Pamidronate results in symptom control of hypertrophic pulmonary osteoarthropathy in cystic fibrosis

Hypertrophic pulmonary osteoarthropathy (HPOA) may complicate the advanced lung disease that is associated with cystic fibrosis, resulting in severe joint pain and early-morning stiffness. Symptoms are usually controlled with the administration of nonsteroidal anti-inflammatory drugs, physiotherapy, and, on occasions, oral corticosteroids. I This report describes a case of refractory HPOA with complete remission following the administration of IV pamidronate, which is a potent inhibitor of osteoclastic bone resorption. Symptom relief resulted for up to 3 months, but repeated courses of pamidronate have been required to maintain symptom control.

Influence of left ventricular size and hemodynamics on the systolic longitudinal myocardial Doppler velocity response to stress

Background Systolic myocardial Doppler velocity accurately identifies coronary artery disease. However, these velocities may be affected by age, hemodynamic responses to stress, and left ventricular cavity size. We sought to examine the influences of these variables on myocardial velocity during dobutamine stress in patients with normal wall motion. Methods One hundred seventy-nine consecutive patients with normal dobutamine echocardiograms were studied. Color myocardial tissue Doppler data were obtained at rest and peak stress, and peak systolic myocardial velocity (PSV) was measured in all basal and midventricular segments. Velocities at rest and peak stress were compared with left ventricular diastolic and systolic volumes, blood pressure, heart rate, and age by Pearson correlation and interdecile analysis by use of analysis of variance. Results The only clinical variable correlating with velocity was age; PSV showed only mild correlation with age at rest (r(2) = 0.01, P = .001) and peak stress (r(2) = 0.02, P = .001), but the normal peak velocity was significantly different between the extremes of age (<44 years and >74 years). There was very weak correlation of PSV with systolic and diastolic blood pressure (r(2) < 0.01), heart rate (r(2) < 0.01), systemic vascular resistance (r(2) = 0.08), and left ventricular volumes (r(2) < 0.01). Conclusions Peak systolic velocity during dobutamine stress is relatively independent of hemodynamic factors and left ventricular cavity size. The extremes of age may influence peak systolic Doppler velocities. These results suggest that peak systolic velocity may be a robust quantitative measure during dobutamine echocardiography across most patient subgroups.

Myocardial abnormalities in hypertensive patients with normal and abnormal left ventricular filling: a study of ultrasound tissue characterization and strain

Abnormal left ventricular (LV) filling is common, but not universal, in hypertensive LV hypertrophy (LVH). We sought to elucidate the relative contributions of myocardial structural changes, loading and hypertrophy to LV dysfunction in 113 patients: 85 with hypertensive LVH and 28 controls without LVH and with normal filling. Patients with normal dobutamine stress echocardiography and no history of coronary artery disease were selected, in order to exclude a contribution from ischaemia or scar. Abnormal LV filling was identified in 65 LVH patients, based on Doppler measurement of transmitral filling and annular velocities. All patients underwent grey-scale and colour tissue Doppler imaging from three apical views, which were stored and analysed off line. Integrated backscatter (113) and strain rate imaging were used to detect changes in structure and function; average cyclic variation of 113, strain rate and peak systolic strain were calculated by averaging each segment. Calibrated 113 intensity, corrected for pericardial 113 intensity, was measured in the septum and posterior wall from the parasternal long-axis view. Patients with LVH differed significantly from controls with respect to all backscatter and strain parameters, irrespective of the presence or absence of abnormal LV filling. LVH patients with and without abnormal LV filling differed with regard to age, LV mass and incidence of diabetes mellitus, but also showed significant differences in cyclic variation (P < 0.01), calibrated 113 in the posterior wall (P < 0.05) and strain rate (P < 0.01), although blood pressure, heart rate and LV systolic function were similar. Multivariate logistic regression analysis demonstrated that age, LV mass index and calibrated IB in the posterior wall were independent determinants of abnormal LV filling in patients with LVH. Thus structural and functional abnormalities can be detected in hypertensive patients with LVH with and without abnormal LV filling. In addition to age and LVH, structural (not functional) abnormalities are likely to contribute to abnormal LV filling, and may be an early sign of LV damage. 113 is useful for the detection of myocardial abnormalities in patients with hypertensive LVH.

