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Biomedical subjects

J Rochon

Publications and source records attributed to J Rochon.

At least 19 recordsLinked to original sources
PubMed2000

1,25-dihydroxyvitamin D3 synthetic analogs inhibit spontaneous metastases in a 1,2-dimethylhydrazine-induced colon carcinogenesis model.

In order to substantiate the role of vitamin D applicability for the prevention of colon cancer and its spontaneous metastases, the effect of 1,25-dihydroxyvitamin D3 and its synthetic analogs, 1, 25-dihydroxy-16,23Z-diene-26,27-hexafluoro-D3 (Ro 25-5317) and 1, 25-dihydroxy-16,23E-diene-26,27-hexafluoro-19-nor-D3 (Ro 25-9022), have been evaluated in a 1,2-dimethylhydrazine (DMH)-induced colon carcinogenesis model in Sprague-Dawley rats. In animals maintained on 2.75 nmol/kg 1,25-dihydroxyvitamin D3 diet no statistical difference was seen in tumor incidence when compared with control while in animals on 3.0 nmol/kg 1,25-dihydroxyvitamin D3 diet, the incidence of tumors was significantly lower. In animals maintained on 3.0 nmol/kg Ro 25-5317 diet also no statistical difference was seen in tumor incidence compared with control while in animals on 3. 5 nmol/kg Ro 25-5317 diet the incidence of tumors was significantly lower. The incidence of tumors in the group of animals maintained on 3.0 nmol/kg and 3.5 nmol/kg Ro 25-9022 was significantly lower, at 32.1% and 27.6% respectively, compared to control. In the two groups of animals maintained on the 1,25-dihydroxyvitamin D3 diet no significant difference in the incidence of metastasis was seen. In the group of animals maintained on 3.0 nmol/kg Ro 25-5317 diet only regional metastases were seen. However, no metastases developed in the rats on 3.5 nmol/kg Ro 25-5317 diet. After administration of 3.0 nmol/kg Ro 25-9022 diet, metastases developed in a significantly less number of animals while no metastases occurred in the rats maintained on the 3.5 nmol/kg Ro 25-9022 diet. The above studies will provide a scientific basis for the progression into further clinical trials in the treatment, and/or chemoprevention of human colorectal cancer.

1,2-Dimethylhydrazine↗
PubMed1998

Application of GEE procedures for sample size calculations in repeated measures experiments.

Derivation of the minimum sample size is an important consideration in an applied research effort. When the outcome is measured at a single time point, sample size procedures are well known and widely applied. The corresponding situation for longitudinal designs, however, is less well developed. In this paper, we adapt the generalized estimating equation (GEE) approach of Liang and Zeger to sample size calculations for discrete and continuous outcome variables. The non-central version of the Wald Chi 2 test is considered. We use the damped exponential family of correlation structures described in Muñoz et al. for the 'working' correlation matrix among the repeated measures. We present a table of minimum sample sizes for binary outcomes, and discuss extensions that account for unequal allocation, staggered entry and loss to follow-up.

Bias↗
PubMed1998

Randomized double-blind placebo-controlled trial of peptide T for HIV-associated cognitive impairment.

BACKGROUND: Cognitive impairment is a common consequence of human immunodeficiency virus (HIV) infection, and dementia is one of the diseases that defines the acquired immunodeficiency syndrome. Peptide T (d-ala-peptide-T-amide) has been reported to block the binding of gp120 to brain tissue and to protect neurons from the toxic effects of gp120 in vitro. In pilot studies, administration of peptide T to HIV-positive patients with cognitive impairment was associated with improvement in cognition and constitutional symptoms. OBJECTIVE: To determine whether the intranasal administration of peptide T would improve cognitive function of HIV-positive patients with cognitive impairment. PATIENTS AND METHODS: This was a 3-site, double-blind, placebo-controlled trial of peptide T given intranasally at a dosage of 2 mg 3 times a day for 6 months. Participants were HIV-seropositive persons with evidence of cognitive deficits on a screening test battery. Concomitant antiretroviral therapy was allowed. Randomization to the 2 study arms was balanced according to several stratification variables, such as CD4+ cell count, severity of cognitive impairment, and antiretroviral therapy at study entry. A comprehensive neuropsychological (NP) battery, which yielded 23 scores, was administered at baseline and the study end point. The primary outcome measure was a global NP score derived from the 23 standardized scores. The efficacy end point was the change in NP score at 6 months compared with baseline. Secondary efficacy measures were 7 cognitive domain scores and deficit scores of global and domain performance. The patients who completed the baseline and final NP evaluations (after at least 4 months in the randomized treatment arm) were included in the efficacy analyses. Additional analyses were conducted on subgroups of patients according to the CD4+ count and baseline NP deficit. The incidence of NP improvement in the 2 treatment arms was also compared. RESULTS: There was no statistically significant difference between the peptide T and placebo groups on the global NP change score, the individual domains, or the deficit scores. Because of an imbalance in the baseline CD4+ cell count between treatment arms, analyses were also adjusted for this variable. These CD4+-adjusted analyses suggested (P = .07; analysis of covariance [ANCOVA]) a greater improvement in the peptide T group. Subgroup analyses indicated a treatment effect for patients whose CD4 cell count was above 0.200 x 10(9)/L (200 cells/microL) at baseline. Moreover, peptide T treatment was associated with overall cognitive improvement in patients with baseline global deficit scores of at least 0.5, while overall deterioration was more common among the placebo group (P = .02; Mantel-Haenszel chi(2) test). CONCLUSIONS: Peptide T was not significantly different from placebo on the study primary end points. However, additional analyses indicated that peptide T may be associated with improved performance in the subgroup of patients with more evident cognitive impairment (ie, NP global deficit score > or = 0.5) or with relatively preserved immunological status (ie, CD4+ cell count > 0.200 x 10(9)/L).

