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Biomedical subjects

K L Woods

Publications and source records attributed to K L Woods.

At least 19 recordsLinked to original sources

Intravenous magnesium sulphate in suspected acute myocardial infarction: results of the second Leicester Intravenous Magnesium Intervention Trial (LIMIT-2)

The cardiovascular actions of the magnesium ion at pharmacological concentrations include coronary and systemic vasodilatation, platelet inhibition, and antiarrhythmic effects. Magnesium has also been reported to protect myocardial tissue in experimental models of ischaemia and reperfusion. Several small clinical trials in suspected acute myocardial infarction have suggested that early mortality can be reduced by intravenous infusion of magnesium salts in the acute phase, but none has been of sufficient size to be conclusive. We therefore conducted a randomised, double blind, placebo controlled study in 2316 patients with suspected acute myocardial infarction who received either intravenous magnesium sulphate (8 mmol over 5 min followed by 65 mmol over 24 h) or physiological saline. The primary outcome measure was 28-day mortality, which was ascertained in 99.3% of patients. The groups were well balanced for prognostic factors. By intention-to-treat analysis mortality from all causes was 7.8% in the magnesium group and 10.3% in the placebo group (2p = 0.04), a relative reduction of 24% (95% confidence interval 1-43%). Within the coronary care unit the incidence of left ventricular failure was reduced by 25% (7-39%) in the magnesium group (2p = 0.009). There was no significant difference between the groups in the incidence of heart block or the use of antiarrhythmic drugs, direct-current cardioversion, or temporary pacing. Myocardial infarction was confirmed in 65% of each group, with closely similar rises in cardiac enzymes. The side-effects of magnesium treatment were transient flushing, related to speed of injection of the loading dose, and an increased incidence of sinus bradycardia (2p = 0.02). Exploratory subgroup analyses of 28-day mortality did not indicate any effect modification by thrombolysis or aspirin, or by previous treatment with beta blockers, calcium antagonists, or diuretics. Intravenous magnesium sulphate is a simple, safe, and widely applicable treatment. Its efficacy in reducing early mortality of myocardial infarction is comparable to, but independent of, that of thrombolytic or antiplatelet therapy.

Aged

Cerebrovascular carbon dioxide reactivity and failure of autoregulation in preterm infants.

Changes in cerebral blood flow velocity (CBFV) in response to a rise in arterial carbon dioxide tension (PaCO2) in 94 ventilated preterm infants were determined using Doppler ultrasound to assess whether the nature of this change might predict subsequent neurological injury. Concomitant changes in mean arterial pressure (MAP) were recorded. Both CBFV and MAP rose significantly in response to the rise in PaCO2, the response being significantly less in the first 24 hours. Analysis indicated that the change in CBFV in the first day of life in infants less than or equal to 30 weeks' gestation was dependent to a great extent on the concomitant change in MAP. Similar dependence also occurred after administration of pancuronium to infants whose CBFV response was previously independent of changes in MAP. This dependency lasted for the duration of paralysis. Changes in CBFV after a rise in PaCO2 did not predict subsequent neurological injury. The influence of pancuronium on cerebrovascular regulation warrants further study.

Blood Flow Velocity

Modification of the circadian rhythm of onset of acute myocardial infarction by long-term antianginal treatment.

OBJECTIVE: To elucidate the mechanism of the circadian pattern of onset of acute myocardial infarction by examining the effects of prior antianginal treatment upon it. DESIGN: Retrospective analysis of clock time of the onset of acute myocardial infarction by linear modelling to define the circadian distribution of hourly onset rates and to examine the deviation of treated groups of patients from this distribution. SETTING: Coronary care unit in a general hospital taking unselected acute admissions from a district of 0.9 million people. PATIENTS: A series of 2231 patients with confirmed acute myocardial infarction. RESULTS: A major 24 h cycle and smaller 12 h and 6 h cycles were present in patients not taking antianginal medication. Onset rates varied twofold over the day, with maxima around 10.00 am and 10.00 pm. This pattern was unchanged in patients on prior treatment with regular nitrates, but in those who had been taking a beta blocker or a calcium antagonist the 24 h cycle was absent. CONCLUSIONS: These results are best explained by the shared property of beta blockers and calcium antagonists to reduce blood pressure and myocardial oxygen demand. The mid-morning peak of the onset of myocardial infarction is attributable to the physiological increase in sympathetic drive and cardiac work at that time. The data are not consistent with the triggering of the 24 h periodicity by fluctuations in coronary tone or haemostatic activity.

