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Biomedical subjects

R K Davidson

Publications and source records attributed to R K Davidson.

14 recordsLinked to original sources

Phenelzine produces subsensitivity to nicotine.

1. The authors attempted to detect a possible effect of treatment with phenelzine on a physiological response to nicotine in the rat. 2. Positive findings in an animal model suggest the feasibility of more complicated experiments in animals and the possibility of studies involving human subjects. 3. Treatment of Sprague Dawley rats (n = 10) with phenelzine sulfate (15.0 mg/kg ip) every 48 hours for 14 days was associated with a 73.3% decrease in the hypothermic response to nicotine. 4. Treatment with phenelzine did not enhance the rate of elimination of nicotine. 5. The authors discuss a possible relationship between changes in nicotinic mechanisms and the therapeutic actions of drugs used to treat affective illness.

Animals↗

A nicotinic receptor antagonist enhances the hypothermic response to a muscarinic agonist.

1. Chronic treatment with amitriptyline produces supersensitivity to the hypothermic effects of the muscarinic agonist oxotremorine. 2. Chronic treatment with amitriptyline also produces supersensitivity to the hypothermic effects of nicotine. 3. Oxotremorine and other naturally occurring muscarinic agonists are also nicotinic agonists. 4. Chronic treatment with amitriptyline produces time-dependent and reversible supersensitivity to the hypothermic effects of nicotine. 5. The authors assessed the possibility that the development of supersensitivity to oxotremorine following chronic treatment with amitriptyline is related to an effect of this antidepressant on a nicotinic mechanism. 6. A nicotinic receptor antagonist would blunt (though not necessarily eliminate) enhanced sensitivity to the thermic effects of oxotremorine if the nicotinic effects of the latter are significant. 7. The simultaneous administration of mecamylamine (a peripherally and centrally active nicotinic receptor antagonist) greatly augments (rather than blunts) the hypothermic response to oxotremorine. 8. The data suggest that the oxotremorine may activate a nicotinic mechanism counterbalancing its effect on a muscarinic mechanism. 9. This is consistent with previously published reports that the activation of nicotinic and muscarinic mechanisms can exert opposite effects.

Animals↗

Chronic treatment with amitriptyline produces subsensitivity to the hypothermic effects of yohimbine.

1. Two but not one week of treatment with amitriptyline (AMI) produces subsensitivity to the hypothermic effects of the alpha 2 antagonist yohimbine. 2. Subsensitivity persisted for the three weeks during which it was measured following the discontinuation of AMI. 3. Two weeks of twice daily injections of saline did not alter the thermic response to this agent. 4. The results support other data indicating tricyclic antidepressants (TCAs) subsensitize alpha 2 mediated thermic changes and are consistent with reports that TCAs down-regulate alpha 2 receptors.

Amitriptyline↗

Desipramine subsensitizes nicotinic mechanism involved in regulating core temperature.

Desipramine HCl, 10 mg/kg i.p. twice daily, produced subsensitivity to the hypothermic effects of nicotine, 1 mg/kg, after 1 and 2 weeks of treatment in male Sprague-Dawley rats, Phenelzine sulfate, fluoxetine HCl, and bright artificial light produced the same effect. The capacity of three chemically distinct classes of anti-depressants and bright artificial light (a treatment for seasonal depression) to produce this result suggests that effects on nicotinic mechanisms may be involved in the mechanism of action of these treatments.

Amitriptyline↗

Fluoxetine subsensitizes a nicotinic mechanism involved in the regulation of core temperature.

Fluoxetine HCl, 10 mg/kg ip, twice daily produced subsensitivity to the hypothermic effects of nicotine (base), 1 mg/kg ip, after 1 (p less than 0.02) and 2 (p less than 0.002) weeks of treatment. Phenelzine sulfate, desipramine HCl and bright artificial light produced the same effect. The capacity of three chemically distinct classes of antidepressants and bright artificial light (a treatment for seasonal depression) to produce this result suggests that effects on nicotinic mechanisms may be involved in the mechanism of action of these treatments.

Animals↗

The economics of parasitic diseases: research priorities.

