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Sample records for gene clinical features

  1. LEOPARD Syndrome: Clinical Features and Gene Mutations

    PubMed Central

    Martínez-Quintana, E.; Rodríguez-González, F.

    2012-01-01

    The RAS/MAPK pathway proteins with germline mutations in their respective genes are associated with some disorders such as Noonan, LEOPARD (LS), neurofibromatosis type 1, Costello and cardio-facio-cutaneous syndromes. LEOPARD is an acronym, mnemonic for the major manifestations of this disorder, characterized by multiple lentigines, electrocardiographic abnormalities, ocular hypertelorism, pulmonic stenosis, abnormal genitalia, retardation of growth, and sensorineural deafness. Though it is not included in the acronym, hypertrophic cardiomyopathy is the most frequent cardiac anomaly observed, representing a potentially life-threatening problem in these patients. PTPN11, RAF1 and BRAF are the genes known to be associated with LS, identifying molecular genetic testing of the 3 gene mutations in about 95% of affected individuals. PTPN11 mutations are the most frequently found. Eleven different missense PTPN11 mutations (Tyr279Cys/Ser, Ala461Thr, Gly464Ala, Thr468Met/Pro, Arg498Trp/Leu, Gln506Pro, and Gln510Glu/Pro) have been reported so far in LS, 2 of which (Tyr279Cys and Thr468Met) occur in about 65% of the cases. Here, we provide an overview of clinical aspects of this disorder, the molecular mechanisms underlying pathogenesis and major genotype-phenotype correlations. PMID:23239957

  2. Modified Logistic Regression Models Using Gene Coexpression and Clinical Features to Predict Prostate Cancer Progression

    PubMed Central

    Zhao, Hongya; Logothetis, Christopher J.; Gorlov, Ivan P.; Zeng, Jia; Dai, Jianguo

    2013-01-01

    Predicting disease progression is one of the most challenging problems in prostate cancer research. Adding gene expression data to prediction models that are based on clinical features has been proposed to improve accuracy. In the current study, we applied a logistic regression (LR) model combining clinical features and gene co-expression data to improve the accuracy of the prediction of prostate cancer progression. The top-scoring pair (TSP) method was used to select genes for the model. The proposed models not only preserved the basic properties of the TSP algorithm but also incorporated the clinical features into the prognostic models. Based on the statistical inference with the iterative cross validation, we demonstrated that prediction LR models that included genes selected by the TSP method provided better predictions of prostate cancer progression than those using clinical variables only and/or those that included genes selected by the one-gene-at-a-time approach. Thus, we conclude that TSP selection is a useful tool for feature (and/or gene) selection to use in prognostic models and our model also provides an alternative for predicting prostate cancer progression. PMID:24367394

  3. Clinical features of patients with dystrophinopathy sharing the 45-55 exon deletion of DMD gene.

    PubMed

    Taglia, Antonella; Petillo, Roberta; D'Ambrosio, Paola; Picillo, Esther; Torella, Annalaura; Orsini, Chiara; Ergoli, Manuela; Scutifero, Marianna; Passamano, Luigia; Palladino, Alberto; Nigro, Gerardo; Politano, Luisa

    2015-05-01

    Becker muscular dystrophy (BMD) was first described in 1953 by Emile Becker as a benign variant of Duchenne muscular Dystrophy (DMD). Compared with DMD, BMD is clinically more heterogeneous, with initial presentation in the teenage years and loss of ambulation beyond the age of 16 and a wide spectrum of clinical presentations, ranging from only myalgias and muscle cramps to exercise intolerance and myoglobinuria, asymptomatic elevation of serum creatin-kinase, or mild limb-girdle weakness and quadriceps myopathy. About 50% of patients become symptomatic by the age of 10 and the most part by the age of 20 years. However few patients can be free of symptoms till their fifties and cases of late-onset Becker Muscular Dystrophy have also been described. In this report we describe the clinical features of patients with dystrophinopathy sharing a deletion of exons 45-55, occasionally or retrospectively diagnosed. These data are important for both the prognostic aspects of children presenting this dystrophin gene mutation, and for the genetic counseling in these families (reassuring them on the benign course of the disease), and last but not least to keep in mind a diagnosis of BMD in asymptomatic adults with mild hyperckemia. PMID:26155064

  4. Clinical features associated with copy number variations of the 14q32 imprinted gene cluster.

    PubMed

    Rosenfeld, Jill A; Fox, Joyce E; Descartes, Maria; Brewer, Fallon; Stroud, Tracy; Gorski, Jerome L; Upton, Sheila J; Moeschler, John B; Monteleone, Berrin; Neill, Nicholas J; Lamb, Allen N; Ballif, Blake C; Shaffer, Lisa G; Ravnan, J Britt

    2015-02-01

    Uniparental disomy (UPD) for imprinted chromosomes can cause abnormal phenotypes due to absent or overexpression of imprinted genes. UPD(14)pat causes a unique constellation of features including thoracic skeletal anomalies, polyhydramnios, placentomegaly, and limited survival; its hypothesized cause is overexpression of paternally expressed RTL1, due to absent regulatory effects of maternally expressed RTL1as. UPD(14)mat causes a milder condition with hypotonia, growth failure, and precocious puberty; its hypothesized cause is absence of paternally expressed DLK1. To more clearly establish how gains and losses of imprinted genes can cause disease, we report six individuals with copy number variations of the imprinted 14q32 region identified through clinical microarray-based comparative genomic hybridization. Three individuals presented with UPD(14)mat-like phenotypes (Temple syndrome) and had apparently de novo deletions spanning the imprinted region, including DLK1. One of these deletions was shown to be on the paternal chromosome. Two individuals with UPD(14)pat-like phenotypes had 122-154kb deletions on their maternal chromosomes that included RTL1as but not the differentially methylated regions that regulate imprinted gene expression, providing further support for RTL1 overexpression as a cause for the UPD(14)pat phenotype. The sixth individual is tetrasomic for a 1.7Mb segment, including the imprinted region, and presents with intellectual disability and seizures but lacks significant phenotypic overlap with either UPD(14) syndrome. Therefore, the 14q32 imprinted region is dosage sensitive, with deletions of different critical regions causing UPD(14)mat- and UPD(14)pat-like phenotypes, while copy gains are likely insufficient to recapitulate these phenotypes. PMID:25756153

  5. Clinical and Neuroimaging Features in Two Children with Mutations in the Mitochondrial ND5 Gene.

    PubMed

    Sonam, Kothari; Bindu, P S; Taly, Arun B; Govindaraju, Chikkanna; Gayathri, Narayanappa; Arvinda, Hanumanthapura R; Nagappa, Madhu; Sinha, Sanjib; Khan, Nahid Akthar; Govindaraj, Periyasamy; Thangaraj, Kumarasamy

    2015-08-01

    Mutations in the mitochondrial-encoded nicotinamide adenine dinucleotide dehydrogenase 5 gene (MT-ND5) has been implicated as an important genetic cause of childhood mitochondrial encephalomyopathies. This study reports the clinical and magnetic resonance imaging findings in two pediatric patients with mutations in the ND5 gene of mitochondrial DNA. The 8-month-old boy with m.13513 G>A mutation presented with infantile basal ganglia stroke syndrome secondary to mineralizing angiopathy. The 7-year-old girl with the m.13514A>G mutation had episodic regression, progressive ataxia, optic atrophy, and hyperactivity. Magnetic resonance imaging of the brain showed bilateral symmetrical signal intensity changes in the thalamus, tectal plate, and inferior olivary nucleus, which subsided on follow-up image. Both the patients had a stable course. Familiarity with the various phenotypic and magnetic resonance imaging findings and the clinical course in childhood mitochondrial encephalomyopathies may help the physician in targeted metabolic-genetic testing and prognostication. PMID:25974876

  6. Polymorphism in the IL4R gene and clinical features are associated with glioma prognosis

    PubMed Central

    Jin, Tian bo; Du, Shuli; Zhu, Xi kai; Li, Gang; Ouyang, Yongri; He, Na; Zhang, Zhiying; Zhang, Yuan; Kang, Longli; Yuan, Dongya

    2016-01-01

    Abstract Inflammatory gene polymorphisms may be associated with glioma risk. The purpose of this study was to analyze effects of certain inflammatory gene and some clinical factors on patient survival. The clinical information of 269 glioma patients conceived operation from September 2010 to May 2014 to decide the 1-, 3-year survival rates according to follow-up results and analyze age, gender, the WHO classification, extent of surgical resection, radiotherapy and chemotherapy factors effects on prognosis. Survival distributions were estimated by using the Kaplan–Meier method and difference in the survival was tested using the log-rank test. To estimate the association between the IL4, IL13, IL10, IL4R SNPs, and PFS and OS in glioma, the HR and 95% CI were calculated by univariate Cox proportional hazards model. Multivariate Cox model were performed to compute adjusted HR and 95% CI. All data was analyzed with SPSS17.0 package. Extent of surgical resection, chemotherapy, and age are an important factor in glioma overall survival and progression-free survival overall. Extent of surgery and chemotherapy are important factors in astrocytoma overall survival. Univariate analysis showed that IL4R rs1801275 was significantly associated with overall survival of glioma and astrocytoma patients (P < 0.05). Multivariate Cox regression analysis showed that IL4R rs1801275 GG genotype could increase the death risk of glioma and astrocytoma patients (Glioma: hazard ratio [HR]: 4.897, 95% confidence limits [95% CI]: 1.962–12.222, P = 0.001; Astrocytoma: HR: 15.944, 95% CI: 4.019–63.253, P < 0.05). Our research results showed that extent of surgical resection, age, and chemotherapy affect the prognosis of glioma. The IL4R gene may affect the survival of glioma patients. PMID:27495027

  7. 1p13.2 deletion displays clinical features overlapping Noonan syndrome, likely related to NRAS gene haploinsufficiency.

    PubMed

    Linhares, Natália Duarte; Freire, Maíra Cristina Menezes; Cardenas, Raony Guimarães Corrêa do Carmo Lisboa; Pena, Heloisa Barbosa; Lachlan, Katherine; Dallapiccola, Bruno; Bacino, Carlos; Delobel, Bruno; James, Paul; Thuresson, Ann-Charlotte; Annerén, Göran; Pena, Sérgio D J

    2016-08-01

    Deletion-induced hemizygosity may unmask deleterious autosomal recessive variants and be a cause of the phenotypic variability observed in microdeletion syndromes. We performed complete exome sequencing (WES) analysis to examine this possibility in a patient with 1p13.2 microdeletion. Since the patient displayed clinical features suggestive of Noonan Syndrome (NS), we also used WES to rule out the presence of pathogenic variants in any of the genes associated with the different types of NS. We concluded that the clinical findings could be attributed solely to the 1p13.2 haploinsufficiency. Retrospective analysis of other nine reported patients with 1p13.2 microdeletions showed that six of them also presented some characteristics of NS. In all these cases, the deleted segment included the NRAS gene. Gain-of-function mutations of NRAS gene are causally related to NS type 6. Thus, it is conceivable that NRAS haploinsufficiency and gain-of-function mutations may have similar clinical consequences. The same phenomenon has been described for two other genes belonging to the Ras/MAPK pathway: MAP2K2 and SHOC2. In conclusion, we here report genotype-phenotype correlations in patients with chromosome 1p13.2 microdeletions and we propose that NRAS may be a critical gene for the NS characteristics in the patients. PMID:27494202

  8. 1p13.2 deletion displays clinical features overlapping Noonan syndrome, likely related to NRAS gene haploinsufficiency.

    PubMed

    Linhares, Natália Duarte; Freire, Maíra Cristina Menezes; Cardenas, Raony Guimarães Corrêa do Carmo Lisboa; Pena, Heloisa Barbosa; Lachlan, Katherine; Dallapiccola, Bruno; Bacino, Carlos; Delobel, Bruno; James, Paul; Thuresson, Ann-Charlotte; Annerén, Göran; Pena, Sérgio D J

    2016-01-01

    Deletion-induced hemizygosity may unmask deleterious autosomal recessive variants and be a cause of the phenotypic variability observed in microdeletion syndromes. We performed complete exome sequencing (WES) analysis to examine this possibility in a patient with 1p13.2 microdeletion. Since the patient displayed clinical features suggestive of Noonan Syndrome (NS), we also used WES to rule out the presence of pathogenic variants in any of the genes associated with the different types of NS. We concluded that the clinical findings could be attributed solely to the 1p13.2 haploinsufficiency. Retrospective analysis of other nine reported patients with 1p13.2 microdeletions showed that six of them also presented some characteristics of NS. In all these cases, the deleted segment included the NRAS gene. Gain-of-function mutations of NRAS gene are causally related to NS type 6. Thus, it is conceivable that NRAS haploinsufficiency and gain-of-function mutations may have similar clinical consequences. The same phenomenon has been described for two other genes belonging to the Ras/MAPK pathway: MAP2K2 and SHOC2. In conclusion, we here report genotype-phenotype correlations in patients with chromosome 1p13.2 microdeletions and we propose that NRAS may be a critical gene for the NS characteristics in the patients. PMID:27561113

  9. 1p13.2 deletion displays clinical features overlapping Noonan syndrome, likely related to NRAS gene haploinsufficiency

    PubMed Central

    Linhares, Natália Duarte; Freire, Maíra Cristina Menezes; Cardenas, Raony Guimarães Corrêa do Carmo Lisboa; Pena, Heloisa Barbosa; Lachlan, Katherine; Dallapiccola, Bruno; Bacino, Carlos; Delobel, Bruno; James, Paul; Thuresson, Ann-Charlotte; Annerén, Göran; Pena, Sérgio D. J.

    2016-01-01

    Abstract Deletion-induced hemizygosity may unmask deleterious autosomal recessive variants and be a cause of the phenotypic variability observed in microdeletion syndromes. We performed complete exome sequencing (WES) analysis to examine this possibility in a patient with 1p13.2 microdeletion. Since the patient displayed clinical features suggestive of Noonan Syndrome (NS), we also used WES to rule out the presence of pathogenic variants in any of the genes associated with the different types of NS. We concluded that the clinical findings could be attributed solely to the 1p13.2 haploinsufficiency. Retrospective analysis of other nine reported patients with 1p13.2 microdeletions showed that six of them also presented some characteristics of NS. In all these cases, the deleted segment included the NRAS gene. Gain-of-function mutations of NRAS gene are causally related to NS type 6. Thus, it is conceivable that NRAS haploinsufficiency and gain-of-function mutations may have similar clinical consequences. The same phenomenon has been described for two other genes belonging to the Ras/MAPK pathway: MAP2K2 and SHOC2. In conclusion, we here report genotype-phenotype correlations in patients with chromosome 1p13.2 microdeletions and we propose that NRAS may be a critical gene for the NS characteristics in the patients. PMID:27561113

  10. Novel Mutation of the GNE Gene Presenting Atypical Mild Clinical Feature: A Korean Case Report.

    PubMed

    Choi, Young-Ah; Park, Sung-Hye; Yi, Youbin; Kim, Keewon

    2015-06-01

    Glucosamine (UDP-N-acetyl)-2-epimerase/N-acetylmannosamine kinase (GNE) myopathy is caused by mutations in GNE, a key enzyme in sialic acid biosynthesis. Here, we reported a case of GNE that presented with atypical mild clinical feature and slow progression. A 48-year-old female had a complaint of left foot drop since the age of 46 years. Electromyography (EMG) and muscle biopsy from left tibialis anterior muscle were compatible with myopathy. Genetic analysis led to the identification of c.1714G>C/c.527A>T compound heterozygous mutation, which is the second most frequent mutation in Japan as far as we know. Previous research has revealed that c.1714G>C/c.527A>T compound heterozygous mutation is a mild mutation as the onset of the disease is much later than the usual age of onset of GNE myopathy and the clinical course is slowly progressive. This was the first case report in Korea of the clinicopathological characteristics of GNE myopathy with GNE (c.1714G>C/c.527A>T compound heterozygous) mutation. PMID:26161358

  11. Fibroid-associated heavy menstrual bleeding: correlation between clinical features, Doppler ultrasound assessment of vasculature, and tissue gene expression profiles.

    PubMed

    Tsiligiannis, Sophia E; Zaitseva, Marina; Coombs, Peter R; Shekleton, Paul; Olshansky, Moshe; Hickey, Martha; Vollenhoven, Beverley; Rogers, Peter A W

    2013-04-01

    Despite the prevalence of uterine fibroids (Fs), few studies have investigated the links between clinical features and the cellular or molecular mechanisms that drive F growth and development. Such knowledge will ultimately help to differentiate symptomatic from asymptomatic Fs and could result in the development of more effective and individualized treatments. The aim of this study was to investigate the relationship between ultrasound appearance, blood flow, and angiogenic gene expression in F, perifibroid (PM), and distant myometrial (DM) tissues. We hypothesized that angiogenic gene expression would be increased in tissues and participants that showed increased blood flow by Doppler ultrasound. The study was performed using Doppler ultrasound to measure blood flow prior to hysterectomy, with subsequent tissue samples from the F, PM, and DM being investigated for angiogenic gene expression. Overall, PM blood flow (measured as peak systolic velocity [PSV]) was higher than F blood flow, although significant heterogeneity was seen in vascularity and blood flow between different Fs and their surrounding myometrium. We did not find any correlation between PSV and any other clinical or molecular parameter in this study. We identified 19 angiogenesis pathway-related genes with significant differences in expression between F and DM, and 2 genes, matrix metalloproteinase 9 (MMP9) and Neuropilin 2 (NRP2), that were significantly different between F and PM. These results are consistent with subtle differences between PM and DM. Understanding the differences between symptomatic versus asymptomatic Fs may eventually lead to more effective treatments that directly target the source of heavy menstrual bleeding. PMID:22995988

  12. Association of the Brain-derived Neurotrophic Factor Gene and Clinical Features of Bipolar Disorder in Korea

    PubMed Central

    Min, Hye Ji; Cho, Hyun-Sang; Kim, Se Joo; Seok, Jeong-Ho; Lee, Eun

    2012-01-01

    Objective Brain-derived neurotrophic factor (BDNF) plays an important role in cell survival, differentiation, and cell death as well as in neural plasticity. Recent studies have suggested that BDNF is involved in the pathogenesis of bipolar disorder. The aim of this study was to investigate the association of the genetic variations of the BDNF gene with bipolar disorder in Korea. We also studied the possible association of these genetic variants with clinical features. Methods The allelic and genotypic distributions of Val66Met polymorphism of the BDNF gene were analyzed using a polymerase chain reaction-based method in 184 bipolar patients and 214 controls. Analysis was performed to investigate an association of the Val66Met polymorphism of the BDNF gene and the clinical features in bipolar patients. Results No significant difference was found between bipolar patients and controls in the genotype and allele frequencies for the investigated BDNF polymorphism. However, the age of onset of bipolar disorder among the Val/Val (25.57), Val/Met (30.42) and Met/Met (32.45) genotype groups were significantly different (p=0.037). Conclusion This study suggests that Val66Met polymorphisms are unlikely to contribution to the genetic predisposition to bipolar disorder as a whole. But Val66Met polymorphism may be associated with age of onset of the disorder, further studies designed to investigate the relationship in a larger population may be warranted. PMID:23430274

  13. Two distinct clinical features and cognitive impairment in amyotrophic lateral sclerosis patients with TARDBP gene mutations in the Chinese population.

    PubMed

    Ju, XiaoDong; Liu, WenChao; Li, XiaoGang; Liu, Na; Zhang, Nan; Liu, Tao; Deng, Min

    2016-02-01

    Mutations in the TARDBP gene have been identified as a major causative factor in amyotrophic lateral sclerosis (ALS). However, few reports have analyzed the relationship of genotype-phenotype, especially in Chinese ALS patients. Our study investigated the presence and frequency of TARDBP mutations in Chinese patients with ALS. Additionally, we investigated correlations among clinical features and TARDBP gene mutations in a large ALS family with the p.M337 V mutation and one sporadic ALS (SALS) patient with the p.S393 L mutation. The pedigree with the p.M337 V mutation showed variable clinical features with a long lifespan, particularly cognitive impairment. One patient carrying the p.S393 L mutation experienced ALS with cognitive impairment; the patient also had a family history of frontotemporal dementia (FTD). This is the first report of detailed genetic and clinical characterizations of the TARDBP gene in a Chinese population. This research is also the first to demonstrate that the p.M337 V and the p.S393 L mutations are related to cognitive impairment in ALS patients. The mutation frequency of TARDBP was 5.6% in Chinese, SOD1-negative familial ALS (FALS), which was much higher than that reported in previous studies conducted with Caucasian populations, whereas the TARDBP mutation frequency was lower in the Chinese population with regard to SALS patients. Our results emphasize the importance of the genetic and clinical characterization of TARDBP mutations in ALS, which allows us to understand the genotype-phenotype relationship and relative frequencies in different populations. PMID:26639158

  14. Clinical features of X linked juvenile retinoschisis in Chinese families associated with novel mutations in the RS1 gene

    PubMed Central

    Ma, Xiang; Tao, Yong

    2007-01-01

    Purpose To describe the clinical phenotype of X linked juvenile retinoschisis (XLRS) in 12 Chinese families with 11 different mutations in the XLRS1 (RS1) gene. Methods Complete ophthalmic examinations were carried out in 29 affected males (12 probands), 38 heterozygous females carriers, and 100 controls. The coding regions of the RS1 gene that encodes retinoschisin were amplified by polymerase chain reaction and directly sequenced. Results Of the 29 male participants, 28 (96.6%) displayed typical foveal schisis. Eleven different RS1 mutations were identified in 12 families; four of these mutations, two frameshift mutations (26 del T of exon 1 and 488 del G of exon 5), and two missense mutations (Asp145His and Arg156Gly) of exon 5, had not been previously described. One non-disease-related polymorphism (NSP): 576C to T (Pro192Pro) change was also newly reported herein. We compared genotypes and observed more severe clinical features in families with the following mutations: frameshift mutation (26 del T) of exon 1, the splice donor site mutation (IVS1+2T to C),or Arg102Gln, Arg209His, and Arg213Gln mutations. Conclusions Severe XLRS phenotypes are associated with the frameshift mutation 26 del T, splice donor site mutation (IVS1+2T to C), and Arg102Gln, Asp145His, Arg209His, and Arg213Gln mutations. The wide variability in the phenotype in Chinese patients with XLRS and different mutations in the RS1 gene is described. Identification of mutations in the RS1 gene and expanded information on clinical manifestations will facilitate early diagnosis, appropriate early therapy, and genetic counseling regarding the prognosis of XLRS. PMID:17615541

  15. Altered Autophagy-Associated Genes Expression in T Cells of Oral Lichen Planus Correlated with Clinical Features

    PubMed Central

    Tan, Ya-Qin; Zhang, Jing; Du, Ge-Fei; Lu, Rui; Chen, Guan-Ying; Zhou, Gang

    2016-01-01

    Oral lichen planus (OLP) is a T cell-mediated inflammatory autoimmune disease. Autophagy has emerged as a fundamental trafficking event in mediating T cell response, which plays crucial roles in innate and adaptive immunity. The present study mainly investigated the mRNA expression of autophagy-associated genes in peripheral blood T cells of OLP patients and evaluated correlations between their expression and the clinical features of OLP. Five differentially expressed autophagy-associated genes were identified by autophagy array. Quantitative real-time RT-PCR results confirmed that IGF1 expression in the peripheral blood T cells of OLP patients was significantly higher than that in controls, especially in female and middle-aged (30–50 years old) OLP patients. In addition, ATG9B mRNA levels were significantly lower in nonerosive OLP patients. However, no significant differences were found in the expression of HGS, ESR1, and SNCA between OLP patients and controls. Taken together, dysregulation of T cell autophagy may be involved in immune response of OLP and may be correlated with clinical patterns. PMID:26980945

  16. Correlation of clinical features and methylation status of MGMT gene promoter in glioblastomas.

    PubMed

    Blanc, J L; Wager, M; Guilhot, J; Kusy, S; Bataille, B; Chantereau, T; Lapierre, F; Larsen, C J; Karayan-Tapon, L

    2004-07-01

    In an effort to extend the potential relationship between the methylation status of MGMT promoter and response to CENU therapy, we examined the methylation status of MGMT promoter in 44 patients with glioblastomas. Tumor specimens were obtained during surgery before adjuvant treatment, frozen and stored at -80 degrees C until for DNA extraction process. DNA methylation patterns in the CpG island of the MGMT gene were determined in every tumor by methylation specific PCR (MSP). These results were then related to overall survival and response to alkylating agents using statistical analysis. Methylation of the MGMT promoter was detected in 68% of tumors, and 96.7% of methylated tumors exhibited also an unmethylated status. There was no relationship between the methylation status of the MGMT promoter and overall survival and response to alkylating agents. Our observations do not lead us to consider promoter methylation of MGMT gene as a prognostic factor of responsiveness to alkylating agents in glioblastomas. PMID:15332332

