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Biomedical subjects

S J Lewis

Publications and source records attributed to S J Lewis.

At least 37 records · Page 2Linked to original sources
PubMed2001

Effects of chronic lesions of the anteroventral region of the third ventricle on cardiac beta-adrenoceptor function in conscious rats.

This study examined whether cardiac beta-adrenoceptor (beta-AR) function was altered in conscious rats with lesions surrounding the anteroventral third ventricle (AV3V). The findings were: (1) beta(1,2)-AR-mediated tachycardia was similar in sham and AV3V-lesion rats, (2) beta(3)- and/or atypical beta-AR-mediated tachycardia elicited by isoproterenol (10 microg/kg, i.v.; ISO) was diminished in AV3V-lesion rats treated with beta(1,2)-AR antagonists, but was not in similarly-treated sham-lesion rats, and (3) the tachycardia elicited by the membrane permeable cAMP-analogue, 8-(4-chlorophenylthiol)-cAMP (10 micromol/kg, i.v.), was similar in AV3V- and sham-lesion rats. The possibility that increased plasma sodium/osmolality in AV3V-lesion rats down-regulated cardiac beta(3)- and/or atypical beta-ARs, but not beta(1,2)-ARs or intracellular cAMP signaling is discussed.

Adrenergic beta-Agonists↗
PubMed2001

Devolution to democratic health authorities in Saskatchewan: an interim report.

BACKGROUND: In 1995 Saskatchewan adopted a district health board structure in which two-thirds of members are elected and the rest are appointed. This study examines the opinions of board members about health care reform and devolution of authority from the province to the health districts. METHODS: All 357 members of Saskatchewan district health boards were surveyed in 1997; 275 (77%) responded. Analyses included comparisons between elected and appointed members and between members with experience as health care providers and those without such experience, as well as comparisons with hypotheses about how devolution would develop, which were advanced in a 1997 report by another group. RESULTS: Most respondents felt that devolution had resulted in increased local control and better quality of decisions. Ninety-two percent of respondents believed extensive reforms were necessary and 83% that changes made in the previous 5 years had been for the best. However, 56% agreed that there was no clear vision of the reformed system. A small majority (59%) perceived health care reform as having been designed to improve health rather than reduce spending, contrary to a previous hypothesis. Many respondents (76%) thought that boards were legally responsible for things over which they had insufficient control, and 63% perceived that they were too restricted by rules laid down by the provincial government, findings that confirm the expectation of tensions surrounding the division of authority. Respondents with current or former experience as health care providers were less likely than nonprovider respondents to believe that nonphysician health care providers support decisions made by the regional health boards (45% v. 63%, p = 0.02), a result that confirmed the contention that the role of health care providers on the boards would be a source of tension. INTERPRETATION: Members of Saskatchewan district health boards supported the general goals of health care reform and believed that changes already undertaken had been positive. There were few major differences in views between appointed and elected members and between provider and nonprovider members. However, tensions related to authority and representation will require resolution.

Adult↗
PubMed2001

Soft tissue sarcomas involving the pelvis.

BACKGROUND AND OBJECTIVES: Soft tissue sarcomas (STS) of the true pelvis are rare tumors and there is little information in the literature related to pelvic STS. The purposes of this review were to understand the anatomic extension of these tumors to better plan surgical treatment and to determine the outcome of these patients. METHODS: Eighteen consecutive patients presenting between 1987 and 1995 with soft tissue sarcomas involving the true pelvis were retrospectively reviewed at minimum follow-up of 18 months. Cross-sectional imaging was reviewed for each patient to determine the anatomical location of the lesions. RESULTS: The tumors were confined to the true pelvis in 4 patients, extended to the retroperitoneum in three cases, and extended to the thigh in 11 patients. Adjuvant radiation was administered to all but 2 patients who had received radiation to the region in the past and all patients underwent surgical resection (local resection in 13 patients and hindquarter amputation in 5 patients). Surgical resection had a high rate of morbidity and complications including positive resection margins in nine individuals. Of the 18 patients, 11 died at a mean time of 15.5 (2-58) months from surgery, 4 were alive with evidence of disease at a mean time of 44.3 (18-68) months, and 3 were alive with no evidence of disease at a mean time of 57 (43-71) months. CONCLUSIONS: Soft tissue sarcoma of the pelvis is fortunately a rare disease with a high risk of local and systemic disease progression despite treatment with irradiation and surgical resection.

Adult↗
PubMed2001

Polymorphisms in the NAD(P)H: quinone oxidoreductase gene and small cell lung cancer risk in a UK population.

