrolled. CRPS patients with subjective sensation of coldness on the affected side were chosen for this study. Temperature and PI were measured at the affected and contralateral hands in the CRPS group, and right and left hands in the healthy control group. To evaluate each method's efficacy for detecting thermal symptoms, differences in the parameters (temperature: ΔT, PI: ΔPI) were compared with receiver operating characteristic curves. RESULTS: ΔPI was significantly larger in the CRPS compared with the healthy control group (P=0.002), but ΔT was not (P=0.171). The accuracy of PI measurement for reflecting thermal symptoms was good (area under the curve for ΔPI: 0.873, P<0.0001). The optimal cut off value of ΔPI was calculated as 0.50% with a sensitivity of 78.26%, whereas the sensitivity of ΔT using the conventional criterion of ≥1°C was only 34.78%. CONCLUSIONS: The accuracy of detection of subjective abnormal thermal sensations was superior for PI compared with the temperature measurement method. PI was a more sensitive measure for detecting vasomotor symptoms in CRPS compared with temperature.

Designer steroids - over-the-counter supplements and their androgenic component: review of an increasing problem.

Colloquially referred to by various misleading monikers ('pro-hormones', 'natural steroids', 'testosterone boosters', etc.) designer anabolic steroids have been popular now for over a decade as a way to achieve classic anabolic steroid-like results from products sold in the legal marketplace. Recent evidence suggests that anabolic steroid use may be the most common cause of hypogonadism in men of reproductive age. Despite recent regulatory efforts that have banned specific compounds, many anabolic-androgenic steroids (AAS) remain available in over-the-counter dietary supplements that are legally sold in the United States. Severe side effects including hepatotoxicity, cholestasis, renal failure, hypogonadism, gynecomastia, and infertility have been reported secondary to the use of these products. While some of these side effects may be reversible, more aggressive use may result in more permanent end-organ damage as has been previously described for the case of aggressive AAS users (Rahnema et al., Fertil Steril, 2014). Designer AAS remain easily available for purchase in over-the-counter bodybuilding supplements and these products appear to be increasingly popular, despite the known health risks associated with their use. We conducted a systematic search to identify the designer steroids that are most commonly sold in dietary supplements as of April 2014 and review what is known regarding their potency and toxicity. We propose that the impact of AAS use on the reproductive and hormonal health of men is underestimated in the literature owing to previous studies' failure to account for designer steroid use. Lastly, we make clinical recommendations to help physicians steer patients away from potentially harmful supplements, and summarize key regulatory obstacles that have allowed potent androgens to remain unregulated in the legal marketplace.

Uric acid and the risk of graft failure in kidney transplant recipients: a re-assessment.

The association of hyperuricemia with kidney allograft outcomes remains controversial. We studied this problem in 1170 kidney transplants from January 2000 to December 2010. The primary endpoint was total graft failure (i.e. graft loss or death). Conventional, time-dependent and marginal structural Cox proportional hazards models were fitted, the latter accounting for kidney function as a time-varying confounder affected by prior uric acid levels. Uric acid level was associated with an increased risk of total graft failure in time-fixed and time-varying models (HR 1.02 [95% CI: 1.003-1.04] and HR 1.02 [95% CI: 1.01-1.03], respectively, for every 10 µmol/L increase in uric acid). In contrast, the marginal structural model showed a modestly protective effect (HR 0.90 [95% CI: 0.85-0.94] for every 10 µmol/L increase in uric acid). Similar results were observed for death-censored graft failure and death with graft function. In summary, the absence of a deleterious association between elevated uric acid and graft outcome after accounting for graft function as a time-varying confounder suggests that uric acid is not an independent risk factor for graft failure. The modestly protective effect of uric acid may be an indicator of nutritional status but further study is warranted.

Retrospective analysis of the efficacy and safety of once-daily tadalafil in patient subgroups: men with mild vs moderate ED and aged <50 vs 50 years.

