Plasma mid-regional proadrenomedullin level in children with pulmonary hypertension associated with CHD.

Adrenomedullin has been shown to inhibit proliferation in pulmonary artery smooth muscle cells and to alleviate pulmonary artery collagen accumulation in pulmonary hypertension. We aimed to assess mid-regional proadrenomedullin level in children with pulmonary hypertension due to CHDs. The current study was conducted in the Pediatric Cardiology Unit, Tanta University Hospital, on 50 children with CHDs: twenty-five patients had a complication of pulmonary hypertension and the other 25 patients without pulmonary hypertension. Another 25 children without CHDs were concluded as a control group. We performed complete history taking, full clinical assessment, chest X-ray, electrocardiogram, and echocardiographic assessment. Plasma level of mid-regional proadrenomedullin was assessed using a sandwich enzyme-linked immunosorbent assay test. Our results showed that the mean plasma level of mid-regional proadrenomedullin was significantly increased in patients with pulmonary hypertension. Significant positive correlation was found between mid-regional proadrenomedullin and mean pulmonary artery pressure. The best cut-off point of mid-regional proadrenomedullin as a diagnostic biomarker to discriminate patients with CHDs complicated with pulmonary hypertension was 199.22 nmol/l. Mid-regional proadrenomedullin significantly increased in patients with pulmonary hypertension who died as compared to patients who survived, with the best cut-off point was 428,8 nmol/l. We concluded that plasma levels of mid-regional proadrenomedullin were significantly elevated in children with pulmonary hypertension complicated by the CHDs. It could be used as a cardiac biomarker in these patients, with good diagnostic and prognostic value.

Diagnostic and predictive values of plasma connective tissue growth factor in children with pulmonary hypertension associated with CHD.

OBJECTIVE: To evaluate the diagnostic and predictive values of plasma connective tissue growth factor in children with pulmonary hypertension (PH)-related CHD. PATIENTS AND METHODS: Forty patients with PH-related CHD were enrolled as group I, and 40 patients with CHD and no PH served as group II. Forty healthy children of matched age and sex served as a control group. Echocardiographic examinations and plasma connective tissue growth factor levels were performed for all included children. Cardiac catheterisation was performed for children with CHD only. RESULTS: Plasma connective tissue growth factor levels were significantly higher in children with PH-related CHD compared to CHD-only patients and to control group and this elevation went with the severity of PH. There was a significant positive correlation between connective tissue growth factor levels and mean pulmonary pressure, pulmonary vascular resistance, and right ventricular diameter. A significant negative correlation was noticed between connective tissue growth factor levels, oxygen saturation, and right ventricular diastolic function. The sensitivity of plasma connective tissue growth factor as a diagnostic biomarker for PH was 95%, and the specificity was 90% at a cut-off value ≥650 pg/mL. The predictive value of plasma connective tissue growth factor for adverse outcome had a sensitivity of 88% and a specificity of 83% at a cut-off value ≥1900 pg/mL. CONCLUSION: Connective tissue growth factor is a promising biomarker with good diagnostic and predictive values in children with PH-related CHD.

Role of plasma asymmetric dimethyl-L-arginine levels in detection of pulmonary hypertension in children with CHD.

