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.     

Evidence of secondary neuronal intestinal dysplasia in a rat model of chronic intestinal obstruction.

The etiology of neuronal intestinal dysplasia remains largely unknown. There is, however, supporting evidence of the existence of Hirschprung's disease or chronic intestinal obstruction associated with neuronal intestinal dysplasia. With the aim of investigating the possible development of neuronal intestinal dysplasia linked to chronic intestinal obstruction, we have examined the enteric nervous system response to long-term obstruction in a rat model. Three different surgical techniques were tested in Wistar male rats. In animals that survived longer than the cutoff chronic intestinal obstruction point (6 weeks), full-thickness biopsies and acetylcholinesterase (AChE), NADH, hematoxylin-eosin, and anti-S100 protein stainings were performed. The results of our model indicate that chronic intestinal obstruction induced different degrees of enteric nervous system dysplasia, including histological features of neuronal intestinal dysplasia. The relationship between chronic intestinal obstruction and anomalies of the enteric nervous system, including neuronal intestinal dysplasia, needs to be further studied.     

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).     

Skeletonization of internal thoracic artery affects its innervation and reactivity.

OBJECTIVE: The studies showing the superior characteristics of ITA graft and its impact on the clinical results of coronary artery surgery were performed with ITA harvested almost exclusively as a pedicle. This study assesses the impact of ITA skeletonization on its innervation and reactivity. METHODS: Segments of skeletonized and non-skeletonized ITA were stained with antibodies against protein S-100 to look for the presence of sympathetic nerve fibers. The functional studies were performed on segments of discarded human pedicled ITA that were divided into two 3mm rings, one skeletonized and another non-skeletonized. We compared concentration-effect relationships for the contraction to norepinephrine and endothelium-dependent relaxation to acetylcholine and bradykinin, as well as endothelium-independent relaxation to sodium nitroprusside in skeletonized and non-skeletonized segments of the same ITA. RESULTS: Skeletonized ITA was devoid of protein S-100 positive nerve fibers. It contracted stronger (maximal response 37.0+/-2.04 vs. 25.4+/-1.83mN (P<0.001)) and was twice as sensitive to norepinephrine: pD(2) 6.03+/-0.10 vs. 5.70+/-0.12 (P=0.035). The endothelium-dependent relaxation responses did not differ between skeletonized and non-skeletonized ITA rings. The skeletonized ITA rings appeared over 10 times more sensitive to sodium nitroprusside: pD(2) 6.66+/-0.20 vs. 5.59+/-0.37 (P=0.012)-potency ratio 11.61. The maximal responses did not differ significantly: 112.0+/-6.71 vs. 129.4+/-16.4% (P=0.33). CONCLUSIONS: Skeletonization results in sympathectomy of ITA. It has no effect on endothelium-dependent relaxation but increases reactivity of ITA to norepinephrine. This augmented response to alpha-agonist is small, in comparison with over a ten-fold increase in sensitivity to sodium nitroprusside. Pedicled and skeletonized ITA are functionally significantly different vessels when studied in vitro.     

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.