The aim of this post-hoc pooled-data analysis was to evaluate the effects of once-daily tadalafil in men with mild or moderate ED and aged <50 or 50 years. Data from three randomized controlled trials were analyzed. Analysis of covariance models included a term for ED severity and age group. The three coprimary outcome measures in the base studies were changes from baseline to end point in the mean International Index of Erectile Function Erectile Function (IIEF-EF) domain score and the mean per-patient percentage successful vaginal penetration and intercourse attempts. Irrespective of baseline severity, once-daily tadalafil 5 mg for 12 weeks compared with placebo significantly increased the mean: (1) IIEF-EF by 6.8; (2) percent successful penetration attempts from 70.1 to 91.3%; and (3) percent successful intercourse attempts from 33.4 to 76.8% (each P<0.001). Treatment-by-age-group interaction P-values for all three coprimary efficacy end points exceeded 0.10, indicating that tadalafil treatment effects did not differ by age <50 vs 50 years. Tadalafil was generally well tolerated.

Response to treatment with tadalafil in men with erectile dysfunction who reported no successful intercourse attempts at baseline.

The purpose of this post hoc analysis was to evaluate response to tadalafil in patients with erectile dysfunction (ED) who reported failures in all sexual intercourse attempts before treatment. In a multicenter, open-label study, 1911 men received tadalafil 20 mg dosed as needed (up to once daily), for 12 weeks following a 4-week treatment-free run-in period. Efficacy measures included the sexual encounter profile (SEP) and the erectile function (EF) domain of the International Index of Erectile Function (IIEF-EF). Approximately, one-half (n=952, 49.9%) of the patients reported no successful intercourse attempts during the 4-week run-in period. Of these, 771 patients (81.0%) had at least one successful intercourse attempt during the treatment period. Furthermore, among responders, mean IIEF-EF scores at study end were similar regardless of success or no success at baseline. Patients who are unable to have successful intercourse should be encouraged to try oral phosphodiesterase type 5 inhibitor treatment for ED.

Efficacy and safety of vardenafil in men with erectile dysfunction caused by spinal cord injury.

OBJECTIVE: To assess the efficacy and tolerability of vardenafil in men with erectile dysfunction (ED) due to traumatic spinal cord injury (SCI). METHODS: In this multicenter, double-blind, placebo-controlled, parallel-group 12-week study, 418 men aged 18 years and older with ED for more than 6 months consequent to SCI were randomized to vardenafil (n = 207) or placebo (n = 211) (10 mg for 4 weeks, then maintained or titrated to 5 or 20 mg at weeks 4 and 8). Efficacy assessments included the erectile function (EF) domain score of the International Index of Erectile Function questionnaire and diary questions regarding penetration, maintenance of erection to completion of intercourse, and ejaculation. RESULTS: Baseline patient characteristics were similar in the vardenafil (mean age 40 years) and placebo (mean age 39 years) groups. Mean baseline EF domain scores were 11.6 in the vardenafil group and 12.1 (moderate ED) in the placebo group. EF domain score in the vardenafil group improved to 22.0 (mild ED) at last observation carried forward vs 13.5 in the placebo group (p < 0.001). Over 12 weeks of treatment, mean per-patient penetration (76% vs 41%), maintenance (59% vs 22%), and ejaculation (19% vs 10%) success rates were significantly greater vs placebo (all p < 0.001). The most frequently reported drug-related adverse events were headache (vardenafil 15%, placebo 4%), flushing (vardenafil 6%, placebo 0%), nasal congestion (vardenafil 5%, placebo 0%), and dyspepsia (vardenafil 4%, placebo 0%). CONCLUSION: Vardenafil significantly improved erectile and ejaculatory function and was generally well tolerated in men with erectile dysfunction due to spinal cord injury.

Bilateral nerve grafting during radical retropubic prostatectomy: extended follow-up.

