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Biomedical subjects

A D Seftel

Publications and source records attributed to A D Seftel.

At least 37 records · Page 2Linked to original sources

Effects of subinguinal varicocele ligation on sperm concentration, motility and Kruger morphology.

PURPOSE: We examined the effects of varicocelectomy on semen parameters in 30 subfertile men, with emphasis on potential changes in sperm count, motility and morphology as measured by Kruger's strict morphologic criteria. MATERIALS AND METHODS: A total of 30 patients underwent subinguinal varicocelectomy (25 bilateral and 5 unilateral). Preoperative and postoperative sperm density, motility and morphology were analyzed. Preoperative follicle-stimulating hormone, luteinizing hormone and testosterone levels were measured and compared to those of fertile volunteers enrolled in our sperm donation program. Pregnancy rates after varicocelectomy were also examined: The Wilcoxon signed rank test was used to measure levels of statistical significance in all analyses. RESULTS: We found that sperm density and motility improved significantly (p < 0.05) without concomitant changes in strict morphology (p > 0.05) only in men with clinical bilateral varicoceles. No differences were observed in values among testosterone, follicle-stimulating hormone and luteinizing hormone levels of the fertile control group and preoperative varicocele patients. Of 30 patients 12 (40%) had successful, full-term pregnancies, including 6 via natural cycle intercourse, 5 (43%) by in vitro fertilization embryo transfer and 1 by intracytoplasmic sperm injection. CONCLUSIONS: Although sperm morphology as measured by strict morphologic criteria does not improve after varicocelectomy, there were highly significant changes in motility and concentration. Hormonal differences are not likely to have a role in or be reflective of pathophysiology of varicocele induced male infertility. The recent observation that sperm motility may be an independent or additive predictive factor for fertilization and pregnancy supports the need for continued varicocele repair independent of the lack of varicocelectomy effect on Kruger morphology.

Female↗

Adrenal metastases from renal cell carcinoma: role of ipsilateral adrenalectomy and definition of stage.

OBJECTIVES: We undertook this study to establish criteria for adrenalectomy in patients with renal cell carcinoma. METHODS: We retrospectively reviewed the records of 162 patients undergoing radical nephrectomy from 1979 to 1993 at University Hospitals of Cleveland. Simultaneous ipsilateral adrenalectomy was performed in 57 patients (35%). RESULTS: Three of these 57 patients (5.3%) had ipsilateral adrenal metastases. All 3 patients had large, left-sided, upper-pole tumors that extended through the renal capsule (Stage T3a). All 3 patients with adrenal metastases had progression to disseminated disease, with an average time to progression of 7.2 months, whereas only 13 (24%) of the 54 patients without adrenal metastases developed metastatic disease (none to adrenal), with an average time to progression of 27.6 months. No patient with organ-confined disease (Stage T1 or T2) or extracapsular disease in the midkidney or lower pole had adrenal metastases identified histologically. CONCLUSIONS: The prognosis is poor for renal cell carcinoma with ipsilateral adrenal involvement, even with complete removal. Because of this poor prognosis, we believe that adrenal involvement should constitute a separate stage category. We propose that patients with ipsilateral adrenal metastases via direct extension should be classified as having pathologic Stage pT3d. If the patient has an ipsilateral adrenal metastasis not via direct extension, contralateral adrenal metastasis, or bilateral adrenal metastases, the pathologic stage should be M1. Ipsilateral adrenalectomy should only be performed if a lesion is seen preoperatively on computed tomographic scan or if gross disease is seen at the time of nephrectomy although its removal may not benefit the patient.

Adrenal Gland Neoplasms↗

Advanced glycation end products in human penis: elevation in diabetic tissue, site of deposition, and possible effect through iNOS or eNOS.

