Plethysmographic and biochemical markers in the diagnosis of endothelial dysfunction in pediatric acute lymphoblastic leukemia survivors - new applications.

Acute lymphoblastic leukemia (ALL) and its treatment are associated with endothelial dysfunction (ED) and increased cardiovascular risk in adulthood. There are no data on ED in children after successful treatment of ALL. We aimed to assess new ED in these children using the plethysmographic reactive hyperemia index (RHI) and biomarkers that are known to be related to ED. In all, 22 children (mean 15.6 years), after successful treatment of ALL, and 18 healthy subjects were included in this prospective study. RHI, plasma concentrations of asymmetric dimethyl arginine (ADMA), high-sensitive CRP (hsCRP) and E-selectin were measured in all children. RHI values were significantly lower in ALL patients when compared with healthy controls (p<0.05). hsCRP was significantly increased in ALL patients compared with the control group (p<0.001). E-selectin plasma levels were higher in ALL patients as compared to healthy controls (p=0.05). This is the first study that combines both plethysmographic and biochemical methods to assess ED in ALL survivors. Significantly decreased RHI with elevated plasma concentrations of biochemical markers imply a possible association with premature ED in ALL patients. The combined diagnostic approach seems to be a valuable tool for more accurate detection of ED and preventive cardiovascular management in these patients.

How to interpret elevated plasmatic level of high-sensitive troponin T in newborns and infants?

Research and clinical implications on novel cardiac biomarkers has intensified significantly in the past few years. The high-sensitive troponin T (hscTnT) assay plays a dominant role in diagnostic algorithm regarding myocardial injury in adults. Despite generally accepted use of hscTnT there are no data about physiological concentrations and cut-off limits in neonates and infants to date. The aim of this study is to assess hscTnT levels in healthy newborns and infants. Consecutively 454 healthy full termed newborns and 40 healthy infants were enrolled in the study. Samples of cord or venous blood were drawn and tested for hscTnT concentrations with high-sensitive TnT assay (Roche Cobas e602 immunochemical analyzer). The 97.5 percentile of hscTnT concentration was assessed and correlation analysis was performed in neonates. Two hundred and thirteen samples (47 %) were excluded due to blood hemolysis of various degrees in neonates. Finally, the group of 241 healthy newborns was statistically analyzed. The median concentration of hscTnT was 38.2 ng/ml, 97.5 percentile reached 83.0 ng/l (confidential interval 74.1 to 106.9 ng/l). HscTnT concentrations were statistically decreased in hemolytic samples when compared to non-hemolytic samples (34.3 ng/l [26.7 to 42.0 ng/l] and 37.1 ng/l [30.5 to 47.9 ng/l], respectively, p=0.003). Elevated plasma concentrations of hscTnT decreased to adult level within six months. This study has confirmed the higher reference levels of hscTnT in neonates and young infants when compared with adult population. Many extracardiac factors as hemolysis and age may affect the hscTnT level. Based on presented results, a careful clinical interpretation of hscTnT is recommended.

Gut peptide hormones and pediatric type 1 diabetes mellitus.

The aims of our study were to evaluate plasma levels of gut hormones in children with Type 1 diabetes mellitus (T1DM) in comparison with healthy controls and to correlate plasma concentrations of gut hormones with blood biochemistry, markers of metabolic control and with anthropometric parameters. We measured postprandial levels of specific gut peptide hormones in T1DM children. Amylin, glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide 1 (GLP-1), ghrelin, leptin, pancreatic polypeptide (PP), and polypeptide YY (PYY) were assessed in 19 T1DM children and 21 healthy reference controls. Multiplex assay kit (LINCOplex(®)) was used for determination of the defined plasma hormone levels. T1DM subjects had significantly reduced amylin (p<0.001) and ghrelin (p<0.05) levels, whereas GIP (p<0.05) was elevated when compared with healthy controls. Plasma levels of other measured hormones did not differ statistically between the studied groups. Further analysis of T1DM patients demonstrated an association between body mass index and GLP-1 (r=0.4642; p<0.05), leptin (r=0.5151; p<0.05), and amylin (r=0.5193; p<0.05). Ghrelin levels positively correlated with serum HDL cholesterol (r=0.4760; p<0.05). An inverse correlation was demonstrated with triglycerides (TG) (r= -0.5674; p<0.01), insulin dosage (r= -0.5366; p<0.05), and HbA1c% (r= -0.6864; p<0.01). Leptin was inversely correlated with TG (r= -0.6351; p<0.01). Stepwise regression analysis was performed to enlighten the predictive variables. Our study demonstrated an altered secretion pattern of gut peptide hormones in T1DM children. A close correlation was revealed between these peptides as well as with blood biochemistry, markers of metabolic control and with anthropometric parameters. Further studies are essential to explore this issue in T1DM children.

