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Biomedical subjects

S J Lewis

Publications and source records attributed to S J Lewis.

At least 199 records · Page 11Linked to original sources

Angiotensin receptors and the vagal system.

Angiotensin II (Ang II) is known to attenuate the vagal component of the baroreflex at both central and peripheral cardiac sites. Ang II receptor binding sites occur in both the nucleus of the solitary tract (NTS), where they are associated with vagal afferent terminals, and in the dorsal motor nucleus of vagus. In this study we have examined the distribution of Ang II binding sites in the cell bodies of vagal afferents in the nodose ganglion, and investigated whether these receptors are transported in the vagus nerve. Dense Ang II receptor binding was observed over neuronal cell bodies in the nodose ganglion and, in streaks, in the vagus nerve. Vagal ligation distal to the nodose ganglion resulted in a marked accumulation of receptor binding sites, proximal to the ligature, with a moderate increase on the distal side. These results demonstrate that Ang II receptor binding sites occur in the nodose ganglion and are transported centrally in the vagus to be located on presynaptic terminals in the NTS and also peripherally where they may occur on terminals of the vagus.

Animals↗

A study of zinc status of elderly institutionalized patients.

In a study of zinc status in the elderly, the mean serum and leucocyte zinc concentrations were found to be significantly lower in continuing-care patients compared with elderly people living in the community. The mean daily dietary intakes of zinc, protein and fibre did not differ between the two groups. Serum zinc levels were found to correlate with serum albumin levels. No significant relationship was found between the mean serum or leucocyte zinc concentrations of patients and either their mental status or the presence of skin pressure damage, leg ulcers or unhealed wounds.

Aged↗

Relationship between the dose-response effects of diazepam and clobazam on electroencephalographic parameters and on kindled amygdaloid seizure activity in rats.

1. The possibility that the anticonvulsant activity of the benzodiazepines, diazepam and clobazam, is related to changes in EEG parameters, particularly beta activity, was investigated in amygdaloid kindled rats. 2. The effects of diazepam (1, 2, 4, 8 and 16 mumols/kg), administered intraperitoneally (i.p.), clobazam (1, 2, 4, 8, 16 and 32 mumols/kg, i.p.) or vehicle (dimethyl sulfoxide) on the cortical EEG of amygdaloid kindled rats were quantitated for 15 min using computerized period amplitude analysis. Immediately afterwards, the amygdala was stimulated and the after-discharge duration (AD) and the seizures stage (SS) were determined. 3. The equivalent percentage time (EPT) of the diazepam-treated group was decreased in the theta band (4-8 Hz) and increased in the alpha (8-12 Hz) and first six beta (12-36 Hz) bands. The mean peak amplitude (MPA) was increased in the alpha (8-12 Hz) and all seven beta bands (12-40 Hz). Clobazam increased the EPT and MPA in the alpha (8-12 Hz) and all seven beta (12-40 Hz) bands. The MPA was also increased by clobazam in the theta (4-8 Hz) band. 4. Diazepam reduced both the AD and SS of the kindled seizures at doses of 4, 8 and 16 mumols/kg, whereas clobazam was anticonvulsant at doses of 16 and 32 mumols/kg. The reduction in both AD and SS correlated with increases in the EPT and MPA in the first beta (12-16 Hz) band in the diazepam-treated group and in the first four beta (12-28 Hz) bands in the clobazam-treated group.

Amygdala↗

Involvement of hypothalamic adrenaline in the clonidine withdrawal syndrome in normotensive and spontaneously hypertensive rats.

1. The concentrations of adrenaline and other catecholamines (noradrenaline and its major metabolite DHPG, dopamine and its major metabolite DOPAC) were measured in the hypothalamus and medulla oblongata of normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) which had received a continuous subcutaneous infusion of clonidine (10 micrograms/kg per h) for 10 days, and also in WKY and SHR rats which were killed 15-18 h after the cessation of the 10-day infusion. 2. The concentrations of adrenaline in the hypothalamus and medulla oblongata/pons of the clonidine treated WKY and SHR rats were not different from their respective controls. However, the adrenaline concentrations in the hypothalamus (but not the medulla oblongata) were significantly decreased in the post-infusion WKY and SHR. 3. These results suggest that hypothalamic adrenergic mechanisms may have a common involvement in the post-clonidine infusion syndromes displayed by the WKY and SHR strains.

