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Biomedical subjects

P W Dykes

Publications and source records attributed to P W Dykes.

At least 19 recordsLinked to original sources
PubMed1993

Haemoccult does not reduce the need for colonoscopy in surveillance after curative resection for colorectal cancer.

Patients who had undergone curative resection for colorectal cancer were studied to compare the efficacy of faecal occult blood detection (Haemoccult test) with colonoscopy in the detection of metachronous tumours. Fifty nine patients were studied and both Haemoccult testing and colonoscopy were successfully completed in 54 patients. In 37 patients, both tests were negative. One patient with a positive Haemoccult test had no colonoscopic abnormality and remains alive and well two years later. There were, however, 16 patients with negative Haemoccult tests in whom an abnormality was found on colonoscopy. In four patients, one Dukes's A cancer and seven tubulovillous adenomas were found--all neoplastic lesions that would have been missed if surveillance had been by Haemoccult alone.

Aged↗
PubMed1991

Comparison of minimal and conventional surgery in patients with bleeding peptic ulcer: a multicentre trial.

A multicentre randomized prospective trial compared minimal surgery (under-running the vessel or ulcer excision and adjuvant ranitidine) with conventional ulcer surgery (vagotomy and pyloroplasty or partial gastrectomy) for the treatment of bleeding peptic ulcer. This report is based on 137 patients (eight withdrawn through misdiagnosis or lost data), of whom 62 received conservative surgery and 67 conventional operation. Twenty-nine patients died, 16 (26 per cent) after conservative surgery and 13 (19 per cent) after conventional operations. The only significant difference between the groups was the incidence of fatal rebleeding, which occurred in six patients after conservative surgery compared with none after conventional surgery (P less than 0.02, Fisher's exact test).

Adolescent↗
PubMed1990

Acute haemorrhage from gastric malignancy.

The presentation, pathology and treatment of 30 patients with acute bleeding from gastric malignancies has been reviewed. Patients usually have a history of symptoms of less than 6 months prior to bleeding. Adenocarcinoma was the commonest type of tumour, and 74 per cent were stage IV lesions. The proportion of lesions in the body of the stomach (57 per cent) was greater than expected, suggesting that these are different populations of gastric tumour. Laparotomy was undertaken in 20 patients, 12 of whom had a resection. Resection was associated with a median survival of 17.0 months. Those with unresectable tumours or who were treated only by supportive measures had a median survival of only 2.5 months (P less than 0.01). Evidence of peritoneal or liver involvement should contraindicate surgical intervention as these patients have a high postoperative mortality rate.

Acute Disease↗
PubMed1990

Theoretical considerations for improving tumour targeting.

To determine the relative importance of factors influencing tumour uptake of antibodies, we used a mathematical model to simulate intravenous injection of substances of varying molecular sizes and tumour-binding affinities at several dose levels. The FACSIMILE program was used to simulate the time course of tumour uptake of the tumour-binding substance by calculating the instantaneous tumour content (TC) and tumour:background uptake ratios (UR). Relative total doses to tumour and normal tissue were calculated by integration of TC/time curves. The model was used to make theoretical predictions on the effects of altering different parameters. The size of the injected dose in relation to the number of tumour receptors was crucial:if too low, uptake could not be improved by manipulating other variables, and if too high, the UR for large binding molecules was reduced. Using the standard scanning dose of labelled antibody, absolute numbers of labelled molecules binding to tumour could be increased by injection of a large excess of unlabelled molecules. Given an adequate dose, peak tumour content increased with increasing affinity up to receptor saturation. The peak uptake ratio rose progressively with affinity for a small ligand, but reached a relatively low plateau for antibody due to constant high background levels. At low doses such as those currently administered for diagnostic scanning with antibody, no effect of increasing affinity was predicted.

Antibodies, Monoclonal↗
PubMed1989

Effect of dose, molecular size, affinity, and protein binding on tumor uptake of antibody or ligand: a biomathematical model.

