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Biomedical subjects

J Rajfer

Publications and source records attributed to J Rajfer.

At least 109 records · Page 6Linked to original sources

Testicular oximetry: a new method for the assessment of tissue perfusion and viability following torsion and detorsion.

This study evaluated the use of a polarographic surface PO2 electrode to assess testicular perfusion and viability following torsion and detorsion. Adult male Sprague-Dawley rats were divided into groups and subjected to unilateral testicular torsion and detorsion of varying degrees and durations. Rats subjected to sham torsion or 720 degrees torsion did not show significant decreases in testicular PO2 after 15 minutes, whereas those subjected to 1,080 degrees torsion or spermatic cord ligation uniformly decreased their testicular PO2 to 0 mm Hg within 10 minutes. Testicular PO2 values were similar in rats subjected to 60 minutes of 720 degrees torsion followed by detorsion and those undergoing 15 minutes of 1,080 degrees torsion and detorsion. Rats subjected to breathing 100% oxygen uniformly increased their testicular PO2 to an average of more than twice room-air values. However, rats subjected to 1,080 degrees torsion for 6 hours followed by detorsion did not increase their testicular PO2 when subjected to breathing 100% oxygen, whereas those subjected to 720 degrees torsion for 6 hours followed by detorsion did increase their testicular PO2 when subjected to breathing 100% oxygen. The latter rats did not show microscopic changes associated with acute testicular infarction, whereas the former did.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

Recovery of testicular blood flow following ligation of testicular vessels.

To determine whether initial ligation of the testicular vessels of the high undescended testis followed by a delayed secondary orchiopexy is a viable alternative to the classical Fowler-Stephens procedure, a series of preliminary experiments were conducted in the rat in which testicular blood flow was measured by the 133xenon washout technique before, and 1 hour and 30 days after ligation of the vessels. In addition, testicular histology, and testis and sex-accessory tissue weights were measured in 6 control, 6 sham operated and 6 testicular vessel ligated rats 54 days after vessel ligation. The data demonstrate that ligation and division of the testicular blood vessels produce an 80 per cent decrease in testicular blood flow 1 hour after ligation of the vessels. However, 30 days later testis blood flow returns to the control and pre-treatment value. There were no significant changes in testis or sex-accessory tissue weights 54 days after vessel ligation. Histologically, 4 of the surgically operated testes demonstrated necrosis of less than 25 per cent of the seminiferous tubules while 1 testis demonstrated more than 75 per cent necrosis. The rest of the tubules in all 6 testes demonstrated normal spermatogenesis. From this study we conclude that initial testicular vessel ligation produces an immediate decrease in testicular blood flow but with time the collateral vessels are able to compensate and return the testis blood flow to its normal pre-treatment value. These preliminary observations lend support for the concept that initial ligation of the testicular vessels followed by a delayed secondary orchiopexy in patients with a high undescended testis may be a possible alternative to the classical Fowler-Stephens approach.

Animals↗

Use of biopty gun for transcutaneous testicular biopsies.

Needle biopsies are being performed commonly as a substitute for open biopsy in certain patients in whom a tissue diagnosis is necessary to determine therapy. During the last few years the Biopty gun and its through-cut needle have evolved as a satisfactory method to perform prostate biopsy in a rapid and painless manner. To determine whether the Biopty gun could be used to perform testicular biopsies 7 patients underwent this procedure in an outpatient setting. The patients received cutaneous lidocaine and the special through-cut needle (already inserted in the gun) was inserted painlessly through this cutaneous wheal towards the tunica albuginea of the testis. The gun was fired and in less than a fraction of a second a biopsy was obtained. The needle was removed and the tissue was placed in Bouin's solution. In some patients more than 1 biopsy was performed. None of the biopsies took more than 5 minutes, none of the patients required postoperative analgesia and none felt untoward discomfort during the biopsy. All biopsies obtained adequate tissue to diagnose the presence of sperm. These results demonstrate that needle biopsy of the testis with the Biopty gun system is a cost-effective, rapid, safe, relatively harmless and effective way to obtain a testicular biopsy to identify the presence of sperm. With time this percutaneous method may supercede other open and percutaneous methods of testicular biopsy.

Adult↗

Effects of extracellular ionized calcium, diltiazem and cAMP on motility of human spermatozoa.

