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Mediastinal germ cell tumours are a rare group of extragonadal germ cell tumours with less than 5% prevalence of all germ cell tumours. Primary mediastinal germ cell tumours themselves account for 16-36% of the extragonadal germ cell tumours. Along the spectrum of osteosarcoma, parosteal osteosarcoma is a well- differentiated surface osteosarcoma with a prevalence of 4% of all osteosarcoma. As such synchronous primary parosteal osteosarcoma and primary mediastinal germ cell tumour are exceedingly rare. This leads to complexity in determining the most appropriate chemotherapy for two different types of tumours and its potential side effects of reduced immunity leading to potential secondary infection. Here we report a case of a 16-year-old boy who presented with synchronous primary osteosarcoma and primary mediastinal germ cell tumour, complicated with atypical mycobacterial infection post-operatively. Additionally, we discuss our choice of chemotherapy and the management of the atypical mycobacterial infection.

Therapeutic drug monitoring of pegylated L-asparaginase (ASNase) ensures the drug effectiveness in childhood acute lymphoblastic leukaemia (ALL) patients. The biological drug property with variable immunogenic host clearance, and the prescription of its generic formulation urge the need for a reliable assay to ensure an optimal treatment and improve outcome. This study aimed to optimise an existing isocratic reversed-phase high performance liquid chromatography (RP-HPLC) method with an automated pre-column sample derivatisation and injection program, and a computational algorithm for measuring serum pegylated ASNase activity in children with ALL. Nath et al.'s method in 2009 was adopted and modified using a pegylated ASNase. A set of Microsoft Excel macros was developed for the serum drug activity computation. An Agilent InfinityLab LC Series 1260 Infinity II Quaternary System with fluorescence detection was employed with an Agilent Poroshell 120 EC-C18 4.6×100 mm, 2.7 µm analytical column. System flow rate was optimised to 2.0 mL/min with 40×10 -6 /bar pump compressibility. The O-phthaldialdehyde (OPA) solution composition was optimised to 1 % o-phthaldialdehyde, 0.8 % 2-mercaptoethanol, 7.13 % methanol, and 1.81 % sodium tetraborate. The pre-column derivatisation program mixed 0.1 µL sample with 25 µL OPA solution before the automated injection. Method validation was according to the ICH guidelines. Total analysis time was 15 min, with L-aspartic acid eluted at 0.96 min and internal standard at 4.7 min. The calibration curves showed excellent linearity (R ≥0.9999). Interday precision for the drug activity at 0.1 IU/mL, 0.5 IU/mL, and 1 IU/mL were 4.15 %, 3.05 %, and 3.09 % (n = 6). Mean %error for the drug activity at 0.1 IU/mL, 0.5 IU/mL, and 1 IU/mL were 0.90±4.41 %, -1.37±3.04 %, and -3.03±3.02 % (n = 6). Limit of quantitation was 0.03 IU/mL. Majority of the patients' serum drug activity fell within the assay calibration range. Our improved method is automated, having shorter analysis time with a well-maintained separation resolution that enables a high-throughput analysis for application., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: C-Khai Loh reports financial support was provided by Malaysia Ministry of Higher Education. C-Khai Loh has patent Automated RP-HPLC with Microsoft Excel Macros for Serum Pegylated L-Asparaginase Activity Measurement and Calculation; File Number: UKM.IKB.800–4/1/5337 pending to Universiti Kebangsaan Malaysia. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Lymphatic malformation (LM) is a congenital lymphatic dysplasia associated with the p110α subunit of PI3K (PIK3CA) mutation. A two-year-old boy presented with a history of noisy breathing from the age of two months, which was progressively worsening. Inspiratory stridor was audible with subcostal recession. Flexible nasopharyngolaryngoscopy (FNPLS) revealed an enlarged right arytenoid. Other supraglottic structures were normal, and bilateral vocal cords were mobile. Direct laryngoscopy showed that the right arytenoid was enlarged with a smooth surface. On the subsequent visit, there was a painless soft lateral neck swelling, 4 cm x 4 cm in size, with normal skin. MRI confirmed LM with the predominantly macro-cystic component, involving primarily the right neck and upper mediastinum, causing airway compression. Sirolimus therapy was initiated, and at one month of follow-up after the treatment, his stridor had improved. The incidence of stridor secondary to head and neck tumors such as teratomas, hemangiomas, and LM accounts for less than 3%. The typical manifestation of LM often involves a painless, soft, and compressible mass that progressively increases in size. Features of macrocystic LM on MRI are multilocular and hyperintense cystic mass on T2-weighted imaging. The treatment methods for LM include surgical and non-surgical options. Despite being an off-label application, the response rate of sirolimus therapy in children with LM is reported to be 91%, and the first clinical response was observed in less than three weeks. Stridor is frequently encountered in children but rarely due to head and neck tumors. However, as in our case, a large LM may cause recurrent airway obstruction, and the neck swelling may appear later. Atypical airway findings, especially endoscopic examination, in a child with stridor should be complemented with imaging to examine the possibility of extra-laryngeal mass or external compression., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Venkatasamy et al.)

