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Biomedical subjects

B Lees

Publications and source records attributed to B Lees.

At least 19 recordsLinked to original sources

DXA longitudinal quality control: a comparison of inbuilt quality assurance, visual inspection, multi-rule Shewhart charts and Cusum analysis.

The performance of dual-energy X-ray absorptiometry (DXA) instruments can be monitored using various quality control (QC) procedures. It has not been established which of these is most appropriate. The aim of this study was to determine which of four QC procedures is the best to use for longitudinal monitoring. Eighteen centres with DXA instruments scanned an aluminium spine phantom weekly for up to 16 months, and the bone mineral density data were used for the QC procedures. The methods investigated were the instrument's inbuilt quality assurance (QA) procedure, visual inspection, multi-rule Shewhart control charts, and Cusum analysis using a truncated-V mask. True and false positive fractions (TPF and FPF) of each method were calculated, including those for a range of action levels for the Shewhart charts and dimensions of the Cusum mask. For Shewhart, the action levels giving the most desirable TPF and FPF were whole multiples of the standard deviation (SD). For Cusum, the most desirable mask dimensions were 3.6 SD for the total height of the vertical section and 0.9 SD per data point for the gradient of the wings. Predictive power of each method as a means of fault detection was decided by the number of faults detected out of a total of 8 non-mechanical faults subsequently diagnosed. The inbuilt QA detected 2, visual inspection 7, Shewhart chart 7 and Cusum analysis 7. The FPFs were: visual inspection 0.09, Shewhart 0.04, Cusum 0.08. At these levels of FPF, the average time in days (range) from onset of a fault to detection was 39 (6-82) for visual inspection, 39 (4-116) for Shewhart and 21 (1-49) for Cusum. All three "phantom" methods are excellent for DXA QC, with modified Cusum analysis being the most effective. The inbuilt QA appears of little use on its own for longitudinal QC.

Absorptiometry, Photon

Evaluation of the European Spine Phantom in a multi-centre clinical trial.

The European Spine Phantom (ESP) has recently been developed as a universal standard for instruments measuring bone density. The ESP is composed of three semi-anthropomorphic hydroxyapatite vertebrae of varying densities surrounded by soft tissue equivalent plastic designed to resemble human bone and soft tissue when scanned on bone densitometers. In multi-centre studies it is particularly important to verify that each participating bone densitometer is performing in a stable and linear fashion. The aim of this study was to evaluate the ESP within the context of a multi-centre clinical trial. Eighteen centres in the UK and Canada with dual-energy X-ray absorptiometry (DXA) instruments (Lunar DPX, DPX-alpha and DPX-L) participated in the study. The ESP was scanned 10 times on each instrument without repositioning using standardized protocols. The precision of the bone mineral density (BMD) measurements (LI-3) expressed as a coefficient of variation ranged from 0.4% to 1.1% (mean 0.7%). The mean BMD of each instrument was expressed as a percentage difference from the overall mean and ranged from -1.33% to 1.33%. Linear regression analysis showed that all instruments behaved in a linear fashion across the range of densities with correlation coefficients all > or = 0.999 and standard errors of the estimate < 1.5% of the mean BMD ESP value. The data from this study demonstrate that the ESP is a useful phantom for assessing the linearity, stability and differences between DXA instruments from one manufacturer.

Absorptiometry, Photon

Role of oral pamidronate in preventing bone loss in postmenopausal women.

We have performed a 2-year prospective double-masked study to determine whether the bisphosphonate pamidronate can prevent bone loss in postmenopausal women and its optimal dosage regimen. One hundred and twenty-one such women (mean +/- SD age 57.6 +/- 3.4 years; mean +/- SD time since menopause 7.5 +/- 3.5 years) were randomized to receive either oral pamidronate (300 mg/day) for 4 weeks every 4 months (group A), oral pamidronate (150 mg/day) for 4 weeks every 2 months (group B) or identical placebo capsules (group C). Bone mineral density (BMD) measurements at the lumbar spine and proximal femur were performed at baseline and at 6-month intervals for 2 years using dual-energy X-ray absorptiometry. BMD at the lumbar spine (L2-4) increased significantly in groups A and B after 2 years of treatment (mean +/- SD 2.8 +/- 2.1% and 3.0 +/- 2.9% respectively, both p < 0.001) but decreased in the placebo group (-1.6 +/- 3.1%, p < 0.01). Identical results were seen for BMD at the femoral neck, which increased significantly in groups A and B after 2 years of treatment (1.2 +/- 2.3% and 1.3 +/- 2.9% respectively, both p < 0.05) but decreased in the placebo group (-1.9 +/- 3.9%, p < 0.05). There were significant differences over 2 years between the groups at all anatomical sites (lumbar spine, femoral neck and trochanteric region, all p < 0.001; Ward's triangle, p < 0.01). However, there were no significant differences between groups A and B, suggesting that the two treatment regimens were equally effective in conserving BMD. There were, however, marked differences in tolerability between the two treatment regimens: 13 women (34%) in group A withdrew from the study because of side-effects, but only 5 women (12%) in group B, which was comparable with placebo. These data demonstrate that intermittent oral pamidronate will prevent bone loss from the lumbar spine and proximal femur of postmenopausal women, and that the more frequent but lower dose regimen is well tolerated.

