How to assess drug efficacy in osteoporosis.
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Bone Density↗
Biomedical subjects
C Cooper
Publications and source records attributed to C Cooper.
Risk factors for hip fracture.
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Accidental Falls↗
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↗
Epidemiology of the rheumatic diseases.
Epidemiologic studies are important for both understanding and defining rheumatology practice. Controversy still exists over whether the incidence of rheumatoid arthritis is declining, and genetic studies indicate a diversity of HLA haplotypes in rheumatoid arthritis. Large longitudinal osteoarthritis studies have helped define diagnostic criteria and the role of obesity in disease progression. The negative association between osteoarthritis and osteoporosis at specific sites continues to be explored, and the value of long-term estrogen therapy in preventing bone loss has been examined. Both retrospective and prospective population studies have been used to describe the relationship between silicone gel breast implants and connective tissue disease. These and other studies have helped to define the important role of epidemiologic research in the understanding of rheumatic diseases.
Arthritis, Juvenile↗
AIDS-associated intussusception in young adults.
We have examined the changing demographics of adult intussusception and implicate human immunodeficiency virus (HIV)- and acquired immune deficiency syndrome (AIDS)-associated gastrointestinal pathology as risk factors for intussusception in young adults. The clinical index of suspicion for intussusception should be raised for an HIV-positive young adult with intermittent crampy abdominal pain. Over a 10-year period, eight cases of adult intussusception were diagnosed at our institution, and we reviewed the diagnostic computed tomography (CT) scans and records of these patients to correlate them with radiological studies, clinical history, surgical findings, laboratory studies, pathologic analysis, and outcome. Three of the eight patients with adult intussusception had AIDS, all diagnosed by CT scans. Their average age was 41 years, whereas average age of the non-HIV-associated patients was 63. These findings suggest that HIV- and AIDS-associated gastrointestinal pathology provide lead points for intussusception and are significant risk factors for intussusception in young adults. We reviewed the five previously reported cases of AIDS and intussusception and conclude that intussusception should be a diagnostic consideration in an HIV-positive young adult with abdominal complaints. It is clear that AIDS-associated intussusception is a real clinical problem and that CT is an effective method of diagnosing it.
Acquired Immunodeficiency Syndrome↗
Falls and major injuries are risk factors for thoracolumbar fractures: cognitive impairment and multiple injuries impede the detection of back pain and tenderness.
Risk factors for thoracolumbar fracture (TLF) and occurrence of back pain/tenderness detection (BPTD) in TLF patients have not been fully evaluated. Of 4142 blunt trauma patients directly admitted to a level I trauma center, 183 (4.4%) had a TLF. Risk factors for TLF (p < or = 0.05) were major non-TLF injuries (Abbreviated Injury Scale score > or = 3) and a fall mechanism of injury. Of 110 with TLF, Glasgow Coma Scale score (GCS) of 13 to 15, and no myelopathy, 34 (30.9%) had no BPTD; 7 of 34 (20.6%) required operative spinal stabilization. BPTD was lacking in 63% of patients with GCS scores of 13 to 14 compared to 22% of patients with GCS scores of 15 (p = 0.001). BPTD was decreased when major non-TLF injuries were present (63 vs. 91%) in the GCS score of 15 group (0.003), but similar in GCS score of 13 to 14 patients. In patients with GCS scores of 13 to 15, decreased BPTD is simultaneously related to both cognitive dysfunction and major injuries (p = 0.005). In conclusion, major injuries and falls are risks for TLF and cognitive deficit and major injury impedes BPTD in TLF. Thoracolumbar x-ray films should be carefully considered in patients with altered mentation or major injury.
Accidental Falls↗
Osteoporosis in rheumatological practice: questions to be answered.
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Absorptiometry, Photon↗
Rheumatoid arthritis, corticosteroid therapy and hip fracture.
