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Biomedical subjects

M P Coleman

Publications and source records attributed to M P Coleman.

At least 19 recordsLinked to original sources
PubMed2006

Survival trends for small intestinal cancer in England and Wales, 1971-1990: national population-based study.

This population-based study examines prognostic factors and survival trends among adults (15-99 years) diagnosed with small intestinal cancer in England and Wales during 1971-1990 and followed up to 1995. During this period, the 1- and 5-year age-standardised relative survival rates for small intestinal cancers combined were 42% and 23%, respectively. Duodenal tumours, adenocarcinomas, men, patients with advanced age and the most deprived patients had the poorest prognosis. For all small bowel tumours combined, the excess risk of death fell significantly by 6-9% every 4 years over the 20-year period (adjusted excess hazard ratio (EHR) 0.91 at 1 year after diagnosis, 0.94 at 5 years). For duodenal tumours, the EHR fell by about 14% (95% CI 5-22%) every 4 years between 1979 and 1990, and a similar trend for jejunal tumours was of borderline significance. Further population-based investigations linking survival data to individual data on diagnostic methods and types of treatment are needed.

Adolescent↗
PubMed2006

NAD(+) and axon degeneration revisited: Nmnat1 cannot substitute for Wld(S) to delay Wallerian degeneration.

The slow Wallerian degeneration protein (Wld(S)), a fusion protein incorporating full-length nicotinamide mononucleotide adenylyltransferase 1 (Nmnat1), delays axon degeneration caused by injury, toxins and genetic mutation. Nmnat1 overexpression is reported to protect axons in vitro, but its effect in vivo and its potency remain unclear. We generated Nmnat1-overexpressing transgenic mice whose Nmnat activities closely match that of Wld(S) mice. Nmnat1 overexpression in five lines of transgenic mice failed to delay Wallerian degeneration in transected sciatic nerves in contrast to Wld(S) mice where nearly all axons were protected. Transected neurites in Nmnat1 transgenic dorsal root ganglion explant cultures also degenerated rapidly. The delay in vincristine-induced neurite degeneration following lentiviral overexpression of Nmnat1 was significantly less potent than for Wld(S), and lentiviral overexpressed enzyme-dead Wld(S) still displayed residual neurite protection. Thus, Nmnat1 is significantly weaker than Wld(S) at protecting axons against traumatic or toxic injury in vitro, and has no detectable effect in vivo. The full protective effect of Wld(S) requires more N-terminal sequences of the protein.

Animals↗
PubMed2005

The cellular distribution of the Wld s chimeric protein and its constituent proteins in the CNS.

The C57BL/Wld s mouse is a mutant strain of mouse that shows greatly slowed Wallerian degeneration both in the central and peripheral nervous system. Using immunohistochemistry, immunofluorescence and Western blotting, we have investigated the distribution of the chimeric Wld s protein and its different components in neurons of the CNS of Wld s mice and wild-type C57BL/6J mice. The expression of the Wld s protein is restricted to the nucleus in Wld s mice. Wld s was not detected in axons. The Wld s mice express both the normal and chimeric forms of ubiquitination factor E4 (Ube 4b) and nicotinamide mononucleotide adenylyltransferase-1 (Nmnat-1). The normal forms were expressed both in the cytoplasm and the nuclei of neurons in Wld s mice and wild-type mice, and were also present in the axon. The normal form of Ube4b, mono- and poly-ubiquitin and IkappaBalpha, a substrate of Ube4b, were not differentially expressed in Wld s mice compared with wild-type mice. However, the expression of both the normal and mutant forms of Nmnat-1 was higher in the nuclei of Wld s mice compared with wild-type mice. Therefore, axon protection in Wld s mice does not appear to be controlled by expression of Wld s protein in the axons per se and also is unlikely to be related to the different activity of Ube4b either in general ubiquitination or toward this particular substrate. The increased Nmnat-1 activity in the nucleus of Wld s mice compared with wild-type mice seems to be a significant factor in the axon protection. It is not known whether the expression of the Nmnat-1 in the axon is significant.

Animals↗
PubMed2005

Origins of socio-economic inequalities in cancer survival: a review.

BACKGROUND: Cancer survival is known to vary by socio-economic group. A review of studies published by 1995 showed this association to be universal and resilient to the many different ways in which socio-economic status was determined. Differences were most commonly attributed to differences in stage of disease at diagnosis. MATERIALS AND METHODS: A review of research published since 1995 examining the association of cancer survival with socio-economic variables. RESULTS: An association between socio-economic status and cancer survival has continued to be demonstrated in the last decade of research. Stage at diagnosis and differences in treatment have been cited as the most important explanatory factors. Some research has evaluated the psychosocial elements of this association. CONCLUSIONS: Socio-economic differences in cancer survival are now well documented. The explanatory power of stage at diagnosis, although great, should not detract from the evidence of differential treatment between social groups. Neither factor can completely explain the observed socio-economic differences in survival, however, and the importance of differences in tumour and patient factors should now be quantified.

