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Biomedical subjects

R C Williamson

Publications and source records attributed to R C Williamson.

At least 19 recordsLinked to original sources
PubMed1995

Extrinsic-pathway activation in cancer with high factor VIIa and tissue factor.

Thromboembolic complications are common in patients with malignant disease. We studied the activation of coagulation in 106 patients with solid tumours and 72 healthy volunteers by measuring plasma levels of tissue factor, factor VIIa, factor XIIa, thrombin-antithrombin complex, and prothrombin fragments 1 + 2. Tissue factor was 67% higher in cancer patients (median 582 vs 349 pg/mL, p = 0.0006) and factor VIIa was 46% higher (100 vs 69 mU/mL, p = 0.0002), indicating extrinsic pathway activation. Modest activation of the intrinsic pathway (elevated factor XIIa) was seen only in patients with advanced disease or those receiving chemotherapy. Excess thrombin generation was manifested by elevations in thrombin-antithrombin complex and prothrombin fragments 1 + 2. Tissue factor pathway is clearly implicated in the hypercoagulable state of cancer.

Blood Coagulation↗
PubMed1995

Enhanced intra-anastomotic healing by operative lavage with nutrient solutions in experimental left-sided colonic obstruction.

The influence of intraoperative lavage with various solutions was tested on the healing of experimental colonic anastomoses performed in the presence of obstruction. After 24 h of ligature obstruction to the pelvic colon, male Wistar rats (n = 108) underwent colonic resection and primary anastomosis, using lavage with one of four different fluids: saline, povidone-iodine, 10 per cent hypertonic glucose and short-chain fatty acids (SCFA). Controls had no lavage. The anastomotic segment was excised and studied after 3 or 6 days. At day 3, mean(s.d.) bursting pressure was significantly greater in animals receiving SCFA compared with controls (81.2(23.0) mmHg versus 34.8(34.0) mmHg). Mean(s.d.) bowel wall tension was higher in rats with SCFA (30.6(8.1) N/m x 10(-4) or hypertonic glucose (29.5(10.1) N/m x 10(-4) compared with controls (12.2(12.1) N/m x 10(-4). By day 6, the anastomosis was more resistant to intraluminal pressure in each lavage group; mean(s.d.) hydroxyproline concentration at the anastomosis was greater in rats with SCFA (12.4(1.5) micrograms/mg) or hypertonic glucose (11.6(2.9) micrograms/mg) than in controls (8.9(1.5) micrograms/mg). Anastomotic healing is improved by all types of intraoperative colonic lavage, particularly with SCFA and hypertonic glucose solutions.

Anastomosis, Surgical↗
PubMed1995

Tissue factor expression correlates with histological grade in human pancreatic cancer.

The transmembrane cellular receptor tissue factor (TF) is the primary initiator of the coagulation cascade in man. Expression of TF was determined in 55 specimens of ductal adenocarcinoma of the pancreas and was found to correlate strongly with the degree of histological differentiation. A significant linear trend was observed with stronger immunoreactivity observed in poorly differentiated tumours (chi 2 = 6.69, P = 0.0098). No TF staining was seen in pancreatic samples from normal controls (n = 18). As expression of TF may be associated with tumour progression, its analysis could provide useful prognostic information in patients with pancreatic malignancy.

Adult↗
PubMed1995

Role of total pancreatectomy in the treatment of patients with end-stage chronic pancreatitis.

Forty patients underwent total pancreatoduodenectomy for end-stage chronic pancreatitis. There were 34 men and six women of median age 39 (range 21-66) years. Alcoholism was the major aetiological agent (30 patients), and five patients had had previous acute idiopathic pancreatitis. The overwhelming indication for operation was severe abdominal pain, complicated by failing exocrine and endocrine function. Resection was performed in one (17 patients) or two (23) stages, following previous proximal (seven) or distal (16) pancreatectomy; progression from partial to total pancreatectomy occurred over an interval of 8-96 (median 15) months. A further six patients had undergone previous pseudocyst or duct drainage procedures. The pylorus was preserved in 28 patients and the spleen in ten. Median operating time was 6 (range 2.5-8.5) h and median blood loss 2000 (range 500-16,000) ml. There were two hospital deaths and three patients required reoperation. Of 38 survivors, 30 obtained complete or substantial relief of pain. There were 15 late deaths at 2.5-120.0 months after operation, 13 in the alcohol group and 11 disease-related. Total pancreatectomy can relieve the intractable pain of chronic pancreatitis at the cost of possible premature death from continuing alcohol abuse.

Abdominal Pain↗
PubMed1995

Expression of transforming growth factor-beta 1 in chronic pancreatitis.

Transforming growth factor-beta 1 (TGF-beta 1) is a multifunctional cytokine which modifies tissue stromal matrix synthesis, cell proliferation and immune function. In the present study, we have used a mouse monoclonal antibody to the latent (intracytoplasmic) form of TGF-beta 1 to compare its expression in 144 cases of human chronic pancreatitis (both obstructive and chronic calcifying) with that of 10 control pancreatic specimens. In all the control specimens, and most of those with chronic pancreatitis, cytoplasmic immunoreactivity was identified in pancreatic duct and ductular epithelium, in islet cells and in vascular smooth muscle and endothelium. Two distinct patterns of ductular epithelial staining emerged: in morphologically normal tissues, only individual distal ductular/centroacinar cells stained but in chronic pancreatitis (whether chronic calcifying or chronic obstructive) the staining was panductular. Positive cytoplasmic immunostaining of acinar epithelial cells was found in 3% of pancreatitis specimens but in none of the normal controls. There was no staining of fibroblasts. Synthesis of TGF-beta 1 appears to be normally restricted to a population of epithelial cells located in terminal/centroacinar regions of the ductules (together with occasional ductal cells) whereas in chronic pancreatitis, TGF-beta 1 is expressed in most ductular and ductal epithelial cells.