AIDS Dementia Complex↗
PubMed1996

Analyzing bivariate repeated measures for discrete and continuous outcome variables.

A considerable body of literature has arisen over the past 15 years for analyzing univariate repeated measures data. However, it is rare in applied biomedical research for interest to be restricted to a single outcome measure. In this paper, we consider the case of bivariate repeated measures. We apply a generalized estimating equations (GEE) approach to relate each set of repeated measures to important explanatory variables. We then invoke the seemingly unrelated regression paradigm to combine these GEE models into an overall analysis framework. This approach provides a great deal of flexibility in modeling the relationships to fixed and time-dependent covariates for each set of outcome variables. Estimation and hypothesis testing issues are described and the methodology is illustrated with an example.

Analysis of Variance↗
PubMed1995

Methotrexate for the treatment of Crohn's disease. The North American Crohn's Study Group Investigators.

BACKGROUND: Although corticosteroids are highly effective in improving symptoms of Crohn's disease, they may have substantial toxicity. In some patients, attempts to discontinue corticosteroids are unsuccessful. METHODS: We conducted a double-blind, placebo-controlled multicenter study of weekly injections of methotrexate in patients who had chronically active Crohn's disease despite a minimum of three months of prednisone therapy. Patients were randomly assigned to treatment with intramuscular methotrexate (25 mg once weekly) or placebo for 16 weeks. The patients also received prednisone (20 mg once a day), which was tapered over 10 weeks unless their condition worsened. The primary outcome measure was clinical remission at the end of the 16-week trial. Remission was defined by the discontinuation of prednisone and a score of < or = 150 points on the Crohn's Disease Activity Index. RESULTS: A total of 141 patients were randomly assigned in a 2:1 ratio to methotrexate (94 patients) or placebo (47 patients). After 16 weeks, 37 patients (39.4 percent) were in clinical remission in the methotrexate group, as compared with 9 patients (19.1 percent) in the placebo group (P = 0.025; relative risk, 1.95; 95 percent confidence interval, 1.09 to 3.48). The patients in the methotrexate group received less prednisone overall than those in the placebo group (P = 0.026). The mean (+/- SE) score on the Crohn's Disease Activity Index after 16 weeks of treatment was significantly lower in the methotrexate group (162 +/- 12) than in the placebo group (204 +/- 17, P = 0.002). The changes in quality-of-life scores and serum orosomucoid concentrations were similar. In the methotrexate group, 16 patients (17 percent) withdrew from treatment because of adverse events (including asymptomatic elevation of serum aminotransferase in 7 and nausea in 6), as compared with 1 patient (2 percent) in the placebo group. CONCLUSIONS: In a group of patients with chronically active Crohn's disease, methotrexate was more effective than placebo in improving symptoms and reducing requirements for prednisone.

Adult↗
PubMed1995

Pharmacokinetics of a new oral formulation of cyclosporine in liver transplant recipients.

