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Biomedical subjects

P Duquette

Publications and source records attributed to P Duquette.

At least 19 recordsLinked to original sources

Drug abuse as a risk factor of multiple sclerosis: case-control analysis and a study of heterogeneity.

The etiology of multiple sclerosis (MS) remains unknown despite considerable research involving a number of disciplines for many decades. Cluster analysis was used to disentangle the possible heterogeneity of MS, based on clinical characteristics of 108 subjects. Further on, a case-control study was conducted within each subgroup found with the cluster analysis, to test with more validity environmental risk factors, such as alcohol, tobacco, medication and drug abuse. The controls with a rheumatoid arthritis condition were matched to the cases on age, gender and same postdiagnostic period and were recruited from the same hospital. Three main groups of MS subjects were obtained from the cluster analysis, distinguished by the gender, the presence or not of family history and the degree of severity of their physical disability. The results showed that drug abuse was the only risk factor with a statistically significant odds ratio for overall and for the unique female group without familial history of MS.

Adult

The increased susceptibility of women to multiple sclerosis.

Many diseases with an auto-immune etiology have a skewed sex distribution. In the majority of instances, women are affected more frequently than men. A review of population studies demonstrates that the preponderance of women in multiple sclerosis (MS) is almost constant. We show that this preponderance is further increased in early as well as in late-onset cases, in familial cases as well as in MS twin pairs and that the HLA-DR2 allele, which has been associated with MS in Caucasian populations, is significantly more frequent in women than in men with MS. "Rules" have been established for multifactorial diseases; MS contravenes most of those rules. The skewed sex distribution in MS could be attributed to the known hormonal and gender influences on the immune response, as well as to genetic influences.

Diseases in Twins

Immunoregulatory properties of T-cell lines derived from the systemic and intrathecal compartments: a phenotypic and functional study.

To determine whether immune regulation can differ within the intrathecal and systemic compartments, we compared phenotypic markers and functional properties of in vitro anti-CD3 monoclonal antibody-stimulated, interleukin 2-expanded lymphoid cell lines simultaneously derived from peripheral blood and cerebrospinal fluid of individual donors (n = 9). We found that the proportions of total CD8+ T cells and of the putative CD8+ suppressor effector subset (CD28-) were lower in the cell lines derived from cerebrospinal fluid compared with cultures derived from peripheral blood (p less than 0.025 and p less than 0.005, respectively; paired t test), whereas the total CD4+ T-cell proportion was higher (p less than 0.025). For a donor subgroup with "normal" peripheral blood cell-mediated activated suppressor function (63 +/- 2%), mean suppressor cell function mediated by unfractionated or CD8(+)-enriched cells derived from cerebrospinal fluid was significantly lower (38 +/- 7%; p less than 0.01, paired t test). For a donor subgroup with "low" peripheral blood cell-mediated suppression (-1 +/- 10%), suppression mediated by cerebrospinal fluid cells was also "low" (9 +/- 12%). Our results support the postulate that the immune response may be differentially regulated between the central nervous system and peripheral blood compartments.

Adult

Activated suppressor cell function in severely disabled patients with multiple sclerosis.

Defective suppressor cell function has previously been demonstrated in patients with multiple sclerosis (MS) with progressive disease and moderate degrees of disability. In the present study activated suppressor cell function was assessed in patients with documented progressive disease who, at the time of study, had experienced severe disability (Kurtzke score greater than or equal to 6.5) for at least 2 years. We found that mean suppressor levels were significantly increased in this patient group compared with the suppressor levels in the MS patient group with progressive disease but only moderate disability (Kurtzke score of less than or equal to 6.0 within 2 years of study) (59 +/- 8% vs 19 +/- 7%, respectively, p less than 0.01). The mean value in the latter group was significantly reduced compared with the mean value for normal control subjects (47 +/- 4%, p less than 0.01), a finding consistent with previous reports. The results of this study indicate that suppressor cell function, as measured by our assay system, need not be defective in MS patients who have become severely disabled from the progressive form of the disease. Whether the patients who are now severely disabled from progressive MS passed through a phase of disease associated with the same suppressor defects as found in the progressive patients currently with moderate disability will remain speculative until long-term longitudinal studies are performed.

Adult

Multiple sclerosis in childhood: clinical profile in 125 patients.

Multiple sclerosis (MS) has its usual onset in early adult life (average age of 30 years), but age at clinical onset varies considerably. The implications of the age of onset on the clinical presentation and course of MS are unclear. This population-based retrospective study presents data from a group of 125 patients with onset of MS before age 16 years and can thus be considered as representative of MS occurring in childhood. It demonstrates that childhood MS is more frequent in girls, that it very often has a relapsing-remitting course, that initial bouts usually involve afferent structures of the central nervous system, that recovery from these is often complete, and that the pace of the disease is slow.

Adolescent

Analysis of low concentrations of 5-bromo-2-deoxyuridine on sister chromatid exchanges in human lymphocytes.