L-asparaginase is effective as part of the first line childhood acute lymphoblastic leukaemia (ALL) treatment regimen but suffers the risk of antibody production causing immune-mediated sequelae. This article aimed to describe the clinical implication of L-asparaginase hypersensitivity and review the types of antibodies and genetic polymorphisms contributing to it. Clinical or subclinical L-asparaginase hypersensitivity may lead to suboptimum therapeutic effect and jeopardise the clinical outcome in ALL children. Anti-asparaginase antibodies immunoglobulin (Ig)G, IgM and IgE were identified in the L-asparaginase hypersensitivities. Enzyme-linked immunosorbent assay (ELISA) is commonly used to quantify the IgG and IgM levels. The role of IgE in mediating L-asparaginase hypersensitivity is contradictory. Moreover, the presence of antibodies may not necessarily correlate inversely with the L-asparaginase efficacies in some studies. Patients with specific genetic variants have been shown to be more susceptible to clinical hypersensitivity of L-asparaginase. With the advance of technology, gene polymorphisms have been identified among Caucasians using whole-genome or exon sequencing, but the evidence is scanty among Asians. There is lack of pre-clinical study models that could help in understanding the pathophysiological pathway co-relating the gene expression and anti-asparaginase antibody formation. In conclusion, future research studies are required to fill the current gap in understanding the immune mediated reactions towards L-asparaginase upon its administration and its potential impact to the disease outcome., Competing Interests: Conflict of Interest None., (© Penerbit Universiti Sains Malaysia, 2023.)

