Search PubMed⌕ Search

Biomedical subjects

S J Lewis

Publications and source records attributed to S J Lewis.

At least 145 records · Page 8Linked to original sources
PubMed1992

Vagal afferent-mediated inhibition of a nociceptive reflex by i.v. serotonin in the rat. II. Role of 5-HT receptor subtypes.

In the rat, intravenous (i.v.) serotonin (5-HT) is a noxious stimulus which produces distinct vagal afferent-mediated pseudoaffective responses, a passive avoidance behavior, a vagal afferent-mediated inhibition of the nociceptive tail-flick (TF) reflex and a complex triad of cardiovascular responses. In the present study, we have used a variety of 5-HT receptor antagonists to characterize the receptor subtype(s) in the rat that mediate (1) inhibition of the TF reflex and (2) the cardiovascular responses produced by i.v. 5-HT. 5-HT produced a dose-dependent (3-72 micrograms/kg, i.v.) inhibition of the TF reflex (ED50 = 15.3 +/- 0.7 micrograms/kg). Following administration of the 5-HT2 receptor-selective antagonists ketanserin (50-250 micrograms/kg, i.v.) or xylamidine (10-100 micrograms/kg, i.v.), or the 5-HT3 receptor-selective antagonists ICS 205-930 (50-250 micrograms/kg, i.v.) or MDL 72222 (25-250 micrograms/kg, i.v.), there appeared to be a parallel shift of the 5-HT dose-response curve to the right. Following co-administration of xylamidine (50 micrograms/kg, i.v.) with ICS 205-930 (100 micrograms/kg, i.v.), the 5-HT-induced inhibition of the TF reflex was completely abolished at all doses of 5-HT tested (3-288 micrograms/kg, i.v.). In contrast, administration of the centrally acting 5-HT2 receptor-selective antagonist LY 53857 (10-100 micrograms/kg, i.v.) or the non-specific receptor antagonist methysergide (25-500 micrograms/kg, i.v.) resulted in a dose-dependent, but not parallel shift of the 5-HT dose-response curve to the right. The maximal doses of LY 53857 and methysergide tested (250 micrograms/kg and 500 micrograms/kg, respectively) completely abolished the effects of 5-HT (3-288 micrograms/kg, i.v.). Administration of the alpha 1-adrenoceptor antagonist prazosin (25-100 micrograms/kg, i.v.) failed to alter the 5-HT dose-response curve, indicating that the effects of ketanserin were due to blockage of 5-HT2 receptors rather than alpha 1 receptors. Administration of each of the antagonists also produced marked, but selective effects on components of the complex cardiovascular response to i.v. 5-HT. Each of the 5-HT3 receptor selective antagonists (ICS 205-930 or MDL 72222) produced a dose-dependent attenuation of the Bezold-Jarisch reflex-mediated hypotension and bradycardia, and each of the 5-HT2 receptor selective antagonists (xylamidine, ketanserin or LY 53857) produced a dose-dependent attenuation of the pressor response. The non-specific 5-HT receptor antagonist methysergide produced a dose-dependent attenuation of the 5-HT-induced pressor response.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1992

The accuracy of self and informant ratings of physical functional capacity in the elderly.

To compare the accuracy of self-ratings with informant-ratings of physical functional capacity in the elderly, 150 elderly patients attending a geriatric day hospital (GDH) and their formal and informal community carers were administered a questionnaire about their ability to perform activities of daily living (ADL). Direct observation of the patients' performance by therapists at the GDH was used as a standard, after the reliability and validity of this approach had been evaluated. Self-ratings were shown to be more accurate and less biased than informant-ratings, both for individual ADL and overall functional capacity. The accuracy of all ratings tended to be greater for less complex or physically demanding ADL, and informants tended to consistently underestimate functional capacity. The concurrent validity of the adapted Barthel Index in a self-report format was also demonstrated. Wherever possible, information concerning the physical functional capacity of an elderly subject should in the first instance be sought from the subject himself, as the quality of such information may be superior to that of his carers.

Activities of Daily Living↗
PubMed1992

Arterial pressure lability and renal sympathetic nerve activity are dissociated in SAD rats.

