Search PubMed⌕ Search

Biomedical subjects

B J Rowlands

Publications and source records attributed to B J Rowlands.

At least 73 records · Page 4Linked to original sources
PubMed1996

Role of the gut in the pathophysiology of extrahepatic biliary obstruction.

BACKGROUND: Gram negative septic events are the commonest source of morbidity and mortality as a result of surgery in jaundiced patients. The large intestine provides the major source of Gram negative bacteria in mammals and is implicated in the pathogenesis of systemic endotoxaemia in obstructive jaundice. Bile salts have an important part in maintaining indigenous microecological homeostasis through their emulsifying properties. AIMS: The aim was to investigate the effects of biliary obstruction and isolated external biliary diversion on gastro-intestinal structure and caecal bacterial flora in relation to bacterial translocation. METHOD: Six groups of adult male Wistar rats were studied (no operation, sham operated, and bile duct ligated (BDL) for one and three weeks and a choledocho-vesical fistula (CDVF) for one week). At the end of the study period plasma was assayed for evidence of endotoxaemia and the animals were tested for bacterial translocation to the mesenteric lymph node complex (MLNC), liver, lungs, and spleen. Quantitative and qualitative bacteriological studies were performed on the caecal contents and segments of colon and terminal ileum were washed and prepared for histological assessment. RESULTS: Bacterial translocation was significantly increased in the BDL1 (68.8%) and BDL3 (60%) groups compared with the sham1 (6.3%), sham3 (9.1%), No operation (0%), and CDVF1 (16.7%) groups. Although translocation was more pronounced in the BDL1 group, this was almost exclusively to the MLNC compared with the more widespread translocation to other organs in the BDL3 group. The BDL3 group was the only group with significantly raised concentrations of endotoxin and anticore glycolipid. The caecal Gram negative aerobic counts were significantly increased in the BDL1 and CDVF1 groups compared with all other groups. There was evidence of structural abnormalities in the terminal ileum of rats jaundiced for three weeks, but not in the other groups. CONCLUSIONS: Biliary obstruction for one and three weeks promotes bacterial translocation although the mechanisms may be different. Absence of intralumenal bile results in a significant but self limiting increase in the Gram negative aerobic population, which may account for translocation in the early stages of biliary obstruction. As the duration of biliary obstruction increases systemic endotoxaemia is a consistent feature which, combined with factors such as immunological depression and physical disruption of gut barrier function, may promote bacterial translocation perpetuating systemic sepsis.

Animals↗
PubMed1996

Transduodenal sphincteroplasty and transampullary septectomy for papillary stenosis.

Twenty patients received transduodenal sphincteroplasty and transampullary septectomy between 1987 and 1993. Seven patients had post-cholecystectomy pain which was much improved or abolished in 5 of 7 patients at a mean follow-up of 4 years and 5 months. Four of five patients with chronic pancreatitis were improved at 3 years and 2 months. Three of five patients with recurrent acute pancreatitis were improved at 4 years and 5 months. One of three patients with chronic abdominal pain of hepatobiliary origin was improved at 3 years. Transduodenal sphincteroplasty and transampullary septectomy can relieve pain in patients with post-cholecystectomy pain, recurrent acute pancreatitis, chronic pancreatitis, and chronic abdominal pain of hepatobiliary origin, presumably by improving drainage of the obstructed ducts.

Abdominal Pain↗
PubMed1996

Serum bile acids and ursodeoxycholic acid treatment in cystic fibrosis-related liver disease.

Increased circulating levels of hepatotoxic bile acids may contribute to the cholestasis characteristic of cystic fibrosis-related liver disease. The aims of this study were to compare serum bile acid profiles in patients with cystic fibrosis with and without liver disease, and to evaluate the effect of treatment with ursodeoxycholic acid, a non-hepatotoxic bile acid, on liver biochemistry and serum bile acids in patients with cystic fibrosis-related liver disease. Fasting and postprandial serum bile acid levels were analysed in 15 patients (nine males; median age 18 years) with cystic fibrosis-related liver disease and compared with serum bile acid levels in 18 cystic fibrosis patients (12 males; median age 22 years) without liver disease and 10 control subjects. Fasting and postprandial serum levels of primary and secondary serum bile acids were analysed using high-performance liquid chromatography. Liver biochemistry and serum bile acids were measured in six cystic fibrosis patients with liver disease before and 6 months after treatment with ursodeoxycholic acid 20 mg/kg/day and compared with six control patients with cystic fibrosis-related liver disease. Total fasting and postprandial serum bile acid levels were significantly (P < 0.01) elevated in patients with liver disease compared to those without liver disease and controls. The fasting glycine conjugates of cholic acid, chenodeoxycholic acid and deoxycholic acid, and the fasting and postprandial taurine conjugates of cholic acid and chenodeoxycholic acid were significantly (P < 0.05) elevated in liver disease patients compared to patients without liver disease and controls. After 6 months' treatment with ursodeoxycholic acid, although the serum was significantly saturated with ursodeoxycholic acid and significant improvements in liver biochemistry were observed in the treatment group, there was no significant reduction in the levels of individual serum bile acids. Although circulating levels of potentially hepatotoxic serum bile acids are elevated in patients with cystic fibrosis-related liver disease, improvements in liver biochemistry associated with ursodeoxycholic acid treatment cannot be attributed solely to alterations in levels of endogenous bile acids.

