Epidemiology of Paget's disease of bone.
Explore the source record for details and available documents.
Age Distribution↗
Biomedical subjects
D Barker
Publications and source records attributed to D Barker.
Germline BRCA1 alterations in a population-based series of ovarian cancer cases.
The objective of this study was to provide more accurate frequency estimates of breast cancer susceptibility gene 1 ( BRCA1 ) germline alterations in the ovarian cancer population. To achieve this, we determined the prevalence of BRCA1 alterations in a population-based series of consecutive ovarian cancer cases. This is the first population-based ovarian cancer study reporting BRCA1 alterations derived from a comprehensive screen of the entire coding region. One hundred and seven ovarian cancer cases were analyzed for BRCA1 alterations using the RNase mismatch cleavage assay followed by direct sequencing. Two truncating mutations, 962del4 and 3600del11, were identified. Both patients had a family history of breast or ovarian cancer. Several novel as well as previously reported uncharacterized variants were also identified, some of which were associated with a family history of cancer. The frequency distribution of common polymorphisms was determined in the 91 Caucasian cancer cases in this series and 24 sister controls using allele-specific amplification. The rare form of the Q356R polymorphism was significantly ( P = 0.03) associated with a family history of ovarian cancer, suggesting that this polymorphism may influence ovarian cancer risk. In summary, our data suggest a role for some uncharacterized variants and rare forms of polymorphisms in determining ovarian cancer risk, and highlight the necessity to screen for missense alterations as well as truncating mutations in this population.
Adult↗
Profiles of endogenous circulating cortisol and bone mineral density in healthy elderly men.
Exogenous glucocorticoids are known to increase the risk of osteoporosis. However, the contribution made by endogenous circulating cortisol concentrations to adult skeletal status remains unknown. We examined this issue in a sample of 34 healthy men, aged 61-72 yr. Venous blood samples were obtained under standard conditions every 20 min over a 24-h period. Measurements were made of serum cortisol and cortisol-binding globulin. Bone mineral density was measured at the lumbar spine and proximal femur using dual energy x-ray absorptiometry. Measurements were made at baseline and 4 yr later. There was a weak negative association between integrated cortisol concentration and lumbar spine bone density (r = -0.37; P < 0.05); similar relationships (P < 0.05) existed at three of five proximal femoral sites. There were also statistically significant positive associations between the trough cortisol concentration and bone loss rate at the lumbar spine (r = 0.38; P < 0.05), femoral neck (r = 0.47; P < 0.001), and the trochanteric region (r = 0.41; P = 0.02) over the 4-yr follow-up period. The cross-sectional relationships between cortisol concentration and bone density were removed by adjustment for body mass index, but the influence on bone loss rate remained significant after adjusting for adiposity, cigarette smoking, alcohol consumption, dietary calcium intake, physical activity, and serum testosterone and estradiol levels. These observations suggest that the endogenous cortisol profile of healthy elderly men is a determinant of their bone mineral density and their rate of involutional bone loss.
Aged↗
The epidemiology of Paget's disease in Britain: is the prevalence decreasing?
To estimate changes in the age- and gender-specific prevalence of Paget's disease in Britain, we performed a radiographic survey of the disorder in 10 British centers, using sampling and radiographic methods identical to a study performed in 1974. In each center, a sample of abdominal radiographs of people aged 55 years and over was taken from stored films within the radiology department of the principal general hospital. The radiographs were identified by screening radiographic records over the period 1993-1995. Any abdominal radiograph in a subject aged 55 years and over which included the entire pelvis, sacrum, femoral heads, and all lumbar vertebrae was studied. The radiographs were evaluated by a trained observer and the consultant radiologist who participated in the original 1974 survey. Nine thousand eight hundred and twenty-eight radiographs (4625 men, 5203 women) were assessed in the 10 towns. The overall age/gender standardized prevalence rate was 2%, with a male/female ratio of 1.6. Prevalence increased steeply with age among men and women, rising to 6.9% of men and 5.8% of women aged 85 years and over. The prevalence of Paget's disease in the 10 towns in 1994 was only 40% of that observed during the 1974 study. The decline in prevalence was apparent in all 10 centers, but was most marked in those with high rates in the original study. This survey of Paget's disease in 10 British towns suggests a prevalence of 2.5% among men and 1.6% among women aged 55 years and over. Age-adjusted prevalence rates declined steeply between 1974 and 1994. These declines suggest an environmental contribution to the etiology of this disorder that requires further investigation.