Trough concentrations of cyclosporine can be highly variable because of its poor bioavailability in current oral formulations, Sandimmune (SIM). Neoral (N-SIM) a new microemulsion of cyclosporine is more readily absorbed than SIM in healthy controls. The present study compared the pharmacokinetic profiles of SIM and N-SIM following orthotopic liver transplantation. In 16 patients with partial biliary diversion, 1 week after transplantation, the bioavailability and peak concentration of a single 300 mg dose of N-SIM were greater than SIM by 724% (p = 0.0019) and 800% (p = 0.0001), respectively. In 39 patients who were on stable doses of cyclosporine 1 month after transplantation, the bioavailability of N-SIM was higher than that of SIM under both fasting (+64%, p = 0.001) and fed (+37%, p = 0.004) conditions. Trough concentrations were similar for the two formulations. However, peak concentrations were higher for N-SIM in both fasting (+119%, p = 0.003) and fed (+53%, p = 0.003) patients. Also, time to peak was shorter for N-SIM in both fasting (-21%, p = 0.027) and fed (-59%, p = 0.0001) patients. The correlation between trough concentrations and bioavailability was greater for N-SIM than for SIM in fasted (r = 0.80, p = 0.0001 versus r = 0.75, p = 0.0001) and fed patients (r = 0.65; p = 0.002 versus r = 0.55; p = 0.012). We conclude that the rate of absorption and the bioavailability of N-SIM is significantly and consistently better than SIM and may, therefore, improve the therapeutic index of cyclosporine after liver transplantation.

Administration, Oral↗
PubMed1994

Low-dose cyclosporine for the treatment of Crohn's disease. The Canadian Crohn's Relapse Prevention Trial Investigators.

BACKGROUND: Long-term corticosteroid therapy for Crohn's disease is associated with important types of morbidity, such as osteoporosis. Safe and effective alternative treatments are required. Although a short-term benefit of cyclosporine in active Crohn's disease has been suggested, the long-term safety and efficacy of this treatment have not been established. METHODS: We conducted a randomized, double-blind, placebo-controlled evaluation of the effect of 18 months of low-dose cyclosporine treatment on the course of Crohn's disease. Adult patients whose disease had been active within the previous two years were randomly assigned to receive cyclosporine (151 patients) or placebo (154 patients) in addition to their usual therapy. Randomization was stratified according to center and score on the Crohn's Disease Activity Index (193 patients had scores of 150 or less, and 112 had scores greater than 150). The primary outcome measure was clinically important worsening of Crohn's disease, defined as a 100-point increase in the Crohn's Disease Activity Index from the patient's base-line value. Secondary outcomes were the use of prednisone and 5-amino-salicylates, mean score on the Crohn's Disease Activity Index and mean quality-of-life score, and the need for surgery. RESULTS: The condition of more patients worsened with cyclosporine than with placebo (91 of 151, or 60.3 percent, vs. 80 of 154, or 51.9 percent; P = 0.10). The median time to worsening of disease in patients receiving cyclosporine was 338 days, as compared with 492 days in patients receiving placebo (P = 0.25; relative risk, 1.22; 95 percent confidence interval, 0.86 to 1.72). Analyses of the mean Crohn's Disease Activity Index and quality-of-life scores and of the use of prednisone and 5-aminosalicylates also failed to demonstrate benefit. CONCLUSIONS: In our patient population, the addition of low-dose cyclosporine to conventional treatment for Crohn's disease did not improve symptoms or reduce requirements for other forms of therapy.

Adult↗
PubMed1994

Quality of life: a valid and reliable measure of therapeutic efficacy in the treatment of inflammatory bowel disease. Canadian Crohn's Relapse Prevention Trial Study Group.

BACKGROUND/AIMS: Quality of life (QOL), a subjective index of health perception and function, embraces physical, social, and emotional performance but has not had a prominent role in clinical trials of inflammatory bowel disease (IBD). To test the robustness of the Inflammatory Bowel Disease Questionnaire (IBDQ), a disease-specific QOL index, this study assessed its validity, reliability, and responsiveness during a multicenter trial. METHODS: Three hundred five patients with stable Crohn's disease received cyclosporin or placebo for 18 months. IBDQ and dimensional scores (bowel, social, systemic, and emotional) were correlated with disease activity (Crohn's disease activity index [CDAI] and Harvey-Bradshaw index). Concordance of IBDQ scores was tested in 280 stable subjects. Linear regression evaluated change in IBDQ scores over time. RESULTS: IBDQ scores correlated highly with CDAI (r = -0.67; P < 0.0001). The reliability coefficient for IBDQ score was 0.70 vs. 0.66 for CDAI and 0.55 for Harvey-Bradshaw index. Regression line slopes of IBDQ scores were significantly different in patients who deteriorated from those who remained stable ([b] < 0.15; P < 0.0001). QOL scores were lower in patients who required surgery. CONCLUSIONS: The IBDQ is a valid reliable assessment tool that reflects important changes in the health status of patients with IBD. The IBDQ is a robust measure of therapeutic efficacy and should be used in future clinical trials in IBD.

Adult↗
PubMed1993

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↗
PubMed1993

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↗
PubMed1992

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↗
PubMed1991

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↗
PubMed1990

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↗