Health Status Indicators↗
PubMed2005

Survival differences between European and US patients with colorectal cancer: role of stage at diagnosis and surgery.

BACKGROUND: Population based colorectal cancer survival among patients diagnosed in 1985-89 was lower in Europe than in the USA (45% v 59% five year relative survival). AIMS: To explain this difference in survival using a new analytic approach for patients diagnosed between 1990 and 1991. SUBJECTS: A total of 2492 European and 11 191 US colorectal adenocarcinoma patients registered by 10 European and nine US cancer registries. METHODS: We obtained clinical information on disease stage, number of lymph nodes examined, and surgical treatment. We analysed three year relative survival, calculating relative excess risks of death (RERs, referent category US patients) adjusted for age, sex, site, surgery, stage, and number of nodes examined, using a new multivariable approach. RESULTS: We found that 85% of European patients and 92% of US patients underwent surgical resection. Three year relative survival was 69% for US patients and 57% for European patients. After adjustment for age, sex, and site, the RER was significantly high in all 10 European populations, ranging from 1.07 (95% confidence interval 0.86-1.32) (Modena, Italy) to 2.22 (1.79-2.76) (Thames, UK). After further adjustment for stage, surgical resection, and number of nodes examined (a determinant of stage), RERs ranged from 0.77 (0.62-0.96) to 1.59 (1.28-1.97). For some European registries the excess risk was small and not statistically significant. CONCLUSIONS: US-Europe survival differences in colorectal cancer are large but seem to be mostly attributable to differences in stage at diagnosis. There are wide variations in diagnostic and surgical practice between Europe and the USA.

Adenocarcinoma↗
PubMed2004

Geographical variation in breast cancer survival rates for women diagnosed in England between 1992 and 1994.

The 5-year relative survival rates of women diagnosed with breast cancer between 1992 and 1994 were compared among the 99 Health Authorities (1999 boundaries) of England. Substantial variation, with evidence of geographical clustering was observed. Part of this variation was explained by differences in deprivation between Health Authorities, in particular by the percentage of class IV and V households. British Journal of Cancer (2004) 90, 2153-2156. doi:10.1038/sj.bjc.6601812 www.bjcancer.com Published online 27 April 2004

Adolescent↗
PubMed2004

Trends and socioeconomic inequalities in cancer survival in England and Wales up to 2001.

We examined national trends and socioeconomic inequalities in cancer survival in England and Wales during the 1990s, using population-based data on 2.2 million patients who were diagnosed with one of the 20 most common cancers between 1986 and 1999 and followed up to 2001. Patients were assigned to one of five deprivation categories (from 'affluent' to 'deprived') using characteristics of their electoral ward of residence at diagnosis. We estimated relative survival up to 5 years after diagnosis, adjusting separately in each deprivation category for background mortality by age, sex and calendar period. We estimated trends in survival and in the difference in survival between deprivation categories ('deprivation gap') over the periods 1986-90, 1991-95 and 1996-99. We used period analysis to examine likely survival rates in the near future. Survival improved for most cancers in both sexes during the 1990s, and appears likely to continue improving for most cancers in the near future. The deprivation gap in survival between rich and poor was wider for patients diagnosed in the late 1990s than in the late 1980s. Increases in cancer survival in England and Wales during the 1990s are shown to be significantly associated with a widening deprivation gap in survival.

England↗
PubMed2004

Colorectal cancer survival trends in Norway 1958-1997.

The purpose of this study was to examine the pattern of survival for colorectal adenocarcinoma (CRC), and to investigate the prognostic factors for the disease. In the analysis, 50993 cases of CRC aged 40-84 years, diagnosed between 1958 and 1997 in Norway, were included. Esteve's relative survival method was used, together with a time trend analysis, conducted by least-squares linear regression. Cox proportional hazards regression analysis was used to examine cause-specific mortality. Five-year relative CRC survival has increased by an estimated 3% per 5-year diagnostic period. In 1958-1962, relative survival was about 40% for both males and females, and increased to 56 and 60%, respectively, in 1993-1997. Rectal cancer had a higher cause-specific mortality (RR 1.26, 95% CI 1.22-1.30) than proximal colon (reference) and distal colon (RR 0.97, 95% CI 0.93-1.00 cancers), while females had a lower cause-specific mortality than males (RR 0.88, 95% CI 0.86-0.90). The increase in the relative survival rate in Norway is probably due to improved treatments and advanced diagnostics. Norway has a higher CRC survival rate than the EUROCARE average.