In order to elucidate the effects of ionized calcium and calcium channel blockers on human sperm motility, an in vitro study was conducted looking at the effects of exogenous calcium, ethylene diamine tetraacetic acid (EDTA), diltiazem and dibutyrl cyclic adenosine monophosphate (db-cAMP) on per cent motility and mean velocity of human sperm. Washed spermatozoa from 21 fertile donors were incubated with ionized calcium (zero, five, 10 and 50 mM), EDTA (one and 10 mM), diltiazem (one, 10, 100 microM and one mM) and cAMP (five mM). Per cent motility and mean velocity determinations were made at 10 and 120 min. by computerized analysis of videomicrographs. Over a wide range of extracellular ionized calcium concentrations (50 microM to 50 mM), per cent motility and mean velocity of human sperm were not stimulated or inhibited. At ionized calcium concentration less than 1 microM, achieved by addition of EDTA (10 mM), per cent motility decreased by 68% and 79% and mean velocity decreased by 44% and 48% compared to controls at 10 and 120 min. respectively (p less than 0.001). The decrease in mean velocity was reversible by addition of calcium to the EDTA (10 mM) sample to return ionized calcium to control concentration (0.5 mM). This reversibility suggests EDTA did not have a direct toxic effect on spermatozoa and that its action was mediated by changes in ionized calcium concentration. Diltiazem (one mM) decreased sperm mean velocity by 26% and 28% compared to controls at 10 and 120 min. respectively (p less than 0.01), but had no effect at lower concentrations (one, 10 or 100 microM). Db-cAMP (five mM) increased per cent motility by 25% and 20% and mean velocity by 36% and 34% compared to controls at 10 and 120 min. respectively (p less than 0.05). These results indicate that a minimum level of extracellular ionized calcium is essential to normal sperm motility and suggest that sperm are more dependent on the intracellular translocation of calcium ions for the regulation of motility than on the extracellular ionized calcium concentration. While db-cAMP does significantly increase per cent motility and mean velocity of human sperm, its clinical usefulness for the treatment of male infertility remains to be demonstrated.

Bucladesine↗

Anatomy of penile venous drainage in potent and impotent men during cavernosography.

Recent data suggest that approximately 80 per cent of the men with vasculogenic impotence have evidence of failure to store blood (venous leakage) within the corpora cavernosa. To identify the venous channels into which corporeal blood drains in impotent men, we performed cavernosograms after intracorporeal injection of papaverine in 44 consecutive men presenting with erectile dysfunction and these were compared to studies in 10 potent men. The cavernosograms were examined for evidence of venous drainage from the penis and the site of leakage was identified. It was determined that among the impotent population with vasculogenic impotence 37 of 40 evaluable men (92.5 per cent) demonstrated contrast medium in the venous system draining the penis: the deep dorsal vein was visualized in 55 per cent, proximal cavernosal and crural veins in 55 per cent, deep dorsal and proximal veins in 22.5 per cent and corpus spongiosum in 25 per cent. Only 2 of the 10 potent men demonstrated contrast medium in the venous channels draining the penis. From these observations we conclude that in men suspected of having venogenic impotence identification of the drainage vessels by cavernosography appears to be important in planning any surgical approach to occlude these veins. However, the finding of a venous leak by cavernosography must not be considered a sine qua non diagnosis of venogenic impotence, since a certain percentage of potent men will demonstrate this radiographic finding.

Adult↗

Cyclosporine augments renal mitochondrial function in vivo and reduces renal blood flow.

The in vivo action of cyclosporine A (CS) on rat renal cortical mitochondria was investigated. CS (30 mg.kg-1.day-1) given orally to rats for 30 days caused an augmentation of renal mitochondrial oxidative phosphorylation. The ADP-stimulated respiratory rate was increased by 37.0% with glutamate plus malate as respiratory substrates (P less than 0.025) but not with succinate-supported respiration, indicating enhancement of mitochondrial complex I activity. This reaction may be a response to the 32.5% reduction of renal blood (P less than 0.005) in the CS-treated group, possibly serving to maximize ATP synthesis during ischemia. Ligation-induced decreases in renal blood flow also resulted in enhancement of mitochondrial complex I activity.

Animals↗

Declining incidence of wound infection in cadaveric renal transplant recipient.

Over a five-year period 100 cadaveric renal transplants were performed. In 91 of these recipients, a prophylactic parenteral antibiotic (cefoperazone) was administered and closed wound drainage was used. Of these 91 patients, 33 received azathioprine/prednisone immunosuppression, whereas cyclosporine/prednisone with or without azathioprine was used in the remaining 58. The incidence of wound infections was significantly reduced from 12 per cent (4/33) in the azathioprine group to 1.7 per cent (1/58) in the cyclosporine group (p less than 0.01). When conventional immunosuppression (azathioprine/prednisone) is employed in renal transplantation, triple antibiotic prophylaxis that includes an aminoglycoside is most effective in preventing wound infections. A single non-nephrotoxic antibiotic, cefoperazone, offers similar protection in the cyclosporine/prednisone-treated renal transplant recipient.

Cadaver↗

Prevalence of corporeal venous leakage in impotent men.

