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Biomedical subjects

S J Lewis

Publications and source records attributed to S J Lewis.

At least 163 records · Page 9Linked to original sources

Home assessments in geriatrics revisited: an audit of a routine home visiting service.

Routine home visiting is a luxury not afforded to other medical specialties. The practice of routine home assessment visiting in geriatric medicine was evaluated in a prospective study of 110 consecutive referrals to determine whether; the response to general practitioners referrals could be predicted from the information given at the time of referral and; to identify where home visiting identified additional information of value in directing services more appropriately. Requests for admission were accurately predicted in 86-96% of cases by the visiting and a control doctor respectively. Additional information of value in directing services and patient management was gained from the home visit in 30% of admissions, 58% of day hospital cases and 80% of outpatients. It is possible to predict the outcome of home visits although implementation of such predictions without direct communication with general practitioners would result in a small number of unnecessary admissions and referrals to day hospital services.

Aged↗

Altered cardiovascular responses to glutamate and acetylcholine microinjected into the nucleus tractus solitarii of the SHR.

L-glutamate (GLU) or acetylcholine (ACh) injected into the nucleus tractus solitarii (NTS) of rat elicits a decrease in arterial pressure (AP) and heart rate (HR) similar to that seen with activation of the baroreflex. Both compounds may play a role in the mediation of the baroreflex at the level of NTS. The baroreflex may be disturbed in the spontaneously hypertensive rat (SHR). Thus we sought to determine if the dose-related responses to microinjection (50 nl) of the two putative transmitters into NTS may be altered in SHR vs Wistar Kyoto (WKY) controls. Both GLU and ACh produced significant dose-related decreases in AP and HR in SHR and WKY. The dose-related changes in AP elicited by GLU were shifted significantly to the right in SHR compared to WKY. Responses of AP were only different after intermediate doses of ACh. The dose-related HR responses to GLU were the same in SHR and WKY. However, the HR response to ACh was significantly reduced in the SHR. These data suggest that cardiovascular regulation in the NTS through GLU and ACh mechanisms may be disturbed in the SHR.

Acetylcholine↗

Cardiovascular responses produced by the systemic injection of kainic acid in conscious WKY and SH rats.

This study examined the cardiovascular effects of systemic injections of the excitatory amino acid analogue (EAA) kainic acid (KA) in conscious normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive (SH) rats. The injection of KA (100-1000 micrograms/kg, i.v.) produced dose-dependent but transient pressor and tachycardic responses followed by a prolonged period of bradycardia in both strains. Higher doses of KA also produced a secondary prolonged depressor response in WKY but not SH rats. Pharmacological studies demonstrated that the pressor and tachycardic responses are due mainly to increased sympathetic drive to the vasculature and heart. The KA-induced depressor response in the WKY is due principally to cardiovagal activation. After ganglionic blockade, KA produced a prolonged pressor response which was due to the release of vasopressin. These results indicate that the systemic administration of EAAs may produce their cardiovascular effects by activation of the autonomic nervous and endocrine systems and that the absence of the KA-induced hypotension in the SH rats may be related to an abnormality of cardiovagal function in this strain.

Animals↗

Reduced nociceptive effects of intravenous serotonin (5-HT) in the spontaneously hypertensive rat.

This study compared the cutaneous (baseline tail-flick (TF) latencies) and visceral nociceptive responses (5-HT-induced inhibition of the TF reflex and pseudaffective responses) in lightly pentobarbital-anesthetized 16 week old Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). SHR were significantly less sensitive to the nociceptive effect of i.v. 5-HT compared to WKY rats. That is, SHR had a greater quantal ED50 for inhibition of the TF reflex than WKY rats (50.0 and 15.1 micrograms/kg, respectively). SHR also showed the presence of distinct pseudaffective responses (flattening of the ears, closure of the eyes to slits and contraction of the facial musculature) at much greater doses than in WKY rats, thereby paralleling the same changes in sensitivity observed the 5-HT-induced inhibition of the TF reflex. 5-HT-induced similar cardiovascular responses in WKY and SHR except that the SHR showed a significantly greater pressor response compared to WKY rats. These results demonstrate that the SHR show a marked reduction in sensitivity to the nociceptive, but not the cardiovascular, responses to i.v. 5-HT.

