Assessment of the Role of Urinary Heparanase in Lupus Nephritis Patients and Its Correlation with Disease Activity.

Assessing the activity of lupus nephritis (LN) with novel biomarkers is a promising noninvasive diagnostic tool for managing systemic lupus erythematosus (SLE). We assessed the ability of urinary heparanase to identify LN and its relation to the disease's activity. This crosssectional study had 90 subjects: 70 patients with SLE and 20 healthy controls. A full medical history, clinical examination, and routine investigations were carried out for the patients and controls. Immunological assays and assessments of the disease's activity with the SLE Disease Activity Index (SLEDAI) and the renal SLEDAI (r-SLEDAI) were carried out for LN groups. Urinary heparanase levels were measured using an enzyme-linked immunosorbent assay for all subjects. Of our patients, 20 had active LN, 17 had nonactive LN, 18 had active lupus without renal involvement, and 15 had nonactive lupus without renal involvement. The level of urinary heparanase was significantly higher in the LN groups than in the non-LN groups and the controls and was significantly higher in those with active LN than in those with nonactive LN. There were significant positive correlations between urinary heparanase and 24-h urinary protein, total SLEDAI, and r-SLEDAI, and significant negative correlations between urinary heparanase and Complements 3 and 4. Urinary heparanase predicted the activity of LN with a sensitivity of 80% and a specificity of 91.43%. Urinary heparanase levels were higher in patients with active LN and correlated with the markers of disease activity, indicating that it can serve as a useful new biomarker for the activity of LN.

Toll-like receptor 9 in systemic lupus erythematosus, impact on glucocorticoid treatment.

AIM: To assess TLR9 expression in systemic lupus erythematosus (SLE) patients, its correlation with disease activity, and impact of TLR9 expression on the response to oral glucocorticoids. METHODS: Twenty-five active SLE, 15 inactive, and 15 control subjects were included. Anti-DNA, ANA, C3, C4, and TLR9 mRNA expressions were assessed. Active SLE patients only received oral steroid for 6 weeks. Post therapy, they were classified into steroid sensitive and steroid resistant. Data were reassessed after treatment. RESULTS: SLEDAI, anti-DNA, ANA, and TLR9 expressions were significantly higher in active SLE patients. Based on retrograde analysis, TLR9 expression was significantly higher in steroid-resistant versus steroid-sensitive group before treatment, with no significant difference between them after treatment. There was a significant positive correlation between TLR9 expression and SLEDAI score and anti-DNA and negative correlation with C3 and C4 in all patients. CONCLUSION: TLR9 may play a role in the pathogenesis of SLE and correlates with the disease activity. Corticosteroids have no effect on TLR9 expression, explaining lack of corticosteroid response in some SLE patients. TLR 9 expression can be used in predicting glucocorticoid response in active SLE patients. New treatment modalities targeting TLR9 expression may be of value in steroid-resistant patients.

Detection of hepatopulmonary syndrome in patients with liver cirrhosis using 3D contrast echocardiography.

BACKGROUND AND STUDY AIMS: Hepatopulmonary syndrome (HPS) is characterised by the triad of advanced liver disease, arterial hypoxaemia and intrapulmonary vascular dilatation (IPVD). The present study aimed to evaluate HPS in patients with liver cirrhosis and the role of three-dimensional (3D) contrast echocardiography in the detection of this syndrome. PATIENTS AND METHODS: A total of 78 chronic liver disease patients aged 42 ± 11 years fulfilled the criteria for this study and were subjected to clinical examination, laboratory investigations, arterial blood gases measurement, pulmonary function tests, upper gastrointestinal endoscopy, 3D contrast echocardiography and computed tomography (CT) pulmonary angiography. RESULTS: According to 3D contrast echocardiography results, we divided the patients into a positive group (n=26) in which patients showed a delayed appearance of contrast in left heart chambers and a negative group (n=52). Among 26 patients of the positive group, nine had hypoxaemia (partial pressure of oxygen (PaO(2)) <70 mm Hg) and were diagnosed as having hepatopulmonary syndrome (HPS), the other 17 who had shown echocardiographic evidence of IPVDs but without hypoxaemia were diagnosed as having sub-clinical HPS. This study showed significant correlation between positive contrast echocardiography findings and duration of liver disease, Child score, cyanosis, clubbing, orthodeoxia, portal vein diameter, spleen size and oesophageal varices grades. No significant correlation was found between 3D contrast echocardiography findings and age, sex, spider naevi and pulmonary function tests. Multivariate logistic regression showed that cyanosis, clubbing, orthodeoxia, Child score and portal vein diameter are independent predictors of HPS. CONCLUSION: Cyanosis, clubbing and platypnoea-orthodeoxia are suggestive indicators of HPS, which can be easily detected by 3D contrast echocardiography which can replace the trans-oesophageal echocardiogram (TEE) in cirrhotic patients.

Clinical and biochemical predictors of increased carotid intima-media thickness in overweight and obese adolescents with type 2 diabetes.

