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Malignant infantile osteopetrosis: case report with review of literature.  


Malignant Infantile Osteopetrosis (MIOP) is a rare genetic disorder due to osteoclast abnormal activity. We report a thirteen month-old male patient, diagnosed as MIOP while investigating the cause of hepatosplenomegaly associated with hydrocephalus. His medical history revealed non consanguineous parents and one brother's death at the same age of unknown etiology (similar symptoms). Systemic examination showed hepatosplenomegaly, growth failure, developmental milestones delay, and rickets features. Ophthalmic exam yielded bilateral optic atrophy. Skeleton radiographs detected generalized dense bone and rickets. Cerebral CT scan revealed hydrocephalus. Histological examination showed hypoplastic bone marrow and extra-medullary hematopoeisis. Diagnosis was confirmed by genetic testing that showed two heterozygote mutations within the TCIRG1 gene. The patient received supportive treatment. He died from an acute respiratory distress. MIOP should be kept in mind as a rare cause of hepatosplenomegaly. Early diagnosis and timely Hematopoietic stem cell transplantation are the only curative approach for an otherwise fatal disease. PMID:25018813

Essabar, Laila; Meskini, Toufik; Ettair, Said; Erreimi, Naima; Mouane, Nezha



Novel mutations in the a3 subunit of vacuolar H +-adenosine triphosphatase in a Japanese patient with infantile malignant osteopetrosis  

Microsoft Academic Search

A case of infantile malignant osteopetrosis is described. The patient died from respiratory hemorrhage at 7 months of age despite treatment that included high doses of active vitamin D and administration of interferon-?. A postmortem examination revealed the presence of many osteoclasts in the bone, which lacked ruffled borders. This observation was consistent with the histology of bone reported in

T Michigami; T Kageyama; K Satomura; M Shima; K Yamaoka; M Nakayama; K Ozono



Lentiviral gene transfer of TCIRG1 into peripheral blood CD34(+) cells restores osteoclast function in infantile malignant osteopetrosis.  


Infantile malignant osteopetrosis (IMO) is a rare, lethal, autosomal recessive disorder characterized by non-functional osteoclasts. More than 50% of the patients have mutations in the TCIRG1 gene, encoding for a subunit of the osteoclast proton pump. The aim of this study was to restore the resorptive function of IMO osteoclasts by lentiviral mediated gene transfer of the TCIRG1 cDNA. CD34(+) cells from peripheral blood of five IMO patients and from normal cord blood were transduced with lentiviral vectors expressing TCIRG1 and GFP under a SFFV promoter, expanded in culture and differentiated on bone slices to mature osteoclasts. qPCR analysis and western blot revealed increased mRNA and protein levels of TCIRG1, comparable to controls. Vector corrected IMO osteoclasts generated increased release of Ca(2+) and bone degradation product CTX-I into the media as well as increased formation of resorption pits in the bone slices, while non-corrected IMO osteoclasts failed to resorb bone. Resorption was approximately 70-80% of that of osteoclasts generated from cord blood. Furthermore, transduced CD34(+) cells successfully engrafted in NSG-mice. In conclusion we provide the first evidence of lentiviral-mediated correction of a human genetic disease affecting the osteoclastic lineage. PMID:23907031

Moscatelli, Ilana; Thudium, Christian Schneider; Flores, Carmen; Schulz, Ansgar; Askmyr, Maria; Gudmann, Natasja Stæhr; Andersen, Nanna Merete; Porras, Oscar; Karsdal, Morten Asser; Villa, Anna; Fasth, Anders; Henriksen, Kim; Richter, Johan



Novel mutations in the a3 subunit of vacuolar H(+)-adenosine triphosphatase in a Japanese patient with infantile malignant osteopetrosis.  


A case of infantile malignant osteopetrosis is described. The patient died from respiratory hemorrhage at 7 months of age despite treatment that included high doses of active vitamin D and administration of interferon-gamma. A postmortem examination revealed the presence of many osteoclasts in the bone, which lacked ruffled borders. This observation was consistent with the histology of bone reported in Atp6i-knockout mice, which lack the gene encoding the a3 subunit of vacuolar-type H(+)-adenosine triphosphatase (ATPase). Sequence analysis of the TCIRG1 gene encoding the a3 subunit revealed two novel mutations: a deletion/insertion mutation in exon 9 and a T-to-C transition at the splice donor site of intron 19. The former mutation caused a frame shift and premature stop codon. The latter was associated with abnormal splicing, which was confirmed by sequencing the products amplified by reverse transcription-polymerase chain reaction (RT-PCR), using total RNA from the liver specimen as template. Although several mutations in the TCIRG1 gene in infantile malignant osteopetrosis have been reported in other populations, this is the first case of a Japanese patient with a mutation identified in this gene. These results support the important role of the subunit in the function of the proton pump. PMID:11856654

Michigami, T; Kageyama, T; Satomura, K; Shima, M; Yamaoka, K; Nakayama, M; Ozono, K




PubMed Central

Osteopetrosis ("marble bone disease") is a descriptive term that refers to a group of rare, heritable disorders of the skeleton characterized by increased bone density on radiographs. The overall incidence of these conditions is difficult to estimate but autosomal recessive osteopetrosis (ARO) has an incidence of 1 in 250,000 births, and autosomal dominant osteopetrosis (ADO) has an incidence of 1 in 20,000 births. Osteopetrotic conditions vary greatly in their presentation and severity, ranging from neonatal onset with life-threatening complications such as bone marrow failure (e.g. classic or "malignant" ARO), to the incidental finding of osteopetrosis on radiographs (e.g. osteopoikilosis). Classic ARO is characterised by fractures, short stature, compressive neuropathies, hypocalcaemia with attendant tetanic seizures, and life-threatening pancytopaenia. The presence of primary neurodegeneration, mental retardation, skin and immune system involvement, or renal tubular acidosis may point to rarer osteopetrosis variants, whereas onset of primarily skeletal manifestations such as fractures and osteomyelitis in late childhood or adolescence is typical of ADO. Osteopetrosis is caused by failure of osteoclast development or function and mutations in at least 10 genes have been identified as causative in humans, accounting for 70% of all cases. These conditions can be inherited as autosomal recessive, dominant or X-linked traits with the most severe forms being autosomal recessive. Diagnosis is largely based on clinical and radiographic evaluation, confirmed by gene testing where applicable, and paves the way to understanding natural history, specific treatment where available, counselling regarding recurrence risks, and prenatal diagnosis in severe forms. Treatment of osteopetrotic conditions is largely symptomatic, although haematopoietic stem cell transplantation is employed for the most severe forms associated with bone marrow failure and currently offers the best chance of longer-term survival in this group. The severe infantile forms of osteopetrosis are associated with diminished life expectancy, with most untreated children dying in the first decade as a complication of bone marrow suppression. Life expectancy in the adult onset forms is normal. It is anticipated that further understanding of the molecular pathogenesis of these conditions will reveal new targets for pharmacotherapy.

Stark, Zornitza; Savarirayan, Ravi



Osteomyelitis of the mandible secondary to infantile osteopetrosis: a case report.  


A case of infantile malignant osteopetrosis with refractory mandibular osteomyelitis is reported. A female child was diagnosed with osteopetrosis at 2 years 8 months of age, and was scheduled to receive a bone marrow transplantation (BMT) in a pediatric department at 3 years 11 months of age. Her lower incisors were extracted at a dental clinic, after which she had recurring abscesses with progressive severity. She was referred to our department to control local infections before the BMT and was diagnosed with chronic mandibular osteomyelitis caused by osteopetrosis. Sequestrotomy and curettage were performed under general anesthesia. After surgery, daily saline irrigation was continued and osteomyelitis was well controlled. An uneventful BMT was performed, although it was refused and failed. A second BMT was planned, but during chemotherapy, cellulitis occurred after a recurrence of osteomyelitis caused by a newly erupted tooth. The local infection was controlled, but pneumonia recurred. She ultimately died of respiratory failure at 5 years of age. PMID:19464639

Yamada, Tomohiro; Mishima, Katsuaki; Imura, Hideto; Ueno, Takaaki; Matsumura, Tatsushi; Moritani, Norifumi; Sugahara, Toshio



Association of Infantile Neuroaxonal Dystrophy and Osteopetrosis: A Rare Autosomal Recessive Disorder  

Microsoft Academic Search

The association of neuroaxonal dystrophy and osteopetrosis is reported in 2 siblings born to non-consanguineous parents. The 1 st child was diagnosed as having infantile osteopetrosis shortly after delivery. A computed tomography scan of the head revealed agenesis of the corpus callosum. She died at the age of 9 months. Post-mortem examination showed pneumonia and bony sclerosis. Neuropathological examination revealed

Henrike Rees; Lee-Cyn Ang; Robin Casey; David H. George





A 15 years old Bangladeshi boy presented with hepatosplenomegaly, anaemia, multiple fractures (symptomatic and asymptomatic) without jaundice was investigated. Laboratory findings revealed leukoerythroblastic blood picture with reduced haemoglobin (7.7 gm/dl). Skeletal survey showed generalized increased bone density, sclerosed medulary space, Rugger-Jersey spine and diploic space filled with dense materials. Overlapping clinical features of both intermediate autosomal recessive and adult autosomal dominant variety of osteopetrosis were found in this patient but diagnosis were made on the basis of typical radiological finding which was mostly consistent with the adult autosomal dominant variety. The patient was treated conservatively and specialist consultation was taken in managing bony abnormalities. This patient was discharged with advised of subsequent follow-up. PMID:22081195

Khan, M N; Datta, P K; Hasan, M I; Hossain, M A; Patwary, K H; Ferdous, J



Brain lipid composition in grey-lethal mutant mouse characterized by severe malignant osteopetrosis  

Microsoft Academic Search

The grey-lethal mouse (gl\\/gl) mutant most closely resembles the severe human malignant autosomal recessive OSTM1-dependent form of osteopetrosis that\\u000a it has been described to be associated with neurological abnormalities. For this reason, we have analyzed the brain lipid\\u000a composition (gangliosides, neutral glycosphingolipids, phospholipids and cholesterol), from gl\\/gl mice at different ages of development and compared with wild type mice. Both

Alessandro Prinetti; Federica Rocchetta; Elvira Costantino; Annalisa Frattini; Elena Caldana; Francesca Rucci; Arianna Bettiga; Pietro L. Poliani; Vanna Chigorno; Sandro Sonnino



Osteopetrosis; a report of two Iranian patients with autosomal recessive inheritance pattern.  


In the rare hereditary bone disorder of osteopetrosis, reduced bone resorption function leads to both the development of densely sclerotic fragile bones and progressive obliteration of the marrow spaces and cranial foramina. Marrow obliteration, typically associated with extramedullary hemopoiesis and hepatosplenomegaly, results in anemia and thrombocytopenia; and nerve entrapment accounts for progressive blindness and hearing loss. Severe infantile or malignant osteopetrosis is the worst type of the disease which has poor prognosis. In this study we report two cases of severe infantile or malignant type of the disease in an Iranian family. Our two patients were children of a family where the wife is a grandchild of the husband's aunt. The first patient had episodes of seizure and spastic in extremities 2 weeks after birth. Gradually, the patient showed upper and lower respiratory problems and horizontal nystagmus. X-Ray of hand and foot showed widening and increased bone density and physical examination showed hepatosplenomegallay and petechiae in extremities. The patient expired due to cardiopulmonary arrest. The second patient had also episodes of seizure 2 weeks after birth. Gradually, dissymmetry in eyes appeared and blindness was confirmed by ophthalmologist. Finally the patient expired because of severe pneumonia. Autosomal recessive osteopetrosis has been reported in most ethnic groups although it is more frequently seen in ethnic groups where consanguinity is common. We report for the first time two cases of severe infantile or malignant type of the disease in an Iranian family. PMID:24551774

Morovvati, Saeid; Amirpour Amraii, Sara; Zahed Shekar Abi, Hosna; Shahbazi, Nastaran; Ranjbar, Reza



Demonstration of an osteoblast defect in two cases of human malignant osteopetrosis. Correction of the phenotype after bone marrow transplant.  

PubMed Central

Osteopetrosis is an inherited disorder characterized by bone sclerosis due to reduced bone resorption. Here we report that human osteopetrotic osteoblast-like (Ob) cells express a defective phenotype in primary cultures in vitro, and that bone marrow transplant (BMT) corrects osteoblast function. DNA analysis at polymorphic short-tandem repeat loci from donor, recipient, and primary Ob-like cells pre-BMT and 2 yr post-BMT revealed that Ob were still of recipient origin post-BMT. Osteopetrotic Ob-like cells obtained pre-BMT showed normal and abnormal 1,25(OH)2D3-induced alkaline phosphatase (ALPase) and osteocalcin production, respectively, and failed to produce macrophage colony-stimulating factor (M-CSF) in response to IL-1a and TNF-alpha. These parameters were all normalized in primary Ob-like cells prepared 2 yr post-BMT. X-linked clonality analysis at the human androgen receptor (HUMARA) locus revealed that osteoblasts showed a polyclonal and an oligoclonal derivation pre- and post-BMT respectively, indicating that a limited number of progenitor reconstituted this population. Because osteoblasts were still of recipient origin post-BMT, this suggests that functional osteoclasts, due to the replacement of hematopoeitic cells, provided a local microenvironment in vivo triggering the differentiation and/or recruitment of a limited number of functional osteoblasts.

Lajeunesse, D; Busque, L; Menard, P; Brunette, M G; Bonny, Y



Genetics Home Reference: Osteopetrosis  


... of osteopetrosis, which are usually distinguished by their pattern of inheritance: autosomal dominant, autosomal recessive, or X- ... either an autosomal dominant or an autosomal recessive pattern of inheritance. The signs and symptoms of this ...


Clinicoradiological Findings of Benign Osteopetrosis: Report of Two New Cases  

PubMed Central

Osteopetrosis represents a heterogeneous group of rare, hereditary bone dysplasias that share the hallmark of increased bone density caused by osteoclast dysfunction. It can manifest through a spectrum of symptoms and severity, from neonatal onset with life-threatening complications ("malignant" autosomal recessive osteopetrosis) to two more benign conditions with the incidental radiographic findings, principally affecting adults (autosomal dominant osteopetrosis type I and type II). We report 2 new cases of autosomal dominant osteopetrosis type II. Both subjects were short in stature. Multiple healed fractures of long bones, diminished marrow spaces and hypoplastic maxillary sinuses were remarkable findings. To our knowledge they are the first reported cases of autosomal dominant type II of this disease in Iran.

Tohidi, Elahe; Bagherpour, Ali



Osteopetrosis Mutation R444L Causes Endoplasmic Reticulum Retention and Misprocessing of Vacuolar H+-ATPase a3 Subunit*  

PubMed Central

Osteopetrosis is a genetic bone disease characterized by increased bone density and fragility. The R444L missense mutation in the human V-ATPase a3 subunit (TCIRG1) is one of several known mutations in a3 and other proteins that can cause this disease. The autosomal recessive R444L mutation results in a particularly malignant form of infantile osteopetrosis that is lethal in infancy, or early childhood. We have studied this mutation using the pMSCV retroviral vector system to integrate the cDNA construct for green fluorescent protein (GFP)-fused a3R445L mutant protein into the RAW 264.7 mouse osteoclast differentiation model. In comparison with wild-type a3, the mutant glycoprotein localized to the ER instead of lysosomes and its oligosaccharide moiety was misprocessed, suggesting inability of the core-glycosylated glycoprotein to traffic to the Golgi. Reduced steady-state expression of the mutant protein, in comparison with wild type, suggested that the former was being degraded, likely through the endoplasmic reticulum-associated degradation pathway. In differentiated osteoclasts, a3R445L was found to degrade at an increased rate over the course of osteoclastogenesis. Limited proteolysis studies suggested that the R445L mutation alters mouse a3 protein conformation. Together, these data suggest that Arg-445 plays a role in protein folding, or stability, and that infantile malignant osteopetrosis caused by the R444L mutation in the human V-ATPase a3 subunit is another member of the growing class of protein folding diseases. This may have implications for early-intervention treatment, using protein rescue strategies.

Bhargava, Ajay; Voronov, Irina; Wang, Yongqiang; Glogauer, Michael; Kartner, Norbert; Manolson, Morris F.



Osteopetrosis mutation R444L causes endoplasmic reticulum retention and misprocessing of vacuolar H+-ATPase a3 subunit.  


Osteopetrosis is a genetic bone disease characterized by increased bone density and fragility. The R444L missense mutation in the human V-ATPase a3 subunit (TCIRG1) is one of several known mutations in a3 and other proteins that can cause this disease. The autosomal recessive R444L mutation results in a particularly malignant form of infantile osteopetrosis that is lethal in infancy, or early childhood. We have studied this mutation using the pMSCV retroviral vector system to integrate the cDNA construct for green fluorescent protein (GFP)-fused a3(R445L) mutant protein into the RAW 264.7 mouse osteoclast differentiation model. In comparison with wild-type a3, the mutant glycoprotein localized to the ER instead of lysosomes and its oligosaccharide moiety was misprocessed, suggesting inability of the core-glycosylated glycoprotein to traffic to the Golgi. Reduced steady-state expression of the mutant protein, in comparison with wild type, suggested that the former was being degraded, likely through the endoplasmic reticulum-associated degradation pathway. In differentiated osteoclasts, a3(R445L) was found to degrade at an increased rate over the course of osteoclastogenesis. Limited proteolysis studies suggested that the R445L mutation alters mouse a3 protein conformation. Together, these data suggest that Arg-445 plays a role in protein folding, or stability, and that infantile malignant osteopetrosis caused by the R444L mutation in the human V-ATPase a3 subunit is another member of the growing class of protein folding diseases. This may have implications for early-intervention treatment, using protein rescue strategies. PMID:22685294

Bhargava, Ajay; Voronov, Irina; Wang, Yongqiang; Glogauer, Michael; Kartner, Norbert; Manolson, Morris F



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


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

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



A novel missense mutation in the CLCN7 gene linked to benign autosomal dominant osteopetrosis: a case series  

PubMed Central

Introduction Osteopetrosis is a rare inherited genetic disease characterized by sclerosis of the skeleton. The absence or malfunction of osteoclasts is found to be strongly associated with the disease evolution. Currently, four clinically distinct forms of the disease have been recognized: the infantile autosomal recessive osteopetrosis, the malignant and the intermediate forms, and autosomal dominant osteopetrosis, type I and type II forms. The autosomal recessive types are the most severe forms with symptoms in very early childhood, whereas the autosomal dominant classes exhibit a heterogeneous trait with milder symptoms, often at later childhood or adulthood. Case presentation Case 1 is the 12-year-old daughter (index patient) of an Iraqi-Kurdish family who, at the age of eight years, was diagnosed clinically to have mild autosomal dominant osteopetrosis. Presently, at 12-years old, she has severe complications due to the disease progression. In addition, the same family previously experienced the death of a female child in her late childhood. The deceased child had been misdiagnosed, at that time, with thalassemia major. In this report, we extended our investigation to identify the type of the inheritance patterns of osteopetrosis using molecular techniques, because consanguineous marriages exist within the family history. We have detected one heterozygous mutation in exon 15 of the Chloride Channel 7 gene in the index patient (Case 1), whereas other mutations were not detected in the associated genes TCIRG1, OSTM1, RANK, and RANKL. The missense mutation (CGG>TGG) located in exon 15 (c.1225C>T) of the Chloride Channel 7 gene changed the amino acid position 409 from arginine to tryptophan (p.R409W, c.1225C>T). Case 2 is the 16-year-old son (brother of the index patient) of the same family who was diagnosed clinically with mild autosomal dominant osteopetrosis. We have identified the same heterozygous mutation in exon 15 of the Chloride channel 7 gene in this patient (Case 2). The missense mutation (CGG>TGG) located in exon 15 (c.1225C>T) of the Chloride channel 7 gene changed the amino acid position 409 from arginine to tryptophan (p.R409W, c.1225C>T). In addition to the clinical diagnosis of both cases, the missense mutation we identified in one allele of the Chloride channel 7 gene could be linked to autosomal dominant osteopetrosis-II because the symptoms appear in late childhood or adolescence. Conclusion In this family, the molecular diagnosis was confirmed after identification of the same mutation in the older son (sibling). Furthermore, we detected that the father and his brother (the uncle) are carriers of the same mutation, whereas the mother and her sister (the aunt) do not carry any mutation of the Chloride channel 7 gene. Thus, the disease penetrance is at least 60% in the family. The mother and father are cousins and a further consanguineous marriage between the aunt and the uncle is not recommended because the dominant allele of the Chloride channel 7 gene will be transferred to the progeny. However, a similar risk is also expected following a marriage between the uncle and an unrelated woman. The p.R409W mutation in the Chloride channel 7 gene has not yet been described in the literature and it possibly has a dominant-negative impact on the protein.



Genetic analysis of autosomal recessive osteopetrosis in Chuvashiya: the unique splice site mutation in TCIRG1 gene spread by the founder effect  

Microsoft Academic Search

The rare malignant disorder autosomal recessive osteopetrosis (OPTB) is one of the most prevalent autosomal recessive diseases in the Chuvash Republic of Russia. The purpose of this study was to determine the underlying molecular cause of osteopetrosis in Chuvashiya and to reveal the factors causing the unusual high frequency of the disease in this region. Having assumed a founder effect,

Elena A Bliznetz; Svetlana M Tverskaya; Rena A Zinchenko; Anna V Abrukova; Ekaterina N Savaskina; Maxim V Nikulin; Alexander G Kirillov; Evgeny K Ginter; Alexander V Polyakov



Desmoplastic infantile astrocytoma: recurrence with malignant transformation into glioblastoma: a case report.  


Desmoplastic infantile astrocytoma (DIA) is an uncommon brain tumor of early infancy. The tumor is characterized by a lobar location, glial histology, and excellent prognosis after surgical removal. DIA and a similar tumor, desmoplastic infantile ganglioglioma (DIG) have been considered to be benign neoplasms, but the prognosis of DIA and DIG is currently under question as atypical and aggressive clinical features of the tumors have been reported. We encountered a patient who was diagnosed with DIA at the age of 22 months and exhibited tumor recurrence 8 years later. Surgical removal of the recurred tumor revealed that the tumor had transformed to overt glioblastoma. This case demonstrates that DIA is not an absolutely benign tumor and that careful clinical surveillance is needed during the follow-up period. PMID:21947035

Phi, Ji Hoon; Koh, Eun Jung; Kim, Seung-Ki; Park, Sung-Hye; Cho, Byung-Kyu; Wang, Kyu-Chang



Exome sequencing identifies CTSK mutations in patients originally diagnosed as intermediate osteopetrosis.  


Autosomal Recessive Osteopetrosis is a genetic disorder characterized by increased bone density due to lack of resorption by the osteoclasts. Genetic studies have widely unraveled the molecular basis of the most severe forms, while cases of intermediate severity are more difficult to characterize, probably because of a large heterogeneity. Here, we describe the use of exome sequencing in the molecular diagnosis of 2 siblings initially thought to be affected by "intermediate osteopetrosis", which identified a homozygous mutation in the CTSK gene. Prompted by this finding, we tested by Sanger sequencing 25 additional patients addressed to us for recessive osteopetrosis and found CTSK mutations in 4 of them. In retrospect, their clinical and radiographic features were found to be compatible with, but not typical for, Pycnodysostosis. We sought to identify modifier genes that might have played a role in the clinical manifestation of the disease in these patients, but our results were not informative. In conclusion, we underline the difficulties of differential diagnosis in some patients whose clinical appearance does not fit the classical malignant or benign picture and recommend that CTSK gene be included in the molecular diagnosis of high bone density conditions. PMID:24269275

Pangrazio, Alessandra; Puddu, Alessandro; Oppo, Manuela; Valentini, Maria; Zammataro, Luca; Vellodi, Ashok; Gener, Blanca; Llano-Rivas, Isabel; Raza, Jamal; Atta, Irum; Vezzoni, Paolo; Superti-Furga, Andrea; Villa, Anna; Sobacchi, Cristina



Exome sequencing identifies CTSK mutations in patients originally diagnosed as intermediate osteopetrosis?  

PubMed Central

Autosomal Recessive Osteopetrosis is a genetic disorder characterized by increased bone density due to lack of resorption by the osteoclasts. Genetic studies have widely unraveled the molecular basis of the most severe forms, while cases of intermediate severity are more difficult to characterize, probably because of a large heterogeneity. Here, we describe the use of exome sequencing in the molecular diagnosis of 2 siblings initially thought to be affected by “intermediate osteopetrosis”, which identified a homozygous mutation in the CTSK gene. Prompted by this finding, we tested by Sanger sequencing 25 additional patients addressed to us for recessive osteopetrosis and found CTSK mutations in 4 of them. In retrospect, their clinical and radiographic features were found to be compatible with, but not typical for, Pycnodysostosis. We sought to identify modifier genes that might have played a role in the clinical manifestation of the disease in these patients, but our results were not informative. In conclusion, we underline the difficulties of differential diagnosis in some patients whose clinical appearance does not fit the classical malignant or benign picture and recommend that CTSK gene be included in the molecular diagnosis of high bone density conditions.

Pangrazio, Alessandra; Puddu, Alessandro; Oppo, Manuela; Valentini, Maria; Zammataro, Luca; Vellodi, Ashok; Gener, Blanca; Llano-Rivas, Isabel; Raza, Jamal; Atta, Irum; Vezzoni, Paolo; Superti-Furga, Andrea; Villa, Anna; Sobacchi, Cristina



When bone becomes marble: Head and neck manifestations of osteopetrosis  

PubMed Central

Osteopetrosis is a genetically determined bone disease resulting from malfunction of osteoclastic activity, leading to excessive deposition of immature bone. This may result in complete agenesis of the paranasal sinuses, oral complications and multiple cranial neuropathies. The case of a 12-year-old boy with osteopetrosis is presented.

Hamdan, Abdul-Latif H; Nabulsi, Mona M; Farhat, Firas T; Haidar, Rashid K; Fuleihan, Nabil S



Oligodontia associated with osteopetrosis: a rare case report.  


Osteopetrosis is a descriptive term that refers to a group of rare hereditary disorders of the skeleton characterized by increased density of the bones. It was first described in 1904 by Albers-Schonberg, a German radiologist. This disease varies greatly in its presentation and severity ranging from neonatal onset with life threatening conditions such as bone marrow failure to incidental finding of osteopetrosis on radiographs. Dental abnormality may be attributed to pathological changes in the bone. Dentists should be aware of patients with the disease because of its effect on osteoclast function which results in impaired wound healing. This paper presents the case of a five-year-old girl exhibiting oligodontia associated with osteopetrosis. PMID:22041010

Vinay, C; Uloopi, K S; Rao, R Chandrasekhar; Kumar, R Santosh; Madhuri, V



Optic nerve decompression for osteopetrosis in early childhood.  


Visual failure in osteopetrosis may result from retinal degeneration or compression of the optic nerve in the narrowed optic canals. We report the evaluation and treatment of five children with osteopetrosis whose optic nerve dysfunction seems to have been related to the latter etiology. Evaluation of visual function was carried out by means of behavioral observation and flash visual evoked responses. Of six nerves evaluated both pre- and postoperatively, the visual evoked responses seemed to improve in four. Three nerves were serially evaluated without an operation, and one showed changes consistent with maturation. One nerve was evaluated with serial postoperative evoked potentials and showed no change. We conclude that surgical decompression of the optic nerve in patients with documented optic nerve dysfunction and osteopetrosis allows improvement in visual function and is, therefore, an important consideration in the evaluation and management of patients with this disease. PMID:3200377

Haines, S J; Erickson, D L; Wirtschafter, J D



Centrifugal osteopetrosis: appendicular sclerosis with relative sparing of the vertebrae  

Microsoft Academic Search

A previously unreported pattern of bone involvement in autosomal dominant osteopetrosis is described in three affected members\\u000a of a Vietnamese kindred. The hands, feet, distal bones, and skull were markedly osteosclerotic on radiologic examination.\\u000a The vertebrae displayed very minimal thickening of the endplates in two of the cases, and no visible involvement in the third.\\u000a The vertebral bone density (assessed

Christopher S. Kovacs; Robert G. W. Lambert; Guy J. Lavoie; Kerry Siminoski



A homozygous contiguous gene deletion in chromosome 16p13.3 leads to autosomal recessive osteopetrosis in a Jordanian patient.  


Human malignant autosomal recessive osteopetrosis (ARO) is a genetically heterogeneous disorder caused by reduced bone resorption by osteoclasts. Mutations in the CLCN7 gene are responsible not only for a substantial portion of ARO patients but also for other forms of osteopetrosis characterized by different severity and inheritance. The lack of a clear genotype/phenotype correlation makes genetic counseling a tricky issue for CLCN7-dependent osteopetrosis. Here, we characterize the first homozygous interstitial deletion in 16p13.3, detected by array comparative genomic hybridization in an ARO patient of Jordanian origin. The deletion involved other genes besides CLCN7, while the proband displayed a classic ARO phenotype; however, her early death did not allow more extensive clinical investigations. The identification of this novel genomic deletion involving a large part of the CLCN7 gene is of clinical relevance, especially in prenatal diagnosis, and suggests the possibility that this kind of mutation has been underestimated so far. These data highlight the need for alternative approaches to genetic analysis also in other ARO-causative genes. PMID:22847576

Pangrazio, Alessandra; Frattini, Annalisa; Valli, Roberto; Maserati, Emanuela; Susani, Lucia; Vezzoni, Paolo; Villa, Anna; Al-Herz, Waleed; Sobacchi, Cristina



Mild osteopetrosis in the microphthalmia-oak ridge mouse. A model for intermediate autosomal recessive osteopetrosis in humans.  

PubMed Central

Mutations at the mouse microphthalmia (mi) locus affect coat color, eye development, and mast cells. The original allele, mi, also shows severe osteopetrosis. Mice homozygous for the microphthalmia-Oak Ridge (Mior) mutation are white, microphthalmic animals with retarded incisor development. To investigate whether this mutation causes osteopetrosis, we examined skeletal tissues of the Mior mouse. A typical osteopetrotic lesion, accumulation of unresorbed primary spongiosa, was found at the metaphyses of long bones and at the costochondral junctions in Mior/Mior mice from 10 days to 37 days of age, whereas no accumulation was seen at the mid-diaphyses in these bones. The osteopetrotic conditions of Mior/Mior mice increased progressively during the first 5 weeks after birth. However, adult Mior/Mior mice 3 months or older showed improvement of the osteopetrotic condition, although the disease was not completely resolved. Ultrastructurally, osteoclasts of Mior/Mior mice had well developed ruffled borders. These results show that the Mior mutation has milder osteopetrotic changes than the original mi mutation, a surprising observation given that both mutations affect the same functional domain of the mi protein, a basic-Helix-Loop-Helix-Zipper transcription factor. The Mior phenotype resembles the intermediate autosomal recessive osteopetrosis in humans. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9

Nii, A.; Steingrimsson, E.; Copeland, N. G.; Jenkins, N. A.; Ward, J. M.



Autosomal dominant osteopetrosis revisited: lessons from recent studies.  


Systematic studies of autosomal dominant osteopetrosis (ADO) were followed by the identification of underlying mutations giving unique possibilities to perform translational studies. What was previously designated ADO1 turned out to be a high bone mass phenotype caused by a missense mutation in the first propeller of LRP5, a region of importance for binding inhibitory proteins. Thereby, ADO1 cannot be regarded as a classical form of osteopetrosis but must now be considered a disease of LRP5 activation. ADO (Albers-Schönberg disease, or previously ADO2) is characterized by increased number of osteoclasts and a defect in the chloride transport system (ClC-7) of importance for acidification of the resorption lacuna (a form of Chloride Channel 7 Deficiency Osteopetrosis). Ex vivo studies of osteoclasts from ADO have shown that cells do form normally but have reduced resorption capacity and an expanded life span. Bone formation seems normal despite decreased osteoclast function. Uncoupling of formation from resorption makes ADO of interest for new strategies for treatment of osteoporosis. Recent studies have integrated bone metabolism in whole-body energy homeostasis. Patients with ADO may have decreased insulin levels indicating importance beyond bone metabolism. There seems to be a paradigm shift in the treatment of osteoporosis. Targeting ClC-7 might introduce a new principle of dual action. Drugs affecting ClC-7 could be antiresorptive, still allowing ongoing bone formation. Inversely, drugs affecting the inhibitory site of LRP5 might stimulate bone formation and inhibit resorption. Thereby, these studies have highlighted several intriguing treatment possibilities, employing novel modes of action, which could provide benefits to the treatment of osteoporosis. PMID:23744590

Bollerslev, Jens; Henriksen, Kim; Nielsen, Morten Frost; Brixen, Kim; Van Hul, Wim



A prosthetic management technique for osteopetrosis affecting the maxilla.  


Bony anatomical anomalies can complicate the construction and successful wearing of removable prostheses. Osteopetrosis is a group of diseases that affect the growth and continuous remodelling of bone which in turn can result in gross irregular alveolar bone morphology. This paper describes the management of a patient with this problem and emphasises the challenges in constructing a successful complete maxillary removable prosthesis. The utilisation of a flexible base plate material as an alternative to traditional materials will be highlighted. Irregular bony morphology is a recognised potential obstacle to the successful construction of removable prostheses. In most cases the problem can be overcome but in extreme and less common circumstances, management of these features can be more problematic. This paper describes a technique used to manage extreme alveolar irregularity which may perhaps be applied to those problems more commonly encountered in every day clinical practice but are less extreme then those described in this paper. PMID:17645071

Dewan, Karun; Bishop, Karl; Hollisey-Mclean, David




PubMed Central

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.



Desmoplastic Infantile Ganglioglioma  


... Stages and Grades Treatment Options About Clinical Trials Latest Research Coping with Side Effects After Treatment Questions to ... Childhood - About Clinical Trials Desmoplastic Infantile Ganglioglioma - Childhood - Latest Research Desmoplastic Infantile Ganglioglioma - Childhood - Coping with Side Effects ...


MT2013-31:Allo BMT for Metabolic Disorders, Osteopetrosis and Males With Rett Syndrome

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; Rett Syndrome; Sphingolipidosis; Gangliosidosis; Globoid Cell Leukodystrophy; Metachromatic Leukodystrophy; Niemann Pick B; Niemann Pick C Subtype 2; I-cell Disease



The syndrome of osteopetrosis, renal acidosis and cerebral calcification in two sisters.  


The syndrome of osteopetrosis associated with renal tubular acidosis and cerebral calcification, inherited as an autosomal recessive disorder, as seen in two sisters, is described. The primary defect in this rare syndrome is deficiency of carbonic anhydrase (CA) II. Significant reduction in blood levels of CA II were found in both parents and another sister, suggesting that these individuals are heterozygotic carriers. PMID:3221988

Al Rajeh, S; el Mouzan, M I; Ahlberg, A; Ozaksoy, D



Bone marrow transplantation corrects osteopetrosis in the carbonic anhydrase II deficiency syndrome  

Microsoft Academic Search

Carbonic anhydrase II (CAII), found in renal tubules, brain, and osteoclasts, is critical in acid-base homeostasis and bone remodeling. Deficiency of CAII gives rise to a syndrome of osteopetrosis, renal tubular acidosis (RTA), and cerebral calci- fication with associated developmental delay. It is inherited in an autosomal reces- sive fashion and found most frequently in the Mediterranean region and the

Corrina McMahon; Andrew Will; Peiyi Hu; Gul N. Shah; William S. Sly; Owen P. Smith



Genetic analysis of autosomal recessive osteopetrosis in Chuvashiya: the unique splice site mutation in TCIRG1 gene spread by the founder effect.  


The rare malignant disorder autosomal recessive osteopetrosis (OPTB) is one of the most prevalent autosomal recessive diseases in the Chuvash Republic of Russia. The purpose of this study was to determine the underlying molecular cause of osteopetrosis in Chuvashiya and to reveal the factors causing the unusual high frequency of the disease in this region. Having assumed a founder effect, we performed linkage disequilibrium (LD) mapping of the OPTB locus at the TCIRG1 region and found a unique splice site mutation c.807+5G>A in all Chuvashian OPTB patients studied. We then analyzed the mutational change in mRNA and detected an intron insertion within the mutant transcript, resulting in a frameshift and premature stop-codon formation (p.Leu271AspfsX231). A decreased expression of the mutant transcript was also detected, which may have been the result of nonsense-mediated decay. Real-time qPCR and MLPA melting curve analysis-based systems were designed and used for c.807+5G>A mutation screening. In addition to analyzing the gene frequency in Chuvashiya, we also estimated three other populations in the Volga-Ural region (Mari, Udmurt and Bashkir). We found a 1.68% prevalence in Chuvashiya (calculated disease frequency, 1/3500 newborns) and a 0.84% in the Mari population (1/14 000 newborns). The haplotype analysis revealed that all OPTB cases in Chuvashians and Marians originated from a single mutational event and the age of the mutation in Chuvashians was estimated to be approximately 890 years. PMID:19172990

Bliznetz, Elena A; Tverskaya, Svetlana M; Zinchenko, Rena A; Abrukova, Anna V; Savaskina, Ekaterina N; Nikulin, Maxim V; Kirillov, Alexander G; Ginter, Evgeny K; Polyakov, Alexander V



Involvement of PLEKHM1 in osteoclastic vesicular transport and osteopetrosis in incisors absent rats and humans  

PubMed Central

This study illustrates that Plekhm1 is an essential protein for bone resorption, as loss-of-function mutations were found to underlie the osteopetrotic phenotype of the incisors absent rat as well as an intermediate type of human osteopetrosis. Electron and confocal microscopic analysis demonstrated that monocytes from a patient homozygous for the mutation differentiated into osteoclasts normally, but when cultured on dentine discs, the osteoclasts failed to form ruffled borders and showed little evidence of bone resorption. The presence of both RUN and pleckstrin homology domains suggests that Plekhm1 may be linked to small GTPase signaling. We found that Plekhm1 colocalized with Rab7 to late endosomal/lysosomal vesicles in HEK293 and osteoclast-like cells, an effect that was dependent on the prenylation of Rab7. In conclusion, we believe PLEKHM1 to be a novel gene implicated in the development of osteopetrosis, with a putative critical function in vesicular transport in the osteoclast.

Van Wesenbeeck, Liesbeth; Odgren, Paul R.; Coxon, Fraser P.; Frattini, Annalisa; Moens, Pierre; Perdu, Bram; MacKay, Carole A.; Van Hul, Els; Timmermans, Jean-Pierre; Vanhoenacker, Filip; Jacobs, Ruben; Peruzzi, Barbara; Teti, Anna; Helfrich, Miep H.; Rogers, Michael J.; Villa, Anna; Van Hul, Wim



The murine mutation osteopetrosis is in the coding region of the macrophage colony stimulating factor gene  

Microsoft Academic Search

MICE homozygous for the recessive mutation osteopetrosis (op) on chromosome 3 have a restricted capacity for bone remodelling, and are severely deficient in mature macrophages and osteoclasts1-3. Both cell populations originate from a common haemopoietic progenitor. As op\\/op mice are not cured by transplants of normal bone marrow cells4, the defects in op\\/op mice may be associated with an abnormal

Hisahiro Yoshida; Shin-Ichi Hayashi; Takahiro Kunisada; Minetaro Ogawa; Satomi Nishikawa; Hitoshi Okamura; Tetsuo Sudo; Leonard D. Shultz; Shin-Ichi Nishikawa



Loss of the ClC7 Chloride Channel Leads to Osteopetrosis in Mice and Man  

Microsoft Academic Search

Chloride channels play important roles in the plasma membrane and in intracellular organelles. Mice deficient for the ubiquitously expressed ClC-7 Cl? channel show severe osteopetrosis and retinal degeneration. Although osteoclasts are present in normal numbers, they fail to resorb bone because they cannot acidify the extracellular resorption lacuna. ClC-7 resides in late endosomal and lysosomal compartments. In osteoclasts, it is

Uwe Kornak; Dagmar Kasper; Michael R Bösl; Edelgard Kaiser; Michaela Schweizer; Ansgar Schulz; Wilhelm Friedrich; Günter Delling; Thomas J Jentsch



Unexplained anaemia and failure to thrive as initial symptoms of infantile choriocarcinoma: a review  

Microsoft Academic Search

Infantile choriocarcinoma is a highly malignant germ cell tumour sub-entity thought to originate from the placenta. The aim of this review is to alert clinicians to clinical symptoms and course of neonatal\\/infantile choriocarcinoma in order to improve the prognosis of affected children by early diagnosis and appropriate treatment. The clinical details of all 30 cases according to a Medline literature

Martin E. G. Blohm; Ulrich Göbel



A new modality of treatment for non-united fracture of the humerus in a patient with osteopetrosis: a case report  

Microsoft Academic Search

INTRODUCTION: Osteopetrosis introduces technical limitations to the traditional treatment of fracture management that may be minimised with specific pre-operative planning. Extreme care and caution are required when drilling, reaming, or inserting implants in patients with osteopetrosis. Caution must be exercised throughout the postoperative course when these patients are at greatest risk for device failure or further injury. CASE PRESENTATION: We

Imran Rafiq; Amit Kapoor; David JC Burton; John F Haines



Histidinemia and Infantile Autism  

ERIC Educational Resources Information Center

The article presents a case history of a boy with both infantile autism and histidenia (an inborn error of amino acid metabolism), and discusses the possible relationship between the two conditions. (DLS)

Kotsopoulos, S.; Kutty, K. M.



Instantánea del cáncer infantil

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.


Hypohidrotic Ectodermal Dysplasia, Osteopetrosis, Lymphedema, and Immunodeficiency in an Infant with Multiple Opportunistic Infections.  


Osteopetrosis, lymphedema, hypohidrotic ectodermal dysplasia, and immunodeficiency (OL-HED-ID) is a rare X-linked disorder with only three reported prior cases in the English-language literature. We describe a case of OL-HED-ID in a male infant who initially presented with congenital lymphedema, leukocytosis, and thrombocytopenia of unknown etiology at 7 days of age. He subsequently developed gram-negative sepsis and multiple opportunistic infections including high-level cytomegalovirus viremia and Pneumocystis jiroveci pneumonia. The infant was noted to have mildly xerotic skin, fine sparse hair, and periorbital wrinkling, all features suggestive of ectodermal dysplasia. Skeletal imaging showed findings consistent with osteopetrosis, and immunologic investigation revealed hypogammaglobulinemia and mixed T- and B-cell dysfunction. Genetic testing revealed a novel mutation in the nuclear factor kappa beta (NF-KB) essential modulator (NEMO) gene, confirming the diagnosis of OL-HED-ID. Mutations in the NEMO gene have been reported in association with hypohidrotic ectodermal dysplasia with immunodeficiency (HED-ID), OL-HED-ID, and incontinentia pigmenti. In this case, we report a novel mutation in the NEMO gene associated with OL-HED-ID. This article highlights the dermatologic manifestations of a rare disorder, OL-HED-ID, and underscores the importance of early recognition and prompt intervention to prevent life-threatening infections. PMID:23405946

Carlberg, Valerie M; Lofgren, Sabra M; Mann, Julianne A; Austin, Jared P; Nolt, Dawn; Shereck, Evan B; Davila-Saldana, Blachy; Zonana, Jonathan; Krol, Alfons L



RANK-Dependent Autosomal Recessive Osteopetrosis: Characterization of Five New Cases With Novel Mutations  

PubMed Central

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. © 2012 American Society for Bone and Mineral Research

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



High and Low Dose OPG-Fc Cause Osteopetrosis-Like Changes in Infant Mice  

PubMed Central

Background Receptor Activator of Nuclear Factor-?B ligand (RANKL) inhibitors are being considered for use in children with osteogenesis imperfecta (OI). We sought to assess efficacy of two doses of a RANKL inhibitor, OPG-Fc, in a growing animal model of OI, the col1?2-deficient mouse (oim/oim) and its wildtype controls (+/+). Methods Treated mice showed runting and radiographic evidence of osteopetrosis with either high (20 mg/kg twice weekly) or low dose (1 mg/kg/week) OPG-Fc. Because of this adverse event, OPG-Fc treatment was halted and the mice were euthanized or monitored for recovery with monthly radiographs and assessment of serum osteoclast activity (TRACP-5b) until 25 weeks of age. Results Twelve weeks of OPG-Fc treatment resulted in radiographic and histologic osteopetrosis with no evidence of bone modeling and negative Tartrate-resistant acid phosphatase (TRAP) staining, root dentin abnormalities, and TRACP-5b activity suppression. Signs of recovery appeared four to eight weeks post-treatment cessation. Conclusion Both high and low dose OPG-Fc treatment resulted in osteopetrotic changes in infant mice, an outcome not seen in studies with the RANKL inhibitor RANK – Immunoglobulin Fc segment complex (RANK-Fc), or in studies with older animals. Further investigations of RANKL inhibitors prior to their consideration for use in children are necessary.

Bargman, Renee; Posham, Ram; Boskey, Adele; Carter, Erin; DiCarlo, Edward; Verdelis, Kostas; Raggio, Cathleen; Pleshko, Nancy



Update on infantile hemangiomas.  


Infantile hemangiomas are the most common tumors of infancy. The serendipitous discovery of the therapeutic efficacy of propranolol in the management of infantile hemangiomas has revolutionized the care and understanding of these lesions, and greatly improved the prognosis for a good cosmetic outcome. In addition, there has been an expansion of indications for treatment of hemangiomas, taking into account not only those hemangiomas that can cause airway compromise, amblyopia, and cardiac overload, but also those lesions that can lead to unsatisfactory cosmetic outcome or deformity after involution. Current concepts of pathogenesis of infantile hemangiomas, of segmental hemangiomas with systemic associations, of hepatic hemangiomas, and of the use of systemic and topical beta-blockers for the management of IH are all reviewed. PMID:23419763

Lee, Kachiu C; Bercovitch, Lionel



Giant infantile pulmonary hemangioma.  


