Persistent allopeptide reactivity and epitope spreading in chronic rejection.
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Coronary Disease↗
Biomedical subjects
E Ho
Publications and source records attributed to E Ho.
Mechanism of liver allograft rejection: indirect allorecognition.
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Acute Disease↗
Characteristics of pregnant women who use ecstasy (3, 4-methylenedioxymethamphetamine).
To determine the characteristics of pregnant women who use Ecstasy (3,4-methylenedioxymethamphetamine, MDMA), and to identify reproductive risk factors associated with this group of women. Prospective, observational study. Pregnant women who have contacted the Motherisk Alcohol and Substance Use Helpline at The Hospital for Sick Children, in Toronto, about exposure to drugs, chemicals, infection or radiation. All inquiries from December 1998 to October 2000 concerning pregnant women who reported use of MDMA, and control cases of women not exposed to MDMA selected within the same week of the MDMA callers. Age, maternal demographics, pregnancy characteristics, patterns of alcohol, tobacco, and illicit drug use, psychological/emotional status, sexually transmitted disease, MDMA method and pattern of use, and adverse drug reactions after ingestion of MDMA. The 132 pregnant women who used MDMA were significantly younger (mean 23.2 vs. 31.2 years, P<.0001), and had more unplanned pregnancies compared to 122 pregnant nonusers (84.2% vs. 54.3%, P<.05). MDMA users were also more likely to be single (57.0% vs. 18.3%, P<.001), and to be White (82.2% vs. 56.0%, P<.05). Comparably more MDMA users smoked cigarettes (53.8% vs. 19.7%, P<.0001), drank alcohol (66.4% vs. 37.3%, P<.0001), and had significantly more episodes of binge drinking during pregnancy (mean 2.12 vs. 0.05, P<.001). Illicit drugs such as cocaine, marijuana, methamphetamine, ketamine, gamma-hydroxy butyrate, and psilocybin were used more frequently among the MDMA sample. Over a third of MDMA users reported psychiatric/emotional problems, including 6.5% with a clinically diagnosed condition that was being treated with medication and/or counseling. Pregnant women who use MDMA tend to be young, single, and report psychological morbidity, and have a clustering of risk factors that may compromise the pregnancy and fetus. Smoking, heavy alcohol intake, and polydrug use, combined with a higher than expected rate of unplanned pregnancies, increases the risk of fetal exposure to potentially harmful substances. It is important to account for the range of confounding risk factors among women who use MDMA in order to define possible direct effects of MDMA in pregnancy.
Adult↗
Neurologic complications of surgery for anterior shoulder instability.
Two-hundred eighty-two patients underwent anterior reconstruction for recurrent glenohumeral instability between 1981 and 1991. Twenty-three patients (8.2%) had a neurologic deficit after surgery. Seven had sensory disturbances only; 16 had sensorimotor neuropathies (8 having multiple deficits designated as a diffuse plexopathy and 8 having a more defined deficit in 1 or 2 cords or peripheral nerves). Complete resolution occurred in 18 of the 23 patients. Four patients had a residual deficit (1 patient was lost to follow-up). Three had persistent sensory disturbances; 1 had permanent biceps weakness. None of these patients underwent surgical exploration. Older age (P = .045) and a Bankart lesion (P = .029) were associated with a neurologic complication. At an average follow-up of 8.7 years, 252 patients responded to a questionnaire regarding shoulder outcome, including 20 of the 23 patients with nerve injuries. The difference in the median Rowe score of those with and without nerve injury was not significant (P = .072). Neurologic injuries after anterior shoulder surgery presumably arise as a result of traction. The prognosis for neurologic recovery is generally good. Neurologic injury did not interfere with the outcome of the stabilization procedure.
Adolescent↗
Relation of HLA antibodies and graft atherosclerosis in human cardiac allograft recipients.
