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Biomedical subjects

R Ottman

Publications and source records attributed to R Ottman.

At least 55 records · Page 3Linked to original sources
PubMed1997

The Washington Heights-Inwood Genetic Study of Essential Tremor: methodologic issues in essential-tremor research.

Essential tremor (ET) is the most prevalent movement disorder. It is unknown to what extent ET clusters within families, and the role of genetic susceptibility in etiology of ET has not been adequately investigated at the population level. The problem is largely methodological, with few well-designed studies. The Washington Height-Inwood Genetic Study of ET, begun in 1955, is designed to investigate the genetics of ET using a methodology that has not been applied to ET research to date. Part of the design includes a new set of clinical and electrophysiological diagnostic criteria for ET; the present paper describes this novel study design.

Case-Control Studies↗
PubMed1997

Segregation analysis of cryptogenic epilepsy and an empirical test of the validity of the results.

We used POINTER to perform segregation analysis of cryptogenic epilepsy in 1,557 three-generation families (probands and their parents, siblings, and offspring) ascertained from voluntary organizations. Analysis of the full data set indicated that the data were most consistent with an autosomal dominant (AD) model with 61% penetrance of the susceptibility gene. However, subsequent analyses revealed that the patterns of familial aggregation differed markedly between siblings and offspring of the probands. Risks in siblings were consistent with an autosomal recessive (AR) model and inconsistent with an AD model, whereas risks in offspring were inconsistent with an AR model and more consistent with an AD model. As a further test of the validity of the AD model, we used sequential ascertainment to extend the family history information in the subset of families judged likely to carry the putative susceptibility gene because they contained at least three affected individuals. Prevalence of idiopathic/cryptogenic epilepsy was only 3.7% in newly identified relatives expected to have a 50% probability of carrying the susceptibility gene under an AD model. Approximately 30% (i.e., 50% x 61%) were expected to be affected under the AD model resulting from the segregation analysis. These results suggest that the familial distribution of cryptogenic epilepsy is inconsistent with any conventional genetic model. The differences between siblings and offspring in the patterns of familial risk are intriguing and should be investigated further.

Adolescent↗
PubMed1996

Relations of genetic and environmental factors in the etiology of epilepsy.

We assessed the relations of genetic and environmental factors in the etiology of epilepsy. The study population comprised 9,705 first-degree relatives of 1,951 adults with epilepsy ascertained from voluntary organizations. We calculated standardized morbidity ratios for specific etiologies of epilepsy in the relatives of probands with the same etiologies, using population incidence rates from Rochester, MN, as the reference. Relatives of probands with idiopathic/cryptogenic epilepsy had increased risk for idiopathic/cryptogenic epilepsy and for epilepsy associated with neurological deficit presumed present at birth (cerebral palsy or mental retardation) but not for symptomatic epilepsy associated with postnatal central nervous system insults. Relatives of probands with neurodeficits had increased risks for idiopathic/cryptogenic epilepsy. Risk for epilepsy was not increased among relatives of probands with postnatal symptomatic epilepsy. The degree of increased risk of idiopathic/cryptogenic epilepsy in relatives of probands with idiopathic/cryptogenic epilepsy diminished with increasing age of the relatives; risk was not increased at age 35 or older. These findings support the possibility of shared genetic susceptibility to epilepsy and cerebral palsy, and suggest that the genetic contributions to postnatal symptomatic epilepsy are minimal.

Adolescent↗
PubMed1996

Reproduction among individuals with idiopathic/cryptogenic epilepsy: risk factors for reduced fertility in marriage.

PURPOSE: We wished to determine risk factors for reduced fertility in marriage in men and women with idiopathic/cryptogenic epilepsy and to relate rates of reproduction to the risk of epilepsy in offspring of affected individuals. METHODS: We determined history of pregnancy and child bearing among 863 adults with idiopathic/cryptogenic epilepsy (ascertained from voluntary organizations) who had been married at some time in their lives and from their same-sex siblings without epilepsy who had been married. We examined the effects of seizure type, age at onset, and family history of epilepsy on fertility. Fertility rates were measured as live births per person-year of marriage before and after onset of epilepsy and compared with fertility rates among same-sex siblings without epilepsy by incidence rate ratios (IRR). RESULTS: For both men and women with epilepsy, reduced fertility was observed after, but not before, onset of epilepsy. Among both men and women with epilepsy, those with partial onset and early age at onset (< 10 years) were more reproductively disadvantaged than those with generalized onset and later age at onset. Among those with epilepsy, men with a family history of epilepsy were less reproductively disadvantaged than men without a family history of epilepsy, whereas women with and without a family history of epilepsy did not differ. CONCLUSIONS: We found no evidence of selectively reduced fertility among men with a genetic susceptibility to epilepsy that could account for the higher risk of epilepsy among offspring of affected women than among offspring of affected men.

