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R F McMahon

Publications and source records attributed to R F McMahon.

At least 19 recordsLinked to original sources
PubMed2001

A randomized study to evaluate the effect of a perioperative infusion of dopexamine on colonic mucosal ischemia after aortic surgery.

PURPOSE: Colonic ischemia after aortic surgery is associated with increased mortality and morbidity rates. This study was conducted as a single-center side arm to a multicenter, randomized, placebo-controlled study to evaluate the effect of dopexamine hydrochloride on its incidence. METHODS: Thirty patients, mean age 65.1 years (range, 46-84), undergoing elective infrarenal aortic surgery were entered. Preoperative hemodynamic and respiratory parameters were optimized. Patients were then randomly assigned to receive a perioperative infusion of dopexamine at 2 microg/kg per minute (n = 12) or 0.9% saline placebo (n = 18). All patients underwent colonoscopy and biopsy preoperatively and 1 week postoperatively. Specimens were assessed for evidence of mucosal ischemia, presence of mast cell tryptase, myeloperoxidase activity, and both the inducible and endothelial isoforms of nitric oxide synthase. RESULTS: There was no significant difference in perioperative fluid and blood requirements or hemodynamic and respiratory parameters between the two groups. However, there was significantly less evidence of mucosal ischemic changes in dopexamine-treated patients (n = 1) compared with placebo (n = 8) (P =.049). Furthermore, when preoperative biopsies were compared with those performed 1 week postoperatively, nine (50%) patients in the placebo group and two (16.7%) in the dopexamine group scored worse. Although there was no significant difference in inflammatory markers between the two groups, both mast cell tryptase and myeloperoxidase expression were increased in patients with histologic evidence of ischemia (P <.05). Furthermore, inducible nitric oxide synthase staining within the vascular (P =.001) and lamina propria (P <.05) components of the mucosa was also significantly greater. CONCLUSION: A perioperative dopexamine infusion affords significant histologic protection to colonic mucosa after aortic surgery.

Adult↗
PubMed2000

Antioxidant properties of colchicine in acute carbon tetrachloride induced rat liver injury and its role in the resolution of established cirrhosis.

Antioxidant and antifibrotic properties of colchicine were investigated in the carbon tetrachloride (CCl(4)) rat model. (1) The protective effect of colchicine pretreatment on CCl(4) induced oxidant stress was examined in rats subsequently receiving a single lethal dose of CCl(4). Urinary 8-isoprostane, kidney and liver malondialdehyde and kidney glutathione levels increased following CCl(4) treatment, but only the rise in kidney malondialdehyde was significantly inhibited by colchicine pretreatment. Serum total antioxidant levels were significantly higher in the colchicine pretreatment group. (2) The long term effects of colchicine treatment on CCl(4) induced liver damage were investigated using liver histology and biochemical markers (hydroxyproline and type III procollagen peptide). Co-administration of colchicine with sub-lethal doses of CCl(4) over 10 weeks did not prevent progression to cirrhosis. However, rats made cirrhotic with repeated CCl(4) challenge and subsequently treated with colchicine for 12 months, all showed histological regression of cirrhosis. (3) The antioxidant effect of colchicine in vitro was evident only at very high concentrations compared to other plasma antioxidants. In summary, colchicine has only weak antioxidant properties, but does afford some protection against oxidative stress; more importantly, long term treatment with this drug may be of value in producing regression of established cirrhosis.

Animals↗
PubMed1999

Dopexamine reduces the incidence of acute inflammation in the gut mucosa after abdominal surgery in high-risk patients.

OBJECTIVE: To evaluate the effect of dopexamine on the incidence of acute inflammation in the stomach/duodenum in patients undergoing abdominal surgery > or =1.5 hrs with a minimum of one high-risk criterion. DESIGN: Prospective, randomized, double-blind, placebo-controlled study. This study was conducted as a side arm to a multicenter, multinational study. SETTING: University hospital in an adult intensive care unit. PATIENTS: Thirty-eight patients. INTERVENTIONS: Patients were stabilized with fluid, blood products, and supplementary oxygen to achieve predetermined goals: cardiac index > 2.5 L/min/m2, mean arterial blood pressure of 70 mm Hg, pulmonary arterial occlusion pressure of 10 mm Hg, hemoglobin of 100 g/L, and arterial saturation of 94%. After stabilization, the study drug (either placebo [group A], dopexamine 0.5 microg/kg/min [group B], or dopexamine 2.0 microg/kg/min [group C]) was commenced. The study drug infusion was started 2 to 12 hrs before surgery and infused for 24 hrs after surgery. Estimation of upper gut blood flow was assessed using a gastric tonometer, and gastroscopy with biopsy was performed before surgery (after induction of anesthesia) and 72 hrs after surgery. Comparisons were made between endoscopic findings and histologic proof of acute inflammatory changes. In addition, biopsies were assessed for the presence in the mucosa of mast cells, myeloperoxidase activity, and inducible nitric oxide synthase. MEASUREMENTS AND MAIN RESULTS: Intramucosal pH decreased significantly with time in all three groups (p < .001), reaching the lowest point at the end of surgery. There was no difference among the groups. Endoscopy visualized acute inflammatory changes in 58.3% of group A patients, 46.2% of group B patients, and 53.90% of group C patients after hemodynamic optimization. At 72 hrs, dopexamine-treated patients compared with placebo-treated patients had a significantly lower incidence of gastric and duodenal acute inflammatory changes, as defined by myeloperoxidase activity (37.5% in groups B and C vs. 86% in group A; p < .05). CONCLUSION: Dopexamine in doses of 0.5 and 2.0 microg/kg/min affords significant histologic protection to the upper gastrointestinal tract mucosa 72 hrs after operation in high-risk surgical patients undergoing abdominal surgery.