Adenocarcinoma↗
PubMed2004

Programmed axon death, synaptic dysfunction and the ubiquitin proteasome system.

Axons are essential, vulnerable and often irreplaceable so it is essential to understand how they are lost in neurodegenerative disease. Recent data link the mechanism of injury-induced Wallerian degeneration to that of axon death in CNS and PNS disease. The neuroprotective gene Wld(S) delays Wallerian degeneration, CNS axonal dystrophy, 'dying-back' pathology and to a lesser extent synapse loss, despite the different causes and morphologies of degeneration. These findings validate Wallerian degeneration as a model to understand and prevent mechanisms of axon and synapse loss in neurodegenerative disorders. The existence of a gene that alters Wallerian degeneration suggests it is a regulated program of axon death normally held back by axonal inhibitors, similar in principle to apoptosis. The Wld(S) protein and proteasome inhibitor experiments implicate the ubiquitin proteasome system (UPS) in Wallerian degeneration. However, the site of UPS involvement and the molecular events remain unclear because the UPS is highly compartmentalized in neurons, affecting complex and sometimes conflicting processes in nuclei, axons, growth cones and synapses. Proteasome inhibitors are blunt tools for studying such a complex system and they are also particularly toxic to axons and alter synapse function. In contrast, Wld(S) acts on a specific step, leaving mice healthy with normal development and behavior. This also makes it an attractive drug target. We need to understand which UPS step is blocked in which neuronal compartment, and to define the pathway in order to develop new strategies to block axon pathology.

Animals↗
PubMed2003

Differences in colorectal cancer survival between European and US populations: the importance of sub-site and morphology.

A previous study has shown a lower survival for colorectal cancer in Europe than in the United States of America (USA). It is of interest to examine the extent to which anatomical location and morphological type influence this difference in colorectal cancer survival. We analysed survival for 151,244 European and 53,884 US patients diagnosed with colorectal cancer aged 15-99 years during the period of 1985-1989, obtained from 40 cancer registries that contribute to the EUROCARE study from 17 countries, and nine Surveillance, Epidemiology and End-Results (SEER) registries in the USA. Cases included in the analysis were first primary malignant tumours (ICD-O behaviour code 3 or higher). Relative survival was estimated to correct for competing causes of mortality. The Hakulinen-Tenkanen multiple regression approach was used to examine the prognostic impact of sub-site and ICD-O histology codes. Relative excess risks (RERs) derived from this approach estimate the extent to which the hazard of death differs from that in a reference region after adjustment for mortality in the general population. In order to explore geographical variation, we defined three groups of European registries within which survival rates were known to be broadly similar. The proportion of cases with unspecified sub-site was higher in Europe than the USA (10% versus 2%), but sub-site distributions were broadly similar in the two populations. With the exception of appendix, 5-year survival was 13-22% higher in the USA than in Europe for each anatomical sub-site. The proportion of non-microscopically-verified cases was higher in Europe than the USA (16 versus 3%). Adenocarcinomas arising in a polyp (ICD-O-2 8210, 8261, 8263) were more frequent in the USA than Europe (13 versus 2%). Five-year survival was higher in the USA than Europe for each morphological group, with the exception of non-microscopically-verified cases. When age, gender and sub-site were considered, RERs ranged from 1.52 to 2.40 for the European populations (with the USA as a reference). After inclusion of morphology codes, the range of RERs fell to between 1.28 and 1.86, mainly because of the high frequency of adenocarcinoma in polyps in the USA. This analysis suggests that the large survival advantage for colorectal cancer patients in the USA can only marginally be explained by differences in the distribution of sub-site and morphology. The main explanatory difference is the proportion of adenocarcinoma in polyps.

Adenocarcinoma↗
PubMed2003

The journey towards a cancer diagnosis: the experiences of people with cancer, their family and carers.

This small-scale study aimed to provide an insight into the time between first noticing a symptom, attending a healthcare provider and obtaining a cancer diagnosis. Previous research showed that the pre-diagnostic moments on the illness trajectory were important to people with cancer and could influence levels of satisfaction with subsequent care. This article provides an overview of the qualitative component (phase 2) of a three-pronged study that involved a workshop, a literature review and focus groups and interviews with people affected by cancer. Results highlighted some of the difficulties encountered during the complex journey towards a diagnosis of cancer. These included fear of what might be found, communication of symptoms to healthcare practitioners, the influence of family on decisions to attend a primary care practitioner and the importance of a person's gender on perceptions of health-seeking behaviour. Results presented warrant further investigation and suggest the importance of viewing the 'cancer journey' as including the journey leading up to a diagnosis of cancer.

