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Biomedical subjects

M J Helms

Publications and source records attributed to M J Helms.

At least 19 recordsLinked to original sources

APOE and AD concordance in twin pairs as predictors of AD in first-degree relatives.

OBJECTIVE: To examine the independent effects of the APOE genotype (APOE) and concordance for AD in twin pairs on the occurrence of AD in first-degree relatives. BACKGROUND: Studies of twins have been undertaken to investigate the influence of genes in a variety of conditions, including AD. A previous study, performed before reports linking APOE to AD, demonstrated an increase in AD among first-degree relatives of twins concordant for AD compared with relatives of discordant twins. METHODS: In a sample of 94 twin pairs the authors examined the association between concordance for AD within the twin pair and family history of AD among first-degree relatives of twins. They then examined the extent to which the presence of the APOE epsilon4 allele in the twin pair explains the association between concordance for AD within the twin pair and family history of AD. RESULTS: Concordance among twins was associated with increased risk of AD among relatives (logrank test, chi2 = 12.558; p = 0.0004), and the presence of at least one APOE epsilon4 allele in each member of the twin pair is also associated with increased risk of AD among family members (logrank test, chi2 = 7.712; p = 0.0055). CONCLUSIONS: APOE genotype explains much but not all of the association between concordance among twins and increased familial risk of AD.

Age of Onset

Cerebrovascular disease and depression symptoms in the cardiovascular health study.

BACKGROUND AND PURPOSE: Evidence is mounting linking cerebrovascular disease with depressive symptoms in the elderly. Lesions in both white and gray matter have been associated with depressive symptoms and major depression. We sought to investigate the relationship between depressive symptoms and white and gray matter lesions in subjects participating in the Cardiovascular Health Study. METHODS: In a sample of 3660 men and women who underwent a standardized interview, physical examination, and MRI scan, we examined the association between number of white and gray matter lesions and white matter grade (a measure of severity) and reported depressive symptoms using a modified version of the Centers for Epidemiologic Studies Depression (CES-D) scale. We controlled for a variety of demographic and medical variables as well as functional status and Modified Mini-Mental State Examination score. RESULTS: The number of small (<3 mm) basal ganglia lesions was significantly associated with reported depressive symptoms, but white matter grade was not. In subsequent logistic regression models, number of basal ganglia lesions remained a significant predictor after controlling for non-MRI variables and severity of white matter lesions. CONCLUSIONS: Our findings extend previous reports that linked cerebrovascular changes to depressive symptoms in clinical populations to a large community-based population. This report provides further evidence of the importance of basal ganglia lesions in geriatric depression.

Activities of Daily Living

Measures of hostility as predictors of facial affect during social interaction: evidence for construct validity.

We assessed the construct validity of several self-report measures and an interview-based measure of hostility (Interpersonal Hostility Assessment Technique [IHAT]) by evaluating their associations with a behavioral indicator of hostile emotions (facial expressions during social interaction). Participants in the study were 123 volunteers (44% males and 56% females) who were recruited from local community organizations. Self-report measures (Cook-Medley Hostility Scale, Rotter Interpersonal Trust Scale, Buss-Durkee Hostility Inventory, and Spielberger Anger Expression Scale) were represented by factor scores reflecting Overt Hostility, Covert Hostility, and Hostile Beliefs. A canonical correlation analysis identified significant associations between a set of facial affect scores reflecting animosity and various measures of hostility. Specifically, increases in anger and disgust expressions and decreases in happy facial expressions were associated with high IHAT scores and high scores on self-report measures of Hostile Beliefs and Covert Hostility. Women were more expressive than men, especially concerning positive affect, and women had lower scores on self-report measures of Hostile Beliefs and Overt Hostility. IHAT scores were uncorrelated with any of the self-report factors which suggests the two assessment techniques are tapping different aspects of the hostility construct.

Adult

Symptoms of depression and changes in body weight from adolescence to mid-life.