Adolescent↗
PubMed1996

Lipid peroxidation assessment of free radical production following release of obstructive uropathy.

PURPOSE: To identify if free radicals were released following relief of ureteric obstruction. MATERIALS AND METHODS: Free radical production was assessed by a high performance liquid chromatography assay of malondialdehyde (MDA) in a 24-hour complete unilateral ureteric obstruction model in Wistar rats. RESULTS: In the first experiment, a rise greater than 20% above prerelease levels in renal venous malondialdehyde levels was observed at 8, 15, 22, and 30 minutes following release. At 45 and 60 minutes, levels were similar to the prerelease levels. In the second experiment, renal venous samples taken before release and at 10 and 20 minutes after release in control and obstructed groups (n = 7) identified a significant difference (T = 10 minutes p = 0.006 and T = 20 minutes p = 0.045). A significant MDA rise following release occurred only in the obstructed group (obstruction group; MDA level T = 0 min. 1.01 mumol/l. +/- 0.13, T = 10 min. 2.12 mumol/l. +/- 0.3 p = 0.016, T = 20 min. 2.09 mumol/l. +/- 0.28 p = 0.016. CONTROL GROUP: T = 0 min. 1.13 mumol/l. +/- 0.23, T = 10 min. 1.05 mumol/l. +/- 0.18 p = 0.95, T = 20 min. 1.23 mumol/l. +/- 0.19 p = 0.67). In the third experiment, an attempt was made to block free radical release with allopurinol. No statistical difference between the control and obstructed groups with allopurinol was noted at 20 minutes after release. A Kruskal Wallace two-way analysis identified a significant difference between experiments two and three at both time periods (p = 0.049). CONCLUSION: This study suggests, for the first time, that free radicals are released after relief of ureteric obstruction and that this release is partially attenuated by allopurinol pretreatment.

Animals↗
PubMed1996

Bacterial translocation and gut microflora in obstructive jaundice.

Bacterial translocation from the gut is implicated in the pathophysiology of complications associated with obstructive jaundice. Absence of intraluminal bile salts and their antiendotoxic effects may result in overgrowth of bacteria, promoting bacterial translocation. The large bowel is the largest source of gram negative bacteria but the small bowel is more permeable. This study investigated the effect of obstructive jaundice on bacterial translocation and on the indigenous luminal microflora at 3 sites in the gastrointestinal tract. Significant bacterial translocation was demonstrated following 7 d of bile duct ligation compared with control or sham operated groups. A qualitative disturbance of the caecal indigenous microflora was demonstrated in jaundiced rats. There was no 'site-to-site' variation in the indigenous microflora at the 3 intestinal sites studied. We conclude that experimental obstructive jaundice for 1 wk promotes bacterial translocation without significant quantitative disturbance of the intestinal microflora in the small intestinal or caecum.

Animals↗
PubMed1995

Lactulose as an antiendotoxin in experimental colitis.

The efficacy of lactulose as an antiendotoxin was studied and the effect of lactulose or colistin on faecal flora was investigated in a hapten-induced rat model of colitis. Enteral administration of lactulose to rats with colitis was associated with a significant reduction in the systemic concentration of endotoxin (median (range) 5.4 (0-19.9) versus 23.7 (0-145.0) pg/ml in colitic rats treated with water; 4.6 (0-10.8) pg/ml in healthy animals). Enteral administration of colistin significantly reduced the faecal count of aerobic Gram-negative bacilli (median (range) 2.84 (1.40-8.43) versus 8.26 (4.50-10.40) log10 colony-forming units per g faeces after treatment with water) but not the faecal load of endotoxin. Patients with inflammatory bowel disease may benefit from enteral treatment with lactulose to prevent systemic endotoxaemia and/or with colistin to modify enteric bacteria.

