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Biomedical subjects

B J Rowlands

Publications and source records attributed to B J Rowlands.

At least 37 records · Page 2Linked to original sources

Traumatic diaphragmatic rupture: associated injuries and outcome.

A retrospective case note analysis was performed on all patients treated for traumatic diaphragmatic rupture (TDR) at a major teaching hospital between January 1990 and August 1998. Patients were identified from the prospectively maintained UK Trauma and Research Network Database. Of the 480 cases of torso trauma admitted during the study period, 16 (3.3%) had TDR. Blunt trauma accounted for 13 (81%) of the injuries. A radiological pre-operative diagnosis was made in 10 (62.5%) patients. Seven of these were made on initial chest radiography, two on ultrasound scan and one on computed tomography. All patients underwent a midline laparotomy and TDR was subsequently diagnosed at operation in 6 patients. The left hemidiaphragm was ruptured in 14 (87.5%) patients and there was visceral herniation in 8 (50%). Twelve patients with blunt trauma had associated abdominal and extra-abdominal injuries, but only one of the three patients with penetrating trauma had other injuries. The median Injury Severity Score (range) was 21 (9-50). The median time (range) spent on the intensive care unit was 2 days (0-35 days). Pulmonary complications occurred in 7 (44%) patients. Two (12.5%) patients died from associated head injuries. TDR results from blunt and penetrating torso trauma, is uncommon, rarely occurs in isolation and is associated with a high morbidity and mortality. A high index of suspicion makes early diagnosis more likely as initial physical and radiological signs may be lacking.

Adolescent↗

Management of pancreatic pseudocysts.

BACKGROUND: This review analyses the outcome for patients with acute and chronic pancreatic pseudocysts managed in two major referral centres. PATIENTS AND METHODS: From 1987 to 1997, 33 patients were treated with either acute (n = 19) or chronic (n = 14) pseudocysts. Procedures performed included cystgastrostomy (64%), cystduodenostomy (6%), cystjejunostomy (3%), distal pancreatectomy with resection of pseudocyst (12%), laparotomy with external drainage (9%), endoscopic transpapillary stenting (3%) and endoscopic pancreatic duct sphincterotomy with percutaneous drainage of the pseudocyst (3%). RESULTS: All patients had resolution of their pseudocyst and no patient developed recurrence. There were no deaths in this series. There was a 9% incidence of major complications and a 21% incidence of minor complications. Outcome was excellent in 63% and good in 27% of patients. Two patients (6%) had persistent chronic pain and one patient (3%) had evidence of exocrine pancreatic insufficiency with malabsorption. CONCLUSIONS: Surgical internal drainage of pancreatic pseudocysts can be performed safely with low morbidity and mortality provided patients are carefully selected and their medical management is optimized. Although minimally invasive techniques now offer a variety of treatment options, open surgical drainage is still indicated for a significant number of cases.

Acute Disease↗

Influence of hospital and clinician workload on survival from colorectal cancer: cohort study.

OBJECTIVE: To determine whether clinician or hospital caseload affects mortality from colorectal cancer. DESIGN: Cohort study of cases ascertained between 1990 and 1994 by a region-wide colorectal cancer register. OUTCOME MEASURES: Mortality within a median follow up period of 54 months after diagnosis. RESULTS: Of the 3217 new patients registered over the period, 1512 (48%) died before 31 December 1996. Strong predictors of survival both in a logistic regression (fixed follow up) and in a Cox's proportional hazards model (variable follow up) were Duke's stage, the degree of tumour differentiation, whether the liver was deemed clear of cancer by the surgeon at operation, and the type of intervention (elective or emergency and curative or palliative intent). In a multilevel model, surgeon's caseload had no significant effect on mortality at 2 years. Hospital workload, however, had a significant impact on survival. The odds ratio for death within 2 years for cases managed in a hospital with a caseload of between 33 and 46 cases per year, 47 and 54 cases per year, and >/=55 cases per year (compared to one with </=23 cases per year) were respectively 1.48 (95% confidence interval 1.03 to 2.13), 1.52 (1.08 to 2.13), and 1.18 (0.83 to 1.68). CONCLUSIONS: There was no detectable caseload effect for surgeons managing colorectal cancer, but survival of patients treated in hospitals with caseloads above 33 cases per year was slightly worse than for those treated in hospitals with fewer caseloads. Imprecise measurement of clinician specific "events rates" and the lack of routinely collected case mix data present major challenges for clinical audit and governance in the years ahead.

