The case history of a 56-year-old man is described who suffered from severe adrenocorticotrophic hormone (ACTH)-dependent Cushing's syndrome. The clinical course was complicated by simultaneous infections with Pneumocystis carinii, Staphylococcus aureus, Candida albicans, Aspergillus fumigatus and Herpes simplex, which proved to be fatal. A study of the literature shows that opportunistic infections in endogenous Cushing's syndrome are associated with severe cortisol excess and carry a high mortality. Opportunistic infections are most prevalent in the ectopic ACTH syndrome explained by the very high plasma cortisol concentrations in this condition. Infections with Aspergillus species, Cryptoccus neoformans, Pneumocystis carinii and Nocardia asteroides predominated. Cushing's syndrome with a very high plasma cortisol concentration causes a severe immunocompromized state. Prompt evaluation of the cause of the hypercortisolism, initiation of cortisol lowering therapy, primary prophylaxis for Pneumocystis carinii infection when plasma cortisol exceeds 2500 nmol L-1 and a search for concomitant infectious disease is recommended.

Conversion to a calcineurin inhibitor-free immunosuppressive regiment three months after renal transplantation improved allograft function, reduced the need of cardiovascular risk factor-controlling medication, and reduced the incidence of chronic allograft nephropathy.

ABSTRACT. Little is known regarding the composition of the interstitial extracellular matrix of kidney allografts with deteriorating function. Collagen I, III, and IV, the collagen IV α3 chain, and the laminin β2 chain were investigated in biopsies of allografted kidneys with chronic cyclosporine A nephrotoxicity (CsAT) (n = 17), chronic rejection (CR) (n = 12), or chronic allograft nephropathy (CAN) (n = 19). α-Smooth muscle actin expression was also examined. Normal native kidneys were used as control samples (n = 11). Biopsy samples were studied with routine light microscopy and immunostaining. The mean interstitial fibrosis scores were significantly higher for the CR and CAN groups, compared with the chronic CsAT group. The cortical tubulointerstitial areas of the CR and CAN groups, but not the chronic CsAT group, contained more collagen I than did normal control samples. Differences were noted even in biopsies with mild fibrosis. Accumulation of collagen III, IV, and IV α3 was increased in all patient groups. Collagen III accumulation was greater in the CR and CAN groups than in the chronic CsAT group. Receiver-operating characteristic curve analysis demonstrated that collagen I staining had the best discriminatory value in differentiating CR from chronic CsAT, with a sensitivity of 63% and a specificity of 94% at a cutoff value of 19%. Laminin β2 staining did not differentiate CR from CsAT. Increased α-smooth muscle actin staining did not differ among the three groups. It was concluded that, during chronic CsAT, collagen III and IV were preferentially accumulated in the tubulointerstitium. Early increases in the deposition of collagen I, with collagen III and IV, were more specific for CR. CR seems to elicit a more pronounced fibrotic response than does chronic CsAT. E-mail: RNR@euronet.nl

Renal laminin beta2 and TGF-beta mRNA levels can be used to differentiate between chronic rejection and chronic CsA toxicity in renal transplants. The method of mRNA quantification might be applicable as an additional diagnostic tool in clinical practice.

An elevated plasma homocysteine level may result from various environmental and genetic factors. Herediatary causes of severe hyperhomo-cysteinaemia are very rare and usually lead to disease in childhood or adolescence. Common pathology consists of early atherosclerotic vascular changes, arterioocclusive complications and venous thrombosis. Mildly elevated genetically determined plasma homocysteine levels are observed in 5% of the general population. In the last two decades research has shown mild hyperhomocysteinaemia to be linked to an increased risk of premature atherosclerosis, pregnancies complicated by neural tube defects and early pregnancy loss, and venous thrombosis. Homozygosity for thermolabile MTHFR deficiency has been identified as one important genetic factor, which expression is modified by dietary folate intake. Although mild hyperhomocysteinaemia can easily be treated by vitamin supplementation the beneficial effects of such treatment remains to be shown.