NAD(P)H: quinone oxidoreductase (NQO1) protects the cell against cytotoxicity by reducing the concentration of free quinone available for single electron reduction. The NQO1 gene is polymorphic and the variant protein exhibits just 2% of the enzymatic activity of the wildtype protein. In this study, we investigated NQO1 genotype in relation to lung cancer risk in patients attending a Manchester bronchoscopy clinic. The cases were patients with a current, or history of, malignant tumour of the lung, trachea or bronchus. The control group were all other patients attending the clinic who had never been diagnosed with a tumour. DNA extraction from bronchial lavage or blood samples and genotyping was successfully carried out for 82 of the cases and 145 controls. Patients carrying at least one variant allele were found to have almost a 4-fold increased risk of developing small cell lung cancer (adjusted OR=3.80, 95% C.I. 1.19-12.1). No association between NQO1 genotypes and non-small cell lung cancer risk was found. Furthermore, the excess small cell lung cancer risk associated with non-wildtype NQO1 genotypes was only apparent in heavy smokers where there was a >10-fold increased risk (adjusted OR=12.5, 95% C.I. 2.1-75.5). These results suggest that the NQO1 protein may be involved in the detoxification of those carcinogens associated with the development of small cell lung cancer. Individuals with reduced enzyme activity, due to a polymorphism in this gene, may therefore have an increased risk of developing this disease.

Aged↗
PubMed2001

Osteoporosis prevention in myasthenia gravis: a reminder.

OBJECTIVES: Consensus guidelines for bone management of patients taking corticosteroids suggest two main interventions: Dual energy X-ray absorptiometry (DEXA) scanning in those taking prednisolone > or =7.5 mg daily for > or =6 months (repeated every 1-3 years as indicated). Bisphosphonate therapy for those taking prednisolone > or =15 mg daily for > or =6 months regardless of DEXA result, and also for patients with known or high risk of developing osteoporosis (including those aged >65 years). MATERIAL AND METHODS: We audited adherence to these guidelines in all adults with myasthenia gravis (MG) attending our neurology service. RESULTS: Of 80 patients with MG (47 male, mean age 63.3 years), 34 (43%) had received corticosteroids for > or =6 months. Eighteen were taking prednisolone > or =7.5 mg daily (mean dose 16.6 mg) yet only 4 of these (22%) had undergone DEXA scanning. Of the 13 patients meeting the guideline criteria to receive bisphosphonate therapy, this was prescribed to only 7 (54%). Two others were prescribed vitamin D, 2 a calcium supplement and 2 were receiving no prophylaxis. CONCLUSION: In these MG patients the guidelines were followed in only a minority. Neurologists need greater awareness of the bone health consequences of prescribing long-term corticosteroids.

Adrenal Cortex Hormones↗
PubMed2001

Effect of an enteric-release formulation of naloxone on intestinal transit in volunteers taking codeine.

INTRODUCTION: Constipation is a common side-effect of opioid therapy; in addition to their analgesic effect, opioids reduce intestinal secretion and motility with an increase in whole-gut transit time. Naloxone, a specific opioid antagonist, reverses these effects but may also cause symptoms of opioid withdrawal in patients on long-term therapy. AIM: To use an enteric-release formulation, designed to produce a topical effect in the gut, with minimum systemic effects. METHODS: Naloxone 10 mg b.d. and codeine 30 mg b.d. were used with identical placebo capsules in four sets of studies; 12 male volunteers were given the drugs alone and in combination, with a control study involving double placebo, during each of four study periods. Whole-gut transit time was calculated and compared for each treatment period. RESULTS: Naloxone, both alone and with codeine, significantly shortened the mean whole-gut transit time compared with the control period, respectively, from 53.1 to 42.1 h (P=0.005) and to 40.7 h (P=0.024). Urgency to defecate was reported by two volunteers on naloxone alone and by three on combination therapy. CONCLUSIONS: The results show that the naloxone formulation counteracts the effect of codeine on intestinal transit, suggesting that it may have useful clinical applications.

Administration, Oral↗
PubMed2001

Guidelines for adults on self-medication for the treatment of acute diarrhoea.

