John Hall

The pathobiology of peritonitis.

The peritoneum is more than a mechanical covering that allows for the easy gliding of opposed peritoneal surfaces. The peritoneal mesothelial cells facilitate the action of powerful innate immune mechanisms. In addition, the peritoneal-associated lymphoid tissues contain unique cells that may play a crucial role in the localization of intraperitoneal infection. A clearer understanding of the molecular and cellular events underlying peritoneal functions in both the unstimulated and stimulated state will aid future treatment of peritonitis.

Review: Glutamine and Nucleotide Metabolism Within Enterocytes

Glutamine has an important role as a source of energy for enterocytes. However, it may also have a key role as a source of nitrogen for the synthesis of nucleotides. The relative contribution of de novo synthesis and salvage pathways seems to be affected by the position of enterocytes within the crypt-villus axis as well as the dietary intake of nucleic acids and glutamine. Nucleotides are especially important to enterocytes during intestinal development, maturation, and repair. Hence an understanding of nucleotide metabolism within enterocytes has important implications regarding both the composition and route of administration of nutrient solutions. Many important questions remain unanswered, in particular: Does glutamine stimulate intestinal de novo pyrimidine synthesis via the action of carbamoyl phosphate synthetase I? Can de novo purine synthesis maintain intestinal purine pools in the absence of dietary nucleic acids? And, what are the specific effects of parenterally administered nucleotides on the metabolism and well-being of enterocytes? A greater understanding of these issues will lead to a more rational approach toward the nutritional modulation of gut dysfunction.

Duration of antimicrobial prophylaxis in vascular surgery

BACKGROUNDnThis randomized clinical trial compares the incidence of wound infection after vascular surgery in patients who received prophylaxis using the same antibiotic as either a single-dose or a multiple-dose regimen (until the lines/drain tubes were removed, but not for more than 5 days).nnnMETHODSnEach of the 302 patients who entered the study received ticarcillin 3.0 g/clavulanate 0.1 g (Timentin) intravenously immediately after the induction of anesthesia. Patients randomized to the multiple-dose group received an average of 14.3 doses (range 9 to 20).nnnRESULTSnThe incidence of wound infections was 18% (28 of 153) for patients in the single-dose group and 10% (15 of 149) for patients in the multiple-dose group (P = 0.04; relative risk estimate = 2.00, 95% confidence interval = -1.02 to 3.92).nnnCONCLUSIONSnA multiple-dose antibiotic regimen, rather than single-dose therapy, provides optimal prophylaxis against wound infection for patients undergoing vascular surgery.

Surgery on trial: An account of clinical trials evaluating operations

BACKGROUNDnThe objective of this study was to review published clinical trials to determine the level of compliance with issues relevant to operations.nnnMETHODSnWe evaluated 10 methodologic criteria in 186 trials that were published in 10 prestigious journals between January 1986 and December 1995.nnnRESULTSnOne quarter of the trials failed to provide a clear account of the operative technique, 34% of the trials did not adequately detail the adverse events that occurred after operation, and 40% of the trials neglected to declare the nature and success of the follow-up of patients after the operation. Only 35% of the trials indicated that there was an attempt to standardize either the surgical procedure or perioperative care. In addition, less than 20% of the trials declared a method for assessing compliance with the surgical protocol or commented on the use of resources during the perioperative period.nnnCONCLUSIONSnGreater attention needs to be paid to the specific issues that arise when operations are evaluated in clinical trials.

The Role of Enterocytes in Gut Dysfunction

Stem cells in the intestinal epithelium give rise to enterocytes, goblet cells, enteroendocrine cells, and Paneth cells. Each of these cell lines plays a role in cytoprotection of the intestinal mucosa. In particular, it has been demonstrated that mature enterocytes can act as antigen presenting cells. Parenteral and enteral nutrition are used to nourish critically ill patients. However, these regimens are unfortunately associated with gut atrophy. Glutamine, the preferred intestinal nutrient, reverses this gut atrophy and plays a key role in maintaining the barrier function of the gut. Specific nutrients (putrescine, spermidine, spermine) have been used to modulate intestinal adaption. In addition, ornithine has been shown to act as a regulator of intestinal adaption. In this review, we discuss the relationship between the biology of enterocytes and failure of the gut barrier.