We present a very unusual case of giant infantile pulmonary hemangioma presenting as a large solitary pulmonary mass. This was successfully managed with surgical resection. Histological examination revealed that the mass was positive for GLUT-1 receptor, a marker for infantile hemangioma. To our knowledge only a few cases of pulmonary hemangioma have been described previously in the literature. Pulmonary hemangiomas are very rare lesions, most of them presenting as a pulmonary mass. This case emphasizes the fact that this rare lesion should be considered in the differential of an enhancing pulmonary mass in an infant. PMID:20461368

Pandya, Rajul; Tummala, Venkat



Infantile systemic hyalinosis.  


Infantile systemic hyalinosis is a rare disorder characterized by widespread deposition of hyaline. They usually present with skin lesions, joint contractures, and intractable diarrhea. We report a 2 year 4 month old boy with growth retardation, typical facial appearance, gingival enlargement, generalized stiff skin, joint contractures, and intermittent diarrhea. Skin biopsy revealed deposition of hyaline. PMID:22318104

Giri, Prabhas Prasun; Raushan, Rajesh; Ghosh, Apurba; Pal, Priyankar



Progressive Infantile Axonal Polyneuropathy  

Microsoft Academic Search

Polyneuropathies are relatively uncommon in early infancy and the majority of affected children are found to have hypomyelinating neuropathies. Axonal sensorimotor neuropathies have been described in childhood but the majority of affected children present at or after 6 months of age, have nonprogressive courses, and achieve the ability to walk, albeit late. Here we present three infants with infantile progressive

Thomas J. Geller; Anne M. Connolly; Suresh Kotagal; Arthur L. Prensky



Hyperlexia in Infantile Autism.  

ERIC Educational Resources Information Center

Followup of 20 boys (from 7-17 years old) diagnosed with infantile autism revealed Ss' compulsion to decode written materials without comprehension of its meaning. Major differences in intelligence and verbal and nonverbal abilities were noted. It is suggested that the presence of hyperlexia may identify a subgroup of autistic children. (Author/CL)

Whitehouse, Dennis; Harris, James C.



Infantile glaucoma: electrophysiology.  


Thirty-eight children with congenital infantile glaucoma (hydrophthalmia) were examined using electrophysiological methods. In contrast with adult glaucoma, hydrophthalmia is characterized by early changes in the electro-retinogram and rise of the threshold of electrical phosphene, which points to serious pathological changes in the retinal optic nerve. In such cases surgical intervention is indicated. PMID:525287

Khvatova, A V; Kovalchuk, N A; Bogoslovsky, A I



Differential diagnosis of infantile hemangiomas.  


1.Compare and contrast infantile hemangiomas with other vascular anomalies that may be confused clinically.2.Describe the vascular anomalies classification system according to the International Society for the Study of Vascular Anomalies (ISSVA), highlighting the differences between vascular tumors, such as infantile hemangiomas, and vascular malformations.3.Briefly review associated signs or syndromes found in the context of certain vascular anomalies.Infantile hemangiomas are the most common benign vascular tumor in infancy but may mimic many other types of vascular anomalies. In many cases, the appearance, time of onset, growth pattern, and consistency of infantile hemangiomas make the diagnosis straightforward (see "Pathogenesis of Infantile Hemangiomas" on p. 321). However, many other vascular lesions can appear quite similar to infantile hemangiomas, especially early in life, and at times this makes the correct diagnosis challenging. PMID:22881414

Perman, Marissa J; Castelo-Soccio, Leslie; Jen, Melinda



A new osteopetrosis mutant mouse strain (ntl) with odontoma-like proliferations and lack of tooth roots  

PubMed Central

A new spontaneous mouse mutant (ntl) with autosomal-recessive osteopetrosis was characterized. These mice formed tartrate-resistant acid phosphate (TRAP)-positive osteoclasts but their osteoclasts had no ruffled border and did not resorb bone. These mice displayed no tooth eruption or tooth root formation. Adult mutant mice developed odontoma-like proliferations near the proximal ends of the incisors. Intraperitoneal injection of progenitor cells from the liver of 16.5 days postcoitum wild-type embryos into newborn mutants rescued the osteopetrosis phenotype, indicating that the defects were intrinsic to the osteoclasts. Our findings not only provide further support for a critical role of osteoclasts in tooth eruption and tooth root development, but also suggest that the perturbation of the homeostasis of the odontogenic precursors of the incisors is primarily responsible for the development of the odontoma-like proliferations in this osteopetrosis mutant. Genetic mapping has narrowed down the location of the mutant allele to a genetic interval of 3.2 cM on mouse chromosome 17.

Lu, Xincheng; Rios, Hector F.; Jiang, Baichun; Xing, Lianping; Kadlcek, Renata; Greenfield, Edward M.; Luo, Guangbin; Feng, Jian Q.



Social Class and Infantile Autism.  

ERIC Educational Resources Information Center

Twenty infantile autistic children (mean age 10.6 years) were compared with 50 seven-year-old Swedish children with regard to social class. The distributions of social class were almost identical in the infantile autism group and in the random group. (Author/SW)

Gillberg, Christopher; Schaumann, Helen



Infantile hemangiomas: A review  

PubMed Central

Infantile hemangiomas (IH) are the most common eyelid and orbital tumors of childhood. Although they are considered benign lesions that have a generally self-limited course, in the periocular region, they have the potential to cause amblyopia, strabismus, and severe disfigurement. The decision for treatment can be a source of anxiety for patients, parents, and physicians alike. There are numerous treatment modalities, including emerging therapies that may make treatment safer and more effective than ever before. This review discusses our current understanding of this disease, its management, and future therapies.

Callahan, Alison B.; Yoon, Michael K.



Intracranial infantile hemangiopericytoma.  


Intracranial infantile hemangiopericytomas (HPCs) are exceedingly rare lesions. Only 11 cases have been previously reported in the literature. As such, little is known about the etiology, long-term prognosis, and optimal treatment paradigm. Clinically, they are consistently less aggressive than those in adults. The authors present the case of a 2-month-old boy with an intracranial HPC, review the available literature, discuss the evolving concepts of what defines an HPC, and offer a potential explanation to how HPC histology might relate to the clinical behavior of these lesions. PMID:24905842

McHugh, Brian J; Baranoski, Jacob F; Malhotra, Ajay; Vortmeyer, Alexander O; Sze, Gordon; Duncan, Charles C



Mice lacking tartrate-resistant acid phosphatase (Acp 5) have disrupted endochondral ossification and mild osteopetrosis.  


Mature osteoclasts specifically express the purple, band 5 isozyme (Acp 5) of tartrate-resistant acid phosphatase, a binuclear metalloenzyme that can generate reactive oxygen species. The function of Acp 5 was investigated by targeted disruption of the gene in mice. Animals homozygous for the null Acp 5 allele had progressive foreshortening and deformity of the long bones and axial skeleton but apparently normal tooth eruption and skull plate development, indicating a rôle for Acp 5 in endochondral ossification. Histomorphometry and mineralization density analysis of backscattered electron imaging revealed widened and disorganized epiphyseal growth plates with delayed mineralization of cartilage in 6- to 8-week-old mutant mice. The membrane bones of the skull showed increased density at all ages examined, indicating defective osteoclastic bone turnover. Increased mineralization density was observed in the long bones of older animals which showed modelling deformities at their extremities: heterozygotes and homozygous Acp 5 mutant mice had tissue that was more mineralized and occupied a greater proportion of the bone in all regions. Thus the findings reflect a mild osteopetrosis due to an intrinsic defect of osteoclastic modelling activity that was confirmed in the resorption pit assay in vitro. We conclude that this bifunctional metalloprotein of the osteoclast is required for normal mineralization of cartilage in developing bones; it also maintains integrity and turnover of the adult skeleton by a critical contribution to bone matrix resorption. PMID:8898228

Hayman, A R; Jones, S J; Boyde, A; Foster, D; Colledge, W H; Carlton, M B; Evans, M J; Cox, T M



Two Cases of Infantile Intra-abdominal Inflammatory Myofibroblastic Tumor  

PubMed Central

Inflammatory myofibroblastic tumor (IMT) is rare mesenchymal solid tumor that consists of proliferating myofibroblasts with an inflammatory infiltrate background. It has a very low prevalence in infants and occurs mainly in children and young adults. IMT are mainly located in the thoracic cavity, but intra-abdominal lesions are rare. IMT can exhibit locally aggressive neoplastic processes and metastases similar to malignancies, so, have clinical importance. Herein, we describe two infantile intra-abdominal IMT cases presenting with incidentally found palpable abdominal mass. A 4-month-old male infant had IMT at the ileal mesentery and a 5-month-old male infant had IMT at liver. Both cases were successfully treated by complete surgical resection without complication or recurrence. Considering the biological behavior of the intermediate type of neoplasm in IMT, we expect good survivals when achieving appropriate surgical resection without adjuvant therapy in infantile intra-abdominal IMT.

Kim, Soo-Hong; Kim, Hae Young



Higher osteoclastic demineralization and highly mineralized cement lines with osteocalcin deposition in a mandibular cortical bone of autosomal dominant osteopetrosis type II: ultrastructural and undecalcified histological investigations  

Microsoft Academic Search

In this study we report on histological and ultrastructural investigations of the mandibular cortical bone in a case of autosomal dominant osteopetrosis type II complicated by mandibular osteomyelitis. Histologically, there was a marked increase in the number and size of osteoclasts on the inner bone surface. An undecalcified preparation showed a pair of deeply stained (highly demineralized) and stain-phobic (highly

I Semba; T Ishigami; K Sugihara; M Kitano



Neonatal reductions in osteoclast number and function account for the transient nature of osteopetrosis in the rat mutation microphthalmia blanc (mib).  


We have examined the general and skeletal manifestations of osteopetrosis in a new, mild osteopetrotic mutation in the rat, microphalmia blanc (mib). Newborn mutant (mib) rats exhibit the typical skeletal deformities and sclerosis of osteopetrosis at birth, which are reduced significantly during the first postnatal month but don't disappear entirely up to 8 months later. Osteoclast numbers, staining for TRAP and TraATPase, and bone resorption are reduced in mutants during the first 2 postnatal weeks but improve by 1 month. In mutants, serum concentrations of calcium and phosphorus are normal, but 1,25(OH)2 D levels are higher at 1 week than those in normal littermates. Neonatally, mutants exhibit extramedullary hemopoiesis in the spleen. These results are interpreted to mean that the transient perinatal skeletal sclerosis in mib rats is caused by reduced production and function of osteoclasts in this period. The recent description of transient, perinatal osteopetrosis in a child suggests that analyses of the early differences between mild and severe animal mutations might distinguish those children with osteopetrosis who need treatment from those who do not. PMID:7873301

Cielinski, M J; Marks, S C



Role of RANKL (TNFSF11)-dependent osteopetrosis in the dental phenotype of Msx2 null mutant mice.  


The MSX2 homeoprotein is implicated in all aspects of craniofacial skeletal development. During postnatal growth, MSX2 is expressed in all cells involved in mineralized tissue formation and plays a role in their differentiation and function. Msx2 null (Msx2 (-/-)) mice display complex craniofacial skeleton abnormalities with bone and tooth defects. A moderate form osteopetrotic phenotype is observed, along with decreased expression of RANKL (TNFSF11), the main osteoclast-differentiating factor. In order to elucidate the role of such an osteopetrosis in the Msx2 (-/-) mouse dental phenotype, a bone resorption rescue was performed by mating Msx2 (-/-) mice with a transgenic mouse line overexpressing Rank (Tnfrsf11a). Msx2 (-/-) Rank(Tg) mice had significant improvement in the molar phenotype, while incisor epithelium defects were exacerbated in the enamel area, with formation of massive osteolytic tumors. Although compensation for RANKL loss of function could have potential as a therapy for osteopetrosis, but in Msx2 (-/-) mice, this approach via RANK overexpression in monocyte-derived lineages, amplified latent epithelial tumor development in the peculiar continuously growing incisor. PMID:24278237

Castaneda, Beatriz; Simon, Yohann; Ferbus, Didier; Robert, Benoit; Chesneau, Julie; Mueller, Christopher; Berdal, Ariane; Lézot, Frédéric



Role of RANKL (TNFSF11)-Dependent Osteopetrosis in the Dental Phenotype of Msx2 Null Mutant Mice  

PubMed Central

The MSX2 homeoprotein is implicated in all aspects of craniofacial skeletal development. During postnatal growth, MSX2 is expressed in all cells involved in mineralized tissue formation and plays a role in their differentiation and function. Msx2 null (Msx2?/?) mice display complex craniofacial skeleton abnormalities with bone and tooth defects. A moderate form osteopetrotic phenotype is observed, along with decreased expression of RANKL (TNFSF11), the main osteoclast-differentiating factor. In order to elucidate the role of such an osteopetrosis in the Msx2?/? mouse dental phenotype, a bone resorption rescue was performed by mating Msx2?/? mice with a transgenic mouse line overexpressing Rank (Tnfrsf11a). Msx2?/? RankTg mice had significant improvement in the molar phenotype, while incisor epithelium defects were exacerbated in the enamel area, with formation of massive osteolytic tumors. Although compensation for RANKL loss of function could have potential as a therapy for osteopetrosis, but in Msx2?/? mice, this approach via RANK overexpression in monocyte-derived lineages, amplified latent epithelial tumor development in the peculiar continuously growing incisor.

Castaneda, Beatriz; Simon, Yohann; Ferbus, Didier; Robert, Benoit; Chesneau, Julie; Mueller, Christopher



[Early infantile epileptic encephalopathy].  


Early infantile epileptic encephalopathy (EIEE) with burst-suppression (Ohtaharas syndrome) is a rare type of epileptic encephalopathy in infancy and represents the earliest type of age-related symptomatic generalised epilepsy. We present 4 cases of EIEE fulfilling the classic diagnostic criteria, excluding the cases with segmentary and erratic myoclonic, characteristic features of Early Myoclonic Encephalopathy. All the patients were females. Pregnancy and delivery were normal and no other cases were observed in the families. One of the patients had a normal twin brother. Seizures began in all the cases before the 10th day of life. The initial EEG showed burst-suppression pattern, lasting for an average of 2.3 months of age (1.5-4 months). Seizures were initially resistant to therapy, although 2 cases showed partial response. None of the patients evolved to West syndrome. A case died at 5 months of age. No etiologic factors were found in two cases, but hemimegalencephaly was detected in the other two patients; in one of them seizures disappeared after corticectomy. We believe EIEE constitutes a type of epileptic encephalopaty which can be distinguished from other types of early onset epilepsy and should be included in the International Classification of Epilepsies with the West and Lennox-Gastaut syndromes. PMID:7497179

Martínez Bermejo, A; Roche, C; López Martín, V; Pascual Castroviejo, I



Hyperlexia in infantile autism.  


Twenty boys meeting the current DSM III criteria for infantile autism at the time of diagnosis were found to be hyperlexic in childhood and have been followed up for 7-17 years. The most striking feature of the group was the compulsion to decode written material without comprehension of its meaning, and this constituted a behavioral phenotype for this population. On word recognition tests such as the WRAT, they scored significantly higher than would be predicted on the basis of intelligence but demonstrated severe reading retardation on tests of reading comprehension such as the Gates-McGinitie. Major differences in intelligence were detected, ranging from severe mental retardation to very superior intelligence. Major differences in verbal and nonverbal abilities were also noted. Many were found to have unusually good memory, both visual and auditory, and the majority possessed an excellent stored vocabulary that could be used with written words despite the poverty of their expressive language. It is suggested that the presence of hyperlexia may identify a subgroup of autistic children. PMID:6480546

Whitehouse, D; Harris, J C



Infantile amnesia: a neurogenic hypothesis.  


In the late 19th Century, Sigmund Freud described the phenomenon in which people are unable to recall events from early childhood as infantile amnesia. Although universally observed, infantile amnesia is a paradox; adults have surprisingly few memories of early childhood despite the seemingly exuberant learning capacity of young children. How can these findings be reconciled? The mechanisms underlying this form of amnesia are the subject of much debate. Psychological/cognitive theories assert that the ability to maintain detailed, declarative-like memories in the long term correlates with the development of language, theory of mind, and/or sense of "self." However, the finding that experimental animals also show infantile amnesia suggests that this phenomenon cannot be explained fully in purely human terms. Biological explanations of infantile amnesia suggest that protracted postnatal development of key brain regions important for memory interferes with stable long-term memory storage, yet they do not clearly specify which particular aspects of brain maturation are causally related to infantile amnesia. Here, we propose a hypothesis of infantile amnesia that focuses on one specific aspect of postnatal brain development--the continued addition of new neurons to the hippocampus. Infants (humans, nonhuman primates, and rodents) exhibit high levels of hippocampal neurogenesis and an inability to form lasting memories. Interestingly, the decline of postnatal neurogenesis levels corresponds to the emergence of the ability to form stable long-term memory. We propose that high neurogenesis levels negatively regulate the ability to form enduring memories, most likely by replacing synaptic connections in preexisting hippocampal memory circuits. PMID:22904373

Josselyn, Sheena A; Frankland, Paul W



Modeling new therapies for infantile spasms  

PubMed Central

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.

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



A novel NEMO gene mutation causing osteopetrosis, lymphoedema, hypohidrotic ectodermal dysplasia and immunodeficiency (OL-HED-ID).  


Genetic conditions are increasingly recognised as a cause of multisystem diseases in children. We report a 6-year-old boy with hypohidrotic ectodermal dysplasia, immunodeficiency, osteopetrosis and lymphoedema, associated with a novel mutation in the NF-?? essential modulator (NEMO) gene. He is the longest surviving of three reported boys with these clinical features. Hypohidrotic ectodermal dysplasia, a congenital disorder of teeth, hair and eccrine sweat glands is most commonly inherited as an X-linked recessive trait. Associated immunodeficiency (HED-ID) may give rise to serious infections in early life. Mutations in the NEMO gene give rise to a heterogeneous group of disorders, including the X-linked dominant disorder incontinentia pigmenti. This is characterised by typical skin changes leading to linear pigmentary change and variable associated features; in males, prenatal death usually occurs. Our patient, like one if the previous cases and all of their mothers, demonstrates features of incontinentia pigmenti. PMID:20499091

Roberts, Catherine M L; Angus, Janet E; Leach, Ian H; McDermott, Elizabeth M; Walker, David A; Ravenscroft, Jane C



Malignant hyperthermia.  


Malignant hyperthermia refers to covert myopathies, which do not affect the individual during daily life activities, but may lead to life-threatening tachycardia, rigor, labile blood pressure and most importantly high-grade temperature when exposed to general anaesthesia. This conditions is mimicked by thyroid storm, neuroleptic malignant syndrome, phaeochromocytoma and sepsis. We present a presumptive case of malignant hyperthermia. PMID:14764260

Nasir, Khawaja Kamal; Zafar, Ayaz-bin; Mansoor, Faraz; Mushtaq, Sadia; Ahmad, Jawad; Khan, Imran Muhammad



Genetic influences and infantile autism  

Microsoft Academic Search

IN his original description of infantile autism, Kanner suggested an ``inborn defect'', because symptoms were often present from early infancy. Despite the rarity of a family history of autism and lack of a known increase in parental consanguinity, there are two reasons for suspecting hereditary influences: the 2% rate of autism in siblings is 50 times that of the general

Susan Folstein; Michael Rutter



Genetics Home Reference: X-linked infantile nystagmus  


... PubMed Recent literature OMIM Genetic disorder catalog Conditions > X-linked infantile nystagmus On this page: Description Genetic ... names Glossary definitions Reviewed September 2009 What is X-linked infantile nystagmus? X-linked infantile nystagmus is ...


Genetics Home Reference: X-linked infantile spasm syndrome  


... PubMed Recent literature OMIM Genetic disorder catalog Conditions > X-linked infantile spasm syndrome On this page: Description ... names Glossary definitions Reviewed August 2012 What is X-linked infantile spasm syndrome? X-linked infantile spasm ...


Infantile colic, facts and fiction  

PubMed Central

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.



Malignant prolactinomas.  


Six cases of malignant prolactinoma have been reported; an additional two cases are presented here and the literature is reviewed. Diagnosis rests upon evidence of metastasis rather than histological criteria per se. Cases have arisen from known adenomas, particularly the invasive type. Bromocriptine is a useful palliative. The features and treatment of malignant prolactinoma are discussed. PMID:1870674

Popovic, E A; Vattuone, J R; Siu, K H; Busmanis, I; Pullar, M J; Dowling, J



Infantile Spasms in Children with TSC  

MedlinePLUS Videos and Cool Tools

... Efficacy of the ketogenic diet for infantile spasms. Pediatrics 109(5):780-3 Lux AL, Edwards SW, Osborne JP, Hancock E, Johnson AL, Verity CM, Kennedy CR, O'Callaghan FJ, Newton RW (2002) Randomized trial of vigabatrin in patients with infantile spasms. Neurology 59(4):648 Mackay ...


Neuroimaging findings in infantile GM1 gangliosidosis  

Microsoft Academic Search

GM1 gangliosidosis is an autosomal recessive glycosphingolipid storage disease caused by defects in the enzyme ?-galactosidase. Three clinical forms (infantile-, juvenile-, and adult-onset) of the disease are recognized. Patients with infantile GM1 gangliosidosis present at birth or shortly thereafter with somatic and bony changes, followed by severe neurological deterioration ultimately leading to death within the first 2 years of life.

Ilknur Erol; Füsun Alehan; M. Ali Pourbagher; Oguz Canan; S. Vefa Yildirim



Polysomnographic findings in infantile Pompe disease.  


Infantile Pompe disease is a rare, autosomal recessive disorder due to deficiency of the enzyme acid ?-glucosidase that degrades lysosomal glycogen. Clinical features of diffuse hypotonia, cardiomyopathy, and weakness are present within the first days to months of life in patients with classic infantile Pompe disease. Progression of the disease often leads to respiratory failure. Although sleep apnea is reported in late-onset Pompe disease, sleep pathology is not well characterized in infantile disease. In this retrospective study, we analyzed nocturnal polysomnography results from 17 patients with infantile-onset Pompe disease. Obstructive sleep apnea and hypoventilation were common among this cohort, even in those that did not have symptoms of sleep-disordered breathing. All patients with infantile-onset Pompe disease should undergo polysomnography as a routine part of their care. PMID:24123966

Kansagra, Sujay; Austin, Stephanie; DeArmey, Stephanie; Kishnani, Priya S; Kravitz, Richard M



Bone marrow necrosis preceding infantile acute lymphoblastic leukaemia.  


We report a case of bone marrow necrosis preceding infantile acute lymphoblastic leukaemia (ALL). Bone marrow necrosis is a rare antemortem event and has been known to be present in many conditions, notably in haematological malignancies like acute lymphoblastic leukaemia. This case was a 6-month-old Chinese boy who was referred to Hospital Universiti Kebangsaan Malaysia for further investigation of pancytopaenia, high-grade fever, bloody diarrhoea and petechial rashes for one week. His first bone marrow aspirate revealed bone marrow necrosis. His clinical condition improved after ten days. However, his full blood picture then revealed the presence of 5% blast cells. His subsequent marrow 2 weeks later revealed acute lymphoblastic leukaemia (FAB-L1) and immunophenotyping showed precursor B acute lymphoblastic leukaemia-null type. He was started on United Kingdom Acute Lymphoblastic leukaemia (UK ALL) Infantile Leukaemia protocol, however, he defaulted treatment after 3 days. Mode of presentation, mechanism of disease and laboratory investigations and outline of treatment will be discussed. PMID:19108404

Eusni, Rahayu Mohd Tohit; Hamidah Hussin, Noor; Zarina, Abd Latiff; Rahman, Jamal



Clinical electrophysiology of infantile botulism.  


Infantile botulism is a recently recognized cause of acute hypotonic paresis and respiratory failure in young infants. Electrophysiological testing has proven useful in early diagnosis in suspected cases by demonstrating abnormal neuromuscular transmission as is known to occur in botulism. Twenty-five infants with bacteriologically proven botulism were studied by uniform methods in our laboratory and characteristic electrophysiological abnormalities were found. Repetitive stimulation at 20 and 50 Hz was the most specific single test; 23 patients (92%) showed incremental responses. Stimulation at low rates was less specific. Concentric needle electromyography provided useful supplemental information. Short-duration, low-amplitude motor unit potentials were prominent in 22 patients (92%) accompanied by abnormal spontaneous activity in 13 patients (54%). Compound muscle action potential amplitudes were usually reduced, but motor and sensory conduction studies were otherwise normal. Electrodiagnostic testing demonstrated one or more characteristic abnormalities in all cases of infantile botulism. This constellation of electrophysiological abnormalities, combined with an appropriate clinical picture, was so distinctive as to allow early presumptive diagnosis of infant botulism, before the results of bacteriological testing were available. PMID:6312310

Cornblath, D R; Sladky, J T; Sumner, A J



[Syndrome associating: osteopetrosis, tubular acidosis, mental retardation and cerebral calcifications due to carbonic anhydrase II deficiency. Apropos of 3 cases in the siblings].  


Three new cases of a syndrome including osteopetrosis, tubular acidosis, mental retardation and cerebral calcifications are reported in the same sibship. This rare syndrome has an autosomal recessive inheritance and is due to carbonic anhydrase II deficiency. Fractures and mild sensorial manifestations were noticed in 2 cases. Mental deficiency and otitis were present in the 3 cases. Blood count and phosphocalcic metabolites were normal. A proximal tubular acidosis was present in each case. The radiological features were specific: cerebral calcifications were present in all cases since the age of 2 1/2 years; osteocondensation and bone modeling were predominant in long bones metaphyses. Alcalinization improved the height growth. PMID:1904705

Bejaoui, M; Kamoun, A; Baraket, M; Bourguiba, H; Lakhoua, R



Differentially expressed genes in autosomal dominant osteopetrosis type II osteoclasts reveal known and novel pathways for osteoclast biology.  


Autosomal dominant osteopetrosis type II (ADO II) is a rare, heritable bone disorder characterized by a high bone mass and insufficient osteoclast activity. Mutations in the CLCN7 gene have been reported to cause ADO II. To gain novel insights into the pathways dysregulated in ADOII osteoclasts, we identified changes in gene expression in osteoclasts from patients with a heterozygous mutation of CLCN7. To do this, we carried out a transcriptomic study comparing gene expression in the osteoclasts of patients with ADO II and healthy donors. Our data show that, according to our selection criteria, 182 genes were differentially expressed in osteoclasts from patients and controls. From the 18 displaying the highest change in microarray, we confirmed differential expression for seven by qPCR. Although two of them have previously been found to be expressed in osteoclasts (ITGB5 and SERPINE2), the other five (CES1 (carboxyl esterase 1), UCHL1 (ubiquitin carboxy-terminal esterase L1, also known as ubiquitin thiolesterase), WARS (tryptophanyl-tRNA synthetase), GBP4 (guanylate-binding protein 4), and PRF1) are not yet known to have a role in this cell type. At the protein level, we confirmed elevated expression of ITGB5 and reduced expression of WARS, PRF1, and SERPINE2. Transfection of ClC-7 harboring the G215R mutation into osteoclasts resulted in an increased ITGB5 and reduced PRF1 expression of borderline significance. Finally, we observed that the ADO II patients presented a normal or increased serum level of bone formation markers, demonstrating a coupling between dysfunctional osteoclasts and osteoblasts. Sphingosine kinase 1 mRNA was expressed at the same level in ADO II and control osteoclasts. In conclusion, these data suggest that in addition to an acidification dysfunction caused by the CLCN7 mutation, a change in ITGB5, PRF1, WARS, and SERPINE2 expression could be part of the osteoclastic phenotype of ADO II. PMID:24336069

Coudert, Amélie E; Del Fattore, Andrea; Baulard, Céline; Olaso, Robert; Schiltz, Corinne; Collet, Corinne; Teti, Anna; de Vernejoul, Marie-Christine



Genetics Home Reference: Infantile neuroaxonal dystrophy  


... in breaking down (metabolizing) fats called phospholipids. Phospholipid metabolism is important for many body processes, including helping ... signs and symptoms of infantile neuroaxonal dystrophy, phospholipid metabolism problems have been seen in both this disorder ...


Genetics Home Reference: Infantile systemic hyalinosis  


... Testing Registry Genetic testing PubMed Recent literature OMIM Genetic disorder catalog Conditions > Infantile systemic hyalinosis On this page: ... test information (1 link) PubMed - Recent literature OMIM - Genetic disorder catalog What other names do people use for ...


Early Infantile Autism and Autistic Psychopathy  

ERIC Educational Resources Information Center

The paper tries to assign to autistic psychopathy a definite place in psychiatric nosology and to delineate sharply the differences between the essential characteristics of it and of early infantile autism. (Author)

Van Krevelen, D. Arn



Hematologic malignancies  

SciTech Connect

The principle aim of this book is to give practical guidelines to the modern treatment of the six important hematologic malignancies. Topics considered include the treatment of the chronic leukemias; acute leukemia in adults; the myeloproliferative disorders: polycythemia vera, essential thrombocythemia, and idiopathic myelofibrosis/agnogenic myeloid metaplasia; Hodgkin's Disease; non-Hodgkin's lymphoma; and Multiple Myeloma.

Hoogstraten, B.



Genetic and biologic classification of infantile spasms.  


Infantile spasms constitute an age-dependent epilepsy, highly associated with cognitive impairment, autism, and movement disorders. Previous classification systems focused on a distinction between symptomatic and cryptogenic etiologies, and have not kept pace with 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 likelier to manifest infantile spasms, and we review the literature to propose a genetic classification of these disorders. Children demonstrating genetic associations with infantile spasms also manifest phenotypes beyond epilepsy that may be explained by recent advances in the understanding of underlying biological mechanisms. Therefore we propose a biologic classification of genes highly associated with infantile spasms, and articulate models for infantile spasms pathogenesis based on those data. The two best described pathways of pathogenesis involve abnormalities in the gene regulatory network of gamma-aminobutyric acidergic forebrain development and abnormalities in molecules expressed at the synapse. These genetic and biologic classifications are flexible, and they should encourage much needed progress in syndrome recognition, clinical genetic testing, and the development of new therapies targeting specific pathways of pathogenesis. PMID:22114996

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



A case of infantile digital fibromatosis with associated thoracic abnormalities  

Microsoft Academic Search

An adult case of infantile digital fibromatosis is presented; there were associated thoracic abnormalities; this has not been previously reported. Infantile digital fibromatosis ( =infantile dermal fibromatosis, recurring digital fibrous tumor) is a distinctive fibrous tumor of infancy which affects the fingers and toes. This disease is usually diagnosed during the first year of life.

A. Atabey; A. Barutçu; T. Canda; D. Özaksoy



Visual remapping in infantile nystagmus.  


The possibility that patients with idiopathic infantile nystagmus achieve spatial constancy by visual remapping was investigated by comparing subjective localization of flashed test targets to their absolute position in space and to their absolute position on the retina. Nystagmats first viewed a screen-stationary reference target that was followed by a test flash. A computer used eye movement feedback to precisely control the test flash position on the retina. All six nystagmats detected test flashes throughout their nystagmus cycle. For three nystagmats test flashes (total N = 48) were delivered to the same retinal locus that were, at different times, to the right and left of the reference target. More than two-thirds of such crossover stimuli were correctly located in space: when only those stimuli at least 0.5 deg from the reference were considered, two of three subjects correctly located all stimuli. Taken together these results argue that our subjects could see throughout the nystagmus cycle and shifted their visual map in synchrony with their nystagmus as an explicit means of avoiding oscillopsia. PMID:1509701

Goldstein, H P; Gottlob, I; Fendick, M G



Malignant hyperthermia.  


Malignant hyperthermia (MH) is an uncommon, life-threatening pharmacogenetic disorder of the skeletal muscle. It presents as a hypermetabolic response in susceptible individuals to potent volatile anesthetics with/without depolarizing muscle relaxants; in rare cases, to stress from exertion or heat stress. Susceptibility to malignant hyperthermia (MHS) is inherited as an autosomally dominant trait with variable expression and incomplete penetrance. It is known that the pathophysiology of MH is related to an uncontrolled rise of myoplasmic calcium, which activates biochemical processes resulting in hypermetabolism of the skeletal muscle. In most cases, defects in the ryanodine receptor are responsible for the functional changes of calcium regulation in MH, and more than 300 mutations have been identified in the RYR1 gene, located on chromosome 19q13.1. The classic signs of MH include increase of end-tidal carbon dioxide, tachycardia, skeletal muscle rigidity, tachycardia, hyperthermia and acidosis. Up to now, muscle contracture test is regarded as the gold standard for the diagnosis of MHS though molecular genetic test is used, on a limited basis so far to diagnose MHS. The mortality of MH is dramatically decreased from 70-80% to less than 5%, due to an introduction of dantrolene sodium for treatment of MH, early detection of MH episode using capnography, and the introduction of diagnostic testing for MHS. This review summarizes the clinically essential and important knowledge of MH, and presents new developments in the field. PMID:23198031

Kim, Dong-Chan



Whole-exome sequencing identifies mutations in the nucleoside transporter gene SLC29A3 in dysosteosclerosis, a form of osteopetrosis  

PubMed Central

Dysosteosclerosis (DSS) is the form of osteopetrosis distinguished by the presence of skin findings such as red-violet macular atrophy, platyspondyly and metaphyseal osteosclerosis with relative radiolucency of widened diaphyses. At the histopathological level, there is a paucity of osteoclasts when the disease presents. In two patients with DSS, we identified homozygous or compound heterozygous missense mutations in SLC29A3 by whole-exome sequencing. This gene encodes a nucleoside transporter, mutations in which cause histiocytosis–lymphadenopathy plus syndrome, a group of conditions with little or no skeletal involvement. This transporter is essential for lysosomal function in mice. We demonstrate the expression of Slc29a3 in mouse osteoclasts in vivo. In monocytes from patients with DSS, we observed reduced osteoclast differentiation and function (demineralization of calcium surface). Our report highlights the pleomorphic consequences of dysfunction of this nucleoside transporter, and importantly suggests a new mechanism for the control of osteoclast differentiation and function.

Campeau, Philippe M.; Lu, James T.; Sule, Gautam; Jiang, Ming-Ming; Bae, Yangjin; Madan, Simran; Hogler, Wolfgang; Shaw, Nicholas J.; Mumm, Steven; Gibbs, Richard A.; Whyte, Michael P.; Lee, Brendan H.



[Malignant lymphomas].  


Treatment outcome of malignant lymphomas has been improved since molecular targeted drugs including rituximab became clinically available. However, treatment for relapsed or refractory lymphoma has not been fully established. As second-line therapy for patients with relapsed/refractory follicular lymphoma or diffuse large B cell lymphoma, chemotherapy including alkylating agents or purine analogues, high-dose chemotherapy followed by autologous stem cell transplantation (SCT), and allogeneic SCT are usually selected. Recently, we can also select new therapies including new anti-CD20 monoclonal antibody (MoAb)(IMMU-106(hA20)), anti-CD22 MoAb (epratuzumab), and radioimmunotherapy including Y-90 ibritumomab and I-131 tositumomab. PMID:19461173

Yamaguchi, Yuko; Usui, Noriko



Malignant mesothelioma  

PubMed Central

Malignant Mesothelioma (MM) is a rare but rapidly fatal and aggressive tumor of the pleura and peritoneum with limited knowledge of its natural history. The incidence has increased in the past two decades but still it is a rare tumor. Etiology of all forms of mesothelioma is strongly associated with industrial pollutants, of which asbestos is the principal carcinogen. Mesothelioma is an insidious neoplasm arising from mesothelial surfaces i.e., pleura (65%-70%), peritoneum (30%), tunica vaginalis testis, and pericardium (1%-2%). The diagnosis of peritoneal and Pleural mesothelioma is often delayed, due to a long latent period between onset and symptoms and the common and nonspecific clinical presentation. The definite diagnosis can only be established by diagnostic laparoscopy or open surgery along with biopsy to obtain histological examination and immunocytochemical analysis. Different treatment options are available but Surgery can achieve a complete or incomplete resection and Radical resection is the preferred treatment. Chemotherapy has an important role in palliative treatment. Photodynamic therapy is also an option under trial. Patients who successfully underwent surgical resection had a considerably longer median survival as well as a significantly higher 5-year survival. Source of Data/Study Selection: The data were collected from case reports, cross-sectional studies, Open-label studies and phase –II trials between 1973-2012. Data Extraction: Web sites and other online resources of American college of surgeons, Medline, NCBI and Medscape resource centers were used to extract data. Conclusion: Malignant Mesothelioma (MM) is a rare but rapidly fatal and aggressive tumor with limited knowledge of its natural history. The diagnosis of peritoneal and Pleural mesothelioma is often delayed, so level of index of suspicion must be kept high.

Ahmed, Ishtiaq; Ahmed Tipu, Salman; Ishtiaq, Sundas



Malignant mesothelioma.  


Malignant Mesothelioma (MM) is a rare but rapidly fatal and aggressive tumor of the pleura and peritoneum with limited knowledge of its natural history. The incidence has increased in the past two decades but still it is a rare tumor. Etiology of all forms of mesothelioma is strongly associated with industrial pollutants, of which asbestos is the principal carcinogen. Mesothelioma is an insidious neoplasm arising from mesothelial surfaces i.e., pleura (65%-70%), peritoneum (30%), tunica vaginalis testis, and pericardium (1%-2%). The diagnosis of peritoneal and Pleural mesothelioma is often delayed, due to a long latent period between onset and symptoms and the common and nonspecific clinical presentation. The definite diagnosis can only be established by diagnostic laparoscopy or open surgery along with biopsy to obtain histological examination and immunocytochemical analysis. Different treatment options are available but Surgery can achieve a complete or incomplete resection and Radical resection is the preferred treatment. Chemotherapy has an important role in palliative treatment. Photodynamic therapy is also an option under trial. Patients who successfully underwent surgical resection had a considerably longer median survival as well as a significantly higher 5-year survival. Source of Data/Study Selection: The data were collected from case reports, cross-sectional studies, Open-label studies and phase -II trials between 1973-2012. Data Extraction: Web sites and other online resources of American college of surgeons, Medline, NCBI and Medscape resource centers were used to extract data. Conclusion: Malignant Mesothelioma (MM) is a rare but rapidly fatal and aggressive tumor with limited knowledge of its natural history. The diagnosis of peritoneal and Pleural mesothelioma is often delayed, so level of index of suspicion must be kept high. PMID:24550969

Ahmed, Ishtiaq; Ahmed Tipu, Salman; Ishtiaq, Sundas



Infantile Subdural Hematomas due to Traffic Accidents  

Microsoft Academic Search

The most common cause of subdural hematomas (SDH) in infants is shaken-baby syndrome (SBS). The pathogenesis and natural history of infantile SDH (ISDH) are poorly documented, because in SBS, the date of shaking is usually imprecise and the assault is often repeated. Victims of traffic accidents (TA) form a study group close to experimental conditions, because the trauma is unique,

Matthieu Vinchon; Odile Noizet; Sabine Defoort-Dhellemmes; Gustavo Soto-Ares; Patrick Dhellemmes



Hypsarrhythmia and infantile autism: A clinical report  

Microsoft Academic Search

The case histories of five children, four boys and one girl (1 to 9 years of age), who developed autistic behavior after the onset of infantile spasms, are presented in detail. The patients' initial EEGs disclosed hypsarrhythmia. First onsets of seizures occurred during the second 6 months of life in four and on the third day of life in the

Lawrence T. Taft; Herbert J. Cohen



Early infantile autism and autistic psychopathy  

Microsoft Academic Search

Early infantile autism and autistic psychopathy were first reported within the span of 1 year (1943–1944). While the former (Kanner's syndrome) has become the widely known focus of intensive investigation, the latter (Asperger's syndrome) did not receive the attention it deserves. Often the two conditions mistakenly have been thought to be identical. This paper tries (a) to assign to autistic

D. Arn Van Krevelen



Infantile digital fibromatosis — a case report  

Microsoft Academic Search

Infantile digital fibromatosis (IDF) is a form of fibromatosis usually restricted to childhood. Typically occuring on fingers and toes of children and rarely in the oral cavity [Canioni et al. Pathol. Res. Pract. 187 (1991) 886] and in adults [Viale et al. Histopathology 12 (1998) 415]. It was first described by Reye [Arch. Pathol. Lab. Med. 80 (1965) 228]. IDF

Paul Thomas Chirayil; Jayakish Jayaraj; Pramod Kumar



Infantile Amnesia: Forgotten but Not Gone  

ERIC Educational Resources Information Center

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…

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



Infantile spasms in tuberous sclerosis complex  

Microsoft Academic Search

The high incidence of infantile spasms (IS) and hypsarrhythmia in tuberous sclerosis complex (TSC) has long been emphasized but it is now clear that infants with TSC show clinical and EEG differences from those with classical West syndrome. Seizures at onset are mainly characterized by partial motor seizures and IS. Subtle partial seizures may be present in the early neonatal

Paolo Curatolo; Stefano Seri; Magda Verdecchia; Roberta Bombardieri



Hemispheric asymmetries and early infantile autism  

Microsoft Academic Search

The observation that language disorders constitute a major symptom of early infantile autism has led some researchers to speculate that the autistic syndrome may be a result of brain damage to the left hemisphere. Such speculation has fostered a number of studies in which attempts have been made to link autism with ostensibly positive signs of left hemisphere damage, such

Barbara S. McCann



Infantile myofibromatosis of the craniovertebral junction.  


Infantile myofibromatosis (IM) is a rare pathological entity characterized by solitary or multiple nodular skin, soft tissues or bony lesions. Craniovertebral (CV) junction lesions are rare. We report the successful management of a solitary IM involving the posterior elements of the CV junction in a 6-month-old child. PMID:18661320

Sinha, A K; Jesudason, E C; Mallucci, C L; Losty, P D; Kokai, G; Pizer, B L



ACTH therapy in infantile spasms: side effects  

Microsoft Academic Search

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

R Riikonen; M Donner



Best age for surgery for infantile esotropia  

Microsoft Academic Search

Infantile esotropia (IE) is defined as an esotropia before the age of 6 months, with a large angle, latent nystagmus, dissociated vertical deviation, limitation of abduction, and reduced binocular vision, without neurological disorder. Prematurity, low birth weight, and low Apgar scores are significant risk factors for IE. US standard age of first surgery is 12–18 months, in Europe 2–3 years.

H. J. Simonsz; G. H. Kolling



A Formula for Early Infantile Autism.  

ERIC Educational Resources Information Center

Offered is an explanation for the development of early infantile autism as defined by L. Kanner which incorporates the behavior of the child, the behavior of the parent, and a critical time period of development. Writings of Kanner on the characteristics of autistic children, parental characteristics, and etiology are reviewed. The formula…

Roy, M. Aaron


Malignant hyperpyrexia  

PubMed Central

The history, clinical presentation, and management of malignant hyperpyrexia are presented. The aetiology seems to be associated with some inherited abnormality which affects the movement and binding of calcium ions in the sarcoplasmic reticulum, sarcoplasm, and mitochondria. Whether this is a primary muscular defect or secondary to some trophic neural influence is yet to be established. The subjects carrying the abnormal trait show evidence of a myopathy which is subclinical in most instances and revealed only by estimation of serum CPK or biopsy. In some families where the myopathy is clinically obvious there may be, in addition, a variety of musculoskeletal abnormalities. A plea is made for routine monitoring of temperature during anaesthesia and for procainamide or procaine to be readily available in all operating theatres. A history of anaesthetic deaths in a family calls for special care, and, if the serum CPK is elevated, suxamethonium and halothane are to be avoided. Families with orthopaedic and muscular abnormalities are at increased risk and should have estimation of serum CPK before surgery. As a bonus of this study it is suggested that serum CPK estimations be used to screen pigs for selective breeding and so eliminate the disease, which causes soft exudative pork. Images

Isaacs, Hyam; Barlow, M. B.



A comparison of osteoclast-rich and osteoclast-poor osteopetrosis in adult mice sheds light on the role of the osteoclast in coupling bone resorption and bone formation.  


Osteopetrosis due to lack of acid secretion by osteoclasts is characterized by abolished bone resorption, increased osteoclast numbers, but normal or even increased bone formation. In contrast, osteoclast-poor osteopetrosis appears to have less osteoblasts and reduced bone formation, indicating that osteoclasts are important for regulating osteoblast activity. To illuminate the role of the osteoclast in controlling bone remodeling, we transplanted irradiated skeletally mature 3-month old wild-type mice with hematopoietic stem cells (HSCs) to generate either an osteoclast-rich or osteoclast-poor adult osteopetrosis model. We used fetal liver HSCs from (1) oc/oc mice, (2) RANK KO mice, and (3) compared these to wt control cells. TRAP5b activity, a marker of osteoclast number and size, was increased in the oc/oc recipients, while a significant reduction was seen in the RANK KO recipients. In contrast, the bone resorption marker CTX-I was similarly decreased in both groups. Both oc/oc and Rank KO recipients developed a mild osteopetrotic phenotype. However, the osteoclast-rich oc/oc recipients showed higher trabecular bone volume (40 %), increased bone strength (66 %), and increased bone formation rate (54 %) in trabecular bone, while RANK KO recipients showed only minor trends compared to control recipients. We here show that maintaining non-resorbing osteoclasts, as opposed to reducing the osteoclasts, leads to increased bone formation, bone volume, and ultimately higher bone strength in vivo, which indicates that osteoclasts are sources of anabolic molecules for the osteoblasts. PMID:24838599

Thudium, Christian S; Moscatelli, Ilana; Flores, Carmen; Thomsen, Jesper S; Brüel, Annemarie; Gudmann, Natasja Stæhr; Hauge, Ellen-Margrethe; Karsdal, Morten A; Richter, Johan; Henriksen, Kim



Infantile myofibromatosis presenting with scalp dermoid cyst.  


