Replacement therapy for inherited enzyme deficiency: liver orthotopic transplantation in Niemann-Pick disease type A.

Liver homotransplantation was attempted as replacement therapy in a 2-year-old patient with near total absence of sphingomyelinase activity of Niemann-Pick disease type A. Satisfactory function of the graft was observed until the death of the recipient from respiratory complication 2 years after transplantation. The clinical stigmata of the disease became less severe during the first 6 months after transplantation, with no further improvement thereafter. Sphingomyelinase activity was restored to near normal levels in serum, was present in cerebrospinal fluid and was maintained in the graft at normal or supranormal levels. No accumulation of sphingomyelin was observed in the transplanted organ as evaluated by histopathological and chromatographic studies. These findings support the interest of organ transplantation for long-term enzyme replacement in Niemann-Pick disease type A and similar lysosomal deficiencies.

Liver allograft. Its use in chronic active hepatitis with macronodular cirrhosis, hepatitis B surface antigen.

A patient suffering from chronic active hepatitis with macronodular cirrhosis, positive for hepatitis B surface antigen (HBsAg), was treated with an orthotopic liver allograft. The HBs antigenemia, as measured with several precipitation tests and by complement fixation, became negative after transplantation and remained so for about 2 1/2 months. During the interval, very low titers of the antigen were detectable by radioimmunoassay. At about three months after transplantation, she had an attack of acute hepatitis, at which time HBsAg became detectable by all tests. She recovered, but progressive liver disease developed during the remaining 1 1/2 years of her life. She died of disseminated nocardiosis and candidiasis with deteriorating hepatic function. The homograft at autopsy showed no evidence of rejection, but was the site of chronic active liver disease, although of a different pathologic pattern than that affecting her native liver. The differences in histology may reflect the influence of chronic immunosuppression on the features of chronic active hepatitis.

Alopecia, ascites, and incomplete regeneration after 85 to 90 per cent liver resection.

A nineteen year old female underwent 85 to 90 per cent partial hepatectomy to treat a minimal deviation hepatoma. Observations afterwards suggested that the limit of resection compatible with survival had been reached. She recovered perfect health after many months, although liver regeneration was not complete. Severe but eventually reversible alopecia and ascites developed postoperatively, undoubtedly as a complication of the massive hepatic resection.

Dialysis therapy among elderly patients; data from the Canadian Organ Replacement Register, 1981-1991.

Reports of clinical outcomes after commencement of dialysis treatment among elderly patients with end-stage renal disease (ESRD) are not been numerous. This paper describes the demographic and clinical characteristics of the elderly treated for ESRD in Canada using the Canadian Organ Replacement Register data. Comparisons with younger age groups are also presented. Analyses of data for the period 1981-1991 indicated that the elderly (65+) represent an expanding portion of all new ESRD patients in Canada. Distributions of dialysis modalities showed no major differences by age groups (45-54, 55-64, 65-75, 75+). However, the overall usage of intermittent peritoneal dialysis has decreased over time (from 17% of patients in 1981-83 to 7% in 1990-91). Deaths from social causes were slightly more frequent among the elderly (15.9% of all deaths among those aged 65+ vs 10% among those aged 45-64). Moreover, deaths from infections were more common among patients on dialysis for a longer period of time and more common among patients on peritoneal dialysis than among those on hemodialysis. Discontinuations of continuous ambulatory peritoneal dialysis (CAPD) because of the inability to cope increased with age. Patients with comorbid conditions were more likely to receive hemodialysis, and, as expected, the presence of these conditions increased with age and significantly reduced survival. Other determinants of survival included calendar period of registration, renal center size, and treatment modality. This paper illustrates the many changes over time in the elderly population treated for ESRD. Also of importance, however, is the elderly Canadian population with ESRD which is not presently treated.