The purpose of this study was to determine whether the sympathetic nervous system drives the high variability of arterial pressure (AP) observed after sinoaortic denervation (SAD) in rats. One or fourteen days after SAD, rats were instrumented chronically to record mean AP (MAP), heart rate (HR), and renal sympathetic nerve activity (RSNA) in the conscious unrestrained state. Acute SAD increased MAP, HR, RSNA, and variability of MAP and decreased variability of both HR and RSNA. In rats with chronic SAD, variability of MAP remained high, whereas MAP, HR, RSNA, and variability of HR and RSNA returned to normal levels. Correlation analysis showed that, in sham-operated rats, AP and RSNA were negatively correlated in 90% of cases. In contrast, rats with both acute and chronic SAD exhibited only 30% negative and 25% positive correlations. These results indicate that 1) low AP variability in intact rats results from baroreflex-mediated inversely related fluctuations in RSNA and HR and 2) high variability of AP after acute and chronic SAD is correlated infrequently with RSNA. Because lability is reduced by interventions that block the sympathetic nervous system, we conclude that lability of AP associated with SAD appears to be mediated largely by a permissive role of sympathetic activity.

Animals↗
PubMed1992

Chronic lesion of rostral ventrolateral medulla in spontaneously hypertensive rats.

We studied the effects of chronic selective neuronal lesion of rostral ventrolateral medulla on mean arterial pressure, heart rate, and neurogenic tone in conscious, unrestrained spontaneously hypertensive rats. The lesions were placed via bilateral microinjections of 30 nmol/200 nl N-methyl-D-aspartic acid. The restimulation of this area with N-methyl-D-aspartic acid 15 days postlesion failed to produce a pressor response. One day postlesion, the resting mean arterial pressure was significantly decreased in lesioned rats when compared with sham rats (100 +/- 7 versus 173 +/- 4 mm Hg, p less than 0.05). Fifteen days later, the lesioned group still showed values significantly lower than the sham group (150 +/- 6 versus 167 +/- 5 mm Hg, p less than 0.05). No significant heart rate differences were observed between the sham and lesioned groups. The ganglionic blocker trimethaphan (5 mg/kg i.v.) caused similar reductions in mean arterial pressure in both lesioned and sham groups. The trimethaphan-induced hypotension was accompanied by a significant bradycardia in lesioned rats (-32 +/- 13 beats per minute) but a tachycardia in sham rats (+33 +/- 12 beats per minute) 1 day postlesion. Therefore, rostral ventrolateral medulla neurons appear to play a significant role in maintaining hypertension in conscious spontaneously hypertensive rats. Spinal or suprabulbar structures could be responsible for the gradual recovery of the hypertension in the lesioned rats.

Animals↗
PubMed1992

The delivery of interim discharge summaries to general practitioners by the elderly.

Two hundred and four patients discharged from an acute geriatric unit were given an interim discharge summary for delivery to their General Practitioner (GP). All but three summaries were received by the practices. Information regarding mode and timing of receipt was available in 191 patients. The summaries were received in a median of 1.0 day in both those living alone and those living with family; 75% of summaries had been received within two days of discharge and 93% within four days. General practitioners collected the summaries from patients' homes in a high proportion of both groups. Interim discharge summaries should be given to elderly patients for delivery to their GPs: this is both reliable and rapid, and clearly more cost-effective than any other form of delivery.

Aged↗
PubMed1991

The peripheral nociceptive actions of intravenously administered 5-HT in the rat requires dual activation of both 5-HT2 and 5-HT3 receptor subtypes.

