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When cyclosporine was introduced as an immunosuppressive agent, there was concern that cyclosporine could be detrimental to long-term renal allograft function and survival. In response to this concern, we report a 5-year followup of 200 consecutive renal transplant recipients among whom initial immunosuppression and risk factors were similar except for the substitution of cyclosporine for azathioprine in the second 100 recipients. The azathioprine and cyclosporine groups had similar 1-year (89% versus 91%) and 5-year (74% versus 80%) patient survival rates. Cyclosporine treated patients had superior 1-year (83% versus 58%) and 5-year (61% versus 29%) graft survival rates. At the 5-year interval, cyclosporine treated grafts had an elevated, yet stable, mean serum creatinine level compared to azathioprine treated grafts. Despite ongoing mild renal dysfunction in cyclosporine treated grafts, cyclosporine does not induce an inexorable decrease in graft function and continues to provide long-term graft survival superior to azathioprine.

Iliac artery-ureteral fistulas are uncommon, with less than 15 cases described in the literature. Ureterocolic fistulas have been described even less frequently. We report the first case of synchronous right ilioureteral and left ureterosigmoid fistulas associated with indwelling ureteral stents. The patient presented with massive sentinel gross hematuria, urosepsis and chronic anemia.

This study evaluated the long term effects of unilateral torsion of the spermatic cord on the contralateral testis of guinea pigs, employing both fine structural and quantitative studies. Young, adult Hartley strain guinea pigs were divided into six experimental groups (12 animals per group). The first three groups consisted of 36 animals in which unilateral torsion was surgically induced. In group I (torsion maintained), unilateral torsion of the spermatic cord was maintained until the day of sacrifice; in group II (torsion and untwist), torsion of the spermatic cord was maintained for 8 to 12 hours, then the spermatic cord was untwisted and the testis was retained until the day of sacrifice. In group III (torsion and orchiectomy), testes were removed after 8 to 12 hours of spermatic cord torsion. The second three groups consisted of 36 animals: group IV (unilateral orchiectomy), group V (unilateral sham operation), and group VI (pentobarbital injection alone), which served as controls. One half of the animals from each group were killed after 4 months and the other half were killed after 8 months. The most frequently observed histologic changes in the contralateral testes of the experimental animals were focal disorganization and exfoliation of immature germ cells into the lumen. Severe damage, with almost complete absence of germ cells, was noted only in an occasional tubule. Quantitative evaluation of the germ cells of the contralateral testis revealed significant loss of germ cells in groups I, II, and III after 4 months, and in groups I and II after 8 months.(ABSTRACT TRUNCATED AT 250 WORDS)

Twenty-eight Hartley strain guinea pigs were divided into three groups. Group I animals had their exteriorized testes torsed for a variable period of time until a bluish black color was maintained after detorsion. Group II and III animals served as controls. Testicular hormone function was estimated by analysis of accessory sex gland weights and citric acid and fructose content. Spermatogenesis was assessed by testicular histology and sorbitol dehydrogenase activity and epididymal sperm number and motility. No apparent effect on either spermatogenic or hormonal function of the guinea pig testis resulted from the torsion of the spermatic cord to the degree and length of time described.

An ultrastructural stereological analysis of Leydig cells of the guinea pig testis was carried out following surgically induced testicular torsion. Morphometric analyses of the Leydig cells of the experimental group of animals revealed an increase in the nuclear and mitochondrial volume and a decrease in the lipid volume, in comparison to those in the Leydig cells of the control group of animals. We believe that these changes in the Leydig cells of the experimental group of animals are indicative of cellular hypertrophy. The possible mechanisms of the Leydig cell hypertrophy in the guinea pig testis following the induction of spermatic cord torsion are discussed.

