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Biomedical subjects

John A Henry

Publications and source records attributed to John A Henry.

11 recordsLinked to original sources

Alpha 1-acid glycoprotein reverses cocaine-induced sodium channel blockade in cardiac myocytes.

UNLABELLED: Alpha 1-acid glycoprotein (AAG) is an acute phase protein capable of binding basic drugs. This action explains its reversal of sodium channel blockade by drugs such as amitriptyline and quinidine. We report here the reversal of cocaine-induced sodium channel blockade by AAG. The sodium channel blocking property of cocaine is a major mechanism behind cocaine-induced sudden cardiac death, since sodium channels play a key role in the initiation and regulation of the heart beat. Voltage-gated sodium current (I(Na)) was recorded using whole-cell patch-clamp techniques. Guinea-pig cardiac ventricular myocytes were isolated and continuously perfused at room temperature with physiological solutions. At concentrations ranging from 5 to 320 microM cocaine showed a dose-dependent and reversible blockade of I(Na) with an IC50 of 45.9 microM. The addition of equimolar amounts of AAG to cocaine produced almost complete reversal of cocaine's effects, suggesting a single binding site for cocaine on the AAG molecule. With changes of peak I(Na) normalized against control as 1, cocaine at 20 and 40 microM reduced I(Na) to 0.62+/-0.042 (n = 6) and 0.57+/-0.052 (n = 9), respectively, and the addition of an equimolar concentration of AAG reversed I(Na) to 0.86+/-0.022 and 0.91+/-0.060, respectively. IN CONCLUSION: AAG reverses cocaine-induced sodium channel blockade in a dose-dependent manner, indicating a therapeutic potential to reverse acute cocaine cardiac toxicity.

Animals↗

Cannabis as a precipitant of cardiovascular emergencies.

Cannabis smoking is on the increase both in the United Kingdom and in the United States. For over three decades it has been known that cannabis has pathophysiological effects on the cardiovascular system, and previously an association with an increased risk of myocardial infarction has been reported. However, it is not yet known whether cannabis contributes directly to coronary artery disease. We describe two distinct cases; in the first cannabis use precipitated a malignant arrhythmia in a patient with critical ischaemia from longstanding coronary artery disease. In the second, a young patient presented with an acute myocardial infarction that had started whilst smoking marijuana; subsequently diffuse coronary artery disease was found at angiography despite the patient's low risk factor status. Patients who are known cannabis smokers and who have cardiovascular disease should be warned that it is likely to aggravate coronary ischaemia, and may even trigger myocardial infarction.

Adult↗

Cost-effectiveness of screening and referral to an alcohol health worker in alcohol misusing patients attending an accident and emergency department: a decision-making approach.

We present the cost and cost-effectiveness of referral to an alcohol health worker (AHW) and information only control in alcohol misusing patients. The study was a pragmatic randomised controlled trial conducted from April 2001 to March 2003 in an accident and emergency department (AED) in a general hospital in London, England. A total of 599 adults identified as drinking hazardously according to the Paddington Alcohol Test were randomised to referral to an alcohol health worker who delivered a brief intervention (n = 287) or to an information only control (n = 312). Total societal costs, including health and social services costs, criminal justice costs and productivity losses, and clinical measures of alcohol consumption were measured. Levels of drinking were observably lower in those referred to an AHW at 12 months follow-up and statistically significantly lower at 6 months follow-up. Total costs were not significantly different at either follow-up. Referral to AHWs in an AED produces favourable clinical outcomes and does not generate a significant increase in cost. A decision-making approach revealed that there is at least a 65% probability that referral to an AHW is more cost-effective than the information only control in reducing alcohol consumption among AED attendees with a hazardous level of drinking.

Adult↗

Acute, sub-acute and long-term subjective consequences of 'ecstasy' (MDMA) consumption in 430 regular users.

This study examined the reported psychological effects of different patterns of MDMA use in men and women, and how they are modified by use of other psychoactive substances. A semi-structured interview was conducted with 466 regular MDMA users, exploring the perceived acute, sub-acute and long-term subjective effects of this drug. Factor analysis established three main categories of acute effects of MDMA: (i) positive and (ii) negative effects on mental health, and (iii) physical effects. In terms of subacute effects, 83% of participants reported experiencing low mood and 80% reported impaired concentration between ecstasy-taking sessions. Factors affecting these effects included age, gender, extent of MDMA use and concomitant use of cocaine or amphetamine. The long-term effects most frequently reported included the development of tolerance to MDMA (59%), impaired ability to concentrate (38%), depression (37%) and 'feeling more open towards people' (31%). In terms of what might persuade users to stop using MDMA, their most prominent concern was the drug's long-term effects on mental health.

Adolescent↗

Death following ingestion of MDMA (ecstasy) and moclobemide.

Four deaths following the ingestion of moclobemide and MDMA ('ecstasy') are described. The probable cause of death in each case was serotonin syndrome as a result of an interaction between the two drugs. As none of the victims had been prescribed moclobemide it seems that each had taken the drug to enhance the effects of MDMA, with fatal consequences. Warnings are needed against misinformed attempts to potentiate the pharmacological effects of illicit drugs.

Adolescent↗

Screening and referral for brief intervention of alcohol-misusing patients in an emergency department: a pragmatic randomised controlled trial.

BACKGROUND: Alcohol misuse is highly prevalent among people attending emergency departments, but the effect of intervention by staff working in these departments is unclear. We investigated the effect of screening and referral of patients found to be misusing alcohol while attending an emergency department. METHODS: We undertook a single-blind pragmatic randomised controlled trial. Patients received either an information leaflet or an information leaflet plus an appointment with an alcohol health worker. Outcome data were collected by patient interview and examination of hospital records at 6 and 12 months. FINDINGS: 599 patients were randomised over a 12-month period. At 6 months, those referred to an alcohol health worker were consuming a mean of 59.7 units of alcohol per week compared with 83.1 units in the control group (t -2.4, p=0.02). At 12 months those referred were drinking 57.2 units per week compared with 70.8 in controls (t -1.7, p=0.09). Those referred to the alcohol health worker had a mean of 0.5 fewer visits to the emergency department over the following 12 months (1.2 compared with 1.7, t -2.0, p=0.046). Differences in quality of life were not found. INTERPRETATION: Opportunistic identification and referral for alcohol misuse in an emergency department is feasible, associated with lower levels of alcohol consumption over the following 6 months, and reduces reattendance at the department. Short-term reductions in alcohol consumption associated with referral for brief intervention for alcohol misuse benefit patients and reduce demand for accident and emergency department services.

Adult↗

The Royal College of Physicians report on alcohol: guidelines for managing Wernicke's encephalopathy in the accident and Emergency Department.

The Royal College of Physicians (London) recently published its latest report on alcohol misuse entitled 'Alcohol - Can the NHS Afford It?'. Part of this document, encompassing our views, has made specific recommendations for the management of patients in the Accident and Emergency (A&E) Department who may possibly have, or are at risk of developing, Wernicke's encephalopathy. Patients showing evidence of chronic alcohol misuse and suspected of having a poor diet should be treated at the outset with B vitamins intravenously or intramuscularly, especially when the clinical signs are initially masked by drunkenness at presentation to the A&E Department. This commentary offers a review of the scientific foundations on which these recommendations have been made.

Alcoholism↗