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Biomedical subjects

D R Appleton

Publications and source records attributed to D R Appleton.

At least 37 records · Page 2Linked to original sources
PubMed1991

Effects of gastrointestinal peptides on azoxymethane-treated colonic mucosa in vitro.

An organ-culture system has been used to investigate the effect of certain gastrointestinal peptides on the morphology and cell proliferation of explants of azoxymethane (AOM)-treated colonic mucosa. Our aim was to ascertain whether such factors play a direct part in the maintenance of hyperplastic changes in the large intestine. Explants of AOM-treated colonic mucosa from 15 animals were maintained in a serum-free medium in the presence of either gastrin-17 (250 pg/ml and 250 ng/ml), peptide YY (80 pmol/l and 160 pmol/l) epidermal growth factor (EGF) (10 ng/ml and 100 ng/ml) or the C-terminal fragment of glucagon-37 (30 pmol/l) for a period of up to 7 days. Other explants (controls) received fresh medium only each day. After 1, 2, 3, 5 and 7 days of culture both experimental and control explants received vincristine (4 micrograms/ml) for 3 h prior to fixation. The proportion of vincristine-arrested metaphases within the explants was determined together with crypt length. Neither gastrin nor peptide YY was found to influence cell division at either concentration. Despite an initial inhibitory effect, both concentrations of EGF exerted a trophic effect which increased with time. The glucagon-37 fragment caused an immediate increase in proliferation which then declined as time progressed. None of these factors, however, were able to maintain the hyperplastic changes seen in the pre-culture samples of AOM-treated mucosae.

Animals↗
PubMed1990

What statistics should we teach medical undergraduates and graduates?

It is suggested that the emphasis on teaching statistics to medical undergraduates has usually been quite wrong: that the courses have become much too long, too detailed, and irrelevant to the needs of the majority. Examples are given which may help to introduce the basic concepts which all medical (and dental) undergraduates require, and which form a basis for the more traditional teaching of analytical methods to the appropriate subset who proceed to undertake medical research.

Curriculum↗
PubMed1990

The use of computer simulation in the design and analysis of cell proliferation experiments.

The simulation language CELLSIM is used to model a population of cells undergoing proliferation, death and migration. It is shown that standard analytical methods can successfully describe the system in its unperturbed state, but may be considerably in error if the system has recently been subjected to cytotoxic insult. It is suggested that laboratory experiments should be performed on perturbed systems only if simulations have shown that the methods of data analysis will be satisfactorily powerful and accurate.

Animals↗
PubMed1990

The effect of sulindac on colonic tumour formation in dimethylhydrazine-treated mice.

Dimethylhydrazine has been used to produce colonic tumours in mice. If sulindac, a non-steroidal anti-inflammatory drug, is administered simultaneously fewer microadenomata and fewer macroscopic tumours are produced. Those which do appear are comparable in size to the ones in the mice which do not receive sulindac. Sulindac therefore appears to exert an anti-tumour influence at the stage between dysplasia and the formation of microadenomata.

Adenoma↗
PubMed1990

Particle release from haemodialysers.

Release of particles from eight makes of hollow-fibre and one make of flatplate dialyser have been studied, and the relationship between rinsing volume and particles recovered established. In a supplementary study the effect on the number of particles released was assessed when striking the dialyser header during priming. Particle size distribution indicated that the majority of the particles recovered were less than 5 microns in diameter. A separate analysis of the particles in the 5-30 micron size range showed two different patterns of particle release. In the dialysers containing ethylene vinyl acetate (EVAL) or Cellulate the number of particles recovered were within the 95% range of the particles in the rinsing fluid and did not alter with increasing rinsing volume. In the dialysers containing Cuprophan and Hemophan the initial particle numbers were higher but fell rapidly up to a 450 ml rinse volume; increasing the rinse volume to 1050 ml did not alter particle recovery. Analysis of variance failed to differentiate between individual dialysers. Striking the header during priming resulted in a transient statistically nonsignificant increase in the number of particles recovered.

Biocompatible Materials↗
PubMed1990

Anti-glomerular basement membrane (GBM) glomerulonephritis in the mouse: development of disease and cell proliferation.

In a mouse model of anti-glomerular basement membrane (GBM) glomerulonephritis, associated with the nephrotic syndrome, a wide range of morphological and proliferative responses was seen in the renal corpuscle, at 6 days. The severity of the damage could be assessed by measuring the average daily weight gain between days 0 and 3 (DWG) of the animal. Those animals with a high DWG showed capsular proliferation, whereas animals with a low DWG showed predominantly tuft cell proliferation. Capsular cell birth rate increased with DWG whilst tuft cell birth rate was negatively related. A computer simulation suggests that the results are compatible with the induction of successive but overlapping waves of tuft and capsular cell proliferation.

Animals↗
PubMed1989

Proliferative status of colonic mucosa in organ culture: 3H-thymidine-labelling studies and computer modelling.

