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Sample records for acute childhood myositis

  1. Chest wall myositis in a patient with acute coronary syndrome.

    Science.gov (United States)

    Hussein, Laila; Al-Rawi, Harith

    2014-10-13

    We describe a case of a 42-year-old man who presented to the emergency department with severe left-sided chest pain and chest tenderness of 1-day duration. The pain was episodic and was aggravated by any chest wall movement. His initial blood tests and ECG were suggestive of acute coronary syndrome (ACS). However, his pattern of pain, lack of response to opiates, raised creatine kinase and signs of pleurisy on chest radiograph raised a suspicion of an alternative diagnosis. The patient showed a dramatic response in pain relief to non-steroidal anti-inflammatory medication. He was suspected to have chest wall myositis with pleural involvement in the form of pleurodynia. His serology test was positive for coxsackie virus antibodies. We will discuss in this case report the pathognomonic features, diagnosis and treatment of a rare infectious condition known as Bornholm disease. 2014 BMJ Publishing Group Ltd.

  2. Acute myositis associated with concurrent infection of rotavirus and norovirus in a 2-year-old girl

    Directory of Open Access Journals (Sweden)

    Kei Yamamoto

    2015-09-01

    Full Text Available Rotavirus and norovirus are common pathogens associated with gastroenteritis in children. Although rotavirus occasionally induces central nervous system disease, only 3 cases with rotavirus-induced acute myositis have been reported in the English literature. We recently treated a female patient with acute myositis associated with gastroenteritis induced by concurrent infection with rotavirus and norovirus. Having suffered from gastroenteritis for 3 days, she suddenly developed myositis affecting her lower extremities with concomitant creatine kinase elevation. Herein, we present our patient and review the previous cases including those reported in the Japanese literature.

  3. Rheumatoid myositis leading to acute lower extremity compartment syndrome: a case-based review.

    Science.gov (United States)

    Jo, Daniel; Pompa, Tiffany; Khalil, Ambreen; Kong, Frank; Wetz, Robert; Goldstein, Mark

    2015-10-01

    Muscle pain and weakness in a rheumatoid arthritis (RA) patient has a broad differential, and myositis should be considered early in the disease course as serious limb and life-threatening sequelae may occur. A 55-year-old woman with a past medical history of methotrexate-controlled RA presented with right leg pain for 4 days. The patient suffered sensory loss in the right foot and decreased strength in the toes. Lab tests revealed elevated creatine kinase, ESR, and anti-rheumatoid factor antibody titers. CT scan revealed myositis of posterior compartment muscles. Progressive edema, pain, and neuromuscular deficits persisted despite steroid and antibiotic therapy, so the patient was taken for urgent fasciotomy for acute compartment syndrome. The muscle biopsy showed diffuse mononuclear cell infiltration as well as perivascular and perineural involvement consistent with rheumatoid myositis (RM). The patient did well post-op on a prednisone taper. This case underlines the systemic nature of RA and exemplifies the severity of inflammation that may lead to grave consequences such as compartment syndrome. The histopathology is diagnostic when there is evidence of mononuclear cell infiltration; however, this is not entirely specific. Early, aggressive therapy with immunosuppressives is warranted in such patients. RM has not, to our knowledge, been recorded to cause acute compartment syndrome. Clinicians should be aware of this uncommon manifestation of RA keeping the various presentations of rheumatoid disease in mind when faced with these patients.

  4. Chest wall myositis in a patient with acute coronary syndrome

    OpenAIRE

    Hussein, Laila; Al-Rawi, Harith

    2014-01-01

    We describe a case of a 42-year-old man who presented to the emergency department with severe left-sided chest pain and chest tenderness of 1-day duration. The pain was episodic and was aggravated by any chest wall movement. His initial blood tests and ECG were suggestive of acute coronary syndrome (ACS). However, his pattern of pain, lack of response to opiates, raised creatine kinase and signs of pleurisy on chest radiograph raised a suspicion of an alternative diagnosis. The patient showed...

  5. Clinical and laboratory description of a series of cases of acute viral myositis

    Directory of Open Access Journals (Sweden)

    Silvana Paula Cardin

    2015-10-01

    Full Text Available ABSTRACT OBJECTIVE: Describe the clinical and laboratory profile, follow-up, and outcome of a series of cases of acute viral myositis. METHOD: A retrospective analysis of suspected cases under observation in the emergency department was performed, including outpatient follow-up with the recording of respiratory infection and musculoskeletal symptoms, measurement of muscle enzymes, creatine phosphokinase (CPK, lactate dehydrogenase (LDH, transaminases (AST and ALT, blood count, C-reactive protein, and erythrocyte sedimentation rate in the acute phase and during follow-up until normalization. RESULTS: Between 2000 and 2009, 42 suspected cases were identified and 35 (27 boys were included. The median age was 7 years and the diagnosis was reported in 89% in the first emergency visit. The observed respiratory symptoms were cough (31%, rhinorrhea (23%, and fever (63%, with a mean duration of 4.3 days. Musculoskeletal symptoms were localized pain in the calves (80%, limited ambulation (57%, gait abnormality (40%, and muscle weakness in the lower limbs (71%, with a mean duration of 3.6 days. There was significant increase in CPK enzymes (5507 ± 9180 U/L, LDH (827 ± 598 U/L, and AST (199 ± 245 U/L, with a tendency to leukopenia (4590 ± 1420 leukocytes/mm3. The complete recovery of laboratory parameters was observed in 30 days (median, and laboratory and clinical recurrence was documented in one case after 10 months. CONCLUSION: Typical symptoms with increased muscle enzymes after diagnosis of influenza and self-limited course of the disease were the clues to the diagnosis. The increase in muscle enzymes indicate transient myotropic activity related to seasonal influenza, which should be considered, regardless of the viral identification, possibly associated with influenza virus or other respiratory viruses.

  6. Clinical and laboratory description of a series of cases of acute viral myositis.

    Science.gov (United States)

    Cardin, Silvana Paula; Martin, Joelma Gonçalves; Saad-Magalhães, Claudia

    2015-01-01

    Describe the clinical and laboratory profile, follow-up, and outcome of a series of cases of acute viral myositis. A retrospective analysis of suspected cases under observation in the emergency department was performed, including outpatient follow-up with the recording of respiratory infection and musculoskeletal symptoms, measurement of muscle enzymes, creatine phosphokinase (CPK), lactate dehydrogenase (LDH), transaminases (AST and ALT), blood count, C-reactive protein, and erythrocyte sedimentation rate in the acute phase and during follow-up until normalization. Between 2000 and 2009, 42 suspected cases were identified and 35 (27 boys) were included. The median age was 7 years and the diagnosis was reported in 89% in the first emergency visit. The observed respiratory symptoms were cough (31%), rhinorrhea (23%), and fever (63%), with a mean duration of 4.3 days. Musculoskeletal symptoms were localized pain in the calves (80%), limited ambulation (57%), gait abnormality (40%), and muscle weakness in the lower limbs (71%), with a mean duration of 3.6 days. There was significant increase in CPK enzymes (5507±9180U/L), LDH (827±598U/L), and AST (199±245U/L), with a tendency to leukopenia (4590±1420) leukocytes/mm(3). The complete recovery of laboratory parameters was observed in 30 days (median), and laboratory and clinical recurrence was documented in one case after 10 months. Typical symptoms with increased muscle enzymes after diagnosis of influenza and self-limited course of the disease were the clues to the diagnosis. The increase in muscle enzymes indicate transient myotropic activity related to seasonal influenza, which should be considered, regardless of the viral identification, possibly associated with influenza virus or other respiratory viruses. Copyright © 2015 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

  7. Bacterial, fungal, parasitic, and viral myositis.

    Science.gov (United States)

    Crum-Cianflone, Nancy F

    2008-07-01

    Infectious myositis may be caused by a broad range of bacterial, fungal, parasitic, and viral agents. Infectious myositis is overall uncommon given the relative resistance of the musculature to infection. For example, inciting events, including trauma, surgery, or the presence of foreign bodies or devitalized tissue, are often present in cases of bacterial myositis. Bacterial causes are categorized by clinical presentation, anatomic location, and causative organisms into the categories of pyomyositis, psoas abscess, Staphylococcus aureus myositis, group A streptococcal necrotizing myositis, group B streptococcal myositis, clostridial gas gangrene, and nonclostridial myositis. Fungal myositis is rare and usually occurs among immunocompromised hosts. Parasitic myositis is most commonly a result of trichinosis or cystericercosis, but other protozoa or helminths may be involved. A parasitic cause of myositis is suggested by the travel history and presence of eosinophilia. Viruses may cause diffuse muscle involvement with clinical manifestations, such as benign acute myositis (most commonly due to influenza virus), pleurodynia (coxsackievirus B), acute rhabdomyolysis, or an immune-mediated polymyositis. The diagnosis of myositis is suggested by the clinical picture and radiologic imaging, and the etiologic agent is confirmed by microbiologic or serologic testing. Therapy is based on the clinical presentation and the underlying pathogen.

  8. Acute hemiplegia in childhood

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    Okuno, Takehiko; Takao, Tatsuo; Itoh, Masatoshi; Konishi, Yukuo; Nakano, Shozo (Kyoto Univ. (Japan). Faculty of Medicine)

    1983-04-01

    The results of CT in 100 patients with acute hemiplegia in childhood are reported here. The etiology was various: 2 patients had infratentorial brain tumors, 56 had cerebral vascular diseases, 3 had head injuries, 16 had intracranial infectious diseases, one had postinfectious encephalomyelitis, one had multiple sclerosis, 2 had epilepsy, and the diagnosis of 19 were unknown. Eleven patients had a normal CT and a good prognosis. As for the type of onset, there were patients of type 1 with fever and 42 with convulsions and unconsciousness; those of type 2 with convulsions and unconsciousness were 12, and those of type 3 without fever and convulsions were 46. This classification is assumed to be useful, as the type of onset is characteristic of the etiology. Six patients were diagnosed correctly by repeated examinations, although the first CT did not reveal any remarkable findings. Capsular infarction, occlusion of the posterior cerebral artery in acute hemiplegia in childhood, abnormal findings of the internal capsule, thalamus, and midbrain in a patient with postinfectious encephalomyelitis, and a diffuse low density in the CT of the unilateral hemisphere in the patients with acute encephalopathy and acute hemiplegia of an obscure origin have been found after the introduction of computerized tomography.

  9. Childhood Acute Lymphoblastic Leukemia

    DEFF Research Database (Denmark)

    Pui, Ching-Hon; Yang, Jun J; Hunger, Stephen P

    2015-01-01

    PURPOSE: To review the impact of collaborative studies on advances in the biology and treatment of acute lymphoblastic leukemia (ALL) in children and adolescents. METHODS: A review of English literature on childhood ALL focusing on collaborative studies was performed. The resulting article...... determinants of drug resistance and toxicities have been identified to help develop targeted therapy. Several genetic polymorphisms have been recognized that show susceptibility to developing ALL and that help explain the racial/ethnic differences in the incidence of ALL. CONCLUSION: The information gained...

  10. [Acute orbital myositis and idiopathic inflammatory pseudotumor in children: three cases].

    Science.gov (United States)

    Grouteau, E; Chaix, Y; Armbruster, V; Lesueur, L; Sevely, A; Rubie, H; Carrière, J P

    1998-02-01

    Orbital pseudo-tumors account for approximately 8% of the orbital tumors. They are scarcely described in children and raise diagnostic dilemas, especially when they present as an isolated extra-ocular muscle swelling called idiopathic orbital myositis (IOM). A diagnosis of inflammatory orbital pseudotumors (IOPT) was made in three children aged 7, 13 and 14 years from clinical and CT scan and/or MRI findings associated with histological data in two of them. Two of these IOPT presented as IOM. Analysis was made in a effort to eliminate intra-orbital tumors, especially rhabdomyosarcoma. The abrupt onset of the orbital signs, often related in the literature, was not a specific diagnostic criterion regarding to embryonic rhabdomyosarcoma. The inconstant presence of inflammatory signs and the absence of local osseous defect could be more discriminating. Although diagnostic procedure, including histological documentation, was difficult, even dangerous, surgical biopsy should be recommended. Eventually, considering the mandatory multidisciplinary care, steroid therapy response should be evaluated as a diagnostic test.

  11. Acute severe childhood asthma

    African Journals Online (AJOL)

    and children must know exactly what to do when an acute attack occurs, and when to seek medical attention. This is very important if the child is using a home nebuliser as many parents continue to administer dose after dose of bronchodilator medication that does not provide oxygen. Failure to improve after a single dose of ...

  12. Risk Groups for Childhood Acute Lymphoblastic Leukemia

    Science.gov (United States)

    ... for cancer and certain genetic conditions affect the risk of having childhood ALL. Anything that increases your ... marrow or in other parts of the body. Risk Groups for Childhood Acute Lymphoblastic Leukemia Key Points ...

  13. Acute leukemia in early childhood

    Directory of Open Access Journals (Sweden)

    M. Emerenciano

    2007-06-01

    Full Text Available Acute leukemia in early childhood is biologically and clinically distinct. The particular characteristics of this malignancy diagnosed during the first months of life have provided remarkable insights into the etiology of the disease. The pro-B, CD10 negative immunophenotype is typically found in infant acute leukemia, and the most common genetic alterations are the rearrangements of the MLL gene. In addition, the TEL/AML1 fusion gene is most frequently found in children older than 24 months. A molecular study on a Brazilian cohort (age range 0-23 months has detected TEL/AML1+ve (N = 9, E2A/PBX1+ve (N = 4, PML/RARA+ve (N = 4, and AML1/ETO+ve (N = 2 cases. Undoubtedly, the great majority of genetic events occurring in these patients arise prenatally. The environmental exposure to damaging agents that give rise to genetic changes prenatally may be accurately determined in infants since the window of exposure is limited and known. Several studies have shown maternal exposures that may give rise to leukemogenic changes. The Brazilian Collaborative Study Group of Infant Acute Leukemia has found that mothers exposed to dipyrone, pesticides and hormones had an increased chance to give birth to babies with infant acute leukemia [OR = 1.48 (95%CI = 1.05-2.07, OR = 2.27 (95%CI = 1.56-3.31 and OR = 9.08 (95%CI = 2.95-27.96], respectively. This review aims to summarize recent clues that have facilitated the elucidation of the biology of early childhood leukemias, with emphasis on infant acute leukemia in the Brazilian population.

  14. Oral dexamethasone pulse therapy versus daily prednisolone in sub-acute onset myositis, a randomised clinical trial

    NARCIS (Netherlands)

    Van de Vlekkert, J.; Hoogendijk, J. E.; de Haan, R. J.; Algra, A.; van der Tweel, I.; van der Pol, W. L.; Uijtendaal, E. V.; de Visser, M.

    2010-01-01

    To determine if high-dose pulsed dexamethasone is more effective and safer than daily high-dose prednisolone in treatment-naive adult patients with inflammatory myopathies (sporadic inclusion body myositis excluded) we performed a multicenter, double-blind randomised controlled clinical trial with

  15. Global characteristics of childhood acute promyelocytic leukemia.

    Science.gov (United States)

    Zhang, L; Samad, A; Pombo-de-Oliveira, M S; Scelo, G; Smith, M T; Feusner, J; Wiemels, J L; Metayer, C

    2015-03-01

    Acute promyelocytic leukemia (APL) comprises approximately 5-10% of childhood acute myeloid leukemia (AML) cases in the US. While variation in this percentage among other populations was noted previously, global patterns of childhood APL have not been thoroughly characterized. In this comprehensive review of childhood APL, we examined its geographic pattern and the potential contribution of environmental factors to observed variation. In 142 studies (spanning >60 countries) identified, variation was apparent-de novo APL represented from 2% (Switzerland) to >50% (Nicaragua) of childhood AML in different geographic regions. Because a limited number of previous studies addressed specific environmental exposures that potentially underlie childhood APL development, we gathered 28 childhood cases of therapy-related APL, which exemplified associations between prior exposures to chemotherapeutic drugs/radiation and APL diagnosis. Future population-based studies examining childhood APL patterns and the potential association with specific environmental exposures and other risk factors are needed. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. Childhood acute lymphoblastic leukaemia and birthweight

    DEFF Research Database (Denmark)

    Roman, Eve; Lightfoot, Tracy; Smith, Alexandra G

    2013-01-01

    BACKGROUND: Heavy birthweight is one of the few established risk factors for childhood acute lymphoblastic leukaemia (ALL). To provide new insight into this relationship, particularly at the extremes (<1500 and > 4500 g), we pooled data from three of the largest childhood cancer case-control stud......BACKGROUND: Heavy birthweight is one of the few established risk factors for childhood acute lymphoblastic leukaemia (ALL). To provide new insight into this relationship, particularly at the extremes ( 4500 g), we pooled data from three of the largest childhood cancer case......-control studies ever conducted. METHODS: Birthweight and gestational age on 4075 children with ALL and 12,065 controls were collected during the course of three studies conducted in the USA, the UK and Germany in the 1990s. Information was obtained from mothers at interview, and the impact of bias was evaluated...

  17. Acute Myeloid Leukemia in Childhood

    OpenAIRE

    Yöntem, Ahmet; Bayram, İbrahim

    2018-01-01

    Acute leukemia is basically divided intoacute lymphoblastic leukemia and acute myeloid leukemia. About 15-20% ofchildhood leukemia is caused by acute myeloid leukemia.AML is classified according to morphological, cytochemical and immunophenotypiccharacteristics. AML patients may present with various clinical signsand symptoms due to leukemic cell infiltration. Age, gender, race, structuralfeatures of the patient and cytogenetic abnormalities are important factorsaffecting prognosis in AML. Th...

  18. Inclusion-Body Myositis: Diagnosis

    Science.gov (United States)

    ... MDA Blog Donate Search MDA.org Close Inclusion-Body Myositis (IBM) Share print email share facebook twitter ... with other muscle diseases, a doctor diagnoses inclusion-body myositis (IBM) by considering the individual’s personal history, ...

  19. Unusual presentations of childhood acute lymphoblastic leukaemia ...

    African Journals Online (AJOL)

    Childhood acute lymphoblastic leukaemia, (ALL) is increasingly reported to present in an atypical fashion which may have significant implications for treatment outcomes and survival. This case report presents a Nigerian child who's clinical and radiological features together with effusion cytological findings were suggestive ...

  20. Acute acquired comitant esotropia of childhood

    DEFF Research Database (Denmark)

    Hesgaard, Helena; Vinding, Troels

    2015-01-01

    PURPOSE: To identify characteristics of pediatric patients who develop acute acquired comitant esotropia (AACE) with and without intracranial disease. METHODS: We reviewed the charts of 48 children consecutively referred to the hospital with AACE during a 13-year period. Inclusion criteria were a...... of literature, we identified seven cause-specific types of AACE. Intracranial disease was present in 6%, and four risk factors were identified to guide clinicians when to perform brain imaging. Findings suggest AACE of childhood to be differentiated from AACE of adulthood.......: In all, 48 cases were recorded. The mean age at onset was 4.7 years, being significantly higher among children with intracranial disease. Seven cause-specific types of AACE in childhood were identified: The acute accommodative (n = 15, 31%), decompensated monofixation syndrome or esophoria (n = 13, 27...

  1. Acute Retinal Necrosis in Childhood

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    Yoav Y. Pikkel

    2014-05-01

    Full Text Available Background: Acute retinal necrosis (ARN is a viral syndrome consisting of uveitis/vitritis, occlusive vasculitis and peripheral necrosis. Few incidents are reported in children. The etiology is reactivated herpes simplex virus (HSV or varicella-zoster virus (VZV. Treatment with acyclovir is often used. The administration of oral glucocorticosteroids is of unproven benefit. Prognosis is variable but poor. Methods: Three weeks after contracting mild chickenpox, a healthy 4-year-old girl developed blurred vision in her right eye. Severely reduced visual acuity was noted, together with anterior uveitis, ‘mutton-fat' precipitates and vitral flare. Retinal vasculitis with necrosis was present. Serology for toxoplasma, cytomegalovirus and HIV was negative, while HSV and VZV IgG antibodies were positive. She was treated with 30 mg/kg of intravenous methylprednisolone (3 days, 30 mg of oral prednisone (3 days, and tapering for 8 weeks. Intravenous acyclovir was given for 10 days, followed by oral acyclovir for 4 months. Aspirin (100 mg/day was given for 4 months. Results: At 12 months, the girl felt good. Her right eye acuity was 6/9, with an intraocular pressure of 17 mm Hg. The peripheral retina showed scarring but no detachment. Conclusions: This is the first report of a once-daily high-dose methylprednisolone pulse therapy in one of the youngest known ARN cases. Pulsed steroid therapy was based on its known effectiveness in vasculitis, which is the main pathophysiology in ARN. There was no evidence of steroid-related viral over-replication. Our case achieved an excellent clinical and ophthalmic recovery in spite of the poor prognosis. The positive result of this case report provides a basis for further evaluation of high-dose steroid pulse therapy in ARN.

  2. [Acute disseminated encephalomyelitis in childhood].

    Science.gov (United States)

    Liptai, Zoltán; Ujhelyi, Eniko; Mihály, Ilona; Rudas, Gábor; Barsi, Péter

    2009-07-30

    Acute disseminated encephalomyelitis is a rare inflammatory demyelinating disorder often preceded by infection or vaccination. The purpose of the study was the systematic analysis of clinical, radiological and microbiological profiles of children treated at Szent László Hospital, and the comparison of findings with literature data. Demographic, infectological, clinical, radiological, laboratory and virological data of patients treated and followed-up between 1-Jan-1998 and 30-June-2008 were reviewed and analysed. 19 children met diagnostic criteria. Their mean age was 6.8 years. A prodromal illness--mostly febrile viral infection, upper respiratory infection or chickenpox--preceded neurological symptoms in 17 patients. All had polysymptomatic encephalopathy, 2 children had spinal symptoms. The cerebrospinal fluid was abnormal in all but one. A viral etiology was definite in 7 and probable in 8 cases. MRI disclosed white matter changes in 18, cortical and deep gray matter in 16, cerebellar in 6, brain stem in 14 and spinal cord changes in 2 cases. Repeat MRI performed mean 4 months later showed complete resolution in 6 and partial resolution in 11 patients. 13 patients received high-dose methylprednisolone, 2 of whom were also treated with plasma exchange and 1 with immunoglobulin. 9 children required mechanical ventilation. 2 patients died, 10 recovered without and 7 with sequelae. 2 patients developed further demyelinating events: multiple sclerosis and multiphasic disseminated encephalomyelitis, respectively. Clinical, radiological and follow-up results were similar to those published in literature however, triggering viruses were identified in a larger proportion of cases.

  3. Pure White Cell Aplasia and Necrotizing Myositis

    Directory of Open Access Journals (Sweden)

    Peter Geon Kim

    2016-01-01

    Full Text Available Pure white cell aplasia (PWCA is a rare hematologic disorder characterized by the absence of neutrophil lineages in the bone marrow with intact megakaryopoiesis and erythropoiesis. PWCA has been associated with autoimmune, drug-induced, and viral exposures. Here, we report a case of a 74-year-old female who presented with severe proximal weakness without pain and was found to have PWCA with nonspecific inflammatory necrotizing myositis and acute liver injury on biopsies. These findings were associated with a recent course of azithromycin and her daily use of a statin. Myositis improved on prednisone but PWCA persisted. With intravenous immunoglobulin and granulocyte-colony stimulating factor therapies, her symptoms and neutrophil counts improved and were sustained for months.

  4. Myositis ossificans: the mimicker

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    Govindarajan, Arunkumar; Sarawagi, Radha; Prakash, Manikka Lakshmanan

    2013-01-01

    A 14-year-old boy presented with upper backache and a painful swelling in the right paraspinal region for 7 days. He had no history of trauma. MRI showed a non-specific ill-defined heterogeneous lesion, which showed intense postcontrast enhancement. Ultrasonogram showed a peripheral sheet of calcification around the lesion. A CT scan showed a faint rim of calcification, which increased in thickness over weeks, confirming the diagnosis as myositis ossificans. We present our approach to the case and also review the imaging features of different stages of the disease process and their differentials. PMID:24326436

  5. Current Management of Childhood Acute Myeloid Leukemia.

    Science.gov (United States)

    Rubnitz, Jeffrey E

    2017-02-01

    The outcome for children with acute myeloid leukemia (AML) has improved significantly over the past 30 years, with complete remission and overall survival rates exceeding 90 and 60%, respectively, in recent clinical trials. However, these improvements have not been achieved by the introduction of new agents. Instead, intensification of standard chemotherapy, more precise risk classification, improvements in supportive care, and the use of minimal residual disease to monitor response to therapy have all contributed to this success. Nevertheless, novel therapies are needed, as the cure rates for many subtypes of childhood AML remain unacceptably low. Here, we briefly review advances in our understanding of the biology and genetics of AML, the results of recent clinical trials, and current recommendations for the treatment of children with AML.

  6. The EuroMyositis registry

    DEFF Research Database (Denmark)

    Lilleker, James B; Vencovsky, Jiri; Wang, Guochun

    2018-01-01

    AIMS: The EuroMyositis Registry facilitates collaboration across the idiopathic inflammatory myopathy (IIM) research community. This inaugural report examines pooled Registry data. METHODS: Cross-sectional analysis of IIM cases from 11 countries was performed. Associations between clinical subtyp...

  7. INCLUSION BODY MYOSITIS

    Directory of Open Access Journals (Sweden)

    Luh Yeni Laksmini

    2014-09-01

    Full Text Available Inclusion body myositis (IBM merupakan penyakit inflamasi pada otot yang bersifat progresif dengan penyebab yang tidak diketahui dan tidak menunjukkan respon yang baik terhadap berbagai terapi. Gambaran histopatologi IBM ditandai dengan infiltrat sel-sel limfosit diantara ruangan endomisial, di dalam otot dan di sekitar otot dengan fokus-fokus inklusi di dalam miosit (rimmed vacuole serta beberapa serat otot terlihat atrofi dan nekrosis. Dilaporkan wanita, usia 46 tahun dengan IBM. Keluhan utama pasien berupa kelemahan pada kedua tangan, kaki kanan terasa berat jika diangkat sehingga susah berjalan. Pemeriksaan saraf sensorik ekstremitas dekstra dan sinistra dalam batas normal. Pemeriksaan enzim cretinine kinase meningkat secara dramatik. Pemeriksaan histopatologi dari biospi otot gastrocnemius menunjukkan gambaran yang sesuai untuk IBM dan telah dilakukan penanganan dengan pemberian oral methilprednisolon 3x32 mg dan mecobalmin 1x500ìg intravena, namun tidak menunjukkan respon yang baik terhadap terapi dan akhirnya pasien meninggal. [MEDICINA 2013;44:118-123].

  8. Childhood Acute Lymphoblastic Leukemia: Progress Through Collaboration

    Science.gov (United States)

    Yang, Jun J.; Hunger, Stephen P.; Pieters, Rob; Schrappe, Martin; Biondi, Andrea; Vora, Ajay; Baruchel, André; Silverman, Lewis B.; Schmiegelow, Kjeld; Escherich, Gabriele; Horibe, Keizo; Benoit, Yves C.M.; Izraeli, Shai; Yeoh, Allen Eng Juh; Liang, Der-Cherng; Downing, James R.; Evans, William E.; Relling, Mary V.; Mullighan, Charles G.

    2015-01-01

    Purpose To review the impact of collaborative studies on advances in the biology and treatment of acute lymphoblastic leukemia (ALL) in children and adolescents. Methods A review of English literature on childhood ALL focusing on collaborative studies was performed. The resulting article was reviewed and revised by the committee chairs of the major ALL study groups. Results With long-term survival rates for ALL approaching 90% and the advent of high-resolution genome-wide analyses, several international study groups or consortia were established to conduct collaborative research to further improve outcome. As a result, treatment strategies have been improved for several subtypes of ALL, such as infant, MLL-rearranged, Philadelphia chromosome–positive, and Philadelphia chromosome–like ALL. Many recurrent genetic abnormalities that respond to tyrosine kinase inhibitors and multiple genetic determinants of drug resistance and toxicities have been identified to help develop targeted therapy. Several genetic polymorphisms have been recognized that show susceptibility to developing ALL and that help explain the racial/ethnic differences in the incidence of ALL. Conclusion The information gained from collaborative studies has helped decipher the heterogeneity of ALL to help improve personalized treatment, which will further advance the current high cure rate and the quality of life for children and adolescents with ALL. PMID:26304874

  9. Childhood vaccinations and risk of acute lymphoblastic leukaemia in children

    DEFF Research Database (Denmark)

    Søegaard, Signe Holst; Rostgaard, Klaus; Schmiegelow, Kjeld

    2017-01-01

    Background: It has been proposed that childhood vaccinations protect against acute lymphoblastic leukaemia (ALL) in children by modulation of future responses to common infections in childhood. However, the available studies provide inconsistent findings, and population-based cohort studies...... with longitudinal information on vaccinations are lacking.Methods: In a register-based cohort of all children born in Denmark from 1 January 1990 to 31 December 2008, followed up until age 15 years or 31 December 2009 (n=1 225 404), we evaluated exposure to childhood vaccination and risk of childhood ALL, including...... information on ALL subtypes. Using Cox regression, we estimated hazard ratios (HRs) comparing vaccinated with unvaccinated children.Results: Childhood ALL was diagnosed in 490 children during 10 829 194 person-years of follow-up. Neither the total number of vaccine doses received nor exposure to each...

  10. Myositis ossificans within the intercondylar notch treated arthroscopically

    Energy Technology Data Exchange (ETDEWEB)

    Leung, Allen H.; Desai, Panna [Hospital for Joint Diseases/New York University, Department of Pathology, New York, NY (United States); Rybak, Leon D. [Hospital for Joint Diseases/New York University, Department of Radiology, New York, NY (United States); Rose, Donald J. [Hospital for Joint Diseases/New York University, Department of Orthopedic Surgery, New York, NY (United States)

    2010-09-15

    We present a case of intraarticular myositis ossificans in the right knee of a child. Myositis ossificans (MO), though relatively rare in childhood and even more uncommon within a joint, should be included in the differential diagnosis of an intra-articular mass when indicated by the typical clinical, radiographic, and histologic findings. An 11-year-old male presented with a history of trauma to his right knee. Four weeks after the initial injury, an MRI demonstrated evidence of an ACL rupture with a ''cystic mass'' within the intercondylar notch along the anterior surface of the torn ligament. At subsequent arthroscopy, the mass noted on MRI was removed. The histology was consistent with MO. The authors believe this to be the first case of MO in the intercondylar notch detected by MRI, treated by arthroscopy, and confirmed by histology. (orig.)

  11. Myositis specific autoantibodies: changing insights in pathophysiology and clinical associations.

    NARCIS (Netherlands)

    Hengstman, G.J.D.; Engelen, B.G.M. van; Venrooij, W.J.W. van

    2004-01-01

    PURPOSE OF REVIEW: Defined autoantibodies are found in about half of the patients with myositis. Traditionally, these autoantibodies have been divided into myositis specific autoantibodies (MSAs) and myositis associated autoantibodies. Several studies have shown that MSAs are associated with

  12. Pharmacogenetics Influence Treatment Efficacy in Childhood Acute Lymphoblastic Leukemia

    DEFF Research Database (Denmark)

    Devidsen, M.L.; Dalhoff, K.; Schmiegelow, K.

    2008-01-01

    in treatment resistance and toxic side effects. As most childhood acute lymphoblastic leukemia treatment protocols include up to 13 different chemotherapeutic agents, the impact of individual SNPs has been difficult to evaluate. So far Focus has mainly been on the widely used glucocorticosteroids, methotrexate...

  13. Asparaginase-associated pancreatitis in childhood acute lymphoblastic leukaemia

    DEFF Research Database (Denmark)

    Wolthers, Benjamin O.; Frandsen, Thomas L.; Baruchel, André

    2017-01-01

    BACKGROUND: Survival for childhood acute lymphoblastic leukaemia surpasses 90% with contemporary therapy; however, patients remain burdened by the severe toxic effects of treatment, including asparaginase-associated pancreatitis. To investigate the risk of complications and risk of re-exposing pa...

  14. Etiology of common childhood acute lymphoblastic leukemia: the adrenal hypothesis

    DEFF Research Database (Denmark)

    Schmiegelow, K.; Vestergaard, T.; Nielsen, S.M.

    2008-01-01

    The pattern of infections in the first years of life modulates our immune system, and a low incidence of infections has been linked to an increased risk of common childhood acute lymphoblastic leukemia (ALL). We here present a new interpretation of these observations--the adrenal hypothesis...

  15. Childhood Acute Bacterial Meningitis in Benin City, Nigeria | Ojide ...

    African Journals Online (AJOL)

    Childhood acute bacterial meningitis (ABM) is a leading cause of morbidity and mortality in Nigeria. The usual practice of commencing antibiotic therapy before the complete laboratory result is available necessitates the knowledge of the current most frequent aetiologic agents of meningitis and the antibiogram in the local ...

  16. Acute Non-Traumatic Abdominal Pain in Childhood at Kenyatta ...

    African Journals Online (AJOL)

    2010-07-14

    Jul 14, 2010 ... The assessment and diagnosis of acute abdominal pain in childhood is clinically challenging. The epidemiologic correlates differ for different paediatric age groups and settings. Objectives ... Of non surgical causes, upper respiratory tract infections. (21%), gastroenteritis (15.6%) and non-specific abdominal ...

  17. Osteogenic toxicity in childhood acute lymphoblastic leukemia

    NARCIS (Netherlands)

    M.L. te Winkel (Mariël Lizet)

    2013-01-01

    textabstractBone mineral density (BMD) Our multi-center study in children treated according to the Dutch Childhood Oncology Group (DCOG)-ALL9 protocol showed a three-years cumulative incidence of fractures of 18%. BMD of ALL patients was lower than of healthy peers. The year after treatment

  18. Bacterial, Fungal, Parasitic, and Viral Myositis

    OpenAIRE

    Crum-Cianflone, Nancy F.

    2008-01-01

    Infectious myositis may be caused by a broad range of bacterial, fungal, parasitic, and viral agents. Infectious myositis is overall uncommon given the relative resistance of the musculature to infection. For example, inciting events, including trauma, surgery, or the presence of foreign bodies or devitalized tissue, are often present in cases of bacterial myositis. Bacterial causes are categorized by clinical presentation, anatomic location, and causative organisms into the categories of pyo...

  19. Non-infectious chemotherapy-associated acute toxicities during childhood acute lymphoblastic leukemia therapy

    DEFF Research Database (Denmark)

    Schmiegelow, Kjeld; Müller, Klaus Gottlob; Mogensen, Signe Sloth

    2017-01-01

    During chemotherapy for childhood acute lymphoblastic leukemia, all organs can be affected by severe acute side effects, the most common being opportunistic infections, mucositis, central or peripheral neuropathy (or both), bone toxicities (including osteonecrosis), thromboembolism, sinusoidal...... useful risk factors, and across study groups there has been wide diversity in toxicity definitions, capture strategies, and reporting, thus hampering meaningful comparisons of toxicity incidences for different leukemia protocols. Since treatment of acute lymphoblastic leukemia now yields 5-year overall...

  20. Treatment of acute sinusitis in childhood with ceftibuten.

    Science.gov (United States)

    Simon, M W

    1999-05-01

    Acute sinusitis is a common childhood illness. If it is overlooked or undertreated, suppurative and intracranial complications may develop. Amoxicillin has traditionally been the antibiotic of choice for treatment of acute sinusitis. However, the efficacy of amoxicillin has been reduced because of the emergence of bacteria producing b-lactamase and altered penicillin-binding proteins. This study compares the effectiveness of 10, 15, and 20 days of ceftibuten therapy with 14 days of erythromycin-sulfisoxazole therapy in treating acute sinusitis. The results indicate that both treatment regimens are effective in treating acute sinusitis (96% clinical response for erythromycin-sulfisoxazole vs 92% for a 10- or 15-day course of ceftibuten vs 100% for a 20-day course of ceftibuten). Longer treatment periods may be more effective in resolving the acute illness.

  1. Childhood vaccinations and risk of acute lymphoblastic leukaemia in children.

    Science.gov (United States)

    Søegaard, Signe Holst; Rostgaard, Klaus; Schmiegelow, Kjeld; Kamper-Jørgensen, Mads; Hargreave, Marie; Hjalgrim, Henrik; Hviid, Anders

    2017-06-01

    It has been proposed that childhood vaccinations protect against acute lymphoblastic leukaemia (ALL) in children by modulation of future responses to common infections in childhood. However, the available studies provide inconsistent findings, and population-based cohort studies with longitudinal information on vaccinations are lacking. In a register-based cohort of all children born in Denmark from 1 January 1990 to 31 December 2008, followed up until age 15 years or 31 December 2009 ( n  = 1 225 404), we evaluated exposure to childhood vaccination and risk of childhood ALL, including information on ALL subtypes. Using Cox regression, we estimated hazard ratios (HRs) comparing vaccinated with unvaccinated children. Childhood ALL was diagnosed in 490 children during 10 829 194 person-years of follow-up. Neither the total number of vaccine doses received nor exposure to each vaccination given in childhood was associated with altered risk of ALL, including the following: (i) Haemophilus influenzae type b [HR, 1.04; 95% confidence interval (CI), 0.68-1.61]; ii) measles, mumps and rubella (HR, 1.01; 95% CI, 0.76-1.34); iii) whole-cell pertussis (HR, 1.10; 95% CI, 0.51-2.39); and iv) diphtheria, tetanus and inactivated polio (HR, 1.14; 95% CI, 0.42-3.13). Analyses conducted according to ALL subtypes defined by immunopheno- and karyotypes showed no association with childhood vaccination. This nationwide cohort study provides no support of the proposed protective effect of childhood vaccination against childhood ALL.

  2. Childhood Acute Glomerulonepbritis in Benin City

    African Journals Online (AJOL)

    2000-12-31

    Dec 31, 2000 ... Haematuria and proteinuria of varying degrees occurred in all the patients, while antecedent infections were noted in 49.2 percent. Complications included congestive cardiac failure (39.7 percent), urinary tract infection (20.6 percent), acute renal failure (12.7 percent), and hypertensive encephalopathy.

  3. Acute transverse myelitis and acute disseminated encephalomyelitis in childhood: spectrum or separate entities?

    Science.gov (United States)

    Yiu, Eppie M; Kornberg, Andrew J; Ryan, Monique M; Coleman, Lee T; Mackay, Mark T

    2009-03-01

    The clinical and radiological features of childhood acute transverse myelitis are compared to those of acute disseminated encephalomyelitis with spinal cord involvement in 22 children with acute transverse myelitis and 12 children with acute disseminated encephalomyelitis with spinal cord involvement. Children with acute transverse myelitis were more likely to have a sensory level (55%) and areflexia. Sixty-eight percent of the children with acute transverse myelitis, and 92% of children with acute disseminated encephalomyelitis had longitudinally extensive transverse myelitis. Demyelination was more extensive in acute disseminated encephalomyelitis (mean 15.6 vertebral segments) than in acute transverse myelitis (mean 8.0 vertebral segments). The outcome was normal to good in 82% with acute transverse myelitis and in 100% with acute disseminated encephalomyelitis. Persistent bladder dysfunction was uncommon in both. Poor prognostic factors in acute transverse myelitis are flaccid paraparesis, respiratory failure, and age less than 6 months. These clinical and radiological differences suggest acute transverse myelitis and acute disseminated encephalomyelitis are separate entities.

  4. Childhood Acute Lymphoblastic Leukemia: Integrating Genomics into Therapy

    Science.gov (United States)

    Tasian, Sarah K; Loh, Mignon L; Hunger, Stephen P

    2015-01-01

    Acute lymphoblastic leukemia (ALL), the most common malignancy of childhood, is a genetically complex entity that remains a major cause of childhood cancer-related mortality. Major advances in genomic and epigenomic profiling during the past decade have appreciably enhanced knowledge of the biology of de novo and relapsed ALL and have facilitated more precise risk stratification of patients. These achievements have also provided critical insights regarding potentially targetable lesions for development of new therapeutic approaches in the era of precision medicine. This review delineates the current genetic landscape of childhood ALL with emphasis upon patient outcomes with contemporary treatment regimens, as well as therapeutic implications of newly identified genomic alterations in specific subsets of ALL. PMID:26194091

  5. Second Malignant Neoplasms After Treatment of Childhood Acute Lymphoblastic Leukemia

    DEFF Research Database (Denmark)

    Schmiegelow, K.; Levinsen, Mette Frandsen; Attarbaschi, Andishe

    2013-01-01

    PURPOSE: Second malignant neoplasms (SMNs) after diagnosis of childhood acute lymphoblastic leukemia (ALL) are rare events. PATIENTS AND METHODS: We analyzed data on risk factors and outcomes of 642 children with SMNs occurring after treatment for ALL from 18 collaborative study groups between 1980...... and 2007. RESULTS: Acute myeloid leukemia (AML; n = 186), myelodysplastic syndrome (MDS; n = 69), and nonmeningioma brain tumor (n = 116) were the most common types of SMNs and had the poorest outcome (5-year survival rate, 18.1% ± 2.9%, 31.1% ± 6.2%, and 18.3% ± 3.8%, respectively). Five-year survival...

  6. Relapsed childhood acute lymphoblastic leukemia in the Nordic countries

    DEFF Research Database (Denmark)

    Oskarsson, Trausti; Söderhäll, Stefan; Arvidson, Johan

    2016-01-01

    Relapse is the main reason for treatment failure in childhood acute lymphoblastic leukemia. Despite improvements in the up-front therapy, survival after relapse is still relatively poor, especially for high-risk relapses. The aims of this study were to assess outcomes following acute lymphoblastic...... leukemia relapse after common initial Nordic Society of Paediatric Haematology and Oncology protocol treatment; to validate currently used risk stratifications, and identify additional prognostic factors for overall survival. Altogether, 516 of 2735 patients (18.9%) relapsed between 1992 and 2011 and were...

  7. Magnetic resonance imaging of infectious myositis

    Energy Technology Data Exchange (ETDEWEB)

    Yun, Ji Young; Kim, Jee Young; Kim, Sang Heum; Jung, Youn Ju; Cha, Eun Suk; Park, Joung Mi; Park, Young Ha [The Catholic Univ., College of Medicine, Suwon (Korea, Republic of)

    1998-09-01

    To describe the findings of magnetic resonance imaging in infectious myositis and to determine their value for differentiation between ruberculous and bacterial myositis. Magnetic resonance images of ten proven cases of infectious myositis (five tuberculous and five bacterial) were retrospectively reviewed in the light of clinical and laboratory findings. On the basis of magnetic resonance images, signal intensity of the mass, the presence or absence of an abscess, signal intensity of the peripheral wall, patterns of contrast enhancement, and associated findings were evaluated. Compared with those of bacterial myositis, the symptoms of tuberculous myositis lasted longer but there were no difinite local inflammatory signs. In three of five cases of bacterial myositis there were specific medical records;trauma in two cases and systemic lupus erythematosus in one. All tuberculous myositis cases involved a single muscle, but bacterial myositis affected multipe muscles in three cases(60%). All but one case showed a mass in the involved muscles. In one bacterial case, there was diffuse swelling in the involved muscle. On T1-weighted images, eight infectious cases showed low signal intensity;two, of the bactrerial type, showed subtle increased signal intensity. all cases demonstrated high signal intensity on t2-weighted images. The signal intensity of peripheral wall was slightly increased on T1-weighted images, but low on T2-weighted. In four cases there was associated cellulitis, and in one case each, adjacent joint effusion and deep vein thrombosis were seen. After gadolinium infusion, peripheral rim enhancement was noted in nine cases and heterogeneous enhancement in one. After magnetic resonance imaging of infectious myositis, the characteristic finding was an abscessed lesion, with the peripheral wall showing high signal intensity on T1-weighted images and low signal intensity on T2 weighted. Although we found it difficult to differentiate bacterial from tuberculous

  8. Ophthalmic manifestations of relapsing acute childhood leukemia.

    Science.gov (United States)

    Chocron, Isaac M; Morrison, David G; Friedman, Debra L; Desai, Neerav A; Donahue, Sean P

    2015-06-01

    Acute lymphoblastic leukemia is the most common malignancy in children. We report 3 patients who presented to their general pediatricians and pediatric oncologists with ocular complaints as the only evidence of their leukemic relapses. All patients presented with persistent conjunctival injection and were referred to an ophthalmologist for further management. Two patients were diagnosed with recurrent anterior uveitis, which after extensive workup and treatment with topical glucocorticoids was found to be a result of leukemic ocular disease. One patient had a conjunctival tumor, which was biopsied and confirmed to be leukemic infiltration. All children eventually succumbed to their recurrent disease. These cases demonstrate the need for a high index of suspicion when evaluating ocular symptoms in patients with a prior history of acute lymphoblastic leukemia. Anterior chamber paracentesis and biopsy of suspicious lesions should be considered as possible diagnostic procedures in addition to standard hematologic studies. Collaboration between a primary care physician, pediatric oncologist, and ophthalmologist is essential for optimal diagnosis and treatment. Copyright © 2015 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.

  9. Childhood acute bacterial meningitis: risk factors for acute neurological complications and neurological sequelae.

    Science.gov (United States)

    Antoniuk, Sérgio A; Hamdar, Fátima; Ducci, Renata D; Kira, Ariane T F; Cat, Mônica N L; Cruz, Cristina R da

    2011-01-01

    To assess acute neurological complications and neurological sequelae of childhood acute bacterial meningitis in order to determine possible warning signs. This retrospective study evaluated children with acute bacterial meningitis (between 1 month and 14 years of age) admitted between 2003 and 2006. Of the 44 patients studied, 17 (38.6%) had acute neurological complications. Seizure was the most frequent (31.8%) complication. Patients with acute neurological complications showed a higher frequency of lower neutrophil count (p = 0.03), seizure at admission (p 200 mg/dL (p < 0.01), and cerebrospinal fluid glucose concentration/glycemia ratio (p < 0.01) were identified as risk variables for sequelae. Neutrophil count < 60%, seizure at admission, and S. pneumoniae as the etiologic agent were identified as warning signs for acute neurological complications, while protein levels, cerebrospinal fluid glucose concentration/glycemia ratio, and seizure at admission were seen as risk factors for neurological sequelae.

  10. Nanoparticle targeted therapy against childhood acute lymphoblastic leukemia

    Science.gov (United States)

    Satake, Noriko; Lee, Joyce; Xiao, Kai; Luo, Juntao; Sarangi, Susmita; Chang, Astra; McLaughlin, Bridget; Zhou, Ping; Kenney, Elaina; Kraynov, Liliya; Arnott, Sarah; McGee, Jeannine; Nolta, Jan; Lam, Kit

    2011-06-01

    The goal of our project is to develop a unique ligand-conjugated nanoparticle (NP) therapy against childhood acute lymphoblastic leukemia (ALL). LLP2A, discovered by Dr. Kit Lam, is a high-affinity and high-specificity peptidomimetic ligand against an activated α4β1 integrin. Our study using 11 fresh primary ALL samples (10 precursor B ALL and 1 T ALL) showed that childhood ALL cells expressed activated α4β1 integrin and bound to LLP2A. Normal hematopoietic cells such as activated lymphocytes and monocytes expressed activated α4β1 integrin; however, normal hematopoietic stem cells showed low expression of α4β1 integrin. Therefore, we believe that LLP2A can be used as a targeted therapy for childhood ALL. The Lam lab has developed novel telodendrimer-based nanoparticles (NPs) which can carry drugs efficiently. We have also developed a human leukemia mouse model using immunodeficient NOD/SCID/IL2Rγ null mice engrafted with primary childhood ALL cells from our patients. LLP2A-conjugated NPs will be evaluated both in vitro and in vivo using primary leukemia cells and this mouse model. NPs will be loaded first with DiD near infra-red dye, and then with the chemotherapeutic agents daunorubicin or vincristine. Both drugs are mainstays of current chemotherapy for childhood ALL. Targeting properties of LLP2A-conjugated NPs will be evaluated by fluorescent microscopy, flow cytometry, MTS assay, and mouse survival after treatment. We expect that LLP2A-conjugated NPs will be preferentially delivered and endocytosed to leukemia cells as an effective targeted therapy.

  11. Acute pancreatitis as a complication of childhood cancer treatment.

    Science.gov (United States)

    Stefanović, Milica; Jazbec, Janez; Lindgren, Fredrik; Bulajić, Milutin; Löhr, Matthias

    2016-05-01

    Acute pancreatitis (AP) is now well recognized as a possible complication of childhood cancer treatment, interrupting the chemotherapy regimen, and requiring prolonged hospitalization, possibly with intensive care and surgical intervention, thereby compromising the effect of chemotherapy and the remission of the underlying malignant disease. This review summarizes the current literature and presents the various etiological factors for AP during chemotherapy as well as modern trends in the diagnosis and therapy of AP in children. © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  12. Relapsed childhood acute lymphoblastic leukemia in the Nordic countries

    DEFF Research Database (Denmark)

    Oskarsson, Trausti; Söderhäll, Stefan; Arvidson, Johan

    2016-01-01

    leukemia relapse after common initial Nordic Society of Paediatric Haematology and Oncology protocol treatment; to validate currently used risk stratifications, and identify additional prognostic factors for overall survival. Altogether, 516 of 2735 patients (18.9%) relapsed between 1992 and 2011 and were......Relapse is the main reason for treatment failure in childhood acute lymphoblastic leukemia. Despite improvements in the up-front therapy, survival after relapse is still relatively poor, especially for high-risk relapses. The aims of this study were to assess outcomes following acute lymphoblastic...... included in the study. There were no statistically significant differences in outcome between the up-front protocols or between the relapse protocols used, but an improvement over time was observed. The 5-year overall survival for patients relapsing in the period 2002-2011 was 57.5±3.4%, but 44.7±3.2% (P...

  13. Non-infectious chemotherapy-associated acute toxicities during childhood acute lymphoblastic leukemia therapy

    Science.gov (United States)

    Schmiegelow, Kjeld; Müller, Klaus; Mogensen, Signe Sloth; Mogensen, Pernille Rudebeck; Wolthers, Benjamin Ole; Stoltze, Ulrik Kristoffer; Tuckuviene, Ruta; Frandsen, Thomas

    2017-01-01

    During chemotherapy for childhood acute lymphoblastic leukemia, all organs can be affected by severe acute side effects, the most common being opportunistic infections, mucositis, central or peripheral neuropathy (or both), bone toxicities (including osteonecrosis), thromboembolism, sinusoidal obstruction syndrome, endocrinopathies (especially steroid-induced adrenal insufficiency and hyperglycemia), high-dose methotrexate-induced nephrotoxicity, asparaginase-associated hypersensitivity, pancreatitis, and hyperlipidemia. Few of the non-infectious acute toxicities are associated with clinically useful risk factors, and across study groups there has been wide diversity in toxicity definitions, capture strategies, and reporting, thus hampering meaningful comparisons of toxicity incidences for different leukemia protocols. Since treatment of acute lymphoblastic leukemia now yields 5-year overall survival rates above 90%, there is a need for strategies for assessing the burden of toxicities in the overall evaluation of anti-leukemic therapy programs. PMID:28413626

  14. Daycare attendance and risk of childhood acute lymphoblastic leukaemia

    Science.gov (United States)

    Ma, X; Buffler, P A; Selvin, S; Matthay, K K; Wiencke, J K; Wiemels, J L; Reynolds, P

    2002-01-01

    The relationship between daycare/preschool (‘daycare’) attendance and the risk of acute lymphoblastic leukaemia was evaluated in the Northern California Childhood Leukaemia Study. Incident cases (age 1–14 years) were rapidly ascertained during 1995–1999. Population-based controls were randomly selected from the California birth registry, individually matched on date of birth, gender, race, Hispanicity, and residence, resulting in a total of 140 case–controls pairs. Fewer cases (n=92, 66%) attended daycare than controls (n=103, 74%). Children who had more total child–hours had a significantly reduced risk of ALL. The odds ratio associated with each thousand child–hours was 0.991 (95% confidence interval (CI): 0.984–0.999), which means that a child with 50 thousand child–hours (who may have, for example, attended a daycare with 15 other children, 25 h per week, for a total duration of 30.65 months) would have an odds ratio of (0.991)50=0.64 (95% CI: 0.45, 0.95), compared to children who never attended daycare. Besides, controls started daycare at a younger age, attended daycare for longer duration, remained in daycare for more hours, and were exposed to more children at each daycare. These findings support the hypothesis that delayed exposure to common infections plays an important role in the aetiology of childhood acute lymphoblastic leukaemia, and suggest that extensive contact with other children in a daycare setting is associated with a reduced risk of acute lymphoblastic leukaemia. British Journal of Cancer (2002) 86, 1419–1424. DOI: 10.1038/sj/bjc/6600274 www.bjcancer.com © 2002 Cancer Research UK PMID:11986774

  15. Childhood acute leukemias are frequent in Mexico City: descriptive epidemiology.

    Science.gov (United States)

    Pérez-Saldivar, María Luisa; Fajardo-Gutiérrez, Arturo; Bernáldez-Ríos, Roberto; Martínez-Avalos, Armando; Medina-Sanson, Aurora; Espinosa-Hernández, Laura; Flores-Chapa, José de Diego; Amador-Sánchez, Raquel; Peñaloza-González, José Gabriel; Alvarez-Rodríguez, Francisco Javier; Bolea-Murga, Victoria; Flores-Lujano, Janet; Rodríguez-Zepeda, María Del Carmen; Rivera-Luna, Roberto; Dorantes-Acosta, Elisa María; Jiménez-Hernández, Elva; Alvarado-Ibarra, Martha; Velázquez-Aviña, Martha Margarita; Torres-Nava, José Refugio; Duarte-Rodríguez, David Aldebarán; Paredes-Aguilera, Rogelio; Del Campo-Martínez, María de Los Ángeles; Cárdenas-Cardos, Rocío; Alamilla-Galicia, Paola Hillary; Bekker-Méndez, Vilma Carolina; Ortega-Alvarez, Manuel Carlos; Mejia-Arangure, Juan Manuel

    2011-08-17

    Worldwide, acute leukemia is the most common type of childhood cancer. It is particularly common in the Hispanic populations residing in the United States, Costa Rica, and Mexico City. The objective of this study was to determine the incidence of acute leukemia in children who were diagnosed and treated in public hospitals in Mexico City. Included in this study were those children, under 15 years of age and residents of Mexico City, who were diagnosed in 2006 and 2007 with leukemia, as determined by using the International Classification of Childhood Cancer. The average annual incidence rates (AAIR), and the standardized average annual incidence rates (SAAIR) per million children were calculated. We calculated crude, age- and sex-specific incidence rates and adjusted for age by the direct method with the world population as standard. We determined if there were a correlation between the incidence of acute leukemias in the various boroughs of Mexico City and either the number of agricultural hectares, the average number of persons per household, or the municipal human development index for Mexico (used as a reference of socio-economic level). Although a total of 610 new cases of leukemia were registered during 2006-2007, only 228 fit the criteria for inclusion in this study. The overall SAAIR was 57.6 per million children (95% CI, 46.9-68.3); acute lymphoblastic leukemia (ALL) was the most frequent type of leukemia, constituting 85.1% of the cases (SAAIR: 49.5 per million), followed by acute myeloblastic leukemia at 12.3% (SAAIR: 6.9 per million), and chronic myeloid leukemia at 1.7% (SAAIR: 0.9 per million). The 1-4 years age group had the highest SAAIR for ALL (77.7 per million). For cases of ALL, 73.2% had precursor B-cell immunophenotype (SAAIR: 35.8 per million) and 12.4% had T-cell immunophenotype (SAAIR 6.3 per million). The peak ages for ALL were 2-6 years and 8-10 years. More than half the children (58.8%) were classified as high risk. There was a positive

  16. Childhood acute leukemias are frequent in Mexico City: descriptive epidemiology

    Directory of Open Access Journals (Sweden)

    Bekker-Méndez Vilma

    2011-08-01

    Full Text Available Abstract Background Worldwide, acute leukemia is the most common type of childhood cancer. It is particularly common in the Hispanic populations residing in the United States, Costa Rica, and Mexico City. The objective of this study was to determine the incidence of acute leukemia in children who were diagnosed and treated in public hospitals in Mexico City. Methods Included in this study were those children, under 15 years of age and residents of Mexico City, who were diagnosed in 2006 and 2007 with leukemia, as determined by using the International Classification of Childhood Cancer. The average annual incidence rates (AAIR, and the standardized average annual incidence rates (SAAIR per million children were calculated. We calculated crude, age- and sex-specific incidence rates and adjusted for age by the direct method with the world population as standard. We determined if there were a correlation between the incidence of acute leukemias in the various boroughs of Mexico City and either the number of agricultural hectares, the average number of persons per household, or the municipal human development index for Mexico (used as a reference of socio-economic level. Results Although a total of 610 new cases of leukemia were registered during 2006-2007, only 228 fit the criteria for inclusion in this study. The overall SAAIR was 57.6 per million children (95% CI, 46.9-68.3; acute lymphoblastic leukemia (ALL was the most frequent type of leukemia, constituting 85.1% of the cases (SAAIR: 49.5 per million, followed by acute myeloblastic leukemia at 12.3% (SAAIR: 6.9 per million, and chronic myeloid leukemia at 1.7% (SAAIR: 0.9 per million. The 1-4 years age group had the highest SAAIR for ALL (77.7 per million. For cases of ALL, 73.2% had precursor B-cell immunophenotype (SAAIR: 35.8 per million and 12.4% had T-cell immunophenotype (SAAIR 6.3 per million. The peak ages for ALL were 2-6 years and 8-10 years. More than half the children (58.8% were

  17. Childhood Acute Bacterial Meningitis: Clinical Spectrum, Bacteriological Profile and Outcome.

    Science.gov (United States)

    Bari, Attia; Zeeshan, Fatima; Zafar, Aiza; Ejaz, Hassan; Iftikhar, Aisha; Rathore, Ahsan Waheed

    2016-10-01

    To determine the disease pattern, etiological agents and outcome of childhood acute bacterial meningitis. Adescriptive study. Department of Paediatric Medicine, The Children's Hospital, Lahore, from January to December 2012. Atotal of 199 children between the ages of 1 month and 5 years, admitted with the diagnosis of meningitis on the basis of clinical findings and positive cerebrospinal fluid (CSF), were included. In all patients, complete blood count (CBC), CSF culture sensitivity, and blood culture sensitivity were performed. Data was analysed using SPSS version 20. Out of 199 children, 127 (63.8%) were males with M:F ratio of 1.7:1. Mean age was 11.33 ±12 months. Maximum numbers of children were bacterial meningitis mostly affected children under the age of 1 year. CSF culture revealed both Grampositive and Gram-negative bacteria. The most common pathogen in children who died was streptococcus pneumoniae.

  18. [Prehospital management of acute childhood poisoning in Spain].

    Science.gov (United States)

    Salazar, June; Zubiaur, Oihane; Azkunaga, Beatriz; Molina, Juan Carlos; Mintegi, Santiago

    2017-06-01

    This objective was to analyze prehospital management of acute childhood poisonings. Poisonings treated in 59 pediatric emergency departments participating in the Toxicology Observation Project of the Spanish Society of Pediatric Emergency Medicine were registered prospectively between 2008 and 2014. We analyzed consultations made and treatments received before the patient arrived in the emergency department. A total of 902 poisonings were registered; in 870 cases (96.4%) cases whether or not a prehospital consultation had been made was on record. An emergency service of come type was contacted or visited in 312 cases (35.9%). Calls were most often made to the central emergency service (122 cases [14%]), primary care centers (100 cases [11.5%]), or the National Toxicology Institute (60 cases, [6.9%]). Choice of service to call or visit varied greatly according to type of poisoning. Prehospital treatment was more often received if a service had been contacted (26.3%) than if not (6.8%) (Pprehospital service had been contacted. About half the cases that consulted a poisoning service but did not receive treatment before coming to a hospital did receive treatment in the hospital emergency department. We conclude that a substantial percentage of patients who seek care for childhood poisoning from an emergency department have also consulted a prehospital service. Better prehospital management of such cases could facilitate earlier treatment when required and also preempt unnecessary trips to pediatric emergency departments.

  19. Necrotising Myositis, the Deadly Impersonator

    Directory of Open Access Journals (Sweden)

    A. Rahman

    2014-01-01

    Full Text Available We report two cases of patients with necrotising myositis who presented initially with limb pain and swelling on a background of respiratory complaints. Patient 1, a previously well 38-year-old female, underwent various investigations in the emergency department for excessive lower limb pain and a skin rash. Patient 2, a 61-year-old female with a background of rheumatoid arthritis and hypertension, presented to accident and emergency feeling generally unwell and was treated for presumed respiratory sepsis. Both deteriorated rapidly and were referred to the plastic surgery team with soft tissue necrosis, impending multiorgan failure and toxaemia. Large areas of necrotic muscle and skin were debrided, which grew group A streptococci, Streptococcus pyogenes. Patient 1 had a high above knee amputation of the left leg with extensive debridement of the right. Despite aggressive surgical intervention and microbiological input with intensive care support, patient 2 died. These two cases highlight the importance of early diagnosis and prompt surgical and pharmacological intervention in managing this life-threatening disease. Pain is the primary symptom with skin changes being a late and subtle sign in a septic patient. The Laboratory Risk Indicator for Necrotising Fasciitis (LRINEC may be of use if there is concern to aid diagnosis of this life-threatening disease.

  20. Cytogenetic Profile and Gene Mutations of Childhood Acute Lymphoblastic Leukemia

    Directory of Open Access Journals (Sweden)

    Nawaf Alkhayat

    2017-07-01

    Full Text Available Background: Childhood acute lymphoblastic leukemia (ALL is characterized by recurrent genetic aberrations. The identification of those abnormalities is clinically important because they are considered significant risk-stratifying markers. Aims: There are insufficient data of cytogenetic profiles in Saudi Arabian patients with childhood ALL leukemia. We have examined a cohort of 110 cases of ALL to determine the cytogenetic profiles and prevalence of FLT3 mutations and analysis of the more frequently observed abnormalities and its correlations to other biologic factors and patient outcomes and to compare our results with previously published results. Materials and methods: Patients —We reviewed all cases from 2007 to 2016 with an established diagnosis of childhood ALL. Of the 110 patients, 98 were B-lineage ALL and 12 T-cell ALL. All the patients were treated by UKALL 2003 protocol and risk stratified according previously published criteria. Cytogenetic analysis —Chromosome banding analysis and fluorescence in situ hybridization were used to detect genetic aberrations. Analysis of FLT3 mutations —Bone marrow or blood samples were screened for FLT3 mutations (internal tandem duplications, and point mutations, D835 using polymerase chain reaction methods. Result: Cytogenetic analysis showed chromosomal anomalies in 68 out of 102 cases with an overall incidence 66.7%. The most frequent chromosomal anomalies in ALL were hyperdiploidy, t(9;22, t(12;21, and MLL gene rearrangements. Our data are in accordance with those published previously and showed that FLT3 mutations are not common in patients with ALL (4.7% and have no prognostic relevance in pediatric patients with ALL. On the contrary, t(9;22, MLL gene rearrangements and hypodiploidy were signs of a bad prognosis in childhood ALL with high rate of relapse and shorter overall survival compared with the standard-risk group ( P  = .031.The event-free survival was also found to be worse ( P

  1. Targeting FLT3 Signaling in Childhood Acute Myeloid Leukemia

    Directory of Open Access Journals (Sweden)

    Amy N. Sexauer

    2017-11-01

    Full Text Available Acute myeloid leukemia (AML is the second most common leukemia of childhood and is associated with high rates of chemotherapy resistance and relapse. Clinical outcomes for children with AML treated with maximally intensive multi-agent chemotherapy lag far behind those of children with the more common acute lymphoblastic leukemia, demonstrating continued need for new therapeutic approaches to decrease relapse risk and improve long-term survival. Mutations in the FMS-like tyrosine kinase-3 receptor gene (FLT3 occur in approximately 25% of children and adults with AML and are associated with particularly poor prognoses. Identification and development of targeted FLT3 inhibitors represents a major precision medicine paradigm shift in the treatment of patients with AML. While further development of many first-generation FLT3 inhibitors was hampered by limited potency and significant toxicity due to effects upon other kinases, the more selective second- and third-generation FLT3 inhibitors have demonstrated excellent tolerability and remarkable efficacy in the relapsed/refractory and now de novo FLT3-mutated AML settings. While these newest and most promising inhibitors have largely been studied in the adult population, pediatric investigation of FLT3 inhibitors with chemotherapy is relatively recently ongoing or planned. Successful development of FLT3 inhibitor-based therapies will be essential to improve outcomes in children with this high-risk subtype of AML.

  2. Medical and Surgical Treatment in Pediatric Orbital Myositis Associated with Coxsackie Virus

    Directory of Open Access Journals (Sweden)

    Pedro Gil

    2015-01-01

    Full Text Available Purpose. To report a case of orbital myositis associated with Coxsackie virus and its medical and surgical approach. Methods. Complete ophthalmological examination and imaging and analytical investigation were performed. Results. A 6-year-old male presented with subacute painless binocular horizontal diplopia. Examination revealed bilateral best-corrected visual acuity (BCVA of 20/20 and right eye 45-prism-dioptre (PD esotropia in near and distance fixations, with no motility restrictions. Serologic screening was positive for Coxsackie virus acute infection and computerized tomography (CT suggested right eye medial rectus orbital myositis. An oral corticosteroid 1.0 mg/kg/day regimen was started. A new CT after two months showed symmetrical lesions in both medial rectus muscles. Corticosteroids were increased to 1.5 mg/kg/day. After imagiological resolution on the 4th month, alternating 45 PD esotropia persisted. Bilateral 7 mm medial rectus recession was performed after 1 year without spontaneous recovery. At 1-year follow-up, the patient is orthophoric with 200′′ stereopsis and bilateral 20/20 BCVA. Conclusions. To our knowledge, this is the first reported case of orbital myositis associated with Coxsackie virus. This is also the first reported case of isolated strabismus surgery after orbital myositis in pediatric age, highlighting the favourable aesthetic and functional outcomes even in cases of late ocular motility disorders.

  3. Cardiac function in survivors of childhood acute myeloid leukemia treated with chemotherapy only

    DEFF Research Database (Denmark)

    Jarfelt, Marianne; Andersen, Niels Holmark; Glosli, Heidi

    2015-01-01

    OBJECTIVES: We report cardiac function of patients treated for Childhood acute myeloid leukemia with chemotherapy only according to three consecutive Nordic protocols. METHODS: Ninety-eight of 138 eligible patients accepted examination with standardized echocardiography. Results were compared...

  4. High concordance of subtypes of childhood acute lymphoblastic leukemia within families

    DEFF Research Database (Denmark)

    Schmiegelow, K.; Thomsen, U Lautsen; Baruchel, A

    2012-01-01

    Polymorphic genes have been linked to the risk of acute lymphoblastic leukemia (ALL). Surrogate markers for a low burden of early childhood infections are also related to increased risk for developing childhood ALL. It remains uncertain, whether siblings of children with ALL have an increased risk...

  5. Decitabine in Treating Children With Relapsed or Refractory Acute Myeloid Leukemia or Acute Lymphoblastic Leukemia

    Science.gov (United States)

    2013-01-22

    Childhood Acute Myeloblastic Leukemia With Maturation (M2); Childhood Acute Promyelocytic Leukemia (M3); Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia

  6. Maternal coffee consumption during pregnancy and risk of childhood acute leukemia: a metaanalysis.

    Science.gov (United States)

    Cheng, Jian; Su, Hong; Zhu, Rui; Wang, Xu; Peng, Meiling; Song, Jian; Fan, Dongdong

    2014-02-01

    This study was undertaken to explore the association between maternal coffee consumption during pregnancy and childhood acute leukemia (AL). The PubMed database was used to search studies up to May 5, 2013, and the lists of references of retrieved articles were also screened to identify additional relevant studies. Studies were included if they reported the odds ratio and corresponding 95% confidence interval (CI) of childhood AL, including childhood acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML), with respect to maternal coffee consumption during pregnancy. Compared with non/lowest drinkers, the combined odds ratio regarding the relationship of maternal coffee consumption during pregnancy and childhood AL was 1.22 (95% CI, 1.04-1.43) for ever drinkers, 1.16 (95% CI, 1.00-1.34) for low to moderate-level drinkers, and 1.72 (95% CI, 1.37-2.16) for high-level drinkers. When analysis was conducted by subtypes of childhood AL, maternal coffee consumption (high-level drinkers vs non/lowest drinkers) was statistically significantly associated with childhood ALL (1.65; 95% CI, 1.28-2.12) and childhood AML (1.58; 95% CI, 1.20-2.08). We observed the linear dose-response relationship of coffee consumption and childhood AL (P for nonlinearity = .68), including childhood ALL and childhood AML; with increased coffee consumption, the risk of childhood AL increased. The findings of the metaanalysis suggest that maternal coffee consumption during pregnancy may increase the risk of childhood AL. Because of limited studies, further prospective studies are urgently needed to explore the adverse effect of coffee consumption on childhood AL. Copyright © 2014 Mosby, Inc. All rights reserved.

  7. Inclusion body myositis : a nationwide study

    NARCIS (Netherlands)

    Badrising, Umesh Arvind

    2006-01-01

    The studies reported in this thesis aimed to survey the prevalence of inclusion body myositis (IBM), to describe its clinical features and course, to investigate whether the major histocompatibility complex predisposed subjects to IBM and autoimmune disorders (AID), to investigate the possible

  8. 5. Myositis Ossificans – Two Case Presentations

    African Journals Online (AJOL)

    Esem

    The incidence rate is 2% following closed treatment of hip dislocation and increased to 34% when open. 2 reduction is required. Other common posttrauma myositis ossificans are the upper arm, calf, and sole. 2 of the foot. In our two patients the neck/head areas were free from this pathology; however the areas of affection.

  9. Personalization of dexamethasone therapy in childhood acute lymphoblastic leukaemia.

    Science.gov (United States)

    Jackson, Rosanna K; Irving, Julie A E; Veal, Gareth J

    2016-04-01

    Dexamethasone is a key component in the treatment of childhood acute lymphoblastic leukaemia (ALL). Despite playing a key role in the improved survival of ALL over several decades, intensification of dexamethasone therapy has also contributed to the increased toxicity associated with treatment, which is now seen to be at unacceptable levels given the favourable disease prognosis. Therefore the focus for treatment is now shifting towards reducing toxicity whilst maintaining current survival rates. As approximately 50% of patients were successfully treated on less intensive protocols of the 1980s, it has been questioned whether therapy intensification is necessary in all patients. Furthermore, there remains a subset of children who are still not cured of their disease. New strategies are therefore needed to identify patients who could benefit from dose reduction or intensification. However, adjusting a potentially life threatening therapy is a challenging task, particularly given the heterogeneous nature of ALL. This review focuses on the potential for patient stratification based on our current knowledge of dexamethasone pharmacokinetics, pharmacogenetics and the action of dexamethasone at the cellular level. A carefully designed, combined approach is needed if we are to achieve the aim of improved personalization of dexamethasone therapy for future patients. © 2016 John Wiley & Sons Ltd.

  10. Miosite e rabdomiólise na doença mão-pé-boca na infância Myositis and rhabdomyolysis in hand-foot-mouth disease in childhood

    Directory of Open Access Journals (Sweden)

    Maria Helena Vaisbich

    2010-03-01

    Full Text Available OBJETIVO: Relatar um caso de doença mão-pé-boca complicada por miosite, rabdomiólise e hepatite, interessante por ser a doença frequente em crianças e poder apresentar complicações graves, apesar de raras. DESCRIÇÃO DO CASO: Paciente de três anos de idade, sexo feminino, com história de febre por três dias, seguida pelo aparecimento de lesões ulceradas em mucosa oral e mialgia intensa. Após três dias, voltou a apresentar febre por mais dois dias (febre bifásica. Nesses dois dias, apresentou lesões eritematosas pelo corpo, principalmente nos pés, mãos e face, e procurou atendimento médico. Evoluiu com aumento de enzimas musculares e hepáticas (CPK com valor máximo de 345.007U/L, TGO 2041U/L, TGP 1589U/L, gama-GT 94U/L e aumento transitório da creatinina sérica, com clearance de creatinina estimado pela estatura de 73mL/minuto/1,73m2 de superfície corporal. Houve melhora progressiva, com hidratação vigorosa e alcalinização da urina, sem necessidade de diálise. COMENTÁRIOS: Trata-se de uma criança com doença mão-pé-boca, com miosite, rabdomiólise e hepatite. São enfatizados os critérios clínicos laboratoriais para o diagnóstico e a importância da monitorização das complicações da doençaOBJECTIVE: To report a hand-foot-mouth disease case, complicated by myositis, rhabdomyolisis and hepatitis, since this is a common disease in children and can result in rare but severe complications. CASE DESCRIPTION: A three-year-old girl with fever for three days, followed by the appearance of ulcerative lesions in the oral mucosa and severe muscular pain; after three days, she presented fever for two more days. At the same time, she had widespread erythematosus rash, especially in her hands, feet and face. She presented high levels of muscular and hepatic enzymes (maximum value of CPK 345.007IU/L, AST 2041IU/L, ALT 1589IU/L, GT 94IU/L, and transitory increase in serum creatinine (maximum value of 0.73mg/dL, creatinine

  11. Inclusion body myositis with granuloma formation in muscle tissue.

    Science.gov (United States)

    Sakai, Kenji; Ikeda, Yoshihisa; Ishida, Chiho; Matsumoto, Yasuko; Ono, Kenjiro; Iwasa, Kazuo; Yamada, Masahito

    2015-09-01

    Inclusion body myositis is a form of inflammatory myopathy. We identified 4 cases of inclusion body myositis showing granuloma formation in muscle tissue and aimed to assess the features of this atypical form of inclusion body myositis. We retrospectively reviewed consecutive patients who satisfied European Neuromuscular Centre IBM Research Diagnostic Criteria 2011. Then, we assessed clinical profiles and pathological findings in patients with inclusion body myositis with granuloma and compared these findings with those of typical inclusion body myositis without granuloma. We identified 15 patients with inclusion body myositis. Four patients showed granuloma formation in muscle tissue in addition to typical pathological features of inclusion body myositis. Granulomas comprised a mixture of inflammatory cells, such as macrophages, epithelioid histiocytic cells, and lymphocytes. One patient was found to have mediastinal granulomatous lymphadenopathy; however, the evidence in other patients was insufficient for a diagnosis of systemic sarcoidosis. There were no significant differences between groups with and without granuloma regarding clinical manifestations, laboratory findings, response to immunomodulating therapies, or myopathological profiles. We established a new form of inclusion body myositis showing granuloma formation in muscle tissue. Inclusion body myositis and granuloma formation could have identical pathomechanisms concerning dysregulation of autophagy. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Dermatomyositis Sine Myositis with Membranoproliferative Glomerulonephritis

    Directory of Open Access Journals (Sweden)

    Mohammad Bagher Owlia

    2012-01-01

    Full Text Available Dermatomyositis (DM is an autoimmune disease that is characterized by involvement of proximal musculature and skin. We report a 52-year-old woman with a 6-year history of dermatomyositis sine myositis, who developed lower extremity edema and proteinuria. Pathological examination of renal biopsy showed membranoproliferative glomerulonephritis. She received steroid, cyclophosphamide, and mycophenolate mofetil. Over the 9 to 10 months after the beginning of treatment, the proteinuria was improved.

