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Biomedical subjects

E D Kim

Publications and source records attributed to E D Kim.

At least 19 recordsLinked to original sources

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.

Adult↗

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.

Blood Loss, Surgical↗

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.

Case-Control Studies↗

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.

Aged↗

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.

Cystic Fibrosis Transmembrane Conductance Regulato↗

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.

Adult↗

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.

Diagnostic Imaging↗

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.

Follow-Up Studies↗

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.

Amino Acid Sequence↗

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.

Adult↗

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.

Adult↗

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.

Adult↗

Germ-cell nondisjunction in testes biopsies of men with idiopathic infertility.

Intracytoplasmic sperm injection (ICSI) has been used in combination with testicular sperm extraction to achieve pregnancies in couples with severe male-factor infertility, yet many of the underlying genetic mechanisms remain largely unknown. To investigate nondisjunction in mitotic and meiotic germ cells, we performed three-color FISH to detect numeric chromosome aberrations in testicular tissue samples from infertile men confirmed to have impaired spermatogenesis of unknown cause. FISH was employed to determine the rate of sex-chromosome aneuploidy in germ cells. Nuclei were distinguished as haploid or diploid, respectively. The overall incidence of sex-chromosome aneuploidy in germ cells was found to be significantly higher (P<.00001) in all three abnormal histopathologic patterns (range 39.0%-43.5%) as compared with normal controls (29.1%). The relative ratio of normal to aneuploid nuclei in the diploid cells of patients with impaired spermatogenesis was approximately 1.0, a >300% decrease when compared with the 4.42 ratio detected in patients with normal spermatogenesis. These results provide direct evidence of an increased incidence of sex-chromosome aneuploidy observed in germ cells of men with severely impaired spermatogenesis who might be candidates for ICSI with sperm obtained directly from the testis. The incidence of aneuploidy was significantly greater among the diploid nuclei, which suggests that chromosome instability is a result of altered genetic control during mitotic cell division and proliferation during spermatogenesis.

Biopsy↗

Varicocele repair improves semen parameters in azoospermic men with spermatogenic failure.

PURPOSE: We analyzed the efficacy of varicocele repair in improving semen parameters in azoospermic men with spermatogenic failure. MATERIALS AND METHODS: After routine clinical evaluation with confirmatory pellet analysis testicular biopsy and varicocele repair were simultaneously performed in 28 azoospermic men with a primary diagnosis of unilateral or bilateral varicocele and spermatogenic failure. Semen analyses were obtained starting 4 months after varicocelectomy. RESULTS: Repair was bilateral repair in 20 men and unilateral in 8. Of the 28 men 12 (43%) had sperm in the ejaculate with a mean postoperative sperm count plus or minus standard deviation of 1.2+/-3.6x10(6)/ml. and an average followup of 24 months. Mean sperm motility was 19+/-24% (range 0 to 80). Testicular biopsy was predictive of outcome. Only 9 men with severe hypospermatogenesis and 5 with maturation arrest spermatid stage had improvement in sperm density. No improvement was seen in 3 men with the Sertoli-cell-only pattern or 3 with maturation arrest spermatocyte stage. No pregnancies by natural intercourse resulted. One couple used fresh ejaculate for intracytoplasmic sperm injection and 1 underwent testicular sperm extraction with intracytoplasmic sperm injection. Both pregnancies resulted in live births. No other predictive factors were identified. CONCLUSIONS: Varicocele repair can result in sperm in the ejaculate of azoospermic men when severe hypospermatogenesis or maturation arrest spermatid stage is present. Select men with spermatogenic failure and varicoceles may be candidates for varicocele repair, rather than resorting to testis biopsy for sperm extraction in preparation for intracytoplasmic sperm injection. However, the couple should be counseled that assisted reproductive technologies will most likely be required to initiate pregnancy.

Adult↗