Acute uncomplicated diarrhoea is commonly treated by self-medication. Guidelines for treatment exist, but are inconsistent, sometimes contradictory, and often owe more to dogma than evidence. An ad hoc multidisciplinary group has reviewed the literature to determine best practice. In general it is recognized that treatment of acute episodes relieves discomfort and social dysfunction. There is no evidence that it prolongs the illness. Self-medication in otherwise healthy adults is safe. Oral loperamide is the treatment of choice. Older anti-diarrhoeal drugs are also effective in the relief of symptoms but carry the risk of unwanted adverse effects. Oral rehydration solutions do not relieve diarrhoea, and confer no added benefit for adults who can maintain their fluid intake. Probiotic agents are, at present, limited in efficacy and availability. Antimicrobial drugs, available without prescription in some countries, are not generally appropriate for self-medication, except for travellers on the basis of medical advice prior to departure. Medical intervention is recommended for the management of acute diarrhoea in the frail, the elderly (> 75 years), persons with concurrent chronic disease, and children. Medical intervention is also required when there is no abatement of the symptoms after 48 h, or when there is evidence of deterioration such as dehydration, abdominal distension, or the onset of dysentery (pyrexia > 38.5 degrees C and/or bloody stools).

Acute Disease↗
PubMed2001

Treatment of spinal stenosis and fixed sagittal imbalance.

Most commonly, sagittal imbalance associated with stenosis is seen with a hypolordotic fusion mass, junctional kyphosis, and junctional stenosis. If the deformity is flexible, it can be treated with anterior and posterior fusion with anterior structural grafting. If it is fixed, which it usually is, then a pedicle subtraction procedure with decompression and extension of the fusion usually is the most suitable operative approach.

Adult↗
PubMed2000

Blockade of voltage-sensitive Ca(2+)-channels markedly diminishes nitric oxide- but not L-S-nitrosocysteine- or endothelium-dependent vasodilation in vivo.

The aim of this study was to determine the hemodynamic responses elicited by systemic injections of (i) the nitric oxide (NO)-donors, sodium nitroprusside (10 nmol/kg, i.v.) and (Z)-1-(N-methyl-N-(6(N-methylammoniohexyl)amino))diazen-1-ium-1, 2-diolate (MAHMA NONOate, 25 nmol/kg, i.v.), (ii) the endothelium-derived S-nitrosothiol, L-S-nitrosocysteine (100 nmol/kg, i.v.), and (iii) the endothelium-dependent agonist, acetylcholine (1.0 microg/kg, i.v.), in anesthetized rats, before and after injection of the voltage-sensitive Ca(2+)-channel (Ca(VS)(2+)-channel) blocker, nifedipine (500 nmol/kg, i.v.). Before injection of nifedipine, the agents produced similar falls in mean arterial blood pressure, and in hindquarter and mesenteric vascular resistances. The depressor and vasodilator responses elicited by sodium nitroprusside and MAHMA NONOate were markedly attenuated by nifedipine. The falls in mean arterial blood pressure and mesenteric resistance elicited by L-S-nitrosocysteine and acetylcholine were not attenuated but the falls in hindquarter resistance were slightly attenuated by nifedipine. The cyclooxygenase inhibitor, indomethacin (10 mg/kg, i.v.), did not affect the actions of sodium nitroprusside, MAHMA NONOate, L-S-nitrosocysteine or acetylcholine or the effects of nifedipine on the hemodynamic actions of these compounds. The decomposition of sodium nitroprusside (0.2 nmol/ml), MAHMA NONOate (0.5 nmol/ml) and L-S-nitrosocysteine (2 nmol/ml) to NO upon addition to rat blood was not affected by nifedipine (10 microM). These findings suggest that (i) exogenously applied NO relaxes resistance arteries in vivo by inhibition of Ca(VS)(2+)-channels whereas L-S-nitrosocysteine and the non-prostanoid endothelium-derived relaxing factor (EDRF) released by acetylcholine acts by additional mechanisms, and (ii) this EDRF may be an S-nitrosothiol which acts independently of its decomposition to NO.

Acetylcholine↗
PubMed2000

Redox regulation of S-nitrosocysteine-mediated vasodilation in vivo.

This study examined the effects of the lipophobic electron acceptor, nitroblue tetrazolium (2x5 micromol/kg, i.v.) on the vasodilation produced by the putative endothelium-derived S-nitrosothiol, L-S-nitrosocysteine (400 nmol/kg, i.v.), and the nitric oxide (NO) donor, (Z)-1-N-methyl-N-[6(N-methylammoniohexyl)amino]&z. sfnc;diazen-1-ium-1,2-diolate (MAHMA NONOate, 25 nmol/kg, i.v.), in anesthetized rats. The administration of nitroblue tetrazolium resulted in delayed but long-lasting increases in vascular resistances. The L-S-nitrosocysteine-induced vasodilator responses were markedly diminished whereas the MAHMA NONOate-induced responses were not affected by nitroblue tetrazolium. These results support the possibility that L-S-nitrosocysteine interacts with membrane thiols that are subject to nitroblue tetrazolium-induced oxidation (i.e., disulfide-bridge formation) and that nitroblue tetrazolium-induced vasoconstriction may involve a loss of potency of endothelium-derived S-nitrosothiols.

