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Sample records for infantile malignant osteopetrosis

  1. Malignant infantile osteopetrosis and primary pulmonary hypertension: a new combination?

    PubMed

    Kasow, Kimberly A; Bonfim, Carmem; Asch, Julie; Margolis, David A; Jenkins, Jesse; Tamburro, Robert F; Handgretinger, Rupert; Horwitz, Edwin M

    2004-02-01

    Malignant infantile osteopetrosis (MIOP), a rare genetic disorder of the osteoclast, is fatal without hematopoietic stem cell transplantation. Primary pulmonary hypertension (PPH), a rare progressive disorder of the pulmonary circulation, is predominantly fatal in the absence of successful therapy. A clinical association between these two disorders has not been recognized and a pathophysiologic link between osteoclast function and pulmonary vascular pressure as a rationale for such an association is not readily apparent. Here, we report five infants with MIOP, without cardiac abnormalities, who were found to have PPH after undergoing stem cell transplantation. We suggest that PPH may be linked to a specific variant of MIOP and recognizing the potential for pulmonary hypertension in children with MIOP may lead to a more rapid diagnosis and life-saving intervention. PMID:14752886

  2. A Histologically Diagnosed Case with Infantile Osteopetrosis Complicated by Hypopituitarism

    PubMed Central

    Diniz, Gulden; Olukman, Ozgur; Calkavur, Sebnem; Buyukinan, Muammer; Altay, Canan

    2015-01-01

    Malignant infantile osteopetrosis is a rarely seen severe disorder which appears early in life with general sclerosis of the skeleton. It is caused by functionally defective osteoclasts which fail to resorb bone. Affected infants can exhibit a wide spectrum of clinical manifestations including impaired hematopoiesis, hepatosplenomegaly, visual impairment, and hypocalcemia. With the exception of secondary hyperparathyroidism, involvement of the endocrine system seems to be quite rare. Hypopituitarism is defined as underproduction of the growth hormone in combination with deficiencies of other pituitary hormones. Any lesion that damages hypothalamus, pituitary stalk, or anterior pituitary can cause secondary hypopituitarism. In this report, we presented a rare combination of malignant infantile osteopetrosis and secondary hypopituitarism in a newborn who presented predominantly with endocrinological symptoms. This is the first case report of malignant infantile osteopetrosis accompanied by hypopituitarism secondary to sclerosis of the sella turcica. On the other hand, this is a very interesting case which was diagnosed based on histological examination of bone marrow biopsy specimens despite lack of any clinical suspicion. PMID:26576309

  3. A novel mutation and a known mutation in the CLCN7 gene associated with relatively stable infantile malignant osteopetrosis in a Chinese patient.

    PubMed

    Zeng, Binghui; Li, Ru; Hu, Yuelin; Hu, Bin; Zhao, Qiang; Liu, Huijiao; Yuan, Ping; Wang, Yiming

    2016-01-15

    Osteopetrosis is a group of heterogeneous disorders caused by the dysfunction of osteoclasts. The CLCN7 and TCIRG1 genes are the major obligate genes responsible for infantile malignant osteopetrosis (IMO). IMO patients usually die in infancy or before three years of age. In this study, we report a patient who was diagnosed with IMO at seven months of age. The patient presented with classical radiological features of IMO. She also exhibited erythropenia, thrombocytopenia, hepatosplenomegaly and neurodegeneration. The parents discontinued any medical treatment for the patient. Surprisingly, the patient's condition did not deteriorate when she was admitted a second time at the age of four years and nine months, despite not receiving any medical support during the untreated period. We sequenced the CLCN7 and TCIRG1 genes of the patient and her parents and identified a novel c.285+1G>A (IVS3+1G>A) mutation and the known c.896C>T (p.Ala299Val) mutation. The novel c.285+1G>A mutation occurred on the splice donor of the third intron of CLCN7. This mutation was predicted to interfere with normal splicing between exons 3 and 4, thereby truncating 711 amino acids from the C terminus and resulting in the loss of all of the functional domains of the encoded protein. The c.896C>T (p.Ala299Val) mutation was a previously known pathogenic mutation. We did not find any pathogenic mutations in the TCIRG1 gene. CLCN7-related osteopetrosis is known to have a high phenotype heterogeneity. Our study demonstrates a wide heterogeneity in the progression of the phenotypes and expanded the mutational spectrum for the CLCN7 gene. PMID:26477479

  4. Hematopoietic stem cell transplantation for infantile osteopetrosis

    PubMed Central

    Fasth, Anders L.; Le Rademacher, Jennifer; He, Wensheng; Boelens, Jaap Jan; Horwitz, Edwin M.; Al-Seraihy, Amal; Ayas, Mouhab; Bonfim, Carmem M.; Boulad, Farid; Lund, Troy; Buchbinder, David K.; Kapoor, Neena; O’Brien, Tracey A.; Perez, Miguel A. Diaz; Veys, Paul A.; Eapen, Mary

    2015-01-01

    We report the international experience in outcomes after related and unrelated hematopoietic transplantation for infantile osteopetrosis in 193 patients. Thirty-four percent of transplants used grafts from HLA-matched siblings, 13% from HLA-mismatched relatives, 12% from HLA-matched, and 41% from HLA-mismatched unrelated donors. The median age at transplantation was 12 months. Busulfan and cyclophosphamide was the most common conditioning regimen. Long-term survival was higher after HLA-matched sibling compared to alternative donor transplantation. There were no differences in survival after HLA-mismatched related, HLA-matched unrelated, or mismatched unrelated donor transplantation. The 5- and 10-year probabilities of survival were 62% and 62% after HLA-matched sibling and 42% and 39% after alternative donor transplantation (P = .01 and P = .002, respectively). Graft failure was the most common cause of death, accounting for 50% of deaths after HLA-matched sibling and 43% of deaths after alternative donor transplantation. The day-28 incidence of neutrophil recovery was 66% after HLA-matched sibling and 61% after alternative donor transplantation (P = .49). The median age of surviving patients is 7 years. Of evaluable surviving patients, 70% are visually impaired; 10% have impaired hearing and gross motor delay. Nevertheless, 65% reported performance scores of 90 or 100, and in 17%, a score of 80 at last contact. Most survivors >5 years are attending mainstream or specialized schools. Rates of veno-occlusive disease and interstitial pneumonitis were high at 20%. Though allogeneic transplantation results in long-term survival with acceptable social function, strategies to lower graft failure and hepatic and pulmonary toxicity are urgently needed. PMID:26012570

  5. Osteopetrosis and Chiari type I malformation: a rare association

    PubMed Central

    Ekici, Mehmet Ali; C?kla, Ula?; Bauer, Andrew; Ba?kaya, Mustafa K.

    2015-01-01

    Osteopetrosis (OP) is hereditary X-linked, autosomal recessive (ARO), or autosomal dominant (ADO) skeletal disease. ARO has two subtypes, which are infantile malignant and intermediate type. ARO and X-linked OP have poor clinical outcome. ADO is called adult benign type because of the normal life expectancy, which has type I and type II. Here, the authors present an ADO patient with Chiari type I. Concomitant ADO with Chiari type I malformation is an extremely rare condition. Literature research yielded only one case report to date. PMID:26503583

  6. Osteopetrosis: genetics, treatment and new insights into osteoclast function.

    PubMed

    Sobacchi, Cristina; Schulz, Ansgar; Coxon, Fraser P; Villa, Anna; Helfrich, Miep H

    2013-09-01

    Osteopetrosis is a genetic condition of increased bone mass, which is caused by defects in osteoclast formation and function. Both autosomal recessive and autosomal dominant forms exist, but this Review focuses on autosomal recessive osteopetrosis (ARO), also known as malignant infantile osteopetrosis. The genetic basis of this disease is now largely uncovered: mutations in TCIRG1, CLCN7, OSTM1, SNX10 and PLEKHM1 lead to osteoclast-rich ARO (in which osteoclasts are abundant but have severely impaired resorptive function), whereas mutations in TNFSF11 and TNFRSF11A lead to osteoclast-poor ARO. In osteoclast-rich ARO, impaired endosomal and lysosomal vesicle trafficking results in defective osteoclast ruffled-border formation and, hence, the inability to resorb bone and mineralized cartilage. ARO presents soon after birth and can be fatal if left untreated. However, the disease is heterogeneous in clinical presentation and often misdiagnosed. This article describes the genetics of ARO and discusses the diagnostic role of next-generation sequencing methods. The management of affected patients, including guidelines for the indication of haematopoietic stem cell transplantation (which can provide a cure for many types of ARO), are outlined. Finally, novel treatments, including preclinical data on in utero stem cell treatment, RANKL replacement therapy and denosumab therapy for hypercalcaemia are also discussed. PMID:23877423

  7. Osteopetrosis: Radiological & Radionuclide Imaging

    PubMed Central

    Sit, Cherry; Agrawal, Kanhaiyalal; Fogelman, Ignac; Gnanasegaran, Gopinath

    2015-01-01

    Osteopetrosis is a rare inherited bone disease where bones harden and become abnormally dense. While the diagnosis is clinical, it also greatly relies on appearance of the skeleton radiographically. X-ray, radionuclide bone scintigraphy and magnetic resonance imaging have been reported to identify characteristics of osteopetrosis. We present an interesting case of a 59-year-old man with a history of bilateral hip fractures. He underwent 99mTc-methylene diphosphonate whole body scan supplemented with single-photon emission computed tomography/computed tomography of spine, which showed increased uptake in the humeri, tibiae and femora, which were in keeping with osteopetrosis. PMID:25589808

  8. Severe neuronopathic autosomal recessive osteopetrosis due to homozygous deletions affecting OSTM1.

    PubMed

    Ott, Claus-Eric; Fischer, Björn; Schröter, Phillipe; Richter, Reyk; Gupta, Neerja; Verma, Nishant; Kabra, Madhulika; Mundlos, Stefan; Rajab, Anna; Neitzel, Heidemarie; Kornak, Uwe

    2013-08-01

    Autosomal recessive osteopetrosis (ARO, MIM 259700) is a genetically heterogeneous rare skeletal disorder characterized by failure of osteoclast resorption leading to pathologically increased bone density, bone marrow failure, and fractures. In the neuronopathic form neurological complications are especially severe and progressive. An early identification of the underlying genetic defect is imperative for assessment of prognosis and treatment by hematopoietic stem cell transplantation. Here we describe for the first time homozygous microdeletions of different sizes affecting the OSTM1 gene in two unrelated consanguineous families with children suffering from neuronopathic infantile malignant osteopetrosis. Patients showed an exceptionally severe phenotype with variable CNS malformations, seizures, blindness, and deafness. Multi-organ failure due to sepsis led to early death between six weeks and five months of age in spite of intensive care treatment. Analysis of the breakpoints revealed different mechanisms underlying both rearrangements. Microdeletions seem to represent a considerable portion of OSTM1 mutations and should therefore be included in a sufficient diagnostic screening. PMID:23685543

  9. 99Tcm-MDP Imaging of Osteopetrosis

    PubMed Central

    Zheng, Li-Chun; OuYang, Xiang-Liu; Liu, Gui-Chao; Zhang, Wen-Jun; Zhang, Xiao-Ming

    2015-01-01

    Abstract Osteopetrosis, also known as marble bone disease, is a clinically rare genetic disease, which represents a heterogeneous group of rare, inherited bone dysplasias that share the hallmark of abnormally increased bone density caused by osteoclast dysfunction. Hereby, the authors describe a case of osteopetrosis that showed increased diffuse radioactive uptake on whole body bone 99Tcm-methylene diphosphonate imaging in a 56-year-old man, which increased universal radioactive uptake on craniofacial bone imaging, and enlargement of the limb long bone near the joints with evenly symmetrical enriched distribution of radioactivity. Osteopetrosis was made which based on these features and characteristics shown on 99Tcm-MDP imaging. Skeletal scintigraphy with 99Tcm-methylene diphosphonate imaging is helpful to the diagnosis of osteopetrosis. There is a characteristic of osteopetrosis different from other bone metabolic diseases. PMID:26039130

  10. HEREDITARY OSTEOPETROSIS OF THE RABBIT

    PubMed Central

    Pearce, Louise; Brown, Wade H.

    1948-01-01

    The manifestations and course of an hereditary disease of the rabbit are reported. The condition is present at birth and is invariably fatal, generally in the 4th and 5th weeks of age. Retardation and eventual cessation of growth with marked reduction in size are conspicuous characteristic symptoms. The condition, which first occurred in the backcross progeny of a pure bred Dutch male rabbit, is inherited. It is determined by the expression of a simple recessive unit factor, affected individuals being homozygous for the factor. Rabbits heterozygous for the factor are identified only by appropriate breeding tests. The condition is not sex-linked. The disease has a remarkable resemblance to osteopetrosis or marble bone disease of infants and children with respect to signs and general course and also, as may be stated in anticipation of later discussions (5, 6), to the characteristic abnormal condition of the skeleton. PMID:18103397

  11. [Cure of osteopetrosis by allogenic bone marrow injection in the double mutant "osteopetrosi-athymic" rat].

    PubMed

    Moutier, R; Toyama, K; Lamendin, H; Ballet, J J

    1979-11-19

    The cure of osteopetrosis by allogenic bone marrow injection has been obtained in homozygous rats for both mutations, osteopetrosis (op) and athymic nude (rnu). This new animal model will help in studying the eventual relationship between the bone resorption process and the immunological reconstitution. PMID:121252

  12. [Osteomyelitis of the jaw and osteopetrosis].

    PubMed

    Khochtali, H; Abassi-Bakir, D; Korbi, S; Ezzeddine, H; Bakir, A

    1991-01-01

    Osteopetrosis (Albers-Schönberg disease) is a rare sclerosing bone disorder in which osteomyelitis of the jaws is a frequent complication. Treatment of osteomyelitis is difficult and may lead to large resection. We report three new cases and we review the literature. PMID:1896806

  13. Osteopetrosis: A New Cause of Upper Gastrointestinal Bleeding.

    PubMed

    Katz, Kristina N; Shafqet, Muhammad A; Rampertab, S Devi; Pooran, Nakechand

    2014-10-01

    Osteopetrosis is a genetic disorder of bone remodeling caused by osteoclast dysfunction. Clinical features include short stature, frequent fractures, and recurrent infections. Abnormal bone obliterates the marrow cavity, resulting pancytopenia and extramedullary hematopoiesis in the liver and spleen. The splenomegaly can lead to left-sided portal hypertension. We report the second case of osteopetrosis-induced portal hypertension and the first case of upper gastrointestinal bleeding in a 52-year-old woman with osteopetrosis. PMID:26157903

  14. Total knee arthroplasty in osteopetrosis using patient-specific instrumentation.

    PubMed

    Mayer, Stephanie W; Hug, Kevin T; Hansen, Benjamin J; Bolognesi, Michael P

    2012-09-01

    Osteopetrosis is an uncommon endocrine disease characterized by defective osteoclast resorption of bones. This causes a hard, sclerotic, and brittle bone throughout the skeleton. Fractures and unforgiving subchondral bone are common in this condition, both of which can lead to osteoarthritis. Total knee arthroplasty is often the treatment of choice but presents challenges due to the hard and sclerotic bone present throughout the metaphysis and diaphysis of the femur and the tibia. We present a case of knee osteoarthritis in a patient with osteopetrosis who underwent total knee arthroplasty using patient-specific instrumentation. This technique eliminates intramedullary alignment and minimizes drilling, reaming, and saw passes, making it attractive in the setting of diseases such as osteopetrosis to decrease operative time and potential complications. PMID:22285231

  15. The failure experience of complex total hip arthroplastyin osteopetrosis: case report and literature review

    PubMed Central

    Dong, Lujue; He, Wei; Huo, Shaochuan; Guo, Cheng; Zhou, Chi; Chen, Qunqun; Tang, Hongyu; Xie, Xinying; Wang, Haibin

    2015-01-01

    There is rare literature elaborating the complex total hip arthroplasty (THA) in patients with osteopetrosis who experienced malunion from femoral neck fracture. We have summarized the failure experience of the complex THA in osteopetrosis. Learned from the resurgery in the case reported by this paper, we recommend to highlight the initial stability of the prosthesis and not to overestimate the potency of fracture healing in the complex THA in osteopetrosis. PMID:26628954

  16. Osteopetrosis: a Case of 'Hostile Chest' Associated with Symptomatic Aortic Valve Stenosis.

    PubMed

    Villa, Emmanuel; Lauria, Giuseppe; Messina, Antonio; Rizzi, Andrea; D'Ambrosio, Angela; Leonzi, Ornella; Sabatini, Tony; Troise, Giovanni

    2015-01-01

    Osteopetrosis is a heterogeneous group of heritable conditions in which there is a defect in bone resorption by osteoclasts. It is associated with an increased skeletal mass due to abnormally dense, but brittle, bones. Osteopetrosis varies greatly in severity, and fracture treatment remains a matter of controversy due to altered responses to fixation and the risk of osteomyelitis. The fate of sternotomy in this condition is unknown, and osteopetrosis could represent a situation of 'hostile chest'. Here, the case is described of a patient with osteopetrosis and concomitant symptomatic aortic valve stenosis and coronary artery disease. PMID:26182630

  17. Cánceres infantiles

    Cancer.gov

    Los cánceres infantiles no siempre se tratan como los cánceres en adultos. La oncología pediátrica es una especialización médica que se concentra en la atención de niños con cáncer. Es importante saber que existen estos conocimientos especializados y que hay tratamientos eficaces para muchos cánceres infantiles.

  18. Early and transient osteopetrosis in microphthalmic MIB-rats.

    PubMed

    Wojtowicz, A; Moutier, R; Grzesik, W; Dziedzic-Goclawska, A; Lamendin, H; Ostrowski, K

    1990-01-01

    Microphtalmic blanc mutation (mib/mib) displays a very mild form of osteopetrosis in rats. The autosomal recessive mib mutation shows pleiotropic expressions in homozygotes. Microphtalmia, absence of eye and skin pigmentation, retardation in the tooth eruption were observed in the mutants. Most bone abnormalities occurred in newborns. An increased radiological opacity of long bones, persistence of primitive bone in medullary cavities, reduced number of poorly differentiated osteoclasts in mandibulae, reduced number of mononuclear peritoneal cells as well as reduced number of mononuclear osteoclast precursors in peritoneal cell population were found. In 3 weeks old and in adult mutants, both bone structure and the number of mandible osteoclasts appear normal, but the number of blood monocytes, peritoneal cells and mononuclear osteoclast precursors in peritoneal cell population remain significantly lower than in the healthy littermates. These observations indicate that the early failure of osteoclast differentiation and maturation is transient in the mib/mib form of osteopetrosis. PMID:2102071

  19. Infantile Esotropia

    MedlinePLUS

    ... delay, intraventricular hemorrhage and a family history of strabismus are among the risk factors for the development ... esotropia treated? Infantile esotropia is usually treated with strabismus surgery (eye muscle surgery). Recently, botulinum toxin has ...

  20. Infantile spasms.

    PubMed

    Hrachovy, Richard A; Frost, James D

    2013-01-01

    Infantile spasms are a unique disorder of infancy and early childhood. The average age at onset of infantile spasms is 6 months and the average incidence of the disorder is approximately 0.31 per 1000 live births. Approximately one-quarter of patients will spontaneously stop having spasms within 1 year of onset. There are three main types of epileptic spasms: flexor, extensor, and mixed flexor-extensor. Spasms frequently occur in clusters and commonly occur upon arousal from sleep. The motor spasms are frequently confused with other normal and abnormal infant behaviors. Typically, the interictal EEG reveals hypsarrhythmia or one of its variants. A variety of ictal EEG patterns may be seen, the most common of which is a generalized slow-wave transient followed by an attenuation of the background activity in all regions. The primary treatment objective is to improve the EEG and stop the spasms as soon as possible and to avoid prolonged treatment durations with any form of therapy. Currently, there is no conclusive evidence that medical or surgical treatment of infantile spasms significantly alters long-term outcome. Although the pathophysiological mechanism underlying infantile spasms is unknown, several animal models of infantile spasms have been developed in recent years. PMID:23622208

  1. Association of possible osteopetrosis with acute myeloid leukaemia in a child

    PubMed Central

    Prasad, Rajniti; Jaiswal, B P; Mishra, O P; Singh, Utpal Kant

    2013-01-01

    Osteopetrosis is a rare disease characterised by an increase in bone mass, skeletal malformations and bone marrow failure due to defective bone resorption. We report a 3-month-old male child presented with chest infections, failure to thrive and hepatosplenomegaly and diagnosed with osteopetrosis associated with acute myeloid leukaemia M3 type (AML-M3). The patient died on day 7 of admission due to respiratory failure. To our knowledge, this is the first case where both osteopetrosis and AML is diagnosed in a patient. PMID:23921696

  2. INFANTILE PARALYSIS

    PubMed Central

    1917-01-01

    At the recent Forty-fourth Annual Meetings of the American Public Health Association, Cincinnati, Ohio, there was held a Round Table Discussion on Infantile Paralysis, in which health authorities throughout the country took part. This discussion was held under the auspices of the Section on Public Health Administration. Dr. George W. Goler, Health Officer of Rochester, N. Y., Chairman of this Section, presided. We take great pleasure in being able to reproduce for readers of the Journal what took place at this most important session. PMID:18009618

  3. A Deletion Mutation in Bovine SLC4A2 is Associated with Osteopetrosis in Red Angus Cattle

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Osteopetrosis is a skeletal disorder characterized by the formation of overly dense bones in affected humans and animals, resulting from a deficiency in the number and/or function of bone-resorbing osteoclast cells. In cattle, osteopetrosis can either be induced during gestation by viral infection ...

  4. Surgical treatment of osteopetrosis-related femoral fractures: two case reports and literature review.

    PubMed

    Aslan, Ahmet; Baykal, Yakup Barbaros; Uysal, Emin; Atay, Tolga; Kirdemir, Vecihi; Baydar, Metin Lütfi; Aydo?an, Nevres Hürriyet

    2014-01-01

    Osteopetrosis is a rare hereditary disease which is characterized by increased bone density. Bone resorption is insufficient or fails due to the osteoclast defect in osteopetrosis. Half of the patients are asymptomatic and diagnosed incidentally or based on the presence of fracture. Adult onset osteopetrosis usually presents with hip and proximal femoral fractures. Internal fixation can be performed; however, technical challenges may be experienced due to increased bone density. As in other fractures, nonunion or varus malunion of these fractures may occur. Although rare, osteopetrosis may complicate treatment of fractures in such patients. In this study, we aimed to present two new cases of ADO type II with an osteopetrotic femoral fracture along with the clinical and radiological findings in the light of a comprehensive literature review. Orthopaedics surgeons should be aware of intraoperative technical difficulties and possible postoperative complications during the follow-up period. Investigation would be beneficial for the diagnosis of osteopetrosis such the patient with fractures who has minor trauma history and increased bone density in radiography. PMID:24579054

  5. Rapid Skeletal Turnover In A Radiographic Mimic Of Osteopetrosis

    PubMed Central

    Whyte, Michael P.; Madson, Katherine L.; Mumm, Steven; McAlister, William H.; Novack, Deborah V.; Blair, Jo C.; Helliwell, Timothy R.; Stolina, Marina; Abernethy, Laurence J.; Shaw, Nicholas J.

    2015-01-01

    Among the high bone mass disorders, the osteopetroses reflect osteoclast failure that prevents skeletal resorption and turnover leading to reduced bone growth and modeling and characteristic histopathological and radiographic findings. We report an 11-year-old boy with a new syndrome that radiographically mimics osteopetrosis but features rapid skeletal turnover. He presented at age 21 months with a parasellar, osteoclast-rich giant cell granuloma. Radiographs showed a dense skull, generalized osteosclerosis, and cortical thickening, medullary cavity narrowing, and diminished modeling of tubular bones. His serum alkaline phosphatase was > 5,000 IU/L (normal < 850). After partial resection, the granuloma re-grew but then regressed and stabilized during three years of uncomplicated pamidronate treatment. His hyperphosphatasemia transiently diminished but all bone turnover markers, especially those of apposition, remained elevated. Two years after pamidronate therapy stopped, BMD z-scores reached + 9.1 and + 5.8 in the lumbar spine and hip, respectively, and iliac crest histopathology confirmed rapid bone remodeling. Serum multiplex biomarker profiling was striking for low sclerostin. Mutation analysis was negative for activation of LRP4, LRP5, or TGF?1 and for defective SOST, OPG, RANKL, RANK, SQSTM1, or sFRP1. Microarray showed no notable copy number variation. Studies of his non-consanguineous parents were unremarkable. The etiology and pathogenesis of this unique syndrome are unknown. PMID:24919763

  6. Osteopetrosis and Its Relevance for the Discovery of New Functions Associated with the Skeleton

    PubMed Central

    Coudert, Amélie E.; de Vernejoul, Marie-Christine; Muraca, Maurizio

    2015-01-01

    Osteopetrosis is a rare genetic disorder characterized by an increase of bone mass due to defective osteoclast function. Patients typically displayed spontaneous fractures, anemia, and in the most severe forms hepatosplenomegaly and compression of cranial facial nerves leading to deafness and blindness. Osteopetrosis comprises a heterogeneous group of diseases as several forms are known with different models of inheritance and severity from asymptomatic to lethal. This review summarizes the genetic and clinical features of osteopetrosis, emphasizing how recent studies of this disease have contributed to understanding the central role of the skeleton in the whole body physiology. In particular, the interplay of bone with the stomach, insulin metabolism, male fertility, the immune system, bone marrow, and fat is described. PMID:25873953

  7. [Cure of osteopetrosis by injection of allogenic bone marrow into "op" rats treated with cyclosporin A].

    PubMed

    Moutier, R; Toyama, K; Lamendin, H

    1985-01-01

    The cure of osteopetrosis by allogenic bone marrow injection has been obtained in "op" mutant rat kept under cyclosporin A treatment. This immunosuppressive agent able to prevent the rejection of transplanted cells does not impair the propriety of these cells to restore the bone resorption process in this severe osteopetrotic form. PMID:3937567

  8. MT2013-31: Allo HCT for Metabolic Disorders and Severe Osteopetrosis

    ClinicalTrials.gov

    2015-06-19

    Mucopolysaccharidosis I; Mucopolysaccharidosis II; Mucopolysaccharidosis VI; Mucopolysaccharidosis VII; Hurler Syndrome; Hunter Syndrome; Maroteaux Lamy Syndrome; Sly Syndrome; Glycoprotein Metabolic Disorders; Alpha Mannosidosis; Fucosidosis; Aspartylglucosaminuria; Adrenoleukodystrophy; Peroxisomal Disorders; Osteopetrosis; Sphingolipidosis; Gangliosidosis; Globoid Cell Leukodystrophy; Metachromatic Leukodystrophy; Niemann Pick B; Niemann Pick C Subtype 2; I-cell Disease

  9. A case of cavernous sinus thrombophlebitis and meningitis as a complication in osteopetrosis.

    PubMed

    Chung, Hyun Chul; Park, So Hyun; Kim, Eun Sook; Kim, Young Il; Lee, Sun Ho; Nam-Goong, Il Seong

    2014-08-01

    Osteopetrosis is a rare genetic bone disease characterized by increased bone density but prone to breakage due to defective osteoclastic function. Among two primary types of autosomal dominant osteopetrosis (ADO), osteopetrosis type II is characterized by sclerosis of bones, predominantly involving the spine, the pelvis, and the skull base. Fragility of bones and dental abscess are leading complications. This report presents a case of osteopetrosis in a 52-years-old female, which was complicated by the development of cavernous sinus thrombophlebitis and meningitis. She was suffered from multiple fractures since one year ago. Laboratory data revealed elevated serum levels of tartrate resistant acid phosphatase (TRAP) without carbonic anhydrase II DNA mutation. A thoracolumbar spine X-ray showed, typical findings of ADO type II (ADO II; Albers-Schönberg disease), prominent vertebral endplates so called the 'rugger jersey spine'. Her older sister also showed same typical spine appearance. We report a case of ADO II with cavernous sinus thrombophlebitis and meningitis that was successfully treated with long-term antibiotics with right sphenoidotomy. PMID:25247162

  10. Treatment of infantile hemangiomas.

    PubMed

    Lauren, Christine; Garzon, Maria C

    2012-08-01

    1.Recognize infantile hemangiomas that are associated with a higher risk for complications and associated anomalies.2.Appreciate the typical timing of growth and involution of infantile hemangiomas.3.Become familiar with recently reported treatments for infantile hemangiomas.Infantile hemangiomas are common proliferations of endothelial tissue that affect approximately 4% to 5% of infants.1 Lesions represent a broad clinical spectrum and their management has to be individualized. Fortunately, most infantile hemangiomas do not require active therapy and may be managed with "active nonintervention";2 however, it is important to recognize those that do require therapeutic intervention and to be familiar with the therapeutic options. PMID:22881415

  11. Osteopetrosis-associated osteomyelitis of the jaws: a report of 4 cases.

    PubMed

    Krithika, Chandrasekaran; Neelakandan, Ravanasamudram Sundaram; Sivapathasundaram, Balasundaram; Koteeswaran, Domadula; Rajaram, Pommai Chinnaiah; Shetkar, Girish Subhash

    2009-09-01

    Osteopetrosis represents a heterogeneous group of rare, hereditary bone disorders with variable clinical features and an increase in bone density. The common clinical findings that usually lead to the detection of the disease are fractures and osteomyelitis of the mandible. We report 4 cases of osteopetrosis, complicated by osteomyelitis of the jaws. Maxillary bone was involved in 3 of the cases and mandible in 1 of the cases. Osteomyelitis of the maxilla is extremely rare. When it occurs, there is invariably an underlying predisposing condition. All the 4 patients presented with osteomyelitis after dental extraction. Skeletal survey revealed multiple healed fractures of the long bones in all the cases. Two patients presented with myelophthisic anemia and evidence of extraosseous hematopoiesis and 1 patient with osteopetrotic stenosis of optic and auditory nerve exit foramina. All 4 cases were treated with intravenous antibiotic therapy and debridement of necrotic bone. PMID:19716493

  12. Bone growth causing ventriculoperitoneal shunt malfunction in a patient with osteopetrosis. Case report.

    PubMed

    Grossman, Rachel; Feldman, Zeev

    2004-05-01

    Osteopetrosis is an inherited skeletal condition of defective osteoclastic resorption of bone resulting in increased bone density. Osseous changes occur most severely at the base of the skull. Important clinical symptoms include cranial nerve palsies due to uni- or bilateral obliteration of cranial nerve foramina including deafness, facial paralysis, and optic nerve compression. Thickening of the skull and progressive diminution of the cranial capacity may lead to elevation of intracranial pressure, papilledema, and hydrocephalus. The authors present an unusual case of a patient with osteopetrosis in whom a ventriculoperitoneal shunt became obstructed at its exit from the skull by the developing bone mass. To the best of their knowledge, this has not been described. PMID:15287468

  13. Genetics Home Reference: Infantile neuronal ceroid lipofuscinosis

    MedlinePLUS

    ... infantile neuronal ceroid lipofuscinosis? Infantile neuronal ceroid lipofuscinosis (NCL) is an inherited disorder that primarily affects the ... characteristic features of this disorder. Children with infantile NCL usually do not survive past childhood. Infantile NCL ...

  14. Propranolol (Infantile Hemangioma)

    MedlinePLUS

    Propranolol oral solution is used to treat proliferating infantile hemangioma (benign [noncancerous] growths or tumors appearing on ... infants 5 weeks to 5 months of age. Propranolol is in a class of medications called beta ...

  15. Persistent viral DNA synthesis associated with an avian osteopetrosis-inducing virus.

    PubMed

    Aurigemma, R E; Comstock, R D; Smith, R E

    1989-08-01

    Bone and red blood cell DNA was obtained from MAV-2(O) infected, osteopetrotic chickens and analyzed for the presence of integrated and unintegrated viral DNA. Results indicate that unintegrated MAV-2(O) DNA did not appear until after osteopetrotic lesions were well established. These observations lead us to conclude that, unlike some retroviral diseases, unintegrated viral DNA may not play a significant role in the pathogenesis of MAV-2(O) osteopetrosis. In addition, there was no evidence of a clonally derived tumor in the bone. PMID:2548335

  16. RANK-dependent autosomal recessive osteopetrosis: characterization of five new cases with novel mutations.

    PubMed

    Pangrazio, Alessandra; Cassani, Barbara; Guerrini, Matteo M; Crockett, Julie C; Marrella, Veronica; Zammataro, Luca; Strina, Dario; Schulz, Ansgar; Schlack, Claire; Kornak, Uwe; Mellis, David J; Duthie, Angela; Helfrich, Miep H; Durandy, Anne; Moshous, Despina; Vellodi, Ashok; Chiesa, Robert; Veys, Paul; Lo Iacono, Nadia; Vezzoni, Paolo; Fischer, Alain; Villa, Anna; Sobacchi, Cristina

    2012-02-01

    Autosomal recessive osteopetrosis (ARO) is a genetically heterogeneous disorder attributed to reduced bone resorption by osteoclasts. Most human AROs are classified as osteoclast rich, but recently two subsets of osteoclast-poor ARO have been recognized as caused by defects in either TNFSF11 or TNFRSF11A genes, coding the RANKL and RANK proteins, respectively. The RANKL/RANK axis drives osteoclast differentiation and also plays a role in the immune system. In fact, we have recently reported that mutations in the TNFRSF11A gene lead to osteoclast-poor osteopetrosis associated with hypogammaglobulinemia. Here we present the characterization of five additional unpublished patients from four unrelated families in which we found five novel mutations in the TNFRSF11A gene, including two missense and two nonsense mutations and a single-nucleotide insertion. Immunological investigation in three of them showed that the previously described defect in the B cell compartment was present only in some patients and that its severity seemed to increase with age and the progression of the disease. HSCT performed in all five patients almost completely cured the disease even when carried out in late infancy. Hypercalcemia was the most important posttransplant complication. Overall, our results further underline the heterogeneity of human ARO also deriving from the interplay between bone and the immune system, and highlight the prognostic and therapeutic implications of the molecular diagnosis. PMID:22271396

  17. Targeted disruption of the Cl?/HCO3? exchanger Ae2 results in osteopetrosis in mice

    PubMed Central

    Josephsen, Kaj; Praetorius, Jeppe; Frische, Sebastian; Gawenis, Lara R.; Kwon, Tae-Hwan; Agre, Peter; Nielsen, Søren; Fejerskov, Ole

    2009-01-01

    Osteoclasts are multinucleated bone-resorbing cells responsible for constant remodeling of bone tissue and for maintaining calcium homeostasis. The osteoclast creates an enclosed space, a lacuna, between their ruffled border membrane and the mineralized bone. They extrude H+ and Cl? into these lacunae by the combined action of vesicular H+-ATPases and ClC-7 exchangers to dissolve the hydroxyapatite of bone matrix. Along with intracellular production of H+ and HCO3? by carbonic anhydrase II, the H+-ATPases and ClC-7 exchangers seems prerequisite for bone resorption, because genetic disruption of either of these proteins leads to osteopetrosis. We aimed to complete the molecular model for lacunar acidification, hypothesizing that a HCO3? extruding and Cl? loading anion exchange protein (Ae) would be necessary to sustain bone resorption. The Ae proteins can provide both intracellular pH neutrality and serve as cellular entry mechanism for Cl? during bone resorption. Immunohistochemistry revealed that Ae2 is exclusively expressed at the contra-lacunar plasma membrane domain of mouse osteoclast. Severe osteopetrosis was encountered in Ae2 knockout (Ae2?/?) mice where the skeletal development was impaired with a higher diffuse radio-density on x-ray examination and the bone marrow cavity was occupied by irregular bone speculae. Furthermore, osteoclasts in Ae2?/? mice were dramatically enlarged and fail to form the normal ruffled border facing the lacunae. Thus, Ae2 is likely to be an essential component of the bone resorption mechanism in osteoclasts. PMID:19164575

  18. Infantile tumoral calcinosis of the cervical spine presenting as torticollis.

    PubMed

    Ashraf, Ali; Diehn, Felix E; Luetmer, Patrick H; Lane, John I; Fritchie, Karen; Larson, A Noelle

    2016-01-01

    The computed tomography (CT) and MRI findings of infantile tumoral calcinosis and the utility of image-guided biopsy are demonstrated. A 5-month old presented with torticollis and a calcified cervical spinal mass. The radiologic appearance suggested a malignant neoplasm, prompting CT-guided biopsy, which diagnosed tumoral calcinosis. We hope to increase awareness of this entity and describe image-guided biopsy as a way to avoid morbidity associated with open biopsy. PMID:26520701

  19. Bone mineral density and laboratory evaluation of a type II autosomal dominant osteopetrosis carrier.

    PubMed

    Takacs, I; Cooper, H; Weaver, D D; Econs, M J

    1999-07-01

    Type II autosomal dominant osteopetrosis (ADO2) is an inherited disorder characterized by increased skeletal mass and characteristic abnormalities evident on radiography. Although previous investigators have described nonpenetrant individuals (carriers), it is not known whether carriers manifest subtle abnormalities. We hypothesized that ADO2 carriers would have an abnormality of osteoclast function that would lead to changes in bone mineral density (BMD), in serum tartrate-resistant acid phosphatase (TRAP), or in creatine kinase isoenzyme BB (CK-BB) levels that would permit carrier recognition. We identified a female carrier in a well-established ADO2 family and measured BMD, serum TRAP, and CK-BB concentrations. She had normal BMD, serum TRAP, and CK-BB concentrations. Thus, these measurements cannot be used to exclude carrier status in individuals who are seen for genetic counseling. However, measurements in other asymptotic carriers are necessary before concluding that these measurements are normal in all or most nonpenetrant individuals. PMID:10377007

  20. Malignant epignathus.

    PubMed

    Rayudu, Harijan Hanumantha; Reddy, Kilashnath; Lakshmi, Kasa; Varma, Santhosh

    2011-07-01

    Report of a neonate with a huge mass protruding from the oral cavity. The mass has originated from the base of the tongue. Successful excision and histopathological examination revealed it to be a malignant epignathus. PMID:21897571

  1. An adult osteopetrosis model in medaka reveals the importance of osteoclast function for bone remodeling in teleost fish.

    PubMed

    To, Thuy Thanh; Witten, Paul Eckhard; Huysseune, Ann; Winkler, Christoph

    2015-12-01

    Osteoclasts play important roles during bone growth and in maintaining bone health and bone homeostasis. Dysfunction or lack of osteoclasts leads to increased bone mass and osteopetrosis phenotypes in mouse and human. Here we report a severe osteopetrosis-like phenotype in transgenic medaka fish, in which membrane bound EGFP (mEGFP) was expressed in osteoclasts under control of the cathepsin K promoter (ctsk:mEGFP). In contrast to reporter lines with GFP expression in the cytoplasm of osteoclasts, adult fish of the mEGFP line developed bone defects indicative for an osteoclast dysfunction. Activity of tartrate-resistant acid phosphatase (TRAP) was down-regulated and excess bone was observed in most parts of the skeleton. The osteopetrotic phenotype was particularly obvious at the neural and haemal arches that failed to increase their volume in growing fish. Excess bone caused severe constriction of the spinal cord and the ventral aorta. The continuation of tooth development and the failure to shed teeth resulted in severe hyperdontia. Interestingly, at the vertebral column vertebral body arches displayed a severe osteopetrosis, while vertebral centra had no or only a mild osteopetrotic phenotype. This confirms previous reports from cichlids that, different from the arches, allometric growth of fish vertebral centra initially does not depend on the action of osteoclasts. Independent developmental mechanism that shapes arches and vertebral centra can also lend support to the hypothesis that vertebral centra and arches function as independent developmental modules. Together, this medaka osteopetrosis model confirms the importance of proper osteoclast function during normal skeletal development in teleost fish that requires bone modeling and remodeling. PMID:26334373

  2. Infantile spasms and HLA antigens.

    PubMed Central

    Howitz, P; Platz, P

    1978-01-01

    21 new cases of infantile spasms were reported in 1976 from paediatric departments in Denmark. The connection between infantile spasms and the Lennox-Gastaut syndrome is mentioned, because of reports of a significantly higher incidence of HLA-B7 in children with Lennox-Gastaut syndrome. The HLA antigen distribution in 19 of the 21 children was compared with that of 1967 healthy adults. No difference in the HLA antigens was demonstrated between children with infantile spasms and controls, whether in the material as a whole, or in the cryptogenic or symptomatic groups. However HLA typing of children with infantile spasms should continue in the search for a potential genetic marker in this grave disease, particularly in view of the reported high incidence of HLA-B7 in children with the Lennox-Gastaut syndrome. PMID:708109

  3. Instantánea de los cánceres infantiles

    Cancer.gov

    Información sobre la incidencia y mortalidad del cáncer en los niños, tendencias en el financiamiento del NCI para la investigación del cáncer infantil; así como ejemplos de actividades y adelantos en la investigación relevantes para esta población.

  4. Genitourinary Malignancies

    PubMed Central

    Connolly, John G.

    1975-01-01

    Early diagnosis of malignant disease in the genitourinary system means a better opportunity for cure. The family physician must be aware of the signs and symptoms of GU tumors in all stages, and the investigations required to establish a diagnosis. In this article the symptomatology, investigative procedures and available treatment options are presented. Carcinoma of the scrotum and penis are not included because they are relatively uncomplicated diagnostic problems. ImagesFig. 1Fig. 3Fig. 4Fig. 5Fig. 6 PMID:20469262

  5. Infantile spasms--evidence based medical management.

    PubMed

    Sahu, Jitendra Kumar

    2014-10-01

    Infantile spasms constitute significant burden of refractory epilepsy in children. The first line treatment choice varies at different centres. The author presents concise evidence based update on medical management of infantile spasms. PMID:24986193

  6. Modeling new therapies for infantile spasms

    PubMed Central

    Chudomelova, Lenka; Scantlebury, Morris H.; Raffo, Emmanuel; Coppola, Antonietta; Betancourth, David; Galanopoulou, Aristea S.

    2010-01-01

    Summary Infantile spasms are the classical seizure type of West syndrome. Infantile spasms often herald a dismal prognosis, due to the high probability to evolve into intractable forms of epilepsies with significant cognitive deficits, especially if not adequately treated. The current therapies, high doses of adrenocorticotropic hormone, steroids or the GABA transaminase inhibitor vigabatrin, are often toxic and may not always be effective. The need to identify new therapies for spasms has led to the generation of a number of rodent models of infantile spasms. These include acute and chronic models of infantile spasms, with cryptogenic or symptomatic origin, many of which are based on specific etiologies. In this review, we will summarize the clinical experience with treating infantile spasms, the main features of the new animal models of infantile spasms and discuss their utility in the preclinical development of new therapies for infantile spasms. PMID:20618396

  7. Elevated serum levels of creatine kinase BB in autosomal dominant osteopetrosis type II--a family study.

    PubMed

    Yoneyama, T; Fowler, H L; Pendleton, J W; Sforza, P P; Gerard, R D; Lui, C Y; Eldridge, T H; Iranmanesh, A

    1992-07-01

    A markedly elevated BB isoenzyme fraction of serum creatine kinase was noted in four male siblings and correlated with typical radiographic findings of autosomal dominant osteopetrosis Type II (ADO Type II). Patients with other sclerosing bone diseases had no elevation of CK-BB. The precision of the electrophoretic mobility patterns and correlation by I-125 tagged radioimmunoassay method confirms that this is CK-BB. We postulate that the dysfunctional and/or immature osteoclasts in ADO are more dependent on CK-BB than on the usual tricarboxylic acid cycle for the production of energy. The correlation of marked elevation of serum CK-BB with radiographic evidence of ADO Type II may prove to be of value as a biologic marker in the early diagnosis of the illness and lead to better understanding of the metabolism of bone. PMID:1516225

  8. Genetics Home Reference: X-linked infantile spasm syndrome

    MedlinePLUS

    ... literature OMIM Genetic disorder catalog Conditions > X-linked infantile spasm syndrome On this page: Description Genetic changes Inheritance ... definitions Reviewed August 2012 What is X-linked infantile spasm syndrome? X-linked infantile spasm syndrome is a ...

  9. Malignant hyperthermia

    PubMed Central

    Rosenberg, Henry; Davis, Mark; James, Danielle; Pollock, Neil; Stowell, Kathryn

    2007-01-01

    Malignant hyperthermia (MH) is a pharmacogenetic disorder of skeletal muscle that presents as a hypermetabolic response to potent volatile anesthetic gases such as halothane, sevoflurane, desflurane and the depolarizing muscle relaxant succinylcholine, and rarely, in humans, to stresses such as vigorous exercise and heat. The incidence of MH reactions ranges from 1:5,000 to 1:50,000–100,000 anesthesias. However, the prevalence of the genetic abnormalities may be as great as one in 3,000 individuals. MH affects humans, certain pig breeds, dogs, horses, and probably other animals. The classic signs of MH include hyperthermia to marked degree, tachycardia, tachypnea, increased carbon dioxide production, increased oxygen consumption, acidosis, muscle rigidity, and rhabdomyolysis, all related to a hypermetabolic response. The syndrome is likely to be fatal if untreated. Early recognition of the signs of MH, specifically elevation of end-expired carbon dioxide, provides the clinical diagnostic clues. In humans the syndrome is inherited in autosomal dominant pattern, while in pigs in autosomal recessive. The pathophysiologic changes of MH are due to uncontrolled rise of myoplasmic calcium, which activates biochemical processes related to muscle activation. Due to ATP depletion, the muscle membrane integrity is compromised leading to hyperkalemia and rhabdomyolysis. In most cases, the syndrome is caused by a defect in the ryanodine receptor. Over 90 mutations have been identified in the RYR-1 gene located on chromosome 19q13.1, and at least 25 are causal for MH. Diagnostic testing relies on assessing the in vitro contracture response of biopsied muscle to halothane, caffeine, and other drugs. Elucidation of the genetic changes has led to the introduction, on a limited basis so far, of genetic testing for susceptibility to MH. As the sensitivity of genetic testing increases, molecular genetics will be used for identifying those at risk with greater frequency. Dantrolene sodium is a specific antagonist of the pathophysiologic changes of MH and should be available wherever general anesthesia is administered. Thanks to the dramatic progress in understanding the clinical manifestation and pathophysiology of the syndrome, the mortality from MH has dropped from over 80% thirty years ago to less than 5%. PMID:17456235

  10. Infantile colic, facts and fiction

    PubMed Central

    2012-01-01

    Infantile colic is one of the major challenges of parenthood. It is one of the common reasons parents seek medical advice during their child’s first 3?months of life. It is defined as paroxysms of crying lasting more than 3 hours a day, occurring more than 3?days in any week for 3?weeks in a healthy baby aged 2?weeks to 4?months. Colic is a poorly understood phenomenon affecting up to 30% of babies, underlying organic causes of excessive crying account for less than 5%. Laboratory tests and radiological examinations are unnecessary if the infant is gaining weight normally and has a normal physical examination. Treatment is limited and drug treatment has no role in management. Probiotics are now emerging as promising agents in the treatment of infantile colic. Alternative medicine (Herbal tea, fennel, glucose and massage therapy) have not proved to be consistently helpful and some might even be dangerous. In conclusion infantile colic is a common cause of maternal distress and family disturbance, the cornerstone of management remains reassurance of parents regarding the benign and self-limiting nature of the illness. There is a critical need for more evidence based treatment protocols. PMID:22823993

  11. Stages of Malignant Mesothelioma

    MedlinePLUS

    ... Malignant mesothelioma is a disease in which malignant (cancer) cells form in the lining of the chest or ... diagnosed, tests are done to find out if cancer cells have spread to other parts of the body. ...

  12. Pediatric Salivary Gland Malignancies.

    PubMed

    Ord, Robert A; Carlson, Eric R

    2016-02-01

    Pediatric malignant salivary gland tumors are extremely rare. The percentage of malignant tumors is higher than that seen in adults, although the outcomes in terms of survival are better in pediatric patients. The mainstay of treatment is surgical excision with negative margins. This article reviews current concepts in demographics, etiology, management, and outcomes of malignant salivary tumors in children. PMID:26614703

  13. Practice Parameter: Medical Treatment of Infantile Spasms

    PubMed Central

    Mackay, M.T.; Weiss, S.K.; Adams-Webber, T.; Ashwal, S.; Stephens, D.; Ballaban-Gill, K.; Baram, T.Z.; Duchowny, M.; Hirtz, D.; Pellock, J.M.; Shields, W.D.; Shinnar, S.; Wyllie, E.; Snead, O.C.

    2010-01-01

    Objective To determine the current best practice for treatment of infantile spasms in children. Methods Database searches of MEDLINE from 1966 and EMBASE from 1980 and searches of reference lists of retrieved articles were performed. Inclusion criteria were the documented presence of infantile spasms and hypsarrhythmia. Outcome measures included complete cessation of spasms, resolution of hypsarrhythmia, relapse rate, developmental outcome, and presence or absence of epilepsy or an epileptiform EEG. One hundred fifty-nine articles were selected for detailed review. Recommendations were based on a four-tiered classification scheme. Results Adrenocorticotropic hormone (ACTH) is probably effective for the short-term treatment of infantile spasms, but there is insufficient evidence to recommend the optimum dosage and duration of treatment. There is insufficient evidence to determine whether oral corticosteroids are effective. Vigabatrin is possibly effective for the short-term treatment of infantile spasm and is possibly also effective for children with tuberous sclerosis. Concerns about retinal toxicity suggest that serial ophthalmologic screening is required in patients on vigabatrin; however, the data are insufficient to make recommendations regarding the frequency or type of screening. There is insufficient evidence to recommend any other treatment of infantile spasms. There is insufficient evidence to conclude that successful treatment of infantile spasms improves the long-term prognosis. Conclusions ACTH is probably an effective agent in the short-term treatment of infantile spasms. Vigabatrin is possibly effective. PMID:15159460

  14. Infantile Colic: Recognition and Treatment.

    PubMed

    Johnson, Jeremy D; Cocker, Katherine; Chang, Elisabeth

    2015-10-01

    Infantile colic is a benign process in which an infant has paroxysms of inconsolable crying for more than three hours per day, more than three days per week, for longer than three weeks. It affects approximately 10% to 40% of infants worldwide and peaks at around six weeks of age, with symptoms resolving by three to six months of age. The incidence is equal between sexes, and there is no correlation with type of feeding (breast vs. bottle), gestational age, or socioeconomic status. The cause of infantile colic is not known; proposed causes include alterations in fecal microflora, intolerance to cow's milk protein or lactose, gastrointestinal immaturity or inflammation, increased serotonin secretion, poor feeding technique, and maternal smoking or nicotine replacement therapy. Colic is a diagnosis of exclusion after a detailed history and physical examination have ruled out concerning causes. Parental support and reassurance are key components of the management of colic. Simethicone and proton pump inhibitors are ineffective for the treatment of colic, and dicyclomine is contraindicated. Treatment options for breastfed infants include the probiotic Lactobacillus reuteri (strain DSM 17938) and reducing maternal dietary allergen intake. Switching to a hydrolyzed formula is an option for formula-fed infants. Evidence does not support chiropractic or osteopathic manipulation, infant massage, swaddling, acupuncture, or herbal supplements. PMID:26447441

  15. Refined genomic localization of the genetic lesion in the osteopetrosis (op) rat and exclusion of three positional and functional candidate genes, Clcn7, Atp6v0c, and Slc9a3r2.

    PubMed

    Perdu, B; Odgren, P R; Van Wesenbeeck, L; Jennes, K; Mackay, C C; Van Hul, W

    2009-05-01

    Osteopetrosis is a disease characterised by a generalized skeletal sclerosis resulting from a reduced osteoclast-mediated bone resorption. Several spontaneous mutations lead to osteopetrotic phenotypes in animals. Moutier et al. (1974) discovered the osteopetrosis (op) rat as a spontaneous, lethal, autosomal recessive mutant. op rats have large nonfunctioning osteoclasts and severe osteopetrosis. Dobbins et al. (2002) localized the disease-causing gene to a 1.5-cM genetic interval on rat chromosome 10, which we confirm in the present report. We also refined the genomic localization of the disease gene and provide statistical evidence for a disease-causing gene in a small region of rat chromosome 10. Three strong functional candidate genes are within the delineated region. Clcn7 was previously shown to underlie different forms of osteopetrosis, in both human and mice. ATP6v0c encodes a subunit of the vacuolar H(+)-ATPase or proton pump. Mutations in TCIRG1, another subunit of the proton pump, are known to cause a severe form of osteopetrosis. Given the critical role of proton pumping in bone resorption, the Slc9a3r2 gene, a sodium/hydrogen exchanger, was also considered as a candidate for the op mutation. RT-PCR showed that all 3 genes are expressed in osteoclasts, but sequencing found no mutations either in the coding regions or in intron splice junctions. Our ongoing mutation analysis of other genes in the candidate region will lead to the discovery of a novel osteopetrosis gene and further insights into osteoclast functioning. PMID:19259722

  16. Familial malignant melanoma

    SciTech Connect

    Kopf, A.W.; Hellman, L.J.; Rogers, G.S.; Gross, D.F.; Rigel, D.S.; Friedman, R.J.; Levenstein, M.; Brown, J.; Golomb, F.M.; Roses, D.F.; Gumport, S.L.

    1986-10-10

    Characteristics associated with familial compared with nonfamilial malignant melanoma were assessed. These data were obtained from consecutive prospectively completed questionnaires on 1169 cases of cutaneous malignant melanoma. Of these, 69 patients indicated a positive family history for this cancer. Among the various clinical and histological variables compared, those that significantly correlated with the familial occurrence of malignant melanoma include younger age at first diagnosis, smaller diameter of the lesion, lower Clark level, decreased frequency of nonmelanoma skin cancer, and reduced prevalence of noncutaneous cancer. Increased awareness of malignant melanoma among family members could account for some of these observations. Identification of the familial variety of malignant melanoma has practical implications concerning early detection and prompt intervention.

  17. Considerations for the Treatment of Infantile Neuronal Ceroid Lipofuscinosis (Infantile Batten Disease)

    PubMed Central

    Sands, Mark S.

    2014-01-01

    The infantile form of neuronal ceroid lipofuscinosis (ie, infantile Batten disease) is the most rapidly progressing type and is caused by an inherited deficiency in the lysosomal enzyme palmitoyl protein thioesterase 1. The absence of enzyme activity leads to progressive accumulation of autofluorescent material in many cell types, particularly neurons of the central nervous system. Clinical signs of infantile neuronal ceroid lipofuscinosis appear between 6 months and 1 year of age and include vision loss, cognitive decline, motor deficits, seizures, and premature death, typically by 3 to 5 years of age. There is currently no effective treatment. However, preclinical experiments in the murine model of infantile neuronal ceroid lipofuscinosis have shown that gene therapy, enzyme replacement, stem cell transplantation, and small molecule drugs, alone or in combination, can significantly slow disease progression. A more thorough understanding of the underlying pathogenesis of infantile neuronal ceroid lipofuscinosis will identify new therapeutic targets. PMID:24014510

  18. A missense mutation accelerating the gating of the lysosomal Cl?/H+-exchanger ClC-7/Ostm1 causes osteopetrosis with gingival hamartomas in cattle

    PubMed Central

    Sartelet, Arnaud; Stauber, Tobias; Coppieters, Wouter; Ludwig, Carmen F.; Fasquelle, Corinne; Druet, Tom; Zhang, Zhiyan; Ahariz, Naima; Cambisano, Nadine; Jentsch, Thomas J.; Charlier, Carole

    2014-01-01

    Chloride-proton exchange by the lysosomal anion transporter ClC-7/Ostm1 is of pivotal importance for the physiology of lysosomes and bone resorption. Mice lacking either ClC-7 or Ostm1 develop a lysosomal storage disease and mutations in either protein have been found to underlie osteopetrosis in mice and humans. Some human disease-causing CLCN7 mutations accelerate the usually slow voltage-dependent gating of ClC-7/Ostm1. However, it has remained unclear whether the fastened kinetics is indeed causative for the disease. Here we identified and characterized a new deleterious ClC-7 mutation in Belgian Blue cattle with a severe symptomatology including perinatal lethality and in most cases gingival hamartomas. By autozygosity mapping and genome-wide sequencing we found a handful of candidate variants, including a cluster of three private SNPs causing the substitution of a conserved tyrosine in the CBS2 domain of ClC-7 by glutamine. The case for ClC-7 was strengthened by subsequent examination of affected calves that revealed severe osteopetrosis. The Y750Q mutation largely preserved the lysosomal localization and assembly of ClC-7/Ostm1, but drastically accelerated its activation by membrane depolarization. These data provide first evidence that accelerated ClC-7/Ostm1 gating per se is deleterious, highlighting a physiological importance of the slow voltage-activation of ClC-7/Ostm1 in lysosomal function and bone resorption. PMID:24159188

  19. Malignant melanoma maxilla

    PubMed Central

    Devi, Seema; Sinha, Richi; Singh, Rakesh Kumar

    2015-01-01

    A malignant melanoma is a highly lethal melanocytic neoplasm. A neoplasm usually affects the skin. Malignant melanomas in the head and neck region are rare, accounting for less than 1% of all melanomas. Malignant melanoma of the nose and paranasal sinuses is an aggressive disease typically presenting at an advanced stage, with a 5-year survival rate ranging 20-30%. Melanomas are tumors arising from melanocytes, which are neuroectodermally derived cells located in the basal layers of the skin. This is a case report of a 35-year-old male, who presented with very aggressive disease and developed liver metastasis.

  20. Brain Malignancies Steering Committee

    Cancer.gov

    The Brain Malignancy Steering Committee evaluates and prioritizes concepts for phase 3 and large phase 2 therapeutic clinical trials to be conducted in the NCI National Clinical Trials Network (NCTN).

  1. Chemoembolization of hepatic malignancy.

    PubMed

    Gonsalves, Carin F; Brown, Daniel B

    2009-01-01

    Treatment of primary and secondary hepatic malignancies with transarterial chemoembolization represents an essential component of interventional oncology. This article discusses patient selection, procedure technique, results, and complications associated with transarterial chemoembolization. PMID:18668189

  2. Thoracic Malignancy Steering Committee

    Cancer.gov

    The Thoracic Malignancy Steering Committee evaluates and prioritizes concepts for phase 3 and large phase 2 therapeutic clinical trials to be conducted in the NCI National Clinical Trials Network (NCTN).

  3. Gastrointestinal Malignancies Faculty

    Cancer.gov

    Mission Statement The Gastrointestinal Malignancies Faculty (GMF) facilitates interactions among basic, epidemiological, translational, and clinical researchers promoting a community of investigators working together for the prevention, diagnosis, and cur

  4. Gastrointestinal Malignancies Faculty

    Cancer.gov

    1) Promote collaborative interactions among NCI basic, epidemiological, translational, and clinical investigators who conduct research in gastrointestinal malignancies; and 2) Facilitate the development of new prevention, diagnosis, and treatment options

  5. Current trends in the treatment of infantile spasms

    PubMed Central

    Tsao, Chang-Yong

    2009-01-01

    Infantile spasms are an epilepsy syndrome with distinctive features, including age onset during infancy, characteristic epileptic spasms, and specific electroencephalographic patterns (interictal hypsarrhythmia and ictal voltage suppression). Adrenocorticotropic hormone (ACTH) was first employed to treat infantile spasms in 1958, and since then it has been tried in prospective and retrospective studies for infantile spasms. Oral corticosteroids were also used in a few studies for infantile spasms. Variable success in cessation of infantile spasms and normalization of electroencephalograms was demonstrated. However, frequent significant adverse effects are associated with ACTH and oral corticosteroids. Vigabatrin has been used since the 1990s, and shown to be successful in resolution of infantile spasms, especially for infantile spasms associated with tuberous sclerosis. It is associated with visual field constriction, which is often asymptomatic and requires perimetric visual field study to identify. When ACTH, oral corticosteroids, and vigabatrin fail to induce cessation of infantile spasms, other alternative treatments include valproic acid, nitrazepam, pyridoxine, topiramate, zonisamide, lamotrigine, levetiracetam, felbamate, ganaxolone, liposteroid, thyrotropin-releasing hormone, intravenous immunoglobulin and a ketogenic diet. Rarely, infantile spasms in association with biotinidase deficiency, phenylketonuria, and pyridoxine-dependent seizures are successfully treated with biotin, a low phenylalanine diet, and pyridoxine, respectively. For medically intractable infantile spasms, some properly selected patients may have complete cessation of infantile spasms with appropriate surgical treatments. PMID:19557123

  6. Control of bone resorption by hematopoietic tissue. The induction and reversal of congenital osteopetrosis in mice through use of bone marrow and splenic transplants

    PubMed Central

    1975-01-01

    The reciprocal transplantation of hematopoietic tissues was carried out on young, lethally irradiated mice of inbred, microphthalmic stock. The cell infusions prepared from the bone marrow or spleen of a normal littermate fully restored capacity to resorb bone and cartilage in the osteopetrotic recipients. Conversely, cell infusions prepared from the spleen of microphthalmic mice induced osteopetrosis in their irradiated, normal littermates. It is concluded that resorption of skeletal matrix is controlled by migratory cells, possibly osteoclastic progenitors, derived from the myelogenous tissues. No evidence was obtained to suggest that skeletal changes observed in the experimental animals were mediated by a graft-vs.-host reaction. The earliest skeletal changes in the experimental mice were detected 2 wk after onset which may represent the length or time required to replace the osteoclast population of the mouse. PMID:1100763

  7. A RANKL G278R mutation causing osteopetrosis identifies a functional amino acid essential for trimer assembly in RANKL and TNF.

    PubMed

    Douni, Eleni; Rinotas, Vagelis; Makrinou, Eleni; Zwerina, Jochen; Penninger, Josef M; Eliopoulos, Elias; Schett, Georg; Kollias, George

    2012-02-15

    Receptor activator of nuclear factor-?B ligand (RANKL), a trimeric tumor necrosis factor (TNF) superfamily member, is the central mediator of osteoclast formation and bone resorption. Functional mutations in RANKL lead to human autosomal recessive osteopetrosis (ARO), whereas RANKL overexpression has been implicated in the pathogenesis of bone degenerative diseases such as osteoporosis. Following a forward genetics approach using N-ethyl-N-nitrosourea (ENU)-mediated random mutagenesis, we generated a novel mouse model of ARO caused by a new loss-of-function allele of Rankl with a glycine-to-arginine mutation at codon 278 (G278R) at the extracellular inner hydrophobic F ?-strand of RANKL. Mutant mice develop severe osteopetrosis similar to Rankl-deficient mice, whereas exogenous administration of recombinant RANKL restores osteoclast formation in vivo. We show that RANKL(G278R) monomers fail to assemble into homotrimers, are unable to bind and activate the RANK receptor and interact with wild-type RANKL exerting a dominant-negative effect on its trimerization and function in vitro. Since G278 is highly conserved within the TNF superfamily, we identified that a similar substitution in TNF, G122R, also abrogated trimerization, binding to TNF receptor and consequently impaired TNF biological activity. Notably, SPD304, a potent small-molecule inhibitor of TNF trimerization that interacts with G122, also inhibited RANKL activity, suggesting analogous inhibitory mechanisms. Our results provide a new disease model for ARO and identify a functional amino acid in the TNF-like core domain essential for trimer formation both in RANKL and in TNF that could be considered a novel potential target for inhibiting their biological activities. PMID:22068587

  8. Hirschsprung's disease with infantile nephropathic cystinosis.

    PubMed

    Mittal, Deepak; Bagga, Arvind; Tandon, Radhika; Sharma, Mehar Chand; Bhatnagar, Veereshwar

    2015-01-01

    The case of a 3-year-old boy diagnosed to have Hirschsprung's disease with infantile nephropathic cystinosis is being reported. Both these conditions are etiologically and genetically different as per current understanding and available information. The association is incidental and has not reported before in the English literature. PMID:26166990

  9. Idiopathic infantile chronic rhegmatogenous retinal detachment.

    PubMed

    Aziz, Hassan A; Berrocal, Audina M; Sisk, Robert A; Murray, Timothy G

    2011-01-01

    The authors describe a 3-month-old female infant with infantile rhegmatogenous retinal detachment with no associated congenital or developmental abnormalities. The unique presentation of this patient indicates that the detachment was a result of an early developmental defect. PMID:21751768

  10. Infantile Amnesia: Forgotten but Not Gone

    ERIC Educational Resources Information Center

    Li, Stella; Callaghan, Bridget L.; Richardson, Rick

    2014-01-01

    Unlike adult memories that can be remembered for many years, memories that are formed early in life are more fragile and susceptible to being forgotten (a phenomenon known as "infantile" or "childhood" amnesia). Nonetheless, decades of research in both humans and nonhuman animals demonstrate the importance of early life…

  11. Pediatric Head and Neck Malignancies.

    PubMed

    Qaisi, Mohammed; Eid, Issam

    2016-02-01

    Head and neck malignancies are rare in pediatric patients, and represent 12% of all pediatric malignancies. The incidence for these head and neck tumors is 1.49 cases per 1,000,000 person-years. Among the most common pediatric head and neck malignancies are lymphomas (27%), neural tumors including primitive neurectodermal tumors (23%), thyroid malignancies (21%), soft tissue sarcomas including rhabdomyosarcoma (12%), nasopharyngeal carcinoma, skeletal and odontogenic malignancies including osteosarcoma, Ewing sarcoma, and ameloblastic carcinoma. This article presents an overview of pediatric head and neck malignancies with emphasis on diagnosis and management. PMID:26614697

  12. Congenital Disseminated Extrarenal Malignant Rhabdoid Tumor.

    PubMed

    Boudjemaa, Sabah; Petit, Arnaud; Dainese, Linda; Bourdeaut, Franck; Lipsett, Jill; Coulomb, Aurore

    2015-01-01

    Soft tissue tumors arising in association with genetic or malformation syndromes have been increasingly reported. Malignant rhabdoid tumor (MRT) is a highly aggressive neoplasm of infancy and young childhood, characterized by typical morphology and biallelic inactivation of the SMARCB1 (INI1/hSNF5/BAF47) gene on chromosome 22q.2 which encodes a subunit of the SWI/SNF ATP-dependent chromatin remodeling complex. Congenital infantile disseminated MRT represents a unique clinicopathologic presentation of this tumor. We report a case occurring in a female neonate who presented at birth a voluminous left thigh mass. Surgical biopsy performed at day 9 showed morphology and immunoprofile of MRT. Staging evaluation identified hypercalcemia and distant nodules. The mass showed rapid growth. Despite chemotherapy, the tumor progressed with exteriorization through the biopsy scar. Chemotherapy was discontinued and treatment limited to palliative care and the child died on day 51. The tumor was homozygous for the SMARCB1 deletion with apparent de novo heterozygous germ line deletion in the infant, not identified in the parents. PMID:25751458

  13. Genetics Home Reference: Osteopetrosis

    MedlinePLUS

    ... bones pinch nerves in the head and face (cranial nerves), often resulting in vision loss, hearing loss, and ... bone marrow ; bone remodeling ; calcium ; cell ; chromosome ; congenital ; cranial nerves ; disability ; dysplasia ; epilepsy ; gene ; hepatosplenomegaly ; immune system ; immunodeficiency ; ...