Adult↗
PubMed1996

Clinical indicators of genetic susceptibility to epilepsy.

We evaluated clinical indicators of genetic susceptibility to epilepsy in the families of 1,957 adults with epilepsy (probands) ascertained from voluntary organizations. Very few of the probands in this series had idiopathic epilepsy syndromes. Among relatives of probands with postnatal CNS insults, risks of epilepsy were no higher than in the general population. Risk was increased in relatives of probands without identified CNS insults (i.e., those with idiopathic/cryptogenic epilepsy) or with neurological deficit presumed present at birth, compared with relatives of probands with postnatal CNS insults. Among relatives of probands with idiopathic/cryptogenic epilepsy, risks were higher in parents and siblings, but not in offspring, of probands with generalized onset as compared with partial onset seizures. Risks in offspring were higher if the probands had onset of idiopathic/cryptogenic epilepsy before age 10 as compared with age > or = 10 years, but risks in parents and siblings were not associated with the probands's age at onset. These results suggest that genetic susceptibility increases risk of some forms of cryptogenic epilepsy and of epilepsy associated with neurological deficit presumed present at birth, but not of postnatal symptomatic epilepsy. The influences on risk in offspring may differ from those in parents and siblings.

Adolescent↗
PubMed1996

How familial is familial tremor? The genetic epidemiology of essential tremor.

Essential tremor (ET) is commonly assumed to be partly genetic. This is due to a seemingly excess aggregation within certain families. There are many families containing more than one member with ET, and some large kindreds with multiple affected individuals. Despite this, the proportion of ET cases with affected family members is not known. Estimates vary from 17 to 100%. Additionally, none of the published studies employed control subjects. Therefore, it is unknown to what extent ET aggregates within families beyond that expected by chance, and the importance of genetic susceptibility in the etiology of ET at the population level has not been established. Additionally, whether or not some clinical subtypes of ET are more likely than others to be influenced by genetic susceptibility is unclear. Some studies suggest that early-onset ET may be familial, although increased awareness and earlier recognition of symptoms is an issue. Although many data support the view that ET susceptibility is inherited in an autosomal dominant manner, most studies are kindreds or service-based studies that might favor selection of families with apparent autosomal dominant modes of inheritance. One community-based study suggested an autosomal dominant mode of inheritance, but this has not been confirmed in studies of more heterogeneous populations. Further understanding of the extent of familial aggregation, extent of genetic heterogeneity, and mode of inheritance is essential for clinical counseling and for further research aimed at localizing and identifying susceptibility genes.

Disease Progression↗
PubMed1996

Is the comorbidity of epilepsy and migraine due to a shared genetic susceptibility?

We tested the hypothesis that the comorbidity of migraine and epilepsy results from a shared genetic susceptibility to the two disorders. We used semistructured telephone interviews to collect information on migraine and epilepsy in the families (parents, siblings, and offspring) of 1,967 adult probands with epilepsy. Epilepsy was defined as a lifetime history of two or more unprovoked seizures, and migraine as self-reported severe headaches with two or more of the following symptoms: unilateral pain, throbbing pain, visual aura, or nausea. As a first test of the hypothesis of shared susceptibility, we assessed risk of migraine in relatives of probands with genetic versus nongenetic forms of epilepsy, using two proxy measures of genetic susceptibility-a first-degree family history of epilepsy and idiopathic/cryptogenic (versus postnatal symptomatic) etiology. Neither of these two measures was associated with risk of migraine in relatives. As a second test, we assessed risk of epilepsy in the relatives of probands with versus without migraine. With the exception of one subgroup (sons of female probands), risk of epilepsy in relatives was not associated with the proband's history of migraine. This pattern of results is inconsistent with the hypothesis of a shared genetic susceptibility to migraine and epilepsy.

Adolescent↗
PubMed1996

Blood lead concentrations and associated factors in residents of Monterrey, Mexico.

