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Biomedical subjects

R C Williamson

Publications and source records attributed to R C Williamson.

At least 91 records · Page 5Linked to original sources
PubMed1992

Duodenogastric reflux enhances growth and carcinogenesis in the rat pancreas.

Surgery for peptic ulcer disease may increase the risk of pancreatic cancer. The effect of duodenogastric reflux on pancreatic carcinogenesis was tested, and changes in the circulating levels of cholecystokinin (CCK) and gastrin were measured. Male Wistar rats (n = 40) weighing 250-300 g were randomized to undergo gastrotomy (control) or split gastrojejunostomy (to produce complete duodenogastric reflux) and then to receive azaserine (30 mg/kg/week intraperitoneally) or saline injections for 3 weeks. At 6 months, blood CCK was assayed and the pancreas was excised for quantitative estimation of atypical acinar cell foci (AACF), the precursor lesions of carcinoma. Rats that had undergone split gastrojejunostomy weighed 15-19 per cent less than controls (P < 0.05), but their relative pancreatic weight (mg pancreas per 100 g body-weight) was 52-60 per cent greater (P < 0.001). Acidophilic AACF occurred only in azaserine-treated rats with duodenogastric reflux. Although plasma CCK concentrations were unchanged, split gastrojejunostomy increased basal and postprandial gastrin levels by 98-175 per cent (P < 0.05). Duodenogastric reflux produces sustained hypergastrinaemia and promotes experimental pancreatic carcinogenesis.

Anastomosis, Surgical↗
PubMed1992

The effect of dietary calcium supplementation on intestinal lipid metabolism.

Population studies in man and experimental animal work support the contention that dietary supplementation with calcium may prevent the development of colorectal cancer. The mechanism of action is postulated to be bile acid chelation in the small-bowed forming non-toxic calcium soap compounds but such substances have yet to be isolated and quantified. In this 2-part study faecal concentrations of acidic lipids and neutral sterols were measured in 93 Sprague-Dawley rats whose calcium intake was modulated by enriching the chow and adding calcium lactate (24 milligrams) to the drinking water. In study-1 (dietary calcium intake doubled from 0.4-0.8%) small bowel resection was used to manipulate colonic lipid concentration for comparison with control rats who had undergone transection with immediate restoration of bowel continuity at an equivalent point. Faecal concentrations of free bile acids were 53-67% less in animals receiving added calcium [1.76 +/- 1.33 vs 0.82 +/- 0.65 mg/g (transection); 2.74 +/- 3.73 vs 1.03 +/- 1.27 mg/g (small bowel resection): P less than 0.001]. In study-2 (dietary calcium intake trebled to 1.21%) faecal bile acid concentration was reduced by 32% (1.86 +/- 0.57 vs 1.27 +/- 0.34 mg/g: NS) whereas long chain fatty acid concentrations were increased by 117% (6.77 +/- 2.39 vs 14.67 +/- 4.82 mg/g: P less than 0.001) in animals receiving added calcium. Serum calcium levels remained unchanged in these animals. Calcium soaps of the bile acids were not detected in faeces and therefore contrary to popular theory these results indicate that conditions within the intestinal lumen favour calcium chelation of long chain fatty acids rather than bile acids.

Animals↗
PubMed1992

Loss of heterozygosity on chromosomes 1 and 11 in carcinoma of the pancreas.

Little is known of the molecular-genetic changes in carcinoma of the pancreas (CaP). In order to investigate the allele loss, or loss of heterozygosity (LOH), in CaP, we studied 13 patients with exocrine CaP and two with endocrine CaP using restriction fragment length polymorphism analysis. Twenty probes assigned to chromosomes 1, 5, 7, 9, 11, 12, 13, 14, 16, 17 and 18 were used. The frequency of LOH, or fractional allele loss (FAL), was found in two endocrine tumours to be 0.333 and 0.455 respectively; and FAL in 13 oxocrine tumours ranged from 0 to 0.25. Allele loss was shown in both exocrine and endocrine tumours by the probes Lambda MS1 at 1p33-35, and pMS51 at 11q13. Probes for other chromosomes have as yet shown no consistent LOH. In conclusion, the study showed LOH on chromosomes 1 and 11 in both exocrine and endocrine CaP.

Carcinoma↗
PubMed1992

Enhancing effect of partial gastrectomy on pancreatic carcinogenesis.