Adult↗

The effects of l-arginine on crypt cell hyperproliferation in colorectal cancer.

BACKGROUND: Colonic crypt cell hyperproliferation characterizes malignant and premalignant conditions of the colon and may be modified by dietary manipulation. This study compared the effect of dietary arginine supplementation on colonic crypt cell proliferation during the initiation and promotion stages of colorectal carcinogenesis. MATERIALS AND METHODS: One hundred and twenty male Wistar rats were divided into 5 groups of 24 animals each. Groups D, DA, FA, and LA received subcutaneous injections of 1, 2-dimethylhydrazine for 20 weeks. Group D received no arginine supplement. l-arginine was given as a 1% solution instead of drinking water to Group DA for 22 weeks, to Group FA for the first 10 weeks, and to Group LA for the last 12 weeks. EDTA animals were given subcutaneous injections of EDTA for 20 weeks. Colonic crypt cell proliferation was assessed in 6 animals from each of the five groups and in 6 normal rats not given DMH or EDTA. RESULTS: The BrdUrd-labeling index and proliferative zone were significantly decreased in all arginine groups (DA, FA, LA). The greatest reduction was evident in Group FA in which tumor incidence and tumor size were also significantly lowered. CONCLUSIONS: When given during the initiation phase of carcinogenesis l-arginine significantly reduced colorectal tumor production and crypt cell hyperproliferation.

1,2-Dimethylhydrazine↗

Changes in weight, fluid balance and serum albumin in patients referred for nutritional support.

BACKGROUND AND AIMS: Starvation and injury impair the excretion of an excess sodium and water load, resulting in oedema and hypoalbuminaemia, which may have adverse effects on gastrointestinal physiology. We have retrospectively assessed clinical signs and fluid balance in 44 adult patients referred for nutritional support for >== 10 days. METHODS: Clinical evidence of oedema was noted. Oedematous patients were managed with a low sodium (0-50 mmol/day), low volume (2 l/day) feed. Some also received albumin and a diuretic. Body weight was recorded daily and serum albumin three times weekly. The lowest recorded weight during nutritional support and the weight at the time of discharge were correlated with serum albumin concentration. RESULTS: The 21 patients with oedema had acute surgical conditions and complications such as sepsis while the 23 non-oedematous patients had chronic conditions with gradual nutritional depletion. During nutritional support the mean (SEM) weight in kg of the oedematous patients fell from 79.3 (2.9) to 69.2 (3.2) (P>> 0.00001) and subsequently rose to 70.1 (3.2) (P= 0.005). Corresponding values for the non-oedematous patients were 61.4 (4.0), 60.2 (3.9) (P>> 0.05) and 61.2 (3.7) (P= 0.002) respectively. Weight reduction reflected negative salt and water balance and correlated with a rise in serum albumin (r = -0.61 for oedematous and r = -0.65 for non-oedematous patients) largely reflecting reversal of previous dilution. CONCLUSION: These findings have important implications for the salt and water content of perioperative fluid and nutritional prescriptions. They also emphasize the dilutional component of hypoalbuminaemia in these patients.

Albumins↗

Characterization of the Kupffer cell response to exogenous endotoxin in a rodent model of obstructive jaundice.

BACKGROUND: Sepsis and endotoxaemia occur frequently in biliary obstruction. Impaired Kupffer cell endocytosis is implicated in these events. Tumour necrosis factor and interleukin 6, secreted by Kupffer cells, are important mediators of sepsis. Kupffer cell clearance of endotoxin and secretion of cytokines in experimental obstructive jaundice were investigated. METHODS: Wistar rats were randomized to bile duct ligation, sham operation or control. Groups (n = 8) were studied 1 and 3 weeks after operation. Kupffer cell function was assessed using in situ hepatic perfusion. RESULTS: Clearance of endotoxin was significantly depressed 1 week (median (interquartile range) 20.3 (10.5-27.1) per cent) and 3 weeks (22.1 (20.2-23.2) per cent) after bile duct ligation compared with that in respective sham animals (35.5 (29.9-41.6) and 40.9 (37.7-47.0) per cent) and controls (39.5 (37.3-46.8) per cent). Secretion of tumour necrosis factor was significantly greater 1 week (1113.7 (706.5-1436. 8) pg/ml) and 3 weeks (1118.2 (775.7-1484.1) pg/ml) following bile duct ligation compared with that in respective sham animals (114.3 (0-178.5) and 107.6 (63.7-166.4) pg/ml) and controls (0 (0-20.7) pg/ml). Interleukin 6 was not secreted by sham or control animals but was present in the perfusate from jaundiced animals at 1 and 3 weeks (52.5 (9.9-89.5) and 66.2 (60.2-193.1) pg/ml). CONCLUSION: These data demonstrate simultaneous impairment of Kupffer cell clearance of endotoxin and increased secretion of proinflammatory cytokines in experimental obstructive jaundice. These diverse responses may contribute to the development of sepsis-related complications in biliary obstruction.

