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R A Cartwright

Publications and source records attributed to R A Cartwright.

At least 37 records · Page 2Linked to original sources
PubMed1999

Space-time clustering of acute lymphoblastic leukaemia in parts of the U.K. (1984-1993).

Age-related differences in the incidence and immunological subtypes of acute lymphoblastic leukaemia (ALL) suggest that it may be composed of more than one disease entity, each with different aetiologies. Childhood leukaemia (of which the majority of cases are ALL) has been suspected of having an infectious aetiology, but few studies have systematically examined ALL for clustering by age group. The aim of this study was to examine ALL for evidence of space-time clustering of date and place of diagnosis by age group. Knox space-time analysis was carried out separately for three different age groups: childhood (0-14 years), young adult (15-34 years) and older adults (35-79 years). Data on 968 cases of ALL aged 0-79 years, arising during 1984-1993 in the areas covered by a specialist population based register of leukaemias and lymphomas in parts of the U.K., were used in the analysis. Space-time clustering of diagnoses was limited to children aged 0-14 years. It was more prominent in those diagnosed in the period 1984-1988, than in those diagnosed in 1989-1993. The clustering may indicate an infectious aetiology for childhood ALL, or could be the result of episodic exposures to some environmental hazard.

Adolescent↗
PubMed1999

Leukemias and lymphomas: time trends in the UK, 1984-93.

OBJECTIVE: To investigate recent time trends of some selected and common neoplasms of the blood and lymphatic tissues. METHODS: A specialist population-based register of hematological and related neoplasms was set up in parts of the UK in 1984. Secular changes over the first 10 years were investigated using log-linear Poisson modeling. The results are presented in tabular and graphical form. RESULTS: The analyses of 26,899 cases revealed a decline in incidence of acute myeloid leukaemia (AML), the myeloproliferative disorders (MPD) including chronic myeloid leukaemia (CML) and, in males only, Hodgkin's disease (HD). No secular trends for acute lymphoblastic leukaemia (ALL) were observed at any age. A marked increase in incidence in non-Hodgkin's disease (NHL) and the pre-leukemia group of myeloid dysplasias (MDS) was found. CONCLUSIONS: The rise in MDS and decline in AML and related conditions are most likely to reflect diagnostic changes. Changes in NHL may reflect, in part, a similar phenomena, but an underlying upward trend cannot be excluded. The decline in HD is in one gender only and the significance of this remains to be investigated.

Adolescent↗
PubMed1999

Patterns of care and survival for adolescents and young adults with acute leukaemia--a population-based study.

We report a population-based study of patterns of care and survival for people with acute leukaemia diagnosed at age 15-29 years during 1984-94 in regions of England and Wales covered by specialist leukaemia registries. There were 879 patients: 417 with acute lymphoblastic leukaemia (ALL) and 462 with acute myeloid leukaemia (AML). For ALL, actuarial survival rates were 43% at 5 years after diagnosis and 37% at 10 years. Survival improved significantly between 1984-88 and 1989-94 for those aged 15-19 at diagnosis. Patients entered in national clinical trials and those not entered had similar survival rates. Survival rates were similar at teaching and non-teaching hospitals and at hospitals treating different numbers of study patients per year. For AML, survival rates were 42% at 5 years after diagnosis and 39% at 10 years. Survival improved significantly between 1984-88 and 1989-94. Patients entered in the Medical Research Council AML10 trial had a higher survival rate than those who were in the earlier AML9 trial. Survival did not vary with category of hospital. We conclude that survival has improved for adolescents and young adults with acute leukaemia but that there is at present no evidence that centralized treatment results in a survival benefit for patients in this age group.

Adolescent↗
PubMed1999

Descriptive epidemiology of gastrointestinal non-Hodgkin's lymphoma in a population-based registry.

The incidence of non-Hodgkin's lymphoma (NHL), particularly at certain extranodal sites, has been demonstrated to be rising, at least in the USA, more than for any other malignancy. One of the major sites of extranodal NHL is the gastrointestinal tract, though little is known of its epidemiological characteristics. Over an 8-year period (1986 to 1993) 1069 primary gastrointestinal NHL cases were reported to the Leukaemia Research Fund Data Collection Survey which covers many parts of England and Wales. Age-standardized incidence rates of gastrointestinal NHL at all sites (0.58/10(5) per year), gastric (0.24/10(5) per year), small bowel (0.17/10(5) per year) and large bowel (0.06/1(5) per year) confirmed that the UK has the lowest rates of gastrointestinal NHL in Europe. An excess of males was observed at all ages and for all sites. Time-trend analyses showed annual increases in incidence rates for gastric (6.3%) and small bowel (5.9%) NHL although a concomitant decrease in gastrointestinal NHL of unknown site suggested that at least part of these increases had resulted from more accurate diagnoses. Overall, the incidence of gastrointestinal NHL significantly increased by 2.7% per annum and was limited to the population aged over 50 years in this series.

