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Biomedical subjects

M J Lewis

Publications and source records attributed to M J Lewis.

At least 163 records · Page 9Linked to original sources
PubMed1992

The early alcoholism treatment movement in Australia, 1859-1939.

Advancing ideas pioneered in the United States of America, Australian medical reformers and their lay supporters persuaded colonial governments in the late nineteenth century to recognize that alcohol dependence was a treatable disease. In practice, that recognition was only partial. While inebriates legislation was enacted, the state never provided sufficient resources for adequate specialized treatment facilities to be developed. By the 1930s, the first wave of enthusiasm for specific institutional treatment of alcohol dependence had receded, and the treatment movement was in decline. Reasons are suggested for the failure of the movement.

Journal Article↗
PubMed1992

Action potential duration and endocardial modulation of myocardial contraction in the ferret.

OBJECTIVE: Endocardial endothelium releases substances which modulate myocardial contraction. Selective endocardial removal abbreviates contraction by removing a contraction prolonging substance "endocardin". The aim of the study was to investigate whether changes in action potential duration underlie these contractile effects. METHODS: The contractile effects of shortening the action potential were first characterised, using a potassium channel "opener" cromakalim (3 microM). Transmembrane action potentials were then recorded in isolated ferret papillary muscles before and after endocardial removal. RESULTS: Cromakalim-induced action potential abbreviation reduced contractile twitch duration. Endocardial removal itself however did not alter action potential duration. CONCLUSIONS: Endocardial modulation of cardiac contraction does not involve changes in action potential duration.

Action Potentials↗
PubMed1992

Exogenous nitric oxide inhibits in vivo platelet adhesion following balloon angioplasty.

OBJECTIVES: The aim was to investigate the effects of an exogenous source of nitric oxide on in vivo platelet adhesion at the site of endothelial denudation after balloon angioplasty. METHODS: The study group consisted of 12 anaesthetised Large White pigs. Pigs were randomised to receive SIN-1 (3-morpholino-sydnonimine), an exogenous donor of nitric oxide, or placebo before and during balloon induced vessel wall injury. Platelet deposition was quantified using the injection of autologous 111indium labelled platelets. Platelet function was also monitored by the measurement of bleeding time and ex vivo whole blood aggregometry. RESULTS: Superficial vessel wall injury was confirmed histologically and platelet monolayer formation was demonstrated by scanning electron microscopy. Platelet deposition at the site of endothelial denudation was markedly reduced following SIN-1 administration compared to placebo: 1.266(SEM 0.063) v 1.732(0.060) log platelets x 10(5).cm-2, p = 0.001. SIN-1 raised platelet cyclic GMP concentration, from 4.47(2.48) to 6.14(2.44) pg.platelet-1 (p less than 0.01) and prolonged the bleeding time, from 135(5) to 202(6) s (p = 0.001), but had non-significant effects on ex vivo whole blood aggregometry. CONCLUSIONS: Exogenous nitric oxide, through the activation of platelet soluble guanylate cyclase, inhibits platelet adhesion in vivo following balloon angioplasty.

Angioplasty, Balloon↗
PubMed1992

Gibberellin concentration and transport in genetic lines of pea : effects of grafting.

Effects of the Na and Le loci on gibberellin (GA) content and transport in pea (Pisum sativum L.) shoots were studied. GA(1), GA(8), GA(17), GA(19), GA(20), GA(29), GA(44), GA(8) catabolite, and GA(29) catabolite were identified by full-scan gas chromatography-mass spectrometry in extracts of expanding and fully expanded tissues of line C79-338 (Na Le). Quantification of GAs by gas chromatography-single-ion monitoring using deuterated internal standards in lines differing at the Na and Le alleles showed that na reduced the contents of GA(19), GA(20), and GA(29) on average to <3% and of GA(1) and GA(8) to <30% of those in corresponding Na lines. In expanding tissues from Na le lines, GA(1) and GA(8) concentrations were reduced to approximately 10 and 2%, respectively, and GA(29) content increased 2- to 3-fold compared with those in Na Le plants. There was a close correlation between stem length and the concentrations of GA(1) or GA(8) in shoot apices in all six genotypes investigated. In na/Na grafts, internode length and GA(1) concentration of nana scions were normalized, the GA(20) content increased slightly, but GA(19) levels were unaffected. Movement of labeled GAs applied to leaves on Na rootstocks indicated that GA(19) was transported poorly to apices of na scions compared with GA(20) and GA(1). Our evidence suggests that GA(20) is the major transported GA in peas.

