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Biomedical subjects

E B Larson

Publications and source records attributed to E B Larson.

At least 253 records · Page 14Linked to original sources

Intracellular calcium response is reduced in CD4+ lymphocytes in Alzheimer's disease and in older persons with Down's syndrome.

Abnormalities in intracellular free calcium ([Ca2+]i) regulation are likely to play a role in brain aging and have been described in cells from patients with Alzheimer's disease (AD). [Ca2+]i acts as a second messenger in transmembrane signaling and regulates diverse functions in many cell types. Therefore, abnormalities in [Ca2+]i response may have far-ranging effects. Using flow cytometric assay for [Ca2+]i, we examined whether mitogen-induced increases in [Ca2+]i are abnormal in CD4+ T-lymphocytes from patients with familial AD (FAD), other AD, and Down's syndrome (DS) compared to age-matched controls. We observed that the peak [Ca2+]i responses were significantly decreased in CD4+ cells from 6 FAD patients (59% of control), 34 other AD patients (69% of age-matched control), and 6 older persons with DS (> 25 years old, 47% of control), after stimulation with 10 micrograms/ml anti-CD3 monoclonal antibody (mAb). The number of CD3 receptors on T lymphocytes of the AD patients was not decreased. In contrast, lymphocytes from subjects with FAD, other AD and older DS patients had no decrease in response to phytohemagglutinin (30 micrograms/ml). CD3 and related classes of membrane receptors are present on many cells of the central nervous system. Therefore, receptor signaling defects via this receptor in T lymphocytes of AD patients may be relevant to the central nervous system pathology seen in AD and DS.

Adult↗

Relationship between serum alpha 1-antichymotrypsin and Alzheimer's disease.

We obtained serum samples and measured alpha 1-antichymotrypsin (ACT) levels in 36 pairs of consecutive probable Alzheimer's disease (AD) patients and age- and sex-matched, cognitively intact control subjects. Serum ACT was measured by radial immunodiffusion. Unique to this study, we found that ACT levels rose significantly with age within controls (but not within AD cases), thus ACT may be related to the aging process. Consistent with other reports, we found that AD cases had greater serum ACT in 27 of 36 pairs [mean difference = 135.5 (SE = 50.8) mg/l (p < 0.05)]. Severity and duration of AD were not significantly associated with the observed difference. The ACT increase observed in AD is not sufficient to recommend ACT's use as a diagnostic marker for AD. Because adult Down's syndrome (DS) persons are known to have pathologic features of AD, we also measured serum ACT levels in 11 adult, noninstitutionalized, DS persons paired with 11 age- and sex-matched, volunteer control subjects; we found no statistically significant difference. The unexpected age-associated increase in ACT among normal controls could be an indicator of early amyloid plaque formation. Future studies comparing ACT levels in both serum and cerebrospinal fluid should help to clarify the origin of ACT found in amyloid plaques and its value as a diagnostic marker for AD.

Adult↗

Embryonic cocaine exposure and corticosterone: serotonin(2) receptor mediation.

Cocaine activates the mature hypothalamic-pituitary-adrenal (HPA) axis, increasing corticosterone concentrations in animals and humans and serotonin(2) receptors (5-HT(2)) are involved in this effect. Although prenatal cocaine exposure is associated with altered responsiveness of the HPA axis to "stress" and serotonergic compounds postnatally, it is unknown whether cocaine directly activates the embryonic HPA axis or if 5-HT(2) receptors are involved. Domestic chicken eggs with viable embryos were exposed to either the 5-HT(2) receptor agonist dimethoxyiodophenylaminopropane (DOI: 0.4, 0.8, or 1.2 mg/kg egg) or saline on embryonic day 18 (E18). In a second study, the 5-HT(2) antagonist ritanserin (0.3 mg/kg egg, a dose found effective against other effects of DOI or cocaine) or vehicle was administered on E17, prior to treatment on E18 with either saline or cocaine (5 injections of 12 mg/kg egg, equivalent to a total dose of 3.5 mg/egg). Radioimmunoassay was used to measure serum corticosterone from blood samples taken approximately 1-2 h after drug injections. DOI significantly raised corticosterone in a dose-related fashion. Cocaine-induced corticosterone elevations were blocked by pretreatment with ritanserin, whereas ritanserin by itself did not affect corticosterone concentrations. These data indicate that 5-HT(2) receptors are involved in cocaine's effect on the HPA axis during late chicken embryogenesis.