Animals↗

Periampullary diverticula and pancreaticobiliary disease.

BACKGROUND: Periampullary diverticula (PAD) are extraluminal outpouchings of the duodenum arising within a radius of 2-3 cm from the ampulla of Vater. They are frequently encountered in elderly patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) and contribute to failure of ERCP. This review details the relationship of PAD to pancreaticobiliary disease and the influence of PAD on the management of patients. METHODS: The United States National Library of Medicine Medline database was searched for articles on and related to PAD published in English within the past 15 years. Major earlier works were also reviewed. RESULTS: The prevalence of PAD increases with age and could be as high as 27 per cent. PAD are associated with an incompetent sphincter of Oddi and colonization of bile duct with beta-glucuronidase-producing organisms. PAD are implicated in the pathogenesis of pigment common bile duct stones, but there is no conclusive evidence to associate them with cholecystolithiasis or pancreatitis. PAD are a major cause of failure of ERCP, but success rates of more than 90 per cent have been achieved in specialist centres. CONCLUSION: With an ageing population, there will be an increase in elderly patients with PAD and symptomatic pancreaticobiliary disease. Continuing improvements in radiological and endoscopic techniques should enable this vulnerable group to be treated effectively and safely.

Age Factors↗

Kupffer cell blockade, tumour necrosis factor secretion and survival following endotoxin challenge in experimental biliary obstruction.

BACKGROUND: Gram-negative sepsis and its sequelae frequently complicate invasive procedures in patients with obstructive jaundice. In response to endotoxin, Kupffer cells secrete tumour necrosis factor (TNF), a pivotal early mediator of sepsis. An investigation was carried out into the specific role of Kupffer cell TNF secretion following endotoxin challenge in obstructive jaundice. METHODS: Survival following intraperitoneal administration of endotoxin (2.0, 0.02 and 0.0002 mg per 100 g) was determined in rats following bile duct ligation (BDL) or sham operation. Plasma TNF concentration was quantified following endotoxin administration (0.0002 mg per 100 g) at 1, 2 and 6 h. Subsequently, the effect of Kupffer cell blockade by gadolinium chloride on survival and plasma TNF concentration was assessed. RESULTS: Jaundiced animals showed a significantly increased mortality rate following intraperitoneal injection of endotoxin 2.0 mg per 100 g (BDL 100 per cent versus sham 0 per cent) and 0.02 mg per 100 g (BDL 70 per cent versus sham 0 per cent; P = 0. 002, Fisher's exact test). Median plasma TNF concentration was significantly greater in jaundiced animals 1 h after endotoxin administration (BDL 943 (interquartile range (i.q.r.) 211-3900) pg/ml versus sham 64 (i.q.r. 47-127) pg/ml; P = 0.002, Mann-Whitney U test). Kupffer cell blockade with gadolinium chloride increased the survival rate following endotoxin administration in BDL animals (BDL-GdCl3 100 per cent versus BDL-saline 40 per cent; P = 0.0003, Fisher's exact test) and decreased median plasma levels of TNF (BDL-GdCl3 88 (i.q.r. 0-1065) pg/ml versus BDL-saline 16 550 (1255-29 360) pg/ml; P = 0.002, Mann-Whitney U test). CONCLUSION: Kupffer cell blockade improved survival and suppressed systemic TNF activity after endotoxin challenge. In obstructive jaundice, hypersecretion of TNF by Kupffer cells may supplement systemic cytokine production and be responsible for significant complications.

Animals↗

Intramucosal acidosis and the inflammatory response in acute pancreatitis.