Age Factors↗
The influence of fluorescent dye structure on the electrophoretic mobility of end-labeled DNA.
Over the past 10 years, fluorescent end-labeling of DNA fragments has evolved into the preferred method of DNA detection for a wide variety of applications, including DNA sequencing and PCR fragment analysis. One of the advantages inherent in fluorescent detection methods is the ability to perform multi-color analyses. Unfortunately, labeling DNA fragments with different fluorescent tags generally induces disparate relative electrophoretic mobilities for the fragments. Mobility-shift corrections must therefore be applied to the electrophoretic data to compensate for these effects. These corrections may lead to increased errors in the estimation of DNA fragment sizes and reduced confidence in DNA sequence information. Here, we present a systematic study of the relationship between dye structure and the resultant electrophoretic mobility of end-labeled DNA fragments. We have used a cyanine dye family as a paradigm and high-resolution capillary array electrophoresis (CAE) as the instrumentation platform. Our goals are to develop a general understanding of the effects of dyes on DNA electrophoretic mobility and to synthesize a family of DNA end-labels that impart identically matched mobility influences on DNA fragments. Such matched sets could be used in DNA sequencing and fragment sizing applications on capillary electrophoresis instrumentation.
Carbocyanines↗
Communication of psychiatric diagnosis.
We examined whether psychiatric patients knew their diagnosis, the significance they attached to it, and the impact of being informed in a systematic fashion according to their wishes. We also assessed whether the nature of the psychiatric diagnosis influenced what patients were told by their psychiatrists. The three parts of the study included questionnaire responses from 28 consultant psychiatrists: case-note reviews and questionnaire responses of 200 adult psychiatric in-patients: and a pilot study informing 28 adult psychiatric day hospital patients of their diagnosis according to their wishes. The results showed that of 126 in-patients, 53% had not been told their diagnosis, although most wanted to know. Of those informed, 75% agreed with their diagnosis. The majority of patients considered a psychiatric diagnosis to be as real as a physical diagnosis and helpful in their treatment. Patients with schizophrenia were less likely to have been informed of their diagnosis, and psychiatrists were also more reticent regarding the diagnosis of personality disorder. All patients who were systematically informed, in the pilot study agreed with their diagnosis. We conclude that most patients agree with their diagnosis and its usefulness. All patients should be asked whether they want to know their diagnosis and be informed appropriately.
Adolescent↗
Programming of growth hormone secretion and bone mineral density in elderly men: a hypothesis.
Epidemiological studies suggest that retarded growth in infancy is associated with low adult bone mass. The mechanism underlying this association is unknown, but the programming of GH secretion or sensitivity by environmental influences during early development may play a role. We examined this issue in a sample of 37 healthy men, aged 63-73 yr, whose weight gain in infancy had been recorded. Venous blood samples were obtained under standard conditions every 20 min over a 24-h period. Measurements were made of the GH secretory profile, insulin-like growth factor I (IGF-I), IGF-binding protein-1 and -3, and GH-binding protein. Bone mineral density was measured at the lumbar spine and femoral neck using dual energy x-ray absortiometry. There was a statistically significant association between peak GH concentration (r = 0.46; P < 0.01) and fasting IGF-I concentration (r = 0.46; P < 0.01) with femoral neck bone density. After allowing for the peak GH concentration, median GH was negatively (P < 0.05) associated with bone mineral density. Weight at 1 yr was not related to peak GH, but was strongly related to the median GH concentration (r = 0.42; P = 0.01). These observations are consistent with a dual effect of GH secretion on bone density. High peak GH values drive IGF-I production and maintain bone mineralization in adult life. However, integrated GH secretion, after adjusting for the effect of pulse amplitude, is negatively associated with bone density in adult life. This particular characteristic of the GH secretory profile correlates with growth during infancy and might be programmed by environmental factors during intrauterine or early postnatal life.
Adult↗
High mutation detection rate in the COL4A5 collagen gene in suspected Alport syndrome using PCR and direct DNA sequencing.