Background: Non-transfusion-dependent β-thalassaemia (NTDβT) is a subset of inherited haemoglobin disorders characterised by reduced production of the β-globin chain of haemoglobin leading to anaemia of varying severity. Although blood transfusion is not a necessity for survival, it may be required to prevent complications of chronic anaemia, such as impaired growth and hypercoagulability. People with NTDβT also experience iron overload due to increased iron absorption from food sources which becomes more pronounced in those requiring blood transfusion. People with a higher foetal haemoglobin (HbF) level have been found to require fewer blood transfusions, thus leading to the emergence of treatments that could increase its level. HbF inducers stimulate HbF production without altering any gene structures. Evidence for the possible benefits and harms of these inducers is important for making an informed decision on their use., Objectives: To compare the effectiveness and safety of the following for reducing blood transfusion for people with NTDβT: 1. HbF inducers versus usual care or placebo; 2. single HbF inducer with another HbF inducer, and single dose with another dose; and 3. combination of HbF inducers versus usual care or placebo, or single HbF inducer., Search Methods: We used standard, extensive Cochrane search methods. The latest search date was 21 August 2022., Selection Criteria: We included randomised controlled trials (RCTs) or quasi-RCTs comparing single HbF inducer with placebo or usual care, with another single HbF inducer or with a combination of HbF inducers; or comparing different doses of the same HbF inducer., Data Collection and Analysis: We used standard Cochrane methods. Our primary outcomes were blood transfusion and haemoglobin levels. Our secondary outcomes were HbF levels, the long-term sequelae of NTDβT, quality of life and adverse events., Main Results: We included seven RCTs involving 291 people with NTDβT, aged two to 49 years, from five countries. We reported 10 comparisons using eight different HbF inducers (four pharmacological and four natural): three RCTs compared a single HbF inducer to placebo and seven to another HbF inducer. The duration of the intervention lasted from 56 days to six months. Most studies did not adequately report the randomisation procedures or whether and how blinding was achieved. HbF inducer against placebo or usual care Three HbF inducers, HQK-1001, Radix Astragali or a 3-in-1 combined natural preparation (CNP), were compared with a placebo. None of the comparisons reported the frequency of blood transfusion. We are uncertain whether Radix Astragali and CNP increase haemoglobin at three months (mean difference (MD) 1.33 g/dL, 95% confidence interval (CI) 0.54 to 2.11; 1 study, 2 interventions, 35 participants; very low-certainty evidence). We are uncertain whether Radix Astragali and CNP have any effect on HbF (MD 12%, 95% CI -0.74% to 24.75%; 1 study, 2 interventions, 35 participants; very low-certainty evidence). Only medians on haemoglobin and HbF levels were reported for HQK-1001. Adverse effects reported for HQK-1001 were nausea, vomiting, dizziness and suprapubic pain. There were no prespecified adverse effects for Radix Astragali and CNP. HbF inducer versus another HbF inducer Four studies compared a single inducer with another over three to six months. Comparisons included hydroxyurea versus resveratrol, hydroxyurea versus thalidomide, hydroxyurea versus decitabine and Radix Astragali versus CNP. No study reported our prespecified outcomes on blood transfusion. Haemoglobin and HbF were reported for the comparison Radix Astragali versus CNP, but we are uncertain whether there were any differences (1 study, 24 participants; low-certainty evidence). Different doses of the same HbF inducer Two studies compared two different types of HbF inducers at different doses over two to six months. Comparisons included hydroxyurea 20 mg/kg/day versus 10 mg/kg/day and HQK-1001 10 mg/kg/day, 20 mg/kg/day, 30 mg/kg/day and 40 mg/kg/day. Blood transfusion, as prespecified, was not reported. In one study (61 participants) we are uncertain whether the lower levels of both haemoglobin and HbF at 24 weeks were due to the higher dose of hydroxyurea (haemoglobin: MD -2.39 g/dL, 95% CI -2.80 to -1.98; very low-certainty evidence; HbF: MD -10.20%, 95% CI -16.28% to -4.12%; very low-certainty evidence). The study of the four different doses of HQK-1001 did not report results for either haemoglobin or HbF. We are not certain if major adverse effects may be more common with higher hydroxyurea doses (neutropenia: risk ratio (RR) 9.93, 95% CI 1.34 to 73.97; thrombocytopenia: RR 3.68, 95% CI 1.12 to 12.07; very low-certainty evidence). Taking HQK-1001 20 mg/kg/day may result in the fewest adverse effects. A combination of HbF inducers versus a single HbF inducer Two studies compared three combinations of two inducers with a single inducer over six months: hydroxyurea plus resveratrol versus resveratrol or hydroxyurea alone, and hydroxyurea plus l-carnitine versus hydroxyurea alone. Blood transfusion was not reported. Hydroxyurea plus resveratrol may reduce haemoglobin compared with either resveratrol or hydroxyurea alone (MD -0.74 g/dL, 95% CI -1.45 to -0.03; 1 study, 54 participants; low-certainty evidence). We are not certain whether the gastrointestinal disturbances, headache and malaise more commonly reported with hydroxyurea plus resveratrol than resveratrol alone were due to the interventions. We are uncertain whether hydroxyurea plus l-carnitine compared with hydroxyurea alone may increase mean haemoglobin, and reduce pulmonary hypertension (1 study, 60 participants; very low-certainty evidence). Adverse events were reported but not in the intervention group. None of the comparisons reported the outcome of HbF., Authors' Conclusions: We are uncertain whether any of the eight HbF inducers in this review have a beneficial effect on people with NTDβT. For each of these HbF inducers, we found only one or at the most two small studies. There is no information on whether any of these HbF inducers have an effect on our primary outcome, blood transfusion. For the second primary outcome, haemoglobin, there may be small differences between intervention groups, but these may not be clinically meaningful and are of low- to very low-certainty evidence. Data on adverse effects and optimal doses are limited. Five studies are awaiting classification, but none are ongoing., (Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Objective: Patients with thalassemia major do require lifetime blood transfusions that eventually result in iron accumulation in different organs. We described the usefulness of using magnetic resonance imaging (MRI) T2 * imaging values for the evaluation of pancreatic iron load in these patients, and we correlated it with MRI T2 * haemosiderosis of the myocardium and liver that has been recognized as a non-invasive assessment of iron overload among patients with thalassemia major., Materials and Methods: We conducted a cross-sectional study on 39 patients with thalassemia major in one of the tertiary university hospitals for a 1-year period. Demographic data were collected from the patient's history. MRI T2 * of the pancreas, liver, and heart were executed on all patients in the same setting. Objective values of iron overload in these organs were obtained using the MRI post-processing software from online software., Results: A total of 32 (82.1%) patients had pancreatic iron overload including 2 patients (5.1%) with severe iron overload and 15 patients (38.5%) with moderate and mild iron overload, respectively. Nine patients (23.1%) had myocardial iron overload, which included 3 patients (7.7%) who had severe cardiac haemosiderosis. Notably, 37 patients (94.9%) had liver iron overload, which included 15 patients (38.5%) who had severe liver haemosiderosis. There was a moderate positive correlation between the relaxation time of the pancreas and heart haemosiderosis (r = 0.504, P < 0.001). No significant correlation was found between the relaxation time of the pancreas with the liver and the heart with the liver., Conclusion: Pancreatic haemosiderosis precedes cardiac haemosiderosis, which establishes a basis for initiating earlier iron chelation therapy to patients with thalassemia major., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Hoe, Git, Loh, Abdul Latiff, Hong, Abdul Hamid, Wan Sulaiman and Mohd Zaki.)