Amphetamines↗

Cost-benefit analysis of a plateletapheresis program.

We determined costs and benefits of a community donor plateletapheresis program (CDPP) designed to provide HLA-matched platelet transfusions for patients who were refractory to random-donor platelets (RDPs). Costs of establishing and maintaining the CDPP were $127,520 for the first year (1982). Benefits were expressed as cost savings attributed to the CDPP. After the program began, the use of RDP in the community was 17,458 units less than projected. Estimates of net cost savings during the first year ranged from $177,570 to $272,253 (1982 dollars; cost-to-benefit ratios were 1:1.39 to 1:2.14.) In a matched cohort study of marrow transplant patients, CDPP platelet transfusions were as effective as those from family donors while total platelet and red cell use was unchanged. In patients with acute leukemia treated with chemotherapy, significant reduction in both platelet and red cell use was seen after institution of CDPP support. We conclude that the CDPP is a cost-effective approach to platelet support.

Acute Disease↗

Case report. Tumoral calcinosis: an unusual complication of the laxative abuse syndrome.

A 47-year-old woman who abused laxatives as a means of weight control is described. Her laxative abuse resulted in an episode of tetany for which she was given long-term calcium and vitamin D therapy. This therapy, along with the ingestion of absorbable phosphate and alkali, and large amounts of milk, led to the development of tumoral calcinosis. The failure to fully appreciate the contribution of laxative abuse in her metabolic imbalance resulted in this complication.

Calcinosis↗

Occupational exposure to electromagnetic fields and Alzheimer disease.

The association between occupational exposure to electromagnetic fields (EMF) and Alzheimer disease (AD) was examined. Subjects were identified from a large health maintenance organization in Seattle, Washington, and matched by age, sex, and proxy type. A complete occupational history was obtained from proxies and controls. Following the interview, two industrial hygienists (IHs) rated exposures to EMF for each job blinded to case-control status. Exposures to EMF were rated as probable intermittent exposure or probable exposure for extended periods to levels above threshold. Conditional logistic regression was used to calculate the risk of AD given EMF exposure stratified by IH. The odds ratios for ever having been exposed to EMF were 0.74 [95% confidence interval (CI) 0.29-1.92] and 0.95 (95% CI 0.27-2.43) for each IH, adjusting for age and education. No dose-response effect was noted. Agreement between the two IHs for ever having been exposed to EMF was good (kappa = 0.57, p < 0.0001). This study was unable to support an association between EMF and AD.

Adult↗

Drug-induced cognitive impairment. Defining the problem and finding solutions.

Drug-induced cognitive impairment is a common cause of delirium and is frequently a confounding factor in dementia. Predisposing conditions for delirium include age, brain disease and addiction to alcohol and/or drugs. The elderly are at particular risk because of multiple diseases, multiple drug use and alterations of drug metabolism associated with age. Sedatives such as benzodiazepines have a particularly high risk of cognitive impairment. Centrally acting sympathetic antihypertensive agents, sedating antipsychotic drugs, opioids, digitalis, anti-Parkinsonian drugs, antidepressants and corticosteroids are also associated with greater risk relative to other classes of medications. Cognitive impairment due to medication may be reduced by recognition of the problem. The risk of drug-induced impairment may be minimised by strategies which optimise overall health, avoidance of unnecessary medications, and selection of medications least likely to cause delirium.

Aged↗

Participation by sedentary elderly persons in an exercise promotion session.

