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Biomedical subjects

B J Rowlands

Publications and source records attributed to B J Rowlands.

At least 55 records · Page 3Linked to original sources
PubMed1998

Renal function in jaundiced patients: a prospective analysis.

A prospective analysis was undertaken to assess renal function in patients with obstructive jaundice. A total of 59 jaundiced patients (serum bilirubin > 100 mumol/l) undergoing biliary decompression by surgical, endoscopic or radiological means received prophylactic fluid volume expansion (3 litres crystalloid fluid intravenously) during the 24 hours before intervention. Renal function (urea and electrolytes, creatinine, creatinine clearance, urinary output) was assessed preoperatively and on days 1-7 and on day 28 postoperatively. Two jaundiced patients (3.4%) developed renal failure (urinary output < 400 ml in 24 hours in the presence of an increased serum urea and/or creatinine) and subsequently died. The overall incidence of post-procedural renal impairment (urinary output < 800 ml in 24 hours) was 10.2%. It is concluded that, with vigilant control of fluid and electrolyte balance and pre-procedural intravenous volume expansion, the incidence of renal dysfunction in patients with obstructive jaundice is not as high as previously reported.

Aged↗
PubMed1997

Intramucosal acidosis and systemic host responses in abdominal aortic aneurysm surgery.

OBJECTIVES: To assess the specific host responses to systemic endotoxemia and tumor necrosis factor (TNF) activation after abdominal aortic aneurysm surgery by measuring antiendotoxin core antibodies (EndoCab) immunoglobulin (Ig)G and IgM, and soluble p55TNF receptor concentrations. The role of the gut in initiating these immune responses was evaluated by correlating the systemic markers to changes in the intramucosal pH of the sigmoid colon. DESIGN: Retrospective, reevaluation study. SETTING: Vascular unit of a university hospital. PATIENTS: Eleven patients who underwent abdominal aortic aneurysm repair surgery were selected from a larger patient cohort (n = 42) on the basis of their clinical outcome (four patients had fatal complications and seven patients had an uneventful recovery). INTERVENTIONS: After induction of anesthesia, intramucosal pH of the sigmoid colon was measured using tonometry. Blood samples were obtained from indwelling catheters or direct venipuncture preoperatively, during surgery, and daily until postoperative day 5. MEASUREMENTS AND MAIN RESULTS: Those patients who died developed intramucosal acidosis of the sigmoid colon intraoperatively. Significant consumption of both IgG and IgM EndoCab antibodies was found in all patients. By measuring the concentration of antibodies to a neutral antigen, i.e., tetanus toxoid, the consumption of IgG EndoCab antibody concentrations was shown to be a specific host response. In all patients, reciprocal changes in the serum concentrations of p55TNF receptor and interleukin (IL)-6 were observed. The percentage increase in p55TNF receptor and the concentration of IL-6 were significantly higher in the nonsurvivor group by 48 hrs. There were significant correlations between, intramucosal pH and EndoCab antibodies, intramucosal pH and p55 TNF receptor, and p55 TNF receptor and IL-6. CONCLUSIONS: The development of colonic ischemia is associated with a significant consumption of IgG EndoCab antibodies and a simultaneous increase in soluble p55TNF receptor. This study provides further support for the concept that gut-derived endotoxin and the generation of TNF may play a role in the pathogenesis of complications after abdominal aortic aneurysm surgery.

Acidosis↗
PubMed1997

An ELISA for measuring tumour necrosis factor alpha in rat plasma.

