The impact of obesity on the relationship between epicardial adipose tissue, left ventricular mass and coronary microvascular function.

PURPOSE: Epicardial adipose tissue (EAT) has been linked to coronary artery disease (CAD) and coronary microvascular dysfunction. However, its injurious effect may also impact the underlying myocardium. This study aimed to determine the impact of obesity on the quantitative relationship between left ventricular mass (LVM), EAT and coronary microvascular function. METHODS: A total of 208 (94 men, 45 %) patients evaluated for CAD but free of coronary obstructions underwent quantitative [(15)O]H2O hybrid positron emission tomography (PET)/CT imaging. Coronary microvascular resistance (CMVR) was calculated as the ratio of mean arterial pressure to hyperaemic myocardial blood flow. RESULTS: Obese patients [body mass index (BMI) > 25, n = 133, 64 % of total] had more EAT (125.3 ± 47.6 vs 93.5 ± 42.1 cc, p < 0.001), a higher LVM (130.1 ± 30.4 vs 114.2 ± 29.3 g, p < 0.001) and an increased CMVR (26.6 ± 9.1 vs 22.3 ± 8.6 mmHg×ml(-1)×min(-1)×g(-1), p < 0.01) as compared to nonobese patients. Male gender (ß = 40.7, p < 0.001), BMI (ß = 1.61, p < 0.001), smoking (ß = 6.29, p = 0.03) and EAT volume (ß = 0.10, p < 0.01) were identified as independent predictors of LVM. When grouped according to BMI status, EAT was only independently associated with LVM in nonobese patients. LVM, hypercholesterolaemia and coronary artery calcium score were independent predictors of CMVR. CONCLUSION: EAT volume is associated with LVM independently of BMI and might therefore be a better predictor of cardiovascular risk than BMI. However, EAT volume was not related to coronary microvascular function after adjustments for LVM and traditional risk factors.

Ablation of colorectal liver metastases by irreversible electroporation: results of the COLDFIRE-I ablate-and-resect study.

OBJECTIVES: Irreversible electroporation (IRE) is a new ablation technique that relies on high-voltage electrical pulses. This clinical study evaluates the pathological response of colorectal liver metastases (CRLM) treated with IRE and the clinical safety and feasibility. METHODS: Ten patients with resectable CRLM were included. During laparotomy, the metastases were treated with IRE and resected 60 min later. Safety and feasibility were assessed based on adverse events, laboratory values, technical success and intra-operative ultrasound findings. Tissue response was assessed using triphenyl tetrazolium chloride (TTC) vitality staining and (immuno)histochemical stainings (HE, complement-3d and caspase-3). RESULTS: Ten lesions with a mean diameter of 2.4 cm were successfully electroporated and resected, on average, 84 min later (range 51-153 min). One minor transient cardiac arrhythmia occurred during IRE. Ultrasound showed a sharply demarcated hypoechoic ablation zone around the tumour. TTC showed avitality of all lesions, covering the complete tumour in 8/10 lesions. Although immunohistochemistry proved heterogeneous and difficult to interpret within the tumours, it confirmed irreversible cell damage in the tumour-free margin of all specimens. CONCLUSIONS: This ablate-and-resect study demonstrated avitality caused by IRE of CRLM in humans. Further characterisation of tissue- and tumour-specific electrical properties is warranted to improve ablation protocols for maximised tissue ablation. KEY POINTS: • Irreversible electroporation induces cell death in colorectal liver metastases within 1 h. • The ablation zone shows a sharp demarcation between avital and vital tissue. • Apoptosis is involved in cell death of colorectal liver metastases after IRE. • Effects of IRE can be monitored real-time using intraoperative ultrasound. • Local electrical heterogeneities of tumour tissue may require tumour-specific ablation protocols.

Transcatheter CT arterial portography and CT hepatic arteriography for liver tumor visualization during percutaneous ablation.