Data from interviews of 469 random subjects living in Monterrey, Nuevo León, México were analyzed to investigate factors associated with blood lead (PbB). The following criteria were considered: age, sex, residence zone, occupation, smoking, alcohol consumption, and the use of glazed pottery. Multiple linear regression analysis disclosed that PbB concentration was significantly higher in males, in residents of northeastern (NE) Monterrey, and in blue-collar workers. The highest atmospheric lead (PbA) concentrations of all Monterrey were also found in the NE, the zone that contains the greatest density of factories within the city. PbB and PbA means were significantly correlated (r = 0.964) with regard to the four urban zones considered. It is concluded that increased PbB level in specific categories is probably explained by exposure to PbA originating from industrial emissions.

Adolescent↗
PubMed1995

Birth cohort and familial risk of epilepsy: the effect of diminished recall in studies of lifetime prevalence.

This study separated the effects of age, birth cohort, and generation (parents, siblings, and offspring) on familial risk of epilepsy. The study population comprised 9,741 parents, siblings, and offspring of 1,957 adult probands with epilepsy ascertained from 10 voluntary organizations in New York, New Jersey, Connecticut, and Massachusetts between 1985 and 1988. Semistructured telephone interviews with probands and selected family members were used to collect data on the history of epilepsy in the relatives. The risk of epilepsy increased in successive generations (cumulative incidence to age 40: parents, 1.8%; siblings, 2.9%; offspring, 5.6%) but, with the exception of one subgroup (offspring of female probands), these differences disappeared after controlling for age and birth year of the relatives. With age and relationship controlled, the risk of epilepsy increased approximately 50% for each 20 advancing years of birth. Population-based data indicate that age-specific incidence rates of epilepsy have not increased during the age and time periods investigated here; thus, the most plausible explanation for the findings is that epilepsy is underreported in persons born in earlier time periods. These results illustrate a general phenomenon of underreporting in studies of lifetime prevalence, and they caution against interpreting apparent cohort effects in such studies as evidence of secular changes in incidence.

Adolescent↗
PubMed1995

Apolipoprotein E and Alzheimer's disease: ethnic variation in genotypic risks.

The presence of the apolipoprotein epsilon 4 (apo epsilon 4) allele significantly increases the risk of Alzheimer's disease. Whether this is due to biological effects of the apo epsilon 4 protein or reflects linkage disequilibrium with an as yet unidentified Alzheimer's disease susceptibility gene is of critical importance. In a community study in northern Manhattan we found a fivefold increase in the risk of Alzheimer's disease among African-Americans, Hispanics, and whites homozygous for apo epsilon 4. Overall, the risk between Alzheimer's disease and apo epsilon 4 heterozygosity was also increased by twofold, but the association was somewhat weaker for African-Americans than for Hispanics and whites. In contrast, the apo epsilon 2/epsilon 3 genotype was associated with an eightfold increased risk of Alzheimer's disease in African-Americans but it was associated with reduced risk in whites. Variability in the strength and type of association between Alzheimer's disease and the apo E polymorphisms in the three ethnic groups could not be fully explained by age differences. The allelic frequency of apo epsilon *4 was significantly higher in patients than control subjects in all ethnic groups at age 70 or younger, reflecting the higher proportion of apo epsilon 4 homozygotes, but this difference diminished with increasing age. The allelic frequency of apo epsilon *2 for African-Americans and Hispanics, but not whites, was significantly higher in patients than control subjects, but only after age 70.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1995

Localization of a gene for partial epilepsy to chromosome 10q.

There is strong evidence for a genetic contribution to epilepsy, but it is commonly assumed that this genetic contribution is limited to 'generalized' epilepsies, and that most forms of 'partial' epilepsy are nongenetic. In a linkage analysis of a single family containing 11 affected individuals, we obtained strong evidence for localization of a gene for partial epilepsy. This susceptibility gene maps to chromosome 10q, with a maximum two-point lod score for D10S192 of 3.99 at theta = 0.0. All affected individuals share a single haplotype for seven tightly linked contiguous markers; the maximum lod score for this haplotype is 4.83 at theta = 0.0. Key recombinants place the susceptibility locus within a 10 centimorgan interval.

Adolescent↗
PubMed1995

Synergistic effects of traumatic head injury and apolipoprotein-epsilon 4 in patients with Alzheimer's disease.

