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Biomedical subjects

J Rajfer

Publications and source records attributed to J Rajfer.

At least 127 records · Page 7Linked to original sources

Vasectomy.

In summary, a vasectomy is a safe, simple, and effective method of male contraception without any known long-term health hazards. Because of its simplicity, it is performed in more than 500,000 patients per year, mainly in a physician's office, making it a very cost-effective contraceptive method. With the introduction of the microscope into the operating suite of the urologist, this procedure that was once considered permanent is amenable to reversal at a later date.

Antibody Formation↗

Infection patterns in cyclosporine-treated cadaveric renal transplant patients.

Immunosuppression with Cs regimens has not significantly altered infection patterns relative to earlier modalities. However, reports of increased infection, especially with CMV/PCC, are not borne out in our experience both in numbers and timing of infections. Patients on low-dose Cs immunosuppression do continue to acquire infectious complications but, in general, rarely will lose their grafts or lives.

Cyclosporins↗

The current role of pre-transplant blood transfusions and tissue typing in cadaveric renal transplantation.

In a retrospective analysis of 74 consecutive cadaveric renal transplants performed at our center during a 38-month period we assessed the influence of random blood transfusions and tissue matching on graft and patient survival. All patients received cyclosporine and low dose prednisone with or without azathioprine as immunosuppressive therapy. Actual patient survival was 100 per cent at 1 year and actuarial 1-year graft survival was 82 per cent. Random blood transfusions and histocompatibility matching at the HLA-DR locus did not influence graft survival. Matching at 2 or more HLA-A and B loci was associated with a significant detrimental influence (p less than 0.05) on graft survival. We conclude that the use of cyclosporine-based immunosuppression overcomes much of the adverse effect of poor tissue matching and may obviate the need for random blood transfusions in cadaveric renal transplantation during the first year of engraftment.

Azathioprine↗

Gonadoblastoma: unusual presentation in a patient lacking persistent müllerian ducts.

We report a patient with a disorder of sexual differentiation who presented with a 46,XY karyotype, absent internal Müllerian ducts, a vaginal pouch, hypospadias, and bilateral cryptorchidism with a gonadoblastoma in one testis. A human chorionic gonadotropin stimulation test and tissue 5-alpha-reductase and androgen receptor assays were normal. Except for the absence of internal Müllerian ducts, this patient most closely resembles the disorder of dysgenetic male pseudohermaphroditism (DMP). On this basis, we hypothesize that the internal Müllerian ducts in DMP may manifest anywhere along a spectrum that extends from normal to complete absence of structures depending on the degree of gonadal dysgenesis. This case also illustrates the importance of testicular biopsy in patients with dysgenetic testes because of the high likelihood of germ cell neoplasms in these gonads.

Disorders of Sex Development↗

Inhibition of testicular testosterone biosynthesis following experimental varicocele in rats.

In an attempt to determine whether defective testicular testosterone (T) biosynthesis may be associated with a varicocele, an experimental study was performed in adult rats whereby a unilateral left varicocele was surgically created. At 2, 4, 8, and 12 wk following the creation of the varicocele, intratesticular T as well as the activities of three (17 alpha-hydroxylase, 17,20-desmolase, and 17 beta-hydroxysteroid dehydrogenase) of the five enzymes in the delta 4 pathway of testicular T biosynthesis were measured. Intratesticular T (ng/g testis +/- SEM) in the left testis decreased significantly from 121 +/- 21 in the control group to 59 +/- 8 in the two-wk varicocele group (p less than 0.01), and remained significantly suppressed throughout the experimental period. The T concentrations in the right testis paralleled those in the left in both the control and varicocele animals. At 2 wk following the creation of the varicocele, the activity (nmol/min/testis +/- SEM) of the 17,20-desmolase enzyme decreased significantly, from 115 +/- 8 in the left testis of control rats to 87 +/- 6 in the left testis of the varicocele animals (p less than 0.025), and remained low throughout the 12 weeks of the study. The activity of the 17 alpha-hydroxylase enzyme was significantly decreased at the 8th and 12th weeks of the study, while the 17 beta-hydroxysteroid dehydrogenase activity did not show any significant change during the study period. The enzyme activities in the right testis paralleled those in the left testis.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Cyclosporine inhibits testosterone biosynthesis in the rat testis.

