Measurements of bone mineral density of the proximal femur by two commercially available dual energy X-ray absorptiometric systems.

Two dual energy X-ray absorptiometric (DXA) instruments have recently become commercially available for local bone densitometry: the QDR-1000 (Hologic Inc.) and the DPX (Lunar Radiation Corp.). We report the precision, influence of femoral rotation, correlation and agreement of bone mineral measurements of the proximal femur by these two instruments. In vitro (femur phantom) short-term precision was 1.1%-3.5%, and the long-term precision was 1.2%-3.8%. In vivo (groups of 10 premenopausal and 10 post-menopausal women) short-term precision of duplicate measurements was 1.6%-4.7%, and long-term precision was 1.9%-5.5%. Overall, the precision for Ward's triangle was over 3% and that for the femoral neck and trochanter, 2%-3%. Rotation of a femur phantom produced a statistically significant change in the bone mineral density (BMD) of the femoral neck. Within a clinically relevant range of femoral rotation (20 degrees inward rotation +/- 5 degrees) the coefficient of variation (CV%) increased by a mean factor of 1.1-1.4. Although the correlation (r less than 0.9) between BMD measurements of the proximal femur by the DPX and QDR-1000 in 30 postmenopausal women was high, there was lack of agreement between the two instruments. We found no statistically significant differences between the right and left femur in 30 postmenopausal women. A bilateral femur scan took a mean total time of about 22 min. We conclude that with the introduction of DXA instruments, the precision of bone mineral measurements of the proximal femur has improved. However, for comparability between commercially available DXA instruments, it might be advantageous if units were standardized.     

Changes in calcanean bone mineral occurring spontaneously and during hormone replacement therapy in early post-menopausal women.

The spontaneous calcanean bone loss occurring in healthy early post-menopausal women and the effect of two hormone replacement therapies (HRT's) were investigated in a longitudinal study. There was no difference between the right and left calcanean BMC or BMD (p > 0.15). The spontaneous bone loss was similar at all the skeletal sites measured, with a mean spontaneous loss in calcanean BMD of 1.6% over one year. Both HRT's significantly (p < 0.01) prevented the bone loss from all skeletal sites irrespective of the weight-bearing or content of trabecular bone, and (for the weight-bearing bones) there was even a gain in calcanean BMC and BMD and spinal BMD (p < 0.01). Bone mineral of the calcaneus and the spine correlated equally to body weight (r approximately 0.4, p < 0.001), whereas bone mineral in the forearm was not correlated to body weight. The correlations between the changes in bone mineral at the sites measured were all significant (r approximately 0.2-0.4).     

N-acetylcysteine modifies the acute effects of isosorbide-5-mononitrate in angina pectoris patients evaluated by exercise testing

Nitrates are well established in the treatment of angina pectoris and the presence of sulfhydryl groups seems to be fundamental to nitrate-induced vasodilatation. The present study was performed to elucidate if large oral doses of N-acetylcysteine (NAC, 2,400 mg X 2), a donor of sulfhydryl groups, given together with a single oral dose of the long-acting nitrate, isosorbide-5-mononitrate (5-ISMN, 60 mg), would modify the nitrate effect evaluated by exercise testing before and after additional sublingual doses of nitroglycerin (NTG). Ten patients with angina pectoris and angiographically proven significant coronary artery disease were included. All patients received a baseline therapy with beta blockers. None of the patients had developed nitrate tolerance at inclusion. NAC/5-ISMN treatment significantly prolonged the total exercise time as compared with placebo/5-ISMN (7.7 +/- 2.1 min vs. 6.8 +/- 1.7 min, p less than 0.05). This increase was of such magnitude that no further effect was obtained after additional NTG doses. This study demonstrated that increased availability of sulfhydryl groups can increase the exercise capacity in angina pectoris patients treated with 5-ISMN without nitrate tolerance.     

Circulating neutrophil CD14 expression and the inverse association of ambient particulate matter on lung function in asthmatic children.