Abdomen↗
PubMed1998

Histological study of colonic ischaemia after aortic surgery.

BACKGROUND: Colonic ischaemia is a well documented complication of abdominal aortic reconstruction. In this prospective study patients had routine preoperative and postoperative colonoscopy and biopsy, in order to determine the true incidence and implications. METHODS: Fifty-six patients undergoing elective infrarenal aortic surgery, 28 for aneurysm and 28 for occlusive disease, had colonoscopy and biopsy before and 1 week after operation. RESULTS: Colonic ischaemia was identified histologically in biopsies from 16 (30 per cent) of 53 patients. Almost half the patients had normal macroscopic appearances. Two factors exhibited a statistically significant association with the development of ischaemia: prolonged cross-clamp time (P < 0.05) and postoperative diarrhoea (P< 0.001). Co-morbidity was much higher in patients with colonic ischaemia (P< 0.005). Overall morbidity was significantly greater in the aneurysm group (P < 0.05). CONCLUSION: Colonic ischaemia is common after aortic reconstruction. When suspected, colonoscopy with biopsy is diagnostic.

Aged↗
PubMed1998

Localisation and semiquantitative assessment of hepatic procollagen mRNA in primary biliary cirrhosis.

BACKGROUND: Chronic liver disease is characterised by excessive deposition of collagen and other extracellular matrix proteins, produced mainly, but not exclusively, by activated hepatic stellate cells in the perisinusoidal space. In primary biliary cirrhosis (PBC) fibrosis is concentrated mainly around the portal tracts. AIMS: To examine the hypothesis that, in addition to hepatic stellate cells, portal tract fibroblasts might play a significant role in the deposition of collagen in PBC. METHODS: Fifty liver biopsy specimens from patients with PBC were studied. An in situ hybridisation technique was adapted to localise and measure semiquantitatively type I procollagen mRNA in formalin fixed, paraffin wax embedded sections, using an 35S labelled cRNA probe specific for the alpha 1 chain of rat type I procollagen. Hepatic fibrogenic activity was also assessed using serum type III procollagen peptide (PIIINP). RESULTS: In PBC, type I procollagen gene expression was significantly increased. Signal was localised mainly in and around inflamed portal tracts, to cells which had the appearances of portal fibroblasts. Signal activity in these cells correlated with the degree of portal fibrosis and inflammation and also with serum PIIINP concentrations. CONCLUSIONS: Results are consistent with the hypothesis that the excessive extracellular matrix, deposited within the liver in PBC, is synthesised not only by hepatic stellate cells but also by portal tract fibroblasts. The semiquantitative assessment of procollagen mRNA in liver biopsy specimens may provide a useful method of evaluating the rate of synthesis of collagen and therefore disease activity in patients with PBC.

Biomarkers↗
PubMed1998

Stage 0 mucinous adenocarcinoma in situ of the urachus.

Adenocarcinomas of the urinary bladder are rare (1-5% of bladder tumours) and of notoriously poor prognosis. About one third of such tumours arise in urachal remnants related to the bladder. This is believed to be the first report of in situ change in the urachal remnant. The patient presented with mucusuria and computed tomography showed a typical urachal cyst. After excision the cyst was found to contain mucinous adenomatous epithelium but without invasion of the basal lamina. Pathological stage is the best prognostic indicator in urachal tumours. Prompt investigation and management of mucusuria may allow the diagnosis of urachal tumours in this preinvasive stage.

Adenocarcinoma, Mucinous↗
PubMed1997

South Asians with ulcerative colitis exhibit altered lectin binding compared with matched European cases.