  14. Malignant tumors of childhood

    SciTech Connect

    Brooks, B.J.

    1986-01-01

    This book contains 34 papers about malignant tumors. some of the titles are: Invasive Cogenital Mesoblastic Nephroma, Leukemia Update, Unusual Perinatal Neoplasms, Lymphoma Update, Gonadal Germ Cell Tumors in Children, Nutritional Status and Cancer of Childhood, and Chemotherapy of Brain tumors in Children.

  15. Malignant Catarrhal Fever

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Malignant catarrhal fever (MCF) is a frequently fatal viral disease of ruminant species, particularly cattle, bison, and deer. Clinical signs vary between species. Two major epidemiologic types of MCF exist, and are defined by the ruminant species that serve as natural reservoir hosts for infection...

  16. Postirradiation malignant fibrous histiocytoma

    SciTech Connect

    Tewfik, H.H.; Tewfik, F.A.; Latourette, H.B.

    1981-02-01

    Three patients who were treated successfully with postoperative external radiation therapy for ovarian carcinoma, endometrial adenocarcinoma, and bilateral retinoblastoma respectively developed years later malignant fibrous histiocytoma (MFH) within the irradiated field. MFH is a recently described soft tissue sarcoma known for its dual fibroblastic and histiocytic differentiation resulting in a pleomorphic histologic appearance.

  17. Malignant Melanoma of the Foot

    MedlinePLUS

    ... Text Size Print Bookmark Malignant Melanoma of the Foot What is Malignant Melanoma? Melanoma is a cancer ... age groups, even the young. Melanoma in the Foot Melanoma that occurs in the foot or ankle ...

  18. Treatment Option Overview (Malignant Mesothelioma)

    MedlinePLUS

    ... Malignant mesothelioma is a disease in which malignant (cancer) cells form in the lining of the chest or ... diagnosed, tests are done to find out if cancer cells have spread to other parts of the body. ...

  19. General Information about Malignant Mesothelioma

    MedlinePLUS

    ... Malignant mesothelioma is a disease in which malignant (cancer) cells form in the lining of the chest or ... diagnosed, tests are done to find out if cancer cells have spread to other parts of the body. ...

  20. Association between infantile spasms and nonaccidental head injury.

    PubMed

    Birca, Ala; D'Anjou, Guy; Carmant, Lionel

    2014-05-01

    Infantile spasms constitute a severe epileptic encephalopathy of infancy with poor long-term developmental outcome. Many diverse etiologies have been associated with infantile spasms, but the pathophysiological process is still not fully understood. We describe 2 cases of previously healthy 1- and 3-month-old infants who suffered a nonaccidental head injury with extensive cerebral lesions. Both presented with acute focal seizures rapidly controlled with phenobarbital. Nevertheless, they developed infantile spasms after a latency period of 3-4 months. Spasms were rapidly controlled with vigabatrin. Both children manifested with developmental delay, either exacerbated (case 1) or elicited (case 2) by infantile spasms. Our report highlights nonaccidental head injury as a risk factor for developing infantile spasms following a seizure-free latency period. A better understanding of the pathophysiology linking accidental brain trauma with infantile spasms could lead to more effective neuroprotective strategies. In the meantime, increased awareness and follow-up are warranted. PMID:23580697

  1. Cytoplasmic expression of Wilms tumor transcription factor-1 (WT1): a useful immunomarker for young-type fibromatoses and infantile fibrosarcoma.

    PubMed

    Magro, Gaetano; Salvatorelli, Lucia; Vecchio, Giada Maria; Musumeci, Giuseppe; Rita, Alaggio; Parenti, Rosalba

    2014-09-01

    There is increasing evidence that Wilms' tumor transcription factor-1 (WT1) is expressed in the cytoplasm of neoplastic cells from different benign and malignant tumors. Only a few studies on WT1 cytoplasmic immunolocalization are available in pediatric tumors. The aim of the present study was to investigate immunohistochemically the expression and distribution of WT1 in a large series of soft tissue fibroblastic/myofibroblastic lesions occurring in children and adolescents. Notably WT1 was not expressed in nodular fasciitis and desmoid-type (adult) fibromatosis, while it stained diffusely and strongly in several infantile-type fibromatoses, such as fibrous hamartoma of infancy, myofibroma/myofibromatosis, and lipofibromatosis. Interestingly, WT1 cytoplasmic expression was also found in all cases (10/10) of infantile fibrosarcomas examined. The present study shows that a diffuse WT1 cytoplasmic expression is of complementary diagnostic value to conventional myofibroblastic markers (?-smooth muscle actin; desmin) in confirming diagnosis of young-type fibromatoses or infantile fibrosarcoma and in ruling out both desmoid-type fibromatoses and nodular fasciitis. WT1 cytoplasmic expression in infantile fibrosarcoma is a novel finding which could be exploitable as an immunomarker for this tumor. Although highly sensitive, WT1 cytoplasmic immunostaining is not specific for infantile fibrosarcoma, and thus it should be evaluated in the context of a wide immunohistochemical panel when pathologists are dealing with spindle cell lesions of soft tissues in children and adolescents. Accordingly we recommend that a correct diagnosis of fibroblastic/myofibroblastic soft tissue lesion in pediatric patients is usually achieved on the basis of a careful correlation of morphological and immunohistochemical findings in the appropriate clinical context. The different cellular localization of WT1, namely nuclear, cytoplasmic or nucleo-cytoplasmic, in different benign and malignant tumors supports the hypothesis that this transcription factor plays a complex role in tumorigenesis, likely as a chameleon protein functioning as either a tumor suppressor gene or an oncogene, depending on cellular context. PMID:25005570

  2. Idiopathic infantile hypercalcaemia--a continuing enigma.

    PubMed Central

    Martin, N D; Snodgrass, G J; Cohen, R D

    1984-01-01

    Seventy six children with documented Fanconi-type idiopathic infantile hypercalcaemia were studied and compared with 41 with the Williams-Beuren syndrome. Clinical comparison showed, as expected, very close similarities but also considerable differences, particularly in the severity of feeding problems and the degree of failure to thrive. The estimated incidence of idiopathic infantile hypercalcaemia alone has remained constant for the past 20 years, at approximately 18 cases per year in the United Kingdom (1 per 47 000 total live births). Long term morbidity in these children is mainly due to mental handicap and arteriopathy, but hypertension (29%), kyphoscoliosis (19%), hyperacusis (75%), and obesity (50%) may be added complications. In one child, hypercalcaemia recurred during adolescence but this seems to be excessively rare. More detailed investigation before treatment is required to discover the aetiology of hypercalcaemia in this condition. Images Fig. 2 PMID:6465928

  3. Infantile systemic hyalinosis in identical twins

    PubMed Central

    Koonuru, Mahesh Kumar; Venugopal, Satya Prasad

    2015-01-01

    Summary Infantile systemic hyalinosis (ISH) is a rare disorder belonging to the heterogeneous group of genetic fibromatoses. It is a rare, progressive, fatal autosomal recessive condition characterized by widespread deposition of hyaline material in many tissues caused by mutations in the anthrax toxin receptor 2 gene - ANTXR2. It presents hyperpigmented skin over bony prominences. Characteristic purplish patches develop over the medial and lateral malleoli of the ankles, the metacarpophalangeal joints, spine and elbows, with progressive joint contractures, osteopenia, skin abnormalities and chronic severe pain. The present case reports the occurrence of infantile systemic hyalinosis in twin brothers five months of age who had come for early intervention for joint contractures representing characteristic brownish patches over bony prominences. ISH cases reported until this date have been less than 20 and the present case is unique in nature since this is the first time ISH is reported in twins globally and the symptoms have been identified at an early age. PMID:26668783

  4. Infantile systemic hyalinosis in identical twins.

    PubMed

    Koonuru, Mahesh Kumar; Venugopal, Satya Prasad

    2015-11-01

    Infantile systemic hyalinosis (ISH) is a rare disorder belonging to the heterogeneous group of genetic fibromatoses. It is a rare, progressive, fatal autosomal recessive condition characterized by widespread deposition of hyaline material in many tissues caused by mutations in the anthrax toxin receptor 2 gene - ANTXR2. It presents hyperpigmented skin over bony prominences. Characteristic purplish patches develop over the medial and lateral malleoli of the ankles, the metacarpophalangeal joints, spine and elbows, with progressive joint contractures, osteopenia, skin abnormalities and chronic severe pain. The present case reports the occurrence of infantile systemic hyalinosis in twin brothers five months of age who had come for early intervention for joint contractures representing characteristic brownish patches over bony prominences. ISH cases reported until this date have been less than 20 and the present case is unique in nature since this is the first time ISH is reported in twins globally and the symptoms have been identified at an early age. PMID:26668783

  5. Infantile Spasms: Little Seizures, BIG Consequences

    PubMed Central

    Shields, W Donald

    2006-01-01

    Infantile spasms is one of the “catastrophic childhood epilepsies” because of the difficulty in controlling seizures and the association with mental retardation. However, early recognition, a careful diagnostic evaluation, and proper treatment may allow some children to attain seizure control and to achieve a normal, or at least much improved, level of development. Thus, there is the opportunity to have an important impact in the lives of these unfortunate children and their families. PMID:16761063

  6. Coincidence of Tourette's disorder and infantile autism.

    PubMed

    Realmuto, G M; Main, B

    1982-12-01

    This is a single-case report of the syndrome of Tourette's disorder (GTS) and infantile autism (IA) occurring together. Neuroleptics were not administered prior to the onset of GTS. The heuristic value of comparing the different biochemical mechanisms of the syndromes and its implication for diagnosis and etiology is discussed. Norepinephrine is thought to be at least one transmitter that differentiates the syndromes. PMID:6131060

  7. Lymphoscintigraphy in malignant melanoma

    SciTech Connect

    Berman, C.G.; Norman, J.; Cruse, C.W.; Reintgen, D.S.; Clark, R.A. )

    1992-01-01

    The development and rationale for the use of lymphoscintigraphy in the preoperative evaluation of patients with malignant melanoma being considered for elective lymph node dissection is reviewed. This overview is updated by an analysis of 135 patients with early stage malignant melanoma involving the head, neck, shoulders, and trunk at Moffitt Cancer Center and Research Institute at the University of South Florida (Tampa, FL). High discordancy rates (overall, 41%) were seen between drainage patterns predicted from historical anatomical guidelines and those revealed by the lymphoscintigraphic examination. The high discordancy rate was most pronounced in the head (64%) and the neck (73%). Surgical management was changed in 33% of the patients, overall. A preoperative lymphoscintigram is recommended for all patients with melanoma with head, neck, and truncal lesions evaluated for elective lymph node dissection as the lymphatic drainage patterns are often unpredictable and variable.

  8. Nicotinamide Phosphoribosyltransferase in Malignancy

    PubMed Central

    Shackelford, Rodney E.; Mayhall, Kim; Maxwell, Nicole M.; Kandil, Emad

    2013-01-01

    Nicotinamide phosphoribosyltransferase (Nampt) catalyzes the rate-limiting step of nicotinamide adenine dinucleotide (NAD) synthesis. Both intracellular and extracellular Nampt (iNampt and eNampt) levels are increased in several human malignancies and some studies demonstrate increased iNampt in more aggressive/invasive tumors and in tumor metastases. Several different molecular targets have been identified that promote carcinogenesis following iNampt overexpression, including SirT1, CtBP, and PARP-1. Additionally, eNampt is elevated in several human cancers and is often associated with a higher tumor stage and worse prognoses. Here we review the roles of Nampt in malignancy, some of the known mechanisms by which it promotes carcinogenesis, and discuss the possibility of employing Nampt inhibitors in cancer treatment. PMID:24386506

  9. Hyaluronan in human malignancies

    SciTech Connect

    Sironen, R.K.; Department of Pathology, Kuopio University Hospital, P.O. Box 1777, FI-70211 Kuopio ; Tammi, M.; Tammi, R.; Auvinen, P.K.; Anttila, M.; Department of Gynecology and Obstetrics, Kuopio University Hospital, P.O. Box 1777, FI-70211 Kuopio ; Kosma, V-M.

    2011-02-15

    Hyaluronan, a major macropolysaccharide in the extracellular matrix of connective tissues, is intimately involved in the biology of cancer. Hyaluronan accumulates into the stroma of various human tumors and modulates intracellular signaling pathways, cell proliferation, motility and invasive properties of malignant cells. Experimental and clinicopathological evidence highlights the importance of hyaluronan in tumor growth and metastasis. A high stromal hyaluronan content is associated with poorly differentiated tumors and aggressive clinical behavior in human adenocarcinomas. Instead, the squamous cell carcinomas and malignant melanomas tend to have a reduced hyaluronan content. In addition to the stroma-cancer cell interaction, hyaluronan can influence stromal cell recruitment, tumor angiogenesis and epithelial-mesenchymal transition. Hyaluronan receptors, hyaluronan synthases and hyaluronan degrading enzymes, hyaluronidases, are involved in the modulation of cancer progression, depending on the tumor type. Furthermore, intracellular signaling and angiogenesis are affected by the degradation products of hyaluronan. Hyaluronan has also therapeutic implications since it is involved in multidrug resistance.

  10. Endobronchial tuberculosis mimicking malignancy

    PubMed Central

    Patel, Shahid M; Iyer, Aparna; Jayalakshmi, TK; Nair, Girija

    2015-01-01

    Endobronchial tuberculosis has a very varied presentation. Diagnosis is often very challenging as typical radiological features are absent and sputum smear for acid-fast bacilli is often negative. However, detection is essential as it may lead to long-term sequelae such as bronchial stenosis. Bronchoscopy is a very useful investigation in such cases. Our case is a rare manifestation of endobronchial tuberculosis as it mimicked malignancy.

  11. Part Two: Infantile Spasms--The New Consensus

    ERIC Educational Resources Information Center

    Pellock, John M.; O'Hara, Kathryn

    2011-01-01

    This article presents the conclusion made by the consensus group regarding infantile spasms. The consensus group concluded that "infantile spasms are a major form of severe epileptic encephalopathy of early childhood that results in neurodevelopmental regression and imposes a significant health burden." The entire group agrees that the best…

  12. Politicas del Bienestar del Programa de Dasarrollo Infantil Callier

    E-print Network

    O'Toole, Alice J.

    familias, el Programa de Desarrollo Infantil Callier busca promover la salud de los niños a través de Departamento de la Familia y de Protección de las Normas Mínimas para el cuidado infantil Saludable y Activo nutricional se proporciona a las familias a través de carteles, pizarras de anuncios, y en los eventos

  13. CSF B-Endorphin Levels in Patients with Infantile Autism.

    ERIC Educational Resources Information Center

    Nagamitsu, Shinichiro; And Others

    1997-01-01

    A Japanese study measured CSF (cerebrospinal fluid) levels of beta-endorphin in 19 children (ages 4-6) with infantile autism and in 3 children (ages 10-14) with Rett syndrome. In infantile autism, levels did not differ significantly from control participants (n=23). However, levels were significantly higher in those with Rett syndrome. (Author/CR)

  14. Physiological Regulation and Infantile Anorexia: A Pilot Study

    ERIC Educational Resources Information Center

    Chatoor, Irene; Ganiban, Jody; Surles, Jaclyn; Doussard-Roosevelt, Jane

    2004-01-01

    Objective: To examine whether infantile anorexia is associated with physiological dysregulation. Method: This study included eight toddlers with infantile anorexia and eight healthy eaters matched for age, race, socioeconomic status, and gender. Physiological measures of heart period and respiratory sinus arrhythmia were assessed across three…

  15. Salivary Gland Malignancies.

    PubMed

    Rodriguez, Cristina P; Parvathaneni, Upendra; Méndez, Eduardo; Martins, Renato G

    2015-12-01

    Salivary gland malignant tumors represent a diverse group of neoplasms. Their low incidence makes research studies challenging, with most therapeutic recommendations based on case reviews, single-arm trials, or small randomized trials. The standard of care for localized disease is surgical resection. Radiotherapy is the preferred local therapy when surgery is not possible or if there is significant morbidity. When symptomatic metastatic disease develops, systemic therapy is considered. Recent trial accrual success with a cooperative group, treatments based on defined molecular targets, and the development of immunotherapies all hold promise in improving the care of patients with these tumors. PMID:26568553

  16. Radioimmunotherapy of malignancies

    SciTech Connect

    Reilly, R.M. )

    1991-05-01

    The critical issues in radioimmunotherapy are highlighted, and novel ways of improving the therapeutic indexes of radioimmunotherapeutic agents are outlined. The use of radioactively labeled monoclonal antibodies to treat malignant tumors has been investigated in animals and humans. Radionuclides suitable for labeling antibodies for such use include iodine 125, iodine 131, yttrium 90, rhenium 188, and copper 67. Radiobiological factors to be considered in radioimmunotherapy include the size and density of the tumor and the ability of a radiolabeled antibody to penetrate the tumor nodule. The dose of radiation required to destroy a tumor varies; however, the whole-body dose must not exceed 200 rads to avoid irreversible toxicity to the bone marrow. Despite the theoretical inadequacy of radiation doses to tumors indicated by conventional dosimetry, responses have been observed in animals and humans. More reliable and accurate dosimetric methods are under development. The induction of human antimouse antibodies can alter the pharmacokinetics of radiolabeled antibodies. Improving the therapeutic index of radioimmunotherapeutic agents may be achieved through regional therapy, administering a secondary antibody to improve clearance, combining radioimmunotherapy with external-beam irradiation, using an avidin-biotin conjugate system to deliver the radiolabeled antibodies, and addressing the problem of tumor antigen heterogeneity. Researchers are working to reduce or eliminate the clinical problems associated with radioimmunotherapy. Hematologic malignancies, such as lymphomas, are more likely than solid tumors to respond satisfactorily. 110 refs.

  17. Probiotics for infantile colic: a systematic review

    PubMed Central

    2013-01-01

    Background Infantile colic is a common paediatric condition which causes significant parental distress. Increased intestinal coliform colonization in addition to alteration in Lactobacillus abundance and distribution may play an important role in its pathogenesis. The objectives of this systematic review are to evaluate the efficacy of probiotic supplementation in the reduction of crying time and successful treatment of infantile colic. Methods Literature searches were conducted of MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials. Only randomized controlled trials enrolling term, healthy infants with colic were included. A meta-analysis of included trials was performed utilizing the Cochrane Collaboration methodology. Results Three trials that enrolled 220 breastfed infants met inclusion criteria, of which 209 infants were available for analysis. Two of the studies were assessed as good quality. Lactobacillus reuteri (strains-American Type Culture Collection Strain 55730 and DSM 17 938) was the only species utilized in the therapeutic intervention. Two of the trials were industry funded. Probiotic supplementation compared to simethicone or placebo significantly and progressively shortened crying times to 7 days reaching a plateau at three weeks post initiation of therapy [mean difference ?56.03 minutes; 95% CI (?59.92, -52.15)]. Similarly, probiotics compared to placebo significantly increased the treatment success of infantile colic with a relative risk (RR) of 0.06; 95% CI (0.01, 0.25) and a number needed to treat of 2. Conclusions Although L. reuteri may be effective as a treatment strategy for crying in exclusively breastfed infants with colic, the evidence supporting probiotic use for the treatment of infant colic or crying in formula-fed infants remains unresolved. Results from larger rigorously designed studies will help draw more definitive conclusions. PMID:24238101

  18. Looking for new treatments of Infantile Colic

    PubMed Central

    2014-01-01

    Infantile colic is a common disturbance occurring in the first three months of life. It is a benign condition and one of the main causes of pediatric consultation in the early part of life because of its great impact on family life. Some pediatricians are prone to undervalue this issue mainly because of the lack of evidence based medicine guidelines. Up to now, there is no consensus concerning management and treatment. Literature reports growing evidence about the effectiveness of dietary, pharmacological, complementary and behavioral therapies as options for the management of infantile colic. Dietary approach, usually based on the avoidance of cow’s milk proteins in breast-feeding mothers and bottle-fed infants, more recently has seen the rise of new special formulas, such as partially hydrolyzed proteins and low lactose added with prebiotics or probiotics: their efficacy needs to be further documented. Investigated pharmacological agents are Simethicone and Cimetropium Bromide: the first is able to reduce bloating while the second could reduce fussing crying, but it has been tested only for severe infantile colic. No other pain relieving agents have been proposed until now, but some clinical trials are ongoing for new drugs. There is limited evidence supporting the use of complementary and alternative treatments (herbal supplements, manipulative approach and acupuncture) or behavioral interventions. Recent studies have focused the role of microbiota in the pathogenesis of this disturb and so new treatments, such as probiotics, have been proposed, but only few strains have been tested. Further investigations are needed in order to provide evidence-based guidelines. PMID:24898541

  19. Infantile spasms syndrome in monozygotic twins.

    PubMed Central

    Pavone, L; Mollica, F; Incorpora, G; Pampiglione, G

    1980-01-01

    The infantile spasms syndrome appeared on the same day in a pair of monozygotic twins at age 6 months. Clinical, electroencephalographic, and neuroradiological findings during the development of the disease are reported. One of the twins was treated with ACTH and in his case clinical and electroencephalographic improvement was more rapid than in the other who was treated with clonazepam. While the computer tomography scan initially showed in each twin an area of low density in the right fronto-parietal region, this had disappeared in the tomograms obtained about 8 months later. PMID:6254446

  20. Infantile haemangioma and ?-blockers in otolaryngology.

    PubMed

    Leboulanger, N; Cox, A; Garabedian, E-N; Denoyelle, F

    2011-11-01

    Infantile haemangioma (IH) is the most common tumour during early childhood. Although these benign lesions resolve spontaneously, up until recently laryngotracheal sites of IH required invasive management. The dramatic efficacy of ?-blockers on IH has radically changed the prognosis. Surgery is now no longer indicated as first-line therapy, but should only be performed for difficult, refractory cases, or in the presence of absolute contraindications to ?-blockers. Long-term steroid therapy is also no longer indicated. Propranolol can be used as first-line, single-agent therapy. PMID:21498145

  1. Acupuncture in the treatment of infantile colic.

    PubMed

    Landgren, Kajsa; Raith, Wolfgang; Schmölzer, Georg M; Skjeie, Holgeir; Skonnord, Trygve

    2015-01-01

    Regarding the recently published review "Looking for new treatments of Infantile Colic" by Savino et al. we want to add that positive effects of acupuncture have been demonstrated to release pain and agitation and that acupuncture seems to be a safe treatment when performed by trained acupuncturists. Inconclusive results in the few published articles on the subject can be due to different acupuncture points, different insertion time, different needling methods, differences in the outcome variables, in how the crying was measured and insufficient sample sizes. Further research is needed on understanding the utility, safety, and effectiveness of acupuncture in infants with colic. PMID:25588517

  2. Family pathology and the infantile neurosis.

    PubMed

    Calogeras, R C; Alston, T M

    1985-01-01

    In this study we have attempted to investigate the connection (in the sense of a complex interplay) between the infantile and the adult neurosis where severe family pathology has been an important determining force. In the clinical illustrations of two female patients we tried to determine the fate (i.e. in terms of the compulsion to repeat) of the early infantile conflicts and experiences within the purview of their pathological family condition. In sorting this out, we distinguished between those repetitions viewed as passive reproductions and those repetitions viewed, as re-creative; the former finding their way essentially into the adult neurosis, the latter finding their way into parts of the personality under the aegis of their ego's organizing activity. The fashion in which the family pathology impinged upon the adult neurosis made the development of the transference in the analytic situation a most difficult arena for clarification, since there was a tendency to confuse past (early) events, past fantasy, current reality and current fantasy. In concluding we noted that both Oedipus complex and oedipal drama came together in these patients, revealing the link between the tragedy of their life-long family situation and what was termed a 'fate neurosis'. PMID:4044124

  3. [Hematologic abnormalities in infantile visceral leishmaniasis].

    PubMed

    Chouchene, S; Braham, N; Bouatay, A; Hizem, S; Berriri, S; Eljemai, A; Boughamoura, L; Kortas, M

    2015-11-01

    The clinical and biological manifestations of visceral leishmaniasis are often confusing, most particularly because it can mimic and lead to a variety of hematological disorders. The aim of this study was to investigate the hematologic abnormalities observed in infantile visceral leishmaniasis from January 2000 and December 2013. The study included 35 children with a mean age of 3.5 years. Clinical manifestations were dominated by splenomegaly, fever, and paleness, defining the classic triad in 16% of our patients. Anemia was present in all patients. Leukopenia was found in 51% of the cases. Thrombocytopenia was observed in 48% of our patients and 36% had pancytopenia. All cases were confirmed by the presence of Leishman bodies (amastigotes) in the bone marrow smears. Quantitative and qualitative megakaryocyte abnormalities were found. Similarly, dysgranulopoiesis was observed in 31% of the cases, eosinophilia was present in 6%, erythroid hypoplasia in 3%, and erythroid hyperplasia in 34%. Different features of dyserythropoiesis were revealed in 71% of the patients with images of hemophagocytosis in 6% and multiple dysplasias in 9%. The knowledge of these hematological abnormalities associated with infantile visceral leishmaniasis can assist us in searching for Leishman bodies in the bone marrow smears to provide a diagnosis more quickly without necessarily resorting to more sophisticated tests. PMID:26433577

  4. The malignant primate?

    PubMed

    de Grouchy, J

    1991-01-01

    Speciation and carcinogenesis result from genomic instability at the gametic or at the somatic levels. After an infinity of trials they occur, by chromosome rearrangements, in single individuals or in single cells and evolve by similar chromosomal or clonal evolutions. Loss of heterozygosity for the first event is essential in both processes: in evolution, a chromosomal rearrangement, a pericentric inversion or a Robertsonian fusion, must become homozygous to ensure a reproductive barrier for a new species; Knudson's two-event sequence is a similar situation in cancer. Position effect is equally important: we have shown overexpression of the SOD1 gene in the orangutan phylum probably by an intrachromosomal rearrangement; the t(9;22) in CML acts by typical position effect. Parental imprinting underlies the evolution of genome function and the unset of certain cancers. Evolution and malignancy are interweaved by viruses and oncogenes since the dawn of life. Cancer uses its intelligence to expand and to destroy the other tissues, using subtle metabolic pathways and a variety of tricks to metastasize other cells. It always wins but saws the branch on which it sits. Mankind also grows exponentially, killing thousands of other species, poisoning the oceans and soft waters, polluting the atmosphere, all for his egoistic needs. Man also travels and metastasizes other Earths. He modifies his genome or that of other species, and develops new technologies for his reproduction. He can destroy the planet in an eyeblink. To be or not to be the malignant primate, that will be the dilemma for the 21st Century. PMID:1809219

  5. Evidence-based guideline update: Medical treatment of infantile spasms

    PubMed Central

    Go, C.Y.; Mackay, M.T.; Weiss, S.K.; Stephens, D.; Adams-Webber, T.; Ashwal, S.; Snead, O.C.

    2012-01-01

    Objective: To update the 2004 American Academy of Neurology/Child Neurology Society practice parameter on treatment of infantile spasms in children. Methods: MEDLINE and EMBASE were searched from 2002 to 2011 and searches of reference lists of retrieved articles were performed. Sixty-eight articles were selected for detailed review; 26 were included in the analysis. Recommendations were based on a 4-tiered classification scheme combining pre-2002 evidence and more recent evidence. Results: There is insufficient evidence to determine whether other forms of corticosteroids are as effective as adrenocorticotropic hormone (ACTH) for short-term treatment of infantile spasms. However, low-dose ACTH is probably as effective as high-dose ACTH. ACTH is more effective than vigabatrin (VGB) for short-term treatment of children with infantile spasms (excluding those with tuberous sclerosis complex). There is insufficient evidence to show that other agents and combination therapy are effective for short-term treatment of infantile spasms. Short lag time to treatment leads to better long-term developmental outcome. Successful short-term treatment of cryptogenic infantile spasms with ACTH or prednisolone leads to better long-term developmental outcome than treatment with VGB. Recommendations: Low-dose ACTH should be considered for treatment of infantile spasms. ACTH or VGB may be useful for short-term treatment of infantile spasms, with ACTH considered preferentially over VGB. Hormonal therapy (ACTH or prednisolone) may be considered for use in preference to VGB in infants with cryptogenic infantile spasms, to possibly improve developmental outcome. A shorter lag time to treatment of infantile spasms with either hormonal therapy or VGB possibly improves long-term developmental outcomes. PMID:22689735

  6. Cerebrospinal Fluid Corticotropin and Cortisol Are Reduced in Infantile Spasms

    PubMed Central

    Baram, Tallie Z.; Mitchell, Wendy G.; Hanson, Rebecca A.; Snead, O. Carter; Horton, E.J.

    2012-01-01

    Infantile spasms respond to ACTH, and levels of the hormone in cerebrospinal fluid of untreated infants with this disorder were found to be lower than in age-matched controls. In this study we analyzed cerebrospinal fluid Cortisol and ACTH using improved immunoassays in a larger cohort of infants with infantile spasms. Analysis of 20 patients and 15 age-matched controls revealed significantly lower levels of both ACTH and Cortisol in the cerebrospinal fluid. These data, combined with the efficacy of ACTH and glucocorticoids for infantile spasms, support an involvement of the brain-adrenal-axis in this disorder. PMID:8534274

  7. Dysosteosclerosis Presents as an “Osteoclast-Poor” Form of Osteopetrosis: Comprehensive Investigation of a 3-Year-Old Girl and Literature Review

    PubMed Central

    Whyte, Michael P; Wenkert, Deborah; McAlister, William H; Novack, Deborah V; Nenninger, Angie R; Zhang, Xiafang; Huskey, Margaret; Mumm, Steven

    2010-01-01

    Dysosteosclerosis (DSS), an extremely rare dense bone disease, features short stature and fractures and sometimes optic atrophy, cranial nerve palsy, developmental delay, and failure of tooth eruption in infancy or early childhood consistent with osteopetrosis (OPT). Bone histology during childhood shows unresorbed primary spongiosa from deficient osteoclast action. Additionally, there is remarkable progressive flattening of all vertebrae and, by adolescence, paradoxical metaphyseal osteopenia with thin cortical bone. Reports of consanguinity indicate autosomal recessive inheritance, yet more affected males than females suggest X-linked recessive inheritance. We investigated a nonconsanguineous girl with DSS. Osteosclerosis was discovered at age 7 months. Our studies, spanning ages 11 to 44 months, showed weight at approximately 50th percentile, and length diminishing from approximately 30th percentile to –2.3 SD. Head circumference was +4 SD. The patient had frontal bossing, blue sclera, normal teeth, genu valgum, and unremarkable joints. Radiographs showed orbital and facial sclerosis, basilar thickening, bone-in-bone appearance of the pelvis, sclerotic long bone ends, and fractures of ribs and extremities. Progressive metaphyseal widening occurred as vertebrae changed from ovoid to flattened and became beaked anteriorly. A hemogram was normal. Consistent with OPT, serum parathyroid hormone (PTH) concentrations reflected dietary calcium levels. Serum bone alkaline phosphatase, osteocalcin, and TRACP-5b were subnormal. The iliac crest contained excessive primary spongiosa and no osteoclasts. No mutations were identified in the splice sites or exons for the genes encoding chloride channel 7, T-cell immune regulator 1, OPT-associated transmembrane protein 1, and monocyte colony-stimulating factor (M-CSF) and its receptor C-FMS, ANKH, OPG, RANK, and RANKL. Genomic copy-number microarray was unrevealing. Hence, DSS is a distinctive OPT of unknown etiology featuring osteoclast deficiency during early childhood. How osteopenia follows is an enigma of human skeletal pathobiology. © 2010 American Society for Bone and Mineral Research. PMID:20499338

  8. Dipartimento di Pediatria e Neuropsichiatria Infantile Sapienza Universit di Roma

    E-print Network

    Di Pillo, Gianni

    PRESTAZIONE: Elaborazione di dati raccolti presso il Centro Residenziale "Macondo" su un'utenza formata da Infantile ­ SAPIENZA e presso il Centro Residenziale "Macondo" PUBBLICAZIONE: Il presente avviso sarà

  9. Genetics Home Reference: X-linked infantile nystagmus

    MedlinePLUS

    ... infantile nystagmus is a condition characterized by abnormal eye movements. Nystagmus is a term that refers to involuntary ... the first six months of life. The abnormal eye movements may worsen when an affected person is feeling ...

  10. [Not diagnosable malignant melanomas].

    PubMed

    Neuber, H; Lippold, A; Hundeiker, M

    1991-04-01

    Of the 3574 malignant melanomas treated in Hornheide between December 1981 and August 1990 (not including preinvasive cases) 97 were not immediately recognized. These tumours did not look like melanomas. In 72% they were smaller than 10 mm in diameter, and in 20%, smaller than 5 mm. Clark's so often quoted "pencil rule" should no longer be used as an aid to exclusion of invasive melanoma. Localization of the unrecognized melanomas was on the head and neck in 22% of cases. In 37%, the patients were under the age of 40 years. No less than 25% of the patients had multiple melanomas. Many of these melanomas. Many of these melanomas were thin tumours (less than 0.75 mm in 55% and less than 1.5 mm in 77%). This explains why more than 50% of the lesions are described as "macules". The most common incorrect diagnoses were dysplastic naevi (44%) and common (23%) naevi. The most important anamnestic criteria are the patients' own statements about changes in size, colour and shape. These "dynamic" elements must be more carefully observed and documented during process of the clinical diagnosis. PMID:1860796

  11. A MODEL OF SYMPTOMATIC INFANTILE SPASMS SYNDROME

    PubMed Central

    Scantlebury, Morris H.; Galanopoulou, Aristea S.; Chudomelova, Lenka; Raffo, Emmanuel; Betancourth, David; Moshé, Solomon L.

    2009-01-01

    Infantile spasms are characterized by age-specific expression of epileptic spasms, hypsarrhythmia and often result in significant cognitive impairment. Other epilepsies or autism often ensue especially in symptomatic IS (SIS). Cortical or subcortical damage, including white matter, have been implicated in the pathogenesis of SIS. To generate a model of SIS, we recreated this pathology by injecting rats with lipopolysaccharide and doxorubicin intracerebrally at postnatal day (P) 3 and with p-chlorophenylalanine intraperitoneally at P5. Spasms occurred between P4–13 and were associated with ictal EEG correlates, interictal EEG abnormalities and neurodevelopmental decline. After P9 other seizures, deficits in learning and memory, and autistic-like behaviors (indifference to other rats, increased grooming) were observed. Adrenocorticotropic hormone (ACTH) did not affect spasms. Vigabatrin transiently suppressed spasms at P5. This new model of SIS will be useful to study the neurobiology and treatment of SIS, including those that are refractory to ACTH. PMID:19945533

  12. ACTH therapy in infantile spasms: side effects.

    PubMed Central

    Riikonen, R; Donner, M

    1980-01-01

    162 children with infantile spasms were treated with ACTH at the Children's Hospital, Helsinki, and at the Aurora Hospital, Helsinki, during 1960--76. In a large proportion (37%) of the children the treatment caused pronounced side effects, and the mortality was 4.9%. The most common complications were infections: septic infections, pneumonias, and urinary and gastrointestinal infections. Other side effects were arterial hypertension (11), osteoporosis (2), hypokalaemic alkalosis (2), and other marked electrolyte disturbances (10). In children necropsy showed fresh intracerebral haemorrhages. Four children developed oliguria and hyperkalaemia during and after withdrawal of ACTH. One of them had tubular necrosis confirmed by renal biopsy. Infections were significantly more common with large doses (120 units) of ACTH than with small ones (40 units). It is concluded that side effects, even severe ones, are more common during treatment than had been assumed. Careful watch is important before and after treatment. The benefit of very high dosages should also be reconsidered. PMID:6254450

  13. Infantile hypertrophic pyloric stenosis: an infectious cause?

    PubMed

    Sherwood, W; Choudhry, M; Lakhoo, K

    2007-01-01

    The aetiology of infantile hypertrophic pyloric stenosis (IHPS) remains unclear. The aim of this study was to test the hypothesis that a common bacterium, Helicobacter pylori (HP) may be implicated in the pathogenesis of IHPS. Thirty-nine consecutive infants with confirmed IHPS had their stool analysed with an enzyme immunoassay for the presence of HP. An age/sex-matched group of infants with unrelated surgical conditions were also tested. No positive results for the presence of HP stool antigen were obtained in the study nor the control group. The results of this study demonstrate no causative link between HP and IHPS. A genetic basis has been implicated for IHPS. However, evidence does exist that IHPS is a condition acquired after birth and that an infective agent may be involved in the pathogenesis. Further studies are required to elucidate perinatal factors that may induce the expression of this condition in a genetically sensitive individual. PMID:17031712

  14. A genetic and biologic classification of infantile spasms

    PubMed Central

    Paciorkowski, Alex R.; Thio, Liu Lin; Dobyns, William B.

    2011-01-01

    Infantile spasms are an age-dependent epilepsy that are highly associated with cognitive impairment, autism, and movement disorders. Previous classification systems have focused on a distinction between symptomatic and cryptogenic etiologies, and have not kept pace with the recent discoveries of mutations in genes in key pathways of central nervous system development in patients with infantile spasms. Children with certain genetic syndromes are much more likely to have infantile spasms, and we review the literature to propose a genetic classification of these disorders. Children with these genetic associations with infantile spasms also have phenotypes beyond epilepsy that may be explained by recent advances in the understanding of underlying biological mechanisms. We therefore also propose a biologic classification of the genes highly associated with infantile spasms, and articulate models for infantile spasms pathogenesis based on that data. The two best described pathways of pathogenesis are abnormalities in the gene regulatory network of GABAergic forebrain development, and abnormalities in molecules expressed at the synapse. We intend for these genetic and biologic classifications to be flexible, and hope that they will encourage much needed progress in syndrome recognition, clinical genetic testing, and ultimately the development of new therapies that target specific pathways of pathogenesis. PMID:22114996

  15. Malignant external otitis: CT evaluation

    SciTech Connect

    Curtin, H.D.; Wolfe, P.; May, M.

    1982-11-01

    Malignant external otitis is an aggressive infection caused by Pseudomonas aeruginosa that most often occurs in elderly diabetics. Malignant external otitis often spreads inferiorly from the external canal to involve the subtemporal area and progresses medially towards the petrous apex leading to multiple cranial nerve palsies. The computed tomographic (CT) findings in malignant external otitis include obliteration of the normal fat planes in the subtemporal area as well as patchy destruction of the bony cortex of the mastoid. The point of exit of the various cranial nerves can be identified on CT scans, and the extent of the inflammatory mass correlates well with the clinical findings. Four cases of malignant external otitis are presented. In each case CT provided a good demonstration of involvement of the soft tissues at the base of the skull.

  16. AMG 319 Lymphoid Malignancy FIH

    ClinicalTrials.gov

    2015-02-16

    Cancer; Chronic Lymphocytic Leukemia; Diffuse Large Cell Lymphoma; Hematologic Malignancies; Hematology; Leukemia; Low Grade Lymphoma; Lymphoma; Mantle Cell Lymphoma; Non-Hodgkin's Lymphoma; Oncology; Oncology Patients; T Cell Lymphoma; Tumors

  17. Ibrutinib for B cell malignancies

    PubMed Central

    2014-01-01

    Research over the role of Bruton’s agammaglobulinemia tyrosine kinase (BTK) in B-lymphocyte development, differentiation, signaling and survival has led to better understanding of the pathogenesis of B-cell malignancies. Down-regulation of BTK activity is an attractive novel strategy for treating patients with B-cell malignancies. Ibrutinib (PCI-32765), a potent inhibitor of BTK induces impressive responses in B-cell malignancies through irreversible bond with cysteine-481 in the active site of BTK (TH/SH1 domain) and inhibits BTK phosphorylation on Tyr223. This review discussed in details the role of BTK in B-cell signaling, molecular interactions between B cell lymphoma/leukemia cells and their microenvironment. Clinical trials of the novel BTK inhibitor, ibrutinib (PCI-32765), in B cell malignancies were summarized. PMID:24472371

  18. Drugs Approved for Malignant Mesothelioma

    Cancer.gov

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for malignant mesothelioma. The list includes generic names and brand names. The drug names link to NCI's Cancer Drug Information summaries.

  19. [Malignant tumours of the hand].

    PubMed

    Knudsen, Britt Mejer; Rasmussen, Per Joen Svabo; Lausten, Gunnar Schwarz; Jensen, Nina Vendel; Søe, Niels Henrik

    2011-05-30

    Malignant tumours of the hand are rare and are often misdiagnosed. A painful swelling of the hand or digits are often diagnosed with an infection, benign tumours such as ganglion cysts, or arthritis. Wounds that do not heal despite adequate treatment should be biopsied to rule out malignancy. A correct diagnosis without delay is important because the life expectancy, due to a metastasis on the hand or fingers is approximately six months. PMID:21627901

  20. Malignant hyperthermia: a review.

    PubMed

    Rosenberg, Henry; Pollock, Neil; Schiemann, Anja; Bulger, Terasa; Stowell, Kathryn

    2015-01-01

    Malignant hyperthermia (MH) is a pharmacogenetic disorder of skeletal muscle that presents as a hypermetabolic response to potent volatile anesthetic gases such as halothane, sevoflurane, desflurane, isoflurane and the depolarizing muscle relaxant succinylcholine, and rarely, in humans, to stressors such as vigorous exercise and heat. The incidence of MH reactions ranges from 1:10,000 to 1: 250,000 anesthetics. However, the prevalence of the genetic abnormalities may be as great as one in 400 individuals. MH affects humans, certain pig breeds, dogs and horses. The classic signs of MH include hyperthermia, tachycardia, tachypnea, increased carbon dioxide production, increased oxygen consumption, acidosis, hyperkalaemia, muscle rigidity, and rhabdomyolysis, all related to a hypermetabolic response. The syndrome is likely to be fatal if untreated. An increase in end-tidal carbon dioxide despite increased minute ventilation provides an early diagnostic clue. In humans the syndrome is inherited in an autosomal dominant pattern, while in pigs it is autosomal recessive. Uncontrolled rise of myoplasmic calcium, which activates biochemical processes related to muscle activation leads to the pathophysiologic changes. In most cases, the syndrome is caused by a defect in the ryanodine receptor. Over 400 variants have been identified in the RYR1 gene located on chromosome 19q13.1, and at least 34 are causal for MH. Less than 1 % of variants have been found in CACNA1S but not all of these are causal. Diagnostic testing involves the in vitro contracture response of biopsied muscle to halothane, caffeine, and in some centres ryanodine and 4-chloro-m-cresol. Elucidation of the genetic changes has led to the introduction of DNA testing for susceptibility to MH. Dantrolene sodium is a specific antagonist and should be available wherever general anesthesia is administered. Increased understanding of the clinical manifestation and pathophysiology of the syndrome, has lead to the mortality decreasing from 80 % thirty years ago to <5 % in 2006. PMID:26238698

  1. Basic and clinical aspects of malignant melanoma

    SciTech Connect

    Nathanson, L. )

    1987-01-01

    This book contains the following 10 chapters: The role of oncogenes in the pathogenesis of malignant melanoma; Laminin and fibronectin modulate the metastatic activity of melanoma cells; Structure, function and biosynthesis of ganglioside antigens associated with human tumors derived from the neuroectoderm; Epidemiology of ocular melanoma; Malignant melanoma: Prognostic factors; Endocrine influences on the natural history of human malignant melanoma; Psychosocial factors associated with prognostic indicators, progression, psychophysiology, and tumor-host response in cutaneous malignant melanoma; Central nervous system metastases in malignant melanoma; Interferon trials in the management of malignant melanoma and other neoplasms: an overview; and The treatment of malignant melanoma by fast neutrons.

  2. [Malignancies in patients on dialysis].

    PubMed

    Motán, J; Krízek, M; Fínek, J; Mukensnabl, P

    2005-01-01

    Incidence of malignancies in patients on dialysis is higher than in the comparable population. The topic is discussed from different points of view: A. Malignancy as a cause of renal failure (renal and urinary tract tumors, von Hippel-Lindau disease, Wilms tumor, multiple myeloma, tumors that compress urinary tract). B. Treatment of malignancies may result in renal failure and dialysis (nephrectomy, tumor-lysis syndrome, postradiation fibrosis, direct toxic effect of chemotherapy). C. Dialyzed patients are in higher risk of malignancies, especially those of the kidney and urinary tract but also of pharynx and larynx, thyroid gland etc. The following factors may play some roles: the basic disease, (e.g. analgesic and Balcan nephropathies, China Herba nephropathy etc.), changed metabolic milieu with retention of carcinogens, deficiency of selenium and other substances, acquired renal cysts, compromised immunity, decreased "wash-effect" in oligo-anuria and possible influence of dialysis itself (contact with phtalates, ethylenoxide, nitrosamines etc.). D. Special problems in diagnostics of malignancies. Controversial validity of s.c. "tumor markers" is mentioned. Among the causes of death in dialyzed patients cardiovascular and infectious diseases predominate. The active search for renal and urinary tract tumors should be performed. All other diagnostic procedures depend on the individual patient's risk profile. E. Methods of renal substitution are used in the treatment of malignancies (e.g. dialysis in the tumor-lysis syndrome, plasma filtration to remove paraproteins, intraperitoneal administration of chemotherapy similar to peritoneal dialysis approach). F. Malignant tumors and dialysis--some ethical problems. Withdrawal of dialysis in severely suffering patients should be approved by an informed patient and followed by maximal palliative therapy including palliative ultrafiltration if threat of lung edema occurs. PMID:16013514

  3. Recent advances in the pharmacotherapy of infantile spasms.

    PubMed

    Riikonen, Raili

    2014-04-01

    Adrenocorticotrophic hormone (ACTH), oral corticosteroids and vigabatrin are now first-line treatments for infantile spasms in the US and Europe. There is now increased knowledge regarding the role of ACTH, corticosteroids and vigabatrin (e.g. efficacy, doses, side effects, treatment in specific aetiological subtypes of infantile spasms), and other antiepileptic drugs (i.e. topiramate, valproate, zonisamide, sulthiame, levetiracetam, lamotrigine, pyridoxine, ganaxolone), as well as adjunctive flunarizine and novel drugs not yet in clinical use for infantile spasms (i.e. pulse rapamycin and melanocortin receptor agonists). The existence of a latent period, weeks to months following a precipitating brain insult, raises the possibility of preventive interventions. Recent experimental data emerging from animal models of infantile spasms have provided optimism that new and innovative treatments can be developed, and knowledge that drug treatment can affect long-term cognitive outcome is increasing. The aim of this article is to review recent developments in the pharmacotherapy of infantile spasms and to highlight the practical implications of the latest research. PMID:24504827

  4. Infantile amnesia: forgotten but not gone.

    PubMed

    Li, Stella; Callaghan, Bridget L; Richardson, Rick

    2014-03-01

    Unlike adult memories that can be remembered for many years, memories that are formed early in life are more fragile and susceptible to being forgotten (a phenomenon known as "infantile" or "childhood" amnesia). Nonetheless, decades of research in both humans and nonhuman animals demonstrate the importance of early life experiences on later physical, mental, and emotional functioning. This raises the question of how early memories can be so influential if they cannot be recalled. This review presents one potential solution to this paradox by considering what happens to an early memory after it has been forgotten. Specifically, we describe evidence showing that these forgotten early-acquired memories have not permanently decayed from storage. Instead, there appears to be a memory "trace" that persists in the face of forgetting which continues to affect a variety of behavioral responses later in life. Excitingly, the discovery of this physical trace will allow us to explore previously untestable issues in new ways, from whether forgetting is due to a failure in retrieval or storage to how memories can be recovered after extended periods of time. A greater understanding of the characteristics of this memory trace will provide novel insights into how some memories are left behind in childhood while others are carried with us, at least in some form, for a lifetime. PMID:24532837

  5. Role of connexins in infantile hemangiomas

    PubMed Central

    Blanke, Katja; Dähnert, Ingo; Salameh, Aida

    2013-01-01

    The circulatory system is one of the first systems that develops during embryogenesis. Angiogenesis describes the formation of blood vessels as a part of the circulatory system and is essential for organ growth in embryogenesis as well as repair in adulthood. A dysregulation of vessel growth contributes to the pathogenesis of many disorders. Thus, an imbalance between pro- and antiangiogenic factors could be observed in infantile hemangioma (IH). IH is the most common benign tumor during infancy, which appears during the first month of life. These vascular tumors are characterized by rapid proliferation and subsequently slower involution. Most IHs regress spontaneously, but in some cases they cause disfigurement and systemic complications, which requires immediate treatment. Recently, a therapeutic effect of propranolol on IH has been demonstrated. Hence, this non-selective ?-blocker became the first-line therapy for IH. Over the last years, our understanding of the underlying mechanisms of IH has been improved and possible mechanisms of action of propranolol in IH have postulated. Previous studies revealed that gap junction proteins, the connexins (Cx), might also play a role in the pathogenesis of IH. Therefore, affecting gap junctional intercellular communication is suggested as a novel therapeutic target of propranolol in IH. In this review we summarize the current knowledge of the molecular processes, leading to IH and provide new insights of how Cxs might be involved in the development of these vascular tumors. PMID:23596415

  6. Cyclosporin-A associated malignancy

    PubMed Central

    Durnian, Jonathan M; Stewart, Rosalind MK; Tatham, Richard; Batterbury, Mark; Kaye, Stephen B

    2007-01-01

    The use of cyclosporin is well established within the ophthalmology community, especially against sight threatening intraocular inflammation. It is well known however, that immunosuppression in general is a risk factor for the development of malignancy and numerous studies point to the risk imposed by cyclosporin. This article analyses and reviews all relevant studies with regard to the development of malignancy associated with the use of cyclosporin and extrapolates this into the ophthalmic setting. This is to enable clinicians to assess the risks in individual patients and to present a monitoring regime which can be used in patients undergoing cyclosporin treatment. The review is solely concerned with the risk of the development of malignancy following cyclosporin immunosuppression and not with any other adverse effect. PMID:19668519

  7. Decidualized Ovarian Mass Mimicking Malignancy

    PubMed Central

    Wong, Lufee; Botolahy, Vola; Carteret, Thibault; Marty, Marion; Brun, Jean-Luc

    2015-01-01

    Deciduosis classically occurs in the context of known endometriosis in the pelvis, most commonly in the ovaries, but also in the peritoneum. However, ovarian deciduosis outside the context of endometriosis is rare and makes diagnosis difficult, especially as the sonographic appearance suggests a malignant process. We report a case of decidualized ovarian mass in a patient without prior history of endometriosis that mimicked an ovarian malignancy. MRI may be a useful imaging modality to monitor these lesions and guide management. Consultation with a multidisciplinary team accustomed to such conditions will help to tailor the management to each individual. PMID:25960900

  8. Infantile Spasms: A Critical Review of Emerging Animal Models

    PubMed Central

    Stafstrom, Carl E

    2009-01-01

    Infantile spasms is a developmental epilepsy syndrome with unique clinical and EEG features, a specific pattern of pharmacological responsiveness, and poor outcome in terms of cognition and epilepsy. Despite the devastating nature of infantile spasms, little is known about its pathogenesis. Until recently, there has been no animal model available to investigate the pathophysiology of the syndrome or to generate and test novel therapies. Now, several promising animal models have emerged, spanning the etiological spectrum from genetic causes (e.g., Down syndrome or Aristaless-related homeobox [ARX] mutation) to acquired causes (e.g., endogenous and exogenous toxins or stress hormones with convulsant activity or blockade of neural activity). These new models are discussed in this review, with emphasis on the insights each can provide for understanding, treating, and preventing infantile spasms. PMID:19471616

  9. Latest American and European updates on infantile spasms.

    PubMed

    Lux, Andrew L

    2013-03-01

    Infantile spasms remain a challenging condition to study and treat, and although they form the commonest epilepsy syndrome with onset in infancy, the challenge is broadened by the wide range of potential underlying causes. The field of study remains dynamic, with debates relating to case definitions and organising structures for classification of seizures and epilepsies in general, and a newly proposed genetic and biologic classification specifically for infantile spasms. There have been recent consensus statements, a Delphi process eliciting prioritised quality-of-care indicators, systematic reviews of treatment, and a survey of clinical practice in the USA. There is increasing evidence that longer duration of spasms is associated with poorer neurodevelopmental outcomes. It has taken many years to develop an animal model that reasonably represents infantile spasms, but there are now several animal models, and they are leading to innovative and valuable studies that suggest novel treatments. PMID:23341252

  10. Visuo-vestibular eye movements: infantile strabismus in 3 dimensions.

    PubMed

    Brodsky, Michael C

    2005-06-01

    Infantile strabismus is accompanied by latent nystagmus, primary inferior oblique muscle overaction, and dissociated vertical divergence. If we examine the evolutionary underpinnings of these ocular rotations, we can construct a unifying mechanism for the sensorimotor abnormalities that arise in humans with infantile strabismus. Latent nystagmus, primary inferior oblique muscle overaction, and dissociated vertical divergence correspond to visual balancing reflexes that are operative in lateral-eyed animals in yaw, pitch, and roll, respectively. In humans with infantile strabismus, these subcortical visual reflexes are reactivated by a physiologic imbalance in binocular visual input, which resets central vestibular tone in 3-dimensional space. These visual reflexes reveal the evolutionary role of the eyes as sensory balance organs that can directly modulate central vestibular tone. Latent nystagmus, primary oblique muscle overaction, and dissociated vertical divergence should be reclassified as visuo-vestibular eye movements. PMID:15955986

  11. Cutaneous metastasis of breast carcinoma mimicking malignant melanoma in scalp

    E-print Network

    Martí, Nuria; Molina, Inmaculada; Monteagudo, Carlos; López, Verónica; García, Laura; Jordá, Esperanza

    2008-01-01

    Cutaneous metastatic carcinoma of the breast mimicking malignant melanoma,Cutaneous pigmented metastasis from breast carcinoma simulating malignant melanoma.Cutaneous metastasis of breast carcinoma mimicking malignant melanoma

  12. Nematode infection mimicking paratesticular malignancy.

    PubMed

    Kallampallil, Jins; Wood, Sarah J; O'Dempsey, Timothy; Craigie, Ross J

    2013-01-01

    Paratesticular swellings pose a diagnostic dilemma due to concerns over malignancy. We present a case of paratesticular swelling in a 13-year-old boy as a result of Dirofilaria immitis infection. The boy presented with a 2-month history of right testicular discomfort associated with an irregular mass within the scrotum. PMID:24326431

  13. Differentiation of benign and malignant

    E-print Network

    Yodh, Arjun G.

    based on large optical data sets. Images of oxy-, deoxy-, and total hemoglobin concentration as well subjects. Malignant can- cers N=41 showed statistically significant higher total hemoglobin, oxy-hemoglobin- bin, oxy-hemoglobin concentration, and scattering exhibited high area under

  14. Malignant skin melanoma in Croatia.

    PubMed

    Materljan, Eris; Zamolo, Gordana; Petkovi?, Marija; Ivosevi?, Dejan; Popovi?, Branislava; Materljan, Mauro; Katunari?, Miljenko; Jurisi?, Davor

    2009-12-01

    Global heating and increased solar ultraviolet irradiance have caused an increase in number of many diseases, particularly skin malignant diseases. Aim of this study was to investigate the influence of climate changes on the health of the population of the Primorsko-goranska and Istria Counties. We gathered and analyzed data about the frequency of skin malignant melanoma in the period of eight years (1998-2005). The data were collected from the Croatian cancer registry. The incidence of malignant skin cancer was estimated overall, by age group and gender. We found that the incidence of the skin melanoma was approximately the same in both counties during the period 1998-2005. However, significant increase has been noted when compared to the situation in the period 1977-1996 (p = 4.95 E-13) The incidence of malignant skin melanoma has risen during the last ten years. It is differently distributed between gender and age groups in Primorsko-goranska and Istria County. It can be related to climate changes, but also to different ways way of life between these two counties. PMID:20102094

  15. The Origin of Malignant Malaria

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Plasmodium falciparum is the causative agent of malignant malaria, which is among the most severe human infectious diseases. Despite its overwhelming significance to human health, the parasite’s origins remain unclear. The favored origin hypothesis holds that P. falciparum and its closest known rel...

  16. Nematode infection mimicking paratesticular malignancy

    PubMed Central

    Kallampallil, Jins; Wood, Sarah J; O'Dempsey, Timothy; Craigie, Ross J

    2013-01-01

    Paratesticular swellings pose a diagnostic dilemma due to concerns over malignancy. We present a case of paratesticular swelling in a 13-year-old boy as a result of Dirofilaria immitis infection. The boy presented with a 2-month history of right testicular discomfort associated with an irregular mass within the scrotum. PMID:24326431

  17. The genetic landscape of infantile spasms.

    PubMed

    Michaud, Jacques L; Lachance, Mathieu; Hamdan, Fadi F; Carmant, Lionel; Lortie, Anne; Diadori, Paola; Major, Philippe; Meijer, Inge A; Lemyre, Emmanuelle; Cossette, Patrick; Mefford, Heather C; Rouleau, Guy A; Rossignol, Elsa

    2014-09-15

    Infantile spasms (IS) is an early-onset epileptic encephalopathy of unknown etiology in ?40% of patients. We hypothesized that unexplained IS cases represent a large collection of rare single-gene disorders. We investigated 44 children with unexplained IS using comparative genomic hybridisation arrays (aCGH) (n = 44) followed by targeted sequencing of 35 known epilepsy genes (n = 8) or whole-exome sequencing (WES) of familial trios (n = 18) to search for rare inherited or de novo mutations. aCGH analysis revealed de novo variants in 7% of patients (n = 3/44), including a distal 16p11.2 duplication, a 15q11.1q13.1 tetrasomy and a 2q21.3-q22.2 deletion. Furthermore, it identified a pathogenic maternally inherited Xp11.2 duplication. Targeted sequencing was informative for ARX (n = 1/14) and STXBP1 (n = 1/8). In contrast, sequencing of a panel of 35 known epileptic encephalopathy genes (n = 8) did not identify further mutations. Finally, WES (n = 18) was very informative, with an excess of de novo mutations identified in genes predicted to be involved in neurodevelopmental processes and/or known to be intolerant to functional variations. Several pathogenic mutations were identified, including de novo mutations in STXBP1, CASK and ALG13, as well as recessive mutations in PNPO and ADSL, together explaining 28% of cases (5/18). In addition, WES identified 1-3 de novo variants in 64% of remaining probands, pointing to several interesting candidate genes. Our results indicate that IS are genetically heterogeneous with a major contribution of de novo mutations and that WES is significantly superior to targeted re-sequencing in identifying detrimental genetic variants involved in IS. PMID:24781210

  18. Do We Know What Causes Malignant Mesothelioma?

    MedlinePLUS

    ... Next Topic Can malignant mesothelioma be prevented? Do we know what causes malignant mesothelioma? Researchers have found ... genes – the instructions for how our cells function. We usually look like our parents because they are ...

  19. PERCEPTIONS OF RISK OF MALIGNANT MELANOMA SKIN

    E-print Network

    Bateman, Ian J.

    PERCEPTIONS OF RISK OF MALIGNANT MELANOMA SKIN CANCER FROM SUNLIGHT: A COMPARATIVE STUDY OF YOUNG OF MALIGNANT MELANOMA SKIN CANCER FROM SUNLIGHT: A COMPARATIVE STUDY OF YOUNG PEOPLE IN THE UK AND NEW ZEALAND Research Council (ESRC) ISSN 0967-8875 #12;Abstract Malignant melanoma skin cancer has been increasing

  20. Leukoplakia: A short review on malignant potential

    PubMed Central

    Masthan, K. M. K.; Babu, N. Aravindha; Sankari, S. Leena; Priyadharsini, C.

    2015-01-01

    Oral leukoplakia is one of the most common potentially malignant disorders. Right diagnosis of potentially malignant disorders may help to prevent these lesions from malignant transformation. Proper understanding, recognizing, identification and differentiating these lesions from normal mucosa are necessary for proper treatment. PMID:26015699

  1. Serous and seromucinous infantile ovarian cystadenomas--a study of 42 cases.

    PubMed

    Massicot, Richard; Rousseau, Véronique; Darwish, Ahmed A; Sauvat, Frédérique; Jaubert, Francis; Nihoul-Fékété, Claire

    2009-01-01

    The rarity of infantile ovarian cystadenoma (CA) accounts for the very little knowledge about their behaviour. The aim of this retrospective study is to highlight the modes of presentation and to evaluate the treatments and the recurrence risks of these benign tumours. Relation to adult epithelial ovarian tumours is discussed. The medical records and imaging studies of 42 CA in 31 children less than 16 years of age operated at our institution between 1985 and 2003 were retrospectively evaluated. Mean age of first surgery was 11.5 years. 7/31 girls (22.6%) presented with a bilateral CA, four of them were synchronous. 8/42 (19%) CA were in torsion at surgery, conservative management was possible in four cases. 31/42 (74%) CA were treated conservatively. 4/42 CA recurred 1-3.5 years after complete cyst removal. All were endocervical type CA, there was no intestinal type. The 42 CA were serous in 18/42, mucinous in 23/42 and unqualified in one. Mucinous epithelial cells were often sparse and focal along the cyst wall. Four CA presented with micropapillae in post-pubertal girls. No borderline tumours were observed. Mucinous cystadenomas (MCA) are better described as seromucinous cystadenoma (SMCA) because of the mucinous cells localisation. CA occurs early in life, we surmise that they may need hormonal stimulation to develop micropapillae. Complete removal of these potentially low-grade malignant ovarian tumours precursors is advocated. Conservative surgery is recommended to preserve ovarian function. PMID:18996636

  2. Alexander disease with mild dorsal brainstem atrophy and infantile spasms.

    PubMed

    Torisu, Hiroyuki; Yoshikawa, Yoko; Yamaguchi-Takada, Yui; Yano, Tamami; Sanefuji, Masafumi; Ishizaki, Yoshito; Sawaishi, Yukio; Hara, Toshiro

    2013-05-01

    We present the case of a Japanese male infant with Alexander disease who developed infantile spasms at 8 months of age. The patient had a cluster of partial seizures at 4 months of age. He presented with mild general hypotonia and developmental delay. Macrocephaly was not observed. Brain magnetic resonance imaging (MRI) findings fulfilled all MRI-based criteria for the diagnosis of Alexander disease and revealed mild atrophy of the dorsal pons and medulla oblongata with abnormal intensities. DNA analysis disclosed a novel heterozygous missense mutation (c.1154 C>T, p.S385F) in the glial fibrillary acidic protein gene. At 8 months of age, tonic spasms occurred, and electroencephalography (EEG) revealed hypsarrhythmia. Lamotrigine effectively controlled the infantile spasms and improved the abnormal EEG findings. Although most patients with infantile Alexander disease have epilepsy, infantile spasms are rare. This comorbid condition may be associated with the distribution of the brain lesions and the age at onset of Alexander disease. PMID:22818990

  3. The Organic Etiology of Infantile Autism: Myth or Fact?

    ERIC Educational Resources Information Center

    Sanua, Victor D.

    The author reviews theories and research on the etiology of infantile autism, specifically regarding its organic basis. He cites controversies over its organic vs. environmental basis and over the family's impact on autism. Quotes from such theoriests as L. Kanner, B. Bettleheim, and B. Rimland are presented along with E. R. Ritvo and M. Coleman.…

  4. Infantile Spasms and Cytomegalovirus Infection: Antiviral and Antiepileptic Treatment

    ERIC Educational Resources Information Center

    Dunin-Wasowicz, Dorota; Kasprzyk-Obara, Jolanta; Jurkiewicz, Elzbieta; Kapusta, Monika; Milewska-Bobula, Bogumila

    2007-01-01

    From 1 January 1995 to 31 December 2004, 22 patients (13 males, nine females; age range 2-12mo) with infantile spasms and cytomegalovirus (CMV) infection were treated with intravenous ganciclovir (GCV) and antiepileptic drugs. GCV was given for 3 to 12 weeks with a 1-month interval (one, two, or three courses). Epileptic spasms occurred before…

  5. Part One: Infantile Spasms--The New Consensus

    ERIC Educational Resources Information Center

    Pellock, John

    2011-01-01

    Infantile spasms (IS, West syndrome) represent a difficult to treat and sometimes not immediately recognized form of epilepsy which is relatively rare. West Syndrome or IS is one of the most recognized types of epileptic encephalopathy, a form of epilepsy usually associated with developmental regression and delay, frequently difficult to treat and…

  6. Endobronchial metastases from extrathoracic malignancies.

    PubMed

    Akoglu, Sebahat; Uçan, Eyüp S; Celik, Gülperi; Sener, Gülper; Sevinç, Can; Kilinç, O?uz; Itil, Oya

    2005-01-01

    Endobronchial metastases (EBM) from extrapulmonary malignant tumors are rare. The most common extrathoracic malignancies associated with EBM are breast, renal and colorectal carcinomas. In this study, we aimed to evaluate the clinical, radiographic and bronchoscopic aspects of patients with EBM who were diagnosed between 1992 and 2002. Data about patients' clinical conditions, symptoms, radiographic and endoscopic findings, and histopathological examination results were investigated. EBM was defined as bronchoscopically visible lesions histopathologically identical to the primary tumor in patients with extrapulmonary malignancies. We found 15 cases with EBM. Primary tumors included breast (3), colorectal (3), and renal (2) carcinomas; Malignant Melanoma (2); synovial sarcoma (1), ampulla of Vater adenocarcinoma (1), pheochromocytoma (1), hypernephroma (1), and Hodgkin's Disease (1). The most common symptoms were dyspnea (80%), cough (66.6%) and hemoptysis (33.3%). Multiple (40%) or single (13.3%) pulmonary nodules, mediastinal or hilar lymphadenopathy (40%), and effusion (40%) were the most common radiographic findings. The mean interval from initial diagnosis to diagnosis of EBM was 32.8 months (range, 0-96 months) and median survival time was 18 months (range, 4-84). As a conclusion, various extrapulmonary tumors can metastasize to the bronchus. Symptoms and radiographic findings are similar with those in primary lung cancer. Therefore, EBM should be discriminated from primary lung cancer histopathologically. Although mean survival time is usually short, long-term survivors were reported. Consequently, treatment must be planned according to the histology of the primary tumor, evidence of metastasis to other sites and medical status of the patient. PMID:16475029

  7. Skin manifestations of internal malignancy.

    PubMed

    Braverman, Irwin M

    2002-02-01

    This article concentrates on the major signs and syndromes that are associated with internal malignancies in the geriatric population. Included are cutaneous metastases, ectopic adrenocorticotropic hormone-producing syndromes, and disorders arising from APUD cell tumors. The major paraneoplastic disorders of dermatomyositis, generalized pruritus, Bazex's syndrome, and acanthosis nigricans also are discussed. Also included are Bowen's disease of skin; arsenical toxicity; and the Peutz-Jeghers', Gardner's, and Torre's syndromes, which are indicative of systemic or organ-related carcinogens. PMID:11913734

  8. Malignant cancer and invasive placentation

    PubMed Central

    D'Souza, Alaric W.; Wagner, Günter P.