Adolescent↗
PubMed1999

Space-time clustering of Hodgkin's Disease in parts of the UK, 1984-1993.

The object of this study was to examine cases of Hodgkin's Disease (HD) for evidence of space-time clustering of onsets by age group, sex and disease subtype. Data comprised 2024 cases of HD aged 0-79 years arising throughout the period 1984 to 1993 in the areas covered by a specialist population based register of leukaemias and lymphomas. Knox space-time analysis was used separately for 3 different age groups: childhood (0-14 years), young adult (15-34 years) and older adults (35-79 years); for adult cases separate analysis was carried out by sex and for the nodular and non-nodular sclerosing subtypes. Results showed that space-time clustering of onsets was limited to the nodular sclerosing cases. It was more prominent in young adult nodular sclerosing cases aged 15-34 years (particularly females) diagnosed in the period 1984-88, than in those diagnosed in 1989-93. We conclude that clustering may provide further evidence that an infectious process is involved in the aetiology of young adult nodular sclerosing cases of HD.

Adolescent↗
PubMed1998

Epidemiology of childhood brain tumours in Yorkshire, UK, 1974-95: geographical distribution and changing patterns of occurrence.

From a high-quality population-based register of children with cancer, 455 cases diagnosed with central nervous system (CNS) tumours were analysed to examine patterns of occurrence and geographical distribution. There was a significant increase of 1.8% (95% CI 0.5-3.1, P < 0.01) in average annual incidence for all CNS tumours, mainly accounted for by a 3.1% rise (95% CI 0.1-6.1, P < 0.05) in primitive neuroectodermal tumours (PNETs) over the 22-year period 1974-95. These increases were not explained by an increase in the proportion of histologically verified tumours. In the most recent time period (1986-95), astrocytomas occurred more commonly than previously in 0 to 4-year olds. Geographical differences in incidence were evident at a large scale, between counties, for all tumours and astrocytomas, with lower rates in the most urbanized areas. At the level of census district and electoral wards, no association between incidence of CNS tumours and socioeconomic group, person-based population density or ethnicity was observed using Poisson regression modelling. Based on small-scale census geography, the patterns of distribution of CNS tumours do not suggest strong associations with geographical determinants of risk. This study finds a rising incidence of all CNS tumours and particularly primitive neuroectodermal tumours and shows that astrocytomas appear to be occurring at a younger age, most probably because of improved diagnosis with non-invasive technology.

Adolescent↗
PubMed1998

Mortality and cancer incidence in acromegaly: a retrospective cohort study. United Kingdom Acromegaly Study Group.

Patients with acromegaly have a reduced life expectancy, with the accepted causes for premature death being vascular and respiratory disease. Increased mortality from malignant disease has also been reported. We, therefore, performed a multicenter retrospective cohort study of 1362 patients with acromegaly and investigated the relationships of mortality and cancer incidence with GH levels, duration of disease, and age at diagnosis. The overall cancer incidence rate [standardized incidence ratio, 0.76; 95% confidence interval (CI), 0.60-0.95] was lower than that in the general population of the United Kingdom, and there was no significant increase in site-specific cancer incidence rates. The overall cancer mortality rate was not increased, but the colon cancer mortality rate (standardized mortality ratio, 2.47; 95% CI, 1.31-4.22) was higher than expected. Mortality rates due to colon cancer, all malignant disease, cardiovascular disease and overall mortality were increased with higher posttreatment GH levels (P for trends, <0.02, <0.05, <0.02, and <0.0001). The overall mortality rate in patients with acromegaly with posttreatment GH levels less than 2.5 ng/mL (5 mU/L) was comparable to that in the general population of the United Kingdom (standardized mortality ratio, 1.10; 95% CI, 0.89-1.35). We conclude that high posttreatment GH levels are associated with an increased overall mortality rate and increased mortality rates due to colon cancer, cardiovascular disease, and all malignant disease. Posttreatment GH levels less than 2.5 ng/mL (5 mU/L) result in an overall mortality rate similar to that in the general population.

