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Biomedical subjects

R C Williamson

Publications and source records attributed to R C Williamson.

At least 163 records · Page 9Linked to original sources

Increased activity of digestive enzymes in ileal enterocytes adapting to proximal small bowel resection.

The ability of adapting ileal enterocytes to express different digestive enzymes in their brush border membranes was tested in young female Wistar rats (n = 72) receiving 60% proximal small bowel resection. In control rats with intestinal transection both neutral aminopeptidase and alpha-glucosidase activities were shown, by quantitative cytochemistry, to increase during enterocyte migration over the lower part of the villus; thereafter enzyme activities declined or remained approximately constant. Proximal enterectomy increased the amount of alpha-glucosidase but not neutral aminopeptidase activity appearing during early enterocyte development. Thymidine labelled autoradiography showed that the rate of enterocyte migration along the ileal villus nearly doubled after jejunal resection (19.3 v 11.1 microns/h). Nevertheless, the time taken for both peptidase and saccharidase activities to appear at maximal rates in the brush border membrane was diminished by about five hours. Thus ileal enterocytes adapt to proximal small bowel resection by selective increments in enzyme expression, findings that contradict the previous hypothesis of simple metabolic immaturity.

Aminopeptidases↗

Proximal enterectomy provides a stronger systemic stimulus to intestinal adaptation than distal enterectomy.

Enteroglucagon has been implicated as a tropic hormone in the control of intestinal adaptation. Because cells producing enteroglucagon are located mainly in the distal small bowel (and colon), ileal resection might be expected to produce less adaptive change than a jejunal resection of equivalent length. This hypothesis was tested in male Sprague-Dawley rats (n = 40) weighing 184.0 +/- 7.3 g and receiving a Thiry-Vella fistula (TVF) of the mid-60% of the small intestine. One group had concomitant resection of the jejunum proximal to the TVF (n = 12), another had resection of the ileum distal to the TVF (n = 13), while controls had a TVF alone (n = 15). When killed 10 days postoperatively rats with ileal resection weighed only 81% of controls (p less than 0.001) and 85% of those with jejunal resection (p less than 0.01). Jejunal resection produced an 81% increase in crypt cell production rate (measured by a stathmokinetic technique) over control values (28.5 +/- 4.2 v 15.8 +/- 2.3 cells/crypt/h: p = 0.025), whereas ileal resection had no demonstrable effect (17.5 +/- 2.3 cells/crypt/h). Adaptive hyperplasia in isolated small bowel is modulated by factors localised to the distal small intestine, enteroglucagon being a plausible candidate.

Adaptation, Physiological↗

Ileal carcinoma and tuberculous ileitis.

A 76 year old woman presented with abdominal pain and weight loss. At laparotomy she was found to have an adenocarcinoma of the ileum arising in a segment of tuberculous ileitis. The possible significance of this association is discussed.

Adenocarcinoma↗

Fulminant ulcerative colitis in late pregnancy and the puerperium.

Four patients underwent emergency colectomy during pregnancy or the puerperium for complications of ulcerative proctocolitis. Three had inactive colitis at conception, while in the fourth the disease started during pregnancy. Three patients required subtotal colectomy and ileostomy for toxic dilatation during the third trimester or within 5 days of delivery, and the fourth underwent proctocolectomy postpartum for intractable colitis. There were no maternal deaths but 2 of 4 infants died. One child weighing 1.4 kg survived vaginal delivery during the 33rd week of pregnancy, 2 weeks after his mother had undergone emergency colectomy.

Acute Disease↗

The malignant potential of colorectal Crohn's disease.

Six patients developed colorectal carcinoma in association with Crohn's disease. The cancer was diagnosed at a mean age of 46 years and a mean 19 years after the onset of Crohn's disease. Five carcinomas arose in the chronically inflamed segment of bowel, while a sixth arose in caecum previously bypassed for Crohn's ileitis. Four carcinomas were mucinous, four presented with fistula and four were treated by complete removal of the large intestine. Three patients have died of residual or recurrent cancer. The data support an aetiological link between Crohn's proctocolitis and carcinoma.

Adenocarcinoma, Mucinous↗

Large bowel cancer in the young.