Adaptation, Psychological↗
PubMed2001

Socioeconomic inequalities in cancer survival in England and Wales.

BACKGROUND: Cancer survival often has been reported as lower for the poor than the rich, but, to the authors' knowledge, systematic national estimates of deprivation gradients in survival over long periods of time have not been available. METHODS: The authors estimated national population-based survival rates for almost 3 million people who were diagnosed with 1 of 58 types of cancers (47 in adults, 11 in children) in England and Wales during the 20-year period 1971-1990 and followed through December 31, 1995. Cancer patients were assigned by their address at diagnosis to 1 of 5 categories (quintiles of the national distribution) of material deprivation by using a standard index derived from census data on unemployment, car ownership, household overcrowding, and social class that was available for all 109,000 census tracts in Great Britain. The authors used relative survival rates: the ratio of observed survival among the cancer patients to the survival that would have been expected if they had had the same background mortality as the general population. Background mortality differed widely among socioeconomic categories, and the authors constructed life tables from raw national mortality data by gender, single year of age, calendar period of death, and socioeconomic category to adjust for it. The authors used variance-weighted least squares regression to estimate both time trends in age standardized survival and socioeconomic gradients in survival. The number of avoidable deaths was estimated from the observed mortality excess compared with the expected mortality in each group of patients. RESULTS: Survival rose steadily for most cancers over 25 years to 1995 in England and Wales, but inequalities in survival between patients living in rich and poor areas were geographically widespread and persistent over this period of time. These patterns existed for 44 of 47 adult cancers examined but not for 11 childhood cancers. These inequalities in survival represented more than 2500 deaths that would have been avoided each year if all cancer patients had had the same chance of surviving up to 5 years after diagnosis as patients in the most affluent group. CONCLUSIONS: The largest national cancer survival study has provided strong evidence of systematic disadvantage in outcome among patients who lived in poorer districts compared with those who lived in wealthier districts.

Adolescent↗
PubMed2001

Coffee consumption and serum aminotransferases in middle-aged Japanese men.

We investigated the relation between coffee drinking and serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) concentrations among 7313 Japanese men receiving a health examination, excluding former alcohol drinkers and men with a history of chronic liver disease. Serum AST > 40 and/or ALT > 40 U/L was defined as liver inflammation. Adjustment was made for alcohol use, smoking, body mass index, serum marker for hepatitis virus infection, and other possible confounders. Adjusted odds ratios of liver inflammation were 1.00 (reference), 0.80, 0.69, and 0.61 for men drinking < 1, 1-2, 3-4, and > or = 5 cups of coffee daily, respectively. Among 6898 men without liver inflammation, serum AST and ALT were inversely associated with coffee consumption, and alcohol-related rise in AST was attenuated with coffee drinking. These findings suggest coffee may have an effect of suppressing the rise of serum aminotransferase, partly by inhibiting the alcohol-related elevation. Studies regarding biological mechanism are warranted.

Alanine Transaminase↗
PubMed2001

Survival from acute non-lymphocytic leukaemia (ANLL) and chronic myeloid leukaemia (CML) in European children since 1978: a population-based study.

We used data supplied by population-based cancer registries, collected and quality controlled using a common protocol, to analyse survival from acute non-lymphocytic leukaemia (ANLL) and chronic myeloid leukaemia (CML) among children in 17 European countries. Variations in survival in relation to age, country, histologic subtype and period of diagnosis (1978--1992) were examined. These are rare malignancies and survival can be studied reliably only by examination of data from a very large population (in this case EUROCARE). 5 years after diagnosis, overall survival was 44% (95% CI 33--55) for CML and 37% (95% CI 32--43) for ANLL. For both types of leukaemia, survival was slightly better for girls and worse in children under 5 years of age. Consistent with clinical literature, the ANLL subtypes with poorer prognosis were monocytic, megakaryocytic and erythroleukaemia. For ANLL, 5-year survival was better in Finland, the UK, The Netherlands and Germany (> or =40%); for CML, 5-year survival was highest in Italy, although the 95% CI were wide. The risk of death from ANLL and CML fell by 7% per year and 5% per year, respectively, after adjustment for age, gender and country. Since these rare childhood malignancies were virtually untreatable until 1970, these are very welcome trends.

Adolescent↗