  13. [Myositis ossificans circumscripta and its variants].

    Science.gov (United States)

    Wybier, M; Quillard, A; Parlier, C; Champsaur, P

    1997-01-01

    Myositis ossificans circumscripta (MOC) is a benign proliferation of fibrous tissue with large amounts of bone within soft tissues. Its clinical and radiological course is described and the value of CT and MR imaging is emphasized. Differential diagnosis includes soft tissue hematoma, infection or tumor. Florid reactive periostitis of the phalanges, turret exostosis, bizarre periosteal osteochondromatous proliferation in the hand and fibro-osseous pseudotumor of the digits are also described.

  14. Myositis Ossificans Circumscripta of the Supra-orbital Region: A ...

    African Journals Online (AJOL)

    ANNALS

    report. The treatment of myositis ossificans is surgical excision13,15 of the lesion. The surgical approach of a bicoronal incision was to offer us a wide surgical field coupled with the absence of any facial scar or keloid post-operatively which is common in Africans. References. 1. Bullough PG. Vigorita VJ. Myositis ossificans.

  15. An atypical presentation of myositis ossificans | Bultheel | South ...

    African Journals Online (AJOL)

    An atypical presentation of myositis ossificans. M Bultheel, JH Kirby, JT Viljoen, PL Viviers. Abstract. In the following case study an atypical presentation of myositis ossificans (MO) in the superior anterolateral thigh of a young soccer player is discussed. This case demonstrates that MO can present without obvious history of ...

  16. MYOSITIS OSSIFICANS TRAUMATICA IN A VAMPIRE BAT (DESMODUS ROTUNDUS).

    Science.gov (United States)

    Hausmann, Jennifer C; Manasse, Jorden; Churgin, Sarah; Steinberg, Howard; Clyde, Victoria L; Wallace, Roberta

    2016-09-01

    A 15-yr-old sexually intact female vampire bat ( Desmodus rotundus ) was diagnosed with myositis ossificans traumatica of the abdominal wall. The bat presented with a large ulcerated firm mass along the abdomen. Radiographs and cytology were performed, followed by surgical exploration. The mass was determined to be nonresectable and the bat was euthanized. Histopathology showed severe necrotizing, degenerative, and pyogranulomatous myositis with osseous and cartilaginous metaplasia, fibrosis, and ulceration, which were consistent with myositis ossificans traumatica. Myositis ossificans traumatica is commonly associated with previous trauma to skeletal muscle. Two years prior, this bat had an emergency Caesarian section at this site, which was postulated to elicit a marked tissue response leading to this condition. Myositis ossificans traumatica is infrequently reported in humans, dogs, cats, pigs, and horses. To the author's knowledge, this is the first report of this condition in a bat.

  17. Ocular manifestations of childhood acute leukemia in a tertiiary level eye centre of Kathmandu, Nepal.

    Science.gov (United States)

    Khadka, Deepak; Sharma, Ananda K; Shrestha, Jeevan K; Shrestha, Gauri S; Shrestha, Pun N; Pant, Suresh R; Pant, Bidya P

    2014-01-01

    In some instances, the understanding of the ocular manifestations in childhood leukemia is not only important to establish the diagnosis but also reflects the disease state and prognosis. To study the ocular manifestations of childhood acute leukemia among the children attending a tertiary-level hospital in Nepal. A cross-sectional, descriptive study was undertaken at the B.P. Koirala Lions Centre for Ophthalmic Studies (BPKLCOS) and Kanti Children Hospital (KCH), Kathmandu, over a period of one-and-a-half years. Children diagnosed with acute childhood leukemia referred to the BPKLCOS from the Oncology Unit of the KCH and the Emergency Department of the Tribhuvan University Teaching Hospital (TUTH) were included in the study, using a non-probability sampling method. Of the 71 cases with childhood acute leukemia, 55 (77.5%; 95% CI = 66% - 85%) had acute lymphoblastic leukemia(ALL)whereas the other 16 (23%) had acute myeloblastic leukemia (AML). Ocular involvement were seen in 33 cases (46%) and were more frequent in cases of AML as compared to those with ALL (p=0.001, OR 5.0, 95% CI= 1.4 - 17.5). Direct ocular involvement and secondary ocular involvement were observed in 12 (16.9%) and 29 (40.8%) subjects, respectively. Ocular symptoms were present in only 11 cases (15.49%). Cerebro-spinal fluid (CSF) and bone marrow examination in cases with direct ocular involvement showed 10 cases (83.3%) positive for blast cells in the CSF and 6 cases (50%) positive for blast cells in bone marrow. The most common secondary manifestation was retinal haemorrhage, seen in 23 cases (32.4%). In view of the high asymptomatic ocular involvement and the significant visual morbidity, a routine ophthalmic examination is recommended as an integral part of the medical examination in all cases of childhood acute leukemia. © NEPjOPH.

  18. Pediatric nontraumatic myositis ossificans of the neck

    Energy Technology Data Exchange (ETDEWEB)

    Kokkosis, Angela A. [Stony Brook University Medical Center, Stony Brook University School of Medicine, Stony Brook, NY (United States); Balsam, Dvorah [Stony Brook University Medical Center, Department of Radiology, Stony Brook, NY (United States); Lee, Thomas K. [Stony Brook University Medical Center, Department of Pediatric Surgery, Stony Brook, NY (United States); Schreiber, Z.J. [Stony Brook University Medical Center, Department of Pathology, Stony Brook, NY (United States)

    2009-04-15

    Nontraumatic myositis ossificans circumscripta (MOC) is a rarely reported benign heterotopic ossification characterized by the aberrant formation of bone in extraskeletal soft tissues. Although a history of trauma can be elicited in 75% of MOC patients, the etiology is unclear in patients without inciting injury. MOC is associated with young male athletes, and is most often localized to the muscle groups of the extremities. Rare cases have been reported in children and adolescents of nontraumatic MOC in the neck. We present a 15-year-old adolescent with a rapidly growing, painful neck mass without traumatic stimulus. (orig.)

  19. Efficacy and Toxicity of Asparaginases During Prospective Drug Monitoring in Patients With Childhood Acute Lymphoblastic Leukemia

    NARCIS (Netherlands)

    W.H. Tong (Wing)

    2014-01-01

    markdownabstract__Abstract__ Intensified and effective asparaginase therapy is very important in modern treatment of childhood acute lymphoblastic leukemia. The use of native E.coli asparaginase in induction leads to a high rate of hypersensitivity reactions to PEGasparaginase in the

  20. Challenges in implementing individualized medicine illustrated by antimetabolite therapy of childhood acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Nersting, Jacob; Borst, Louise; Schmiegelow, Kjeld

    2011-01-01

    illustrated by studies involving childhood acute lymphoblastic leukemia (ALL), where each patient may receive up to 13 different anticancer agents over a period of 2-3 years. The challenges include i) addressing important, but low-frequency outcomes, ii) difficulties in interpreting the impact of single drug...

  1. Extremely low-frequency magnetic fields and survival from childhood acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Schüz, J; Grell, K; Kinsey, S

    2012-01-01

    A previous US study reported poorer survival in children with acute lymphoblastic leukemia (ALL) exposed to extremely low-frequency magnetic fields (ELF-MF) above 0.3 μT, but based on small numbers. Data from 3073 cases of childhood ALL were pooled from prospective studies conducted in Canada...

  2. Sleep, fatigue, depression, and quality of life in survivors of childhood acute lymphoblastic leukemia

    NARCIS (Netherlands)

    Gordijn, M.S.; van Litsenburg, R.R.L.; Gemke, R.J.; Huisman, J.; Bierings, M.B.; Hoogerbrugge, P.M.; Kaspers, G.J.L.

    2013-01-01

    Background: With the improved survival of childhood acute lymphoblastic leukemia (ALL), the effect of treatment on psychosocial well-being becomes increasingly relevant. Literature on sleep and fatigue during treatment is emerging. However, information on these subjects after treatment is sparse.

  3. Sleep, fatigue, depression, and quality of life in survivors of childhood acute lymphoblastic leukemia.

    NARCIS (Netherlands)

    Gordijn, M.S.; Litsenburg, R.R. van; Gemke, R.J.; Huisman, J.; Bierings, M.B.; Hoogerbrugge, P.M.; Kaspers, G.J.L.

    2013-01-01

    BACKGROUND: With the improved survival of childhood acute lymphoblastic leukemia (ALL), the effect of treatment on psychosocial well-being becomes increasingly relevant. Literature on sleep and fatigue during treatment is emerging. However, information on these subjects after treatment is sparse.

  4. Mutational analysis of Bax and Bcl-2 in childhood acute lymphoblastic leukaemia

    NARCIS (Netherlands)

    Salomons, G. S.; Buitenhuis, C. K.; Martínez Muñoz, C.; Verwijs-Jassen, M.; Behrendt, H.; Zsiros, J.; Smets, L. A.

    1998-01-01

    In childhood acute lymphoblastic leukaemia there are large interpatient variations in levels of the apoptosis-regulating proteins Bax and Bcl-2, but the molecular basis for this variation is unknown. Point-mutations in bax have been reported in cell lines derived from haematological malignancies.

  5. In childhood acute lymphoblastic leukemia, blasts at different stages of immunophenotypic maturation have stem cell properties

    NARCIS (Netherlands)

    le Viseur, Christoph; Hotfilder, Marc; Bomken, Simon; Wilson, Kerrie; Roettgers, Silja; Schrauder, Andre; Rosemann, Annegret; Irving, Julie; Stam, Ronald W.; Shultz, Leonard D.; Harbott, Jochen; Juergens, Heribert; Schrappe, Martin; Pieters, Rob; Vormoor, Josef

    We examined the leukemic stem cell potential of blasts at different stages of maturation in childhood acute lymphoblastic leukemia (ALL). Human leukemic bone marrow was transplanted intrafemorally into NOD/scid mice. Cells sorted using the B precursor differentiation markers CD19, CD20, and CD34

  6. Risk factors for treatment related mortality in childhood acute lymphoblastic leukaemia

    DEFF Research Database (Denmark)

    Lund, Bendik; Åsberg, Ann; Heyman, Mats

    2011-01-01

    BACKGROUND: In spite of major improvements in the cure rate of childhood acute lymphoblastic leukaemia (ALL), 2-4% of patients still die from treatment related complications. PROCEDURE: We investigated the pattern of treatment related deaths (TRDs) and possible risk factors in the NOPHO ALL-92 an...... towards patients at risk. Pediatr Blood Cancer. © 2010 Wiley-Liss, Inc....

  7. Childhood Acute Appenditis In Nnewi Nigeria | Osuigwe | Nigerian ...

    African Journals Online (AJOL)

    Nigerian Journal of Clinical Practice ... Acute appendicitis is not common in the paediatric age group in our environment and far more negative appendicectomies are performed. A scoring system for acute appendicitis in children in our environment is hereby advocated to reduce the incidence of negative appendectomy.

  8. Non-infectious chemotherapy-associated acute toxicities during childhood acute lymphoblastic leukemia therapy [version 1; referees: 3 approved

    Directory of Open Access Journals (Sweden)

    Kjeld Schmiegelow

    2017-04-01

    Full Text Available During chemotherapy for childhood acute lymphoblastic leukemia, all organs can be affected by severe acute side effects, the most common being opportunistic infections, mucositis, central or peripheral neuropathy (or both, bone toxicities (including osteonecrosis, thromboembolism, sinusoidal obstruction syndrome, endocrinopathies (especially steroid-induced adrenal insufficiency and hyperglycemia, high-dose methotrexate-induced nephrotoxicity, asparaginase-associated hypersensitivity, pancreatitis, and hyperlipidemia. Few of the non-infectious acute toxicities are associated with clinically useful risk factors, and across study groups there has been wide diversity in toxicity definitions, capture strategies, and reporting, thus hampering meaningful comparisons of toxicity incidences for different leukemia protocols. Since treatment of acute lymphoblastic leukemia now yields 5-year overall survival rates above 90%, there is a need for strategies for assessing the burden of toxicities in the overall evaluation of anti-leukemic therapy programs.

  9. Childhood Acute Lymphoblastic Leukemia Treatment (PDQ®)—Patient Version

    Science.gov (United States)

    Childhood ALL is a type of cancer in which the bone marrow makes too many immature lymphocytes (a type of white blood cell). Here’s what you need to know about the risk factors, signs, tests to diagnose, and treatment of newly diagnosed and recurrent ALL in this expert-reviewed summary.

  10. Mutations in LPIN1 cause recurrent acute myoglobinuria in childhood

    NARCIS (Netherlands)

    Zeharia, Avraham; Shaag, Avraham; Houtkooper, Riekelt H.; Hindi, Tareq; de Lonlay, Pascale; Erez, Gilli; Hubert, Laurence; Saada, Ann; de Keyzer, Yves; Eshel, Gideon; Vaz, Frédéric M.; Pines, Ophry; Elpeleg, Orly

    2008-01-01

    Recurrent episodes of life-threatening myoglobinuria in childhood are caused by inborn errors of glycogenolysis, mitochondrial fatty acid beta-oxidation, and oxidative phosphorylation. Nonetheless, approximately half of the patients do not suffer from a defect in any of these pathways. Using

  11. Acute necrotizing encephalopathy of childhood: typical findings in an atypical disease

    Energy Technology Data Exchange (ETDEWEB)

    Skelton, Brandon W.; Phillips, C.D. [University of Virginia Health System, Department of Neuroradiology, Charlottesville, VA (United States); Hollingshead, Michael C.; Castillo, Mauricio [University of North Carolina School of Medicine, Neuroradiology Section, Chapel Hill, NC (United States); Sledd, Andrew T. [University of Virginia Health System, Department of Pediatrics, Charlottesville, VA (United States)

    2008-07-15

    Acute necrotizing encephalopathy of childhood (ANEC) is a disease entity seen nearly exclusively in East Asian children that is characterized by multifocal, symmetric lesions involving the thalami, brainstem, cerebellum, and white matter. We present a child who developed dramatic neurologic symptoms following a viral prodrome. Serial MRI examinations demonstrated characteristic lesions of ANEC, while laboratory analyses revealed evidence of acute infection with human herpesvirus-6 (HHV-6). We highlight the MRI findings in both the acute and convalescent phases of ANEC, discuss the implications of neuroimaging on the child's clinical course, and emphasize the integral role of the radiologist in correctly diagnosing this rare disease. (orig.)

  12. Mutations in LPIN1 cause recurrent acute myoglobinuria in childhood.

    Science.gov (United States)

    Zeharia, Avraham; Shaag, Avraham; Houtkooper, Riekelt H; Hindi, Tareq; de Lonlay, Pascale; Erez, Gilli; Hubert, Laurence; Saada, Ann; de Keyzer, Yves; Eshel, Gideon; Vaz, Frédéric M; Pines, Ophry; Elpeleg, Orly

    2008-10-01

    Recurrent episodes of life-threatening myoglobinuria in childhood are caused by inborn errors of glycogenolysis, mitochondrial fatty acid beta-oxidation, and oxidative phosphorylation. Nonetheless, approximately half of the patients do not suffer from a defect in any of these pathways. Using homozygosity mapping, we identified six deleterious mutations in the LPIN1 gene in patients who presented at 2-7 years of age with recurrent, massive rhabdomyolysis. The LPIN1 gene encodes the muscle-specific phosphatidic acid phosphatase, a key enzyme in triglyceride and membrane phospholipid biosynthesis. Of six individuals who developed statin-induced myopathy, one was a carrier for Glu769Gly, a pathogenic mutation in the LPIN1 gene. Analysis of phospholipid content disclosed accumulation of phosphatidic acid and lysophospholipids in muscle tissue of the more severe genotype. Mutations in the LPIN1 gene cause recurrent rhabdomyolysis in childhood, and a carrier state may predispose for statin-induced myopathy.

  13. Causes of death - other than progressive leukemia - in childhood acute lymphoblastic (ALL) and myeloid leukemia (AML) : the Dutch Childhood Oncology Group experience

    NARCIS (Netherlands)

    Slats, AM; Egeler, RM; van der Does-van den Berg, A; Korbijn, C; Hahlen, K; Kamps, WA; Veerman, AJP; Zwaan, CM

    We analyzed causes of death, other than resistant disease or relapse, in 875 children with acute lymphoblastic leukemia ( ALL) and 229 with acute myeloid leukemia (AML), treated on three different Dutch Childhood Oncology Group (DCOG) ALL and three AML protocols. Overall, 23 (2.6%) ALL and 44

  14. Ploidy and clinical characteristics of childhood acute myeloid leukemia

    DEFF Research Database (Denmark)

    Sandahl, Julie Damgaard; Kjeldsen, Eigil; Abrahamsson, Jonas

    2014-01-01

    We report the first large series (n = 596) of pediatric acute myeloid leukemia (AML) focusing on modal numbers (MN) from the population-based NOPHO-AML trials. Abnormal karyotypes were present in 452 cases (76%) and numerical aberrations were present in 40% (n = 237) of all pediatric AML. Among...... with early onset (median age 2 years), female sex (57%), and a dominance of acute megakaryoblastic leukemia (AMKL) (29%). Hypodiploidy constituted 8% of all AML and was associated with older age (median age 9 years), male predominance (60%), FAB M2 (56%), and t(8;21)(q22;q22) (56%) with loss of sex...

  15. Tubuloreticular structures in different types of myositis: Implications for pathogenesis

    NARCIS (Netherlands)

    Bronner, I.M.; Hoogendijk, J.E.; Veldman, H.; Ramkema, M; Weerman, M.A.V.; Rozemuller, A.J.M.; Visser, M.

    2008-01-01

    In dermatomyositis (DM) there is strong histopathological evidence of a microvascular pathogenesis, including endothelial microtubular inclusions. In nonspecific myositis, perimysial and perivascular infiltrates in the muscle biopsy similar to DM are found. Microtubular inclusions in endothelial

  16. Tubuloreticular structures in different types of myositis: implications for pathogenesis

    NARCIS (Netherlands)

    Bronner, Irene M.; Hoogendijk, Jessica E.; Veldman, Henk; Ramkema, Marja; van den Bergh Weerman, Marius A.; Rozemuller, Annemieke J. M.; de Visser, Marianne

    2008-01-01

    In dermatomyositis (DM) there is strong histopathological evidence of a microvascular pathogenesis, including endothelial microtubular inclusions. In nonspecific myositis, perimysial and perivascular infiltrates in the muscle biopsy similar to DM are found. Microtubular inclusions in endothelial

  17. Childhood Acute Glomerulonephritis in Benin City | Ibadin | Nigerian ...

    African Journals Online (AJOL)

    Complications included congestive cardiac failure (39.7 percent), urinary tract infection (20.6 percent), acute renal failure (12.7 percent), and hypertensive encephalopathy (4.8 percent), while mortality was 3.2 percent. Two cases each, developed nephrotic syndrome and chronic renal failure after about two years of follow ...

  18. CHILDHOOD ACUTE Al?P'ENDICITIS IN NNEW'[, NIGERIA

    African Journals Online (AJOL)

    Acute appendicitis is not common in the peadiatric age group in our environment and far more negative appendicectomies are periioi med. A scoring system ... PATIENTS ANI) METHODS. Case notes of all appendicectomies done in the age group 15 ... eween ie "d an 'h eca es. so re )Ol'S rom e3,. -Nigeria showed that the ...

  19. Statin-induced autoimmune necrotizing myositis

    Directory of Open Access Journals (Sweden)

    Katarzyna Ząber

    2016-02-01

    Full Text Available Myositides comprise a large group of disorders involving limb muscle weakness. In differential diagnosis we have to consider idiopathic myositides, myositides associated with other diseases, and those induced by external factors, e.g. drug-induced. Statins are commonly used drugs, but many patients experience a broad spectrum of adverse effects including symptoms from skeletal muscle. Physicians should pay special attention to patients reporting muscle weakness lasting longer than 12 weeks, despite statin withdrawal, as well as other symptoms: dysphagia, disturbed grip function, elevated creatinine kinase (CK levels and abnormal electromyography. The reported case deals with the problem of differential diagnosis of drug-induced muscle injury, polymyositis with a recently reported myopathy – statin-induced autoimmune necrotizing myositis, related to anti-HMGCR antibodies.

  20. Maternal diabetes and risk of childhood acute lymphoblastic leukaemia in the offspring

    DEFF Research Database (Denmark)

    Søegaard, Signe Holst; Rostgaard, Klaus; Kamper-Jørgensen, Mads

    2018-01-01

    BACKGROUND: Maternal diabetes may be linked to childhood acute lymphoblastic leukaemia (ALL) in the offspring. METHODS: We assessed the association between maternal pregestational or gestational diabetes and offspring risk of childhood ALL in a register-based study, including all singletons born...... in Denmark during 1996-2015 (n=1 187 482). RESULTS: Adjusted hazard ratios of childhood ALL were 2.91 (95% confidence interval (CI): 1.30-6.51) for maternal pregestational diabetes and 1.75 (95% CI: 1.02-2.98) for maternal gestational diabetes. Paternal diabetes did not alter offspring ALL risk, and we found...... no association between offspring ALL and later maternal risk of diabetes. CONCLUSIONS: Regardless that absolute ALL risk among offspring of women with diabetes remains low, our findings suggest that characteristics of the diabetic intrauterine environment promote ALL development. This offers a setting for future...

  1. Does childhood misfortune raise the risk of acute myocardial infarction in adulthood?

    Science.gov (United States)

    Morton, Patricia M.; Mustillo, Sarah A.; Ferraro, Kenneth F.

    2014-01-01

    Whereas most research on acute myocardial infarction (AMI) has focused on more proximal influences, such as adult health behaviors, the present study examines the early origins of AMI. Longitudinal data were drawn from the National Survey of Midlife Development in the United States (N=3,032), a nationally representative survey of men and women aged 25–74, which spans from 1995 to 2005. A series of event history analyses modeling age of first AMI investigated the direct effects of accumulated and separate domains of childhood misfortune as well as the mediating effects of adult health lifestyle and psychosocial factors. Findings reveal that accumulated childhood misfortune and child maltreatment increased AMI risk, net of several adult covariates, including family history of AMI. Smoking fully mediated the effects of both accumulated childhood misfortune and child maltreatment. These findings reveal the importance of the early origins of AMI and health behaviors as mediating factors. PMID:24581071

  2. Cure rates of childhood acute lymphoblastic leukemia in Lithuania and the benefit of joining international treatment protocol

    DEFF Research Database (Denmark)

    Vaitkevičienė, Goda; Matuzevičienė, Rėda; Stoškus, Mindaugas

    2014-01-01

    BACKGROUND: Childhood acute lymphoblastic leukemia (ALL) represents the largest group of pediatric malignancies with long-term survival rates of more than 80% achieved in developed countries. Epidemiological data and survival rates of childhood ALL in Lithuania were lacking. Therefore, the aim of...

  3. The Eleventh International Childhood Acute Lymphoblastic Leukemia Workshop Report: Ponte di Legno, Italy, 6-7 May 2009

    DEFF Research Database (Denmark)

    Biondi, A; Baruchel, A; Hunger, S

    2009-01-01

    An international childhood acute lymphoblastic leukemia (ALL)working group was formed during the 27th annual meeting of the International Society of Pediatric Oncology in 1995. Since then, 10 workshops have been held to address many issues that help advance treatment outcome of childhood ALL...

  4. Compliance with a protocol for acute lymphoblastic leukemia in childhood

    Directory of Open Access Journals (Sweden)

    Benigna Maria de Oliveira

    2011-06-01

    Full Text Available BACKGROUND: Remission rates achieved after the initial treatment of acute lymphoblastic leukemia may be similar in both developed and developing countries, but relapse rates are much higher in the latter. Thus, other reasons are needed, in addition to biological characteristics of the leukemic cells themselves, to explain the unfavorable evolution of patients living in unfavorable socioeconomic and cultural conditions. OBJECTIVE: The aim of this study was to retrospectively evaluate compliance to an acute lymphoblastic leukemia treatment protocol. METHODS: Main abstracted data were: total duration and reasons for interruption of chemotherapy, prescribed doses of 6-mercaptopurine, and median white blood cell and neutrophil counts during the maintenance phase. Interruptions of chemotherapy were considered inappropriate if they did not follow predetermined criteria established in the protocol. RESULTS: Fourteen of 73 patients (19.2% unduly interrupted chemotherapy by determination of their physicians. The median white blood cell count was higher when compared with the protocol recommendations; the median 6-MP dose was lower than the standard recommended dose. The estimated probability of event-free survival was higher for patients with lower median leukocyte counts and close to those predetermined by the protocol. Event-free survival was also higher for children with a higher percentage of days without chemotherapy due to bone marrow or liver toxicity excluding undue interruptions. In multivariate analysis, both factors remained statistically significant. These results suggest that the intensity of maintenance chemotherapy may not have been enough in some children, to achieve adequate myelosuppression, hence the observation of higher leukocyte counts and none or rare episodes of therapy interruption. CONCLUSIONS: Compliance to the therapeutic protocol by both doctors and patients should always be considered in the evaluation of therapeutic failure

  5. Treatment-related mortality in relapsed childhood acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Oskarsson, Trausti; Söderhäll, Stefan; Arvidson, Johan

    2017-01-01

    . PROCEDURE: In this retrospective population-based study, we described the causes of death and estimated the risk for treatment-related mortality in patients with first relapse of childhood ALL in the Nordic Society of Paediatric Haematology and Oncology ALL-92 and ALL-2000 trials. RESULTS: Among the 483...... patients who received relapse treatment with curative intent, we identified 52 patients (10.8%) who died of treatment-related causes. Twelve of these died before achieving second remission and 40 died in second remission. Infections were the cause of death in 38 patients (73.1%), predominantly bacterial......, none of the 17 patients with Down syndrome died of treatment-related causes. CONCLUSIONS: Fatal treatment complications contribute significantly to the poor overall survival after relapse. Implementation of novel therapies with reduced toxicity and aggressive supportive care management are important...

  6. Probiotics use in childhood acute diarrhea: a web-based survey.

    Science.gov (United States)

    Weizman, Zvi

    2011-01-01

    To evaluate practices and barriers for the use of probiotics in acute diarrhea among pediatric gastroenterologists. Probiotics have shown significant therapeutic potential in acute infectious diarrhea. However, literature data regarding practice patterns in childhood are limited. A web-based 9-item survey among 1854 pediatric gastroenterologists worldwide. Only 634 (34%) responded. Forty-one were excluded owing to incomplete data. Finally 593, USA (n=407) and non-USA (n=186) participants, showed: limited use in acute diarrhea (28% and 32% prospectively), prescription of a 1 strain product only by 31% and 24%, respectively, and limited utilization in ambulatory settings (43% and 51%, respectively) and in prevention of diarrhea (2.6% and 3.4%, respectively). Most participants felt there is lack of useful clinical guidelines (91% and 84%, respectively), and found this therapy effective or very effective (54% and 62%, respectively). Dosing and duration were extremely variable, the youngest age treated ranged from 2 months to 2 years of age, and adverse effects were extremely rare. These characteristics were shared by USA and by non-USA participants, with no significant differences between groups (P>0.05). Many pediatric gastroenterologists worldwide do not use probiotics for acute diarrhea owing to lack of appropriate guidelines and/or poorly designed products. Therefore, worldwide health authorities should provide pharmaceutical and clinical guidelines for the appropriate use of probiotics in acute diarrhea of childhood.

  7. Late cardiac effects of anthracycline containing therapy for childhood acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Rathe, Mathias; Carlsen, Niels L T; Oxhøj, Henrik

    2007-01-01

    At present about 80% of children with acute lymphoblastic leukemia (ALL) will be cured following treatment with multi-drug chemotherapy. A major concern for this growing number of survivors is the risk of late effects of treatment. The aim of this study was to determine whether signs of cardiomyo...... of cardiomyopathy were present in patients treated in childhood with cumulative anthracycline doses of less than 300 mg/m(2)....

  8. Ras/Raf/MEK/ERK pathway activation in childhood acute lymphoblastic leukemia and its therapeutic targeting

    Directory of Open Access Journals (Sweden)

    Thomas eKnight

    2014-06-01

    Full Text Available Deregulation of the Ras/Raf/MEK/ERK pathway is a common event in childhood acute lymphoblastic leukemia and is caused by point mutation, gene deletion and chromosomal translocation of a vast array of gene types, highlighting its importance in leukemia biology. Pathway activation can be therapeutically exploited and may guide new therapies needed for relapsed ALL and other high risk subgroups.

  9. Endocrinological and Cardiological Late Effects Among Survivors of Childhood Acute Lymphoblastic Leukemia

    OpenAIRE

    Hale Ören; Şebnem Yılmaz; Özlem Tüfekçi; Mustafa Kır; Ece Böber; Gülersu İrken; Pakize Karakaya

    2013-01-01

    Objective: Survival rates for childhood acute lymphoblastic leukemia (ALL) have significantly improved and late effects of therapy have been important in the follow-up of survivors. The objective of this study is to identify the endocrinological and cardiological late effects of ALL patients treated in our pediatric hematology unit. Materials and Methods: Patients treated for ALL with BFM protocols after at least 5 years of diagnosis and not relapsed were included in the study. Endocrinologic...

  10. Clinical features and early treatment response of central nervous system involvement in childhood acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Levinsen, Mette; Taskinen, Mervi; Abrahamsson, Jonas

    2014-01-01

    BACKGROUND: Central nervous system (CNS) involvement in childhood acute lymphoblastic leukemia (ALL) remains a therapeutic challenge. PROCEDURE: To explore leukemia characteristics of patients with CNS involvement at ALL diagnosis, we analyzed clinical features and early treatment response of 744...... had higher leukocyte count compared with patients with CNS1 (P symptoms....... Symptoms or clinical findings were present among 27 of 54 patients with CNS3 versus only 7 of 39 patients with CNS2 and 15 of 75 patients with TLP+ (P 

  11. Atherogenic low density lipoprotein phenotype in long-term survivors of childhood acute lymphoblastic leukemia

    OpenAIRE

    Malhotra, Jyoti; Tonorezos, Emily S.; Rozenberg, Marina; Vega, Gloria L.; Sklar, Charles A.; Chou, Joanne; Moskowitz, Chaya S.; Eshelman-Kent, Debra A.; Janiszewski, Peter; Ross, Robert; Oeffinger, Kevin C.

    2012-01-01

    Survivors of childhood acute lymphoblastic leukemia (ALL) have an increased risk of cardiovascular disease. Small density lipoproteins are atherogenic but have not been studied in this population. We conducted a cross-sectional analysis of 110 ALL survivors (mean age, 24.3 years) to determine prevalence of small dense LDL (pattern B) phenotype in ALL survivors and identify associated factors. Lipid subfractions were measured using Vertical Auto Profile-II. Participants with greater than 50% o...

  12. Acute necrotising encephalopathy of childhood after exanthema subitum outside Japan or Taiwan

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    Porto, L.; Lanferman, H.; Moeller-Hartmann, W.; Jacobi, G.; Zanella, F. [Inst. fuer Neuroradiologie, Klinikum der Johann Wolfgang Goethe-Univ., Frankfurt am Main (Germany)

    1999-10-01

    Acute necrotising encephalopathy of childhood (ANE) is an uncommon disease which predominantly affects infants and young children living in Japan and Taiwan. A multifocal encephalopathy with symmetrical lesions in the thalamus, tegmentum of the brain stem, cerebral periventricular white matter and cerebellar medulla is characteristic. We present the imaging features in a 4-year-old Japanese boy who had been living in Germany for 2{sup 1}/{sub 2} years before presentation. (orig.)

  13. Parents' help-seeking behaviours during acute childhood illness at home: A contribution to explanatory theory.

    Science.gov (United States)

    Neill, Sarah J; Jones, Caroline H D; Lakhanpaul, Monica; Roland, Damian T; Thompson, Matthew J

    2016-03-01

    Uncertainty and anxiety surround parents' decisions to seek medical help for an acutely ill child. Consultation rates for children are rising, yet little is known about factors that influence parents' help-seeking behaviours. We used focus groups and interviews to examine how 27 parents of children under five years, from a range of socioeconomic groups in the East Midlands of England, use information to make decisions during acute childhood illness at home. This article reports findings elucidating factors that influence help-seeking behaviours. Parents reported that decision-making during acute childhood illness was influenced by a range of personal, social and health service factors. Principal among these was parents' concern to do the right thing for their child. Their ability to assess the severity of the illness was influenced by knowledge and experience of childhood illness. When parents were unable to access their general practitioner (GP), feared criticism from or had lost trust in their GP, some parents reported using services elsewhere such as Accident and Emergency. These findings contribute to explanatory theory concerning parents' help-seeking behaviours. Professional and political solutions have not reduced demand; therefore, collaborative approaches involving the public and professionals are now needed to improve parents' access to information. © The Author(s) 2014.

  14. Acute childhood diarrhoea in northern Ghana: epidemiological, clinical and microbiological characteristics

    Directory of Open Access Journals (Sweden)

    Danikuu Francis

    2007-09-01

    Full Text Available Abstract Background Acute diarrhoea is a major cause of childhood morbidity and mortality in sub-Saharan Africa. Its microbiological causes and clinico-epidemiological aspects were examined during the dry season 2005/6 in Tamale, urban northern Ghana. Methods Stool specimens of 243 children with acute diarrhoea and of 124 control children were collected. Patients were clinically examined, and malaria and anaemia were assessed. Rota-, astro-, noro- and adenoviruses were identified by (RT- PCR assays. Intestinal parasites were diagnosed by microscopy, stool antigen assays and PCR, and bacteria by culturing methods. Results Watery stools, fever, weakness, and sunken eyes were the most common symptoms in patients (mean age, 10 months. Malaria occurred in 15% and anaemia in 91%; underweight (22% and wasting (19% were frequent. Intestinal micro-organisms were isolated from 77% of patients and 53% of controls (P P = 0.02. Conclusion Rotavirus-infection is the predominant cause of acute childhood diarrhoea in urban northern Ghana. The abundance of putative enteropathogens among controls may indicate prolonged excretion or limited pathogenicity. In this population with a high burden of diarrhoeal and other diseases, sanitation, health education, and rotavirus-vaccination can be expected to have substantial impact on childhood morbidity.

  15. Genomic signatures characterize leukocyte infiltration in myositis muscles

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    Zhu Wei

    2012-11-01

    Full Text Available Abstract Background Leukocyte infiltration plays an important role in the pathogenesis and progression of myositis, and is highly associated with disease severity. Currently, there is a lack of: efficacious therapies for myositis; understanding of the molecular features important for disease pathogenesis; and potential molecular biomarkers for characterizing inflammatory myopathies to aid in clinical development. Methods In this study, we developed a simple model and predicted that 1 leukocyte-specific transcripts (including both protein-coding transcripts and microRNAs should be coherently overexpressed in myositis muscle and 2 the level of over-expression of these transcripts should be correlated with leukocyte infiltration. We applied this model to assess immune cell infiltration in myositis by examining mRNA and microRNA (miRNA expression profiles in muscle biopsies from 31 myositis patients and 5 normal controls. Results Several gene signatures, including a leukocyte index, type 1 interferon (IFN, MHC class I, and immunoglobulin signature, were developed to characterize myositis patients at the molecular level. The leukocyte index, consisting of genes predominantly associated with immune function, displayed strong concordance with pathological assessment of immune cell infiltration. This leukocyte index was subsequently utilized to differentiate transcriptional changes due to leukocyte infiltration from other alterations in myositis muscle. Results from this differentiation revealed biologically relevant differences in the relationship between the type 1 IFN pathway, miR-146a, and leukocyte infiltration within various myositis subtypes. Conclusions Results indicate that a likely interaction between miR-146a expression and the type 1 IFN pathway is confounded by the level of leukocyte infiltration into muscle tissue. Although the role of miR-146a in myositis remains uncertain, our results highlight the potential benefit of deconvoluting the

  16. Genomic signatures characterize leukocyte infiltration in myositis muscles.

    Science.gov (United States)

    Zhu, Wei; Streicher, Katie; Shen, Nan; Higgs, Brandon W; Morehouse, Chris; Greenlees, Lydia; Amato, Anthony A; Ranade, Koustubh; Richman, Laura; Fiorentino, David; Jallal, Bahija; Greenberg, Steven A; Yao, Yihong

    2012-11-21

    Leukocyte infiltration plays an important role in the pathogenesis and progression of myositis, and is highly associated with disease severity. Currently, there is a lack of: efficacious therapies for myositis; understanding of the molecular features important for disease pathogenesis; and potential molecular biomarkers for characterizing inflammatory myopathies to aid in clinical development. In this study, we developed a simple model and predicted that 1) leukocyte-specific transcripts (including both protein-coding transcripts and microRNAs) should be coherently overexpressed in myositis muscle and 2) the level of over-expression of these transcripts should be correlated with leukocyte infiltration. We applied this model to assess immune cell infiltration in myositis by examining mRNA and microRNA (miRNA) expression profiles in muscle biopsies from 31 myositis patients and 5 normal controls. Several gene signatures, including a leukocyte index, type 1 interferon (IFN), MHC class I, and immunoglobulin signature, were developed to characterize myositis patients at the molecular level. The leukocyte index, consisting of genes predominantly associated with immune function, displayed strong concordance with pathological assessment of immune cell infiltration. This leukocyte index was subsequently utilized to differentiate transcriptional changes due to leukocyte infiltration from other alterations in myositis muscle. Results from this differentiation revealed biologically relevant differences in the relationship between the type 1 IFN pathway, miR-146a, and leukocyte infiltration within various myositis subtypes. Results indicate that a likely interaction between miR-146a expression and the type 1 IFN pathway is confounded by the level of leukocyte infiltration into muscle tissue. Although the role of miR-146a in myositis remains uncertain, our results highlight the potential benefit of deconvoluting the source of transcriptional changes in myositis muscle or other

  17. Air pollutants, genes and early childhood acute bronchitis.

    Science.gov (United States)

    Ghosh, Rakesh; Topinka, Jan; Joad, Jesse P; Dostal, Miroslav; Sram, Radim J; Hertz-Picciotto, Irva

    2013-09-01

    Studies have reported gene-by-environment interaction for chronic respiratory conditions but none on acute illnesses in children. We investigated, longitudinally, whether genotype modifies the relationship of environmental exposures (second-hand tobacco smoke, polycyclic aromatic hydrocarbons, particulate matter acute bronchitis in children below two years. A random sample of 1133 children, born between 1994 and 1998, in two districts of the Czech Republic, was followed-up from birth, of which 793 were genotyped. Pediatric records were abstracted for respiratory illnesses. Second-hand tobacco smoke exposure from household members was obtained through questionnaires and verified using urine cotinine. Air monitoring provided estimates of ambient polycyclic aromatic hydrocarbons and PM2.5. Additionally, we collected information on a range of potential confounders including breastfeeding history, indoor fuel use, other children in household, maternal characteristics, ambient temperature etc. DNA was extracted from tissues taken from the middle of the placenta, opposite the umbilical cord. We examined six single nucleotide polymorphisms (GSTM1, GSTP1, GSTT1, CYP1A1 MspI, EPHX1 exon 3 and 4) and one (EPHX1) diplotype. To investigate effect measure modification we constructed logistic regression models using generalized estimating equations (for repeated observations) stratified by genotypes. The EPHX1 low activity diplotype consistently imparts greater susceptibility to bronchitis from second-hand tobacco smoke, polyclic aromatic hydrocarbons (PAH) and PM2.5. Each of these three classes of exposure also showed elevated risk for bronchitis in the presence of either one or two histidines at exon 3 and exon 4 of EPHX1. Additional effect modifiers include CYP1A1 and GSTT1. Several xenobiotic metabolizing genes may modify the impact of second-hand tobacco smoke and ambient air pollutants, polycyclic aromatic hydrocarbons and PM2.5, on acute bronchitis in preschool children

  18. Paternal Smoking and Risk of Childhood Acute Lymphoblastic Leukemia: Systematic Review and Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Ruiling Liu

    2011-01-01

    Full Text Available Objective. To investigate the association between paternal smoking and childhood acute lymphoblastic leukemia (ALL. Method. We identified 18 published epidemiologic studies that reported data on both paternal smoking and childhood ALL risk. We performed a meta-analysis and analyzed dose-response relationships on ALL risk for smoking during preconception, during pregnancy, after birth, and ever smoking. Results. The summary odds ratio (OR of childhood ALL associated with paternal smoking was 1.11 (95% Confidence Interval (CI: 1.05–1.18, I2=18% during any time period, 1.25 (95% CI: 1.08–1.46, I2=53% preconception; 1.24 (95% CI: 1.07–1.43, I2=54% during pregnancy, and 1.24 (95% CI: 0.96–1.60, I2=64% after birth, with a dose-response relationship between childhood ALL and paternal smoking preconception or after birth. Conclusion. The evidence supports a positive association between childhood ALL and paternal ever smoking and at each exposure time period examined. Future epidemiologic studies should assess paternal smoking during well-defined exposure windows and should include biomarkers to assess smoking exposure and toxicological mechanisms.

  19. Cytogenetic Instability in Childhood Acute Lymphoblastic Leukemia Survivors

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    María Sol Brassesco

    2011-01-01

    Full Text Available Contemporary anticancer therapies have largely improved the outcome for children with cancer, especially for Acute Lymphoblastic Leukemia (ALL. Actually, between 78% and 85% of patients achieve complete remission and are alive after 5 years of therapy completion. However, as cure rates increase, new concerns about the late effects of genotoxic treatment emerge, being the risk of developing secondary neoplasias, the most serious life-threatening rising problem. In the present paper, we describe and review the cytogenetic findings in peripheral lymphocytes from ALL survivors, and discuss aspects associated to the occurrence of increased chromosome rearrangements in this growing cohort.

  20. Home paint exposures and risk of childhood acute lymphoblastic leukemia: findings from the Childhood Leukemia International Consortium.

    Science.gov (United States)

    Bailey, Helen D; Metayer, Catherine; Milne, Elizabeth; Petridou, Eleni Th; Infante-Rivard, Claire; Spector, Logan G; Clavel, Jacqueline; Dockerty, John D; Zhang, Luoping; Armstrong, Bruce K; Rudant, Jérémie; Fritschi, Lin; Amigou, Alicia; Hatzipantelis, Emmanuel; Kang, Alice Y; Stiakaki, Eftichia; Schüz, Joachim

    2015-09-01

    It has been suggested that home paint exposure increases the risk of childhood acute lymphoblastic leukemia (ALL). We obtained individual level data from eight case-control studies participating in the Childhood Leukemia International Consortium. All studies had home paint exposure data (sometimes including lacquers and varnishes) for the pregnancy period with additional data for the 1-3-month period before conception in five, the year before conception in two, and the period after birth in four studies, respectively. Cytogenetic subtype data were available for some studies. Data were harmonized to a compatible format. Pooled analyses of individual data were undertaken using unconditional logistic regression. Based on 3,002 cases and 3,836 controls, the pooled odds ratio (OR) for home paint exposure in the 1-3 months before conception and risk of ALL was 1.54 [95% confidence interval (CI) 1.28, 1.85], while based on 1,160 cases and 1,641 controls for exposure in the year before conception, it was 1.00 (95% CI 0.86, 1.17). For exposure during pregnancy, using 4,382 cases and 5,747 controls, the pooled OR was 1.14 (95% CI 1.04, 1.25), and for exposure after birth, the OR was 1.22 (95% CI 1.07, 1.39), based on data from 1,962 cases and 2,973 controls. The risk was greater for certain cytogenetic subtypes and if someone other than the parents did the painting. Home paint exposure shortly before conception, during pregnancy, and/or after birth appeared to increase the risk of childhood ALL. It may be prudent to limit exposure during these periods.

  1. Recent trauma and acute infection as risk factors for childhood arterial ischemic stroke.

    Science.gov (United States)

    Hills, Nancy K; Johnston, S Claiborne; Sidney, Stephen; Zielinski, Brandon A; Fullerton, Heather J

    2012-12-01

    Trauma and acute infection have been associated with stroke in adults, and are prevalent exposures in children. We hypothesized that these environmental factors are independently associated with childhood arterial ischemic stroke (AIS). In a case-control study nested within a cohort of 2.5 million children (≤19 years old) enrolled in an integrated health care plan (1993-2007), childhood AIS cases (n = 126) were identified from electronic records and confirmed through chart review. Age- and facility-matched controls (n = 378) were randomly selected from the cohort. Exposures were determined from review of medical records prior to the stroke diagnosis, or the same date for the paired controls; time windows were defined a priori. A medical encounter for head or neck trauma within the prior 12 weeks was an independent risk factor for childhood AIS (odds ratio [OR], 7.5; 95% confidence interval [CI], 2.9-19.3), present in 12% of cases (1.6% of controls). Median time from trauma to stroke was 0.5 days (interquartile range, 0-2 days); post hoc redefinition of trauma exposure (prior 1 week) was more strongly associated with AIS: OR, 39; 95% CI, 5.1-298. A medical encounter for a minor acute infection (prior 4 weeks) was also an independent risk factor (OR, 4.6; 95% CI, 2.6-8.2), present in 33% of cases (13% of controls). No single infection type predominated. Only 2 cases had exposure to trauma and infection. Trauma and acute infection are common independent risk factors for childhood AIS, and may be targets for stroke prevention strategies. Copyright © 2012 American Neurological Association.

  2. Oral rehydration salts, zinc supplement and rota virus vaccine in the management of childhood acute diarrhea

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    Abdulwahab MA Telmesani

    2010-01-01

    Full Text Available Acute diarrhea remains a major cause of morbidity and mortality in children. Since the introduction of oral rehydration salts (ORS mortality has dropped to less than 50% worldwide. Low osmolarity ORS improved the outcome and reduced the hospitalization further. Zinc difficiency has been found to be associated with severe episodes of acute diarrhea. Zinc supplement in developing countries did reduce the incidence and prevalence of diarrhea. In addition, Zinc supplement significantly reduced the severity of diarrhea and duration of the episode. In the Americas and Europe, Rota virus vaccine was 90% effective in preventing severe episodes of severe rotavirus gastroenteritis. This review concludes that low osmolarilty ORS, zinc supplementation and rotavirus vaccine are major factors in reducing the morbidity, mortality and hospitalization resulting from to acute gastroenteritis in childhood.

  3. Oral rehydration salts, zinc supplement and rota virus vaccine in the management of childhood acute diarrhea.

    Science.gov (United States)

    Telmesani, Abdulwahab Ma

    2010-05-01

    Acute diarrhea remains a major cause of morbidity and mortality in children. Since the introduction of oral rehydration salts (ORS) mortality has dropped to less than 50% worldwide. Low osmolarity ORS improved the outcome and reduced the hospitalization further. Zinc difficiency has been found to be associated with severe episodes of acute diarrhea. Zinc supplement in developing countries did reduce the incidence and prevalence of diarrhea. In addition, Zinc supplement significantly reduced the severity of diarrhea and duration of the episode. In the Americas and Europe, Rota virus vaccine was 90% effective in preventing severe episodes of severe rotavirus gastroenteritis. This review concludes that low osmolarilty ORS, zinc supplementation and rotavirus vaccine are major factors in reducing the morbidity, mortality and hospitalization resulting from to acute gastroenteritis in childhood.

  4. Childhood Blastic Plasmacytoid Dendritic Cell Neoplasm Mimicking Acute Rheumatic Fever: Report of an Unusual Clinical Presentation and Review of Literature.

    Science.gov (United States)

    Rajkumari, Banashree Devi; Munikoty, Vinay; Sreedharanunni, Sreejesh; Jain, Richa; Sachdeva, Man Updesh Singh; Varma, Neelam

    2017-08-30

    Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is very rarely diagnosed in children with less than 50 cases in the literature. We report a case of childhood BPDCN who mimicked acute rheumatic fever at presentation. Majority of the reported childhood BPDCN received acute lymphoblastic leukemia-like chemotherapy with/without stem cell therapy, whereas those who received acute myeloid leukemia-like therapy predominantly succumbed to disease or sepsis. Overall 68% of the patients were alive and achieved complete remission with an overall prognosis slightly better in children compared with adults. The case is reported due to its unique unusual clinical presentation and its rarity in pediatric population.

  5. Coagulation profile during induction chemotherapy in childhood acute lymphoblastic leukemia.

    Science.gov (United States)

    Sehgal, Shivali; Sharma, Sunita; Chandra, Jagdish; Nangia, Anita

    2017-01-01

    Thromboembolism in children with acute lymphoblastic leukemia (ALL) is most commonly reported after the initiation of antileukemic therapy, indicating a possible interaction of disease and therapy. To study the effect of induction chemotherapy on coagulation parameters in pediatric ALL patients. Thirty-seven newly diagnosed patients of ALL up to 18 years of age were evaluated along with 30 age- and sex-matched controls. At the time of diagnosis (day 0), various coagulation parameters were tested. These were sequentially analyzed on day 14 (after the completion of L-asparaginase doses) and on day 28 of therapy (after the completion of induction). Prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen, protein C (PC) activity, and protein S (PS) activity were done by a clot-based method. Antithrombin (AT) assay was performed by chromogenic method. D-dimer (D-DI), tissue plasminogen activator (tPA), and plasminogen activator inhibitor type 1 (PAI-1) levels were assayed by ELISA method. The statistical analysis was done using Statistical Package for Social Sciences version 17.0. No major change in PT and APTT was observed during chemotherapy; however, fibrinogen levels declined significantly (P = 0.04), following L-asparaginase treatment. D-DI levels were significantly raised at diagnosis (P chemotherapy cause thrombin activation, decrease in natural inhibitors, and hypofibrinolysis, resulting in hypercoagulability. Thus, ALL per se is a hypercoagulable state and the prothrombotic condition at the time of diagnosis gets enhanced during induction chemotherapy.

  6. The clinical significance of lung hypoexpansion in acute childhood asthma

    Energy Technology Data Exchange (ETDEWEB)

    Spottswood, Stephanie E. [Department of Radiology, Medical College of Virginia, Virginia Commonwealth University Health System, Box 980615, 23298-0615, Richmond, VA (United States); Department of Radiology, The Children' s Hospital of the King' s Daughters, 601 Children' s Lane, Norfolk, VA 23507 (United States); Allison, Kelley Z.; Narla, Lakshmana D.; Lowry, Patricia A. [Department of Radiology, Medical College of Virginia, Virginia Commonwealth University Health System, Box 980615, 23298-0615, Richmond, VA (United States); Lopatina, Olga A.; Sethi, Narinder N. [School of Medicine, Medical College of Virginia, Virginia Commonwealth University Health System, Richmond, VA (United States); Nettleman, Mary D. [Department of Internal Medicine, B-427 Clinical Center, Michigan State University, East Lansing, MI 48824 (United States)

    2004-04-01

    Many children experiencing acute asthmatic episodes have chest radiographs, which may show lung hyperinflation, hypoinflation, or normal inflation. Lung hypoinflation may be a sign of respiratory fatigue and poor prognosis. To compare the clinical course in children with asthma according to the degree of lung inflation on chest radiographs. We conducted a retrospective study during a 24-month period (from July 1999 to July 2001) of children aged 0-17 years, who presented to a pediatric emergency department or outpatient clinic with an asthma exacerbation. Chest radiographs obtained at presentation were reviewed independently by three pediatric radiologists who were blinded to the admission status of the patient. The correlation between hypoinflation and hospital admission was assessed in three age groups: 0-2 years, 3-5 years, and 6-17 years. Hypoinflation on chest radiographs was significantly correlated with hospital admission for children aged 6-17 years (odds ratio 16.00, 95% confidence interval 1.89-135.43). The inter-reader agreement for interpretation of these radiographs was strong, with a kappa score of 0.76. Hypoinflation was not correlated with admission in younger children. Lung hypoinflation is associated with a greater likelihood of hospital admission in children aged 6 years or older. Therefore, hypoinflation was a poor prognostic sign and may warrant more aggressive therapy. (orig.)

  7. Monosomal karyotype is not a predictor of dismal outcome in childhood de novo acute myeloid leukemia.

    Science.gov (United States)

    Lee, Na Hee; Choi, Young Bae; Yi, Eun-Sang; Lee, Soo Hyun; Kim, Hee-Jin; Lee, Ji Won; Sung, Ki Woong; Koo, Hong Hoe; Yoo, Keon Hee

    2016-11-01

    Monosomal karyotype (MK) is known as a far end of the unfavorable cytogenetics in adult acute myeloid leukemia (AML), while available data in childhood AML is scarce. In this study, we investigated the prevalence and prognostic value of MK with retrospectively analyzed 119 patients newly diagnosed with childhood de novo AML. Ten patients (8.4%) revealed to have MK. All MK-positive (MK(+)) AML were associated with complex cytogenetic abnormalities and belonged to the cytogenetic adverse-risk group. Nine of MK(+) patients (90%) achieved complete remission. The event-free survival (EFS) and overall survival (OS) of MK(+) adverse group were comparable to the ESF and OS of MK-negative non-adverse group (EFS 60.0±15.5% vs 59.0±5.1%, P=0.925; OS 70.0±14.5% vs 58.1±5.3%, P=0.696). In multivariate analysis, MK was not an independent adverse prognostic factor for EFS (hazard ratio 0.45, 95% C.I. 0.13-1.50, P=0.194). In addition, 7 of 9 MK(+) patients who received allogeneic hematopoietic stem cell transplantation (HSCT) survived event-free, with a median follow-up of 64 months. In conclusion, MK did not act as an adverse prognostic factor in childhood de novo AML. Allogeneic HSCT might have contributed to the excellent outcome of MK(+) childhood de novo AML. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Quantitative assessments of indoor air pollution and the risk of childhood acute leukemia in Shanghai.

    Science.gov (United States)

    Gao, Yu; Zhang, Yan; Kamijima, Michihiro; Sakai, Kiyoshi; Khalequzzaman, Md; Nakajima, Tamie; Shi, Rong; Wang, Xiaojin; Chen, Didi; Ji, Xiaofan; Han, Kaiyi; Tian, Ying

    2014-04-01

    We investigated the association between indoor air pollutants and childhood acute leukemia (AL). A total of 105 newly diagnosed cases and 105 1:1 gender-, age-, and hospital-matched controls were included. Measurements of indoor pollutants (including nitrogen dioxide (NO2) and 17 types of volatile organic compounds (VOCs)) were taken with diffusive samplers for 64 pairs of cases and controls. Higher concentrations of NO2 and almost half of VOCs were observed in the cases than in the controls and were associated with the increased risk of childhood AL. The use of synthetic materials for wall decoration and furniture in bedroom was related to the risk of childhood AL. Renovating the house in the last 5 years, changing furniture in the last 5 years, closing the doors and windows overnight in the winter and/or summer, paternal smoking history and outdoor pollutants affected VOC concentrations. Our results support the association between childhood AL and indoor air pollution. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. PTPRG inhibition by DNA methylation and cooperation with RAS gene activation in childhood acute lymphoblastic leukemia.

    Science.gov (United States)

    Xiao, Jianqiao; Lee, Seung-Tae; Xiao, Yuanyuan; Ma, Xiaomei; Houseman, E Andres; Hsu, Ling-I; Roy, Ritu; Wrensch, Margaret; de Smith, Adam J; Chokkalingam, Anand; Buffler, Patricia; Wiencke, John K; Wiemels, Joseph L

    2014-09-01

    While the cytogenetic and genetic characteristics of childhood acute lymphoblastic leukemias (ALL) are well studied, less clearly understood are the contributing epigenetic mechanisms that influence the leukemia phenotype. Our previous studies and others identified gene mutation (RAS) and DNA methylation (FHIT) to be associated with the most common cytogenetic subgroup of childhood ALL, high hyperdiploidy (having five more chromosomes). We screened DNA methylation profiles, using a genome-wide high-dimension platform of 166 childhood ALLs and 6 normal pre-B cell samples and observed a strong association of DNA methylation status at the PTPRG locus in human samples with levels of PTPRG gene expression as well as with RAS gene mutation status. In the 293 cell line, we found that PTPRG expression induces dephosphorylation of ERK, a downstream RAS target that may be critical for mutant RAS-induced cell growth. In addition, PTPRG expression is upregulated by RAS activation under DNA hypomethylating conditions. An element within the PTPRG promoter is bound by the RAS-responsive transcription factor RREB1, also under hypomethylating conditions. In conclusion, we provide evidence that DNA methylation of the PTPRG gene is a complementary event in oncogenesis induced by RAS mutations. Evidence for additional roles for PTPR family member genes is also suggested. This provides a potential therapeutic target for RAS-related leukemias as well as insight into childhood ALL etiology and pathophysiology. © 2014 UICC.

  10. Childhood central nervous system leukemia: historical perspectives, current therapy, and acute neurological sequelae

    Energy Technology Data Exchange (ETDEWEB)

    Laningham, Fred H. [St. Jude Children' s Research Hospital, Division of Diagnostic Imaging, Department of Radiological Sciences, Memphis, TN (United States); University of Tennessee Health Sciences Center, Memphis, TN (United States); Kun, Larry E. [St. Jude Children' s Research Hospital, Division of Radiation Oncology, Department of Radiological Sciences, Memphis, TN (United States); University of Tennessee Health Sciences Center, Memphis, TN (United States); Reddick, Wilburn E.; Ogg, Robert J. [St. Jude Children' s Research Hospital, Division of Translational Imaging Research, Department of Radiological Sciences, Memphis, TN (United States); Morris, E.B. [St. Jude Children' s Research Hospital, Department of Oncology, Memphis, TN (United States); Pui, Ching-Hon [St. Jude Children' s Research Hospital, Department of Oncology, Memphis, TN (United States); University of Tennessee Health Sciences Center, Memphis, TN (United States)

    2007-11-15

    During the past three decades, improvements in the treatment of childhood leukemia have resulted in high cure rates, particularly for acute lymphoblastic leukemia (ALL). Unfortunately, successful therapy has come with a price, as significant morbidity can result from neurological affects which harm the brain and spinal cord. The expectation and hope is that chemotherapy, as a primary means of CNS therapy, will result in acceptable disease control with less CNS morbidity than has been observed with combinations of chemotherapy and radiotherapy over the past several decades. In this review we discuss the poignant, historical aspects of CNS leukemia therapy, outline current methods of systemic and CNS leukemia therapy, and present imaging findings we have encountered in childhood leukemia patients with a variety of acute neurological conditions. A major objective of our research is to understand the neuroimaging correlates of acute and chronic effects of cancer and therapy. Specific features related to CNS leukemia and associated short-term toxicities, both disease- and therapy-related, are emphasized in this review with the specific neuroimaging findings. Specific CNS findings are similarly important when treating acute myelogenous leukemia (AML), and details of leukemic involvement and toxicities are also presented in this entity. Despite contemporary treatment approaches which favor the use of chemotherapy (including intrathecal therapy) over radiotherapy in the treatment of CNS leukemia, children still occasionally experience morbid neurotoxicity. Standard neuroimaging is sufficient to identify a variety of neurotoxic sequelae in children, and often suggest specific etiologies. Specific neuroimaging findings frequently indicate a need to alter antileukemia therapy. It is important to appreciate that intrathecal and high doses of systemic chemotherapy are not innocuous and are associated with acute, specific, recognizable, and often serious neurological

  11. MASTICATORY MUSCLE MYOSITIS IN A GRAY WOLF (CANIS LUPUS).

    Science.gov (United States)

    Kent, Marc; Glass, Eric N; Castro, Fernando A; Miller, Andrew D; de Lahunta, Alexander

    2017-03-01

    A 10-yr-old male, neutered gray wolf ( Canis lupus ) was presented for atrophy of the temporalis and masseter muscles. Clinical signs and magnetic resonance imaging were consistent with a myopathy. Positive serology for antibody titers directed against Type 2M myofibers, and the observation of a mixed mononuclear inflammatory cell infiltrate along with eosinophils and neutrophils within the temporalis muscle, were diagnostic for masticatory muscle myositis. Importantly, protozoal myositis was excluded based on other clinicopathologic data. The case highlights the potential for immune-mediated polymyositis in canids other than the domesticated dog ( Canis lupus familaris). Additionally, awareness of a diet in which raw meat is used should prompt a thorough investigation for an underlying infectious myositis in the gray wolf.

  12. Myositis with antimitochondrial antibodies diagnosed by rectus abdominis muscle biopsy.

    Science.gov (United States)

    Uenaka, Takeshi; Kowa, Hisatomo; Sekiguchi, Kenji; Nagata, Kakuya; Ohtsuka, Yoshihisa; Kanda, Fumio; Toda, Tatsushi

    2013-05-01

    Antimitochondrial antibodies are autoantibodies detected in 90% of primary biliary cirrhosis (PBC) patients. Some PBC cases are complicated by myositis, which is difficult to confirm due to minimal histological evidence of inflammation in limb muscles. Our aim was to determine the extent of inflammatory changes in a truncal muscle biopsy specimen from a PBC patient. A 48-year-old woman with a 5-year history of atrial fibrillation and chronic heart failure was evaluated for elevated serum creatine kinase level. Antimitochondrial M2 antibodies were detected, and PBC was diagnosed. A biceps brachii biopsy specimen showed mild, non-specific myogenic changes; a second biopsy was performed on the rectus abdominis muscle, which showed typical inflammatory changes. Myositis with antimitochondrial M2 antibodies was confirmed. In myositis patients with antimitochondrial M2 antibodies, muscles of the extremities are involved to a lesser extent. Radiological and histological examination focusing on truncal muscles, including a biopsy, is important. Copyright © 2012 Wiley Periodicals, Inc.

  13. Focal myositis of the thigh: unusual MR pattern

    Energy Technology Data Exchange (ETDEWEB)

    Llauger, Jaume; Palmer, Jaume; San Roman, Luis [Department of Radiology, Hospital de la Santa Creu i Sant Pau, Barcelona (Spain); Bague, Silvia; Matias-Guiu, Xavier [Department of Pathology, Hospital de la Santa Creu i Sant Pau, Barcelona (Spain); Doncel, Antonio [Department of Orthopedic Surgery, Hospital de la Santa Creu i Sant Pau, Barcelona (Spain)

    2002-05-01

    Focal myositis is a commonly referenced, infrequently reported and poorly documented benign inflammatory pseudotumor which may be misdiagnosed clinically as a malignant tumor. We report the clinicopathologic features and magnetic resonance imaging findings in a case of focal myositis in the thigh of a 55-year-old woman. A different radiologic presentation of this disorder is described. The gross appearance of the lesion, previously undescribed, appears to be rather specific for such a pseudoneoplastic disorder, and correlates very well with the magnetic resonance imaging features. (orig.)

  14. Antimitochondrial antibodies-positive myositis accompanied by cardiac involvement.

    Science.gov (United States)

    Yamanaka, Tetsuo; Fukatsu, Toru; Ichinohe, Yoshimaro; Hirata, Yasunobu

    2017-03-31

    We report a 55-year-old man who experienced proximal muscle weakness accompanied by the atrial flutter (AFL) with 1:1 conduction. Detailed examination revealed elevated antimitochondrial antibodies (AMA) and creatine kinase (CK). AFL was converted to sinus rhythm by cardioversion. He was diagnosed as AMA-positive myositis-associated AFL and was treated by prednisolone. Although his muscle weakness and CK level improved, AFL with 1:1 conduction reappeared. Therefore, radiofrequency catheter ablation (RFCA) was needed to treat the AFL, resulting in maintenance of sinus rhythm. This case report describes cardiac involvement in a patient with AMA-positive myositis. 2017 BMJ Publishing Group Ltd.

  15. Comparison of MRI and renal cortical scintigraphy findings in childhood acute pyelonephritis: preliminary experience

    Energy Technology Data Exchange (ETDEWEB)

    Kovanlikaya, Arzu; Okkay, Nese; Cakmakci, Handan E-mail: cakmakh@egenet.com.tr; Oezdogan, Oezhan; Degirmenci, Berna; Kavukcu, Salih

    2004-01-01

    Objective: The diagnosis of acute pyelonephritis in children remains a clinical challenge. It may cause permanent renal scar formation and results in the chronic renal failure if prompt diagnosis and treatment are delayed. The purpose of this study is to compare magnetic resonance imaging (MRI) and renal cortical scintigraphy (RCS) findings in childhood acute pyelonephritis and to determine pyelonephritic foci in the acute phase. Materials and method: Twenty children (15 females and five males) with symptoms dysuria, enuresis, costovertebral pain, fever of 37.5 degree sign C or more and/or positive urine culture were imaged by unenhanced turbo spin echo T2, spin echo T1-weighted, pre- and post-gadolinium inversion recovery MRI and RCS. Both imaging techniques were read independently by two radiologists and nuclear medicine specialists. Sensitivity and specificity of MRI in detecting acute pyelonephritic foci and scar lesions were calculated. Furthermore, in order to calculate the reliability of MRI over RCS in differentiating scar tissue and acute pyelonephritic foci, follow-up MRI studies were done in six patients after treatment of acute pyelonephritis. Results: Sensitivity and specificity of MRI in the detection of pyelonephritic lesions were found to be 90.9 and 88.8%, respectively. There is no statistically significant difference in lesion detection between the two diagnostic modalities (P>0.05). Conclusion: Post-gadolinium MR images show significant correlation with RCS in the determination of renal pathology. Moreover, the ability of discriminating acute pyelonephritic foci and renal scar in early stages of disease is the superiority of MRI.

  16. Primary segmental omental infarction as a rare cause of acute abdominal pain in childhood

    Directory of Open Access Journals (Sweden)

    N.F. Tepeneu

    2018-01-01

    Full Text Available Introduction: Primary omental infarction (POI has a low incidence worldwide, with most cases occurring in adults. This condition is rarely considered in the differential diagnosis of acute abdominal pain in childhood. Material and methods: We present 2 cases of omental infarction in an obese 8-year-old boy and a 5-year-old boy who presented with acute abdominal pain in the right abdomen. Both patients were initially treated with intravenous fluids and analgesics with no improvement. Abdominal ultrasound of the first patient showed free intraperitoneal fluid, meteorism and distended bowel loops. The appendix was not visualized. With a presumptive clinical diagnosis of appendicitis the child underwent laparotomy.On entering the peritoneal cavity an omental infarction was seen and a portion of the omentum was resected. Appendectomy was performed.The second patient presented with acute abdominal pain in the right upper quadrant, which started 2 days before. There was a history of possible abdominal trauma about 3 weeks earlier. The patient had repeated ultrasound examinations and a CT scan of the abdomen which showed a omental infarction. He underwent laparoscopy and resection of the omental infarction, as well as incidental appendectomy. Results: The postoperative period was uneventful. The first patient was discharged on day 3, the second patient on day 4 after surgery. Histology showed a normal vermiform appendix and an omental infarction in both cases. Conclusion and discussion: Since the omental infarction as etiology of acute abdominal pain is uncommon in children, we emphasize the importance of accurate diagnosis and appropriate treatment of omental infarction. Keywords: Primary segmental omental infarction (POI, Appendicitis, Childhood

  17. GSTM1 and GSTT1 null polymorphisms and childhood acute leukemia risk: evidence from 26 case-control studies.

    Directory of Open Access Journals (Sweden)

    Qiuqin Tang

    Full Text Available Several molecular epidemiological studies have been conducted to examine the association between glutathione S-transferase mu-1 (GSTM1 and glutathione S-transferase theta-1 (GSTT1 null polymorphisms and childhood acute leukemia; however, the conclusions remain controversial. We performed an extensive meta-analysis on 26 published case-control studies with a total of 3252 cases and 5024 controls. Crude odds ratios (ORs with 95% confidence interval were used to assess the strength of association between childhood acute leukemia risk and polymorphisms of GSTM1 and GSTT1. With respect to GSTM1 polymorphism, significantly increased risk of childhood acute leukemia was observed in the overall analysis (OR = 1.30; 95%CI, 1.11-1.51. Furthermore, a stratification analysis showed that the risk of GSTM1 polymorphism are associated with childhood acute leukemia in group of Asians (OR = 1.94; 95%CI, 1.53-2.46, Blacks (OR = 1.76; 95%CI, 1.07-2.91, ALL (OR = 1.33; 95%CI, 1.13-1.58, '< 100 cases and <100 controls' (OR = 1.79; 95%CI, 1.21-2.64, '≥ 100 cases and ≥ 100 controls' (OR = 1.25; 95%CI, 1.02-1.52, and population-based control source (OR = 1.40; 95%CI, 1.15-1.69. With respect to GSTT1 polymorphism, significant association with childhood acute leukemia risk was only found in subgroup of Asian. This meta-analysis supports that GSTM1 null polymorphism is capable of causing childhood acute leukemia susceptibility.

  18. Association of the methylenetetrahydrofolate reductase polymorphism in Korean patients with childhood acute lymphoblastic leukemia.

    Science.gov (United States)

    Kim, Nam Keun; Chong, So Young; Jang, Moon Ju; Hong, Seung Ho; Kim, Heung Sik; Cho, Eun Kyung; Lee, Jung Ae; Ahn, Myung Ju; Kim, Chul Soo; Oh, Doyeun

    2006-01-01

    Methylenetetrahydrofolate reductase plays a central role in converting folate to methyl donor for DNA methylation. Recently, methylenetetrahydrofolate reductase (MTHFR C677T and A1298C) mutations were discovered to be associated with childhood acute lymphoblastic leukemia (ALL), as well as colon cancer, lymphoma, esophageal and stomach cancer. Therefore, it was hypothesized that the MTHFR polymorphisms are associated with the risk of childhood ALL in the Korean population. DNA samples taken from 66 patients with ALL and 100 age-matched controls were analyzed using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay for detection of MTHFR C677T and A1298C mutations. The frequency of the AC genotype for MTHFR A1298C polymorphism was significantly different between the controls and the cases (OR, 2.22; CI, 95% 1.09-4.51, p=0.03). The 1298AC+CC genotype was also significantly different (OR, 2.11; 95% CI, 1.06-4.22; p=0.049). There was, however, no significant difference for MTHFR C677T polymorphism and combined genotype frequencies between the two groups. Although no consistent results on associations between MTHFR A 1298C polymorphism and ALL in the populations studied were obtained, the A1298C polymorphism, at least in Koreans, may be a genetic determinant among childhood ALL patients.

  19. The frequency of NPM1 mutations in childhood acute myeloid leukemia

    Directory of Open Access Journals (Sweden)

    Karamolegou Kalliopi

    2010-10-01

    Full Text Available Abstract Background Mutations in the nucleophosmin (NPM1 gene have been solely associated with childhood acute myeloid leukemia (AML. We evaluated the frequency of NPM1 mutations in childhood AML, their relation to clinical and cytogenetic features and the presence of common FLT3 and RAS mutations. Results NPM1 mutations were found in 8% of cases. They involved the typical type 'A' mutation and one novel mutation characterized by two individual base pair substitutions, which resulted in 2 amino acid changes (W290 and (S293 in the NPM protein. FLT3/ITD mutations were observed in 12% of the cases and in one NPM1-mutated case bearing also t(8;21 (q22;q22. No common RAS mutations were identified. Conclusions A relatively consistent NPM1 mutation rate was observed, but with variations in types of mutations. The role of different types of NPM1 mutations, either individually or in the presence of other common gene mutations may be essential for childhood AML prognosis.

  20. Using adaptive model predictive control to customize maintenance therapy chemotherapeutic dosing for childhood acute lymphoblastic leukemia.

    Science.gov (United States)

    Noble, Sarah L; Sherer, Eric; Hannemann, Robert E; Ramkrishna, Doraiswami; Vik, Terry; Rundell, Ann E

    2010-06-07

    Acute lymphoblastic leukemia (ALL) is a common childhood cancer in which nearly one-quarter of patients experience a disease relapse. However, it has been shown that individualizing therapy for childhood ALL patients by adjusting doses based on the blood concentration of active drug metabolite could significantly improve treatment outcome. An adaptive model predictive control (MPC) strategy is presented in which maintenance therapy for childhood ALL is personalized using routine patient measurements of red blood cell mean corpuscular volume as a surrogate for the active drug metabolite concentration. A clinically relevant mathematical model is developed and used to describe the patient response to the chemotherapeutic drug 6-mercaptopurine, with some model parameters being patient-specific. During the course of treatment, the patient-specific parameters are adaptively identified using recurrent complete blood count measurements, which sufficiently constrain the patient parameter uncertainty to support customized adjustments of the drug dose. While this work represents only a first step toward a quantitative tool for clinical use, the simulated treatment results indicate that the proposed mathematical model and adaptive MPC approach could serve as valuable resources to the oncologist toward creating a personalized treatment strategy that is both safe and effective. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

  1. Risk factors for treatment related mortality in childhood acute lymphoblastic leukaemia

    DEFF Research Database (Denmark)

    Lund, Bendik; Åsberg, Ann; Heyman, Mats

    2011-01-01

    BACKGROUND: In spite of major improvements in the cure rate of childhood acute lymphoblastic leukaemia (ALL), 2-4% of patients still die from treatment related complications. PROCEDURE: We investigated the pattern of treatment related deaths (TRDs) and possible risk factors in the NOPHO ALL-92 an...... towards patients at risk. Pediatr Blood Cancer. © 2010 Wiley-Liss, Inc.......BACKGROUND: In spite of major improvements in the cure rate of childhood acute lymphoblastic leukaemia (ALL), 2-4% of patients still die from treatment related complications. PROCEDURE: We investigated the pattern of treatment related deaths (TRDs) and possible risk factors in the NOPHO ALL-92...... and ALL-2000 protocols. Fifty-five TRDs were identified among the 1,645 ALL-92 patients and 33 among the 1,090 ALL-2000 patients. RESULTS: There was no significant difference in the incidence of TRDs between the two protocols (3.4% vs. 3.2%). Five patients died before initiation of therapy (0...

  2. [Effects of birth order, maternal abortion and mode of delivery on childhood acute leukemia risk: a meta-analysis].

