Cyclosporine neoral in liver transplant recipients.
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Administration, Oral↗
Biomedical subjects
J Rochon
Publications and source records attributed to J Rochon.
Human mouse chimeric CD7 monoclonal antibody (SDZCHH380) for the prophylaxis of kidney transplant rejection.
mAb directed against CD7 have been shown to inhibit T cell proliferation in the allogeneic mixed lymphocyte reaction suggesting that CD7 may be an appropriate target for in vivo immunotherapy. We performed a prospective randomized clinical trial with a human-mouse chimeric CD7 mAb (SDZCHH380) and compared it with murine OKT3 for the prophylaxis of kidney transplant rejection. Twenty recipients of first cadaveric renal allografts were randomized to receive either SDZCHH380 or OKT3. SDZCHH380 was well tolerated. Rejection was delayed to day 35. No patients were sensitized to SDZCHH380. In contrast 7/10 OKT3 patients made anti-OKT3 antibodies. SDZCHH380 coated peripheral blood and lymph node T cells and, in contrast to OKT3, induced minimal release of IL-2, IL-6, TNF-alpha, and IFN-gamma. In addition, we showed that CD7-negative T cells mediated rejection in one of the SDZCHH380-treated patients. We conclude that the human-mouse chimeric CD7 mAb SDZCHH380 is well tolerated, is not immunogenic, and merits further study in the prophylaxis of transplant rejection.
Adolescent↗
An early 'clinical trial' as a teaching exercise: the Book of Daniel 1.1-15 (1.1-20).
This article discusses a very early clinical trial from the Old Testament. One of Daniel's and his companions' tribulations in Babylonia is explicated within the framework of the modern clinical trial. Even if many, or maybe even most, guidelines for good clinical trial practice are violated (it can even be argued that this is not really a clinical trial), a discussion of this biblico-historical episode in, for example, a problem-based course in (clinical) epidemiology or a course in the critical appraisal of the literature, can be a useful (and possibly entertaining) exercise.
Bible↗
Human mouse chimeric CD7 monoclonal antibody (SDZCHH380) for the prophylaxis of kidney transplant rejection.
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Animals↗
Analyzing the number of "rejection episodes" in renal transplant studies.
Transplantation has become the treatment of choice for many chronic and debilitating diseases. Generally, the primary endpoints in evaluating therapy are graft and patient survival time. However, an important secondary outcome is the number of "rejection episodes" experienced by study patients. This response has a distinctive statistical character. That is, it is a categorical variable since it assumes only a small number of integer values, but it is measured on a ratio-level scale since the ratio of any two values is scientifically meaningful. Historical methods for analyzing this endpoint, for example, t tests, logistic regression and Kaplan-Meier analysis, have failed to take these characteristics into account. In this study, we investigated statistical procedures for analyzing the number of rejection episodes arising during the first three months posttransplant. Data compiled by the Multiple Organ Retrieval and Exchange (MORE) of the Province of Ontario were used for this purpose. It was found that assumptions underlying normal distributional techniques were not satisfied by these data. An alternative model based on Poisson regression models was considered and was shown to provide an adequate fit.
Graft Rejection↗
Survival of cadaveric renal transplant grafts from young donors and in young recipients.
Evidence from multicenter registries has suggested that cadaveric renal graft survival is poorer when either the recipient or the donor is very young. We therefore analyzed our results from a single pediatric center. There was a significant correlation between greater recipient age and improved cadaveric graft (P = 0.002) and patient (P = 0.0009) survival. The age of the donor also appeared important, particularly in very young children, but became less so as donor age rose. Forty-four percent of recipients under 3 years old who received cadaveric kidneys from donors less than 4 years old lost their grafts as a result of renal thrombosis, ischemia, or technical problems, compared with only 3% of recipients over 9 years of age, whose grafts came from donors who were also over 9 years. The 1-year first cadaveric graft survival rates for these two age groups were 33% and 82% respectively. Our experience confirms the poor findings reported in very young recipients and with very young donors.
Adolescent↗
A statistical model for the "N-of-1" study.
The controlled clinical trial has largely replaced case-reports as the authoritative source of information concerning the efficacy of treatment. However, many situations arise in clinical practice where treatment decisions cannot be made on the basis of such studies. The definitive clinical trial may not have been performed, or the results from a particular study may not be applicable to a particular patient. Recently, "N-of-1" studies have been proposed for the experimental evaluation of therapy in a single patient. Multiple courses of active and placebo treatments are administered, and efficacy is determined by following the response measure over a period of time. The purpose of this paper is to present a statistical model appropriate for data arising from this design. The model provides for serial correlation among the response measures captured from the subject, and for heteroskedasticity across the treatment periods. ML estimation procedures are considered, and their properties are investigated. A scoring algorithm is described to iterate to the solution of the ML equations, and considerations for hypothesis testing are presented. The techniques are illustrated through an example.