In 16-week-old Sprague-Dawley rats lightly anesthetized with pentobarbital, 5-HT (3-96 micrograms/kg, i.v.; n = 6) produced distinct pseudaffective responses and a dose-dependent (slope = 17.2 +/- 6.8 s/log10 dose) inhibition of the tail-flick (TF) reflex (ED50 = 32.6 +/- 9.2 micrograms/kg). In the same rats, a 1:1 combination of alpha-methyl 5-HT (a 5-HT2, receptor selective agonist) and 2-methyl 5-HT (a 5-HT3 receptor selective agonist) (3-192 micrograms/kg, i.v.), produced the same profile of pseudaffective responses and also resulted in a dose-dependent (slope = 34.0 +/- 7.0 s/log10 dose) inhibition of the TF reflex (ED50 = 88.4 +/- 20.5 micrograms/kg). In contrast, administration of alpha-methyl 5-HT (3-192 micrograms/kg, i.v.) or 2-methyl 5-HT (3-192 micrograms/kg, i.v.) alone did not produce any pseudaffective responses or any change in TF latency from baseline. In conscious 16-week-old male Sprague-Dawley rats, administration of 5-HT (48 micrograms/kg, i.v.; n = 5), or a 1:1 combination of alpha-methyl 5-HT and 2-methyl 5-HT (total dose = 120 micrograms/kg, i.v.; n = 5), resulted in a passive avoidance behavior assessed in a step-down paradigm (slopes = 139.7 +/- 58.2 and 154.9 +/- 63.9 s/trial, respectively), and the same profile of distinct pseudaffective responses exhibited by the lightly pentobarbital-anesthetized rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Neonatal capsaicin treatment abolishes the nociceptive responses to intravenous 5-HT in the rat.

The intravenous (i.v.) administration of serotonin (5-HT) to lightly pentobarbital-anesthetized rats is known to produce a triad of reflex cardiovascular responses, distinct afferent-mediated pseudaffective reactions, and a vagally mediated inhibition of the nociceptive tail-flick (TF) reflex consistent with 5-HT acting as a noxious stimulus. In the present experiments we examined the involvement of capsaicin-sensitive afferents in mediating these responses. Lightly pentobarbital-anesthetized 16-week-old male Sprague-Dawley rats which had been treated as neonates (in the first 48 h of life) with capsaicin (50 micrograms/kg, s.c.) were compared to age-matched neonatal vehicle-treated controls. Whereas the i.v. administration of 5-HT produced a dose-dependent (6-96 micrograms/kg, i.v.) inhibition of the nociceptive TF reflex (ED50 = 48.1 +/- 11.3 micrograms/kg; n = 7) and distinct pseudaffective responses (usually by 24-48 micrograms/kg) in vehicle-treated rats, 5-HT (6-192 micrograms/kg, i.v.) failed to significantly alter TF latency or produce pseudaffective behaviors in the capsaicin-treated rats (n = 10). There was no difference in baseline TF latencies between the two groups. There were essentially no differences between vehicle- and capsaicin-treated rats with respect to the initial cardiopulmonary vagal afferent-mediated (Bezold-Jarisch reflex) decreases in heart rate and arterial blood pressure or the subsequent pressor phase. However, the magnitude of the late hypotensive phase was significantly greater in capsaicin-treated rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Antinociception produced by electrical stimulation of vagal afferents: independence of cervical and subdiaphragmatic branches.

Expt. 1 showed that electrical stimulation of either the main dorsal or ventral branch of the subdiaphragmatic vagus could produce inhibition of the nociceptive tail-flick reflex in lightly anesthetized rats. The antinociception produced by electrical stimulation of the dorsal subdiaphragmatic vagus was eliminated by resection of the right cervical vagus, but relatively unaffected by resection of the left cervical vagus. The opposite effects for cervical vagal resection were obtained with electrical stimulation of the ventral branch of the subdiaphragmatic vagus. These results indicate that the antinociceptive effects of subdiaphragmatic vagal stimulation are mediated via uncrossed afferents traveling in the cervical vagus to activate an inhibitory spinopetal system. These findings are consistent with the established anatomy of vagal afferents. Expt. 2 showed that degeneration of the dorsal subdiaphragmatic vagus did not alter the threshold intensity of right cervical vagal stimulation necessary to produce inhibition of the tail-flick reflex. These results demonstrate that the antinociceptive effects of cervical vagal stimulation are primarily due to activation of the cardiopulmonary component of the nerve, rather than the subdiaphragmatic component. The second experiment also demonstrated that the subdiaphragmatic branch of the vagus can be selectively degenerated with ricin while leaving the cervical branch intact, even though the cell bodies of both sets of afferents are located within the nodose ganglion. These data are discussed in terms of vagal afferents and their role in the modulation of nociceptive transmission.

Animals↗
PubMed1991

Gastrin-releasing peptide gene products in midtrimester human fetal lung with and without maternal smoking history during pregnancy.