    Science.gov (United States)

    Zou, Guobin; Sha, Xia

    2014-03-01

    To evaluate the associations between birth order, maternal abortion and mode of delivery and childhood acute leukemia risk. Multiple electronic databases were searched to identify relevant studies up to March 2013 using the search terms "childhood leukemia", "acute lymphoblastic leukemia", "acute myeloid leukemia","birth order", "abortion", "miscarriage", "cesarean", "birth characteristics" and "prenatal risk factor". Data from cohort and case-control studies were analyzed using the Stata software. Twenty-three studies were included in this meta-analysis according to the selection criteria. No significant associations were identified for birth order and mode of delivery (birth order = 2: OR = 0.97, 95%CI: 0.89-1.05; birth order = 3: OR = 1.00, 95%CI: 0.91-1.11; birth order ≥ 4: OR = 1.02, 95%CI: 0.87-1.20; mode of delivery: OR = 1.05, 95%CI: 0.96-1.15). However, there was a significant association between maternal abortion and childhood acute leukemia risk (spontaneous abortion: OR = 1.21, 95%CI: 1.05-1.41; induced abortion: OR = 1.23, 95%CI: 1.07-1.43). Furthermore, the stratified analysis by disease subtypes showed that spontaneous and induced abortions were significantly associated with the risks of childhood acute myeloid leukemia (OR = 1.71, 95%CI: 1.09-2.70) and acute lymphoblastic leukemia (OR = 1.23, 95%CI: 1.05-1.42), respectively. This meta-analysis revealed that maternal abortion might contribute to the childhood acute leukemia risk.

  3. Case Report - Myositis Ossificans: Two Case Presentations | Lungu ...

    African Journals Online (AJOL)

    Myositis Ossificans [MO], a florid ossification, may occur in muscles and soft tissue. It is also called by many different names. The lesion contains actively proliferating fibroblasts and osteoblasts and early in its development may be confused with a malignant tumor. It commonly affects vigorous young men and more so ...

  4. Myositis ossificans progressive: case report | Talbi | Pan African ...

    African Journals Online (AJOL)

    Myositis ossificansprogressiva (MOP) is an autosomal dominant disorder. There is a progressive ectopic ossification and skeletal malformation, mainly in the connective tissue of muscle. The diagnosis is based on the clinical findings and radiological demonstration of the skeletal malformations. A 38-year-old female patient ...

  5. Extraocular myositis in a female puppy | Adegboye | Open ...

    African Journals Online (AJOL)

    Extraocular myositis (EOM) is not commonly encountered in dogs. It is generally diagnosed based on clinical features of exophthalmos without third eyelid protrusion, pain or vision loss. The traditional treatment of choice is prednisolone. This report describes a case of a mixed-breed puppy with clinical signs consistent with ...

  6. Oval pulsed high-dose dexamethasone for myositis

    NARCIS (Netherlands)

    Hoogendijk, JE; Wokke, JHJ; de Visser, M

    To study the short-term effect of oral pulsed high-dose dexamethasone for myositis we treated eight newly diagnosed patients with three 28-day cycles of oral dexamethasone. Primary outcome measures were muscle strength, pain, and serum creatine kinase activity. Sis patients responded. Side effects

  7. Oral pulsed high-dose dexamethasone for myositis

    NARCIS (Netherlands)

    van der Meulen, M. F.; Hoogendijk, J. E.; Wokke, J. H.; de Visser, M.

    2000-01-01

    To study the short-term effect of oral pulsed high-dose dexamethasone for myositis we treated eight newly diagnosed patients with three 28-day cycles of oral dexamethasone. Primary outcome measures were muscle strength, pain, and serum creatine kinase activity. Six patients responded. Side effects

  8. Brucellosis presenting as piriformis myositis: a case report

    Directory of Open Access Journals (Sweden)

    Romanos Odysseas

    2011-03-01

    Full Text Available Abstract Introduction Myositis is a rare bacterial muscle infection. Involvement of the piriformis muscle has been rarely reported in the literature. In this report we describe a case of piriformis myositis due to Brucella melitensis, which to the best of our knowledge is the first such case presented in the literature. Case presentation We report the case of a 19-year-old Caucasian man who presented to our institution with fever and right hip pain. Brucellosis was suspected, but the clinical suspicion was for spondylodiscitis. A pelvic magnetic resonance imaging scan allowed prompt diagnosis of inflammatory involvement of the right piriformis muscle. Blood culture results were positive for B. melitensis. Our patient was treated with antibiotics, and follow-up magnetic resonance imaging scans showed resolution of the inflammation. Conclusion Brucellosis can present as piriformis myositis. The clinical diagnosis of piriformis myositis is difficult, as it can mimic other common entities such as referred back pain from spondylodiscitis. Magnetic resonance imaging is the method of choice for establishing the diagnosis in the early stages of the disease, as late diagnosis can lead to abscess formation and the need for drainage.

  9. Recovery from severe dysphagia in systemic sclerosis - myositis ...

    African Journals Online (AJOL)

    Recovery from severe dysphagia in systemic sclerosis - myositis overlap: a case report. Keith J Chinniah, Girish M Mody. Department of Rheumatology, School of Clinical Medicine, College of Health Sciences,. University of KwaZulu-Natal and Inkosi Albert Luthuli Central Hospital, Durban, South Africa. Abstract.

  10. Recovery from severe dysphagia in systemic sclerosis - myositis ...

    African Journals Online (AJOL)

    Clinical case: A 56-year old African Black woman initially presented with systemic sclerosis (SSC) - myositis overlap and interstitial lung disease. She responded to high dose corticosteroids and cyclophosphamide followed by azathioprine, with improvement in her lung function and regression of the skin changes. Six years ...

  11. Long-Term Neuropsychological Outcomes of Childhood Onset Acute Disseminated Encephalomyelitis (ADEM): a Meta-Analysis.

    Science.gov (United States)

    Burton, Karen L O; Williams, Tracey A; Catchpoole, Sarah E; Brunsdon, Ruth K

    2017-06-01

    The long-term neurocognitive prognosis of childhood onset acute disseminated encephalomyelitis (ADEM) is unclear. This review and quantitative synthesis of the available literature examined whether there are long-term impacts of childhood ADEM on neurocognitive functioning. A search of online databases (MEDLINE, EMBASE, EBSCO CINAHL, PsycINFO and the Cochrane Database of Systematic Reviews) from their inception to October 2015 and reference lists identified 13 papers eligible for inclusion in the systematic review; seven of these were eligible for inclusion in meta-analyses. The systematic review indicated that, at a group level there is a positive long-term neuropsychological outcome from childhood onset ADEM. However, despite the apparent absence of long-term negative impacts of ADEM at a group level, at an individual level impairments in the areas of IQ, attention, executive functioning, processing speed, learning and memory, visuospatial skills and internalising symptoms were found in up to 43% of patients when aggregated across the studies. No significant negative effect of ADEM for any of the neuropsychological domains examined was found in meta-analyses. However, the effects for Processing Speed (r mean = -0.296 (CI 95% = -0.605-0.013)) and Internalising symptoms (r mean = 0.242 (CI 95% = -0.014-0.564)) approached significance (p = 0.06), suggesting a trend towards ADEM leading to long-term reduced processing speed and elevated internalising symptoms. Together, our findings suggest that despite a generally positive neurocognitive outcome post childhood ADEM there are a subset of individuals who can suffer from ongoing specific cognitive impairments. Clinical implications and research priorities are discussed.

  12. Case-control study of childhood acute lymphoblastic leukemia and residential radon exposure.

    Science.gov (United States)

    Lubin, J H; Linet, M S; Boice, J D; Buckley, J; Conrath, S M; Hatch, E E; Kleinerman, R A; Tarone, R E; Wacholder, S; Robison, L L

    1998-02-18

    Several ecologic analyses have shown significant positive associations between mean indoor radon concentrations and risk of leukemia at all ages (acute myeloid leukemia and chronic lymphocytic leukemia) and for children (all leukemia, acute myeloid leukemia, and acute lymphoblastic leukemia [ALL]). As part of an age-matched, case-control study of childhood ALL in the United States, we investigated the association between the incidence of ALL in children under age 15 years and indoor radon exposure. Radon detectors were placed in current and previous homes of subjects where they resided for 6 months or longer. Children were included in analyses if radon measurements covered 70% or more of the 5-year period prior to diagnosis for case subjects (or from birth for case subjects under age 5 years) and the corresponding reference dates for control subjects. Radon levels could be estimated for 97% of the exposure period for the eligible 505 case subjects and 443 control subjects. Mean radon concentration was lower for case subjects (65.4 becquerels per cubic meter [Bqm(-3)]) than for control subjects (79.1 Bqm(-3)). For categories less than 37, 37-73, 74-147, and 148 or more Bqm(-3) of radon exposure, relative risks based on matched case-control pairs were 1.00, 1.22, 0.82, and 1.02, respectively, and were similar to results from an unmatched analysis. There was no association between ALL and radon exposure within subgroups defined by categories of age, income, birth order, birth weight, sex, type of residence, magnetic field exposure, parental age at the subject's birth, parental occupation, or parental smoking habits. In contrast to prior ecologic studies, the results from this analytic study provide no evidence for an association between indoor radon exposure and childhood ALL.

  13. DNA incorporation of 6-thioguanine nucleotides during maintenance therapy of childhood acute lymphoblastic leukaemia and non-Hodgkin lymphoma

    DEFF Research Database (Denmark)

    Hedeland, Rikke L; Hvidt, Kristian; Nersting, Jacob

    2010-01-01

    To explore the DNA incorporation of 6-thioguanine nucleotide levels (DNA-6TGN) during 6-mercaptopurine (6MP) therapy of childhood acute lymphoblastic leukaemia (ALL) and non-Hodgkin lymphoma (NHL) and its relation to erythrocyte levels of their metabolites: 6-thioguanine-nucleotides (E-6TGN), met...

  14. Treatment strategy and results in children treated on three Dutch Childhood Oncology Group acute myeloid leukemia trials

    NARCIS (Netherlands)

    Kardos, G; Zwaan, CM; Kaspers, GJL; de-Graaf, SSN; de Bont, ESJM; Postma, A; Bokkerink, JPM; Weening, RS; van der Does-van den Berg, A; van Wering, ER; Korbijn, C; Hahlen, K

    2005-01-01

    This report describes the long-term follow-up data of three consecutive Dutch Childhood Oncology Group acute myeloid leukemia (AML) protocols. A total of 303 children were diagnosed with AML, of whom 209 were eligible for this report. The first study was the AML-82 protocol. Results were inferior

  15. Mercaptopurine metabolite levels are predictors of bone marrow toxicity following high-dose methotrexate therapy of childhood acute lymphoblastic leukaemia

    DEFF Research Database (Denmark)

    Vang, Sophia Ingeborg; Schmiegelow, Kjeld; Frandsen, Thomas

    2015-01-01

    High-dose methotrexate (HD-MTX) courses with concurrent oral low-dose MTX/6-mercaptopurine (6MP) for childhood acute lymphoblastic leukaemia (ALL) are often followed by neutro- and thrombocytopenia necessitating treatment interruptions. Plasma MTX during HD-MTX therapy guides folinic acid rescue ...

  16. The impact of CYP3A5*3 on risk and prognosis in childhood acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Borst, Louise; Wallerek, Sandra; Dalhoff, Kim

    2011-01-01

    Objectives: Acute lymphoblastic leukemia (ALL) is the most common cancer in childhood; however, little is known of the molecular etiology and environmental exposures causing the disease. Cytochrome P450 3A5 (CYP3A5) plays a crucial role in the catalytic oxidation of endogenous metabolites and toxic...

  17. Polymorphisms in the ABCB1 gene and effect on outcome and toxicity in childhood acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Gregers, J; Gréen, H; Christensen, I J

    2015-01-01

    The membrane transporter P-glycoprotein, encoded by the ABCB1 gene, influences the pharmacokinetics of anti-cancer drugs. We hypothesized that variants of ABCB1 affect outcome and toxicity in childhood acute lymphoblastic leukemia (ALL). We studied 522 Danish children with ALL, 93% of all those...

  18. Long-term results of Dutch Childhood Oncology Group studies for children with acute lymphoblastic leukemia from 1984 to 2004

    NARCIS (Netherlands)

    Kamps, W. A.; van der Pal-de Bruin, K. M.; Veerman, A. J. P.; Fiocco, M.; Bierings, M.; Pieters, R.

    The Dutch Childhood Oncology Group (DCOG) has used two treatment strategies for children with acute lymphoblastic leukemia (ALL) based on Pinkel's St Jude Total Therapy or the Berlin-Frankfurt-Munster (BFM) backbone. In four successive protocols, 1734 children were treated. Studies ALL-6 and ALL-9

  19. Contextual factors associated with health care service utilization for children with acute childhood illnesses in Nigeria.

    Directory of Open Access Journals (Sweden)

    Sulaimon T Adedokun

    Full Text Available To examine the independent contribution of individual, community and state-level factors to health care service utilization for children with acute childhood illnesses in Nigeria.The study was based on secondary analyses of cross-sectional population-based data from the 2013 Nigeria Demographic and Health Survey (DHS. Multilevel logistic regression models were applied to the data on 6,427 under-five children who used or did not use health care service when they were sick (level 1, nested within 896 communities (level 2 from 37 states (level 3.About one-quarter of the mothers were between 15 and 24 years old and almost half of them did not have formal education (47%. While only 30% of the children utilized health service when they were sick, close to 67% lived in the rural area. In the fully adjusted model, mothers with higher education attainment (Adjusted odds ratio [aOR] = 1.63; 95% credible interval [CrI] = 1.31-2.03, from rich households (aOR = 1.76; 95% CrI = 1.35-2.25, with access to media (radio, television or magazine (aOR = 1.18; 95% CrI = 1.08-1.29, and engaging in employment (aOR = 1.18; 95% CrI = 1.02-1.37 were significantly more likely to have used healthcare services for acute childhood illnesses. On the other hand, women who experienced difficulty getting to health facilities (aOR = 0.87; 95% CrI = 0.75-0.99 were less likely to have used health service for their children.Our findings highlight that utilization of healthcare service for acute childhood illnesses was influenced by not only maternal factors but also community-level factors, suggesting that public health strategies should recognise this complex web of individual composition and contextual composition factors to guide provision of healthcare services. Such interventions could include: increase in female school enrolment, provision of interest-free loans for small and medium scale enterprises, introduction of mobile clinics and establishment of more primary health care

  20. Clinical features and early treatment response of central nervous system involvement in childhood acute lymphoblastic leukemia.

    Science.gov (United States)

    Levinsen, Mette; Taskinen, Mervi; Abrahamsson, Jonas; Forestier, Erik; Frandsen, Thomas L; Harila-Saari, Arja; Heyman, Mats; Jonsson, Olafur G; Lähteenmäki, Päivi M; Lausen, Birgitte; Vaitkevičienė, Goda; Asberg, Ann; Schmiegelow, Kjeld

    2014-08-01

    Central nervous system (CNS) involvement in childhood acute lymphoblastic leukemia (ALL) remains a therapeutic challenge. To explore leukemia characteristics of patients with CNS involvement at ALL diagnosis, we analyzed clinical features and early treatment response of 744 patients on Nordic-Baltic trials. CNS status was classified as CNS1 (no CSF blasts), CNS2 ( 0.15). The 12-year event-free survival for patients with leukemic mass on neuroimaging did not differ from patients with negative or no scan (0.50 vs. 0.60; P = 0.7) or between patients with symptoms or signs suggestive of CNS leukemia and patients without such characteristics (0.50 vs. 0.61; P = 0.2). CNS involvement at diagnosis is associated with adverse prognostic features but does not indicate a less chemosensitive leukemia. © 2014 Wiley Periodicals, Inc.

  1. Early life exposure to infections and risk of childhood acute lymphoblastic leukemia

    Science.gov (United States)

    Urayama, Kevin Y.; Ma, Xiaomei; Selvin, Steve; Metayer, Catherine; Chokkalingam, Anand P.; Wiemels, Joseph L.; Does, Monique; Chang, Jeffrey; Wong, Alan; Trachtenberg, Elizabeth; Buffler, Patricia A.

    2011-01-01

    Evidence from a growing number of studies indicates that exposure to common infections early in life may be protective against childhood acute lymphoblastic leukemia (ALL). We examined the relationship between three measures of early life exposure to infections—daycare attendance, birth order and common childhood infections in infancy—with the risk of ALL in non-Hispanic white and Hispanic children, two ethnicities that show sociodemographic differences. The analysis included 669 ALL cases (284 non-Hispanic whites and 385 Hispanics) and 977 controls (458 non-Hispanic whites and 519 Hispanics) ages 1–14 years enrolled in the Northern California Childhood Leukemia Study (NCCLS). When the three measures were evaluated separately, daycare attendance by the age of 6 months (odds ratio [OR] for each thousand child-hours of exposure = 0.90, 95% confidence interval [CI]: 0.82–1.00) and birth order (OR for having an older sibling = 0.68, 95% CI: 0.50–0.92) were associated with a reduced risk of ALL among non-Hispanic white children but not Hispanic children, whereas ear infection before age 6 months was protective in both ethnic groups. When the three measures were assessed simultaneously, the influence of daycare attendance (OR = 0.83, 95% CI: 0.73–0.94) and having an older sibling (OR = 0.59, 95% CI: 0.43–0.83) became stronger for non-Hispanic white children. In Hispanic children, a strong reduction in risk associated with ear infections persisted (OR = 0.45, 95% CI: 0.25–0.79). Evidence of a protective role for infection-related exposures early in life is supported by findings in both the non-Hispanic white and Hispanic populations within the NCCLS. PMID:21280034

  2. Implication of IRF4 aberrant gene expression in the acute leukemias of childhood.

    Directory of Open Access Journals (Sweden)

    Maria Adamaki

    Full Text Available The most frequent targets of genetic alterations in human leukemias are transcription factor genes with essential functions in normal blood cell development. The Interferon Regulatory Factor 4 (IRF4 gene encodes a transcription factor important for key developmental stages of hematopoiesis, with known oncogenic implications in multiple myeloma, adult leukemias and lymphomas. Very few studies have reported an association of IRF4 with childhood malignancy, whereas high transcript levels have been observed in the more mature immunophenotype of ALL. Our aim was to investigate the expression levels of IRF4 in the diagnostic samples of pediatric leukemias and compare them to those of healthy controls, in order to determine aberrant gene expression and whether it extends to leukemic subtypes other than the relatively mature ALL subpopulation. Quantitative real-time RT-PCR methodology was used to investigate IRF4 expression in 58 children with acute leukemias, 4 leukemic cell lines and 20 healthy children. We show that aberrant IRF4 gene expression is implicated in a variety of leukemic subtypes; higher transcript levels appear in the more immature B-common ALL subtype and in T-cell than in B-cell leukemias, with the highest expression levels appearing in the AML group. Interestingly, we show that childhood leukemia, irrespective of subtype or cell maturation stage, is characterised by a minimum of approximately twice the amount of IRF4 gene expression encountered in healthy children. A statistically significant correlation also appeared to exist between high IRF4 expression and relapse. Our results show that ectopic expression of IRF4 follows the reverse expression pattern of what is encountered in normal B-cell development and that there might be a dose-dependency of childhood leukemia for aberrantly expressed IRF4, a characteristic that could be explored therapeutically. It is also suggested that high IRF4 expression might be used as an additional

  3. Identification of germline susceptibility loci in ETV6-RUNX1-rearranged childhood acute lymphoblastic leukemia

    Science.gov (United States)

    Ellinghaus, E; Stanulla, M; Richter, G; Ellinghaus, D; te Kronnie, G; Cario, G; Cazzaniga, G; Horstmann, M; Panzer Grümayer, R; Cavé, H; Trka, J; Cinek, O; Teigler-Schlegel, A; ElSharawy, A; Häsler, R; Nebel, A; Meissner, B; Bartram, T; Lescai, F; Franceschi, C; Giordan, M; Nürnberg, P; Heinzow, B; Zimmermann, M; Schreiber, S; Schrappe, M; Franke, A

    2012-01-01

    Acute lymphoblastic leukemia (ALL) is a malignant disease of the white blood cells. The etiology of ALL is believed to be multifactorial and likely to involve an interplay of environmental and genetic variables. We performed a genome-wide association study of 355 750 single-nucleotide polymorphisms (SNPs) in 474 controls and 419 childhood ALL cases characterized by a t(12;21)(p13;q22) — the most common chromosomal translocation observed in childhood ALL — which leads to an ETV6–RUNX1 gene fusion. The eight most strongly associated SNPs were followed-up in 951 ETV6-RUNX1-positive cases and 3061 controls from Germany/Austria and Italy, respectively. We identified a novel, genome-wide significant risk locus at 3q28 (TP63, rs17505102, PCMH=8.94 × 10−9, OR=0.65). The separate analysis of the combined German/Austrian sample only, revealed additional genome-wide significant associations at 11q11 (OR8U8, rs1945213, P=9.14 × 10−11, OR=0.69) and 8p21.3 (near INTS10, rs920590, P=6.12 × 10−9, OR=1.36). These associations and another association at 11p11.2 (PTPRJ, rs3942852, P=4.95 × 10−7, OR=0.72) remained significant in the German/Austrian replication panel after correction for multiple testing. Our findings demonstrate that germline genetic variation can specifically contribute to the risk of ETV6–RUNX1-positive childhood ALL. The identification of TP63 and PTPRJ as susceptibility genes emphasize the role of the TP53 gene family and the importance of proteins regulating cellular processes in connection with tumorigenesis. PMID:22076464

  4. Impaired mitochondrial function is abrogated by dexrazoxane in doxorubicin-treated childhood acute lymphoblastic leukemia survivors.

    Science.gov (United States)

    Lipshultz, Steven E; Anderson, Lynn M; Miller, Tracie L; Gerschenson, Mariana; Stevenson, Kristen E; Neuberg, Donna S; Franco, Vivian I; LiButti, Daniel E; Silverman, Lewis B; Vrooman, Lynda M; Sallan, Stephen E

    2016-03-15

    Impaired cardiac function in doxorubicin-treated childhood cancer survivors is partly mediated by the disruption of mitochondrial energy production. Doxorubicin intercalates into mitochondrial DNA (mtDNA) and disrupts genes encoding for polypeptides that make adenosine triphosphate. This cross-sectional study examined mtDNA copy numbers per cell and oxidative phosphorylation (OXPHOS) in peripheral blood mononuclear cells (PBMCs) in 64 childhood survivors of high-risk acute lymphoblastic leukemia (ALL) who had been treated on Dana-Farber Cancer Institute childhood ALL protocols and had received doxorubicin alone (42%) or doxorubicin with the cardioprotectant dexrazoxane (58%). The number of mtDNA copies per cell and the OXPHOS enzyme activity of nicotinamide adenine dinucleotide dehydrogenase (complex I [CI]) and cytochrome c oxidase (complex IV [CIV]) were measured with quantitative real-time polymerase chain reaction immunoassays and thin-layer chromatography, respectively. At a median follow-up of 7.8 years after treatment, the median number of mtDNA copies per cell for patients treated with doxorubicin alone (1106.3) was significantly higher than the median number for those who had also received dexrazoxane (310.5; P = .001). No significant differences were detected between the groups for CI or CIV activity. Doxorubicin-treated survivors had an increased number of PBMC mtDNA copies per cell, and concomitant use of dexrazoxane was associated with a lower number of mtDNA copies per cell. Because of a possible compensatory increase in mtDNA copies per cell to maintain mitochondrial function in the setting of mitochondrial dysfunction, overall OXPHOS activity was not different between the groups. The long-term sustainability of this compensatory response in these survivors at risk for cardiac dysfunction over their lifespan is concerning. © 2016 American Cancer Society.

  5. Combination Chemotherapy and Imatinib Mesylate in Treating Children With Relapsed Acute Lymphoblastic Leukemia

    Science.gov (United States)

    2013-10-07

    L1 Childhood Acute Lymphoblastic Leukemia; L2 Childhood Acute Lymphoblastic Leukemia; Non-T, Non-B Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; T-cell Childhood Acute Lymphoblastic Leukemia

  6. Family circumstances and survival from childhood acute lymphoblastic leukaemia in West Germany.

    Science.gov (United States)

    Erdmann, Friederike; Kaatsch, Peter; Schüz, Joachim

    2015-04-01

    Little is known about the relationship between family characteristics and survival from childhood acute lymphoblastic leukaemia (ALL), which we studied for the first time in German children. ALL cases were diagnosed between 1992 and 1994 and information on family characteristics was collected during a previously conducted nationwide case-control study. Children were followed for 10 years after diagnosis, as few disease-related events occur afterwards. Cox proportional hazards models estimating hazard ratios (HR) were calculated using overall as well as event-free survival methods. Second born children showed statistically significant better survival compared to first or later born children, with HRs ranging between 0.54 and 0.64 compared to firstborns. Somewhat poorer survival was observed for children having 3 or more siblings. A relationship was found for parental age at child's diagnosis, with poorer survival for children with younger parents (≤25 years of age at child's diagnosis), or with older fathers. The HR was statistically significant for fathers being ≥41years of age (HR of 2.1). No relationship between degree of urbanization of the place of residence at diagnosis and ALL survival was observed. Family circumstances may have an impact on survival from childhood ALL in Germany. Further research is warranted to elaborate the relationship of specific family characteristics and ALL survival and to investigate possible differential adherence to therapy and interactions with physicians. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. Health-related quality of life assessment in Indonesian childhood acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    Sutaryo

    2008-11-01

    Full Text Available Abstract Background Most studies on Health-related Quality of Life (HRQOL in children with cancer were conducted in developed countries. The aims of this study were to assess the HRQOL in childhood acute lymphoblastic leukemia (ALL patients in Indonesia and to assess the influence of demographic and medical characteristics on HRQOL. Methods After cultural linguistic validation, a cross-sectional study of HRQOL was conducted with childhood ALL patients and their guardians in various phases of treatment using the Pediatric Quality of Life Inventory™ (PedsQL™ 4.0 Generic Core Scale and the Pediatric Quality of Life Inventory™ (PedsQL™ 3.0 Cancer Module. Results Ninety-eight guardians and 55 patients participated. The internal consistency of both scales ranged from 0.57 to 0.92. HRQOL of Indonesian patients was comparable with those in developed countries. There were moderate to good correlations between self-reports and proxy-reports, however guardians tended to report worse HRQOL than patients. Children of the 2–5 year-group significantly had more problems in procedural anxiety, treatment anxiety and communication subscales than in older groups (p Conclusion Younger children had more problems in procedural anxiety, treatment anxiety and communication subscales. Therefore, special care during intervention procedures is needed to promote their normal development. Psychosocial support should be provided to children and their parents to facilitate their coping with disease and its treatment.

  8. Altered neutrophil immunophenotypes in childhood B-cell precursor acute lymphoblastic leukemia

    Science.gov (United States)

    Oliveira, Elen; Bacelar, Thiago S.; Ciudad, Juana; Ribeiro, Maria Cecília M.; Garcia, Daniela R.N.; Sedek, Lukasz; Maia, Simone F.; Aranha, Daniel B.; Machado, Indyara C.; Ikeda, Arissa; Baglioli, Bianca F.; Lopez-Duarte, Nathalia; Teixeira, Lisandra A. C.; Szczepanski, Tomasz; Silva, Maria Luiza M.; Land, Marcelo G.P.

    2016-01-01

    An increasing number of evidences suggest a genetic predisposition in acute lymphoblastic leukemia (ALL) that might favor the occurrence of the driver genetic alterations. Such genetic background might also translate into phenotypic alterations of residual hematopoietic cells. Whether such phenotypic alterations are present in bone marrow (BM) cells from childhood B-cell precursor (BCP)-ALL remains to be investigated. Here we analyzed the immunophenotypic profile of BM and peripheral blood (PB) maturing/matured neutrophils from 118 children with BCP-ALL and their relationship with the features of the disease. Our results showed altered neutrophil phenotypes in most (77%) BCP-ALL cases. The most frequently altered marker was CD10 (53%), followed by CD33 (34%), CD13 (15%), CD15/CD65 (10%) and CD123 (7%). Of note, patients with altered neutrophil phenotypes had younger age (p = 0.03) and lower percentages of BM maturing neutrophils (p = 0.004) together with greater BM lymphocyte (p = 0.04), and mature B-cell (p = 0.03) counts. No significant association was found between an altered neutrophil phenotype and other disease features. These findings point out the potential existence of an altered residual hematopoiesis in most childhood BCP-ALL cases. PMID:27028865

  9. Approach to prediagnostic clinical semiology, noticed by mothers, of childhood acute lymphoblastic leukemia.

    Science.gov (United States)

    Castro-Jiménez, Miguel Ángel; Rueda-Arenas, Ernesto; Cabrera-Rodríguez, Daladier

    2015-08-01

    Recognizing early symptoms of acute lymphoblastic leukemia (ALL) may help to make an early diagnosis. The objective of this study is to identify clinical manifestations preceding the diagnosis of childhood ALL from the maternal perspective and to establish the time elapsed from the first manifestation to the diagnosis. Six hospitals located in Bogotá and Bucaramanga (Colombia) participated. Cases consisted of children under 15 years old with incidental diagnosis of ALL between January 2000 and March 2005. Data on sociodemographic characteristics, pre diagnostic clinical manifestations, first symptom, and time to diagnosis were collected during interviews with mothers. Medians, ranges and proportions were estimated. P values below 0.05 were considered significant. One hundred and twenty-eight cases were analyzed. Pallor (83.6%), loss of appetite (72.6%), weight loss (62.5%), andbleeding into the skin (39.1%) were the most common symptoms preceding diagnosis. The delay between the occurrence of the first symptom and the diagnosis of ALL depends on what the first manifestation is, and it maybe shorter when there is evidence of hemorrhage (median= 14 days). The presence of palpable lymph nodes in the armpits was more significant in girls than in boys (p= 0.04). Childhood ALL symptomatology in the prediagnostic stage is not specific to this disease; however, the clinical sign and time since its occurrence may serve as a guide in the early stage of this disease.

  10. Parental Perceptions of Obesity and Obesity Risk Associated With Childhood Acute Lymphoblastic Leukemia.

    Science.gov (United States)

    Jones, Gary L; McClellan, Wendy; Raman, Sripriya; Sherman, Ashley; Guest, Erin; August, Keith

    2017-07-01

    The prevalence of obesity and related comorbidities in survivors of childhood acute lymphoblastic leukemia (ALL) is well established and ranges anywhere from 29% to 69% depending on the study. We sought to explore the awareness of parents of survivors of childhood ALL regarding the increased risk of obesity and their perceptions regarding the overall health of their child. One hundred twenty-one parents of 99 survivors of pediatric ALL completed surveys regarding perceptions of obesity risk in survivors. Eighty percent of parents of overweight and obese survivors correctly identified their child as "a little overweight" or "overweight." Few parents recalled discussing weight gain (21%) or obesity risk (36%) with their practitioner. Parents that did recall having these discussions and/or reported a decreased level of posttherapy activity in their child were more likely to be concerned about their child's weight status. Improved awareness and education regarding the risk of obesity and associated comorbid conditions may provide an avenue for future prevention of obesity in survivors of pediatric ALL. Discussion and education regarding a healthy lifestyle, including proper diet and exercise, should be incorporated early in routine patient visits.

  11. Disseminated Pasteurella multocida infection: Cellulitis, osteomyelitis, and myositis.

    Science.gov (United States)

    Marcantonio, Yasmin C; Kulkarni, Prathit A; Sachs, Shira; Ting, Kevin; Lee, Jennifer; Mendoza, Daniel

    2017-01-01

    A 67-year-old man with poorly controlled type II diabetes mellitus was evaluated for right lower extremity erythema and swelling and left-sided lower back pain. He was found to have Pasteurella multocida bacteremia; magnetic resonance imaging showed osteomyelitis of the lumbar spine with myositis in the adjacent left paraspinal muscles. He was initially treated with intravenous antibiotics and was later transitioned to oral amoxicillin. He recovered completely with six weeks of antimicrobial therapy.

  12. An unexpectedly high incidence of acute childhood diarrhea in Koot-Abdollah, Ahwaz, Iran.

    Science.gov (United States)

    Kolahi, Ali-Asghar; Rastegarpour, Ali; Abadi, Alireza; Gachkar, Latif

    2010-07-01

    Koot-Abdollah is a neighborhood in Ahwaz, in the southeast of Iran, susceptible to public health hazards due to a number of factors, including a low level of personal hygiene, inappropriate community sanitation, and a high level of environmental and water pollution. This study was designed to measure the incidence of acute childhood diarrhea in this neighborhood. This was a descriptive population-based study. Via multistage sampling, data were collected by interviewing the mothers in their homes. Reported 95% confidence intervals included a finite population correction factor and accounted for the cluster sampling design. The study included 2016 children aged 6 to 60 months. Overall, 725 (36.0%) of the children studied had experienced an episode of acute diarrhea during the previous two weeks. In other words, the children demonstrated a rate of diarrhea per 100 person-years of 936 for the studied period, which was a time period expected to reveal the lowest possible incidence of diarrhea. The incidence of diarrhea per two weeks in Koot-Abdollah is exceptionally high. The limitation of available drinking water, warm weather, illiteracy, poverty, and low incomes, in addition to the low level of sanitation and personal hygiene and extreme environmental pollution contribute to this high incidence. Copyright 2010 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  13. Genome‐wide analysis of cytogenetic aberrations in ETV6/RUNX1‐positive childhood acute lymphoblastic leukaemia

    DEFF Research Database (Denmark)

    Borst, Louise; Wesolowska, Agata; Joshi, Tejal

    2012-01-01

    The chromosomal translocation t(12;21) resulting in the ETV6/RUNX1 fusion gene is the most frequent structural cytogenetic abnormality among patients with childhood acute lymphoblastic leukaemia (ALL). We investigated 62 ETV6/RUNX1‐positive childhood ALL patients by single nucleotide polymorphism...... array to explore acquired copy number alterations (CNAs) at diagnosis. The mean number of CNAs was 2·82 (range 0–14). Concordance with available G‐band karyotyping and comparative genomic hybridization was 93%. Based on three major protein‐protein complexes disrupted by these CNAs, patients could...

  14. [Correlation between level of metallic elements in urine and childhood acute leukemia].

    Science.gov (United States)

    Zhu, Sha; Zhang, Yan; Gao, Yu; Wang, Xiao-jin; Chen, Tao; Yang, You; Shi, Rong; Jin, Ping; Tian, Ying; Shen, Xiao-ming

    2011-02-01

    To explore the relation between the level of metallic elements in urine and childhood acute leukemia. A total of 71 patients under 15 years old who were newly diagnosed with acute leukemia between September 2007 and August 2008 without Downs' syndrome or other tumors, and 113 gender- and age-matched controls without tumors or congenital diseases were enrolled for the case-control study. The general data and potential risk factors were obtained by questionnaires. Inductively coupled plasma mass spectrometry (ICP-MS) was used to determine the metal concentrations in urine, which was collected randomly before chemotherapy. Logistic regression model was performed for univariate and multivariate analysis. The questionnaire showed that there was significant difference in the proportion of children whose mothers had taken iron supplements during or 3 months before pregnancy between case group and control group, which was 28.2% (20/71) and 14.2% (16/113) respectively (Wald χ(2) = 5.438, P = 0.02). Univariate logistic regression analysis showed that levels of vanadium, manganese, iron, cobalt, copper, arsenic, and barium in urine from case group were all higher than those of control group with significant difference. The median values for vanadium in urine from case and control groups were 5.39 and 3.04 ng/mg creatinine (Wald χ(2) = 9.03, P < 0.05); the median values for manganese were respectively 4.46 and 2.44 ng/mg creatinine (Wald χ(2) = 10.57, P < 0.05); the median values for iron were separately 58.69 and 14.09 ng/mg creatinine (Wald χ(2) = 13.41, P < 0.05); the median values for cobalt were respectively 0.98 and 0.77 ng/mg creatinine (Wald χ(2) = 4.46, P < 0.05); the median values for copper were 61.17 and 10.90 ng/mg creatinine (Wald χ(2) = 8.15, P < 0.05); the median values for arsenic were respectively 55.93 and 36.11 ng/mg creatinine (Wald χ(2) = 4.57, P < 0.05); and the median values for barium were 8.55 and 2.87 ng/mg creatinine (Wald χ(2) = 4.82, P < 0

  15. Altered brain function in new onset childhood acute lymphoblastic leukemia before chemotherapy: A resting-state fMRI study.

    Science.gov (United States)

    Hu, Zhanqi; Zou, Dongfang; Mai, Huirong; Yuan, Xiuli; Wang, Lihong; Li, Yue; Liao, Jianxiang; Liu, Liwei; Liu, Guosheng; Zeng, Hongwu; Wen, Feiqiu

    2017-10-01

    Cognitive impairments had been reported in childhood acute lymphoblastic leukemia, what caused the impairments needed to be demonstrated, chemotherapy-related or the disease itself. The primary aim of this exploratory investigation was to determine if there were changes in brain function of children with acute lymphoblastic leukemia before chemotherapy. In this study, we advanced a measure named regional homogeneity to evaluate the resting-state brain activities, intelligence quotient test was performed at same time. Using regional homogeneity, we first investigated the resting state brain function in patients with new onset childhood acute lymphoblastic leukemia before chemotherapy, healthy children as control. The decreased ReHo values were mainly founded in the default mode network and left frontal lobe, bilateral inferior parietal lobule, bilateral temporal lobe, bilateral occipital lobe, precentral gyrus, bilateral cerebellum in the newly diagnosed acute lymphoblastic leukemia patients compared with the healthy control. While in contrast, increased ReHo values were mainly shown in the right frontal lobe (language area), superior frontal gyrus-R, middle frontal gyrus-R and inferior parietal lobule-R for acute lymphoblastic leukemia patients group. There were no significant differences for intelligence quotient measurements between the acute lymphoblastic leukemia patient group and the healthy control in performance intelligence quotient, verbal intelligence quotient, total intelligence quotient. The altered brain functions are associated with cognitive change and language, it is suggested that there may be cognition impairment before the chemotherapy. Regional homogeneity by functional magnetic resonance image is a sensitive way for early detection on brain damage in childhood acute lymphoblastic leukemia. Copyright © 2017 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  16. A randomized controlled trial of intranasal-midazolam versus intravenous-diazepam for acute childhood seizures.

    Science.gov (United States)

    Thakker, Arpita; Shanbag, Preeti

    2013-02-01

    The objective of this study is to compare the safety and efficacy of midazolam given intranasally with diazepam given intravenously in the treatment of acute childhood seizures. A randomized controlled study was conducted in a pediatric emergency department in a tertiary general hospital. Fifty children aged from 1 month to 12 years presenting with acute seizures of at least 10 min duration were enrolled during a 12 month period. Intranasal midazolam (0.2 mg/kg) and intravenous diazepam (0.3 mg/kg) were administered. The main outcome measures were interval between arrival at hospital and starting treatment and interval between arrival at hospital and cessation of seizures. Intranasal midazolam and intravenous diazepam were equally effective. Overall 18 of 27 seizures were controlled with midazolam and 15 of 23 with diazepam. The mean interval between arrival at hospital and starting treatment was significantly shorter in the midazolam group [3.37 min (SD 2.46)] as compared to the diazepam group [14.13 min (SD 3.39)]. The mean interval between cessation of seizures and arrival at hospital was significantly shorter in the midazolam group [6.67 min (SD 3.12)] as compared to the diazepam group [17.18 min (SD 5.09)]. The mean interval between control of seizures and administration of the drug was shorter in the diazepam group [2.67 min (SD 2.31)] as compared to the midazolam group [3.01 min (SD 2.79)]. No significant side effects were observed in either group. Seizures were controlled more quickly with intravenous diazepam than with intranasal midazolam. Midazolam was as safe and effective as diazepam. The overall interval between arrival at hospital and cessation of seizures was shorter with intranasal midazolam than with intravenous diazepam. The intranasal route can be possibly used not only in medical centres, but with appropriate instruction by the parents of children with acute seizures at home.

  17. Orbital and ocular manifestations of acute childhood leukemia: clinical and statistical analysis of 180 patients.

    Science.gov (United States)

    Russo, V; Scott, I U; Querques, G; Stella, A; Barone, A; Delle Noci, N

    2008-01-01

    To investigate the association between presence of orbital or ocular lesions and type and stage of leukemia and to investigate whether orbital and ocular lesions are significant in predicting leukemia prognosis. The authors evaluated 180 patients with acute childhood leukemia. Lesions associated with leukemia may be classified as specific (due to leukemic infiltration of various ocular tissues), nonspecific (due to one of the secondary complications), or iatrogenic manifestations caused by chemotherapy. Risk-based treatment assignment is based on clinical and laboratory features at diagnosis. Children with presenting white blood cell count below 50,000 mm3 are considered at standard risk for treatment failure, while all others are considered at high risk for treatment failure. Specific lesions were noted in 66% of patients with acute myeloid leukemia (AML) and 11.5% patients with acute lymphocytic leukemia (ALL) (pleukemia than in patients with standard risk leukemia. Orbital or ocular lesions were noted more commonly in patients with AML (66.6%) compared to patients with ALL (15.1%). In both the AML and ALL groups, there was a higher frequency of leukemic relapses in the bone marrow and/or central nervous system in patients with specific lesions (63.1%) compared to patients with nonspecific lesions (42%), and in patients without orbital or ocular lesions (29.2%) (p<0.05). In both the AML and ALL groups, the presence of specific orbital or ocular lesions was associated with a higher frequency of bone marrow relapses and CNS involvement (p<0.05), leading to a lower survival rate.

  18. Involvement of MTHFR and TPMT genes in susceptibility to childhood acute lymphoblastic leukemia (ALL) in Mexicans.

    Science.gov (United States)

    Gutiérrez-Álvarez, Ossyneidee; Lares-Asseff, Ismael; Galaviz-Hernández, Carlos; Reyes-Espinoza, Elio-Aarón; Almanza-Reyes, Horacio; Sosa-Macías, Martha; Chairez Hernández, Isaías; Salas-Pacheco, José-Manuel; Bailón-Soto, Claudia E

    2016-03-01

    Folate metabolism plays an essential role in the processes of DNA synthesis and methylation. Deviations in the folate flux resulting from single-nucleotide polymorphisms in genes encoding folate-dependent enzymes may affect the susceptibility to leukemia. This case-control study aimed to assess associations among MTHFR (C677T, A1298C) and TPMT (*2, *3A) mutations as well as to evaluate the synergistic effects of combined genotypes for both genes. Therefore, these genetic variants may lead to childhood acute lymphoblastic leukemia (ALL) susceptibility, in a Mexican population study. DNA samples obtained from 70 children with ALL and 152 age-matched controls (range, 1-15 years) were analyzed by real-time reverse transcription polymerase chain reaction (RT-qPCR) to detect MTHFR C677T and A1298C and TPMT*2 and TPMT*3A genotypes. The frequency of the MTHFR A1298C CC genotype was statistically significant (odds ratio [OR], 6.48; 95% 95% confidence intervals [CI], 1.26-33.2; p=0.025). In addition, the combined 677CC+1298AC genotype exhibited a statistically significant result (OR, 0.23; 95% CI, 0.06-0.82; p=0.023). No significant results were obtained from the MTHFR (C677T CT, C677T TT) or TPMT (*2, *3A) genotypes. More importantly, no association between the synergistic effects of either gene (MTHFR and/or TPMT) and susceptibility to ALL was found. The MTHFR A1298C CC genotype was associated with an increased risk of developing childhood ALL. However, a decreased risk to ALL with the combination of MTHFR 677CC+1298AC genotypes was found.

  19. EZH2 mutations and promoter hypermethylation in childhood acute lymphoblastic leukemia.

    Science.gov (United States)

    Schäfer, Vivien; Ernst, Jana; Rinke, Jenny; Winkelmann, Nils; Beck, James F; Hochhaus, Andreas; Gruhn, Bernd; Ernst, Thomas

    2016-07-01

    Acute lymphoblastic leukemia (ALL) is the most common malignancy in children and young adults. The polycomb repressive complex 2 (PRC2) has been identified as one of the most frequently mutated epigenetic protein complexes in hematologic cancers. PRC2 acts as an epigenetic repressor through histone H3 lysine 27 trimethylation (H3K27me3), catalyzed by the histone methyltransferase enhancer of zeste homolog 2 protein (EZH2). To study the prevalence and clinical impact of PRC2 aberrations in an unselected childhood ALL cohort (n = 152), we performed PRC2 mutational screenings by Sanger sequencing and promoter methylation analyses by quantitative pyrosequencing for the three PRC2 core component genes EZH2, suppressor of zeste 12 (SUZ12), and embryonic ectoderm development (EED). Targeted deep next-generation sequencing of 30 frequently mutated genes in leukemia was performed to search for cooperating mutations in patients harboring PRC2 aberrations. Finally, the functional consequence of EZH2 promoter hypermethylation on H3K27me3 was studied by Western blot analyses of primary cells. Loss-of-function EZH2 mutations were detected in 2/152 (1.3 %) patients with common-ALL and early T-cell precursor (ETP)-ALL, respectively. In one patient, targeted deep sequencing identified cooperating mutations in ASXL1 and TET2. EZH2 promoter hypermethylation was found in one patient with ETP-ALL which led to reduced H3K27me3. In comparison with healthy children, the EZH2 promoter was significantly higher methylated in T-ALL patients. No mutations or promoter methylation changes were identified for SUZ12 or EED genes, respectively. Although PRC2 aberrations seem to be rare in childhood ALL, our findings indicate that EZH2 aberrations might contribute to the disease in specific cases. Hereby, EZH2 promoter hypermethylation might have functionally similar consequences as loss-of-function mutations.

  20. DNA methylation as a potential mediator of environmental risks in the development of childhood acute lymphoblastic leukemia

    Science.gov (United States)

    Timms, Jessica A; Relton, Caroline L; Rankin, Judith; Strathdee, Gordon; McKay, Jill A

    2016-01-01

    5-year survival rate for childhood acute lymphoblastic leukemia (ALL) has risen to approximately 90%, yet the causal disease pathway is still poorly understood. Evidence suggests multiple ‘hits’ are required for disease progression; an initial genetic abnormality followed by additional secondary ‘hits’. It is plausible that environmental influences may trigger these secondary hits, and with the peak incidence of diagnosis between 2 and 5 years of age, early life exposures are likely to be key. DNA methylation can be modified by many environmental exposures and is dramatically altered in cancers, including childhood ALL. Here we explore the potential that DNA methylation may be involved in the causal pathway toward disease by acting as a mediator between established environmental factors and childhood ALL development. PMID:27035209

  1. MINIMAL REQUIREMENTS FOR THE DIAGNOSIS, CLASSIFICATION, AND EVALUATION OF THE TREATMENT OF CHILDHOOD ACUTE LYMPHOBLASTIC-LEUKEMIA (ALL) IN THE BFM FAMILY COOPERATIVE GROUP

    NARCIS (Netherlands)

    VANDERDOESVANDENBERG, A; BARTRAM, CR; BASSO, G; BENOIT, YCM; BIONDI, A; DEBATIN, KM; HAAS, OA; HARBOTT, J; KAMPS, WA; KOLLER, U; LAMPERT, F; LUDWIG, WD; NIEMEYER, CM; VANWERING, ER

    1992-01-01

    Minimal requirements and their rationale for the diagnosis and the response to treatment in childhood acute lymphoblastic leukemia (ALL) were defined in the recently instituted "BFM-Family"-Group, in which the German, Austrian, Dutch, Italian, Belgian, French and Hungarian childhood leukemia study

  2. Therapy-Related Myelodysplastic Syndrome Following Treatment for Childhood Acute Lymphoblastic Leukemia: Outcome of Patients Registered in the EWOG-MDS 98/06 Studies

    DEFF Research Database (Denmark)

    Strahm, Birgitte; Amann, Roland; De Moerloose, Barbara

    Objective: Therapy-related myelodysplastic syndrome (tMDS) following treatment of childhood acute lymphoblastic leukemia (ALL) is one of the most frequently observed secondary malignancies in survivors of childhood cancer. Allogeneic stem cell transplantation (SCT) is the only curative treatment...

  3. Generalized myositis mimicking polymyositis associated with chronic active Epstein-Barr virus infection.

    Science.gov (United States)

    Uchiyama, Tomoyuki; Arai, Kimito; Yamamoto-Tabata, Takako; Hirai, Kanji; Kishimoto, Kouji; Nakamura, Yoshiko; Hattori, Takamichi

    2005-05-01

    Chronic generalized myositis has not so far been reported as a complication of chronic active Epstein-Barr virus infection (CAEBV). We encountered three patients with chronic generalized myositis mimicking polymyositis associated with CAEBV. To clarify the pathological character of this myositis, we investigated the distribution, clonality, and the immunophenotype of EBV-infected cells and lymphocytes infiltrating in muscles. Clinically, two patients showed symmetrical proximal weakness and muscle atrophy as the initial and main symptom. Although the condition resembled polymyositis, they had also lingual and/or orbital myositis. The other patient showed generalized myositis at the late phase of CAEBV. In all of them, immunotherapy was ineffective and prognosis was poor. Intramuscular infiltrating lymphocytes in our patients were mainly CD45RO+, CD3+, CD4-, CD8-, TCR betaF1-, TCR deltaTCS1-, CD56-, CD79a-, CD21-, HLA-DR+, ZEBRA -, LMP1-, and EBER+ T cells. Oligoclonal expansion of EBV-infected T cells was shown in the muscles. However, there were no malignant lymphocytes. This new form of myositis must be distinguished from polymyositis and the other conventional forms of myositis. Careful investigation of hidden CAEBV is recommended when patients present with steroid non-responsive chronic progressive generalized myositis, in particular, with lingual or orbital involvement.

  4. Myositis ossificans circumscripta, secondary to high-velocity gunshot and fragment wound that causes sciatica.

    Science.gov (United States)

    Gokkus, Kemal; Sagtas, Ergin; Suslu, Feride Ekimler; Aydin, Ahmet Turan

    2013-10-17

    This report concerns an unusual cause of sciatica. The case presented is of a young man with myositis ossificans that resulted in sciatica and was treated with en bloc excision and low-dose radiotherapy and indomethacine. The aim of this study was to explain the different diagnostic properties of myositis ossificans around the hip and non-classic causes of sciatica.

  5. Clinical relevance of in vitro chemoresistance in childhood acute myeloid leukemia.

    Science.gov (United States)

    Yamada, S; Hongo, T; Okada, S; Watanabe, C; Fujii, Y; Ohzeki, T

    2001-12-01

    To determine the clinical relevance of in vitro drug chemoresistance in childhood acute myeloid leukemia, we used an MTT assay to test leukemic cells from 132 newly diagnosed children. Patients were diagnosed according to the French-American-British (FAB) classification as follows: M0 (n = 12), M1 (n = 16), M2 (n = 53), M4 (n = 17), M5 (n = 19) and M7 (n = 15). The results revealed that, compared to leukemic cells from complete-responders (n = 107), those from non-responders who failed induction therapy (n = 17) were 1.4 to 5.0 times more resistant in vitro to cytarabine (P = 0.005), melphalan (P = 0.003), etoposide (P = 0.011), L-asparaginase (P = 0.017), aclarubicin (P = 0.026) and dexamethasone (P = 0.039). For seven other drugs tested, the median lethal dose of 70% and leukemic cell survival of non-responders were higher than those of complete-responders, but the difference was not statistically significant. We sought correlations between FAB subtypes and in vitro drug resistance. Leukemias of the FAB M4 and M5 subtype were more sensitive to L-asparaginase (P = 0.01, P = 0.0036) than those of the FAB M2 subtype. FAB M5 leukemia was more sensitive to etoposide than were the FAB M2, M4 and M7 subtypes (P = 0.001, P = 0.034, P = 0.023, respectively). By contrast, FAB M5 leukemia was significantly more resistant to prednisolone and dexamethasone than were the FAB M0, M1, M2, M4 and M7 subtypes. We sought correlations between in vitro drug resistance and long-term clinical outcome, but found no associations in this case. These results suggest that in vitro resistance to cytarabine, melphalan, etoposide, L-asparaginase, aclarubicin and dexamethasone might represent factors that can predict response to the early course of therapy. Selecting an appropriate anti-cancer drug according to the FAB classification together with drug sensitivity testing may contribute to improved prognoses in childhood acute myeloid leukemia.

  6. General Information about Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

    Science.gov (United States)

    ... General information about clinical trials is also available. Acute Promyelocytic Leukemia Treatment of acute promyelocytic leukemia may include the ... information about clinical trials is also available. Recurrent Acute Promyelocytic ... of recurrent acute promyelocytic leukemia may include ...

  7. The role of ATP-binding cassette transporter A2 in childhood acute lymphoblastic leukemia multidrug resistance

    OpenAIRE

    Aberuyi, N; S. Rahgozar; Moafi, A

    2014-01-01

    Acute lymphoblastic leukemia (ALL) is one of the most prevalent hematologic malignancies in children. Although the cure rate of ALL has improved over the past decades, the most important reason for ALL treatment failure is multidrug resistance (MDR) phenomenon. The current study aims to explain the mechanisms involved in multidrug resistance of childhood ALL, and introduces ATP-binding cassette transporterA2 (ABCA2) as an ABC transporter gene which may have a high impact on MDR. Benefiting fr...

  8. ATF5 polymorphisms influence ATF function and response to treatment in children with childhood acute lymphoblastic leukemia

    OpenAIRE

    Rousseau, Julie; Gagné, Vincent; Labuda, Malgorzata; Beaubois, Cyrielle; Sinnett, Daniel; Laverdière, Caroline; Moghrabi, Albert; Sallan, Stephen E.; Silverman, Lewis B.; Neuberg, Donna; Kutok, Jeffery L.; Krajinovic, Maja

    2011-01-01

    Asparaginase is a standard and critical component in the therapy of childhood acute lymphoblastic leukemia. Asparagine synthetase (ASNS) and the basic region leucine zipper activating transcription factor 5 (ATF5) and arginosuccinate synthase 1 (ASS1) have been shown to mediate the antileukemic effect of asparaginase and to display variable expression between leukemia cells that are resistant and sensitive to treatment. Fourteen polymorphisms in the regulatory and coding regions of these gene...

  9. MTHFR polymorphisms in childhood acute lymphoblastic leukemia: influence on methotrexate therapy

    Directory of Open Access Journals (Sweden)

    Umerez M

    2017-03-01

    Full Text Available Maitane Umerez,1 Ángela Gutierrez-Camino,1 Carmen Muñoz-Maldonado,1 Idoia Martin-Guerrero,1 Africa Garcia-Orad1,2 1Department of Genetics, Physical Anthropology and Animal Physiology, Faculty of Medicine and Nursery, University of the Basque Country, UPV/EHU, Leioa, 2BioCruces Health Research Institute, Barakaldo, Spain Abstract: Methotrexate (MTX is an important component in the therapy used to treat childhood acute lymphoblastic leukemia (ALL. Methylenetetrahydrofolate reductase (MTHFR is a key enzyme for MTX pharmacokinetics. Two single-nucleotide polymorphisms in MTHFR gene, C677T and A1298C, affecting MTHFR activity, have been widely studied as potential markers of MTX toxicity and/or outcome in pediatric ALL. In this review, we show that the majority of published reports do not find association or present opposite effect. Therefore, MTHFR C677T and A1298C polymorphisms do not seem to be good markers of MTX-related toxicity and/or outcome in pediatric ALL. The efforts should be focused on other genes, such as transporter genes or microRNA-related genes. Keywords: MTHFR, methotrexate, toxicity, outcome, C677T, A1298C

  10. Proteomic changes in a childhood acute lymphoblastic leukemia cell line during the adaptation to vincristine.

    Science.gov (United States)

    Guzmán-Ortiz, Ana Laura; Aparicio-Ozores, Gerardo; Valle-Rios, Ricardo; Medina-Contreras, Oscar; Patiño-López, Genaro; Quezada, Héctor

    Relapse occurs in approximately 20% of Mexican patients with childhood acute lymphoblastic leukemia (ALL). In this group, chemoresistance may be one of the biggest challenges. An overview of complex cellular processes like drug tolerance can be achieved with proteomic studies. The B-lineage pediatric ALL cell line CCRF-SB was gradually exposed to the chemotherapeutic vincristine until proliferation was observed at 6nM, control cells were cultured in the absence of vincristine. The proteome from each group was analyzed by nanoHPLC coupled to an ESI-ion trap mass spectrometer. The identified proteins were grouped into overrepresented functional categories with the PANTHER classification system. We found 135 proteins exclusively expressed in the presence of vincristine. The most represented functional categories were: Toll receptor signaling pathway, Ras Pathway, B and T cell activation, CCKR signaling map, cytokine-mediated signaling pathway, and oxidative phosphorylation. Our study indicates that signal transduction and mitochondrial ATP production are essential during adaptation of leukemic cells to vincristine, these processes represent potential therapeutic targets. Copyright © 2017 Hospital Infantil de México Federico Gómez. Publicado por Masson Doyma México S.A. All rights reserved.

  11. Motor nervous system impairment persists in long-term survivors of childhood acute lymphoblastic leukemia.

    Science.gov (United States)

    Lehtinen, Satu S; Huuskonen, Usko E; Harila-Saari, Arja H; Tolonen, Uolevi; Vainionpää, Leena K; Lanning, B Marjatta

    2002-05-01

    The objective of the current study was to determine whether therapy for childhood acute lymphoblastic leukemia (ALL) results in long-lasting neurologic signs or electrophysiologic injuries within the motor tracts. Twenty-seven children who were treated for ALL were studied clinically 5 years after the cessation of therapy by means of motor-evoked potentials (MEPs) elicited by magnetic stimulation transcranially and peripherally. An equal number of healthy children matched with regard to age, gender, and height served as the control group. The MEP latencies to the hands and legs elicited by stimulation at the cortex were prolonged significantly in the children treated for ALL compared with the control group, with the differences being 2.2 milliseconds [ms] (P motor difficulties and dysdiadochokinesia. Neurologic signs still persisted 5 years after therapy for ALL. Approximately 33% of the patients had fine or gross motor difficulties and dysdiadochokinesia, and demyelinative injuries to the peripheral nerve tracts were found proximally but not within the central nervous system. Copyright 2002 American Cancer Society.DOI 10.1002/cncr.10503

  12. Childhood acute lymphoblastic leukemia in Turkey: factors influencing treatment and outcome: a single center experience.

    Science.gov (United States)

    Hazar, Volkan; Karasu, Gulsun Tezcan; Uygun, Vedat; Akcan, Mediha; Küpesiz, Alphan; Yesilipek, Akif

    2010-11-01

    There is limited data about the long-term treatment outcome and prognosis of childhood acute lymphoblastic leukemia (ALL) in developing countries. Our study was designed to assess survival data and identify risk factors. Data of 142 children with ALL who were treated with a modified BFM 95 protocol between 1997 and 2007 were evaluated. The median age was 4.3 years. Complete remission (CR) rate after induction phase was 93.5%; with 2.1% induction-related mortality and 0.7% having resistance disease. Of complete responders, 67.1% are in continuous CR with a median follow-up of 63 months (range: 24 to 153 mo). Treatment-related mortality was 17.7% and the total rate of treatment abandonment was 3.5%. The probability of event-free survival was 67.3% (95% confidence interval 59.3-75.3) at 4 years and 63.2% (95% confidence interval 54.4-72.0) at 8 years. This report examines children with ALL treated with a modified ALL-BFM 95 protocol in a tertiary care center in Turkey with adequate follow up and demonstrates the need for improvements especially for patients with unfavorable risk group and strategies to reduce deaths from infection in CR to keep pace with cure rates in developed countries.

  13. Childhood acute disseminated encephalomyelitis: the role of brain and spinal cord MRI

    Energy Technology Data Exchange (ETDEWEB)

    Khong, Pek-Lan; Cheng, Pui-Wai; Chan, Fu-Luk [Department of Diagnostic Radiology, University of Hong Kong (Hong Kong); Ho, Hok-Kung; Wong, Virginia C.N.; Goh, Winnie [Department of Paediatrics, University of Hong Kong, Queen Mary Hospital (Hong Kong)

    2002-01-01

    Background. It is recognised that the clinical and radiological spectrum of childhood acute disseminated encephalomyelitis (ADEM) is wide. Objective. To determine whether initial MRI features are predictive of clinical outcome and to determine the role of MRI in the management of ADEM. Materials and methods. The MRI scans of ten consecutive children (eight boys, two girls), clinically and radiologically diagnosed to have ADEM, were retrospectively reviewed. Follow-up MRI was available for eight patients. Results. Lesions ranged from small and punctate (<1 cm) to moderate sized and confluent (4-5 cm) to diffuse and extensive. Spinal cord lesions, seen in five of seven children, were contiguous or segmental. Seven children (70%) made good clinical recovery while three children (30%) remained severely handicapped. There was no correlation between the site, extent and pattern of involvement and clinical outcome. However, the evolution of MRI findings on follow-up correlated well with the subsequent clinical course and outcome. Conclusions. Although the extent and site of lesions on initial MRI scans are not predictive of clinical outcome, early MRI of the brain and spine is useful in aiding clinical diagnosis, and subsequent follow-up MRI is helpful in monitoring disease progression. (orig.)

  14. Trajectories of Obesity and Overweight Rates Among Survivors of Childhood Acute Lymphoblastic Leukemia.

    Science.gov (United States)

    Winkler, Megan R; Hockenberry, Marilyn J; McCarthy, Kathy S; Silva, Susan G

    2015-07-01

    To describe the trajectories of obesity/overweight rates by age group among survivors of childhood acute lymphoblastic leukemia (ALL) from diagnosis through several years post-therapy. Longitudinal, descriptive. Hematology/oncology clinic in the southwestern United States. 62 child and adolescent ALL survivors receiving treatment and follow-up care from 1999-2013. Retrospective chart review of height, weight, and body mass index. Annual obesity/overweight rates and developmental age groups. Different trajectories of obesity/overweight rates existed among age groups. Forty-seven percent of adolescents met the Centers for Disease Control and Prevention criteria for obesity/overweight status at some point following diagnosis, compared to 68% of school-age and 73% of preschool children. Preschool children demonstrated the most rapid rate increase following diagnosis, with a particularly susceptible period in the years immediately following therapy. Obesity/overweight persistence was most characteristic of school-age children. Important variations in rate and pattern of weight status trajectories exist by age group, demonstrating that children diagnosed with ALL during the preschool and school-age developmental years have the greatest vulnerability of developing obesity/overweight status. Obesity/overweight prevention efforts are greatly needed in children with ALL, and efforts should occur before ALL treatment completion in preschool and school-age children.

  15. A systematic review and meta-analysis of the association between childhood infections and the risk of childhood acute lymphoblastic leukaemia.

    Science.gov (United States)

    Hwee, Jeremiah; Tait, Christopher; Sung, Lillian; Kwong, Jeffrey C; Sutradhar, Rinku; Pole, Jason D

    2018-01-01

    To determine whether childhood infections were associated with the development of childhood acute lymphoblastic leukaemia (ALL). We included studies that assessed any infection in childhood prior to the diagnosis of ALL in children aged 0-19 years compared to children without cancer. The primary analysis synthesised any infection against the odds of ALL, and secondary analyses assessed the frequency, severity, timing of infections, and specific infectious agents against the odds of ALL. Subgroup analyses by data source were investigated. In our primary analysis of 12 496 children with ALL and 2 356 288 children without ALL from 38 studies, we found that any infection was not associated with ALL (odds ratio (OR)=1.10, 95% CI: 0.95-1.28). Among studies with laboratory-confirmed infections, the presence of infections increased the odds of ALL by 2.4-fold (OR=2.42, 95% CI: 1.54-3.82). Frequency, severity, and timing of infection were not associated with ALL. The hypothesis put forward by Greaves and others about an infectious aetiology are neither confirmed nor refuted and the overall evidence remains inadequate for good judgement. The qualitative difference in the subgroup effects require further study, and future research will need to address the challenges in measuring infectious exposures.

  16. Analysis of p16 gene mutations and deletions in childhood acute lymphoblastic leukemias

    Directory of Open Access Journals (Sweden)

    José Alexandre Rodrigues Lemos

    Full Text Available CONTEXT: The p16 tumor suppressor gene encodes a cyclin-dependent kinase 4 inhibitor that blocks cell division during the G1 phase of the cell cycle. Alterations in this gene have been reported for various neoplasia types, including acute lymphoblastic leukemias (ALL, especially T-cell acute lymphoblastic leukemias (ALL. OBJECTIVE: To determine probable alterations in the p16 gene in children with acute lymphoblastic leukemias using the polymerase chain reaction (PCR and direct DNA sequencing and also to analyze event-free survival (EFS. DESIGN: Retrospective study. SETTING: Department of Child Care and Pediatrics, Faculty of Medicine of Ribeirão Preto, Universidade Federal de São Paulo. PARTICIPANTS: Fifty-six children with ALL (mean age 4 years. Forty (71.43% had B-cell and 12 (21.43% had T-cell ALL; 4 (7.1% were biphenotypic. SAMPLE: DNA samples were extracted from bone marrow upon diagnosis and/or relapse. In 2 T-cell cases, DNA from cerebrospinal fluid (CSF was analyzed. MAIN MEASUREMENTS: Deletions or nucleotide substitutions in exons 1, 2 and 3 of the p16 gene were determined by PCR and nucleotide sequencing. Event-free survival was determined by the Kaplan-Meyer and log-rank test for patients carrying normal and altered p16. RESULTS: Deletions in exon 3 were observed in five cases. Abnormal migration in PCR was observed in seven cases for exon 1, six for exon 2, and five for exon 3. Mutations in exon 1 were confirmed by direct DNA sequencing in four cases and in exon 2 in two cases. The Kaplan-Meyer survival curves and the log-rank test showed no significant differences in 5-year EFS between children with normal or altered p16, or between patients with B-ALL carrying normal or altered p16 gene. Patients with T-ALL could not be evaluated via Kaplan-Meier due to the small number of cases. CONCLUSIONS: Our results, particularly regarding deletion frequency, agree with others suggesting that deletions in the p16 are initial events in

  17. Epidemiology of childhood Guillain-Barré syndrome as a cause of acute flaccid paralysis in Honduras: 1989-1999.

    Science.gov (United States)

    Molinero, Marco R; Varon, Daniel; Holden, Kenton R; Sladky, John T; Molina, Ida B; Cleaves, Francisco

    2003-11-01

    The objective of this study was to investigate the incidence of acute flaccid paralysis in the pediatric population of Honduras over an 11-year period, determine what percentage of acute flaccid paralysis was Guillain-Barré syndrome, and identify the epidemiologic features of Guillain-Barré syndrome. There were 546 childhood cases of acute flaccid paralysis seen between January 1989 and December 1999 at the Hospital Escuela Materno-Infantil in Tegucigalpa, Honduras. Of these cases with acute flaccid paralysis, 394 (72.2%) were diagnosed with Guillain-Barré syndrome. Our incidence of Guillain-Barré syndrome in the Honduran pediatric population (1.37/100,000 per year) is higher than that shown in other studies. There was a significantly higher incidence of Guillain-Barré syndrome in younger children (ages 1-4 years), a significant preponderance of cases from rural areas, and a mild predominance in boys but a typical clinical presentation. The Honduran pediatric Guillain-Barré syndrome population had an increased mortality rate. Guillain-Barré syndrome has become the leading cause of childhood paralysis in Honduras. A better understanding of the population at highest risk and opportunities for earlier intervention with more effective therapeutic modalities may permit reducing the mortality among Honduran children who develop Guillain-Barré syndrome.

  18. Recurrent focal myositis in a patient on maintenance hemodialysis

    Directory of Open Access Journals (Sweden)

    Manjusha Yadla

    2015-04-01

    Full Text Available Focal myositis is a benign inflammatory process involving a single group of muscles. It may resolve with conservative measures or may be a harbinger for polymyositis. Very few focal myosites are recurrent, and recurrence in patients with end-stage renal disease on hemodialysis is extremely rare. Clinical examination, electromyography, and magnetic resonance imaging help in identifying this entity. Muscle biopsy and histopathological evaluation are mandatory in diagnosis. It often responds to conservative treatment with anti-inflammatory drugs and physiotherapy, but occasionally it requires therapy with steroids.

  19. Non-traumatic myositis ossificans circumscripta: A diagnosis trap

    OpenAIRE

    El Bardouni, Ahmed; Boufettal, Monsef; Zouaidia, Fouad; Kharmaz, Mohamed; Berrada, Mohamed S.; Mahassini, Najat; El Yaacoubi, Moradh

    2014-01-01

    Myositis ossificans circumscripta (MOC) is a benign condition of non-neoplastic heterotopic bone formation in the muscle or soft tissue. Trauma plays a role in the development of MOC, thus, non-traumatic MOC is very rare. Although MOC may occur anywhere in the body, the lesions are localized predominantly in the high-risk sites of injury, such as the thigh, buttock, and elbow. MOC can easily be mistaken for osteomyelitis or a malignant tumor, specifically osteosarcoma or soft-tissue sarcoma. ...

  20. Inclusion-Body Myositis Associated with Alzheimer’s Disease

    Directory of Open Access Journals (Sweden)

    Danijela Levacic

    2013-01-01

    Full Text Available Sporadic inclusion-body myositis (s-IBM is a myopathy that is characterized by progressive weakness and muscle pathology demonstrating inflammation and rimmed vacuoles. In addition, similar to the pathology observed in the brains of patients with Alzheimer’s disease, the deposition of beta-amyloid and phosphorylated tau proteins in muscle fibers has been reported. These shared pathologic features have prompted hypotheses suggesting a shared etiology of these two conditions. We report a case of a 73-year-old woman initially diagnosed with s-IBM who later developed Alzheimer’s disease.

  1. The metabolic syndrome in survivors of childhood acute lymphoblastic leukemia in Isfahan, Iran

    Directory of Open Access Journals (Sweden)

    Nahid Reisi

    2009-04-01

    Full Text Available

    • BACKGROUND: To determine the prevalence of metabolic syndrome in survivors of childhood leukemia in Isfahan, Iran.
    • METHODS: During a 4-year period (2003 to 2007, 55 children (33 male and 22 female diagnosed with ALL at Unit of Hematology/ Oncology, Department of Pediatrics, Isfahan University of Medical Science, were enrolled in this crosssectional study. Metabolic syndrome was defined using the modified version of Adult Treatment Panel (ATP III criteria. Insulin resistance was defined based on the homeostasis model assessment index (HOMA-IR.
    • RESULTS: The mean age of participates was 10.4 years (range 6-19 years and the mean interval since completion of chemotherapy was 35 months. Twenty percent (11/55 of survivors (10 male, 1 female met criteria for diagnosis of metabolic syndrome. Obesity was observed in one forth of patients and nearly 3/4 of obese patients had metabolic syndrome. High serum insulin levels were found in 16% of participants and in 63% of obese survivors. The mean insulin levels in survivors with metabolic syndrome was three-times more than those without (28.3 mu/l vs. 9.57 mu/l, p = 0.004. Insulin resistance was detected in 72.7% of survivors with metabolic syndrome and it was  ositively correlated with serum triglycerides (0.543, p < 0.001, systolic and diastolic BP (0.348, p = 0.01 and 0.368, p = 006 respectively, insulin levels (0.914, p < 0.001 and blood sugar (0.398, p = 003.
    • CONCLUSIONS: The prevalence of metabolic syndrome in survivors of childhood leukemia in Iran is higher than developed countries. Nearly all of the obese patients had metabolic syndrome. Weight control and regular physical exercise are recommended to the survivors.
    • KEYWORDS: Acute lymphoblastic leukemia, metabolic syndrome, obesity, children.

  2. HLA complex-linked heat shock protein genes and childhood acute lymphoblastic leukemia susceptibility.

    Science.gov (United States)

    Ucisik-Akkaya, Esma; Davis, Charronne F; Gorodezky, Clara; Alaez, Carmen; Dorak, M Tevfik

    2010-09-01

    Three heat shock protein 70 (HSP70) genes, HSPA1L, HSPA1A, and HSPA1B, are located within the human leukocyte antigen (HLA) class III region. HSPs act as stress signals and regulate natural killer cell response to cancer. HSP70 gene polymorphisms show disease associations partly due to their linkage disequilibrium with HLA alleles. To systematically evaluate their associations with childhood acute lymphoblastic leukemia (ALL), we examined the three functional single nucleotide polymorphisms (SNPs) rs2227956 (T493M) in HSPA1L, rs1043618 in HSPA1A 5'UTR, and rs1061581 (Q351Q) in HSPA1B by TaqMan assays or polymerase chain reaction-restriction fragment length polymorphism in 114 ALL cases and 414 controls from Wales (UK), in 100 Mexican Mestizo ALL cases and 253 controls belonging to the same ethnic group, and in a panel of 82 HLA-typed reference cell line samples. Homozygosity for HSPA1B rs1061581 minor allele G was associated with protection (odds ratio (OR) = 0.37, 95% confidence interval (CI) = 0.16-0.78; P = 0.007) with gene-dosage effect (additive model) reaching significance (P = 0.0001) in the Welsh case-control group. This association was replicated in the second case-control group from Mexico (OR (recessive model) = 0.49, 95% CI = 0.24-0.96; P = 0.03), and the pooled analysis yielded a strong association (Mantel-Haenszel OR = 0.43, 95% CI = 0.27-0.69, P = 0.0004). The association was stronger in males in each group and in the pooled analysis. A three-SNP haplotype including the major allele A of rs1061581 showed a highly significant increase in Welsh cases compared with respective controls (6.7% vs 1.8%; P = 0.0003) due to the difference between male cases and controls. The protective allele of rs1061581 occurred more frequently on the HLA-DRB3 haplotypes (especially DRB1*03) in the cell line panel, but the HSPA1B association was independent from the HLA-DRB4 association previously detected in the same case-control group from Wales (adjusted P = 0

  3. Idiopathic Inflammatory Myopathies; Association with Overlap Myositis and Syndromes: Classification, Clinical Characteristics, and Associated Autoantibodies

    Directory of Open Access Journals (Sweden)

    Pari Basharat

    2016-07-01

    Full Text Available Idiopathic inflammatory myopathies (IIM are traditionally identified as a group of disorders that target skeletal muscle due to autoimmune dysfunction. The IIM can be divided into subtypes based on certain clinical characteristics, and several classification schemes have been proposed. The predominant diagnostic criteria for IIM is the Bohan and Peter criteria, which subdivides IIM into primary polymyositis (PM, primary dermatomyositis (DM, myositis with another connective tissue disease, and myositis associated with cancer. However, this measure has been criticised for several reasons including lack of specific criteria to help distinguish between muscle biopsy findings of PM, DM, and immune-mediated necrotising myopathy, as well as the lack of identification of cases of overlap myositis (OM. Because of this issue, other classification criteria for IIM have been proposed, which include utilising myositis-associated antibodies and myositis-specific antibodies, as well as overlap features such as Raynaud’s phenomenon, polyarthritis, oesophageal abnormalities, interstitial lung disease, small bowel abnormalities such as hypomotility and malabsorption, and renal crises, amongst others. Indeed, the identification of autoantibodies associated with certain clinical phenotypes of myositis, in particular connective tissue disease-myositis overlap, has further helped divide IIM into distinct clinical subsets, which include OM and overlap syndromes (OS. This paper reviews the concepts of OM and OS as they pertain to IIM, including definitions in the literature, clinical characteristics, and overlap autoantibodies.