To determine whether the immunosuppressive agent cyclosporine (CsA) has an effect on testicular androgen function in the male rat, four groups of adult animals were treated daily for 28 days with either orange juice or three doses of CsA (7.5, 15, or 30 mg/kg X day). Twenty-four hours after the last dose of CsA, the animals were killed and the following parameters were measured: testis, seminal vesicle, and ventral prostate weights; serum levels of CsA, creatinine, testosterone (T), and LH; and intratesticular levels of pregnenolone, progesterone, 17 alpha-hydroxyprogesterone, androstenedione, and T. There were no differences between the control (orange juice) and the three CsA-treated groups with respect to serum creatinines and testis, seminal vesicle, and ventral prostate weights. Serum T decreased significantly in the 15 and 30 mg/kg CsA-treated groups. The intratesticular T level decreased significantly only in the 15 and 30 mg/kg CsA-treated groups. In the 15 and 30 mg/kg CsA-treated groups, the intratesticular pregnenolone, progesterone, and 17 alpha-hydroxyprogesterone levels all showed a significant decline compared to controls. There was no significant change in the androstenedione levels in any of the CsA-treated groups. To determine whether the decrease in T production by the testis exposed to CsA is via inhibition of the hypothalamic-pituitary axis, serum LH was measured in all four groups. Serum LH decreased significantly only in the 15 and 30 mg/kg CsA-treated groups. These data suggest that oral CsA administration in doses greater than 15 mg/kg X day results in diminished intratesticular T production that appears to be mediated via inhibition of pituitary LH function.

17-alpha-Hydroxyprogesterone↗

Lack of a direct effect of gonadotropin hormone-releasing hormone agonist on human testicular steroidogenesis.

In an attempt to determine whether the chronic administration of GnRH agonist (GnRH-A) has a direct inhibitory effect on testicular steroidogenesis in the human, the testes of four men with disseminated prostatic cancer who were treated with GnRH-A daily for at least 1 yr were assayed for intratesticular pregnenolone (5-pregnen-3 beta-ol-20-one), progesterone, dehydroepiandrosterone, 17 alpha-hydroxypregnenolone (5-pregnen-3 beta 17 alpha-diol-20-one), 17 alpha-hydroxyprogesterone, androstenedione, and testosterone (T). In addition, testicular 17 alpha-hydroxylase, 17,20-desmolase, and 17 beta-hydroxysteroid dehydrogenase enzyme activities of the delta 4 pathway were measured. These intratesticular steroids and enzyme activities from four GnRH-A-treated patients were compared to those in five men (controls) who were orchiectomized as the primary treatment for their disseminated prostatic cancer and in three other men who were treated for 3-12 months with GnRH-A daily but received, in addition to the daily GnRH-A, 1000 IUhCG, im, every other day for 3 days immediately before their salvage orchiectomy, which was performed when their disease progressed. In the control group, the delta 5-steroids, particularly dehydroepiandrosterone and pregnenolone, represented the majority of the intratesticular steroids. Compared to control values, all intratesticular steroids except delta 4-P (for which there was no difference) were significantly lowered by treatment with GnRH-A. Intratesticular T was reduced by 98% from 328 +/- 139 (+/- SEM) ng/g testis in the control group to 8 +/- 3 in the GnRH-A-treated group (P less than 0.01). The additional treatment with hCG for 3 days in the GnRH-A-treated group reversed the inhibition of all steroids to either control or above control levels, with intratesticular T rising to 1144 +/- 273 ng/g testis. A similar trend was found for all three enzymatic activities, i.e., GnRH-A alone inhibited each of the enzymatic activities, whereas the addition of hCG reversed this inhibition by GnRH-A. These data indicate that the chronic administration of GnRH-A to elderly men results in inhibition in both the delta 4 and delta 5 pathways, with a subsequent decrease in the intratesticular T concentration. The ability of exogenous hCG to reverse both the reduction in delta 4 and delta 5 intratesticular steroid content and the intratesticular enzyme activities induced by GnRH-A treatment supports the concept that GnRH-A does not have a direct inhibitory effect on testicular T biosynthesis.

