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Review article: Practical management issues for the Helicobacter pylori-infected patient at risk of gastric cancer.

The public health implications of H. pylori infection are considerable in view of the universality of the infection and its attributable risk in cancer causation. Education of the population as to hygiene and nutrition are prerequisites. Total testing/screening and treatment of the infected population, although cost-effective, appears impractical given the current costs of effective antimicrobial treatment, difficulties with compliance, possibilities of side-effects and especially induction of resistance, and the potential for re-infection. A useful vaccine, probably the best hope, is years away from clinical applicability. Current recommendations focus on a selective test and treatment approach which concentrates on asymptomatic individuals at enhanced risk (gastric cancer families; recognized premalignant lesions such as atrophy, intestinal metaplasia, dysplasia, adenomatous polyps); (hypo)achlorhydria, spontaneous or drug-induced; immunodeficiency; ethnic groups; individual demand and wishes. Clinicians will need to establish their individual set of guidelines regarding 'test and treat' of asymptomatic individuals until the outcome of desperately needed clinical trials becomes available.

Cost-Benefit Analysis↗

Review article: practical management of inflammatory bowel disease patients taking immunomodulators.

Azathioprine, mercaptopurine, methotrexate, ciclosporin and tacrolimus all have their respective niches in the treatment of inflammatory bowel disease. These immunomodulators are potent and effective medications; however, they potentially have serious toxicity. To maximize benefit and minimize risk, clinicians must understand the mechanism of action, appropriate indications, range of toxicity and proper dosing of these medications. Furthermore, once initiating therapy, patients need to be monitored appropriately for evidence of efficacy and toxicity. This review includes the rationale behind recommendations for the management and monitoring of patients using immunomodulators. For the purine antagonists--azathioprine and mercaptopurine--the evidence for utility of thiopurine methyltransferase testing and mercaptopurine metabolite monitoring is addressed. The roles of liver biopsy and screening for methylenetetrahydrofolate reductase mutations in patients taking methotrexate are reviewed. With appropriate monitoring, the calcineurin inhibitors--ciclosporin and tacrolimus--can be used safely and effectively. Immunomodulators are important agents for the treatment of Crohn's disease and ulcerative colitis, and prescribing clinicians should be comfortable recognizing both their value and their limitations.

Dose-Response Relationship, Drug↗

Toxic epidermal necrolysis: current evidence, practical management and future directions.

Toxic epidermal necrolysis (TEN) is a rare disorder characterized by extensive epidermal death. Almost all cases appear to be caused by an idiosyncratic drug reaction. Proposed pathogenic mechanisms are conflicting, and the evidence for the benefits of individual treatments is inadequate, and in some cases contradictory. The mortality rate remains high. We review the literature pertaining to the pathogenesis of TEN and drug reactions in general. The rationale for therapeutic interventions, together with reported evidence of efficacy, are considered. We present a composite model of TEN, based on previous work and suggested pathogeneses of TEN, mechanisms of drug reactions and reported cytotoxic lymphocyte (CTL) cytolytic pathways. In this system, TEN, like some other cutaneous drug eruptions, is an HLA class I-restricted, specific drug sensitivity, resulting in clonal expansion of CD8+ CTLs. Cytotoxicity is mediated by CTL granzyme and possibly death receptor (DR) ligand (DR-L), probably Fas ligand (FasL). Particular to TEN, there is then an amplification sequence involving further DR-L expression. FasL is likely to be particularly important but tumour necrosis factor (TNF) may well contribute, via the TNF receptor 1 (TNF-R1) death pathway. Alternatively, we suggest the possibility of upregulation of an antiapoptotic TNF-R1-nuclear factor kappaB pathway, which would proscribe treatments which downregulate this pathway. None of the published data on individual treatment efficacies is sufficiently strong to suggest a definitive single treatment. Currently a multifaceted regimen appears indicated, targeting various likely intermediary mechanisms, including elimination of residual drug, immunosuppression, inhibition of DR pathways, general antiapoptotic strategies, and aggressive supportive care. Particular attention has been directed at avoiding potential conflicts between different treatments and avoiding agents that theoretically might have a net proapoptotic rather than antiapoptotic effect. Nursing on a specialized unit is of paramount importance.

Adrenal Cortex Hormones↗

A survey of paediatric management practices in Down's syndrome.

Paediatricians throughout Australia and New Zealand completed a questionnaire in which they indicated the type of advice they normally give to parents of children with Down's syndrome. Results indicated strong support for early intervention, discussion with other parents of children with Down's syndrome, and conventional therapy services. Cosmetic surgery appears to be receiving increasing support. Megavitamin therapy, cell therapy and the Doman programme are unsupported. A tendency was noted for paediatricians to underestimate the developmental potential of children with Down's syndrome.

Child↗

Practical management of diabetic ketoacidosis and hyperosmolar coma.