Journal Article↗
PubMed1992

Pharmacokinetics and pharmacodynamics of verapamil following sublingual and oral administration to healthy volunteers.

1. The pharmacokinetics and pharmacodynamics of verapamil administered via the oral and sublingual routes were compared in a randomised, two-way cross-over study involving six healthy male volunteers. 2. Administered sublingually, a verapamil 40 mg (Securon) crushed tablet produced a significantly higher peak plasma concentration (P less than 0.05), a greater rate of absorption (P less than 0.05), and greater bioavailability (P less than 0.05) when compared with orally administered verapamil 40 mg (Securon). 3. In comparison with oral dosing, PR intervals were significantly (P less than 0.05) prolonged between 30 and 90 min after sublingual verapamil dosing. 4. Correlations between log plasma verapamil concentration and percentage increase in PR interval were greater after sublingual compared with oral dosing in all volunteers.

Administration, Oral↗
PubMed1992

Ethanol self-administration in deprived rats: effects of Ro15-4513 alone, and in combination with flumazenil (Ro15-1788).

Previous work in our laboratory demonstrated that Ro15-4513, a partial inverse benzodiazepine agonist, decreases self-administration of ethanol (ETOH) in rats maintained on a two-bottle regmine of a saccharin ethanol solution (ES) and water over a 35-day consumption period. The present study extended the consumption period to 60 days and examined the effects of Ro15-4513 (2.5 mg/kg), flumazenil (Ro15-1788) (8.0 mg/kg), and Ro15-4513 in combination with Ro15-1788 on the time course of ETOH self-administration. High initial intake of ES observed during the first 4 weeks declined significantly over subsequent weeks. Ro15-4513 pretreatment, however, resulted in significant reduction of ES, while significantly preventing the "normal" reduction of consumption as was observed under control conditions. The antagonistic actions of Ro15-4513 were blocked/attenuated by the benzodiazepine receptor antagonist, Ro15-1788, independent of whether consumption of the ES was low or high. Both Ro15-4513 and Ro15-1788 affected water intake differentially compared with vehicle-injected controls. The results suggest that GABA-benzodiazepine mechanisms may be important in altering chronic ETOH drinking patterns depending upon experience with ETOH, tolerance, or learning.

Alcohol Drinking↗
PubMed1992

Evidence for involvement of nitric oxide in the non-adrenergic non-cholinergic (NANC) relaxation of human lower oesophageal sphincter muscle strips.

Electrical field stimulation of circular muscle strips from human lower oesophageal sphincter reveals a predominant relaxation response. This relaxation is non-adrenergic non-cholinergic (NANC). The nitric oxide synthesis-blocking agent N omega-nitro-L-arginine (10-100 microM) reduces or abolishes this NANC relaxation, suggesting involvement of nitric oxide in the response.

Adrenergic Fibers↗
PubMed1992

Influence of prepartum antibiotic therapy on intramammary infections in primigravid heifers during early lactation.

Jersey heifers were assigned alternately to three groups: 1) negative control (n = 41), 2) intramammary infusion of 200 mg of sodium cloxacillin (n = 38) at 7 d before expected parturition, and 3) intramammary infusion of 200 mg of cephapirin sodium (n = 36) at 7 d before expected parturition. The percentage of mammary glands infected prior to treatment was 62.2, 50.0, and 70.1 for groups 1, 2, and 3, respectively. The percentage of mammary glands infected during early lactation was 44.5, 8.6, and 2.1 for groups 1, 2, and 3, respectively. Most infections (87.1%) were due to Staphylococcus species other than Staphylococcus aureus. Thirty-six of 460 quarters were infected with major pathogens before treatment, 3 of 22 persisted following antibiotic treatment, and 9 of 14 persisted in the control group. Infusion of sodium cloxacillin resulted in antibiotic residues in 17.4% of samples obtained .5 d postpartum. All samples were negative at 3 and 10 d postpartum. Infusion of cephapirin sodium resulted in antibiotic residues in 84.7, 28.2, and 0% of samples obtained at .5, 3, and 10 d, respectively. Prepartum antibiotic therapy was effective in eliminating many IMI, especially those caused by coagulase-negative staphylococci, but there is the potential for antibiotic residues in milk.

Animals↗
PubMed1992

Cyclic GMP inhibits the inotropic response to alpha 1-adrenoceptors in the papillary muscle of the ferret.