Quantitative analysis of human seminiferous epithelium was carried out using an improved method of glutaraldehyde and osmium fixation with plastic embedding. Part of each biopsy specimen was fixed in Bouin's fixative and embedded in paraffin for comparison. Epon embedded tissue had very little artifactual damage compared with paraffin embedded tissue sections. The germ cell to Sertoli cell ratios were determined by counting the various germ cells per "unit" tubular area. Data obtained by this method reflect a remarkable stability of Sertoli cell number and germ cell-Sertoli cell ratios both between biopsies from different individuals and between biopsies from right and left testes from the same individual. Agreement between the present results and those of earlier studies based on paraffin embedded testicular specimens supports the validity of this method of germ cell quantitation of human testicular biopsy samples.

Torsion of the spermatic cord is not uncommon among young men. Various abnormalities in the histology of the contralateral testis have been reported due to unilateral torsion of the spermatic cord. We quantitatively estimated the germ cells from three groups of men: normal individual (Group I), men with unilateral torsion of short duration (Group II), and men with unilateral torsion of long duration or some other condition such as varicocele or intermittent torsion to the contralateral testis (Group III). No significant difference in the number of spermatogonia, spermatocytes, and spermatids of Groups I and II patients was observed. This observation indicates that there was no pre-existing morphophysiologic defect in the testis of Group II patients. Severe damage in the contralateral testis was noted in Group III patients. This indicates that if a damaged testis is retained in the body for a long time, the contralateral testis may be affected. Contralateral testis may also be affected by intermittent torsion or varicocele.

Most renal transplant centers report an increase in graft survival when cyclosporine is used as a primary immunosuppressant. We report the outcome of 200 consecutive cadaver renal transplant recipients among whom initial immunosuppression and risk factors were similar except for the substitution of cyclosporine for azathioprine in the second 100 recipients. Azathioprine-treated recipients had significantly increased (p less than 0.05) mean hospital stays (31.9 versus 18.3 days), incidence of first rejection episodes (85 versus 31) and methylprednisolone dose (3.38 versus 0.06 gm. per patient). Cyclosporine-treated recipients had a significantly higher 1-year mean serum creatinine level (1.85 versus 1.56 mg. per dl.) and 1-year actual graft survival (83 versus 58 per cent). Despite mild nephrotoxicity, cyclosporine is superior to azathioprine as a primary immunosuppressant in cadaver kidney transplantation.

In our previous studies, we reported that short-term unilateral spermatic cord torsion had no adverse effect on the germ cells and the Sertoli cell in the contralateral testis of men. As an extension of our earlier investigations on the testicular pathophysiology in humans after unilateral spermatic cord torsion, the present study was undertaken to assess the Leydig cell function employing both fine structural and morphometric analysis in patients with short-term spermatic cord torsion. Bilateral testicular biopsy samples obtained from 4 men (15-19 years) with short-term unilateral torsion of the spermatic cord and from a control group of 6 men (15-40 years) were used in the present investigation. No appreciable difference in the Leydig morphology was noted between the biopsy samples from control and the contralateral testes. This was substantiated by morphometric analysis. The present study clearly indicates that patients with unilateral torsion of the spermatic cord may not essentially have bilateral testicular abnormalities, as suggested by the previous investigators. This report, thus lends further support to our earlier contention that alteration in microcirculation is quite likely the earliest and possibly the most significant contributor to the contralateral testicular damage in man after ipsilateral spermatic cord torsion.

This study reports on the stagnation of blood within the microcirculatory vessels of the testes of patients with varicocele. Both fine structural and quantitative studies were carried out on testicular biopsies from 14 men with varicocele and a control group of three men. Arterioles, capillaries, and venules were completely filled with blood in all affected testes. Enlarged pores were also noticed between the endothelial cells of these affected vessels. Lumen diameters of the arterioles were significantly decreased in the affected testis compared to controls. No change in the overall diameter of the arterioles and venules was noted. Significant thickening of the limiting membrane was also noted in the affected testis. It was concluded that the stagnation of blood in the microcirculatory vessels may cause local hypoxia and ischemia, which lead to spermatogenic disorders.

