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Biomedical subjects

D R Appleton

Publications and source records attributed to D R Appleton.

At least 55 records · Page 3Linked to original sources

Dietary sources of energy, protein, fat and fibre in 375 English adolescents.

The aim of this report of the dietary sources of energy, protein, fat and fibre in 375 English adolescents aged 11-14 years is to contribute to the development of health education. Each child recorded their dietary intake five times over a 2-year period using a 3-day diary with interview. Food tables (Paul & Southgate, 1978) were used to calculate nutrient intake. The results are the mean of all 15 days intake. Potatoes (chips and crisps) were the largest single source of energy but 'meat' was the main source of protein and fat, other important sources of fat were the spreading fats, milk, chips and crisps. Chips were the main source of fibre but white bread, crisps and baked beans also contributed similar proportions of fibre. Some differences between the sexes and social classes were observed; the lower social class children appeared to have more undesirable eating habits.

Adolescent

A comparison of crypt-cell proliferation in rat colonic mucosa in vivo and in vitro.

The successful development of a long-term organ culture system has made it possible to perform experiments on rat colonic mucosa in vitro. However, the effect of trauma or the withdrawal of trophic influences in culture may result in the disturbance of proliferation within the tissue. In this paper we describe an investigation designed to characterise the culture system by a comparison of the proliferative parameters in vitro with those in vivo. Stathmokinetic experiments were performed in vivo and in vitro to estimate cell birth rate. Mitotic indices were also calculated. The in vivo birth rate (7.8 +/- 0.8 cells/1000 cells/hour) and the in vitro birth rate for the whole explant (7.7 +/- 0.5 cells/1000 cells/hour) were found to be similar. A study of crypts in the centre and at the edge of the cultured explants, however, indicated that proliferation at the two sites differed markedly, the birth rate at the edge (7.5 +/- 0.9 cells/1000 cells/hour) being approximately twice that at the centre (3.2 +/- 0.9 cells/1000 cells/hour). Provided that this topological difference in proliferation within the explant is recognised the in vitro model, in particular the basal level found at the centre, may still be regarded as a valid system for studying tissue responses to carcinogens and trophic factors.

Animals

The dietary intake of added and natural sugars in 405 English adolescents.

A number of reports have urged a reduction in sugars intake. Implementing this advice depends upon knowledge of sugars intake by target groups. This paper reports the added and natural sugars intake by one target group--young adolescents. The diet of 405 children was recorded using a 3-day diary with interview repeated five times between September 1979 and July 1981. Food tables (Paul & Southgate, 1978) were used and the values for the sugars content of the food items altered to provide both added sugars and natural sugars concentration. The mean daily intake of added and natural sugars respectively, for the 193 boys was 85 g (s.d. 22), 39 g (s.d. 12), and for the 212 girls was 78 g (s.d. 24), 35 g (s.d. 12). Added sugars contributed, on average, 69 per cent of total sugars and 15 per cent of energy intake. Confectionery, table sugar and soft drinks together contained 71 per cent of the added sugars intake, while milk, fruit and their products provided the majority of the natural sugars. It is considered that major reductions of sugars intake would be possible in these children by restricting the intake of a small number of groups of foods of low nutrient density. Food labelling of sugars content would enable consumers to make sensible choices of foods.

Adolescent

Transplantation of a segment of ileum to the external abdominal wall: an animal model of intestinal mucosal hyperplasia.

When a segment of small intestine is transplanted to the external abdominal wall in rats adaptive changes occur in the exposed mucosa. These probably represent an extreme example of a physiological response to one type of trophic influence--the effect of mechanical trauma. The nature of the changes has been studied at 7 weeks after externalization using simple morphometry and a number of cytokinetic techniques (thymidine labelling, vincristine-induced metaphase arrest and the fraction-of-labelled-mitoses method), and comparisons drawn with the normal ileum. The exteriorized mucosa showed marked villus atrophy and hyperplasia of the crypts to three times normal size as a result of increases both in crypt length and crypt circumference. Neither metaplastic nor dysplastic epithelial abnormalities were observed. Crypt-cell production rate doubled in the hyperplastic crypts due to an increase in the size of the proliferation zone within the crypt, and the distribution of proliferating cells within the crypt changed. But cell cycle times were prolonged and more maturing cells were retained in the hyperplastic crypts. The potential usefulness of this model, particularly in carcinogenicity studies is considered.

Abdominal Muscles

Demonstration of vincristine resistance in primary intestinal neoplasms in the rat by the 'post-metaphase index'.