Eighty-five patients aged 40 or less who presented with colorectal carcinoma over a 32-year period were reviewed. The incidence was 2.5 per cent of all patients with large bowel cancer (n = 3426). Predisposing causes included familial polyposis (eight patients), panprotocolitis (ulcerative, one, Crohn's, one) and irradiation (one), four patients were pregnant, one-third of the patients presented as emergencies, and 43 per cent of these had intestinal obstruction. Five-year survival rates were 41 per cent overall and 59 per cent after "curative" resection. Survival was equivalent both for elective and emergency admission and for mucinous carcinomas (n = 16) and those non-mucinous carcinomas of moderate histological differentiation. Five-year survival rates were poorer when the history was less than three months in duration (20 per cent vs 45 per cent: P = 0.02) and for rectal and rectosigmoid tumours than colonic tumours (31 per cent vs 50 per cent: P = 0.05). Radical resection is indicated when feasible: four of five patients with involvement of adjacent viscera and four of six patients with resectable recurrence survived beyond 10 years. The outcome is similar to that at all ages, any unfavourable pathological features being balanced by improved survival following emergency operations.

Adenocarcinoma↗

The use of CA-50 radioimmunoassay test in diagnosis of urologic malignancy. Tie for second place Jobst award.

Circulating levels of the oncofetal antigen, CA-50, have been used to differentiate benign and malignant disease of the prostate, bladder, and kidney, taking 17 units/ml as the upper limit of normal. All 60 normal subjects and 59 of 61 (97%) patients with benign prostatic hypertrophy had levels below 17 units/ml. The test was positive in 29 of 68 (43%) patients with prostatic carcinoma, including 24 of 34 (75%) with metastases, but only five of 34 (15%) patients without metastases (P less than 0.01). Positivity also correlated with histologic grade: 0 per cent with well-differentiated tumors (n = 8), 33 per cent with moderately differentiated (n = 11), and 66 per cent with poorly differentiated tumors (n = 27). All 14 patients with benign bladder disease had negative values, whereas 13 of 21 (62%) patients with bladder carcinoma had positive. Noninvasive tumors were less likely to give a positive value than invasive tumors (42 vs 89%; P less than 0.05). One of 11 (9%) patients with benign renal conditions was positive as opposed to seven of 15 (47%) patients with renal carcinoma. The overall sensitivity of the CA-50 test for urologic malignancy was 47 per cent and specificity was 97 per cent; moreover, serum levels correlated with stage and grade of disease.

Antigens, Neoplasm↗

Sialomucins at resection margin and likelihood of recurrence in colorectal carcinoma.

Oncogenic transformation of colonic epithelium is accompanied by changes in surface carbohydrate, notably an increased secretion of sialomucins at the expense of the normally predominant sulphomucins. In a multicentre prospective trial the correlation between the presence of sialomucins at the resection margin and the subsequent development of local recurrence was studied in 250 patients who had undergone "curative" resection for colorectal carcinoma with a mean follow up period of 14 months. Nineteen of 70 patients (27.1%) with a sialomucin predominant pattern at either resection margin developed local recurrence compared with 15 of 180 patients (8.3%) with a mixed or sulphomucin predominant pattern (p less than 0.01). Increased sialomucin staining at the resection margins was associated with reduced survival in these patients (p less than 0.01). At a mean of 14 months of follow up 153 patients (85%) were alive in the sulphomucin group and 53 patients (76%) were alive in the sialomucin group. Regression analysis predicted five year survivals of 32.8% and 18.9% for the sulphomucin and sialomucin groups respectively. Abnormal mucus production at the resection margin in patients treated for colorectal carcinoma appears to identify those with a higher risk of local recurrence and reduced survival.

Aged↗

Impaired spermatogenesis in testes at risk of torsion.

