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Biomedical subjects

L M Jack

Publications and source records attributed to L M Jack.

14 recordsLinked to original sources
PubMed2005

Dopamine receptor DRD2 genotype and smoking cessation outcome following treatment with bupropion SR.

The A1 allele of the dopamine D2 receptor gene (DRD2) is associated with a reduced number of dopamine binding sites in the brain and with the increased likelihood of substance abuse and addictive behavior. In a study of smokers enrolled in an open-label, randomized effectiveness trial, we investigated whether variants in the DRD2 receptor gene are associated with smoking cessation outcomes following treatment with a combination of bupropion SR and behavioral counseling. Adherence to treatment and point-prevalent smoking status were assessed at 3 and 12 months, respectively, following a target quit date. Compared to women who carry both A2 alleles, women with at least one A1 allele were more likely to report having stopped taking bupropion due to medication side effects (odds ratio (OR)=1.91, 95% confidence interval (CI)=1.01-3.60; P<0.04) and at 12 months were somewhat more likely to report smoking (OR=0.76, 95% CI=0.56-1.03; P<0.076). Significant associations or trends were not observed in men. In women, individual variability in responsiveness to bupropion-based treatment may be partially due to differences in genetic variants influencing dopamine receptor function.

Adult↗
PubMed2000

The contribution of genetic influences to measures of lower-extremity function in older male twins.

Tests of balance, gait, and endurance were administered to 95 monozygotic (MZ) and 92 dizygotic (DZ), white male twins aged 68 to 79 years who had been born in the United States. Within-twin-pair correlations were calculated for each individual task and for an overall summary performance score. These were subjected to structural equation modeling to determine the contributions of genetic and environmental influences to individual differences in performance scores. MZ intraclass correlations were significant and greater than DZ correlations for the 8-foot walk and the repeated chair stands task, but not for the standing balance task. The heritability of the lower-extremity summary score was 57%, of which 39% was due to additive genetic effects and 18% due to nonadditive effects. In addition, we found that genetic influences contributed primarily to twin similarity in the poorest quartile of performance, whereas shared environmental influences contributed to twin similarity in the best quartile.

Aged↗
PubMed1999

Differential genetic influence for components of memory in aging adult twins.

OBJECTIVE: To investigate the relative proportion of genetic and environmental contributions to verbal memory in community-dwelling World War II veteran twins. DESIGN: The California Verbal Learning Test (CVLT) was administered to 94 monozygotic (MZ) and 89 dizygotic (DZ) elderly male twin pair participants in the fourth examination of the National Heart, Lung, and Blood Institute Twin Study. SETTING: Subjects voluntarily participated on an outpatient basis at a research or medical center facility in 1 of 4 sites in the United States. PARTICIPANTS: Subjects had a mean age of 71.8 years (SD, 2.9 years), a mean educational level of 13.6 years (SD, 2.8 years), and no history of stroke and/or a Mini-Mental State Examination score of 23 or greater. MAIN OUTCOME MEASURES: Twin pair similarity in performance on 4 factor analytically derived components of the CVLT measuring verbal learning and memory, response discrimination, learning strategy, and recognition memory. RESULTS: The MZ intraclass correlation was significantly larger than the DZ correlation for verbal learning and memory (I<.001) but not for the other 3 components of memory. Using maximum likelihood methods, the best-fitting genetic model indicated that verbal learning and memory has a substantial genetic component (56% of total variance), whereas response discrimination has a much smaller, although still detectable, genetic component (24% of total variance). There is no evidence of genetic influence on learning strategy or recognition memory. CONCLUSION: Differential contribution of genetic and environmental influences to specific components of memory suggest that, in this group of elderly male twin pairs, some components may be more amenable to intervention than others.

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PubMed1998

Evidence for genetic variance in white matter hyperintensity volume in normal elderly male twins.

