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Biomedical subjects

Brian J Rowlands

Publications and source records attributed to Brian J Rowlands.

13 recordsLinked to original sources

Early postoperative jejunostomy feeding with an immune modulating diet in patients undergoing resectional surgery for upper gastrointestinal cancer: a prospective, randomized, controlled, double-blind study.

BACKGROUND: The provision of perioperative immune modulating enteral feeds after major surgery may result in reduced infective complications, but meta-analyses have not demonstrated a survival advantage. The aim of this study was to determine whether early postoperative immune modulating jejunostomy feeding results in reduced infective complications in patients undergoing resectional surgery for upper gastrointestinal cancer. METHODS: A total of 120 patients undergoing resection for cancers of the pancreas, oesophagus and stomach were randomized in a double-blind manner to receive jejunostomy feeding with an immune modulating diet (Stresson-Group A) or an isonitrogenous, isocaloric feed (1250 Calories and 75 g protein/l--Nutrison High Protein-Group B) for 10-15 days. Feeding was commenced 4h postoperatively and continued for 20 h/day. The target volume (ml/h) was 25 on day 0, 50 on day 1, and 75 thereafter. Outcome measures included complications, hospital stay and mortality. RESULTS: A total of 108 patients (54 in each group) were analysed. Feed delivery, although less than targeted, was similar in both groups. There were 6 (11%) deaths in each group. Median (IQR) postoperative hospital stay was 14.5 (12-23) days in Group A and 17.5 (13-23) days in Group B (P=0.48). A total of 24 (44%) patients in each group had infective complications (P=1.0). A total of 21 (39%) patients in Group A and 28 (52%) in Group B had non-infective complications (P=0.18). Jejunostomy-related complications occurred in 26 (48%) patients in Group A and 30 (56%) in Group B (P=0.3). CONCLUSION: Early postoperative feeding with an immune modulating diet conferred no outcome advantage when compared with a standard feed.

Adjuvants, Immunologic↗

Squamous cell carcinoma of the pancreas: report of a case and review of the literature.

CONTEXT: Although, squamous metaplasia of the ductal columnar cells can be observed during periods of inflammation, squamous cell pancreatic carcinoma is an extremely rare tumour. CASE REPORT: We present the case of a 72-year-old man who presented to our hospital with painless obstructive jaundice. After careful and adequate staging investigations that revealed a malignant mass in the head of pancreas he underwent a laparotomy which revealed an inoperable pancreatic cancer. Palliative bypass procedure was done. The biopsy specimens revealed a squamous cell cancer. CONCLUSION: Pure squamous cell carcinoma of the pancreas is a very rare malignancy. In most cases it is not possible to make a pre-operative histological diagnosis and curative resection is unlikely because of dissemination at the time of initial diagnosis or laparotomy.

Aged↗

Combined antioxidant therapy reduces pain and improves quality of life in chronic pancreatitis.

Patients with chronic pancreatitis (CP) typically suffer intractable abdominal pain that is resistant to most analgesic strategies. Recent research indicates that the pain of CP may be in part due to oxygen free radical induced pancreatic damage. Using a randomized, double-blind, placebo-controlled crossover trial, we evaluated the efficacy of a combined antioxidant preparation in the management of CP. Patients with confirmed chronic pancreatitis (N = 36) were randomized to receive treatment with either Antox, which contains the antioxidants selenium, betacarotene, L-methionine, and vitamins C and E, or placebo for 10 weeks. Each group of patients then switched to receive the alternative treatment for a further 10 weeks. Markers of antioxidant status were measured by blood sampling, whereas quality of life and pain were assessed using the SF-36 questionnaire. Nineteen patients completed the full 20 weeks of treatment. Treatment with Antox was associated with significant improvements in quality of life in terms of pain (+17 antioxidant vs. -7 placebo), physical (+9 vs. -3) and social functioning (+8 vs. -7), and general health perception (+10 vs. -3). We conclude that treatment with antioxidants may improve quality of life and reduce pain in patients suffering from chronic pancreatitis.

Abdominal Pain↗

Ethylene diamine tetraacetic acid-induced colonic crypt cell proliferation in rats.