Although cyclosporine has helped make heart transplantation a clinical reality, long-term survival remains limited by rejection and graft atherosclerosis. We have previously demonstrated the development of alloreactive lymphocytotoxic antibodies in baboon recipients of heterotopic heart transplants despite cyclosporine administration. The hypothesis of the present study is that cyclosporine-treated human heart transplant recipients are also capable of generating strong humoral immune responses that might adversely affect clinical outcome. Serial serum specimens from 240 heart transplant recipients were tested against a reference panel of 70 cells for anti-HLA lymphocytotoxic antibodies. Patients with serum panel reactive antibody levels greater than 10% were considered antibody producers, whereas those with serum panel reactive antibody levels less than 10% were considered nonproducers. To establish the time course of post-transplantation sensitization, we have tested anti-HLA antibodies in sequential sera at 3-month intervals after transplantation. The 4-year actuarial survival rate of those patients whose panel reactive antibody levels were greater than 10% during the first 6 months after transplantation was 70%, whereas the survival rate of patients whose levels were less than 10% during this time was 93%. The results were significantly different (p less than 0.01). Further heterogeneity among the patients was demonstrated by differential analysis of survival in patients who showed (1) panel reactive antibody levels less than 10% in any of the sera obtained during the first year after transplantation, (2) panel reactive antibody levels greater than 10% in sera obtained during the first 6 months but not thereafter, and (3) panel reactive antibody levels greater than 10% throughout the first year after transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
Babies with Down's syndrome.
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Down Syndrome↗
Additive value of immunologic monitoring to histologic grading of heart allograft biopsy specimens: implications for therapy.
BACKGROUND: Currently the sole method available for diagnosis of heart allograft rejection is endomyocardial biopsy. Although this procedure offers important criteria for treatment, it cannot always discriminate between mild episodes of rejection which might be self-limiting and forms which may progress. In an effort to monitor rejection, we have implemented a cellular monitoring strategy aimed at identifying episodes of rejection in biopsy specimens which may evolve into higher grades of rejection. The lymphocyte growth assay is based on the capacity of interleukin-2 receptor-positive T cells to expand in the presence of interleukin-2 and antigen provided by the biopsy fragment. In this study we investigated whether a positive lymphocyte growth assay correlated with and was predictive of subsequent histologic allograft rejection and the development of anti-human leukocyte antigen antibodies. METHODS: Lymphocyte growth assay was performed on 437 biopsy specimens from 76 patients. Patients with mild allograft rejection defined as grade 2 rejection were randomized to treatment according to the results of the lymphocyte growth assay. Anti-human leukocyte antigen antibodies was also measured monthly. Cells grown from the biopsy specimens were tested against the donor cells and allopeptides derived from the donor human leukocyte antigen-DR. RESULTS: A highly significant correlation was observed between the histologic grade of rejection and growth of graft infiltrating cells (p < 0.0001). Lymphocyte growth occurred in 10% of grade 0 versus 60% of grade 3A biopsy specimens. Only 4% of histologically negative cases with negative lymphocyte growth assay progressed to rejection in the next month. In the randomized study in which treatment was based on the lymphocyte growth assay results, progressive rejection occurred in three of four cases with positive lymphocyte growth assay versus only 1 of 11 with a negative lymphocyte growth assay (p < 0.001). A highly significant correlation was found between a positive lymphocyte growth assay and subsequent development of antihuman leukocyte antigen antibodies (p < 0.0006). This finding indicates that cellular rejection evidenced by lymphocyte growth assay ultimately results in humoral antihuman leukocyte antigen antibody mediated rejection. Limiting dilution analysis showed that although the direct recognition pathway prevails in early rejection, cells participating in the indirect pathway also proliferate vigorously in the graft during rejection. CONCLUSIONS: Monitoring of rejection with lymphocyte growth assay is a simple method which provides prognostic information on the outcome of cardiac allografts. Lymphocyte growth assay correlates with histologic rejection and is predictive of future histologic rejection episodes. Lymphocyte growth assay also predicts subsequent development of antihuman leukocyte antigen antibodies and thus may provide a useful method for ascertaining the onset of chronic rejection.
Adult↗