The physiological role of cyclic GMP in the heart remains controversial. In the present study we investigated the interaction between a number of agents known to increase the level of cyclic GMP in the myocardium and alpha 1-adrenergic stimulation in isolated preparations of cardiac papillary muscle in the ferret. Inotropic responses to the cumulative addition of phenylephrine were measured in papillary muscles of the ferret in the absence and presence of 1 microM sodium nitroprusside, 1 microM atrial natriuretic peptide, 0.1 microM substance P (which stimulates the release of nitric oxide from endocardial endothelium) or 1 microM 8-bromo-cyclic GMP. In parallel experiments using similar preparations, alpha 1-induced hydrolysis of phosphatidylinositol was assessed by measuring changes in the levels of inositol 1,4,5-trisphosphate in response to 10 microM phenylephrine in the absence and presence of the same agents that increase the level of cyclic GMP. Phenylephrine (0.001-10 microM) induced a concentration-dependent positive inotropic effect that was significantly inhibited by each of the agents that increase cyclic GMP. Phenylephrine (10 microM) induced an approximately three-fold rise in the level of inositol trisphosphate in the myocardium, which was likewise significantly inhibited by each of the agents that increase cyclic GMP. These data show that agents that increase the level of cyclic GMP in the myocardium inhibit both the positive inotropic and phosphatidylinositol response to alpha 1-stimulation in isolated preparations of papillary muscle in the ferret.(ABSTRACT TRUNCATED AT 250 WORDS)

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1991

A comparison of endothelium-derived relaxing factor activity in the coronary and renal arteries of the pig.

A cascade bioassay system has been used to quantify the basal and receptor-mediated endothelium-derived relaxing factor (EDRF) activity of pig coronary artery and pig renal artery. When exposed to EDRF released from a common donor vessel, pig coronary artery smooth muscle showed a greater sensitivity to EDRF than pig renal artery, and these differences were paralleled by differential responses to sodium nitroprusside. When mounted as donors in the bioassay, and EDRF detected using a common recipient, pig coronary artery and renal artery endothelium showed similar basal EDRF release rates. EDRF release in response to substance P was greater from pig coronary artery donors, but EDRF release in response to bradykinin was greater from pig renal artery donors. The data indicate that differences in EDRF response and EDRF release occur in different vessels, and that certain EDRF-releasing agents may exert regional vasodilator effects.

Animals↗
PubMed1991

Effects of 8-bromo-cyclic GMP on contraction and on inotropic response of ferret cardiac muscle.

The effects of guanosine 3':5'-cyclic monophosphate (cGMP) on cardiac contraction are not established. Using isolated electrically-stimulated ferret papillary muscle at 29 degrees C, 2.0 mM calcium we investigated the effects of 8-Bromo-cGMP on (a) basal contraction for comparison with the effects of reduction in extracellular calcium or of reduction in resting muscle length; (b) contraction of preparations stimulated by isoprenaline, the dihydropyridine calcium agonist Bay K8644 or post-extrasystolic potentiation. 8-Bromo-cGMP (0.1 mM) induced a small significant reduction in isometric twitch tension (TT) (7%), isotonic shortening (PS) (6%) and in twitch duration, but had no effect on maximum unloaded shortening velocity (Vmax) or rate of tension development (+dT/dt). Reduction in muscle length induced a similar immediate effect on contraction. Reduction of extracellular calcium (2.0 mM to 1.25 mM) reduced TT by 24% and PS by 14% as well as Vmax (19%) and +dT/dt (29%), but did not alter twitch duration. Bay K8644 (0.01 to 10 microM) produced increases in TT, +dT/dt, PS and twitch duration each of which was significantly reduced in the presence of 8-Bromo-cGMP (0.1 mM). 8-Bromo-cGMP had no effect on the responses to isoprenaline 1 nM to 100 microM--which increased TT, +dT/dt and PS but markedly reduced twitch duration--nor on post-extrasystolic potentiation which increased TT and +dT/dt but slightly reduced twitch duration. These results show that 8-Bromo-cGMP induces changes similar to the immediate effects of reduction in resting muscle length, and reduces the positive inotropic effects of Bay K8644 but not those of isoprenaline or post-extrasystolic potentiation.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1991

A large outbreak of food poisoning of unknown aetiology associated with Stilton cheese.

