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Biomedical subjects

M J Helms

Publications and source records attributed to M J Helms.

43 records · Page 3Linked to original sources

Alzheimer's disease: genetic aspects and associated clinical disorders.

Genetic aspects and associated clinical disorders were studied in a consecutive series of 68 men and women in whom Alzheimer's disease appeared at or before age 70. Secondary cases of dementia were found in 17 (25%) of the families, affecting 22 of the probands' siblings and parents. The cumulative incidence of Alzheimer's disease in these relatives was approximately 14% at age 75. An increased frequency of Down's syndrome was observed among relatives of the probands: a rate of 3.6 per 1,000, as compared with an expected rate of 1.3 per 1,000. A history of thyroid disease was established in 9 (19.6%) of the 46 female probands, a frequency greater than that reported in the general population. There was no excess of hematological malignancies among the blood relatives, and parental age at the time of birth of the probands did not differ from the norm. The results of this study indicate that early-onset Alzheimer's disease is associated with a genetic factor manifested in a substantial familial aggregation of dementia, a probable excess of Down's syndrome in the probands' relatives, and a possible association with thyroid dysfunction in women with this form of dementia.

Aged↗

Risk of stroke in asymptomatic persons with cervical arterial bruits: a population study in Evans County, Georgia.

A survey of the rural community in Evans County, Georgia, revealed cervical arterial bruits in 72 (4.4 per cent) of 1620 persons 45 years of age of older without previous stroke, transient ischemic attacks, or overt ischemic heart disease. The prevalence of such asymptomatic bruits increased with age and was greater in women and persons with hypertension. We estimated the risk of stroke associated with cervical bruits during a six-year follow-up period, taking age and blood pressure into account. The presence of asymptomatic bruits was associated with a significantly higher risk of stroke in men but not in women, with odds ratios of 7.5 and 1.6, respectively. Despite the high risk of stroke among men with bruits, the correlation between the location of the bruits and the type of subsequent stroke was poor. Moreover, cervical bruits in men were a risk factor for death from ischemic heart disease. We suggest that asymptomatic cervical bruits are an indication of systemic vascular disease and do not themselves justify invasive diagnostic procedures or surgical correction of underlying extracranial arterial lesions.

Age Factors↗

Logistic model estimation of death attributable to risk factors for cardiovascular disease in Evans County, Georgia.

Linear logistic analysis of the relationship of cardiovascular disease risk factors to an overall measure of health effect, ten-year mortality, revealed significant associations of death with systolic blood pressure, age, sex, diabetes mellitus, smoking, cholesterol, obesity (Quetelet index), race and social index. Attributable risk and population attributable risk estimates were derived from the model by changing actual variable values to target values. The results confirmed systolic hypertension and smoking as major public health problems and diabetes mellitus as a powerful risk factor for death. The small detrimental effect of cholesterol on probability of death limits the potential for an overall beneficial effect of preventive intervention. In fact, drug intervention in two reported trials of cholesterol reduction had negative overall effects. Demonstration of the association of a characteristic with a specific disease state does not alone justify attempts to eliminate the high risk state from a population. An overall detrimental health effect must be documented by suitable studies before trials of preventive intervention are undertaken or recommendations made to the public.

Adult↗

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.

Adult↗

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.

Age of Onset↗

Depressive symptoms and survival of patients with coronary artery disease.

OBJECTIVE: Multiple studies have shown that high levels of depressive symptoms increase the mortality risk of patients with established coronary disease. This investigation divided depressive symptoms into groups to assess their relative effectiveness in predicting survival. METHODS: Questionnaires about the presence of depressive symptoms were administered to 1250 patients with significant coronary disease while they were hospitalized for diagnostic coronary angiography. Follow-up for mortality due to cardiac disease was conducted annually for up to 19.4 years. Factor analysis was used to divide items on the Zung Self-Rating Depression Scale into four groups: Well-Being, Negative Affect, Somatic, and Appetite. In addition, responses to a single item regarding feelings of hopelessness were available for 920 patients. RESULTS: Well-Being and Somatic symptoms significantly predicted survival (p < or = .01). Negative Affect items were also related to survival (p = .0001) and interacted with age. A 2-SD difference in the Negative Affect term was associated with a relative risk of 1.29 for patients >50 years old and 1.70 for younger ones. Only Negative Affect remained significant in a model with the other symptom groups. Hopelessness also predicted survival with a relative risk of 1.5. Both the Hopelessness and Negative Affect items remained as independent predictors in the same model. All models controlled for severity of disease and treatment. With one exception (income and Hopelessness), results were essentially unchanged by additional controls for age, gender, and income. CONCLUSIONS: Depressive symptoms differentially predicted survival, with depressive affect and hopelessness being particularly important. These effects were independent of disease severity and somatic symptoms and may be especially important in younger patients.

Coronary Disease↗

Central nervous system serotonin function and cardiovascular responses to stress.

OBJECTIVE: The objective of this study was to evaluate the impact of indices of central nervous system (CNS) serotonin function on cardiovascular reactivity to mental stress. METHODS: Lumbar puncture was performed on 54 healthy volunteers to obtain cerebrospinal fluid (CSF) for determination of 5-hydroxyindoleacetic acid (5HIAA) levels. Genotypes were determined with respect to a functional polymorphism of the serotonin transporter gene promoter region (5HTTLPR). Subjects then underwent mental stress testing. RESULTS: Persons with one or two long (l) 5HTTLPR alleles had CSF levels of the major serotonin metabolite, 5HIAA, that were 50% higher than those of persons with the s/s 5HTTLPR genotype. Persons with one or two l alleles or higher CSF 5HIAA levels also exhibited greater blood pressure and heart rate responses to a mental stress protocol. CONCLUSIONS: These findings suggest the 5HTTLPR polymorphism affects CNS serotonin function, and they are consistent with the general hypothesis that CNS serotonin function is involved in the regulation of potentially health-damaging biobehavioral characteristics. In particular, the l allele could contribute, through its association with increased cardiovascular reactivity to stress, to increased risk of cardiovascular disease.

Adult↗