Tumour necrosis factor (TNF) is a cytokine with multiple biological activities which plays a pivotal role in the response of the body to infection. TNF is secreted in the the monomeric form and associates to yield a biologically active oligomeric molecule. Bioactive TNF can be measured in plasma using cytotoxic assays which employ the murine cell-lines L929 or WEHI 164 clone 13. However, it has become clear that inactive TNF also circulates in vivo, which is not detected by bioassay. These inactive forms may play an important role in the regulation of TNF activity. The rat is often used as a model for the study of acute infection and its systemic effects. Our aim was to develop an ELISA for rat TNF which would provide a convenient and cost effective method of assay. The assay employs two commercially available antibodies raised against recombinant murine TNF (rMuTNF) which exhibit cross-reactivity with rat TNF. The lower limit of detection for this assay was determined to be 39.0 pg/ml rMuTNF. The inter and intra-assay coefficients of variation were < 12.0%. Specificity of the assay was shown by the high degree of parallelism obtained between rMuTNF and commercially available rRatTNF. The assay described measures rat TNF in both plasma and tissue culture supernatant. The measurement of plasma concentrations of TNF using both the ELISA and bioassay may help elucidate more fully the biological importance of TNF.

Animals↗
PubMed1997

Surgical biliary bypass for benign and malignant extrahepatic biliary tract disease.

BACKGROUND: The optimal management of patients with benign and malignant disease affecting the extrahepatic biliary tract remains unresolved. A retrospective study was undertaken of all surgical biliary bypass procedures performed in one hepatobiliary unit. METHODS: A total of 121 patients treated in a 9-year period and comprising 60 patients with benign disease and 61 with malignant disease were reviewed. RESULTS: There was no significant difference in 30-day mortality rate between patients with benign and malignant disease (2 versus 8 per cent respectively, P = 0.22). There was no significant difference between surgery for benign and malignant disease in early morbidity rate (13 versus 21 per cent respectively, P = 0.36) or late morbidity rate (20 versus 25 per cent, P = 0.70). The median postoperative stay in both groups of patients was 10 days. The median survival of all patients with malignant disease was 7 months, being significantly more favourable for those with cholangio-carcinoma (18 months) than for those with pancreatic carcinoma (6.5 months) (P < 0.01). CONCLUSION: Biliary bypass procedures can be undertaken with acceptable rates of morbidity and mortality, and therefore should be considered in all patients with malignant disease of the extrahepatic biliary tract. If there is evidence of advanced malignancy, or if the patient is unfit for surgical intervention, non-operative procedures are a suitable alternative.

Adolescent↗
PubMed1997

Tumour necrosis factor and inflammatory bowel disease.

BACKGROUND: Tumour necrosis factor (TNF) is a pleiotropic cytokine produced largely by macrophages and T lymphocytes. It has been implicated in the pathogenesis of numerous immunoinflammatory processes. Recently, a number of studies have indicated that anti-TNF antibodies may be of value in the treatment of inflammatory bowel disease. METHODS: The literature is reviewed regarding the role of TNF in the pathogenesis of inflammatory bowel disease and the results of administering TNF inhibitors. RESULTS AND CONCLUSIONS: TNF may have a role in the pathogenesis of inflammatory bowel disease. The effects of TNF inhibitors are complex and incompletely understood. Anti-TNF antibody strategies may have a role in the treatment of acute exacerbations of the disease but are unlikely to be appropriate therapies for long-term management.

Antibodies↗
PubMed1997

Lower limb ischaemia-reperfusion injury alters gastrointestinal structure and function.

BACKGROUND: It has been suggested that bowel permeability is altered following abdominal aortic aneurysm surgery. The effect of ischaemia-reperfusion injury to the lower limb on the morphological structure, neutrophil infiltration and permeability of the bowel was investigated. METHODS: Histological assessment of the bowel was undertaken in five groups of Wistar rats: control, 3 h of bilateral hind limb ischaemia and 3 h of bilateral hind limb ischaemia followed by 1, 2 or 3 h of reperfusion. Using an everted gut sac model and 14C-labelled polyethylene glycol, the effect of ischaemia-reperfusion on small bowel permeability was studied. RESULTS: The small bowel showed a significant decrease in mucosal thickness, villus height and crypt depth in animals subjected to ischaemia followed by 2-hr reperfusion (mean(s.e.m.) 420(15), 217(9) and 163(6) microns respectively) compared with controls (481(11), 245(6) and 195(6) microns) (P < 0.05). Neutrophil count within the lamina propria was similar in the different groups. A significant increase in mean(s.e.m.) 14C-labelled polyethylene glycol translocation was detected in animals subjected to ischaemia-reperfusion compared with controls (760(40) versus 560(27) c.p.m. per ml per h) (P < 0.05). CONCLUSION: These data suggest that reperfusion of acutely ischaemic extremities produces structural and functional changes in the small intestine, although these changes are not associated with increased neutrophil infiltration within the bowel wall.