  4. Physical function and muscle strength in sporadic inclusion body myositis

    DEFF Research Database (Denmark)

    Jørgensen, Anders N; Aagaard, Per; Nielsen, Jakob L

    2017-01-01

    INTRODUCTION: In this study, self-reported physical function, functional capacity, and isolated muscle function were investigated in sporadic inclusion body myositis (sIBM) patients. METHODS: The 36-item Short Form (SF-36) Health Survey and 2-min walk test (2MWT), timed up & go test (TUG), and 30...... to sensitively predict self-perceived physical function in sIBM patients. Notably, between-limb asymmetry in lower limb muscle strength had a substantial negative impact on motor tasks involving gait function. Muscle Nerve, 2017.......INTRODUCTION: In this study, self-reported physical function, functional capacity, and isolated muscle function were investigated in sporadic inclusion body myositis (sIBM) patients. METHODS: The 36-item Short Form (SF-36) Health Survey and 2-min walk test (2MWT), timed up & go test (TUG), and 30-s...... chair stand performance were evaluated. In addition, patients were tested for knee extensor muscle strength (isokinetic dynamometer) and leg extension power (Nottingham power rig). RESULTS: TUG performance was the strongest predictor of self-reported physical function (r(2) = 0.56, P

  5. The contribution of ultrasonography and sonoelastography in assessment of myositis.

    Science.gov (United States)

    Botar-Jid, Carolina; Damian, Laura; Dudea, Sorin M; Vasilescu, Dan; Rednic, Simona; Badea, Radu

    2010-06-01

    To analyze the utility of ultrasonography (US) in the assessment of inflammatory myopathies, and of sonoelastography in the assessment of the elasticity of skeletal muscle in myositis. The study group comprised 24 patients with musculoskeletal pathology examined using Hitachi 8500 EUB equipment with a 6.5-13 MHz transducer and software for elastography. The images were analyzed in conjunction with clinical and biochemical data. Using dedicated software for color information from the elastographic images, the average values for color intensity, hue and dispersion were calculated. After the correlation of US images with clinical and paraclinical data the highest average values for color parameters were encountered on the superior third of the thigh. There was a proportional concordance between the average values of the color parameters and serum creatine kinase and serum lactic dehydrogenase and there was no significant agreement between the average values of the color parameters and the erythrocyte sedimentation rate, positive rheumatoid factor or positive antinuclear antibody. The correlation between the quantitative colour parameters from the elastographic images and the laboratory studies suggest that sonoelastography could be an important tool in the management of the patients with myositis.

  6. The role of KIR genes and their cognate HLA class I ligands in childhood acute lymphoblastic leukemia.

    Science.gov (United States)

    de Smith, Adam J; Walsh, Kyle M; Ladner, Martha B; Zhang, Siming; Xiao, Carmen; Cohen, Franziska; Moore, Theodore B; Chokkalingam, Anand P; Metayer, Catherine; Buffler, Patricia A; Trachtenberg, Elizabeth A; Wiemels, Joseph L

    2014-04-17

    Killer cell immunoglobulin-like receptors (KIRs), via interaction with their cognate HLA class I ligands, play a crucial role in the development and activity of natural killer cells. Following recent reports of KIR gene associations in childhood acute lymphoblastic leukemia (ALL), we present a more in-depth investigation of KIR genes and their cognate HLA ligands on childhood ALL risk. Genotyping of 16 KIR genes, along with HLA class I groups C1/C2 and Bw4 supertype ligands, was carried out in 212 childhood ALL cases and 231 healthy controls. Frequencies of KIR genes, KIR haplotypes, and combinations of KIR-HLA ligands were tested for disease association using logistic regression analyses. KIR A/A genotype frequency was significantly increased in cases (33.5%) compared with controls (24.2%) (odds ratio [OR] = 1.57; 95% confidence interval [CI], 1.04-2.39). Stratifying analysis by ethnicity, a significant difference in KIR genotype frequency was demonstrated in Hispanic cases (34.2%) compared with controls (21.9%) (OR = 1.86; 95% CI, 1.05-3.31). Homozygosity for the HLA-Bw4 allele was strongly associated with increased ALL risk exclusively in non-Hispanic white children (OR = 3.93; 95% CI, 1.44-12.64). Our findings suggest a role for KIR genes and their HLA ligands in childhood ALL etiology that may vary among ethnic groups.

  7. Nutritional intake of long-term survivors of childhood acute lymphoblastic leukemia: evidence for bone health interventional opportunities.

    Science.gov (United States)

    Tylavsky, Frances A; Smith, Karen; Surprise, Harriet; Garland, Sarah; Yan, Xiaowei; McCammon, Elizabeth; Hudson, Melissa M; Pui, Ching-Hon; Kaste, Sue C

    2010-12-15

    Survivors of childhood acute lymphoblastic leukemia (ALL) are vulnerable to exaggeration of the aging process including decreased bone mineral density (BMD). As little is known about their dietary or nutrient intake that may affect their long-term bone health, we examined nutrient intake in long-term survivors of childhood ALL. Survivors (n = 164) of childhood ALL who had completed treatment for at least 5 years and were in continuous remission, completed a 110-item food questionnaire that reflected dietary intake over the previous year. The analyzed cohort comprised 34 females and 38 males younger than 19 years and 45 females and 47 males at least 19 years. Reported nutrient intake and food selection were compared with age-specific Recommended Dietary Allowance and USDA Pyramid Food Guide. Body mass index was compared to the general US population, adjusted for age, gender, Tanner stage and race. Less than 30% of participants met recommended dietary intakes for vitamin D, calcium, potassium, or magnesium regardless of age. Mean daily caloric intake was 2,204 kcal (51% from carbohydrates) for younger and 2,160 kcal (49% from carbohydrates) for older participants. Energy intake from sweets was 70% higher than recommended. Participants 19 years more likely to be overweight (odds ratio 1.95, 95% CI 1.11-3.32, P < 0.002). Survivors of childhood ALL need careful dietary intervention to optimize long-term health.

  8. A task-based assessment of parental occupational exposure to pesticides and childhood acute lymphoblastic leukemia.

    Science.gov (United States)

    Gunier, Robert B; Kang, Alice; Hammond, S Katharine; Reinier, Kyndaron; Lea, C Suzanne; Chang, Jeffrey S; Does, Monique; Scelo, Ghislaine; Kirsch, Janice; Crouse, Vonda; Cooper, Robert; Quinlan, Patricia; Metayer, Catherine

    2017-07-01

    Associations between parental occupational pesticide exposure and childhood acute lymphoblastic leukemia (ALL) vary across studies, likely due to different exposure assessment methodologies. We assessed parental occupational pesticide exposure from the year before pregnancy to the child's third year of life for 669 children diagnosed with ALL and 1021 controls. We conducted expert rating using task-based job modules (JM) to estimate exposure to pesticides among farmer workers, gardeners, agricultural packers, and pesticide applicators. We compared this method to (1) partial JM using job titles and a brief description, but without completing the task-based questionnaire, and (2) job exposure matrix (JEM) linking job titles to the International Standard Classifications of Occupation Codes. We used unconditional logistic regression to calculate odds ratios (OR) and 95% confidence intervals (95% CI) for ALL cancer risk and pesticide exposure adjusting for child's sex, age, race/ethnicity and household income. Compared to complete JMs, partial JMs and JEM led to 3.1% and 9.4% of parents with pesticide exposure misclassified, respectively. Misclassification was similar in cases and controls. Using complete JMs, we observed an increased risk of ALL for paternal occupational exposure to any pesticides (OR=1.7; 95% CI=1.2, 2.5), with higher risks reported for pesticides to treat nut crops (OR=4.5; 95% CI=0.9, 23.0), and for children diagnosed before five years of age (OR=2.3; 95% CI: 1.3, 4.1). Exposure misclassification from JEM attenuated these associations by about 57%. Maternal occupational pesticide exposure before and after birth was not associated with ALL. The risk of ALL was elevated in young children with paternal occupational pesticide exposure during the perinatal period, using more detailed occupational information for exposure classification. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Analysis of Normal Hematopoietic Stem and Progenitor Cell Contents in Childhood Acute Leukemia Bone Marrow.

    Science.gov (United States)

    Balandrán, Juan Carlos; Vadillo, Eduardo; Dozal, David; Reyes-López, Alfonso; Sandoval-Cabrera, Antonio; Laffont-Ortiz, Merle Denisse; Prieto-Chávez, Jessica L; Vilchis-Ordoñez, Armando; Quintela-Nuñez Del Prado, Henry; Mayani, Héctor; Núñez-Enríquez, Juan Carlos; Mejía-Aranguré, Juan Manuel; López-Martínez, Briceida; Jiménez-Hernández, Elva; Pelayo, Rosana

    2016-11-01

    Childhood acute leukemias (AL) are characterized by the excessive production of malignant precursor cells at the expense of effective blood cell development. The dominance of leukemic cells over normal progenitors may result in either direct suppression of functional hematopoiesis or remodeling of microenvironmental niches, contributing to BM failure and AL-associated mortality. We undertook this study to investigate the contents and functional activity of hematopoietic stem/progenitor cells (HSPC) and their relationship to immune cell production and risk status in AL pediatric patients. Multiparametric flow cytometry of BM aspirates was performed to classify AL on the basis of lineage and differentiation stages and to analyze HSPC and immune cell frequencies. Controlled co-culture systems were conducted to evaluate functional lineage potentials of primitive cells. Statistical correlations and inter-group significant differences were established. Among 113 AL BM aspirates, 26.5% corresponded to ProB, 19.5% to PreB and 32% contain ProB and PreB differentiation stages, whereas nearly 9% of the cases were T- and 13% myeloid-lineage leukemias. We identified ProB-ALL as the subtype endowed with the highest relative contents of HSPC, whereas T-ALL and PreB-ALL showed a critically reduced size of both HSC and MLP compartments. Notably, lower cell frequencies of HSPC in ProB-ALL correlated to high-risk prognosis at disease debut. HSPC abundance at initial diagnosis may aid to predict the clinical course of ALL and to identify high-risk patients. A clearer understanding of their population dynamics and functional properties in the leukemia setting will potentially pave the way for targeted therapies. Copyright © 2016 IMSS. Published by Elsevier Inc. All rights reserved.

  10. Oral purified bacterial extracts in acute respiratory tract infections in childhood: a systematic quantitative review.

    Science.gov (United States)

    Steurer-Stey, Claudia; Lagler, Leonie; Straub, Daniel A; Steurer, Johann; Bachmann, Lucas M

    2007-04-01

    Recurrent acute respiratory tract infections (ARTI) are a common problem in childhood. Some evidence suggests a benefit regarding the prevention of ARTI in children treated with the immunomodulator OM-85 BV (Bronchovaxom). We summarised the evidence on the effectiveness of the immunomodulator OM-85 BV in the prevention of ARTI in children. We searched randomised comparisons of oral purified bacterial extracts against inactive controls in children with respiratory tract diseases in nine electronic databases and reference lists of included studies. We extracted salient features of each study, calculated relative risks (RR) or weighted mean differences (WMD) and performed meta-analyses using random-effects models. Thirteen studies (2,721 patients) of low to moderate quality tested OM-85 BV. Patients and outcomes differed substantially, which impeded pooling results of more than two trials. Two studies (240 patients) reporting on the number of patients with less than three infections over 6 month of follow-up in children not in day care showed a trend for benefit RR 0.82 (95% CI, 0.65-1.02). One out of two studies examining the number of children not in day care without infections over 4-6 month reported a significant RR of 0.42 (95% CI, 0.21-0.82) whereas the smaller, second study did not [RR 0.92 (95% CI, 0.58-1.46)]. Two studies reporting the number of antibiotic courses indicated a benefit for the intervention arm [WMD 2.0 (95% CI, 1.7-2.3)]. Two out of the three studies showed a reduction of length of episodes of 4-6 days whereas a third study showed no difference between the two groups. Evidence in favour of OM-85 BV in the prevention of ARTI in children is weak. There is a trend for fewer and shorter infections and a reduction of antibiotic use.

  11. Endocrinological and Cardiological Late Effects Among Survivors of Childhood Acute Lymphoblastic Leukemia

    Directory of Open Access Journals (Sweden)

    Hale Ören

    2013-09-01

    Full Text Available Objective: Survival rates for childhood acute lymphoblastic leukemia (ALL have significantly improved and late effects of therapy have been important in the follow-up of survivors. The objective of this study is to identify the endocrinological and cardiological late effects of ALL patients treated in our pediatric hematology unit. Materials and Methods: Patients treated for ALL with BFM protocols after at least 5 years of diagnosis and not relapsed were included in the study. Endocrinological late effects (growth failure, obesity, insulin resistance, dyslipidemia, thyroid gland disorders, osteopenia/osteoporosis, and pubertal disorders and cardiological late effects were evaluated. The study group was evaluated with anthropometric measurements, body mass index, and laboratory testing of fasting glucose, insulin, serum lipids, thyroid functions, and bone mineral densities. Echocardiography and pulsed wave Doppler imaging were performed for analysis of cardiac functions. Results: Of the 38 ALL survivors, at least 1 adverse event occurred in 23 (60%, with 8 of them (21% having multiple problems. Six (16% of the survivors were obese and 8 (21% of them were overweight. Subjects who were overweight or obese at the time of diagnosis were more likely to be overweight or obese at last follow-up. Obesity was more frequently determined in patients who were younger than 6 years of age at the time of diagnosis. Insulin resistance was observed in 8 (21% subjects. Insulin resistance was more frequently seen in subjects who had family history of type 2 diabetes mellitus. Hyperlipidemia was detected in 8 (21% patients. Hypothyroidism or premature thelarche were detected in 2 children. Two survivors had osteopenia. Cardiovascular abnormalities occurred in one of the subjects with hypertension and cardiac diastolic dysfunction. Conclusion: We point out the necessity of follow-up of these patients for endocrinological and cardiological late effects, since at least

  12. Vitamin D status and hospitalisation for childhood acute lower respiratory tract infections in Nigeria.

    Science.gov (United States)

    Ahmed, Patience; Babaniyi, I B; Yusuf, K K; Dodd, Caitlin; Langdon, Gretchen; Steinhoff, Mark; Dawodu, Adekunle

    2015-05-01

    Acute lower respiratory tract infection (ALRTI) is the leading cause of childhood deaths in most developing countries, including Nigeria. Vitamin D is associated with innate immunity and may play a role in the control of infections. Case-control studies, including a small study from Nigeria, show inconsistent results for the association between vitamin D status and risk of ALRTI. To examine the relationship between vitamin D status and hospitalization for ALRTI in Nigerian children. Fifty children aged 2-60 months hospitalised with ALRTI were studied prospectively. ALRTI was diagnosed on the basis of modified WHO criteria. Each patient was matched with controls for age and gender. The controls were enrolled either from children attending well-child clinics or general clinics without evidence of respiratory infection or admitted to the hospital for elective surgery. A structured questionnaire collected data on demography, health, diet, duration of exposure to sunlight and percentage of body surface exposed to sunlight (according to type of clothing) while outdoors, and potential risk factors for ALRTI. Serum 25-hydroxyvitamin D [25(OH)D] concentration was measured using a chemiluminescenceimmuno-assay. The differences between cases and controls in serum 25(OH)D concentrations, association between vitamin D status and ALRTI and risk factors for vitamin D deficiency were assessed. Mean (SD) 25(OH)D concentrations in patients and controls were similar [61·5 (25·8) vs 63·1 (22·9) nmol/L,P = 0·95].25% of all 100 subjects studied had serum 25(OH)Dvitamin D supplement use (P = 0·009) were independent determinants of vitamin D deficiency in the overall study population. ALRTI was not associated with vitamin D status, but was associated with less exposure to sunlight. Exposure to sunlight and vitamin D supplementation contributed to vitamin D status in this population.

  13. Atypical masticatory muscle myositis in three cavalier King Charles spaniel littermates.

    Science.gov (United States)

    Pitcher, G D C; Hahn, C N

    2007-04-01

    This case report describes a novel manifestation of the immune-mediated disease, masticatory muscle myositis. Clinical signs, including difficulty in opening the mouth (trismus), were seen in three of four 12-week-old cavalier King Charles spaniel littermates. Diagnosis was established by 2M immunohistochemistry, supported by characteristic histopathological changes in affected temporal muscle. Treatment using corticosteroids at immune-modifying doses resulted in resolution of clinical signs in all the affected animals. Masticatory muscle myositis should be considered as a differential diagnosis in groups of young dogs with clinical signs of myositis localised to the head.

  14. DNA methylation for subtype classification and prediction of treatment outcome in patients with childhood acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Milani, Lili; Lundmark, Anders; Kiialainen, Anna

    2010-01-01

    Despite improvements in the prognosis of childhood acute lymphoblastic leukemia (ALL), subgroups of patients would benefit from alternative treatment approaches. Our aim was to identify genes with DNA methylation profiles that could identify such groups. We determined the methylation levels of 1320...... CpG sites in regulatory regions of 416 genes in cells from 401 children diagnosed with ALL. Hierarchical clustering of 300 CpG sites distinguished between T-lineage ALL and B-cell precursor (BCP) ALL and between the main cytogenetic subtypes of BCP ALL. It also stratified patients with high...

  15. Shingles as the underlying cause of orbital myositis in an adolescent: A case report

    Directory of Open Access Journals (Sweden)

    Christopher D. Conrady

    2017-04-01

    Conclusions and importance: In conclusion, orbital myositis is an extremely rare complication of facial VZV infections. Our case highlights the importance of prompt detection and treatment in the pediatric population.

  16. Acute neurocognitive response to methylphenidate among survivors of childhood cancer: a randomized, double-blind, cross-over trial.

    Science.gov (United States)

    Conklin, Heather M; Khan, Raja B; Reddick, Wilburn E; Helton, Susan; Brown, Ronald; Howard, Scott C; Bonner, Melanie; Christensen, Robbin; Wu, Shengjie; Xiong, Xiaoping; Mulhern, Raymond K

    2007-10-01

    To investigate the acute efficacy and adverse side effects of methylphenidate (MPH) among survivors of childhood cancer [acute lymphoblastic leukemia (ALL) or brain tumor (BT)] with learning impairments. Participants (N = 122) completed a two-day, in-clinic, double-blind, cross-over trial during which they received MPH (0.60 mg/kg of body weight) and placebo that were randomized in administration order across participants. Performance was evaluated using measures of attention, memory, and academic achievement. A significant MPH versus placebo effect was revealed on a measure of attention, cognitive flexibility, and processing speed (Stroop Word-Color Association Test). Male gender, older age at treatment, and higher intelligence were predictive of better medication response. No significant differences were found for number or severity of adverse side effects as a function of active medication. MPH shows some neurocognitive benefit and is well tolerated by the majority of children surviving ALL and BT.

  17. Myositis complicating benzathine penicillin-G injection in a case of rheumatic heart disease

    Directory of Open Access Journals (Sweden)

    Joshua R. Francis

    2016-01-01

    Full Text Available A 7-year old boy developed myositis secondary to intramuscular injection of benzathine penicillin-G in the context of secondary prophylaxis for rheumatic heart disease. Side effects of intramuscular delivery of benzathine penicillin-G are well described and include injection site pain and inflammation, but myositis, as depicted on magnetic resonance imaging in this case, has not previously been described.

  18. Atypical proliferative myositis: original MR description with pathologic correlation: Case report

    Energy Technology Data Exchange (ETDEWEB)

    Jarraya, Mohamed; Guermazi, Ali [Boston University School of Medicine, Department of Radiology, Musculoskeletal Section, Boston, MA (United States); Parva, Pedram [VA Boston Healthcare System, Boston, MA (United States); Stone, Michael [Stamford Hospital, Department of Surgery, Stamford, CT (United States); Klein, Michael J. [Hospital for Special Surgery, Department of Pathology and Laboratory Medicine, New York, NY (United States)

    2014-08-15

    Proliferative myositis (PM) along with proliferative fasciitis and nodular fasciitis are a group of pseudosarcomatous myofibroblastic proliferations. Although the histologic presentation of each is almost identical, the magnetic resonance imaging (MRI) appearance of proliferative myositis is closer to that of inflammatory myopathies. We report a case of PM in which the imaging and histologic features combine typical findings of PM with unusual imaging features, suggesting of reactive (or nodular) fasciitis. (orig.)

  19. Minimal Residual Disease Evaluation in Childhood Acute Lymphoblastic Leukemia: An Economic Analysis

    Science.gov (United States)

    Gajic-Veljanoski, O.; Pham, B.; Pechlivanoglou, P.; Krahn, M.; Higgins, Caroline; Bielecki, Joanna

    2016-01-01

    Background Minimal residual disease (MRD) testing by higher performance techniques such as flow cytometry and polymerase chain reaction (PCR) can be used to detect the proportion of remaining leukemic cells in bone marrow or peripheral blood during and after the first phases of chemotherapy in children with acute lymphoblastic leukemia (ALL). The results of MRD testing are used to reclassify these patients and guide changes in treatment according to their future risk of relapse. We conducted a systematic review of the economic literature, cost-effectiveness analysis, and budget-impact analysis to ascertain the cost-effectiveness and economic impact of MRD testing by flow cytometry for management of childhood precursor B-cell ALL in Ontario. Methods A systematic literature search (1998–2014) identified studies that examined the incremental cost-effectiveness of MRD testing by either flow cytometry or PCR. We developed a lifetime state-transition (Markov) microsimulation model to quantify the cost-effectiveness of MRD testing followed by risk-directed therapy to no MRD testing and to estimate its marginal effect on health outcomes and on costs. Model input parameters were based on the literature, expert opinion, and data from the Pediatric Oncology Group of Ontario Networked Information System. Using predictions from our Markov model, we estimated the 1-year cost burden of MRD testing versus no testing and forecasted its economic impact over 3 and 5 years. Results In a base-case cost-effectiveness analysis, compared with no testing, MRD testing by flow cytometry at the end of induction and consolidation was associated with an increased discounted survival of 0.0958 quality-adjusted life-years (QALYs) and increased discounted costs of $4,180, yielding an incremental cost-effectiveness ratio (ICER) of $43,613/QALY gained. After accounting for parameter uncertainty, incremental cost-effectiveness of MRD testing was associated with an ICER of $50,249/QALY gained. In

  20. Isolated left upper extremity myositis and severe rhabdomyolysis in an adult with H1N1 Influenza, a case report with literature review

    Directory of Open Access Journals (Sweden)

    Abhinav Agrawal

    2014-01-01

    Full Text Available Acute viral myositis is a fairly rare condition and usually seen in recovery phase of illness, especially in pediatric or geriatric population. Influenza type A, specifically H1N1 may present with generalized myositis and mild elevation of creatinine kinase in addition to usual manifestations. We would like to discuss an atypical presentation of Type A Influenza (H1N1 in a middle aged male who was never immunized for influenza, presenting with fever, vomiting, anuria and acute severe left upper extremity pain. The most interesting presentation in our patient was that, it was limited to a single extremity, unlike generalized presentation, which was previously reported, acute renal failure warranting renal replacement therapy. This case serves as a reminder for clinicians about atypical manifestations of H1N1 and its threatening metabolic complications. Hence the practitioners should be aware of this rare but possible presentation of certain strains of influenza virus. It also accentuates the importance of being immunized, reminding us of the Old but Golden Adage “Prevention is better than Cure.”

  1. Simultaneous Combined Myositis, Inflammatory Polyneuropathy, and Overlap Myasthenic Syndrome

    Directory of Open Access Journals (Sweden)

    Stéphane Mathis

    2016-01-01

    Full Text Available Immune-mediated neuromuscular disorders include pathologies of the peripheral nervous system, neuromuscular junction, and muscles. If overlap syndromes (or the association of almost two autoimmune disorders are recognized, the simultaneous occurrence of several autoimmune neuromuscular disorders is rare. We describe two patients presenting the simultaneous occurrence of inflammatory neuropathy, myositis, and myasthenia gravis (with positive acetylcholine receptor antibodies. For each patient, we carried out a pathological analysis (nerve and muscle and an electrophysiological study (and follow-up. To our knowledge, this is the first description of such a triple immune-mediated neuromuscular syndrome. We compared our observations with a few other cases of simultaneous diagnosis of two inflammatory neuromuscular disorders.

  2. Inclusion-body myositis presenting with facial diplegia.

    Science.gov (United States)

    Ghosh, Partha S; Laughlin, Ruple S; Engel, Andrew G

    2014-02-01

    The hallmark clinical presentation of inclusion-body myositis (IBM) is slowly progressive weakness that characteristically affects the quadriceps and finger and wrist finger flexor muscles. Facial weakness can also occur, but it is typically mild and not a prominent finding. We describe the clinical features, laboratory investigations, and muscle biopsy findings in a 58-year old man who presented with a 6-year history of marked progressive symmetrical facial weakness. Examination also showed shoulder abduction and hip extensor weakness. The patient's serum creatine kinase level was 655 U/L, and electromyography showed fibrillation potentials and myopathic motor unit potentials. A biopsy specimen of the left biceps muscle was pathognomonic for IBM. This patient did not have a typical presentation for IBM but rather fulfilled the pathological criteria for IBM. To our knowledge, facial diplegia has not been reported previously as a presenting manifestation of IBM. Copyright © 2013 Wiley Periodicals, Inc.

  3. Functional impairment in patients with sporadic Inclusion Body Myositis.

    Science.gov (United States)

    Dunlap, Heather V; Macneil, Lauren G; Tarnopolsky, Mark A

    2014-03-01

    We conducted a retrospective chart review of 53 patients diagnosed with sporadic Inclusion Body Myositis (sIBM) who have been followed at the McMaster Neuromuscular Clinic since 1996. We reviewed patient medical histories in order to compare our findings with similar cohorts, and analyzed quantitative strength data to determine functionality in guiding decisions related to gait assistive devices. Patient information was acquired through retrospective clinic chart review. Our study found knee extension strength decreased significantly as patients transitioned to using more supportive gait assistive devices (P decline to below 30 Nm was particularly indicative of the need for a preliminary device (i.e. cane)(P preventing future falls and improving long-term patient outcomes.

  4. Physical function and muscle strength in sporadic inclusion body myositis.

    Science.gov (United States)

    Jørgensen, Anders N; Aagaard, Per; Nielsen, Jakob L; Christiansen, Mette; Hvid, Lars G; Frandsen, Ulrik; Diederichsen, Louise P

    2017-12-01

    In this study, self-reported physical function, functional capacity, and isolated muscle function were investigated in sporadic inclusion body myositis (sIBM) patients. The 36-item Short Form (SF-36) Health Survey and 2-min walk test (2MWT), timed up & go test (TUG), and 30-s chair stand performance were evaluated. In addition, patients were tested for knee extensor muscle strength (isokinetic dynamometer) and leg extension power (Nottingham power rig). TUG performance was the strongest predictor of self-reported physical function (r2 = 0.56, P function in sIBM patients. Notably, between-limb asymmetry in lower limb muscle strength had a substantial negative impact on motor tasks involving gait function. Muscle Nerve 56: E50-E58, 2017. © 2017 Wiley Periodicals, Inc.

  5. Group G streptococcal myositis in a patient with myeloproliferative neoplasm

    Directory of Open Access Journals (Sweden)

    Monica Midha, MD MBS

    2016-01-01

    Full Text Available While many cases of streptococcal infection are due to Lancefield groups A and B, there has been a rise in reported cases of infections due to group G streptococcus. We present a case of an individual with a hematologic malignancy who developed myositis secondary to group G streptococcus, with no clearly identifiable source of infection. The patient was managed with antibiotic therapy rather than surgical intervention due to high surgical risk related to severe thrombocytopenia. Targeted antibiotics initiated early in the course of disease may prevent the need for surgical intervention. Early diagnosis and treatment are critical to avoid the high morbidity and mortality of life-threatening infections caused by group G streptococcus.

  6. Inclusion Body Myositis: What Most Impacts Patients' Lives.

    Science.gov (United States)

    Gibson, Cynthia; Johnson, Nicholas E; Eastwood, Eileen; Heatwole, Chad

    2016-12-01

    Inclusion body myositis (IBM) is the most common form of idiopathic inflammatory myopathy in adults older than 50 years. Few studies have focused on the functional, physical, and social limitations of this disease. This study identifies pertinent symptoms that impact the health and daily function of patients with IBM. We used semistructured interviews with 10 biopsy-confirmed adults with IBM to identify the psychological, physical, and functional limitations that have the greatest impact on the lives of patients with IBM. Participants with IBM provided 644 direct quotes identifying issues that have the greatest effect on their lives. Two hundred nine individual symptoms and 17 symptomatic themes were identified by patients as having a significant impact on their lives. The symptomatic themes mentioned most frequently involved mobility and ambulation, emotional distress, and activity impairment. Identifying critical issues to patients with IBM is potentially useful for clinicians whose aim is to provide optimal care to patients with IBM.

  7. Different Sarcocystis spp. are present in bovine eosinophilic myositis.

    Science.gov (United States)

    Vangeel, Lieve; Houf, Kurt; Geldhof, Peter; De Preter, Katleen; Vercruysse, Jozef; Ducatelle, Richard; Chiers, Koen

    2013-11-08

    It has been suggested that Sarcocystis species are associated with bovine eosinophilic myositis (BEM). To date, parasite identification in this myopathy has been based on morphological techniques. The aim of the present study was to use molecular techniques to identify Sarcocystis species inside lesions of BEM. Histologically, BEM lesions of 97 condemned carcasses were examined for the presence of Sarcocystis species. Intralesional and extralesional cysts were collected using laser capture microdissection and the species was determined with a PCR-based technique based on 18S rDNA. Intralesional sarcocysts or remnants were found in BEM lesions in 28% of the carcasses. The majority (82%) of intralesional Sarcocystis species were found to be S. hominis. However S. cruzi and S. hirsuta were also found, as well as an unidentified species. It can be concluded that Sarcocystis species present in lesions of BEM are not restricted to one species. Copyright © 2013 Elsevier B.V. All rights reserved.

  8. Risk-Based Classification System of Patients With Newly Diagnosed Acute Lymphoblastic Leukemia

    Science.gov (United States)

    2017-02-13

    Adult B Acute Lymphoblastic Leukemia; Adult T Acute Lymphoblastic Leukemia; Childhood B Acute Lymphoblastic Leukemia; Childhood T Acute Lymphoblastic Leukemia; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Childhood Acute Lymphoblastic Leukemia

  9. Vitamin and mineral supplements in pregnancy and the risk of childhood acute lymphoblastic leukaemia: a case-control study

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    Skegg David CG

    2007-07-01

    Full Text Available Abstract Background An earlier case-control study from Western Australia reported a protective effect of maternal folic acid supplementation during pregnancy on the risk of childhood acute lymphoblastic leukaemia (ALL. The present study tested that association. Methods A national case-control study was conducted in New Zealand. The mothers of 97 children with ALL and of 303 controls were asked about vitamin and mineral supplements taken during pregnancy. Results There was no association between reported folate intake during pregnancy and childhood ALL (adjusted odds ratio (OR 1.1, 95% confidence interval (CI 0.5–2.7. Combining our results with the study from Western Australia and another study from Québec in a meta-analysis gave a summary OR of 0.9 (95% CI 0.8–1.1. Conclusion Our own study, of similar size to the Australian study, does not support the hypothesis of a protective effect of folate on childhood ALL. Neither do the findings of the meta-analysis.

  10. A case-only study of interactions between metabolic enzyme polymorphisms and industrial pollution in childhood acute leukemia.

    Science.gov (United States)

    Yang, You; Tian, Ying; Jin, Xingming; Yan, Chonghuai; Jiang, Fan; Zhang, Yiwen; Tang, Jingyan; Shen, Xiaoming

    2009-09-01

    Cancer risk is modulated by gene-environment interactions between toxic exposure and genetic variation in carcinogen metabolism. Our objective was to assess interactions between exposure to industrial pollutants and polymorphisms affecting cytochrome P450s (CYP1A1 and CYP2E1) and glutathione S-transferases (GSTP1 and GSTT) in childhood acute leukemia (AL). A case-only design was conducted in 123 Chinese children with sporadic AL. Industrial plants in the vicinity were recorded and, if present, their size and proximity to the usual place of residence of AL children was evaluated. Unconditional logistic regression analysis was performed across the AL study group adjusting for age, gender, parental education, occupation and smoking, indoor and outdoor pesticide use, presence of television sets, refrigerators, microwave ovens and furniture material in children's rooms, and electric transformers, power lines, and telecommunication transmitters within 500 m. This analysis revealed an interaction between the GSTT null allele and industrial plants within 500 m of the residences of childhood AL patients (interaction odds ratio, COR=2.96, 95% CI: 1.09-8.01). Furthermore, the COR for the interaction between GSTT null and industrial plants within 50 m was 5.99 (95% CI: 1.41-25.45). Our results suggest an association between proximity to industrial plants and the GSTT null allele in patients with childhood AL.

  11. Disruption of Learning Processes by Chemotherapeutic Agents in Childhood Survivors of Acute Lymphoblastic Leukemia and Preclinical Models

    Directory of Open Access Journals (Sweden)

    Emily B. Bisen-Hersh, Philip N. Hineline, Ellen A. Walker

    2011-01-01

    Full Text Available Objective: With the survival rate of acute lymphoblastic leukemia (ALL surpassing 90 percent within this decade, new research is emerging in the field of late effects. A review of the research investigating the relationship of treatment regimens for ALL to specific late effect deficits, underlying mechanisms, and possible remediation is warranted to support continued studies.Methods: The clinical literature was briefly surveyed to describe the occurrence and topography of late effects, specifically neurocognitive deficits. Additionally, the preclinical literature was reviewed to uncover potential underlying mechanisms of these deficits. The advantages of using rodent models to answer these questions are outlined, as is an assessment of the limited number of rodent models of childhood cancer treatment.Results: The literature supports that childhood survivors of ALL exhibit academic difficulties and are more likely to be placed in a special education program. Behavioral evidence has highlighted impairments in the areas of attention, working memory, and processing speed, leading to a decrease in full scale IQ. Neurophysiological and preclinical evidence for these deficits has implicated white matter abnormalities and acquired brain damage resulting from specific chemotherapeutic agents commonly used during treatment.Conclusions: The exact role of chemotherapeutic agents in learning deficits remains mostly unknown. Recommendations for an improved rodent model of learning deficits in childhood cancer survivors are proposed, along with suggestions for future directions in this area of research, in hopes that forthcoming treatment regimens will reduce or eliminate these types of impairments.

  12. Upregulation of microRNA-21 is a poor prognostic marker in patients with childhood B cell acute lymphoblastic leukemia.

    Science.gov (United States)

    Labib, Hany Abedelmalik; Elantouny, Neveen G; Ibrahim, Nevin F; Alnagar, Ahmed A

    2017-08-01

    Many studies have demonstrated that microRNA-21 (miR-21) is an oncogene and is upregulated in tumor tissue. However, its association with B-cell acute lymphoblastic leukemia (B-ALL) remains poorly understood. The expression of miR-21 was detected by real-time quantitative PCR in 75 children with de novo B-ALL as well as in 50 healthy controls. This study was conducted to evaluate the miR-21 as a biomarker for risk assessment, diagnosis and prognosis. Compared with normal controls, miR-21 expression was significantly upregulated in childhood B-ALL patients. Using the receiver operating characteristic curve 3.23 was selected as the cut-off value of miR-21 expression in distinguishing patients from controls. Patients group with High miR-21 expression was significantly associated with those aged 10 years, lower platelets count, more incidence of CNS infiltration and poorer treatment outcome also, they showed a significantly poorer disease-free survival (DFS) and overall survival (OS) compared to those with low miR-21 expression group. Its expression was an independent prognostic marker according to multivariate analysis. This is the first report demonstrating the upregulation of miR-21 in childhood B-ALL, and its association with poor response to induction therapy, shorter DFS and OS. These results suggest that miR-21 upregulation represent an unfavorable prognostic marker in Childhood B-ALL.

  13. EgoNet identifies differential ego-modules and pathways related to prednisolone resistance in childhood acute lymphoblastic leukemia.

    Science.gov (United States)

    Jiang, Jian; Yin, Xiang-Yun; Song, Xue-Wen; Xie, Dong; Xu, Hui-Juan; Yang, Jing; Sun, Li-Rong

    2017-10-11

    To extract feature ego-modules and pathways in childhood acute lymphoblastic leukemia (ALL) resistant to prednisolone treatment, and further to explore the mechanisms behind prednisolone resistance. EgoNet algorithm was used to identify candidate ego-network modules, mainly via constructing differential co-expression network (DCN); selecting ego genes; collecting ego-network modules; refining candidate modules. Afterwards, statistical significance was calculated for these candidate modules. Biological functions of differential ego-network modules were identified using Reactome database. To verify this proposed method can lead to truly positive findings in clinical settings, support vector machine (SVM) was utilized to compute the AUC values for each significant pathway using 3-fold cross-validation method. To predict the reliability of our findings, another established method (attract) was used to identify the differential attractor modules using the same microarray profile. After eliminating the modules with classification accuracy calculation, module 30 was significant. Module 30 was enriched in APC/C-mediated degradation of cell cycle proteins. The AUC for the significant pathway of APC/C-mediated degradation of cell cycle proteins was 0.915. Although the attract method obtained more modules, the module identified by our proposed method owned more gene nodes, and had more classification ability (AUC = 0.915). One differential ego-network module identified in childhood ALL resistance to prednisolone based on DCN and EgoNet, might be helpful to reveal the mechanisms underlying prednisolone resistance in childhood ALL.

  14. Low-dose daunorubicin in induction treatment of childhood acute lymphoblastic leukemia : No long-term cardiac damage in a randomized study of the Dutch Childhood Leukemia Study Group

    NARCIS (Netherlands)

    Rammeloo, LAJ; Postma, A; Sobotka-Plojhar, MA; Bink-Boelkens, MTE; van der Does-van der Berg, A; Veerman, AJP; Kamps, WA

    Background. To investigate late cardiotoxicity in childhood acute lymphoblastic leukemia (ALL) survivors after induction treatment with or without daunorubicin (DNR; 25 mg/m(2), i.v., weekly, x4, cumulative dose 100 mg/m(2)). Procedure, Cardiac function was assessed in 90 event-free survivors of

  15. Confirmation of childhood acute lymphoblastic leukemia variants, ARID5B and IKZF1, and interaction with parental environmental exposures.

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    Tiffany-Jane Evans

    Full Text Available Genome wide association studies (GWAS have established association of ARID5B and IKZF1 variants with childhood acute lymphoblastic leukemia (ALL. Epidemiological studies suggest that environmental factors alone appear to make a relatively minor contribution to disease risk. The polygenic nature of childhood ALL predisposition together with the timing of environmental triggers may hold vital clues for disease etiology. This study presents results from an Australian GWAS of childhood ALL cases (n = 358 and population controls (n = 1192. Furthermore, we utilised family trio (n = 204 genotypes to extend our investigation to gene-environment interaction of significant loci with parental exposures before conception, and child's sex and age. Thirteen SNPs achieved genome wide significance in the population based case/control analysis; ten annotated to ARID5B and three to IKZF1. The most significant SNPs in these regions were ARID5B rs4245595 (OR 1.63, CI 1.38-1.93, P = 2.13×10(-9, and IKZF1 rs1110701 (OR 1.69, CI 1.42-2.02, p = 7.26×10(-9. There was evidence of gene-environment interaction for risk genotype at IKZF1, whereby an apparently stronger genetic effect was observed if the mother took folic acid or if the father did not smoke prior to pregnancy (respective interaction P-values: 0.04, 0.05. There were no interactions of risk genotypes with age or sex (P-values >0.2. Our results evidence that interaction of genetic variants and environmental exposures may further alter risk of childhood ALL however, investigation in a larger population is required. If interaction of folic acid supplementation and IKZF1 variants holds, it may be useful to quantify folate levels prior to initiating use of folic acid supplements.

  16. [Cytopathologic features of childhood acute leukemia at the Hospital de Especialidades Pediátricas, Chiapas, Mexico].

    Science.gov (United States)

    Lepe-Zúñiga, José Luis; Jerónimo-López, Francisco Javier; Hernández-Orantes, Jorge Gregorio

    Childhood acute leukemia cytological features are unknown in Chiapas, Mexico. Defining these features is important because this is a relatively isolated population with high consanguinity index, and these aspects could determine differences in responses to treatment and outcome. Eighty-one childhood acute leukemia cases treated at the Hospital de Especialidades Pediátricas in Chiapas were characterized by morphology, immunophenotype, genotype, initial risk assignment and status at the time of the study. The proportion of leukemic cell types found in this study was B cell, 75.3%; myeloid, 16%; T cell, 3.7% and NK 1.2%. In B cell leukemia, genetic alterations were present in 40.6% of cases and had a specific outcome regardless of initial risk assessment. Cases with MLL gene alteration died within a month from diagnosis. Translocations were present in 17.5% B cases; t(1;19) was present in those with a favorable outcome. The t(12;21) translocation was related to initial remission and midterm relapse and dead. Hyperdiploidy was present in 20% of B cell cases with good outcome. In 38.5%of myeloid cases were translocations and karyotypic abnormalities. Short-term outcome in this group has been poor; 69% have died or abandoned treatment in relapse from 15 days to 37 months after diagnosis. Relative frequency of different types of acute leukemia in patients treated at a tertiary level pediatric hospital in Chiapas, Mexico, was similar to the one found in other parts of the country. Patients' outcome, under a standardized treatment, differs according to the group, the subgroup and the presence and type of genetic alterations. Copyright © 2017 Hospital Infantil de México Federico Gómez. Publicado por Masson Doyma México S.A. All rights reserved.

  17. Cognitive, behaviour, and academic functioning in adolescent and young adult survivors of childhood acute lymphoblastic leukaemia: a report from the Childhood Cancer Survivor Study.

    Science.gov (United States)

    Jacola, Lisa M; Edelstein, Kim; Liu, Wei; Pui, Ching-Hon; Hayashi, Robert; Kadan-Lottick, Nina S; Srivastava, Deokumar; Henderson, Tara; Leisenring, Wendy; Robison, Leslie L; Armstrong, Gregory T; Krull, Kevin R

    2016-10-01

    Survivors of childhood acute lymphoblastic leukaemia (ALL) are at risk for neurocognitive deficits that affect development in adolescence and young adulthood, and influence educational attainment and future independence. We examined a large and diverse cohort of survivors to identify risk predictors and modifiers of these outcomes. In this cohort study, cognitive and behaviour symptoms were assessed via a standardised parent questionnaire for 1560 adolescent survivors of ALL diagnosed between 1970 and 1999. Clinically significant symptoms (≥90th percentile) and learning problems were compared between survivors and a sibling cohort. Multivariable regression models were used to examine associations with demographic and treatment characteristics. Models were adjusted for inverse probability of sampling weights to reflect undersampling of ALL survivors in the expansion cohort. In a subset of survivors with longitudinal data (n=925), we examined associations between adolescent symptoms or problems and adult educational attainment. Compared with siblings, survivors treated with chemotherapy only were more likely to demonstrate headstrong behaviour (155 [19%] of 752 survivors vs 88 [14%] of 610 siblings, p=0·010), inattention-hyperactivity (15 [19%] vs 86 [14%], p4·3 g/m2) conferred increased risk of inattention-hyperactivity (relative risk [RR] 1·53, 95% CI 1·13-2·08). Adolescent survivors with cognitive or behaviour problems and those with learning problems were less likely to graduate from college as young adults than adolescent survivors without cognitive or behaviour problems. Although modern therapy for childhood ALL has eliminated the use of cranial radiation therapy, adolescent survivors treated with chemotherapy only remain at increased risk for cognitive, behaviour, and academic problems that adversely affect adult education outcomes. National Cancer Institute, American Lebanese-Syrian Associated Charities. Copyright © 2016 Elsevier Ltd. All rights

  18. Evaluation of mRNA Expression Profile of ABCG2/BCRP in Childhood Acute Lymphoblastic Leukemia

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    M Entezar-e-Ghaem

    2013-12-01

    Conclusion: Results of this study showed no effect of ABCG2/BCRP expression level on MDR development in ALL. Accordingly, clinical value of ABCG2/BCRP expression profile determination was rejected as the prognosis value for childhood ALL in our geographical area.

  19. Beneficial role of rapamycin in experimental autoimmune myositis.

    Directory of Open Access Journals (Sweden)

    Nicolas Prevel

    Full Text Available We developed an experimental autoimmune myositis (EAM mouse model of polymyositis where we outlined the role of regulatory T (Treg cells. Rapamycin, this immunosuppressant drug used to prevent rejection in organ transplantation, is known to spare Treg. Our aim was to test the efficacy of rapamycin in vivo in this EAM model and to investigate the effects of the drug on different immune cell sub-populations.EAM is induced by 3 injections of myosin emulsified in CFA. Mice received rapamycin during 25 days starting one day before myosin immunization (preventive treatment, or during 10 days following the last myosin immunization (curative treatment.Under preventive or curative treatment, an increase of muscle strength was observed with a parallel decrease of muscle inflammation, both being well correlated (R(2 = -0.645, p<0.0001. Rapamycin induced a general decrease in muscle of CD4 and CD8 T cells in lymphoid tissues, but spared B cells. Among T cells, the frequency of Treg was increased in rapamycin treated mice in draining lymph nodes (16.9 ± 2.2% vs. 9.3 ± 1.4%, p<0.001, which were mostly activated regulatory T cells (CD62L(lowCD44(high: 58.1 ± 5.78% vs. 33.1 ± 7%, treated vs. untreated, p<0.001. In rapamycin treated mice, inhibition of proliferation (Ki-67(+ is more important in effector T cells compared to Tregs cells (p<0.05. Furthermore, during preventive treatment, rapamycin increased the levels of KLF2 transcript in CD44(low CD62L(high naive T cell and in CD62L(low CD44(high activated T cell.Rapamycin showed efficacy both as curative and preventive treatment in our murine model of experimental myositis, in which it induced an increase of muscle strength with a parallel decrease in muscle inflammation. Rapamycin administration was also associated with a decrease in the frequency of effector T cells, an increase in Tregs, and, when administered as preventive treatment, an upregulation of KFL2 in naive and activated T cells.

  20. An Autoimmune Myositis-Overlap Syndrome Associated With Autoantibodies to Nuclear Pore Complexes

    Science.gov (United States)

    Senécal, Jean-Luc; Isabelle, Catherine; Fritzler, Marvin J.; Targoff, Ira N.; Goldstein, Rose; Gagné, Michel; Raynauld, Jean-Pierre; Joyal, France; Troyanov, Yves; Dabauvalle, Marie-Christine

    2014-01-01

    Abstract Autoimmune myositis encompasses various myositis-overlap syndromes, each being identified by the presence of serum marker autoantibodies. We describe a novel myositis-overlap syndrome in 4 patients characterized by the presence of a unique immunologic marker, autoantibodies to nuclear pore complexes. The clinical phenotype was characterized by prominent myositis in association with erosive, anti-CCP, and rheumatoid factor-positive arthritis, trigeminal neuralgia, mild interstitial lung disease, Raynaud phenomenon, and weight loss. The myositis was typically chronic, relapsing, and refractory to corticosteroids alone, but remitted with the addition of a second immunomodulating drug. There was no clinical or laboratory evidence for liver disease. The prognosis was good with 100% long-term survival (mean follow-up 19.5 yr). By indirect immunofluorescence on HEp-2 cells, sera from all 4 patients displayed a high titer of antinuclear autoantibodies (ANA) with a distinct punctate peripheral (rim) fluorescent pattern of the nuclear envelope characteristic of nuclear pore complexes. Reactivity with nuclear pore complexes was confirmed by immunoelectron microscopy. In a cohort of 100 French Canadian patients with autoimmune myositis, the nuclear pore complex fluorescent ANA pattern was restricted to these 4 patients (4%). It was not observed in sera from 393 adult patients with systemic sclerosis (n = 112), mixed connective tissue disease (n = 35), systemic lupus (n = 94), rheumatoid arthritis (n = 45), or other rheumatic diseases (n = 107), nor was it observed in 62 normal adults. Autoantibodies to nuclear pore complexes were predominantly of IgG isotype. No other IgG autoantibody markers for defined connective tissue diseases or overlap syndromes were present, indicating a selective and highly focused immune response. In 3 patients, anti-nuclear pore complex autoantibody titers varied in parallel with myositis activity, suggesting a pathogenic

  1. Gestational age, mode of birth and breastmilk feeding all influence acute early childhood gastroenteritis: a record-linkage cohort study.

    Science.gov (United States)

    Bentley, Jason P; Simpson, Judy M; Bowen, Jenny R; Morris, Jonathan M; Roberts, Christine L; Nassar, Natasha

    2016-04-27

    Acute gastroenteritis (AGE) is a leading cause of infectious morbidity in childhood. Clinical studies have implicated caesarean section, early birth and formula feeding in modifying normal gut microbiota development and immune system homeostasis in early life. Rates of early birth and cesarean delivery are also increasing worldwide. This study aimed to investigate the independent and combined associations of the mode and timing of birth and breastmilk feeding with AGE hospitalisations in early childhood. Population-based record-linkage study of 893,360 singleton livebirths of at least 33 weeks gestation without major congenital conditions born in hospital, New South Wales, Australia, 2001-2011. Using age at first AGE hospital admission, Cox-regression was used to estimate the associations for gestational age, vaginal birth or caesarean delivery by labour onset and formula-only feeding while adjusting for confounders. There were 41,274 (4.6 %) children admitted to hospital at least once for AGE and the median age at first admission was 1.4 years. Risk of AGE admission increased with decreasing gestational age (37-38 weeks: 15 % increased risk, 33-36 weeks: 25 %), caesarean section (20 %), planned birth (17 %) and formula-only feeding (18 %). The rate of AGE admission was highest for children who were born preterm by modes of birth other than vaginal birth following the spontaneous onset of labour and who received formula-only at discharge from birth care (62-78 %). Vaginal birth following spontaneous onset of labour at 39+ weeks gestation with any breastfeeding minimised the risk of gastroenteritis hospitalisation in early childhood. Given increasing trends in early planned birth and caesarean section worldwide, these results provide important information about the impact obstetric interventions may have on the development of the infant gut microbiota and immunity.

  2. Paternal intake of folate and vitamins B6 and B12 before conception and risk of childhood acute lymphoblastic leukemia.

    Science.gov (United States)

    Bailey, Helen D; Miller, Margaret; Greenop, Kathryn R; Bower, Carol; Attia, John; Marshall, Glenn M; Armstrong, Bruce K; Milne, Elizabeth

    2014-12-01

    We investigated whether paternal dietary intake of folate before conception is associated with the risk of childhood acute lymphoblastic leukemia (ALL) in a nationwide case-control study. Data on dietary folate intake during the 6 months before the child's conception were collected from 285 case fathers and 595 control fathers using a dietary questionnaire. Nutrient intake was quantified using a customized computer software package based on Australian food composition databases. Data on folate intake were analyzed using unconditional logistic regression, adjusting for study-matching variables, total energy, and potentially confounding variables. In a subset of 229 cases and 420 controls, data on vitamin B6 and vitamin B12 intake were also analyzed. No consistent associations were seen with paternal dietary intake of folate or vitamin B6. Higher levels of paternal dietary vitamin B12 were appeared to be associated with an increased risk of childhood ALL, with those in the highest tertile of consumption having an OR of 1.51 (0.97, 2.36). The use of supplements containing folate and vitamins B6 or B12 was rare. We did not find any biologically plausible evidence that paternal nutrition in the period leading up to conception was associated with childhood ALL. Our finding for vitamin B12 may be a chance finding, given the number of analyses performed, or be attributable to participation bias because parents with a tertiary education had the lowest level of B12 intake and tertiary education was more common among control than case parents.

  3. Effects of Maternal Diet During Pregnancy on the Risk of Childhood Acute Lymphoblastic Leukemia: A Systematic Review.

    Science.gov (United States)

    Abiri, Behnaz; Kelishadi, Roya; Sadeghi, Homa; Azizi-Soleiman, Fatemeh

    2016-10-01

    Acute lymphoblastic leukemia (ALL) is the most common type of leukemia in children that can be affected by maternal diet. The aim of this study was to evaluate maternal dietary risk factors of ALL. We searched MEDLINE, Cochrane Library, Springer Link, Wiley Online, Science Direct, Mosby, ISI Web of Science, OVID, ProQuest, and Scopus from database inception until February 2, 2016. Two reviewers scanned titles, abstracts, and keywords of articles after excluding duplicates. We included case-control studies evaluating the relationship between maternal diet during pregnancy and childhood ALL. The search resulted in 2,940 papers, of which 11 full-text articles met the criteria for inclusion in the review and were analyzed. The finding of these studies suggest that maternal diet composed largely of vegetables, fruits, and protein sources before and during pregnancy can reduce the risk of ALL in offspring. Maternal alcohol intake had no effect. Nevertheless, inherent limitations of case-control studies like measurement error, random error, recall bias, and selection bias preclude conclusive evidence. Persuading pregnant women to follow a healthy diet rich in fruits, vegetables, and protein may reduce the risk of childhood ALL. Avoiding alcohol intake seems prudent.

  4. High resolution melting curve analysis, a rapid and affordable method for mutation analysis in childhood acute myeloid leukemia

    Directory of Open Access Journals (Sweden)

    Yin eLiu

    2014-09-01

    Full Text Available Background: Molecular genetic alterations with prognostic significance have been described in childhood acute myeloid leukemia (AML. The aim of this study was to establish cost-effective techniques to detect mutations of FMS-like tyrosine kinase 3 (FLT3, Nucleophosmin 1 (NPM1, and a partial tandem duplication within the mixed lineage leukemia (MLL-PTD genes in childhood AML. Procedure: Ninety-nine children with newly diagnosed AML were included in this study. We developed a fluoresent dye SYTO-82 based high resolution melting curve (HRM anaylsis to detect FLT3 internal tandem duplication (FLT3-ITD, FLT3 tyrosine kinase domain (FLT3-TKD and NPM1 mutations. MLL-PTD was screened by real-time quantitative PCR. Results: The HRM methodology correlated well with gold standard Sanger sequencing with less cost. Among the 99 patients studied, the FLT3-ITD mutation was associated with significantly worse event free survival (EFS. Patients with the NPM1 mutation had significantly better EFS and overall survival. However, HRM was not sensitive enough for minimal residual disease monitoring. Conclusions: HRM was a rapid and efficient method for screening of FLT3 and NPM1 gene mutations. It was both affordable and accurate, especially in resource underprivileged regions. Our results indicated that HRM could be a useful clinical tool for rapid and cost effective screening of the FLT3 and NPM1 mutations in AML patients.

  5. The MTHFR C677T and A1298C polymorphisms and susceptibility to childhood acute lymphoblastic leukemia in Portugal.

    Science.gov (United States)

    Oliveira, Elisabete; Alves, Sandra; Quental, Sofia; Ferreira, Fátima; Norton, Lucília; Costa, Vitor; Amorim, António; Prata, Maria João

    2005-08-01

    Methylenetetrahydrofolate reductase (MTHFR) is an essential enzyme in folate metabolism and in DNA methylation and synthesis. The role of two common polymorphisms at the MTHFR gene, C677T and A1298C, in the etiology of childhood or adult acute lymphoblastic leukemia (ALL) has been previously investigated. Although a protective effect of MTHFR*677T against ALL was systematically reported, the magnitude of the effect appeared to be influenced by population-specific gene-environmental interactions. The evidence of the role of MTHFR*1298C in ALL susceptibility was less consistent, emphasizing the need for enlarging molecular epidemiologic studies to independent trials from different populations. The authors analyzed in North Portugal the association between variations at the two MTHFR positions and risk of ALL by comparing genotypes and gene frequencies in 103 affected children with those in 111 healthy controls. None of the variations was found to significantly affect the risk of developing childhood ALL in North Portugal, and this finding per se is of relevance in further studies aimed at assessing the etiology of the pathology in this specific population. Despite the absence of statistical significance, these data revealed that the frequency of MTHFR*677T was lower in patients than in controls, a result that is congruent with other reports and with the functional model usually invoked to explain its ALL protective effect. Concerning MTHFR1298*C, this study failed to corroborate previous findings of decreased risk of ALL in the presence of the variant.

  6. Breastfeeding and nutrition to 2 years of age and risk of childhood acute lymphoblastic leukemia and brain tumors.

    Science.gov (United States)

    Greenop, Kathryn R; Bailey, Helen D; Miller, Margaret; Scott, Rodney J; Attia, John; Ashton, Lesley J; Downie, Peter; Armstrong, Bruce K; Milne, Elizabeth

    2015-01-01

    Acute lymphoblastic leukemia (ALL) and childhood brain tumors (CBT) are 2 of the most common forms of childhood cancer, but little is known of their etiology. In 2 nationwide case-control studies we investigated whether breastfeeding, age of food introduction, or early diet are associated with the risk of these cancers. Cases aged 0-14 years were identified from Australian pediatric oncology units between 2003 and 2007 (ALL) and 2005 and 2010 (CBT) and population-based controls through nationwide random-digit dialing. Mothers completed questionnaires giving details of infant feeding up to the age of 2 yr. Data from 322 ALL cases, 679 ALL controls, 299 CBT cases, and 733 CBT controls were analysed using unconditional logistic regression. Breastfeeding was associated with a reduced risk of ALL [odds ratio (OR) = 0.52, 95% confidence interval (CI): 0.32, 0.84), regardless of duration. Introduction of artificial formula within 14 days of birth was positively associated with ALL (OR = 1.57, 95% CI: 1.03, 2.37), as was exclusive formula feeding to 6 mo (OR = 1.81, 95% CI: 1.07, 3.05). No associations were seen between breastfeeding or formula use and risk of CBT. Our results suggest that breastfeeding and delayed introduction of artificial formula may reduce the risk of ALL but not CBT.

  7. The impact of CYP3A5*3 on risk and prognosis in childhood acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Borst, Louise; Wallerek, Sandra; Dalhoff, Kim Peder

    2011-01-01

    of experiencing an event was almost eight times higher compared to those having at least one A allele (P = 0.045, hazard ratio = 7.749; 95% CI, 1.044-57.52). Conclusions:  This study shows that genetics may play a role in the risk of developing childhood ALL and indicates that improved treatment stratification......Objectives:  Acute lymphoblastic leukemia (ALL) is the most common cancer in childhood; however, little is known of the molecular etiology and environmental exposures causing the disease. Cytochrome P450 3A5 (CYP3A5) plays a crucial role in the catalytic oxidation of endogenous metabolites...... and toxic substances, including chemotherapeutic agents. The aim of this study was to investigate the role of a single-nucleotide polymorphism (CYP3A5*3 6986A>G), which renders low enzyme activity, in the risk of developing ALL and in the outcome for children with ALL. Patients and methods:  Six hundred...

  8. Outcome of modified St Jude total therapy 13A for childhood acute lymphoblastic leukemia in the southeast region of Turkey.

    Science.gov (United States)

    Koc, Ahmet; Aycicek, Ali; Ozdemir, Zeynep C; Soker, Murat; Varma, Mustafa

    2013-01-01

    To fill the gap in the current data on childhood acute lymphoblastic leukemia (ALL) in low-income and middle-income countries. This study included 106 children between the ages of 1 and 17 years with newly diagnosed ALL monitored between 1999 and 2010. All the patients were treated with the modified St Jude Total 13A treatment plan at the Pediatric Hematology Clinic at Harran University. Sixty-eight (64.2%) patients were boys and 38 (35.8%) were girls. The median age at diagnosis was 5.9 ± 3.7 years. Thirty-eight (35.8%) children were classified as standard risk, 53 (39.3%) were intermediate risk, and 15 (14.2%) were high risk. Thirteen (12.3%) children died in induction before the remission date (43 d of remission induction). Of all the 93 (100%) patients who completed remission induction therapy and whose bone marrow were in remission, 5 (4.7%) had a bone marrow relapse, 1 (0.9%) had a retinal relapse, and 5 (4.7%) had secondary acute myeloid leukemia. At a median follow-up of 44 months (range, 0.36 to 135.5 mo), the estimated 5-year overall survival and event-free survival were 77.4 ± 5% and 68.9 ± 6.5%, respectively. The estimated 5-year overall survival for boys and girls was 76.5 ± 6% and 65.8 ± 8%, respectively (P = 0.182). St Jude Total 13A treatment protocols to treat childhood ALL can be successfully adapted, which suggests that such an approach may be useful in low socioeconomic regions; however, it should be noted that secondary leukemia can occur at a high rate.

  9. Glycogen Synthase Kinase-3β (GSK-3β) and Nuclear Factor Kappa-B (NFKB) in Childhood Acute Lymphoblastic Leukemia.

    Science.gov (United States)

    Tovar, Cristian Fabian Layton; Zerón, Hugo Mendieta; Romero, Maria Del Socorro Camarillo; Sánchez, Yanko V Fabila; Romero, Isidoro Tejocote

    2016-01-01

    Acute lymphocytic leukemia (ALL) is the most common hematologic malignancy in early childhood. In children with acute lymphoblastic leukemia (ALL), the activity of glycogen synthase kinase (GSK-3β) has been associated with changes in the transcriptional activity and expression of nuclear factor kappa beta (NFKB) in the mononuclear cells of bone marrow. The aim of the study was to determine the possible role of glycogen synthase kinase 3beta (GSK-3β) and nuclear factor kappa beta (NFKB) as prognostic variables in pediatric patients with ALL. This was a descriptive, transversal, and observational study. Bone marrow and blood samples were obtained from 30 children with newly-diagnosed ALL, who were seen at the Hematology-Oncology Service, Hospital para el Niño (HPN), Toluca, Mexico, from 2014‒2015. Anthropometric variables, clinical lab results, immunophenotype and cytogenetic abnormalities were registered. GSK-3β was evaluated through immunohistochemistry, and NFKB messenger RNA (mRNA) with real-time polymerase chain reaction (qPCR). The cases of ALL were classified into two groups of risk: high and habitual. Thirty patients were included in this study, with a mean age of 7.1 years (range 2‒13 years). Twenty-one were male and 9 female. Employing the morphological classification, 26 patients had type L1 ALL and the remaining 4 patients had type L2 ALL. Abnormal genes were found in 7 (23.33%) patients, ETV-RUNX1 in 3, followed by TCF3-PBX1 (two), STL1-TAL1 (one), and BCR-ABL1 (one). NFKB relative expression levels, in comparison to the GSK-3β immunohistochemistry results of the bone marrow samples, showed significant differences between positive and negative cases (p = 0.001) and between weak-positive and negative cases (p = 0.002). These results suggest that GSK-3β may be a prognostic biomarker in childhood ALL.

  10. Acute unilateral isolated ptosis.

    Science.gov (United States)

    Court, Jennifer Helen; Janicek, David

    2015-01-05

    A 64-year-old man presented with a 2-day history of acute onset painless left ptosis. He had no other symptoms; importantly pupils were equal and reactive and eye movements were full. There was no palpable mass or swelling. He was systemically well with no headache, other focal neurological signs, or symptoms of fatigue. CT imaging showed swelling of the levator palpebrae superioris suggestive of myositis. After showing no improvement over 5 days the patient started oral prednisolone 30 mg reducing over 12 weeks. The ptosis resolved quickly and the patient remains symptom free at 6 months follow-up. Acute ptosis may indicate serious pathology. Differential diagnoses include a posterior communicating artery aneurysm causing a partial or complete third nerve palsy, Horner's syndrome, and myasthenia gravis. A careful history and examination must be taken. Orbital myositis typically involves the extraocular muscles causing pain and diplopia. Isolated levator myositis is rare. 2015 BMJ Publishing Group Ltd.

  11. Individualized 6-mercaptopurine increments in consolidation treatment of childhood acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Tulstrup, Morten; Frandsen, Thomas L; Abrahamsson, Jonas

    2018-01-01

    OBJECTIVES: This randomized controlled trial tested the hypothesis that children with non-high-risk acute lymphoblastic leukemia could benefit from individualized 6-mercaptopurine increments during consolidation therapy (NCT00816049). Primary and secondary end points were end of consolidation...

  12. Methotrexate resistance in relation to treatment outcome in childhood acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Wojtuszkiewicz, Anna; Peters, Godefridus J; van Woerden, Nicole L

    2015-01-01

    BACKGROUND: Methotrexate (MTX) eradicates leukemic cells by disrupting de novo nucleotide biosynthesis and DNA replication, resulting in cell death. Since its introduction in 1947, MTX-containing chemotherapeutic regimens have proven instrumental in achieving curative effects in acute lymphoblast...

  13. Resistance to different classes of drugs is associated with impaired apoptosis in childhood acute lymphoblastic leukemia

    NARCIS (Netherlands)

    A. Holleman (Amy); M.L. den Boer (Monique); K.M. Kazemier (Karin); G.E. Janka-Schaub (Gritta); R. Pieters (Rob)

    2003-01-01

    textabstractResistance of leukemic cells to chemotherapeutic agents is associated with an unfavorable outcome in pediatric acute lymphoblastic leukemia (ALL). To investigate the underlying mechanisms of cellular drug resistance, the activation of various apoptotic parameters in

  14. [Inclusion body myositis--a rarely recognized disorder].

    Science.gov (United States)

    Dézsi, Livia; Danielsson, Olof; Gáti, István; Varga, Edina Tímea; Vécsei, László

    2013-03-30

    Inclusion body myositis is the most common disabling inflammatory myopathy in the elderly. It is more frequent in men and after the age of 50 years. Inflammatory and degenerative features coexist. There is a T-cell mediated autoimmunity driven by in situ clonally expanded cytotoxic CD8-positive T-cells invading non-necrotic muscle fibres expressing MHC-I antigen. The hallmarks of degeneration are the deposition of protein aggregates and the formation of vesicles. The course of the disease is slow and the diagnosis is usually set after several years. The muscle weakness and wasting is assymetric, affecting predominantly distal muscles of the upper extremity and proximal muscles of the legs. The signs and clinical course can be characteristic, but the diagnosis is established by muscle biopsy. There is currently no evidence based effective treatment for sIBM. Prednisone, azathioprine, methotrexate, cyclosporine and IFN-beta failed. Oxandrolon did not improve symptoms. Treatment with intravenous immunglobuline (IVIG) induced in some patients a transient improvement of swallowing and of muscle strenght, but the overall study results were negative. A T-cell depleting monoclonal antibody (alemtuzumab), in a small uncontrolled study slowed down disease progression for a six-month period. Repeated muscle biopsies showed the reduction of T-cells in the muscle and the suppression of some degeneration associated molecules. An effective therapeutic mean should act on both aspects of the pathomechanism, on the inflammatory and the degenerative processes as well.

  15. Family characteristics as risk factors for childhood acute lymphoblastic leukemia: a population-based case-control study.

    Directory of Open Access Journals (Sweden)

    Martin Feller

    Full Text Available BACKGROUND: To date, few risk factors for childhood acute lymphoblastic leukemia (ALL have been confirmed and the scientific literature is full of controversial "evidence." We examined if family characteristics, particularly maternal and paternal age and number of older siblings, were risk factors for childhood acute lymphoblastic leukemia (ALL. METHODOLOGY/PRINCIPAL FINDINGS: In this population-based nationwide matched case-control study, patients 0-14 years of age with ALL diagnosed 1991-2006 and registered in the Swiss Childhood Cancer Registry were linked with their census records of 1990 and 2000. Eight controls per case were selected from the census. The association between family characteristics and ALL was analyzed by conditional logistic regressions. We found that increasing maternal age was associated with incidence of ALL in the offspring (OR per 5-year increase in maternal age 1.18, 95% CI 1.05-1.31; p = 0.004, remaining stable (trend OR 1.14, 95% CI 0.99-1.31; p = 0.060 after adjustment for other risk factors. The association with paternal age was weaker (OR per 5-year increase 1.14, 95% CI 1.01-1.28, p = 0.032 and disappeared after adjustments. Number of older siblings was not associated with risk of ALL in the overall group of children aged 0-14 years at diagnosis. However, we found a negative trend between number of older siblings and ALL diagnosed at age 0-4 years (OR per sibling 0.85, 95% CI 0.68-1.06; p = 0.141 and a positive trend for ALL diagnosed at age 5-9 (OR 1.34, 95% CI 1.05-1.72; p = 0.019, with some evidence for an effect modification (p-value for interaction  = 0.040. CONCLUSIONS: As in other studies, increasing maternal, but not paternal age was associated with risk of ALL. We found only a weak association with the number of older siblings, suggesting a delay in disease manifestation rather than a decrease in incidence.

  16. High-resolution Antibody Array Analysis of Childhood Acute Leukemia Cells*

    Science.gov (United States)

    Kanderova, Veronika; Kuzilkova, Daniela; Stuchly, Jan; Vaskova, Martina; Brdicka, Tomas; Fiser, Karel; Hrusak, Ondrej; Lund-Johansen, Fridtjof

    2016-01-01

    Acute leukemia is a disease pathologically manifested at both genomic and proteomic levels. Molecular genetic technologies are currently widely used in clinical research. In contrast, sensitive and high-throughput proteomic techniques for performing protein analyses in patient samples are still lacking. Here, we used a technology based on size exclusion chromatography followed by immunoprecipitation of target proteins with an antibody bead array (Size Exclusion Chromatography-Microsphere-based Affinity Proteomics, SEC-MAP) to detect hundreds of proteins from a single sample. In addition, we developed semi-automatic bioinformatics tools to adapt this technology for high-content proteomic screening of pediatric acute leukemia patients. To confirm the utility of SEC-MAP in leukemia immunophenotyping, we tested 31 leukemia diagnostic markers in parallel by SEC-MAP and flow cytometry. We identified 28 antibodies suitable for both techniques. Eighteen of them provided excellent quantitative correlation between SEC-MAP and flow cytometry (p leukemia. In this assay, we used 632 different antibodies and detected 501 targets. Of those, 47 targets were differentially expressed between at least two of the three acute leukemia subgroups. The CD markers correlated with immunophenotypic categories as expected. From non-CD markers, we found DBN1, PAX5, or PTK2 overexpressed in B-cell precursor acute lymphoblastic leukemias, LAT, SH2D1A, or STAT5A overexpressed in T-cell acute lymphoblastic leukemias, and HCK, GLUD1, or SYK overexpressed in acute myeloid leukemias. In addition, OPAL1 overexpression corresponded to ETV6-RUNX1 chromosomal translocation. In summary, we demonstrated that SEC-MAP technology is a powerful tool for detecting hundreds of proteins in clinical samples obtained from pediatric acute leukemia patients. It provides information about protein size and reveals differences in protein expression between particular leukemia subgroups. Forty-seven of SEC-MAP identified

  17. A review of chronic and acute physical activity participation on neuroelectric measures of brain health and cognition during childhood.

    Science.gov (United States)

    Hillman, Charles H; Kamijo, Keita; Scudder, Mark

    2011-06-01

    A growing body of research has detailed the beneficial relation of chronic participation in--and acute responses to--physical activity on aspects of cognition that underlie scholastic achievement. Here, we review the relevant neuroelectric findings on this beneficial relation in children, providing support for the influence of physical activity on specific cognitive processes that comprise academic performance. A review of studies examining physical activity and neuroelectric concomitants of cognition during childhood is described. When applicable, research involving adult populations is also described to better inform on this relationship in children. Collectively, the data support a beneficial relation of chronic and acute participation in physical activity to brain health and cognition. The results suggest more effective allocation of cognitive processes involved in stimulus engagement and action monitoring during tasks requiring variable amounts of cognitive control in children. Physical activity may influence brain health and cognition in children, leading to enhanced scholastic performance and greater overall effective functioning across the lifespan. Copyright © 2011 Elsevier Inc. All rights reserved.

  18. Current status of anti-diarrheal and anti-secretory drugs in the management of acute childhood diarrhea.

    Science.gov (United States)

    Alam, Seema; Bhatnagar, Shrish

    2006-08-01

    Each year 1.8 million children die due to diarrheal diseases. Indiscriminate use of antibiotics has resulted in increasing resistance to commonly used antibiotics. Moreover the recent outbreaks of shigella and cholera have revealed multi-drug resistance strains. There is a need for review of recommended antibiotics for shigellosis. From recent data it emerges that fluoroquinolones should be the first line of therapy and cephalosporins to be used as the second line. Among the anti-cholera antibiotics, tetracyclines which were the drug of choice for adults, has the advantage of high sensitivity and low cost. Single dose doxycycline would have minimal side effects, hence can be the drug of choice even in children. We should not allow the business pressures to force usage of probiotics and racecadotril as their role in the management of acute diarrhea is yet to be established. Nitazoxanide has high efficacy against Cryptosporodial diarrhea only. Strict adherence to the recommendations for the management of acute childhood diarrhea is needed or else we dilute the effect of standard management.

  19. Sjögren's syndrome-associated myositis with germinal centre-like structures.

    Science.gov (United States)

    Espitia-Thibault, Alexandra; Masseau, Agathe; Néel, Antoine; Espitia, Olivier; Toquet, Claire; Mussini, Jean-Marie; Hamidou, Mohamed

    2017-02-01

    Muscular impairment is a rare systemic manifestation of SS that is rarely described in the literature and classically non-specific, both clinically and histologically. We reviewed the cases of 4 patients with primary SS presenting with myositis and a common histologic pattern on muscular biopsy with germinal centre-like structures resembling that which occurs in salivary glands. We analysed the data files of patients with SS who had muscular manifestations and underwent a muscular biopsy. Among 23 patients with SS who had muscle biopsies, 13 had non-specific myositis and 10 (4 primary and 6 secondary SS) had a common histologic pattern consisting of germinal centre-like structures. We analysed the data files of the 4 patients with primary SS presenting with myositis with muscular germinal-centre like structures. The 4 patients had an unspecific clinical presentation, with myalgias, muscular weakness and normal or elevated values of CPK. In the four patients, SS-associated myositis had common histologic characteristics, with endomysial and perimysial inflammatory infiltrate. The cellular infiltrate was composed predominantly of CD4+ T lymphocytes and B lymphocytes. The B and T CD4+ cells infiltrates may gather into masses, even forming lymphoid follicles. Three patients were treated with corticosteroids and/or hydroxychloroquine with improvement of myositis and 1 patient was lost to follow-up. We describe four patients with a common histologic appearance of myositis with lymphoid follicles associated with primary SS. The clinical presentation was non-specific and non-severe, with favorable outcome with corticosteroids and/or hydroxycholoroquine. The discovery of this particular histologic appearance in a muscle biopsy independent of the final diagnosis should indicate the possibility of SS. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. [Acute pancreatitis in childhood. Is it the same disease in adults?].