Case-Control Studies↗
PubMed1994

Localization and surgical management of insulinoma.

Over a 14-year period 34 patients were referred for surgical treatment of insulinoma. The diagnosis was confirmed by demonstrating hypoglycaemia with inappropriate hyperinsulinaemia during prolonged fasting. Selective visceral angiography localized 30 solitary benign insulinomas and two carcinomas. In two patients with islet cell hyperplasia, angiography demonstrated a single lesion only. Ultrasonography had a sensitivity of 15 per cent and computed tomography a sensitivity of 24 per cent in the localization of tumours. All patients but one were treated by operation. Eighteen tumours were enucleated and 13 (including both patients with islet cell hyperplasia) were treated by distal pancreatectomy. Two patients underwent negative primary exploration; both had single adenomas removed at re-exploration. There were no operative deaths but nine patients (predominantly those undergoing pancreatic resection) had complications. Thirty-one patients were symptom-free following operation at a mean follow-up of 16 months.

Adolescent↗
PubMed1994

Surgical treatment of primary duodenal carcinoma: a personal series.

In a personal series, 22 patients (11 men, 11 women) of median age 60 (range 25-81) years with primary duodenal adenocarcinoma underwent operation between 1979 and 1993. Tumours arising from bile duct, ampullary or pancreatic tissue were excluded. Principal presenting symptoms were jaundice (12 patients), pain (seven), anaemia (six) and vomiting (six). A pre-existing villous adenoma was seen in 11 patients and adjacent duodenal dysplasia in 13. Sites of origin were mostly the second part of the duodenum (18 patients) but also the third and fourth parts (two each). Seventeen patients underwent 'curative' resection with one hospital death at 25 days; the 5-year survival rate thereafter was 40 per cent. Five patients who received palliative surgery survived for a median of 7 months. Primary duodenal carcinoma is a distinct entity with a better prognosis than pancreatic cancer after radical resection. It favours the descending duodenum and is closely linked with villous adenoma and epithelial dysplasia.

Adenocarcinoma↗
PubMed1994

Calcipotriol inhibits rectal epithelial cell proliferation in ulcerative proctocolitis.

Vitamin D3 reduces human rectal crypt cell production rate (CCPR) and may thereby protect against colorectal cancer. Cell turnover is increased in ulcerative proctocolitis, which might therefore respond to vitamin D3 metabolites. This study investigated the effect of calcipotriol, a synthetic vitamin D3 analogue that avoids hypercalcaemia, on human rectal CCPR in ulcerative proctocolitis. Paired rectal biopsy specimens from seven patients with severe disease were established in organ culture with or without calcipotriol (1 x 10(-6) M). After 15 hours, vincristine (0.6 microgram/ml) was added to induce metaphase arrest, and CCPR was determined by linear regression analysis of accumulated metaphases. Compared with values in 17 controls with incidental anal conditions, median rectal CCPR was 28% higher in ulcerative proctocolitis: 5.90 (5.00-9.50) v 4.80 (2.85-7.07) cells/crypt/hour (p < 0.01). Calcipotriol reduced CCPR by 62% in patients with ulcerative proctocolitis, from 5.90 (5.00-9.50) to 2.21 (0.81-3.22) cells/crypt/hour (median with range) p < 0.01. Thus calcipotriol can dampen the hyperproliferative state in ulcerative proctocolitis and could have a therapeutic role in the control of this inflammatory condition.

Adult↗
PubMed1994

Divergent effects of epidermal growth factor and calcipotriol on human rectal cell proliferation.

Vitamin D may protect against colorectal cancer by reducing cell proliferation and inducing differentiation. By contrast, epidermal growth factor (EGF) stimulates cell proliferation and may encourage gastrointestinal mucosal healing. This study investigated the effect of a synthetic vitamin D analogue, calcipotriol, and EGF on human rectal epithelial cell proliferation in patients with familial adenomatous polyposis (FAP). In addition, a new technique to measure the cell cycle time is described. Sigmoidoscopic biopsy specimens were obtained from 14 patients with FAP. Tissue was established in organ culture, with or without the addition of EGF (n = 8), or calcipotriol (n = 6). Proliferation was determined using (a) metaphase arrest to measure the crypt cell production rate, (b) native mitotic index, and (c) the growth fraction using PC10 antibody. EGF receptor expression was shown using a polyclonal antibody AP12E. Calcipotriol reduced crypt cell production rate by 52% from mean (SEM) 5.29 (1.18) to 2.56 (0.80) cells/crypt/hour (p < 0.01) and EGF increased crypt cell production rate by 102% from 3.62 (0.59) to 7.33 (0.90) cells/crypt/hour (p < 0.05), and this tissue expressed the EGF receptor. The growth fraction was 48.40 (4.0)%, and the native mitotic index 1.08 (0.14)%. The cell cycle time was estimated as 94.5 hours and the time for mitosis as one hour. Thus, calcipotriol and EGF have divergent effects on human rectal mucosal proliferation.

Adenomatous Polyposis Coli↗