Bioethics in ethically pluralist societies.
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Biomedical subjects
Publications and source records attributed to M Charlesworth.
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Concentrations of the sum of 15 PAHs in 22 surficial sediment samples from the western Irish Sea ranged from below 100 ng g(-1) in sandy sediments to a maximum of 1422 ng g(-1) in the centre of the mud basin. The concentrations are typical of coastal shelf sediments, but greater than those observed for aquatic sediments remote from known anthropogenic sources. Organic C and the % sediment <15 microm were positively correlated with sigmaPAH. sigmaPAH was normalised to organic C and particle size (i.e. expressed as sigmaPAH/C(org) and sigmaPAH/% < 15 microm) and significant relationships were still observed with organic C and % < 15 microm. The results are discussed in the context of using organic C to normalise concentrations of PAHs to assess contamination levels in sediments.
Polycyclic aromatic hydrocarbons (PAHs) were sampled from 30 sediment and 8 mussel (Mytilus edulis) stations in two Northern Irish Sea-toughs. Analysis was performed by gas chromatography coupled to mass spectrometry (GC-MS). Sedimentary organic carbon, % silt/clay and mean grain size were analysed in order to assess the role of geochemistry on PAH distribution. With the exception of two sites in Larne Lough representing localized regions of high contamination, sum(PAHs) in sediments ranged between 83 and 2300 ng g(-1). Regression analysis indicated that particle size and organic C were dominant factors in controlling the distribution of PAHs throughout the sediments. Sources of PAHs in both sea-loughs were dominated by pyrogenic inputs suggesting that diffuse sources such as atmospheric deposition may be a major source to both water bodies. The sum of PAHs in mussels ranged between 95 and 184 ng g(-1). Variations in concentrations may be explained by differences in the condition between mussel populations. Mussels in both sea-loughs exhibit similar metabolic activities towards the PAH compounds which were predominantly bioaccumulated from sediments.
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Rathke's cleft cysts are cystic sellar and suprasellar lesions, characteristically lined by a single layer of ciliated cuboidal or columnar epithelium. In contrast, craniopharyngiomass, which are also cystic sellar and suprasellar lesions, are characteristically lined by stratified squamous epithelium with keratinization on a layer of connective tissue. The usual management recommended for Rathke's cleft cysts is simple surgical drainage with partial excision of the cyst wall. Recurrences of these cysts reportedly have been very rare. This retrospective study presents the details of 12 patients (6 females; median age 30 yr, range 21-58 yr) with Rathke's cleft cyst, referred to our department over a 15-yr period (1981-1996), an unusual feature being the recurrence of 4 (33%) of these lesions. Clinical, endocrine, radiological, surgical (10 transsphenoidal; 2 transcranial), and pathological details were recorded. Nine out of 12 patients (75%) were symptomatic; visual symptoms were the commonest, and 8 had visual field defects. The median duration of symptoms was 12 months (range 3-24 months). Three patients (25%) had panhypopituitarism, 2 of whom also had diabetes insipidus (17%). The cysts varied in size from 6 mm to 50 mm, 1 being entirely suprasellar. There were no pathognomonic clinical or radiological features to differentiate them from other pituitary lesions, although the presence of diabetes insipidus in 2 patients suggested that the lesion was not a pituitary adenoma. A definite histological diagnosis was possible in 8 patients; in 4, the diagnosis was presumptive. The median duration of follow-up was 30 months (1-168 months). Four patients (33%) showed reexpansion at 3, 6, 48, and 48 months after initial surgery, 3 of whom were symptomatic and required repeat surgery. Two of these patients were given postoperative external beam pituitary radiotherapy. Apparent recurrence of Rathke's cleft cysts after initially successful surgery in our series was higher than suggested by previous reports, and thus, long-term follow-up with pituitary imaging and neuroophthalmological assessment is essential. There are no specific characteristics of the cyst that predict recurrence. Ideal management of these cysts is unclear, but aspiration, followed by extensive excision of the cyst wall when possible, seems to be the best initial option. For recurrent symptomatic tumors, surgical resection is the treatment of choice. Considering the high recurrence rate with residual structural and functional dysfunction, the role of radiotherapy in preventing recurrence of these cysts needs careful evaluation with a larger study with a longer follow-up period.