BACKGROUND: Identifying baseline inflammatory biomarkers that predict susceptibility to size-specific particulate matter (PM) independent of gaseous pollutants could help us better identify asthmatic subpopulations at increased risk for the adverse health effects of PM. OBJECTIVE: To evaluate whether the association between lung function and exposure to ambient levels of PM less than 2.5 microm in diameter (PM2.5) (fine) and 10 to 2.5 microm in diameter (PM(10-2.5)) (coarse) in children with persistent asthma differed across baseline measures of inflammation and innate immune activation. METHODS: We performed a panel study on a local population of 16 children with persistent asthma and evaluated daily pulmonary function (percentage of predicted peak expiratory flow and forced expiratory volume in 1 second) while concurrently measuring daily PM2.5 and PM(10-2.5) exposure from a central site in Chapel Hill, North Carolina. The children underwent a baseline medical evaluation that included assessment of several immunoinflammatory biomarkers in peripheral blood. RESULTS: Children without measurable CD14 expression on circulating neutrophils had significantly reduced pulmonary function (forced expiratory volume in 1 second and peak expiratory flow) with each interquartile range (IQR) increase in PM2.5 (IQR = 8.5 microg/m3) and PM(10-2.5) (IQR = 4.1 microg/m3) concentration, unlike children with measurable CD14 expression (P < .001 for interaction). CONCLUSIONS: Asthmatic children with muted surface expression of CD14 on circulating neutrophils may have a decreased capacity to respond to bacterial components of PM.     

High-dose inhaled steroids in the management of asthma A comparison of the effects of budesonide and beclomethasone dipropionate on pulmonary function, symptoms, bronchial responsiveness and the adrenal function

Svendsen UG, Frølund L, Heinig JH, Madsen F, Nielsen NH, Weeke B. High-dose inhaled steroids in the management of asthma. A comparison of the effects of budesonide and beclomethasone dipropionate on pulmonary function, symptoms, bronchial responsiveness and the adrenal function.
The efficacy of budesonide (800 μg b.d.) and beclomethasone dipropionate (750 μg b.d.) in controlling the symptoms of asthma, pulmonary function, bronchial responsiveness to histamine, and adrenal function, was assessed in a double-blind, double-dummy cross-over study of 36 adult chronic asthmatic patients. The patients, the majority of whom were assessed to be affected to a severe degree, were insufficiently controlled in their current regimen of inhaled steroids and/or inhaled and oral bronchodilators. A 2 weeks baseline period preceded 6 weeks of treatment with each of the study drugs. Both treatment groups showed improvements from baseline in clinical assessment of lung function carried out after the first 6 weeks of treatment. No significant differences were seen throughout the entire 12 weeks study, when comparing the effects of the treatments on FEV₁ FVC, PEF or the histamine PC₂₀. Asthma severity, symptom score and inhaled bronchodilator use showed the same results after both treatments. It is concluded that inhalations of budesonide and beclomethasone dipropionate in high doses are equally potent in the treatment of severe asthma. There is no significant influence on the adrenal function and no significant side effects during a period equal to that of the present study.     

Human skin fibroblast in vitro tetraploidy. Flow cytometric DNA assay used to confirm metaphase assay in patients with various colonic diseases

One hundred twenty-two patients with various colon pathologies (43 colorectal carcinoma patients exclusive of the known autosomal dominant colorectal cancer syndromes, 31 patients with solitary colorectal adenomas, 27 patients with ulcerative colitis, and 21 controls with no evidence of colorectal cancer) were investigated for in vitro tetraploidy in dermal fibroblasts cultures using a metaphase assay for determination of numerical chromosomal alterations. Later, stationary cultures of these skin fibroblasts were investigated with DNA flow cytometry. There was good correlation between the percentage of tetraploid metaphase cells and the percentage of nuclei with a flow cytometric DNA index of 2. Using a linear discrimination function to classify the flow cytometric data, the peak with DNA index of 2 was the most important parameter, supplemented by the region with DNA index greater than 2, whereas the region with DNA index between 1 and 2 probably represented a different subpopulation. We have thus demonstrated that only the region with a DNA index of 2 or greater is suitable in determining in vitro tetraploidy in stationary skin fibroblast cultures.     

Long QT syndrome with a high mortality rate caused by a novel G572R missense mutation in KCNH2

In a four-generation family with long QT syndrome, syncopes and torsades de pointes ventricular tachycardia (TdP) were elicited by abrupt awakening in the early morning hours. The syndrome was associated with a novel KCNH2 missense mutation, G572R, causing the substitution of a glycine residue at position 572, at the end of the S5 transmembrane segment of the HERG K(+)-channel, with an arginine residue. This segment is involved in the channel pore and the mutation may cause a reduction in the rapidly activating delayed rectifier K+ current (Ikr), or changed gating properties of the ion channel, leading to prolonged cardiac repolarization. The electrocardiograms of affected persons showed prolonged QT interval and notched T waves. Despite treatment with atenolol, 200 mg twice daily, the proband still experienced TdP episodes. Three untreated relatives of the proband died suddenly, and unexpectedly, at 18, 32, and 57 years of age. The G572R mutation is thus associated with a high mortality rate, and the clinical presentation illustrates that some mutations may not be controllable by just beta-blockade.