  17. Clinical features of actinomycosis

    PubMed Central

    Bonnefond, Simon; Catroux, Mélanie; Melenotte, Cléa; Karkowski, Ludovic; Rolland, Ludivine; Trouillier, Sébastien; Raffray, Loic

    2016-01-01

    Abstract Actinomycosis is a rare heterogeneous anaerobic infection with misleading clinical presentations that delay diagnosis. A significant number of misdiagnosed cases have been reported in specific localizations, but studies including various forms of actinomycosis have rarely been published. We performed a multicenter retrospective chart review of laboratory-confirmed actinomycosis cases from January 2000 until January 2014. We described clinical characteristics, diagnostic procedures, differential diagnosis, and management of actinomycosis of clinical significance. Twenty-eight patients were included from 6 hospitals in France. Disease was diagnosed predominately in the abdomen/pelvis (n = 9), orocervicofacial (n = 5), cardiothoracic (n = 5), skeletal (n = 3), hematogenous (n = 3), soft tissue (n = 2), and intracranially (n = 1). Four patients (14%) were immunocompromised. In most cases (92 %), the diagnosis of actinomycosis was not suspected on admission, as clinical features were not specific. Diagnosis was obtained from either microbiology (50%, n = 14) or histopathology (42%, n = 12), or from both methods (7%, n = 2). Surgical biopsy was needed for definite diagnosis in 71% of cases (n = 20). Coinfection was found in 13 patients (46%), among which 3 patients were diagnosed from histologic criteria only. Two-thirds of patients were treated with amoxicillin. Median duration of antibiotics was 120 days (interquartile range 60–180), whereas the median follow-up time was 12 months (interquartile range 5.25–18). Two patients died. This study highlights the distinct and miscellaneous patterns of actinomycosis to prompt accurate diagnosis and earlier treatments, thus improving the outcome. Surgical biopsy should be performed when possible while raising histologist's and microbiologist's awareness of possible actinomycosis to enhance the chance of diagnosis and use specific molecular methods. PMID:27311002

  18. Mutation of NPM1 and FLT3 Genes in Acute Myeloid Leukemia and Their Association with Clinical and Immunophenotypic Features

    PubMed Central

    Chauhan, Pradeep Singh; Ihsan, Rakhshan; Singh, L. C.; Gupta, Dipendra Kumar; Mittal, Vishakha; Kapur, Sujala

    2013-01-01

    Background. Mutations in NPM1 and FLT3 genes represent the most frequent genetic alterations and important diagnostic and prognostic indicators in patients with acute myeloid leukemia (AML). Objective. We investigated the prevalence and clinical characteristics of NPM1 and FLT3 mutations in 161 patients of de novo AML including adults and children. Results. NPM1 mutation was found in 21% and FLT3 mutation in 25% of the AML patients. Thirteen (8%) samples were positive for both NPM1 and FLT3/ITD mutations. Adult patients had significantly higher frequency of NPM1 mutation than children (25.8% versus 8.8%; P = 0.02). Further, NPM1 mutation was found to be more frequent in patients above 45 years of age (P = 0.02). NPM1 mutation was significantly associated with higher platelet count (P = 0.05) and absence of hepatosplenomegaly (P = 0.01), while FLT3/ITD mutation was associated with higher white blood count (P = 0.01). Immunophenotypically, NPM1 mutation was associated with the lack of CD34 (P < 0.001) and HLD-DR expression (P < 0.001), while FLT3/ITD mutation was positively associated with the expression of CD7 (P = 0.04). No correlation was found between NPM1 mutation and fusion gene. Interestingly, FLT3/ITD mutation was found to be inversely associated with AML/ETO fusion gene (P = 0.04). Conclusions. The results suggest that distinct clinical and immunophenotypic characteristics of NPM1 and FLT3/ITD mutations present further insight into the molecular mechanism of leukemogenesis. PMID:24288427

  19. The importance of HLA DRB1 gene allele to clinical features and disability in patients with multiple sclerosis in Lithuania

    PubMed Central

    2013-01-01

    Background The association of HLA DRB1 alleles with susceptibility to multiple sclerosis (MS) has been consistently reported although its effect on the clinical features and disability is still unclear probably due to diversity in ethnicity and geographic location of the studied populations. The aim of the present study was to investigate the influence of HLA DRB1 alleles on the clinical features and disability of the patients with MS in Lithuania. Methods This was a prospective study of 120 patients with MS. HLA DRB1 alleles were genotyped using the polymerase chain reaction. Results The first symptoms of MS in patients with HLA DRB1*15 allele manifested at younger age than in those without this allele (28.32 +/− 5.49 yrs vs. 30.94 +/− 8.43 yrs, respectively, p = 0.043). HLA DRB1*08 allele was more prevalent among relapsing-remitting (RR) MS patients than among patients with progressive course of MS (25.0% vs. 8.3%, respectively, chi^2 = 6.000, p = 0.05). MS patients with this allele had lower relapse rate than those without this allele (1.00 +/− 0.97 and 1.44 +/− 0.85, respectively, p = 0.043). Degree of disability during the last visit was lower among the patients with HLA DRB1*08 allele (EDSS score 3.15 +/− 1.95 vs. 4.49 +/− 1.96, p = 0.006), and higher among those with HLA DRB1*15 allele (EDSS score 4.60 +/− 2.10 vs.4.05 +/− 1.94, p = 0.047) compared to patients without these alleles but there were no significant associations between these alleles and the duration of the disease to disability. HLA DRB1*08 allele (OR = 0.18, 95% CI 0,039-0,8, p = 0.029) was demonstradet to be independent factor to take a longer time to reach an EDSS of 6, while HLA DRB1*01 allele (OR = 5.92, 95% CI 1,30-26,8, p = 0.021) was related in a shorter time to reach and EDSS of 6. Patients with HLA DRB1*08 allele had lower IgG index compared to patients without this allele (0.58 +/− 0.17 and 0.73 +/− 0.31, respectively, p

  20. Feature++: Automatic Feature Construction for Clinical Data Analysis.

    PubMed

    Sun, Wen; Hao, Bibo; Yu, Yiqin; Li, Jing; Hu, Gang; Xie, Guotong

    2016-01-01

    With the rapid growth of clinical data and knowledge, feature construction for clinical analysis becomes increasingly important and challenging. Given a clinical dataset with up to hundreds or thousands of columns, the traditional manual feature construction process is usually too labour intensive to generate a full spectrum of features with potential values. As a result, advanced large-scale data analysis technologies, such as feature selection for predictive modelling, cannot be fully utilized for clinical data analysis. In this paper, we propose an automatic feature construction framework for clinical data analysis, namely, Feature++. It leverages available public knowledge to understand the semantics of the clinical data, and is able to integrate external data sources to automatically construct new features based on predefined rules and clinical knowledge. We demonstrate the effectiveness of Feature++ in a typical predictive modelling use case with a public clinical dataset, and the results suggest that the proposed approach is able to fulfil typical feature construction tasks with minimal dataset specific configurations, so that more accurate models can be obtained from various clinical datasets in a more efficient way. PMID:27577443

  1. Clinical and pathological features of Burkitt lymphoma showing expression of BCL2--an analysis including gene expression in formalin-fixed paraffin-embedded tissue.

    PubMed

    Masqué-Soler, Neus; Szczepanowski, Monika; Kohler, Christian W; Aukema, Sietse M; Nagel, Inga; Richter, Julia; Siebert, Reiner; Spang, Rainer; Burkhardt, Birgit; Klapper, Wolfram

    2015-11-01

    The differential diagnosis between Burkitt lymphoma (BL) and diffuse large B-cell lymphoma (DLBCL) can be challenging. BL has been reported to express less BCL2 than DLBCL, but this issue has not been analysed systematically. BL expressing BCL2 can be considered to be MYC/BCL2 co-expressors, a feature that is associated with poorer outcome in DLBCL but that has not been correlated with outcome in BL so far. We analysed the expression of BCL2 in 150 cases of conventionally diagnosed BL using two different BCL2 antibodies. BCL2 expression was detected in 23% of the cases, though the expression varied in intensity and number of positive cells. We did not detect any relevant differences in clinical presentation and outcome between BCL2-positive and BCL2-negative BL in a subgroup of 43 cases for which detailed clinical data were available. An independent cohort of 17 BL with expression of BCL2 were analysed molecularly, with 13 of 17 cases classified as molecularly defined BL (Burkitt Lymphoma) using gene expression profiling on formalin-fixed paraffin-embedded tissues. The four lymphomas diagnosed molecularly as intermediates did not differ in clinical presentation and outcome from molecularly defined BL. PMID:26218299

  2. Rs4948496 within ARID5B gene is associated with clinical features of systemic lupus erythematosus in the Chinese Han population.

    PubMed

    Jiang, Long; Wu, Jianping; Li, Weiran; Du, Juan; Wang, Wenjun; Zhu, Zhengwei; Gao, Jinping; Sheng, Yujun; Yin, Xianyong; Zheng, Xiaodong; Li, Hui; Li, Yang; Meng, Li; Fan, Xing; Liu, Shengxiu; Zeng, Ming; Wang, Zaixing; Cui, Yong; Tang, Huayang; Sun, Liangdan; Yang, Sen; Zhang, Xuejun

    2015-06-01

    In our previous meta-analysis of genome-wide association study, we identified the single nucleotide polymorphism (SNP) rs4948496 (P = 5.1 × 10(-11) , odds ratio [OR] = 0.85) within the ARID5B gene associated with systemic lupus erythematosus (SLE) in a Chinese population. To investigate its association with disease subphenotypes, we further analyzed the genotype data of rs4948496 in 4348 cases and 6679 controls from our previous meta-analysis and an independent replication cohort in this study. The SNP rs4948496 was significantly associated with SLE (P = 1.61 × 10(-5) , OR = 0.88, 95% confidence interval [CI] = 0.83-0.93) in our group. In case-only study, the genotype of rs4948496 was associated with antinuclear antibodies (P = 0.03, OR = 0.81, 95% CI = 0.68-0.98) and anti-RNP (P = 0.03, OR = 0.86, 95% CI = 0.76-0.99). This study showed that rs4948496 in ARID5B is associated with several subphenotypes of SLE and this gene may cause the complicacy of clinical features. PMID:25808444

  3. Dermoscopic and clinical features of trunk melanomas

    PubMed Central

    Emiroglu, Nazan; Hofmann-Wellenhof, Rainer

    2014-01-01

    Introduction Malignant melanomas account for 5% of all skin cancers and usually have a fatal clinical course. Additionally, the incidence of melanoma increases more rapidly than in any other cancer, and this has been attributed to the development of highly sensitive diagnostic techniques, mainly dermoscopy, which allows for early diagnosis. The phenotypic manifestations of gene/environment interactions, environmental factor and genetic factors may determine subtypes and anatomic localization of melanoma. Histopathologic subtypes, risk factors, and thickness of the skin are different in trunk melanomas. Aim To determine the frequency of dermatoscopic features in trunk melanomas. This study also investigates dermoscopic features according to the diameter of lesions. Material and methods Seventy-one trunk melanomas were included. Their dermoscopic and clinical images, histopathological and clinical data were assessed. The relations between the diameter, Breslow thickness and dermoscopic characteristics were evaluated. Results The most common dermoscopic findings of trunk melanomas were the multicomponent pattern (55 patients, 77.5%), asymmetry (62 patients; 87.3%), blue-gray veil (59 patients, 83.1%), and color variety (56 patients, 78.8%). When dermoscopic findings were compared, a multicomponent pattern (p = 0.03), milky-red areas (p = 0.001), blue-gray veils (p = 0.023), and regression structures (p = 0.037) were more common in large melanomas than in small melanomas. Conclusions The most common dermoscopic findings of trunk melanomas were the multicomponent pattern, asymmetry and blue-gray veil, color variety. The multicomponent pattern, milky-red areas, blue-gray veils, regression structures were statistically significant dermoscopic features in a group of large-diameter melanomas, compared to small melanomas. PMID:25610350

  4. Rosacea: clinical features and treatment.

    PubMed

    Lavers, Isabel

    2016-03-30

    Rosacea is a chronic inflammatory skin condition that predominantly affects the central face. It is characterised by a variable range of symptoms, including erythema, telangiectasia, papules, pustules and changes in skin texture. Rosacea may be transient, recurrent or persistent. Because it affects the most visible part of the body, the psychosocial effects of this condition can be significant. This article describes the features and management of the condition. PMID:27027198

  5. Clinical features of gastroenteropancreatic tumours

    PubMed Central

    Czarnywojtek, Agata; Bączyk, Maciej; Ziemnicka, Katarzyna; Fischbach, Jakub; Wrotkowska, Elżbieta; Ruchała, Marek

    2015-01-01

    Gastroenteropancreatic (GEP) endocrine tumours (carcinoids and pancreatic islet cell tumours) are composed of multipotent neuroendocrine cells that exhibit a unique ability to produce, store, and secrete biologically active substances and cause distinct clinical syndromes. The classification of GEP tumours as functioning or non-functioning is based on the presence of symptoms that accompany these syndromes secondary to the secretion of hormones, neuropeptides and/or neurotransmitters (functioning tumours). Non-functioning tumours are considered to be neoplasms of neuroendocrine differentiation that are not associated with obvious symptoms attributed to the hypersecretion of metabolically active substances. However, a number of these tumours are either capable of producing low levels of such substances, which can be detected by immunohistochemistry but are insufficient to cause symptoms related to a clinical syndrome, or alternatively, they may secrete substances that are either metabolically inactive or inappropriately processed. In some cases, GEP tumours are not associated with the production of any hormone or neurotransmitter. Both functioning and non-functioning tumours can also produce symptoms due to mass effects compressing vital surrounding structures. Gastroenteropancreatic tumours are usually classified further according to the anatomic site of origin: foregut (including respiratory tract, thymus, stomach, duodenum, and pancreas), midgut (including small intestine, appendix, and right colon), and hindgut (including transverse colon, sigmoid, and rectum). Within these subgroups the biological and clinical characteristics of the tumours vary considerably, but this classification is still in use because a significant number of previous studies, mainly observational, have used it extensively. PMID:26516377

  6. [Clinical features of Wei Yuheng].

    PubMed

    Yu, Zhong-yuan

    2006-04-01

    Wei Yuheng held that the endogenous miscellaneous diseases are mostly caused by liver diseases, highly stressed the treating method of nourishing yin to generate liver. He claimed that liver deficiency is mostly caused by congenital factors, sexual strain or improper treatment. He criticized that the improper treatment by elder generations mainly was caused by their ignorance of tonifying the liver based on the saying of "no tonifying treatment for the liver". Wei Yuheng's medical theories and clinical experiences are scattered in his book Xu Mingyi Lei'an (Supplement to Classified Case Records of Celebrated Physicians). Wang Mengying collected part of his thoughts and experiences and wrote the book Liuzhou Yihua (Liuzhou Medical Talks). Although Wang Mengying's book could deduce part of the thoughts of Wei Yuheng, it didn't disclose his theories completely. It is known to all that the compound recipe Yiguan Jian is a representative formula of Wei Yuheng to tonify liver yin. Actually, it can be concluded from the analysis of Xu Mingyi Lei'an that he used Fructus Lycii (Gouqi) as a main herb to tonify liver yin in the method of nourishing yin to generate liver. Based on the idea that there are accept, restriction, generation and transformation relationship among the lung, kidney and liver yin, so he also always used Radix Glehniae (Beishashen), Radix Ophiopogonis (Maidong), Radix Rehmanniae Recens (Shengdihuang), and Radix Rehmanniae Preparata (Shudihuang) in his compound recipes. If the yin blood is insufficient, Semen Ziziphi Spinosae (Suanzaoren) should be added. In order to prepare a out way for phlegm-heat caused dy liver yin deficiency, a lubricative, Semen Trichosanthis (Gualouren) was always used and raw Semen Coicis Recens (Shengyiyiren) too. Sichuan Rhizoma Coptidis (Chuanhuanglian) can be used to clear fire-heat, and Fructus Meliae Toosendan (Chuanlianzi) for pain caused by fire-heat. PMID:17096983

  7. Clinical and radiographic maxillofacial features of pycnodysostosis.

    PubMed

    Alves, Nilton; Cantín, Mario

    2014-01-01

    The aim of this study was to review of the literature to determine the radiographic and clinical maxillofacial features of pycnodysostosis emphasizing the main aspects of interest to the dentist in order to make them fit for the proper treatment of this population. It is important to make the diagnosis as early as possible in order to plan the treatment more suitable to provide a better life's quality to the patients. The most frequent clinical maxillofacial features were: grooved palate, midfacial hypoplasia, mandibular hypoplasia and enamel hypoplasia. The most common radiographic maxillofacial features were: obtuse mandibular angle, frontal/parietal/occiptal bossing, open fontanels and sutures, multiple impacted teeth. The earlier diagnostic of pycnodysostosis has a fundamental role in general health of the patients. We consider that is very important that the dentist know recognize the radiographic and clinical maxillofacial features of pycnodysostosis, which allows correct treatment planning avoiding risks and ensuring better life's quality to the patients. PMID:24753741

  8. Update on Clinical Features and Brain Abnormalities in Neurogenetics Syndromes

    ERIC Educational Resources Information Center

    Jackowski, Andrea Parolin; Laureano, Maura Regina; Del'Aquilla, Marco Antonio; de Moura, Luciana Monteiro; Assuncao, Idaiane; Silva, Ivaldo; Schwartzman, Jose Salomao

    2011-01-01

    Neuroimaging methods represent a critical tool in efforts to join the study of the neurobiology of genes with the neurobiology of behaviour, and to understand the neurodevelopmental pathways that give rise to cognitive and behavioural impairments. This article reviews the clinical features and highlights studies with a focus on the relevant…

  9. A systematic review of familial Alzheimer's disease: Differences in presentation of clinical features among three mutated genes and potential ethnic differences.

    PubMed

    Shea, Yat-Fung; Chu, Leung-Wing; Chan, Angel On-Kei; Ha, Joyce; Li, Yan; Song, You-Qiang

    2016-02-01

    There are great diversities of clinical phenotypes among the various familial Alzheimer's disease (FAD) families. We aimed to systematically review all the previously reported cases of FAD and to perform comparisons between Asian and white patients. In this regard, we collected individual-level data from 658 pedigrees. We found that patients with presenilin 1 (PSEN1) mutations had the earliest age of onset (AOO; 43.3 ± 8.6 years, p < 0.001) and were more commonly affected by seizures, spastic paraparesis, myoclonus, and cerebellar signs (p < 0.001, p < 0.001, p = 0.003, and p = 0.002, respectively). Patients with PSEN2 mutations have a delayed AOO with longest disease duration and presented more frequently with disorientation (p = 0.03). Patients with amyloid precursor protein (APP) mutations presented more frequently with aggression (p = 0.02) and those with APP duplication presented more frequently with apraxia (p = 0.03). PSEN1 mutations before codon 200 had an earlier AOO than those having mutations after codon 200 (41.4 ± 8.0 years vs. 44.7 ± 8.7 years, p < 0.001). Because 42.9% of the mutations reported are novel, the mutation spectrum and clinical features in Asian FAD families could be different from that of whites. Asian patients with PSEN1 mutations presented more frequently with disorientation (p = 0.02) and personality change (p = 0.01) but less frequently with atypical clinical features. Asian patients with APP mutations presented less frequently with aphasia (p = 0.02). Thus, clinical features could be modified by underlying mutations, and Asian FAD patients may have different clinical features when compared with whites. PMID:26337232

  10. Clinical features, endoscopic polypectomy and STK11 gene mutation in a nine-month-old Peutz-Jeghers syndrome Chinese infant

    PubMed Central

    Huang, Zhi-Heng; Song, Zai; Zhang, Ping; Wu, Jie; Huang, Ying

    2016-01-01

    AIM: To investigate multiple polyps in a Chinese Peutz-Jeghers syndrome (PJS) infant. METHODS: A nine-month-old PJS infant was admitted to our hospital for recurrent prolapsed rectal polyps for one month. The clinical characteristics, a colonoscopic image, the pathological characteristics of the polyps and X-ray images of the intestinal perforation were obtained. Serine threonine-protein kinase 11 (STK11) gene analysis was also performed using a DNA sample from this infant. RESULTS: Here we describe the youngest known Chinese infant with PJS. Five polyps, including a giant polyp of approximately 4 cm × 2 cm in size, were removed from the infant’s intestine. Laparotomy was performed to repair a perforation caused by pneumoperitoneum. The pathological results showed that this child had PJS. Molecular analysis of the STK11 gene further revealed a novel frameshift mutation (c.64_65het_delAT) in exon 1 in this PJS infant. CONCLUSION: The appropriate treatment method for multiple polyps in an infant must be carefully considered. Our results also show that the STK11 gene mutation is the primary cause of PJS. PMID:27004004

  11. Polymorphism in the IL4R gene and clinical features are associated with glioma prognosis: Analyses of case-cohort studies.

