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Biomedical subjects

C Cooper

Publications and source records attributed to C Cooper.

At least 109 records · Page 6Linked to original sources

Reference ranges of bone mineral density for women in southern England: the impact of local data on the diagnosis of osteoporosis.

The construction of reference ranges that accurately represent the population at large is essential for the correct identification of osteoporosis from bone mineral density (BMD) measurements. In this study, reference data supplied by the manufacturer of the Lunar DPX+ bone densitometer were compared with data obtained locally. Lumbar spine, proximal femur and total body BMD measurements were made in an age-stratified random sample of 702 Southampton women aged 20 to 89 years. Relevant demographic and medical data were recorded for each subject using a questionnaire. Reference curves of BMD (mean +/- SD) were plotted against age for each measurement site and were found to be higher than the manufacturer's reference values at all ages and sites. Exclusion of women with factors known to affect bone mass only served to increase this discrepancy. According to World Health Organisation definitions, osteoporosis may be identified from BMD values alone. Based upon neck of femur BMD values, 100 (14.8%) of the women in this study group were categorized as osteoporotic using local young normal reference data, compared with only 39 (5.8%) using the manufacturer's data. By normalizing for age distribution, these findings were extrapolated to the local population where it was predicted that 26.0% and 10.1% of females over 50 years of age would be classified as osteoporotic using the respective reference ranges. This study clearly illustrates how the numbers of women diagnosed as osteoporotic vary with the use of different reference populations.

Adult

Assessment of a technology that permits individualized scan delays on helical hepatic CT: a technique to improve efficiency in use of contrast material.

OBJECTIVE: We performed this study to assess the usefulness of a computer automated scan technology (CAST) for individualizing scan delay during helical CT to improve the efficiency of hepatic enhancement. SUBJECTS AND METHODS: We prospectively evaluated 183 patients who were randomized into five groups. Control patients received 100 or 150 ml of contrast material (320 mg I/ml) with a 60-sec delay between contrast injection at 3 ml/sec and scanning. CAST patients received 100, 125, or 150 ml. In our latter groups we used an hepatic enhancement threshold of 50 H over baseline to determine the optimum delay between contrast injection and scanning. For the intergroup comparisons, we measured the liver on baseline and enhanced helical CT scans at the upper, mid, and lower levels of the liver. RESULTS: The mean enhancement in patients who received 150 ml of contrast material was 70.7 +/- 19.4 H for the control group and 81.0 +/- 17.5 H for the CAST group (p < .05). Hepatic enhancement above 50 H was achieved in 84% of the control subjects compared with 100% of CAST subjects; more than 60 H hepatic enhancement was achieved in 73% of control subjects and in 89% of CAST subjects. The use of CAST software with 125-ml contrast doses provided enhancement equivalent to that of control subjects who received 150 ml of contrast material (mean enhancement in CAST subjects, 70.3 +/- 15.4 H). Enhancement above 50 H was reached in 98% of CAST and 84% of control patients. With 100 ml of contrast material, 24% of patients failed to initiate CAST, resulting in enhancement similar to control patients (CAST, 54.2 +/- 11.4 H; controls, 56.9 +/- 15.2 H). CONCLUSION: Using a contrast dose of 150 ml, CAST provided significantly increased hepatic enhancement than that achieved in control subjects with less variability. For equivalent hepatic enhancement, contrast doses could be decreased by 25 ml using CAST technology because it provides individualized scan delays.

Adult

Helical CT of renal masses: the value of delayed scans.

OBJECTIVE: Routine scanning techniques used for helical CT of the abdomen result in dense cortical opacification of the kidney, whereas the medulla and collecting system are not well opacified, which potentially compromises detection of renal masses. The purpose of this retrospective study was to determine if additional delayed views (taken approximately 2-4 min after the start of injection of contrast material) are necessary for the detection and characterization of renal masses. MATERIALS AND METHODS: Early (60-70 sec after the start of the injection of contrast material) and delayed scans of 40 patients with suspected renal masses were blindly evaluated by two observers. The patients harbored a total of 187 renal masses (including 62 solid masses). Each region of the kidney (upper, middle, and lower pole) was scored for the presence of a mass. Scoring was done as a binary decision and also as a five-point confidence score for receiver operating characteristic analysis. RESULTS: We found 97 regions that contained renal masses and 114 regions that did not. Receiver operating characteristic analysis revealed the observers to have significantly greater confidence in detection of renal masses on the delayed scans. The binary data showed the two observers to have a sensitivity of 97% for delayed scans versus 77% (p = .0002) and 89% (p = .027), respectively, for the early scans. For the first observer, early and delayed scans were of equal specificity, but for the second observer, the delayed scans yielded greater specificity (94% versus 85%, p = .024). On the early scans, both observers were significantly more likely to miss a neoplastic lesion than a nonneoplastic lesion. The less experienced of the two observers also tended to have greater difficulty in characterizing the lesions on the early scans. CONCLUSION: Because of the significant risk of missing a renal mass, especially a neoplasm, on early cortical-phase scans, additional delayed scans appear justified when a renal mass is suspected on the basis of other imaging tests or clinical history.

