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Biomedical subjects

R Ottman

Publications and source records attributed to R Ottman.

86 records · Page 5Linked to original sources
PubMed1986

Familial breast cancer in a population-based series.

Breast cancer risks to sisters of breast cancer patients were examined in a population-based series of patients diagnosed in Los Angeles County between 1971 and 1975. Sisters of bilateral patients diagnosed at age 50 years or younger had substantially increased risk (relative risk (RR) = 5.5), and risk was even higher for sisters of bilateral patients diagnosed at age 40 years or younger (RR = 10.5). Half of the breast cancers in sisters of bilateral cases occurred in the family of a single bilateral patient whose disease was diagnosed at age 39 years. Sisters of unilateral patients diagnosed at age 50 years or younger did not have significantly increased risk, but sisters of unilateral patients diagnosed at age 40 years or younger appeared to have increased risk (RR = 2.4). Risk to sisters of bilateral patients was slightly higher if the patient's contralateral diagnoses were less than three years apart than if they were three years apart or greater (RR = 6.3 vs. 3.9), but this difference was not statistically significant.

Adult↗
PubMed1984

Family history as an independent risk factor for coronary artery disease.

The risk of family history of ischemic heart disease independent of other well described risk factors has remained difficult to quantitate. Significant coronary artery disease was determined by coronary arteriography to be present in 223 patients and absent in 57 control subjects. Age, sex, blood pressure, serum cholesterol, cigarette smoking and the presence of diabetes and left ventricular hypertrophy on the electrocardiogram were tabulated for each patient and the data used to assign a risk score based on the American Heart Association multivariate model. Subjects were stratified and matched according to risk score to estimate risk of family history independent of familial aggregation of these seven other risk factors. Angina, myocardial infarction, cardiac death and any ischemic heart disease were ascertained in 1,319 first degree relatives. Odds ratios for overall, stratified and matched comparisons of these end points in relatives of patients and control subjects ranged between 2.0 and 3.9 (p less than 0.01 for all comparisons), indicating a higher frequency of all ischemic heart disease end points in relatives of patients with documented coronary artery disease. Life table comparison of patients at lowest risk with those at higher risk showed significantly greater cumulative frequency and earlier age of onset of all ischemic heart disease end points in relatives of low risk patients. These observations indicate that some of the risk associated with family history is independent of familial aggregation of other known risk factors and suggest that the independent effects of family history may be most important in individuals who otherwise are at low risk.

Adult↗
PubMed1983

Practical guide for estimating risk for familial breast cancer.

Life-table analysis was used to estimate the cumulative risk of breast cancer to various ages for mothers and sisters of breast cancer patients in a population-based series. These cumulative risk estimates were then used to derive a probability of breast cancer diagnosis within each decade between ages 20 and 70 for mothers and sisters, according to age of diagnosis in the patient and whether the disease was unilateral or bilateral. Risks for relatives of premenopausal patients with unilateral disease were no higher than those for relatives of postmenopausal patients. Relatives of premenopausal patients with bilateral disease had higher risk than relatives of patients with unilateral disease, irrespective of age at diagnosis in those with unilateral disease. Sisters were at higher risk than were mothers.

Actuarial Analysis↗
PubMedDate not supplied

Gene-environment interaction: definitions and study designs.

Study of gene-environment interaction is important for improving accuracy and precision in the assessment of both genetic and environmental influences. This overview presents a simple definition of gene-environment interaction and suggests study designs for detecting it. Gene-environment interaction is defined as "a different effect of an environmental exposure on disease risk in persons with different genotypes," or, alternatively, "a different effect of a genotype on disease risk in persons with different environmental exposures." Under this strictly statistical definition, the presence or absence of interaction depends upon the scale of measurement (additive or multiplicative). The decision of which scale is appropriate will be governed by many factors, including the main objective of an investigation (discovery of etiology, public health prediction, etc.) and the hypothesized pathophysiologic model. Five biologically plausible models are described for the relations between genotypes and environmental exposures, in terms of their effects on disease risk. Each of these models leads to a different set of predictions about disease risk in individuals classified by presence or absence of a high-risk genotype and environmental exposure. Classification according to the exposure is relatively easy, using conventional epidemiologic methods. Classification according to the high-risk genotype is more difficult, but several alternative strategies are suggested.

Causality↗
PubMedDate not supplied

Fertility in persons with epilepsy: 1935-1974.

Data from the Rochester-Olmsted County Medical Records Linkage Project were utilized to assess fertility in persons with epilepsy. Population age-specific reproduction rates for Rochester residents for the years 1935-1974 were estimated using the number of live births from the Minnesota Department of Health Statistics and Vital Statistics of the U.S. for comparison with rates in affected persons. Overall, fertility rates were significantly reduced to 80% of expected for affected males and 85% for affected females. Individuals with partial seizures (simple and complex) were disadvantaged, whereas those with generalized onset were not. During the last 20 years of the study period, males were more disadvantaged than females. The male-female difference was greatest during the time of low population fertility (after 1965). Male deficits were more marked after diagnosis; female deficits were more marked before diagnosis. Differences in the proportion of ever-married person-years between the sexes only partially explain the observed differences.