Infantile myofibromatosis is a disorder of infancy and early childhood, typically presenting as a solitary lesion or multiple widespread nodular tumors localized to skin, subcutaneous tissue, muscle, bone, viscera, or central nervous system. We present a case of infantile myofibromatosis, multicentric type, in a 4-month-old male infant who initially presented with an occipital scalp mass and other skin-colored nodular mass lesions over his face, trunk, and four limbs. He received tissue biopsy to establish a definite diagnosis. Craniotomy was also arranged for tumor removal due to dural involvement with internal extension and compression of adjacent sigmoid sinus. The patient eventually died of cardiopulmonary failure secondary to primary pulmonary hypertension at age 11 months. Before his death, he had suffered from abdominal distention and frequent vomiting, followed by aggravated respiratory distress and cyanosis. Aggressive surveillance for cardiopulmonary or gastrointestinal involvement is recommended in such cases because prognosis varies according to the involvement of vital organs. PMID:16194733

Huang, Ching-Ju; Lin, Kuang-Lin; Jung, Shih-Ming; Wu, Chieh-Tsai; Wang, Huei-Shyong



[Primary hepatic infantile hemangioendothelioma (author's transl)].  


Primary hepatic infantile hemangioendothelioma is a rare tumor, characterized by its appearance in early infancy as well as by the frequent association with various malformations and with similar angiomatous tumors of other tissues and organs. It may be single or multinodular and it is often complicated by severe peritoneal hemorrhage. Tow histologic types of this tumor are known: tipe 1 is sharply circumscribed and is considered similar to so called capillary hypertrophic hemangioma, while type 2, by showing aggressive, infiltrative and anaplastic features, is rather close to angiosarcoma. Clinical and pathological data concerning two cases of type 2 primary hepatic infantile hemangioendothelioma are reported. On the basis of experimental results and epidemiological data on hepatic angiosarcoma of adults, a possible etiopathogenetic relationship with maternal exposure during pregnancy to dangerous environmental factors is postulated. PMID:1224398

Pollice, L; Pagliarulo, G



Surgery for infantile esotropia: is timing everything?  


Infantile esotropia affects binocular alignment and development of binocular vision. Delayed correction may lead to loss of stereopsis. Waiting for the angle of deviation to stabilise prior to surgery does not impact overall postoperative outcomes greatly. Early surgical intervention produces better outcomes in terms of sensory and motor development, binocular vision and stereoacuity. The period of misalignment has the greatest effect on postoperative outcome therefore early surgery is recommended. PMID:23767265

Sarwar, Humera; Waqar, Salman



Infantile refsum disease in four Amish sibs.  


Infantile Refsum disease (IRD) appears with varying degrees of impaired vision, hearing loss, developmental delays, and neuromotor deficiencies. We report on four Amish sibs with IRD from a consanguineous marriage; biochemical testing supported the diagnosis of IRD. Of particular interest in this sibship are characteristic poorly formed yellow-orange teeth in at least three of the four affected sibs and behavior problems in the affected females. PMID:10607947

Bader, P I; Dougherty, S; Cangany, N; Raymond, G; Jackson, C E



Malignant or Accelarated Hypertension  

PubMed Central

Malignant or accelarated hypertension is a life-threatening medical emergency that is a possible complication of practically any hypertensive disorder. If not promptly treated it can cause severe, rapidly progressive target-organ damage and death. While the histo-pathologic features of malignant hypertension are well recognized, the pathogenesis of the associated vascular lesions and the transition from a benign to a malignant phase are unclear. With adequate control of hypertension, progression to the accelarated or malignant phase can be prevented. Moreover, promptly and effectively reducing the blood pressure during the malignant phase can prevent, minimize or even reverse serious target organ injury. Malignant hypertension, therefore, is both preventable and treatable.

Vaziri, N. D.



Extending Childhood into the Teen Years: "Infantilization" and Its Consequences  

ERIC Educational Resources Information Center

Young people sandwiched between childhood and adulthood often rebel when adults treat them like children rather than with the respect that acknowledges their intelligence and potential. Research and theory supporting the view of "infantilizing" adolescents has proliferated. The extent to which modern cultures infantilize youth is evident in…

Skager, Rodney



Part Two: Infantile Spasms--The New Consensus  

ERIC Educational Resources Information Center

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…

Pellock, John M.; O'Hara, Kathryn



Stereopsis and binocular vision after surgery for unilateral infantile cataract  

Microsoft Academic Search

Purpose: To assess the prevalence and level of binocular function in children with unilateral congenital or very early infantile cataract. Methods: We retrospectively reviewed the charts of all patients with unilateral congenital or very early infantile cataract who underwent operation before 4 months of age, at the W. K. Kellogg Eye Center\\/University of Michigan Hospitals, from 1985 to 1995. Amblyopia

Sandra M. Brown; Steven Archer; Monte A. Del Monte



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

Microsoft Academic Search

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

Shahnaz Ibrahim; Shamshad Gulab; Sidra Ishaque; Taimur Saleem



Malignant teratoma (image)  


A malignant teratoma is a type of cancer consisting of cysts that contain one or more of the three ... embryonic germ layers: ectoderm, mesoderm, and endoderm. Because malignant teratomas have usually spread by the time of ...


Looking for new treatments of Infantile Colic  

PubMed Central

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.



Looking for new treatments of Infantile Colic.  


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

Savino, Francesco; Ceratto, Simone; De Marco, Angela; Cordero di Montezemolo, Luca



Natural History of Infantile GM2 Gangliosidosis  

PubMed Central

OBJECTIVE: GM2 gangliosidoses are caused by an inherited deficiency of lysosomal ?-hexosaminidase and result in ganglioside accumulation in the brain. Onset during infancy leads to rapid neurodegeneration and death before 4 years of age. We set out to quantify the rate of functional decline in infantile GM2 gangliosidosis on the basis of patient surveys and a comprehensive review of existing literature. METHODS: Patients with infantile GM2 gangliosidosis (N = 237) were surveyed via questionnaire by the National Tay Sachs & Allied Diseases Association (NTSAD). These data were supplemented by survival data from the NTSAD database and a literature survey. Detailed retrospective surveys from 97 patients were available. Five patients who had received hematopoietic stem cell transplantation were evaluated separately. The mortality rate of the remaining 92 patients was comparable to that of the 103 patients from the NTSAD database and 121 patients reported in the literature. RESULTS: Common symptoms at onset were developmental arrest (83%), startling (65%), and hypotonia (60%). All 55 patients who had learned to sit without support lost that ability within 1 year. Individual functional measures correlated with each other but not with survival. Gastric tube placement was associated with prolonged survival. Tay Sachs and Sandhoff variants did not differ. Hematopoietic stem cell transplantation was not associated with prolonged survival. CONCLUSIONS: We studied the timing of regression in 97 cases of infantile GM2 gangliosidosis and conclude that clinical disease progression does not correlate with survival, likely because of the impact of improved supportive care over time. However, functional measures are quantifiable and can inform power calculations and study design of future interventions.

Bley, Annette E.; Giannikopoulos, Ourania A.; Hayden, Doug; Kubilus, Kim; Tifft, Cynthia J.



Advances in infantile hypertrophic pyloric stenosis.  


Infantile hypertrophic pyloric stenosis (IHPS) is a common condition in infancy, characterized by an acquired narrowing of the pylorus, which requires surgery. These infants usually present with projectile, nonbilious vomiting, with a palpable 'olive' in the abdomen and sometimes a 'peristaltic wave' after being fed with formula or breast milk. Although IHPS is a common disorder, its etiology is largely unknown. Surgical intervention is the standard treatment, preoperative preparation, however is essential to optimal outcome. In this review, the latest advances in IHPS regarding epidemiology, etiology, diagnostics and treatment will be discussed. PMID:24716658

Peters, Babette; Oomen, Mathijs Wn; Bakx, Roel; Benninga, Marc A



Effect of hemispherectomy in infantile hemiplegics.  


Four patients with infantile hemiplegia who had undergone hemispherectomy were examined. both left (LH) and right (RH) hemidecorticates obtained borderline defective scores on IQ tests. Patients with isolated right hemispheres were found not to be aphasic or apraxic. Visuospatial and constructional capacities were compromised in all patients. Individuals with an isolated right hemisphere smiled and gestured more than did those with an isolated right hemisphere. EEG and CT scan data showed that the remaining hemisphere was not normal in these patients. Therefore, inferences regarding the functional plasticity of the remaining hemisphere must be made with caution. PMID:6626937

Strauss, E; Verity, C



Conjugated hyperbilibubinaemia in infancy (infantile cholestasis).  


The finding of high conjugated bilirubin needs prompt evaluation to rule out liver or bile duct pathology. If assessment of total and direct bilirubin is carried routinely in any infant whose jaundice persists for more than 2 weeks, early identification of a group of children who need corrective surgery for atresia of the extra hepatic bile duct is possible. The aim of this review is to look at common causes of infantile cholestasis with emphasis on evaluation, diagnosis, complications, treatment and outcome of infant with neonatal cholestasis. PMID:19864861

Abdullah, A M



Factors associated with infantile hypertrophic pyloric stenosis.  


We examined perinatal factors in relation to the rise in incidence of infantile hypertrophic pyloric stenosis among children in Olmsted County, Minnesota, during the period from 1950 through 1984. Primogeniture was associated with male infants but not female infants; some factor related to primogeniture, such as breast-feeding, may be etiologically important. Our data did not support a role for maternal disease, use of doxylamine succinate-pyridoxide hydrochloride (Bendectin), or an infectious process. Further study should be directed toward environmental factors associated with primogeniture. PMID:3344722

Jedd, M B; Melton, L J; Griffin, M R; Kaufman, B; Hoffman, A D; Broughton, D; O'Brien, P C



Propranolol treatment of infantile hemangioma endothelial cells: A molecular analysis  

PubMed Central

Infantile hemangiomas (IHs) are non-malignant, largely cutaneous vascular tumors affecting approximately 5–10% of children to varying degrees. During the first year of life, these tumors are strongly proliferative, reaching an average size ranging from 2 to 20 cm. These lesions subsequently stabilize, undergo a spontaneous slow involution and are fully regressed by 5 to 10 years of age. Systemic treatment of infants with the non-selective ?-adrenergic receptor blocker, propranolol, has demonstrated remarkable efficacy in reducing the size and appearance of IHs. However, the mechanism by which this occurs is largely unknown. In this study, we sought to understand the molecular mechanisms underlying the effectiveness of ? blocker treatment in IHs. Our data reveal that propranolol treatment of IH endothelial cells, as well as a panel of normal primary endothelial cells, blocks endothelial cell proliferation, migration, and formation of the actin cytoskeleton coincident with alterations in vascular endothelial growth factor receptor-2 (VEGFR-2), p38 and cofilin signaling. Moreover, propranolol induces major alterations in the protein levels of key cyclins and cyclin-dependent kinase inhibitors, and modulates global gene expression patterns with a particular affect on genes involved in lipid/sterol metabolism, cell cycle regulation, angiogenesis and ubiquitination. Interestingly, the effects of propranolol were endothelial cell-type independent, affecting the properties of IH endothelial cells at similar levels to that observed in neonatal dermal microvascular and coronary artery endothelial cells. This data suggests that while propranolol markedly inhibits hemangioma and normal endothelial cell function, its lack of endothelial cell specificity hints that the efficacy of this drug in the treatment of IHs may be more complex than simply blockage of endothelial function as previously believed.




COSMC Is Overexpressed in Proliferating Infantile Hemangioma and Enhances Endothelial Cell Growth via VEGFR2  

PubMed Central

Infantile hemangiomas are localized lesions comprised primarily of aberrant endothelial cells. COSMC plays a crucial role in blood vessel formation and is characterized as a molecular chaperone of T-synthase which catalyzes the synthesis of T antigen (Gal?1,3GalNAc). T antigen expression is associated with tumor malignancy in many cancers. However, roles of COSMC in infantile hemangioma are still unclear. In this study, immunohistochemistry showed that COSMC was upregulated in proliferating hemangiomas compared with involuted hemangiomas. Higher levels of T antigen expression were also observed in the proliferating hemangioma. Overexpression of COSMC significantly enhanced cell growth and phosphorylation of AKT and ERK in human umbilical vein endothelial cells (HUVECs). Conversely, knockdown of COSMC with siRNA inhibited endothelial cell growth. Mechanistic investigation showed that O-glycans were present on VEGFR2 and these structures were modulated by COSMC. Furthermore, VEGFR2 degradation was delayed by COSMC overexpression and facilitated by COSMC knockdown. We also showed that COSMC was able to regulate VEGF-triggered phosphorylation of VEGFR2. Our results suggest that COSMC is a novel regulator for VEGFR2 signaling in endothelial cells and dysregulation of COSMC expression may contribute to the pathogenesis of hemangioma.

Lee, Jian-Jr; Huang, Miao-Juei; Huang, John; Hung, Ji-Shiang; Chen, Ming-Ting; Huang, Min-Chuan



Precursors to Lymphoproliferative Malignancies  

PubMed Central

We review monoclonal B-cell lymphocytosis (MBL) as a precursor to chronic lymphocytic leukemia and monoclonal gammopathy of undetermined significance (MGUS) as a precursor to plasma cell disorders. These conditions are present in the general population and increase with age. These precursors aggregate with lymphoproliferative malignancies in families suggesting shared inheritance. MBL and MGUS may share some of the same risk factors as their related malignancies but data are limited. While these conditions are characterized by enhanced risk for the associated malignancy, the majority of individuals with these conditions do not progress to malignancy. A key focus for current work is to identify markers that predict progression to malignancy.

Goldin, Lynn R.; McMaster, Mary L.; Caporaso, Neil E.



Update on infantile colic and management options.  


Infant colic is a common but poorly defined and understood clinical entity and, while several causative factors have been suggested, a unifying theory of its pathogenesis is still required. Food hypersensitivity/allergy and gut dysmotility are the lead contenders for causative factors of infantile colic. Additional confounders and covariables include psychological and social factors. Although the available data fail to provide insight into the exact triggers of infantile colic, these do allow for the hypothesis that certain infants are predisposed to dietary protein intolerance and disturbed gut motility, such as visceral hypersensitivity/ hyperalgesia, in the first few weeks of life. These processes lead to distress and altered perceptions, where normal stimuli (ie, intestinal distension) are misinterpreted as painful events. This review discusses a number of interventions, including pharmacological agents, which are based on the perceived pathogenesis; however, it is likely that infants with colic will require a multifactorial management strategy. Healthcare providers must offer support, reassurance and empathy to the caregiver, and adopt a biopsychosocial approach to the infants and their families by considering any underlying medical diseases in addition to examining the family unit. In a small subset of infants with colicky behavior, a specific medical disorder such as gastroesophageal reflux or milk protein allergy may be identified. While the vast majority of infants with colic will recover uneventfully, some may be at risk for the later development of behavioral problems and atopy/allergy. PMID:17979025

Gupta, Sandeep K



Congenital infantile fibrosarcoma: Association with bleeding diathesis  

PubMed Central

Patient: Male, 2 month Final Diagnosis: Congenital infantile fibrosarcoma Symptoms: Bleeding Medication: Vincristine • actinomycin • cyclophosphamide Clinical Procedure: Surgical resection Specialty: Pediatric Oncology Objective: Diagnostic/therapeutic accidents Background: Congenital infantile fibrosarcoma (CIF) is a soft-tissue tumor occurring during the first 2 years of life, most commonly in the extremities. CIF is frequently initially misdiagnosed as a vascular tumor, but its association with bleeding and coagulopathy has not been well characterized. Case Reports: We describe 2 infants with CIF presenting with bleeding and coagulopathy, requiring urgent intervention. Both patients did well; one underwent partial resection followed by chemotherapy, and the other received 2 cycles of chemotherapy followed by gross total resection. We also provide a review of all reported cases of coagulopathy in the setting of CIF in the English literature, uncovering an association that seems to be more prevalent in patients diagnosed in the neonatal period, with associated anemia and thrombocytopenia, and a significant mortality rate. Conclusions: CIF needs to be considered in the differential diagnosis of vascular congenital tumors, especially when there is evidence of bleeding, anemia, or thrombocytopenia.

Salman, Mayssaa; Khoury, Nabil J.; Khalifeh, Ibrahim; Abbas, Hussein A.; Majdalani, Marianne; Abboud, Miguel; Muwakkit, Samar; Solh, Hassan El; Saab, Raya



Two new familial severe infantile spasm syndromes in males.  


We describe two new familial severe infantile spasm syndromes (ISSs) unrelated to Aristaless-related homeobox (ARX) gene mutation. Family A contains two male siblings each with dysmorphism, profound psychomotor delay, gastroesophageal reflux, infantile spasms, hypsarrhythmia, prominent independent central apneas, and early death. Family B contains two male siblings with dysmorphism, profound psychomotor delay, ambiguous genitalia, macular hypoplasia, neurosensory hearing deficit, gastroesophageal reflux, infantile spasms, no hypsarrhythmia, apneas, and early death in one sibling. Etiologic workup and ARX gene sequencing were negative. This indicates that several familial ISSs exist but are not genetically characterized. PMID:19232548

Karam, Pascale E; Farra, Chantal; Shamseddine, Alhan; Mikati, Mohamad A



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

PubMed Central

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.

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



Genetics Home Reference: Late-infantile neuronal ceroid lipofuscinosis  


... movements (ataxia). Affected children also develop muscle twitches (myoclonus) and vision impairment. Late-infantile NCL affects motor ... endoplasmic reticulum ; enzyme ; epilepsy ; gene ; inherited ; lysosome ; motor ; myoclonus ; nervous system ; prevalence ; protein ; recessive ; regression You may ...


Studies on the Etiology of Autumnal Infantile Acute Gastroenteritis - Rotavirus.  

National Technical Information Service (NTIS)

The etiology of autumnal infantile acute gastroenteritis which occurred in 1978 in Beijing was studied. Typical rotavirus particles were found by electron microscopy in stool samples of 11 out of 32 cases. Rotavirus complement-fixing antigen was demonstra...

Q. Pang F. Qui F. Yu S. Chen Y. Suo



Rheumatic Diseases and Malignancies  

PubMed Central

ABSTRACT There are many studies which demonstrate a higher risk for malignancy in patients with rheumatic diseases. There have been a number of possible explanations for the differences in the risk of certain malignancies in patients with rheumatic disease, compared with general population, but a clear mechanism is difficult to identify. Rheumatoid syndromes may be associated with malignancy as paraneoplastic conditions, which can antedate the neoplasm diagnosis. On the other hand, autoimmune rheumatic diseases have a higher risk of malignancy by themselves or because of the immunosuppressant treatments.

BOJINCA, Violeta; JANTA, Iustina



Spatial-Bisection Acuity in Infantile Nystagmus  

PubMed Central

This study measured spatial bisection acuity for horizontally and vertically separated line targets in 5 observers with infantile nystagmus syndrome (INS) and no obvious associated sensory abnormalities, and in two normal observers during comparable horizontal retinal image motion. For small spatial separations between the line targets, bisection acuity for both horizontally and vertically separated lines is worse in the observers with IN than normal observers. In four of the five observers with IN, bisection acuity for small target separations is poorer for horizontally compared to vertically separated lines. Because the motion smear generated by the retinal image motion during IN would be expected influence horizontally separated targets, the degradation of bisection acuity for both vertical and horizontally separated lines indicates that a sensory neural deficit contributes to impaired visual functioning in observers with idiopathic IN.

Ukwade, Michael T.; Bedell, Harold E.



Infantile parkinsonism-dystonia: a dopamine "transportopathy"  

PubMed Central

The dopamine transporter (DAT) retrieves the neurotransmitter dopamine from the synaptic cleft at dopaminergic synapses. Variations in solute carrier family 6A, member 3 (SLC6A3/DAT1), the human gene encoding DAT, have been implicated in attention deficit hyperactivity and bipolar disorders, and DAT is a prominent site of action for drugs such as amphetamines and cocaine. In this issue of the JCI, Kurian et al. report that an autosomal recessive infantile parkinsonism-dystonia is caused by loss-of-function mutations in DAT that impair dopamine reuptake (see the related article beginning on page 1595). Though this might be predicted to result in dopamine excess in the synaptic cleft, it likely also causes depletion of presynaptic dopamine stores and possibly downregulation of postsynaptic dopamine receptor function, resulting in impairments in dopaminergic neurotransmission consistent with the clinical presentation. This is the first report of a genetic alteration in DAT function underlying a parkinsonian disorder.

Blackstone, Craig



Surgical management of large scalp infantile hemangiomas  

PubMed Central

Background: Infantile Hemangiomas (IH) are the most common benign tumor of infancy, occurring in over 10% of newborns. While most IHs involute and never require intervention, some scalp IHs may cause severe cosmetic deformity and threaten tissue integrity that requires surgical excision. Case Description: We present our experience with two infants who presented with large scalp IH. After vascular imaging, the patients underwent surgical resection of the IH and primary wound closure with excellent cosmetic outcome. We detail the surgical management of these cases and review the relevant literature. Conclusion: In some cases the IHs leave behind fibro-fatty residuum causing contour deformity. Surgery is often required for very large lesions causing extensive anatomical and/or functional disruption. The goal of surgical intervention is to restore normal anatomic contour and shape while minimizing the size of the permanent scar.

Khan, Imad S.; Kiehna, Erin N.; Satti, Komal F.; Ehtesham, Moneeb; Ghiassi, Mahan; Singer, Robert J.



A genetic and biologic classification of infantile spasms  

PubMed Central

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.

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



AIDS-Related Malignancies  

Microsoft Academic Search

OVERVIEW OF MALIGNANCY IN PATIENTS WITH AIDS Despite the advent of highly active antiretroviral therapy, the incidence of human immunodeficiency virus (HIV)-asso- ciated malignancies has not decreased. The United States Centers for Disease Control (CDC) has determined that Kaposi's sarcoma, non-Hodgkin's lymphoma (including pri- mary central nervous system lymphoma), and cervical carci- noma define the acquired immune deficiency syndrome (AIDS).



Treatment of infantile hepatoblastoma and related complications  

Microsoft Academic Search

Hepatorblastoma is an uncommon childhood malignant tumor of hepatic origin and recent progress of treatment strategy resulted in improved prognosis of patients with hepatoblastoma. Although patients within one year of age were considered to have bet- ter prognosis than those over that age, the treatment related deaths have been reported to be the only cause of the treatment failure of

Shigeru UENO; Hitoshi HIRAKAWA; Seishichi YOKOYAMA; Tomoya HINOKI; Kosuke TOBITA; Yasuo OHTANI; Toshihide IMAIZUMI; Hiroyasu MAKUUCHI; Yoshio IWATA; Yutaka IMAI



Best age for surgery for infantile esotropia.  


Infantile esotropia (IE) is defined as an esotropia before the age of 6 months, with a large angle, latent nystagmus, dissociated vertical deviation, limitation of abduction, and reduced binocular vision, without neurological disorder. Prematurity, low birth weight, and low Apgar scores are significant risk factors for IE. US standard age of first surgery is 12-18 months, in Europe 2-3 years. The only study to date with prospectively assigned early- and late-surgery groups and evaluation according to intention-to-treat, was the European Early vs. Late Infantile Strabismus Surgery Study (ELISSS). In that study 13.5% of children operated around 20 months vs. 3.9% (P = 0.001) of those operated around 49 months had gross stereopsis (Titmus Housefly) at age 6. The reoperation rate was 28.7% in children operated early vs. 24.6% in those operated late. Unexpectedly, 8% in the early group vs. 20% in the late group had not been operated at age 6, although all had been eligible for surgery at baseline at 11 SD 3.7 months. In most of these children the angle of strabismus decreased spontaneously. In a meta-regression analysis of the ELISSS and 12 other studies we found that reoperation rates were 60-80% for children first operated around age 1 and 25% for children operated around age 4. Based on these findings, the endpoints to consider when contemplating best age for surgery in an individual child with IE should be: (1) degree of binocular vision restored or retained, (2) postoperative angle and long-term stability of the angle and (3) number of operations needed or chance of spontaneous regression. IE is characterized by lack of binocular connections in the visual cortex that cannot develop, e.g. because the eyes squint, or do not develop, e.g. after perinatal hypoxia. As the cause of IE, whether motor or sensory, is a determinant of surgical outcome, a subdivision of IE according to cause is needed. As similarities exist between IE and cerebral palsy we propose to adapt the working definition formulated by the Surveillance of Cerebral Palsy in Europe and define IE as "a group of permanent, but not unchanging, disorders with strabismus and disability of fusional vergence and binocular vision, due to a nonprogressive interference, lesion, or maldevelopment of the immature brain, the orbit, the eyes, or its muscles, that can be differentiated according to location, extent, and timing of the period of development." PMID:21511504

Simonsz, H J; Kolling, G H



Recent advances in the pharmacotherapy of infantile spasms.  


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

Riikonen, Raili



Role of connexins in infantile hemangiomas  

PubMed Central

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.

Blanke, Katja; Dahnert, Ingo; Salameh, Aida



Surgical indications for infantile subdural effusion.  


Thirty-four cases of infantile subdural effusion (ISE) were reviewed in relation to surgical treatment and its prognosis during an average of 4 years of extended follow-up. The surgical indications were determined mainly by the size of the ISE on computed tomography (CT) scan and by metrizamide CT cisternography (MCTC). Consequently, 18 cases were categorized as type A according to MCTC, including 11 cases (61.1%) of ISE CT grade 1. All type A cases were closely observed. This nontreatment regimen yielded excellent results in 15 cases (83.3%). For 10 cases categorized as type B according to MCTC, including 5 cases (50%) of ISE CT grade 3, surgical treatment was indicated and excellent results were obtained in 8 cases (80%). For 6 cases categorized as type C according to MCTC and as ISE CT grade 3, surgery yielded excellent results in 4 cases (66.7%). Antiepileptic drugs have been given to three (27.3%) of the 11 patients who had convulsive attacks. In conclusion, the surgical indications for ISE were based mainly on MCTC in addition to the clinical course, and it is emphasized that, in the early stages, surgery on ISE cases categorized as MCTC types B and C is necessary. PMID:2095304

Sakai, N; Nokura, H; Deguchi, K; Decarlini, E; Futamura, A; Yamada, H



Chemoembolization of hepatic malignancy  

Microsoft Academic Search

Treatment of primary and secondary hepatic malignancies with transarterial chemoembolization (TACE) represents an essential\\u000a component of interventional oncology. This article discusses patient selection, procedure technique, results, and complications\\u000a associated with TACE.

Carin F. Gonsalves; Daniel B. Brown


Chemoembolization of hepatic malignancy  

Microsoft Academic Search

Treatment of primary and secondary hepatic malignancies with transarterial chemoembolization represents an essential component\\u000a of interventional oncology. This article discusses patient selection, procedure technique, results, and complications associated\\u000a with transarterial chemoembolization.

Carin F. Gonsalves; Daniel B. Brown



Gynecologic malignancy in pregnancy  

PubMed Central

Gynecologic malignancy during pregnancy is a stressful problem. For the diagnosis and treatment of malignancy during pregnancy, a multidisciplinary approach is needed. Patients should be advised about the benefits and risk of treatment. When selecting a treatment for malignancy during pregnancy, the physiologic changes that occur with the pregnancy should be considered. Various diagnostic procedures that do not harm the fetus can be used. Laparoscopic surgery or laparotomy may be safely performed. The staging approach and treatment should be standard. Systemic chemotherapy during the first trimester should be delayed if possible. Radiation therapy should preferably start postpartum. Although delivery should be delayed preferably until after 35 weeks of gestation, termination of pregnancy may be considered when immediate treatment is required. Subsequent pregnancies do not increase the risk of malignancy recurrence.

Ji, Yong Il



Thoracic Malignancy Steering Committee

The TMSC functions to harmonize an efficient, cost-effective, science-driven, and transparent process that will identify and promote the "Best Science" in clinical research of lung and other thoracic malignancies by addressing the design and prioritization of phase III trials and large phase II studies in chest malignancies. In addition to focusing on lung cancer, the TMSC addresses oncology trials in other thoracic sites, such as mesothelioma. Esophageal cancer trials are reviewed by the Gastrointestinal Cancer Steering Committee.


Malignant liver tumors.  


The primary hepatic malignancies are a diverse group of neoplasms with distinctive clinical and pathologic features. Imaging of the primary hepatic malignancies continues to be challenging. Ultrasonography, CT scanning, and MR imaging play complementary roles in the evaluation of these patients. Many [figure: see text] of these neoplasms have distinctive imaging features that may permit diagnosis. In most instances, however, biopsy is required for definitive diagnosis and treatment planning. PMID:11933586

Levy, Angela D



Hypertriglyceridaemia and malignancy.  


Severe hypertriglyceridaemia is a rare presentation usually associated with acute pancreatitis. We present two case reports of severe hypertriglyceridaemia occurring in patients with previous autoimmune disease and haematological and solid malignancies but no evidence of prior or concurrent pancreatitis or hyperlipidaemia. These case reports illustrate that haematological and solid organ malignancies and autoimmunity may be relevant as exacerbating factors in the presentation of severe type IV or V hypertriglyceridaemia. PMID:15854204

Wijeratne, S; Wray, R; Collinson, P O; Wierzbicki, A S



Malignant migrating partial seizures in infancy.  


The syndrome of malignant migrating partial seizures in infancy (MMPSI) was first reported in 1995, and is now included among the childhood epileptic syndromes in the revision proposal of the ILAE Commission on classification and terminology. The main clinical features are seizure onset in the first 6 months of life, occurrence of almost continuous migrating polymorphous focal seizures, associated with multifocal ictal EEG discharges, progressive deterioration of psychomotor development combined with frequent evolution of acquired microcephaly, and lack of a significant familial and etiological context. Eventually, children develop major axial hypotonia, pyramidal and extrapyramidal signs with athetotic movements and strabismus. Neuroradiological, biochemical, and genetic investigations thus far have note contributed to our knowledge about this syndrome. Etiology is still unknown, though it appears reasonable to suspect a genetic etiology for MMPSI; a channelopathy may be responsible for the age-dependent cortical neuronal hyperexcitability. Seizures are markedly drug resistant and outcome is generally severe. However, some patients may respond favourably to bromide, stiripentol associated with clonazepam, and, more recently, to levetiracetam. Vagus nerve stimulation and a ketogenic diet have been tried also but with poor or inconclusive results. Based on age at onset, MMPEI may be placed between early epileptic encephalopthies and infantile spasms. PMID:23622207

Coppola, Giangennaro



[Malignant nail tumors].  


Because of the large number of different tissues making up the distal phalanx of fingers and toes, a large variety of malignant tumors can be found in and around the nail apparatus. Bowen disease is probably the most frequent nail malignancy. It is usually seen as a verrucous plaque of the nail fold and nail bed in persons above the age of 40 years. It slowly grows over a period of years or even decades before degenerating to an invasive squamous cell carcinoma. The latter may also occur primarily often as a weeping onycholysis. The next most frequent nail malignancy is ungual melanoma. Those arising from the matrix are usually pigmented and often start with a longitudinal melanonychia whereas those originating from the nail bed remain amelanotic, are often nodular and mistaken for an ingrown nail in an elderly person. The treatment of choice for in situ and early invasive subungual melanomas is generous extirpation of the nail apparatus whereas distal amputation is only indicated for advanced melanomas. In addition to these frequent nail malignancies, nail-specific carcinomas, malignant vascular and osseous tumors, other sarcomas, nail involvement in malignant systemic disorders and metastases may occur. In most cases, they cannot be diagnosed accurately on clinical grounds. Therefore, a high degree of suspicion is necessary in all isolated or single-digit proliferations that do not respond to conservative treatment. PMID:24718507

Haneke, E



Dietary management of infantile colic: a systematic review.  


Infantile colic, the cause of 10-20% of all early paediatrician visits, can lead to parental exhaustion and stress. A systematic review was conducted to examine whether dietary change provides an effective therapy for infantile colic. Six databases were searched from 1960, and 24 studies selected for inclusion. In breastfed infants, evidence suggests that a hypoallergenic maternal diet may be beneficial for reducing symptoms of colic. In formula-fed infants, colic may improve after changing from a standard cow's milk formula to either a hydrolysed protein formula or a soy-based formula. Fibre-supplemented formulae had no effect. Removal of poorly digested carbohydrates from the infant's diet has promise, but additional clinical studies must be conducted before a recommendation can be made. Use of a universal definition to measure symptoms of infantile colic and consistent analysis of urine and faecal samples would improve the evidence in this area. PMID:21710185

Iacovou, Marina; Ralston, Robin A; Muir, Jane; Walker, Karen Z; Truby, Helen



Infantile Spasms: A Critical Review of Emerging Animal Models  

PubMed Central

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.

Stafstrom, Carl E



Obesity and increasing rate of infantile blount disease.  


Background. The incidence of infantile Blount disease is rising in parallel to the increasing obesity in children. Material and methods. Seven children (3 female) between the ages of 17 and 30 months (21.8 ± 4.3 months) were included in the study. Results. All patients had complaints of inward bowing of the legs and excess weight gain. The biochemical and hormonal assessments of all patients yielded normal results. Patients were diagnosed with infantile Blount disease based on clinical, laboratory, and radiological findings. Conclusion. This disease should be differentiated from physiological genu varum, and the potential psychosocial and physical complications are prevented with early diagnosis and treatment. PMID:24419262

Güven, Ayla; Hanc?l?, Suna; Kuru, L Ihsan



Hemostasis and malignancy.  


There is considerable evidence that the hemostatic system is involved in the growth and spread of malignant disease. There is an increased incidence of thromboembolic disease in patients with cancers and hemostatic abnormalities are extremely common in such patients. Antihemostatic agents have been successfully used to treat a variety of experimental tumors, and several clinical trials in humans have been initiated. Although metastasis is undoubtedly multifactorial, intravascular coagulation activation and peritumor fibrin deposition seem to be important. The mechanisms by which hemostatic activation facilitates the malignant process remain to be completely elucidated. Of central importance may be the presence on malignant cells of tissue factor and urokinase receptor. Recent studies have suggested that these proteins, and others, may be involved at several stages of metastasis, including the key event of neovascularization. Tissue factor, the principal initiator of coagulation, may have additional roles, outside of fibrin formation, that are central to the biology of some solid tumors. PMID:9579631

Francis, J L; Biggerstaff, J; Amirkhosravi, A



Malignant pleural disease.  


The vast majority of pleural neoplasms invade the pleura secondarily and can be seen in patients with bronchogenic carcinoma, breast cancer, lymphoma, and ovarian or gastric carcinoma. Primary pleural neoplasms are less common, although they have developed notoriety since the up-surge of malignant mesothelioma and the knowledge of its connection to asbestos exposure. Other malignant primary tumors include localized fibrous tumor and pleural liposarcoma. In most patients with diffuse malignant pleural disease the chest radiograph shows pleural effusion with or without pleural thickening. Computed tomography (CT) usually provides precise localization and extent of the disease and may be of value in assessing chest wall and mediastinal involvement. In specific situations, magnetic resonance (MR) may be useful as a problem-solving tool when CT findings of chest wall or diaphragmatic invasion are equivocal or in patients with contraindication to intravenous administration of ionic contrast material. PMID:10874176

Bonomo, L; Feragalli, B; Sacco, R; Merlino, B; Storto, M L



Malignant Vestibular Schwannoma  

PubMed Central

A 61-year-old woman underwent a translabyrinthine resection of a right intracanulicular acoustic neuroma, which had been detected in the work-up of sudden hearing loss. At the time of surgery, the tumor was roughly twice as large as indicated by the magnetic resonance scan taken only 2 months previously. The tumor eroded the vertical and transverse crests and extended well into the cerebellopontine angle. It was impossible to distinguish the facial nerve proximal to the geniculate ganglion. All visible tumor was resected, along with the facial nerve. Histological evaluation showed a highly cellular tumor, with many mitoses and areas of necrosis, meeting the criteria for malignant schwannoma. The patient has no stigmata of neurofibromatosis, and has no known relatives with that condition. This case is only the fourth reported of a malignant vestibular schwannoma. The relationships between vestibular schwannoma, neurofibromatosis, and malignancy are discussed. ImagesFigure 2Figure 3Figure 4Figure 5Figure 6

Gruber, B.; Petchenik, L.; Williams, M.; Thomas, C.; Luken, M.G.



Extracutaneous malignant melanomas.  


Extracutaneous malignant melanomas are rare tumors with vexing clinical presentation and grim prognosis. Only 4%-5% of all primary melanomas do not arise from the skin. These tumors are almost uniformly fatal, even in 2006. Although a fairly good number of these lesions were reported in the literature, the lack of a side-by-side analysis of these studies has resulted in tentative conclusions that merely offer a first glimpse at the clinicopathologic diversity of these lesions. To remedy this issue, this article took an aim at presenting a literature review concerning extracutaneous malignant melanomas. It also reports several cases of extracutaneous melanomas, which I came across in my 15 years of surgical and molecular pathology practice. The study raises several notions. Extracutaneous malignant melanomas are rare but extremely aggressive lesions with a grim outcome. They include ocular, metastatic, anorectal, mucosal, nail beds, conjunctival, vaginal, urogenital, orbital, esophageal, and leptomeningial malignant melanomas. The development of these lesions lacks an association with sun damage, family history, or precursor nevi. These lesions cause considerable diagnostic consternation and their distinction from other types of tumors (such as undifferentiated carcinomas, high-grade sarcomas, and lymphomas) is critical both from a diagnostic and prognostic point of view. In the proper clinical, histological, and cytological context, immunopositivity for S100 protein, HMB45, and vimentin allows the distinction of these malignant melanomas from other histologically similar malignancies. To conclude, extracutaneous melanoma should be considered while undifferentiated neoplasms, especially those displaying prominent eosinophilic nucleoli, and the coexistence of epithelioid and spindle cells. Special staining and immunohistochemistry should be resorted to establish the diagnosis. PMID:18568775

Hussein, Mahmoud R



Immunotherapy of Genitourinary Malignancies  

PubMed Central

Most cancer patients are treated with some combination of surgery, radiation, and chemotherapy. Despite recent advances in local therapy with curative intent, chemotherapeutic treatments for metastatic disease often remain unsatisfying due to severe side effects and incomplete long-term remission. Therefore, the evaluation of novel therapeutic options is of great interest. Conventional, along with newer treatment strategies target the immune system that suppresses genitourinary (GU) malignancies. Metastatic renal cell carcinoma and non-muscle-invasive bladder caner represent the most immune-responsive types of all human cancer. This review examines the rationale and emerging evidence supporting the anticancer activity of immunotherapy, against GU malignancies.

Inamoto, Teruo; Azuma, Haruhito



Malignant myoepithelioma of palate.  


Malignant myoepithelioma is a rare salivary gland neoplasm, which accounts for less than 2% of all the salivary gland carcinomas. Majority of cases have been reported in parotid, and only 8 cases of involvement of the hard palate have been reported in the literature so far. Hereby, a case of painless, ulcerated palatal mass of 2 years of duration reported. A diagnosis of malignant plasmacytoid myoepithelioma was made with the aid of immunohistochemical analysis, and wide surgical excision was considered keeping in mind the biological behavior of the tumor. PMID:23293504

Richa; Ray, Jay Gopal; Mohanty, Sweta Pattanayak; Vibha



Malignant peritoneal mesothelioma  

Microsoft Academic Search

Opinion statement  This paper summarizes the author’s thoughts about the use of cytoreductive surgery combined with intraperitoneal hyperthermic\\u000a chemotherapy (CS-IPHC) for treatment of peritoneal malignant mesothelioma. Pleural malignant mesotheliomas are by far more\\u000a common (about ten-to thirty-fold) than the peritoneal variants (2.2 cases per 1 million in the US) [1]. Other locations (pericardium,\\u000a tunica vaginalis) are very rare. It is well

Brian W. Loggie



Diffuse malignant peritoneal mesothelioma.  


Mesothelioma often originates in the pleura and less frequently in the peritoneum. This article describes a rare case of diffuse malignant peritoneal mesothelioma in a 54-year-old male construction worker who was admitted to our hospital with a 2-month history of progressive abdominal distention. Abdominal computed tomography revealed extensive peritoneal nodularity and omental cake along with massive ascites. Imaging findings initially suggested peritoneal carcinomatosis, primary peritoneal carcinoma, and tuberculous peritonitis. Laparoscopic biopsy of the omentum and peritoneum confirmed the diagnosis of malignant peritoneal mesothelioma of epitheloid type. Although systemic chemotherapy was administered, no tumor regression was found. The patient finally died of nosocomial infection. PMID:24183360

Shih, Chih-An; Ho, Szu-Pei; Tsay, Feng-Woei; Lai, Kwok-Hung; Hsu, Ping-I



Malignancy Risk in Vasculitis  

PubMed Central

The vasculitides encompass a rare subset of autoimmune diseases. Reports of the concurrent association of malignancies with some forms of vasculitis raise the possibility that patients with certain types of vasculitis may be at increased risk of cancer. Conversely, some forms of vasculitis may be a manifestation of malignancy. We review cancer risk in patients with large vessel vasculitis (giant cell arteritis and Takayasu arteritis), polyarteritis nodosa, and the circulating antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitides. In addition we discuss vasculitis as a paraneoplastic phenomenon, highlighting polyarteritis nodosa in association with hairy cell leukemia and reviewing the most common vasculitic manifestation of cancer, cutaneous vasculitis.

Kermani, Tanaz A.; Warrington, Kenneth J.; Amin, Shreyasee



Microsurgery for malignant gliomas.  


Reflections directly involving the ongoing, intense research activities in biology, the neurosciences and in neurosurgery are discussed including the evolving diagnostic and treatment modalities of primary and secondary malignant gliomas of the central nervous system. The etiology of this enigmatic disease remains obscure, and a curative therapy is still not available. Nevertheless, as a result of changing paradigms in neuroanatomy, neuropathology, neurophysiology, neuroradiology and in neurosurgery, and taking into account the broader selection of adjuvant therapies available, well circumscribed malignant gliomas, which are in predilected compartments of the brain, can be efficiently resected. Good life quality and a respectable survival time are achieved in the majority of patients. PMID:15527081

Ya?argil, M Gazi; Kadri, Paulo A S; Yasargil, Dianne C H



Computerized tomography of brain in infantile spasms (West syndrome)  

Microsoft Academic Search

Computerized tomographic scanning of the brain was performed in 26 infants with Infantile spasms. Majority of the patients, 18 (69%) had some abnormality. Changes noted were cerebral atrophy in 12, calcifications in 5 and dysgenesis of the corpus callosum in 3 patients. One infant each had porencephaly, hydrocephalus and cavum septum pellucidum. Five patients had more than one abnormality simultaneously.

A. H. Mahdi; M. D. Yohannan; P. J. Patel; T. M. Malabarey; T. M. Kolawole



Alexander disease with mild dorsal brainstem atrophy and infantile spasms.  


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

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



Infantile hydrocephalus and the slit ventricle syndrome in early infancy  

Microsoft Academic Search

Slit ventricle syndrome is well known as a complication in the treatment of hydrocephalus by shunting. It is generally considered to be a chronic (but not acute) complication, occurring years after the shunt procedure; there has been no report of this syndrome occurring before 1 year of age. The authors present infantile cases that developed a severe form of this

Shizuo Oi; Satoshi Matsumoto



The Molecular Basis of Dutch Infantile Nephropathic Cystinosis  

Microsoft Academic Search

Infantile nephropathic cystinosis, an inborn error of metabolism with an autosomal recessive inheritance pattern, is characterized by lysosomal storage of the amino acid cystine due to an impaired transport of cystine out of the lysosomes. Initial clinical features consist of the renal Fanconi syndrome and crystals in the cornea. Oral therapy with cysteamine lowers the intracellular cystine content. Recently, the

Sandra G. Heil; Elena Levtchenko; Leo A. H. Monnens; Frans J. M. Trijbels; Henk J. Blom



Colour Doppler imaging of intracranial vasculopathy in severe infantile sialidosis  

Microsoft Academic Search

Neonatal ascites is usually attributed to prenatal infections, lysosomal storage disease and anomalies of the genitourinary tract, gastrointestinal tract or cardiovascular system. We report one case of neonatal ascites associated with infantile sialidosis. Cerebral sonography showed stripe-like intracerebral echogenicities in the region of the basal ganglia. Colour Doppler imaging demonstrated blood flow within the echogenicities confirming the suspected diagnosis of

M. Ries; K.-H. Deeg; D. Wölfel; H. Ibel; B. Maier; G. Buheitel



Acute Infantile Gastroenteritis Associated with Human Enteric Viruses in Tunisia  

Microsoft Academic Search

This prospective study, conducted from January 2003 to June 2005, investigated the incidence and the clinical role of various enteric viruses responsible for infantile gastroenteritis in 632 Tunisian children presenting in dispensaries (380 children) or hospitalized (252 children) for acute diarrhea. At least one enteric virus was found in each of 276 samples (43.7%). A single pathogen was observed in

Khira Sdiri-Loulizi; Hakima Gharbi-Khelifi; Alexis de Rougemont; Slaheddine Chouchane; Nabil Sakly; Katia Ambert-Balay; Mouna Hassine; Mohamed Neji Guediche; Mahjoub Aouni; Pierre Pothier



Molecular genetics of infantile-onset retinal dystrophies  

Microsoft Academic Search

IntroductionOver the last decade there have been major advances in our understanding of the molecular pathology of inherited retinal dystrophies.DiscussionThis paper reviews recent advances in the identification of genetic mutations underlying infantile-onset inherited retinal disorders and considers how this knowledge may lead to novel therapeutic approaches.

