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Biomedical subjects

A E Evans

Publications and source records attributed to A E Evans.

At least 19 recordsLinked to original sources
PubMed1995

The role of surgery in the management of stage IV neuroblastoma: a single institution study.

The role of surgery in the management of Stage IV neuroblastoma is still far from clear. Seventy-nine patients with this diagnosis presented to the Children's Hospital of Philadelphia during the 10-year period, 1977 to 1986. Four-year survival was 23%. A major resection of the primary tumor was undertaken in 54 patients. The timing of the procedure (at presentation or delayed) had no effect on survival. The patients were divided into three groups based on the extent of surgical resection: Group 1, no surgery or biopsy only (25); Group 2, complete gross resection (34); Group 3, incomplete resection with residual gross disease (20). Four-year survival was 16, 15, and 45%, respectively. The patients were then classified as favorable or unfavorable, on the basis of biological prognostic factors at presentation. When this analysis was combined with the extent of surgery it was discovered that Group 3 contained a higher proportion of favorable patients, accounting for the better survival. Within each group survival correlated with the expected prognosis. The outcome for a patient with Stage IV neuroblastoma depends on the biological characteristics of the tumor, and there is currently no evidence that these can be favorably altered by the timing or extent of surgical resection. Defining the appropriate role of surgery in the management of these patients will require a prospective randomized study which takes into account the inherent biological variability of the disease.

Adolescent↗
PubMed1995

Relationship between dose schedule and charges for treatment on National Wilms' Tumor Study-4. A report from the National Wilms' Tumor Study Group.

National Wilms' Tumor Study-4 was designed to evaluate the efficacy, toxicity, and cost of administration of different regimens for the treatment of Wilms' tumor. The charges for treatment with dactinomycin and doxorubicin administered by two different schedules were calculated using current charges in Buffalo, N.Y. An annual savings of approximately $779,259 could be achieved by the use of the short, pulse-intensive (i.e., single-dose) treatment regimens for all children with Wilms' tumor of stages I-IV/favorable histology. The pulse-intensive administration schedule for the treatment of children with Wilms' tumor permits administration of chemotherapy at a substantially lower total treatment cost.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

Autres pays, autres coeurs? Dietary patterns, risk factors and ischaemic heart disease in Belfast and Toulouse.

The WHO MONICA project monitors trends and determinants in cardiovascular disease to relate classical risk factor changes to trends in incidence rates. The Belfast and Toulouse MONICA centres have also collaborated in dietary studies. Both centres have validated incidence and attack rates for ischaemic heart disease using coronary event registration. These data confirm that the disease in middle-aged men is between three and four times as common in Belfast as in Toulouse. Risk factor surveys show some differences between the centres, but the overall risks assessed by two multiple logistic function scoring systems were identical. A weighed dietary survey revealed no important difference in macronutrient intake, although carbohydrate and saturated fat intake in Belfast was significantly higher. Protein, dietary cholesterol and polyunsaturated fat, particularly linoleic acid intake, was significantly higher in Toulouse, as was consumption of wine, cheese, fruit and vegetables, but not potatoes. The Northern Irish diet is typically Northern European, but although the diet in Toulouse has some features of the Mediterranean diet, it is not appreciably different from that in Belfast in terms of total fat intake. Major differences are present for several food items, and in general these differences add support to the antioxidant hypothesis.

Antioxidants↗
PubMed1995

The effect of diet on lipid, apoprotein and lipoparticle variation in the ECTIM study in Belfast.

The objective of the study was to evaluate the contribution of dietary factors to variation of plasma levels of lipids, apoproteins and lipoparticles in the Northern Ireland population. This study was part of a larger case-control study of the genetic and environmental determinants of myocardial infarction in France and Northern Ireland. A random sample of 175 middle aged men was drawn from the population covered by the Belfast MONICA project register. Habitual diet was assessed by a questionnaire. A blood sample was obtained after an over-night fast for determination of plasma levels of lipids, apoproteins and lipoparticles. All participants had a medical examination and completed a lifestyle questionnaire. In a stepwise regression, after adjusting for co-factors (i) vitamin C and (ii) alcohol consumption were the only nutrients which contributed significantly to the variation in, respectively, (i) Total Cholesterol, LDL Cholesterol and Apolipoprotein B (inverse correlation) and (ii) HDL Cholesterol and LpAI (positive correlation). The amount of variation explained by the final models was modest, ranging from 4% to 15%. In conclusion, in this Northern Ireland population, habitual diet contributes to little of the variation in plasma levels of lipids, apoproteins and lipoparticles.

Adult↗
PubMed1994

Bone marrow transplantation for high risk neuroblastoma at the Children's Hospital of Philadelphia: an update.