3,4-Dihydroxyphenylacetic Acid↗

Altered levels of neuropeptides in the medulla and spinal cord of spontaneously hypertensive rats.

1. Spontaneously hypertensive rats (SHR) are useful for investigating the possible pathophysiological and neurochemical basis of human essential hypertension. 2. The accepted pathogenic mechanism of hypertension in SHR is an increased central sympathetic drive which results in an increased peripheral resistance. 3. The neurochemical basis of the increased sympathetic drive is unknown. The observation that there are reduced levels of neuropeptides (vasoactive intestinal peptide, neuropeptide Y, cholecystokinin octapeptide, neurotensin and calcitonin gene related peptide) in the spinal cord in SHR rats compared with age and gender matched Wistar-Kyoto normotensive rats could provide a basis for understanding the mechanism of hypertension in SHR.

Animals↗

Differences in the development of tolerance to two anticonvulsant benzodiazepines in the amygdaloid kindled rat.

The effects of chronic treatment with two benzodiazepines were studied on kindled amygdaloid seizures in rats. Clobazam (4 mg kg-1), clonazepam (0.3 mg kg-1) or vehicle (1 mL kg-1) was administered, by intraperitoneal injection, to fully kindled rats twice daily for nineteen days. Each rat was electrically stimulated 30 min after the morning dose on alternate days of treatment. Tolerance developed rapidly to the anticonvulsant effects of clobazam after only three days of treatment, following which only a small residual protection was maintained. Tolerance to clonazepam developed gradually over the course of the experiment, although this effect was relatively minor.

Amygdala↗

Developing effective invasive cardiology services. Guideline report.

Diseases of the heart are the leading cause of death and the major reason for days stayed in the hospital and discharges from the hospital. Nearly 1 million Americans died last year from cardiac disease, and over 60 million suffer from some form of cardiac disease. Conservatively stated, 300,000 cardiac surgeries and 600,000 cardiac catheterizations are performed annually, and the number is rising. Therefore, heart disease is understandably big business for hospitals and physicians. The organization of cardiac delivery systems is changing dramatically, primarily as the result of advancements made in the nonsurgical treatment of cardiac disease. The balance of power is shifting from cardiac surgery to cardiology, resulting in political and economic consequences for hospitals. Cardiac diagnosis is also undergoing a transformation, as less invasive procedures increase in sophistication. As hospitals consider their options in this market and observe physicians, medical groups, and alternative delivery systems providing competing services, the strategic alternatives become confusing and decidedly difficult. This report is written as a guide to assist hospitals in understanding the technological forces underlying the changing market and the effect these changes will have on the ownership, organization, and structure of delivery systems and, most specifically, on the delivery of cardiovascular services. Because of the tremendous interest in invasive cardiology services and the significance of the financial, organizational, and quality commitment involved in the delivery of invasive cardiology services, this guideline report addresses primarily those services. Noninvasive technologies also are addressed because of their importance to a cardiology program, the magnitude of the technological changes taking place, and their potential impact on the diagnosis and treatment of cardiac disease. The report begins with a discussion of the general planning issues that provide the foundation for the development of an effective cardiology program and details the methodologies and practices necessary to implement the planning process. Included are market assessment and financial planning models, which contain sample reports and provide conceptual and factual starting points for market-specific planning in such areas as demographic and market research, equipment costs, staffing considerations, and pricing alternatives. In addition to strategic, financial, and market planning issues, the report addresses the clinical factors involved in the operation of a cardiology department.(ABSTRACT TRUNCATED AT 400 WORDS)

Cardiac Catheterization↗

Medial prefrontal cortical lesions and baroreceptor heart rate reflex sensitivity in the spontaneously hypertensive rat.

