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.     

Prolonged suppression of spermatogenesis by oestrogen does not preserve the seminiferous epithelium in procarbazine-treated rats

We examined the hypothesis that induction of reversible testicular atrophy, subsequent to withdrawal of gonadotrophin support, would alleviate the testicular toxicity of the anti-cancer drug procarbazine. In rats, severe but reversible testicular atrophy and suppression of spermatogenesis were induced 56 days after the subcutaneous insertion of a silastic implant containing oestradiol-17 beta. The effect of this treatment upon the testicular toxicity of four weekly doses of procarbazine (200 mg kg-1) was examined 56 days after the termination of procarbazine/oestrogen treatment. At this time the testicular endocrine and spermatogenic functions were close to normal in rats which has received only oestradiol-17 beta. Procarbazine produced severe testicular atrophy which was associated with azoospermia and destruction of the germinal epithelium. Serum LH and FSH concentrations were raised and were associated with low serum concentrations of both testosterone and androgen-binding protein. The combination of procarbazine with the oestrogen treatment did not change any of the testicular toxicity and in some cases it appeared to be exacerbated. In contrast to these experiments other studies have indicated that the testis can be protected if spermatogenesis is reversibly suppressed by other agents which are also active via the pituitary endocrine system. The data would therefore suggest that protection is achieved either by some testicular change other than withdrawal of pituitary gonadotrophin support or that oestradiol-17 beta has additional activity which is permissive for the development of the testicular toxicity of procarbazine.     

Keratin expression in pilosebaceous epithelia in truncal skin of acne patients

Summary This study compared the pattern of keratin expression in pilosebaceous follicles in uninvolved trunk skin of acne patients, comedones, and normal control skin by immunohistochemistry. using both immunofluorescent (IF) and immunoperoxidase (IP) techniques. The shape, size and gross morphology of truncal follicles varied greatly. There was no difference in keratin expression between normal skin and uninvolved skin of patients with acne. The upper part of the pilosebaceous duct expressed keratins K1, K5, K10 and K14, whereas the lower duct expressed keratins K5, K6, K14, K16, K17 and Kl9. The sebaceous gland showed considerable heterogeneity in keratin expression, with some lobules expressing keratins K1, K5, K7, K10, K14 and K17. The comedone wall showed a pattern of keratin expression similar to that of the upper follicle, except that there was, in addition, expression of keratins K6 and K16 suprabasally, and panepithelial expression of K17 in the comedone wall. IF techniques were found to be less sensitive than the IP method in the detection of individual keratins, but the use of multiple antibodies and many different transverse and longitudinal sections of follicles permitted full conclusions to be made. The increased expression of keratins K6, K16 and K17 in the comedone wall is likely to represent a secondary effect of increased cell turnover due to the primary underlying mechanism of comedogenesis. which is as yet unknown.     

A synthetic 10-kD heat shock protein (hsp10) from Mycobacterium tuberculosis modulates adjuvant arthritis

The heat shock protein, hsp10, is an abundant protein in Mycobacterium tuberculosis (Mtb), its nucleotide sequence encoding a protein of 99 amino acids with a molecular mass of 10±7kD. This sequence is phylogenetically conserved, being represented by the GroES homologue of Escherichia coli. Hsp 10 and GroES are members of the chaperonin 10 family of molecular chaperones, and GroES is necessary for the optimal activity of GroEL, a member of the chaperonin 60 family and the E coli homologue of mycobacterial hsp65. Since hsp65 has been implicated in both experimental and human rheumatoid arthritis, we aimed to assess the immunomodulatory effects of its co-chaperonin, hsp10, in experimental arthritis. Our results show that an aqueous solution of a mycobacterial hsp10 delayed the onset and severity of adjuvant-induced arthritis in rodents when administered after disease induction but before joint involvement occurred. This biological activity was specific for the hsp10 of Mtb, since neither GroES nor the rat homologue was effective. Using synthetic hsp10 fragments, the activity was localized to the N-terminal region of the molecule. Assessment of circulating antibody levels to mycobacterial hsp10 and hsp65 indicated that all arthritic rats had increased litres to both hsp10 and hsp65: hsp10-treated rats showed further elevation of this humoral response not only to hsp10 but also to hsp65 when compared with the untreated arthritic control. This is the first report of the immunomodulatory activity of mycobacterial hsp10 in experimental arthritis, and exhibits a potential role for this co-chaperonin in pathophysiological situations.