    PubMed

    Jin, Tian Bo; Du, Shuli; Zhu, Xi Kai; Li, Gang; Ouyang, Yongri; He, Na; Zhang, Zhiying; Zhang, Yuan; Kang, Longli; Yuan, Dongya

    2016-08-01

    Inflammatory gene polymorphisms may be associated with glioma risk. The purpose of this study was to analyze effects of certain inflammatory gene and some clinical factors on patient survival.The clinical information of 269 glioma patients conceived operation from September 2010 to May 2014 to decide the 1-, 3-year survival rates according to follow-up results and analyze age, gender, the WHO classification, extent of surgical resection, radiotherapy and chemotherapy factors effects on prognosis. Survival distributions were estimated by using the Kaplan-Meier method and difference in the survival was tested using the log-rank test. To estimate the association between the IL4, IL13, IL10, IL4R SNPs, and PFS and OS in glioma, the HR and 95% CI were calculated by univariate Cox proportional hazards model. Multivariate Cox model were performed to compute adjusted HR and 95% CI. All data was analyzed with SPSS17.0 package. Extent of surgical resection, chemotherapy, and age are an important factor in glioma overall survival and progression-free survival overall. Extent of surgery and chemotherapy are important factors in astrocytoma overall survival. Univariate analysis showed that IL4R rs1801275 was significantly associated with overall survival of glioma and astrocytoma patients (P < 0.05). Multivariate Cox regression analysis showed that IL4R rs1801275 GG genotype could increase the death risk of glioma and astrocytoma patients (Glioma: hazard ratio [HR]: 4.897, 95% confidence limits [95% CI]: 1.962-12.222, P = 0.001; Astrocytoma: HR: 15.944, 95% CI: 4.019-63.253, P < 0.05).Our research results showed that extent of surgical resection, age, and chemotherapy affect the prognosis of glioma. The IL4R gene may affect the survival of glioma patients. PMID:27495027

  12. Topological features in cancer gene expression data.

    PubMed

    Lockwood, S; Krishnamoorthy, B

    2015-01-01

    We present a new method for exploring cancer gene expression data based on tools from algebraic topology. Our method selects a small relevant subset from tens of thousands of genes while simultaneously identifying nontrivial higher order topological features, i.e., holes, in the data. We first circumvent the problem of high dimensionality by dualizing the data, i.e., by studying genes as points in the sample space. Then we select a small subset of the genes as landmarks to construct topological structures that capture persistent, i.e., topologically significant, features of the data set in its first homology group. Furthermore, we demonstrate that many members of these loops have been implicated for cancer biogenesis in scientific literature. We illustrate our method on five different data sets belonging to brain, breast, leukemia, and ovarian cancers. PMID:25592573

  13. Noonan syndrome: introduction and basic clinical features.

    PubMed

    Rohrer, T

    2009-12-01

    Noonan syndrome (NS) is a fairly common (1 per 1,000-2,500 live births) autosomal dominantly inherited disorder and the most common syndromal cause of congenital heart disease after Down's syndrome. The clinical features vary with age, but typical signs of NS include characteristic facial features with hypertelorism, down-slanting palpebral fissures, low-set posteriorly rotated ears, chest and spinal deformities, short stature, specific heart defects, learning disabilities and mild mental retardation. This article gives a brief introduction to NS and its basic clinical features using the established and generally accepted NS scoring system based on family history and facial, cardiac, growth, chest wall and other criteria. Aspects discussed include the definition, epidemiology, etiology, diagnosis and genetics of NS, as well as growth, skeletal and gonadal anomalies, pubertal development, ophthalmic and cutaneous abnormalities and the incidence of cancer in patients with NS. PMID:20029230

  14. Melanoma: Clinical Features and Genomic Insights

    PubMed Central

    Hawryluk, Elena B.; Tsao, Hensin

    2014-01-01

    Recent efforts in genomic research have enabled the characterization of molecular mechanisms underlying many types of cancers, ushering novel approaches for diagnosis and therapeutics. Melanoma is a molecularly heterogeneous disease, as many genetic alterations have been identified and the clinical features can vary. Although discoveries of frequent mutations including BRAF have already made clinically significant impact on patient care, there is a growing body of literature suggesting a role for additional mutations, driver and passenger types, in disease pathophysiology. Although some mutations have been strongly associated with clinical phenotypes of melanomas (such as physical distribution or morphologic subtype), the function or implications of many of the recently identified mutations remains less clear. The phenotypic and clinical impact of genomic mutations in melanoma remains a promising opportunity for progress in the care of melanoma patients. PMID:25183853

  15. Clinical features of neuromyelitis optica in children

    PubMed Central

    Ness, Jayne; Krupp, Lauren; Waubant, Emmanuelle; Hunt, Tyler; Olsen, Cody S.; Rodriguez, Moses; Lotze, Tim; Gorman, Mark; Benson, Leslie; Belman, Anita; Weinstock-Guttman, Bianca; Aaen, Greg; Graves, Jennifer; Patterson, Marc; Rose, John W.; Casper, T. Charles

    2016-01-01

    Objective: To compare clinical features of pediatric neuromyelitis optica (NMO) to other pediatric demyelinating diseases. Methods: Review of a prospective multicenter database on children with demyelinating diseases. Case summaries documenting clinical and laboratory features were reviewed by an adjudication panel. Diagnoses were assigned in the following categories: multiple sclerosis (MS), acute disseminated encephalomyelitis, NMO, and recurrent demyelinating disease not otherwise specified. Results: Thirty-eight cases of NMO were identified by review panel, 97% of which met the revised International Panel on NMO Diagnosis NMO-SD 2014 criteria, but only 49% met 2006 Wingerchuk criteria. Serum or CSF NMO immunoglobulin G (IgG) was positive in 65% of NMO cases that were tested; however, some patients became seropositive more than 3 years after onset despite serial testing. No patient had positive CSF NMO IgG and negative serum NMO IgG in contemporaneous samples. Other than race (p = 0.02) and borderline findings for sex (p = 0.07), NMO IgG seropositive patients did not differ in demographic, clinical, or laboratory features from seronegatives. Visual, motor, and constitutional symptoms (including vomiting, fever, and seizures) were the most common presenting features of NMO. Initiation of disease-modifying treatment was delayed in NMO vs MS. Two years after onset, patients with NMO had higher attack rates, greater disability accrual measured by overall Expanded Disability Status Scale score, and visual scores than did patients with MS. Conclusion: The new criteria for NMO spectrum disorders apply well to the pediatric setting, and given significant delay in treatment of NMO compared to pediatric MS and worse short-term outcomes, it is imperative to apply these to improve access to treatment. PMID:26683648

  16. Skeletal Muscle Laminopathies: A Review of Clinical and Molecular Features.

    PubMed

    Maggi, Lorenzo; Carboni, Nicola; Bernasconi, Pia

    2016-01-01

    LMNA-related disorders are caused by mutations in the LMNA gene, which encodes for the nuclear envelope proteins, lamin A and C, via alternative splicing. Laminopathies are associated with a wide range of disease phenotypes, including neuromuscular, cardiac, metabolic disorders and premature aging syndromes. The most frequent diseases associated with mutations in the LMNA gene are characterized by skeletal and cardiac muscle involvement. This review will focus on genetics and clinical features of laminopathies affecting primarily skeletal muscle. Although only symptomatic treatment is available for these patients, many achievements have been made in clarifying the pathogenesis and improving the management of these diseases. PMID:27529282

  17. Clinical and electrodiagnostic features of sciatic neuropathies.

    PubMed

    Distad, B Jane; Weiss, Michael D

    2013-02-01

    Sciatic neuropathy is the second most common neuropathy of the lower extremity and a common cause of foot drop. This article reviews the anatomy, clinical features, pathophysiology, and electrodiagnostic assessment of sciatic neuropathies. There are multiple potential sites of pathology, determined in part by the mechanism of insult, including trauma, compression, masses, inflammation, and vascular lesions. Diagnosis is augmented by careful electrodiagnostic studies and imaging to help distinguish sciatic neuropathy from other sources of pathology. Electrodiagnostic studies may also help in assessing for early recovery and in determining prognosis. PMID:23177034

  18. Autoimmune uveitis: clinical, pathogenetic, and therapeutic features.

    PubMed

    Prete, Marcella; Dammacco, Rosanna; Fatone, Maria Celeste; Racanelli, Vito

    2016-05-01

    Autoimmune uveitis (AU), an inflammatory non-infectious process of the vascular layer of the eye, can lead to visual impairment and, in the absence of a timely diagnosis and suitable therapy, can even result in total blindness. The majority of AU cases are idiopathic, whereas fewer than 20 % are associated with systemic diseases. The clinical severity of AU depends on whether the anterior, intermediate, or posterior part of the uvea is involved and may range from almost asymptomatic to rapidly sight-threatening forms. Race, genetic background, and environmental factors can also influence the clinical picture. The pathogenetic mechanism of AU is still poorly defined, given its remarkable heterogeneity and the many discrepancies between experimental and human uveitis. Even so, the onset of AU is thought to be related to an aberrant T cell-mediated immune response, triggered by inflammation and directed against retinal or cross-reactive antigens. B cells may also play a role in uveal antigen presentation and in the subsequent activation of T cells. The management of AU remains a challenge for clinicians, especially because of the paucity of randomized clinical trials that have systematically evaluated the effectiveness of different drugs. In addition to topical treatment, several different therapeutic options are available, although a standardized regimen is thus far lacking. Current guidelines recommend corticosteroids as the first-line therapy for patients with active AU. Immunosuppressive drugs may be subsequently required to treat steroid-resistant AU and for steroid-sparing purposes. The recent introduction of biological agents, such as those targeting tumor necrosis factor-α, is expected to remarkably increase the percentages of responders and to prevent irreversible sight impairment. This paper reviews the clinical features of AU and its crucial pathogenetic targets in relation to the current therapeutic perspectives. Also, the largest clinical trials

  19. Surface osteosarcoma: Clinical features and therapeutic implications

    PubMed Central

    Nouri, H.; Ben Maitigue, M.; Abid, L.; Nouri, N.; Abdelkader, A.; Bouaziz, M.; Mestiri, M.

    2015-01-01

    Introduction Surface osteosarcoma are rare variant of osteosarcoma that include parosteal osteosarcoma, periosteal osteosarcoma and high grade surface osteosarcoma. These lesions have different clinical presentation and biological behavior compared to conventional osteosarcoma, and hence need to be managed differently. Goal The aim of this study is to analyze the clinico-pathological features and outcome of a series of surface osteosarcoma in an attempt to define the adequate treatment of this rare entity. Patient and method It is a retrospective and bicentric study of 18 surface osteosarcoma that were seen at the KASSAB’s Institute and SAHLOUL Hospital from 2006 to 2013. The authors reviewed the clinical and radiologic features, histologic sections, treatments, and outcomes in this group of patients. Results Seven patients were male (38.9%) and 11 were female (61.1%) with mean age of 25 years (range from 16 to 55 years). Eleven lesions were in the femur and 7 in the tibia. We identified 11 parosteal osteosarcoma (six of them were dedifferentiated), 3 periosteal osteosarcoma and 4 high grade surface osteosarcoma. Six patients had neoadjuvant chemotherapy and all lesions had surgical resection. Margins were wide in 15 cases and intra lesional in 3 cases. Histological response to chemotherapy was poor in all cases. The mean follow up was 34.5 months. Six patients (33.3%) presented local recurrence and 8 patients (44.4%) presented lung metastases. Six patients (33.3%) died from the disease after a mean follow up of 12 months (6–30 months); all of them had high grade lesions. Conclusion Histological grade of malignancy is the main point to assess in surface osteosarcoma since it determines treatment and prognosis. Low grade lesions should be treated by wide resection, while high grade lesions need more aggressive surgical approach associated to post operative chemotherapy. PMID:26730360

  20. Moyamoya Disease: Epidemiology, Clinical Features, and Diagnosis

    PubMed Central

    Kim, Jong S.

    2016-01-01

    Moyamoya disease (MMD) is a chronic, occlusive cerebrovascular disease characterized by progressive stenosis at the terminal portion of the internal carotid artery and an abnormal vascular network at the base of the brain. Although its etiology remains unknown, recent genetic studies identified RNF213 in the 17q25-ter region as an important susceptibility gene of MMD among East Asian populations. Possibly because of genetic differences, MMD is relatively common in people living in East Asian countries such as Korea and Japan, compared to those in the Western Hemisphere. The prevalence of MMD appears to be slightly lower among Chinese, compared to Koreans or Japanese. There are two peaks of incidence with different clinical presentations, at around 10 years and 30-40 years. The peak appears to occur later in women than men. In children, ischemic symptoms, especially transient ischemic attacks, are predominant. Intellectual decline, seizures, and involuntary movements are also more common in this age group. In contrast, adult patients present with intracranial hemorrhage more often than pediatric patients. In patients with MMD, intracerebral hemorrhage is more often accompanied by intraventricular hemorrhage than in patients with hypertensive intracerebral hemorrhage. These different age peaks and different clinical presentations in each age group are also observed in MMD patients in the USA. Catheter angiography is the diagnostic method of choice. Magnetic resonance (MR) angiography and computed tomographic angiography are noninvasive diagnostic methods. High-resolution vessel wall MR imaging also helps diagnose MMD by revealing concentric vessel wall narrowing with basal collaterals. PMID:26846755

  1. Clinical features of Bednar's aphthae in infants

    PubMed Central

    Nam, Seung-Woo; Ahn, Seol Hee; Shin, Son-Moon

    2016-01-01

    Purpose Although Bednar's aphthae are common and regress spontaneously, these lesions may lead to feeding intolerance and are often misdiagnosed, rendering examinations useless. This study sheds new light on the clinical features of Bednar's aphthae. Methods Sixteen neonates and infants were newly diagnosed with Bednar's aphthae via routine health check-ups in an outpatient clinic. Medical records were retrospectively reviewed, and the following parameters were analyzed; sex, gestational age, birth weight, mode of delivery, and perinatal problems. A physical examination was carried out during the next outpatient visit to examine the healing process and check for the existence of scars or complications. Results Initial presentation included changes in feeding habits (n=10), longer feeding time, reduced intake, and increased irritability. In 6 patients, Bednar's aphthae were discovered incidentally, without prior symptoms. Feeding posture and method of feeding are important causes of Bednar's aphthae. Eleven patients were fed in a horizontal position, whereas 5 patients were fed in a semiseated position. Fifteen patients were bottle-fed, whereas 1 patient was exclusively breastfed. After correcting the feeding position, the ulcerative lesions disappeared within 1 month of diagnosis. During the follow-up period, lesions did not recur in any of the patients. Conclusion This study suggests that Bednar's aphthae are caused by mechanical pressure. A diagnosis of Bednar's aphthae should be considered when lesions are found on the palate of infants and when symptoms seem to be feeding related. Proper education of parents can both treat Bednar's aphthae and easily prevent its recurrence. PMID:26893601

  2. Clinical and neurophysiological features of tick paralysis.

    PubMed

    Grattan-Smith, P J; Morris, J G; Johnston, H M; Yiannikas, C; Malik, R; Russell, R; Ouvrier, R A

    1997-11-01

    The clinical and neurophysiological findings in six Australian children with generalized tick paralysis are described. Paralysis is usually caused by the mature female of the species Ixodes holocyclus. It most frequently occurs in the spring and summer months but can be seen at any time of year. Children aged 1-5 years are most commonly affected. The tick is usually found in the scalp, often behind the ear. The typical presentation is a prodrome followed by the development of an unsteady gait, and then ascending, symmetrical, flaccid paralysis. Early cranial nerve involvement is a feature, particularly the presence of both internal and external ophthalmoplegia. In contrast to the experience with North American ticks, worsening of paralysis in the 24-48 h following tick removal is common and the child must be carefully observed over this period. Death from respiratory failure was relatively common in the first half of the century and tick paralysis remains a potentially fatal condition. Respiratory support may be required for > 1 week but full recovery occurs. This is slow with several weeks passing before the child can walk unaided. Anti-toxin has a role in the treatment of seriously ill children but there is a high incidence of acute allergy and serum sickness. Neurophysiological studies reveal low-amplitude compound muscle action potentials with normal motor conduction velocities, normal sensory studies and normal response to repetitive stimulation. The biochemical structure of the toxin of I. holocyclus has not been fully characterized but there are many clinical, neurophysiological and experimental similarities to botulinum toxin. PMID:9397015

  3. Familial fatal insomnia with atypical clinical features in a patient with D178N mutation and homozygosity for Met at codon 129 of the prion protein gene

    PubMed Central

    Sun, Lin; Li, Xia; Lin, Xiang; Yan, Feng; Chen, Kathryn; Xiao, Shifu

    2015-01-01

    ABSTRACT. Familial fatal insomnia (FFI) is fatal disorder characterized by damage to select thalamic nuclei, together with progressive insomnia and dysautonomia. In subjects carrying the D178N prion protein (PRNP) mutation, distinct phenotypes can be observed, depending on the methionine (Met) /valine (Val) codon 129 polymorphism. We report here a Chinese case of FFI with a D178N/Met129 genotype of the PRNP gene, who exhibited rapidly progressive dementia combined with behavioral disturbances and paroxysmal limb myoclonus. Our patient did not show refractory insomnia early in the disease course, nor demonstrate typical MRI and EEG alterations. There was remarkable family history of similar symptoms. PMID:26074146

  4. [Narcolepsy: etiology, clinical features, diagnosis and treatment].

    PubMed

    Zawilska, Jolanta B; Woldan-Tambor, Agata; Płocka, Anna; Kużajska, Katarzyna; Wojcieszak, Jakub

    2012-01-01

     Narcolepsy is a chronic hypersomnia characterized by excessive daytime sleepiness (EDS) and manifestations of disrupted rapid eye movement sleep stage (cataplexy, sleep paralysis, and hypnagogic/hypnopompic hallucinations). Mechanisms underlying narcolepsy are not fully understood. Experimental data indicate that the disease is caused by a loss of hypocretin neurons in the hypothalamus, likely due to an autoimmune process triggered by environmental factors in susceptible individuals. Most patients with narcolepsy and cataplexy have very low hypocretin-1 levels in the cerebrospinal fluid. An appropriate clinical history, polysomnogram, and multiple sleep latency test are necessary for diagnosis of the disease. Additionally, two biological markers, i.e., cerebrospinal fluid hypocretin-1 levels and expression of the DQB1*0602 gene, are used. The treatment of narcolepsy is aimed at the different symptoms that the patient manifests. Excessive daytime sleepiness is treated with psychostimulants (amphetamine-like, modafinil and armodafinil). Cataplexy is treated with sodium oxybate (GHB), tricyclic antidepressants, or selective serotonin and noradrenaline reuptake inhibitors. Sleep paralysis, hallucinations, and fragmented sleep may be treated with sodium oxybate. Patients with narcolepsy should follow proper sleep hygiene and avoid strong emotions. PMID:23175331

  5. Urgent discectomy: Clinical features and neurological outcome

    PubMed Central

    Albert, Ruth; Lange, Max; Brawanski, Alexander; Schebesch, Karl-Michael

    2016-01-01

    Background: To evaluate the clinical features and outcome of patients with progressive neurological deficits due to disc herniation who were treated surgically within 24 h. Methods: We conducted a retrospective analysis of consecutive patients who were admitted between 2004 and 2013 via the Emergency Department. Records were screened for presenting symptoms, neurological status at admission, discharge, and 6-week follow-up. Results: About 72 of 526 patients underwent surgery within 24 h. Magnetic resonance imaging showed lumbar disc herniation in 72 patients. The most common presenting symptoms included radiculopathy (n = 69), the Lasègue sign (n = 60), sensory deficits (n = 57), or motor deficits (n = 47). In addition, 11 patients experienced perineal numbness and 12 had bowel and bladder dysfunction. At discharge, motor and sensory deficits and bowel and bladder dysfunction had improved significantly (P < 0.001, P = 0.029, and P = 0.015, respectively). Conclusion: Motor deficits, sensory deficits, and cauda equina dysfunction were significantly improved immediately after urgent surgery. After 6 weeks, motor and sensory deficits were also significantly improved compared to the neurological status at discharge. Thus, we advocate immediate surgery of disc herniation in patients with acute onset of motor deficits, perineal numbness, or bladder or bowel dysfunction indicative of cauda equina syndrome. PMID:26958423

  6. Polymorphisms in the 18S rDNA gene of Cystoisospora belli and clinical features of cystoisosporosis in HIV-infected patients.

    PubMed

    Resende, Deisy V; Pedrosa, André L; Correia, Dalmo; Cabrine-Santos, Marlene; Lages-Silva, Eliane; Meira, Wendell S F; Oliveira-Silva, Márcia B

    2011-03-01

    Intraspecific variability among Cystoisospora belli isolates and its clinical implications in human cystoisosporosis have not been established. In this study, the restriction fragment length polymorphisms in a 1.8-kb amplicon of the small subunit ribosomal DNA (SSU rDNA) of the parasite was investigated in 20 C. belli-positive stool samples obtained from 15 HIV-infected patients. Diarrheic syndrome was observed in all patients with cystoisosporosis and the number of diarrheic episodes per patient during hospitalization ranged from 1 to 26 (mean of 9.64 ± 9.30), with a mean duration of 2 to 12 days (mean of 5.90 ± 3 days). Three restriction profiles (RF) were generated with MboII digestion, which were named RFI, RFII, and RFIII. Two isolates obtained from a patient with extraintestinal cystoisosporosis showed distinct restriction profiles with MboII. This study demonstrates that patients can be infected with different C. belli genotypes, and this information may be useful for identifying new C. belli genotypes infecting humans. PMID:20967461

  7. Clinical, cellular, and molecular features of an Israeli xeroderma pigmentosum family with a frameshift mutation in the XPC gene: sun protection prolongs life.

    PubMed

    Slor, H; Batko, S; Khan, S G; Sobe, T; Emmert, S; Khadavi, A; Frumkin, A; Busch, D B; Albert, R B; Kraemer, K H

    2000-12-01

    An Ashkenazi Jewish Israeli family with two children affected with severe xeroderma pigmentosum was investigated. A son, XP12TA, developed skin cancer at 2 y and died at 10 y. A daughter, XP25TA, now 24 y old, was sun protected and began developing skin cancers at 10 y. Their cultured skin fibroblasts showed reductions in post-ultraviolet survival (11% of normal), unscheduled DNA synthesis (10% of normal), global genome DNA repair (15% of normal), and plasmid host cell reactivation (5% of normal). Transcription-coupled DNA repair was normal, however. Northern blot analysis revealed greatly reduced xeroderma pigmentosum complementation group C mRNA. A plasmid host cell reactivation assay assigned the cells to xeroderma pigmentosum complementation group C. Cells from both parents and an unaffected child exhibited normal post-ultraviolet-C survival and normal DNA repair. Sequencing the xeroderma pigmentosum complementation group C cDNA of XP12TA and XP25TA revealed a homozygous deletion of two bases (del AT 669-670) in exon 5 with a new termination site 10 codons downstream that is expected to encode a truncated xeroderma pigmentosum complementation group C protein. Sequence analysis of the xeroderma pigmentosum complementation group C cDNA in cells from the parents found identical heterozygous mutations: one allele carries both the exon 5 frameshift and an exon 15 polymorphism and the other allele carries neither alteration. Cells from the unaffected brother had two normal xeroderma pigmentosum complementation group C alleles. This frameshift mutation in the xeroderma pigmentosum complementation group C gene led to reduced DNA repair with multiple skin cancers and early death. Sun protection delayed the onset of skin cancer and prolonged life in a sibling with the same mutation. PMID:11121128

  8. Clinical and molecular features of Joubert syndrome and related disorders

    PubMed Central

    Parisi, Melissa A.

    2009-01-01

    Joubert syndrome (JBTS; OMIM 213300) is a rare, autosomal recessive disorder characterized by a specific congenital malformation of the hindbrain and a broad spectrum of other phenotypic findings that is now known to be caused by defects in the structure and/or function of the primary cilium. The complex hindbrain malformation that is characteristic of JBTS can be identified on axial magnetic resonance imaging and is known as the molar tooth sign (MTS); other diagnostic criteria include intellectual disability, hypotonia, and often, abnormal respiratory pattern and/or abnormal eye movements. In addition, a broad spectrum of other anomalies characterize Joubert syndrome and related disorders (JSRD), and may include retinal dystrophy, ocular coloboma, oral frenulae and tongue tumors, polydactyly, cystic renal disease (including cystic dysplasia or juvenile nephronophthisis), and congenital hepatic fibrosis. The clinical course can be variable, but most children with this condition survive infancy to reach adulthood. At least 8 genes cause JSRD, with some genotype-phenotype correlations emerging, including the association between mutations in the MKS3 gene and hepatic fibrosis characteristic of the JSRD subtype known as COACH syndrome. Several of the causative genes for JSRD are implicated in other ciliary disorders, such as juvenile nephronophthisis and Meckel syndrome, illustrating the close association between these conditions and their overlapping clinical features that reflect a shared etiology involving the primary cilium. PMID:19876931

  9. Clinical features of Friedreich's ataxia: classical and atypical phenotypes.

    PubMed

    Parkinson, Michael H; Boesch, Sylvia; Nachbauer, Wolfgang; Mariotti, Caterina; Giunti, Paola

    2013-08-01

    One hundred and fifty years since Nikolaus Friedreich's first description of the degenerative ataxic syndrome which bears his name, his description remains at the core of the classical clinical phenotype of gait and limb ataxia, poor balance and coordination, leg weakness, sensory loss, areflexia, impaired walking, dysarthria, dysphagia, eye movement abnormalities, scoliosis, foot deformities, cardiomyopathy and diabetes. Onset is typically around puberty with slow progression and shortened life-span often related to cardiac complications. Inheritance is autosomal recessive with the vast majority of cases showing an unstable intronic GAA expansion in both alleles of the frataxin gene on chromosome 9q13. A small number of cases are caused by a compound heterozygous expansion with a point mutation or deletion. Understanding of the underlying molecular biology has enabled identification of atypical phenotypes with late onset, or atypical features such as retained reflexes. Late-onset cases tend to have slower progression and are associated with smaller GAA expansions. Early-onset cases tend to have more rapid progression and a higher frequency of non-neurological features such as diabetes, cardiomyopathy, scoliosis and pes cavus. Compound heterozygotes, including those with large deletions, often have atypical features. In this paper, we review the classical and atypical clinical phenotypes of Friedreich's ataxia. PMID:23859346

  10. Exploring the relationship between fractal features and bacterial essential genes

    NASA Astrophysics Data System (ADS)

    Yong-Ming, Yu; Li-Cai, Yang; Qian, Zhou; Lu-Lu, Zhao; Zhi-Ping, Liu

    2016-06-01

    Essential genes are indispensable for the survival of an organism in optimal conditions. Rapid and accurate identifications of new essential genes are of great theoretical and practical significance. Exploring features with predictive power is fundamental for this. Here, we calculate six fractal features from primary gene and protein sequences and then explore their relationship with gene essentiality by statistical analysis and machine learning-based methods. The models are applied to all the currently available identified genes in 27 bacteria from the database of essential genes (DEG). It is found that the fractal features of essential genes generally differ from those of non-essential genes. The fractal features are used to ascertain the parameters of two machine learning classifiers: Naïve Bayes and Random Forest. The area under the curve (AUC) of both classifiers show that each fractal feature is satisfactorily discriminative between essential genes and non-essential genes individually. And, although significant correlations exist among fractal features, gene essentiality can also be reliably predicted by various combinations of them. Thus, the fractal features analyzed in our study can be used not only to construct a good essentiality classifier alone, but also to be significant contributors for computational tools identifying essential genes. Project supported by the Shandong Provincial Natural Science Foundation, China (Grant No. ZR2014FM022).

  11. Classification, clinical features, and genetics of neural tube defects

    PubMed Central

    Salih, Mustafa A.; Murshid, Waleed R.; Seidahmed, Mohammed Z.