The apolipoprotein-epsilon 4 allele increases the risk of Alzheimer's disease (AD), but cerebral deposition of beta-amyloid with age, a genetic mutation, or head injury may contribute to the pathogenesis of this disease. We examined the risks of AD associated with traumatic head injury and apolipoprotein-epsilon 4 in 236 community-dwelling elderly persons. A 10-fold increase in the risk of AD was associated with both apolipoprotein-epsilon 4 and a history of traumatic head injury, compared with a two-fold increase in risk with apolipoprotein-epsilon 4 alone. Head injury in the absence of an apolipoprotein-epsilon 4 allele did not increase risk. These data imply that the biological effects of head injury may increase the risk of AD, but only through a synergistic relationship with apolipoprotein-epsilon 4.

Aged↗
PubMed1995

CYP1A1 messenger RNA levels in placental tissue as a biomarker of environmental exposure.

The human CYP1A1 gene codes for an inducible enzyme system involved in biotransformation of certain xenobiotics, including polycyclic aromatic hydrocarbons; some of the metabolites are carcinogenic and mutagenic. Effects of environmental exposures (smoking, air pollution, and diet) on CYP1A1 gene induction in placental tissue and the modulation of induction by the CYP1A1 MspI RFLP were evaluated in two groups from Poland: 70 mother-child pairs from Krakow, a city with elevated air pollution; and 90 pairs from Limanowa, a less polluted area. Compared to placentas from nonsmoking women, CYP1A1 mRNA levels were significantly increased in placentas from current smokers (P < 0.001). Ex-smokers also had significantly higher placental mRNA levels, including women who quit smoking prior to pregnancy (P < 0.01). A marginal increase in CYP1A1 mRNA with environmental tobacco smoke exposure was evident. Within Krakow, there was an increase in CYP1A1 mRNA with ambient pollution at the place of residence for each woman, which was significant among women who were not employed away from the home (P < 0.05 controlling for smoking status, diet, and use of coal for heating). Significant increases in mRNA were associated with dietary consumption of smoked meat, cheese, and fish (P < 0.01). The CYP1A1 MspI RFLP was not a significant determinant of CYP1A1 mRNA levels after controlling for smoking and other variables. Human placenta provides a readily available and responsive system that can serve as a model for evaluating environmental and genetic determinants of CYP1A1 induction.

Adult↗
PubMed1995

Decline of DNA damage and other biomarkers in peripheral blood following smoking cessation.

Serial samples from 40 heavy smokers ( > or = pack/day for > or = 1 year) enrolled in a smoking cessation program were assayed for cotinine, polycyclic aromatic hydrocarbon (PAH)-DNA, 4-aminobiphenyl-hemoglobin (4-ABP-Hb) adducts, and glycophorin A (GPA) mutations. Blood samples were taken while subjects were smoking, and 10 weeks and 8 and 14 months after quitting. Cotinine was used to assess compliance with the cessation protocol. A significant reduction in mean PAH-DNA and 4-ABP-Hb adducts was observed after cessation in all persons who were cotinine-verified quitters ( < or = 25 ng/ml) for > or = 8 months (P < 0.05). Neither the GPA N/phi nor the GPA N/N mutation Vf was significantly reduced after smoking cessation, but results are limited by the small number (n = 18) of heterozygous individuals studied. The substantial reduction (50-75%) in PAH-DNA and 4-ABP-Hb adduct levels after quitting indicates these carcinogen adducts are reflective of smoking. Passive exposure to smoke at home was significantly associated with PAH-DNA adducts in active smokers and in ex-smokers 10 weeks after quitting (P < 0.01). The estimated half-life of the PAH-DNA adducts in leukocytes is 9-13 weeks by inspection of the mean biomarker levels from baseline and 10 weeks sample and 23 (95% confidence interval, 10-36 weeks) using a linear regression model that adjusted for background.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Biomarkers of environmental tobacco smoke in preschool children and their mothers.