P Moradi; A T Moore



Causes of infantile autism: Some considerations from recent research  

Microsoft Academic Search

Experimental, clinical, and longitudinal studies of infantile autism are reviewed and the evidence with respect to different views on the causation of the condition is considered. Several independent investigations have shown the presence of a severe, extensive defect in language comprehension, in control functions associated with language, and with the processing of symbolic or sequenced information. Circumstantial evidence suggests that

Michael Rutter; Lawrence Bartak



Infantile Parkinsonism-dystonia and elevated dopamine metabolites in CSF  

Microsoft Academic Search

Two girls and one boy are described, with severe infantile parkinsonism-dystonia. This syndrome is usually caused by endogenous dopamine deficiency but in these patients was associated with elevated dopamine metabolites in CSF and an unusual eye movement disorder: ocular flutter together with saccade initiation failure. Pyramidal tract signs also emerged in the course of the disease in two patients. This

B. Assmann; R. O. Robinson; R. Surtees; C. Brautigam; S. J. Heales; R. A. Wevers; J. Zschocke; K. Hyland; R. K. Sharma; G. F. Hoffmann



Bone marrow transplantation for infantile ceramidase deficiency (Farber disease)  

Microsoft Academic Search

Infantile ceramidase deficiency (Farber disease) is an uncommon, progressive lysosomal storage disease characterized by multiple ceramide-containing nodules (lipogranulomata) in the subcutaneous tissue and upper aerodigestive tract, painful periarticular swelling, psychomotor retardation, and varying degrees of ocular, pulmonary or hepatic involvement. Management of Farber disease has been limited to symptomatic supportive care, and few affected infants survive beyond 5 years of

AM Yeager; K Armfield Uhas; CD Coles; PC Davis; WL Krause; HW Moser



Development of infantile rat ovaries autotransplanted after cryopreservation by vitrification  

Microsoft Academic Search

We cryopreserved infantile rat ovaries by vitrification and assessed their viability by autotransplantation. Hemilateral ovarian transplantation was performed on rats on postnatal Days 10 to 12. The left ovary of each rat was dissected out, cryopreserved by vitrification using a modified vitrification solution (VS1), and then autotransplanted under the capsule of the right kidney. The right ovary of each rat

M. Sugimoto; S. Maeda; N. Manabe; H. Miyamoto



Part One: Infantile Spasms--The New Consensus  

ERIC Educational Resources Information Center

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…

Pellock, John



Infantile multiple system atrophy with cytoplasmic and intranuclear glioneuronal inclusions  

Microsoft Academic Search

This report presents a case of infantile multiple system atrophy with probably autosomal recessive inheritance. The female patient developed generalized muscular hypotonia, myoclonias and tonic-clonic seizures at the age of 8 months, followed by gradual development of choreoathetotic hyperkinesia and increasing psychomotor retardation. Metabolic disease was ruled out and the child died of aspiration pneumonia at the age of 5

M. Bergmann; K. Kuchelmeister; F. Gullotta; B. Kryne-Kubat; E. Burwinkel; K. Harms



Orbital masses: CT and MRI of common vascular lesions, benign tumors, and malignancies.  


A wide variety of space occupying lesions may be encountered in the orbit. CT and MR imaging frequently help confirm the presence of a mass and define its extent. Characteristic imaging features may help distinguish among lesions that have overlapping clinical presentations. This review focuses on some of the common orbital masses. Common vascular lesions that are reviewed include: capillary (infantile) hemangioma, cavernous hemangioma (solitary encapsulated venous-lymphatic malformation), and lymphangioma (venous-lymphatic malformation). Benign tumors that are reviewed include: optic nerve sheath meningioma, schwannoma, and neurofibroma. Malignancies that are reviewed include: lymphoma, metastasis, rhabdomyosarcoma, and optic glioma. Key imaging features that guide radiological diagnosis are discussed and illustrated. PMID:23961022

Khan, Sarah N; Sepahdari, Ali R



Orbital masses: CT and MRI of common vascular lesions, benign tumors, and malignancies  

PubMed Central

A wide variety of space occupying lesions may be encountered in the orbit. CT and MR imaging frequently help confirm the presence of a mass and define its extent. Characteristic imaging features may help distinguish among lesions that have overlapping clinical presentations. This review focuses on some of the common orbital masses. Common vascular lesions that are reviewed include: capillary (infantile) hemangioma, cavernous hemangioma (solitary encapsulated venous-lymphatic malformation), and lymphangioma (venous-lymphatic malformation). Benign tumors that are reviewed include: optic nerve sheath meningioma, schwannoma, and neurofibroma. Malignancies that are reviewed include: lymphoma, metastasis, rhabdomyosarcoma, and optic glioma. Key imaging features that guide radiological diagnosis are discussed and illustrated.

Khan, Sarah N.; Sepahdari, Ali R.



Bronchoalveolar Lavage in Malignancy  

Microsoft Academic Search

Bronchoalveolar lavage is a useful diagnostic tool in diffuse or disseminated lung malignancies that do not involve the bronchial structures visible by endoscopy. The neoplastic histotype and the intraparenchymal neoplastic growth pattern are good pre- dictors for diagnostic yield; adenocarcinoma, and tumors with lymphangitic or lepidic growth patterns more easily diagnosed by bronchoalveolar lavage; in these cases the diagnostic yield

Venerino Poletti; Giovanni Poletti; Bruno Murer; Luca Saragoni; Marco Chilosi



[Malignant peritoneal mesothelioma].  


Mesothelioma is a neoplasm originating from the mesothelial surface lining cells of the serous human cavities. It may involve the pleura, less frequently the peritoneum rarely, the pericardium, the tunica vaginalis testis and ovarian epithelium. Asbestos has been widely used in industry. A causal relationship between asbestos exposure and pleural, peritoneal and pericardial malign mesothelioma was suggested, the risk of cancer being correlated to cumulate exposure. Studies from National Cancer Institute, USA, show that the malignant mesothelioma is a rare and aggressive asbestos related malignancy. The symptomatology is insidious and poses difficult problems in diagnosis and treatment. This paper presents the case of a 59 year old patient with malignant peritoneal mesothelioma who worked almost 40 years as an electrician, exposed to asbestos fibers. He was hospitalized for important weight loss, abdominal pain and tiredness being diagnosed after imaging tests with a giant tumor, localized at the abdominal upper level, which seems to originate from the spleen's superior pole. During surgery we discovered a tumor with cystic parts, intense vascularized, which turn to be adherent in the upper side to the lower face of the left midriff cupola, to the spleen superior pole and 1/3 middle level of the great gastric curve. It was performed surgical ablation of the tumor, splenectomy with favorable postoperative evolution, the patient being now under chemotherapy treatment. PMID:17283842

Scripcariu, V; Dajbog, Elena; Lefter, L; Ferariu, D; Pricop, Adriana; Grigora?, M; Dragomir, Cr



Malignant adnexal neoplasms  

Microsoft Academic Search

Malignant cutaneous adnexal neoplasms are one of the most challenging areas of dermatopathology. Tumors of the pilosebaceous apparatus can occur as single-lineage neoplasms or may manifest as complex proliferations with multilineal differentiation patterns including not only the germinative component of the hair bulb, the inner or outer root sheath epithelium and the sebaceous gland and duct, but also the sweat

A Neil Crowson; Cynthia M Magro; Martin C Mihm



Malignant tumors of childhood  

SciTech Connect

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.

Brooks, B.J.



Treatment for Malignant Ascites

In this trial, researchers will randomly assign patients with malignant ascites to receive either octreotide or a placebo once a month for up to two years. The investigators will see whether octreotide can delay, or even eliminate, the need for paracentesis and assess side effects and quality of life of patients undergoing this treatment.


Malignant pleural diseases.  


The incidence of malignant pleural effusions has been increasing over the last few decades (mainly due to the absolute increase in several types of cancers, especially those of lung and breast origin) and they account for up to 50% of the exudates in many clinical series. Although pleural malignancies are thought to present most frequently with a pleural effusion, several autopsy series, including the current one, found a pleural effusion present in little more than half of the cases of malignant pleural involvement (55% in this series). Thus, many pleural malignancies without effusion might pass unnoticed in clinical practice, especially in metastatic disease. Primary malignancies of the pleura (mesotheliomas) are associated with asbestos exposure in about two-thirds of cases, and they frequently present with chest pain, sometimes associated with a pleural effusion. Benign pleural plaques can coexist with malignant mesothelioma, and this association should be suspected when long-standing plaques change in shape or size over the years, and especially if chest pain develops in a previously asymptomatic patient. Metastatic pleural involvement is much more frequent than mesotheliomas, and its most frequent mechanism is the vascular spreading of tumour cells from distant organs to the lungs, and on to the visceral and parietal pleura. The visceral pleura was involved in up to 87% of the current metastatic cases, whereas the parietal zone in only 47% of the autopsy series. The diagnostic work-up lies in cytology, whose average yield is approximately 50%, and a biopsy technique (either by blind needle biopsy or thoracoscopy) is recommended when the effusion persists, for > 2 weeks, and the first cytology has been negative. Thoracoscopy has the additional advantage of allowing pleurodesis with talc poudrage if clear tumour lesions are found in the pleura. In cases of malignant effusion which are not sensitive to chemotherapy, pleurodesis is the treatment of choice for palliation of symptoms, and talc is the most effective agent. It can be used either in suspension ("slurry") or in dry aerosolized form ("talc poudrage"), but it seems that this last technique achieves the best effects. However, it requires thoracoscopy for a proper application, and this is its main drawback when that technique is not readily available. PMID:10786419

Rodriguez-Panadero, F



Malignant lymphoma involving the penis following malignant pleural mesothelioma.  


A 74-year-old man who had been diagnosed with malignant mesothelioma developed malignant lymphoma of B-cell origin involving the penis. He had a history of occupational exposure to asbestos as a construction worker. The association of malignant mesothelioma with lymphoma is rare, and the possibility of asbestos exposure as a common etiology is discussed. The intense stimulation of B lymphocytes and decreased T lymphocyte activity in asbestos-exposed populations may result in development of B-cell malignancies. Though the relationship between asbestos exposure and malignant mesothelioma is firmly established, the relationship between asbestos exposure and lymphoma remains to be investigated. PMID:9372333

Takabe, K; Tsukada, Y; Shimizu, T; Takagiwa, J; Hirayama, M; Nakayama, M; Miura, H; Akabane, H; Takayama, S; Aida, S; Kimura, Y



Malignancy in Neurofibromatosis Type 1  

Microsoft Academic Search

Neurofibromatosis type 1 (NF1) represents a major risk factor for development of malignancy, particularly malignant peripheral nerve sheath tumors (MPNST), optic gliomas, other gliomas, and leukemias. The oncol- ogist will see NF1 patients referred for treatment of malignancy, and should be alert to the possibility of undiagnosed NF1 among patients with cancer. Brain tumors tend to have a more indolent



Hematologic malignancies and thrombosis.  


Patients with hematologic malignancies have an increased risk of venous thromboembolism (VTE), particularly at diagnosis and during the treatment with chemotherapy, asparaginase or immunomodulatory drugs (IMiDs). A disease-dependent hypercoagulable condition associated with other risk factors like drugs, central venous catheter (CVC), immobility and infections are responsible for this high VTE rate. Thrombotic complications have a significant impact on morbidity and in some cases also on mortality of patients with onco-hematologic diseases, therefore thromboprophylaxis to prevent VTE in this setting is needed. However, thrombocytopenia and hemorrhagic complications pone many difficulties in the management of an anticoagulant or antiaggregant treatment in these patients. Recommendations from current guidelines are limited to multiple myeloma patients treated with thalidomide or lenalidomide associated with dexamethasone or chemotherapy, but hematological clinical departments should implement a policy for prevention and treatment of thromboembolic complications in hematologic malignancies. PMID:22197450

Elice, F; Rodeghiero, F



Lymphoscintigraphy in malignant melanoma  

SciTech Connect

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.

Berman, C.G.; Norman, J.; Cruse, C.W.; Reintgen, D.S.; Clark, R.A. (Department of Radiology, H. Lee Moffitt Cancer Center, Tampa, FL (United States))



Hyaluronan in human malignancies  

SciTech Connect

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.

Sironen, R.K. [Institute of Clinical Medicine, Pathology and Forensic Medicine, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio (Finland) [Institute of Clinical Medicine, Pathology and Forensic Medicine, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio (Finland); Department of Pathology, Kuopio University Hospital, P.O. Box 1777, FI-70211 Kuopio (Finland); Tammi, M.; Tammi, R. [Institute of Biomedicine, Anatomy, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio (Finland)] [Institute of Biomedicine, Anatomy, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio (Finland); Auvinen, P.K. [Department of Oncology, Kuopio University Hospital, P.O. Box 1777, FI-70211 Kuopio (Finland)] [Department of Oncology, Kuopio University Hospital, P.O. Box 1777, FI-70211 Kuopio (Finland); Anttila, M. [Institute of Clinical Medicine, Pathology and Forensic Medicine, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio (Finland) [Institute of Clinical Medicine, Pathology and Forensic Medicine, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio (Finland); Department of Gynecology and Obstetrics, Kuopio University Hospital, P.O. Box 1777, FI-70211 Kuopio (Finland); Kosma, V-M., E-mail: [Institute of Clinical Medicine, Pathology and Forensic Medicine, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio (Finland); Department of Pathology, Kuopio University Hospital, P.O. Box 1777, FI-70211 Kuopio (Finland)



Malignant insulinoma in childhood.  


Pancreatic tumors constitute a rare surgical problem in infancy and childhood. Insulinomas are rare in all age groups with an estimated incidence of one per 250,000 person-years and even rarer in childhood. We report a 10 year-old girl with malignant insulinoma. The presenting symptom was hypoglycemic attacks. Laboratory investigation demonstrated that the hypoglycemia was due to hyperinsulinism. MRI of the abdomen revealed a mass at the tail of the pancreas. Distal pancreatectomy with splenectomy was performed. Histological examination showed malignant insulinoma with peripancreatic lymph node metastases. One month later abdominal MRI revealed the existence of multiple small metastatic foci in the liver, which were confirmed by In111 octreoscan. Treatment with octreotide was started and the disease is stable after 12 months of therapy. PMID:16789643

Karachaliou, Feneli; Vlachopapadopoulou, Elpis; Kaldrymidis, Philipos; Simatos, George; Zacharea, Maria; Spanidou-Karvouni, Erini; Michalacos, Stefanos; Voros, Dionyssios



The malignant social network  

PubMed Central

Tumors contain a vastly complicated cellular network that relies on local communication to execute malignant programs. The molecular cues that are involved in cell-cell adhesion orchestrate large-scale tumor behaviors such as proliferation and invasion. We have recently begun to appreciate that many tumors contain a high degree of cellular heterogeneity and are organized in a cellular hierarchy, with a cancer stem cell (CSC) population identified at the apex in multiple cancer types. CSCs reside in unique microenvironments or niches that are responsible for directing their behavior through cellular interactions between CSCs and stromal cells, generating a malignant social network. Identifying cell-cell adhesion mechanisms in this network has implications for the basic understanding of tumorigenesis and the development of more effective therapies. In this review, we will discuss our current understanding of cell-cell adhesion mechanisms used by CSCs and how these local interactions have global consequences for tumor biology.

Hale, James S.; Li, Meizhang; Lathia, Justin D.



Nicotinamide Phosphoribosyltransferase in Malignancy  

PubMed Central

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.

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



Microbiome and Malignancy  

PubMed Central

Current knowledge is insufficient to explain why only a proportion of individuals exposed to environmental carcinogens or carrying a genetic predisposition to cancer develop disease. Clearly, other factors must be important and one such element that has recently received attention is the human microbiome, the residential microbes including Bacteria, Archaea, Eukaryotes, and viruses that colonize humans. Here, we review principles and paradigms of microbiome-related malignancy, as illustrated by three specific microbial-host interactions. We review the effects of the microbiota on local and adjacent-neoplasia, present the estrobolome model of distant effects, and discuss the complex interactions with a latent virus leading to malignancy. These are separate facets of a complex biology interfacing all the microbial species we harbor from birth onward toward early reproductive success and eventual senescence.

Plottel, Claudia S.; Blaser, Martin J.



Malignant Peritoneal Mesothelioma  

Microsoft Academic Search

Malignant peritoneal mesothelioma (MPM) is an incurable disease. It represents approximately 15% of all mesotheliomas and\\u000a has a male predominance. It has a known relationship to asbestos, but most patients present with no known history of exposure.\\u000a Simian virus 40 (SV40) exposure is potentially another risk factor, although the relationship is not entirely supported. Patients\\u000a usually present with vague symptoms.

David P. Mangiameli; Steven K. Libutti; James F. Pingpank; H. Richard Alexander


Malignant spinal cord compression  

Microsoft Academic Search

Opinion statement  Malignant spinal cord compression is one of the most dreaded complications of cancer. If untreated, it can lead to worsening\\u000a neurologic function culminating in paralysis and sphincter incontinence. The most challenging aspect in the management of\\u000a this complication is early diagnosis because the single most important factor determining outcome is the level of neurologic\\u000a function at initiation of therapy.

Madhuri Yalamanchili; Glenn J. Lesser



Pedunculated malignant melanoma.  


A woman had a primary pedunculated malignant melanoma. This is a rare form of presentation and may result in clinical confusion with seborrheic keratosis, fibroepithelial papilloma, or granuloma pyogenicum. The aggressive nature of the lesion was indicated by the presence of erosion and bleeding. Though the tumor cells were present only in the pedunculated mass, it had metastasized to regional lymph nodes at the time of surgery. PMID:1137420

Niven, J; Lubin, J



Asbestos-related malignancy  

SciTech Connect

Asbestos-associated malignancies have received significant attention in the lay and medical literature because of the increasing frequency of two asbestos-associated tumors, lung carcinoma and mesothelioma; the wide distribution of asbestos; its status as a prototype environmental carcinogen; and the many recent legal compensation proceedings, for which medical testimony has been required. The understanding of asbestos-associated carcinogenesis has increased through study of animal models, human epidemiology, and, recently, the application of modern molecular biological techniques. However, the detailed mechanisms of carcinogenesis remain unknown. A wide variety of malignancies have been associated with asbestos, although the strongest evidence for a causal association is confined to lung cancer and mesothelioma. Epidemiological studies have provided evidence that both the type of asbestos fiber and the industry in which the exposure occurs may affect the rates of asbestos-associated cancers. It has been shown that asbestos exerts a carcinogenic effect independent of exposure to cigarette smoking that, for lung cancers, is synergistically enhanced by smoking. Other questions remain controversial, such as whether pulmonary fibrosis necessarily precedes asbestos-associated lung cancer and whether some threshold level of exposure to asbestos (including low-dose exposures that may occur in asbestos-associated public buildings) may be safe. Mesothelioma, the most closely asbestos-associated malignancy, has a dismal natural history and has been highly resistant to therapy. However, investigational multi-modality therapy may offer benefit to some patients. 179 references.

Talcott, J.A.; Antman, K.H.



Simultaneous onset of infantile spasms in monozygotic twins.  


The clinical, electroencephalographic, and genetic findings are reported for three pairs of monozygotic twins who developed infantile spasms in their first year. In all three pairs, the spasms started on the same day in each member of the pair. Neither sequencing of the ARX and CDKL5 (alias STK9) genes nor array comparative genomic hybridization assessment revealed any abnormalities. The long-term outcome was poor in all twins, although with different severity in individual pairs. These findings suggest that genes other than those currently known likely play a role in predisposition to infantile spasms, and that genetic susceptibility is linked to a variable phenotypic expression, ranging from quite benign to very severe, in monozygotic twins with no other apparent risk factors. PMID:20610124

Coppola, Giangennaro; Grosso, Salvatore; Verrotti, Alberto; D'Aniello, Alfredo; Pascotto, Antonio



New Treatments for Infantile and Other Forms of Nystagmus  

Microsoft Academic Search

Our objective was to translate the past 40 years of infantile nystagmus syndrome (INS) research (i.e., ocular motor recording and control-systems analysis) into a therapeutic approach. Our eye movement recordings use infrared reflection, mag­ netic search coil, and high-speed digital video sys­ tems. Each eye was calibrated during monocular fixation (fellow-eye occluded). We analyzed and displayed all data using software



Infantile hypertrophic pyloric stenosis after prenatal exposure to thalidomide  

Microsoft Academic Search

In a retrospective study of 832 cases of thalidomide embryopathy (ThE) between October 1, 1959 and July 31, 1962, a highly significant accumulation of cases with infantile hypertrophic pyloric stenosis (IHPS) was registrated. Clinical course, X-ray and surgical findings and the sex ratio (male preponderance) were identical to IHPS occurring spontaneously. In the order of frequency of defects in ThE,

K. H. Schäfer; M. Kramer



Assessment of infantile mineral imbalances in autism spectrum disorders (ASDs).  


The interactions between genes and the environment are now regarded as the most probable explanation for autism. In this review, we summarize the results of a metallomics study in which scalp hair concentrations of 26 trace elements were examined for 1,967 autistic children (1,553 males and 414 females aged 0-15 years-old), and discuss recent advances in our understanding of epigenetic roles of infantile mineral imbalances in the pathogenesis of autism. In the 1,967 subjects, 584 (29.7%) and 347 (17.6%) were found deficient in zinc and magnesium, respectively, and the incidence rate of zinc deficiency was estimated at 43.5% in male and 52.5% in female infantile subjects aged 0-3 years-old. In contrast, 339 (17.2%), 168 (8.5%) and 94 (4.8%) individuals were found to suffer from high burdens of aluminum, cadmium and lead, respectively, and 2.8% or less from mercury and arsenic. High toxic metal burdens were more frequently observed in the infants aged 0-3 years-old, whose incidence rates were 20.6%, 12.1%, 7.5%, 3.2% and 2.3% for aluminum, cadmium, lead, arsenic and mercury, respectively. These findings suggest that infantile zinc- and magnesium-deficiency and/or toxic metal burdens may be critical and induce epigenetic alterations in the genes and genetic regulation mechanisms of neurodevelopment in the autistic children, and demonstrate that a time factor "infantile window" is also critical for neurodevelopment and probably for therapy. Thus, early metallomics analysis may lead to early screening/estimation and treatment/prevention for the autistic neurodevelopment disorders. PMID:24284360

Yasuda, Hiroshi; Tsutsui, Toyoharu



New insights into the pathogenesis of infantile pyloric stenosis  

Microsoft Academic Search

Infantile hypertrophic pyloric stenosis (IHPS) is the most common surgical cause of vomiting in infants. Despite numerous\\u000a hypotheses, the aetiopathogenesis of IHPS is not fully understood. Genetic, extrinsic and hormonal factors have been implicated\\u000a in the pathogenesis of the disease. Furthermore, abnormalities of various components of the pyloric muscle such as smooth\\u000a muscle cells, growth factors, extracellular matrix elements, nerve

Christina Panteli



Oropharyngeal Dysphagia in Infants and Children with Infantile Pompe Disease  

Microsoft Academic Search

Pompe disease is a rare genetic progressive neuromuscular disorder. The most severe form, infantile Pompe disease, has historically\\u000a resulted in early mortality, most commonly due to cardiorespiratory failure. Treatment with enzyme replacement therapy (ERT)\\u000a using alglucosidase alfa (Myozyme®) has extended the lifespan of individuals with this disease. With the introduction of ERT and the resultant improved survival,\\u000a dysphagia is being

Harrison N. Jones; Carolyn W. Muller; Min Lin; Suhrad G. Banugaria; Laura E. Case; Jennifer S. Li; Gwendolyn O’Grady; James H. Heller; Priya S. Kishnani



A comparative demographicand socioeconomic study of spasmus nutansand infantile nystagmus  

Microsoft Academic Search

PURPOSE: To compare the demographic and socioeconomic background of patients with spasmus nutans (SN) and patients with idiopathic infantile nystagmus (IIN).METHODS: This study was performed according to an observational case-control design. Parents or guardians of 23 patients with SN and 24 patients with IIN completed a 28-point questionnaire on demographic, socioeconomic, behavioral, personal, and family history. Mann-Whitney U tests were

Sheryl S. Wizow; Robert D. Reinecke; Mihai Bocarnea; Irene Gottlob



Linkage analysis of late-infantile neuronal ceroid-lipofuscinosis  

SciTech Connect

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.

Sharp, J.; Wheeler, R.B.; Jaervelae, I. [Rayne Institute, London (United Kingdom)] [and others



Acupuncture in Practice: Investigating Acupuncturists' Approach to Treating Infantile Colic  

PubMed Central

Infantile colic is common, but no safe and effective conventional treatment exists. The use of acupuncture has increased despite weak evidence. This practitioner survey explores and discusses how infantile colic is regarded and treated in Traditional Chinese Medicine (TCM). The study is based on personal communication with 24 acupuncturists from nine countries. These acupuncturists specialize in pediatric acupuncture and represent different styles of acupuncture. Their experiences are discussed and related to relevant books and articles. Informants claimed good results when treating infants with colic. The TCM patterns commonly described by informants matched the textbooks to a great extent. The most common syndromes were “stagnation of food” and “Spleen Qi Xu.” Regarding treatment, some informants followed the teachers' and the textbook authors' advice on differentiated treatment according to syndrome. The points used most often were LI4, ST36, and Sifeng. Other informants treated all infants alike in one single point, LI4. The results demonstrate the diversity of TCM. The use of acupuncture for infantile colic presents an interesting option, but further research is needed in order to optimize the effects and protect infants from unnecessary or less effective treatment.



Stereoacuity Outcomes Following Treatment of Infantile and Accommodative Esotropia  

PubMed Central

Purpose To review what is known about the normal maturation of stereoacuity, the stereoacuity deficits associated with infantile and accommodative esotropia, the rationale for making improved stereoacuity a goal of treatment, and strategies for improving stereoacuity outcomes. Methods Studies of stereoacuity maturation during normal development, studies of stereoacuity outcomes following treatment for infantile and accommodative esotropia, and studies of primate models of esotropia are reviewed. Results Stereoacuity maturation normally proceeds rapidly during the first year of life. Infantile and accommodative esotropia are associated with profound and permanent disruption of stereopsis. While rehabilitation of stereoacuity following treatment of esotropia remains a challenge, even the achievement of subnormal stereoacuity may have real benefits to the child. Conclusions Some abnormalities in stereoacuity may exist before the onset of esotropia, but others may result directly from abnormal binocular experience. Several strategies for improving stereoacuity outcomes in esotropia are currently under active investigation. Improved stereoacuity outcomes are associated with better long term stability of alignment, reduced risk for and/or severity of amblyopia, improved achievement of sensorimotor developmental milestones, better reading ability, and improved long-term quality of life.

Birch, Eileen E.; Wang, Jingyun



Pleural malignancies including mesothelioma.  


Malignant mesothelioma is caused almost exclusively by occupational exposure to asbestos. During the past few years, however, increasing evidence has mounted that background exposure to asbestos could be sufficient to cause mesothelioma. Treatment of malignant mesothelioma remains a big problem. Some new approaches are on their way, and the most exciting ones are local immunotherapy in very early cases. Some success has been reported with local interferon treatment. As for treatment of metastatic pleural disease, the main purpose is symptomatic relief of dyspnea caused by fluid accumulation. The best way to achieve a lasting palliation is pleurodesis, and the most common way to do this, is by chemical means. The drug of choice in the United States has for many years been tetracycline, but since injectable tetracycline is no longer available, some substitute must be found. The substance that will "win" is not yet clear, but the two leading contestants are talc and doxycycline. Bleomycin also has its supporters, and a dark horse is quinacrine, which although not easily available in the United States, has been used in many European centers for decades. PMID:9363074

Hillerdal, G



Radioimmunotherapy of malignancies  

SciTech Connect

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.

Reilly, R.M. (Division of Nuclear Medicine, Toronto Hospital, Ontario (Canada))



Metastatic malignant biliary obstruction.  


Jaundice due to metastatic tumor involving the extra-hepatic bile ducts is uncommon, and thus, the management of this problem is not standardized. Retrospective analysis of all patients admitted to University Hospitals of Cleveland with malignant biliary obstruction was thus undertaken to identify the incidence, origin, management, and outcome of these metastatic tumors. During a 5-year period, 56 patients with jaundice secondary to biliary, pancreatic, ampullary, or metastatic tumors were identified. Of these, 12 (21%) represented a distant malignant process metastatic to the porta hepatis. Sites of origin were diverse: lymphoma, 2; breast, 3; colon, 2; and 1 each with Hodgkin's, lung, ovary endometrium, and melanoma. Patients ranged in age from 31 to 90 years (mean: 60). Surgical intervention was undertaken in only two patients (cholecystojejunostomy, 1; transhepatic U-tube stenting, 1). The remainder were managed as follows: no procedure, 3 (25%); percutaneous stenting, 5 (42%); and radiation only, 2 (17%). Mortality was as follows: 5 of 12 (42%) died within 30 days and 8 of 12 (67%) within 60 days. The only survivors beyond 60 days were the patients with Hodgkin's (1 of 1), lymphoma (1 of 2), breast (1 of 3) and melanoma (1 of 1). Ten of the patients had obvious extensive metastatic disease, which would explain the poor outcome. Analysis of this data indicates that overall survival is dismal and palliative, nonoperative methods to manage the jaundice should be considered. PMID:3605855

Stellato, T A; Zollinger, R M; Shuck, J M



Prostate Metastasis of Malignant Melanoma  

PubMed Central

Metastatic malignant melanoma of the prostate is extremely rare in clinical practice, and only one case has been reported in the English literature in the past 30 years. We report a case of malignant melanoma that metastasized to the prostate and review the current literature. A 50-year-old man with a history of malignant melanoma metastasis to the left axilla, which was excised 3 years ago, presented with lower urinary tract symptoms and gross hematuria. He underwent cystoscopy and transurethral resection of the prostate. The pathological examination showed metastatic malignant melanoma of the prostate gland. The patient died 6 months after the transurethral resection.

Selimoglu, Ahmet; Horuz, Rahim; Akca, Oktay; Albayrak, Selami



Mental and behavioural outcome of infantile epilepsy treated by vigabatrin in tuberous sclerosis patients  

Microsoft Academic Search

Vigabatrin (VGB) has demonstrated high efficacy in infantile spasms (IS) due to tuberous sclerosis. Our first objective was to evaluate the cognitive long term effect outcome of children whose refractory spasms definitely disappeared when VGB was given as an add on drug. Our second objective was to determine the response of generalized epilepsy (infantile spasms) compared to partial epilepsy on

I. Jambaquea; C. Chiron; C. Dumas; J. Mumford; O. Dulac



Infantile hemangiomas are arrested in an early developmental vascular differentiation state  

Microsoft Academic Search

Infantile hemangiomas, the most common tumors of infancy, are vascular tumors characterized by rapid proliferation of endothelial cells during the first few months of postnatal life followed by slow spontaneous involution, whose molecular pathogenesis remains unclear. The recent identification of developmental expression of vascular lineage-specific markers prompted us to characterize infantile hemangiomas for the expression of lymphatic endothelial hyaluronan receptor-1

Soheil S Dadras; Paula E North; Jennifer Bertoncini; Martin C Mihm; Michael Detmar



Epidemiology of infantile autism in southern Ibaraki, Japan: Differences in prevalence in birth cohorts  

Microsoft Academic Search

Infantile autism was diagnosed by DSM-III criteria in 132 children (26 girls) who were outpatients of the Tsuchiura Child Guidance Center during the years 1977–1985. The children, all Japanese except for one Laotian boy born in Laos, were classified according to year and month of birth. The prevalence rate of infantile autism in southern Ibaraki, Japan, within the birth cohort

Yoko Tanoue; Susumu Oda; Fusao Asano; Kazuko Kawashima



Malignant primary cardiac tumours  

PubMed Central

OBJECTIVES Management of malignant tumours of the heart remains a poorly investigated clinical area due to the scarcity of presentations. The purpose of this series and review is to present an outline of the management emphasized by our personal experience in a regional cardiothoracic centre. METHODS We reviewed all cases presenting with primary cardiac tumours in our institution within the last 10 years, looking at presentation, management and outcomes. RESULTS Of these, the records of 3 patients, who attended the Royal Victoria Hospital in Belfast and were treated for a cardiac sarcoma, were fully evaluated. A review of current literature was conducted through a search of Pubmed and Medline databases. A review of the presentation of these patients and the generally accepted management deterioration of patients diagnosed with cardiac sarcoma is discussed. CONCLUSIONS With reference to our case series, we want to draw attention to the rapid deteriation of these patients following presentation.

Burnside, Nathan; MacGowan, Simon W.



Temozolomide in malignant glioma  

PubMed Central

Glioblastoma multiforme WHO grade IV (GBM) is the most aggressive malignant glioma and the most frequent primary tumor of the central nervous system. The median survival of newly diagnosed GBM patients was between 9 to 12 months prior to treatment with temozolomide being introduced. Primary resection that is as complete as possible is recommended for malignant glioma. Conventional fractionated irradiation 55 to 60 gy with concomitant temozolomide followed by standard temozolomide 6 cycles (5/28) (EORTC/NCIC-regime published by R Stupp in 2005) is the standard of care for newly diagnosed GBM after surgery, independent of the methylation status of the MGM-T gene promoter. Age is no contraindication for treatment with temozolomide, although comorbidity and performance status have to be considered. For temozolomide naive GBM and astrocytoma grade III patients with disease progression, temozolomide is still the treatment of choice outside of clinical studies. A general consensus regarding the schedule of choice has not yet been achieved; so far the 5 out of 28 days regimen (5/28) is the standard of care in most countries. Patients with disease progression after standard temozolomide (5/28) are candidates for clinical studies. Outside of clinical studies, dose-dense (7/7), prolonged (21/28), or metronomic (28/28) temozolomide, or alternatively a nitrosourea-based regimen can be an option. The excellent toxicity profile of temozolomide allows for various combinations with antitumor agents. None of these combinations, however, have been demonstrated to be statistically significantly superior compared to temozolomide alone. The role of lower dosed, dose-dense, or continuous regimen with or without drug combination and the role of temozolomide for newly diagnosed astrocytoma grade III and low grade glioma still has to be determined.

Dresemann, Gregor



Case Report: Malignant Struma Ovarii  

Microsoft Academic Search

Struma ovarii are specialized teratomas consisting of thyroid tissue with various microscopic features, ranging from benign to malignant. We report a rare form of malignant struma ovarii, composed exclusively of a follicular variant of papillary thyroid carcinoma with capsular invasion, which occurred in a 65-yr-old woman. (received 2 July 2003; accepted 3 October 2003)

Maria D. Navarro; Mary Aldrene; L. Tan; John L. Lovecchio; Steven I. Hajdu


[Management of malignant pleural effusions].  


Malignant pleural effusions with dyspnoea as their most common presenting symptom are a frequent clinical problem in patients with neoplastic disease. Lung carcinoma is the leading cause, followed by breast carcinoma and malignant lymphoma. The frequency of malignant mesothelioma is increasing in industrialized countries. In this overview, which is based on the ERS/ATS Statement 2001, the diagnostic approach, the differential diagnosis including causes of paramalignant effusions, as well as the therapeutic possibilities are described. Pleurodesis is the most important therapeutic modality, today preferably via thoracoscopic talc poudrage. Alternative local and systemic treatment options are discussed in detail. A special emphasis is put on the epidemiology, diagnosis, treatment, and prognosis of malignant effusions in patients with lung and breast carcinomas, and with lymphomas. Finally, open questions are listed which need future research, which will hopefully improve the treatment and prognosis of malignant pleural effusions. PMID:15724226

Loddenkemper, R



Recent results of treatment of infantile hypertrophic pyloric stenosis.  

PubMed Central

During the five year period December 1980 to November 1985, 106 infants with hypertrophic pyloric stenosis were treated. There were no operative deaths, but two late deaths occurred from associated abnormalities. The combination of preoperative rehydration, skilled anaesthesia, and the use of the Fredet-Ramstedt operation (pyloromyotomy) have virtually eliminated mortality from uncomplicated infantile hypertrophic pyloric stenosis. The most common complications were gastro-oesophageal reflux in 11 (11%), perforation of the duodenal fornix in nine (8%), and wound infection in five (5%); no wound dehisced.

Zeidan, B; Wyatt, J; Mackersie, A; Brereton, R J



Infantile hypertrophic pyloric stenosis: where should it be treated?  

PubMed Central

A retrospective analysis in the form of an audit into the management of infantile hypertrophic pyloric stenosis in a district general hospital has revealed that the results are equivalent to that of published data from specialised units. It is stressed in this study that close co-operation has to be maintained between paediatricians and surgeons in the care of these infants. The diagnosis can be made on clinical grounds in the majority of cases. The operation has to be carried out by experienced surgeons and anaesthetists. The morbidity can be minimised under these circumstances and pyloromyotomy can be performed safely in a district general hospital.

Jahangiri, M.; Osborne, M. J.; Jayatunga, A. P.; Bradley, J. W.; Mitchenere, P.



Insidious peripheral neuropathy occurring under treatment in infantile MTHFR deficiency.  


5,10-Methylenetetrahydrofolate reductase (MTHFR) deficiency was diagnosed in a 1-month-old baby with signs of cerebral distress. Under a classic treatment using methionine supplementation, methyl donor (betaine) folinic acid, vitamin B(6) and vitamin B(12), the neuromotor development was satisfactory. At 15 years of age, however, despite no clear modification of the biochemical markers in body fluids, she developed a clinically overt peripheral axonal neuropathy. Only partial clinical improvement was obtained after reinforcement of betaine doses. Surveillance of the peripheral nerve is indicated in MTHFR deficiency, including in the infantile form with a good therapeutic compliance. PMID:19697151

Chaabene-Masmoudi, A; Mesrati, F; Zittoun, J; Landrieu, P



Disconnections in infantile-onset saccade initiation delay: a hypothesis.  


Infantile-onset saccade initiation delay (ISID), commonly known as congenital ocular motor apraxia, is characterized by difficulty in triggering horizontal volitional saccades. It typically presents with head thrusts in infancy and is often associated with developmental delay. Patients with ISID are reported to have abnormalities in various brain regions including the corpus callosum, brainstem, and cerebellum. We propose that ISID is caused by the disruption or disconnection of axons linking analogous brain regions involved in processing saccades across the two sides of the brain or bilateral damage to these regions. PMID:21059538

Salman, Michael S; Ikeda, Kristin M



Infantile systemic hyalinosis: A case report and review of literature.  


We report a case of infantile systemic hyalinosis in a 3.5-month-old male child born out of consanguineous marriage. He presented with multiple brownish raised lesions over bony prominences. He had also developed difficulty in movement of limbs and as a result developed severe flexion joint contractures. There was history of similar complaints in elder sibling who died at the age of 5 months due to repeated episodes of pneumonia. Skin biopsy from one of the papulonodular lesions showed increased amount of amorphous hyaline matrix, which was Periodic Acid Schiff positive with scattered fibroblasts. Though classical, we report this case for its rarity in western India. PMID:23130184

Madke, Bhushan; Kharkar, Vidya; Mahajan, Sunanda; Chikhalkar, Siddhi; Khopkar, Uday



Infantile Hepatic Hemangioendothelioma in Comparison with Hepatoblastoma in Children: Clinical and Ultrasound Features  

PubMed Central

Background Infantile hepatic hemangioendothelioma (IHH) and hepatoblastoma (HBL) are respectively the most common benign and malignant liver tumors in children. Objectives To study the clinical manifestations and the ultrasound features of the pediatric patients for distinguishing IHH from HBL. Patients and Methods Between 2002 and 2012, thirteen children with IHH and 38 children with HBL under the age of 10 years were included. We retrospectively reviewed the clinical and the ultrasound features of the two groups, especially including parameters as follows: age at diagnosis, gender, alpha-fetoprotein (AFP) elevation, venous involvement and Doppler ultrasound. Results Compared with HBL group, the age of IHH group was much younger (5.8 months vs. 35.1 months, P = 0.000), the AFP elevation was less likely to be detected in IHH group (23.1% vs. 89.5%, P = 0.000). Although the color flow were the same commonly observed (61.5% vs. 52.6%, P > 0.05), the spectral Doppler showed IHH was less likely to appear as arterial flow with resistance index (RI) > 0.7(12.5% vs. 75.0%, P < 0.05), characterized by arterial flow with RI < 0.7 and/or venous flow. Combined the clinical features including age (< 6 months) and normal AFP level yielded high capability in differential diagnosis, with sensitivity, specificity and Youden index of 77% (10/13), 95% (36/38), and 0.72, respectively. When combined clinical features (age and AFP) and spectral Doppler as the diagnostic criterion for distinguishing these cases with positive color flow signals, the sensitivity, specificity, accuracy and Youden Index were 88%, 95%, 89% and 0.83, respectively. Conclusions The clinical features are effective indicators for distinguishing IHH from HBL, and the spectral Doppler may be a useful adjunct parameter for differential diagnosis.

Pan, Fu-shun; Xu, Ming; Wang, Wei; Zhou, Lu-yao; Xie, Xiao-yan



Malignant eroticized countertransference.  


Gabbard (1994) divided the pathology of therapists, both male and female, who commit sexual boundary violations into those who are psychotic, those who are predatory psychopaths, those engaging in masochistic surrender, and those called "the lovesick therapist." Lovesick therapists are the most common type and manifest crucial narcissistic themes of "a desperate need for validation by their patients, a hunger to be loved and idealized, and a tendency to use patients to regulate their own self-esteem" (p. 127). Among the psychodynamic aspects of this curiously circumscribed area of loss of reality testing that makes it difficult for the therapist to see how self-destructive and harmful such enactment is, are an unconscious reenactment of incestuous longings, a misperception of the patient's wish for maternal nurturance as a sexual overture, enactments of rescue fantasies, a projected idealization of the self of the therapist, a confusion of the therapist's needs with the patient's needs, a fantasy that love is curative, acting out disavowed rage at the patient, or rage at an organization, an institute, or one's training analyst, a manic defense against mourning, a narcissistic fantasy that their sexual affair is an exception, insecurity regarding masculine identity, and assorted primitive preoedipal themes. Gabbard's (1991) erotized countertransference is one variety of what I have termed malignant eroticized countertransference. His variety is a development that occurs under the pressure of the patient's preemptive and compelling expressions of lust and love, the patient's erotic transference. But malignant eroticized countertransference can also occur without the patient having offered any such expressions; it can even occur on first meeting the patient when he or she walks into the office! This is akin to the romantic "love-at-first-sight" theme so favored in the movies and by novelists, but it is always pathological when it occurs in the therapeutic situation. Countertransference enactments are a creation between the patient and the therapist on a continuum from one pole, where the patient has just walked into the office and contributes almost nothing directly, to the other pole, where the therapist loses control of himself or herself as a response to the unbearable pressure of the patient's lust. In the treatment of malignant eroticized countertransference it seems clear from this discussion that every case should be evaluated psychodynamically and the treatment should be made to fit the patient, not the patient to the treatment. Each situation should be studied in psychodynamic depth without preconceptions based on generalizations or formulas. Therapists who are psychotic should of course be treated with antipsychotic drugs and usually should not be allowed to practice any further. Therapists who are psychopathic or sociopathic predators should certainly never be allowed to practice. Some of the individuals who are "lovesick," or, as I put it "love/lust obsessed," or those who have made a masochistic surrender to a sadistic destructive patient, are in need of reanalysis and have the potential to continue as effective therapists under careful supervision. Therapists like this do not deserve to be summarily dismissed from the profession but, like therapists who develop other serious neurotic problems, should receive appropriate help from us. PMID:9395991

Chessick, R D



[Malignant peritoneal mesothelioma].  


The peritoneal mesothelioma is a rare pathology with unspecific symptoms reason to be a difficult diagnosis. We report a case of a 58 year old man with diabetes mellitus type 2, arterial hypertension and smoking; without precedent of asbestos exposure. The patient presented a one month history characterized by progressive increase of the abdominal volume and sensation of fullness; three weeks later they added breathlessness and hyporexia. The patient was in regular general condition; he was not presenting hepatic stigmas, edema or adenomegalies. The examination of thorax and cardiovascular it was normal. The abdomen distended by ascites, not painful, liver and spleen not examined. Laboratory: Hemoglobin 11,9 gr/dl, WBC 6840/mm3 Bands 1 %, lymphocytes 10 %, platelets 620000/mm3, PT 12 seconds, PTT 34 seconds, glucose 158 mg/dl, BUN 20,5 mg/ dl, creatinine 1,2 mg/dl, proteins 6,1 gr/dl, albumin 2,6 gr/dl. LDH 316 U/l, beta2microglobulin 2,2 mg/l (0.83-1.15 mg/l). HBV and HCV negative. Ca 19.9, CEA, AFP and PSA negative. Hemocultive negative. Ascitic fluid: ADA 20,3 U/l, serum-ascitic albumin gradient (SAAG) 1,1. Leukocytes 2237 cells/mm3, PMN 6 %, lymphocytes 90 %, mesothelial cells 4 %, proteins 4,6 gr/dl, albumin 2,34 gr/dl, glucose 44 mg/dl, LDH 1918 U/l. Gram and cultive: negatives. BAAR and cultive: negative . Cytology: mesothelial cells with changes of type reagent, Block cell for tumour cells: negative. Abdominal US: increased peritoneum and abundant ascitic fluid. Thoracic-abdominal CT: left side pleural effusion, severe ascites with thick epyplon. Upper GI endoscopy: moderate gastritis. Colonoscopy: two small sessile polyps in sigmoid colon. The finds of the laparoscopy were interpreted like carcinomatosis or peritoneal tuberculosis. The report of the peritoneal biopsy was informed as suggestive of undifferentiated carcinoma; the reappraisal with inmunohystochemic (calretinin +,cytokeratin +, vimentin +) indicated malignant peritoneal mesothelioma, type epithelial. The evolution was torpid. The patient was transferred to the Service of Oncology where they initiated chemotherapy with Cysplatin (CDDP) and died 20 days later. The malignant mesothelioma peritoneal is a unfrequent entity, with limited therapeutic options; generally detected late, with a palliative treatment. PMID:20445731

Torrejón Reyes, Paul N; Frisancho, Oscar; Gómez, Aldo; Yábar, Alejandro



Malignancy and chronic renal failure.  


Increased incidence of cancer at various sites is observed in patients with end-stage renal disease (ESRD). Certain malignant diseases, such as lymphomas and carcinomas of the kidney, prostate, liver and uterus, show an enhanced prevalence compared with the general population. In particular, renal cell carcinoma (RCC) shows an excess incidence in ESRD patients. A multitude of factors, directly or indirectly associated with the renal disease and the treatment regimens, may contribute to the increased tumor formation in these patients. Patients undergoing renal replacement therapy (RRT) are prone to develop acquired cystic kidney disease (ACKD), which may subsequently lead to the development of RCC. In pre-dialysis patients with coexistent renal disease, as in dialysis and transplant patients, the presence of ACKD may predispose to RCC. Previous use of cytotoxic drugs (eg, cyclophosphamide) or a history of analgesic abuse, are additional risk factors for malignancy. Malignancy following renal transplantation is an important medical problem during the follow-up. The most common malignancies are lymphoproliferative disorders (early after transplantation) and skin carcinomas (late after transplantation). Another important confounder for risk of malignancy after renal transplantation is the type of immunosuppression. The type of malignancy is different in various countries and dependent on genetic and environmental factors. Finally, previous cancer treatment in a uremic patient on the transplant waiting list is of great importance in relation to waiting time and post-malignancy screening. PMID:17657083

Peces, Ramon



Occupational exposure and malignant lymphoma.  