OBJECTIVE: To investigate the relationship of symptoms of depression to weight changes in healthy individuals of normal weight across a follow-up of over 20 y. PARTICIPANTS AND DESIGN: College students (3885 men and 841 women) were administered a self-report depression measure in the mid-1960s. Their baseline body mass index (BMI) was calculated from their college medical records. Participants were contacted by mail in the late 1980s and asked to report their current height and weight as well as their smoking and exercise habits. Another measure of depressive symptoms was obtained from 3560 individuals at follow-up. Multiple regression models were used to relate changes in weight to depression scores while controlling for background (gender, baseline BMI and the gender by BMI interaction) and behavioral (exercise and smoking) predictors. RESULTS: The relationship between depressive symptoms and body weight change took the form of an interaction with baseline BMI (P < 0.001). Those with high baseline depression scores gained less weight than their nondepressed counterparts if they were initially lean, but more if they were initially heavy. This trend was especially strong in those with high depression scores at both baseline and follow-up. CONCLUSIONS: The findings support the hypothesis that depression exaggerates pre-existing weight change tendencies. This pattern would not have been detected by an examination of main effects alone, illustrating the need to move toward more complicated interactive models in the study of psychological factors and weight.

Adolescent

A twin study of late-onset depression and apolipoprotein E epsilon 4 as risk factors for Alzheimer's disease.

A prior history of depression and the epsilon 4 allele of apolipoprotein E (APOE) have each been associated with development of Alzheimer's disease (AD). In a sample of 142 elderly twins from a large study of dementia, we examined the relation of major depression, APOE genotype and AD using time-dependent proportional hazards models. Compared against the risk for AD with no history of depression and no epsilon 4 allele, the risk ratio for AD with two epsilon 4 alleles was 2.87 (C.I. = 1.56-5.28), with one epsilon 4 allele, 1.82 (C.I. = 1.09-3.04) and with late-onset depression and no epsilon 4 allele, 2.95 (C.I. = 1.55-5.62). There was no suggestion of an interaction between prior depression and APOE genotype in their effects on AD risk. Results were similar when the sample was stratified by twin pair, so that a single genetic marker is unlikely to explain the relation among depression, APOE, and dementia. Risk ratios declined substantially with increasing intervals between the onset of depression and AD. Thus, for many individuals, the association of depression and AD may reflect the occurrence of prodromal depressive symptoms rather than a true risk relationship.

Age of Onset

Psychosocial correlates of job strain in a sample of working women.

BACKGROUND: This study identifies potential mediators of job strain effects on health by determining whether psychosocial factors known to predict an increased risk of cardiovascular disease and all-cause mortality are higher among women who report high levels of job strain. METHODS: Measures of job strain and other psychosocial risk factors were obtained in a sample of 152 female employees of a local corporation. Canonical correlation and analyses of covariance were used to assess relationships between job demands and decision latitude and other psychosocial risk factors. RESULTS: A significant (P = .002) solution to the canonical correlation analysis showed that high job demands and low decision latitude were correlated with a pattern of psychosocial factors consisting of (1) increased levels of negative emotions like anxiety, anger, depression, and hostility; (2) reduced levels of social support; and (3) a preponderance of negative compared with positive feelings in dealings with coworkers and supervisors. This pattern was confirmed by analyses of covariance that adjusted for demographic and specific job characteristics. CONCLUSIONS: The canonical correlation analysis results provide empirical support for the job strain construct. The most important finding is that health-damaging psychosocial factors like job strain, depression, hostility, anxiety, and social isolation tend to cluster in certain individuals.

Adult

Are SSRIs better than TCAs? Comparison of SSRIs and TCAs: a meta-analysis.

In this analysis we examined studies of tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs) to compare efficacy and drop-out rates. Frequency of reported side effects was also studied. Using Medline, we located 36 clinical trials of TCAs and SSRIs in a double-blind comparison. We performed a meta-analysis on these studies and on a subgroup of 21 studies that had more uniformly defined outcome criteria. The main outcome measures were efficacy for treatment completers and for the intention-to-treat group; drop-out rates due to adverse reactions and lack of efficacy; and reported side effects. Overall, the response rate to treatment for patients who completed a trial was 63.2% for SSRIs and 68.2% for TCAs (P = 0.038). For the intention-to-treat groups, these rates dropped to 48.0 and 48.6% (P, NS), respectively. Significantly more TCA-treated than SSRI-treated subjects dropped out due to either lack of efficacy or adverse reactions (30.0 vs. 24.7%, P = 0.01). Patients taking SSRIs experienced significantly more gastrointestinal problems and sexual dysfunction, whereas treatment with TCAs produced significantly more complaints of sedation, dizziness, and anticholinergic symptoms.

Antidepressive Agents, Tricyclic

Apolipoprotein E epsilon 4 allele and hippocampal volume in twins with normal cognition.

