Apoptosis and oxidative stress in b thalassemia major in children

In B thalassemia the synthesis of beta globin chains is decreased .This interferes with the assembly of normal Hb A,. Recently apoptosis has been noted to play a central role in regulation of hemopieosis. Excess iron could generate reactive oxygen species [ROS] that may be involved in turn in lie damage of cellular compartment adding to apoptosis . The aim of this work is to study apoptosis and oxidative stress in B thalassemia major in children and their relationship to the severity of the disease and to the use of chelation . A cross sectional study of 56 patients with B thalassemia major aged 8 M -13 y as well as 10 apparently healthy age and sex- matched control . Beside full history and examination all patients and controls had the following investigations done Hb, serum ferritin, ALT, AST, ALP, FAS, TBARS and DNA damage measurement. Correlation studies showed that fas and TBARS showed significant negative correlation with Hb and significant positive correlation with ferritin . Newly diagnosed patients [First admission] showed significantly less severe DNA damage than recurrent cases . Chelated patients scored significantly better lhan non chelated patients . Patients on chelation showed significant better outcome regarding apoptosis and oxidative stress, therefore we must be ready with early chelation in all B thalassemia cases

effect of aminophylline versus milrinone on ischemia-reperfusion myocardial injury during open heart surgery

Cardioplegic arrest during cardiopulmonary bypass [CPB] is essential for the majority of cardiac surgical procedures; Cardioplegia protects the myocardium by providing continuous or intermittent oxygen while simultaneously reducing cardiomyocyte oxygen demand, but it does not inherently increase the ischemic-reperfusion injury tolerance of the cardiomyocytes. Aminophylline and milrinone by their phosphodiesterase inhibitor and anti-inflammatory activity may decrease this type of injury. This study has been designed to compare between the protective effect of aminophylline and milrinone over the heart during open heart surgery for valve replacement with CPB. Sixty adult patients undergoing elective single valve replacement were randomized to receive aminophylline 5 mg/kg [n=20], milrinone 50 microg/kg [n=20], or normal saline as control group [n=20] through intravenous infusion 10 minutes before the aortic cross-clamping. The cardiac troponin I, inotrope score, duration of mechanical ventilation, and length of ICU stay and other hemodynamic variables were measured and recorded. There were no differences between the three groups with regard to clinical variables. Cardiac troponin I raised significantly after declamping in the three groups, however it was significantly lower in aminophylline and milrinone group compared to control group immediately after CPB and after 8 hours with no significant differences between aminophylline and milrinone group, inotrope score duration of mechanical ventilation and length of ICU stay showed no significant differences between the three groups. Administration of aminophylline or milrinone reduces the subclinical myocardial injury with no difference between both agents and with no effect on the hemodynamic parameters or short term clinical outcome in patients undergoing single valve replacement with CPB

Adipocytokines in pre-pubertal children with type 1 diabetes: relation to some risk factors

Adipose tissue represents an active endocrine organ secreting a variety of factors that regulate energy metabolism and insulin sensitivity. The aim of this study is to evaluate adipocytokines in pre-pubertal children with type I diabetes mellitus and its relation to some risk factors. The study included 20 cases newly diagnosed with type 1 diabetes, 30 cases with long duration of diabetes, and 20 healthy matching children as controls. Cases and controls were subjected to full history taking and physical examination, estimation of BMI, blood glucose level and glycated hemoglobin. Non fasting blood samples were withdrawn from all cases and controls for estimation of serum adiponectin, resistin, leptin, TNF-alpha and IL-6. Results showed that newly diagnosed cases with type I diabetes had significantly lower BMI, serum adiponectin, and serum leptin levels and had significantly higher levels of TNf-alpha and lL-6 than cases with long duration of diabetes. No significant difference in resistin levels was observed between either studied cases or controls. Significant negative correlations were found between adiponectin with both lL-6 and TNF alpha serum levels in the whole studied cases. Also a positive correlation was found between resistin levels and duration of illness. In conclusion adipocytokines may play a role in metabolic adaptation of type I diabetes

Effect of haemodilution by intravenous crystalloids on coagulation system in surgical breast cancer patients