Absorptiometry, Photon

Intranasal salmon calcitonin for the prevention and treatment of postmenopausal osteoporosis.

In a randomized, double-blind, placebo-controlled trial, we have studied the effects of intranasal salmon calcitonin (SCT) on bone mineral density (BMD) and biochemical markers of bone turnover over a period of 2 years. Our study comprised 117 Caucasian postmenopausal women, otherwise healthy apart from reduced bone density. They received either intranasal synthetic SCT (200 IU either three times weekly or daily) or placebo. Compared with placebo, daily intranasal calcitonin resulted in no significant bone loss in the lumbar spine, as assessed by dual photon absorptiometry, over the 2-year study period (P < 0.02). In this group, women more than 5 years postmenopause, with the lowest baseline bone mass, showed the greatest response to this treatment, with a total increase placebo in lumbar spine BMD of 3.1%. Significant spinal bone loss (P < 0.005) occurred in women receiving either placebo or thrice-weekly calcitonin. Although the rates of bone loss in the proximal femur were not significantly different in the three groups, there were differences over time. Whereas bone loss in the daily calcitonin group was insignificant, women who received placebo or thrice-weekly calcitonin experienced significant bone loss (P < 0. 001). No significant changes in biochemical markers were observed in any group. Therapy was well tolerated and there were no significant treatment-related adverse events. We conclude that intranasal SCT 200 IU daily is effective and safe for the prevention of bone loss in postmenopausal women with reduced bone mass.

Administration, Intranasal

Measuring body fat.

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Absorptiometry, Photon

Changes in bone density in women starting hormone replacement therapy compared with those in women already established on hormone replacement therapy.

It is well established that hormone replacement therapy (HRT) will prevent postmenopausal loss of bone. However, it is not known to what extent HRT will continue to affect bone mineral density (BMD) in women established on HRT compared with those commencing treatment. We recruited 48 healthy early postmenopausal women into a prospective, comparative study. Twenty-nine women had never taken HRT (group A) whilst 19 women were already taking HRT (group B) (conjugated equine oestrogens, 0.625 mg daily; mean (+/- SD) years of use 2.2 (1.5) years). All of the women were started on, or switched to, micronized 17 beta-oestradiol (2 mg/day) continuously with dydrogesterone (10 mg/day) for the first 14 days of each cycle. BMD measurements were performed at the lumbar spine and proximal femur using dual-energy X-ray absorptiometry (DXA) at baseline and after 12 and 24 months of treatment. Group A showed a significantly greater increase in lumbar spine BMD after 12 months (mean +/- SD) = 5.3 (4.6)%) compared with group B (mean +/- SD) = 2.1 (2.1)%) and 24 months of treatment (group A, mean (+/- SD) = 6.4 (5.2)%; group B, mean (+/- SD) = 2.3 (2.6)%; both p < 0.01) and 24 months of treatment (r = -0.05). These data demonstrate that HRT has the greatest effect on BMD when it is first administered, especially in those women with low BMD, but improvements may still be observed in women continuing HRT in the longer term.

Adult

Relationships between insulin metabolism, serum lipid profile, body fat distribution and blood pressure in healthy men.