Fludarabine and melphalan-based conditioning for patients with advanced hematological malignancies relapsing after a previous hematopoietic stem cell transplant.

Severe regimen-related toxicity often complicates second transplant procedures performed in patients with hematological malignancies that have relapsed after an initial hematopoietic stem cell (HSC) transplant. Therefore, we studied the safety and efficacy of a reduced-intensity fludarabine and melphalan based conditioning regimen in 11 patients who had relapsed following an autologous (n = 7) or allogeneic (n = 4) HSC transplant. All patients received allogeneic peripheral blood HSC from either an HLA-identical (n = 7) or an HLA-mismatched (n = 4) relative. Diagnoses included AML (n = 9), ALL (n = 1), or Hodgkin's disease (n = 1). Only one patient was in complete remission at the time of second transplant. The median interval between first transplant and relapse was 163 days (range 58-1885). Recipients of HLA-mismatched transplants received antithymocyte globulin in addition to fludarabine and melphalan as part of the conditioning regimen. All 11 patients received acute GVHD prophylaxis consisting of tacrolimus and methotrexate. Ten of 11 patients achieved hematopoietic engraftment with a median time to absolute neutrophil count >0.5 x 10(9)/l and to platelet count of >20 x 10(9)/l of 14 and 19 days, respectively. All engrafting patients achieved 100% donor chimerism on initial analysis, except for one with persistent leukemia at day +19. Two patients experienced grade 3 regimen-related toxicity, manifesting as acute renal failure. Acute GVHD grades 2-4 occurred in two recipients and chronic GVHD in four. The 100-day mortality from all causes was 36%. Ten of 11 patients (91%) died a median of 140 days (range 9-996) after the second transplant. The causes of death included relapse (n = 5), sepsis (n = 4), and idiopathic pneumonia syndrome (n = 1). One patient with AML survives in remission at 880 days post-transplant. We conclude that fludarabine- and melphalan-based conditioning promotes full donor chimerism, even following HLA-mismatched transplants. However, the regimen may be more beneficial when applied to patients undergoing allogeneic HSC transplantation earlier in their disease course.

An approximation of stenotic aortic valve area by phonomechanocardiographic method: the comparative study of noninvasive methods.

Phonomechanocardiographic and ultrasonocardiographic parameters were compared in the multiplex manner in order to assess a degree of narrowing of the stenotic aortic valve areas. Adult patients with aortic valve stenosis were included in the study. The main condition for admission in the research sample was that the mean rate of circumferential fibre shortening be greater than 1 s-1 i.e. "compensated" preejection period/ejection time ratio (PEP/LVET). The control group were persons as sample stratified from healthy population. A possibility of approximate assessment of valve areas in patients with aortic stenosis is rendered by inserting the phonomechanocardiographic parameters in the modified Gorlin and Gorlin formula, provided that values of the normalised ejection function index (PEP/LVET2) and the ejection-isovolumetric coefficient corrected for pulse transmission time (LVET/IVCT+PTT) are known. The phonomechanocardiographic indexes of the transvalvular aortic pressure gradient and normalised stroke volume correlate curvilinear. The value of the LVET/IVCT + PTT equal or greater than that extrapolated for the given PEP/LVET2 in our formula means critically stenotic aortic valve area below 0.8 cm2. The given approximation could be used as a noninvasive and nongeometric polycardiographic or phonomechanocardiographic pattern for assessing the degree of narrowing of aortic valve area. The aortic valve stenosis is an illness in which a lot is expected from noninvasive cardiologic parameters when a surgical indication is in question. A severe or tight aortic valve stenosis, which required a surgical treatment according to current views, existed when valve area is less than 0.8 cm2 or when the transvalvular aortic systolic pressure gradient is greater than 50 mm Hg or 6.67 kPa, but with normal cardiac index in the same time.(ABSTRACT TRUNCATED AT 250 WORDS)