Adrenergic beta-Antagonists

Intracellular metabolism of the antiherpes agent (S)-1-[3-hydroxy-2-(phosphonylmethoxy)propyl]cytosine.

(S)-1-[3-Hydroxy-2-(phosphonylmethoxy)propyl]cytosine (HPMPC) is an antiviral phosphonate nucleotide analogue that displays activity against a range of herpesviruses. Anion exchange high performance liquid chromatography analysis of the 60% methanol extract from [14C]HPMPC-treated cells reveals the formation of three major metabolites. Two of these were identified as phosphorylated forms of HPMPC, HPMPC phosphate, and HPMPC diphosphate, by liberation of HPMPC upon acid digestion and coelution with synthetic standards on high performance liquid chromatography. The third metabolite, which is resistant to alkaline phosphatase cleavage but sensitive to phosphodiesterase, is proposed to be an HPMPC phosphate adduct. In herpes simplex virus-1-infected cells the same three metabolites are detected, at concentrations comparable to those in uninfected cells. When HPMPC is removed from the medium, the concentrations of the metabolites in cells decrease slowly, with half-lives of approximately 6, 17, and 48 hr for HPMPC phosphate, HPMPC diphosphate, and the HPMPC phosphate adduct, respectively. HPMPC diphosphate inhibits herpes simplex virus-1 and -2 DNA polymerases with a lower Ki than that for DNA polymerase alpha, and enzyme inhibition is competitive in each case. The formation and the persistence of HPMPC phosphates in cells and the selective inhibition of viral DNA polymerases by HPMPC diphosphate can explain why cells pretreated with HPMPC remain refractory to viral infection even long after HPMPC is removed from the medium.

Animals

Bacon's chicken.

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Food Preservation

The effects of flosequinan on regional blood flow in normal man.

1. The effects of 100 mg and 200 mg flosequinan on limb, hepatic and renal blood flow were investigated in 14 healthy male volunteers in a placebo controlled double-blind randomised three-way crossover study. 2. Heart rate, blood pressure, forearm blood flow and venous capacitance measured by volume plethysmography, were recorded sequentially over 4 h, after oral dosing. 3. Apparent hepatic and renal blood flows were estimated 2 h post-dose by indocyanine green dye clearance and clearance of 125-iodohippuran respectively. 4. Flosequinan produced dose-dependent reductions in resting diastolic blood pressure, accompanied by a rise in heart rate. 5. Forearm blood flow increased to a maximum 4 h after 200 mg and this was accompanied by a fall in forearm vascular resistance. 6. Hepatic blood flow increased, compared with placebo, after 200 mg flosequinan, accompanied by a fall in hepatic vascular resistance. Renal blood flow remained unchanged but renal vascular resistance fell significantly, compared with placebo, following both doses of the drug. 7. In normal man blood flow to the limb, hepatic and renal vascular beds is preserved despite dose-dependent reductions in blood pressure following single doses of flosequinan.

Double-Blind Method

The effects of demographic shift on coronary heart disease mortality in a large migrant population at high risk.

Asian immigrants to the United Kingdom and elsewhere are at greater risk of mortality and morbidity from coronary heart disease (CHD) than UK whites. This predisposition has yet to be explained. More than 63,000 Asian people, a high proportion of whom are under 40, live in Leicester. Projections of the local Asian and non-Asian populations indicate that numbers of Asian people in higher-risk age groups will more than double between 1988 and 2008. In the absence of effective intervention, numbers of CHD deaths among Asian people, and the prevalence of other manifestations of CHD in this group, will rise by an equivalent amount. This predicted shift in the ethnic distribution of CHD has important implications for the planning of acute services in Leicester. Our predictions also demonstrate both a valuable opportunity and a pressing need for local research into the aetiology of CHD among Asian people, upon which preventative strategies may be based.