The incidence of malignant lymphoma, especially non-Hodgkin's lymphoma has increased over the last few decades. This statement is true despite the fact that methods for diagnosing malignant lymphoma have changed and misclassification has become a problem. The present review is mainly concerned with occupational aspects of malignant lymphoma. Several subsequent studies have dealt with malignant lymphoma among woodworkers and pulp and paper mill workers pointing to increased risks. Exposure to phenoxy herbicides have provided reasonable evidence to be connected with an increased risk of non-Hodgkin's lymphoma, whereas there is limited information regarding Hodgkin's disease. The relationship between solvent exposure and malignant lymphoma has been observed in a great number of studies. It is, however, still hard to identify specific solvent compounds responsible for the increased risk. Other occupational exposures i.e. wood preservatives, welding, asbestos, hair dyes and exposure to animal viruses among meatworkers and veterinarians have also been studied in relation to malignant lymphoma. This review shows that occupational factors, especially exposure to solvents and phenoxy herbicides and also to wood, play a role in the epidemiology of malignant lymphoma. PMID:9117190

Persson, B



Dysmorphic face in two siblings with infantile neuroaxonal dystrophy.  


Infantile neuroaxonal dystrophy (INAD) is an autosomal recessive, neurodegenerative disease with onset in the first or second year of life. It has been reported that INAD shows numerous phenotype characteristics including problems associated with vision, hearing and physical coordination. It has however been very rare to see facial dysmorphism in these children. The study analyzes a girl and boy of a first cousin marriage with infantile neuroaxonal dystrophy affected at birth. At infancy, the children were examined in the Cerrahpa?a Medical Faculty Genetic Research Center, Istanbul. They had typical INAD features such as the lack of head control, vision, speech, sitting, and walking which are also seen in children with other congenital abnormalities. These children showed remarkable dysmorphism in the face which included prominent forehead, strabismus, small nose, fish mouth (boy), micrognathia, and large and low-settled ears. The presence of these facial features makes the patients appear unique and diagnosis more accurate. While these features are commonly seen diagnosis may be difficult at its onset. Until now this appearence has not been reported in INAD patients. In conclusion, in the first few months of life without any clinical or neurological signs, the physician should also consider diagnosing the disease of the infant as INAD. PMID:12558119

Seven, M; Ozkiliç, A; Yüksel, A



Propranolol for Infantile Haemangiomas: Experience from a Tertiary Center  

PubMed Central

Aim: Infantile haemangiomas are the most common tumor of infancy. We report the use of propranolol for treatment of problematic and complicated haemangiomas. Patients and Methods: Propranolol was given to 52 children with mean age of 18.2 months at onset of treatment. After clinical and electrocardiographic evaluations, propranolol was administered with a starting dose of 2 mg/kg per day, given in 3 divided doses. Monthly follow up was done, response to oral propranolol therapy and any complications of therapy were recorded. Response to propranolol was classified as Complete Response, Excellent Response, Partial Response and Non Responder. Results: Total 49 patients showed significant improvement after propranolol therapy out of which 4 patients were complete responder, 30 patients (56.7%) were excellent responders; 15 patients (28.8%) were partial responders. 3 patients (5.7%) had growth of haemangiomas despite propranolol therapy and were classified as non-responder. Side effect like hypotension, rashes, gastroesophageal reflux was reported by 3 patients. In our study mean duration of treatment was 6.5 months. At the end of treatment propranolol was stopped by with gradual tapering of dose over a period of 2 weeks. Conclusion: Propranolol administered orally at 2 mg/kg per day has rapid effective therapeutic effect in treatment of ulcerated haemangiomas and it appears to be a valuable and effective treatment option for infantile haemangiomas beyond the proliferative phase, and esthetically disfiguring haemangiomas.

Pandey, Vaibhav; Tiwari, Preeti; Gangopadhyay, Ajay N; Gupta, Dinesh K; Sharma, Shiv P; Kumar, Vijayendar



GABA(A) receptor properties in catastrophic infantile epilepsy.  


Catastrophic epilepsy due to cortical dysplasia is often intractable to anticonvulsant treatment. Many of the medications used unsuccessfully in treating this disorder are thought to exert at least a portion of their action through enhancement of inhibitory GABA(A) neurotransmission. In the present study, GABA(A) receptor properties in resected brain tissue from four infants with infantile spasms and intractable epilepsy due to cortical dysplasia were measured to determine if this clinical resistance to pharmacologic treatment correlates with alterations in receptor function. Results from epileptic cortex were compared with those from autopsy control samples. To perform these studies, we utilized the technique of injection of brain cellular membrane preparations into the Xenopus oocyte, which results in the incorporation of human GABA(A) receptors in their native configuration into the oocyte plasma membrane. Two-electrode voltage-clamp electrophysiology analysis was then performed to assess GABA(A) receptor pharmacologic properties. The intrinsic properties of affinity, reversal potential, current decay, and current rundown were unchanged in the epileptic infants. Current enhancement by benzodiazepines was also unaltered, as was the response to barbiturates. However, a significant decrease was found in the degree of GABA(A) current enhancement by neurosteroids in the epileptic infants, along with an increase in current inhibition by zinc. These findings may contribute to the mechanisms of intractability in catastrophic infantile epilepsy due to cortical dysplasia, and suggest alternative therapeutic approaches. PMID:18650066

Jansen, Laura A; Peugh, Lindsey D; Ojemann, Jeffrey G



[A case of congenital myotonic dystrophy with infantile autism].  


An 11-year-old girl with congenital myotonic dystrophy and infantile autism was reported. Her mother also suffered from typical myotonic dystrophy. Since her birth, the patient had been floppy, and showed bilateral talipes equinus at 1 year of age. Her subsequent psychomotor and speech development has been retarded. She showed autistic behavior and persistence to the sameness before 2 years old. She was admitted to Sawarabien at the age of 10 years. She could not talk anything but could understand simple, oral messages. Although she had severe degree of mental retardation, her ability for matching figures was relatively well reserved. Her autism was so manifest that it could not be explained by the degree of mental retardation. Neurological examinations revealed that she had facial diplegia, inverted V-shaped mouth, high-arched palate, talipes equinus, percussion myotonia of the tongue, generalized muscular atrophy and weakness, lordosis, areflexia, and congenital cataracta. The serum CPK was slightly elevated. EMG showed a myopathic pattern but did not show any myotonic discharge yet. The brachioradial muscle was biopsied and examined by light- and electron-microscopy. It mainly showed mild varieties of muscle fiber diameter and internal nuclei. Ultrastructurally, irregularly indented central nuclei and perinuclear degeneration of myofibrils associated with secondary lysosomes, lipid droplets and glycogen granules were revealed. Ventricular dilatation and some dysfunction of the brain were also revealed by CT scan and EEG respectively. The present case suggests that congenital myotonic dystrophy can be added into the disease group associated with infantile autism. PMID:2789860

Yoshimura, I; Sasaki, A; Akimoto, H; Yoshimura, N



A malignant itch.  

PubMed Central

We report an unusual presentation of a previously healthy three-year-old Chinese girl with a four-week history of apparently unexplained generalized intense itch. She had no past history of atopy or xerosis. Despite the severe itch, she had only minimal scratch marks on her right gluteal region but no flexural involvement. The girl was treated as having scabies and eczema and with oral antihistamines by various dermatologists without much improvement. She subsequently presented to a regional hospital with right hip pain and fever. Radiological and histopathological investigations confirmed that she had a peripheral T-cell lymphoma. The itch pattern prior to and following chemotherapy, as documented by the DigiTrac wrist-held movement monitor, showed a dramatic reduction of her nocturnal itch. The pattern was also very different from that of atopic dermatitis in that the scratching was of much higher intensity but lower frequency. Intractable pruritus associated with a peripheral T-cell lymphoma has not been previously reported in the pediatric literature. This report serves to alert clinicians of the gold paradigm that in a patient with an unexplained generalized itch, lymphoma and other malignancies must be considered. Images Figure 1 Figure 2 Figure 3

Hon, Kam-lun Ellis; Lam, Man-chin Adrian; Leung, Ting-fan; Chik, Ki-wai; Leung, Alexander K. C.



Galectins in hematological malignancies  

PubMed Central

Carbohydrates are traditionally considered to be an important source of energy for living organisms. In the field of biology, they are defined as organic compounds composed of carbon, hydrogen, and oxygen that are organized into ring structures. The analysis of these structures and their functions has led to a new field of biology called “glycobiology.” In the biomedical sciences, glycobiology is rapidly emerging to be an integral part of complex biological processes. Changes in glycan structures and the interactions of these structures with endogenous carbohydrate-binding proteins, known as lectins, are now considered to be potential biomarkers on cancer cells for monitoring tumor progression. Evidence suggesting that the interactions between lectins and their ligands have a major role in the different steps of cancer progression has accumulated at a rapid pace and has gained the attention of several oncologists. This is particularly true for galectin family members because changes in their expression levels correlate with alterations in cancer cell growth, apoptosis, and cell-cell and cell-matrix interactions. Here we provide an integrated view of the role of galectins in hematological malignancies.

St-Pierre, Yves



Catumaxomab: in malignant ascites.  


Catumaxomab is a rat/murine hybrid, trifunctional, bispecific (anti-human epithelial cell adhesion molecule [EpCAM]?×?anti-CD3) monoclonal antibody. Compared with paracentesis alone, paracentesis followed by catumaxomab therapy was associated with significant prolongation of paracentesis-free survival and time to repeat paracentesis in a randomized, open-label, multicentre, pivotal phase II/III trial in patients with recurrent symptomatic malignant ascites due to EpCAM-positive tumours who were resistant to conventional chemotherapy. The benefits of catumaxomab were seen across a broad range of epithelial ovarian and nonovarian cancers, and irrespective of whether or not catumaxomab recipients developed human anti-mouse antibodies. Combining catumaxomab with paracentesis also resulted in more pronounced and prolonged reductions in ascites signs and symptoms and a delayed deterioration in health-related quality of life compared with paracentesis alone. Despite the study not being designed or powered to evaluate overall survival, significant differences favouring the addition of catumaxomab to paracentesis were seen in analyses of the safety population and the subpopulation of patients with gastric cancer. Catumaxomab was generally well tolerated in the pivotal phase II/III trial. The most frequent adverse events attributed to catumaxomab treatment included cytokine-release-related symptoms, which were mostly of mild to moderate severity and manageable with standard symptomatic treatment. PMID:22676343

Frampton, James E



Occupational risk for hematological malignancies.  


A case-control study was conducted in 620 cases of hematological malignancies and in 1,240 age- and sex-matched controls in order to verify the possible association between occupation, toxic substances exposure, and the risk of hematological neoplasias. The results demonstrate that farmers and industrial workers have a significant risk for hematological malignancies. Exposure to asbestos, aromatic hydrocarbons, fertilizers, mineral oils, pesticides, and radiations is associated with a significant increase in the risk for these malignant diseases. These data are in agreement with previously reported data, and require a confirmation in larger, prospective studies. PMID:1951308

Pasqualetti, P; Casale, R; Colantonio, D; Collacciani, A



Infantile holocord cellular ependymoma with communicating hydrocephalus: unusual presentation of a rare case.  


We present a case of infantile holocord ependymoma in a 4-month-old boy who presented with infection of ventriculoperitoneal shunt done elsewhere for a communicating hydrocephalus. On magnetic resonance imaging, a diffuse holocord T2-hyperintense, T1-hypointense intramedullary bulky lesion with syringomyelia in the cervical level was seen. To the best of our knowledge, this is the first case of infantile holocord ependymoma. As the extent of morbidity associated with a spinal cord tumor is high, an increased level of suspicion and the need for a complete spinal cord screening in a case of infantile hydrocephalus without obvious clinical and radiological evidence of intracranial abnormality is emphasized. PMID:23512254

Aryan, Saritha; Ghosal, Nandita; Aziz, Zarina A; Hegde, A S; Dadlani, Ravi



Bile duct malignancies.  


Bile duct malignancies include intrahepatic cholangiocarcinoma (ICC), extrahepatic cholangiocarcinoma (ECC), gall bladder carcinoma (GC) and carcinoma of Vater's ampulla (ampulloma). Bile duct neoplasms are rare tumours with overall poor prognosis. The overall incidence affects up to 12.5 per 100,000 persons in the Czech Republic. The mortality rate has risen recently to 9.5 per 100,000 persons. The incidence and mortality have been remarkably stable over the past 3 decades. The survival rate of patients with these tumours is poor, usually not exceeding 12 months. The diagnostic process is complex, uneasy and usually late. Most cases are diagnosed when unresectable, and palliative treatment is the main approach of medical care for these tumours. The treatment remains very challenging. New approaches have not brought much improvement in this field. Standards of palliative care are lacking and quality of life assessments are surprisingly not common. From the scarce data it seems, however, that multimodal individually tailored treatment can prolong patients'survival and improve the health-related quality of life. The care in specialized centres offers methods of surgery, interventional radiology, clinical oncology and high quality supportive care. These methods are discussed in the article in greater detail. Improvements in this field can be sought in new diagnostic methods and new procedures in surgery and interventional radiology. Understanding the tumour biology on the molecular level could shift the strategy to a more successful one, resulting in more cured patients. Further improvements in palliative care can be sought by defining new targets and new drug development. The lack of patients with bile duct neoplasms has been the limiting factor for any improvements. A new design of larger randomized international multicentric clinical trials with prompt data sharing could help to overcome this major problem. Defining standards of palliative care is a necessity. Addressing health-related quality of life could help to assess the real benefit of palliative treatment. PMID:20806821

Tucek, S; Tomasek, J; Halámkova, J; Kiss, I; Andrasina, T; Hemmelová, B; Adámková-Krákorová, D; Vyzula, R



Genetics Home Reference: Malignant hyperthermia  


... plays an essential role in activating the RYR1 channel to release calcium ions into muscle cells. Although this gene is thought ... malignant hyperthermia? acidosis ; autosomal ; autosomal dominant ; calcium ; cell ; ... pharmacogenetics ; pharmacogenomics ; protein ; rhabdomyolysis ; surgery ; surgical ; ...


[Management of malignant pleural effusion].  


Malignant pleural effusions are the major cause of pleural effusions in patients older than 40. Their treatment is essentially palliative but recently improved with new efficient chemotherapy. The most frequent causes of malignant pleural effusions are pleural metastatic adenocarcinomas arising from lung in both sex, or from breast in women, and malignant mesothelioma. In both cases, thoracoscopy is useful for histological biopsies and sclerotherapy by talc poudrage. Pleural malignant mesotheliomas are linked in 70% of cases to professional asbestosis exposure. The histological diagnosis is difficult, relying on a standardized immunohistochemical analysis. Prophylactic irradiation has been proved to be efficient in the prevention of parietal seeding along the thoracocentesis and drainage channels. PET imaging could be of major interest in the diagnosis of mesothelioma and prognosis evaluation. Mesothelioma prognosis has recently been modified by the association of cisplatin with pemetrexed, a new antimetabolite agent, but mesothelioma remains seldom curable. PMID:17583136

Zalcman, Gérard; Lechapt, Emmanuèle; Bergot, Emmanuel



Ibrutinib for B cell malignancies  

PubMed Central

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.



Ibrutinib for B cell malignancies.  


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

Novero, Aileen; Ravella, Pavan M; Chen, Yamei; Dous, George; Liu, Delong



Drugs Approved for Malignant Mesothelioma

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.


AMG 319 Lymphoid Malignancy FIH

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



Malignant Mesothelioma: Treatment Option Overview  


... another part of the body, it is called metastasis . Cancer cells break away from where they began ( ... For example, if malignant mesothelioma spreads to the brain, the cancer cells in the brain are actually ...


Second Malignancies following Pure Seminoma  

Microsoft Academic Search

Purpose: Second malignancies in patients with pure testicular seminoma were studied in order to look for adverse late effects of treatment and to study the significance of second malignancies during follow-up. Patients, Methods: In a multicentric investigation, 839 consecutive patients with pure testicular seminoma were observed for a median follow-up of 3.9 years. Thirty-seven patients had been excluded from the

U. Rüther; K.-P. Dieckmann; R. Bussar-Maatz; F. Eisenberger



Malignant lymphoma involving the patella  

Microsoft Academic Search

The majority of skeletal lesions affecting the patella are benign and include entities such as chondroblastoma, giant cell\\u000a tumor, osteomyelitis, and gout. Malignant processes involving the patella are distinctly unusual. Isolated occurrences of\\u000a plasmacytoma, osteosarcoma, hemangiosarcoma, and metastatic disease have been reported. Malignant lymphoma involving the patella\\u000a is extremely uncommon, although lymphomatous infiltration of the skeletal system is not a

S. Cha; Elizabeth Schultz; Barbara McHeffey-Atkinson; David Sherr



Malignant glioma: Neuropathology and Neurobiology  

Microsoft Academic Search

\\u000a Zusammenfassung  Maligne Gliome können in jedem Lebensalter auftreten. Am häufigsten jedoch bei Erwachsenen, die das 40. Lebensjahr bereits\\u000a überschritten haben. Männer sind häufiger betroffen als Frauen. Maligne Gliome beinhalten ein Spektrum von Tumoren mit verschiedenen\\u000a Subtypen. Im Wesentlichen handelt es sich um Glioblastome, anaplastische Astrozytome \\/ Oligoastrozytome \\/ Oligodendrogliome,\\u000a die gemeinsam durch ein diffus infiltrierendes, rasches Wachstum und durch eine fatale

Matthias Preusser; Christine Haberler; Johannes A. Hainfellner



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

PubMed Central

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.

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



X-Ray Examinations for Prediction of the So-Called Infantile Scoliosis.  

National Technical Information Service (NTIS)

The present work contains a comparison of findings on 50 patients with progressive and resolving infantile scoliosis, as far as they are important for prognostication, with the investigations of Metha and other authors. These were the data obtained: 1. Am...

J. Schmelzer



Malignant transformation of oral lichen planus  

Microsoft Academic Search

Aims: To investigate the malignant potential of oral lichen planus (OLP), a common mucocutaneous disease of unknown aetiology. The malignant potential of OLP is still controversial, with studies reporting malignant transformation rates of between 0 and 5.6%. We also aimed to identify factors that might be associated with malignant transformation. Methods: We retrospectively reviewed the records of 832 patients with

R. Rajentheran; N. R. McLean; C. G. Kelly; M. F. Reed; A. Nolan



Desmoplastic infantile ganglioglioma/astrocytoma with cerebrospinal metastasis.  


Desmoplastic infantile ganglioglioma and astrocytoma (DIG/DIA) are rare intracranial tumours of early childhood that involve superficial cerebral cortex and leptomeninges. Despite the large size of the tumour and the presence of poorly differentiated cells, it is believed that the prognosis of DIG/DIA is excellent. We report two patients with DIG/DIA who developed multiple cerebrospinal metastases. To our knowledge only two similar cases have been reported in the literature. It appears that not all tumours with histological features of DIG/DIA behave in a benign way. It is possible that what is called DIG/DIA may be a heterogenous group of tumours with variable biological behaviour. PMID:17386372

Darwish, B; Arbuckle, Susan; Kellie, S; Besser, M; Chaseling, R



Molecular basis of infantile reversible cytochrome c oxidase deficiency myopathy  

PubMed Central

Childhood-onset mitochondrial encephalomyopathies are usually severe, relentlessly progressive conditions that have a fatal outcome. However, a puzzling infantile disorder, long known as ‘benign cytochrome c oxidase deficiency myopathy’ is an exception because it shows spontaneous recovery if infants survive the first months of life. Current investigations cannot distinguish those with a good prognosis from those with terminal disease, making it very difficult to decide when to continue intensive supportive care. Here we define the principal molecular basis of the disorder by identifying a maternally inherited, homoplasmic m.14674T>C mt-tRNAGlu mutation in 17 patients from 12 families. Our results provide functional evidence for the pathogenicity of the mutation and show that tissue-specific mechanisms downstream of tRNAGlu may explain the spontaneous recovery. This study provides the rationale for a simple genetic test to identify infants with mitochondrial myopathy and good prognosis.

Kemp, John P.; Tuppen, Helen A. L.; Hudson, Gavin; Oldfors, Anders; Marie, Suely K. N.; Moslemi, Ali-Reza; Servidei, Serenella; Holme, Elisabeth; Shanske, Sara; Kollberg, Gittan; Jayakar, Parul; Pyle, Angela; Marks, Harold M.; Holinski-Feder, Elke; Scavina, Mena; Walter, Maggie C.; Coku, Jorida; Gunther-Scholz, Andrea; Smith, Paul M.; McFarland, Robert; Chrzanowska-Lightowlers, Zofia M. A.; Lightowlers, Robert N.; Hirano, Michio; Lochmuller, Hanns; Taylor, Robert W.; Chinnery, Patrick F.; Tulinius, Mar; DiMauro, Salvatore



Molecular basis of infantile reversible cytochrome c oxidase deficiency myopathy.  


Childhood-onset mitochondrial encephalomyopathies are usually severe, relentlessly progressive conditions that have a fatal outcome. However, a puzzling infantile disorder, long known as 'benign cytochrome c oxidase deficiency myopathy' is an exception because it shows spontaneous recovery if infants survive the first months of life. Current investigations cannot distinguish those with a good prognosis from those with terminal disease, making it very difficult to decide when to continue intensive supportive care. Here we define the principal molecular basis of the disorder by identifying a maternally inherited, homoplasmic m.14674T>C mt-tRNA(Glu) mutation in 17 patients from 12 families. Our results provide functional evidence for the pathogenicity of the mutation and show that tissue-specific mechanisms downstream of tRNA(Glu) may explain the spontaneous recovery. This study provides the rationale for a simple genetic test to identify infants with mitochondrial myopathy and good prognosis. PMID:19720722

Horvath, Rita; Kemp, John P; Tuppen, Helen A L; Hudson, Gavin; Oldfors, Anders; Marie, Suely K N; Moslemi, Ali-Reza; Servidei, Serenella; Holme, Elisabeth; Shanske, Sara; Kollberg, Gittan; Jayakar, Parul; Pyle, Angela; Marks, Harold M; Holinski-Feder, Elke; Scavina, Mena; Walter, Maggie C; Coku, Jorida; Günther-Scholz, Andrea; Smith, Paul M; McFarland, Robert; Chrzanowska-Lightowlers, Zofia M A; Lightowlers, Robert N; Hirano, Michio; Lochmüller, Hanns; Taylor, Robert W; Chinnery, Patrick F; Tulinius, Mar; DiMauro, Salvatore



Frontotemporal abnormal gyration with infantile spasms in identical twins.  


We describe the case of 10-year-old twin girls, who were born to nonconsanguineous parents and showed pes equinovarus, infantile spasms, and severe psychomotor retardation. Neither patient showed marked microcephaly. Neuroimaging revealed a simplified gyral pattern in the bilateral frontotemporal areas, a reduced volume of cerebral white matter, and a thin corpus callosum in both patients. The cerebral cortex presented with significant thickness in the anterior temporal region at the age of 10 years, which suggest that the simplified gyri can evolve into the pachygyria during postnatal period. These cases may represent a hereditary brain malformation with a distinct pattern of abnormal cortical gyration. The age-dependent change in appearance of dysgenetic cortex should be further explored in cases with brain malformations. PMID:17416476

Saito, Yoshiaki; Yokoyama, Atsushi; Shiraishi, Hideyuki; Maegaki, Yoshihiro; Ohno, Kousaku



Infantile Dural Arteriovenous Shunt Draining into a Developmental Venous Anomaly  

PubMed Central

Summary A three-year-old girl with an incidentally discovered infantile type of dural arteriovenous shunts (DAVs) along the superior sagittal sinus during investigation of a minor head trauma is presented. The DAVs drained into a developmental venous anomaly of the right cerebral hemisphere. In addition, there was a small cavernoma within the territory drained by the DVA. The patient underwent multiple transarterial embolizations to decrease the shunt flow and thus the constrained venous drainage of the DVA and right cerebral hemisphere. Pediatric dural arteriovenous shunts are a different entity from the adult type DAVs and should be managed according to the growth and development of the child. DVAs are extreme variations of the venous system with reduced flexibility to increased venous drainage. Regardless of the type of treatment employed, the DVA and its drainage pathway must be preserved.

Geibprasert, S.; Krings, T.; Pereira, V.; Lasjaunias, P.



Mineral balance in infantile cortical hyperostosis: effects of corticosteroids.  

PubMed Central

The effects on mineral metabolism of therapeutic doses of corticosteroids were investigated in infantile cortical hyperostosis; in four untreated cases the calcium, phosphorus, and magnesium balances were strongly positive. In one severe case, treatment with prednisolone was associated with an alteration to negative calcium and magnesium balance, and faecal losses of calcium were particularly high. This effect persisted for at least three months after the steroids had been discontinued, and during this period there was pronounced retardation of linear growth. Six months after the treatment had been stopped mineral balance was again positive and there was rapid 'catch up' in growth. In infancy, the negative effect of corticosteroids on calcium, phosphorus, and magnesium metabolism may contribute to inhibition of bone growth and steroid stunting.

Barr, D G; Belton, N R



Gastric volvulus manifesting as infantile wheezing: a puzzling presentation.  


Gastric volvulus is a rare disease in the pediatric population. Its clinical presentation is exceedingly variable, and without a high index of suspicion, delayed or missed diagnosis is not uncommon as illustrated by this report of a 13-month-old boy with a puzzling presentation of chronic wheezing and cough for 1 year. There were no gastrointestinal symptoms. The symptoms were attributed to bronchiolitis, pneumonia, laryngomalacia, or reactive airway disease by several practicing physicians. A detailed history revealed that the wheezing got worse after large meals. This information prompted an upper gastrointestinal contrast study, which led to the identification of organoaxial gastric volvulus and coexisting gastroesophageal reflux. The respiratory symptoms resolved dramatically after antireflux medications and lifestyle modification for gastroesophageal reflux. This report highlights chronic gastric volvulus in the differential diagnosis of infantile wheezing, particularly when the wheezing is present very early in life and associated with feeding. PMID:21822083

Su, Chia-Yi; Chang, Wei-Hsuan; Huang, Jing-Long; Yao, Tsung-Chieh



Infantile colic--less common than previously estimated?  


A two-part population-based study investigating the occurrence of infantile colic was undertaken, in which 92% of mothers with newborn healthy infants were reached. In the prospective part 152 mothers ("diary group") registered crying and fussing in their infants during 12 weeks. In the retrospective part 224 mothers ("interview group") were contacted by telephone at an infant age of 5-7 months. The colic occurrence was determined according to four different definitions; the rate varied from 3.3 to 17.1%. The classical "Wessel-type" colic was present in 9.3%. Colic defined as "crying seen as a problem by parent" was present in 12.1% of the "interview group", but in only 3.3% of the "diary group". Some earlier studies may have overestimated colic occurrence. Another possibility is an actual decline. The contributive part of preventive measures is discussed. PMID:8740304

Canivet, C; Hagander, B; Jakobsson, I; Lanke, J



PRRT2 mutation causes benign familial infantile convulsions.  


Benign familial infantile convulsions (BFIC) is an autosomal dominantly inherited epilepsy syndrome with onset between 3 and 12 months of age. It is characterized by brief seizures with motor arrest, cyanosis, hypertonia, and limb jerks. Seizures respond well to antiepileptic drugs and remission occurs before the age of 3 years.(1) Several recent publications described heterozygous mutations in the proline-rich transmembrane protein 2 (PRRT2) gene on chromosome 16p11.2, one of the known BFIC loci,(2,3) in an increasingly large number of families with paroxysmal kinesigenic dyskinesia (PKD) and PKD with infantile convulsions (PKD/IC).(4-6) The majority of PRRT2 mutations result in a premature truncation of PRRT2 protein. Although its exact function is unknown, recent studies indicated that PRRT2 is highly expressed in the developing nervous system and localized in axons in primary neuronal cultures.(6) Through binding to synaptic protein SNAP25, PRRT2 may be involved in vesicle docking and calcium-triggered neuronal exocytosis.(6) Preliminary functional studies of truncated PRRT2 mutants showed either a loss of membrane localization in COS-7 cells(5) or near absence of mutant protein in hippocampal neuronal cultures(6) that is likely due to nonsense mediated RNA decay. One can speculate that mutant PRRT2 protein may result in abnormal neurotransmitter release and neuronal hyperexcitability that could explain the clinical symptoms seen with PKD and PKD/IC. We tested whether PRRT2 is also the causal gene in families with BFIC without associated paroxysmal dyskinesia. PMID:23077019

de Vries, Boukje; Callenbach, Petra M C; Kamphorst, Jessica T; Weller, Claudia M; Koelewijn, Stephany C; ten Houten, Robert; de Coo, Irenaeus F M; Brouwer, Oebo F; van den Maagdenberg, Arn M J M



A Case of "Late-Onset" Idiopathic Infantile Hypercalcemia Secondary to Mutations in the CYP24A1 Gene.  


Objective: Mutations in the 24-hydroxylase gene, CYP24A1, have recently been reported to cause idiopathic infantile hypercalcemia (IIH), a rare disease presenting in the first year of life that is characterized by increased sensitivity to vitamin D, leading to severe symptomatic hypercalcemia.Methods: We present a case report and review the relevant literature.Results: A 24-year-old Caucasian man presented with repetitive signs of nephrolithiasis since the age of 18 years, hypercalciuria (17.1 mmol/24 h), slightly elevated serum calcium concentration (2.64 mmol/L), and inappropriately high levels of 1,25-dihydroxyvitamin D (101 pg/mL) in combination with suppressed levels of circulating parathormone (7.9 pg/mL). Exogenous vitamin D intoxication as well as granulomatous disease or malignancy were excluded. Genetic analysis revealed a loss-of-function mutation in CYP24A1. Of note, our patient denied any prior clinical signs of impaired calcium homeostasis during childhood.Conclusion: Here, we describe the exceptional case of a patient with hypercalciuria and recurrent nephrolithiasis secondary to mutations in CYP24A1, without any signs of IIH in childhood, indicating that the phenotypic spectrum includes mild "late-onset" disease that becomes symptomatic in adolescence. Therefore, reduced CYP24A1 activity should be considered as a possible reason for recurrent nephrolithiasis in adults. PMID:24518185

Wolf, Peter; Müller-Sacherer, Thomas; Baumgartner-Parzer, Sabina; Winhofer, Yvonne; Kroo, Judit; Gessl, Alois; Luger, Anton; Krebs, Michael



Effectiveness of Mentha piperita in the Treatment of Infantile Colic: A Crossover Study  

PubMed Central

Background. Infantile colic is a distressing and common condition for which there is no proven standard treatment. Objective. To compare the efficacy of Mentha piperita with simethicone in treatment for infantile colic. Methods. A double-blind crossover study was performed with 30 infants attending IMIP, Recife, Brazil. They were randomized to use Mentha piperita or simethicone in the treatment of infantile colic during 7 days with each drug. Primary outcomes were mother_s opinion about responses to the treatment, number of daily episodes of colic, and time spent crying, measured by a chronometer. Mann-Whitney and chi-square tests were used to compare the results. This study was previously approved by the Ethical Committee in Research at IMIP. Results. At baseline daily episodes of infantile colic was 3.9 (±1.1) and the mean crying time per day was 192 minutes (±51.6). At the end of the study daily episodes of colic fell to 1.6 (±0.6) and the crying duration decreased to 111 (±28) minutes. All mothers reported decrease of frequency and duration of the episodes of infantile colic and there were no differences between responses to Mentha piperita and simethicone. Conclusions. These findings suggest that Mentha piperita may be used to help control infantile colic. However, these results must be repeated by others studies.

Alves, Joao Guilherme Bezerra; de Brito, Rita de Cassia Coelho Moraes; Cavalcanti, Telma Samila



[Thoracoscopy in malignant pleural effusions].  


To assess the value of thoracoscopy in malignant pleural effusions, the procedure and results of thoracoscopy by using a fiberoptic bronchoscope and a rigid cold-light thoracoscope in 130 cases with malignant pleural effusion are reported. The overall diagnostic rate was 91.5% (119/130). The malignant pleural mesothelioma in 24 cases and metastatic cancers in 95 cases were histopathologically confirmed. Talcum powder, tetracycline and Corynebacterium parvum were separately sprayed through thoracoscope into pleural cavity in 69, 10 and 10 patients, and the success rates of complete and lasting pleurodesis were 87.0%, 5/10 and 8/10 respectively. Postoperative complications included transient fever and chest pain, local subcutaneous emphysema in 6 cases and tumor seeding at thoracoscopy site in 4 cases. It is concluded that thoracoscopy is simple, safe, reliable and of high practical value in the diagnosis of malignant pleural effusions and in assessment before exploratory thoracotomy, and that transendoscopical administration of drugs for pleurodesis is a very effective method for controlling malignant pleural effusions. The efficacy of the talc poudrage is better than tetracycline and Corynebacterium parvum. PMID:9206045

Zhang, D; Chen, Y; Tu, C



Phenotypes and PRRT2 mutations in Chinese families with benign familial infantile epilepsy and infantile convulsions with paroxysmal choreoathetosis  

PubMed Central

Background Mutations in the PRRT2 gene have been identified as the major cause of benign familial infantile epilepsy (BFIE), paroxysmal kinesigenic dyskinesia (PKD) and infantile convulsions with paroxysmal choreoathetosis/dyskinesias (ICCA). Here, we analyzed the phenotypes and PRRT2 mutations in Chinese families with BFIE and ICCA. Methods Clinical data were collected from 22 families with BFIE and eight families with ICCA. PRRT2 mutations were screened using PCR and direct sequencing. Results Ninety-five family members were clinically affected in the 22 BFIE families. During follow-up, two probands had one seizure induced by diarrhea at the age of two years. Thirty-one family members were affected in the eight ICCA families, including 11 individuals with benign infantile epilepsy, nine with PKD, and 11 with benign infantile epilepsy followed by PKD. Two individuals in one ICCA family had PKD or ICCA co-existing with migraine. One affected member in another ICCA family had experienced a fever-induced seizure at 7 years old. PRRT2 mutations were detected in 13 of the 22 BFIE families. The mutation c.649_650insC (p.R217PfsX8) was found in nine families. The mutations c.649delC (p.R217EfsX12) and c.904_905insG (p.D302GfsX39) were identified in three families and one family, respectively. PRRT2 mutations were identified in all eight ICCA families, including c.649_650insC (p.R217PfsX8), c.649delC (p.R217EfsX12), c.514_517delTCTG (p.S172RfsX3) and c.1023A?>?T (X341C). c.1023A?>?T is a novel mutation predicted to elongate the C-terminus of the protein by 28 residues. Conclusions Our data demonstrated that PRRT2 is the major causative gene of BFIE and ICCA in Chinese families. Site c.649 is a mutation hotspot: c.649_650insC is the most common mutation, and c.649delC is the second most common mutation in Chinese families with BFIE and ICCA. As far as we know, c.1023A?>?T is the first reported mutation in exon 4 of PRRT2. c.649delC was previously reported in PKD, ICCA and hemiplegic migraine families, but we further detected it in BFIE-only families. c.904_905insG was reported in an ICCA family, but we identified it in a BFIE family. c.514_517delTCTG was previously reported in a PKD family, but we identified it in an ICCA family. Migraine and febrile seizures plus could co-exist in ICCA families.



Gastrointestinal malignancy and the microbiome.  


Microbial species participate in the genesis of a substantial number of malignancies-in conservative estimates, at least 15% of all cancer cases are attributable to infectious agents. Little is known about the contribution of the gastrointestinal microbiome to the development of malignancies. Resident microbes can promote carcinogenesis by inducing inflammation, increasing cell proliferation, altering stem cell dynamics, and producing metabolites such as butyrate, which affect DNA integrity and immune regulation. Studies in human beings and rodent models of cancer have identified effector species and relationships among members of the microbial community in the stomach and colon that increase the risk for malignancy. Strategies to manipulate the microbiome, or the immune response to such bacteria, could be developed to prevent or treat certain gastrointestinal cancers. PMID:24406471

Abreu, Maria T; Peek, Richard M



[VATS in malignant pleural effusions].  


Between November 1992 and October 1996, 20 patients with malignant pleural effusions were submitted to VATS under general anesthesia. The overall positive histological diagnoses were obtained through VATS (20/20). The malignant pleural mesothelioma in 8 cases and metastatic cancers in 12 cases were histopathologically confirmed. Talc pleurodesis was performed for all the cases, and 18 patients gained lasting pleurodesis and the other 2 patients did not. The failure of pleurodesis was due to that the lung could not reexpand to come into contact with the chest wall. Postoperative complications included transient fever and slight asthma in 2 cases, and the symptoms were relieved obviously after some simple therapy to symptom. In conclusion, VATS has provided a high positive diagnosis of patients with malignant pleural effusions not diagnosed by conventional methods and good results in pleurodesis, but some operating skills must be emphasized. PMID:10678010

Cui, Y; Wang, J; Liu, T



Round Cell Vaginal Malignant Melanoma  

PubMed Central

Malignant melanoma is predominantly a skin disease but in rare instances it may occur at other sites. A vaginal melanoma is a rare clinical entity and the round cell type is an uncommon variant. Although the present case was clinically diagnosed as a urethral caruncle, on histopathological examination and immunostaining it was diagnosed as a round cell pigmented malignant melanoma. The patient refused radical surgery and was given a full course radiotherapy treatment but died a year later. Malignant vaginal melanoma carries a very poor prognosis even when lesion is localised at the time of presentation. The five-year survival rate ranges from 10–20% with the prognosis being influenced by tumour size. A tumour size ?3cm has a poor prognosis. Age, mitotic count, stage, and location of the lesion do not influence survival rates.

Chauhan, Neena; Gaur, Dushyant S.; Pathak, Ved P.



Cytology of canine malignant histiocytosis.  


Cytologic features of bone marrow, tissue, and abdominal fluid in seven cases of malignant histiocytosis in dogs are described, and histopathology, hematology, and serum biochemistry of the cases are reviewed. Diagnosis of malignant histiocytosis was confirmed by tissue morphology and immunohistochemistry; neoplastic cells in all cases had positive immunoreactivity to lysozyme. This stain can be used to definitively establish the diagnosis of malignant histiocytosis on cytology specimens as well as tissue sections. Cytologic findings included numerous pleomorphic, large, discrete mononuclear cells with abundant, lightly basophilic, vacuolated, granular cytoplasm. Nuclei were round to oval to reniform with marked anisocytosis and anisokaryosis; nucleoli were prominent. Mitotic figures, often bizarre, were occasionally seen. Multinucleated giant cells and phagocytosis of erythrocytes and leukocytes were prominent features in cytologic preparations in four cases. Four dogs were anemic, five dogs were thrombocytopenic, and three dogs were hypercalcemic. Breeds affected included Doberman Pinscher (1), Golden Retriever (2), Flat Coated Retriever (3), and mixed-breed dog (1). PMID:12666013

Brown, Diane E.; Thrall, Mary Anna; Getzy, David M.; Weiser, M. Glade; Ogilvie, Gregory K.



Endoscopic palliation of esophageal malignancy.  


Historically, the development and marketing of the neodymium-yttrium-aluminum-garnet (Nd:YAG) laser was associated with the insertion of markedly fewer conventional prostheses for the palliation of malignant dysphagia. Subsequently, the introduction of self-expandable metal stents (SEMS) has, in turn, led to a diminished role not only for laser therapy but also for other ablative modalities, including bipolar cautery, argon plasma coagulation (APC), and the injection of caustics. Two ablative modalities deserve ongoing consideration, but not because they have been proven to be better or more cost-effective than SEMS. These include photodynamic therapy (PDT), because of its potential to ablate large areas of low-grade malignancy, and injection of chemotherapeutic agents or T-lymphocytes sensitized to an individual malignancy. The latter, while theoretically promising, will require considerably more study before widespread clinical application. PMID:12929047

Kozarek, R A



Primary malignant melanoma of gallbladder.  


Gallbladder primary malignant melanoma (GPMM) is a rare and controversial entity. The existing controversy on the subject appears mainly because of the lack of definitive objective criteria of primitivity. Objective criteria proposed by the specific literature for distinguishing GPMM from secondary gallbladder melanoma include the exclusion of previous primitive melanoma, absence of synchronous involment of other sites, the unicity of lesion, its polipoid or papilary shape and the presence of a junctional melanocitary component. After laparoscopic cholecystectomy in one of our patients, dark polypus inside the gallbladder was found. A malignant melanoma was diagnosed according to all five criteria for GPMM. PMID:21263401

Pitlovi?, Vlatka; Lati?, Ferid; Pitlovi?, Hrvoje; Rupci?, Mario; Jurisi?, Darko; Lati?, Azra



Dyskeratosis congenita with malignant transformation.  


Dyskeratosis congenita (DC) is a rare genodermatosis characterised by a classic triad of dystrophic nails, reticular skin pigmentation and mucous membrane leukoplakic patches, which have a high rate of malignant transformation. The case report presented here deals with a sporadic case of DC without similar clinical presentation in the first-degree and second-degree relatives. Of note in this case, there was rapid malignant transformation in the non-homogeneous nodulo-speckled leukoplakic patch on the dorsum of the tongue. PMID:22715219

Ray, Jay Gopal; Swain, Niharika; Ghosh, Ranjan; Richa; Pattanayak Mohanty, Swetag



Second Malignant Neoplasms Following Radiotherapy  

PubMed Central

More than half of all cancer patients receive radiotherapy as a part of their treatment. With the increasing number of long-term cancer survivors, there is a growing concern about the risk of radiation induced second malignant neoplasm [SMN]. This risk appears to be highest for survivors of childhood cancers. The exact mechanism and dose-response relationship for radiation induced malignancy is not well understood, however, there have been growing efforts to develop strategies for the prevention and mitigation of radiation induced cancers. This review article focuses on the incidence, etiology, and risk factors for SMN in various organs after radiotherapy.

Kumar, Sanath



Benign infantile convulsion as a diagnostic clue of paroxysmal kinesigenic dyskinesia: a case series  

PubMed Central

Introduction Paroxysmal kinesigenic dyskinesia is characterized by sudden attacks of involuntary movements. It is often misdiagnosed clinically as psychogenic illness, which distresses the patients to a great extent. A correct diagnosis will improve the quality of life in patients with paroxysmal kinesigenic dyskinesia because treatment with low doses of anticonvulsants is effective for eliminating the clinical manifestations. Paroxysmal kinesigenic dyskinesia can occur independently of or concurrently with benign infantile convulsion. Identification of PRRT2 as the causative gene of benign infantile convulsion and paroxysmal kinesigenic dyskinesia allows genetic confirmation of the clinical diagnosis. Case presentation We describe the clinical features of a Japanese family with either paroxysmal kinesigenic dyskinesia or benign infantile convulsion. A PRRT2 missense mutation (c.981C?>?G, p.Ile327Met) was identified in two patients with benign infantile convulsion and three patients with paroxysmal kinesigenic dyskinesia as well as in two unaffected individuals. Allowing incomplete penetrance in the mutation carriers, this mutation co-segregated completely with the phenotype. The patients with paroxysmal kinesigenic dyskinesia had been misdiagnosed with psychogenic illness for many years. They were correctly diagnosed with paroxysmal kinesigenic dyskinesia when their children visited a pediatrician for benign infantile convulsion. Treatment with carbamazepine controlled their involuntary movements completely. Conclusions Paroxysmal kinesigenic dyskinesia is a treatable movement disorder that is often misdiagnosed clinically as psychogenic illness. It is important to note that two clinically distinct disorders, benign infantile convulsion and paroxysmal kinesigenic dyskinesia, are allelic conditions caused by PRRT2 mutations. Paroxysmal kinesigenic dyskinesia should be suspected in families with a child with benign infantile convulsion.



Epidemiological Study of Malignant Melanoma.  

National Technical Information Service (NTIS)

Between 1972 and April 15, 1979, 771 patients treated for primary malignant melanoma at New York University Medical Center were interviewed by the NYU Melanoma Cooperative Group. From the beginning of this study to January 31, 1982, an additional 364 case...

B. S. Pasternack



Thoracic Malignancy Steering Committee Roster

Thoracic Malignancy Steering Committee Roster Co-chairs A. William Blackstock, M.D.Wake Forest School of MedicineWinston-Salem, NC David H. Harpole Jr., M.D.Duke UniversityDurham, NC Members Mark A. Socinski, M.D. [Chair Emeritus]University of PittsburghPittsburgh,


Malignant rhabdoid tumor of liver  

PubMed Central

Malignant rhabdoid tumor (MRT) is a rare, but aggressive tumor commonly arising from the kidney in young children. Extrarenal MRT has been reported in the literature in various other sites including the liver, pelvis, CNS, abdomen, heart and other soft-tissues. Reported herein are the presentation, radiology, histopathology, immunohistochemistry, treatment and outcome of a 6 month infant with primary MRT of liver.

Agarwala, Sandeep; Jindal, Bibekanand; Jana, Manisha; Bhatnagar, Veereshwar; Gupta, Arun Kumar; Iyer, Venkateshwar K.



Brain Malignancies Steering Committee Roster

Brain Malignancies Steering Committee Roster Co-chairs Ian Pollack, M.D., F.A.C.S., F.A.A.PChildren's Hospital of PittsburghPittsburgh, PA W.K. Alfred Yung, M.D.University of Texas - M.D. Anderson Cancer CenterHouston, TX Members Karla Ballman, Ph.D.Mayo


Sunscreen use and malignant melanoma.  


