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Biomedical subjects

M J Lewis

Publications and source records attributed to M J Lewis.

At least 217 records · Page 12Linked to original sources
PubMed1988

A randomized cross-over study of enalapril in congestive heart failure: haemodynamic and hormonal effects during rest and exercise.

We performed a randomized double-blind placebo controlled cross-over study of enalapril in 16 patients with chronic congestive heart failure, to assess haemodynamic and hormonal effects at rest and on exercise. Acute effects were measured 4 h after enalapril 10 mg, and chronic effects after 6 weeks treatment with enalapril 10-20 mg per day. Exercise tolerance, assessed by the duration of a maximal bicycle ergometer test, was not altered by enalapril. Mean blood pressure was reduced after enalapril, at rest and on exercise, acutely by 7% and 8% respectively, and chronically by 14% and 16%. Systemic vascular resistance was reduced by 16% at rest both acutely (NS) and chronically (p less than 0.05). The resting pulmonary capillary wedge pressure was reduced by 28% with chronic treatment. In the acute study, total body oxygen consumption on exercise was 26% higher after enalapril. Chronically, resting oxygen consumption was reduced by 13% after enalapril, with mixed venous oxygen saturation increasing by 16%. In the acute study enalapril increased plasma renin activity at rest and on exercise by 181% and by 189%, and reduced aldosterone by 49% (NS) and 39% (p less than 0.05), and these effects were sustained after 6 weeks. Enalapril increased antidiuretic hormone concentrations at rest acutely by 73% (NS) and chronically by 34% (p less than 0.05) but not on exercise; the increase in the acute study correlated with plasma enalaprilat levels (r = 0.66, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

A possible drug interaction between rifampicin and enalapril.

When a 35-year-old man with essential hypertension was treated with antibiotics for brucellosis his blood pressure rose significantly. While all other treatment was kept constant rifampicin was discontinued. On rechallenge rifampicin did not alter serum concentrations of enalapril or the area under the curve (AUC) between 0 and 7 h, but it did reduce the AUC of the active metabolite enalaprilat by 31%. These observations suggest that there may be an interaction between rifampicin and enalapril, causing reduced hypotensive efficacy of enalapril. The mechanism of such an interaction merits further study, but it could be due to enhanced renal clearance of enalaprilat.

Adult↗
PubMed1988

Gross hematuria as a manifestation of infectious mononucleosis.

Gross hematuria is an uncommon manifestation of infectious mononucleosis. This report describes a 19-year-old male with infectious mononucleosis who developed gross hematuria. Infectious mononucleosis should be considered in the differential diagnosis of adolescents with hematuria.

Adult↗
PubMed1988

Endothelium-derived relaxing factor.

This article reviews what is known of endothelium-derived relaxing factor and its possible physiologic and pathophysiologic roles. This relaxing factor is now thought to be nitric oxide or a ready source of it. It acts as an endogenous nitrovasodilator, stimulating soluble guanylate cyclase to increase cyclic guanosine monophosphate (GMP) levels in vascular smooth muscle and platelets, with consequent relaxant and anti-aggregatory effects (predominantly when stimulated through receptor-operated channels). Its actions are thus synergistic with those of cyclic adenosine monophosphate (AMP)-mediated stimulation (for example, adenosine, prostacyclin). Endothelium-derived relaxing factor is unstable and is thought to act only very locally in vivo. Its release is continuous in the basal state and is stimulated by a number of neuropeptides and by agents released during platelet activation and thrombosis--with large differences in activity among different vessels. Endothelium-derived relaxing factor activity is also flow related, thereby coordinating vasomotor behavior in an intact vascular tree in response to changes in flow. Endothelium-derived relaxing factor activity is reduced in several pathologic states, including atherosclerosis.

Animals↗
PubMed1988

Release of endothelium-derived relaxing factor is inhibited by 8-bromo-cyclic guanosine monophosphate.