Insulin resistance and hyperinsulinaemia may be important in a cluster of coronary heart disease-related metabolic disturbances known as the insulin resistance syndrome. Whether the relationships between insulin and other features of the syndrome are independent of the amount and distribution of body fat is uncertain. We have investigated these relationships in 103 healthy males, using dual-energy X-ray absorptiometry to measure body fat directly. Volunteers underwent an intravenous glucose tolerance test (IVGTT), from which insulin sensitivity, secretion and elimination were determined by mathematical modelling analysis. Independently of adiposity and body fat distribution, serum triglyceride concentration was correlated with fasting C-peptide concentration and second-phase intravenous glucose tolerance test insulin concentration (r = 0.42, P < 0.001; r = 0.28, P < 0.05). High density lipoprotein subfraction 2 (HDL2) cholesterol was correlated with fasting C-peptide, first-phase IVGTT insulin concentration, and the hepatic insulin throughout index (r = -0.15 -0.20, -0. 20 respectively, all P < 0.05). The association of HDL2 cholesterol with the hepatic throughput index was additionally independent of serum triglyceride concentration (r = -0.18, P < 0.05). Our results suggest that relative hyperinsulinaemia leads to elevated triglyceride concentration, independently of body fat mass and distribution. Furthermore, the independent association of HDL2 cholesterol with hepatic insulin throughput confirms that hepatic insulin processing may may directly influence lipoprotein metabolism.

Absorptiometry, Photon

Body fat distribution, rather than overall adiposity, influences serum lipids and lipoproteins in healthy men independently of age.

PURPOSE: We investigated the relationships between the amount and distribution of body fat and fasting serum lipids and lipoproteins to explore whether coronary artery disease (CAD) risk may be mediated through effects on the serum lipid profile. PATIENTS AND METHODS: We determined serum total cholesterol and triglyceride, low-density lipoprotein cholesterol, high-density lipoprotein (HDL) cholesterol, and HDL subfractions 2 and 3 in 103 healthy men, aged 21 to 77 years (mean 48.7). The amount and distribution of fat were determined directly by dual energy X-ray absorptiometry. Adiposity was determined as the ratio between total body fat tissue and total body lean tissue, while fat distribution was taken as the ratio between the mass of fat tissue in the android (central) and gynoid (hip and thigh) regions. RESULTS: Univariate analysis showed both adiposity and fat distribution to be correlated with total serum cholesterol and triglyceride concentrations (adiposity r = .20, .21; both P < 0.05: fat distribution r = .25, .38; P < 0.05, P < 0.001, respectively). Fat distribution was also negatively correlated with HDL2 cholesterol (r = -.20, P < 0.05). In multiple linear regression analysis, neither age nor adiposity was significantly correlated with any serum lipid or lipoprotein concentration, while increasing android-to-gynoid ratio was independently associated with elevated total serum triglyceride (r = .40, P < 0.01) and decreased HDL2 (r = -.25, P < 0.05) concentrations. CONCLUSIONS: The association of both age and overall adiposity with the fasting serum lipid profile are mediated via their correlations with body fat distribution. In men, the distribution, rather than the amount, of body fat is related to adverse changes in serum lipids and lipoproteins, and hence potentially to increased CAD risk.

Absorptiometry, Photon

Gonadotropin-releasing hormone analogue (goserelin) plus hormone replacement therapy for the treatment of endometriosis: a randomized controlled trial.

OBJECTIVE: To determine whether treatment of endometriosis with a GnRH analogue (GnRH-a; goserelin) combined with continuous estrogen and progestogen hormone replacement therapy (HRT) would prevent the hypoestrogenic effects, including loss of bone density, while maintaining efficacy for treatment of endometriosis. DESIGN: Randomized controlled trial. PATIENTS: Fifty premenopausal women with laparoscopically diagnosed endometriosis (revised American Fertility Score for endometriosis implants equal to four or greater) and significant symptoms of dysmenorrhoea, dyspareunia, and other pelvic pain. INTERVENTION: Patients were randomized to receive either goserelin alone, 3.6 mg SC depot every 4 weeks for 24 weeks, or goserelin, 3.6 mg SC depot every 4 weeks for 24 weeks, plus HRT (25 micrograms transdermal 17 beta E2 daily and 5 mg medroxyprogesterone acetate orally daily) for 20 weeks commencing with the second goserelin injection. RESULTS: There was a significant reduction in the extent of pelvic endometriosis in both groups, with no difference between the groups. Both groups experienced an improvement in symptoms and signs, again with no difference between groups. Hypoestrogenic side effects of hot flushes and loss of libido were significantly less in the group that received HRT. The amount of bone mineral density loss was significantly less in the HRT group at the lumbar spine, although it was not prevented completely. CONCLUSION: The addition of HRT to GnRH-a for the treatment of endometriosis did not reduce the efficacy of treatment, and adverse hypoestrogenic effects were decreased, although not abolished.

