Search PubMed⌕ Search

Biomedical subjects

M L Willoughby

Publications and source records attributed to M L Willoughby.

At least 19 recordsLinked to original sources
PubMed2001

Maternal folate supplementation in pregnancy and protection against acute lymphoblastic leukaemia in childhood: a case-control study.

BACKGROUND: Acute lymphoblastic leukaemia is the most common childhood cancer in more-developed countries but it has few recognised risk factors or preventive measures. We aimed to determine and assess the risk factors associated with this disease. METHODS: From 1984 to 1992, we investigated known and suspected risk factors for common acute lymphoblastic leukaemia diagnosed in a population-based case-control study of children aged 0-14 years in Western Australia. 83 children in the study group came from the sole referral centre for paediatric cancer in the state and 166 controls matched for age and sex were recruited through a postal survey of people randomly selected from the state electoral roll. We interviewed mothers of 83 study and 166 control children (82% and 74%, respectively, of those eligible). Fathers completed a self-administered questionnaire. FINDINGS: We recorded a protective association between iron or folate supplementation in pregnancy and risk of common acute lymphoblastic leukaemia in the child (odds ratio 0.37 [95% CI 0.21-0.65]; p=0.001). For iron alone, the odds ratio was 0.75 (0.37-1.51); only one mother took folate without iron. Further analyses of folate use with or without iron (0.40; 0.21-0.73) showed that the protective effect varies little by time of first use of supplements or for how long they were taken. The association was not weakened by adjustment for potentially confounding variables. INTERPRETATION: Our results, though unexpected, suggest that folate supplementation in pregnancy reduces the risk of common acute lymphoblastic leukaemia in the child.

Adolescent↗
PubMed1998

Survival after relapse in childhood acute lymphoblastic leukemia: impact of site and time to first relapse--the Children's Cancer Group Experience.

BACKGROUND: Childhood acute lymphoblastic leukemia is the single most common childhood malignancy. Despite substantial improvements in therapy, cases in which relapse occurs are still more common than newly diagnosed cases of many other childhood cancers. The survival of patients who relapse despite improved therapy continues to be of interest. METHODS: One thousand one hundred forty-four relapses and 28 second malignant neoplasms were identified among the 3712 eligible patients enrolled on Children's Cancer Group trials between 1983 and 1989. The details of treatment after relapse were not accessible. Subsequent secondary event free survival and overall survival were examined by the site of and time to initial relapse. A variety of potential prognostic factors were examined employing the log rank statistic and Wilcoxon regression model. RESULTS: Rates of 6-year survival (+/- standard error) after isolated bone marrow, isolated central nervous system (CNS), and isolated testis relapse were 20%+/-2%, 48%+/-4%, and 70%+/-5%, respectively. Rates of survival after isolated bone marrow relapse at 0-17 months, 18-35 months, and after 36 months were 6%+/-2%, 11%+/-2%, and 43%+/-4%, respectively. Rates of survival after isolated CNS relapse at 0-17 months, 18-35 months, and after 36 months were 33%+/-4%, 59%+/-5%, and 72%+/-8%, respectively. Rates of survival after isolated testis relapse at 0-17 months, 18-35 months, and after 36 months were 52%+/-11%, 57%+/-10%, and 81%+/-5%, respectively. Rates of survival after combined bone marrow and CNS or testis relapse at 0-17 months, 18-35 months, and after 36 months were 9%+/-5%, 11%+/-6%, and 49%+/-7%, respectively. CONCLUSIONS: Substantial survival at 6 years is evident among several subsets of this unselected group of heterogeneously treated children, namely, those with isolated or combined bone marrow relapse after 36 months and those with isolated extramedullary relapse at any time. Second malignant neoplasms are rare thus far.

Child↗
PubMed1995

New translocation t(2;13)(p12;q34) and rearrangement of the MLL gene in a childhood leukemia cell line.

Here we report the case of a 7-month-old boy who presented with biphenotypic acute leukemia, but with leukemia cells of B-cell phenotype present at the time of relapse. Two cell lines were derived from bone marrow specimens obtained at relapse, and immunophenotyping and analysis of antigen receptor gene configuration revealed concordance between the patient's leukemic cells and the cell lines. Cell line PER-377 shows a new chromosomal abnormality, t(2;13)(p12;q34), a molecular rearrangement at chromosome band 11q23 in the absence of a cytogenetically detectable abnormality of this band, and deletion of the genes for IGK.

Biomarkers, Tumor↗
PubMed1994

Enhanced MYCN expression and isochromosome 17q in pineoblastoma cell lines.