Aged↗
First coronary heart disease event rates in relation to major risk factors: Quebec cardiovascular study.
The incidence of first coronary heart disease (CHD) events was evaluated prospectively in relation to the baseline measurements of systolic and diastolic blood pressure, serum cholesterol, smoking status and education in a cohort of 4576 Quebec men aged 35 to 64 and free from CHD at entry in 1974. From 1974 to 1986, 603 first CHD events were documented. The most frequent first manifestation was angina (6.7/1000 person-years) followed by nonfatal myocardial infarction (4.7/1000) and CHD death 2.2/1000). There was a positive relationship between the first CHD event and systolic (Z = 4.67) and diastolic (Z = 6.50) blood pressure. This relation was observed for angina, nonfatal myocardial infarction and CHD death. Serum cholesterol was also related to all events (Z = 4.99) but more specifically to angina and nonfatal myocardial infarction. Cigarette smoking was significantly related to first CHD manifestations. This relationship for specific CHD events was observed in men who smoked more than 20 cigarettes per day. Men who discontinued smoking one year before the study had a risk not different from those who never smoked. No relationship was observed between years of schooling and CHD events. Blood pressure, cholesterol and smoking constituted nearly two-thirds of the attributable risk of first CHD events.
Adult↗
Total and coronary heart disease mortality in relation to major risk factors--Quebec cardiovascular study.
The relationships of blood pressure, smoking, serum cholesterol and education levels on total and coronary artery disease (CAD) mortality were evaluated in 4576 Quebec men aged 35 to 64 years, free from overt CAD at entry and followed for 12 years. From January 1974 to January 1986, there were 417 deaths, 131 due to CAD. A progressive increase in total and CAD mortality was observed from quintile 3 to 5 for both systolic and diastolic blood pressure. In comparison to quintile 1, the adjusted relative risks of quintiles 4 and 5 for systolic blood pressure were significantly elevated (2 P less than 0.01), being 1.5 and 2.0 for total mortality, and 2.6 and 3.5 for CAD mortality, respectively. The relative risks of quintiles 4 and 5 for diastolic blood pressure were also significantly elevated (2 P less than 0.04), being 1.5 and 1.6 for total mortality and 1.9 and 2.7 for CAD mortality, respectively. In comparison to those who never smoked, the relative risks of smoking one to 20, and 21 and more cigarettes per day, were 2.1 (2 P less than 0.003) and 3.1 (2 P less than 0.0001) for overall mortality, and 2.2 (2 P less than 0.08) and 3.5 (2 P less than 0.002) for CAD mortality. Men who had discontinued smoking at least one year before the study, had a relative risk not different from those who had never smoked. Serum cholesterol and education levels were not significantly associated with total or CAD mortality.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Empirical classification of speech/language impairment in children. I. Identification of speech/language categories.
Cluster analysis was employed to classify speech/language impairment in a sample of 347 children 5 years of age. Based on scores on a variety of speech and language tests, four groups of children with similar linguistic profiles were identified. These groups were labeled high overall, low overall, poor auditory comprehension, and poor articulation. Differences among these groups according to cognitive, developmental, demographic, and audiometry variables were examined. The low overall group was most disadvantaged on all measures, the high overall group was most advantaged, and the poor articulation and poor auditory comprehension groups were intermediate. The implications of these findings for the development of a theory of the relationship between speech/language and psychiatric disorders are discussed.
Articulation Disorders↗
Empirical classification of speech/language impairment in children. II. Behavioral characteristics.
Behavioral symptomatology in 188 children, 5 years of age, classified according to four different speech/language profiles, is described. Information was collected from the teacher, parent, child self-report, and psychiatric interview. The results indicated that risk for psychiatric disorder, particularly ADHD, is greatest among children with general linguistic impairment. Specific deficits such as poor auditory comprehension or articulation problems were not consistently associated with behavioral disturbance. It is postulated that neurodevelopmental immaturity may be the common underlying antecedent of both linguistic impairment and psychiatric disorder.
Articulation Disorders↗
Spinal cord blood flow and systemic blood pressure after experimental spinal cord injury in rats.
