Evidence for the utilisation of substrates by the ischaemic myocardium and its dependence for viability on a critical supply of glucose was established many years ago. It was recognised that an excess of free fatty acids (FFA) could increase the severity of ischaemic damage and possibly be arrhythmogenic. But metabolic intervention to improve survival during acute myocardial infarction was not regarded as a priority, perhaps because of uncertainty about its value and the advent of trials of beta-blocker and antiarrhythmic drugs. There has never been an adequate trial of the benefit to the ischaemic or infarcting myocardium of increasing local glucose concentrations or reducing the availability of FFA. We have taken into account new knowledge of the effects of fatty acids on cation channels and brought up to date the arguments for metabolic intervention with glucose-insulin solutions or antilipolytic drugs sustained ischaemia.

Nicotine-replacement therapy (NRT) by gum, transdermal patch, intranasal spray, or inhalation is expensive but how effective is it? We have done a meta-analysis of controlled trials to see how effects on abstinence rates are influenced by the clinical setting, the level of nicotine dependency, the dosage of NRT, and the intensity of additional advice and support offered. Published or unpublished randomised controlled trials of NRT that have assessed abstinence at least 6 months after the start of NRT were identified and 53 trials (42 gum, 9 patch, 1 intranasal spray, 1 inhaler), with data from 17,703 subjects, were included in the analyses. Use of NRT increased the odds ratio (OR) of abstinence to 1.71 (95% confidence interval 1.56-1.87) compared with those allocated to the control interventions. The ORs for the different forms of NRT were 1.61 for gum, 2.07 for transdermal patch, 2.92 for nasal spray, and 3.05 for inhaled nicotine. These odds were non-significantly higher in subjects with higher levels of nicotine dependence but they were largely independent of the intensity of additional support provided or the setting in which NRT was offered. We conclude that the currently available forms of NRT are effective therapies to aid smoking cessation.

The recommended approach to the increased risk of colorectal carcinoma in ulcerative colitis has been colonoscopic surveillance rather than prophylactic colectomy. This strategy is based on the assumption that dysplastic lesions can be detected before invasive cancer has developed. We have analysed published reports on dysplasia surveillance to find out whether this assumption is valid. Ten prospective studies (1225 patients) satisfied our criteria. Of 40 patients with dysplasia-associated mass or lesion (DALM) detected, 17 (43%) already had cancer at immediate colectomy. The risks of cancer at immediate colectomy were 42% (10 of 24 patients) for high-grade and 19% (3 of 16) for low-grade dysplasia. Of 47 patients found to have high-grade dysplasia after the initial colonoscopy, 15 (32%) had cancer. 16-29% of patients with untreated low-grade dysplasia progressed to DALM, high-grade dysplasia, or cancer. Of patients with indefinite results, 28% progressed to high-grade dysplasia and 9% to cancer, so continued surveillance is essential. The risk of progression to dysplasia was only 2.4% for patients whose initial result was negative, so surveillance could perhaps be less frequent for these patients. Immediate colectomy is essential for all patients diagnosed with high-grade or low-grade dysplasia. A diagnosis of dysplasia does not preclude the presence of invasive cancer. We believe that patients should be informed about the limitations of colonoscopic surveillance so that they can take part rationally in decision-making about their management.

Any hypothesis on the cause of ulcerative colitis must account for genetic influences, geographic and ethnic variations, effects of smoking and oral contraception, anatomical distribution, the relapsing and remitting nature of the disease, and association with primary sclerosing cholangitis. This hypothesis proposes that ulcerative colitis is caused by a reactive xenobiotic metabolite which is conjugated before excretion into bile. The amount of metabolite produced is determined by exposure to its parent compound, by the inherited pattern of metabolism, and by inhibition and induction of enzymes catalysing alternative pathways. Deconjugation by bacteria within the colonic lumen releases the reactive metabolite, damaging the colonic epithelial barrier and exposing the mucosal immune system to luminal contents. Biliary epithelial damage by the metabolite leads to an immune response in those individuals carrying appropriate HLA molecules, thereby initiating an inflammatory process within the biliary tree.

