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APC mutations in familial adenomatous polyposis families in the Northwest of England.

We have investigated a series of FAP patients in the Northwest of England in order to identify and characterise the specific APC mutations. Using SSCP, we found 27 mutations in a total of 50 families investigated. The mutations were predominantly frameshift or nonsense mutations and there were two splice site changes. We have described two patients with severe Gardner's phenotype from different ethnic backgrounds who share the same mutation at codon 1537. Although the frequency of the most common mutation appears low, it is not dissimilar to that reported by other groups.

Adenomatous Polyposis Coli↗

Recent trends in elderly suicide rates in England and Wales.

The proportion of elderly in the population is increasing due to increased life expectancy and falling birth rate, and suicide rates increase with age. This study examined the following in England and Wales: (i) recent trends in the elderly suicide rate; (ii) recent trends in method-specific elderly suicide rate; (iii) the relationship between elderly population size and elderly suicide rate in recent years; and (iv) the sex difference in overall and method-specific elderly suicide rate. Data on the various suicide variables were ascertained from the annually published mortality data for years 1985 to 1996. The main findings of this study were: (i) there is a trend towards decline in the overall pure and combined suicide rates for elderly men and women over the 12 year study period; (ii) the main contributors to this decline are suicides due to poisoning by solid and liquid substances (E950), hanging, strangulation and suffocation (E953), drowning (E954), firearms and explosives (E955), and jumping from high places (E957); (iii) the overall pure and combined suicide rates and that for most categories of suicide was higher in men compared to women; and (iv) suicide rates decreased with an increase in the elderly population size. Suicide rates can decline due to a number of reasons. The challenge now is to ensure further decline in suicide rates to meet the Our Healthier Nations target.

Aged↗

The pattern and structure of one-person households in England and Wales and France.

"This paper examines the increase of one-person households during the 1980s in England and Wales and France set within the broader context of household change in Europe as a whole....One-person households vary geographically by age, with younger one-person households found especially in larger urban areas; older one-person households have a more varied distribution, although rural and traditional retirement areas have particular concentrations. Increases in numbers are a result of both compositional changes in the population (increasing numbers of divorced and never-marrieds as well as increasing numbers of elderly) and also an increasing propensity to live alone, especially among younger age groups."

Age Factors↗

A multi-level perspective on small-area health and mortality: a case study of England and Wales.

"This paper considers morbidity and mortality variations at the small-area level in England and Wales and their relation to socio-economic factors. Separate affluence and deprivation effects on illness and mortality are identified from a single-level analysis, both exceeding the influence of social class, urbanity or ethnicity. A multi-level perspective is then adopted to explore ecological associations operating both at micro-area and higher level spatial scales. Contextual effects (higher level variability in the impacts of ward level variables) are identified in the effects of small area deprivation on mortality and illness, as well as cross-level interactions; thus the impact of small area social structure on health is partly defined by the wider regional and district setting."

Demography↗

Neuroblastoma: changing incidence and survival in young people aged 0-24 years. A report from the North of England Young Persons' Malignant Disease Registry.

BACKGROUND AND PROCEDURE: Population based data for neuroblastoma in children and young adults under 25 years at diagnosis were ascertained from the Northern Region Young Persons' Malignant Disease Registry for the period 1968-1995. Age-standardised incidence rates were calculated (ASR) and changes in incidence and survival were investigated. Over the study period 144 patients were registered, of these 136 were children under 15 years at diagnosis (median age: 2.2 years, ASR: 8.6 cases per million children per year), and 8 were 15-24 years (ASR 0.6). RESULTS AND CONCLUSIONS: Incidence of childhood neuroblastoma in the North of England increased significantly over time; ASRs were 5.8 for 1968-1981 and 9.5 for 1982-1995 (rate ratio: 1.6, 95%; CI 1.2-2.3). The increase in incidence was seen in both infants and older children, and in both low stage and advanced disease. Overall 5 year survival was 15% for 1968-1981 and 40% for 1982-1995 (P < 0.0001). Significant improvements in survival were documented across different stage and age-groups, including those over 1 with stage 4 disease (0% versus 18%, P < 0.0001). Further research is needed to investigate the reasons for the increasing incidence of neuroblastoma.

Adolescent↗

Temporal increases in the incidence of childhood solid tumors seen in Northwest England (1954-1998) are likely to be real.

