Measuring mission effectiveness.
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Biomedical subjects
Publications and source records attributed to J Bond.
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The p53 gene has been implicated as a tumour suppressor, with mutations occurring in many carcinomas, such as colon, breast and lung. We have sequenced exons 5, 7 and 8 containing conserved gene regions in the only available differentiated thyroid follicular carcinoma cell line and found a mutation at position 273, Arg----His, with no normal allele present. The same mutation was also present in DNA from the tumour of origin. However immunohistochemical analysis of 129 human thyroid tumours using a panel of p53 antibodies was unequivocally negative. Southern blotting in 20 cases failed to demonstrate any deletion or rearrangement, and direct genomic sequencing of 20 carcinomas showed normal DNA sequence for exons 5, 7 and 8. Thus p53 abnormalities may not be important in human thyroid carcinogenesis, in contrast to colon, breast and lung. However, the FTC 133 cell line was only established after 132 unsuccessful attempts with other differentiated thyroid follicular tumours. Since this line and the corresponding tumour of origin have a p53 mutation, we propose that p53 mutation may confer on thyroid follicular tumour cells the ability to grow in culture. This has potential applications for the future development of thyroid carcinoma cell lines.
1. The effects of hyperthyroidism and hypothyroidism on the concentrations of glutamine and other amino acids in the muscle and plasma and on the rates of glutamine and alanine release from incubated isolated stripped soleus muscle of the rat were investigated. 2. Hyperthyroidism decreased the concentration of glutamine in soleus muscle but was without effect on that in the gastrocnemius muscle or in the plasma. Hyperthyroidism also increased markedly the rate of release of glutamine from the incubated soleus muscle. 3. Hypothyroidism decreased the concentrations of glutamine in the gastrocnemius muscle and plasma but was without effect on that in soleus muscle. Hypothyroidism also decreased markedly the rate of glutamine release from the incubated soleus muscle. 4. Thyroid status was found to have marked effects on the rate of glutamine release by skeletal muscle per se, and may be important in the control of this process in both physiological and pathological conditions.
The effects of physiological and pathological concentrations of glucocorticoids were investigated using the glucocorticoid antagonist RU486 and the synthetic glucocorticoid dexamethasone, respectively. The effects of these treatments on the concentrations of glutamine and other amino acids in skeletal muscle and plasma and on the rates of release of glutamine and alanine from incubated preparations of skeletal muscle of the rat were investigated. Dexamethasone treatment increased the concentration of glutamine and the rate of release of this amino acid from incubated soleus muscle preparations. This treatment decreased the concentration of glutamine in both gastrocnemius and EDL muscles, but was without effect on the rate of glutamine release from EDL muscles. In contrast, administration of the glucocorticoid antagonist RU486 decreased the rate of glutamine release from muscle. It is concluded that glucocorticoids have marked effects on the metabolism of glutamine by skeletal muscle per se and that these hormones may be important in the control of the rate of glutamine release from muscle in both physiological and pathological conditions.
In summary, hyperthyroidism increased the rate of glycolysis and decreased glycogen synthesis in isolated incubated rat soleus muscle preparations. SKF 901 also increased glycolysis, but the stimulation was 5-fold less than in T3-treated muscles. Hyperthyroidism increased the rate of glutamine release from skeletal muscle, but SKF 901 did not affect glutamine metabolism.
OBJECTIVE: To assess the impact of HIV on procedures to control infection in general practices. DESIGN: A postal questionnaire survey. SETTING: General practices throughout Britain. SUBJECTS: 5359 General practitioners, 3429 (63.9%) of whom returned the questionnaire. MAIN OUTCOME MEASURE: Response to questionnaire on knowledge about HIV and policies for controlling infection. RESULTS: Most doctors (2018) had started to wear gloves when taking blood. Almost half (1510) had not resheathed needles previously but a further 776 had adopted this policy because of HIV. Over half of the doctors did not know or were unsure about the risk of infection from needlestick injuries, and 1759 had no practice policy for controlling infection. CONCLUSIONS: Many doctors are uncertain about measures to control infection in general practice. More information and advice are needed to help doctors develop policies to protect patients and staff.
Statistical assessment of papers submitted to the British Medical Journal has increased to some 300 papers annually. The assessment produces a recommendation to the editor on each paper from a statistical viewpoint together with a completed checklist that indicates the quality of certain important features. This exploratory study was aimed at monitoring the process. It reports a comparison of checklist answers on 45 papers as originally submitted with those on the papers as subsequently published. Of the 45 papers, only 5 (11%) were considered statistically acceptable at submission, but this increased to 38 (84%) after publication. Revisions had not been made adequately in 4 of the 7 unsatisfactory published papers, and the 3 others were thought to be of dubious validity. A major omission from at least 28 papers was information on sample size calculations. It is concluded that statistical assessment is beneficial but that further efforts by authors and assessors could make it even more effective.
