Keep the corners; impact of chemotherapy on renal function

Implication for health policy/practice/research/medical education: Due to kidneys’ role in metabolism and excretion of toxic waste, they are subjects to drug toxicity. keywords: Cancer, Chemotherapy, Malignant tumor, Reactive oxygen species, Renal toxicity, Tubulointerstitial injur

The impact of N-myc amplification on median survival in children with neuroblastoma

Background: Neuroblastoma is the most common extracranial malignant solid tumor in children under 5 years, and it is characterized by wide clinical and biological heterogeneity. N-myc oncogene amplification is considered to be one of the most important prognostic factors used to evaluate survival in these patients. Objectives: The aim of our study was to determine amplification of the N-myc oncogene using real-time quantitative polymerase chain reaction (PCR) and to show the influence of N-myc amplified tumors on the overall survival rate. Patients and Methods: This study is an analytical historical cohort study of forty children with neuroblastoma admitted to the Shafa Hospital, Iran from 1999 to 2010. Paraffined blocks of tumoral tissue were analyzed for N-myc amplification by a PCR. The degree of N-myc amplification was derived from the ratio of the N-myc oncogene and the single copy reference gene, NAGK. In the statistical analysis, a Kaplan-Meier survival analysis was used. Results: We found a variable degree of N-myc amplification, from 3 to 2 200, in 32 of the 40 neuroblastomas (80%). NMYC amplification was seen more frequently in patients older than 2.5 years (71.9%), stage 4 (65.6%) and female (53.1%). Median survival time in the males was significantly longer than in the females (P = 0.03). The overall median survival for N-myc amplified tumor patients was 20 months, and 30 months for the non amplified tumors. Conclusions: The N-myc amplified tumors may increase the probability of more aggressive behavior and rapid tumor progression, especially in advanced stages of neuroblastoma. This study confirmed the importance of obtaining correct measurements of oncogene amplification in the early evaluation of neuroblastomas in order to target more aggressive therapies in patients with a higher risk of cancer progression

Von Willebrand factor propeptide and pathophysiological mechanisms in European and Iranian patients with type 3 von Willebrand disease enrolled in the 3WINTERS-IPS study

Background Type 3 von Willebrand disease (VWD) is a severe bleeding disorder caused by the virtually complete absence of von Willebrand factor (VWF). Pathophysiological mechanisms of VWD like defective synthesis, secretion, and clearance of VWF have previously been evaluated using ratios of VWF propeptide (VWFpp) over VWF antigen (VWF:Ag) and factor (F)VIII coagulant activity (FVIII:C) over VWF:Ag. Objective To investigate whether the VWFpp/VWF:Ag and FVIII:C/VWF:Ag ratios may also be applied to understand the pathophysiological mechanism underlying type 3 VWD and whether VWFpp is associated with bleeding severity. Methods European and Iranian type 3 patients were enrolled in the 3WINTERS-IPS study. Plasma samples and buffy coats were collected and a bleeding assessment tool was administered at enrolment. VWF:Ag, VWFpp, FVIII:C, and genetic analyses were performed centrally, to confirm patients' diagnoses. VWFpp/VWF:Ag and FVIII:C/VWF:Ag ratios were compared among different variant classes using the Mann-Whitney test. Median differences with 95% confidence intervals (CI) were estimated using the Hodges-Lehmann method. VWFpp association with bleeding symptoms was assessed using Spearman's rank correlation. Results Homozygosity/compound heterozygosity for missense variants showed higher VWFpp level and VWFpp/VWF:Ag ratio than homozygosity/compound heterozygosity for null variants ([VWFpp median difference, 1.4 IU/dl; 95% CI, 0.2-2.7; P = .016]; [VWFpp/VWF:Ag median difference, 1.4; 95% CI, 0-4.2; P = .054]). FVIII:C/VWF:Ag ratio was similarly increased in both. VWFpp level did not correlate with the bleeding symptoms (r = .024; P = .778). Conclusions An increased VWFpp/VWF:Ag ratio is indicative of missense variants, whereas FVIII:C/VWF:Ag ratio does not discriminate missense from null alleles. The VWFpp level was not associated with the severity of bleeding phenotype.Peer reviewe