The short term effects of bilateral vasectomy on the testis and the accessory sex glands of the guinea pig were compared with the effects of sham operation and unilateral vasectomy at 3, 5, 7, and 9 weeks after operation. The testis weights, sorbitol dehydrogenase activity, histology, epididymal sperm number, and motility were recorded. Accessory sex glands were weighed and chemically analyzed for fructose and citric acid content. The citric acid concentration of the dorsolateral prostate of the bilateral vasectomy group was significantly higher than concentrations in sham-operated and unilateral vasectomy groups at 3 weeks only. This may indicate transient hormonal derangement as a result of vasectomy. No significant differences were noted between testes of vasectomy and sham-operated groups. The unligated side testes of the unilateral vasectomy group were different from the testes of vasectomy and sham-operated groups. We conclude that interruption and ligation of the vas deferens itself has no effect on the testis of the guinea pig. Furthermore, all vasectomy experiments should include sham-operated controls.

The role of renal biopsy in 46 patients with end stage renal failure was assessed. Renal tissue was obtained by open renal biopsy in 24 patients, by needle biopsy in 5, and at bilateral nephrectomy in 17. In 4 patients the renal biopsy specimens showed advanced changes that could only be diagnosed as "end stage kidney". In 42 patients (91 per cent), a precise renal diagnosis was made. In 20 patients (43 per cent) the prebiopsy clinical impression differed from the histologic diagnosis. In the 29 patients undergoing renal biopsy, minor postoperative morbidity occurred in 5. We conclude that a renal biopsy in patients with end stage renal failure will result in a change in clinical diagnosis in a significant number of patients and can be performed with low morbidity.

Bilateral testicular biopsies from four men with a short duration (3 hours 10 minutes to 4 hours 30 minutes) of unilateral spermatic cord torsion and testicular biopsies from six men with irreversible brain death were used for the present investigation. Extensive light and electron microscopic studies and quantitative analyses of all biopsy materials were performed. The torsioned testes revealed variable degrees of damage to the seminiferous tubules, including germ cell disorganization and sloughing of immature germ cells. Ninety-five percent of the blood vessels from the biopsied tissue specimens were clogged with blood cells. The seminiferous tubules of the contralateral testis had normal germ cell arrangements and counts. However, 88% of the microvessels from the tissue biopsied from the contralateral testes were packed with blood cells, whereas only 10% of the blood vessels in the control biopsy specimen were clogged with blood cells. At the electron microscopic level, fewer tight junctions and enlarged pores were found between the endothelial cells of the affected vessels, and microvilli were completely absent from these endothelial cells. The clogging caused by blood cells in the affected vessels was so severe that no space was found between the membrane of the endothelial cell and the membrane of the blood cells. It has been suggested that local clogging by blood is responsible for the initiation of degenerative changes in the testes of men with unilateral torsion of the spermatic cord.

Unilateral torsion of the spermatic cord was surgically induced in 24 Hartley strain guinea pigs. Groups of six animals were sacrificed 4, 8, 12, and 16 months after the surgery and testes were excised. Nine animals has severely damaged testes. Extensive study on the Sertoli cells of each of these nine animals was carried out after testicular tissues were processed for electron microscopy following the usual procedure. The majority of the affected seminiferous tubules contained a single layer of Sertoli cells without any differentiating germ cells. The Sertoli cells were vacuolated and contained highly lobulated nuclei. Each nucleus contained a nucleolus. The Sertoli cells contained an elaborate annulate lamellae system. The membranous portion of the annulate lamellae was associated with the rough and smooth endoplasmic reticulum. Close association of the annulate lamellae with the lysosomes and lipid droplets was found to be a consistent feature. Although it was not possible for us to predict the functional significance of these annulate lamellae, the present investigation clearly established for the first time, the presence of an annulate lamellae system in the Sertoli cell of a rodent species.