Adult

The development of a European questionnaire for quality of life in patients with vertebral osteoporosis.

The complaints of vertebral osteoporosis usually result from wedge or crush fractures and biconcave deformities. These are caused by a decrease of bone mass and deterioration of bone structure leading to loss of strength. Treatment of osteoporosis should result in an increase of bone mass, and the incidence of new vertebral fractures should diminish. However, new vertebral fractures are not always accompanied by pain, and disability does not well correlate with the number of vertebral fractures. Patients with osteoporosis often have other problems e.g. with taking a shower, preparing meals, gardening, walking stairs, visiting friends and attending social activities. In addition, pain and disability may influence mood and lead to depression. The assessment of quality of life should be a primary endpoint in clinical trials in patients with osteoporosis and in individual patients care. Recently, the European Foundation for Osteoporosis (EFFO) has decided a develop a questionnaire for patients with vertebral osteoporosis, i.e. patients with vertebral deformities. The questionnaire is meant for use in clinical trials. A questionnaire was made including 48 questions and 6 visual analogue scales. The questions concern the following domains: pain, activities of daily living, jobs around the house, moving, leisure and social activities, general health perception and mood. The questionnaire ("Qualeffo") has now entered the validation phase. The first study in 8 centres concerns the within-subject reproducibility, the internal coherence, and the specificity by comparing osteoporotic patients with a control group not suffering from osteoporosis or backpain.

Humans

Interphase fluorescence in situ hybridization and reverse transcription polymerase chain reaction as a diagnostic aid for synovial sarcoma.

Identification of the t(X;18)(p11.2;q11.2) that is associated with a high proportion of synovial sarcoma can be a useful diagnostic aid. The translocation results in fusion of the SYT gene on chromosome 18 to either the SSX1 or the SSX2 gene, two homologous genes within Xp11.2. Two-color interphase fluorescence in situ hybridization and reverse transcription polymerase chain reaction were assessed as approaches to identify the rearrangement in well characterized cases. The presence of the translocation, and the specific chromosome X gene disrupted, were inferred from the configuration of signals from chromosome-specific centromere probes, paints, and markers flanking each gene in preparations of interphase nuclei. Rearrangement was found in two cell lines and eight of nine tumor samples, including analysis of five touch imprints. This was consistent with cytogenetic data in four cases and reverse transcription polymerase chain reaction analysis using primers known to amplify both SYT-SSX1 and SYT-SSX2 transcripts. The transcripts were distinguished by restriction with LspI and SmaI. Contrary to previous suggestions, there was no obvious correlation between histological subtype and involvement of the SSX1 or SSX2 gene. These approaches could also be applied to the identification of tumor-free margins and metastatic disease.

Adolescent

The epidemiology of osteoporosis. The oriental perspective in a world context.

In the past 3 decades, the incidence of osteoporotic hip fracture increased in Hong Kong Chinese by 2-fold to reach an incidence of approximately 10 per 1000 in women and men who are 70 years of age or older. It has been projected that 50% of all hip fractures in the world will occur in Asia by the next century. The bone mineral density of Asian populations is comparable to that of whites after adjusting for height and weight. Physical inactivity, a low dietary calcium intake, and falls have been found to be major risk factors for hip fractures in Asia. Other risk factors are cigarette smoking, heavy alcohol consumption, and multiparity. Population strategies to increase physical activity and calcium intake and to prevent falls in Oriental populations will be effective in the prevention of osteoporosis and hip fracture because of the high attributable risk for these factors.

Adult

Water fluoridation and osteoporotic fracture.

