The clinimetric properties of the World Health Organization Disability Assessment Schedule II in early inflammatory arthritis

OBJECTIVE: To assess the clinimetric properties of a new health-related quality of life (HRQOL) instrument, the World Health Organization Disability Assessment Schedule II (WHODAS II), in patients with early inflammatory arthritis. METHODS: Internal consistency as well as criterion, construct, and discriminative validity of the WHODAS II were assessed in 172 patients with early inflammatory arthritis who completed the WHODAS II, the Medical Outcomes Study Short Form 36 (SF-36), and other measures of disease severity, functioning, pain, depression, and resource use. Test-retest reliability of the WHODAS II was assessed by having a subset of 20 patients complete the WHODAS II a second time, 1 week after the first assessment. RESULTS: The WHODAS II had high internal consistency (Cronbach's alpha = 0.96 for patients working or in school and 0.93 for patients not working or in school). Test-retest intraclass correlation coefficients of the WHODAS II total score and subscales ranged from 0.82-0.96. The WHODAS II total score was strongly correlated with the SF-36 physical component score (Kendall's tau-b 0.51, P < 0.001) and moderately correlated with the SF-36 mental component score (tau-b 0.43, P < 0.001). WHODAS II correlations with disease outcomes ranged from Kendall's tau-b 0.15-0.55. The WHODAS II significantly differentiated between every aspect of disease severity assessed with the exception of measures of health resource use. CONCLUSION: The WHODAS II is a valid and reliable measure of HRQOL in cross-sectional studies of patients with early inflammatory arthritis. Research is still required to investigate potential item redundancy and determine its usefulness in longitudinal studies.     

Clinical significant of serum chromogranin A levels for diagnosing pheochromocytoma in hypertensive patients

OBJECTIVE: CMA is a widespread glycoprotein located in the secretory vesicles of neuroendocrine cells and is co-released with peptides and biogenic amines into the circulation. The present study set out to investigate the clinical utility of assessing serum CGA levels in comparison with the urinary KTCO and their urinary metabolites concentrations, which are to date the gold standard validated diagnostic test. METHODS: From January 2000 to June 2001, 202 consecutive patients, aged 53 +/- 12.7, 102 males, were admitted to our department for a hypertension evaluation. Blood samples for measurements of plasma concentrations of chromogranin A were collected and serum CGA levels were quantified by RIA technique (RIACT). This radioimmunometric technique consisted in using 2 monoclonal antibodies directed to 2 specific antigenic domains of the middle portion of the CGA. The fixed threshold value for identifying positive results was, set at 100 ng/ml according to previous studies. RESULTS: No pheochomocytoma was diagnosed by conventional urinary KTCO essay. Of the 202 CGA blood samples, 32 turned out to be positive, due to commonly encountered false positive causes (inhibitor of the pump with protons, corticotherapy, hypergastrinemia, chronic renal insufficiency, respectively, in 11, 2, 1, 18 cases). The CGA plasma concentration averaged 77 +/- 77 mg/ml and 203 +/- 125 ng/ml in the CGA subgroup over the threshold value. CONCLUSION: The reliability of immunoradiometric serum CGA concentrations appeared according to this work to be comparable to that of the urinary KTCO levels and their urinary metabolites in hypertensives. Moreover, it solely requires a simple, easily done blood taking, less expensive than urinary KTCO collection. Besides, no antihypertensive drugs interfered with the analysis of CGA levels. However, some false positive results have to be mentioned in the presence of renal impairment, hypergastrinemia, corticotherapy, inhibitor of the pump with protons.     

Interferon-alpha and -beta differentially regulate osteoclastogenesis: role of differential induction of chemokine CXCL11 expression

In humans, type I interferon (IFN) is a family of 17 cytokines, among which the alpha subtypes and the beta subtype are differentially expressed. It has been suggested that IFN-beta activates a specific signaling cascade in addition to those activated by all type I IFNs. Nevertheless, no true biological relevance for a differential activity of alpha and beta IFN subtypes has been identified so far. Because type I IFNs are critical for the regulation of osteoclastogenesis in mice, we have compared the effect of IFN-alpha2 and IFN-beta on the differentiation of human monocytes into osteoclasts. Primary monocytes undergoing osteoclastic differentiation are highly and equally sensitive to both alpha2 and beta IFNs as determined by measuring the induction levels of several IFN-stimulated genes. However, IFN-beta was 100-fold more potent than the alpha2 subtype at inhibiting osteoclastogenesis. Expression profiling of the genes differentially regulated by IFN-alpha2 and IFN-beta in this cellular system revealed the chemokine CXCL11 as the only IFN-induced gene differentially up-regulated by IFN-beta. We show that recombinant CXCL11 by itself inhibits osteoclastic differentiation. These results indicate that autocrine-acting CXCL11 mediates, at least in part, the regulations of osteoclastogenesis by type I IFNs.     

Severe pulmonary hypertension and Takayasu arteritis

Takayasu arteritis is an inflammatory disease that affects large vessels, especially the aorta and its branches. The clinical features of the disease depend on which arteries are affected. Although pulmonary artery involvement is common, only rarely is this the main clinical manifestation. We describe the case of a young woman with dyspnea who had severe pulmonary hypertension secondary to Takayasu arteritis of the pulmonary artery. She was administered corticosteroid (methylprednisolone) and immunosuppressant (azathioprine) therapy and a stent was implanted in the left pulmonary artery. Both hemodynamic and clinical signs improved.     