OBJECTIVES: To confirm the benefit of using an interposition sural nerve graft at the time of radical retropubic prostatectomy in an extended series of men with at least 1 year of follow-up. We previously reported the return of erectile function after resection of both cavernous nerves. METHODS: Twenty-eight potent men with clinically localized prostate cancer underwent radical retropubic prostatectomy with deliberate wide bilateral neurovascular bundle resection and the placement of bilateral nerve grafts. Erectile dysfunction questionnaires and patient interviews were completed at 6-month intervals. A minimum of 12 months of follow-up (mean 23 +/- 10 months) was obtained for 23 men (mean age 58 +/- 6 years). A control group of 12 men who underwent bilateral nerve resections, but declined nerve graft placement, was also followed up. RESULTS: Of the 23 men, 6 (26%) had spontaneous, medically unassisted erections sufficient for sexual intercourse with vaginal penetration. An additional 6 men (26%) described "40% to 60%" spontaneous erections (fullness, no rigidity, not able to penetrate). Ten men (43%) had intercourse with sildenafil. No demonstrable erections occurred before 5 months postoperatively. The greatest return of function thus far was observed at 18 months after surgery. CONCLUSIONS: This surgical technique continues to show promise as an advance in prostate cancer surgery. The results of this study demonstrated recovery of erectile function in men who underwent bilateral nerve graft placement during radical retropubic prostatectomy when both cavernous nerves were deliberately resected.

Minimally invasive technique for sural nerve harvesting: technical description and follow-up.

OBJECTIVES: To provide instruction and the results of a minimally invasive technique for sural nerve harvesting in preparation for interposition nerve grafting during radical retropubic prostatectomy. METHODS: Twelve men underwent nerve harvesting performed using a tendon stripper. The short-form McGill Pain Questionnaire was completed preoperatively and at 6 months postoperatively. RESULTS: No significant morbidity from the leg resulted as a result of the sural nerve harvest. The results of the short-form McGill Pain Questionnaire demonstrated no significant sensory or affective changes in the leg. The average operative time for the entire harvesting procedure, including skin closure, was 15 minutes. The estimated blood loss was less than 5 mL (range 2 to 10). No wound infection or skin erythema was observed. The discharge to home was not delayed compared with the usual length of stay after radical retropubic prostatectomy. CONCLUSIONS: This minimally invasive sural nerve harvesting technique is easy to perform and has minimal morbidity.

An overview of male infertility in the era of intracytoplasmic sperm injection.

As a result of the technological advance provided by intracytoplasmic sperm injection (ICSI) in 1992, the evaluation and treatment of the infertile male has changed significantly. Many men who were previously thought to be irreversibly infertile have the potential to initiate their own biologic pregnancy. However, not all men having impaired semen parameters are ideal candidates for ICSI for numerous reasons including a lack of addressing the underlying problem causing the male infertility, unknown genetic consequences, and cost-effectiveness issues. In this era of ICSI, the fundamental approach to the male with suspected subfertility is unchanged and is based on a history, physical examination, and focused laboratory testing. The urologist should approach the patient with an intent to identify remediable causes of subfertility given the specific clinical situation. For instance, should a gentleman have his varicocele repaired or vasectomy reversed, or should he proceed directly with ICSI? If no factors can be improved in a timely manner, then ICSI should be considered using the available sperm. Examples of recent advances include the diagnosis and treatment of ejaculatory duct obstruction, indications and techniques for performing testis biopsy, and techniques for sperm harvesting. Potential genetic causes should be diagnosed and discussed with the patient. Cystic fibrosis gene mutations, karyotype abnormalities, and Y-chromosome microdeletions all have recently been identified as causative for male infertility in otherwise phenotypically normal men. While the long-term genetic consequences for these offspring are largely undefined, recent studies suggest that serious birth defects are not significantly increased in ICSI babies. An understanding of these advances by all physicians is important as we progress into the 21st century.

Bilateral nerve graft during radical retropubic prostatectomy: 1-year followup.

