A suggested methodology for the construction of national bone density reference ranges: 1372 Caucasian women from four UK sites.
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Biomedical subjects
Publications and source records attributed to C Cooper.
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OBJECTIVE: We conducted a survey of the members of the Society of Computed Body Tomography/Magnetic Resonance to assess current techniques in liver imaging using helical CT. MATERIALS AND METHODS: The survey, which was designed to update earlier surveys from 1987 and 1993, included a questionnaire distributed to 77 members of the Society of Computed Body Tomography/Magnetic Resonance. RESULTS: Forty-nine members responded, representing 28 institutions. In 1993, 19% (5/26) of institutions used helical scanners, compared with 82% (23/28) in 1996. The group of institutions with helical CT served as the focus of this survey. In 1993, 58% of institutions used 1-cm collimation: in 1996, 78% (18/23) used thinner, 7- to 8-mm collimation. In 1987, 41% used power injectors compared with 85% in 1993 and 100% in 1996. In 1996, monophasic injections were used by 96% (22/23) of institutions. In 1993, most institutions used a contrast material injection rate of 1.5-2.0 ml/sec; in 1996, most used a 2.5-3.0 ml/sec injection rate. In 1993, 96% of institutions used 125-150 ml of contrast material; in 1996, 57% (13/23) of institutions used 125-150 ml and 30% of institutions used less than 125 ml of contrast material. A delay time of 21-45 see was used by 83% of institutions in 1993, whereas in 1996, 83% (19/23) of institutions used a longer delay time of 50-80 sec. In 1996, 13% of institutions used an individual scan delay technology and all institutions performed multiphasic scanning of hypervascular lesions. CONCLUSION: The availability of helical CT has changed radiologists' approach to liver imaging. The greatest effects of which are a more widespread use of power injectors, longer delay times, thinner collimation, increased contrast material injection rates, decreased contrast material volumes, and multiphasic scanning.
Plasma concentrations of lipoprotein (a) [Lp(a)] are increased in patients on renal replacement therapy. Lipoprotein (a) is increasingly being recognized as an independent cardiovascular risk factor. In an effort to explore the mechanism for elevation of Lp(a) in patients on dialysis we have performed turnover studies of Lp(a) with radioactive iodine. Lp(a) was isolated from 1 patient on hemodialysis (HD) and 1 patient on continuous ambulatory peritoneal dialysis (CAPD); the protein was labeled with 125I and returned to each patient. Lipoprotein (a) was subsequently isolated from the patients over a 15-day period and the decay of the specific radioactivity of Lp(a) was used to determine the fractional catabolic rate (FCR), which was 0.27 (pool/day) for the HD patient and 0.28 (pool/day) for the CAPD patient. These rates are indistinguishable from those measured in 4 patients with hypercholesterolemia (0.29, SEM = 0.01) and in 4 other familial hypercholesterolemic patients (0.29, SEM = 0.02) studied previously using the same method by Knight et al. (7). We found no difference in the FCR of patients on dialysis when compared to patients with hyperlipidemia and normal renal function. Increased plasma concentration of Lp(a) in our patients on renal replacement therapy is not due to decreased catabolism, but is caused by increased synthesis.
The Aquarius underwater laboratory (or habitat) is the world's only operational saturation facility currently supporting scientific research and is operated by the University of North Carolina at Wilmington. The underwater laboratory accommodates and supports six aquanauts (scientists and habitat technicians) at habitat depth for 10-30-day missions. In the past, life support systems were provided by a manned support barge or Mobile Support Base (MSB) moored directly above Aquarius. The MSB was manned 24 h a day during saturation missions, which required 12 support staff in three separate shifts. A new unmanned Life Support Buoy (LSB) replaces the MSB and provides life support systems and is the voice, video, and data communications bridge from the habitat to the shore base. The LSB transmits status of all life support systems to the habitat and the shore base, thus minimizing the need for support staff to be present overtop of Aquarius during missions.
