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Biomedical subjects

D R Appleton

Publications and source records attributed to D R Appleton.

At least 73 records · Page 4Linked to original sources

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↗

Aspects of statistics in studies of cell proliferation. I. Multistage sampling.

In cell kinetic experiments, as in many other branches of biological science, we often sample at various stages of an experiment: we may for example take a sample of animals, then from each study a sample of sites, and from each site take replicate observations. This sampling process can be optimized to give maximum precision to an estimated quantity, but care must be taken in analysing data so gathered because the analysis depends on the precise sampling strategy.

1,2-Dimethylhydrazine↗

The distribution of the number of maxima in a cyclic sequence.

A simple statistical method is presented which tests for non-randomness in a cyclic sequence. The distribution of the statistic is tabulated for short sequences, and a large sample approximation is derived. Significant values of the statistic are given for sequences of length up to 52. Easily used computer programs to carry out appropriate calculations are presented.

Biometry↗

Are there diurnal fluctuations in crypt length and crypt cell birth rate in the intestines of normal and carcinogen-treated rats?

At eight time points over a period of 24 hours, crypt length (in cells) and crypt cell birth rate were measured by the stathmokinetic method with vincristine and evaluated at two sites in the small intestine and two in the colon in Wistar Porton rats. Normal animals were compared with animals which had received 24 injections, at weekly intervals, of the intestinal carcinogen 1,2-dimethylhydrazine. In the treated animals, crypts were significantly longer at sites prone to tumour formation but not at those sites known to be resistant to the effects of the carcinogen. In neither group of animals was there any significant fluctuation in mean crypt length over a 24 hours period. Crypt cell birth rates showed a considerable fluctuation. No difference was noted between normal animals and those treated with dimethylhydrazine and statistical analysis failed to confirm the presence of any true periodic fluctuation.

1,2-Dimethylhydrazine↗

Use of a dietary diary and interview to estimate the food intake of children.

A recently completed large-scale longitudinal dietary survey is described. The diary and interview method was used within the normal school organisation and proved to be a very acceptable and efficient means of collecting dietary data. Very few problems were encountered with the technique and a relatively low volunteer rate was compensated for by a very low dropout rate. Useful quantitative dietary data is thought to have been obtained and this will be reported at a later date. The data required were primarily concerned with frequency of eating and macronutrient intake; the diary and interview method may be less acceptable for other uses and with other age groups.

Child↗

Human colorectal tumours in short-term organ culture. A stathmokinetic study.

Short-term organ culture, using a technique to preserve epithelial/stromal interaction and metabolism, is a useful technique for carrying out kinetic studies on human colorectal carcinoma and adjacent normal mucosa, providing initial perturbations of proliferative indices are allowed to settle. Tumours require 3.0 micrograms/ml vincristine for complete metaphase arrest compared with mucosa, which needs 0.5 microgram/ml, a 6-fold difference. Using a stathmokinetic technique, the birth rate of tumour cells is 10.21 cells/1000 cells per hr, compared with 7.73 cells/1000 cells per hr for mucosa, a statistically significant difference (P less than 0.01).

Adenocarcinoma↗

Adaptive cell-proliferative changes in the small-intestinal mucosa in coeliac disease.

Cell proliferation in the small-intestinal crypts of rodents has been intensively investigated and lends itself to the deployment of techniques which are inapplicable in man. In particular there are ethical and economic objections to methods involving the use of tritiated thymidine in vivo for specific labelling of DNA, while the validity of in vitro studies using organ culture is uncertain. It is possible, nevertheless to construct a profile of the size and cytokinetic status of the mucosal crypts by analysis of serial sections prepared from well orientated routine diagnostic biopsy specimens. Such studies can provide a measure of mean total crypt-cell population, and by studying the distribution of mitoses in the crypts relative measurements can be obtained of proliferation and maturation compartment sizes, and of crypt cell production rate (CCPR). These parameters have been compared in 62 patients with 'flat' avillous coeliac mucosae and in 85 patients with normal villous mucosae. A heterogeneous group of 47 patients with lesser degrees of abnormality (convoluted mucosae) were similarly studied. In addition, estimates of cell cycle times were obtained in a small group of patients with normal, convoluted and 'flat' mucosae by taking biopsies before and after the administration of the metaphase-arresting agent vincristine. 'Flat' coeliac mucosae show a threefold increase in the size of the proliferation compartment compared with normal and the cell cycle time is approximately halved leading to a net sixfold increase in CCPR. This is the basis of the change in mucosal morphology and presumably represents a compensatory reaction to the gluten-induced increase in loss of enterocytes from the mucosal surface. Convoluted mucosae occupy an intermediate position in terms of the parameters studied and should be regarded as stages in a continuum of adaptive change.