In a new population-based, matched, case-control study from southern Sweden of 571 patients with a first diagnosis of cutaneous malignant melanoma, between 1995 and 1997, and 913 healthy controls aged 16 to 80 years, the association between sunscreen use and malignant melanoma was evaluated. The median sun protection factor (SPF) used by both cases and controls was 6, range 2 to 25. Sunscreen users reported greater sun exposure than non-users. Persons who used sunscreens did not have a decreased risk of malignant melanoma. Instead, a significantly elevated odds ratio (OR) for developing malignant melanoma after regular sunscreen use was found, adjusted for history of sunburns, hair color, frequency of sunbathing during the summer, and duration of each sunbathing occasion ¿OR = 1.8, 95% confidence interval (CI) 1.1-2.9]. The OR was higher in subjects who reported that sunscreen use enabled them to spend more time sunbathing (adjusted OR = 8.7, 95% CI 1.0-75.8 for always vs. never use). The association appeared to hold for subjects who did not suffer from sunburns while using sunscreens, for subjects who used SPF of 10 or lower, and among men. The pattern of a significantly increased melanoma risk was seen only for lesions of the trunk. Our results are probably related mainly to earlier sunscreens of low SPF. They substantiate the hypothesis that sunscreen use, by permitting more time sunbathing, is associated with melanoma occurrence. PMID:10861466

Westerdahl, J; Ingvar, C; Mâsbäck, A; Olsson, H



Malignant transformation of uterine leiomyoma  

PubMed Central

A rare case of malignant transformation of uterine leiomyoma is reported. A 54 year old lady, nulliparous and 2 years postmenopausal presented to gynecology clinic with a pelvi – abdominal mass and ultrasound scan suggestive of multiple uterine fibroid. Total abdominal hysterectomy performed. Histopathology report showed leiomyosarcomative changes from benign leiomyoma within the huge mass.

Al Ansari, Afaf A.; Al Hail, Fatima A.; Abboud, Emad



Malignant neoplastic disease in women.  


This study refers to a longitudinal population study of women in Gothenburg, Sweden. The prevalences of malignant neoplastic disease in two cross-sectional studies in 1968-1969 and in 1980-1981, respectively, and incidence figures for the 12-year period between these cross-sectional studies are presented. The data on malignant neoplasms were based on interview of the participants in the population study, on information from the Cancer Registry of the Swedish National Board of Health and Welfare and from the Swedish National Bureau of Statistics and were confirmed by death certificates, inpatient and outpatient records and reexaminations of tissue specimens from the tumor tissue. The prevalences of malignant neoplastic disease increased with age from 0.3% at the age of 38 to 9.9% in women aged 60. The incidence rates during the 12-year period increased with age from about 2% in women aged 38 at the beginning of the study to be about 10% in women initially aged 60. Breast cancer was found to be the most common single malignant neoplasm followed by cancer of uterus and cancer of the ovaries. PMID:2370921

Helgesson, O; Bengtsson, C; Lapidus, L; Merck, C



Epigenetic lesions in malignant melanoma.  


Malignant melanoma arises through a series of genetic and epigenetic events. A more profound understanding of the biology of metastatic melanoma should greatly aid in the development of new and effective treatments. Currently, avenues being pursued to improve treatment of metastatic melanoma include dendritic cell vaccines and other vaccination strategies, tyrosine kinase inhibitors, adoptive transfer of ex vivo stimulated T cells, and, as reviewed here, epigenetic approaches. The "methylator phenotype", with inactivation by promoter hypermethylation of numerous genes in malignant melanoma cell lines and primary tumors (p16, PTEN, RASSF1, estrogen receptor, retinoic acid receptor beta, SOCS1 and -2, MGMT etc.) offers a strong rationale for treatment approaches based on the use of DNA demethylating agents. The clinical literature on treatment of metastasized malignant melanoma with either 5-azacytidine or 5-aza-2'-deoxycytidine (decitabine) is reviewed. Future trials in malignant melanoma with these compounds might profit from prolonged low-dose exposure, since they unfold their full effects not immediately but with a certain delay, which may be associated with their DNA demethylating activity. Combinations of DNA demethylation agents with either histone deacetylase inhibitors, interleukin-2, chemotherapy or tamoxifen have been embarked on both in in vitro models of melanoma and recent clinical trials. The in vitro synergism between inhibitors of DNA methylation and histone deacetylation strongly invites a systematic study of combinations of both groups of agents. Up-regulation of cancer testis antigens by epigenetic therapy in melanoma also offers a very strong rationale to place these drugs and schedules within a larger treatment concept of immunotherapy which may include also T cell activation e.g. by interleukin-2, and vaccination strategies. In conclusion, the epigenome of malignant melanoma, with a well-established in vitro reversal potential, holds promise as a novel molecular target. PMID:18289047

Schwabe, M; Lübbert, M



Diagnosis and Treatment of Malignant Pleural Effusions.  

National Technical Information Service (NTIS)

Contents: Radiological diagnosis in evaluating malignant pleural effusions; Biopsy, cytology, cell culture and electron microscopy in the diagnosis of malignant pleural effusions; Biological and immunological markers of maligant pleural effusions; Drug th...



New optional photodynamic therapy laser wavelength for infantile port wine stains: 457 nm  

NASA Astrophysics Data System (ADS)

To expand the optional laser wavelengths of photodynamic therapy (PDT) for port wine stain (PWS), the feasibility of applying a 457 nm laser to the PDT for infantile PWS was analyzed by mathematical simulation and was validated by clinical experiment. Singlet oxygen yield of 457 nm PDT or 532 nm PDT in an infantile PWS model and an adult PWS model was theoretically simulated. Fifteen PWS patients (14 infants and 1 adult) with 40 spots were treated with 457 nm (20 spots) and 532 nm (20 spots), respectively, in two PDT courses. Simulation results showed that under the same power density and irradiation time, singlet oxygen yield of 457 nm PDT and 532 nm PDT are similar in infantile PWS vessels. Yet, in adult PWS vessels, singlet oxygen yield of 457 nm PDT is lower than 532 nm PDT. Clinical outcomes showed that no statistic difference existed between 457 nm PDT and 532 nm PDT for infantile PWS. The result of this study suggested that 457 nm wavelength laser has the potential to be applied in PDT for infantile PWS.

Wang, Ying; Zuo, Zhaohui; Gu, Ying; Huang, Naiyan; Chen, Rong; Li, Buhong; Qiu, Haixia; Zeng, Jing; Zhu, Jianguo; Liang, Jie



Infantile hypertrophic pyloric stenosis in Belfast, 1957-1969.  

PubMed Central

Infants with hypertrophic pyloric stenosis born in Belfast during the 13 years 1957-1969 have been reviewed. Their distribution shows a bias towards higher social classes, breast feeding, and primogeniture. Obstetric factors and parental ages seem to be of no importance. More affected infants were born during winter months than would be expected. The overall incidence of infantile pyloric stenosis in this community has fallen during the period under review. Clinically, the patients started vomiting at a mean age of 22 days and it is recommended that the condition should not be called 'congenital'. The size of the tumour is mainly determined by the size of the patient, rather than by his age or duration of symptoms. Attention is drawn to the occurrence of haematemesis in 17-5% and melaena in 2-9% of infants. Jaundice occurred in 1-8% of patients in this series, and is attributed to the adverse effect of starvation on hepatic glucuronyl transferase activity. Other conditions noted in these patients included inguinal hernia, partial thoracic stomach, and phenylketonuria. Subsequent growth and development were in the anticipated range.

Dodge, J A



Late rebound of infantile hemangioma after cessation of oral propranolol.  


Propranolol has become the first line of treatment for infantile hemangiomas (IHs), with a high response rate, but rebound growth after cessation of propranolol has been reported, primarily in the first year of life. We sought to determine the frequency and associated factors leading to late regrowth after successful treatment at an age when the proliferative phase has usually ceased. We retrospectively reviewed the clinical charts, serial photographs, and radiologic images of children with rebound IH occurring after the age of 15 months after a successful course of oral propranolol averaging 2.6 mg/kg/day (range 2-3 mg/kg/day). Thirteen (10 female, 3 male) of 212 patients (6%) treated with oral propranolol since 2008 were evaluated. The mean age at the start of treatment was 5.3 months (range 1.8-13 months), and an average of 10.3 months (range 4.5-16 months) of treatment was given. It took an average of 5.3 months (range 1-13.8 months) for a significant rebound to appear. Late rebound after successful propranolol indicates a prolonged proliferation phase of IH even after 15 months of age. This is compared with previous reports of rebound, which occurred primarily in infants younger than 1 year old. Late proliferation can occur in localized, small, mixed, and deep IH, even after several months of a positive response to propranolol. A second course of propranolol readily controlled the recurrence. PMID:24016283

Shehata, Nancy; Powell, Julie; Dubois, Josée; Hatami, Afshin; Rousseau, Elizabeth; Ondrejchak, Sandra; McCuaig, Catherine



Mutations in PDGFRB Cause Autosomal-Dominant Infantile Myofibromatosis  

PubMed Central

Infantile myofibromatosis (IM) is a disorder of mesenchymal proliferation characterized by the development of nonmetastasizing tumors in the skin, muscle, bone, and viscera. Occurrence within families across multiple generations is suggestive of an autosomal-dominant (AD) inheritance pattern, but autosomal-recessive (AR) modes of inheritance have also been proposed. We performed whole-exome sequencing (WES) in members of nine unrelated families clinically diagnosed with AD IM to identify the genetic origin of the disorder. In eight of the families, we identified one of two disease-causing mutations, c.1978C>A (p.Pro660Thr) and c.1681C>T (p.Arg561Cys), in PDGFRB. Intriguingly, one family did not have either of these PDGFRB mutations but all affected individuals had a c.4556T>C (p.Leu1519Pro) mutation in NOTCH3. Our studies suggest that mutations in PDGFRB are a cause of IM and highlight NOTCH3 as a candidate gene. Further studies of the crosstalk between PDGFRB and NOTCH pathways may offer new opportunities to identify mutations in other genes that result in IM and is a necessary first step toward understanding the mechanisms of both tumor growth and regression and its targeted treatment.

Martignetti, John A.; Tian, Lifeng; Li, Dong; Ramirez, Maria Celeste M.; Camacho-Vanegas, Olga; Camacho, Sandra Catalina; Guo, Yiran; Zand, Dina J.; Bernstein, Audrey M.; Masur, Sandra K.; Kim, Cecilia E.; Otieno, Frederick G.; Hou, Cuiping; Abdel-Magid, Nada; Tweddale, Ben; Metry, Denise; Fournet, Jean-Christophe; Papp, Eniko; McPherson, Elizabeth W.; Zabel, Carrie; Vaksmann, Guy; Morisot, Cyril; Keating, Brendan; Sleiman, Patrick M.; Cleveland, Jeffrey A.; Everman, David B.; Zackai, Elaine; Hakonarson, Hakon



Endoscopic goniotomy: a potential surgical procedure for primary infantile glaucoma  

NASA Astrophysics Data System (ADS)

Goniotomy is an effective treatment for primary infantile glaucoma. Unlike trabeculotomy, goniotomy facilitates the visualization of the trabecular meshwork and does not disturb the conjunctiva. Because a cloudy cornea may prevent a clear view of the anterior chamber angle through the operating microscope, we investigated whether an endoscope would improve visualization during goniotomy in pig cadaver eyes. We deepened the anterior chamber of each pig eye with viscoelastic material. A modified 23-gauge needle attached to an Olympus 0.8 mm diameter flexible fiberoptic endoscope entered the anterior chamber through a 3 mm limbal incision. The angle was clearly seen on a videoscreen as the needle approached and incised the trabecular pillars for 120 degree(s); the iris immediately fell back. Following the procedure, the eyes were fixed in formalin and sectioned for light microscopy, or fixed in 2% glutaraldehyde for scanning electron microscopy. Trabecular pillars were present from the iris root to Schwalbe's line in the untreated region of the anterior chamber angle. The treated area demonstrated incision of the trabecular pillars with opening of the underlying trabecular meshwork.

Joos, Karen M.; Alward, Wallace L.; Folberg, Robert



Development of infantile rat ovaries autotransplanted after cryopreservation by vitrification.  


We cryopreserved infantile rat ovaries by vitrification and assessed their viability by autotransplantation. Hemilateral ovarian transplantation was performed on rats on postnatal Days 10 to 12. The left ovary of each rat was dissected out, cryopreserved by vitrification using a modified vitrification solution (VS1), and then autotransplanted under the capsule of the right kidney. The right ovary of each rat was removed. For the control, the left ovary was dissected out from each rat and was immediately transplanted by the same procedure, without cryopreservation. Rats were nursed until weaning, and then the day of vaginal opening, estrous cyclicity from the day of vaginal opening until postnatal Day 84, and histology of ovarian grafts at postnatal Day 84 were examined. The time course of development of endocrine function of cryopreserved grafts was similar to that of fresh grafts. In ovarian transplants recovered on postnatal Day 84, antral follicles and corpora lutea (CL) were observed in addition to small follicles, although the number of antral follicles in cryopreserved grafts was smaller than in the fresh grafts. These results indicate that cryopreservation of ovarian tissue by vitrification can be used for the preservation of fertility and endocrine function of ovaries. PMID:10798487

Sugimoto, M; Maeda, S; Manabe, N; Miyamoto, H



Infantile hypertrophic pyloric stenosis in Belfast, 1957-1969.  


Infants with hypertrophic pyloric stenosis born in Belfast during the 13 years 1957-1969 have been reviewed. Their distribution shows a bias towards higher social classes, breast feeding, and primogeniture. Obstetric factors and parental ages seem to be of no importance. More affected infants were born during winter months than would be expected. The overall incidence of infantile pyloric stenosis in this community has fallen during the period under review. Clinically, the patients started vomiting at a mean age of 22 days and it is recommended that the condition should not be called 'congenital'. The size of the tumour is mainly determined by the size of the patient, rather than by his age or duration of symptoms. Attention is drawn to the occurrence of haematemesis in 17-5% and melaena in 2-9% of infants. Jaundice occurred in 1-8% of patients in this series, and is attributed to the adverse effect of starvation on hepatic glucuronyl transferase activity. Other conditions noted in these patients included inguinal hernia, partial thoracic stomach, and phenylketonuria. Subsequent growth and development were in the anticipated range. PMID:1170811

Dodge, J A



A Recurrent PDGFRB Mutation Causes Familial Infantile Myofibromatosis  

PubMed Central

Infantile myofibromatosis (IM) is the most common benign fibrous tumor of soft tissues affecting young children. By using whole-exome sequencing, RNA sequencing, and targeted sequencing, we investigated germline and tumor DNA in individuals from four distinct families with the familial form of IM and in five simplex IM cases with no previous family history of this disease. We identified a germline mutation c.1681C>T (p.Arg561Cys) in platelet-derived growth factor receptor ? (PDGFRB) in all 11 affected individuals with familial IM, although none of the five individuals with nonfamilial IM had mutations in this gene. We further identified a second heterozygous mutation in PDGFRB in two myofibromas from one of the affected familial cases, indicative of a potential second hit in this gene in the tumor. PDGFR-? promotes growth of mesenchymal cells, including blood vessels and smooth muscles, which are affected in IM. Our findings indicate p.Arg561Cys substitution in PDGFR-? as a cause of the dominant form of this disease. They provide a rationale for further investigations of this specific mutation and gene to assess the benefits of targeted therapies against PDGFR-? in aggressive life-threatening familial forms of the disease.

Cheung, Yee Him; Gayden, Tenzin; Campeau, Philippe M.; LeDuc, Charles A.; Russo, Donna; Nguyen, Van-Hung; Guo, Jiancheng; Qi, Ming; Guan, Yanfang; Albrecht, Steffen; Moroz, Brenda; Eldin, Karen W.; Lu, James T.; Schwartzentruber, Jeremy; Malkin, David; Berghuis, Albert M.; Emil, Sherif; Gibbs, Richard A.; Burk, David L.; Vanstone, Megan; Lee, Brendan H.; Orchard, David; Boycott, Kym M.; Chung, Wendy K.; Jabado, Nada



A recurrent PDGFRB mutation causes familial infantile myofibromatosis.  


Infantile myofibromatosis (IM) is the most common benign fibrous tumor of soft tissues affecting young children. By using whole-exome sequencing, RNA sequencing, and targeted sequencing, we investigated germline and tumor DNA in individuals from four distinct families with the familial form of IM and in five simplex IM cases with no previous family history of this disease. We identified a germline mutation c.1681C>T (p.Arg561Cys) in platelet-derived growth factor receptor ? (PDGFRB) in all 11 affected individuals with familial IM, although none of the five individuals with nonfamilial IM had mutations in this gene. We further identified a second heterozygous mutation in PDGFRB in two myofibromas from one of the affected familial cases, indicative of a potential second hit in this gene in the tumor. PDGFR-? promotes growth of mesenchymal cells, including blood vessels and smooth muscles, which are affected in IM. Our findings indicate p.Arg561Cys substitution in PDGFR-? as a cause of the dominant form of this disease. They provide a rationale for further investigations of this specific mutation and gene to assess the benefits of targeted therapies against PDGFR-? in aggressive life-threatening familial forms of the disease. PMID:23731537

Cheung, Yee Him; Gayden, Tenzin; Campeau, Philippe M; LeDuc, Charles A; Russo, Donna; Nguyen, Van-Hung; Guo, Jiancheng; Qi, Ming; Guan, Yanfang; Albrecht, Steffen; Moroz, Brenda; Eldin, Karen W; Lu, James T; Schwartzentruber, Jeremy; Malkin, David; Berghuis, Albert M; Emil, Sherif; Gibbs, Richard A; Burk, David L; Vanstone, Megan; Lee, Brendan H; Orchard, David; Boycott, Kym M; Chung, Wendy K; Jabado, Nada



The natural course of infantile Pompe's disease: 20 original cases compared with 133 cases from the literature  

Microsoft Academic Search

OBJECTIVE: Infantile Pompe's disease is a lethal cardiac and muscular disorder. Current developments toward enzyme replacement therapy are promising. The aim of our study is to delineate the natural course of the disease to verify endpoints of clinical studies. METHODS: A total of 20 infantile patients diagnosed by the collaborative Dutch centers and 133 cases reported in literature were included

Hout van den J. M. P; Ploeg van der A. T; Diggelen van O. P; J. A. M. Smeitink; G. P. A. Smit; B.-T. T. Poll-The; H. D. Bakker; M. C. B. Loonen; J. B. C. de Klerk; A. J. J. Reuser; W. C. J. Hop



Practice Parameter: Medical Treatment of Infantile Spasms Report of the American Academy of Neurology and the Child Neurology Society  

Microsoft Academic Search

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,

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


Primary retroperitoneal malignant melanoma: A case report  

PubMed Central

Primary malignant melanoma occurring at an extra cutaneous site is rare. A case of primary malignant melanoma located in the retroperitoneum of an 18-year-old female is presented in this study. Histopathological examination of the tissue biopsies at laparotomy with immunohistochemical stains confirmed a diagnosis of malignant melanoma. Further extensive clinical and radiological investigations proved the retroperitoneum to be the primary site.




Malignant melanoma of the foot and ankle.  


Malignant melanoma is a serious and devastating skin disease that podiatrists may be called upon to treat. It is pertinent that delays in diagnosis and treatment of malignant melanoma be avoided. Some of the topics discussed in this article are causes, clinical features, classification, and treatment of malignant melanoma, focusing on the foot and ankle. PMID:10810653

John, K J; Hayes, D W; Green, D R; Dickerson, J



Venous thromboembolism in malignant gliomas  

PubMed Central

Summary Malignant gliomas are associated with a very high risk of venous thromboembolism (VTE). While many clinical risk factors have previously been described in brain tumor patients, the risk of VTE associated with newer anti-angiogenic therapies such as bevacizumab in these patients remains unclear. When VTE occurs in this patient population, concern regarding the potential for intracranial hemorrhage complicates management decisions regarding anticoagulation, and these patients have a worse prognosis than their VTE-free counterparts. Risk stratification models identifying patients at high risk of developing VTE along with predictive plasma biomarkers may guide the selection of eligible patients for primary prevention with pharmacologic thromboprophylaxis. Recent studies exploring disordered coagulation, such as increased expression of tissue factor (TF), and tumorigenic molecular signaling may help to explain the increased risk of VTE in patients with malignant gliomas.




Vulvar malignancy in neurofibromatosis syndrome.  


Type 1 neurofibromatosis (NF1) is a dominantly inherited neurologic disorder that affects primarily the skin, bones, and peripheral nervous system. It may be associated with a variety of clinical manifestations including cafe-au-lait spots, skinfold freckling, Lisch nodules, and visceral neurofibromas. Individuals affected by NF1 harbor an increased risk for both benign and malignant tumors. Malignant transformation is usually observed in the form of neurosarcoma. Rarely, NF1 affects the genital tract, and isolated vulvar localization is extremely rare. Here is reported a rare case of a solitary neurosarcoma of the vulva in a 43-year-old woman affected by NF1 syndrome treated with surgical excision. The purpose of this case is to underline the possibility of association between NF1 and genital tract sarcoma and to suggest an accurate evaluation of rapid growth vulvar mass in this setting. PMID:24167749

Musella, Angela; Palaia, Innocenza; Domenici, Lavinia; Casorelli, Assunta; Martoccia, Angela; Benedetti Panici, Pierluigi



Nonepithelial malignancies of the breast.  


Primary nonepithelial malignancies of the breast comprise an important minority of breast neoplasms, including primary breast sarcomas, therapy-related breast sarcomas, the phyllodes tumors, and primary breast lymphomas. With widespread mammographic detection of breast lesions, these tumors represent critical elements of the differential diagnosis of even benign-appearing lesions. Each has a distinct clinical profile, including presentation, available therapeutic options, and prognosis, further underscoring the importance of timely recognition. The increasing incidence of breast carcinomas and the subsequent therapy thereof may be contributing to an increase in the number of therapy-related breast tumors. This review discusses various features of these uncommon malignancies and their treatment, with the goal of increasing understanding of their clinical behavior and management. PMID:15209192

Chugh, Rashmi; Baker, Laurence



[Malignant melanoma and HIV infection].  


Among 1000 patients with HIV infection consecutively examined at our dermatological department during the last 3 years, we diagnosed 4 cases of malignant melanoma. This figure is clearly higher than the statistical incidence of 4-13 cases per 100.000 people a year observed in West Germany. The mean age of our 4 patients and 3 additional cases reported in the literature is 10 years less than the average age found in melanoma patients without HIV infection. These findings indicate an increased risk of malignant melanoma in patients with HIV infection. In most of our patients, the cellular immunity was only marginally impaired, corresponding to the stages WR1 and WR2 (Walter Reed classification). Tumor formation, therefore, does apparently not depend on the severity of decompensation of the immunity. PMID:2528242

Rasokat, H; Steigleder, G K; Bendick, C; Müller, S; Meller, M



Metastatic Malignant Melanoma during Pregnancy  

PubMed Central

Malignant melanoma is one of the most rapidly increasing cancers and, when it occurs during pregnancy, it can frequently metastasise to the placenta and the foetus. Earlier reports suggested a rapid progress of the disease during pregnancy with a poor prognosis; however, recent controlled studies found that stage for stage, the prognosis of melanoma during pregnancy is similar to that in a non-pregnant state. Early diagnosis and prompt treatment can avoid a tragic outcome.

Mathew, Mariam; Sheik, Shahila; Rao, Kuntal; Burney, Ikram A; Sawhney, Sukhpal; Al-Hamdani, Aisha



Malignant odontogenic tumors: an overview  

Microsoft Academic Search

  Abstract\\u000a \\u000a Malignant odontogenic tumors are rare lesions. Only through the gradual accumulation of single cases can one obtain some information\\u000a about their histomorphology, clinical presentation, and behavior. Just as their benign counterparts, they are of epithelial,\\u000a mesenchymal, or mixed nature. Features of the several entities currently recognized are described in this overview.

P. J. Slootweg



GATA Factors in Gastrointestinal Malignancy  

Microsoft Academic Search

GATA factors are unique transcription factors with conserved DNA-binding domains. They serve diverse roles in embryogenesis,\\u000a cell differentiation, regulation of tissue-specific genes, and carcinogenesis. The subfamily GATA-4, -5, and -6 are highly\\u000a expressed in endoderm-derived organs and regulate multiple gut-specific genes. Multiple studies have analyzed the role of\\u000a GATA factors in gastrointestinal (GI) malignancy, such as those of the stomach,

Funmi Ayanbule; Narasimhaswamy S. Belaguli; David H. Berger



Malignant glioma: neuropathology and neurobiology.  


Malignant gliomas may manifest at any age including congenital and childhood cases. Peak incidence is, however, in adults older than 40 years. Males are more frequently affected than females. The sole unequivocal risk factor is therapeutic ionizing irradiation. Malignant gliomas comprise a spectrum of different tumor subtypes. Within this spectrum, glioblastoma, anaplastic astrocytoma and anaplastic oligodendroglioma share as basic features preferential location in cerebral hemispheres, diffuse infiltration of brain tissue, fast tumor growth with fatal outcome within months or years. Invasion is regarded as one of the main reasons for poor therapeutic success, because it makes complete surgical removal of gliomas impossible. Invasion of glioma cells requires interaction with the extracellular matrix and with surrounding cells of the healthy brain tissue. Vascular proliferates and tissue necrosis are characteristic features of malignant gliomas, in particular glioblastoma. These features are most likely the consequence of rapidly increasing tumor mass that is inadequately oxygenized by the preexisting vasculature. In malignant glioma, distinct molecular pathways including the p53 pathway, the RB pathway and the EGFR pathway show frequent alterations that seem to be pathogenetically relevant. Methylguanine-methyltransferase (MGMT) promoter methylation status in glioblastoma and 1p19q deletion status in anaplastic oligodendroglioma are associated with response to chemotherapy. The role of neuropathology and neurobiology in neurooncology is 1. to provide a clinically meaningful classification of brain tumors on basis of pathobiological factors, 2. to clarify etiology and pathogenesis of brain tumors as rational basis for development of new diagnostic tests and therapies, and 3. to translate testing for new clinically relevant molecular parameters into clinical application. PMID:16944363

Preusser, Matthias; Haberler, Christine; Hainfellner, Johannes A



Palliation of Malignant Obstructive Jaundice  

Microsoft Academic Search

Peri-ampullary and hepatic malignancies will frequently present with obstructive jaundice. For unresectable tumors, effective\\u000a and lasting decompression of the biliary tree is essential to improve quality of life and survival. An overview of present\\u000a treatment modalities for palliation of obstructive jaundice is provided, including a systematic review of the English literature\\u000a regarding the optimum choice of palliation.

G. Garcea; S. L. Ong; A. R. Dennison; D. P. Berry; G. J. Maddern



Endoplasmic reticulum stress in malignancy.  


The combination of relative nutrient deprivation and dysregulation of protein synthesis make malignant cells especially prone to protein misfolding. Endoplasmic reticulum stress, which results from protein misfolding within the secretory pathway, has a profound effect on cancer cell proliferation and survival. In this review, we examine the evidence implicating endoplasmic reticulum dysfunction in the pathology of cancer and discuss how recent findings may help to identify novel therapeutic targets. PMID:24823636

Clarke, Hanna J; Chambers, Joseph E; Liniker, Elizabeth; Marciniak, Stefan J



Randomised controlled trial of infantile colic treated with chiropractic spinal manipulation  

PubMed Central

AIMS—To investigate the efficacy of chiropractic spinal manipulation in the management of infantile colic.?METHODS—One hundred infants with typical colicky pain were recruited to a randomised, blinded, placebo controlled clinical trial.?RESULTS—Nine infants were excluded because inclusion criteria were not met, and five dropped out, leaving 86 who completed the study. There was no significant effect of chiropractic spinal manipulation. Thirty two of 46 infants in the treatment group (69.9%), and 24of 40 in the control group (60.0%), showed some degree of improvement.?CONCLUSION—Chiropractic spinal manipulation is no more effective than placebo in the treatment of infantile colic. This study emphasises the need for placebo controlled and blinded studies when investigating alternative methods to treat unpredictable conditions such as infantile colic.??

Olafsdottir, E; Forshei, S; Fluge, G; Markestad, T



The Problem of Atypical Neuroleptic Malignant Syndrome  

PubMed Central

Neuroleptic malignant syndrome is a serious and potentially fatal adverse effect of antipsychotic medications. Although diagnostic criteria for neuroleptic malignant syndrome have been established and are widely accepted and used, it should be recognized that atypical presentations occur, particularly during treatment with atypical antipsychotics. However, it remains unclear whether these atypical presentations represent early or impending neuroleptic malignant syndrome. Furthermore, since neuroleptic malignant syndrome is a diagnosis of exclusion, careful consideration of other neuropsychiatric conditions should occur. Relying on creatine phosphokinase elevation may result in an incorrect diagnosis of atypical neuroleptic malignant syndrome. We wish to present a case of this diagnostic dilemma in a patient with catatonia.

Surber, Susan A.



Primary oral malignant melanoma: case report.  


Primary oral malignant melanoma usually presents as a dark brown or black lesion. It is a rare malignancy, accounting for less than 1% of all melanomas and 1.6% of all head and neck malignancies, thus forming up to 0.5% of all oral malignancies in the world literature. In general, the prognosis of oral melanoma is poor and worse than that of cutaneous melanoma. The preferred treatment is radical surgery alone or in combination with radiotherapy, chemotherapy, immunotherapy and immunomodulatory agents. A case is presented of a large malignant melanoma of oral cavity, noticed six months before initial biopsy and by history described as a rapidly growing mass. PMID:20635585

Bujas, Tatjana; Pavi?, Ivana; Prus, Andrej; Marusi?, Zlatko; Balicevi?, Drinko



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


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

Marrè-Brunenghi, G; Camoriano, R; Valle, M; Boero, S



Infantile cortical hyperostosis (Caffey disease): a possible misdiagnosis as physical abuse.  


Infantile cortical hyperostosis (Caffey disease) is a rare self-limiting inflammatory bony disease of early infancy. We report a 1-month-old Chinese boy with Caffey disease who presented with painful swelling over his shins bilaterally. Physical abuse was initially suspected, but the radiological findings of periosteal thickening over multiple bones (particularly the mandible), symmetrical involvement, diaphyseal involvement with sparing of the epiphysis, made Caffey disease a likely diagnosis. This report highlights that infantile cortical hyperostosis is an important differential diagnosis for children suspected of being abused, and clinicians should have a high index of suspicion to avoid misdiagnosis. PMID:20890006

Lo, Henny P W; Lau, H Y; Li, C H; So, K T



Malignant migrating partial seizures in infancy.  


A previously unreported epileptic condition characterised by onset before 6 months of age, nearly continuous electroencephalographic seizures involving multiple independent areas originating in both hemispheres, no identifiable cause, and poor outcome has been described by Coppola et al. We report three cases presenting the same clinical and EEG pictures. They show a peculiar epileptic condition unlike the other early epileptogenic encephalopathies, so they may represent a new infantile epileptic syndrome. PMID:11395285

Veneselli, E; Perrone, M V; Di Rocco, M; Gaggero, R; Biancheri, R



Identification of serum regression signs in infantile hemangioma.  


Vessel proliferation underlies a number of serious pathological conditions. Infantile Hemangioma (IH) is a low-aggressive vascular tumor, interesting as an in vivo model of spontaneous tumor regression. Identifying mechanisms underlying IH spontaneous regression may then help to elucidate vessel-growth control, strongly deregulated in other serious conditions such as sarcoma, melanoma, diabetic retinopathy. The present study was aimed at identifying early regression indicators within hematological parameters. Thirty-four blood samples were collected from IH diagnosed babies (20-months median age), spontaneously regressing with age. Nineteen serum standard blood-tests were carried out using diagnostic reagents; in addition, serum-expression of 27 cytokine/chemokines was measured. Samples were divided in three age-groups, namely ? 12, 13 to 24 and >24 months-age, respectively. Red-cells count, Hemoglobin, Hematocrit, Neutrophils, Lymphocytes, MCP-1 and MIP-1beta were significantly different in the three age-groups, according to one-way ANOVA analysis. The same parameters showed a significant Pearson-correlation with age, supporting the direct link of age with IH-regression. ROC analysis showed that red-cells count, Hemoglobin, Hematocrit, MCP-1 and MIP-1beta levels significantly discriminate IH in the proliferating-phase from IH in the regressing-phase. Such data indicate for the first time that standard hematological tests and cytokine serum-expression values may effectively discriminate proliferating- from regressing-IH, unrevealing early regression signs, and demonstrate that standard blood-tests may have novel unsuspected diagnostic/prognostic relevance in altered vessel-growth conditions. PMID:24599340

D'Arcangelo, Daniela; Nicodemi, Ezio M; Rossi, Stefania; Giampietri, Claudia; Facchiano, Francesco; Facchiano, Antonio



PRRT2 links infantile convulsions and paroxysmal dyskinesia with migraine  

PubMed Central

ABSTRACT Objective: Whole genome sequencing and the screening of 103 families recently led us to identify PRRT2 (proline-rich-transmembrane protein) as the gene causing infantile convulsions (IC) with paroxysmal kinesigenic dyskinesia (PKD) (PKD/IC syndrome, formerly ICCA). There is interfamilial and intrafamilial variability and the patients may have IC or PKD. Association of IC with hemiplegic migraine (HM) has also been reported. In order to explore the mutational and clinical spectra, we analyzed 34 additional families with either typical PKD/IC or PKD/IC with migraine. Methods: We performed Sanger sequencing of all PRRT2 coding exons and of exon-intron boundaries in the probands and in their relatives whenever appropriate. Results: Two known and 2 novel PRRT2 mutations were detected in 18 families. The p.R217Pfs*8 recurrent mutation was found in ?50% of typical PKD/IC, and the unreported p.R145Gfs*31 in one more typical family. PRRT2 mutations were also found in PKD/IC with migraine: p.R217Pfs*8 cosegregated with PKD associated with HM in one family, and was also detected in one IC patient having migraine with aura, in related PKD/IC familial patients having migraine without aura, and in one sporadic migraineur with abnormal MRI. Previously reported p.R240X was found in one patient with PKD with migraine without aura. The novel frameshift p.S248Afs*65 was identified in a PKD/IC family member with IC and migraine with aura. Conclusions: We extend the spectrum of PRRT2 mutations and phenotypes to HM and to other types of migraine in the context of PKD/IC, and emphasize the phenotypic pleiotropy seen in patients with PRRT2 mutations.

Cloarec, Robin; Bruneau, Nadine; Rudolf, Gabrielle; Massacrier, Annick; Salmi, Manal; Bataillard, Marc; Boulay, Clotilde; Caraballo, Roberto; Fejerman, Natalio; Genton, Pierre; Hirsch, Edouard; Hunter, Alasdair; Lesca, Gaetan; Motte, Jacques; Roubertie, Agathe; Sanlaville, Damien; Wong, Sau-Wei; Fu, Ying-Hui; Rochette, Jacques; Ptacek, Louis J.



Visual Acuity Development of Children with Infantile Nystagmus Syndrome  

PubMed Central

Purpose. Infantile nystagmus syndrome (INS) can be idiopathic or associated with ocular or systemic disease. The ocular oscillation of INS directly contributes to loss of visual acuity. In this study, visual acuity development in patients with INS was examined. Methods. Children with INS were classified as having idiopathic INS (n = 84) or INS with an associated sensory deficit: INS and albinism (n = 71), bilateral optic nerve hypoplasia (ONH; n = 23), or congenital retinal disorder (n = 36). Visual acuity was assessed with Teller cards and/or optotypes, and the data were analyzed for three age groups (<24 months, 24–48 months, and >48 months). Results. Patients with idiopathic INS showed mildly reduced visual acuity early in life and gradual maturation with age that paralleled a normative curve. Patients with albinism also showed a mild visual deficit early in life but failed to keep pace with the normative curve, showing a gradual increase in visual acuity deficit. Patients with ONH and congenital retinal disorders exhibited more severe visual acuity deficits during infancy. The ONH group displayed slow improvement of visual acuity with a plateau at 24 months through >48 months, with a small increase in visual acuity deficit. The congenital retinal disorder group had no significant change in visual acuity across age and had a rapid increase in visual acuity deficit. Conclusions. The pattern of visual acuity development differs among children with INS, depending on the presence or absence of associated sensory system deficits. Careful characterization of visual system differences in patients with INS is important if visual acuity is an outcome in clinical trials.

Bilonick, Richard A.; Felius, Joost; Hertle, Richard W.; Birch, Eileen E.



How Airway Venous Malformations Differ From Airway Infantile Hemangiomas  

PubMed Central

Objective To compare airway infantile hemangiomas (IHs) and venous malformations (VMs) clinically, radiographically, endoscopically, and histologically. Design Retrospective cohort study. Setting Tertiary care pediatric hospital. Patients The study included patients seen in the Vascular Anomaly Clinic, Seattle Children’s Hospital, Seattle, Washington, between 2001 and 2008. Methods All patients with airway vascular anomalies were identified by searching the Vascular Anomaly Quality Improvement Database and hospital discharge data. The data, which were analyzed with descriptive statistics and the Fisher exact test, included presenting age, sex, presenting signs, lesion site, and radiographic, endoscopic, and histologic findings.. Results Seventeen patients with airway lesions were identified, 6 with VMs and 11 with IHs. Patients with VMs presented at a mean (SD) age of 11.3 (13.7) months (age range, 3–39 months), while those with IHs presented at 3 (1.8) months of age (age range, 1–6 months) (P =.03). The patients with IHs were predominantly female (9 of 11 [81%]), while no sex difference was noted among the patients with VMs (3 of 6 [50%]). All patients with IHs presented with stridor and cutaneous lesions, whereas patients with VMs more often presented with hemoptysis or dysphagia (P = .001). Computed tomographic angiograms demonstrated enhancing endolaryngeal lesions in all IHs, while VMs enhanced poorly. Endoscopically, IHs were transglottic, while VMs were postcricoid or epiglottic (P <.001). Histologically, immunostained lesions showed submucosal lobules of capillaries lined by GLUT-1 (glucose transporter isoform 1)–positive endothelium in IHs, whereas VMs consisted of loosely organized venous channels that lacked GLUT-1 staining. Conclusion Patients with airway IHs and VMs differ in presenting age and signs, sex, airway lesion location, enhancement on computed tomographic angiograms, and histologic appearance.

Parhizkar, Nooshin; Manning, Scott C.; Inglis, Andrew F.; Finn, Laura S.; Chen, Eunice Y.; Perkins, Jonathan A.



Infantile postoperative encephalopathy: perioperative factors as a cause for concern.  


We report on 6 infants who underwent elective surgery and developed postoperative encephalopathy, which had features most consistent with intraoperative cerebral hypoperfusion. All infants were <48 weeks' postmenstrual age and underwent procedures lasting 120 to 185 minutes. Intraoperative records revealed that most of the measured systolic blood pressure (SBP) values were <60 mm?Hg (the threshold for hypotension in awake infants according to the Pediatric Advanced Life Support guidelines) but that only 11% of the measured SBP values were <1 SD of the mean definition of hypotension (<45 mm?Hg) as reported in a survey of members of the Society for Pediatric Anesthesia in 2009. Four infants also exhibited prolonged periods of mild hypocapnia (<35 mm?Hg). One infant did not receive intraoperative dextrose. All infants developed new-onset seizures within 25 hours of administration of the anesthetic, with a predominant cerebral pathology of supratentorial watershed infarction in the border zone between the anterior, middle, and posterior cerebral arteries. Follow-up of these infants found that 1 died, 1 had profound developmental delays, 1 had minor motor delays, 2 were normal, and 1 was lost to follow-up. Although the precise cause of encephalopathy cannot be determined, it is important to consider the role that SBP hypotension (as well as hypoglycemia, hyperthermia, hyperoxia, and hypocapnia) plays during general anesthesia in young infants in the development of infantile postoperative encephalopathy. Our observations highlight the lack of evidence-based recommendations for the lower limits of adequate SBP and end-tidal carbon dioxide in anesthetized infants. PMID:24515520

McCann, Mary Ellen; Schouten, A N J; Dobija, Nicole; Munoz, Carlos; Stephenson, Lianne; Poussaint, Tina Y; Kalkman, C J; Hickey, Paul R; de Vries, Linda S; Tasker, Robert C



Behavioral profiles of children with infantile nephropathic cystinosis.  


Children with infantile nephropathic cystinosis have evidence of visuospatial and arithmetic deficits on a background of normal intellectual and verbal skills. This study aimed to define further their behavioral phenotype. The Achenbach Child Behavior Checklist was completed by parents of: 64 children and adolescents with cystinosis (33 females, 31 males; mean age 8 y 8 mo, range 4 to 16y, SD 2 y 11 mo); 101 healthy controls (47 females, 54 males; mean age 8 y 4 mo, range 4 to 16 y, SD 2 y 11 mo); 21 children and adolescents with cystic fibrosis (CF), termed chronic-disease controls (9 females, 12 males; mean age 11 y 3 mo, age range 4 to 17 y, SD 3 y 5 mo). Compared with healthy controls, individuals with cystinosis had evidence of a significantly higher incidence of behavioral problems, including social problems, somatic complaints, and attention problems. Compared with the chronic-disease control group, the cystinosis group differed only on the Social Problems scale, with 22% of participants with cystinosis scoring in the 'at risk' range whereas no participant with CF received an elevated score on this scale. We conclude that children and adolescents with cystinosis have evidence of a significant incidence of social difficulties compared with individuals with another chronic illness and healthy participants. The combination of visuospatial problems, difficulty with arithmetic, attention problems, and social difficulties seen in the cystinosis group constitutes a behavioral phenotype of this genetic disorder. This cluster of cognitive and behavioral symptoms is also seen in the nonverbal learning disabilities syndrome, and suggests a possible early difference in brain development in children with cystinosis compared with children who do not share this genetic disorder. PMID:15938069

Delgado, Gustavo; Schatz, Amy; Nichols, Sharon; Appelbaum, Mark; Trauner, Doris



Proteomic analysis on infantile spasm and prenatal stress.  


Infantile spasms (IS) are an age-dependent epileptic encephalopathy with severe cognitive dysfunction. Prenatal stress (PS) has been reported to increase the risk for IS through clinical and animal studies. We aim to investigate the mechanism of brain damage caused by IS and the effect of PS. Animals were divided into 4 groups: PS-spasm model, PS-saline control, NS-spasm model, and saline control. N-methyl-d-aspartate (NMDA) was used to induce spasm and swimming in cold water was used to induce PS. A proteomics-based approach was used to compare the NS-spasm model vs. saline control, and PS-spasm model vs. NS-spasm model. Gel image analysis was followed by mass spectrometric protein identification and bioinformatics analysis. We observed an increased spasm frequency (t=8.65, P<0.001), and a shorter latency period (t=3.96, P<0.001) in the PS-spasm model vs. the NS-spasm model. In the NS-spasm model vs. saline control, the main differentially expressed proteins were CFL1, PKM2, PRPS2, DLAT, CKB, DPYSL3, and SNAP25. In the PS-spasm model vs. NS-spasm model, MDH1 and YWHAZ were differentially expressed. YWHAZ was directly connected with CFL1 in protein networks. YWHAZ and CFL1 were further validated by Western blot analysis. The biological function of differentially expressed proteins indicates the pathogenesis of IS maybe relevant to energy metabolism, brain development, and neural remodeling. PS aggravated seizures in the NMDA-induced spasm model, YWHAZ, and CFL1 may be involved. PMID:24994451

Wang, Jing; Wang, Juan; Zhang, Ying; Yang, Guang; Shang, Ai-Jia; Zou, Li-Ping



Second Malignancies Among Elderly Survivors of Cancer  

PubMed Central

The U.S. population is aging, life expectancy is increasing, and cancer is a disease associated with aging. Advances in screening and therapeutics have led to a growing number of cancer survivors who are at risk for the development of secondary malignancies. Although the risks for the development of second malignancies following a first diagnosis of cancer are well described for survivors of childhood malignancies, there are fewer data for malignancies common in older adults. With the aging of the U.S. population, and with improving survival statistics in many adult malignancies, there is an increasing need to identify those second malignancies that might develop in the older adult survivor of cancer. In this paper, we describe the types and rates of second malignancies following cancers commonly seen in older adults and review the literature on these malignancies. Comparisons are made between older and younger adults with regard to the risks for developing treatment-related cancers with different modalities. Recommendations for early detection of second malignancies are summarized, though there remains an unmet need for evidence-based guidelines for screening for second malignancies in the older adult in particular.

Hurria, Arti



Targeted therapy in gastrointestinal malignancies  

PubMed Central

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.

Chhatrala, Ravi; Thanavala, Yasmin; Iyer, Renuka



Malignant Neoplasms of the Nasopharynx  

PubMed Central

A mass in the neck, facial pain and cranial nerve palsies are the most common presenting symptoms of malignant tumours of the nasopharynx. Surgery is limited to biopsy for histological diagnosis. External irradiation is the treatment of choice, both for the primary lesion and the regional and distant metastases. Illustrative case histories are presented in detail. Experience over a 20-year period demonstrates that a 20% five-year survival rate has been obtained. ImagesFig. 1Fig. 2Fig. 3Fig. 4Fig. 5Fig. 6Fig. 7Fig. 8

Novick, W. H.; Shimo, G.; Ryder, D. R.; Pirozynski, W. J.; Hazel, J. J.; Bouchard, J.



Immune therapies for malignant mesothelioma.  


Malignant mesothelioma (MM) is a rare disease which can develop in pleura, pericardium or peritoneum and in which the therapies available have limited efficacy and are associated with various side effects. Therefore, there is a need for more targeted and more effective therapies which are able to halt the disease progression. Among them immune therapies actively or passively directed against various structures of the MM cells seem to be particularly promising given their inhibitory potential demonstrated in both experimental and early clinical studies. Mesothelin in particular seem to be not only a biomarker of disease activity but also a therapeutic target. This review discusses the immune therapies currently investigated for MM. PMID:24833011

Antoniu, Sabina Antonela; Dimofte, Gabriel; Ungureanu, Didona



The psychosocial aspects of malignancy.  


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

Kriesel, H T



Malignant Tumours Following Immunosuppressive Therapy  

PubMed Central

Two cases of malignant disease occurring during immunosuppressive therapy, one a leiomyosarcoma of bowel metastatic to the liver, the other, carcinoma in situ of the cervix uteri, are reported. The possible roles of immunosuppression and immunosuppressive therapy in the pathogenesis of these neoplasms are discussed. It is suggested that the incidence of neoplasms in immunologically suppressed patients is greatly increased and that further investigation into the relation of immunosuppression to cancer is urgently needed. ImagesFIG. 1FIG. 2FIG. 3FIG. 4

Pritzker, K. P. H.; Huang, S. N.; Marshall, K. G.