Fourteen cases of an atypical myeloproliferative disorder associated with consistent translocations involving 8p11-12 have previously been described. A t(8;13)(p11;q11-12) was the most common, but variant t(8;9)(p11-12;q32-34) and t(6;8)(q27;p12) were also reported. Here we have used a series of yeast artificial chromosomes (YACs) derived from the 8p11 and 13q11-12 regions to analyse one of the t(8;13) cases by fluorescence in situ hybridization (FISH). YACs flanking the 13q11-12 breakpoint and spanning the 8p11 breakpoint have been isolated. These YACs will facilitate characterization of the genes involved in this rearrangement.
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PURPOSE: The aim of this study was to assess the relationship between fetal and infant growth, as measured by birthweight and weight at 1 year and the development of age-related lens opacities. METHODS: A total of 1428 men and women who were born in Hertfordshire, United Kingdom, between 1920 and 1930, and for whom records of birthweight and weight at 1 year were available, were traced and invited for examination. Of these, 717 (50%) attended for ophthalmic examination. After dilation with tropicamide 1%, lens opacities were graded using the Lens Opacities Classification System (LOCS) III. RESULTS: In this population of English men and women aged 64 to 74 years, most opacities were of the nuclear type. There was no association between birthweight and nuclear lens opacities. Weight at 1 year was negatively correlated with nuclear opacity score in adult life (P=0.001). Subjects in the highest tertile for weight at 1 year (>23 pounds) had an odds ratio of 0.35 (95% confidence interval, 0.17 to 0.74) for having a significant nuclear lens opacity (LOCS score of > or = 3) compared with people in the lowest tertile for weight at 1 year (<21 pounds). This association remained after controlling for age, sex, smoking, social class, adult height, and diabetes. CONCLUSIONS: To our knowledge, this is the first time that such an association has been reported; it needs to be replicated in other populations. It could provide part of the explanation for the observed excess risk of cataract in developing countries.
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The histone H4 gene promoter provides a paradigm for defining transcriptional control operative at the G1/S phase transition point in the cell cycle. Transcription of the cell cycle-dependent histone H4 gene is upregulated at the onset of S phase, and the cell cycle control element that mediates this activation has been functionally mapped to a proximal promoter domain designated Site II. Activity of Site II is regulated by an E2F-independent mechanism involving binding of the oncoprotein IRF2 and the multisubunit protein HiNF-D, which contains the homeodomain CDP/cut, CDC2, cyclin A, and the tumor suppressor pRb. To address mechanisms that define interactions of Site II regulatory factors with this cell cycle control element, we have investigated these determinants of transcriptional regulation at the G1/S phase transition in FDC-P1 hematopoietic progenitor cells. The representation and activities of histone gene regulatory factors were examined as a function of FDC-P1 growth stimulation. We find striking differences in expression of the pRb-related growth regulatory proteins (pRb/p105, pRb2/p130, and p107) following the onset of proliferation. pRb2/p130 is present at elevated levels in quiescent cells and declines following growth stimulation. By contrast, pRb and p107 are minimally represented in quiescent FDC-P1 cells but are upregulated at the G1/S phase transition point. We also observe a dramatic upregulation of the cellular levels of pRb2/p130-associated protein kinase activity when S phase is initiated. Selective interactions of pRb and p107 with CDP/cut are observed during the FDC-P1 cell cycle and suggest functional linkage to competency for DNA binding and/or transcriptional activity. These results are particularly significant in the context of hematopoietic differentiation where stringent control of the cell cycle program is requisite for expanding the stem cell population during development and tissue renewal.
Around 40% of white women and 13% of white men in the United States have at least one fragility fracture after the age of 50 years. The risk of fracture increases with advancing age and progressive loss of bone mass, and varies with the population being considered. The age-adjusted incidence of fragility fractures in both sexes is 25% lower in Britain and many areas of Europe than in the United States. Mortality 5 years after hip or vertebral fracture is about 20% in excess of that expected; mortality rate is highest in men > 75 years suffering from a variety of chronic diseases. Most excess deaths occur in the first 6 months after hip fracture. One year after hip fracture, 40% of patients are still unable to walk independently, 60% have difficulty with at least one essential activity of daily living, and 80% are restricted in other activities, such as driving and grocery shopping. Moreover, 27% of these patients enter a nursing home for the first time. Less is known of the epidemiology of vertebral fractures and of the associated mortality and morbidity. Although an estimated 30% of postmenopausal U.S. white women have osteoporosis, and 1 in 4 has at least one vertebral deformity, two thirds of vertebral fractures remain undiagnosed. After a clinically diagnosed vertebral fracture, survival rate decreases gradually from that expected without fracture. Women with severe vertebral deformities have a consistently higher risk of back pain and height loss. An accurate assessment of the risk of fractures associated with osteoporosis and of their impact on quality of life is essential if appropriate and cost-effective interventions are to be designed for different populations.
