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Biomedical subjects

M Mott

Publications and source records attributed to M Mott.

At least 19 recordsLinked to original sources
PubMed2002

Exposure to power frequency electric fields and the risk of childhood cancer in the UK.

The United Kingdom Childhood Cancer Study, a population-based case-control study covering the whole of Great Britain, incorporated a pilot study measuring electric fields. Measurements were made in the homes of 473 children who were diagnosed with a malignant neoplasm between 1992 and 1996 and who were aged 0-14 at diagnosis, together with 453 controls matched on age, sex and geographical location. Exposure assessments comprised resultant spot measurements in the child's bedroom and the family living-room. Temporal stability of bedroom fields was investigated through continuous logging of the 48-h vertical component at the child's bedside supported by repeat spot measurements. The principal exposure metric used was the mean of the pillow and bed centre measurements. For the 273 cases and 276 controls with fully validated measures, comparing those with a measured electric field exposure >/=20 V m(-1) to those in a reference category of exposure <10 V m(-1), odds ratios of 1.31 (95% confidence interval 0.68-2.54) for acute lymphoblastic leukaemia, 1.32 (95% confidence interval 0.73-2.39) for total leukaemia, 2.12 (95% confidence interval 0.78-5.78) for central nervous system cancers and 1.26 (95% confidence interval 0.77-2.07) for all malignancies were obtained. When considering the 426 cases and 419 controls with no invalid measures, the corresponding odds ratios were 0.86 (95% confidence interval 0.49-1.51) for acute lymphoblastic leukaemia, 0.93 (95% confidence interval 0.56-1.54) for total leukaemia, 1.43 (95% confidence interval 0.68-3.02) for central nervous system cancers and 0.90 (95% confidence interval 0.59-1.35) for all malignancies. With exposure modelled as a continuous variable, odds ratios for an increase in the principal metric of 10 V m(-1) were close to unity for all disease categories, never differing significantly from one.

Adolescent↗
PubMed2002

Lifestyle behaviours of young adult survivors of childhood cancer.

This cross-sectional study collected baseline data on the health behaviours of a large population of survivors of childhood cancer in the UK, aged 18-30 years, compared with those of sex- and age-matched controls. Data from 178 young adult survivors of childhood cancer, diagnosed and treated at Bristol Children's Hospital, 184 peers from the survivors' GP practices and 67 siblings were collected by postal questionnaire. Conditional logistic regression analysis showed that, for matched sets of survivors and controls, survivors of a variety of childhood cancers reported lower levels of alcohol consumption (P=0.005), lower levels of cigarette smoking (P=0.027) and lower levels of recreational drug use (P=0.001) than controls. Analysis of matched sets of survivors and siblings showed similar trends but no significant differences. A health behaviour index for each participant was constructed from the data collected on five key health behaviours which influence future health status. Comparison of the means for each case group showed that survivors of childhood cancer were leading healthier lives than controls or siblings. This finding was expressed most clearly as the difference in the means of the health behaviour index for each case group, derived from five health behaviours (one-way ANOVA, P<0.001).

Adolescent↗
PubMed2000

Zygomycosis in relapsed acute leukaemia.

We would like to report the use of liposomal amphotericin in eradicating mucormycosis in two patients who had relapsed acute leukaemia. The first patient with relapsed acute myeloid leukaemia developed a rapidly expanding solitary necrotic neck lesion associated with opacity of maxilliary sinus at a time when he was profoundly pancytopenic following high dose chemotherapy. The second patient was a 3-year-old boy with pre-B acute lymphoblastic leukaemia who developed a central nervous system relapse whilst on his first line treatment and was treated with more aggressive chemotherapy on the Medical Research Council Relapse Protocol. During a period of profound pancytopenia following re-induction therapy, including high dose steroids and prolonged course of antibiotics for proven septicaemia, he developed periorbital swelling and proptosis and a clinical diagnosis of rhinocerebral mucormycosis was made. Both patients were treated with high doses of liposomal amphotericin (Ambisome Nexstar). The doses were escalated to 10 and 15 mg/kg/day, resulting in successful eradication of the mucormycosis.

Absidia↗
PubMed1999

A transfection compound series based on a versatile Tris linkage.