    2014-01-01

    Cancer metastasis is an invasive process that involves the transplantation of cells into new environments. Since human placentation is also invasive, hypotheses about a relationship between invasive placentation in eutherian mammals and metastasis have been proposed. The relationship between metastatic cancer and invasive placentation is usually presented in terms of antagonistic pleiotropy. According to this hypothesis, evolution of invasive placentation also established the mechanisms for cancer metastasis. Here, in contrast, we argue that the secondary evolution of less invasive placentation in some mammalian lineages may have resulted in positive pleiotropic effects on cancer survival by lowering malignancy rates. These positive pleiotropic effects would manifest themselves as resistance to cancer cell invasion. To provide a preliminary test of this proposal, we re-analyze data from Priester and Mantel (Occurrence of tumors in domestic animals. Data from 12 United States and Canadian colleges of veterinary medicine. J Natl Cancer Inst 1971;47:1333-44) about malignancy rates in cows, horses, cats and dogs. From our analysis we found that equines and bovines, animals with less invasive placentation, have lower rates of metastatic cancer than felines and canines in skin and glandular epithelial cancers as well as connective tissue sarcomas. We conclude that a link between type of placentation and species-specific malignancy rates is more likely related to derived mechanisms that suppress invasion rather than different degrees of fetal placental aggressiveness. PMID:25324490

  9. From Infantile Citizens to Infantile Institutions: The Metaphoric Transformation of Political Economy in the 2008 Housing Market Crisis

    ERIC Educational Resources Information Center

    Foley, Megan

    2012-01-01

    The logic of political economy depends on a domestic metaphor, using the "oikos" or household as a model for the "polis." Historically, this metaphor has imagined citizens as the children of a paternal state. However during the 2008 housing crisis, this metaphor was turned upside down, depicting citizens as the parents of infantile state…

  10. Secretion of a truncated osteopetrosis-associated transmembrane protein 1 (OSTM1) mutant inhibits osteoclastogenesis through down-regulation of the B lymphocyte-induced maturation protein 1 (BLIMP1)-nuclear factor of activated T cells c1 (NFATc1) axis.

    PubMed

    Shin, Bongjin; Yu, Jungeun; Park, Eui-Soon; Choi, Seunga; Yu, Jiyeon; Hwang, Jung Me; Yun, Hyeongseok; Chung, Young-Ho; Hong, Kwan Soo; Choi, Jong-Soon; Takami, Masamichi; Rho, Jaerang

    2014-12-26

    Genetic mutations in osteoclastogenic genes are closely associated with osteopetrotic bone diseases. Genetic defects in OSTM1 (osteopetrosis-associated transmembrane protein 1) cause autosomal recessive osteopetrosis in humans. In particular, OSTM1 mutations that exclude the transmembrane domain might lead to the production of a secreted form of truncated OSTM1. However, the precise role of the secreted form of truncated OSTM1 remains unknown. In this study, we analyzed the functional role of truncated OSTM1 in osteoclastogenesis. Here, we showed that a secreted form of truncated OSTM1 binds to the cell surface of osteoclast (OC) precursors and inhibits the formation of multinucleated OCs through the reduction of cell fusion and survival. Truncated OSTM1 significantly inhibited the expression of OC marker genes through the down-regulation of the BLIMP1 (B lymphocyte-induced maturation protein 1)-NFATc1 (nuclear factor of activated T cells c1) axis. Finally, we demonstrated that truncated OSTM1 reduces lipopolysaccharide-induced bone destruction in vivo. Thus, these findings suggest that autosomal recessive osteopetrosis patients with an OSTM1 gene mutation lacking the transmembrane domain produce a secreted form of truncated OSTM1 that inhibits osteoclastogenesis. PMID:25359771

  11. A Case of Infantile Alexander Disease Accompanied by Infantile Spasms Diagnosed by DNA Analysis

    PubMed Central

    Lee, Jung Mu; Kim, Ae Suk; Lee, Sun Ju; Cho, Sung Min; Lee, Dong Seok; Choi, Sung Min; Ki, Chang Seok; Kim, Jong Won

    2006-01-01

    Alexander disease (AD) is a rare leukodystrophy of the central nervous system of unknown etiology. AD is characterized by progressive failure of central myelination and the accumulation of Rosenthal fibers in astrocytes, and is inevitably lethal in nature. Symptomatically, AD is associated with leukoencephalopathy with macrocephaly, seizures, and psychomotor retardation in infants, and usually leads to death within the first decade. Its characteristic magnetic resonance imaging (MRI) findings have been described as demyelination predominantly in the frontal lobe. Moreover, dominant mutations in the GFAP gene, coding for glial fibrillary acidic protein (GFAP), a principal astrocytic intermediate filament protein, have been shown to lead to AD. The disease can now be detected by genetic diagnosis. We report the Korean case of an 8-month-old male patient with AD. He was clinically characterized due to the presence of psychomotor retardation, megalencephaly, spasticity, and recurrent seizures including infantile spasms which is a remarkable presentation. Demyelination in the frontal lobe and in a portion of the temporal lobe was demonstrated by brain MRI. Moreover, DNA analysis of peripheral blood showed the presence of a R239L mutation in the GFAP gene, involving the replacement of guanine with thymine. PMID:17043438

  12. Targeted therapy in gastrointestinal malignancies

    PubMed Central

    Chhatrala, Ravi; Thanavala, Yasmin; Iyer, Renuka

    2014-01-01

    Increased understanding of cancer pathogenesis has identified several pathways that serve as potential targets for novel targeted agents in development. The selection of targeted cancer therapy based on biomarkers has instigated a new era of personalized medicine and changed the way we practice oncology. Many targeted agents are approved for treatment of gastrointestinal malignancies most targeting tumor angiogenesis, and many more are in different phases of development. Here we briefly summarize nine different targeted agents that are approved currently in the U.S. and several other agents currently being studied in various gastrointestinal cancers. PMID:24737952

  13. The psychosocial aspects of malignancy.

    PubMed

    Kriesel, H T

    1987-06-01

    This article has described many of the psychosocial issues associated with malignancy. Issues related to delivering the diagnosis of cancer, such as telling the truth, including the family, and initiating a "shared meaning" process, were considered. Patient reactions related to cancer such as grief, depression, and needs for control were described. Family reactions to the cancer patient, including anticipatory grief and weariness, were noted. The need for psychosocial support for the family of the cancer patient was discussed. Finally, the need for caregivers to pay attention to their own emotional needs was described. PMID:3299423

  14. 17q21.31 microdeletion associated with infantile spasms.

    PubMed

    Wray, Carter D

    2013-01-01

    Patients with 17q21.31 microdeletions frequently have neurologic abnormalities, especially seizures. This report is of a child with a deletion in this location who developed infantile spasms, a seizure type not specifically described in this syndrome. FISH analysis of parental blood metaphases demonstrated that the deletions occurred de novo. The deleted region encompasses the previously defined critical region for the 17q21.31 microdeletion syndrome, and includes the gene encoding for corticotropin-releasing hormone receptor 1, a protein implicated in hyperexcitability, and potentially in infantile spasms. Treatment with ACTH led to spasm cessation, consistent with its expected repression of CRH levels, which should be augmented by CRHR1 deletion, although this response was transient. PMID:23123321

  15. Osteomyelitis of Maxilla in Infantile With Periorbital Cellulitis

    PubMed Central

    Feng, Zhiqiang; Chen, Xufeng; Cao, Fengdi; Lai, Renfa; Lin, Qiang

    2015-01-01

    Abstract Infantile osteomyelitis (IO) is an uncommon and life-threatening disease that can be misdiagnosed. Early diagnosis and treatment can reduce the incidence of sequel. In this case report, we present a 25-day-old male infant with apparent edema in the entire left periorbital region. Intraorally, the edema occurred in the mucosa of the upper left alveolar region, and 2 draining fistulas with exuded yellow-white pus were present in the left alveolar region. The patient received constant monitoring after admission, and was diagnosed as IO of the maxilla with periorbital cellulitis and sepsis. He also received incision and drainage and anti-inflammatory treatment. After discharge, the patient was followed up for 3 months by phone call, but no recurrence of symptoms was found. Infantile osteomyelitis is rare in clinic. This case report reminds us of the significance of IO and provides some implications on its diagnosis and treatment. PMID:26448016

  16. Validation of the rat model of cryptogenic infantile spasms

    PubMed Central

    Chachua, Tamar; Yum, Mi-Sun; Velíšková, Jana; Velíšek, Libor

    2011-01-01

    Purpose To determine whether a new model of cryptogenic infantile spasms consisting of prenatal priming with betamethasone and postnatal trigger of spasms by N-methyl-D-aspartic acid responds to chronic ACTH treatment, and has similar EEG signature, efficacy of treatments, and behavioral impairments as human infantile spasms. Methods Rats prenatally primed with betamethasone on gestational day 15 were used. Spasms were triggered with N-methyl-D-aspartic acid between postnatal days (P) 10-15 in a single session or in multiple sessions in one subject. The expression of spasms was compared to prenatally saline-injected controls. Effects of relevant treatments (ACTH, vigabatrin, methylprednisolone, rapamycin) were determined in betamethasone-primed rats. In the rats after spasms, behavioral evaluation was performed in the open field and and elevated plus maze on P20-22. Key Findings NMDA at P10-15 (the rat “infant” period) triggers the spasms significantly earlier and in greater numbers in the prenatal betamethasone-exposed brain compared to controls. Similar to human condition, the spasms occur in clusters. Repeated trigger of spasms is associated with ictal EEG electrodecrements and interictal large-amplitude waves, a possible rat variant of hypsarrhythmia. Chronic ACTH treatment in a randomized experiment, and chronic pretreatment with methylprednisolone significantly suppress number of spasms similar to human condition. Pretreatment with vigabatrin, but not rapamycin, suppressed the spasms. Significant behavioral changes occurred following multiple bouts of spasms. Significance The model of infantile spasms has remarkable similarities with the human condition in semiology, EEG, pharmacological response, and long-term outcome. Thus, the model can be used for search of novel and more effective treatments for infantile spasms. PMID:21854372

  17. Infantile myofibroma: a firm, round plaque in an infant.

    PubMed

    Amano, Shinya; Halsey, Mark; Yasuda, Mariko; O'Donnell, Patrick; Csikesz, Courtney

    2015-01-01

    Infantile myofibroma is a rare fibromatous tumor that is variable in presentation and is frequently mistaken for hemangioma or rhabdomyosarcoma. We describe a 14-month-old male who presented with multiple, enlarging, firm lesions on the shoulder. Biopsy revealed a proliferation of small spindle cells with myxoid and hyalinized stroma infiltrating into the superficial adipose tissue. We provide a brief review of the clinical presentation, histopathologic features, management and recent advances in our understanding of this rare condition. PMID:26632798

  18. Caffey disease or infantile cortical hyperostosis: a case report.

    PubMed

    Kutty, Narayanan; Thomas, Doylene; George, Lionel; John, Thomas B

    2010-04-01

    Caffey disease or Infantile Cortical Hyperostosis (ICH) is a rare and mostly self limiting condition affecting young infants. It is characterized by acute inflammation of the periostium and the overlying soft tissue and is accompanied by systemic changes of irritability and fever. Diagnosis may be delayed as this disorder mimics a wide range of diseases including osteomyelitis, hypervitaminosis A, scurvy, bone tumors and child abuse. The emphasis here is to remind clinicians about the existence of the disease in this country. PMID:22125716

  19. [De novo malignancy following renal transplantation].

    PubMed

    Suzuki, S; Osaka, Y; Nakai, I; Yasumura, T; Omori, Y; Oka, T

    1994-11-01

    The characteristics and incidence of de novo malignancy was analyzed in 376 renal transplant recipients transplanted between April 1970 and December 1992. Malignancies developed in 21 recipients of living related donor renal allografts. The total number of malignancies was 23, with 2 patients developing 2 malignancies. The mean age at the time of diagnosis was 42 years. The average interval from transplantation to the time of diagnosis was 129 months. Malignancy developed in 12 of 21 patients who survived 10 years with a functioning graft. Nine patients died of their malignancy. The risk of developing malignancy is increased following renal transplantation. Compared with sex- and age-matched Japanese control, the incidence is 6.1 times greater for male, 10.5 times greater for female, and 7.3 times greater overall. The risk was increased at all sites except the stomach. The risk rate of acquiring malignancies at 5-year intervals following transplantation was 6.5 times greater from 0 to 5 years, 10.0 times greater from 5 to 10 years, and 9.3 times greater from 10 to 15 years. These results suggest that annual medical examinations should be performed as part of the routine log-term follow-up of renal transplant recipients to detect malignancies in the early stage. PMID:7830710

  20. B-Cell Hematologic Malignancy Vaccination Registry

    ClinicalTrials.gov

    2015-09-15

    Monoclonal Gammopathy of Undetermined Significance; Multiple Myeloma; Waldenstrom Macroglobulinemia; Lymphocytosis; Lymphoma, Non-Hodgkin; B-Cell Chronic Lymphocytic Leukemia; Hematological Malignancies

  1. Lymphocytosis, lymphadenopathy: benign or malignant?

    PubMed

    Winter, Jane N; Peterson, LoAnn C

    2015-12-01

    The increasing use of immunophenotypic and molecular analysis in the routine evaluation of patients with lymphocytosis, lymphadenopathy, or other hematologic disorders has led to the identification of unexpected small clonal lymphoid populations. These clones, sometimes with disease-specific markers, such as the t(14;18), are especially challenging for the clinician because of their unknown biologic potential and uncertain clinical behavior. Study of these early lymphoid lesions is providing important clues to the process of lymphomagenesis, and may provide the rationale for preemptive therapy in the future. More and more, the hematologist/oncologist is consulted regarding otherwise healthy individuals with lymphadenopathy and/or lymphocytosis, and pathology reports that confound the referring internist or surgeon. The report does not name a malignant lymphoproliferative disorder, but is not completely "normal". Does the patient have a benign or malignant condition? How should they be evaluated? Is treatment indicated? These patients prove challenging for the consulting hematologist as well as the referring physician. In this review, we will focus on some of these scenarios and attempt to provide guidance for their management. PMID:26637708

  2. Radioguided surgery in urological malignancies

    PubMed Central

    Weckermann, Dorothea; Thalgott, Mark; Holl, Gabriele; Wagner, Theodor; Harzmann, Rolf

    2008-01-01

    The current literature was reviewed for articles focusing on radioguided surgery in urological malignancies. In penile cancer sentinel lymph node dissection is part of international guidelines. By detailed histopathological analysis (serial sections, immunohistochemical staining) more micrometastases are detectable improving the histopathological staging. In prostate cancer this technique also improves staging since a high percentage of patients have lymph node metastases located outside the region of standard lymphadenectomy. Compared to extended lymph node dissection radioguided surgery has a lower morbidity, especially a lower rate of lymphoceles. In bladder cancer the sentinel lymph node (SLN) technique has some limitations. Combined with extended lymph node dissection more positive lymph nodes are removed which possibly improves survival. In renal cell and testicular cancer there are only preliminary results. Further investigations will show whether this technique will play an important role in the diagnostics and therapy of these tumors. In all urological malignancies the SLN concept is only a staging procedure. When the sentinel node(s) is (are) negative, the other lymph nodes are negative, too. Since there are no randomized prospective trials comparing the results of sentinel lymphadenectomy with other techniques of lymph node dissection, it is not clear whether sentinel lymph node dissection also has a prognostic impact. PMID:19468350

  3. Malignant melanoma of the skin

    PubMed Central

    Armstrong, B. K.; Holman, C. D. J.

    1987-01-01

    Ultra-violet radiation (UVR) in sunlight is thought to be the main cause of malignant melanoma in lightly-pigmented populations. Individuals with fair skin, fair hair, blue eyes and/or a tendency to burn rather than tan when exposed to the sun are at particularly high risk of melanoma and should be given special attention in primary prevention programmes. Intermittent exposure to the sun, as in recreational exposure, may be a more potent cause of melanoma than more continuous exposure. Primary prevention offers the best prospects for a substantial reduction in mortality from malignant melanoma. However, there is little evidence available to judge the effectiveness of primary prevention of melanoma through reduction of exposure to the sun. Education for reducing exposure to the sun is common in high-risk populations but has never been evaluated adequately. Mortality from melanoma could also possibly be reduced by earlier diagnosis through education or screening of high-risk groups. Regular screening of patients with the familial dysplastic naevus syndrome should reduce their mortality from melanoma. PMID:3301043

  4. Infantile spasms are associated with abnormal copy number variations.

    PubMed

    Tiwari, Vijay N; Sundaram, Senthil K; Chugani, Harry T; Huq, A H M M

    2013-10-01

    The authors tested the hypothesis that de novo copy number variations (CNVs) implicated in known genomic disorders ("pathogenic CNVs") are significant predisposing factors of infantile spasms. The authors performed a genome-wide analysis of single-nucleotide polymorphism genotyping microarray data to identify the role of de novo/known pathogenic large CNVs in 13 trios of children affected by infantile spasms. A rare, large (4.8 Mb) de novo duplication was detected in the 15q11-13 region of 1 patient. In addition, 3 known pathogenic CNVs (present in the patient as well as 1 of the parents) were detected in total. In 1 patient, a known pathogenic deletion was detected in the region of 2q32.3. Similarly, in 1 other patient, 2 known pathogenic deletions in the regions of 16p11.2 and Xp22.13 (containing CDKL5) were detected. These findings suggest that some specific pathogenic CNVs predispose to infantile spasms and may be associated with different phenotypes. PMID:22914377

  5. Linkage analysis of late-infantile neuronal ceroid-lipofuscinosis

    SciTech Connect

    Sharp, J.; Wheeler, R.B.; Jaervelae, I.

    1995-06-05

    The neuronal ceroid-lipofuscinoses (NCL) are a group of neurodegenerative disorders with an autosomal-recessive pattern of inheritance. There are 3 main categories of childhood NCL, namely, infantile, late-infantile, and juvenile NCL. These can be distinguished on the basis of age of onset, clinical course, and histopathology. A number of variant forms of NCL have also been mapped to chromosome areas 1p32 and 16p12, respectively. The gene for late-infantile NCL (LINCL), CLN2, has been excluded from both these loci, but its location is as yet unknown. Recently, CLN5, the gene for the Finnish variant form of LINCL, was mapped to 13q21.1-32. Using the 3 microsatellite markers which were most tightly linked to CLN5, we have excluded CLN2 from this region using a subset of 17 families. Thus, CLN2 represents a fourth distinct genetic locus involved in the pathogenesis of NCL. 6 refs., 1 fig., 1 tab.

  6. Vaccine Therapies in Malignant Glioma

    PubMed Central

    Oh, Taemin; Sayegh, Eli T.; Fakurnejad, Shayan; Oyon, Daniel; Lamano, Jonathan Balquiedra; DiDomenico, Joseph David; Bloch, Orin; Parsa, Andrew T.

    2015-01-01

    Glioblastoma is a grade IV astrocytoma that is widely accepted in clinical neurosurgery as being an extremely lethal diagnosis. Long-term survival rates remain dismal and, even when tumors undergo gross resection with confirmation of total removal on neuroimaging, they invariably recur with even greater virulence. Standard therapeutic modalities as well as more contemporary treatments have largely resulted in disappointing improvements. However, the therapeutic potential of vaccine immunotherapy for malignant glioma should not be underestimated. In contrast to many of the available treatments, vaccine immunotherapy is unique because it offers the means of delivering treatment that is highly specific to both the patient and the tumor. Peptide, heat-shock proteins, and dendritic cell vaccines collectively encapsulate the majority of research efforts involving vaccine-based treatment modalities. In this review, important recent findings for these vaccine types are discussed in the context of ongoing clinical trials. Broad challenges to immunotherapy are also considered. PMID:25431096

  7. Irreversible Electroporation of Hepatic Malignancy

    PubMed Central

    Narayanan, Govindarajan; Froud, Tatiana; Suthar, Rekhaben; Barbery, Katuska

    2013-01-01

    Hepatocellular carcinoma (HCC) is a worldwide problem of epidemic proportions, best treated in a multidisciplinary setting. Major advances have been made in all specialties that manage patients with HCC, with surgical options at one end of the spectrum and palliative chemotherapy on the other, and the vast majority of patients require the involvement and expertise of interventional oncology. Several ablative and transarterial technologies are currently available. Irreversible electroporation (IRE) is a new ablative technology that uses high-voltage, low-energy DC current to create nanopores in the cell membrane, disrupting the homeostasis mechanism and inducing cell death by initiating apoptosis. This article discusses the evolution of IRE as well as its safety and efficacy in the context of other ablative therapies in the treatment of hepatic malignancies. PMID:24436519

  8. [Malignant hyperthermia syndrome: case report].

    PubMed

    Taffarel, Pedro; Koffman, Fernando; Zifferman, Andrea; Degiuseppe, Sebastián; Mansilla, Alejandro; Darduin, Marcelo; Acerenza, Marcelo

    2015-04-01

    Malignant hyperthermia syndrome is a family myopathy of pharmacogenetic nature, which appears as a skeletal muscle hypercatabolic syndrome linked to anesthesia. The incidence in pediatrics is 1 event per 10 000 surgeries. The clinical picture may have a rapid onset associated with succinylcholine, or a late onset related to inhalation agents. The clinical picture includes tachycardia, hyperthermia, hypercapnia, acidosis, muscle rigidity, hyperkalemia, renal failure and arrhythmia. Mortality without specific treatment is of 80% and drops to 7% with the use of dantrolene sodium. We report an 8-year-old patient admitted for phimosis surgery; having tachycardia, hypercapnia and muscle rigidity, he started treatment with dantrolene sodium in the operating room, which was maintained for 72 hours. He evolved the first 12 hours with low cardiac output and creatine phosphokinase maximum of 155,147 U/L. He remained with mechanical ventilation for 48 hours. Discharge was given on the sixth day without sequelae. PMID:25727836

  9. Rare Malignant Tumors of the Breast

    PubMed Central

    Miller, Trevor; Albarracin, Constance; Carkaci, Selin; Whitman, Gary J; Adrada, Beatriz E

    2015-01-01

    While the more common forms of breast cancer are well understood and recognized, there are many important rare malignancies that are less appreciated. Many of these cancers have imaging findings that, when understood, help to formulate a more educated differential diagnosis. In this article, the clinical features, imaging, and pathologic findings of rare breast malignancies will be discussed. PMID:26664775

  10. Malignant gonadal tumour formation in intersexual states

    PubMed Central

    Pigott, H. W. S.

    1975-01-01

    Two cases of malignant tumour are reported in phenotypically male hermaphrodites. The importance of establishing the presence of persistent Müllerian duct structures in pseudo-hermaphrodites is discussed in relation to prophylactic castration in anticipation of malignant change. ImagesFig. 1Fig. 2 PMID:1197157

  11. Management of malignant hyperthermia: diagnosis and treatment

    PubMed Central

    Schneiderbanger, Daniel; Johannsen, Stephan; Roewer, Norbert; Schuster, Frank

    2014-01-01

    Malignant hyperthermia is a potentially lethal inherited disorder characterized by disturbance of calcium homeostasis in skeletal muscle. Volatile anesthetics and/or the depolarizing muscle relaxant succinylcholine may induce this hypermetabolic muscular syndrome due to uncontrolled sarcoplasmic calcium release via functionally altered calcium release receptors, resulting in hypoxemia, hypercapnia, tachycardia, muscular rigidity, acidosis, hyperkalemia, and hyperthermia in susceptible individuals. Since the clinical presentation of malignant hyperthermia is highly variable, survival of affected patients depends largely on early recognition of the symptoms characteristic of malignant hyperthermia, and immediate action on the part of the attending anesthesiologist. Clinical symptoms of malignant hyperthermia, diagnostic criteria, and current therapeutic guidelines, as well as adequate management of anesthesia in patients susceptible to malignant hyperthermia, are discussed in this review. PMID:24868161

  12. Gynecologic Malignancies Post-LeFort Colpocleisis

    PubMed Central

    2014-01-01

    Introduction. LeFort colpocleisis (LFC) is a safe and effective obliterative surgical option for older women with advanced pelvic organ prolapse who no longer desire coital activity. A major disadvantage is the limited ability to evaluate for post-LFC gynecologic malignancies. Methods. We present the first case of endometrioid ovarian cancer diagnosed after LFC and review all reported gynecologic malignancies post-LFC in the English medical literature. Results. This is the second reported ovarian cancer post-LFC and the first of the endometrioid subtype. A total of nine other gynecologic malignancies post-LFC have been reported in the English medical literature. Conclusions. Gynecologic malignancies post-LFC are rare. We propose a simple 3-step strategy in evaluating post-LFC malignancies. PMID:25525536

  13. Expression of Cellular Oncogenes in Human Malignancies

    NASA Astrophysics Data System (ADS)

    Slamon, Dennis J.; Dekernion, Jean B.; Verma, Inder M.; Cline, Martin J.

    1984-04-01

    Cellular oncogenes have been implicated in the induction of malignant transformation in some model systems in vitro and may be related to malignancies in vivo in some vertebrate species. This article describes a study of the expression of 15 cellular oncogenes in fresh human tumors from 54 patients, representing 20 different tumor types. More than one cellular oncogene was transcriptionally active in all of the tumors examined. In 14 patients it was possible to study normal and malignant tissue from the same organ. In many of these patients, the transcriptional activity of certain oncogenes was greater in the malignant than the normal tissue. The cellular fes (feline sarcoma) oncogene, not previously known to be transcribed in mammalian tissue, was found to be active in lung and hematopoietic malignancies.

  14. Association analysis of polymorphisms of the CRHR1 gene with infantile spasms.

    PubMed

    Yang, Guang; Zou, Li-Ping; Wang, Jing; Shi, Xiu-Yu; Yang, Xiao-Fan; Wang, Bin; Liu, Yu-Jie; Sun, Yan-Hong; Jia, Fei-Yong

    2015-08-01

    While >200 types of etiologies have been shown to be involved in the pathogenesis of infantile spasms, the pathophysiology of infantile spasms remains largely elusive. Pre-natal stress and hypothalamic-pituitary-adrenal axis dysfunction were shown to be involved in the development of infantile spasms. To test the genetic association between the CRHR1 gene, which encodes the corticotrophin-releasing hormone (CRH) receptor, and infantile spasms, five single nucleotide polymorphisms (SNPs) in the CRHR1 gene were genotyped in a sample set of 128 cases with infantile spasms and 131 healthy controls. Correlation analysis was performed on the genotyped data. Under the assumption of the dominant model, the selected five SNPs, rs4458044, rs171440, rs17689966, rs28364026 and rs242948, showed no association with the risk of infantile spasms and the effectiveness of adrenocorticotropic hormone treatment. In addition, subsequent haplotype analysis suggested none of them was associated with infantile spasms. In conclusion, the experimental results of the present study suggested no association between the CRHR1 gene and infantile spasms in a Chinese population. PMID:25954915

  15. Association analysis of polymorphisms of the CRHR1 gene with infantile spasms

    PubMed Central

    YANG, GUANG; ZOU, LI-PING; WANG, JING; SHI, XIU-YU; YANG, XIAO-FAN; WANG, BIN; LIU, YU-JIE; SUN, YAN-HONG; JIA, FEI-YONG

    2015-01-01

    While >200 types of etiologies have been shown to be involved in the pathogenesis of infantile spasms, the pathophysiology of infantile spasms remains largely elusive. Pre-natal stress and hypothalamic-pituitary-adrenal axis dysfunction were shown to be involved in the development of infantile spasms. To test the genetic association between the CRHR1 gene, which encodes the corticotrophin-releasing hormone (CRH) receptor, and infantile spasms, five single nucleotide polymorphisms (SNPs) in the CRHR1 gene were genotyped in a sample set of 128 cases with infantile spasms and 131 healthy controls. Correlation analysis was performed on the genotyped data. Under the assumption of the dominant model, the selected five SNPs, rs4458044, rs171440, rs17689966, rs28364026 and rs242948, showed no association with the risk of infantile spasms and the effectiveness of adrenocorticotropic hormone treatment. In addition, subsequent haplotype analysis suggested none of them was associated with infantile spasms. In conclusion, the experimental results of the present study suggested no association between the CRHR1 gene and infantile spasms in a Chinese population. PMID:25954915

  16. What Are the Key Statistics about Malignant Mesothelioma?

    MedlinePLUS

    ... Article Close Push escape to close saved articles window. My Saved Articles » My ACS » Malignant Mesothelioma + - Text Size Download Printable Version [PDF] » What Is Malignant Mesothelioma? TOPICS ...

  17. Metastatic malignant blue nevus: a case report.

    PubMed

    Ozgür, F; Akyürek, M; Kayikçio?lu, A; Bari?ta, I; Gököz, A

    1997-10-01

    This report presents a 63-year-old Caucasian woman with a malignant blue nevus, which is an extremely rare form of melanoma originating from or associated with a preexisting blue nevus. The background blue nevus on the left upper arm, which had been present for 5 to 6 years, increased in size and darkened in color for 3 months prior to histological diagnosis of malignant blue nevus. Although the tumor looked much like a nodular melanoma clinically, the diagnosis of malignant blue nevus was established histologically. The patient had a poor outcome due to metastatic spread of the tumor to the visceral organs 1 year following the initial excision of the tumor. To distinguish this rare tumor from other melanocytic lesions, strict histological criteria are needed to make the diagnosis of malignant blue nevus. Differential diagnosis includes cellular blue nevus, atypical cellular blue nevus, primary malignant melanoma, and metastatic melanoma to the dermis. Malignant blue nevus is most commonly seen on the scalp. The tumor has an aggressive behavior and metastasizes in the majority of patients. This paper describes the second reported case of malignant blue nevus involving the upper arm. Clinical and histological features of this uncommon tumor are presented, along with a review of the literature. PMID:9339284

  18. Surgical Treatments for Infantile Purulent Meningitis Complicated by Subdural Effusion

    PubMed Central

    Wang, Xianshu; Zhang, Xiaoru; Cao, Hongbin; Jing, Shiyuan; Yang, Zhiguo; Cheng, Zhenghai; Liu, Ye; Li, Xin; Gao, Feifei; Ji, Yuanqi

    2015-01-01

    Background Infantile purulent meningitis (PM) is a commonly severe intracranial infectious disease in infants under age 1 year. In recent years, several diagnostic and treatment methods were reported, but in these cases the neurological complications and sequel were often observed, among which subdural effusion (SE) is the most common complication in PM. Timely diagnosis and early intervention are vital for better outcomes. In this study, the surgical treatments for infantile PM complicated by SE were investigated. Material/Methods Patients who had PM complicated by SE in the Children’s Hospital of Hebei Province from June 2000 to June 2012 were retrospectively analyzed and 170 patients were enrolled in the study. Surgical treatment for each patient was adopted according to producing effusion time, leucocyte count, protein content, intracranial pressure, and bacteria culture, coupled with cranial ultrasound examination, CT, and MRI scans. Results Nearly, 15 patients were cured using serial taps, with a 50% cure rate. Seventeen out of 30 (56.6%) patients receiving subcutaneous reservoir drainage had better outcome. Nearly 80% of patients (55/69) who underwent minimally invasive trepanation and drainage were positive. Surgical procedure of minimally invasive trepanation and drainage combined with drug douche was effective in 63% of patients (19/30). In addition, 6 patients were cured with subdural-peritoneal shunt. Only 1 patient died, after the recurrence of meningitis, and the remaining 4 patients were cured by craniotomy. Conclusions For infantile PM complicated with SE, treatment needs be chosen according to the specific situation. Surgical procedure of minimally invasive trepanation and drainage is a very effective treatment in curing PM complicated by SE. The treatment was highly effective with the use of drug douche. Subdural-peritoneal shunt and craniotomy were as effective as in refractory cases. PMID:26482715

  19. Clinical Characteristics and Treatment Options of Infantile Vascular Anomalies

    PubMed Central

    Yang, Bin; Li, Li; Zhang, Li-xin; Sun, Yu-juan; Ma, Lin

    2015-01-01

    Abstract To analyze the clinical characteristics and treatment outcomes of vascular anomalies, and determine which therapy is safe and effective. The data of vascular anomalies pediatric patients who arrived at Beijing children's Hospital from January 2001 to December 2014 were analyzed retrospectively, including the influence of gender, age, clinical manifestation, diagnosis, treatment options, and outcomes. As to infantile hemangiomas, the outcomes of different treatments and their adverse reactions were compared. As to spider angioma and cutaneous capillary malformation, the treatment effect of 595?nm pulsed dye laser (PDL) is analyzed. A total number of 6459 cases of vascular anomalies were reclassified according to the 2014 ISSVA classification system. Among them, the gender ratio is 1:1.69, head-and-neck involved is 53.3%, the onset age within the first month is 72.4%, the age of initial encounter that younger than 6 months is 60.1%. The most common anomalies were infantile hemangiomas (42.6%), congenital hemangiomas (14.1%), and capillary malformations (29.9%). In treating infantile hemangiomas, laser shows the lowest adverse reactions rate significantly. Propranolol shows a higher improvement rate than laser, glucocorticoids, glucocorticoids plus laser, and shows no significant difference with propranolol plus laser both in improvement rate and adverse reactions rate. The total improvement rate of 595?nm PDL is 89.8% in treating spider angioma and 46.7% in treating cutaneous capillary malformation. The improvement rate and excellent rate of laser in treating cutaneous capillary malformation are growing synchronously by increasing the treatment times, and shows no significant difference among different parts of lesion that located in a body. Vascular anomalies possess a female predominance, and are mostly occurred in faces. Definite diagnosis is very important before treatment. In treating infantile hemangioma, propranolol is recommended as the first-line agent, and systemic use glucocorticoids should be considered when associated with serious complications. The 595?nm PDL is effective in managing superficial vascular malformations in childhood, and could attempt to increase the treatment times to improve the outcomes. PMID:26448027

  20. Infantile Systemic Hyalinosis: Report of 17-year Experience

    PubMed Central

    Raeeskarami, Seyed Reza; Aghighi, Yahya; Afshin, Azadeh; Malek, Abdolreza; Zamani, Ali; Ziaee, Vahid

    2014-01-01

    Background: Infantile Systemic Hyalinosis (ISH) is a very rare autosomal recessive disorder characterized by connective tissue involvement as hyaline deposition in skin, gastrointestinal tract, muscles, glands and other organs. Cases Presentation: We report eight Iranian children (4 male and 4 female) with ISH referred to our hospital from 1996 to 2013. The illness had been diagnosed by clinical manifestations and disease progression. Six of them died and two are alive but very sick. Conclusion: ISH is a very rare disorder with poor prognosis. Seventy five percent of our 8 patients died before 2 years old due to severe diarrhea, malabsorption and/or infection. PMID:26019786

  1. Review of topical beta blockers as treatment for infantile hemangiomas.

    PubMed

    Painter, Sally L; Hildebrand, Göran Darius

    2016-01-01

    The treatment of infantile hemangiomas changed from the use of oral corticosteroids to oral propranolol on the serendipitous discovery of propanolol's clinical effectiveness in 2008. Since then, clinicians have begun to use topical beta blockers-in particular, timolol maleate 0.5% gel forming solution-with good effect. Topical beta blockers are now used for lesions with both deep and superficial components and those that are amblyogenic. When initiated in the proliferative phase of the lesion, the effectiveness of the treatment can be seen within days. There is no consensus on dosing, treatment bioavailability, or clinical assessment of lesions, but these are topics for future research. PMID:26408055

  2. Una Mirada al Cáncer Infantil y Los Hispanos

    Cancer.gov

    El cáncer infantil es poco común—los niños con cáncer representan menos de 1% de todos los casos nuevos de cáncer en Estados Unidos. Pero, ¿sabía usted que el cáncer es la segunda causa principal de muerte (después de accidentes) en los niños de 1 a 14 años de edad? Se calculó que en 2012, en Estados Unidos, más de 12 000 niños (de recién nacidos¬ a 14 años de edad) serían diagnosticados con cáncer y más de 1300 niños morirían por esta enfermedad.

  3. Infantile hydrocephalus: a review of epidemiology, classification and causes

    PubMed Central

    Tully, Hannah M; Dobyns, William B

    2015-01-01

    Hydrocephalus is a common but complex condition caused by physical or functional obstruction of CSF flow that leads to progressive ventricular dilatation. Though hydrocephalus was recently estimated to affect 1.1 in 1,000 infants, there have been few systematic assessments of the causes of hydrocephalus in this age group, which makes it a challenging condition to approach as a scientist or as a clinician. Here, we review contemporary literature on the epidemiology, classification and pathogenesis of infantile hydrocephalus. We describe the major environmental and genetic causes of hydrocephalus, with the goal of providing a framework to assess infants with hydrocephalus and guide future research. PMID:24932902

  4. Canine olfactory detection of malignant melanoma

    PubMed Central

    Campbell, Leon Frederick; Farmery, Luke; George, Susannah Mary Creighton; Farrant, Paul B J

    2013-01-01

    Our patient is a 75-year-old man who presented after his pet dog licked persistently at an asymptomatic lesion behind his right ear. Examination revealed a nodular lesion in the postauricular sulcus. Histology confirmed malignant melanoma, which was subsequently excised. Canine olfactory detection of human malignancy is a well-documented phenomenon. Advanced olfaction is hypothesised to explain canine detection of bladder, breast, colorectal, lung, ovarian, prostate and skin cancers. Further research in this area may facilitate the development of a highly accurate aid to diagnosis for many malignancies, including melanoma. PMID:24127369

  5. Malignant Mesothelioma Diagnosed by Bronchoscopic Biopsy

    PubMed Central

    Park, Yeon-Hee; Choi, Jae-Woo; Jung, Sang-Ok; Cho, Min-Ji; Kang, Da-Hyun; Chung, Chae-Uk; Park, Dong-Il; Moon, Jae-Young; Park, Hee-Sun; Jung, Sung-Soo; Kim, Ju-Ock; Kim, Sun-Young

    2015-01-01

    Malignant mesothelioma is a rare malignant neoplasm that arises from mesothelial surfaces of the pleural cavity, peritoneal cavity, tunica vaginalis, or pericardium. Typically, pleural fluid cytology or closed pleural biopsy, surgical intervention (video thoracoscopic biopsy or open thoracotomy) is conducted to obtain pleural tissue specimens. However, endobronchial lesions are rarely seen and cases diagnosed from bronchoscopic biopsy are also rarely reported. We reported the case of a 77-year-old male who was diagnosed as malignant mesothelioma on bronchoscopic biopsy from obstructing masses of the endobronchial lesion. PMID:26175790

  6. Insulinoma with focal hepatic lesions: malignant insulinoma?

    PubMed

    Jerraya, Hichem; Zidi-Mouaffek, Yossra; Dokmak, Safi; Dziri, Chadli

    2015-01-01

    Insulinoma is a rare tumour that is malignant in only 10% of cases. We report a case of insulinoma in a 59-year-old woman, associated with focal liver lesions, which raised the suspicion of malignancy of a pancreatic tumour. Enucleation of the insulinoma was performed with wedge resection of one hepatic nodule. Pathological examination indicated that the pancreatic tumour was compatible with insulinoma whereas the hepatic lesion was related to focal nodular hyperplasia. This clinical case highlights the need for histopathological proof of malignancy before selecting therapeutic strategies for insulinomas. PMID:26670896

  7. Improved radioimmunotherapy of hematologic malignancies

    SciTech Connect

    Press, O.W.

    1992-03-24

    This research project proposes to develop novel new approaches of improving the radioimmunodetection and radioimmunotherapy of malignancies by augmenting retention of radioimmunoconjugates by tumor cells. The approaches shown to be effective in these laboratory experiments will subsequently be incorporated into out ongoing clinical trials in patients. Specific project objectives include: to study the rates of endocytosis, intracellular routing, and metabolic degradation of radiolabeled monoclonal antibodies targeting tumor-associated antigens on human leukemia and lymphoma cells; To examine the effects of lysosomotropic amines (e.g. chloroquine, amantadine), carboxylic ionophores (monensin, nigericin), and thioamides (propylthiouracil), on the retention of radiolabeled MoAbs by tumor cells; to examine the impact of newer radioiodination techniques (tyramine cellobiose, paraiodobenzoyl) on the metabolic degradation of radioiodinated antibodies; to compare the endocytosis, intracellular routing, and degradation of radioimmunoconjugates prepared with different radionuclides ({sup 131}Iodine, {sup 111}Indium, {sup 90}Yttrium, {sup 99m}Technetium, {sup 186}Rhenium); and to examine the utility of radioimmunoconjugates targeting oncogene products for the radioimmunotherapy and radioimmunoscintigraphy of cancer.

  8. Novel immunotherapies in lymphoid malignancies.

    PubMed

    Batlevi, Connie Lee; Matsuki, Eri; Brentjens, Renier J; Younes, Anas

    2016-01-01

    The success of the anti-CD20 monoclonal antibody rituximab in the treatment of lymphoid malignancies provided proof-of-principle for exploiting the immune system therapeutically. Since the FDA approval of rituximab in 1997, several novel strategies that harness the ability of T cells to target cancer cells have emerged. Reflecting on the promising clinical efficacy of these novel immunotherapy approaches, the FDA has recently granted 'breakthrough' designation to three novel treatments with distinct mechanisms. First, chimeric antigen receptor (CAR)-T-cell therapy is promising for the treatment of adult and paediatric relapsed and/or refractory acute lymphoblastic leukaemia (ALL). Second, blinatumomab, a bispecific T-cell engager (BiTE(®)) antibody, is now approved for the treatment of adults with Philadelphia-chromosome-negative relapsed and/or refractory B-precursor ALL. Finally, the monoclonal antibody nivolumab, which targets the PD-1 immune-checkpoint receptor with high affinity, is used for the treatment of Hodgkin lymphoma following treatment failure with autologous-stem-cell transplantation and brentuximab vedotin. Herein, we review the background and development of these three distinct immunotherapy platforms, address the scientific advances in understanding the mechanism of action of each therapy, and assess the current clinical knowledge of their efficacy and safety. We also discuss future strategies to improve these immunotherapies through enhanced engineering, biomarker selection, and mechanism-based combination regimens. PMID:26525683

  9. Novel immunotherapies for hematological malignancies

    PubMed Central

    Nelson, Michelle H.; Paulos, Chrystal M.

    2014-01-01

    Summary The immune system is designed to discriminate between self and tumor tissue. Through genetic recombination, there is fundamentally no limit to the number of tumor antigens that immune cells can recognize. Yet, tumors use a variety of immunosuppressive mechanisms to evade immunity. Insight into how the immune system interacts with tumors is expanding rapidly and has accelerated the translation of immunotherapies into medical breakthroughs. Herein, we appraise the state of the art in immunotherapy with a focus on strategies that exploit the patient’s immune system to kill cancer. We review various forms of immune-based therapies, which have shown significant promise in patients with hematological malignancies, including (i) conventional monoclonal therapies like rituximab, (ii) engineered monoclonal antibodies called bispecific T cell engagers (BiTEs), (iii) monoclonal antibodies and pharmaceutical drugs that block inhibitory T-cell pathways (i.e. PD-1, CTLA-4 and IDO), and (iv) adoptive cell transfer (ACT) therapy with T cells engineered to express chimeric antigen receptors (CARs) or T-cell receptors (TCRs). We also assess the idea of using these therapies in combination and conclude by suggesting multi-prong approaches to improve treatment outcomes and curative responses in patients. PMID:25510273

  10. Malignancy in Noonan syndrome and related disorders.

    PubMed

    Smpokou, P; Zand, D J; Rosenbaum, K N; Summar, M L

    2015-12-01

    Noonan syndrome (NS) and related disorders, such as NS with multiple lentigines (formerly called LEOPARD syndrome), cardiofaciocutaneous syndrome, and Costello syndrome, constitute an important group of developmental malformation syndromes with variable clinical and molecular features. Their underlying pathophysiologic mechanism involves dysregulation of the Ras/mitogen-activated protein kinase signaling pathway, an essential mediator of developmental and growth processes in the prenatal and postnatal setting. Malignant tumor development is an important complication encountered in other RASopathies, such as neurofibromatosis type 1, but the neoplastic risks and incidence of malignant tumors are less clearly defined in NS and related disorders of the Noonan spectrum. Malignant tumor development remains an important complication variably seen in the RASopathies and, thus, a clear understanding of the underlying risks is essential for appropriate clinical care in this patient population. This review discusses previously published reports of malignancies in individuals with RASopathies of the Noonan spectrum. PMID:25683281

  11. Young Cancer Survivors Often Develop New Malignancies

    MedlinePLUS

    ... fullstory_155005.html Young Cancer Survivors Often Develop New Malignancies Teens, young adults who received radiation treatment ... risk for other cancers later in life, a new study reveals. Researchers analyzed U.S. National Cancer Institute ...

  12. Toward automated detection of malignant melanoma

    E-print Network

    Gareau, Daniel S.

    In vivo reflectance confocal microscopy shows promise for the early detection of malignant melanoma (MM). Two hallmarks of MM have been identified: the presence of pagetoid melanocytes in the epidermis and the breakdown ...

  13. New developments in surgery of malignant gliomas

    PubMed Central

    Vranic, Andrej

    2011-01-01

    Background Malignant gliomas account for a high proportion of brain tumours. With new advances in neurooncology, the recurrence-free survival of patients with malignant gliomas has been substantially prolonged. It, however, remains dependent on the thoroughness of the surgical resection. The maximal tumour resection without additional postoperative deficit is the goal of surgery on patients with malignant gliomas. In order to minimize postoperative deficit, several pre- and intraoperative techniques have been developed. Conclusions Several techniques used in malignant glioma surgery have been developed, including microsurgery, neuroendoscopy, stereotactic biopsy and brachytherapy. Imaging and functional techniques allowing for safer tumour resection have a special value. Imaging techniques allow for better preoperative visualization and choice of the approach, while functional techniques help us locate eloquent regions of the brain. PMID:22933950

  14. The Role of PTEN in Myeloid Malignancies

    PubMed Central

    Panuzzo, Cristina; Crivellaro, Sabrina; Carrà, Giovanna; Torti, Davide; Guerrasio, Angelo; Saglio, Giuseppe

    2015-01-01

    PTEN deletion in the mouse and in the zebrafish highlights the essential role of this tumor suppressor in the development of myeloid malignancies, in particular acute myeloid leukemia and myeloproliferative disorders. In humans, extensive genetic sequences of myeloid malignancies did not reveal recurrent PTEN mutations and deletions. However, PTEN was shown to be functionally inactivated in several acute myeloid leukemia and chronic myeloid leukemia samples, through both post-trasductional modifications, changes in protein levels and cellular compartmentalization. Notably, non genomic inactivation of PTEN in myeloid malignancies could represent a challenging therapeutic opportunity for these diseases. Targeting those mechanisms that affect PTEN function could indeed promote PTEN reactivation with consequent cancer selective apoptosis induction. In this review we will describe the role of PTEN in the development of myeloid malignancies.

  15. Transgenic mouse model for skin malignant melanoma.

    PubMed

    Kato, M; Takahashi, M; Akhand, A A; Liu, W; Dai, Y; Shimizu, S; Iwamoto, T; Suzuki, H; Nakashima, I

    1998-10-01

    We report here on a novel metallothionein-I (MT)/ret transgenic mouse line in which skin melanosis, benign melanocytic tumor and malignant melanoma metastasizing to distant organs develop stepwise. The process of tumor development and its malignant transformation in this line may resemble that of the human giant congenital melanocytic nevus that is present at birth and that frequently gives rise to malignant melanoma during aging. We observed an increase in the expression level and activity of the ret transgene during the disease progression. That increase in transgene expression accompanied an activation of mitogen-activated protein kinases (MAPKs) and c-Jun as well as matrix metalloproteinases. These results suggest that progressive dysregulation of the expression level of the ret transgene might play a crucial role in the malignant transformation of melanocytic tumors developed in the MT/ret transgenic mouse line. PMID:9778055

  16. Malignant mesothelioma: Canadian perspective and research directions

    PubMed Central

    Lee, C.W.; Martin, J.; MacRae, R.; Tsao, M.S.; Nguyen, E.; Johnston, M.; Baas, P.; Laurie, S.; Feld, R.; Murray, N.; Shepherd, F.A.

    2008-01-01

    Since the 1960s, the incidence of malignant mesothelioma in Canada has increased dramatically because of work-related asbestos exposures. Treatment options are limited. Although chemotherapy is now an accepted standard in the management of advanced disease, uncertainty surrounds the roles of radical surgery and radiation. In March 2007, a symposium was held in Vancouver, B.C., to review the current approach to malignant mesothelioma in Canada and to discuss development of a national clinical research strategy.

  17. Quality-of-care indicators for infantile spasms.

    PubMed

    Wang, C Jason; Jonas, Rinat; Fu, Chong Min; Ng, Chun Y; Douglass, Laurie

    2013-01-01

    We developed a comprehensive set of quality-of-care indicators for the management of children with infantile spasms in the United States, encompassing evaluation, diagnosis, treatment, and prevention and management of side effects and comorbidities. The indicators were developed using the RAND/UCLA Modified Delphi Method. After a focused review of the literature and guidelines by the study team, an expert panel (nominated by leaders of Child Neurology Society, American Epilepsy Society, and National Institute for Neurologic Disorders) rated the draft indicators anonymously, met face-to-face to discuss each indicator, and rerated the revised indicators on validity, feasibility, and importance. The panel recommended 21 indicators, of which 8 were identified as most likely to have a large positive impact on improving quality of life and/or health outcomes for children with infantile spasms. The proposed indicators can be used to assess and document variations and gaps in quality-of-care and inform future research and quality improvement interventions. PMID:22566712

  18. Protective effect of probiotics in the treatment of infantile eczema

    PubMed Central

    LIN, RONG-JUN; QIU, LI-HUA; GUAN, REN-ZHENG; HU, SU-JUAN; LIU, YING-YING; WANG, GUANG-JUN

    2015-01-01

    The aim of the present study was to provide evidence for the application of probiotics in the prevention and treatment of infantile eczema by exploring changes in the intestinal Bifidobacteria levels and the Scoring Atopic Dermatitis (SCORAD) index prior and subsequent to treatment with probiotics in infants with eczema. A total of 40 infants with eczema were randomly divided into treatment and control groups. Prior and subsequent to the treatment, the SCORAD index was evaluated and the content of Bifidobacterium bifidum in the stool of each infant in the two groups was quantified using 16S rRNA/DNA quantitative polymerase chain reaction analysis. After four weeks of treatment with B. bifidum triple viable capsules, the levels of B. bifidum increased sharply (P<0.05) and the SCORAD index was notably reduced (P<0.05) as compared with the values prior to treatment. By contrast, neither the content of B. bifidum nor the SCORAD index changed significantly in the control group after four weeks (P>0.05). Following treatment, the levels of B. bifidum in the stools of the treatment group were significantly higher than those in the stools of the control group (P<0.05), and the SCORAD index was significantly lower than that of the control group (P<0.05). In conclusion, probiotic supplementation has a positive effect on the prevention and treatment of infantile eczema. PMID:26136864

  19. Malignant melanoma as second malignant neoplasm in long-term childhood cancer survivors: a systematic review.

    PubMed

    Braam, Katja I; Overbeek, Annelies; Kaspers, Gertjan J L; Ronckers, Cecile M; Schouten-van Meeteren, Annette Y N; Van Dulmen-Den Broeder, Eline; Veening, Margreet A

    2012-05-01

    This systematic review provides information on malignant melanoma as second malignant neoplasm (SMN) after childhood cancer and evaluates its risk factors. Study reports describing incidences of SMN and malignant melanoma as SMN in a population of childhood cancer survivors (CCS) were included. Of 151,575 CCS, 4,010 (2.6%) children developed an SMN, 212 of which were melanoma (5.3% or 0.14% of all CCS). The following risk factors for malignant melanoma as SMN were identified: radiotherapy, or the combination alkylating agents and anti-mitotic drugs. Melanomas are most frequently observed after Hodgkin disease, hereditary retinoblastoma, soft tissue sarcoma, and gonadal tumors. PMID:22232079

  20. Incidence and Overall Survival of Malignant Ameloblastoma

    PubMed Central

    Rizzitelli, Alexandra; Smoll, Nicolas R.; Chae, Michael P.; Rozen, Warren M.; Hunter-Smith, David J.

    2015-01-01

    Background Malignant ameloblastoma, comprising metastasizing ameloblastoma and ameloblastic carcinoma, represents 1.6–2.2% of all odontogenic tumors. Due to its rare nature, malignant ameloblastoma has only been reported in the literature in small case series or case reports. Using the Surveillance, Epidemiology and End-Results (SEER) database, we have performed a population-based study to determine the incidence rate and the absolute survival of malignant ameloblastoma. Method Using the International Classification of Diseases for Oncology (ICD-O) codes 9310/3 and 9270/3, data from the SEER database were used to calculate the incidence rate and absolute survival rate of population with malignant ameloblastoma. Results The overall incidence rate of malignant ameloblastoma was 1.79 per 10 million person/year. The incidence rate was higher in males than females and also higher in black versus white population. The median overall survival was 17.6 years from the time of diagnosis and increasing age was associated with a statistically significant poorer survival. Conclusions To our best knowledge, we report the largest population-based series of malignant ameloblastoma. The incidence rate was 1.79 per 10 million person/year and the overall survival was 17.6 years. PMID:25692490

  1. Definitions of Single and Subsequent Primaries for Hematologic Malignancies

    Cancer.gov

    While it is recognized that some malignancies occur predominantly (or even exclusively) in liquid or solid form, because so many malignancies can potentially arise as either leukemias or lymphomas (or both), all hematopoietic malignancies are assumed to have this potential. 2. Malignancies of the lymphoid series are considered to be different from those of the myeloid series.

  2. Infantile fibrosarcoma of ethmoid sinus, misdiagnosed as an adenoid in a 5-year-old child

    PubMed Central

    Geramizadeh, Bita; Khademi, Bijan; Karimi, Mehran; Shekarkhar, Golsa

    2015-01-01

    Infantile fibrosarcoma of head and neck is rare and the presence of this tumor in ethmoid sinus is even more uncommon. To the best of our knowledge, <5 cases have been reported in the last 20 years in the English literature, so far, only one of which has been infantile type in a 15 months old girl. In this case report, we will explain our experience with a rare case of infantile fibrosarcoma originating from ethmoid sinus in a 5-year-old boy who presented with dyspnea and epistaxis. After biopsy, it was diagnosed as fibrosarcoma of sinus origin. PMID:26604519

  3. Collecting and Storing Malignant, Borderline Malignant Neoplasms, and Related Samples From Young Patients With Cancer

    ClinicalTrials.gov

    2015-11-12

    Acute Undifferentiated Leukemia; Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative; Childhood Acute Lymphoblastic Leukemia; Childhood Acute Myeloid Leukemia/Other Myeloid Malignancies; Childhood Chronic Myelogenous Leukemia; Chronic Lymphocytic Leukemia; Hairy Cell Leukemia; Juvenile Myelomonocytic Leukemia; Mast Cell Leukemia; Neoplasm of Uncertain Malignant Potential; Prolymphocytic Leukemia; Secondary Acute Myeloid Leukemia; T-cell Large Granular Lymphocyte Leukemia; Unspecified Childhood Solid Tumor, Protocol Specific

  4. Vigabatrin and mental retardation in tuberous sclerosis: infantile spasms vs focal seizures

    PubMed Central

    Yum, Mi-Sun; Lee, Eun Hye; Ko, Tae-Sung

    2013-01-01

    Tuberous sclerosis complex is a genetic disorder resulting in epilepsy and mental retardation. Vigabatrin has shown efficacy in the treatment of infantile spasms caused by tuberous sclerosis complex, but its effects on focal seizures caused by tuberous sclerosis complex have not been determined. We compared the efficacy of vigabatrin in patients with tuberous sclerosis complex-induced focal seizures and infantile spasms and assessed the mental outcomes in both groups. We retrospectively evaluated 31 children with tuberous sclerosis complex and epilepsy, who were treated with vigabatrin in single tertiary center in Seoul, Korea. Vigabatrin treatment resulted in spasms cessation in 16 of 18 (88.9%) patients with infantile spasms, whereas 6 of 13 (46.2%) patients with focal seizures became seizure-free. Initial response to vigabatrin had no effect on intellectual disability. Vigabatrin was highly effective in eliminating infantile spasms caused by tuberous sclerosis complex, but was less effective in patients with focal seizures. PMID:22752486

  5. Adrenocorticotropic hormone versus prednisolone in the treatment of infantile spasms post vigabatrin failure.

    PubMed

    Jones, Kevin; Snead, O Carter; Boyd, Jennifer; Go, Cristina

    2015-04-01

    The Child Neurology Society/American Academy of Neurology practice parameter has recommended adrenocorticotropic hormone or vigabatrin in the short-term treatment of infantile spasms. When vigabatrin is unavailable or ineffective and adrenocorticotropic hormone is not a treatment option because of the prohibitive cost, other forms of corticosteroids have been considered in the treatment of infantile spasms. This retrospective study reviewed the Hospital for Sick Children's experience with the short-term effectiveness of prednisolone versus adrenocorticotropic hormone in patients with infantile spasms who have failed vigabatrin. The results showed that while adrenocorticotropic hormone was more likely to lead to short-term spasm freedom, there was no difference in the likelihood of longer-term spasm resolution without relapse. These findings can guide clinicians in the treatment of infantile spasms post vigabatrin failure. PMID:24965788

  6. Topiramate and Adrenal Cortico-tropic Hormone as Initial Treatment of Infantile Spasms

    PubMed Central

    Peltzer, Bradley; Alonso, William D.; Porter, Brenda E.

    2009-01-01

    Historically, adrenal cortico-tropic hormone (ACTH) was used as first line treatment for infantile spasms, however there has been increasing use of topiramate as initial therapy. Here we report a retrospective study of ACTH and topiramate as initial treatment of infantile spasms. The neurology patient database at the Children's Hospital of Philadelphia was searched using the ICD-9 code for infantile spasms, and 50 patients were randomly chosen for chart review. We identified thirty-one patients receiving either ACTH or topiramate monotherapy (ACTH, n = 12, topiramate n = 19) as a first line treatment for infantile spasms. Twenty-six patients were symptomatic and five cryptogenic. Six patients treated with ACTH had resolution of clinical spasms and hypsarrhithmia within a month, but three relapsed. Four of the nineteen patients treated with topiramate eventually, though over a period of 0,1,8 or 69 months, had resolution of spasms and hypsarrhythmia. PMID:19225138

  7. Vigabatrin and mental retardation in tuberous sclerosis: infantile spasms versus focal seizures.

    PubMed

    Yum, Mi-Sun; Lee, Eun Hye; Ko, Tae-Sung

    2013-03-01

    Tuberous sclerosis complex is a genetic disorder resulting in epilepsy and mental retardation. Vigabatrin has shown efficacy in the treatment of infantile spasms caused by tuberous sclerosis complex, but its effects on focal seizures caused by tuberous sclerosis complex have not been determined. We compared the efficacy of vigabatrin in patients with tuberous sclerosis complex-induced focal seizures and infantile spasms and assessed the mental outcomes in both groups. We retrospectively evaluated 31 children with tuberous sclerosis complex and epilepsy, who were treated with vigabatrin in a single tertiary center in Seoul, Korea. Vigabatrin treatment resulted in spasms cessation in 16 of 18 (88.9%) patients with infantile spasms, whereas 6 of 13 (46.2%) patients with focal seizures became seizure free. Initial response to vigabatrin had no effect on intellectual disability. Vigabatrin was highly effective in eliminating infantile spasms caused by tuberous sclerosis complex but was less effective in patients with focal seizures. PMID:22752486

  8. The Effects of Leptin Antagonist on Hypothalamic Neuropeptide Y Circuitry in Infantile Male Lambs. 

    E-print Network

    Bedenbaugh, Michelle

    2012-04-16

    It is proposed that leptin signaling during infantile development is critical for structural organization of hypothalamic circuitry involved in the control of food intake and energy expenditure. The present study tested the hypothesis...

  9. Secondary Malignancy Risk Following Proton Radiation Therapy

    PubMed Central

    Eaton, Bree R.; MacDonald, Shannon M.; Yock, Torunn I.; Tarbell, Nancy J.

    2015-01-01

    Radiation-induced secondary malignancies are a significant, yet uncommon cause of morbidity and mortality among cancer survivors. Secondary malignancy risk is dependent upon multiple factors including patient age, the biological and genetic predisposition of the individual, the volume and location of tissue irradiated, and the dose of radiation received. Proton therapy (PRT) is an advanced particle therapy with unique dosimetric properties resulting in reduced entrance dose and minimal to no exit dose when compared with standard photon radiation therapy. Multiple dosimetric studies in varying cancer subtypes have demonstrated that PRT enables the delivery of adequate target volume coverage with reduced integral dose delivered to surrounding tissues, and modeling studies taking into account dosimetry and radiation cell biology have estimated a significantly reduced risk of radiation-induced secondary malignancy with PRT. Clinical data are emerging supporting the lower incidence of secondary malignancies after PRT compared with historical photon data, though longer follow-up in proton treated cohorts is awaited. This article reviews the current dosimetric and clinical literature evaluating the incidence of and risk factors associated with radiation-induced secondary malignancy following PRT. PMID:26636040

  10. The accessory optic system: the fugitive visual control system in infantile strabismus.

    PubMed

    Brodsky, Michael C

    2012-08-01

    Infantile strabismus inaugurates a constellation of dissociated eye movements that correspond to visuovestibular reflexes in lateral-eyed animals. These visual reflexes are generated by subcortical visual pathways that use binocular visual input to modulate central vestibular tone. In this article, I present evidence that the accessory optic system is uniquely suited to provide an innervational substrate for visuovestibular eye movements in humans with infantile strabismus. PMID:22893078

  11. Ghost infantile vertebrae and hemipelves within adult skeleton from thorotrast administration in childhood.

    PubMed

    Teplick, J G; Head, G L; Kricun, M E; Haskin, M E

    1978-12-01

    In 2 adults who had received thorotrast intravenously at ages 2 and 3 years, respectively, radiopaque outlines of their infantile vertebrae were seen in the adult vertebrae. Similar "ghosts" of the hemipelves were present in the pelvis of 1 patient. Autopsy findings and autoradiographs in 1 patient strongly suggest that persisting thorotrast deposits in the infantile vertebrae and pelvis have produced a chronic radiation osteitis and dense thickened bone trabeculae, which are more radiopaque than the surrounding adult bone. PMID:725040

  12. Model of cryptogenic infantile spasms after prenatal corticosteroid priming

    PubMed Central

    Velíšek, Libor; Chachua, Tamar; Yum, Mi-Sun; Poon, Ka-Lai; Velíšková, Jana

    2010-01-01

    Infantile spasms (IS) is a devastating epilepsy syndrome of childhood. They occur in 3-12 month old infants and are characterized by spasms, interictal EEG hypsarrhythmia and profound mental retardation. Hormonal therapy (ACTH, corticosteroids) are frequently used, their efficacy is however tainted by severe side effects. For research of novel therapies, a validated animal model of IS is required. We propose the model of spastic seizures triggered by NMDA in infant rats prenatally exposed to betamethasone. The spasms have remarkable similarity to human IS, including motor flexion spasms, ictal EEG electrodecrement, and responsiveness to ACTH. Interestingly, the spasms do not involve the hippocampus. Autoradiographic metabolic mapping as well as tagging the areas of neuronal excitation with c-fos indicate a strong involvement of hypothalamic structures such as the arcuate nucleus, which has significant bilateral connections with other hypothalamic nuclei as well as with the brainstem. PMID:20618421

  13. [The infantile sexual seduction: revolution and aftermath of Freud's theory].