A method is described enabling the direct measurement of vincristine resistance in intact tissues in vivo by morphological study. Using the metaphase arresting properties of the drug, counts were made of escaping anaphase and telophase mitotic figures at a range of doses. The proportion of post-metaphase mitotic figures is called the post-metaphase index (PMI). In 95 primary intestinal tumours induced by dimethylhydrazine (DMH) in rats, an increase in resistance to vincristine was shown over normal mucosa (P less than 0.001). The data were analysed by computer modelling and a linear relationship is demonstrated between the logit of the post-metaphase index, and log dose of vincristine. To achieve a PMI of 1% the fitted lines show an enhanced vincristine dose requirement over normal mucosa of 6 times in colonic tumours, and 8 times in small intestinal tumours. Non-neoplastic mucosa from the DMH-treated animals requires an enhanced dose of vincristine of 1.5 times, compared with normal mucosa, to achieve a PMI of 1%. Given current interest in the mechanism of vincristine resistance in cell lines this new approach provides a technique for assessing the resistance of solid tumours, both in vivo and in vitro, and for subsequent experimental manipulation.

Animals

Aspects of statistics in studies of cell proliferation. IV. Simulation.

Computer simulation of an experiment can help to reveal how effective that experiment might be in estimating cell kinetic parameters, or in elucidating the nature of a proliferative response to a perturbation of the steady state, such as a carcinogenic or therapeutic treatment. Writing a simulation also clarifies one's thoughts about possible mechanisms of the proliferative response.

Cell Division

Vindesine as a stathmokinetic agent in human rectal tumours in organ culture.

Organ culture, using human colorectal mucosa and tumours, is a good system in which to test a new stathmokinetic agent such as vindesine. Using this system we have found that vindesine has similar metaphase-arresting properties to vincristine, including at least a 6-fold dose response difference in its ability to arrest mitosis in mucosa and tumour, mucosa being the more sensitive. Vindesine is a satisfactory stathmokinetic agent, but in view of its greater cost offers no particular advantages over vincristine.

Carcinoma

Presence of epidermal growth factor receptor as an indicator of poor prognosis in patients with breast cancer.

Epidermal growth factor receptors are present in some breast cancers in man, and there is an inverse relation to oestrogen receptor state. We assessed the presence of epidermal growth factor receptors as a single prognostic indicator in a series of breast tumours by comparing this with the Bloom and Richardson scores for these tumours. One hundred and eight ductal tumours were examined for epidermal growth factor receptors by radioligand binding. There was a significant (p less than 0.01) correlation between the presence of the growth factor receptor and poor prognosis as assessed by the Bloom and Richardson score, suggesting that epidermal growth factor receptor state could be a useful prognostic marker. Epidermal growth factor receptor state was not significantly correlated with the lymph node state but showed a tendency to be associated with large tumours.

Breast Neoplasms

Some influences on the measurement of food intake during a dietary survey of adolescents.

Data are presented from a recent longitudinal study of dietary habits of English children aged 11-13 y, in relation to various factors which may have influenced the estimations of intake. A knowledge of such relationships may aid the design and interpretation of this and other dietary surveys. The factors studied included survey fatigue, learning effect, season of the year, day of the week and the subjects' knowledge of the study's purpose. Generally the relationships found were of minor importance, but the variable influence of some of these factors is apparent from a study of the relevant literature. This is one reason why dietary survey methodology is resistant to simplification. It is concluded that the dietary survey method used was adequate for the purpose of the study.

Adolescent

Cell proliferation in human colorectal mucosa in organ culture: the early adaptive changes.

In organ culture tissues undergo adaptive changes which complicate the assessment of proliferative indices. In the present study, a technique devised to preserve collagen metabolism and mesenchymal stroma in tissues of mixed origin was employed to investigate the kinetic behaviour of human colorectal mucosa over the first 24 hours in culture. During this period the structural preservation of tissue is good. The mitotic index in mucosa is profoundly depressed throughout the explants during the first 2-6 hours in culture. During this same period, however, heavy uptake of tritiated thymidine, indicating DNA synthesis, is observed within 150 micron of the cut edge of the samples but not centrally. This phenomenon has been described previously and assumed to be the result of inadequate diffusion of oxygen into the tissue. The 'edge labelling' phenomenon is followed by a wave of mitosis in the tissue edge at 8-18 hours in culture. This delay between tritiated thymidine uptake and the appearance of mitoses in the tissue edge may simply represent the duration of the S + G2 phase of the cell cycle, but is more likely to be due to cells in G1 moving into the S phase followed by cells hitherto blocked in G2 being stimulated into the M phase. After 18 hours the mitotic and labelling indices become more uniform throughout the samples suggesting that 'edge labelling' is partly due to local stimulation of cell proliferation by trauma rather than central inhibition due to diffusion problems. These results suggest that in this organ culture system, assessment of proliferative indices should be carried out after these adaptive changes have settled.

Adaptation, Physiological

Relationship between dietary habits and caries increment assessed over two years in 405 English adolescent school children.

The study was conducted in seven schools on children initially aged 11.5 years. They recorded their diet on five occasions, each of three days, and received an annual dental examination, including radiography. Caries increments were low, mostly (58 per cent) in fissure surfaces. Correlations between caries increment and dietary factors were low due to the low caries increments observed and the large error associated with dietary data where analyses attempt to discriminate between individuals. The highest correlation was between caries increment and weight of daily intake of sugars (+0.143, p less than 0.01). Multivariate analyses revealed that this relationship could not be explained by differences in sex, social class, tooth-brushing habits or level of plaque as measured by gingival inflammation. Weight of sugar intake appeared to be more strongly correlated to caries than frequency of intake; concentration of sugars in foods was positively related, and sugars in snacks were more strongly related to caries than total dietary sugars. The 31 children who consumed most sugar (greater than 163 g/day) developed 5.0 DMFS during the 2 years, 0.9 DMFS per year more than the 31 children (3.2 DMFS during 2 years) who had the lowest sugar intake (less than 78 g/day).