Aside from the efficacy of a specific solution, possible side-effects have become an increasing concern. One of the most important issues for assessing the optimal intravascular volume replacement strategy is the influence on the haemostatic process and subsequent influence on bleeding or the development of thrombosis. The aim of our study is an assessment of the effects of intravenous fluid administration especially crystalloids during operation in a progressive manners [progressive haemodilution] on coagulation system in cancer patients [breast cancer]. 36 female patients scheduled for breast cancer surgery above 18 years, weight ranged from 50-70 kg, ASA physical state I or II were included in the study and exclude all anaemic patients, patients with abnormal preoperative coagulation data. Patients were divided into 3 groups according to degree of haemodilution depending upon their haemodynamic stability: Group A [12 patients]: volume infused to them up to 500 ml saline 0.9%, Group B[12 patients]: received 1000 ml and Group C[12 patients]: received 1500 ml. All patients received general anaesthesia and continuously monitored with ECG, central venous pressure [CVP], non invasive blood pressure and pulse oximetry in each group during the period of surgery and the first 24hours postoperatively. Blood samples taken before surgery, after induction of anaesthesia, after the end of fluid infusion, after surgery, 5 hours, 12 hours and 24 hours postoperatively and the following parameter was measured complete blood picture, prothrombin time, prothrombin concentration, International normalized ratio [INK], activated partial thrompolastin time [a PTT], fibrinogen, fibrin degradation product [FDP], factor VIII, antithrombin III [AT III] and thrombin antithrombin complex [TAT]. The present study demonstrate no significant difference in white blood cell count, haematocrite value or platelet count apart from slight reduction in platelet count in between group A and B, while there is a steady decrease in red blood cell count [RBCs] and haemoglobin concentration [Hb] in the same group and in between the three groups. There was significant increase in prothrombin time, activated partial thromboplastin time and international normalized ratio [INR] in group A, while in groups E and C shows increase in prothrombin time and INK Prothrombin concentration was significantly decreased in the three groups. Fibrinogen concentration was significantly deceased in the same group and in between groups. Factor VIII concentration shows no significant difference in the same group and in between groups. Also, in AT III concentration shows slight reduction in it but no significant difference in the same group and in between groups. Fibrin degradation product [FDP] show no significant difference in the same group and in between groups, while the concentration of thrombin antithrombin complex [TAT] in our study shows significant increase in group A and C but in between groups there were no significant changes. The relationship between haemodilution thrombosis and haemostasis is probably more complicated than we used to believe. We found limited crystalloids administration with slow rate of infusion during surgery is beneficial for patient postoperative coagulation. Intravenous fluid administration, while being routine therapy for patients in operating rooms, may be harmful used in rapid fluid loading

Endothelial cell dysfunction and inflammatory process in type 1 diabetic patients with-and without micro vascular disease

Endothelial cell dysfunction results in altered production of cell adhesion molecules [CAMs] that may be involved in the pathogenesis of diabetic microvascular disease. Increased circulating cytokines may also be involved in this process. The aim of the present study was to evaluate levels of some CAMs and cytokines in children and adolescents with type 1 diabetes. It was also aimed to assess these parameters in relation to microvascular complications and certain risk factors. The study included 45 cases with type 1 diabetes aged 8-22 years of whom, 30 cases had evidence of microangiopathy [retinopathy or nephropathy] and 15 cases had not. Fifteen apparently healthy matchable subjects were included as controls. Cases were subjected to full history taking and physical examination. Direct ophthalmoscopy and fluorescein angiography were used to diagnose retinopathy, while nephropathy was diagnosed by detection of microalbuminuria. Level of glycated hemoglobin [HbA[1c]] and serum levels of sVCAM-1 and sE-selectin as well as IL-6 and TNF alpha were assessed for all patients and controls. The results showed that diabetic patients as a whole had significantly higher serum levels of sVCAM-lt sE-selectin, IL-6 and TNF alpha than controls. Post pubertal age, long duration of illness, obesity and high HbA[1c] level were significant risk factors for higher levels of CAMs. Significant positive correlations were found between levels of HbA[1c] and each of serum levels of sE-selectin and IL-6. Also significant positive correlations were found between each of serum levels of sVCAM-1 and sE-selectin, and IL-6 and TNF alpha. Patients with evidence of microangiopathy had significantly higher level of sVCAM-1 than cases without, and the latter group had significantly higher level of sE-selectin than controls. It is concluded that young patients with type 1 diabetes had significant markers of endothelial cell dysfunction particularly in those with microvascular disease. Screening of diabetic patients with E-selectin may help early diagnosis of endothelial dysfunction. Strict glycemic control and new therapeutic targets are mandatory to improve diabetic outcome in such cases

Coagulation defects and platelets function in splenectomized and non-splenectomized beta-thalassemic children