    PubMed

    Figueroa, Gustavo C

    2014-01-01

    There is no question about the negative effects of child sexual abuse. Freud's seduction theory asserts that psychoneuroses in adults are caused by reactivation of forgotten recollections of gross sexual abuse (involving the genitals) that had taken place prior to the age of 8 to 10 years. His contribution consisted in the discovery of specific events, prior to puberty, which were indispensable to the formation of psychoneuroses. If an adult patient recalled an infantile sexual experience, Freud assumed the interference of a pervert: a child was sexually innocent unless it had been traumatized. But Freud's technique of clinical exploration had not attained adequate reliability and was not immune to prejudices. Freud himself dropped his mechanical, static theory that presupposed a single type of accidentally occurring trauma prior to puberty, allowing him to develop his new drive and fantasy theory. PMID:24861119

  14. Expression of p16 protein in infantile hemangioma

    PubMed Central

    WANG, SHI; ZHENG, WEI

    2015-01-01

    The present study aimed to investigate the expression and significance of p16 in the occurrence, development and regression of infantile hemangioma (IH). The expression of p16 was examined in proliferating, involuting hemangioma and normal tissues using immunohistochemical techniques. The expression of p16 was significantly lower in proliferating hemangioma than in involuting hemangioma, and was significantly lower in the involuting hemangioma than in normal tissues. Significant differences were found between the three groups (P<0.05). The results indicate that p16 may be important in the regression of IH endothelial cells and in anti-angiogenesis. There is a certain association between p16 expression and the regression of hemangioma. This provides a theoretical basis for the further study of the pathological mechanisms of p16 in hemangioma and potential gene therapies that may treat this disease.

  15. Rare association of central pontine myelinolysis with infantile tremor syndrome.

    PubMed

    Datta, Kalpana; Datta, Supratim; Dutta, Indranil

    2012-01-01

    Central pontine myelinolysis (CPM) is an acute demyelination within the central basis pontis. Though exact mechanism is not known it is seen commonly with rapid correction of hyponatremia and also with pontine ischemia or infarction, demyelinating diseases, pontine neoplasm and different metabolic diseases. We report a rare association of CPM in a patient of Infantile Tremor Syndrom (ITS). ITS is a syndrome of tremor, mental and physical retardation, pigmentary changes of hair and skin and anemia in malnourished children. Though first reported in Indian subcontinent many identical cases were reported from around the world. Our case is a 15 month old child with generalized tremor, mild hepatosplenomegaly with features of grade II malnutrition including skin and hair changes. All the signs and symtoms of tremor improved after treatment with the World Health Organization (WHO) protocol for protein energy malnutrition (PEM) and administration of propranolol without any side effects. PMID:22412274

  16. Placental transfer of and infantile exposure to perchlorate.

    PubMed

    Zhang, Tao; Ma, Yufang; Wang, Dou; Li, Rudan; Chen, Xiaojia; Mo, Weiwen; Qin, Xiaolei; Sun, Hongwen; Kannan, Kurunthachalam

    2016-02-01

    Fetuses and infants are vulnerable to perchlorate toxicity. We assessed fetal and infantile exposure to perchlorate in two Chinese cities (Nanchang and Tianjin). Perchlorate was widely found (82%-100%) in breast milk, dissolved infant formula, infants' urine, maternal and cord blood samples. Perchlorate levels in infants' urine (mean ± standard deviation: 22.4 ± 35.6 ng mL(-1)), breast milk (36.6 ± 48.1 ng mL(-1)), and cord blood (3.18 ± 3.83 ng mL(-1)) samples collected from Nanchang and Tianjin were approximately an order of magnitude higher than those reported for the U.S. Perchlorate concentrations in cord blood were comparable to that in maternal blood, indicating that perchlorate is transferred from mother to fetus through placenta. Among all infants providing urine samples, the average daily intake of perchlorate (DOSEU) was estimated to be 1.17 ± 1.57 ?g kg(-1) bw d(-1), and 40% of these infants had DOSEU exceeding the RfD (0.7 ?g kg(-1) bw d(-1)) recommended by U.S. EPA. However, approximately 70% of exclusively breast-fed infants had perchlorate exposure dose via breast milk exceeding the RfD. For breast-fed infants, breast milk was the overwhelmingly predominant exposure pathway; while infant formula and indoor dust ingestion were major perchlorate exposure sources for formula-fed infants. To our knowledge, this is the first report to assess the fetal and infantile exposure to perchlorate in China. PMID:26432537

  17. Detection of global DNA hypomethylation of peripheral blood lymphocytes in patients with infantile spasms.

    PubMed

    Yang, Guang; Wang, Jing; Shi, Xiu-Yu; Yang, Xiao-Fan; Ju, Jun; Liu, Yu-Jie; Li, Zhi-Fang; Li, Yu-Fen; Zou, Li-Ping

    2015-01-01

    The pathogenesis of infantile spasms remains unclear. DNA methylation may play a pivotal role in the development of some types of neurological diseases, such as epilepsy. In this study, we aimed to investigate the relationship between global DNA methylation of peripheral blood leukocytes and cryptogenic infantile spasms. DNA from peripheral blood leukocytes was extracted from 20 patients with cryptogenic infantile spasms and 20 gender and age matched healthy controls. Global DNA methylation percentage of peripheral blood leukocytes was measured using a global DNA methylation quantification kit. Global DNA methylation levels of peripheral blood lymphocytes in patients with cryptogenic infantile spasms (23.4 ± 20.0%) were significantly lower than those in healthy controls (46.8 ± 8.4%). Furthermore, we did not find any association between the levels of DNA methylation and effectiveness of Adrenocorticotropic hormone treatment. Our study demonstrates that global DNA hypomethylation of peripheral blood lymphocytes is correlated with infantile spasms. This finding provides information for better understanding of the pathogenesis of infantile spasms. PMID:25524839

  18. [Elderly patient with cerebellar malignant astrocytoma].

    PubMed

    Kawai, Hideya; Ishikawa, Tatsuya; Moroi, Junta; Hanyu, Noriaki; Sawada, Motofumi; Kobayashi, Norikata; Mutou, Tatsuji; Hikichi, Kentaro; Suzuki, Akifumi; Yasui, Nobuyuki; Yoshida, Yasuji

    2008-09-01

    Malignant cerebellar astrocytoma is very rare and the prognosis is extremely poor. We report herein the case of an elderly patient with malignant cerebellar astrocytoma. This 80-year-old man initially presented with dizziness and ataxia of the right hand. Metastatic cerebellar tumor was diagnosed on first admission, based on a past history of colon cancer treated by surgery and magnetic resonance imaging (MRI) findings supporting the diagnosis of metastasis. The patient underwent gamma knife surgery (20 Gy) and was discharged. Follow-up after discharge was insufficient. Two years after gamma knife surgery, he returned to our hospital complaining of dizziness, headache, and right limb ataxia. MRI revealed a cystic mass in the right cerebellar hemisphere, and the lesion was removed by right suboccipital craniotomy. The tumor represented malignant astrocytoma. Optimal management of patients harboring sush difficult. to-treat tumors, including the role of gamma-knife radiosurgery, is discussed. PMID:18800635

  19. Primary tubercular mastitis masquerading as malignancy

    PubMed Central

    Prathima, S.; Kalyani, R.; Parimala, S.

    2014-01-01

    The significance of primary tubercular mastitis is due to rare occurrence and often overlooked and misdiagnosed as pyogenic breast abscess or malignancy. Despite the high incidence of tuberculosis in India, reports of breast tuberculosis among the total number of mammary conditions varies between 0.64% and 3.59%. We report a case of a 35-year-old lady with breast lump of 3 months duration, which simulated malignancy on clinical examination but fine needle aspiration cytology revealed granulomatous mastitis secondary to tuberculosis. High level of suspicion and simple fine needle aspiration procedure with micro-biological tests will clinch the final diagnosis. PMID:24678224

  20. Cutaneous Manifestations of Internal Malignant Disease

    PubMed Central

    McLean, David I.

    1987-01-01

    The skin can provide clues to the well-being of our patients. Some skin changes, such as hypertrichosis lanuginosa acquisita or erythema gyratum repens, are so specific that there is a virtual certainty of internal malignancy. Other changes, such as severe pruritus, are significant management problems in late-stage lymphoma and leukemia. Still others, such as herpes zoster in a cancer patient in remission, may be a marker for recurrent malignant disease. This review will discuss many of the skin changes associated with systemic cancer. ImagesFigure 1Figure 2Figure 3Figure 4Figure 5 PMID:21263960

  1. Malignant Melanoma Arising in Red Tattoo Ink.

    PubMed

    Joyce, Cormac Weekes; Duff, Gerald; McKenna, Dermot; Regan, Padraic James

    2015-07-01

    We report the case of a 33-year-old male who presented with a malignant melanoma on his anterior chest wall. The lesion was only found in the red ink pigment of the tattoo, as were several in-transit dermal metastases. Possible explanations include a pre-existing lesion which was seeded with red ink or the possibility of the red ink causing an inflammatory reaction leading to malignant transformation. This is the first reported case of a melanoma developing in the red ink pigment of a multi-colored tattoo. PMID:26217569

  2. [In vitro reconstruction of malignant melanoma].

    PubMed

    Lugassy, C; Escande, J P

    1987-01-01

    It is report here that three dimensional melanocytic tumors may be reconstituted when adding collagen to the cells harvested during the under covering lattice culture of malignant melanoma explants (cutaneous metastasis). The cells issued from these rebuilt malignant melanoma may be used following the same methods. Thus, the serial making of melanocytic tumors becomes possible. The problem of the relation between cellular differentiation and invasive potential of the cells may be studied using as an original model the rebuilt tumors and the cellular population which are issued from them. PMID:3121142

  3. Malignant Melanoma Arising in Red Tattoo Ink

    PubMed Central

    Duff, Gerald; McKenna, Dermot; Regan, Padraic James

    2015-01-01

    We report the case of a 33-year-old male who presented with a malignant melanoma on his anterior chest wall. The lesion was only found in the red ink pigment of the tattoo, as were several in-transit dermal metastases. Possible explanations include a pre-existing lesion which was seeded with red ink or the possibility of the red ink causing an inflammatory reaction leading to malignant transformation. This is the first reported case of a melanoma developing in the red ink pigment of a multi-colored tattoo. PMID:26217569

  4. Localized malignant pleural mesothelioma with renal metastasis

    PubMed Central

    Zardawi, Sarah Jane; Li, Bob T.; Zauderer, Marjorie G.; Wang, Jennifer W.; Atmore, Bryn B.; Barnes, Tristan A.; Pavlakis, Nick; Mathur, Manu N.; Clarke, Stephen

    2015-01-01

    Localized malignant pleural mesothelioma (LMM) is a rare subset of malignant pleural mesothelioma. Its epidemiology, biology, natural history and optimal treatment are poorly understood. We report a case of LMM treated aggressively with complete surgical resection and adjuvant radiotherapy, but subsequently complicated by local chest wall recurrence and solitary metastasis to the kidney. This case is examined in the context of a small number of cases of LMM in the literature to emphasize the existence of this rare disease entity, their unusual biological behaviour and the need for further tumour molecular and genomic research. PMID:25988069

  5. Hyperparathyroidism After Irradiation for Childhood Malignancy

    SciTech Connect

    McMullen, Todd; Bodie, Greg; Gill, Anthony; Ihre-Lundgren, Catharina; Shun, Albert; Bergin, Mary; Stevens, Graham; Delbridge, Leigh

    2009-03-15

    Purpose: To examine the occurrence of hyperparathyroidism in a cohort of patients undergoing combined parathyroid and thyroid surgery after previous head-and-neck irradiation for childhood malignancy. Methods and Materials: This is a retrospective cohort study for the years 1996 to 2007. The study group comprised patients undergoing surgery in University of Sydney Endocrine Surgical Unit who had received previous head-and-neck irradiation in childhood and who were identified as having pathologic thyroid and parathyroid characteristics. Results: A total of 53 patients were identified in whom head-and-neck irradiation for the treatment of childhood malignancy had been documented. In each of the cases, thyroid disease was the primary reason for referral for surgery. Five of these patients (10%) were found to exhibit coexisting hyperparathyroidism. The latency period for hyperparathyroidism was less than 20 years in 4 of the 5 cases. There were four conventional parathyroid adenomas and one parathyroid lipoadenoma. All patients exhibited a significant decrease in postoperative calcium levels after surgery. Conclusions: To our knowledge, this is the first study to document the significant risk of hyperparathyroidism after radiation exposure for childhood malignancy. The timeframe for development of disease is much shorter than that published for individuals who have undergone irradiation for benign diseases. High doses of therapeutic radiation at a young age make childhood survivors of malignancy at especially high risk for developing hyperparathyroidism.

  6. Hereditary costovertebral dysplasia with malignant cerebral tumour.

    PubMed Central

    David, T J; Glass, A

    1983-01-01

    Costovertebral dysplasia comprises multiple malformations of the vertebrae and ribs, with a characteristic clinical picture of short trunk dwarfism, short neck, scoliosis, and rib cage deformity. We describe two sibs with the syndrome who are presumed to represent the autosomal recessive form of the disorder. One sib died from a malignant cerebral tumour and the association may be more than fortuitous. Images PMID:6655670

  7. Attacking malignant cells that survive therapy

    PubMed Central

    Hodge, James W; Kwilas, Anna; Ardiani, Andressa; Gameiro, Sofia R

    2013-01-01

    We have recently defined “immunogenic modulation,” a mechanism whereby malignant cells that survive anticancer therapy, due to sublethal delivery or development of treatment resistance, become nonetheless more sensitive to killing by cytotoxic T lymphocytes. This mechanism can be exploited to identify which therapies will best synergize with immunotherapy, potentially maximizing patient clinical benefit. PMID:24498561

  8. Malignant solitary fibrous tumor involving the liver.

    PubMed

    Jakob, Manuel; Schneider, Matthias; Hoeller, Ingo; Laffer, Urban; Kaderli, Reto

    2013-06-01

    Solitary fibrous tumors are predominantly benign and are most commonly found in the thoracic cavity and pleura; while reports exist in the literature of malignant solitary fibrous tumors and those located in extrathoracic organs, these cases are considered extremely rare. Herein, a case is reported of a malignant solitary fibrous tumor involving the liver that was diagnosed and treated in a 62-year-old woman. The patient presented with complaints of upper abdominal pain and unintentional weight loss. Computed tomography scan of the abdomen revealed a remarkably large mass, measuring 15 cm × 10 cm × 20 cm, which appeared to be unrelated to any particular organ. The intraoperative finding of a wide communication with the left liver suggested hepatic origin, and served as an indicator for tumor resection via left hemihepatectomy. The diagnosis of solitary fibrous tumor and its malignant nature was confirmed by histological and immunohistochemical examination of the resected tissues. Hepatic solitary fibrous tumor is very rare, and surgery remains the mainstay of treatment. Due to limited reports of such tumors in the literature, little can be said about the benefit of adjuvant therapy and prognosis for the rare cases with malignant histological findings. PMID:23745040

  9. Malignant solitary fibrous tumor involving the liver

    PubMed Central

    Jakob, Manuel; Schneider, Matthias; Hoeller, Ingo; Laffer, Urban; Kaderli, Reto

    2013-01-01

    Solitary fibrous tumors are predominantly benign and are most commonly found in the thoracic cavity and pleura; while reports exist in the literature of malignant solitary fibrous tumors and those located in extrathoracic organs, these cases are considered extremely rare. Herein, a case is reported of a malignant solitary fibrous tumor involving the liver that was diagnosed and treated in a 62-year-old woman. The patient presented with complaints of upper abdominal pain and unintentional weight loss. Computed tomography scan of the abdomen revealed a remarkably large mass, measuring 15 cm × 10 cm × 20 cm, which appeared to be unrelated to any particular organ. The intraoperative finding of a wide communication with the left liver suggested hepatic origin, and served as an indicator for tumor resection via left hemihepatectomy. The diagnosis of solitary fibrous tumor and its malignant nature was confirmed by histological and immunohistochemical examination of the resected tissues. Hepatic solitary fibrous tumor is very rare, and surgery remains the mainstay of treatment. Due to limited reports of such tumors in the literature, little can be said about the benefit of adjuvant therapy and prognosis for the rare cases with malignant histological findings. PMID:23745040

  10. Malignant Solitary Fibrous Tumor of the Pancreas.

    PubMed

    Estrella, Jeannelyn S; Wang, Huamin; Bhosale, Priya R; Evans, Harry L; Abraham, Susan C

    2015-08-01

    Solitary fibrous tumor (SFT) arising in the pancreas is exceedingly rare, with only 11 cases reported in the English literature. All cases described thus far have exhibited benign histology. We report the first case of malignant SFT of the pancreas. The patient was a 52-year-old woman who presented with obstructive jaundice and a 15-cm pancreatic head mass. The mass showed areas with typical histologic features for SFT including small fibroblastlike cells arranged in the well-characterized "patternless pattern" of architecture, hemangiopericytomalike vessels, areas with dense collagen and infrequent mitoses (0-2 per 10 high-power fields [HPFs]). In addition, multiple areas with an overtly sarcomatous morphology were present, containing large spindle and epithelioid cells with nuclear pleomorphism, marked cellularity, up to17 mitoses per 10 HPFs, and necrosis. Immunohistochemical stains were positive for CD34 and B-cell CLL/lymphoma 2 (Bcl-2) in both benign and malignant components and showed strong, diffuse p53 and p16 staining in the malignant component. At last follow-up (40 months), the patient was alive and well without evidence of disease. However, given that the presence of a malignant component in extrapancreatic SFT has been associated with recurrence/metastasis and death, complete surgical resection and close long-term follow-up is required. PMID:26166470

  11. Dental health of survivors of malignant disease.

    PubMed Central

    Welbury, R R; Craft, A W; Murray, J J; Kernahan, J

    1984-01-01

    A full dental examination on 64 children aged from 3 to 20 years who were in long term remission from malignant disease showed normal facial growth, caries incidence, and periodontal indices. There was increased incidence of hypodontia and hypoplasia which in some could be ascribed to the original disease or its treatment. Images Figure PMID:6524952

  12. Sindbis viral vectors target hematopoietic malignant cells.

    PubMed

    Suzme, R; Tseng, J-C; Levin, B; Ibrahim, S; Meruelo, D; Pellicer, A

    2012-11-01

    Sindbis viral vectors target and inhibit the growth of various solid tumors in mouse models. However, their efficacy against blood cancer has not been well established. Here, we show that Sindbis vectors infect and efficiently trigger apoptosis in mouse BW5147 malignant hematopoietic T-cells, but only at low levels in human lymphoma and leukemia cells (Jurkat, Karpas, CEM, DHL and JB). The Mr 37/67?kD laminin receptor (LAMR) has been suggested to be the receptor for Sindbis virus. However, JB cells, which are infected by Sindbis at low efficiency, express high levels of LAMR, revealing that additional factors are involved in Sindbis tropism. To test the infectivity and therapeutic efficacy of Sindbis vectors against malignant hematopoietic cells in vivo, we injected BW5147 cells intraperitoneally into (C3HXAKR) F1 hybrid mice. We found that Sindbis vectors targeted the tumors and significantly prolonged survival of tumor-bearing mice. We also tested the Sindbis vectors in a transgenic CD4-Rgr model, which spontaneously develop thymic lymphomas. However, infectivity in this model was less efficient. Taken together, these results demonstrate that Sindbis vectors have the potential to target and kill hematopoietic malignancies in mice, but further research is needed to evaluate the mechanism underlining the susceptibility of human lymphoid malignancies to Sindbis therapy. PMID:22956041

  13. MRI findings in infants with infantile spasms after neonatal hypoxic-ischemic encephalopathy

    PubMed Central

    Dawn, Gano; Sargent, Michael A.; Miller, Steven P.; Connolly, Mary B.; Wong, Peter; Glass, Hannah C.; Poskitt, Kenneth J.; Chau, Vann

    2014-01-01

    Background To evaluate the predominant pattern of brain injury and the anatomic areas of injury in children with infantile spasms following neonatal hypoxic-ischemic encephalopathy (HIE). Methods A nested case-control study of infantile spasms in children with term neonatal HIE was performed. All patients had T1/T2-weighted magnetic resonance imaging (MRI) with diffusion-weighted imaging (DWI) performed on the third day of life. Using a validated scoring system, the MRI was classified as: normal, watershed, basal ganglia/thalamus, total, or focal-multifocal. Two study investigators scored additional anatomic areas of injury (cortical extent, levels of the brainstem, hypothalamus) on T1/T2-weighted MRI and DWI blinded to the outcome. The predominant pattern of brain injury and anatomic areas of injury were compared between patients who developed infantile spasms and randomly selected controls. Results Eight patients who developed infantile spasms were identified among a cohort of 176 term newborns with HIE (4.5%). There were no significant differences in the perinatal and neonatal course between newborns who developed infantile spasms and controls who did not. The development of infantile spasms after neonatal HIE was significantly associated with basal ganglia/thalamus and total brain injury (P=.001), extent of cortical injury greater than 50% (odds ratio [OR]=11.7, 95% confidence interval [CI]=1.1-158.5, P=.01), injury to the midbrain (OR=13, 95% CI=1.3 to 172, P=.007) and hypothalamic abnormalities (P=.01). Conclusions The development of infantile spasms after HIE is associated with injury to the basal ganglia and thalami on neonatal MRI, particularly when extensive cortical injury and/or injury to the midbrain is present. PMID:24095571

  14. Clinical profile and treatment of infantile spasms using vigabatrin and ACTH - a developing country perspective

    PubMed Central

    2010-01-01

    Background Infantile spasms represent a serious epileptic syndrome that occurs in the early infantile age. ACTH and Vigabatrin are actively investigated drugs in its treatment. This study describes the comparison of their efficacy in a large series of patients with infantile spasms from Pakistan. Methods All patients with infantile spasms who presented to Aga Khan University Hospital, Karachi, Pakistan from January, 2006 to April, 2008 were included in this study. Inclusion criteria were clinical symptoms of infantile spasms, hypsarrythmia or modified hyparrythmia on electroencephalography, at least six months of follow-up period and receipt of any of the two drugs mentioned above. The type of drug distribution was random according to the availability, cost and ease of administration. Results Fifty six cases fulfilled the inclusion criteria. 62.5% were males. Mean age at onset of seizures was 5 ± 1.4 months. Fifty two (92.8%) patients demonstrated hypsarrythmia on electroencephalography. 64.3% cases were identified as symptomatic while 19.6% were cryptogenic and 16.1% were idiopathic. Eighteen patients received ACTH while 38 patients received Vigabatrin as first line therapy. Initial response to first line therapy was similar (50% for ACTH and 55.3% for Vigabatrin). Overall, the symptomatic and idiopathic groups responded better to Vigabatrin. The relapse rate was higher for ACTH as compared to Vigabatrin (55.5% vs. 33.3%) when considering the first line therapy. Four patients evolved to Lennox-Gastaut variant; all of these patients had initially received Vigabatrin and then ACTH. Conclusion Vigabatrin and ACTH showed no significant difference in the initial treatment of infantile spasms. However, patients receiving ACTH were 1.2 times more likely to relapse as compared to the patients receiving Vigabatrin when considering monotherapy. We suggest that Vigabatrin should be the initial drug of choice in patients presenting with infantile spasms. However, larger studies from developing countries are required to validate the therapeutic trends observed in this study. PMID:20078871

  15. Hypercalcemia of malignancy and new treatment options

    PubMed Central

    Sternlicht, Hillel; Glezerman, Ilya G

    2015-01-01

    Hypercalcemia of malignancy affects up to one in five cancer patients during the course of their disease. It is associated with both liquid malignancies, commonly multiple myeloma, leukemia, and non-Hodgkins lymphoma and solid cancers, particularly breast and renal carcinomas as well as squamous cell carcinomas of any organ. The clinical manifestations of hypercalcemia are generally constitutional in nature and not specific to the inciting malignancy. Such physical manifestations can range from malaise to lethargy and confusion. Constipation and anorexia are common. Acute kidney injury is likely the most frequently encountered manifestation of end organ damage. Symptomatology is closely linked to both the absolute elevation of serum calcium levels and the rapidity of calcium rise. The majority of cases are humoral in etiology and related to parathyroid hormone-related protein (PTHrP). Approximately 20% of cases are the result of direct bone metastasis with extra-renal 1,25-dihydroxyvitamin D (calcitriol) and ectopic parathyroid hormone production likely accounting for less than 1% of cases. The diagnosis of hypercalcemia of malignancy is confirmed either by an elevated PTHrP or by an evidence of bone metastasis in the appropriate clinical setting. Treatment is predicated on the patient’s symptoms and absolute serum calcium level. Interventions are aimed at lowering the serum calcium concentration by inhibiting bone resorption and increasing urinary calcium excretion, the former accomplished via bisphosphonate therapy and the latter with aggressive hydration. Novel therapies for refractory disease include denosumab, a monoclonal antibody against the receptor activator of nuclear factor ?B ligand, and the calcimimetic cinacalcet. Finally, anti-PTHrP antibodies have been successfully deployed in animal models of disease. Despite the efficacy of the above therapies, hypercalcemia of malignancy portends an ominous prognosis, indicating advanced and often refractory cancer with survival on the order of months. PMID:26675713

  16. What's New in Malignant Mesothelioma Research and Treatment?

    MedlinePLUS

    ... Next Topic Additional resources for malignant mesothelioma What’s new in malignant mesothelioma research and treatment? There is ... that has shown promise in some studies. Other new drugs have different targets. For example, some new ...

  17. Malignant transformation of oral potentially malignant disorders in males: a retrospective cohort study

    PubMed Central

    2009-01-01

    Background Oral squamous cell carcinoma could be preceded by clinically evident oral potentially malignant disorders (OPMDs). Transformation of OPMDs to cancer has been studied in several population groups. It is difficult to undertake comparisons across populations due to variations in the methods of computation of malignancy rates among different studies. The aim of our study was to estimate the rate of malignant transformation of OPMDs taking into account the duration of follow-up and to identify the significant factors indicative of malignant potential. Methods A total of 148 male patients with OPMDs were included. They were selected among all consecutive subjects registered at the maxillofacial clinic at a medical hospital in Kaohsiung, Taiwan. The mean follow up period was 37.8 months. Results The malignant transformation rate was highest in subjects diagnosed with oral epithelial dysplasia. In this group the transformation rate was 7.62 per 100 persons-year. The rate in the group with verrucous hyperplasia (VH) was 5.21 per 100 persons-year, and in those with hyperkeratosis or epithelial hyperplasia was 3.26 per 100 persons-year. The anatomical site of OPMDs was the only statistically significant variable associated with malignancy. The hazard rate ratio (HRR) was 2.41 times for tongue lesions when compared with buccal lesions. Conclusion The reported discrepancies of malignant transformation of OPMDs involve the follow-up time to cancer development and hence it is preferable to use a time-to-event estimation for comparisons. We found that malignant transformation of OPMDs involving the tongue was significantly higher than in other anatomical subsites after adjusting for the clinicopathological type or lifestyle factors at diagnosis. PMID:19640311

  18. Electrochemotherapy with Cisplatin: Clinical Experience in Malignant Melanoma Patients1

    E-print Network

    Ljubljana, University of

    Electrochemotherapy with Cisplatin: Clinical Experience in Malignant Melanoma Patients1 Gregor cisplatin adminis- tration on cutaneous tumor nodules in malignant melanoma patients. In 10 patients, 133 that electrochemotherapy with cisplatin is a highly effective approach for treatment of cutaneous malignant melanoma

  19. Endemic characteristics of infantile visceral leishmaniasis in the People’s Republic of China

    PubMed Central

    2013-01-01

    Background Visceral leishmaniasis (VL) was once a severe parasitic disease in China. Thanks to the great efforts of integrated control, VL was eliminated in most epidemic areas, except for certain western provinces (autonomous region) at the end of 1950s. From then on, VL gained less attention and has seemed to spread, especially in the last 15?years. Infants are the most important population threatened by VL. However, there have been few studies on the endemic characteristics of infantile VL in China. Methods Infantile VL cases were collected from the online National Infectious Diseases Reporting System (NIDRS). Statistical description and inference was used to reveal the endemic characteristics in gender, age group, time and regionalism. Spatial analysis was carried out to explore the high risk area for infantile VL in China. Results A total of 1093 infantile VL cases were reported from 2006 to 2012. There was no statistically significant difference in gender over time. The minimum, maximum and mean age of these cases was 1.1, 35.9 and 13.8?months, respectively. Among them 86.92% were under 2?years of age, and there was a statistically significant difference among age groups over time. An incidence peak appeared in 2008-2009, most cases were distributed in the months September to December, and there was a tail-raising effect in the coming two months of the next year. More than 98% of cases were reported in Xinjiang Uygur Autonomous Region, Gansu Province and Sichuan Province, accounting for 61.02%, 32.75% and 4.57%, respectively. A total of 56 counties reported infantile VL cases, with the cumulative incidence ranging from 0.02 to 24.57%. There were two main zones of high endemicity for infantile VL in China. The monthly incidence clearly coincides with the number of towns where infantile VL cases were reported. Three fatalities were reported during the study period, the case fatality rate was 2.75‰. Conclusions The endemic situation of infantile VL is serious, and there are several active foci of infantile VL prevalence in China. VL has emerged as a severe threat to infants of endemic regions in China. PMID:23680411

  20. Safety and Efficacy of Vigabatrin for the Treatment of Infantile Spasms

    PubMed Central

    Faulkner, Michele A.; Tolman, Justin A.

    2011-01-01

    In 2009, vigabatrin became the first FDA approved medication for the treatment of infantile spasms in the United States. There are few well-designed prospective studies comparing the drug to placebo or other modalities used in the treatment of infantile spasms. The available data have demonstrated that vigabatrin is efficacious in the treatment of infantile spasms regardless of underlying etiology, but that it is particularly beneficial in patients with a diagnosis of tuberous sclerosis. Adrenocorticotropic hormone (ACTH), the only other medication with robust efficacy data, has been used as first line therapy for infantile spasms associated with other etiologies, and in general controls spasms sooner than vigabatrin, though relapse is common with both therapies. Vigabatrin is generally well tolerated. However, use has been associated with permanent loss of peripheral vision in some patients. In children with tuberous sclerosis, vigabatrin should be considered as initial therapy for infantile spasms. It is a viable alternative for patients with suboptimal response, contraindications or intolerance to ACTH. PMID:23861649

  1. The relation of infantile spasms, tubers, and intelligence in tuberous sclerosis complex

    PubMed Central

    O'Callaghan, F; Harris, T; Joinson, C; Bolton, P; Noakes, M; Presdee, D; Renowden, S; Shiell, A; Martyn, C; Osborne, J

    2004-01-01

    Background: The aetiology of the learning difficulty in tuberous sclerosis is debated. It may be related to the amount of tubers in the brain or caused by the infantile spasms that occur in early life. Aims: To examine the relative contributions to final intelligence (IQ) made by both cerebral tubers and infantile spasms. Methods: As part of an epidemiological study of tuberous sclerosis in the south of England, patients were recruited who were able to undergo magnetic resonance imaging (MRI) without the need for an anaesthetic. Epilepsy history was determined by interview and review of clinical records. IQ was assessed using either Wechsler intelligence scales or Raven's matrices. Results: A total of 41 patients consented to have an MRI scan. IQ scores were normally distributed about a mean of 91. Twenty six patients had a positive history of epilepsy, and 11 had suffered from infantile spasms. There was a significant relation between the number of tubers and IQ. Infantile spasm status partly confounded the relation between tubers and IQ, but did not render the relation statistically insignificant. The relation between infantile spasms and learning difficulty remained strong even when controlling for the number of tubers. PMID:15155396

  2. The response to ACTH is determined early in the treatment of infantile spasms.

    PubMed

    Mytinger, John R; Weber, Amanda; Heyer, Geoffrey L

    2015-03-01

    Although adrenocorticotropic hormone is the most commonly used treatment for infantile spasms in the United States, the optimal regimen for this indication is not known. The purpose of this study was to elucidate the optimal adrenocorticotropic hormone treatment duration. We conducted a retrospective chart review of response to adrenocorticotropic hormone among all patients with infantile spasms managed at our institution from January 2009 to September 2013. Treatment response was defined as clinical remission for greater than or equal to 28 days starting at any point within the adrenocorticotropic hormone course and remission of hypsarrhythmia (or definite EEG improvement if hypsarrhythmia was absent at baseline). For responders, the diagnostic and post-treatment EEG tracings were reviewed. Electroclinical remission was achieved in 21 of 39 patients (54%) receiving adrenocorticotropic hormone, including 11/25 (44%) receiving a long course (typically 12 weeks) and 10/14 (71%) receiving a short course (typically four weeks). The mean time to clinical remission was 5.8 days (median: 5 days; range: 1-20 days). Only one patient responded beyond two weeks of treatment. This study provides Class IV evidence that among patients with infantile spasms, the response to adrenocorticotropic hormone is most often determined early in the treatment course. Given the importance of rapid remission, clinicians should consider adding or changing treatment if infantile spasms do not resolve within two weeks of adrenocorticotropic hormone initiation. Further study is needed to determine the optimal adrenocorticotropic hormone regimen for infantile spasms. PMID:25644547

  3. The Controversial Role of Food Allergy in Infantile Colic: Evidence and Clinical Management

    PubMed Central

    Nocerino, Rita; Pezzella, Vincenza; Cosenza, Linda; Amoroso, Antonio; Di Scala, Carmen; Amato, Francesco; Iacono, Giuseppe; Berni Canani, Roberto

    2015-01-01

    Food allergies (FAs) are an increasing problem in Western countries, affecting up to 10% of young children. FAs are frequently associated with gastrointestinal manifestations. The role of FAs as a potential causative factor for infantile colic (IC) is still controversial. We report the most recent evidence on the pathogenesis, clinical and diagnostic aspects of FA-induced infantile colic (IC) and suggest a stepwise diagnostic approach. We selected articles on clinical and immunologic features, pathogenesis and management of FAs and IC from of 1981 to 2015. Original and review articles were identified through selective searches performed on PubMed, using the following terms: colic, infantile colic, food allergy and infantile colic, infantile colic treatment. The possible relationship between FAs and IC derives from the presence of dysmotility with visceral hypersensitivity and dysbiosis, demonstrated in both conditions, and the clinical response to dietary interventions. Unfortunately, the design of the studies, poor characterization of atopy and different dietary approaches limit the understanding of the importance of FAs in subjects with IC. The role of FAs in IC subjects without other symptoms of atopy remains controversial. However, where there is a suspicion of FAs, a short trial with an extensively hydrolyzed cow’s proteins formula or, if breast fed, with maternal elimination diet may be considered a reasonable option. PMID:25808260

  4. Ontogeny of memory: An update on 40 years of work on infantile amnesia.

    PubMed

    Madsen, Heather Bronwyn; Kim, Jee Hyun

    2016-02-01

    Given the profound influence that early life experiences can have upon psychosocial functioning later in life, it is intriguing that most adults fail to recall autobiographical events from their early childhood years. Infantile amnesia is the term used to describe this phenomenon of accelerated forgetting during infancy, and it is not unique to humans. Over the years, information garnered from animal studies has provided clues as to the neurobiological basis of infantile amnesia. The purpose of this review is to provide a neurobiological update on what we now know about infantile amnesia since the publication of Campbell and Spear's seminal review on the topic more than 40 years ago. We present evidence that infantile amnesia is unlikely to be explained by a unitary theory, with the protracted development of multiple brain regions and neurotransmitter systems important for learning and memory likely to be involved. The recent discovery that exposure to early life stress can alleviate infantile amnesia offers a potential explanation as to how early adversity can so profoundly affect mental health in adulthood, and understanding the neurobiological basis for this early transition may lead to the development of effective therapeutic interventions. PMID:26190765

  5. Neurodevelopmental outcomes in children with Down syndrome and infantile spasms

    PubMed Central

    Tapp, Sarah; Anderson, Tovi; Visootsak, Jeannie

    2015-01-01

    Down syndrome (DS) is the most common genetic cause of intellectual disability in the United States. The prevalence of seizure in individuals with DS is 1–13%, and infantile spasm (IS) occurs in 6–32% of those with seizures. Since IS is relatively common in children with DS, it is important to understand the impact IS has on the neurodevelopmental outcomes in order to provide appropriate anticipatory guidance to help maximize the potential of these children. Our study is the first to compare the neurodevelopmental outcomes of children with DS and IS (DS + IS) to children with DS and no history of seizures (DS ? IS). Using the Bayley Scales of Infant and Toddler Development III, we assessed the neurodevelopment of 29 subjects (eight DS + IS and 21 DS ? IS). Neurodevelopmental outcome was poor in the DS + IS cohort, but the delay in treatment does not appear to contribute to any differences in their developmental scores. However, when compared to children with DS ? IS, the DS + IS cohort scored approximately 20 points less in all domains including cognitive, motor, and language (P < 0.05). Our results indicate that IS may impact the neurodevelopmental outcomes of children with DS + IS; thus, it is important to provide ongoing developmental and educational assessments and potentially additional therapies for children with DS + IS. PMID:26523121

  6. Infantile hypertrophic pyloric stenosis--genetics and syndromes.

    PubMed

    Peeters, Babette; Benninga, Marc A; Hennekam, Raoul C M

    2012-11-01

    Infantile hypertrophic pyloric stenosis (IHPS) is a common condition in neonates that is characterized by an acquired narrowing of the pylorus. The aetiology of isolated IHPS is still largely unknown. Classic genetic studies have demonstrated an increased risk in families of affected infants. Several genetic studies in groups of individuals with isolated IHPS have identified chromosomal regions linked to the condition; however, these associations could usually not be confirmed in subsequent cohorts, suggesting considerable genetic heterogeneity. IHPS is associated with many clinical syndromes that have known causative mutations. Patients with syndromes associated with IHPS can be considered as having an extreme phenotype of IHPS and studying these patients will be instrumental in finding causes of isolated IHPS. Possible pathways in syndromic IHPS include: (neuro)muscular disorders; connective tissue disorders; metabolic disorders; intracellular signalling pathway disturbances; intercellular communication disturbances; ciliopathies; DNA-repair disturbances; transcription regulation disorders; MAPK-pathway disturbances; lymphatic abnormalities; and environmental factors. Future research should focus on linkage analysis and next-generation molecular techniques in well-defined families with multiple affected members. Studies will have an increased chance of success if detailed phenotyping is applied and if knowledge about the various possible causative pathways is used in evaluating results. PMID:22777173

  7. Incidence and treatment of infantile haemangioma in preterm infants.

    PubMed

    Goelz, Rangmar; Poets, Christian F

    2015-01-01

    Infantile haemangioma (IH) are vascular tumours with a unique growth dynamic, mostly absent at birth, growth in the first months followed by involution over several years, often resulting in residual skin changes. Immune-histologically, IH cells are exclusively glucose transporter protein-1 positive.The incidence of IH is increasing with decreasing gestational age, from 1-4% in term infants to 23% in those of <1000?g birth weight, with a female and Caucasian predominance. Discovery of systemic and topical beta blockers as an effective treatment option resulted in a rapid shift away from systemic steroids towards these drugs. For preterm infants, however, data on efficacy, pharmacokinetics and long-term safety are sparse or absent. Topical treatment without systemic side effects like cryotherapy may thus be an attractive alternative at an early growth stage (<10?mm). Indications for treatment with beta blockers, mostly propranolol systemically and timolol maleat 0.5% topically, are currently extrapolated from studies in older infants. Both seem effective, but adverse effects on sleep, circulation and metabolism are well described for propranolol. Long-term outcome data for either drug are missing. In conclusion, evidence on optimal IH treatment in preterms is lacking despite their high incidence; pharmacokinetic and clinical studies are warranted. PMID:25352093

  8. Molecular alterations of parotid saliva in infantile chronic recurrent parotitis.

    PubMed

    Morales-Bozo, Irene; Urzúa-Orellana, Blanca; Landaeta, Mirtha; Montalbán, Raúl; Torres, Jimena; Pinochet, Alvaro; Valverde, Gustavo; Muñoz-Martínez, Andrea

    2007-02-01

    Infantile chronic recurrent parotitis (ICRP) is an insidious disease whose etiopathogenesis remains an enigma. Alterations in the physical appearance of parotid saliva from ICRP patients have been frequently reported. However, sialochemical studies in regard to ICRP are very rare. The aim of this study was to determine whether saliva of ICRP patients presents major physicochemical and biochemical alterations compared with saliva from paired healthy controls. Parotid, whole, and submandibular/sublingual saliva was collected at an asymptomatic stage from 33 ICRP patients (5-16 y old, both sexes) and from 33 sex- and age-matched healthy controls. Saliva was analyzed for protein concentration, mode of protein diffusion on cellulose membranes, unidimensional sodium dodecylsulfate (SDS)-polyacrylamide gel electrophoresis protein profiles and zymographic profiles of metalloproteinase 2 (MMP-2) and metalloproteinase 9 (MMP-9). Parotid saliva of ICRP patients showed an increased protein concentration, altered mode of protein diffusion, a higher frequency of polypeptide bands of 43, 37, 33, 29, 26, 16, and 10 kD, higher asymmetry in the polypeptide profiles of both contralateral parotid saliva, and an increase in the frequency of MMP-2 and MMP-9. Parotid saliva of patients with ICRP is molecularly altered with respect to normal saliva. Some of the molecular differences could be related to the etiopathogenesis of the disease. PMID:17237723

  9. Association Between Coeliac Disease and Risk of Any Malignancy and Gastrointestinal Malignancy

    PubMed Central

    Han, Yuehua; Chen, Wuzhen; Li, Peiwei; Ye, Jun

    2015-01-01

    Abstract Coeliac disease (CD) is reported to be associated with risk of malignancy; however, this association remains unclear. We aimed to systematically evaluate the association between CD and risk of all malignancies as well as gastrointestinal (GI) malignancy specifically. The PUBMED and EMBASE databases were searched to identify eligible studies from 1960 to March 2015, without restriction. Two reviewers independently performed the study inclusion and data extraction methods. Odds ratios (ORs), risk ratios, or standardized incidence ratios were pooled using either a fixed- or a random-effects model. Sensitivity and subgroup analyses were used to explore sources of heterogeneity. A total of 17 studies were included in this meta-analysis. The pooled OR for risk of all malignancies was 1.25 (95% confidence interval [CI] 1.09–1.44), whereas the pooled OR for risk of GI malignancy was 1.60 (95% CI 1.39–1.84) and suggested an inverse association with CD. Moreover, patients with CD were at a higher risk of esophageal cancer (pooled OR?=?3.72, 95% CI 1.90–7.28) and small intestinal carcinoma (pooled OR?=?14.41, 95% CI 5.53–37.60), whereas no significant associations were observed for other GI cancers, including gastric, colorectal, liver, and pancreatic cancers. Subgroup analyses also indicated that the results were influenced by the CD diagnostic method, as well as the follow-up time after CD diagnosis. CD was associated with increased risk of all malignancies as well as GI malignancies, including esophageal cancer and small intestinal carcinoma. PMID:26402826

  10. Management of ascites due to gastrointestinal malignancy

    PubMed Central

    Saif, Muhammad W.; Siddiqui, Imran A. P.; Sohail, Muhammad A.

    2009-01-01

    Ascites is the pathological accumulation of fluid within the abdominal cavity. The most common cancers associated with ascites are adenocarcinomas of the ovary, breast, colon, stomach and pancreas. Symptoms include abdominal distension, nausea, vomiting, early satiety, dyspnea, lower extremity edema, weight gain and reduced mobility. There are many potential causes of ascites in cancer patients, including peritoneal carcinomatosis, malignant obstruction of draining lymphatics, portal vein thrombosis, elevated portal venous pressure from cirrhosis, congestive heart failure, constrictive pericarditis, nephrotic syndrome and peritoneal infections. Depending on the clinical presentation and expected survival, a diagnostic evaluation is usually indicated as it will impact both prognosis and the treatment approach. Key tests include serum albumin and protein and a simultaneous diagnostic paracentesis, checking ascitic fluid, WBCs, albumin, protein and cytology. Median survival after diagnosis of malignant ascites is in the range of 1 to 4 months; survival is apt to be longer for ovarian and breast cancers if systemic anti-cancer treatments are available. PMID:19700895

  11. Hodgkin's Disease and Other Malignant Lymphomas

    PubMed Central

    Rosenberg, Saul A.; Kaplan, Henry S.

    1970-01-01

    Systematic studies of the patterns of anatomic distribution, pathways of probable spread, and prognosis of the malignant lymphomas have been greatly aided by the development of new histopathologic classifications and the introduction of more sophisticated and precise diagnostic techniques, such as lymphangiography and laparotomy with splenectomy and retroperitoneal node biopsy. Concomitantly, megavoltage radiotherapy apparatus has made total-lymphoid radiotherapy feasible and practical, and the availability of a widening spectrum of chemotherapeutic agents has ushered in a new era of combination chemotherapy. Collectively, these diagnostic and therapeutic advances have already begun to yield a dramatic improvement in the prognosis of Hodgkin's disease and the other malignant lymphomas. ImagesFigure 1.Figure 2.Figure 3.Figure 4.Figure 5.Figure 6.Figure 7. PMID:4991356

  12. Magnetic resonance lymphography in gynaecological malignancies.

    PubMed

    Jahan, Noor; Narayanan, Priya; Rockall, Andrea

    2010-01-01

    Following the submission of this article to Cancer Imaging, unfortunately the European manufacturer of ferumoxtran-10 (Guerbet) has withdrawn the product pending further phase III studies. This is secondary to the view of the Committee for Medicinal Products for Human Use that the phase III data did not provide adequate statistical demonstration of the product's efficacy. Magnetic resonance lymphography holds much promise for the non-invasive evaluation of lymph nodes. The technique utilizes ultrasmall superparamagnetic particles of iron oxide and has been shown to be highly sensitive and specific in the diagnosis of malignant lymph nodes. This article reviews the technique and the performance of magnetic resonance lymphography in studies to date; alternative newer methods of nodal assessment such as fluorodeoxyglucose-positron emission tomography/computed tomography and diffusion-weighted magnetic resonance imaging are also discussed, with emphasis on gynaecological malignancies. PMID:20233680

  13. Stathmin 1 in normal and malignant hematopoiesis

    PubMed Central

    Machado-Neto, João Agostinho; Olalla Saad, Sara Teresinha; Traina, Fabiola

    2014-01-01

    Stathmin 1 is a microtubule destabilizer that plays an important role in cell cycle progression, segregation of chromosomes, clonogenicity, cell motility and survival. Stathmin 1 overexpression has been reported in malignant hematopoietic cells and Stathmin 1 inhibition reduces the highly proliferative potential of leukemia cell lines. However, during the differentiation of primary hematopoietic cells, Stathmin 1 expression decreases in parallel to decreases in the proliferative potential of early hematopoietic progenitors. The scope of the present review is to survey the current knowledge and highlight future perspectives for Stathmin 1 in normal and malignant hematopoiesis, with regard to the expression, function and clinical implications of this protein. [BMB Reports 2014; 47(12): 660-665] PMID:24667172

  14. External irradiation for malignant thyroid tumors

    SciTech Connect

    Chung, C.T.; Sagerman, R.H.; Ryoo, M.C.; King, G.A.; Yu, W.S.; Dalal, P.S.; Emmanuel, I.G.

    1980-09-01

    Thirty-eight patients with residual or recurrent primary thyroid cancers which did not take up I-131 were treated with external beam irradiation. Excluding 5 patients with malignant lymphoma, there were 23 patients with local disease and 10 with distant metastases. Doses ranged from 3500 to 7000 rads (35 to 70 Gy) among the 23 with local disease; local tumor control was achieved in 8. Six are alive and well 2 to 11 years later. External beam irradiation should be considered in locally advanced, incompletely resected, recurrent and metastatic thyroid malignancies of all histological types without I-131 uptake. Reviewed are the age and sex distribution, histology, stage, extent of surgery, and dose and radiotherapy technique as they affect survival and patterns of failure.

  15. Percutaneous catheter drainage for malignant pericardial effusion.

    PubMed

    Gatenby, R A; Hartz, W H; Kessler, H B

    1991-02-01

    Ultrasound (US)-guided and fluoroscopically guided pericardial catheter placement was performed in 12 patients with known underlying malignancy who had clinical and radiographic evidence of a significant pericardial effusion. US guidance facilitated placement of a 22-gauge needle by means of a subxyphoid or transthoracic approach. The tract was subsequently dilated over a wire under fluoroscopic guidance with placement of either an 8.5- or 10-F catheter. This technique successfully established pericardial drainage in all patients with excellent symptomatic relief. Cytologic findings were positive for malignancy in 10 of the 12 patients. Radiologically guided pericardiocentesis allowed safe, rapid stabilization of the condition of patients with symptoms from pericardial effusion. This resulted in excellent palliation in patients with terminal disease and improvement in the clinical status of other patients so that additional therapies, such as sclerosis with tetracycline or surgical placement of a pericardial window, could be performed on an elective basis. PMID:1799745

  16. Candida in potentially malignant oral disorders

    PubMed Central

    Sankari, S. Leena; Gayathri, K.; Balachander, N.; Malathi, L.

    2015-01-01

    Oro-pharyngeal cancer is a significant component in the global burden of cancer. A considerable proportion of oral squamous carcinomas develop from preexsiting potentially malignant disorder of the oral cavity. The term potentially malignant oral disorders (PMD) were proposed for the precancerous lesions and conditions by World Health Organization in 2007. PMD are considered an in-between clinical state, which showed increased risk for cancer development. Etiology of PMD is multifactorial. Tobacco and alcohol are the major risk factors. In recent years, role of candidal infection is recognized as a significant factor in the development of PMD. There is an enduring discussion whether Candida infection can be a cause of PMD or a superimposed infection in a preexisting lesion. This article highlights the association between Candida and PMD. PMID:26015698

  17. Ocular and orbital metastasis from systemic malignancies.

    PubMed

    Jain, I S; Dinesh, K; Mohan, K

    1987-01-01

    One hundred and seventy adult patients and one hundred and forty-eight children with systemic malignancies were examined for ocular and/or orbital metastases. Thirty-six patients (11.3%) had intraocular and/or orbital metastasis. Twenty-nine of the 36 patients (80.5%) had orbital metastasis, five patients (13.9%) had intraocular and two patients (5.5%) had intraocular and orbital metastasis. The commonest malignancy producing ocular metastasis was carcinoma breast in females and carcinoma bronchus in males. Eight of the 17 children had orbital deposits from leukaemia (47%) and six from neuroblastoma (35%). One child had uveal infiltration from acute lymphatic leukaemia. Ophthalmic metastasis were treated by external irradiation and/or combination chemotherapy whenever possible. The mean survival was five months for intraocular metastasis and 15.6 months for the orbital metastasis in adults. Prognosis was very poor in children. PMID:3508830

  18. Multidisciplinary management of malignant pleural effusion.

    PubMed

    Kaifi, Jussuf T; Toth, Jennifer W; Gusani, Niraj J; Kimchi, Eric T; Staveley-O'Carroll, Kevin F; Belani, Chandra P; Reed, Michael F

    2012-06-01

    Approximately 50% of patients with metastatic disease develop a malignant pleural effusion (MPE). Prompt clinical evaluation and treatment to achieve successful palliation are the main goals of management of MPE. Optimal treatment is still controversial and there is no universal standard approach. Management options include observation, thoracentesis, indwelling pleural catheter (IPC) or chest tube placement, pleurodesis, and surgical pleurectomy. The treatment for each patient should be based on symptoms, general condition, and life expectancy. PMID:21960207

  19. BCSC Grants: Etiology Of Early Breast Malignancy

    Cancer.gov

    The development of malignancy in the human breast is a poorly understood process. It is clear, however, that the occurrence of in situ cancers, particularly ductal carcinoma in situ (DCIS), is an important step in the evaluation of some invasive breast cancers. The investigators propose to elucidate the occurrence, biological features, and etiology of in situ and invasive breast cancers, with a particular focus on ductal carcinoma in situ (DCIS).

  20. Malignant melanoma showing smooth muscle differentiation.

    PubMed Central

    Banerjee, S S; Bishop, P W; Nicholson, C M; Eyden, B P

    1996-01-01

    A unique case of a metastatic non-desmoplastic sarcomatoid malignant melanoma in an axillary lymph node showing smooth muscle differentiation in a 54 year old woman is described. The tumour cells exhibited alpha-smooth muscle actin, HHF-35 and desmin positivity but were negative for S100 protein and HMB-45. Ultrastructural examination revealed smooth muscle phenotype and there was no evidence of myofibroblastic differentiation, a feature described previously in desmoplastic melanomas. Images PMID:8944620

  1. Functional MR Imaging in Chest Malignancies.

    PubMed

    Broncano, Jordi; Luna, Antonio; Sánchez-González, Javier; Alvarez-Kindelan, Antonio; Bhalla, Sanjeev

    2016-02-01

    With recent advances in MR imaging, its application in the thorax has been feasible. The performance of both morphologic and functional techniques in the evaluation of thoracic malignances has improved not only differentiation from benign etiologies but also treatment monitoring based on a multiparametric approach. Several MR imaging-derived parameters have been described as potential biomarkers linked with prognosis and survival. Therefore, an integral approach with a nonradiating and noninvasive technique could be an optimal alternative for evaluating those patients. PMID:26613879

  2. Targeting cell cycle regulators in hematologic malignancies.

    PubMed

    Aleem, Eiman; Arceci, Robert J

    2015-01-01

    Hematologic malignancies represent the fourth most frequently diagnosed cancer in economically developed countries. In hematologic malignancies normal hematopoiesis is interrupted by uncontrolled growth of a genetically altered stem or progenitor cell (HSPC) that maintains its ability of self-renewal. Cyclin-dependent kinases (CDKs) not only regulate the mammalian cell cycle, but also influence other vital cellular processes, such as stem cell renewal, differentiation, transcription, epigenetic regulation, apoptosis, and DNA repair. Chromosomal translocations, amplification, overexpression and altered CDK activities have been described in different types of human cancer, which have made them attractive targets for pharmacological inhibition. Mouse models deficient for one or more CDKs have significantly contributed to our current understanding of the physiological functions of CDKs, as well as their roles in human cancer. The present review focuses on selected cell cycle kinases with recent emerging key functions in hematopoiesis and in hematopoietic malignancies, such as CDK6 and its role in MLL-rearranged leukemia and acute lymphocytic leukemia, CDK1 and its regulator WEE-1 in acute myeloid leukemia (AML), and cyclin C/CDK8/CDK19 complexes in T-cell acute lymphocytic leukemia. The knowledge gained from gene knockout experiments in mice of these kinases is also summarized. An overview of compounds targeting these kinases, which are currently in clinical development in various solid tumors and hematopoietic malignances, is presented. These include the CDK4/CDK6 inhibitors (palbociclib, LEE011, LY2835219), pan-CDK inhibitors that target CDK1 (dinaciclib, flavopiridol, AT7519, TG02, P276-00, terampeprocol and RGB 286638) as well as the WEE-1 kinase inhibitor, MK-1775. The advantage of combination therapy of cell cycle inhibitors with conventional chemotherapeutic agents used in the treatment of AML, such as cytarabine, is discussed. PMID:25914884

  3. Targeting cell cycle regulators in hematologic malignancies

    PubMed Central

    Aleem, Eiman; Arceci, Robert J.

    2015-01-01

    Hematologic malignancies represent the fourth most frequently diagnosed cancer in economically developed countries. In hematologic malignancies normal hematopoiesis is interrupted by uncontrolled growth of a genetically altered stem or progenitor cell (HSPC) that maintains its ability of self-renewal. Cyclin-dependent kinases (CDKs) not only regulate the mammalian cell cycle, but also influence other vital cellular processes, such as stem cell renewal, differentiation, transcription, epigenetic regulation, apoptosis, and DNA repair. Chromosomal translocations, amplification, overexpression and altered CDK activities have been described in different types of human cancer, which have made them attractive targets for pharmacological inhibition. Mouse models deficient for one or more CDKs have significantly contributed to our current understanding of the physiological functions of CDKs, as well as their roles in human cancer. The present review focuses on selected cell cycle kinases with recent emerging key functions in hematopoiesis and in hematopoietic malignancies, such as CDK6 and its role in MLL-rearranged leukemia and acute lymphocytic leukemia, CDK1 and its regulator WEE-1 in acute myeloid leukemia (AML), and cyclin C/CDK8/CDK19 complexes in T-cell acute lymphocytic leukemia. The knowledge gained from gene knockout experiments in mice of these kinases is also summarized. An overview of compounds targeting these kinases, which are currently in clinical development in various solid tumors and hematopoietic malignances, is presented. These include the CDK4/CDK6 inhibitors (palbociclib, LEE011, LY2835219), pan-CDK inhibitors that target CDK1 (dinaciclib, flavopiridol, AT7519, TG02, P276-00, terampeprocol and RGB 286638) as well as the WEE-1 kinase inhibitor, MK-1775. The advantage of combination therapy of cell cycle inhibitors with conventional chemotherapeutic agents used in the treatment of AML, such as cytarabine, is discussed. PMID:25914884

  4. Diagnosis and treatment of malignant pleural mesothelioma.

    PubMed

    Rodríguez Panadero, Francisco

    2015-04-01

    There are three major challenges in the diagnosis of malignant pleural mesothelioma: mesothelioma must be distinguished from benign mesothelial hyperplasia; malignant mesothelioma (and its subtypes) must be distinguished from metastatic carcinoma; and invasion of structures adjacent to the pleura must be demonstrated. The basis for clarifying the first two aspects is determination of a panel of monoclonal antibodies with appropriate immunohistochemical evaluation performed by highly qualified experts. Clarification of the third aspect requires sufficiently abundant, deep biopsy material, for which thoracoscopy is the technique of choice. Video-assisted needle biopsy with real-time imaging can be of great assistance when there is diffuse nodal thickening and scant or absent effusion. Given the difficulties of reaching an early diagnosis, cure is not generally achieved with radical surgery (pleuropneumonectomy), so liberation of the tumor mass with pleurectomy/decortication combined with chemo- or radiation therapy (multimodal treatment) has been gaining followers in recent years. In cases in which surgery is not feasible, chemotherapy (a combination of pemetrexed and platinum-derived compounds, in most cases) with pleurodesis or a tunneled pleural drainage catheter, if control of pleural effusion is required, can be considered. Radiation therapy is reserved for treatment of pain associated with infiltration of the chest wall or any other neighboring structure. In any case, comprehensive support treatment for pain control in specialist units is essential: this acquires particular significance in this type of malignancy. PMID:25059587

  5. Targets for Ibrutinib Beyond B Cell Malignancies.

    PubMed

    Berglöf, A; Hamasy, A; Meinke, S; Palma, M; Krstic, A; Månsson, R; Kimby, E; Österborg, A; Smith, C I E

    2015-09-01

    Ibrutinib (Imbruvica™) is an irreversible, potent inhibitor of Bruton's tyrosine kinase (BTK). Over the last few years, ibrutinib has developed from a promising drug candidate to being approved by FDA for the treatment of three B cell malignancies, a truly remarkable feat. Few, if any medicines are monospecific and ibrutinib is no exception; already during ibrutinib's initial characterization, it was found that it could bind also to other kinases. In this review, we discuss the implications of such interactions, which go beyond the selective effect on BTK in B cell malignancies. In certain cases, the outcome of ibrutinib treatment likely results from the combined inhibition of BTK and other kinases, causing additive or synergistic, effects. Conversely, there are also examples when the clinical outcome seems unrelated to inhibition of BTK. Thus, more specifically, adverse effects such as enhanced bleeding or arrhythmias could potentially be explained by different interactions. We also predict that during long-term treatment bone homoeostasis might be affected due to the inhibition of osteoclasts. Moreover, the binding of ibrutinib to molecular targets other than BTK or effects on cells other than B cell-derived malignancies could be beneficial and result in new indications for clinical applications. PMID:26111359

  6. Cryosurgery for malignant tumours of the liver

    PubMed Central

    McKinnon, J. Gregory; Temple, Walley J.; Wiseman, David A.; Saliken, John C.

    1996-01-01

    Objective To evaluate the safety and efficacy of ultrasound-guided cryosurgery to treat malignant tumours of the liver. Design A prospective nonrandomized trial. The follow-up was complete and ranged from 8 to 35 months. Setting A university-affiliated hospital. Patients Ten patients with secondary malignant tumours of the liver; 1 with primary hepatoma. Interventions Computed portography for preoperative staging; laparotomy and ultrasonographic examination of the liver; cryosurgical ablation of liver tumours with or without a concomitant resection. Thirteen procedures were performed on 11 patients. Main Outcome Measures Preoperative morbidity, disease-free and overall survival. Results Of 24 lesions frozen, the procedure on 4 lesions was considered a technical failure because of persistent disease. There were no perioperative deaths. One patient had a liver abscess that resolved with percutaneous drainage. One patient had a biliary fistula that resolved spontaneously, and one had a transient rise in the serum creatinine level. Of 11 patients treated, 7 had a recurrence in the liver (persistent disease in 2 and new liver metastases in 5); 2 of these patients died. One patient died of distant disease with no local recurrence. At the time of writing, one patient was alive with extrahepatic disease and no local recurrence and two were free of disease. Conclusions Cryosurgery of the liver is a relatively safe procedure that allows treatment of otherwise un-resectable malignant disease. Proof of long-term benefit requires further experience and follow-up. PMID:8857990

  7. Malignant external otitis: early scintigraphic detection

    SciTech Connect

    Strashun, A.M.; Nejatheim, M.; Goldsmith, S.J.

    1984-02-01

    Pseudomonas otitis externa in elderly diabetics may extend aggressively to adjacent bone, cranial nerves, meninges, and vessels, leading to a clinical diagnosis of ''malignant'' external otitis. Early diagnosis is necessary for successful treatment. This study compares the findings of initial radiographs, thin-section tomography of temporal bone, CT scans of head and neck, technetium-99m methylene diphosphonate (MDP) and gallium-67 citrate scintigraphy, and single-photon emission computed tomography (SPECT) for detection of temporal bone osteomylitis in ten patients fulfilling the clinical diagnostic criteria of malignant external otitis. Skull radiographs were negative in all of the eight patients studied. Thin-section tomography was positive in one of the seven patients studied using this modality. CT scanning suggested osteomyelitis in three of nine patients. Both Tc-99m and Ga-67 citrate scintigraphy were positive in 10 of 10 patients. These results suggest that technetium and gallium scintigraphy are more sensitive than radiographs and CT scans for early detection of malignant external otitis.

  8. Fertility issues in patients with hematologic malignancies.

    PubMed

    Loren, Alison W

    2015-12-01

    An essential component of a cancer patient's comprehensive care is addressing potential threats to his or her reproductive health. Providers should discuss the risk of infertility with newly diagnosed patients and offer the chance to consult with a reproductive specialist as early as possible. Standard fertility preservation options include embryo or oocyte cryopreservation for women and sperm banking for men; all options for pre-pubertal children are experimental. Patients with hematologic malignancies are a distinct population in whom standard options may present special challenges, and alternative management strategies are being explored. Unique approaches in hematologic malignancy patients include experimental techniques, such as hormonal therapy, referrals to reproductive specialists after cancer treatment, or discontinuation of tyrosine kinase inhibitor therapy in appropriate chronic myelogenous leukemia patients. Importantly, expedited communication between hematologists and reproductive specialists may greatly enhance the quality of care for these patients. Facilitation of referrals will both improve the quality-of-life and expand the prospect of parenthood in survivors. There are ample opportunities to advance the field of oncofertility through additional research, especially in hematologic malignancy patients. PMID:26637713

  9. Infantile spasms and early immunization against whooping cough. Danish survey from 1970 to 1975.

    PubMed Central

    Melchior, J C

    1977-01-01

    113 cases of infantile spasms were diagnosed in the period 1 April 1970 to 31 March 1975 after Denmark changed her immunization programme. Previously whooping cough vaccine was given as the triple combination at 5, 6, and 15 months of age. From 1 April 1970 it was given as a monovalent vaccine at 5 and 9 weeks of age and at 10 months of age. A comparison with previous material of 86 cases of infantile spasms from 1957 to 1967 showed no change in the age at onset. Though there may be an occasional connection between immunization and infantile spasms, the most important factor is a time-coincidence between any immunization given at a certain age with the neurological disorders which are natural for that age. PMID:836065

  10. A Pulse Rapamycin Therapy for Infantile Spasms and Associated Cognitive Decline

    PubMed Central

    Raffo, Emmanuel; Coppola, Antonietta; Ono, Tomonori; Briggs, Stephen W.; Galanopoulou, Aristea S.

    2011-01-01

    Infantile spasms are seizures manifesting within a spectrum of epileptic encephalopathies of infancy that often lead to cognitive impairment. Their current therapies, including adrenocorticotropic hormone (ACTH), high dose steroids, or vigabatrin, are not always effective and may be associated with serious side effects. Overactivation of the TORC1 complex of the mTOR pathway is implicated in the pathogenesis of certain genetic and acquired disorders that are linked with infantile spasms, like tuberous sclerosis. Here, we tested the therapeutic potential of rapamycin, a TORC1 inhibitor, as a potential treatment for infantile spasms in the multiple-hit rat model of ACTH-refractory symptomatic infantile spasms, which is not linked to tuberous sclerosis. Rapamycin or vehicle were given after spasms appeared. Their effects on spasms, other seizures, performance in Barnes maze, and expression of the phosphorylated S6 ribosomal protein (pS6: a TORC1 target) in the cortex, using immunofluorescence, were compared. Rapamycin suppressed spasms dose-dependently and improved visuospatial learning, although it did not reduce the frequency of other emerging seizures. High-dose pulse rapamycin effected acute and sustained suppression of spasms and improved cognitive outcome, without significant side effects. Therapeutically effective rapamycin doses normalized the pS6 expression, which was increased in perilesional cortical regions of pups with spasms. These findings support that pathological overactivation of TORC1 may be implicated in the pathogenesis of infantile spasms, including those that are not linked to tuberous sclerosis. Furthermore, a high-dose, pulse rapamycin treatment is a promising, well tolerated and disease-modifying new therapy for infantile spasms, including those refractory to ACTH. PMID:21504792

  11. Pathophysiology of Massive Infantile Spasms: Perspective on the Putative Role of the Brain Adrenal Axis

    PubMed Central

    Baram, Tallie Z.