We have established two cell lines, PER-452 and PER-453, from an 8-month-old girl with an extensive pineoblastoma. Characterization of these lines revealed that the proto-oncogenes MYC and MYCN were not amplified, but both cell lines showed MYCN expression comparable to a cell line with 200-fold MYCN amplification. Both cell lines contained an i(17q). These results support the concept that pineoblastomas belong to a larger group of primitive neuroectodermal tumors of the central nervous system. These two cell lines provide a unique opportunity to investigate the molecular genetic mechanisms underlying these neoplasms further.

Brain Neoplasms↗
PubMed1992

Two malignant peripheral primitive neuroepithelial tumor cell lines established from consecutive samples of one patient: characterization and cytogenetic analysis.

A 6-year-old girl presented with a tumor of the right shoulder involving bone, adjacent soft tissue, and regional lymph nodes. The conventional histologic diagnosis was ambiguous, initially suggesting lymphoma. After relapse on lymphoma therapy, reevaluation with additional multiple diagnostic techniques performed on the biopsy tissue and on two cell lines derived from the biopsies established the diagnosis of a primitive neuroepithelial tumor of bone and soft tissue. This was strongly supported by 1) focal rosette formation by the tumor cells and positive immunostaining for neuron-specific enolase and synaptophysin, with absent staining for leukocyte common antigen; 2) at the ultrastructural level, formation of cellular processes containing microtubules, a paucity of neurosecretory granules, absence of synaptic junctions, formation of long "intermediate" junctions between cells, and, in culture, widespread development of rosettes; 3) marked surface positivity to W 6/32 and negativity to HSAN 1.2 antibodies; and 4) elevated expression of MYC and lack of overexpression of MYCN oncogenes. Numerical and structural abnormalities were present in the karyotype, but the expected t(11;22)(q24;q12) was not present in the tumor-involved marrow or in either of the established tumor cell lines, although there was an interstitial deletion of 11q involving breakpoints in q21 and q23.

Biomarkers, Tumor↗
PubMed1991

Intrathoracic carcinoma in an 11-year-old girl showing a translocation t(15;19).

We report here a rare case of intrathoracic undifferentiated carcinoma in an 11-year-old girl. The biopsy tissue stained with antibodies against cytokeratin and carcino-embryonic antigen. The same staining was obtained using a cell line, PER-403, which was derived from the tumor. DNA from PER-403 cells was tested for the presence of Epstein-Barr virus genes, yielding a negative result. The cytogenetic analysis found a translocation t(15;19) (p12;q13), which has not previously been described in a carcinoma.

Carcinoma↗
PubMed1990

Establishment and characterization of a childhood pre-B acute lymphoblastic leukemia cell line, PER-278, with chromosome translocations t(1;19) and t(1;9).

Cell line PER-278 was established from a bone marrow sample of a 10-year-old boy diagnosed with pre-B acute lymphoblastic leukemia (ALL). PER-278 cells show the pre-B phenotype, express cytoplasmic Ig, and exhibit two translocations: t(1;19)(q23;p13) and t(1;9)(q23;p13). Assessment of the immunoglobulin rearrangements confirmed the clonal origin of cell line PER-278, and comparison with the patients's leukemic cells showed an identical pattern: loci involved at the breakpoint on chromosome 1 code for the oncogene SKI and for the Fc receptor II and on chromosome 19 for the insulin receptor. The t(1;19) may contribute to the malignant transformation in leukemic cells of pre-B phenotype.

Child↗
PubMed1989

Pharmacology studies of 1-beta-D-arabinofuranosylcytosine in pediatric patients with leukemia and lymphoma after a biochemically optimal regimen of loading bolus plus continuous infusion of the drug.