BACKGROUND: There has been speculation that increasing trends in incidence of childhood central nervous system tumors and infant neuroblastoma in the United States have been due to diagnostic improvements or reporting changes. To investigate whether or not such trends could be explained in this way in the U.K., the authors used population-based data from Northwest England to analyze incidence trends in childhood solid tumors. METHODS: Cases were diagnosed during 1954-1998 and were grouped according to a morphology-based classification scheme. More than 95% of diagnoses were based on special histopathologic review. Tissue sections were retained, and diagnoses were rereviewed to ensure consistency in classification throughout the time period. Age-, gender- and period-specific incidence rates were calculated. Analyses were performed with chi-square tests and Poisson regression. RESULTS: There was an overall increase in the incidence of all childhood solid tumors of 0.9% each year. A temporal increase was found in childhood brain tumors characterized by, in particular, annual increases of 1% in pilocytic astrocytoma, 1% in primitive neuroectodermal tumors, and 2.3% in miscellaneous gliomas. The incidence of germ cell tumors increased at a rate of 2.6% each year. CONCLUSIONS: These increases could not be attributed to changes in diagnostic practice, and it is unlikely that the increases were due to changes in reporting practice. Further, the restriction of the increases to certain groups, with stable rates in others, argued against the changes being artifactual. The authors concluded that the increases in incidence were likely to be real.

Central Nervous System Neoplasms↗

Legal abortion in England and Wales.

Ninety-eight per cent of abortions on British women resident in England or Wales are performed for social reasons. The Abortion Act (1967) insists on the opinion of two doctors but is broadly phrased and, by allowing that abortion can protect mental health, permits abortion when social factors are causing or likely to cause significant stress. The abortion rate has been stable at 11-12 per 1000 women aged 15-44 since 1973, suggesting that factors causing unplanned pregnancy are remaining constant for women in the fertile years and that, overall, the available facilities are adequate. However, only 49% of women obtain a free abortion in the National Health Service (NHS) and there are wide regional variations. Serious delays in the NHS are associated with inadequate access to pregnancy tests, attitudes of medical staff to abortion, and gynaecological units that are fully occupied with other problems. Women can choose to pay for abortions in services run either by charities or by commercial organizations. These services are used electively by a minority of women but most would prefer an NHS abortion if it was easily available. Women who seek help outside the NHS receive prompt and efficient management.

Abortion, Legal↗

Neutropenia and agranulocytosis in England and Wales: incidence and risk factors.

The objectives of this study were to estimate the incidence of idiosyncratic neutropenia and agranulocytosis in England and Wales and to evaluate their risk factors and outcomes. The study was conducted using data from the General Practice Research Database. All cases of idiosyncratic neutropenia or agranulocytosis were identified and the incidence was estimated. This was followed by a nested case-control study, estimating odds ratios with drug exposure from conditional logistic regression. From 1987 to 1999, 3,224 patients with idiosyncratic neutropenia (50 with agranulocytosis) were identified. The incidences of neutropenia and agranulocytosis were estimated to be 120 and 7 cases per million people per year, respectively. The adjusted odds ratios for neutropenia were 34.7 (95% confidence interval 12.0-99.7) for current users of thyroid inhibitors, 9.5 (4.4-20.8) for users of disease-modifying antirheumatic drugs, and 7.6 (4.9-11.9) for users of aminosalicylates. Other drugs with statistically significantly increased risks of neutropenia included antibacterial drugs, non-opioid analgesics, NSAIDs, antidepressants, ulcer-healing drugs, and anti-epileptics. The increase in risk of neutropenia predominantly occurred during the first months of treatment. For most drugs investigated in this study, there was no relationship to daily dose. The excess 1-year mortality was low among neutropenia and agranulocytosis cases and mostly explained by the underlying disease state. In conclusion, the highest risks of neutropenia were generally found in patients starting treatment. The excess 1-year mortality was low among neutropenia and agranulocytosis cases and can be mostly explained by the underlying disease state.

Adolescent↗

Documentary and artistic evidence for conjoined twins from sixteenth century England.

Our knowledge of disease in earlier Britain is largely based on the study of skeletal remains. However, a series of sixteenth century illustrative ballads provides the first proof for conjoined twins from late medieval England. The dearth of archaeological cases may be due to lack of definite skeletal changes or as a result of the remains being denied burial within consecrated ground. Other cases may exist, but documentary evidence is biased to the later medieval period, when such birth defects were recorded solely as a warning against immorality. The famous Biddenden Maids, no doubt, are remembered because of their association with a bequest of land and distribution to the poor.

England↗

Integration of new genetic diseases into statewide newborn screening: New England experience.

