Biomedical subjects

C J Shields

Publications and source records attributed to C J Shields.

5 recordsLinked to original sources

PubMed2004

Perioperative topical nitrate and sphincter function in patients undergoing transanal stapled anastomosis: a randomized, placebo-controlled, double-blinded trial.

PURPOSE: The use of transanal stapling devices may impair continence because of digital dilatation and/or instrumentation. This study assessed the effect of pharmacological dilatation of the sphincter prior to stapler insertion. METHODS: A randomized, placebo-controlled, double-blinded study of 60 patients undergoing transanal stapled anastomosis was undertaken. Consenting patients were randomly assigned to receive a single intraoperative dose of topical 0.2 percent nitroglycerin (glyceryl trinitrate) ointment or nitroglycerin-free placebo. All patients were assessed preoperatively and postoperatively by clinical methods (Wexner incontinence scores and examination), anorectal manometry by a station pull-through technique, and endoanal ultrasonography. RESULTS: Intraoperative mean (+/-SEM) resting pressures (mmHg) were significantly reduced by nitroglycerin compared with prenitroglycerin levels (9.9 +/- 0.9 vs. 50.5 +/- 2.7; P = 0.002) or controls (56.0 +/- 3.2; P = 0.001). Twenty-one of the 28 controls (75 percent) but only 4 of the 32 patients in the nitroglycerin group (12.5 percent) required digital dilatation to insert the stapling instrument ( P = 0.003). Squeeze pressures were unaltered by the intervention but mean resting pressures were higher in the nitroglycerin group postoperatively (52.9 +/- 3.2 - 31.6 +/- 1.3 = 21.3 mmHg; 95 percent confidence interval, 14-27). Incontinence scores were lower in the nitroglycerin group at the 3-month (1.1 +/- 0.2 vs. 4.6 +/- 0.3; P = 0.003) and 12-month (0.9 +/- 0.1 vs. 4.4 +/- 0.3; P = 0.002) clinic visits. CONCLUSION: Preoperative nitroglycerin dilatation protects sphincter function in patients undergoing transanal stapled anastomoses.

Administration, Topical↗

PubMed2001

Desmoid tumours.

Desmoid tumours exhibit fibroblastic proliferation and arise from fascial or musculoaponeurotic structures. Despite their benign microscopic appearance, and their negligible metastatic potential, the propensity of desmoid tumours for local infiltration is potentially significant in terms of deformity, morbidity and mortality due to pressure effects and obstruction of vital structures and organs. The rarity of desmoid tumours, coupled with the variability in their clinical course, renders these lesions a vexing entity, and makes demonstration of the efficacy of any specific intervention difficult. Failure to recognize the potential for malignant behaviour in this tumour renders desmoids susceptible to inadequate treatment. This distinct pathological entity is reviewed with a specific focus on aetiology and treatment.

Antineoplastic Agents, Hormonal↗

PubMed2001

Attenuation of pancreatitis-induced pulmonary injury by aerosolized hypertonic saline.

BACKGROUND: The immunomodulatory effects of hypertonic saline (HTS) provide potential strategies to attenuate inappropriate inflammatory reactions. This study tested the hypothesis that administration of intratracheal aerosolized HTS modulates the development of lung injury in pancreatitis. METHODS: Pancreatitis was induced in 24 male Sprague-Dawley rats by intraperitoneal injection of 20% L-arginine (500 mg/100 g body weight). At 24 and 48 h, intratracheal aerosolized HTS (7.5% NaCl, 0.5 mL) was administered to 8 rats, while a further 8 received 0.5 mL of aerosolized normal saline (NS). At 72 hours, pulmonary neutrophil infiltration (myeloperoxidase activity) and endothelial permeability (bronchoalveolar lavage and wet:dry weight ratios) were assessed. In addition, histological assessment of representative lung tissue was performed by a blinded assessor. In a separate experiment, polymorphonucleocytes (PMN) were isolated from human donors, and exposed to increments of HTS. Neutrophil transmigration across an endothelial cell layer, VEGF release, and apoptosis at 1, 6, 12, 18, and 24 h were assessed. RESULTS: Histopathological lung injury scores were significantly reduced in the HTS group (4.78 +/- 1.43 vs. 8.64 +/- 0.86); p < 0.001). Pulmonary neutrophil sequestration (1.40 +/- 0.2) and increased endothelial permeability (6.77 +/- 1.14) were evident in the animals resuscitated with normal saline when compared with HTS (0.70 +/- 0.1 and 3.57 +/- 1.32), respectively; p < 0.04). HTS significantly reduced PMN transmigration (by 97.1, p = 0.002, and induced PMN apoptosis (p < 0.03). HTS did not impact significantly upon neutrophil VEGF release (p > 0.05). CONCLUSIONS: Intratracheal aerosolized HTS attenuates the neutrophil-mediated pulmonary insult subsequent to pancreatitis. This may represent a novel therapeutic strategy.