    2014-01-01

    Neural tube defects (NTDs) constitute a major health burden (0.5-2/1000 pregnancies worldwide), and remain a preventable cause of still birth, neonatal, and infant death, or significant lifelong handicaps. The malformations result from failure of the neural folds to fuse in the midline, and form the neural tube between the third and the fourth week of embryonic development. This review article discusses their classification, clinical features, and genetics. Most NTDs are sporadic and both genetic, and non-genetic environmental factors are involved in its etiology. Consanguinity was suggested to contribute to the high incidence of NTDs in several countries, including Saudi Arabia. Syndromes, often associated with chromosomal anomalies, account for <10% of all NTDs; but a higher proportion (20%) has been documented in Saudi Arabia. Genetic predisposition constitutes the major underlying risk factor, with a strong implication of genes that regulate folate one-carbon metabolism and planar cell polarity. PMID:25551113

  12. Clinical features of measles in immunocompromised children.

    PubMed

    Nakano, T; Shimono, Y; Sugiyama, K; Nishihara, H; Higashigawa, M; Komada, Y; Ito, M; Sakurai, M; Yoshida, A; Kitamura, K; Ihara, T; Kamiya, H; Hamazaki, M; Sata, T

    1996-06-01

    Measles is often fatal for immunocompromised hosts. Protective immunity against measles has been studied but is still not completely understood. Recently, five cases of measles were encountered in immunocompromised children. Two of these were allogeneic bone marrow transplanted cases (one common variable immunodeficiency and one severe aplastic anemia) in remission, one Wilms' tumor case in remission, one hepatoblastoma case after cytotoxic therapy at disease onset and one exaggerating hemophagocytic syndrome case with suppressed natural killer cell activity. Clinical symptoms, laboratory findings and the immunologic backgrounds of these five patients were investigated. One of the patients, an 8 year old boy with hemophagocytic syndrome, died of giant cell pneumonia which was confirmed in the section of necropsy lung specimen. Two other patients who received allogeneic bone marrow transplants were not immune to measles, despite their own and their donors' immunizations. Their clinical symptoms were rather severe but both patients recovered and have remained seropositive for as long as 13 months. This fatality from measles is the first reported in a patient with hemophagocytic syndrome. Suppressed natural killer cell activity may be a poor prognostic factor. Also, secondary immunization failure for measles can occur in bone marrow transplanted patients with rather severe clinical symptoms. PMID:8741308

  13. Metabolic myopathies: clinical features and diagnostic approach.

    PubMed

    Smith, Edward C; El-Gharbawy, Areeg; Koeberl, Dwight D

    2011-05-01

    The rheumatologist is frequently called on to evaluate patients with complaints of myalgia, muscle cramps, and fatigue. The evaluation of these patients presents a diagnostic challenge given the nonspecific and intermittent nature of their complaints, often leading to inappropriate diagnostic testing. When these symptoms are associated with physical exertion, a metabolic myopathy should be suspected Although inflammatory myopathies may present with similar features, such a pattern should prompt a thorough evaluation for an underlying metabolic myopathy. This review discusses the most common causes of metabolic myopathies and reviews the current diagnostic options available to the clinician. PMID:21444020

  14. Cortical auditory disorders: clinical and psychoacoustic features.

    PubMed Central

    Mendez, M F; Geehan, G R

    1988-01-01

    The symptoms of two patients with bilateral cortical auditory lesions evolved from cortical deafness to other auditory syndromes: generalised auditory agnosia, amusia and/or pure word deafness, and a residual impairment of temporal sequencing. On investigation, both had dysacusis, absent middle latency evoked responses, acoustic errors in sound recognition and matching, inconsistent auditory behaviours, and similarly disturbed psychoacoustic discrimination tasks. These findings indicate that the different clinical syndromes caused by cortical auditory lesions form a spectrum of related auditory processing disorders. Differences between syndromes may depend on the degree of involvement of a primary cortical processing system, the more diffuse accessory system, and possibly the efferent auditory system. Images PMID:2450968

  15. Benign Occipital Epilepsies of Childhood: Clinical Features and Genetics

    ERIC Educational Resources Information Center

    Taylor, Isabella; Berkovic, Samuel F.; Kivity, Sara; Scheffer, Ingrid E.

    2008-01-01

    The early and late benign occipital epilepsies of childhood (BOEC) are described as two discrete electro-clinical syndromes, eponymously known as Panayiotopoulos and Gastaut syndromes. Our aim was to explore the clinical features, classification and clinical genetics of these syndromes using twin and multiplex family studies to determine whether…

  16. [Lung sarcoidosis: Clinical features and therapeutic issues].

    PubMed

    Uzunhan, Y; Jeny, F; Crockett, F; Piver, D; Kambouchner, M; Valeyre, D; Nunes, H

    2016-09-01

    Sarcoidosis is a granulomatous disease of unknown cause. This proteiform disease is characterized by an almost constant and often predominant lung involvement. The natural history of disease is difficult to predict at presentation. Diagnosis is based on a compatible clinical and radiological presentation and evidence of non-caseating granulomas. Exclusion of alternative diseases is also required according to clinical presentation. Biopsy samples of superficial lesions should be considered before other sites like per-endoscopic bronchial biopsies or endobronchial ultrasound-guided transbronchial needle aspiration. Therapeutic strategy for lung disease has to take into account the possible spontaneous resolution observed in newly diagnosed patients. Corticosteroids are the first choice when a treatment is decided, which concerns half of patients. Second and third line therapy are based respectively on immunosuppressive drugs and anti-TNFα drugs. Sarcoidosis mortality and morbidity are mainly linked to advanced pulmonary sarcoidosis - lung fibrosis, pulmonary hypertension, bronchial stenosis and chronic pulmonary aspergillosis. "Non anti-inflammatory" treatments have to be considered as well. Clinicians have an essential role in treatment indication, end-point targets and evaluation of response to treatment during follow-up and in finding the best benefice to risk balance. Progress made on pharmacogenetics may offer more personalized treatments for the patients. PMID:26897112

  17. Punctate follicular porokeratosis: clinical and pathologic features.

    PubMed

    Trikha, Ritika; Wile, Anna; King, Joy; Ward, Kimberley H M; Brodell, Robert T

    2015-11-01

    Porokeratosis is a disorder of keratinization characterized by an abnormal cornoid lamella surrounding an annular, scaly plaque with an atrophic center. A histologic variant of this condition has been proposed, termed follicular porokeratosis, in cases where follicular involvement was contiguous with an annular cornoid lamella. There has been only 1 report of punctate follicular porokeratosis, in which cornoid lamellae originated exclusively from hair follicles with no associated annular plaque. The authors present the second case of punctate follicular porokeratosis, further supporting the contention that this entity is a unique form of porokeratosis rather than a histologic variant. A 56-year-old African American female presented to the dermatology clinic with a 3-month history of keratotic lesions localized on the right posterior shoulder. Examination revealed an area of perifollicular keratotic papules, each surrounded by an erythematous rim. Histopathology revealed a cornoid lamella originating within a hair follicle, with the parakeratotic column protruding through the follicular orifice. The static nature of the condition along with exclusive involvement of hair follicles supports the notion of punctate follicular porokeratosis as a distinct clinical entity. The diagnosis of this condition relies heavily on proper histopathologic sampling revealing punctate follicular cornoid lamellae. PMID:26485244

  18. Functional foods: salient features and clinical applications.

    PubMed

    Riezzo, Giuseppe; Chiloiro, Marisa; Russo, Francesco

    2005-09-01

    The term "functional food" refers to foods or ingredients of foods providing an additional physiological benefit beyond their basic nutritional needs. Health benefits are best obtained through a varied diet containing fruits, vegetables, grains, legumes and seeds. However, fortified foods and dietary supplements have been marketed and food industry have made functional food one of their current leading trends. Recently, the number of functional foods that have a potential benefit on health has hugely grown and scientific evidence is supporting the role of functional foods in prevention and treatment of several diseases. Cancer, diabetes, heart disease and hypertension are the most important diseases that can be treated or prevented by functional foods; other diseases are osteoporosis, abnormal bowel motility, and arthritis. It has been estimated that 80% of cancer in USA have a nutrition/diet component suggesting a great impact of functional food and foods components on incidence and treatment of cancer. Numerous factors complicate the evaluation of scientific evidence such as the complexity of food substance, effect on food, metabolic changes associated to dietary changes, the lack of biological markers of disease development. This paper reviews the scientific evidence supporting this area regarding only those foods and ingredients in which a clear experimental and clinical evidence exists for their chemopreventive and therapeutic effects. PMID:16178793

  19. Primary ciliary dyskinesia: cytological and clinical features.

    PubMed

    Greenstone, M; Rutman, A; Dewar, A; Mackay, I; Cole, P J

    1988-05-01

    Thirty patients with functional and/or morphological abnormalities of respiratory tract cilia were identified. The diagnosis of primary ciliary dyskinesia was based on observed abnormalities of ciliary ultrastructure or beating in vitro (beat pattern, beat frequency or percentage of motile cilia). Beat frequency and motility indices approached the normal range in some cases and suggests that the term 'immotile cilia syndrome' is not appropriate. Morphological abnormalities were most commonly due to deficiency of dynein arms, affecting the outer arms (n = 7), inner arms (n = 3) or both (n = 10). Examples of radial spoke and microtubular defects were also identified but in seven subjects ciliary ultrastructure was normal. In six patients paired samples of nasal and bronchial cilia were obtained and showed consistent abnormalities of motility and ultrastructure. Adenosine triphosphate and adenosine triphosphatase did not restore in vitro motility when added to dynein deficient cilia. The clinical picture was of life-long sinusitis and recurrent bronchial infection but the spectrum was broader than that encompassed by Kartagener's triad (dextrocardia, sinusitis and bronchiectasis). Fourteen patients had normal cardiac situs and definite or highly suggestive evidence of bronchiectasis was present in only 17 patients. Radiological evidence of sinusitis was common but absence of frontal sinuses was not universal. Chronic serous otitis media was a frequent finding but deafness was rarely profound. Fertility problems were common but were not universal in female subjects. Lung function testing revealed evidence of airflow obstruction but this was mild in most cases. PMID:2975807

  20. Clinical features and pathophysiology of belching disorders

    PubMed Central

    Sun, Xiaomin; Ke, Meiyun; Wang, Zhifeng

    2015-01-01

    The symptomatic characteristics and psychosocial factors of belching were analyzed through questionnaire, and the pathophysiology of belch was studied with the combined methods of high-resolution manometry and impedance (HRM-IMP). 21 consecutively-enrolled patients with repeated belching, were conducted a questionnaire survey, and the data were analyzed with Pearson correlation analysis and exact propability method. 10 patients were performed HRM-IMP. 20 patients met the diagnostic criteria of belch, among who 17 cases had overlapped symptoms, and the functional dyspepsia was the most common, followed by gastroesophageal reflux disease; 16 patients experienced mental stimulation or negative events; 12 cases existed anxiety and (or) depression; 8 cases had neurotic personality. The number of the overlapped symptoms was associated with the anxiety status, while the belch severity had nothing to do with the anxiety/depression status. Among the 10 patients who accepted HRM-IMP, 9 existed the esophageal motility dysfunction, and 9 had supra-gastric belching. Belch had a variety of clinical manifestations, related to the mood changes and the environmental stress, and normally was combined with the abnormalities of psychology and personality traits. The belch patients normally experienced the esophageal motility disorders, among which the typical pattern was supra-gastric belching. PMID:26885161

  1. Clinical features and pathophysiology of belching disorders.

    PubMed

    Sun, Xiaomin; Ke, Meiyun; Wang, Zhifeng

    2015-01-01

    The symptomatic characteristics and psychosocial factors of belching were analyzed through questionnaire, and the pathophysiology of belch was studied with the combined methods of high-resolution manometry and impedance (HRM-IMP). 21 consecutively-enrolled patients with repeated belching, were conducted a questionnaire survey, and the data were analyzed with Pearson correlation analysis and exact propability method. 10 patients were performed HRM-IMP. 20 patients met the diagnostic criteria of belch, among who 17 cases had overlapped symptoms, and the functional dyspepsia was the most common, followed by gastroesophageal reflux disease; 16 patients experienced mental stimulation or negative events; 12 cases existed anxiety and (or) depression; 8 cases had neurotic personality. The number of the overlapped symptoms was associated with the anxiety status, while the belch severity had nothing to do with the anxiety/depression status. Among the 10 patients who accepted HRM-IMP, 9 existed the esophageal motility dysfunction, and 9 had supra-gastric belching. Belch had a variety of clinical manifestations, related to the mood changes and the environmental stress, and normally was combined with the abnormalities of psychology and personality traits. The belch patients normally experienced the esophageal motility disorders, among which the typical pattern was supra-gastric belching. PMID:26885161

  2. Pediatric multiple sclerosis: Clinical features and outcome.

    PubMed

    Waldman, Amy; Ness, Jayne; Pohl, Daniela; Simone, Isabella Laura; Anlar, Banu; Amato, Maria Pia; Ghezzi, Angelo

    2016-08-30

    Multiple sclerosis (MS) in children manifests with a relapsing-remitting MS (RRMS) disease course. Acute relapses consist of new neurologic deficits persisting greater than 24 hours, in the absence of intercurrent illness, and occur with a higher frequency early in the disease as compared to adult-onset RRMS. Most pediatric patients with MS recover well from these early relapses, and cumulative physical disability is rare in the first 10 years of disease. Brainstem attacks, poor recovery from a single attack, and a higher frequency of attacks portend a greater likelihood of future disability. Although prospective pediatric-onset MS cohorts have been established in recent years, there remains very limited prospective data detailing the longer-term clinical outcome of pediatric-onset MS into adulthood. Whether the advent of MS therapies, and the largely off-label access to such therapies in pediatric MS, has improved prognosis is unknown. MS onset during the key formative academic years, concurrent with active cognitive maturation, is an important determinant of long-term outcome, and is discussed in detail in another article in this supplement. Finally, increasing recognition of pediatric MS worldwide, recent launch of phase III trials for new agents in the pediatric MS population, and the clear imperative to more fully appreciate health-related quality of life in pediatric MS through adulthood highlight the need for standardized, validated, and robust outcome measures. PMID:27572865

  3. Clinical features, epidemiology, and therapy of lymphangioleiomyomatosis

    PubMed Central

    Taveira-DaSilva, Angelo M; Moss, Joel

    2015-01-01

    Lymphangioleiomyomatosis (LAM) is a multisystem disease of women, characterized by proliferation of abnormal smooth muscle-like LAM cells, leading to the formation of lung cysts, fluid-filled cystic structures in the axial lymphatics (eg, lymphangioleiomyomas), and renal angiomyolipomas. LAM is caused by mutations of the TSC1 or TSC2 genes, which encode, respectively, hamartin and tuberin, two proteins with a major role in control of the mammalian target of rapamycin (mTOR) signaling pathway. LAM occurs sporadically or in association with tuberous sclerosis complex, an autosomal-dominant syndrome characterized by widespread hamartomatous lesions. LAM may present with progressive dyspnea, recurrent pneumothorax, or chylothorax. Pulmonary function tests show reduced flow rates (forced expiratory volume in the first second) and diffusion capacity. Exercise testing may reveal gas exchange abnormalities, ventilatory limitation, and hypoxemia. The severity and progression of disease may be assessed by lung histology scores, quantification of computed tomography, pulmonary function testing, 6-minute walk tests, cardiopulmonary exercise testing, and measurement of serum vascular endothelial growth factor D levels. Sirolimus and everolimus, two mTOR inhibitors, are effective in stabilizing lung function and reducing the size of chylous effusions, lymphangioleiomyo-mas, and angiomyolipomas. However, inhibition of mTOR complex 1 increases autophagy, possibly enhancing LAM cell survival. Inhibition of autophagy with hydroxychloroquine, in combination with sirolimus, has been proposed as a possible treatment for LAM. Deficiency of tuberin results in increased RhoA GTPase activity and cell survival, an effect that is mediated through mTOR complex 2 signaling. Because sirolimus and everolimus only affect the activity of mTOR complex 1, therapies targeting RhoA GTPases with simvastatin, which inhibits Rho GTPases and promotes apoptosis, are being investigated. As in the case of

  4. Clinical and molecular genetic features of ARC syndrome.

    PubMed

    Gissen, Paul; Tee, Louise; Johnson, Colin A; Genin, Emmanuelle; Caliebe, Almuth; Chitayat, David; Clericuzio, Carol; Denecke, Jonas; Di Rocco, Maja; Fischler, Björn; FitzPatrick, David; García-Cazorla, Angeles; Guyot, Delphine; Jacquemont, Sebastien; Koletzko, Sibylle; Leheup, Bruno; Mandel, Hanna; Sanseverino, Maria Teresa Vieira; Houwen, Roderick H J; McKiernan, Patrick J; Kelly, Deirdre A; Maher, Eamonn R

    2006-10-01

    Arthrogryposis, renal dysfunction and cholestasis (ARC) syndrome (MIM 208085) is an autosomal recessive multisystem disorder that may be associated with germline VPS33B mutations. VPS33B is involved in regulation of vesicular membrane fusion by interacting with SNARE proteins, and evidence of abnormal polarised membrane protein trafficking has been reported in ARC patients. We characterised clinical and molecular features of ARC syndrome in order to identify potential genotype-phenotype correlations. The clinical phenotype of 62 ARC syndrome patients was analysed. In addition to classical features described previously, all patients had severe failure to thrive, which was not adequately explained by the degree of liver disease and 10% had structural cardiac defects. Almost half of the patients who underwent diagnostic organ biopsy (7/16) developed life-threatening haemorrhage. We found that most patients (9/11) who suffered severe haemorrhage (7 post biopsy and 4 spontaneous) had normal platelet count and morphology. Germline VPS33B mutations were detected in 28/35 families (48/62 individuals) with ARC syndrome. Several mutations were restricted to specific ethnic groups. Thus p.Arg438X mutation was common in the UK Pakistani families and haplotyping was consistent with a founder mutation with the most recent common ancestor 900-1,000 years ago. Heterozygosity was found in the VPS33B locus in some cases of ARC providing the first evidence of a possible second ARC syndrome gene. In conclusion we state that molecular diagnosis is possible for most children in whom ARC syndrome is suspected and VPS33B mutation analysis should replace organ biopsy as a first line diagnostic test for ARC syndrome. PMID:16896922

  5. Mechanisms of Disease and Clinical Features of Mutations of the Gene for Mitofusin 2: An Important Cause of Hereditary Peripheral Neuropathy with Striking Clinical Variability in Children and Adults

    ERIC Educational Resources Information Center

    Ouvrier, Robert; Grew, Simon

    2010-01-01

    Mitofusin 2, a large transmembrane GTPase located in the outer mitochondrial membrane, promotes membrane fusion and is involved in the maintenance of the morphology of axonal mitochondria. Mutations of the gene encoding mitofusin 2 ("MFN2") have recently been identified as the cause of approximately one-third of dominantly inherited cases of the…

  6. [Clinical features of accessory parotid gland tumors].

    PubMed

    Iguchi, Hiroyoshi; Wada, Tadashi; Yamamoto, Hidefumi; Yamada, Kei; Matsushita, Naoki; Okamoto, Sachimi; Teranishi, Yuichi; Koda, Yuki; Kosugi, Yuki; Yamane, Hideo

    2013-12-01

    Accessory parotid gland tumors are relatively rare; hence, adequately detailed clinical analyses of these tumors are difficult to perform at a single institution. In this report, we describe the findings for 65 patients [29 men, 36 women; median age, 51 (9-81) years] with accessory parotid gland tumors, consisting of 4 cases documented by us and 61 cases previously reported by other Japanese authors. Approximately 50% of the patients were treated in an otolaryngology department, while the remaining patients were treated in plastic surgery, oral surgery, or dermatology departments. In 4 patients, the results of preoperative fine-needle aspiration cytology indicated that the tumor was benign; however, the postoperative histopathology results revealed malignant tumors. The frequencies of malignant and benign tumors were 44.6% (n = 29) and 55.4% (n = 36), respectively. Mucoepidermoid carcinoma and pleomorphic adenoma were the most frequent types of malignant and benign accessory parotid gland tumors, respectively. Among the various surgical methods that were used, such as direct cheek and intraoral incisions, a standard parotidectomy incision was the most preferred treatment approach for these tumors. Recently, an endoscopic approach has also been found to yield satisfactory results. An optimal approach should be selected after evaluating the advantages and disadvantages of these methods. No definite guidelines are available regarding the choice of elective neck dissection and postoperative radiation therapy for malignant accessory parotid gland tumors. Although tumor resection (plus elective neck dissection) and postoperative radiation therapy have been frequently performed for various kinds of malignant accessory parotid gland tumors to date, additional studies are needed regarding the criteria for selecting elective neck dissection and postoperative radiation therapy. Since the malignancy rate for accessory parotid gland tumors is higher than that for parotid gland

  7. Polymicrobial Infective Endocarditis: Clinical Features and Prognosis.

    PubMed

    García-Granja, Pablo Elpidio; López, Javier; Vilacosta, Isidre; Ortiz-Bautista, Carlos; Sevilla, Teresa; Olmos, Carmen; Sarriá, Cristina; Ferrera, Carlos; Gómez, Itziar; Román, José Alberto San

    2015-12-01

    To describe the profile of left-sided polymicrobial endocarditis (PE) and to compare it with monomicrobial endocarditis (ME).Among 1011 episodes of left-sided endocarditis consecutively diagnosed in 3 tertiary centers, between January 1, 1996 and December 31, 2014, 60 were polymicrobial (5.9%), 821 monomicrobial (81.7%), and in 123 no microorganism was detected (12.2%). Seven patients (0.7%) were excluded from the analysis because contamination of biologic tissue could not be discarded. The authors described the clinical, microbiologic, echocardiographic, and outcome of patients with PE and compared it with ME.Mean age was 64 years SD 16 years, 67% were men and 30% nosocomial. Diabetes mellitus (35%) were the most frequent comorbidities, fever (67%) and heart failure (43%) the most common symptoms at admission. Prosthetic valves (50%) were the most frequent infection location and coagulase-negative Staphylococci (48%) and enterococci (37%) the leading etiologies. The most repeated combination was coagulase-negative Staphylococci with enterococci (n = 9). Polymicrobial endocarditis appeared more frequently in patients with underlying disease (70% versus 56%, P = 0.036), mostly diabetics (35% versus 24%, P = 0.044) with previous cardiac surgery (15% versus 8% P = 0.049) and prosthetic valves (50% versus 37%, P = 0.038). Coagulase-negative Staphylococci, enterococci, Gram-negative bacilli, anaerobes, and fungi were more frequent in PE. No differences on age, sex, symptoms, need of surgery, and in-hospital mortality were detected.Polymicrobial endocarditis represents 5.9% of episodes of left-sided endocarditis in our series. Despite relevant demographic and microbiologic differences between PE and ME, short-term outcome is similar. PMID:26656328

  8. Clinical and genetic features of anoctaminopathy in Saudi Arabia

    PubMed Central

    Bohlega, Saeed; Monies, Dorothy M.; Abulaban, Ahmad A.; Murad, Hatem N.; Alhindi, Hindi N.; Meyer, Brian F.

