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Biomedical subjects

S J Lewis

Publications and source records attributed to S J Lewis.

At least 127 records · Page 7Linked to original sources
PubMed1995

Modulation of baroreceptor activity by nitric oxide and S-nitrosocysteine.

The goal of this study was to determine whether nitric oxide (NO) and the NO donor, S-nitrosocysteine (cysNO), modulate the activity of carotid sinus baroreceptors. Baroreceptor activity was recorded from the vascularly isolated carotid sinus in anesthetized rabbits. Baroreceptor activity decreased in a dose-dependent manner after injection of either NO or cysNO as constant pressure was maintained, and activity recovered spontaneously over time, within seconds to minutes. The baroreceptor pressure-activity relation was shifted significantly to the right by cysNO, with a profound suppression of activity at high pressure. Baroreceptor activity at 160 mm Hg averaged 76 +/- 8%, 60 +/- 6%, and 36 +/- 5% of the control maximum during exposure to 10(-4), 2 to 3 x 10(-4), and 10(-3) mol/L cysNO, respectively. The inhibition of activity by the L and D isomers of cysNO was equivalent and was blocked by reduced hemoglobin, suggesting that the effect was mediated by NO. The suppression of baroreceptor activity by cysNO was not related to vascular relaxation as measured by videomicrometer. Inhibition of soluble guanylate cyclase with methylene blue or 6-anilinoquinoline-5,8-quinone (LY83583, 10(-5) mol/L) did not attenuate and dibutyryl cGMP (10(-3) mol/L) did not mimic the suppression of baroreceptor activity by cysNO, suggesting a cGMP-independent mechanism. Activation of endogenous NO formation with thimerosal (10(-5) to 10(-4) mol/L) reduced maximum baroreceptor activity in five of eight experiments to 59 +/- 7% of the control maximum.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Crystal structure of an extracellular fragment of the rat CD4 receptor containing domains 3 and 4.

BACKGROUND: CD4 is a transmembrane protein on the surface of T lymphocytes that interacts with MHC class II proteins at the surface of accessory cells, and is involved in the triggering of the lymphocytes by foreign antigens. It is also the major receptor for the human immunodeficiency virus. The extracellular portion of CD4 was predicted to contain four immunoglobulin superfamily domains and this has been confirmed by X-ray crystallography, but no detailed structure of domains 3 and 4 has been available. RESULTS: We now report the expression of a form of rat CD4 containing only domains 3 and 4, its crystallization, and the refinement and analysis of its structure by X-ray crystallography with 2.6 A spacing data. Both domains show variations in core residues when compared with immunoglobulin domains. Features of the structure are discussed with respect to the structure of the complete extracellular part of CD4 and its function. CONCLUSIONS: Domains 3 and 4 of CD4 show considerable similarity to domains 1 and 2, although there is a 25 degrees rotation in the relative positions of the domains with respect to one another. The absence of the disulphide bond in domain 3 is associated with an alteration in the packing of the beta-sheets, which may be important for interactions with domain 2 in the overall receptor structure. The location of N-linked glycosylation on one face of domain 3 appears to preclude the dimerization that is observed in antibodies.

Amino Acid Sequence↗
PubMed1994

Effects of sinoaortic baroreceptor denervation on depletion-induced salt appetite.

This study examined the effects of denervation of the carotid sinus and aortic arch baroreceptors on sodium depletion-induced salt appetite in rats. Depletion of extracellular fluid began with two injections of furosemide (10 mg/kg sc), 30 min apart, and removal of all ambient sodium from the cages. Water and sodium-deficient chow were available overnight. The next morning, access to 0.3 M NaCl was provided, and intakes of water and saline were measured every 30 min for 2 h and again at 24 h. Three such tests were administered. Groups of sham and sinoaortic baroreceptor-denervated (SAD) rats had equivalently negative water and sodium balances before access to saline the next morning. Sham-denervated rats drank sufficient saline in 2 h to achieve positive sodium balance and subsequently ingested sodium in excess of need for another 22 h. SAD rats drank half as much saline as sham-denervated rats by 2 and 24 h and remained in negative balance at 2 h. Sham-denervated rats increased their intakes of saline solution with repeated tests, but SAD rats did not. These findings suggest that arterial baroreceptors provide critical neural input for the normal expression of salt appetite.

