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Biomedical subjects

L W Reinish

Publications and source records attributed to L W Reinish.

9 recordsLinked to original sources

Underlying sleep pathology may cause chronic high fatigue in shift-workers.

About 20-25% of the population in primary healthcare settings complains of chronic fatigue but this symptom has been under-emphasized compared with sleepiness in clinical practice. Shift-workers are particularly vulnerable because of various fatigue-related personal and public morbidity and mortality. The goal of this cross-sectional study was to explore if fatigue severity could be used as an independent predictive tool to identify underlying sleep pathology. The 21 most-fatigued (study group) and 23 least-fatigued (control) miners were selected on the basis of the Fatigue Severity Scale (FSS), which was administered to 195 subjects in an underground mine in Timmins, a town in northern Ontario. The two groups were matched for age, gender, and body mass index (BMI). Mean FSS score for the most-fatigued subjects was 4.9 +/- 0.5 and the least-fatigued was 2.2 +/- 0.5 (P < 0.0001). The subjects from each group were studied polysomnographically to identify sleep disorders. The polysomnographic data in 15 of 21 (71.4%) of the most-fatigued subjects displayed significant sleep pathology compared with only three of 23 (13.0%) in the least-fatigued subjects. Based on Fisher's exact test, the difference between the two groups was highly significant (P < 0.0001). Also, in the total subject pool (n = 195), the correlation between subjective fatigue and sleepiness was not very strong (Pearson's r = 0.45), suggesting that these two symptoms can be independent phenomena. It is concluded that chronic high fatigue can be an independent manifestation of underlying sleep pathology, which warrants independent subjective and objective assessment.

Adult↗

REM changes in narcolepsy with selegiline.

The purpose of this study was to establish the effects of selegiline HCl on sleep parameters in narcolepsy and to contrast these effects with the effects of methylphenidate. Eleven subjects with narcolepsy were studied drug-free and while receiving selegiline (15-30 mg/day) by polysomnography. The methylphenidate-treated group consisted of 11 age-matched subjects with narcolepsy. On overnight polysomnography, compared to pretreatment values, selegiline treatment resulted in a significant increase in rapid eye movement (REM) latency (138.1 +/- 62.8 vs. 48.7 +/- 42.3 minutes, p < 0.05) and sleep stage changes per hour. The increase in REM latency in subjects treated with methylphenidate was marginally significant (116.9 +/- 78.3 vs. 54.3 +/- 23.7 minutes, p = 0.054). Maintenance of wakefulness testing during treatment revealed the methylphenidate-treated group to be significantly more alert than the selegiline-treated group (18.4 +/- 1.9 vs. 9.4 +/- 4.8 minutes, p < 0.001); a retrospective survey of subjects treated with selegiline found that a majority reported clinical improvement with selegiline treatment. These results suggest that selegiline should be considered for further investigation as a treatment for narcolepsy.

Adult↗

Involuntary hospitalization and police referrals to a psychiatric emergency department.

This study compares the demographic and clinical characteristics of police referrals with referrals from other sources to the psychiatric emergency department of a university hospital and the demographic and clinical characteristics of police referrals who were involuntary hospitalized with police referrals who were discharged from the emergency department (ED). In our study, 182 cases were seen in the psychiatric ED over the one-month period; 32 (17.6%) were police referrals. Police referrals were not more frequently hospitalized than referrals from other sources. Police referrals were, however, more likely to have been violent towards others preceding admission (59.4% versus 20.0%; chi 2 = 20.8; df = 1; p < .01) and to be intoxicated on presentation (31.3% versus 10.7%; chi 2 = 91; df = 1; p < .01). Police referrals also were significantly more likely to be violent in the psychiatric ED than referrals from other sources (37.5% versus 3.4%, chi 2 = 36.5, df = 1, p < .01) and to be restrained or secluded (34.4% versus 4.0%; chi 2 = 28.8; df = 1; p < .01). Involuntarily hospitalized police referrals were significantly more likely to be suffering from a major psychiatric disorder than police referrals not hospitalized (83.3% versus 11.8%; chi 2 = 14.7; df = 1; p < .01). They also were significantly more likely to have been violent towards other ED (66.7% versus 23.5%; Fisher test, p < .05) and to have been restrained or secluded in the ED (58.3% versus 23.5%; Fisher test, p < .05) than police referrals who were not admitted.

Adolescent↗

The binding of phosphatidylglycerol liposomes to rat platelets is mediated by complement.

Previous work has shown that intravenous administration of phosphatidylglycercol (PG) containing liposomes to rats results in a rapid transient decline in platelet count (1). Here the interactions of PG liposomes with rat platelets in vitro have been examined with the aim of characterizing factors associated with the decline. It is shown that PG liposomes induce formation of rat (but not human) platelet-liposome microaggregates in vitro. The PG liposome dependent thrombocytopenia observed in vivo can therefore be attributed to sequestration of PG liposome-platelet aggregates. Further, the aggregation of platelets with PG liposomes, which can be monitored as a reduction in platelet count using a coulter counter, is shown to be mediated by a serum complement factor, likely C3b. This is indicated by a requirement of plasma for the in vitro reduction in platelet count induced by PG liposomes, and the inhibition of this effect by heat treatment of plasma, by incubation of plasma with purified cobra venom factor, or by removal of C3 from plasma.