The Siriraj I G γ( A γδβ) 0 -thalassaemia is a novel mutation involving a 118kb deletion of the β-globin gene cluster. It was first reported in 2012 in two unrelated families from the southern part of Thailand. The carriers in the heterozygous state are clinically asymptomatic. Nonetheless, its complex interaction with other β-thalassaemia could give rise to different clinical phenotypes, ranging from mild thalassaemia intermedia to thalassaemia major. We report here a case of a six-year-old Malay boy, presented with pallor, growth failure and hepatosplenomegaly. His haemoglobin at presentation was 9.2g/dL with a mean cell haemoglobin of 22.6pg and a mean cell volume of 69.9fl. His peripheral blood smear showed features of thalassaemia intermedia. Haemoglobin (Hb) analysis revealed markedly raised Hb F (83%), normal HbA2 levels and absent HbA. Deoxyribonucleic acid (DNA) analysis showed compound heterozygous IVS1-1 (G→T) β-globin gene mutation and Siriraj I G γ( A γδβ) 0 -deletion (genotype β IVS1-1 / β Siriraj I deletion ). Both his father and elder sister are carriers of Siriraj I G γ( A γδβ) 0 -thalassaemia while his mother carries IVS1-1 (G→T) gene mutation. Clinically, the patient is transfusion dependent on six weekly regime. To the best of our knowledge, this is the first reported case in Malaysia involving unique Siriraj I G γ( A γδβ) 0 -thalassaemia and IVS1-1 (G→T) in a compound heterozygous state. In summary, detection of Siriraj I G γ( A γδβ) 0 -thalassaemia is essential as this deletion can lead to severe disease upon interaction with a β-thalassemia point mutation as demonstrated in our case. The establishment of effective carrier screening and genetic counselling is important to prevent its adverse consequences.

Introduction: Yolk sac tumour (YST) or endodermal sinus tumour is rare and typically seen in gonads., Case Report: We described a case of extragonadal vaginal YST in a one year and seven months old girl who presented with vaginal discharge and bleeding, and discuss its differential diagnosis and potential pitfalls in immunohistochemistry. She was found to have a suprapubic mass on examination. The serum alpha fetoprotein was 11919.4 ng/mL. Computed tomography of the pelvis revealed a large 6.4 cm heterogenous pelvic mass. Colposcopic examination of the pelvis showed a fungating vaginal mass that was subsequently confirmed as a yolk sac tumour. Immunohistochemically, the malignant cells were positive toward CKAE1/AE3, AFP and glypican-3, as well as CD117., Discussion: Solid pattern extragonadal vaginal YST may morphologically resemble dysgerminoma that is also CD117 positive, while the glandular pattern YST may have clear cytoplasm and is positive for cytokeratin; hence, may resemble clear cell carcinoma. Being mindful of these potential diagnostic caveats is necessary to prevent misdiagnosis.