In an attempt to maximize the therapeutic index and to overcome the large variations in 1-beta-D-arabinofuranosylcytosine (ara-C) plasma levels and host toxicities that have been documented with standard HDara-C regimens (3 g/m2 over 3 h every 12 h x 8 or x12 doses), pediatric patients with acute lymphocytic leukemia or lymphoma in relapse were treated with a regimen of loading bolus followed immediately by continuous infusion of ara-C. In addition, patients received a single dose of etoposide (VP-16, 1 g/m2) prior to the ara-C administration. In four patients, total body irradiation was administered as part of a bone marrow transplantation preparative regimen after the ara-C administration. The regimen was designed to attain and maintain plasma steady-state concentrations (Css) of ara-C three to four times the Km2 value of ara-C, which was determined with purified deoxycytidine kinase from the patients' tumor cells prior to treatment. Eight patients age 0.75 to 16 years with relapsed acute lymphocytic leukemia (three patients) or lymphoma (five patients, one with bone marrow involvement), received a test dose of 3 g/m2 ara-C injected over 1 h, and the plasma kinetics were determined. The peak plasma ara-C concentration of ara-C ranged from 57 to 199 microM with an average concentration of 103 +/- 49 microM; the half-lives of distribution (t1/2, alpha) and elimination (t1/2, beta) averaged 17 +/- 7 min and 4.04 +/- 3.1 h, respectively. The mean area under the plasma concentration time curve from 0 to 12 h (AUC0----12 h) of ara-C averaged 386.8 +/- 328.0 microMh (mean, +/- SD, n = 8). The peak concentration of uracil arabinoside averaged 501 +/- 123 microM, and it was eliminated with a t1/2, el of 2.3 +/- 0.6 h. The patients then received an individualized loading bolus (mean = 0.5 g/m2) followed by a continuous infusion regimen of ara-C (mean = 130 mg/m2/h), to achieve a Css in the range of 20 to 35 microM. The obtained plasma Css were similar to the desired ones, averaging in variation 10.7% +/- 8.2%. The percentage of variation of correlation of the AUC following the loading bolus plus the continuous infusion from 12 to 72 h was only 12.4% (mean = 2158 microMh, n = 8), whereas the percentage of variation of correlation of the AUC after the test dose of ara-C in the same patients was 84.8%.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1984

Adjuvant low dose radiation in childhood T cell leukaemia/lymphoma (report from the United Kingdom Childrens' Cancer Study Group--UKCCSG).

From November 1977 to July 1983, 82 children with T leukaemia/lymphoma entered a randomised trial of combination chemotherapy and radiotherapy. Twenty-five were designated T lymphoma and 57 T leukaemia, 28 having greater than 100 x 10(9)1(-1) blasts in peripheral blood at diagnosis. Twenty-seven patients with mediastinal primaries who were treated on the companion non-Hodgkin lymphoma (NHL) trial were comparable in all respects to the T lymphoma patients and the results of treatment were therefore combined and analysed together. Overall 4-year survival (48-53%) and failure-free survival (FFS) (37-40%) were similar in all groups except the 28 with T leukaemia and WCC greater than 100 X 10(9)1(-1) (20% and 13%). There was a significant advantage in FFS for patients randomised to receive low dose mediastinal radiation, and this was most marked in patients with T lymphoma (66% vs 18%, P = 0.006).

Adolescent↗
PubMed1982

Establishment and characterization of human neuroblastoma and ganglioneuroblastoma cell lines.

The establishment in culture and characterization of 4 human neuroblastoma (NB) cell lines and 1 human ganglioneuroblastoma cell line are described. Each cell line fulfilled at least 2 of 4 criteria for malignant or transformed cells: viz., subcultured more than 70 times, high saturation density with absence of contact inhibition, population-doubling time within a range of 10-40 h, and tumour formation in nu/nu mice. Each cell line also fulfilled at least 2 of 3 criteria for neuroblastoma cells: viz., humoral and cell-mediated immune reactivity toward NB-associated cell-surface antigen, intracellular storage and extra-cellular secretion of catecholamines, and characteristic neuroblast and ganglion-cell morphology.

Animals↗
PubMed1982

Rationale behind the periodic health examination in adults.

We have outlined a comprehensive approach to the periodic examination of adults. We do not discuss reasons for excluding specific practices. The approach outlined eliminates many practices that have become part of the "routine examination" and focuses on specific key areas. Our recommendations are practical and somewhat more inclusive than those of the others. We have not addressed mass screening, but have instead defined a periodic health examination applicable to the unique physician-patient relationship.

Adult↗
PubMed1982

Tumor-directed immunity in human neuroblastoma.

Tumor-directed immunity was assessed in 29 patients with neuroblastoma (NB). Cell-mediated and humoral immunity were assessed in vitro using the one-stage direct capillary leukocyte migration inhibition test and the indirect, membrane immunofluorescence test, respectively. Leukocytes from 83% of NB patients, 40% of normal children, and 24% of adults were inhibited by NB-derived materials. NB patients' leukocytes reacted as frequently with materials from allogeneic neuroblastomas as with autologous extracts. Sera from 50% of NB patients, 8% of child controls, and 18% of adult controls reacted with allogeneic tissue cultured neuroblastoma cells. Leukocytes from NB patients, control children, and control adults were inhibited at a similar low frequency by extracts of human melanomas and cancers of cervix, colon, and breast. Sera from NB patients and controls reacted infrequently with cultured melanoma cells.

Antibody Formation↗