PURPOSE: With the interposition of a sural nerve graft to replace resected cavernous nerves at radical retropubic prostatectomy, we have previously reported the return of effective erectile function. We determine the efficacy of this procedure in a series of men with at least 1-year followup. MATERIALS AND METHODS: A total of 12 potent men (mean age plus or minus standard deviation 57 +/- 6 years) with clinically localized prostate cancer underwent radical retropubic prostatectomy, with deliberate wide bilateral neurovascular bundle resection and placement of bilateral nerve grafts. A series of patient and partner erectile dysfunction questionnaires, and patient interviews were performed at 3, 6, 12 and 18 months postoperatively. Only results for those men with a followup of 12 months or greater (mean 16 +/- 4) are presented. A control group of 12 men who had undergone bilateral nerve resection but declined nerve graft placement, was also followed. RESULTS: Of the 12 men 4 (33%) had spontaneous medically unassisted erections sufficient for sexual intercourse with vaginal penetration. An additional 5 (42%) men describe "40 to 60%" spontaneous erections, with fullness, no rigidity and not able to penetrate. Overall, 9 (75%) men had return of erectile activity. No demonstrable erections occurred before 5 months postoperatively. The greatest return of function was observed at 14 to 18 months after surgery. CONCLUSIONS: This surgical technique has minimal morbidity and represents a significant advance in prostate cancer surgery in men requiring bilateral nerve resection. Our study clearly demonstrates recovery of erectile function in men who underwent bilateral nerve graft placement during radical retropubic prostatectomy when both cavernous nerves were deliberately resected.

Side-effect profile of sildenafil citrate (Viagra) in clinical practice.

OBJECTIVES: Sildenafil citrate (Viagra) has been shown to be an effective treatment for erectile dysfunction. Initial studies reported a high tolerability and low incidence of certain characteristic adverse reactions. We sought to evaluate the incidence of side effects of sildenafil citrate, independent of industry support and constraints, utilizing a heterogeneous cohort of patients from a university-based practice. METHODS: A prospective, open-label, flexible-dose study of 256 patients treated with sildenafil citrate for erectile dysfunction was performed at a single institution. The patients were questioned explicitly about the occurrence of headache, flushing, dyspepsia, nasal congestion, visual changes, and other side effects. RESULTS: The adverse reactions most commonly observed were flushing (30.8%), headache (25. 4%), nasal congestion (18.7%), and heartburn (10.5%). All events were short lived and mild in nature. In the present study, 31.6% of patients experienced one or more adverse events. However, no one withdrew from the study because of the severity of these events. There was a significant association between higher doses and the occurrence of side effects. CONCLUSIONS: The incidence of adverse events attributable to sildenafil citrate may be higher than initially reported, but an explanation may be the methodology of data collection and the industry-independent nature of this study. The side-effect profile is dose related and mild. Sildenafil citrate remains a safe and well-tolerated treatment for erectile dysfunction.

Contemporary approach to the male infertility evaluation.

Evaluation of infertile couples has revealed that male factor infertility contributes to the problem in up to 50% of cases. Evaluation of the male infertility patient may include endocrine studies, sophisticated semen testing, and select radiographic studies. Reversible and life-threatening causes of male infertility should be identified before proceeding directly to assisted reproductive technology. For cases with irreversible causes, a proper evaluation can identify patients who may be treated with the breakthrough method of intracytoplasmic sperm injection. Many men who were previously thought to be infertile may now initiate their own biologic pregnancies. This article emphasizes the essentials of the contemporary approach to evaluating the male factor in an infertile couple.

Molecular cloning and characterization of functional domains of a human testis-specific isoform of calpastatin.

Human serum containing sperm-agglutinating antibodies was used to screen a testis cDNA expression library to identify the cognate antigens that may be responsible for this biological effect. The longest positive phage clone (1.9 kb) was sequenced and found to be a testis-specific isoform of calpastatin (tCAST). The testis-specific segment of tCAST is encoded by a single exon within intron 14 of the calpastatin gene. A unique protein isoform is produced that differs in domain structure from the somatic calpastatins (sCAST). Human sCAST most commonly has an N-terminal domain L plus the four functional calpain inhibitory domains. Human tCAST consists of a 40-amino-acid N-terminal T domain plus a part of domain II and all of domains III and IV from the somatic isoform. Our data show that the T domain can target cytosolic localization and membrane association of tCAST, whereas domain I of sCAST exhibits a nuclear localization function. Calpastatin is the endogenous inhibitor of calpain. The calpain/calpastatin system is involved in membrane fusion events for several cell types, and calpain has been localized to the sperm acrosome. We detected tCAST in human sperm and testes extracts by Western blotting with specific antisera. These observations suggest that tCAST may modulate calpain in the calcium-mediated acrosome reaction that is required for fertilization.

