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Biomedical subjects

A W Craft

Publications and source records attributed to A W Craft.

At least 145 records · Page 8Linked to original sources

Urinary excretion of HMMA and HVA in infants.

Gas chromatography with flame ionisation detection has been used to establish the normal urinary excretion values of homovanillic acid and 4-hydroxy-3-methoxymandelic acid in 808 infants aged 6 months. This study, the essential pre-requisite for population screening for neuroblastoma in babies, reveals a mean homovanillic acid of 10.9 mumol/mmol creatinine and mean 4-hydroxy-3-methoxymandelic of 6.8 mumol/mmol creatinine. The upper 95% confidence interval were 25.5 mumol/mmol creatinine for homovanillic acid and 15.0 mumol/mmol creatinine for 4-hydroxy-3-methoxymandelic. Gas chromatography/mass spectrometry analysis of the 39 samples, (4.8%) with apparent increased excretion of one or both metabolites, revealed that this was, in each case, due to interfering peaks on chromatography.

Chromatography, Gas↗

The long-term effects of treatment on the dental condition of children surviving malignant disease.

Fifty-two long-term survivors of childhood leukemia or solid tumors had a clinical dental examination along with 49 of their sibling. The 52, with an additional 30 examined in a previous study, were studied radiologically with a panoramic tomogram. All children with leukemia had received chemotherapy for 2 or 3 years and irradiation on standard protocols and the solid tumor group had received chemotherapy for 6 to 24 months. There was no difference between siblings and patients for dental caries, gingivitis, and oral hygiene, mouth opening, overjet, and overbite. More solid-tumor patients had abnormal occlusion (P less than 0.02) and those with abnormalities tended to have been treated at an earlier age. Enamel opacities and hypoplasia were more common in patients than siblings and in the leukemia than in the solid tumor group. Sixty-five percent of the children had abnormalities on radiologic examination including failure of the tooth to develop, small crown, hypoplasia of the crown, and abnormal root development. In most cases the radiologic abnormality could be correlated in time with the patient's treatment and a knowledge of the normal time of tooth development. Three teeth extracted during the course of the study were examined histologically and these showed prominent incremental lines which could be correlated in time with vincristine treatment.

Adolescent↗

Measles in children who have malignant disease.

A review study examined the clinical course of measles diagnosed in children being treated for malignant disease in Newcastle upon Tyne during 1973-86. Of the 17 cases diagnosed, five were fatal. Factors associated with a favourable outcome were a typical rash and Koplik's spots, which were accompanied by a detectable serum antibody response and the disappearance of measles giant cells from nasopharyngeal secretions. Pneumonitis severe enough to require assisted ventilation was invariably fatal. Pneumonitis and encephalitis were the main complications. Treatment included immunoglobulin, interferon, and ribavirin, but none could clearly be shown to be effective. The comparatively low mortality in this series may have been due to the extensive use of the fluorescent antibody technique in Newcastle during the study period and therefore detection of less severe cases as compared with other reports.

Child↗

Pharmacokinetics of oral and intramuscular methotrexate in children with acute lymphoblastic leukaemia.

Repeated methotrexate absorption studies were performed under standard conditions in 127 children receiving either oral or intramuscular methotrexate for acute lymphoblastic leukaemia. There was marked variability in peak concentration, area under the serum concentration curve and clearance both between patients and in repeated studies on the same patient. Although the intramuscular route produced higher serum concentrations and AUC than the oral route, variability within and between patients was considerable and was most marked at higher concentrations. Neither age or sex could account for variation in methotrexate absorption or clearance. Intramuscular methotrexate, although producing higher serum concentrations and AUC, does not reduce the variability observed with oral administration. Prediction of subsequent methotrexate concentrations from the knowledge of one absorption profile is not possible.

Administration, Oral↗

X-ray sensitivity of fibroblasts from patients with hereditary retinoblastoma and their families.

The in vitro response to X-irradiation of cultured human fibroblasts was studied using a colony forming assay. A comprehensive reference range was established, giving a median D0 value of 98.5 cGy with an interquartile range of 86.5-110.5 cGy. Cells from 3 retinoblastoma family pedigrees were studied and the cell survival after exposure to X-rays was compared between affected (11 samples) and unaffected (26 samples) family members. No significant differences in response to ionising radiation were found between the controls, the affected and the unaffected members of the 3 families. The affected members had a median D0 of 97.5 cGy (interquartile range 87.5-107.5 cGy) and the unaffected members had a median D0 of 102 cGy (interquartile range 93-111 cGy). Thus radiosensitivity is not a useful marker for the detection of the retinoblastoma gene.

Adolescent↗

The Northern region Children's malignant disease registry 1968-82: incidence and survival.

All cases of childhood cancer diagnosed before the 15th birthday in the years 1968-1982 and resident in the Northern Health Authority region have been registered. There were 1171 registrations and only two have been completely lost to follow up. The overall annual incidence of cancer was 107.1 per million children, similar to previously reported figures. There was no significant change in the rate over the 15 year period either for all cancers or individual cancer types. Eighty six percent of registrations had central review of pathological material. There has been a significant move towards centralisation of care over the 15 years and a significant improvement in survival over the three quinquennia for all cases and for most individual types. High white blood cell count at presentation was confirmed as a bad prognostic feature in children with acute lymphoblastic leukaemia (ALL). Children treated for ALL in a peripheral hospital had a significantly worse survival than those referred to a specialist centre. Survival rates were calculated for all of the major types of malignancy. The registry includes four sibling pairs with cancer and one family with three siblings affected. Ten children developed secondary primary tumours.