BACKGROUND: Little is known regarding the dynamics of elderly persons' participation in health promotion programs. We studied factors influencing the participation of 337 sedentary elderly persons in an exercise promotion session. All study participants were members of a health maintenance organization. METHODS: Baseline data were obtained on 337 persons age 65 and older who exercised irregularly or not at all. These individuals were then offered a class emphasizing individualized exercise activities for elderly persons. Participation in the exercise program was used as the dependent variable, and the baseline data were analyzed to identify factors associated with participation. RESULTS: There was no difference between participants and nonparticipants for age and sex. Baseline physical activity, as measured by the Paffenbarger index and self-report of physical activity, also did not differentiate participants from nonparticipants, nor did frequency of self-reported medical conditions. Participants were more likely to be nonsmokers, but the two groups did not differ with respect to other preventive health practices. Participants were characterized by more social interactions, as reflected by attendance at at least two meetings per month. Participants also were more likely to report three or more close friends. Perceived quality of life and self-reported health status were not significantly different between the two groups. Participants rated their current health slightly worse than nonparticipants. In a logistic regression model controlling for age and sex, lower current health perceptions, greater number of friends, prior expressed intent to participate in an exercise program, being a nonsmoker, and having received an influenza vaccination in the past year were significantly associated with participation. CONCLUSIONS: Participation in this exercise program may have appealed to persons with higher levels of social interaction. In this population, age, sex, and the number and type of self-reported medical conditions at baseline were not predictive of participation.

Aged↗

Treatment of atopic dermatitis with antihistamines: lessons from a single-patient, randomized clinical trial.

BACKGROUND: Single-patient randomized clinical trials (RCTs) can be utilized to maintain methodologic precision in the analysis of treatment effect in individual patients. We describe the results of a single-patient RCT in a patient with atopic dermatitis and review practical considerations regarding the use of antihistamines. METHODS: Using double-blind, crossover techniques, the patient was randomly allocated to four 2-week treatment periods with the following regimens: chlorpheniramine, 8 mg twice daily; chlorpheniramine, 12 mg twice daily; terfenadine, 120 mg twice daily; and placebo (phase 1). The drug that produced superior results from phase 1 (chlorpheniramine, 8 mg) was subsequently compared with astemizole, 10 mg/d, during phase 2, consisting of four 4-week, double-blind, crossover trial periods with random allocation of study drugs. Daily symptom scores, as well as end of treatment period summary impressions by patient and investigator, were analyzed. RESULTS: In both phases, chlorpheniramine produced the most noticeable positive therapeutic effect on the patient's mild but most disturbing symptoms (pruritus and eye irritation) associated with atopic dermatitis. Drowsiness was reported with chlorpheniramine. Tolerance to this side effect, however, developed quickly. CONCLUSIONS: A single-patient RCT with different antihistamines in a patient with chronic atopic dermatitis was a useful tool in achieving a favorable balance among efficacy, toxicity, and cost of therapy.

Adult↗

Crossing to safety: transforming healthcare organizations for patient safety.

The current healthcare system is not designed to ensure better patient safety. In addition, healthcare is simultaneously becoming increasingly complex and increasingly fragmented. Medical knowledge and technology are expanding at an incredible rate, making it difficult for the healthcare providers to keep pace with advancing knowledge. Patients' needs are changing too: shifting from the diagnosis and treatment of a single, acute problem to the long-term management of multiple, interrelated chronic conditions. Our systems of care are not keeping up with these changes and, consequently, patients are experiencing unnecessary risk. Improving patient safety requires a transformation in how we currently care for patients. Healthcare organizations must adopt a new paradigm of care that holds patient safety as a core value and practice. To achieve this aim, healthcare organizations should build and maintain a culture of patient safety, provide leadership for patient safety that establishes a blame-free environment, proactively survey and monitor for adverse events, continually engineer patient safety into healthcare processes, and provide information and communication technologies to support patient safety.

Hospital Administration↗

Interrelationships of general internal medicine and preventive/community medicine.

Clinical preventive medicine, efforts by clinicians to prevent disease in individual patients, is an important component of preventive medicine as a whole. Yet clinicians, including internists, apparently do not provide many preventive services of established effectiveness. This paper describes one approach to improving the practice of clinical preventive medicine: increased cooperation between general internists--one of the nation's largest groups of primary care physicians--and specialists in preventive/community medicine. The paper summarizes a larger report prepared by two societies representing these disciplines: the Society for Research and Education in Primary Care Internal Medicine and the Association of Teachers of Preventive Medicine. It was found that the two disciplines have many common goals, and much to offer each other, but do not often collaborate. The report concludes with 14 recommendations for improving the practice of clinical preventive medicine, which suggest that such improvement can be achieved in part through strengthening working relationships between general internists and preventive/community medicine specialists.

Internal Medicine↗