This paper reports outcome data from a multiple-case study of the three experimental NHS nursing homes and six hospital wards undertaken as part of the evaluation of the experimental NHS nursing homes. While all subjects were very frail, NHS nursing home residents were found to be less frail than those in hospital wards. Significant differences in favour of the NHS nursing homes were found in the proportion of subjects engaged in meaningful activity during the mornings and afternoons, in the amount of activity and contact with others during the hour preceding lunchtime, and in amount of verbal interactions over lunchtime, particularly when choices were offered. These outcome data support the findings of other studies carried out as part of the evaluation that there is no evidence to imply that continuing-care accommodation should not be provided in NHS nursing homes.
A postal survey of 5243 community nursing staff throughout England sought information about their experience, education, knowledge, confidence and beliefs in relation to the human immunodeficiency virus (HIV) and the acquired immune deficiency syndrome (AIDS). A response rate of 74% was obtained. While experience of patients positive for HIV antibody or with AIDS was limited, one-third of community nursing staff had encountered patients worried about HIV infection. However, most lacked confidence to provide health education, counselling and terminal care. A quarter felt that they should have the right to refuse to care for patients with AIDS, while 85% were concerned about their lack of experience. In order to play an effective role in the prevention and management of HIV infection, community nursing staff need to be assisted in making links between knowledge they already possess and its application to HIV infection, and in developing and practising skills.
Enzymatic activity, biosynthesis, and maturation of lactasephlorizin hydrolase (LPH) were investigated in adult volunteers with suspected lactose intolerance. Mean LPH activity in jejunal biopsy homogenates of these individuals was 31% compared to LPH-persistent individuals, and was accompanied by a reduced level of LPH-protein. Mean sucrase activity in individuals with low LPH was increased to 162% and was accompanied by an increase in sucrase-isomaltase (SI)-protein. Biosynthesis of LPH, SI, and aminopeptidase N (APN) was studied in organ culture of small intestinal biopsy specimens. In individuals with LPH restriction, the rate of synthesis of LPH was drastically decreased, reaching just 6% of the LPH-persistent group after 20 h of culture, while the rate of synthesis of SI appeared to be increased. In addition, maturation of pro-LPH to mature LPH occurred at a slower rate in LPH-restricted tissue. Immunoelectron microscopy revealed an accumulation of immunoreactive LPH in the Golgi region of enterocytes from LPH-restricted individuals and reduced labeling of microvillus membranes. Therefore, lactose intolerance in adults is mainly due to a decreased biosynthesis of LPH, either at the transcriptional or translational level. In addition, intracellular transport and maturation is retarded in some of the LPH-restricted individuals, and this leads to an accumulation of newly synthesized LPH in the Golgi and a failure of LPH to reach the microvillus membrane.
We have previously shown that activation of ras oncogenes by mutation is a frequent early event in human thyroid neoplasia. Using amphotropic retroviral vectors to achieve gene transfer, we demonstrate here that human primary thyroid epithelial cells can be partially transformed by an activated cellular or viral Ha-ras oncogene, in the absence of a cooperating oncogene. The transformation event induced by ras involves temporary rescue from senescence for up to 20 rounds of cell division together with morphological alteration, growth factor independence and anchorage independence. It has therefore been possible to reconstruct in vitro a key early event in the genesis of human epithelial neoplasia.
Since colorectal adenomas are very probably the precursors of colorectal cancer, their detection and removal should result in a decrease in the incidence and mortality from colorectal cancer. Individuals who harbour an adenoma have a 30-50% probability of having additional adenomas at that time, and a 30% probability of having additional adenomas later. Adenomas are prevalent in countries where colorectal cancer is prevalent, about two-thirds of them being tubular and the rest tubulovillous or villous. The initial management of patients with an adenoma consists in searching by colonoscopy the entire colon and removing all additional polyps. Surgical resection is required wherever there is invasive cancer with adverse histological factors. Follow-up in most patients can be after 2-4 years, earlier follow-up being reserved for patients with numerous polyps or with a polyp that had been removed piecemeal. The results of ongoing trials should provide firm guidelines for follow-up and could also be used in mathematical modelling to examine alternative strategies and to help understand the evolving patterns of appearance of new polyps. Finally, a deeper understanding of the biology and inherited and acquired genetics will help identify individuals at risk for adenomas initially and at follow-up. Nutritional factors may also provide a basis for prevention of adenomas in high-risk countries. Many of these issues are being addressed in current research.