    Science.gov (United States)

    Baeza-Herrera, Carlos; Velasco-Soria, Luis; Mora-Hernández, Francisco; Godoy-Esquivel, Arturo Hermilo; Osorio-Agüero, Cecilia Dinorah

    2003-01-01

    Acute pancreatitis in children is an uncommon, little known, poorly defined disease and thus is rarely considered in diagnosis of pediatric abdominal pain. It is rare but is being recognized more frequently, and differs from the disease in the adult both in etiology and therapeutic approach. Fifty children with acute pancreatitis were managed. Their history and postoperative course were analyzed in a retrospective study. The clinical presentation was unremarkable; all patients had abdominal pain, specially in epigastrium, and vomiting was the only other clinical sign exhibited by > 80%. More than 40 biliary diseases were the cause of pancreatitis; trauma was the cause in 30%. Diagnosis could be difficult and unnecessary laparotomy was performed in 16 cases (32.0%) instances of suspected acute abdomen. Morbidity included sepsis, diabetic cetoacidosis, and pancreatic pseudocyst. Biliary disease is a frequent cause of both pediatric and adult pancreatitis. They are differences in clinical course and prognosis. In children, pancreatitis is usually confused with appendicitis.

  1. Use of intravenous immunoglobulin therapy for myositis: an audit in South Australian patients.

    Science.gov (United States)

    Foreman, Caroline; Russo, Paul; Davies, Noelene; Hissaria, Pravin; Proudman, Susanna; Hughes, Tiffany; Limaye, Vidya

    2017-01-01

    In South Australia, between 2000 and 2014, 57 patients with idiopathic inflammatory myositis (IIM) were treated with intravenous immunoglobulin (IVIg). We reviewed disease characteristics to determine predictors of response to therapy and IVIg dosing and duration to identify opportunities to rationalise IVIg use. Patients with dermatomyositis/polymyositis had a response rate of 77% and were more likely than inclusion body myositis to respond to therapy. Consideration should be given to the use of the lowest possible dose of IVIg and to the undertaking of trials of cessation of IVIg in patients with stable IIM. © 2017 Royal Australasian College of Physicians.

  2. A Rare Case of Sporadic Inclusion Body Myositis (s-IBM).

    Science.gov (United States)

    Acharya, Sourya; Shukla, Samarth; Kitey, Pritum; Khan, Shameem; Mahajan, S N

    2016-01-01

    Sporadic inclusion body myositis (s-IBM) is an acquired inflammatory myopathy. Clinical presentation is variable. The usual presentation is progressive weakness and atrophy of the arms and leg muscles, especially of the quadriceps femoris which is invariably affected. It is classified under inflammatory myopathies, along with polymyositis and dermatomyositis. We present a case of s-IBM who presented with gradually progressive quadriparesis with characteristic quadriceps wasting and weakness in neck flexors. Electromyography revealed myopathic potential and muscle biopsy revealed features of inclusion body myositis.

  3. Adult Niemann-Pick disease type B with myositis ossificans: a case report

    Directory of Open Access Journals (Sweden)

    Russka Shumnalieva

    2016-07-01

    Full Text Available Niemann-Pick Disease (NPD is a rare autosomal recessive lysosomal lipid storage disorder. The disease is caused by gene mutations that affect the metabolism of sphingolipids. The dysfunctions cause sphingomyelin to accumulate in different organs. NPD includes forms with low and high levels of sphingomyelin. We report a case of a 34 year-old man with a family history of NPD type B who presented with hepatosplenomegaly, neurological deficiency, bone abnormalities, and myositis ossificans. The clinical, biochemical, and imaging data confirmed the combined diagnosis of NPD type B with myositis ossificans.

  4. Fatal Tuberculous Myositis in an Immunocompromised Adult With Primary Sjögren's Syndrome

    Directory of Open Access Journals (Sweden)

    Chi-Chang Huang

    2010-09-01

    Full Text Available Tuberculous myositis, which mimics rheumatic symptoms, is an extremely rare disease. Clinical ambiguity easily leads to misdiagnosis and delayed initial treatment. We present the case of a 55-year-old man who had primary Sjögren's syndrome and active cutaneous vasculitis treated with steroid and immunosuppressive drugs. He presented with a swollen, painful, hot left thigh. Although anti-tuberculosis medications were administered soon after a positive acid-fast stain of incisional muscular tissue, he died of rapidly progressive tuberculous myositis and multiorgan failure following 18 days of hospitalization. This case is presented to increase the awareness of this rare entity in clinical practice.

  5. Outcome of allogeneic hematopoietic stem cell transplantation for childhood acute lymphoblastic leukemia in second complete remission: a single institution study

    Directory of Open Access Journals (Sweden)

    Eun-Jung Lee

    2012-03-01

    Full Text Available Purpose : The survival rate for childhood acute lymphoblastic leukemia (ALL has improved significantly. However, overall prognosis for the 20 to 25% of patients who relapse is poor, and allogeneic hematopoietic stem cell transplantation (HSCT offers the best chance for cure. In this study, we identified significant prognostic variables by analyzing the outcomes of allogeneic HSCT in ALL patients in second complete remission (CR. Methods : Fifty-three ALL patients (42 men, 79% who received HSCT in second CR from August 1991 to February 2009 were included (26 sibling donor HSCTs, 49%; 42 bone marrow transplantations, 79%. Study endpoints included cumulative incidence of acute and chronic graft-versus-host disease (GVHD, relapse, 1-year transplant-related mortality (TRM, disease-free survival (DFS, and overall survival (OS. Results : Cumulative incidences of acute GVHD (grade 2 or above and chronic GVHD were 45.3% and 28.5%, respectively. The estimated 5-year DFS and OS for the cohort was 45.2¡?#?.8%; and 48.3¡?#?%,; respectively. Only donor type, i.e., sibling versus unrelated, showed significant correlation with DFS in multivariate analysis (P=0.010. The rates of relapse and 1 year TRM were 28.9¡?#?.4%; and 26.4¡?#?.1%;, respectively, and unrelated donor HSCT (P=0.002 and HLA mismatch (P =0.022 were significantly correlated with increased TRM in univariate analysis. Conclusion : In this single institution study spanning more than 17 years, sibling donor HSCT was the only factor predicting a favorable result in multivariate analysis, possibly due to increased TRM resulting from unrelated donor HSCT.

  6. Endocrine Effects of the Treatment for Acute Lymphoblastic Leukemia and Hodgkin’s Lymphoma in Childhood

    NARCIS (Netherlands)

    R.D. van Beek (Robert Diederik)

    2010-01-01

    textabstractOne quarter of all cases of pediatric malignancies is acute Lymphoblastic leukemia (ALL). Per year approximately 4 in 100.000 children are diagnosed with ALL. The disease has a peak incidence between the third and sixth year of life. Predisposing factors for ALL are Down syndrome,

  7. Lactobacillus GG for treatment of acute childhood diarrhoea: an open labelled, randomized controlled trial.

    Science.gov (United States)

    Aggarwal, Sunny; Upadhyay, Amit; Shah, Dheeraj; Teotia, Neeraj; Agarwal, Astha; Jaiswal, Vijay

    2014-03-01

    Randomized controlled trials in developed countries have reported benefits of Lactobacillus GG (LGG) in the treatment of acute watery diarrhoea, but there is paucity of such data from India. The study was aimed to evaluate the efficacy and safety of Lactobacillus GG in the treatment of acute diarrhoea in children from a semi-urban city in north India. In this open labelled, randomized controlled trial 2000 children with acute watery diarrhoea, aged between 6 months to 5 years visiting outpatient department and emergency room of a teaching hospital in north India were enrolled. The children were randomized into receiving either Lactobacillus GG in dose of 10 billion cfu/day for five days or no probiotic medication in addition to standard WHO management of diarrhoea. Primary outcomes were duration of diarrhoea and time to change in consistency of stools. Median (inter quartile range) duration of diarrhoea was significantly shorter in children in LGG group [60 (54-72) h vs. 78 (72-90) h; PLactobacillus GG than control group [36 (30-36) h vs. 42 (36-48) h; PLactobacillus GG in children with acute diarrhoea resulted in shorter duration and faster improvement in stool consistency as compared to the control group.

  8. Acute Childhood Cardiorenal Syndrome and Impact of Cardiovascular Morbidity on Survival

    Directory of Open Access Journals (Sweden)

    Wasiu A. Olowu

    2011-01-01

    Full Text Available Cardiorenal syndrome (CRS clinical types, prevalence, aetiology, and acute cardiovascular morbidity impact on the outcome of acute kidney function perturbation were determined. Forty-seven of 101 (46.53% patients with perturbed kidney function had CRS. Types 3 and 5 CRS were found in 10 and 37 patients, respectively. Type 3 CRS was due to acute glomerulonephritis (AGN; =7, captopril (=1, frusemide (=1, and hypovolaemia (=1. Malaria-associated haemoglobinuria (=20, septicaemia (=11, lupus nephritis (=3, tumour lysis syndrome (=2, and acute lymphoblastic leukaemia (=1 caused Type 5 CRS. The cumulative mortality in hypertensive CRS was similar to nonhypertensive CRS (51.4% versus 40.9%; =.119. Mortality in CRS and non-CRS was similar (45.7% versus 24.5%; =.053. Type 5 survived better than type 3 CRS (66.7% versus 12.5%; =.001. Risk factors for mortality were Type 3 CRS (=.001, AGN-associated CRS (=.023, dialysis requiring CRS (=.008, and heart failure due to causes other than anaemia (=.003. All-cause-mortality was 34.2%. Preventive measures aimed at the preventable CRS aetiologies might be critical to reducing its prevalence.

  9. Consensus definitions of 14 severe acute toxic effects for childhood lymphoblastic leukaemia treatment

    DEFF Research Database (Denmark)

    Schmiegelow, K.; Attarbaschi, Andishe; Barzilai, Shlomit

    2016-01-01

    Although there are high survival rates for children with acute lymphoblastic leukaemia, their outcome is often counterbalanced by the burden of toxic effects. This is because reported frequencies vary widely across studies, partly because of diverse definitions of toxic effects. Using the Delphi ...

  10. Heterogeneous cytogenetic subgroups and outcomes in childhood acute megakaryoblastic leukemia: A retrospective international study

    NARCIS (Netherlands)

    H. Inaba (Hiroto); Y. Zhou (Yinmei); O. Abla (Oussama); S. Adachi (Susumu); A. Auvrignon (Anne); H.B. Beverloo (Berna); E.S.J.M. de Bont (Eveline); T.-T. Chang (Tai-Tsung); U. Creutzig; M.N. Dworzak (Michael); S. Elitzur (Sarah); A. Fynn (Alcira); E. Forestier (Erik); H. Hasle (Henrik); D.-C. Liang (Der-Cherng); V. Lee (Vincent); F. Locatelli (Franco); R. Masetti (Riccardo); B. de Moerloose (Barbara); D. Reinhardt (Dirk); L. Rodriguez (Laura); N. van Roy (Nadine); S. Shen (Shuhong); T. Taga (Takashi); D. Tomizawa (Daisuke); A.E.J. Yeoh (Allen E. J.); M. Zimmermann (Martin); S.C. Raimondi (Susana)

    2015-01-01

    textabstractComprehensive clinical studies of patients with acute megakaryoblastic leukemia (AMKL) are lacking. We performed an international retrospective study on 490 patients (age ≤18 years) with non-Down syndrome de novo AMKL diagnosed from 1989 to 2009. Patients with AMKL (median age 1.53

  11. Hyperglycemia during induction therapy is associated with increased infectious complications in childhood acute lymphocytic leukemia

    Science.gov (United States)

    Children with acute lymphocytic leukemia (ALL) are at high risk for developing hyperglycemia. Hyperglycemic adult ALL patients have shorter remissions, more infections, and increased mortality. No corresponding data are available in children. We hypothesized that children with ALL who become hypergl...

  12. Fine motor and handwriting problems after treatment for childhood acute lymphoblastic leukemia

    NARCIS (Netherlands)

    ReindersMesselink, HA; Schoemaker, MM; Hofte, M; Goeken, LNH; Kingma, A; vandenBriel, MM; Kamps, WA

    1996-01-01

    Motor skills were investigated in 18 children 2 years after treatment for acute lymphoblastic leukemia (ALL). Cross and fine motor functioning were examined with the Movement Assessment Battery for Children. Handwriting as a specific fine motor skill was studied with a computerized writing task. We

  13. Prediction of immunophenotype, treatment response, and relapse in childhood acute lymphoblastic leukemia using DNA microarrays

    DEFF Research Database (Denmark)

    Willenbrock, Hanni; Juncker, Agnieszka; Schmiegelow, K.

    2004-01-01

    Gene expression profiling is a promising tool for classification of pediatric acute lymphoblastic leukemia ( ALL). We analyzed the gene expression at the time of diagnosis for 45 Danish children with ALL. The prediction of 5-year event-free survival or relapse after treatment by NOPHO-ALL92 or 2000...

  14. Childhood Acute Lymphoblastic Leukemia Treatment (PDQ®)—Health Professional Version

    Science.gov (United States)

    For acute lymphoblastic leukemia (ALL), the 5-year survival rate has improved significantly since 1975. Get information about risk factors, signs, diagnosis, molecular features, survival, risk-based treatment assignment, and induction and postinduction therapy for children and adolescents with newly diagnosed and recurrent ALL.

  15. Measures of 6-mercaptopurine and methotrexate maintenance therapy intensity in childhood acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Nielsen, Stine Nygaard; Grell, Kathrine; Nersting, Jacob

    2016-01-01

    PURPOSE: Normal white blood cell counts (WBC) are unknown in children with acute lymphoblastic leukemia (ALL). Accordingly, 6-mercaptopurine (6MP) and methotrexate (MTX) maintenance therapy is adjusted by a common WBC target of 1.5-3.0 × 10(9)/L. Consequently, the absolute degree...

  16. Pubertal development and fertility in survivors of childhood acute myeloid leukemia treated with chemotherapy only

    DEFF Research Database (Denmark)

    Molgaard-Hansen, Lene; Skou, Anne-Sofie; Juul, Anders

    2013-01-01

    More than 60% of children with acute myeloid leukemia (AML) become long-term survivors. Most are cured using chemotherapy without hematopoietic stem cell transplantation (HSCT). We report on pubertal development and compare self-reported parenthood among AML survivors and their siblings....

  17. Granulocytic Sarcoma as the First Sign of Acute Leukemia in Childhood

    Directory of Open Access Journals (Sweden)

    Aalia R Sufi

    2012-01-01

    Full Text Available Acute myeloid leukemia (AML may rarely involve the orbit as a solid tumor termed granulocytic sarcoma. This report describes the case of a child who presented with rapidly progressive unilateral proptosis and was diagnosed as rhabdomyosarcoma. However subsequent examination of the peripheral blood film revealed AML. Thus proptosis may present as the initial manifestation of AML.

  18. Chemotherapy-Related Side Effects in Childhood Acute Lymphoblastic Leukemia in Indonesia: Parental Perceptions

    NARCIS (Netherlands)

    Sitaresmi, M.N.; Mostert, S.; Purwanto, I.; Gundy, C.; Sutaryo, N.N.; Veerman, A.J.P.

    2009-01-01

    Noncompliance with prescribed medication has been associated with increased chance of relapse and poor outcome. Side effects may be an important cause of noncompliance. Fifty-one parents of children with acute lymphoblastic leukemia in a tertiary care hospital in Indonesia were interviewed about

  19. Expression of multidrug resistance-associated proteins predicts prognosis in childhood and adult acute lymphoblastic leukemia

    NARCIS (Netherlands)

    Plasschaert, SLA; de Bont, ESJM; Boezen, M; vander Kolk, DM; Daenen, SMJG; Faber, KN; Kamps, WA; de Vries, EGE; Vellenga, E

    2005-01-01

    PURPOSE: Patients with acute lymphoblastic leukemia (ALL) are treated with a variety of chemotherapeutic drugs, which can be transported by six multidrug resistance-associated proteins (MRP). These MRPs have strongly overlapping functional activities. The aim of this study was to investigate the

  20. Screening for Acute Childhood Malnutrition during the National Nutrition Week in Mali Increases Treatment Referrals

    Science.gov (United States)

    Nyirandutiye, Daniele H.; Ag Iknane, Akory; Fofana, Amadou; Brown, Kenneth H.

    2011-01-01

    Objective To evaluate a pilot intervention designed to integrate mid-upper arm circumference (MUAC) screening for acute malnutrition into the semi-annual Child Nutrition Week (Semaine d'Intensification des Activités de Nutrition, or “SIAN”) activities carried out in June 2008. Design A cross-sectional survey was conducted in Kolokani and Nara, two health districts in the Koulikoro region of Mali, 4–5 months after the SIAN, using a population-proportionate, multi-stage random sample of: 1) health centers, and 2) households in communities linked to each of the selected health centers. Caregivers of 1543 children who were 6–59 months of age at the time of the SIAN, 17 community-based volunteers and 45 health center staff members were interviewed. Results A total of 1278 children 6–59 months (83% of those studied) reportedly participated in SIAN. Of the participating children, 1258 received vitamin A (98% of SIAN participants; 82% of all eligible children), 945 received anti-helminth tablets (84% of participants; 71% of eligibles), and 669 were screened for acute malnutrition (52% of participants; 43% of eligibles). 186 of the children screened (27%) were reportedly identified as acutely malnourished. SIAN screening covered a significantly greater proportion of children than were examined in both community-based (22% of children) and health center-based screening activities (5% of children) combined during the 4-5 months after the SIAN (P<0.0001). In general, community volunteers and health personnel positively evaluated their experience adding MUAC screening to SIAN. Conclusion Integrating MUAC screening for acute malnutrition in SIAN permits the assessment of a large number of children for acute malnutrition, and should be continued. PMID:21731602

  1. [microRNA expression in childhood acute granulocytic leukemia and its subtypes].

    Science.gov (United States)

    Luo, Xue-qun; Xu, Ling; Ke, Zhi-yong; Huang, Li-bin; Zhang, Xiao-li; Zhang, Li-dan

    2011-11-01

    Recent studies have suggested that there is a close relation between microRNA and acute leukemia (AL). The aim of this study was to investigate and better understand the classification and diagnosis of AL as well as pathogenesis and prognosis of this disease. A total of 93 children with AL and and 12 cases of idiopathic thrombocytopenic purpura (as control group) were enrolled in this study. Microarray chip analysis of their bone marrow samples was conducted to evaluate the microRNA profiles. Quantitative real-time PCR was performed for validating the abnormal expression of microRNA. The microRNA expression profiles were different between acute granulocytic leukemia and acute lymphoblastic leukemia and also between the three subtypes (M1, M2 and M3) of acute granulocytic leukemia according to FAB classification based on leukemic cell differentiation. These three subtypes of leukemia could be identified by unsupervised hierarchical cluster analysis of microRNA expression and had specific up-regulation of miR-335, miR-126 and miR-125b, respectively. However, in the M2 and M3 subtypes with positive AML1-ETO and PML-RARα, respectively, which have a better prognosis, the expressions of miR-126 and miR-125b were significantly higher than those with negative AML1-ETO and PML-RARα. Further more, miR-335 and miR-146 were up-regulated in acute granulocytic leukemia observed in this study, which are different from those reported for adult patients. microRNA cascade may serve as new biomarkers for the classification and diagnosis of pediatric AL. It is also suggested that there might be different pathogenesis and prognosis between AL types related to specific expression and regulation of microRNA.

  2. Asparaginase-associated pancreatitis in childhood acute lymphoblastic leukaemia: an observational Ponte di Legno Toxicity Working Group study.

    Science.gov (United States)

    Wolthers, Benjamin O; Frandsen, Thomas L; Baruchel, André; Attarbaschi, Andishe; Barzilai, Shlomit; Colombini, Antonella; Escherich, Gabriele; Grell, Kathrine; Inaba, Hiroto; Kovacs, Gábor; Liang, Der-Cherng; Mateos, Marion; Mondelaers, Veerle; Möricke, Anja; Ociepa, Tomasz; Samarasinghe, Sujith; Silverman, Lewis B; van der Sluis, Inge M; Stanulla, Martin; Vrooman, Lynda M; Yano, Michihiro; Zapotocka, Ester; Schmiegelow, Kjeld

    2017-09-01

    Survival for childhood acute lymphoblastic leukaemia surpasses 90% with contemporary therapy; however, patients remain burdened by the severe toxic effects of treatment, including asparaginase-associated pancreatitis. To investigate the risk of complications and risk of re-exposing patients with asparaginase-associated pancreatitis to asparaginase, 18 acute lymphoblastic leukaemia trial groups merged data for this observational study. Patient files from 26 trials run by 18 trial groups were reviewed on children (aged 1·0-17·9 years) diagnosed with t(9;22)-negative acute lymphoblastic leukaemia between June 1, 1996, and Jan 1, 2016, who within 50 days of asparaginase exposure developed asparaginase-associated pancreatitis. Asparaginase-associated pancreatitis was defined by at least two criteria: abdominal pain, pancreatic enzymes at least three times the upper limit of normal (ULN), and imaging compatible with pancreatitis. Patients without sufficient data for diagnostic criteria were excluded. Primary outcomes were defined as acute and persisting complications of asparaginase-associated pancreatitis and risk of re-exposing patients who suffered an episode of asparaginase-associated pancreatitis to asparaginase. Data were collected from Feb 2, 2015, to June 30, 2016, and analysed and stored in a common database at Rigshospitalet, Copenhagen, Denmark. Of 465 patients with asparaginase-associated pancreatitis, 33 (8%) of 424 with available data needed mechanical ventilation, 109 (26%) of 422 developed pseudocysts, acute insulin therapy was needed in 81 (21%) of 393, and seven (2%) of 458 patients died. Risk of assisted mechanical ventilation, need for insulin, pseudocysts, or death was associated with older age (median age for patients with complications 10·5 years [IQR 6·4-13·8] vs without complications 6·1 years [IQR 3·6-12·2], ppancreatitis, 31 (11%) of 275 patients still needed insulin or had recurrent abdominal pain or both. Both the risk of persisting

  3. The role of ATP-binding cassette transporter A2 in childhood acute lymphoblastic leukemia multidrug resistance

    Science.gov (United States)

    Aberuyi, N; Rahgozar, S; Moafi, A

    2014-01-01

    Acute lymphoblastic leukemia (ALL) is one of the most prevalent hematologic malignancies in children. Although the cure rate of ALL has improved over the past decades, the most important reason for ALL treatment failure is multidrug resistance (MDR) phenomenon. The current study aims to explain the mechanisms involved in multidrug resistance of childhood ALL, and introduces ATP-binding cassette transporterA2 (ABCA2) as an ABC transporter gene which may have a high impact on MDR. Benefiting from articles published inreputable journals from1994 to date and experiments newly performed by our group, a comprehensive review is written about ABCA2 and its role in MDR regarding childhood ALL. ABCA2 transports drugs from the cytoplasm into the lysosomal compartment, where they may become degraded and exported from the cell. The aforementioned mechanism may contribute to MDR. It has been reported that ABCA2 may induce resistance to mitoxantrone, estrogen derivatives and estramustine. It is resistant to the aforementioned compounds. Furthermore, the overexpression ofABCA2 in methotrexate, vinblastine and/or doxorubicin treated Jurkat cells are observed in several publications. The recent study of our group showsthatthe overexpression ofABCA2 gene in children with ALL increases the risk of MDR by 15 times. ABCA2 is the second identified member of the ABCA; ABC transporters' subfamily. ABCA2 gene expression profile is suggested to be an unfavorable prognostic factor in ALL treatment. Better understanding of the MDR mechanisms and the factors involved may improve the therapeutic outcome of ALL by modifying the treatment protocols. PMID:25254091

  4. Residential Exposure to Natural Background Radiation and Risk of Childhood Acute Leukemia in France, 1990-2009.

    Science.gov (United States)

    Demoury, Claire; Marquant, Fabienne; Ielsch, Géraldine; Goujon, Stéphanie; Debayle, Christophe; Faure, Laure; Coste, Astrid; Laurent, Olivier; Guillevic, Jérôme; Laurier, Dominique; Hémon, Denis; Clavel, Jacqueline

    2017-04-01

    Exposures to high-dose ionizing radiation and high-dose rate ionizing radiation are established risk factors for childhood acute leukemia (AL). The risk of AL following exposure to lower doses due to natural background radiation (NBR) has yet to be conclusively determined. AL cases diagnosed over 1990-2009 (9,056 cases) were identified and their municipality of residence at diagnosis collected by the National Registry of Childhood Cancers. The Geocap study, which included the 2,763 cases in 2002-2007 and 30,000 population controls, was used for complementary analyses. NBR exposures were modeled on a fine scale (36,326 municipalities) based on measurement campaigns and geological data. The power to detect an association between AL and dose to the red bone marrow (RBM) fitting UNSCEAR (United Nations Scientific Committee on the Effects of Atomic Radiation) predictions was 92%, 45% and 99% for exposure to natural gamma radiation, radon and total radiation, respectively. AL risk, irrespective of subtype and age group, was not associated with the exposure of municipalities to radon or gamma radiation in terms of yearly exposure at age reached, cumulative exposure or RBM dose. There was no confounding effect of census-based socio-demographic indicators, or environmental factors (road traffic, high voltage power lines, vicinity of nuclear plants) related to AL in the Geocap study. Our findings do not support the hypothesis that residential exposure to NBR increases the risk of AL, despite the large size of the study, fine scale exposure estimates and wide range of exposures over France. However, our results at the time of diagnosis do not rule out a slight association with gamma radiation at the time of birth, which would be more in line with the recent findings in the UK and Switzerland.

  5. Evaluation of memory impairment in aging adult survivors of childhood acute lymphoblastic leukemia treated with cranial radiotherapy.

    Science.gov (United States)

    Armstrong, Gregory T; Reddick, Wilburn E; Petersen, Ronald C; Santucci, Aimee; Zhang, Nan; Srivastava, Deokumar; Ogg, Robert J; Hillenbrand, Claudia M; Sabin, Noah; Krasin, Matthew J; Kun, Larry; Pui, Ching-Hon; Hudson, Melissa M; Robison, Leslie L; Krull, Kevin R

    2013-06-19

    Cranial radiotherapy (CRT) is a known risk factor for neurocognitive impairment in survivors of childhood cancer and may increase risk for mild cognitive impairment and dementia in adulthood. We performed a cross-sectional evaluation of survivors of childhood acute lymphoblastic leukemia (ALL) treated with 18 Gy (n = 127) or 24 Gy (n = 138) CRT. Impairment (age-adjusted score >1 standard deviation below expected mean, two-sided exact binomial test) on the Wechsler Memory Scale IV (WMS-IV) was measured. A subset of survivors (n = 85) completed structural and functional neuroimaging. Survivors who received 24 Gy, but not 18 Gy, CRT had impairment in immediate (impairment rate = 33.8%, 95% confidence interval [CI] = 25.9% to 42.4%; P memory (impairment rate = 30.2%, 95% CI = 22.6% to 38.6%; P memory among survivors who received 24 Gy CRT was equivalent to that for individuals older than 69 years. Impaired immediate memory was associated with smaller right (P = .02) and left (P = .008) temporal lobe volumes, and impaired delayed memory was associated with thinner parietal and frontal cortices. Lower hippocampal volumes and increased functional magnetic resonance imaging activation were observed with memory impairment. Reduced cognitive status (Brief Cognitive Status Exam from the WMS-IV) was identified after 24 Gy (18.5%, 95% CI = 12.4% to 26.1%; P Adult survivors who received 24 Gy CRT had reduced cognitive status and memory, with reduced integrity in neuroanatomical regions essential in memory formation, consistent with early onset mild cognitive impairment.

  6. Severe acute malnutrition in childhood: hormonal and metabolic status at presentation, response to treatment, and predictors of mortality.

    Science.gov (United States)

    Bartz, Sarah; Mody, Aaloke; Hornik, Christoph; Bain, James; Muehlbauer, Michael; Kiyimba, Tonny; Kiboneka, Elizabeth; Stevens, Robert; Bartlett, John; St Peter, John V; Newgard, Christopher B; Freemark, Michael

    2014-06-01

    Malnutrition is a major cause of childhood morbidity and mortality. To identify and target those at highest risk, there is a critical need to characterize biomarkers that predict complications prior to and during treatment. We used targeted and nontargeted metabolomic analysis to characterize changes in a broad array of hormones, cytokines, growth factors, and metabolites during treatment of severe childhood malnutrition. Children aged 6 months to 5 years were studied at presentation to Mulago Hospital and during inpatient therapy with milk-based formulas and outpatient supplementation with ready-to-use food. We assessed the relationship between baseline hormone and metabolite levels and subsequent mortality. Seventy-seven patients were enrolled in the study; a subset was followed up from inpatient treatment to the outpatient clinic. Inpatient and outpatient therapies increased weight/height z scores and induced striking changes in the levels of fatty acids, amino acids, acylcarnitines, inflammatory cytokines, and various hormones including leptin, insulin, GH, ghrelin, cortisol, IGF-I, glucagon-like peptide-1, and peptide YY. A total of 12.2% of the patients died during hospitalization; the major biochemical factor predicting mortality was a low level of leptin (P = .0002), a marker of adipose tissue reserve and a critical modulator of immune function. We have used metabolomic analysis to provide a comprehensive hormonal and metabolic profile of severely malnourished children at presentation and during nutritional rehabilitation. Our findings suggest that fatty acid metabolism plays a central role in the adaptation to acute malnutrition and that low levels of the adipose tissue hormone leptin associate with, and may predict, mortality prior to and during treatment.

  7. Long-Term Effect of Cranial Radiotherapy on Pituitary-Hypothalamus Area in Childhood Acute Lymphoblastic Leukemia Survivors.

    Science.gov (United States)

    Follin, Cecilia; Erfurth, Eva Marie

    2016-09-01

    Survival rates of childhood cancer have improved markedly, and today more than 80 % of those diagnosed with a pediatric malignancy will become 5-year survivors. Nevertheless, survivors exposed to cranial radiotherapy (CRT) are at particularly high risk for long-term morbidity, such as endocrine insufficiencies, metabolic complications, and cardiovascular morbidity. Deficiencies of one or more anterior pituitary hormones have been described following therapeutic CRT for primary brain tumors, nasopharyngeal tumors, and following prophylactic CRT for childhood acute lymphoblastic leukemia (ALL). Studies have consistently shown a strong correlation between the total radiation dose and the development of pituitary deficits. Further, age at treatment and also time since treatment has strong implications on pituitary hormone deficiencies. There is evidence that the hypothalamus is more radiosensitive than the pituitary and is damaged by lower doses of CRT. With doses of CRT hypothalamus and this usually causes isolated GH deficiency (GHD). Higher doses (>50 Gy) may produce direct anterior pituitary damage, which contributes to multiple pituitary deficiencies. The large group of ALL survivors treated with CRT in the 70-80-ties has now reached adulthood, and these survivors were treated mainly with 24 Gy, and the vast majority of these patients suffer from GHD. Further, after long-term follow-up, insufficiencies in prolactin (PRL) and thyroid stimulating hormone (TSH) have also been reported and a proportion of these patients were also adrenocoticotrophic hormone (ACTH) deficient. CRT to the hypothalamus causes neuroendocrine dysfunction, which means that the choice of GH test is crucial for the diagnosis of GHD.

  8. Lactobacillus GG for treatment of acute childhood diarrhoea: An open labelled, randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Sunny Aggarwal

    2014-01-01

    Full Text Available Background & objectives : 0 Randomized controlled trials in developed countries have reported benefits of Lactobacillus GG (LGG in the treatment of acute watery diarrhoea, but there is paucity of such data from India. The study was aimed to evaluate the efficacy and safety of Lactobacillus GG in the treatment of acute diarrhoea in children from a semi-urban city in north India. Methods: In this open labelled, randomized controlled trial 2000 children with acute watery diarrhoea, aged between 6 months to 5 years visiting 0 outpatient department and emergency room of a teaching hospital in north India were enrolled. The children were randomized into receiving either Lactobacillus GG in dose of 10 billion cfu/day for five days or no probiotic medication in addition to standard WHO management of diarrhoea. 0 Primary outcomes were duration of diarrhoea and time to change in consistency of stools. Results : 0 Median (inter quartile range duration of diarrhoea was significantly shorter in children in LGG group [60 (54-72 h vs. 78 (72-90 h; P<0.001]. Also, there was faster improvement in stool consistency in children receiving Lactobacillus GG than control group [36 (30-36 h vs. 42 (36-48 h; P<0.001]. There was significant reduction in average number of stools per day in LGG group (P<0.001 compared to the control group. These benefits were seen irrespective of rotavirus positivity in stool tests. Interpretation & conclusions : 0 Our results showed that the use of Lactobacillus GG in children with acute diarrhoea resulted in shorter duration and faster improvement in stool consistency as compared to the control group.

  9. Acute Motor Axonal Neuropathy (Aman) With Motor Conduction Blocks In Childhood; Case Report

    OpenAIRE

    Yildirim, Serhan; Adviye, Rah?an; G?l, Hakan Levent; T?rk B?r?, ?lk?

    2016-01-01

    Objective Acute motor axonal neuropathy (AMAN), characterized with decreased compound muscle action potentials (CMAP) and absence of demyelinating findings in electrophysiological studies, is a subtype of Guillain-Barre Syndrome (GBS). A 4 yr-old male patient presented with ascending weakness, dysarthria and dysphagia to ?stanbul Dr. L?tfi K?rdar Kartal Training and Research Hospital Neurology outpatient for three days to in 2012. Dysphonia, restricted eye movements, flaccid tetraplegia and a...

  10. Computerized psychometry screening in long-term survivors of childhood acute lymphoblastic leukemia.

    Science.gov (United States)

    O'Hare, A E; Aitken, K; Eden, O B

    1988-01-01

    This study assessed the diagnostic utility of a computerized psychometry battery of tests: the Bexley-Maudsley Automated Psychological Screening Test and Category Sorting Test in the screening for deficits in cognitive function in a population of children who had been treated for acute lymphoblastic leukemia. Central nervous system therapy with radiotherapy and intrathecal chemotherapy has been incriminated as a cause of psychological morbidity in survivors. Twenty-nine children who were surviving in their first hematological remission, following cessation of their treatment for acute lymphoblastic leukemia, were studied. No child had evidence of central nervous system leukemic involvement, and they were all attending normal schools. Their performances were compared with 29 control children matched by age, sex, and social class. The children treated for leukemia showed a reduced ability to sustain attention (p less than 0.025), a reduction in verbal recognition short term memory (p less than 0.02), and difficulties in abstract problem solving (p less than 0.01). These results confirm the presence of neurophysical morbidity in children treated for acute lymphoblastic leukemia. It is suggested that this computerized psychometry test battery is a useful method for examining children at risk of neurological impairment and identifies specific deficits that require further evaluation and remedial help.

  11. The metabolic syndrome in survivors of childhood acute lymphoblastic leukemia in Isfahan, Iran

    Science.gov (United States)

    Reisi, Nahid; Azhir, Afshin; Hashemipour, Mahin; Raeissi, Pouran; Amini, Abasgholi; Moafi, Alireza

    2009-01-01

    BACKGROUND: To determine the prevalence of metabolic syndrome in survivors of childhood leukemia in Isfahan, Iran. METHODS: During a 4-year period (2003 to 2007), 55 children (33 male and 22 female) diagnosed with ALL at Unit of Hematology/ Oncology, Department of Pediatrics, Isfahan University of Medical Science, were enrolled in this cross-sectional study. Metabolic syndrome was defined using the modified version of Adult Treatment Panel (ATP III) crite-ria. Insulin resistance was defined based on the homeostasis model assessment index (HOMA-IR). RESULTS: The mean age of participates was 10.4 years (range 6-19 years) and the mean interval since completion of chemotherapy was 35 months. Twenty percent (11/55) of survivors (10 male, 1 female) met criteria for diagnosis of metabolic syndrome. Obesity was observed in one forth of patients and nearly 3/4 of obese patients had metabolic syndrome. High serum insulin levels were found in 16% of participants and in 63% of obese survivors. The mean insulin levels in survivors with metabolic syndrome was three-times more than those without (28.3 mu/l vs. 9.57 mu/l, p = 0.004). Insulin resistance was detected in 72.7% of survivors with metabolic syndrome and it was positively correlated with serum triglycerides (0.543, p ≤ 0.001), systolic and diastolic BP (0.348, p = 0.01 and 0.368, p = 006 respectively), insulin levels (0.914, p < 0.001) and blood sugar (0.398, p = 003). CONCLUSIONS: The prevalence of metabolic syndrome in survivors of childhood leukemia in Iran is higher than developed countries. Nearly all of the obese patients had metabolic syndrome. Weight control and regular physical exercise are recommended to the survivors. PMID:21772869

  12. Epidemiological, clinical and prognostic profile of childhood acute bacterial meningitis in a resource poor setting

    Science.gov (United States)

    Kuti, Bankole Peter; Bello, Emmanuel Olasehinde; Jegede, Tolulope Opeoluwa; Olubosede, Omolayo

    2015-01-01

    Background: Childhood bacterial meningitis is a neurologic emergency that continues to kill and maims children particularly in developing countries with poor immunization coverage. Objective: This study set out to assess the hospital incidence, pattern of presentation, etiologic agents, outcome and determinants of mortality among the children admitted with bacterial meningitis at the Wesley Guild Hospital (WGH), Ilesa. Patients and Methods: We carried out a retrospective review of admitted cases of bacterial meningitis in children aged one month to 15 years at the WGH, Ilesa over a three year period by looking at the hospital records. Factors in the history and examinations were compared among survivors and those that died to determine factors significantly associated with mortality in these children. Results: Eighty-one (5.5%) of the 1470 childhood admissions during the study period had bacterial meningitis. Male preponderance was observed and two-thirds of the children were infants. More cases were admitted during the wet rainy season than during the dry harmattan season. Haemophilus influenzae type B and Streptococcus pneumoniae were the leading etiologic agents and ciprofloxacin and ceftriaxone adequately cover for these organisms. Twenty-two (27.2%) of the 81 children died, while 34 (42.0%) survived with neurologic deficits. Children with multiple seizures, coma, neck retraction, hyponatremia, hypoglycorrhachia, turbid CSF as well as Gram positive meningitis at presentation were found to more likely to die (P meningitis often results in death and neurologic deficit among infants and young children admitted at the WGH, Ilesa. Children diagnosed with meningitis who in addition had multiple seizures, neck retraction and coma at presentation are at increased risk of dying. PMID:26752902

  13. Childhood Acute Respiratory Infections and Household Environment in an Eastern Indonesian Urban Setting

    Directory of Open Access Journals (Sweden)

    Tomoyuki Shibata

    2014-11-01

    Full Text Available This pilot study evaluated the potential effect of household environmental factors such as income, maternal characteristics, and indoor air pollution on children’s respiratory status in an Eastern Indonesian community. Household data were collected from cross-sectional (n = 461 participants and preliminary childhood case-control surveys (pneumonia cases = 31 diagnosed within three months at a local health clinic; controls = 30. Particulate matter (PM2.5 and PM10 was measured in living rooms, kitchens, children’s bedrooms, and outside areas in close proximity once during the case-control household interviews (55 homes and once per hour from 6 a.m. to midnight in 11 homes. The household survey showed that children were 1.98 times (p = 0.02 more likely to have coughing symptoms indicating respiratory infection, if mothers were not the primary caregivers. More children exhibited coughing if they were not exclusively breastfed (OR = 2.18; p = 0.06 or there was a possibility that their mothers were exposed to environmental tobacco smoke during pregnancy (OR = 2.05; p = 0.08. This study suggests that household incomes and mother’s education have an indirect effect on childhood pneumonia and respiratory illness. The concentrations of PM2.5 and PM10 ranged from 0.5 to 35.7 µg/m3 and 7.7 to 575.7 µg/m3, respectively, based on grab samples. PM was significantly different between the case and control groups (p < 0.01. The study also suggests that ambient air may dilute indoor pollution, but also introduces pollution into the home from the community environment. Effective intervention programs need to be developed that consider multiple direct and indirect risk factors to protect children.

  14. Childhood Acute Respiratory Infections and Household Environment in an Eastern Indonesian Urban Setting

    Science.gov (United States)

    Shibata, Tomoyuki; Wilson, James L.; Watson, Lindsey M.; LeDuc, Alyse; Meng, Can; Ansariadi; La Ane, Ruslan; Manyullei, Syamsuar; Maidin, Alimin

    2014-01-01

    This pilot study evaluated the potential effect of household environmental factors such as income, maternal characteristics, and indoor air pollution on children’s respiratory status in an Eastern Indonesian community. Household data were collected from cross-sectional (n = 461 participants) and preliminary childhood case-control surveys (pneumonia cases = 31 diagnosed within three months at a local health clinic; controls = 30). Particulate matter (PM2.5 and PM10) was measured in living rooms, kitchens, children’s bedrooms, and outside areas in close proximity once during the case-control household interviews (55 homes) and once per hour from 6 a.m. to midnight in 11 homes. The household survey showed that children were 1.98 times (p = 0.02) more likely to have coughing symptoms indicating respiratory infection, if mothers were not the primary caregivers. More children exhibited coughing if they were not exclusively breastfed (OR = 2.18; p = 0.06) or there was a possibility that their mothers were exposed to environmental tobacco smoke during pregnancy (OR = 2.05; p = 0.08). This study suggests that household incomes and mother’s education have an indirect effect on childhood pneumonia and respiratory illness. The concentrations of PM2.5 and PM10 ranged from 0.5 to 35.7 µg/m3 and 7.7 to 575.7 µg/m3, respectively, based on grab samples. PM was significantly different between the case and control groups (p pollution, but also introduces pollution into the home from the community environment. Effective intervention programs need to be developed that consider multiple direct and indirect risk factors to protect children. PMID:25429685

  15. Levofloxacin in Preventing Infection in Young Patients With Acute Leukemia Receiving Chemotherapy or Undergoing Stem Cell Transplantation

    Science.gov (United States)

    2017-09-05

    Acute Leukemias of Ambiguous Lineage; Bacterial Infection; Diarrhea; Fungal Infection; Musculoskeletal Complications; Neutropenia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

  16. GENETIC POLYMORPHISMS OF THE FOLATE METABOLIC PATHWAY IN CHILDHOOD ACUTE LYMPHOBLASTIC LEUKEMIA. A MOLECULAR STUDY AND A PROPOSAL FOR AN INTERPRETATIVE MODEL.

    OpenAIRE

    Orioli, Elisa

    2014-01-01

    Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer accounting for 80% of childhood leukemia. The uncontrolled proliferation of lymphoid progenitors in the bone marrow and the accumulation of malignant lymphoblasts in peripheral blood characterize the disease. The molecular analysis of common genetic alterations in lymphoblastic cells has strongly contributed to the comprehension of ALL pathogenesis. Different gene polymorphisms (most of them SNPs) play an important role in...

  17. Myositis, rhabdomyolysis and compartment syndrome complicating influenza A in a child

    OpenAIRE

    Skellett, Sophie Clare; Dhesi, Rosepal

    2009-01-01

    A previously fit and healthy 8-year-old boy died following severe complications of influenza A. He developed lethargy and vomiting before presentation. On presentation to medical attention, on day 4 of his illness, he was in extremis and had extensive myositis, rhabdomyolysis, renal failure and compartment syndrome, which were resistant to supportive medical management.

  18. Myositis, rhabdomyolysis and compartment syndrome complicating influenza A in a child.

    Science.gov (United States)

    Skellett, Sophie Clare; Dhesi, Rosepal

    2009-01-01

    A previously fit and healthy 8-year-old boy died following severe complications of influenza A. He developed lethargy and vomiting before presentation. On presentation to medical attention, on day 4 of his illness, he was in extremis and had extensive myositis, rhabdomyolysis, renal failure and compartment syndrome, which were resistant to supportive medical management.

  19. Radiation-recall myositis presenting as low-back pain (2010: 4b)

    Energy Technology Data Exchange (ETDEWEB)

    Heirwegh, Geert [AZ Damiaanziekenhuis, Department of Radiology, Oostende (Belgium); University Hospital K.U. Leuven, Department of Radiology, Leuven (Belgium); Bruyeer, Eveline; Demaerel, Philippe [University Hospital K.U. Leuven, Department of Radiology, Leuven (Belgium); Renard, Marleen; Uyttebroeck, Anne [University Hospital K.U. Leuven, Department of Paediatrics, Leuven (Belgium)

    2010-07-15

    We report on a patient with a history of Ewing sarcoma who underwent surgery and subsequent adjuvant chemotherapy and radiotherapy. He developed low-back pain 6 months after the end of the radiotherapy and during consolidation chemotherapy. Magnetic resonance imaging showed evidence of myositis corresponding to the 'radiation-recall phenomenon', an inflammatory reaction of irradiated tissue. (orig.)

  20. Statin-induced focal myositis of the upper extremity. A report of two cases

    Energy Technology Data Exchange (ETDEWEB)

    Wagner, M., E-mail: wagner.radiologie@herzchirurgie.de [Department of Radiology, Herz- und Gefaessklinik GmbH, Salzburger Leite 1, D-97616 Bad Neustadt an der Saale (Germany); Muehldorfer-Fodor, M.; Prommersberger, K.J. [Department of Handsurgery, Herz- und Gefaessklinik GmbH, Bad Neustadt an der Saale (Germany); Schmitt, R. [Department of Radiology, Herz- und Gefaessklinik GmbH, Salzburger Leite 1, D-97616 Bad Neustadt an der Saale (Germany)

    2011-02-15

    Statins are widely used to lower increased cholesterol levels with the aim to prevent major cardiovascular events. However, they bare the risk of myotoxic side effects. We report on two patients with focal weakness and pain in the upper extremities. In both patients, abnormal MRI signal heights in the muscle groups involved were indicative of the final diagnosis of focal myositis during statin therapy.

  1. Efficacy of ultrasound elastography in detecting active myositis in children: can it replace MRI?

    Energy Technology Data Exchange (ETDEWEB)

    Berko, Netanel S.; Levin, Terry L. [Montefiore Medical Center, Department of Radiology, Bronx, NY (United States); Hay, Arielle [Montefiore Medical Center, Department of Pediatrics, Division of Pediatric Rheumatology, Bronx, NY (United States); Miami Children' s Hospital, Department of Pediatrics, Miami, FL (United States); Sterba, Yonit; Wahezi, Dawn [Montefiore Medical Center, Department of Pediatrics, Division of Pediatric Rheumatology, Bronx, NY (United States)

    2015-09-15

    Juvenile idiopathic inflammatory myopathy is a rare yet potentially debilitating condition. MRI is used both for diagnosis and to assess response to treatment. No study has evaluated the performance of US elastography in the diagnosis of this condition in children. To assess the performance of compression-strain US elastography in detecting active myositis in children with clinically confirmed juvenile idiopathic inflammatory myopathy and to compare its efficacy to MRI. Children with juvenile idiopathic inflammatory myopathy underwent non-contrast MR imaging as well as compression-strain US elastography of the quadriceps muscles. Imaging findings from both modalities were compared to each other as well as to the clinical determination of active disease based on physical examination and laboratory data. Active myositis on MR was defined as increased muscle signal on T2-weighted images. Elastography images were defined as normal or abnormal based on a previously published numerical scale of muscle elastography in normal children. Muscle echogenicity was graded as normal or abnormal based on gray-scale sonographic images. Twenty-one studies were conducted in 18 pediatric patients (15 female, 3 male; age range 3-19 years). Active myositis was present on MRI in ten cases. There was a significant association between abnormal MRI and clinically active disease (P = 0.012). US elastography was abnormal in 4 of 10 cases with abnormal MRI and in 4 of 11 cases with normal MRI. There was no association between abnormal elastography and either MRI (P > 0.999) or clinically active disease (P > 0.999). Muscle echogenicity was normal in 11 patients; all 11 had normal elastography. Of the ten patients with increased muscle echogenicity, eight had abnormal elastography. There was a significant association between muscle echogenicity and US elastography (P < 0.001). The positive and negative predictive values for elastography in the determination of active myositis were 75% and 31

  2. ATF5 polymorphisms influence ATF function and response to treatment in children with childhood acute lymphoblastic leukemia.

    Science.gov (United States)

    Rousseau, Julie; Gagné, Vincent; Labuda, Malgorzata; Beaubois, Cyrielle; Sinnett, Daniel; Laverdière, Caroline; Moghrabi, Albert; Sallan, Stephen E; Silverman, Lewis B; Neuberg, Donna; Kutok, Jeffery L; Krajinovic, Maja

    2011-11-24

    Asparaginase is a standard and critical component in the therapy of childhood acute lymphoblastic leukemia. Asparagine synthetase (ASNS) and the basic region leucine zipper activating transcription factor 5 (ATF5) and arginosuccinate synthase 1 (ASS1) have been shown to mediate the antileukemic effect of asparaginase and to display variable expression between leukemia cells that are resistant and sensitive to treatment. Fourteen polymorphisms in the regulatory and coding regions of these genes were investigated for an association with acute lymphoblastic leukemia outcome. Lower event-free survival (EFS) was associated with ATF5 T1562C, tandem-repeat ASNS polymorphism, derived haplotype, and ASS1 G1343T and G34T substitutions (P ≤ .03). Associations were limited to patients who received Escherichia coli asparaginase. Variations that sustained correction for multiple testing (ATF5 T1562C, P = .005; ASNS tandem-repeat and related haplotype, P ≤ .01) were subsequently analyzed in the replication cohort. The E coli-dependent association of the ATF5 T1562 allele with reduced EFS was confirmed (P = .01). A gene-reporter assay showed that the haplotype tagged by T1562 had higher promoter activity (P ≤ .01). The remaining regulatory polymorphisms also appeared to affect ATF5 function; 2 additional high-activity haplotypes were identified (P ≤ .02) and were further corroborated by quantitative mRNA analysis in lymphoblastoid cell lines. The ATF5-regulated increase in ASNS expression in response to more efficacious E coli-induced asparagine depletion may explain our observed results.

  3. Seizure characteristics of epilepsy in childhood after acute encephalopathy with biphasic seizures and late reduced diffusion.

    Science.gov (United States)

    Ito, Yuji; Natsume, Jun; Kidokoro, Hiroyuki; Ishihara, Naoko; Azuma, Yoshiteru; Tsuji, Takeshi; Okumura, Akihisa; Kubota, Tetsuo; Ando, Naoki; Saitoh, Shinji; Miura, Kiyokuni; Negoro, Tamiko; Watanabe, Kazuyoshi; Kojima, Seiji

    2015-08-01

    The aim of this study was to clarify characteristics of post-encephalopathic epilepsy (PEE) in children after acute encephalopathy with biphasic seizures and late reduced diffusion (AESD), paying particular attention to precise diagnosis of seizure types. Among 262 children with acute encephalopathy/encephalitis registered in a database of the Tokai Pediatric Neurology Society between 2005 and 2012, 44 were diagnosed with AESD according to the clinical course and magnetic resonance imaging (MRI) findings and were included in this study. Medical records were reviewed to investigate clinical data, MRI findings, neurologic outcomes, and presence or absence of PEE. Seizure types of PEE were determined by both clinical observation by pediatric neurologists and ictal video-electroencephalography (EEG) recordings. Of the 44 patients after AESD, 10 (23%) had PEE. The period between the onset of encephalopathy and PEE ranged from 2 to 39 months (median 8.5 months). Cognitive impairment was more severe in patients with PEE than in those without. Biphasic seizures and status epilepticus during the acute phase of encephalopathy did not influence the risk of PEE. The most common seizure type of PEE on clinical observation was focal seizures (n = 5), followed by epileptic spasms (n = 4), myoclonic seizures (n = 3), and tonic seizures (n = 2). In six patients with PEE, seizures were induced by sudden unexpected sounds. Seizure types confirmed by ictal video-EEG recordings were epileptic spasms and focal seizures with frontal onset, and all focal seizures were startle seizures induced by sudden acoustic stimulation. Intractable daily seizures remain in six patients with PEE. We demonstrate seizure characteristics of PEE in children after AESD. Epileptic spasms and startle focal seizures are common seizure types. The specific seizure types may be determined by the pattern of diffuse subcortical white matter injury in AESD and age-dependent reorganization of the brain

  4. A t (9;11 translocation in childhood acute mixed leukemia

    Directory of Open Access Journals (Sweden)

    Maria de Lourdes Lopes Ferrari Chauffaille

    Full Text Available We present the case of a child with acute lymphoid leukemia (ALL who was morphologically classified as FAB L1 (PAS and peroxidase were negative. Remission was achieved with an ALL-type protocol (GBTLI. Five months after the discontinuation of therapy, the patient presented mixed leukemia (CD10, CD19, CD13 and CD33 were positive with t (9;11 (p21;q23 translocation. Unfortunately, as cytogenetic and immunophenotype studies were not performed at diagnosis, two possibilities could be considered for the relapse; secondary mixed leukemia with clonal chromosome changes, or mixed leukemia from the beginning.

  5. Severe hypercalcemia: a rare and unusual presentation of childhood acute lymphoblastic leukemia.

    Science.gov (United States)

    Bahoush, Gholamreza; Miri-Aliabad, Ghasem

    2014-01-01

    Hypercalcemia in children is a medical emergency and often manifests as nonspecific symptoms such as nausea, vomiting, weight loss, and anorexia. Severe hypercalcemia is a rare complication of malignancy in children, while it can be seen in various types of malignant tumors. It is usually associated with significant morbidity and may be severe enough to threaten life. Incidence of hypercalcemia in hematopoietic malignancies including acute lymphoblastic leukemia (ALL) is very rare and unusual, especially as the initial manifestation of the disease. In this paper a 6-year-old boy who had severe hypercalcemia and gastrointestinal symptoms before the onset of common and usual manifestations of ALL is introduced.

  6. HA-1 T TCR T Cell Immunotherapy for the Treating of Patients With Relapsed or Refractory Acute Leukemia After Donor Stem Cell Transplant

    Science.gov (United States)

    2017-11-14

    Acute Biphenotypic Leukemia in Relapse (Diagnosis); Acute Undifferentiated Leukemia in Relapse (Diagnosis); HLA-A*0201 HA-1 Positive Cells Present; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Refractory Acute Myeloid Leukemia; Refractory Adult Acute Lymphoblastic Leukemia; Refractory Childhood Acute Lymphoblastic Leukemia; Refractory Childhood Acute Myeloid Leukemia

  7. Inherited GATA3 variants are associated with Ph-like childhood acute lymphoblastic leukemia and risk of relapse

    Science.gov (United States)

    Perez-Andreu, Virginia; Roberts, Kathryn G.; Harvey, Richard C.; Yang, Wenjian; Cheng, Cheng; Pei, Deqing; Xu, Heng; Gastier-Foster, Julie; Shuyu, E; Yew-Suang Lim, Joshua; Chen, I-Ming; Fan, Yiping; Devidsa, Meenakshi; Borowitz, Michael J.; Smith, Colton; Neale, Geoffrey; Burchard, Esteban G.; Torgerson, Dara G.; Klussmann, Federico Antillon; Villagran, Cesar Rolando Najera; Winick, Naomi J.; Camitta, Bruce M.; Raetz, Elizabeth; Wood, Brent; Yue, Feng; Carroll, William L.; Larsen, Eric; Bowman, W. Paul; Loh, Mignon L.; Dean, Michael; Bhojwani, Deepa; Pui, Ching-Hon; Evans, William E.; Relling, Mary V.; Hunger, Stephen P.; Willman, Cheryl L.; Mullighan, Charles G.; Yang, Jun J.

    2014-01-01

    Recent genomic profiling of childhood acute lymphoblastic leukemia (ALL) identified a novel high-risk subtype with a gene expression signature resembling Philadelphia chromosome-positive ALL and a poor prognosis (Ph-like ALL). However, the role of inherited genetic variation in Ph-like ALL pathogenesis remains unknown. In a genome-wide association study (GWAS) of 511 ALL cases and 6,661 non-ALL controls, we identified a single susceptibility locus for Ph-like ALL (GATA3, rs3824662, P=2.17×10−14, odds ratio [OR]=3.85, for Ph-like ALL vs. non-ALL; P=1.05×10−8, OR=3.25, for Ph-like ALL vs. non-Ph-like ALL) that was independently validated. The rs3824662 risk allele was associated with somatic lesions underlying Ph-like ALL (i.e., CRLF2 rearrangement, JAK mutation, and IKZF1 deletion) and directly influenced GATA3 transcription. Finally, GATA3 SNP genotype was also associated with early treatment response and the risk of ALL relapse. Our results provide insights into interactions between host and tumor genomes and their importance in ALL pathogenesis and prognosis. PMID:24141364

  8. The Impact of Prospective Telemedicine Implementation in the Management of Childhood Acute Lymphoblastic Leukemia in Recife, Brazil.

    Science.gov (United States)

    Pedrosa, Francisco; Shaikh, Faisal; Rivera, Gaston; Ribeiro, Raul; Qaddoumi, Ibrahim

    2017-10-01

    A gap in childhood cancer outcomes remains between developed and developing countries. Persistence of this gap may be caused by financial, social, or educational disparities. Twinning and distance learning initiatives may improve such disparities. Integrating telemedicine into pediatric oncology twinning programs enhances education and facilitates patient-centered capacity building. We performed an analysis of Web-based meetings held from August 2005 through July 2009 between the International Outreach Program at St. Jude Children's Research Hospital and the Instituto Materno Infantil de Pernambuco (IMIP) in Recife, Brazil. We determined the effect of these online conferences on the development and implementation of an innovative protocol for children with acute lymphoblastic leukemia (ALL) at IMIP. Meetings occurred in 45 months of the 48-month study period with an average of two meetings per month. A total of 163 new patients were discussed during the study period; we retrieved documentation of patient-related discussions for 147 of them, constituting 286 discussions. On average, each patient was discussed 1.9 times (range, 1-15 discussions/patient). Compared with that of the era predating the online meetings (1993-2005), overall mortality, early death, and relapse of patients with ALL decreased after the telemedicine program was instituted at IMIP. Personal dedication and institutional support are essential for successful telemedicine initiatives. Documentation and archival of meetings are important for accurately measuring outcomes and developing methods for improved care. Integration of telemedicine into twinning programs facilitates communication about interventions, leading to improved outcomes of pediatric patients with cancer.

  9. An adult patient who developed malignant fibrous histiocytoma 9 years after radiation therapy for childhood acute lymphoblastic leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Kato, Yasuhiro [National Hiroshima Hospital, Higashi-Hiroshima (Japan); Ohno, Norioki; Horikawa, Yoko; Nishimura, Shin-ichiro; Ueda, Kazuhiro; Shimose, Shoji [Hiroshima Univ. (Japan). School of Medicine

    2002-12-01

    A 24-year-old Japanese man with a history of acute lymphoblastic leukemia, which occurred during childhood, developed malignant fibrous histiocytoma of his left knee. His past history revealed that he had undergone leukemic blast cell invasion of the left knee and subsequent radiation therapy 9 years ago. The total radiation doses for the upper part of the left tibia and the lower part of the left femur were 60 Gy and 40 Gy, respectively. Neither distant metastasis nor a relapse of leukemia occurred. A curative resection of the left femur with a noninvasive margin was performed. Adjuvant chemotherapy including high-dose methotrexate was given successfully before and after surgery; this was followed by relapse-free survival for 3 years. The nature of postirradiation malignant fibrous histiocytoma is highly aggressive. When a patient complains of persistent symptoms in a previously irradiated field, the possibility of this tumor must be taken into account. The importance of early diagnosis cannot be over-emphasized. (author)

  10. Neurocognitive outcome in survivors of childhood acute lymphoblastic leukemia: experience at a tertiary care hospital in Korea.

    Science.gov (United States)

    Kim, Seong Joon; Park, Min Hyun; Lee, Jae Wook; Chung, Nak Gyun; Cho, Bin; Lee, In Goo; Chung, Seung Yun

    2015-04-01

    This study was conducted to investigate long-term neurocognitive outcomes and to determine associated risk factors in a cohort of Korean survivors of childhood acute lymphoblastic leukemia (ALL). Forty-two survivors of ALL were compared with 42 healthy controls on measures of a neurocognitive test battery. We analysed potential risk factors (cranial irradiation, sex, age at diagnosis, elapsed time from diagnosis, and ALL risk group) on neurocognitive outcomes. ALL patients had lower, but non-significant full-scale intelligence quotient (FSIQ, 107.2±12.2 vs. 111.7±10.2), verbal intelligence quotient (VIQ, 107.7±13.6 vs. 112.2±11.4), and performance intelligence quotient (PIQ, 106.3±14.2 vs. 110.1±10.7) scores than healthy controls. However, patients treated with cranial irradiation performed significantly lower on FSIQ (102.2±8.1), VIQ (103.3±11.7), and PIQ (101.4±13.2) compared to non-irradiated patients and healthy controls. ALL patients also had poor attention, concentration, and executive functions. Among ALL survivors, cranial irradiation was a risk factor for poor FSIQ, being male was a risk factor for poor PIQ, and younger age was a risk factor for poor attention. Therefore, the delayed cognitive effects of ALL treatment and its impact on quality of life require continuing monitoring and management.

  11. Dexamethasone exposure and memory function in adult survivors of childhood acute lymphoblastic leukemia: A report from the SJLIFE cohort.

    Science.gov (United States)

    Edelmann, Michelle N; Ogg, Robert J; Scoggins, Matthew A; Brinkman, Tara M; Sabin, Noah D; Pui, Ching-Hon; Srivastava, Deo Kumar; Robison, Leslie L; Hudson, Melissa M; Krull, Kevin R

    2013-11-01

    Dexamethasone is used in acute lymphoblastic leukemia (ALL) treatment, though long-term impact on central nervous system (CNS) function is unclear. As glucocorticoids influence hippocampal function, we investigated memory networks in survivors of childhood ALL treated with dexamethasone or prednisone. Neurocognitive assessment and functional magnetic resonance imaging (fMRI) were conducted in 38 adult survivors randomly recruited from cohorts treated on one of two standard treatment protocols, which differed primarily in the glucocorticoid administered during continuation therapy (dexamethasone [n = 18] vs. prednisone [n = 20]). Groups did not differ in age at diagnosis, age at evaluation, or cumulative intravenous or intrathecal methotrexate exposure. Survivors treated with dexamethasone demonstrated lower performance on multiple memory-dependent measures, including story memory (P = 0.01) and word recognition (P = 0.04), compared to survivors treated with only prednisone. Dexamethasone treatment was associated with decreased fMRI activity in the left retrosplenial brain region (effect size = 1.3), though the small sample size limited statistical significance (P = 0.08). Story memory was associated with altered activation in left inferior frontal-temporal brain regions (P = 0.007). Results from this pilot study suggest that adult survivors of ALL treated with dexamethasone are at increased risk for memory deficits and altered neural activity in specific brain regions and networks associated with memory function. Copyright © 2013 Wiley Periodicals, Inc.

  12. Germline genetic variations in methotrexate candidate genes are associated with pharmacokinetics, toxicity, and outcome in childhood acute lymphoblastic leukemia.

    Science.gov (United States)

    Radtke, Susanne; Zolk, Oliver; Renner, Bertold; Paulides, Marios; Zimmermann, Martin; Möricke, Anja; Stanulla, Martin; Schrappe, Martin; Langer, Thorsten

    2013-06-27

    The pharmacogenetics of methotrexate (MTX) was investigated in a large cohort of pediatric patients with acute lymphoblastic leukemia (ALL). Four hundred ninety-nine children with ALL from the ALL-BFM (Berlin-Frankfurt-Münster) 2000 trial who received 1996 courses of MTX at 5 g/m(2) were genotyped for 8 single nucleotide polymorphisms in 5 candidate genes of the MTX/folate pathway. Patients' MTX pharmacokinetics, MTX toxicities, and outcomes were correlated with the genotypes. The interindividual variability in MTX kinetics had a substantial genetic component between 68% and 75%. The SLCO1B1 rs4149056 variant was significantly associated with MTX kinetics. In a multiple regression model, MTX area under the concentration time curve (AUC)0-48h increased by 26% (P rs4149056 C allele. MTX AUC0-48h was a significant predictor of overall toxic adverse events during MTX courses (R(2) = 0.043; P < .001), whereas the thymidylate synthase rs34743033 tandem repeat polymorphism was predictive of stomatitis (R(2) = 0.018; P = .009), a frequent side effect of high-dose MTX. Multiple Cox regression analyses revealed an association of minimal residual disease (hazard ratio 7.3; P < .001) and methylenetetrahydrofolate reductase rs1801131 (hazard ratio 3.1; P = .015) with event-free survival in the ALL-BFM 2000 study population. Genetic variations substantially influence the kinetics and response to high-dose MTX therapy in childhood ALL.

  13. Post-induction residual leukemia in childhood acute lymphoblastic leukemia quantified by PCR correlates with in vitro prednisolone resistance

    DEFF Research Database (Denmark)

    Schmiegelow, K; Nyvold, C; Seyfarth, J

    2001-01-01

    Most prognostic factors in childhood acute lymphoblastic leukemia (ALL) are informative for groups of patients, whereas new approaches are needed to predict the efficacy of chemotherapy for the individual patient. The residual leukemia following 4 weeks of induction therapy with prednisolone......, vincristine, doxorubicin and i.t. methotrexate and the in vitro resistance to prednisolone, vincristine, and doxorubicin were measured in 30 boys and 12 girls with B (n = 34) or T lineage (n = 8) ALL. The residual leukemia was quantified after 2 (MRD-D15, n = 29) and 4 weeks (MRD-PI, n = 42) of induction.......05-668). Both MRD-D15 and MRD-PI correlated significantly with the in vitro resistance to prednisolone (MRD-D15: rs = 0.41, P = 0.03; MRD-PI: rs = 0.39, P = 0.01); but not to in vitro vincristine or doxorubicin resistance. The correlations between MRD and in vitro prednisolone resistance were even more...

  14. Unusual maxillary osteoblastic and osteolytic lesions presenting as an initial manifestation of childhood acute myeloid leukemia: A case report.

    Science.gov (United States)

    Shimizu, Rikuka; Ohga, Noritaka; Miyakoshi, Masaaki; Asaka, Takuya; Sato, Jun; Kitagawa, Yoshimasa

    2017-01-01

    Changes in facial bones may represent a manifestation of systemic disease. Dentists play an important role in the early detection of these manifestations of complex systemic diseases. A case of unusual maxillary mixed (osteoblastic and osteolytic) lesions as an initial manifestation of childhood acute myeloid leukemia (AML) is presented. A 12-year-old male patient was referred to the Department of Oral Medicine complaining of severe swelling in the right buccal region. 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) showed enhanced FDG uptake in the right maxillary sinus. In addition, PET maximum intensity projection image showed diffused FDG uptake in the entire bone marrow. Bone marrow aspiration was performed on the lumbar vertebra, and fluorescence in situ hybridization (FISH) demonstrated AML. The patient was diagnosed with AML (M5a) and treated with chemotherapy by the pediatric department. Six months later, the patient achieved complete remission. After chemotherapy, the disappearance of the osteoblastic and osteolytic lesion and 18F-FDG accumulation were confirmed by PET/CT. Dentists should be familiar with oral manifestations of leukemia because early detection of oral lesions would increase the life span of the patients and reduce the severity of complications.

  15. Leukoencephalopathy and long-term neurobehavioural, neurocognitive, and brain imaging outcomes in survivors of childhood acute lymphoblastic leukaemia treated with chemotherapy: a longitudinal analysis.

    Science.gov (United States)

    Cheung, Yin Ting; Sabin, Noah D; Reddick, Wilburn E; Bhojwani, Deepa; Liu, Wei; Brinkman, Tara M; Glass, John O; Hwang, Scott N; Srivastava, Deokumar; Pui, Ching-Hon; Robison, Leslie L; Hudson, Melissa M; Krull, Kevin R

    2016-10-01

    Leukoencephalopathy is observed in some children undergoing chemotherapy for acute lymphoblastic leukaemia, although its effects on long-term outcomes is unknown. This study examines the associations between acute leukoencephalopathy and neurobehavioural, neurocognitive, and brain white matter imaging outcomes in long-term survivors of childhood acute lymphoblastic leukaemia treated with chemotherapy without cranial radiation. In this longitudinal analysis, we used data of children with acute lymphoblastic leukaemia at St Jude Children's Research Hospital (Memphis, TN, USA) who had been treated between June 1, 2000, and Oct 31, 2010. Eligible patients were diagnosed with non-B-cell acute lymphoblastic leukaemia, aged at least 8 years, and survivors with at least 5 years since their initial diagnosis. Brain MRIs obtained during active therapy were systematically coded for leukoencephalopathy using Common Terminology Criteria for Adverse Event version 4. At least 5 years after their diagnosis, survivors completed neurocognitive testing, another brain MRI, and their parents completed neurobehavioural ratings of their child (Behavior Rating Inventory of Executive Function [BRIEF]). Follow-up MRI included diffusion tensor imaging to assess white matter integrity, with indices of fractional anisotropy, axial diffusivity, and radial diffusivity from frontal lobes, parietal lobes, and in the frontostriatal tract. The neuroradiologist, who assessed abnormal MRIs, was masked to both group assignment of survivors and the neurobehavioural and neurocognitive outcomes. The primary outcomes were neurobehavioural function, assessed from completed BRIEF, and neurocognitive performance, measured by direct neurocognitive tests (Delis-Kaplan Executive Function System, Wechsler Intelligence Scale for Children-IV/Wechsler Adult Intelligence Scale-III, Rey-Osterrieth Complex Figure Test, and Lafayette Grooved Pegboard Test). This study had completed enrolment in October, 2014, and is

  16. Acute Motor Axonal Neuropathy (Aman) With Motor Conduction Blocks In Childhood; Case Report.

    Science.gov (United States)

    Yildirim, Serhan; Adviye, Rahşan; Gül, Hakan Levent; Türk Börü, Ülkü

    2016-01-01

    Objective Acute motor axonal neuropathy (AMAN), characterized with decreased compound muscle action potentials (CMAP) and absence of demyelinating findings in electrophysiological studies, is a subtype of Guillain-Barre Syndrome (GBS). A 4 yr-old male patient presented with ascending weakness, dysarthria and dysphagia to İstanbul Dr. Lütfi Kırdar Kartal Training and Research Hospital Neurology outpatient for three days to in 2012. Dysphonia, restricted eye movements, flaccid tetraplegia and areflexia were found in neurological examination. There were motor conduction blocks in all peripheral nerves in electrophysiological studies.According to these findings the patient was diagnosed as Acute Inflammatory Demyelinating Polyradiculoneuropathy (AIDP). Reduction of CMAP amplitudes in posterior tibial nerve, absence of CMAPs in median, ulnar and peroneal nerves and loss of motor conduction blocks were found in following electrophysiological studies. According to these findings, patient was diagnosed as AMAN. Motor conduction blocks may appear in early stage of AMAN and they disappear in later examinations. That's why electrophysiological studies must be repeated in patients with GBS.

  17. Identification of de Novo Fanconi Anemia in Younger Patients With Newly Diagnosed Acute Myeloid Leukemia

    Science.gov (United States)

    2016-05-13

    Childhood Acute Erythroleukemia (M6); Childhood Acute Megakaryocytic Leukemia (M7); Childhood Acute Minimally Differentiated Myeloid Leukemia (M0); Childhood Acute Monoblastic Leukemia (M5a); Childhood Acute Monocytic Leukemia (M5b); Childhood Acute Myeloblastic Leukemia With Maturation (M2); Childhood Acute Myeloblastic Leukemia Without Maturation (M1); Childhood Acute Myelomonocytic Leukemia (M4); Childhood Myelodysplastic Syndromes; Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndromes; Fanconi Anemia; Refractory Anemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Refractory Anemia With Ringed Sideroblasts; Secondary Myelodysplastic Syndromes; Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

  18. Neurocognitive outcome and white matter anisotropy in childhood acute lymphoblastic leukemia survivors treated with different protocols.

    Science.gov (United States)

    ElAlfy, Mohsen; Ragab, Iman; Azab, Inas; Amin, Shaimaa; Abdel-Maguid, Marwa

    2014-03-01

    Neurocognitive outcome affects the quality of life of ALL survivors. This study is aimed to assess the prevalence of neurocognitive dysfunction by psychometric and imaging tools in survivors of childhood ALL, treated with 3 different protocols and the effect of time elapsed since the end of chemotherapy. Sixty-two ALL survivors aged 6-18 years and treated in the period 1997-2007 and 60 healthy age and sex matched controls were subjected to neurocognitive testing using Wechsler Intelligence Scale for Children, Benton visual retention (BVRT) and Trail Making test (TMT), followed by diffusion weighed and diffusion tensor MRI for calculation of fraction anisotropy (FA). Survivors underwent revision of protocol and type of CNS therapy. Three different protocols were used: modified BFM 83, BFM 90, and CCG. Survivors treated with modified CCG protocol showed a significant decrease in all cognitive tests compared to control (ptests between BFM 83 and control group. Frontal FA was lower in CCG treated group compared to control, BFM 90 and BFM 83 groups (pchildhood ALL survivors.

  19. Childhood Sexual Abuse and Acute Alcohol Effects on Men's Sexual Aggression Intentions.

    Science.gov (United States)

    Davis, Kelly Cue; Schraufnagel, Trevor J; Jacques-Tiura, Angela J; Norris, Jeanette; George, William H; Kiekel, Preston A

    2012-04-01

    OBJECTIVE: Although research has established childhood sexual abuse (CSA) as a risk factor for men's perpetration of sexual aggression, there has been little investigation of the factors undergirding this association. This study represents one of the first to use a laboratory-based sexual aggression analogue coupled with an alcohol administration protocol to investigate the pathways through which CSA and alcohol influence men's self-reported sexual aggression intentions. METHOD: After completing background questionnaires, male social drinkers (N = 220) were randomly assigned to a control, placebo, low alcohol dose or high alcohol dose condition. Following beverage consumption, participants read a sexual scenario in which the female partner refused to have unprotected sexual intercourse, after which they completed dependent measures. RESULTS: Path analysis indicated that men with a CSA history and intoxicated men perceived the female character as more sexually aroused and reported stronger sexual entitlement cognitions, both of which were in turn associated with greater condom use resistance and higher sexual aggression intentions. Exploratory analyses revealed that intoxication moderated the effects of CSA history on sexual entitlement cognitions, such that sexual entitlement cognitions were highest for men who had a CSA history and consumed alcohol. CONCLUSIONS: Findings suggest that CSA history may facilitate sexual assault perpetration through its effects on in-the-moment cognitions, and that these effects may be exacerbated by alcohol intoxication.

  20. [Treatment of childhood acute lymphoblastic leukemia in a community hospital of the state of Veracruz].

