"Deadly experiments". UK's programme was open and ethical.
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Biomedical subjects
Publications and source records attributed to D C Evered.
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A survey was carried out of the undergraduate backgrounds and research achievements of 885 (94.1%) of all 940 medically qualified professors and readers in medical faculties in the United Kingdom. A total of 217 (24.5%) of the graduates in these senior academic positions had graduated from Oxford or Cambridge and 137 (15.5%) had an intercalated BSc. The corresponding figures for a control group matched for sex and date of graduation were 118 (13.3%) for Oxford and Cambridge (academic to control odds ratio 2.11:1) and 34 (3.8%) for the BSc (odds ratio 4.58:1). Those with an intercalated BSc in the clinical specialties raised substantially more research grants from the Medical Research Council than their peers from Oxford and Cambridge or those without a BSc. The Oxford and Cambridge group raised more grants in the non-clinical specialties. Bibliometric analysis was carried out on the United Kingdom graduates within the broad specialty of medicine (n = 218) matched for date of graduation. Academics with a BSc had a better publication record over 10 years (median number of original publications 72) than the Oxford and Cambridge group (median 59) and a substantially better record than those from other schools without a BSc (median 46). Citation analysis was carried out on subsets of the above sample matched for date of graduation and frequency of publication. Those with an intercalated BSc were cited more often (8.04 citations/paper) than the Oxford and Cambridge graduates (7.63) and substantially more than their peers without a BSc (4.16). These data show very clearly that research training or experience, or both, as an undergraduate has a substantial influence on career development and correlates positively with subsequent research performance many years later.
The importance of research evaluation is now well recognised in some quarters but this activity is being looked upon as essentially negative by others. We believe this view to be mistaken. The case for investing some money in research evaluation is essentially a very straightforward one. It is clear that a significant fraction of the money spent on research will be wasted (ie, will produce no usable data--positive or negative--on any time-scale and will be of no educational or training value). The problem is, and has always been, that there is no way of knowing in advance which fraction of the resources will be wasted. That is the nature of research and we would not argue that it could or should be otherwise. Research is about exploration and discovery and it is inevitable that some scientific endeavours will be fruitless. Research evaluation can help to minimise resource wastage and thus the case for conducting research on research is entirely positive. Analytical techniques are available to examine the ways in which we train research workers, fund research workers, and assess research outputs; and these should be applied with a view to improving the system. There is also a strong case for setting up an effective mechanism for strategic forecasting and planning, and an urgent need to take a radical look at the entire range of biomedical research activities in the UK. It is essential that the research community should take steps to evaluate its performance and adopt a positive approach to planning. If it does not do so, assessments will be made by those without a fundamental understanding of the nature of the enterprise, and the prospects for any further increases in public support would appear to be bleak.
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One hundred and sixty-three asymptomatic people with thyroid antibodies or raised serum thyrotrophin (TSH) concentrations, or both, and 209 age-matched and sex-matched controls without either marker of thyroid disorder were followed up for four years to determine the natural history of autoimmune thyroiditis. Mildly raised TSH concentrations alone and the presence of thyroid antibodies alone did not significantly increase the risk of developing overt hypothyroidism during the four years compared with the controls. Overt hypothyroidism developed at the rate of 5% a year in women who initially had both raised TSH concentrations and thyroid antibodies. Prophylactic treatment with thyroxine may be justified in women found to have both markers of impending thyroid failure. The cost effectiveness of screening the adult population remains to be evaluated.
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Eighteen patients with Cushing's disease were seen over a 40-month period and considered for treatment by pituitary irradiation and adrenal blocking drugs. Fourteen patients entered the study and each received megavoltage therapy to give a mean dose of 4600 rad to the pituitary over 31 days. Each patient was treated for one (two patients) or two (12 patients) years with one or both of the adrenocortical enzyme inhibitors, metyrapone or aminoglutethmide to suppress cortisol secretion. Doses were adjusted to maintain urinary free cortisol secretion below 300 nmol/24 h. One patient failed to complete the trial. Normal urinary free cortisol excretion and plasma cortisol concentration were maintained after treatment in eight of the remaining 13 patients after therapy. Only one patient required cortisol replacement and normal menstrual function was restored in five of the six women. The remaining five patients relapsed and four were subsequently treated by total adrenalectomy. It was noted that the patients who responded to treatment were substantially younger than the therapeutic failures. It is suggested that this treatment is most useful in the management of younger patients.
