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Biomedical subjects

M G Mott

Publications and source records attributed to M G Mott.

At least 19 recordsLinked to original sources
PubMed1996

Variation in survival of children with cancer within a region of the United Kingdom.

BACKGROUND: A population-based study of survival of 678 children, age less than 15 years, diagnosed with cancer in the Southwest region of the United Kingdom showed an improvement in 5-year survival from 53% between 1976 and 1980 to 64% between 1981 and 1985 (P = 0.008). Survival varied significantly among the five counties that make up the region (P = 0.0008); the differences were greatest for central nervous system (CNS) tumors. METHODS: The expertise of local hospitals and entrance into national trials was examined. The region has nine hospitals acting as primary treatment hospitals for children with cancer, two neurosurgical units, and one regional oncology unit. Four of the primary hospitals saw more than six children per year and were designated "large" centers. Five saw fewer than six patients per year and were designated "small" hospitals. RESULTS: There was a significant difference in survival of patients according to the number of patients treated per year per hospital. A hospital that treated fewer than six patients per year was designated "small" and six or more designated "large." At 5 years, patients with CNS tumors experienced a 58% survival rate in large hospitals and a 41% survival rate in small hospitals. (P = 0.03). The rate of entrance into trials for all malignancies did not differ between large (30%) and small (27%) centers. Only 5% of children with CNS tumors were placed on national trials. There was no difference in survival rates for CNS tumors in the two neurosurgical centers. CONCLUSIONS: There were significant differences in survival by county for children with cancer, especially those with CNS tumors. In the first half of the study decade, in hospitals treating fewer than six cases of childhood cancer per year, children with CNS tumors were rarely placed on national protocols and did poorly.

Adolescent↗
PubMed1996

Radon in Devon and Cornwall and paediatric malignancies.

Exposure to radon in dwellings may cause cancer including paediatric malignancies. Devon and Cornwall have the highest exposure to radon of the counties of England. However, within these counties there is considerable variation in exposure. Exposure to radon in the 283 postcode sectors of the two counties has been published. The incidence of childhood malignancies between 1976 and 1985 was studied to compare postcode sectors of radon exposures > or = 100 Bq/m3 with sectors < 100 Bq/m3. No significant difference in the incidence rate of 106.7 per million child years in the high radon postcode sectors and 121.7 in the low (P = 0.29) was found. When the incidences of individual tumours were examined, a significantly increased rate of neuroblastoma (P = 0.02) and a non-significant increased rate of acute myeloid leukaemia were found in the high exposure postcode sectors. No association between radon exposure and overall rate of childhood malignancy was found.

Acute Disease↗
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↗
PubMed1996

Early identification of anthracycline cardiomyopathy: possibilities and implications.

The number of survivors of childhood cancer affected by anthracycline cardiomyopathy is steadily increasing, despite efforts to limit cardiotoxicity by dose restriction. Cardiac function was evaluated prospectively in 125 children during treatment to attempt to identify individual susceptibilities to cardiotoxicity and hence any potential for treatment modification. Left ventricular shortening fraction was used as an index of cardiotoxicity. Shortening fraction declined as cumulative anthracycline dose increased, at an average rate of 1% per 100 mg/m2. Six patients (5%) developed heart failure. Twenty four patients (19%) had abnormal shortening fraction (< 30%) by the end of treatment, and their rate of fall of shortening fraction was significantly steeper throughout treatment than in patients finishing with normal function (shortening fraction > or = 30%). This differential susceptibility to cardiotoxicity was apparent from very early in treatment, interquartile ranges of the two shortening fraction groups separating at doses > 200 mg/m2. Patients at high risk of risk of important anthracycline cardiotoxicity may be identifiable early in treatment by regular and careful monitoring of shortening fraction. However, frequent assessment is required and this has significant resource implications.

Antibiotics, Antineoplastic↗
PubMed1995

Prolonged survival following multiple thoracotomies for metastatic hepatoblastoma.

A 14-month-old boy presented with hepatoblastoma, which was completely excised. He had pulmonary metastases, diagnosed 1 year later, treated with chemotherapy followed by resection at age 2 1/2 years. At the age of 3 1/2 years a further metastasis was shown on CT scan and this was resected. Two further metastses were resected at ages 4 1/2 and 5 1/2 years. At age 9 1/2 he had a further isolated pulmonary metastasis resected and is again disease-free more than 30 months from the last thoracotomy. Prolonged survival following metastatic hepatoblastoma can be achieved with repeated thoracotomies, especially if the first recurrence is more than 6 months from diagnosis and the number of metastases is small. Follow-up examinations should be both radiological and with serum alpha fetaprotein (S alpha FP).