Endothelial cells are known to contain both soluble and particulate guanylate cyclase, but the functional role of cyclic guanosine monophosphate (cGMP) in endothelial cells remains unknown. We have investigated the effects of 8-bromo-cGMP on endothelium-dependent relaxations to acetylcholine, substance P, ATP, and the calcium ionophore A23187, and on endothelium-independent relaxations to sodium nitroprusside and glyceryl trinitrate (GTN). The ability of each of these agents to relax phenylephrine-preconstricted rings of rabbit aorta was tested in the absence and presence of 8-bromo-cGMP. In the presence of 8-bromo-cGMP, a greater concentration of phenylephrine had to be used to produce a similar level of tone and then endothelium-dependent relaxations to acetylcholine and substance P were inhibited, whereas endothelium-dependent relaxations to ATP and A23187 were unaffected. Endothelium-independent relaxations to sodium nitroprusside and GTN were only inhibited at the highest concentrations of nitroprusside and GTN. These results suggest that: (a) increasing GMP levels in endothelial cells inhibit agonist-induced release of endothelium-derived relaxing factor (EDRF); (b) a negative feedback mechanism may exist whereby EDRF stimulates soluble guanylate cyclase in endothelial cells to inhibit its own release; and (c) ATP does not induce EDRF release via phosphoinositol hydrolysis.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1988

Evidence that inhibitory factor extracted from bovine retractor penis is nitrite, whose acid-activated derivative is stabilized nitric oxide.

1. Unactivated extracts of bovine retractor penis (BRP) contains 3-7 microM nitrite. Acid-activation of these extracts at pH 2 for 10 min followed by neutralization generates the active form of inhibitory factor (IF; assayed by its vasodilator action on rabbit aorta), and is associated with partial loss of nitrite. 2. Increasing the time of acid-activation at pH 2 from 10 to 60 min with intermittent vortex mixing generates greater vasodilator activity and increases nitrite loss. 3. When acid-activated and neutralized extracts are incubated at 37 degrees C or 30 min or boiled for 5 min, vasodilator activity is lost and nitrite content increased. Reactivation of these samples at pH 2 for 10 min followed by neutralization leads to partial recoveries of vasodilator activity with loss in nitrite content. 4. Addition of sodium nitrite to BRP extracts increases acid-activatable vasodilator activity pro rata. 5. Acid-activation of aqueous sodium nitrite solutions results in less loss of nitrite and generation of less vasodilator activity than BRP extracts. Vasodilatation is only transient and is rapidly abolished on neutralization, whereas responses to acid-activated BRP extracts are more prolonged and activity is stable on ice. 6. Bovine aortic endothelial cells yield vasodilator activity that is indistinguishable from that isolated from BRP. It is activated by acid, stable on ice, abolished by boiling or by haemoglobin, and appears to be due to the generation of nitric oxide (NO) from nitrite. 7. The data provide confirmatory evidence that nitrite in BRP extracts is IF, that acid-activation of BRP extracts yields NO which is responsible for its vasodilator action, and that inactivation occurs by decay of NO to nitrite and nitrate. They further suggest that BRP extracts contain a NO-stabilizing agent which favours conversion of nitrite to NO. 8. The finding that bovine aortic endothelial cells yield an agent indistinguishable from IF suggests that nitrite in endothelial cells may likewise be the precursor of endothelium-derived relaxing factor (EDRF), itself identified as NO.

Animals↗
PubMed1988

In vivo EDRF activity influences platelet function.

The administration of carbachol to rabbits to stimulate the release of endothelium derived relaxing factor (EDRF) results in inhibition of platelet aggregation and elevation of platelet cyclic GMP content. These effects are reversed by simultaneous administration of the EDRF inhibitors methylene blue or haemoglobin. The data provide the first direct biochemical evidence of in vivo EDRF activity.

Animals↗
PubMed1988

Vascular smooth muscle sensitivity to endothelium-derived relaxing factor is different in different arteries.