Dimensionality and clinical importance of pain and disability in hand osteoarthritis: Development of the Australian/Canadian (AUSCAN) Osteoarthritis Hand Index

Objective: To develop a reliable, valid, and responsive self-administered questionnaire to probe pain, stiffness and physical disability in patients with osteoarthritis (OA) of the hand. Design: In order to assess the dimensionality of the symptomatology of hand OA, a self-administered questionnaire was developed to probe various aspects of pain (10 items), stiffness (two items), and physical function (83 items). The question inventory was generated from eight existing health status measures and an interactive process involving four rheumatologists, two physiotherapists, and an orthopaedic surgeon. Results: Face-to-face interviews were conducted with 50 OA hand patients; 39 females and 11 males with mean age 62.8 years and mean disease duration 9.4 years. Items retained were those which fulfilled specified selection criteria: prevalence greater than or equal to60% and mean importance score approximating or exceeding 2.0 Item exclusion criteria included low prevalence, gender-based, ambiguous, duplicates or similarities, alternatives, composite items, and items that were too restrictive. This process resulted in five pain, one stiffness and nine function items which have been proposed for incorporation in the AUSCAN Index. Conclusions: Using a traditional development strategy, we have constructed a self-administered multi-dimensional outcome measure for assessing hand OA. The next stage includes reliability, validity and responsiveness testing of the 15-item questionnaire. (C) 2002 OsteoArthritis Research Society Intenational. Published by Elsevier Science Ltd. All rights reserved.

A prospective, randomized, pragmatic, health outcomes trial evaluating the incorporation of hylan G-F 20 into the treatment paradigm for patients with knee osteoarthritis (Part 1 of 2): clinical results

Objective: First, to assess the clinical effectiveness of hylan G-F 20 in an appropriate care treatment regimen (as defined by the American College of Rheumatology (ACR) 1995 guidelines) as measured by validated disease-specific outcomes and health-related quality of life endpoints for patients with osteoarthritis (OA) of the knee. Second, to utilize the measures of effectiveness and costs in an economic evaluation (see accompanying manuscript). Design: A total of 255 patients with OA of the knee were enrolled by rheumatologists or orthopedic surgeons into a prospective, randomized, open-label, 1-year, multi-centred trial, conducted in Canada. Patients were randomized to 'Appropriate care with hylan G-F 20' (AC+H) or 'Appropriate care without hylan G-F 20' (AC). Data were collected at clinic visits (baseline, 12 months) and by telephone (1, 2, 4, 6, 8, 10, and 12 months). Results: The AC+H group was superior to the AC group for all primary (% reduction in mean Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain scale: 38% vs 13%, P=0.0001) and secondary effectiveness outcome measures. These differences were all statistically significant and exceeded the 20% difference between groups seta priori by the investigators as the minimum clinically important difference. Health-related quality of life improvements in the AC+H group were statistically superior for the WOMAC pain, stiffness and physical function (all P

Clinical evaluation of the WOMAC 3.0 OA Index in numeric rating scale format using a computerized touch screen version

Background: The Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index is a previously described self-administered questionnaire covering three domains: pain, stiffness and function. It has been validated in patients with osteoarthritis (OA) of the hip or knee in a paper-based format. Aim: To validate the WOMAC 3.0 using a numerical rating scale in a computerized touch screen format allowing immediate evaluation of the questionnaire. In the computed version cartoons, written and audio instruments were included in order facilitate application. Methods: Fifty patients, demographically balanced, with radiographically proven primary hip or knee OA completed the classical paper and the new computerized WOMAC version. Subjects were randomized either to paper format or computerized format first to balance possible order effects, Results: The intra-class correlation coefficients for pain, stiffness and function values were 0.915, 0.745 and 0.940, respectively. The Spearman correlation coefficients for pain, stiffness and function were 0.88, 0.77 and 0.87, respectively. Conclusion: These data indicate that the computerized WOMAC OA index 3.0 is comparable to the paper WOMAC in all three dimensions. The computerized version would allow physicians to get an immediate result and if present a direct comparison with a previous exam. (C) 2002 OsteoArthritis Research Society International. Published by Elsevier Science Ltd. All rights reserved.