OBJECTIVES: We hypothesized that advanced glycation end product (AGE) formation contributes to erectile dysfunction (ED) by quenching nitric oxide. Our first goal was to identify the specific AGE pentosidine in the diabetic human penis. Because AGE-mediated effects may involve inducible nitric oxide synthase (iNOS), we performed immunohistochemical and Western blot analysis of diabetic and nondiabetic human penile tissue for iNOS. Finally, because AGEs may act intracellularly to affect proteins, we set out to identify endothelial NOS (eNOS) in the human penis as an initial step in examining a possible intracellular interaction between eNOS and AGEs. METHODS: We performed high-performance liquid chromatographic analysis of diabetic human penile corpus cavernosum and serum for pentosidine and performed immunohistochemical, electron microscopic (EM), and Western blot analysis of the diabetic and nondiabetic penile corpus cavernosum and tunica for pyrraline, iNOS, and eNOS (and neural NOS [nNOS] for comparative purposes) via standard methods. RESULTS: We found a significant elevation of pentosidine in the penile tissue but not the serum of diabetic patients (average age 55.6 +/- 2.3 years) compared with that of nondiabetic patients (average age 61.8 +/- 3.6 years). Pentosidine was 117.06 +/- 9.19 pmol/mg collagen in the diabetic tunica versus 77.58 +/- 5.5 pmol/mg collagen in the nondiabetic tunica (P < 0.01) and 74.58 +/- 8.49 pmol/mg collagen in the diabetic corpus cavernosum versus 46.59 +/- 2.53 pmol/mg collagen in the nondiabetic corpus cavernosum (P < 0.01), suggesting a tissue-specific effect of the AGEs. We localized the site of deposition of the specific AGE pyrraline to the human penile tunica and the penile corpus cavernosum collagen. Immunohistochemical and EM analysis localized eNOS and iNOS to the cavernosal endothelium and smooth muscle. Western blot analysis in 6 patients revealed the following: iNOS, but no eNOS, in penile tissue from 1 insulin-dependent diabetic man; eNOS only in 1 man after radical prostatectomy; both eNOS and iNOS in 2 men with Peyronie's disease, as well as in 2 other men with impotence and hypertension. Finally, the specific iNOS inhibitor PNU-19451A significantly augmented relaxation of precontracted human cavernosal tissue, from 64.7% +/- 5.58 to 80.03% +/- 4.55 at 10 microM acetylcholine and 65.06% +/- 2.84 to 86.16% +/- 3.96 at 0.1 mM acetylcholine (n = 4, P < 0.002 and P < 0.02, respectively). CONCLUSIONS: AGEs are elevated in diabetic human penile tissue, but not in serum, and are localized to the collagen of the penile tunica and corpus cavernosum. We identified eNOS and iNOS in the human penile cavernosal smooth muscle and endothelium. The augmentation of cavernosal relaxation with a specific iNOS inhibitor, combined with the identification of iNOS protein, but not eNOS, in a patient with severe diabetes and ED, allows for speculation of a pathophysiologic mechanism for AGE-mediated ED via upregulation of iNOS and downregulation of eNOS. These data provide further insight into the mechanisms of advanced glycation end product-mediated ED and provide a foundation for further study.

Adult↗

Protease inhibitors and urolithiasis.

PURPOSE: We discuss the specific urological abnormalities associated with protease inhibitor therapy. MATERIALS AND METHODS: We report on a human immunodeficiency virus positive patient who was on protease inhibitor therapy and presented with renal colic. RESULTS: The stone passed spontaneously. Stone analysis was not consistent with any known composition of urinary calculus. CONCLUSIONS: The positive effects of protease inhibitors in human immunodeficiency virus positive patients mandate that the urological community become familiar with these drugs and the specific urological complications as the use of these drugs becomes widespread.

Adult↗

The role of gamma-glutamyl transpeptidase in the preoperative metastatic evaluation of renal cell carcinoma.

PURPOSE: We evaluated gamma-glutamyl transpeptidase as an indicator of metastatic disease in patients with renal cell carcinoma. MATERIALS AND METHODS: We reviewed the records of 53 patients with metastatic renal cell carcinoma, and compared serum alkaline phosphatase and gamma-glutamyl transpeptidase with the site of metastases. These results were then compared to those in 29 patients with clinically localized renal cell carcinoma. RESULTS: Overall gamma-glutamyl transpeptidase was elevated in 37 patients (69.8%) with metastatic disease, while alkaline phosphatase was elevated in 16 (30.2%, p < 0.025). Gamma-glutamyl transpeptidase was increased in more patients with hepatic metastases only than alkaline phosphatase (p < 0.025) and in all groups it was a better predictor of metastases than alkaline phosphatase. Gamma-glutamyl transpeptidase was also increased in significantly more patients with metastatic renal cell carcinoma (37 of 53) compared to 1 of the 27 with localized renal cell carcinoma (p < 0.001). CONCLUSIONS: Gamma-glutamyl transpeptidase was increased in a large percent of patients with metastatic renal cell carcinoma, and it was normal in the majority with localized renal cell carcinoma. We conclude that gamma-glutamyl transpeptidase should be included as well as alkaline phosphatase in the preoperative metastatic evaluation of patients with renal cell carcinoma. Elevated gamma-glutamyl transpeptidase should prompt a search for bone as well as liver metastases.