Adolescent↗

Serological study of Pneumocystis carinii infection in the absence of immunosuppression.

Serum samples from 145 children with no known immunosuppressive illness were examined by indirect immunofluorescence for antibody to Pneumocystis carinii. Positive antibody titres (greater than or equal to 1:8 dilution) were found in 69 children (48%). Antibody could not be detected in the remaining children. Previous studies have shown that at least 75% of children have antibodies to P. carinii by the age of 4 years. This study shows a lower percentage of children with detectable antibody. This may be related to geographical variation of antigen or possibly to the widespread use of co-trimoxazole.

Adolescent↗

Chromosomes of metastatic retinoblastoma.

Chromosomal abnormalities were detected in the bone marrow of a girl with disseminated retinoblastoma. One of these abnormalities, i(6p), is characteristic of primary retinoblastoma and its presence confirmed the diagnosis of bone marrow infiltration with retinoblastoma. This approach could be extended to study other tumours of childhood.

Biopsy↗

Cytogenic investigations in the assessment of response to treatment in neuroblastoma.

In a patient with stage IV disseminated neuroblastoma treated by chemotherapy extensive cytogenetic investigations were performed on the residual primary tumour and bone marrow immediately before myeloablative treatment and autologous marrow rescue. Two abnormal clones both showing lp+, a characteristic abnormality of neuroblastoma, were detected in cells from the residual primary tumour, providing direct evidence of persisting viable tumour. Such investigations should be a routine part of the assessment of response to treatment in patients with neuroblastoma, and could be extended to others in whom "second look" surgery is performed.

Adrenal Gland Neoplasms↗

Virus infections in childhood malignant disease.

The viruses isolated during infective episodes over a 5-year period of 93 children with acute lymphoblastic leukemia (ALL) and 107 children with other malignancies have been studied. Viruses were identified by the fluorescent antibody technique (FAT), electron microscopy, and culture. Viruses were isolated on 204 occasions. Rhinovirus and RSV occurred significantly more often in the patients with ALL, and adenovirus more commonly in the solid tumor patients. Viruses were responsible for 4 of the 69 deaths. Multiple different virus isolation during the same infective episode was significantly more common than in a control group. Where paired sera were available, only 10 out of 27 children showed at least a fourfold rise to the isolated virus. A rise in complement-fixing antibody is confirmed as a very unreliable method of detecting virus infection in immunosuppressed children. Viruses are important pathogens in children with cancer and assume greater relevance now that over 60% of malignant disease in childhood can be cured.

Child↗

Multicentre study of piroxicam versus naproxen in juvenile chronic arthritis, with special reference to problem areas in clinical trials of nonsteroidal anti-inflammatory drugs in childhood.

Clinical trials of nonsteroidal anti-inflammatory drugs (NSAIDs) are necessary in juvenile chronic arthritis (JCA) but pose certain problems highlighted and discussed in this study, including recruitment, the assessment of efficacy, and the heterogeneity of the disease. In a multicentre 8-week double-blind cross-over study using the double-dummy technique, piroxicam was compared with naproxen in 47 children with seronegative JCA aged 5-16 years. No significant difference between the two treatments was found in either the clinical variables measured or the parent/patient and physician preference at the end of the study. Side-effect profiles of the two drugs were similar, mainly gastrointestinal disturbances. Piroxicam may be a useful alternative NSAID in JCA, particularly in view of its once-daily dosage.

Adolescent↗

Interferon responses of peripheral blood mononuclear cells from normal and leukaemic children.

Human peripheral blood mononuclear cell cultures (PBMC) stimulated with Sendai virus or K562 cells produce a mixture of interferons. Temperature and pH stability characteristics and reactions with monospecific antibodies indicate that PBMC cultures from adults produce interferons alpha and gamma in approximately equal proportions. PBMC cultures from children produce lower levels of interferons with a higher proportion of type alpha. The ability of PBMC cultures from children with acute lymphoblastic leukaemia (ALL) to produce interferon was determined. Little or no gamma interferon was induced by either Sendai virus or K562 cells. Cultures from some children with ALL produced alpha interferon but mean levels were significantly lower than from normal children. A group of older children with ALL who had completed their course of therapy and were off treatment produced levels of interferon indistinguishable from those of normal children. This in vitro deficit, possibly induced by chemotherapy, may reflect an in vivo deficit and may contribute to the impaired handling of viruses seen in children being treated for ALL.

Adolescent↗

Intellect after malignancy.

A previous study has shown that significant intellectual deficits exist in children treated for leukaemia but not in those with solid tumours. Unexpectedly, the deficits had not increased in the two years since the original study, suggesting that the nadir had already been reached five years after diagnosis.

Child↗

Continuous ECG monitoring of children with cancer receiving domperidone.

Domperidone is an effective antiemetic for children receiving cytotoxic therapy. There have been reports of cardiac arrest in older patients associated with domperidone. We carried out continuous ECG monitoring of 18 children receiving domperidone intravenously in a dose of 1 mg/kg body weight. No serious dysrhythmias were noted during 379 h of recording. Single premature beats, transient sinus pauses, and nodal block were occasionally associated with vomiting and were no more common than would be expected in a population of normal children.

Adolescent↗