Treatment of infertility due to anejaculation in the male with electroejaculation and intracytoplasmic sperm injection.

PURPOSE: We tested the hypothesis that spinal cord injury and/or anejaculation affects the outcome of intracytoplasmic sperm injection (ICSI). MATERIALS AND METHODS: From November 1993 to October 1998 we obtained and prospectively reviewed data on 34 ICSI cycles using electroejaculated sperm, 620 male factor infertility ICSI cycles using normal ejaculated sperm and 120 cases of obstructive azoospermia, in which microsurgical epididymal aspiration and testicular sperm extraction-ICSI were done in 93 and 27, respectively. RESULTS: A total of 34 ICSI cycles were performed in 17 couples with male infertility due to anejaculation secondary to spinal cord injury in 10 patients and retroperitoneal lymph node dissection in 5, and idiopathic in 2. In all 17 couples at least 3 previous intrauterine insemination cycles had failed. After electroejaculation 11 men had oligozoospermia and 6 normal sperm density. Median sperm retrieval volume plus or minus standard deviation was 1.9 +/- 1.9 ml., median sperm concentration 70.7 +/- 60.2 x 106 sperm per ml., median motility 10.7% +/- 10.8% and median forward progression 2.3 +/- 0.5 (scale 1 to 4). In the anejaculation group ICSI resulted in a median fertilization of 60% +/- 28%, 15% pregnancies per cycle and 29% pregnancies per couple. In the control group of 620 ICSI cycles from ejaculated specimens obtained from male patients with infertility median fertilization was 58% +/- 26%, and there were 39% pregnancies per cycle and 47% pregnancies per couple. The rate of pregnancies per embryo transfer and per couple was higher in the control than in the electroejaculation-ICSI group (p <0.05). However, there was no statistically significant difference in the fertilization rate. CONCLUSIONS: ICSI or in vitro fertilization is a viable alternative for patients with anejaculation in whom intrauterine insemination failed. While the fertilization rate is similar in these couples, the pregnancy rate is significantly lower than that achieved with ejaculated specimens from patients with severe male factor infertility. ICSI is a viable alternative for a patient with anejaculation in whom intrauterine insemination or in vitro fertilization failed.

Testis biopsy findings in the spinal cord injured patient.

PURPOSE: Azoospermia after electroejaculation in spinal cord injured men may be due to testicular failure or obstruction. These men can initiate pregnancy with assisted reproductive techniques, such as intracytoplasmic sperm injection, but only if sperm are present in the testis biopsy. We analyzed the histopathology of testis biopsies from spinal cord injured men and assessed whether patient factors were predictive of testis biopsy pathology. MATERIALS AND METHODS: A total of 50 paraplegic men undergoing testis biopsy were divided into 2 groups based on normal or abnormal testis histopathology. Patient age, post-injury years, level of lesion, hormonal status and semen analysis results were compared. RESULTS: Spermatogenesis was normal in 28 of the 50 patients. Hypospermatogenesis was exhibited in 15, maturation arrest at the spermatid stage in 6 and maturation arrest at the spermatocyte stage in 1 of the 22 abnormal cases. Nevertheless, mature sperm were identified in 43 of 50 biopsies (normal spermatogenesis and hypospermatogenesis). Men with normal spermatogenesis had better forward progression of sperm and a higher testosterone-to-luteinizing hormone ratio. Otherwise, there was no statistically significant correlation between study variables and testis biopsy results. No factors were predictive of testis biopsy histopathology. CONCLUSIONS: The documentation of mature sperm in 43 of 50 biopsies from spinal cord injured patients suggests that a high rate of sperm retrieval is possible using testicular sperm extraction if sperm cannot be retrieved from the ejaculate. With intracytoplasmic sperm injection techniques the majority of spinal cord injured men retain fertility potential, even if azoospermic following electroejaculation.