Objectives: The objective of this study is to describe the imaging features of medulloblastoma (MB) and correlate the MR characteristics with the different histological subtype of MB with 2-year survival., Materials and Methods: This is a retrospective descriptive study. A total of 29 patients diagnosed with MB from January 2005 to December 2015 were included in this study. The MRI brain and spine studies of these patients were retrieved and reviewed by a pediatric radiologist and a neuroradiologist independently, both blinded from the histological type of the MB. The HPE slides were also retrieved and reviewed by a pathologist., Results: 80% of desmoplastic MB showed the presence of intracranial leptomeningeal seeding and 57.1% of anaplastic MB showed the presence of necrosis. The presence of intracranial leptomeningeal seeding ( P = 0.002) and necrosis ( P = 0.019) was predictive of the histological subtypes. There is a significant correlation between the enhancement pattern and the 2-year outcome ( P = 0.03) with 6 out of 8 patients whose tumors showed minimal enhancement having disease progression within 2 years. A significant correlation was also seen between the presence of necrosis with a poorer outcome ( P = 0.03) and between the HPE subtype and 2-year outcome ( P = 0.03) with anaplastic MB having the poorest prognosis., Conclusion: MR imaging features of intracranial leptomeningeal seeding and the presence of necrosis were correlated with a specific histologic subtype of MB. The enhancement pattern as well as necrosis correlated with 2-year poorer outcome of the disease., Competing Interests: There are no conflicts of interest., (Copyright: © 2020 Indian Journal of Radiology and Imaging.)

Introduction: A smooth transition of healthcare for young people with chronic illnesses from paediatric to adult healthcare services is important to ensure optimal outcome. At the moment, there are no standard guidelines to assess a patient's readiness to transfer care., Methods: A cross-sectional study using a self-administered questionnaire, adapted from UNC (University of North Carolina) TRxANSITION self-assessment tool was conducted to evaluate patients' transition care readiness in paediatric haematology and paediatric diabetes clinic., Results: A total of 80 patients (37 thalassaemia and 43 diabetes) with the mean age of 21.2 (SD±4.3) years, were recruited during the 3-month study period. Majority of the patients have basic knowledge regarding their medications, and were able to comply with their follow-up. The mean total score obtained by the respondents on this questionnaire was 15.3 (SD±3.59). Self-management skills and knowledge on disease were the two poorly scored section; with mean score of 3.78 (SD±1.38) and 4.28 (SD±1.20) respectively. Overall, only 21 (26.2%) respondents obtained high score (score above 75th percentile). Seventy-five percent of the respondents admitted that they were not ready for transfer to an adult healthcare service yet at the time of the study., Conclusion: We suggest that patients with high score should be prepared for transition to adult facility whereas those with a low score need to be identified to ensure provision of continuous education.

Background: Acquired thrombotic thrombocytopenia purpura is very rarely encountered in children. It is often misdiagnosed initially when the condition is not inherited., Case Presentation: We describe a 3-year-old Malay boy who presented with simple febrile seizure and had no neurological deficit, however, he was found to have microangiopathic hemolytic anemia, thrombocytopenia, and elevated serum lactate dehydrogenase. An ADAMTS13 assay results showed zero activities (0%), and markedly high level of ADAMTS13 inhibitor (93.15 U/mL) confirming the diagnosis of secondary thrombotic thrombocytopenia purpura. He received fresh frozen plasma infusions for 3 days and subsequently his platelet levels normalized. Serial ADAMTS13 assay results showed improvement. He was also given a short course of prednisolone after which the ADAMTS13 activity normalized (> 114%) at the end of prednisolone course., Conclusions: At presentation, acquired thrombotic thrombocytopenia purpura in a very young child is commonly misdiagnosed as other conditions like idiopathic thrombocytopenic purpura, Evans syndrome, atypical hemolytic-uremic syndrome, or malignancy. ADAMTS13 assay should be performed early when thrombotic thrombocytopenia purpura is suspected as this condition is associated with dire consequences.

