Treatment of erectile dysfunction in men with diabetes.
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Biomedical subjects
Publications and source records attributed to E D Kim.
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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.
PURPOSE: The permanent loss of erectile function when both neurovascular bundles are widely resected at radical prostatectomy as well as the successful use of autologous nerve grafts in reconstructive surgery led us to perform bilateral nerve grafts in an effort to restore erectile function in potent patients treated for prostate cancer who underwent radical retropubic prostatectomy and resection of both neurovascular bundles. MATERIALS AND METHODS: Radical retropubic prostatectomy with deliberate resection of both neurovascular bundles was recommended for high grade, locally extensive prostate cancer in 9 select, sexually active men who reported normal erectile function. After the prostate was removed but before vesicourethral anastomosis an autologous sural nerve graft was interposed between the divided ends of the cavernous nerves bilaterally. Erectile function was monitored by patient interview, questionnaire and nocturnal penile tumescence testing after the operation. RESULTS: Four to 5 months postoperatively patients noticed slowly improving spontaneous erections, as manifested by mild tumescence regularly every several hours. Nocturnal penile tumescence testing with the RigiScan device at 4 to 6 months in 2 cases revealed erections that approached minimal criteria for normalcy. Approximately 14 months after surgery a rigid erection sufficient for penetration and intercourse developed in 1 patient. He described this event as "an erection of substance-hard, not just fluffy." CONCLUSIONS: We have developed a technique using sural nerve grafts to restore continuity of the cavernous nerves, which are resected during radical prostatectomy. The early return of spontaneous partial erections in our patients suggests that interposition nerve grafts may enhance the recovery of erectile function when the neurovascular bundles are resected.
OBJECTIVE: To obtain evidence of metabolic changes in the human prostate associated with prostate pathology, in particular carcinoma of the prostate, by identifying and evaluating associated changes in prostatic secretory products. METHODS: Expressed prostatic fluid (EPF) from 36 patients with carcinoma, 128 with BPH histologically confirmed, and 148 with clinical BPH was subjected to determination of protein (Lowry; UV 280 nm absorption), enzymatic (DMA modified Row procedure) acid phosphatase (AcP), and immunologically identified (Tandem-PAP immunoenzymatic assay) prostatic acid phosphatase (PAP) concentration. RESULTS: The important EPF findings are the following: (1) Protein concentrations (Lowry and UV determinations) are significantly increased in carcinoma as compared to histologic BPH, (2) AcP and PAP secretions remain stable in carcinoma versus BPH, and (3) AcP and PAP/Lowry protein ratios are significantly lower with carcinoma. CONCLUSIONS: These findings of increased protein and the decreased relative secretions of AcP and PAP to total protein (ratio) in EPF from patients with carcinoma compared to BPH support and help to characterize the diffuse metabolic alteration in the prostate associated with prostate carcinoma. EPF observations identify potential metabolic changes occurring in prostate carcinoma that may have potential clinical and investigative relevance.
OBJECTIVE: To test the hypotheses that variations in the expression of adenosine 3':5' monophosphate (cAMP) responsive element modulator are found in human seminiferous epithelium in men with impaired testicular function and subsequent infertility and that variations in apoptosis frequency are associated with differential cAMP responsive element modulator expression in male infertility states. DESIGN: Standard immunohistochemical staining using a rabbit polyclonal antibody against the tau isoform of the cAMP responsive element modulator protein was performed on 5-microM sections of Bouin's fixed, paraffin-embedded testicular tissue obtained from azoospermic or severely oligozoospermic men for routine clinical purposes. Histologic diagnosis was confirmed with computerized image analysis of Feulgen-stained sections. SETTING: Tertiary male infertility referral center at a medical school. PATIENT(S): Forty-eight testis biopsies were performed in 38 azoospermic or severely oligozoospermic males. INTERVENTION(S): Rabbit polyclonal cAMP responsive element modulator tau antibody was applied to the paraffin-embedded testis sections. MAIN OUTCOME MEASURE(S): Testis immunoreactivity to polyclonal cAMP responsive element modulator tau antibody and apoptotic indices. RESULT(S): Although cAMP responsive element modulator immunoreactivity was present in the round spermatid stage of meiosis in testis biopsy specimens showing normal spermatogenesis, spermatid maturation arrest, and hypospermatogenesis, there was complete absence of expression in biopsy specimens from patients with Sertoli cell only and spermatocyte maturation arrest states. In addition, significantly increased apoptotic indices were observed in the spermatocyte maturation arrest state in comparison with normal spermatogenesis and Sertoli cell only pattern. CONCLUSION(S): These data suggest that cAMP responsive element modulator may be important for spermatid development and a stage-specific regulator of human spermatogenesis. Absence of cAMP responsive element modulator may be a cause of testicular failure in various types of male infertility.