Osteoporotic fractures constitute a major public health problem. These fractures typically occur at the hip, spine and distal forearm. Their pathogenesis is heterogeneous, with contributions from both bone strength and trauma. Water fluoridation has been widely proposed for its dental health benefits, but concerns have been raised about the balance of skeletal risks and benefits of this measure. Fluoride has potent effects on bone cell function, bone structure and bone strength. These effects are mediated by the incorporation of fluoride ions in bone crystals to form fluoroapatite, and through an increase in osteoblast activity. It is believed that a minimum serum fluoride level of 100 ng/ml must be achieved before osteoblasts will be stimulated. Serum levels associated with drinking water fluoridated to 1 ppm are usually several times lower than this value, but may reach this threshold at concentrations of 4 ppm in the drinking water. Animal studies suggest no effect of low-level (0-3 ppm) fluoride intake on bone strength, but a possible decrease at higher levels. Sodium fluoride has been used to treat established osteoporosis for nearly 30 years. Recent trials of this agent, prescribed at high doses, have suggested that despite a marked increase in bone mineral density, there is no concomitant reduction in vertebral fracture incidence. Furthermore, the increase in bone density at the lumbar spine may be achieved at the expense of bone mineral in the peripheral cortical skeleton. As a consequence, high dose sodium fluoride (80 mg daily) is not currently used to treat osteoporosis. At lower doses, recent trials have suggested a beneficial effect on both bone density and fracture. The majority of epidemiological evidence regarding the effect of fluoridated drinking water on hip fracture incidence is based on ecological comparisons. Although one Finnish study suggested that hip fracture rates in a town with fluoridated water were lower than those in a matching town without fluoride, a later study failed to show differences. Ecological studies from the United States and Great Britain have, if anything, revealed a weak positive association between water fluoride concentration and hip fracture incidence. Two studies examining hip fracture rates before and after fluoridation yielded discordant results, and are complicated by underlying time trends in hip fracture incidence. Only two studies have attempted to examine the relation between water fluoride concentration and fracture risk at an individual level. In one of these, women in a high fluoride community had double the fracture risk of women in a low fluoride community. In the other, there was no relationship between years of fluoride exposure and incidence of spine or non-spine fractures. In conclusion, the epidemiological evidence relating water fluoridation to hip fracture is based upon ecological comparisons and is inconclusive. However, several studies suggest the possibility of a weak adverse effect, which warrants further exploration. Data on the relationship between fluoride intake and hip fracture risk at the individual level, and data relating fluoridation to bone mineral density are required. Until these become available, the burden of evidence suggesting that fluoridation might be a risk factor for hip fracture is weak and not sufficient to retard the progress of the water fluoridation programme.

Aged

Generalized osteoarthritis in women: pattern of joint involvement and approaches to definition for epidemiological studies.

OBJECTIVE: To ascertain whether clustering between joint sites in osteoarthritis (OA) is more common than would be expected simply from the rising prevalence of the disorder with age, and to explore a definition of generalized OA (GOA) by determining the pattern of joint group involvement, in a population sample of peri and postmenopausal women. METHODS: Radiographs of the hands, knees, and hips were obtained in a population sample of 702 women aged 45 to 64 years. Distal interphalangeal, proximal interphalangeal, carpometacarpal, knee, and hip OA were assessed using the Kellgren-Lawrence grading system. Logistic regression was used to test for overall clustering of OA between joint sites, and log linear models were used to study the patterns of association between different sites. RESULTS: Multiple involvement of the 5 joint groups studied occurred significantly more frequently than could be expected by chance alone (chi 2 = 52.3, df = 5, p < 0.001), and this clustering remained significant after age adjustment (chi 2 = 26.1, df = 5, p < 0.001). Thresholds could be defined for the number of involved joint groups that distinguished a polyarticular subset of OA. These thresholds varied with age and the radiographic cutoff at which OA was assigned. Thus, for grade 2+ disease, GOA could be defined by involvement of 2 or more joint groups at age 45-47 years, but required involvement of all 5 joint groups at age 60-64 years. Symmetry within joint groups was the most pronounced feature in the pattern of joint involvement in the sample as a whole, with associations between different joint groups being substantially weaker than those for symmetrical bilateral involvement of a particular joint. CONCLUSION: There is a clear tendency towards polyarticular OA among women aged 45-64 years. However, there is no single threshold number of joint sites that can be used to define GOA. The pattern of joint involvement in OA is primarily symmetrical, and this pattern strongly suggests a systemic etiology in this subset of postmenopausal women.