Animals↗

A comparison of four measures to diagnose DSM-III-R borderline personality disorder in outpatients.

After three decades of clinical controversy and research, a clinical consensus has formed that borderline personality disorder (BPD) exists as a unique entity which can be defined by DSM-III-R diagnostic criteria. The purpose of this study was to evaluate the relative abilities of four different approaches to the identification of borderlines and to differentiate a DSM-III-R BPD group from a control group of other diagnoses. The approaches were the Kernberg's Structural Interview, the Diagnostic Interview for Borderline Personality Disorders (DIB), the Borderline Syndrome Index (BSI), and the Million Clinical Multiaxial Inventory (MCMI). Sixty outpatient volunteers (27 men and 33 women) from a community mental health center served as subjects. The volunteers included 30 BPDs and 30 other diagnoses, including 11 non-BPD personality disorders. Point biserial correlations indicated that the best method for identifying DSM-III-R BPD was the DIB, and the second best was the Kernberg Structural Interview, although all four identified DSM-III-R BPDs at better than chance levels. Multiple regression results showed that the DIB accounted for 61.5% of the BPD variance, while the Kernberg approach added 4.9% more unique variance prediction. MCMI dimensions and personal history characteristics were used to identify differentiators of BPD from all other diagnoses and from other personality disorders.

Adolescent↗

Is there a role for an endothelium-derived relaxing factor in nociception?

Many of the circulating algesic agents released in response to ischemia produce a profound vasodilatation possibly through the release of an endothelium-derived relaxing factor (EDRF) as well as pain. We report here that intravenously administered S-nitrosocysteine, a putative EDRF, and not the nitric oxide liberating compound sodium nitroprusside produces significant alterations in nociceptive behavior that are abolished by bilateral vagotomy. These results are consistent with a role for EDRF in peripheral nociceptive mechanisms.

Analysis of Variance↗

Vagal afferent-mediated inhibition of a nociceptive reflex by intravenous serotonin in the rat. I. Characterization.

The effect of intravenous (i.v.) serotonin (5-HT) on nociception and blood pressure was examined in male Sprague-Dawley rats. Intravenous 5-HT produced a dose-dependent (6-192 micrograms/kg, i.v.) inhibition of the nociceptive tail-flick (TF) reflex in lightly pentobarbital-anesthetized (ED50 = 40 micrograms/kg) and conscious rats (ED50 = 44 micrograms/kg). In the lightly pentobarbital-anesthetized rat, the blood pressure response to i.v. 5-HT was typically a triphasic response with a marked Bezold-Jarisch reflex-induced decrease in pressure (associated with a brief period of apnea) followed by a pressor phase and a subsequent delayed hypotension. In the conscious rat, the response was typically biphasic with the late hypotensive phase absent. A variety of anatomical and pharmacological manipulations were performed to characterize the 5-HT-induced inhibition of the TF reflex and associated changes in blood pressure. Prevention of 5-HT-induced reflex apnea by artificial ventilation did not affect inhibition of the TF reflex produced by 5-HT. Pharmacological manipulations were performed to mimic, as closely as possible, the acute increases and decreases in blood pressure associated with i.v. 5-HT. Nitroprusside (8 micrograms/kg, i.v.) produced a decrease in blood pressure of similar magnitude and rate as that associated with the Bezold-Jarisch reflex-induced decrease in pressure produced by 72 micrograms/kg 5-HT, but did not change TF latency from baseline. Similarly, acute increases in pressure produced by phenylephrine (8 micrograms/kg, i.v.), intended to mimic the secondary pressor effect of 5-HT, did not change TF latency. The short-acting ganglion blocker trimethaphan (5 mg/kg, i.v.) closely mimicked the late hypotensive phase produced by 5-HT, but again resulted in no change in TF latency. Pretreatment with the ganglion blocker chlorisondamine (2.5 mg/kg) abolished all depressor responses to 72 micrograms/kg 5-HT, but did not significantly affect the TF reflex. These results indicate that acute changes in blood pressure and respiration associated with i.v. 5-HT do not contribute to inhibition of the TF reflex. This conclusion was confirmed in experiments in which bilateral vagotomy abolished approximately 70% of the 5-HT-induced inhibition of the TF reflex (and all depressor responses), and resulted in a significantly greater pressor response. Finally, low thoracic spinal cord transection (T9-10) abolished the inhibition of the TF reflex produced by i.v. 5-HT. Therefore, 5-HT stimulates vagal afferents and inhibits the TF reflex by activating descending inhibitory systems from the brainstem.(ABSTRACT TRUNCATED AT 400 WORDS)