Malignant schwannoma of kidney capsule.  


This report is of a malignant schwannoma originating in the capsule of the right kidney. Using sonography, nephroangiography, cavography, computer tomography, and bone scanning, metastases in the kidney or a retroperitoneal tumor could be diagnosed. After transperitoneal exploration, the right kidney and mesenteric metastases were removed. Due to tumor infiltration into the liver and tumor masses in the retroperitoneum, only nephrectomy and palliative excision of retroperitoneal metastases were done. Pulmonary metastases developed postoperatively, and the patient died three months after the operation. PMID:1279879

Romics, I; Bach, D; Beutler, W



Malignant paraganglioma: a case report.  


A paraganglioma is a rare tumour composed of chromaffin cells. The malignant paraganglioma is a very rare presentation, diagnosed by local recurrence after total resection of primary mass or findings of distant metastasis. Recurrent paraganglioma developed in a 60 years old lady 10 years after first surgical resection. This time the patient presented with neck swelling as well as with vertebral metastases. The patient underwent radiotherapy and symptomatic improvement was there. We present the case to emphasize the role of imaging in early diagnosis, avoidance of complications of advanced disease and to make awareness among the physicians. PMID:24858172

Doza, F; Majumder, A S; Rahman, M M; Akhter, M Q; Nahar, K; Hossain, M F



Role of subcortical structures in the pathogenesis of infantile spasms: What are possible subcortical mediators?  

Microsoft Academic Search

Infantile spasms present a constellation of symptoms and laboratory findings that suggest a role of subcortical circuits in the pathogenesis of this illness. The clinical features of spasms and the influence of subcortical circuits in the regulation of the electroencephologram, along with frequent abnormalities in subcortical structure and functional anatomy, brain stem electrophysiology, sleep regulation, and subcortical neurotransmitter levels, point

F. A. Lado; S. L. Moshé



Bronchoalveolar Cell Profiles in Children with Asthma, Infantile Wheeze, Chronic Cough, or Cystic Fibrosis  

Microsoft Academic Search

Differential cell counts of bronchoalveolar lavage (BAL) have been reported in normal children but few data on cellular profiles in bronchial diseases in childhood are available. We determined the BAL cell profiles of 72 children divided into 5 groups: asthma (n 5 14), chronic cough (n 5 12), infantile wheeze (n 5 26), cystic fibrosis (n 5 10), and control



Neuropsychological Findings in High-Functioning Men with Infantile Autism, Residual State  

Microsoft Academic Search

Ten men (ages 18–39) with clear histories of Infantile autism and approximately average verbal and nonverbal intelligence were studied with a comprehensive battery of neuropsychological tests. Comparisons with 10 matched normal controls showed no significant differences in many visuoperceptual or memory skills or in sensory-perceptual or motor skills or their lateralization. Differences seen on language measures were small, but statistically

Judith M. Rumsey; Susan D. Hamburger



A comparison of five diagnostic systems for childhood schizophrenia and infantile autism  

Microsoft Academic Search

Five diagnostic systems designed to differentiate infantile autism and early childhood schizophrenia were compared by deriving scores on 44 children referred consecutively to the same clinical center. While the autistic scales devised by Rimland, Polan and Spencer, Lotter, and the British Working Party correlated significantly, the degree of correspondence (35%) indicated that several children obtained high autistic scores in one

Marian K. DeMyer; Don W. Churchill; William Pontius; Katherine M. Gilkey




Microsoft Academic Search

he conventional osteotomies used to treat infantile tibia vara (Blount's disease) may require internal fixation and its subsequent removal. These techniques, which carry the risk of traction injury, and potential problems of stability and consolidation, do not always succeed in correcting the rotational deformity which accompanies the angular deformity. We have used a new surgical approach, the serrated W\\/M osteotomy

S. Hayek; E. Segev; E. Ezra; F. Lokiec; S. Wientroub


DTI registration in atlas based fiber analysis of infantile Krabbe disease  

Microsoft Academic Search

In recent years, diffusion tensor imaging (DTI) has become the modality of choice to investigate white matter pathology in the developing brain. To study neonate Krabbe disease with DTI, we evaluate the performance of linear and non-linear DTI registration algorithms for atlas based fiber tract analysis. The DTI scans of 10 age-matched neonates with infantile Krabbe disease are mapped into

Yi Wang; Aditya Gupta; Zhexing Liu; Hui Zhang; Maria L. Escolar; John H. Gilmore; Sylvain Gouttard; Pierre Fillard; Eric Maltbie; Guido Gerig; Martin Styner



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

ERIC Educational Resources Information Center

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…

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



Morphological approaches to the prenatal diagnosis of late-infantile and juvenile Batten disease  

Microsoft Academic Search

The morphological approach to prenatal diagnosis of late-infantile (LIB) and juvenile (JB) Batten disease is based on observations on known lysosomal storage diseases. In Pompe disease, uncultured amniotic fluid cells show lysosomal storage of glycogen; and in most lysosomal disorders in which there is visceral involvement, the placenta shows evidence of storage in the appropriate cell types. In many instances

B. D. Lake



The leukoencephalopathy of infantile GM1 gangliosidosis: oligodendrocytic loss and axonal dysfunction  

Microsoft Academic Search

A myelin deficit in the cerebral white matter in infantile GM1 gangliosidosis is well established. Some have proposed this deficit to be secondary to axonal loss, while others argue for delayed or arrested myelination. We compared the frontal white and gray matter of two infants with GM1 gangliosidosis with four age-matched controls, using light microscopy with a quantitative analysis, immunohistochemistry,

J. Patrick van der Voorn; Wout Kamphorst; Marjo S. van der Knaap; James M. Powers



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

ERIC Educational Resources Information Center

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…

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



Beliefs regarding the etiology and treatment of infantile diarrhea in Lima, Peru  

Microsoft Academic Search

Three groups of women in Lima, Peru, were interviewed regarding their beliefs about the etiology and treatment of infantile diarrhea. The first group consisted of 91 mothers of children under the age of 2. These were interviewed at two locations: the pediatric emergency service of a teaching hospital serving northern Lima and a health center located in one of the

Gabriel J. Escobar; Eduardo Salazar; Mario Chuy



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


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

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



Infantile autism: A total population study of reduced optimality in the pre-, peri-, and neonatal period  

Microsoft Academic Search

Twenty-five autistic children, constituting a total population sample of children with infantile autism, were compared with 25 sex- and maternityclinic-matched controls for occurrence of reduced optimality in the pre-, peri-, and neonatal period, as noted in medical records. Autistic children showed greatly increased scores for reduced optimality, especially with regard to prenatal factors. The findings are at odds with early

Christopher Gillberg; I. Carina Gillberg



Microcephaly with Simplified Gyration, Epilepsy, and Infantile Diabetes Linked to Inappropriate Apoptosis of Neural Progenitors  

Microsoft Academic Search

We describe a syndrome of primary microcephaly with simplified gyral pattern in combination with severe infantile epileptic encephalopathy and early-onset permanent diabetes in two unrelated consanguineous families with at least three affected children. Linkage analysis revealed a region on chromosome 18 with a significant LOD score of 4.3. In this area, two homozygous nonconserved missense mutations in immediate early response

Rachel Schot; Marta Jones; Hanka Venselaar



Infantile-Onset Diabetes Mellitus: A 1Year Follow-up Study  

Microsoft Academic Search

This study evaluates the clinical profiles and outcomes of children with infantile-onset diabetes mellitus (IODM) (onset at <1 year). Twelve infants with IODM presenting to our hospital from January 2003 to December 2007 are analyzed. All undergo thorough history, clinical examination, and investigations and are managed as per hospital-approved protocol and periodically followed up. Of 12 infants (3 boys and

Ramaswamy Ganesh; Ravindrakumar Arvindkumar; Thiruvengadam Vasanthi



Use of propranolol in infantile haemangiomas: report of five cases and review of the literature  

PubMed Central

Infantile haemangiomas are common benign tumours that do not require treatment unless they cause significant functional impairment or disfigurement. We report our experience with the off-label use of propranolol in 5 children with haemangiomas and review the relevant literature.

Gidaris, D; Economou, M; Hatzidemetriou, V; Gombakis, N; Athanassiou - Metaxa, M



XXY: The Hidden Disability and a Prototype for an Infantile Presentation of Developmental Dyspraxia (IDD).  

ERIC Educational Resources Information Center

There is an increased incidence of language-learning disabilities with dyslexia by school age. As infants and toddlers, these children have neuromotor and speech dysfunction within their first year. This article postulates that the language and motor dysfunction is caused by infantile presentation of developmental dyspraxia rather than a…

Samango-Sprouse, Carole; Rogol, Alan



Infantile hemangioma is a proliferation of LYVE-1-negative blood endothelial cells without lymphatic competence  

Microsoft Academic Search

Infantile hemangiomas are common benign vascular tumors that exhibit a characteristic history of rapid proliferation in the first year of life and slow spontaneous involution during early childhood. The causative pathogenic event responsible for the abnormal endothelial proliferation remains elusive. The recent discovery of an immature phenotype of proliferating hemangioma endothelial cells due to the exclusive expression of the lymphatic

Van An Nguyen; Heinz Kutzner; Christina Fürhapter; Alexandar Tzankov; Norbert Sepp



The Empty Fortress; Infantile Autism and the Birth of the Self.  

ERIC Educational Resources Information Center

The nature, origin, and treatment of infantile autism are explored with a consideration of the child's world of encounter and case histories. The beginning of life, called the region of shadows, is mentioned; and the world of the newborn, body language, mutuality, autonomy, the autistic anlage, and the right side of time are examined for the…

Bettelheim, Bruno


Early infantile epileptic encephalopathy: a long-term follow-up study  

Microsoft Academic Search

The authors describe the eletroclinical aspects and long-term evolution of five (in one male and four female patients) cases of early infantile epileptic encephalopathy. In the neonatal period, the most common seizures were tonic spasms (either generalized or lateralized) that, very often, occurred in series. All newborns showed the typical suppression-burst pattern. The neurological status (initially normal) progressively deteriorated in

A. Verrotti; S. Domizio; G. Sabatino; G. Morgere



Infección respiratoria aguda en niños que acuden a un centro de desarrollo infantil  

Microsoft Academic Search

Objective. To assess the incidence of acute respiratory in- fections and bacterial colonization in children attending a daycare center. Material and Methods. A cohort study was conducted from April to Octuber 1999, among 85 chil- dren aged under four years, who attended the daycare center at Hospital Infantil de Mexico (Mexico City's Children's Hospital) \\

Eugenia Nandí-Lozano; Luz Elena Espinosa; Lucía Viñas-Flores; Carlos Avila-Figueroa



Epidemiology of Infantile Hydrocephalus in Saudi Arabia: Birth Prevalence and Associated Factors  

Microsoft Academic Search

Introduction: Hydrocephalus is a common central nervous system disorder in children. In spite of its importance, it has not been subjected to sufficient epidemiological studies, particularly in the developing countries. The aim of this study was to provide information from a representative series of newly diagnosed cases of infantile hydrocephalus on the birth prevalence, associated factors and mortality. Methodology: A

Waleed Rida Murshid; Jamal Saleh Jarallah; Mohammad Imam Dad



Co-Development of VEP Motion Response and Binocular Vision in Normal Infants and Infantile Esotropes  

Microsoft Academic Search

PURPOSE. To determine the maturational course of nasotemporal asymmetry in infantile esotropia and to define the relationships among the symmetry of the motion visual evoked potential (MVEP), eye alignment, fusion, and stereopsis. METHODS. Sixty healthy term infants and 34 infants with esotropia participated. Nasotemporal MVEP asymmetry was assessed by the presence of a significant F1 response component with an inter-

Eileen E. Birch; Sherry Fawcett; David Stager



Epidemiology of Infantile Autism in Southern Ibaraki, Japan: Differences in Prevalence in Birth Cohorts.  

ERIC Educational Resources Information Center

Based on an observational study of children (ages 3-7) screened at a child guidance center in Japan, the prevalence rate of infantile autism in each one-year birth cohort (1972-1978) fluctuated in a four-year cycle which was closely correlated with the number of children hospitalized with lower respiratory tract diseases. (JW)

Tanoue, Yoko; And Others



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

ERIC Educational Resources Information Center

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…

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



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

PubMed Central

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.

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



Systematic review of the occurrence of infantile colic in the community  

PubMed Central

AIMS—To assess the occurrence of infantile colic in the community and the need for professional help; and to study the influences of potential determinants of infantile colic.?METHODS—Surveys were identified by a systematic search in Medline (1966-98) and Embase (1988-98). Retrieved publications were checked for references. Studies selected were community based, prospective, and retrospective surveys on the occurrence of infantile colic published in English, German, French, or Dutch. Occurrence rates were calculated as percentages. Methodological quality of the surveys was assessed by two assessors independently with a standardised criteria list containing items on method of data gathering, definition of colic, and drop out rate.?RESULTS—Fifteen community based surveys were identified. The methodological quality varied considerably and was generally low. Even the two most methodologically sound prospective studies yielded widely varying cumulative incidence rates of 5-19%. Referral rates or the need to seek help because of crying were consistently lower than occurrence rates for prolonged crying as such. Gender, socioeconomic class, type of feeding, family history of atopy, and parental smoking were not shown to be associated with colic.?CONCLUSION—Occurrence rates of infantile colic vary greatly according to methodological quality. A considerable number of parents reporting prolonged crying do not seek or need professional help.??

Lucassen, P; Assendelft, W; van Eijk, J T. M; Gubbels, J; Douwes, A; van Geldrop, W J



Body Mass Index in Male and Female Children with Infantile Autism.  

ERIC Educational Resources Information Center

This study compared the body mass index (BMI) of 118 children with infantile autism with corresponding BMI percentiles in age-and sex-matched reference populations. The BMI distribution of the male children was significantly lower than that of the age-matched reference population. BMI was not associated with intelligence or socioeconomic status.…

Mouridsen, Svend Erik; Rich, Bente; Isager, Torben



Dolichol biosynthesis in human malignant cells.  

PubMed Central

Cholesterol, ubiquinone and dolichol biosynthesis from mevalonic acid was measured in non-malignant and malignant cultured human lymphocytes, freshly isolated human mononuclear leucocytes and in cultured human hepatoma cells. The relative flux of mevalonate into ubiquinone, dilichol and cholesterol was not significantly different between malignant and non-malignant cells, although the extent of labelling of each product was an order of magnitude greater in the malignant cultured cells. The most prominent dolichol isolated from total cellular lipid and synthesized in short-term labelling of cultured leukaemic cells had a chain length one isoprene unit shorter than that observed in normal human cells. Cultured human hepatoma cells and mononuclear leucocytes isolated from the peripheral blood of individuals with lymphoblastic and myelogenic leukaemia similarly synthesized shorter-chain dolichols. The dolichols made in cultured non-tumorigenic cells, freshly isolated mononuclear leucocytes from a normal individual or a patient with non-haematological malignancy had normal chain length.

Henry, A; Stacpoole, P W; Allen, C M



Primary cutaneous malignant melanoma of the breast  

PubMed Central

Cutaneous malignant melanoma of the breast can be divided into two categories: primary and metastatic lesions. Cutaneous malignant melanoma of the breast is a rare tumor, accounting for less than 5% of all malignant melanomas. Clinical features and diagnostic methods of primary cutaneous malignant melanoma of the breast are similar to those arising from other cutaneous areas. Treatment of choice is wide local excision with adequate resection margin according to tumor thickness. Sentinel lymph node biopsy should be performed because the presence of lymph node metastasis is the most important prognostic factor. There have been only limited reports involving primary cutaneous malignant melanoma of the breast. Thus, we report a case of primary cutaneous malignant melanoma in a 59-year-old woman with a review of the recent literature.

Kim, Seon Kwang; Kim, Young Wook; Park, Ho Sung; Jung, Sung Hoo



Infantile Myofibroma Eroding into the Frontal Bone: A Case Report and Review of Its Histopathologic Differential Diagnosis  

PubMed Central

Infantile myofibroma is a rare and benign tumour of children presenting in the head and neck region. Rendering a final diagnosis of infantile myofibroma can be challenging in the light of nonspecific clinical, radiological findings and its histopathological similarities with a number of neoplasms especially spindle cell tumours. In this paper we discuss a case of infantile myofibroma in a 2-month-old infant, enumerating the various differential entities that have to be eliminated in reaching its specific diagnosis and highlighting the importance of immunopositivity to vimentin and smooth muscle actin (SMA) in establishing its myofibroblastic differentiation.

Thennavan, Aatish; Narayanaswamy, Venkadasalapathi; Niazi, Thanvir Mohammed; Rao, Lakshmi; Radhakrishnan, Raghu



Imaging probe for tumor malignancy  

NASA Astrophysics Data System (ADS)

Solid tumors possess unique microenvironments that are exposed to chronic hypoxic conditions ("tumor hypoxia"). Although more than half a century has passed since it was suggested that tumor hypoxia correlated with poor treatment outcomes and contributed to cancer recurrence, a fundamental solution to this problem has yet to be found. Hypoxia-inducible factor (HIF-1) is the main transcription factor that regulates the cellular response to hypoxia. It induces various genes whose functions are strongly associated with malignant alteration of the entire tumor. The cellular changes induced by HIF-1 are extremely important targets of cancer therapy, particularly in therapy against refractory cancers. Imaging of the HIF-1-active microenvironment is therefore important for cancer therapy. To image HIF-1activity in vivo, we developed a PTD-ODD fusion protein, POHA, which was uniquely labeled with near-infrared fluorescent dye at the C-terminal. POHA has two functional domains: protein transduction domain (PTD) and VHL-mediated protein destruction motif in oxygen-dependent degradation (ODD) domain of the alpha subunit of HIF-1 (HIF-1?). It can therefore be delivered to the entire body and remain stabilized in the HIF-1-active cells. When it was intravenously injected into tumor-bearing mice, a tumor-specific fluorescence signal was detected in the tumor 6 h after the injection. These results suggest that POHA can be used an imaging probe for tumor malignancy.

Tanaka, Shotaro; Kizaka-Kondoh, Shinae; Hiraoka, Hasahiro



Malignant small round cell tumors  

PubMed Central

Malignant small round cell tumors are characterised by small, round, relatively undifferentiated cells. They generally include Ewing's sarcoma, peripheral neuroectodermal tumor, rhabdomyosarcoma, synovial sarcoma, non-Hodgkin's lymphoma, retinoblastoma, neuroblastoma, hepatoblastoma, and nephroblastoma or Wilms’ tumor. Other differential diagnoses of small round cell tumors include small cell osteogenic sarcoma, undifferentiated hepatoblastoma, granulocytic sarcoma, and intraabdominal desmoplastic small round cell tumor. Differential diagnosis of small round cell tumors is particularly difficult due to their undifferentiated or primitive character. Tumors that show good differentiation are generally easy to diagnose, but when a tumor is poorly differentiated, identification of the diagnostic, morphological features is difficult and therefore, no definitive diagnosis may be possible. As seen in several study reports, fine needle aspiration cytology (FNAC) has become an important modality of diagnosis for these tumors. The technique yields adequate numbers of dissociated, viable cells, making it ideally suitable for ancillary techniques. Typically, a multimodal approach is employed and the principal ancillary techniques that have been found to be useful in classification are immunohistochemistry and immunophenotyping by flow cytometry, reverse transcriptase polymerase chain reaction (RT-PCR), fluorescence in situ hybridization (FISH), and electron microscopy. However, the recent characterization of chromosomal breakpoints and the corresponding genes involved in malignant small round cell tumors means that it is possible to use molecular genetic approaches for detection.

Rajwanshi, Arvind; Srinivas, Radhika; Upasana, Gautam



Genome sequencing of lymphoid malignancies.  


Our understanding of the pathogenesis of lymphoid malignancies has been transformed by next-generation sequencing. The studies in this review have used whole-genome, exome, and transcriptome sequencing to identify recurring structural genetic alterations and sequence mutations that target key cellular pathways in acute lymphoblastic leukemia (ALL) and the lymphomas. Although each tumor type is characterized by a unique genomic landscape, several cellular pathways are mutated in multiple tumor types-transcriptional regulation of differentiation, antigen receptor signaling, tyrosine kinase and Ras signaling, and epigenetic modifications-and individual genes are mutated in multiple tumors, notably TCF3, NOTCH1, MYD88, and BRAF. In addition to providing fundamental insights into tumorigenesis, these studies have also identified potential new markers for diagnosis, risk stratification, and therapeutic intervention. Several genetic alterations are intuitively "druggable" with existing agents, for example, kinase-activating lesions in high-risk B-cell ALL, NOTCH1 in both leukemia and lymphoma, and BRAF in hairy cell leukemia. Future sequencing efforts are required to comprehensively define the genetic basis of all lymphoid malignancies, examine the relative roles of germline and somatic variation, dissect the genetic basis of clonal heterogeneity, and chart a course for clinical sequencing and translation to improved therapeutic outcomes. PMID:24041576

Mullighan, Charles G



Management of malignant bowel obstruction.  


Malignant bowel obstruction (MBO) is a common and distressing outcome particularly in patients with bowel or gynaecological cancer. Radiological imaging, particularly with CT, is critical in determining the cause of obstruction and possible therapeutic interventions. Although surgery should be the primary treatment for selected patients with MBO, it should not be undertaken routinely in patients known to have poor prognostic criteria for surgical intervention such as intra-abdominal carcinomatosis, poor performance status and massive ascites. A number of treatment options are now available for patients unfit for surgery. Nasogastric drainage should generally only be a temporary measure. Self-expanding metallic stents are an option in malignant obstruction of the gastric outlet, proximal small bowel and colon. Medical measures such as analgesics according to the W.H.O. guidelines provide adequate pain relief. Vomiting may be controlled using anti-secretory drugs or/and anti-emetics. Somatostatin analogues (e.g. octreotide) reduce gastrointestinal secretions very rapidly and have a particularly important role in patients with high obstruction if hyoscine butylbromide fails. A collaborative approach by surgeons and the oncologist and/or palliative care physician as well as an honest discourse between physicians and patients can offer an individualised and appropriate symptom management plan. PMID:18359221

Ripamonti, Carla Ida; Easson, Alexandra M; Gerdes, Hans



Oncolytic Virotherapy for Hematological Malignancies  

PubMed Central

Hematological malignancies such as leukemias, lymphomas, multiple myeloma (MM), and the myelodysplastic syndromes (MDSs) primarily affect adults and are difficult to treat. For high-risk disease, hematopoietic stem cell transplant (HCT) can be used. However, in the setting of autologous HCT, relapse due to contamination of the autograft with cancer cells remains a major challenge. Ex vivo manipulations of the autograft to purge cancer cells using chemotherapies and toxins have been attempted. Because these past strategies lack specificity for malignant cells and often impair the normal hematopoietic stem and progenitor cells, prior efforts to ex vivo purge autografts have resulted in prolonged cytopenias and graft failure. The ideal ex vivo purging agent would selectively target the contaminating cancer cells while spare normal stem and progenitor cells and would be applied quickly without toxicities to the recipient. One agent which meets these criteria is oncolytic viruses. This paper details experimental progress with reovirus, myxoma virus, measles virus, vesicular stomatitis virus, coxsackievirus, and vaccinia virus as well as requirements for translation of these results to the clinic.

Bais, Swarna; Bartee, Eric; Rahman, Masmudur M.; McFadden, Grant; Cogle, Christopher R.



Retinal changes in malignant hypertension.  

PubMed Central

To assess the diagnostic and prognostic importance of papilloedema in malignant hypertension a two part study was undertaken. Four observers reviewed 56 photographs of fundi from patients with grade 3 or 4 hypertensive retinopathy. Complete agreement on the presence or absence of haemorrhages was recorded in 52 cases and on exudates in 53 cases. Opinion on papilloedema, however, was divided, all four observers agreeing in only 34 cases. In the second part of the study survival in 139 consecutive hypertensive patients with bilateral retinal haemorrhages and exudates was examined by life tables. Ten year survival was 46% in patients with bilateral haemorrhages and exudates alone (n = 43) and 48% when papilloedema was also present (n = 96). Multivariate analysis confirmed that papilloedema was not related to survival. These results suggest that papilloedema is an unreliable physical sign and does not adversely influence prognosis in hypertensive patients who already have bilateral retinal haemorrhages and exudates when effective treatment is available. Papilloedema should no longer be regarded as a necessary feature of malignant hypertension.

McGregor, E; Isles, C G; Jay, J L; Lever, A F; Murray, G D



Advances in diffuse malignant peritoneal mesothelioma  

Microsoft Academic Search

Malignant mesothelioma is a highly aggressive neoplasm. The incidence of malignant mesothelioma is increasing worldwide. Diffuse\\u000a malignant peritoneal mesothelioma (DMPM) represents one-fourth of all mesotheliomas. Association of asbestos exposure with\\u000a DMPM has been observed, especially in males. A great majority of patients present with abdominal pain and distension, caused\\u000a by accumulation of tumors and ascitic fluid. In the past, DMPM

Tristan D. Yan; Raffit Hassan; Laura Welch; Paul H. Sugarbaker



Delayed Onset Malignant Hyperthermia after Sevoflurane  

PubMed Central

Malignant hyperthermia is a hypermetabolic response to inhalation agents (such as halothane, sevoflurane, and desflurane), succinylcholine, vigorous exercise, and heat. Reactions develop more frequently in males than females (2?:?1). The classical signs of malignant hyperthermia are hyperthermia, tachycardia, tachypnea, increased carbon dioxide production, increased oxygen consumption, acidosis, muscle rigidity and rhabdomyolysis. In this case report, we present a case of delayed onset malignant hyperthermia-like reaction after the second exposure to sevoflurane.

Turhan, K. Sanem Cakar; Baytas, Volkan; Batislam, Yesim; Ozatamer, Oya



Infantile Pompe disease on ERT: update on clinical presentation, musculoskeletal management, and exercise considerations.  


Enzyme replacement therapy (ERT) with alglucosidase alpha, approved by the FDA in 2006, has expanded possibilities for individuals with Pompe disease (glycogen storage disease type II, GSDII, or acid maltase deficiency). Children with infantile Pompe disease are surviving beyond infancy, some achieving independent walking and functional levels never before possible. Individuals with late-onset Pompe disease are experiencing motor and respiratory improvement and/or stabilization with slower progression of impairments. A new phenotype is emerging for those with infantile Pompe disease treated with ERT. This new phenotype appears to be distinct from the late-onset phenotype rather than a shift from infantile to late-onset phenotype that might be expected from a simple diminution of symptoms with ERT. Questions arise regarding the etiology of the distinct distribution of weakness in this new phenotype, with increasing questions regarding exercise and musculoskeletal management. Answers require an increased understanding of the muscle pathology in Pompe disease, how that muscle pathology may be impacted by ERT, and the potential impact of, and need for, other clinical interventions. This article reviews the current state of knowledge regarding the pathology of muscle involvement in Pompe disease and the potential change in muscle pathology with ERT; the newly emerging musculoskeletal and gross motor phenotype of infantile Pompe disease treated with ERT; updated recommendations regarding musculoskeletal management in Pompe disease, particularly in children now surviving longer with residual weakness impacting development and integrity of the musculoskeletal system; and the potential impact and role of exercise in infantile Pompe survivors treated with ERT. PMID:22252989

Case, Laura E; Beckemeyer, Alexandra A; Kishnani, Priya S



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

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.

Williams, R.; McKay, T.; Mitchison, H.; Gardiner, M. (Univ. College of London Medical School (United Kingdom)); Vesa, J.; Jaervelae, I.; Hellsten, E.; Peltonen, L.; Thompson, A.; Callen, D.; Sutherland, G.; Luna-Battadano, D.; Stallings, R.



[Malignant lymphoma of the skin].  


Extranodal non-Hodgkin lymphomas preferentially involve the skin. Among them, 65% are T-cell lymphomas, 25% B-cell lymphomas and about 10% rare variants or nonclassifiable lymphomas. Mycosis fungoides is the most common form of low-grade malignant peripheral cutaneous T-cell lymphoma (CTCL): Lymphomas originating from follicular center cells are the most common types of cutaneous B-cell lymphomas (CBCL). Only 15 to 25% of cutaneous lymphomas show extracutaneous manifestations at time of diagnosis. The prognosis is relatively good, since the average survival time from diagnosis is 12 to 14 years. For making the diagnosis, clinical, histo- and cytomorphological parameters often have to be supplemented by phenotypic, genotypic and molecular biologic techniques in order to establish the correct diagnosis. An important problem still is the early diagnosis and early evaluation of prognostic parameters in CTCL. The therapeutic approach is control of the disease according to stage and prognostic parameters. PMID:8171405

Burg, G; Dommann, S; Dummer, R



Malignant mesothelioma: development to therapy.  


Malignant mesothelioma (MM) is an aggressive cancer of the mesothelium caused by asbestos. Asbestos use has been reduced but not completely stopped. In addition, natural or man-made disasters will continue to dislodge asbestos from old buildings into the atmosphere and as long as respirable asbestos is available, MM will continue to be a threat. Due to the long latency period of MM development, it would still take decades to eradicate this disease if asbestos was completely removed from our lives today. Therefore, there is a need for researchers and clinicians to work together to understand this deadly disease and find a solution for early diagnosis and treatment. This article focuses on developmental mechanisms as well as current therapies available for MM. PMID:23959774

Thompson, Joyce K; Westbom, Catherine M; Shukla, Arti



Medicinal arsenic and internal malignancies.  

PubMed Central

A mortality analysis has been carried out on a cohort of patients given Fowler's solution (potassium arsenite) for periods ranging from 2 weeks to 12 years between 1945 and 1969. An excess of fatal and non-fatal skin cancer was apparent, but there was no overall excess mortality from cancer. Further analyses by site of cancer, dose level, and time from first exposure are also presented. A subset of patients were examined in 1969-70 for the presence of arsenical keratoses, hyperpigmentation and skin cancer. About half the patients had one or more of these signs. Although the cancer mortality of this entire subgroup was similar to the expected value, all the cancer deaths occurred in patients with prior signs of arsenicism. These data suggest that while any excess of internal malignancy due to the use of Fowler's solution is small or non-existent, there may be a susceptible subgroup which can be identified from dermatological manifestations.

Cuzick, J.; Evans, S.; Gillman, M.; Price Evans, D. A.



Irreversible Electroporation of Hepatic Malignancy  

PubMed Central

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.

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



Immunotherapy of malignancies: current status.  


The results of various in vitro analyses indicate there is an active immune response against antigens associated with human malignancies. This immune response apparently can be augmented by nonspecific immunologic stimulates such as BCG. These agents are effective for destroying tumor when injected locally into intracutaneous disease but are not as effective for subcutaneous disease. Preliminary clinical trials indicated that immune stimulants are effective when administered systemically. The effect is only minimal for diseminated disease, but the therapeutic benefit is clearly augmented for patients with a minimal residual tumor burden, such as those patients with metastases to regional lymph nodes. Thus immunotherapy is a systemically active mode of therapy. Its toxicity is minimal, and it appears to be effective in a wide spectrum of the disease. However, immunotherapy is not effective for a large residual tumor burden; consequently it must be used in combination with other modes of treatment such as irradiation therapy or chemotherapy. Early experiences with BCG immunotherapy for malignant melanoma and C. parvum for oat cell carcinoma are encouraging. It is remarkable that a nonspecific immunologic stimulant does, in fact, have this effect. Immunotherapy experiments in animals suggest that in order to achieve maximal benefit. BCG must have close contact with tumor cells or must be combined with a tumor-associated antigen. If these principles are true for man, it would seem that improvements for nonspecific immunotherapy in human neoplasms would be further augmented if a tumor-related antigen could be extracted from human tumours and combined with a nonspecific immunologic stimulant. PMID:178234

Eilber, F R; Holmes, E C; Morton, D L; Ramming, K P; Sparks, F C



Intussusception Presenting with Malignant Hypertension and Lethargy  

PubMed Central

The most common cause of malignant hypertension in children is renal or renovascular pathology. The combination with lethargy suggests a diagnosis of hypertensive crisis with hypertensive encephalopathy. Here, we present a case of severe hypertension with lethargy as the sole presenting symptoms of ileocecal intussusception. Both normalized following surgical repositioning. We conclude that malignant hypertension and lethargy can be presenting symptoms of intussusception.

de Vries, Andra; Ashtiani, Nilou; Ahmadi, Nazanin; Bakx, Roel; de Vaate, Annelies Walrave-bij; Bokenkamp, Arend



Malignancy in Children with Trisomy 21  

Microsoft Academic Search

Patients with Down syndrome (DS) display a unique spectrum of malignancies, with a 10- to 20-fold higher riskofacuteleukemias,andamarkedlylowerincidence of solid tumors. This review discusses the current un- derstanding of the basis for this distinctive pattern of cancerincidenceandtheclinicalandbiologicfeaturesof the malignant disorders most frequent in DS individ- uals: transient myeloproliferative disease, acute megakaryoblastic leukemia, and acute lymphoblastic leukemia. We also review distinctive



Malignant Peritoneal Mesothelioma Mimicking Ischemic Colitis  

Microsoft Academic Search

The prognosis of malignant peritoneal mesothelioma is extremely poor with a mean survival time of 12 months. The initial symptoms are poor and atypical. Because of its rare entity and little knowledge of its treatments, there are few reports of long-term survival. We encountered a very unique case with strong impression on radiological findings of malignant peritoneal methothelioma. We had

Yuusuke Mitsuka; Shintaro Yamazaki; Taiki Miyakuni; Atsuko Iwama; Tomoya Funada; Yoshifumi Watanabe; Teruo Kaiga; Shunji Okada; Mitsugu Kochi; Tadatoshi Takayama



Natural history of cutaneous malignant melanoma  

Microsoft Academic Search

The rising incidence of cutaneous malignant melanoma with the consequent increase in mortality from melanoma has intensified efforts to understand the factors that initiate the malignant transformation of melanocytes and to define those tumor-host interactions that play a relevant role in the clinical course of this disease. Increased exposure to solar radiation has been proposed as an explanation for the

Henry A. Briele; T. K. Das Gupta



Malignant melanoma with probable smooth muscle differentiation.  


Malignant melanomas occasionally exhibit various divergent differentiation types. Of these, smooth muscle differentiation is extremely rare; only 1 case has been reported in the literature until recently. We report an extremely rare case of malignant melanoma with smooth muscle differentiation, which appeared as an amelanotic reddish nodule on the left toe. PMID:24575006

Morimoto, Aya; Asai, Jun; Wakabayashi, Yusuke; Komori, Satoshi; Hanada, Keiji; Takenaka, Hideya; Konishi, Eiichi; Katoh, Norito



Immunotoxin therapy for primary malignant brain tumors  

Microsoft Academic Search

The prognosis of malignant brain tumors is poor in spite of aggressive treatment. Immunotoxin therapy is a novel approach for the treatment of tumors. Targeted fusion toxins, chimeric protein consisting of the cytotoxic domain of the natural toxin and carrier ligands such as a growth factor or an antibody, have been introduced in the treatment of malignant central nervous system

Ki-Uk Kim; Daniel A. Vallera; Hsiao-Tzu Ni; Kwan H. Cho; Stephen R. Spellman; Walter C. Low; Walter A. Hall



Malignant ameloblastoma: Classification, diagnostic, and therapeutic challenges  

Microsoft Academic Search

Ameloblastoma is a benign odontogenic neoplasm of the mandible and maxilla that rarely exhibits malignant behavior. We report the case of an aggressive malignant ameloblastoma of the mandible that presented with an unusual multiphasic, histologic pattern. Initial fine needle aspiration and radiographic findings showed features consistent with a benign, fibro-osseous lesion. However, aggressive growth and the association of enlarged submandibular

Andrew Verneuil; Philip Sapp; Catherine Huang; Elliot Abemayor



Malignant Triton Tumor (MTT) of the neck  

Microsoft Academic Search

Malignant Triton Tumor (MTT) is a rare, malignant periphere nerve sheath tumor with rhabdomyoblastic differentiation. One third of described MTT's were located at the head and neck region. One third of these are associated with neurofibromatosis type 1. MTT most often appears in the third decade.MTT's are very aggressive tumors with early metastases and the overall survival is poor (26%).

Kristine Bjørndal Sørensen; Christian Godballe; Annelise Krogdahl



Cerebellar atrophy without cerebellar cortex hyperintensity in infantile neuroaxonal dystrophy (INAD) due to PLA2G6 mutation  

Microsoft Academic Search

Infantile neuroaxonal dystrophy (INAD) is a rare neurodegenerative disorder characterized by infantile onset and rapid progression of psychomotor regression and hypotonia evolving into spasticity. The neuroradiologic hallmark of the disease is represented by cerebellar atrophy and signal hyperintensity in the cerebellar cortex on MR T2-weighted images. We report a 2-year-old boy with psychomotor regression and hypotonia carrying a homozygous 5?

Roberta Biancheri; Andrea Rossi; Giannina Alpigiani; Mirella Filocamo; Carlo Gandolfo; Renata Lorini; Carlo Minetti



Management of malignant hyperthermia: diagnosis and treatment  

PubMed Central

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.

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



Genetics Home Reference: Malignant migrating partial seizures of infancy  


... disorder catalog Conditions > Malignant migrating partial seizures of infancy On this page: Description Genetic changes Inheritance Diagnosis ... 2014 What is malignant migrating partial seizures of infancy? Malignant migrating partial seizures of infancy (MMPSI) is ...


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

PubMed Central

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.

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



Clinical profile of vigabatrin as monotherapy for treatment of infantile spasms  

PubMed Central

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.

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



IgE-mediated cow milk allergy and infantile colic: diagnostic and management challenges.  


Cow milk allergy (CMA) is a common problem affecting 2-3% of children and is the most prevalent food allergy in infancy. Infantile colic is also a common problem in the first year of life. A frequent practice among physicians is to recommend a dairy-free diet to breast-feeding mothers and infants in cases of infantile colic. However, recent studies suggest that late introduction of potentially allergenic foods may increase the risk of developing a life-threatening food allergy. We describe two infants managed with dairy-free diet to control symptoms of colic in whom CMA developed. It is possible that unnecessary cow milk restriction may have contributed to the development of food allergy in these infants. PMID:23391944

Al Dhaheri, Watfa; Diksic, Dubravka; Ben-Shoshan, Moshe



Treatment of complex infantile haemangioma in a resource-poor setting.  


Infantile haemangiomas affect approximately 5% of the population and usually do not require treatment. However, complex cutaneous haemangiomas can cause disabling disfigurement, while haemangiomas in the brain, airway or gastrointestinal tract can cause life-threatening complications. Although children with infantile haemangiomas are often first brought to general practitioners and paediatricians by parents for care, they are thought of as a surgical problem and usually referred to specialty care. We present a case of an infant from a resource-poor setting in rural Indonesia with disfiguring facial haemangiomas, as well as a probable airway haemangioma causing stridor at rest. The infant was treated with oral propranolol with marked involution of the cutaneous haemangioma, resolution of stridor and increase in weight. PMID:25053694

Natawidjaja, Ronald; Wang, Ewen



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


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

Olivetti, Pedro R; Noebels, Jeffrey L



Transcriptional response to GAA deficiency (Pompe disease) in infantile-onset patients.  


Pompe disease is a genetic disorder resulting from a deficiency of lysosomal acid alpha-glucosidase (GAA) that manifests as a clinical spectrum with regard to symptom severity and rate of progression. In this study, we used microarrays to examine gene expression from the muscle of two cohorts of infantile-onset Pompe patients to identify transcriptional differences that may contribute to the disease phenotype. We found strong similarities among the gene expression profiles generated from biceps and quadriceps, and identified a number of signaling pathways altered in both cohorts. We also found that infantile-onset Pompe patient muscle had a gene expression pattern characteristic of immature or regenerating muscle, and exhibited many transcriptional markers of inflammation, despite having few overt signs of inflammatory infiltrate. Further, we identified genes exhibiting correlation between expression at baseline and response to therapy. This combined dataset can serve as a foundation for biological discovery and biomarker development to improve the treatment of Pompe disease. PMID:22658377

Palermo, A T; Palmer, R E; So, K S; Oba-Shinjo, S M; Zhang, M; Richards, B; Madhiwalla, S T; Finn, P F; Hasegawa, A; Ciociola, K M; Pescatori, M; McVie-Wylie, A J; Mattaliano, R J; Madden, S L; Marie, S K N; Klinger, K W; Pomponio, R J



Prenatal and postnatal risk factors for infantile pneumonia in a representative birth cohort.  


Pneumonia is an important cause of mortality and morbidity in infants. However, information of risk factors for pneumonia in children aged <6 months is limited. This study aimed to evaluate the risk factors and their contribution to infantile pneumonia in a large population-based survey. Of 24,200 randomly sampled main caregivers invited, 21,248 (87.8%) participated in this study. A structured questionnaire was used to interview the main caregivers. Information regarding whether hospitalization was required, family environment, and medical history were obtained. The prevalence of pneumonia was 0.62% in our study cohort. Multivariate logistic regression analysis showed that preterm birth, congenital cardiopulmonary disease, antibiotic use during pregnancy, maternal overweight, daily prenatal exposure to environmental tobacco smoke, maternal smoking during pregnancy, and visible mould on walls at home are risk factors associated with infantile pneumonia. Further study is warranted to investigate the causality and mechanisms of these novel factors. PMID:21920066

Chen, C H; Wen, H J; Chen, P C; Lin, S J; Chiang, T L; Hsieh, I C; Guo, Y L



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

SciTech Connect

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.

Smirnova, Anna S. [Immunogenetics Division, Pediatrics Department, Universidade Federal de Sao Paulo (UNIFESP-EPM), Sao Paulo (Brazil); Morgun, Andrey [Immunogenetics Division, Pediatrics Department, Universidade Federal de Sao Paulo (UNIFESP-EPM), Sao Paulo (Brazil)]. E-mail:; Shulzhenko, Natalia [Immunogenetics Division, Pediatrics Department, Universidade Federal de Sao Paulo (UNIFESP-EPM), Sao Paulo (Brazil); Silva, Ismael D.C.G. [Gynecology Department, Universidade Federal de Sao Paulo (UNIFESP-EPM), Sao Paulo (Brazil); Gerbase-DeLima, Maria [Immunogenetics Division, Pediatrics Department, Universidade Federal de Sao Paulo (UNIFESP-EPM), Sao Paulo (Brazil)



Malignant hyperthermia and myotonic disorders.  


Advances in physiology and molecular genetics have promoted greater understanding of the various clinical manifestations of muscle disorders. For example, myotonia or profound weakness may be observed in sodium channel disease (e.g., paramyotonia congenita or hyperkalemic periodic paralysis), depending on the specific channel defect or with slight changes in membrane potential. Observed effects of anesthetic techniques have been essential to elucidating the primary muscular nature of myotonia. Commonly used anesthetic medications have potentially lethal (e.g., MH) or serious (e.g., myotonic dystrophy) adverse effects. Conversely, lidocaine or propofol may have therapeutic benefit for patients with skeletal muscle sodium channel disorders. Additional investigation is required to improve our understanding of how age, gender, or other factors determine the phenotypic expression of malignant hyperthermia. Future research holds the promise for more accurate pre-anesthetic identification of persons with heritable myopathies, especially those who are asymptomatic. Enhanced awareness of multiple organ system involvement in myotonic dystrophy is essential for planning perioperative care. Patients with periodic paralysis require that we know factors that incite or inhibit the development of their attacks. Advances in bench research and detailed clinical studies will further improve our ability to provide optimal care for patients with muscle disorders. PMID:12298310

Rosenbaum, Harvey K; Miller, Jordan D



Malignant melanoma and bone resorption  

PubMed Central

The cellular and humoral mechanisms accounting for osteolysis in skeletal metastases of malignant melanoma are uncertain. Osteoclasts, the specialised multinucleated cells that carry out bone resorption, are derived from monocyte/macrophage precursors. We isolated tumour-associated macrophages (TAMs) from metastatic (lymph node/skin) melanomas and cultured them in the presence and absence of osteoclastogenic cytokines and growth factors. The effect of tumour-derived fibroblasts and melanoma cells on osteoclast formation and resorption was also analysed. Melanoma TAMs (CD14+/CD51?) differentiated into osteoclasts (CD14?/CD51+) in the presence of receptor activator for nuclear factor ?B ligand (RANKL) and macrophage-colony stimulating factor. Tumour-associated macrophage-osteoclast differentiation also occurred via a RANKL-independent pathway when TAMs were cultured with tumour necrosis factor-? and interleukin (IL)-1?. RT–PCR showed that fibroblasts isolated from metastatic melanomas expressed RANKL messenger RNA and the conditioned medium of cultured melanoma fibroblasts was found to be capable of inducing osteoclast formation in the absence of RANKL; this effect was inhibited by the addition of osteoprotegerin (OPG). We also found that cultured human SK-Mel-29 melanoma cells produce a soluble factor that induces osteoclast differentiation; this effect was not inhibited by OPG. Our findings indicate that TAMs in metastatic melanomas can differentiate into osteoclasts and that melanoma fibroblasts and melanoma tumour cells can induce osteoclast formation by RANKL-dependent and RANKL-independent mechanisms, respectively.

Lau, Y S; Sabokbar, A; Giele, H; Cerundolo, V; Hofstetter, W; Athanasou, N A



Improved radioimmunotherapy of hematologic malignancies  

SciTech Connect

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.

Press, O.W.



Site distribution of malignant melanoma.  

PubMed Central

In a continuous series of 300 patients with cutaneous malignant melanoma the site of the primary lesion was recorded, and incidence rates per unit area of skin were calculated. These rates were high for the face, back and upper arm and low for the abdomen, buttocks, forearm and hand for both sexes. Rates for the leg were high for the women but low for the men. Tumours on the back were evenly distributed among the men but occurred less frequently on the lower back among the women. In general, sites that were usually covered by clothing had lower rates than those usually exposed, with the exception of the forearms and hands. No relation was seen between tumour site and age, sex, depth of invasion or month of diagnosis. Superficial spreading and nodular melanomas did not differ in their site distribution. Incidence rates per unit area at different ages were estimated for sites grouped by their degree of usual exposure: while the rates for unexposed sites were low, those for usually or intermittently exposed sites were higher and similar to each other.