BACKGROUND AND PURPOSE: White matter hyperintensities (WMHs), as detected by MRI, are common among the elderly and are frequently interpreted as representing a subclinical form of ischemic brain damage. We used volumetric MR techniques to investigate the contribution of genes and the environment to measures of brain morphology in a sample of community dwelling elderly male twins. METHODS: Brain MR (1.5 T) scans were obtained from 74 monozygotic (MZ) and 71 dizygotic (DZ), white, male, World War II veteran twins born in the United States and age 68 to 79 when scanned. MR quantification used a previously published semiautomated segmentation algorithm to segment brain images into total brain, cerebrospinal fluid (CSF), and WMH volumes. Twin pair covariances were computed for each measure, and structural equation genetic models were fitted to these data. RESULTS: Total cranial, brain parenchyma, CSF, and WMH volumes were highly correlated in MZ pairs, and correlations in MZ pairs were significantly greater than those in DZ pairs. Structural equation modeling indicated heritabilities of 91%, 92%, and 73%, respectively, for total cranial, brain parenchyma, and WMH volumes. Correction for age and head size reduced the heritability of brain parenchyma to 62% (95% confidence interval, 56% to 68%) and the heritability of WMH volume to 71% (95% confidence interval, 66% to 76%). Proband concordance rates for large amounts of WMH were 61% in MZ pairs and 38% in DZ pairs, compared with a prevalence of 15% in the entire sample. CONCLUSIONS: This study is the first to quantify the relative contribution of genetic and individual environmental influences to measures of brain morphology in the elderly.

Aged↗
PubMed1998

Association of midlife blood pressure to late-life cognitive decline and brain morphology.

OBJECTIVE: To investigate the association between midlife systolic blood pressure (SBP) and late-life cognitive decline and brain morphology in a sample of community-dwelling elderly men 68 to 79 years of age. METHODS: Subjects are surviving members from the prospective National Heart, Lung, and Blood Institute Twin Study (intake, 1969 to 1972) who, when examined for a fourth time in 1995 through 1997, underwent brain MRI and repeated assessment of neurobehavioral functioning. Quantification of the MR images determined cerebral volume and total volume of white matter hyperintensities (WMHIs) for 392 subjects. Midlife SBP levels measured in 1970, 1980, and 1985 were used to classify subjects into low, medium, and high midlife SBP categories. A 10-year change in performance on the Mini-Mental State Examination, Digit Symbol Substitution Test, Benton Visual Retention Test, and Verbal Fluency Test was also calculated for these subjects. For all reported analyses, patients were treated as genetically unrelated individuals. RESULTS: Subjects with high midlife SBP experienced a greater decline in cognitive performance and had larger WMHI volumes at follow-up in late life than did those with low midlife SBP. Decreased brain parenchyma and increased WMHI volumes were associated with decline in neurobehavioral functioning as measured in late life independent of age, education, and baseline levels of cognition. CONCLUSIONS: Midlife SBP is a significant predictor of both decline in cognitive function and MR volumetric measures of brain atrophy in late life. Because decline in neurobehavioral functioning was associated with decreased brain volume and increased WMHI volume, we conclude that the long-term impact of elevated SBP on decline in late-life neurobehavioral functioning is likely to be mediated through its chronic, negative effect on structural characteristics of the brain.

Adult↗
PubMed1997

Subgroups of smokers with different success rates after use of transdermal nicotine.

To identify subgroups of smokers with different success rates, we applied "tree-structured survival analysis" (TSSA) to data from a previously published trial of transdermal nicotine. The subjects who received active treatment (14 mg patch, n = 275, or the 21 mg patch, n = 262) constituted the sample for this analysis. Using age, gender, the Fagerstrom Tolerance Questionnaire (FTQ), motivation to quit, number of cigarettes smoked at baseline, and body mass index (BMI) as classification variables, TSSA identified two subgroups within the 14 mg patch group and four subgroups of smokers within the 21 mg patch group. Among those receiving the 14 mg patch, individuals with a BMI greater than 26.4 kg/m2 relapsed sooner than did those with a BMI less than or equal to this value. Within the 21 mg patch group, the survival curve for males was significantly different from that observed in females, with males experiencing a longer time to relapse after treatment than did females. Among females, those with a higher motivation to quit relapsed more slowly than did those women with less motivation to quit. This information may be helpful to clinicians seeking to match specific patients to specific treatments with traditional nicotine in order to maximize treatment outcomes.