In diabetic ketoacidosis (DKA) and particularly in hyperosmolar coma, rapid normalisation of the measured extracellular fluid abnormalities cannot be equated with optimal management. In both disorders there are complex imbalances between extra- and intracellular compartments that are best corrected in a series of rational steps, based on an understanding of pathophysiology. Fluid administration in DKA can generally be divided into three successive phases: (i) a short period of rapid isotonic saline infusion, (ii) slower infusion of isotonic saline with potassium chloride, and (iii) glucose-potassium infusion until oral food intake is well established. In severe cases, there is a definite place for judicious use of isotonic sodium bicarbonate in small amounts. While insulin infusion is desirable, intramuscular insulin remains a satisfactory alternative. Biochemical monitoring is mandatory and management must be reviewed and modified every three to four hours on the basis of the clinical and biochemical response. In the management of hyperosmolar coma, insulin and fluid therapy are more conservative, with the aim of achieving complete rehydration and normoglycaemia only after 36 to 72 hours. Pulmonary complications and the effects of tissue ischaemia, as well as thromboembolic events, remain important causes of death in both disorders. The frequent recurrences of DKA that occur in a group of psychiatrically-unstable young patients remain an unsolved problem.

Diabetic Coma↗

Advanced heart failure: a practical management algorithm and therapeutic options.

Despite medical and surgical advances in the management of heart failure, 3%-10% of patients clinically reside in the severe stages of this condition. The management of advanced, end-stage heart failure is one of the major challenges of medicine today. An algorithm applicable to the management of severe heart failure is presented and discussed, with an emphasis on medical treatment and therapeutic options.

Adrenergic beta-Antagonists↗

Lithium therapy: from clinical trials to practical management.

Controlled trials have shown that lithium significantly reduces the morbidity of recurrent affective disorders. We describe here the ongoing affective morbidity in unipolar, bipolar and schizoaffective illness treated primarily by low dosage, once daily lithium, supplemented as necessary by antidepressant or neuroleptic medication. Seventy-eight percent of unipolar patients and 73% of bipolar and schizoaffective patients had no or only slight morbidity during the study year. The treatment was equally effective for both older (age greater than 70 years) and younger patients. Unipolar patients rated as endogenous on the Newcastle Scale had significantly lower morbidity than the nonendogenous patients. Subjective side effects were minimal. These patients, whose untreated morbidity is known to be high, derive considerable benefit from regular supervision in an affective disorder clinic.

Adult↗

Practical management of diabetic ketoacidosis in childhood and adolescence.

Diabetic ketoacidosis results from insulin deficiency and insulin resistance and is marked by hyperglycaemia, ketoacidosis, dehydration and electrolyte losses. Management includes correction of shock, dehydration, electrolyte deficits, hyperglycaemia, acidosis and sepsis (if present). Warning signs include severe dehydration, shock, pH < 7.0, hypokalaemia, hypernatraemia, hyperosmolality, hyperlipidaemia, deterioration in consciousness and diabetic ketoacidosis in very young patients. The principles of treatment include (i) admission to a unit with paediatric experience, (ii) treatment of shock, (iii) rehydration over 24-36 h, or longer if the osmolality is >360 mmoll(-1), (iv) normal saline for rehydration unless the patient is hypernatraemic, (v) avoidance of bicarbonate unless acidosis is interfering with myocardial contractility, (vi) insulin infusion to achieve a fall in blood glucose levels of 5 mmol h(-1), (vi) potassium, (vii) use of 5% glucose when the blood glucose level falls <12mmoll(-1), (ix) treatment of any complications and (x) change to subcutaneous insulin when diabetic ketoacidosis is controlled.

Adolescent↗

Leaching of Escherichia coli O157:H7 in diverse soils under various agricultural management practices.

Application of animal manures to soil as crop fertilizers is an important means for recycling the nitrogen and phosphorus which the manures contain. Animal manures also contain bacteria, including many types of pathogens. Manure pathogen levels depend on the source animal, the animal's state of health, and how the manure was stored or treated before use. Rainfall may result in pathogen spread into soil by runoff from stored or unincorporated manure or by leaching through the soil profile. Steady rainfall consisting of 16.5 mm h(-1) was applied to 100-mm disturbed soil cores that were treated with manure and inoculated with Escherichia coli O157:H7 strain B6914. The level of B6914 in leachate was near the inoculum level each hour for 8 h, as was the level of B6914 at several soil depths after 24 h, indicating that there was a high rate of growth. Bacterial movement through three different types of soil was then compared by using disturbed (tilled) and intact (no-till) soil cores and less intense rainfall consisting of 25.4 mm on 4 consecutive days and then four more times over a 17-day period. Total B6914 levels exceeded the inoculum levels for all treatments except intact clay loam cores. B6914 levels in daily leachate samples decreased sharply with time, although the levels were more constant when intact sandy loam cores were used. The presence of manure often increased total B6914 leachate and soil levels in intact cores but had the opposite effect on disturbed soil cores. Ammonia and nitrate levels correlated with B6914 and total coliform levels in leachate. We concluded that tillage practice, soil type, and method of pathogen delivery affect but do not prevent vertical E. coli O157:H7 and coliform transport in soil and that soluble nitrogen may enhance transport.

Agriculture↗