Animals↗
PubMed1996

Intestinal barrier dysfunction in clinical and experimental obstructive jaundice and its reversal by internal biliary drainage.

Intestinal mucosal barrier function in obstructive jaundice was assessed in an animal model and in patients. The effect of internal biliary drainage in patients was also examined. Bile duct ligation for 1 week in the rat resulted in significant bacterial translocation (in seven of 12 animals following ligation versus none of the shamoperated controls, P < 0.01). Intestinal permeability, measured by the urinary recovery of orally administered polyethylene glycol, was also significantly increased (+66.2 per cent for ligation versus -11.6 per cent for sham, P < 0.01). A prospective study was performed on 33 patients with obstructive jaundice undergoing internal biliary drainage, and results were compared with those in six non-jaundiced patients undergoing laparotomy or endoscopic retrograde cholangiopancreatography and in 11 health volunteers. The lactulose: mannitol ratio was used as an intestinal permeability index. Mean(s.e.m.) intestinal permeability assessed before operation was significantly increased in jaundiced patients compared with control patients (0.050(0.010) versus 0.016(0.003), P < 0.005). The mean(s.e.m.) lactulose: mannitol ratio in the healthy volunteers was 0.020(0.003), which was similar to that in control patients. In the jaundiced group of patients the intestinal permeability index fell to within normal levels after 28 days of internal biliary drainage (0.050 before operation versus 0.021 at 28 days, P < 0.02). These data indicate that intestinal barrier function is impaired in obstructive jaundice and that this impairment is reversed by return of bile to the gastrointestinal tract.

Animals↗
PubMed1996

Mortality following lower limb ischemia-reperfusion: a systemic inflammatory response?

Restoration of blood flow to an acutely ischemic lower limb may paradoxically result in systemic complications and unexpected mortality. It has been suggested that lower limb ischemia reperfusion alters gut permeability. In this study, using a rat model, we determined the effect of acute lower limb ischemia-reperfusion on mortality rate, bowel morphology, and circulating concentrations of endotoxin and the proinflammatory cytokine interleukin-6. Survival rate was compared in two groups of adult Wistar rats: (1) control group (n = 10); and (2) animals subjected to 3 hours of bilateral hind limb ischemia followed by reperfusion (n = 10). Both groups were observed under standard conditions for 4 days. In a second experiment three groups of animals were studied: (I) control (n = 12); (II) 3 hours of bilateral hind limb ischemia alone (n = 12); and (III) 3 hours of bilateral hind limb ischemia followed by 2 hours of reperfusion (n = 12). Animals subjected to bilateral hind limb ischemia followed by reperfusion had a significantly higher mortality rate (70%) than controls (0%) (p < 0.005). Morphometric assessment of the small bowel showed a significant decrease in mean mucosal thickness in the ischemia-reperfusion group compared with that in the group of controls and the ischemia-alone group (p < 0.05). Bilateral hind limb ischemia followed by reperfusion was associated with significantly increased plasma concentrations of endotoxin (p < 0. 05) and interleukin-6 (p < 0.0001) compared with that of controls and ischemia alone. These results indicate that reperfusion of the acutely ischemic lower limb is accompanied by structural changes in the gut mucosa associated with increased systemic endotoxin concentrations and cytokine activation. Mortality following reperfusion of the acutely ischemic limb may be related to a systemic inflammatory response triggered by endotoxin of gut origin.

