Donald C. Martin

COMPOSITE TISSUE (LIMB) ALLOGRAFTS IN RATS: II. INDEFINITE SURVIVAL USING LOW-DOSE CYCLOSPORINE

Cyclosporine has reawakened interest in transplantation of peripheral composite tissue allografts (CTA) of skin, muscle, bone, vessel, and nerves. The purpose of this study was to examine whether cyclosporine could produce indefinite survival of CTA. Two groups of LEW recipients of LBN limb transplants were given different long-term treatments of cyclosporine. Tolerance was achieved in many of the animals. Several possibilities for the mechanism of this tolerance are discussed.

Hypomagnesemia and renal magnesium wasting in renal transplant recipients receiving cyclosporine

Following the adoption and use of cyclosporine as the drug of choice in the management of renal allograft recipients, several cases of symptomatic hypomagnesemia were noted. These observations prompted the current prospective study of serum concentration and urinary excretion of magnesium in 27 renal transplant recipients treated with cyclosporine and prednisone. Relevant laboratory measurements were obtained shortly before and regularly after transplantation. The results were compared with those obtained in a group of 17 allograft recipients treated with azathioprine and prednisone. The cyclosporine-treated patients showed a significant reduction in the serum magnesium concentration and an inappropriately increased urinary excretion and fractional excretion of magnesium, suggesting renal magnesium wasting. The observed hypomagnesemia required magnesium supplementation in nearly all cyclosporine-treated patients. In contrast, azathioprine-treated patients showed normal serum magnesium concentrations and required no magnesium supplementation. In conclusion, administration of cyclosporine in renal allograft recipients appears to be commonly associated with renal magnesium wasting and hypomagnesemia. Therefore, it is recommended that serum levels of magnesium be monitored regularly in renal allograft recipients receiving cyclosporine and that magnesium supplementation be employed as needed to avoid magnesium depletion.

Composite tissue (limb) allografts in rats. III: Development of donor-host lymphoid chimeras in long-term survivors

Eight LEW rat recipients possessing long-term-surviving (206-701 days) LBN vascularized hind limb allografts (CTAs) were tested for donor-host lymphoid chimerism. The recipients received various cyclosporine (CsA) treatment protocols in order to induce indefinite CTA acceptance. Histological examination of long-term-surviving CTAs demonstrated normal-appearing bone marrow in the donor limb. Lymphocytes isolated from host hemopoietic tissues (peripheral blood and/or spleen) by ficoll-hypaque density gradient centrifugation were tested against LEW-anti-BN antisera. Comparisons were made to standard curves employing various known concentrations of LBN and LEW cell combinations. The level of lymphocyte agglutination (dependent variable) showed a significant (P less than 0.025-0.005) linear relationship to the concentration of LBN donor cells (independent variable) present. Lymphocyte suspensions isolated from long-term CTA host peripheral blood and/or spleen showed a mean of 19.7% (+/- 9.7-95% confidence interval) donor LBN mononuclear cells present. Thus, it appeared that lymphoid cells originated from, and/or were released from LBN donor bone marrow into the circulation, resulting in chimeric repopulation of hemopoietic tissues. The presence of donor immunocytes in these limb allograft recipients may have been beneficial, and thus could have helped contribute to the long-term CTA survival observed.

Composite tissue (limb) allografts in rats. I: Dose-dependent increase in survival with cyclosporine

The dose-response effect of cyclosporine on rat limb transplant prolongation was investigated across the LBN-to-LEW histocompatibility barrier. This composite tissue allograft model has been shown to represent a strong transplantation barrier. Median limb allograft survival times increased in a dose-dependent manner with low cyclosporine doses, and then reached a plateau at higher levels. The cyclosporine dose that produced half-maximal survival based on a 20-day treatment was only 3.7 mg/kg/day. Histopathology revealed that the rejection process was distinctly different in limb allografts treated with cyclosporine compared with noncyclosporine-treated controls. Rejection appeared to be delayed or partly arrested in certain areas of cyclosporine-treated limb allografts. These studies represent an initial step in laying the experimental foundation for clinical transplantation of composite tissue allografts using cyclosporine-induced immune suppression.