Approximately 85% of patients with Alport syndrome (hereditary nephritis) have been estimated to have mutations in the X chromosomal COL4A5 collagen gene; the remaining cases are autosomal with mutations in the COL4A3 or COL4A4 genes located on chromosome 2. In the present work, the promoter sequence and previously unknown intron sequences flanking exons 2 and 37 of COL4A5 were determined. Furthermore, intron sequences flanking the other 49 exons were expanded from 35 to 190 to facilitate mutation analysis of the gene. Using this information, all 51 exons and the promoter region were PCR-amplified and sequenced from DNA of 50 randomly chosen patients with suspected Alport syndrome. Mutations were found in 41 patients, giving a mutation detection rate of 82%. Retrospective analysis of clinical data revealed that two of the cases might be autosomal. Although it could not be determined whether the remaining seven cases (14%) were autosomal or X chromosome-linked, it is likely that some of them were autosomal. It is concluded that PCR amplification and direct DNA sequencing of the promoter and exons is currently the best procedure to detect mutations in COL4A5 in Alport syndrome.
Amino Acid Substitution↗
An investigation into the relationships between area social characteristics and road accident casualties.
This paper reports on the analysis of a data base created by merging road casualty information and census data for the former Lothian region in Scotland. The data base was established by assigning resident postcodes to each casualty record and relating these postcodes to the census data for the relevant census output area. Initially, consideration was given to the relationship between casualty frequencies and the distance of the accidents from the zones of residence. As might be anticipated, the casualty frequencies were higher nearer to the zones of residence, possibly due to higher exposure. Subsequently, the relationships between casualty rates and social deprivation indicators for the casualties' zone of residence were investigated. In general it was found that the casualty rates amongst residents from areas classified as relatively deprived were significantly higher than those from relatively affluent areas.
Accidents, Traffic↗
Physical and sexual abuse of children in the West Midlands.
OBJECTIVE: To describe the convicted and cautioned abusers and the nature of the physical and sexual abuse of children using a legal classification in an attempt to formulate operational criteria for future comparative studies. DESIGN: A retrospective sequential survey of all cautioned and convicted physical and sexual abusers between the January 1, 1988 and June 30, 1994. SETTING: The West Midlands police jurisdiction. SUBJECTS: 1,113 abused children and 964 abusers. RESULTS: The majority of all abuse involved a single child. Many abusers lived in the same household and were in a position of trust or quasi-trust. When strangers committed abuse, the majority of abuse was sexual. A third of the abusers were unemployed. Multiple abuse tended to be sexual and was perpetrated by men. The physical abuse of young children tended to be committed by younger women. No women over the age of 40 had sexually abused a child. Of the children under 12 months, 1.5% had been sexually abused and 8.5% had been physically abused. The greater proportion of physical abuse had occurred in children under 9 years of age whereas sexual abuse was perpetrated more often in girls aged 9 to 11 years. No girls were murdered in this survey. Significantly more boys had been buggered. CONCLUSION: This preliminary study is representative of all the cautioned and convicted cases within the selected 5-year period and obtained from a source of material hitherto unavailable. Many of the findings of this preliminary study are in line with previous studies. Substantial descriptive information has been obtained on a selected population of cautioned or convicted abusers. Further studies may indicate that the cautioned and convicted are more representative of abusers generally than previously thought. Expanded studies may eventually produce particularized profiles of both abusers and the abused, but even the limited guidance provided by this preliminary study will give some assistance to law enforcement agencies in detection and child protection agencies in identifying children at risk and targeting resources more efficiently.
Adolescent↗
Efficiency of the OVATEC unit for estrus detection and calf sex control in beef cows.
Seventy five spring calving Gelbvieh and Angus cows were utilized over a three year period to evaluate the usefulness of the OVATEC intravaginal probe for indicating the onset of estrus and providing the possibility to influence the sex of the offspring by choosing a breeding time in relation to critical changes in cervical mucus conductivity. Cows were randomly assigned by breed each year into one of four treatments: (1) probed and inseminated when impedance values declined, creating conditions expected to favor X-bearing sperm and with it an increase in the conception of females (PF); (2) probed and inseminated when impedance values were rebounding, expected to favor Y-bearing sperms and with it an increase in the conception of males (PB); (3) standing estrus (AI); or (4) natural service by bull (NS). Cows grazed or were fed hay from tall fescue-legume pastures. Lutalyse was used to synchronize estrus in a two injection scheme. Vaginal probe readings were taken at first injection, second injection and every 12 h thereafter for 6 days. Visual observations for estrus were obtained for PF, PB and AI every 12 h postsecond injection. Rectal palpations of ovaries were obtained at standing heat in all but NS treatments. In cycling cows, probe readings increased prediction of estrus onset (P < 0.10) compared to visual observations and were similar (P > 0.95) to rectal palpations in all probed cows. PF cows delivered heifer calves at greater rates (P < 0.025) than all other treatments whereas PB cows delivered bulls at greater rates (P < 0.05) than all other treatments. Heifer to bull ratios were not different (P > 0.95) for AI or NS treatments. The results of this study indicate that the potential exists for increasing female offspring conceptions utilizing cervical mucus conductivity as a gauge for insemination times.