Adult

Insulin resistance syndrome in postmenopausal women with cardiological syndrome X.

OBJECTIVE: To determine whether postmenopausal women with cardiological syndrome X (chest pain and abnormal exercise electrocardiogram despite normal coronary angiography) exhibit disturbances in the full range of proposed components of the putative "insulin resistance syndrome". PATIENTS AND METHODS: 20 postmenopausal women with syndrome X and 20 healthy controls each underwent measurement of insulin resistance (by minimal model analysis of the intravenous glucose tolerance test), lipid, lipoprotein, and apolipoprotein concentrations, a range of haemostatic variables, serum uric acid concentration, and centrality of body fat distribution (by dual energy x ray absorptiometry). RESULTS: Women with syndrome X had higher fasting triglyceride concentrations than controls (median: 1.60 v 1.02 mmol/l, P < 0.05). Concentrations of high density lipoprotein cholesterol were lower (1.33 v 1.61 mmol/l, P < 0.05) as were those of the high density lipoprotein apolipoproteins AI and AII. Insulin and C peptide responses to the intravenous glucose tolerance test were higher (27.6 v 19.8 microU/ml/min, P < 0.01; 101 v 72 pmol/ml/min, P < 0.05, respectively), and insulin sensitivity was lower (1.89 v 3.09 min/microU/ml, P < 0.05). There were, however, no significant differences between other proposed components of the insulin resistance syndrome (blood pressure, glucose tolerance, proportion of central body fat, serum uric acid concentration, and plasminogen activator inhibitor-1 activity). Antithrombin III activity was higher in women with syndrome X (121 v 113%, P < 0.01). CONCLUSIONS: Women with syndrome X tend to be insulin resistant and have lipid and lipoprotein abnormalities, but do not exhibit all characteristics of the insulin resistance syndrome. Such variation in correlated risk factors is consistent with underlying heterogeneity in the insulin resistance syndrome and cardiological syndrome X.

Aged

Long-term effects of transdermal and oral hormone replacement therapy on postmenopausal bone loss.

Transdermal hormone replacement therapy (HRT) is now an accepted form of treatment, but the long-term skeletal effects have not been assessed. Sixty-six early postmenopausal women were randomized to receive either transdermal HRT (continuous 17 beta-oestradiol 0.05 mg/day, with 0.25 mg/day of norethisterone acetate added for 14 days of each 28-day cycle) or oral HRT (continuous conjugated equine oestrogens 0.625 mg/day, with 0.15 mg/day dl-norgestrel added for 12 days of each 28-day cycle). Treatment was given for 3 years and 30 matched untreated women were studied concurrently as a control group. Bone density was measured in the lumbar spine and proximal femur by dual-photon absorptiometry at 6-monthly intervals. Bone turnover was assessed by measurement of biochemical markers. At 3 years bone density had declined by 4% in the lumbar spine and by more than 5% in the femoral neck in the untreated group. By comparison bone density increased in both treatment groups at both sites (p < 0.001 vs. untreated) and biochemical measurements indicated a significant reduction in bone turnover. There were no significant differences between the treatment groups. Twelve per cent of women on transdermal or oral treatments lost a significant amount of bone from the femoral neck by 3 years despite adequate compliance. Women taking therapy primarily for hip fracture prevention may require a follow-up bone density measurement to establish the efficacy of treatment.

Administration, Cutaneous

Bone density and endometriosis.

To establish whether there is evidence of low bone density in women with endometriosis, we compared bone density between 48 women with laparoscopically proven endometriosis and 48 age-matched normal controls. Bone density of the lumbar spine (L2-4), proximal femur (femoral neck, Ward's triangle, and trochanteric region), and total body were measured by dual energy roentgenogram absorptiometry. After adjusting for physical and lifestyle differences, bone density was not significantly different between the groups in any site. Bone density measurements were not related to the severity of endometriosis. These results do not confirm evidence of low bone density in women with endometriosis.

Absorptiometry, Photon

Effect of degenerative spinal and aortic calcification on bone density measurements in post-menopausal women: links between osteoporosis and cardiovascular disease?