The family of cationic lipid transfection reagents described here demonstrates a modular design that offers potential for the ready synthesis of a wide variety of molecular variants. The key feature of these new molecules is the use of Tris as a linker for joining the hydrophobic domain to a cationic head group. The molecular design offers the opportunity to conveniently synthesise compounds differing in charge, the number and nature of hydrophobic groups in the hydrophobic domain and the characteristics of the spacer between the cationic and hydrophobic moieties. We show that prototype reagents of this design can deliver reporter genes into cultured cells with efficiencies rivaling those of established cationic lipid transfection reagents. A feature of these reagents is that they are not dependent on formulation with a neutral lipid for activity.

Animals↗
PubMed1998

A limited role for VEEP (vincristine, etoposide, epirubicin, prednisolone) chemotherapy in childhood Hodgkin's disease.

The VEEP regimen (vincristine, etoposide, epirubicin, prednisolone), with or without involved field radiotherapy, has been shown to be an effective treatment in adult Hodgkin's disease. In an attempt to avoid the late sequelae of both alkylating agents and radiotherapy this regimen has been studied in a series of 54 children and young adults. Early analysis suggested that the relapse rate was higher with VEEP than with standard alkylating agent-based regimens. Sufficient follow-up has now been achieved to evaluate the likelihood of sustained remission following second-line treatment and therefore the overall long term survival with this treatment approach. The 5-year Overall Survival (OS) and 5-year Progression Free Survival (PFS) for patients with stage I-III disease was 93% and 82% respectively. However, the 5-year OS and PFS for stage IV patients was only 44% and 50%, respectively. Of 13 patients who were initial treatment failures on VEEP, 7 of whom had advanced disease, only 6 were salvaged with second-line therapy. 8 of 33 who attained a complete response (CR) relapsed and there were 2 relapses in those achieving a partial response (PR) (n = 8). All those relapsing from CR/PR were salvaged by second-line alkylating agent chemotherapy +/- radiotherapy, +/- high dose chemotherapy. In conclusion, patients with stage I-IIIA, non-bulky disease, the moderately high relapse rate did not adversely affect the overall high cure rate, although VEEP failures were subjected to a high total treatment burden. VEEP alone is inadequate in patients with stage IV disease, bulky mediastinal disease in/or those with B symptoms in whom there is a high primary failure rate and relatively poor results with second line therapy.

Adolescent↗
PubMed1998

Phase I study of temozolomide in paediatric patients with advanced cancer. United Kingdom Children's Cancer Study Group.

A phase I study of temozolomide administered orally once a day, on 5 consecutive days, between 500 and 1200 mg m(-2) per 28-day cycle was performed. Children were stratified according to prior craniospinal irradiation or nitrosourea therapy. Sixteen of 20 patients who had not received prior craniospinal irradiation or nitrosourea therapy were evaluable. Myelosuppression was dose limiting, with Common Toxicity Criteria (CTC) grade 4 thrombocytopenia occurring in one of six patients receiving 1000 mg m(-2) per cycle, and two of four patients treated at 1200 mg m(-2) per cycle. Therefore, the maximum-tolerated dose (MTD) was 1000 mg m(-2) per cycle. The MTD was not defined for children with prior craniospinal irradiation because of poor recruitment. Plasma pharmacokinetic analyses showed temozolomide to be rapidly absorbed and eliminated, with linear increases in peak plasma concentrations and systemic exposure with increasing dose. Responses (CR and PR) were seen in two out of five patients with high-grade astrocytomas, and one patient had stable disease. One of ten patients with diffuse intrinsic brain stem glioma achieved a long-term partial response, and a further two patients had stable disease. Therefore, the dose recommended for phase II studies in patients who have not received prior craniospinal irradiation or nitrosoureas is 1000 mg m(-2) per cycle. Further evaluation in diffuse intrinsic brain stem gliomas and other high-grade astrocytomas is warranted.

Adolescent↗
PubMed1995

Neonatal vitamin K administration and in vivo somatic mutation.

The glycophorin A (GPA) mutation assay was used to examine the risk of in vivo somatic mutation in infants following neonatal administration of vitamin K. The assay assesses damage to erythroid stem cells by measuring the frequency of NO and NN variant red cells of MN blood group heterozygotes using FACS analysis. Blood samples were obtained from 178 infants aged between 10 and 183 days. Twenty-six children were excluded from study having received a blood transfusion. Sixty-four of the remaining 152 infants were of the MN phenotype, samples from whom were analysed using the assay system, providing the first data of NO and NN variant frequencies (vfs) in children aged less than 1 year. Twenty of these 64 infants received vitamin K orally (group A), 17 intramuscularly (group B) and 25 intravenously (group C). Results were compared with those from a reference population of children aged 1-15 years. There were no significant differences in NO, NN and total vf between any of groups A, B and C. For all groups both NO and total vf were significantly lower than those for the control population. This result is of some interest and clearly warrants further investigation. NN and total vfs were greater than the 95th percentile for the pooled data from groups A, B and C in three instances, one in each group. It was thus not possible to demonstrate an association between the route of vitamin K administration and an increase in mutation at the GPA locus.