PURPOSE: To evaluate the feasibility of combining transcatheter computed tomography (CT) arterial portography or transcatheter CT hepatic arteriography with percutaneous liver ablation for optimized and repeated tumor exposure. MATERIALS AND METHODS: Study participants were 20 patients (13 men and 7 women; mean age, 59.4 y; range, 40-76 y) with unresectable liver-only malignancies--14 with colorectal liver metastases (29 lesions), 5 with hepatocellular carcinoma (7 lesions), and 1 with intrahepatic cholangiocarcinoma (2 lesions)--that were obscure on nonenhanced CT. A catheter was placed within the superior mesenteric artery (CT arterial portography) or in the hepatic artery (CT hepatic arteriography). CT arterial portography or CT hepatic arteriography was repeatedly performed after injecting 30-60 mL 1:2 diluted contrast material to plan, guide, and evaluate ablation. The operator confidence levels and the liver-to-lesion attenuation differences were assessed as well as needle-to-target mismatch distance, technical success, and technique effectiveness after 3 months. RESULTS: Technical success rate was 100%; there were no major complications. Compared with conventional unenhanced CT, operator confidence increased significantly for CT arterial portography or CT hepatic arteriography cases (P < .001). The liver-to-lesion attenuation differences between unenhanced CT, contrast-enhanced CT, and CT arterial portography or CT hepatic arteriography were statistically significant (mean attenuation difference, 5 HU vs 28 HU vs 70 HU; P < .001). Mean needle-to-target mismatch distance was 2.4 mm ± 1.2 (range, 0-12.0 mm). Primary technique effectiveness at 3 months was 87% (33 of 38 lesions). CONCLUSIONS: In patients with technically unresectable liver-only malignancies, single-session CT arterial portography-guided or CT hepatic arteriography-guided percutaneous tumor ablation enables repeated contrast-enhanced imaging and real-time contrast-enhanced CT fluoroscopy and improves lesion conspicuity.

Anaesthetic management during open and percutaneous irreversible electroporation.

BACKGROUND: Irreversible electroporation (IRE) is a novel tumour ablation technique involving repetitive application of electrical energy around a tumour. The use of pulsed electrical gradients carries a risk of cardiac arrhythmias, severe muscle contractions, and seizures. We aimed to identify IRE-related risks and the appropriate precautions for anaesthetic management. METHODS: All patients who were treated with IRE were prospectively included. Exclusion criteria were arrhythmias, congestive heart failure, active coronary artery disease, and epilepsy. All procedures were performed under general anaesthesia with complete muscle relaxation during ECG-synchronized pulsing. Adverse events, cardiovascular effects, blood samples, cerebral activity, and post-procedural pain were analysed. RESULTS: Twenty-eight patients underwent 30 IRE sessions for tumours in the liver, pancreas, kidney, and lesser pelvis. No major adverse events occurred during IRE. Median systolic and diastolic blood pressure increased by 44 mm Hg (range -7 to 108 mm Hg) and 19 mm Hg (range 1-50 mm Hg), respectively. Two transient minor cardiac arrhythmias without haemodynamic consequences were observed. Muscle contractions were mild and IRE caused no reactive brain activity on a simplified EEG. Pain in the first 24 h after percutaneous IRE was generally mild, but higher pain scores were reported after pancreatic treatment (mean VAS score 3; range 0-9). CONCLUSIONS: Side-effects during IRE on tumours in the liver, pancreas, kidney, and lesser pelvis seem mild and manageable when current recommendations for anaesthesia management, including deep muscle relaxation and ECG synchronized pulsing, are followed. Electrical pulses do not seem to cause reactive cerebral activity and evidence for pre-existing atrial fibrillation as an absolute contra-indication for IRE is questionable.

Magnetic resonance imaging in the evaluation of (deep infiltrating) endometriosis: the value of diffusion-weighted imaging.

PURPOSE: To assess the value of magnetic resonance (MR)diffusion-weighted imaging (DWI) in the evaluation of deep infiltrating endometriosis (DIE). MATERIALS AND METHODS: In a prospective single-center study, DWI was added to the standard MRI protocol in 56 consecutive patients with known or suspected endometriosis. Endometriotic lesions as well as (functional) ovarian cysts were analyzed for location, size, and signal intensity on T1, T2, and DWI. Apparent diffusion coefficient (ADC) values were calculated using b-values of 50, 400, 800,and 1200 s/mm(2). Statistical analysis included the Spearman correlation coefficient, Mann-Whitney U, and Kruskal-Wallis tests. RESULTS: A total of 110 lesions (62 endometrial cysts and 48 DIE) were detected, 60 of which were large enough to analyze. Mean ADC values of endometrial cysts and functional ovarian cysts were 1.10 x 10(-3)/mm(2)/s and 2.14 x 10(-3)/mm(2)/s, respectively. Mean ADC values of DIE retrocervical, infiltrating the colon, and bladder were 0.70 x 10(-3)/mm(2)/s, 0.77 x 10(-3)/mm(2)/s, and 0.79 x 10(-3)/mm(2)/s, respectively. ADC values of DIE did not show a significant difference between varying pelvic locations (P = 0.63). CONCLUSION: Results of our study suggest that ADC values of DIE are consistently low, without significant difference between pelvic locations.