Adaptation, Physiological↗

Crypt regeneration in adult human colonic mucosa during prolonged organ culture.

Using a system designed to preserve, in vitro, both the epithelial and the connective tissue elements, we have maintained adult colonic mucosa in organ culture for up to 336 hours and have investigated the sequential morphological changes which occur. During the first 48 hours, normal micro-architecture is preserved, but there is progressive loss of cytoplasmic mucin from crypt cells. Subsequently, accelerated degenerative changes develop; cells are lost from the crypts and, because cell proliferation in the crypt is reduced, these lost cells are not replaced. For a time, the crypts are represented by discrete acinar formations or clusters of cells in the lamina propria, apparently discontinuous with the intact surface epithelial layer. These remnants manifest intense proliferative activity during the period between 72 and 96 hours after explantation, leading to the restoration of well formed crypts lined by columnar epithelial cells between 120 and 144 hours; differentiation of goblet cells ensues and this state of virtually normal structure persists until the termination of culture between 186 and 336 hours. It is concluded that the determination of normal crypt structure and of crypt-cell differentiation is governed by intrinsic control mechanisms although these may be subject to extrinsic modulation. Whether or not the degeneration phase can be eliminated, it is clear that long term culture of adult human colonic mucosa is possible. Such a system may be useful in the study of mucosal function and of mucosal response to drugs, carcinogens and trophic factors.

Cell Differentiation↗

Acute changes occurring in the intestinal mucosae of rats given a single injection of 1,2 dimethylhydrazine.

In the long term, administration of dimethylhydrazine (DMH) to rats results in the development of tumours in both small intestine and colon. This study has been undertaken in order to document the sequence of changes occurring in the intestinal mucosa in the first 108 h following a single subcutaneous injection of DMH. After a lag of several hours there is evidence of damage to cells in the proliferation zone of the intestinal crypts, and a brief reduction in tritiated thymidine labelling index. A phase of compensatory regenerative activity emerges from the setting of continuing cell damage, resulting in restoration of the mucosa to normal. The severity of the toxic damage to the intestinal mucosa at various sites mirrors the vulnerability of the mucosa to the long term carcinogenic effects of DMH, suggesting that inherent properties of the mucosa may be of more importance than other cocarcinogenic influences in the ultimate development of tumours.

Animals↗

Kinetics of the non-neoplastic mucosa of the large bowel of dimethylhydrazine-treated rats.

Administration of 1,2 dimethylhydrazine (DMH) to rats by weekly s.c. injections causes the development of multiple epithelial tumours of the large bowel. These appear to arise as localized dysplastic abnormalities in hitherto apparently morphologically normal crypts. This study was undertaken in order to examine cell proliferation in such apparently normal crypts of DMH-treated animals. A number of proliferative abnormalities are evident, including changes in the size of the crypts, changes in the disposition of proliferating cells within them and reduced cell-cycle times. The nature and the extent of the abnormalities vary from site to site along the length of the bowel, and reflect the vulnerability of the different segments of the bowel, not only to the carcinogenic effects of DMH, but also to short-term toxicity.

1,2-Dimethylhydrazine↗

Breast-feeding and respiratory syncytial virus infection.

The pattern of breast-feeding in 127 infants admitted to hospital with respiratory syncytial virus infection was compared with that in 503 age-matched controls. Thirty per cent of children with infection had been breast-fed compared with 49% of controls. The approximate relative risk of being admitted to hospital with respiratory syncytial virus infection if not breast-fed was 2.2. Several other factors were also considered, including an assessment of maternal care and home environment; the mother's age, marital state, and smoking habits; the number of siblings; and gestation. Adverse factors were all associated with an increased risk of admission with infection, but breast-feeding still appeared to provide protection after controlling for these other factors in turn. These findings provide further support for encouraging mothers to breast-feed their infants and should prompt further studies into the immune status of mothers and into the nature of the protective factors in their breast milk.

Breast Feeding↗