Previous investigations have shown that an excitotoxic lesion of the medial prefrontal cortex (MPFC) in normotensive Sprague-Dawley rats results in a reduction in the sensitivity of the baroreceptor heart rate reflex. The aim of this study was to examine the importance of the MPFC in regulation of the heart rate reflex in conscious, unrestrained spontaneously hypertensive rats (SHR). The MPFC was lesioned by bilateral microinfusions of the excitotoxin N-methyl-D-aspartic acid (NMDA). Baroreceptor heart rate reflex testing was performed by measuring reflex heart rate changes in response to blood pressure alterations induced by nitroprusside and phenylephrine with subsequent computerized sigmoidal curve-fitting of the data. Lesion of the MPFC did not significantly alter resting, systolic and diastolic blood pressure, heart rate or baro-reflex parameters (gain, thresholds, range or plateaus). These observations suggest that the putative descending facilitatory influence from the MPFC to brainstem areas, involved in baroreceptor reflex regulation observed in normotensive rats, may be defective in SHR.

Animals↗

Medial prefrontal cortical lesions modulate baroreflex sensitivity in the rat.

Previous neuroanatomical studies in rats have demonstrated that the medial prefrontal cortex sends projections to the nucleus of the solitary tract which also receives the bulk of baroreceptor information from primary afferents within the IXth and Xth cranial nerves. The present study examines the influence of the prefrontal cortex on baroreceptor heart rate reflex in conscious rats. Baroreceptor reflex activity was examined in rats with bilateral excitotoxin (N-methyl-D-aspartate)-induced lesions of the medial prefrontal cortex and in control rats (artificial cerebrospinal fluid). Seventeen to eighteen days after lesioning, reflex heart rate responses were recorded following intravenous bolus doses of the pressor agent phenylephrine and the depressor agent sodium nitroprusside. Baroreceptor reflex parameters i.e., maximum and average baroreceptor reflex gain (or sensitivity): minimum and maximum heart rate plateaus; heart rate range; upper and lower reflex thresholds, were determined by sigmoidal computerized curve-fitting. Lesioning the medial prefrontal cortex did not affect resting mean arterial pressure and heart rate. However, the lesion reduced maximum and average baroreceptor reflex gain and produced a small reduction in lower reflex threshold. The other parameters were unaffected by the lesion. These observations suggest that although the medial prefrontal cortex does not exert a tonic influence on brainstem vasomotor neurons, there may be a descending excitatory projection from this brain region to medullary neurones involved in the baroreceptor reflex arc.

Animals↗

Strain differences in central nervous system neurotensin content between normotensive and spontaneously hypertensive rats.

Regional brain concentrations of neurotensin (NT) were measured in age-matched normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive (SH) rats. The relative distribution of NT was similar in the two strains with the hypothalamus having the highest concentration (55-75 pmol/g) and the cerebellum the lowest (3-6 pmol/g). In comparison to the WKY rats, the SH rats had significantly lower NT levels in the hypothalamus (-17%), medulla oblongata-pons (-18%), pituitary (-52%) and spinal cord (-44%). In view of the putative role of NT as a neurotransmitter and its cardiovascular effects following central and peripheral administration, the reduced levels of this peptide may be of importance in the higher blood pressure of the SH rat.

Animals↗

Microcomputer analysis techniques for evaluation of benzodiazepine effects on rat electrocorticogram.

Quantitative analysis of drug effects on the EEG is usually performed on a minicomputer using an EEG signal that has been recorded on a high frequency FM tape recorder and edited to remove artefact. However, this equipment is expensive and so the present study evaluated a much cheaper system, an 'on-line' microcomputer and 3 programs for data reduction. Using this system to assess diazepam effects on the rat electrocorticogram, it was concluded that period amplitude analysis may be preferable to the Fast Fourier Transform or Hjorth analysis.

Animals↗

The development of tolerance to the anticonvulsant effects of clonazepam, but not sodium valproate, in the amygdaloid kindled rat.

The effects of chronic treatment with clonazepam and sodium valproate were studied on kindled amygdaloid seizures in rats. Fully kindled rats were given an intraperitoneal (i.p.) injection of either vehicle (1.0 ml/kg), clonazepam (0.3 mg/kg) or sodium valproate (200 mg/kg) twice daily for 12 days. Each rat was stimulated through an amygdaloid electrode 30 min after the morning dose. While both drugs initially blocked and kindled seizure (P less than 0.01), the results showed a significant trend (P less than 0.02) in the development of tolerance to the anticonvulsant action of clonazepam but no significant tolerance to the action of valproate.

Amygdala↗

Concentrations of histamine in the hypothalamus of the rat: effect of extraction volume and interpretation of the effects of acutely-administered morphine.

