Spousal caregivers of dementia victims: longitudinal changes in immunity and health.

Providing long-term care for a demented relative profoundly affects caregivers' lives. We assessed changes in depression, immune function, and health in 69 spousal caregivers who had already been caregiving for an average of five years and 69 sociodemographically matched control subjects. Between the initial sample ("intake") and the follow-up data collected an average of 13 months later, caregivers showed decrements relative to controls on three measures of cellular immunity. Caregivers also reported significantly more days of infectious illness, primarily upper respiratory tract infections. Caregivers had a much greater incidence of depressive disorders than controls, with 25% of caregivers meeting syndromal criteria at intake and 32% at follow-up, compared with no cases among controls at intake and 6% at follow-up. Caregivers who reported lower levels of social support at intake and who were most distressed by dementia-related behaviors showed the greatest and most uniformly negative changes in immune function at follow-up.

Decision-oriented test request forms. A system for implementing practice parameters in laboratory medicine.

The implementation of practice parameters in laboratory medicine by changing physicians' behavior represents a major challenge. Education, restriction of tests, financial incentives, and concurrent chart reviews have not been effective in persuading physicians to improve their use of laboratory tests. The use of decision-oriented test request forms is suggested as an approach to this problem.

Marital discord and immunity in males.

While limited data suggest significant gender differences in mental and physical health risks following marital disruption, men have not been studied as intensively as women. In this study, self-report data and blood samples were obtained from 32 separated or divorced men and 32 sociodemographically matched married men. Separated/divorced men were more distressed and lonelier, and reported significantly more recent illness than did married men; the former also had significantly poorer values on two functional indices of immunity (antibody titers to two herpesviruses), while not differing significantly on quantitative indices (percentages of helper and suppressor cells and their ratio). Among married men, poorer marital quality was associated with greater distress and a poorer response on one functional immunological measure, antibody to Epstein-Barr virus (EBV), as well as lower helper/suppressor ratios. Among separated/divorced subjects, those who had separated within the past year and who had initiated the separation were less distressed, reported better health, and had a better performance on one functional immunological assay (EBV antibody titers) than did noninitiators. These data are discussed in the context of research on longer-term adaptation to marital disruption.

Chronic stress and immunity in family caregivers of Alzheimer's disease victims.

Although acute stress has been associated with transient immunosuppression, little is known about the immunologic consequences of chronic stress in humans. In order to investigate possible health-related consequences of a long-term stressor, we obtained blood samples for immunologic and nutritional analyses and psychologic data from 34 family caregivers of Alzheimer's disease (AD) victims and 34 sociodemographically matched comparison subjects. Family caregivers for AD victims were more distressed than comparison subjects without similar responsibilities. Greater impairment in the AD victim was associated with greater distress and loneliness in caregivers. Caregivers had significantly lower percentages of total T lymphocytes and helper T lymphocytes than did comparison subjects, as well as significantly lower helper-suppressor cell ratios; caregivers also had significantly higher antibody titers to Epstein-Barr virus than did comparison subjects, presumably reflecting poorer cellular immune system control of the latent virus in caregivers. The percentages of natural killer cells and suppressor T lymphocytes did not differ significantly. These data suggest that chronically stressed AD family caregivers do not show immunologic or psychologic adaptation to the level of their well-matched age peers.

Marital quality, marital disruption, and immune function.

Marital disruption is associated with significant increases in a variety of psychologic and physical disorders. In order to examine psychologic and physiologic mediators, self-report data and blood samples were obtained from 38 married women and 38 separated/divorced women. Among married subjects, poorer marital quality was associated with greater depression and a poorer response on three qualitative measures of immune function. Women who had been separated 1 year or less had significantly poorer qualitative and quantitative immune function than their sociodemographically matched married counterparts. Among the separated/divorced cohort, shorter separation periods and greater attachment to the (ex)husband were associated with poorer immune function and greater depression. These data are consistent with epidemiologic evidence linking marital disruption with increased morbidity and mortality.

Stress depresses interferon production by leukocytes concomitant with a decrease in natural killer cell activity.