Adolescent↗
PubMedDate not supplied

Genetics of the partial epilepsies: a review.

The research literature is consistent in reporting somewhat less familial aggregation in partial than in generalized epilepsy. However, relatives of patients with partial seizures do appear to have higher seizure risks than relatives of controls, suggesting that genetic factors are important in at least some partial epilepsies. Complex partial epilepsy appears to be only slightly less familial than other types of epilepsy. Relatives of patients with focal EEG abnormalities generally have been found to have lower risk of both EEG abnormalities and epilepsy than relatives of patients with generalized abnormalities. For focal temporocentral abnormalities, however, there is evidence of an important influence of genetic factors.

Disease Susceptibility↗
PubMedDate not supplied

Seizure risk in offspring of parents with generalized versus partial epilepsy.

Genetic factors are commonly assumed to play a more important role in generalized than in partial epilepsy. This study tested this hypothesis by comparing risks of unprovoked seizures in offspring of individuals with generalized versus partial epilepsy. Overall, seizure incidence was no higher in offspring of persons with generalized epilepsy than in offspring of those with partial epilepsy. The number of affected offspring was about three times that expected from population incidence rates, regardless of whether the parent had partial or generalized epilepsy. For the subgroup of generalized cases with absence seizures, however, seizure incidence in offspring was about three times as high as for partial cases. The higher incidence in offspring of absence cases was only partly explained by a higher proportion of absence than partial cases with two factors associated with high risk in relatives, namely early age at onset and idiopathic epilepsy. Offspring of absence cases had higher risk than offspring of other cases not only for absence seizures, but for other seizure types as well, suggesting that absence epilepsy is not genetically distinct from other seizure types of epilepsy. These results suggest that the higher incidence sometimes observed in relatives of patients with generalized epilepsy is due to a small proportion of generalized cases with extremely high familial risks--most generalized epilepsies are no more likely than partial epilepsies to have a genetic basis.

Epilepsies, Partial↗
PubMedDate not supplied

Semistructured interview for seizure classification: agreement with physicians' diagnoses.

A semi-structured interview was developed for classification of seizures in accordance with the 1981 International League Against Epilepsy (ILAE) criteria. The interview was administered over the telephone by trained lay interviewers. Interview-based diagnoses for 50 patients were compared with independent diagnoses by neurologists who also use the ILAE system for seizure classification. Interview diagnoses agreed with those of physicians for broad seizure-type classifications (i.e., partial vs. generalized onset) in 88% of patients and for detailed combinations of seizure type in 64% of patients. Nonchance agreement between the two sources, assessed by the kappa statistic, was excellent for any partial onset (kappa = 0.83), secondarily generalized (kappa = 0.81), and primary generalized tonic-clonic (kappa = 0.76) seizures. Agreement was fair to good for any generalized onset (kappa = 0.70), simple partial (kappa = 0.56), complex partial (kappa = 0.54), and generalized nonconvulsive (kappa = 0.56) seizures. Sensitivity ranged from 0.60 to 1.0 for partial onset seizures, and from 0.43 to 0.67 for generalized onset seizures. Specificity ranged from 0.60 to 0.87 for partial onset seizures, and was 1.0 for generalized onset seizures. Positive predictive value was 0.95 for any partial onset and 1.0 for any generalized onset seizure. These results suggest that this interview can produce accurate diagnoses of major seizure categories. Use of this instrument for clinical epilepsy research should facilitate conduct of large studies at a significant saving of both time and money.

Humans↗
PubMedDate not supplied

Familial aggregation and severity of epilepsy.

Genetic models for complex diseases frequently assume that genetic factors play a greater role in severe forms than in mild forms of disease. This study examined familial aggregation of epilepsy in relation to two measures of severity: duration and remission. The study population comprised 358 offspring born in Rochester, MN, U.S.A., to parents with epilepsy who were diagnosed in Rochester between 1935 and 1979 and followed for greater than or equal to 5 years after the first seizure. Cox proportional hazards analysis was used to examine the effects of duration of the parent's epilepsy (less than 5 vs. greater than or equal to 5 years) and remission of the parent's epilepsy (greater than or equal to 5 years seizure-free) on risk of unprovoked seizures in offspring. The univariate rate ratio (RR) for parent's duration (long vs. short) was 1.1 (95% confidence interval 0.32-3.57). The RR for parent's remission was 2.5 (0.55-11.41), reflecting a higher risk for offspring of remitting parents, which was not statistically significant. Multivariate analysis was used to control for three other parental attributes associated with offspring seizure risk: sex, age at onset of seizures (less than 20 vs. greater than or equal to 20 years), and seizure type (absence vs. other). The RR for duration was not substantially changed in this analysis (1.2; 0.37-4.16). However, the RR for remission dropped to 1.2 (0.25-5.97), suggesting that the higher risk in offspring of remitting parents was largely explained by confounding with other factors that influence offspring seizure risk.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMedDate not supplied

Validity of family history data on seizure disorders.

