PubMed HealthSearch

Biomedical subjects

W Wall

Publications and source records attributed to W Wall.

At least 19 recordsLinked to original sources

Arteritis and increased intracellular calcium as a possible mechanism for tacrolimus-related cardiac toxicity in a pediatric transplant recipient.

We recently reported partially to wholly reversible hypertrophic cardiomyopathy, including severe hypertrophic obstructive cardiomyopathy, as a side effect in pediatric transplant recipients receiving tacrolimus immunosuppression. This seemed to be dose related. We describe a pediatric patient receiving tacrolimus who died 3 weeks after liver/bowel transplantation. Postmortem findings revealed arteritis of cardiac arteries and extensive calcification of cardiac tissue suggesting a possible mechanism of tacrolimus cardiac toxicity. This is consistent with recent reports of tacrolimus increasing calcium release into the sarcoplasmic reticulum of cardiac and striated muscle.

Arteritis

An analysis of late deaths after liver transplantation.

Late deaths (after more than 1 year) after liver transplantation were analyzed in a series of 464 consecutive patients who received liver grafts between 1982 and 1993. Recipients who survived the first posttransplant year (n = 365) had actuarial 5- and 10-year survival rates of 92% and 84%, respectively. Thirty-five patients died between 1.1 and 7.6 years after transplantation (mean, 3.2 +/- 1.9 years). The most common causes of death were related to immunosuppression (40%), namely, chronic rejection, opportunistic infection, and lymphoma. The second most common causes of death were related to the primary disease for which liver transplantation was performed (34.3%), mainly recurrence of hepatobiliary malignancy and hepatitis B. Eight patients (22.9%) died of unrelated and unpredicted causes, most commonly of cardiovascular disease. Although the survival of liver recipients who live beyond the first posttransplant year is excellent, control of rejection and the consequences of chronic immunosuppression are continual threats. Modification of immunosuppression may help in decreasing the mortality of long-term survivors. In addition, better selection of recipients and effective adjuvant therapies (antiviral and antineoplastic) are needed in patients in whom the primary liver disease is notorious for recurrence.

Adolescent

Small bowel transplantation. A life-saving option for selected patients with intestinal failure.

Thirty-seven patients were listed for small bowel transplantation; 16 were transplanted and 15 died while waiting for a donor. Cyclosporine (N = 6) or tacrolimus (N = 10) were used for immune suppression. Graft rejection rates were lower in the combined liver/small bowel grafts than the isolated intestinal transplants (1/7 vs 5/7; P < 0.01) All of the cyclosporine group have died; the median survival was 25.7 months with two patients living more than five years. The tacrolimus group had fewer infections and a shorter hospital stay. All but two are alive with a median survival of 13 months. Seven of eight long-term survivors are off intravenous feedings. We conclude that small bowel transplantation is a life-saving option for patients with intestinal failure who cannot be maintained on total parenteral nutrition.

Adolescent

Hypertrophic cardiomyopathy associated with tacrolimus in paediatric transplant patients.

Reported side-effects of tacrolimus, a potent immunosuppressive agent, have not included cardiotoxicity. We describe 5 consecutive paediatric transplant recipients (3 small bowel with or without liver and 2 liver) who received tacrolimus. 2 developed congestive heart failure and hypertrophic obstructive cardiomyopathy which resolved after changing to cyclosporin. In the other 3 patients the cardiomyopathy regressed or improved with a lower dose of tacrolimus or after stopping the drug.

Blood Pressure

The OKT3 Antibody Response Study: a multicentre study of human anti-mouse antibody (HAMA) production following OKT3 use in solid organ transplantation.

Human anti-murine antibody titres following patient exposure to the monoclonal antibody Orthoclone OKT3 (muromonab-CD3) are determined by laboratories using diverse analytical methods which are not standardized and whose concordance is not established. A multicentre study group therefore compared testing for IgG anti-OKT3 antibody among seven laboratories. A set of 270 sera was obtained from 30 heart, 30 kidney and 30 liver transplant recipients with no previous exposure to OKT3 who were receiving OKT3 for induction immunosuppression. Sera were collected from each patient prior to and at 24 +/- 2 days and 31 +/- 2 days following initial OKT3 exposure. Identical aliquots of all 270 sera were tested for IgG anti-OKT3 antibody by each laboratory. In addition, the limit of detection of each laboratory's method was estimated by titration of an affinity-purified IgG anti-OKT3 reference material of known concentration. Anti-OKT3 antibody formation differed greatly among the three organ groups. Cardiac patients demonstrated the least sensitization and almost exclusively lower titres, while kidney recipients had more frequent and higher titre antibody formation. Liver recipients yielded the highest sensitization rate and the most frequent high titre sera. Importantly, the seven laboratories differed widely in the number of pretreatment sera reported as positive (ranging from 0% to 41% among laboratories), the number of post-OKT3 sera reported as positive (17-63%), the number of post-OKT3 samples with titre > or = 1000 (2-31%), and the number of patients sensitized 19-69%). Concordance among laboratories was highly variable, with interlaboratory agreement ranging from 38% to 83% on the sample titres assigned to 180 post-OKT3 sera. Many of the discordant results were consistent with differences in the limit of detection of the analytical methods, which ranged from 0.19 microgram/ml to > or = 15 micrograms/ml, a nearly 100-fold difference among laboratories. This study demonstrated the presence of both good concordance and significant discordance among laboratories in determining human anti-mouse antibody titres, and demonstrated that common titre categories (100, 1000, 10,000) were not equivalent among laboratories. The level of concordance among methods should be considered when comparing anti-OKT3 antibody results from different centres and their correlation with clinical events. Universal comparative testing, patterned after proficiency testing programmes, is needed to assess differences among laboratories and to bring uniformity and a sound interpretative basis to this field of testing.

Adult