Animals↗
PubMed2000

Apparent association of MK-801-sensitive ion channels with L-S-nitrosocysteine recognition sites in the hindlimb vasculature of the rat.

This study demonstrates that the decreases in hindquarter vascular resistance produced by the putative endothelium-derived S-nitrosothiol, L-S-nitrosocysteine, in urethane-anesthetized rats, were attenuated by a lower dose of the N-methyl-D-aspartate (NMDA) receptor ion-channel blocker, dizocilpine (MK-801, 200 microg/kg, i.v.), whereas they were augmented by a higher dose of dizocilpine (500 microg/kg, i.v.). In contrast, L-S-nitrosocysteine-induced decreases in mesenteric vascular resistance were not affected by either dose of dizocilpine. The vasodilator actions of L-S-nitrosocysteine in these beds were not affected by the competitive NMDA receptor antagonist, 2-amino-5-phosphonovaleric acid (2-AP5). The vasodilator actions of the nitric oxide (NO) donor, (Z)-1-mid R:N-methyl-N-[6(N-methylammoniohexyl)amino]mid R:diazen-1-ium-1,2-diolate (MAHMA NONOate), in these beds were not affected by dizocilpine or by 2-AP5. These findings suggest that L-S-nitrosocysteine recognition sites in hindquarter but not mesenteric beds may be associated with dizocilpine-sensitive ion-channels similar to those in NMDA receptors.

2-Amino-5-phosphonovalerate↗
PubMed2000

Functional evidence for the rapid desensitization of 5-HT(3) receptors on vagal afferents mediating the Bezold-Jarisch reflex.

The aim of this study was to determine whether 5-hydroxytryptamine (5-HT)(3) receptors on cardiopulmonary afferents mediating the Bezold-Jarisch reflex (BJR) desensitize upon repeated exposure to selective agonists. BJR-mediated falls in heart rate, diastolic arterial blood pressure and cardiac output elicited by the 5-HT(3)-receptor agonists, phenylbiguanide (100 microg/kg, i.v.) or 2-methyl-5-HT (100 microg/kg, i.v.), progressively diminished upon repeated injection in conscious rats. The BJR responses elicited by 5-HT (40 microg/kg, i.v.) were markedly reduced in rats which had received the above injections of phenylbiguanide or 2-methyl-5-HT whereas the BJR responses elicited by L-S-nitrosocysteine (10 micromol/kg, i.v.) were similar before and after the injections of the 5-HT(3) receptor agonists. These findings suggest that tachyphylaxis to 5-HT(3) receptor agonists may be due to the desensitization of 5-HT(3) receptors on cardiopulmonary afferents rather than the impairment of the central or peripheral processing of the BJR.

Animals↗
PubMed2000

Role of Cl(-) channels in alpha-adrenoceptor-mediated vasoconstriction in the anesthetized rat.

In vitro studies have provided evidence that Cl(-) ion currents are important for activation of vascular smooth muscle contraction. The stilbene, 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS), disrupts Cl(-) metabolism by blocking Cl(-) channels and by inhibiting Cl(-) bicarbonate exchange. The aims of this study were to: (i) characterize the hemodynamic responses produced by DIDS in pentobarbital anesthetized rats, and (ii) examine vasoconstrictor responses to norepinephrine before and after administration of DIDS. DIDS (2.5-50 micromol/kg, 92.5 micromol/kg total dose, i.v.) produced dose-dependent but transient reductions in mean arterial blood pressure and in hindquarter, renal and mesenteric vascular resistances. Prior to the administration of DIDS, norepinephrine (1. 0-5.0 microgram/kg, i.v.) produced dose-dependent increases in mean arterial pressure, renal resistance and mesenteric resistance, but decreases in hindquarter resistance that were inversely related to dose. After administration of DIDS, the peak pressor responses produced by norepinephrine were either slightly diminished (1.0, 2.5 microgram/kg) or unchanged (5.0 microgram/kg). Peak norepinephrine-induced changes in hindquarter and renal vascular resistance were unaffected by DIDS, while increases in mesenteric resistance were augmented. The total norepinephrine-induced increases in mean arterial pressure (mm Hgxs) were markedly reduced by DIDS. These effects of DIDS on norepinephrine-induced responses were similar, but not identical to those of the voltage-sensitive Ca(2+) channel blocker, nifedipine (500 nmol/kg, i.v.). These findings suggest that DIDS may interfere with norepinephrine-induced depolarization of resistance arteries, thereby preventing activation of voltage-sensitive Ca(2+) channels.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed2000

Medial prefrontal cortex acetylcholine injection-induced hypotension: the role of hindlimb vasodilation.