We examined the relation of APOE-epsilon 4, hippocampal volume, and cognitive performance in ten pairs of cognitively normal twins who had a mean age of 62.5 years (SD = 7.8). There were no significant differences in neuropsychological measures of the groups categorized by the presence of an epsilon 4 allele. However, the mean normalized right and left hippocampal volumes were smaller in the epsilon 4 groups compared to the group without epsilon 4. Combined with prior reports, these findings suggest that epsilon 4 is associated with differences in brain morphology that may be evident when no symptoms of dementia are present.

Alleles

Personality factors differentially predict exercise behavior in men and women.

Personality assessed with the Minnesota Multiphasic Personality Inventory (MMPI) in college was used to predict exercise behavior measured at midlife in 3,630 men and 796 women enrolled in the University of North Carolina Alumni Heart Study. Logistic regression models were fitted for each of the MMPI clinical scales to test the predictive effect of personality, gender, and their interaction on adult exercise behavior. Lower depression, social introversion, and psychopathic deviance scores were associated with increased probability of exercising in midlife for both men and women. Furthermore, better psychological health (indexed by lower hypochondriases and psychasthenia) in college was generally predictive of increased exercise for men, whereas higher scores on these same factors predicted midlife exercise for women. There were two other patterns of gender interactions: (a) for men, lower scores on hysteria and schizophrenia scales were associated with increased probability of exercising at midlife, whereas these factors were unrelated to exercise for women and (b) for women, lower ego strength and higher college scores on paranoia and mania were associated with exercise behavior at midlife. These data suggest that early adulthood personality predictors of exercise behavior at midlife are both gender-neutral and gender-specific; that is, where no gender differences exist, healthier personality traits predict exercise at midlife, and when gender differences do occur, healthier college patterns of personality predict exercise behavior for men and sedentary behavior for women.

Adolescent

Depression and long-term mortality risk in patients with coronary artery disease.

Previous research has established that patients with coronary artery disease (CAD) have an increased risk of death if they are depressed at the time of hospitalization. Follow-up periods have been short in these studies; therefore, the present investigation examined this phenomenon over an extended period of time. Patients with established CAD (n = 1,250) were assessed for depression with the Zung Self-Rating Depression Scale (SDS) and followed for subsequent mortality. Follow-up ranged up to 19.4 years. SDS scores were associated with increased risk of subsequent cardiac death (p = 0.002) and total mortality (p < 0.001) after controlling for initial disease severity and treatment. Patients with moderate to severe depression had a 69% greater odds of cardiac death and a 78% greater odds of mortality from all causes than nondepressed patients. Increased risk was not confined to the initial months after hospitalization. Patients with high SDS scores at baseline still had a higher risk of cardiac death > 5 years later (p < 0.005). Compared with the nondepressed, patients with moderate to severe depression had an 84% greater risk 5 to 10 years later and a 72% greater risk after > 10 years. Patients with mild depression had intermediate levels of risk in all models. The heightened long-term risk of depressed patients suggests that depression may be persistent or frequently recurrent in CAD patients and is associated with CAD progression, triggering of acute events, or both.

Coronary Disease

Interpersonal and self-reported hostility among combat veterans with and without posttraumatic stress disorder.

The present study investigated self-reported and interpersonal hostility in 70 Vietnam combat veterans with and without posttraumatic stress disorder (PTSD) and 60 comparison community volunteer subjects. Veterans were 50 help-seeking, male Vietnam combat veterans with PTSD and 20 non-help-seeking male combat veterans without PTSD. Vietnam veterans with PTSD not only reported more hostility than non-PTSD veterans and healthy community volunteers, but also reacted behaviorally with more hostility during an interpersonal interaction. Compared to veterans without PTSD, veterans with PTSD reported significantly higher levels of hostility and demonstrated significantly greater non-verbal expressions of hostility during an interpersonal task. These results suggest that the level of hostility in PTSD combat veterans may be high as compared to comparison groups. The implications of these results and possible research directions are presented.

Case-Control Studies

Alzheimer's disease in the National Academy of Sciences-National Research Council Registry of Aging Twin Veterans. III. Detection of cases, longitudinal results, and observations on twin concordance.