Analysis of Variance↗
PubMed1996

Effect of supplemental L-arginine in a chemical-induced model of colorectal cancer.

L-Arginine inhibits the development of spontaneous, transplantable solid tumors and chemically induced mammary tumors. The aim of the present study was to investigate the effect of l-arginine on chemically induced colorectal cancer in male Wistar rats. Colorectal cancer was induced in all animals by weekly subcutaneous injections of the colonic procarcinogen 1,2-dimethylhydrazine (DMH) at a dosage of 20 mg/kg body weight. Arginine was given in a 1% solution of drinking water. Group I was the DMH control; group II, arginine for 22 weeks; group III, arginine for the first 10 weeks only. Lymphocyte function was evaluated by measuring the thymic lymphocyte proliferative response to the T cell mitogen phytohemagglutinin. The results show that tumor incidence and tumor burden (tumors/rat and tumors/tumor-bearing rat) were significantly reduced in both groups of animals receiving arginine compared to DMH controls (p < 0.05). The tumor areas and volumes were also reduced in both arginine groups (p < 0.05). Thymic lymphocyte stimulation indices were significantly increased by arginine supplementation (p < 0.05). These results would be in keeping with the reduction in colorectal tumor production due to a "nonspecific" stimulation of the host immune system by L-arginine.

1,2-Dimethylhydrazine↗
PubMed1996

Modulation of TNF alpha and IL-6 in a peritonitis model using pentoxifylline.

Sepsis leads to release of reactants that play an important role in the development of multiple organ failure. The kinetics of two early mediators of the response to sepsis, tumour necrosis factor (TNF alpha) and interleukin 6 (IL-6), and their modulation with pentoxifylline (PTF), were investigated. An established and clinically relevant animal model was employed, and sepsis was induced by cecal ligation and puncture (CLP) in Wistar rats. Six hours after the operation, there was an increase in IL-6 in all animals, which declined toward normal by 18 hours. This early phase of IL-6 production was not influenced by PTF. TNF alpha and IL-6 were significantly higher in the CLP group than in the animals treated with PTF at 24 hours. The blood pressure of the CLP group at 24 hours was significantly lower than that of the shams, and this decrease was not influenced by PTF. This decline in blood pressure may have been the stimulus to TNF production and the second phase of IL-6 production, which appeared to be inhibited by PTF. Pentoxifylline appears to attenuate systemic cytokine production in this model and may have a role in the management of clinical sepsis.

Animals↗
PubMed1996

The effect of air fluidised bed therapy on hypermetabolism in intensive care unit patients.

Major trauma is associated with a hypermetabolic (increased resting energy expenditure) and hypercatabolic (negative nitrogen balance) response. Studies have suggested that nursing injured patients at higher temperatures reduces the metabolic response (Ryan & Clague 1990). In this study the energy expenditure and urinary nitrogen excretion of major trauma patients was examined when nursing them on an air-fluidised bed at 32 degrees C using a crossover study design. Patients were randomised into two groups. Group A patients (n = 8) remained on a standard intensive care unit bed at an environmental temperature of 22 degrees C while Group B patients (n = 6) were placed on an air-fluidised bed operating at 32 degrees C. On days 4 and 5 after injury, energy expenditure and urinary nitrogen excretion were measured. On day 6, Group A patients transferred to an air-fluidised bed and Group B patients to a standard bed. On days 7 and 8, energy expenditure and urinary nitrogen excretion were again measured. Within group comparisons of energy expenditure and urinary nitrogen excretion were made for days 3 and 4 (period 1) and days 7 and 8 (period 2). In both groups, mean energy expenditure was significantly increased in the second period irrespective of whether air-fluidised bed therapy preceded or followed a period on a standard bed. We concluded that nursing intensive care patients on an air-fluidised bed at 32 degrees C did not influence energy expenditure or urinary nitrogen.

Adult↗
PubMed1996

The generation of byproducts of lipid peroxidation following carotid endarterectomy.