Magnetic resonance imaging in the evaluation of (deep infiltrating) endometriosis: the value of diffusion-weighted imaging.

PURPOSE: To assess the value of magnetic resonance (MR) diffusion-weighted imaging (DWI) in the evaluation of deep infiltrating endometriosis (DIE). MATERIALS AND METHODS: In a prospective single-center study, DWI was added to the standard MRI protocol in 56 consecutive patients with known or suspected endometriosis. Endometriotic lesions as well as (functional) ovarian cysts were analyzed for location, size, and signal intensity on T1, T2, and DWI. Apparent diffusion coefficient (ADC) values were calculated using b-values of 50, 400, 800, and 1200 s/mm(2). Statistical analysis included the Spearman correlation coefficient, Mann-Whitney U, and Kruskal-Wallis tests. RESULTS: A total of 112 lesions (62 endometrial cysts and 48 DIE) were detected, 60 of which were large enough to analyze. Mean ADC values of endometrial cysts and functional ovarian cysts were 1.11 x 10(-3)/mm(2)/s and 2.14 x 10(-3)/mm(2)/s, respectively. Mean ADC values of DIE retrocervical, infiltrating the colon, and bladder were 0.70 x 10(-3)/mm(2)/s, 0.79 x 10(-3)/mm(2)/s, and 0.76 x 10(-3)/mm(2)/s, respectively. ADC values of DIE did not show a significant difference between varying pelvic locations (P = 0.63). CONCLUSION: Results of our study suggest that ADC values of DIE are consistently low, without significant difference between pelvic locations.

Predictors of abnormal chest CT after blunt trauma: a critical appraisal of the literature.

AIM: To identify and to evaluate predictors that determine whether chest computed tomography (CT) is likely to reveal relevant injuries in adult blunt trauma patients. METHODS: After a comprehensive literature search for original studies on blunt chest injury diagnosis, two independent observers included studies on the accuracy of parameters derived from history, physical examination, or diagnostic imaging that might predict injuries at (multidetector row) CT in adults and that allowed construction of 2x2 contingency tables. For each article, methodological quality was scored and relevant predictors for injuries at CT were extracted. For each predictor, sensitivity, specificity, positive and negative likelihood ratio and diagnostic odds ratio (DOR) including 95% confidence intervals were calculated. RESULTS: Of 147 articles initially identified, the observers included 10 original studies in consensus. Abnormalities at physical examination (abnormal respiratory effort, need for assisted ventilation, reduced airentry, coma, chest wall tenderness) and pelvic fractures were significant predictors (DOR: 2.1-6.7). The presence of any injuries at conventional radiography of the chest (eight articles) was a more powerful significant predictor (DOR: 2.2-37). Abnormal chest ultrasonography (four articles) was the most accurate predictor for chest injury at CT (DOR: 491-infinite). CONCLUSION: The current literature indicates that in blunt trauma patients with abnormal physical examination, abnormal conventional radiography, or abnormal ultrasonography of the chest, CT was likely to reveal relevant chest injuries. However, there was no strong evidence to suggest that CT could be omitted in patients without these criteria, or whether these findings are beneficial for patients.

Incremental diagnostic value of epicardial adipose tissue for the detection of functionally relevant coronary artery disease.