OBJECTIVE: The aim of this study was to assess the host response and diminished bowel perfusion during acute pancreatitis. METHODS: A total of 19 patients admitted with established diagnoses of acute pancreatitis on the basis of clinical findings, elevated serum amylase to more than four times the upper limit or by contrast radiology. Patients were stratified into mild and severe pancreatitis using the Atlanta criteria. Blood samples were obtained from in-dwelling lines or direct venipuncture within 12 h of admission and 24 hourly thereafter for measurements of plasma endotoxin, EndoCab immunoglobulin (Ig)G and IgM antibodies, tumor necrosis factor (TNF), p55 TNF receptor, and IL-6. A gastric tonometer was inserted in place of a nasogastric tube for intramucosal pH evaluation. RESULTS: Episodes of endotoxaemia were more common and endotoxin concentration significantly higher at presentation in the severe group compared to the mild group of patients. A greater consumption of IgM antibody was found in those with severe disease. The decrease in IgM antibody concentration was shown to be a specific host response, as a fall in concentration of antibodies to a neutral antigen, tetanus toxoid, was not observed. Significantly greater elevations were found in p55 TNF receptor and IL-6 concentrations in the severe group in comparison to those suffering mild pancreatitis. Significant correlations were found between gastric intramucosal pH and EndoCab IgM antibody, p55 TNF receptor, and IL-6. CONCLUSIONS: These results suggest that endotoxemia, an acute inflammatory response, and a reduction in bowel perfusion may occur in severe acute pancreatitis. The endotoxemia and inflammatory response may be due to the permeation of bacteria and their breakdown products across a disrupted bowel mucosal barrier.

Acute Disease↗

The gastrointestinal tract as a barrier in sepsis.

The gastrointestinal tract is an organ of digestion and absorption which is metabolically active and has specific nutrient requirements. In health, it has an additional function as a major barrier, protecting the body from harmful intraluminal pathogens and large antigenic molecules. In disease states, such as sepsis when the mucosal barrier is compromised, micro-organisms and their toxic products gain access to the portal and systemic circulations producing deleterious effects. Under these circumstances, systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndrome (MODS) develop leading to deterioration and death of the patient in the intensive care unit. Therapeutic strategies for such patients in the intensive care unit aim to support general immune function and maintain the structure and function of the gastrointestinal tract. For these therapies to be successful, the underlying septic or necrotic focus must be ablated using appropriate surgical or other invasive techniques.

Digestive System↗

Blunt abdominal injuries.

The management of blunt abdominal injury (BAI) has undergone quite significant changes over recent years. The emphasis is now on the recognition and limitation of the underlying metabolic insult associated with severe abdominal injury. The concepts of damage control and non-operative management while seeming diametrically opposed have both found favour in selected patient groups. The interventional radiologist has opened a new dimension in the control of inaccessible bleeding and is able to contribute to non-operative approaches. The complimentary use of the methods of investigation available for BAI will also improve the accuracy and specificity of diagnosis allowing more appropriate management. Embracing these new concepts of management by all institutions dealing with trauma victims will hopefully reduce the morbidity and mortality of BAI.

Abdominal Injuries↗

The use of tonometry to predict mortality in patients undergoing abdominal aortic aneurysm repair.

OBJECTIVE: To assess the reliability of intramucosal pH (pHi) of the sigmoid colon, IL-6 concentration and the APACHE II score in predicting outcome in patients undergoing elective abdominal aortic aneurysm repair. DESIGN: Prospective study. METHODS: In 42 patients, measurements were made of the sigmoid pHi with the silicone tonometer and plasma IL-6 by enzyme linked immuno-sorbent assay (ELISA). The daily postoperative APACHE II scores were also calculated. In 29 patients a preoperative left ventricular ejection fraction was determined by gated radionuclide angiography. RESULTS: Four out of 42 patients who were studied died. The lowest perioperative pHi, the peak postoperative IL-6 concentration and APACHE II scores were significantly different in the survivors in comparison to the non-survivors. In the non-survivors, the fall in pHi preceded the time of patient's demise by at least 4 days. Significant correlations were observed between changes in pHi, IL-6 and APACHE II. Using receiver operating characteristic curves, pHi was shown to be the most predictive of mortality compared to the other variables. The simplicity, speed and practicality of using the tonometer adds to its superiority over the latter measurements. No relationship was found between ventricular ejection fraction, pHi and outcome. CONCLUSION: Although the number of patients is small, these results support pHi as a valuable predictor of outcome and also suggest a role for the gut in initiating the IL-6 and physiological responses.

APACHE↗

Lower limb ischaemia-reperfusion injury causes endotoxaemia and endogenous antiendotoxin antibody consumption but not bacterial translocation.