Importance of measurements at or after the J-point for evaluation of ST-segment deviation and resolution during treatment for acute myocardial infarction

BACKGROUND: Determination of ST-segment deviation (STdev) and its resolution (STR) by reperfusion strategies have become important tools in the assessment of patients with acute myocardial infarction (AMI). STdev has been measured at different time-points, i.e. at 20-80 ms after the J-point. There are no data comparing STR at different time-points. METHODS AND RESULTS: STdev was measured using a new computer-assisted workflow. The intraclass correlation coefficients (ICC) for validity and agreement vs. classical manual measurements (n=1020) were both 0.996 (p<0.0001). The reliability indices were 0.991 (95% CI 0.990-0.992) for the manual vs. 0.995 (95% CI 0.995-0.996) for the computer-assisted method, indicating superiority of the latter. 12-lead STdev were determined on ECGs before (baseline) and 180 min after start of thrombolytic therapy, measured both at the J-point (STdev(J)) and 20 ms after the J-point (STdev(J20); n=2400). STdev(J20) was on average 0.01+/-0.03 mV higher than STdev(J) (p<0.0001) with a tendency towards larger differences for higher ST-elevations (p<0.001). Although the average STR calculated from STdev(J20) and STdev(J) was not statistically different in any infarct location group, in 26% of the patients the difference was >10%, and 11% of the patients were classified into another ST-resolution group. Analysing STdev only in the single lead with the highest ST-elevation at baseline (a simplified measurement which may eliminate the confounding effect of ST-depressions) showed an even higher classification discordance (14% of the patients). CONCLUSIONS: The time-point of STdev measurement is an important variable to be accounted for when evaluating ST resolution data. Uncontrolled extrapolation of classification schemes based on STdev(J20) to other time-points cannot be justified.     

Multidrug-resistant tuberculosis: case reports study in a central state of Brazil

Multidrug-resistant tuberculosis (MDR-TB) is an emerging and worrisome health problem that threatens tuberculosis (TB) control worldwide. The clinical management of MDR-TB is a complex issue associated with the use of multiple drugs for a long period, usually accompanied by side effects and high costs. The objective of this work was to relate cases of MDR-TB occurring in Goiás, a central state of Brazil. We related five cases of MDR-TB, three women and two men. All were pulmonary cases. Three were in their second treatment and two in their first treatment. Surgical pulmonary resection was performed in one case. One death occurred. Lack of adherence, gastric intolerance to anti-TB drugs and poor clinical management were the main aspects related to the emergent resistance. A revision of the main clinical aspects of this disease was performed.     

Early treatment of secondary hyperparathyroidism in moderate renal insufficiency: low-phosphorus diet versus calcium carbonate

Calcitriol deficiency and phosphorus retention are mechanisms involved in the pathogenesis of renal hyperparathyroidism. The aim of this study was to evaluate the effect of dietary phosphorus restriction versus calcium carbonate treatment for one month on PTH and calcitriol levels in patients with mild renal failure. We studied two groups of patients: Group I: 21 patients (14M/7F); mean age 61 years old; mean glomerular filtration rate 51 ml/min. Their diet contained phosphorus 700 mg/day. Group II: 30 patients (21M/9F); mean age 58; mean glomerular rate 56 ml/min. They were divided in two subgroups: 18 patients treated with calcium carbonate 2.5 g/day and 12 patients with 5 g/day. Serum PTH, calcitriol, 25(OH)D3, calcium, phosphorus and urinary excretion of calcium and phosphorus were measured before and after a 30 day period. The low phosphorus diet (Group I) resulted in a significant decrease in PTH levels (81.3 +/- 35 vs 71 +/- 39 pg/ml, p < 0.05) and significant increase in calcitriol levels (22.4 +/- 4.4 vs 33.4 +/- 7.5 pg/ml, p < 0.05). In our study calcium carbonate treatment (Group II) had no effect on PTH and calcitriol levels.     

Abnormal Ca2+ signalling in vascular endothelial cells from spontaneously hypertensive rats: role of free radicals

OBJECTIVE: To test the hypothesis that the Ca2+ signal transduction process in endothelial cells from genetically hypertensive rats (SHR) is affected by an overproduction of free radicals. METHODS: The Ca2+ response to the inositol 1,4,5-triphosphate (IP3) mobilizing agonist, ATP, was measured using the fluorescent probe, fura-2, in endothelial cells from Sprague-Dawley rats, and in young and age-matched genetically hypertensive rats (SHR). The effect of free radicals and reducing agents on the intracellular release of Ca2+ and IP3productionwas determined in resting and ATP-stimulated cells. Experiments were also performed to compare the level of expression and enzymatic activity of catalase and superoxide dismutase (SOD) in endothelial cells from SHR and Sprague-Dawley rats. RESULTS: The exposure of aortic endothelial cells from Sprague-Dawley rats to the free-radical generating system, hypoxanthine + xanthine oxidase (HX/XO), caused a time- and concentration-dependent inhibition of the ATP-induced Ca2+ response. A similar HX/XO-dependent inhibition was also observed in Sprague-Dawley cells stimulated with the endoplasmic reticulum Ca2+-ATPase inhibitor, thapsigargin. Incubation with the antioxidative enzymes, catalase and SOD, had no effect on the ATP-induced Ca2+ release in Sprague-Dawley cells, but led to a strong increase in the internal release of Ca2+ in cells from adult (12 weeks old) or young (3 weeks old) SHR. The effect of antioxidants was not related either to an enhancement of the ATP-induced production of IP3, or to a lower expression and activity of SOD and catalase. CONCLUSION: The present work provides evidence that the Ca2+ signalling process in SHR endothelial cells is affected by an overproduction of free radicals, resulting in a depletion of releasable Ca2+ from IP3-sensitive and insensitive Ca2+ pools. These results point towards a beneficial action of antioxidants on Ca2+ signalling in endothelial cells from models of hypertension.