Thrombocytosis in rheumatoid arthritis: JAK2V617F-positive essential thrombocythemia

Thrombocytosis is an important laboratory finding in rheumatoid arthritis (RA) and it has a correlation with disease activity. Janus kinase 2 valin 617 phenylalanine (JAK2V617F) mutation has gained importance in the diagnosis of myeloproliferative diseases recently. There is no published report in literature on the association between RA and JAK2V617F-positive essential thrombocythemia (ET). In this report, we present a JAK2V617F-positive ET case that had RA. A 57-year-old male patient was diagnosed with RA according to the criteria of American College of Rheumatology (ACR), whose complaint was of pain in the hands and morning stiffness lasting for about 2 h. The patient was evaluated for thrombocytosis because he was in remission and suffering persistent thrombocytosis under treatment. After excluding the causes of secondary thrombocytosis, bone marrow aspiration and biopsy was performed. On peripheral blood and bone marrow PCR examination, the patient was detected to be JAK2V617F positive heterozygously and diagnosed with ET. As a conclusion, mild–moderate thrombocytosis is frequent in RA; however, ET can be diagnosed by JAK2V617F evaluation in peripheral blood in thrombocytosis, especially when platelet count is more than 1 million/ml and when persisting thrombocytosis is detected in RA remission.     

New insights into mechanisms of action of carvedilol treatment in chronic heart failure patients--a matter of time for contractility

BackgroundIt is unclear whether improvement in left ventricular (LV) ejection fraction (LVEF) following treatment with a combined α₁,β₁,β₂-blockade can be attributed to improvement in LV contractility, to a reduction in afterload, and/or to improvements in LV remodeling and chamber size. We aimed to examine whether the observed improvement in LVEF following carvedilol treatment is due to changes in intrinsic myocardial contractility beyond changes in LV chamber size or loading conditions.Methods and ResultsIn 49 consecutive patients with chronic heart failure (HF), LVEF ≤35%, NYHA functional class II–IV, on angiotensin-converting enzyme inhibitors but not on ß-blockers, LV contractile performance and remodeling were assessed by comprehensive echocardiography at baseline and after 3 and 6 months of treatment with carvedilol. Carvedilol treatment resulted in significant improvements in LVEF, shortening fraction, and velocity of circumferential shortening (VCF_c). There were no significant changes in the mean arterial blood pressure or systemic vascular resistance index; but LV end-systolic wall stress (LVESS), effective arterial elastance, ventriculoarterial coupling, and LV end-diastolic and end-systolic dimensions and volumes were significantly reduced. Estimated end-systolic elastance, VCF_c-to-LVESS ratio, and pulsatile arterial compliance significantly improved after 6 months of treatment with carvedilol. The slope of the VCF_c relationship to LVESS worsened from 0 to 3 months, but significantly improved from 3 to 6 months.ConclusionsDespite an initial transient negative inotropic effect from 0 to 3 months, carvedilol treatment was associated with a positive inotropic effect with significant improvement in load-independent indexes of myocardial contractility beyond what can be attributed to changes in LV chamber size and load after 3 months. There were no changes in systemic vascular resistance with carvedilol treatment; however, improvement in pulsatile arterial compliance and ventriculoarterial coupling suggested enhanced cardiac mechanoenergetic performance along with improved systemic arterial compliance.     

The Relationship between the VEGF Levels and VEGF mRNA Expression and Clinical Course in Different Glomerulonephritis

In this study, serum and urinary VEGF levels and VEGF expression in PBMNC were correlated with daily proteinuria, renal function tests, and renal histopathologic findings in untreated patients with different glomerulonephritis and with the course of renal function and proteinuria for one year. Forty-five untreated patients with different glomerulonephritis and 11 healthy persons comprised the study and control groups, respectively. VEGF mRNA expression was detected by RT- PCR in peripheral blood mononuclear cells (PBMNC), and VEGF levels were measured by ELISA in serum and urine samples simultaneously. Male/female ratio was 24/21 and mean ages were 34.49 ± 14.98. Serum and urinary VEGF levels, VEGF expressions in PBMNC, and the ratios of urine VEGF/urine creatinine were found to be similar in patients and controls. There were important correlations between urinary VEGF levels and baseline serum Cr (p = 0.035) and ESR (p = 0.022). There was also a marginal correlation between urinary VEGF levels and baseline CCr (p = 0.072). There was no correlation between serum and urinary VEGF levels and PBMNC mRNA expression and pathological findings such as with or without glomerular sclerosis, tubulointerstitial fibrosis (TIF), periglomerular fibrosis, and mesangial cell proliferation in renal biopsy. Serum and urinary VEGF levels or VEGF expression in PBMNC in patients with renal amyloidosis or proliferative or nonproliferative glomerulonephritis were similar with that of healthy controls and each other. Serum and urinary VEGF levels and PBMNC VEGF mRNA expression in untreated patients with different glomerulonephritis and controls were similar. We found only one important correlation, that between urinary VEGF levels and baseline serum creatinine levels in patients with different glomerulonephritis. Urinary VEGF can be an important pathogenesis of glomerular disease or a simple proteinuria. Serum and urinary VEGF levels and PBMNC VEGFmRNA did not change by periglomerular sclerosis, periglomerular fibrosis, or tubulointerstitial fibrosis on renal biopsy. PBMNC VEGF mRNA expression decreased in patients undergoing remission. In addition to the important correlation between urinary VEGF and serum creatinine, we also found an important correlation between erythrocyte sedimentation rate and urinary VEGF. This finding was interesting because we could not find a similar conclusion in other studies.