PURPOSE: Because few studies have described the impact of unilateral testicular trauma on fertility parameters, we review the experience at the Ben Taub General Hospital during a 16-year period. Semen and endocrine profiles were analyzed to evaluate the influence on the outcomes of orchiectomy versus testicular salvage. MATERIALS AND METHODS: From 1979 to 1995, 67 patients were identified who sustained unilateral testicular trauma. Of these patients 12 were located and 10 agreed to be evaluated. Injuries included gunshot wounds, stab wounds and blunt trauma, and treatment consisted of unilateral orchiectomy or testicular repair. The study protocol comprised a history and physical examination, routine semen analysis, determination of semen and serum antisperm antibody titers (Immunobead* assay) and a modified gonadotropin stimulation test. Results were compared with a group of semen donors with proved fertility. RESULTS: In the 7 patients who underwent unilateral orchiectomy mean sperm density was normal but significantly decreased compared with that of the fertile controls (81.6 versus 132.6 x 10(6)/ml., p = 0.04). Sperm motility was not significantly affected. Baseline follicle-stimulating hormone (FSH) and luteinizing hormone (LH), and post-stimulation LH were significantly increased in this group compared with controls (p < 0.01). In the group that underwent testicular repair sperm density, motility, and baseline and post-stimulation FSH and LH levels were not significantly different from controls. In all patients in both groups testosterone levels and contralateral testicular size were normal. Only 1 patient in the repair group had an elevated serum and semen antisperm titer. CONCLUSIONS: While the testicular salvage group had no significant seminal or endocrine abnormality, the orchiectomy group had a significant decrease in sperm density and elevation of baseline FSH and LH. These preliminary data suggest that testicular salvage is more protective of overall testicular function than orchiectomy.
PURPOSE: In men considered to have azoospermia by routine semen analyses sperm may be identified after centrifuging the semen. Because these sperm may be used for intracytoplasmic sperm injection, we describe our technique and findings of sperm pelleting. MATERIALS AND METHODS: Semen centrifugation for sperm pellet analysis was performed in 140 consecutive men in whom no sperm was identified on routine semen analysis and who were categorized as having obstructive or nonobstructive azoospermia. Obstructive azoospermia was defined as failed vasectomy reversal, failed reconstruction for congenital vasal or epididymal occlusion, or an acquired obstruction unrelated to ejaculatory duct obstruction. Patients with congenital absence of the vas deferens or who had undergone vasectomy were not included in the study. Nonobstructive azoospermia was defined as moderate to severe testicular atrophy with markedly elevated serum follicle-stimulating hormone (greater than 3 times normal), or a testicular biopsy that revealed maturational arrest, severe hypospermatogenesis or the Sertoli-cell-only pattern. Obstructive and nonobstructive azoospermia were present in 70 men who provided 109 samples and 70 who provided 103, respectively. RESULTS: Motile and nonmotile sperm was identified in 13 of the 70 patients (18.6%) with obstructive and in 16 of the 70 (22.8%) with nonobstructive azoospermia. Pellet variability, that is the absence of sperm in 1 specimen and its presence in another from the same patient, was noted in 7 of the 17 men (41.2%) with obstructive and 2 of the 17 (11.8%) with nonobstructive azoospermia (not statistically significant). Motile sperm was present in the pellets of 6 of the 70 men (8.6%) with obstructive and 15 of the 70 (21.4%) with nonobstructive azoospermia. The median number of motile sperm was lower in the obstructive than in the nonobstructive group (0 sperm in 17 samples versus 5 sperm in 41 samples, p <0.001). The median value of 0 in the obstructive azoospermia group reflects the finding that 9 of the 17 samples did not contain motile sperm. Similarly the median number of nonmotile sperm was lower in the obstructive than in the nonobstructive group (5 versus 8 sperm). CONCLUSIONS: We demonstrated the presence of motile and nonmotile sperm in a significant number of men considered to have azoospermia by routine semen analysis. Semen centrifugation (sperm pelleting) should be performed in all men considered to have this condition by routine semen analysis, especially those with testicular failure and those in whom intracytoplasmic sperm injection is possible.