We have studied the effects of 131I therapy on thyrotrophin binding inhibiting immunoglobulins (TBII) in fifty-five patients with Graves' disease and five patients with toxic multinodular goitre (MNG). A group of forty patients with Graves' disease and four patients with toxic MNG were treated with drugs and acted as controls. In 78% of patients treated with 131I there was a marked increase in the serum TBII activity during the 3 months following therapy, whereas drug-treated patient showed a decrease (77%) or no change in TBII activity over the same period. TBII activity was not detectable in patients with toxic MNG before or after drug or 131I therapy. Consideration of the mechanisms involved in the changes in serum TBII activity after 131I treatment or during drug treatment provide insight into the basic defects responsible for the development of hyperthyroid Graves' disease and suggest that both the thyroid and immune system are involved.
Hypothalamo-hypophysial-thyroid function has been studied in twenty-five patients with chronic renal failure. Eight were receiving conservative treatment, nine peritoneal dialysis and eight haemodialysis. All were clinically euthyroid. Total thyroxine (T4) and triiodothyronine (T3) levels were reduced but free T4 levels were normal, while free T3 was reduced in patients with the most severe renal failure. It is suggested that the binding of thyroid hormones by the transport proteins is reduced and that peripheral conversion of T4 to T3 is impaired in renal failure. The thyrotrophin response to thyrotrophin-releasing hormone (TRH) is reduced in renal failure but this reduction is probably independent of alterations in thyroid hormone metabolism. Growth hormone was released by TRH in seven of the patients studied, possibly as a result of protein malnutrition.
Changes in thyroid hormone concentration and distribution and plasma cortisol levels have been followed in 11 patients undergoing elective cholocystectomy. A significant rise in total and free thyroxine (T4) and fall in total and free triiodothyronine (T3) were noted after surgery. Reverse T3 concentrations rose substantially, suggesting that peripheral conversion of T4 to T3 is diminished and that there is preferential formation of reverse T3. Serum thyroid stimulating hormone concentrations did not change. There was no direct correlation between the change in cortisol and the change in thyroid hormone or reverse T3 concentrations.
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Serum total and free thyroid hormone concentrations were estimated in 42 patients with epilepsy taking anticonvulsants (phenytoin, phenobarbitone, and carbamazepine either singly or in combination). There was a significant reduction in total thyroxine (TT4), free thyroxine (FT4), and free triiodothyronine (FT3) in the treated group compared with controls. Free hormone concentrations were lower than total hormone concentrations, suggesting that increased clearance of thyroid hormones occurs in patients receiving anticonvulsants. Detailed analysis indicated that phenytoin had a significant depressant effect on TT4, FT4, FT3, and reverse T3 (rT3). Phenobarbitone and carbamazepine had no significant main effects, but there were significant interactions between phenytoin and carbamazepine for TT4 and FT4. phenobarbitone and carbamazepine for FT3, and phenytoin and phenobarbitone for rT3.
Total thyroid hormone concentrations have been measured in the course of a large scale community survey to determine the distribution of these variables in the normal population and to assess the effect of age, sex, previously undectected thyroid disease and medication upon these parameters. 2779 subjects were studied. Serum T4 concentrations were normally distributed. A progressive increase in T4 levels with age was noted in the males, and a smaller increase in females which was concealed by the raised T4 values secondary to oral contraceptive therapy in females under the age of 45. Serum T3 levels were also normally distributed. There was a small reduction in T3 with age in the males but this fall was not seen in the females. T3 values were relatively higher in females under the age of 45 but this increase was not noted after exclusion of subjects taking an oral contraceptive. The changes in thyroid hormone concentrations with age are relatively minor (particularly with respect to T3) in a randomly selected sample from an English town. It is suggested that the changes reported by other authors reflect the process of selection used, and the high frequency of undetected thyroid disease, other illness and medication in hospital-based communities.
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Thirty consecutive patients with hyperthyroid Graves' disease received a 6-month course of antithyroid drugs. Sixteen patients relapsed within 6 months of the withdrawal of antithyroid therapy. All patients with high levels of thyroid-stimulating antibodies (TSAb) at the time of drug withdrawal relapsed within 2 months of discontinuing the antithyroid treatment while all patients with low or undetectable TSAb activity at the time of drug withdrawal remained in remission. It was not possible to predict the disease course in patients who had intermediate levels of TSAb when antithyroid therapy was stopped.