Accurate family histories of seizure disorders are important for both clinical practice and genetic research. This study evaluated validity of seizure histories of parents and siblings, obtained by interviewing 1,957 adults with epilepsy (probands). Probands were asked two questions to screen for occurrence of seizures in each relative; the first asked about epilepsy specifically, the second asked about "other seizures." For each relative who screened positive for seizures, a detailed clinical description was obtained. The final diagnosis was based on a review of all assembled information. Whenever possible, the proband's mother was interviewed independently about the family history, as were eligible relatives reported to have had seizures. Sensitivity, or the proportion of affected relatives who screened positive for seizures, was higher for epilepsy than for other seizures (87% vs. 32% assuming the mother's report to be correct, and 93% vs. 18% assuming self-report to be correct). For epilepsy, estimates of risk in siblings based on the final diagnoses were similar to previously reported findings in Rochester, Minnesota. For both isolated unprovoked seizures and acute symptomatic seizures, however, risk estimates were lower than in Rochester. These findings suggest that adults with epilepsy can report reasonably accurately about epilepsy in their parents and siblings, but isolated unprovoked seizures and acute symptomatic seizures are underreported.

Epilepsy↗
PubMedDate not supplied

Birth order, sibship size, and risk of epilepsy.

We examined the relation between epilepsy and birth order, using data on 1,950 probands with epilepsy and 4,636 of their full siblings without epilepsy from the Epilepsy Family Study of Columbia University. The proportion of first-born individuals appeared to be higher among probands with epilepsy than among their unaffected siblings, but this relation disappeared after we controlled for the confounding effect of sibship size. With sibship size controlled, the proportion of first-born individuals was similar to that in unaffected siblings for probands with idiopathic/cryptogenic epilepsy, generalized and partial onset seizures, and all ages at onset of epilepsy. Probands with remote symptomatic epilepsy had higher birth orders than their unaffected siblings, even after we controlled for sibship size.

Adolescent↗
PubMedDate not supplied

Likelihood of pregnancy in individuals with idiopathic/cryptogenic epilepsy: social and biologic influences.

We interviewed 1,558 adults with idiopathic/cryptogenic epilepsy ascertained from voluntary organizations and 316 of their siblings without epilepsy to determine their personal history of marriage and pregnancy. We examined the effects of seizure type, age at onset, and family history of epilepsy on the sex-specific likelihood of pregnancy in individuals with idiopathic/cryptogenic epilepsy as compared with their same-sex siblings. Overall, men with idiopathic/cryptogenic epilepsy were only 36% as likely as male unaffected siblings ever to have fathered a pregnancy. In men, the reduced likelihood of fathering a pregnancy was associated with partial-onset seizures, early age at onset (< 20 years), and a negative family history of epilepsy, and the effects of these epilepsy characteristics appeared to be mediated through reduced marriage rates. Among men with epilepsy who had ever been married, reproductive disadvantage was confined to those with early-onset (< 10 years) partial epilepsy. Overall, women with idiopathic/cryptogenic epilepsy were only 37% as likely ever to have had a pregnancy as female unaffected siblings; this effect was not strongly influenced by seizure type, age at onset, or family history of epilepsy. In women who had ever been married, unlike in men, reduced likelihood of pregnancy persisted, regardless of seizure type, age at onset, or family history of epilepsy.

Adult↗
PubMedDate not supplied

Polycyclic aromatic hydrocarbon-DNA adducts in white blood cells and urinary 1-hydroxypyrene in foundry workers.

In an ongoing comprehensive evaluation of biological markers, workers in or near an iron foundry with varying exposure to polycyclic aromatic hydrocarbons (PAH) were analyzed for molecular response to this exposure. Exposure to benzo(a)pyrene, determined by personal monitors worn by the workers (2 to 60 ng/m3), was considerably lower than in a previous study at this foundry (< 50 to 200 ng/m3) (F.P. Perera et al., Cancer Res., 48: 2288-2291, 1988). Two biomarkers, 1-hydroxypyrene in urine measured by high-performance liquid chromatography with fluorescence detection (a measure of internal dose) and PAH-DNA adducts in WBC measured by immunoassay (a measure of biologically effective dose) were assessed to demonstrate their relationship to the lowest exposures yet analyzed in foundry workers. In addition, these markers were analyzed for dose response and interindividual variability. Cigarette smoking, but not age or charbroiled food, influenced the level of 1-hydroxypyrene but not PAH-DNA adducts. When workers were classified into three exposure categories (low, medium, and high), mean 1-hydroxypyrene levels were 2.7, 1.8, and 3.6 mumol/mol creatinine, respectively. Comparisons by analysis of variance showed a significant difference between the groups after controlling for smoking (P = 0.02), but a trend test using multivariate linear regression analysis was not significant (r = 0.27; P = 0.07). Substantial interindividual variation was demonstrated by the 19- to 20-fold range in the values within each of the three exposure groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