BACKGROUND AND AIM: To determine the incremental diagnostic value of epicardial adipose tissue (EAT) volume in addition to the coronary artery calcium (CAC) score for detecting hemodynamic significant coronary artery disease (CAD). METHODS AND RESULTS: 122 patients (mean age 61 ± 10 years, 61% male) without a previous cardiac history underwent a non-contrast CT scan for calcium scoring and EAT volume measurements. Subsequently all patients underwent invasive coronary angiography (ICA) in conjunction with fractional flow reserve (FFR) measurements. A stenosis >90% and/or a FFR ≤0.80 were considered significant. Mean EAT volume and CACscore were 128 ± 51 cm(3) and 418 ± 704, respectively. The correlation between EAT volume and the CACscore was poor (r = 0.11, p = 0.24). Male gender (odds ratio [OR] 2.86, p = 0.01), CACscore ([cut-off value 100] OR 3.31, p = 0.003, and EAT volume ([cut-off value 92 cm(3)] OR 4.28, p = 0.01) were associated with flow-limiting disease. The multivariate model revealed that only male gender (OR 2.50, p = 0.045), CAC score (OR 3.60, p = 0.005), and EAT volume (OR 4.95, p = 0.02) were independent predictors of myocardial ischemia. Using the cut-off values of 100 (CAC score) and 92 cm(3) (EAT volume), sensitivity, specificity, negative predictive value, positive predictive value, and accuracy for detecting functionally relevant CAD as indicated by FFR were 71, 57, 77, 50 and 63% and 91, 29, 85, 44 and 52% for the CACscore and EAT volume, respectively. Adding EAT volume to the CAC score and cardiovascular risk factors did not enhance diagnostic performance for the detection of significant CAD (p = 0.57). CONCLUSION: EAT volume measurements have no diagnostic value beyond calcium scoring and cardiovascular risk factors in the detection of hemodynamic significant CAD.

Vertebral fracture assessment using a semiquantitative technique.

The assessment of vertebral fracture by conventional radiography has been refined and improved using either semiquantitative or quantitative criteria. The inter- and intraobserver variability was determined for a semiquantitative visual approach that we routinely use in clinical studies for assessing prevalent and incident vertebral fractures. In addition, the semiquantitative approach was compared with a quantitative morphometric approach. The incidence and prevalence of vertebral fractures were determined in 57 postmenopausal women (age 65-75 years) by three independent observers. The radiographic basis for fracture definitions and the source of interobserver agreement for the semiquantitative technique. We conclude that the semiquantitative approach can be applied reliably in vertebral fracture assessment when performed using well-defined criteria.

Course of bone mass during and after hormonal replacement therapy with and without addition of nandrolone decanoate.

A total of 33 women with postmenopausal osteoporosis were matched pairwise by age, years since menopause, and body mass index and randomized to receive either cyclic estrogen-progestagen replacement treatment (group 1) or the same treatment plus nandrolone decanoate (ND; group 2). Both groups were treated during 3 years and subsequently followed for another year off treatment. A year after cessation of the treatment the distal forearm bone mineral content in group 2 was significantly higher than that in group 1. Bone mass measurements in the axial skeleton already showed a significant difference in favor of group 2 after 3 years treatment, which persisted during the year off treatment. The decline in lumbar bone mineral mass and density in the 1 year off treatment was similar in both groups. Correction for body mass did not change these results. Bone turnover parameters did not show significant differences between the two groups after cessation of treatment. A higher muscle mass, induced by ND, could partly explain the differences between the groups since even 1 year after treatment was stopped an increased serum creatinine level was still observed in group 2.

Universal standardization for dual x-ray absorptiometry: patient and phantom cross-calibration results.