The oligospermia observed after unilateral torsion of the spermatic cord could reflect immunological damage to the opposite testis. An alternative explanation, that there may be a pre-existing defect in spermatogenesis, was tested in 20 post-pubertal males with acute torsion. In a prospective study the contralateral testis was biopsied at operation and the histological appearances were related to subsequent testicular function as assessed by seminal analysis 3 months later. Thirteen patients had biopsy evidence of partial maturation arrest in spermatogenesis which was either mild (6), moderate (4) or severe (3), and ten of these were oligospermic (less than 20 X 10(6)/ml). By contrast all seven patients with normal histology had a sperm concentration greater than 25 X 10(6)/ml. Histological grading of spermatogenesis by the Johnsen technique gave a higher score in patients with a normal biopsy (median 9.01, semi-quartile range 8.96-9.21) than in those with abnormal histology (median 8.28, semi-quartile range 7.98-8.45, P less than 0.001) and correlated with the log of the sperm concentration 3 months later (r = 0.79, P less than 0.001). There was minimal anti-sperm and no anti-testis antibody formation following torsion. Serum FSH levels were raised in 6 of 10 oligospermic patients, while all those with a normal sperm count had FSH concentrations within the normal range. Thus many patients who develop testicular torsion have an underlying defect in spermatogenesis, which correlates closely with poor postoperative exocrine function.

Adult↗

Increased dietary calcium and small bowel resection have opposite effects on colonic cell turnover.

Oral supplements of calcium reduce the mitogenic effects of fatty acids and bile acids on large bowel mucosa. The cytokinetic effects of intraluminal calcium were tested in normal and adapting colonic epithelium. Male Sprague-Dawley rats (n = 60) weighting 356.7 +/- 24.9 g were submitted to either an 80 per cent jejuno-ileal resection or simple transection and resuture of the jejunum. Within each group, half the animals had 24 g/l calcium lactate added to the drinking water. Seven weeks postoperatively crypt cell production rate (CCPR) was determined in the lower descending colon. Among controls with transection CCPR was 4.49 cells crypt-1 h-1; calcium supplements reduced this figure by 26 per cent (P less than 0.05). As expected jejuno-ileal resection increased CCPR (by 51-61 per cent), but again calcium reduced this response by 31 per cent (P less than 0.02). Increased dietary levels of calcium thus inhibit colonic cell turnover and blunt the adaptive response to massive enterectomy, conceivably by binding tropic factors such as bile acids.

Animals↗

The detection of colorectal carcinomas with the use of CA-50 radioimmunoassay inhibition test.

A radioimmunoassay was used for the detection of the human carcinoma-associated antigen CA-50 in the serum of 50 normal subjects, 16 patients with inflammatory bowel diseases and 77 patients with primary and secondary colorectal carcinomas. Serum levels in all normal patients and those with benign disease were below 17 U/ml, while 40 of 77 (51%) patients with carcinoma had levels above 17 U/ml. The sensitivity of this test was 22% for Dukes' A carcinoma, 29% for Dukes' B, 59% for Dukes' C and 73% for metastatic disease. The CA-50 levels were elevated in 7 of 9 (78%) patients who developed tumour recurrence following curative surgery compared with 15 of 43 (35%) patients who are alive and tumour free (p less than 0.05). Therefore, this test may prove useful in the diagnosis and prognosis of patients with colorectal carcinomas.

Adult↗

Pseudo-pseudocysts of the pancreas.

Pancreatic pseudocyst was erroneously diagnosed in three patients aged 52-57 years. Two patients had acute epigastric pain, hyperamylasemia (approximately 4,000 IU/L), and a retrogastric collection of fluid demonstrated by early ultrasonography. Laparotomy undertaken within 48 h of admission revealed the correct diagnosis in each case. One patient had perforation of a gastric ulcer into the lesser sac, and the other patient (who died) had perforation of an obstructed afferent loop 25 years after Polya partial gastrectomy. The third patient with renal failure, back pain, and marginal hyperamylasemia had a cystic mass in the lesser sac. Two internal drainage operations were performed before the correct diagnosis of epithelioid leiomyoma was established 6 years later.

Diagnosis, Differential↗

The tropic effect of intrarectal deoxycholate on rat colorectum is unaffected by oral metronidazole.