We looked at the relation between systemic arterial blood pressure and recovery from spinal cord injury by inducing both hypertension and hypotension in 25 rats randomly allocated to five equal groups. The rats received no injury, a mild (2.3-g), or a severe (53.0-g) spinal cord injury lasting 1 minute. We used the hydrogen clearance technique to measure spinal cord blood flow at the injury site (T1) and at an adjacent site (C6). Mean systemic arterial blood pressure was either increased with adrenaline or decreased by phlebotomy in 20-mm-Hg intervals except for the severe-injury group, in which the posttraumatic pressure could only be increased with adrenaline. Spinal cord blood flow remained constant in the no-injury group between 81 and 180 mm Hg. After a mild injury, induced moderate hypertension (121-140 mm Hg) improved spinal cord blood flow significantly, whereas hypotension decreased it in a linear fashion. Severe injury caused a marked decrease in spinal cord blood flow and mean systemic arterial blood pressure. Even extreme hypertension (161-180 mm Hg) induced by adrenaline did not significantly increase spinal cord blood flow at T1 but caused hyperemia at C6 due to loss of autoregulation. In conclusion, normotension should be attempted, irrespective of the severity of spinal cord injury. Induced hypertension after severe spinal cord injury was not beneficial in improving spinal cord blood flow at the injury site while potentially increasing hemorrhage and edema.
Animals↗
Length of stay, short stay units and psychiatric emergency admissions.
Length of stay information was collected from 1,364 individuals over a one year period for five general hospitals in a major metropolitan area. The current set of data represents homogeneity in the nature of admissions and the type of facilities examined. Three of the hospitals operated short stay units. Significant differences in the total length of stay were observed according to age, sex and presence of psychosis but there were no unequivocal distinctions between short stay and conventional hospitals.
Adult↗
Effect of peak PRAs on the outcome of cadaver kidney transplants.
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Adult↗
The application of the GSK method to the determination of minimum sample sizes.
Grizzle, Starmer, and Koch (1969, Biometrics 25, 489-503) presented a unified approach for data analysis when the outcome variable is measured on a nominal or ordinal scale. The technique uses a weighted least squares methodology, and hypotheses are tested using asymptotic chi-square statistics. In this paper, we adapt these procedures to the problem of determining the minimum sample size required for an applied research effort, and use the noncentral versions of these chi-square statistics. The results are compared against several procedures widely used in the literature, and are found to concur well with these techniques. As well, some new situations are considered.
Clinical Trials as Topic↗
Maximum likelihood estimation for incomplete repeated-measures experiments under an ARMA covariance structure.
A stochastic model is presented for the analysis of incomplete repeated-measures experiments. The general linear model is used to relate the response measures to other variables which are thought to account for inherent variation; an autoregressive moving average (ARMA) time series representation is used to model disturbance terms. Maximum likelihood estimation procedures are considered, and the properties of these estimators are derived. It is concluded that while the assumptions underpinning the ARMA covariance models may be somewhat restrictive, they provide a useful inferential vehicle, particularly in the presence of missing values.
Analysis of Variance↗
The sensitized patient. A single center study.
1. In a 20-year period from 1966 to 1986, 650 renal transplants have been performed at the Toronto Western Hospital (University of Toronto). The 10-year actuarial patient survival is 62% and the actuarial graft survival is 35%. 2. A multivariant analysis using the Cox proportional hazard model indicated recipient age, donor source, graft number and time period were factors which independently influenced patient survival and that age and time period were variables which independently effected graft outcome. 3. Sensitization alone, using either peak or current PRA, did not significantly influence graft survival. Sensitization interacting with gender did affect graft survival, which was significantly lower in female patients with a high current PRA. Sensitization interacting with age produced different effects in the younger and older patients. The highly sensitized older patient has a better survival than the highly sensitized younger patient. However, for less sensitized patients the reverse was found; younger patients had a better survival than older patients. Also increasing levels of sensitization correlated with decreased survival in younger patients. 4. Predictive models based on the survivorship analysis of Kalbfleisch and Prentice were constructed to illustrate the impact of these variables on outcome.
Actuarial Analysis↗
Smoking, alcohol consumption, lipid and lipoprotein levels.
The lipid profiles of 1165 French Canadian men (aged 42 to 59 years) were studied and related to drinking and smoking habits. Alcohol consumption and smoking were closely related, smokers consuming twice as much alcohol as non-smokers. When relative body weight, total cholesterol, triglyceride and alcohol consumption were controlled in a covariate analysis, plasma levels of high density lipoprotein (HDL) cholesterol, HDL2 and HDL3 differed significantly between smokers, ex-smokers and nonsmokers. Ex-smokers had higher levels of HDL cholesterol than nonsmokers who had higher levels than smokers. The higher levels of HDL in ex-smokers could be explained by the confounding effects of alcohol intake. Alcohol users had significantly higher levels of HDL cholesterol, HDL2 and HDL3 than nondrinkers. Men who drank the equivalent of more than 3 ounces of absolute alcohol per week had significantly higher levels of HDL cholesterol and HDL3 than those who drank less than 3 ounces or did not drink at all. HDL2 levels were only significantly different between nondrinkers and those who consumed more than 3 ounces per week. These results show that smoking and alcohol have strong but opposing effects on HDL and its subfractions in middle-aged French Canadian men.
Adult↗