Bleeding symptoms in patients diagnosed as type 3 von Willebrand disease : Results from 3WINTERS-IPS, an international and collaborative cross-sectional study

Background Type 3 von Willebrand's disease (VWD) patients present markedly reduced levels of von Willebrand factor and factor VIII. Because of its rarity, the bleeding phenotype of type 3 VWD is poorly described, as compared to type 1 VWD. Aims To evaluate the frequency and the severity of bleeding symptoms across age and sex groups in type 3 patients and to compare these with those observed in type 1 VWD patients to investigate any possible clustering of bleeding symptoms within type 3 patients. Methods We compared the bleeding phenotype and computed the bleeding score (BS) using the MCMDM-1VWD bleeding questionnaire in patients enrolled in the 3WINTERS-IPS and MCMDM-1VWD studies. Results In 223 unrelated type 3 VWD patients, both the BS and the number of clinically relevant bleeding symptoms were increased in type 3 as compared to type 1 VWD patients (15 versus 6 and 5 versus 3). Intracranial bleeding, oral cavity, hemarthroses, and deep hematomas were at least five-fold over-represented in type 3 VWD. A more severe bleeding phenotype was evident in patients having von Willebrand factor antigen levels <20 IU/dL at diagnosis in the two merged cohorts. In type 3 patients, there was an apparent clustering of hemarthrosis with gastrointestinal bleeding and epistaxis, whereas bleeding after surgery or tooth extraction clusters with oral bleeding and menorrhagia. Conclusions In the largest cohort of type 3 VWD patients, we were able to describe a distinct clinical phenotype that is associated with the presence of a more severe hemostatic defect.Peer reviewe

Better differential diagnosis of iron deficiency anemia from beta-thalassemia trait

Objective: Iron deficiency anemia (IDA) and beta-thalassemia trait (ß-TT) are the most common forms of microcytic anemia. This study was conducted to compare the validity of various discrimination indices in differentiating β-TT from IDA by calculating their sensitivity, specificity and Youden's index.Methods: Totally 323 subjects (173 children and 150 adults) with microcytic anemia were involved in this study. We calculated 10 discrimination indices in all patients with IDA and β-TT. We divided the patients into two different groups as younger or older than 10 years. Results: None of the indices showed sensitivity and specificity of 100% in the patients older than 10 years, and in the patients younger than 10 years, only Shine & Lal index showed sensitivity close to 90% and specificity of 100%. The most accurate discriminative index for patients younger than 10 years was Shine & Lal and for those older than 10 years it was RDW index. According to Youden's index, Shine & Lal and RBC count showed the greatest diagnostic value in patients younger than 10 years and RDW and RBC count indices in those older than 10 years. Conclusion: None of the indices was completely sensitive and specific in differentiation between β-TT and IDA. Mean and median mean cell Hb density (MCHD) were very close to normal values in both IDA and β-TT patients, but in the case of mean density of Hb/liter (MDHL), we found that the mean and median were significantly higher than normal values in β-TT and lower than normal values in IDA patients. In our study, Youden's index of RBC and Shine & Lal were the highest and most reliable indices in differentiating β-TT from IDA in the patients younger than 10 years. For patients older than 10 years, the most reliable discrimination indices were RBC and RDW