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PURPOSE: We determine the success of end-to-side epididymovasostomy in patients presenting with obstructive azoospermia from primary epididymal obstruction and identify prognostic factors that could predict a successful outcome. MATERIALS AND METHODS: Of 256 consecutive patients undergoing end-to-side epididymovasostomy 49 had primary epididymal obstruction unrelated to prior vasectomy. Patients were excluded from study if they had a history of vasectomy, microsurgical reconstruction or ejaculatory duct obstruction. RESULTS: Followup was available in 43 of the 49 patients (88%). Patency rates were 87% in the bilateral epididymovasostomy group, 69% in the unilateral group and 81% overall. Pregnancy rates were 43% in the bilateral and 23% in the unilateral group. While higher patency rates were observed for proximal anastomoses, higher pregnancy rates were observed for distal anastomoses. Intraoperative epididymal fluid quality correlated with patency, that is motile sperm in the epididymal aspirate correlated with postoperative patency (p <0.05). There was no correlation between fluid quality and pregnancy rates. Postoperative semen analyses demonstrated higher sperm density and higher motility in the pregnant versus nonpregnant groups. CONCLUSIONS: Epididymovasostomy may be performed in patients with obstructive azoospermia unrelated to vasectomy with high patency and good pregnancy rates. Intraoperative epididymal fluid quality can be predictive of patency. There was a trend towards higher pregnancy rates for distal anastomosis. There were no pregnancies when anastomosis was at the caput epididymis on both sides.
PURPOSE: Peyronie's disease is a connective tissue disorder resulting in fibrotic plaque formation on the tunica albuginea of the penis. One approach to repair consists of plaque excision and patching with one of many potential patch materials. Because the optimal patch material for covering the resultant defect has not been determined, this study compares histological and cavernosometric changes in the penis as a result of the placement of three different types of patch grafts used in surgery for Peyronie's disease. MATERIALS AND METHODS: Eleven mongrel dogs were divided into three groups, each receiving a different patch material (superficial dorsal penile vein, silicone fabric, and dermabraded preputial flap). Each dog had dynamic infusion cavernosometry (DIC) performed prior to placement of the patch over a 6 x 3 mm. defect surgically created in the tunica albuginea. Three months later, DIC was repeated prior to sacrifice. Histology of the penis was examined using Masson's trichrome, and hematoxylin and eosin stains. RESULTS: The only difference among the cavernosometric parameters (preop versus postop) was a higher initial pressure in the dermabraded preputial flap group postoperatively. The dogs undergoing vein patch had moderate fibrosis with apparent reformation of the tunica albuginea over the patch site. The normal venous architecture of the graft was no longer recognizable. Those dogs receiving a silicone patch had moderate fibrosis with a fibrous sheath of compressed histiocytes and fibroblasts enveloping the graft site. Finally, the dermabraded preputial flap patch group had mild-moderate fibrosis with focal loss of the cavernosal space underlying the flap. CONCLUSIONS: We feel that continued use of the vein patch for repair of Peyronie's disease is warranted.