    Science.gov (United States)

    Verduzco-Rodríguez, L; Ibarra-Colado, J

    1998-01-01

    To describe the results of treatment of 36 consecutive children with acute lymphoblastic leukemia attending a second level community hospital in the Mexican State of Veracruz. They were from families with very poor resources seen free of charge. Most (75%) were high risk cases. The most common high risk factors were an age outside the range of 2 to 9 years (53%), a WBC count above 50 thousand/microL (36%) and an L-2 lymphocyte morphology (39%). Disease-free survival was 64% at 36 months whereas event-free survival was 47% at 36 months which are low in comparison with the data in the literature. We believe we were able to obtain good results in the treatment of our leukemic cases which was not only a mostly high risk group but also had to contend with poor nutritional, cultural and socioeconomic conditions and with disease-related factors present in their communities.

  1. Acute Disseminated Encephalomyelitis: A Review of Eleven Cases in Childhood in North of Iran

    Directory of Open Access Journals (Sweden)

    Ali Nikkhah

    2016-01-01

    Full Text Available Background: Acute disseminated encephalomyelitis (ADEM is an inflammatory demyelinating disorder. The pathogenesis is unclear, but it is thought to be immune-mediated. The prognosis is favorable, with most children making a full recovery. Objectives: The present report analyzed different clinical presentations, response to treatment and outcome in a series of 11 patients with ADEM who referred to our tertiary center in north of Iran from 2010 to 2014. Materials and Methods: In this retrospective simple descriptive review, eleven cases with ADEM admitted in the neurology ward from 2010 to 2014 were enrolled. The clinical findings and laboratory and imaging results of patients were reviewed. All of these cases were evaluated with neurological examination, serologic tests for bacterial meningitis and viral encephalitis (especially, herpes simplex virus and brain MRI without contrast. After discharge, patients were followed for at least six months (6 to 12 months clinically and radiologically. Results: Of 11 children, 8 were male and 3 female. Their ages ranged between 4 and 10 years. The mean interval between the preceding infection and symptoms of encephalomyelitis was nine days. The most common presenting symptoms were ataxia in 45.4%, fever and headache in 36.4% and altered consciousness in 18.2% of patients. Neurological examination revealed pyramidal motor signs such as brisk deep tendon reflexes (hyperreflexia (81.8%, cranial nerve involvement (18.2%, dysarthria (9.1% and abnormal movements (9.1%. We followed up these patients in long-term for 6 to 12 months. Only in 1 child who received IVIG, mild ataxia had reminded. Conclusions: The prognosis of acute disseminated encephalomyelitis (ADEM is favorable. Early diagnosis and prompt treatment of ADEM would probably reduce morbidity.

  2. Rotavirus genotypes associated with childhood severe acute diarrhoea in southern Ghana: a cross-sectional study.

    Science.gov (United States)

    Enweronu-Laryea, Christabel C; Sagoe, Kwamena W; Damanka, Susan; Lartey, Belinda; Armah, George E

    2013-09-14

    Rotavirus immunization has been effective in developed countries where genotype G1P[8] is the predominant rotavirus strain. Knowledge of circulating strains in a population before introduction of rotavirus immunization program will be useful in evaluating the effect of the intervention. Rotavirus was identified by enzyme immuno-assay (EIA) on stool specimens of children (age 0-59 months) hospitalized with acute gastroenteritis from August 2007 to February 2011 in Accra, Ghana. Rotavirus positive specimens were further characterized by polyacrylamide gel electrophoresis (PAGE) and reverse-transcriptase polymerase chain reaction (RT-PCR). Of the 2277 acute gastroenteritis hospitalizations 1099 (48.2%) were rotavirus-positive by EIA. Of the 1099 cases 977 (89%) were PAGE positive. All EIA positive specimens were further subjected to RT-PCR and 876 (79.7%) had sufficient material for characterization. Of these 876 cases, 741 (84.6%) were assigned G genotype, 709 (80.9%) P genotype, and 624 (71.2%) both G and P genotypes. We identified 8 G genotypes (G1, G2, G3, G4, G8, G9, G10, G12) and 3 P genotypes (P[4], P[6], P[8]). G1 (50.9%), G2 (18.8%), G3 (12.8%), P[8] (36.1%) and P[6] (30.7%) were the most prevalent. The most prevalent genotype combination was G1P[8] (28%). Mixed G (7.3%) and P (24.2%) genotypes were not uncommon. There was year-by-year and seasonal variations for most genotypes. There is great diversity of rotavirus strains in children with severe gastroenteritis in southern Ghana. Even though cross-protection with vaccine-induced immunity occurs, continued strain surveillance is recommended after the introduction of rotavirus vaccine in the national immunization program.

  3. Streptococcal necrotising myositis of obturator internus and piriformis in a type 2 diabetic patient presenting as sepsis of unknown origin.

    Science.gov (United States)

    Sharma, P R; McEvoy, H C; Floyd, D C

    2011-09-01

    This report describes a case of necrotising myositis of the obturator internus and piriformis muscles. Necrotising myositis is a rare result of group A streptococcal infection. It is usually fatal and has not been described previously in the obturator internus and piriformis. We describe how, following presentation to an emergency department, rapid diagnosis was arrived at by clinically guided radiological investigation. The report considers the possible aetiology of the condition, the diagnosis and its management, and reviews the relevant literature.

  4. Risk of hospitalization among survivors of childhood and adolescent acute lymphoblastic leukemia compared to siblings and a general population sample.

    Science.gov (United States)

    Ou, Judy Y; Smits-Seemann, Rochelle R; Kaul, Sapna; Fluchel, Mark N; Sweeney, Carol; Kirchhoff, Anne C

    2017-08-01

    Acute Lymphoblastic Leukemia (ALL) has a high survival rate, but cancer-related late effects in the early post-treatment years need documentation. Hospitalizations are an indicator of the burden of late effects. We identify rates and risk factors for hospitalization from five to ten years after diagnosis for childhood and adolescent ALL survivors compared to siblings and a matched population sample. 176 ALL survivors were diagnosed at ≤22 years between 1998 and 2008 and treated at an Intermountain Healthcare facility. The Utah Population Database identified siblings, an age- and sex-matched sample of the Utah population, and statewide inpatient hospital discharges. Sex- and birth year-adjusted Poisson models with Generalized Estimating Equations and robust standard errors calculated rates and rate ratios. Cox proportional hazards models identified demographic and clinical risk factors for hospitalizations among survivors. Hospitalization rates for survivors (Rate:3.76, 95% CI=2.22-6.36) were higher than siblings (Rate:2.69, 95% CI=1.01-7.18) and the population sample (Rate:1.87, 95% CI=1.13-3.09). Compared to siblings and population comparisons, rate ratios (RR) were significantly higher for survivors diagnosed between age 6 and 22 years (RR:2.87, 95% CI=1.03-7.97 vs siblings; RR:2.66, 95% CI=1.17-6.04 vs population comparisons). Rate ratios for diagnosis between 2004 and 2008 were significantly higher compared to the population sample (RR:4.29, 95% CI=1.49, 12.32), but not siblings (RR:2.73, 95% CI=0.54, 13.68). Survivors originally diagnosed with high-risk ALL did not have a significantly higher risk than siblings or population comparators. However, high-risk ALL survivors (Hazard ratio [HR]:3.36, 95% CI=1.33-8.45) and survivors diagnosed from 2004 to 2008 (HR:9.48, 95% CI=1.93-46.59) had the highest risk compared to their survivor counterparts. Five to ten years after diagnosis is a sensitive time period for hospitalizations in the ALL population. Survivors of

  5. Feasibility and initial effectiveness of home exercise during maintenance therapy for childhood acute lymphoblastic leukemia.

    Science.gov (United States)

    Esbenshade, Adam J; Friedman, Debra L; Smith, Webb A; Jeha, Sima; Pui, Ching-Hon; Robison, Leslie L; Ness, Kirsten K

    2014-01-01

    Children with acute lymphoblastic leukemia (ALL) are at increased risk of obesity and deconditioning from cancer therapy. This pilot study assessed feasibility/initial efficacy of an exercise intervention for patients with ALL undergoing maintenance therapy. Participants were aged 5 to 10 years, receiving maintenance therapy, in first remission. A 6-month home-based intervention, with written and video instruction, was supervised with weekly calls from an exercise coach. Pre- and poststudy testing addressed strength, flexibility, fitness, and motor function. Seventeen patients enrolled (participation 63%). Twelve (71%) finished the intervention, completing 81.7 ± 7.2% of prescribed sessions. Improvements of 5% or more occurred in 67% for knee and 75% for grip strength, 58% for hamstring/low-back and 83% for ankle flexibility, 75% for the 6-Minute Walk Test, and 33% for performance on the Bruininks-Oseretsky Test of Motor Proficiency Version 2. This pilot study demonstrated that exercise intervention during ALL therapy is feasible and has promise for efficacy.

  6. Genomic and transcriptional landscape of P2RY8-CRLF2-positive childhood acute lymphoblastic leukemia

    Science.gov (United States)

    Vesely, C; Frech, C; Eckert, C; Cario, G; Mecklenbräuker, A; zur Stadt, U; Nebral, K; Kraler, F; Fischer, S; Attarbaschi, A; Schuster, M; Bock, C; Cavé, H; von Stackelberg, A; Schrappe, M; Horstmann, M A; Mann, G; Haas, O A; Panzer-Grümayer, R

    2017-01-01

    Children with P2RY8-CRLF2-positive acute lymphoblastic leukemia have an increased relapse risk. Their mutational and transcriptional landscape, as well as the respective patterns at relapse remain largely elusive. We, therefore, performed an integrated analysis of whole-exome and RNA sequencing in 41 major clone fusion-positive cases including 19 matched diagnosis/relapse pairs. We detected a variety of frequently subclonal and highly instable JAK/STAT but also RTK/Ras pathway-activating mutations in 76% of cases at diagnosis and virtually all relapses. Unlike P2RY8-CRLF2 that was lost in 32% of relapses, all other genomic alterations affecting lymphoid development (58%) and cell cycle (39%) remained stable. Only IKZF1 alterations predominated in relapsing cases (P=0.001) and increased from initially 36 to 58% in matched cases. IKZF1’s critical role is further corroborated by its specific transcriptional signature comprising stem cell features with signs of impaired lymphoid differentiation, enhanced focal adhesion, activated hypoxia pathway, deregulated cell cycle and increased drug resistance. Our findings support the notion that P2RY8-CRLF2 is dispensable for relapse development and instead highlight the prominent rank of IKZF1 for relapse development by mediating self-renewal and homing to the bone marrow niche. Consequently, reverting aberrant IKAROS signaling or its disparate programs emerges as an attractive potential treatment option in these leukemias. PMID:27899802

  7. JAK2 aberrations in childhood B-cell precursor acute lymphoblastic leukemia

    Science.gov (United States)

    de Goffau-Nobel, Willemieke; Hoogkamer, Alex Q.; Boer, Judith M.; Boeree, Aurélie; van de Ven, Cesca; Koudijs, Marco J.; Besselink, Nicolle J.M.; de Groot-Kruseman, Hester A.; Zwaan, Christian Michel; Horstmann, Martin A.; Pieters, Rob; den Boer, Monique L.

    2017-01-01

    JAK2 abnormalities may serve as target for precision medicines in pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL). In the current study we performed a screening for JAK2 mutations and translocations, analyzed the clinical outcome and studied the efficacy of two JAK inhibitors in primary BCP-ALL cells. Importantly, we identify a number of limitations of JAK inhibitor therapy. JAK2 mutations mainly occurred in the poor prognostic subtypes BCR-ABL1-like and non- BCR-ABL1-like B-other (negative for sentinel cytogenetic lesions). JAK2 translocations were restricted to BCR-ABL1-like cases. Momelotinib and ruxolitinib were cytotoxic in both JAK2 translocated and JAK2 mutated cells, although efficacy in JAK2 mutated cells highly depended on cytokine receptor activation by TSLP. However, our data also suggest that the effect of JAK inhibition may be compromised by mutations in alternative survival pathways and microenvironment-induced resistance. Furthermore, inhibitors induced accumulation of phosphorylated JAK2Y1007, which resulted in a profound re-activation of JAK2 signaling upon release of the inhibitors. This preclinical evidence implies that further optimization and evaluation of JAK inhibitor treatment is necessary prior to its clinical integration in pediatric BCP-ALL. PMID:29163799

  8. Idiotype as a tumor-specific marker in childhood B cell acute lymphoblastic leukemia.

    Science.gov (United States)

    Carroll, W L; Link, M P; Cleary, M L; Bologna, S; Carswell, C; Amylon, M D; Smith, S D; Levy, R

    1988-04-01

    Immunoglobulin (Ig) or idiotype (Id) is a tumor-specific target in those B cell malignancies that express this molecule on their surface. We explored the biology of B cell acute lymphoblastic leukemia (B cell ALL) using Id as a tumor marker. In this report we describe the development of anti-Id monoclonal antibodies (MAB) for two children with B cell ALL. These reagents were used retrospectively to study tumor kinetics and to detect residual disease after chemotherapy. In both cases serum Id values were strikingly high at diagnosis (1.2 mg/mL and 10.8 mg/mL), suggesting that the tumor cells were relatively mature B cells capable of significant antibody production. In both patients the serum Id levels fell with the institution of therapy and confirmed that the patients were in remission. Increasing serum Id predicted relapse four months before conventional methods in patient 1, and Id proved to be a more sensitive measure of tumor burden than Southern blot analysis of rearranged Ig genes in bone marrow samples. Surprisingly, low levels of Id were redetected in the second patient just before completing therapy and have persisted for over a year despite the absence of clinical evidence of recurrent disease. Thus, serum Id levels reflect tumor burden during initial therapy but may not necessarily predict tumor progression after a complete clinical remission.

  9. Oxidative DNA base damage and antioxidant enzyme levels in childhood acute lymphoblastic leukemia.

    Science.gov (United States)

    Sentürker, S; Karahalil, B; Inal, M; Yilmaz, H; Müslümanoglu, H; Gedikoglu, G; Dizdaroglu, M

    1997-10-27

    We have investigated the levels of several antioxidant enzymes and the level of oxidative DNA base damage in lymphocytes of children with acute lymphoblastic leukemia (ALL) and in disease-free children. Children with ALL had just been diagnosed with the disease and had received no therapy prior to obtaining blood samples. A multitude of typical hydroxyl radical-induced base lesions in lymphocyte DNA of children were identified and quantified by gas chromatography-isotope dilution mass spectrometry. Higher levels of DNA base lesions were observed in patients with ALL than in children without the disease. The levels of the antioxidant enzymes glutathione peroxidase, catalase and superoxide dismutase in lymphocytes of ALL patients were lower than in lymphocytes of controls. These findings are in agreement with earlier observations in various types of adulthood cancer. Some of the identified DNA base lesions are known to possess premutagenic properties and may play a role in carcinogenesis. The results may indicate a possible link between decreased activities of antioxidant enzymes and increased levels of DNA base lesions due to oxidative damage, and support the notion that free radical reactions may be increased in malignant cells.

  10. Increased μ-Calpain Activity in Blasts of Common B-Precursor Childhood Acute Lymphoblastic Leukemia Correlates with Their Lower Susceptibility to Apoptosis.

    Directory of Open Access Journals (Sweden)

    Anna Mikosik

    Full Text Available Childhood acute lymphoblastic leukemia (ALL blasts are characterized by inhibited apoptosis promoting fast disease progress. It is known that in chronic lymphocytic and acute myeloid leukemias the reduced apoptosis is strongly related with the activity of calpain-calpastatin system (CCS composed of cytoplasmic proteases--calpains--performing the modulatory proteolysis of key proteins involved in cell proliferation and apoptosis, and of their endogenous inhibitor--calpastatin. Here, the CCS protein abundance and activity was for the first time studied in childhood ALL blasts and in control bone marrow CD19+ B cells by semi-quantitative flow cytometry and western blotting of calpastatin fragments resulting from endogenous calpain activity. Significantly higher μ-calpain (CAPN1 gene transcription, protein amounts and activity (but not those of m-calpain, with calpastatin amount and transcription of its gene (CAST greatly varying were observed in CD19(+ ALL blasts compared to control cells. Significant inverse relation between the amount/activity of calpain and spontaneous apoptosis was noted. Patients older than 10 years (considered at higher risk displayed increased amounts and activities of blast calpain. Finally, treatment of blasts with the tripeptide calpain inhibitors II and IV significantly and in dose-dependent fashion increased the percentage of blasts entering apoptosis. Together, these findings make the CCS a potential new predictive tool and therapeutic target in childhood ALL.

  11. Screening survivors of childhood acute lymphoblastic leukemia for obesity, metabolic syndrome, and insulin resistance.

    Science.gov (United States)

    Karakurt, Hasan; Sarper, Nazan; Kılıç, Suar Çakı; Gelen, Sema Aylan; Zengin, Emine

    2012-09-01

    Acute lymphoblastic leukemia (ALL) survivors were screened for risk factors of cardiovascular disease. Forty-four ALL survivors in first remission were enrolled. Twenty-six also received 12-18 Gy cranial radiotherapy (RT). Patients' body mass indexes (BMIs) at dignosis and during the study were compared. Metabolic syndrome (MS) evaluation was performed in patients, parents, and siblings older than 6 years. Homeostasis Model Assessment (HOMA) index of the survivors was also calculated. In survivors with impaired fasting glucose levels, oral glucose tolerance test (OGTT) was performed. Thyroid functions and IGF-1 and/or IGFBP-3 levels of the survivors who received cranial RT were evaluated. Median age of the survivors was 11.5 years (6-23). At diagnosis, mean BMI percentile was 46.7 (3-95) and mean z-score was -0.09 ± 1.14; during the study, these values rose to 71.1 ± 25.6 (3-100) and 0.8 ± 0.94, respectively (P obese at diagnosis and during the study, respectively (P = .005). Survivors had significantly higher BMI percentile and BMI z-score compared to their siblings (P = .006 and P = .011, respectively). The study group was small and we could not show a correlation of the patients' obesity with RT, thyroid functions, IGF-1, and IGFBP-3 levels. In three survivors (6.8%), there was MS. Maternal and paternal MS was not found as a risk factor for MS of the survivors (P = .1, P = .5, respectively). The HOMA index revealed insulin resistance (IR) in 12 (27.2%) of the survivors, whereas OGTT revealed abnormal glucose regulation and/or IR in four. As a conclusion, ALL survivors have high risk for obesity and MS.

  12. Mercaptopurine/Methotrexate Maintenance Therapy of Childhood Acute Lymphoblastic Leukemia: Clinical Facts and Fiction

    Science.gov (United States)

    Nielsen, Stine N.; Frandsen, Thomas L.; Nersting, Jacob

    2014-01-01

    The antileukemic mechanisms of 6-mercaptopurine (6MP) and methotrexate (MTX) maintenance therapy are poorly understood, but the benefits of several years of myelosuppressive maintenance therapy for acute lymphoblastic leukemia are well proven. Currently, there is no international consensus on drug dosing. Because of significant interindividual and intraindividual variations in drug disposition and pharmacodynamics, vigorous dose adjustments are needed to obtain a target degree of myelosuppression. As the normal white blood cell counts vary by patients’ ages and ethnicity, and also within age groups, identical white blood cell levels for 2 patients may not reflect the same treatment intensity. Measurements of intracellular levels of cytotoxic metabolites of 6MP and MTX can identify nonadherent patients, but therapeutic target levels remains to be established. A rise in serum aminotransferase levels during maintenance therapy is common and often related to high levels of methylated 6MP metabolites. However, except for episodes of hypoglycemia, serious liver dysfunction is rare, the risk of permanent liver damage is low, and aminotransferase levels usually normalize within a few weeks after discontinuation of therapy. 6MP and MTX dose increments should lead to either leukopenia or a rise in aminotransferases, and if neither is experienced, poor treatment adherence should be considered. The many genetic polymorphisms that determine 6MP and MTX disposition, efficacy, and toxicity have precluded implementation of pharmacogenomics into treatment, the sole exception being dramatic 6MP dose reductions in patients who are homozygous deficient for thiopurine methyltransferase, the enzyme that methylates 6MP and several of its metabolites. In conclusion, maintenance therapy is as important as the more intensive and toxic earlier treatment phases, and often more challenging. Ongoing research address the applicability of drug metabolite measurements for dose adjustments

  13. The treatment of childhood acute lymphoblastic leukemia in Guatemala: Biologic features, treatment hurdles, and results.

    Science.gov (United States)

    Antillón, Federico G; Blanco, Jessica G; Valverde, Patricia D; Castellanos, Mauricio; Garrido, Claudia P; Girón, Veronica; Letona, Tomas R; Osorio, Emilia J; Borrayo, Dyna A; Mack, Ricardo A; Melgar, Mario A; Lorenzana, Rodolfo; Ribeiro, Raul C; Metzger, Monika; Conter, Valentino; Rossi, Emanuela; Valsecchi, Maria Grazia

    2017-02-01

    The National Pediatric Oncology Unit (UNOP) is the only pediatric hemato-oncology center in Guatemala. Patients ages 1 to 17 years with acute lymphoblastic leukemia (ALL) were treated according to modified ALL Intercontinental Berlin-Frankfurt-Münster (IC-BFM) 2002 protocol. Risk classification was based on age, white blood cell count, immunophenotype, genetics (when available), and early response to therapy. From July 2007 to June 2014, 787 patients were treated, including 160 who had standard-risk ALL, 450 who had intermediate-risk ALL, and 177 who had high-risk ALL. The induction death rate was 6.6%, and the remission rate was 92.9%. The rates of death and treatment abandonment during first complete remission were 4.8% and 2.5%, respectively. At a median observation time of 3.6 years, and with abandonment considered an event, the 5-year event-free survival and overall survival estimates ( ± standard error) were 56.2% ± 2.1% and 64.1% ± 2.1%, respectively, with a 5-year cumulative incidence of relapse of 28.9% ± 2.0%. Twenty-one of 281 patients (7.5%) investigated were positive for the ets variant 6/runt-related transcription factor 1 (ETV6/RUNX1) fusion. A well organized center in a low-middle-income country can overcome the disadvantages of malnutrition and reduce abandonment. Outcomes remain suboptimal because of late diagnosis, early death, and a high relapse rate, which may have a partly genetic basis. Earlier diagnosis, better management of complications, and better knowledge of ALL will improve outcomes. Cancer 2017;123:436-448. © 2016 American Cancer Society. © 2016 American Cancer Society.

  14. Spectrum of centrosome autoantibodies in childhood varicella and post-varicella acute cerebellar ataxia

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    Stinton Laura M

    2003-09-01

    Full Text Available Abstract Background Sera from children with post-varicella infections have autoantibodies that react with centrosomes in brain and tissue culture cells. We investigated the sera of children with infections and post-varicella ataxia and related conditions for reactivity to five recombinant centrosome proteins: γγ-enolase, pericentrin, ninein, PCM-1, and Mob1. Methods Sera from 12 patients with acute post-varicella ataxia, 1 with post-Epstein Barr virus (EBV ataxia, 5 with uncomplicated varicella infections, and other conditions were tested for reactivity to cryopreserved cerebellum tissue and recombinant centrosome proteins. The distribution of pericentrin in the cerebellum was studied by indirect immunofluorescence (IIF using rabbit antibodies to the recombinant protein. Antibodies to phospholipids (APL were detected by ELISA. Results Eleven of 12 children with post-varicella ataxia, 4/5 children with uncomplicated varicella infections, 1/1 with post-EBV ataxia, 2/2 with ADEM, 1/2 with neuroblastoma and ataxia, and 2/2 with cerebellitis had antibodies directed against 1 or more recombinant centrosome antigens. Antibodies to pericentrin were seen in 5/12 children with post-varicella ataxia but not in any of the other sera tested. IIF demonstrated that pericentrin is located in axons and centrosomes of cerebellar cells. APL were detected in 75% of the sera from children with post-varicella ataxia and 50% of children with varicella without ataxia and in none of the controls. Conclusion This is the first study to show the antigen specificity of anti-centrosome antibodies in children with varicella. Our data suggest that children with post-varicella ataxia have unique autoantibody reactivity to pericentrin.

  15. Recent advances in the diagnosis and management of childhood acute promyelocytic leukemia

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    Eun Sun Yoo

    2011-03-01

    Full Text Available Since the successful introduction of all-trans-retinoic acid (ATRA and its combination with anthracycline-containing chemotherapy, the prognosis for acute promyelocytic leukemia (APL has markedly improved. With ATRA and anthracycline-based-chemotherapy, the complete remission rate is greater than 90%, and the long-term survival rate is 70&#8210;89%. Moreover, arsenic trioxide (ATO, which was introduced for APL treatment in 1994, resulted in excellent remission rates in relapsed patients with APL, and more recently, several clinical studies have been designed to explore its role in initial therapy either alone or in combination with ATRA. APL is a rare disease in children and is frequently associated with hyperleukocytosis, which is a marker for higher risk of relapse and an increased incidence of microgranular morphology. The frequency of occurrence of the promyelocytic leukemia/ retinoic acid receptor-alpha (PML/RAR?#6752;isoforms bcr 2 and bcr 3 is higher in children than in adults. Although recent clinical studies have reported comparable long-term survival rates in patients with APL, therapy for APL in children is challenging because of the risk of early death and the potential long-term cardiac toxicity resulting from the need to use high doses of anthracyclines. Additional prospective, randomized, large clinical trials are needed to address several issues in pediatric APL and to possibly minimize or eliminate the need for chemotherapy by combining ATRA and ATO. In this review article, we discuss the molecular pathogenesis, diagnostic progress, and most recent therapeutic advances in the treatment of children with APL.

  16. Health-related quality of life in long-term survivors of relapsed childhood acute lymphoblastic leukemia.

    Directory of Open Access Journals (Sweden)

    Stefan Essig

    Full Text Available BACKGROUND: Relapses occur in about 20% of children with acute lymphoblastic leukemia (ALL. Approximately one-third of these children can be cured. Their risk for late effects is high because of intensified treatment, but their health-related quality of life (HRQOL was largely unmeasured. Our aim was to compare HRQOL of ALL survivors with the general population, and of relapsed with non-relapsed ALL survivors. METHODOLOGY/PRINCIPAL FINDINGS: As part of the Swiss Childhood Cancer Survivor Study (SCCSS we sent a questionnaire to all ALL survivors in Switzerland who had been diagnosed between 1976-2003 at age <16 years, survived ≥5 years, and were currently aged ≥16 years. HRQOL was assessed with the Short Form-36 (SF-36, which measures four aspects of physical health and four aspects of mental health. A score of 50 corresponded to the mean of a healthy reference population. We analyzed data from 457 ALL survivors (response: 79%. Sixty-one survivors had suffered a relapse. Compared to the general population, ALL survivors reported similar or higher HRQOL scores on all scales. Survivors with a relapse scored lower in general health perceptions (51.6 compared to those without (55.8;p=0.005, but after adjusting for self-reported late effects, this difference disappeared. CONCLUSION/SIGNIFICANCE: Compared to population norms, ALL survivors reported good HRQOL, even after a relapse. However, relapsed ALL survivors reported poorer general health than non-relapsed. Therefore, we encourage specialists to screen for poor general health in survivors after a relapse and, when appropriate, specifically seek and treat underlying late effects. This will help to improve patients' HRQOL.

  17. An Allele of IKZF1 (Ikaros) Conferring Susceptibility to Childhood Acute Lymphoblastic Leukemia Protects Against Type 1 Diabetes

    Science.gov (United States)

    Swafford, Austin D.-E.; Howson, Joanna M.M.; Davison, Lucy J.; Wallace, Chris; Smyth, Deborah J.; Schuilenburg, Helen; Maisuria-Armer, Meeta; Mistry, Trupti; Lenardo, Michael J.; Todd, John A.

    2011-01-01

    OBJECTIVE IKZF1 encoding Ikaros, an essential regulator of lymphopoiesis and immune homeostasis, has been implicated in the development of childhood acute lymphoblastic leukemia (C-ALL). Because recent genome-wide association (GWA) studies have linked a region of the 3′-UTR of IKZF1 with C-ALL susceptibility, we tested whether IKZF1 is associated with the autoimmune disease type 1 diabetes. RESEARCH DESIGN AND METHODS rs10272724 (T>C) near IKZF1 at 7p12 was genotyped in 8,333 individuals with type 1 diabetes, 9,947 control subjects, and 3,997 families of European ancestry. Association was tested using logistic regression in the case-control data and by the transmission disequilibrium test in the families. Expression data for IKZF1 by rs10272724 genotype were obtained using quantitative PCR of mRNA/cDNA generated from peripheral blood mononuclear cells from 88 individuals, whereas expression data for five other neighboring genes were obtained from the online Genevar dataset. RESULTS The minor allele of rs10272724 (C) was found to be protective from type 1 diabetes (odds ratio 0.87 [95% CI 0.83–0.91]; P = 1.1 × 10−11). rs10272724 was not correlated with levels of two transcripts of IKZF1 in peripheral blood mononuclear cells. CONCLUSIONS The major susceptibility genotype for C-ALL confers protection from type 1 diabetes. Our finding strengthens the link between autoimmunity and lymphoid cancers. Further investigation is warranted for the genetic effect marked by rs10272724, its impact on IKZF1, and the role of Ikaros and other family members, Ailios (IKZF3) and Eos (IKZF4), in autoimmunity. PMID:21270240

  18. Motor nervous pathway function is impaired after treatment of childhood acute lymphoblastic leukemia: a study with motor evoked potentials.

    Science.gov (United States)

    Harila-Saari, A H; Huuskonen, U E; Tolonen, U; Vainionpää, L K; Lanning, B M

    2001-03-01

    The objective was to evaluate whether motor nervous pathways are affected when patients are treated for childhood acute lymphoblastic leukemia (ALL). Thirty-two children with ALL were studied at the end of treatment by means of motor evoked potentials (MEPs) elicited by magnetic stimulation (MS) transcranially and peripherally and underwent a detailed neurological examination. Thirty-two healthy children matched with them for age, sex, and height served as a control group. The latencies of the MEPs were significantly prolonged along the entire motor nervous pathway in the patients with ALL compared with the healthy controls, indicating demyelination in the thick motor fibres. The MEP amplitudes of the distal extremities elicited by stimulation at the brachial plexus and LV spinal level were significantly lowered in the patients treated for ALL, also indicating anatomical or functional loss of descending motor fibres and/or muscle fibres. The MEP amplitudes elicited by cortical MS showed wider variation and no clear abnormalities were found. Neurological signs and symptoms were common after treatment: 41% of the patients had depressed deep tendon reflexes, 31% had fine motor difficulties and 63% gross motor difficulties, and 34% had dysdiadochokinesia. The conduction delay within the peripheral nerve was related to the post-therapeutic interval after administration of vincristine and the lesions within the CNS to the number of injections of intrathecal methotrexate. The present results show adverse effects of the ALL treatment on the entire motor nervous pathways. In our experience, the measurement of MEPs by MS provides an objective, painless, and practical tool for assessing the treatment-related neurotoxicity in both the CNS and the peripheral nerves. These disturbances in the motor nervous pathways at the end of treatment raise the question of the long-term effects of ALL treatment on the motor nerve tracts, and have led us to employ MEPs to study these effects

  19. Hypothalamic-pituitary-adrenal (HPA) axis suppression after treatment with glucocorticoid therapy for childhood acute lymphoblastic leukaemia.

    Science.gov (United States)

    Rensen, Niki; Gemke, Reinoud Jbj; van Dalen, Elvira C; Rotteveel, Joost; Kaspers, Gertjan Jl

    2017-11-06

    Glucocorticoids play a major role in the treatment of acute lymphoblastic leukaemia (ALL). However, supraphysiological doses can suppress the hypothalamic-pituitary-adrenal (HPA) axis. HPA axis suppression resulting in reduced cortisol response may cause an impaired stress response and an inadequate host defence against infection, which remain a cause of morbidity and death. Suppression commonly occurs in the first days after cessation of glucocorticoid therapy, but the exact duration is unclear. This review is the second update of a previously published Cochrane review. To examine the occurrence and duration of HPA axis suppression after (each cycle of) glucocorticoid therapy for childhood ALL. We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 11), MEDLINE/PubMed (from 1945 to December 2016), and Embase/Ovid (from 1980 to December 2016). In addition, we searched reference lists of relevant articles, conference proceedings (the International Society for Paediatric Oncology and the American Society of Clinical Oncology from 2005 up to and including 2016, and the American Society of Pediatric Hematology/Oncology from 2014 up to and including 2016), and ongoing trial databases (the International Standard Registered Clinical/Social Study Number (ISRCTN) register via http://www.controlled-trials.com, the National Institutes of Health (NIH) register via www.clinicaltrials.gov, and the International Clinical Trials Registry Platform (ICTRP) of the World Health Organization (WHO) via apps.who.int/trialsearch) on 27 December 2016. All study designs, except case reports and patient series with fewer than 10 children, examining effects of glucocorticoid therapy for childhood ALL on HPA axis function. Two review authors independently performed study selection. One review author extracted data and assessed 'Risk of bias'; another review author checked this information. We identified 10 studies (total of 298 children; we identified two studies

  20. MR imaging and ultrasonography findings of early myositis ossificans: a case report

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    Lee, Kyung Ryeol [Jeju National University Hospital, Department of Radiology, Jeju-si, Jeju Special Self-Governing Province (Korea, Republic of); Park, So Young; Jin, Wook [Kyung Hee University Hospital at Gangdong, Department of Radiology, Seoul (Korea, Republic of); Won, Kyu Yeoun [Kyung Hee University Hospital at Gangdong, Department of Pathology, Seoul (Korea, Republic of)

    2016-10-15

    Myositis ossificans (MO) is a benign soft tissue lesion with non-neoplastic heterotopic bone formation. MO in the intermediate and mature stages can be easily diagnosed if characteristic imaging findings such as a peripheral zonal pattern of ossification with variable thickness is observed. However, it is difficult to correctly diagnose early MO because it can mimic malignancy clinically, radiologically, and histopathologically. We report a case of early pseudosarcomatous phase of non-traumatic MO with atypical imaging findings. A 59-year-old woman presented with pain followed by a mass in the left thigh within a week. MR imaging and ultrasonography showed an intramuscular lesion with preserved muscle fascicles in the vastus lateralis muscle. Intralesional ossification or calcification was not seen on ultrasonography. A diagnosis of myositis ossificans was made by ultrasonographically guided biopsy. (orig.)

  1. [Ocular myositis as a rare cause of vision loss].

    Science.gov (United States)

    Rollnik, J D; Requadt, H

    2017-04-01

    Ocular myositis is a rare disease characterized by painful diplopia but loss of vision rarely occurs. The article reviews the literature focusing on the differential diagnostics. We report the case of an 80-year-old women suffering from slowly progressive loss of vision in the left eye. Diplopia was only present at the beginning and there was only moderate pain. Computed tomography and magnetic resonance imaging revealed a swelling of the left medial, lateral and inferior rectus muscles of the orbit leading to compression of the optic nerve in the orbital cone. An intravenous prednisolone stoss therapy (1000 mg per day for 3 consecutive days) was initiated, followed by oral medication of 100 mg per day then tapering over 10 weeks. Vision improved and no relapses were observed. Physicians should be aware of this rare disease to ensure quick diagnosis and treatment of ocular myositis.

  2. A case of parosteal osteosarcoma with a rare complication of myositis ossificans

    Directory of Open Access Journals (Sweden)

    Spinelli Maria Silvia

    2012-11-01

    Full Text Available Abstract We report the case of a parosteal osteosarcoma of the distal ulna, treated with wide resection without reconstruction. The patient developed lung metastasis and a mass in the interosseus membrane of the forearm proximally to the osteotomy. The lung mass was found to be a metastasis from parosteal osteosarcoma and the biopsy of the forearm mass revealed a myositis ossificans. The suspicion of a recurrence of parosteal osteosarcoma, already metastatic, led to a second wide resection with no reconstruction. A slice of the radial cortex was taken during this second procedure. From a histological point of view, good margins were achieved and diagnosis of myositis ossificans was confirmed. Two months later, a radius fracture occurred and a synthesis, with plate and screws, as added with poly(methyl methacrylate (PMMA to reconstruct the bone loss, was performed. Indication of the reconstructive technique and the complication after distal ulna resection in oncologic surgery are discussed in this paper.

  3. Heterotopic ossification (myositis ossificans) in acquired immune deficiency syndrome. Detection by gallium scintigraphy.

    Science.gov (United States)

    Drane, W E; Tipler, B M

    1987-06-01

    A case of heterotopic ossification (myositis ossificans) secondary to the central nervous system complications of acquired immune deficiency syndrome (AIDS) is reported. Because of the overwhelming suspicion of infection in this patient, this diagnosis was not considered until a gallium scan revealed the typical findings of heterotopic ossification. Because of the increasing utilization of gallium imaging in the AIDS population, every imaging specialist should be aware of this potential disorder.

  4. A rare case of Enterococcus faecalis-induced orbital cellulitis and myositis

    Directory of Open Access Journals (Sweden)

    Piyush Kohli

    2016-01-01

    Full Text Available Orbital cellulitis is an infection of soft tissue behind the orbital septum. Common pathogens isolated include Staphylococcus aureus, Staphylococcus epidermidis, and Streptococcus pneumoniae. It is a straightforward diagnosis and usually responds to empirical treatment without any sequela. We report a case of orbital cellulitis caused by Enterococcus faecalis, which was complicated by myositis of levator palpebrae superioris. To the best of our knowledge, only one case report exists dating way back to 1986.

  5. A rare case of Enterococcus faecalis-induced orbital cellulitis and myositis.

    Science.gov (United States)

    Kohli, Piyush; Ichhpujani, Parul; Bansal, Rakesh Kumar; Kumar, Suresh

    2016-08-01

    Orbital cellulitis is an infection of soft tissue behind the orbital septum. Common pathogens isolated include Staphylococcus aureus, Staphylococcus epidermidis, and Streptococcus pneumoniae. It is a straightforward diagnosis and usually responds to empirical treatment without any sequela. We report a case of orbital cellulitis caused by Enterococcus faecalis, which was complicated by myositis of levator palpebrae superioris. To the best of our knowledge, only one case report exists dating way back to 1986.

  6. A rare case of Enterococcus faecalis-induced orbital cellulitis and myositis

    OpenAIRE

    Piyush Kohli; Parul Ichhpujani; Rakesh Kumar Bansal; Suresh Kumar

    2016-01-01

    Orbital cellulitis is an infection of soft tissue behind the orbital septum. Common pathogens isolated include Staphylococcus aureus, Staphylococcus epidermidis, and Streptococcus pneumoniae. It is a straightforward diagnosis and usually responds to empirical treatment without any sequela. We report a case of orbital cellulitis caused by Enterococcus faecalis, which was complicated by myositis of levator palpebrae superioris. To the best of our knowledge, only one case report exists dating wa...

  7. Cervical necrotizing fasciitis and myositis in a western lowland gorilla (Gorilla gorilla gorilla).

    Science.gov (United States)

    Allender, M C; McCain, S L; Ramsay, E C; Schumacher, J; Ilha, M R S

    2009-06-01

    A 39-yr-old wild-caught, female western lowland gorilla (Gorilla gorilla gorilla) died during an immobilization to assess swelling and apparent pain of the cervical region. Necropsy revealed a fistulous tract containing plant material in the oropharynx, above the soft palate, communicating with a left-sided cervical necrotizing fasciitis and myositis. Alpha-hemolytic Streptococcus and Prevotella sp. were isolated from the cervical lesion. This is a report of cervical necrotizing fasciitis in a western lowland gorilla.

  8. Vaccine-induced myositis with intramuscular sterile abscess formation: MRI and ultrasound findings

    Energy Technology Data Exchange (ETDEWEB)

    Polat, Ahmet Veysel; Bekci, Tumay; Selcuk, Mustafa Bekir [Ondokuz Mayis University, Department of Radiology, Faculty of Medicine, Samsun (Turkey); Dabak, Nevzat [Ondokuz Mayis University, Department of Orthopaedics and Traumatology, Faculty of Medicine, Samsun (Turkey); Ulu, Esra Meltem Kayahan [Samsun Medical Park Hospital, Department of Radiology, Samsun (Turkey)

    2015-12-15

    Although limb swelling is a well-known complication of vaccination, its rarity and wide band of differential diagnosis of limb swelling make it a diagnostic challenge. In this case report, we describe three cases of vaccine-induced myositis with intramuscular sterile abscess formation in patients with limb swelling and their magnetic resonance imaging and ultrasonography findings. Both radiologists and clinicians should be familiar with this rare entity, its clinical and imaging spectrum, and follow-up strategies. (orig.)

  9. The association of reduced folate carrier 80G>A polymorphism to outcome in childhood acute lymphoblastic leukemia interacts with chromosome 21 copy number

    DEFF Research Database (Denmark)

    Gregers, Jannie; Christensen, Ib Jarle; Dalhoff, Kim

    2010-01-01

    with chromosome 21 copy number in the leukemic clone. A total of 500 children with acute lymphoblastic leukemia treated according to the common Nordic treatment protocols were included, and we found that the RFC AA variant was associated with a 50% better chance of staying in remission compared with GG or GA......The reduced folate carrier (RFC) is involved in the transport of methotrexate (MTX) across the cell membrane. The RFC gene (SLC19A1) is located on chromosome 21, and we hypothesized that the RFC80 G>A polymorphism would affect outcome and toxicity in childhood leukemia and that this could interact...

  10. Interphase fluorescent in situ hybridization deletion analysis of the 9p21 region and prognosis in childhood acute lymphoblastic leukaemia (ALL)

    DEFF Research Database (Denmark)

    Kuchinskaya, Ekaterina; Heyman, Mats; Nordgren, Ann

    2011-01-01

    Interphase fluorescent in situ hybridization (FISH) was applied on diagnostic BM smears from 519 children with acute lymphoblastic leukaemia (ALL) in order to establish the frequency and prognostic importance of 9p21 deletion in children enrolled in the Nordic Society of Paediatric Haematology...... of 9p21. In conclusion, in this large series of childhood ALL deletion of 9p21 was not associated with worse prognosis. However, interphase FISH deletion analysis of 9p21 could be used as a first step to detect unfavourable subtle cytogenetic aberrations such as the dic(9;20) rearrangement....

  11. Residual disease detected by flow cytometry is an independent predictor of survival in childhood acute myeloid leukaemia; results of the NOPHO-AML 2004 study

    DEFF Research Database (Denmark)

    Tierens, Anne; Bjørklund, Elizabeth; Siitonen, Sanna

    2016-01-01

    Early response after induction is a prognostic factor for disease outcome in childhood acute myeloid leukaemia (AML). Residual disease (RD) detection by multiparameter flow cytometry (MFC) was performed at day 15 and before consolidation therapy in 101 patients enrolled in the Nordic Society...... of Paediatric Haemato-Oncology AML 2004 study. A multicentre laboratory approach to RD analysis was used. Event-free survival (EFS) and overall survival (OS) was significantly different in patients with and without RD at both time points, using a 0·1% RD cut-off level. RD-negative and -positive patients after...

  12. Clinical Manifestations and Myositis-Specific Autoantibodies Associated with Physical Dysfunction after Treatment in Polymyositis and Dermatomyositis: An Observational Study of Physical Dysfunction with Myositis in Japan

    Directory of Open Access Journals (Sweden)

    Hidenaga Kawasumi

    2016-01-01

    Full Text Available Objective. The physical function of PM/DM patients after remission induction therapy remains unknown adequately. The aim of our study was to evaluate the present status of physical dysfunction and to clarify the clinical manifestations and myositis-specific autoantibodies (MSAs associated with physical dysfunction after treatment in PM/DM. Methods. We obtained clinical data including the age at disease onset, gender, disease duration, laboratory data prior to initial treatment, and the specific treatment administered. We evaluated disease activity and physical dysfunction after treatment using the core set provided by the International Myositis Assessment and Clinical Studies Group. Results. 57% of the 77 enrolled patients with PM/DM had troubles in daily living after treatment. At the enrolment, disease activity evaluated by physicians was only revealed in 20% of patients. In a multivariate analysis, the age at disease onset, female gender, and CK levels before treatment were significantly associated with the severity of physical dysfunction after treatment. Anti-SRP positivity was associated with more severe physical dysfunction after treatment than anti-ARS or anti-MDA5. Conclusions. Half of the PM/DM patients showed physical dysfunction after treatment. Age at disease onset, gender, CK level before treatment, and anti-SRP were significant predictors associated with physical dysfunction after treatment in PM/DM.

  13. A comparison of peripheral blood and buffy coat smear examination for the prediction of bone marrow relapse of acute lymphoblastic leukaemia in childhood.

    Science.gov (United States)

    Franklin, I M

    1983-02-01

    In an attempt to see if buffy coat smear examination might be an alternative to bone marrow aspiration for predicting relapse, 98 consecutive bone marrow aspirates from 96 children with acute lymphoblastic leukaemia were examined blind with buffy coat and peripheral blood from the same patients. The 28 bone marrow aspirates from children no longer on treatment were all normal, and routine aspirates would appear unjustified in these patients. Eight of the remaining marrows showed relapse, but only three were not predicted from the peripheral blood and buffy coat. In no case was buffy coat superior to peripheral blood in the detection of bone marrow relapse. Routine bone marrow aspirates are an inefficient way of diagnosing relapse in acute lymphoblastic leukaemia in childhood, despite their precision, and a prospective study is needed to determine their value.

  14. Support for social rehabilitation of childhood acute lymphoblastic leukemia patients. Psychological and educational assessment by the K-ABC

    Energy Technology Data Exchange (ETDEWEB)

    Izumi, Mayuko [Ochanomizu Univ., Tokyo (Japan); Hosoya, Ryouta; Oohira, Mutsuro; Kaneko, Takashi; Matsushita, Taketsugu

    2000-10-01

    Intellectual impairment in pediatric acute lymphoblastic leukemia (ALL) is thought to be caused by the effect of treatment on the central nervous system. We therefore assessed the characteristics and tendencies of patients' cognitive ability by using the K-ABC (Kaufman Assessment Battery for Children), an intelligence test. The subjects were 28 patients treated for ALL (males 18, females 10, age 4.7-12.0 years). The patients who took the K-ABC test were divided into irradiation group (15 patients who received brain irradiation as prophylactic treatment) and a non-irradiation group (13 patients whose brain was not irradiated), and evaluated the results. The K-ABC consists of a cognition processing scale and an acquisition level, and the cognition processing scale consists of a sequential processing scale and simultaneous processing scale. Patients were assessed in regard to various factors: 1. sex, 2. age of onset, 3. length of hospital stay, 4. age at the time of irradiation, 5. radiation dose, 6. score on the cognition processing scale, and multiple comparisons were made based on analysis of variance, least significant differences (1, 2, 3, 6), and the t-test (4, 5). Sequential processing ability was impaired in the patients with impaired cognitive processing in both groups. Part of simultaneous processing ability (ability to understand spatial relationships) tended to be reduced in the irradiation group in addition to the impairment in sequential processing ability, and factors 1 and 4 influenced cognitive ability in the irradiation group. The ability of girls decreased more than in boys. When children were irradiated below 4 years of age, their ability decreased even more. Regardless of whether they had received radiation therapy, all of the patients had received chemotherapy, including methotrexate, etc., and the anticancer drugs may have reduced their cognitive ability. The reduction of simultaneous processing ability may have been caused by the addition

  15. Association of methylenetetrahytrofolate reductase (MTHFR) C677T and A1298C polymorphisms with the susceptibility of childhood acute lymphoblastic leukaemia (ALL) in Chinese population.

    Science.gov (United States)

    Li, Xiaolei; Liao, Qingchuan; Zhang, Shunguo; Chen, Minling

    2014-01-29

    The aim of this study was to investigate the relationship between the polymorphisms of the methylenetetrahytrofolate reductase (MTHFR) gene and susceptibility to childhood acute lymphoblastic leukemia (ALL). A case-control study was conducted among 98 children with ALL and 93 age- and sex- matched non-ALL controls. Genotyping of MTHFR C677T and A1298C polymorphisms was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The odds ratios (ORs) of MTHFR genotypes were used to assess the associations of these polymorphisms with childhood ALL susceptibility. No significant differences were observed for frequencies of the 677CC, 677CT and 677TT genotypes between patients and controls. Frequencies of the 1298AA, 1298 AC and 1298CC genotypes between the two groups were significantly different. The risk of ALL with the 1298C allele carriers (AC + CC) was elevated by 1.1 times compared with the AA genotype [OR = 2.100; 95% CI (1.149; 3.837); P = 0.015]. The MTHFR A1298C polymorphism is associated with susceptibility to childhood ALL in the Chinese population.

  16. Randomized double blind trial of ciprofloxacin prophylaxis during induction treatment in childhood acute lymphoblastic leukemia in the WK-ALL protocol in Indonesia

    Directory of Open Access Journals (Sweden)

    Widjajanto PH

    2013-02-01

    Full Text Available Pudjo H Widjajanto,1 Sumadiono Sumadiono,1 Jacqueline Cloos,2,3 Ignatius Purwanto,1 Sutaryo Sutaryo,1 Anjo JP Veerman1,21Pediatric Hematology and Oncology Division, Department of Pediatrics, Dr Sardjito Hospital, Medical Faculty, Universitas Gadjah Mada, Yogyakarta, Indonesia; 2Pediatric Oncology/Hematology Division, Department of Pediatrics, 3Department of Hematology, VU University Medical Center, Amsterdam, The NetherlandsObjectives: Toxic death is a big problem in the treatment of childhood acute lymphoblastic leukemia (ALL, especially in low-income countries. Studies of ciprofloxacin as single agent prophylaxis vary widely in success rate. We conducted a double-blind, randomized study to test the effects of ciprofloxacin monotherapy as prophylaxis for sepsis and death in induction treatment of the Indonesian childhood ALL protocol.Methods: Patients were randomized to the ciprofloxacin arm (n = 58 and to the placebo arm (n = 52. Oral ciprofloxacin monotherapy or oral placebo was administered twice a day. All events during induction were recorded: toxic death, abandonment, resistant disease, and complete remission rate.Results: Of 110 patients enrolled in this study, 79 (71.8% achieved CR. In comparison to the placebo arm, the ciprofloxacin arm had lower nadir of absolute neutrophil count during induction with median of 62 (range: 5–884 versus 270 (range: 14–25,480 × 109 cells/L (P > 0.01, greater risks for experiencing fever (50.0% versus 32.7%, P = 0.07, clinical sepsis (50.0% versus 38.5%, P = 0.22, and death (18.9% versus 5.8%, P = 0.05.Conclusion: In our setting, a reduced intensity protocol in a low-income situation, the data warn against using ciprofloxacin prophylaxis during induction treatment. A lower nadir of neutrophil count and higher mortality were found in the ciprofloxacin group.Keywords: ciprofloxacin, prophylaxis, childhood acute lymphoblastic leukemia, randomized trial, low-income country

  17. Differences in meiotic recombination rates in childhood acute lymphoblastic leukemia at an MHC class II hotspot close to disease associated haplotypes.

    Directory of Open Access Journals (Sweden)

    Pamela Thompson

    Full Text Available Childhood Acute Lymphoblastic Leukemia (ALL is a malignant lymphoid disease of which B-cell precursor- (BCP and T-cell- (T ALL are subtypes. The role of alleles encoded by major histocompatibility loci (MHC have been examined in a number of previous studies and results indicating weak, multi-allele associations between the HLA-DPB1 locus and BCP-ALL suggested a role for immunosusceptibility and possibly infection. Two independent SNP association studies of ALL identified loci approximately 37 kb from one another and flanking a strong meiotic recombination hotspot (DNA3, adjacent to HLA-DOA and centromeric of HLA-DPB1. To determine the relationship between this observation and HLA-DPB1 associations, we constructed high density SNP haplotypes of the 316 kb region from HLA-DMB to COL11A2 in childhood ALL and controls using a UK GWAS data subset and the software PHASE. Of four haplotype blocks identified, predicted haplotypes in Block 1 (centromeric of DNA3 differed significantly between BCP-ALL and controls (P = 0.002 and in Block 4 (including HLA-DPB1 between T-ALL and controls (P = 0.049. Of specific common (>5% haplotypes in Block 1, two were less frequent in BCP-ALL, and in Block 4 a single haplotype was more frequent in T-ALL, compared to controls. Unexpectedly, we also observed apparent differences in ancestral meiotic recombination rates at DNA3, with BCP-ALL showing increased and T-ALL decreased levels compared to controls. In silico analysis using LDsplit sotware indicated that recombination rates at DNA3 are influenced by flanking loci, including SNPs identified in childhood ALL association studies. The observed differences in rates of meiotic recombination at this hotspot, and potentially others, may be a characteristic of childhood leukemia and contribute to disease susceptibility, alternatively they may reflect interactions between ALL-associated haplotypes in this region.

  18. Severe childhood malnutrition

    DEFF Research Database (Denmark)

    Bhutta, Zulfiqar A; Berkley, James A; Bandsma, Robert H J

    2017-01-01

    The main forms of childhood malnutrition occur predominantly in children ... nutritional status and suboptimal nutritional intake in infancy and early childhood. Children with severe malnutrition have an increased risk of serious illness and death, primarily from acute infectious diseases. International growth standards are used for the diagnosis of severe malnutrition and provide...

  19. Multiple drug resistance protein (MDR-1, multidrug resistance-related protein (MRP and lung resistance protein (LRP gene expression in childhood acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    Elvis Terci Valera

    Full Text Available CONTEXT: Despite the advances in the cure rate for acute lymphoblastic leukemia, approximately 25% of affected children suffer relapses. Expression of genes for the multiple drug resistance protein (MDR-1, multidrug resistance-related protein (MRP, and lung resistance protein (LRP may confer the phenotype of resistance to the treatment of neoplasias. OBJECTIVE: To analyze the expression of the MDR-1, MRP and LRP genes in children with a diagnosis of acute lymphoblastic leukemia via the semiquantitative reverse transcription polymerase chain reaction (RT-PCR, and to determine the correlation between expression and event-free survival and clinical and laboratory variables. DESIGN: A retrospective clinical study. SETTING: Laboratory of Pediatric Oncology, Department of Pediatrics, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Brazil. METHODS: Bone marrow aspirates from 30 children with a diagnosis of acute lymphoblastic leukemia were assessed for the expression of messenger RNA for the MDR-1, MRP and LRP genes by semi-quantitative RT-PCR. RESULTS: In the three groups studied, only the increased expression of LRP was related to worsened event-free survival (p = 0.005. The presence of the common acute lymphoblastic leukemia antigen (CALLA was correlated with increased LRP expression (p = 0.009 and increased risk of relapse or death (p = 0.05. The relative risk of relapse or death was six times higher among children with high LRP expression upon diagnosis (p = 0.05, as confirmed by multivariate analysis of the three genes studied (p = 0.035. DISCUSSION: Cell resistance to drugs is a determinant of the response to chemotherapy and its detection via RT-PCR may be of clinical importance. CONCLUSIONS: Evaluation of the expression of genes for resistance to antineoplastic drugs in childhood acute lymphoblastic leukemia upon diagnosis, and particularly the expression of the LRP gene, may be of clinical relevance, and should be the

  20. Ultraviolet Radiation Exposure is Associated with Clinical and Autoantibody Phenotypes in Juvenile Myositis

    Science.gov (United States)

    Shah, Mona; Targoff, Ira N.; Rice, Madeline M.; Miller, Frederick W.; Rider, Lisa G.

    2013-01-01

    Objective Genetic and environmental factors may contribute to the etiology of the juvenile idiopathic inflammatory myopathies (JIIM), systemic autoimmune diseases characterized by muscle and skin inflammation. We investigated the association between ultraviolet radiation (UVR) exposure and the clinical and autoantibody expression of JIIM. Methods We assessed the relationship between UVR exposure in the month before symptom onset and prevalence of juvenile dermatomyositis (JDM) versus polymyositis (JPM) in 298 patients. Among JDM patients, the association between UVR exposure and myositis autoantibodies was assessed. Regression models were stratified by sex and race. The association between regional UV index in U.S. geoclimatic zones and the clinical and autoantibody subgroups was examined by weighted least squares regression analysis. Results We observed increasing odds of JDM compared with JPM per unit increase in the patients’ highest UV index in the month before symptom onset in girls (OR = 1.18; 95% CI = 1.00–1.40). The average and highest UV indices were associated with increasing odds of anti-p155/140 autoantibodies, which was strongest in white males (OR 1.30 and 1.23, respectively). No association was observed between the UV index and anti-MJ autoantibodies or patients without myositis autoantibodies. Across US geoclimatic regions, the average UV index was associated with increasing odds of JDM and anti-p155/140 autoantibodies but decreasing odds of anti-MJ autoantibodies. Conclusion Short-term UVR exposure prior to illness onset may have a role in the clinical and serologic expression of juvenile myositis. Research examining mechanisms of UVR in JIIM pathogenesis is suggested from these findings. PMID:23658122

  1. Avulsion Fracture and Myositis Ossificans in a Professional Teenage Dancer: A Case Report.

    Science.gov (United States)

    Tosun, Ozgur; Koralp, Muhabbet D; Tosun, Aliye; Celebi, Levent; Bulakbaşi, Nail

    2015-06-01

    Fractures of the transverse processes in the lumbar vertebrae occur as the result of major forces such as direct blunt trauma, violent lateral flexion-extension forces, avulsion of the psoas muscle, or Malgaigne fractures of the pelvis. Dancers make repeated and forceful hyperextension and flexions of the spine, which may cause fractures of the transverse processes of the lumbar vertebrae. Repeated trauma of muscles in dancers may cause avulsion fractures and myositis ossificans. Herein, we report MRI and CT findings of an avulsion from the right transverse process of the L2 and L3 vertebrae in a 16-year-old professional teenage dancer, who responded to conservative treatment.

  2. NEUTROPHILIC MYOSITIS ASSOCIATED WITH PYODERMA GANGRENOSUM IN A BREAK-DANCER

    Directory of Open Access Journals (Sweden)

    Hisashi Tamiya

    2013-10-01

    Full Text Available Neutrophilic myositis is an extremely rare condition, cases of which have been reported in association with neutrophilic dermatosis, inflammatory bowel disease and malignant hematological disease. The disorder is histologically characterized by a sterile infiltration of neutrophils throughout muscle, with necrosis of muscle fibres. We here report the case of a young male who also had associated pyoderma gangrenosum, and who presented with necrotizing fasciitis-like manifestations. In this case, although there were no other underlying disorders, compulsive exertional stress due to break-dancing was thought to be a precipitant. Debridement of the necrotic tissues combined with oral corticosteroid treatment was effective.

  3. Proliferative myositis of the latissimus dorsi presenting in a 20-year-old male athlete

    LENUS (Irish Health Repository)

    Mc Hugh, N

    2017-08-01

    We describe the case of a 20-year-old rower presenting with an uncommon condition of Proliferative Myositis (PM) affecting the Latissimus Dorsi (LD). PM is a rare, benign tumour infrequently developing in the upper back. Its rapid growth and firm consistency may mistake it for sarcoma at presentation. Therefore, careful multidisciplinary work-up is crucial, and should involve appropriate radiological and histopathological investigations. Here, we propose the aetiology of LD PM to be persistent myotrauma induced by repetitive rowing motions. Symptoms and rate of progression ultimately determine the management which includes surveillance and\\/or conservative resection. There have been no documented cases of recurrence or malignant transformation.

  4. A Unique Case of Muscle Invasive Metastatic Breast Cancer Mimicking Myositis

    Science.gov (United States)

    2017-06-28

    TYPE 08/ 03/20 17 Publ ication/Journal 4. TITLE AND SUBTITLE A unique case of muscle-invasive metastatic breast cancer mimicking myositis 6...Rev. 8/98) Prescnbed by ANSI Std Z39. 18 Adobe Profes11on11 7.0 Title: A Unique Case of M uscle-Invasive Metastatic Breast Cancer M imicking...an 84-year-old female who presented with neck swelling and upper airway obstruction due to metastatic breast cancer invading the sternocleidomastoid

  5. Extraskeletal osteosarcoma arising in myositis ossificans: a case report and review of the literature.

    Science.gov (United States)

    Savant, Deepika; Kenan, Shachar; Kenan, Samuel; Kahn, Leonard

    2017-08-01

    We report a case of a 23-year-old female with pain and fullness in the right popliteal fossa. An MRI scan demonstrated an ossified enhancing soft tissue mass. Evaluation of the resected specimen showed a high-grade extraskeletal osteosarcoma juxtaposed to the three zones of myositis ossificans. At 1-year follow-up the patient is alive and disease free. A review of the literature purporting to document such an association failed to demonstrate a single case in which an osteosarcoma and MO with its zonal architecture co-existed.

  6. Inflammatory myositis complicating hypocomplementemic urticarial vasculitis despite on-going immunosuppression.

    Science.gov (United States)

    Chew, Gary Y J; Gatenby, Paul A

    2007-08-01

    We present a patient with previously diagnosed hypocomplementemic urticarial vasculitis syndrome, with skin, lung, and renal involvement, who presented with congestive cardiac failure. During the course of her hospitalization, she was also found to have profound proximal muscle weakness in both upper and lower limbs associated with raised creatinine kinase levels. A muscle biopsy was performed, which demonstrated evidence of an inflammatory myositis with vasculitis, which had returned despite on-going immunosuppression. This occurrence of a new autoimmune disease may well be an example of the "waste disposal" hypothesis.

  7. Cured meat, vegetables, and bean-curd foods in relation to childhood acute leukemia risk: A population based case-control study

    Directory of Open Access Journals (Sweden)

    Su Li

    2009-01-01

    Full Text Available Abstract Background Consumption of cured/smoked meat and fish leads to the formation of carcinogenic N-nitroso compounds in the acidic stomach. This study investigated whether consumed cured/smoked meat and fish, the major dietary resource for exposure to nitrites and nitrosamines, is associated with childhood acute leukemia. Methods A population-based case-control study of Han Chinese between 2 and 20 years old was conducted in southern Taiwan. 145 acute leukemia cases and 370 age- and sex-matched controls were recruited between 1997 and 2005. Dietary data were obtained from a questionnaire. Multiple logistic regression models were used in data analyses. Results Consumption of cured/smoked meat and fish more than once a week was associated with an increased risk of acute leukemia (OR = 1.74; 95% CI: 1.15–2.64. Conversely, higher intake of vegetables (OR = 0.55; 95% CI: 0.37–0.83 and bean-curd (OR = 0.55; 95% CI: 0.34–0.89 was associated with a reduced risk. No statistically significant association was observed between leukemia risk and the consumption of pickled vegetables, fruits, and tea. Conclusion Dietary exposure to cured/smoked meat and fish may be associated with leukemia risk through their contents of nitrites and nitrosamines among children and adolescents, and intake of vegetables and soy-bean curd may be protective.

  8. Intensive treatment of children with acute lymphoblastic leukemia according to ALL-BFM-86 without cranial radiotherapy : Results of Dutch Childhood Leukemia Study Group protocol ALL-7 (1988-1991)

    NARCIS (Netherlands)

    Kamps, WA; Bokkerink, JPM; Hahlen, K; Hermans, J; Riehm, H; Gadner, H; Schrappe, M; Slater, R; van den Berg-de Ruiter, E; Smets, LA; de Vaan, GAM; Weening, RS; van Weerden, JF; van Wering, ER; van der Does-van den Berg, A

    1999-01-01

    In The Netherlands from July 1988 to October 1991, children (0 to 16 years of age) with de novo acute lymphoblastic leukemia (ALL) were treated according to protocol ALL-7 of the Dutch Childhood Leukemia Study Group (DCLSG). In this protocol, chemotherapy and treatment stratification were identical

  9. Combination Chemotherapy With or Without Bone Marrow Transplantation in Treating Children With Acute Myelogenous Leukemia or Myelodysplastic Syndrome

    Science.gov (United States)

    2013-01-15

    Childhood Acute Erythroleukemia (M6); Childhood Acute Megakaryocytic Leukemia (M7); Childhood Acute Monoblastic Leukemia (M5a); Childhood Acute Monocytic Leukemia (M5b); Childhood Acute Myeloblastic Leukemia With Maturation (M2); Childhood Acute Myeloblastic Leukemia Without Maturation (M1); Childhood Acute Myelomonocytic Leukemia (M4); Childhood Myelodysplastic Syndromes; Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndromes; Refractory Anemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Refractory Anemia With Ringed Sideroblasts; Secondary Myelodysplastic Syndromes; Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

  10. Vitamin D and bone minerals status in the long-term survivors of childhood acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    Nahid Reisi

    2015-01-01

    Conclusions: ALL treatment is associated with the increase in prevalence of vitamin D insufficiency in the childhood ALL survivors and since the low vitamin D level potentially increases the risk of low bone density, subsequent malignancies, and cardiovascular disease in the survivors, close follow-up of such patients are highly recommended to prevent the stated complications.

  11. Gene Dose Effects of GSTM1, GSTT1 and GSTP1 Polymorphisms on Outcome in Childhood Acute Lymphoblastic Leukemia

    DEFF Research Database (Denmark)

    Borst, Louise; Buchard, Anders; Rosthoj, Susanne

    2012-01-01

    were applied for genotyping the GSTM1 and GSTT1 genes (distinguishing between 0, 1, or 2 gene copies) and the GSTP1 313 A>G polymorphism, simultaneously. A total of 263 childhood ALL patients were genotyped. No gene dose effect on outcome was demonstrated with either GST polymorphisms. Grouping of GSTM...

  12. Herpes Zoster Ophthalmicus Presenting as Acute Orbital Myositis Preceding a Skin Rash: A Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Oh, Ha Yeun; Cho, Seong Whi [Dept. of Radiology, Kangwon National University Hospital, Chuncheon (Korea, Republic of); Kim, Sung Hun [Dept. of Neurology, Kangwon National University Hospital, Chuncheon (Korea, Republic of)

    2012-03-15

    Herpes zoster ophthalmicus, in which orbital symptoms and signs appear before the onset of a skin rash, is very rare. We experienced such a case and therefore report on it via magnetic resonance imaging. A 48-year-old man with pain and swelling of left eye and headache presented 2 days before onset of a zoster skin rash. On orbit-al MRI, edematous thickening of the left lateral rectus muscle with high signal intensity was revealed. After contrast injection, the lateral rectus muscle demonstrated heterogenous enhancement. Also, diffuse contrast enhancement was noted at left preseptal space, lacrimal gland and periorbital soft tissue. The man was treated with antiviral agents and prednisolone. Two weeks later, he recovered from the skin manifestations and most of the orbital manifestations except for the diplopia and restricted lateral movement.

  13. Genomic profiling of thousands of candidate polymorphisms predicts risk of relapse in 778 Danish and German childhood acute lymphoblastic leukemia patients

    DEFF Research Database (Denmark)

    Wesolowska, Agata; Borst, L.; Dalgaard, Marlene Danner

    2015-01-01

    associated with risk of relapse across protocols. SNP and biologic pathway level analyses associated relapse risk with leukemia aggressiveness, glucocorticosteroid pharmacology/response and drug transport/metabolism pathways. Classification and regression tree analysis identified three distinct risk groups......Childhood acute lymphoblastic leukemia survival approaches 90%. New strategies are needed to identify the 10–15% who evade cure. We applied targeted, sequencing-based genotyping of 25 000 to 34 000 preselected potentially clinically relevant singlenucleotide polymorphisms (SNPs) to identify host...... genome profiles associated with relapse risk in 352 patients from the Nordic ALL92/2000 protocols and 426 patients from the German Berlin–Frankfurt–Munster (BFM) ALL2000 protocol. Patients were enrolled between 1992 and 2008 (median follow-up: 7.6 years). Eleven cross-validated SNPs were significantly...

  14. Final height and body mass index in adult survivors of childhood acute lymphoblastic leukemia treated without cranial radiotherapy: a retrospective longitudinal multicenter Italian study.

    Science.gov (United States)

    Bruzzi, Patrizia; Predieri, Barbara; Corrias, Andrea; Marsciani, Alberto; Street, Maria Elisabeth; Rossidivita, Aurora; Paolucci, Paolo; Iughetti, Lorenzo

    2014-09-22

    Young adult survivors of childhood acute lymphoblastic leukemia (ALL) treated with protocols including cranial radiotherapy demonstrate a persistent weight gain and reduced final height. Published reports on the effects on growth of different oncologic therapies are conflicting and difficult to interpret because they combined children treated with both cranial irradiation and multi-agent chemotherapy. Our study investigated the effect of chemotherapy alone on body mass index (BMI) and on growth at the achievement of final height in a homogeneous cohort of Italian childhood ALL survivors. We retrospectively studied 162 Caucasian patients treated on the Italian Association of Pediatric Hematology and Oncology protocols without radiotherapy between 1989 and 2000 at five Italian centers with 107 inclusions (58 males). Height- and BMI-standard deviation score (SDS) were collected at diagnosis of ALL, at the end of treatment and at the achievement of final height. Changes in height SDS and BMI SDS with time were analyzed using dependent sample Student's t-test. A significant reduction of height-SDS was documented during treatment in both genders. This reduction of height-SDS was not followed by an appropriate catch-up growth, despite the achievement of a mean final height within the normal range. At diagnosis females showed a lower mean BMI-SDS than males. During treatment, in the whole population, BMI-SDS increased significantly. After it, while males lost BMI-SDS, females showed its persistent increase. Survivors of childhood ALL generally seemed to achieve a normal final height with a BMI within the normal range. These parameters appeared to be only minimally affected by chemotherapy. Nevertheless, height catch-up growth was not completed after chemotherapy in both genders and all patients experienced an increase of BMI-SDS during chemotherapy that only females seemed to conserve until the achievement of final height.

  15. ARID5B, CEBPE and PIP4K2A Germline Genetic Polymorphisms and Risk of Childhood Acute Lymphoblastic Leukemia in Mexican Patients: A MIGICCL Study.

    Science.gov (United States)

    Bekker-Méndez, Vilma Carolina; Núñez-Enríquez, Juan Carlos; Torres Escalante, José Luis; Alvarez-Olmos, Enrique; González-Montalvoc, Pablo Miguel; Jiménez-Hernández, Elva; Sansón, Aurora Medina; Leal, Yelda A; Ramos-Cervantes, María Teresa; Guerra-Castillo, Francisco Xavier; Ortiz-Maganda, Mónica Patricia; Flores-Lujano, Janet; Pérez-Saldivar, Maria Luisa; Velazquez-Aviña, Martha Margarita; Bolea-Murga, Victoria; Torres-Nava, José Refugio; Amador-Sanchez, Raquel; Solis-Labastida, Karina Anastacia; Rámirez-Bello, Julian; Fragoso, José Manuel; Mejía-Aranguré, Juan Manuel

    2016-11-01

    Childhood acute lymphoblastic leukemia (ALL) is the leading cause of childhood cancer-related deaths worldwide. Multiples studies have shown that ALL seems to be originated by an interaction between environmental and genetic susceptibility factors. The ARID5B polymorphisms are among the most reproducible ALL associated-risk alleles in different populations. The aim of the present study was to examine the contribution of ARID5B, CEBPE, and PIP4K2 risk alleles for the development of ALL in children from Mexico City and Yucatan, Mexico. A study was conducted with a total of 761 unrelated subjects. Two hundred eighty five ALL cases (111 from Yucatan and 174 from Mexico City) and 476 healthy subjects. Genotyping included the rs7088318 (PIP4K2A), rs10821936 (ARID5B), rs7089424 (ARID5B) and rs2239633 (CEBPE) polymorphisms. Associations between ALL and rs10821936 and rs7089424 ARID5B SNPs were found (OR = 1.9, 95% CI (1.5-2.4) and OR = 2.0, 95% CI (1.6-2.5), respectively). Moreover, a higher risk was observed in the homozygous risk genotypes of carriers from Mexico City (OR = 3.1, 95% CI (2.0-4.9) and OR 3.1, CI 95% (2.0-4.8), respectively). Otherwise, the rs7088318 (PIP4K2A) and rs2239633 (CEBPE) polymorphisms were not associated with ALL risk. Our analysis suggests that ARID5B confers risk for childhood ALL in a Mexican population. Copyright © 2016 IMSS. Published by Elsevier Inc. All rights reserved.

  16. Cognitive outcomes among Latino survivors of childhood acute lymphoblastic leukemia and lymphoma: A cross-sectional cohort study using culturally competent, performance-based assessment.

    Science.gov (United States)

    Bava, Laura; Johns, Alexis; Kayser, Kimberly; Freyer, David R

    2017-10-08

    This study sought to characterize cognitive outcomes among Latino survivors of childhood acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LL). In this cross-sectional cohort study, Latino survivors of ALL (n = 57) and LL (n = 5) aged 6-16 years were pooled and evaluated using validated measures of cognitive, academic, and behavioral function and English language proficiency. Performance was compared with norms using single-sample t-tests. In this cohort (n = 62, 50% male), mean ages at diagnosis and testing were 4.5 and 10.8 years, respectively; mean time off treatment was 44.7 months. All participants spoke English and over half (57%) identified Spanish as the primary language in the home. Forty-two families (68%) placed in the two lowest Hollingshead socioeconomic status categories. Participants were below average for working memory (P working memory (P < 0.001) and metacognition (P = 0.014). Similar to other childhood ALL/LL survivors, overall cognitive function in this Latino sample was relatively preserved but selected deficits were observed. Routine cognitive screening is indicated in this population. © 2017 Wiley Periodicals, Inc.

  17. Family-based exome-wide association study of childhood acute lymphoblastic leukemia among Hispanics confirms role of ARID5B in susceptibility.

    Directory of Open Access Journals (Sweden)

    Natalie P Archer

    Full Text Available We conducted an exome-wide association study of childhood acute lymphoblastic leukemia (ALL among Hispanics to confirm and identify novel variants associated with disease risk in this population. We used a case-parent trio study design; unlike more commonly used case-control studies, this study design is ideal for avoiding issues with population stratification bias among this at-risk ethnic group. Using 710 individuals from 323 Guatemalan and US Hispanic families, two inherited SNPs in ARID5B reached genome-wide level significance: rs10821936, RR = 2.31, 95% CI = 1.70-3.14, p = 1.7×10-8 and rs7089424, RR = 2.22, 95% CI = 1.64-3.01, p = 5.2×10-8. Similar results were observed when restricting our analyses to those with the B-ALL subtype: ARID5B rs10821936 RR = 2.22, 95% CI = 1.63-3.02, p = 9.63×10-8 and ARID5B rs7089424 RR = 2.13, 95% CI = 1.57-2.88, p = 2.81×10-7. Notably, effect sizes observed for rs7089424 and rs10821936 in our study were >20% higher than those reported among non-Hispanic white populations in previous genetic association studies. Our results confirmed the role of ARID5B in childhood ALL susceptibility among Hispanics; however, our assessment did not reveal any strong novel inherited genetic risks for acute lymphoblastic leukemia among this ethnic group.