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OBJECTIVE: Lymphocytic hypophysitis is a rare disorder which usually affects women and is often associated with pregnancy. We reviewed our experience of this disorder in order to see whether these features were universal amongst our patients. DESIGN: A retrospective review of case notes. PATIENTS: Four patients with histologically proven lymphocytic hypophysitis. MEASUREMENTS: Each patient had undergone full radiological and biochemical assessment of anterior and posterior pituitary function. RESULTS: Only one woman presented during pregnancy, one patient was a man with coexistent active acromegaly, and one progressed over 5 years to panhypopituitarism. In one further patient, histological analysis revealed normal anterior pituitary tissue adjacent to lymphocytic follicles. CONCLUSIONS: Lymphocytic hypophysitis should be considered in the differential diagnosis of any patient with a pituitary mass. We suggest that the entire removal of such a mass is warranted both for accurate diagnosis and definitive treatment.
Ten patients were studied prospectively afer severe closed head injury to determine the relationship between long-term clinical outcome and abnormalities detected by single photon emission tomography (99Tcm-HMPAO SPET), CT and MRI obtained within 60 days of injury. The ability of SPET to detect abnormalities not visualized by CT or MRI after cerebral trauma by the results of this study. Changes detected by SPET [global cerebral blood flow (gCBF) and number of regional cerebral blood flow (rCBF) deficits] soon after trauma were shown to be more closely correlated with long-term outcome than changes detected by MRI or CT. Templates were used to classify lesions by site and a multivariate analysis was undertaken to establish the importance of defect position in predicting clinical outcome. The results suggest that lesions in the temporal lobes, frontal lobes and basal ganglia are related to poor prognosis, and that SPET yields more useful prognostic data than the other methods.
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After closed head injury nineteen patients had single photon emission tomography (SPECT) using the lipophilic tracer 99m-Technetium hexamethyl-propylene-amineoxime (HMPAO) to compare the defects shown by CT and MRI. SPECT showed more focal cerebral lesions than either CT or MRI alone or in combination. Most lesions shown by SPECT were not shown by CT or MRI in the corresponding anatomical regions. The most severely disabled patients showed the highest number of SPECT lesions (average four per patient) and the lowest (mean, SE) cerebral blood flow (718, 69 ml/min) compared with the less disabled patients (two per patient and 1058, 51 ml/min, p less than 0.05). There was a correlation between the Glasgow Outcome Scale grade and the global cerebral blood flow (r 0.74, p less than 0.05). The perfusion defects may correlate with clinical signs that were not explained by CT or MRI findings. SPECT may complement the clinical evaluation in the assessment of outcome after head injury.
The possibilities opened up by human genome analysis appear to provide support for quasi-deterministic views of human nature but an analysis of the debate over sociobiology shows that we cannot derive a theory of human nature directly from biological and genetic evidence. From this perspective human genome analysis and the forms of human genetic engineering that it makes possible cannot alter our concept of human nature although they make us more aware of the 'plasticity' of the human. The possibility envisaged by some neo-eugenicists (and often accepted by their opponents) of a radical reshaping of human nature is as misconceived as the view of some sociobiologists that human nature is biologically determined. Human genome analysis raises formidable ethical, social and legal problems and we need to develop criteria that will enable us to decide which kinds of genetic manipulation will help to enhance human life and which will not. This will involve having a clear concept of human nature and the values it implies. But we shall not derive this concept of human nature from genetics itself.
The potential long-term toxicity of central nervous system prophylaxis (CNS-P) in adult acute lymphoblastic leukaemia (ALL, n = 17) and non-Hodgkin's lymphoma (NHL, n = 7) was investigated in a multidisciplinary study. At least 4 years had elapsed from CNS-P (mean 11.5 years) for all patients. Neurological history and physical examination were unremarkable; minor signs were commoner in older patients (P less than 0.02). Psychometry yielded normal results, but individual verbal IQ generally exceeded performance IQ, with a trend to more marked differences in younger adults (P = 0.06). EEG was scored and differed significantly from that of controls, with a tendency to more marked (but still minor) abnormalities in younger patients (P = 0.06). Brainstem auditory evoked potentials demonstrated significant but generally minor abnormality in 24% of patients. CT brain scan revealed widening of cerebral hemisphere sulci to greater than 3 mm in 38% of patients; cerebral atrophy was commoner in the older group (P less than 0.02) and those with neurological signs (P less than 0.02). MRI brain scans were normal in all patients tested. Thus, following standard CNS-P for ALL at this hospital, there is a 5% primary CNS relapse rate, and only minimal, mainly subclinical, long-term neuropsychological toxicity.
