Biomedical subjects
Publications and source records attributed to D Pickering.
An A-to-G transition in the second intron was the sole mutation detected in four Yupik Eskimo patients with salt-wasting congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency. Allele-specific hybridization should be an efficient means of performing prenatal diagnosis of the disease in this highly inbred population.
To gain insight into the molecular mechanism underlying melatonin binding and signal transduction in the chick brain, we have investigated the role of -SH groups, using a sulfhydryl alkylating reagent N-ethylmaleimide (NEM). At least two -SH groups are involved in the formation of the receptor-G protein complex: one is sensitive to and the other relatively insensitive to NEM. Alkylation of the sensitive group selectively abolishes high affinity binding of 2-[125I]iodomelatonin ([125I]MEL), similar to the effect induced by GTP, thus leading to a complete loss of sensitivity to nucleotides. Modification of both groups causes a marked reduction in binding capacity. Agonists with high affinity, but not other compounds with low affinity for the melatonin receptor, protect against alkylation by NEM. GTP gamma s does not significantly alter the reactivity of -SH groups towards NEM, but agonist-protected receptors remain sensitive to this nucleotide. Moreover, NEM pretreatment blocks the inhibitory effect of melatonin on forskolin-stimulated adenylate cyclase activity in chick brain. These data suggest that the -SH group modulating agonist affinity may lie within the coupling domain between the receptor and G protein but outside of the GTP binding site. In addition, sulfhydryl groups are essential for melatonin binding and signal transduction in chick brain.
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In a patient with recurrent grade IV glioma of the brain resistant to conventional treatment an antibody guided isotopic scan showed uptake by the tumour of a monoclonal antibody (9A) that was developed against epidermal growth factor receptor but cross reacted with blood group A antigen. As a therapeutic attempt antibody labelled with 1665 MBq (45.0 mCi) iodine-131 was delivered to the tumour area by infusion into the internal carotid artery. Computed tomography showed regression of the tumour after treatment, and an appreciable and sustained clinical improvement was noted without any toxicity. Delivery of irradiation guided by monoclonal antibody delivered by arterial infusion of the tumour area may be of clinical value in the treatment of brain gliomas resistant to conventional forms of treatment.
This study examined (a) how parents of autistic children, parents of other handicapped children, and parents of nonhandicapped children rate, as a whole, acceptability of time-out, differential reinforcement, overcorrection, and shock as treatments for self-injurious behavior, and (b) whether these parents show differences, as groups, in ratings of these treatments. On the Treatment Evaluation Inventory, all groups consistently rated differential reinforcement, time-out, and overcorrection as acceptable and shock as unacceptable. Differential reinforcement was consistently rated as the most acceptable, but the groups differed in ratings of acceptability of other treatments. On the Semantic Differential, ratings of differential reinforcement, overcorrection, and time-out did not differ. However, shock was consistently rated as the most potent and active of treatments as well as the most unacceptable. The implications of these findings for treatment of autistic and other handicapped children are discussed.
Abdominal lymphoscintigraphy is a quick, easy, cheap and relatively non-invasive technique. In our study it appeared to be as accurate as lymphography, giving a positive correlation in 25 out of 32 patients (78%). In 11% of cases the lymphoscintigram detected an abnormality of lymph node function before macroscopic morphological change was seen in the lymphogram, indicating that in some instances lymphoscintigraphy is more sensitive than lymphography. The reason for this is unknown, although possible mechanisms are discussed and these are the subject of current further study. We believe this to be the first report of lymphoscintigraphy being more sensitive than lymphography for detecting lymph node disease.
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Administration of oral indomethacin to treat cardiorespiratory failure in 7 low birthweight infants, after failure of conventional therapy, produced an improvement in only 2 infants. These infants had a higher birthweight than the group as a whole. Surgical ligation, rather than oral indomethacin, may be the treatment of choice for persistent ductus arteriosus in very low birthweight infants.
Surgical closure of a patent ductus arteriosus was performed in 8 low birthweight infants suffering from cardiorespiratory failure secondary to a large left-to-right shunt. Mortality from the operation was nil, but only 4 (50%) ultimately survived. Earlier intervention may reduce mortality in these high-risk infants.
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In this report we describe a child who had an apical systolic click and murmur, as well as widespread cutaneous neurofibromatosis. We were not able to show an anatomical basis for the click and murmur.
Endomyocardial biopsy was attempted in 18 children aged 5 months to 15 years with 82% success. Biopsies obtained from 15 children were examined by light and electron microscope making positive morphological diagnoses in 3 cases. The biopsy findings were actively helpful in 7 other cases, which contrasts with experience in adult biopsy series. This is a low risk procedure which does not add to the hazards of cardiac catheterization in children.
Persistent ductus arteriosus (PDA) complicated the clinical course in 45 (15%) of 299 babies with the respiratory distress syndrome (RDS) presenting over a 3-year period. The incidence of PDA complicating RDS rose with decreasing birthweight and was highest in babies with severe RDS as judged by the use of assisted ventilation. In babies with a birthweight of less than 1500 g, PDA occurred as a complication of RDS in 25% of cases. In babies who recieved intermittent positive pressure ventilation (IPPV) for management of RDS, the incidence of PDA was 35%. Overall mortality for babies with RDS was 17%; when PDA occurred as a complication mortality was 31%. In survivors, spontaneous closure of the PDA occurred in all except one infant. The development of signs of PDA in 19 babies either necessitated a renewal of IPPV or prevented "weaning" from IPPV or from continuous positive airways pressure. 9 (47%) of these babies died, 8 of them after the first week of life. The frequency of PDA complicating RDS and the relatively high mortality in this conservatively-treated group of babies is emphasized. The incidence reported here is likely to increase with the increased survival of very low birthweight infants with severe RDS. The high incidence of late deaths in babies who develop signs of PDA associated with an inability to wean from assisted ventilation suggests that early surgical ligation of the PDA in these babies should be considered. The results of a conservative approach to management of these infants are presented.
A 22-month-old girl with cystinotic rickets was given 1 microgram 1,25-dihydroxycholecalciferol (1,25-DHCC) daily in addition to standard treatment. Her rickets healed and linear growth rate appeared to increase. It is suggested that the effect of 1,25-DHCC and its metabolically active analogues on cystinotic rickets should be further studied.