A bone marrow transplant (BMT) protocol including surgical excision, local and total body irradiation, and high dose multiagent chemotherapy based on melphalan and bone marrow rescue has been in effect for children with high risk or relapsed neuroblastoma at the Children's Hospital of Philadelphia since 1979. The initial results were reported in 1984 [August et al.: J Clin Oncol 2:609-616, 1984]. This report updates the initial results and those that followed changes in the original conditioning regimen. Forty-two patients were treated between may 1979 and November 1987, and included 27 whose disease had relapsed and 15 who received BMT as part of primary treatment. Allogeneic marrow was given to 12 and autologous marrow to 30; in 7 of these 30, the marrow was purged with monoclonal antibodies and magnetic beads. The 4-year actuarial survival rate is 29%. Ten patients died of early treatment-related complications, 18 died of progressive disease, and 2 died of late complications (1 AIDS and 1 acute myelogenous leukemia). Censoring the two late complications the actuarial 4-year relapse-free survival rate becomes 32%. The longest interval after BMT to relapse was 20 months. There was no significant difference in the survival for patients transplanted following relapse or in first remission. The better survival for patients rescued with autologous marrow (30%) is not statistically significantly different from the result with allogeneic marrow (17%).

Adult↗
PubMed1994

The effect of chemotherapy dose intensity on the hematological toxicity of the treatment for Wilms' tumor. A report from the National Wilms' Tumor Study.

PURPOSE: To determine the relationship between hematological toxicity and actual dose intensity of treatment of patients randomized to therapy during the first 28 months of the National Wilms' Tumor Study-4. METHODS: The mean minimum white blood cell count (WBC), platelet count (PLT), hemoglobin, and absolute neutrophil count (ANC) during the first two courses of chemotherapy and the mean number of days of hospitalization for toxicity were compared between standard and "pulse-intensive" regimens for all randomized patients entered on National Wilms' Tumor Study-4 between August 6, 1986 and December 31, 1988. The mean dose intensity of dactinomycin, vincristine, and doxorubicin received during the first two courses and the entire course of treatment was compared between standard and "pulse-intensive" regimens. RESULTS: The mean minimum WBC, PLT, and ANC were all significantly lower during the first two courses of chemotherapy for stage I patients treated with the standard regimen, compared with the "pulse-intensive" regimen. The mean dose intensity of dactinomycin and doxorubicin was significantly higher for patients treated with the "pulse-intensive" regimens, compared with the appropriate standard regimen. CONCLUSIONS: The "pulse-intensive" administration schedule for the treatment of children with Wilms' tumor permits administration of chemotherapy at a higher dose intensity without an increase in hematological toxicity.

Adolescent↗
PubMed1994

Asthma mortality and death certification in Northern Ireland.

BACKGROUND: Asthma mortality has been rising in many western countries for largely unknown reasons. One cause could be change in certification practice. This study was designed to investigate the accuracy of death certification in Northern Ireland for the years 1981-4 and, in addition, to assess the reliability of trends observed in asthma death registration from 1957 to 1985. METHODS: The following death certificates were obtained for the years 1981-4: those mentioning asthma (all age groups), chronic obstructive airway disease, emphysema, or chronic bronchitis, but only where the decreased was 55 years or less. Information was collected from medical records, questionnaires to the general practitioner, and interviews with a close relative of the decreased. Death as a result of asthma was confirmed or otherwise by a panel and the confirmed deaths were compared with those registered. The numbers of deaths from asthma for the years 1957-85 were obtained from the offices of the Northern Ireland Registrar General. RESULTS: A total of 174 deaths from asthma was identified; 123 (70.7%) had been registered, while the remainder had been coded under another diagnosis. The annual number of confirmed deaths differed little from the figures of the Registrar General. A sharp increase in the annual number of deaths from asthma was observed, beginning in 1977, following a decline in the mid 1970s. CONCLUSIONS: During the years 1981-4 death certification for asthma was found to be inaccurate. The number of false positive registrations was balanced by the number of false negatives, suggesting that the registered totals reflect actual asthma mortality.

Adolescent↗
PubMed1994

Ascorbate and exercise in the Northern Ireland population.

The relationship between physical activity, physical fitness and serum ascorbate was examined in the Northern Ireland Health and Activity Survey. This was a cross sectional population study (n = 1600), using a two stage probability sample, of the population of N. Ireland. Physical activity profile was recorded by computer assisted interview and physical fitness was determined by estimation of VO2 max by extrapolation from submaximal oxygen uptake. Serum ascorbate was measured using a colorimetric reaction of 2,4 dinitrophenylhydrazine with dehydroascorbate. Mean serum ascorbate was greater in females than males (p < 0.001), and was lower in smokers than non-smokers in both males (p = 0.01) and females (p < 0.001). There was no statistically significant relationship between serum ascorbate and age, social class, body mass index, physical activity or physical fitness in males but there was a relationship with age (p < 0.01) and physical fitness (p < 0.05) in females.