The controversial issue of enhanced pancreatic carcinogenesis following partial gastrectomy has been explored in male Wistar rats (n = 40) weighing 250-300 g. Animals were randomised to receive either 60% distal gastrectomy with Roux-en-Y reconstruction or gastrotomy and resuture (control). Immediately after operation each group was further divided into two subgroups, receiving i.p. injections of either saline or azaserine (30 mg kg-1 wk-1 for 3 weeks). At 15 months blood was obtained at 0, 5, 15 and 30 min after a fatty meal for cholecystokinin (CCK) assay; rats were then killed. Pancreatic wet weight was measured, and histological sections were examined for atypical acinar cell foci (AACF), the putative precursor lesion of carcinoma. There were no significant differences in body weight or pancreatic weight between controls and rats with gastrectomy. Only azaserine-treated rats had acidophilic AACF. Partial gastrectomy substantially increased the number of acidophilic AACF per pancreas (median 26.05 vs 2.09; P less than 0.005), with a 9-fold increase in their volume (P less than 0.005). Basal and postprandial plasma CCK concentrations were higher after gastrectomy than in controls (P less than 0.05). Partial gastrectomy has an enhancing effect on azaserine-induced pancreatic carcinogenesis, probably by means of increased CCK release.

Anastomosis, Roux-en-Y↗
PubMed1992

Pancreatic exocrine and endocrine function after operations for chronic pancreatitis.

Exocrine and endocrine function of the pancreas was assessed in the early postoperative period (< or = 2 months) and subsequently (mean, 25 months; range, 3 to 120) in 103 patients (69 men, 34 women; mean age, 42.4 +/- 11.6 years) undergoing operation for chronic pancreatitis. Alcohol was the main causative agent (69%) and pain the most frequent indication (87%) for operation. Drainage procedures (n = 23) did not alter pancreatic function either initially or on long-term follow-up. In the early postoperative period, distal pancreatectomy (n = 42) often impaired endocrine function without affecting exocrine function; seven patients (17%) became diabetic, and results of oral glucose tolerance test showed deterioration in 23 of 28 patients (82%, p < 0.05). On subsequent follow-up, 11 patients developed exocrine failure (p < 0.01) and 10 patients endocrine (p < 0.01) failure. Proximal pancreatectomy (n = 38) precipitated clinical exocrine failure in 14 patients (37%, p < 0.01), yet pancreolauryl tests in 18 patients showed little objective change in exocrine status (0.50 > p > 0.10). Endocrine function was initially spared after proximal pancreatectomy, but six additional patients (16%, p < 0.05) required treatment for diabetes at a mean of 19 months (range, 3 to 34). Deterioration in pancreatic function is thus not an invariable immediate consequence of pancreatic drainage procedures or partial pancreatectomy for chronic pancreatitis. Progression of disease must account, in part, for failure of both exocrine and endocrine function on long-term follow-up. Drainage operations appear to delay this progressive decline in pancreatic function.

Adolescent↗
PubMed1992

Vitamin D and its metabolites inhibit cell proliferation in human rectal mucosa and a colon cancer cell line.

Like calcium, vitamin D may protect against colorectal neoplasia as it reduces epithelial cell proliferation and induces differentiation. Although its therapeutic use is limited by its effects on calcium metabolism, analogues such as calcipotriol produce little hypercalcaemia. Stathmokinetic and immunohistochemical techniques were used to study the effect of 1,25 (OH)2 D3 and its analogues on cell proliferation in human rectal mucosa and a colon cancer cell line. Paired sigmoidoscopic biopsy specimens were obtained from 17 control patients and five patients with familial adenomatous polyposis. Explants were established in organ culture, with or without the addition of vitamin D. Proliferation was assessed using (1) metaphase arrest to determine the crypt cell production rate (CCPR) and (2) Ki-67 monoclonal antibody directed against an antigen present in proliferating cells. 1,25 (OH)2 D3 in concentrations of 1 microM-100 pM (10(-6)-10(-10) M) reduced the CCPR (cells/crypt/hour) from 4.74 to 2.15-2.67 (p < 0.001), and the Ki-67 labelling index from 7.28-3.74 (p < 0.01). Likewise, vitamin D2, 10 nM (10(-8) M) reduced the CCPR from 4.74-2.74 (p < 0.05) and calcipotriol from 4.86-2.38 (p < 0.05). In familial adenomatous polyposis patients 1,25 (OH)2 D3 100 pM (10(-10) M) halved the CCPR from 8.75-4.22. Calcipotriol (10(-5) M to 10(-9) M) produced a clearcut dose response inhibition of HT-29 cell growth. Thus, vitamin D and its metabolites inhibit proliferation in normal and premalignant rectal epithelium and suppress growth in a colorectal cancer cell line.