OBJECTIVES: To detect cases of Alzheimer's disease (AD) in a large population of twins living throughout the United States and to examine concordance for AD in twins as a function of age and genotype for apolipoprotein E (APOE). SETTING: Nationwide survey. DESIGN: Multistage screening and field evaluation beginning with two telephone interviews and culminating with laboratory tests, longitudinal neuropsychological measures, physician examination, and diagnostic consensus among experts. PARTICIPANTS: Membership in 1990-1991 of intact pairs in the National Academy of Sciences--National Research Council Registry of veteran twins, then aged 62 to 73 years. MAIN OUTCOME MEASURES: Completeness of case detection was examined in collateral studies. Zygosity and APOE genotypes were determined by restriction mapping. Concordance was calculated by the proband method. RESULTS: Ninety subjects who screened positively for AD were studied in person, and 60 whose differential diagnoses included AD were followed up, as were their co-twins. Sensitivity of screening was estimated at greater than 99%, but 24% of subjects refused participation after initial screening. Seven of 38 diagnoses of AD have been confirmed at autopsy, and 31 other subjects eventually met criteria for probable or possible AD (prevalence estimate, 0.42%, 95% confidence interval, 0.29% to 0.56%), with good interrater reliability (intraclass r = .86). Excluding one discordant pair with unknown zygosity, concordance rates were 21.1% (4/19) for monozygotic and 11.1% (2/18) for dizygotic probands. Concordance was 50% for twins sharing the epsilon 4/epsilon 4 genotype at APOE, but there were no affected co-twins of 15 probands with onset before age 70 years, no epsilon 4 allele, and no family history of AD. The mean (SD) period of discordance in the latter pairs was 11.3 (3.3) years. CONCLUSIONS: The multistage case-detection approach achieved reliable and valid diagnoses of AD with high apparent sensitivity but substantial attrition after initial screening. Genetic influences in AD at this age are limited, except among homozygotes for allele epsilon 4 at APOE. Subjects with early-onset AD who lack the epsilon 4 allele are not rare, and their condition appears to have little genetic influence. They should be ideal for studies on environmental cause of AD.

Aged

Are vaginal and rectal pressures equivalent approximations of one another for the purpose of performing subtracted cystometry?

OBJECTIVE: To determine if rectal and vaginal pressures are clinically equivalent to one another for the purpose of calculating subtracted detrusor pressure during routine filling cystometry and pressure-flow voiding studies. METHODS: A total of 140 consecutive filling and voiding cystometrograms were performed at separate sessions on 127 female patients undergoing routine clinical cystometry for a variety of clinical indications, usually urinary incontinence. In all cases, intravaginal as well as intrarectal pressures were measured simultaneously using microtip transducer pressure catheters, and two subtracted detrusor pressures were calculated throughout each study. Rectal and vaginal pressure measurements from the same patient were compared with the patient in the supine position with an empty bladder, in the erect position with a full bladder, and in the sitting position during voiding at the point of maximum urinary flow. RESULTS: The mean pressures were similar in all cases. Although there was no statistical difference in the mean differences between the rectal and vaginal pressures in the supine-empty position (P = .5528), significant differences were noted between them in the erect-full and sitting-voiding positions (P = .0016 and P = .0033, respectively). Linear regression analysis of the data obtained in each position was carried out, plotting vaginal pressure on the x axis and rectal pressure on the y axis. The corresponding r values for each position were 0.431 for the supine-empty position, 0.547 for the erect-full position, and 0.478 for the sitting-voiding position, indicating poor correlation between pressures in individual patients. In nine patients (6.5%) with significant vaginal relaxation and large cystoceles, a steady rise in vaginal pressure was noted during bladder filling. In six patients (4.4%), one or more spontaneous vaginal contractions were noted during the course of the study, whereas in 68 (48.9%), spontaneous rectal contractions were present. Of the 68 cases where spontaneous rectal contractions were noted, these contractions faded away in 53 cases (77.9%) as the study progressed. CONCLUSIONS: Rectal pressure and vaginal pressure are not the same during filling and voiding cystometry. Although they are reasonable approximations of each other for most qualitative clinical diagnostic purposes, potentially significant differences in subtracted detrusor pressure may occur, depending on which pressure is used as the approximation of intra-abdominal pressure. This may affect clinical management decisions in individual patients. The technique used for approximating abdominal pressure must be stated clearly in any report or publication dealing with subtracted cystometry.

Adult

Inverse association of anti-inflammatory treatments and Alzheimer's disease: initial results of a co-twin control study.