To investigate the association between anthropometric indices and morphometrically determined vertebral deformity, the authors carried out a cross-sectional study using data from the European Vertebral Osteoporosis Study (EVOS), a population-based study of vertebral osteoporosis in 36 European centers from 19 countries. A total of 16,047 EVOS subjects were included in this analysis, of whom 1,973 subjects (915 males, 1,058 females) (12.3%) aged 50 years or over had one or more vertebral deformities ("cases"). The cases were compared with the 14,074 subjects (6,539 males, 7,535 females) with morphometrically normal spines ("controls"). Data were collected on self-reported height at age 25 years and minimum weight after age 25 years, as well as on current measured height and weight. Body mass index (BMI) and height and weight change were calculated from these data. The relations between these variables and vertebral deformity were examined separately by sex with logistic regression adjusting for age, smoking, and physical activity. In females, there was a significant trend of decreasing risk with increasing quintile of current weight, current BMI, and weight gain since age 25 years. In males, subjects in the lightest quintile for these measures were at increased risk but there was no evidence of a trend. An ecologic analysis by country revealed a negative correlation between mean BMI and the prevalence of deformity in females but not in males. The authors conclude that low body weight is associated with presence of vertebral deformity.
Condensed roofing asphalt fumes, generated at 316 degrees C, were collected by cold trap condensation and fractionated by preparative high performance liquid chromatography. Chemical classes in each of the fractions (A-E) were identified by gas chromatography/mass spectroscopy. The fractions, various combinations of fractions, the raw and heated asphalt, the neat asphalt fume and the reconstituted asphalt were tested for carcinogenicity, and three fractions were tested for cocarcinogenicity and tumor promotion with benzo[a]pyrene (BaP). The skin application carcinogenesis bioassay was conducted by twice weekly application of test materials in 0.05 ml of acetone/cyclohexane (1:1) for 104 weeks to 40 groups of male C3H/HeJ mice (30/group). Fractions were applied at a mass in proportion to their amount in the neat asphalt fumes. In addition, the neat asphalt fume was tested on Sencar mice to determine if this strain was more susceptible to the carcinogenic effects of the fumes. Condensed neat asphalt fumes produced similar and statistically significant increased tumor yields of papillomas and carcinomas in both strains as compared to respective vehicle controls. Recombination of all fractions resulted in a tumor response similar to neat asphalt fumes. Among individual fractions, C was most potent, followed by B. The other single fractions were without significant tumorigenic activity. Combinations containing fractions B and C were most active among the mixtures that were assayed and no evidence of enhancement of tumorigenesis in the mixtures was found. No significant cocarcinogenic or tumor promoting activity was observed with fractions A, D, or E and BaP. Raw unheated asphalt produced a few tumors in C3H mice, but no tumors were seen when raw asphalt heated to 316 degrees C, with the fumes permitted to escape, was applied.
Nonobese diabetic (NOD) mice develop an anti-exocrine gland pathology similar to human Sjögren syndrome. Recently, we demonstrated that NOD-scid mice develop severe loss of submandibular acinar cells with concomitant appearance of abnormal isoforms of salivary proteins suggesting de novo enzymatic cleavage. Because these changes may indicate activation of apoptotic proteases, we examined saliva and salivary tissue for cysteine protease activity. Cysteine protease activities were elevated in saliva and gland lysates from 20-week-old NOD and NOD-scid mice as compared with age- and sex-matched BALB/c or 8-week-old NOD mice. This activity appeared in the submandibular glands, but not in the parotid glands. Western blot analyses using antibodies directed against specific apoptotic proteases (interleukin 1beta converting enzyme, Nedd-2, and Apopain/CPP 32) confirmed these findings. Submandibular glands from NOD-scid mice exhibited the greatest increase in proteolytic activity, indicating that infiltrating leukocytes are not responsible for these changes. Western blot analyses also failed to reveal changes in the levels of cystatins (saliva proteins that inhibit protease activity). Thus, increased cysteine protease activity appears to be directly related to submandibular acinar cell loss in NOD-scid mice involving the apoptotic pathway. Additional protease activity in saliva and gland lysates of older NOD and NOD-scid mice, apparently mutually distinct from cysteine proteases, generated an enzymatically cleaved parotid secretory protein. We suggest, therefore, that proteolytic enzyme activity contributes to loss of exocrine gland tolerance by generating abnormally processed protein constituents.
