Clinical aspects and perspectives in islet xenotransplantation.

In 1990-1993, eight diabetic renal transplant patients had porcine fetal islets injected intraportally at Huddinge Hospital in Stockholm. Four of the patients had evidence of xenograft function reflected in the excretion of small amounts of porcine C-peptide. Two patients had the porcine fetal islets placed under the capsule of a simultaneously transplanted kidney. In one of these patients, a graft biopsy specimen taken 3 weeks after transplantation revealed morphologically intact epithelial cells staining positively for insulin and glucagon. The insulin production was in all instances insufficient to affect the patient's insulin requirements. All patients formed specific xenoantibodies (mostly anti-Gal); presumably, most of the xenoislets were destroyed by rejection. On follow-up studies carried out 6-8 years after xenotransplantation, most patients still had higher-than-pretransplant levels of xenoantibodies. There was no evidence of transmission of porcine endogeneous retroviruses to the patients. All patients expressed a positive attitude toward the use of animal tissue for treatment of disease, and none of the patients regretted participating in the trial. Cell transplantation is leading the way at present for clinical xenotransplantation. The finding that complement inhibition protects intraportally injected porcine islets from an injurious incompatibility reaction holds promise for future clinical application. A similar protective effect might be achievable with the use of islets from transgenic pigs expressing human complement receptors.

Human immunodeficiency virus type 1 enhances intracellular growth of Mycobacterium avium in human macrophages.

Disseminated Mycobacterium avium infections are common in patients with AIDS and result in a reduced life expectancy. Human monocytes/macrophages are important target cells for both human immunodeficiency virus (HIV) and M. avium. We have studied the interaction in vitro of M. avium and HIV type 1 (HIV-1) in human macrophages. Human monocytes isolated from the peripheral blood of healthy individuals were infected with HIV-1, M. avium, or both. The intracellular growth of M. avium and the replication of HIV-1 were monitored for up to 5 weeks. Intracellular mycobacterial growth was seen in all M. avium infected cell cultures and was paralleled by increased production of interleukin 1 alpha and beta. Preinfection of the macrophages with HIV-1 reduced the interleukin 1 production and accelerated the intracellular growth of M. avium. These findings may explain in part the impaired control of mycobacterial infections seen with patients with AIDS.

Susceptibility of mycobacteria to fusidic acid.

Fusidic acid was shown to be effective in vitro against 30 clinical isolates of Mycobacterium tuberculosis at concentrations of 32-64 mg/l, concentrations which are readily achieved in serum. All but one of 17 Mycobacterium avium complex strains were resistant to fusidic acid at concentrations up to 64 mg/l. However, synergistic effects were shown for 11 of the 17 strains when fusidic acid was combined with ethambutol. Five of the strains were fully susceptible to the combination of fusidic acid (64 mg/l) and ethambutol (4 mg/l). It is suggested that fusidic acid should be evaluated clinically as a potential supplementary drug for treatment of mycobacterial infections.