Although 4000 pancreas transplants have now been done, alone or in combination with a kidney transplant, the risk/benefit profile of the procedure has not been established by controlled studies. A solo pancreas transplant abolishes the need for daily insulin but requires chronic immunosuppression, has high failure rates, and is not proved to lessen the chronic complications of diabetes. Thus, it is probably justified only in those diabetic patients with incapacitating disease. For uraemic diabetic patients, combined pancreas and kidney transplantation often removes dependence on both insulin and dialysis, and has lower rejection rates than pancreas transplant alone. However, it needs more immunosuppression than kidney transplant alone, has no proven benefit on chronic complications of diabetes, and carries an increased risk of rejection, infection, and cancer. Living-related-donor kidney transplantation followed by cadaver pancreas transplantation is a possible alternative. Transplantation of pancreatic islets could offer the advantages of strict metabolic control without the drawbacks of immunosuppressive therapy. Thus, research efforts should concentrate on immune-protected islet transplantation. An alternative approach to avoiding long-term immunosuppression is the promotion of allograft tolerance.

Chinese herbal medicines (CHM) and Chinese proprietary medicines (CPM) are widely used by people of Chinese origin throughout the world. Although the use of these medicinal materials rarely causes significant toxic effects, cases of severe and even fatal poisoning have occurred after medication with herbs containing aconitine, podophyllin, and anticholinergic substances. Furthermore, CHM and CPM are often adulterated with substituted herbs, heavy metals, and western medicines; such contamination can have important clinical consequences. In Hong Kong, surveillance and legislation are required to control the use of some of these herbal preparations. In other countries, medical practitioners should also be aware of the possibility that these herbal-medicine-related remedies may cause significant clinical problems in their Chinese patients.

Although interest in clinical guidelines has never been greater, uncertainty persists about whether they are effective. The debate has been hampered by the lack of a rigorous overview. We have identified 59 published evaluations of clinical guidelines that met defined criteria for scientific rigour; 24 investigated guidelines for specific clinical conditions, 27 studied preventive care, and 8 looked at guidelines for prescribing or for support services. All but 4 of these studies detected significant improvements in the process of care after the introduction of guidelines and all but 2 of the 11 studies that assessed the outcome of care reported significant improvements. We conclude that explicit guidelines do improve clinical practice, when introduced in the context of rigorous evaluations. However, the size of the improvements in performance varied considerably.

There is disagreement on the usefulness of comprehensive geriatric assessment (CGA) due to conflicting results from individual trials. We did a meta-analysis on 28 controlled trials comprising 4959 subjects allocated to one of five CGA types and 4912 controls. Published data were supplemented with reanalysed data provided by the original investigators. We calculated combined odds ratios of important outcomes by pooling data from individual trials with multivariate logistic regression. Combined odds ratio (95% confidence interval) of living at home at follow-up was 1.68 (1.17-2.41) for geriatric evaluation and management units, 1.49 (1.12-1.98) for hospital-home assessment services, and 1.20 (1.05-1.37) for home assessment services. Covariate analysis showed that programmes with control over medical recommendations and extended ambulatory follow-up were more likely to be effective. Our analysis suggests that CGA programmes linking geriatric evaluation with strong long-term management are effective for improving survival and function in older persons.

I propose that fainting (vaso-vagal syncope) is caused by the sudden invagination of the walls of underfilled atria and great veins when their intraluminal pressure no longer exceeds intrathoracic pressure, leading to anomalous collapse-firing of veno-atrial stretch receptors. Impulses therefrom cause reflex systemic vasodilation and bradycardia, probably through a brainstem relay path involving opioids and possibly the A5 area of the medulla. The inappropriate increase of afferent atriovenous baroreceptor-nerve activity leads, by a vicious circle, to a sudden collapse of systemic arterial pressure. Activation of ventricular receptors is neither a probable nor a necessary cause of syncope, though it might be part of the response.