    2013-01-01

    Massive infantile spasms are an age-specific seizure syndrome of infancy. Uniquely, the spasms respond to hormonal manipulation using adrenocorticotropic hormone (ACTH) or glucocorticoids. A hypothesis explaining the efficacy of hormonal therapy, age-specificity, multiple causative factors, and spontaneous resolution of infantile spasms is presented. Corticotropin-releasing hormone (CRH), an excitant neuropeptide suppressed by ACTH/steroids, is implicated. Evidence for the age-specific convulsant properties of CRH is presented, and a putative scenario in which a stressinduced enhancement of endogenous CRH-mediated seizures is discussed. Clinical testing of the CRH-excess theory and its therapeutic implications are suggested. PMID:8388675

  12. Vigabatrin-induced MRI changes associated with extrapyramidal symptoms in a child with infantile spasms.

    PubMed

    Schonstedt, Valeria; Stecher, Ximena; Venegas, Viviana; Silva, Claudio

    2015-10-01

    Vigabatrin is an antiepileptic drug used for treatment of infantile spasms. We present a female patient with infantile spasms in treatment with vigabatrin who developed ataxic movements. MRI demonstrated a symmetrical pattern of thalamic and globi pallidi diffusion restriction. While these image features have been widely described to be related to the use of vigabatrin, this case highlights the development of movement disorders in association with MRI signal changes. Awareness of the reversible nature of this condition is reassuring for the treating team and avoids unjustified studies. PMID:26306928

  13. The psoas muscle as cause of low back pain in infantile cerebral palsy

    PubMed Central

    Camoriano, R.; Valle, M.; Boero, S.

    2008-01-01

    Psoas muscle spasticity is hypothesised as a rare cause of low back pain in patients with infantile cerebral palsy. The authors describe a new manoeuvre for the study of psoas tenderness and ultrasound (US)-guided transabdominal botulinum toxin injection technique. A possible causal relationship between psoas tension and low back pain was found incidentally in two examined cases. In subsequent patients, botulinum toxin was injected and, in cases of disappearance of symptoms, the psoas tendon was sectioned at the pelvic brim with definitive disappearance of pain. The relationship between psoas tension and low back pain in patients with infantile cerebral palsy seems likely, given the result in the four patients. PMID:19384481

  14. Screening of Inherited Metabolic Disorders in Infants with Infantile Spasms.

    PubMed

    Liu, Xiao-Ming; Li, Rui; Chen, Sheng-Zhi; Sang, Yan; Chen, Jiao; Fan, Cong-Hai

    2014-11-23

    The objective of this study is to explore the incidence of inherited metabolic disorders (IMD) in infants with infantile spasms (IS), with an attempt to improve the early diagnosis and etiological and symptomatic treatment. Urine and blood samples were collected from 60 IS patients and analyzed for the quantification of amino acids, organic acids, and fatty acids by gas chromatography-mass spectrometry and tandem mass spectrum. Routine urine tests, hepatic function tests, blood biochemistry, brain imaging, as well as examinations of the brain stem auditory/visual evoked potentials were also examined. In addition to antiepileptic therapy, etiological and symptomatic treatments were also conducted in infants with confirmed IMD and the follow-up lasted for 6 months in these pediatric patients. Metabolic disorders were found in 28 (46.67 %) of 60 IS infants, among them 13 (21.67 %) were confirmed to be with IMD. Twelve of these 13 IS patients with definite IMD diagnoses (92.31 %) experienced varying degrees of delayed development of intelligence and motor function, 8 patients (61.54 %) had abnormal cranial CT or MRI findings, 11 patients (84.61 %) had abnormal brain stem evoked potentials, 4 patients (30.77 %) had abnormal hepatic functions, 3 patients (23.07 %) had abnormal blood biochemistry, 2 patients (15.38 %) had positive (+ to ++) results for routine urine ketones, and 2 patients (15.38 %) had skin lesions. After treatment in children who were diagnosed IMD, the well controlled epileptic seizures and the satisfactory developments in mental and motor were found in 4 cases of methylmalonic acidemia, 2 cases of classical phenylketonuria, and one case of biotin deficiency disease, glutaric acidemia type I, and 4-hydroxybutyric aciduria in each. IMD is a key biological cause in IS. Early screening for IMD is warranted in IS infants to facilitate the improvement for the prognosis and an early etiological treatment. PMID:25417060

  15. Vigabatrin retinal toxicity in children with infantile spasms

    PubMed Central

    Wright, Tom; Cortese, Filomeno; Kumarappah, Ananthavalli; Snead, O. Carter; Buncic, Joseph R.

    2014-01-01

    Objectives: To determine time to vigabatrin (VGB, Sabril; Lundbeck, Deerfield, IL) induced retinal damage in children with infantile spasms (IS) and to identify risk factors for VGB-induced retinal damage (VGB-RD). Methods: Observational cohort study including 146 participants (68 female, 81 male) with IS, an age-specific epilepsy syndrome of early infancy, treated with VGB. Participants ranged from 3 to 34.9 months of age (median 7.6 months). The median duration of VGB treatment was 16 months (range 4.6–78.5 months). Electroretinograms (ERGs) were performed according to the Standards of the International Society for Clinical Electrophysiology of Vision. Inclusion required baseline (pre-VGB or within 4 weeks of starting VGB treatment) and at least 2 follow-up ERGs. Significant reduction from baseline of the 30-Hz ERG flicker amplitude on 2 consecutive visits identified VGB-RD. Kaplan-Meier survival analyses depicted the effect of duration of VGB on VGB-RD. Results: These data represent the largest survival analysis of children treated with VGB who did not succumb to retinal toxicity during the study. Thirty of the 146 participants (21%) showed VGB-RD. The ERG amplitude reduced with duration of VGB treatment (p = 0.0004) with no recovery after VGB cessation. With 6 and 12 months of VGB treatment, 5.3% and 13.3%, respectively, developed VGB-RD. There was neither effect of age of initiation of VGB treatment nor sex of the child on survival statistics and no significant effect of cumulative dosage on the occurrence of VGB-RD. Conclusions: Minimizing VGB treatment to 6 months will reduce the prevalence of VGB-RD in patients with IS. PMID:25381295

  16. Contrast Sensitivity Is Reduced in Children with Infantile Spasms

    PubMed Central

    Mirabella, Giuseppe; Morong, Sharon; Buncic, J. Raymond; Snead, O. Carter; Logan, William J.; Weiss, Shelly K.; Abdolell, Mohamed; Westall, Carol A.

    2013-01-01

    Purpose To investigate whether visual deficits in children with infantile spasm (IS) are the result of seizure activity or of treatment with the anticonvulsant drug vigabatrin (VGB). Methods Vision function was determined in three experiments by determining peak contrast sensitivity (CS) and grating acuity (GA) with the sweep visual evoked potential. Cross-sectional study A: 34 children, including 11 patients with childhood epilepsy with exposure to VGB for at least 6 months, 10 with childhood epilepsy exposed to antiepileptic drugs other than VGB, and 13 normally developing children. Cross-sectional study B: 32 children, including 16 with IS naïve to VGB and 16 normally developing children. Longitudinal study: seven children with IS naïve to VGB, with subsequent follow-up 5 to 10 months after starting VGB. Results In cross-sectional study A, the median CS was reduced by 0.5 log units (P = 0.025) in children with epilepsy exposed to VGB compared with those exposed to other antiepileptic drugs and normally developing children. In cross-sectional study B, the median CS was reduced by 0.25 log units (P = 0.0015) in children with IS (VGB naïve) compared with normally developing children. Longitudinal assessment showed no decrease in CS in children with IS who were followed up 5 to 10 months after starting VGB. There was no difference in GA among groups in any of the experiments. Conclusions Patients with IS have CS deficits, but a sparing of GA. This deficit is present before VGB treatment and does not worsen with treatment onset. Results suggest that visual dysfunction is largely the result of the seizures themselves. PMID:17652730

  17. Cause-Specific Mortality Due to Malignant and Non-Malignant Disease in Korean Foundry Workers

    PubMed Central

    Yoon, Jin-Ha; Ahn, Yeon-Soon

    2014-01-01

    Background Foundry work is associated with serious occupational hazards. Although several studies have investigated the health risks associated with foundry work, the results of these studies have been inconsistent with the exception of an increased lung cancer risk. The current study evaluated the mortality of Korean foundry workers due to malignant and non-malignant diseases. Methods This study is part of an ongoing investigation of Korean foundry workers. To date, we have observed more than 150,000 person-years in male foundry production workers. In the current study, we stratified mortality ratios by the following job categories: melting-pouring, molding-coremaking, fettling, and uncategorized production work. We calculated standard mortality ratios (SMR) of foundry workers compare to general Korean men and relative risk (RR) of mortality of foundry production workers reference to non-production worker, respectively. Results Korean foundry production workers had a significantly higher risk of mortality due to malignant disease, including stomach (RR: 3.96; 95% CI: 1.41–11.06) and lung cancer (RR: 2.08; 95% CI: 1.01–4.30), compared with non-production workers. High mortality ratios were also observed for non-malignant diseases, including diseases of the circulatory (RR: 1.92; 95% CI: 1.18–3.14), respiratory (RR: 1.71; 95% CI: 1.52–21.42 for uncategorized production worker), and digestive (RR: 2.27; 95% CI: 1.22–4.24) systems, as well as for injuries (RR: 2.36; 95% CI: 1.52–3.66) including suicide (RR: 3.64; 95% CI: 1.32–10.01). Conclusion This study suggests that foundry production work significantly increases the risk of mortality due to some kinds of malignant and non-malignant diseases compared with non-production work. PMID:24505454

  18. Mediastinal Mature Teratoma With Malignant Carcinomatous Transformation (Somatic-Type Malignancy) With Metastatic Course.

    PubMed

    Habougit, Cyril; Yvorel, Violaine; Sulaiman, Abdulrazzaq; Hag, Bachir; Péoc'h, Michel; Forest, Fabien

    2015-12-01

    We report the case of a 76-year-old patient presenting with an anterior mediastinal heterogeneous mass. Surgical biopsy revealed a solid and cystic lesion filled with hair. Pathological examination showed an atypical papillary epithelial lining without other germ cell tumor or immature teratoma associated. The final diagnosis was a mature teratoma of the mediastinum with somatic-type malignancy (carcinomatous transformation). After 8-month follow-up, subcutaneous and lymph node metastatic lesions of the carcinomatous component were identified. Subtyping of the malignant component within germ cell tumors is an important challenge for therapeutic options and prognosis. PMID:26113666

  19. A Common Polymorphism within the IGF2 Imprinting Control Region Is Associated with Parent of Origin Specific Effects in Infantile Hemangiomas

    PubMed Central

    Schultz, Brent; Yao, Xiaopan; Deng, Yanhong; Waner, Milton; Spock, Christopher; Tom, Laura; Persing, John; Narayan, Deepak

    2015-01-01

    Infantile hemangioma (IH) is the most common tumor of the pediatric age group, affecting up to 4% of newborns ranging from inconsequential blemishes, to highly aggressive tumors. Following well defined growth phases (proliferative, plateau involutional) IH usually regress into a fibro-fatty residuum. Despite the high prevalence of IH, little is known regarding the pathogenesis of disease. A reported six fold decrease in IGF2 expression (correlating with transformation of proliferative to involuted lesions) prompted us to study the IGF-2 axis further. We demonstrate that IGF2 expression in IH is strongly related to the expression of a cancer testes and suspected oncogene BORIS (paralog of CTCF), placing IH in the unique category of being the first known benign BORIS positive tumor. IGF2 expression was strongly and positively related to BORIS transcript expression. Furthermore, a stronger association was made when comparing BORIS levels against the expression of CTCF via either a percentage or difference between the two. A common C/T polymorphism at CTCF BS6 appeared to modify the correlation between CTCF/BORIS and IGF2 expression in a parent of origin specific manner. Moreover, these effects may have phenotypic consequences as tumor growth also correlates with the genotype at CTCF BS6. This may provide a framework for explaining the clinical variability seen in IH and suggests new insights regarding CTCF and BORIS related functionality in both normal and malignant states. PMID:26496499

  20. A Common Polymorphism within the IGF2 Imprinting Control Region Is Associated with Parent of Origin Specific Effects in Infantile Hemangiomas.

    PubMed

    Schultz, Brent; Yao, Xiaopan; Deng, Yanhong; Waner, Milton; Spock, Christopher; Tom, Laura; Persing, John; Narayan, Deepak

    2015-01-01

    Infantile hemangioma (IH) is the most common tumor of the pediatric age group, affecting up to 4% of newborns ranging from inconsequential blemishes, to highly aggressive tumors. Following well defined growth phases (proliferative, plateau involutional) IH usually regress into a fibro-fatty residuum. Despite the high prevalence of IH, little is known regarding the pathogenesis of disease. A reported six fold decrease in IGF2 expression (correlating with transformation of proliferative to involuted lesions) prompted us to study the IGF-2 axis further. We demonstrate that IGF2 expression in IH is strongly related to the expression of a cancer testes and suspected oncogene BORIS (paralog of CTCF), placing IH in the unique category of being the first known benign BORIS positive tumor. IGF2 expression was strongly and positively related to BORIS transcript expression. Furthermore, a stronger association was made when comparing BORIS levels against the expression of CTCF via either a percentage or difference between the two. A common C/T polymorphism at CTCF BS6 appeared to modify the correlation between CTCF/BORIS and IGF2 expression in a parent of origin specific manner. Moreover, these effects may have phenotypic consequences as tumor growth also correlates with the genotype at CTCF BS6. This may provide a framework for explaining the clinical variability seen in IH and suggests new insights regarding CTCF and BORIS related functionality in both normal and malignant states. PMID:26496499

  1. The role of epigenetics in kidney malignancies

    PubMed Central

    la Rosa, Alfredo Harb-De; Acker, Matthew; Swain, Sanjaya

    2015-01-01

    Introduction Renal cell carcinomas (RCC) are collectively the third most common type of genitourinary neoplasms, surpassed only by prostate and bladder cancer. Cure rates for renal cell carcinoma are related to tumor grade and stage; therefore, diagnostic methods for early detection and new therapeutic modalities are of paramount importance. Epigenetics can be defined as inherited modifications in gene expression that are not encoded in the DNA sequence itself. Epigenetics may play an important role in the pursuit of early diagnosis, accurate prognostication and identification of new therapeutic targets. Material and methods We used PubMed to conduct a comprehensive search of the English medical literature using search terms including epigenetics, DNA methylation, histone modification, microRNA regulation (miRNA) and RCC. In this review, we discuss the potential application of epigenetics in the diagnosis, prognosis and treatment of kidney cancer. Results During the last decade, many different types of epigenetic alterations of DNA have been found to be associated with malignant renal tumors. This has led to the research of the diagnostic and prognostic implications of these changes in renal malignancies as well as to the development of novel drugs to target these changes, with the aim of achieving a survival benefit. Conclusions Epigenetics has become a promising field in cancer research. The potential to achieve early detection and accurate prognostication in kidney cancer might be feasible through the application of epigenetics. The possibility to reverse these epigenetic changes with new therapeutic agents motivates researchers to continue pursuing better treatment options for kidney cancer and other malignancies. PMID:26251734

  2. Surgery in (pre)malignant celiac disease

    PubMed Central

    van de Water, Jolanda MW; Nijeboer, Petula; de Baaij, Laura R; Zegers, Jessy; Bouma, Gerd; Visser, Otto J; van der Peet, Donald L; Mulder, Chris JJ; Meijerink, Wilhelmus JHJ

    2015-01-01

    AIM: To report the outcome of surgery in patients with (pre)malignant conditions of celiac disease (CD) and the impact on survival. METHODS: A total of 40 patients with (pre)malignant conditions of CD, ulcerative jejunitis (n = 5) and enteropathy associated T-cell lymphoma (EATL) (n = 35), who underwent surgery between 2002 and 2013 were retrospectively evaluated. Data on indications, operative procedure, post-operative morbidity and mortality, adjuvant therapy and overall survival (OS) were collected. Eleven patients with EATL who underwent chemotherapy without resection were included as a control group for survival analysis. Patients were followed-up every three months during the first year and at 6-mo intervals thereafter. RESULTS: Mean age at resection was 62 years. The majority of patients (63%) underwent elective laparotomy. Functional stenosis (n = 13) and perforation (n = 12) were the major indications for surgery. In 70% of patients radical resection was performed. Early postoperative complications, mainly due to leakage or sepsis, occurred in 14/40 (35%) of patients. Eight patients required reoperation. More patients who underwent resection in the acute setting (n = 3, 20%) died compared to patients treated in the elective setting. With a median follow-up of 20 mo, seven patients (18%) required reoperation due to long-term complications. Significantly more patients who underwent acute surgery could not be treated with adjuvant chemotherapy. Patients who first underwent surgical resection showed significantly better OS than patients who received chemotherapy without resection. CONCLUSION: Although the complication rate is high, the preferred first step of treatment in (pre)malignant CD consists of local resection as early as possible to improve survival. PMID:26604647

  3. Incidence of Subsequent Cholangiocarcinomas After Another Malignancy

    PubMed Central

    Mao, Kai; Jiang, Wen; Liu, Jieqiong; Wang, Jie

    2015-01-01

    Abstract Cholangiocarcinoma (CCA) characterized by late diagnosis and poor outcomes represents the commonest malignancy of biliary tract. Understanding metachronous cancer associations may achieve earlier detection. We aimed to evaluate the risk of subsequent CCAs among common cancer survivors. The National Cancer Institute's Surveillance, Epidemiology, and End Results database (1973–2010) was reviewed for patients with 1 of the 25 primary cancers. Standardized incidence ratios (SIRs) were calculated as an approximation of relative risk for subsequent CCAs after primary malignancy. Data were stratified by age at primary cancer diagnosis, latency period, and application of radiation. A total of 1487 patients developed subsequent CCAs. For patients diagnosed with primary cancers between the ages 20 and 39 years, the risk was increased among colon (SIR 14.65), gallbladder (129.29), and uterus (7.29) cancer survivors. At ages of 40 to 59 years, oral cavity and pharynx (1.89), stomach (3.24), colon (1.76), gallbladder (11.78), and lung cancers (1.75) were associated with increased risk. We found persistently elevated SIRs after colon and gallbladder cancer between ages 60 and 79 years. The SIR remained significant among gallbladder cancer survivors diagnosed after 80 years. Gallbladder cancer showed elevated risk at all of the latency periods except first 6 to 11 months. Increased risk of lung cancer (1.66) was detected after 120 months. However, radiation therapy did not contribute to increased risk. This population-based study suggests that several initial cancers are associated with elevated risk of CCA. The increased risk may be due to shared genetic or environmental etiological factors between these malignancies. Lower threshold for CCA surveillance may be warranted in high-risk patients. PMID:25715268

  4. Multiparametric MR Imaging in Abdominal Malignancies.

    PubMed

    Luna, Antonio; Pahwa, Shivani; Bonini, Claudio; Alcalá-Mata, Lidia; Wright, Katherine L; Gulani, Vikas

    2016-02-01

    Modern MR imaging protocols can yield both anatomic and functional information for the assessment of hepatobiliary and pancreatic malignancies. Diffusion-weighted imaging is fully integrated into state-of-the-art protocols for tumor detection, characterization, and therapy monitoring. Hepatobiliary contrast agents have gained ground in the evaluation of focal liver lesions during the last years. Perfusion MR imaging is expected to have a central role for monitoring therapy in body tumors treated with antivascular drugs. Approaches such as Magnetic resonance (MR) elastography and (1)H-MR spectroscopy are still confined to research centers, but with the potential to grow in a short time frame. PMID:26613880

  5. Molecular targeting in childhood malignancies using nanoparticles

    NASA Astrophysics Data System (ADS)

    Satake, Noriko; Barisone, Gustavo; Diaz, Elva; Nitin, Nitin; Nolta, Jan; Lam, Kit

    2012-06-01

    The goal of our project is to develop a new therapy for childhood malignancies using nanoformulated siRNA targeting Mxd3, a molecule in the Sonic Hedgehog signaling pathway, which we believe is important for cell survival. We plan to use cancer-specific ligands and superparamagnetic iron oxide nanoparticles (SPIO NPs) to carry siRNA. This delivery system will be tested in mouse xenograft models that we developed with primary cancer tissues. Our current focus is acute lymphoblastic leukemia (ALL), the most common cancer in children. We report our progress to date.

  6. [Zygomycosis (mucormycosis) in patients with haematologic malignancy].

    PubMed

    Jensen, Eva Magrethe Precht; Clemmensen, Stine; Bjørndal, Kristine; Krogdahl, Annelise

    2011-01-31

    Zygomycosis is an invasive and increasingly emerging life-threatening infection. Diabetes is the most common risk factor; however, zygomycosis has increased among patients with haematologic malignancy, which is now the second most common risk factor with an incidence of 16%. Rapid diagnosis and treatment are essential for patient survival. In the Danish literature, only a few cases have been reported. We present two cases of zygomycosis, both with a fatal outcome, and we discuss the pathogenesis and treatment of invasive zygomycosis. PMID:21276400

  7. Tyrosine kinase gene rearrangements in epithelial malignancies

    PubMed Central

    Shaw, Alice T.; Hsu, Peggy P.; Awad, Mark M.; Engelman, Jeffrey A.

    2014-01-01

    Chromosomal rearrangements that lead to oncogenic kinase activation are observed in many epithelial cancers. These cancers express activated fusion kinases that drive the initiation and progression of malignancy, and often have a considerable response to small-molecule kinase inhibitors, which validates these fusion kinases as ‘druggable’ targets. In this Review, we examine the aetiologic, pathogenic and clinical features that are associated with cancers harbouring oncogenic fusion kinases, including anaplastic lymphoma kinase (ALK), ROS1 and RET. We discuss the clinical outcomes with targeted therapies and explore strategies to discover additional kinases that are activated by chromosomal rearrangements in solid tumours. PMID:24132104

  8. An Unusual Case of Desmoplastic Malignant Melanoma

    PubMed Central

    Javabal, Pandiaraja; Subramanian, Viswanathan

    2015-01-01

    Desmoplastic malignant melanoma is a rare variant of spindle cell melanoma, commonly seen in older adults, on sun-exposed areas. It accounts for 1-4% of all cases of cutaneous melanoma. The common location of the desmoplastic melanoma is the head and neck region, whereas, other sites are less common. Regional lymph node involvement is reported in 0 to 13.7% of the cases, which is less frequent than other cutaneous melanomas. A 75-year-old male presented with an ulceroproliferative growth on the left foot that was diagnosed as desmoplastic melanoma with regional lymph node metastasis and in transit metastasis, with extensive pulmonary metastasis. PMID:25949027

  9. Water content and structure in malignant and benign skin tumours

    NASA Astrophysics Data System (ADS)

    Gniadecka, M.; Nielsen, O. F.; Wulf, H. C.

    2003-12-01

    Analysis of the low frequency region of Raman spectra enables determination of water structure. It has been previously demonstrated by various techniques that water content and possibly also the water structure is altered in some malignant tumours. To further elucidate possible change in water structure in tumours we performed NIR FT Raman spectroscopy on biopsies from selected benign and malignant skin tumours (benign: seborrheic keratosis, pigmented nevi; malignant: malignant melanoma, basal cell carcinoma). We did not observe any differences in water content between malignant and benign skin tumours with an exception of seborrheic keratosis, in which the water content was decreased. Increase in the tetrahedral (free) water was found in malignant skin tumours and sun-damaged skin relative to normal young skin and benign skin tumours. This finding may add to the understanding of molecular alterations in cancer.

  10. Intracranial malignant melanoma: A report of 7 cases

    PubMed Central

    MA, YUNFENG; GUI, QIUPING; LANG, SENYANG

    2015-01-01

    The aim of the present study was to investigate the clinical diagnosis and treatment of intracranial malignant melanoma. For this purpose, the clinical manifestation, signs, cerebrospinal fluid (CSF) contents, imageology, pathological features, treatment and prognosis of 7 cases of intracranial malignant melanoma were analyzed in The Chinese PLA General Hospital (Beijing, China) from 1996 to 2013. All the melanoma cases were confirmed by histopathology, and CSF cytopathology demonstrated that there were 5 cases of primary malignant melanoma and 2 cases of secondary malignant melanoma. Among the patients, 4 presented with >1 pigmented nevus in the skin, and 1 presented with skin melanoma. Intracranial malignant melanoma mostly affects middle-aged males. CSF cytopathology and imageology (particularly enhanced magnetic resonance), are important tools in the diagnosis of the disease. Particularly, when a patient presents with a pigmented nevus in the skin and an abnormal lesion in the brain, a diagnosis of intracranial malignant melanoma should be considered.

  11. Optimizing Care With a Standardized Management Protocol for Patients With Infantile Spasms.

    PubMed

    Fedak, Erin M; Patel, Anup D; Heyer, Geoffrey L; Wood, Eric G; Mytinger, John R

    2015-09-01

    The primary aim of this quality improvement initiative was to increase the number of patients receiving first-line therapy (adrenocorticotropic hormone, corticosteroids, vigabatrin) as the initial treatment for infantile spasms. We implemented a standardized management protocol for infantile spasms based on the best available data and expert consensus. To assess the impact of this intervention, we compared the 3-month remission rates between prestandardization (January 2009 to August 2012) and poststandardization (September 2012 to May 2014) cohorts. We found that the percentage of patients receiving first-line therapy as the initial treatment was 57% (31/54) in the prestandardization cohort and 100% (35/35) in the poststandardization cohort (P < .001). The rate of infantile spasms remission was higher poststandardization compared to prestandardization (78.8% vs 30.6%, P < .001). Management standardization led to all patients receiving first-line therapy as the initial treatment and was associated with a significantly improved rate of infantile spasms remission 3 months after diagnosis. PMID:25535057

  12. Massive expansion of SCA2 with autonomic dysfunction, retinitis pigmentosa, and infantile spasms

    PubMed Central

    Shafrir, Y.; Hrivnak, J.; Patterson, M.C.; Tennison, M.B.; Clark, H.B.; Gomez, C.M.

    2011-01-01

    Objective: To provide clinical data on a cohort of 6 patients with massive expansion (>200 CAG repeats) of spinocerebellar ataxia type 2 (SCA2) and investigate possible pathways of pathogenesis using bioinformatics analysis of ATXN2 networks. Methods: We present data on 6 patients with massive expansion of SCA2 who presented in infancy with variable combinations of hypotonia, global developmental delay, infantile spasms, and retinitis pigmentosa. ATXN2 is known to interact with a network of synaptic proteins. To investigate pathways of pathogenesis, we performed bioinformatics analysis on ATXN2 combined with known genes associated with infantile spasms, retinitis pigmentosa, and synaptic function. Results: All patients had a progressive encephalopathy with autonomic dysfunction, 4 had retinitis pigmentosa, and 3 had infantile spasms. The bioinformatics analysis led to several interesting findings. First, an interaction between ATXN2 and SYNJ1 may account for the development of retinitis pigmentosa. Second, dysfunction of postsynaptic vesicle endocytosis may be important in children with this progressive encephalopathy. Infantile spasms may be associated with interactions between ATXN2 and the postsynaptic structural proteins MAGI2 and SPTAN1. Conclusions: Severe phenotype in children with massive expansion of SCA2 may be due to a functional deficit in protein networks in the postsynapse, specifically involving vesicle endocytosis. PMID:21880993

  13. Positron emission tomography findings in children with infantile spasms and autism.

    PubMed

    Dilber, Cengiz; Cal??kan, Mine; Sönmezo?lu, Kerim; Ni?li, Serap; Mukaddes, Nahit Motavalli; Tatl?, Burak; Ayd?nl?, Nur; Ekici, Bar??; Özmen, Meral

    2013-03-01

    The purpose of this study was to evaluate positron emission tomography (PET) findings in patients diagnosed with infantile spasms and autism. This study includes 90 patients who were diagnosed with infantile spasms at the Department of Pediatric Neurology in the Istanbul University Medical Faculty between 1995 and 2007. Of the 90 patients, 15 patients who were diagnosed with autism using the Autism Behaviour Checklist and Childhood Autism Rating Scale and a control group of nine patients without autism but with infantile spasms underwent PET examination. Mean patient age (± standard error, SE) varied between 3 years and 16 years (7.8 ± 4 years), while the mean follow-up time (±SE) varied between 2 years and 16 years (average: 7.1 ± 4 years). Autism was present in 11 patients with symptomatic spasms and in four patients with cryptogenic spasms (p=0.009). On the PET scans of the 15 patients with autism, 13 (86.7%) had significantly decreased metabolic activity in the temporal lobe (p<0.001), nine (60%) had significantly decreased activity in the frontal lobe (p=0.004), and seven (46.7%) had significantly decreased activity in the parietal lobe (p=0.022). In our opinion, hypometabolism in the frontal and parietal lobes, in addition to that previously reported in the temporal lobe, plays a role in the development of autism in patients with infantile spasms. PMID:23219829

  14. Reduced Visual Function Associated with Infantile Spasms in Children on Vigabatrin Therapy

    PubMed Central

    Hammoudi, Dena S.; Lee, Sophia S. F.; Madison, Adena; Mirabella, Giuseppe; Buncic, J. Raymond; Logan, William J.; Snead, O. Carter; Westall, Carol A.

    2013-01-01

    Purpose To use visual evoked potential (VEP) testing to determine whether visual deficits are present in children with a history of vigabatrin use. Methods Contrast sensitivity and visual acuity were assessed by visual evoked potential testing and compared between 28 children (mean age, 4.90 ± 4.92 years) with seizure disorders who had taken vigabatrin and 14 typically developing children (mean age, 3.14 ± 1.70 years). Exclusion criteria were heritable eye disease, suspected cortical visual impairment, nystagmus, and prematurity >2 weeks. The effects of the following factors on contrast sensitivity and visual acuity were examined: type of seizure (infantile spasms versus other), ERG result, duration of vigabatrin therapy, cumulative dosage of vigabatrin, and other seizure medications (other versus no other medication). Results Contrast sensitivity and visual acuity were reduced in vigabatrin-treated children with infantile spasms compared with vigabatrin-treated children with other seizure disorders and typically developing control subjects. The other factors examined had no significant effect on contrast sensitivity or visual acuity, with adjustment for seizure type. Conclusions Children with infantile spasms on vigabatrin may have compromised visual function, even in the absence of suspected cortical visual impairment. The children tested in the present study have reduced vision, probably associated with infantile spasms rather than vigabatrin. PMID:15671276

  15. Infantile Amnesia across the Years: A 2-Year Follow-Up of Children's Earliest Memories

    ERIC Educational Resources Information Center

    Peterson, Carole; Warren, Kelly L.; Short, Megan M.

    2011-01-01

    Although infantile amnesia has been investigated for many years in adults, only recently has it been investigated in children. This study was a 2-year follow-up and extension of an earlier study. Children (4-13 years old) were asked initially and 2 years later for their earliest 3 memories. At follow-up, their age at the time of these memories…

  16. Autoimmune Diseases in Parents of Children with Infantile Autism: A Case--Control Study

    ERIC Educational Resources Information Center

    Mouridsen, Svend Erik; Rich, Bente; Isager, Torben; Nedergaard, Niels Jorgen

    2007-01-01

    This register study compared the rates and types of autoimmune disease in the parents of 111 patients (82 males, 29 females; mean age at diagnosis 5y 5mo [SD 2y 6mo]) with infantile autism (IA) with a matched control group of parents of 330 children from the general population. All parents were screened through the nationwide Danish National…

  17. Molecular Correlates of Age-Dependent Seizures in an Inherited Neonatal-Infantile Epilepsy

    ERIC Educational Resources Information Center

    Liao, Yunxiang; Deprez, Liesbet; Maljevic, Snezana; Pitsch, Julika; Claes, Lieve; Hristova, Dimitrina; Jordanova, Albena; Ala-Mello, Sirpa; Bellan-Koch, Astrid; Blazevic, Dragica; Schubert, Simone; Thomas, Evan A.; Petrou, Steven; Becker, Albert J.; De Jonghe, Peter; Lerche, Holger

    2010-01-01

    Many idiopathic epilepsy syndromes have a characteristic age dependence, the underlying molecular mechanisms of which are largely unknown. Here we propose a mechanism that can explain that epileptic spells in benign familial neonatal-infantile seizures occur almost exclusively during the first days to months of life. Benign familial…

  18. Reduced Penetrance of PRRT2 Mutation in a Chinese Family With Infantile Convulsion and Choreoathetosis Syndrome.

    PubMed

    Zhang, L M; An, Y; Pan, G; Ding, Y F; Zhou, Y F; Yao, Y H; Wu, B L; Zhou, S Z

    2015-09-01

    Paroxysmal kinesigenic dyskinesia is a rare episodic movement disorder that can be isolated or associated with benign infantile seizures as part of choreoathetosis syndrome. Mutations in the PRRT2 gene have been recently identified as a cause of paroxysmal kinesigenic dyskinesia and infantile convulsion and choreoathetosis (ICCA). We reported a PRRT2 heterozygous mutation (c.604-607delTCAC, p.S202Hfs*25) in a 3-generation Chinese family with infantile convulsion and choreoathetosis and paroxysmal kinesigenic dyskinesia. The mutation was present in 5 family members, of which 4 were clinically affected and 1 was an obligate carrier with reduced penetrance of PRRT2. The affected carriers of this mutation presented with a similar type of infantile convulsion during early childhood and developed additional paroxysmal kinesigenic dyskinesia symptoms later in life. In addition, they all had a dramatic clinical response to oxcarbazepine/phenytoin therapy. Reduced penetrance of the PRRT2 mutation in this family could warrant genetic counseling. PMID:25403460

  19. On Human Symbiosis and the Vicissitudes of Individuation. Infantile Psychosis, Volume 1.

    ERIC Educational Resources Information Center

    Mahler, Margaret S.

    The concepts of symbiosis and separation-individuation are explained, and the symbiosis theory of infantile psychosis is presented. Diagnostic considerations and clinical cases of child psychosis are reviewed; prototypes of mother-child interaction are described; and therapy is discussed. A summary of the symbiosis theory and a bibliography of…

  20. Delayed-onset of multiple cutaneous infantile hemangiomas due to propranolol: a case report.

    PubMed

    Porcel Chacón, Rocío; del Boz González, Javier; Navarro Morón, Juan

    2015-04-01

    Infantile hemangiomas are the most common vascular tumors in childhood. In view of its proven effectiveness in such cases, propranolol is the drug of choice. We present the case of a male infant who started treatment with propranolol shortly after birth due to heart disease. After 7 months, when the patient had suffered various respiratory exacerbations, this treatment was suspended. One week later, multiple skin lesions (ie, multifocal infantile hemangiomas) began to appear, with no extracutaneous involvement. It was decided to resume treatment with propranolol, although at lower doses than before, and the skin lesions improved rapidly, with some disappearing completely. Treatment was definitively withdrawn at age 16 months, with only slight recurrence of the lesions. The case described is of multifocal infantile hemangiomas without extracutaneous involvement appearing beyond the neonatal period after treatment with propranolol beginning in the first days of life. The details of the case support the hypothesis that this drug is not only therapeutic but also plays a prophylactic role against infantile hemangiomas. In turn, this supports the recent proposal that this drug may be useful in preventing the growth and spread of tumors with high angiogenic potential. It is postulated that the inhibition of ?-adrenergic receptors is associated with multiple intracellular processes related to the progression and metastasis of different tumors. PMID:25780066

  1. Prenatal diagnosis of infantile myofibromatosis of the lung: a case report and review of the literature.

    PubMed

    Yeniel, Ahmet Ozgur; Ergenoglu, Ahmet Mete; Zeybek, Burak; Kazandi, Mert; Akercan, Fuat; Ozcan, Co?kun; Veral, Ali

    2013-01-01

    We present a case of infantile myofibromatosis of the lung detected at 32 weeks' gestation. The fetus was monitored with weekly ultrasound examinations measuring the mass size and amniotic fluid index. On day 2 after delivery, due to respiratory distress, an exploratory thoracotomy was undertaken and the mass was resected. PMID:23686518

  2. De novo KCNB1 mutations in infantile epilepsy inhibit repetitive neuronal firing

    PubMed Central

    Saitsu, Hirotomo; Akita, Tenpei; Tohyama, Jun; Goldberg-Stern, Hadassa; Kobayashi, Yu; Cohen, Roni; Kato, Mitsuhiro; Ohba, Chihiro; Miyatake, Satoko; Tsurusaki, Yoshinori; Nakashima, Mitsuko; Miyake, Noriko; Fukuda, Atsuo; Matsumoto, Naomichi

    2015-01-01

    The voltage-gated Kv2.1 potassium channel encoded by KCNB1 produces the major delayed rectifier potassium current in pyramidal neurons. Recently, de novo heterozygous missense KCNB1 mutations have been identified in three patients with epileptic encephalopathy and a patient with neurodevelopmental disorder. However, the frequency of KCNB1 mutations in infantile epileptic patients and their effects on neuronal activity are yet unknown. We searched whole exome sequencing data of a total of 437 patients with infantile epilepsy, and found novel de novo heterozygous missense KCNB1 mutations in two patients showing psychomotor developmental delay and severe infantile generalized seizures with high-amplitude spike-and-wave electroencephalogram discharges. The mutation located in the channel voltage sensor (p.R306C) disrupted sensitivity and cooperativity of the sensor, while the mutation in the channel pore domain (p.G401R) selectively abolished endogenous Kv2 currents in transfected pyramidal neurons, indicating a dominant-negative effect. Both mutants inhibited repetitive neuronal firing through preventing production of deep interspike voltages. Thus KCNB1 mutations can be a rare genetic cause of infantile epilepsy, and insufficient firing of pyramidal neurons would disturb both development and stability of neuronal circuits, leading to the disease phenotypes. PMID:26477325

  3. Phenotypical Characteristics of Idiopathic Infantile Nystagmus with and without Mutations in "FRMD7"

    ERIC Educational Resources Information Center

    Thomas, Shery; Proudlock, Frank A.; Sarvananthan, Nagini; Roberts, Eryl O.; Awan, Musarat; McLean, Rebecca; Surendran, Mylvaganam; Kumar, A. S. Anil; Farooq, Shegufta J.; Degg, Chris; Gale, Richard P.; Reinecke, Robert D.; Woodruff, Geoffrey; Langmann, Andrea; Lindner, Susanne; Jain, Sunila; Tarpey, Patrick; Raymond, F. Lucy; Gottlob, Irene

    2008-01-01

    Idiopathic infantile nystagmus (IIN) consists of involuntary oscillations of the eyes. The familial form is most commonly X-linked. We recently found mutations in a novel gene "FRMD7" (Xq26.2), which provided an opportunity to investigate a genetically defined and homogeneous group of patients with nystagmus. We compared clinical features and eye…

  4. [Infantile pyknocytosis: A cause of noenatal hemolytic anemia. Is recombinant erythropoietin an alternative to transfusion?].

    PubMed

    Bagou, M; Rolland, E; Gay, C; Patural, H

    2016-01-01

    Infantile pyknocytosis is a neonatal hemolytic disorder which causes anemia and icterus and is characterized by the presence of an increased number of distorted red blood cells called pyknocytes. Resolution spontaneously occurs in the first semester of life. It has been generally described as a rare entity, with an occasional family history. We report seven cases of infantile pyknocytosis observed in our hospital in 3years. Most of the infants presented with hemolytic icterus and profound anemia that was reaching its peak by the 3rd week of life. Three neonates received one to three red blood cell transfusions, according to former recommendations. However, the following four received a treatment with recombinant erythropoietin administered subcutaneously. Only one of these four cases required a transfusion. All of them were free of hematological disease 2-3months after completion of treatment. Infantile pyknocytosis is a recognized cause of neonatal hemolytic anemia, which requires careful examination of red cell morphology on a peripheral blood smear. The cause of this transient disorder remains unknown. Our observations show that recombinant erythropoietin therapy is effective in treating infantile pyknocytosis and increases the reticulocyte response, thus improving the hemoglobin level. PMID:26563723

  5. Malignant Melanoma Clinically Masquerading Vascular Tumor: A Diagnostic Dilemma

    PubMed Central

    Pradhan, Samiksha; Sancheti, Karan; Podder, Indrashis; Gharami, Ramesh Chandra

    2015-01-01

    Malignant melanoma is an invasive neoplasm of the skin, whose incidence is reported to be rising among Indians. We hereby present a unique case of unilateral, multiple, asymptomatic, pigmented, nodular lesions over the lower limb; resembling vascular tumor, revealing itself as malignant melanoma only on histopathology. To the best of our knowledge, such a unique presentation of malignant melanoma has not yet been reported from the Indian subcontinent. PMID:26677278

  6. Postirradiation sarcoma (malignant fibrous histiocytoma) following cervix cancer

    SciTech Connect

    Pinkston, J.A.; Sekine, I.

    1982-02-01

    A case of postirradiation sarcoma is described. The tumor, a malignant fibrous histiocytoma, occurred in the radiation field 11 years following postoperative external beam radiation therapy (7000 rad) for carcinoma of the cervix. Reports of postirradiation malignant fibrous histiocytoma are rare, and the occurrence of this neoplasm following treatment of cervix cancer has not previously been described. The literature concerning postirradiation bone and soft tissue sarcomas is briefly reviewed, with special attention to malignant fibrous histiocytomas.

  7. Preoperative Evaluation of Risk of Ovarian Malignancy Algorithm Index in Prediction of Malignancy of Adnexal Masses

    PubMed Central

    Farzaneh, Farah; Honarvar, Zahra; Yaraghi, Mansoore; Yaseri, Mehdi; Arab, Maliheh; Hosseini, Maryamsadat; Ashrafgangoi, Tahereh

    2014-01-01

    Background: Differentiation between benign and malignant ovarian neoplasms is essential to create a system for patient referrals. Objectives: The aim of the present prospective trial was to analyze the value of the risk of ovarian malignancy algorithm (ROMA) in prediction of adnexal masses malignancy in pre- and post-menopause women before operation. Materials and Methods: Preoperative serum samples were tested for CA125 and HE4 using fully automated methods (Abbott architect) and gained best cutoff. The ROMA index was analyzed in 99 patients (including 68 pre-menopause and 31 menopause) with adnexal masses referred to Imam Hossein Hospital/Tehran/Iran and had been scheduled for operation. The pathological results showed 43 cases (22 menopause) with malignant adnexal masses and 56 cases (9 menopauses) with benign adnexal masses. Demographical data, clinical symptoms and the ROMA index were separately analyzed and contrasted in benign and malignant in both menopause and pre-menopause patients. Results: The only significant difference was the older age of the malignant group vs. benign group (P = 0.001) regarding demographic findings. As concerns the clinical symptoms, presence of abdominal discomfort in pre-diagnosis period was the only significant parameter in malignant group (P = 0.001). Additionally, data analysis of patients as a total group showed that specificity (96.4%), positive predictive value (PPV) (94.1%), area under the curve (AUC) (0.907), and diagnostic accuracy (DA) (86.9%) of the ROMA were higher than HE4 (91.1%, 85.7%, 0.857 and 81.8%. respectively) and CA125 (87.9%, 67.3%, 0.828 and 75.8%, respectively) alone. Besides, negative predictive value (NPV) (86.4%) and sensitivity (86.1%) of CA125 were higher than HE4 (79.7% and 69.8%, respectively). In contrast, specificity of HE4 (91.1%) was higher than CA125 (67.9%). Data analysis of patients as two groups (pre and post menopause groups) showed the same results. Conclusions: Specificity, DA and AUC of the ROMA were higher than HE4 and CA125 taken separately. PMID:25068046

  8. MicroRNA-155 and Its Role in Malignant Hematopoiesis

    PubMed Central

    Ranganath, Prajnya

    2015-01-01

    MicroRNA-155 (miR-155) is a multifunctional molecule involved in both normal and malignant hematopoiesis. It has been found to be involved in the pathogenesis of many different hematological malignancies with either an oncogenic or a tumor-repressor effect, depending on the nature of the cell and the type of malignancy. In particular, it has been strongly implicated in the causation of diffuse large B-cell lymphomas. This review focuses on the molecular interactions of miR-155, its oncogenic mechanisms, and its potential as an effective therapeutic target for the associated malignancies. PMID:26523117

  9. [Peritoneal malignant mesothelioma: review and recent data].

    PubMed

    Mery, Éliane; Hommell-Fontaine, Juliette; Capovilla, Mathieu; Chevallier, Anne; Bibeau, Frédéric; Croce, Sabrina; Dartigues, Peggy; Kaci, Rachid; Lang-Averous, Gerlinde; Laverriere, Marie-Hélène; Leroux-Broussier, Agnès; Poizat, Flora; Robin, Nina; Valmary-Degano, Séverine; Verriele-Beurrier, Véronique; Villeneuve, Laurent; Isaac, Sylvie

    2014-02-01

    Peritoneal malignant mesothelioma is a rare tumor, less common than its pleural counterpart. It develops from the mesothelial cells overlying peritoneum and preferentially occurs in male, with an average age ranging from 47 to 60.5 years. Asbestos whose impact is less strong than in pleural mesothelioma, SV 40 virus, chronic peritonitis could be implicated as factors favoring the development of peritoneal mesothelioma. Clinical symptoms are not specific, and the imagery remains little or not contributive. The 2004 WHO classification recognizes 3 different types, which differ in terms of presentation and prognosis: diffuse epithelioid mesothelioma (the most common), sarcomatoid mesothelioma and biphasic mesothelioma. Many variants are described within these groups. Immunohistochemistry is mandatory to affirm or disprove peritoneal malignant mesothelioma diagnosis, based on a panel of antibodies divided in positive markers and negative markers. Indeed an accurate diagnosis is necessary to define a therapeutic strategy more and more frequently based on the combination of radical surgery and hyperthermic intra peritoneal chemotherapy. Such an approach significantly improves the prognosis of these aggressive diseases. PMID:24630634

  10. Leptomeningeal metastasis from supratentorial malignant gliomas.

    PubMed

    Awad, I; Bay, J W; Rogers, L

    1986-08-01

    The clinical and diagnostic findings in 13 patients with leptomeningeal metastasis from supratentorial malignant gliomas are reported. Criteria for inclusion in this study were positive myelographic examination, positive cerebrospinal fluid cytology on two or more samples, or evidence of leptomeningeal seeding at autopsy. Eight patients had premortem symptoms of leptomeningeal metastasis, with the diagnosis confirmed during life in 5 patients. Average survival after the onset of symptoms was 3 months (range, 1 to 5 months). Comparison of the autopsied group with 10 concurrent autopsied patients without leptomeningeal gliomatosis did not reveal any significant differences in age, but leptomeningeal gliomatosis was more prevalent in patients with longer postoperative survival. Leptomeningeal involvement at autopsy was more extensive in symptomatic patients. Cerebrospinal fluid examination often gave nondiagnostic or nonspecific results. Computed tomography of the brain showed evidence of ventriculomegaly, periventricular contrast enhancement, or multifocal tumor involvement in every case. Iophendylate myelography was the most reliable diagnostic tool and established the diagnosis whenever performed. The natural history and clinical significance of leptomeningeal metastasis from supratentorial malignant gliomas are discussed. PMID:3748352

  11. Preoperative cutaneous lymphoscintigraphy in malignant melanoma

    SciTech Connect

    Lock-Andersen, J.; Rossing, N.; Drzewiecki, K.T.

    1989-01-01

    To identify the regional lymph node basins cutaneous lymphoscintigraphy with technetium 99m rhenium sulfide colloid (/sup 99m/Tc-ReS) was performed in 45 patients and with technetium 99m antimony sulfide colloid (/sup 99m/Tc-Sb2S3) in seven patients after excisional biopsy of the primary tumor. All patients had skin tumors located in the face or neck or on the trunk with 47 cases of cutaneous malignant melanoma and 5 cases of benign or premalignant lesions. In 48 patients the scintiscans 1 hour after perilesional injection of the tracer colloid clearly showed the lymphatic drainage patterns from the tumor sites, of them 25 patients demonstrated unidirectional drainage, whereas the remaining 23 patients had multidirectional drainage to two or three lymph node groups. There were technical difficulties in performing the examinations in four patients. The authors recommend cutaneous lymphoscintigraphy as a safe, simple and reliable technique for mapping the lymphatic drainage preoperatively in patients with Stage I cutaneous malignant melanoma of axial localization.

  12. Nanotechnology applications in hematological malignancies (Review).

    PubMed

    Samir, Ahmed; Elgamal, Basma M; Gabr, Hala; Sabaawy, Hatem E

    2015-09-01

    A major limitation to current cancer therapies is the development of therapy-related side-effects and dose limiting complications. Moreover, a better understanding of the biology of cancer cells and the mechanisms of resistance to therapy is rapidly developing. The translation of advanced knowledge and discoveries achieved at the molecular level must be supported by advanced diagnostic, therapeutic and delivery technologies to translate these discoveries into useful tools that are essential in achieving progress in the war against cancer. Nanotechnology can play an essential role in this aspect providing a transforming technology that can translate the basic and clinical findings into novel diagnostic, therapeutic and preventive tools useful in different types of cancer. Hematological malignancies represent a specific class of cancer, which attracts special attention in the applications of nanotechnology for cancer diagnosis and treatment. The aim of the present review is to elucidate the emerging applications of nanotechnology in cancer management and describe the potentials of nanotechnology in changing the key fundamental aspects of hematological malignancy diagnosis, treatment and follow-up. PMID:26134389

  13. Nanotechnology applications in hematological malignancies (Review)

    PubMed Central

    SAMIR, AHMED; ELGAMAL, BASMA M; GABR, HALA; SABAAWY, HATEM E

    2015-01-01

    A major limitation to current cancer therapies is the development of therapy-related side-effects and dose limiting complications. Moreover, a better understanding of the biology of cancer cells and the mechanisms of resistance to therapy is rapidly developing. The translation of advanced knowledge and discoveries achieved at the molecular level must be supported by advanced diagnostic, therapeutic and delivery technologies to translate these discoveries into useful tools that are essential in achieving progress in the war against cancer. Nanotechnology can play an essential role in this aspect providing a transforming technology that can translate the basic and clinical findings into novel diagnostic, therapeutic and preventive tools useful in different types of cancer. Hematological malignancies represent a specific class of cancer, which attracts special attention in the applications of nanotechnology for cancer diagnosis and treatment. The aim of the present review is to elucidate the emerging applications of nanotechnology in cancer management and describe the potentials of nanotechnology in changing the key fundamental aspects of hematological malignancy diagnosis, treatment and follow-up. PMID:26134389

  14. [Surgical intervention in patients with malignant glioma].

    PubMed

    Kostron, Herwig; Rössler, Karl

    2006-06-01

    Glial tumors occur at an incidence from 2 to 10/ 100.000 (Japan vs. Sweden) and building up to 50 % of all patients suffering from brain tumors. 50 % of those are again malignant gliomas Grade III and Grade IV. Despite all therapeutic approaches the median survival for glioblastomas is 15 months and for anaplastic gliomas Grade III 30 months. After diagnosis, preferably by MRI, a neurosurgical procedure is performed under microsurgical guidelines mostly by means of neuronavigation and intraoperative guidance. Depending on the preoperative diagnosis and localisation of the pathologic lesion an open craniotomy or a stereotactic biopsy is performed. This allows the histological verification and decompression and cytoreduction. A gros total safe removal preserving neurological function is the most important goal of surgery. Tumor removal in eloquent areas such as speech area is performed under local anesthesia as an awake operation. Age, Karnofsky performance status, histology as well as radical removal have a significant influence on overall survival. Adjuvant radiotherapy and chemotherapy with Temozolemide have further improved the outcome significantly. The 2-year survival has reached 28 % in most recent studies. Further experimental therapies in controlled trials, such as intratumoral convection-enhanced instillation of immunotoxins and radiopeptids, photodynamic therapy and direct instillation of new formulations of chemotherapeutic drugs (e. g. nanoparticles) are promising new approaches. New developments in the treatment of patients harboring malignant brain tumors allow an individual neurooncological treatment concept to be established to enhance overall survival and quality of life. PMID:16944364

  15. Myeloid malignancies: mutations, models and management

    PubMed Central

    2012-01-01

    Myeloid malignant diseases comprise chronic (including myelodysplastic syndromes, myeloproliferative neoplasms and chronic myelomonocytic leukemia) and acute (acute myeloid leukemia) stages. They are clonal diseases arising in hematopoietic stem or progenitor cells. Mutations responsible for these diseases occur in several genes whose encoded proteins belong principally to five classes: signaling pathways proteins (e.g. CBL, FLT3, JAK2, RAS), transcription factors (e.g. CEBPA, ETV6, RUNX1), epigenetic regulators (e.g. ASXL1, DNMT3A, EZH2, IDH1, IDH2, SUZ12, TET2, UTX), tumor suppressors (e.g. TP53), and components of the spliceosome (e.g. SF3B1, SRSF2). Large-scale sequencing efforts will soon lead to the establishment of a comprehensive repertoire of these mutations, allowing for a better definition and classification of myeloid malignancies, the identification of new prognostic markers and therapeutic targets, and the development of novel therapies. Given the importance of epigenetic deregulation in myeloid diseases, the use of drugs targeting epigenetic regulators appears as a most promising therapeutic approach. PMID:22823977

  16. Patterns of second malignant neoplasms in children.

    PubMed

    Meadows, A T; D'Angio, G J; Miké, V; Banfi, A; Harris, C; Jenkin, R D; Schwartz, A

    1977-10-01

    A search of the records of 10 pediatric oncology centers revealed 102 children with more than one malignant neoplasm. In this group of 102 patients, all pediatric cancers were seen as initial lesions, but Wilms' tumor and retinoblastoma were over-represented and leukemia and brain tumors underrepresented. Survival variation as well as tumor susceptibility may be responsible for this disproportion. Osteosarcomas and chondrosarcomas were the most frequent second malignant neoplasms (SMN). Embryonal tumors were rare as SMN and adult-type tumors (carcinomas) appeared at earlier than expected ages, whether arising after irradiation or not related to that form of therapy. Radiation was associated with 69 SMN, genetic disease accounted for 27 SMN and both conditions were noted in 15 SMN. In the group of 21 patients for whom neither radiation nor a known genetic disorder could be implicated, there were three with colon carcinoma and glioma and five with leukemia or lymphoma and glioma. These combinations may reflect new tissue-specific hereditary cancer syndromes. PMID:198110

  17. Role of Extracellular Vesicles in Hematological Malignancies

    PubMed Central

    Raimondo, Stefania; Corrado, Chiara; Raimondi, Lavinia; De Leo, Giacomo; Alessandro, Riccardo

    2015-01-01

    In recent years the role of tumor microenvironment in the progression of hematological malignancies has been widely recognized. Recent studies have focused on how cancer cells communicate within the microenvironment. Among several factors (cytokines, growth factors, and ECM molecules), a key role has been attributed to extracellular vesicles (EV), released from different cell types. EV (microvesicles and exosomes) may affect stroma remodeling, host cell functions, and tumor angiogenesis by inducing gene expression modulation in target cells, thus promoting cancer progression and metastasis. Microvesicles and exosomes can be recovered from the blood and other body fluids of cancer patients and contain and deliver genetic and proteomic contents that reflect the cell of origin, thus constituting a source of new predictive biomarkers involved in cancer development and serving as possible targets for therapies. Moreover, due to their specific cell-tropism and bioavailability, EV can be considered natural vehicles suitable for drug delivery. Here we will discuss the recent advances in the field of EV as actors in hematological cancer progression, pointing out the role of these vesicles in the tumor-host interplay and in their use as biomarkers for hematological malignancies. PMID:26583135

  18. Ultrastructure of human malignant diffuse mesothelioma.

    PubMed Central

    Suzuki, Y.; Kannerstein, M.

    1976-01-01

    Eleven cases of malignant diffuse mesotheliomas, histologically classified into two groups, epithelial (5 pleural and 3 peritoneal) and biphasic or mixed (2 pleural and 1 peritoneal) forms, were stuied by electron microscopy to elucidate their ultrastructural characteristics. The neoplastic cells of the epithelial forms were varied in ultrastructure, from well differentiated (marked by polarity, micovilli, glycogen granules, junctional structures, tonofilaments, intracellular vacuoles, and a basement membrane) to poorly differentiated (which lacked some of these epithelial characteristics). In four of eight instances in epithelial type tumors, nonepithelial or mesenchymal neoplastic cells were recognized. The biphasic or mixed cases included three major cell types: epithelial, atypical epithelial, and mesenchymal. It appeared that there were transitional forms among the three cell types. The observations support the concept that the neoplastic cell of malignant mesothelioma can differentiate into a number of cell lines. Images Figures 20 and 21 Figure 22 Figure 23 Figures 24 and 25 Figure 26 Figure 27A Figure 27B and C Figure 28 Figure 29 Figure 30 Figure 31 Figures 32 and 33 Figure 34 Figure 35 Figure 36 Figures 1-4 Figures 5 and 6 Figure 37 Figures 7-10 Figure 11 Figure 12 Figure 13 Figure 14 Figure 15 Figure 16 Figures 17 and 18 Figure 19 PMID:998721

  19. Cladribine for the treatment of hematologic malignancies.

    PubMed

    Baltz, J K; Montello, M J

    1993-11-01

    The mechanism of action, pharmacokinetics, efficacy, adverse effects, storage, dosage and administration, and cost of cladribine are reviewed. Cladribine (2-chloro-2'-deoxyadenosine) is a synthetic purine nucleoside developed for the treatment of hematologic malignancies. It appears that cladribine interferes with lymphocyte proliferation by inhibiting DNA repair. The pharmacokinetics of cladribine best fit a two-compartment, first-order-elimination model. Of the conditions that have been treated with cladribine, hairy cell leukemia (HCL) has shown the most dramatic response. Overall response rates in clinical studies have ranged from 80% to 100%, with a large majority of these being complete remissions; median durations of responses have ranged from about 9 to 16 months. Other conditions that have responded to cladribine are chronic lymphocytic leukemia (CLL), acute leukemia, chronic myeloid leukemia, low-grade lymphomas, Waldenström's macroglobulinemia, and cutaneous T-cell lymphoma. The drug is inactive against solid tumors. The principal dose-limiting adverse effect of cladribine is bone marrow suppression; fever, immunosuppression, renal and neurologic effects, and local skin reactions have also been reported. The drug is typically administered as an extended continuous i.v. infusion. The usual dosage for treating HCL is 0.1 mg/kg/day for seven days. The estimated cost of cladribine for treating an average patient with HCL is $3500. Cladribine has shown efficacy against a variety of hematologic malignancies, notably HCL and CLL. PMID:7903917

  20. Genetic heterogeneity in neuronal ceroid lipofuscinosis (NCL): Evidence that the late-infantile subtype (Jansky-Bielschowsky disease; CLN2) is not an allelic form of the juvenile or infantile subtypes

    SciTech Connect

    Williams, R.; McKay, T.; Mitchison, H.; Gardiner, M. ); Vesa, J.; Jaervelae, I.; Hellsten, E.; Peltonen, L.; Thompson, A.; Callen, D.; Sutherland, G.; Luna-Battadano, D.; Stallings, R.

    1993-10-01

    The neuronal ceroid lipofuscinoses (NCLs) are a group of inherited neurodegenerative disorders characterized by the accumulation of autofluorescent lipopigment in neurons and other cell types. Inheritance is autosomal recessive. Three main childhood subtypes are recognized: Infantile (Haltia-Santavuori disease; MIM 256743), late infantile (Jansky-Bielschowsky disease; MIM 204500), and juvenile (Spielmeyer-Sjoegren-Vogt, or Batten disease; MIM 204200). The gene loci for the juvenile (CLN3) and infantile (CLN1) types have been mapped to human chromosomes 16p and 1p, respectively, by linkage analysis. Linkage analysis of 25 families segregating for late-infantile NCL has excluded these regions as the site of this disease locus (CLN2). The three childhood subtypes of NCL therefore arise from mutations at distinct loci. 17 refs., 2 figs., 3 tabs.

  1. Hedgehog Signaling in Malignant Pleural Mesothelioma

    PubMed Central

    Felley-Bosco, Emanuela; Opitz, Isabelle; Meerang, Mayura

    2015-01-01

    Malignant pleural mesothelioma (MPM) is a cancer associated with exposure to asbestos fibers, which accumulate in the pleural space, damage tissue and stimulate regeneration. Hedgehog signaling is a pathway important during embryonic mesothelium development and is inactivated in adult mesothelium. The pathway is reactivated in some MPM patients with poor clinical outcome, mainly mediated by the expression of the ligands. Nevertheless, mutations in components of the pathway have been observed in a few cases. Data from different MPM animal models and primary culture suggest that both autocrine and paracrine Hedgehog signaling are important to maintain tumor growth. Drugs inhibiting the pathway at the level of the smoothened receptor (Smo) or glioma-associated protein transcription factors (Gli) have been used mostly in experimental models. For clinical development, biomarkers are necessary for the selection of patients who can benefit from Hedgehog signaling inhibition. PMID:26184317

  2. Tribbles in normal and malignant haematopoiesis

    PubMed Central

    Stein, Sarah J.; Mack, Ethan A.; Rome, Kelly S.; Pear, Warren S.

    2015-01-01

    The tribbles protein family, an evolutionarily conserved group of pseudokinases, have been shown to regulate multiple cellular events including those involved in normal and malignant haematopoiesis. The three mammalian Tribbles homologues, Trib1, Trib2 and Trib3 are characterized by conserved motifs, including a pseudokinase domain and a C-terminal E3 ligase-binding domain. In this review, we focus on the role of Trib (mammalian Tribbles homologues) proteins in mammalian haematopoiesis and leukaemia. The Trib proteins show divergent expression in haematopoietic cells, probably indicating cell-specific functions. The roles of the Trib proteins in oncogenesis are also varied and appear to be tissue-specific. Finally, we discuss the potential mechanisms by which the Trib proteins preferentially regulate these processes in multiple cell types. PMID:26517933

  3. Malignant peripheral nerve sheath tumour of penis.

    PubMed

    Kaur, J; Madan, R; Singh, L; Sharma, D N; Julka, P K; Rath, G K; Roy, S

    2015-04-01

    Malignant peripheral nerve sheath tumour (MPNST) is a rare variety of soft tissue sarcoma that originates from Schwann cells or pluripotent cells of neural crest origin. They have historically been difficult tumours to diagnose and treat. Surgery is the mainstay of treatment with a goal to achieve negative margins. Despite aggressive surgery and adjuvant therapy, the prognosis of patients with MPNST remains poor. MPNST arising from penis is a very rare entity; thus, it presents a diagnostic and therapeutic challenge. We present a case of penile MPNST in a 38-year-old man in the absence of neurofibromatosis treated with surgery followed by post-operative radiotherapy to a dose of 60 Gray in 30 fractions and adjuvant chemotherapy with ifosfamide and adriamycin. PMID:24635732

  4. Autophagy in malignant transformation and cancer progression.

    PubMed

    Galluzzi, Lorenzo; Pietrocola, Federico; Bravo-San Pedro, José Manuel; Amaravadi, Ravi K; Baehrecke, Eric H; Cecconi, Francesco; Codogno, Patrice; Debnath, Jayanta; Gewirtz, David A; Karantza, Vassiliki; Kimmelman, Alec; Kumar, Sharad; Levine, Beth; Maiuri, Maria Chiara; Martin, Seamus J; Penninger, Josef; Piacentini, Mauro; Rubinsztein, David C; Simon, Hans-Uwe; Simonsen, Anne; Thorburn, Andrew M; Velasco, Guillermo; Ryan, Kevin M; Kroemer, Guido

    2015-04-01

    Autophagy plays a key role in the maintenance of cellular homeostasis. In healthy cells, such a homeostatic activity constitutes a robust barrier against malignant transformation. Accordingly, many oncoproteins inhibit, and several oncosuppressor proteins promote, autophagy. Moreover, autophagy is required for optimal anticancer immunosurveillance. In neoplastic cells, however, autophagic responses constitute a means to cope with intracellular and environmental stress, thus favoring tumor progression. This implies that at least in some cases, oncogenesis proceeds along with a temporary inhibition of autophagy or a gain of molecular functions that antagonize its oncosuppressive activity. Here, we discuss the differential impact of autophagy on distinct phases of tumorigenesis and the implications of this concept for the use of autophagy modulators in cancer therapy. PMID:25712477

  5. Ablative Therapies for Colorectal Polyps and Malignancy

    PubMed Central

    Hochwald, Steven N.; Nurkin, Steven

    2014-01-01

    Endoscopic techniques are gaining popularity in the management of colorectal polyps and occasionally superficial cancers. While their use is in many times palliative, they have proven to be curative in carefully selected patients with polyps or malignancies, with less morbidity than radical resection. However, one should note that data supporting local and ablative therapies for colorectal cancer is scarce and may be subject to publication bias. Therefore, for curative intent, these techniques should only be considered in highly select cases as higher rates of local recurrences have also been reported. The aim of this review is to explain the different modalities of local and ablative therapies specific to colorectal neoplasia and explain the indications and circumstances where they have been most successful. PMID:25089281

  6. Spontaneous Regression of Metastatic Visceral Malignant Melanoma

    PubMed Central

    Haight, Kenneth R.; Shapira, David V.; Cates, Geoffrey W.

    1984-01-01

    Spontaneous regressions of malignant tumors are rare. This report describes a patient who, after local recurrence of melanoma in his neck, developed pulmonary metastases which subsequently regressed. The patient was a 72-year-old retired farmer. Over the four years and five months from the discovery of the metastases to his death, this patient's pulmonary nodules regressed. Treatment was palliative, and there is no evidence that his immune system was artificially stimulated. He died from complications of a surgical repair of a hiatus hernia. No increase in the size of the pulmonary nodules was noted in chest X-rays taken during the three months before his death. ImagesFig. 1Fig. 2Fig. 3Fig. 4Fig. 5Fig. 6Fig. 7Fig. 8 PMID:21278950

  7. Malignant thoracopulmonary small-cell (Askin) tumor

    SciTech Connect

    Fink, I.J.; Kurtz, D.W.; Cazenave, L.; Lieber, M.R.; Miser, J.S.; Chandra, R.; Triche, T.J.

    1985-09-01

    The clinical, radiographic, and pathologic features of 10 patients with documented malignant small-cell tumor of the thoracopulmonary region (Askin tumor) were reviewed. The tumor represents a distinct pathologic entity of neuroectodermal origin. Clinically, it presents as a chest-wall mass with or without pain. Its radiographic appearance is that of a soft-tissue mass with or without pleural or rib involvement, often with metastatic disease - to the skeletal system, bone marrow, thorax, and sympathetic chain. Two patients developed metastases to the adrenal gland and liver, one after autologous bone marrow transplantation. The radiologist should be aware of this entity and its pattern of metastatic spread since metastases are treated aggressively.

