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.

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.

Delayed onset of Alzheimer's disease with nonsteroidal anti-inflammatory and histamine H2 blocking drugs.

Factors that modify onset of Alzheimer's disease (AD) may be revealed by comparing environmental exposures in affected and unaffected members of discordant twin pairs or sibships. Among siblings at high risk of AD, sustained use of nonsteroidal anti-inflammatory drugs (NSAIDs) was associated with delayed onset and reduced risk of AD. After adjustment for use of NSAIDs, there was minimal effect on onset with reported history of any of three common illnesses (arthritis, diabetes, or acid-peptic disease). However, independent of exposure to NSAIDs, onset was unexpectedly delayed in those reporting extended use of histamine H2 blocking drugs. Randomized clinical trials will be needed to affirm the utility of these drugs for prevention, but the present findings may have implications for pathogenesis: because NSAIDs block the calcium-dependent postsynaptic cascade that induces excitotoxic cell death in NMDA-reactive neurons, and because histamine potentiates such events, excitotoxicity may deserve additional investigation in AD.

Modulated kinase activities in cells undergoing tumour necrosis factor-induced apoptotic cell death.

Tumour necrosis factor-alpha (TNF) has a variety of cellular effects including apoptotic and necrotic cytotoxicity. TNF activates a range of kinases, but their role in cytotoxic mechanisms is unclear. HeLa cells expressing elevated type II 75 kDa TNF receptor (TNFR2) protein, analysed by flow cytometry and Western analysis, showed altered c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38MAPK; but not MAPK) protein content and activation. There was greater JNK activation, but reduced p38MAPK activation in dying cells compared to those still to enter TNF-induced apoptosis. Moreover, cells displaying more rapid apoptosis possess higher levels of type I 55 kDa TNFR1 receptor isoform, but less TNFR2. These findings reveal differential kinase activation in TNF-induced apoptotic death.

Dysphagia following brain-stem stroke. Clinical correlates and outcome.

We studied 23 individuals (16 men, seven women; mean age 57 years) who had brainstem strokes confirmed by computed tomography of the head or magnetic resonance imaging. Videofluoroscopic modified barium-swallowing examination showed aspiration in 15 of 23 patients. Of the 15 aspirating patients, the majority had bilateral strokes with multiple lesion loci, most often in association with large-vessel disease. All 15 patients had involvement of the pons or medulla. Statistical analyses revealed a significant association between aspiration and pharyngeal residue observed under videofluoroscopy, cranial nerve IX abnormality, vocal fold weakness, and severe dysarthria. Despite initial severity, recovery was good. Following an aggressive program of aspiration prevention, over 80% of patients resumed full oral nutrition at the last follow-up.

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.

Early-onset Alzheimer's disease: clinical predictors of institutionalization and death.

Follow-up observations were made of 92 white patients with early-onset Alzheimer's disease to determine the demographic, clinical, and neuropsychological factors predictive of institutionalization or death. The cumulative mortality rate 5 years after entry into the study was 23.9%, compared with an expected rate of 9.5%. The 5-year cumulative rate of admission to nursing homes was 62.8%. The language ability of the patients on entry to the study, their scores on a brief screening test of cognitive function, and their overall ratings of clinical dementia were found to be predictors of subsequent institutional care and death. The age of the patients had a significant modifying effect on these predictive factors, resulting in a greater risk of institutionalization and death in younger patients with severe cognitive impairment as compared with older individuals with the same degree of dysfunction.

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.

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.

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.

Documented head injury in early adulthood and risk of Alzheimer's disease and other dementias.

BACKGROUND: The association between antecedent head injury and AD is inconsistent. OBJECTIVE: To examine the association between early adult head injury, as documented by military hospital records, and dementia in late life; and to evaluate the interaction between head injury and APOE epsilon4 as risk factors for dementia. METHODS: The study had a population-based prospective historical cohort design. It included men who were World War II Navy and Marine veterans, and were hospitalized during their military service with a diagnosis of either a nonpenetrating head injury or another unrelated condition. In 1996 to 1997, military medical records were abstracted to document the occurrence and details of closed head injury. The entire sample was then evaluated for dementia and AD using a multistage procedure. There were 548 veterans with head injury and 1228 without head injury who completed all assigned stages of the study. The authors estimated risk of dementia, specifically AD, using proportional hazards models. RESULTS: Both moderate head injury (hazard ratio [HR] = 2.32; CI = 1.04 to 5.17) and severe head injury (HR = 4.51; CI = 1.77 to 11.47) were associated with increased risk of AD. Results were similar for dementia in general. The results for mild head injury were inconclusive. When the authors stratified by the number of APOE epsilon4 alleles, they observed a nonsignificant trend toward a stronger association between AD and head injury in men with more epsilon4 alleles. CONCLUSIONS: Moderate and severe head injuries in young men may be associated with increased risk of AD and other dementias in late life. However, the authors cannot exclude the possibility that other unmeasured factors may be influencing this association.

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.

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.

Extravascular extravasation of radiographic contrast media. Effects of conventional and low-osmolar agents in the rat thigh.