BACKGROUND: Adverse health effects attributable to environmental tobacco smoke (ETS) include respiratory illness and lung cancer in nonsmokers. There is accumulating evidence that children may be at heightened risk of cancer later in life as a result of exposure to carcinogens during their early development. It is of concern that as many as 9 million American children under the age of 5 years may be exposed to ETS. PURPOSE: Our goal was to assess whether levels of cotinine and polycyclic aromatic hydrocarbon-albumin (PAH-albumin) are associated with ETS exposure in children and in women of reproductive age, after accounting for background exposures to PAHs in the diet, workplace, and the home environment. METHODS: The study cohort was composed of 87 Hispanic and African-American mothers and 87 of their preschool children (2-5 years of age). Plasma cotinine was analyzed by gas chromatography; PAH-albumin adducts in peripheral blood were analyzed by enzyme-linked immunosorbent assay. Exposure data were obtained by interview-administered questionnaires. RESULTS: Both cotinine and PAH-albumin were significantly higher in the children whose mothers smoked than in the children of nonsmoking mothers (P < .001 and P < .05, respectively). Among the children of nonsmoking mothers, cotinine levels were also significantly higher in those who had ETS exposure from others in the household compared with the unexposed children. By regression analysis, after adjustment for ethnicity, there was a significant dose-response relationship between cotinine and the number of cigarettes smoked per day by the mother, both in the children (partial r2 = .23; P = .01) and in the mothers (partial r2 = .22; P = .01). Among the nonsmoking mothers, regression of biomarkers against total passive smoking exposure also showed a significant association with cotinine (r2 = .25; P = .04). PAH-albumin did not show the same dose-related response with the smoking variables. Mothers' cotinine levels were significantly correlated with those of their children (r = .76; P < .001) as were PAH-albumin adducts (r = .27; P = .014). CONCLUSION: ETS exposure of young children via their mothers' smoking is associated with increases not only in the internal dose of ETS (cotinine), which has been previously reported, but also in the biologically effective dose of the carcinogenic (PAH) components of ETS (PAH-albumin adducts). This observation underscores the carcinogenic and public health hazard of ETS. IMPLICATIONS: Given the relatively low level of ETS exposure in this study, these results reinforce the need for effective programs aimed at smoking prevention and cessation among women, particularly women of reproductive age and minorities.

Adult↗
PubMed1994

Increased risk of Alzheimer's disease in mothers of adults with Down's syndrome.

Most adults with Down's syndrome (DS) develop neuropathology characteristic of Alzheimer's disease (AD) by the age of 40. Most of the non-dysjunction events in DS are of maternal origin. We postulated therefore that a shared genetic susceptibility to DS and AD would be associated with an increased frequency of AD among mothers, but not fathers, of individuals with DS. We further hypothesised that the shared susceptibility could involve an accelerated ageing process, leading to the birth of a child with DS to a relatively young mother and to an increased risk of dementia in the mother and her relatives. Families of 96 adults with DS and of 80 adults with other forms of mental retardation were ascertained through the New York State Developmental Disabilities services network. A semi-structured interview was used to obtain information on the presence or absence of non-stroke-related dementia and other disorders in parents. There was an increase in risk of dementia among mothers of DS probands compared with control mothers (risk ratio 2.6 [95% CI 0.9-7.3]). The risk of dementia among mothers who were 35 or younger when their DS children were born was 5 times that of control mothers (4.9 [1.6-15.4]). There was no increase in risk of dementia among mothers who were older (> 35 years) at the proband's birth (0.8 [0.2-3.4]). There was no difference in risk of dementia between fathers of DS cases and fathers of controls (1.2 [0.4-3.9]) and no discernible influence of age on this risk. Familial aggregation of dementia among mothers of adults with DS supports the hypothesis of a shared genetic susceptibility to DS and AD.

Adult↗
PubMed1994

Epidemiologic analysis of gene-environment interaction in twins.

Our aim was to develop a simple method for testing gene-environment interaction in twin data ascertained through affected twins (probands), with known exposure status of both cotwins. To this end we derived formulae for two epidemiologic measures, as a function of prevalence of an exposure and genotype, and disease risk conditional on exposure and genotype: (1) relative risk of disease in exposed vs. unexposed cotwins, stratified by zygosity and proband exposure status (RRE), and (2) relative risk of disease in MZ vs. DZ cotwins, stratified by exposure status of proband and cotwin (RRZ). Then we investigated the behavior of these two measures under different assumptions about the relations between exposure and genotype in terms of their effect on disease risk. If an exposure has a different effect in the presence vs. absence of the genotype, RRE differs between MZ and DZ cotwins. Similarly, if a genotype has a different effect in exposed vs. unexposed persons, RRZ differs between exposed and unexposed cotwins. However, large differences in RRE between MZ and DZ cotwins, or large differences in RRZ between exposed and unexposed cotwins, do not occur except under very extreme conditions, such as a genotype that increases disease risk in exposed individuals, and has a protective effect in unexposed individuals. These results suggest that power to detect gene-environment interaction is limited with this approach. Conversely, if large differences in RRE or RRZ are observed, they are likely to reflect strong gene-environment interaction.

Bias↗