Afferent Pathways↗

Factor structure of the MCMI among personality disordered outpatients and in other populations.

This study examined the factor structure of the Millon Clinical Multiaxial Inventory (MCMI) for a sample (N = 60), which consisted largely of personality disordered outpatients. Results are integrated with previous studies to identify the underlying MCMI dimensions across differing psychiatric populations. Three principal axis Varimax rotated factors emerged from the current study: affectively charged general maladjustment; impulsive acting-out style; and psychotically tinged isolation. Comparison with results of previous studies that involved four diverse samples indicated a large amount of stability for scales that load on the first factor. Factor two shows much less consistency across the five studies, but frequent reappearance of the drug abuse and other acting-out scales suggests a general dimension that reflects acting-out substance abuse. Across studies the third factor shows even more inconsistency, although there is some evidence for a social detachment pattern.

Adolescent↗

Excitotoxin-induced degeneration of rat vagal afferent neurons.

The inferior vagal or nodose ganglion contains the perikarya of vagal afferent neurons that function as cardiopulmonary and abdominal visceral receptors as well as aortic arch baroreceptors. In this study we have sought to utilize the axon-sparing properties of the excitotoxins kainic acid, N-methyl-D-aspartic acid and alpha-amino-3-hydroxy-4-isoxazolepropionic acid to destroy the perikarya of these sensory neurons and thus selectively de-afferent the vagus in the rat. Kainic acid (0.5 nmol/microliters, 2 X 2 microliters) was applied topically to both nodose ganglia and the rats were allowed to recover for 7-8 days. Baroreceptor heart rate reflex activity was assessed in these conscious rats. Baroreceptor heart rate reflex gain was reduced (-51%) in kainic acid-treated rats, as was the maximal reflex bradycardia induced by the pressor agent, phenylephrine. Kainic acid treatment did not alter resting mean arterial pressure or heart rate. Vagal efferent neurons were spared by kainic acid treatment since bradycardic responses to electrical stimulation of the peripheral end of a cut vagus were not impaired. Histological studies showed marked destruction of perikarya within the nodose ganglia of kainic acid-treated rats: inflammatory and degenerative changes were evident at 2 days, and at 10 days there was considerable loss of neuronal cell bodies, but sparing of axons. Topical application to the nodose ganglion of alpha-methyl-DL-aspartic acid (6.8 nmol/microliters, 2 X 2 microliters), a non-excitotoxic dicarboxylic acid, failed to alter baroreflex sensitivity or produce perikaryal degeneration in nodose ganglia.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Expression of HIV-1 gp120 and human soluble CD4 by recombinant baculoviruses and their interaction in vitro.

The soluble domains of the envelope glycoprotein of HIV-1 (gp120) and human CD4 (sCD4) have been individually expressed in insect cells using recombinant baculoviruses. Each product is secreted from infected cells and accumulates in the surrounding media to levels of 1-2 mg/liter of 2 x 10(9) cells. Both molecules have full biological activity, and conditioned media from infected cells have been used to establish a simple assay for gp120-sCD4 interaction that is highly specific and amenable to mass screening. The crystallization of sCD4 purified from this source is reported.

Animals↗

The application of test data in the selection and use of gloves against chemicals.