To provide insight into the prevalence of corporeal venous leakages as a factor in impotence, 44 consecutive impotent men who failed to achieve an erection after intracorporeal papaverine injection underwent dynamic infusion cavernosometry and cavernosography. If venous leakage is defined as either a failure to increase intracorporeal pressure greater than the systolic blood pressure or a rapid decrease in intracorporeal pressure after cessation of saline infusion during cavernosometry, 30 of the 44 men (68 per cent) fall into this category. If cavernosography (43 men) is used to define the presence of a venous leakage in these impotent patients 37 (86 per cent) fall into this category. These data support recent observations that there is a high incidence of venous leakage as defined by these criteria in men with organic impotence. The significance of these findings can be determined only once a similar study in age-matched potent men is performed.

Adult↗

Cadaveric renal transplantation: surgical results and expectations in the cyclosporine era.

During a 36-month period 100 patients received 104 cadaveric renal transplants with cyclosporine-based immunosuppression. Of the patients 26 required 31 additional operations. Of the 19 secondary operations performed 1 month after transplantation 18 were emergency in nature, whereas beyond this period the majority of the procedures were elective. Both deaths in this series were related to the operation. Only 1 graft loss was directly attributed to a secondary operation. The patient undergoing cadaveric renal transplantation is at significant risk (25 per cent) of requiring at least 1 additional operation. However, despite this high probability of reoperation, graft loss and patient death after such procedures should be rare.

Adult↗

Characterization of cyclic nucleotide and inositol 1,4,5-trisphosphate-sensitive calcium-exchange activity of smooth muscle cells cultured from the human corpora cavernosa.

Smooth muscle-mediated expansion and contraction of the vascular sinusoids of the corpora cavernosa may modulate male erectile function. To elucidate the biochemical events that control erection by promoting or inhibiting contraction of cavernosal smooth muscle, tissue from a potent man was grown in cell culture. The cells grew as noncontractile cultures, but had the following smooth muscle cell properties: These cells expressed desmin, the muscle cell-specific intermediate filament protein. They accumulated 45Ca2+ from the medium, which was released by exposure to the ionophore A23187, to cyclic nucleotides (cyclic guanosine 5'-monophosphate [GMP] much greater than cyclic adenosine 3',5'-monophosphate [AMP]), and to the phosphodiesterase inhibitor, papaverine; and; they accumulated Ca2+ in an ATP-dependent manner when the cultured cells were permeabilized by digitonin extraction. ATP-dependent Ca2+ uptake was inhibited approximately 80% by ruthenium red and simulated by cyclic GMP much greater than cyclic AMP. Inositol 1,4,5-trisphosphate (IP3), which is thought to mediate the release of Ca2+ by the smooth muscle cell sarcoplasmic reticulum in vivo, released approximately 0.85 pmol Ca2+/million cells from the digitonin-extracted cells. IP3-dependent release occurred in the presence of ruthenium red and was not affected by cyclic GMP or cyclic AMP. These results indicate that smooth muscle from this human source can be grown successfully in cell culture and that the biochemical pathways that regulate tension in vivo may be perpetuated in vitro. Moreover, some of the clinical responses to drugs administered in situ for erectile dysfunction (e.g. papaverine) may be the result of altered cavernosal smooth muscle cell Ca2+ exchange and may be mediated by cyclic GMP.

Adult↗

Reversibility of cyclosporine-induced hypoandrogenism in rats.

In an attempt to determine whether the inhibition of the hypothalamic-pituitary-testicular axis induced by oral cyclosporine (CsA) is reversible, intact adult male rats were treated with 30 mg/kg oral CsA daily for 4 weeks, and then vehicle (orange juice) for the next 4 weeks. A second group of animals (control) was fed orange juice throughout the entire 8 weeks of the experiment. Serum testosterone (T) was decreased significantly (P less than 0.01) after 4 weeks of CsA treatment when compared with controls. After cessation of oral CsA for the next 4 weeks, there was no difference in serum T between the control and CsA-treated groups. Serum LH, intratesticular T, ventral prostate (VP) and seminal vesicle (SV) weights paralleled the serum T levels at 4 and 8 weeks--i.e., all values were decreased in the 4-week CsA-treated group when compared with controls, and these returned to normal at 8 weeks. Intratesticular 17 alpha-hydroxylase and 17,20-desmolase activities were significantly lower after 4 weeks of CsA treatment; following cessation of the CsA, these enzymatic values returned to normal within 4 weeks. These data demonstrate that at the duration of treatment and the dose studied, the CsA-induced inhibition of the hypothalamic-pituitary-testicular axis of the intact adult rat is completely reversible.

Androgens↗

Effect of cyclosporine on steroidogenesis in rat Leydig cells.

