Genetic association studies of interleukin-13 receptor alpha1 subunit gene polymorphisms in asthma and atopy.

Interleukin (IL)-13 plays a central role in asthma pathogenesis by binding to the IL-13 receptor, which is a heterodimer composed of the IL-13 receptor alpha1 subunit (IL-13Ralpha1) and IL-4Ralpha. The genetic diversity at the IL-13Ralpha1 gene (IL13RA1) locus on chromosome Xq24 was characterised and the association of identified polymorphisms with asthma and atopy phenotypes examined. The promoter and coding region of IL13RA1 were screened for common genetic variants, and polymorphisms found were genotyped in a large cohort of 341 asthmatic Caucasian families (each containing at least two asthmatic siblings) and 182 nonasthmatic control subjects. Genetic association was determined using case-control and transmission disequilibrium test analyses. Two common polymorphisms were identified, a newly found thymidine (T) to guanine (G) transition of nucleotide -281 (-281T>G) single nucleotide polymorphism in the IL13RA1 promoter and the previously described 1365A>G variant in the IL13RA1 proximal 3' untranslated region. No significant association of either -281T>G or 1365A>G with risk of asthma or atopy phenotypes was found, apart from a suggestive association between the IL13RA1 -281T/1365A haplotype and raised total serum immunoglobulin E levels in adult female asthmatics. These findings indicate that the interleukin-13 receptor alpha1 subunit gene -281T>G and 1365A>G polymorphisms do not contribute to asthma susceptibility or severity, although the interleukin-13 receptor alpha1 subunit gene locus might be involved in the control of immunoglobulin E production.     

Is infrainguinal bypass grafting successful following failed angioplasty?

OBJECTIVES: Angioplasty is often used in the management of lower limb ischaemia and can reduce the need for infrainguinal bypass in some patients. There is an associated failure rate with this technique and bypass surgery is often used in this situation as a secondary limb salvage procedure. We aimed to evaluate the outcome of infrainguinal bypass grafting following failed attempt at angioplasty. METHODS: All cases of infrainguinal bypass at a single centre over a seven year period were identified and notes reviewed. Cases were divided into four groups according to their indication for surgery; acute ischaemia, chronic critical ischaemia, failed angioplasty and an 'other' group including aneurysmal disease and claudicants. The failed angioplasty group was compared with the other three groups. Survival analysis was performed using Kaplan Meier curves and groups compared in terms of long term patency and survival. RESULTS: Primary patency was 61.2% in the failed angioplasty group at 12 months compared with 60.6% in the other groups (P=1.11). There was also no significant difference in primary patency at 60 months (50% vs 40.6%, P=0.26). Survival at 12 months was also comparable between the groups (failed angioplasty group 74.2% compared with 77.3% in the other groups, P=0.662) as was 60 months survival (33.3% and 35.4% respectively, P=0.166). DISCUSSION: In this study, outcome of infrainguinal bypass following failed angioplasty was comparable to outcome of surgery performed for another indication. This paper supports the use of distal bypass surgery for limb salvage in cases where minimal access techniques have failed.     

Calciphylaxis – a topical overview

'Calciphylaxis', a calcification syndrome associated with ischaemic cutaneous necrosis, is acquired naturally in humans in disease states. It is a life and limb-threatening complication, usually observed in patients with renal disease and secondary hyperparathyroidism, but known to occur in the absence of renal or parathyroid disease. The reported mortality rate, which ranges from 60-80%, relates to wound infection, sepsis and organ failure. It is a small-vessel vasculopathy, which is estimated to occur in about 4% of haemodialysis patients. Clinically, violaceous, reticulate areas of cutaneous necrosis and eschar may be evident, particularly in the extremities. In addition to the clinical picture, a raised calcium phosphorous product, an elevated parathyroid hormone level, radiographic evidence of vessel and soft-tissue calcification and the finding of mural calcification affecting small arteries and arterioles on histopathology help to confirm the diagnosis of this entity which generally has a poor prognosis. A high index of suspicion and an active multidisciplinary management approach, with rigorous attention to wound care and prevention of sepsis, are vital in the management of these patients. In this overview, we discuss the pathophysiology, clinical features and associations, risk factors, diagnosis and management issues relating to calciphylaxis.     

Presentation of abdominal tuberculosis to general surgeons.

Abdominal tuberculosis (TB) continues to give rise to diagnostic and therapeutic challenges. A total of 24 patients with abdominal TB who presented to general surgeons over a 9-year period have been reviewed. Most (92 per cent) of these patients were Asian; only one had a past history of pulmonary TB. The most common presenting complaint was abdominal pain in 21 patients (88 per cent) with the associated symptoms of weight loss in 18 (75 per cent), anorexia in 15 (62 per cent) and night sweats in 13 (54 per cent). A tissue diagnosis was obtained in 18 patients (75 per cent) and 17 patients (71 per cent) underwent laparotomy. These results show that the diagnosis of abdominal TB is still difficult to establish, and that many patients undergo laparotomy despite the existence of less invasive diagnostic procedures.     

The Sigma-trial protocol: a prospective double-blind multi-centre comparison of laparoscopic versus open elective sigmoid resection in patients with symptomatic diverticulitis

Backround  

Diverticulosis is a common disease in the western society with an incidence of 33–66%. 10–25% of these patients will develop diverticulitis. In order to prevent a high-risk acute operation it is advised to perform elective sigmoid resection after two episodes of diverticulitis in the elderly patient or after one episode in the younger (< 50 years) patient. Open sigmoid resection is still the gold standard, but laparoscopic colon resections seem to have certain advantages over open procedures. On the other hand, a double blind investigation has never been performed. The Sigma-trial is designed to evaluate the presumed advantages of laparoscopic over open sigmoid resections in patients with symptomatic diverticulitis.     

Ischaemia-reperfusion injury and regional inflammatory responses in abdominal aortic aneurysm repair.

OBJECTIVES: The inflammatory response to abdominal aortic aneurysm repair is likely to result in response to an ischaemia-reperfusion injury (IRI) to the lower-limbs and gastrointestinal tract. This paper reviews the pathogenesis of the inflammatory response to abdominal aortic aneurysm repair, with specific reference to the levels of evidence in the current literature regarding the potential origin of the inflammatory response. DESIGN: Review article. METHODS: The current literature (1966 to August 2003) was reviewed specifically for all articles employing techniques of regional blood sampling from the venous drainage of the lower limbs or gastrointestinal tract during abdominal aortic aneurysm repair. RESULTS: Ten relevant studies were identified. These demonstrated that regional blood sampling techniques could be easily performed, and provided useful information regarding the potential sites of origin of the inflammatory response. CONCLUSIONS: Regional blood sampling techniques provide useful information regarding the potential sites of origin of the inflammatory response. Current evidence suggests that both the lower limbs and gastrointestinal tract are clearly important in their roles, however more work is now required to compare directly the roles and contributions of the lower limbs and gastrointestinal tract to the inflammatory response during abdominal aortic aneurysm repair.