Animals↗
PubMed1994

Nitrosyl factors mediate active neurogenic hindquarter vasodilation in the conscious rat.

Exposure to noxious environmental stimuli such as air-jet stress (AJS) produces a pattern of hemodynamic changes referred to as the "defense reaction". In the rat these changes include a relatively modest increase in mean arterial blood pressure (MAP), tachycardia, renal and mesenteric vasoconstriction, and a marked hindquarter vasodilation. The aim of the present study was to determine whether the AJS-induced decrease in hindquarter resistance is mediated by a sympathetic neurogenic vasodilator system that uses nitric oxide (NO) and/or related nitrosyl factors. AJS produced a small, rapid increase in MAP, which quickly returned to baseline (within 5 seconds), and a substantial increase in hindquarter blood flow and decrease in hindquarter resistance, which occurred almost instantaneously (1 to 2 seconds) and were sustained for at least 30 seconds. The intravenous injection of either bretylium (5 mg/kg), which prevents impulse propagation-mediated release of neurotransmitters/neuromodulators from sympathetic terminals, or NG-nitro-L-arginine methyl ester (L-NAME, 25 mumol/kg), which blocks NO synthesis, essentially abolished the AJS-induced increase in hindquarter blood flow and fall in hindquarter resistance. In contrast, the hindquarter vasodilation produced by the NO donor sodium nitroprusside (4 micrograms/kg i.v.) was markedly exaggerated in the bretylium- or L-NAME-treated rats. We also found that rat lumbar sympathetic fibers projecting to the hindquarter vasculature contain NADPH diaphorase, a marker for NO synthase in paraformaldehyde-perfused tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

'Atypical' bacteria are a common cause of community-acquired pneumonia in hospitalised adults.

OBJECTIVES: To assess the proportion of cases of community-acquired pneumonia caused by 'atypical' bacteria, including the recently discovered Chlamydia pneumoniae, and to compare the clinical, radiographic and laboratory features of patients with and without 'atypical' bacteria. METHODS: A prospective serological study was carried out on consecutive adult pneumonia patients from July 1987 to July 1988. Acute and convalescent sera were tested in batches for antibodies against Legionella pneumophila serogroup 1, C. pneumoniae, Chlamydia psittaci, Coxiella burnetii (phase-2 antigen) and Mycoplasma pneumoniae (IgG and IgM). Records and chest radiographs were examined retrospectively. RESULTS: Acute and convalescent sera were available from 113 patients. The records of 4 patients could not be traced and 17 patients did not fulfil the inclusion criteria. Thirty-two of these 92 patients (35.9%) were found to be infected with 'atypical' bacteria. The two most common organisms were C. pneumoniae (20.7%) and L. pneumophila (8.7%). There were no differences in the clinical and radiographic features of patients with and without 'atypical' bacteria. Clinicians prescribed erythromycin or tetracyclines with equal frequency in the two groups. CONCLUSIONS: 'Atypical' bacteria, especially C. pneumoniae, are a common cause of community-acquired pneumonia in adults in South Africa. This is the first demonstration of an aetiological role of C. pneumoniae in this country. We confirmed the finding of other studies that there are no clinical, radiographic or laboratory features characteristic of 'atypical' bacterial infection in hospitalised patients. This has major implications for therapy, as these organisms respond to erythromycin and tetracyclines, but not to beta-lactam antibiotics.

Adult↗
PubMed1994

Malignant lymphoma of bone.