Giant cell tumor (GCT) is one of the most common tumors of bone and is the most common precursor of aneurysmal bone cysts (ABC). The clinical behavior of concurrent GCT and ABC can be very aggressive in children. GCT of the ribs, with or without ABC, is rarely seen in children. We report a case of an 8-year-old girl with GCT and associated ABC of the ribs who presented with sudden onset of chest pain and breathlessness due to a hemothorax. The patient was successfully treated by surgical resections and arterial embolization. She has remained well for 4 years after the initial surgery.

A four-year-old Ibanese boy presented with subacute abdominal distension for two months duration. Ultrasound and computed tomography (CT) scan showed solid liver masses as well as bowel and intraperitoneal lesions. Initial diagnosis of intraperitoneal inflammatory process as in tuberculosis with non-liquefied liver abscess with differential diagnosis of neoplastic process was made. Liver biopsy and peritoneal fluid analysis revealed Burkitt's lymphoma (BL). We aim to highlight the diagnostic challenge of BL in this young age group emphasizing on the ultrasound and CT features of intraabdominal BL. We would also want to stress the importance of early diagnosis of BL as it is known to be the most aggressive tumour within 24 hours yet to have good survival if early diagnosis was made.

Background: Non-transfusion dependent beta thalassaemia is a subset of inherited haemoglobin disorders characterised by reduced production of the beta globin chain of the haemoglobin molecule leading to anaemia of varying severity. Although blood transfusion is not a necessity for survival, it is required when episodes of chronic anaemia occur. This chronic anaemia can impair growth and affect quality of life. People with non-transfusion dependent beta thalassaemia suffer from iron overload due to their body's increased capability of absorbing iron from food sources. Iron overload becomes more pronounced in those requiring blood transfusion. People with a higher foetal haemoglobin level have been found to require fewer blood transfusions. Hydroxyurea has been used to increase foetal haemoglobin level; however, its efficacy in reducing transfusion, chronic anaemia complications and its safety need to be established., Objectives: To assess the effectiveness, safety and appropriate dose regimen of hydroxyurea in people with non-transfusion dependent beta thalassaemia (haemoglobin E combined with beta thalassaemia and beta thalassaemia intermedia)., Search Methods: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register, compiled from electronic database searches and handsearching of relevant journals. We also searched ongoing trials registries and the reference lists of relevant articles and reviews.Date of last search: 30 April 2016., Selection Criteria: Randomised or quasi-randomised controlled trials of hydroxyurea in people with non-transfusion dependent beta thalassaemia comparing hydroxyurea with placebo or standard treatment or comparing different doses of hydroxyurea., Data Collection and Analysis: Two authors independently applied the inclusion criteria in order to select trials for inclusion. Both authors assessed the risk of bias of trials and extracted the data. A third author verified these assessments., Main Results: No trials comparing hydroxyurea with placebo or standard care were found. However, we included one randomised controlled trial (n = 61) comparing 20 mg/kg/day with 10 mg/kg/day of hydroxyurea for 24 weeks.Both haemoglobin and foetal haemoglobin levels were lower at 24 weeks in the 20 mg group compared with the 10 mg group, mean difference -2.39 (95% confidence interval - 2.8 to -1.98) and mean difference -1.5 (95% confidence interval -1.83 to -1.17), respectively. Major adverse effects were significantly more common in the 20 mg group, for neutropenia risk ratio 9.93 (95% confidence interval 1.34 to 73.97) and for thrombocytopenia risk ratio 3.68 (95% confidence interval 1.13 to 12.07). No difference was reported for minor adverse effects (gastrointestinal disturbances and raised liver enzymes). The effect of hydroxyurea on transfusion frequency was not reported.The overall quality for the outcomes reported was graded as very low mainly because the outcomes were derived from only one small study with an unclear method of allocation concealment., Authors' Conclusions: There is no evidence from randomised controlled trials to show whether hydroxyurea has any effect compared with controls on the need for blood transfusion. Administration of 10 mg/kg/day compared to 20 mg/kg/day of hydroxyurea resulted in higher haemoglobin levels and seems safer with fewer adverse effects. It has not been reported whether hydroxyurea is capable of reducing the need for blood transfusion. Large well-designed randomised controlled trials with sufficient duration of follow up are recommended.