Arthrography

The art of reassurance.

Reassurance is an essential part of good medical practice. This article discusses the importance of reassurance as a therapeutic skill, and the specific techniques designed to improve its application.

Anxiety

Ig/EBP (C/EBP gamma) is a transdominant negative inhibitor of C/EBP family transcriptional activators.

Analysis of cDNA and genomic clones shows that the murine Ig/EBP (C/EBP gamma) gene encodes a small protein with a predicted molecular weight of 16.4 kDa which contains C/EBP family basic and leucine zipper domains but lacks the transcriptional activation domains present in C/EBP (C/EBP alpha) and NF-IL6 (C/EBP beta). In transfection assays Ig/EBP is neither an activator nor a repressor of transcription; however, Ig/EBP inhibits the transcriptional ability of NF-IL6 (C/EBP beta) and C/EBP (C/EBP alpha), acting as a transdominant negative regulator. Thus Ig/EBP resembles LIP, another negative regulator of the C/EBP family, in both structure and transcriptional activity. Of the three known C/EBP family inhibitors, Ig/EBP, LIP and CHOP-10, only Ig/EBP is ubiquitously expressed. Therefore, Ig/EBP may act as a general buffer for C/EBP activators in many cell types.

Animals

Vitamin C and risk of death from stroke and coronary heart disease in cohort of elderly people.

OBJECTIVES: To determine whether vitamin C status, as measured by dietary intake and plasma ascorbic acid concentration, is related to mortality from stroke and coronary heart disease in people aged 65 and over. DESIGN: A 20 year follow up study of a cohort of randomly selected elderly people living in the community who had taken part in the 1973-4 Department of Health and Social Security nutritional survey and for whom dietary and other data had been recorded. SETTING: Eight areas in Britain (five in England, two in Scotland, and one in Wales). SUBJECTS: 730 men and women who had completed a seven day dietary record and who had no history or symptoms of stroke, cerebral arteriosclerosis, or coronary heart disease when examined by a geriatrician in 1973-4. RESULTS: Mortality from stroke was highest in those with the lowest vitamin C status. Those in the highest third of the distribution of vitamin C intake had a relative risk of 0.5 (95% confidence interval 0.3 to 0.8) compared with those in the lowest third, after adjustment for age, sex, and established cardiovascular risk factors. The relation between vitamin C intake and stroke was independent of social class and other dietary variables. A similar gradient in risk was present for plasma ascorbic acid concentrations. No association was found between vitamin C status and risk of death from coronary heart disease. CONCLUSION: In elderly people vitamin C concentration, whether measured by dietary intake or plasma concentration of ascorbic acid, is strongly related to subsequent risk of death from stroke but not from coronary heart disease.

Aged

Childhood growth, physical activity, and peak bone mass in women.

Peak bone mass is an important determinant of the risk of osteoporotic fracture, and preventive strategies against osteoporosis require a clear understanding of the factors influencing bone gain in early life. We report a longitudinal study aiming to identify the relationships between childhood growth, lifestyle, and peak bone mass in women. One hundred and fifty-three women born in a British city during 1968-1969 were traced and studied in 1990. Data on their growth in childhood was obtained from linked birth and school health records; current bone mineral measurements were made by dual X-ray absorptiometry. There were statistically significant associations between weight at 1 year and BMC (but not BMD) at the lumbar spine (r = 0.32, p < 0.01) and femoral neck (r = 0.26, p < 0.01). These remained significant after adjusting for current weight. There were also strong relationships between childhood height measurements and adult BMC at the two skeletal sites. Physical activity was the major lifestyle determinant of BMD after allowing for body build. We conclude that infant growth and physical activity in childhood are important determinants of peak bone mass in women. Growth primarily determines the size of the skeletal envelope, and its trajectory is established by age 1 year. Activity, in contrast, modulates the mineral density within the skeletal envelope and may contribute to the consolidation of bone following the end of linear growth.

Absorptiometry, Photon

Cytokine induction of proliferation and expression of CDC2 and cyclin A in FDC-P1 myeloid hematopoietic progenitor cells: regulation of ubiquitous and cell cycle-dependent histone gene transcription factors.