  18. Family-based exome-wide association study of childhood acute lymphoblastic leukemia among Hispanics confirms role of ARID5B in susceptibility.

    Science.gov (United States)

    Archer, Natalie P; Perez-Andreu, Virginia; Stoltze, Ulrik; Scheurer, Michael E; Wilkinson, Anna V; Lin, Ting-Nien; Qian, Maoxiang; Goodings, Charnise; Swartz, Michael D; Ranjit, Nalini; Rabin, Karen R; Peckham-Gregory, Erin C; Plon, Sharon E; de Alarcon, Pedro A; Zabriskie, Ryan C; Antillon-Klussmann, Federico; Najera, Cesar R; Yang, Jun J; Lupo, Philip J

    2017-01-01

    We conducted an exome-wide association study of childhood acute lymphoblastic leukemia (ALL) among Hispanics to confirm and identify novel variants associated with disease risk in this population. We used a case-parent trio study design; unlike more commonly used case-control studies, this study design is ideal for avoiding issues with population stratification bias among this at-risk ethnic group. Using 710 individuals from 323 Guatemalan and US Hispanic families, two inherited SNPs in ARID5B reached genome-wide level significance: rs10821936, RR = 2.31, 95% CI = 1.70-3.14, p = 1.7×10-8 and rs7089424, RR = 2.22, 95% CI = 1.64-3.01, p = 5.2×10-8. Similar results were observed when restricting our analyses to those with the B-ALL subtype: ARID5B rs10821936 RR = 2.22, 95% CI = 1.63-3.02, p = 9.63×10-8 and ARID5B rs7089424 RR = 2.13, 95% CI = 1.57-2.88, p = 2.81×10-7. Notably, effect sizes observed for rs7089424 and rs10821936 in our study were >20% higher than those reported among non-Hispanic white populations in previous genetic association studies. Our results confirmed the role of ARID5B in childhood ALL susceptibility among Hispanics; however, our assessment did not reveal any strong novel inherited genetic risks for acute lymphoblastic leukemia among this ethnic group.

  19. The 2-min walk test is sufficient for evaluating walking abilities in sporadic inclusion body myositis.

    Science.gov (United States)

    Alfano, L N; Lowes, L P; Dvorchik, I; Yin, H; Maus, E G; Flanigan, K M; Mendell, J R

    2014-03-01

    Sporadic inclusion body myositis causes progressive functional loss due to declining muscle strength. Although the underlying cause is unknown, clinical trials are underway to improve strength and function. Selection of appropriate outcome measures is critical for the success of these trials. The 6-min walk test has been the de facto standard for assessing function in neuromuscular disease; however, the optimal walking test has not been determined in this disease. In this study, 67 individuals with sporadic inclusion body myositis completed a battery of quantitative strength and functional tests including timed walking tests, patient-reported outcomes, and other tasks. The 2-min and 6-min walk tests are highly correlated to each other (r=0.97, pwalk test, but 7% of subjects were unable to walk the full 6-min of the 6-min walk test due to fatigue. The 2-min walk test demonstrates similar correlation to all outcomes compared to the 6-min walk test, is less fatiguing and better tolerated. Results suggest that the 2-min walk test is a better alternative to tests of longer duration. Further research is needed to determine longitudinal changes on this outcome. Copyright © 2013 Elsevier B.V. All rights reserved.

  20. [A rare complication of dysarthria in a patient with inclusion body myositis: a case report].

    Science.gov (United States)

    Isayama, Reina; Shiga, Kensuke; Tanaka, Eijirou; Itsukage, Masahiro; Tokuda, Takahiko; Nakagawa, Masanori

    2010-10-01

    We reported a 71-year-old man with inclusion body myositis with clinically overt dysarthria. He had been suffering from gradual progression of weakness in the hand muscles and lower extremities as well as dysarthria three years before admission. His neurological examination revealed muscle atrophy and weakness in the tongue, the forearm flexors, and the vastus medialis muscles. He had dysarthria to a moderate degree, while he denied any dysphasia. A biopsy from vastus lateralis muscle showed variation in fiber size, infiltration of mononucleated cells, and numerous fibers with rimmed vacuoles, leading to the diagnosis of definite inclusion body myositis. The EMG findings of the tongue demonstrated low amplitude motor unit potentials during voluntary contraction, abundant fibrillation potentials at rest, and preserved interference pattern at maximal contraction, implying myogenic changes. We surmised the dysarthria seen in this patient, an atypical clinical feature in IBM, presumably caused by muscle involvement in the tongue muscle. Dysphasia is common symptom in IBM patient and has been much reported previously. But dysarthria in IBM patient has not been aware, for this reason this report should be the rare case.

  1. Non-infectious myositis of the lateral pterygoid muscle: a report of four cases.

    Science.gov (United States)

    Kang, J-H; Huh, K-H; Kho, H-S

    2015-02-01

    Non-infectious myositis is a condition characterized by chronic localized myalgia originating from central nervous system effects. It is also known as centrally mediated myalgia associated with neurogenic inflammation. When this condition occurs in the lateral pterygoid muscle, clinical evaluation is difficult due to its inaccessible anatomic location. In order to diagnose this rare condition, careful clinical examination and advanced imaging are necessary. The authors report herein four cases of non-infectious myositis of the lateral pterygoid muscle diagnosed by magnetic resonance or enhanced computed tomography imaging. The patients reported prolonged parafunctional habits and chronic jaw pain. In each case, clinical signs suggested the diagnosis of anterior disc displacement without reduction, but the progressive history of internal derangement did not fit this diagnosis. Limited lateral excursion was observed, and patients reported pain in the temporomandibular joint (TMJ) area without tenderness to palpation of the TMJ. Advanced imaging, including axial views, provided valuable information for accurate diagnosis and appropriate management. Copyright © 2014 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

  2. Amyloid deposits and inflammatory infiltrates in sporadic inclusion body myositis: the inflammatory egg comes before the degenerative chicken

    NARCIS (Netherlands)

    Benveniste, O.; Stenzel, W.; Hilton-Jones, D.; Sandri, M.; Boyer, O.; Engelen, B.G.M. van

    2015-01-01

    Sporadic inclusion body myositis (sIBM) is the most frequently acquired myopathy in patients over 50 years of age. It is imperative that neurologists and rheumatologists recognize this disorder which may, through clinical and pathological similarities, mimic other myopathies, especially

  3. Childhood osteomyelitis-incidence and differentiation from other acute onset musculoskeletal features in a population-based study

    Science.gov (United States)

    Riise, Øystein Rolandsen; Kirkhus, Eva; Handeland, Kai Samson; Flatø, Berit; Reiseter, Tor; Cvancarova, Milada; Nakstad, Britt; Wathne, Karl-Olaf

    2008-01-01

    Background Osteomyelitis can be difficult to diagnose and there has previously not been a prospective approach to identify all children in a defined geographic area. The aim of this study was to assess the annual incidence of osteomyelitis in children, describe the patient and disease characteristics in those with acute (osteomyelitis (≥ 14 days disease duration), and differentiate osteomyelitis patients from those with other acute onset musculoskeletal features. Methods In a population-based Norwegian study physicians were asked to refer all children with suspected osteomyelitis. Children with osteomyelitis received follow-up at six weeks, six months and thereafter as long as clinically needed. Results The total annual incidence rate of osteomyelitis was 13 per 100 000 (acute osteomyelitis 8 and subacute osteomyelitis 5 per 100 000). The incidence was higher in patients under the age of 3 than in older children (OR 2.9, 95%: CI 2.3–3.7). The incidence of non-vertebral osteomyelitis was higher than the incidence of vertebral osteomyelitis (10 vs. 3 per 100 000; p = .002). Vertebral osteomyelitis was more frequent in girls than in boys (OR 7.0, 95%: CI 3.3–14.7). ESR ≥ 40 mm/hr had the highest positive predictive laboratory value to identify osteomyelitis patients at 26% and MRI had a positive predictive value of 85%. Long-bone infection was found in 16 (43%) patients. ESR, CRP, white blood cell count, neutrophils and platelet count were higher for patients with acute osteomyelitis than for patients with subacute osteomyelitis. Subacute findings on MRI and doctor's delay were more common in subacute osteomyelitis than in acute osteomyelitis patients. Blood culture was positive in 26% of the acute osteomyelitis patients and was negative in all the subacute osteomyelitis patients. Conclusion The annual incidence of osteomyelitis in Norway remains high. ESR values and MRI scan may help to identify osteomyelitis patients and differentiate acute and subacute

  4. Analysis of factors influencing the overall effect of racecadotril on childhood acute diarrhea. Results from a real-world and post-authorization surveillance study in Venezuela

    Directory of Open Access Journals (Sweden)

    Jose Chacón

    2010-06-01

    Full Text Available Jose ChacónOn behalf of the Racecadotril Post-authorization Record Group; Centro Clinico Profesional Caracas, Caracas, VenezuelaAbstract: Drug efficacy might differ from clinical trial results when performed in clinical daily conditions. Therefore, it is mandatory to conduct trials about effectiveness to improve external validity. This post-authorization, open-label, noncontrolled, prospective, multicenter, observational, and naturalistic trial was designed to search for factors influencing the racecadotril overall effect on childhood acute watery diarrhea in a real-world setting of Venezuela. There were 3,873 children with acute watery diarrhea treated with racecadotril, an enkephalin breakdown blocker plus oral rehydration therapy by 97 pediatricians. Evaluations were carried out daily until emission of two consecutive formed stools or absence of watery bowel movements for 24 hours. The primary end-point was time-to-relief, defined as the time from first racecadotril dose to the last watery bowel movement time. Age, gender, nursing type, nursing status during diarrhea, diarrhea severity, and co-medication were considered as factors in the statistical analysis. The primary end-point was evaluated by factors using UNIANOVA, and post-hoc tests were done. A multiple regression analysis was carried out to identify factors affecting drug performance, racecadotril effectiveness and tolerability overall assessment was searched by physicians and patients, and inter-observer agreement was evaluated by kappa statistics. The mean time-to-relief was 18.5 ± 12.5 hours [95% confidence interval 17.9–19.0] and the diarrhea severity was the only variable with significant and independent weight on racecadotril effectiveness explaining 23% of time-to-relief variance, but even in severe diarrhea cases this time was less than 24 hours. High agreement about satisfactory perception on effectiveness and tolerability was reached among physicians and patients. In

  5. Childhood osteomyelitis-incidence and differentiation from other acute onset musculoskeletal features in a population-based study

    Directory of Open Access Journals (Sweden)

    Reiseter Tor

    2008-10-01

    Full Text Available Abstract Background Osteomyelitis can be difficult to diagnose and there has previously not been a prospective approach to identify all children in a defined geographic area. The aim of this study was to assess the annual incidence of osteomyelitis in children, describe the patient and disease characteristics in those with acute ( Methods In a population-based Norwegian study physicians were asked to refer all children with suspected osteomyelitis. Children with osteomyelitis received follow-up at six weeks, six months and thereafter as long as clinically needed. Results The total annual incidence rate of osteomyelitis was 13 per 100 000 (acute osteomyelitis 8 and subacute osteomyelitis 5 per 100 000. The incidence was higher in patients under the age of 3 than in older children (OR 2.9, 95%: CI 2.3–3.7. The incidence of non-vertebral osteomyelitis was higher than the incidence of vertebral osteomyelitis (10 vs. 3 per 100 000; p = .002. Vertebral osteomyelitis was more frequent in girls than in boys (OR 7.0, 95%: CI 3.3–14.7. ESR ≥ 40 mm/hr had the highest positive predictive laboratory value to identify osteomyelitis patients at 26% and MRI had a positive predictive value of 85%. Long-bone infection was found in 16 (43% patients. ESR, CRP, white blood cell count, neutrophils and platelet count were higher for patients with acute osteomyelitis than for patients with subacute osteomyelitis. Subacute findings on MRI and doctor's delay were more common in subacute osteomyelitis than in acute osteomyelitis patients. Blood culture was positive in 26% of the acute osteomyelitis patients and was negative in all the subacute osteomyelitis patients. Conclusion The annual incidence of osteomyelitis in Norway remains high. ESR values and MRI scan may help to identify osteomyelitis patients and differentiate acute and subacute osteomyelitis.

  6. White versus gray matter function as seen on neuropsychological testing following bone marrow transplant for acute leukemia in childhood

    Directory of Open Access Journals (Sweden)

    Fiona S Anderson

    2008-03-01

    Full Text Available Fiona S Anderson1, Alicia S Kunin-Batson1, Joanna L Perkins2, K Scott Baker31Divisions of Pediatric Clinical Neuroscience; 2Department of Pediatric Hematology/Oncology, Children’s Hospitals and Clinics, Minneapolis, MN, USA and 3Hematology/Oncology/BMT, Department of Pediatrics, University of Minnesota, Minneapolis, MN, USAAbstract: Current theory suggests that neurocognitive late effects of treatments for childhood cancer such as difficulties with attention, processing speed and visual-motor ability are the result of white matter damage. Neuroimaging studies have produced a variety of white matter findings. However, although white matter is thought to be differentially affected, previous studies have not demonstrated a discrepancy between white and gray matter function. The present study included 36 children treated for childhood leukemia with hematopoietic stem cell transplant (HCT. Their performance on neurocognitive measures traditionally thought to measure white matter was compared to performance on measures thought to measure gray matter function. Composite white and gray matter standard scores were created based on neuropsychological measures that individuals with known white or gray matter damage perform poorly. As predicted, composite white matter scores (mean = 98.1 were significantly lower (t = 2.26, p = 0.03 than composite gray matter scores (mean = 102.5. Additionally, as gray matter performance increased, the difference between gray and white matter scores increased (R = 0.353, p = 0.035. Overall, the results of this study support the current theory that white matter damage is responsible for the more subtle neurocognitive late effects resulting from treatment for childhood leukemia.Keywords: late effects of cancer treatment, leukemia, neuropsychology, white matter, brain function

  7. Effects of Methylphenidate on Attention Deficits in Childhood Cancer Survivors

    Science.gov (United States)

    2015-03-16

    ALL, Childhood; Leukemia, Lymphoblastic; Leukemia, Lymphoblastic, Acute; Leukemia, Lymphoblastic, Acute, L1; Leukemia, Lymphoblastic, Acute, L2; Leukemia, Lymphoblastic, Acute, Philadelphia-Positive; Leukemia, Lymphocytic, Acute; Leukemia, Lymphocytic, Acute, L1; Leukemia, Lymphocytic, Acute, L2; Lymphoblastic Leukemia; Lymphoblastic Leukemia, Acute; Lymphoblastic Leukemia, Acute, Childhood; Lymphoblastic Leukemia, Acute, L1; Lymphoblastic Leukemia, Acute, L2; Lymphoblastic Lymphoma; Lymphocytic Leukemia, Acute; Lymphocytic Leukemia, L1; Lymphocytic Leukemia, L2; Brain Tumors; Cancer of the Brain; Cancer of Brain; Malignant Primary Brain Tumors; Brain Neoplasms, Malignant

  8. Tretinoin, Cytarabine, and Daunorubicin Hydrochloride With or Without Arsenic Trioxide Followed by Tretinoin With or Without Mercaptopurine and Methotrexate in Treating Patients With Acute Promyelocytic Leukemia

    Science.gov (United States)

    2013-06-04

    Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Promyelocytic Leukemia (M3); Childhood Acute Promyelocytic Leukemia (M3); Untreated Adult Acute Myeloid Leukemia; Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

  9. High-risk childhood acute lymphoblastic leukemia in first remission treated with novel intensive chemotherapy and allogeneic transplantation.

    NARCIS (Netherlands)

    Marshall, G.M.; Pozza, L. Dalla; Sutton, R.; Ng, A.; Groot-Kruseman, H.A. de; Velden, V.H. van der; Venn, N.C.; Berg, H. van den; Bont, E.S. de; rten Egeler, R. Maa; Hoogerbrugge, P.M.; Kaspers, G.J.L.; Bierings, M.B.; Schoot, E. van der; Dongen, J. Van; Law, T.; Cross, S.; Mueller, H.; Haas, V. de; Haber, M.; Revesz, T.; Alvaro, F.; Suppiah, R.; Norris, M.D.; Pieters, R.

    2013-01-01

    Children with acute lymphoblastic leukemia (ALL) and high minimal residual disease (MRD) levels after initial chemotherapy have a poor clinical outcome. In this prospective, single arm, Phase 2 trial, 111 Dutch and Australian children aged 1-18 years with newly diagnosed, t(9;22)-negative ALL, were

  10. Long-term results of NOPHO ALL-92 and ALL-2000 studies of childhood acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Schmiegelow, K; Forestier, E; Hellebostad, M

    2010-01-01

    Analysis of 2668 children with acute lymphoblastic leukemia (ALL) treated in two successive Nordic clinical trials (Nordic Society of Paediatric Haematology and Oncology (NOPHO) ALL-92 and ALL-2000) showed that 75% of all patients are cured by first-line therapy, and 83% are long-term survivors...

  11. Favorable outcome after 1-year treatment of childhood T-cell lymphoma/T-cell acute lymphoblastic leukemia

    NARCIS (Netherlands)

    van den Berg, H.; Zsiros, J.; Veneberg, A.; Schutten, N. J.; Kroes, W.; Slater, R. M.; Behrendt, H.

    1998-01-01

    For T-malignancies in children a poor prognosis is reported. In these malignancies a combination of lymphoma and leukemia is commonly seen at presentation and most patients are treated according to protocols for acute lymphoblastic leukemia (ALL). These protocols are often designed for the majority

  12. Treatment effect and safety of EPs 7630-solution in acute bronchitis in childhood: report of a multicentre observational study.

    Science.gov (United States)

    Haidvogl, M; Heger, M

    2007-01-01

    An open post-marketing surveillance study was conducted to examine the treatment effect and safety of EPs 7630-solution in the treatment of acute bronchitis in children. This study included a total of 742 children (aged between 0 and 12 years) with acute bronchitis (83.4%) or acute exacerbations of chronic bronchitis (14.3%), who were treated with different doses of the herbal drug for up to 14 days. Five bronchitis specific symptoms (BSS) were summed up to give an overall measure of disease severity. Non-specific disease symptoms (loss of appetite, diarrhoea, headache, vomiting, and fever) were also recorded, together with adverse events and overall ratings of efficacy and tolerability. The overall BSS score decreased during treatment from 6.0+/-3.0 points at baseline to 2.7+/-2.5 points after 7 days and to 1.4+/-2.1 points after 14 days. Remission or improvement in at least 80% of patients was recorded for all the individual component symptoms. The proportion of patients suffering from non-specific symptoms also substantially improved during treatment. For example, loss of appetite was present in 65.8% of patients at study begin, but only in 27.6% at the time point of last observation visit. In 88.3% of cases, the responsible physician rated the treatment as successful. Adverse events were minor and transitory. In conclusion, EPs 7630-solution was shown to be a safe and an effective treatment option for acute bronchitis or acute exacerbations of chronic bronchitis in children.

  13. Association of inclusion body myositis with T cell large granular lymphocytic leukaemia

    DEFF Research Database (Denmark)

    Greenberg, Steven A; Pinkus, Jack L; Amato, Anthony A

    2016-01-01

    on follow-up testing in 15 patients a median of 350 days later. T cell aberrant loss of CD5 or gain of expression of CD16 and CD94 were common (19/42, 45%). In comparison, 2/15 (14%) age-matched patients with dermatomyositis, polymyositis, or necrotizing myopathy, and 0/20 (0%) age-matched healthy subjects...... had large granular lymphocyte expansions, with none of these patients having T cell aberrant expression of CD5, CD16 or CD94. Reduced blood CD4/CD8 ratio, increased blood CD8 count, and lymphocytosis were additional biomarkers highly correlated with flow cytometry-measured large granular lymphocyte...... expansions. Cross-sectional data suggested more aggressive disease in patients with such expansions than without. Muscle immunohistochemistry demonstrated invasion of large granular lymphocytes into muscle in 15/15 inclusion body myositis patients but in only 1/28 patients with dermatomyositis...

  14. Intercostal myositis ossificans misdiagnosed as osteosarcoma in a 10-year-old child

    Energy Technology Data Exchange (ETDEWEB)

    Koob, Meriam; Durckel, Jean; Dosch, Jean-Claude; Dietemann, Jean-Louis [Hopital de Hautepierre, Service de Radiologie II, Hopitaux Universitaires, Strasbourg Cedex (France); Entz-Werle, Natacha [Hopitaux Universitaires, Hopital de Hautepierre, Service d' Onco-hematologie pediatrique, Strasbourg Cedex (France)

    2010-12-15

    Myositis ossificans (MO) is a rare benign cause of heterotopic bone formation within soft tissue. It most commonly affects adolescents and young adults, typically in the limbs and following trauma. Very few cases have been reported in children. We report here a case of nontraumatic MO occurring in a 10-year-old girl with an uncommon location in the 5th right intercostal space; it was initially misdiagnosed and treated as osteosarcoma. Imaging findings including plain radiographs, CT, MRI, bone scintigraphy and PET-CT are described. This case highlights the central role played by imaging in diagnosis, thus avoiding biopsy that can erroneously suggest osteosarcoma as the diagnosis, as occurred in this case. (orig.)

  15. A dysphagia study in patients with sporadic inclusion body myositis (s-IBM).

    Science.gov (United States)

    Murata, Ken-Ya; Kouda, Ken; Tajima, Fumihiro; Kondo, Tomoyoshi

    2012-08-01

    The nature of the swallowing impairment in patients with sporadic inclusion body myositis (s-IBM) has not been well characterized. In this study, we examined ten consecutive s-IBM patients using videofluoroscopy (VF) and computed pharyngoesophageal manometry (CPM). The patients were divided into two groups: patients with complaint and without complaint of dysphagia. VF results indicated pharyngeal muscle propulsion (PP) at the hypopharyngeal and upper esophagus sphincter (UES) in all s-IBM patients. Patients without complaint of dysphagia showed a mild degree of PP, whereas a severe form of PP was observed in patients with complaint of dysphagia. CPM revealed that negative pressure during UES opening was not observed in the s-IBM patients with complaint of dysphagia. Incomplete opening and PP at the UES were observed in all s-IBM patients. These results indicate that the dysphagic processes occur subclinically in s-IBM patients who may not report swallowing impairments.

  16. Eosinophilic myositis resulted from Sarcocystis infection in prime marbled beef of Japanese black cattle

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    Tohru Kimura

    Full Text Available Partial changes of color (greenish to brownish were found in prime marbled beef of Japanese black cattle. The disseminated lesions of the skeletal muscles were histopathologically examined in relation to Sarcocystis infection. The lesions in the muscles showed granulomas with inflammatory cell infiltration. The sarcocysts had a distinct wall, which was radically striated by palisading villar protrusions. The sarcocyst wall was surrounded by degenerative eosinophils and necrotic muscle fibers. In conclusion, eosinophilic myositis in prime marbled beef of Japanese black cattle resulted from Sarcocystis spp. infection. The muscular lesions were characterized by the presence of granulomas and capsulated sarcocysts surrounded by numerous eosinophils. [Vet. World 2011; 4(11.000: 500-502

  17. Significant male preponderance in childhood acute lymphoblastic leukemia in India and regional variation: tertiary care center experience, systematic review, and evaluation of population-based data.

    Science.gov (United States)

    Kulkarni, Ketan Prasad; Marwaha, Ram Kumar

    2013-09-01

    Although, a slight male preponderance has been reported in childhood acute lymphoblastic leukemia (ALL) from several developed nations, several Indian studies suggest a skewed gender ratio in ALL. To assess the gender ratio at presentation in ALL in India, we used a three-prong approach: (i) center audit, (ii) systematic review of published studies on ALL in India, and (iii) assessment of population based registry data. Data on gender at presentation in ALL were extracted from these multiple sources. In our center audit, we observed a significantly higher of male:female (M:F) ratio of 3.16:1 (P = .046) in ALL as compared to world literature. In the systematic review of all ALL studies from India, 367 articles were identified and reviewed. A total of 4230 and 1843 boys and girls in these studies were assessed and the M:F ratio was 2.503:1; much higher than the world ratio but not significantly different (P = .10). Population-based data obtained from the National Cancer Registry Program also depicted a male preponderance, especially from large cities in India in a consistent manner since 1984. There is also significant (P = .025) interregional variation in the gender ratio in India. Our study clearly demonstrates a consistent male preponderance in childhood ALL in India along with significant interregional variations over the last three decades. There is a clear need of prospective nationwide multicenter assessment of high-resolution data to confirm this important observation and assess its implications, especially on the health care system.

  18. Minimal residual disease-based risk stratification in Chinese childhood acute lymphoblastic leukemia by flow cytometry and plasma DNA quantitative polymerase chain reaction.

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    Suk Hang Cheng

    Full Text Available Minimal residual disease, or MRD, is an important prognostic indicator in childhood acute lymphoblastic leukemia. In ALL-IC-BFM 2002 study, we employed a standardized method of flow cytometry MRD monitoring for multiple centers internationally using uniformed gating, and determined the relevant MRD-based risk stratification strategies in our local patient cohort. We also evaluated a novel method of PCR MRD quantitation using peripheral blood plasma. For the bone marrow flow MRD study, patients could be stratified into 3 risk groups according to MRD level using a single time-point at day-15 (Model I (I-A: 10%, or using two time-points at day-15 and day-33 (Model II (II-A: day-15<10% and day-33<0.01%, II-B: day-15 ≥ 10% or day-33 ≥ 0.01% but not both, II-C: day-15 ≥ 10% and day-33 ≥ 0.01%, which showed significantly superior prediction of relapse (p = .00047 and <0.0001 respectively. Importantly, patients with good outcome (frequency: 56.0%, event-free survival: 90.1% could be more accurately predicted by Model II. In peripheral blood plasma PCR MRD investigation, patients with day-15-MRD ≥ 10(-4 were at a significantly higher risk of relapse (p = 0.0117. By multivariate analysis, MRD results from both methods could independently predict patients' prognosis, with 20-35-fold increase in risk of relapse for flow MRD I-C and II-C respectively, and 5.8-fold for patients having plasma MRD of ≥ 10(-4. We confirmed that MRD detection by flow cytometry is useful for prognostic evaluation in our Chinese cohort of childhood ALL after treatment. Moreover, peripheral blood plasma DNA MRD can be an alternative where bone marrow specimen is unavailable and as a less invasive method, which allows close monitoring.

  19. Quality of health in survivors of childhood acute myeloid leukemia treated with chemotherapy only: A NOPHO-AML study

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    Molgaard-Hansen, Lene; Glosli, Heidi; Jahnukainen, Kirsi

    2011-01-01

    More than 60% of children with acute myeloid leukemia (AML) become long-term survivors, and approximately 50% are cured with chemotherapy only. Limited data exist about their long-term morbidity and social outcomes. The aim of the study was to compare the self-reported use of health care services......, health experience, social outcomes, and lifestyle behavior of AML survivors with that of their sibling controls....

  20. Prognostic significance of bi/oligoclonality in childhood acute lymphoblastic leukemia as determined by polymerase chain reaction

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    Carlos Alberto Scrideli

    2001-09-01

    Full Text Available CONTEXT: The CDR-3 region of heavy-chain immunoglobulin has been used as a clonal marker in the study of minimal residual disease in children with acute lymphoblastic leukemia. Southern blot and polymerase chain reaction studies have demonstrated the occurrence of bi/oligoclonality in a variable number of cases of B-lineage acute lymphoblastic leukemia, a fact that may strongly interfere with the detection of minimal residual disease. Oligoclonality has also been associated with a poorer prognosis and a higher chance of relapse. OBJECTIVES: To correlate bi/oligoclonality, detected by polymerase chain reaction in Brazilian children with B-lineage acute lymphoblastic leukemia with a chance of relapse, with immunophenotype, risk group, and disease-free survival. DESIGN: Prospective study of patients’ outcome. SETTING: Pediatric Oncology Unit of the University Hospital, Faculty of Medicine of Ribeirão Preto, University of São Paulo. PARTICIPANTS: 47 children with acute lymphoblastic leukemia DIAGNOSTIC TEST: Polymerase chain reaction using consensus primers for the CDR-3 region of heavy chain immunoglobulin (FR3A, LJH and VLJH for the detection of clonality. RESULTS: Bi/oligoclonality was detected in 15 patients (31.9%. There was no significant difference between the groups with monoclonality and biclonality in terms of the occurrence of a relapse (28.1% versus 26.1%, presence of CALLA+ (81.2% versus 80% or risk group (62.5% versus 60%. Disease-free survival was similar in both groups, with no significant difference (p: 0.7695. CONCLUSIONS: We conclude that bi/oligoclonality was not associated with the factors investigated in the present study and that its detection in 31.9% of the patients may be important for the study and monitoring of minimal residual disease.

  1. Efficacy of traditional rice-lentil-yogurt diet, lactose free milk protein-based formula and soy protein formula in management of secondary lactose intolerance with acute childhood diarrhoea.

    Science.gov (United States)

    Nizami, S Q; Bhutta, Z A; Molla, A M

    1996-06-01

    Secondary lactose intolerance is often a cause of prolongation of diarrhoeal episodes. As appropriate management of lactose intolerance is elimination of lactose from diet, expansive lactose free formulae are often prescribed in acute childhood diarrhoea without establishing diagnosis of lactose intolerance. Since cheap weaning diets made from locally available cereals have been found effective in management of persistent diarrhoea, we postulated that same weaning diet made of rice lentil and yogurt (K-Y diet) could be effectively used in management of acute childhood diarrhoea associated with secondary lactose intolerance. We compared this K-Y diet with milk protein-based lactose free and soy-protein formula. Thirty children between 3-18 months of age completed dietary trial for 72 h. Of these nine children received K-Y diet (Group A), four children received milk protein-based formula (Group B) and 11 children received soy protein formula (Group C). Stool frequency was significantly reduced in children in Group A (13 +/- 6 on day 1 to 6 +/- 5 on day 3) and in Group B (13 +/- 5 on day 1 to 7 +/- 4 on day 3), but not in Group C (13 +/- 4 on day 1 to 10 +/- 8 on day 3). No significant difference was observed in intake of diet, total calories intake, and fluid intake among the three groups. It is concluded that cheap weaning diet made of locally available cereals and yogurt can be used effectively in management of secondary lactose intolerance associated with acute childhood diarrhoea.

  2. Absolute Lymphocyte Count Recovery Independently Predicts Outcome in Childhood Acute Lymphoblastic Leukemia: Experience From a Tertiary Care Cancer Center of a Developing Country.

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    Gupta, Anshul; Kapoor, Gauri; Jain, Sandeep; Bajpai, Ram

    2015-04-01

    Accurate risk stratification is essential for successful treatment outcome in childhood acute lymphoblastic leukemia. Early recovery of absolute lymphocyte count (ALC) during induction therapy is emerging as a reliable favorable prognostic indicator that may hold its relevance in resource-constraint settings. This is a retrospective chart review of medical records of 212 patients of acute lymphoblastic leukemia, aged less than 18 years, treated between January 1996 and December 2009. Time to lymphocyte recovery was analyzed with respect to various prognostic factors and survival and Martingale residuals were used to define ALC cut-offs. High-risk disease characteristics including older age (10 y and older), National Cancer Institute high risk, and central nervous system disease at diagnosis were associated with delayed lymphocyte recovery. The 5-year event-free, relapse-free, and overall survival of patients with day 15 ALC of ≥ 500 cells/µL and day 29 ALC of ≥ 1000 cells/µL was 81.7% ± 4%, 86.4% ± 2.8%, 91.0% ± 3%, respectively, compared with those with delayed recovery (16.6% ± 5.6%, 19.3% ± 6.4%, 32.8% ± 7.2%, P < 0.001). In multivariate analysis both these ALC cut-offs retained their significance as prognostic variables of survival. Our analysis revealed ALC to be an important independent predictor of treatment outcome and may provide key prognostic information in settings where minimal residual disease-based risk stratification is not feasible.

  3. Analysis of factors influencing the overall effect of racecadotril on childhood acute diarrhea. Results from a real-world and post-authorization surveillance study in Venezuela.

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    Chacón, Jose

    2010-07-21

    Drug efficacy might differ from clinical trial results when performed in clinical daily conditions. Therefore, it is mandatory to conduct trials about effectiveness to improve external validity. This post-authorization, open-label, noncontrolled, prospective, multicenter, observational, and naturalistic trial was designed to search for factors influencing the racecadotril overall effect on childhood acute watery diarrhea in a real-world setting of Venezuela. There were 3,873 children with acute watery diarrhea treated with racecadotril, an enkephalin breakdown blocker plus oral rehydration therapy by 97 pediatricians. Evaluations were carried out daily until emission of two consecutive formed stools or absence of watery bowel movements for 24 hours. The primary end-point was time-to-relief, defined as the time from first racecadotril dose to the last watery bowel movement time. Age, gender, nursing type, nursing status during diarrhea, diarrhea severity, and co-medication were considered as factors in the statistical analysis. The primary end-point was evaluated by factors using UNIANOVA, and post-hoc tests were done. A multiple regression analysis was carried out to identify factors affecting drug performance, racecadotril effectiveness and tolerability overall assessment was searched by physicians and patients, and inter-observer agreement was evaluated by kappa statistics. The mean time-to-relief was 18.5 +/- 12.5 hours [95% confidence interval 17.9-19.0] and the diarrhea severity was the only variable with significant and independent weight on racecadotril effectiveness explaining 23% of time-to-relief variance, but even in severe diarrhea cases this time was less than 24 hours. High agreement about satisfactory perception on effectiveness and tolerability was reached among physicians and patients. In conclusion, the racecadotril overall effect, evaluated in a real-world setting of Venezuela, was in agreement with results of some earlier controlled trials. It

  4. Sex disparity in childhood and young adult acute myeloid leukemia (AML) survival: Evidence from US population data.

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    Hossain, Md Jobayer; Xie, Li

    2015-12-01

    Sex variation has been persistently investigated in studies concerning acute myeloid leukemia (AML) survival outcomes but has not been fully explored among pediatric and young adult AML patients. We detected sex difference in the survival of AML patients diagnosed at ages 0-24 years and explored distinct effects of sex across subgroups of age at diagnosis, race-ethnicity and AML subtypes utilizing the United States Surveillance Epidemiology and End Results (SEER) population based dataset of 4865 patients diagnosed with AML between 1973 and 2012. Kaplan-Meier survival function, propensity scores and stratified Cox proportional hazards regression were used for data analyses. After controlling for other prognostic factors, females showed a significant survival advantage over their male counterparts, adjusted hazard ratio (aHR, 95% confidence interval (CI): 1.09, 1.00-1.18). Compared to females, male patients had substantially increased risk of mortality in the following subgroups of: ages 20-24 years at diagnosis (aHR1.30), Caucasian (1.14), acute promyelocytic leukemia (APL) (1.35), acute erythroid leukemia (AEL) (1.39), AML with inv(16)(p13.1q22) (2.57), AML with minimum differentiation (1.47); and had substantially decreased aHR in AML t(9;11)(p22;q23) (0.57) and AML with maturation (0.82). Overall, females demonstrated increased survival over males and this disparity was considerably large in patients ages 20-24 years at diagnosis, Caucasians, and in AML subtypes of AML inv(16), APL and AEL. In contrast, males with AML t(9;11)(p22;q23), AML with maturation and age at diagnosis of 10-14 years showed survival benefit. Further investigations are needed to detect the biological processes influencing the mechanisms of these interactions. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Medial rectus muscle myositis as an atypical presentation of mucosa-associated lymphatic tissue lymphoma: a case report

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    Juliana Sá Freire Medrado Dias

    2014-04-01

    Full Text Available Here we describe the rare case of a 55-year-old man with medial rectus muscle myositis as an atypical presentation of non-Hodgkin B-cell mucosa-associated lymphoma (MALT. Pathology and immunohistochemistry of the affected muscle confirmed the diagnosis of a neoplasm. The primary etiology of orbital myositis is Graves' ophthalmopathy, but several other diseases may cause this clinical presentation. Therefore, the neoplastic causes must be eliminated from the differential diagnoses. non-Hodgkin B-cell mucosa-associated lymphoma is the most common histological type of lymphoma in the orbit, with the conjunctiva and lacrimal glands being the most commonly affected sites. However, it may also present in atypical forms involving others sites and tissues.

  6. Childhood acute basilar artery thrombosis successfully treated with mechanical thrombectomy using stent retrievers: case report and review of the literature.

    Science.gov (United States)

    Nicosia, Giancarlo; Cicala, Domenico; Mirone, Giuseppe; Spennato, Pietro; Trischitta, Vincenzo; Ruggiero, Claudio; Guarneri, Gianluigi; Muto, Mario; Cinalli, Giuseppe

    2017-02-01

    Acute basilar artery occlusion (ABAO) is an infrequent but potentially fatal cause of strokes in both adults and children, and it is usually due to vertebral artery dissection (VAD). VAD has been found to be usually a consequence of traumatic vertebral artery injury. ABAO usually presents with symptoms of acute ischemic stroke (AIS) of the posterior circulation or transient ischemic attack (TIA). It may lead to death or long-term disability if not promptly recanalized. Basilar artery recanalization in children can be achieved safely and with excellent clinical outcome using endovascular thrombectomy with the new generation self-expanding and retrievable stents. We report the case of a 23-month old baby that came to the emergency room of our hospital for progressive impairment of consciousness associated with widespread stiffness and plaintive cry, appeared after accidental fall from stroller. An emergency brain CT scan was obtained showing multiple infarction lesions in the brainstem and left cerebellum suggestive of acute stroke in posterior circulation territories. An MR scan with angiography and diffusion-weighted sequences confirmed the multiple infarction lesions and demonstrated poor representation of the flow signal at the V3 segment of the left vertebral artery and absent representation of the flow signal at the distal segment of the basilar artery suggestive of acute thrombotic occlusion. The patient was immediately referred to interventional neuroradiology unit, and digital subtraction angiography showed complete basilar artery occlusion and left vertebral artery dissection at extracranial V2-V3 segment. The patient underwent intra-arterial thrombectomy using stent retrievers and occlusion of the V2-V3 segment of the left vertebral artery. The patient survived and long-term outcome was excellent. To our knowledge, only nine cases of ABAO in children treated with intra-arterial thrombectomy have been previously reported in the literature. In only three

  7. Caspofungin Acetate or Fluconazole in Preventing Invasive Fungal Infections in Patients With Acute Myeloid Leukemia Who Are Undergoing Chemotherapy

    Science.gov (United States)

    2017-01-31

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Childhood Acute Erythroleukemia (M6); Childhood Acute Megakaryocytic Leukemia (M7); Childhood Acute Minimally Differentiated Myeloid Leukemia (M0); Childhood Acute Monoblastic Leukemia (M5a); Childhood Acute Monocytic Leukemia (M5b); Childhood Acute Myeloblastic Leukemia With Maturation (M2); Childhood Acute Myeloblastic Leukemia Without Maturation (M1); Childhood Acute Myeloid Leukemia in Remission; Childhood Acute Myelomonocytic Leukemia (M4); Fungal Infection; Neutropenia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia; Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

  8. Relapse of childhood acute lymphoblastic leukemia and outcomes at a reference center in Latin America: organomegaly at diagnosis is a significant clinical predictor.

    Science.gov (United States)

    Jaime-Pérez, José Carlos; Pinzón-Uresti, Mónica Andrea; Jiménez-Castillo, Raúl Alberto; Colunga-Pedraza, Julia Esther; González-Llano, Óscar; Gómez-Almaguer, David

    2018-01-01

    Relapse is the major cause of treatment failure in acute lymphoblastic leukemia (ALL) of childhood; it is more frequent among high-risk patients from low-middle income than from high-income countries. The frequency, sites and outcome of relapsed ALL in children of northeast Mexico over a decade was documented. A retrospective analysis of 246 children belonging to a low-income group death were estimated by the Cox regression model. Very early relapse was defined as that occurring in 36 months from diagnosis, respectively. Eighty-seven (35.4%) children relapsed. Five-year OS was 82.6% in children without relapse vs. 42% for relapsed patients. Bone marrow (BM) was the most frequent site of relapse (51.72%). Isolated central nervous system (CNS) relapses occurred in 29.9%. Five-year OS was 11.2% for BM and 15.5% for early relapse. HR of relapse for organomegaly was 3.683, 2.247 for an initial white blood cell count >50 000 × 10 9 /l and 1.169 for positive minimal residual disease status. A high rate of very early, CNS, and BM relapse with a considerably low 5-year OS requiring reassessment of therapy was documented. Organomegaly at diagnosis was a highly significant clinical predictor for relapse.

  9. The impact of therapy for childhood acute lymphoblastic leukaemia on intelligence quotients; results of the risk-stratified randomized central nervous system treatment trial MRC UKALL XI

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    Vargha-Khadem Faraneh

    2011-10-01

    Full Text Available Abstract Background The MRC UKALLXI trial tested the efficacy of different central nervous system (CNS directed therapies in childhood acute lymphoblastic leukaemia (ALL. To evaluate morbidity 555/1826 randomised children underwent prospective psychological evaluations. Full Scale, verbal and performance IQs were measured at 5 months, 3 years and 5 years. Scores were compared in; (1 all patients (n = 555 versus related controls (n = 311, (2 low-risk children (presenting white cell count (WCC 9/l randomised to intrathecal methotrexate (n = 197 versus intrathecal and high-dose intravenous methotrexate (HDM (n = 202, and (3 high-risk children (WCC ≥ 50 × 109/l, age ≥ 2 years randomised to HDM (n = 79 versus cranial irradiation (n = 77. Results There were no significant differences in IQ scores between the treatment arms in either low- or high-risk groups. Despite similar scores at baseline, results at 3 and 5 years showed a significant reduction of between 3.6 and 7.3 points in all three IQ scores in all patient groups compared to controls (P Conclusion Children with ALL are at risk of CNS morbidity, regardless of the mode of CNS-directed therapy. Further work needs to identify individuals at high-risk of adverse CNS outcomes. Trial registration ISRCTN: ISRCTN16757172

  10. Living near overhead high voltage transmission power lines as a risk factor for childhood acute lymphoblastic leukemia: a case-control study.

    Science.gov (United States)

    Sohrabi, Mohammad-Reza; Tarjoman, Termeh; Abadi, Alireza; Yavari, Parvin

    2010-01-01

    This study aimed to investigate association of living near high voltage power lines with occurrence of childhood acute lymphoblastic leukemia (ALL). Through a case-control study 300 children aged 1-18 years with confirmed ALL were selected from all referral teaching centers for cancer. They interviewed for history of living near overhead high voltage power lines during at least past two years and compared with 300 controls which were individually matched for sex and approximate age. Logistic regression, chi square and paired t-tests were used for analysis when appropriate. The case group were living significantly closer to power lines (Plines (Plines against more than 600 meters. This ratio estimated as 9.93 (95%CI: 3.47 to 28.5) for 123 KV, 10.78 (95%CI: 3.75 to 31) for 230 KV and 2.98 (95%CI: 0.93 to 9.54) for 400 KV lines. Odds of ALL decreased 0.61 for every 600 meters from the nearest power line. This study emphasizes that living close to high voltage power lines is a risk for ALL.

  11. Baicalein Triggers Mitochondria-Mediated Apoptosis and Enhances the Antileukemic Effect of Vincristine in Childhood Acute Lymphoblastic Leukemia CCRF-CEM Cells

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    Yun-Ju Chen

    2013-01-01

    Full Text Available Acute lymphoblastic leukemia (ALL accounts for approximately 75% of childhood leukemia, and chemotherapy remains the mainstay therapy. Baicalein is an active flavonoid used in traditional Chinese medicine and has recently been found to have anticancer, anti-inflammatory, and antiallergic properties. This study aims to investigate the molecular apoptotic mechanisms of baicalein in CCRF-CEM leukemic cells and to evaluate the combined therapeutic efficacy of baicalein with several commonly used chemotherapeutic drugs in CCRF-CEM cells. Our results demonstrate that baicalein induces mitochondria-dependent cleavage of caspases-9 and -3 and PARP with concomitant decreases in IAP family proteins, survivin, and XIAP. Furthermore, our results present for the first time that baicalein triggers a convergence of the intrinsic and extrinsic apoptotic pathways via the death receptor-caspase 8-tBid signaling cascade in CCRF-CEM cells. In addition, we also present for the first time that the combination of baicalein and vincristine results in a synergistic therapeutic efficacy. Overall, this combination strategy is recommended for future clinical trials in the treatment of pediatric leukemia owing to baicalein’s beneficial effects in alleviating the vomiting, nausea, and skin rashes caused by chemotherapy.

  12. Lymphoid Progenitor Cells from Childhood Acute Lymphoblastic Leukemia Are Functionally Deficient and Express High Levels of the Transcriptional Repressor Gfi-1

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    Jessica Purizaca

    2013-01-01

    Full Text Available Acute lymphoblastic leukemia (ALL is the most frequent malignancy of childhood. Substantial progress on understanding the cell hierarchy within ALL bone marrow (BM has been recorded in the last few years, suggesting that both primitive cell fractions and committed lymphoid blasts with immature stem cell-like properties contain leukemia-initiating cells. Nevertheless, the biology of the early progenitors that initiate the lymphoid program remains elusive. The aim of the present study was to investigate the ability of lymphoid progenitors from B-cell precursor ALL BM to proliferate and undergo multilineage differentiation. By phenotype analyses, in vitro proliferation assays, and controlled culture systems, the lymphoid differentiation potentials were evaluated in BM primitive populations from B-cell precursor ALL pediatric patients. When compared to their normal counterparts, functional stem and progenitor cell contents were substantially reduced in ALL BM. Moreover, neither B nor NK or dendritic lymphoid-cell populations developed recurrently from highly purified ALL-lymphoid progenitors, and their proliferation and cell cycle status revealed limited proliferative capacity. Interestingly, a number of quiescence-associated transcription factors were elevated, including the transcriptional repressor Gfi-1, which was highly expressed in primitive CD34+ cells. Together, our findings reveal major functional defects in the primitive hematopoietic component of ALL BM. A possible contribution of high levels of Gfi-1 expression in the regulation of the stem/progenitor cell biology is suggested.

  13. Assessment of corticosteroid-induced osteonecrosis in children undergoing chemotherapy for acute lymphoblastic leukemia: a report from the Japanese Childhood Cancer and Leukemia Study Group.

    Science.gov (United States)

    Hyakuna, Nobuyuki; Shimomura, Yasuto; Watanabe, Arata; Taga, Takashi; Kikuta, Atsushi; Matsushita, Takeji; Kogawa, Kazuhiro; Kawakami, Chihiro; Horikoshi, Yasuo; Iwai, Tsuyako; Okamoto, Yasuhiro; Tsurusawa, Masahito; Asami, Keiko

    2014-01-01

    Steroid-induced osteonecrosis (ON) is a challenging complication encountered during modern chemotherapy for childhood acute lymphoblastic leukemia (ALL). We retrospectively assessed the incidence of ON and its risk factors in a total of 1095 patients enrolled in 3 consecutive Japanese Children's Cancer and Leukemia Study Group ALL studies (ALL941 [1994 to 2000], n=464; ALL2000 [2000 to 2004], n=305; and ALL2004 [2004 to 2010], n=326). ON was diagnosed in 16 patients, of whom 15 were symptomatic. The cumulative incidence of ON was 0.76% in ALL941, 0.35% in ALL2000, and 3.6% in ALL2004. The incidence of ON in ALL941/2000, in which only prednisolone was administered as a steroid, was significantly lower than that in ALL2004, in which dexamethasone was used as a partial substitute for prednisolone (P<0.01). In ALL2004, sex and age were significantly correlated with the incidence of ON (1.3% in boys vs. 6.7% in girls, P=0.0132; 0.42% for age <10 y vs. 15.6% for age ≥10 y, P<0.0001), suggesting that girls aged 10 years and above are at a greater risk of ON onset. These results indicate that the risk of ON should be considered when administering dexamethasone as part of ALL protocol treatment in girls aged 10 years and above.

  14. CD19/CD22 Chimeric Antigen Receptor T Cells and Chemotherapy in Treating Children or Young Adults With Recurrent or Refractory CD19 Positive B Acute Lymphoblastic Leukemia

    Science.gov (United States)

    2017-11-20

    B Acute Lymphoblastic Leukemia; CD19 Positive; Minimal Residual Disease; Philadelphia Chromosome Positive; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Refractory Acute Lymphoblastic Leukemia

  15. Combination Chemotherapy in Treating Young Patients With Newly Diagnosed High-Risk B Acute Lymphoblastic Leukemia and Ph-Like TKI Sensitive Mutations

    Science.gov (United States)

    2018-02-02

    B Acute Lymphoblastic Leukemia; Central Nervous System Leukemia; Ph-Like Acute Lymphoblastic Leukemia; Testicular Leukemia; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Childhood Acute Lymphoblastic Leukemia

  16. Shorter maintenance therapy in childhood Acute Lymphoblastic Leukemia. The experience of the prospective, randomized Brazilian GBTLI ALL-93 protocol.

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    Silvia Regina Brandalise

    2016-10-01

    Full Text Available Maintenance therapy is an important phase of the childhood ALL treatment, requiring 2-year long therapy adherence of the patients and families. Weekly methotrexate (MTX with daily 6-mercaptopurine (6MP constitutes the backbone of maintenance therapy. Reduction in the maintenance therapy could overweight problems related with poverty of children with ALL living in Limited-Income countries (LIC. Objective: To compare, prospectively, the EFS rates of children with ALL treated according to two maintenance regimens: 18 vs 24 months duration. Materials and Methods: From October 1993 to September 1999, 867 consecutive untreated ALL patients 10 years and high WBC at diagnosis. Overall death in remission rate was 6.85% (56 patients. Deaths during maintenance were 13 in group 1 and 12 in group 2, all due to infection. Over 15 years of follow-up, two patients both from Group 2 presented a second malignancy (Hodgkin’s disease and thyroid carcinoma after 8.3 and 11 years off therapy, respectively. Conclusion: Six-month reduction of maintenance therapy in ALL children treated according to the GBTLI ALL-93 protocol, provided the same overall outcome as 2-year duration regimen.

  17. [Necrotizing fasciitis, myositis, arthritis, and streptococcal toxic shock syndrome caused by group G Streptococcus. Report of one case].

    Science.gov (United States)

    Ayala-Gaytán, Juan Jacobo; Martínez-Vela, Ángel; Náñez-Terreros, Homero; Guajardo-Lara, Claudia Elena; Valdovinos-Chávez, Salvador Bruno

    2014-01-01

    Necrotizing fasciitis (NF), myositis, and streptococcal toxic shock syndrome (STSS) associated with group G ß-hemolytic streptococcus (GGS) occasionally coincide. We describe a case of GGS simultaneously occurring with NF, myositis, arthritis, and STSS in an 83-year-old woman with sequelae of cerebrovascular disease, hospitalized after two days of fever and with a painful swollen left foot. She was hypotensive, her foot had purplish discoloration, which showed blisters spreading to the lower third of the leg, and no crepitus was present. Fluid, vasopressive support, tigecyclin, and clindamycin were used. Debrided tissue and fluid aspirated from the knee joint revealed Gram-positive cocci. The patient developed renal and respiratory failure on the fifth day, requiring support. She underwent amputation above the knee of the left leg, after which her condition improved. She was discharged one month later. GGS can cause life-threatening infections such as NF, myositis, and/or STSS. GGS usually afflicts aging patients with comorbid states, and occasionally healthy subjects.

  18. Efficacy and Toxicity of Intrathecal Liposomal Cytarabine in First-line Therapy of Childhood Acute Lymphoblastic Leukemia

    DEFF Research Database (Denmark)

    Levinsen, Mette; Harila-Saari, Arja; Grell, Kathrine

    2016-01-01

    We investigated efficacy and toxicity of replacing conventional triple (cytarabine, methotrexate, and hydrocortisone) intrathecal therapy (TIT) with liposomal cytarabine during maintenance therapy among 40 acute lymphoblastic leukemia patients. Twenty-eight of 29 patients in the TIT arm received...... TIT and 9/11 in the liposomal cytarabine arm received liposomal cytarabine. Arachnoiditis occurred in all initial 5 patients given liposomal cytarabine and intrathecal prednisolone succinate. Subsequently liposomal cytarabine was given with systemic dexamethasone. Neurotoxicity occurred at 6....../27 liposomal cytarabine administrations with concomitant dexamethasone (22%). More liposomal cytarabine-treated patients experienced neurotoxicity in relation to intrathecal therapy during at least 1 cycle compared with TIT-treated patients (6/9 [67%] vs. 3/28 [11%], P=0.002). Apart from intermittent lower...

  19. BMS-214662 in Treating Patients With Acute Leukemia, Myelodysplastic Syndrome, or Chronic Myeloid Leukemia

    Science.gov (United States)

    2013-01-22

    Adult Acute Promyelocytic Leukemia (M3); Blastic Phase Chronic Myelogenous Leukemia; Childhood Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Relapsing Chronic Myelogenous Leukemia

  20. Childhood dermatomyositis recurring in adulthood half a century later.

    Science.gov (United States)

    Ismajli, M; Nikiphorou, E; Young, A

    2013-09-02

    A 62-year-old woman presented to the emergency department with malaise, lethargy and proximal muscle weakness. She had a similar presentation in childhood. A muscle biopsy was inconclusive, however, she was treated for a presumptive diagnosis of inflammatory myositis. In a second flare in childhood, she developed proximal muscle weakness and calcinosis cutis. A muscle biopsy was consistent with juvenile dermatomyositis. She was treated with corticosteroids, however, she relapsed again 1 year later, requiring a prolonged course of corticosteroids, which led to remission and treatment was subsequently stopped. She remained well for 30 years without any relapses, however, at the age of 40 she was diagnosed with malignant melanoma, treated with local excision and radiotherapy. She had a further period of 22 years in good health, until her current presentation, with a relapse of dermatomyositis, 52 years after the last flare. She is currently in remission following successful immunosuppressive therapy.

  1. An autoimmune myositis-overlap syndrome associated with autoantibodies to nuclear pore complexes: description and long-term follow-up of the anti-Nup syndrome.

    Science.gov (United States)

    Senécal, Jean-Luc; Isabelle, Catherine; Fritzler, Marvin J; Targoff, Ira N; Goldstein, Rose; Gagné, Michel; Raynauld, Jean-Pierre; Joyal, France; Troyanov, Yves; Dabauvalle, Marie-Christine

    2014-11-01

    Autoimmune myositis encompasses various myositis-overlap syndromes, each being identified by the presence of serum marker autoantibodies. We describe a novel myositis-overlap syndrome in 4 patients characterized by the presence of a unique immunologic marker, autoantibodies to nuclear pore complexes. The clinical phenotype was characterized by prominent myositis in association with erosive, anti-CCP, and rheumatoid factor-positive arthritis, trigeminal neuralgia, mild interstitial lung disease, Raynaud phenomenon, and weight loss. The myositis was typically chronic, relapsing, and refractory to corticosteroids alone, but remitted with the addition of a second immunomodulating drug. There was no clinical or laboratory evidence for liver disease. The prognosis was good with 100% long-term survival (mean follow-up 19.5 yr).By indirect immunofluorescence on HEp-2 cells, sera from all 4 patients displayed a high titer of antinuclear autoantibodies (ANA) with a distinct punctate peripheral (rim) fluorescent pattern of the nuclear envelope characteristic of nuclear pore complexes. Reactivity with nuclear pore complexes was confirmed by immunoelectron microscopy. In a cohort of 100 French Canadian patients with autoimmune myositis, the nuclear pore complex fluorescent ANA pattern was restricted to these 4 patients (4%). It was not observed in sera from 393 adult patients with systemic sclerosis (n = 112), mixed connective tissue disease (n = 35), systemic lupus (n = 94), rheumatoid arthritis (n = 45), or other rheumatic diseases (n = 107), nor was it observed in 62 normal adults.Autoantibodies to nuclear pore complexes were predominantly of IgG isotype. No other IgG autoantibody markers for defined connective tissue diseases or overlap syndromes were present, indicating a selective and highly focused immune response. In 3 patients, anti-nuclear pore complex autoantibody titers varied in parallel with myositis activity, suggesting a pathogenic link to

  2. Acute pediatric rhabdomyolysis.

    Science.gov (United States)

    Watemberg, N; Leshner, R L; Armstrong, B A; Lerman-Sagie, T

    2000-04-01

    Rhabdomyolysis is a relatively common condition that may occur intermittently in chronic and inflammatory myopathy, muscular dystrophy, and metabolic myopathy. Rhabdomyolysis can also present acutely in otherwise healthy individuals. The list of etiologies for acute muscle cell lysis is enormous, with new causes described yearly. Series on acute pediatric rhabdomyolysis have not yet been published. This article describes a retrospective review of children admitted to the authors' institution during an 8-year period in whom rhabdomyolysis was recognized as a complication during their hospital stay. Patients with intermittent or relapsing rhabdomyolysis were excluded. Nineteen children were identified. Trauma (five cases), nonketotic hyperosmolar coma (two cases), viral myositis (two cases), dystonia (two cases), and malignant hyperthermia-related conditions (two cases) were the most common causes of rhabdomyolysis. Acute renal failure was the most frequent complication, occurring in 42% of cases. The mean age of renal failure patients was 13.9 years, compared to 8 years for non-renal failure children. Careful assessment of the initial urinalysis would have suggested a diagnosis of rhabdomyolysis in 9 of 16 patients tested.

  3. Outcome of Childhood Acute Lymphoblastic Leukaemia after Induction Therapy --- Three-Year Experience in a Tertiary Care Hospital in Bangladesh

    Directory of Open Access Journals (Sweden)

    M Belayet Hossain

    2017-01-01

    Full Text Available Background: The incidence of different malignancies is increasing among the world populations. Acute lymphoblastic leukaemia (ALL is the most common of all the paediatric malignancies. Response to induction therapy is one of the most important predictors of long term outcome of ALL. Objective: To see the immediate outcome of paediatric ALL patients following induction therapy. Materials and Methods: This retrospective study was conducted from January 2013 to December 2015. Total 221 paediatric ALL patients were included in this study. Diagnosis was based on history, examination, blast cells count on peripheral blood film and bone marrow study, CSF study and immunophenotyping of peripheral blood/bone marrow aspirate in patients who were financially capable. Among them, parents of 40 (18% patients did not agree to start chemotherapy. According to Modified UK ALL 2003 protocol (Regimen A & B 181 patients were given induction therapy (vincristine, prednisolone, L-asparaginase, and daunomycin in high risk patients. Among them 14 patients discontinued, 10 patients died during chemotherapy and rest 157 patients completed induction phase. Bone marrow study was repeated after completion of induction therapy and remission pattern was seen. Results: Out of 157 chemotherapy completed patients, 137 (87% went into complete remission (25% blast cells in the bone marrow. Ten (5.5% patients died due to bleeding, febrile neutropenia and sepsis during the course of induction therapy. Conclusion: ALL in children is curable with effective chemotherapy. Poverty, ignorance and misconception regarding outcome are responsible for refusal and discontinuation of chemotherapy in third world countries like Bangladesh. Mortality and treatment cost can be reduced with the improvement of the facilities for isolation, barrier nursing and supportive treatment, and by creating awareness.

  4. CYP3A5 ∗ 3 genetic polymorphism is associated with childhood acute lymphoblastic leukemia risk: A meta-analysis.

    Science.gov (United States)

    Ma, Li-Min; Liu, Hong-Chao; Ruan, Lin-Hai; Feng, Yan-Ming

    2015-01-01

    Several studies have investigated the association between CYP3A5 FNx01 3 genetic polymorphism and acute lymphoblastic leukemia (ALL) risk in children, but have yielded controversial results. Therefore, we performed a meta-analysis to evaluate synthetically the effect of CYP3A5 FNx01 3 polymorphism on the risk of ALL in children. Case-control studies investigating the relationship between CYP3A5 FNx01 3 genetic polymorphism and ALL risk in children were included. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to assess the strength of association between CYP3A5 FNx01 3 polymorphism and ALL risk in children. Q-statistic test was used to evaluate the heterogeneity and publication bias was assessed through funnel plot. In total, five case-control studies with 1070 cases and 1125 controls were included in the meta-analysis. Based on the results of heterogeneity, fixed-effects or random-effects models were applied to estimate the pooled ORs. The pooled ORs (95% CIs) for CYP3A5 FNx01 3 heterozygous mutant, homozygous mutant, and (heterozygous + homozygous) mutant were 1.47 (0.97-2.21), 1.05 (0.62-1.79), and 1.67 (1.14-2.44) with P = 0.07, 0.86, and 0.009, respectively. In subgroup analysis, the Z values of CYP3A5 FNx01 3 (heterozygous + homozygous) mutant and children with ALL in Asian and Caucasian populations were 1.34 and 2.51 with P = 0.18 and 0.01, respectively. No significant publication bias was detected by funnel plot. The current meta-analysis showed that there was association between CYP3A5 FNx01 3 polymorphism and the altered risk of ALL in children, especially in Caucasian populations.

  5. Father's occupational exposure to carcinogenic agents and childhood acute leukemia: a new method to assess exposure (a case-control study)

    Science.gov (United States)

    Perez-Saldivar, Maria Luisa; Ortega-Alvarez, Manuel Carlos; Fajardo-Gutierrez, Arturo; Bernaldez-Rios, Roberto; del Campo-Martinez, Maria de los Angeles; Medina-Sanson, Aurora; Palomo-Colli, Miguel Angel; Paredes-Aguilera, Rogelio; Martínez-Avalos, Armando; Borja-Aburto, Victor Hugo; Rodriguez-Rivera, Maria de Jesus; Vargas-Garcia, Victor Manuel; Zarco-Contreras, Jesus; Flores-Lujano, Janet; Mejia-Arangure, Juan Manuel

    2008-01-01

    Background Medical research has not been able to establish whether a father's occupational exposures are associated with the development of acute leukemia (AL) in their offspring. The studies conducted have weaknesses that have generated a misclassification of such exposure. Occupations and exposures to substances associated with childhood cancer are not very frequently encountered in the general population; thus, the reported risks are both inconsistent and inaccurate. In this study, to assess exposure we used a new method, an exposure index, which took into consideration the industrial branch, specific position, use of protective equipment, substances at work, degree of contact with such substances, and time of exposure. This index allowed us to obtain a grade, which permitted the identification of individuals according to their level of exposure to known or potentially carcinogenic agents that are not necessarily specifically identified as risk factors for leukemia. The aim of this study was to determine the association between a father's occupational exposure to carcinogenic agents and the presence of AL in their offspring. Methods From 1999 to 2000, a case-control study was performed with 193 children who reside in Mexico City and had been diagnosed with AL. The initial sample-size calculation was 150 children per group, assessed with an expected odds ratio (OR) of three and a minimum exposure frequency of 15.8%. These children were matched by age, sex, and institution with 193 pediatric surgical patients at secondary-care hospitals. A questionnaire was used to determine each child's background and the characteristics of the father's occupation(s). In order to determine the level of exposure to carcinogenic agents, a previously validated exposure index (occupational exposure index, OEI) was used. The consistency and validity of the index were assessed by a questionnaire comparison, the sensory recognition of the work area, and an expert's opinion. Results The

  6. Father's occupational exposure to carcinogenic agents and childhood acute leukemia: a new method to assess exposure (a case-control study

    Directory of Open Access Journals (Sweden)

    Rodriguez-Rivera Maria

    2008-01-01

    Full Text Available Abstract Background Medical research has not been able to establish whether a father's occupational exposures are associated with the development of acute leukemia (AL in their offspring. The studies conducted have weaknesses that have generated a misclassification of such exposure. Occupations and exposures to substances associated with childhood cancer are not very frequently encountered in the general population; thus, the reported risks are both inconsistent and inaccurate. In this study, to assess exposure we used a new method, an exposure index, which took into consideration the industrial branch, specific position, use of protective equipment, substances at work, degree of contact with such substances, and time of exposure. This index allowed us to obtain a grade, which permitted the identification of individuals according to their level of exposure to known or potentially carcinogenic agents that are not necessarily specifically identified as risk factors for leukemia. The aim of this study was to determine the association between a father's occupational exposure to carcinogenic agents and the presence of AL in their offspring. Methods From 1999 to 2000, a case-control study was performed with 193 children who reside in Mexico City and had been diagnosed with AL. The initial sample-size calculation was 150 children per group, assessed with an expected odds ratio (OR of three and a minimum exposure frequency of 15.8%. These children were matched by age, sex, and institution with 193 pediatric surgical patients at secondary-care hospitals. A questionnaire was used to determine each child's background and the characteristics of the father's occupation(s. In order to determine the level of exposure to carcinogenic agents, a previously validated exposure index (occupational exposure index, OEI was used. The consistency and validity of the index were assessed by a questionnaire comparison, the sensory recognition of the work area, and an

  7. Calcium and cholecalciferol supplementation provides no added benefit to nutritional counseling to improve bone mineral density in survivors of childhood acute lymphoblastic leukemia (ALL).

    Science.gov (United States)

    Kaste, S C; Qi, A; Smith, K; Surprise, H; Lovorn, E; Boyett, J; Ferry, R J; Relling, M V; Shurtleff, S A; Pui, C H; Carbone, L; Hudson, M M; Ness, K K

    2014-05-01

    We sought to improve lumbar spine bone mineral density (LS-BMD) in long-term survivors of childhood acute lymphoblastic leukemia (ALL) using calcium and cholecalciferol supplementation. This double-blind, placebo-controlled trial randomized 275 participants (median age, 17 [9-36.1] years) with age- and gender-specific LS-BMD Z-scores <0 to receive nutritional counseling with supplementation of 1,000 mg/day calcium and 800 International Unit cholecalciferol or placebo for 2 years. The primary outcome was change in LS-BMD assessed by quantitative computerized tomography (QCT) at 24 months. Linear regression models were employed to identify the baseline risk factors for low LS-BMD and to compare LS-BMD outcomes. Pre-randomization LS-BMD below the mean was associated with male gender (P = 0.0024), White race (P = 0.0003), lower body mass index (P < 0.0001), and cumulative glucocorticoid doses of ≥ 5,000 mg (P = 0.0012). One hundred eighty-eight (68%) participants completed the study; 77% adhered to the intervention. Mean LS-BMD change did not differ between survivors randomized to supplements (0.33 ± 0.57) or placebo (0.28 ± 0.56). Participants aged 9-13 years and those 22-35 years had the greatest mean increases in LS-BMD (0.50 ± 0.66 and 0.37 ± 0.23, respectively). Vitamin D insufficiency (serum 25[OH]D <30 ng/ml) found in 296 (75%), was not associated with LS-BMD outcomes (P = 0.78). Cholecalciferol and calcium supplementation provides no added benefit to nutritional counseling for improving LS-BMD among adolescent and young adult survivors of ALL (93% of whom had LS-BMD Z-scores above the mean at study entry). © 2014 Wiley Periodicals, Inc.

  8. Inherent illnesses and attacks: an ethnographic study of interpretations of childhood Acute Respiratory Infections (ARIs) in Manhiça, southern Mozambique

    Science.gov (United States)

    2011-01-01

    Background Pneumonia is a leading cause of childhood hospitalisation and child mortality in Africa. This study explores local interpretations of Acute Respiratory Infections (ARIs), focusing on caretakers of children under five in the context of hospital care seeking. Methods The study took place in Manhiça, southern Mozambique and used Focused Ethnographic Study tools (FES) including field exercises and interviews. Results Understandings of terms used to describe ARIs differed between caretakers and hospital staff. Children's sicknesses that hospital staff diagnosed as ARIs were interpreted by caretakers as intermittent "attacks" of xifuva, a permanent, inherent and incurable chest illness. Caretakers thought that it was possible to manage and treat the attacks, which were caused by immediate natural factors such as food or the weather, but not the underlying illness, which was seen as having more indirect and social causes. Explanations of illness could not be neatly separated into pluralistic categories, but were characterised by syncretism, with "lay" and "biomedical" terms and concepts intermingling in practical care-seeking interactions between caretakers and health staff. Conclusions Health promotion should take into account the syncretism involved in explanations of ARIs in the context of practical care seeking for children. In doing so, it should draw upon lay interpretations and terminologies in order to stress the importance of seeking hospital care for all xifuva-type illnesses as well as seeking care for any subsequent attacks of an already diagnosed xifuva. However, this should be undertaken with awareness that the meanings of the terms used in practical care-seeking interactions may change over time. Health communication about ARIs should therefore be ongoing and evidence-based, even if ARIs appear to be well understood. PMID:21752260

  9. Inherent illnesses and attacks: an ethnographic study of interpretations of childhood Acute Respiratory Infections (ARIs in Manhiça, southern Mozambique

    Directory of Open Access Journals (Sweden)

    Pell Christopher

    2011-07-01

    Full Text Available Abstract Background Pneumonia is a leading cause of childhood hospitalisation and child mortality in Africa. This study explores local interpretations of Acute Respiratory Infections (ARIs, focusing on caretakers of children under five in the context of hospital care seeking. Methods The study took place in Manhiça, southern Mozambique and used Focused Ethnographic Study tools (FES including field exercises and interviews. Results Understandings of terms used to describe ARIs differed between caretakers and hospital staff. Children's sicknesses that hospital staff diagnosed as ARIs were interpreted by caretakers as intermittent "attacks" of xifuva, a permanent, inherent and incurable chest illness. Caretakers thought that it was possible to manage and treat the attacks, which were caused by immediate natural factors such as food or the weather, but not the underlying illness, which was seen as having more indirect and social causes. Explanations of illness could not be neatly separated into pluralistic categories, but were characterised by syncretism, with "lay" and "biomedical" terms and concepts intermingling in practical care-seeking interactions between caretakers and health staff. Conclusions Health promotion should take into account the syncretism involved in explanations of ARIs in the context of practical care seeking for children. In doing so, it should draw upon lay interpretations and terminologies in order to stress the importance of seeking hospital care for all xifuva-type illnesses as well as seeking care for any subsequent attacks of an already diagnosed xifuva. However, this should be undertaken with awareness that the meanings of the terms used in practical care-seeking interactions may change over time. Health communication about ARIs should therefore be ongoing and evidence-based, even if ARIs appear to be well understood.

  10. Body composition and bone health in long-term survivors of acute lymphoblastic leukaemia in childhood and adolescence: the protocol for a cross-sectional cohort study.

    Science.gov (United States)

    Barr, Ronald; Nayiager, Trishana; Gordon, Christopher; Marriott, Christopher; Athale, Uma

    2015-01-20

    Success in the treatment of young people with cancer, as measured conventionally by survival rates, is mitigated by late effects of therapy that impose a burden of morbidity and limit life expectancy. Among these adverse sequelae are altered body composition, especially obesity, and compromised bone health in the form of osteoporosis and increased fragility. These outcomes are potentially reversible and even preventable. This study will examine measures of body composition and bone health in long-term survivors of acute lymphoblastic leukaemia (ALL) in childhood and adolescence. These measures will be complemented by measures of physical activity and health-related quality of life (HRQL). Survivors of ALL who are at least 10 years from diagnosis, following treatment on uniform protocols, will undergo measurements of body mass index; triceps skin fold thickness and mid-upper arm circumference; fat mass, lean body mass, skeletal muscle mass and bone mineral density by dual energy X-ray absorptiometry; trabecular and cortical bone indices and muscle density by peripheral quantitative CT; physical activity by the Habitual Activity Estimation Scale; and HRQL by Health Utilities Index instruments. Descriptive measures will be used for continuous variables and number (percent) for categorical variables. Associations between variables will be assessed using Fisher's exact t test and the χ(2) test; correlations will be tested by the Pearson correlation coefficient. The study is approved by the institutional research ethics board and is supported by a competitive funding award. Dissemination of the results will occur by presentations to scientific meetings and publications in peer-reviewed journals, and by posting summaries of the results on websites accessed by adolescent and young adult survivors of cancer. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  11. Lower extremity peak force and gait kinematics in individuals with inclusion body myositis

    Science.gov (United States)

    Davenport, Todd E.; Benson, Kimberly; Baker, Stephanie; Gracey, Christopher; Rakocevic, Goran; McElroy, Beverly; Dalakas, Marinos; Shrader, Joseph A.; Harris-Love, Michael O.

    2015-01-01

    Objective To determine the relationship between peak isometric muscle force and temporal characteristics of gait in individuals with sporadic inclusion body myositis (s-IBM). Patients and Methods An observational study of 42 individuals with s-IBM (12 female; age: 61.6 ±7.3 years [mean ±standard deviation]; disease duration 8.9 ±4.3 years) was conducted at a Federal hospital. Peak isometric force measurements for lower extremity (LE) muscle groups were obtained using quantitative muscle testing. Temporal characteristics of gait during habitual and fast walking conditions were measured using a portable gait analysis system. Results All observed muscle force values were significantly lower than predicted values (p gait speed and cadence were gait cycle time was 133% of normal, while gait speed and cadence were 58% and 78%, respectively, of normative literature values. Scaled LE peak muscle forces showed significant moderate correlations with the temporal gait variables. Weaker subjects demonstrated greater limitations in gait speed and cadence compared to stronger subjects (p gait. Conclusions Muscle weakness associated with s-IBM disease activity may contribute to diminished gait kinematics. Temporal features of gait are not substantially influenced by knee extensor weakness alone, as the knee flexors and ankle plantar flexors play a compensatory role in maintaining the walking ability of individuals with s-IBM. PMID:25201017

  12. Anesthetic Considerations of Sporadic Inclusion Body Myositis in an Elderly Man With Orthopedic Trauma.

    Science.gov (United States)

    Steck, Dominik T; Choi, Christine; Gollapudy, Suneeta; Pagel, Paul S

    2016-04-01

    Sporadic inclusion body myositis (IBM) is an inflammatory myopathy characterized by progressive asymmetric extremity weakness, oropharyngeal dysphagia, and the potential for exaggerated sensitivity to neuromuscular blockers and respiratory compromise. The authors describe their management of a patient with IBM undergoing urgent orthopedic surgery. An 81-year-old man with IBM suffered a left intertrochanteric femoral fracture after falling down stairs. His IBM caused progressive left proximal lower extremity, bilateral distal upper extremity weakness (left > right), and oropharyngeal dysphagia (solid food, pills). He denied dyspnea, exercise intolerance, and a history of aspiration. Because respiratory insufficiency resulting from diaphragmatic dysfunction and prolonged duration of action of neuromuscular blockers may occur in IBM, the authors avoided using a neuromuscular blocker. After applying cricoid pressure, anesthesia was induced using intravenous lidocaine, propofol, remifentanil followed by manual ventilation with inhaled sevoflurane in oxygen. Endotracheal intubation was accomplished without difficulty; anesthesia was then maintained using remifentanil and sevoflurane. The fracture was repaired with a trochanteric femoral nail. The patient was extubated without difficulty and made an uneventful recovery. In summary, there is a lack of consensus about the use of neuromuscular blockers in patients with IBM. The authors avoided these drugs and were able to easily secure the patient's airway and maintain adequate muscle relaxation using a balanced sevoflurane-remifentanil anesthetic. Clinical trials are necessary to define the pharmacology of neuromuscular blockers in patients with IBM and determine whether use of these drugs contributes to postoperative respiratory insufficiency in these vulnerable patients.