3H-thymidine labelling studies and a computer simulation have been employed to assess proliferative status and cellular organisation in colonic explants maintained in culture for 5 to 7 days. The one-hour flash labelling index (Is) for crypts within the middle region of explants (5.2%) was considerably lower than that observed in vivo (8.8%). Crypt length and the distribution of labelled cells appeared similar for both situations. A computer simulation program for crypt-cell proliferation was devised, facilitating the modulation of a number of parameters including the cell-cycle time (Tc) and its component phases, the cut-off position, and cell loss at mitosis. This simulation was employed to model continuous labelling (72 h) data obtained in vitro and provided an estimate of various kinetic parameters. Data for the middle region of explants was fitted with a Tc of 62 h, an S phase of 8 h and a cell loss factor (20%) which was consistent with histological findings. A fit to the experimental data obtained in vitro could be achieved by a model based upon a mode of cellular organisation known to occur within crypts in vivo. Therefore in vitro, the dynamic processes of crypt-cell proliferation and migration appear to be organised in the same manner as seen in vivo.

Animals↗
PubMed1989

A protocol for the routine measurement of lactate and pyruvate in cord blood.

The influence of the site of sampling and the delay in sample collection on cord blood concentrations of lactate and pyruvate were investigated. A delay in sample collection of greater than 1 min after cord clamping could invalidate the results obtained. Samples from umbilical artery had higher lactate values (mean 3.13 mmol/l) than paired vein samples (mean 2.32 mmol/l) but there were no significant differences in lactate values between different sites sampled within the umbilical vein. A calculation was devised to circumvent the need to take cord blood samples immediately after delivery.

Blood Specimen Collection↗
PubMed1988

A protective effect of sulindac against chemically-induced primary colonic tumours in mice.

Sulindac, a non-steroidal anti-inflammatory drug, has been reported to lead to tumour regression in cases of human polyposis coli. We have investigated the effects of this drug on the growth of 1,2-dimethylhydrazine (DMH)-induced mouse colonic tumours. In one experiment, DMH and oral sulindac were administered concurrently to a group of mice for a period of up to 24 weeks, while a control group of animals received DMH only for the same period. Sulindac caused a significant reduction in both the number of mice with colonic tumours and the number of tumours per mouse. In a second experiment, two groups of mice which had already been treated with DMH for 17 weeks received either sulindac or not for 78 days. In this experiment sulindac had no effect. These results demonstrate that sulindac has a protective effect against the chemical induction of colonic tumours in mice, but does not cause the regression of established tumours.

1,2-Dimethylhydrazine↗
PubMed1988

Verapamil sensitizes normal and neoplastic rodent intestinal tissues to the stathmokinetic effect of vincristine in vivo.

A morphological method has been developed allowing measurement of the effect on intestinal epithelia of vincristine. In routinely prepared tissue sections the proportion of mitotic events progressing beyond metaphase is counted by microscopy. When estimated over a range of doses of vincristine this post-metaphase index (PMI) can be used to compare the sensitivity of differing intact tissues. Intestinal tumours were induced in rats by chemical carcinogenesis. Administration of vincristine in the presence or absence of verapamil was performed in these tumour-bearing animals. Sections were prepared from colonic and small-bowel tumours and from normal mucosa. The results show that verapamil increases the sensitivity of the tissues studied to vincristine. A dose dependent effect of verapamil on vincristine sensitisation was demonstrated in colonic tissues. These findings indicate a shared pharmacological property between the resistance of primary tumour tissue and the multidrug-resistance phenotype.

Animals↗
PubMed1988

Analysis of data in nephrology. V. Contingency tables.

The first article in this series dealt with 2 x 2 contingency tables. We now return to contingency tables and discuss those formed by a dichotomous response variable and a discrete, but not dichotomous, explanatory variable. The logit transform is introduced.

Data Interpretation, Statistical↗
PubMed1988

Analysis of data in nephrology. II. When to use the t-test.

This is the second of a series of six articles describing how to choose the most appropriate statistical method to test for relationships between two variables. When the response variable is continuous and the explanatory variable is dichotomous, the t-test is often used. The article indicates when this is really appropriate and when the test should be modified or replaced by another.

Data Interpretation, Statistical↗
PubMed1988

Analysis of data in nephrology. III. Survival analysis and analysis of variance.

In this article discussion is continued of the case where the response variable is continuous and the explanatory variable is discrete. Two particular situations are covered: the response variable survival time and the explanatory variable dichotomous: and the response variable continuous (but not survival time) and the explanatory variable discrete (but not dichotomous).

Analysis of Variance↗
PubMed1988

Analysis of data in nephrology. VI. The generalised linear model.

This is the last of six articles describing how to choose the appropriate statistical test to look for relationships between two variables. It shows that when the response variable is dichotomous and the explanatory variable is continuous it may not be appropriate to carry out a t-test. Some comments are made on extending the tests considered to more complex situations.

Analysis of Variance↗