    2015-01-01

    Objectives: Characterization of the phenotypic, pathological, radiological, and genetic findings in 2 Saudi Arabian families with anoctaminopathies, and limb girdle muscular dystrophy type 2L (LGMD2L). Methods: Over a 2-year period from December 2010 to January 2013, the clinical presentations were analyzed and all genes responsible for limb girdle muscular dystrophy (LGMD) were screened in families seen at King Faisal Specialist Hospital and Research Centre, a tertiary care hospital in Riyadh, Saudi Arabia. Out of 66 families with LGMD, we identified 2 families (3.1%) with anoctaminopathy, ANO5 muscular dystrophy. Results: In the first case, a man presented with asymmetrical calves’ muscles weakness and atrophy, which was first noted at age 39. The creatinine kinase (CK) level was >20x normal, muscle biopsy showed necrotizing myopathic changes, and an MRI of the legs showed fatty-tissue replacement to muscle tissue with volume loss involving the gastrocnemius and soleus muscles in an asymmetrical fashion. Minimal disease progression was noted over 18 years of follow up. Exercise induced recurrent rhabdomyolysis was noted over the last 2 years. A novel ANO5 gene mutation (Arg58Trp) was found. In the second family, a male presented at the age of 41 with asymptomatic hyperCkemia and intermittent dyspnea. Over 10 years follow up, he became disabled with muscle cramps, rhabdomyolysis, myoglobinurea, and difficulty ambulating. Muscle biopsy showed necrotizing myopathy and perivascular and interstitial amyloid deposit in skeletal muscle. A homozygous deletion of 11.9 Kb encompassing exon 13 to exon 17 was found in the ANO5 gene. Full cardiac investigations were normal in both patients. Conclusion: The prevalence of LGMD2L is approximately 3.1% in a Saudi Arabian native LGMD cohort. Slowly progressive, late onset, and asymmetrical weakness was the salient features in these 2 families. The genetic findings were novel and will add to the spectrum of ANO5 known mutations

  9. Clinical features and pathobiology of Ebolavirus infection.

    PubMed

    Ansari, Aftab A

    2014-12-01

    mechanisms in the body facilitates the ability of the virus to replicate in an uncontrolled fashion leading to the rapidity by which the virus can cause lethality. Various laboratories have been working on defining such mechanisms utilizing in vitro culture systems, a variety of animal models including inbred strains of normal and select gene knock out mice, guinea pigs and nonhuman primates that have led to a better understanding of the potential mechanisms involved. There have also been some major advances made in the identification of therapies from the very simple (major supportive type of therapy), to the identification of a number of highly effective chemotherapeutic agents, a variety of highly effective preventive (demonstrating 100% effectiveness in nonhuman primate models) recombinant formulations (adenovirus based, VSV-based, rabies virus based), therapeutic candidate vaccines (cocktail of monoclonal antibodies such as ZMAPP) and alternate approaches (RNAi-based such as TKM-Ebola and antisense based such as AVI-7537) that show great promise and at an unprecedented rate of discovery that speaks well for the scientific research community at large. PMID:25260583

  10. Graphical Features of Functional Genes in Human Protein Interaction Network.

    PubMed

    Wang, Pei; Chen, Yao; Lü, Jinhu; Wang, Qingyun; Yu, Xinghuo

    2016-06-01

    With the completion of the human genome project, it is feasible to investigate large-scale human protein interaction network (HPIN) with complex networks theory. Proteins are encoded by genes. Essential, viable, disease, conserved, housekeeping (HK) and tissue-enriched (TE) genes are functional genes, which are organized and functioned via interaction networks. Based on up-to-date data from various databases or literature, two large-scale HPINs and six subnetworks are constructed. We illustrate that the HPINs and most of the subnetworks are sparse, small-world, scale-free, disassortative and with hierarchical modularity. Among the six subnetworks, essential, disease and HK subnetworks are more densely connected than the others. Statistical analysis on the topological structures of the HPIN reveals that the lethal, the conserved, the HK and the TE genes are with hallmark graphical features. Receiver operating characteristic (ROC) curves indicate that the essential genes can be distinguished from the viable ones with accuracy as high as almost 70%. Closeness, semi-local and eigenvector centralities can distinguish the HK genes from the TE ones with accuracy around 82%. Furthermore, the Venn diagram, cluster dendgrams and classifications of disease genes reveal that some classes of disease genes are with hallmark graphical features, especially for cancer genes, HK disease genes and TE disease genes. The findings facilitate the identification of some functional genes via topological structures. The investigations shed some light on the characteristics of the compete interactome, which have potential implications in networked medicine and biological network control. PMID:26841412

  11. Visual Aggregate Analysis of Eligibility Features of Clinical Trials

    PubMed Central

    He, Zhe; Carini, Simona; Sim, Ida; Weng, Chunhua

    2015-01-01

    Objective To develop a method for profiling the collective populations targeted for recruitment by multiple clinical studies addressing the same medical condition using one eligibility feature each time. Methods Using a previously published database COMPACT as the backend, we designed a scalable method for visual aggregate analysis of clinical trial eligibility features. This method consists of four modules for eligibility feature frequency analysis, query builder, distribution analysis, and visualization, respectively. This method is capable of analyzing (1) frequently used qualitative and quantitative features for recruiting subjects for a selected medical condition, (2) distribution of study enrollment on consecutive value points or value intervals of each quantitative feature, and (3) distribution of studies on the boundary values, permissible value ranges, and value range widths of each feature. All analysis results were visualized using Google Charts API. Five recruited potential users assessed the usefulness of this method for identifying common patterns in any selected eligibility feature for clinical trial participant selection. Results We implemented this method as a Web-based analytical system called VITTA (Visual Analysis Tool of Clinical Study Target Populations). We illustrated the functionality of VITTA using two sample queries involving quantitative features BMI and HbA1c for conditions “hypertension” and “Type 2 diabetes”, respectively. The recruited potential users rated the user-perceived usefulness of VITTA with an average score of 86.4/100. Conclusions We contributed a novel aggregate analysis method to enable the interrogation of common patterns in quantitative eligibility criteria and the collective target populations of multiple related clinical studies. A larger-scale study is warranted to formally assess the usefulness of VITTA among clinical investigators and sponsors in various therapeutic areas. PMID:25615940

  12. Clinical features of 58 Japanese patients with mosaic neurofibromatosis 1.

    PubMed

    Tanito, Katsumi; Ota, Arihito; Kamide, Ryoichi; Nakagawa, Hidemi; Niimura, Michihito

    2014-08-01

    Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder caused by mutation in the NF1 tumor-suppressor gene, and may sometimes manifest in a mosaic form. "Segmental NF1" is generally assumed to be the result of somatic mosaicism for a NF1 mutation, and patients with mosaic NF1 have typical features of NF1 limited to specific body segments. The clinical features of 58 patients (42 females and 16 males; aged 1-69 years; mean age, 23.4 years) with mosaic NF1 seen at the Jikei University Hospital during 2004-2007 and at the Jikei University Daisan Hospital during 2007-2011, were retrospectively studied. Somatic or gonosomal mosaicism was not investigated. Patients were classified into four groups: (i) pigmentary changes (café-au-lait spots and freckling) only (n = 32); (ii) neurofibromas only (n = 5); (iii) neurofibromas and pigmentary changes (n = 13); and (iv) solitary plexiform neurofibromas (n = 8). The area of involvement was variable. The majority of patients were asymptomatic, except patients with plexiform neurofibromas who presented most commonly with pain or tenderness. Lisch nodules were rarely seen. Only four of our 58 patients (6.9%) had specific NF1 complications, including language delay (n = 1) and bone deformity (n = 3). Two patients were ascertained through their children with generalized NF1. Patients with mosaic NF1 are at low risk of developing disease-associated complications, except patients with plexiform neurofibromas. However, they need to be aware of the small risk of having a child with generalized NF1. PMID:25041723

  13. Getting arthritis gene therapy into the clinic

    PubMed Central

    Evans, Christopher H.; Ghivizzani, Steven C.; Robbins, Paul D.

    2012-01-01

    Gene transfer technologies enable the controlled, targeted and sustained expression of gene products at precise anatomical locations, such as the joint. In this way, they offer the potential for more-effective, less-expensive treatments of joint diseases with fewer extra-articular adverse effects. A large body of preclinical data confirms the utility of intra-articular gene therapy in animal models of rheumatoid arthritis and osteoarthritis. However, relatively few clinical trials have been conducted, only one of which has completed phase II. This article summarizes the status in 2010 of the clinical development of gene therapy for arthritis, identifies certain constraints to progress and suggests possible solutions. PMID:21135882

  14. Oral candidosis. Clinical, historical, and therapeutic features of 100 cases.

    PubMed

    Fotos, P G; Vincent, S D; Hellstein, J W

    1992-07-01

    Oral candidosis is an increasingly important disease that affects a significant percentage of the population. Traditionally known as an opportunistic pathogen, the broader clinical scope of oropharyngeal candidal infections is now being recognized. The clinical and historical features of 100 patients referred for diagnosis and management of candidosis have been reviewed. The age, gender, chief complaint, medical history, medications, and clinical findings have been noted. A wide range of clinical signs and symptoms, and the rationale behind the topical and systemic antifungal therapies provided to this patient population, are discussed. PMID:1508508

  15. Genetic and clinical features of primary torsion dystonia

    PubMed Central

    Ozelius, Laurie J.; Bressman, Susan B.

    2011-01-01

    Primary torsion dystonia (PTD) is defined as a syndrome in which dystonia is the only clinical sign (except for tremor), and there is no evidence of neuronal degeneration or an acquired cause by history or routine laboratory assessment. Seven different loci have been recognized for PTD but only two of the genes have been identified. In this review we will described the phenotypes associated with these loci and discuss the responsible gene. PMID:21168499

  16. Opercular malformations: clinical and MRI features in 11 children.

    PubMed

    Rolland, Y; Adamsbaum, C; Sellier, N; Robain, O; Ponsot, G; Kalifa, G

    1995-11-01

    Opercular malformations are rare and complex brain malformations for which only very fragmented neuropathological descriptions have been reported. They are related to an abnormal development of both sylvian fissure and frontoparietal operculum. We report a retrospective clinical and MRI study of 11 patients presenting with opercular malformations. A congenital pseudobulbar syndrome was observed in six cases, various motor disorders in seven cases, mental retardation in six cases and epilepsy in four cases. The purpose of this study is to evaluate the main features of opercular malformations in children and to try to characterise this entity on the basis of its clinical features and MRI pattern. PMID:8577527

  17. The pathogenesis of the clinical features of oral-facial-digital syndrome type I

    PubMed Central

    AlKattan, Wael M.; Al-Qattan, Mohammad M.; Bafaqeeh, Sameer A.

    2015-01-01

    Oral-facial-digital syndrome type I (OFDI) is an X-linked syndrome, which has several craniofacial and limb features; and hence, patients frequently present to craniofacial and plastic surgeons. Oral-facial-digital syndrome type I is caused by mutations in the CXORF5 gene. The gene product is one of the basal body proteins of a slim microtubule-based organelle called the “primary cilium”. Most of the clinical features of OFDI patients are related to dysfunctions of the primary cilium leading to abnormal Hedgehog signal transduction, depressed planar cell polarity pathway, and errors in cell cycle control. PMID:26593159

  18. Screening feature genes of astrocytoma using a combined method of microarray gene expression profiling and bioinformatics analysis

    PubMed Central

    Cai, Yong; Zhong, Xingming; Wang, Yiqi; Yang, Jianguo

    2015-01-01

    The aim of our study was to find feature genes associated with astrocytoma and correlative gene functions which can distinguish cancer tissue from adjacent non-tumor astrocyte tissues. Gene expression profile GSE15824 was downloaded from Gene Expression Omnibus database which included 8 astrocytoma tissues and 3 adjacent non-tumor astrocyte samples. The raw data were first transformed into probe-level data and the differentially expressed genes (DEGs) between tissues of patients with astrocytoma and normal specimen were identified using T-test in samr package of R. The Database for Annotation, Visualization and Integrated Discovery (DAVID) was applied to analyze the gene ontology (GO) enrichment on gene functions and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Finally, corresponding protein-protein interaction (PPI) networks of DEGs was constructed using the Cytoscape based on the data collected from STRING online datasets. A total of 3072 genes, including 1799 up-regulated genes and 1273 down-regulated genes, were filtered as DEGs, and we learnt that the DEGs including AQP4, PMP2, SRARCL1 and SLC1A2CAMs etc and that AQP4 was most significantly related to cell osmotic pressure. Three feature genes in KEGG pathway are highly enriched in cancer specimen while two genes are in the normal tissues. The discovery of featured genes significantly related to the regulation of cell osmotic pressure, has the potential to use in clinic for diagnosis of astrocytoma in future. In addition, it has a great significance on studying mechanism, distinguishing normal and cancer tissues, and exploring new treatments for astrocytoma. However, further experiments were needed to confirm our result. PMID:26770395

  19. Screening feature genes of astrocytoma using a combined method of microarray gene expression profiling and bioinformatics analysis.

    PubMed

    Cai, Yong; Zhong, Xingming; Wang, Yiqi; Yang, Jianguo

    2015-01-01

    The aim of our study was to find feature genes associated with astrocytoma and correlative gene functions which can distinguish cancer tissue from adjacent non-tumor astrocyte tissues. Gene expression profile GSE15824 was downloaded from Gene Expression Omnibus database which included 8 astrocytoma tissues and 3 adjacent non-tumor astrocyte samples. The raw data were first transformed into probe-level data and the differentially expressed genes (DEGs) between tissues of patients with astrocytoma and normal specimen were identified using T-test in samr package of R. The Database for Annotation, Visualization and Integrated Discovery (DAVID) was applied to analyze the gene ontology (GO) enrichment on gene functions and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Finally, corresponding protein-protein interaction (PPI) networks of DEGs was constructed using the Cytoscape based on the data collected from STRING online datasets. A total of 3072 genes, including 1799 up-regulated genes and 1273 down-regulated genes, were filtered as DEGs, and we learnt that the DEGs including AQP4, PMP2, SRARCL1 and SLC1A2CAMs etc and that AQP4 was most significantly related to cell osmotic pressure. Three feature genes in KEGG pathway are highly enriched in cancer specimen while two genes are in the normal tissues. The discovery of featured genes significantly related to the regulation of cell osmotic pressure, has the potential to use in clinic for diagnosis of astrocytoma in future. In addition, it has a great significance on studying mechanism, distinguishing normal and cancer tissues, and exploring new treatments for astrocytoma. However, further experiments were needed to confirm our result. PMID:26770395

  20. Clinical investigation of speech signal features among patients with schizophrenia

    PubMed Central

    ZHANG, Jing; PAN, Zhongde; GUI, Chao; CUI, Donghong

    2016-01-01

    Background A new area of interest in the search for biomarkers for schizophrenia is the study of the acoustic parameters of speech called 'speech signal features'. Several of these features have been shown to be related to emotional responsiveness, a characteristic that is notably restricted in patients with schizophrenia, particularly those with prominent negative symptoms. Aim Assess the relationship of selected acoustic parameters of speech to the severity of clinical symptoms in patients with chronic schizophrenia and compare these characteristics between patients and matched healthy controls. Methods Ten speech signal features-six prosody features, formant bandwidth and amplitude, and two spectral features-were assessed using 15-minute speech samples obtained by smartphone from 26 inpatients with chronic schizophrenia (at enrollment and 1 week later) and from 30 healthy controls (at enrollment only). Clinical symptoms of the patients were also assessed at baseline and 1 week later using the Positive and Negative Syndrome Scale, the Scale for the Assessment of Negative Symptoms, and the Clinical Global Impression-Schizophrenia scale. Results In the patient group the symptoms were stable over the 1-week interval and the 1-week test-retest reliability of the 10 speech features was good (intraclass correlation coefficients [ICC] ranging from 0.55 to 0.88). Comparison of the speech features between patients and controls found no significant differences in the six prosody features or in the formant bandwidth and amplitude features, but the two spectral features were different: the Mel-frequency cepstral coefficient (MFCC) scores were significantly lower in the patient group than in the control group, and the linear prediction coding (LPC) scores were significantly higher in the patient group than in the control group. Within the patient group, 10 of the 170 associations between the 10 speech features considered and the 17 clinical parameters considered were

  1. Using data mining to characterize DNA mutations by patient clinical features.

    PubMed Central

    Evans, S.; Lemon, S. J.; Deters, C.; Fusaro, R. M.; Durham, C.; Snyder, C.; Lynch, H. T.

    1997-01-01

    In most hereditary cancer syndromes, finding a correspondence between various genetic mutations within a gene (genotype) and a patient's clinical cancer history (phenotype) is challenging; to date there are few clinically meaningful correlations between specific DNA intragenic mutations and corresponding cancer types. To define possible genotype and phenotype correlations, we evaluated the application of data mining methodology whereby the clinical cancer histories of gene-mutation-positive patients were used to define valid or "true" patterns for a specific DNA intragenic mutation. The clinical histories of patients with their corresponding detailed attributes without the same oncologic intragenic mutation were labeled incorrect or "false" patterns. The results of data mining technology yielded characterizing rules for the true cases that constituted clinical features which predicted the intragenic mutation. Some of the initial results derived correlations already independently known in the literature, adding to the confidence of using this methodological approach. PMID:9357627

  2. Different morphologic aspects and clinical features in massive hepatic amyloidosis.

    PubMed

    Melato, M; Manconi, R; Magris, D; Morassi, P; Benussi, D G; Tiribelli, C

    1984-01-01

    4 cases of massive hepatic amyloidosis are reported with special reference to their clinical profiles and histologic features. On the basis of these data, two different clinical and histologic courses of the disease can be distinguished. 2 patients showed marked hepatomegaly without cholestasis, whereas in the other 2 the clinical picture was characterized by much less pronounced hepatomegaly, but by severe and progressive intrahepatic cholestasis. The time course of the disease seems to be different in the two forms, the cholestatic form being more rapidly fatal than the other. PMID:6745505

  3. Key Clinical Features to Identify Girls with "CDKL5" Mutations

    ERIC Educational Resources Information Center

    Bahi-Buisson, Nadia; Nectoux, Juliette; Rosas-Vargas, Haydee; Milh, Mathieu; Boddaert, Nathalie; Girard, Benoit; Cances, Claude; Ville, Dorothee; Afenjar, Alexandra; Rio, Marlene; Heron, Delphine; Morel, Marie Ange N'Guyen; Arzimanoglou, Alexis; Philippe, Christophe; Jonveaux, Philippe; Chelly, Jamel; Bienvenu, Thierry

    2008-01-01

    Mutations in the human X-linked cyclin-dependent kinase-like 5 ("CDKL5") gene have been shown to cause infantile spasms as well as Rett syndrome (RTT)-like phenotype. To date, less than 25 different mutations have been reported. So far, there are still little data on the key clinical diagnosis criteria and on the natural history of…

  4. Repetitive Behaviors in Autism: Relationships with Associated Clinical Features

    ERIC Educational Resources Information Center

    Gabriels, Robin L.; Cuccaro, Michael L.; Hill, Dina E.; Ivers, Bonnie J.; Goldson, Edward

    2005-01-01

    Relationships between repetitive behaviors (RBs) and associated clinical features (i.e., cognitive and adaptive functioning levels, sleep problems, medication use, and other behavioral problems) were examined in two groups (High nonverbal IQ greater than or equal to 97 versus Low nonverbal IQ less than or equal to 56) of children with autism…

  5. Zika virus: epidemiology, clinical features and host-virus interactions.

    PubMed

    Hamel, Rodolphe; Liégeois, Florian; Wichit, Sineewanlaya; Pompon, Julien; Diop, Fodé; Talignani, Loïc; Thomas, Frédéric; Desprès, Philippe; Yssel, Hans; Missé, Dorothée

    2016-01-01

    Very recently, Zika virus (ZIKV) has gained a medical importance following the large-scale epidemics in South Pacific and Latin America. This paper reviews information on the epidemiology and clinical features of Zika disease with a particular emphasis on the host-virus interactions that contribute to the pathogenicity of ZIKV in humans. PMID:27012221

  6. Diffuse Infiltrative Lesion of the Breast: Clinical and Radiologic Features

    PubMed Central

    An, Yeong Yi; Cha, Eun Suk; Kim, Hyeon Sook; Kang, Bong Joo; Park, Chang Suk; Jung, Na Young; Whang, In Yong; Yoon, Soo Kyung

    2011-01-01

    The purpose of this paper is to show the clinical and radiologic features of a variety of diffuse, infiltrative breast lesions, as well to review the relevant literature. Radiologists must be familiar with the various conditions that can diffusely involve the breast, including normal physiologic changes, benign disease and malignant neoplasm. PMID:21228947

  7. Pseudohypoaldosteronism type 1: clinical features and management in infancy

    PubMed Central

    Amin, N; Alvi, N S; Barth, J H; Field, H P; Finlay, E; Tyerman, K; Frazer, S; Savill, G; Wright, N P; Makaya, T; Mushtaq, T

    2013-01-01

    Summary Type 1 pseudohypoaldosteronism (PHA) is a rare heterogeneous group of disorders characterised by resistance to aldosterone action. There is resultant salt wasting in the neonatal period, with hyperkalaemia and metabolic acidosis. Only after results confirm isolated resistance to aldosterone can the diagnosis of type 1 PHA be confidently made. Type 1 PHA can be further classified into i) renal type 1 (autosomal dominant (AD)) and ii) multiple target organ defect/systemic type 1 (autosomal recessive (AR)). The aim of this case series was to characterise the mode of presentation, management and short-term clinical outcomes of patients with PHA type 1. Case notes of newly diagnosed infants presenting with PHA type 1 were reviewed over a 5-year time period. Seven patients were diagnosed with PHA type 1. Initial presentation ranged from 4 to 28 days of age. Six had weight loss as a presenting feature. All subjects had hyperkalaemia, hyponatraemia, with elevated renin and aldosterone levels. Five patients have renal PHA type 1 and two patients have systemic PHA type, of whom one has had genetic testing to confirm the AR gene mutation on the SCNN1A gene. Renal PHA type 1 responds well to salt supplementation, whereas management of patients with systemic PHA type 1 proves more difficult as they are likely to get frequent episodes of electrolyte imbalance requiring urgent correction. Learning points Patients with type 1 PHA are likely to present in the neonatal period with hyponatraemia, hyperkalaemia and metabolic acidosis and can be diagnosed by the significantly elevated plasma renin activity and aldosterone levels.The differential diagnosis of type 1 PHA includes adrenal disorders such as adrenal hypoplasia and congenital adrenal hyperplasia; thus, adrenal function including cortisol levels, 17-hydroxyprogesterone and a urinary steroid profile are required. Secondary (transient) causes of PHA may be due to urinary tract infections or renal anomalies; thus, urine

  8. Differences in clinical features of Crohn's disease and intestinal tuberculosis

    PubMed Central

    Huang, Xin; Liao, Wang-Di; Yu, Chen; Tu, Yi; Pan, Xiao-Lin; Chen, You-Xiang; Lv, Nong-Hua; Zhu, Xuan

    2015-01-01

    AIM: To investigate the clinical features of Crohn’s disease (CD) and intestinal tuberculosis (ITB) with a scoring system that we have developed. METHODS: A total of 25 CD and 40 ITB patients were prospectively enrolled from August 2011 to July 2012. Their characteristics and clinical features were recorded. Laboratory, endoscopic, histologic and radiographic features were determined. The features with a high specificity were selected to establish a scoring system. The features supporting CD scored +1, and those supporting ITB scored -1; each patient received a final total score. A receiver operating characteristic (ROC) curve was used to determine the best cut-off value for distinguishing CD from ITB. RESULTS: Based on a high specificity of differentiating between CD and ITB, 12 features, including longitudinal ulcers, nodular hyperplasia, cobblestone-like mucosa, intestinal diseases, intestinal fistula, the target sign, the comb sign, night sweats, the purified protein derivative test, the interferon-γ release assay (T-SPOT.TB), ring ulcers and ulcer scars, were selected for the scoring system. The results showed that the average total score of the CD group was 3.12 ± 1.740, the average total score of the ITB group was -2.58 ± 0.984, the best cutoff value for the ROC curve was -0.5, and the diagnostic area under the curve was 0.997, which was statistically significant (P < 0.001). The patients whose total scores were higher than -0.5 were diagnosed with CD; otherwise, patients were diagnosed with ITB. Overall, the diagnostic accuracy rate and misdiagnosis rate of this scoring system were 97% and 3%, respectively. CONCLUSION: Some clinical features are valuable for CD and ITB diagnosis. The described scoring system is key to differentiating between CD and ITB. PMID:25834333

  9. Demographic and clinical features of neuromyelitis optica: A review

    PubMed Central

    Asgari, N; Apiwattanakul, M; Palace, J; Paul, F; Leite, MI; Kleiter, I; Chitnis, T

    2015-01-01

    The comparative clinical and demographic features of neuromyelitis optica (NMO) are not well known. In this review we analyzed peer-reviewed publications for incidence and prevalence, clinical phenotypes, and demographic features of NMO. Population-based studies from Europe, South East and Southern Asia, the Caribbean, and Cuba suggest that the incidence and prevalence of NMO ranges from 0.05–0.4 and 0.52–4.4 per 100,000, respectively. Mean age at onset (32.6–45.7) and median time to first relapse (8–12 months) was similar. Most studies reported an excess of disease in women and a relapsing course, particularly in anti-aquaporin 4 antibody (anti AQP4-IgG)-positive patients. Ethnicity may have a bearing on disease phenotype and clinical outcome. Despite limitations inherent to the review process, themes noted in clinical and demographic features of NMO among different populations promote a more global understanding of NMO and strategies to address it. PMID:25921037

  10. A gene feature enumeration approach for describing HLA allele polymorphism.

    PubMed

    Mack, Steven J

    2015-12-01

    HLA genotyping via next generation sequencing (NGS) poses challenges for the use of HLA allele names to analyze and discuss sequence polymorphism. NGS will identify many new synonymous and non-coding HLA sequence variants. Allele names identify the types of nucleotide polymorphism that define an allele (non-synonymous, synonymous and non-coding changes), but do not describe how polymorphism is distributed among the individual features (the flanking untranslated regions, exons and introns) of a gene. Further, HLA alleles cannot be named in the absence of antigen-recognition domain (ARD) encoding exons. Here, a system for describing HLA polymorphism in terms of HLA gene features (GFs) is proposed. This system enumerates the unique nucleotide sequences for each GF in an HLA gene, and records these in a GF enumeration notation that allows both more granular dissection of allele-level HLA polymorphism and the discussion and analysis of GFs in the absence of ARD-encoding exon sequences. PMID:26416087