Hepatoblastoma↗
PubMed1995

Neoplasia in childhood--25 years of progress.

BACKGROUND: Several factors have contributed to the improved prognosis for the survival and quality of life of children with cancer. Childhood tumours tend to have their origin in intrinsic genetic abnormalities, and are usually disseminated by the time of diagnosis. As a result, conventional treatments, such as ablative surgery and/or radiotherapy (the effects of which are detrimental to the growth and development of normal tissues), are rarely successful. The advent of effective combination chemotherapy, given as an adjuvant to eradicate micrometastases, has led also to the dramatic regression of inoperable primary tumours. Subsequent surgery often enables complete resection without the need for radiotherapy. Primary surgery is now used to obtain sufficient tissue to make a precise diagnosis, and recently developed molecular techniques make this possible with great precision from needle biopsies in many instances. The development of an effective treatment regimen is the single most important prognostic factor. This also permits analysis of the differences between successfully treated groups and those not cured by standard treatment. These prognostic factors usually have a biological basis that is identifiable at diagnosis, allowing stratification of treatments and further development. Some of the worst prognosis cases on past standard therapy, such as B-cell acute lymphoblastic leukaemia, have an excellent prognosis when specific treatment regimens are designed to fit their particular characteristics. The finding of specific genetic mutations underlying many childhood tumours may now provide an 'Achilles heel' to enable the development of highly specific therapies that are relatively non-toxic to the normal tissues undergoing rapid growth and development during childhood. The rarity of childhood cancer and the need for multidisciplinary management make it impossible for the ordinary district hospital to deliver optimal treatment, though 'maintenance' treatment and follow-up can be delivered locally as part of 'shared care' with a regional centre. These centres are members of the U.K. Children's Cancer Study Group which was formed in 1977 and now treats 75%. of all cases of childhood malignancy, with sufficient numbers to run randomized clinical trials for most tumour types, often in collaboration with other national paediatric oncology groups in Europe and the U.S.A. CONCLUSION: Children with cancer are likely to be major beneficiaries from the recent advances in the understanding of neoplasia, many of which stem from work on paediatric malignancies. It is therefore important and mutually advantageous to foster and maintain close links with mainstream 'adult' oncology and with the cancer research institutions.

Adolescent↗
PubMed1995

Left ventricular diastolic function in children measured by Doppler echocardiography: normal values and relation with growth.

OBJECTIVES: To determine normal values for variables of left ventricular diastolic function in children measured by Doppler echocardiography and their relations to body surface area (BSA). BACKGROUND: There is increasing interest in echocardiographic assessment of left ventricular diastolic function in children but normal data for children are limited. METHODS: Assessment of left ventricular diastolic function was performed in 130 normal participants (aged from 2.4 months to 19.6 years) from their transmitral flow patterns obtained by pulsed wave Doppler echocardiography. RESULTS: Centile charts for commonly used left ventricular diastolic functional variables plotted against BSA are presented. Peak early diastolic filling velocity and atrial phase filling velocity integral were independent of BSA. Although most other filling indices showed strong relations with BSA, some had more curvilinear relations with BSA due to additional interactions with heart rate. The increase in left ventricular filling with growth is largely achieved by an increase in the early "passive" contribution to filling. The slower heart rates of older children are associated with lower atrial phase filling velocities but increased filling time, so the atrial contribution to filling remains relatively constant. CONCLUSIONS: Normal values of many left ventricular diastolic function variables change with growth in children and cannot be extrapolated from adult data. The data presented are suitable for use in size matched matched comparative studies of left ventricular function in children. Careful standardisation of echocardiographic protocols is necessary to ensure the validity of any comparisons.

Adolescent↗
PubMed1995

Left ventricular diastolic function after anthracycline chemotherapy in childhood: relation with systolic function, symptoms, and pathophysiology.