Administration, Cutaneous↗
PubMed1995

Ambulatory monitoring of heart rate and blood pressure during the first week after smoking cessation.

To investigate the timecourse of cardiovascular changes immediately after smoking cessation, 16 subjects wore ambulatory monitors on alternate days during a 1-week residential smoking cessation program. Heart rate was significantly elevated at the time of cessation, then declined steadily until 6 h after cessation, when it reached the level of subsequent nonsmoking days. Systolic and diastolic blood pressures were elevated to a lesser degree for the same period after cessation. The timing of the decline in heart rate and blood pressure was coincident with the timing of an increase in withdrawal symptoms and has implications for laboratory and epidemiologic studies.

Adult↗
PubMed1994

Effect of smoking cessation and relapse on cardiovascular levels and reactivity.

This study was designed to investigate the effect of smoking cessation on heart rate, blood pressure, and finger temperature absolute levels and reactivity to a range of laboratory challenges. The 148 quitters (mean age = 43.3 years, mean amount smoked = 24.9 cigarettes per day, mean years smoked = 25.2) completed three assessments: an average of 4 +/- 2.8 days before cessation (Exam 1), an average of 2 +/- 1.0 days after cessation (Exam 2), and an average of 20 +/- 5.5 days after cessation (Exam 3). A nonsmoking group (n = 39) was similarly assessed three times to control for effects related to repeated testing. Comparison of group changes from Exam 1 to Exam 2 indicated that smoking cessation produced a significant decrease in heart rate during rest and during all stressors (mean = -8.9 bpm). Those quitters who remained abstinent or smoked occasionally showed minimal changes in heart rate from Exam 2 to Exam 3, but those quitters who returned to their previous smoking level showed a significant increase in heart rate from Exam 2 to Exam 3. None of the indices of cardiovascular reactivity changed across exams, and neither did absolute levels of blood pressure or finger temperature at rest or during stressors. The possible mechanisms producing a selective heart rate decline after smoking cessation in the absence of pressor or vasodilation effects are discussed.

Adult↗
PubMed1993

Differential rates of relapse in subgroups of male and female smokers.

Subjects for this study were 265 participants of stop-smoking clinics (mean age = 42.6 years; average number of cigarettes smoked daily = 26.0) who were examined before and immediately after cessation and then followed for 1 year. The objective of this study was to identify subgroups of smokers with different rates of relapse using tree-structured survival analysis, a multivariate approach to classification. Five distinct subgroups that differed with respect to the rate of relapse were identified: (I) subjects (n = 15) with very low precessation cotinine levels (< or = 129 ng/ml), who had an exceptionally low rate of relapse (mean abstinence time = 270 days); (II) women 32 years old and younger (n = 24), who had a very high rate of relapse (mean abstinence time = 30.5 days); (III) women over 32 years old (n = 121), with the next highest rate of relapse (mean abstinence time = 98.9 days); (IV) men 36 years old and younger (n = 31), who had a mean abstinence time of 196.7 days; and (V) men over 36 years old (n = 74), who abstained an average of 130.2 days before relapsing. Relapse curves for all groups (except III vs V) differed significantly from each other, p < 0.05. Results indicate that this approach can identify interactions among individual differences that are variably associated with relapse rates. Identification of relapse subgroups may have important implications for both theories and treatment of smoking relapse.

Adult↗
PubMed1993

Cardiovascular reactivity as a predictor of relapse in male and female smokers.

This study examined the role of psychophysiological reactivity to general stressors measured before smoking cessation as a predictor of relapse in individuals who quit for a minimum of 12 hr and were then followed for a 12-month interval. The study group consisted of 132 (56.9%) female and 100 (43.1%) male participants in a formal smoking cessation program. The reactivity measures were taken while the Ss were still smoking. Heart rate and blood pressure measurements were taken while Ss were resting, performing mental arithmetic, and delivering a speech and after Ss had been standing for 2 min. In the sample as a whole and for women, a higher level of systolic blood pressure reactivity to the cognitive challenge was associated with a shorter time to relapse (p < .05). In men, greater systolic blood pressure decline to standing was significantly associated with a shorter time to relapse (p < .05).