Administration, Oral↗
PubMed1992

Childhood cancer, intramuscular vitamin K, and pethidine given during labour.

OBJECTIVE: To assess unexpected associations between childhood cancer and pethidine given in labour and the neonatal administration of vitamin K that had emerged in a study performed in the 1970 national birth cohort. DESIGN AND SETTING: 195 children with cancer diagnosed in 1971-March 1991 and born in the two major Bristol maternity hospitals in 1965-87 were compared with 558 controls identified from the delivery books for the use of pethidine during labour and administration of vitamin K. MAIN OUTCOME MEASURES: Odds ratios for cancer in the presence of administration of pethidine or of intramuscular vitamin K. Both logistic regression and Mantel-Haenszel techniques were used for statistical analyses. RESULTS: Children of mothers given pethidine in labour were not at increased risk of cancer (odds ratio 1.05, 95% confidence interval 0.7 to 1.5) after allowing for year and hospital of delivery, but there was a significant association (p = 0.002) with intramuscular vitamin K (odds ratio 1.97, 95% confidence interval 1.3 to 3.0) when compared with oral vitamin K or no vitamin K. There was no significantly increased risk for children who had been given oral vitamin K when compared with no vitamin K (odds ratio 1.15, 95% confidence interval 0.5 to 2.7). These results could not be accounted for by other factors associated with administration of intramuscular vitamin K, such as type of delivery or admission to a special care baby unit. CONCLUSIONS: The only two studies so far to have examined the relation between childhood cancer and intramuscular vitamin K have shown similar results, and the relation is biologically plausible. The prophylactic benefits against haemorrhagic disease are unlikely to exceed the potential adverse effects from intramuscular vitamin K. Since oral vitamin K has major benefits but no obvious adverse effects this could be the prophylaxis of choice.

Administration, Oral↗
PubMed1992

'VEEP' in children with Hodgkin's disease--a regimen to decrease late sequelae.

In an attempt to decrease the risk of second malignancies and future infertility in children with Hodgkin's disease (HD) while retaining acceptable remission rates, an anthracycline based regimen containing no alkylating agent has been devised. VEEP contains vincristine, epirubicin, etoposide and prednisolone given at 3 weekly intervals. Forty-four patients, aged 2-15 years, have been treated: ten relapsed patients and 34 previously untreated with chemotherapy (including three relapsed stage I treated initially with radiotherapy). The median follow up for all patients is 25 months (range 6-52 months). The response rate in previously treated patients was 80% (95% CI 44-97%) and five remain alive in remission. The response rate in untreated patients was 88% (95% CI 72-97%) with 62% CR + CR(u) (uncertain/unconfirmed) (95% CI 44-77%). Of four patients who had a final response of CR(u) three have relapsed at 9, 16 and 38 months. Two of the children in CR have relapsed at 6 and 16 months. The relapse free rate at 3 years is 67% (95% CI 17-82%). In this pilot study the event free survival appears somewhat poorer than conventional combinations and further follow up is required to confirm the salvagability of relapsed patients.

Adolescent↗
PubMed1990

'JEB'--a carboplatin based regimen for malignant germ cell tumours in children.

Between February 1986 and July 1988 a total of 21 children aged 1 to 16 years with malignant germ cell tumours (MGCT), 18 with either metastatic disease or unresectable primary tumour, received the JEB regimen - carboplatin dosage calculated from the EDTA glomerular filtration rate (approximately 600 mg m-2), etoposide 120 mg m-2 daily x 3, and bleomycin 15 mg m-2 weekly. Primary sites were: testis (6), ovary (8), sacrococcyx (4), pineal gland (2) and vagina (1). AFP levels were elevated in 19, beta-HCG in 8. Complete marker response was achieved in 19 out of 19 evaluable patients and complete remission of measurable tumour in 16 out of 19, 12 with chemotherapy alone and 4 with the addition of surgery. A reduction in glomerular filtration rate greater than 10% occurred in 3 of 12 evaluable patients; in none greater than 20%. Sequential audiography was normal in 11 out of 12 evaluated. The regimen was myelosuppressive with WHO grade III or IV myelosuppression occurring in 12 patients. Three patients have relapsed; one with a pineal germinoma who relapsed in the abdomen six months after diagnosis, and two with sacrococcygeal teratomas and lung metastases. Two of these remain in second complete remission after further treatment. There was one death from probable bleomycin pulmonary toxicity. We conclude that this regimen is simple to administer and, apart from myelosuppression, it is well tolerated. It appears to have comparable efficacy to cisplatin-based regimens but with much less nephrotoxicity and ototoxicity and avoids the use of alkylating agents and anthracyclines.