Using a data set of newborn screening specimens tested by the New England Newborn Screening Program (NENSP) between January 1999 and February 2003, we analyzed the number of infants with positive newborn screening results and determined how many positive screening results were due to a recent multiplex expansion of services in some of the states. We found that for the subset of the 4-year cohort for which there was a 233% increase in the number of disorders screened (from 9 to 30 disorders), there was a 31% increase in the number of affected infants identified by the screen. We project that if all states in the program expanded their services and if the incidence of disorders is similar across states, there would be an observed 45% increase in the number of infants detected by the screen and a 43% increase in the number of infants for whom the screening algorithm would require some contact with the infants' health care provider. Furthermore, of those requiring contact, we project a 300% increase in the number of screened-positive infants who would be referred to tertiary care centers for a diagnostic evaluation. Increased contact with the medical community from additions to newborn screening as demonstrated in this report emphasizes the need for an approach in which the newborn screening program assures coordinated communications between birth units, laboratory, primary health care providers, and specialists.

Child Health Services↗

Impact of industrialization: comparative study of child health in four sites from medieval and postmedieval England (A.D. 850-1859).

The morbidity and mortality profiles of 831 non-adult skeletons from four contrasting sites in medieval and postmedieval England were compared to assess whether urbanization and later industrialization, had a detrimental effect on the health of the inhabitants. Failure in the population's ability to adapt to these environments should be evident in the higher rates of mortality, retarded growth, higher levels of stress, and a greater prevalence of metabolic and infectious disease in the urban groups. Non-adult skeletons were examined from Raunds Furnells in Northamptonshire, from St. Helen-on-the-Walls and Wharram Percy in Yorkshire, and from Christ Church Spitalfields in London. Results showed that a greater number of older children were being buried at the later medieval sites and that the skeletal growth profiles of the medieval urban and rural children did not differ significantly. A comparison of the growth profiles of St. Helen-on-the-Walls (urban) and Spitalfields (industrial) showed that the Spitalfields children were up to 3 cm shorter than their later medieval counterparts. At Spitalfields, cribra orbitalia and enamel hypoplasias occurred during the first 6 months of life, and 54% of the non-adults had evidence of metabolic disease. It is argued that differences in the morbidity and mortality of non-adults from urban and rural environments did exist in the past, but that it was industrialization that had the greatest impact on child health. Environmental conditions, urban employment, socioeconomic status, and changes in weaning ages and infant feeding practices contributed to differences in health in rural, urban, and industrial environments.

Adolescent↗

Paleopathological and biomolecular study of tuberculosis in a medieval skeletal collection from England.

Nine human skeletons of medieval date from a rural English burial site show signs of skeletal tuberculosis. They were subject to polymerase chain reaction (PCR) assays aimed at detecting traces of DNA from infecting mycobacteria, with the purpose both of confirming the paleopathological diagnosis of tuberculosis and determining in individual cases whether disease was due to M. tuberculosis or M. bovis. In all nine cases, evidence for M. tuberculosis complex DNA was found, and in all instances it appeared that disease was due to M. tuberculosis rather than M. bovis. The significance of the findings for understanding tuberculous infection in rural agrarian communities in medieval England is discussed.

Adult↗

Patterns of anemia and infection from medieval York, England.

An assessment of the presence and patterns of porotic hyperostosis and periosteal reactions in the skeletal population (n = 1,014) from St. Helen-on-the-Walls, York, are used to examine health and disease in urban medieval England. The analyses of these two lesions indicate that 58% of the population display evidence of porotic hyperostosis and that 21.5% of the population display periosteal reactions. Through differential diagnosis it is asserted that porotic hyperostosis is associated with iron-deficiency anemia, and that periosteal reactions may be the result of endemic treponematosis and/or non-specific infection, including parasitic infestation. An association between the presence of remodeled lesions and adulthood is noticeable for both porotic hyperostosis and periosteal reactions, as is a pattern of increased average age at death for those displaying both conditions.

Adult↗

Continuity or colonization in Anglo-Saxon England? Isotope evidence for mobility, subsistence practice, and status at West Heslerton.