We compared the damage resulting from intradermal injection of four commonly used radiographic contrast media in laboratory rats. Sixty percent meglumine diatrizoate (Reno M 60) and ioxaglate (Hexabrix) produced significantly more ulceration and crusting on gross inspection and more necrosis, edema, and hemorrhage on histologic evaluation than iopamidol 300 (Isovue) or 0.9% (normal) saline. Thirty percent meglumine diatrizoate (Reno M Dip) had an intermediate toxicity, resulting in significantly more visible swelling and more microscopically detected hemorrhage than iopamidol or saline, but less ulceration/crusting and necrosis than Reno M 60 and ioxaglate. Since the three contrast agents of similar osmolality produced different degrees of tissue damage, our results suggest that factors other than high osmolality are partially responsible for determining the severity of injuries from extravasated contrast media.

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.

Changing rates of cesarean delivery: the Duke experience, 1978-1986.

There was a steady increase in the yearly cesarean delivery rate, from 14.0 to 24.8%, between July 1, 1978 and June 30, 1986 at Duke University Medical Center; this was associated predominantly with an increase in the rate of primary cesarean deliveries. The three most frequent major diagnoses associated with primary cesarean delivery changed significantly over the study period. Fetal compromise became the most commonly associated diagnosis (from third), dystocia second (from first), and maternal disease third (from second). The categories of fetal positional abnormalities (fourth), abnormalities of placentation (fifth), and multiple pregnancy (sixth) did not change in rank. Primary cesarean delivery patients were compared with patients who delivered vaginally using odds ratios, prevalence, and population-attributable fractions. The risk factors of nulliparity, gestational age less than 37 weeks, late decelerations, and referral had the largest impact on the primary cesarean rate. Decreases in rates related to an increased tolerance of abnormalities of labor were overshadowed by the effects of increased concerns related to fetal health.

Ambulatory cardiovascular activity in Vietnam combat veterans with and without posttraumatic stress disorder.

The present study investigated the relationship between daily diary affect ratings and ambulatory cardiovascular activity in 117 male Vietnam combat veterans (61 with posttraumatic stress disorder [PTSD] and 56 without PTSD). Participants completed 12-14 hr of ambulatory monitoring and daily diary affect ratings. Compared with veterans without PTSD, veterans with PTSD reported higher negative affect and lower positive affect in daily diary ratings. No differences were detected for mean laboratory initial recordings or mean ambulatory heart rate (HR), systolic blood pressure (SBP), or diastolic blood pressure (DBP). However, compared with veterans without PTSD, veterans with PTSD demonstrated higher SBP and DBP variability and a higher proportion of HR activity (compared with initial recording values) during daily activity. There was a significant Time of Day x Group interaction for mean HR, with a trend for PTSD participants to maintain HR levels during evening hours.

A longitudinal study of gender differences in depressive symptoms from age 50 to 80.

The Obvious Depression Scale was administered to 739 community residents at ages 50, 60, and 80 years, with 151 present at all waves. Although selective attrition influenced the level of depressive symptoms in cross-sectional vs. longitudinal samples, both sets of analyses revealed higher scores in women than in men at ages 50 and 60, but not at age 80. Men showed increases in depressive symptoms from age 60 to 80, but women did not (interaction p < .002). This interaction was not present in somatic symptoms, which increased across time in both genders. Potential explanations include differential changes in social roles with aging.

Cytomegalovirus infection and chronic hemodialysis.

Serologic and virologic studies of cytomegalovirus (CMV), a virus infection often disseminated in immunosuppressed patients, were initiated among hemodialysis patients, home dialysis partners, hemodialysis center personnel, and several groups of patients. No evidence was found of activation or persistence of CMV infections in connection with chronic renal disease or in association with hemodialysis. Evidence of increased CMV activation and/or infection was found among individuals who had re-entered the dialysis program following renal allograft rejection. The data indicate that dialysis personnel and home dialysis partners are not at increased risk for CMV infection. The findings of this study, which contrast with those pertaining to hepatitis B infection, suggest that different mechanisms are responsible for establishing both infection and persistence of CMV and hepatitis B.

Occupational characteristics and cognitive performance among elderly male twins.

OBJECTIVE: To examine the effect of occupational characteristics on cognitive status change in members of the NAS-NRC Twins Registry of World War II veterans. METHODS: Participants completed the modified Telephone Interview for Cognitive Status (TICS-m) on three occasions spanning a period of approximately 7 years. Based on factor analysis, occupational characteristics were interpreted as reflecting general intellectual demands (GI), human interaction and communication (HC), physical exertion (PE), and visual attention (VA). RESULTS: Based on regression analysis of TICS-m change that was dependent on twin pairing and additionally covarying for education, age at each testing event, medical conditions, and initial TICS-m score, higher GI was associated with a modest longitudinal improvement in TICS-m performance, whereas higher PE and VA were both associated with a modest decline. Subsequent analysis revealed that these significant effects were present among dizygotic twins, but not among monozygotic twins. CONCLUSIONS: Previous findings of a relationship between occupational characteristics and cognitive performance in later life may be partially explained by genetic factors; however, until these genes are identified, occupational characteristics may be useful markers.