The aim of this work is to evaluate the coagulation defects and platelet function in beta-thalassemic children before and after splenectomy. Also to evaluate the effect of L-carnitine therapy on the coagulation events and platelet function in these patients. The study included 56 beta-thalassemic children who were admitted at the Hematology Unit in the Pediatric University Hospital - Assiut with 20 sex and age matched children as controls. They were subjected to clinical examination and laboratory investigations in the form of: screening tests for coagulation: PT, APTT TT, PC and fibrinogen, natural anticoagulants studies like protein S, protein C and antithrombin III activity and platelet response to adinosindiphosphate [ADP], ristocetin [Rist], collagen and arachidonic acid [AA]. Nineteen children did splenectomy and these studies were done after 2 months of this manover. L-Carnitine therapy in a dose of 3 gm orally daily for 2 months was given to 20 non-splenectomized beta-thalassernic children and the previous follow up laboratorial studies were done. It was found that platelet response to ADP, Rist, collagen and AA was significantly decreased in non-splenoctomized patients and significantly increased in the splenectomized ones in comparison to controls. The coagulation screen tests showed significant defect in the form of prolonged PT, APTT, TT and low PC with decrease fibrinogen levels in both splenectomized and nonsplenecloinized beta-thalassemic children in comparison to controls with no significant difference between before and after splenectomy. Natural anticoagulants except protein S were significantly lower in both non-splenectomized and splenectomized beta-thalassemic children than those of the controls with no difference between before and after splenectomy. L-Carnitine therapy improved the platelet aggregation in the non splenectomized beta-thalasseinic children with no affection on the coagulation tests and natural anticoagulants. In conclusion, thalassemia major can be complicated by defective platelet aggregation and bleeding tendency. Splenectomy causes increased platelet aggregation which with the decreased levels of natural anticoagulants lead to the liability to thromboembolic complications. L-Carnitine might affect and improve platelet aggregation in non-splenectomized children but it could aggravate the thromboembolic complications in the non-splenectomized ones. Iron overload prevention with iron celation and antioxidants is recommended to prevent platelet aggregation and coagulation defects. Salicylates therapy to cases with thromboembolic complications might decrease thrombus formation and dangerous events

Gene polymorphism of factor V and variceal bleeding in infants and children

The aim of this work is to evaluate the presence of factor V Leiden mutation and the activity of the natural anticoagulants in variceal bleeding in infants and children. This study included 50 infants and children with variceal bleeding who were admitted at the Gastroenterologoy, Hepatology and Malnutrition Unit, Pediatric University Hospital, Assiut University. The search was done in the period from January 2004 till July 2006. The age was between 5 months up to 14 years with mean age of 8.7 +/- 3.9 years. Twenty children of matchable age and sex were enrolled as controls. After the consent of the parents of patients and controls complete clinical examination with the following investigations for the cases and controls were done: 1. Liver function tests [total bilirubin, direct bilirubin, Alanine transaminase [ALT], Aspartate transaminase [AST], Alkaline phosphatase [ALP]] and hepatitis markers. 2. Prothrombin time [PT]. 3. Activated partial thromboplastine time [APTT]. 4. Thrombin time [TT]. 5. Prothrombin concentration [PC]. 6. Fibrinogen. 7. Natural anticoagulants; Protein S, Protein C, Antithrombin III [A TIII]. For cases the following investigations were done: 1. Evaluation of factor V Leiden mutation. 2. Abdominal ultrasound and Doppler. 3. Ultrasound guided needle biopsy to the liver and pathological examination. 4. Upper endoscopy with sclerotherapy or band ligation if needed. Follow up endoscopy after 2 months was done for each case. Out of the 50 patients 14 patients [28%] were diagnosed to have extrahepatic portal hypertension [EHPH] due to portal vein thrombosis [PVT]. 5 of them gave a history of admission in the neonatal intensive care unit and 7 suffered liver cirrhosis. The rest of cases 36[72%] were diagnosed as having intrahepatic portal hypertension [IHPH] 8/50 [16%] cryptogenic cirrhosis, 5/50 [10%] congenital hepatic fibrosis, 10/50 [20%] chronic HBV infection, 5/50 [10%] chronic HCV infection, 3/50 [6%] autoimmune hepatitis, 2/50 [4%] Wilson disease, 1/50 [2%] biliary cirrhosis and 2/50 [4%] neonatal hepatitis. Oesophageal varices was detected in 40 [80%], both oesophageal and gastric varices in 6 [12%] and isolated gastric in 4 [8%] of the cases. In cases with IHPH serum bilirubin and indirect bilirubin as well as liver transaminases and ALP were significantly higher than those of the EHPH and controls. No significant difference was found between EHPH and the controls. Natural anticoagulants were significantly decreased in cases with IHPH in comparison to EHPH and controls. Cases with EHPH show low levels of the natural anticoagulants in 4 while normal values were found in the remaining 10 patients. Leiden mutation was positive in 6 cases of portal vein thrombosis [42%] 4 of them suffered liver cirrhosis and in 3 cases with chronic HCV and in 2 cases with chronic HBV. One of the causes of portal hypertension in infants and children is portal vein thrombosis. PVT may be due to local precipitating factors as umbilical catheterization, umbilical sepsis or neonatal sepsis or due to an inherited factor like inherited thrombophilic mutation as FVL mutation that causes activated protein C resistance. Other inherited factors like inherited deficiency of Protein S, Protein C and ATIII may be the cause of PVT. Band ligation of the oesophageal varices may be beneficial in the treatment especially in cases due to PVT. Sclerotherapy may represent a trigger factor for PVT in cirrhotic patients with genetic thrombophilia. Screening for FVL mutation could be helpful in cases of hepatic cirrhosis to prevent PVT and also is diagnostic for most of the unexplained cases. The use of anticoagulant therapy maybe useful in the recently discovered cases of PVT and so decrease the risk to develop varices and their complications