The aim of this study was to determine whether free radical-induced lipid peroxidation occurs following transient carotid clamping. Jugular vein plasma levels of malondialdehyde (MDA) and diene conjugates (DC) were estimated in 24 patients undergoing carotid endarterectomy, at the beginning of the operation (To), just prior to clamping the carotid artery before the shunt was removed for closure of the arteriotomy (Ts), and at 30 (T30), 60 (T60), 120 (T120), 180 (T180) and 300 (T300) seconds after the clamps were released. Carotid clamp times were recorded. Significant elevations in the concentrations of both MDA and DC were observed at T60 after clamp release (MDA = 559 +/- 64 pmol/ml, DC = 428 +/- 32 units/ml), in comparison to concentrations at To (MDA = 408 +/- 34 pmol/ml, p < 0.01; DC = 374 +/- 28 units/ml, p < 0.05), returning to baseline at T300. There was a significant correlation between the percentage rise in MDA concentration and the duration of clamp-induced ischaemia (r = 0.45, p = 0.03). The significance of this burst of MDA and DC is unclear especially as the one patient who sustained a postoperative neurological deficit displayed no rise in the concentration of either. If this rise is related to free radical generation following ischaemia-reperfusion injury it may play an important role in influencing the clinical outcome in the patients.

Aged↗
PubMed1996

Neuron-specific enolase as an aid to outcome prediction in head injury.

A statistically significant elevation was observed in serum and CSF neuron-specific enolase (NSE) levels in patients with major head injury, relative to control individuals. No correlation was noted between serum NSE and either APACHE II, Injury Severity Score (ISS), Glasgow Outcome Score (GOS) or Glasgow Coma Scale (GCS). A significant correlation was noted between CSF NSE levels and GCS, but not between CSF NSE and APACHE II, ISS or GOS. Of the patients with major head injury, 100% had NSE CSF levels above the normal level, while 47% had elevated serum NSE levels. In nine patients with major head injury, changes in CSF levels reflected changes in serum NSE levels. In all nine patients, serum NSE decreased to reach normal values, regardless of the outcome as predicted by the GOS. Therefore, while NSE would appear to be a marker of neuronal cell damage, other markers are also essential.

Adult↗
PubMed1996

Biliary decompression promotes Kupffer cell recovery in obstructive jaundice.

BACKGROUND: Jaundiced patients undergoing surgical procedures have an increased risk of Gram negative sepsis with potential morbidity and mortality. Depressed Kupffer cell clearance capacity (KCCC) predisposes jaundiced patients to endotoxaemia and its sequelae. Biliary decompression remains the main therapeutic strategy in obstructive jaundice. AIMS: This study investigates the efficacy of internal (ID) and external biliary drainage (ED) on KCCC in an experimental model of extrahepatic biliary obstruction. METHODS: Adult male Wistar rats (250-300 g) were assigned to one of six groups: sham operated, where the bile duct was mobilised but not divided; bile duct ligation (BDL) for three weeks, and sham operated or BDL for three weeks followed by a second laparotomy and further 21 days of ID or ED, by way of choledochoduodenostomy or choledochovesical fistula respectively. KCCC was measured using an isolated hepatic perfusion technique with FITC labelled latex particles (0.75 mu) as the test probe. Plasma was assayed for bilirubin, endotoxin, and anticore glycolipid antibody (ACGA) concentrations. RESULTS: Jaundiced rats had reduced KCCC (p < 0.001), increased concentrations of ACGA (p < 0.001), and endotoxin (p < 0.001) compared with controls. Biliary drainage for three weeks produced a recovery in KCCC and normalisation of endotoxin and ACGA concentrations, however, external drainage was less effective than ID (p < 0.01). CONCLUSIONS: These data support the hypothesis that endotoxaemia and its mediated effects are integral in the pathophysiology of jaundice. Furthermore, a short period of internal biliary drainage is a useful therapeutic strategy in restoring Kupffer cell function and negating systemic endotoxaemia and consequent complications in biliary obstruction.

Animals↗