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Biomedical subjects

R F Barnes

Publications and source records attributed to R F Barnes.

At least 19 recordsLinked to original sources

Sympathetic nervous system activity in major depression. Basal and desipramine-induced alterations in plasma norepinephrine kinetics.

BACKGROUND: To determine whether elevations of plasma norepinephrine (NE) in major depression represent increased sympathetic nervous system (SNS) activity and to assess the effects of desipramine hydrochloride on sympathetic function. METHODS: SNS activity was assessed in depressed patients and controls by an isotope-dilution, plasma NE kinetic technique using mathematical modeling and compartmental analysis. This approach provided estimates of the rate of NE appearance into an extravascular compartment, which is the site of endogenous NE release from SNS nerves, the corresponding rate of NE appearance into plasma, and the rate of NE clearance from plasma. RESULTS: Norepinephrine appearance into the extravascular and vascular compartments was significantly elevated in 17 depressed patients compared with that in 36 controls. The rate of NE clearance from plasma was similar in both groups. This is compatible with increased SNS activity in major depression. Desipramine, given for 2 days, significantly reduced the concentration of NE in plasma of patients and controls by markedly suppressing the rates of extravascular and vascular NE appearance, compatible with a short-term reduction in SNS activity. Desipramine prolonged the rate of NE clearance from plasma, consistent with a blockade of NE re-uptake into SNS nerve terminals. The initial suppression of SNS activity by desipramine was reversed by long-term (28 days) treatment of patients, with extravascular and vascular NE appearance rates returning to approximately basal levels. An associated rise in plasma NE concentrations compared with the baseline was attributable to a progressive reduction in plasma NE clearance. CONCLUSION: Sympathetic nervous system activity is elevated in major depression and is suppressed by short-term desipramine administration. The demonstration of SNS reactivation occurring with prolonged desipramine treatment is compatible with the theory that long-term treatment desensitizes CNS alpha 2-adrenergic receptors and emphasizes the value of examining the temporal course of responses to pharmacological challenges of neuroendocrine systems. Previously reported elevations of plasma NE during prolonged administration of tricyclic antidepressants are probably the result of a reduction in plasma NE clearance, not an increase in SNS activity.

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Impaired sympathetic nervous system response to cognitive effort in early Alzheimer's disease.

Sympathetic nervous system responses to a cognitive challenge and a physiologic stimulus (upright posture) were compared in 10 patients with early Alzheimer's Disease and a group of healthy older adults. Plasma catecholamine and cardiovascular responses to upright posture were similar in the two groups. However, sympathetic activation during mental effort was impaired in the patient group; this difference did not appear to be attributable to motivational factors. Alzheimer's Disease is associated with a defect in sympathetic nervous system function that is specifically linked to cognitive effort and appears early in the course of the disease.

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Medical illness in chronic psychiatric outpatients.

A careful physical and laboratory evaluation of 144 chronic psychiatric outpatients revealed medical illnesses in 26%. Chart review indicated that 13% of the patients had illnesses that were previously undetected and that 13% of the patients received some form of new treatment because of the evaluation. The majority of the illnesses did not appear to have directly caused or exacerbated psychiatric symptoms. Because medical illnesses were relatively common in this population, psychiatrists caring for chronic psychiatric outpatients often need to assume some of the health care referral and coordinating functions typically associated with a primary care physician.

Adult↗

Tricyclic antidepressants and supine, standing, and exercise plasma norepinephrine levels.

Fourteen depressed patients were treated for 1 to 8 wk (4.1 +/- 0.6, mean +/- SEM) with imipramine, doxepin, or amitriptyline to study the effects of tricyclic antidepressants (TCAs) on sympathetic nervous system (SNS) function. Eight had chronic but medically stable cardiac disease and six were medically healthy. Supine plasma norepinephrine (NE) and epinephrine (EPI) levels, mean arterial blood pressure (MAP), and heart rate were measured at rest, after standing, and during graded, supine maximal bicycle exercise. Eight nondepressed patients with cardiac disease were studied without drug intervention as controls. There were no baseline differences in any of these measures among the medically healthy depressed subjects, the depressed cardiac patients, and the eight nondepressed patients matched for cardiac disease. After TCAs, NE was increased by 51 +/- 6% of basal values and heart rate rose, but EPI and MAP were unchanged. The supine to 10-min standing increment in NE increased from 309 +/- 51 pg/ml at baseline to 406 +/- 55 pg/ml during TCA treatment. These findings are compatible with an increase in SNS outflow after TCAs.

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Cardiovascular effects of tricyclic antidepressants in depressed patients with chronic heart disease.

Twenty-four depressed patients with heart disease were treated for four weeks in a double-blind trial of imipramine, doxepin, or placebo to assess the effects of tricyclic antidepressants on ventricular function and rhythm. The tricyclic antidepressants had no effect on left ventricular ejection fraction at rest or during maximal exercise, as measured by radionuclide ventriculograms obtained before and after treatment. Premature ventricular contractions were reduced by imipramine but were not consistently changed by doxepin or placebo. Treatment with imipramine and doxepin, but not placebo, was associated with significant improvement (P less than 0.001) in standard ratings of depression. Our findings underscore the need for a reappraisal of the cardiovascular risks of tricyclic antidepressants and suggest that in the absence of severe impairment of myocardial performance, depressed patients with preexisting heart disease can be effectively treated with these agents without an adverse effect on ventricular rhythm or hemodynamic function.