A comparative study of telephone versus onsite completion of the WOMAC 3.0 Osteoarthritis Index

Objective. Outcome assessment in clinical trials using the Western Ontario and McMaster University (WOMAC 3.0) Osteoarthritis Index is traditionally achieved through self-administration of the Index. However, in other areas of clinical measurement, telephone administration has been shown to be a reliable method of acquiring data that are both accurate and complete. To address this issue in knee osteoarthritis (OA), we conducted a comparative study of telephone administration by interviewer of WOMAC LK3.0 versus onsite self-completion at the hospital. Methods. Fifty consenting patients with knee OA were randomized to complete the WOMAC LK3.0 Index by telephone interview one day, followed by onsite completion the following day, or vice versa. Neither patients nor interviewers had access to any prior scores. Results. The mean age of the 50 patients was 66.3 years (range 44-82); 34 (68%) were female and 16 (32%) male. There was excellent agreement between the mean office and telephone scores, with mean differences for the WOMAC LK3.0 pain, stiffness, and function subscale scores and total score of 0.09, 0.12, 0.78, and 0.98, respectively. These differences were well within the respective protocol defined equivalence criteria of +/- 1.7, +/- 0.9, +/- 6.4, and +/- 9.1, and represented differences from office scores of 0.9, 2.6, 2.4, and 2.2%, respectively. Conclusion. The use of telephone interviews for the WOMAC LK3.0 Index is a valid method of obtaining OA outcome measurements. These observations have important implications for designing data acquisition strategies for future OA clinical trials and for longterm observational studies.

How reliably do rheumatologists measure shoulder movement?

Objective: To assess the intrarater and interrater reliability among rheumatologists of a standardised protocol for measurement of shoulder movements using a gravity inclinometer. Methods: After instruction, six rheurnatologists independently assessed eight movements of the shoulder, including total and glenohumeral flexion, total and glenohumeral abduction, external rotation in neutral and in abduction, internal rotation in abduction and hand behind back, in random order in six patients with shoulder pain and stiffness according to a 6x6 Latin square design using a standardised protocol. These assessments were then repeated. Analysis of variance was used to partition total variability into components of variance in order to calculate intraclass correlation coefficients (ICCs). Results: The intrarater and interrater reliability of different shoulder movements varied widely. The movement of hand behind back and total shoulder flexion yielded the highest ICC scores for both intrarater reliability (0.91 and 0.83, respectively) and interrater reliability (0.80 and 0.72, respectively). Low ICC scores were found for the movements of glenohumeral abduction, external rotation in abduction, and internal rotation in abduction (intrarater ICCs 0.35, 0.43, and 0.32, respectively), and external rotation in neutral, external rotation in abduction, and internal rotation in abduction (interrater ICCs 0.29, 0.11, and 0.06, respectively). Conclusions: The measurement of shoulder movements using a standardised protocol by rheumatologists produced variable intrarater and interrater reliability. Reasonable reliability was obtained only for the movement of hand behind back and total shoulder flexion.

Coexistence of stability and mobility in postural control: evidence from postural compensation for respiration

This study evaluated the extent to which movement of the lower limbs and pelvis may compensate for the disturbance to posture that results from respiratory movement of the thorax and abdomen. Motion of the neck, pelvis, leg and centre of pressure (COP) were recorded with high resolution in conjunction with electromyographic activity (EMG) of flexor and extensor muscles of the trunk and hip. Respiration was measured from ribcage motion. Subjects breathed quietly, and with increased volume due to hypercapnoca (as a result of breathing with increased dead-space) and a voluntary increase in respiration. Additional recordings were made during apnoea. The relationship between respiration and other parameters was measured from the correlation between data in the frequency domain (i.e. coherence) and from time-locked averages triggered from respiration. In quiet standing, small angular displacements (similar to0.5degrees) of the trunk and leg were identified in raw data. Correspondingly, there were peaks in the power spectra of the angular movements and EMG. While body movement and EMG were coherent with respiration (>0.5), the coherence between respiration and COP displacement was low (

