BCG vaccination in children born to HIV-positive mothers.
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Biomedical subjects
Publications and source records attributed to A G Davies.
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Certain oestrogens on substitution with halogens, have been shown to retain receptor binding affinity and accumulate in target tissues and therefore could, when labelled with gamma-emitting halogen isotope, act as radiopharmaceuticals for the imaging of receptor positive breast tumours. In order to evaluate putative radiopharmaceuticals, 17 alpha-Z-iodovinyloestradiol ((17 alpha,20Z)-21-iodo-19-norpregna-1,3,5(10),20-tetraene-3,17 beta-diol) and its 3-acetate have been chemically synthesized and labelled with 125I. Tissue distribution studies in female rats have been compared to those obtained using 17 alpha-E-[125I]iodovinyloestradiol ((17 alpha,20E)-21-[125I]iodo-19-norpregna-1,3,5(10),20-tetraene-3,17 beta-diol) and its 3-acetate and to 16 alpha-[125I]iodo oestradiol (1,3,5(10)-estratien-16 alpha-[125I]iodo-3,17 beta-diol). All compounds showed a similar tissue distribution with the highest concentrations (cpm/g tissue) in the thyroid greater than liver greater than uterus greater than kidney greater than lung greater than blood greater than heart, spleen. The concentration in the uterus was highest after injection of 17 alpha-Z-iodovinyloestradiols or 16 alpha-iodo oestradiol. Target (uterus) to background (blood) tissue ratios were highest after injection of 17 alpha-Z-iodovinyloestradiol-3-acetate and 16 alpha-iodo oestradiol (6:1). Deiodination in vivo took place to a small degree, amounting to 1.6%, 0.9% and 0.35% of the injected dose after 4 hr with the 17 alpha-Z, 17 alpha-E and 16 alpha compounds, respectively. For reasons of chemical expediency and consideration of the biological results 17 alpha-Z-iodovinyloestradiol-3-acetate is the compound of choice for the detection of oestrogen receptor positive tissues.
A novel phenomenon of interactions between genotypes of the dieldrin-resistance (Rdl) locus of the Australian sheep blowfly (Lucilia cuprina) is described. Susceptible adult flies exposed to dieldrin-resistant (Rdl/Rdl or Rdl/S) adults, raised from larvae grown on media containing sublethal concentrations of dieldrin, display mortality related to the concentration on which the resistant flies developed. The resistant flies excrete quantities of dieldrin that are toxic to susceptible flies. These observations provide an additional mechanism to those previously identified for the rapid evolution of resistance to dieldrin by L. cuprina.
The changes in the sagittal alignment of the lumbar spine were investigated in 28 patients with adolescent idiopathic scoliosis undergoing long posterior spinal fusion to L4 or L5 with contoured Luque rods and segmental sublaminar wiring. The lumbar lordosis over the instrumented levels was preserved, and there was no compensatory hyperlordosis of vertebral segments distal to the fusion. In situations where long posterior spinal fusions are indicated, instrumentation with contoured Luque rods and segmental sublaminar wiring can preserve the normal sagittal alignment of the lumbosacral spine.
This study formed part of a psychological survey of young people aged 10-17 years attending three Bristol diabetes clinics. The aim was to examine the characteristics of those who were admitted to hospital with unstable diabetes during the period between two assessments, and analyse how they differed from the rest. Ten young people were admitted to hospital during the study period. These 10 individuals had greater emotional difficulty with diabetes as measured by diabetes specific psychometric scales (median scale score: 19) compared to the 89 adolescents who were not readmitted (median scale score: 14) (p = 0.01). They did not differ in demographic characteristics or glycaemic control. Overall there was no relationship between psychological response to diabetes and glycaemic control as assessed by mean glycated haemoglobin. Five of those admitted presented with hyperglycaemia; they had greater emotional difficulty (median scale score: 31, p = 0.02) and a more negative attitude (median scale score: 22, p = 0.02) to diabetes than those presenting with hypoglycaemia (median scale scores: 16). Only those with hyperglycaemia differed from those who were not readmitted, having greater emotional difficulty (p = 0.002) and a more negative attitude (p = 0.01). The possibility of psychological difficulties with diabetes should be sought following an admission, particularly for hyperglycaemia.