To evaluate transcriptional mechanisms during cytokine induction of myeloid progenitor cell proliferation, we examined the expression and activity of transcription factors that control cell cycle-dependent histone genes in interleukin-3 (IL-3)-dependent FDC-P1 cells. Histone genes are transcriptionally upregulated in response to a series of cellular regulatory signals that mediate competency for cell cycle progression of the G1/S-phase transition. We therefore focused on factors that are functionally related to activity of the principal cell cycle regulatory element of the histone H4 promoter: CDC2, cyclin A, as well as RB- and IRF-related proteins. Comparisons were made with activities of ubiquitous transcription factors that influence a broad spectrum of promoters independent of proliferation or expression of tissue-specific phenotypic properties. Northern blot analysis indicates that cellular levels of cyclin A and CDC2 mRNAs increase when DNA synthesis and H4 gene expression are initiated, supporting involvement in cell cycle progression. Using gel-shift assays, incorporating factor-specific antibody and oligonucleotide competition controls, we define three sequential period following cytokine stimulation of FDC-P1 cells when selective upregulation of a subset of transcription factors is observed. In the initial period, the levels of SP1 and HiNF-P are moderately elevated; ATF, AP-1, and HiNF-M/IRF-2 are maximal during the second period; while E2F and HiNF-D, which contain cyclin A as a component, predominate during the third period, coinciding with maximal H4 gene expression and DNA synthesis. Differential regulation of H4 gene transcription factors following growth stimulation is consistent with a principal role of histone gene promoter elements in integrating cues from multiple signaling pathways that control cell cycle induction and progression. Regulation of transcription factors controlling histone gene promoter activity within the context of a staged cascade of responsiveness to cyclins and other physiological mediators of proliferation in FDC-P1 cells provides a paradigm for experimentally addressing interdependent cell cycle and cell growth parameters that are operative in hematopoietic stem cells.

Base Sequence

Asthma management and morbidity in Australian general practice: the relationship between patient and doctor estimates.

The aims of this study were to describe asthma management and morbidity in patients attending general practitioners in Australia, and to assess the relationship between patient reports and those of their general practitioner (GP). The sample comprised consecutive patients attending 46 general practitioners chosen at random in five regions of New South Wales, Australia. A total of 4538 patients were screened, 607 (13.4%) reported ever having diagnosed asthma, and the 501 who reported asthma in the previous 12 months completed a detailed questionnaire. Three hundred and thirty-four patients also had information about their asthma management recorded by their GP. The patient questionnaire asked about asthma symptoms, therapy, lung function measurement, and asthma-related morbidity. The GP questionnaire asked the doctor to record similar information about the patients. Two-thirds of the patients used regular inhaled beta 2-agonist medication, and one-half reported using preventive therapy. Only 24% owned a peak flow meter and 9% had a written plan of action for asthma attacks. Although preventive therapy and airway function assessment were more common in those with frequent symptoms (> 2-3 times per week), this group were still sub-optimally managed. In the matched sample (n = 334), doctors reported prescribing bronchodilator and preventive medication, measuring airway function and recommending peak flow meter use more often than suggested by patient-reported data. The study concludes that many patients do not attend for regular review, and that management remains sub-optimal, particularly in young adults. Data from patient surveys may underestimate clinical practice, as assessed from doctors' records. This should lead to patient-derived estimates of management being interpreted with caution in epidemiological studies. Further attention to patient understanding and compliance with prescribed asthma management advice is needed in order to better manage asthma in the community.

Adolescent

Osteoporosis.

Two complementary notions need to be considered in the definition of osteoporosis: a reduction in bone mineral density and the occurrence of fracture. Bone mineral density is an established determinant of the risk of future fracture, but current interventions are most usefully targeted before bone density has fallen to the levels at which fractures usually occur. Bone density may now be measured accurately and precisely, and the sensitivity and specificity of this technology for fracture risk prediction are high. It therefore seems reasonable to classify osteoporosis in terms of both a reduction in bone density and the occurrence of fracture. On this basis, a four point scale has recently been proposed by the World Health Organization: 1) normal, 2) low bone mass, 3) osteoporosis and 4) established osteoporosis. While it is likely that this diagnostic classification will change as experience of osteoporosis increases, it is important to have widely adopted guidelines of this type which act as a framework for further research.

Humans