OBJECTIVES: To examine left ventricular (LV) diastolic function in patients previously treated with anthracycline drugs for childhood malignancy. To consider clinical relevance, relations with systolic dysfunction, and the pathophysiology of anthracycline cardiotoxicity. DESIGN: Cross sectional echocardiographic study of LV function. SETTING: Supraregional centre for paediatric cardiology, principal centre for the treatment of childhood malignancy in southwest England. PATIENTS: 226 of 236 patients surviving between 6.5 months and 17 (median 5.3) years from initial anthracycline treatment for childhood malignancy attended for clinical and echocardiographic examination. Cumulative anthracycline doses were between 50 and 750 (median 300) mg/m2. 22 patients had also received cardiac irradiation. METHODS: Detailed assessment of transmitral diastolic pulsed wave Doppler flow patterns along with LV dimensions and systolic function measured by M mode echocardiography. MAIN OUTCOME MEASURES: Peak early (E) and atrial (A) phase filling velocities and EA ratio, time and acceleration and deceleration to and from peak E velocity, velocity integrals and ratio, isovolumic relaxation time (IVRT), and heart rate were measured. Results were examined in relation to LV cavity and posterior wall dimensions and shortening fraction (SF), and compared with paired control data matched for body surface area. RESULTS: Eleven (5%) patients had abnormal effort tolerance. Fifty one (23%) had SF < 30% and SF was inversely correlated with cumulative dose and time from treatment. The relative risk of symptomatic cardiac failure was greatly increased by prior irradiation; > 60% of irradiated patients who received > 400 mg/m2 of anthracycline were symptomatic. Early diastolic filling was relatively normal or enhanced at low anthracycline doses or when SF was preserved, with a shorter IVRT and increased atrial phase filling. Early filling was reduced at higher doses or with reduced SF, with longer IVRT and a further increase in atrial phase filling. A more "restrictive" pattern of diastolic filling (with high E and low A velocities) was seen in some patients, particularly after cardiac irradiation. CONCLUSIONS: Significant abnormalities of diastolic function are associated with anthracycline induced cardiac damage. These are not linearly related to anthracycline dose but appear to reflect the underlying myocardial pathophysiology associated with anthracycline toxicity, which is not demonstrated by the standard M mode echocardiogram. Although the overall clinical significance of such diastolic dysfunction is uncertain, some individual abnormalities may have significant management and therapeutic implications.

Adolescent↗
PubMed1994

Decline in incidence of medulloblastoma in children.

BACKGROUND: Medulloblastoma is one of the most common intracranial tumors in children. The perception that the incidence of this tumor has declined is reinforced by a decline in enrollment to international trials for the disease. METHODS: A retrospective population-based study of children younger than 15 years whose brain tumors were reviewed histopathologically was performed in the county of Avon, in the southwest region of England from 1976 to 1991. Then, the incidence of medulloblastoma was studied in the noncontiguous southwest and northern regions of England, with a combined childhood population base of 20.0 million child years for the period 1976-1991. RESULTS: In Avon, 16 children with medulloblastoma presented in the period 1976-1984 and 2 in the period 1985-1991, representing a decrease in incidence from 9.6 per million per year to 1.7 per million per year. The incidence of medulloblastoma in the combined southwest and northern regions showed a significant (P = 0.006) decline from 5.5 per million per year in the period 1976-1984 to 2.8 in the period 1985-1991. Considered individually, the decline in the southwest (from 6.2 per million per year to 2.8 per million per year) was significant but that in the Northern region (from 4.7 to 2.7) was not. CONCLUSIONS: In this report, a decline in the incidence of medulloblastoma was shown. In a recent case control study, a protective effect of maternal folate, iron, and multivitamin supplementation against primitive neuroectodermal tumors, including medulloblastoma was found. The introduction of periconceptional multivitamin supplementation in the 1980s may have caused this significant decline in the incidence of medulloblastoma.

Adolescent↗
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↗
PubMed1994

Childhood malignancies in the south-west region of England, 1976-1985.

The incidence and pattern of childhood cancer in the South-West Region of the United Kingdom was studied in the period 1976-1985 to see if there was any unevenness in distribution. This region consists of five counties with considerable variation in radon exposure and urbanisation. Cases were identified from multiple sources and the basis of the diagnosis reviewed. Internationally accepted diagnostic categories were used. Six hundred seventy-eight cases were found, giving an age standardised incidence rate of 114.2 per million childhood years. The incidence of different cancers by sex was strikingly similar to the Manchester Children's Tumour Registry, from a noncontiguous region, with three exceptions. In the South-West, there was a higher rate of soft tissue sarcoma in boys (P = 0.01) and lower rates of sympathetic nervous system and germ-cell tumours in girls (P = 0.01 and P = 0.04, respectively). There was no significant variation in cancer incidence among the five counties or with time. The incidence rate in counties of high radon exposure was not higher than with low radon exposure. The overall incidence in counties with urban districts was not significantly increased compared to those without, although there was a nonsignificant trend towards a higher incidence of leukaemia (P = 0.08). The incidence and type of childhood cancer are similar to those in a noncontiguous region. Geographical and temporal incidence are remarkably stable. Local environmental variation may not play a major role in the causality of childhood cancer.

Adolescent↗