Acute Disease↗

PubMed2000

Hypertonic saline attenuates end-organ damage in an experimental model of acute pancreatitis.

BACKGROUND: Hypertonic saline (HTS) has been noted previously to reduce neutrophil activation. The aim of this study was to elucidate the effect of hypertonic resuscitation on the development of end-organ damage in an animal model of pancreatitis. METHODS: Pancreatitis was induced in Sprague-Dawley rats by intraperitoneal injection of 20 per cent L-arginine. Animals were randomized into four groups (each n = 8): controls; pancreatitis without intervention; pancreatitis plus intravenous resuscitation with normal saline (0.9 per cent sodium chloride 2 ml/kg) at 24 and 48 h; or HTS (7.5 per cent sodium chloride 2 ml/kg) at these time points. Pulmonary endothelial leakage was assessed by measurement of lung wet : dry ratios, bronchoalveolar lavage protein and myeloperoxidase activity. RESULTS: Animals that received HTS showed less pancreatic damage than those resuscitated with normal saline (1.0 versus 3.0; P = 0.04). Lung injury scores were also significantly diminished in the HTS group (1.0 versus 3.5; P = 0.03). Pulmonary neutrophil sequestration (myeloperoxidase activity 1.80 units/g) and increased endothelial permeability (bronchoalveolar lavage protein content 1287 microgram/ml) were evident in animals resuscitated with normal saline compared with HTS (1.22 units/g and 277 microgram/ml respectively; P < 0.02). CONCLUSION: HTS resuscitation results in a significant attenuation of end-organ injury following a systemic inflammatory response to severe pancreatitis.

Animals↗

PubMed1998

No difference in stem cell somatic mutation between the background mucosa of right- and left-sided sporadic colorectal carcinomas.

Epidemiological, morphological, and molecular differences exist between carcinomas of the right and left sides of the large bowel. To investigate whether this is reflected in differences in somatic mutation frequency in the background mucosa, mutation of the neutral O-acetyltransferase gene (oat) was quantified in histologically normal resection margins from 20 informative (heterozygous) patients with caecal or ascending colon cancer (11 males, median age 75 years) and 20 with sigmoid colon or rectal cancer (10 males, median age 70 years). Mutant discordant crypts lacking O-acetyltransferase activity were visualized by mPAS staining and classified as wholly or partially involved by the mutant phenotype; median frequencies (x10(-4) were compared (Mann-Whitney U-test) after assessing a sample of more than 10,000 crypts per case. No significant difference was found between the frequencies of wholly involved mPAS-positive crypts in background mucosa of left- and right-sided cancers (p = 0.4569), indicating that tumours on both sides of the colon are associated with similar levels of lifetime-accumulated stem cell mutational load. However, partially involved mPAS-positive crypts were significantly more frequent in mucosa from left-sided cancers (p < 0.04), indicating increased mutational activity during the previous 12 months. Analysis of mucosa proximal and distal to left-sided cancers showed that this increase was due to a statistically higher frequency of partially involved crypts in proximal mucosa, which probably resulted from the obstructive effects of the tumour causing increased exposure of the proximal mucosa to luminal carcinogens and/or epithelial regeneration in response to low-grade inflammation or ischaemia. The findings indicate that although left-sided colonic cancer is commoner than right-sided cancer in the British population, carcinomas on both sides of the large bowel arise in a background of similar levels of stem cell mutational activity.

Acetyltransferases↗