17-Hydroxysteroid Dehydrogenases↗

Hormonal therapy of cryptorchidism. A randomized, double-blind study comparing human chorionic gonadotropin and gonadotropin-releasing hormone.

We conducted a randomized, double-blind study comparing intranasal gonadotropin-releasing hormone (1.2 mg per day for 28 days) with parenteral human chorionic gonadotropin (3300 IU per week for four weeks) in the treatment of cryptorchidism in 33 boys one to five years old (29 with unilateral and 4 with bilateral cryptorchidism). Testicular descent into the scrotum occurred in 3 of the 16 patients (19 percent) treated with gonadotropin-releasing hormone and in 1 of the 17 (6 percent) treated with human chorionic gonadotropin (P = 0.23). The mean luteinizing hormone and testosterone levels were similar in both groups before treatment. During treatment, the testosterone levels were significantly increased in both groups, but higher levels occurred in the group treated with human chorionic gonadotropin (P less than 0.05). In a parallel (but uncontrolled) study of five boys with retractile testes (defined as a nonscrotal testis that could be manipulated into the bottom of the scrotum) who were originally excluded from the main protocol but were treated with the same regimen of human chorionic gonadotropin, descent into the scrotum occurred in all patients. We conclude that hormonal therapy with either gonadotropin-releasing hormone or human chorionic gonadotropin is, in most cases, ineffective in promoting testicular descent of true cryptorchid testes. However, short-term treatment with human chorionic gonadotropin is very effective in producing descent of retractile testes. These results suggest that the wide discrepancies in apparent efficacy in previous trials of hormonal therapy of cryptorchidism may have been due to inclusion in those studies of various proportions of patients with retractile testes.

Administration, Intranasal↗

Luteinizing hormone and follicle-stimulating hormone responses to intransal gonadotropin-releasing hormone.

For determination of the dose-response relationships of plasma luteinizing hormone (LH) and follicle-stimulating hormone (FSH) to the intranasal administration of gonadotropin-releasing hormone (GnRH), normal adult men were administered doses of 100, 200, 400, and 800 micrograms of GnRH on separate days, and plasma LH and FSH were measured before and after nasal insufflation of GnRH. Plasma LH was increased after a minimum dose of 200 micrograms GnRH. Median peak plasma LH levels occurred 30 minutes after intranasal GnRH and followed a log-dose relationship. When compared with intravenous GnRH, the biopotency of intranasal GnRH at the 200-, 400-, and 800-microgram doses was 1.1%, 2.3%, and 6.2%, respectively. Plasma FSH levels rose significantly only after the highest (800-micrograms) intranasal GnRH dose. From these data, we conclude that in eugonadal adult men the minimal effective dose of intranasal GnRH to elicit a significant pituitary (LH) response is 200 micrograms and that the relative efficacy of intranasal GnRH increases with the dose. In spite of the apparently low biopotency for intranasal GnRH, this route of administration may be considered as an alternative to the parenteral mode of GnRH delivery, and the lower biopotency can be partly overcome by increasing the dose.

Adult↗

Comparison of the efficacy of subcutaneous and nasal spray buserelin treatment in suppression of testicular steroidogenesis in men with prostate cancer.