Age does not influence the bone response to treadmill exercise in female rats

Purpose: Because it is believed that bone may respond to exercise differently at different ages, we compared bone responses in immature and mature rats after 12 wk of treadmill running. Methods: Twenty-two immature (5-wk-old) and 21 mature (17-wk-old) female Sprague Dawley rats were randomized into a running (trained, N = 10 immature, 9 mature) or a control group (controls, N 12 immature, 12 mature) before sacrifice 12 wk later. Rats ran on a treadmill five times per week for 60-70 min at speeds up to 26 m.min(-1). Both at baseline and after intervention, we measured total body, lumbar spine, and proximal femoral bone mineral, as well as total body soft tissue composition using dual-energy x-ray absorptiometry (DXA) in vivo. After sacrificing the animals, we measured dynamic and static histomorphometry and three-point bending strength of the tibia. Results: Running training was associated with greater differences in tibial subperiosteal area, cortical cross-sectional area, peak load, stiffness, and moment of inertia in immature and mature rats (P < 0.05). The trained rats had greater periosteal bone formation rates (P < 0.01) than controls, but there was no difference in tibial trabecular bone histomorphometry. Similar running-related gains were seen in DXA lumbar spine area (P = 0.04) and bone mineral content (BMC; P = 0.03) at both ages. For total body bone area and BMC, the immature trained group increased significantly compared with controls (P < 0.05), whereas the mature trained group gained less than did controls (P < 0.01). Conclusion: In this in vivo model, where a similar physical training program was performed by immature and mature female rats, we demonstrated that both age groups were sensitive to loading and that bone strength gains appeared to result more from changes in bone geometry than from improved material properties.

Effect of manual hyperinflation on hemodynamics, gas exchange, and respiratory mechanics in ventilated patients

The authors investigated the effect of manual hyperinflation (MHI) with set parameters applied to patients on mechanical ventilation on hemodynamics, respiratory mechanics, and gas exchange. Sixteen critically ill patients post-septic shock, with acute lung injury, were studied. Heart rate, arterial pressure, and mean pulmonary artery pressure were recorded every minute. pulmonary artery occlusion pressure, cardiac output, arterial blood gases, and dynamic compliance (C-dyn) were recorded pre- and post-MHI. From this, systemic vascular resistance index (SVRI), cardiac index, oxygen delivery, and partial pressure of oxygen:fraction of inspired oxygen (PaO2:FiO(2)) ratio were calculated. There were significant increases in SVRI (P < 0.05) post-MHI and diastolic arterial pressure (P < 0.01)during MHI. C-dyn increased post-MHI (P < 0.01) and was sustained at 20 minutes post-MHI (P < 0.01). Subjects with an intrapulmonary cause of lung disease had a significant decrease (P = 0.02) in PaO2:FiO(2), and those with extrapulmonary causes of lung disease had a significant increase (P < 0.001) in PaO2:FiO(2) post-MHI. In critically ill patients, MHI resulted in an improvement in lung mechanics and an improvement in gas exchange in patients with lung disease due to extrapulmonary events and did not result in impairment of the cardiovascular system.

Effects of the vasopeptidase inhibitor, omapatrilat, in 723 patients with coronary heart disease

Introduction Among individuals with a history of myocardial infarction (MI), higher levels of blood pressure (BP) are associated with increased long-term risks of death from coronary heart disease. Treatment with a BP-lowering regimen, based on omapatrilat may result in greater clinical benefits than treatment with a regimen based on a regular angiotensin-converting enzyme (ACE) inhibitor because of more favourable effects on the renin-angiotensin-aldosterone system. Methods Seven hundred and twenty-three clinically stable patients with a history of MI or unstable angina, and a mean entry BP of 134/77 mmHg, were randomised to six months treatment with omapatrilat 40 mg, omapatrilat 20 mg, or matching placebo. Results After six months, mean BP levels (systolic/diastolic) in the omapatrilat 40 mg group were reduced by 4.3/ 2.9 mmHg (95% confidence interval 1.3 to 7.2/1.2 to 4.6). Mean BP levels in the omapatrilat 20 mg group were reduced by 4.6/1.0 mmHg (1.6 to 7.6/-0.7 to 2.6) in comparison with the placebo group. Both doses of omapatrilat also produced significant decreases in plasma ACE activity and significant increases in levels of plasma renin activity, atrial natriuretic peptide, endothelin and homocysteine (p

Association of hypertension and hypokalemia with Cushing's syndrome caused by ectopic ACTH secretion: a series of 58 cases.