OBJECTIVES: The objectives of this study were to evaluate the plasma levels of asymmetric dimethyl-L-arginine in children with pulmonary hypertension due to CHD before and after treatment with sildenafil and to evaluate its diagnostic and prognostic value as a biomarker in such children. METHODS: A total of 60 children with CHD and 30 healthy control children matched for age and sex were recruited. Children with CHD were divided into two equal groups: the normal pulmonary pressure group (n=30) and the pulmonary hypertension group (n=30). Children with pulmonary hypertension were treated with sildenafil and were followed up for 6 months. Clinical data, haemodynamic parameters, echocardiographic examination, and asymmetric dimethyl-L-arginine levels were evaluated before and after treatment. RESULTS: Asymmetric dimethyl-L-arginine levels were significantly higher in patients with pulmonary hypertension than in those with CHD-only or the control group, and this increase was positively correlated with increased severity of pulmonary hypertension. Asymmetric dimethyl-L-arginine levels, mean pulmonary artery pressure, and pulmonary vascular resistance were significantly decreased after treatment with sildenafil. Moreover, asymmetric dimethyl-L-arginine level was significantly lower in patients who responded to sildenafil treatment compared with those who did not. At a cut-off point of more than 0.85 nmol/ml, asymmetric dimethyl-L-arginine has a sensitivity of 83% and a specificity of 80% to diagnose pulmonary hypertension-CHD. Asymmetric dimethyl-L-arginine has a sensitivity of 100% and a specificity of 94% to predict poor prognosis in pulmonary hypertension-CHD children at a cut-off point of 1.3 nmol/ml. CONCLUSION: Asymmetric dimethyl-L-arginine level has a good diagnostic and prognostic value as a biomarker in children with pulmonary hypertension-CHD and can be used for following up patients with pulmonary hypertension and predicting response to treatment.

Evaluation of the coronary circulation and calcification in children on regular hemodialysis.

BACKGROUND: The objective of this study was to evaluate the coronary circulation and calcification in children with end-stage renal disease (ESRD) on hemodialysis. METHODS: A total of 50 children with ESRD and 50 healthy controls were enrolled in the study. Cardiac functions and coronary blood flow were evaluated with conventional and tissue Doppler echocardiography. Coronary artery calcification (CAC) was evaluated using high-resolution multidetector computed tomography (CT). RESULTS: The hyperemic coronary flow volume (CFV) and coronary flow reserve were significantly lower in the patient group than in the controls, while there was no significant difference in the baseline CFV between the two groups. Hypertension was present in 60% and CAC was observed in 20% of the children in the patient group. CAC was present in 30% of the children in the hypertensive subgroup. The left ventricle myocardial performance index (LV MPI), CAC score, duration of hypertension and level of diastolic blood pressure were independent predictors of the coronary blood flow, and LV MPI, serum parathyroid hormone, duration of dialysis and E'/A' mitral valve were independent predictors of coronary calcification. CONCLUSION: High diastolic blood pressure, long duration of hypertension, high LV MPI and increased CAC scores are independent risk factors for impaired coronary blood flow in children with ESRD.

The role of hepatic expression of STAT1, SOCS3 and PIAS1 in the response of chronic hepatitis C patients to therapy.

BACKGROUND: The underlying mechanisms of hepatitis C virus (HCV) resistance to treatment are unknown. Signal transducers and activators of transcription (STAT) proteins play a critical role in antiviral defense. OBJECTIVE: To explore some of the mechanisms of HCV resistance to interferon, the expression of STAT1 and its negative regulators, protein inhibitor of activated STAT (PIAS1) and suppressor of cytokine signalling (SOCS3), in liver tissues of both inteferon responders and nonresponders in chronic HCV patients. METHODS: Sixty patients were divided into the following groups: group 1a comprised 38 treatment-responder chronic HCV patients; group 1b consisted of 22 treatment-nonresponder chronic HCV patients; and group 2 consisted of six control subjects. Liver biopsies were examined for histological scoring; STAT1, SOCS3 and PIAS1 expression was analyzed using Western blotting methods. RESULTS: STAT1 expression in the liver tissue of patients in group 1 was significantly increased compared with group 2 patients (P=0.001), while no significant difference in expression was observed between group 1a and group 1b patients (P=0.747). However, phosphorylated STAT1 protein was expressed at a significantly higher level in liver tissue of patients in group 1a compared with patients in group 1b (P=0.001). Western blot analysis of PIAS1 and SOCS3 protein expression in liver tissues from groups 1 and 2 revealed significantly increased expression in group 1 compared with group 2 (P=0.001). In addition, PIAS1 and SOCS3 protein expression was significantly higher in the liver tissues of patients in group 1b compared with patients in group 1a. CONCLUSION: Levels of STAT1 and/or the protein expression of its negative regulators, PIAS1 and SOCS3, may be a good predictor of response to therapy. These could be used as biomarkers that are easily detected by Western blotting or immunostaining during standard histopathological liver biopsy analysis.

