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A D Sadovnick

Publications and source records attributed to A D Sadovnick.

At least 91 records · Page 5Linked to original sources
PubMed1993

The geographic distribution of multiple sclerosis: a review.

The decisive conclusions to be drawn from the geography and prevalence of MS are: (1) a north-south (as well as west-east in the United States) gradient exists independent from genetic/racial factors; (2) major differences in prevalence occur in the absence of difference in latitude; (3) individuals from the same ethnic derivation have either the similar prevalence or have very different prevalence rates in widely separated geographical areas, and (4) specific resistance isolates are shown to exist regardless of latitude. Existing prevalence information leads to the almost inescapable conclusion that the geography of MS cannot be explained by any single known environmental or genetic factor(s) in isolation. A combination of a heterogeneous distribution of both genetic and environmental factors appears to be required to explain the available data on MS and geography.

Causality↗
PubMed1993

Depressive symptoms and family history in seasonal and nonseasonal mood disorders.

OBJECTIVE: The authors' goal was to compare the symptoms and family history of seasonal affective disorder with those of nonseasonal mood disorders. METHOD: From a subspecialty mood disorders clinic, 34 patients with major depression, seasonal pattern (seasonal affective disorder), diagnosed with DSM-III-R criteria, were matched in age, sex, and diagnostic subtype (recurrent unipolar, bipolar I, or bipolar II) to 34 patients with nonseasonal mood disorders. Data on symptoms during the most recent depressive episode were obtained by chart review and compared by using chi-square tests. Family history data for first-degree relatives of patients with seasonal and nonseasonal mood disorders were gathered by using the family history method, and diagnoses were based on Family History Research Diagnostic Criteria. RESULTS: Patients with seasonal affective disorder reported significantly more hypersomnia, hyperphagia, and weight gain and reported less suicidal ideation and morning worsening of mood than the patients with nonseasonal mood disorders. No differences were found in family histories of mood disorders, other psychiatric disorders, and any psychiatric disorder between the groups with seasonal versus nonseasonal mood disorders. Alcoholism was found more frequently in the relatives of the patients with seasonal affective disorder. CONCLUSIONS: Differences in symptoms between seasonal and nonseasonal mood disorders provide some support for seasonal affective disorder as a diagnostic subtype of mood disorders. However, the genetic loading for mood disorders (of unspecified seasonality), as determined by the family history method, is similar for seasonal and nonseasonal mood disorders.

Adult↗
PubMed1993

Obtaining a family psychiatric history: is it worth the effort?

The purpose of this study was to determine whether, for first-degree relatives of patients presenting to a mood disorders clinic, family history information on psychiatric conditions collected by a psychiatrist and incorporated into the patient's medical records is as informative as that gathered during an interview specifically designed to collect family history data. The study group consisted of 472 first-degree relatives of 78 randomly selected index cases from a large mood disorders genetic database. Family history of psychiatric disorders recorded in regular psychiatric medical records ("clinician history"), and data obtained by a genetic counsellor administering specific family psychiatric history questionnaires to patients and multiple family informants ("family history") were compared using a kappa statistic. Good agreement between the two methods on the presence or absence of a psychiatric disorder was found among first-degree relatives of index cases, but poor agreement was found with respect to the presence or absence of a specific mood disorder diagnosis(es) in a relative. The results suggest that a clinician-generated family psychiatric history is sensitive to the presence or absence of a psychiatric disorder when compared to a more structured detailed genetic interview. However, for research purposes, a clinician-generated family psychiatric history of a specific mood disorder diagnosis, without supporting collateral information, may not be reliable for use in supporting a mood disorder diagnosis in a patient and/or his relatives.

Adult↗
PubMed1993

Familial recurrence risks and inheritance of multiple sclerosis.

The cause of multiple sclerosis is unknown. There is considerable circumstantial evidence that multiple sclerosis is a complex trait, probably autoimmune in nature, and is determined by both genetic and environmental factors. It is recognized that relatives of multiple sclerosis patients are at greater risk for developing the disease than the general population, although this risk is still relatively low in absolute terms. Monozygotic co-twins of multiple sclerosis patients appear to have the highest risk of any group of relatives, although the absolute risk is well under 100%, as would be predicted if multiple sclerosis is purely a genetic disorder.

Autoantigens↗
PubMed1992

Life expectancy in patients attending multiple sclerosis clinics.

One multiple sclerosis (MS) is diagnosed, important considerations often include life expectancy and the availability of life insurance. We designed a study specifically to examine life expectancy among MS clinic patients and analyzed the data using standard actuarial methods, both including and excluding suicides. The data show that severe MS disability, as measured by an Expanded Disability Status Score (EDSS) of greater than or equal to 7.5, is a major risk factor for death with case fatality ratios for this group of patients approaching 4 times the rate for controls. Conversely, excluding deaths by suicide, case fatality ratios for those with mild and moderate disability (EDSS less than or equal to 7.0) approach 1.4 times and 1.6 times for age- and sex-matched comparison groups. Life tables indicate that the overall life expectancy for MS is only about 6 to 7 years less than that for the "insured" population without MS.