The effect of spinal degenerative changes and aortic calcification on bone mineral density measurements was studied in 115 healthy early post-menopausal women. Lateral lumbar spine radiographs and quantitative computer tomography images were used to determine the presence and severity of aortic calcification and degenerative changes in the lumbar spine. Women with spinal degenerative calcification had higher spine bone density when measured by dual photon absorptiometry compared to those without calcification (P < 0.01), but this was not reflected by the quantitative computer tomography or the proximal femur bone densities, suggesting that spinal calcification artefactually increases spinal bone density when measured by dual photon techniques. Women with aortic calcification had significantly lower quantitative computer tomography and proximal femur bone density compared to those without calcification (both P < 0.05). These women may be at increased risk for both osteoporosis and cardiovascular disease, suggesting a common aetiological factor such as oestrogen deficiency.

Aortic Diseases

Differences in proximal femur bone density over two centuries.

The incidence of osteoporotic hip fractures in northern Europe has been increasing over the past few decades faster than the rate adjusted for increased life expectancy. One important factor that determines osteoporotic fracture risk is bone density. The restoration of a London church, during which skeletal material dating from 1729 to 1852 was recovered, gave us the opportunity to compare the rate of bone loss in the femora of these samples with that of present-day women. The rate of bone loss, as judged by dual energy X-ray absorptiometry, was significantly greater in modern-day women than in the women from two centuries ago, both pre-menopausally (p < 0.05) and post-menopausally (p < 0.01). The difference in bone loss in the Ward's triangle region between the Spitalfields samples and present-day women remained even when the assumed age at menopause was increased to 48 years or decreased to 42 years. The results suggest that differences in rates of bone loss over two centuries may partly account for the increasing incidence of hip fracture in modern-day women. Reasons for these differences are unclear, but one factor may be a lower degree of physical activity in present-day women.

Adolescent

Preliminary evaluation of a new ultrasound bone densitometer.

A new ultrasound bone densitometer has been developed that measures ultrasonic properties of the os calcis, namely, the speed of sound (SOS), broadband ultrasound attenuation (BUA), and a proprietary factor derived from SOS and BUA, termed "stiffness." Short-term precision of ultrasound measurements was 1.4% for BUA, 0.2% for SOS, and 1.5% for stiffness in healthy women, and 1.1% for BUA, 0.1% for SOS, and 1.5% for stiffness in osteopenic women. One hundred seven women underwent measurements by ultrasound, together with dual energy X-ray absorptiometry (DXA) bone mineral density (BMD) measurements of the lumbar spine and proximal femur. Correlations between SOS, BUA, and stiffness measurements and DXA BMD measurements were all highly significant (P < 0.001) with r values varying from 0.54 to 0.67. BUA, SOS, and stiffness measurements were all significantly different between normal and osteopenic women even after adjusting for age, height, and weight (P < 0.05, P < 0.001, and P < 0.01, respectively). These results demonstrate that this ultrasound system measures ultrasonic properties of the os calcis with good precision, the measurements correlate moderately well with DXA BMD measurements and they can differentiate between normals and those with osteopenia.

Absorptiometry, Photon

A randomized comparative study of the metabolic effects of two regimens of gestrinone in the treatment of endometriosis.

OBJECTIVE: To study some of the metabolic effects of oral gestrinone on plasma lipoprotein risk markers for cardiovascular disease and on bone density, a risk marker for osteoporosis. DESIGN: Randomized double-blind study. SETTING: All patients were referred to Gynaecology Clinic of Royal Free Hospital Medical School. PATIENTS: Twenty premenopausal women with laparoscopically confirmed endometriosis. INTERVENTIONS: Subjects were randomized in a double-blind fashion to receive either 1.25 mg or 2.5 mg gestrinone two times per week for 6 months. MAIN OUTCOME MEASURE: Laparoscopy was performed before treatment, and clinical responses were determined by second laparoscopy after 6 months. Plasma lipid and bone density measurements during and after therapy were compared with baseline. RESULT: Median total endometriosis scores decreased from 7.5 to 1.0 in the 1.25-mg group and from 7.0 to 0 in the 2.5-mg group. There were no significant between-group differences in endometriosis scores. At both doses, bone density in the spine and the proximal femur was conserved, but plasma concentrations of low-density lipoproteins rose by 13% and those of high-density lipoproteins fell by 40%. CONCLUSIONS: Reducing the dose of gestrinone to 1.25 mg appeared to maintain the therapeutic effectiveness of this treatment but was still associated with potentially unfavorable effects on lipids and lipoproteins.

Adult