A preliminary morphological study on human fetal lungs with positive maternal smoking history demonstrated alterations of the neuroepithelial bodies (NEBs). We studied human fetal lung tissue between the gestational ages of 12 weeks and 19 weeks, comprising 12 cases with a smoking history during pregnancy (Group 1) and eight cases without a smoking history during pregnancy (Group 2). We demonstrated, by immunocytochemistry, the presence of gastrin-releasing peptide (GRP) gene products: GRP 14-27 in all 20 cases, and C terminal peptide of pro-GRP (C-flanking peptide) in 17 cases. Quantification of the neuroepithelial cells (NECs) was made by computer-enhanced image analysis using the Context Vision system, expressing 1) the total stained areas of the NECs per unit area of section and 2) the total staining areas of the NECs per unit area of airway epithelium, measured as the area of cytokeratin immunoreactivity in an adjacent section. The results show no statistically significant difference between groups 1 and 2 for either GRP 14-27 or C-flanking peptides. The apparent lack of influence of maternal smoking during pregnancy on the expression of GRP gene products in the NECs could be a reflection of inherently reduced reactivity of the cells during the gestation period studied. However, a larger series is needed before any conclusions can be made. Alternatively, the adverse effects of smoking might be reflected during the canalicular phase of lung development; an increased immunoreactivity appears to be present during that period. The expression of pro-GRP gene products in the pulmonary NECs of older fetuses and neonates with maternal smoking history during pregnancy requires further study.

Female↗
PubMed1991

Segmental wall motion abnormalities in the absence of clinically documented myocardial infarction: clinical significance and evidence of hibernating myocardium.

To determine the frequency and significance of left ventricular wall motion abnormalities in patients without clinical evidence of myocardial infarction, we reviewed the two-dimensional echocardiograms of 252 patients who had no history or electrocardiographic evidence of myocardial infarction and who subsequently underwent coronary angiography. Seventy-seven patients (31%) had one or more segmental wall motion abnormalities. Sixty-six of the 77 patients (86%) had significant coronary artery disease (greater than or equal to 50% luminal diameter stenosis). Seventy-four percent of the patients with coronary artery disease had multivessel disease. The left ventricle was divided into anterior and posterior regions. In the 66 patients, there were 77 separate regions with wall motion abnormalities (49 hypokinesis, 22 akinesis, 6 dyskinesis), including 60 regions (78%) supplied by coronary vessels with greater than or equal to 70% stenosis. Thirty-two patients underwent coronary artery bypass surgery or percutaneous transluminal coronary angioplasty. Follow-up echocardiograms were obtained in 19 patients who had wall motion abnormalities involving 22 regions. Twenty of the 22 regions were revascularized. Wall motion improved in 17 of 20 regions (85%) and returned to normal in 15 regions (75%). We conclude that segmental wall motion abnormalities may be detected by echocardiography in up to one third of patients evaluated for suspected coronary artery disease without documented myocardial infarction. These abnormalities are associated with a high likelihood of multivessel disease as well as with significant narrowing of the artery supplying the region demonstrating abnormal wall motion. Improvement in segmental wall motion abnormalities after revascularization suggests that these areas represent regions of hibernating myocardium.

Adult↗
PubMed1991

Survey of the incidence of Listeria monocytogenes and other Listeria spp. in experimentally irradiated and in matched unirradiated raw chickens.

Listeria spp. were sought in 32 chickens experimentally irradiated (2.5 kGy) and in 25 matched unirradiated chickens. Using the modified Food and Drug Administration method only three of the chickens were positive for L. monocytogenes. Using the more sensitive cold enrichment method 30 were found positive. The proportion of carcasses contaminated with L. monocytogenes was lower in the irradiated birds than in the unirradiated birds. The results also indicated that the numbers of L. monocytogenes in the irradiated birds were lower than in the unirradiated birds. The only other species of Listeria isolated was L. innocua, which was found on 44% of unirradiated chickens, but on none of the irradiated chickens.

Animals↗
PubMed1991

Comparison of a cold enrichment and the FDA method for isolating Listeria monocytogenes and other Listeria spp. from ready-to-eat food on retail sale in the U.K.