  8. CNS effects following the treatment of malignancy.

    PubMed

    Rane, N; Quaghebeur, G

    2012-01-01

    Corporeal and central nervous system (CNS) axis chemotherapy and radiotherapy have long been used for the effective treatment and prophylaxis of CNS, body malignancies, and leukaemias. However, they are not without their problems. Following the proliferation of magnetic resonance neuroimaging in recent years it has become clear that the spectrum of toxicity that these therapies produce ranges from subclinical white matter changes to overt brain necrosis. The effects are both direct and indirect and via different pathological mechanisms. Chronic and progressive changes can be detected many years after the initial intervention. In addition to leucoencephalopathic changes, grey matter changes are now well described. Changes may be difficult to distinguish from tumour recurrence, though may be reversible and remediable, and are thus very important to differentiate. In this review toxic effects are classified and their imaging appearances discussed, with reference to specific syndromes. PMID:22055261

  9. Minimal invasive treatments for liver malignancies.

    PubMed

    Orsi, Franco; Varano, Gianluca

    2015-11-01

    Minimal invasive therapies have proved useful in the management of primary and secondary hepatic malignancies. The most relevant aspects of all these therapies are their minimal toxicity profiles and highly effective tumor responses without affecting the normal hepatic parenchyma. These unique characteristics coupled with their minimally invasive nature provide an attractive therapeutic option for patients who previously may have had few alternatives. Combination of these therapies might extend indications to bring curative treatment to a wider selected population. The results of various ongoing combination trials of intraarterial therapies with targeted therapies are awaited to further improve survival in this patient group. This review focuses on the application of ablative and intra-arterial therapies in the management of hepatocellular carcinoma and hepatic colorectal metastasis. PMID:26050603

  10. Expanding role of lenalidomide in hematologic malignancies

    PubMed Central

    Ghosh, Nilanjan; Grunwald, Michael R; Fasan, Omotayo; Bhutani, Manisha

    2015-01-01

    Lenalidomide is an immunomodulatory agent that has been approved by the US Food and Drug Administration for treatment of multiple myeloma, deletion 5q myelodysplastic syndrome, and mantle cell lymphoma. In addition, it has clinical activity in lymphoproliferative disorders and acute myeloid leukemia. The mode of action includes immunomodulatory, anti-inflammatory, antiangiogenic, and antiproliferative mechanisms. The antitumor effect is a result of direct interference of key pathways in tumor cells and indirect modulation of the tumor microenvironment. There has been no recent collective review on lenalidomide in multiple myeloma, myelodysplastic syndrome/acute myeloid leukemia, and lymphoma. This review summarizes the results of current clinical studies of lenalidomide, alone and in combination with other agents, as a therapeutic option for various hematologic malignancies. PMID:25999761

  11. Therapeutic node dissections in malignant melanoma.

    PubMed

    Karakousis, C P

    1998-06-01

    In the absence of distant disease, therapeutic node dissections in malignant melanoma, i.e., dissections of regional nodal basins for palpable suspicious or biopsy-proven positive nodes, offer the chance of cure. The 5-year survival rates after therapeutic lymphadenectomy closely correlate with expected cure rates. Although they varied greatly in the literature, from 19% to 38%, the currently obtainable survival rates are in the upper ranges of this spectrum because patients now are closely followed-up and operated for early palpable nodal disease. Properly done, these procedures carry a low morbidity, but they should be done thoroughly to completely eradicate regional disease and avoid recurrences in the same nodal basin to achieve the maximum survival that is surgically attainable. PMID:9588722

  12. Cap-Independent Translation in Hematological Malignancies

    PubMed Central

    Horvilleur, Emilie; Wilson, Lindsay A.; Bastide, Amandine; Piñeiro, David; Pöyry, Tuija A. A.; Willis, Anne E.

    2015-01-01

    Hematological malignancies are a heterogeneous group of diseases deriving from blood cells progenitors. Although many genes involved in blood cancers contain internal ribosome entry sites (IRESes), there has been only few studies focusing on the role of cap-independent translation in leukemia and lymphomas. Expression of IRES trans-acting factors can also be altered, and interestingly, BCL-ABL1 fusion protein expressed from “Philadelphia” chromosome, found in some types of leukemia, regulates several of them. A mechanism involving c-Myc IRES and cap-independent translation and leading to resistance to chemotherapy in multiple myeloma emphasize the contribution of cap-independent translation in blood cancers and the need for more work to be done to clarify the roles of known IRESes in pathology and response to chemotherapeutics.

  13. Tribbles in normal and malignant haematopoiesis.

    PubMed

    Stein, Sarah J; Mack, Ethan A; Rome, Kelly S; Pear, Warren S

    2015-10-01

    The tribbles protein family, an evolutionarily conserved group of pseudokinases, have been shown to regulate multiple cellular events including those involved in normal and malignant haematopoiesis. The three mammalian Tribbles homologues, Trib1, Trib2 and Trib3 are characterized by conserved motifs, including a pseudokinase domain and a C-terminal E3 ligase-binding domain. In this review, we focus on the role of Trib (mammalian Tribbles homologues) proteins in mammalian haematopoiesis and leukaemia. The Trib proteins show divergent expression in haematopoietic cells, probably indicating cell-specific functions. The roles of the Trib proteins in oncogenesis are also varied and appear to be tissue-specific. Finally, we discuss the potential mechanisms by which the Trib proteins preferentially regulate these processes in multiple cell types. PMID:26517933

  14. Ephs and Ephrins in Malignant Gliomas

    PubMed Central

    Ferluga, Sara; Debinski, Waldemar

    2015-01-01

    Eph receptor tyrosine kinases and the corresponding ephrin ligands play a pivotal role in glioma development and progression. Aberrant protein expression levels of the Eph receptors and ephrins are often associated with higher tumor grade and poor prognosis. Their function in tumorigenesis is complex due to the intricate network of possible co-occurring interactions between neighboring tumor cells and tumor microenvironment. Both Ephs and ephrins localize on the surface of tumor cells, tumor vasculature, glioma stem cells tumor cells infiltrating brain and immune cells infiltrating tumors. They can both promote and inhibit tumorigenicity depending on the downstream forward and reverse signalling generated. All the above-mentioned features make the Ephs/ephrins system an intriguing candidate for the development of new therapeutic strategies in glioma treatment. This review will give a general overview on structure and function of Ephs and ephrins, with particular emphasis on the state-of-the-knowledge of their role in malignant gliomas. PMID:25418012

  15. Malignant pleural mesothelioma: an epidemiological perspective

    PubMed Central

    2012-01-01

    This paper reviews the aetiology, distribution and projected future incidence of malignant mesothelioma. Asbestos exposure is the most thoroughly established risk factor. Debate continues regarding the relative importance of the different asbestos fibre types and the contribution of Simian virus 40 (SV40). Disease incidence varies markedly within and between countries. The highest annual rates of disease, approximately 30 case per million, are reported in Australia and Great Britain. The risk of disease increases with age and is higher in men. Time from asbestos exposure to disease diagnosis is on average greater than 40 years. Non-occupational asbestos exposures contribute an increasing proportion of disease. With the exception of the United States, incidence continues to increase. In developed countries peak incidence is expected to occur before 2030. PMID:23977542

  16. [Diagnosis of malignant thyroid tumors by indirect thyroid lymphography].

    PubMed

    Serpukhovitin, S Iu; Bukhman, A I; Kazeev, K N; Tochilin, A V

    1985-01-01

    Indirect thyroidolymphography was used for 38 patients with malignant thyroid tumors. A conclusion has been made that indirect lymphography of the thyroid is a simple and rather informative diagnostic method for malignant thyroid tumors and should be followed by spot biopsy. PMID:2997774

  17. ONCOGENOMICS Genomic profiling of malignant melanoma using tiling-resolution

    E-print Network

    Ringnér, Markus

    ONCOGENOMICS Genomic profiling of malignant melanoma using tiling-resolution arrayCGH G Jo¨ nsson1, Lund, Sweden Malignant melanoma is an aggressive, heterogeneous disease where new biomarkers pathogenesis using 47 different melanoma cell lines and tiling-resolution bacter- ial artificial chromosome

  18. Ribavirin for Chronic Hepatitis Prevention among Patients with Hematologic Malignancies

    PubMed Central

    Tavitian, Suzanne; Peron, Jean-Marie; Huguet, Françoise; Kamar, Nassim; Abravanel, Florence; Beyne-Rauzy, Odile; Oberic, Lucie; Faguer, Stanislas; Alric, Laurent; Roussel, Murielle; Gaudin, Clément; Ysebaert, Loïc; Huynh, Anne

    2015-01-01

    Findings among a cohort of 26 patients who had hematologic malignancies and hepatitis E virus (HEV) infection support that HEV can induce chronic hepatitis. However, a 3-month course of ribavirin can induce a rapid viral clearance, reducing the risk for chronic hepatitis and enabling continuation of cytotoxic treatments for underlying malignancies. PMID:26197210

  19. Metastatic Malignant Melanoma in an alpaca (Vicugna pacos)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Malignant melanoma in a 7-year old, intact male alpaca with a chronic, non-healing wound on the left nares, weight loss and inappetance is described. Malignant melanoma was diagnosed in punch biopsy specimens from a mass on the maxilla associated with the non-healing wound and from a mass in the su...

  20. Risk factors for malignant transformation of mature cystic teratoma

    PubMed Central

    Park, Chan-Hong; Jung, Min-Hyung

    2015-01-01

    Objective The aim of this study was to investigate the preoperative characteristics of benign mature cystic teratoma (MCT) and struma ovarii and their risk factors associated malignancies, and determine the appropriate treatment options for these tumors. Methods This was a retrospective study on 248 patients who were pathologically diagnosed with ovarian MCT, struma ovarii, or malignant transformations of these tumors at Inje University Haeundae Paik Hospital from March 2010 to January 2015. Routinely evaluated results of adnexal masses before surgery were compared. Results A total of six patients (2.4%) were confirmed to have malignant tumors. Of the struma ovarii patients, two out of five patients (40%) were confirmed to have malignancy. The mean age at the diagnosis of patients with malignant transformation of teratomas was 43.0 years (range, 27 to 67 years), which was higher than that of patients with benign teratomas (36.5 years). The mean diameter of the tumor before surgery in the malignant tumor group was 11.4 cm and larger than 6.5 cm of benign group (P=0.003). The mean CA-125 level in the malignant tumor group was higher than that in the benign tumor group (P=0.01). Conclusion Risk factors for malignant transformation of MCT include elevated CA-125 levels, older age, large tumor masses, and postmenopausal status. PMID:26623411

  1. Meningioma after contralateral hemispherectomy for malignant glioma: case report.

    PubMed Central

    Wilson, P J; Ashley, D J

    1975-01-01

    A patient is described who successfully underwent cerebral hemispherectomy for malignant glioma and whose death nine months later, wrongly ascribed to recurrent malignancy, was in fact due to a subsequently-developing benign meningioma in the remaining hemisphere. The possible advantages of a modification of standard hemispherectomy technique are also discussed. Images PMID:1151416

  2. Brain metastasis of a malignant fibrous histiocytoma of the lung.

    PubMed

    Rosemberg, S; Delmonte, V; Nitrini, R; Caramelli, P

    1993-01-01

    Sarcomas metastatic to the brain as well as primary malignant fibrous histiocytomas of the lung are very unusual tumors. The authors report a case of a 52-year-old man who presented with neurological symptoms due to cerebral metastasis of a malignant fibrous histiocytoma of the lung and provide a review of the literature on the subject. PMID:8382575

  3. Five markers useful for the distinction of canine mammary malignancy

    PubMed Central

    2013-01-01

    Background Spontaneous canine mammary tumors constitute a serious clinical problem. There are significant differences in survival between cases with different tumor grades. Unfortunately, the distinction between various grades is not clear. A major problem in evaluating canine mammary cancer is identifying those, that are “truly” malignant. That is why the aim of our study was to find the new markers of canine malignancy, which could help to diagnose the most malignant tumors. Results Analysis of gene expression profiles of canine mammary carcinoma of various grade of malignancy followed by the boosted tree analysis distinguished a `gene set`. The expression of this gene set (sehrl, zfp37, mipep, relaxin, and magi3) differs significantly in the most malignant tumors at mRNA level as well as at protein level. Despite this `gene set` is very interesting as an additional tool to estimate canine mammary malignancy, it should be validated using higher number of samples. Conclusions The proposed gene set can constitute a `malignancy marker` that could help to distinguish the most malignant canine mammary carcinomas. These genes are also interesting as targets for further investigations and therapy. So far, only two of them were linked with the cancer development. PMID:23844591

  4. The gallium scan in malignant fibrous histiocytoma

    SciTech Connect

    Yeh, S.D.J.; Rosen, G.; Benua, R.S.

    1984-01-01

    Soft tissue sarcoma is a relatively uncommon malignancy. Of its various histological types, malignant fibrous histiocytoma is most common and usually is seen in late adult life affecting primarily extremities and trunk with or without bony involvement. Before undertaking potentially toxic treatments with chemotherapeutic agents, tumor aggressiveness must be estimated. The authors use /sup 67/Ga citrate to supplement other imaging modalities to measure size, location and extent prior to and during treatment. In all, 22 consecutive patients were studied, with 13 males and 9 females. The median age was 43 (range 15 to 68) with majority of patients in 4th to 6th decades. Extremity lesions were present in 18, pelvic in 1, thoracic in 2, and abdominal in 1. Eighteen patients were studied shortly after the diagnosis and 4 during their recurrences. In the 18 patients with primary tumor, 12 showed marked increased uptake in the region of tumor, or increased uptake in soft tissues with a distribution different from the changes noted in the MDP bone scan. In 4 patients with extremity lesions, abnormalities were seen in Ga but were not definite in MDP bone scans. Four patients had tumor recurrences following surgery, radiation therapy or chemotherapy. High Ga uptake was found in the regions of recurrent tumor in 2 and in the lung metastases of another. Interval changes were more easily appreciated in the Ga scan than in the MDP bone scan. Information obtained from Ga images provides additional clues in determining extent of soft tissue involvement and assists in monitoring therapeutic responses.

  5. Neurotrophins and B-cell malignancies.

    PubMed

    Hillis, Jennifer; O'Dwyer, Michael; Gorman, Adrienne M

    2016-01-01

    Neurotrophins and their receptors act as important proliferative and pro-survival factors in a variety of cell types. Neurotrophins are produced by multiple cell types in both pro- and mature forms, and can act in an autocrine or paracrine fashion. The p75(NTR) and Trk receptors can elicit signalling in response to the presence or absence of their corresponding neurotrophin ligands. This signalling, along with neurotrophin and receptor expression, varies between different cell types. Neurotrophins and their receptors have been shown to be expressed by and elicit signalling in B lymphocytes. In general, most neurotrophins are expressed by activated B-cells and memory B-cells. Likewise, the TrkB95 receptor is seen on activated B-cells, while TrkA and p75(NTR) are expressed by both resting and active B-cells as well as memory B-cells. Nerve growth factor stimulates B-cell proliferation, memory B-cell survival, antibody production and CD40 expression. Brain-derived neurotrophic factor is involved in B-cell maturation in the bone marrow through TrkB95. Overall neurotrophins and their receptors have been shown to be involved in B-cell proliferation, development, differentiation, antibody secretion and survival. As well as expression and activity in healthy B-cells, the neurotrophins and their receptors can contribute to B-cell malignancies including acute lymphoblastic leukaemia, diffuse large B-cell lymphoma, Burkitt's lymphoma and multiple myeloma. They are involved in B-cell malignancy survival and potentially in drug resistance. PMID:26399960

  6. Thyroid Malignancies in Survivors of Hodgkin Lymphoma

    SciTech Connect

    Michaelson, Evan M.; Chen, Yu-Hui; Silver, Barbara; Tishler, Roy B.; Marcus, Karen J.; Stevenson, Mary Ann; Ng, Andrea K.

    2014-03-01

    Purpose: To quantify the incidence of thyroid cancer after Hodgkin lymphoma (HL) and determine disease characteristics, risk factors, and treatment outcomes. Methods and Materials: Thyroid cancer cases were retrospectively identified from a multi-institutional database of 1981 HL patients treated between 1969 and 2008. Thyroid cancer risk factors were evaluated by a Poisson regression model. Results: With a median follow-up duration of 14.3 years (range, 0-41.2 years), 28 patients (1.4%) developed a thyroid malignancy. The overall incidence rate (expressed as the number of cases per 10,000 person-years) and 10-year cumulative incidence of thyroid cancer were 9.6 and 0.26%, respectively. There were no observed cases of thyroid malignancy in patients who received neck irradiation for HL after age 35 years. Age <20 years at HL diagnosis and female sex were significantly associated with thyroid cancer. The incidence rates of females aged <20 at HL diagnosis in the first 10 years, ?10 years, ?15 years, and ?20 years after treatment were 5, 31, 61, and 75 cases per 10,000 person-years of follow-up, respectively. At a median follow-up of 3.5 years after the thyroid cancer diagnosis, 26 patients (93%) were alive without disease, 1 (4%) was alive with metastatic disease, and 1 (4%) died of metastatic disease, at 6 and 3.6 years after the thyroid cancer diagnosis, respectively. Conclusions: Although HL survivors have an increased risk for thyroid cancer, the overall incidence is low. Routine thyroid cancer screening may benefit females treated at a young age and ?10 years from HL treatment owing to their higher risk, which increases over time.

  7. GLO1 Overexpression in Human Malignant Melanoma

    PubMed Central

    Bair, Warner B; Cabello, Christopher M; Uchida, Koji; Bause, Alexandra S; Wondrak, Georg T

    2010-01-01

    Glyoxalase I [lactoylglutathione lyase (EC 4.4.1.5) encoded by GLO1] is a ubiquitous cellular defense enzyme involved in the detoxification of methylglyoxal, a cytotoxic byproduct of glycolysis. Accumulative evidence suggests an important role of GLO1 expression in protection against methylglyoxal-dependent protein adduction and cellular damage associated with diabetes, cancer, and chronological aging. Based on the hypothesis that GLO1 upregulation may play a functional role in glycolytic adaptations of cancer cells, we examined GLO1 expression status in human melanoma tissue. Quantitative RT-PCR analysis of a cDNA tissue array containing 40 human melanoma tissues (stages III and IV) and 13 healthy controls revealed pronounced upregulation of GLO1 expression at the mRNA level. Immunohistochemical analysis of a melanoma tissue microarray confirmed upregulation of glyoxalase 1 protein levels in malignant melanoma tissue versus healthy human skin. Consistent with an essential role of GLO1 in melanoma cell defense against methylglyoxal cytotoxicity, siRNA interference targeting GLO1-expression (siGLO1) sensitized A375 and G361 human metastatic melanoma cells towards the antiproliferative, apoptogenic, and oxidative stress-inducing activity of exogenous methylglyoxal. Protein adduction by methylglyoxal was increased in siGLO1-transfected cells as revealed by immunodetection using a monoclonal antibody directed against the major methylglyoxal-derived epitope argpyrimidine that detected a single band of methylglyoxal-adducted protein in human LOX, G361, and A375 total cell lysates. Using 2D-proteomics followed by mass spectrometry the methylglyoxal-adducted protein was identified as heat shock protein 27 (Hsp27; HSPB1). Taken together, our data suggest a function of GLO1 in the regulation of detoxification and target-adduction by the glycolytic byproduct methylglyoxal in malignant melanoma. PMID:20093988

  8. Targeting Cyclooxygenase-2 in Hematological Malignancies: Rationale and Promise

    PubMed Central

    Bernard, M. P.; Bancos, S.; Sime, P. J.; Phipps, R. P.

    2009-01-01

    There is much interest in the potential use of Cox-2 selective inhibitors in combination with other cancer therapeutics. Malignancies of hematopoietic and non-hematopoietic origin often have increased expression of cyclooxygenase-2 (Cox-2), a key modulator of inflammation. For example, hematological malignancies such as chronic lymphocytic leukemia, chronic myeloid leukemia, Hodgkin’s lymphoma, non-Hodgkin’s lymphoma and multiple myeloma often highly express Cox-2, which correlates with poor patient prognosis. Expression of Cox-2 enhances survival and proliferation of malignant cells, while negatively influencing anti-tumor immunity. Hematological malignancies expressing elevated levels of Cox-2 potentially avoid immune responses by producing factors that enhance angiogenesis and metastases. Cellular immune responses regulated by natural killer cells, cytotoxic T lymphocytes, and T regulatory cells are also influenced by Cox-2 expression. Therefore, Cox-2 selective inhibitors have promising therapeutic potential in patients suffering from certain hematological malignancies. PMID:18691115

  9. Malignant transformation of diploid human fibroblasts by transfection of oncogenes

    SciTech Connect

    McCormick, J.J.

    1992-01-01

    This document consist of brief reports prepared by postdoctoral students supported by the project, each describing his accomplishments under the grant. Topics include (1) Malignant Transformation of MSU-1. 1 Cells by Gamma Radiation, (2) Correlation between Levels of ras Expression and Presence of Transformed Phenotypes Including Tumorigenicity, Using a Modulatable Promoter, (3) Relation between Specific rad Oncogene Expression, (4) Correlation of Genetic Changes in Fibroblastic Tumors with Malignancies, (5)Transformation of MSU-1.1 Cells by sis Oncogene, (6) Malignant Transformation of MSU-1.0 Cells, (7) Correlation of Urokinase Plasminogen Activation (mu-PA) with Malignant Phenotype, (8)Two Dimensional Gel Electrophoresis Studies of the Proteins of the Major Cell Strains of the MSU-1 Family of Cells, and (9) Correlation between Proteinase Activity Levels and Malignancy.

  10. Identification of new alternative splice events in the TCIRG1 gene in different human tissues

    SciTech Connect

    Smirnova, Anna S.; Morgun, Andrey . E-mail: anemorgun@hotmail.com; Shulzhenko, Natalia; Silva, Ismael D.C.G.; Gerbase-DeLima, Maria

    2005-05-13

    Two transcript variants (TV) of the T cell immune regulator gene 1 (TCIRG1) have already been characterized. TV1 encodes a subunit of the osteoclast vacuolar proton pump and TV2 encodes a T cell inhibitory receptor. Based on the search in dbEST, we validated by RT-PCR six new alternative splice events in TCIRG1 in most of the 28 human tissues studied. In addition, we observed that transcripts using the TV1 transcription start site and two splice forms previously described in a patient with infantile malignant osteopetrosis are also expressed in various tissues of healthy individuals. Studies of these nine splice forms in cytoplasmic RNA of peripheral blood mononuclear cells showed that at least six of them could be efficiently exported from the nucleus. Since various products with nearly ubiquitous tissue distribution are generated from TCIRG1, this gene may be involved in other processes besides immune response and bone resorption.

  11. Pigmented Pre-malignant and Malignant Lesions of Skin with Special Reference to Atypical Presentations

    PubMed Central

    Jindal, Rashmi; Singh, Sneha; Harsh, Meena; Ahmad, Sohaib

    2015-01-01

    Background Cutaneous melanocytic proliferations are diverse both morphologically as well as in their behavioural patterns. Both dermatologists and pathologists regularly encounter diagnostic dilemmas while interpreting such lesions. Aim To study all cutaneous premalignant and malignant lesions with respect to their clinical features and histopathological findings. Materials and Methods A retrospective study was done in the Department of Pathology over a period of 10 years (2004-14) on all the clinically pigmented lesions that were biopsied or excised. Out of these only premalignant and malignant melanocytic lesions were analysed with respect to their important clinical and histologic features. Immunohistochemistry was carried out using HMB-45 and S-100 where indicated. Results A total of 338 skin cancers were reported, out of these 27, 7.9% were cutaneous malignant melanoma. Premalignant lesions were 33. The mean age for premalignant lesions and melanomas was 43 years and 50.7 years respectively with a male predominance in both groups. The sole of foot/ankle was the most common site of involvement by melanoma (n=8,29.6%) while sun exposed sites like face and scalp were common sites for development of premalignant lesions like dysplastic nevi, lentigo simplex, pigmented seborrheic keratosis and Bowens disease. One case presented as post-traumatic scar tissue which turned out to be desmoplastic melanoma. One case of amelanotic melanoma presented as recurrent painful penile ulcers. Both cases were confirmed on Immunohistochemistry. Conclusion All pigmented lesions should be regarded as tumours of uncertain malignant potential and treated with complete excision if possible with long term follow up. PMID:26393132

  12. Infantile spasms and 15q11.2q13.1 chromosome duplication in two successive generations.

    PubMed

    Riikonen, Raili Sylvia; Wallden, Tiina; Kokkonen, Hannaleena

    2016-01-01

    Familial cases of West syndrome have been reported only in Japan. In that study no chromosomal analyses were made. It has been suggested that microarray analysis should be included in the diagnostic evaluation of patients with infantile spasms and developmental delay, when an evaluation for structural brain lesions and metabolic disorders reveal no abnormal findings. We report here the first case of infantile spasms and 15q11.2q13.1 chromosome duplication in two successive generations. The daughter and mother with infantile spasms, and the autistic son had the duplication. The clinical course of infantile spasms was very similar in the mother and daughter. The spasms were primarily considered to be of unknown aetiology. Chromosomal microarray analysis revealed a 6.2 Mb size 15q11.2q13.1 duplication. The duplication belongs to the 15q11q13 duplication syndrome (OMIM 608636) which when maternally derived is characterised by neuro-behavioural disorders like autism, hypotonia, cognitive deficit, language delay and epilepsy. The proportion of patients with unknown aetiology for infantile spasms will decrease when more careful chromosomal studies are made. Our report expands the phenotype of chromosome 15q duplication syndrome and is the first report of this abnormality in two successive generations of infantile spasms. PMID:26685108

  13. Malignant cancer and invasive placentation: A case for positive pleiotropy between endometrial and malignancy phenotypes.

    PubMed

    D'Souza, Alaric W; Wagner, Günter P

    2014-01-01

    Cancer metastasis is an invasive process that involves the transplantation of cells into new environments. Since human placentation is also invasive, hypotheses about a relationship between invasive placentation in eutherian mammals and metastasis have been proposed. The relationship between metastatic cancer and invasive placentation is usually presented in terms of antagonistic pleiotropy. According to this hypothesis, evolution of invasive placentation also established the mechanisms for cancer metastasis. Here, in contrast, we argue that the secondary evolution of less invasive placentation in some mammalian lineages may have resulted in positive pleiotropic effects on cancer survival by lowering malignancy rates. These positive pleiotropic effects would manifest themselves as resistance to cancer cell invasion. To provide a preliminary test of this proposal, we re-analyze data from Priester and Mantel (Occurrence of tumors in domestic animals. Data from 12 United States and Canadian colleges of veterinary medicine. J Natl Cancer Inst 1971; 47: :1333-44) about malignancy rates in cows, horses, cats and dogs. From our analysis we found that equines and bovines, animals with less invasive placentation, have lower rates of metastatic cancer than felines and canines in skin and glandular epithelial cancers as well as connective tissue sarcomas. We conclude that a link between type of placentation and species-specific malignancy rates is more likely related to derived mechanisms that suppress invasion rather than different degrees of fetal placental aggressiveness. PMID:25324490

  14. Detection of type IV collagenase activity in malignant ascites

    PubMed Central

    Sun, Xiao-Min; Dong, Wei-Guo; Yu, Bao-Ping; Luo, He-Sheng; Yu, Jie-Ping

    2003-01-01

    AIM: Type IV collagenase participates in invasion and metastasis of cancer cells. Malignant ascites is a manifestation of advanced malignant disease that is associated with invasion and metastasis of the peritoneal cavity. Thus, it is reasonable to hypothesize that type IV collagenase is linked to malignant ascites. The purpose of our study was to detect type IV collagenase activity in malignant ascites so as to provide the scientific basis for clinic diagnosis and treatment of malignant ascites. METHODS: Cirrhotic ascites (n = 36), tuberculous ascites (n = 8) and malignant ascites (n = 23) from patients with gastric cancer (n = 6), colon cancer (n = 5), ovarian cancer (n = 8) and other cancers (n = 4), including 2 hepatocellular cancers, 1 pancreatic cancer, 1 primary peritoneal carcinoma were collected by paracentesis. The ascites were made cell-free by centrifugation and stored frozen at -70 °C before determination. Type IV collagenase activity was determined by gelatin zymography. RESULTS: The activity of matrix metalloproteinases-2 and -9 could not be detected in ascites of hepatic cirrhosis and tuberculous peritonitis but could be detected in 20 and 18 out of 23 malignant ascites respectively. The positive rate of type IV collagenase (MMP-2, 87.0% and MMP-9, 78.3%) was higher than that by routine ascites tests (P < 0.01) in malignant ascites. Furthermore, the activity of MMP-2 was higher than that of MMP-9 (P = 0.022 < 0.05). CONCLUSION: Type IV collagenase is positive in malignant ascites. Detection of type IV collagenase activity is useful in qualitative diagnosis of ascites. Type IV collagenase may play an important role in malignant ascites formation. PMID:14606104

  15. More Complete Removal of Malignant Brain Tumors by Fluorescence-Guided Surgery

    ClinicalTrials.gov

    2015-10-30

    Benign Neoplasms, Brain; Brain Cancer; Brain Neoplasms, Benign; Brain Neoplasms, Malignant; Brain Tumor, Primary; Brain Tumor, Recurrent; Brain Tumors; Intracranial Neoplasms; Neoplasms, Brain; Neoplasms, Intracranial; Primary Brain Neoplasms; Primary Malignant Brain Neoplasms; Primary Malignant Brain Tumors; Gliomas; Glioblastoma

  16. Neonatal estradiol stimulation prevents epilepsy in Arx model of X-linked infantile spasms syndrome.

    PubMed

    Olivetti, Pedro R; Maheshwari, Atul; Noebels, Jeffrey L

    2014-01-22

    Infantile spasms are a catastrophic form of pediatric epilepsy with inadequate treatment. In patients, mutation of ARX, a transcription factor selectively expressed in neuronal precursors and adult inhibitory interneurons, impairs cell migration and causes a major inherited subtype of the disease X-linked infantile spasms syndrome. Using an animal model, the Arx((GCG)10+7) mouse, we determined that brief estradiol (E2) administration during early postnatal development prevented spasms in infancy and seizures in adult mutants. E2 was ineffective when delivered after puberty or 30 days after birth. Early E2 treatment altered mRNA levels of three downstream targets of Arx (Shox2, Ebf3, and Lgi1) and restored depleted interneuron populations without increasing GABAergic synaptic density. Postnatal E2 treatment may induce lasting transcriptional changes that lead to enduring disease modification and could potentially serve as a therapy for inherited interneuronopathies. PMID:24452264

  17. Interneuron, interrupted: molecular pathogenesis of ARX mutations and X-linked infantile spasms.

    PubMed

    Olivetti, Pedro R; Noebels, Jeffrey L

    2012-10-01

    X-linked Infantile Spasms Syndrome (ISSX) is a catastrophic epilepsy of early childhood with intractable seizures, intellectual disability, and poor prognosis. A spectrum of mutations in the Aristaless-Related Homeobox gene (ARX) has been linked to ISSX, and downstream targets of this interneuron-expressed transcription factor are being defined. Recent advances combining in vitro and in vivo methods have unveiled complex interactions between Arx and its binding partners and their effects on cell migration and maturation that can help explain the diversity of ARX phenotypes. New mutant mouse models of Arx-induced pathology, including a recent human triplet-repeat expansion mutation with a phenotype of infantile spasms and electrographic seizures, provide valuable tools for exploring the pathophysiology of Arx and substrates for testing novel therapies. PMID:22565167

  18. Clinical profile of vigabatrin as monotherapy for treatment of infantile spasms

    PubMed Central

    Lerner, Jason T; Salamon, Noriko; Sankar, Raman

    2010-01-01

    Vigabatrin, the first therapeutic agent to be approved by the Food and Drug Administration for the treatment of infantile spasms, as well as for adjunctive use in the treatment of refractory complex partial epilepsy, represents an important advance for patients with difficult-to-manage epilepsy. This review summarizes the complex history, chemistry, and pharmacology, as well as the clinical data leading to the approval of vigabatrin for infantile spasms in the US. The long path to its approval reflects the visual system and white matter toxicity concerns with this agent. This review provides a brief description of these concerns, and the regulatory safety monitoring and mitigation systems that have been put in place to enhance benefit over risk. PMID:21127692

  19. Interneuron, Interrupted: Molecular Pathogenesis of ARX Mutations and X-linked Infantile Spasms

    PubMed Central

    Olivetti, Pedro R.; Noebels, Jeffrey L.

    2012-01-01

    X-linked Infantile Spasms Syndrome (ISSX) is a catastrophic epilepsy of early childhood with intractable seizures, intellectual disability, and poor prognosis. A spectrum of mutations in the Aristaless-Related Homeobox gene (ARX) has been linked to ISSX, and downstream targets of this interneuron-expressed transcription factor are being defined. Recent advances combining in vitro and in vivo methods have unveiled complex interactions between Arx and its binding partners and their effects on cell migration and maturation that can help explain the diversity of ARX phenotypes. New mutant mouse models of Arx-induced pathology, including a recent human triplet-repeat expansion mutation with a phenotype of infantile spasms and electrographic seizures, provide valuable tools for exploring the pathophysiology of Arx and substrates for testing novel therapies. PMID:22565167

  20. Neonatal Estradiol Stimulation Prevents Epilepsy in Arx Model of X-Linked Infantile Spasms Syndrome

    PubMed Central

    Olivetti, Pedro R.; Maheshwari, Atul; Noebels, Jeffrey L.

    2014-01-01

    Infantile spasms are a catastrophic form of pediatric epilepsy with inadequate treatment. In patients, mutation of ARX, a transcription factor selectively expressed in neuronal precursors and adult inhibitory interneurons, impairs cell migration and causes a major inherited subtype of the disease X-linked infantile spasms syndrome. Using an animal model, the Arx(GCG)10+7 mouse, we determined that brief estradiol (E2) administration during early postnatal development prevented spasms in infancy and seizures in adult mutants. E2 was ineffective when delivered after puberty or 30 days after birth. Early E2 treatment altered mRNA levels of three downstream targets of Arx (Shox2, Ebf3, and Lgi1) and restored depleted interneuron populations without increasing GABAergic synaptic density. Postnatal E2 treatment may induce lasting transcriptional changes that lead to enduring disease modification and could potentially serve as a therapy for inherited interneuronopathies. PMID:24452264

  1. A myofibroblastic tumor. Infantile digital fibroma (recurrent digital fibrous tumor of childhood).

    PubMed Central

    Bhawan, J.; Bacchetta, C.; Joris, I.; Majno, G.

    1979-01-01

    Infantile digital fibromas are distinctive tumors both clinically and morphologically. A unique light microscopic features in the presence of intracytoplasmic, spherical, eosinophilic inclusion bodies. Previous electron microscopic studies have shown these bodies to consist of fibrils; bundles of fibrils have also been described in the cytoplasm. We have examined one such tumor, confirmed earlier findings, and established that the component cells are typical myofibroblasts. The latter are a variety of fibroblasts first described in granulation tissue; they are endowed with contractile properties and are characterized ultrastructurally by bundles of fibrils containing "dense bodies" such as are found in smooth muscle cells. Since our case is identical to those previously described, we propose that this tumor be called infantile digital myofibroblastoma. Images Figure 6 Figure 7 Figure 5 Figure 9 Figure 10 Figure 8 Figure 4 Figure 11 Figure 2 Figure 3 Figure 11 Figure 12 Figure 13 Figure 14 PMID:216266

  2. [Management of infantile cataracts: surgical technics and choices in lens implantation].

    PubMed

    Thouvenin, D

    2011-03-01

    Management of congenital or infantile cataracts benefited from progresses realized in adult surgery. It stays however specific to children's eyes and is incorporated in a global therapeutic strategy. It must be guided by a pediatric ophthalmogical team used to this kind of treatment. We report here, function of the type of cataract, uni or bilateral, congenital or infantile, the choice of the timing of surgery, of the therapeutic strategy, parental information, and preoperative evaluation. The actual standard of surgery is bimanual phacoaspiration with posterior capsulorhexis and anterior vitrectomy. It is described step by step. Indication of lens implantation, choice of the type and power of IOL function of age of the child is described, be it for initial or secondary lens implantation. PMID:21392844

  3. Osteomyelitis of Maxilla in Infantile With Periorbital Cellulitis: A Case Report.

    PubMed

    Feng, Zhiqiang; Chen, Xufeng; Cao, Fengdi; Lai, Renfa; Lin, Qiang

    2015-10-01

    Infantile osteomyelitis (IO) is an uncommon and life-threatening disease that can be misdiagnosed. Early diagnosis and treatment can reduce the incidence of sequel.In this case report, we present a 25-day-old male infant with apparent edema in the entire left periorbital region. Intraorally, the edema occurred in the mucosa of the upper left alveolar region, and 2 draining fistulas with exuded yellow-white pus were present in the left alveolar region. The patient received constant monitoring after admission, and was diagnosed as IO of the maxilla with periorbital cellulitis and sepsis. He also received incision and drainage and anti-inflammatory treatment. After discharge, the patient was followed up for 3 months by phone call, but no recurrence of symptoms was found.Infantile osteomyelitis is rare in clinic. This case report reminds us of the significance of IO and provides some implications on its diagnosis and treatment. PMID:26448016

  4. Clinicopathologic Findings of Hematological Malignancy: a Retrospective Autopsy Study.

    PubMed

    Dierksen, Jennifer; Buja, L Maximilian; Chen, Lei

    2015-09-01

    Hematological malignancies exhibit many clinical presentations, from ambiguous systemic symptoms to rapid multi-organ failure. By identifying common clinical, laboratory, and autopsy findings in patients with a hematological malignancy, living patients may be diagnosed and treated earlier. We retrospectively reviewed our institution's 2003-2013 autopsy and respective medical records for patients with a hematological malignancy. Clinical, laboratory and autopsy findings were retrieved. 30 patients with hematological malignancy were identified, including 14 "new" cases, defined here as diagnosed either post-mortem (n=6) or within 4 weeks of death (n=8). 16 patients had a known prior diagnosis of greater than 4 weeks and/or received treatment. "New" patients most frequently presented with pain, dyspnea and gastrointestinal symptoms. Common laboratory findings for new lymphoma patients included elevated aspartate aminotransferase, prothrombin time (PT), lactate dehydrogenase (LDH), lactic acidosis, and cytopenia. New leukemia patients had peripheral smear findings, thrombocytopenia, elevated PT, lactic acidosis and elevated LDH. Patients with a prior diagnosis of hematological malignancy had similar findings to new patients with increased thrombocytopenia in prior lymphoma cases. Immediate causes of death were most frequently multi-organ failure through malignant organ infiltration and/or septic shock. With an increased awareness of hematological malignancy in a differential diagnosis, a timely diagnosis or clinical interventions can eventually save lives. PMID:26586710

  5. Differentially Expressed Proteins in Malignant and Benign Adrenocortical Tumors

    PubMed Central

    Kjellin, Hanna; Johansson, Henrik; Höög, Anders; Lehtiö, Janne

    2014-01-01

    We have compared the microsomal protein composition of eight malignant and six benign adrenocortical tumors with proteomic methods. IGF2 had increased level in the malignant tumors, confirming previous microarray studies on the same material. Aldolase A, a glycolytic enzyme, also showed increased levels in the malignant tissue compared to the benign. Additionally, several proteins belonging to complex I in the mitochondrial respiration chain showed decreased levels in the malignant tissue. Taken together, this may indicate a shift in energy metabolism where glycolysis may be favored over tight coupling of glycolysis and mitochondrial respiration, a phenomenon known as the Warburg effect. One of the complex I proteins that showed decreased levels in the malignant tissue was GRIM-19. This protein has been suggested as a tumor suppressive protein by being a negative regulator of STAT3. In summary, an analysis of the microsomal proteome in adrenocortical tumors identifies groups of proteins as well as specific proteins differentially expressed in the benign and malignant forms. These proteins shed light on the biology behind malignancy and could delineate future drug targets. PMID:24498411

  6. SCN2A mutation is associated with infantile spasms and bitemporal glucose hypometabolism

    PubMed Central

    Sundaram, Senthil K; Chugani, Harry T; Tiwari, Vijay N; Huq, AHM M

    2013-01-01

    BACKGROUND Genetic mutations play crucial role in the etiology of cryptogenic infantile spasms but the cause is still unknown in a significant proportion of patients. Whole exome sequencing technology shows great promise in identifying genetic causes of infantile spasms. METHODS We performed whole exome sequencing and 2-deoxy-2-(18F)fluoro-D-glucose positron emission tomography scan of a male child with infantile spasms. Exome sequencing was also performed in parents to identify any de novo mutations. RESULTS The positron emission tomography scan showed a pattern of bilateral symmetric temporal lobe glucose hypometabolism. A total of 8171 non-synonymous variants were identified in the child. Despite the large number of nonsynonymous variants, there was only a single de novo missense mutation in SCN2A in the child (NCBI hg19 assembly, position: Chr2:166234116, K1422E). Subsequent Sanger sequencing confirmed the de novo status of this variant. This mutation has never been reported in 6500 individuals of the exome variant server database. Similarly, this variant is not reported in online mendelian inheritance in man database or human gene mutation database. It has previously been shown that SCN2A mutations are associated with hippocampal hyperexcitability. Therefore, we speculate that IS and bitemporal hypometabolism in our patient might have been caused by hippocampal hyperexcitability due to SCN2A mutation. CONCLUSIONS The simultaneous presence of an SCN2A mutation and bitemporal hypometabolism in this patient with infantile spasms suggests a plausible hippocampal origin. However, additional mechanistic and clinical studies are required to validate this link. PMID:23827426

  7. Vigabatrin therapy implicates neocortical high frequency oscillations in an animal model of infantile spasms.

    PubMed

    Frost, James D; Le, John T; Lee, Chong L; Ballester-Rosado, Carlos; Hrachovy, Richard A; Swann, John W

    2015-10-01

    Abnormal high frequency oscillations (HFOs) in EEG recordings are thought to be reflections of mechanisms responsible for focal seizure generation in the temporal lobe and neocortex. HFOs have also been recorded in patients and animal models of infantile spasms. If HFOs are important contributors to infantile spasms then anticonvulsant drugs that suppress these seizures should decrease the occurrence of HFOs. In experiments reported here, we used long-term video/EEG recordings with digital sampling rates capable of capturing HFOs. We tested the effectiveness of vigabatrin (VGB) in the TTX animal model of infantile spasms. VGB was found to be quite effective in suppressing spasms. In 3 of 5 animals, spasms ceased after a daily two week treatment. In the other 2 rats, spasm frequency dramatically decreased but gradually increased following treatment cessation. In all animals, hypsarrhythmia was abolished by the last treatment day. As VGB suppressed the frequency of spasms, there was a decrease in the intensity of the behavioral spasms and the duration of the ictal EEG event. Analysis showed that there was a burst of high frequency activity at ictal onset, followed by a later burst of HFOs. VGB was found to selectively suppress the late HFOs of ictal complexes. VGB also suppressed abnormal HFOs recorded during the interictal periods. Thus VGB was found to be effective in suppressing both the generation of spasms and hypsarrhythmia in the TTX model. Vigabatrin also appears to preferentially suppress the generation of abnormal HFOs, thus implicating neocortical HFOs in the infantile spasms disease state. PMID:26026423

  8. Teaching neuroimages: infant with glutaric aciduria type 1 presenting with infantile spasms and hypsarrhythmia.

    PubMed

    Young-Lin, Nichole; Shalev, Sarah; Glenn, Orit A; Gardner, Marisa; Lee, Chung; Wynshaw-Boris, Anthony; Gelfand, Amy A

    2013-12-10

    A 7-month-old boy with glutaric aciduria type 1 (GA1) presented with 1 week of clustered flexor spasms. Examination revealed mild axial hypotonia without encephalopathy. Video-EEG monitoring revealed hypsarrhythmia and infantile spasms (figure, A). MRI showed acute basal ganglia injury (figure, B). After 3 weeks of prednisolone treatment, 5-month follow-up showed continued resolution of hypsarrhythmia and spasms. PMID:24323445

  9. Substrate reduction therapy in the infantile form of Tay-Sachs disease.

    PubMed

    Bembi, B; Marchetti, F; Guerci, V I; Ciana, G; Addobbati, R; Grasso, D; Barone, R; Cariati, R; Fernandez-Guillen, L; Butters, T; Pittis, M G

    2006-01-24

    Substrate reduction therapy (SRT) with miglustat has been proposed for treatment of some lysosomal storage disorders. Based on the positive experience in Gaucher disease and experimental data in Tay-Sachs (TSD) and Sandhoff animal models, the authors investigated the clinical efficacy of SRT in two patients with infantile TSD. SRT could not arrest the patients' neurologic deterioration. However, a significant drug concentration in CSF as well as macrocephaly prevention were observed. PMID:16434676

  10. Noninvasive imaging of oral premalignancy and malignancy

    NASA Astrophysics Data System (ADS)

    Wilder-Smith, Petra; Krasieva, T.; Jung, W.; You, J. S.; Chen, Z.; Osann, K.; Tromberg, B.

    2005-04-01

    Objectives: Early detection of cancer and its curable precursors remains the best way to ensure patient survival and quality of life. Despite significant advances in treatment, oral cancer still results in 10,000 U.S. deaths annually, mainly due to the late detection of most oral lesions. Specific aim was to use a combination of non-invasive optical in vivo technologies to test a multi-modality approach to non-invasive diagnostics of oral premalignancy and malignancy. Methods: In the hamster cheek pouch model (120 hamsters), in vivo optical coherence tomography (OCT) and optical Doppler tomography (ODT) mapped epithelial, subepithelial and vascular change throughout carcinogenesis in specific, marked sites. In vivo multi-wavelength multi-photon (MPM) and second harmonic generated (SHG) fluorescence techniques provided parallel data on surface and subsurface tissue structure, specifically collagen presence and structure, cellular presence, and vasculature. Images were diagnosed by 2 blinded, pre-standardized investigators using a standardized scale from 0-6 for all modalities. After sacrifice, histopathological sections were prepared and pathology evaluated on a scale of 0-6. ANOVA techniques compared imaging diagnostics with histopathology. 95% confidence limits of the sensitivity and specificity were established for the diagnostic capability of OCT/ODT+ MPM/SHG using ROC curves and kappa statistics. Results: Imaging data were reproducibly obtained with good accuracy. Carcinogenesis-related structural and vascular changes were clearly visible to tissue depths of 2mm. Sensitivity (OCT/ODT alone: 71-88%; OCT+MPM/SHG: 79-91%) and specificity (OCT alone: 62-83%;OCT+MPM/SHG: 67-90%) compared well with conventional techniques. Conclusions: OCT/ODT and MPM/SHG are promising non-invasive in vivo diagnostic modalities for oral dysplasia and malignancy. Supported by CRFA 30003, CCRP 00-01391V-20235, NIH (LAMMP) RR01192, DOE DE903-91ER 61227, NIH EB-00293 CA91717, NSF BES-86924, AFOSR FA 9550-04-1-0101.

  11. Treatment of infantile spasms with very high dose prednisolone before high dose ACTH

    PubMed Central

    Hussain, Shaun A.; Shinnar, Shlomo; Kwong, Grace; Lerner, Jason T.; Matsumoto, Joyce H.; Wu, Joyce Y.; Shields, W. Donald; Sankar, Raman

    2013-01-01

    Summary Objective This study investigated the short-term response to a standardized hormonal therapy protocol for treatment of infantile spasms. Methods Twenty-seven children with video-EEG confirmed infantile spasms received very high dose (8 mg/kg/day, max 60 mg/day) oral prednisolone for 2 weeks. Response (absence of both hypsarrhythmia and spasms) to prednisolone was ascertained by repeat overnight video-EEG. Responders were tapered off over 2 weeks and non-responders were immediately transitioned to high dose (150 IU/m2/day) intramuscular ACTH for 2 additional weeks. Response was again determined by overnight video-EEG after ACTH therapy. Results Sixty-three percent (17/27) of patients responded completely to prednisolone. Subsequently, 40% (4/10) of prednisolone non-responders exhibited a complete response after an additional 2-week course with ACTH. Among 27 subjects with median follow-up of 13.5 months (interquartile range 4.8-25.9), 12% (2/17) of prednisolone responders and 50% (2/4) of ACTH responders experienced a relapse between 2 and 9 months after initial response. Significance Very high dose prednisolone demonstrated significantly higher efficacy than previously reported for lower doses in prior studies. High dose ACTH may be superior to very high dose prednisolone, and in lieu of a definitive clinical trial, the choice between prednisolone and ACTH for initial treatment of infantile spasms remains controversial. PMID:24446954

  12. Reduced Grating Acuity Associated with Retinal Toxicity in Children with Infantile Spasms on Vigabatrin Therapy

    PubMed Central

    Durbin, Sivan; Mirabella, Giuseppe; Buncic, J. Raymond; Westall, Carol A.

    2013-01-01

    Purpose To determine whether visual functions are decreased in children with infantile spasms and vigabatrin-attributed retinal toxicity. Methods Contrast sensitivity and grating acuity were measured by using sweep visual evoked potential (VEP) testing in 42 children with infantile spasms (mean age, 29.23 ± 18.31 months). All children had been exposed to vigabatrin (VGB) for a minimum of 1 month. These children were divided into retinal toxicity and no toxicity groupings based on 30-Hz flicker amplitude reductions on the full-field electroretinogram. A multivariate analysis of variance (MANOVA) compared visual functions between children with and without retinal toxicity. Results The MANOVA showed that visual function was significantly affected by VGB retinal toxicity. Further univariate analysis revealed that grating acuity was significantly reduced in children with toxicity. No differences in contrast sensitivity were found between children with toxicity and those without. Conclusions Reduced visual functions from VGB-attributed retinal toxicity can be detected in children with infantile spasms with the sweep VEP. PMID:19279311

  13. Clinicopathological study of three cases of infantile fibromatosis of the orbit.

    PubMed

    Hayashi, Kengo; Katori, Nobutada; Otsuki, Yoshiro; Ohno-Matsui, Kyoko

    2014-10-01

    We report the clinical and pathological findings in three infants with infantile fibromatosis that involved several extraocular muscles which led to disorders of ocular motility. We also describe their clinical features before and after surgery. This was a retrospective interventional case study with clinicopathological correlations. We present three cases of infantile fibromatosis that were diagnosed by clinical features and histopathlogical examination of biopsy specimens. The three patients were all female children aged 1, 3, and 3 years at their initial visit. The orbital tumor was unilateral in all patients. All three patients had disorders of ocular motility because the tumors involved ?2 extraocular muscles. The margins between the tumor and the involved extraocular muscles were not distinct. We performed partial resection of the tumors to preserve the extraocular muscles. In all cases, the tumors partially remained, but periodic postoperative magnetic resonance imaging showed no enlargement of the tumors during the follow-up period. All three patients had residual limitations of eye movements. We should consider the postoperative binocular function when we treat infantile benign fibrous tumors involving the extraocular muscles. PMID:24535563

  14. Autism spectrum disorders in children with a history of infantile spasms: a population-based study.

    PubMed

    Saemundsen, Evald; Ludvigsson, Petur; Rafnsson, Vilhjalmur

    2007-09-01

    The objective of this article is to describe autistic spectrum disorders in children diagnosed with infantile spasms in the first year of life. The source of data was the records of all 3 pediatric departments in Iceland. Twenty children born between 1981 and 1998 who had infantile spasms were invited to participate. When appropriate, the parents of these children were asked to complete the Social Communication Questionnaire. Children scoring 10 points or higher on the questionnaire were selected for further examination using the Autism Diagnostic Interview- Revised and either the Autism Diagnostic Observation Schedule or the Childhood Autism Rating Scale. All participants were given appropriate cognitive tests or measures of adaptive behavior. The parents of 17 children (10 boys, 7 girls) agreed to participate in the study. Age at assessment ranged from 5 to 19 years with a mean age of 11 years and 6 months. Fourteen children had at least one neurodevelopmental disorder. Six (6/17), or 35.3%, were diagnosed with autism spectrum disorder (3 boys, 3 girls), five of these had a history of symptomatic infantile spasms, and four were profoundly mentally retarded (IQ/DQ<20). If the diagnosis of autism spectrum disorder was restricted to children with a developmental age of 24 months or more (3 cases), the prevalence was 17.6%. The estimates found in this study exceed the estimated prevalence of autism spectrum disorder in the general population. PMID:17890408

  15. Hypomethylation of DNA from Benign and Malignant Human Colon Neoplasms

    NASA Astrophysics Data System (ADS)

    Goelz, Susan E.; Vogelstein, Bert; Hamilton, Stanley R.; Feinberg, Andrew P.

    1985-04-01

    The methylation state of DNA from human colon tissue displaying neoplastic growth was determined by means of restriction endonuclease analysis. When compared to DNA from adjacent normal tissue, DNA from both benign colon polyps and malignant carcinomas was substantially hypomethylated. With the use of probes for growth hormone, ? -globin, ? -chorionic gonadotropin, and ? -crystallin, methylation changes were detected in all 23 neoplastic growths examined. Benign polyps were hypomethylated to a degree similar to that in malignant tissue. These results indicate that hypomethylation is a consistent biochemical characteristic of human colonic tumors and is an alteration in the DNA that precedes malignancy.

  16. Nuclear factor kappa B role in inflammation associated gastrointestinal malignancies

    PubMed Central

    Gambhir, Sahil; Vyas, Dinesh; Hollis, Michael; Aekka, Apporva; Vyas, Arpita

    2015-01-01

    Nuclear factor kappa B (NF-?B) has an established role in the regulation of innate immunity and inflammation. NF-?B is also involved in critical mechanisms connecting inflammation and cancer development. Recent investigations suggest that the NF-?B signaling cascade may be the central mediator of gastrointestinal malignancies including esophageal, gastric and colorectal cancers. This review will explore NF-?B’s function in inflammation-associated gastrointestinal malignancies, highlighting its oncogenic contribution to each step of carcinogenesis. NF-?B’s role in the inflammation-to-carcinoma sequence in gastrointestinal malignancies warrants stronger emphasis upon targeting this pathway in achieving greater therapeutic efficacy. PMID:25805923

  17. Malignant peripheral nerve sheath tumor of proximal third tibia.

    PubMed

    Rao, Arunkumar; Ingle, Sachin B; Rajurkar, Pawan; Goyal, Vishav; Dokrimare, Nikhil

    2015-10-10

    A 16-year-old man had aswelling over the anterior aspect of the proximal third of the tibia for 1 year, which was peanut size initially and progressively increased to its present size of 10 cm × 8 cm. He underwent fine needle aspiration cytology (FNAC) twice during this period and reported aspindle cell sarcoma. Malignant peripheral nerve sheath tumor (MPNST) is a malignancy of the connective tissue surrounding the nerves. Previously, MPNST was also known as neurofibrosarcoma, malignant schwannoma, andneurogenic sarcoma. We are reporting this case for its rarity and peculiar mode of presentation. FNAC/core biopsy can be used as an effective tool to achievethe correct pathological diagnosis. PMID:26468455

  18. Radiation-induced malignant and atypical peripheral nerve sheath tumors

    SciTech Connect

    Foley, K.M.; Woodruff, J.M.; Ellis, F.T.; Posner, J.B.

    1980-04-01

    The reported peripheral nerve complications of therapeutic irradiation in humans include brachial and lumbar plexus fibrosis and cranial and peripheral nerve atrophy. We have encountered 9 patients with malignant (7) and atypical (2) peripheral nerve tumors occurring in an irradiated site suggesting that such tumors represent another delayed effect of radiation treatment on peripheral nerve. In all instances the radio-theray was within an acceptable radiation dosage, yet 3 patients developed local radiation-induced skin and bony abnormalities. The malignant peripheral nerve sheath tumors developed only in the radiation port. Animal studies support the clinical observation that malignant peripheral nerve sheath tumors can occur as a delayed effect of irradiation.

  19. Assessment of Musculoskeletal Malignancies with Functional MR Imaging.

    PubMed

    Vilanova, Joan C; Baleato-Gonzalez, Sandra; Romero, Maria José; Carrascoso-Arranz, Javier; Luna, Antonio

    2016-02-01

    Functional MR imaging is the technique of choice to evaluate and manage malignant musculoskeletal masses. Advanced MR imaging sequences include chemical shift MR imaging, diffusion-weighted imaging with apparent diffusion coefficient mapping, MR spectroscopy imaging, and dynamic contrast-enhanced perfusion imaging. Functional MR imaging adds value to morphologic sequences in the detection, characterization, staging, and posttherapy assessment of malignant musculoskeletal malignancies. This article reviews the technical role of each functional sequence and their clinical applications to allow more confident decisions to be made. Multiparametric analysis of functional and anatomic MR sequences allows musculoskeletal tumors analysis to be improved. PMID:26613884

  20. Diagnostic Imaging of Malignant Tumors in the Orofacial Region.

    PubMed

    Singer, Steven R; Creanga, Adriana G

    2016-01-01

    Though rare, malignancies of the orofacial region often have serious consequences. Malignancies of the orofacial region are typically discovered during a clinical examination or from a patient complaint. Initial discovery from a radiograph is rare. Three-dimensional imaging using advanced imaging techniques often provides adequate information about the aggressive nature of a lesion. Radiographically based imaging demonstrates mainly hard-tissue destruction and, rarely, bone deposition. MRI provides excellent visualization of soft-tissue densities without using ionizing radiation. Functional imaging is used to visualize increased metabolic activity associated with malignancies, and is excellent for determining the metastatic spread of a lesion. PMID:26614953

  1. Isolated production of aldosterone by a malignant adrenal carcinoma.

    PubMed Central

    Levine, D. S.; Fischer, D. G.; Forman, B. H.

    1984-01-01

    A 45-year-old female developed hypertension and hypokalemia. Elevated plasma aldosterone and suppressed plasma renin levels were measured with no evidence for glucocorticoid or androgen abnormalities. A left adrenal tumor was removed that showed histologic criteria for malignancy. It is commonly taught that malignant adrenal tumors are recognized by their multiple hormone production. However, isolated aldosterone production by a carcinoma can occur and requires close follow-up observation and therapy for this highly malignant tumor. Images FIG. 1 FIG. 2 FIG. 3 FIG. 4 FIG. 5 PMID:6537692

  2. Malignant peripheral nerve sheath tumor of proximal third tibia

    PubMed Central

    Rao, Arunkumar; Ingle, Sachin B; Rajurkar, Pawan; Goyal, Vishav; Dokrimare, Nikhil

    2015-01-01

    A 16-year-old man had aswelling over the anterior aspect of the proximal third of the tibia for 1 year, which was peanut size initially and progressively increased to its present size of 10 cm × 8 cm. He underwent fine needle aspiration cytology (FNAC) twice during this period and reported aspindle cell sarcoma. Malignant peripheral nerve sheath tumor (MPNST) is a malignancy of the connective tissue surrounding the nerves. Previously, MPNST was also known as neurofibrosarcoma, malignant schwannoma, andneurogenic sarcoma. We are reporting this case for its rarity and peculiar mode of presentation. FNAC/core biopsy can be used as an effective tool to achievethe correct pathological diagnosis. PMID:26468455

  3. Somatic SETBP1 mutations in myeloid malignancies.

    PubMed

    Makishima, Hideki; Yoshida, Kenichi; Nguyen, Nhu; Przychodzen, Bartlomiej; Sanada, Masashi; Okuno, Yusuke; Ng, Kwok Peng; Gudmundsson, Kristbjorn O; Vishwakarma, Bandana A; Jerez, Andres; Gomez-Segui, Ines; Takahashi, Mariko; Shiraishi, Yuichi; Nagata, Yasunobu; Guinta, Kathryn; Mori, Hiraku; Sekeres, Mikkael A; Chiba, Kenichi; Tanaka, Hiroko; Muramatsu, Hideki; Sakaguchi, Hirotoshi; Paquette, Ronald L; McDevitt, Michael A; Kojima, Seiji; Saunthararajah, Yogen; Miyano, Satoru; Shih, Lee-Yung; Du, Yang; Ogawa, Seishi; Maciejewski, Jaroslaw P

    2013-08-01

    Here we report whole-exome sequencing of individuals with various myeloid malignancies and identify recurrent somatic mutations in SETBP1, consistent with a recent report on atypical chronic myeloid leukemia (aCML). Closely positioned somatic SETBP1 mutations encoding changes in Asp868, Ser869, Gly870, Ile871 and Asp880, which match germline mutations in Schinzel-Giedion syndrome (SGS), were detected in 17% of secondary acute myeloid leukemias (sAML) and 15% of chronic myelomonocytic leukemia (CMML) cases. These results from deep sequencing demonstrate a higher mutational detection rate than reported with conventional sequencing methodology. Mutant cases were associated with advanced age and monosomy 7/deletion 7q (-7/del(7q)) constituting poor prognostic factors. Analysis of serially collected samples indicated that SETBP1 mutations were acquired during leukemic evolution. Transduction with mutant Setbp1 led to the immortalization of mouse myeloid progenitors that showed enhanced proliferative capacity compared to cells transduced with wild-type Setbp1. Somatic mutations of SETBP1 seem to cause gain of function, are associated with myeloid leukemic transformation and convey poor prognosis in myelodysplastic syndromes (MDS) and CMML. PMID:23832012

  4. [Pelvic actinomycosis simulating adnexal malignant tumor].

    PubMed

    Benkiran, L; Gamra, L; Lamalmi, N; Essouyeh, M; Regragui, A; Amrani, M; Souadka, A; Melabbas, M A

    2002-01-01

    The purpose of this report is to describe the case of a 35-year-old patient admitted to the National Oncology Institute in Rabat, Morocco for pelvic pain and deteriorating general status ongoing for 8 months. Clinical and ultrasonographic examination showed a heterogenous mass measuring 7 cm in maximum width located inferior and lateral to the inferior aspect of the right side of the uterus. These findings were suggestive of a malignant tumor of the right ovary. Ovariectomy and omentectomy were performed. Histological examination of surgical specimens demonstrated right tubo-ovarian actinomycosis associated with peritonitis. Genital tract actinomycosis is an uncommon finding in women of childbearing age. It is due to colonization by a pyogenic bacteria (Actinomyces) usually secondary to a gastrointestinal infection, e.g. ileocecum, and sometimes in association with the presence of an intrauterine device or foreign body. Based on this case report, the authors discuss abdominopelvic actinomyocosis with emphasis on tumor-like findings that can lead to misdiagnosis by clinicians and radiologists. PMID:12038184

  5. Mast cells mediate malignant pleural effusion formation.

    PubMed

    Giannou, Anastasios D; Marazioti, Antonia; Spella, Magda; Kanellakis, Nikolaos I; Apostolopoulou, Hara; Psallidas, Ioannis; Prijovich, Zeljko M; Vreka, Malamati; Zazara, Dimitra E; Lilis, Ioannis; Papaleonidopoulos, Vassilios; Kairi, Chrysoula A; Patmanidi, Alexandra L; Giopanou, Ioanna; Spiropoulou, Nikolitsa; Harokopos, Vaggelis; Aidinis, Vassilis; Spyratos, Dionisios; Teliousi, Stamatia; Papadaki, Helen; Taraviras, Stavros; Snyder, Linda A; Eickelberg, Oliver; Kardamakis, Dimitrios; Iwakura, Yoichiro; Feyerabend, Thorsten B; Rodewald, Hans-Reimer; Kalomenidis, Ioannis; Blackwell, Timothy S; Agalioti, Theodora; Stathopoulos, Georgios T

    2015-06-01

    Mast cells (MCs) have been identified in various tumors; however, the role of these cells in tumorigenesis remains controversial. Here, we quantified MCs in human and murine malignant pleural effusions (MPEs) and evaluated the fate and function of these cells in MPE development. Evaluation of murine MPE-competent lung and colon adenocarcinomas revealed that these tumors actively attract and subsequently degranulate MCs in the pleural space by elaborating CCL2 and osteopontin. MCs were required for effusion development, as MPEs did not form in mice lacking MCs, and pleural infusion of MCs with MPE-incompetent cells promoted MPE formation. Once homed to the pleural space, MCs released tryptase AB1 and IL-1?, which in turn induced pleural vasculature leakiness and triggered NF-?B activation in pleural tumor cells, thereby fostering pleural fluid accumulation and tumor growth. Evaluation of human effusions revealed that MCs are elevated in MPEs compared with benign effusions. Moreover, MC abundance correlated with MPE formation in a human cancer cell-induced effusion model. Treatment of mice with the c-KIT inhibitor imatinib mesylate limited effusion precipitation by mouse and human adenocarcinoma cells. Together, the results of this study indicate that MCs are required for MPE formation and suggest that MC-dependent effusion formation is therapeutically addressable. PMID:25915587

  6. PTEN: Multiple Functions in Human Malignant Tumors

    PubMed Central

    Milella, Michele; Falcone, Italia; Conciatori, Fabiana; Cesta Incani, Ursula; Del Curatolo, Anais; Inzerilli, Nicola; Nuzzo, Carmen M. A.; Vaccaro, Vanja; Vari, Sabrina; Cognetti, Francesco; Ciuffreda, Ludovica

    2015-01-01

    PTEN is the most important negative regulator of the PI3K signaling pathway. In addition to its canonical, PI3K inhibition-dependent functions, PTEN can also function as a tumor suppressor in a PI3K-independent manner. Indeed, the PTEN network regulates a broad spectrum of biological functions, modulating the flow of information from membrane-bound growth factor receptors to nuclear transcription factors, occurring in concert with other tumor suppressors and oncogenic signaling pathways. PTEN acts through its lipid and protein phosphatase activity and other non-enzymatic mechanisms. Studies conducted over the past 10?years have expanded our understanding of the biological role of PTEN, showing that in addition to its ability to regulate proliferation and cell survival, it also plays an intriguing role in regulating genomic stability, cell migration, stem cell self-renewal, and tumor microenvironment. Changes in PTEN protein levels, location, and enzymatic activity through various molecular mechanisms can generate a continuum of functional PTEN levels in inherited syndromes, sporadic cancers, and other diseases. PTEN activity can indeed, be modulated by mutations, epigenetic silencing, transcriptional repression, aberrant protein localization, and post-translational modifications. This review will discuss our current understanding of the biological role of PTEN, how PTEN expression and activity are regulated, and the consequences of PTEN dysregulation in human malignant tumors. PMID:25763354

  7. Malignant melanoma at a scientific laboratory

    SciTech Connect

    Shy, C.M.; Checkoway, H.; Marshall, E.G.

