Search PubMed⌕ Search

Biomedical subjects

G L Carlson

Publications and source records attributed to G L Carlson.

At least 19 recordsLinked to original sources
PubMed2005

Targets and elective colorectal cancer: outcome and symptom delay at surgical resection.

OBJECTIVE: To determine, for elective patients with colorectal cancer, if associations exist between the length of symptom history at surgical resection and Dukes stage, completeness of the surgical procedure and patient survival. PATIENTS AND METHODS: A prospective cohort study was undertaken. Five hundred and eighty-two patients with colorectal cancer, admitted for surgical resection after outpatient consultation, divided into four equal quartiles according to length of symptom history (short: n = 131, 0-103 days; medium: n = 136, 104-177 days; long: n = 136, 178-318 days; very long: n = 137, 319-1997 days). The main outcome measures used were the Extent of tumour (Dukes stage) at resection, completeness of resectional surgery (curative vs palliative), patient survival after resection. RESULTS: For patients undergoing elective surgical resection of colorectal cancer we did not find an association between Dukes stage and duration of patient history (Dukes stage C tumours were seen in 37% (CI: 26.2%-48.0%) of patients with a short symptomatic history as opposed to 34% (CI: 32%-62%) with a very long symptomatic history). Elective curative resection was not associated with a significantly different symptom duration than elective palliative resection (Palliative resections were performed in 24% (CI: 11.7%-36.4%) of patients with a short symptomatic history as opposed to 16% (CI: 2.4%-29.9%) with a very long symptomatic history). The median survival time for the four elective colorectal patient groups defined by length of symptomatic history was not significantly different - (short: n = 131, 4.3 years; medium: n = 136, 5.9 years; long: n = 136, 7.1 years; very long: n = 137, 5.0 years). CONCLUSION: Tumour extent, completeness of resection and patient outcome after elective colorectal cancer resection was not found to have an association with length of patient history at the time of surgery.

Chi-Square Distribution↗
PubMed2004

Fistuloclysis can successfully replace parenteral feeding in the nutritional support of patients with enterocutaneous fistula.

BACKGROUND: Use of total parenteral nutrition (TPN) in patients with acute intestinal failure due to enteric fistulation might be avoided if a simpler means of nutritional support was available. The aim of this study was to determine whether feeding via an intestinal fistula (fistuloclysis) would obviate the need for TPN. METHODS: Fistuloclysis was attempted in 12 patients with jejunocutaneous or ileocutaneous fistulas with mucocutaneous continuity. Feeding was achieved by inserting a gastrostomy feeding tube into the intestine distal to the fistula. Infusion of enteral feed was increased in a stepwise manner, without reinfusion of chyme, until predicted nutritional requirements could be met by a combination of fistuloclysis and regular diet, following which TPN was withdrawn. Energy requirements and nutritional status were assessed before starting fistuloclysis and at the time of reconstructive surgery. RESULTS: Fistuloclysis replaced TPN entirely in 11 of 12 patients. Nutritional status was maintained for a median of 155 (range 19-422) days until reconstructive surgery could be safely undertaken in nine patients. Two patients who did not undergo surgery remained nutritionally stable over at least 9 months. TPN had to be recommenced in one patient. There were no complications associated with fistuloclysis. CONCLUSION: Fistuloclysis appears to provide effective nutritional support in selected patients with enterocutaneous fistula.

Adult↗
PubMed2004

Randomized clinical trial of the effects of immediate enteral nutrition on metabolic responses to major colorectal surgery in an enhanced recovery protocol.

