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Biomedical subjects

J G Evans

Publications and source records attributed to J G Evans.

At least 19 recordsLinked to original sources

Comparison of the effects of nafenopin on hepatic peroxisome proliferation and replicative DNA synthesis in the rat and Syrian hamster.

Male Sprague-Dawley rats were fed control or 0.1% nafenopin diet and male Syrian hamsters were fed control or 0.25% nafenopin diet for periods of 7 and 54 days. Nafenopin treatment produced a sustained increase in liver weight and induction of hepatic peroxisomal and microsomal fatty acid-oxidizing enzyme activities, with a greater effect being observed in the rat. Replicative DNA synthesis was studied by implanting osmotic pumps containing [3H]thymidine during study days 0-7 and 47-54. Cell replication, determined either as the hepatocyte labelling index or by incorporation of radioactivity into liver whole homogenate DNA, was increased in rats given nafenopin for 7 and 54 days. In contrast to the rat, no significant effect on replicative DNA synthesis was observed in the Syrian hamster. These results provide further evidence for species differences in hepatic peroxisome proliferation, with the Syrian hamster being less responsive than the rat. Furthermore, while peroxisome proliferators produce hyperplasia in rat and mouse liver, these data suggest that they may not have any marked effect on hepatic replicative DNA synthesis in the Syrian hamster.

Animals

Search for Ha-ras codon 61 mutations in liver tumours caused by hexachlorobenzene and Aroclor 1254 in C57BL/10ScSn mice with iron overload.

C57BL/10ScSn mice administered iron--dextran and fed the environmental pollutants hexachlorobenzene (HCB) and polychlorinated biphenyls (PCBs) develop hepatic nodules and carcinomas within 18 months. A range of lesions from the livers were analysed for the presence of mutations in the Ha-ras proto-oncogene at codon 61 using the polymerase chain reaction to amplify DNA from formalin-fixed sections, followed by oligonucleotide hybridization. Only two mutations from 23 preneoplastic and neoplastic lesions induced by HCB were detected (a focus of altered cells and a trabecular cell carcinoma). With Aroclor 1254 no mutations were detected in 28 areas at various stages of carcinogenesis analysed. Sequencing of the two mutations generated by HCB showed a C-->T transversion at the first base of codon 61 (carcinoma) and an A-->T transversion at the second base (proliferative focus). Thus, in marked contrast to some other systems of mouse liver tumour induction, hepatocarcinogenesis caused by HCB and PCBs in C57BL/10ScSn mice is an example of carcinogenesis which does not involve a high frequency of Ha-ras gene mutation at codon 61.

Animals

The histology and development of hepatic nodules and carcinoma in C3H/He and C57BL/6 mice following chronic phenobarbitone administration.

Male C3H/He and C57BL/6 mice were given diets containing sodium phenobarbitone (PB) to allow a daily intake of 85 mg/kg. Control and treated animals were killed at 5, 30, 40, 60, and 80 wk. Other mice were killed in extremis or at the end of the respective experiments: 91 wk for C3H/He and 100 wk for the C57BL/6 animals. A basophilic nodule was found in 1/5 control C3H/He mice at 30 wk; these nodules increased in number with time so that nodules of this type were found in approximately 70% of animals by 91 wk. Nodules were not found in control C57BL/6 mice until 80 wk, when they were found in 4% of mice. PB treatment markedly increased the number of hepatic nodules in both strains of mice. The additional nodule burden was due to the development of a second nodule type formed of large cells with a predominantly eosinophilic cytoplasm. C3H/He animals given PB for 60 wk and then returned to a control diet bore fewer nodules at 91 wk than treated mice killed at 60 or 91 wk. The cumulative incidence of carcinoma in control C3H/He and C57BL/6 mice was 28 and 4%, respectively. The incidence of carcinoma was not increased by PB treatment in either strain. It is concluded that both strains of mice behave in a qualitively similar way to PB administration, although they show considerable quantitative differences in terms of the time and number of nodules that develop. Furthermore, the increased nodule numbers associated with PB treatment were not accompanied by an increase in the number of carcinomas.

Animals

Who will care for our elderly people?

A conference on the topic 'Who will care for our elderly people?' was held at the Royal College of Physicians on 16 March 1992. It began with a consideration of the challenge in terms of numbers and problems.

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Time spent in hospital by the elderly in the final year of life as a health care indicator: inter-district comparisons.

We have studied the amount of time spent in hospital by elderly people in their final year of life in 1976, 1981 and 1986 in six districts covered by the Oxford record linkage study to determine the extent of differences between districts. There was consistent but insubstantial variation between the districts. Variation declined over time, suggesting that the use of hospital care for the elderly may, in this respect, be nearing consensus. We conclude that the measure of total time spent in hospital by the elderly in their last year of life was not a powerful discriminator between districts in this region. When record linkage is implemented elsewhere in England, it will be possible to make wider geographical comparisons to determine whether important variations exist elsewhere.

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Geriatric primary care: a European perspective, Part I.

Europe is considered the parent of geriatric medicine, which was first recognized as a specialty in the United Kingdom. For the benefit of U.S. primary care physicians, GERIATRICS Editor-in Chief Robert N. Butler, MD, convened a panel of leading European geriatricians in Lausanne, Switzerland, for a discussion of the successes and problems they are encountering in providing medical care to the aging world population. In this first installment, the panelists describe the healthcare services available to the elderly, particularly in the United Kingdom and Switzerland. A physician who is a regional adviser for the World Health Organization adds the perspective of other European nations.