A mathematical model has been developed to determine the best approach to improving tumor targeting with antibody. The amount of antibody in the tumor (tumor content) and the tumor:normal tissue antibody concentration ratio (uptake ratio) were calculated over 12 days from injection, using the computer program FACSIMILE to solve the stiff nonlinear differential equations describing the system. Results indicate that success requires an optimal combination of dose, size, and binding affinity of antibody. Increasing the dose to 100 times that presently used for scanning increased both the percentage of injected antibody in the tumor and the uptake ratio by up to 2 orders of magnitude to maximal values determined by affinity. This result could be achieved by coinjecting unlabeled antibody. Increasing affinity from Keq = 10(9) to 10(13)M-1 increased the uptake ratio from 5 to 100 for whole antibody and to 550 for a small ligand, at the calculated optimal dose, but had no effect at the current scanning dose. With decreasing molecular size at average affinity, the same maximum tumor content and uptake ratio were achieved but progressively earlier. At high affinity there was a substantial advantage for a small ligand compared with whole antibody in terms of uptake ratio (550 versus 100) and tumor:normal tissue integral dose ratio (330 versus 60). The uptake of a small ligand was not increased by binding to plasma protein but with increasing time the tumor content was higher than without protein binding.

Animals↗
PubMed1989

The effect of routine endoscopy on the detection rate of T1 gastric cancer (early gastric cancer) in Birmingham.

The introduction of routine endoscopy facilities at the General Hospital, Birmingham has made no significant impact on the proportion of stage T1 or 'early' gastric cancers detected. Prior to this, T1 cancers comprised 2.8% of all tumors diagnosed, or 4.2% of resected cases. Following establishment of the service in 1974, 3.2% of all cases and 6.3% of those resected were stage T1 lesions. The clinical presentation reflected the high proportion of tumors associated with ulceration (67%). The accuracy rate for pre-operative diagnosis of a malignant lesion was barium meal 67%, cytology alone 73%, biopsy alone 80%, and cytology and biopsy in combination, repeated if suspicious, 100%. The crude survival rate at 5 years was 83.3% (age-adjusted 96%), and at 10 years 53.8%).

Adenocarcinoma↗
PubMed1989

Enterovesical fistulas in Crohn's disease.

A total of 19 enterovesical fistulas were recorded in a series of 799 patients with Crohn's disease (2.4%). The origin of the fistulas was: ileum (9), colon (6) and four were complex involving the small and large bowel. Only 13 patients presented with urinary symptoms: pneumaturia (9), haematuria (1) and urinary tract infection (3). Four fistulas were identified incidentally during contrast radiology, one fistula was identified during a laparotomy and one further fistula developed after a previous resection for Crohn's disease. Four patients were managed conservatively and all are asymptomatic, but it is not known whether the fistula has healed. Twelve fistulas were resected: 9 healed, 2 recurred and 1 patient died following resection for a malignant fistula complicating Crohn's disease. Early in the series three patients were managed by bypass or defunction of the fistula. In all cases the sepsis persisted resulting in mortality. Persistent symptomatic fistulas should be treated by resection of the affected segment of bowel with primary anastomosis if appropriate. The defect in the bladder should be closed over an indwelling catheter which should not be removed until there is radiological confirmation that the bladder defect has healed satisfactorily.

Adolescent↗
PubMed1987

Selection of patients for surgery following peptic ulcer haemorrhage.

Surgery remains the only widely available and well-proven means of stopping haemorrhage from peptic ulcers and preventing its recurrence but carries an unavoidable morbidity. If surgery is to be used to maximum effect with minimum morbidity, an accurate means of predicting which patients will suffer further haemorrhage is needed. Although over 80 per cent of patients who rebleed have the endoscopic stigmata of haemorrhage, a policy of operation in all patients with stigmata would lead to a very high operation rate and a high proportion of unnecessary operations, as one-half of the patients with stigmata do not rebleed. Clinical data were collected prospectively from 278 cases of peptic ulcer haemorrhage. The data from a randomly selected 75 per cent of the cases were analysed by stepwise logistical regression. Patients who had the endoscopic stigmata of haemorrhage and who had a probability of further haemorrhage, calculated from the regression equation, of more than 0.2 were identified as a high risk group. This definition was validated using the 25 per cent of cases not used in the initial analysis. Eighty-four per cent of patients in the high risk group suffered further haemorrhage and all such patients therefore require early surgery: such a policy would have resulted in an operation rate of 28 per cent. Thirty per cent of the patients who had further haemorrhage were not identified as being at high risk but none of them had a severe rebleed. The regression equation greatly enhanced the value of stigmata in guiding surgical decision making and merits further evaluation.