We conducted a co-twin control study among 50 elderly twin pairs with onsets of Alzheimer's disease (AD) separated by 3 or more years. Twenty-three male pairs (46%) were screened from the (U.S.) National Academy of Sciences-National Research Council Registry (NAS-NRC Registry) of World War II veteran twins; others (mostly women) had responded to advertisements or were referred from AD clinics. Twenty-six pairs (52%) were monozygous. The onset of AD was inversely associated with prior use of corticosteroids or ACTH (odds ratio [OR], 0.25; 95% confidence interval [CI], 0.06 to 0.95; p = 0.04). Similar but weaker trends were present among pairs discordant for history of arthritis or for prior daily use of nonsteroidal anti-inflammatory drugs (NSAIDs) or aspirin. The association was strongest when we combined use of steroids/ACTH or NSAIDs post hoc into a single variable of anti-inflammatory drugs (AIs) (OR, 0.24; CI, 0.07 to 0.74; p = 0.01). The inverse relation was strong in female (volunteer) twin pairs but was not present in the younger men from the NAS-NRC Registry. AIs had typically been taken for arthritis or related conditions, but a similar result was apparent after controlling statistically for the arthritis variable (OR, 0.08; CI, 0.01 to 0.69; p = 0.02). AIs have been proposed as a means of retarding the progression of AD symptoms, and these data suggest that AIs may also prevent or delay the initial onset of AD symptoms. Because of limitations in the case-control method, our results require corroboration with hypothesis-driven research designed to control bias and confounding.

Age Factors

Normal values for single exhalation diffusing capacity and pulmonary capillary blood flow in sitting, supine positions, and during mild exercise.

Previous approaches to the measurements of pulmonary diffusing capacity (DL) and pulmonary capillary blood flow (QC) utilized either the rebreathing or the single inhalation technique in conjunction with radioisotope gas and mass spectrometry. In the present study, we utilized a newly developed rapid infrared analyzer in conjunction with the slow single exhalation technique on 100 healthy volunteers to establish normal values for DL and QC under sitting, supine, and exercise conditions. The exercise level was determined by a target heart rate: HRex = ([HRmax - HRrest]/3) + HRrest. Prediction equations based on regressions on age, sex, height, or weight were then computed for sitting, supine, and exercise values. We found that mean DL and QC increased by approximately 12 percent and 8 percent, respectively, from sitting to supine posture, and by approximately 30 percent and 100 percent, respectively, from sitting (rest) to mild exercise. These results provided a database for further studies in the single exhalation method in various clinical settings.

Acetylene

Dose response relationship between plasma ACTH and cortisol after the infusion of ACTH1-24.

The authors examined the dose response relationship between plasma ACTH and cortisol concentrations after the administration of various doses of ACTH1-24 (0.025 micrograms, 0.125 micrograms, 0.25 micrograms, 1 microgram, 250 micrograms) in dexamethasone-suppressed normal volunteers. A logarithmic dose-response relationship between the dose of ACTH administered and plasma cortisol concentration was found. Although there was considerable variability in plasma ACTH concentrations, there was, however, a definite correlation between area under the curve for ACTH and area under the curve for cortisol after the various doses of ACTH.

Adrenocorticotropic Hormone

Acute childbirth morbidity: its measurement using hospital charges.

OBJECTIVES: An analytic descriptive analysis of acute childbirth morbidity was carried out at Duke University Medical Center, comparing patients delivered by primary cesarean section with those delivered vaginally. STUDY DESIGN: All primary cesarean deliveries and vaginal deliveries from July 1, 1981, through June 30, 1986, were combined with maternal and infant charge data. A total of 7256 patients were analyzed. A description of the charges for the associated diagnoses was carried out. A morbidity index was used to identify differences in predicted median hospital charges with 95% confidence intervals. RESULTS: The ratio of mean primary cesarean delivery to mean vaginal delivery total charges was 2.5:1. The magnitude of the mean hospital charges was inversely related to the frequency of the indication with the lowest charges associated with dystocia and the highest with multiple pregnancy. Antepartum risk factors (increased maternal age, patient referral) were associated with increases in maternal and infant morbidity as measured by the morbidity index. Chronic maternal hypertension resulted in decreased maternal morbidity but increased infant morbidity when primary cesarean delivery was used. Although preterm delivery was associated with large increases in charges, it was not significantly altered by using primary cesarean delivery. Risk factors associated with the management of abnormalities of labor were associated with decreases in maternal and infant morbidity when primary cesarean delivery was used. CONCLUSION: Analysis of acute childbirth morbidity, as measured by hospital charges, showed marked variation of diagnosis and risk-specific charges for patients delivered by primary cesarean section.

Adult