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R Detels

Publications and source records attributed to R Detels.

At least 199 records · Page 11Linked to original sources

Segregation and linkage analysis of 40 multiplex multiple sclerosis families.

40 multiplex multiple sclerosis (MS) families were analyzed for evidence of an MS susceptibility gene linked to the HLA region of the sixth chromosome. We assumed that population associations between specific HLA alleles and MS are due to linkage disequilibrium, so preference was given to hypotheses compatible with tight linkage, and explanations were sought for conflicting evidence. The analyses proceeded in two steps: (1) segregation analysis using the computer program POINTER, and (2) linkage analysis using LINKAS, first assuming linkage equilibrium and then allowing for linkage disequilibrium and etiological heterogeneity. The results of the segregation analyses were indeterminate. The results of the linkage analyses suggest that analyses that do not allow for disequilibrium lose substantial evidence on linkage. Of the models that were investigated under linkage disequilibrium, the best fit is with a model of complete linkage (theta= 0.0) in 75% of the pedigrees and no linkage in the remaining pedigrees. We were unable, however, to statistically reject another model involving loose linkage and no heterogeneity.

Chromosomes, Human, 6-12 and X↗

The UCLA population studies of chronic obstructive respiratory disease. IV. Respiratory effect of long-term exposure to photochemical oxidants, nitrogen dioxide, and sulfates on current and never smokers.

Questionnaires, spirometry, and the single-breath nitrogen test were administered to 3,192 participants 25 to 39 yr of age in area exposed to low concentrations of all pollutants (Lancaster, California) and to 2,369 similar participants living in an area exposed to high concentrations of photochemical oxidants, nitrogen dioxide, and sulfates (Glendora, California). The prevalence of symptoms and results in the majority of the tests were worse in the polluted area between current and never smokers and men and women. Those tests associated primarily with small airways (Vmax50, Vmax75, delta N 2(750-1250) showed little or no difference between areas. The difference in the prevalence of participants with a poor FEV1 and/or poor FEV1 and/or poor FVC and in the mean Vmax and closing volume was greater between areas than between smoking categories. These results suggest that long-term exposure to high concentrations of photochemical oxidants, NO2, and sulfates at place of residence may result in measurable impairment in both current smokers and never smokers. Firmer documentation of this effect will require following these populations for changes in lung function that correlate with pollutant exposures.

Adult↗

Changes in immune response during responses in MS patients.

Changes in clinical status and in two measures of immune function were followed for 21 months (median) in 106 multiple sclerosis (MS) patients and cohabitant controls. Antibody titers to measles, cytomegalovirus, and herpesvirus 1 and 2, and leukocyte migration inhibition indexes (LMIs) to measles and streptokinase/streptodornase (SKSD) were measured at 3- to 6-month intervals and at time of exacerbation in the index case. There were 36 exacerbations in 25 patients. Mean baseline antibody titers and LMI to measles were higher in cases than in controls. No consistent changes occurred in antibody titers to any of the viruses, non in LMI to SKSD. LMIs to measles were lower in most MS patients during exacerbations than before or after exacerbations. This apparent improvement in cell-mediated immune response to measles only during exacerbations may reflect aberrant immune regulation in MS patients, response to recrudescence of a latent agent, or some other phenomenon as yet undefined.

Antibody Formation↗

Measles antibody titers in multiple sclerosis patients and HLA-matched and unmatched siblings.

Antibody titers to measles, cytomegalovirus, and herpesviruses 1 and 2 were compared for siblings of multiple sclerosis (MS) patients sharing two, one, and no histocompatibility antigen haplotypes with the case. Significant differences were observed only for measles. Titers were significantly lower in siblings sharing no haplotypes with the case. Within case-sibling pairs, the presence of HLA-A-A3 and/or B7 affected measles antibody titers more than the presence of MS. These findings suggest that the immune response to measles in these sibships is influenced by the presence of HLA-A-A3 and/or B7 as well as another familial factor.

Adult↗

Residential mobility and long-term treatment of hypertension.

Maintenance of long-term care of populations with high mobility patterns poses problems for programs designed to prevent and treat cardiovascular and other chronic diseases. The Hypertension Detection and Follow-up Program (HDFP)--a community-based screening and treatment program implemented in 1973--provided an opportunity to examine residential mobility among adults under long-term treatment in 13 communities. Whereas 11% of hypertensives included in the HDFP changed residence in the first two years of the study, only 4% moved outside the service areas of the programs. Although a higher proportion of blacks (to whites) moved within the service areas, a similar proportion moved outside the service areas. This low residential mobility, especially the low rate of movement outside the service areas of the treatment centers, suggests that mobility of cohorts under long-term treatment and observation may present lesser problems to continuous, long-term community health care programs than do other factors affecting adherence.