AIM: To investigate the effect of ethylene diamine tetraacetic acid (EDTA) on proliferation of rat colonic cells. METHODS: EDTA was administered into Wistar rats, carcinogenesis induced by 1,2-dimethylhydrazine (DMH) in rats was studied with immunohistochemistry. RESULTS: Marked regional differences in cell proliferation were found in all groups. In EDTA-treated animals, total labelling indexes in both proximal (10.00 +/- 0.44 vs 7.20 +/- 0.45) and distal (11.05 +/- 0.45 vs 8.65 +/- 0.34) colon and proliferative zone size (21.67 +/- 1.13 vs 16.75 +/- 1.45, 27.73 +/- 1.46 vs 21.74 +/- 1.07) were significantly higher than that in normal controls (P<0.05) and lower than that in DMH group (10.00 +/- 0.44 vs 11.54 +/- 0.45, 11.05 +/- 0.45 vs 13.13 +/- 0.46, 21.67 +/- 1.13 vs 35.52 +/- 1.58, 27.73 +/- 1.46 vs 39.61 +/- 1.32, P<0.05). Cumulative frequency distributions showed a shift of the EDTA distal curve to the right (P<0.05) while the EDTA proximal curve did not change compared to normal controls. Despite the changes of proliferative parameters, tumours did not develop in EDTA treated animals. CONCLUSION: Hyperproliferation appears to be more easily induced by EDTA in distal colon than in proximal colon. Hyperproliferation may need to exceed a threshold to develop colonic tumours. EDTA may work as a co-factor in colonic tumorigenesis.

Adenocarcinoma↗

Early and long-term results of surgery for severe necrotising pancreatitis.

BACKGROUND: Necrotising pancreatitis is a challenging problem for the surgeon, as it is associated with considerable morbidity and mortality. The indications, timing of surgical intervention and type of procedure continue to be debated in an effort to improve the outcome of this devastating disease process. METHODS: A retrospective analysis of early and long-term results in a series of 44 consecutive patients (34 men, 10 women, median age 46.5, range 13-74 years) who underwent necrosectomy for severe necrotising pancreatitis. In 16 patients necrosectomy and primary abdominal closure with drains was performed, 14 patients had planned staged necrosectomy and delayed abdominal closure with drains, and in 14 patients necrosectomy with open laparostomy was undertaken. RESULTS: There were 8 deaths (18%) and 14 cases (32%) of significant hospital morbidity (fistula 10, pseudocyst 2, renal failure 2). Variables which correlated with mortality were: high APACHE II score, acute renal failure requiring dialysis, and requirement for surgical intervention at an early stage (within the first two weeks). A total of 28 late complications occurred in 21 of the surviving patients (endocrine pancreatic insufficiency 10, exocrine pancreatic insufficiency 2, pseudocyst 2, chronic renal failure 2, incisional hernia 10, recurrent pancreatitis 1, and chronic pain 1). CONCLUSIONS: Low mortality can be achieved in patients with severe necrotizing pancreatitis with aggressive surgical intervention and careful perioperative management. Long-term morbidity remains high, and emphasises the need for prolonged follow-up.

APACHE↗

Percutaneous biliary metal wall stenting in malignant obstructive jaundice.

BACKGROUND: Most patients with advanced stage malignant obstructive jaundice will be suitable for palliation only. Metallic stents are safe, effective and minimally invasive. DESIGN: A review of case notes of patients who had Wallstents inserted percutaneously from January 1996 to December 2000. RESULTS: Eighty-nine patients with a median age of 72 years underwent percutaneous insertion of biliary metal stents. The diagnoses were cholangiocarcinoma (41.5%), pancreatic carcinoma (40.5%), nodal metastases at the porta hepatis (14.6%) and gall bladder cancer (3.4%). Ninety-six per cent of patients improved their hyperbilirubinaemia to normal levels by 1 month. The median post-procedure hospital stay was 16 days. Early overall complications (within 30 days of stenting) occurred in 30% of patients (70% of these were disease related). The 30 day mortality rate was 20% (n = 18). Fifty (70%) patients were readmitted to hospital, most commonly because of carcinomatosis (16) or stent obstruction (12). The symptom-free period ranged from 2 weeks to 13 months. Median survival for all patients was 3.5 months. Survival correlated inversely with serum bilirubin at presentation (r = -0.34, P = 0.001), but not with other liver function tests. DISCUSSION: Metal wall stenting for malignant obstructive jaundice provides good palliation with low, procedure-related morbidity and mortality, but poor overall survival from disease-related morbidity. Survival significantly correlates with pre-stenting serum bilirubin levels. There is a need to identify the subgroup of patients in whom stenting has no beneficial effect.

Aged↗

Effect of salt and water balance on recovery of gastrointestinal function after elective colonic resection: a randomised controlled trial.