The adventus Saxonum is a crucial event in English protohistory. Scholars from a range of disciplines dispute the scale and demographic profile of the purported colonizing population. The 5th-7th century burial ground at West Heslerton, North Yorkshire, is one of the few Anglian cemeteries where an associated settlement site has been identified and subjected to extensive multidisciplinary postexcavation study. Skeletal and grave good evidence has been used to indicate the presence of Scandinavian settlers. A small, preliminary study using lead and strontium isotope analysis of tooth enamel, mineralized in early childhood, from Neolithic/Early Bronze Age (n = 8), Iron Age (n = 2), and Early Anglo-Saxon (n = 32) skeletons, was carried out to directly investigate this hypothesis. Results suggest that lead provides dissimilar types of information in different time periods. In post-Roman England, it appears to reflect the level of exposure to circulated anthropogenic rather than natural geological lead, thus being a cultural rather than geographical marker. Consequently, only strontium provides mobility evidence among the Anglian population, whereas both isotope systems do so in pre-Roman periods. Strontium data imply the presence of two groups: one of "local" and one of "nonlocal" origin, but more work is required to define the limits of local variation and identify immigrants with confidence. Correlations with traditional archaeological evidence are inconclusive. While the majority of juveniles and prehistoric individuals fall within the "local" group, both groups contain juveniles, and adults of both sexes. There is thus no clear support for the exclusively male, military-elite invasion model at this site.

Dental Enamel↗

Age-related cortical bone loss in women from a 3rd-4th century AD population from England.

Age-dependent cortical bone loss in adult females from a skeletal assemblage from 3rd-4th century AD England was studied using metacarpal radiogrammetry. Results showed reduced peak cortical bone thickness compared with modern subjects, and the magnitude of cortical bone loss in older females compared with their younger counterparts was greater than that documented for a modern reference population. An elevated prevalence of fractures classically associated with osteoporosis was also observed in the over-50-year cohort. The severity of osteoporosis in this group is difficult to explain in terms of extraneous factors relating to 3rd-4th century lifestyles. Given the important genetic component in osteoporosis, the results may indicate some inherent susceptibility in this particular population to the disease, and ways in which this possibility might be further explored are suggested.

Age Factors↗

An investigation of skeletal indicators of vitamin D deficiency in adults: effective markers for interpreting past living conditions and pollution levels in 18th and 19th century Birmingham, England.

Vitamin D deficiency in adults is referred to as osteomalacia, and this condition has multiple causes related to factors such as environment, living conditions and cultural practices. Therefore, understanding the types and range of expression of osteomalacia in archaeological bone, using a number of investigative techniques, will have significant implications for interpretations made about past communities. This study aimed to understand the expression of vitamin D deficiency in the skeletons of adults through detailed analysis of human bone from the late 18(th) and 19(th) century churchyard of St. Martin's, Birmingham, England, at a gross, radiological and histological level. The collection from St. Martin's is unusual for the period as this central burial ground in Birmingham was used by a wide cross section of society rather than a narrow socio-economic group as at other sites of this date. Macroscopic and radiological analysis of 291 adults identified seven individuals with osteomalacia, and histological analysis using back-scattered scanning electron microscopy confirmed the findings. Detailed description of the range of pathological alterations observed in the archaeological skeletons are presented, and possible interpretations of the patterns seen considered. The results of this investigation will enable clear diagnosis and interpretation of this vitamin D deficiency disease, an important socio-economic indicator, to take place in the future.

Adolescent↗

New England Medical Center Posterior Circulation registry.

Among 407 New England Medical Center Posterior Circulation registry patients, 59% had strokes without transient ischemic attacks (TIAs), 24% had TIAs then strokes, and 16% had only TIAs. Embolism was the commonest stroke mechanism (40% of patients including 24% cardiac origin, 14% intraarterial, 2% cardiac and arterial sources). In 32% large artery occlusive lesions caused hemodynamic brain ischemia. Infarcts most often included the distal posterior circulation territory (rostral brainstem, superior cerebellum and occipital and temporal lobes); the proximal (medulla and posterior inferior cerebellum) and middle (pons and anterior inferior cerebellum) territories were equally involved. Severe occlusive lesions (>50% stenosis) involved more than one large artery in 148 patients; 134 had one artery site involved unilaterally or bilaterally. The commonest occlusive sites were: extracranial vertebral artery (52 patients, 15 bilateral) intracranial vertebral artery (40 patients, 12 bilateral), basilar artery (46 patients). Intraarterial embolism was the commonest mechanism of brain infarction in patients with vertebral artery occlusive disease. Thirty-day mortality was 3.6%. Embolic mechanism, distal territory location, and basilar artery occlusive disease carried the poorest prognosis. The best outcome was in patients who had multiple arterial occlusive sites; they had position-sensitive TIAs during months to years.

Academic Medical Centers↗