Elwood, J. M.; Gallagher, R. P.



Clostridium difficile in haematological malignancy.  

PubMed Central

Twenty patients with haematological malignancies who developed Clostridium difficile bowel infection or colonisation are described. All isolates of C difficile were toxigenic in vitro and faecal cytotoxin (toxin B) was detected in 20/26 episodes. Ten of 20 episodes with detectable faecal cytotoxin were associated with typical antibiotic associated diarrhoea. In the other 10 episodes (nine patients), there was a severe unusual illness which was associated with detection of C difficile. The unusual features of the illness were pronounced jaundice (total bilirubin greater than or equal to 44 mumol/l), abdominal pain and distension, and initial constipation followed either by diarrhoea or by large bowel stasis. Four of these patients died within seven days. Bacteraemia was often a presenting feature in neutropenic patients subsequently shown to have C difficile. This was not the case in non-neutropenic patients. Bacteraemia was commonly polymicrobial and in two cases C difficile was isolated from blood culture. The clinical implications of recognition of this atypical C difficile associated syndrome are discussed.

Rampling, A; Warren, R E; Bevan, P C; Hoggarth, C E; Swirsky, D; Hayhoe, F G



Malignant ascites: pathophysiology and treatment.  


Malignant ascites (MA) accompanies a variety of abdominal and extra-abdominal tumors. It is a primary cause of morbidity and raises several treatment challenges. MA has several symptoms, producing a significant reduction in the patient's quality of life: loss of proteins and electrolyte disorders cause diffuse oedema, while the accumulation of abdominal fluid facilitates sepsis. Treatment options include a multitude of different procedures with limited efficacy and some degree of risk. A Pubmed, Medline, Embase, and Cochrane Library review of medical, interventional and surgical treatments of MA has been performed. Medical therapy, primarily paracentesis and diuretics, are first-line treatments in managing MA. Paracentesis is widely adopted but it is associated with significant patient discomfort and several risks. Diuretic therapy is effective at the very beginning of the disease but efficacy declines with tumor progression. Intraperitoneal chemotherapy, targeted therapy, immunotherapy and radioisotopes are promising medical options but their clinical application is not yet completely elucidated, and further investigations and trials are necessary. Peritoneal-venous shunts are rarely used due to high rates of early mortality and complications. Laparoscopy and hyperthermic intraperitoneal chemotherapy (HIPEC) have been proposed as palliative therapy. Literature on the use of laparoscopic HIPEC in MA includes only reports with small numbers of patients, all showing successful control of ascites. To date, none of the different options has been subjected to evidence-based clinical trials and there are no accepted guidelines for the management of MA. PMID:22460778

Cavazzoni, Emanuel; Bugiantella, Walter; Graziosi, Luigina; Franceschini, Maria Silvia; Donini, Annibale



The presence of two different infantile Tay-Sachs disease mutations in a Cajun population  

Microsoft Academic Search

A study was undertaken to characterize the mutation(s) responsible for Tay-Sachs disease (TSD) in a Cajun population in southwest Louisiana and to identify the origins of these mutations. Eleven of 12 infantile TSD alleles examined in six families had the [beta]-hexosaminidase A (Hex A) [alpha]-subunit exon 11 insertion mutation that is present in approximately 70% of Ashkenazi Jewish TSD heterozygotes.

G. A. McDowell; M. G. Blitzer; E. H. Mules; P. Fabacher; E. Shapira




Microsoft Academic Search

RESUMO: Abordamos, neste artigo, a questão dos modos de subjetivação (re)produzidos no filme infantil A Pequena Sereia, a partir de uma análise da figura do feminino. Ao contrário do que se poderia supor, a enunciação fílmica não prima somente pelo entretenimento; os filmes infantis trazem grandes discussões de cunho político-ideológico neles presentes de modo indireto. Com efeito, por tratar-se de

Érica Daniela de Araújo; Isabella Freitas Leal; Carmen Agustini


Stretched and Sheared Microcatheter Retained after Onyx Embolization of Infantile Myofibromatosis  

PubMed Central

Summary We describe a rare neurointerventional complication, namely a stretched and sheared microcatheter, extending 52 cm from its point of retention within an Onyx cast in an infant patient’s neck mass, to the groin. The tumor was an unusual manifestation of infantile myofibromatosis and prior attempts at resection had proven impossible due to bleeding. Recommendations regarding microcatheter selection, diagnostic workup, and management of the ensuing complication are given.

Puri, A.S.; Rahbar, R.; Dearden, J.; Graham, R.J.; Lillehei, C.; Orbach, D.B.



Infantile Overnutrition in the First Year of Life: A Field Study in Dudley, Worcestershire  

Microsoft Academic Search

A survey of feeding patterns and nutrient intake in relation to the growth of 300 normal infants up to 1 year of age in Dudley, Worcestershire, highlights a problem of overnutrition in the group; 50 (16·7%) were found to be suffering from infantile obesity and a further 83 (27·7%) were overweight.During the first three months of life the daily energy

A. Shukla; H. A. Forsyth; Charlotte M. Anderson; S. M. Marwah



Genetic complementation in somatic cell hybrids of four variants of infantile G M2 gangliosidosis  

Microsoft Academic Search

Summary  Cell hybridizations between fibroblasts of four variants (B, O, AB, and B1) of infantile GM2 gangliosidosis were performed. Cocultivated as well as hybrid cells were analyzed for their capability to degrade exogenously\\u000a added [3H]-GM2. Hybridization of variant AB fibroblasts with fibroblasts of variant O, variant B, or variant B1 resulted in an enhanced\\u000a rate of GM2 hydrolysis, showing intergenic complementation.

S. Sonderfeld; S. Brendler; K. Sandhoff; H. Galjaard; A. T. Hoogeveen



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

Microsoft Academic Search

Psoas muscle spasticity is hypothesised as a rare cause of low back pain in patients with infantile cerebral palsy. The authors\\u000a describe a new manoeuvre for the study of psoas tenderness and ultrasound (US)-guided transabdominal botulinum toxin injection\\u000a technique. A possible causal relationship between psoas tension and low back pain was found incidentally in two examined cases.\\u000a In subsequent patients,

G. Marrè-Brunenghi; R. Camoriano; M. Valle; S. Boero



Acupuncture for infantile colic: A blinding-validated, randomized controlled multicentre trial in general practice  

PubMed Central

Abstract Objective Infantile colic is a painful condition in the first months of infancy. Acupuncture is used in Scandinavia as a treatment for infantile colic. A randomized controlled trial was carried out with the aim of testing the hypothesis that acupuncture treatment has a clinically relevant effect for this condition. Design A prospective, blinding-validated, randomized controlled multicentre trial in general practice. Research assistants and parents were blinded. Setting 13 GPs’ offices in Southern Norway. Intervention Three days of bilateral needling of the acupuncture point ST36, with no treatment as control. Subjects 113 patients were recruited; 23 patients were excluded, and 90 randomized; 79 diaries and 84 interviews were analysed. Main outcome measures Difference in changes in crying time during the trial period between the intervention and control group. Results The blinding validation questions showed a random distribution with p = 0.41 and 0.60, indicating true blinding. We found no statistically significant difference in crying time reduction between acupuncture and control group at any of the measured intervals, nor in the main analysis of differences in changes over time (p = 0.26). There was a tendency in favour of the acupuncture group, with a non-significant total baseline-corrected mean of 13 minutes (95% CI –24 to + 51) difference in crying time between the groups. This was not considered clinically relevant, according to protocol. Conclusion This trial of acupuncture treatment for infantile colic showed no statistically significant or clinically relevant effect. With the current evidence, the authors suggest that acupuncture for infantile colic should be restricted to clinical trials.



Structural immaturity of the pylorus muscle in infantile hypertrophic pyloric stenosis  

Microsoft Academic Search

Recent reports indicate that extracellular matrix and cytoskeleton plasmalemmal elements are altered in infantile hypertrophic\\u000a pyloric stenosis (IHPS). Desmin is a cytoskeletal protein that is important for the organization and function of muscular\\u000a fibers. It has been found to be increased in the smooth muscle in chronic intestinal pseudo-obstruction and in skeletal muscle\\u000a in some forms of myopathies as well

N. Guarino; H. Shima; P. Puri



Multiple mitochondrial tRNAM Leu[UUR] mutations associated with infantile myopathy  

Microsoft Academic Search

We have identified a cluster of mitochondrial tRNALeu[UUR], mutations in a severe case of infantile myopathy. There were A to G transitions found at mtDNA positions 3259, 3261, 3266 and 3268. These point mutations change the anticodon arm and the anticodon UAA, normally found in tRNALeu[UUR], to UGA which is the one of the tRNAsSer[UCN]. This is the first anticodon

S. Zanssen; M. Molnar; J. M. Schröder; G. Buse



Mental and behavioural outcome of infantile epilepsy treated by vigabatrin in tuberous sclerosis patients.  


Vigabatrin (VGB) has demonstrated high efficacy in infantile spasms (IS) due to tuberous sclerosis. Our first objective was to evaluate the cognitive long term effect outcome of children whose refractory spasms definitely disappeared when VGB was given as an add on drug. Our second objective was to determine the response of generalized epilepsy (infantile spasms) compared to partial epilepsy on cognitive impairment. A non selected series of 13 children underwent psychometric and behavioural evaluation before VGB initiation at a mean of 3 years on VGB treatment. Eight of them could perform detailed neuropsychological tests at follow-up. Seven had infantile spasms (Group I), they all were spasm free before 2 years of age and five remained with rare partial seizures (mean age, 5.5 years). Six others had partial epilepsy without spasms (Group II) and five remained with rare seizures (mean age, 7.5 years). Patients of Group I experienced dramatic changes. Developmental quotient (DQ) significantly rose in six out of seven by ten to more than 45 points (P = 0.03) and autistic behaviour disappeared in five out of the six who presented with. The four tested children had normal verbal level after 5 years and could integrate at school but they remained with marked visuospatial disabilities. By contrast, patients of Group II remained with an unchanged DQ of about 60 so that both groups had similar DQ levels on follow-up. The cessation of spasms with VGB is therefore associated with significant improvement of cognition and behaviour in children with tuberous sclerosis. Controlling secondary generalization induced by infantile spasms seems to be a key factor for mental development. PMID:10642043

Jambaqué, I; Chiron, C; Dumas, C; Mumford, J; Dulac, O



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


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

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



SCN2A mutation is associated with infantile spasms and bitemporal glucose hypometabolism  

PubMed Central

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.

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



Primary aldosteronism and malignant adrenocortical neoplasia.  

PubMed Central

Our experience indicates that although adrenal carcinoma is not a common cause of primary aldosteronism, 4 to 5% of patients in a single large series may have a malignant adrenocortical tumor. The magnitude of the hypokalemia and the hyperaldosteronuria tends to be greater in patients with malignant tumors, but these patients cannot be clearly separated from those with benign tumors or hyperplasia on this basis. Patients who have malignant tumors may have no chemical evidence of adrenocortical dysfunction other than excessive aldosterone secretion. Finally, a good response to spironolactone for months does not exclude adrenal carcinoma as the cause of primary aldosteronism. Images Fig. 1

Salassa, T. M.; Weeks, R. E.; Northcutt, R. C.; Carney, J. A.



Infections as complications of neuroleptic malignant syndrome.  


Neuroleptic malignant syndrome is an uncommon but potentially fatal side effect of antipsychotic drug treatment. Several serious complications have been associated with neuroleptic malignant syndrome, such as acute renal failure, deep venous thrombosis, pulmonary embolism and aspiration pneumonia. Reports on infections other than aspiration pneumonia appear, from the literature, to be uncommon. Four cases of infection (three cases of upper respiratory tract infection and one case of urinary tract infection) which developed during the course of neuroleptic malignant syndrome are reported and pathophysiological mechanisms underlying their presentation are suggested. PMID:18609425

Bilanakis, Nikolaos; Peritogiannis, Vaios; Kalampokis, Georgios



Giant malignant cystic pheochromocytoma: a case report.  


Cystic malignant pheochromocytomas are uncommon. Differing from solid pheochromocytomas, which produce catecholamines and present adrenergic syndrome, cystic pheochromocytomas, may not produce these. Preoperative diagnosis may be difficult. Ct scan is useful for preoperative management. In this report, we describe a case of a giant malignant cystic pheochromocytoma in a young woman (17 years old) which presented as giant abdominal mass. The malignancy was confirmed by the presence of liver metastasis. Two years after curative resection, the patient is in good health with no recurrence. PMID:24293913

Soufi, Mehdi; Lahlou, Mohammed K; Benamr, Said; Massrouri, Rahal; Mdaghri, Jalil; Essadel, Abdelhamid; El Hamid, Mohammadine; Taghy, Ahmed; Settaf, Abdelatif; Chad, Bouziane



[Management results of primary intracranial malignant lymphoma].  


Nineteen cases of primary malignant lymphoma of the central nervous system were reported. The clinical characteristics, diagnostic procedure and therapeutic method, especially concerning chemotherapy, were analysed. The following conclusions were obtained: 1) histological classifications and surgical procedures were not factors involved in prognosis. 2) radiotherapy was regarded as an effective but a palliative treatment. 3) combined chemotherapy for systemic malignant lymphoma, such as VEMP, VEP, COPP, seemed to be of little use for intracranial malignant lymphoma. 4) intra-arterial administration of high-dose methotrexate, ACNU and intravenous administration of high-dose cytosine arabinoside can be expected to be a useful chemotherapeutic approach. PMID:2215864

Hayashi, A; Kyuma, Y; Kuwabara, T; Fujitsu, K; Shinonaga, M; Yamaguchi, K; Sekido, K; Chiba, Y; Yamashita, T; Oda, M



Paraneoplastic dermatological manifestation of gastrointestinal malignancies  

PubMed Central

Numerous dermatological disorders have been associated with underlining malignancies of the gastrointestinal (GI) tract. Such cutaneous manifestations might have an important diagnostic value if they are the sole expressions of otherwise asymptomatic carcinomas. The recognition of some typical paraneoplastic dermatologic disorders can lead to the prompt diagnosis of the underlying malignancy, timely administration of therapy, and ultimately, better prognosis. In this review we discuss the most common paraneoplastic dermatological syndromes from the perspective of the practicing gastroenterologist. We also outline a comprehensive practical approach for the evaluation for occult malignancy in patients presenting with cutaneous findings potentially associated with GI cancers.

Dourmishev, Lyubomir A; Draganov, Peter V



A new assay for fast, reliable CRIM status determination in infantile-onset Pompe disease.  


Pompe disease is caused by a deficiency of acid ?-glucosidase (GAA; EC,, and the infantile-onset form is rapidly fatal if left untreated. However, recombinant human GAA (rhGAA) enzyme replacement therapy (ERT) extends survival for infantile Pompe patients. Although cross-reactive immunologic material (CRIM)-negative patients, who lack detectable endogenous GAA, mount an immune response to rhGAA that renders the therapy ineffective, timely induction of immune tolerance in these patients may improve clinical outcomes. Previously, CRIM status has been determined by Western blot analysis in cultured skin fibroblasts, a process that can take a few weeks. We present a blood-based CRIM assay that can yield results within 48 to 72 h. Results from this assay have been confirmed by GAA Western blot analysis in fibroblasts or by GAA sequencing in a small number of Pompe disease patients. Rapid classification of CRIM status will assist in identifying the most effective treatment course and minimizing treatment delays in patients with infantile-onset Pompe disease. PMID:24044919

Wang, Zhaohui; Okamoto, Patricia; Keutzer, Joan



Infantile spasms as an adverse outcome of neonatal cortical sinovenous thrombosis.  


Cerebral sinovenous thrombosis is a rare but potentially serious condition often occurring in children with nonspecific presenting features. Much remains to be learned about the long-term outcome of infants with cerebral sinovenous thrombosis. We report a series of four patients taken from a prospective database of neonates with sinovenous thrombosis who subsequently developed infantile spasms, three with hypsarrythmia on electroencephalography and one with multiple independent spike foci. The first patient presented at 2 weeks of age with hypernatremia, dehydration, and seizures. He was found to have extensive thrombosis and hemorrhagic infarction of the right basal ganglia. The second patient presented at 5 weeks of life and was found to have sagittal sinus thrombosis with bilateral intracranial hemorrhage. The third patient presented with seizures on day 1 of life and was found to have venous thrombosis involving the torcular, extending into the sagittal sinus. The fourth patient presented at 3 weeks with lethargy and seizures. He was diagnosed with bacterial meningitis and also had extensive sinus thrombosis. All patients developed infantile spasms at ages 9, 7, 11, and 10 months, respectively. This is the first report in the English literature describing infantile spasms as a possible outcome of sinovenous thrombosis in early infancy. PMID:16566876

Soman, Teesta B; Moharir, Mahendranath; DeVeber, Gabrielle; Weiss, Shelly



Effects of propranolol and isoproterenol on infantile hemangioma endothelial cells in vitro  

PubMed Central

The aim of the present study was to investigate the effects of propranolol and isoproterenol on the growth curve of infantile hemangioma endothelial cells (IHECs) in vitro and determine the functions of the ?-adrenergic receptor in the pathogenesis of infantile hemangioma. IHECs were divided into three groups: The control group, the propranolol group (PG) and the isoproterenol group (IG). The PG and IG were administered with high, medium and low concentrations of the corresponding drugs. The cell growth in each group was determined using the MTT assay. A high propranolol concentration resulted in the inhibition of cell growth. By comparison, isoproterenol promoted cell growth. Within a specific time-frame (72–96 h), high drug concentrations (20 ?g/ml) elicited strong effects on the cells. At certain concentrations, propranolol inhibited cell growth once the proliferation stage of IHECs had been affected for a specific length of time, whereas isoproterenol yielded opposite results. The ?-adrenergic receptor elicits an important effect in the pathogenesis of infantile hemangioma.




Early retreatment of infantile esotropia: comparison of reoperation and botulinum toxin  

PubMed Central

AIM—To compare the efficacy of reoperation and botulinum toxin injection in treating infantile esotropes early after unsatisfactory surgical alignment.?METHODS—55 strabismic children who had been unsuccessfully operated for infantile esotropia were randomised to reoperation (28 patients) or botulinum toxin injection (27 patients). The motor outcomes (percentage of successful motor outcome and percentage change in deviation) were compared at 6 months, 1 year, and 3 years after retreatment, and the sensory outcomes (percentage with fusion ability and stereo perception) at the 3 year follow up visit.?RESULTS—The motor and sensory outcomes and the stability of motor results were similar in patients reoperated and treated with botulinum injection. At the 3 year visit 67.8% and 59.2% of children were, respectively, within 8 prism dioptres of orthotropia (p=0.72). The frequency of fusion ability was, respectively, 60.7% and 51.8% (p=0.71), and the frequency of stereo perception (?400 seconds of arc, Randot circles), 57.1% and 48.1% (p=0.70). The botulinum injection was more likely to be effective when carried out in the 6 months following initial surgery.?CONCLUSIONS—Botulinum injection is a rapid and less invasive alternative to reoperation in children who have been unsuccessfully treated with surgery to correct infantile esotropia.??

Tejedor, J.; Rodriguez, J.



Evidence by molecular profiling for a placental origin of infantile hemangioma  

PubMed Central

The origin of the pathogenic endothelial cells in common infantile hemangioma is unknown. We show here that the transcriptomes of human placenta and infantile hemangioma are sufficiently similar to suggest a placental origin for this tumor, expanding on recent immunophenotypical studies that have suggested this possibility [North, P. E., et al. (2001) Arch. Dermatol. 137, 559-570]. The transcriptomes of placenta, hemangioma, and eight normal and diseased tissues were compared by hierarchical and nonhierarchical clustering analysis of >7,800 genes. We found that the level of transcriptome similarity between placenta and hemangioma exceeded that of any other tissue compared and paralleled that observed between a given tissue and its derived tumor, such as normal and cancerous lung. The degree of similarity was even greater when a subset of endothelial cell-specific genes was analyzed. Genes preferentially expressed in both placenta and hemangiomas were identified, including 17-? hydroxysteroid dehydrogenase type 2 and tissue factor pathway inhibitor 2. These data demonstrate the value of global molecular profiling of tissues as a tool for hypothesis-driven research. Furthermore, it suggests that the unique self-limited growth of infantile hemangioma may, in fact, mirror the lifetime of placental endothelium.

Barnes, Carmen M.; Huang, Sui; Kaipainen, Arja; Sanoudou, Despina; Chen, Emy J.; Eichler, Gabriel S.; Guo, Yuchun; Yu, Ying; Ingber, Donald E.; Mulliken, John B.; Beggs, Alan H.; Folkman, Judah; Fishman, Steven J.



The origin of malignant malaria  

PubMed Central

Plasmodium falciparum, the causative agent of malignant malaria, is among the most severe human infectious diseases. The closest known relative of P. falciparum is a chimpanzee parasite, Plasmodium reichenowi, of which one single isolate was previously known. The co-speciation hypothesis suggests that both parasites evolved separately from a common ancestor over the last 5–7 million years, in parallel with the divergence of their hosts, the hominin and chimpanzee lineages. Genetic analysis of eight new isolates of P. reichenowi, from wild and wild-born captive chimpanzees in Cameroon and Côte d'Ivoire, shows that P. reichenowi is a geographically widespread and genetically diverse chimpanzee parasite. The genetic lineage comprising the totality of global P. falciparum is fully included within the much broader genetic diversity of P. reichenowi. This finding is inconsistent with the co-speciation hypothesis. Phylogenetic analysis indicates that all extant P. falciparum populations originated from P. reichenowi, likely by a single host transfer, which may have occurred as early as 2–3 million years ago, or as recently as 10,000 years ago. The evolutionary history of this relationship may be explained by two critical genetic mutations. First, inactivation of the CMAH gene in the human lineage rendered human ancestors unable to generate the sialic acid Neu5Gc from its precursor Neu5Ac, and likely made humans resistant to P. reichenowi. More recently, mutations in the dominant invasion receptor EBA 175 in the P. falciparum lineage provided the parasite with preference for the overabundant Neu5Ac precursor, accounting for its extreme human pathogenicity.

Rich, Stephen M.; Leendertz, Fabian H.; Xu, Guang; LeBreton, Matthew; Djoko, Cyrille F.; Aminake, Makoah N.; Takang, Eric E.; Diffo, Joseph L. D.; Pike, Brian L.; Rosenthal, Benjamin M.; Formenty, Pierre; Boesch, Christophe; Ayala, Francisco J.; Wolfe, Nathan D.



Malignant catarrhal fever: a review.  


Malignant catarrhal fever (MCF) is a fatal lymphoproliferative disease of cattle and other ungulates caused by the ruminant gamma-herpesviruses alcelaphine herpesvirus 1 (AlHV-1) and ovine herpesvirus 2 (OvHV-2). These viruses cause inapparent infection in their reservoir hosts (wildebeest for AlHV-1 and sheep for OvHV-2), but fatal lymphoproliferative disease when they infect MCF-susceptible hosts, including cattle, deer, bison, water buffalo and pigs. MCF is an important disease wherever reservoir and MCF-susceptible species mix and currently is a particular problem in Bali cattle in Indonesia, bison in the USA and in pastoralist cattle herds in Eastern and Southern Africa. MCF is characterised by the accumulation of lymphocytes (predominantly CD8(+) T lymphocytes) in a variety of organs, often associated with tissue necrosis. Only a small proportion of these lymphocytes appear to contain virus, although recent results with virus gene-specific probes indicate that more infected cells may be present than previously thought. The tissue damage in MCF is hypothesised to be caused by the indiscriminate activity of MHC-unrestricted cytotoxic T/natural killer cells. The pathogenesis of MCF and the virus life cycle are poorly understood and, currently, there is no effective disease control. Recent sequencing of the OvHV-2 genome and construction of an AlHV-1 bacterial artificial chromosome (BAC) are facilitating studies to understand the pathogenesis of this extraordinary disease. Furthermore, new and improved methods of disease diagnosis have been developed and promising vaccine strategies are being tested. The next few years are likely to be exciting and productive for MCF research. PMID:18760944

Russell, George C; Stewart, James P; Haig, David M



Unsuspected Extraocular Extension of Malignant Melanoma.  

National Technical Information Service (NTIS)

Pathology laboratories periodically receive eyes with obvious but clinically unsuspected extraocular extension of malignant melanoma. Several cases are presented that illustrate the importance of routinely inspecting enucleated eyes in the operating room....

A. P. Ferry



Improved radioimmunotherapy of hematologic malignancies. (Final report).  

National Technical Information Service (NTIS)

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 labo...

O. W. Press



Lymphangitis carcinomatosa complicating primary malignant peritoneal mesothelioma  

Microsoft Academic Search

A patient with malignant peritoneal mesothelioma and a diffuse pulmonary infiltrate is described. Computed tomographic scanning suggested lymphangitis carcinomatosa. This was confirmed on transbronchial biopsy to be due to metastatic mesothelioma.

P. S. Craft; M. S. Reading; S. Jain; R. A. ONeil



[Malignant polyps of the colon and rectum].  


It is important for the general surgeon to have a clear idea of what is a malignant polyp and factors determining its clinical management. A malignant polyp is either sessile or pedunculated and harbors an invasive carcinoma which means that malignant cells have penetrated into or through the muscularis mucosae. Carcinoma in situ, intramucosal carcinoma, superficial carcinoma, carcinoma within the the mucosa or lamina propria are terms commonly used that must be distinguished from true invasive malignancy. These polyps should be treated by complete polypectomy and followed up as in a benign polyp. A polyp with invasive carcinoma requires careful evaluation to make a decision if simple polypectomy is sufficient treatment or whether surgical treatment is indicated. This decision is based on the risk factors such as a residual/recurrent tumour and the risk of lymph node metastases. We present a current review of the literature on the subject. PMID:11037703

Bém, J; Jedlicka, J; Bém, S



New developments in surgery of malignant gliomas  

PubMed Central

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.

Vranic, Andrej



Long-term adaptive functioning outcomes of children with inherited metabolic and genetic diseases treated with hematopoietic stem cell transplantation in a single large pediatric center: parents' perspective.  


Over the past 2 decades, hematopoietic stem cell transplantation (HSCT) has been used as therapy for selected inherited metabolic and genetic diseases (IMGDs). The primary objective of HSCT for these disorders has been to promote long-term survival, optimize quality of life, and improve neurocognitive performance. We performed 45 HSCTs for 44 children with IMGDs (13 related and 32 unrelated); 24 HSCTs for 23 children with Hurler syndrome, 8 for malignant infantile osteopetrosis, 6 for X-linked adrenoleukodystrophy, 2 for metachromatic leukodystrophy, 2 for Gaucher disease, 1 for Ganglioside Monosialic Acid (GM) gangliosidosis, 1 for sialiosis (type 2), and 1 HSCT for Niemann-Pick type A. At a median follow-up of 7.2 years (range: 2.2 to 17.6 y) 18 of 23 patients with Hurler syndrome are alive, 15 attended regular school. Thirteen of 18 were ambulatory, 2 had mobility difficulties, and 1 uses wheelchair. For non-Hurler patients, 5 children suffered secondary graft failure and 4 of them died from progressive disease. The remaining children with osteopetrosis are alive and most children attended regular school. One out of the 4 survivors with adrenoleukodystrophy has been transferred to the adult follow-up clinic and he is in full-time employment. Parents' perspectives and expectations of HSCT in these IMGDs were positive and supportive to continue to offer HSCT for these disorders. PMID:21336168

Gassas, Adam; Raiman, Julian; White, Laura; Schechter, Tal; Clarke, Joe; Doyle, John



Malignant mesothelioma: attributable risk of asbestos exposure  

Microsoft Academic Search

OBJECTIVES--To evaluate a case-control study of malignant mesothelioma through patterns of exposure to asbestos based upon information from telephone interviews with next of kin. METHODS--Potential cases, identified from medical files and death certificates, included all people diagnosed with malignant mesothelioma and registered during 1975-1980 by the Los Angeles County Cancer Surveillance Program, the New York State Cancer Registry (excluding New

R Spirtas; E F Heineman; L Bernstein; G W Beebe; R J Keehn; A Stark; B L Harlow; J Benichou



Malignant peritoneal mesothelioma presenting with respiratory symptoms  

Microsoft Academic Search

.   Malignant peritoneal mesothelioma is a rare disease associated with mild, nonspecific abdominal symptoms and a wide spectrum\\u000a of imaging findings, with thickened mesentery and peritoneum being the most common ones. A case of a malignant peritoneal\\u000a mesothelioma presenting with manifestations of pulmonary disease is reported. Imaging evaluation revealed pleural, lung and\\u000a pericardial involvement together with retroperitoneal lymphadenopathy, little ascites

M. Daskalogiannaki; P. Prassopoulos; M. Raissaki; M. Tsardi; N. Gourtsoyiannis



Giant Chondroid Syringoma Radiologically Mimicking Malignancy  

PubMed Central

Chondroid syringoma, or mixed tumor of skin, is a relatively rare, usually benign sweat gland tumor, most often seen in the head-and-neck region. Rare malignant examples have been reported, commonly involving the extremities. We report here a case radiologically mimicking a malignant neoplasm, but histologically-proven benign subcutaneous chondroid syringoma, arising in the anterior aspect of the upper thigh of a 59-year-old male.

Uyar, Belkiz; Solak, Aynur; Sahin, Neslin; Bugdayci, Husnu



Malignant mesothelioma: Canadian perspective and research directions  

PubMed Central

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.

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.



Jugular vein thrombosis associated with distant malignancy.  

PubMed Central

We describe two patients who developed internal jugular vein thrombosis associated with primary malignant disease arising outside the neck, and in one patient it was the presenting feature. Computed tomography was performed and the findings characteristic of internal jugular vein thrombosis are illustrated. We conclude that malignant disease should be considered in patients presenting with spontaneous internal jugular vein thrombosis with no other predisposing factors and that computed tomography is of value in confirming the diagnosis. Images Figure 1 Figure 2

Carrington, B. M.; Adams, J. E.



Pediatric Malignancies: Synopsis of Current Imaging Techniques  

Microsoft Academic Search

The imaging evaluation of malignancies is directed towards the assessment of size, location and characterization of the neoplasm.\\u000a Imaging children necessitates additional attention to the dose of radiation, given the radiosensitivity and the expected longevity\\u000a of children. This chapter will present some of the latest technologies used to image pediatric malignancies, as well as methods\\u000a to evaluate the most common

Sabah Servaes; Monica Epelman; Avrum Pollock; Karuna Shekdar


Systemic sclerosis in association with multiple primary pulmonary malignancy--a marker of internal malignancy?  

PubMed Central

Multiple pulmonary malignancy is uncommon and has not been reported in association with systemic sclerosis. We now report such a case in which it is likely that the connective tissue disease occurred as a marker of the internal malignancy. Systemic sclerosis is not generally a reliable indicator of malignant change, but it is possible that in patients who are immunosuppressed, either therapeutically or inherently, the onset of systemic sclerosis should prompt investigation for an underlying cause. Images Figure 1 Figure 2

Goodfield, M. J.; Millard, L. G.



CDKL5 mutations cause infantile spasms, early onset seizures, and severe mental retardation in female patients  

PubMed Central

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.

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



Analysis of Globule Types in Malignant Melanoma  

PubMed Central

Objective To identify and analyze subtypes of globules based on size, shape, network connectedness, pigmentation, and distribution to determine which globule types and globule distributions are most frequently associated with a diagnosis of malignant melanoma. Design Retrospective case series of dermoscopy images with globules. Setting Private dermatology practices. Participants Patients in dermatology practices. Intervention Observation only. Main Outcome Measure Association of globule types with malignant melanoma. Results The presence of large globules (odds ratio [OR], 5.25) and globules varying in size (4.72) or shape (5.37) had the highest ORs for malignant melanoma among all globule types and combinations studied. Classical globules (dark, discrete, convex, and 0.10–0.20 mm) had a higher risk (OR, 4.20) than irregularly shaped globules (dark, discrete, and not generally convex) (2.89). Globules connected to other structures were not significant in the diagnosis of malignant melanoma. Of the different configurations studied, asymmetric clusters have the highest risk (OR, 3.02). Conclusions The presence of globules of varying size or shape seems to be more associated with a diagnosis of malignant melanoma than any other globule type or distribution in this study. Large globules are of particular importance in the diagnosis of malignant melanoma.

Xu, Jin; Gupta, Kapil; Stoecker, William V.; Krishnamurthy, Yamini; Rabinovitz, Harold S.; Bangert, Austin; Calcara, David; Oliviero, Margaret; Malters, Joseph M.; Drugge, Rhett; Stanley, R. Joe; Moss, Randy H.; Celebi, M. Emre



Oral non-squamous malignant tumors; diagnosis and treatment  

Microsoft Academic Search

Some 90% of oral cancers consist of squamous cell carcinomas that arise from the oral mucosa. The remaining 10% of malignancies consist of malignant melanomas, carcinomas of the intraoral salivary glands, sarcomas of the soft tis- sues and the bones, malignant odontogenic tumors, non-Hodgkin's lymphomas and metastases from primary tumors located elsewhere in the body. These malignancies will be briefly

Rutger van der Waal; Isaäc van der Waal


Expansion of the first polyalanine tract of the ARX gene in a boy presenting with generalized dystonia in the absence of infantile spasms  

Microsoft Academic Search

Mutations in the Aristaless-related homeobox (ARX) gene are associated with pleiotropic phenotypes including infantile spasms, mental retardation and dystonia. However, relatively consistent genotype–phenotype correlations have been emphasized in prior reports. We report a boy presenting with mental retardation, tonic seizures and dystonia but without infantile spasms. Gene sequencing detected an additional seven GCG repeats in the first polyalanine tract of

Yuko Shinozaki; Maki Osawa; Hiroshi Sakuma; Hirofumi Komaki; Eiji Nakagawa; Kenji Sugai; Masayuki Sasaki; Yuichi Goto



Clonal genomic alterations in glioma malignancy stages.  


Comparison of constitutional and tumor genotypes at chromosomal loci defined by restriction fragment length alleles has proven useful in determining the genomic position and tissue specificity of recessive mutations that predispose to cancer (Hansen, M.F., and Cavenee, W.K. Cancer Res., 47:5518-5527, 1987). Here we have applied this approach to 53 unrelated patients with glial tumors of varying histological malignancy grade. Loss of constitutional heterozygosity for loci on chromosome 10 was observed in 28 of 29 tumors histologically classified as glioblastoma (malignancy grade IV) whereas no similar losses were observed in any of 22 gliomas of lower malignancy grade. Examination of restriction fragment length alleles on other chromosomes revealed that loss of sequences on chromosomes 13, 17, or 22 had occurred at nonrandom frequencies and in at least one instance of each malignancy grade of adult glioma. The tumors in which loss of constitutional heterozygosity was observed were composed of one or a mixture of glial cell subtypes displaying astrocytic, oligodendrocytic, and/or ependymal differentiation. These results demonstrate a close association of the loss of chromosome 10 sequences with the most malignant histological stage of glioma and that glioblastoma arises as the clonal expansion of an earlier staged precursor. Furthermore they suggest that glioblastoma is a common phenotypic and malignancy terminus for glial tumors of various cellular subtypes which is reached through a common molecular pathway. This approach which involves the identification of malignancy stage specific somatic losses of heterozygosity provides a genotypic, rather than phenotypic, analysis of tumor progression. PMID:2901288

James, C D; Carlbom, E; Dumanski, J P; Hansen, M; Nordenskjold, M; Collins, V P; Cavenee, W K



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

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



Nonmyeloablative stem cell transplantation and cell therapy for malignant and non-malignant diseases  

Microsoft Academic Search

The conditioning prior to allogeneic stem cell transplantation was originally designed as a myeloablative conditioning, designed to eliminate malignant or genetically abnormal cells and then use the transplant procedure for rescue of the patients or to replace missing bone marrow products. However, allografts can induce effective graft vs. malignancy effects and can also eliminate undesirable hematopoietic stem cells in patients

I. B. Resnick; M. Y. Shapira; S. Slavin



Metachronous malignant mesothelioma and pulmonary adenocarcinoma.  


The prevalence of multiple primary malignant neoplasms in a single patient is reported in a wide variation. The co-existence of malignant mesothelioma and pulmonary carcinoma is a rare entity. Herein, we reported a 60-year-old man who was a retired employee and heavy smoker. He had a suspicious history of asbestos exposure. He complained of chest pain and computerized tomography revealed a mass in the lower lobe of left lung. The patient underwent a left lower lobectomy and was diagnosed as pulmonary adenocarcinoma. During follow-up two years after surgery, the patient complained of dyspnea and chest computerized tomography scan revealed right pleural effusion and diffuse pleural thickening. For the differential diagnosis, the patient underwent wedge biopsy from the right lower lobe and was diagnosed as epithelial diffuse malignant mesothelioma. The development of malignant pleural mesothelioma and lung carcinoma could be associated with asbestos exposure. However, a history of asbestos exposure is not required for the diagnosis. The influence of effective anticancer therapies that improve the survival rates and increase the population ages could be related to the occurrence of a second malignancy. PMID:23354805

Özbudak, ?rem Hicran; Özbudak, Ömer; Arslan, Gökhan; Erdo?an, Abdullah; Özb?l?m, Gülay



Aberrant DNA methylation in cutaneous malignancies.  


In recent years it has become evident that in addition to genetic mutations also epigenetic alterations are causally related to the development and progression of cancer. The epigenetic mechanism most relevant in the pathogenesis of cancer appears to be aberrant methylation of tumor-suppressor gene promoters associated with transcriptional downregulation. Malignancies arising in the skin are the most prevalent in humans. The most common are basal cell carcinoma (BCC), cutaneous squamous cell carcinoma (SCC), melanoma, and cutaneous lymphoma. The visibility and accessibility of cutaneous tumors facilitate the scientific study of sequential epigenetic alterations occurring during tumorigenesis and might make treatment of malignant skin lesions using locally applied demethylating agents possible. In this review, we summarize the current knowledge concerning alterations of DNA methylation in BCC, SCC, melanoma, and cutaneous lymphoma. Furthermore, the potential "epigenotoxic" effects of ultraviolet radiation, an environmental carcinogen implicated in the tumorigenesis of most cutaneous malignancies, will be discussed. From the limited number of investigations of promoter hypermethylation in cutaneous malignancies, it is already clear that a great number of potential tumor-suppressor genes are epigenetically silenced in skin cancer, including components of signaling pathways critical in the pathogenesis of these malignancies. PMID:16210089

van Doorn, Remco; Gruis, Nelleke A; Willemze, Rein; van der Velden, Pieter A; Tensen, Cornelis P



Asbestos exposure and malignant mesothelioma in Korea.  


Although importation of asbestos to Korea has decreased, there are growing concerns of its hazardous effects. This paper describes the use and occupational exposure to asbestos, and the incidence and mortality of malignant mesotheliomas in Korea. Asbestos raw material imports from other countries peaked between 1990 and 1995, but importation of asbestos-containing and -processed materials has steadily increased until now. A comprehensive exposure survey was conducted in Korea between 1995 and 2006. The average airborne asbestos concentration was lower than from other countries and steadily decreased during the study period. The number of malignant mesothelioma cases in Korea was 48 in 1998, 39 in 1999, 45 in 2000, 38 in 2001, and 46 in 2002. There were 334 deaths due to malignant mesothelioma and an average of 30.4 deaths per year between 1996 and 2006. The number of deaths attributed to malignant mesothelioma ranged from 16 cases in 1999 to 57 cases in 2006. The magnitude of asbestos-related health problems in Korea has been underestimated due to under-diagnosis, incomplete reports, and shorter duration of exposure. A nationwide surveillance system for asbestos exposure and malignant mesothelioma should therefore be implemented. PMID:19827900

Lee, Kyoung-Ho; Yoon, Hyung-Suk; Choi, Sang-Jun; Kang, Daehee



Malignant mesenterial mesothelioma in stroke patients.  


Mesothel is the cell lining of serosal surface of the pleura, peritoneum, pericardium, and testis. Malignant mesothelioma is a highly aggressive tumor from mesothel that has a tendency to grow rapidly and invade locally. Although the incidence of malignant mesenterial mesothelioma is not so high, the case fatality rate is very high. The aim of this case report is to report the rare and difficult case with several complications. A Balinese man, 64 years old, came with chief complaint of weakness, abdominal enlargement, and nausea, with history of previous liver disease. On physical examination were found a decrease of conciousness, subfebrile, abdominal distension, ascites, negative traube space, and paralysis of the left side of the body. Laboratory examination results showed leukocytosis, hypochromic-micrositic anemia, trombocytosis, hypoalbuminemia, increase of alkaline phosphatase, and mild hyponatremia. Abdominal USG showed intraperitoneal mass which some of them attach to abdominal wall, possibly from mesenterium and ascites, esophagogastroduodenoscopy (EGD) revealed reflux esofagitis and anthral erossive gastritis, skull CT scan showed small infarction at left parietal medulla and right basal ganglia, cytology showed spreaded and grouped mesothel with reactive lymphocyte and amorph back ground. FNAB result showed malignant mesothelioma, and normal colonoscopy. Based on the above data, the diagnoses were malignant mesenterial mesothelioma, reflux esofagitis and anthral erossive gastritis, and non hemorrhagic stroke. Malignant mesenterial mesothelioma should be considered in patient with the combination of unexplained ascites and abdominal pain. Although the result of treatment is very disappointing, the patient had to be treated optimally to increase quality of life. PMID:19151450

Budiyasa, Dewa Gde Agung; Wibawa, I Dewa Nyoman



[Ovarian epithelial malignant tumors in adolescence].  


Objective: Ovarian epithelial malignant tumors in adolescence.Design: Literature review with case reports.Setting: Department of Gynaecology and Obstetrics, Faculty of Medicine at Masaryk´s University and Fakulty Hospital Brno.Methods: Literature review on ovarian epithelial malignant tumors in adolescence, their epidemiology, diagnosis and therapy with illustrative case reports.Conclusion: The ovarian epithelial malignant tumors in the adolescence represent rare group of these diseases according to the data from the National Cancer Registry. However, it is a very sensitive area of oncogynecology, that requires highly personalized approach and the cooperation with patient´s family. The ovarian epithelial malignant tumors in the age group of 15-19 years show some differences from these diseases of adults and older women. The differences concern the extent of the disease at the time of the diagnosis, the histopathological characteristics of the tumors and the proportion surgical therapy and chemotherapy. The diagnostic algorithm requires the cooperation with the colleagues from pediatric gynecology and oncology. Due to the occurrence of localizated stages and good tumor differentiation prevails the monotherapy presented the surgical treatment, especially in the form of the radical fertility-preserving procedures. The care of the patients should be concentrated into the oncogynecological centres. Keywords: ovarian epithelial malignant tumors, adolescence, fertility sparing surgical treatment, chemotherapy. PMID:24874822

Miná?, L; Ivanová, Z; Jandáková, E



New human sodium/glucose cotransporter gene (KST1): identification, characterization, and mutation analysis in ICCA (infantile convulsions and choreoathetosis) and BFIC (benign familial infantile convulsions) families.  


Cotransporters represent a major class of proteins that make use of ion gradients to drive active transport of substrate into cells. A new human gene, KST1, encoding a member of the sodium/glucose cotransporter family, was identified onto human chromosome 16p12-p11. This genomic region contains a major gene responsible for a syndrome of infantile convulsions and paroxysmal dyskinesia (ICCA syndrome), inherited as an autosomal dominant trait, as well as for benign familial infantile convulsions (BFIC). The entire coding sequence of the human KST1 gene was determined using a combination of methods including in silico comparison of its rabbit orthologous DNA complementary to RNA (cDNA) to the corresponding human genomic sequences, reverse transcription-polymerase chain reaction on human brain RNA, 5' and 3' rapid amplification of cDNA ends. The gene is divided into 16 exons and the predicted protein of 675 amino acids contains 14 transmembrane domains. It shares significant homology to the sodium-glucose transporter 1 cotransporter proteins. An alternatively spliced transcript resulting from the skipping of exon 6 led to a predicted protein lacking the 4th transmembrane domain. As ion transporters are good candidates for a large variety of human diseases, including paroxysmal disorders, a mutation search was performed in four families with ICCA or BFIC syndromes. No pathogenic mutation was found, although several polymorphic variants with amino acids exchanges were identified. Due to its broad expression in human tissues, the human KST1 gene could be involved in several other diseases mapped to human chromosome 16p12-p11. PMID:12039040

Roll, Patrice; Massacrier, Annick; Pereira, Sandrine; Robaglia-Schlupp, Andrée; Cau, Pierre; Szepetowski, Pierre



Carisbamate acutely suppresses spasms in a rat model of symptomatic infantile spasms  

PubMed Central

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.

Ono, Tomonori; Moshe, Solomon L.; Galanopoulou, Aristea S.



Aberrant DNA methylation in malignant melanoma.  


Malignant melanoma remains one of the most deadly human cancers with no effective cures for metastatic disease. The poor efficacy of current therapy in advanced melanoma highlights the need for better understanding of molecular mechanisms contributing to the disease. Recent work has shown that epigenetic changes, including aberrant DNA methylation, lead to alterations in gene expression and are as important in the development of malignant melanoma as the specific and well-characterized genetic events. Reversion of these methylation patterns could thus lead to a more targeted therapy and are currently under clinical investigation. The purpose of this review is to compile recent information on aberrant DNA methylation of melanoma, to highlight key genes and molecular pathways in melanoma development, which have been found to be epigenetically altered and to provide insight as to how DNA methylation might serve as targeted treatment option as well as a molecular and prognostic marker in malignant melanoma. PMID:20418788

Schinke, Carolina; Mo, Yongkai; Yu, Yiting; Amiri, Kathy; Sosman, Jeff; Greally, John; Verma, Amit



Malignant peripheral nerve sheath tumors: an update.  


Malignant peripheral nerve sheath tumors (MPNSTs) are highly malignant cancers that account for approximately 5-10% of all soft t