A cold enrichment and the modified FDA selective enrichment method were compared for their ability to detect Listeria monocytogenes and other Listeria species from various ready-to-eat foods on sale in the UK. Of 57 food samples examined using cold enrichment, five yielded L. monocytogenes, and two L. innocua. The FDA enrichment method yielded three samples positive for L. monocytogenes only. Foods examined included soft cheeses, fermented meat sausages, pates and salads.

Animals↗
PubMed1991

Vascular tone influences arterial pressure lability after sinoaortic deafferentation.

Sinoaortic deafferentation (SAD) results in increased variability of arterial pressure. The purpose of this study was to investigate the contribution of nonneurogenic, peripheral vasomotor mechanisms to this arterial pressure lability. In rats with SAD, ganglionic blockade combined with either captopril or a V1-vasopressin receptor antagonist reduced the high lability. Under these conditions, continuous infusions of phenylephrine and the endogenous vasoconstrictors angiotensin II, epinephrine, and vasopressin increased lability, suggesting that the level of vascular tone is important for maintaining lability. Hemodynamic changes in individual vascular beds did not correlate with pressure lability; however, the sum of the changes in resistance, an estimate of changes in total peripheral resistance, was significantly correlated. These results suggest that 1) direct actions of endogenous vasoconstrictors can induce marked variations of arterial pressure, presumably by sustaining a high background of vascular tone, and 2) variations in resistance of individual vascular beds do not account for the lability of arterial pressure evoked by infusion of vasoconstrictors. We conclude that vascular tone of neural and/or humoral origin is critical for the generation of fluctuations in arterial pressure associated with deafferentation of baroreceptors.

Afferent Pathways↗
PubMed1991

Role of sympathetic nerve activity in the generation of vascular nitric oxide in urethane-anesthetized rats.

The aim of the present study was to examine the involvement of the sympathetic nervous system in the generation or release of vascular nitric oxide. In urethane-anesthetized rats, the administration of the novel nitric oxide synthesis inhibitor L-N-nitro arginine (LNA) (0.02 mmol/kg i.v.) increased mean arterial pressure and renal, mesenteric, and hindquarter vascular resistances. The intravenous administration of L-arginine (60 mg/kg plus 12 mg/kg/min i.v.) produced small reductions in arterial pressure and vascular resistances and abolished the hemodynamic effects of LNA. Pretreatment with the ganglion blocking agent chlorisondamine lowered mean arterial pressure and vascular resistances, abolished the LNA-induced pressor and renal vasoconstrictor response, and attenuated the increases in mesenteric and hindquarter resistances. In contrast, the vasodilator hydralazine lowered mean arterial pressure and vascular resistances to levels equivalent to that of ganglionic blockade; however, the subsequent administration of LNA still produced significant increases in arterial pressure and regional vascular resistances. In ganglion-blocked rats in which pressure and vascular resistances were returned to normal levels by infusion of arginine vasopressin or phenylephrine, the pressor and vasoconstrictor effects of LNA were restored. However, phenylephrine was significantly more efficacious and markedly exaggerated the action of LNA. These results suggest that the sympathetic nervous system plays an important role in modulating the synthesis or release of vascular nitric oxide through the effects of 1) normal sympathetic discharge, 2) humoral activation of alpha-adrenergic receptors, and 3) vascular tone per se.

Animals↗
PubMed1991

Central nervous system and the pathogenesis of hypertension. Sites and mechanisms.

A large body of evidence indicates that the central nervous system plays an essential role in the pathogenesis of hypertension. However, in many cases the specific brain regions involved and the mechanisms by which these regions promote hypertension are not known. In recent years, research in this and other laboratories has attempted to determine the mechanisms by which neural and humoral signals arising in response to pathological conditions (often occurring in the periphery) interact with the central nervous system to produce hypertension. In this article, we illustrate the coupling of peripheral and central factors in the pathogenesis of hypertension by examining the central actions of angiotensin II and mineralocorticoids in the expression of renal hypertension and mineralocorticoid-salt hypertension, respectively. We also review recent data from this laboratory illustrating the involvement of medullary vasomotor centers in the development of neurogenic hypertension after sinoaortic deafferentation and in the maintenance of hypertension in the spontaneously hypertensive rat.

Animals↗