Ulcerative colitis is associated with abnormalities of mucin synthesis and secretion, features that may also be associated with malignant change. It has been shown that South Asians in Britain have a high incidence of ulcerative colitis but a low incidence of colorectal carcinoma compared with their European counterparts. Previous studies have demonstrated changes in colonic mucin sialylation and sulphation in both South Asian and European cases with ulcerative colitis. This was related to disease severity, but changes were also found in quiescent disease. The aim of the present study was to determine glycoconjugate expression in the colon from South Asian cases and to compare results with those from a group of affected Europeans. Glycans were identified in formalin-fixed, paraffin-embedded tissue from 17 South Asian patients with ulcerative colitis and from 11 European patients with a similar degree of colitis, by the application of 10 biotinylated lectins. These were directed against a range of sialyl, fucosyl and 2-deoxy, 2-acetamido-galactosyl sequences, using an avidin-peroxidase revealing system and semiquantitative assessment. The South Asian group showed a reduction in the binding of agglutinins from Sambucus nigra in the apical-membranous region of enterocytes, and a decrease in apical Maackia amurensis agglutinin binding. These results suggest that South Asians with ulcerative colitis show a different distribution of terminal N-acetyl neuraminyl residues, either in their alpha-2,6 or alpha-2,3 linkage, compared with their European counterparts. The changes in sialylation observed in European cases compared with normal disease-free control subjects were present in quiescent disease, but were also related to disease activity. Their absence in Asians with ulcerative colitis may imply an inherent, genetically determined variation in this group, which may also play a part in their reduced risk of subsequent malignancy.

Asia, Southeastern↗
PubMed1996

Giant cell hepatitis associated with systemic lupus erythematosus.

Giant hepatocytes are commonly found in several neonatal and infantile liver diseases, but are rarely found in adult liver disease. A 42 year old white woman presented with a five month history of paraesthesia and numbness of both the upper and lower limbs and with vague abdominal pain. Abnormal liver function was noted on routine screening. Ultrasound scan of the abdomen showed gallstones; barium enema, ERCP and computed tomography scan were all normal. IgG antibodies to double stranded DNA were present at a titre of 40 units. Anti-cardiolipin antibodies, anti-mitochondrial antibodies and rheumatoid factor were not detected. Serology for hepatitis A, B, C, and paramyxoviruses was negative, as was the Paul Bunnell test. A clinical diagnosis of systemic lupus erythematosus (SLE) with an axonal sensory polyneuropathy was made, the latter confirmed on biopsy of the sural nerve. Giant cells were noted on liver biopsy. The patient was treated with corticosteroids; liver function had improved after two years of follow up. When extensive giant cell transformation is noted on liver biopsy, particularly when neuropathy is also a feature, the possibility of an association with SLE should be considered.

Adult↗
PubMed1995

Hepatitis C-related chronic liver disease among asymptomatic blood donors in the north west of England.

In the first 19 months of screening, the North Western Regional Transfusion Centre (RTC) tested 224,000 consecutive blood donors for antibody to hepatitis C virus (anti-HCV) by second generation enzyme immunoassay (EIA). Of these, 366 repeatedly reactive samples were referred for confirmatory testing at Manchester Public Health Laboratory (PHL). There, the initial EIA was repeated, together with two further EIAs. All the referred samples were subjected to a confirmatory line immunoblot (RIBA-II). Reverse transcription followed by the polymerase chain reaction (RT-PCR), in order to detect viral RNA, was performed on selected samples. Among the donors, 61 accepted offers for medical review and were assessed for risk factors, clinical findings and results of standard liver function tests. Of these donors, 53 proceeded to liver biopsy. The overall prevalence of confirmed positive donors was 0.04%. Main risk factors identified included intravenous drug abuse in 31 (51%) donors and prior blood transfusion in 12 (20%) but a risk factor was not apparent in 11 (18%). Viraemia, detected by RT-PCR, could be predicted with a high degree of accuracy by means of the readily available and simpler screening and confirmatory tests (EIA and RIBA-II). Established chronic hepatitis was demonstrated in 90% of the liver biopsies. A trend towards worsening histological findings accompanied increasing concentrations of serum transaminase. Even so, many donors with normal transaminase values had abnormal biopsies including those showing chronic active hepatitis (CAH). These findings indicate that a substantial proportion of previously unrecognised asymptomatic persons with established chronic liver disease exists among North Western blood donors.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Can histopathologists diagnose bronchopneumonia?