BACKGROUND: It has been suggested that reperfusion of the acutely ischaemic lower limb alters gut permeability. The effect of lower limb ischaemia-reperfusion on systemic endotoxin and antiendotoxin antibody concentrations and the incidence of bacterial translocation was investigated. METHODS: Systemic endotoxin and antiendotoxin antibody concentrations were measured in five groups of male Wistar rats: control, after 3 h of bilateral hind limb ischaemia alone, and after 3 h of bilateral hind limb ischaemia followed by 1, 2 or 3 h of reperfusion. A second experiment examined translocation of indigenous bacteria following 2 h of reperfusion in a similar model. RESULTS: Ischaemia followed by reperfusion for 1, 2 or 3 h caused a significant increase in plasma endotoxin concentration to mean(s.e.m.) 10.0(3.0), 44.8(19.2) and 20.2(6.2) pg/ml compared with that in control animals (2.58(0.91) pg/ml) or animals in the ischaemia alone group (1.2(0.9) pg/ml) (P < 0.05). This was associated with a significant reduction in endogenous antiendotoxin antibody (immunoglobulin (Ig) G and IgM) concentration. No significant bacterial translocation was detected in any of the groups studied. CONCLUSION: These results demonstrate that a remote and isolated ischaemia-reperfusion injury to the lower limb, in the absence of infection or bacterial translocation, causes endotoxaemia. Further studies are needed to evaluate the role of endogenous antiendotoxin antibodies in this situation.

Animals↗

Diagnosis and treatment of sphincter of Oddi dysfunction.

UNLABELLED: BACKGROUND Sphincter of Oddi dysfunction is a challenge from both the diagnostic and therapeutic point of view. There is much ongoing debate about the accuracy and usefulness of various diagnostic tests, as there is about the effectiveness of proposed therapeutic alternatives. METHODS: A comprehensive review of the past 15 years' literature was undertaken, using the Medline database and cross-referencing of major articles on the subject. RESULTS AND CONCLUSION: Endoscopic and surgical treatments result in similar outcomes, with considerable failure rates. The latter reflect the difficulties in accurate diagnosis and a lack of sound objective criteria for selecting patients for intervention. In addition, in some patients sphincter of Oddi dysfunction may be only part of a generalized motility disorder of the gastrointestinal tract.

Cholangiopancreatography, Endoscopic Retrograde↗

Nutritional modulation of gut inflammation.

Nutritional therapy is an important component of the management of gastrointestinal inflammation, which disrupts the gut mucosal barrier leading to sepsis, SIRS and MODS. Future studies will be needed to define the role of specific nutrients in enhancing mucosal barrier function and supporting general immune function, and how this affects morbidity and mortality of critically-ill patients.

Animals↗

Conclusive evidence of endotoxaemia in biliary obstruction.

BACKGROUND: Endotoxaemia is implicated in the pathophysiology of obstructive jaundice. The EndoCab enzyme linked immunosorbent assay (ELISA) is a novel assay which measures endogenous antibody (IgG) to the inner core region of circulating endotoxins (ACGA). AIMS: To investigate the significance of endotoxaemia in biliary obstruction using the EndoCab assay and assess the specificity of the humoral response to endotoxin compared with an exogenous antigenic challenge (tetanus toxoid, TT). METHODS: Three groups of adult male Wistar rats were studied: no operation, sham operation, and bile duct ligation for 21 days (BDL). In the second study, rats rats received prior immunisation with TT. RESULTS: In the preliminary experiment, plasma ACGA was significantly increased in the BDL group (306.6 (18.3)% versus 119.9 (6.7)% and 105.2 (4.6)% in the sham and no operation groups, respectively; p < 0.001). Although the mean endotoxin concentration in the BDL group was greater than that in the control groups this was not significant. There was a strong positive correlation between ACGA and endotoxin concentrations (p = 0.0021). In the second study mean ACGA after 21 days of BDL was significantly elevated (267.1 (31.2)% versus 101.6 (21.2)% at baseline, p < 0.0001). ACGA was unaffected in the other two groups. TT antibody concentrations fell in all three groups; only in the BDL group was the fall significant (97.6 (5.3)% versus 78.8 (4.2)% at baseline, p < 0.05). CONCLUSIONS: The specific rise in ACGA supports the hypothesis that endotoxin has an integral role in the pathophysiology of obstructive jaundice. The production of anticore glycolipid antibodies specifically reflects systemic endotoxaemia in this model. The EndoCab assay provides a novel, sensitive, and specific method for endotoxin detection.

Animals↗