Cushing's syndrome is associated with hypertension in approximately 80% of cases. Hypertension contributes to the marked increased mortality risk of past or current Cushing's syndrome, largely because of increased cardiovascular risk. Observation of the pathophysiological effect of chronically elevated ACTH and cortisol values in patients with ectopic ACTH secretion complements the available data from acute studies of the effects of ACTH and glucocorticoid infusions in normal volunteers. In a retrospective case review, we identified 58 patients with Cushing's syndrome caused by ectopic ACTH secretion, who were treated at the National Institutes of Health between 1983-1997. The diagnosis of an ectopic ACTH cause was confirmed by inferior petrosal sinus sampling and/or pathologic examination of tumor. The commonest causes were bronchial carcinoid (40%) and thymic carcinoid (10%), but 18 of 58 (31%) patients had an unknown source of ectopic ACTH. Hypertension (systolic blood pressure >140 mmHg and/or diastolic blood pressure >90 mmHg in adults) was noted in 45 of 58 (78%) ectopic Cushing's patients, a prevalence similar to that noted in other endogenous Cushing's syndrome etiologies. Hypertension was severe, deemed to require 3 or more drugs by the treating physicians, in 26 of 58 (45%) patients. Hypokalemia was much more prevalent than in patients with other causes of Cushing's syndrome, affecting 33 of 58 (57%) patients. The range of plasma ACTH (17-1557 pg/mL, normal

Discrete element modelling of power draw of tumbling mills

The power required to operate large mills is typically 5-10 MW. Hence, optimisation of power consumption will have a significant impact on overall economic performance and environmental impact. Power draw modelling results using the discrete element code PFC3D have been compared with results derived from the widely used empirical Model of Morrell. This is achieved by calculating the power draw for a range of operating conditions for constant mill size and fill factor using two modelling approaches. fThe discrete element modelling results show that, apart from density, selection of the appropriate material damping ratio is critical for the accuracy of modelling of the mill power draw. The relative insensitivity of the power draw to the material stiffness allows selection of moderate stiffness values, which result in acceptable computation time. The results obtained confirm that modelling of the power draw for a vertical slice of the mill, of thickness 20% of the mill length, is a reliable substitute for modelling the full mill. The power draw predictions from PFC3D show good agreement with those obtained using the empirical model. Due to its inherent flexibility, power draw modelling using PFC3D appears to be a viable and attractive alternative to empirical models where necessary code and computer power are available.

The genetics of coronary heart disease: the contribution of twin studies

Despite the decline in coronary heart disease in many European countries, the disease remains an enormous public health problem. Although we know a great deal about environmental risk factors for coronary heart disease, a heritable component was recognized a long time ago. The earliest and best known examples of how our genetic constitution may determine cardiovascular risk relate to lipoprotein(a), familial hypercholesterolaemia and apolipoprotein E. In the past 20 years a fair number of polymorphisms assessed singly have shown strong associations with the disease but most are subject to poor repeatability. Twins constitute a compelling natural experiment to establish the genetic contribution to coronary heart disease and its risk factors. GenomEUtwin, a recently funded Framework 5 Programme of the European Community, affords the opportunity of comparing the heritability of risk factors in different European Twin Registries. As an illustration we present the heritabilities of systolic and diastolic blood pressure, based on data from over 4000 twin pairs from six different European countries and Australia. Heritabilities for systolic blood pressure are between 52 and 66% and for diastolic blood pressure between 44 and 66%. There is no evidence of sex differences in heritability estimates and very little to no evidence for a significant contribution of shared family environment. A non-twin based prospective case/cohort study of coronary heart disease and stroke (MORGAM) will allow hypotheses relating to cardiovascular disease, generated in the twin cohorts, to be tested prospectively in adult populations. Twin studies have also contributed to our understanding of the life course hypothesis, and GenomEUtwin has the potential to add to this.