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Screening for depression in hospitalized geriatric medical patients.

As part of an effort to improve the detection of depression in geriatric hospitalized medical patients, the validity of two self-rating depression scales, the Zung Self-rating Depression Scale (SDS) and the Popoff Index of Depression (ID), was evaluated. These two scales were completed by 42 medical inpatients whose mean age was 68 years. A psychiatrist who was "blind" to scale results interviewed each patient and diagnosed the presence or absence of depression according to the Diagnostic and Statistical Manual-III (DSM-III) criteria for Major Depressive Episode. On both the SDS and the ID, there was significant agreement between the scale results and the interview diagnosis. Compared with the interview diagnosis, the SDS had a sensitivity of 58 per cent and a specificity of 87 per cent, and it correctly identified 74 per cent of the patients as being either depressed or nondepressed. The ID had a sensitivity of 88 per cent and a specificity of 52 per cent, and it correctly identified 66 per cent of the patients. Although performance on both scales is reduced compared with that of younger depressed patients, these self-rating scales appear to be useful aids for the detection of depression in geriatric medical patients.

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Screening for depression in geriatric medical patients.

Depression, a common and treatable psychiatric disorder in later life, is often overlooked in geriatric medical patients. The authors evaluated the validity of two self-rating depression scales, the Zung Self-Rating Depression Scale and the Popoff Index of Depression, for 55 elderly patients. They compared these ratings with the diagnosis assigned by a psychiatrist who was blind to scale results and who interviewed these patients using DSM-III criteria. The two scales correctly classified 80% and 69% of the subjects, respectively. The authors identify six items from the two scales that may serve as a simple screening instrument for the detection of depression in geriatric medical patients.

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The effects of age on the plasma catecholamine response to mental stress in man.

To determine if sympathetic nervous system activity is heightened during psychological stress in older adults, plasma norepinephrine (NE), epinephrine (EPI), heart rate, and blood pressure were measured in 10 healthy old (mean age, 68.5 yr) men and 10 healthy young (mean age, 26.6 yr) men during a 12-min mental stress test. Basal NE was higher in old than in young men (400 +/- 33 vs. 286 +/- 32 pg/ml: p less than 0.01). Consistent significant increases in plasma NE occurred only in the elderly and mean increases (delta) in NE during testing were significantly greater (P less than 0.01) in the old than in the young men. Compared to basal levels, plasma EPI increased by 2 min in both young (delta EPI, 50 +/- 20 pg/ml; P less than 0.02) and old subjects (delta EPI, 41 +/- 11; P less than 0.01) and remained significantly increased throughout the test. There was no difference in either basal or delta EPI between young and old men. Heart rate and blood pressure were significantly increased throughout testing for both age groups. Although the delta blood pressure during testing tended to be greater in the old men, this difference was not statistically significant. Conversely, the delta heart rate was greater in the young subjects (P less than 0.005). Since EPI increases were similar in old and young men, mental stress-related adrenomedullary activation does not appear to change with age. However, the increased plasma NE response in the elderly suggests that they have heightened activity of postganglionic sympathetic neurons during psychological stress.

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DSM-III criteria and the clinical diagnosis of dementia: a nursing home study.

Examinations were given to 64 elderly nursing home patients who met DSM III criteria for dementia to determine if a specific diagnosis for their dementing disorder could be established through clinical evaluation. Pre-established diagnostic criteria were followed in diagnosing the cause of a patient's dementia. The diagnostic criteria for primary degenerative dementia, multi-infarct dementia, or alcoholic dementia were the same as those in the DSM-III. All but four of the patients evaluated could be given a specific, criteria based diagnosis for the cause of their dementia. The two most common diagnoses were primary degenerative dementia (56%) and multi-infarct dementia (27%). Existing chart diagnoses for these 64 patients did not appear to be adequate as 39% had only a nonspecific diagnosis such as "organic brain syndrome," 30% had no diagnosis of any kind related to an organic mental disorder, and 8% had an inaccurate arteriosclerotic cerebro-vascular diagnosis. These results suggest that demented nursing home patients have discrete clinical syndromes which can be assigned a specific diagnosis and that the current clinical diagnosis of these disorders can be greatly improved.

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Problems of families caring for Alzheimer patients: use of a support group.

An eight-week support group program was conducted for 15 members of the families of Alzheimer patients still living at home. It became clear that caring for an Alzheimer patient at home created tremendous practical, psychologic and social problems for family members. Frequently discussed problems included lack of support and information from physicians, poor understanding of the disease, depression, a trapped feeling, anger and fear about the patient's behavioral problems, isolation, and the caretaker's loss of self-identity. Group participation was especially beneficial for spouses who functioned as primary care providers. It increased their understanding of the disease, made them feel more supported and less isolated, and helped them resolve some of the feelings created by the illness. It also helped spouses to become more aware of their own needs and to regain some self-identity in relation to the patient. Such family support programs offer a way to strengthen the emotional well-being and treatment skills of the care-providing family and are an important aid to treatment in Alzheimer's disease.

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