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Biomedical subjects

M Hewitt

Publications and source records attributed to M Hewitt.

At least 19 recordsLinked to original sources
PubMed1996

Glycophorin A mutations and risk of secondary leukaemia in patients treated for childhood acute lymphoblastic leukaemia.

Survivors of child acute lymphoblastic leukaemia (ALL) have a higher than expected risk of developing secondary acute myeloid leukaemia (AML). The glycophorin A (GPA) mutation assay measures the frequency of variant NO and NN erythrocytes in MN heterozygotes. A raised variant frequency (Vf) has been shown in patients treated with chemotherapy known to be at risk of secondary leukaemia. ALL patients were investigated for increased Vf using the GPA assay. Vfs at diagnosis were not significantly different from controls (NO Vf P = 0.193; NN Vf P = 0.790). During treatment Vfs increased significantly (No Vf P = 0.001; NN Vf P = 0.001). NO Vf returned to control values (P = 0.169) within 5 years from diagnosis but NN Vf remained significantly raised (P = 0.014). Three study patients developed secondary AML. At diagnosis of AML all three had significantly increased Vf. The first had a significantly raised Vf at routine follow-up 19 years following diagnosis of ALL then developed AML 3.5 years later. The second had a significantly raised NN Vf at diagnosis of ALL indicating possibly prior exposure to a mutagen or defective DNA repair involving erythroid stem cells. We conclude that a raised Vf detected by the GPA assay can act as a marker for the development of secondary induced leukaemia and can be used to screen individuals at a known high risk of this complication.

Acute Disease↗
PubMed1994

Do mutations at the glycophorin A locus in patients treated for childhood Hodgkin's disease predict secondary leukaemia?

Childhood Hodgkin's disease has a high cure rate but second cancers are common, related to treatment and perhaps genetic predisposition. The glycophorin A (GPA) mutation assay measures the frequency of NO and NN mutant erythrocytes of MN blood-group heterozygous individuals. Mutant frequencies in Hodgkin's disease patients were compared with controls. No significant difference from controls was found pretreatment or in patients treated with radiotherapy only. Patients who received chemotherapy had a significantly increased frequency (total mutation frequency per 10(6) cells: 31 vs 11, p < 0.001), which may be relevant to their known increased risk of secondary leukaemia.

Adolescent↗
PubMed1993

The efficacy and safety of ondansetron in the prophylaxis of cancer-chemotherapy induced nausea and vomiting in children.

The management of chemotherapy induced emesis presents a major difficulty in the paediatric population. Ondansetron is a 5-HT3 antagonist and its antiemetic properties have been established in adults receiving chemotherapy. Experience in the treatment of children, however, is limited. There is no standard comparative antiemetic in paediatric practice, so this European, multi-centred study aimed to assess the clinical efficacy and safety of ondansetron in a large cohort of children receiving a range of emetogenic chemotherapy regimens for malignant disease. Two hundred patients were entered into the study, of whom 183 fulfilled entry criteria. Forty per cent (10/25) of patients receiving cisplatin, 68% (27/40) receiving ifosfamide and 70% (83/118) receiving other drugs had less than 3 emetic episodes (vomit or retch) during their worst 24 hours of chemotherapy. The number of days without vomiting or retching during and shortly after receiving chemotherapy was also related to the emetic potential of the agents in the regimen: cisplatin 82/182 (45%), ifosfamide 137/213 (64%) and other agents 430/566 (76%). The control of nausea appeared better than that of emesis in each of the sub-groups analysed. Ondansetron was safe, well tolerated and effective in the prevention of vomiting in children receiving a wide variety of chemotherapy regimens.

Antineoplastic Agents↗
PubMed1992

The assessment of in vivo somatic mutations in survivors of childhood malignancy.

The assessment of chromosomal mutations in children may provide information about aetiology and risk of second malignancies. A somatic cell mutation assay which determines variant erythrocytes lacking expression of an allelic form of the sialoglycoprotein, glycophorin A, was applied to samples from children before and after receiving potentially genotoxic therapy. Fifty-six children who had received treatment for their malignancy, 15 with malignancy but prior to treatment and 43 control children were assessed for the presence of Nø and NN mutant variant red cells. Control children had mean (s.d.) Nø and NN variant frequencies (Vf) of 9.5 (7.0) and 5.8 (3.3) x 10(6) erythrocytes respectively. Comparison between pre-treatment and control groups demonstrated that prior to chemotherapy, patients with paediatric malignancy do not have mutant frequencies significantly different from the normal population. Children who had received chemotherapy, with or without radiotherapy, showed a significant elevation of both Nø and NN variants over 10 years from the end of treatment. Exposure of children to radiotherapy or known chemical mutagens leads to an increased frequency of variant erythrocytes which is probably the result of in vivo somatic cell mutations. The long term implications have yet to be determined.

Adolescent↗
PubMed1991

A new index of aggregation for animal counts.

A new index is described that is especially appropriate for measuring the aggregation of entomological data in the form of counts per sample unit and that can make use of spatial information when it is available. Calculation of the index is based on a comparison of the effort required of individuals in a sample to achieve complete crowding with that to achieve complete randomness. The power of tests of randomness based on this index is found to be greater than those based on the index of dispersion, especially when spatial information is available.

Animals↗
PubMed1991

Effective emetic control during conditioning of children for bone marrow transplantation using ondansetron, a 5-HT3 antagonist.

Preparation for bone marrow transplantation (BMT) uses the extremely emetogenic combination of chemotherapy and total body irradiation (TBI). Ondansetron is a selective 5-HT3 antagonist and has clear anti-emetic capabilities. The efficacy of the drug was assessed in 15 children (aged 2-17 years) who received high dose cyclophosphamide (on days -6 and -5) and TBI (days -3 to 0 inclusive). During days -6 to -4 when the emetic effect of cyclophosphamide would be most pronounced, 12 of the 15 patients (80%) had fewer than five emetic episodes during their worst 24-h period, 11 (73%) had fewer than three vomits whilst nine (60%) experienced no vomiting or retching. Eleven patients progressed to TBI and 10 (91%) had fewer than five emetic events in the worst 24-h period (days -3 to +2), six (55%) had no vomiting at all. Of 100 evaluable 'patient-days' 83 (83%) were without any vomiting or retching and a further 10 'patient-days' had only one or two emetic episodes. There were no significant side-effects noted and in particular no extrapyramidal reactions. Headaches and constipation, which have been seen in adult studies, were not reported by patient or parent on any of the study days and transient elevation of liver enzymes were noted in only two patients. Ondansetron has a major role in preparing patients for BMT.

Adolescent↗
PubMed1989

Kawasaki disease in siblings.

We report a case of mucocutaneous lymph node syndrome, which was diagnosed in a 13 month old boy two years after the death of his sister from the same disease.

Coronary Vessels↗
PubMed1989

Incidence of contraindications to immunisation.

A cohort of 522 children entering primary school were reviewed for contraindications to immunisation. Every child in the group would have been eligible to receive diphtheria, tetanus, polio, and measles immunisation if the current (1988) Department of Health and Social Security (DHSS) guidelines had been followed. Only 2.5% of the cohort met the DHSS contraindications to pertussis immunisation.

Child↗