Animals↗
PubMed1995

Renal dysfunction in obstructive jaundice.

The association between renal dysfunction and obstructive jaundice is well established. Despite a substantial number of clinical reviews and prospective studies, the exact incidence and extent of the problem has not been determined accurately. Various pathogenic mechanisms and therapeutic strategies have been proposed but renal dysfunction remains a persistent problem in hepatobiliary practice. The intention of this review is to determine the current extent of the problem, outline the proposed pathophysiological mechanisms and assess the current therapeutic options.

Acute Kidney Injury↗
PubMed1995

Effect of low-dose dopamine on sigmoid colonic intramucosal pH in patients undergoing elective abdominal aortic aneurysm repair.

The effect of low-dose dopamine administration on intramucosal pH (pHi) of the sigmoid colon and on postoperative function of various organs in patients undergoing elective abdominal aortic aneurysm repair was examined. Nineteen patients were randomized to two groups; nine received dopamine at a rate of 3 micrograms per kg per min for 24 h from induction of anaesthesia and ten control patients received fluids without dopamine. pHi was measured with a silicone tonometer and daily samples of blood were taken for measurement of liver transaminase activity, arterial oxygen saturation and creatinine concentration. Mean(s.e.m.) pHi fell to a significantly lower minimum value in those receiving dopamine compared with control patients (6.86(0.10) versus 7.11(0.08), P < 0.05). Five of the nine patients given dopamine developed intramucosal acidosis compared with only one of the ten control patients (P = 0.06). After operation the mean(s.e.m.) aspartate transaminase concentration in patients given dopamine rose from 33(2) to 80(17) units/l (P < 0.01); in control patients it rose from 32(3) to 59(16) units/l (P = 0.054). No differences between the groups was observed in the postoperative ratio of arterial oxygen saturation to inspired oxygen fraction or creatinine concentrations. These results indicate that dopamine has no beneficial effect on bowel mucosal oxygenation and function of the various organs in patients undergoing aortic aneurysm repair.

Aged↗
PubMed1995

Manipulation of the L-arginine-nitric oxide pathway in experimental colitis.

The role of the L-arginine-nitric oxide pathway in the pathogenesis of colonic inflammation was assessed using L-arginine and its competitive analogue N omega-nitro-L-arginine methyl ester (L-NAME) in a rat model of colitis. In the first study oral L-arginine 2 per cent (control: 3.4 per cent L-glycine) was administered with and without L-NAME 100 mg/l. Orally administered L-arginine increased colonic inflammation (P = 0.004) and decreased thymic weight (P = 0.0007). Addition of L-NAME reduced the colonic inflammation and prevented loss of body-weight (P < 0.04). In the second study L-NAME was administered orally in concentrations of 100, 200 and 500 mg/l (control: no L-NAME). L-NAME 500 mg/l reduced colonic inflammation and increased thymic weight and body-weight (P < 0.01). Thymic weight and body-weight correlated positively with the concentration of L-NAME administered orally (rs > or = 0.3, P = 0.04). L-NAME l g/l was administered topically as an enema (control: suspension agent). Topical L-NAME reduced colonic inflammation and increased thymic weight (P < 0.05). These results suggest that the L-arginine-nitric oxide pathway mediates colonic inflammation in this model.

Administration, Oral↗
PubMed1995

Endotoxaemia and cytokine production in experimental colitis.

Systemic endotoxaemia is a well recognized feature of inflammatory bowel disease but its pathogenic role remains uncertain. This study examined plasma endotoxin and cytokine concentrations and the acute-phase protein response in a hapten-induced model of experimental colitis. On days 2, 8 and 14 after induction of colitis with trinitrobenzenesulphonic acid in ethanol (TNBS-E), plasma endotoxin, immunoglobulin (Ig) G and IgM endotoxin-core antibody (EndoCAb), tumour necrosis factor (TNF), interleukin (IL) 6 and alpha 2-macroglobulin (alpha 2M) concentrations and colon macroscopic inflammation score were determined. At all time points there was significant colonic inflammation when compared with control values (P < 0.0001). Animals treated with TNBS-E had raised concentrations of endotoxin at all time points (P < 0.04). In TNBS-E-treated animals EndoCAb concentrations were reduced on day 2 (P < 0.0001) and later increased. There were increases in IL-6 and alpha 2M concentrations in TNBS-E-treated animals but no significant change in TNF concentrations. Endotoxin concentrations correlated with macroscopic inflammation score, IL-6 and alpha 2M concentrations. There was a less consistent correlation between EndoCAb concentrations and these parameters. These results suggest that endotoxin is a mediator of the systemic response in this model of experimental colitis.

