Review article: controversy in the therapy of gastro-oesophageal reflux disease—long-term proton pump inhibition or laparoscopic anti-reflux surgery?

The treatment of gastro-oesophageal reflux disease is controversial. Whilst medical treatment is successful in patients with mild to moderate disease, the threshold of severity above which an operation should be contemplated remains a matter for debate. Laparoscopic anti-reflux surgery may be lowering this threshold, as this form of therapy provides several advantages over its open counterpart, but it is not without risk, and few long-term results are available. This article reviews treatment options for reflux disease and examines the relative position of current medical and surgical therapies.     

A STUDY TO COMPARE THE EFFICACY OF TWO METHODS OF SKIN PREPARATION PRIOR TO JOINT INJECTION

This paper compares two methods of skin preparation in termsof their effectiveness in rendering the skin sterile, ease ofuse, and their cost. KEY WORDS: Skin preparation, Joint injection, Joint infection     

The role of iron in an acute model of skin inflammation induced by reactive oxygen species (ROS)

The effect of iron was studied in rats in a ROS-initiated model of acute skin inflammation. Iron dextran was administered i.v. 24 h before the induction of the inflammatory response by intradermal injection of glucose oxidase attached to polyethylene glycol (GOD-PEG). Iron exacerbated the response at 24 and 48 h (P greater than 0.001). Histologically, a similar picture was seen to that without iron except for an increase in tissue oedema and matrix destruction including the skin glands. Associated with iron loading was an increase in Perls stainable iron in the skin (P greater than 0.025) and liver (P greater than 0.001). However, skin inflammation without iron loading also increased skin iron levels (P greater than 0.025). Total serum iron was decreased in iron-loaded and GOD-PEG animals (P greater than 0.01) and the unbound iron binding capacity (UIBC) increased (P greater than 0.01).     

Clinical trial: the efficacy and safety of oral PF‐03491390, a pancaspase inhibitor – a randomized placebo‐controlled study in patients with chronic hepatitis C

Aliment Pharmacol Ther 31 , 969–978

Summary

Background Elevated serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) reflect hepatocellular injury in patients with chronic hepatitis C virus (HCV). Increased apoptosis and activated caspases are present in these patients. PF‐03491390 inhibits multiple caspases and lowers serum AST and ALT levels in patients with chronic liver diseases. Aim To determine if treatment with an oral pancaspase inhibitor could reduce serum AST and ALT in patients with HCV. Methods Double‐blind, randomized, placebo‐controlled, parallel‐dose study in 204 patients treated with placebo or PF‐03491390 (5, 25 or 50 mg) orally twice daily (b.d.) for up to 12 weeks. Serum AST and ALT were monitored weekly. Results Significant reductions in serum AST and ALT were observed within 1 week of initiating PF‐03491390 in all treatment groups (P < 0.0001). These reductions in AST and ALT were maintained throughout the 12 week treatment period and returned to baseline levels when PF‐03491390 was discontinued. Increasing the dose did not further lower AST or ALT. The most frequently reported adverse events were headache and fatigue. Conclusion PF‐03491390 significantly reduced serum AST and ALT levels in patients with chronic HCV, and was well tolerated over 12 weeks.     

Prehospital Thrombolysis in Acute Myocardial Infarction Salvages Myocardium

Early thrombolysis can be given at home, by a medical intensive care unit ambulance team, in the emergency room, or in the coronary care unit. Thrombolysis should be given very early (<2 or 4 hours) and reestablish normal or near normal coronary blood flow. Methods of management include home monitoring of high risk patients with a transtelephonic 12-lead monitor ECG, the management of the patient at home by a trained GP, physician, or medical technician controlled intensive care ambulance team, or a rapid "door to needle" time in the emergency room. Each of these systems requires patient and physician reeducation, to make each group aware of the advantages of early and complete revascularization. An alternative fast track can be provided by immediate percutaneous transluminal coronary angioplasty if the hospital can be prewarned by the physician outside. This article reviews the current published literature and also our experience in 760 patients in Jerusalem. Infarct size, complication rate, and long-term prognosis is related to early complete restoration of coronary blood flow.     

Effects of the antimigraine compound zolmitriptan ('Zomig') on psychomotor performance alone and in combination with diazepam in healthy volunteers

Zolmitriptan (Zomig^TM) is a 5HT_1B/1D agonist which has the ability to cross the intact blood-brain barrier to access central as well as peripheral receptors. Because of the potential for central nervous system side effects, this randomized, double-blind, placebo-controlled, 6-period crossover study evaluated the effects of 2.5 and 5 mg doses of zolmitriptan on psychomotor performance and investigated any pharmacodynamic or pharmacokinetic interaction with diazepam. Twelve healthy volunteers received the following "treatments" as single doses: zolmitriptan 2.5 mg, zolmitriptan 5 mg, diazepam 10 mg, zolmitriptan 2.5 mg+diazepam 10 mg, zolmitriptan 5 mg+diazepam 10 mg and placebo. Pre-dose and at 1, 4, 8, and 24 h post-dose, the following validated battery of psychomotor tests was performed: Bond-Lader visual analogue scales (calmness, contentedness, and alertness factors), critical flicker fusion test, choice reaction time (recognition, motor, and total reaction times), finger-tapping test, number cancellation test and digit symbol substitution test. Plasma concentrations of zolmitriptan, its active metabolite, and diazepam and its active metabolites were measured at the same timepoints. Zolmitriptan 2.5 and 5 mg had no effect on psychomotor function when given alone. In contrast, diazepam 10 mg had profound effects, consistent with its sedative properties, but there was no synergism on concomitant administration of either dose of zolmitriptan. Plasma concentrations of zolmitriptan, diazepam, and their respective active metabolites were similar when the two drugs were given alone or in combination.