Adolescent↗

Nitric oxide relaxes rabbit corpus cavernosum smooth muscle via a potassium-conductive pathway.

We tested the hypothesis that acetylcholine-induced relaxation in cavernosal tissue is the result of nitric oxide production that alters K+ conductance. In the organ bath, acetylcholine- and sodium nitroprusside-induced relaxation of corpus cavernosum were significantly attenuated by tetraethylammonium. Basal [K+]i in cavernosal smooth muscle cells was 102 +/- 11 mM using a K+-sensitive fluorescent dye. Acetylcholine produced a decrease in [K+]i to 74 +/- 10 (n > 4, P < 0.05). Tetraethylammonium pretreatment blunted the acetylcholine- and sodium nitroprusside-induced decrease in [K+]i by 82%, (n > 5, P < 0.001), respectively. L-NMMA blunted the acetylcholine- and sodium nitroprusside-induced fall in [K+]i by 93% and 83% (n > 4, P < 0.001), respectively. These data suggest that acetylcholine-mediated cavernosal smooth muscle cells relaxation occurs through nitric oxide release with activation of K+ conductance.

Acetylcholine↗

Perineal abscess after embolization for high-flow priapism.

High-flow priapism is unusual and is most often due to blunt perineal trauma with resultant laceration of the cavernosal artery, creating an arteriocavernosal fistula. Although few cases have been reported, the consensus on management appears to be embolization of the fistula with autologous clot, alone or in combination with Gelfoam. We present a case of high-flow priapism treated in this manner. The embolized pseudoaneurysm evolved into an abscess that eventually spread to the perineum. The rarity of this entity and the postprocedural morbidity are reported.

Abscess↗

Age-related increase in an advanced glycation end product in penile tissue.

Nonenzymatic glycosylation (glycation) of proteins, often referred to as the Maillard reaction, has been proposed to play a role in age and diabetes-related processes by forming protein and DNA adducts and cross-links. These cross-links may contribute to erectile dysfunction by scavenging nitric oxide, which is needed for erection. As the basis for a possible role of the advanced Maillard reaction in age-related erectile dysfunction, we investigated the presence of the specific advanced glycation endproduct (AGE) pentosidine in penile corpus cavernosum tissue and penile tunica albuginea tissue as a function of age. A total of 23 penile tissue specimens were obtained at autopsy, from which 19 samples of tunica albuginea and 21 samples of corpus cavernosum were derived. In addition, 13 penile corporal and tunical specimens were procured at the time of insertion of a penile prosthesis, from which 12 tunica albugineal specimens and 10 samples of corpus cavernosum were derived. Collagen was extracted with acetic acid and pepsin digestion, and the final insoluble collagen product was acid-hydrolyzed with 6 N HCL for 24 h at 110 degrees C. Pentosidine was quantified by high-performance liquid chromatography using a reverse-phase column. The level of pentosidine (expressed in picomoles per milligram of insoluble collagen) was found to increase with age in cadaver as well as living penile corporal and tunical albugineal tissues. Best-fit analysis revealed an exponential increase in both types of cadaver penile tissue, with regression equations of y = 15.29 x 10(9.9e-3x), R2 = 0.79, being obtained in the tunica and y = 13.2 x 10(7.63e-3x), R2 = 0.56, in the corpora. These correspond to 6- and 4-fold increases in pentosidine levels from puberty to the age of 100 years (P < 0.05), respectively. Mean pentosidine levels were higher in the tunica than in the corpora. Comparison of pentosidine levels in the tunica versus the corpora revealed a weakly linear correlation (y = 24.88 + 1.08x, R2 = 0.32). Levels in the tunical and corporal specimens from the living human specimens fell with the predicted confidence intervals of the cadaveric tissue. Tunical specimens from patients who underwent repair or revision of a previously inserted penile prosthesis had very low levels of pentosidine. The exponential age-related increase in pentosidine observed in both types of penile tissue suggests an impairment of collagen turnover, which could be related to the advanced glycation reaction in aging. It is not known whether pentosidine itself is directly associated with erectile dysfunction, but its formation is usually accompanied by extensive tissue modification. Formation of advanced Maillard reaction products, which is greatly accelerated in aging, diabetes, and uremia, could contribute to erectile dysfunction in these syndromes.