Radioiodinated monoclonal antibodies (MCA) were administered by the lumbar route into the cerebrospinal fluid (CSF) of four patients with malignant leptomeningeal disease. Evidence suggesting uptake of 131I-MCA by tumour sites was seen in scintigrams. Dosimetry calculations were carried out, assuming that a proportion of the administered radionuclide was bound as a thin layer on the CSF surfaces of the meninges. The percentage injected dose and the clearance curves for the head and four spinal segments were obtained by scintigraphy after administration of tracer amounts of 131I-MCA (7-18 MBq). Although radioisotope levels in the central nervous system (CNS) fell, as determined by both external scintillation counting and direct CSF sampling, a marked difference in the measurements developed with respect to time. The ratio of these two measurements reached a maximum of 49:1, 7 days after monoclonal antibody administration. Patients subsequently received therapeutic amounts (870-1600 MBq) of 131I-MCAs, resulting in clinical remissions and prolonged survival. The mean absorbed radiation dose was estimated as 3.9 cGy.MBq-1 to the thoraco-lumbar region of the spine and 0.51 cGy.MBq-1 to the outer surface of the brain. The maximal dose delivered to the surface of the CNS in the region of the spine and brain was 5800 and 600 cGy, respectively.
This study describes a simple and rapid method for the preparation of brush-border membrane vesicles from intestinal biopsies. The specific activities of sucrase, amino peptidase N, and alkaline phosphatase in these vesicles were the same as those in vesicles prepared from intestinal segments. The vesicles from all the regions of the small intestine can transport D-glucose in an Na+-dependent manner. The rates of transport of D-glucose presented here are far higher than previously reported. The method should have a wide applicability to studies of transport mechanisms and the distribution of transport processes within the intestine.
Fifteen patients with neoplastic meningitis received a single intrathecal injection of between 11 and 60 mCi of a 131I radiolabelled monoclonal antibody (MoAb), chosen for its immunoreactivity to tumour. Major toxicity was manifest as nausea, vomiting and headache (7/15 patients), reversible bone marrow suppression (3/8 patients) and seizures (2/15 patients). Nine patients were evaluable for either a tumour or clinical response. Six of these demonstrated an event-free response that was maintained for periods of between 7 and 26 months.
The breath hydrogen test for carbohydrate malabsorption has been proved to be sensitive, specific and noninvasive. This study was performed to determine its applicability in the newborn period. Postprandial hydrogen excretion in the first 5 days of life was measured in 105 full-term normal newborns, who were either artificially or breast fed. Samples of expired air were collected via a nasopharyngeal catheter at 30 min intervals between feeds. Some babies showed no hydrogen production after 5 days, while others produced high (200 parts/10(6] levels. The incidence of hydrogen production increased postnatally--more than 80% of babies produced hydrogen by 5 days of age. None of the babies was unwell or developed frequent or loose stools suggestive of clinical carbohydrate malabsorption. It is therefore postulated that these high hydrogen levels reflect biochemical evidence of clinically insignificant carbohydrate malabsorption in this age group. This study shows clearly that an interfeed interval of 4 h in these babies is insufficient to cause breath hydrogen levels to fall in a predictable way. The ethical and practical difficulties in fasting these infants for longer periods suggest that conventional carbohydrate challenges with breath hydrogen estimations will be difficult in the neonate.
Six patients with neoplastic melanomatous meningitis were studied. The diagnosis of this complication of malignant disease rests on the demonstration of malignant cells within the CSF. The addition of monoclonal antibody immunocytology to conventional techniques significantly improved the diagnostic sensitivity of CSF cytology, allowing for earlier and therefore more effective palliative treatment.