BACKGROUND: The effects of immediate postoperative enteral nutrition on postoperative nitrogen balance and insulin resistance were studied in patients subjected to an enhanced-recovery protocol. METHODS: Eighteen patients undergoing major colorectal surgery in an enhanced-recovery protocol were randomized to immediate postoperative enteral feeding for 4 days with either complete or hypocaloric nutrition. Nitrogen balance and changes in glucose kinetics, substrate utilization (indirect calorimetry) and insulin sensitivity (hyperinsulinaemic-euglycaemic clamp) were measured. Values are mean(s.e.m.). RESULTS: Mean postoperative urinary nitrogen losses were low (10.7(1.0) versus 10.5(0.7) g per day for complete versus hypocaloric nutrition) and insulin resistance was insignificant (-20(7) versus -27(11) per cent), with no difference between groups. Complete enteral feeding was given without hyperglycaemia (blood glucose concentration 5.8(0.4) versus 5.0(0.4) mmol/l) and resulted in nitrogen balance (+0.1(0.8) versus -12.6(0.6) g nitrogen per day; P < 0.001). CONCLUSION: This enhanced-recovery protocol was associated with minimal postoperative insulin resistance and nitrogen losses after surgery. Immediate postoperative enteral nutrition was provided without hyperglycaemia and resulted in nitrogen balance.

Blood Glucose↗
PubMed2004

Systematic review of genetic influences on the prognosis of colorectal cancer.

BACKGROUND: In terms of genetics, colorectal cancer is one of the best understood of all malignant diseases. Genetic influences on prognosis may have far-reaching implications, especially for the design of surgical and chemoradiotherapeutic regimens. However, their significance in determining prognosis remains unclear. This study aimed to review the literature on the specific role of key genes in determining the survival of patients with colorectal cancer. METHODS: A Medline search was carried out to identify all original scientific papers relating colorectal cancer genetics to patient survival, up to December 2002. Cochrane and Embase databases were also searched. Identified articles were retrieved and searched carefully for additional information. This review includes K-ras, p53, DCC, NM23 and DNA mismatch repair genes. RESULTS AND CONCLUSION: Conflicting evidence exists as to the prognostic significance of genes commonly implicated in the pathogenesis of colorectal carcinoma. Possible causes for such discrepancy include differences in study methods and laboratory techniques, variable duration of follow-up, statistical differences in study power, and heterogeneity in study populations. Future studies should adopt standardized protocols to define clinically relevant genetic observations.

Base Pair Mismatch↗
PubMed2004

Opiate withdrawal syndrome mimicking postoperative intestinal obstruction.

Patients with complicated inflammatory bowel disease commonly undergo repeated surgical procedures, often against a background of chronic opiate use. We describe a case in which a postoperative attempt to withdraw opiate analgesia on two separate occasions led to a clinical syndrome strongly suggestive of intestinal obstruction, the signs and symptoms of which settled rapidly on re-introduction of opiates. Small bowel contrast studies indicated a level of obstruction which not only fluctuated, but occurred at an unusual site for mechanical obstruction. In patients with a history of long-standing opiate use, postoperative opiate withdrawal can cause a significant, functional bowel disorder and should be borne in mind in the differential diagnosis of postoperative intestinal obstruction. Patients can be treated effectively with clonidine.

Adult↗
PubMed2003

Surgical management of intestinal failure.

Surgery plays a key role in the management of both acute and, less frequently, chronic intestinal failure. Acute intestinal failure frequently requires surgical treatment when it arises as a consequence of intestinal fistulation or obstruction. In specialised clinical practice approximately 50% of acute intestinal failure is associated with intestinal fistulas and in approximately 50% of patients, this condition arises as part of the natural history or complicating treatment for Crohn's disease. A considerable proportion of such patients have abdominal infection and present complex nutritional and metabolic problems. The most important aspect of the surgical management of patients with acute intestinal failure associated with intra-abdominal infection is management of sepsis, since recovery is unlikely in the presence of active infection. Moreover, effective nutritional support and restoration of body composition is not possible if sepsis remains unresolved. Surgical strategies to deal with intra-abdominal infection may involve percutaneous drainage, laparotomy and resection of fistulating segments of intestine and, when infection is persistent and contamination extensive, laparostomy (a technique in which the abdomen is left open and allowed to heal by secondary intention). Surgical treatment should not only be timely and effective, but also aimed at preventing secondary damage to the small intestine, in order to minimise the risk of short bowel syndrome. In some cases a proximal defunctioning stoma may be required, with prolonged nutritional support, using either home total parenteral nutrition or feeding via the defunctioned distal gut (fistuloclysis), pending restoration of intestinal continuity. The role of surgical treatment for patients with short bowel syndrome is less clear. While surgery is frequently required for the management of complications of short bowel syndrome (including gallstones and possibly peptic ulcer disease), the role of intestinal lengthening and tapering procedures (to increase functional intestinal length), and artificial valves, reversed segments and colonic interposition (to reduce intestinal transit) remains controversial. For some patients with short bowel syndrome and, in particular, those with combined intestinal and hepatic failure, intestinal transplantation may become the treatment of choice as long-term results continue to improve.