Parasitic diseases are primarily diseases of poverty. At serious risk are individuals, communities and countries least able to afford the costs of treatment or prevention. In turn, economic development projects which aim to increase income levels may lead to negative results because of increased transmission of parasitic diseases often results. In attempting to analyse the economic consequences of parasitic diseases and the economics of their control, economists have usually relied on the tools of cost-benefit analysis, cost-effectiveness analysis and financial analysis. These efforts are briefly reviewed in the paper. The results have been subject to considerable criticism because of conceptual and methodological problems. For example, most studies have not taken into account the epidemiology and natural history of the disease in estimating the associated economic losses, thereby leading to inappropriate conclusions. The UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases through its Social and Economic Research Scientific Working Group (SER-SWG) is promoting research on the economics of parasitic diseases. In an attempt to improve the usefulness and reliability of such studies, conceptual and methodological approaches have been suggested which are reported on here. To improve the research design of these projects, a conceptual framework is proposed which consists of four components: (1) baseline social, cultural and economic conditions influencing disease transmission; (2) resources already invested in the health system and investments in other related sectors such as agriculture, housing, water supply and sanitation; (3) health consequences resulting from (1) and (2); and (4) social and economic consequences resulting from (3). A key concern in relation to the framework is to determine the most useful basis for linking results from studies of one component to another so as to analyse more systematically the impacts of disease on individuals and society. Such studies are inherently interdisciplinary and close collaboration of economists with medical scientists and disease control programme staff is needed to ensure completeness and reliability of input data and results. Results from these studies could be used to inform national decision-makers about the social and economic consequences of the parasitic diseases and their control and, thus, should strengthen support for increased investment to reduce the parasitic disease burden in developing countries.

Communicable Disease Control↗

Potassium evoked catecholamine release from the nucleus tractus solitarius in vitro.

The release of endogenous catecholamines (CA) from rat brain slices containing the nucleus tractus solitarius (NTS) was measured using a sensitive radioenzymatic assay. KCl (35 to 75 mM) induced a dose-related increase in norepinephrine (NE) release. Dopamine (DA) release was maximal with 50 mM KCl. An increase in epinephrine (E) release was only observed with 75 mM CKl. NE and E release was totally calcium-dependent whereas DA release was only partially calcium-dependent. Subsequent administrations of KCl released less CA. The calcium dependency of the KCl induced released of E, NE, and DA suggests a neurotransmitter function in the NTS for these CA. A difference in storage sites and/or mechanisms may be responsible for the observed differences in sensitivity to KCl and to extracellular calcium.

Animals↗

Carotid artery stenosis - hemodynamic significance and clinical course.

Two hundred fifteen patients with a history of either stroke, transient ischemic attack (TIA), or asymptomatic carotid bruit underwent noninvasive carotid artery testing using oculopneumoplethysmography. Of patients with hemodynamically significant stenosis, 51 (40.8%) underwent endarterectomy, and 74 (59.2%) were treated nonoperatively. The incidence of stroke in the nonoperated group was 12/74 (16.2%) compared with only 1/51 (1.9%) in the operated group. Similarly, recurrent TIA occurred in 29/74 (39.2%) of the nonoperated group vs 9/51 (17.6%) of the operated. In nonhemodynamically significant carotid stenosis, the risk of cerebrovascular death and stroke was exceedingly low: 2/90 (2.2%). Patients with hemodynamically significant stenosis treated nonoperatively have a greater risk of cerebrovascular death, stroke, and TIA than patients treated with carotid endarterectomy.

Arterial Occlusive Diseases↗

Effect of prophylactic antibiotics in acute nonperforated appendicitis: a prospective, randomized, double-blind clinical study.

A prospective, randomized, double-blind clinical study was performed to determined the efficacy of short-term (24 hr) perioperative antibiotics in preventing septic complications after emergency appendectomy for nonperforated appendicitis. The patients were stratified into three clinical arms: Group I (placebo, n = 45), Group II (cefamandole, n = 46) and Group III (cefamandole plus carbenicillin, n = 45). The three groups of patients were similar in regard to age, sex, duration of operation and pathologic classification of the appendix. The overall incidence of infection in the study was 5.1%. The infection rates in Groups II (2.2%) and III (0%) were significantly lower than Group I (placebo) (13.3%), (p less than 0.05). No difference was observed between cefamandole alone and cefamandole plus carbenicillin. Average postoperative hospital days per patient for each group was: Group I - 3.8 days; Group II - 2.9 days; Group III - 3.1 days. Cost analysis of hospitalization including cost of prophylactic antibiotics revealed a $247.99 per patient saving for Group II versus Group I and $95.53 for Group III versus Group I. Systemic prophylactic antibiotics can successfully reduce septic complications after appendectomy for nonperforated appendicitis, and a single drug (cefamandole) directed at the facultative pathogens is as effective as double drug therapy, which includes specific anaerobic coverage.

Acute Disease↗

Selective management of extracranial carotid arterial aneurysms.

Aneurysms of the extracranial carotid arteries are rare vascular lesions that produce a high incidence of unfavorable neurologic sequelae. In the past 24 years, 19 patients at UCLA Hospital were treated for angiographically demonstrable extracranial carotid arterial aneurysms. These cases were reviewed to determine the natural history of these lesions as influenced by various modes of therapy in order to develop a logical treatment plan for these difficult patients. Because of the varied location of these lesions, proper treatment requires a diversity of techniques. Gratifying results can be achieved when a carefully selected operative approach is undertaken.

Adult↗