OBJECTIVE: To identify the risk of hip fracture in patients with rheumatoid arthritis and those taking corticosteroids. METHODS: In a population based case-control study, we compared 300 consecutive patients with hip fracture aged 50 years and over from a defined district and 600 age and sex matched community controls. RESULTS: The risk of hip fracture was increased in patients with rheumatoid arthritis (odds ratio (OR) 2.1; 95% confidence interval (CI) 1.0 to 4.7) and those receiving corticosteroids (OR 2.7; 95% CI 1.2 to 5.8). The risk attributable to rheumatoid arthritis was markedly reduced by adjusting for functional impairment, while that for steroid use remained after adjusting for body mass index, smoking, alcohol, and functional status. CONCLUSIONS: Hip fracture risk is approximately doubled amongst patients with rheumatoid arthritis and among those taking steroids. These risk increases are, to some extent, independent of each other. In rheumatoid arthritis, the risk was most closely associated with functional impairment, whereas steroid use did not appear to be confounded by this variable.
Aged↗
Osteoarthritis of the hip joint and acetabular dysplasia in women.
OBJECTIVE: To investigate the suggestion that osteoarthritis (OA) of the hip joint is often caused by subclinical acetabular dysplasia among elderly British women. METHODS: We examined 393 hip joints from the radiographs of a sample of women aged 60-75 years undergoing intravenous urography. Acetabular dysplasia was assessed using measurements of the centre-edge (CE) angle and acetabular depth (AD), which are both reduced in this condition. OA was assessed using an overall grade based on the Kellgren and Lawrence system and by measurement of minimum joint space (MJS). RESULTS: MJS was the more repeatable measure of OA, and showed a strong correlation with overall grade (Spearman rank correlation coefficient rs = -0.61, p < 0.01). MJS was significantly negatively correlated with CE angle (Pearson correlation coefficient r = -0.25, p < 0.001) and AD (r = -0.11, p < 0.05). Consistent with these findings, there was a weak but significant positive correlation between overall grade of OA and one of the two measures (CE angle) of acetabular dysplasia. CONCLUSIONS: These results do not support the hypothesis that mild degrees of acetabular dysplasia account for a substantial proportion of hip OA in elderly women. Changes in hip joint geometry as a result of OA may be responsible for the weak negative association observed.
Aged↗
Low back pain in Hong Kong: prevalence and characteristics compared with Britain.
STUDY OBJECTIVE: To compare the prevalence of low back pain and associated disability in Hong Kong with that in Britain, and to explore whether differences could be explained by certain known risk factors. DESIGN: A cross sectional survey with information collected at interview. Findings were compared with those from an earlier survey in Britain. SETTING: Two housing blocks in Hong Kong. SUBJECTS: Altogether 288 men and 364 women aged 18 years or older, who were resident in the two housing blocks and agreed to interview (response rate = 80%). MAIN RESULTS: Thirty nine per cent (95% confidence interval (CI) 34%, 44%) of interviewees reported having had low back pain at some time, and 21% (95% CI 18%, 25%) had had low back pain in the past 12 months. After standardisation for age and sex, all of the back symptoms examined were substantially less common in Hong Kong than in Britain. The one year period prevalence of low back pain was associated with occupational lifting (in both sexes) and with tall stature (in men only). Subjects tended to carry out less heavy lifting at work and to be shorter than participants in the earlier British study but these differences did not completely explain their lower prevalence of back pain. CONCLUSIONS: The findings indicate a lower prevalence of back symptoms in Hong Kong than Britain that is partly explained by differences in stature and occupational lifting. In addition, Hong Kong people may have a higher threshold for reporting symptoms, or they may differ in their exposure to other, unrecognised risk factors.
Adolescent↗
Manual handling activities and risk of low back pain in nurses.
OBJECTIVE: To investigate the risk factors for low back pain in hospital nurses, with particular emphasis on the role of specific nursing activities. METHODS: A cross sectional survey of 2405 nurses employed by a group of teaching hospitals was carried out. Self administered questionnaires were used to collect information about occupational activities, non-occupational risk factors for back symptoms, and history of low back pain. RESULTS: The overall response rate was 69%. Among 1616 women, the lifetime prevalence of back pain was 60% and the one year period prevalence 45%. 10% had been absent from work because of back pain for a cumulative period exceeding four weeks. Rates in men were generally similar to those in women. In women back pain during the previous 12 months was weakly associated with height, and was significantly more common in those who reported frequent non-musculoskeletal symptoms such as headache and low mood. After adjustment for height and non-musculoskeletal symptoms, significant associations were found with frequency of manually moving patients around on the bed, manually transferring patients between bed and chair, and manually lifting patients from the floor. In contrast, no clear increase in risk was found in relation to transfer of patients with canvas and poles, manually lifting patients in and out of the bath, or lifting patients with mechanical aids. Confirmation of these findings is now being sought in a prospective study of the same population. CONCLUSIONS: This study confirms that low back pain is highly prevalent among nurses and is associated with a high level of sickness absence. People who often report non-musculoskeletal symptoms were significantly more likely to report low back pain. Specific manual handling tasks were associated with an increased risk of back pain; however, no such association was found with mechanised patient transfers.