The comparison of patient data among different dual x-ray absorptiometry (DXA) scanners is complicated because no universally accepted cross-calibration procedure or standard currently exists. This study was performed under the auspices of the International DXA Standardization Committee to establish appropriate cross-calibration parameters. Posteroanterior (PA) lumbar spine measurements of 100 women, ages 20-80 years (mean 52.6 +/- 16, range of BMD = 0.4-1.6 g/cm2) were obtained on a Norland XR26 Mark II, a Lunar DPX-L, and a Hologic QDR 2000 densitometer using standard procedures (pencil beam mode for all three scanners). Area, BMC, and BMD results from the different scanners were compared for all patients. In addition, the European spine phantom (ESP) and the European spine phantom prototype (ESP prototype), as well as standard phantoms from all three manufacturers, were evaluated on the three systems. To achieve universal scanner calibration, we used the intercept and slope of the patient's correlations and the value of the middle vertebra of the ESP as a reference point in a series of standardization formulas, and we have expressed the results as sBMD (mg/cm2). The correlations of the patients' spinal BMD values were excellent for each of the three scanner pairs. The average absolute difference in patient spinal BMD values (L2-4) between Hologic and Norland was 0.012 g/cm2 (1.3%); it was 0.113 g/cm2 (11.7%) between Hologic and Lunar and 0.118 g/cm2 (12.2%) between Norland and Lunar. The phantoms' regression lines approximated those of the patient regression lines, and the phantoms with only one measurement point were very close to the patients' regression lines. After applying the standardization formulas, the average absolute differences for the 100 patients were 28 mg/cm2 (2.7%) for Hologic/Norland, 23 mg/cm2 (2.2%) for Hologic/Lunar, and 29 mg/cm2 (2.8%) for Norland/Lunar. Average BMD results for the patients before correction were 0.972 mg/cm2 for Hologic, 1.100 g/cm2 for Lunar, and 0.969 g/cm2 for Norland. After correction, sBMD results for patients were 1045 mg/cm2 for Hologic, 1047 mg/cm2 for Lunar, and 1043 mg/cm2 for Norland. The standardization approach as performed in our study provided compatibility of DXA results obtained on different scanners.

Measurement of bone mineral density at the spine and proximal femur by volumetric quantitative computed tomography and dual-energy X-ray absorptiometry in elderly women with and without vertebral fractures.

The goal of this study was to determine the effect of vertebral fracture status on trabecular bone mineral density (BMD) measurements obtained in the proximal femur and spine by helical volumetric quantitative computed tomography (vQCT). The study population consisted of 71 Italian women (average age 73 +/- 6) years. This group included 26 subjects with radiographically confirmed atraumatic vertebral fractures and 45 controls. The subjects received helical CT scans of the L1 and L2 vertebral bodies and the hip. The three-dimensional CT images were processed using specialized image analysis algorithms to extract measurements of trabecular, cortical, and integral BMD in the spine and hip. To compare the vQCT results with the most widely used clinical BMD measurement, dual X-ray absorptiometry (DXA) scans of the anteroposterior (AP) spine and proximal femur were also obtained. The difference between the subjects with vertebral fractures and the age-matched controls was computed for each BMD measure. All BMD measurements showed statistically significant differences, which ranged from 7% to 22% between subjects with fractures and controls. Although, given our small sample size, we could not detect statistically significant differences in discriminatory power between BMD techniques, integral BMD of the spine measured by vQCT and DXA tended to show stronger associations with fracture status (0.001 < p < 0.004). Measurements by QCT and DXA at the hip were also associated with vertebral fracture status, although the association of DXA BMD with fracture status was explained largely by differences in body weight between subjects with vertebral fractures and controls.

Radiographic absorptiometry of the phalanges in healthy children and in girls with Turner syndrome.

Although bone mineral status in children has been measured with various techniques, information about development of the actual bone mass density during childhood and adolescent growth is scarce. Our modified radiographic absorptiometry (RA) determines bone mass density (BMaD) three dimensionally at the diaphyseal and metaphyseal site of the middle phalanx of the left second digit, representing predominantly cortical (50% site) and trabecular bone compartments (25% site), respectively. The objectives of this study were to establish reference curves with 95% prediction intervals of BMaD in relation to bone age (BA) during childhood and adolescence (N = 303) determined by RA. The specific effects of female puberty on BMaD were studied comparing the values of 110 untreated girls with Turner syndrome (TS) with those of the female reference group. For either sex, a piecewise linear model with one inflection point (IP) was postulated for the relationship of both the 25% and 50% site with BA. The IPs appeared at exactly the same BA (11.5 "years") for both the 25% and 50% site in boys and for the 25% site in girls. However, in girls the 50% site IP appeared 0.25 "years" later. All BMaD values to the left of the IPs showed little increase with age. In contrast, the slopes to the right of the IPs showed in both genders regression coefficients of approximately 0.05 for the 25% site. For the 50% site, the regression coefficient in girls was markedly higher (0.075) than in boys (0.058), resulting only in girls in a significant difference between the 25% and the 50% site to the right of the IP (p = 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)

Distribution of trabecular and cortical bone related to geometry. A quantitative computed tomography study of the femoral neck.