Haemoglobin (Hb) Lepore is a variant Hb consisting of two α-globin and two δβ-globin chains. In a heterozygote, it is associated with clinical findings of thalassaemia minor, but interactions with other haemoglobinopathies can lead to various clinical phenotypes and pose diagnostic challenges. We reported a pair of siblings from a Malay family, who presented with pallor and hepatosplenomegaly at the ages of 21 months and 14 months old. The red cell indices and peripheral blood smears of both patients showed features of thalassaemia intermedia. Other laboratory investigations of the patients showed conflicting results. However, laboratory investigation results of the parents had led to a presumptive diagnosis of compound heterozygote Hb Lepore/β-thalassaemia and co-inheritance α+-thalassaemia (-α3.7). Hb Lepore has rarely been detected in Southeast Asian countries, particularly in Malaysia. These two cases highlight the importance of family studies for accurate diagnosis, hence appropriate clinical management and genetic counseling.

Benchtop nuclear magnetic resonance (NMR) pulsed field gradient (PFG) and relaxation measurements were used to monitor the clathrate hydrate shell growth occurring in water droplets dispersed in a continuous cyclopentane phase. These techniques allowed the growth of hydrate inside the opaque exterior shell to be monitored and, hence, information about the evolution of the shell's morphology to be deduced. NMR relaxation measurements were primarily used to monitor the hydrate shell growth kinetics, while PFG NMR diffusion experiments were used to determine the nominal droplet size distribution (DSD) of the unconverted water inside the shell core. A comparison of mean droplet sizes obtained directly via PFG NMR and independently deduced from relaxation measurements showed that the assumption of the shell model-a perfect spherical core of unconverted water-for these hydrate droplet systems is correct, but only after approximately 24 h of shell growth. Initially, hydrate growth is faster and heat-transfer-limited, leading to porous shells with surface areas larger than that of spheres with equivalent volumes. Subsequently, the hydrate growth rate becomes mass-transfer-limited, and the shells become thicker, spherical, and less porous.

Objectives: To determine the behavioural impact of chemotherapy in survivors of acute lymphoblastic leukaemia (ALL) treated with chemotherapy only and to identify treatment-related or sociodemography-related factors that might be associated with behavioural outcome., Methods: We examined 57 survivors of childhood ALL, who were off treatment for at least 2 years and were in remission, aged 4-18 years, and 221 unrelated healthy controls. The Child Behaviour Checklist (CBCL) parent report was used either in English or in Bahasa Malaysia (the national language of Malaysia) to assess the behavioural outcome., Results: Childhood ALL survivors had significantly higher scores on externalising behaviour on the CBCL parent report than did controls. Higher problem scores were found in ALL survivors with single parents on 'total problems' (P = 0.03) and subscales 'withdrawn' (P = 0.03), 'social problems' (P < 0.01) and 'delinquent behaviour' (P = 0.03) than in survivors with married parents. Significant associations were seen between a lower education level of the father and the variables representing internalising (withdrawn, anxious/depressed) and externalising (aggressive behaviour). We observed trends on higher scores in all scales in ALL survivors with single parents than in controls with single parents or with fathers with low education level, especially primary education only., Conclusions: Malaysian childhood ALL survivors had a significantly increased risk for externalising behavioural problems, and there was a trend towards increased risk of problems in many other behavioural scales. Understanding the sociocultural dimension of patients' health is important to be able to design the most appropriate remedy for problem behaviours detected in this multi-ethnic population., (© 2014 John Wiley & Sons Ltd.)