Within recent years there have been a number of papers on the testing of protective clothing materials for degradation, penetration and permeation by chemicals. However, little guidance has been provided concerning the practical application of such data in the selection and use of gloves. A scheme is proposed for the selection of appropriate gloves and for deciding whether they should be reused. This takes into account the toxic properties of the chemical involved, the type of activity being undertaken and the degree of protection afforded by a particular material as indicated by data obtained from standard tests.

Chemical Industry↗

Regional brain concentrations of calcitonin gene-related peptide in spontaneously hypertensive and normotensive Wistar-Kyoto rats.

The regional brain and spinal cord concentrations of calcitonin gene-related peptide (CGRP) were measured in age-matched (22-23-week-old) spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats. The highest concentration of CGRP in the WKY rats was in the spinal cord (172 +/- 9 pmol/g), followed by the medulla oblongata/pons (88 +/- 5 pmol/g). The relative order of distribution in the remaining regions was: hypothalamus (12.6 +/- 0.8 pmol/g) = striatum greater than thalamus greater than midbrain = hippocampus greater than cortex (2.1 +/- 0.3 pmol/g). The concentration of CGRP in the cerebellum was at the level of the assay's sensitivity (0.5 pmol/g). The relative order of distribution in the SHR strain was essentially the same. However, in comparison with the WKY rats, the SHR had significantly lower levels of CGRP in the hippocampus (-47%), striatum (-49%) and medulla oblongata/pons (-24%), and in the spinal cord (-24%). In younger age-matched (16-17-week-old) rats, the spinal cord and medulla oblongata/pons concentrations of CGRP were also lower in SHR than in WKY rats. CGRP is a putative neurotransmitter which, when administered centrally or peripherally, has potent cardiovascular effects. The reduced levels of this peptide may be an important factor in the cardiovascular and/or behavioural abnormalities of the SHR strain.

Animals↗

Role of central mineralocorticoid binding sites in development of hypertension.

The possibility that central mineralocorticoid binding sites are involved in the development of mineralocorticoid hypertension was examined using chronic blockade of these sites with a specific mineralocorticoid receptor antagonist RU 28318 administered by intracerebroventricular (icv) infusion. The antagonist significantly attenuated the development of deoxycorticosterone acetate (DOCA)-salt hypertension, but the development of one-kidney, one-clip renal hypertension was not affected. This antihypertensive action was attributable to a central action, since intraperitoneal infusion of the same dose of mineralocorticoid antagonist did not alter the peak development of DOCA-salt hypertension. The icv infusion of RU 28318 did not change either the increase of fluid intake induced by DOCA-salt treatment or the pressor reactivity to centrally or peripherally injected arginine vasopressin and angiotensin II and peripherally administered phenylephrine. The antihypertensive action of icv infusion of the mineralocorticoid antagonist was associated with a reduction of neurogenic vasomotor tone and a restoration of impaired arterial baroreflexes. We conclude that functional integrity of central mineralocorticoid binding sites is required for the full development of DOCA-salt hypertension.

Animals↗

Nociceptive afferent vagal input is enhanced after transection of the aortic depressor nerve.

To test the hypothesis that baroreceptor reflexes are involved in the reduced nociceptive responses associated with hypertension, the effects of acute intravenous doses of serotonin (0.75-144 micrograms/kg) on inhibition of the tail-flick reflex, blood pressure, and heart rate were examined in lightly pentobarbital-anesthetized Sprague-Dawley, Wistar-Kyoto, and spontaneously hypertensive rats before and after bilateral transection of the aortic depressor nerve. Before transection, the ED50s for inhibition of the tail-flick reflex in the three strains of rats were 14, 13, and 44 micrograms/kg, respectively. After bilateral transection of the aortic depressor nerve, all three strains displayed a significant increase in sensitivity toward the serotonin-induced inhibition of the tail-flick reflex (ED50s of 7, 7, and 6 micrograms/kg, respectively). There were no changes in the cardiovascular responses to serotonin after transection of the aortic depressor nerve in Wistar-Kyoto or spontaneously hypertensive rats. In Sprague-Dawley rats, however, the cardio-pulmonary cardiovascular afferent-mediated responses were enhanced. In Sprague-Dawley rats, the nociceptive sensitivity to serotonin was unaltered when administered during either the peak increase or decrease in pressure produced by intravenous phenylephrine or nitroprusside, respectively. These results suggest that 1) afferent fibers within the aortic depressor nerve provide strong tonic inhibitory influences on the noxious information conveyed by the vagus in response to intravenous serotonin and 2) these fibers appear to produce their effects by mechanisms that are unrelated to baroreceptor function.