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Geriatric primary care: a European perspective, Part II.

Europe is considered the parent of geriatric medicine, which was first recognized as a specialty in the United Kingdom. For the benefit of U.S. primary care physicians, GERIATRICS Editor-in-Chief Robert N. Butler, MD, convened a panel of leading European geriatricians in Lausanne, Switzerland, for a discussion of the successes and problems they are encountering in providing medical care to the aging world population. In Part I (Geriatrics 1992; 47 [Jan]:31-41) panelists described the healthcare services available to the elderly. In Part II, they discuss treatment and evaluation of dementia, use of hypnotics, rehabilitation approaches, and dietary and exercise recommendations for the elderly.

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Fractures of the hip and distal forearm in West Africa and the United Kingdom.

Comparison of age- and sex-specific incidence rates of fractures of the proximal femur and the distal forearm showed significantly lower rates in Ibadan than in two urban centres in England, with risk ratio of up to 20. In the Ibadan data no evidence of higher rates in women or of a prominent age-associated increase in rates was observed.

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Analysis of the Ha-ras oncogene in C3H/He mouse liver tumours derived spontaneously or induced with diethylnitrosamine or phenobarbitone.

In a study of the mechanisms involved in the induction of tumours by chemicals, the Ha-ras oncogene was analysed in liver tumours induced by the genotoxic carcinogen diethylnitrosamine (DEN), or the non-genotoxic agent phenobarbitone (PB) in C3H/He mice. Mutations were detected using the polymerase chain reaction and oligonucleotide hybridization. Codon 61 mutations were detected in 41% of DEN-induced tumours (19/46), either in the first base (CG----AT, 12/19), a transversion, or the second base (AT----GC, 7/19), a transition. Codon 61 mutations were also found in 29% of spontaneous tumours (all CG----AT, 6/21) but none were detected in PB-induced tumours (0/15) or in normal liver tissue of untreated mice (0/30). No mutations were detected at codon 12. Low and variable expression of the Ha-ras gene was detected in all liver tissues with moderately raised levels (175-200%) in spontaneous, DEN and PB-induced tumours as compared to normal liver tissue. The H-ras gene was methylated to some extent in all liver tissues, with no discernible difference between the treatments. The frequency of the Ha-ras mutation at codon 61 in DEN-induced tumours is greater than in spontaneously arising tumours. This increase is not accompanied by any specific alteration in the expression or methylation of the gene. Since PB-induced tumours do not possess mutations in the Ha-ras gene at codons 12 or 61, the data suggest that the non-genotoxic agent PB induces tumours in the C3H/He mouse liver with a mechanism distinct from that of spontaneous tumours or those that result from treatment with a potent genotoxic carcinogen such as DEN.

Animals

An ultrastructural study of spontaneous and phenobarbitone-induced nodules in the mouse liver.

Male C3H/He mice were given 0 (control) or 85 mg/kg/day phenobarbitone (PB) in the diet. At 40, 60 and 93 weeks, groups of mice were killed and the ultrastructure of spontaneous and PB-induced liver nodules was examined. Treated mice showed typical centrilobular hypertrophy and eosinophilic nodules which may be considered as an end stage lesion. The nodule cells were similar in appearance to those in areas of centrilobular hypertrophy except for the presence of convoluted membranes which are considered to be indicative of proliferation. The incidence of carcinoma was not increased by PB treatment. The carcinomas from control and treated animals differed in their ultrastructure in that increased levels of smooth endoplasmic reticulum (SER) were seen in the carcinomas of the PB animals. The presence of SER proliferation in the carcinomas of PB animals suggests that carcinoma may respond to the enzyme-inducing effects of PB.

Animals

Fractured proximal femur in Newcastle upon Tyne.

Using Hospital Activity Analysis (HAA) data as a diagnostic index followed by record linkage procedures, a retrospective survey was carried out of patients aged 65 and over from the Newcastle area admitted to hospital with fractures of the proximal femur. Annual incidence rates for the Newcastle area of 5.6 per 1000 in females and 2.3 per 1000 in males were observed. These rates are probably 7% lower than true rates owing to patients with multiple fractures being allocated to diagnostic codes other than fractured proximal femur in HAA files. Incidence rates increased steeply with age, and rates in the sexes tended to converge at higher ages. Proportionately large numbers of patients were admitted in the winter months. The mean length of hospital stay was 75.2 days of which an average of 47.8 were spent in acute orthopaedic units: this was equivalent to the continuous occupation of 51.1% of acute orthopaedic beds in Newcastle. At one hospital, mean length of stay was 64% greater than at the other and the weekly discharge rates were suggestive of partly prescriptive discharge. Of the patients studied 35.6% died in hospital, and actuarial analysis shows that risk of death fell from initially high values to a nadir at four to six weeks and then showed a secondary rise.

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A prospective study of fractured proximal femur: factors predisposing to survival.

In a prospective study of patients with fractures of the proximal femur from a defined population it was found that age, mental test score, type of residence, place of injury and hospital of admission were all significantly associated with the likelihood of survival to six months. When these factors were taken into account no additional association between outcome and recorded associated disease, grade of surgeon operating, cigarette smoking, type of operation or social class was demonstrable. These findings have implications for the design of controlled trials of different types of treatment for fractures of the proximal femur.

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