Intrarectal administration of sodium deoxycholate (SDC) enhances experimental colorectal carcinogenesis, an effect that is partly vitiated by oral metronidazole. The effect of topical SDC with or without concurrent metronidazole on colorectal cell proliferation was explored in male Sprague-Dawley rats (n = 30) allocated to five groups. Two groups received thrice weekly intrarectal instillations of 1 ml N saline or 1 ml 0.12 M SDC. A third group received SDC plus metronidazole 22.5 mg/kg/day in the drinking water. Controls had no instillations or metronidazole alone. At time of killing (10 weeks), crypt cell production rate (CCPR) was determined by the stathmokinetic technique for four large-bowel segments. Saline had no significant effect on colorectal CCPR but SDC produced increases throughout, varying from 53% in the proximal colon to 222% in the rectum (P less than 0.01). Metronidazole did not reduce this effect, although given alone it reduced colonic CCPR by 40 to 50%. The direct tropic effect of bile acids could largely explain their cocarcinogenic properties. Since metronidazole does not prevent this increase in cell proliferation, its mildly protective role against cancer may reflect the presence of fewer anaerobes capable of degrading bile acids to carcinogenic metabolites.

Administration, Rectal↗

The fate of the human testes following unilateral torsion of the spermatic cord.

In an attempt to explain the oligozoospermia commonly observed after unilateral testicular torsion, 56 patients with acute torsion were investigated prospectively. Blood was taken pre-operatively for antibody studies and a contralateral testicular biopsy was performed at the time of orchiopexy. At review 3 to 6 months post-operatively, late testicular atrophy was assessed and repeat antibody studies were performed together with a hormone profile and seminal analysis. Although the duration of torsion showed a close correlation with the degree of testicular atrophy (P less than 0.001), no such association could be demonstrated between duration of torsion and subsequent sperm concentration. Twenty of 35 patients had histological evidence of a pre-existing partial maturation arrest in spermatogenesis. Fifteen of 19 with the abnormality were oligozoospermic, while all of those with normal testicular histology had a sperm concentration within the normal range. Anti-sperm antibody formation following torsion was minimal and antitestis antibodies were absent. Testes prone to torsion already show impaired spermatogenesis.

Adolescent↗

Proliferative and metastatic potential of exfoliated colorectal cancer cells.

Exfoliated colorectal carcinoma cells were obtained by lavage of 27 freshly resected tumor-bearing segments of human bowel with the use of either Hartmann's solution or medium 199. The tumor cells were isolated from the lavage fluid on Nycodenz (Nyegaard, Oslo, Norway) columns. Their proliferative and metastatic potentials were investigated by their ability to incorporate tritiated thymidine ([3H]dThd) and by their ability to form experimental pulmonary tumors following iv injection into immune-deprived stain A mice. Tumor cells from 7 of 12 patients incorporated [3H]dThd as detected by autoradiography of the cells. Pulmonary nodules of colorectal carcinoma were seen in a single mouse after iv injection of tumor cells from 6 of 17 patients and were histologically distinct from spontaneous lung cancers seen in 3 other animals. No tumors were seen in 12 immune-deprived mice receiving tissue culture medium 199 only. Thus exfoliated colorectal carcinoma cells can undergo further division and might give rise to implantation metastases in humans.

Animals↗

Sugar, fat, and the risk of colorectal cancer.

The habitual diet of 50 patients with large bowel cancer, as assessed by a dietary history method, was compared with that of 50 closely matched controls. Patients were included only if their symptoms were unlikely to have changed previous eating habits. The mean daily intakes of all major nutrient classes and of dietary fibre were estimated. Patients with large bowel cancer consumed 16% more energy than controls (mean (SEM) daily intake 9.92 (0.41) v 8.56 (0.32) MJ (2370 (98) v 2046 (76) kcal), respectively; p less than 0.0001), mainly in the form of carbohydrate (21% more; 282.6 (13.7) v 233.4 (10.5) g; p less than 0.0001) and fat (14% more; 100.8 (4.3) v 88.4 (3.2) g; p less than 0.001). The extra carbohydrate was largely in the form of sugars depleted in fibre and the extra fat as combinations of fat and such sugars. As the selection criteria used make it unlikely that this eating pattern was caused by the disease the data suggest that a high intake of sugars depleted in fibre and fat predisposes to the development of large bowel cancer.

Adult↗