    1985-11-15

    The general consensus of the seven reviewers is that occupational exposures at Lawrence Livermore National Laboratory have not been established as a causal factor for the observed excess of malignant melanoma. Several observations support the impression that some or all of the observed melanoma excess may be attributable to intense surveillance and enhanced detection of early stage melanoma lesions. Since the incidence of melanomas among Laboratory employees has not diminished, an early harvesting effect is unlikely. This suggests the distinct possibility that localized, in situ melanomas that would normally not be detected are being reported, and that in the absence of this enhanced detection, many of these early stage lesions would show little or no clinical progression. This phenomenon would explain the continued high incidence of melanomas in the absence of a physical or chemical inciting cause. A key point in this reasoning is the issue of the rate of growth of early stage melanomas, and this point remains a key question for study. Even if the observed excess cannot be explained by detection bias, the reviewers agree that the Austin and Reynolds' study does not make a convincing case for occupational factors being a cause of the high melanoma incidence. 6 refs.

  8. Improved radioimmunotherapy of hematologic malignancies. [Final report

    SciTech Connect

    Press, O.W.

    1992-03-24

    This research project proposes to develop novel new approaches of improving the radioimmunodetection and radioimmunotherapy of malignancies by augmenting retention of radioimmunoconjugates by tumor cells. The approaches shown to be effective in these laboratory experiments will subsequently be incorporated into out ongoing clinical trials in patients. Specific project objectives include: to study the rates of endocytosis, intracellular routing, and metabolic degradation of radiolabeled monoclonal antibodies targeting tumor-associated antigens on human leukemia and lymphoma cells; To examine the effects of lysosomotropic amines (e.g. chloroquine, amantadine), carboxylic ionophores (monensin, nigericin), and thioamides (propylthiouracil), on the retention of radiolabeled MoAbs by tumor cells; to examine the impact of newer radioiodination techniques (tyramine cellobiose, paraiodobenzoyl) on the metabolic degradation of radioiodinated antibodies; to compare the endocytosis, intracellular routing, and degradation of radioimmunoconjugates prepared with different radionuclides ({sup 131}Iodine, {sup 111}Indium, {sup 90}Yttrium, {sup 99m}Technetium, {sup 186}Rhenium); and to examine the utility of radioimmunoconjugates targeting oncogene products for the radioimmunotherapy and radioimmunoscintigraphy of cancer.

  9. Mast cells mediate malignant pleural effusion formation

    PubMed Central

    Giannou, Anastasios D.; Marazioti, Antonia; Spella, Magda; Kanellakis, Nikolaos I.; Apostolopoulou, Hara; Psallidas, Ioannis; Prijovich, Zeljko M.; Vreka, Malamati; Zazara, Dimitra E.; Lilis, Ioannis; Papaleonidopoulos, Vassilios; Kairi, Chrysoula A.; Patmanidi, Alexandra L.; Giopanou, Ioanna; Spiropoulou, Nikolitsa; Harokopos, Vaggelis; Aidinis, Vassilis; Spyratos, Dionisios; Teliousi, Stamatia; Papadaki, Helen; Taraviras, Stavros; Snyder, Linda A.; Eickelberg, Oliver; Kardamakis, Dimitrios; Iwakura, Yoichiro; Feyerabend, Thorsten B.; Rodewald, Hans-Reimer; Kalomenidis, Ioannis; Blackwell, Timothy S.; Agalioti, Theodora; Stathopoulos, Georgios T.

    2015-01-01

    Mast cells (MCs) have been identified in various tumors; however, the role of these cells in tumorigenesis remains controversial. Here, we quantified MCs in human and murine malignant pleural effusions (MPEs) and evaluated the fate and function of these cells in MPE development. Evaluation of murine MPE-competent lung and colon adenocarcinomas revealed that these tumors actively attract and subsequently degranulate MCs in the pleural space by elaborating CCL2 and osteopontin. MCs were required for effusion development, as MPEs did not form in mice lacking MCs, and pleural infusion of MCs with MPE-incompetent cells promoted MPE formation. Once homed to the pleural space, MCs released tryptase AB1 and IL-1?, which in turn induced pleural vasculature leakiness and triggered NF-?B activation in pleural tumor cells, thereby fostering pleural fluid accumulation and tumor growth. Evaluation of human effusions revealed that MCs are elevated in MPEs compared with benign effusions. Moreover, MC abundance correlated with MPE formation in a human cancer cell–induced effusion model. Treatment of mice with the c-KIT inhibitor imatinib mesylate limited effusion precipitation by mouse and human adenocarcinoma cells. Together, the results of this study indicate that MCs are required for MPE formation and suggest that MC-dependent effusion formation is therapeutically addressable. PMID:25915587

  10. Wavelengths effective in induction of malignant melanoma

    SciTech Connect

    Setlow, R.B.; Grist, E.; Thompson, K.; Woodhead, A.D. )

    1993-07-15

    It is generally agreed that sunlight exposure is one of the etiologic agents in malignant melanoma of fair-skinned individuals. However, the wavelengths responsible for tumorigenesis are not known, although DNA is assumed to be the target because individuals defective in the repair of UV damage to DNA are several thousandfold more prone to the disease than the average population. Heavily pigmented back-cross hybrids of the genus Xiphophorus (platyfish and swordtails) are very sensitive to melanoma induction by single exposures to UV. The authors irradiated groups of five 6-day-old fish with narrow wavelength bands at 302, 313, 365, 405, and 436 nm and score the irradiated animals for melanomas 4 months later. They used several exposures at each wavelength to obtain estimates of the sensitivity for melanoma induction as a function of exposure and wavelength. The action spectrum (sensitivity per incident photon as a function of wavelength) for melanoma induction shows appreciable sensitivity at 365, 405, and probably 436 nm, suggesting that wavelengths not absorbed directly in DNA are effective in induction. They interpret the results as indicating that light energy absorbed in melanin is effective in inducing melanomas in this animal model and that, in natural sunlight, 90-95% of melanoma induction may be attributed to wavelengths >320 nm-the UV-A and visible spectral regions. 25 refs., 4 figs., 1 tab.

  11. Extracolonic malignancies in inflammatory bowel disease.

    PubMed

    Ekbom, A; Helmick, C; Zack, M; Adami, H O

    1991-04-01

    A population-based cohort with inflammatory bowel disease consisting of 4776 patients (3121 with ulcerative colitis and 1655 with Crohn's disease) was followed for 1 to 50 years for the occurrence of malignant neoplasms. Two hundred eighty-three cancers were observed versus 189.1 expected (standardized incidence ratio [SIR] = 1.5, 95% confidence limits [CL] 1.3 to 1.7). One hundred seventy-eight extracolonic cancers were observed versus 168.8 expected (SIR = 1.1, 95% CL 0.9 to 1.2). In Crohn's disease and extensive ulcerative colitis, observed cases were close to those expected but in ulcerative proctitis, the relative risk of extracolonic cancers was close to significantly increased (SIR = 1.3, 95% CL 1.0 to 1.7). Squamous skin cancers after Crohn's disease (SIR = 5.5, 95% CL 2.0 to 11.9) and connective tissue cancers after ulcerative colitis (SIR = 4.0, 95% CL 1.0 to 10.2) were significantly increased. Those having extensive ulcerative colitis at diagnosis had an increased risk of brain cancers (SIR = 2.4, 95% CL 1.0 to 4.6). Patients with extensive ulcerative colitis had lower than expected risk of breast cancer (SIR = 0.4, 95% CL 0.1 to 1.0). PMID:2004319

  12. Wavelengths Effective in Induction of Malignant Melanoma

    NASA Astrophysics Data System (ADS)

    Setlow, Richard B.; Grist, Eleanor; Thompson, Keith; Woodhead, Avril D.

    1993-07-01

    It is generally agreed that sunlight exposure is one of the etiologic agents in malignant melanoma of fair-skinned individuals. However, the wavelengths responsible for tumorigenesis are not known, although DNA is assumed to be the target because individuals defective in the repair of UV damage to DNA are several thousandfold more prone to the disease than the average population. Heavily pigmented backcross hybrids of the genus Xiphophorus (platyfish and swordtails) are very sensitive to melanoma induction by single exposures to UV. We irradiated groups of five 6-day-old fish with narrow wavelength bands at 302, 313, 365, 405, and 436 nm and scored the irradiated animals for melanomas 4 months later. We used several exposures at each wavelength to obtain estimates of the sensitivity for melanoma induction as a function of exposure and wavelength. The action spectrum (sensitivity per incident photon as a function of wavelength) for melanoma induction shows appreciable sensitivity at 365, 405, and probably 436 nm, suggesting that wavelengths not absorbed directly in DNA are effective in induction. We interpret the results as indicating that light energy absorbed in melanin is effective in inducing melanomas in this animal model and that, in natural sunlight, 90-95% of melanoma induction may be attributed to wavelengths > 320 nm-the UV-A and visible spectral regions.

  13. Management of intestinal obstruction in advanced malignancy

    PubMed Central

    Ferguson, Henry John Murray; Ferguson, Claire Irene; Speakman, John; Ismail, Tariq

    2015-01-01

    Patients with incurable, advanced abdominal or pelvic malignancy often present to acute surgical departments with symptoms and signs of intestinal obstruction. It is rare for bowel strangulation to occur in these presentations, and spontaneous resolution often occurs, so the luxury of time should be afforded while decisions are made regarding surgery. Cross-sectional imaging is valuable in determining the underlying mechanism and pathology. The majority of these patients will not be suitable for an operation, and will be best managed in conjunction with a palliative medicine team. Surgeons require a good working knowledge of the mechanisms of action of anti-emetics, anti-secretories and analgesics to tailor early management to individual patients, while decisions regarding potential surgery are made. Deciding if and when to perform operative intervention in this group is complex, and fraught with both technical and emotional challenges. Surgery in this group is highly morbid, with no current evidence available concerning quality of life following surgery. The limited evidence concerning operative strategy suggests that resection and primary anastomosis results in improved survival, over bypass or stoma formation. Realistic prognostication and involvement of the patient, care-givers and the multidisciplinary team in treatment decisions is mandatory if optimum outcomes are to be achieved. PMID:26288731

  14. Malignant sweat gland tumours: an update.

    PubMed

    Cardoso, José C; Calonje, Eduardo

    2015-11-01

    Cutaneous adnexal tumours can be a diagnostic challenge for the pathologist. This is particularly true in the case of tumours with sweat gland differentiation, due to a large number of rare entities, a multiplicity of names to designate the same neoplasms and consequent lack of consensus regarding their classification and nomenclature. In the traditional view, sweat gland tumours were divided into eccrine and apocrine. However, this has been challenged in recent years, and in fact many of these tumours may have both eccrine and apocrine variants. Some display more complex features and defy classification, due to the presence of other lines of differentiation, namely follicular and/or sebaceous (in the case of apocrine tumours, due to the close embryological relationship between apocrine glands, hair follicles and sebaceous glands). The present paper reviews and updates the basic concepts regarding the following malignant sweat gland tumours: apocrine carcinoma, porocarcinoma, hidradenocarcinoma, spiradenocarcinoma, cylindrocarcinoma, microcystic adnexal carcinoma and related entities, squamoid eccrine ductal carcinoma, digital papillary adenocarcinoma, primary cutaneous mucinous carcinoma, endocrine mucin-producing sweat gland carcinoma and primary cutaneous signet ring cell carcinoma. Particular emphasis is put in recent findings that may have implications in the diagnosis and management of these tumours. PMID:26114606

  15. Particle Radiation Therapy for Gastrointestinal Malignancies

    PubMed Central

    Meyer, Jeffrey J.; Willett, Christopher G.

    2007-01-01

    Treatment-related toxicity is common in the radiotherapeutic management of cancers of the gastrointestinal tract. These toxicities can diminish treatment efficacy by necessitating treatment breaks, limiting the radiation dose that can be delivered, and hindering concomitant use of chemotherapy and targeted drug agents. Many efforts have focused on widening the gap between the likelihood of tumor control and the likelihood of toxicities associated with radiation. Use of particles that exhibit a Bragg peak phenomenon in their interactions with tissue, such as protons, heavier ions like carbon ions, and pions, is one means of concentrating radiation dose in tumors and away from normal tissues. Neutron beams have also been used in the treatment of gastrointestinal cancers in an effort to take advantage of their potent biologic effects. This report reviews basic particle radiation physics and biology, as well as the clinical experience with protons, heavier ions, pions, and neutrons in the treatment of various gastrointestinal malignancies. Potential future directions in clinical research with particle therapy are discussed. PMID:19360149

  16. Malignant histiocytosis. A phenotypic and genotypic investigation.

    PubMed Central

    Cattoretti, G.; Villa, A.; Vezzoni, P.; Giardini, R.; Lombardi, L.; Rilke, F.

    1990-01-01

    Ten cases of malignant histiocytosis (MH) were evaluated for clinical and histopathologic features, phenotype, and rearrangement of T cell receptor (TCR) beta, gamma, and alpha and immunoglobulin (Ig) genes (7/10). All cases were HLA-DR+ and CD30-positive. Four cases had molecular evidence of T cell lineage such as TCR beta, gamma, and alpha rearrangements, and one additional case synthesized the cytoplasmic TCR beta chain. The remaining five cases did not show unequivocal T, B, natural killer (NK) cell, or macrophagic origin, and three of them had germline TCR and Ig genes. Ultrastructural analysis was not helpful for the definition of the cell lineage. Most myelomonocytic markers (MAC387, CD13, CD14, CD64, CD68) were either negative on the MH cells or were expressed on cells with rearranged TCR gene. Precursor (CD34, CD7) and NK (CD16, CD56, and CD57) cell markers were not found. The lineage of a number of cases of MH remains unresolved. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 PMID:2349962

  17. Origins of heterogeneous ovarian carcinomas. A molecular cytogenetic analysis of histologically benign, low malignant potential, and fully malignant components.

    PubMed Central

    Wolf, N. G.; Abdul-Karim, F. W.; Schork, N. J.; Schwartz, S.

    1996-01-01

    It is unclear whether ovarian carcinomas develop from malignant transformation of benign precursors or whether they arise de novo. Thus, histologically benign or low malignant potential components found in heterogeneous ovarian carcinomas may be remnants of pre-existing lesions that progressed to malignancy or, alternatively, elements that arose independently (de novo). In a third possible interpretation, they represent areas of malignant epithelium that matured. We evaluated clonal relationships of histological components in 10 heterogeneous ovarian carcinomas using fluorescence in situ hybridization and confocal microscopy. Detailed analysis of aneuploidy for chromosomes 8, 12, and 17 on intact paraffin sections revealed that two tumors were aneuploid in all components, two lacked abnormalities in benign-appearing components, and one lacked aneuploidy in both histologically benign and low malignant potential components. Histological appearance was significantly related to aneuploidy (P < 0.05). The distribution of aneuploidy among tumor components strongly supports the tumor progression theory and demonstrates that the de novo hypothesis is highly unlikely (P < 0.001). Results also indicate that benign-appearing components in heterogeneous ovarian carcinomas do not represent maturation of malignant tissue and suggest that some benign tumors that become cancerous may have genetic aberrations that predispose them to malignant transformation. Images Figure 1 Figure 2 PMID:8701990

  18. Extratemporal Malignant Nerve Sheath Tumor of Facial Nerve with Coexistent Intratemporal Neurofibroma Mimicking Malignant Intratemporal Extension

    PubMed Central

    Nakahira, Mitsuhiko; Saito, Naoko; Sugasawa, Masashi

    2015-01-01

    We present an extremely unusual case of an extratemporal facial nerve malignant peripheral nerve sheath tumor (MPNST) arising from preexistent intratemporal neurofibroma, illustrating a difficulty in discriminating between perineural spread of the MPNST and the preexistent intratemporal neurofibroma on preoperative radiographic images. The most interesting point was that preoperative CT scan and MR images led to misinterpretation that MPNST extended proximally along the facial nerve canal. It is important to recognize that the intratemporal perineural spread of neurofibromas and MPNST share common imaging characteristics. This is the first report (to our knowledge) of these 2 lesions coexisting in the facial nerve, leading to misinterpretation on preoperative images. PMID:26347326

  19. CDKL5 mutations cause infantile spasms, early onset seizures, and severe mental retardation in female patients

    PubMed Central

    Archer, H L; Evans, J; Edwards, S; Colley, J; Newbury?Ecob, R; O'Callaghan, F; Huyton, M; O'Regan, M; Tolmie, J; Sampson, J; Clarke, A; Osborne, J

    2006-01-01

    Objective To determine the frequency of mutations in CDKL5 in both male and female patients with infantile spasms or early onset epilepsy of unknown cause, and to consider whether the breadth of the reported phenotype would be extended by studying a different patient group. Methods Two groups of patients were investigated for CDKL5 mutations. Group 1 comprised 73 patients (57 female, 16 male) referred to Cardiff for CDKL5 analysis, of whom 49 (42 female, 7 male) had epileptic seizure onset in the first six months of life. Group 2 comprised 26 patients (11 female, 15 male) with infantile spasms previously recruited to a clinical trial, the UK Infantile Spasms Study. Where a likely pathogenic mutation was identified, further clinical data were reviewed. Results Seven likely pathogenic mutations were found among female patients from group 1 with epileptic seizure onset in the first six months of life, accounting for seven of the 42 in this group (17%). No mutations other than the already published mutation were found in female patients from group 2, or in any male patient from either study group. All patients with mutations had early signs of developmental delay and most had made little developmental progress. Further clinical information was available for six patients: autistic features and tactile hypersensitivity were common but only one had suggestive Rett?like features. All had a severe epileptic seizure disorder, all but one of whom had myoclonic jerks. The EEG showed focal or generalised changes and in those with infantile spasms, hypsarrhythmia. Slow frequencies were seen frequently with a frontal or fronto?temporal predominance and high amplitudes. Conclusions The spectrum of the epileptic seizure disorder, and associated EEG changes, in those with CDKL5 mutations is broader than previously reported. CDKL5 mutations are a significant cause of infantile spasms and early epileptic seizures in female patients, and of a later intractable seizure disorder, irrespective of whether they have suspected Rett syndrome. Analysis should be considered in these patients in the clinical setting. PMID:16611748

  20. Retroperitoneal Malignant Peripheral Nerve Sheath Tumour: A Rare Case Report.

    PubMed

    Deger, Ayse Nur; Bayar, Mehmet Akif; Caydere, Muzaffer; Deger, Hakki; Tayfur, Mahir

    2015-09-01

    Malignant nerve sheath tumours (MPNST) are rare neoplasias and retroperitoneal cases are fairly rare and clinically difficult to be detected, but they are very agressive neoplasias. MPNST are frequently seen in head, neck and upper extremities. In patients with NF1; MPNST, a poor-prognostic lesion, may result from a malignant degeneration of a former plexiform neurofibroma. It is necessary to be aware of a potential malignancy in patients diagnosed with plexiform neurofibroma. We present a 21-year-old female with a diagnosis of MPNST. The patient was admited to the hospital because of a tumour in the subcutaneous region on her left buttock. The surgeon's clinical diagnosis was lipoma. After the pathological examination of biopsy specimen, the lesion was identified as "plexiform neurofibroma" and then the patient was diagnosed with Neurofibromatosis Type 1 (NF1). Simultaneously, another mass on the retroperitoneal region was identified as malignant peripheral nerve sheath tumour (MPNST). PMID:26500915

  1. Retroperitoneal Malignant Peripheral Nerve Sheath Tumour: A Rare Case Report

    PubMed Central

    Bayar, Mehmet Akif; Caydere, Muzaffer; Deger, Hakki; Tayfur, Mahir

    2015-01-01

    Malignant nerve sheath tumours (MPNST) are rare neoplasias and retroperitoneal cases are fairly rare and clinically difficult to be detected, but they are very agressive neoplasias. MPNST are frequently seen in head, neck and upper extremities. In patients with NF1; MPNST, a poor-prognostic lesion, may result from a malignant degeneration of a former plexiform neurofibroma. It is necessary to be aware of a potential malignancy in patients diagnosed with plexiform neurofibroma. We present a 21-year-old female with a diagnosis of MPNST. The patient was admited to the hospital because of a tumour in the subcutaneous region on her left buttock. The surgeon’s clinical diagnosis was lipoma. After the pathological examination of biopsy specimen, the lesion was identified as “plexiform neurofibroma” and then the patient was diagnosed with Neurofibromatosis Type 1 (NF1). Simultaneously, another mass on the retroperitoneal region was identified as malignant peripheral nerve sheath tumour (MPNST). PMID:26500915

  2. Malignant Peripheral Nerve Sheath Tumour of the Maxilla

    PubMed Central

    Sahai, Puja; Mohanti, Bidhu Kalyan; Nath, Devajit; Bhasker, Suman; Chander, Subhash; Bakhshi, Sameer; Singh, Chirom Amit

    2014-01-01

    A 38-year-old man was diagnosed with malignant peripheral nerve sheath tumour of the maxilla. He was treated with total maxillectomy. Histopathological examination of the resected specimen revealed a close resection margin. The tumour was of high grade with an MIB-1 labelling index of almost 60%. At six weeks following the surgery, he developed local tumour relapse. The patient succumbed to the disease at five months from the time of diagnosis. The present report underlines the locally aggressive nature of malignant peripheral nerve sheath tumour of the maxilla which necessitates an early therapeutic intervention. A complete resection with clear margins is the most important prognostic factor for malignant peripheral nerve sheath tumour in the head and neck region. Adjuvant radiotherapy may be considered to improve the local control. Future research may demarcate the role of targeted therapy for patients with malignant peripheral nerve sheath tumour. PMID:24744936

  3. Malignant Mesothelioma Mimicking Invasive Mammary Carcinoma in a Male Breast

    PubMed Central

    Desouki, Mohamed Mokhtar; Long, Daniel Jerad

    2015-01-01

    Malignant mesothelioma is an uncommon tumor with strong association with asbestos exposure. Few cases of malignant pleural mesothelioma metastatic to the female breast have been reported. Herein, we presented, for the first time, a case of locally infiltrating malignant pleural mesothelioma forming a mass in the breast of a male as the first pathologically confirmed manifestation of the disease. Breast ultrasound revealed an irregular mass in the right breast which involves the pectoralis muscle. Breast core biopsy revealed a proliferation of neoplastic epithelioid cells mimicking an infiltrating pleomorphic lobular carcinoma. IHC studies showed the cells to be positive for calretinin, CK5/6, WT1, and CK7. The cells were negative for MOC-31, BerEp4, ER, and PR. A final diagnosis of malignant mesothelioma, epithelioid type, was rendered. This case demonstrates the importance of considering a broad differential diagnosis in the setting of atypical presentation with application of a panel of IHC markers. PMID:26448888

  4. PDT for malignant tumors: a clinical analysis of 152 cases

    NASA Astrophysics Data System (ADS)

    Zhuang, Shi-Zhang; Wang, Yun-Zhen; Li, Xin; Zhang, Changjun; Wang, Jian-Zhao; Zhang, Da-Ren

    1993-03-01

    Hematoporphyrin derivative (HPD) laser photodynamic therapy (PDT) was applied for the patients of 152 cases of malignant tumors, including tumors of the lip, tongue, esophagus, urinary bladder, skin, larynx, vagina, etc. Since early 1981 good results have been obtained.

  5. MPH Malignant Brain Rules: Breeze Training Transcript: Mar 19 07

    Cancer.gov

    NATIONAL INSTITUTES OF HEALTH NATIONAL CANCER INSTITUTE SURVEILLANCE, EPIDEMIOLOGY AND END RESULTS (SEER) PROGRAM 2007 Multiple Primary and Histology Coding Rules Breeze Sessions Malignant Brain Rules March 19, 2007 SLIDE ONE Hello, everyone. This

  6. MPH Malignant Brain Practicum: Breeze Training Transcript: March 23 07

    Cancer.gov

    NATIONAL INSTITUTES OF HEALTH NATIONAL CANCER INSTITUTE SURVEILLANCE, EPIDEMIOLOGY AND END RESULTS (SEER) PROGRAM 2007 Multiple Primary and Histology Coding Rules Breeze Sessions Malignant Brain Practicum March 23, 2007 INTRODUCTION Welcome back.

  7. [Pathologic characteristics of malignant neoplasms occurring in the elderly].

    PubMed

    Arai, Tomio; Matsuda, Yoko; Aida, Junko; Takubo, Kaiyo

    2015-08-01

    Malignant neoplasm preferentially occurs in the elderly. Common cancers in the elderly are gastric, colorectal, lung and prostate cancers in men whereas colorectal, lung, gastric and pancreatic cancers in women. There are several characteristic features such as tumor location, histology, biological behavior and pathway of carcinogenesis in malignant neoplasms occurring in the elderly. Multiple cancers increase with aging. Although it is generally believed that carcinoma in the elderly shows well differentiation, slow growth, low incidence of metastasis and favorable prognosis, the tumor does not always show such features. Regarding biological behavior of malignant tumor in the elderly, age-related alterations of the host such as stromal weakness and decreased immune response against cancer cell invasion should be considered as well as characteristics of tumor cell itself. Thus, we need a specific strategy for treatment for malignant neoplasms in the elderly. PMID:26281698

  8. Primary malignant melanoma of the lung: a case report.

    PubMed

    Liu, Gao-Hua; Liu, Jun; Dong, Hui; Tang, Xiao-Jun

    2014-01-01

    Primary malignant melanoma of the lung is a very rare disease with about 40 cases reported in English literature. We report a 49-year-old female with history of 2 month chest pain who was revealed to have a peripheral lung mass in left upper lobe by chest CT scan. Left upper lobectomy was performed and post-operative pathology revealed to be primary malignant melanoma of the lung. 4 months after operation, a node in right breast was found by patient herself and needle aspiration biopsy revealed to be breast cancer. The patient refused any diagnostic and therapeutic procedure and died of extensive metastasis 3 months later. Primary malignant melanoma of the lung is highly malignant disease with poor prognosis in most patients. PMID:25126176

  9. Primary malignant melanoma of the lung: a case report

    PubMed Central

    Liu, Gao-Hua; Liu, Jun; Dong, Hui; Tang, Xiao-Jun

    2014-01-01

    Primary malignant melanoma of the lung is a very rare disease with about 40 cases reported in English literature. We report a 49-year-old female with history of 2 month chest pain who was revealed to have a peripheral lung mass in left upper lobe by chest CT scan. Left upper lobectomy was performed and post-operative pathology revealed to be primary malignant melanoma of the lung. 4 months after operation, a node in right breast was found by patient herself and needle aspiration biopsy revealed to be breast cancer. The patient refused any diagnostic and therapeutic procedure and died of extensive metastasis 3 months later. Primary malignant melanoma of the lung is highly malignant disease with poor prognosis in most patients. PMID:25126176

  10. Endogenous fluorescence of normal and malignant fibroblast cultures

    NASA Astrophysics Data System (ADS)

    Grossman, Nili; Chaims, Orna; Ilovitz, Efrat; Mark, Shlomo; Goppas, Jacob; Salman, Ahmad; Cohen, Beny; Mordechai, Shaul

    2000-11-01

    Light-induced Fluorescence (LIF) technique is based on fluorescence emitted from intracellular chromophores upon illumination of cells by monochromatic light. We compared LIF emitted from a pair of normal and malignant murine cell lines, differing in H-ras expression. The malignant cells fluoresced significantly less than the normal cells, upon excitation at 290 +/- 10 nm. For both cell types, fluorescence decreased with decreasing cell concentration, but at each concentration, the normal cells fluoresced more than the malignant cells. The effect of viability and metabolic stage of the cells on this pattern was compared. The difference among the cells was not due to a difference in protein or DNA content. Thus, this model system demonstrates the specific contribution of H-ras to sub-cellular chromophores, resulting in a significant difference in their autofluorescence intensity, while measuring both emission and excitation scans. This study suggests a potential use of the LIF technique to distinguish between normal and malignant cells and tissues.

  11. Imaging Features following Thermal Ablation of Lung Malignancies.

    PubMed

    Chheang, Sophie; Abtin, Feredoin; Guteirrez, Antonio; Genshaft, Scott; Suh, Robert

    2013-06-01

    Percutaneous image-guided thermal ablation is gaining attraction as an effective alternative to surgical resection for patients with primary and secondary malignancies of the lung. Currently, no standard follow-up imaging protocol has been established or uniformly accepted. The early identification of residual or recurrent tumor would in theory enable the practitioner to offer expeditious retreatment or alternative treatment. This review elaborates on the imaging findings following thermal ablation, both heat- and cold-based, of nonresectable pulmonary malignancies. PMID:24436532

  12. MRI of bone marrow abnormalities in hematological malignancies.

    PubMed

    Silva, Jose Roberto; Hayashi, Daichi; Yonenaga, Takenori; Fukuda, Kunihiko; Genant, Harry K; Lin, Chieh; Rahmouni, Alain; Guermazi, Ali

    2013-01-01

    Magnetic resonance imaging (MRI) is essential for evaluating bone marrow. Bone marrow undergoes constant modification and its appearance on MRI changes in response. Knowledge of the types of changes and their origins is essential for analysis of MRI findings of bone marrow infiltration with hematological malignancies. This pictorial review describes the MRI pulse sequences used for imaging of bone marrow, and illustrates bone marrow changes due hematological malignancies, including changes following treatment. PMID:23748035

  13. Benign and Malignant Male Breast Diseases: Radiologic and Pathologic Correlation.

    PubMed

    Yen, Peggy P W; Sinha, Namita; Barnes, Penny J; Butt, Robinette; Iles, Sian

    2015-08-01

    Male breast disease comprises a wide spectrum of benign and malignant processes. We present the spectrum of diseases encountered at our institution over the past 7 years (2007-2013) and correlate their radiological and histopathological appearances. Gynaecomastia is the most frequently encountered disease due to its association with a variety of causes. Male breast malignancies, though rare, must be considered. The most frequently encountered pathological characteristic is invasive and the predominant histologic subtypes are infiltrating ductal carcinomas. PMID:26073217

  14. Hematologic malignancies: at the forefront of immunotherapeutic innovation

    PubMed Central

    Bachireddy, Pavan; Burkhardt, Ute E.; Rajasagi, Mohini; Wu, Catherine J.

    2015-01-01

    The recent successes of cancer immunotherapy have stimulated interest for the potential widespread application of these approaches; hematologic malignancies have provided both initial proofs-of-concept and an informative testing ground for a variety of immune-based therapeutics. The immune-cell origin of many of the blood malignancies provides a unique opportunity to both understand the mechanisms of human immune-responsiveness and immune-evasion as well as to exploit the unique therapeutic opportunities they provide. PMID:25786696

  15. Histone deacetylase inhibitors and epigenetic regulation in lymphoid malignancies.

    PubMed

    Markozashvili, Diana; Ribrag, Vincent; Vassetzky, Yegor S

    2015-12-01

    A vast majority of lymphomas and leukaemias are results of translocations. These translocations produce various genetic and epigenetic changes that lead to oncogenesis. This opens an opportunity to use a relatively new class of anti-cancer agents, inhibitors of histone deacetylases (HDACi) to target lymphoid malignancies. Surprisingly, the rational basis for treatment of lymphomas with HDACi is far from clear, although some positive results have been obtained. Here we analyze the effect of histone deacetylase (HDAC) inhibitors on lymphoid malignancies. PMID:26423245

  16. Future Directions in Malignant Hyperthermia Research and Patient Care

    PubMed Central

    Hirshey Dirksen, Sharon J.; Larach, Marilyn Green; Rosenberg, Henry; Brandom, Barbara W.; Parness, Jerome; Lang, Robert Scott; Gangadharan, Meera; Pezalski, Tyler

    2011-01-01

    Malignant hyperthermia (MH) is a complex pharmacogenetic disorder of muscle metabolism. To more closely examine the complexities of MH and other related muscle disorders, the Malignant Hyperthermia Association of the United States recently sponsored a scientific conference at which an interdisciplinary group of experts gathered to share new information and ideas. In this Special Article, we highlight key concepts and theories presented at the conference along with exciting new trends and challenges in MH research and patient care. PMID:21709147

  17. Malignant Mesothelioma: Facts, Myths and Hypotheses

    PubMed Central

    Carbone, Michele; Ly, Bevan H.; Dodson, Ronald F.; Pagano, Ian; Morris, Paul T.; Dogan, Umran A.; Gazdar, Adi F.; Pass, Harvey I.; Yang, Haining

    2011-01-01

    Malignant mesothelioma (MM) is a neoplasm arising from mesothelial cells lining the pleural, peritoneal, and pericardial cavities. Over 20 million people in the US are at risk of developing MM due to asbestos exposure. MM mortality rates are estimated to increase by 5-10% per year in most industrialized countries until about 2020. The incidence of MM in men has continued to rise during the past 50 years, while the incidence in women appears largely unchanged. It is estimated that about 50-80% of pleural MM in men and 20-30% in women developed in individuals whose history indicates asbestos exposure(s) above that expected from most background settings. While rare for women, about 30% of peritoneal mesothelioma in men has been associated with exposure to asbestos. Erionite is a potent carcinogenic mineral fiber capable of causing both pleural and peritoneal MM. Since erionite is considerably less widespread than asbestos, the number of MM cases associated with erionite exposure is smaller. Asbestos induces DNA alterations mostly by inducing mesothelial cells and reactive macrophages to secrete mutagenic oxygen and nitrogen species. In addition, asbestos carcinogenesis is linked to the chronic inflammatory process caused by the deposition of a sufficient number of asbestos fibers and the consequent release of pro-inflammatory molecules, especially HMGB-1, the master switch that starts the inflammatory process, and TNF-alpha by macrophages and mesothelial cells. Genetic predisposition, radiation exposure and viral infection are co-factors that can alone or together with asbestos and erionite cause MM. PMID:21412769

  18. Inflammasome Modulation by Chemotherapeutics in Malignant Mesothelioma

    PubMed Central

    Westbom, Catherine; Thompson, Joyce K.; Leggett, Alan; MacPherson, Maximilian; Beuschel, Stacie; Pass, Harvey; Vacek, Pamela; Shukla, Arti

    2015-01-01

    Malignant mesothelioma (MM) is a fatal disease in dire need of therapy. The role of inflammasomes in cancer is not very well studied, however, literature supports both pro-and anti-tumorigenic effects of inflammasomes on cancer depending upon the type of cancer. Asbestos is a causative agent for MM and we have shown before that it causes inflammasome priming and activation in mesothelial cells. MM tumor cells/tissues showed decreased levels of inflammasome components like NLRP3 and caspase-1 as compared to human mesothelial cells or normal tissue counterpart of tumor. Based on our preliminary findings we hypothesized that treatment of MMs with chemotherapeutic drugs may elevate the levels of NLRP3 and caspase-1 resulting in increased cell death by pyroptosis while increasing the levels of IL-1? and other pro-inflammatory molecules. Therefore, a combined strategy of chemotherapeutic drug and IL-1R antagonist may play a beneficial role in MM therapy. To test our hypothesis we used two human MM tumor cell lines (Hmeso, H2373) and two chemotherapeutic drugs (doxorubicin, cisplatin). Through a series of experiments we showed that both chemotherapeutic drugs caused increases in NLRP3 levels, caspase-1 activation, pyroptosis and pro-inflammatory molecules released from MM cells. In vivo studies using SCID mice and Hmeso cells showed that tumors were smaller in combined treatment group of cisplatin and IL-1R antagonist (Anakinra) as compared to cisplatin alone or untreated control groups. Taken together our study suggests that chemotherapeutic drugs in combination with IL-1R antagonist may have a beneficial role in MM treatment. PMID:26689911

  19. [Malignant catarrhal fever in zoo ruminants].

    PubMed

    Hänichen, T; Reid, H W; Wiesner, H; Hermanns, W

    1998-09-01

    An outbreak of malignant catarrhal fever (MCF) in Indian gauer (Bos gaurus gaurus) and Javan banteng (Bos javanicus javanicus) occurred in the year 1964 and killed almost all animals of the groups of these species kept at the Munich zoo at that time. In the consecutive years at highly irregular intervals cases of the head-and-eye-form of MCF occurred sporadically at the zoo in European and American bison (Bison bonasus, B. bison' bison, B. bison athabascae), elk (Alces alces), red deer (Cervus elaphus), Père David's deer (Elaphurus davidianus) and again in gaur and banteng. The clinical and pathomorphological observations, including those of prophylactic and tentative treatment are reported. The subspecies of caprinae and alcelaphinae potentionally latently infected with viral agents of MCF kept at the zoo over the reported period are listed. Some details concerning housing, taking care of the animals etc. of the latently infected carriers of the family caprinae and the susceptible species of bovidae and cervidae are also given as far as they are of epidemiological interest. The results of the retrospective analysis and the results of testing paraffin-embedded tissue samples for the presence of ovine herpesvirus-2 (OHV-2)-specific DNA and alcelaphine herpesvirus-1 (AHV-1)-specific DNA from 1964 up to 1997 are discussed. The negative results for OHV-2-specific DNA suggest that MCF at Munich zoo until 1979 could have been "wildebeest-associated", also because until 1974 blue wildebeest (Connochaetes taurinus taurinus) and until 1983 white-tailed gnu (Connochaetes gnou) were kept. However, positive results for OHV-2-specific DNA in the tissues collected from 1985 onwards, strongly suggest the "sheep-associated" MCF. PMID:9810608

  20. Telomerase activity in pleural malignant mesotheliomas.

    PubMed

    Au, Amy Y M; Hackl, Torben; Yeager, Thomas R; Cohen, Scott B; Pass, Harvey I; Harris, Curtis C; Reddel, Roger R

    2011-09-01

    New treatments are needed for malignant pleural mesothelioma (MPM), which currently has a poor prognosis. Cellular immortalisation, one of the hallmarks of cancer, depends on the activity of a telomere length maintenance mechanism (TMM) - either telomerase or alternative lengthening of telomeres (ALT). The TMMs are widely regarded as potential targets for cancer therapies and telomerase inhibitors have entered clinical trials. The aim of this study was to determine what proportion of MPMs use ALT and/or telomerase. Forty-three MPMs from 42 patients were examined for telomerase and ALT activity. Telomerase activity was detected by immunoaffinity purification followed by the telomere repeat amplification protocol (TRAP), and ALT activity was determined by the C-circle assay and by assessing telomere lengths using terminal restriction fragment analyses. We found that 43 of 43 MPMs were telomerase-positive[+] and ALT-negative[-]. Therefore, to investigate whether pleural mesothelial cells are unusually susceptible to activation of telomerase, we examined activation of the TMMs in an in vitro model of cellular immortalisation, in which normal pleural mesothelial cells were transduced with simian virus 40 (SV40) oncogenes. We found that normal mesothelial cells were TMM-negative, and that expression of the SV40 oncogenes did not directly activate telomerase or ALT. Immortalisation, which in this experimental system results from additional genetic changes that have not yet been identified, was accompanied by activation of either TMM. Therefore, pleural mesothelial cells are capable of activating either TMM in vitro, and the observation that 100% of MPMs were telomerase[+] suggests that there are factors in vivo that select for telomerase activity during oncogenesis of this tumour type. We conclude that MPM is a tumour that could be considered for anti-telomerase therapy. PMID:21277646

  1. Green tea: nature's defense against malignancies.

    PubMed

    Butt, Masood Sadiq; Sultan, Muhammad Tauseef

    2009-05-01

    The current practice of introducing phytochemicals to support the immune system or fight against diseases is based on centuries old traditions. Nutritional support is a recent advancement in the domain of diet-based therapies; green tea and its constituents are one of the important components of these strategies to prevent and cure various malignancies. The anti-carcinogenic and anti-mutagenic activities of green tea were highlighted some years ago suggesting that it could reduce the prevalence of cancer and even provide protection. The pharmacological actions of green tea are mainly attributed to polyphenols that includes epigallocatechin-3-gallate (EGCG), epicatechin, epicatechin-3-gallate, epigallocatechin. Green tea and its components effectively mitigate cellular damage arising due to oxidative stress. Green tea is supposed to enhance humoral and cell-mediated immunity, decreasing the risk of certain cancers, and may have certain advantage in treating inflammatory disorders. Much of the cancer chemopreventive properties of green tea are mediated by EGCG that induces apoptosis and promotes cell growth arrest, by altering the expression of cell cycle regulatory proteins, activating killer caspases, and suppressing nuclear factor kappa-B activation. Besides, it regulates and promotes IL-23 dependent DNA repair and stimulates cytotoxic T cells activities in a tumor microenvironment. It also blocks carcinogenesis by modulating the signal transduction pathways involved in cell proliferation, transformation, inflammation and metastasis. The review is intended to highlight the chemistry of green tea, its antioxidant potential, its immunopotentiating properties and mode of action against various cancer cell lines that showed its potential as a chemopreventive agent against colon, skin, lung, prostate, and breast cancer. PMID:19399671

  2. Minimally invasive surgical approach to pancreatic malignancies

    PubMed Central

    Bencini, Lapo; Annecchiarico, Mario; Farsi, Marco; Bartolini, Ilenia; Mirasolo, Vita; Guerra, Francesco; Coratti, Andrea

    2015-01-01

    Pancreatic surgery for malignancy is recognized as challenging for the surgeons and risky for the patients due to consistent perioperative morbidity and mortality. Furthermore, the oncological long-term results are largely disappointing, even for those patients who experience an uneventfully hospital stay. Nevertheless, surgery still remains the cornerstone of a multidisciplinary treatment for pancreatic cancer. In order to maximize the benefits of surgery, the advent of both laparoscopy and robotics has led many surgeons to treat pancreatic cancers with these new methodologies. The reduction of postoperative complications, length of hospital stay and pain, together with a shorter interval between surgery and the beginning of adjuvant chemotherapy, represent the potential advantages over conventional surgery. Lastly, a better cosmetic result, although not crucial in any cancerous patient, could also play a role by improving overall well-being and patient self-perception. The laparoscopic approach to pancreatic surgery is, however, difficult in inexperienced hands and requires a dedicated training in both advanced laparoscopy and pancreatic surgery. The recent large diffusion of the da Vinci® robotic platform seems to facilitate many of the technical maneuvers, such as anastomotic biliary and pancreatic reconstructions, accurate lymphadenectomy, and vascular sutures. The two main pancreatic operations, distal pancreatectomy and pancreaticoduodenectomy, are approachable by a minimally invasive path, but more limited interventions such as enucleation are also feasible. Nevertheless, a word of caution should be taken into account when considering the increasing costs of these newest technologies because the main concerns regarding these are the maintenance of all oncological standards and the lack of long-term follow-up. The purpose of this review is to examine the evidence for the use of minimally invasive surgery in pancreatic cancer (and less aggressive tumors), with particular attention to the oncological results and widespread reproducibility of each technique. PMID:26690680

  3. Minimally invasive surgical approach to pancreatic malignancies.

    PubMed

    Bencini, Lapo; Annecchiarico, Mario; Farsi, Marco; Bartolini, Ilenia; Mirasolo, Vita; Guerra, Francesco; Coratti, Andrea

    2015-12-15

    Pancreatic surgery for malignancy is recognized as challenging for the surgeons and risky for the patients due to consistent perioperative morbidity and mortality. Furthermore, the oncological long-term results are largely disappointing, even for those patients who experience an uneventfully hospital stay. Nevertheless, surgery still remains the cornerstone of a multidisciplinary treatment for pancreatic cancer. In order to maximize the benefits of surgery, the advent of both laparoscopy and robotics has led many surgeons to treat pancreatic cancers with these new methodologies. The reduction of postoperative complications, length of hospital stay and pain, together with a shorter interval between surgery and the beginning of adjuvant chemotherapy, represent the potential advantages over conventional surgery. Lastly, a better cosmetic result, although not crucial in any cancerous patient, could also play a role by improving overall well-being and patient self-perception. The laparoscopic approach to pancreatic surgery is, however, difficult in inexperienced hands and requires a dedicated training in both advanced laparoscopy and pancreatic surgery. The recent large diffusion of the da Vinci(®) robotic platform seems to facilitate many of the technical maneuvers, such as anastomotic biliary and pancreatic reconstructions, accurate lymphadenectomy, and vascular sutures. The two main pancreatic operations, distal pancreatectomy and pancreaticoduodenectomy, are approachable by a minimally invasive path, but more limited interventions such as enucleation are also feasible. Nevertheless, a word of caution should be taken into account when considering the increasing costs of these newest technologies because the main concerns regarding these are the maintenance of all oncological standards and the lack of long-term follow-up. The purpose of this review is to examine the evidence for the use of minimally invasive surgery in pancreatic cancer (and less aggressive tumors), with particular attention to the oncological results and widespread reproducibility of each technique. PMID:26690680

  4. Diagnostic value of neurotrophin expression in malignant pleural effusions

    PubMed Central

    DUYSINX, BERNARD C.; PAULUS, ASTRID; HEINEN, VINCENT; NGUYEN, DELPHINE; HENKET, MONIQUE; CORHAY, JEAN-LOUIS; LOUIS, RENAUD

    2011-01-01

    Neurotrophins (NTs) modulate the growth of human malignancies, including lung cancers. Our prospective study evaluated the accuracy of pleural NTs [nerve growth factor, brain-derived neurotrophic factor (BDNF), neurotrophin 3 (nT3) and 4 (nT4)] levels for differentiating benign from malignant pleural exudates. Levels of NTs were measured by ELISA in 170 patients with non-neutrophilic (<50%) exudative benign or malignant pleurisies diagnosed by pleuroscopy. Fifty-nine benign (9 infections and 50 inflammatory diseases) and 111 malignant (50 extrathoracic tumors, 51 lung cancers and 10 mesotheliomas) pleural exudates were diagnosed by thoracoscopy. Levels of BDNF were significantly higher in malignant than in benign effusions [17 pg/ml (0–367) vs. 8 pg/ml (0–51), p<0.05]. ROC analysis showed an area under the curve of 0.609 (p=0.012; best threshold 44 pg/ml). Pleural BDNF levels were significantly higher in pleural metastasis of pulmonary tumors and in mesothelioma than in pleural benign effusions. Finally, a higher proportion of pleural nT3 was detected in squamous cell lung carcinoma in comparison to that in non-squamous cell lung carcinoma (72.7 vs. 10%, p<0.0001). NTs and particularly BDNF may play a role in the pathogenesis of malignant pleural effusions. PMID:22977602

  5. Reproducibility of Apparent Diffusion Coefficient Measurements in Malignant Breast Masses

    PubMed Central

    Jang, Mijung; Yun, Bo La; Ahn, Hye Shin; Kim, Soo Yeon; Kang, Eunyoung; Kim, Sung-Won

    2015-01-01

    This study aimed to evaluate the reproducibility of apparent diffusion coefficient (ADC) measurements in malignant breast masses, and to determine the influence of mammographic parenchymal density on this reproducibility. Sixty-six patients with magnetic resonance findings of the mass were included. Two breast radiologists measured the ADC of the malignant breast mass and the same area on the contralateral normal breast in each patient twice. The effects of mammographic parenchymal density, histology, and lesion size on reproducibility were also assessed. There was no significant difference in the mean ADC between repeated measurements in malignant breast masses and normal breast tissue. The overall reproducibility of ADC measurements was good in both. The 95% limits of agreement for repeated ADCs were approximately 30.2%-33.4% of the mean. ADC measurements in malignant breast masses were highly reproducible irrespective of mass size, histologic subtype, or coexistence of microcalcifications; however, the measurements tended to be less reproducible in malignant breast masses with extremely dense parenchymal backgrounds. ADC measurements in malignant breast masses are highly reproducible; however, mammographic parenchymal density can potentially influence this reproducibility. PMID:26539016

  6. Hematologic malignancies of the liver: spectrum of disease.

    PubMed

    Tomasian, Anderanik; Sandrasegaran, Kumar; Elsayes, Khaled M; Shanbhogue, Alampady; Shaaban, Akram; Menias, Christine O

    2015-01-01

    The incidence of hematologic malignancies and their extranodal manifestations is continuously increasing. Previously unsuspected hepatic involvement in hematologic malignancies such as Hodgkin disease and non-Hodgkin lymphoma, posttransplant lymphoproliferative disorder, myeloid sarcoma (chloroma), multiple myeloma, Castleman disease, and lymphohistiocytosis may be seen by radiologists. Although the imaging features of more common hepatic diseases such as hepatocellular carcinoma, metastases, and infection may overlap with those of hepatic hematologic malignancies, combining the imaging features with clinical manifestations and laboratory findings can facilitate correct diagnosis. Clinical features that suggest a hematologic neoplasm as the cause of liver lesions include a young patient (<40 years of age), no known history of cancer, abnormal bone marrow biopsy results, fever of unknown origin, and night sweats. Imaging features that suggest hematologic malignancy include hepatosplenomegaly or splenic lesions, vascular encasement by a tumor without occlusion or thrombosis, an infiltrating mass at the hepatic hilum with no biliary obstruction, and widespread adenopathy above and below the diaphragm. Familiarity with the imaging features of hepatic hematologic malignancies permits correct provisional diagnosis and may influence therapeutic management. For example, when biopsy is performed, core biopsy may be needed in addition to fine-needle aspiration so that the tissue architecture of the neoplasm can be discerned. The predominant treatment of hematologic malignancies is chemotherapy or radiation therapy rather than surgery. Online supplemental material is available for this article. PMID:25590389

  7. Fractal dimension analysis of malignant and benign endobronchial ultrasound nodes

    PubMed Central

    2014-01-01

    Background Endobronchial ultrasonography (EBUS) has been applied as a routine procedure for the diagnostic of hiliar and mediastinal nodes. The authors assessed the relationship between the echographic appearance of mediastinal nodes, based on endobronchial ultrasound images, and the likelihood of malignancy. Methods The images of twelve malignant and eleven benign nodes were evaluated. A previous processing method was applied to improve the quality of the images and to enhance the details. Texture and morphology parameters analyzed were: the image texture of the echographies and a fractal dimension that expressed the relationship between area and perimeter of the structures that appear in the image, and characterizes the convoluted inner structure of the hiliar and mediastinal nodes. Results Processed images showed that relationship between log perimeter and log area of hilar nodes was lineal (i.e. perimeter vs. area follow a power law). Fractal dimension was lower in the malignant nodes compared with non-malignant nodes (1.47(0.09), 1.53(0.10) mean(SD), Mann–Whitney U test p?malignant nodes from non-malignant. This parameter could differentiate malignat and non-malignat mediastinic and hiliar nodes. PMID:24920158

  8. A novel mutation in STXBP1 causing epileptic encephalopathy (late onset infantile spasms) with partial respiratory chain complex IV deficiency.

    PubMed

    Barcia, G; Barnerias, C; Rio, M; Siquier-Pernet, K; Desguerre, I; Colleaux, L; Munnich, A; Rotig, A; Nabbout, R

    2013-12-01

    STXBP1 (MUNC18.1), encoding syntaxin binding protein 1, has been reported in Ohtahara syndrome, a rare epileptic encephalopathy with suppression burst pattern on EEG, in patients with infantile spasms and in a few patients with nonsyndromic mental retardation without epilepsy. We report a patient who presented late onset infantile spasms. Epilepsy was controlled but the patient developed severe mental delay. A first diagnosis of mitochondrial disease was based on clinical presentation and on a partial deficit of respiratory chain complex IV, but molecular screening for mitochondrial genes was negative. The sequencing of STXBP1 gene found a de novo nonsense mutation (c.585C>G/p.Tyr195X). This observation widens the clinical spectrum linked to STXBP1 mutations with the description of a patient with late onset infantile spasms. It raises the question of the value of epilepsy genes screening in patients with uncertain, partial or unconfirmed mitochondrial dysfunction. PMID:24095819

  9. Infantile digital fibromatosis-like tumour (inclusion body fibromatosis) of adulthood: report of two cases with ultrastructural and immunocytochemical findings.

    PubMed

    Viale, G; Doglioni, C; Iuzzolino, P; Bontempini, L; Colombi, R; Coggi, G; Dell'Orto, P

    1988-04-01

    Two adult cases of a cutaneous lesion indistinguishable from typical infantile digital fibromatosis are added to the unique similar case so far reported in adulthood. The immunocytochemical localization of vimentin and muscle actin in the proliferating cells confirms their myofibroblastic nature and establishes closer relationships between the adult and the infantile variants of this entity. These two variants, however, appear to be clinically different, since all the adult cases were extradigital and did not recur after surgical excision. The term inclusion body fibromatosis underlines the histological hallmark of the lesion and should be used to identify this entity in place of recurrent infantile digital fibromatosis which does not seem any longer appropriate. PMID:2836293

  10. Histochemical identification of malignant and premalignant lesions

    NASA Astrophysics Data System (ADS)

    Liebow, Charles; Maloney, M. J.

    1991-06-01

    Malignant and transforming cells can be identified by biochemical parameters which can be used to localize lesions in situ for laser surgery. These cells express unique proteins, proteins in unusual quantities, or other biochemical alterations which can be utilized to image lesions of such cells. Several methods have been identified, both in vitro and in vivo, to identify such lesions. Several antibodies were examined for their properties of tissue identification, including CEA, F36/22, and AE1/AE3. F36/22, an antibody developed by M. T. Chu against human breast cancer cells, associated with two lines of oral cancer (KB and HCPC), and against two naturally occurring human oral squamous cell cancers. CEA, an antibody developed against human colon cancer, also reacted against both cell lines and both pathological samples. AE1/AE3, developed against normal fibrous components, also reacted against the samples, but in a much less regular manner. F36/22 associated with the histologically identifiably most dedifferentiated cells at the leading edge of the invading cancer. CEA, on the other hand, associated with more quiescent, older, established cancer cells. This demonstrates that antibodies developed against cancers of different organs can be used to identify a wide variety of cancers, and may have prognostic value. F36/22 coupled to fluorescein was used to identify oral cancer cells. Other properties of cancers and developing cancers can also be exploited to identify cancers, including their over-expression of tyrosine kinase and tyrosine kinase stimulating hormones such as Epidermal Growth Factor (EGF). A model of premalignant lesion produced in the hamster buccal cheek pouch with 6 week application of DMBA over-expresses constitutive tyrosine kinase which can be demonstrated biochemically. This initiated lesion can be promoted to frank cancer by growth factors released in response to laser surgery. Preliminary results suggest that these lesions can be identified by Photofrin II uptake. This work suggests that biochemical properties of cancers can be used to identify premalignant cells.

  11. Carisbamate acutely suppresses spasms in a rat model of symptomatic infantile spasms

    PubMed Central

    Ono, Tomonori; Moshé, Solomon L.; Galanopoulou, Aristea S.

    2011-01-01

    Purpose Infantile spasms are the signature seizures of West syndrome. The conventional treatments for infantile spasms, such as adrenocorticotropic hormone (ACTH) and vigabatrin, are not always effective, especially in symptomatic infantile spasms (SIS). We tested the efficacy of carisbamate, a novel neurotherapeutic drug, to suppress spasms in the multiple-hit rat model of SIS and compared it with phenytoin to determine if its effect is via sodium-channel blockade. Methods Sprague-Dawley rats received right intracerebral infusions of doxorubicin and lipopolysaccharide at postnatal day 3 (PN3) and intraperitoneal p-chlorophenylalanine at PN5. A single intraperitoneal injection of carisbamate was administered at PN4, after the onset of spasms, at the following doses: 10mg/kg (CRS-10); 30 mg/kg (CRS-30); 60 mg/kg (CRS-60) and was compared to vehicle-injected group (VEH). Video-monitoring of PN6–7 CRS-60 or VEH injected pups was also done. Key findings Carisbamate acutely reduced both behavioral spasms (CRS-30 and CRS-60 groups only) and electroclinical spasms, during the first 2–3 post-injection hours, without detectable toxicity or mortality. In contrast, phenytoin (20 or 50 mg/kg) failed to suppress spasms. Significance Our findings provide preclinical evidence that carisbamate displays acute anticonvulsive effect on spasms through a sodium channel-independent mechanism. As spasms in the multiple-hit rat model are refractory to ACTH and transiently sensitive to vigabatrin, carisbamate may constitute a candidate new therapy for SIS, including the ACTH-refractory spasms. Further confirmation with clinical studies is needed. PMID:21770922

  12. Adrenal Function Testing Following Hormone Therapy for Infantile Spasms: Case Series and Review of Literature

    PubMed Central

    Mytinger, John R.; Bowden, Sasigarn A.

    2015-01-01

    Prednisolone and adrenocorticotropic hormone (ACTH) are “hormone” therapies for infantile spasms. There is limited data on the occurrence of decreased adrenal reserve or signs of clinical adrenal insufficiency after hormone therapy. This is a retrospective medical record review of patients referred to our Infantile Spasms Program. Our standardized infantile spasms management guideline began in September 2012 and initially included a post-hormone laboratory assessment of adrenal function. Medical records were assessed for hormone treatments, adrenal function testing, and signs of adrenal insufficiency. Forty-two patients who received one or both hormone therapies met inclusion criteria. A post-hormone laboratory assessment of adrenal function was done in 14 patients. Of these 14 patients, 2 had an abnormal laboratory assessment of adrenal function, both by adrenal stimulation testing?–?one after ACTH and one after prednisolone. One patient received hydrocortisone replacement and the other received stress dose hydrocortisone as needed; neither patient developed signs of adrenal insufficiency. Another patient treated with both types of hormone therapy in tandem, who did not have a post-hormone laboratory assessment, developed signs of mild adrenal insufficiency and required replacement hydrocortisone. Our study suggests that adrenal suppression can occur after modern hormone therapy regimens. We found two patients with abnormal adrenal function testing after hormone therapy and another patient with signs adrenal insufficiency. Given the seriousness of adrenal crisis, caregiver education on the signs of adrenal insufficiency is critical. Greater vigilance may be indicated in patients receiving both types of hormone therapy in tandem. Although a routine post-hormone laboratory assessment of adrenal function may not be feasible in all patients, replacement or stress dose hydrocortisone is necessary for all patients with suspected adrenal insufficiency. PMID:26696958

  13. Multicentric primary malignant melanomas of the choroid: two separate malignant melanomas of the choroid and two uveal naevi in one eye.

    PubMed Central

    Völcker, H. E.; Naumann, G. O.

    1978-01-01

    Two completely separate malignant melanomas of the choroid occurred in 1 eye containing 2 additional uveal naevi. Review of the literature disclosed 7 further patients with unilateral multicentric malignant melanomas of the choroid and 11 bilateral multicentric malignant melanomas of the uvea. General aspects of multicentric primary neoplasia are discussed and an interpretation is attempted. Images PMID:666990

  14. Accumulation of mitochondrial ATP synthase subunit c in muscle in a patient with neuronal ceroid lipofuscinosis (late infantile form).

    PubMed

    Umehara, F; Higuchi, I; Tanaka, K; Niiyama, T; Ezaki, J; Kominami, E; Osame, M

    1997-06-01

    We report a case late infantile neuronal ceroid lipofuscinosis (NCL). Abnormal granules were found in the skeletal muscle fibers, Schwann cells, perineurial cells, endothelial cells, fibroblasts, and perivascular smooth muscle cells in the sural nerve. Electron microscopy revealed that these granules showed fingerprint profiles, curvilinear profiles or membrane-bound membranous structures. Acid phosphatase reaction was increased in these cells. Immunohistochemical studies for mitochondrial ATP synthase subunit c showed a strong reaction in these cells, suggesting abnormal accumulation of subunit c. Immunohistochemistry for subunit c in muscle may be useful in the diagnosis of late infantile NCL. PMID:9194903

  15. Hypofibrinogenemia caused by adrenocorticotropic hormone for infantile spasms: a case report.

    PubMed

    Kamei, Atsushi; Araya, Nami; Akasaka, Manami; Mizuma, Kanako; Asami, Maya; Tanifuji, Sachiko; Chida, Shoichi

    2015-01-01

    We report the case of a 7-month-old boy who developed hypofibrinogenemia (66.6 mg/dL; reference value, 170-405 mg/dL) during adrenocorticotropic hormone (ACTH) therapy for infantile spasms. Although the patient showed no clinical signs of a bleeding diathesis, we recommend that plasma fibrinogen levels should be monitored during ACTH therapy, which should be discontinued when fibrinogen levels fall below hemostatic levels (60.0mg/dL) or when bleeding tendencies are recognized. PMID:24735983

  16. Infantile spasms syndrome, West syndrome and related phenotypes: what we know in 2013.

    PubMed

    Pavone, Piero; Striano, Pasquale; Falsaperla, Raffaele; Pavone, Lorenzo; Ruggieri, Martino

    2014-10-01

    The current spectrum of disorders associated to clinical spasms with onset in infancy is wider than previously thought; accordingly, its terminology has changed. Nowadays, the term Infantile spasms syndrome (ISs) defines an epileptic syndrome occurring in children younger than 1 year (rarely older than 2 years), with clinical (epileptic: i.e., associated to an epileptiform EEG) spasms usually occurring in clusters whose most characteristic EEG finding is hypsarrhythmia [the spasms are often associated with developmental arrest or regression]. The term West syndrome (WS) refers to a form (a subset) of ISs, characterised by the combination of clustered spasms and hypsarrhythmia on an EEG and delayed brain development or regression [currently, it is no longer required that delayed development occur before the onset of spasms]. Less usually, spasms may occur singly rather than in clusters [infantile spasms single-spasm variant (ISSV)], hypsarrhythmia can be (incidentally) recorded without any evidence of clinical spasms [hypsarrhythmia without infantile spasms (HWIS)] or typical clinical spasms may manifest in absence of hypsarrhythmia [infantile spasms without hypsarrhythmia (ISW)]. There is a growing evidence that ISs and related phenotypes may result, besides from acquired events, from disturbances in key genetic pathways of brain development: specifically, in the gene regulatory network of GABAergic forebrain dorsal-ventral development, and abnormalities in molecules expressed at the synapse. Children with these genetic associations also have phenotypes beyond epilepsy, including dysmorphic features, autism, movement disorders and systemic malformations. The prognosis depends on: (a) the cause, which gives origin to the attacks (the complex malformation forms being more severe); (b) the EEG pattern(s); (c) the appearance of seizures prior to the spasms; and (d) the rapid response to treatment. Currently, the first-line treatment includes the adrenocorticotropic hormone ACTH and vigabatrin. In the near future the gold standard could be the development of new therapies that target specific pathways of pathogenesis. In this article we review the past and growing number of clinical, genetic, molecular and therapeutic discoveries on this expanding topic. PMID:24268986

  17. FTIR study on the normal and malignant gastric tissues

    NASA Astrophysics Data System (ADS)

    Cheng, Cungui; Wang, Bei; Liu, Hinghai; Zhu, Peixi; Li, Danting; Chen, Qingjie

    2006-01-01

    By experimenting with Fourier transform infrared spectroscopy (FTIR), it was found that FTIR yielded much better results and faster determination of normal and malignant gastric tissues when accompanied with OMNI-sampler. The results showed that there were obvious and regularity differences between FTIR spectra of them in spectral parameters such as frequency, intensity and shape of the bands etc. They indicated significant differences of content, structure and conformation of proteins, nucleic acids and lipids in normal and malignant gastric tissues. The probability found by the results of goodness-of-fit tests of frequency of the bands in the second derivative FTIR, between each of the normal and malignant gastric tissues was less than 0.01. This result was found to be significant. The present results suggested that FTIR could show the properties of normal and malignant gastric tissues in the molecular level. It contains the ability to supply rich and reliable information to investigation of normal and malignant gastric tissues and can be used as a convenient and reliable diagnostic tool for tumors.

  18. Extra-Neural Metastases of Malignant Gliomas: Myth or Reality?

    PubMed Central

    Beauchesne, Patrick

    2011-01-01

    Malignant gliomas account for approximately 60% of all primary brain tumors in adults. Prognosis for these patients has not significantly changed in recent years— despite debulking surgery, radiotherapy and cytotoxic chemotherapy—with a median survival of 9–12 months. Virtually no patients are cured of their illness. Malignant gliomas are usually locally invasive tumors, though extra-neural metastases can sometimes occur late in the course of the disease (median of two years). They generally appear after craniotomy although spontaneous metastases have also been reported. The incidence of these metastases from primary intra-cranial malignant gliomas is low; it is estimated at less than 2% of all cases. Extra-neural metastases from gliomas frequently occur late in the course of the disease (median of two years), and generally appear after craniotomy, but spontaneous metastases have also been reported. Malignant glioma metastases usually involve the regional lymph nodes, lungs and pleural cavity, and occasionally the bone and liver. In this review, we present three cases of extra-neural metastasis of malignant gliomas from our department, summarize the main reported cases in literature, and try to understand the mechanisms underlying these systemic metastases. PMID:24212625

  19. Optical discrimination between malignant and benign breast lesions

    NASA Astrophysics Data System (ADS)

    Quarto, Giovanna; Pifferi, Antonio; Cubeddu, Rinaldo; Ieva, Francesca; Paganoni, Anna Maria; Abbate, Francesca; Cassano, Enrico; Taroni, Paola

    2015-07-01

    Time domain multi-wavelength (635 to 1060 nm) optical mammography was performed on 82 subjects with breast lesions (45 malignant and 38 benign lesions). A perturbative approach based on the high-order calculation of the pathlength of photons inside the lesion was applied to estimate differences between lesion and average healthy tissue of the same breast in terms of: i) absorption properties, and ii) concentration of the major tissue constituents (oxy- and deoxy-hemoglobin, water, lipid and collagen). The absorption difference ??a between lesion and healthy tissue is significantly different for malignant vs. benign lesions at all wavelengths. Logistic regression fitted to the absorption data identifies 975 nm as the key wavelength to discriminate malignant from benign lesions. When the difference in tissue composition between lesion and healthy tissue is considered, malignant lesions are characterized by significantly higher collagen content than benign lesions. Also the best model for the discrimination of malignant lesions obtained applying regression logistic to tissue composition is based only on collagen. Including demographic information into the model improves its specificity.