The comparative efficacy of subcutaneous injections and intranasal spray in the maintenance of suppression of testicular function in men with advanced prostatic cancer treated with a gonadotropin-releasing hormone (GnRH) agonist, Buserelin, was evaluated in a nonrandomized clinical trial. After a common induction period of 1 week's treatment with 500 micrograms three times daily by subcutaneous injection, patients were allocated into one of two groups for maintenance therapy with either subcutaneous (200 micrograms once daily) or intranasal (400 micrograms nasal spray three times daily) Buserelin therapy. Plasma luteinizing hormone (LH) and sex steroid (testosterone [T], dihydrotestosterone [DHT], and estradiol [E2]) patterns were studied before the start and at days 1, 7, and 14 and months 2, 4, 6, and 12 on maintenance regimens. During the maintenance therapy, age-adjusted T levels were markedly suppressed to near-castrate levels in both treatment groups. Despite this marked suppression, age-adjusted T levels were consistently lower in men treated with the subcutaneous regimen from the 2nd week to the 12th month of treatment in morning pooled specimens as well as in detailed sampling over a 24-hour period after 12 months of continuous treatment. A similar pattern of enhanced suppression by the subcutaneous regimen was also observed for age-adjusted DHT, but not E2, levels during the study. Neither the magnitude nor the time course of T suppression by GnRH analog treatment could be entirely explained by the nature of the decline in plasma LH levels, which fell much less and more gradually over a 12-month period.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Intranasal↗

Pyelovesicostomy as a form of urinary reconstruction in renal transplantation.

The development of ureteral obstruction or ureteral fistula formation in the renal transplant recipient usually requires surgical repair. This involves reconnecting the donor ureter to either the recipient ureter (ureteroureterostomy) or bladder (ureteroneocystostomy), or creating an anastomosis between the renal pelvis and recipient native ureter (pyeloureterostomy). Occasionally, the donor or recipient ureter is absent, necrotic or diseased so that a ureteroureterostomy, ureteroneocystostomy or pyeloureteral anastomosis cannot be performed. In 8 such cases we have performed a direct anastomosis between the donor renal pelvis and recipient bladder (pyelovesicostomy) with a followup of between 2 months and 11 years. In all 8 patients there has been no deterioration in renal function attributed to obstruction at the anastomotic site or to the free reflux between the bladder and renal pelvis. Because of the excellent short-term and long-term results of pyelovesicostomy, this procedure should be considered as an excellent alternative to pyeloureterostomy, ureteroureterostomy and ureteroneocystostomy in the reconstruction of the upper urinary tract of the renal transplant patient.

Adult↗

Association between abdominal wall defects and cryptorchidism.

To determine whether intra-abdominal pressure may have a role in the process of testicular descent in man, we reviewed retrospectively the records of all male infants who presented during a 10-year period with severe abdominal wall defects, such as gastroschisis (28), omphalocele (29) and umbilical hernia (53), and calculated the incidence of cryptorchidism in these patients. The incidence of cryptorchidism at birth and at 1 year after birth was 18 and 15 per cent, respectively, in patients with gastroschisis, 52 and 33 per cent, respectively, in those with omphalocele, and 6 and 6 per cent, respectively, in those with umbilical hernia. For all 3 disorders the incidence of cryptorchidism was higher than in documented historical controls. From these data we conclude that in male infants there is an association between these 3 abdominal wall defects and cryptorchidism. The demonstration that intra-abdominal pressure is lowered significantly by these abdominal wall defects would suggest a possible role for intra-abdominal pressure in the process of testicular descent in man.

Abdominal Muscles↗

Cytomegaloviral epididymitis in a patient with the acquired immune deficiency syndrome.

We report on a patient with cytomegaloviral epididymitis and the acquired immune deficiency syndrome. The diagnosis was suggested by epididymitis that was refractory to antibiotics, and by isolation of cytomegalovirus from the urine and semen. The definitive diagnosis was made with immunohistochemical staining for cytomegaloviral antigens in the epididymal ductal cells. Because of the ineffectiveness of antimicrobial agents in this disorder, epididymectomy is the current treatment of choice.

Acquired Immunodeficiency Syndrome↗