Adult↗
Biliary tract: three-dimensional helical CT without cholangiographic contrast material.
Bile duct anatomy depicted with a three-dimensional (3D) model developed with helical computed tomography (CT) data was compared with cholangiographic depiction. The ductal system was completely displayed from all angles in four of six patients, as well as the stricture and length of bile duct between strictures and the bifurcation in five of six cases. 3D rendering can depict preoperative ductal anatomy.
Adult↗
Conspicuity of hepatic metastases on helical CT: effect of different time delays between contrast administration and scanning.
OBJECTIVE: The purpose of this study was to compare two time delays between injection of contrast material and helical CT scanning to determine relative conspicuity of hepatic metastases. SUBJECTS AND METHODS: Twenty-five patients with hepatic metastases were examined with helical CT. The first imaging phase was initiated at 50 sec and the second 75 sec after the start of contrast material injection (3 ml/sec, 150 ml). Differences in lesion and liver attenuation were measured quantitatively. Four radiologists used a 5-point scale to assess lesion conspicuity subjectively. RESULTS: Mean differences in enhancement between liver and lesion were 41 H during the first phase and 59 H for the second phase (p = .0001). Radiologists' conspicuity score averaged 2.4 for lesions in the first phase versus 3.3 for lesions in the second phase (p = .0001). In 56 (88%) of 64 lesions, objective measurements showed greater enhancement of lesions during the later phase. Radiologists found 60 (94%) of 64 lesions to be more conspicuous on these later images. CONCLUSION: Our results show that conspicuity of hepatic metastases on helical CT scans is better with a 75-sec scan delay between contrast administration and scanning than with a 50-sec scan delay. The longer delay time should be used when scanning is used to detect metastases.
Adult↗
Optimal contrast enhancement of the liver using helical (spiral) CT: value of SmartPrep.
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Aortography↗
Diagnosis of aortic dissection: value of helical CT with multiplanar reformation and three-dimensional rendering.
OBJECTIVE: Twenty-three patients with suspected aortic dissection were evaluated in this preliminary study of helical CT to determine the usefulness of axial sections, multiplanar reformation, and three-dimensional (3D) rendering in assessing the presence of dissection and the extent of intimal flap. MATERIALS AND METHODS: Patients were referred for helical CT scanning because of chest pain or an abnormal chest radiograph. Scans were performed during bolus injection of nonionic contrast material at 2.0-2.5 ml/sec using a mean scan delay of 47 sec. Axial scans with 5-mm collimation were obtained in all patients. They extended from the great vessels to the distal thoracic aorta just above the hiatus. Delayed nonhelical sections were obtained through the upper abdomen. Multiplanar reformations and 3D models were reconstructed from the helical data in 13 patients and were compared to axial sections in 7 patients who proved to have documented dissection. The efficacy of CT was determined using surgery, angiography, or clinical outcome to establish the diagnosis. RESULTS: Of the 23 patients studied, axial sections resulted in 15 true-negative, 7 true-positive, and 1 false-positive interpretation. In three of seven patients with dissection, it was difficult to determine the extent of the intimal flap on axial sections; multiplanar reformation or 3D views clarified the relevant anatomy in all 3 cases. Among the 3D display methods, ray-sum projection views were superior to surface model or maximum-intensity-projection views. CONCLUSION: If studies of larger numbers of patients confirm our preliminary findings, multiplanar reformation and 3D rendering of helical CT scans will be a valuable addition to axial display of CT studies used to detect aortic dissection and to determine the extent of the intimal flap.
Adult↗