The effect of varying the ratio of extraction volume to tissue weight (EVR) on the apparent concentration of histamine (HA) in the hypothalamus of the rat was examined. Increasing the weight of tissue (by pooling 1, 2 or 3 hypothalami), in a constant extraction volume, resulted in progressive decreases in apparent concentration of histamine in the hypothalamus. These concentrations were 642, 450 and 282 ng/g, respectively. Morphine (10 mg/kg, i.p.) significantly reduced the concentration of histamine in the hypothalamus. Expressed as percentages of the saline-control values (obtained for the extraction volume to tissue weight of 35.7, 57.2 and 118.4 ml/g), treatment with morphine resulted in 24, 17 and 11% reductions in the concentration of histamine in the hypothalamus, respectively. However, expressed in terms of ng/g, the reductions in histamine induced by morphine were 68, 75 and 69 ng/g, respectively. It is concluded that morphine may consistently affect a single pool of histamine. The possibility that de novo histamine is formed in the homogenate during the extraction process is discussed.

Animals↗

The N-methyl-D-aspartate (NMDA) receptor antagonist MK-801, attenuates the Bezold-Jarisch reflex in the anaesthetized rat.

The effects of MK-801, an N-methyl-D-aspartate (NMDA) receptor antagonist, on the Bezold-Jarisch reflex elicited by i.v. doses of 5-hydroxytryptamine (5-HT) was investigated in urethane-anaesthetized rats. Activation of the Bezold-Jarisch reflex with 5-HT (0.5-16 microgram/kg) produced pronounced dose-dependent hypotensive and bradycardic responses which were attenuated by MK-801 (1 mg/kg, i.v.) but not by saline. The data suggests that activation of the Bezold-Jarisch reflex by 5-HT involves a glutamatergic synapse presumably located within the brainstem vagal reflex arc.

Anesthesia↗

Rapid eye movement sleep and the associated cardiovascular changes during and after continuous 10-day infusion of clonidine in normotensive rats: comparison with lofexidine and S3341.

The centrally acting alpha-adrenoceptor agonists clonidine, lofexidine, and S3341 vary in their selectivity for the alpha 2-adrenoceptor subtype (S3341 greater than clonidine greater than lofexidine). The aim of this study was to examine the frequency and duration of rapid eye movement (REM) sleep episodes, and the cardiovascular changes associated with these episodes, during and after the continuous (10-day) infusion of saline (0.9% wt/vol), clonidine (10 micrograms/kg/h), lofexidine (10 micrograms/kg/h), or S3341 (50 or 100 micrograms/kg/h) in unrestrained, chronically instrumented rats. During a typical 24-h period, the saline infusion animals (n = 4) had 46 +/- 3 REM sleep episodes of 2.4 +/- 0.1 min duration. The majority of these episodes were associated with relatively minor phasic and tonic changes in arterial blood pressure and heart rate. During infusion, the three drugs markedly reduced the cardiovascular and behavioural signs of REM sleep. On cessation of the clonidine and lofexidine infusions, rebound increases (i.e., to values greater than controls) in the frequency and duration of REM sleep episodes were observed. These episodes were associated with markedly exaggerated fluctuations in arterial blood pressure and heart rate. The REM sleep rebound and associated cardiovascular responses were greater during the post-lofexidine infusion phase. A relatively minor rebound increase in total REM sleep time was observed after cessation of the 100-micrograms/kg/h, but not the 50-micrograms/kg/h, infusion rate of S3341. The cardiovascular responses during the REM sleep episodes were mildly exaggerated after cessation of the higher infusion rate of S3341.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Microflora associated with the internal surfaces of rubber and stainless steel milk transfer pipeline.

Sterile sections of rubber and stainless steel milk transfer pipeline were inserted sequentially into a milking installation and soiled with fresh raw milk over a period of 5 d. The resultant adherent microbial population was removed and the generic composition of mesophilic and psychotropic types was determined. In all cases Acinetobacter spp. were found to predominate (59.5-75.6%). The generic composition of the raw milk used to soil the milking unit (with inserted pipe section) was determined once during each 5-d soiling period. In general the milk was found to contain a mixed flora in which Gram-positive organisms predominated.

Animals↗