OBJECTIVE: To identify the clinical parameters associated with increased carotid intima-media thickness (CIMT) in overweight and obese adolescents with type 2 diabetes. METHODS: We studied 27 patients (11 males) with type 2 diabetes. Criteria for selection were age (12-19 years), body mass index above the 95th percentile for age and gender, a positive family history of diabetes, normal or high C-peptide, and negative studies for islet cell antibodies. Age- and gender-matched healthy subjects were selected as the control group. Measurements of CIMT, lipid profile, hypersensitive C-reactive protein, hemoglobin A1C (HbA1C), and insulin resistance by homeostasis model of assessment (HOMA) were obtained for all participants. RESULTS: CIMT was higher in diabetic patients than in healthy subjects (0.68 ± 0.16 vs. 0.58 ± 0.1, p < 0.01). The range of HbA1C in the 15 patients with uncontrolled diabetes was 7.6-10.4 (mean: 8.9 ± 0.9). CIMT, HbA1C, systolic blood pressure, triglycerides, HOMA, and C-reactive protein were significantly higher in patients with uncontrolled than with controlled diabetes. In diabetic patients, CIMT correlated positively with body mass index (p < 0.001), duration of diabetes (p < 0.001), systolic (p < 0.001) and diastolic blood pressure (p < 0.01), HbA1C (p < 0.001), HOMA (p < 0.01), and C-reactive protein (p < 0.01). CONCLUSIONS: CIMT is increased in adolescents with type 2 diabetes. Poor glycemic control, HOMA, increased C-reactive protein, body mass index, duration of diabetes, and elevated blood pressure are associated with early atherosclerosis in these patients.

The impact of H. pyiori eradication on response to oral iron therapy in patients with iron deficiency anemia.

Infection with Helicobacter pylori has been associated with Iron deficiency anemia (IDA). We assessed the effect of eradication of H. pylori infection on response to oral iron treatment. Twenty patients with IDA of no obvious cause, unresponsive to oral iron therapy with positive gastric biopsy for H. pyJoril infection received sequential eradication therapy for 10 days followed by oral iron therapy. Treated patients were followed up at 6 weeks and 12 weeks post eradication to assess dynamic changes in hemoglobin, serum ferritin and transferrin saturation. While 65% of anemic H. pylori infected cases had pangpstritis, 35% had antral gastritis. In the antrum severe and moderate gastritis were found in 40% and 45% of cases, respectively. Hemoglobin and serum ferritin level correlated inversely with grade of gastritis (P <0.001). Improvement in hematological parameters and serum iron profile was observed 6 weeks and 12 weeks post successful H. eradication oral iron therapy. In conclusion, eradication of H. pylori infection enhances the response to oral iron supplementation in patients with refractory IDA. Screening and eradication of H. pylori should be a standard procedure for patients with IDA.

Tissue Doppler and strain rate imaging detect improvement of myocardial function in iron deficient patients with congestive heart failure after iron replacement therapy.

BACKGROUND: Iron deficiency may contribute to diminished exercise tolerance in patients with congestive heart failure (CHF) even in absence of anemia. The aim of this study was to evaluate the effect of correction of iron deficiency on functional capacity and myocardial function in patients with CHF. METHODS: We studied 40 patients with ejection fraction <40%, hemoglobin% >12 g/dL, serum ferritin <100 ug/L, and transferrin saturation <20%. Patients received 200 mg weekly doses of iron dextran complex until serum ferritin level was between 200 and 300 ug/L or transferrin saturation level was between 30% and 40%. Transthoracic echocardiogram, tissue Doppler imaging, peak systolic strain rate, and 6 minute walk test were performed before iron therapy and at 12-week follow up. Peak early diastolic myocardial tissue velocity (E'), peak late diastolic myocardial tissue velocity (A'), and peak systolic myocardial tissue velocity (S') were measured. RESULTS: There was a significant improvement of New York Heart Association functional class (3.0 ± 0.4 vs. 2.1 ± 0.3, P < 0.05) and 6minutes walk distance (322 ± 104 vs. 377 ± 76, P < 0.01) from rest to follow up, respectively. Ejection fraction did not change significantly (32 ± 8% vs. 34 ± 9%, respectively). There was a significant improvement of S'-wave (3.0 ± 0.8 cm/sec vs. 6.0 ± 1.2 cm/sec, P < 0.05), E/E' ratio (22 ± 3 vs. 13 ± 3, P < 0.05), and peak systolic strain rate (-0.72 ± 0.11/s vs. -1.09 ± 0.37/s, P < 0.05) from baseline to follow-up, respectively. CONCLUSION: Correction of iron deficiency improves functional class and walking distance in nonanemic iron deficient patients with systolic heart failure. Tissue Doppler and strain rate demonstrated a significant improvement of diastolic and systolic function after therapy despite lack of improvement of ejection fraction. (Echocardiography 2012;29:13-18).