Acute Disease↗
PubMed2003

Glutamine deprivation facilitates tumour necrosis factor induced bacterial translocation in Caco-2 cells by depletion of enterocyte fuel substrate.

BACKGROUND AND AIMS: Factors that induce luminal bacteria to cross the intestinal epithelium following injury remain poorly defined. The aim of this study was to investigate the interaction between glutamine metabolism, energy supply, and inflammatory mediators in determining the translocation of non-pathogenic bacteria across cultured enterocytes. METHODS: The effect of tumour necrosis factor alpha (TNF-alpha) on translocation of Escherichia coli C25 across Caco-2 epithelial monolayers was studied in the presence of products and inhibitors of glutamine metabolism. Simultaneous measurements of transepithelial electrical resistance (TEER) and flux of lucifer yellow were used to assess effects on the paracellular pathway. Lactate dehydrogenase release was used to monitor enterocyte integrity. Imaging of monolayers in these experimental conditions was undertaken with transmission electron microscopy. RESULTS: Exposure to basolateral TNF-alpha (20 ng/ml) for six hours induced translocation of E coli across Caco-2 but only if accompanied by simultaneous glutamine depletion (p<0.01). Translocation was inhibited by addition of glutamine for two hours (p<0.01) but not by an isonitrogenous mixture of non-glutamine containing amino acids. Inhibition of glutamine conversion to alpha-ketoglutarate, but not blockade of glutathione or polyamine synthesis, also induced translocation in the presence of TNF-alpha. Manipulations that induced bacterial translocation were associated with a marked reduction in enterocyte ATP levels. No effect of these treatments on paracellular permeability or lactate dehydrogenase release was observed. Conditions in which translocation occurred were associated with the presence of bacteria within enterocyte vacuoles but not the paracellular space. CONCLUSIONS: In inflammatory conditions, the availability of glutamine as an enterocyte fuel substrate is essential for the preservation of a functional barrier to microorganisms. In conditions of acute glutamine depletion, cytokine mediated bacterial translocation appears to be primarily a transcellular process.

Adenosine Triphosphate↗
PubMed2002

Anti-secretory properties of non-peptide somatostatin receptor agonists in isolated rat colon: luminal activity and possible interaction with P-glycoprotein.

1. The diverse physiological actions of somatostatin are mediated by a family of G-protein coupled receptors (SSTRs). Several peptide analogues of somatostatin such as octreotide have been developed for therapeutic use, including treatment of gastrointestinal disorders such as secretory diarrhoea. However, their development as anti-diarrhoeal agents has been limited by poor oral bioavailability, necessitating parenteral administration. This in vitro study investigated the anti-secretory potential of a group of novel, non-peptide, somatostatin-receptor agonists that selectively activate specific SSTR subtypes to assess their potential for oral administration. 2. The ability of the agonists to inhibit forskolin-stimulated chloride secretion was measured using a sensitive bioassay system in isolated rat colonic mucosa. 3. The SSTR-2 selective agonist, L-779,976 was 10-times more potent than octreotide as an inhibitor of secretion when added to the basolateral surface of rat colon. Non-peptide agonists selective for SSTR1 (L-797,591), SSTR3 (L-796,778), SSTR4 (L-803,087) or SSTR5 (L-817,818) showed little or no anti-secretory activity in this preparation. 4. L-779,976 was able to inhibit secretion when applied to the luminal surface at sub-micromolar concentrations suggesting that it can cross the colonic epithelium. The anti-secretory potency of luminal L-779,976 was increased 3 fold in the presence of GF120918, a known inhibitor of P-glycoprotein. 5. Non-peptide somatostatin receptor agonists may provide a basis for the development of new, orally available anti-diarrhoeal therapies.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2001