  11. Clinical and dermatoscopic features of porokeratosis palmaris et plantaris

    PubMed Central

    Udare, Satish; Hemmady, Karishma

    2016-01-01

    A dermatoscope is an important tool in a dermatologist's armamentarium as it can eliminate the need for a biopsy in a wide array of conditions. Porokeratosis was described by Mibelli and Respighi in 1893, as a disorder of keratinization which on the basis of distribution patterns was described as five clinical variants that portrayed a coronoid lamella on histopathology. We describe a case of asymptomatic, long-standing palmar and plantar pits, which on dermatoscopy showed features suggestive of porokeratosis, which was later reconfirmed by histopathologic sections. This report depicts diagnostic features of porokeratosis and obviates the need for invasive procedures for its diagnosis. PMID:27559506

  12. Clinical and dermatoscopic features of porokeratosis palmaris et plantaris.

    PubMed

    Udare, Satish; Hemmady, Karishma

    2016-01-01

    A dermatoscope is an important tool in a dermatologist's armamentarium as it can eliminate the need for a biopsy in a wide array of conditions. Porokeratosis was described by Mibelli and Respighi in 1893, as a disorder of keratinization which on the basis of distribution patterns was described as five clinical variants that portrayed a coronoid lamella on histopathology. We describe a case of asymptomatic, long-standing palmar and plantar pits, which on dermatoscopy showed features suggestive of porokeratosis, which was later reconfirmed by histopathologic sections. This report depicts diagnostic features of porokeratosis and obviates the need for invasive procedures for its diagnosis. PMID:27559506

  13. Dementia pugilistica with clinical features of Alzheimer's disease.

    PubMed

    Areza-Fegyveres, Renata; Rosemberg, Sergio; Castro, Rosa Maria R P S; Porto, Claudia Sellitto; Bahia, Valéria Santoro; Caramelli, Paulo; Nitrini, Ricardo

    2007-09-01

    A 61-year-old ex-boxer presented with a three-year history of progressive memory decline. During a seven-year follow-up period, there was a continuous cognitive decline, very similar to that usually observed in Alzheimer's disease. Parkinsonian, pyramidal or cerebellar signs were conspicuously absent. Neuropathological examination revealed the typical features of dementia pugilistica: cavum septi pellucidi with multiple fenestrations, numerous neurofibrillary tangles in the cerebral isocortex and hippocampus (and rare senile plaques). Immunohistochemistry disclosed a high number of tau protein deposits and scarce beta-amyloid staining. This case shows that dementia pugilistica may present with clinical features practically undistinguishable from Alzheimer's disease. PMID:17952290

  14. Confetti-like Sparing: A Diagnostic Clinical Feature of Melasma.

    PubMed

    Wu, Douglas C; Fitzpatrick, Richard E; Goldman, Mitchel P

    2016-02-01

    Diagnostic uncertainty when a patient presents with melasma-like Undings can lead to suboptimal treatment and inaccurate prognostic expectations. In this study, the authors present a unique clinical feature of melasma that they term the "Fitzpatrick macule" and test its Utility in establishing diagnostic certainty. The "Fitzpatrick macule" is a confetti-like macule of regularly pigmented skin located within a larger patch of melasma hyperpigmentation. To test its diagnostic Utility, the authors compared clinical photography of known cases of melasma with common mimickers, such as poikiloderma of Civatte and solar lentiginosis, and determined the positivity rate of the Fitzpatrick macule in each scenario. Their results show that 89.1 percent of clinical photographs of melasma were positive for the presence of Fitzpatrick macules compared to 1.1 percent that were negative. In contrast, 37.5 and 56.3 percent of clinical photographs of poikiloderma of Civatte were positive and negative for Fitzpatrick macules, respectively. Solar lentiginosis showed a 5.6 percent positivity and a 77.8 percent negativity for Fitzpatrick macules. The sensitivity and specificity of Fitzpatrick macules for melasma was 99 and 83 percent, respectively. In summary, the authors report a highly sensitive and specific clinical feature of melasma. In cases of diagnostic uncertainty, the presence of Fitzpatrick macules may aid in establishing a diagnosis of melasma. PMID:27047632

  15. Systems Medicine: from molecular features and models to the clinic in COPD

    PubMed Central

    2014-01-01

    Background and hypothesis Chronic Obstructive Pulmonary Disease (COPD) patients are characterized by heterogeneous clinical manifestations and patterns of disease progression. Two major factors that can be used to identify COPD subtypes are muscle dysfunction/wasting and co-morbidity patterns. We hypothesized that COPD heterogeneity is in part the result of complex interactions between several genes and pathways. We explored the possibility of using a Systems Medicine approach to identify such pathways, as well as to generate predictive computational models that may be used in clinic practice. Objective and method Our overarching goal is to generate clinically applicable predictive models that characterize COPD heterogeneity through a Systems Medicine approach. To this end we have developed a general framework, consisting of three steps/objectives: (1) feature identification, (2) model generation and statistical validation, and (3) application and validation of the predictive models in the clinical scenario. We used muscle dysfunction and co-morbidity as test cases for this framework. Results In the study of muscle wasting we identified relevant features (genes) by a network analysis and generated predictive models that integrate mechanistic and probabilistic models. This allowed us to characterize muscle wasting as a general de-regulation of pathway interactions. In the co-morbidity analysis we identified relevant features (genes/pathways) by the integration of gene-disease and disease-disease associations. We further present a detailed characterization of co-morbidities in COPD patients that was implemented into a predictive model. In both use cases we were able to achieve predictive modeling but we also identified several key challenges, the most pressing being the validation and implementation into actual clinical practice. Conclusions The results confirm the potential of the Systems Medicine approach to study complex diseases and generate clinically relevant

  16. Enteroviral encephalitis in children: clinical features, pathophysiology, and treatment advances

    PubMed Central

    Jain, Shikha; Patel, Bhupeswari; Bhatt, Girish Chandra

    2014-01-01

    Enteroviruses (EVs) have emerged as one of the important etiological agents as a causative organism for encephalitis, especially in children and adults. After the first report of EV encephalitis cases in 1950s, there have been increasing reports of regular outbreaks of EV encephalitis worldwide. Enteroviruses are RNA viruses of the family Picornaviridae that consists of more than 100 serotypes, which are characterized by a single positive-strand genomic RNA. The clinical features are pleomorphic and can be accompanied by mucocutaneous manifestations or isolated encephalitis only. The incidence of encephalitis in EV infection is reported to be about 3% and is associated with high mortality and morbidity. A number of newer therapeutic agents have been used in EV encephalitis with variable results. This review will focus on clinical features, pathophysiology, and newer treatment modality in EV encephalitis. PMID:25175874

  17. Clinical features and management of hereditary spastic paraplegia.

    PubMed

    Faber, Ingrid; Servelhere, Katiane R; Martinez, Alberto R M; D'Abreu, Anelyssa; Lopes-Cendes, Iscia; França-Jr, Marcondes C

    2014-03-01

    Hereditary spastic paraplegia (HSP) is a group of genetically-determined disorders characterized by progressive spasticity and weakness of lower limbs. An apparently sporadic case of adult-onset spastic paraplegia is a frequent clinical problem and a significant proportion of cases are likely to be of genetic origin. HSP is clinically divided into pure and complicated forms. The later present with a wide range of additional neurological and systemic features. To date, there are up to 60 genetic subtypes described. All modes of monogenic inheritance have been described: autosomal dominant, autosomal recessive, X-linked and mitochondrial traits. Recent advances point to abnormal axonal transport as a key mechanism leading to the degeneration of the long motor neuron axons in the central nervous system in HSP. In this review we aim to address recent advances in the field, placing emphasis on key diagnostic features that will help practicing neurologists to identify and manage these conditions. PMID:24676440

  18. Sensory symptoms in Parkinson's disease: Clinical features, pathophysiology, and treatment.

    PubMed

    Zhu, Mingxin; Li, Man; Ye, Dawei; Jiang, Wei; Lei, Ting; Shu, Kai

    2016-08-01

    Parkinson's disease (PD) is one of the most common forms of neurodegenerative disease in the elderly population and is typically manifested by motor symptoms and nonmotor symptoms and signs. Nonmotor symptoms, such as sensory symptoms, have been regarded as the significant features of this disease. These symptoms often occur in early stages of PD and influence quality of life. However, researchers suggest that the sensory symptoms of PD are frequently unrecognized by clinicians and remain untreated. The disorders include pain, olfactory disturbance, and visual dysfunction input on the underlying sensory abnormality. This Review focuses on the clinical features, pathophysiological mechanisms, and treatment strategies for sensory symptoms of PD from both clinical studies and basic research, providing a comprehensive overview of the sensory symptoms in PD. © 2016 Wiley Periodicals, Inc. PMID:26948282

  19. Clinical Features and Developing Risks of Saphenous Vein Thrombophlebitis

    PubMed Central

    2016-01-01

    We evaluated the clinical features and the risks of 14 patients with 14 limbs affected by saphenous vein thrombophlebitis from April 2007 to May 2013 and compared the results with patients undergoing operative repair of varicose veins (127 patients, 193 limbs) during the study period. The frequency of patients with a body mass index over 25 (78.6% vs. 35.3%, p = 0.0018), varicose change in the saphenous vein (78.6% vs. 6.2%, p <0.0001), and concurrent thrombosis in another vein (50.0% vs. 7.1%, p <0.0001) were all significantly higher than those of the patients under operative repair for varicose veins. These patients with clinical features above may be at an elevated risk of thrombophlebitis of the saphenous trunk. (This article is a translation of J Jpn Coll Angiol 2014; 54: 151–157). PMID:27375800

  20. Pineal cyst: a review of clinical and radiological features.

    PubMed

    Choy, Winward; Kim, Won; Spasic, Marko; Voth, Brittany; Yew, Andrew; Yang, Isaac

    2011-07-01

    Pineal cysts (PCs) are benign and often asymptomatic lesions of the pineal region that are typically small and do not change in size over time. PCs appear as small, well circumscribed, unilocular masses that either reside within or completely replace the pineal gland. This article reviews and discusses the characteristic features of PCs-clinical, histological, and identifiable by various imaging modalities-which assist clinicians in narrowing the differential diagnosis for pineal lesions. PMID:21801982

  1. The clinical features and management of pituitary apoplexy.

    PubMed Central

    Lloyd, M. H.; Belchetz, P. E.

    1977-01-01

    The clinical features and management of three patients presenting with pituitary apoplexy are described. They illustrate the difficulty of differentiating pituitary apoplexy from other acute neurologic conditions. One of the patients is the first reported case of pituitary apoplexy occurring in a histologically proved craniopharyngioma. Two of the cases reported were treated conservatively and recovered without seriouplexy as a neurosurgical emergency. The relationship between radiotherapy and pituitary apoplexy is discussed. PMID:876925

  2. [Clinical features of NMO according to brain MRI findings].

    PubMed

    Shimizu, Yuko

    2010-09-01

    Neuromyelitis optica (NMO) is a severe inflammatory, demyelinating disease, and its clinical characteristics include recurrent optic neuritis and longitudinally extensive transverse myelitis. The NMO-immunoglobulin (Ig) G auto-antibody (Ab), which binds to the aquaporin-4 (AQP4) water channel protein, is a marker for NMO. These clinical and immunological features have been used to distinguish NMO from multiple sclerosis (MS). In 1999, Wingerchuk et al. broadened the clinical criteria for diagnosing NMO to include "negative brain magnetic resonance imaging (MRI) at onset." However, after NMO-IgG/AQP4-Ab became a supportive criterion for diagnosing NMO, patients with NMO were frequently found to have symptomatic or asymptomatic brain lesions. In 2006, Pittock et al. reported that asymptomatic brain lesions were common in NMO, and that NMO brain lesions characteristically occurred in the hypothalamus and periventricular areas, which correspond to brain regions with high levels of AQP4 expression. Furthermore, Nakashima et al. detected abnormalities on brain MRI in 71% of NMO-IgG-positive Japanese patients. Patients with NMO have unique brain lesions that are clearly different from the lesions of patients with MS. In patients with NMO, involvement of the dorsal portion of the medulla oblongata causes intractable hiccups and nausea. Some studies described a hypothalamic lesion, and hypothalamic dysfunction could cause symptomatic hypersomnia, narcolepsy, and endocrinopathies. In some patients with NMO and NMO spectrum disorder who experience blood pressure fluctuations, vasogenic edema, manifesting as posterior reversible encephalopathy syndrome, may occur. In a recent report highlighting brain MRI with contrast enhancement, the most prominent feature that appeared to be a specific finding in NMO was "cloud-like enhancement" with multiple patchy enhancing lesions with a blurred margin. Another report showed that acute, large, edematous callosal lesions with

  3. Clinical and Echographic Features of Retinochoroidal and Optic Nerve Colobomas

    PubMed Central

    Venincasa, Vincent D.; Modi, Yasha S.; Aziz, Hassan A.; Ayres, Bernadette; Zehetner, Claus; Shi, Wei; Murray, Timothy G.; Flynn, Harry W.; Berrocal, Audina M.

    2015-01-01

    Purpose. We reported the clinical and echographic features of colobomas, prevalence of retinal detachment, and associated visual acuity in these patients Methods. The study is a nonrandomized consecutive case series of 140 colobomatous eyes in 98 patients (age range, 0–83 years). Coloboma depth, width, volume, and relative coloboma excavation (coloboma depth/axial length) were measured using standardized echographic images. The presence of structural and other ocular abnormalities was noted. The clinical and echographic findings present were correlated with visual acuity of the patient. In addition, these features were correlated with the presence or absence of retinal detachment. Results. Increased relative coloboma excavation was significantly associated with an increased risk of retinal detachment. A relative coloboma excavation (ratio of coloboma depth to axial length) greater than 0.15 was associated with an increased risk of retinal detachment (52%), compared to those with a relative coloboma excavation less than 0.15 (23%, P = 0.014). The presence of any structural abnormality and the presence of a retrobulbar cyst were associated with increased risk of retinal detachment and severe visual impairment (worse than 20/200). Increased coloboma depth, width, volume, and relative coloboma excavation were not associated with increased risk of severe visual impairment. Conclusions. Clinical and echographic features of colobomas may be used in predicting the risk of retinal detachment. Measuring relative coloboma excavation upon presentation may alter follow-up and assist in the diagnosis of retinal detachment. PMID:26047048

  4. Lung Cancer Gene Signatures and Clinical Perspectives

    PubMed Central

    Kuner, Ruprecht

    2013-01-01

    Microarrays have been used for more than two decades in preclinical research. The tumor transcriptional profiles were analyzed to select cancer-associated genes for in-deep functional characterization, to stratify tumor subgroups according to the histopathology or diverse clinical courses, and to assess biological and cellular functions behind these gene sets. In lung cancer—the main type of cancer causing mortality worldwide—biomarker research focuses on different objectives: the early diagnosis of curable tumor diseases, the stratification of patients with prognostic unfavorable operable tumors to assess the need for further therapy regimens, or the selection of patients for the most efficient therapies at early and late stages. In non-small cell lung cancer, gene and miRNA signatures are valuable to differentiate between the two main subtypes’ squamous and non-squamous tumors, a discrimination which has further implications for therapeutic schemes. Further subclassification within adenocarcinoma and squamous cell carcinoma has been done to correlate histopathological phenotype with disease outcome. Those tumor subgroups were assigned by diverse transcriptional patterns including potential biomarkers and therapy targets for future diagnostic and clinical applications. In lung cancer, none of these signatures have entered clinical routine for testing so far. In this review, the status quo of lung cancer gene signatures in preclinical and clinical research will be presented in the context of future clinical perspectives.

  5. Clinical features of early onset, familial Alzheimer`s disease linked to chromosome 14

    SciTech Connect

    Mullan, M.; Bennett, C.; Figueredo, C.; Crawford, F.

    1995-02-27

    Early onset familial Alzheimer`s disease (AD) has an autosomal dominant mode of inheritance. Two genes are responsible for the majority of cases of this subtype of AD. Mutations in the {beta}-amyloid precursor protein ({beta}APP) gene on chromosome 21 have been shown to completely cosegregate with the disease. We and others have previously described the clinical features of families with {beta}APP mutations at the codon 717 locus in an attempt to define the phenotype associated with a valine to isoleucine (Val {r_arrow} Ile) or a valine to glycine (Val {r_arrow} Gly) change. More recently, a second locus for very early onset disease has been localized to chromosome 14. The results of linkage studies in some families suggesting linkage to both chromosomes have been explained by the suggestion of a second (centromeric) locus on chromosome 21. Here we report the clinical features and genetic analysis of a British pedigree (F74) with early onset AD in which neither the {beta}APP locus nor any other chromosome 21 locus segregates with the disease, but in which good evidence is seen for linkage on the long arm of chromosome 14. In particular we report marker data suggesting that the chromosome 14 disease locus is close to D14S43 and D14S77. Given the likelihood that F74 represents a chromosome 14 linked family, we describe the clinical features and make a limited clinical comparison with the {beta}APP717 Val {r_arrow} Ile and {beta}APP717 Val {r_arrow} Gly encoded families that have been previously described. We conclude that although several previously reported clinical features occur to excess in early onset familial AD, no single clinical feature demarcates either the chromosome 14 or {beta}APP codon 717 mutated families except mean age of onset. 52 refs., 2 figs., 5 tabs.

  6. Genomic Features of Environmental and Clinical Vibrio parahaemolyticus Isolates Lacking Recognized Virulence Factors Are Dissimilar

    PubMed Central

    Petronella, N.; Chew Leung, C.; Pightling, A. W.; Banerjee, S. K.

    2015-01-01

    Vibrio parahaemolyticus is a bacterial pathogen that can cause illness after the consumption or handling of contaminated seafood. The primary virulence factors associated with V. parahaemolyticus illness are thermostable direct hemolysin (TDH) and Tdh-related hemolysin (TRH). However, clinical strains lacking tdh and trh have recently been isolated, and these clinical isolates are poorly understood. To help understand the emergence of clinical tdh- and trh-negative isolates, a genomic approach was used to comprehensively compare 4 clinical tdh- and trh-negative isolates with 16 environmental tdh- and trh-negative isolates and 34 clinical isolates positive for tdh or trh, or both, with the objective of identifying genomic features that are unique to clinical tdh- and trh-negative isolates. The prevalence of pathogenicity islands (PAIs) common to clinical isolates was thoroughly examined in each of the clinical tdh- and trh-negative isolates. The tdh PAI was not present in any clinical or environmental tdh- and trh-negative isolates. The trh PAI was not present in any environmental isolates; however, in clinical tdh- and trh-negative isolate 10-4238, the majority of the trh PAI including a partial trh1 gene was present, which resulted in reclassification of this isolate as a tdh-negative and trh-positive isolate. In the other clinical tdh- and trh-negative isolates, neither the trh gene nor the trh PAI was present. We identified 862 genes in clinical tdh- and trh-negative isolates but not in environmental tdh- and trh-negative isolates. Many of these genes are highly homologous to genes found in common enteric bacteria and included genes encoding a number of chemotaxis proteins and a novel putative type VI secretion system (T6SS) effector and immunity protein (T6SS1). The availability of genome sequences from clinical V. parahaemolyticus tdh- and trh-negative isolates and the comparative analysis may help provide an understanding of how this pathotype is able to

  7. Correlations Between Histopathologic Changes and Clinical Features in Pterygia

    PubMed Central

    Safi, Hamid; Kheirkhah, Ahmad; Mahbod, Mirgholamreza; Molaei, Saber; Hashemi, Hassan; Jabbarvand, Mahmoud

    2016-01-01

    Purpose: To investigate the correlations between clinical findings and histopathologic changes in eyes with pterygium. Methods: This prospective study included 70 eyes with primary pterygia undergoing surgical excision. Prior to surgery, clinical features of the pterygia including extension over the cornea, redness, fleshiness (based on obscuration of the underlying episcleral vessels), and obliteration of the plica semilunaris were determined. Postoperatively, pterygium specimens were examined by hematoxylin-eosin and trichrome staining to evaluate histopathologic characteristics including vascular density, leukocytic infiltration, stromal elastosis, stromal fibrosis and subepithelial fibrosis. Correlations between clinical findings and histopathologic changes were then investigated. Results: There was a marginally significant correlation between the redness and the fleshiness of pterygium (P = 0.06). Both redness and fleshiness of the pterygium had significant positive correlation with dimensions of the lesion over the cornea. Moreover, larger pterygia were associated with obliteration of the plica semilunaris. Pterygium redness showed a significant correlation with vascular density (P = 0.04), and pterygium fleshiness had a significant correlation with stromal fibrosis (P = 0.04). Pterygium dimensions over the cornea demonstrated a positive correlation with vascular density and a negative correlation with stromal elastosis. Conclusion: Redness and fleshiness of pterygium were only marginally correlated with each other, and each one showed a correlation with different histopathologic features. Larger pterygia were associated with more significant changes at the clinical and histopathologic levels.

  8. Clinical features of avian vacuolar myelinopathy in American coots

    USGS Publications Warehouse

    Larsen, R.S.; Nutter, F.B.; Augspurger, T.; Rocke, T.E.; Tomlinson, L.; Thomas, N.J.; Stoskopf, M.K.

    2002-01-01

    Objectivea??To characterize clinical features of avian vacuolar myelinopathy (AVM) in American coots. Designa??Case-control study. Animalsa??26 AVM-affected American coots and 12 unaffected coots. Proceduresa??Complete physical, neurologic, hematologic, and plasma biochemical evaluations were performed. Affected coots received supportive care. All coots died or were euthanatized, and AVM status was confirmed via histopathologic findings. Resultsa??3 severely affected coots were euthanatized immediately after examination. Seventeen affected coots were found dead within 7 days of admission, but 5 affected coots survived > 21 days and had signs of clinical recovery. Abnormal physical examination findings appeared to be related to general debilitation. Ataxia (88%), decreased withdrawal reflexes (88%), proprioceptive deficits (81%), decreased vent responses (69%), beak or tongue weakness (42%), and head tremors (31%), as well as absent pupillary light responses (46%), anisocoria (15%), apparent blindness (4%), nystagmus (4%), and strabismus (4%) were detected. Few gross abnormalities were detected at necropsy, but histologically, all AVM-affected coots had severe vacuolation of white matter of the brain. None of the control coots had vacuolation. Conclusions and Clinical Relevancea??Although there was considerable variability in form and severity of clinical neurologic abnormalities, clinical signs common in AVM-affected birds were identified. Clinical recovery of some AVM-affected coots can occur when supportive care is administered. Until the etiology is identified, caution should be exercised when rehabilitating and releasing coots thought to be affected by AVM.