Adenomatous Polyposis Coli↗
PubMed1992

Role of cholecystokinin in pancreatic adaptation to massive enterectomy.

Since pancreatic adaptation to massive proximal small bowel resection (PSBR) may be modulated through cholecystokinin (CCK) secretion, we tested the effect of the CCK antagonist CR-1409 on this response. Male Wistar rats (n = 72) weighing 220-225 g were randomised to receive either PSBR or transection/resuture followed by saline or CR-1409 (12 mg/kg daily subcutaneously). Rats were killed one, two, and three weeks post-operatively, at which time blood was obtained for CCK assay and the pancreas was assessed for proliferative activity by three parameters: nucleic acid and protein content, bromode-oxyuridine (BrdUrd) labelling index, and proliferating cell nuclear antigen (PCNA) expression. PSBR increased plasma CCK concentration by 83-102% at 1-3 weeks, irrespective of CR-1409 administration. Total pancreatic DNA content per 100 g body weight increased by 34% at two weeks (p less than 0.05) and by 82% at three weeks (p less than 0.05), while RNA content increased by 60% and 178% (p less than 0.001) and protein content by 20% and 57% (p less than 0.05). PSBR increased the BrdUrd labelling index and the percentage of PCNA immunoreactive cells. CR-1409 completely abolished this proliferative response and also prevented the rise in nucleic acid and protein contents. Apart from growth stimulation, PSBR also enhanced pancreatic exocrine function, as shown by ultrastructural evidence of an appreciable decrease in zymogen granules; CR-1409 also inhibited this functional effect of hypercholecystokininaemia. The results confirm the tropic role of CCK after PSBR, and CR-1409 prevents this pancreatic adaptation.

Animals↗
PubMed1992

Iodostearic acid in the treatment of advanced gastrointestinal carcinoma.

This phase II non-comparative trial evaluated the efficacy of intramuscular iodostearic acid in the treatment of 30 patients with advanced carcinoma of the gastrointestinal tract. These included 17 patients with colorectal carcinoma, seven with pancreatic carcinoma, four with gastric carcinoma, one with hepatocellular carcinoma and one with cholangiocarcinoma. Iodostearic acid emulsion (2 ml/1.2 g) followed by depomedrone (0.5 ml/10 mg) was injected intramuscularly twice weekly. No serious toxic effects were observed, the main side effects being local pain at the injection site and hot flushes. There were no partial or complete responses. Stable disease was seen in six of 30 patients (20%) at 3 months and three of 30 patients (10%) at 6 months. In conclusion, intramuscular iodostearic acid is relatively non-toxic, however, it appears to be of little value in the treatment of patients with advanced gastrointestinal carcinomas.

Adenocarcinoma↗
PubMed1992

Evaluation and surgical correction of esophagitis after partial gastrectomy.

Among 51 patients with refractory symptomatic reflux esophagitis seen during an 18-month period, 8 (16%) had undergone previous partial gastrectomy. Either Billroth II (n = 6) or Billroth I (n = 2) resection had been carried out for peptic ulceration 18 months to 30 years beforehand. Each patients was evaluated by symptom scoring, endoscopy, and 24-hour pH monitoring plus a 16-hour esophageal aspiration study, in which 2-hourly aliquots were measured for acid, pepsin, conjugated and unconjugated bile acids, and trypsin. After conversion to a 45 cm Roux-en-Y gastroenterostomy, symptom scoring and endoscopy were repeated at 6 to 12 months in all eight patients. Pepsin, acid, and unconjugated bile acids were seldom present in esophageal aspirates. Conjugated bile acids in concentrations up to 30 mmol/L and trypsin up to 428 micrograms/ml were found in cases of severe esophagitis, mostly during nocturnal rest. Esophagitis, heartburn, regurgitation, and bilious vomiting were eradicated by Roux-en-Y conversion, but other postgastrectomy symptoms (early satiety, dumping, epigastric pain, and diarrhea) were largely unchanged. Postgastrectomy esophagitis resistant to medical therapy seems likely to be caused by nocturnal exposure to trypsin and conjugated bile acids; it is well controlled by a 45 cm Roux-en-Y conversion.

Aged↗
PubMed1992

Injury to the superior mesenteric artery during pancreatectomy for chronic pancreatitis.