Acquired Renal Cystic Disease in Renal Transplant Recipients

End-stage kidneys are known to undergo cystic transformation in patients treated with long-term hemodialysis. Little has been published, however, on the occurrence of acquired renal cystic disease (ACD) in renal transplant recipients. The available clinical and histopathological data were gathered on 22 renal transplant recipients who had undergone either necropsy or nephrectomy. None of our patients exhibited cystic changes in their donor kidneys. However, 11 patients (50%) had ACD of the native kidneys while the remaining patients lacked ACD. The duration of dialysis prior to transplantation was significantly longer and the life of the functional transplant kidney was significantly shorter in the ACD group as compared to the noncystic group. The combined duration of ESRD (dialysis + transplantation), however, was comparable in the two groups. It thus appears that the presence of a functioning renal allograft somehow retards the evolution of cystic changes in the diseased native kidneys. 1 of the patients in the ACD group exhibited superimposed multifocal clear cell carcinoma of the affected kidney, while none of the patients in the noncystic group exhibited renal neoplasm.

Germinal Cell Tumors of the Testis After Orchiopexy

A review of the literature revealed 220 cases of germinal cell tumor of the testis that has occurred after orchiopexy. Of these cases 97 were accurately documented in regard to scrotal placement of the undescended testis and the subsequent tumor. Only 6 cases were reported after orchiopexy in children less than 10 years old. Since the number of patients at risk is unknown the possible protection of early orchiopexy against subsequent malignant degeneration cannot be established. The small number of cases reported after orchiopexy in children less than 10 years old is encouraging. The accumulated reports of germinal cell tumors of the testes after orchiopexy in patients between 10 and 20 years old militate against such a procedure in patients with a unilateral underscended testis.

Endometrioid adenosarcoma of the bladder arising from endometriosis.

Vesical endometriosis is an uncommon entity characterized by the deposition of benign, hyperplastic endometrial tissue in the bladder. To date, only about 160 cases have been reported in the world literature. More uncommon, however, are case reports of extrauterine malignancies arising from pre-existing endometriosis. We report a case of a large endometrial adenosarcoma in a patient who had undergone total abdominal hysterectomy and bilateral salpingo-oophorectomy 10 years previously for endometriosis. To our knowledge this malignancy has never been reported previously to involve the bladder. We review the pathological findings, possible mode of entry into the bladder and current concepts in its treatment.

The Effects of Testicular Trauma on Fertility in the Lewis Rat and Comparisons to Isoimmunized Recipients of Syngeneic Sperm

Adult male Lewis (LEW) rats were used to investigate the effects of unilateral testicular trauma on fertility. Comparisons were made between normal and experimental rats immunized with syngeneic sperm in Complete Freunds Adjuvant (CFA). Matings within the three groups yielded offspring to all normal males, no offspring to the immunized rats, and 27% (3/11) fertility in the trauma group (p less than 0.001). The contralateral testis demonstrated decreased volumes, various degrees of aspermatogenesis and smaller seminiferous tubular diameters, in both the trauma and immunized groups compared to the controls. Similar histopathologic findings of chronic granulomatous inflammation within contralateral testes in both the trauma and immunized groups suggested a common immune etiology for infertility via possible disruption of the blood-testis barrier.

Femoral Neuropathy: a Complication of Renal Transplantation

Femoral neuropathy occurred in 3 patients after renal transplantation. This appeared to be due to compression of the femoral nerve by medial and inferior blades of the self-retaining retractors used during renal transplantation surgery. The condition resulted in weakness of quadriceps muscles, loss of patellar reflex, and sensory deficit on the side of transplantation surgery. The rate of recovery from neurologic deficits appeared to depend on the level of transplant renal function.

The Use of Lipid Emulsion as an Intravesical Medium to Disperse Light in the Potential Treatment of Bladder Tumors

An obstacle to satisfactory treatment of early bladder cancer with hematoporphyrin derivative-photoradiation therapy is nonuniform illumination of the bladder mucosa. This study was done to determine the characteristics and attenuation of laser light passing through the dispersion medium. Bladder simulation was achieved with the use of 5 different sizes of round-bottom flasks. Intralipid was the dispersion medium. For each flask, 6 different concentrations of the dispersion medium were used. An Argon ion laser was used to stimulate a dye laser at 630 nm. The laser was directed toward the center of the flasks via a fiberoptic cable and energy concentration at 7 different angles was measured. We concluded that the optimal medium was a 1:100 dilution of Intralipid with water, which produced an almost uniform dispersion of light on the walls of the flask. There is a linear correlation between power as measured at the fiber tip and the amount of radiation detected on the walls of the flasks. After determining optimal concentration of medium, we calculated the amount of time needed for a desired energy (Joules/cm.2) to treat a tumor. This calculation was based on the size of the bladder and the power as measured at the fiber tip. The results indicate it is possible to treat the entire mucosa of the bladder with a uniform dose of photoradiation energy.