Biomedical subjects
Publications and source records attributed to A W Craft.
A child with a primary malignant cardiac tumor prompted a review of all 13 cases reported in Great Britain from 1962-1983. Only 4 definitely malignant tumors were identified, giving an incidence of between 1 in 38 and 1 in 90 x 10(6). All 4 patients died without evidence of metastases. Cardiac transplantation should be considered.
The gene for hereditary retinoblastoma (Rb), an autosomal dominant trait localized to the long arm of chromosome 13, is linked to the locus for the enzyme esterase D (EsD). We analyzed a three-generation family that demonstrates cosegregation of alleles at the EsD locus and the Rb locus. This kindred yields a logarithm of the odds ratio (LOD) score of 2.46 at a recombination fraction (0) of 0.0. When combined with five other recently reported families, the resulting maximum score was 11.08 at 0 = 0.0. This combined LOD score and the lack of demonstrable crossovers in more than 65 individuals indicate that predictions of the Rb gene carrier state based on EsD genotyping are at least 90% accurate.
Serum methotrexate concentrations have been measured in 28 children with acute lymphoblastic leukaemia (ALL) following PO administration under standard conditions. Small-intestinal transit time, measured by the time taken for lactulose to pass from mouth to caecum, has been related with methotrexate absorption parameters. Small intestinal transit times ranged from 30 to 240 min. Children with longer transit times had later times of peak methotrexate concentration and tended to have a more erratic methotrexate absorption profile with two peaks. There appears to be an optimal transit time between 90 and 105 min for methotrexate absorption, with both faster and slower small-intestinal transit times producing lower peak concentrations as a fraction of the dose.
Fifteen children with acute lymphoblastic leukaemia (ALL) in remission receiving maintenance chemotherapy and 12 ALL patients off treatment and in remission were tested for natural killer (NK) cell activity in vitro. Compared with a control population the children with ALL receiving maintenance chemotherapy had low levels of NK cell activity. This effect was not due to a specific reduction in NK cell numbers since proportions of mononuclear cells detected by the monoclonal antibodies HNK-1 (Leu-7) and Leu-11a were normal. Furthermore NK cell activity in patients could only be partially increased by pre-incubation of effector cells with interferon (alpha IFN). These studies confirm the lack of NK cell activity in children with ALL and show that this phenomenon is directly related to functional NK cell impairment. Our study has further shown that this effect is transient since ALL patients off treatment and in remission showed normal levels and augmentation of NK cell activity.
A 5 year old boy developed an implantation dermoid tumour after a lumbar puncture in infancy. A survey of senior paediatricians has shown it to be common practice to use an unstiletted needle for lumbar puncture in small children. A stiletted needle is recommended for all such procedures.
Nasal concentrations of leucocyte interferon measured immunoradiometrically were appreciably higher in children infected with influenza viruses than those infected with paramyxoviruses. Regardless of the infecting virus, leukaemic children produced normal amounts of interferon, but this appeared to have little effect on the duration of excretion of virus.
The place of residence of all cases of childhood cancer occurring in the Northern Region from 1968 to 1982 has been analysed by electoral wards. The wards have been ranked according to rate and Poisson probability. Both rankings show a wide geographical scatter throughout the region of areas with an apparent excess incidence of cancer. These areas are not confined to the Cumbrian coast.
Chronic arthritis in children is uncommon. Careful clinical and laboratory studies over many years have defined subgroups of disease that have their characteristic pattern of joint development and disease course. The prognosis for children who have arthritis is generally excellent but it may take years of care by a variety of specialists to achieve optimum results.
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A full dental examination on 64 children aged from 3 to 20 years who were in long term remission from malignant disease showed normal facial growth, caries incidence, and periodontal indices. There was increased incidence of hypodontia and hypoplasia which in some could be ascribed to the original disease or its treatment.
Small bowel function before, during, and after treatment for acute lymphoblastic leukaemia was studied in 26 children. A significant impairment of D-xylose absorption was found during treatment. Permeability studies showed a significant decrease in mannitol and a significant increase in lactulose concentrations; five of 20 children tested had evidence of lactose malabsorption, three of whom were symptomatic. Intestinal function abnormalities were greater in children whose methotrexate treatments were separated by 7 day than by 16 day intervals. Only five (19%) children had no abnormal tests. Abnormalities of small bowel function may be treatment induced and this has implications for morbidity from gastrointestinal symptoms, impairment of the mucosal barrier, and malabsorption of both nutrients and drugs leading to malnutrition and suboptimal drug concentrations.
A child is described who, following surgery and irradiation for malignant choroid plexus papilloma at the age of 11 months, developed three further tumors: A benign myxofibroma of the cranium at the age of 3 1/2 years, an undifferentiated anaplastic tumor of his clavicle at 7 1/2 years, and a chondroblastic osteogenic sarcoma of his pelvis at the age of 12 years. There was no apparent genetic predispositions to malignancy. The latter three neoplasms may have originated either in, or at the edge of, the original radiotherapy field, suggesting that the child has a particular susceptibility to the oncogenic potential of radiotherapy.
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All children aged under 15 years admitted to hospital in Newcastle upon Tyne between 1974 and 1981 with a diagnosis of poisoning were studied. After the introduction in 1976 of child resistant containers for salicylates and paracetamol, salicylate poisonings fell dramatically. The other most important medicines to cause poisoning in young children were tricyclic antidepressants, benzodiazapines, Lomotil (diphenoxylate and atropine), and iron preparations; these should also be packaged in child resistant containers by regulation. Few children had symptoms after poisoning with household products, but bleach, turpentine, and paraffin might also be packaged in child resistant containers. The numbers of adolescent girls admitted after deliberate self poisoning and of teenage boys admitted after ingestion of alcohol increased over the study period.
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The pharmacokinetics of metoclopramide have been studied in nine children receiving the drug as prophylaxis for cytotoxic induced vomiting. Plasma concentrations of metoclopramide have also been studied in three children with dystonic reactions to the drug. The pharmacokinetics in children were similar to those reported in healthy adults. There was no difference in the plasma concentration of metoclopramide of children with dystonia when compared to those without this adverse effect. Kinetic differences in childhood do not explain the occurrence of dystonia, which in the individual appears to be related to factors other than plasma drug concentrations.
The deaths of 99 children under 5 years of age were studied through the coroners' records. Sixty nine deaths were caused by medicines--most of which were prescribed for mother, were recently dispensed, and currently in use. Household products accounted for 11 deaths, lead poisoning for 6, carbon monoxide for 5 and 'medical mishaps' for 8. Prevention lies in both education and more effective and selective use of child resistant containers.