METHODS: The relation between geometry and the distribution of trabecular and cortical bone mass and density in the human femoral neck was evaluated with quantitative computed tomography (QCT). Quantitative computed tomography data were obtained from 2-mm thick computed tomography slices of 20 human femur necks in vitro. A standardized scan position in each femur was used with the smallest cross-section as reference point. RESULTS: When trabecular bone mass (TrBM) and cortical bone mass were presented as percentage of total bone mass (ToBM), it was found that, starting at the cranial (head) side, ToBM consists of 78% TrBM. About 21% of ToBM can be found as TrBM at the caudal (trochanter) side. At the smallest cross-sectional volume TrBM is 33% of ToBM. For every 2-mm slice, an average decrease of 5% TrBM can be seen. CONCLUSIONS: These data show that geometry and bone mass distribution are related. Whereas total bone mass remains relatively stable, the cortical and trabecular bone mass changes extensively. This implies that QCT measurements in the femoral neck depend highly on midneck positioning.

Evaluation of postprocessing dual-energy methods in quantitative computed tomography. Part 1. Theoretical considerations.

Five postprocessing methods for dual-energy quantitative computed tomography of the vertebral body were evaluated theoretically. The methods were compared by transforming the original sets of equations to a standard set. Only two of these methods produced optimal results, namely the basic approach of Goodsitt et al and the method of Nickoloff et al. The calibration approach of Goodsitt et al will produce optimal results only if calibration materials are available that mimic the anatomic constituents of the vertebral body better than those available currently. Theoretically, the methods of Cann et al and of Laval-Jeantet et al will not produce optimal results.

Evaluation of postprocessing dual-energy methods in quantitative computed tomography. Part 2. Practical aspects.

Three facets of dual-energy quantitative computed tomography are studied: (1) the algorithm for postprocessing data (the methods of Cann, Laval-Jeantet et al, Goodsitt et al [two methods], and Nickoloff et al); (2) the influence of choice of tissue-equivalent materials for calibration; and (3) the difference between central and peripheral calibration. The different tissue-equivalent materials include bone mineral-equivalent (K2HPO4 solutions and calcium hydroxyapatite), fat-equivalent (liquid paraffin, polyethylene, and 70% ethanol solution), and red marrow-equivalent (plastic). Deviation from the manufacturer's quoted content is least with central positioning of the calibration materials. The accuracy of estimates is best when the same tissue-equivalent materials are used for calibration that are being measured. The deviations produced by the use of different tissue-equivalent materials indicate the importance of using materials that mimic the components of bone most closely. The two methods of Goodsitt et al and the method of Nickoloff et al produced the best results.

Tibial quantitative ultrasound versus whole-body and lumbar spine DXA in a Dutch pediatric and adolescent population.

RATIONALE AND OBJECTIVES: To understand normal bone development, studies in healthy children and adolescents are important. To assess the applicability of tibial quantitative ultrasound measurements (QUS) in children, we performed a study that compared dual-energy x-ray absorptiometry (DXA) of the lumbar spine and whole body with tibial QUS. METHODS: For this study we recruited 146 Dutch children and adolescents, 58 boys (median age, 14.1 years; range, 7.6-23.4 years) and 88 girls (median age, 18.0 years; range, 7.6-23.5 years). Tanner stage, weight, and height were assessed for all participants. Bone mineral density (BMD; g x cm(-2)) of the whole body and lumbar spine (L2-L4) and bone mineral apparent density (BMAD) of the lumbar spine (g x cm(-3)) were assessed by using the Lunar DPXL. For tibial QUS, the Soundscan compact system was used. RESULTS: Both lumbar as well as whole-body BMD showed a strong, significant correlation with tibial QUS in boys and girls: rtotal body boys = 0.81, rtotal body girls = 0.77, rlumbar spine boys = 0.79, and rlumbar spine girls = 0.72. Lumbar spine BMAD also showed significant correlations with tibial QUS: rboys= 0.63 and rgirls = 0.63 (for all correlations, P < 0.001). CONCLUSIONS: Our study showing strong, significant correlations between DXA and tibial QUS measurements suggests that tibial QUS is a technique that may be applicable in children and adolescents.

Selection of fat-equivalent materials in postprocessing dual-energy quantitative CT.