Adult↗

Impotence associated with blunt pelvic and perineal trauma: penile revascularization as a treatment option.

Erectile dysfunction (impotence) is a well-known complication of blunt pelvic and perineal trauma. The mechanism of injury is usually related to the trauma itself, via shearing of the penile blood vessels in the pelvis, or via direct trauma to the blood vessels in the perineum. The diagnostic evaluation of these patients should include evaluation of the nervous supply of the penis, the penile arterial tree and the veno-occlusive mechanism. Penile revascularization is a reasonable treatment option for this group in that many injured patients are young and show arterial injury, with minimal or no veno-occlusive dysfunction. Proper patient selection and precise operative technique should allow for restoration of erectile dysfunction in these patients.

Humans↗

Focal inflammation of the corpus cavernosum in a diabetic man due to acute occlusion of the cavernous artery.

Inflammation of the penile corpus cavernosum is an unusual condition most often associated with an infectious process. We report on a diabetic man with localized inflammation of the corpus cavernosum resulting from acute occlusion of the cavernous artery. Diagnosis was made by exclusion and ultimately confirmed by penile angiography. Conservative measures led to resolution of this process.

Acute Disease↗

Delayed hypersensitivity reaction after infusion of nonionic intravenous contrast material for an excretory urogram: a case report and review of the literature.

Delayed adverse reactions to ionic and nonionic intravenous contrast media have been reported previously. We report a case in which delayed hypersensitivity to iohexol, a nonionic intravenous contrast agent commonly used in excretory urography, resulted in a bi-phasic allergic response. This reaction consisted of a mild post-infusion episode of urticaria, which preceded and was clinically distinct from a moderately severe dermatological eruption. The episode of urticaria was self-limited. The dermatological reaction was treated successfully with antihistamine therapy.

Aged↗

The evaluation and management of erectile dysfunction.

Significant progress has been realized in the evaluation and treatment of erectile disorders during the past 15 years. The establishment of interdisciplinary teams and evolution of treatment centers have led to comprehensive, state-of-the-art evaluation and multiple innovative treatment options. Limitations in our knowledge, however, remain because age-related standards for diagnostic tests are not available. In some cases, we remain humble and uncertain about the validity of our diagnostic methods and our ability to offer proper treatments. The field is not standing still, however, and we expect that further refinements in evaluation techniques based on new findings in physiology and fresh psychological and medical approaches will make erectile dysfunction more efficiently and effectively treatable.

Adult↗

A new protocol for the followup of renal cell carcinoma based on pathological stage.

There is no consensus concerning which laboratory and imaging studies should be obtained to assess patients after radical nephrectomy for renal cell carcinoma. We retrospectively reviewed 158 patients who underwent radical nephrectomy with a final pathological diagnosis of renal cell carcinoma. Of the patients 21 had node-positive or metastatic disease and 137 had no evidence of metastases at diagnosis. Of the latter group 19 had pathological stage T1N0M0, 82 stage T2N0M0 and 36 stage T3N0M0 (18 stage T3a, 10 stage T3b and 8 stages T3a and b) tumor. Disease recurred in 0%, 14.6% and 52.8% (50%, 44.4% and 75%) of the patients, respectively. The average interval to recurrence was 29.5 months (range 3.5 to 88.8) for patients with stage T2 carcinoma and 22 months (range 3 to 138) for those with stage T3 disease. Based upon our data, followup studies should include a symptom history, serum liver function studies and chest x-rays at defined intervals. Routine use of bone scans and computerized tomography does not appear to be necessary.

Adolescent↗