Adolescent↗
PubMed1990

Do visual evoked potentials detect neural damage in children treated for cancer?

Abnormal visual evoked potentials (VEPs) have been reported in children treated for acute lymphoblastic leukaemia (ALL), which suggests that VEPs may be useful in screening for toxicity. The authors investigated this by recording flash and pattern VEPs in a control group of 34 siblings of patients, a group of six children studied longitudinally during the early stages of treatment for ALL, and three other follow-up groups. In only three follow-up patients were VEP results outside the normal range and the six ALL patients did not develop new abnormalities during early treatment. Although differences were detected between the groups, there was no evidence of VEPs being a useful means of monitoring the treatment of individual patients.

Adolescent↗
PubMed1988

Combined chemotherapy and surgery for pulmonary metastases from osteogenic sarcoma. Results of 10 years experience.

Twenty-three patients presented with isolated pulmonary metastases from osteogenic sarcoma following primary treatment by amputation or limb salvage, combined with chemotherapy. The metastases were treated by conservative surgical excision combined with chemotherapy; surgical excision was repeated for recurrent pulmonary metastases, provided there were none elsewhere. Six patients are alive and disease-free following their initial surgery. Of the remaining 17, 10 had recurrence confined to the lungs, and 7 developed extra-pulmonary metastases. The 10 with isolated pulmonary metastases all had further thoracotomies but eventually 7 died, as did all those with extra-pulmonary metastases. There were in all 45 operations, with 1 hospital death and 1 serious complication. Actuarial survival at 1, 3, 5 and 7 years was 87%, 45%, 39% and 31%, respectively. In the 10 patients who had recurrence of isolated pulmonary metastases, survival at 1 and 3 years was 70% and 34%.

Adolescent↗
PubMed1988

Expression of the N-myc oncogene in Wilms' tumour and related tissues.

Tissue samples and cell cultures from Wilms' tumour matched histologically normal kidney samples and EBV transformed B cells from the same patients, were analysed to detect changes in the structure and expression of the N-myc oncogene. The levels of expression of HLA class I and hypoxanthine guanine phosphoribosyl transferase were also measured in the various RNA preparations. Related tissue samples, from sources including congenital mesoblastic nephroma, paediatric neuroblastoma and a number of foetal tissues were also tested. Northern blot analysis indicated that the levels of N-myc were higher in Wilms' tumour tissues (with no parallel increase in gene copy number) compared to all other sources of material including foetal kidney. Particularly high levels of expression were observed in a number of the Wilms' tumours, several of which produced metastases. In situ hybridization, using [35S]-labelled RNA probes, confirmed that the high levels of N-myc RNA were present in the blastemal elements in the Wilms' tumour. All the tissue cultures, and tissue samples from other sources, except foetal brain and neuroblastoma, contained uniformly low levels of N-myc RNA.

Child↗
PubMed1978

Prevalence of hepatitis B in a high-risk setting: a serologic study of patients and staff in a pediatric oncology unit.

The prevalence of serologic markers for hepatitis B virus (HBV) among 188 patients and 158 employees in a pediatric oncology unit was evaluated. Evidence of past or present HBV infection was detected in 33 patients (18%) and in 25 employees (16%). The prevalence was higher among patients receiving chemotherapy (19%) than among those not receiving chemotherapy (7%). The prevalence of HBV serologic markers, while much higher than generally found among healthy children in the United States, was low compared to previously reported prevalences in such settings, and may reflect the use in recent years of blood and blood products screened by "third generation" methods (radioimmunoassay and reversed passive hemagglutination) for hepatitis B surface antigen and the use of all volunteer blood donors. This prevalence suggests that perhaps there is less urgent need for the use of hepatitis B immune globulin and hepatitis B vaccine (when it becomes available) in oncology units than had been anticipated from earlier data in oncology units.

Adolescent↗