Postprocessing dual-energy QCT is supposed to be able to predict the bone mineral more accurately than single-energy QCT. In addition, the fat content in the vertebral body can be determined. To this aim, some methods include fat-equivalent materials in the calibration device. However, the choice of an appropriate fat-equivalent material is difficult. To solve this selection problem, a method has been developed in which the x-ray interactions of tissue are characterized by three energy-independent parameters. For five different known constituents of anatomical fat, fat-equivalent materials are evaluated. It is shown that it is not possible to find one fat-equivalent material for all anatomical fat compositions. For this reason, the influence of a mismatch between the characterization parameters of anatomical fat compositions and fat-equivalent materials has been evaluated. It is shown that a mismatch in tissue characterization parameters can result in deviations of 10% in the bone mineral content and more than 300% in the estimated fat contents.

Absent correlation between vaginal bleeding and oestradiol levels or endometrial morphology during tibolone use in early postmenopausal women.

OBJECTIVE: To investigate a potential correlation between vaginal bleeding and oestradiol (E2) levels/endometrial morphology in early postmenopausal women using tibolone (Livial(R)). METHODS: A 2-year randomised placebo-controlled study of 94 healthy women, 1-3 years after spontaneous menopause, receiving either placebo (n=23), 1.25 mg/day (n=36) or 2.5 mg/day (n=35) tibolone. Episodes of vaginal bleeding throughout the 2-year study period were recorded. Age, age of menopause, months since menopause and body mass index were recorded. Serum E2 levels were assessed at baseline and at 3-month intervals throughout the study period. In case of vaginal bleeding, endometrium morphology was assessed by Vabra Curettage. RESULTS: Fifty-one percent (n=18, P<0.05) of women in the 2.5 mg/day tibolone group and 44% (n=16, P=0.07) in the 1.25 mg/day tibolone group presented with at least one period of vaginal bleeding, compared with 22% (n=5) in the placebo group. The women who bled in the placebo group were younger (P<0.01), had menopause at an earlier age (P<0.05), had a shorter duration since menopause (P<0.05) and had a higher median E2 serum level prior to bleeding (P<0.05). In contrast, in both tibolone groups, no determinants could be found for the vaginal bleeding. Ninety percent of the first bleedings occurred within 9 months after starting the treatment. At Vabra endometrium sampling, there was no evidence of endometrial stimulation. CONCLUSIONS: In the present study, early postmenopausal women using 1.25 or 2.5 mg/day tibolone are 2-2.5 times more likely to present with vaginal bleeding compared with placebo (P<0.05) without evidence of higher serum E2 levels or endometrial stimulation.

Increased loss of trabecular but not cortical bone density, 1 year after discontinuation of 2 years hormone replacement therapy with Tibolone.

OBJECTIVE: Assessment of loss of bone density (BD) 1 year after a 2-year period of hormone replacement therapy (HRT) with two doses of Tibolone as compared to placebo in early post-menopausal women. METHODS: Sixty-four out of 84 women (1-3 years following spontaneous menopause) who completed a 2-year randomised, placebo controlled study to evaluate effects of Tibolone participated in this follow-up study. Quantitative computed tomography was used to exclusively measure trabecular BD, microdensitometry of the mid-phalangeal shaft was used for estimation of cortical BD and biochemical markers of bone metabolism were assessed, 1 year after discontinuation of Tibolone. The study group received either placebo (n = 16), 1.25 mg/day Tibolone (n = 25) or 2.5 mg/day Tibolone (n = 23). RESULTS: Observations revealed a significantly greater decrease in trabecular BD during the post-trial year in both treatment groups compared to the placebo group (for 1.25 mg/day Tibolone, -6.0%, 95% CI -8.4 to -3.5; for 2.5 mg/day Tibolone, -10.0%, 95% CI: -12.9 to -6.9). In contrast, there was no significant difference in loss of phalangeal BD in both treatment groups compared to placebo. Biochemical markers (serum alkaline phosphatase, urinary excretion of hydroxyproline and calcium) do not suggest an increased bone turnover comparing Tibolone groups to placebo, 1 year after cessation of Tibolone. CONCLUSION: The present study suggests an increased loss of trabecular but not cortical BD as compared to the placebo group in the first year after cessation of HRT with Tibolone in early post-menopausal women.