Animals↗
PubMed1995

Topical glutamine therapy in experimental inflammatory bowel disease.

This study investigated the effects of glutamine and steroid enemas on disease activity in an animal model of colitis. Colitis was induced in male Wistar rats by intracolonic instillation of 30 mg trinitrobenzenesulphonic acid in 50% ethanol (TNBS/E). Controls were given an isovolumetric bolus of normal saline. After 24 h, animals were randomised to receive enemas (1 mL twice daily) of prednisolone (200 mg/L), or L-glutamine (500 g/L) or the suspending agent (placebo). On day 8, the colon was weighed and the degree of inflammation assessed using a colon macroscopic score (CMS). Thymic weight, splenic weight, percentage gain in body weight (%GBW), food intake, plasma interleukin-6 (IL6) and plasma alpha(2)-macroglobulin (alpha(2)M) were also determined. There was a significant increase in CMS, colon weight, splenic weight, IL6 and alpha(2)M in TNBS/E animals compared to controls (P< 0.01). There was also a significant decrease in %GBW, food intake and thymic weight in TNBS/E animals (P< 0.01). The therapeutic enema of prednisolone reduced colonic inflammation (CMS, colon weight), improved thymic weight, %GBW and food intake, and reduced plasma IL6 concentrations (P< 0.05). In contrast administration of glutamine enemas was associated with an exaggerated acute phase protein (alpha(2)M) response (P< 0.05) and failed to improve the colonic and systemic inflammatory response in this experimental model of colitis.

Journal Article↗
PubMed1995

Significance of systemic endotoxaemia in inflammatory bowel disease.

Quantitative and qualitative disturbances in faecal flora suggest a role for enteric bacteria and their products in the pathogenesis of inflammatory bowel disease (IBD). This study investigated the hypothesis that systemically circulating endotoxins are of pathogenic significance in IBD by measuring antibody, cytokine, and acute phase protein responses. Systemic endotoxaemia was found in 88% patients with ulcerative colitis (n = 25) and 94% with Crohn's disease (n = 31) during clinical relapse. Systemic endotoxaemia correlated positively with anatomic extent and clinical activity of ulcerative colitis. Circulating tumour necrosis factor (TNF) was detected in 40% of patients with ulcerative colitis and 45% with Crohn's disease. Plasma TNF concentrations correlated with clinical and laboratory measures of disease activity and were associated with a surgical outcome to the disease episode. Plasma soluble TNF receptor p55 concentration correlated positively with disease activity and endotoxin core antibody concentrations. Plasma IgG endotoxin core antibody concentrations were significantly increased in patients with Crohn's disease and correlated with systemic endotoxaemia. The presence of systemic endotoxaemia, its correlation with disease activity, disease extent, and endotoxin core antibody concentration and the detection of circulating TNF and soluble TNF receptors all support a pathogenic role for endotoxins in IBD.

Adolescent↗
PubMed1995

Colitis and colonic mucosal barrier dysfunction.

Trauma, infection, neoplasia, and inflammation can all disrupt the intact intestinal mucosal barrier to intraluminal bacteria and bacterial antigens. This study investigated the relation between colonic inflammation and colonic mucosal barrier function in three experimental models of colitis. There were significantly increased systemic endotoxin concentrations in rats with acetic acid (7.5 (1.7-119.5) pg/ml), ethanol (13.7 (0-111.2) pg/ml), and hapten induced (14.4 (5-31.1) pg/ml) colitis compared with saline controls (3.3 (0-13.7) pg/ml). Data expressed as median (range). There were significant correlations between the systemic endotoxin concentration and both the severity of colitis and of illness in acetic acid induced colitis. A significant increase in colonic permeability to 14C-polyethylene glycol was shown in rats with acetic acid (3.42 (1.36-5.63)%) and hapten induced colitis (2.86 (1.03-8.10)%) compared with saline controls (1.20 (0.67-1.36)%). Data expressed as median (range) of percentage of the intracolonic bolus excreted in urine. There was a significant positive correlation between the severity of colitis and % colonic permeability to 14C-polyethylene glycol. This and other studies provide evidence that mucosal barrier dysfunction is a feature of colitis irrespective of aetiology or species. Such barrier dysfunction may be responsible for the systemic inflammatory response and complications seen in patients with inflammatory bowel disease.

Acetates↗