Adolescent↗
PubMed1992

Epidemiology and genetics of multiple sclerosis.

Epidemiological data suggest an aetiological role for both genetic and environmental factors in multiple sclerosis (MS), but these have yet to be fully characterized. It is probable that MS susceptibility is determined by polygenes but specific loci need to be identified.

Cross-Cultural Comparison↗
PubMed1991

Maternal age and birth defects: a population study.

Since more and more women in developed countries are delaying childbearing to an older age, it is important to find out whether birth defects, other than those resulting from chromosomal anomalies, are related to maternal age. We have studied all 26,859 children with birth defects of unknown aetiology identified among 576,815 consecutive livebirths in British Columbia. All these cases' records were linked with provincial birth records to allow determination of maternal age at birth. We excluded children with chromosomal anomalies and those with other birth defects of known aetiology. Only 3 of the 43 birth defect categories studied showed significant maternal-age-specific trends: there were decreasing linear trends with maternal age for patent ductus arteriosus (chi 2 = 36.65, 1 df, p less than 0.01) and hypertrophic pyloric stenosis (chi 2 = 4.90, 1 df, p less than 0.05) and a bell-shaped curve (risk increasing to maternal age 30 then falling) for congenital dislocatable hip/hip click. The findings from this population-based analysis of no association between the incidence of birth defects of unknown aetiology and advancing maternal age should be reassuring to healthy women who opt to delay childbearing.

Abnormalities, Multiple↗
PubMed1991

The influence of gender on the susceptibility to multiple sclerosis in sibships.

A population-based study of pairs of relatives (siblings, second- and third-degree) concordant for multiple sclerosis did not show an excess of like-sexed pairs. In addition, data on human lymphocyte antigen typing for sibling pairs concordant for multiple sclerosis did not find an increase in haplotype sharing for like-sexed pairs. These data do not support the notion that sex-related factors influence multiple-sclerosis susceptibility in families.

Disease Susceptibility↗
PubMed1991

Parent-child concordance in multiple sclerosis.

It is now recognized that susceptibility to multiple sclerosis (MS) is determined in part by genetic factors. The gene loci influencing MS susceptibility are largely unidentified. In an attempt to better understand the mode of transmission, parent-child concordance for MS was studied in two large, population-based MS clinic populations. Among 75 parent-child pairs concordant for MS, we found 40 mother-daughter pairs, 13 mother-son pairs, 21 father-daughter pairs, and 1 father-son pair. Controlling for the known female preponderance in MS, the data show a paucity of father-son pairs. These data have implications for understanding the mechanisms of inheritance for MS susceptibility as well as for risk counseling in families of patients.

Chi-Square Distribution↗
PubMed1991

Age of onset in siblings concordant for multiple sclerosis.

We have evaluated genetic and environmental influences in multiple sclerosis (MS) by comparing age of onset in 99 sibling pairs concordant for the disease. We used three methods of analysis: (1) comparison of mean differences in age of onset and year of onset, (2) linear regression of differences in age or year of onset vs difference in ages, and (3) intraclass correlation of age of onset which is also used for monozygotic twins concordant for MS. Comparison of the mean differences in age of onset or year of onset is found to be inappropriate and potentially misleading. No significant results were found in linear regression of the age of onset or year of onset vs differences in ages, although a trend towards onset at the same age is present. However, nontwin siblings show a significant intraclass correlation for age of onset (P less than 0.01) as is seen in genetic disorders. A stronger intraclass correlation in age of onset in concordant monozygotic twins vs concordant sibling pairs further suggests that age of onset is partly under genetic control, assuming common exposure to an environmental agent. The results give little support for common exposure to an environmental trigger in concordant MS sibling pairs. They are consistent with a mixture of random independent exposures and common exposures leading to the development of the disease, with the former predominating.

Adolescent↗
PubMed1991

Cause of death in patients attending multiple sclerosis clinics.

Between 1972 and 1988, 145 deaths occurred among 3,126 patients attending the Multiple Sclerosis (MS) Clinics in Vancouver, British Columbia (N = 1,583), and London, Ontario (N = 1,543). We could determine the exact cause of death in 82.1% of cases (119 of 145). Of the 119 patients for whom the cause of death was known, 56 deaths (47.1%) were directly attributed to complications of MS. Of the remaining 63 deaths, 18 (28.6%) were suicides, 19 (30.2%) were due to malignancy, 13 (20.6%) to an acute myocardial infarction, seven (11.1%) to stroke, and the remainder (9.5%) to miscellaneous causes, of which two may have been suicides. The proportion of suicides among MS deaths was 7.5 times that for the age-matched general population, and the proportion of MS deaths from malignancy was 0.67 times that for the age-matched general population. The proportion of deaths due to malignancy and stroke was the same for the MS patients and the age-matched general population.