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PURPOSE: We have recently demonstrated that computer assisted image analysis of paraffin embedded testicular tissue based on deoxyribonucleic acid content and morphology characteristics is an effective method for the quantitative assessment of spermatogenesis. We assess the use of testicular touch preparation image analysis as a technique for quantification of spermatogenesis. MATERIALS AND METHODS: Air dried, touch imprints of testicular tissue from obstructed azoospermic and severely oligozoospermic patients were obtained at the time of biopsy. Image analysis using a filter based on deoxyribonucleic acid content and cellular morphological characteristics was performed on Feulgen stained touch preparation imprints as well as paraffin embedded sections. RESULTS: Image analysis of 52 testicular touch preparations from 48 azoospermic or severely oligozoospermic men revealed significant differences (p < 0.05) in the percentages of spermatid and spermatozoa, and 2N and 4N cells among seminiferous tubules exhibiting the 5 diagnostic categories of obstruction with normal spermatogenesis, maturation arrest at the spermatocyte stage, maturation arrest at spermatid stage, hypospermatogenesis and Sertoli cell only. Similar differences were observed in the image analysis data of the corresponding paraffin embedded testicular sections. CONCLUSIONS: Computer assisted image analysis of testicular touch preparation is an effective quantitative method of spermatogenesis evaluation.
PURPOSE: We prospectively examined the effect of varicocelectomy on standard semen parameters and Kruger strict morphology, including site of specific sperm defect. MATERIALS AND METHODS: Kruger strict morphology and routine semen analysis were performed in a blinded fashion before and a minimum of 4 months after varicocelectomy in 61 subfertile men with a primary diagnosis of varicocele. RESULTS: Sperm motility, total number of motile sperm, and percentage and total number of sperm with normal strict morphology were significantly increased after varicocele repair. Average density was also increased, while volume and forward progression were unchanged. The percentage of normal head strict morphology was significantly improved, whereas tail and neck morphology did not reflect similar changes. CONCLUSIONS: Varicocele repair in subfertile men improves Kruger strict morphology. In addition, motility and total motile sperm are significantly improved after repair. Since the stoichiometry of the sperm head is crucial to egg and sperm interaction, this decrease in head defects may be partially responsible for the increase in pregnancy rates after varicocele repair.
The treatment of severe male factor infertility has seen remarkable advances in the last five years with the introduction and widespread use of intracytoplasmic sperm injection (ICSI). Although ICSI represents one of the most important advances in the treatment of the subfertile male, significant concerns exist regarding the potential for transmission of abnormal genes to the offspring because many of the natural barriers to conception have been bypassed. Because these couples were not able to conceive prior to ICSI, the long-term genetic consequences in these offspring are largely undefined at this time. Genetic abnormalities related to male infertility need to be considered in terms of being (1) causative for male infertility and (2) potentially transmissible to the offspring. Reasons for pursuing a genetic evaluation include (1) establishing a diagnosis, (2) establishing a possible genetic origin, (3) clarifying the pattern of inheritance, and (4) providing information on natural history, variation and expression. The three most common known genetic factors related to male infertility are cystic fibrosis gene mutations leading to congenital absence of the vas deferens, Y-chromosome microdeletions leading to spermatogenic impairment, and karyotype abnormalities. When congenital bilateral absence of the vas deferens with azoospermia is encountered, cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations are commonly the underlying cause. When testicular failure is manifest by azoospermia or severe oligoszoospermia, Y-chromosome microdeletions may be present in approximately 10-15 per cent of otherwise normal appearing men. Karyotyping can uncover potentially transmissible genetic abnormalities in the infertile male including structural chromosomal disorders such as Klinefelter's (classic 47,XXY), mixed gonadal dysgenesis, chromosomal translocations and XYY syndromes. Finally, potential male infertility genes in animal models are reviewed. Without question, advances in clinical and basic research raise scientific and social issues that must be addressed.
