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Biomedical subjects

G D Thomas

Publications and source records attributed to G D Thomas.

At least 55 records · Page 3Linked to original sources

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↗

Response rates and survival in patients with head and neck cancer treated with a combination of cisplatin and 5-fluorouracil prior to radiotherapy.

Fifty-three previously untreated patients with advanced head and neck cancer were given courses of cisplatin and 5-fluorouracil prior to radical radiotherapy. The overall response rate to chemotherapy alone was 66% but only two cases achieved a complete response. After radiotherapy, 62% were in complete remission but there was no evidence for improved overall survival when compared to historical data. Patients who responded to chemotherapy had a significantly better chance of achieving a complete remission after radiotherapy, and had a significantly improved survival when compared to non responders to chemotherapy, including those whose disease disappeared after radiotherapy. The survival data compare favourably with other series claiming higher complete and partial responses to the same combination of drugs.

Adolescent↗

Quality assessment in cervical cytology: a pilot study.

A pilot study of an external quality assessment scheme was run between February 1985 and September 1986 to (i) assess the feasibility of running one from a district general hospital; (ii) to estimate the time required to organise and run it with a computer; (iii) to provide sound statistical results with which future schemes could be compared. Seven laboratories participated, and the 20 smears selected from each laboratory were circulated in three rounds in batches of seven, seven, and six according to a prearranged order. Results analysed using the kappa statistic showed moderate levels of interlaboratory agreement, with complete agreement emerging only on a small proportion of cases.

Computers↗

Coronary sinus orifice atresia and persistent left superior vena cava. A report of two cases, one associated with atypical coronary artery thrombosis.

Fourteen previously reported cases of atresia of the coronary sinus ostium, in which the coronary venous flow entered the right atrium by a persistent left superior vena cava, the innominate vein, and the right superior vena cava, are reviewed and two new cases reported. The first new case was in a 43 year old woman with atypical chest pains in whom investigations for suspected ischaemic heart disease, including coronary arteriography, yielded normal results. She died suddenly from massive myocardial infarction due to extensive old thrombotic occlusion of a major coronary artery without any appreciable underlying disease of the vessel wall. Exercise testing is considered to be advisable in symptomatic patients with normal coronary angiograms and attention to the venous phase might be informative. The second new case occurred in a child with an atrial septal defect and complete transposition of the great arteries, who died aged 1 month.

Adult↗

Observer variation in the histological grading of rectal carcinoma.

The variation between two observers in grading 100 biopsies and the corresponding main specimens of rectal carcinomas has been examined. Using kappa statistics, which take account of chance agreement, we found a highly significant level of agreement. As expected, higher levels were obtained for intraobserver agreement. However, disagreements between observers were in many instances "haphazard" and there were differences in bias between them. Fifty paired biopsies and main tumours were graded by five observers and the results analysed for bias and by kappa statistics for overall and conditional agreement. These methods revealed significant overall agreement but the levels for some observer pairs did not differ significantly from chance. Examination for observer bias indicated differing standards of grading, and haphazard disagreements reached high levels for some observer pairs. The intraobserver agreement between the grade of the biopsy and the corresponding main tumour varied from 56-69% but only 52% of the poorly differentiated tumours were diagnosed as such in the preoperative biopsy by the "specialist" observer. The poor predictive value was not improved by taking multiple biopsies. We conclude that the grade of a rectal carcinoma cannot be accurately assessed on a preoperative biopsy and that this has serious implications for the management of low rectal cancers. Furthermore the wide discrepancies in diagnostic standards between some pathologists mean that studies on the treatment and prognosis of rectal cancer which utilise histological grade for comparison purposes must be viewed with considerable skepticism.

Biopsy↗

Effect of horn flies on vanilmandelic acid excretion of dairy cattle.

This study measured a physiological effect of known horn fly (Haematoba irritans L.) population densities on dairy cattle. Urinary excretion of the catecholamine metabolite, 3-methoxy-4-hydroxy mandelic acid, was an indicator of physiological response to the parasites. Six lactating Holstein cows were acclimated to the test room prior to a 3-wk control at 21 C. Animals were then exposed to approximately 500 horn flies per cow per day for 4 wk. On days 1 and 21 of exposure, two urine samples were obtained from each cow. Mean urinary values for cows were 13.3 +/- 3.1 mug/100 ml in the control period and 18.9 +/- 3.4 mug/100 ml during fly exposure. We believe that increased vanilmandelic acid reflects an increase in standing time and nervous activity associated with the physical disturbance due to the biting of the flies.

Animals↗