Biomedical subjects
B J Rowlands
Publications and source records attributed to B J Rowlands.
Hepatic abscess formation following embolisation of a carcinoid metastasis.
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Prospective study of postoperative renal function in obstructive jaundice and the effect of perioperative dopamine.
A prospective study was undertaken to assess postoperative renal dysfunction in patients with obstructive jaundice and to determine the effectiveness of dopamine in reducing its incidence. A total of 23 patients undergoing surgical relief of obstructive jaundice (serum bilirubin level above 100 mumol l-1) were randomized into two groups. Those in the control group (n = 10) received 3 litres 5 per cent dextrose intravenously during the 24 h before surgery plus a bolus of intravenous frusemide 1 mg kg-1 at induction of anaesthesia. The second group (n = 13) received a similar fluid and frusemide regimen plus an infusion of dopamine 3 micrograms kg-1 min-1 starting at induction of anaesthesia and continuing for 48 h after surgery. Postoperative oliguria occurred in two of the ten patients in the control group and in three of the 13 given dopamine (P = 0.74). No patient developed acute renal failure. There was no significant difference in mean levels of serum bilirubin, urea and creatinine, creatinine clearance and 24-h urinary output, on the day before and on days 1-5 after operation, between the two groups. It is concluded that, with careful preoperative resuscitation and control of fluid and electrolyte balance, the incidence of postoperative renal dysfunction in patients with obstructive jaundice is not as high as in some previous studies and is unaltered by administration of perioperative low-dose dopamine.
Bowel ischaemia and organ impairment in elective abdominal aortic aneurysm repair.
In 30 patients undergoing elective repair of abdominal aortic aneurysm the intramucosal pH (pHi) of the sigmoid colon was measured. Blood for endotoxin assay was taken at intervals before, during and after surgery. Daily measurements were made of liver transaminase activity and of arterial partial pressure of oxygen (PaO2). The mean (s.e.m.) peak systemic endotoxin concentration in those who developed intramucosal acidosis (pHi below 7.00) was 90(14) pg/ml, compared with 42(5) pg/ml in those who did not (P < 0.01). In the 14 patients whose pHi fell below 7.00, the mean (s.e.m.) postoperative rise in aspartate transaminase activity was 346(74) per cent, compared with 181(20) per cent in those whose pHi remained above this level (P < 0.05). The mean (s.e.m.) postoperative ratio of PaO2 to the fraction of inspired oxygen was 177(11) mmHg in those with intramucosal acidosis, compared with 260(24) mmHg in those whose pHi remained above 7.00 (P < 0.01). These results demonstrate a relationship between bowel ischaemia, endotoxaemia and organ impairment following elective aneurysm repair.
Modulation of immune function and weight loss by L-arginine in obstructive jaundice in the rat.
Jaundiced surgical patients have a high incidence of postoperative complications. Many causative factors have been identified including cachexia and immune suppression. The amino acid L-arginine has anabolic and immunostimulatory properties. It was hypothesized that dietary supplementation with L-arginine would diminish the weight loss and immune suppression of obstructive jaundice. Sixteen male Wistar rats rendered jaundiced by bile duct ligation were allocated to two groups. The test group (n = 8) received drinking water supplemented with 1.8 percent L-arginine ad libitum and the control group (n = 8) received a solution of isonitrogenous glycine. Both groups had free access to standard chow. Body-weight, and fluid and food intake were recorded. After 21 days, delayed-type hypersensitivity to 2,4-dinitrofluorobenzene was assessed. Animals receiving L-arginine consumed more food than controls (mean(s.e.m.) 414(16) versus 360(13) g, P < 0.05) and lost less weight (mean(s.e.m.) proportion of initial body-weight lost 7.8(1.2) versus 14.8(1.4) percent, P < 0.05). The delayed-type hypersensitivity response was significantly greater in rats receiving L-arginine (mean(s.e.m.) increase in ear thickness 23.9(2.7) versus 9.4(2.1) percent, P < 0.05). In this animal model of obstructive jaundice dietary supplementation with L-arginine diminished both weight loss and immune suppression.
The role of mast cell activation in cholestatic pruritus.
Jaundiced patients experience intense pruritus, the pathophysiology of which is unclear. In this study, blood histamine concentrations, skin mast cell counts and intracellular histamine concentrations in peritoneal mast cells were examined in an experimental model of biliary obstruction. Three weeks after bile duct ligation (BDL), total blood histamine concentrations were significantly elevated compared with those from control animals (p < 0.0001). Skin mast cell counts were increased (p < 0.05) and peritoneal mast cell histamine content decreased (p < 0.05) in jaundiced animals. These results demonstrate that mast cells degranulate in biliary obstruction with consequent release of histamine into the systemic circulation. This may contribute to cholestatic pruritus. These data may have significant pharmacological implications in patients with obstructive jaundice.