Adolescent

Morphological studies on the long-term organ culture of colonic mucosa from normal and dimethylhydrazine treated rats.

Mucosal explants were prepared from the colons of normal rats and from the non-neoplastic colonic mucosa of rats which had been treated chronically with the intestinal carcinogen dimethylhydrazine. They were maintained in an organ culture system which permitted survival up to at least 25 days. Morphological preservation of the mucosa was excellent up to 6 days in culture and thereafter changes began to occur. But even at 25 days normal crypt structures were still evident. The hyperplastic and dysplastic changes seen in pre-culture samples of DMH-treated mucosae remained recognisable during the first two days in culture. They were no longer seen in explants examined after this time however and, indeed, there appeared to be no difference in the morphology and survival of control and DMH-treated mucosae. It is possible that our culture system does not permit further neoplastic progression, but an alternative explanation is that the system discriminates specifically against the survival of neoplastic elements.

1,2-Dimethylhydrazine

A 2-year longitudinal nutritional survey of 405 Northumberland children initially aged 11.5 years.

Children (405), initially of average age 11.5 years, recorded all food and drinks consumed for three consecutive days (with an interview on the fourth day) on five separate occasions over a 2-year period. Food tables (Paul & Southgate, 1978) enabled nutrient intakes to be calculated. The data collected were found to be of high reliability (Hackett et al. 1983). The mean energy intakes showed broad agreement with other recent British dietary surveys but were well below those recorded in the prewar study by Widdowson (1947) and the FAO/WHO (1973) recommended levels. They were slightly below the current Department of Health and Social Security (DHSS; 1979) recommended intakes. Over the 2-year period, the energy intake of the boys increased by 13% compared with an increase of only 7% in the girls. The iron and vitamin A intakes of all groups of children were low compared with current recommendations (DHSS, 1979). This seems to be a result of falling energy intake. Mean calcium intakes were also only marginally in excess of the recommended intake, and those of most of the girls would fall below the recommendation if the proposal to end the fortification of flour (DHSS, 1981) is implemented.

Ascorbic Acid

The importance of fortification of flour with calcium and the sources of Ca in the diet of 375 English adolescents.

The contribution of the fortification of flour with calcium carbonate to the Ca intake of 375, 11-14-year-old Northumbrian children has been calculated. Mean Ca intakes were above those currently recommended for children of this age. The fortification of flour supplied 16% of the total Ca intakes. Without the fortification, the percentage of these children with intakes below the recommended intake would be more than double. This would include the majority of girls (particularly those of social classes III, IV and V). The recommendation to stop fortifying flour with calcium carbonate should be reviewed.

Adolescent

Sugars-eating habits of 405 11- to 14-year-old English children.

Between September 1979 and July 1981, 405 northern-English children, initially aged 11-12 years, each recorded all food and drink consumed on five occasions on each of three consecutive days. Sugars and nutrient intakes were calculated using food tables. The average total sugars intake was 118 g/d or 21% of the energy intake and 43% of the carbohydrate intake; these percentages were similar for both sexes, all social class groups and surveys. Sugars were found to be derived from a variety of food sources with confectionery being the single largest source. Sugars were fairly evenly consumed over the average day with a high amount in foods eaten between meals. Snacks accounted for 65% of the sugars intake but only 46% of the energy intake. Sugars intake and snacking therefore seem to have been major components of the eating habits of these children. If dietary changes towards lower sugars intakes are to be achieved a vigorous, informed health education campaign is necessary together with effective labelling of manufactured foods, the development of new products and the modification of some existing ones.

Adolescent

Morphometric and kinetic studies on the changes induced in the intestinal mucosa of rats by intraperitoneal administration of quinacrine.

The intraperitoneal administration of large doses of quinacrine in rats results in a state of enteromegaly affecting mainly the distal small bowel, caecum and proximal colon. This enteromegaly is associated with mucosal crypt hyperplasia, and hypertrophy and hyperplasia of the Muscularis propria. In order to investigate the changes in the intestinal mucosal crypts, morphometry and a metaphase-arrest experiment with vincristine were undertaken on a group of rats given 12 mg of quinacrine hydrochloride by intraperitoneal injection daily for 5 days 2 weeks previously, and comparisons drawn with a group of control animals. In the quinacrine-treated animals there was marked enteromegaly affecting the distal small bowel, caecum and proximal colon, and in these segments there was clear crypt hyperplasia. Proximal and distal to the dilated bowel hyperplasia was not seen. No consistent pattern of change in crypt-cell birth rate was evident. The mechanisms by which quinacrine may effect kinetic and morphometric changes in the intestinal crypts are considered.

Animals