Mechanisms of intestinal failure in Crohn's disease.

PURPOSE: The purpose of this study was to determine the mechanisms by which patients with Crohn's disease develop intestinal failure and, in particular, to assess the relative importance of severe primary disease, repeated uncomplicated elective small intestine resection, and resection performed as a consequence of intra-abdominal septic surgical complications. METHODS: This was a retrospective analysis of 41 patients with Crohn's disease referred to a specialized intestinal failure unit between January 1987 and September 1998 for permanent home parenteral nutrition. To compare the surgical activity in patient groups, a resection index was calculated by dividing the number of intestinal resections by the interval in years between the first resection for Crohn's disease and referral for management of intestinal failure. RESULTS: Extensive primary Crohn's disease was responsible for intestinal failure in 7 cases (17 percent). The remainder (n = 34, 83 percent) developed intestinal failure after intestinal resection. Nine of the "surgical" Crohn's patients developed intestinal failure after uncomplicated sequential resection, (median small-bowel length 65 (range, 60-120) cm) after a median of 3 (range, 2-8) operations over a median of 17 (range, 3-27) years. By contrast, the other 25 surgical Crohn's patients developed intestinal failure after multiple unplanned laparotomies for intra-abdominal sepsis (median small-bowel length 70 (range, 60-200) cm), with a median of 4 (range, 2-7) laparotomies performed over a median of 0.5 (range, 0.1 to 1.5) years (P < 0.001). The resection index for the 25 Crohn's patients undergoing laparotomies for intra-abdominal sepsis was significantly greater than that of the 9 patients who had planned sequential resections (2.1 (0.27-25) vs. 0.23 (0.1-1.0); P < 0.002, Mann-Whitney U test). CONCLUSION: Intestinal failure develops in Crohn's disease primarily as a result of complications of surgical treatment. The largest group of patients at risk consists of those who are undergoing multiple unplanned laparotomies to control intra-abdominal sepsis.

Adult↗
PubMed2001

Insulin resistance and glucose-induced thermogenesis in critical illness.

Critical illness is associated with a marked increase in metabolic rate and progressive wasting, despite aggressive nutritional support. The metabolic events which are responsible for these phenomena are unclear, but are characterised by marked impairment of the anabolic effects of insulin on glucose metabolism and excessive activation of the sympathetic nervous system. It has been suggested that critical illness may be associated with impaired carbohydrate oxidation and a marked increase in the loss of heat energy associated with glucose administration (glucose-induced thermogenesis). This situation may result in impaired efficiency of nutrient assimilation. Studies employing combinations of nutrient infusions both at clinically-relevant rates and in association with euglycaemic hyperinsulinaemia have, however, demonstrated that nutrient-induced thermogenesis is unaffected in critical illness in human subjects, and that defective glucose utilization occurs as a consequence of impaired insulin-mediated glucose storage rather than oxidation. Although the cellular and molecular mechanisms underlying these changes are controversial, the recent validation of a human model of insulin resistance in critical illness should provide a means of studying this response in future, and allow the identification of therapeutic targets. This information should increase the efficacy of nutritional support in some of our most seriously-ill patients.

Animals↗
PubMed2001

Kinetic profiling of P-glycoprotein-mediated drug efflux in rat and human intestinal epithelia.