This study addressed the effects of a commonplace stressful event on interferon production and natural killer (NK) cell activity and numbers. The quantity of interferons (IFN) produced by concanavalin A stimulated leukocytes obtained from 40 medical students during examinations was significantly lower when compared with IFN levels produced by peripheral blood leukocytes (PBLs) taken 6 weeks earlier (baseline). In addition, three different assays measuring NK cells also showed significant decrements during examinations when compared with baseline samples. These assays included lysis of MOLT-4 target cells, percentage of anti-Leu-7+ (NK) cells, and percentage of large granular lymphocytes. Self-report data documented the significantly greater distress associated with examinations in comparison with baseline samples. The data have implications for immunosuppressive disorders and stress-associated illnesses.

Modulation of cellular immunity in medical students.

This study assessed the psychosocial modulation of cellular immunity in 34 medical-student volunteers. The first blood sample was obtained 1 month before examinations, and the second on the day of examinations. There were significant declines in the percentage of helper/inducer T-lymphocytes, in the helper/inducer-suppressor/cytotoxic-cell ratio, and in natural killer-cell activity in the blood samples obtained on the day of examinations. Half of the subjects were randomly assigned to a relaxation group which met between sample points; the frequency of relaxation practice was a significant predictor of the percentages of helper/inducer cells in the examination sample. Three biochemical nutritional assays (albumin, transferrin, and total iron-binding protein) were within normal limits on both samples. Data from the Brief Symptom Inventory showed significantly increased global self-rated distress associated with examinations in the no-intervention group, compared to nonsignificant change in the relaxation group. Clinical and theoretical implications are discussed.

Helping physicians use laboratory tests.

We have described a paradigm for viewing the use of the clinical laboratory in terms of solutions to clinical problems instead of as endless lists of tests. In this regard, we have categorized many of the clinical problems that rely heavily on laboratory testing for their solutions and have suggested ways for readers to develop their own lists for their facilities. We believe that conceptualizing laboratory services in this way can help physicians to use the clinical laboratory in more effective and cost-efficient ways.

Distress and DNA repair in human lymphocytes.

This research assessed differences in DNA repair in lymphocytes from high- and low-distressed individuals. A median split on Minnesota Multiphasic Personality Inventory (MMPI) Scale 2 divided 28 newly admitted nonpsychotic psychiatric inpatients into high- and low-distress subgroups. The high-distress subgroup had significantly poorer DNA repair in lymphocytes exposed to X-irradiation than low-distress subjects. We also found that lymphocytes obtained from this psychiatric sample had significantly poorer DNA repair than lymphocytes from nonpsychiatric control subjects when compared 5 hr after X-irradiation. A high level of distress therefore appears to be associated with significant dysfunctional differences at the molecular level which may have important implications for health. These data provide evidence for a direct pathway through which distress could influence the incidence of cancer.

Stress-related impairments in cellular immunity.

The percentages of total T-lymphocytes (OKT-3+), helper T-cells (OKT-4+), and suppressor T-cells (OKT-8+) were significantly lower in blood samples obtained from 40 medical students during examinations, compared to baseline values obtained 6 weeks earlier. In addition, the response of T-lymphocytes to stimulation by phytohemagglutinin and concanavilin A was also significantly lower during examinations, compared to baseline. Self-report data documented significantly greater distress associated with examinations. The data have implications for immunosuppressive disorders and stress-related illnesses.

Stress, loneliness, and changes in herpesvirus latency.

This study used a prospective design to examine the influence of examination stress and loneliness on herpesvirus latency as measured by changes in antibody levels to three herpesviruses, Epstein-Barr virus (EBV), Herpes simplex type I (HSV-1), and cytomegalovirus (CMV). Three blood samples were obtained from 49 first-year medical students, with the first sample drawn 1 month before final examinations, the second on the first day of final examinations, and the third during the first week after their return from summer vacation. A median split on the UCLA Loneliness Scale divided subjects into high- and low-scoring loneliness groups. There were significant changes in the antibody titers to all three herpesviruses across the sample points, with the lowest levels found in the third (low stress) sample. High-loneliness subjects had significantly higher EBV antibody titers than low-loneliness subjects. These data suggest that stress-related immunosuppression can significantly modulate herpesvirus latency.

Expert systems as aids for interpretive reporting.

Interpretive reporting is an established part of the function of many clinical laboratories. Of the three types of information included in these reports, expert system technology is being demonstrated as useful in producing interpretive comments. The ability of expert systems to explain their reasoning and to be easily updated make them superior to prior attempts to computerize this type of interpretation using traditional computer languages. In the future, the broader application of these systems in realistic clinical environments should be expected given recent commercial success in embedding such programs in laboratory instruments.