A pilot study was performed to investigate the toxicity and therapeutic effect of radiolabeled antibody administered intrathecally in patients with leptomeningeal tumors. Five patients who failed conventional therapy received between 11 mCi and 40 mCi of radiolabeled antibody. The choice of antibody varied depending on the immunophenotype of the tumor. Therapy was well tolerated generally, with minimal acute toxicity. Four of five patients achieved an objective response to treatment that has been sustained for a period varying from 7 months to 2 years. No clinical signs of chronic toxicity have been observed in patients 1 and 2 years after therapy.
We have developed a psychometric test to assess psychosocial adaptation to diabetes in young people aged from 10 to 17 years. This includes subscales which describe emotional difficulty with, and attitude to, diabetes. The content of the scales was drawn from unstructured discussions with 27 young people with diabetes. The scales were piloted on two further unselected groups of adolescents (n = 50, n = 99) to examine their reliability, validity, and acceptability. Highly significant correlations were found between the results of the scales and measures of psychosocial function (p less than 0.001), parents' perceptions. Performance on the scale also correlated with a number of behaviour variables and differentiated those who were reported to be restricted by their diabetes (p less than 0.005) and those who had had a previous psychiatric referral (p less than 0.05). The scales appear reliable within the constraints of the small population examined.
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A monoclonal antibody (UJ181.4) was labelled with 131I and given intrathecally to a patient who was critically ill with neoplastic meningitis due to a disseminated pineoblastoma. The target antigen had first been demonstrated on tumour cells by immunocytological testing of cerebrospinal fluid (CSF). As a preparation for therapy, a test dose of 131I-UJ181.4 antibody was given simultaneously with a control antibody labelled with 125I. Good evidence of in vivo immunolocalization was obtained by external gamma counting and by analysis of the radiolabels on centrifuged CSF cells. Specificity ratios of between 10:1 and 20:1 were obtained by these methods. A single relatively small therapeutic dose of 131-I (870 MBq) given by the intrathecal route, resulted in a marked clinical improvement and sustained remission for 22 months.
The diagnosis of diabetes mellitus implies a life-time regimented by insulin therapy, dietary manipulations and monitoring glycaemic control. There is also the ever present risk of ketosis and hypoglycaemia and as the child grows up there is an increasing awareness of the later complications of diabetes. This paper is concerned with the care of the child with diabetes from diagnosis, within the context of his home and school, with an emphasis on the emotional response of the child and his family.
Six chordomas (three classic and three chondroid) were examined ultrastructurally and with a panel of monoclonal antibodies. The three classic tumours showed the presence of desmosomes and intermediate filaments on electron microscopy, findings which gave a direct positive correlation when the tumours were stained with monoclonal antibodies against low molecular weight cytokeratin proteins. These results suggest that chordomas are essentially epithelial neoplasms and underline the fact that monoclonal antibodies to cytokeratins cannot be used in the differential diagnosis of classic chordoma vs carcinoma. Furthermore, the epithelial characteristics are lost as the tumour undergoes chondroid differentiation.
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Monoclonal antibody UJ13A, radiolabelled with 131I, was intravenously administered to patients with primary brain tumours. The antigen recognised by UJ13A is present on most neuroectodermally derived tissue. The ratio of uptake in tumour to normal brain, assessed by scintigraphy, improved with time. Maximal tumour uptake occurred between 4 and 48 h. Dynamic and static scintigrams indicated some early sequestration of radiolabelled antibody by the liver. Tumours were surgically resected in seven patients at various intervals after antibody administration showing tissue to blood ratios increasing with time in all parts of the lesion (viable and necrotic tumour, cyst fluid), and in normal brain. The highest tissue to blood ratio in viable tumour was 5.1 at 16 days after injection. In tissues resected 2-3 days after injection there was relatively greater uptake in the viable tumour compared to necrotic tumour and cyst fluid. In contrast, tissues resected later (6-16 days) showed greater uptake in ischaemic tissue than viable tumour, suggesting diffusion was an important factor influencing tumour uptake. The amount of radioactivity per gram of tumour tissue was less than 0.005% of the injected dose. Future studies are needed using different antibodies, antibody fragments and additional methods of optimising delivery.