Intestinal drug efflux mediated by P-glycoprotein and other ABC transporters is widely accepted as a reason for low or variable oral absorption. However, little is known about species and regional differences in P-glycoprotein so the functional and predictive relevance of observations made in cell models such as Caco-2 is uncertain. The aim of this study was to define the kinetics of drug efflux in rat and human intestinal tissues in vitro using the "reference" substrates digoxin and vinblastine. The expression and functional role of other ABC transporters in the transport of these compounds was also investigated. Saturable, verapamil-sensitive efflux of digoxin was observed in all intestinal regions. Apparent affinity of the efflux process varied within a relatively narrow range (50-92 microM), increasing in rat from small to large intestine. In contrast, maximal transporter activity varied over a 4- to 5-fold range with ileum > jejunum > colon. Similar regional differences in efflux were also observed with vinblastine. Maximal efflux levels were similar in Caco-2 and ileum for both substrates, suggesting that Caco-2 may quantitatively predict small intestinal drug efflux. Digoxin efflux kinetics was virtually identical in rat and human colon. Inhibitor studies showed that digoxin and vinblastine efflux in intestinal tissues was mediated by P-glycoprotein, although a minor component could be attributed to multidrug resistance-related protein (MRP)-like transporters in Caco-2. This study has analyzed the differential functional expression of drug efflux along the gastrointestinal tract. Such data will be critical in developing predictive models of P-glycoprotein-mediated efflux using information gathered from in vitro systems.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2000

The staged management of complex entero-urinary fistulae.

OBJECTIVE: To present the results of the staged management of complex entero-urinary fistulae. PATIENTS AND METHODS: Ten patients with complex entero-urinary fistulae were reviewed; all patients were referred to a national intestinal failure unit after failed treatment in other centres. Each patient was treated in three stages. The acute stage involved proximal defunctioning and distal drainage of both the gastrointestinal and urinary tracts to isolate the fistula, together with the eradication of sepsis. The recovery stage involved total parenteral nutrition, organ support, radiological planning of surgical reconstruction and intensive nursing. The reconstructive stage followed when the patient was stable, nutritionally replenished and intra-abdominal sepsis was controlled. Surgery was undertaken jointly by urological and gastrointestinal surgeons. RESULTS: The fistulae were treated successfully in all patients, with functional restoration in four, and/or diversion of the gastrointestinal and urological tracts in six. The mean (range) time to reconstruction was 5 (1-20) months. There were no postoperative deaths. CONCLUSION: A staged multidisciplinary approach with delayed reconstruction can achieve a successful outcome in the management of complex entero-urinary fistulae.

Adult↗
PubMed2000

Insulin resistance and substrate utilization in human endotoxemia.

Infection results in a state of insulin resistance, but the pathogenesis is poorly understood. Intravenous administration of bacterial lipopolysaccharide (LPS) has been used to mimic the febrile and systemic inflammatory responses to infection, but it is unclear whether LPS induces insulin resistance in man. To investigate the effects of LPS on insulin sensitivity and substrate utilization, we administered, in paired cross-over studies, either 20 U/kg Escherichia coli endotoxin or saline control to healthy volunteers (n = 6) 120 min after the start of a 10-h euglycemic hyperinsulinemic clamp (insulin infusion rate, 80 mU/m2 x min). LPS induced a fever, tachycardia, and mild arterial hypotension. Glucose utilization increased abruptly 120 min after LPS administration (+64.1+/-12.0%; P < 0.003), but then declined progressively, and insulin resistance was evident by 420 min (+1.9+/-3.5%; P < 0.05). The reduction in glucose utilization, like that observed in sepsis, was related to impaired nonoxidative glucose disposal and not abnormal glucose oxidation. The cortisol and GH responses to LPS were of sufficient duration and magnitude to explain the insulin resistance. LPS administration results in metabolic responses very similar to those observed in sepsis and could provide a useful model for the study of insulin resistance in human critical illness.

Adult↗