Nonsurgical measures have replaced penile prostheses as first-line treatment. In addition to intracavernous injection therapy and vacuum/constriction devices, options now include urethral suppositories.
Numerous advances in technology have been made in the last several years in the diagnosis and treatment of the infertile man. Using case presentations, this article highlights these important new developments and reviews the basics of a comprehensive male infertility evaluation. The use of ultrasound as a critical, indispensable, yet noninvasive tool in the evaluation of possible male reproductive tract obstruction is discussed. Since assisted reproductive techniques (ARTs) have become increasingly important in the management of the otherwise untreatable infertile man, specialized testing of sperm function, e.g., the sperm penetration assay (SPA), and strict morphology assessment are often useful prior to the initiation of some of these assisted reproductive procedures such as intrauterine insemination (IUI) or in vitro fertilization (IVF). Testicular touch preparation cytology and image analysis are also important additions to routine testicular biopsy for quantifying the extent of spermatogenesis. Finally, the revolutionary micromanipulation procedure of intracytoplasmic sperm injection (ICSI) has forever changed the practice of andrology by enabling men previously thought to be irreversibly infertile the chance to initiate their own biologic pregnancy.
PURPOSE: To determine the prevalence of cystic lesions of the prostate involving the ejaculatory ducts using transrectal ultrasound (TRUS). MATERIALS AND METHODS: The prevalence of cystic lesions of the prostate involving the ejaculatory ducts was determined in a prostate cancer screening group and also in an "at risk" population of men with infertility. RESULTS: Cystic lesions of the prostate involving the ejaculatory ducts as detected by TRUS were detected in 5.0% (20 of 400 consecutive men) in a prostate cancer screening population. In contrast, these abnormalities were present in 17.0% (23/135) of the "at risk" infertile men who had TRUS performed. CONCLUSIONS: This is the largest series to date defining the prevalence of TRUS-identified cystic lesions of the prostate in a non-infertility population. While cystic lesions of the prostate involving the ejaculatory duct are uncommon in an otherwise healthy and fertile male, their prevalence increases in infertile men whose examination and semen analyses make them "at risk" for having ductal obstruction.
OBJECTIVE: To determine, using an in situ end-labeling technique, whether the frequency of apoptosis is increased in testis biopsy specimens that demonstrate abnormal spermatogenesis. DESIGN: Immunohistochemical analysis was performed on archived paraffin-embedded testis biopsy specimens. Apoptotic indices, defined as the number of apoptotic bodies per the total number of cells or the number of Sertoli cells, were calculated after counting all the intratubular spermatogenic cells and Sertoli cells in 20 tubules. SETTING: Major academic male factor infertility clinic. PATIENT(S): Forty-eight testis biopsy specimens were obtained for routine clinical purposes from 38 men with azoospermia or severe oligozoospermia. INTERVENTION(S): In situ end-labeling was performed on archived paraffin-embedded testis biopsy specimens using terminal deoxynucleotidyl transferase. MAIN OUTCOME MEASURE(S): Apoptotic indices. RESULT(S): Significantly increased apoptotic indices were observed in patients with spermatocyte arrest, spermatid arrest, and hypospermatogenesis compared with patients with normal spermatogenesis and the Sertoli cell-only pattern. CONCLUSION(S): In situ end-labeling of testis biopsy specimens from infertile men demonstrates increased apoptosis in maturation arrest and hypospermatogenesis states compared with normal spermatogenesis and the Sertoli cell-only pattern. This unique observation implicates a prominent role for this form of programmed cell death in the pathophysiology of maturation arrest and hypospermatogenesis states.