OBJECTIVE: To evaluate the diagnosis and management of patients with malignant lymphoma of bone. DESIGN: A case series review in which the minimum follow-up was 24 months and the mean follow-up was 49 months. SETTING: All patients were managed at a tertiary care centre, although initial biopsies were often done in community centres. PATIENTS: Selected for review were 15 of 18 consecutive patients who were referred to the Musculoskeletal Oncology Unit at the Mount Sinai Hospital, Toronto, between 1984 and 1989, with a bone lesion as the presenting symptom of lymphoma. The three excluded patients included two with diffuse nodal disease at presentation and one who had a second, unrelated malignant tumour. INTERVENTIONS: Staging studies (hematologic investigations, radiography, technetium bone scanning and computed tomography), surgical biopsies of the lesion, chemotherapy, radiotherapy and in some cases surgical resection of the lesion. MAIN OUTCOME MEASURES: The number of biopsies required for diagnosis and the incidence of complications that required operative intervention. RESULTS: Seven of the 15 patients required more than one biopsy to establish the diagnosis. Five patients required surgical procedures for late complications that included pathologic fractures, wound infection and osteonecrosis. At 24 months' follow-up, 13 patients were disease free and 2 had died. CONCLUSIONS: Proper biopsy and pathological evaluation are crucial in the diagnosis of lymphoma of bone. These measures will decrease the necessity for repeat biopsies. Lymphoma is best managed medically. Surgery should be reserved for biopsy and for treatment of the complications of therapy.

Adolescent↗
PubMed1993

Cardiovascular effects produced by systemic injections of nitro blue tetrazolium in the rat.

Nitro blue tetrazolium is a powerful electron acceptor which is widely used to localize NADPH-dependent flavin-containing enzymes known as NADPH diaphorases. By accepting electrons, nitro blue tetrazolium is known to inhibit the activity of these enzymes. The present study examined the effects of intravenous nitro blue tetrazolium on arterial blood pressure and regional blood flows in urethane-anesthetized rats. Nitro blue tetrazolium (0.1-5 mol/kg) produced a dose-dependent hypotension and differential effects on regional hemodynamics including decreases in hindquarter and mesenteric vascular resistances and a marked increase in renal resistance. These results demonstrate that systemic administration of nitro blue tetrazolium produces profound hemodynamic effects, the mechanisms of which remain to be elucidated.

Anesthesia↗
PubMed1993

Spermidine and cardiovascular control in nucleus tractus solitarii in rat.

Cardiovascular effects elicited by unilateral microinjection of polyamines into the nucleus tractus solitarii (NTS) were tested in anesthetized rats. Spermidine (50-900 pmol) produced dose-dependent depressor and bradycardiac responses that were similar to those elicited by N-methyl-D-aspartate (NMDA; 0.1-1.2 pmol). The polyamines, putrescine and spermine, did not produce significant cardiovascular responses. The cardiovascular responses induced by spermidine and NMDA were almost eliminated by prior injection of the noncompetitive NMDA antagonist MK801 into NTS. On the other hand, a competitive antagonist 2-amino-5-phosphonovaleric acid (APV) blocked responses to NMDA but only attenuated those to spermidine. These findings support an action of the polyamine spermidine at the NMDA receptor complex in NTS where it could participate in modulating cardiovascular activity.

2-Amino-5-phosphonovalerate↗
PubMed1993

Out-of-hospital resuscitation in East Sussex: 1981 to 1989.

OBJECTIVE: To assess the impact of extended training in advanced life support on the outcome of resuscitation. DESIGN: Analysis of the successful resuscitations from 1981 to 1989. SETTING: Brighton and East Sussex. RESULTS: 248 patients were resuscitated from cardiac or respiratory arrest in the community and subsequently survived to leave hospital. Their mean age was 64 years and one year survival was 77%. In most cases the cause of collapse was cardiac but 38 (15%) suffered a respiratory arrest. In 140 of the successful resuscitations (56%) collapse occurred before the arrival of the ambulance. Basic life support, with ventilation and chest compression where necessary, was sufficient to revive 35 (14%) of the patients. Defibrillation was also required in 107 patients (43%), and in a further 106 patients (43%) who had prolonged cardiorespiratory arrest requiring endotracheal intubation and the use of several drugs. Review of ambulance forms and case notes showed that in 87 cases (35%) the abilities of the paramedical ambulance staff in advanced resuscitation techniques contributed decisively to the success of resuscitation. These skills are illustrated by eight case reports. CONCLUSIONS: Extended training for ambulance staff increases the likelihood of successful resuscitation from out-of-hospital cardiopulmonary arrest. Though instruction in defibrillation must have the highest priority, full paramedical training can bring appreciable additional benefits.