Administration, Intravaginal↗
Silicone oil adhesion to intraocular lenses: an experimental study comparing various biomaterials.
PURPOSE: To perform an in vitro experimental study comparing the degree of adherence of silicone oil to various rigid and foldable intraocular lens (IOL) designs and to the human lens capsule. SETTING: Center for Research on Ocular Therapeutics and Biodevices, Department of Ophthalmology, Storm Eye Institute, Medical University of South Carolina, Charleston, South Carolina, USA. METHODS: Seven IOL styles comprising various biomaterials were studied: fluorine-treated (Fluorlens), heparin-surface-modified (HSM), hydrogel, Memory-Lens, Poly(methyl methacrylate) (PMMA), soft acrylic, and silicone lenses; the human crystalline lens was also studied. Each lens was immersed in silicone oil for 12 hours, than photographed, studied by scanning electron microscopy (except the crystalline lens), and subjected to computer-generated image analysis to determine the silicone oil coverage. RESULTS: Silicone oil coverage of dry silicone lenses was 100% and of lenses immersed in normal saline, 82.5%. The least coverage was on the heparin-surface-modified lens (mean score 9.4%). Coverage of the other four lenses ranged from approximately 15.1% to 33.7%. Mean coverage of the human lens capsule was 10.9%. CONCLUSION: Although a silicone IOL shows maximal adherence to silicone oil, other lens biomaterials are not immune to this complication. Silicone oil coverage was related to the dispersive energy component of the surface charge of the IOL biomaterial. Low dispersive energy materials had less silicone oil coverage, while those with higher dispersive energy had more oil coverage.
Adhesiveness↗
Retinal vascular network architecture in low-birth-weight men.
BACKGROUND: Low birth weight is associated with hypertension and increased cardiovascular mortality, but the mechanism of this association is not known. Hypertension is accompanied by abnormalities of the microvasculature including rarefaction. OBJECTIVE: To test the hypothesis that low birth weight is associated with an alteration in microvascular architecture. DESIGN: A stratified random sample of 100 men aged 64-74 years was selected from a cohort of men whose birth weights were known. They were of relatively high or low birth weight ('high' > or = 3700 g, 'low' < or = 3200 g) and high or low systolic blood pressure (high > or = 160 mmHg, low < or = 140 mmHg). METHODS: Retinal arteriolar geometry was defined in terms of arteriolar bifurcation angles and junction exponents (a measure of the relative diameters of parent and daughter vessels), measured from photographic diapositives using operator-directed image analysis. RESULTS: Members of low-birth-weight groups had significantly narrower bifurcation angles than did members of high-birth-weight groups (74 +/- 1 degree versus 78 +/- 1 degree, P= 0.017 by analysis of variance). There was no significant difference between angles in members of groups with high and low blood pressures. Neither birth weight nor blood pressure grouping affected junction exponents. CONCLUSIONS: Narrower bifurcation angles are associated with increased circulatory energy costs and may be related to a lower than normal microvascular density. Our finding of differences in retinal microvascular architecture might reflect a persistent alteration in vascular architecture as a result of an impairment of foetal development and could provide a mechanistic link between low birth weight and subsequently increased cardiovascular risk.
Aged↗
Growth in infancy and bone mass in later life.
OBJECTIVE: To examine the association between weight in infancy and bone mass during the seventh decade of life in a population based cohort for which detailed birth and childhood records were preserved. METHODS: 189 women and 224 men who were aged 63-73 years and were born in East Hertfordshire underwent bone densitometry by dual energy x ray absorptiometry. Measurements were also made of serum osteocalcin and urinary excretion of type 1 collagen cross linked N-telopeptide. RESULTS: There were statistically significant associations between weight at 1 year and bone mineral content (but not bone mineral density) at the spine (P < 0.02) and femoral neck (P < 0.01) among women, and spine (P < 0.03) among men. Although serum osteocalcin was negatively correlated with bone mineral density at both sites among men and women, infant weight was not significantly associated with either biochemical marker of bone turnover. CONCLUSIONS: These data confirm our previous observations that growth in infancy is associated with skeletal size in adulthood, and suggest that skeletal growth may be programmed during intrauterine or early postnatal life.