Pentoxifylline improves intracellular electrolytes in sepsis.
Sepsis is associated with a generalised membrane dysfunction leading to an increase in intracellular sodium, chloride, and water. The decrease in extracellular water is thought to act as a nonosmotic stimulus to the secretion of antidiuretic hormone. The resultant hyponatraemia is associated with increased surgical morbidity and mortality. Treatment aimed at improving intracellular electrolytes may improve surgical morbidity and mortality. An animal model of peritonitis was used to evaluate the effect of pentoxifylline. Previously, this dimethyl xanthine derivative was shown to stabilise the cell membrane. Administration of pentoxifylline significantly lowered intracellular sodium and chloride, particularly when given after caecal ligation and puncture. This may have clinical implications in the treatment and prevention of hyponatraemia.
Reduction of free radical generation minimises lower limb swelling following femoropopliteal bypass surgery.
Oxygen-derived free radicals have been implicated as contributors to the development of lower limb oedema observed after femoropopliteal bypass grafting. This study investigates the occurrence of free radical-induced lipid peroxidation after this operation and the possible effects of allopurinol (xanthine oxidase inhibitor) in reducing free radical injury in order to minimise lower leg oedema. Twenty-nine patients undergoing femoropopliteal bypass surgery were randomised in a double blind fashion into two groups; those in one were given allopurinol 200 mg orally (n = 15) at 24 h and 2 h preoperatively and again at 24 h postoperatively, while those in the second group received a placebo (n = 14). Daily lower limb volume was calculated to assess swelling. Blood samples were taken from the femoral vein for measurements of malondialdehyde (MDA), an end product of lipid peroxidation, before the application of the femoral artery clamp, just prior to and immediately after clamp release, and at 20 minute intervals thereafter for 1 hour. The increase in lower limb volume in the placebo group was almost twice (8.9 +/- 1.6%) that of the allopurinol group (4.6 +/- 1%; p = 0.02). Six out of the 14 patients receiving placebo suffered swelling of 10% or more of original lower limb volume in comparison to only one out of 15 in those given allopurinol (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Are bioavailable glutamine and sensitivity to hydrochloric acid DNA denaturation important colorectal tumour characteristics?
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Measuring Kupffer cell clearance capacity (KCCC) using an isolated hepatic perfusion technique.
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The role of IL-6 in the pathophysiology of jaundice.
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Predictive value of soluble immunological mediators in neonatal infection.
1. Infection in the neonatal period is difficult to diagnose and is a significant cause of morbidity and mortality in preterm infants. 2. We investigated prospectively the predictive value of plasma measurement of bacterial endotoxin (lipopolysaccharide), tumour necrosis factor-alpha, interleukin-6, interleukin-8, intercellular adhesion molecule-1 and C-reactive protein in 60 consecutive newborn infants suspected of having neonatal infection. Plasma samples were taken at the time of acute clinical deterioration. Sixty-two cord blood samples were studied as controls taken at elective Caesarean section. 3. Forty-three infants had confirmed infections, 25 with positive blood cultures. Tumour necrosis factor-alpha and bacterial endotoxin levels were not significantly elevated over controls, whereas interleukin-6, interleukin-8 and intercellular adhesion molecule-1 levels were all significantly increased in the infected group compared with controls (all P < 0.001). 4. Increased plasma intercellular adhesion molecule-1 levels were a highly sensitive (88%) indicator of clinical infection and were independent of C-reactive protein. Use of these two assays in combination improved the diagnostic sensitivity to 95% and gave a negative predictive value of 97%. addition of interleukin-6 or interleukin-8 measurements failed to further significantly enhance the prediction of infection. 5. Measurement of intercellular adhesion molecule-1 level may have a clinical role in rapidly confirming, or predicting, the likely diagnosis in cases of suspected neonatal infection.
Class II major histocompatibility complex antigen expression on peripheral blood monocytes in patients with inflammatory bowel disease.
Macrophage major histocompatibility complex (MHC) class II antigen expression is associated with defective antigen presentation to T lymphocytes in animals and is predictive of patient outcome after major trauma or sepsis. In this study, class II antigen (HLA-DR and DQ) expression on peripheral blood monocytes was investigated in patients with inflammatory bowel disease in relation to disease activity and outcome. The percentage positivity and fluorescent intensity of expression of HLA-DR and DQ antigens on monocytes were determined in whole blood samples using dual colour immunofluorescence labelling and flow cytometry. Disease activity was assessed using clinical and laboratory indices. There was no significant difference in percentage positivity or fluorescent intensity of class II antigen expression between patients with Crohn's disease, those with ulcerative colitis, and healthy volunteers. The percentage of monocytes displaying HLA-DR positivity was significantly decreased in patients with active ulcerative colitis (active %: 49.5 (5.6); inactive %: 78.9 (6.9); p = 0.01). Data expressed as mean (SEM). In patients requiring surgical resection of diseased bowel, the percentage of monocytes displaying HLA-DR positivity (51.9 (4.0) %) was significantly reduced compared with patients receiving medical treatment alone (81.1 (3.5) %; p < 0.001). Reduced monocyte HLA-DR expression is therefore associated with disease activity and seems to predict outcome in patients with inflammatory bowel disease.