Fourteen patients presented with arrested pubertal development associated with prolactin-secreting pituitary tumours; serum prolactin ranged from 4000-104,300 mU/l in the ten females and 920-68,000 in four males. Skull X-ray showed a markedly expanded pituitary fossa in eight patients. CT scan and/or air encephalography showed macroadenomas in nine, of whom seven had large suprasellar extensions to their tumours, yet only five had complained of headache and only two had visual field defects. All were treated with bromocriptine (7.5-60 mg/day) which lowered prolactin substantially in all and into the normal range in 11 (range less than 60-3090, median 105 mU/l). Puberty thereafter progressed spontaneously in 13, but in one patient, whose prolactin did not suppress completely, menarche could be induced only with clomiphene. Anterior pituitary function improved on bromocriptine. In seven patients with macroadenomas, tumour shrinkage into the pituitary fossa was complete and in two others incomplete shrinkage was followed by transsphenoidal hypophysectomy. Seven patients received pituitary irradiation, six after bromocriptine-induced shrinkage and one after transsphenoidal surgery. At follow-up 6 months to 10 years (median 5 years) after presentation, ten remain on bromocriptine with a suppressed serum prolactin, one has a normal prolactin after surgery, and three are off bromocriptine with residual hyperprolactinaemia (418-4680 mU/l). To date, four females have become pregnant and one male has fathered two children. Prolactinomas are an important, albeit rare, cause of arrested puberty and should therefore be sought. Most patients respond well to bromocriptine, with or without pituitary irradiation.
Four cases of periventricular contrast enhancement on computed tomography due to different tumours are reported, emphasizing that periventricular contrast enhancement is a non-specific radiological sign.
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Cognitive function was assessed, and unenhanced CT head scans were carried out in 44 patients with renal failure. Thirteen had been on regular hemodialysis for 5 years or more (long-term hemodialysis group, LTHD), 12 had received hemodialysis for less than 5 years (short-term hemodialysis, STHD), 9 were on continuous ambulatory peritoneal dialysis (CAPD group) and 10 had severe chronic renal failure and were near to-but had not reached-dialysis dependence (chronic renal failure group, CRF). Employing an index of deterioration (the "discrepancy score") based on the discrepancy between current reading skills and current performance on the Wechsler Adult Intelligence Scale, 6 LTHD patients, 2 STHD patients, 2 CAPD patients and 5 CRF patients were identified as functioning below their predicted premorbid optimum level. Cerebral sulci were abnormally wide in 22 patients (8 LTHD, 2 STHD, 6 CAPD and 6 CRF) and one of the STHD group also had cerebral ventricular dilatation. Nine patients had both an abnormal scan and evidence of cognitive deterioration, 13 had an abnormal scan in the absence of such evidence and 6 had evidence of cognitive deterioration and a normal scan. Both cognitive deterioration and the CT scan finding of widening of cerebral sulci were commoner in these patients than would be expected in an age-matched sample of the general population, but no simple relationship was found between anatomical abnormality and cognitive functioning. Statistically significant correlations were found between discrepancy score and the cumulative amount of aluminum prescribed to be taken orally in both LTHD and CAPD groups.
The presence at presentation of hyperprolactinaemia and abnormalities on high resolution computed tomographic (CT) scanning of the pituitary gland have been documented in 19 patients with primary hypothyroidism. The changes on thyroid hormone replacement were followed for up to 28 months after presentation. At presentation serum PRL was elevated in 12 subjects (454 to 2612 mU/l); after stabilization of thyroid replacement PRL remained raised in 9 patients (525 to 1888 mU/l) despite 10-18 months of treatment. Pretreatment CT scans showed enlarged pituitaries in 11 patients with suprasellar extension in five. In 11 patients there was initially an area of low attenuation suggesting a microadenoma and on rescanning this appearance remained in five patients. Hyperprolactinaemia in hypothyroid patients does not always return to normal with thyroid hormone replacement.
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