Adolescent↗
PubMed1992

The polymorphism ApoB/4311 in patients with myocardial infarction and controls: the ECTIM Study.

The polymorphism affecting codon 4311 of the apolipoprotein B gene (ApoB/4311) was investigated in a large case-control study in two French and one Northern Irish geographically defined populations. Cases were recruited 3 to 9 months after a myocardial infarction (MI) and controls were randomly selected from the population. The polymorphism was assessed using allele-specific oligonucleotides (ASO). The genotype frequencies of the ApoB/4311 polymorphism did not differ in Northern Ireland and France and were in Hardy-Weinberg equilibrium in all groups; strong associations with three other polymorphisms of the ApoB gene (XbaI, EcoRI, VNTR(34 repeats)) were observed and it was possible to identify highly sensitive and specific markers of the ApoB/4311 rare variant. Homozygotes for the ApoB 4311 rare variant were slightly less frequent in cases than in controls: 22 (4.4%) and 35 (6.7%) respectively (population adjusted chi 2 = 3.3 P less than 0.07), especially in Belfast: 6 (3.1%) and 12 (7.6%), respectively (P less than 0.06). Several lipid and lipoprotein parameters were measured. Consistently among control groups, rare homozygotes had lower mean levels of ApoB (P less than 0.02), triglycerides (P less than 0.02), and lipoprotein particles containing ApoE and ApoB (LpE:B; P less than 0.001) and a higher mean level of lipoprotein particles containing ApoAI and not ApoAII (LpAI; P less than 0.02) than heterozygotes and frequent homozygotes combined. The strong association between the ApoB/4311 polymorphism and LpE:B was also observed in patients with MI. When present in the homozygous form, the ApoB/4311 Asn----Ser variant is associated with a lipoprotein profile that is apparently favourable.

Apolipoproteins B↗
PubMed1992

Sites of relapse in patients with neuroblastoma following bone marrow transplantation in relation to preparatory "debulking" treatments.

Forty-one patients with high-risk neuroblastoma were treated between September 1977 and December 1987 at the Children's Hospital of Philadelphia with supralethal chemotherapy and total-body irradiation rescued by bone marrow transplantation. Twenty-six patients were treated following relapse and 15 were newly diagnosed. At the time of evaluation, January 1991, 11 of 41 patients (26.8%) remained in complete remission. Actuarial survival rates of patients transplanted following relapse were 0.35 and 0.31 at 2 and 5 years, respectively, and actuarial disease-free survival rates were 0.38 at 12 months and 0.27 at 24 months. The 2- and 5-year actuarial survival values for the patients with newly diagnosed disease were 0.53 and 0.25, respectively, and the 12- and 24-month disease-free survival rates were 0.47 and 0.27, respectively. There was no significant difference in survival between these groups. Twenty-nine of the 41 patients reviewed were available for analysis of the effect of local treatment. Thirteen had a combination of surgery and radiation (RT), 2 had surgery alone, 9 had RT alone, and in 5 patients no local treatment was given. The local relapse rate was 17%; it was 15% following surgery plus RT and 22% following RT alone. The failure rate combining local and distant relapse is 62% for surgery plus RT and 44% for RT alone. Although a local relapse rate of 17% is imperfect, it is a relatively small contribution to the overall relapse of 62%.

Adrenal Gland Neoplasms↗
PubMed1992

Serum copper and zinc in random samples of the population of Northern Ireland.

Serum copper and zinc concentrations (mumol/L) were measured in nonfasting subjects aged 25-64 y participating in two independent population surveys in Northern Ireland. In 1983-84, copper in 1144 males was 17.2 +/- 3.1 (mean +/- SD) and zinc was 12.1 +/- 1.7 (SD). Copper in 1055 females, neither pregnant nor taking estrogens or progestogens, was 19.0 +/- 3.9 and zinc was 11.6 +/- 1.4. In 1986-87 copper in 1142 males was 17.9 +/- 3.3 and zinc was 13.2 +/- 2.1. Copper in 1034 females was 20.1 +/- 3.9 and zinc was 12.7 +/- 2.0. Zinc but not copper concentrations decreased from early morning to late afternoon; both were unaffected by reported postprandial time. There was a positive relationship between copper and age for both sexes but zinc showed only a slight upward trend with age. A positive relationship between copper and the aggregation of classical risk factors for coronary heart disease was demonstrated.

Adult↗
PubMed1992

The Framingham Type A behaviour pattern and coronary heart disease in three countries: a cross-cultural comparison.