Animals↗

The accumulation of drugs within large unilamellar vesicles exhibiting a proton gradient: a survey.

We have shown previously that transmembrane proton gradients can be used to efficiently accumulate biogenic amines [M.B. Bally et al. (1988) Chem. Phys. Lipids 47, 97-107] and doxorubicin [L.D. Mayer, M.B. Bally and P.R. Cullis (1986) Biochim. Biophys. Acta 857, 123-126] to high concentrations within liposomes. To determine the generality of this loading procedure, representative drugs from a variety of different classes (antineoplastics, local anaesthetics, antihistamines, etc.) were examined as to their ability to redistribute in response to a proton gradient. While the majority of drugs examined, all of which are weak bases, were accumulated by large unilamellar vesicles exhibiting a pH gradient (interior acid) the extent of uptake varied considerably between different pharmaceuticals. These differences are discussed in the context of various factors which will likely influence drug accumulation including its membrane/water partition coefficient and its solubility in the intravesicular medium.

Anesthetics, Local↗

Platelet distribution in rabbits following infusion of liposomes.

This investigation determined the organ distribution of liposomes containing egg phosphatidylcholine and cholesterol with egg phosphatidylglycerol (PG liposomes) or without (PC liposomes) and the effect of each liposome on platelet distribution in rabbits. Eight minutes after 51chromium-labelled platelets were given intravenously, either saline (n = 7), iodinated PG liposomes (n = 5) or iodinated PC liposomes (n = 5) were infused. Two minutes later the organ distribution of 51Cr-platelets and 125I-liposomes were compared. The PG liposomes produced a 41 +/- 5% reduction in circulating platelet counts while PC liposomes did not. The PG liposomes decreased circulating 51Cr-platelets by a factor of 2 and increased platelet recoveries in the liver and lungs. The increased platelet recovery in the liver was associated with a greater PG liposome recovery. When animals receiving PG liposomes were studied over 60 minutes, both the labelled and unlabelled platelet counts returned to control values by 30 minutes and the 51Cr-platelet distribution between organs was similar to control values. These data indicate that platelets and PG liposomes initially sequester together and that this platelet-liposome interaction is specific for PG liposomes. However, the platelet sequestration is transient and by 60 minutes the platelets were released and circulating.

Animals↗

Interactions of liposomes and platelets.

Rats were injected intravenously with liposomes of various compositions and sizes and blood platelet count measured. It was found that negatively-charged liposomal systems produced a transient reduction in platelet count in the first 5 minutes after injection which recovered by 60 minutes post-injection. This effect was most striking for multilamellar vesicles (MLV's) containing phosphatidylglycerol (PG). Dose levels of 25 mg/kg of MLV's containing 10 mole% PG caused the platelet count to drop from a control value of 1,086 +/- 21 X 10(9)/l to 193 +/- 14 X 10(9)/l by 2 minutes post-injection, an 82% decline. This thrombocytopenic effect was observed to diminish as vesicle size or vesicle dose was decreased. Positively-charged liposomes produced a less pronounced transient reduction in platelet count while neutral liposomes caused only a mild, transient platelet decline. This transient thrombocytopenic effect was not blocked by common anticoagulants and fibrinolytic agents but was prevented by liposomal pretreatment. Radiolabeled platelet studies revealed that transient sequestration of platelets occurs in the liver and spleen 2 minutes after PG:EPC:CHOL MLV injection with a normalization of platelet distribution by 60 minutes post-injection. In vitro studies, using an automated blood counter, suggest a transient association of liposomes and platelets occurring following injection. Liposomally-induced transient thrombocytopenia suggests a role for platelets in the biodistribution of liposomes.

Animals↗

Aortic stiffness in the DOCA-hypertensive pig.

Pulsatile changes in aortic diameter and pressure were monitored in order to obtain an index of aortic stiffness in the conscious pig during the development of mineralocorticoid hypertension. The aortic stiffness index increased but to a much lesser extent than it did in response to a similar pressure elevation produced by phenylephrine infusion. This observation suggests that chronic exposure to an elevated pulsatile pressure reduces the stiffness index at the elevated pressure.

Animals↗

Separation of antihypertensive from ganglioplegic effects of felodipine in the cat.

The effects of felodipine on sympathetic ganglionic transmission and on the effector responses of two muscle models were studied. In anesthetized cats we established what injected dose and plasma levels of this selectively vasodilating dihydropyridine were necessary for the neural and for the primary hypotensive effects on arterial blood pressure in vivo. Felodipine in cats reduced mean arterial pressure at a dose of 0.010 mumol/kg i.v., corresponding to a plasma concentration of 10 nmol/L. A 15-25-fold higher dose, or plasma concentration, was required to produce a significant reduction in the amplitude of the sympathetic postganglionic action potential (PAP). The latencies of the PAPs remained constant. Felodipine in vitro did not attenuate the neurogenic response of the nictitating membrane. However, the spontaneous activity, as well as the neurogenic response of the portal vein, was inhibited by felodipine in nanomolar concentrations. Felodipine at the highest dose caused a small but significant attenuation of the postganglionic nictitating membrane response in vivo. This reduction was of insufficient magnitude to account alone for the diminution of the response to preganglionic stimulation. We conclude that felodipine in low concentrations reduces blood pressure by a direct relaxation of vascular smooth muscle, while, in addition, at high concentrations a partial ganglionic blockade may be induced.

Action Potentials↗