Health care rationing. Implicit rationing is not open to public scrutiny.
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Biomedical subjects
Publications and source records attributed to L H Breimer.
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Doctoral theses represent a largely inaccessible mine of useful information. There is no simple way of finding out whether someone in another institution has written a thesis that is relevant to your own work, or of reading it. Here, we describe how this situation could be remedied by making theses freely available and easy to search in an international 'Thesis-Line' accessible through the Internet.
The possibility that low concentrations of serum bilirubin may be associated with increased risk of ischemic heart disease has been examined in a prospective study of 7685 middle-aged British men. During 11.5 years there were 737 major ischemic heart disease (IHD) events. A U-shaped relationship was observed between serum bilirubin and risk of IHD. Low bilirubin was associated with several cardiovascular risk factors, in particular smoking, low concentrations of high-density lipoprotein cholesterol, low forced expiratory volume in 1 s, and low serum albumin. The U-shaped relationship persisted even after adjusting for several risk factors. Compared with men in the lowest fifth of the distribution (bilirubin < 7 mumol/L), those in the middle range (8-9 mumol/L) showed a 30% reduction in relative risk [RR = 0.68 (95% confidence intervals 0.51-0.89)] in IHD, whereas men in the top fifth (> 12 mumol/L) showed similar risk to the lowest fifth [RR = 0.99 (95% confidence intervals 0.73-1.34)], which persisted after exclusion of men with bilirubin > 17 mumol/L. The significance of this U-shaped relationship is unclear, but it could be interpreted as support for the role of endogenous antioxidants in the etiology of IHD.
Direct DNA sequence determination of PCR amplified exons of the tyrosinase gene of three British patients suffering from tyrosinase negative oculocutaneous albinism has revealed three new missense point mutations: (1) an adenine to guanine transition at codon 1 changes the initiating methionine codon into a valine codon thereby abolishing translation; (2) a thymine to cytosine transition at codon 370 changes a methionine to a threonine residue; (3) a cytosine to thymine transition at codon 367 changes a histidine to a tyrosine residue. A codon 402 change previously considered a polymorphism is assigned a pathological role.
Unequal access to higher medical degrees, which are important for career advancement, is a problem that is likely to plague UK medicine as integration within Europe proceeds. This paper analyses the characteristics of M.D.s at the Royal Free Hospital School of Medicine and proposes a solution of creating a common European doctorate.
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Doctoral theses submitted in medical schools under a system dependent on publications (Sweden) and one which was not (UK) were compared. A subset consisting of UK theses containing papers (about 1/3 of all UK theses) was used. The publication-based theses gave candidates a significantly higher (P < 0.03) profile in terms of key authorship positions. Nevertheless, in 66% of the UK theses with papers the candidate was either the first or sole author. Swedish and UK theses with papers were of equal quality when assessed by the number of papers in journals: a) ranked in the top 100 (14% vs 10%) or 200 (26% vs 32%); or b) used more than once and either ranked in the top 1000 (median 224 vs 218) or in the top two thirds by subject section (98 vs 100%). UK theses benefitted from the greater impact of journals emanating from the UK compared to continental Europe (P < 0.001). An estimated 13% of UK PhD theses overall included three or more papers per thesis despite no requirement of publication. A publication-based doctorate should be introduced on trial in parallel with the existing systems to ensure efficiency and international comparability.
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DNA repair limits the mutagenic, and thereby the carcinogenic, effect of DNA modifications. Free radicals, particularly reactive oxygen species, induce all forms of DNA damage, including base modifications, base free sites, strand breakage, and cross-links. These lesions are repaired by a variety of enzymes of partly overlapping substrate specificity, some of which may be induced.
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The calcitonin/CGRP multigene complex encodes a family of peptides: calcitonin, its C-terminal flanking peptide, katacalcin, and a third novel peptide, calcitonin gene-related peptide (CGRP). The 32-amino acid peptide calcitonin inhibits the osteoclast, thereby conserving skeletal mass during periods of potential calcium lack, such as pregnancy, growth, and lactation. This hormonal role is emphasized by observations that lower circulating calcitonin levels are associated with bone loss and that calcitonin replacement prevents further bone loss. Structurally, CGRP resembles calcitonin and has been implicated in neuromodulation and in the physiological regulation of blood flow. Here we review the molecular genetics, structure, and function of the calcitonin-gene peptides as analyzed in the laboratory and focus on more recent clinical studies relating to disorders and therapeutics.
The effects of epidural analgesia on plasma calcitonin gene-related peptide (CGRP) values during and after hysterectomy were investigated in 14 healthy patients. In seven patients who received general anaesthesia alone for pelvic surgery, there were no significant changes in plasma CGRP concentrations. In the remaining patients, who received extensive epidural blockade in addition to general anaesthesia, there were again no significant changes in plasma CGRP values. This was in spite of profound sympathetic blockade, as shown by marked hypotension and a significant decline in plasma catecholamines. The epidural group of patients showed the expected attenuation of the glucose, cortisol and growth hormone responses to surgery. The results show that circulating CGRP is unlikely to be involved in the modulation of peripheral vascular tone during pelvic surgery under either general or epidural anaesthesia.
Calcitonin (CT) is produced ectopically from a variety of non-thyroidal cancers. The CT genes also encode another peptide, calcitonin gene-related peptide (CGRP) which is a potent vasodilator. In the present study we have used immunochemical and chromatographic methods to demonstrate the presence and characterize the molecular forms of CGRP in cultured human cancer cells. Using two highly sensitive and specific radioimmunoassays, we have detected immunoreactive CGRP (i-CGRP) in cell extracts and cell-exposed media of cultured promyelocytic leukaemia (HL60) and bronchogenic carcinoma (BEN) cells. The mean i-CGRP content of the HL60 and BEN cell extracts was 2 and 45 pmol/g wet weight respectively. On gel filtration and high performance liquid chromatography, the immunoreactive material was found to be heterogeneous, though a major proportion co-eluted with synthetic human CGRP(1-37), suggesting structural identity with the intact CGRP molecule. Finally, we have discussed some interesting features of CT-gene peptide expression in tumour cells.