Aged↗
PubMed1987

Per-endoscopic bipolar diathermy coagulation of visible vessels using a 3.2 mm probe--a randomised clinical trial.

Forty-four patients who had bled from peptic ulcers and whose ulcers showed stigmata of haemorrhage (bleeding, visible vessel or adherent clot) entered a trial of treatment with a 3.2 mm bipolar diathermy probe. Two patients had spurting haemorrhage when endoscoped and both were treated with the probe, control being obtained in one. The remaining patients were randomised to treatment or control groups. One patient who was treated was withdrawn because the ulcer proved to be malignant. Six of 20 treated patients rebled compared with 8 of 21 controls (relative risk 0.79; 90% CI 0.26-1.97). The operation rate, transfusion requirement and hospital stay were similar in the two groups. One perforation occurred in the treatment group. Per-endoscopic bipolar diathermy treatment confers little benefit in bleeding peptic ulcer disease.

Aged↗
PubMed1987

An evaluation of anti-insulin radioimmunodetection in patients with suspected insulinoma.

Nine patients with suspected insulinoma were scanned with iodine-131 labelled anti-insulin. The clinical diagnosis was subsequently confirmed at laparotomy in eight patients, two of whom had liver metastases. The primary insulinoma was accurately localized by anti-insulin scanning in four patients and these tumours ranged from 1 to 3 cm in diameter. Both computerized axial tomography (CT) scanning and pancreatic angiography had given false negative results in one of these patients. Hepatic metastases were correctly identified in one of two patients. No hepatic false positive reports occurred. Positive scan areas were graded as definite, probable or possible. All four of the pancreatic positive results graded as definite or probable positive were correct. Three false positive results occurred in the region of the pancreatic body, all had been graded as possible. Anti-insulin scanning failed to detect four subsequently proven insulinomata (3 mm-2 cm in diameter). Pelvic uptake of anti-insulin occurred in a patient who was found to have a para-ovarian tumour. An homogenate of this tumour also reacted with anti-insulin in a radioimmunoassay. A true negative pancreatic scan was obtained in this patient. We conclude that this technique is insufficiently accurate for routine clinical use.

Adenoma, Islet Cell↗
PubMed1987

Intestinal absorption at high altitude.

Three tests of small intestinal function were performed at 3100 m and 4846 m to seek evidence of malabsorption of high altitude. Xylose tolerance did not change in 11 subjects but, in three who ascended to 5600 m, one-hour xylose levels were significantly lower. The results of an oxalate loading test did not suggest significant fat malabsorption. A direct fat absorption test using chylomicron levels after ingestion of 100 g fat showed significantly increased levels at high altitude. We conclude that there is no evidence of malabsorption up to 4846 m.

Acetazolamide↗
PubMed1987

Limitations to the killing of tumours using radiolabelled antibodies.

We have calculated the minimum requirements for effective therapy using intravenously administered, tumour-directed antibodies labelled with either iodine 131 or yttrium 90. A lethally large amount of either radionuclide would be required to achieve tumour destruction. At least a 10-fold increase in tumour uptake is necessary to combine tumour destruction with a survivable whole-body dose. The required improvement in specific uptake can be substantially reduced by accelerating the excretion of radioactivity outside the tumour. For all situations studied, yttrium 90 is superior to iodine 131 as a cytotoxic label.

Antibodies, Monoclonal↗