Aged↗
Prenatal factors influencing long-term outcome.
Animal studies have shown that undernutrition before birth programmes persisting changes in a range of metabolic, physiological and structural parameters. Studies in humans have shown that men and women who had birth weights at the lower end of the normal range, who were thin or short at birth, or who were small in relation to placental size, have increased rates of coronary heart disease. This article suggests how fetal undernutrition at different stages of gestation may be linked to these patterns of early growth. Adaptations by the fetus to undernutrition are associated with changes in the concentrations of fetal placental hormones. Persisting changes in the level of hormone secretion and tissue sensitivity may link fetal undernutrition with adult disease.
Adult↗
Childhood growth and age at menarche.
OBJECTIVE: To study the influence of birthweight, and weight and height at age seven years, on menarcheal age in a national sample of 1471 girls in England, Scotland and Wales. METHODS: We studied 1471 girls included in the MRC National Survey of Health and Development. During medical examinations carried out by school doctors in this cohort, born in the first week of March 1946, the mothers of girls were asked whether their daughters had started to menstruate, and if so, the month and year when this happened. Anthropometric measurements at birth and at age seven years were also obtained. RESULTS: Girls who were heavier at age seven years had menarche at an earlier age. The average age at menarche of those in the highest fifth of the distribution of weight at seven years was 7.3 months less than that of those in the lowest fifth of the distribution. In contrast, girls who were heavier at birth had menarche at a later age. The average age at menarche of those in the highest fifth of the birthweight distribution was 2.2 months more than those in the lowest fifth. These opposing trends of birthweight and weight at seven years on age at menarche were observed across the distribution of each variable, and exerted statistically significant (P < 0.001) independent effects in a multivariate model. CONCLUSIONS: These observations are consistent with the hypothesis that menarcheal age is linked to programmed patterns of gonadotrophin release established in utero, when the fetal hypothalamus is imprinted, and is subsequently modified by weight gain in childhood.
Adolescent↗
Identification of 17 mutations in ten exons in the COL4A5 collagen gene, but no mutations found in four exons in COL4A6: a study of 250 patients with hematuria and suspected of having Alport syndrome.
Conditions for polymerase chain-reaction amplification of ten exon regions (Exons 3, 7, 11 through 13, and 15 through 19) of the collagen COL4A5 gene and four exon regions (Exons 2, and 12 through 14) of the COL4A6 gene were sequenced and established in this study. These Type IV collagen genes contain 51 and 48 exons, respectively. The sequences of these exons were determined in the two genes in 250 male patients with hematuria and suspected Alport syndrome. Seventeen mutations were found in nine of the ten exons studied in the COL4A5 gene in 17 patients, whereas no mutations were identified in COL4A6. One mutation was identical in two patients known to be unrelated. The results indicate that mutations in COL4A5 that leading to renal failure are more frequent than those involved in classic Alport syndrome, and also that mutations in COL4A6 are not likely to cause this disease. Furthermore, mutations in COL4A5 are distributed quite randomly and no "hot spots" were found.
Adolescent↗
Immunomagnetic separation can enrich fixed solid tumors for epithelial cells.
Immunomagnetic separation is a highly specific technique for the enrichment or isolation of cells from a variety of fresh tissues and microorganisms or molecules from suspensions. Because new techniques for molecular analysis of solid tumors are now applicable to fixed tissue but sometimes require or benefit from enrichment for tumor cells, we tested the efficacy of immunomagnetic separation for enriching fixed solid tumors for malignant epithelial cells. We applied it to two different tumors and fixation methods to separate neoplastic from non-neoplastic cells in primary colorectal cancers and metastatic breast cancers, and were able to enrich to a high degree of purity. Immunomagnetic separation was effective in unembedded fixed tissue as well as fixed paraffin-embedded tissue. The magnetically separated cells were amenable to fluorescence in situ hybridization and polymerase chain reaction amplification of their DNA with minimal additional manipulation. The high degree of enrichment achieved before amplification contributed to interpretation of loss of heterozygosity in metastatic breast cancers, and simplified fluorescence in situ hybridization analysis because only neoplastic cells were hybridized and counted. Immunomagnetic separation is effective for the enrichment of fixed solid tumors, can be performed with widely available commercial antibodies, and requires little specialized instrumentation. It can contribute to interpretation of results in situations where enrichment by other methods is difficult or not possible.
Breast Neoplasms↗