Electrocardiographic and clinical anticipation of the left ventricular systolic function, systemic vascular resistance, and myocardial hypertrophy--normal values and validation of method in patients with arterial hypertension.

In order to study the hemodynamic effects of the antihypertensive drugs in patients with essential hypertension, systolic time intervals from ECG data were extrapolated. The study was performed in 36 healthy individuals and 38 patients with essential hypertension without a drug therapy and/or in the wash out period more than three weeks and after a treatment. The stroke volume (SV) was determined as a product of the ejection time (ET), the pulse pressure (PP) and the flow coefficient (Kf). The Kf was extrapolated from Doppler-cardiographic parameters and it significantly correlated with the normal diastolic blood pressure (TA(d)) if the QT is not prolonged and the electrical systole/mechanical systole ratio (QS2/MS) not disturbed: Kf = 9.356 e-0.008 TA(d); r = -0.9. In arterial hypertension the correlation was also curvilinear: kf = 3.962 e-0.001 TA(d); r = -0.99. The arteriolar stiffness was defined as the PP/SV ratio. The cardiac output (CO) and systemic vascular resistance (SVR) were determined according to conventional formulas by known clinical and extrapolated ECG data. The cardiac contractile or muscle performance was defined as corrected changes of the ejection function for the given afterload according to the formula: I (-0.004 TA(d) + PEP/ET) -0.014 x 100; the normal 95% confidence limits for the laboratory used are -6.6% to +6%. Systolic time intervals were extrapolated from ECG data in the consecutive manner: QS2 = kQS2 x QT, ET = kET x JT, and MS = kMS x ET. The correlation of kQS2 with QT is curvilinear: kQS2 = 2.760 e-2.732 QT.(ABSTRACT TRUNCATED AT 250 WORDS)

The left ventricular ejection time/filling period ratio as derived and simplified new index for noninvasive approximation of primary lusitropy disturbances in chronic hypertensive heart disease: a comparative Doppler-cardiographic and digital-echocardiographic study.

A theoretical new Doppler-cardiographic index was developed for a noninvasive approximation of primary lusitropy disturbances from the peak filling/peak ejection rate ratio. This simplified index, the left ventricular ejection time/filling period ratio was directly extrapolated from the outflow and inflow sample volumes. An index was significantly lower in a group of hypertensive patients with global relaxation disturbance than in the group with "partial" lusitropy disturbance. Between this index (x) and the isovolumetric relaxation period (y) there exists a very tight linear correlation: y = -124 x + 148; r = -0.89. All patients had a pressure overload left ventricular hypertrophy and therefore a prolonged protodiastolic period from the aortic valve closure to the mitral valve opening without a significant difference between the groups of patients. There were significantly higher values of the isovolumetric relaxation period and the standard and normalised first time derivatives of protodiastolic left ventricular dimension changes in the group of patients with global relaxation disturbances. There were determined confidence limits for the appearance of primary lusitropy disturbances on the basis of defined parameter changes, the left ventricular ejection time/filling period ratio, the isovolumetric relaxation period and the standard and normalised first time derivatives of protodiastolic dimension changes. One could conclude that the left ventricular ejection time/filling period ratio is a simple and easily derived index for the noninvasive approximation of primary lusitrophy and global relaxation disturbances in the pressure overload left ventricular hypertrophy.