Assessment of leukemia inhibitory factor and glycoprotein 130 expression in endometrium and uterine flushing: a possible diagnostic tool for impaired fertility.

BACKGROUND: Uterine receptivity and implantation are complex processes requiring coordinated expression of molecules by zygote and uterus. Our objective was to evaluate the role of the endometrial expression of leukemia inhibitory factor (LIF) and its glycoprotein 130 (gp130) receptor molecules and their secretion in uterine flushing during the window of implantation in cases of primary unexplained infertility CASE PRESENTATION: The study was conducted on 25 infertile women with unexplained infertility for at least two years and 10 normal fertile women as a control group . Endometrial tissue and uterine flushing were obtained. Each tissue specimen was divided into two pieces; one piece was used for histological dating of the endometrium and for immunostaining of progesterone receptors, and the second was used for RNA extraction and PCR assay of LIF and gp130 mRNA expression. Serum estrogen and progesterone were measured for all subjects. LIF mRNA was expressed in the endometrium of all normal fertile women but significantly decreased in infertile women. LIF was not detectable in 88% of infertile women while it was fairly detectable in 12% of them. Gp130 mRNA was hardly detectable in both fertile and infertile women with no difference between them. Infertile women secreted significantly less LIF and gp130 molecules in the uterine flushing compared with normal fertile women. CONCLUSIONS: Expression of LIF mRNA in endometrium could be used as a molecular marker of unexplained infertility. Assessment of secreted LIF and gp130 molecules in uterine flushing could be another useful and safe method for predicting successful implantation as well as for diagnosing and eventually treating women with impaired fertility using recombinant human LIF.

TNF-alpha and CXCL-10 correlation with insulin resistance in patients with chronic hepatitis C virus infection.

There are increasing reports of association between HCV infection and type-2 diabetes mellitus. Although the mechanism by which this association remains uncertain, development of insulin resistance may explain this association. We investigated the association of TNF-alpha and CXCL-10 with insulin resistance in HCV infected patients. Forty-four non-diabetic chronic hepatitis C patients and twenty healthy individuals were included. Fasting blood was used for glucose and insulin measurements. Diagnosis of insulin resistance (IR) was based on a mathematical means by the homeostasis model assessment score-insulin resistance index (HOMA-IR). Serum insulin, TNF-alpha and CXCL-10 levels were measured by enzyme linked immunosorbent assay (ELISA). Quantitative measurement of hepatitis C virus was performed by a standardized real time PCR assay. The HCV patients demonstrated a significant increase in serum TNF-alpha, CXCL-10, and HOMA-IR values as compared to normal controls. HOMA-IR level positively correlated with hepatitis C viral load, TNF-alpha and CXCL-10. It is concluded that, TNF-alpha, CXCL-10 correlate with IR and may play a role in the development of type-2 diabetes mellitus in chronic hepatitis C infected patients.

Effects of dexamethasone on pulmonary and renal functions in patients undergoing CABG with cardiopulmonary bypass.

UNLABELLED: This study evaluates whether dexamesathone in patients undergoing CABG using CPB results in better renal and pulmonary outcome. METHODS: 100 patients were randomized to receive either placebo or dexamethasone (1 mg/ kg, at induction of anesthesia and 0.5 mg/kg 8 h later). RESULTS: The differences regarding pulmonary parameters over times were significant in relation to measurements taken 10 minutes after intubation within groups; nevertheless, differences were significant between groups only at 12, 24 hours for A-a O(2) gradient, respiratory index, PaO(2)/FiO(2) ratio. Dexamethasone had no effect on extubation time. Creatinine clearance, urinary micro albumin excretion and (NAG) levels were comparable in both the groups. The dexamethasone treated patients were more likely to have hyperglycemia. CONCLUSIONS: Dexamethasone offers no renal protective effect and the drug is associated with significant improvement in A-a O(2) gradient, respiratory index, PaO(2)/FiO( 2) at 12, 24 hours postoperatively and had no effect on extubation time and lung compliance.