Effects of Nutritional variables in children with iron deficiency anemia

Introduction: Iron deficiency (ID) is the most prevalent nutritional disorder in the world. The prevalence of iron deficiency anemia (IDA) is about 9% in toddlers, 9-11% in adolescent girls and less than 1% in teenage boys. IDA presents when there is not sufficient iron for haemoglobin synthesis. In particular it has negative effects on the behavior, cognitive performance, immune system and physical growth of infants, preschool and school age children. Material and Methods: Blood samples of 337 randomly selected children (6-59 months) living in the Ahwaz, Khuzestan province, were taken. Serum ferritin, Complete Blood Cell (CBC) and hematological indices were measured Results and Discussion: In this study 61.1% of the children had serum ferritin less than 12mcg/dl. Prevalence of IDA were 29.1 %. The results showed that most children with IDA were at 12-23 months. Families with more than 6 children had 4.49 times greater chance of IDA. The mean of breast-feeding in non-IDA children was higher than IDA children (17.6 and 16.3 months respectively, P>0.05). In this study families who gave tea to their children for 1-11 months had the highest prevalence of IDA. Conclusion: There are several main risk factors for ID & IDA in the children. Parent's illiteracy, family income and using cow's milk before 12 months are among most important risk factors for iron deficiency for children

Spontaneous iliopsoas muscle hematoma in a patient with von Willebrand disease: a case report

Abstract Introduction Iliopsoas hemorrhage is a serious complication of bleeding disorders that occurs most commonly in patients with hemophilia and less commonly in patients with von Willebrand disease. It causes severe pain, muscle dysfunction and occasionally femoral nerve palsy. We describe the case of a patient with von Willebrand disease type 3 with a large iliopsoas hematoma who was treated with a von Willebrand factor concentrate (Humate-P). Case presentation A 20-year-old Iranian man was referred to our emergency ward because of the gradual onset of right flank pain. He was known to have been diagnosed with von Willebrand disease type 3 at age two years old. Magnetic resonance imaging showed a mass in the right iliopsoas muscle. The diagnosis of iliopsoas hemorrhage and partial femoral nerve palsy was established, and he responded to medical treatment. Conclusion We report a case of von Willebrand disease type 3 with spontaneous iliopsoas hematoma associated with femoral nerve palsy that was well managed with Humate-P treatment.</p

Side Effects of Hydroxyurea in Patients with Major and Intermediat B-Thalassemia

Introduction: Patients referred to as having thalassemia major are usually those who come to medical attention in the first year of life and subsequently require regular transfusions to survive. Those who present later or who seldom need transfusions are said to have thalassemia intermediaHydroxyurea, an s-phase-specific and non-DNA-hypomethylating chemotherapeutic agents is capable of inducing HbF synthesis.Patients & Methods: The study evaluated hydroxyurea complications in a cohort of 28 patients with major (n=20) and intermediate thalassemia (n=8). HU was started in a dose of 10 mg/kg daily and then increased by 5 mg/kg daily every 4-6 weeks until toxicity occurred or clinical response was achieved.Results: We reviewed the records of 28 patients with intermediate and major b-thalassemia. The statistical analysis did not show a significant correlation between age at diagnosis, age of starting HU, duration of HU treatment, dose of HU and ethnicity.Side effects of HU have been recorded in 21 (75%) patients.Adverse effects were hair loss (n=8; 28.57%), hyper pigmentation (n=4; 14.28%), nausea and vomiting (n=2; 7.14%), abdominal pain (n=4; 14.28%), and increase in hepatic enzymes (n=2; 7.14%).Neurologic complications were headache (n=7; 25%), vertigo (n=1; 3.57%) and drowsiness (n=1; 3.57%).Conclusion: According to the results of this and other studies, it seems that HU therapy in thalassemic patients can be safely used but can be started at low doses and increased slowly , monitoring the patient's respons

Adrenal extramedullary hematopoiesis associated with β-thalassemia major

The presence of apparently normal hematopoietic tissue outside of bone marrow cavity is defined as extramedullary hema - topoiesis (EMH). EMH is a rare complication in thalassemia major (TM) and adrenal gland as well. This report describes a case of adrenal EMH in a 26-year-old man with β-TM. He has been transfused with regular blood transfusion since 9 months. During the routine physical examination he was incidentally found to have a hypoechoic mass at his abdominal ultrasonography. Abdominal computed tomography scan revealed a right well-defined suprarenal mass 7.7¥7.3¥5.8 cm in size. The diagnosis of EMH was confirmed with ultrasonographic-guided fine needle biopsy. Treatment options which include intensified regular blood transfusion and hydroxyurea have been started