Adolescent↗
PubMed1993

Role of arteria baroreceptor input on thirst and urinary responses to intracerebroventricular angiotensin II.

Intracerebroventricular (icv) infusion of angiotensin II (ANG II) in rats elicits greater water intake under hypotensive, compared with normotensive, conditions. The present experiments used sinoaortic baroreceptor-denervated (SAD) rats and sham-operated rats to examine if the modulatory effects of arterial blood pressure on water intake in response to icv ANG II are mediated by arterial baroreceptors. Mean arterial blood pressure (MAP) was raised or lowered by intravenous (i.v.) infusions of phenylephrine (1 or 10 micrograms.kg-1 x min-1) or minoxidil (25 micrograms.kg-1 x min-1), respectively. The angiotensin-converting enzyme inhibitor captopril (0.33 mg/min) was infused i.v. to prevent the endogenous formation of ANG II during testing. Urinary excretion of water and solutes was measured throughout. Water intake elicited by icv ANG II was inversely related to changes in MAP. Specifically, rats drank more water in response to icv ANG II when MAP was reduced by minoxidil but drank less water when MAP was elevated by phenylephrine. The influence of changing MAP on the icv ANG II-induced drinking responses was not affected by SAD. These results suggest that the modulatory effects of arterial blood pressure on icv ANG II-induced drinking can occur in the absence of sinoaortic baroreceptor input.

Angiotensin II↗
PubMed1993

Role of periaqueductal gray in the pressor response produced by central injections of angiotensin II.

The present studies were undertaken to determine the role of rostral periaqueductal gray (PAG) in mediating the pressor effect produced by intracerebroventricular (icv) injection of angiotensin II (ANG II, 200 ng). Two functionally and anatomically distinct sites were identified in rostral PAG: a dorsomedial site involved in the hemodynamic responses produced by electrical stimulation of the anteroventral third ventricle (AV3V) region and a ventromedial site required for the pressor response elicited by icv administration of ANG II. In Saffan-anesthetized rats, injection of lidocaine (LIDO, 4%) in dorsomedial PAG, but not in ventromedial PAG, significantly attenuated the decrease in hindquarter resistance (HQR) produced by electrical stimulation of the AV3V region, and the poststimulatory increase in mean arterial pressure (MAP) and HQR. The injection of LIDO in ventromedial PAG had no effect on the hemodynamic responses produced by electrical stimulation of the AV3V region in anesthetized rats but significantly attenuated the pressor response produced by icv administration of ANG II in conscious rats. The hypothesis that these two sites receive separate projections was addressed by microinjecting two retrogradely transported fluorescent dyes, Fluoro-Gold and Fast Blue. The anatomic findings suggest that separation of the pathways activated by electrical and chemical stimulation of the AV3V region occurs at the level of rostral PAG.

Angiotensin II↗
PubMed1993

Trends in cardiac care: contractions, concentration, collaboration.