To determine a concentration of 5-bromo-2-deoxyuridine (BrdU) sufficient for sister chromatid differentiation (SCD), and yet having a minimal effect on the number of sister chromatid exchanges (SCEs), we assessed the effect produced on the number of SCEs by low concentrations (1, 3, and 10 micrograms/mL) of BrdU. SCD was not obtained in 19% of the 31 subjects with 1 microgram/mL of BrdU, while the differentiation was adequate for all samples treated with 3 and 10 micrograms/mL. We statistically analysed the effects of these three different doses and found no significant difference in the number of SCEs obtained with the doses of 1 and 3 micrograms/mL, but a significant difference was observed between these two concentrations and 10 micrograms/mL. We therefore suggest that the dose of 3 micrograms/mL, while sufficient to produce reliable differential staining, still permits an adequate evaluation of the base line of SCEs and appears to enhance the sensitivity of the test to evaluate between-individual variations. Our experiments also underline that SCE counts should include the centromere exchanges.

Adolescent

Clinical and sleep laboratory study of narcoleptic symptoms in multiple sclerosis.

Seventy white patients with a diagnosis of MS and typed for their HLA-A, B, C, and DR were studied. A clinical interview and a questionnaire were used to evaluate the presence of narcoleptic symptoms. The prevalence of sleep attacks, cataplexy, and sleep paralysis was significantly elevated among these patients. However, no difference was seen between DR2 and non-DR2 subjects with regard to the incidence of narcoleptic symptoms. Nine DR2 patients complaining of both sleep attacks and cataplexy were studied in the sleep laboratory for five consecutive naps, but no polygraphic evidence of narcolepsy was found.

Adult

A population-based study of multiple sclerosis in twins.

Results from studies of twin concordance in multiple sclerosis have not conclusively differentiated between environmental and genetic factors that determine susceptibility to the disease. Published studies that have been based on case finding by public appeal have been characterized by difficulties in ascertainment. The data reported here are from a large population-based study of multiple sclerosis in twins, in which ascertainment has been relatively unbiased and the cooperation of patients nearly complete. A total of 5463 patients attending 10 multiple sclerosis clinics across Canada were surveyed. Twenty-seven monozygotic and 43 dizygotic twin pairs were identified, and the diagnosis of multiple sclerosis was verified by examination and laboratory investigation. Seven of 27 monozygotic pairs (25.9 percent) and 1 of 43 dizygotic pairs (2.3 percent) were concordant for multiple sclerosis. The concordance rate for 4582 nontwin siblings of patients at two multiple sclerosis clinics was 1.9 percent, closely paralleling the concordance rate in dizygotic twins. To the extent that the difference in concordance rates between monozygotic and dizygotic twins indicates genetic susceptibility, the results of this study show a major genetic component in susceptibility to multiple sclerosis.

Canada

Analysis of sister-chromatid exchanges (SCEs) in familial and sporadic multiple sclerosis.

The levels of sister-chromatid exchanges (SCEs) were calculated in 17 multiple sclerosis (MS) patients (14 familial and 3 sporadic cases) and 16 healthy controls matched for sex and age. The SCEs were significantly increased for MS patients (p = 0.0002), while there was no statistically significant difference between men and women and between younger and older subjects in both groups. Such factors as familial occurrence and severity of MS, smoking habits, and distribution of lymphocyte subpopulations were discussed. Although there was a significant difference between the MS patients taking medication and the patients taking none (p = 0.038), the latter were still significantly different from the controls (p = 0.035), supporting the fact that the disease itself increases SCEs. Our study, done with 2 doses of BrdU, also shows that the increased SCEs in MS patients are not due to a hypersensitivity to this substance known to be an inducer of SCEs. Thus we suggest that the increased SCEs found are probably disease-related.

Adolescent

Clinical sub-groups of multiple sclerosis in relation to HLA: DR alleles as possible markers of disease progression.

We have examined the distribution of HLA antigens in 70 multiple sclerosis (MS) patients divided in three groups defined according to clinical criteria: benign MS, severe MS, cerebellar MS. We have found a significant association between severe MS and HLA-DR2, and between benign MS of more than 15 years of evolution and HLA-DR3. We review previous work along the same line and conclude that the association of HLA antigens with "clinical subgroups of MS" could indicate a genetically based heterogeneity of the disease and offer help in establishing a prognosis.

Cerebellar Diseases

Isoniazid for tremor in multiple sclerosis: a controlled trial.

We evaluated the effects of isoniazid on tremor in 13 patients with MS. Patients were evaluated before treatment, after 1 month of therapy (1,000 mg daily), and 1 month after the last dose. Ten patients improved on at least one of three methods of evaluation. Transient side effects were common, possibly because there was a high percentage of "slow acetylators"; dosage was reduced by one-half in five patients. Improvement was mild and did not result in significant functional improvement.

Adult