BACKGROUND: Low concentrations of albumin in serum and long gastric emptying times have been returned to normal in dogs by salt and water restriction, or a high protein intake. We aimed to determine the effect of salt and water balance on recovery of gastrointestinal function after elective colonic resection in human beings. METHODS: We randomly allocated ten patients to receive postoperative intravenous fluids in accordance present hospital practice (> or = 3 L water and 154 mmol sodium per day) and ten to receive a restricted intake (< or = 2 L water and 77 mmol sodium per day). All patients had no disease other than colonic cancer. The primary endpoint was solid and liquid-phase gastric emptying time, measured by dual isotope radionuclide scintigraphy on the fourth postoperative day. Secondary endpoints included time to first bowel movement and length of postoperative hospital stay. Analysis was by intention to treat. FINDINGS: Median solid and liquid phase gastric emptying times (T(50)) on the fourth postoperative day were significantly longer in the standard group than in the restricted group (175 vs 72.5 min, difference 56 [95% CI 12-132], p=0.028; and 110 vs 73.5 min, 52 [9-95], p=0.017, respectively). Median passage of flatus was 1 day later (4 vs 3 days, 2 [1-2], p=0.001); median passage of stool 2.5 days later (6.5 vs 4 days, 3 [2-4], p=0.001); and median postoperative hospital stay 3 days longer (9 vs 6 days, 3 [1-8], p=0.001) in the standard group than in the restricted group. One patient in the restricted group developed hypokalaemia, whereas seven patients in the standard group had side-effects or complications (p=0.01). INTERPRETATION: Positive salt and water balance sufficient to cause a 3 kg weight gain after surgery delays return of gastrointestinal function and prolongs hospital stay in patients undergoing elective colonic resection.

Aged↗

Complexities in ETS-domain transcription factor function and regulation: lessons from the TCF (ternary complex factor) subfamily. The Colworth Medal Lecture.

The ETS-domain transcription factor family can be divided into a series of subfamilies. Elk-1 represents the founding member of the ternary complex factor (TCF) subfamily. By focusing on the TCF subfamily, we can demonstrate the complexities that exist in the function and regulation of ETS-domain transcription factors. This article focuses on Elk-1 in detail and summarizes the functions of other TCFs. The key themes covered include the domain structure of the TCFs, the mechanisms of complex formation with serum response factor, regulation of TCFs by mitogen-activated protein kinase cascades, and transcriptional regulatory properties of the TCFs. Finally, the emerging role of the TCFs in vivo is discussed. A picture is developing indicating that, while these proteins exhibit significant sequence and functional conservation, key differences in their structure and regulation are being identified which may relate to unique functions of these proteins in vivo.

Amino Acid Sequence↗

Heterotopic pancreas in the spleen: malignant degeneration to mucinous cystadenocarcinoma.

We report the clinicopathological findings of a patient who presented with a primary splenic cystic tumour arising from heterotopic pancreatic tissue. The pancreas was normal on radiological and intraoperative examination. Histological analysis of the specimen demonstrated a mucinous cystadenocarcinoma with remnants of normal pancreatic tissue within the substance of the spleen. Immunohistochemistry characterized the tumour as being pancreatic in origin with overexpression of p53 protein. Five cases of primary mucinous cystadenocarcinoma of the spleen originating from heterotopic pancreatic tissue have been described; to our knowledge, this is the first case to provide conclusive immunohistochemical evidence to support this proposition.

Aged↗

Variability of cell proliferation in the proximal and distal colon of normal rats and rats with dimethylhydrazine induced carcinogenesis.

AIM: To investigate the patterns of cell proliferation in proximal and distal colons in normal rats and rats with 1,2-dimethylhydrazine (DMH) induced carcinogenesis using the thymidine analogue bromodeoxyuridine. METHODS: Colonic crypt cell proliferation was immunohistochemically detected using the anti-bromodeoxyuridine Bu20a monoclonal antibody. RESULTS: Marked regional differences were found in both groups. Total labelling index (LI) and proliferative zone size in both normal (8.65+/-0.34 vs 7.2+/-0.45, 27.74+/-1.07 vs 16.75+/-1.45) and DMH groups (13.13+/-0.46 vs 11.55+/-0.45, 39.60+/-1.32 vs 35.52+/-1.58) were significantly higher in distal than in proximal colon (P<0.05), although the number of cells per proximal crypt was greater (31.45+/-0.20 vs 34.45 +/-0.39, 42.68+/-0.53 vs 49.09+/-0.65, P<0.0001). Crypt length, total LI and proliferative zone size all increased in both proximal and distal regions of DMH rats compared to normal controls (P<0.0001). In DMH-treated rat colon a shift of labelled cells to higher crypt cell positions was demonstrated distally whilst a bi-directional shift was evident proximally (P<0.05). CONCLUSION: Our results show that changes in cell proliferation patterns, as assessed by bromodeoxyuridine uptake, can act as a reliable intermediate marker of colonic cancer formation. Observed differences between proliferation patterns in distal and proximal colon may be associated with the higher incidence of tumors in the distal colon.