Acromegaly↗
PubMed1997

Determination of HLA-A*02 antigen status in Hodgkin's disease and analysis of an HLA-A*02-restricted epitope of the Epstein-Barr virus LMP-2 protein.

There is good evidence for an association between Epstein-Barr virus (EBV) and Hodgkin's disease (HD). In approximately one-third of cases, the EBV genome is detectable in Reed-Sternberg (RS) cells and there is expression of the viral nuclear antigen EBNA-1 and the latent membrane protein LMP-1. Expression of LMP-2 has been demonstrated at the mRNA level, and it is presumed that the protein is expressed alongside LMP-1. The LMP-2 protein is known to contain an epitope presented to cytotoxic T-cells which is restricted through the HLA class I antigen A*0201 in healthy seropositive individuals. Since most HLA-A*02-positive Caucasians are HLA-A*0201-positive, it was hypothesized that HLA-A*02-positive individuals would be under-represented among Caucasians with EBV-associated HD. HLA-A*02 status was determined, using flow cytometry and/or the polymerase chain reaction, for 276 individuals including 176 cases of HD. There was no significant difference between the frequency of HLA-A*02 positivity in HD cases and controls, and between EBV-associated and non-associated cases of HD. The A*02 alleles of 14 cases of EBV-associated HD were further subtyped using nested PCR; all except one case were found to be A*0201-positive. We therefore investigated whether there was any evidence for mutation of the epitope representing amino acids 426-434 of LMP-2a which is restricted through HLA-A*0201. In 10/11 cases the nucleotide sequence encoding this epitope was identical to the published sequence; in the remaining case there was a mutation which would not be expected to alter the conformation of the epitope. Overall, our data suggest that other mechanisms of immune escape must be operative in EBV-associated HD.

Adolescent↗
PubMed1997

Age and sex distributions of hematological malignancies in the U.K.

This paper reports on an analysis of nearly 27,000 hematological malignancies diagnosed in the U.K. in the 10-year period 1984 to 1993. The unique observations provided in this analysis are the similarity of the sex-specific curves by age for acute myeloid leukemia, myelodysplasia types, polycythemia rubra vera, and myelofibrosis (or myelosclerosis). The unusual age-sex-specific distribution of essential thrombocythemia, suggesting a unique epidemiology, has never been reported before. The unusual female excess of the nodular sclerosing adolescent peak in Hodgkin's disease and its rapid fall with time is potentially of great importance. An even younger childhood peak of acute lymphoblastic leukemia is presented. Overall these data represent the most reliable available in the U.K., being population based, specially collected and will form the basis of considerable further investigations.

Acute Disease↗
PubMed1997

A comparison of three methods of analysis for age-period-cohort models with application to incidence data on non-Hodgkin's lymphoma.

BACKGROUND: Various methods of analysis have been used to study age-period-cohort models. The main aim of this paper is to illustrate and compare three such methods. Those of Clayton and Schifflers, Robertson and Boyle, and De Carli and La Vecchia. The main differences between these methods lie in their approach to distinguish between linear-period and linear-cohort effects. Clayton and Schifflers do not attempt to solve this identification problem, whereas Robertson and Boyle, and De Carli and La Vecchia attempt to tackle this question. METHODS: In order to study the assumptions and problems of these methods, we analysed data from 2678 subjects aged 30-84 in Yorkshire, UK, who were diagnosed with non-Hodgkin's lymphoma (NHL) during the period 1978-1991. Loglinear Poisson models were used to examine the effects of age, period and cohort. RESULTS: All three methods of analysis agree that, after stratification for sex and county, the age-standardized rate has been increasing at about 5% per year. The Robertson-Boyle method differed from the Clayton-Schifflers method in showing a significant non-linear cohort effect, and a significant county-cohort interaction. The method of De Carli-La Vecchia agreed more closely with Clayton-Schifflers than with Robertson-Boyle. CONCLUSIONS: The linear increase in incidence would lead to a doubling of the number of cases within 15 years. There is controversy over whether the identification problem can be solved and should be solved. Many authors would not rely on the results of the methods of Robertson and Boyle, or De Carli and La Vacchia.

Adult↗
PubMed1997

Small area variation in the incidence of childhood insulin-dependent diabetes mellitus in Yorkshire, UK: links with overcrowding and population density.