Penile fibrotic changes after radical retropubic prostatectomy.

OBJECTIVE: To investigate the type of penile deformity, response to treatment of and predictive factors for the formation of penile fibrotic changes after radical retropubic prostatectomy (RRP). PATIENTS AND METHODS: Between July 1996 and September 1998, 110 men who had undergone RRP a mean (SD, range) of 35 (20, 5-145) months previously were evaluated by one physician for their erectile dysfunction. Those men affected by penile fibrotic changes were advised to initiate medical therapy for possible Peyronie's disease; their charts were reviewed and they were interviewed to determine the outcome. RESULTS: Overall, 45 of 110 patients (41%) with erectile dysfunction after RRP had penile fibrotic changes, representing 11% of all patients undergoing RRP in the specified period. The primary clinical presentation included penile curvature in 42 men (93%) and 'waistband' deformity in 11 (24%; some had both); palpable plaques were present in 31 (69%). On assessing the outcome in 40 men, 16 (40%) felt that their condition had improved, half were unchanged and 10% progressed, within a mean follow-up of 24 months after diagnosis. Of the 16 improved, 14 were regularly using a vacuum constriction device or injection therapy. No significant factors predictive of the fibrotic changes could be identified, including the use of intracavernosal injection therapy before onset, neurovascular bundle resection, operative duration, estimated blood loss and pathological tumour grade or stage. CONCLUSIONS: Penile fibrotic changes are a significant but previously undescribed problem in men after RRP. Although predisposing factors could not be identified, most men felt that their condition stabilized or improved during treatment. Corroborative confirmation of this association and its aetiology will require prospective studies.

Sildenafil citrate after radical retropubic prostatectomy.

PURPOSE: Erectile dysfunction continues to be a significant problem for men after radical retropubic prostatectomy despite nerve sparing techniques. Sildenafil citrate (Viagra) has proved effective for erectile dysfunction in many men. We determine the efficacy of sildenafil in men with erectile dysfunction after radical retropubic prostatectomy and examine variables that may impact the response to treatment. MATERIALS AND METHODS: A total of 84 men were prescribed sildenafil after radical retropubic prostatectomy and asked to complete a series of questionnaires, including the International Index of Erectile Function (IIEF), on erectile function before and after sildenafil administration. The importance of factors, such as patient age, time since surgery, degree of cavernous nerve sparing, preoperative prostate specific antigen, Gleason score, clinical and pathological stage, and baseline postoperative erectile function, was examined. RESULTS: Of the 84 patients 45 (53%) had improved erections and 34 (40%) had improved ability for intercourse while taking sildenafil. Mean IIEF score for the erectile function domain increased from 9 to 14 (p <0.001). Orgasmic function (p = 0.004) and intercourse satisfaction (p = 0.009) also significantly improved. The degree of nerve sparing and baseline postoperative erectile dysfunction had a significant impact on the ability of sildenafil to improve erectile function (p = 0.010 and p <0.001, respectively) and total IIEF questionnaire responses (p = 0.031 and p <0.001, respectively). Age and pathological stage also appeared to have a significant effect. CONCLUSIONS: Sildenafil improved erectile function and the ability to have intercourse in more than half of men after radical retropubic prostatectomy. Baseline postoperative erectile function, which is dependent on the degree of nerve sparing technique, significantly impacts the likelihood that patients will respond to sildenafil.

The role of autosomal cell apoptosis regulator genes in human spermatogenesis.

Immunohistochemical analysis of the expression of the autosomal apoptosis regulator genes, BAX, bcl-2, p53, and cyclic-AMP responsive element modulator (CREM) in testis biopsies from infertile men demonstrated that BAX, bcl-2, and p53 immunoreactivity was absent irrespective of seminiferous tubule histology. In contrast, cell-specific CREM immunoreactivity in round spermatids, with complete absence of CREM in patient biopsies showing spermatocyte maturation arrest and Sertoli cell only, was evident, suggesting a possible role of autosomal genes in the regulation of apoptosis in human spermatogenesis regulation.