Acute Disease↗
PubMed1991

APP717, APP693, and PRIP gene mutations are rare in Alzheimer disease.

The amyloid precursor protein (APP) gene codes for the precursor to the beta-protein found in the amyloid deposits of Alzheimer disease (AD). Recently Goate et al. identified in codon 717 of this gene a missense mutation which segregates with AD in a familial AD (FAD) kindred. The same mutation was also found in affected subjects from a second FAD family but not in other FAD families or in normal controls. The following work was undertaken to determine the frequency of the codon 717 mutation in FAD and nonfamilial AD cases and in normal controls. We tested 76 FAD families, 127 "sporadic" AD subjects, 16 Down syndrome cases, and 256 normal controls for this mutation, and none were positive. We also tested for the APP codon 693 mutation associated with hereditary cerebral hemorrhage with amyloidosis-Dutch type, for PRIP gene missense mutations at codons 102, 117, and 200, and for the PRIP insertion mutations which are associated with Creutzfeld-Jakob disease and Gerstmann-Straussler Scheinker syndrome. No examples of these mutations were found in our population. Thus these APP and PRIP mutations are rare in both FAD and nonfamilial AD.

Adult↗
PubMed1990

DNA length polymorphism 5' to the myelin basic protein gene is associated with multiple sclerosis.

A site of DNA polymorphism linked to the myelin basic protein gene, identified as restriction fragment length polymorphism, was analyzed in a population-based study comparing patients with clinically definite multiple sclerosis (MS) and population-matched control subjects. A 0.9-kilobase (kb) genomic DNA fragment (EcoG) encompassing the first exon of the human myelin basic protein gene, located on the long arm of chromosome 18, identified ten alleles arising from a region of DNA, 1.5 kb 5' to the myelin basic protein gene first exon coding region. Produced by RsaI digests and ranging in length from 2.05 to 2.15 kb, these alleles vary in size by up to 100 base pairs due to insertion or deletion, or both, from a 1-kb length of repetitive DNA. Allele frequencies among 65 patients with MS were compared with those of 63 control subjects. Chi square for these data was significant (p less than 0.001), largely due to a preponderance in the patients with MS of alleles in the 2.14- to 2.15-kb range. Comparison of the numbers of patients with MS and control subjects bearing specific alleles showed that 45% of the patients carried at least one allele of 2.14 to 2.15 kb as opposed to 19% of control subjects (p less than 0.005). These data, while preliminary, suggest that patients with MS differ from population-matched control subjects with respect to DNA polymorphism linked to the myelin basic protein gene. Although no pathogenic relationship between this polymorphism and MS can be presupposed, this finding raises the possibility that the myelin basic protein gene or some other myelin basic protein-linked locus may be a factor in susceptibility to MS.

Adult↗
PubMed1990

Heterogeneity in multiple sclerosis: comparison of clinical manifestations in relatives.

Once diagnosed to have MS, relatives of persons who have been previously diagnosed frequently ask whether their disease course will follow that of their relative(s) with MS. The present study compared the following clinical manifestations of MS among 43 index cases and 47 of their relatives, all of whom were diagnosed to have MS and regularly attended the MS Clinic in Vancouver, British Columbia: (i) age of onset of MS, (ii) clinical course, (iii) lesion site(s) and (iv) initial symptom(s) of MS. The results from the present study are preliminary because of the small size of the study group. However, these data suggest that apart from possibly age of onset between sibling pairs, the clinical manifestations of MS are not correlated among relatives who are assessed according to the same methodology. This is significant for counselling newly diagnosed relatives of longstanding MS patients.

Adult↗
PubMed1989

Genetic studies on an Alzheimer clinic population.

All patients attending the Clinic for Alzheimer Disease and Related Disorders have detailed family histories taken by a geneticist. To date, genetic histories are available for 446 consecutive, unrelated individuals. Of these, 151 (33.9%) are diagnosed as having "probable" (N = 141) or "autopsy-confirmed" (N = 10) Alzheimer disease according to recognized criteria. This data base represents a relatively unselected population with respect to more than one person in the family having dementia. Seventy-one of these 151 index cases (47.0%) have a positive family history of dementia, of which 8 (5.3%) may represent the familial (autosomal dominant) form of Alzheimer disease (FAD). Age-corrected empiric recurrence risks for Alzheimer disease/dementia were calculated for first-degree relatives of these 151 index cases using the Kaplan-Meier lifetable method.

Aged↗
PubMed1989

Life tables for Down syndrome.

Life expectancy in Down syndrome was calculated to 68 years, using data for 1610 Down syndrome liveborn individuals among over 1.5 million consecutive British Columbia livebirths. Overall, although survival is significantly poorer than for the general population, over half of Down syndrome individuals can be expected to survive into their fifties, and 13.5% will still be alive at age 68. The data are presented as a life table, a practical format for the clinician and planner.

Actuarial Analysis↗