BACKGROUND: The incidence of insulin-dependent diabetes mellitus (IDDM) incidence varies between and within countries. The origins of this variation are disputed, but they involve both genetic and non-genetic influences. To explore the role of environmental factors in the aetiology of IDDM we have examined the incidence in small geographical areas and related it to variables derived from national censuses. METHODS: This is an ecological analysis of incidence data from a register of children with IDDM covering the counties of West Yorkshire, North Yorkshire and Humberside in the north of England. All children aged < or = 16, diagnosed with IDDM between 1978 and 1990 were eligible for inclusion. Spatial variation in incidence between electoral wards was investigated using Poisson regression, in relation to socioeconomic status, population density, urban-rural status and measures of geographical isolation. Ward child populations varied in size from 84 to 7197 (mean = 1545). RESULTS: Rates were significantly lower in wards of high population density and with many overcrowded houses. The rate ratio for areas in the upper half of the childhood density distribution was 0.88 (95% confidence interval (CI): 0.78-0.99) and for the two upper tertiles of household overcrowding the rate ratios were 0.84 (95% CI: 0.74-0.95) and 0.68 (95% CI: 0.58-0.79) respectively. CONCLUSIONS: The incidence of childhood IDDM was associated with environmental factors including population density and overcrowded homes. A possible inference from these data is that patterns of infection are involved in the occurrence of IDDM. Analytical epidemiological studies will be needed to investigate these ideas further.

Adolescent↗
PubMed1997

The distribution of leukaemia in association with domestic water quality in south west England.

This study assessed whether there is any variation in the incidence of haematological malignancies between geographical areas of differing water supplies in the South West peninsula of the United Kingdom (1984 to 1988 inclusive). The possibility of correlations existing between variation in water quality and variation in the incidence of haematological malignancies was examined. Haematological incidence data, taken from the Leukaemia Research Fund's Data Collection Study, were mapped into 46 geographical areas of differing water supply. The distribution of the mapped cases was then tested for homogeneity using the Potthoff and Whittinghill (1966) test score. The age-adjusted incidence ratios calculated during the heterogeneity testing were examined for correlations with water quality indicators using correlation and stepwise regression. Significant heterogeneity in the incidence rates among water supply areas was observed for two groups of disease-acute leukaemias and myeloproliferative disorders. Three water quality indicators-pH, nitrate concentration and aluminium concentration-varied considerably over the study period. Significant correlations were observed between the standardized incidence ratios of five disease categories and some water quality indicators, especially aluminium and trihalomethane concentrations. The standardized incidence ratios of some haematological malignancies differed between geographical areas of water supply in South West England, and the evidence suggests that this variation may be associated with variation in water quality indicators. Although this lends support to similar findings in the United States of America, the pattern of correlations are affected by disease latency and statistical methodology.

England↗
PubMed1996

Isolation, car ownership, and small area variation in incidence of acute lymphoblastic leukaemia in children.

To determine whether increased rates of childhood acute lymphoblastic leukaemia (ALL) which had been reported in isolated areas could be attributed to higher proportions of households owning cars, ecological analysis was performed with electoral wards as area units. Previous data were re-analysed using the proportion of households having no car, taken from the 1981 census of England and Wales, as an additional explanatory factor. A specialist registry of haematopoietic malignancies covering one-third of England and Wales (3270 electoral wards) recorded 438 cases of ALL in children diagnosed 1984-89, including 304 in the childhood peak (at ages 1-7 years). Relative risks were derived by Poisson regression of total childhood ALL and at ages 1-7 years for groups of electoral wards classified by isolation and car ownership. Multivariable analyses included adjustment for socio-economic status. No evidence of increased risk of childhood ALL in areas where more households own cars was found. ALL at ages 1-7 years was inversely associated with car ownership (risk in wards with least cars relative to those with most cars = 2.28, 95% CI: 1.12-4.64). The associations with geographic isolation persisted after allowing for car ownership (risks for ALL in young children in isolated relative to built-up areas = 2.19, 95% CI: 1.44-3.33). Levels of car ownership cannot explain the increased rates of childhood ALL which have been observed in isolated areas. No support has been found for a hypothesis relating these excesses to benzene exposure of children transported in cars. The previous explanation for the small area variation of childhood ALL in terms of geographical isolation and interpretation in terms of exposure to common infections continues to be justified.

Adolescent↗
PubMed1996

Increased frequency of HLA-DPB1*0301 in Hodgkin's disease suggests that susceptibility is HVR-sequence and subtype-associated.