Hb Adana [HBA2: c179G>A (or HBA1); p.Gly60Asp] is a rare hemoglobin (Hb) variant due to a mutation at codon 59 of the α2- or α1-globin gene resulting in a glycine to aspartic acid substitution. Two siblings with a unique coinheritance of Hb Adana and Hb Constant Spring (Hb CS, α142, Term→Gln, TAA>CAA; HBA2: c.427 T>C) (α(codon 59)α/α(CS)α), were compared phenotypically with another two siblings carrying the Hb Adana mutation and a 3.7 kb deletion (α(codon 59)α/-α(3.7)). Although they all had α-thalassemia intermedia (α-TI), the former were clinically more severe than the latter. The first pair of siblings presented at a much younger age than the second pair and showed lower Hb levels and significant extramedullay hemopoiesis. Another case of a hydropic fetus as a result of Hb H/Hb Adana is also described. Their clinical phenotypes and hematological parameters are all presented for comparison.

Aim: To identify differentially expressed hydrophobic proteins in colorectal cancer., Methods: Eighteen pairs of colorectal cancerous tissues in addition to tissues from normal mucosa were analysed. Hydrophobic proteins were extracted from the tissues, separated using 2-D gel electrophoresis and analysed using Liquid Chromatography Tandem Mass Spectrometry (LC/MS/MS). Statistical analysis of the proteins was carried out in order to determine the significance of each protein to colorectal cancer (CRC) and also their relation to CRC stages, grades and patients' gender., Results: Thirteen differentially expressed proteins which were expressed abundantly in either cancerous or normal tissues were identified. A number of these proteins were found to relate strongly with a particular stage or grade of CRC. In addition, the association of these proteins with patient gender also appeared to be significant., Conclusion: Stomatin-like protein 2 was found to be a promising biomarker for CRC, especially in female patients. The differentially expressed proteins identified were associated with CRC and may act as drug target candidates.

We report the case of a patient with intrathoracic extramedullary hematopoiesis presenting as a posterior mediastinal tumor in response to chronic hemolytic anemia. Noninvasive studies including chest roentgenograms, computed tomographic scans, magnetic resonance images, and nuclear scans can establish the diagnosis in most cases. In equivocal cases, transthoracic needle biopsy and open biopsy should be considered. Surgical resection is recommended only for patients with symptoms of compression.

Extraperitoneal, perivesical pelvic effusions may be hemorrhagic or uriniferous, the latter resulting from extraperitoneal rupture of the bladder or disruption of the posterior urethra. The effusions may be recognized on anteroposterior radiographs of the pelvis by (a) displacement of the bladder (small effusion); (b) obliteration of the normal soft-tissue anatomy within the pelvis (moderate effusion); and (c) upward displacement of the pelvic ileal loops and extension of the effusion into the flank stripes (large effusion). Perivesical effusions most frequently accompany anterior pelvic arch injuries, i.e., double vertical and Malgaigne fractures and fractures involving, or separation of, the pubic symphysis.

Insertion of a hooked stylet into the region of a mammographic abnormality is a simple method of localization prior to biopsy. The hook on the stylet does not permit movement of the localization device away from the lesion during the interval between placement and surgical excision. A xeroradiograph of the biopsy specimen determines whether the suspected region was obtained surgically.

Effects of diphenylhydantoin (DPH) on amphibian atrial myocardium K were investigated using a method which permits both total tissue K and tension response to be monitored continuously. In normal (nondigitalized) preparations, DPH caused a decrease in average K efflux, a net gain of tissue K, and negativeinotropy at low perfusate K concentrations. However, the DPH-induced gain of tissue K was abolished at high perfusate K concentrations while marked negative inotropy was still observed. It is concluded that a gain of tissue K is not the cause of DPH-induced negative inotropy. When digitalis-induced inotropy was associated with tissue K loss, DPH reversed tissue K loss and positive inotropy and caused a decrease in average K efflux. In the presence of toxic effects of digitalis, DPH reversed the K loss and the contracture, but the loss of developed tension was not reversed by DPH. Transmembrane resting potentials and action potential duration were reduced by digitalis and were returned to or above control levels in the presence of DPH. The present findings are consistent with the hypothesis that the therapeutic effect of DPH in digitalis toxicity is brought about by an inhibition of K efflux. This would tend to minimize the loss of tissue K which results from sodium pump inhibition.