Biomedical subjects
Publications and source records attributed to F K Welsh.
Explore the source record for details and available documents.
Methods of selection of candidates for training in surgery has long been regarded as lacking explicit criteria and objectivity. Our purpose was to discover the aptitudes and personality types of applicants for surgical posts at the outset, in order to discover which were most likely to result in a satisfactory progression through training and which were associated with career difficulties. This longitudinal predictive validation study has been undertaken in a London Teaching Hospital since 1994. After short-listing, but immediately before interview, all candidates for senior house officer posts in basic surgical training and in geriatric medicine were asked to undertake psychometric tests of numerical (GMA) and spatial (SIT7) reasoning, personality type (MBTI), and self-rating of competency. There were no differences in ability scores between surgeons or geriatricians. Personality differences were revealed between the surgeons and the geriatricians, and between male and female surgeons. This study suggests that while there are no differences in ability between surgeons and geriatricians at the start of training, there are differences in personality. Long-term follow-up of the career development of this cohort of surgical SHOs is required to determine whether the psychometric measures described correlate with achievements of milestones in their surgical careers.
OBJECTIVE: To examine the effects of cholestatic jaundice on gut barrier function. SUMMARY BACKGROUND DATA: Gut barrier failure occurs in animal models of jaundice. In humans, the presence of endotoxemia indirectly implicates failure of this host defense, but this has not previously been investigated in jaundiced patients. METHODS: Twenty-seven patients with extrahepatic obstructive jaundice and 27 nonicteric subjects were studied. Intestinal permeability was measured using the lactulose-mannitol test. Small intestinal morphology and the presence of mucosal immunologic activation were examined in endoscopic biopsies of the second part of the duodenum. Systemic antiendotoxin core IgG antibodies and serum interleukin-6 and C-reactive protein were also quantified. Intestinal permeability was remeasured in 9 patients 5 weeks after internal biliary drainage. RESULTS: The median lactulose-mannitol ratio was significantly increased in the jaundiced patients. This was accompanied by upregulation of HLA-DR expression on enterocytes and gut-associated lymphoid tissue, suggesting immune activation. A significant increase in the acute phase response and circulating antiendotoxin core antibodies was also observed in the jaundiced patients. After internal biliary drainage, intestinal permeability returned toward normal levels. CONCLUSIONS: A reversible impairment in gut barrier function occurs in patients with cholestatic jaundice. Increased intestinal permeability is associated with local immune cell and enterocyte activation. In view of the role of gut defenses in the modern paradigm of sepsis, these data may directly identify an important underlying mechanism contributing to the high risk of sepsis in jaundiced patients.
BACKGROUND: The integrity of the gastrointestinal mucosa is a key element in preventing systemic absorption of enteric toxins and bacteria. In the critically ill, breakdown of gut barrier function may fuel sepsis. Malnourished patients have an increased risk of postoperative sepsis; however, the effects of malnutrition on intestinal barrier function in man are unknown. AIMS: To quantify intestinal barrier function, endotoxin exposure, and the acute phase cytokine response in malnourished patients. PATIENTS: Malnourished and well nourished hospitalised patients. METHODS: Gastrointestinal permeability was measured in malnourished patients and well nourished controls using the lactulose:mannitol test. Endoscopic biopsy specimens were stained and morphological and immunohistochemical features graded. The polymerase chain reaction was used to determine mucosal cytokine expression. The immunoglobulin G antibody response to endotoxin and serum interleukin 6 were measured by enzyme linked immunosorbent assay. RESULTS: There was a significant increase in intestinal permeability in the malnourished patients in association with phenotypic and molecular evidence of activation of lamina propria mononuclear cells and enterocytes, and a heightened acute phase response. CONCLUSIONS: Intestinal barrier function is significantly compromised in malnourished patients, but the clinical significance is unclear.
BACKGROUND: Upregulation of major histocompatibility complex (MHC) class II antigen in response to the T-cell lymphokine interferon-gamma (IFN-gamma) is central to T cell-macrophage cooperation and immune homeostasis. We evaluated this property in malnourished surgical patients and assessed the impact of nutrition repletion with total parenteral nutrition (TPN). METHODS: Sixty-two patients were studied: 37 malnourished and 25 controls. Whole blood was cultured with or without IFN-gamma (100 U mL-1), dual-labeled with anti-CD14 (monocyte) and anti-human leukocyte antigen-DR antibodies and analyzed by flow cytometry. Phagocytosis was measured by flow cytometry. In a second study, 10 severely malnourished patients received 5 days of TPN and MHC class II expression was measured at the end of this period. RESULTS: The magnitude of the increase in monocyte MHC class II expression in response to IFN-gamma was significantly increased in the control group compared with the malnourished group (107% vs 53%; p < .05). This impairment directly correlated with severity of malnutrition, but did not correlate with age or disease type. The number of bacteria phagocytozed per cell was significantly decreased (p < .05) in the malnourished group. In study 2, there was a significant increase in MHC class II induction with IFN-gamma after short-term TPN (58% before vs 173% after, p < .001). CONCLUSIONS: MHC class II induction in response to IFN-gamma is significantly impaired in malnourished patients, correlating with the severity of malnutrition. This defect is reversed by short-term TPN. These data identify the reversible loss of a key mechanism, fundamental to host defense, that may enhance the risk of infection in malnourished patients.
BACKGROUND: Direct experimental evidence suggests that total enteral nutrition (TEN) reduces septic morbidity compared with bowel rest and total parenteral nutrition (TPN) and that mucosal support and maintenance of gut barrier function is a key mechanism. This effect is supported indirectly by clinical studies, but this question has not previously been investigated directly in the postoperative patient. This study examined the hypothesis that early enteral feeding after major upper gastrointestinal surgery may modulate gut barrier function and decrease the risk of major infective complications compared with bowel rest and parenteral nutrition. METHODS: A randomized clinical trial of 67 patients (TPN = 34; TEN = 33) fed postoperatively for 7 days was performed. Thirty-day major morbidity and mortality were monitored. Intestinal permeability was measured using the lactulose/mannitol test preoperatively and on postoperative days 1 and 7. Systemic anti-endotoxin core immunoglobulin G and M antibodies and serum albumin and C-reactive protein were quantified at these time points. RESULTS: No clinical benefit was observed in patients fed enterally compared with the parenterally fed group. Intestinal permeability was increased on the 1st postoperative day in association with evidence of endotoxin exposure. By day 7, enteral feeding compared with parenteral feeding had failed to significantly influence any of the gut barrier or systemic parameters. CONCLUSIONS: This randomized controlled trial of TEN vs TPN after major upper gastrointestinal surgery failed to show a clinical benefit for the enteral route. Moreover, enteral nutrition did not modulate gut barrier function postoperatively.