Animals↗

Transduodenal sphincteroplasty and transampullary septectomy for sphincter of Oddi dysfunction.

BACKGROUND: The diagnosis and management of sphincter of Oddi dysfunction are controversial issues. Both surgical and endoscopic series report modest success in the treatment of this condition. There is evidence from endoscopic series that the Milwaukee classification could predict the clinical outcome after sphincterotomy. We reviewed our long-term results of surgical sphincter ablation for sphincter of Oddi dysfunction, in order to correlate outcome with underlining pathology (biliary versus pancreatic) and Milwaukee biliary group classification. PATIENTS AND METHODS: During a 10 year period (1987-1996), 36 patients with either biliary (n = 26) or pancreatic (n = 10) presentation of suspected sphincter of Oddi dysfunction were selected for surgery according to a standard protocol of investigation and management. All patients were classified according to the Milwaukee classification for the biliary group or its version for the pancreatic group and had transduodenal sphincteroplasty and transampullary septectomy. RESULTS: Despite a trend towards a better outcome in the biliary group (good result 62%, moderate 23%, poor 15%) compared to the pancreatic (good result 40%, moderate 40%, poor 20%) the difference was not statistically significant (P = 0.48). Milwaukee classification for the biliary group correlated well with a favourable outcome (P < 0.05). CONCLUSIONS: The modest outcome despite careful patient selection for surgery emphasises the need for more objective diagnostic tools. Milwaukee classification appears to be of good predictive value, and a good result can be anticipated in type I or even type II patients. The trend towards a better outcome in the biliary group may reflect the weakness of a drainage procedure to treat patients with parenchymal pancreatic disease.

Adolescent↗

Lower limb ischemia-reperfusion injury triggers a systemic inflammatory response and multiple organ dysfunction.

Restoration of blood flow to an acutely ischemic lower limb may, paradoxically, result in systemic complications and unexpected mortality. We investigated the effect of acute ischemia-perfusion of the lower limb on cytokine production and end organ function. Plasma concentrations of tumor necrosis factor-alpha (TNF-a) and interleukin-6 (IL-6) were determined in five groups of male Wistar rats: control, 3 hours of bilateral hind limb ischemia alone, and 3 hours of bilateral hind limb ischemia followed by 1 hour, 2 hours, or 3 hours of reperfusion, respectively. In a second experiment, the effect of lower limb ischemia-reperfusion on remote organs (lung, liver, and kidney) was assessed biochemically and histologically. There was a significant increase in plasma concentrations of TNF-a in plasma of animals subjected to 3 hours of bilateral hind limb ischemia followed by 1 hour of reperfusion, 40.1 +/- 4.4 pg/ml, when compared with controls, 22.6 +/- 4.4 pg/ml, or animals in the ischemia-alone group, 16.3 +/- 5.2 (p <0.05). Plasma concentration of IL-6 increased progressively and significantly in animals subjected to bilateral hind limb ischemia followed by 1 hour of reperfusion, 720 +/- 107 pg/ml; 2 hours of reperfusion, 1987 +/- 489 pg/ml; or 3 hours of reperfusion, 6284 +/- 1244 (p <0.0001), compared with controls, 104 +/- 43 pg/ml; or animals in the ischemia-alone group, 140 +/- 55 pg/ml. In the study comparing portal and systemic concentrations of IL-6, systemic concentrations of IL-6, 967 +/- 184 pg/ml were significantly higher than those in the portal circulation 577 +/- 127 pg/ml (p <0.05). There was a significant increase in plasma concentrations of urea, creatinine, aspartate transaminase, alanine transaminase, and lactic dehydrogenase in reperfused animals compared with controls (p <0.001). Morbidity and mortality following reperfusion of the acutely ischemic limb may be a manifestation of multiple organ dysfunction caused by a systemic inflammatory response triggered by reperfusion of the ischemic extremities.

Animals↗