OBJECTIVE: To assess the impact of handling patients and indicators of individual susceptibility on risk of low back pain in nurses. DESIGN: Prospective cohort study with follow up by repeated self administered every three months over two years. SETTING: NHS university hospital trust. SUBJECTS: 961 female nurses who had been free from low back pain for at least one month at the time of completing a baseline questionnaire. MAIN OUTCOME MEASURES: Incidence of new low back pain during follow up and of pain leading to absence from work. RESULTS: Of 838 women who provided data suitable for analysis, 322 (38%) developed low back pain during follow up (mean 18.6 months), including 93 (11%) whose pain led to absence from work. The strongest predictor of new low back pain was earlier history of the symptom, and risk was particularly high if previous pain had lasted for over a month in total and had occurred within the 12 months before entry to the study (incidence during follow up 66%). Frequent low mood at baseline was strongly associated with subsequent absence from work for back pain (odds ratio 3.4; 95% confidence interval 1.4 to 8.2). After adjustment for earlier history of back pain and other potential confounders, risk was higher in nurses who reported frequent manual transfer of patients between bed and chair, manual repositioning of patients on the bed, and lifting patients in or out of the bath with a hoist. CONCLUSIONS: Of the indicators of individual susceptibility that were examined, only history of back trouble was sufficiently predictive to justify selective exclusion of some applicants for nursing posts. The main route to prevention of back disorders among nurses is likely to lie in improved ergonomics.
The objective of this article is to assess the validity of data on occupational activities obtained by a questionnaire. 152 employees from 16 jobs were interviewed independently about activities in their work, using a structured questionnaire. For 11 of the jobs, two further workers were observed during a typical shift, and their activities recorded. The agreement of reporting between subjects doing the same job and with observation was assessed. There was good agreement between subjects and with observation for most of the activities examined when the activities were classified dichotomously. However, frequency of heavy lifting was reported inconsistently. Questionnaires are able to distinguish major differences in physical activity that occur between jobs in the general population, but do not allow more detailed quantification of activities.
The objective of this work was to address the relationship between physical activity in the workplace and subsequent musculoskeletal pain syndromes. We performed a survey of 5,042 men and women aged 70-75 years, selected from the retirement population of a large national employer (the post office). Subjects were sent a short postal questionnaire enquiring about all occupations held for at least 1 year, the physical activities performed in those jobs, and about recent rheumatic symptoms. The 1-month period prevalence of rheumatic symptoms ranged from 19.9% for hip pain or stiffness in men to 50% for knee pain or stiffness in women. Symptoms were more common in women than men at all sites and there were significant (P < 0.001) associations between symptoms at different sites. Obesity was significantly (P < 0.001) associated with the risk of pain or stiffness at the knee and hip. Prolonged occupational exposure (20+ years) to heavy lifting was associated with hip pain (RR = 1.5; 95% CI = 1.2-1.8); and prolonged exposure to working with arms elevated was associated with an increased risk of shoulder pain (RR = 1.4; 95% CI = 1.2-1.6). Tall stature (P = 0.003) and heavy lifting (P < 0.001) were both associated with increased risks of low back pain among men. This survey confirms the high prevalence of musculoskeletal symptoms observed in previous population-based studies. Associations between occupational activities and musculoskeletal symptoms were specific for activity type and skeletal site involved. Our results imply that the adverse effects of these occupational activities can be found many years after cessation of exposure.
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