  20. Malignancy-associated haemophagocytic lymphohistiocytosis in children and adolescents.

    PubMed

    Lehmberg, Kai; Sprekels, Björn; Nichols, Kim E; Woessmann, Wilhelm; Müller, Ingo; Suttorp, Meinolf; Bernig, Toralf; Beutel, Karin; Bode, Sebastian F N; Kentouche, Karim; Kolb, Reinhard; Längler, Alfred; Minkov, Milen; Schilling, Freimut H; Schmid, Irene; Vieth, Simon; Ehl, Stephan; Zur Stadt, Udo; Janka, Gritta E

    2015-08-01

    Haemophagocytic lymphohistiocytosis (HLH) in the context of malignancy is mainly considered a challenge of adult haematology. While this association is also observed in children, little is known regarding inciting factors, appropriate treatment and prognosis. We retrospectively analysed 29 paediatric and adolescent patients for presenting features, type of neoplasm or preceding chemotherapy, treatment and outcome. Haemophagocytic lymphohistiocytosis was considered triggered by the malignancy (M-HLH) in 21 patients, most of whom had T- (n = 12) or B-cell neoplasms (n = 7), with Epstein-Barr virus as a co-trigger in five patients. In eight patients, HLH occurred during chemotherapy (Ch-HLH) for malignancy, mainly acute leukaemias (n = 7); an infectious trigger was found in seven. In M- and Ch-HLH, median overall survival was 1·2 and 0·9 years, and the 6 month survival rates were 67% and 63%, respectively. Seven of 11 deceased M-HLH patients exhibited active malignancy and HLH at the time of death, while only two out of five deceased Ch-HLH patients had evidence of active HLH. To overcome HLH, malignancy- and HLH-directed treatments were administered in the M-HLH cohort; however, it was not possible to determine superiority of one approach over the other. For Ch-HLH, treatment ranged from postponement of chemotherapy to the use of etoposide-containing regimens. PMID:25940575

  1. Integrative metabonomics as potential method for diagnosis of thyroid malignancy

    PubMed Central

    Tian, Yuan; Nie, Xiu; Xu, Shan; Li, Yan; Huang, Tao; Tang, Huiru; Wang, Yulan

    2015-01-01

    Thyroid nodules can be classified into benign and malignant tumors. However, distinguishing between these two types of tumors can be challenging in clinics. Since malignant nodules require surgical intervention whereas asymptomatic benign tumors do not, there is an urgent need for new techniques that enable accurate diagnosis of malignant thyroid nodules. Here, we used 1H NMR spectroscopy coupled with pattern recognition techniques to analyze the metabonomes of thyroid tissues and their extracts from thyroid lesion patients (n?=?53) and their adjacent healthy thyroid tissues (n?=?46). We also measured fatty acid compositions using GC?FID/MS techniques as complementary information. We demonstrate that thyroid lesion tissues can be clearly distinguishable from healthy tissues, and malignant tumors can also be distinguished from the benign tumors based on the metabolic profiles, both with high sensitivity and specificity. In addition, we show that thyroid lesions are accompanied with disturbances of multiple metabolic pathways, including alterations in energy metabolism (glycolysis, lipid and TCA cycle), promotions in protein turnover, nucleotide biosynthesis as well as phosphatidylcholine biosynthesis. These findings provide essential information on the metabolic features of thyroid lesions and demonstrate that metabonomics technology can be potentially useful in the rapid and accurate preoperative diagnosis of malignant thyroid nodules. PMID:26486570

  2. Hypercalcemia of Malignancy: An Update on Pathogenesis and Management

    PubMed Central

    Mirrakhimov, Aibek E.

    2015-01-01

    Hypercalcemia of malignancy is a common finding typically found in patients with advanced stage cancers. We aimed to provide an updated review on the etiology, pathogenesis, clinical presentation, and management of malignancy-related hypercalcemia. We searched PubMed/Medline, Scopus, Embase, and Web of Science for original articles, case reports, and case series articles focused on hypercalcemia of malignancy published from 1950 to December 2014. Hypercalcemia of malignancy usually presents with markedly elevated calcium levels and therefore, usually severely symptomatic. Several major mechanisms are responsible for the development of hypercalcemia of malignancy including parathyroid hormone-related peptide-mediated humoral hypercalcemia, osteolytic metastases-related hypercalcemia, 1,25 Vitamin D-mediated hypercalcemia, and parathyroid hormone-mediated hypercalcemia in patients with parathyroid carcinoma and extra parathyroid cancers. Diagnosis should include the history and physical examination as well as measurement of the above mediators of hypercalcemia. Management includes hydration, calcitonin, bisphosphonates, denosumab, and in certain patients, prednisone and cinacalcet. Patients with advanced underlying kidney disease and refractory severe hypercalcemia should be considered for hemodialysis. Hematology or oncology and palliative care specialists should be involved early to guide the options of cancer targeted therapies and help the patients and their closed ones with the discussion of comfort-oriented care. PMID:26713296

  3. Serous Ovarian Carcinoma Recurring as Malignant Mixed Mullerian Tumor

    PubMed Central

    Hale, Demir; Senem, Demiroz Ahu; Ovgu, Aydin; Hakan, Erenel; Sennur, Ilvan; Zerrin, Calay; Fuat, Demirkiran

    2015-01-01

    Only five cases of recurrence of malignant mixed Mullerian tumor (carcinosarcoma) from the ovarian carcinoma have been published in the literature to our knowledge. A 64-year-old woman first underwent a total abdominal hysterectomy and bilateral salpingo-oophorectomy because of pelvic mass. Histological diagnosis was serous papillary carcinoma of the left ovary. After six courses of chemotherapy, CA125 level returned to normal range. However, she had persistent multiple mediastinal and para-aortic lymphadenopathies in spite of additional six courses of chemotherapy. Then she underwent the second operation about 2 years after primary surgery. Multiple excisional biopsies were taken from subcutaneous tissue, over the bowels and the left external iliac artery. The histopathological diagnosis which was confirmed by immunohistochemical study was malignant mixed Mullerian tumor for all metastatic foci. A rare case of ovarian serous papillary carcinoma recurring as malignant mixed Mullerian tumor is reported. PMID:26713165

  4. Malignant conversion of oral submucous fibrosis in surgically treated case.

    PubMed

    Arora, Rajendra; Adwani, Dwarkadas; Naphade, Milind; Bhagat, Bhushan; Qureshi, Abdul Qahar

    2014-10-01

    Oral submucous fibrosis (OSMF) is an insidious chronic disease affecting any part of the oral cavity and sometimes the pharynx with epithelial atrophy leading to stiffness of the oral mucosa, causing trismus and inability to eat. However a more serious complication of this disease is the risk of the development of oral carcinoma. We reported the histopathologically proven case of OSMF with initial interincisal mouth opening 2mm which was treated surgically with nasolabial flap technique but failed to follow up and could not do active mouth opening exercises. Malignant conversion of OSMF was seen in this case. This is required to assess the progress and evaluate any malignant transformation at the earliest. So, the importance of active co-operation and frequent follow up cannot be overemphasized. The purpose of this study is to emphasize the importance of regular follow up and frequent biopsies to facilitate oral examination and to check any malignant conversion after the surgery. PMID:25478469

  5. Germline ETV6 mutations in familial thrombocytopenia and hematologic malignancy

    PubMed Central

    Zhang, Michael Y; Churpek, Jane E; Keel, Siobán B; Walsh, Tom; Lee, Ming K; Loeb, Keith R; Gulsuner, Suleyman; Pritchard, Colin C; Sanchez-Bonilla, Marilyn; Delrow, Jeffrey J; Basom, Ryan S; Forouhar, Melissa; Gyurkocza, Boglarka; Schwartz, Bradford S; Neistadt, Barbara; Marquez, Rafael; Mariani, Christopher J; Coats, Scott A; Hofmann, Inga; Lindsley, R Coleman; Williams, David A; Abkowitz, Janis L; Horwitz, Marshall S; King, Mary-Claire; Godley, Lucy A; Shimamura, Akiko

    2015-01-01

    We report germline missense mutations in ETV6 segregating with the dominant transmission of thrombocytopenia and hematologic malignancy in three unrelated kindreds, defining a new hereditary syndrome featuring thrombocytopenia with susceptibility to diverse hematologic neoplasms. Two variants, p.Arg369Gln and p.Arg399Cys, reside in the highly conserved ETS DNA-binding domain. The third variant, p.Pro214Leu, lies within the internal linker domain, which regulates DNA binding. These three amino acid sites correspond to hotspots for recurrent somatic mutation in malignancies. Functional studies show that the mutations abrogate DNA binding, alter subcellular localization, decrease transcriptional repression in a dominant-negative fashion and impair hematopoiesis. These familial genetic studies identify a central role for ETV6 in hematopoiesis and malignant transformation. The identification of germline predisposition to cytopenias and cancer informs the diagnosis and medical management of at-risk individuals. PMID:25581430

  6. Oral malignant melanoma: Report of three cases with literature review

    PubMed Central

    Gupta, Shalini; Tandon, Ankita; Ram, Hari; Gupta, O. P.

    2015-01-01

    Primary oral melanoma is known to be an extremely rare and aggressive neoplasm arising from the mucosal epithelium of the oral cavity especially upper jaw (palate or alveolar gingivae). Malignant melanoma that does not originate in the skin is a very rare disease and is considered one of the most deadly of all human neoplasms. Oral malignant melanoma (OMM) represents about 1% of all melanomas and approximately 0.5% of all oral malignancies. OMM has been reported in patients aged 20 to 80 years and has a male predilection. Because most mucosal melanotic lesions are painless in their early stages, so delayed recognition and subsequent treatment result in worst prognosis. Here, we report three cases with significant heterogeneity in morphological features and biologic behavior.

  7. Peritoneal malignant mesothelioma metastatic to supraclavicular lymph nodes.

    PubMed

    Zannella, Stefano; Testi, Maria Adele; Cattoretti, Giorgio; Pelosi, Giuseppe; Zucchini, Nicola

    2014-09-01

    Distinguishing between malignant mesothelioma and reactive mesothelial hyperplasia is often inestimable, but may be a challenging gauntlet for pathologists. A 62-year-old man underwent appendectomy after the identification of a peritoneal mass and the histological examination showed mesothelial proliferation along the appendix surface with no clear images of infiltration. After a few months the patient developed mediastinal and supraclavicular lymphadenopathies, and a nodal biopsy showed mesothelial cell proliferation invading lymphatic sinuses, consistent with the cells seen in the abdominal cavity. Since overt morphologic criteria for malignancy were lacking and reactive mesothelial cell deposits have been documented in lymph nodes, a molecular investigation of the CDKN2A (henceforth simply p16) gene status via fluorescence in situ hybridization was performed, which showed homozygous deletion in 100% tumor cells. These data ruled out the hypothesis of reactive mesothelial cells inclusion in lymph nodes, thus confirming the diagnosis of epithelioid malignant mesothelioma. PMID:24474244

  8. Primary malignant melanoma of the trachea: A case report

    PubMed Central

    IMAI, HISAO; KIYOHARA, YOSHIO; YOSHIKAWA, SHUSUKE; KUSUTANI, NAO; ONO, AKIRA; TAIRA, TETSUHIKO; KENMOTSU, HIROTSUGU; HARADA, HIDEYUKI; NAITO, TATEAKI; MURAKAMI, HARUYASU; SANO, TAKEHISA; FUJI, HIROSHI; ENDO, MASAHIRO; NAKAJIMA, TAKASHI; TAKAHASHI, TOSHIAKI

    2015-01-01

    Primary cancer of the trachea is rare and accounts for only 0.1–0.4% of all newly diagnosed respiratory tract cancers, worldwide. In the present study, a case of primary tracheal malignant melanoma, a particularly rare type of cancer, is reported. A 68-year-old male presented with a cough and bloody sputum. A chest computed tomography scan revealed a 25×20×15-mm tracheal tumor, located immediately above the carina, which reduced the cross-sectional area of the trachea by ~90%. Histopathological analysis of biopsy specimens determined a diagnosis of malignant melanoma. The patient was treated with argon plasma coagulation and chemoradiotherapy, which restored airway patency, however, metastasis was detected in the lungs. The patient refused further treatment and received palliative care. Subsequently, the patient succumbed to the disease within four months. Thus, although primary malignant melanoma of the trachea is extremeley rare, the possibility should be considered during diagnosis. PMID:25624894

  9. Malignant Conversion of Oral Submucous Fibrosis in Surgically Treated Case

    PubMed Central

    Arora, Rajendra; Adwani, Dwarkadas; Naphade, Milind; Qureshi, Abdul Qahar

    2014-01-01

    Oral submucous fibrosis (OSMF) is an insidious chronic disease affecting any part of the oral cavity and sometimes the pharynx with epithelial atrophy leading to stiffness of the oral mucosa, causing trismus and inability to eat. However a more serious complication of this disease is the risk of the development of oral carcinoma. We reported the histopathologically proven case of OSMF with initial interincisal mouth opening 2mm which was treated surgically with nasolabial flap technique but failed to follow up and could not do active mouth opening exercises. Malignant conversion of OSMF was seen in this case. This is required to assess the progress and evaluate any malignant transformation at the earliest. So, the importance of active co-operation and frequent follow up cannot be overemphasized. The purpose of this study is to emphasize the importance of regular follow up and frequent biopsies to facilitate oral examination and to check any malignant conversion after the surgery. PMID:25478469

  10. Current advances in radiotherapy of head and neck malignancies

    PubMed Central

    Roopashri, G; Baig, Muqeet

    2013-01-01

    Necessity is the mother of all inventions. This is also true in case of cancer therapy. With increasing incidence of head and neck malignancies, remarkable developments have been made towards cancer development and treatment which continues to be a major challenge. Approximately fifty percent of all cancer patients receive radiotherapy which contributes towards forty percent of curative treatment for cancer. New developments in radiation oncology have helped to improve outlook for patients and find more effective treatment. With the advent of new technologies, radiotherapy seems to be promising in patients with head and neck malignancies these advancements include Altered fractionation, Three-dimensional conformal radiotherapy, Intensity-modulated radiotherapy, Image Guided Radiotherapy, Stereotactic radiation, Charged-particle radiotherapy, and Intraoperative radiotherapy. How to cite this article: Roopashri G, Baig M. Current advances in radiotherapy of head and neck malignancies. J Int Oral Health 2013; 5(6):119-23 . PMID:24453456

  11. [Incidence of malignant soft tissue tumors (sarcomas) after previous radiotherapy].

    PubMed

    Hernandez-Richter, T; Heiss, M M; Bubb, C; Jauch, K W

    1996-01-01

    The causal agent for sarcomas is mostly unknown. Unlike solid epithelial carcinomas, the correlation to the exposition to carcinogenic agents is unknown. Besides hereditary neurofibromatosis ("Recklinghausen"), radiation therapy has been reported to induce malignant tumors. In this retrospective study during the last 10 years we observed that in 7 of 356 (approximately 2%) patients treated for sarcomas in our Department of Surgery, the sarcoma was located in the area where radiation therapy had been given earlier for another primary malignant tumor. The interval between this radiation therapy and the diagnosis of sarcoma was 9 to 30 years, corroborated by findings in the literature based on approximately 100 radiation-induced tumors. The median survival time after diagnosis of sarcoma was 3 years. Because radiation therapy is often used in the treatment of malignant tumors this late complication is a clinically relevant problem in long-time survival. PMID:9064470

  12. Head mass in chronic pancreatitis: Inflammatory or malignant

    PubMed Central

    Dutta, Amit K; Chacko, Ashok

    2015-01-01

    Chronic pancreatitis increases the risk of developing pancreatic cancer. This often presents as a mass lesion in the head of pancreas. Mass lesion in the head of pancreas can also occur secondary to an inflammatory lesion. Recognising this is crucial to avoid unnecessary surgery. This is sometimes difficult as there is an overlap in clinical presentation and conventional computed tomography (CT) abdomen findings in inflammatory and malignant mass. Advances in imaging technologies like endoscopic ultrasound in conjunction with techniques like fine needle aspiration, contrast enhancement and elastography as well as multidetector row CT, magnetic resonance imaging and positron emission tomography scanning have been shown to help in distinguishing inflammatory and malignant mass. Research is ongoing to develop molecular techniques to help characterise focal pancreatic mass lesions. This paper reviews the current status of imaging and molecular techniques in differentiating a benign mass lesion in chronic pancreatitis and from malignancy. PMID:25789097

  13. The differentiation between malignant and non-malignant breast tissues using elastic and inelastic scattering of synchrotron radiation

    NASA Astrophysics Data System (ADS)

    Ryan, Elaine A.; Farquharson, Michael J.

    2010-07-01

    The aim of this work was to investigate the differences in composition between malignant and non-malignant breast tissue. 38 invasive ductal carcinomas and 45 non-malignant breast tissues were measured, each being mounted in cylindrical sample holders of volume 25 mm 2. The experiments were performed at the European Synchrotron Radiation Facility (ESRF) at Grenoble, France. A monochromatic beam of 10 keV was used, focussed to a 0.5 mm×0.5 mm rectangular area on the sample. Elastic and inelastic scattered photons were collected at an angle of 120°. A novel technique was used to find the mean atomic numbers of the tissues ( Z¯). A CT scanner that has been calibrated with an ED phantom was used to find the Z¯ of 10 gels. These were composed of a gelatine base, with low concentrations of copper added to increase the Z¯ values by an incremental amount. These were then used to calibrate the scattering measurement system. The area of the elastic and inelastic scatter peaks were found using peak fitting software and the ratio of these two areas was obtained. The data was shown to be non-parametric, and was therefore analysed using a Mann-Whitney test. Using this analysis the difference between non-malignant and malignant tissues was found to be extremely significant, with a 2-tailed p-value of <0.0001. The absolute Z¯ values were also analysed.

  14. Marked variation in malignant transformation rates of oral leukoplakia.

    PubMed

    Anderson, Aisling; Ishak, Nurul

    2015-12-01

    Data sourcesSearches were carried out in the Medline, Embase and PubMed databases in July 2014 with a date range, 1960-2013.Study selectionObservational cohort studies (either prospective or retrospective) were included. Studies following identical cohorts, case control studies, clinical trials, interventional studies, laboratory studies, experimental studies, studies with no follow-up data, studies of pre-leukoplakia or snuff-induced lesions were excluded.Data extraction and synthesisThe databases were searched by one reviewer who also screened the studies and evaluated them against the inclusion criteria. Final decision on both inclusion and exclusion of the papers was agreed upon by both authors.ResultsA total of 24 studies were included in this review, involving 12,103 patients. Of the 24 studies included 14 were retrospective. Studies were analysed by subgroup, allowing the authors to identify the rate of malignant transformation as 14.9% with a range of 0.13% to 34%. Only 11 studies gave information on the site of malignant transformation; the most common site was the buccal mucosa. For buccal mucosa the malignant transformation was 3.53%, compared to 24.22% for the tongue. Homogenous oral leukoplakia (OL) was most common, however non-homogenous types showed a higher rate of transformation of 13.1%. There was an increased risk of malignant transformation with age. Most studies demonstrated that there is a higher risk of transformation in the female population.ConclusionsMalignant transformation rate of OL varies from 0.13 to 34% across the 24 studies reviewed here. The authors identified clear risk factors for malignant transformation of oral leukoplakia, including location (tongue), appearance (non-homogenous), increased age and female gender. There was little evidence that surgical intervention had any benefit in reducing the risk of transformation. PMID:26680515

  15. Motexafin gadolinium induces oxidative stress and apoptosis in hematologic malignancies.

    PubMed

    Evens, Andrew M; Balasubramanian, Lakshmi; Gordon, Leo I

    2005-07-01

    Redox mechanisms have been shown to be important in malignant cell survival and are a system that may be modified for the treatment of hematologic malignancies. Motexafin gadolinium (MGd) is a synthetic expanded porphyrin that selectively accumulates in tumor cells and oxidizes various intracellular metabolites, including ascorbate, nicotinamide adenine dinucleotide phosphate, glutathione, and protein thiols, to generate reactive oxygen species in a process known as futile redox cycling. The rationale for its use in hematologic malignancies is that, like naturally occurring porphyrins, it tends to concentrate selectively in cancer cells, and it has a novel mechanism of action of inducing redox stress and triggering apoptosis in a broad range of malignancies. MGd induces apoptosis in B-cell non-Hodgkin's lymphoma, chronic lymphocytic leukemia, and highly resistant myeloma cell lines. Furthermore, MGd is additive or synergistic with ionizing radiation, several chemotherapy agents, and rituximab in vitro and in vivo tumor models. Through gene expression profiling, various stress-related genes are upregulated in response to MGd, including genes encoding metallothioneins, heat shock proteins, and heme oxygenase. Preliminary results from clinical trials with MGd in hematopoietic malignancies have shown that it is well tolerated, with minimal hematologic side effects in both; it has single agent activity in very heavily pretreated chronic lymphocytic leukemia /small lymphocytic lymphoma patients, and it has induced prompt complete remissions in combination with 90Yttrium-ibritumomab (Y-90 Zevalin; Biogen Idec Inc., Cambridge, MA) for relapsed non-Hodgkin's lymphoma in the first two cohorts of patients enrolled. Various clinical trials studying MGd as a single agent and in combination with radiation and/or chemotherapy for the treatment of hematologic malignancies are ongoing. PMID:15967082

  16. Contemporary Systemic Therapy for Urologic Malignancies in Geriatric Patients.

    PubMed

    Zhao, Bo; Grivas, Petros D

    2015-11-01

    Current data on systemic therapy in geriatric populations with genitourinary malignancies are largely derived from retrospective analyses of prospectively conducted trials or retrospective reviews. Although extrapolation of these data to real-world patients should be cautious, patients aged 65 years or older with good functional status and minimal comorbidities seem to enjoy similar survival benefit from therapy as their younger counterparts. Chronologic age alone should generally not be used to guide management decisions. Comprehensive geriatric assessment tools and prospective studies in older adults integrating comprehensive geriatric assessment can shed light on the optimal management of urologic malignancies in this population. PMID:26476122

  17. A case of primary choroidal malignant melanoma in a cat.

    PubMed

    Bourguet, Aurélie; Piccicuto, Virginie; Donzel, Elise; Carlus, Marine; Chahory, Sabine

    2015-07-01

    This report describes the clinical presentation, diagnosis, histological lesions, and prognosis of a primary choroidal malignant melanoma in a 15-year-old cat. The animal was presented for unilateral blindness. On ocular examination, a raised pigmented mass protruding from the posterior pole into the vitreous body was observed by diffuse transillumination and indirect ophthalmoscopy. Ocular ultrasound and computer tomography (CT) scan confirmed localization of the tumor to the posterior segment. The diagnosis of primary choroidal melanoma was confirmed by histopathology after enucleation. To our knowledge, this is the first reported case of a feline malignant melanoma with a primary choroidal localization without iris involvement. PMID:25399839

  18. Coexistent Malignant Peripheral Nerve Sheath Tumor and Lateral Spinal Meningoceles

    PubMed Central

    Bhoir, Lata; Nichat, Pramod; Chug, Ashish; Verma, Harish

    2012-01-01

    Malignant peripheral nerve sheath tumor (MPNST) is a malignant spindle cell tumor of the soft tissue thought to be derived from the components of nerve sheath. MPNSTs are mainly located in the buttocks, thighs, brachial plexus, and paraspinal region. The objective of this article is to describe a case of neurofibromatosis type 1 who developed neurofibrosarcoma of the right lateral thoracic nerve with thoracic meningoceles, a rare coincidental finding which has not yet been reported in the English medical literature, and how both the conditions were managed in the same sitting. PMID:23066463

  19. Malignant Extra Renal Rhabdoid Tumour Presenting as Central Airway Obstruction

    PubMed Central

    Bal, Amanjit; Agarwal, Ritesh; Das, Ashim

    2014-01-01

    Rhabdoid tumours are one of the most aggressive childhood neoplasms associated with high mortality. The commonest age group affected is children less than five years of age. Rhabdoid tumour presenting as an endoluminal tracheal mass leading to central airway obstruction has not been previously reported. We describe the case of a 17-year-old male patient where malignant rhabdoid tumour masqueraded as bronchial asthma leading to a delayed diagnosis of upper airway obstruction by tracheal growth. Histopathological examination and immunohistochemistry confirmed the diagnosis of malignant rhabdoid tumour. PMID:25243090

  20. Malignant melanoma in the foot of a horse.

    PubMed

    Honnas, C M; Liskey, C C; Meagher, D M; Brown, D; Luck, E E

    1990-09-15

    A 24-year-old horse had a malignant melanoma of the right forefoot. Because surgical excision of the melanoma was incomplete, as determined by histologic examination of the excised tissue margins, the tumor margins were injected with a matrix therapeutic implant containing cis-diamminedichloroplatinum, epinephrine, and purified bovine collagen matrix. The foot healed and the horse remained clinically free of disease for 26 months before recurrence of malignant melanoma. Surgical exploration of the digit revealed extensive involvement of the foot, and the horse was euthanatized. PMID:2211329

  1. Role of stenting in gastrointestinal benign and malignant diseases

    PubMed Central

    Mangiavillano, Benedetto; Pagano, Nico; Arena, Monica; Miraglia, Stefania; Consolo, Pierluigi; Iabichino, Giuseppe; Virgilio, Clara; Luigiano, Carmelo

    2015-01-01

    Advances in stents design have led to a substantial increase in the use of stents for a variety of digestive diseases. Initially developed as a non-surgical treatment for palliation of esophageal cancer, the stents now have an emerging role in the management of malignant and benign conditions as well as in all segments of the gastrointestinal tract. In this review, relevant literature search and expert opinions have been used to evaluate the key-role of stenting in gastrointestinal benign and malignant diseases. PMID:25992186

  2. Concurrence of malignant fibrohistiocytoma and Takayasu arteritis: a case report.

    PubMed

    Du, Jin-Feng; Chen, Jin-Wei; Li, Fen; Tian, Jing; Xie, Xi; Mao, Ni

    2012-10-01

    Takayasu arteritis (TA) is a type of systemic large-vessel vasculitis that usually affects the aorta and its major branches. It remains unrecognized owing to delayed diagnosis (Boltin et al. in Rheumatol Int 27(10):985-987, 2007) and non-characteristic clinical features. It has been described in association with many autoimmune diseases, such as inflammatory digestive tract diseases. However, report of TA associated with tumors, especially malignant tumors, are rare. We here presented a case diagnosed by both Takayasu arteritis and malignant fibrous histiocytoma, from which we learned not only clinical lessons, but also consensus of relationships between these two diseases. PMID:21969061

  3. Proton therapy for the treatment of children with CNS malignancies.

    PubMed

    Sreeraman, Radhika; Indelicato, Daniel J

    2014-03-01

    Proton therapy is a novel technique for treating pediatric malignancies. As a tool to reduce normal-tissue dose, it has the potential to decrease late toxicity. Although proton therapy has been used for over five decades, most pediatric dosimetry studies and clinical series have been published over the last 10 years. The purpose of this article is to review the physical, radiobiological and economic rationales for proton therapy in pediatric CNS malignancies, and provide an overview of the current challenges and future direction of research and utilization of this approach. PMID:25055020

  4. Large malignant ovarian tumors during pregnancy: two cases

    PubMed Central

    Xu, Dong; Liang, Cheng; He, Jing

    2014-01-01

    The present study reports two cases of large ovarian malignancy during pregnancy, which is very rare. The two patients were received between Nov 2012 and Feb 2013 at Gynecological and Obstetrical Department, Women’s Hospital, School of Medicine, Zhejiang University (People’s Republic of China). Both cases present tumor sized more than 20 cm, with one case of 40 cm. Both patients underwent timely cesarean section, with survival of the Child, and successful removal of the tumor. All patients showed good outcome in the follow-up period. Therefore the large ovarian malignancy during pregnancy could be well treated after careful clinical evaluation. PMID:25484595

  5. Foreign body granuloma mimicking recurrence of malignant pleural mesothelioma

    PubMed Central

    Nakasuka, Takamasa; Fujimoto, Nobukazu; Hara, Naofumi; Miyamoto, Yosuke; Yamagishi, Tomoko; Asano, Michiko; Nishi, Hideyuki; Kishimoto, Takumi

    2015-01-01

    A 72-year-old man visited our hospital due to right pleural effusion. He had worked as a welder at a shipbuilding company and had been exposed to asbestos. Cytological examination and thoracoscopic pleural biopsy yielded a diagnosis of epithelial malignant pleural mesothelioma (MPM); extrapleural pneumonectomy (EPP) was performed. Two years later, he became aware of right-back swelling that became a fist-sized mass over 2 months. Microscopy of a tissue specimen revealed no malignant cells, but did indicate foreign body granuloma. Subcutaneous lesions that develop after EPP do not necessarily result from the recurrence of MPM, but could have benign etiologies.

  6. [Effect of tolvaptan on ascites due to malignancy].

    PubMed

    Mitsuhashi, Noboru; Nemoto, Shigeyoshi; Satoh, Yutaka; Aoki, Yu; Teranaka, Ryotaro; Sasaki, Kousuke; Shimazaki, Reiri; Ueda, Atsuhiko; Nishino, Hitoe; Akiyama, Takahiro; Hosokawa, Isamu; Yoichi, Takuya; Kawamoto, Jun; Kuboki, Satoshi; Yoshitomi, Hideyuki; Kato, Atsushi; Shimizu, Yoshiaki; Ohtsuka, Masayuki; Shimizu, Hiroaki; Miyazaki, Masaru

    2015-02-01

    Ascites accompanying a malignancy is often refractory to conventional treatment with saline diuretics, making it difficult to control. We administered a new diuretic, Tolvaptan, to 10 individuals with malignancy and heart failure accompanied by ascites, which was refractory to saline diuretics, and assessed its efficacy and adverse events. We observed a significant reduction in abdominal distension following 2 weeks of Tolvaptan administration. However, we also observed significant increases in serum potassium, urea nitrogen, and creatinine levels, but no serious adverse events. This suggests that Tolvaptan may also be effective as treatment for ascites. PMID:25743139

  7. Effect of Price Increase of Adrenocorticotropic Hormone on Treatment Practices of Infantile Spasms

    PubMed Central

    Wray, Carter D.; Benke, Timothy A.

    2011-01-01

    Intramuscular adrenocorticotropic hormone putatively constitutes the most efficacious treatment for infantile spasms. Adrenocorticotropic hormone in the United States is an “orphan drug,” made by a single manufacturer. The price of adrenocorticotropic hormone increased almost 14-fold on August 27, 2007. We sought to evaluate the impact of this price increase on treatment practices at our institution, using a retrospective chart review of all children with infantile spasms treated during 2007-2009. We identified 97 patients whose spasms were treated using antiepileptic drugs, and we determined the length of stay for those hospitalized to initiate adrenocorticotropic hormone. Patients before the price increase were more likely to have been treated with adrenocorticotropic hormone as first medication, and were hospitalized 2.2 ± 0.5 S.D. days for initiation. Patients after the price increase were more likely to have been treated initially with oral antiepileptic drugs rather than adrenocorticotropic hormone (P < 0.002). Those commencing adrenocorticotropic hormone after the price increase were hospitalized significantly longer (5.1 ± 0.6 days S.D., P < 0.001). Treatment choices need to be evidence-based, but other factors often influence them. PMID:20691936

  8. Disturbed calcium and phosphate homeostasis during treatment with ACTH of infantile spasms.

    PubMed Central

    Riikonen, R; Simell, O; Jääskeläinen, J; Rapola, J; Perheentupa, J

    1986-01-01

    Kidney histology of five infants who died during or immediately after treatment with adrenocorticotrophic hormone (ACTH) showed severe tubular and interstitial calcinosis. We therefore studied serum concentrations of calcium, inorganic phosphate, and parathormone, serum activities of alkaline phosphatase, and urinary excretion of calcium, inorganic phosphate, and cyclic adenosine monophosphate (cAMP) in 16 other children with infantile spasms before, during, and after 6 weeks of treatment with ACTH. During the treatment the following observations were made: hypocalcaemia developed in three infants; the mean daily urinary excretion of calcium in the group increased threefold and seven infants had hypercalciuria; the excretion of phosphate increased but its tubular reabsorption remained stable; and in most infants serum parathormone and urinary cAMP excretion increased, and in four infants they increased to supranormal concentrations. These biochemical changes were reversible in most infants. Radiographs suggested loss of bone mass by 3-4 weeks of treatment, with rapid recovery after treatment. We conclude that infants treated with ACTH for infantile spasms are at risk of suffering disturbance in calcium and phosphate homeostasis, which leads to nephrocalcinosis. Images Fig. 1 PMID:3017235

  9. Comprehensive functional characterization of murine infantile Batten disease including Parkinson-like behavior and dopaminergic markers

    PubMed Central

    Dearborn, Joshua T.; Harmon, Steven K.; Fowler, Stephen C.; O’Malley, Karen L.; Taylor, George T.; Sands, Mark S.; Wozniak, David F.

    2015-01-01

    Infantile neuronal ceroid lipofuscinosis (INCL, Infantile Batten disease) is a neurodegenerative lysosomal storage disease caused by a deficiency in palmitoyl protein thioesterase-1 (PPT1). The PPT1-deficient mouse (Cln1?/?) is a useful phenocopy of human INCL. Cln1?/? mice display retinal dysfunction, seizures, motor deficits, and die at ~8 months of age. However, little is known about the cognitive and behavioral functions of Cln1?/? mice during disease progression. In the present study, younger (~1–2 months of age) Cln1?/? mice showed minor deficits in motor/sensorimotor functions while older (~5–6 months of age) Cln1?/? mice exhibited more severe impairments, including decreased locomotor activity, inferior cued water maze performance, decreased running wheel ability, and altered auditory cue conditioning. Unexpectedly, certain cognitive functions such as some learning and memory capabilities seemed intact in older Cln1?/? mice. Younger and older Cln1?/? mice presented with walking initiation defects, gait abnormalities, and slowed movements, which are analogous to some symptoms reported in INCL and parkinsonism. However, there was no evidence of alterations in dopaminergic markers in Cln1?/? mice. Results from this study demonstrate quantifiable changes in behavioral functions during progression of murine INCL and suggest that Parkinson-like motor/sensorimotor deficits in Cln1?/? mice are not mediated by dopamine deficiency. PMID:26238334

  10. Early-infantile galactosialidosis: Clinical, biochemical, and molecular observations in a new patient

    SciTech Connect

    Zammarchi, E.; Donati, M.A.; Morrone, A.

    1996-08-23

    Few patients with the early-infantile form of galactosialidosis have been described to date. Presented here is the first Italian case. Fetal hydrops was detected by ultrasound at week 24 of gestation. At birth, the infant presented with hypotonial, massive edema, a flattened coarse facies. telangiectasias, and hepatosplenomegaly, but no dysostosis multiplex. The patient died 72 days postpartum. Excessive sialyloligosaccharides in urine, as well as vacuolation of lymphocytes and eosinophilic granulocytes in peripheral blood, were indicative of a lysosomal storage disease. In the patient`s fibroblasts, both {alpha}-neuraminidase and {beta}-galactosidase activities were severely reduced, and cathepsin A activity was <1% of control levels, confirming the biochemical diagnosis of galactosialidosis. However, in contrast to previously reported early-infantile cases, a normal amount of protective protein/cathepsin A mRNA was detected on Northern blots. This mutant transcript was translated into a precursor protein that was not processed into the mature enzyme and lacked both protective and catalytic activities. 28 refs., 4 figs., 1 tab.

  11. Characterization of Endothelial Microparticles Induced by Different Therapeutic Drugs for Infantile Hemangioma.

    PubMed

    Zhu, Jun-Yi; Zhang, Wei; Ren, Jian-Gang; Chen, Gang; Zhao, Yi-Fang

    2015-09-01

    Endothelial microparticles (EMPs) are complex vesicular structures with great significance in vascular pathophysiology. Here, we aimed to determine the impact of therapeutic drugs for infantile hemangioma, a common vascular tumor of infancy, on the biochemical features of EMPs. We exposed human umbilical vein endothelial cells to propranolol (Pro), dexamethasone (Dex), or rapamycin (Rap). Compared with controls, Pro and Rap dramatically augmented EMP release, whereas Dex significantly suppressed EMP generation. Drug-stimulated EMPs could inherit but tended to lose specific endothelial surface antigens from their parental cells. On the one hand, markedly distinct messenger RNA expression patterns were observed within and between drug-stimulated endothelial cells and derived EMPs. On the other hand, Rap-treated endothelial cells and Pro-induced EMPs displayed downregulation of multiple angiogenesis-related molecules at messenger RNA level compared with corresponding controls. Meanwhile, among tested angiogenesis-associated microRNAs, twelve microRNAs were downregulated in drug-induced EMPs, whereas only let-7b and miR-133a were markedly upregulated. Collectively, these data may indicate selective and distinctive package of biomolecules into EMPs depending on specific drugs. Our findings may provide novel insights into the underlying mechanisms of pharmacological therapy for infantile hemangioma. PMID:26348824

  12. Orthosis Effects on the Gait of a Child with Infantile Tibia Vara

    PubMed Central

    Alsancak, Serap

    2015-01-01

    Infantile tibia vara (ITV) is an acquired form of tibial deformity associated with tibial varus and internal torsion. As there is currently insufficient data available on the effects of orthotics on gait parameters, this study aimed to document the influence of orthosis on walking. A male infant with bilateral tibia vara used orthoses for five months. Gait evaluations were performed pre- and posttreatment for both legs. The kinematic parameters were collected by using a motion analysis system. The orthotic design principle was used to correct the femur and tibia. Posttreatment gait parameters were improved compared to pretreatment parameters. After 5 months, there was remarkable change in the stance-phase degrees of frontal plane hip joint abduction and knee joint varus. We found that orthoses were an effective treatment for the infantile tibia vara gait characteristics in this patient. Full-time use of single, upright knee-ankle-foot orthosis with a drop lock knee joint and application of corrective forces at five points along the full length of the limb were effective. PMID:26078903

  13. Orthosis Effects on the Gait of a Child with Infantile Tibia Vara.

    PubMed

    Alsancak, Serap; Guner, Senem

    2015-01-01

    Infantile tibia vara (ITV) is an acquired form of tibial deformity associated with tibial varus and internal torsion. As there is currently insufficient data available on the effects of orthotics on gait parameters, this study aimed to document the influence of orthosis on walking. A male infant with bilateral tibia vara used orthoses for five months. Gait evaluations were performed pre- and posttreatment for both legs. The kinematic parameters were collected by using a motion analysis system. The orthotic design principle was used to correct the femur and tibia. Posttreatment gait parameters were improved compared to pretreatment parameters. After 5 months, there was remarkable change in the stance-phase degrees of frontal plane hip joint abduction and knee joint varus. We found that orthoses were an effective treatment for the infantile tibia vara gait characteristics in this patient. Full-time use of single, upright knee-ankle-foot orthosis with a drop lock knee joint and application of corrective forces at five points along the full length of the limb were effective. PMID:26078903

  14. Sun exposure related methylation in malignant and non-malignant skin lesions.

    PubMed

    Sathyanarayana, Ubaradka G; Moore, Angela Yen; Li, Lin; Padar, Asha; Majmudar, Kuntal; Stastny, Victor; Makarla, Prakash; Suzuki, Makoto; Minna, John D; Feng, Ziding; Gazdar, Adi F

    2007-01-01

    We investigated the aberrant promoter methylation status of 12 genes in skin lesions, both malignant (basal cell carcinomas (BCCs), n=68 and squamous cell carcinomas (SCCs), n=35) and non-malignant (tags, n=58) skin lesions and compared the results of lesions from sun exposed (SE) and sun protected (SP) regions. Methylation was studied using a methylation specific PCR (MSP) and methylation of CDH1 was also measured using a semi-quantitative fluorescence based real-time MSP method. The methylation index (MI) was calculated as the methylated fraction of the genes examined. In this report, we found high frequencies of methylation of several known or suspected tumor suppressor genes in tags and skin cancers. Among the 12 genes, for the cadherin genes CDH1 and CDH3 and for two of the laminin 5 encoding genes LAMA3 and LAMC2 methylation frequencies greater than 30% were noted in one or more specimen types. We investigated whether methylation was tumor related. Surprisingly, the differences in the methylation profile of genes among the three specimen types were modest, and the MI, indicators of overall methylation frequencies, was nearly identical. However, significant differences were noted in the frequencies of methylation among the three specimen types for the genes RASSF1A (P=0.002), CDH1 (P=0.007) and one or more of three CAD genes (P=0.02). Methylation was highly significantly related to sun exposure, and sun protected specimens had little or no methylation. As methylation of CDH1 was completely SE specific we analyzed all the skin samples using a semi-quantitative real-time PCR assay for the CDH1 gene. The concordance between standard MSP and real-time MSP for all the samples (n=161) was 75% (P<0.0001). While weak signals were detected in the SP samples by real time PCR, the differences between SE and SP specimens were 148 fold for tags and 390 fold for BCCs. These differences were highly significant (P<0.0001). These findings suggest that methylation commences in UV exposed skin at a relatively early age and occurs in skin prior to the onset of recognizable preneoplastic changes. PMID:16494996

  15. Fractures in Individuals with and without a History of Infantile Autism. A Danish Register Study Based on Hospital Discharge Diagnoses

    ERIC Educational Resources Information Center

    Mouridsen, Svend Erik; Rich, Bente; Isager, Torben

    2012-01-01

    We compared the prevalence and types of fractures in a clinical sample of 118 individuals diagnosed as children with infantile autism (IA) with 336 matched controls from the general population. All participants were screened through the nationwide Danish National Hospital Register. The average observation time was 30.3 years (range 27.3-30.4…

  16. Genetic defect in CYP24A1, the vitamin D 24-hydroxylase gene, in a patient with severe infantile hypercalcemia

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Idiopathic infantile hypercalcemia (IIH) is a disorder the genetic etiology and physiological basis of which are not well understood. The objective of the study was to describe the underlying physiology and genetic cause of hypercalcemia in an infant with severe IIH and to extend these genetic findi...

  17. Epilepsy and Other Neurological Diseases in the Parents of Children with Infantile Autism. A Case Control Study

    ERIC Educational Resources Information Center

    Mouridsen, Svend Erik; Rich, Bente; Isager, Torben

    2008-01-01

    In order to study the broader phenotype of infantile autism (IA) we compared the rates and types of epilepsy and other neurological diseases in the parents of 111 consecutively admitted patients with IA with a matched control group of parents of 330 children from the general population. All participants were screened through the nationwide Danish…

  18. Expression of p63 in potentially malignant and malignant oral lesions

    PubMed Central

    Sinha, Anju; Chandra, Shaleen; Raj, Vineet; Zaidi, Iram; Saxena, Shikha; Dwivedi, Ruby

    2015-01-01

    Background p63, a member of p53 family, known to be expressed in embryonic tissues and basal regenerative layers of many epithelial tissues in the adult, is also expressed in various benign and malignant lesions of body including lesions of oral cavity. To evaluate the expression of p63 and compare the expression qualitatively and quantitatively in normal buccal mucosa, epithelial dysplasia, oral submucous fibrosis (OSMF), and oral squamous cell carcinoma (OSCC). Methods The study material consisted of 45 archival cases which were divided into Group I with 5 cases of normal buccal mucosa, Group II with 15 cases of epithelial dysplasia, and Group III with 10 cases of OSMF and 15 cases of OSCC. Immunohistochemical expression of p63 was assessed by using mean, standard deviation, and analysis of variance. Results Overexpression of p63 was seen in epithelial dysplasia, OSMF, and squamous cell carcinoma with an increased suprabasal expression in cases of epithelial dysplasia. The mean labeling index (LI) of p63 was found to be in increasing order from normal oral mucosa (33.75%), OSMF (57.37%), epithelial dysplasia (63.87%) to squamous cell carcinoma (69.76%). Conclusion The results suggest a possible role of p63 in oral carcinogenesis, and an increased LI as well as increased suprabasal expression of this gene in dysplastic lesions may have a potential to be utilized as a marker for premalignancy. PMID:26605141

  19. Prenatal corticosteroids modify glutamatergic and GABAergic synapse genomic fabric: Insights from a novel animal model of infantile spasms

    PubMed Central

    Iacobas, D.A.; Iacobas, S.; Chachua, T.; Goletiani, C.; Sidyelyeva, G.; Velíšková, J.; Velíšek, L.

    2013-01-01

    Summary Prenatal exposure to corticosteroids has long-term postnatal somatic and neurodevelopmental consequences. Animal studies indicate that corticosteroid exposure-associated alterations in the nervous system include hypothalamic function. Infants with infantile spasms, a devastating epileptic syndrome of infancy with characteristic spastic seizures, chaotic irregular waves on interictal electroencephalogram (EEG; hypsarhythmia) and mental deterioration, have decreased concentrations of adrenocorticotropic hormone (ACTH) and cortisol in cerebrospinal fluid strongly suggesting hypothalamic dysfunction. We have exploited this feature to develop a model of human infantile spasms by using repeated prenatal exposure to betamethasone and postnatal trigger of developmentally relevant spasms with N-methyl-D-aspartic acid (NMDA). The spasms triggered in prenatally primed rats are more severe compared to prenatally saline-injected ones and respond to ACTH, a treatment of choice for infantile spasms in humans. Using autoradiography and immunohistochemistry, we have identified a link between the spasms in our model and hypothalamus, especially the arcuate nucleus. Transcriptomic analysis of the arcuate nucleus after prenatal priming with betamethasone but before trigger of spasms indicates that prenatal betamethasone exposure down-regulates genes encoding several important proteins participating in glutamatergic and GABAergic transmission. Interestingly, there were significant sex-specific alterations after prenatal betamethasone in synapse-related gene expression but no such sex differences were found in prenatally saline-injected controls. A pair-wise relevance analysis revealed that, although the synapse gene expression in controls was independent of sex, these genes form topologically distinct gene fabrics in males and females and these fabrics are altered by betamethasone in a sex-specific manner. These findings may explain the sex differences in both normal behaviour and occurrence and severity of infantile spasms. Changes in transcript expression and their coordination may contribute to a molecular substrate of permanent neurodevelopmental changes (including infantile spasms) found after prenatal exposure to corticosteroids. PMID:23763471

  20. Prenatal corticosteroids modify glutamatergic and GABAergic synapse genomic fabric: insights from a novel animal model of infantile spasms.

    PubMed

    Iacobas, D A; Iacobas, S; Chachua, T; Goletiani, C; Sidyelyeva, G; Velíšková, J; Velíšek, L

    2013-11-01

    Prenatal exposure to corticosteroids has long-term postnatal somatic and neurodevelopmental consequences. Animal studies indicate that corticosteroid exposure-associated alterations in the nervous system include hypothalamic function. Infants with infantile spasms, a devastating epileptic syndrome of infancy with characteristic spastic seizures, chaotic irregular waves on interictal electroencephalogram (hypsarhythmia) and mental deterioration, have decreased concentrations of adrenocorticotrophic hormone (ACTH) and cortisol in cerebrospinal fluid, strongly suggesting hypothalamic dysfunction. We have exploited this feature to develop a model of human infantile spasms by using repeated prenatal exposure to betamethasone and a postnatal trigger of developmentally relevant spasms with NMDA. The spasms triggered in prenatally primed rats are more severe compared to prenatally saline-injected ones and respond to ACTH, a treatment of choice for infantile spasms in humans. Using autoradiography and immunohistochemistry, we have identified a link between the spasms in our model and the hypothalamus, especially the arcuate nucleus. Transcriptomic analysis of the arcuate nucleus after prenatal priming with betamethasone but before trigger of spasms indicates that prenatal betamethasone exposure down-regulates genes encoding several important proteins participating in glutamatergic and GABAergic transmission. Interestingly, there were significant sex-specific alterations after prenatal betamethasone in synapse-related gene expression but no such sex differences were found in prenatally saline-injected controls. A pairwise relevance analysis revealed that, although the synapse gene expression in controls was independent of sex, these genes form topologically distinct gene fabrics in males and females and these fabrics are altered by betamethasone in a sex-specific manner. These findings may explain the sex differences with respect to both normal behaviour and the occurrence and severity of infantile spasms. Changes in transcript expression and their coordination may contribute to a molecular substrate of permanent neurodevelopmental changes (including infantile spasms) found after prenatal exposure to corticosteroids. PMID:23763471

  1. Malignant Triton Tumors in Sisters with Clinical Neurofibromatosis Type 1

    PubMed Central

    Alina, Basnet; Sebastian, Jofre A.; Gerardo, Capo

    2015-01-01

    Malignant triton tumors (MTTs) are rare and aggressive sarcomas categorized as a subgroup of malignant peripheral nerve sheath tumors (MPNSTs). MTTs arise from Schwann cells of peripheral nerves or existing neurofibromas and have elements of rhabdomyoblastic differentiation. We report the occurrence of MTTs in two sisters. The first patient is a 36-year-old female who presented with left sided chest wall swelling. She also had clinical features consistent with neurofibromatosis type 1 (NF-1). Debulking of the mass showed high-grade malignant peripheral nerve sheath tumor with skeletal muscle differentiation (MTT). The patient was treated with ifosfamide and adriamycin along with radiation. Four years after treatment, she still has no evidence of disease recurrence. Her sister subsequently presented to us at the age of 42 with left sided lateral chest wall pain. Imaging showed a multicompartmental retroperitoneal cystic mass with left psoas involvement. The tumor was resected and, similarly to her sister, it showed high-grade malignant peripheral nerve sheath tumor with rhabdomyoblastic differentiation (MTT). The patient was started on chemotherapy and radiation as described above. PMID:26114002

  2. MINI REVIEW TUMOR REVERSION: CORRECTION OF MALIGNANT BEHAVIOR BY

    E-print Network

    Kenny, Paraic

    MINI REVIEW TUMOR REVERSION: CORRECTION OF MALIGNANT BEHAVIOR BY MICROENVIRONMENTAL CUES Paraic A that is intimately linked to, and controlled by, reciprocal signaling between the genetically altered tumor defects can revert tumor cells to a normal phenotype, both in vivo and in culture, even when the tumor

  3. CAPRINE HERPESVIRUS 2 ASSOCIATED MALIGNANT CATARRHAL FEVER IN DEER

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A presumptive histopathologic diagnosis of malignant catarrhal fever (MCF) was made in three cases of disease in Sika deer and white-tailed deer with various degrees of hair loss and skin lesions. Antibody against an epitope conserved among the MCF group viruses was detected in the serum of all dise...

  4. THE NEUROLEPTIC MALIGNANT SYNDROME : REPORT OF THREE CASES

    PubMed Central

    Sharma, R.C.; Thakur, S.; Sharma, Vijay

    1996-01-01

    Three patients, one male and two females who developed neuroleptic malignant syndrome following exposure to depot and oral neuroleptic are presented. The patients satisfied Levenson?s criteria for diagnosis. Bromocriptine and Electro Convulsive Therapy were found effective whereas trihexyphenidyl proved unsatisfactory in the treatment. All the patients recovered completely without complications. PMID:21584154

  5. Malignant catarrhal fever: understanding molecular diagnostics in context of epidemiology

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Malignant catarrhal fever (MCF) is a frequently fatal disease, primarily of ruminants, caused by a group of gammaherpesviruses. Due to complexities of pathogenesis and epidemiology in various species which are either clinically-susceptible or reservoir hosts, veterinary clinicians face significant ...

  6. Laparoscopic approach to gastrointestinal malignancies: Toward the future with caution

    PubMed Central

    Bencini, Lapo; Bernini, Marco; Farsi, Marco

    2014-01-01

    After the rapid acceptance of laparoscopy to manage multiple benign diseases arising from gastrointestinal districts, some surgeons started to treat malignancies by the same way. However, if the limits of laparoscopy for benign diseases are mainly represented by technical issues, oncologic outcomes remain the foundation of any procedures to cure malignancies. Cancerous patients represent an important group with peculiar aspects including reduced survival expectancy, worsened quality of life due to surgery itself and adjuvant therapies, and challenging psychological impact. All these issues could, potentially, receive a better management with a laparoscopic surgical approach. In order to confirm such aspects, similarly to testing the newest weapons (surgical or pharmacologic) against cancer, long-term follow-up is always recommendable to assess the real benefits in terms of overall survival, cancer-free survival and quality of life. Furthermore, it seems of crucial importance that surgeons will be correctly trained in specific oncologic principles of surgical oncology as well as in modern miniinvasive technologies. Therefore, laparoscopic treatment of gastrointestinal malignancies requires more caution and deep analysis of published evidences, as compared to those achieved for inflammatory bowel diseases, gastroesophageal reflux disease or diverticular disease. This review tries to examine the evidence available to date for the use of laparoscopy and robotics in malignancies arising from the gastrointestinal district. PMID:24587655

  7. Diagnosis of splenic rupture in malignant lymphoma using radionuclides

    SciTech Connect

    Wallace, J.C.

    1985-01-01

    The case of a 59-year-old woman with malignant lymphoma who was investigated for fever and left upper quadrant abdominal pain is presented. A combined spleen/lung scan showed marked medial displacement of an enlarged spleen and a gallium scan showed increased splenic uptake consistent with lymphomatous infiltration. The diagnosis of prior splenic rupture with subphrenic hematoma was confirmed at laparotomy.

  8. Intercellular communication in malignant pleural mesothelioma: properties of tunneling nanotubes

    PubMed Central

    Ady, Justin W.; Desir, Snider; Thayanithy, Venugopal; Vogel, Rachel I.; Moreira, André L.; Downey, Robert J.; Fong, Yuman; Manova-Todorova, Katia; Moore, Malcolm A. S.; Lou, Emil

    2014-01-01

    Malignant pleural mesothelioma is a particularly aggressive and locally invasive malignancy with a poor prognosis despite advances in understanding of cancer cell biology and development of new therapies. At the cellular level, cultured mesothelioma cells present a mesenchymal appearance and a strong capacity for local cellular invasion. One important but underexplored area of mesothelioma cell biology is intercellular communication. Our group has previously characterized in multiple histological subtypes of mesothelioma a unique cellular protrusion known as tunneling nanotubes (TnTs). TnTs are long, actin filament-based, narrow cytoplasmic extensions that are non-adherent when cultured in vitro and are capable of shuttling cellular cargo between connected cells. Our prior work confirmed the presence of nanotube structures in tumors resected from patients with human mesothelioma. In our current study, we quantified the number of TnTs/cell among various mesothelioma subtypes and normal mesothelial cells using confocal microscopic techniques. We also examined changes in TnT length over time in comparison to cell proliferation. We further examined potential approaches to the in vivo study of TnTs in animal models of cancer. We have developed novel approaches to study TnTs in aggressive solid tumor malignancies and define fundamental characteristics of TnTs in malignant mesothelioma. There is mounting evidence that TnTs play an important role in intercellular communication in mesothelioma and thus merit further investigation of their role in vivo. PMID:25400582

  9. Geographical differences in the distribution of malignant tumours*

    PubMed Central

    Chaklin, A. V.

    1962-01-01

    Malignant tumours are encountered among all races and in every type of geographical zone, but there are marked differences in different areas in the prevalence of particular forms of tumour—differences that are to a greater or lesser extent dependent on factors such as the climate and geography of the region and the habits, customs and occupations of the people. The study of these factors in relation to the occurrence of malignant tumours is of great importance in reaching an understanding of the etiology of tumours in man. In this paper the author discusses the many problems involved in the study of regional features in the prevalence of malignant tumours, with special reference to the difficulties of ensuring comparability of the data from widely differing regions and population groups. He concludes the paper with a review of some known facts regarding the distribution of malignant tumours at various sites in which he compares data obtained in surveys in the USSR with those obtained in other countries. PMID:14019866

  10. Targeted cellular ablation based on the morphology of malignant cells

    PubMed Central

    Ivey, Jill W.; Latouche, Eduardo L.; Sano, Michael B.; Rossmeisl, John H.; Davalos, Rafael V.; Verbridge, Scott S.

    2015-01-01

    Treatment of glioblastoma multiforme (GBM) is especially challenging due to a shortage of methods to preferentially target diffuse infiltrative cells, and therapy-resistant glioma stem cell populations. Here we report a physical treatment method based on electrical disruption of cells, whose action depends strongly on cellular morphology. Interestingly, numerical modeling suggests that while outer lipid bilayer disruption induced by long pulses (~100??s) is enhanced for larger cells, short pulses (~1??s) preferentially result in high fields within the cell interior, which scale in magnitude with nucleus size. Because enlarged nuclei represent a reliable indicator of malignancy, this suggested a means of preferentially targeting malignant cells. While we demonstrate killing of both normal and malignant cells using pulsed electric fields (PEFs) to treat spontaneous canine GBM, we proposed that properly tuned PEFs might provide targeted ablation based on nuclear size. Using 3D hydrogel models of normal and malignant brain tissues, which permit high-resolution interrogation during treatment testing, we confirmed that PEFs could be tuned to preferentially kill cancerous cells. Finally, we estimated the nuclear envelope electric potential disruption needed for cell death from PEFs. Our results may be useful in safely targeting the therapy-resistant cell niches that cause recurrence of GBM tumors. PMID:26596248

  11. Targeted cellular ablation based on the morphology of malignant cells.

    PubMed

    Ivey, Jill W; Latouche, Eduardo L; Sano, Michael B; Rossmeisl, John H; Davalos, Rafael V; Verbridge, Scott S

    2015-01-01

    Treatment of glioblastoma multiforme (GBM) is especially challenging due to a shortage of methods to preferentially target diffuse infiltrative cells, and therapy-resistant glioma stem cell populations. Here we report a physical treatment method based on electrical disruption of cells, whose action depends strongly on cellular morphology. Interestingly, numerical modeling suggests that while outer lipid bilayer disruption induced by long pulses (~100??s) is enhanced for larger cells, short pulses (~1??s) preferentially result in high fields within the cell interior, which scale in magnitude with nucleus size. Because enlarged nuclei represent a reliable indicator of malignancy, this suggested a means of preferentially targeting malignant cells. While we demonstrate killing of both normal and malignant cells using pulsed electric fields (PEFs) to treat spontaneous canine GBM, we proposed that properly tuned PEFs might provide targeted ablation based on nuclear size. Using 3D hydrogel models of normal and malignant brain tissues, which permit high-resolution interrogation during treatment testing, we confirmed that PEFs could be tuned to preferentially kill cancerous cells. Finally, we estimated the nuclear envelope electric potential disruption needed for cell death from PEFs. Our results may be useful in safely targeting the therapy-resistant cell niches that cause recurrence of GBM tumors. PMID:26596248

  12. Malignant melanoma of the tongue following low-dose radiation

    SciTech Connect

    Kalemeris, G.C.; Rosenfeld, L.; Gray, G.F. Jr.; Glick, A.D.

    1985-03-01

    A 47-year-old man had a spindly malignant melanoma of the tongue many years after low-dose radiation therapy for lichen planus. To our knowledge, only 12 melanomas of the tongue have been reported previously, and in none of these was radiation documented.

  13. Cyclin-dependent kinase inhibitor therapy for hematologic malignancies

    PubMed Central

    Bose, Prithviraj; Simmons, Gary L; Grant, Steven

    2014-01-01

    INTRODUCTION Cyclin-dependent kinases (CDKs) regulate cell cycle progression. Certain CDKs (e.g., CDK7, CDK9) also control cellular transcription. Consequently, CDKs represent attractive targets for anti-cancer drug development, as their aberrant expression is common in diverse malignancies, and CDK inhibition can trigger apoptosis. CDK inhibition may be particularly successful in hematologic malignancies, which are more sensitive to inhibition of cell cycling and apoptosis induction. AREAS COVERED A number of CDK inhibitors, ranging from pan-CDK inhibitors such as flavopiridol (alvocidib) to highly selective inhibitors of specific CDKs (e.g., CDK4/6), such as PD0332991, that are currently in various phases of development, are profiled in this review. Flavopiridol induces cell cycle arrest, and globally represses transcription via CDK9 inhibition. The latter may represent its major mechanism of action via down-regulation of multiple short-lived proteins. In early phase trials, flavopiridol has shown encouraging efficacy across a wide spectrum of hematologic malignancies. Early results with dinaciclib and PD0332991 also appear promising. EXPERT OPINION In general, the anti-tumor efficacy of CDK inhibitor monotherapy is modest, and rational combinations are being explored, including those involving other targeted agents. While selective CDK4/6 inhibition might be effective against certain malignancies, broad spectrum CDK inhibition will likely be required for most cancers. PMID:23647051

  14. Post-radiation cranial malignant fibrous histiocytoma studied by CT

    SciTech Connect

    Romero, F.J.; Ortega, A.; Ibarra, B.; Piqueras, J.; Rovira, M.

    1989-03-01

    A 37-year-old woman presented with a proven case of malignant fibrous histiocytoma of the skull. This is thought to be a rare complication of post-radiation to a chromophobe adenoma which was treated by radiotherapy nine years previously. The radiation dose given to the sella region after the removal of the chromophobe adenoma was 4500 cGy.

  15. DIAGNOSTIC FINDINGS IN PIGS WITH PORCINE MALIGNANT CATARRHAL FEVER

    Technology Transfer Automated Retrieval System (TEKTRAN)

    For the first time Ovine Herpesvirus 2 (OvHV-2) was identified in Swiss pigs as the causative agent of Porcine Malignant Catarrhal Fever (MCF). Diseased animals from two farms were observed to show weakness, anorexia, fever up to 41°C, and neurological symptoms, i.e. ataxia, convulsions and hyperest...

  16. Mutant tristetraprolin: a potent inhibitor of malignant glioma cell growth

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Malignant gliomas rely on the production of certain critical growth factors including VEGF, interleukin (IL)-6 and IL-8, to fuel rapid tumor growth, angiogenesis, and treatment resistance. Post-transcriptional regulation through adenine and uridine-rich elements of the 3' untranslated region is one ...

  17. Hyperspectral Colon Biopsy Classification into Normal and Malignant Categories

    E-print Network

    Rajpoot, Nasir

    for colon and rectal cancer) is the most common cause of death for cancers in the Western world and cure of colon cancer can be improved by efficiently clas- sifying the colon tissue cells from biopsy slides into normal and malignant classes. This report presents the classification of hyperspectral colon

  18. Endoscopic transnasal management of sinonasal malignancies – our initial experience

    PubMed Central

    Osuch-Wójcikiewicz, Ewa; Held-Zió?kowska, Marta; Ku?mi?ska, Magdalena; Niemczyk, Kazimierz

    2014-01-01

    Introduction Malignant tumors of the paranasal sinuses are traditionally managed through external approaches. Advances in endoscopic transnasal surgery have allowed for the endoscopic treatment of some of these tumors. Aim To present the results of treatment of a series of patients with paranasal sinus malignancies treated with an endoscopic approach at a single institution. Material and methods The data on tumor type, operative technique, perioperative complications and postoperative course were analyzed. Results Eleven patients meeting the inclusion criteria were identified. The histopathology was as follows: malignant melanoma in 3 patients, squamous cell carcinoma in 2, adenocarcinoma in 2, poorly differentiated carcinoma in 1, hemangiopericytoma in 1, adenoid cystic carcinoma in 1 and fibrosarcoma in 1. There were no severe perioperative complications with the exception of 1 case of cerebrospinal fluid leak, which was successfully closed. The mean observation period was 13.5 months. One of the patients died of disease, another was lost to follow-up, and one was reoperated on due to recurrence. The remaining 8 patients are alive with no signs of recurrence. Conclusions Our initial experience seems to confirm results obtained by other authors indicating that in selected cases endoscopic surgery of sinonasal malignancies is similarly effective as external approach surgery. PMID:25097677

  19. Imaging of malignancies of the biliary tract- an update

    PubMed Central

    2014-01-01

    Malignancies of the biliary tract include cholangiocarcinoma, gallbladder cancers and carcinoma of the ampulla of Vater. Biliary tract adenocarcinomas are the second most common primary hepatobiliary cancer. Due to their slow growing nature, non-specific and late symptomatology, these malignancies are often diagnosed in advanced stages with poor prognosis. Apart from incidental discovery of gall bladder carcinoma upon cholecystectomy, early stage biliary tract cancers are now detected with computed tomography (CT) and magnetic resonance imaging (MRI) with magnetic resonance cholangiopancreatography (MRCP). Accurate characterization and staging of these indolent cancers will determine outcome as majority of the patients’ are inoperable at the time of presentation. Ultrasound is useful for initial evaluation of the biliary tract and gallbladder masses and in determining the next suitable modality for further evaluation. Multimodality imaging plays an integral role in the management of the biliary tract malignancies. The imaging techniques most useful are MRI with MRCP, endoscopic retrograde cholangiopancreatography (ERCP), endoscopic ultrasound (EUS) and positron emission tomography (PET). In this review we will discuss epidemiology and the role of imaging in detection, characterization and management of the biliary tract malignancies under the three broad categories of cholangiocarcinomas (intra- and extrahepatic), gallbladder cancers and ampullary carcinomas. PMID:25608662

  20. Management of spermatic cord tumors: a rare urologic malignancy

    PubMed Central

    Rodríguez, Dayron

    2012-01-01

    Primary spermatic cord tumors are rare yet clinically significant urologic lesions that affect patients of all ages. They are the most common tumors of the paratesticular region and generally present as asymptomatic, slow growing, firm, palpable paratesticular masses. Although most of them are benign comprised primarily of lipomas, approximately 25% are potentially life-threatening malignant tumors. The most common reported malignant histological types include liposarcomas, leiomyosarcomas, rhabdomyosarcomas, malignant fibrous histiocytoma, and fibrosarcomas. Management of these malignant tumors has been difficult because of their rarity, therefore there is little consensus regarding optimal surgical and adjunctive treatment strategies. It is recommended that radiological techniques such as scrotal ultrasound (US), computed tomography, and magnetic resonance be used to evaluate these masses before surgery. The curative treatment of choice is radical orchiectomy with high cord ligation and wide excision of surrounding soft tissue structures within the inguinal canal. Patients with inadequately resected disease should undergo a reoperative procedure for wide inguinal re-resection. Retroperitoneal lymphadenectomy is recommended when there is preoperative evidence of retroperitoneal lymph node metastasis and as an adjuvant treatment for rhabdomyosarcomas since they have a higher propensity for lymphatic spread. Adjuvant treatments, such as radiotherapy and chemotherapy, have shown little efficacy, except in the management of patients with local recurrence or high-grade rhabdomyosarcomas. Long-term follow up is recommended given their high recurrence rates. PMID:23205059