Failure of macrophage activation in experimental obstructive jaundice: association with bacterial translocation.
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Biomedical subjects
Publications and source records attributed to B J Rowlands.
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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.
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.
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The prognostic power of the extent of tumour invasion is indisputable; Dukes' classification has repeatedly been proven to be strongly correlated with patient survival. Modifications have led only to confusion, resulting in caution being required in the classification of patients with Dukes' A tumours. In the UK, the American tumour node metastasis and Australian clinicopathological systems are frequently considered too complex for routine clinical use. Meanwhile, Jass's classification may be complicated by observer variation between pathologists, and recent evidence suggests that it offers no advantage over that of Dukes. All the conventional staging systems also fail to take the skill of the surgeon into account when determining outcome. Attempts at quantifying tumour structure have not heralded the expected major advance. For instance, the expense and uncertain prognostic value of tumour DNA content assessed by flow cytometry are likely to restrict widespread use of this technique. It may soon be possible, however, to provide optimum treatment for patients based on individual tumour doubling times. Classification using knowledge of how a small number of cells in the tumour have the ability to invade locally, enter blood vessels and metastasize would also provide important prognostic information on which treatment could be based. Until then, the ease of use and high prognostic power of Dukes' classification ensure that, after 60 years, it is still the 'gold standard' against which all other prognostic classifications in colorectal cancer should be assessed.
A protocol was developed for the analysis of volatile short chain fatty acids in microsamples of feces, short chain fatty acid (SCFA) extraction was from fecal samples using ethanol incorporating n-hexanoic acid as an internal standard. The SCFAs were converted to pentafluorobenzyl esters with alpha-2,3,4,5,6-pentafluorotoluene and analyzed on a gas-liquid chromatograph equipped with an electron capture detector. One hundred milligrams of sample was routinely used but analysis could be carried out on 20 mg of sample.
Selective decontamination of the digestive tract (SDD) aims to reduce the rate of nosocomial infections in critical care patients. Pseudomonas spp. are common nosocomial pathogens and in this study isolates collected from patients and the environment during an SDD trial were examined. The study enrolled 161 SDD cases and 170 controls. Pseudomonads were isolated from 27% of SDD patients and 30% of controls. SDD partially suppressed colonization in the 'gastro-respiratory' mucosae but not in the rectum. A total of 108 isolates of pseudomonads were recovered from the environment. Resistance in rectal isolates was minimal but isolates from 'gastro-respiratory' sites showed increasing aminoglycoside resistance. Eighty-six per cent of aminoglycoside-resistant isolates from both patient groups and environment were pyocine type 1x. Episodes of infection were reduced in the SDD patients (6) compared with the controls (16), aminoglycoside-resistant strains being associated with zero episodes in SDD patients but with five in the control group.
Specific biochemical and physiological tests of liver function were used to assess 20 consecutive patients undergoing prolonged head and neck surgery with halothane or isoflurane anaesthesia. Hepatic function was assessed by measurement of serum concentrations of total bilirubin and albumin, and plasma activity of pseudocholinesterase, gamma-glutamyl transferase (GGT), aspartate transaminase (AST), alkaline phosphatase (ALP) and hepatic glutathione S-transferase. Plasma clearance of indocyanine green was used as an estimate of hepatic blood flow. No major differences were observed in serum concentrations of GGT, ALP, bilirubin, albumin or pseudocholinesterase. Serum AST activity in those patients receiving halothane was increased at 24 h and at 48 h compared with those who received isoflurane (not statistically significant). Glutathione S-transferase activity was increased significantly in the halothane group throughout the period of study, compared with those who received isoflurane. Similarly, there was a significant difference between the two groups as measured by plasma clearance of indocyanine green: in the halothane group there was a slower disappearance rate of the dye from plasma at specific times than in the patients who received isoflurane. Our data support the use of isoflurane rather than halothane for prolonged anaesthesia.
Following surgical stress the jejunum actively metabolizes endogenous glutamine, a non-essential amino acid, to produce alanine and ammonia, which augments substrate flow to the liver at a time when oral intake of nutrients is decreased. Oral glutamine supplementation theoretically may modify the response to injury. This study was designed to demonstrate the role of the jejunum in postinjury glutamine metabolism and to evaluate the influence of enteral glutamine supplements on nitrogen and ammonia metabolism after laparotomy and bowel resection in dogs. Oral glutamine in the presence of an intact small bowel significantly improved nitrogen balance (461 mg kg body-weight-1 day-1) compared with a control diet (-370 mg kg-1 day-1) (P less than 0.05, analysis of variance). Removal of the proximal small bowel prevented this beneficial effect of glutamine (-507 mg kg-1 day-1). Glutamine-supplemented and control diets were associated with similar portal ammonia concentrations throughout the study.
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In the development and management of a steroid-induced stupor, in a 17-year-old man, the dose and route of administration of steroid medication were felt to be important aetiological factors. A co-ordinated plan of management involving the physician, surgeon and psychiatrist is needed in such cases.
To evaluate the use of selective decontamination of the digestive tract (SDD) (polymyxin, amphotericin, tobramycin, and intravenous cefotaxime) in a mixed intensive care unit, we performed a stratified, randomized, prospective study. The 331 patients were recruited over an 18-month period, with 256 patients remaining more than 48 hours. Stratification by acute physiology and chronic health evaluation (APACHE II) preceded randomization to control (standard antibiotic therapy) or treatment (SDD) groups. Nosocomial infection was significantly reduced in the SDD group (16.7%; 21 of 126 patients) compared with the control group (30.8%; 40 of 130 patients; p = 0.008). No difference was found in overall mortality rate or length of stay between the two groups. Those patients with admission APACHE II scores 10 to 19 demonstrated the most significant reduction in nosocomial infection (23 of 70 control vs 13 of 76 SDD; p = 0.03) and mortality (15 of 70 control vs 8 of 76 SDD; p = 0.07). Emergence of multiresistant microorganisms was not a clinical problem, but a definite change occurred in the ecology of environmental and colonizing bacteria. With the exception of cefotaxime, a reduction was noted in systemic antibiotic usage in the SDD group. We conclude that SDD is useful in selected patients in a mixed intensive care unit.
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