OBJECTIVES: To assess histopathologists' ability to accurately diagnose bronchopneumonia, both on naked eye and microscopic examination; to extrapolate from the error rate to determine whether the role of the necropsy in monitoring the epidemiology of clinical error might be compromised. METHODS: Review of archival histological sections and necropsy reports from two teaching hospitals in Manchester. The main outcome measures identified were the proportions of macroscopic diagnoses of bronchopneumonia which were confirmed by the original pathologist on histological examination, and which could be confirmed on histological review by independent pathologists, together with the proportion of discrepant diagnoses remedied in the final report by the original pathologist. RESULTS: Of 279 cases where a macroscopic diagnosis of bronchopneumonia had been noted in the original provisional necropsy report, the original histopathologist described bronchopneumonia in only 206 (73.8%) in the subsequent final report, which took histology into account. Bronchopneumonia could be confirmed on independent histological review in only 193 (69.2%) of these cases. The original histopathologist diagnosed 74 cases of bronchopneumonia on histological grounds only, of which only 57 (77.0%) could be confirmed on review. Of a total of 160 discrepancies between the original naked eye diagnoses and the final reviewed diagnoses, only 130 (81.3%) had been remedied by the original pathologist. CONCLUSIONS: There is a considerable discrepancy rate between naked eye diagnoses of bronchopneumonia at necropsy and diagnoses confirmed on microscopy. If this discrepancy rate is extrapolated to other common lesions, then the role of the necropsy in clinical audit may be compromised. Pathologists need to take steps to monitor and improve their own diagnostic standards.

Autopsy↗
PubMed1995

Amyloid tumour of the colon.

A case of amyloid tumour of the colon and the first in association with a carcinoma is reported. A previously healthy 65 year old man presented with non-specific symptoms of lower abdominal pain and flatulence without rectal bleeding. A clinical diagnosis of diverticular disease was made and colonoscopy performed. Two lesions (one at 15 cm and the other at 30 cm from the anal margin) were found on endoscopy and removed. On histology, the lesion at 15 cm was a moderately differentiated adenocarcinoma and that at 30 cm contained amyloid. Further tests (standard tinctorial methods and immunohistochemistry) revealed the 30 cm lesion to be an amyloid tumour of the colon of AL (lambda) type. When biopsy of an atypical, large, solitary colorectal lesion reveals amyloid deposition, the possibility of an amyloid tumour should be considered and the lesion resected.

Adenoma, Villous↗
PubMed1994

Glycoconjugates of the normal human colorectum: a lectin histochemical study.

Previous studies of the normal human colorectum by lectin histochemistry have used a mixture of tissues, including those derived from colons harbouring neoplasia and inflammatory bowel diseases. In the current investigation, tissues from patients without either of these conditions have been examined with a wide panel of lectins, encompassing specificities directed against both N- and O-linked sequences, using an avidin peroxidase revealing system and evaluated with a semiquantitative scoring method. The results of binding of these lectins have been compared with those seen in the resection margins of (at least 5 cm away from) colorectal carcinomas. Consistent regional variations were noted between right- and left-sided colonic tissues, with more diverse glycan structures and a greater sialyl content in the distal colon. There was evidence of graduation of formation of oligosaccharide chains in developing crypts, possibly related to the maturation and expression of glycosyl transferases responsible for the incorporation of mannose residues of N-linked oligosaccharides and of N-acetylgalactosamine and N-acetylglucosamine. Comparison with previous reports has revealed some variations, possibly related to tissue fixation and processing and to lectin concentrations employed, which raises the question of standardization of methodologies in lectin histochemical investigations.

Colon↗
PubMed1994

The histopathological features of asymptomatic hepatitis C virus-antibody positive blood donors.

Since the introduction of screening for hepatitis C virus (HCV) in donated blood, the risk of contracting posttransfusion hepatitis has been greatly reduced and the test has led to the recognition of asymptomatic blood donors positive for anti-HCV antibodies. Following confirmation of the HCV status with second generation RIBA testing followed by counselling, 55 patients had full investigations, including liver biopsy. These were classified by the traditional chronic hepatitis system and were graded according to the Knodell and Scheuer histological activity indices. Seven of the biopsies were normal (12%), apart from minor degrees of steatosis in two. Eleven cases (20%) were in the chronic lobular hepatitis category without portal inflammation, while 37 cases showed portal inflammation, including 20 (36%) cases where chronic persistent hepatitis was the predominant feature and 17 cases (31%) where there was chronic active hepatitis with piecemeal necrosis. Features which have previously been described in chronic HCV-associated hepatitis were noted: portal lymphoid aggregates (58%), lymphoid follicles with germinal centres (15%), bile duct damage (11%), lobular inflammation (80%), sinusoidal mononuclear cell infiltration (26%), acidophil body formation (11%), and steatosis (47%). Fibrosis was present in 46% of cases but was generally of mild degree; 9% of biopsies demonstrated bridging fibrosis but no cases of cirrhosis were present. Even though serum transaminase levels correlated well with the presence of chronic hepatitis and with the Scheuer and Knodell activity indices, a proportion of patients with significant liver damage had normal transaminase levels, and this study suggests the need for liver biopsy in the evaluation of asymptomatic HCV-positive blood donors.

Alanine Transaminase↗