The Framingham Type A behaviour pattern (TABP), a risk factor for cardiovascular disease mortality, was examined in a cross-cultural study involving three countries known to differ in cardiovascular disease mortality, namely Germany, Lithuania and Northern Ireland. The factorial structure of the Framingham TABP scale was strikingly similar in the three countries, with three factors (work pressure, hard driving, and impatience) identified; evidence for the cross-cultural validity of the scale. Scores on all three factors showed considerable variation between the three populations for both men (multivariate P < 0.0001) and women (multivariate P < 0.0001). Of particular note, on the two factors, hard driving and impatience, thought to be core pathogenic elements in the TABP complex, Lithuanian and Northern Irish males and females scored substantially higher than their German counterparts. These cross-cultural variations in levels of risk are discussed in the context of the different ischaemic heart disease mortality rates in the three countries.

Adult↗
PubMed1992

A case-control study of lipoprotein particles in two populations at contrasting risk for coronary heart disease. The ECTIM Study.

The incidence of coronary heart disease (CHD) in middle-aged men is more than three times higher in Northern Ireland than in France. The ECTIM study, which is based on WHO MONICA centers in Belfast (Northern Ireland), Strasbourg (eastern France), Toulouse (southwestern France), and Lille (northern France), has been established to investigate this striking difference. Male patients aged 25-64 years with myocardial infarction (MI) and control subjects sampled from the general population were recruited in the four centers. Hypolipidemic drug treatment was much more frequent in France than in Belfast. "Hypercholesterolemia" defined by the presence of hypolipidemic drug treatment or a low density liproprotein cholesterol level greater than 200 mg/dl was more frequent in cases than in controls in both countries but was similar in both control groups. An in-depth study of lipid variables, including measurements of cholesterol fractions, triglycerides, apolipoproteins (apo), and lipoprotein particles (Lp), was performed in nonhypercholesterolemic subjects. In Northern Ireland and France, patients in comparison with controls had lower levels of high density lipoprotein cholesterol, apo A-I, apo A-II, Lp A-I, and Lp A-II:A-I and higher levels of Lp E:B and Lp(a):B. The levels of triglycerides, very low density lipoprotein cholesterol, apo B, and Lp C-III:B were higher in cases than in controls only in Belfast. In control subjects, the mean levels of cholesterol fractions and apolipoproteins were similar in Northern Ireland and France; however, the level of Lp A-I was lower and the levels of Lp E:B and Lp(a):B were higher in Northern Ireland than in France.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Plasticity of neuroblastoma tumor cells to differentiate along a fetal adrenal ganglionic lineage predicts for improved patient survival.

We have recently presented a model of human adrenal medullary histogenesis that incorporates all neural crest-derived lineages (chromaffin, sustentacular, and ganglionic) known to compose this tissue. To determine if neuroblastomas correspond to the arrested maturation of embryonal adrenal medullary cells, we evaluated the expression of adrenal medullary developmental markers in 81 neuroblastoma tumors. We found that patterns of chromaffin-related gene expression in these tumors correlated exactly with the patterns observed during maturation of adrenal medullary cells (P2 < 10(-5). In a multivariate Cox proportional hazards analysis of developmental marker expression and other well-recognized prognostic variables, evidence of maturation along a fetal ganglionic lineage, as monitored by HNK-1 immunoreactivity (relative risk of 6.42, P2 = 0.0001), and age at diagnosis (relative risk of 5.05, P2 = 0.0042) were independent and significant prognostic indicators of patient survival. These studies demonstrate that neuroblastomas correspond to embryonal adrenal medullary cells arrested at recognizable stages during development, and that evidence of maturation along a fetal ganglionic lineage appears to have major importance in predicting patient survival.

Adrenal Medulla↗
PubMed1991

Models to predict outcome from childhood neuroblastoma: the role of serum ferritin and tumor histology.

We report on the development of three multiple logistic regression models to predict death from childhood neuroblastoma in patients treated without bone marrow transplantation. The models have been developed using a data set of 125 patients for whom age, stage, serum ferritin, and/or histology were available from diagnosis. Seventy-seven patients had all four variables recorded at diagnosis, 34 had age, stage, and serum ferritin, and 14 had age, stage, and histology. Minimum time from diagnosis for all patients was 3 years. The four-variable (full) model showed a predictive value positive rate (or 1 - the false positive rate) of 91.3% and a predictive value negative rate (or 1 - the false negative rate) of 94.4%. Survival curves, based on derived "good" and "poor" prognosis, were constructed for the full model of 77 patients and for the same patients using subset models either without ferritin or without histology. Correcting for prognostic factors noted at diagnosis, no time trend could be identified over the study period. Point estimates for the probability of death in all three models are displayed in graphical form. The results suggest that serum ferritin and tumor histology at diagnosis have independent prognostic significance and that patient outcome in neuroblastoma can be very accurately predicted with a four-variable model. Such information will help sort patients into good and poor prognosis for bone marrow transplant and intensive chemotherapy protocol triage and will help evaluate the efficacy of future therapeutic innovations.

Bone Marrow Transplantation↗