Hypoxia determines survival outcomes of bacterial infection through HIF-1alpha dependent re-programming of leukocyte metabolism.

Hypoxia and bacterial infection frequently co-exist, in both acute and chronic clinical settings, and typically result in adverse clinical outcomes. To ameliorate this morbidity, we investigated the interaction between hypoxia and the host response. In the context of acute hypoxia, both S. aureus and S. pneumoniae infections rapidly induced progressive neutrophil mediated morbidity and mortality, with associated hypothermia and cardiovascular compromise. Preconditioning animals through longer exposures to hypoxia, prior to infection, prevented these pathophysiological responses and profoundly dampened the transcriptome of circulating leukocytes. Specifically, perturbation of HIF pathway and glycolysis genes by hypoxic preconditioning was associated with reduced leukocyte glucose utilisation, resulting in systemic rescue from a global negative energy state and myocardial protection. Thus we demonstrate that hypoxia preconditions the innate immune response and determines survival outcomes following bacterial infection through suppression of HIF-1α and neutrophil metabolism. The therapeutic implications of this work are that in the context of systemic or tissue hypoxia therapies that target the host response could improve infection associated morbidity and mortality.

A prospective audit of fistula-in-ano at St. Mark's hospital.

OBJECTIVE: To conduct a prospective audit of all patients presenting with anal fistula at St. Mark's Hospital during one calendar year and to compare the presentation and outcome of this cohort with previous reports from this institution. PATIENTS AND METHODS: All patients undergoing examination under anaesthetic (EUA) for anal fistula during 1997 were studied. All fistulae were anatomically classified and operative procedures recorded. During a mean follow-up period of 14 months details of healing, recurrence and function were gathered. RESULTS: 98 patients with a mean age of 43.7 years were assessed. 86 (88%) patients had fistulae of cryptoglandular (idiopathic) origin. Fistulae were superficial in 11 (11%) patients, intersphincteric in 30 (31%) patients, trans-sphincteric in 52 (53%) patients, suprasphincteric in 3 (3%) patients and extra-sphincteric in 2 (2%) patients. 49 (50%) fistulae were classified as complex. Eradication of fistulae with preservation of function was achieved in 89 (91%) patients. Fistula recurrence occurred in 4 (4%) cases. Ten (10%) patients had some degree of incontinence, 9 (9%) of whom had undergone previous fistula surgery. Nine (9%) patients still had setons in situ at the end of the follow-up period. CONCLUSIONS: A greater proportion of difficult fistulae was seen during the year compared with previous studies from St. Mark's. Despite this a satisfactory outcome was achieved in the vast majority with a relatively low rate of disturbed function. Previous fistula surgery is a risk factor for incontinence, which can usually be managed conservatively.

An evaluation of the penetration of cefuroxime axetil into human paranasal sinus tissue.

Nineteen patients presenting for sinus surgery were studied to evaluate the percentage penetration from serum to paranasal sinus tissue of a single orally administered dose of cefuroxime axetil. The methods and results are presented. Cefuroxime penetrates well into human sinus mucosa following oral administration and the concentrations obtained exceed minimum inhibitory concentrations of cefuroxime for the most common pathogens in sinusitis.

A stoma jig for surgical craft workshops.

A new jig simulating the abdominal cavity and wall is described. The techniques of defunctioning colostomy and closure of colostomy, end colostomy and ileostomy can be performed. If required the techniques of mass or layered closure of an abdominal incision can also be practised.

Trephine colostomy: a warning.

A case of trephine colostomy is presented in which air insufflation incorrectly identified the distal limb. Disaster was averted by correct identification at laparotomy. The probable cause of the error and methods of avoidance are discussed.

The treatment of perianal and anal condylomata acuminata: a new operative technique.

Seventy-five patients have been treated for condylomata acuminata by means of a new operative approach which results in the preservation of the maximum amount of normal tissue. The technique has proved to be simple to perform, it has minimal complications and causes the patient little in the way of discomfort. Three out of 4 patients treated have no significant recurrent wart formation.

A review of physical abnormalities in familial adenomatous polyposis.

Familial adenomatous polyposis (FAP) is an autosomal dominant condition wherein multiple polyps may be found in the gastrointestinal tract. Initially referred to as familial polyposis coli, it has become evident that virtually all patients with FAP develop adenomas in the upper gastrointestinal tract and thus the syndrome is now termed familial adenomatous polyposis. The number of associated conditions both malignant and benign has been increasingly recognized. Some of these lesions cause morbidity and mortality in affected individuals whilst others act as important clinical markers for identifying patients not yet expressing the phenotype. These abnormalities can arise from tissues of all three primary embryonic layers and are described in this paper.

The anal sphincter.

The anal sphincter has not generally stimulated great scientific interest although anatomical and physiological disorders of this region are common and may be the cause of considerable suffering to the individual affected. Over the last decade there has, however, been an accelerating interest in the function of this important sphincter.