Hodgkin's disease (HD) is a complex lymphoma-like disease which occurs as four main subtypes, nodular sclerosing (NS), mixed cellularity (MC), lymphocyte predominant (LP) and lymphocyte depleted (LD). Suggestions from epidemiological studies that HD may represent an unusual response to infection imply that the lack of previous response could be due to genetic factors. Following recent reports suggesting that there is an increased frequency of HLA-DPB1*0301 in Hodgkins disease, we have studied DPB1 in two series of patients using molecular typing methods. One series is a retrospective group of 118 patients over the age of 15 years from a single centre, and the other is a multi-centre prospective group of 45 patients between the age of 16 and 24 years. In both series, the percentage of HD patients with DPB1*0301 is greater than in the controls, confirming that this seems to be an HD-susceptibility allele. However, extension of the analysis in relation to HD subtype shows that the increase in *0301 is present in nodular sclerosing (NS), mixed cellularity (MC) and lymphocyte predominant patients (LP) HD patients, but preliminary evidence suggests an increase in *0401, and possibly *0501 in MC- and LP-HD. The DPB1 hypervariable region (HVR) amino-acid motif Asp55, Glu56 (*0301-like, HVR-C) is increased in NS compared with non-NS (ie MC+LP), whereas the frequency of Ala55, Ala56 (*0401-like) is increased in non-NS compared with NS. Conversely, Asp84, Glu85Ala86(*0301-like, HVR-F) motif is more frequent in NS than non-NS patients, but there is no increase in Gly84, Gly855, Pro86 (*0401-like). These findings suggest that genetic susceptibility in HD may reside at the level of HVR-encoded DPB1 peptide-binding residues, rather than with a specific allele, and that this may in some way influence the HD subtype.

Adolescent↗
PubMed1996

The incidence and distribution of leukaemia and lymphoma within Northern Ireland in the period 1989-1993.

This is the first attempt to systematically record haematological malignancies in Northern Ireland. The methods are identical to a similar effort in other parts of the UK, except that an independent cross check with a cancer registry source was not possible. In addition problems with the census may create differences. Generally, the rates for the leukaemias are slightly lower than in England and Wales, except for acute lymphoblastic leukaemia whilst non-Hodgkin's lymphoma rates are higher. It remains to be seen how stable this situation is as further data are accumulated.

Adolescent↗
PubMed1995

Case clustering, Epstein-Barr virus Reed-Sternberg cell status and herpes virus serology in Hodgkin's disease: results of a case-control study.

The Leukaemia Research Fund Data Collection Study (DCS) is a specialist registry of leukaemias and lymphomas. The present study involves 494 cases of Hodgkin's disease (HD) registered with the DCS between 1985 and 1989. This entire data set has been tested for localised spatial clustering using an established nearest neighbour method with 18% of all cases in young people classified as clustered (P < 0.05). No clustering was found in older cases. Subsamples were selected from the registered cases for a pilot study in which case clustering, herpes virus antibody titres and Epstein-Barr virus (EBV) presence within the Reed-Sternberg (RS) cells (EBV-RS status) were investigated together. Firstly, a case-control study of HD in young people or nodular sclerosing (NS) subtype (39 HD cases and 26 healthy controls) found significant elevation of antibody titres to EBV-viral capsid antigen (VCA), EBV-early antigen (EA) and human herpes virus 6 (HHV-6) in HD cases compared with controls. EBV viral genome was present in 5 cases and 4 of these were in clusters of HD in young people. Elevation of antibody titres to the EBV antigens was not associated with case clustering or EBV-RS status. Antibody titres to HHV-6 differed significantly between EBV-RS+ and EBV-RS- cases (P = 0.04). Geometric mean titres for HHV-6 for EBV-RS+ and EBV-RS- cases were 11.5 and 73.7, respectively, with the former lower than the control value of 20.5. Secondly, a cluster study included all other cases (n = 14) in clusters containing known EBV-RS+ cases. 3 further cases were EBV-RS+ positive but no cluster consisted entirely of positive cases. Overall, 5/16 clustered, 2/12 peripheral and 1/25 random cases in these studies were EBV-RS+ (P = 0.017). The interpretation of these results in terms of shared aetiological exposures of cases within clusters and the roles of EBV and HHV-6 is discussed, and hypotheses for testing in future studies proposed.

Adolescent↗