Between November 1988 and January 1989, a total of 155 people in 36 reported outbreaks suffered gastrointestinal symptoms associated with eating Stilton cheese, produced from unpasteurized cow's milk in the English midlands. Symptoms were suggestive of a staphylococcal illness but extensive laboratory testing of cheeses implicated in several of the outbreaks failed to detect any pathogen, toxin or chemical. Control measures were implemented, and included a voluntary withdrawal of the implicated Stilton cheese from sale on 23 January 1989 and a subsequent decision to use pasteurized milk in production of the cheese.

Abdominal Pain↗
PubMed1991

Mitozantrone and cytosine arabinoside as first-line therapy in elderly patients with acute myeloid leukaemia.

We have prospectively evaluated a regimen of mitozantrone and cytosine arabinoside (Ara-C) as first-line therapy in elderly patients with acute myeloid leukaemia (AML). One hundred and four patients with a median age of 68 (range 60-81) were studied, in whom 86 had de-novo AML, and 18 had preceding myelodysplasia or secondary AML. Complete remission was achieved in 64% of de-novo cases, in 28% of MDS/secondary cases, and in 58% overall. The incidence of early death within 28 d of chemotherapy was 11%. The median disease-free survival (DFS) was 11 months with an actuarial DFS of 15% at 43 months. The median overall survival was 9 months with an actuarial survival of 10% at 44 months. The incidence of non-haematological toxicity was acceptably low, and usually of mild to moderate severity. Quality of life was improved, or unchanged, in 90% of responders. We conclude that mitozantrone and ara-C is an effective and well-tolerated regimen which produces high remission rates in elderly patients with AML.

Acute Disease↗
PubMed1991

Inhibition of inositol 1,4,5-trisphosphate formation by cyclic GMP in cultured aortic endothelial cells of the pig.

1. In cultured endothelial cells of the pig the endothelium-derived relaxing factor (EDRF) releasing agent thrombin (2 u ml-1) caused a significant increase in basal levels of both guanosine 3':5'-cyclic monophosphate (cyclic GMP) and inositol 1,4,5-trisphosphate (IP3). This increase was time dependent, with peak levels occurring at 2 min and returning towards basal values after 5 min. 2. Pretreatment of the cells with the EDRF inhibitors haemoglobin (1 microM) or L-NG-nitro arginine (50 microM) significantly reduced the cyclic GMP response to thrombin. Both agents also resulted in significant elevations in basal levels of IP3. The IP3 response to thrombin was significantly enhanced at all time points by haemoglobin and at 5 min for L-NG-nitro arginine, when compared with the response to thrombin alone. 3. Pretreatment of the cells with either sodium nitroprusside (10 microM) or atrial natriuretic peptide (1 microM) caused a significant elevation of basal cyclic GMP levels. Although subsequent exposure to thrombin caused a further increase in cyclic GMP, which together with the rise induced by the previous two agents was significantly greater than the increase caused by thrombin alone, the incremental increase induced by thrombin was markedly less in the presence of nitroprusside or atrial natriuretic peptide. Both these agents, as well as 8-bromo cyclic GMP, resulted in a significant suppression of the IP3 response to thrombin. 4. These findings show that one mechanism for the inhibitory effect of cyclic GMP on EDRF release from endothelium may be through the inhibition of IP3 formation in response to EDRF releasing agents.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1991

Nitric oxide synthase in cultured endocardial cells of the pig.

1. Endocardial cells release factors which regulate myocardial contractility and guanosine 3':5'-cyclic monophosphate (cyclic GMP) levels. One of these factors is indistinguishable from endothelium-derived relaxing factor (EDRF). 2. The effluent from pig heart endocardial cells cultured on microcarrier beads caused the relaxation of a pig coronary artery ring denuded of endothelium. This relaxation was enhanced by a combination of superoxide dismutase and catalase and was attenuated by haemoglobin, which binds nitric oxide (NO), and by inhibitors of NO synthase, NG-monomethyl-L-arginine (L-NMMA) or NG-nitro-L-arginine. 3. A Ca(2+)-, L-arginine- and NADPH-dependent enzyme activity which generated NO was detected by a specific spectrophotometric assay in cytosol prepared from endocardial cells. The formation of NO was inhibited in a concentration-dependent manner by L-NMMA (but not D-NMMA) and this could be partially reversed upon addition of excess L-arginine. 4. Like endothelial cells from the blood vessels, the endocardial cells possess the ability to synthesize NO, which may act to regulate myocardial contractility.

Amino Acid Oxidoreductases↗