Afferent Pathways↗

Excitotoxin-induced lesions of the central but not basolateral nucleus of the amygdala modulate the baroreceptor heart rate reflex in conscious rats.

The present study has examined the influence of the central nucleus of the amygdala (Ce) and the basolateral nucleus of the amygdala (BL) on the baroreceptor heart rate (HR) reflex in conscious, unrestrained rats. Baroreceptor HR reflex activity was examined in rats with bilateral excitotoxin (N-methyl-D-aspartate; 40 nmol/side)-induced lesions of the Ce or the BL and in control rats (artificial cerebrospinal fluid). After lesioning, the reflex HR responses were recorded following intravenous bolus doses of the pressor agent phenylephrine and the depressor agent sodium nitroprusside. Baroreceptor reflex parameters were determined by sigmoidal computerized curve-fitting. Lesions of either the Ce or the BL failed to affect resting mean arterial pressure (MAP) or HR. However, the Ce lesion reduced the maximum and average gain (sensitivity) of the baroreceptor reflex, and diminished the range of the reflex by altering the minimum, but not the maximum HR plateau. The upper and lower reflex thresholds and the MAP value corresponding to the midpoint of the HR range were not affected. Bilateral lesions of the BL failed to modify any baroreceptor reflex parameters. These results suggest that despite previous evidence for the involvement of the BL in cardiovascular regulation this nucleus does not exert a tonic influence on vasomotor neurons nor does it influence the baroreceptor HR reflex. In contrast, neurons projecting from the Ce appear to provide excitatory input to medullary neurons involved in baroreceptor reflex are regulation.

Amygdala↗

Evolution of late potential activity in the first six weeks after acute myocardial infarction.

The evolution of surface ventricular late potential activity was studied in 50 patients during the 6 weeks after first acute myocardial infarction (AMI). In 15 of 47 patients (32%) late potential activity appeared within 6 hours of the onset of major symptoms. Its prevalence overall remained approximately 30% at each recording time but with marked individual variability in appearance. Late potential activity was associated with late ventricular arrhythmias (greater than 24 hours after AMI) but not with early ventricular arrhythmias (less than 24 hours after AMI). Late ventricular arrhythmias or sudden death occurred only in the 6 patients with late potential activity (p less than 0.05). Early ventricular fibrillation (15 patients) occurred equally in the patients with and without late potential activity. Thus, late potential activity occurs at some stage in the first 6 weeks after AMI in 50% of patients, but its timing is variable. It is a sensitive but not specific predictor of late ventricular arrhythmias and sudden death, but not of early ventricular fibrillation.

Adult↗

A demonstration of the advantages of immunostaining in the quantification of amyloid plaque deposits.

Extracellular amyloid deposits are a feature of both Alzheimer type dementia and the 'normal' aging process. Quantification of amyloid plaque deposits may well be useful in distinguishing between the senescent changes associated with 'normal' aging and the pathological processes underlying dementia. To determine the most reliable and reproducible method for visualisation of the amyloid we have compared conventional silver staining techniques with beta-amyloid immunocytochemistry on a large sample of post-mortem brain tissue from both demented (n = 15, age range 60-87) and non-demented (n = 65, age range 14-99) patients. The degree of amyloid deposition was rated on a four point scale and ratings for the two techniques were significantly correlated (P less than 0.01). However, the immunocytochemical approach has a number of distinct advantages for quantification. The antibody to beta-amyloid is highly specific and does not stain neurofibrillary tangles or background features, it is considerably more sensitive than silver staining in highlighting diffuse amyloid deposits and, perhaps most importantly, it produces high contrast staining which allows easier image digitisation and subsequent computer image analysis.

Adolescent↗