Cardiovascular services is entering an age of contraction and concentration. The number of programs and the growth in inpatient procedures have topped out and the presence of significant excess capacity has become apparent. During the next five years, there will be heightened pressures to simultaneously decrease the overall number of cardiac procedures performed and, on the part of individual providers, increase procedure volume in order to achieve economies of scale and high levels of quality. It is likely that the number of health care organizations with OHS programs and PTCA may be cut to 500 by the year 2000, significantly influencing the redistribution of cardiac services along regional lines. The public, government, and private payers have embarked on a quest for value; and in the future they will only purchase services from providers demonstrating high-quality outcomes and average, or below average, charges. HCFA's Cooperative Cardiovascular Project is typical of the direct continuous quality improvement and management initiatives that will be implemented to monitor appropriateness, outcome quality, and resource utilization through the application of clinical practice guidelines (CPGs) and data on the treatment of AMI, PTCA, and CABG surgery. A more indirect, managed care approach by purchasers to obtaining higher value can be seen in the Medicare Participating Heart Bypass Center Demonstration project, the federal government's first big step into selective specialty care contracting for clinical service on a package price basis. Several different types of private initiatives have been used to achieve wider distribution of service while maintaining high program volumes and high-quality care through collaboration and the formation of interhospital linkages. Although some of these have included collaborative programs to encourage voluntary community-based planning and discourage the duplication of services, the payers demand for value (cost/quality) and the organizational leverage of the regional health alliances will accelerate the process and spur the formation of a smaller number of high-volume invasive programs. Large invasive programs will continue to formalize interhospital linkages to provide an integrated set of services in a layered system of cardiac care.(ABSTRACT TRUNCATED AT 400 WORDS)

Cardiac Catheterization↗
PubMed1992

Severity of imported falciparum malaria: effect of taking antimalarial prophylaxis.

OBJECTIVE: To investigate the effects of antimalarial chemoprophylaxis and other variables on the severity of falciparum malaria. DESIGN: Review of consecutive malaria cases between 1987 and 1991. SETTING: The Hospital for Tropical Diseases, London. SUBJECTS: 250 consecutive cases of mild and 51 consecutive cases of severe falciparum malaria. RESULTS: Prophylaxis was taken in 52.4% (131/250) of the cases of mild malaria and 21.6% (11/51) of cases of severe malaria. Severe malaria was more common in white patients than in those of African origin and was also seen more commonly in people returning from central, southern, and east Africa than in those returning from west Africa. Patients with severe malaria presented sooner than patients with mild malaria. CONCLUSIONS: Prior chemoprophylaxis led to a reduction in the severity of falciparum malaria. Ethnic origin, time to presentation, and sex were also associated with the severity of malaria.

Adult↗
PubMed1992

Age, strain and anesthetic dependent differences in the nociceptive responses produced by i.v. 5-HT in the rat.

The intravenous (i.v.) administration of serotonin (5-HT) to rats is a noxious visceral stimulus which produces distinct vagal afferent-mediated pseudaffective responses, a passive avoidance behavior, a vagal afferent-mediated inhibition of the tail-flick (TF) reflex and a complex cardiovascular response. In the present study, we examined the effects of age (10 or 16 weeks), strain (Sprague-Dawley, SD; Wistar-Kyoto, WKY; spontaneously hypertensive rats, SHR) and anesthetic (conscious or lightly pentobarbital-anesthetized) on nociceptive (TF reflex and pseudaffective responses) and cardiovascular responses produced by 5-HT (3-288 micrograms/kg, i.v.). There were no age-related differences in baseline TF latencies in the 3 strains. Further, latencies were generally not significantly different whether rats were tested conscious or lightly anesthetized. There were, however, strain differences. Both conscious or lightly pentobarbital-anesthetized SHR and WKY rats at 10 weeks of age had significantly faster response latencies than 10 week old SD rats. At 16 weeks of age, only the lightly pentobarbital-anesthetized WKY and SHR showed faster response latencies than SD rats. The WKY and SHR, but not the SD rats, were more sensitive to the nociceptive effect of i.v. 5-HT at 16 weeks of age compared to 10 weeks of age. At both ages, WKY and SHR, but not SD rats, showed an anesthetic-dependent increase in nociceptive sensitivity to i.v. 5-HT. In addition, at both ages, regardless of the presence of anesthetic, the order of sensitivity to the nociceptive effects of i.v. 5-HT was SD greater than WKY much much greater than SHR.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