Cyclosporine induces hypoandrogenism in adult male rats. In order to assess whether this effect of CsA may be due to a direct inhibitory effect on Leydig cell function, CsA (0, 50, 500, and 5000 ng/ml) was added to a collagenase-dispersed mixed Leydig cell preparation and incubated with and without hCG (0, 0.1, 0.3, 1.0, 3.0, and 10.0 ng/ml). Testosterone (T) production, mitochondrial cholesterol side chain cleavage (CSCC) and microsomal 17,20-desmolase enzyme activities in Leydig cells were determined after 3 hr of incubation. In the absence of CsA, stimulation of T production was maximal (about 16-fold) with 1.0 ng/ml hCG. With 50 and 500 ng/ml CsA there were no changes in either the hCG-stimulated T levels or the two enzymatic activities. However, 5000 ng/ml CsA significantly (P less than 0.05) reduced the hCG (1 ng/ml)-stimulated T levels, CSCC and 17,20-desmolase activities. The high dosage of CsA (5000 ng/ml) also caused a significant decrease in cell viability (P less than 0.05) during the incubation period. These effects of CsA were not due to cremophor EL, the CsA vehicle. This in vitro data indicate that high dosages of CsA (greater than or equal to 5000 ng/ml) appear to have a cytotoxic effect on rat Leydig cells that results in a decrease in T production. However, lower doses of CsA (less than 500 ng/ml) do not have any direct inhibitory effect on the rat Leydig cells, suggesting that the hypoandrogenic effect of in vivo CsA in rats is not due to any direct effect on the testis.

Aldehyde-Lyases↗

Effects of gonadotropin-releasing hormone analogs on cis-platinum-induced spermatogenic damage.

In order to test the hypothesis that pretreatment with gonadotropin-releasing hormone (GnRH) analogs might ameliorate cytotoxic drug-induced testicular damage, mature male Wistar rats were pretreated for 2 weeks with a GnRH superactive agonist or a pure GnRH antagonist prior to, and for 1 week after, a 5 mg/kg intraperitoneal dose of cis-platinum. Despite inhibition of testicular function by both GnRH analogs prior to cis-platinum administration, there was no evidence of protection or enhanced recovery of spermatogenesis at 6 and 12 weeks after cis-platinum treatment, and spermatogenesis was significantly further depressed at both time-points by both GnRH agonist and antagonist pretreatment. This suggests that pretreatment with GnRH analogs in the rat does not protect spermatogenesis from cis-platinum-induced testicular damage within up to two spermatogenic cycles and that hypogonadism at the time of cytotoxic drug treatments may aggravate testicular damage.

Animals↗

Surgical and hormonal therapy for cryptorchidism: an overview.

The treatment of the undescended testis still engenders controversy on both sides of the Atlantic. To date, there is still no consensus on how to treat a child with an undescended testis. Some physicians advocate surgical therapy of all children whose testes are not located at the bottom of the scrotum whereas others feel that hormonal therapy should be tried initially on all such boys. The following attempts to provide an objective assessment of each of these two therapeutic modalities, highlighting the current controversies.

Chorionic Gonadotropin↗

Effects of cyclosporine on the hypothalamic-pituitary-gonadal axis in the male rat: mechanism of action.

In the intact adult male rat, cyclosporine (CsA) induces a significant decrease in serum testosterone (T), serum LH, and intratesticular T. To elucidate the mechanism of action of this CsA-induced hypogonadotropic hypogonadism, castrated male rats were treated with oral CsA (30 mg/kg.day) or vehicle alone, and serum LH was measured after 1, 2, and 4 weeks of treatment. Surprisingly, serum LH was higher in these CsA-treated castrated rats at 1, 2, and 4 weeks than in castrated controls. To provide insight into the cause of this increase in serum LH, a T implant (8 mm) was inserted (at week 5 of treatment) in both CsA-treated and control castrated animals, and serum LH was measured 1 week after insertion of the T implant. Serum LH levels decreased to control values after insertion of the T implant. Subsequently, two other groups of rats received 8-mm T implant at the time of castration and were then treated up to 4 weeks with either CsA or vehicle alone. Serum LH showed a significant decrease in these CsA- plus T-treated animals compared to the vehicle- plus T-treated animals. A GnRH stimulation test performed after 2 weeks of CsA/vehicle treatment showed a significant increase in serum LH in all the rats 30 min after GnRH administration (1, 10, 30, and 100 ng/100 g BW, ip), indicating a normal pituitary response. The increase in LH after exogenous GnRH treatment was more significant in CsA-treated intact rats than in the controls. There was no difference in creatinine clearance between intact and castrate T-treated rats regardless of whether they received CsA. These studies indicate that the hypogonadotropic hypogonadism induced by CsA in intact male rats is mediated through the hypothalamic-pituitary axis, primarily at its hypothalamus end, does not seem to be due to the nephrotoxicity of CsA, and is modulated by T and/or its metabolites.

Animals↗