Four cases are described of injury to the superior mesenteric artery (SMA) during pancreatectomy for chronic pancreatitis. Review of the literature indicates that this is a rare event. In three patients (arterial ligation, 2; haemorrhage, 1), the injury was immediately recognised and successfully repaired. In the fourth (with probable occlusion of the vessel), the problem was not appreciated at operation and the patient eventually died. Vessels adherent to a pseudocyst are at particular risk of injury, as in two of our patients. Two patients had ectopic origin of the right hepatic artery. Since awareness of such vascular anomalies is important, we now perform selective mesenteric angiography in all patients requiring pancreatic resections, whether proximal or distal.

Adult↗
PubMed1991

Tropic role of enteroglucagon in pancreatic adaptation to subtotal enterectomy.

Proximal small bowel resection causes pancreatic hyperplasia, presumably via a humoral mechanism. Although cholecystokinin can stimulate pancreatic growth, its proximal distribution in the gut makes it an unlikely intermediary after proximal small bowel resection. The potential roles of neurotensin and enteroglucagon were studied, since these hormones are mainly secreted from the ileum and proximal colon. Male Wistar rats (n = 50) weighing 200-250 g were randomized to receive 90 per cent proximal small bowel resection or jejunal transection and resuture (control). Rats were killed at 1 week or 1 month, when plasma was obtained for hormone assay and the pancreas was excised for protein and nucleic acid measurement. Proximal small bowel resection increased circulating enteroglucagon levels by 150 per cent at 1 week (P less than 0.002) and by 83 per cent at 1 month (P less than 0.005); neurotensin levels were unchanged. Pancreatic wet weight was 21 per cent greater 1 month after proximal small bowel resection (P less than 0.001). Proximal small bowel resection increased protein, RNA and DNA contents of the pancreas both at 1 week and at 1 month. Since plasma enteroglucagon correlated with these indices of pancreatic mass, enteroglucagon may have a pancreatotropic role (in addition to its enterotropic role).

Adaptation, Physiological↗
PubMed1991

Distal pancreatectomy with and without splenectomy.

Splenectomy is performed routinely during distal pancreatectomy, yet the spleen has an important role in host defence and can often be preserved. A personal series of 100 distal pancreatectomies undertaken for pancreatic disease between 1978 and 1990 included 23 patients undergoing total pancreatic resection. The remaining 77 patients, who form the basis of the present report, underwent primary distal pancreatectomy and comprised 34 women and 43 men with a median age of 41 years (range 17-78 years). Conventional distal pancreatectomy including splenectomy was performed in 42 patients (55 per cent) for chronic pancreatitis (34 patients), pancreatic neoplasia (six patients), suspected pancreatitis (one patient) or pancreatitic trauma (one patient). Conservative resection with splenic preservation was performed in 35 patients (45 per cent) for chronic pancreatitis (12 patients), suspected pancreatitis (13 patients, including eight patients with pancreas divisum), pancreatic neoplasia (six patients), recurrent acute pancreatitis (two patients) and pancreatic trauma (two patients). There were no postoperative deaths in either group. Early complications followed conventional resection in 10 patients (24 per cent) and conservative resection in seven patients (20 per cent). In five patients the splenic vessels were ligated away from the splenic hilum and the spleen was left in situ, but subsequent isotope scans and haematological indices showed no hyposplenism. The spleen can safely be preserved in many distal pancreatic resections, including those for inflammatory disease, and we now prefer a retrograde technique for dissecting the pancreas off the splenic vessels.

Adolescent↗
PubMed1991

Pancreatic tissue and ductal pressures in chronic pancreatitis.

To assess the contribution of parenchymal hypertension to pain, pancreatic tissue pressures were measured intraoperatively in 17 patients with chronic pancreatitis and in four other patients undergoing pancreatic surgery (reference group). The technique involved direct fine needle cannulation of the pancreas using a flow infusion system, which measured parenchymal resistance to this infusion. Three to six recordings were obtained at each site. In chronic pancreatitis the pressure (mean +/- s.e.m.) was substantially elevated in all regions of the pancreas compared with reference subjects: head (257 +/- 59 versus 19 +/- 5 mmHg, P less than 0.05); body (201 +/- 51 versus 13 +/- 6 mmHg, P less than 0.05) and tail (161 +/- 45 versus 11 +/- 3 mmHg, P less than 0.05). Elevation was greater in areas of calcific disease (281-383 mmHg) than in non-calcific disease (81-120 mmHg, P less than 0.05). Mean pancreatic ductal pressure in 10 patients (seven with calcific disease) was 20 +/- 4 mmHg. Differential pressure measurements within the pancreas helped determine the extent of resection in six patients with diffuse disease. The greatly increased tissue pressures in chronic pancreatitis, especially in the presence of calcification, suggest a possible 'compartment syndrome'.

Adult↗