Community Health Services↗

Genetic susceptibility to multiple sclerosis: a linkage analysis with age-of-onset corrections.

To test the hypothesis that a multiple sclerosis susceptibility (MSS) gene is linked to the HLA loci, formal linkage analysis was conducted on 40 multiplex families, 20 each from the Seattle and Los Angeles areas. The computer program LIPED was utilized. A dominant model of inheritance was assumed. Penetrance values of 0.05, 0.35, and 0.67 were entered into the analyses, and an age-of-onset correction was incorporated. The resulting lod scores were supportive of linkage at the lower penetrance levels. The maximum lod score, 2.411, at an estimated recombination fraction of 0.10 in both males and females, was generated at a penetrance value of 0.05. With a penetrance value of 0.67, the lod scores did not support linkage. Under an autosomal dominant model of inheritance, the results were supportive of linkage when the presumed penetrance of the MSS gene is low. The results also confirmed the importance of incorporating an age-of-onset correction into linkage analyses.

Age Factors↗

The need for epidemiologists.

The increasing need for epidemiologists in biomedical research has been studied by polling organizations with present and potential needs for epidemiologic services. The research institutes of the National Institutes of the National Institutes of Health and the schools of medicine reported the greatest estimated need among the respondents. They and others polled indicated a substantial need for master's and doctoral level epidemiologists that cannot be fulfilled by current training programs in epidemiology. Broad, sound methodological training applicable to all health problems, and increased funding for support of epidemiologic trainees and training programs in institutions, which would make epidemiology training competitive with that in other fields, are strongly recommened.

Epidemiology↗

The UCLA population studies of chronic obstructive respiratory disease. I. Methodology and comparison of lung function in areas of high and low pollution.

The prevalence of symptoms of chronic obstructive respiratory disease and of functional respiratory impairment was determined in 3465 residents (70 per cent of enumerated) of an area historically exposed to photochemical/oxidant pollutants and 4509 residents (79 per cent of enumerated) of an area exposed to low levels of chemical pollutants. Tests administered included the NHLI questionnaire, electronic volume spirometry, whole body plethysmography, and the single-breath nitrogen test (deltaN2750-1250 and closing volume). Cough and cough with sputum were more frequently reported in the low-pollution area. Lung function was better among residents of the low-pollution area according to FEV1, FVC, maximal expiratory flow rates, closing volume fraction, thoracic gas volume, and airway resistance. Maximal mid-expiratory flow rate, considered to be a sensitive spirometric test for detection of small airways disease, was similar in residents of both areas. Mean deltaN2750-1250 was slightly worse among residents of the low-pollution area. Findings suggest that adverse effects of long-term exposure to photochemical/oxidant pollutants may occur primarily in the larger airways both among smokers and never smokers. The greatest differences between areas were observed in residents 18-59 years of age, suggesting that long-term exposure may be required to cause measurable impairment and that these differnces may be obliterated by such factors as smoking, differential out-migration and differential survival.

Adolescent↗

Genetic susceptibility to multiple sclerosis.

Previous studies of histocompatibility (HLA) types in multiple sclerosis (MS) families did not provide convincing proof of an HLA-linked susceptibility factor. In 12 families we studied, all MS cases in each family shared at least one chromosome. The probability of this occurring in the absence of genetic linkage is approximately 0.001. The estimated penetrance is 5 percent, implying that the genetic susceptibility factor may be a necessary but not a sufficient cause of MS. Additional studies are needed to identify other differences between affected and unaffected susceptible individuals.

Female↗

HLA types and immunity in multiple sclerosis.

HLA types and levels of humoral and cell-mediated immune responses to several antigens were studied in a large group of patients with multiple sclerosis, and in controls. Patients were more likely than controls to have the DRw2 antigen. They had higher mean antibody titers to measles but not to cytomegalovirus, herpes 1, or herpes 2, and had less competent cell-mediated responses. Antibody titers to measles were lower and cell-mediated immune responses were more effective in patients with the DRw2 antigen in patients than in patients without it. This apparent specificity for measles suggests that the etiology of multiple sclerosis is related to the immune response to measles or related viruses.

Antibodies, Viral↗

Multiple sclerosis and housedogs: a case-control study.

A case-control study was conducted to examine the possible association between ownership of housedogs early in life and later development of multiple sclerosis (MS). Sixty MS patients were compared with 60 neighborhood controls matched for age, sex, and race. There was no significant difference between cases and matched controls in housedog ownership, duration of ownership, or age at first exposure to housedogs over the interval from birth to 19 years of age.

Adolescent↗