  9. Clinicopathologic Features and Clinical Outcomes of Esophageal Gastrointestinal Stromal Tumor

    PubMed Central

    Feng, Fan; Tian, Yangzi; Liu, Zhen; Xu, Guanghui; Liu, Shushang; Guo, Man; Lian, Xiao; Fan, Daiming; Zhang, Hongwei

    2016-01-01

    Abstract Clinicopathologic features and clinical outcomes of gastrointestinal stromal tumors (GISTs) in esophagus are limited, because of the relatively rare incidence of esophageal GISTs. Therefore, the aim of the current study was to investigate the clinicopathologic features and clinical outcomes of esophageal GISTs, and to investigate the potential factors that may predict prognosis. Esophageal GIST cases were obtained from our center and from case reports and clinical studies extracted from MEDLINE. Clinicopathologic features and survivals were analyzed and compared with gastric GISTs from our center. The most common location was lower esophagus (86.84%), followed by middle and upper esophagus (11.40% and 1.76%). The majority of esophageal GISTs were classified as high-risk category (70.83%). Mitotic index was correlated with histologic type, mutational status, and tumor size. The 5-year disease-free survival and disease-specific survival were 65.1% and 65.9%, respectively. Tumor size, mitotic index, and National Institutes of Health risk classification were associated with prognosis of esophageal GISTs. Only tumor size, however, was the independent risk factor for the prognosis of esophageal GISTs. In comparison to gastric GISTs, the distribution of tumor size, histologic type, and National Institutes of Health risk classification were significantly different between esophageal GISTs and gastric GISTs. The disease-free survival and disease-specific survival of esophageal GISTs were significantly lower than that of gastric GISTs. The most common location for esophageal GISTs was lower esophagus, and most of the esophageal GISTs are high-risk category. Tumor size was the independent risk factor for the prognosis of esophageal GISTs. Esophageal GISTs differ significantly from gastric GISTs in respect to clinicopathologic features. The prognosis of esophageal GISTs was worse than that of gastric GISTs. PMID:26765432

  10. Familial predisposition to adrenocortical tumors: clinical and biological features and management strategies.

    PubMed

    Ribeiro, Raul C; Pinto, Emilia M; Zambetti, Gerard P

    2010-06-01

    The incidence of adrenocortical tumors (ACTs) is increased in several familial cancer syndromes resulting from abnormalities in genes that encode transcription factors implicated in cell proliferation, differentiation, senescence, apoptosis, and genomic instability. These include P53, MEN1, APC, and PRKAR1A. Adenomas are the most common ACTs, but adrenocortical carcinomas occur rarely as well. The clinical manifestations of ACTs, which result from increased secretion of adrenocortical hormones, are similar in the familial and sporadic forms of the disease. However, their management may differ because of unique aspects of the constitutional syndromes. The analysis of gene expression profiles of ACTs in these constitutional syndromes have contributed to our understanding of adrenal tumorigenesis and revealed new molecular diagnostic and prognostic markers and candidate genes for targeted therapies. This chapter summarizes the clinical and biological features, pathogenesis, and management strategies for ACTs that develop in patients with familial cancer syndrome. PMID:20833338

  11. AB124. Mucolipidosis type II: clinical features and laboratories

    PubMed Central

    Can, Ngoc Thi Bich; Vu, Dung Chi; Bui, Thao Phuong; Nguyen, Khanh Ngoc; Hwu, Wuh-Liang

    2015-01-01

    Background I-cell disease (Mucolipidosis II) is a rare lysosomal storage disorder caused by the deficiency of N-acetylglucosamine-l-phosphotransferase, an enzyme that transfers phosphate groups onto oligosaccharide units of lysosomal enzyme precursors. Due to the absence of transferase activity, the common phosphomannose recognition marker of acid hydrolases is not generated, and the enzymes are not targeted to the lysosomes I. As a consequence the enzymes are secreted into the extracellular space, and high activities can be found in the serum, cerebrospinal fluid and urine of the patients, whereas inside the cells (fibroblasts) the enzyme levels are considerably reduced. Mucolipidosis is also known as I-cell disease because of the coarse granular cytoplasmic inclusions seen in cultured skin fibroblasts which are large lysosomes containing heterogeneous material. Objective To describe clinical features and enzyme activity of patients with mucolipidosis type II. Methods Clinical features, laboratory and plasma lysosom enzyme activity by four MU-Fluorometric assay was study. Results and conclusions Sixteen cases (seven girls and nine boys) onset at 5.93±4.28 years of age the onset age of 2.3±3.1 years (median 1.25) with the feature of joint stiffness and bone deformation. 100% cases admitted with the feature of joint stiffness, chest deformation and kyphoscoliosis, 93.3% coarse facial features. No patients had hepatosplenomegaly on ultrasound, 5/15 patients had heart valves disease. Enzyme assay showed α-Hexosaminidase of 1,885.98±338.7 nmoL/mg plasma/17 h, α-Iduronate sulfatase of 4,534.78±1,062.97 nmoL/mg plasma/4 h. Mucolipidosis has seriously affected the life of the patients.

  12. Clinical features for diagnosis and management of patients with PRDM12 congenital insensitivity to pain

    PubMed Central

    Zhang, Stella; Malik Sharif, Saghira; Chen, Ya-Chun; Valente, Enza-Maria; Ahmed, Mushtaq; Sheridan, Eamonn; Bennett, Christopher; Woods, Geoffrey

    2016-01-01

    Background Congenital insensitivity to pain (CIP) is a rare extreme phenotype characterised by an inability to perceive pain present from birth due to lack of, or malfunction of, nociceptors. PRDM12 has recently been identified as a new gene that can cause CIP. The full phenotype and natural history have not yet been reported. Methods We have ascertained five adult patients and report their clinical features. Results Based on our findings, and those of previous patients, we describe the natural history of the PRDM12-CIP disorder, and derive diagnostic and management features to guide the clinical management of patients. Conclusions PRDM12-CIP is a distinct and diagnosable disorder, and requires specific clinical management to minimise predictable complications. PMID:26975306

  13. Idiopathic Pulmonary Fibrosis: Epidemiology, Clinical Features, Prognosis, and Management.

    PubMed

    Lynch, Joseph P; Huynh, Richard H; Fishbein, Michael C; Saggar, Rajan; Belperio, John A; Weigt, S Sam

    2016-06-01

    Idiopathic pulmonary fibrosis (IPF) is a specific form of chronic interstitial lung pneumonia associated with the histologic pattern of usual interstitial pneumonia (UIP). Although UIP is a distinct histologic lesion, this histologic pattern is not specific for IPF and can also be found in other diseases (e.g., connective tissue disease and asbestosis). Clinical features of IPF include progressive cough, dyspnea, restrictive ventilatory defect, and progressive fibrosis and destruction of the lung parenchyma. IPF is rare (13-42 cases/100,000), and primarily affects older adults (>50 years of age). The diagnosis of IPF often requires surgical lung biopsy, but the diagnosis can be affirmed with confidence in some patients provided the results of computed tomographic (CT) scans and clinical features are consistent. The clinical course is variable, but inexorable progression (typically over months to years) is typical. Mean survival from the onset of symptoms approximates 3 to 5 years. Medical treatment is only modestly effective, primarily by slowing the rate of disease progression. Lung transplantation is the best therapeutic option. PMID:27231859

  14. Modeling gene expression using chromatin features in various cellular contexts

    PubMed Central

    2012-01-01

    Background Previous work has demonstrated that chromatin feature levels correlate with gene expression. The ENCODE project enables us to further explore this relationship using an unprecedented volume of data. Expression levels from more than 100,000 promoters were measured using a variety of high-throughput techniques applied to RNA extracted by different protocols from different cellular compartments of several human cell lines. ENCODE also generated the genome-wide mapping of eleven histone marks, one histone variant, and DNase I hypersensitivity sites in seven cell lines. Results We built a novel quantitative model to study the relationship between chromatin features and expression levels. Our study not only confirms that the general relationships found in previous studies hold across various cell lines, but also makes new suggestions about the relationship between chromatin features and gene expression levels. We found that expression status and expression levels can be predicted by different groups of chromatin features, both with high accuracy. We also found that expression levels measured by CAGE are better predicted than by RNA-PET or RNA-Seq, and different categories of chromatin features are the most predictive of expression for different RNA measurement methods. Additionally, PolyA+ RNA is overall more predictable than PolyA- RNA among different cell compartments, and PolyA+ cytosolic RNA measured with RNA-Seq is more predictable than PolyA+ nuclear RNA, while the opposite is true for PolyA- RNA. Conclusions Our study provides new insights into transcriptional regulation by analyzing chromatin features in different cellular contexts. PMID:22950368

  15. The clinical profile and pathophysiology of atrial fibrillation: relationships among clinical features, epidemiology, and mechanisms.

    PubMed

    Andrade, Jason; Khairy, Paul; Dobrev, Dobromir; Nattel, Stanley

    2014-04-25

    Atrial fibrillation (AF) is the most common arrhythmia (estimated lifetime risk, 22%-26%). The aim of this article is to review the clinical epidemiological features of AF and to relate them to underlying mechanisms. Long-established risk factors for AF include aging, male sex, hypertension, valve disease, left ventricular dysfunction, obesity, and alcohol consumption. Emerging risk factors include prehypertension, increased pulse pressure, obstructive sleep apnea, high-level physical training, diastolic dysfunction, predisposing gene variants, hypertrophic cardiomyopathy, and congenital heart disease. Potential risk factors are coronary artery disease, kidney disease, systemic inflammation, pericardial fat, and tobacco use. AF has substantial population health consequences, including impaired quality of life, increased hospitalization rates, stroke occurrence, and increased medical costs. The pathophysiology of AF centers around 4 general types of disturbances that promote ectopic firing and reentrant mechanisms, and include the following: (1) ion channel dysfunction, (2) Ca(2+)-handling abnormalities, (3) structural remodeling, and (4) autonomic neural dysregulation. Aging, hypertension, valve disease, heart failure, myocardial infarction, obesity, smoking, diabetes mellitus, thyroid dysfunction, and endurance exercise training all cause structural remodeling. Heart failure and prior atrial infarction also cause Ca(2+)-handling abnormalities that lead to focal ectopic firing via delayed afterdepolarizations/triggered activity. Neural dysregulation is central to atrial arrhythmogenesis associated with endurance exercise training and occlusive coronary artery disease. Monogenic causes of AF typically promote the arrhythmia via ion channel dysfunction, but the mechanisms of the more common polygenic risk factors are still poorly understood and under intense investigation. Better recognition of the clinical epidemiology of AF, as well as an improved appreciation of

  16. Clinical Applications Involving CNS Gene Transfer

    PubMed Central

    Kantor, Boris; McCown, Thomas; Leone, Paola; Gray, Steven J.

    2015-01-01

    Diseases of the central nervous system (CNS) have traditionally been the most difficult to treat by traditional pharmacological methods, due mostly to the blood–brain barrier and the difficulties associated with repeated drug administration targeting the CNS. Viral vector gene transfer represents a way to permanently provide a therapeutic protein within the nervous system after a single administration, whether this be a gene replacement strategy for an inherited disorder or a disease-modifying protein for a disease such as Parkinson's. Gene therapy approaches for CNS disorders has evolved considerably over the last two decades. Although a breakthrough treatment has remained elusive, current strategies are now considerably safer and potentially much more effective. This chapter will explore the past, current, and future status of CNS gene therapy, focusing on clinical trials utilizing adeno-associated virus and lentiviral vectors. PMID:25311921

  17. Cardiovascular Magnetic Resonance Myocardial Feature Tracking: Concepts and Clinical Applications.

    PubMed

    Schuster, Andreas; Hor, Kan N; Kowallick, Johannes T; Beerbaum, Philipp; Kutty, Shelby

    2016-04-01

    Heart failure-induced cardiovascular morbidity and mortality constitute a major health problem worldwide and result from diverse pathogeneses, including coronary artery disease, nonischemic cardiomyopathies, and arrhythmias. Assessment of cardiovascular performance is important for early diagnosis and accurate management of patients at risk of heart failure. During the past decade, cardiovascular magnetic resonance myocardial feature tracking has emerged as a useful tool for the quantitative evaluation of cardiovascular function. The method allows quantification of biatrial and biventricular mechanics from measures of deformation: strain, torsion, and dyssynchrony. The purpose of this article is to review the basic principles, clinical applications, accuracy, and reproducibility of cardiovascular magnetic resonance myocardial feature tracking, highlighting the prognostic implications. It will also provide an outlook on how this field might evolve in the future. PMID:27009468

  18. Clinical features of allergic rhinitis in children of Shanghai, China.

    PubMed

    He, S; Li, Y J; Chen, J

    2016-01-01

    The aims of the current study were to assess the clinical features of allergic rhinitis (AR) in children in Shanghai. Serum-specific IgE (sIgE) tests were performed on samples from patients with AR symptoms from January 2011 to December 2014. A disease-related questionnaire was completed after AR diagnosis. The allergen profile and clinical features of AR were analyzed. In total, 2713 AR patients were enrolled in this study. Dermatophagoides pteronyssinus was found to be the most common offending allergen in the study population. With increasing age, the prevalence of sIgE against inhalant allergens was significantly increased; however, the opposite trend was observed for food allergens. Additionally, the proportion of children with high levels of sIgE against D. pteronyssinus increased with age. Of the AR cases, 8.6% were classified as intermittent mild, 4.2% as persistent mild, 40.5% as intermittent moderate-severe, and 46.7% as persistent moderate-severe. A family history of allergies and a patient history of allergies within 6 months of birth were significantly associated with the duration and severity of AR symptoms. The occurrence of co-morbidities, such as allergic conjunctivitis, cough, and asthma, gradually increased from intermittent mild, persistent mild, and intermittent moderate-severe to persistent moderate-severe. The most frequently used drugs were topical corticosteroids and oral antihistamines, which were used by 86.7 and 79.0% of patients, respectively. These results confirm the adequacy of the Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines for classifying AR patients, and advance the understanding of clinical features of AR in children in Shanghai, China. PMID:27173334

  19. Clinical and microbiologic features of dacryocystitis-related orbital cellulitis.

    PubMed

    Wladis, Edward J; Shinder, Roman; LeFebvre, Daniel R; Sokol, Jason A; Boyce, Michelle

    2016-10-01

    Dacryocystitis-related orbital cellulitis is a relatively rare condition, and large case series of this clinical entity have been reported. This study was undertaken to identify a larger cohort of patients with this ailment, with the intent of defining its clinical and microbiologic features. Case logs from four institutions were reviewed to identify patients that suffered from dacryocystitis-related orbital cellulitis. A retrospective chart review was then performed to identify clinical features, management strategies, microbiologic features, and outcomes. A dedicated statistical software package was utilized to identify correlations between these variables. 13 patients (7 females, 6 males; mean age = 57.2 years, range = 7-89 years) were identified. One patient carried a diagnosis of immunosuppressive disease. All patients underwent emergent surgical drainage and received intravenous antibiotics. Primary acquired nasolacrimal duct obstruction was found to be the underlying etiology in nine cases (69.2%), whereas four patients suffered from specific causes of their obstructions. An average of 1.07 organisms/patient (standard deviation = 0.49 organisms/patient) were recovered from microbiologic cultures, and Gram-positive bacteria represented the majority of cultured organisms. All patients experienced either stable or improved vision upon discharge. The relationships between a specific etiology and the possibility of vision loss or the number of organisms cultured, between the number of organisms cultured and vision loss, and immunosuppression and vision loss or the number of organisms cultured were all not statistically significant (p > 0.05). Dacryocystitis-related orbital cellulitis most commonly occurs in adult patients who do not carry immunosuppressive diagnoses and suffer from primary obstructions. Multiple microbiologic species may cause this problem, although Gram-positive organisms are most common. With appropriate management, stable or improved vision

  20. Clinical Features of Genetic Cardiac Diseases Related to Potassium Channelopathies.

    PubMed

    Adler, Arnon; Viskin, Sami

    2016-06-01

    Genetic cardiac diseases related to potassium channelopathies are a group of relatively rare syndromes that includes long QT syndrome, short QT syndrome, Brugada syndrome, and early repolarization syndrome. Patients with these syndromes share a propensity for the development of life-threatening ventricular arrhythmias in the absence of significant cardiac structural abnormalities. Familial atrial fibrillation has also been associated with potassium channel dysfunction but differs from the other syndromes by being a rare cause of a common condition. This article focuses on the clinical features, diagnosis, and management of these syndromes. PMID:27261827

  1. Streptococcal necrotising fasciitis: comparison between histological and clinical features.

    PubMed Central

    Barker, F G; Leppard, B J; Seal, D V

    1987-01-01

    Nineteen acute and 17 subacute cases of necrotising fasciitis due to beta haemolytic streptococci are described. Excised tissue from seven and four cases, respectively, was available for histological examination. The two clinical types showed remarkable similarities, with inflammation and necrosis from epidermis to subcutaneous fat. Haemorrhage was present in variable amounts in both types. Gram positive cocci were not always identified in tissue, nor cultured, when serological tests were required to confirm the diagnosis. The only apparent difference between the acute and subacute type was the higher incidence of thrombi in some blood vessels of acute cases, whereas patent vessels or recanalized thrombus were usually found in subacute cases. This quantitative difference in the degree of thrombosis may alone be responsible for the varying clinical features and response to antibiotics. Images Fig 2 Fig 3 Fig 4a Fig 4b Fig 1 PMID:3558868

  2. [The epidemiological and clinical features of 208 patients with trichinosis].

    PubMed

    Wang, Z; Cui, J; Jin, X

    1996-06-01

    In order to know the epidemiological and clinical features of trichinosis, the data of 208 patients with trichinosis from 1992 to 1994 were analysed. The results showed that these patients came from 11 districts, and acquired the infection mainly by tasting the raw pork filling for dumplings or ingesting instant-boiled pork or mutton. The incidence of trichinosis is high in winter. Young and middle-aged workers and cadres constituted the majority of the patients and the infection was more common in the males than in females. The main clinical manifestations of trichinosis were prolonged fever, general myalgia, muscle weekness and eosinophilia. Most of the patients had no gastrointestinal symptoms and skin eruption. Eyelid edema was only seen in the early stage. Serological tests were significant value in the diagnosis of trichinosis. The key measures to prevent trichinosis were that meat inspection should be strictly carried out and bad eating habit changed. PMID:9387626

  3. Clinical and Pathologic Features of Secondary Acute Promyelocytic Leukemia

    PubMed Central

    Duffield, Amy S.; Aoki, Joseph; Levis, Mark; Cowan, Kathleen; Gocke, Christopher D.; Burns, Kathleen H.; Borowitz, Michael J.; Vuica-Ross, Milena

    2013-01-01

    Acute promyelocytic leukemia (APL) is a relatively common form of acute myeloid leukemia (AML) that has an excellent prognosis. In contrast, secondary acute myeloid leukemias, including therapy-related AML and AML with myelodysplasia-related changes, have a relatively poor prognosis. We identified 9 cases of APL at our institution in which there was a history of chemotherapy, radiotherapy, chronic immunosuppression, or antecedent myelodysplastic syndrome. The clinical and pathologic findings in these cases of secondary APL were compared with the clinical and pathologic findings in cases of de novo APL. We found that secondary and de novo APL had abnormal promyelocytes with similar morphologic and immunophenotypic features, comparable cytogenetic findings, comparable rates of FMS-like tyrosine kinase mutations, and similar rates of recurrent disease and death. These data suggest that secondary APL is similar to de novo APL and, thus, should be considered distinct from other secondary acute myeloid neoplasms. PMID:22338051

  4. Hypertrophic cardiomyopathy in infants: clinical features and natural history

    SciTech Connect

    Maron, B.J.; Tajik, A.J.; Ruttenberg, H.D.; Graham, T.P.; Atwood, G.F.; Victorica, B.E.; Lie, J.T.; Roberts, W.C.

    1982-01-01

    The clinical and morphologic features of hypertrophic cardiomyopathy in 20 patients recognized as having cardiac disease in the first year of life are described. Fourteen of these 20 infants were initially suspected of having heart disease solely because a heart murmur was identified. However, the infants showed a variety of clinical findings, including signs of marked congestive heart failure (in the presence of nondilated ventricular cavities and normal or increased left ventricular contractility) and substantial cardiac enlargement on chest radiograph. Other findings were markedly different from those usually present in older children and adults with hypertrophic cardiomyopathy (e.g., right ventricular hypertrophy on the ECG and cyanosis). Consequently, in 14 infants, the initial clinical diagnosis was congenital cardiac malformation other than hypertrophic cardiomyopathy. The clinical course was variable in these patients, but the onset of marked congestive heart failure in the first year of life appeared to be an unfavorable prognostic sign; nine of the 11 infants with congestive heart failure died within the first year of life. In infants with hypertrophic cardiomyopathy, unlike older children and adults with this condition, sudden death was less common (two patients) than death due to progressive congestive heart failure.

  5. Histomorphological Features of Intestinal Atresia and its Clinical Correlation

    PubMed Central

    Singh, Meeta; Khurana, Nita; Sathish, Agarwal

    2015-01-01

    Introduction Intestinal atresia accounts for approximately one third of all cases of neonatal intestinal obstruction. There is controversy regarding pathogenesis of congenital atresia and stenosis of small bowel. Studies regarding clinical manifestations and specific histopathological features of neonatal intestinal atresia are scarce in Indian literature. Aim To understand the histomorphological features and thus suggest pathophysiology of cases with Intestinal Atresia. Materials and Methods Out of 147 cases, of intestinal obstruction in newborn studied over a period of 5 years, 39 cases of intestinal atresia were found. Their histomorphological details with clinical manifestations were studied. Results Type II was the commonest type of atresia. Associated anomalies noted were gastroschisis, volvulus, anal stenosis, microcolon, annular pancreas, meconium cyst and duplication cyst. Histological changes observed were ulceration, flattening, abnormal villous configuration, luminal obliteration, narrowing, haemangiomatous proliferation of blood vessels, fibrosis, haemorrhage, calcification, and mesenchymal condensation around the blood vessels. Gangrene and perforation has also noted in some cases. Conclusion An intrauterine intestinal ischemia due to vascular pathology followed by resorption of the bowel is the possible explanation for the development of intestinal atresia. PMID:26674207

  6. Mutations in epilepsy and intellectual disability genes in patients with features of Rett syndrome.

    PubMed

    Olson, Heather E; Tambunan, Dimira; LaCoursiere, Christopher; Goldenberg, Marti; Pinsky, Rebecca; Martin, Emilie; Ho, Eugenia; Khwaja, Omar; Kaufmann, Walter E; Poduri, Annapurna

    2015-09-01

    Rett syndrome and neurodevelopmental disorders with features overlapping this syndrome frequently remain unexplained in patients without clinically identified MECP2 mutations. We recruited a cohort of 11 patients with features of Rett syndrome and negative initial clinical testing for mutations in MECP2. We analyzed their phenotypes to determine whether patients met formal criteria for Rett syndrome, reviewed repeat clinical genetic testing, and performed exome sequencing of the probands. Using 2010 diagnostic criteria, three patients had classical Rett syndrome, including two for whom repeat MECP2 gene testing had identified mutations. In a patient with neonatal onset epilepsy with atypical Rett syndrome, we identified a frameshift deletion in STXBP1. Among seven patients with features of Rett syndrome not fulfilling formal diagnostic criteria, four had suspected pathogenic mutations, one each in MECP2, FOXG1, SCN8A, and IQSEC2. MECP2 mutations are highly correlated with classical Rett syndrome. Genes associated with atypical Rett syndrome, epilepsy, or intellectual disability should be considered in patients with features overlapping with Rett syndrome and negative MECP2 testing. While most of the identified mutations were apparently de novo, the SCN8A variant was inherited from an unaffected parent mosaic for the mutation, which is important to note for counseling regarding recurrence risks. PMID:25914188

  7. Duplication 2p25 in a child with clinical features of CHARGE syndrome.

    PubMed

    Sperry, Ethan D; Schuette, Jane L; van Ravenswaaij-Arts, Conny M A; Green, Glenn E; Martin, Donna M

    2016-05-01

    CHARGE syndrome is a dominant disorder characterized by ocular colobomata, heart defects, choanal atresia, retardation of growth and development, genital hypoplasia, and ear abnormalities including deafness and vestibular disorders. The majority of individuals with CHARGE have pathogenic variants in the gene encoding CHD7, a chromatin remodeling protein. Here, we present a 15-year-old girl with clinical features of CHARGE syndrome and a de novo 6.5 Mb gain of genomic material at 2p25.3-p25.2. The duplicated region contained 24 genes, including the early and broadly expressed transcription factor gene SOX11. Analysis of 28 other patients with CHARGE showed no SOX11 copy number changes or pathogenic sequence variants. To our knowledge, this child's chromosomal abnormality is unique and represents the first co-occurrence of duplication 2p25 and clinical features of CHARGE syndrome. We compare our patient's phenotype to ten previously published patients with isolated terminal duplication 2p, and elaborate on the clinical diagnosis of CHARGE in the context of atypical genetic findings. © 2016 Wiley Periodicals, Inc. PMID:26850571

  8. Clinical Features and Management of a Median Cleft Lip

    PubMed Central

    Kim, Do Yeon; Oh, Tae Suk

    2016-01-01

    Background Median cleft lip is a rare anomaly consisting of a midline vertical cleft through the upper lip. It can also involve the premaxillary bone, the nasal septum, and the central nervous system. In our current report, we present the clinical features of 6 patients with a median cleft lip and their surgical management according to the accompanying anomalies. Methods From December 2010 to January 2014, 6 patients with a median cleft lip were reviewed. Five of these cases underwent surgical correction; alveolar bone grafting was performed in a patient with a median alveolar cleft. The surgical technique included inverted-U excision of the upper lip and repair of the orbicularis oris muscle. The mean follow-up period was 20.4 months (range, 7.4–44.0 months). Results The study patients presented various anomalous features. Five patients received surgical correction, 4 with repair of the median cleft lip, and one with iliac bone grafting for median alveolar cleft. A patient with basal sphenoethmoidal meningocele was managed with transoral endoscopic surgery for repair of the meningocele. Successful surgical repair was achieved in all cases with no postoperative complications. Conclusions Relatively mild forms of median cleft lip can be corrected with inverted-U excision with good aesthetic outcomes. In addition, there is a broad spectrum of clinical features and various anomalies, such as nasal deformity, alveolar cleft, and short upper frenulum, which require close evaluation. The timing of the operation should be decided considering the presence of other anomalies that can threaten patient survival. PMID:27218021

  9. Clinical Features of Liver Cancer with Cerebral Hemorrhage

    PubMed Central

    Lu, Qiuhong; Chen, Li; Zeng, Jinsheng; Huang, Gelun; Qin, Chao; Cheng, Daobin; Yu, Lixia; Liang, Zhijian