The presence of tumour necrosis factor in CSF and plasma after severe head injury.
In a cohort of victims of traumatic brain injury, 18 out of 50 patients had a plasma tumour necrosis factor (TNF) concentration above 2 pg/ml within 24 h of injury (mean 12.19, SD 45.96 pg/ml). Twenty-six had CSF samples available of which 17 demonstrated TNF concentrations above 1 pg/ml (mean 3.98, SD 3.61 pg/ml). We conclude that traumatized brain parenchyma is a significant source of TNF activity and implicate the cytokine in cellular metabolic derangements following head injury.
Enteral and parenteral anti-endotoxin treatment in experimental colitis.
Systemic endotoxemia has been described in ulcerative colitis and Crohn's disease and shown to correlate positively with disease activity and the extent of intestinal ulceration. This study evaluated the efficacy of antibiotic and anti-endotoxic treatment in reducing systemic endotoxemia in a hapten-induced rat model of colitis. Enteral administration of paromomycin was associated with a significant reduction in systemic endotoxin concentrations (7.4 +/- 1.2 pg/ml) when compared with controls (39.8 +/- 12.6 pg/ml; p = 0.032). Intravenous injection of taurolidine was also found to significantly reduce systemic endotoxemia (3.1 +/- 1.3 pg/ml) in comparison with controls receiving saline injection (17.5 +/- 4.2 pg/ml; p = 0.008). Enteral neomycin, parenteral polymyxin or metronidazole and cefuroxime were ineffective anti-endotoxin treatments in this model. Enteral paromomycin or parenteral tauro-lidine therapy are potential methods of preventing and treating systemic endotoxemia in patients with inflammatory bowel disease.
Pentoxifylline modulates cytokine responses in a sepsis model.
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Jass' classification revisited.
BACKGROUND: In 1986, Jass and colleagues claimed to have improved on Dukes' classification of prognosis for carcinoma of the colon and rectum. To have clinical relevance, such results should be reproducible and confirmed by other institutions. STUDY DESIGN: Retrospective clinicopathologic study of 312 carcinomas of the colon and rectum to determine whether or not Jass' classification is superior to that of Dukes' as assessed by their relative reproducibility and prognostic significance. RESULTS: Dukes' classification had excellent intraobserver and interobserver reproducibility (kappa values of 0.86 and 0.93, respectively). In contrast, the reproducibility of variables assessed by Jass showed only slight to fair agreement (lymphocytic infiltration: intraobserver and interobserver kappa values of 0.08 and 0.05, respectively, growth pattern: intraobserver and interobserver kappa values of 0.37 and 0.41, respectively). Dukes' stage and patient age were the most important prognostic variables on multivariate regression analysis. Tumor differentiation, nuclear polarity, tubule configuration, and lymphocytic infiltration remained significantly related to survival in the presence of Dukes' stage and age. The model which best predicted prognosis was a combination of Dukes' stage, patient age and tumor differentiation. Further addition of the variables assessed by Jass to this model did not significantly improve the prediction of prognosis. CONCLUSIONS: Dukes' classification is of greater prognostic value and more reproducible than the components of Jass' classification. The continued use of Dukes' classification is, therefore, warranted for prognostic and therapeutic decisions in patients with carcinoma of the colon and rectum.
Colorectal carcinoma: importance of clinical and pathological factors in survival.
A series of clinicopathological variables was assessed on 312 patients undergoing surgical resection for primary colorectal cancer. Although the presence of venous invasion was related to mortality (P = 0.02), classifying invasion into involvement of thick-walled or thin-walled veins did not produce a variable of prognostic value. Intestinal obstruction (P = 0.04) and the macroscopic appearance of the tumour (P = 0.04) were related to mortality from colorectal cancer, but not from all causes of death. Duke's stage, increasing patient age and poorly differentiated tumours were the variables which were individually most significantly related to poor prognosis (P < 0.001 for each analysis). Cox's regression analysis identified these three variables as independent predictors of outcome in colorectal cancer. This study confirms that Duke's stage, patient age and tumour differentiation are still the most important clinicopathological variables in colorectal cancer.