1. The relaxation responses of pre-constricted pig coronary artery (PCA) and rabbit aorta (RA) without endothelium, to endothelium-derived relaxing factor (EDRF) released from either a PCA or RA with intact endothelium have been studied by use of a bioassay cascade system. Effects of EDRF have been compared with sodium nitroprusside (NaNP) and 8-bromo-cyclic GMP. 2. The time course of changes in cyclic GMP levels in response to EDRF in PCA and RA have also been studied. 3. EDRF (released from a PCA or RA) caused significantly greater relaxation in the PCA than the RA, whether 5-hydroxytryptamine or high extracellular potassium was used as the constrictor agonist. 4. These differences in sensitivity to EDRF were paralleled by NaNP but not 8-bromo-cyclic GMP. 5. Cyclic GMP levels peaked earlier in the RA (30s) than in the PCA (180s) but the peak levels were significantly greater in the PCA (2.45 fold) than the RA (1.48 fold). 6. These data show that the previously described differences in EDRF activity between different artery types can be explained in part by differences in the responsiveness of the smooth muscle to EDRF.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1988

Brain stimulation reward: effects of ethanol.

This paper briefly describes and compares the effects of ethanol with those of other abuse substances on brain stimulation reward. The most frequently observed effects of abuse substances on this phenomenon is an increase in sensitivity of the animal to the stimulation. This increased sensitivity to rewarding brain stimulation has been studied as a model of drug-induced euphoria. Although many studies have reported that ethanol does increase the sensitivity of animals to this stimulation, there is much less consistency in results between laboratories than observed with the abused opiates or psychomotor stimulants. Data is presented that suggests that associative factors, e.g., self- versus experimenter-administered ethanol, as well as route of administration and time of brain stimulation testing may all contribute to the variability in results obtained between laboratories. Further, the effects of ethanol on brain stimulation reward are more like those of other sedative-hypnotics than the opiates or psychomotor stimulants.

Alcohol Drinking↗
PubMed1988

Endothelium-derived relaxing factor and nitroprusside compared in noradrenaline- and K+-contracted rabbit and rat aortae.

1. The effects of endothelium-derived relaxing factor (EDRF) (as stimulated by acetylcholine in the presence of endothelium), sodium nitroprusside and 8-bromocyclic GMP on mechanical relaxation, calcium (45Ca) influx and cyclic GMP levels were studied in isolated rabbit aortic preparations pre-contracted either by noradrenaline or by high (120 mM) extracellular potassium. 2. The results confirmed a relatively greater effect of these three interventions on mechanical relaxation and on reducing calcium influx in noradrenaline-contracted than in potassium-contracted preparations. 3. The increase in cyclic GMP levels induced by sodium nitroprusside, contrary to previous reports, was no greater in noradrenaline-stimulated preparations than in potassium-stimulated preparations, a finding confirmed in rat aortic preparations, and relaxation was not associated with a significant reduction of calcium influx in the potassium-stimulated preparations. 4. Cyclic GMP-mediated relaxation of potassium contraction thus appears to be due to actions of cyclic GMP other than on calcium influx. 5. These findings suggest that cyclic GMP reduces calcium influx more through receptor-operated channels than through voltage-operated channels. 6. The endothelium-dependent acetylcholine-induced elevation of cyclic GMP was reduced both by noradrenaline and by high extracellular potassium, possibly by altering release or activity of EDRF. 7. The sensitivity of the soluble guanylate cyclase system to stimulation by EDRF and nitrovasodilators appears to be greater in rat than rabbit aortic preparations.

Animals↗
PubMed1987

A phorbol ester inhibits the release of endothelium-derived relaxing factor.