In mid-1988 a postal survey was conducted of one in five general practitioners in England and Wales, to examine their contact with people with human immunodeficiency virus (HIV) infection, with the acquired immune deficiency syndrome (AIDS) or with worries about HIV infection or AIDS. The response rate was 63.9%. Of the 3339 respondents 22.7% knew of an asymptomatic HIV positive patient within their practice, 5.4% knew of a symptomatic HIV positive patient and 6.4% knew of a patient with AIDS. The estimated annual rate for HIV-related consultations in general practice (including consultations with the 'worried well') was 6.5 per 1000 population. HIV-related consultations occurred more frequently in the four Thames health regions than elsewhere. A sample of 715 practitioners who reported consultations with HIV infected people or those with worries about infection in the previous month, were invited to keep a diary of HIV-related consultations for one week. The response rate to the diary was 64%. Nineteen per cent of the 273 consultations recorded in the diaries were initiated by homosexual men, 16.5% by injecting drug users, 10.3% by the sexual partners of people at risk of infection; 42.9% of consultations were not associated with recognized risk factors. The results indicate that general practitioners have substantial contact with patients with HIV infection, with AIDS and with worries about HIV infection or AIDS. This contact is likely to increase, alongside the anticipated spread of HIV infection, with consequent implications for general practice resources.
Recent developments in screening, diagnosis and treatment of colon cancer could lead to a reduction in mortality from this disease. Removal of adenomas, identification of risk factors, appropriate application of accurate diagnostic tests, and aggressive anatomic-surgical resection of colon cancers may already be having a favourable impact. Screening of average-risk populations over the age of 50 also offers promise in the control of this important cancer. The disease is of sufficient magnitude to deserve detection at an early stage with better prospects of patient survival, since screening tests with moderate sensitivity and high specificity are available. Flexible sigmoidoscopy and faecal occult blood tests are sufficiently acceptable to be included in case-finding among patients who are in the health care system. The results of current controlled trials involving more than 300,000 individuals for evaluating the impact of screening on mortality from colon cancer are needed before this approach can be recommended for general public health screening of the population. Further research is required to develop better screening tests, improve patient and physician compliance, and answer more definitively critical questions on cost-effectiveness. Mathematical modelling using current and new data can be used to determine the effectiveness of screening in conjunction with recommendations for primary prevention.
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1. The effects of non-lethal bacteraemia or endotoxaemia on insulin-stimulated glucose metabolism were studied in isolated, incubated soleus muscle of rats after 24 and 48 h. 2. The insulin-stimulated rates of lactate formation and glycogen synthesis were similar in muscles isolated from control and bacteraemic rats. 3. Endotoxaemia increased the rates of lactate formation, at all levels of insulin, both at 24 h (approximately 32%) and 48 h (approximately 26%). Endotoxaemia did not alter the sensitivity of glycolysis to insulin. 4. Endotoxaemia decreased the rates of glycogen synthesis at all concentrations of insulin both at 24 h (approximately 39%) and 48 h (approximately 23%). 5. The increase in the rate of glycolysis was related in a dose-dependent manner to the amount of endotoxin given to the animals. 6. Endotoxaemia decreased plasma tri-iodothyronine levels (41%). However, the effects of endotoxaemia (48 h) on glucose metabolism in muscle are similar to those caused by hyperthyroidism. In hypothyroid rats, endotoxin administration increased the rates of glycolysis in muscle in vitro. 7. It is concluded that there are enhanced basal and insulin-stimulated rates of glycolysis in soleus muscle from endotoxaemic rats. This may be due to both increased glucose transport and decreased glycogen synthesis.
General Practitioners are excellently placed within the community to provide health education and advice in relation to HIV infection and AIDS. This paper will report on some of the findings from the first national study of HIV infection and general practice in England and Wales. The findings cast light on the preparedness of practitioners to undertake health education on HIV infection. Findings that relate to the extent of contact that practitioners have with people with HIV infection, people with AIDS and people with worries about HIV infection or AIDS will be discussed in the light of opportunities that are created for HIV-related health education and prevention. Findings that relate to practitioners' opinions about providing health education and counselling, about working with people who are gay, bisexual and injecting drugs, and about confidentiality and consent, will be discussed in the light of obstacles that exist to the effective provision of HIV-related health education and prevention. The paper will conclude by discussing the implications of these findings for primary health care responses to HIV infection in Britain.