  13. Intramuscular inoculation of cattle with Sarcocystis antigen results in focal eosinophilic myositis.

    Science.gov (United States)

    Vangeel, L; Houf, K; Geldhof, P; Nollet, H; Vercruysse, J; Ducatelle, R; Chiers, K

    2012-02-10

    Bovine eosinophilic myositis (BEM) is a subclinical myopathy characterized by multifocal white to grey-green discolorations in skeletal muscles, heart, tongue and oesophagus. These lesions are found at slaughter or during meat cutting and result in considerable economic losses. The etiology and pathogenesis are unclear, although it has been suggested, that Sarcocystis species are involved. To elucidate their role, two calves were repeatedly injected intramuscularly with adjuvanted Sarcocystis antigen. The morphological changes at the injection sites in these calves were histologically and immunohistochemically compared to spontaneous lesions from 44 BEM condemned carcasses sampled in slaughterhouses. Experimental intramuscular injection of Sarcocystis antigen resulted in lesions at the injection sites that were similar to the lesions of natural cases of BEM. They were characterized by massive infiltration of eosinophilic granulocytes, reactive macrophages (MAC387(+) cells), T-cells (CD3(+)) and B-cells (CD20(+)). Both in the experimental and in the natural cases, COX-2 expression was present in endothelial cells adjacent to lesional areas. MHC class II(+) staining was found amongst others in muscle cells surrounding the lesion. These results show that Sarcocystis antigens can induce an inflammatory response in bovine muscle having the characteristics of natural BEM. Copyright © 2011 Elsevier B.V. All rights reserved.

  14. Biological Therapy in Treating Patients With Advanced Myelodysplastic Syndrome, Acute or Chronic Myeloid Leukemia, or Acute Lymphoblastic Leukemia Who Are Undergoing Stem Cell Transplantation

    Science.gov (United States)

    2017-03-27

    Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); B-cell Adult Acute Lymphoblastic Leukemia; B-cell Childhood Acute Lymphoblastic Leukemia; Childhood Chronic Myelogenous Leukemia; Childhood Myelodysplastic Syndromes; Chronic Myelomonocytic Leukemia; Essential Thrombocythemia; Polycythemia Vera; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; T-cell Adult Acute Lymphoblastic Leukemia; T-cell Childhood Acute Lymphoblastic Leukemia

  15. Oral methotrexate/6-mercaptopurine may be superior to a multidrug LSA2L2 Maintenance therapy for higher risk childhood acute lymphoblastic leukemia: results from the NOPHO ALL-92 study

    DEFF Research Database (Denmark)

    Schmiegelow, Kjeld; Heyman, Mats; Kristinsson, Jon

    2009-01-01

    The importance of maintenance therapy for higher risk childhood acute lymphoblastic leukemia (ALL) is uncertain. Between 1992 and 2001 the Nordic Society for Pediatric Haematology/Oncology compared in a nonrandomized study conventional oral methotrexate (MTX)/6-mercaptopurine (6MP) maintenance...... therapy with a multidrug cyclic LSA2L2 regimen. 135 children with B-lineage ALL and a white blood count > or =50 x 10/L and 98 children with T-lineage ALL were included. Of the 234 patients, the 135 patients who received MTX/6MP maintenance therapy had a lower relapse risk than the 98 patients who...

  16. Gemtuzumab Ozogamicin in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia or Acute Promyelocytic Leukemia

    Science.gov (United States)

    2017-05-25

    Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Promyelocytic Leukemia (M3); Childhood Acute Promyelocytic Leukemia (M3); Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Myeloid Leukemia

  17. Automated diagnosis of myositis from muscle ultrasound: Exploring the use of machine learning and deep learning methods.

    Directory of Open Access Journals (Sweden)

    Philippe Burlina

    Full Text Available To evaluate the use of ultrasound coupled with machine learning (ML and deep learning (DL techniques for automated or semi-automated classification of myositis.Eighty subjects comprised of 19 with inclusion body myositis (IBM, 14 with polymyositis (PM, 14 with dermatomyositis (DM, and 33 normal (N subjects were included in this study, where 3214 muscle ultrasound images of 7 muscles (observed bilaterally were acquired. We considered three problems of classification including (A normal vs. affected (DM, PM, IBM; (B normal vs. IBM patients; and (C IBM vs. other types of myositis (DM or PM. We studied the use of an automated DL method using deep convolutional neural networks (DL-DCNNs for diagnostic classification and compared it with a semi-automated conventional ML method based on random forests (ML-RF and "engineered" features. We used the known clinical diagnosis as the gold standard for evaluating performance of muscle classification.The performance of the DL-DCNN method resulted in accuracies ± standard deviation of 76.2% ± 3.1% for problem (A, 86.6% ± 2.4% for (B and 74.8% ± 3.9% for (C, while the ML-RF method led to accuracies of 72.3% ± 3.3% for problem (A, 84.3% ± 2.3% for (B and 68.9% ± 2.5% for (C.This study demonstrates the application of machine learning methods for automatically or semi-automatically classifying inflammatory muscle disease using muscle ultrasound. Compared to the conventional random forest machine learning method used here, which has the drawback of requiring manual delineation of muscle/fat boundaries, DCNN-based classification by and large improved the accuracies in all classification problems while providing a fully automated approach to classification.

  18. Automated diagnosis of myositis from muscle ultrasound: Exploring the use of machine learning and deep learning methods

    Science.gov (United States)

    Burlina, Philippe; Billings, Seth; Joshi, Neil

    2017-01-01

    Objective To evaluate the use of ultrasound coupled with machine learning (ML) and deep learning (DL) techniques for automated or semi-automated classification of myositis. Methods Eighty subjects comprised of 19 with inclusion body myositis (IBM), 14 with polymyositis (PM), 14 with dermatomyositis (DM), and 33 normal (N) subjects were included in this study, where 3214 muscle ultrasound images of 7 muscles (observed bilaterally) were acquired. We considered three problems of classification including (A) normal vs. affected (DM, PM, IBM); (B) normal vs. IBM patients; and (C) IBM vs. other types of myositis (DM or PM). We studied the use of an automated DL method using deep convolutional neural networks (DL-DCNNs) for diagnostic classification and compared it with a semi-automated conventional ML method based on random forests (ML-RF) and “engineered” features. We used the known clinical diagnosis as the gold standard for evaluating performance of muscle classification. Results The performance of the DL-DCNN method resulted in accuracies ± standard deviation of 76.2% ± 3.1% for problem (A), 86.6% ± 2.4% for (B) and 74.8% ± 3.9% for (C), while the ML-RF method led to accuracies of 72.3% ± 3.3% for problem (A), 84.3% ± 2.3% for (B) and 68.9% ± 2.5% for (C). Conclusions This study demonstrates the application of machine learning methods for automatically or semi-automatically classifying inflammatory muscle disease using muscle ultrasound. Compared to the conventional random forest machine learning method used here, which has the drawback of requiring manual delineation of muscle/fat boundaries, DCNN-based classification by and large improved the accuracies in all classification problems while providing a fully automated approach to classification. PMID:28854220

  19. Injection of Botulinum Toxin a to Upper Esophageal Sphincter for Oropharyngeal Dysphagia in Two Patients with Inclusion Body Myositis

    Directory of Open Access Journals (Sweden)

    Louis WC Liu

    2004-01-01

    Full Text Available Inclusion body myositis (IBM is a progressive degenerative skeletal muscle disease leading to weakening and atrophy of both proximal and distal muscles. Dysphagia is reported in up to 86% of IBM patients. Surgical cricopharyngeal myotomy may be effective for cricopharyngeal dysphagia and there is one published report that botulinum toxin A, injected into the cricopharyngeus muscle using a hypopharyngoscope under general anesthesia, relieved IBM-associated dysphagia. This report presents the first documentation of botulinum toxin A injection into the upper esophageal sphincter using a flexible esophagogastroduodenoscope under conscious sedation, to reduce upper esophageal sphincter pressure and successfully alleviate oropharyngeal dysphagia in two IBM patients.

  20. Mechanical Ventilation Weaning in Inclusion Body Myositis: Feasibility of Isokinetic Inspiratory Muscle Training as an Adjunct Therapy

    Directory of Open Access Journals (Sweden)

    Leonardo Cordeiro de Souza

    2014-01-01

    Full Text Available Inclusion body myositis is a rare myopathy associated with a high rate of respiratory complications. This condition usually requires prolonged mechanical ventilation and prolonged intensive care stay. The unsuccessful weaning is mainly related to respiratory muscle weakness that does not promptly respond to immunosuppressive therapy. We are reporting a case of a patient in whom the use of an inspiratory muscle-training program which started after a two-week period of mechanical ventilation was associated with a successful weaning in one week and hospital discharge after 2 subsequent weeks.

  1. Hepatic sinusoidal obstruction syndrome during maintenance therapy of childhood acute lymphoblastic leukemia is associated with continuous asparaginase therapy and mercaptopurine metabolites.

    Science.gov (United States)

    Toksvang, Linea Natalie; De Pietri, Silvia; Nielsen, Stine N; Nersting, Jacob; Albertsen, Birgitte K; Wehner, Peder S; Rosthøj, Steen; Lähteenmäki, Päivi M; Nilsson, Daniel; Nystad, Tove A; Grell, Kathrine; Frandsen, Thomas L; Schmiegelow, Kjeld

    2017-09-01

    Hepatic sinusoidal obstruction syndrome (SOS) during treatment of childhood acute lymphoblastic leukemia (ALL) has mainly been associated with 6-thioguanine. The occurrence of several SOS cases after the introduction of extended pegylated asparaginase (PEG-asparaginase) therapy in the Nordic Society of Paediatric Haematology and Oncology (NOPHO) ALL2008 protocol led us to hypothesize that PEG-asparaginase, combined with other drugs, may trigger SOS during 6-thioguanine-free maintenance therapy. In children with ALL treated in Denmark according to the NOPHO ALL2008 protocol, we investigated the risk of SOS during methotrexate (MTX)/6-mercaptopurine (6MP) maintenance therapy that included PEG-asparaginase until week 33 (randomized to two- vs. six-week intervals), as well as alternating high-dose MTX or vincristine/dexamethasone pulses every four weeks. Among 130 children receiving PEG-asparaginase biweekly, 29 developed SOS (≥2 criteria: hyperbilirubinemia, hepatomegaly, ascites, weight gain ≥2.5%, unexplained thrombocytopenia <75 × 109 l-1 ) at a median of 30 days (interquartile range [IQR]: 17-66) into maintenance (cumulative incidence: 27%). SOS cases fulfilling one, two, or three Ponte di Legno criteria were classified as possible (n = 2), probable (n = 8), or verified (n = 19) SOS, respectively. Twenty-six cases (90%) occurred during PEG-asparaginase treatment, including 21 (81%) within 14 days from the last chemotherapy pulse compared with the subsequent 14 days (P = 0.0025). Cytotoxic 6MP metabolites were significantly higher on PEG-asparaginase compared to after its discontinuation. Time-dependent Cox regression analysis showed increased SOS hazard ratio (HR) for erythrocyte levels of methylated 6MP metabolites (HR: 1.09 per 1,000 nmol/mmol hemoglobin increase, 95% confidence interval: 1.05-1.14). Six-week PEG-asparaginase intervals significantly reduced SOS-specific hazards (P < 0.01). PEG-asparaginase increases cytotoxic 6MP metabolite levels and risk

  2. ARID5B, IKZF1 and non-genetic factors in the etiology of childhood acute lymphoblastic leukemia: the ESCALE study.

    Directory of Open Access Journals (Sweden)

    Jérémie Rudant

    Full Text Available Genome-wide association studies (GWAS have identified that frequent polymorphisms in ARID5B and IKZF1, two genes involved in lymphoid differentiation, increase the risk of childhood acute lymphoblastic leukemia (ALL. These findings markedly modified the current field of research on the etiology of ALL. In this new context, the present exploratory study investigated the possible interactions between these at-risk alleles and the non-genetic suspected ALL risk factors that were of sufficient prevalence in the French ESCALE study: maternal use of home insecticides during pregnancy, preconception paternal smoking, and some proxies for early immune modulation, i.e. breastfeeding, history of common infections before age one year, and birth order. The analyses were based on 434 ALL cases and 442 controls of European origin, drawn from the nationwide population-based case-control study ESCALE. Information on non-genetic factors was obtained by standardized telephone interview. Interactions between rs10740055 in ARID5B or rs4132601 in IKZF1 and each of the suspected non-genetic factors were tested, with the SNPs coded as counts of minor alleles (trend variable. Statistical interactions were observed between rs4132601 and maternal insecticide use (p = 0.012, breastfeeding p = 0.017 and repeated early common infections (p = 0.0070, with allelic odds ratios (OR which were only increased among the children not exposed to insecticides (OR = 1.8, 95%CI: 1.3, 2.4, those who had been breastfed (OR = 1.8, 95%CI: 1.3, 2.5 and those who had had repeated early common infections (OR = 2.4, 95%CI: 1.5, 3.8. The allelic ORs were close to one among children exposed to insecticides, who had not been breastfed and who had had no or few common infections. Repeated early common infections interacted with rs10740055 (p = 0.018 in the case-only design. Further studies are needed to evaluate whether these observations of a modification of the effect of the at-risk alleles by

  3. Evaluation of Endocrine Late Complications in Childhood Acute Lymphoblastic Leukemia Survivors: A Report of a Single-Center Experience and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Cengiz Bayram

    2017-03-01

    Full Text Available Objective: Improvement in long-term survival in patients with acute lymphoblastic leukemia (ALL in childhood has led to the need for monitorization of treatment-related morbidity and mortality. In the current study, we aimed to evaluate endocrine side effects of treatment in ALL survivors who were in remission for at least 2 years. Materials and Methods: Sixty patients diagnosed with ALL, who were in remission for at least 2 years, were cross-sectionally evaluated for long-term endocrine complications. Results: The median age of the patients at the time of diagnosis, at the time of chemotherapy completion, and at the time of the study was 5 years (minimum-maximum: 1.7-13, 8 years (minimummaximum: 4.25-16, and 11.7 years (minimum-maximum: 7-22, respectively, and median follow-up time was 4 years (minimummaximum: 2-10.1. At least one complication was observed in 81.6% of patients. Vitamin D insufficiency/deficiency (46.6%, overweight/ obesity (33.3%, and dyslipidemia (23.3% were the three most frequent endocrine complications. Other complications seen in our patients were hyperparathyroidism secondary to vitamin D deficiency (15%, insulin resistance (11.7%, hypertension (8.3%, short stature (6.7%, thyroid function abnormality (5%, precocious puberty (3.3%, and decreased bone mineral density (1.7%. There were no statistically significant correlations between endocrine complications and age, sex, and radiotherapy, except vitamin D insufficiency/deficiency, which was significantly more frequent in pubertal ALL survivors compared to prepubertal ALL survivors (57.5% and 25%, respectively, p=0.011. Conclusion: A high frequency of endocrine complications was observed in the current study. The high frequency of late effects necessitates long-term surveillance of this population to better understand the incidence of late-occurring events and the defining of high-risk features that can facilitate developing intervention strategies for early detection and

  4. Danish Childhood Cancer Registry

    DEFF Research Database (Denmark)

    Schrøder, Henrik; Rechnitzer, Catherine; Wehner, Peder Skov

    2016-01-01

    AIM OF DATABASE: The overall aim is to monitor the quality of childhood cancer care in Denmark; to register late effects of treatment; to analyze complications of permanent central venous catheters (CVCs); to study blood stream infections in children with cancer; and to study acute toxicity of high......, and outcome of antimicrobial chemotherapy. DESCRIPTIVE DATA: Since 1985, 4,944 children below 15 years of age have been registered in the database. There has been no significant change in the incidence of childhood cancer in Denmark since 1985. The 5-year survival has increased significantly since 1985...

  5. Acute and late side effects to salivary glands and oral mucosa after head and neck radiotherapy in children and adolescents. Results of the "Registry for the evaluation of side effects after radiotherapy in childhood and adolescence".

    Science.gov (United States)

    Bölling, Tobias; Weege, Julia; Eich, Hans Theodor; Timmermann, Beate; Meyer, Frank-Michal; Rübe, Christian; Kortmann, Rolf-Dieter; Fischedick, Karin; Rödel, Claus; Koch, Raphael; Willich, Normann

    2015-08-01

    The registry for the evaluation of side effects after radiotherapy in childhood and adolescence (RiSK) was established to prospectively characterize radiation-associated side effects. The purpose of this analysis was to characterize side effects after radiotherapy to the head and neck in children and adolescents. Radiation doses have been collected across Germany since 2001. Acute and late side effects were characterized. Until January 2010, 133 patients (median age, 12.7 years) were recruited who had received radiotherapy to the salivary glands. Toxicity evaluation was available for 114 patients (median follow-up, 2.9 years). Acute and late toxicity significantly depended on the maximum radiation dose to the salivary glands. An increase of the mean value of maximum dose of 1 Gray (Gy) to the submandibular glands resulted in an odds ratio of 1.04 (range, 1.00-1.08; p = .039) for acute toxicities of the salivary glands and 1.08 (range, 1.03-1.13; p = .001) for acute mucosal toxicities. These data can be used for an individual risk assessment in pediatric head and neck radiotherapy. © 2014 Wiley Periodicals, Inc.

  6. Methotrexate/6-mercaptopurine maintenance therapy influences the risk of a second malignant neoplasm after childhood acute lymphoblastic leukemia: results from the NOPHO ALL-92 study

    DEFF Research Database (Denmark)

    Schmiegelow, Kjeld; Al-Modhwahi, Ibrahim; Andersen, Mette Klarskov

    2009-01-01

    = .07) were related to increased risk of SMN. Thiopurine methyltransferase (TPMT) methylates 6MP and its metabolites, and thus reduces cellular levels of cytotoxic 6-thioguanine nucleotides. Of 524 patients who had erythrocyte TPMT activity measured, the median TPMT activity in 9 patients developing......). This study indicates that the duration and intensity of 6MP/MTX maintenance therapy of childhood ALL may influence the risk of SMNs in childhood ALL....

  7. Advancing the Development of Patient-reported Outcomes for Adult Myositis at OMERACT 2016: An International Delphi Study.

    Science.gov (United States)

    Park, Jin Kyun; Mecoli, Christopher A; Alexanderson, Helene; Regardt, Malin; Christopher-Stine, Lisa; Casal-Domínguez, María; de Groot, Ingrid; Sarver, Catherine; Lundberg, Ingrid E; Bingham, Clifton O; Song, Yeong Wook

    2017-08-01

    To define a set of core patient-reported domains and respective instruments for use in idiopathic inflammatory myopathies (IIM). Previously, we reported a systematic literature review on patient-reported outcomes (PRO) in IIM followed by conducting international focus groups to elicit patient perspectives of myositis symptoms and effects. Based on qualitative content analysis of focus groups, an initial list of 26 candidate domains was constructed. We subsequently conducted an international modified Delphi survey to identify the importance of each of the 26 domains. Participants were asked to rate each domain on a scale of 0-10 (0 = not important, 10 = very important). In this first round of the Delphi survey, 643 patients participated from the United States (n = 543), Sweden (n = 49), and South Korea (n = 51). Of the 26 domains, 19 (73%) were rated of high importance (≥ 7/10). The top 5 domains were muscle symptoms, fatigue, interactions with healthcare, medication side effects, and pain. During Outcome Measures in Rheumatology (OMERACT) 2016, we discussed the goal for ultimate reduction in the number of domains and the importance of considering representation of healthcare providers from other specialties, caregivers, representatives of pharmaceutical industries, and regulatory authorities in the next rounds of Delphi to represent broader perspectives on IIM. Further prioritization and a reduction in the number of domains will be needed for the next Delphi. At the next biennial OMERACT meeting, we aim to present and seek voting on a Myositis Preliminary PRO Core Set to enable ultimate measure selection and development.

  8. Acute pulmonary embolism in childhood

    NARCIS (Netherlands)

    van Ommen, C. Heleen; Peters, Marjolein

    2006-01-01

    Pulmonary embolism is an uncommon, but potentially fatal disease in children. Most children with pulmonary embolism have underlying clinical conditions, of which the presence of a central venous catheter is the most frequent. The clinical presentation is often subtle, or masked by the underlying

  9. Childhood Stress

    Science.gov (United States)

    ... Safe Videos for Educators Search English Español Childhood Stress KidsHealth / For Parents / Childhood Stress What's in this ... and feel stress to some degree. Sources of Stress Stress is a function of the demands placed ...

  10. Childhood Obesity

    OpenAIRE

    Ahmad, Qazi Iqbal; Ahmad, Charoo Bashir; Ahmad, Sheikh Mushtaq

    2010-01-01

    Childhood obesity has important consequences for health and wellbeing both during childhood and also in later adult life. The rising prevalence of childhood obesity poses a major public health challenge in both developed and developing countries by increasing the burden of chronic non-communicable diseases. Despite the urgent need for effective preventative strategies, there remains disagreement over its definition due to a lack of evidence on the optimal cut-offs linking childhood BMI to dis...

  11. Childhood Cancer

    Science.gov (United States)

    ... Late for the Flu Vaccine? Eating Disorders Arrhythmias Childhood Cancer KidsHealth > For Parents > Childhood Cancer Print A A A What's in this ... in children, but can happen. The most common childhood cancers are leukemia , lymphoma , and brain cancer . As ...

  12. Daily supplementation of D-ribose shows no therapeutic benefits in the MHC-I transgenic mouse model of inflammatory myositis.

    Directory of Open Access Journals (Sweden)

    William Coley

    Full Text Available BACKGROUND: Current treatments for idiopathic inflammatory myopathies (collectively called myositis focus on the suppression of an autoimmune inflammatory response within the skeletal muscle. However, it has been observed that there is a poor correlation between the successful suppression of muscle inflammation and an improvement in muscle function. Some evidence in the literature suggests that metabolic abnormalities in the skeletal muscle underlie the weakness that continues despite successful immunosuppression. We have previously shown that decreased expression of a purine nucleotide cycle enzyme, adenosine monophosphate deaminase (AMPD1, leads to muscle weakness in a mouse model of myositis and may provide a mechanistic basis for muscle weakness. One of the downstream metabolites of this pathway, D-ribose, has been reported to alleviate symptoms of myalgia in patients with a congenital loss of AMPD1. Therefore, we hypothesized that supplementing exogenous D-ribose would improve muscle function in the mouse model of myositis. We treated normal and myositis mice with daily doses of D-ribose (4 mg/kg over a 6-week time period and assessed its effects using a battery of behavioral, functional, histological and molecular measures. RESULTS: Treatment with D-ribose was found to have no statistically significant effects on body weight, grip strength, open field behavioral activity, maximal and specific forces of EDL, soleus muscles, or histological features. Histological and gene expression analysis indicated that muscle tissues remained inflamed despite treatment. Gene expression analysis also suggested that low levels of the ribokinase enzyme in the skeletal muscle might prevent skeletal muscle tissue from effectively utilizing D-ribose. CONCLUSIONS: Treatment with daily oral doses of D-ribose showed no significant effect on either disease progression or muscle function in the mouse model of myositis.

  13. Sleep disordered breathing in a cohort of patients with sporadic inclusion body myositis.

    Science.gov (United States)

    Della Marca, Giacomo; Sancricca, Cristina; Losurdo, Anna; Di Blasi, Chiara; De Fino, Chiara; Morosetti, Roberta; Broccolini, Aldobrando; Testani, Elisa; Scarano, Emanuele; Servidei, Serenella; Mirabella, Massimiliano

    2013-08-01

    The aims of the study were: (1) to evaluate subjective sleep quality and daytime sleepiness in patients affected by sporadic inclusion-body myositis (IBM); (2) to define the sleep and sleep-related respiratory pattern in IBM patients. Thirteen consecutive adult patients affected by definite IBM were enrolled, six women and seven men, mean age 66.2 ± 11.1 years (range: 50-80). Diagnosis was based on clinical and muscle biopsy studies. All patients underwent subjective sleep evaluation (Pittsburgh Sleep Quality Index, PSQI and Epworth Sleepiness Scale, ESS), oro-pharingo-esophageal scintigraphy, pulmonary function tests, psychometric measures, anatomic evaluation of upper airways, and laboratory-based polysomnography. Findings in IBM patients were compared to those obtained from a control group of 25 healthy subjects (13 men and 12 women, mean age 61.9 ± 8.6 years). Disease duration was >10 years in all. Mean IBM severity score was 28.8 ± 5.4 (range 18-36). Dysphagia was present in 10 patients. Nine patients had PSQI scores ≥ 5; patients had higher mean PSQI score (IBM: 7.2 ± 4.7, CONTROLS: 2.76 ± 1.45, p=0.005); one patient (and no controls) had EES>9. Polysomnography showed that IBM patients, compared to controls, had lower sleep efficiency (IBM: 78.8 ± 12.0%, 94.0 ± 4.5%, p<0.001), more awakenings (IBM: 11.9 ± 11.0, CONTROLS: 5.2 ± 7.5, p=0.009) and increased nocturnal time awake (IBM: 121.2 ± 82.0 min., 46.12 ± 28.8 min., p=0.001). Seven Patients (and no controls) had polysomnographic findings consistent with sleep disordered breathing (SDB). Data suggest that sleep disruption, and in particular SDB, might be highly prevalent in IBM. Data indicate that IBM patients have poor sleep and high prevalence of SDB. Copyright © 2013 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  14. The long-term results of childhood acute lymphoblastic leukemia at two centers from Turkey: 15 years of experience with the ALL-BFM 95 protocol.

    Science.gov (United States)

    Güneş, Adalet Meral; Oren, Hale; Baytan, Birol; Bengoa, Sebnem Yılmaz; Evim, Melike Sezgin; Gözmen, Salih; Tüfekçi, Ozlem; Karapınar, Tuba Hilkay; Irken, Gülersu

    2014-10-01

    Dramatic progress in the treatment of childhood acute lymphoblastic leukemia (ALL) has been achieved during the last two decades in Western countries, where the 5-year event-free survival (EFS) rate has risen from 30 to 85 %. However, similarly high cure rates have not always been achieved in all centers in developing countries due to limited sources. We evaluated the treatment results of the ALL-Berlin-Frankfurt-Münster (BFM) 95 protocol as used between 1995 and 2009 in the pediatric hematology departments of two university hospitals. A retrospective analysis of 343 children newly diagnosed with ALL (M/F 200/143, median age 6.8 years) was performed. The overall survival (OS) and EFS according to age, initial leukocyte count, immunophenotype, chemotherapy responses (on days 8, 15, and 33), and risk groups were analyzed by Kaplan-Meier survival analysis. Median follow-up time was 6.4 years. Complete remission was achieved in 97 % of children. Five-year EFS and OS were found to be 78.4 and 79.9 %, respectively. Children younger than 6 years old had significantly better EFS and OS (83.7 and 85.2 %) than children aged ≥6 years (71.4 and 72.8 %). Adolescents achieved 63 % EFS and 65 % OS. Patients who had initial leukocyte counts of <20 × 10(9)/L had better EFS and OS (82.2 and 84.6 %) than children with higher initial leukocyte counts (72.6 and 72.6 %). EFS for B-cell precursor and T-cell ALL was 81.5 and 66.7 %, respectively. Children with a good response to prednisolone on day 8 (87 %) achieved significantly better EFS and OS (81.2 and 81.9 % vs. 55.3 and 60.5 %). Children whose bone marrow on day 15 was in complete remission had higher EFS and OS (83.7 and 86.6.1 % vs. 56.4 and 61.5 %). Children in the standard-risk and medium-risk groups obtained statistically significantly higher EFS (95.5 and 82.7 %) and OS (97.7 and 82.3 %) compared to the high-risk group (EFS 56.3 %, OS 63.4 %). The relapse rate was 14.8 %. The median relapse time from diagnosis was 23

  15. Treatment Option Overview (Adult Acute Lymphoblastic Leukemia)

    Science.gov (United States)

    ... Treatment Childhood AML Treatment Research Adult Acute Lymphoblastic Leukemia Treatment (PDQ®)–Patient Version General Information About Adult Acute Lymphoblastic Leukemia Go to Health Professional Version Key Points Adult ...

  16. Stages of Adult Acute Lymphoblastic Leukemia

    Science.gov (United States)

    ... Treatment Childhood AML Treatment Research Adult Acute Lymphoblastic Leukemia Treatment (PDQ®)–Patient Version General Information About Adult Acute Lymphoblastic Leukemia Go to Health Professional Version Key Points Adult ...

  17. Treatment Options for Adult Acute Myeloid Leukemia

    Science.gov (United States)

    ... Treatment Childhood AML Treatment Research Adult Acute Myeloid Leukemia Treatment (PDQ®)–Patient Version General Information About Adult Acute Myeloid Leukemia Go to Health Professional Version Key Points Adult ...

  18. Treatment Options for Adult Acute Lymphoblastic Leukemia

    Science.gov (United States)

    ... Treatment Childhood AML Treatment Research Adult Acute Lymphoblastic Leukemia Treatment (PDQ®)–Patient Version General Information About Adult Acute Lymphoblastic Leukemia Go to Health Professional Version Key Points Adult ...

  19. General Information about Adult Acute Lymphoblastic Leukemia

    Science.gov (United States)

    ... Treatment Childhood AML Treatment Research Adult Acute Lymphoblastic Leukemia Treatment (PDQ®)–Patient Version General Information About Adult Acute Lymphoblastic Leukemia Go to Health Professional Version Key Points Adult ...

  20. Stages of Adult Acute Myeloid Leukemia

    Science.gov (United States)

    ... Treatment Childhood AML Treatment Research Adult Acute Myeloid Leukemia Treatment (PDQ®)–Patient Version General Information About Adult Acute Myeloid Leukemia Go to Health Professional Version Key Points Adult ...

  1. Treatment Option Overview (Adult Acute Myeloid Leukemia)

    Science.gov (United States)

    ... Treatment Childhood AML Treatment Research Adult Acute Myeloid Leukemia Treatment (PDQ®)–Patient Version General Information About Adult Acute Myeloid Leukemia Go to Health Professional Version Key Points Adult ...

  2. General Information about Adult Acute Myeloid Leukemia

    Science.gov (United States)

    ... Treatment Childhood AML Treatment Research Adult Acute Myeloid Leukemia Treatment (PDQ®)–Patient Version General Information About Adult Acute Myeloid Leukemia Go to Health Professional Version Key Points Adult ...

  3. Childhood intestinal obstruction in Northwestern Nigeria

    African Journals Online (AJOL)

    of childhood intestinal obstruction in this study agrees with those reportedis'gi m3 from other parts of the coun- try. Mortality from childhood intestinal obstruction is still high in our environment. References. 1. Otu AA. Tropical surgical abdominal emergencies: acute intestinal obstruction. Postgrad. Doctor (Afr) 1992; 14: 51. 2.

  4. Acute muscular weakness in children

    Directory of Open Access Journals (Sweden)

    Ricardo Pablo Javier Erazo Torricelli

    Full Text Available ABSTRACT Acute muscle weakness in children is a pediatric emergency. During the diagnostic approach, it is crucial to obtain a detailed case history, including: onset of weakness, history of associated febrile states, ingestion of toxic substances/toxins, immunizations, and family history. Neurological examination must be meticulous as well. In this review, we describe the most common diseases related to acute muscle weakness, grouped into the site of origin (from the upper motor neuron to the motor unit. Early detection of hyperCKemia may lead to a myositis diagnosis, and hypokalemia points to the diagnosis of periodic paralysis. Ophthalmoparesis, ptosis and bulbar signs are suggestive of myasthenia gravis or botulism. Distal weakness and hyporeflexia are clinical features of Guillain-Barré syndrome, the most frequent cause of acute muscle weakness. If all studies are normal, a psychogenic cause should be considered. Finding the etiology of acute muscle weakness is essential to execute treatment in a timely manner, improving the prognosis of affected children.

  5. Supportive care for children with acute leukemia - Report of a survey on supportive care by the Dutch Childhood Leukemia Study Group. Part I

    NARCIS (Netherlands)

    Postma, A; Van Leeuwen, EF; Gerritsen, EJA; Roord, JJ; De vries-Hospers, HG

    1998-01-01

    The Dutch Childhood Leukemia Study Group celebrated its 20th anniversary by conducting a nationwide survey on supportive care for children with leukemia. Pediatricians were asked about daily practice and current perceptions with regard to supportive care. The results are discussed and compared to

  6. Characterization of DLK1+ cells emerging during skeletal muscle remodeling in response to myositis, myopathies, and acute injury

    DEFF Research Database (Denmark)

    Andersen, Ditte C; Petersson, Stine J; Jørgensen, Louise H

    2009-01-01

    , DLK1 was upregulated in all human myopathies analyzed, including Duchenne- and Becker muscular dystrophies. Substantial numbers of DLK1(+) satellite cells were observed in normal neonatal and Duchenne muscle, and furthermore, myogenic DLK1(+) cells were identified during muscle regeneration in animal...

  7. Orbital myositis and rheumatoid arthritis: case report Miosite orbitária e artrite reumatóide: relato de caso

    Directory of Open Access Journals (Sweden)

    CLÁUDIA B. PANFILIO

    2000-03-01

    Full Text Available Orbital myositis implies orbital inflammation confined to one or more of the extraocular muscles. The acute form responds well to high doses of oral corticosteroids tapered gradually, but it may recur or become chronic. We describe a 38 years old female who has been suffering from rheumatoid arthritis for six years. She developed diplopia as a result of a paralysis of the right and left rectus medialis muscle. MRI showed inflammatory process and thickness of the referred muscles. The patient had a total recovery with oral use of 80 mg methylpredinisolone daily. Two months after the first episode she developed a bilateral ophthalmoplegy. The patient improved with oral use of steroids the second time, but a paresis of the left rectus lateralis muscle remained. From the 156 cases we reviewed only three have been related to rheumatic diseases and none has been previously related to rheumatoid arthritis.Miosite orbitaria é a inflamação de um ou mais músculos extraoculares. A forma aguda responde ao tratamento com doses altas de esteróides, porém pode-se tornar recorrente ou crônica. Relatamos uma paciente de 38 anos de idade, portadora de artrite reumatoide há 6 anos, que apresentou diplopia e cefaléia de um mês de evolução. A ressonância magnética (RM de órbitas mostrou processo inflamatório e espessamento dos músculos reto mediais. A paciente apresentou recuperação completa após o uso de 80 mg/dia de metilprednisolona. Dois meses depois, ela apresentou oftalmoplegia bilateral que acometia toda a musculatura ocular extrínseca. Desta vez, a RM foi normal. A paciente melhorou com nova série do esteroide, porém permaneceu com paresia do músculo reto lateral esquerdo como sequela. Revisamos 153 casos de miosite orbitaria publicados; apenas três estavam relacionados com doenças reumatológicas e nenhum deles com artrite reumatóide.

  8. Radiation recall dermatitis, panniculitis, and myositis following cyclophosphamide therapy: histopathologic findings of a patient affected by multiple myeloma.

    Science.gov (United States)

    Borroni, Giovanni; Vassallo, Camilla; Brazzelli, Valeria; Martinoli, Sara; Ardigò, Marco; Alessandrino, Paolo Emilio; Borroni, Riccardo Giovanni; Franchini, Pietro

    2004-06-01

    Radiation recall dermatitis is one of the skin sequelae that may affect oncology patients. It occurs in a previously irradiated field, when subsequent chemotherapy is given. The eruption may be elicited by chemotherapy, even several months after radiotherapy. Its mechanism is poorly understood, and the histopathologic findings have received, to date, only sketchy descriptions. A 55-year-old male affected by multiple myeloma received radiation therapy both on his left coxofemoral area, and lumbar region (D11-L1). After cyclophosphamide administration, he developed 2 well defined square-shaped, infiltrated erythematoviolaceous plaques in the prior irradiated fields. Histopathologic findings revealed a diffusely fibrosclerosing process, involving deep dermis, hypodermis, as well as the underlying muscle, while sparing the epidermis and superficial-mid dermis. Histopathology was indistinguishable from deep radio-dermatitis, panniculitis, and myositis. This is the first case providing clear evidence of the causative role of cyclophosphamide in inducing a cutaneous and subcutaneous radiation recall reaction.

  9. Disease specificity of autoantibodies to cytosolic 5'-nucleotidase 1A in sporadic inclusion body myositis versus known autoimmune diseases.

    Science.gov (United States)

    Herbert, Megan K; Stammen-Vogelzangs, Judith; Verbeek, Marcel M; Rietveld, Anke; Lundberg, Ingrid E; Chinoy, Hector; Lamb, Janine A; Cooper, Robert G; Roberts, Mark; Badrising, Umesh A; De Bleecker, Jan L; Machado, Pedro M; Hanna, Michael G; Plestilova, Lenka; Vencovsky, Jiri; van Engelen, Baziel G; Pruijn, Ger J M

    2016-04-01

    The diagnosis of inclusion body myositis (IBM) can be challenging as it can be difficult to clinically distinguish from other forms of myositis, particularly polymyositis (PM). Recent studies have shown frequent presence of autoantibodies directed against cytosolic 5'-nucleotidase 1A (cN-1A) in patients with IBM. We therefore, examined the autoantigenicity and disease specificity of major epitopes of cN-1A in patients with sporadic IBM compared with healthy and disease controls. Serum samples obtained from patients with IBM (n=238), PM and dermatomyositis (DM) (n=185), other autoimmune diseases (n=246), other neuromuscular diseases (n=93) and healthy controls (n=35) were analysed for the presence of autoantibodies using immunodominant cN-1A peptide ELISAs. Autoantibodies directed against major epitopes of cN-1A were frequent in patients with IBM (37%) but not in PM, DM or non-autoimmune neuromuscular diseases (autoimmune diseases, particularly Sjögren's syndrome (SjS; 36%) and systemic lupus erythematosus (SLE; 20%). In summary, we found frequent anti-cN-1A autoantibodies in sera from patients with IBM. Heterogeneity in reactivity with the three immunodominant epitopes indicates that serological assays should not be limited to a distinct epitope region. The similar reactivities observed for SjS and SLE demonstrate the need to further investigate whether distinct IBM-specific epitopes exist. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  10. Prevalence of Gene Rearrangements in Mexican Children with Acute Lymphoblastic Leukemia: A Population Study—Report from the Mexican Interinstitutional Group for the Identification of the Causes of Childhood Leukemia

    Directory of Open Access Journals (Sweden)

    Vilma Carolina Bekker-Méndez

    2014-01-01

    Full Text Available Mexico has one of the highest incidences of childhood leukemia worldwide and significantly higher mortality rates for this disease compared with other countries. One possible cause is the high prevalence of gene rearrangements associated with the etiology or with a poor prognosis of childhood acute lymphoblastic leukemia (ALL. The aims of this multicenter study were to determine the prevalence of the four most common gene rearrangements [ETV6-RUNX1, TCF3-PBX1, BCR-ABL1, and MLL rearrangements] and to explore their relationship with mortality rates during the first year of treatment in ALL children from Mexico City. Patients were recruited from eight public hospitals during 2010–2012. A total of 282 bone marrow samples were obtained at each child’s diagnosis for screening by conventional and multiplex reverse transcription polymerase chain reaction to determine the gene rearrangements. Gene rearrangements were detected in 50 (17.7% patients. ETV6-RUNX1 was detected in 21 (7.4% patients, TCF3-PBX1 in 20 (7.1% patients, BCR-ABL1 in 5 (1.8% patients, and MLL rearrangements in 4 (1.4% patients. The earliest deaths occurred at months 1, 2, and 3 after diagnosis in patients with MLL, ETV6-RUNX1, and BCR-ABL1 gene rearrangements, respectively. Gene rearrangements could be related to the aggressiveness of leukemia observed in Mexican children.

  11. Prevalence of Gene Rearrangements in Mexican Children with Acute Lymphoblastic Leukemia: A Population Study—Report from the Mexican Interinstitutional Group for the Identification of the Causes of Childhood Leukemia

    Science.gov (United States)

    Bekker-Méndez, Vilma Carolina; Miranda-Peralta, Enrique; Núñez-Enríquez, Juan Carlos; Olarte-Carrillo, Irma; Guerra-Castillo, Francisco Xavier; Pompa-Mera, Ericka Nelly; Ocaña-Mondragón, Alicia; Bernáldez-Ríos, Roberto; Medina-Sanson, Aurora; Jiménez-Hernández, Elva; Amador-Sánchez, Raquel; Peñaloza-González, José Gabriel; de Diego Flores-Chapa, José; Fajardo-Gutiérrez, Arturo; Flores-Lujano, Janet; Rodríguez-Zepeda, María del Carmen; Dorantes-Acosta, Elisa María; Bolea-Murga, Victoria; Núñez-Villegas, Nancy; Velázquez-Aviña, Martha Margarita; Torres-Nava, José Refugio; Reyes-Zepeda, Nancy Carolina; González-Bonilla, Cesar; Mejía-Aranguré, Juan Manuel

    2014-01-01

    Mexico has one of the highest incidences of childhood leukemia worldwide and significantly higher mortality rates for this disease compared with other countries. One possible cause is the high prevalence of gene rearrangements associated with the etiology or with a poor prognosis of childhood acute lymphoblastic leukemia (ALL). The aims of this multicenter study were to determine the prevalence of the four most common gene rearrangements [ETV6-RUNX1, TCF3-PBX1, BCR-ABL1, and MLL rearrangements] and to explore their relationship with mortality rates during the first year of treatment in ALL children from Mexico City. Patients were recruited from eight public hospitals during 2010–2012. A total of 282 bone marrow samples were obtained at each child's diagnosis for screening by conventional and multiplex reverse transcription polymerase chain reaction to determine the gene rearrangements. Gene rearrangements were detected in 50 (17.7%) patients. ETV6-RUNX1 was detected in 21 (7.4%) patients, TCF3-PBX1 in 20 (7.1%) patients, BCR-ABL1 in 5 (1.8%) patients, and MLL rearrangements in 4 (1.4%) patients. The earliest deaths occurred at months 1, 2, and 3 after diagnosis in patients with MLL, ETV6-RUNX1, and BCR-ABL1 gene rearrangements, respectively. Gene rearrangements could be related to the aggressiveness of leukemia observed in Mexican children. PMID:25692130

  12. Individualized toxicity-titrated 6-mercaptopurine increments during high-dose methotrexate consolidation treatment of lower risk childhood acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Frandsen, Thomas Leth; Abrahamsson, Jonas; Lausen, Birgitte Frederiksen

    2011-01-01

    This study explored the feasibility and toxicity of individualized toxicity-titrated 6-mercaptopurine (6MP) dose increments during post-remission treatment with High-dose methotrexate (HDM) (5000 mg/m2, ×3) in 38 patients with Childhood (ALL). Patients were increased in steps of 25 mg 6MP/m2 per...... the remaining patients (P = 0·03). This study shows individualized toxicity-titrated 6MP dosing during consolidation is feasible without increased risk of toxicity....

  13. Childhood pre-B cell acute lymphoblastic leukemia with translocation t(1;19)(q21.1;p13.3) and two additional chromosomal aberrations involving chromosomes 1, 6, and 13: a case report.

    Science.gov (United States)

    Wafa, Abdulsamad; As'sad, Manar; Liehr, Thomas; Aljapawe, Abdulmunim; Al Achkar, Walid

    2017-04-07

    The translocation t(1;19)(q23;p13), which results in the TCF3-PBX1 chimeric gene, is one of the most frequent rearrangements observed in B cell acute lymphoblastic leukemia. It appears in both adult and pediatric patients with B cell acute lymphoblastic leukemia at an overall frequency of 3 to 5%. Most cases of pre-B cell acute lymphoblastic leukemia carrying the translocation t(1;19) have a typical immunophenotype with homogeneous expression of CD19, CD10, CD9, complete absence of CD34, and at least diminished CD20. Moreover, the translocation t(1;19) correlates with known clinical high risk factors, such as elevated white blood cell count, high serum lactate dehydrogenase levels, and central nervous system involvement; early reports indicated that patients with translocation t(1;19) had a poor outcome under standard treatment. We report the case of a 15-year-old Syrian boy with pre-B cell acute lymphoblastic leukemia with abnormal karyotype with a der(19)t(1;19)(q21.1;p13.3) and two yet unreported chromosomal aberrations: an interstitial deletion 6q12 to 6q26 and a der(13)t(1;13)(q21.1;p13). According to the literature, cases who are translocation t(1;19)-positive have a significantly higher incidence of central nervous system relapse than patients with acute lymphoblastic leukemia without the translocation. Of interest, central nervous system involvement was also seen in our patient. To the best of our knowledge, this is the first case of childhood pre-B cell acute lymphoblastic leukemia with an unbalanced translocation t(1;19) with two additional chromosomal aberrations, del(6)(q12q26) and t(1;13)(q21.3;p13), which seem to be recurrent and could influence clinical outcome. Also the present case confirms the impact of the translocation t(1;19) on central nervous system relapse, which should be studied for underlying mechanisms in future.

  14. Twins discordant for myositis and systemic lupus erythematosus show markedly enriched autoantibodies in the affected twin supporting environmental influences in pathogenesis

    OpenAIRE

    Gan, Lu; O’Hanlon, Terrance P.; Gordon, Aaron S; Rider, Lisa G.; Frederick W Miller; Burbelo, Peter D.

    2014-01-01

    Background Studies of twin pairs discordant for autoimmune conditions provide a unique opportunity to explore contributing factors triggered by complex gene-environment interactions. Methods In this cross-sectional study, thirty-one monozygotic or dizygotic twin pairs discordant for myositis or systemic lupus erythematosus (SLE), along with matched healthy controls were evaluated for antibodies against a panel of 21 autoantigens. Results Autoantibody profiling revealed that 42% of the affecte...

  15. Evaluation of Internal Echogenic Pattern of Masseter in Subjects with Myofascial Pain/ Myositis, Oral Submucous Fibrosis, Chewers, Bruxers and Healthy Individuals- A Preliminary Ultrasonographic Study.

    Science.gov (United States)

    Raghunandan Iyengar, Asha; Patil, Seema; Guddannanavar Karibasappa, Ganga; Beloor Vasudev, Subash; Kumar Joshi, Revan

    2016-12-01

    The masseter is generally involved in myofascial pain, myositis, oral submucous fibrosis (OSMF), bruxism, and in subjects with habitual tobacco/arecanut chewing. In all the above conditions, changes in the internal echogenic pattern on ultrasonography of the muscle may be observed. The present study aimed at evaluating the internal echogenic pattern of masseter by ultrasonography in subjects with various conditions affecting masster muscle. The study subjects were categorized into 5 groups consisting of 20 subjects each with the following conditions; Group 1: myofascial pain or myositis, Group 2: oral submucous fibrosis (OSMF), Group 3: habitual chewing of tobacco/arecanut without OSMF, Group 4: bruxism. Group 5 consisted of 20 healthy subjects. An ultrasonographic examination of masseter was performed in all subjects and the echogenic pattern was classified into Types I, II and III. The images were examined by two observers and inter-observer variability was assessed. Differences in internal echogenic pattern between study groups and control group was evaluated using Chi- square test. A good inter observer agreement was noted (k value= 0.8). An equal distribution of Types II and III echogenic pattern was noted in myofascial pain/myositis group. Type II was predominant in subjects with OSMF, habitual tobacco/arecanut chewing and bruxism. Type I was predominant in controls. The echogenic pattern differed significantly from controls in subjects with myofascial pain/myositis and OSMF (p=0.00001*, 0.0237* respectively), whereas in subjects with habitual tobacco/ arecanut chewing and bruxism, it did not differ significantly from controls (p=0.2482, 0.1223 respectively). Ultrasonographic examination of the echogenic pattern may help in understanding the nature of the disease process affecting the masseter muscle in various conditions.

  16. Frequency of autoantibodies and correlation with HLA-DRB1 genotype in sporadic inclusion body myositis (s-IBM): a population control study.

    Science.gov (United States)

    Rojana-Udomsart, Arada; Bundell, Christine; James, Ian; Castley, Alison; Martinez, Patricia; Christiansen, Frank; Hollingsworth, Peter; Mastaglia, Frank

    2012-08-15

    The frequency of myositis-associated and myositis-specific autoantibodies (AAb) was compared in 51 s-IBM patients and a population control group. Non-organ specific AAb (ANA, anti-Ro52, anti-Ro60, anti-La, anti-RNP) but not anti-thyroid peroxidase, anti-tissue transglutaminase or myositis-specific antibodies, were more frequent in s-IBM patients, and 14/51 (27%) had another autoimmune disease (Sjögren's syndrome, thyroiditis, psoriasis, vitiligo). The presence of AAb did not correlate with carriage of HLA-DRB1*0301, but there was a negative correlation between ANA/anti-Ro52 and carriage of HLA-DRB1*1301. The findings in this cohort confirm that patients with sIBM do not show evidence of a muscle-specific humoral immune process but have an increased frequency of non-organ specific AAb and other autoimmune disorders. Copyright © 2012 Elsevier B.V. All rights reserved.

  17. Flow Cytometric DNA index, G-band Karyotyping, and Comparative Genomic Hybridization in Detection of High Hyperdiploidy in Childhood Acute Lymphoblastic Leukemia

    DEFF Research Database (Denmark)

    Nygaard, Ulrikka; Larsen, Jacob; Kristensen, Tim D

    2006-01-01

    High hyperdiploid acute lymphoblastic leukemia in children is related to a good outcome. Because these patients may be stratified to a low-intensity treatment, we have investigated the sensitivity of flow cytometry (FCM), G-band karyotyping (GBK), and high-resolution comparative genomic hybridiza......High hyperdiploid acute lymphoblastic leukemia in children is related to a good outcome. Because these patients may be stratified to a low-intensity treatment, we have investigated the sensitivity of flow cytometry (FCM), G-band karyotyping (GBK), and high-resolution comparative genomic...

  18. Danish Childhood Cancer Registry

    DEFF Research Database (Denmark)

    Schrøder, Henrik; Rechnitzer, Catherine; Wehner, Peder Skov

    2016-01-01

    AIM OF DATABASE: The overall aim is to monitor the quality of childhood cancer care in Denmark; to register late effects of treatment; to analyze complications of permanent central venous catheters (CVCs); to study blood stream infections in children with cancer; and to study acute toxicity of high......-dose methotrexate infusions in children with leukemia. STUDY POPULATION: All children below 15 years of age at diagnosis living in Denmark diagnosed after January 1, 1985 according to the International Classification of Diseases 10, including diagnoses DC00-DD48. MAIN VARIABLES: Cancer type, extent of disease......, and outcome of antimicrobial chemotherapy. DESCRIPTIVE DATA: Since 1985, 4,944 children below 15 years of age have been registered in the database. There has been no significant change in the incidence of childhood cancer in Denmark since 1985. The 5-year survival has increased significantly since 1985...

  19. Danish Childhood Cancer Registry

    DEFF Research Database (Denmark)

    Schrøder, Henrik; Rechnitzer, Catherine; Wehner, Peder Skov

    2016-01-01

    AIM OF DATABASE: The overall aim is to monitor the quality of childhood cancer care in Denmark; to register late effects of treatment; to analyze complications of permanent central venous catheters (CVCs); to study blood stream infections in children with cancer; and to study acute toxicity of high......, and outcome of antimicrobial chemotherapy. DESCRIPTIVE DATA: Since 1985, 4,944 children below 15 years of age have been registered in the database. There has been no significant change in the incidence of childhood cancer in Denmark since 1985. The 5-year survival has increased significantly since 1985......-dose methotrexate infusions in children with leukemia. STUDY POPULATION: All children below 15 years of age at diagnosis living in Denmark diagnosed after January 1, 1985 according to the International Classification of Diseases 10, including diagnoses DC00-DD48. MAIN VARIABLES: Cancer type, extent of disease...

  20. Childhood pneumonia and vitamin A

    Directory of Open Access Journals (Sweden)

    Farhad Heidarian

    2014-04-01

    Full Text Available One of the major causes of mortality in children younger than 5 years old is acute lower respiratory tract infections (ALRI. ALRI clinical features are cough, tachypnea, fever, coryza, chest retraction, crackles and wheeze. Increased white blood cell count with left shift might happen in pneumonia. C-reactive protein (CRP and erythrocyte sedimentation rate (ESR might rise in children with respiratory tract infections. Vitamin A deficiency is associated with severe childhood infections. The effect of vitamin A supplementation in childhood pneumonia depends on the prevalence and the level of vitamin A deficiency in the population. Some studies confirmed that retinol levels were significantly higher after recovery from acute pneumonia compared to acute phase. But there were no significant association between serum retinol level and the clinical manifestation.

  1. Outcome After First Relapse in Children With Acute Lymphoblastic Leukemia : A Report Based on the Dutch Childhood Oncology Group (DCOG) Relapse ALL 98 Protocol

    NARCIS (Netherlands)

    van den Berg, H.; de Groot-Kruseman, H. A.; Damen-Korbijn, C. M.; de Bont, E. S. J. M.; Schouten-van Meeteren, A. Y. N.; Hoogerbrugge, P. M.

    Background. We report on the treatment of children and adolescents with acute lymphoblastic leukemia (ALL) in first relapse. The protocol focused on: (1) Intensive chemotherapy preceding allogeneic stem cell transplantation (SCT) in early bone marrow relapse; (2) Rotational chemotherapy in late

  2. Outcome of ETV6/RUNX1-positive childhood acute lymphoblastic leukaemia in the NOPHO-ALL-1992 protocol: frequent late relapses but good overall survival

    DEFF Research Database (Denmark)

    Forestier, E.; Heyman, M.; Andersen, Mette Klarskov

    2008-01-01

    The prognostic impact of t(12;21)(p13;q22) [ETV6/RUNX1 fusion] in paediatric acute lymphoblastic leukaemia (ALL) has been extensively debated, particularly with regard to the frequency of late relapses and appropriate treatment regimens. We have retrospectively collected 679 ALLs with known ETV6/...

  3. The use of the Berlin definition for acute respiratory distress syndrome during infancy and early childhood : multicenter evaluation and expert consensus

    NARCIS (Netherlands)

    De Luca, Daniele; Piastra, Marco; Chidini, Giovanna; Tissieres, Pierre; Calderini, Edoardo; Essouri, Sandrine; Medina Villanueva, Alberto; Vivanco Allende, Ana; Pons-Odena, Marti; Perez-Baena, Luis; Hermon, Michael; Tridente, Ascanio; Conti, Giorgio; Antonelli, Massimo; Kneyber, Martin

    2013-01-01

    A new acute respiratory distress syndrome (ARDS) definition has been recently issued: the so-called Berlin definition (BD) has some characteristics that could make it suitable for pediatrics. The European Society for Pediatric Neonatal Intensive Care (ESPNIC) Respiratory Section started a project to

  4. Intrachromosomal amplification of chromosome 21 (iAMP21 detected by ETV6/RUNX1 FISH screening in childhood acute lymphoblastic leukemia: a case report

    Directory of Open Access Journals (Sweden)

    Daniela Ribeiro Ney Garcia

    2013-01-01

    Full Text Available Chromosome abnormalities that usually define high-risk acute lymphoblastic leukemia are the t(9;22/ breakpoint cluster region protein-Abelson murine leukemia viral oncogene homolog 1, hypodiploid with < 44 chromosomes and 11q23/ myeloid/lymphoid leukemia gene rearrangements. The spectrum of acute lymphoblastic leukemia genetic abnormalities is nevertheless rapidly expanding. Therefore, newly described chromosomal aberrations are likely to have an impact on clinical care in the near future. Recently, the rare intrachromosomal amplification of chromosome 21 started to be considered a high-risk chromosomal abnormality. It occurs in approximately 2-5% of pediatric patients with B-cell precursor acute lymphoblastic leukemia. This abnormality is associated with a poor outcome. Hence, an accurate detection of this abnormality is expected to become very important in the choice of appropriate therapy. In this work the clinical and molecular cytogenetic evaluation by fluorescence in situ hybridization of a child with B-cell precursor acute lymphoblastic leukemia presenting the rare intrachromosomal amplification of chromosome 21 is described.

  5. Intrachromosomal amplification of chromosome 21 (iAMP21) detected by ETV6/RUNX1 FISH screening in childhood acute lymphoblastic leukemia: a case report

    Science.gov (United States)

    Garcia, Daniela Ribeiro Ney; Arancibia, Alejandro Mauricio; Ribeiro, Raul C.; Land, Marcelo Gerardin Poirot; Silva, Maria Luiza Macedo

    2013-01-01

    Chromosome abnormalities that usually define high-risk acute lymphoblastic leukemia are the t(9;22)/ breakpoint cluster region protein-Abelson murine leukemia viral oncogene homolog 1, hypodiploid with < 44 chromosomes and 11q23/ myeloid/lymphoid leukemia gene rearrangements. The spectrum of acute lymphoblastic leukemia genetic abnormalities is nevertheless rapidly expanding. Therefore, newly described chromosomal aberrations are likely to have an impact on clinical care in the near future. Recently, the rare intrachromosomal amplification of chromosome 21 started to be considered a high-risk chromosomal abnormality. It occurs in approximately 2-5% of pediatric patients with B-cell precursor acute lymphoblastic leukemia. This abnormality is associated with a poor outcome. Hence, an accurate detection of this abnormality is expected to become very important in the choice of appropriate therapy. In this work the clinical and molecular cytogenetic evaluation by fluorescence in situ hybridization of a child with B-cell precursor acute lymphoblastic leukemia presenting the rare intrachromosomal amplification of chromosome 21 is described. PMID:24255623

  6. The Prognostic Significance of The Serum Tumor Necrosis Factor (TNF-Related Apoptosis-Inducing Ligand (TRAIL in Childhood Acute Leukemias

    Directory of Open Access Journals (Sweden)

    Zeliha Haytoglu

    2015-12-01

    Results: The comparison of the average values of the TRAIL levels in acute leukemia patients and control group have shown that patients with leukemia have low serum TRAIL levels (p=0.002. In patients with high-risk-grade (HRG of ALL compared with control group have shown low serum TRAIL levels in HRG of ALL (p=0.008. In patients with common acute lymphoblastic leukemia antigen(CALLA(- B ALL compared with control group have shown low serum TRAIL levels in CALLA(- B ALL (p=0.004. Children with acute leukemias (ALL, AML who died during treatment compared with survived group have shown low levels of serum TRAIL in expired patients (p=0.004. Conclusion: As a result, serum TRAIL might play a role in leukomegenesis. The low levels of serum TRAIL detected in our patients may be associated with leukomogenezis and impaired TRAIL-mediated apoptosis. To suggest soluble TRAIL's role in acute leukemias detection of TRAIL-mediated apoptosis is needed. The low serum TRAIL may be used as a sign of bad prognosis. For more comphrensive results prospective studies with greaater number of patients are needed. [Cukurova Med J 2015; 40(4.000: 774-781

  7. Childhood Cancer Statistics

    Science.gov (United States)

    ... Financial Reports Watchdog Ratings Feedback Contact Select Page Childhood Cancer Statistics Home > Cancer Resources > Childhood Cancer Statistics Childhood Cancer Statistics – Graphs and Infographics Number of Diagnoses ...

  8. Frequency of USP6 rearrangements in myositis ossificans, brown tumor, and cherubism: molecular cytogenetic evidence that a subset of "myositis ossificans-like lesions" are the early phases in the formation of soft-tissue aneurysmal bone cyst.

    Science.gov (United States)

    Sukov, William R; Franco, Marcello F; Erickson-Johnson, Michele; Chou, Margaret M; Unni, K Krishnan; Wenger, Doris E; Wang, Xiaoke; Oliveira, Andre M

    2008-04-01

    USP6 rearrangements with several partner genes have been identified recently in primary but not in secondary aneurysmal bone cysts (ABCs). Several lesions show histologic features that may overlap with ABC, including myositis ossificans (MO), brown tumor, and cherubism. The objective of this study was to assess whether these lesions harbored USP6 rearrangements. Twelve patients with classic radiologic and histologic features of MO, 6 with brown tumors, and 5 with cherubism diagnosed at our institution were studied for the presence of USP6 rearrangements using fluorescence in situ hybridization with probes flanking the USP6 locus on chromosome 17p13. In addition, conventional cytogenetic analysis was performed in 2 patients with cherubism. USP6 rearrangements were identified in 2 patients with radiologic and histologic features consistent with MO. None of the patients with brown tumor or cherubism demonstrated USP6 rearrangements. Cytogenetic analysis of the cherubism patients demonstrated normal karyotypes. These findings indicate that a subset of cases with apparent classic histologic and imaging features of MO are rather better classified as being soft-tissue ABC with clonal USP6 rearrangements. In contrast, no USP6 rearrangements were found in patients with cherubism or brown tumor, supporting the prevailing view that these lesions are distinct biologic entities.

  9. Childhood Leukemia

    Science.gov (United States)

    Leukemia is cancer of the white blood cells. It is the most common type of childhood cancer. ... blood cells help your body fight infection. In leukemia, the bone marrow produces abnormal white blood cells. ...

  10. Childhood Schizophrenia

    Science.gov (United States)

    ... of onset presents special challenges for diagnosis, treatment, education, and emotional and social development. Schizophrenia is a chronic condition that requires lifelong treatment. Identifying and starting treatment for childhood schizophrenia ...

  11. A comparison of peripheral blood and buffy coat smear examination for the prediction of bone marrow relapse of acute lymphoblastic leukaemia in childhood.

    OpenAIRE

    Franklin, I M

    1983-01-01

    In an attempt to see if buffy coat smear examination might be an alternative to bone marrow aspiration for predicting relapse, 98 consecutive bone marrow aspirates from 96 children with acute lymphoblastic leukaemia were examined blind with buffy coat and peripheral blood from the same patients. The 28 bone marrow aspirates from children no longer on treatment were all normal, and routine aspirates would appear unjustified in these patients. Eight of the remaining marrows showed relapse, but ...

  12. Sickle cell disease: acute clinical manifestations in early childhood and molecular characteristics in a group of children in Rio de Janeiro

    Science.gov (United States)

    da Silva Filho, Isaac Lima; Ribeiro, Georgina Severo; Moura, Patrícia Gomes; Vechi, Monica Longo; Cavalcante, Andréa Cony; de Andrada-Serpa, Maria José

    2012-01-01

    Objectives To describe clinical events of sickle cell disease and the correlation with β-globin haplotypes and α-thalassemia in under 6-year-old children. Methods A retrospective study was conducted of under 6-year-old children from the neonatal screening program in Rio de Janeiro. Forty-eight male and 48 female children were enrolled in this study, 79 with sickle cell anemia and 17 with hemoglobin SC. The mean age was 29.9 (standard deviation = 20.9) months, 62 (16.2 ± 8.6) were aged between 0-3 years old and 34 (54.9 ± 11.3) were from 3-6 years old. Painful events, acute splenic sequestration, hemolytic crises, hand-foot and acute chest syndromes and infections were evaluated. Results The events were more frequent in under 3-year-old children, 94% of children had at least one episode. Infection was the most common event affecting 88.5% of children. Acute splenic sequestration took place earlier, while painful crises and acute chest syndromes in under 6-year-old children. Thal-α 3.7 was observed in 20.9% of cases. Bantu was the most frequent haplotype found, followed by Benin. No correlation was observed between clinical events and β-globin haplotypes. Children with sickle cell anemia and α-thalassemia have less infectious events. No correlation was found among these polymorphisms and clinical events, however, the majority of children with Bantu/Bantu and without α-thalassemia had more clinical events. PMID:23049419

  13. Acute management of stones

    DEFF Research Database (Denmark)

    Jung, Helene; Osther, Palle J S

    2015-01-01

    INTRODUCTION: Stone management is often conservative due to a high spontaneous stone passage rate or non-symptomatic calyceal stones that do not necessarily require active treatment. However, stone disease may cause symptoms and complications requiring urgent intervention. MATERIAL AND METHODS......: In this review, we update latest research and current recommendations regarding acute management of stones, with particular focus on imaging, pain management, active stone interventions, medical expulsive therapy, and urolithiasis in pregnancy and childhood. RESULTS: Acute stone management should be planned...

  14. Renal, gastrointestinal, and hepatic late effects in survivors of childhood acute myeloid leukemia treated with chemotherapy only--a NOPHO-AML study

    DEFF Research Database (Denmark)

    Skou, Anne-Sofie; Glosli, Heidi; Jahnukainen, Kirsi

    2014-01-01

    of Pediatric Hematology and Oncology (NOPHO). METHODS: A population-based cohort of children treated for AML according to the NOPHO-AML-84, -88, and -93 trials included 138 eligible survivors of whom 102 (74%) completed a questionnaire and 104 (75%) had a clinical examination and blood sampling performed....... Eighty-five of 94 (90%) eligible sibling controls completed a similar questionnaire. Siblings had no clinical examination or blood sampling performed. RESULTS: At a median of 11 years (range 4-25) after diagnosis, renal, gastrointestinal, and hepatic disorders were rare both in survivors of childhood AML...... and in sibling controls, with no significant differences. Ferritin was elevated in 21 (21%) AML survivors but none had biochemical signs of liver damage. Viral hepatitis was present in three and cholelithiasis in two AML survivors. One adult survivor had hypertension, two had slightly elevated systolic blood...

  15. Age at Birth of First Child and Fecundity of Women Survivors of Childhood Acute Lymphoblastic Leukemia (1987-2007): A Study of the Childhood Cancer Registry of the Rhône-Alpes Region in France (ARCERRA).

    Science.gov (United States)

    Freycon, Fernand; Trombert-Paviot, Béatrice; Casagranda, Léonie; Berlier, Pascale; Bertrand, Yves; Plantaz, Dominique; Stephan, Jean-Louis; Berger, Claire

    2015-05-01

    We studied the fecundity of 174 successive ALL (1987-2007) in females of the Childhood Cancer Registry of the Rhône-Alpes Region (ARCERRA) with a median age at follow-up of 25.6 years (18.0-37.4). We distinguished five treatment groups: Group Ia, chemotherapy only (n = 130); Ib, chemotherapy with cranial radiotherapy (n = 10); II, TBI conditioning allograft (n = 27); III, chemotherapy conditioning allograft (n = 4); IV, TBI conditioning autograft (n = 3). Twenty-three women had their first child at the mean age of 25.8 ±3.0 years, i.e., 2.0 ±2.9 years earlier than the general population of the Rhône-Alpes region (P = 0.003). The standardized fertility ratio (SFR), expressed as the number of actual births observed (O) to the number that would be expected in women of the same age in the general population (E) (SFR = O/E) was decreased for Group Ia (0.62; 95%CI, 0.52-0.74) and collapsed in Group II (0.17; 0.11-0.25). In univariate analysis, TBI (P = 0.013) and alkylating agents (P = 0.01) were negatively correlated with fecundity, but not with the age at diagnosis or the anthracyclines doses. In multivariate analysis including TBI and alkylating agents, we still found a negative correlation between TBI (P = 0.035), as well as alkylating agents (P = 0.028), and fecundity. More precisely, fecundity was negatively correlated with cumulative cyclophosphamide equivalent dose (P = 0.001), with a fecundity decreased for ≥1g/m(2), but without any dose effect; results not found in the Group Ia. Age at first child seems younger but the young median age of the cohort not allows concluding; fecundity is collapsed after fractionated total body irradiation and decreased after chemotherapy without any demonstrable cause. A delay of fertility is not excluded.

  16. Sporadic inclusion-body myositis: A degenerative muscle disease associated with aging, impaired muscle protein homeostasis and abnormal mitophagy.

    Science.gov (United States)

    Askanas, Valerie; Engel, W King; Nogalska, Anna

    2015-04-01

    Sporadic inclusion-body myositis (s-IBM) is the most common degenerative muscle disease in which aging appears to be a key risk factor. In this review we focus on several cellular molecular mechanisms responsible for multiprotein aggregation and accumulations within s-IBM muscle fibers, and their possible consequences. Those include mechanisms leading to: a) accumulation in the form of aggregates within the muscle fibers, of several proteins, including amyloid-β42 and its oligomers, and phosphorylated tau in the form of paired helical filaments, and we consider their putative detrimental influence; and b) protein misfolding and aggregation, including evidence of abnormal myoproteostasis, such as increased protein transcription, inadequate protein disposal, and abnormal posttranslational modifications of proteins. Pathogenic importance of our recently demonstrated abnormal mitophagy is also discussed. The intriguing phenotypic similarities between s-IBM muscle fibers and the brains of Alzheimer and Parkinson's disease patients, the two most common neurodegenerative diseases associated with aging, are also discussed. This article is part of a Special Issue entitled: Neuromuscular Diseases: Pathology and Molecular Pathogenesis. Copyright © 2014. Published by Elsevier B.V.

  17. Autoantibodies produced at the site of tissue damage provide evidence of humoral autoimmunity in inclusion body myositis.

    Directory of Open Access Journals (Sweden)

    Arundhati Ray

    Full Text Available Inclusion body myositis (IBM belongs to a group of muscle diseases known as the inflammatory myopathies. The presence of antibody-secreting plasma cells in IBM muscle implicates the humoral immune response in this disease. However, whether the humoral immune response actively contributes to IBM pathology has not been established. We sought to investigate whether the humoral immune response in IBM both in the periphery and at the site of tissue damage was directed towards self-antigens. Peripheral autoantibodies present in IBM serum but not control serum recognized self-antigens in both muscle tissue and human-derived cell lines. To study the humoral immune response at the site of tissue damage in IBM patients, we isolated single plasma cells directly from IBM-derived muscle tissue sections and from these cells, reconstructed a series of recombinant immunoglobulins (rIgG. These rIgG, each representing a single muscle-associated plasma cell, were examined for reactivity to self-antigens. Both, flow cytometry and immunoblotting revealed that these rIgG recognized antigens expressed by cell lines and in muscle tissue homogenates. Using a mass spectrometry-based approach, Desmin, a major intermediate filament protein, expressed abundantly in muscle tissue, was identified as the target of one IBM muscle-derived rIgG. Collectively, these data support the view that IBM includes a humoral immune response in both the periphery and at the site of tissue damage that is directed towards self-antigens.

  18. ZNF384-related fusion genes define a subgroup of childhood B-cell precursor acute lymphoblastic leukemia with a characteristic immunotype.

    Science.gov (United States)

    Hirabayashi, Shinsuke; Ohki, Kentaro; Nakabayashi, Kazuhiko; Ichikawa, Hitoshi; Momozawa, Yukihide; Okamura, Kohji; Yaguchi, Akinori; Terada, Kazuki; Saito, Yuya; Yoshimi, Ai; Ogata-Kawata, Hiroko; Sakamoto, Hiromi; Kato, Motohiro; Fujimura, Junya; Hino, Moeko; Kinoshita, Akitoshi; Kakuda, Harumi; Kurosawa, Hidemitsu; Kato, Keisuke; Kajiwara, Ryosuke; Moriwaki, Koichi; Morimoto, Tsuyoshi; Nakamura, Kozue; Noguchi, Yasushi; Osumi, Tomoo; Sakashita, Kazuo; Takita, Junko; Yuza, Yuki; Matsuda, Koich; Yoshida, Teruhiko; Matsumoto, Kenji; Hata, Kenichiro; Kubo, Michiaki; Matsubara, Yoichi; Fukushima, Takashi; Koh, Katsuyoshi; Manabe, Atsushi; Ohara, Akira; Kiyokawa, Nobutaka

    2017-01-01

    Fusion genes involving ZNF384 have recently been identified in B-cell precursor acute lymphoblastic leukemia, and 7 fusion partners have been reported. We further characterized this type of fusion gene by whole transcriptome sequencing and/or polymerase chain reaction. In addition to previously reported genes, we identified BMP2K as a novel fusion partner for ZNF384 Including the EP300-ZNF384 that we reported recently, the total frequency of ZNF384-related fusion genes was 4.1% in 291 B-cell precursor acute lymphoblastic leukemia patients enrolled in a single clinical trial, and TCF3-ZNF384 was the most recurrent, with a frequency of 2.4%. The characteristic immunophenotype of weak CD10 and aberrant CD13 and/or CD33 expression was revealed to be a common feature of the leukemic cells harboring ZNF384-related fusion genes. The signature gene expression profile in TCF3-ZNF384-positive patients was enriched in hematopoietic stem cell features and related to that of EP300-ZNF384-positive patients, but was significantly distinct from that of TCF3-PBX1-positive and ZNF384-fusion-negative patients. However, clinical features of TCF3-ZNF384-positive patients are markedly different from those of EP300-ZNF384-positive patients, exhibiting higher cell counts and a younger age at presentation. TCF3-ZNF384-positive patients revealed a significantly poorer steroid response and a higher frequency of relapse, and the additional activating mutations in RAS signaling pathway genes were detected by whole exome analysis in some of the cases. Our observations indicate that ZNF384-related fusion genes consist of a distinct subgroup of B-cell precursor acute lymphoblastic leukemia with a characteristic immunophenotype, while the clinical features depend on the functional properties of individual fusion partners. Copyright© Ferrata Storti Foundation.

  19. Myelotoxicity after high-dose methotrexate in childhood acute leukemia is influenced by 6-mercaptopurine dosing but not by intermediate thiopurine methyltransferase activity

    DEFF Research Database (Denmark)

    Levinsen, Mette; Rosthøj, Susanne; Nygaard, Ulrikka

    2015-01-01

    Purpose: Through enhancement of 6-mercaptopurine (6MP) bioavailability and inhibition of purine de novo synthesis, high-dose methotrexate (HD-MTX) may increase incorporation into DNA of 6-thioguanine nucleotides, the cytotoxic metabolites of 6MP. Patients with intermediate activity of thiopurine......,749 HD-MTX courses to 411 children with acute lymphoblastic leukemia on maintenance therapy. Results: The degree of myelosuppression following HD-MTX was similar for patients with TPMTIA and patients with high TPMT activity (TPMTHA), when HD-MTX started with same blood counts and 6MP doses. However...... significantly related to 6MP dose (P activity....

  20. Acute Idiopathic Thrombocytopenic

    OpenAIRE

    Basavaraj Bhagawati; Rahul Hegde

    2003-01-01

    Acute thrombocytopenic purpura is the most common of thrombocytopenias of the childhood. Clinical Features include petechial lesions on oral mucosa, gingival bleeding and occassionally hemorrhage into tissues. Serious complications like intracranial bleeding are also reported. This paper describes a case, presenting in our dental OPD and reviews on published guidelines.