Factors associated with gallstones in patients with chronic renal failure treated by haemodialysis in upper Egypt

Studies performed to date on the prevalence of gallstones in chronic renal failure [CRF] on haemodialysis [HD] have given contradictory results. to evaluate the frequency and percentage of gallstones and its main associated risk factors in a group of Egyptian haemodialysis patients. The study included 147 patients with CRF on HD randomly selected from Assiut and Sohag University renal dialysis units in Upper Egypt [102 males, 45 females]. The screening protocol included complete medical history, female parity, as well as, use of estrogen therapy by females. History of diabetes mellitus and duration of haemodialysis were also recorded. Body mass index [BMI] was calculated and a number of biochemical parameters [total cholesterol and triglycerides, serum calcium, phosphorus and uric acid] were estimated in fasting serum. An ultrasound scan of the gall bladder and biliary tract was performed with a 3.5 MHz linear probe after at least 12 h fasting. In addition, the prevalence of gallstones in the general population of the same geographical region was calculated after revising available data in ultrasonography reports. The mean age of CRF patients was 43 +/- 14.2 years and mean duration of dialysis was 30 +/- 30.5 months. Gallstones were diagnosed in 22.4% of HD patients and this was mildly significantly higher in women than men [31.1% in women vs 18.6% in men, P=0.05] and this percentage was significantly higher than that of the general population in the same geograbical region [1.6% of the total examined] [P=0.001]. The percentage of gallstones didnt increase significantly with increasing age or duration of dialysis. We noticed an insignificantly raised risk for gallstones with use of estrogen by females, diabetes mellitus and smoking in males [OR=3.2, 1.6, 1.2 respectively; P >0.05 for all of them]. No significant difference was noted between CRF patients with and without gallstones in the studied biochemical parameters except for mean serum calcium that was significantly higher in patients with gallstones [9.8 +/- 1.3 vs 8.1 +/- 1.1; P=0.04]. The percentage of gallstones in a group of Egyptian patients on HD is higher than that of the general population of the same area. Apart from female sex, the traditional risk factors associated with gallstones in the non-uraemic general population appear not to play a significant role in gallstone formation in HD patients. Estrogen use in females, presence of diabetes mellitus and smoking in males, have insignificantly raised the risk for gallstones in these patients. Changes in serum calcium appear to play a role. Our results suggest that other factors inherent to kidney pathology may contribute to this high percentage of gallstones in CRF patients on haemodialysis

Relation of leptin and proinflammatory cytokines to anorexia and wasting in pulmonary and extrapulmonary tuberculosis

Tuberculosis is the classic cause of "consumption," but the exact pathogenesis of such wasting is largely unknown. Animal studies in other conditions suggest that leptin may be a mediator between pro inflammatory cytokine activity and wasting. Because leptin is involved in weight regulation and cellular immunity, it may have a role in tuberculosis-associated wasting. Qims: 1] To estimate leptin concentration in a group of active pulmonary or extra pulmonary tuberculosis as compared to healthy control subjects. 2] To study the relationship between serum leptin, anorexia and wasting. 3] To study the correlation between serum leptin and proinflammatory cytokines [TNF-d, IL-1,IL-6] Patients and Non-diabetic Egyptian adults with pulmonary [n=26] and extrapulmonary tuberculosis [n=19] as well as 20 healthy controls were recruited into a case-control study. Body mass index [BMI], C- reactive protein, serum leptin, TNF-a, interleukin-1 and 6 were measured. According to the calculated BMI, eighteen patients were wasted [40%] and 27 [60%] were not wasted. Mean serum leptin was significantly lower in tuberculous patients than controls and in wasted than non-wasted patients. TNF-a, IL-l.IL-6 were significantly higher in patients than controls. Only IL-6 was significantly higher in wasted than non-wasted patients Serum leptin showed a significant positive correlation with BMI. While, IL-6 had a significant negative correlation with BMI Moreover, stepwise linear regression analyses showed that IL-6 was the only factor significantly contributing to loss of appetite [anorexia] in tuberculous patients. leptin does not appear to be part of the proinflammatory cytokine response in human tuberculosis. Changes in leptin are entirely appropriate for the changes in body mass index. Altered leptin activity cannot, therefore, be held responsible for the weight loss and anorexia so often associated with tuberculosis infection. Anorexia and wasting seem primarily determined by the level of inflammatory cytokine [IL-6]