The effect of the phorbol ester phorbol-12,13-dibutyrate (PDB), an activator of protein kinase C, on endothelium-dependent relaxation was studied in noradrenaline-constricted isolated aortic ring preparations of the rabbit. Endothelium-dependent relaxation induced by acetylcholine or substance P was inhibited by PDB (greater than or equal to 10(-7) M). Endothelium-dependent relaxation induced by the calcium ionophore A23187 (7.5 X 10(-8) and 10(-7) M) was unaffected by PDB (to 10(-6) M). The mechanical responses to acetylcholine or sodium nitroprusside in endothelium-denuded rings were not altered by PDB (to 10(-6) M). The results suggest a role for protein kinase C in receptor-mediated EDRF release mechanisms.

Animals↗
PubMed1987

Effect of lipid feeding on endothelium dependent relaxation in rabbit aortic preparations.

The effect of a cholesterol enriched diet on concentration responses to 5-hydroxytryptamine, ergometrine, and acetylcholine and on endothelium dependent relaxation was investigated in rabbit aortic strip preparations. Sensitivity to ergometrine was slightly reduced after both two and 10 weeks of cholesterol feeding. Sensitivity to 5-hydroxytryptamine was slightly reduced after two but not after 10 weeks of cholesterol feeding. Sensitivity to acetylcholine was not altered at two or 10 weeks in the absence of endothelium, but the endothelium dependent lowering of the constrictor concentration-response was almost abolished after 10 weeks of cholesterol feeding. Likewise the endothelium dependent relaxant response of preconstricted preparations to acetylcholine was almost abolished after 10 weeks of cholesterol feeding. Thus this model of hyperlipidaemia leads after 10 weeks to loss of endothelium dependent relaxation.

Acetylcholine↗
PubMed1987

Endothelium-derived relaxing factor inhibits in vitro platelet aggregation.

We studied the effects of endothelium-derived relaxing factor (EDRF), bovine retractor penis muscle inhibitory factor and sodium nitroprusside, three stimulants of guanylate cyclase, on the in vitro aggregation of washed human platelets. Platelet aggregation induced either by collagen or by the thromboxane A2 analogue U46619 was inhibited by all three agents. The anti-aggregatory effect of each agent was inhibited by haemoglobin. The anti-aggregatory effect of EDRF was potentiated by superoxide dismutase. These findings are discussed in relation to a potential role for EDRF in haemostasis.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1987

Experiences with dual protein bound aqueous vitamin B12 absorption test in subjects with low serum vitamin B12 concentrations.

A dual isotope vitamin B12 absorption test in which vitamin B12 is given both in aqueous solution and bound to protein (chicken serum), was evaluated in 26 controls and 68 patients with subnormal serum vitamin B12 concentrations (19 with pernicious anaemia, 13 with iron deficiency, seven after partial gastrectomy, seven with malabsorptive states, five with folate deficiency, four with chronic alcoholism and 13 in whom no cause was apparent). In control patients protein bound absorption decreased with age; isotope excretion was 1.0% or over in those aged under 60 and 0.5% or over in those aged 60 and above. Malabsorption of protein bound vitamin B12 with normal aqueous absorption occurred in five patients with iron deficiency, three with alcoholism, two after partial gastrectomy, two with folate deficiency and in one with a malabsorptive state. In alcoholics abstinence produced an improvement in protein bound absorption. All patients in the group for whom no cause could be found for the subnormal serum vitamin B12 concentration had normal aqueous absorption but four had malabsorption of protein bound vitamin. Although the dual isotope test gave reproducible results and was consistent with the standard Schilling test some anomalies were detected; nine patients had reduced aqueous absorption with normal protein bound absorption. Despite this the dual test may prove useful in determining the importance of a subnormal vitamin B12 concentration where the cause is not clinically apparent. Further development is needed before it can be considered for routine use.

Absorption↗
PubMed1987

Trial of nifedipine for prevention of oesophageal spasm.

We have used a placebo controlled trial to investigate the effect of long-term administration of nifedipine in the prevention of symptomatic episodes of oesophageal spasm. Diary card scoring was used to assess symptoms in 8 patients with oesophageal spasm who were each given nifedipine and placebo for at least 6 weeks. No significant differences in symptoms between the nifedipine and placebo treatment periods were seen.

Adult↗