Adult↗
PubMedDate not supplied

Abstinence effects as predictors of 28-day relapse in smokers.

The present analysis sought to determine the relationship between abstinence effects in 64 ex-smokers (mean age = 41.1 years) and the rate at which they relapsed over 4 weeks of biochemically confirmed follow-up. This analysis focused on six abstinence effects that play a central role in the DSM-III-R and DSM IV definitions of withdrawal from nicotine: anger, depression, craving, appetite, confusion, and tension. Significant increases were observed for all six symptoms following cessation, and, with the exception of craving, substantial intercorrelations among the abstinence effects were noted. Cox proportional hazards survival models identified increases in anger, depressed mood, and craving to be significantly associated with a shorter time to relapse (all p < .03). Stepwise Cox proportional hazards survival analysis identified increases in depressed mood and craving as the most significant combination of abstinence effects in relation to time to relapse. A more stringent test of the potency of the relationship between these abstinence effects and time to relapse was conducted in which two other risk factors in this sample, method of quitting and education level, were also included in the model testing sequence. Even after adjustment for these significant risk factors, the increase in craving remained a significant predictor of a higher rate of relapse. This result suggests a robustness to this particular abstinence effect as a determinant of the speed with which ex-smokers relapse over a 1-month interval after cessation.

Adult↗
PubMedDate not supplied

Self-reported abstinence effects in the first month after smoking cessation.

The present study evaluated self-reported subjective complaints (29 single items and 11 scales) at precessation, on quit day, and on Days 1, 2, 3, 7, 14, 21, and 28 after cessation in 46 healthy quitters who remained abstinent for the first month after cessation (biochemically confirmed). Also tested on the same schedule were 29 nonsmokers matched for age and gender. Specific criteria were set for transient and offset effects based on the direction, magnitude, and time course of changes in symptoms after cessation. Results indicated that single-item anger, anxiety, depression, difficulty concentrating, irritability, restlessness, dizziness, and nausea, and the Shiffman-Jarvik Stimulation/Sedation Subscale, the Perceived Stress scale, and the POMS anger, confusion, and tension subscales met the criteria for transient effects, and that single-item desire to smoke, cough, and headache, and the Shiffman-Jarvik Psychological Subscale met the criteria for offset effects. These findings help to clarify which subjective complaints after smoking cessation are transient effects and which are offset effects, a distinction with important implications for understanding nicotine dependence and for designing pharmacological and nonpharmacological interventions for smoking cessation.

Adult↗
PubMedDate not supplied

Relationship of family history scores for stroke and hypertension to quantitative measures of white-matter hyperintensities and stroke volume in elderly males.

White-matter hyperintensities (WMHI) are frequently associated with cerebrovascular risk factors in the elderly, particularly hypertension, and have been interpreted as a subclinical form of ischemic brain damage. WMHI, clinical stroke and blood pressures show significant genetic influences. The objective of this study was to determine whether a relationship exists between family history of stroke and/or hypertension in first degree relatives and WMHI in the elderly. WMHI and stroke (CVA) volumes were quantified from brain MRI performed on 414 white, male twins born between 1917 and 1927 (average age 72.3 +/- 2.9 years). WMHI, adjusted for age and head size, was significantly correlated with the family history score (r = 0.21, p < 0.001). Dividing the family history scores into quintiles revealed significant differences in WMHI by quintile mean (p < 0.05). Subjects in the highest quintile of family history score had the highest mean WMHI. Recalculation of the family history score, by only counting relatives reported to have had a clinical stroke as a positive event, revealed a nonsignificant correlation with WMHI, but the correlation of the family history score with MRI CVA volume was significant (p < 0.05). Stepwise multivariate analysis including ApoE status, current smoking status, smoking packyear history, Doppler ankle/arm blood pressure ratios, current and long term hypertensive status and current systolic and diastolic pressures indicated that the stroke/hypertension family history score was the single best predictor (p < 0.01) of WMHI volumes. Family history was not an independent predictor of CVA volume.

Aged↗