The injection of acetylcholine (ACh) into the cingulate region of the medial prefrontal cortex (MPFC) causes a marked fall in arterial blood pressure which is not accompanied by changes in heart rate. The purpose of the present study was to investigate the hemodynamic basis for this stimulus-induced hypotension in Sprague-Dawley rats. The study was designed to determine whether a change in the vascular resistance of hindlimb, renal or mesenteric vascular beds contributes to the fall in arterial pressure in response to ACh injection into the cingulate cortex. Miniature pulsed-Doppler flow probes were used to measure changes in regional blood flow and vascular resistance. The results indicated that the hypotensive response was largely due to a consistent and marked vasodilation in the hindlimb vascular bed. On this basis, an additional experiment was then undertaken to determine the mechanisms that contribute to hindlimb vasodilation. The effect of interrupting the autonomic innervation of one leg on the hindlimb vasodilator response was tested. Unilateral transection of the lumbar sympathetic chain attenuated the cingulate ACh-induced vasodilation in the ipsilateral, but not in the contralateral hindlimb. These results suggest that the hypotensive response to cingulate cortex-ACh injection is caused by skeletal muscle vasodilation mediated by a sympathetic chain-related vasodilator system.

Acetylcholine↗
PubMed2000

Undetectable serum caeruloplasmin in a woman with chronic hepatitis C infection.

There are many causes of a low serum caeruloplasmin. Not only may this be a feature of Wilson's disease, but a low level may be found in association with chronic liver disease of any cause. We report here a case where undetectable serum caeruloplasmin was found during routine investigation of a woman with hepatitis C viral infection.

Ceruloplasmin↗
PubMed2000

Re-evaluation of normative electronystagmography data in healthy ageing.

Previous work by our group questions the validity of existing electronystagmography (ENG) reference ranges in the elderly. We aim to establish valid reference ranges for ENG in people over 65 on the Nicolet Nystar Plus system. Ninety-six healthy asymptomatic subjects over 65 underwent ENG, including spontaneous and positional nystagmus, saccades, smooth pursuit, optokinetic nystagmus and bithermal calorics; 95% reference ranges with confidence intervals were calculated. The newly determined reference ranges were far wider than those provided by the ENG equipment manufacturer for eight out of 11 parameters (all P < 0.001). Vestibular function is known to deteriorate and become more variable with age. The failure to reflect this change in currently used reference ranges may have contributed to the high rates of vestibular disease reported in some series of dizzy elderly patients. Clinical interpretation of ENG depends on valid reference ranges.

Aged↗
PubMed2000

Vascular reactivity and baroreflex function during hyperthermia in conscious rats.

The hemodynamic responses to vasoconstrictor agents are blunted during heating in anesthetized rats. It is unknown whether reflex neural responses to these agents are also altered during hyperthermia. Therefore, the purpose of this study was to determine the effect of hyperthermia on the hemodynamic and baroreflex-mediated sympathetic neural responses to vasoactive agents in conscious, unrestrained rats. The splanchnic sympathetic nerve activity (SpNA) and systemic and regional hemodynamic responses to injections of phenylephrine and sodium nitroprusside were measured during normothermia (37 degrees C) and hyperthermia (41.5 degrees C). The hemodynamic responses to phenylephrine and sodium nitroprusside were blunted with heating, whereas the SpNA responses to both agents were augmented or unchanged. At 41.5 degrees C, the baroreflex curves relating heart rate (HR) and SpNA to mean arterial blood pressure were shifted to the right. The operating range and gain of the blood pressure (BP)-HR reflex were significantly reduced during heating, whereas the operating range of the BP-SpNA reflex was augmented at 41.5 degrees C. These results indicate that heating alters the cardiovascular and sympathetic neural responses to vasoactive agents in vivo. Furthermore, the data suggest that heating differentially affects arterial baroreflex control of HR and SpNA, shifting both curves toward higher BP values but selectively attenuating baroreflex control of HR.

Animals↗