Adult

A new endoscopic method for managing food impaction in the esophagus.

Previously described methods for dealing with acute food impaction in the esophagus are not uniformly efficacious, are cumbersome, and often prove dangerous. This paper describes a new technique using an endoscope which is modified such that the endoscope itself becomes a direct-vision suction device. We have successfully used the technique in seven patients with meat bolus impaction in the esophagus. The method proved quick and safe, and no complications occurred. After relieving the impaction an adequate diagnostic examination was done in all patients. In four patients with a predisposing peptic stricture and one with Schatzki's ring, treatment of the lesion was possible during the same endoscopic session.

Adult

Reappraisal of thyroxine treatment in primary hypothyroidism.

The optimum daily dose of thyroxine was calculated for 13 children aged 3-16 years with primary hypothyroidism by titrating their doses at monthly intervals. The condition of the thyroid was assessed by sensitive assay of thyroid stimulating hormone concentrations, as well as measurement of total and free thyroid hormone concentrations and systolic time interval ratios. Serum thyroid stimulating hormone concentration was found to be the most responsive to small changes in thyroxine. The calculated optimum daily replacement dose of thyroxine (102 micrograms/m2 or 3.5 micrograms/kg) was fractionally lower than that previously recommended, and was more closely related to surface area (coefficient of variation 8.2%) than to body weight (coefficient of variation 16.2%). Our results suggest that though monthly may be the optimal time interval for increases in the dose of thyroxine, any reduction in the dose should be made more gradually.

Adolescent

Circulatory effects of fast ventilator rates in preterm infants.

High frequency positive pressure ventilation has been suggested to result in a lower incidence of respiratory complications in preterm infants with idiopathic respiratory distress syndrome compared with ventilation at conventional rates. A possible disadvantage is compromise of the infant's cardiovascular condition secondary to inadvertent positive end expiratory pressure (PEEP). In a group of 20 such infants treated with high frequency positive pressure ventilation (rates of up to 100/minute) and analysed, changes in arterial blood pressure and cerebral blood flow velocity were largely influenced by changes in arterial blood gases, and no effect could be attributed to inadvertent PEEP. In addition, the observed fall in both arterial carbon dioxide and oxygen tensions could be readily predicted for theoretical reasons. Under certain conditions at the fastest rates used, cerebral blood flow velocity was significantly influenced by changes in blood pressure, which may indicate impaired cerebrovascular regulation. Though other factors (such as the severity of the infants' illness or the use of paralysis) may have been responsible for this apparent blood pressure passivity, the role of high frequency positive pressure ventilation in such infants warrants further study.

Blood Flow Velocity

Accidental self administration of xylazine in a veterinary nurse.

A 19 year old male veterinary nurse accidentally injected himself with 200 mg of xylazine (a muscle relaxant and sedative used in veterinary practice). He subsequently became comatose, hypotensive, bradycardic and acidotic. He required intensive supportive therapy, and made a full recovery over the next few hours. Xylazine toxicity in humans is very rare, and the effects are discussed.

Accidents, Occupational

Effects of calcium channel blockers on in vitro platelet function in whole blood using single platelet counting.

The effects of various calcium channel blockers on in vitro platelet aggregation were studied using whole blood platelet counting. Diltiazem and verapamil inhibited aggregation caused by adrenaline 5 microM and collagen 2 micrograms/ml, but only at concentrations far in excess of those seen in clinical use. Nifedipine and nimodipine also inhibited aggregation to these agonists, but this seemed to be due to the solvent used. The solvent for these dihydropyridines contains 15% ethanol, 15% polyethylene glycol and 70% water, and the ethanol component is the most likely to have caused an antiaggregatory effect. Other studies showing an antiaggregatory effect of dihydropyridines may not have taken account of this solvent effect.

Adult