[Hepatic veno-occlusive disease associated to the use of azathioprine in a renal transplant recipient]. / Enfermedad venooclusiva hepática asociada a terapia con azatioprina en un paciente trasplantado renal.

We report a 30 years old male, recipient of a kidney allograft and treated with azathioprine, who eighteen days after transplantation had a clinically asymptomatic elevation of total bilirubin and alkaline phosphatases. Nineteen months later, he presented with mild ascites, with a total bilirubin of 3.5 mg/dl, alkaline phosphatases of 308 U/L (normal < 170 U/L) and a prothrombin time at 55% of control. A liver biopsy showed sinusoidal and perivenular fibrosis without inflammation, compatible with chronic venous obstruction. Hepatic veno-occlusive disease is an infrequent complication of azathioprine use.

[Chagas' disease in patients with renal transplantation]. / Enfermedad de Chagas en trasplantados renales.

After observing a fatal chagasic infection in a renal transplant recipient we investigated Chagas disease in 84 recipients of renal transplants. The indirect hemagglutination test was used for screening and xenodiagnosis followed in positive cases, along with ECG and gastrointestinal X ray series. Nine cases were detected (10%); parasites were found in the blood of 6 of them (66%). No patient had cardiac or gastrointestinal involvement. Patients with a positive serology were treated with nifurtimox (2) or benzonidazol (7); xenodiagnosis every 6 months up to 67 months remains negative in these patients. Blood transfusions are suspected as the mechanism for infection in these cases.

Ruptura de injertos renales:evolucion de 5 casos. / Rupture of renal grafts: course of 5 cases

Se revisan las etiologias, clinica y evolucion en 5 rupturas renales y 2 rerrupturas, en una serie de 60 trasplantes. Esta complicacion tiene, en nuestra serie, una incidencia del 8.3%, con um 100% de injertos perdidos y sin mortalidad, ya sea el tratamiento efectuado medico o quirurgico.Todas las rupturas de nuestra serie estan relacionadas con rechazos agudos severos.Recomendandose mejoria de las condiciones inmunologicas del binomio donante-receptor y restriccion en el uso de hemodialisis, por considerarse un factor predisponente

In vitro hypoxic cytotoxicity of nitroimidazoles: uptake and cell cycle phase specificity.

The hypoxic cytotoxicity of four different 2-nitroimidazoles of similar electron affinities but different lipophilicities was compared using EMT6/Ro mouse mammary tumor cells in exponential growth phase in severely (less than 20 ppm) hypoxic conditions. The relative cytotoxicities were misonidazole (MISO) = desmethylmisonidazole (9963) greater than SR-2508 much greater than SR-2555 indicating that the compounds with the lowest lipophilicity were less cytotoxic. The rates of uptake of these compounds were MISO greater than 9963 greater than SR-2508 = SR-2555. These data together with comparisons of the amounts of cell-associated compounds indicate that the similarity in toxicity of MISO and 9963 can be related to a general similarity in their pharmacokinetics, but that other unknown factors must be considered to explain the relative toxicity of SR-2508 and SR-2555. In other experiments, EMT6/Ro cells synchronized using centrifugal elutriation were most sensitive in hypoxia to MISO at the late G1--early S phase of the cell cycle. These data indicate the importance of considering cellular and subcellular distribution of these nitroimidazoles as well as possible cell cycle specificity for cytotoxicity in interpreting relative effectiveness of different compounds in responses of mixed populations of cells in cultures or tumors.

Effect of acute and chronic misonidazole administration on peripheral-nerve electrophysiology in mice.

I.p. administration at several dose levels over periods of up to 12 weeks, or continuous i.v. infusion of high doses of misonidazole (MISO) for 15 h, produced no significant change in peripheral nerve conduction velocity (NCV) and did not prevent the normal increase in NCV as the animals matured from 12 to 24 weeks of age. Peripheral NCV (sural nerve) was reduced in both MISO-treated and control mice with hind-limb tumour implants, presumably owing to physical pressure due to tumour growth. In addition, neither the medial nerves nor the tibial nerve in the normal limbs of the tumour-implanted, drug-treated animals showed any change. Consequently our earlier and present studies do not confirm the recent reports of changes in NCV following either acute or chronic MISO administration to mice.

The effect of misonidazole on some physiologic parameters in mice.

The physiologic effects of misonidazole (Ro-07-0582) were studied in BALB/cKa mice injected i.p. at 0.5 to 1.5 mg/g b.wt. A 2--4 degree C reduction of body core temperature was observed in unanesthetized mice: the duration and degree of effect were dependent on dose. Normal core temperatures were restored when the serum level of misonidazole had fallen to 0.5 microM (100 micrograms/ml). Misonidazole (1 mg/g) produced a rapid postinjectional drop of heart rate (40%), respiration (45%) and body core (4 degrees C) temperatures which gradually returned to preinjection values 6 to 8 hr later. In addition, misonidazole administration (1 mg/g) enhanced the overall effect on body temperature induced by hexobarbital anesthesia by a factor of approximately 3. These results are discussed in relation to the use of mouse model tumor systems to give an estimate of the magnitude of the cytotoxic effect of misonidazole expected in humans.

Peripheral electrophysiological parameters in mice treated with misonidazole.

The clinical use of the radiosensitizer misonidazole may be limited by the incidence of peripheral neuropathy reported following total doses in excess of 18 g. A recent report noted a decrease in nerve conduction velocity following a single i.p. injection of 1 mg/g misonidazole in mice. The present study was unable to confirm such changes when nerve conduction velocity measurements were made in situ or in isolated sural, tibial or median nerves of mice. Other electrophysiological parameters such as threshold, strength-duration curves, refractory time or the ability to carry high-frequency stimulation also showed no change. However, it was noted that a single administration of the radio-sensitizer produced a marked decrease in body temperature which persisted for at least 2 h after the elimination of the drug from the blood serum. The physiological response of reduction of body temperature may protect the mouse against the effect of the toxic chemical species involved in the induction of neurotoxicity.