Rationing and the health authority.
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Biomedical subjects
Publications and source records attributed to S Griffiths.
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The ability of glucosinolates, the main bioactive components of brassica vegetables, to influence beta-naphthoflavone-induced transcription of human cytochrome P450 1A1 was examined. Human Hep G2 cells, which contain a functional Ah receptor, were transiently transfected with a reporter construct containing the entire promoter sequence of the human CYP1A1 gene. Breakdown products of four of the glucosinolates tested (prop-2-enyl, 3-methylsulphinylpropyl, 2-hydroxybut-3-enyl and p-hydroxybenzyl), at a concentration as low as 1 microM, reduced the level of beta-naphthoflavone-induced transcription of CYP1A1. It is already known that certain glucosinolate breakdown products can induce phase II enzymes and inhibit the catalytic activity of some cytochrome P450 isoenzymes. This study demonstrates that certain alkyl and aromatic glucosinolates may also influence cytochrome P450 1A1 transcription.
AIMS: To study the mechanism of action of steroids in patients with peritumorous oedema. METHODS: To investigate early cerebral metabolic changes proton magnetic resonance spectroscopy (1H-MRS) was used before and 11 to 14 hours after treatment with dexamethasone (12 mg oral loading and 4 mg four times daily maintenance). Nine patients (two men, seven women, mean age 54) with pronounced oedema associated with various intracranial tumours (two astrocytomas, three meningiomas, two glioblastoma, and two metastases) were examined using MRI and MRS. SE1500/135 volume selected MRS (mean volume 21 ml) were performed on an oedematous region and a contralateral region. All spectra were acquired with and without water suppression. Metabolite peak area ratios were determined. RESULTS: Regions of oedema had significantly (P < 0.01) higher unsuppressed water than the contralateral regions, as expected. There was no change at this early time point after dexamethasone. The ratio of the area of choline containing compounds to that creatine and phosphocreatine compounds was determined after which the serial ratios of these before and after were calculated (a serial ratio of 1.0 would indicate no change in the choline to creatine ratios after steroid administration). The mean serial ratios for the area of oedema were 1.02 (SEM 0.08) and 1.10 (0.08) for the contralateral volume of interest, indicating no significant changes. However, significant changes (P < 0.02) were found in the N-acetyl-aspartate (NAA)/choline serial ratios (0.86 (0.06) in the area of oedema, 1.20 (0.10) in contralateral brain) and the NAA/creatine serial ratios (0.86 (0.08) for the oedema, 1.25 (0.11) in contralateral brain). CONCLUSIONS: Such rapid changes may be explained either by relatively large alterations in the relaxation characteristics of NAA or, more controversially, by actual changes in the amounts of NAA. It is proposed that steroids act primarily by causing early metabolic changes that are later expressed in improvements in intracranial volume relations.
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A peptide sequence of a metalloprotease purified from bovine brain [Chantry, Gregson and Glynn (1989) J. Biol. Chem. 264, 21603-21607] was used to design an oligonucleotide probe for screening a bovine brain cDNA library. A contig of the two overlapping cDNA clones that were isolated encoded a 748-amino-acid polypeptide with similarity to the disintegrin-metalloprotease precursor proteins of haemorrhagic snake venom. The bovine protein has been named MADM, for mammalian disintegrin-metalloprotease. The predicted mature protein has 534 amino acids arrayed as extracellular metallo-protease and disintegrin (potential integrin-binding) domains, a transmembrane helix and a basic/proline-rich cytoplasmic C-terminus. Highly conserved homologues of bovine MADM were found in cDNA libraries of rat brain and a human U937 histiocytic lymphoma cell line. A wide variety of mammalian cell lines expressed low levels of MADM mRNA (4.5 and 3.2 kb transcripts) and mature polypeptide (M(r) 62000), as assessed by Northern analysis and Western blotting with an antiserum raised to a peptide within the disintegrin domain. MADM appears to be a rather distantly related member of the reprolysin protein family, which includes both the snake venom disintegrin-metalloproteases and a number of predicted cell-surface disintegrin-containing mammalian proteins.
Simulator port films of 22 set-ups of a complex cranial field positioned by radiographers working either at normal or at increased pace were compared with a control film. Analysis showed that accuracy decreased for set-ups achieved at an increased speed, demonstrating risks to treatment outcomes incurred by increasing working speed to meet workload demands.
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This prospective descriptive study of primary health care workload in the five days after day surgery is based on a questionnaire to patients who received day surgery in a specialist unit in Oxford. Half of all patients received health care, the mean consultation time was 16 minutes, and half the consultations were within two days of surgery.
OBJECTIVE: To assess whether the way in which the results of a randomised controlled trial and a systematic review are presented influences health policy decisions. DESIGN: A postal questionnaire to all members of a health authority within one regional health authority. SETTING: Anglia and Oxford regional health authorities. SUBJECTS: 182 executive and non-executive members of 13 health authorities, family health services authorities, or health commissions. MAIN OUTCOME MEASURES: The average score from all health authority members in terms of their willingness to fund a mammography programme or cardiac rehabilitation programme according to four different ways of presenting the same results of research evidence--namely, as a relative risk reduction, absolute risk reduction, proportion of event free patients, or as the number of patients needed to be treated to prevent an adverse event. RESULTS: The willingness to fund either programme was significantly influenced by the way in which data were presented. Results of both programmes when expressed as relative risk reductions produced significantly higher scores when compared with other methods (P < 0.05). The difference was more extreme for mammography, for which the outcome condition is rarer. CONCLUSIONS: The method of reporting trial results has a considerable influence on the health policy decisions made by health authority members.
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Two patients with atypical manifestations of aberrant peroxisomal biogenesis are described. Contrary to previous studies, which had shown that Zellweger syndrome patients usually have normal levels of urinary oxalate excretion, the patients in the present study had evidence of abnormal oxalate metabolism in the form of hyperoxaluria and, in one of the patients, calcium oxalate urolithiasis. Activity of the liver-specific peroxisomal enzyme alanine:-glyoxylate aminotransferase (AGT), which is a major determinant of the level of endogenous oxalate synthesis in humans, was normal in one patient and markedly supranormal in the other. Using the technique of post-embedding protein A-colloidal gold immunoelectron microscopy, AGT was found to be mainly cytosolic in the livers of both patients, with significant amounts also localized in the nuclei. In a small minority of the hepatocytes of one patient, who was homozygous for the more common (major) AGT allele, large numbers of unidentified fibrillar arrays were found in the cytosol, which labelled heavily for immunoreactive AGT. The background cytosolic AGT labelling was markedly reduced in such cells when compared to the majority of cells that did not contain fibrils. In the other patient, who was heterozygous for the major and minor AGT alleles, there appeared to be low levels of mitochondrial AGT labelling. In the light of these data, the possible metabolic function of cytosolic AGT in the livers of panperoxisomal disease patients is discussed.
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