    2016-01-01

    Background Cerebral hemorrhage is common in patients with cancer, but the clinical features and pathogenesis of liver cancer patients with cerebral hemorrhage are not well known. Material/Methods Liver cancer patients who developed cerebral hemorrhage were recruited from the First Affiliated Hospital of Guangxi Medical University between January 2003 and December 2014. We retrospectively analyzed clinical presentations, results of laboratory tests, and imaging examinations. The clinical features and pathogenesis were summarized. Results Among 11133 patients with liver cancer, 9 patients (0.08%), including 3 females and 6 males met the inclusion criteria. The age range was 48–73 years and the average age was 61.67±8.97 years. Five patients did not have traditional hemorrhage risk factors and 4s had the risk factors; however, all had developed hepatocellular carcinoma, and 3 had developed metastasis. All 9 patients showed elevated tumor markers: an increased AFP level was detected in 6 patients, coagulation dysfunctions in 8 patients, and abnormal liver functions in 6 patients. Five patients had developed cerebral hemorrhagic lesions in the lobes of their brains, while hemorrhagic lesions in the basal ganglia occurred in 3 patients and in the brainstem in only 1 patient. Four patients had clear consciousness, while 5 patients were in coma and showed poor prognosis. Conclusions Patients who have liver cancer complicated with cerebral hemorrhage usually lack traditional risk factors of cerebral hemorrhage. The site of cerebral hemorrhage is often detected in the lobes of the brain. Coagulation dysfunctions might be the main pathogenesis of liver cancer complicated with cerebral hemorrhage. PMID:27209058

  10. Clinical Features of Liver Cancer with Cerebral Hemorrhage.

    PubMed

    Lu, Qiuhong; Chen, Li; Zeng, Jinsheng; Huang, Gelun; Qin, Chao; Cheng, Daobin; Yu, Lixia; Liang, Zhijian

    2016-01-01

    BACKGROUND Cerebral hemorrhage is common in patients with cancer, but the clinical features and pathogenesis of liver cancer patients with cerebral hemorrhage are not well known. MATERIAL AND METHODS Liver cancer patients who developed cerebral hemorrhage were recruited from the First Affiliated Hospital of Guangxi Medical University between January 2003 and December 2014. We retrospectively analyzed clinical presentations, results of laboratory tests, and imaging examinations. The clinical features and pathogenesis were summarized. RESULTS Among 11133 patients with liver cancer, 9 patients (0.08%), including 3 females and 6 males met the inclusion criteria. The age range was 48-73 years and the average age was 61.67±8.97 years. Five patients did not have traditional hemorrhage risk factors and 4s had the risk factors; however, all had developed hepatocellular carcinoma, and 3 had developed metastasis. All 9 patients showed elevated tumor markers: an increased AFP level was detected in 6 patients, coagulation dysfunctions in 8 patients, and abnormal liver functions in 6 patients. Five patients had developed cerebral hemorrhagic lesions in the lobes of their brains, while hemorrhagic lesions in the basal ganglia occurred in 3 patients and in the brainstem in only 1 patient. Four patients had clear consciousness, while 5 patients were in coma and showed poor prognosis. CONCLUSIONS Patients who have liver cancer complicated with cerebral hemorrhage usually lack traditional risk factors of cerebral hemorrhage. The site of cerebral hemorrhage is often detected in the lobes of the brain. Coagulation dysfunctions might be the main pathogenesis of liver cancer complicated with cerebral hemorrhage. PMID:27209058

  11. Clinical and diagnostic features of patients with suspected Klinefelter syndrome.

    PubMed

    Kamischke, Axel; Baumgardt, Arthur; Horst, Jürgen; Nieschlag, Eberhard

    2003-01-01

    Klinefelter syndrome, with an incidence of 1:600 male newborns, is the most frequent form of male hypogonadism. However, despite its relatively high frequency, the syndrome is often overlooked. To prevent such oversights, the clinical features should be better characterized, and simple screening tests should be used more frequently. In a cohort of 309 patients suspected of having Klinefelter syndrome, we evaluated the clinical symptoms as well as the diagnostic value of the Barr body test for screening procedures. On the basis of chromosome analysis, 85 patients (group I) were diagnosed as having Klinefelter syndrome, and 224 patients had a 46,XY karyotype (group II). Barr body analysis revealed a specificity of 95% and a sensitivity of 82% for the diagnosis of Klinefelter syndrome. General features (eg, reason for admission, age, age of the parents, body weight, and frequency of maldescended testes) were not different between the groups, except that group I had a higher proportion of patients with a lower educational background. Compared to group II, patients with Klinefelter syndrome were taller (P <.001); had smaller testis volumes (P <.0001), higher follicle-stimulating hormone (FSH) and luteinizing hormone (LH) values; and carried a tendency for less androgenic phenotype and secondary hair distribution. Testosterone, estradiol, sex hormone-binding globulin (SHBG), and prostate-specific antigen (PSA) serum levels as well as prostate volume were not significantly different between the groups. In patients who provided an ejaculate, azoospermia was found in 54% of the patients in group II and in 93% of the patients with Klinefelter syndrome. Although not exclusively characteristic for Klinefelter syndrome, the combination of low testicular volume and azoospermia, together with elevated gonadotropins, is highly indicative for a Klinefelter syndrome and should stimulate further clinical investigations. Barr body analysis provides a quick and reliable screening test

  12. Cardioembolic Stroke: Clinical Features, Specific Cardiac Disorders and Prognosis

    PubMed Central

    Arboix, Adrià; Alió, Josefina

    2010-01-01

    This article provides the reader with an overview and up-date of clinical features, specific cardiac disorders and prognosis of cardioembolic stroke. Cardioembolic stroke accounts for 14-30% of ischemic strokes and, in general, is a severe condition; patients with cardioembolic infarction are prone to early and long-term stroke recurrence, although recurrences may be preventable by appropriate treatment during the acute phase and strict control at follow-up. Certain clinical features are suggestive of cardioembolic infarction, including sudden onset to maximal deficit, decreased level of consciousness at onset, Wernicke’s aphasia or global aphasia without hemiparesis, a Valsalva manoeuvre at the time of stroke onset, and co-occurrence of cerebral and systemic emboli. Lacunar clinical presentations, a lacunar infarct and especially multiple lacunar infarcts, make cardioembolic origin unlikely. The more common high risk cardioembolic conditions are atrial fibrillation, recent myocardial infarction, mechanical prosthetic valve, dilated myocardiopathy, and mitral rheumatic stenosis. Transthoracic and transesophageal echocardiogram can disclose structural heart diseases. Paroxysmal atrial dysrhyhtmia can be detected by Holter monitoring. In-hospital mortality in cardioembolic stroke (27.3%, in our series) is the highest as compared with other subtypes of cerebral infarction. In our experience, in-hospital mortality in patients with early embolic recurrence (within the first 7 days) was 77%. Patients with alcohol abuse, hypertension, valvular heart disease, nausea and vomiting, and previous cerebral infarction are at increased risk of early recurrent systemic embolization. Secondary prevention with anticoagulants should be started immediately if possible in patients at high risk for recurrent cardioembolic stroke in which contraindications, such as falls, poor compliance, uncontrolled epilepsy or gastrointestinal bleeding are absent. PMID:21804774

  13. An Overview of Rare and Unusual Clinical Features of Bietti’s Crystalline Dystrophy

    PubMed Central

    Osman Saatci, Ali; Can Doruk, Hasan

    2014-01-01

    Bietti’s crystalline dystrophy (BCD) is a rare disease presenting with the appearance of intraretinal crystalline deposits and varying degrees of chorioretinal atrophy commencing at the posterior pole. Within time, intraretinal crystals gradually disappear and chorioretinal atrophy extends beyond the macula even resulting in complete chorioretinal atrophy. Concomitant corneal crystals can be noted in 1/2 - 1/3 of the patients, and the presence of corneal crystals is not a must for establishing the diagnosis. For the past decade, genetic evaluations and newer imaging modalities expand our knowledge about the disease. CYP4V2 gene is found to be the gene responsible for the disease process and new mutations are still being described. Modern imaging modalities, such as a spectral domain optical coherence tomography (SD-OCT) shed light on the anatomic features of the disease. By this, we reiterate the rare and unusual clinical features of BCD. PMID:25738160

  14. Abdominal Wall Endometrioma: Ultrasonographic Features and Correlation with Clinical Findings

    PubMed Central

    Solak, Aynur; Genç, Berhan; Yalaz, Seyhan; Şahin, Neslin; Sezer, Taylan Özgür; Solak, İlhami

    2013-01-01

    Background: The diagnosis of abdominal wall endometrioma (AWE) is often confused with other surgical conditions. Certain factors relating to knowledge of the clinical history of the disease make correct diagnosis and treatment difficult. Aims: To present the clinical findings and ultrasonographic (US) features of AWE with special emphasis on size-related features. Study Design: This study reviewed abdominal wall endometriomas during a 2-year period in the Radiology Department of Sifa University Hospital, Izmir. Methods: Eleven women (mean age 32.6 years) with 12 scar endometriomas (mean diameter 29.2 mm) were consecutively evaluated by US and Colour Doppler examination (CDUS) prior to surgery. Lesions were grouped into large (≥3 cm) and small nodules. Vascularisation was classified as location (central, peripheral and mixed) and severity (absent, moderately vascular and hypervascular). In each patient, the nature of pain (absent, cyclic: associated with menstruation and continuous), historical and clinical data were documented. Four patients underwent Magnetic Resonance Imaging and their findings were presented. Fisher’s exact test, χ2 test for categorical data and the unpaired T-test for continuous variables were used for statistical analysis. Results: In all the women, US of the AWE showed the presence of a solid hypoechoic mass (less echogenic than the surrounding hyperechoic fat) within the abdominal wall. There was a significant correlation between AWE sizes with repeated caesareans and the mean time between the last operation and admission to hospital (p<0.05). Large endometriomas showed increased central vascularity (p<0.05). Cyclic pain was more frequent in small lesions, whereas continuous pain was more commonly found in patients with larger lesions (p<0.05). Conclusion: AWE is often misdiagnosed clinically because endometriosis may occur years after the caesarean section, the pain is often non-cyclic in nature, and there is not always a palpable

  15. Clinical Features of Severe or Fatal Mycoplasma pneumoniae Pneumonia

    PubMed Central

    Izumikawa, Koichi

    2016-01-01

    Mycoplasma pneumoniae is one of the most common causes of community-acquired pneumonia in children and young adults. The incidence of fulminant M. pneumoniae pneumonia (MPP) is relatively rare despite the high prevalence of M. pneumoniae infection. This literature review highlights the clinical features of fulminant MPP by examining the most recent data in epidemiology, clinical presentation, pathogenesis, and treatment. Fulminant MPP accounts for 0.5–2% of all MPP cases and primarily affects young adults with no underlying disease. Key clinical findings include a cough, fever, and dyspnea along with diffuse abnormal findings in radiological examinations. Levels of inflammatory markers such as white blood cells and C-reactive protein are elevated, as well as levels of lactate dehydrogenase, IL-18, aspartate transaminase, and alanine transaminase. The exact pathogenesis of fulminant MPP remains unclear, but theories include a delayed hypersensitivity reaction to M. pneumoniae and the contribution of delayed antibiotic administration to disease progression. Treatment options involve pairing the appropriate anti-mycoplasma agent with a corticosteroid that will downregulate the hypersensitivity response, and mortality rates are quite low in this treatment group. Further research is necessary to determine the exact pathogenesis of severe and fulminant types of MPP. PMID:27313568

  16. AB129. Osteogenesis imperfecta: clinical features and bisphosphonate treatment outcome

    PubMed Central

    Can, Ngoc Thi Bich; Vu, Dung Chi; Bui, Thao Phuong; Nguyen, Khanh Ngoc

    2015-01-01

    Background and objective Osteogenesis imperfecta (OI) comprises a group of disorders principally affecting type I collagen which result in increased bone fragility. Children with severe OI suffer recurrent fractures, resulting in severe deformity and growth stunting in many cases, with loss of independent ambulation by the teenage years in over 50% of cases. Recently, cyclical intravenous treatment with pamidronate has proven of benefit to children with severe forms of OI. This article aims to describle clinical features and laboratory manifestations of patient with OI and evaluate outcome of bisphosphonate management. Methods Clinical features, biochemical finding, and management outcome of 104 cases were study. The patients were classified into four major subtypes of Sillience et al. 1979. Patients with severe types were treatment with pamidronate (Aredia) used Rauch protocol 2003. Results Now we have 196 patients (87 females and 109 males) but we studied focus on 104 patients from 98 families (60 males, 44 females) onset at 2.1±3.0 years (median 0.35) with the average fracture bone of 5.9±4.4 times. In there, 17% type I, 8% type II, 63% type III, and 12% type IV. Clinical features include of intrauterine fracture visible on ultrasound 35%, bone deformation after birth 68%, triangle face 76%, long bone deformation 91%, chest deformation 46%, scoliosis 27%, short status 90%, blue sclera 83%, dentinogenesis imperfecta 20%, hearing loss 6%. Thirty patients have been treated with pamidronate at 3.2±3.7 years (4 months to 8 years) during 13±0.8 months (6-30 months). Fourteen patients had fracture bone after 6 months of treatment but no patients had fracture bone after 12 months. Seven patients had been treatment after 1.6±0.5 years, BMD increase from 0.39±0.311 to 0.79±0.105 g/cm2 (P<0.05). One patient had fever reaction after first pamidronate infusion but controlled with standard antipyretic therapy, and do not recur in later treatments. Conclusions OI has

  17. Gender effect on clinical features of achalasia: a prospective study

    PubMed Central

    Mikaeli, Javad; Farrokhi, Farnoosh; Bishehsari, Faraz; Mahdavinia, Mahboobeh; Malekzadeh, Reza

    2006-01-01

    Background Achalasia is a well-characterized esophageal motor disorder but the rarity of the disease limits performing large studies on its demographic and clinical features. Methods Prospectively, 213 achalasia patients (110 men and 103 women) were enrolled in the study. The diagnosis established by clinical, radiographic, and endoscopic as well as manometry criteria. All patients underwent a pre-designed clinical evaluation before and within 6 months after the treatment. Results Solid dysphagia was the most common clinical symptom in men and women. Chest pain was the only symptom which was significantly different between two groups and was more complained by women than men (70.9% vs. 54.5% P value= 0.03). Although the occurrence of chest pain significantly reduced after treatment in both groups (P < 0.001), it was still higher among women (32% vs. 20.9% P value= 0.04). In both sexes, chest pain did not relate to the symptom duration, LES pressure and type of treatment patients received. Also no significant relation was found between chest pain and other symptoms expressed by men and women before and after treatment. Chest pain was less frequently reported by patients over 56 yrs of age in comparison to those less than 56 yrs (p < 0.05). Conclusion It seems that chest pain is the distinct symptom of achalasia which is affected by sex as well as age and does not relate to the duration of illness, LESP and the type of treatment achalasia patients receive. PMID:16579859

  18. Production and clinical development of nanoparticles for gene delivery

    PubMed Central

    Chen, Jie; Guo, Zhaopei; Tian, Huayu; Chen, Xuesi

    2016-01-01

    Gene therapy is a promising strategy for specific treatment of numerous gene-associated human diseases by intentionally altering the gene expression in pathological cells. A successful clinical application of gene-based therapy depends on an efficient gene delivery system. Many efforts have been attempted to improve the safety and efficiency of gene-based therapies. Nanoparticles have been proved to be the most promising vehicles for clinical gene therapy due to their tunable size, shape, surface, and biological behaviors. In this review, the clinical development of nanoparticles for gene delivery will be particularly highlighted. Several promising candidates, which are closest to clinical applications, will be briefly reviewed. Then, the recent developments of nanoparticles for clinical gene therapy will be identified and summarized. Finally, the development of nanoparticles for clinical gene delivery in future will be prospected. PMID:27088105

  19. Ocular features in Alport syndrome: pathogenesis and clinical significance.

    PubMed

    Savige, Judy; Sheth, Shivanand; Leys, Anita; Nicholson, Anjali; Mack, Heather G; Colville, Deb

    2015-04-01

    Alport syndrome is an inherited disease characterized by progressive renal failure, hearing loss, and ocular abnormalities. Mutations in the COL4A5 (X-linked), or COL4A3 and COL4A4 (autosomal recessive) genes result in absence of the collagen IV α3α4α5 network from the basement membranes of the cornea, lens capsule, and retina and are associated with corneal opacities, anterior lenticonus, fleck retinopathy, and temporal retinal thinning. Typically, these features do not affect vision or, in the case of lenticonus, are correctable. In contrast, the rarer ophthalmic complications of posterior polymorphous corneal dystrophy, giant macular hole, and maculopathy all produce visual loss. Many of the ocular features of Alport syndrome are common, easily recognizable, and thus, helpful diagnostically, and in identifying the likelihood of early-onset renal failure. Lenticonus and central fleck retinopathy strongly suggest the diagnosis of Alport syndrome and are associated with renal failure before the age of 30 years, in males with X-linked disease. Sometimes, ophthalmic features suggest the mode of inheritance. A peripheral retinopathy in the mother of a male with hematuria suggests X-linked inheritance, and central retinopathy or lenticonus in a female means that recessive disease is likely. Ocular examination, retinal photography, and optical coherence tomography are widely available, safe, fast, inexpensive, and acceptable to patients. Ocular examination is particularly helpful in the diagnosis of Alport syndrome when genetic testing is not readily available or the results are inconclusive. It also detects complications, such as macular hole, for which new treatments are emerging. PMID:25649157

  20. Clinical and Molecular Features of POLG-Related Mitochondrial Disease

    PubMed Central

    Stumpf, Jeffrey D.; Saneto, Russell P.; Copeland, William C.

    2013-01-01

    The inability to replicate mitochondrial genomes (mtDNA) by the mitochondrial DNA polymerase (pol γ) leads to a subset of mitochondrial diseases. Many mutations in POLG, the gene that encodes pol γ, have been associated with mitochondrial diseases such as myocerebrohepatopathy spectrum (MCHS) disorders, Alpers-Huttenlocher syndrome, myoclonic epilepsy myopathy sensory ataxia (MEMSA), ataxia neuropathy spectrum (ANS), and progressive external ophthalmoplegia (PEO). This chapter explores five important topics in POLG-related disease: (1) clinical symptoms that identify and distinguish POLG-related diseases, (2) molecular characterization of defects in polymerase activity by POLG disease variants, (3) the importance of holoenzyme formation in disease presentation, (4) the role of pol γ exonuclease activity and mutagenesis in disease and aging, and (5) novel approaches to therapy and avoidance of toxicity based on primary research in pol γ replication. PMID:23545419

  1. Myhre syndrome: Clinical features and restrictive cardiopulmonary complications.

    PubMed

    Starr, Lois J; Grange, Dorothy K; Delaney, Jeffrey W; Yetman, Anji T; Hammel, James M; Sanmann, Jennifer N; Perry, Deborah A; Schaefer, G Bradley; Olney, Ann Haskins

    2015-12-01

    Myhre syndrome, a connective tissue disorder characterized by deafness, restricted joint movement, compact body habitus, and distinctive craniofacial and skeletal features, is caused by heterozygous mutations in SMAD4. Cardiac manifestations reported to date have included patent ductus arteriosus, septal defects, aortic coarctation and pericarditis. We present five previously unreported patients with Myhre syndrome. Despite varied clinical phenotypes all had significant cardiac and/or pulmonary pathology and abnormal wound healing. Included herein is the first report of cardiac transplantation in patients with Myhre syndrome. A progressive and markedly abnormal fibroproliferative response to surgical intervention is a newly delineated complication that occurred in all patients and contributes to our understanding of the natural history of this disorder. We recommend routine cardiopulmonary surveillance for patients with Myhre syndrome. Surgical intervention should be approached with extreme caution and with as little invasion as possible as the propensity to develop fibrosis/scar tissue is dramatic and can cause significant morbidity and mortality. PMID:26420300

  2. Epidemiology, pathophysiology, and clinical features of obstructive sleep apnea.

    PubMed

    Madani, Mansoor; Madani, Farideh

    2009-11-01

    The normal cycle of respiration includes a unique balancing force between many upper airway structures that control its dilation and closure. Alteration of this delicate equilibrium, possibly by an increased airflow resistance, can cause various degrees of obstructive sleep apnea (OSA). OSA is now recognized as a major illness, an important cause of medical morbidity and mortality affecting millions of people worldwide, and a major predisposing factor for several systemic conditions, such as hypertension, cardiovascular disease, stroke, diabetes, and even sexual dysfunction. Initial evaluation for possible OSA may be done by dental professionals who can provide guidance for its comprehensive evaluation and management. Because of the complexity of the disease, factors contributing to its development must be identified. Some factors caused by the patient's anatomic structures are slightly easier to rectify, whereas others may relate to the patient's age, sex, habits, or associated illnesses, including obesity. In this article, various epidemiologic, pathophysiologic, and clinical features of OSA are discussed. PMID:19944337

  3. Update on Mastocytosis (Part 1): Pathophysiology, Clinical Features, and Diagnosis.

    PubMed

    Azaña, J M; Torrelo, A; Matito, A

    2016-01-01

    Mastocytosis is a term used to describe a heterogeneous group of disorders characterized by clonal proliferation of mast cells in various organs. The organ most often affected is the skin. Mastocytosis is a relatively rare disorder that affects both sexes equally. It can occur at any age, although it tends to appear in the first decade of life, or later, between the second and fifth decades. Our understanding of the pathophysiology of mastocytosis has improved greatly in recent years, with the discovery that somatic c-kit mutations and aberrant immunophenotypic features have an important role. The clinical manifestations of mastocytosis are diverse, and skin lesions are the key to diagnosis in most patients. PMID:26546030

  4. Hyperprolactinemia in children: clinical features and long-term results.

    PubMed

    Catli, Gonul; Abaci, Ayhan; Altincik, Ayca; Demir, Korcan; Can, Sule; Buyukgebiz, Atilla; Bober, Ece

    2012-01-01

    Hyperprolactinemia is a rare endocrine disorder in childhood, which may result from hypophyseal adenoma. We aimed to review the etiologic reasons and clinical features in hyperprolactinemia patients retrospectively. The mean age of 11 female patients at diagnosis was 14.2 ± 1.3 years. Five patients had microadenoma, four patients had macroadenoma, and two patients were diagnosed with idiopathic hyperprolactinemia. The most frequent symptoms were menstrual disorders, headache, and galactorrhea, and one-third of the patients had obesity at diagnosis. There was no anterior pituitary hormone deficiency. All patients received bromocriptine as initial therapy; only two patients with macroadenoma and one patient with microadenoma were switched to cabergoline. Transsphenoidal surgery was performed for a patient with macroadenoma, who had cavernous sinus invasion and visual field defect. Medical treatment should be the first-line treatment option in both microadenoma and macroadenoma cases without any neurological signs. Surgery should be employed with limited indications. PMID:23329759

  5. Clinical Features and Awareness of Hand Eczema in Korea

    PubMed Central

    Park, Jae Beom; Lee, Seung Ho; Kim, Kea Jeung; Lee, Ga-Young; Yang, Jun-Mo; Kim, Do Won; Lee, Seok Jong; Lee, Cheol Heon; Park, Eun Joo; Kim, Kyu Han; Eun, Hee Chul; Chang, Sung Eun; Moon, Kee Chan; Kim, Seong Hyun; Kim, Seong Jin; Kim, Byung-Soo; Lee, Jun Young; Kim, Hyung-Ok; Kang, Hoon; Lee, Min Geol; Kim, Soo-Chan; Ro, Young Suck; Ko, Joo Yeon; Park, Mi Youn; Kim, Myung Hwa; Shin, Jeong Hyun; Choi, Hae Young; Hong, Chang Kwun; Lee, Sung Yul; Bak, Hana

    2016-01-01

    Background Hand eczema is one of the most common skin disorders and negatively affects quality of life. However, a large-scale multicenter study investigating the clinical features of patients with hand eczema has not yet been conducted in Korea. Objective To identify the prevalence of various hand diseases, which is defined as all cutaneous disease occurring in hands, and to investigate the clinical features of patients with hand eczema and the awareness about hand eczema in the general population and to compare the prevalence of hand eczema between health care providers and non-health care providers. Methods To estimate the prevalence of hand diseases, we analyzed the medical records of patients from 24 medical centers. Patients were assessed by online and offline questionnaires. A 1,000 from general population and 913 hand eczema patients answered the questionnaire, for a total of 1,913 subjects. Results The most common hand disease was irritant contact dermatitis. In an online survey, the lifetime prevalence of hand eczema was 31.2%. Hand eczema was more likely to occur in females (66.0%) and younger (20~39 years, 53.9%). Health care providers and housewives were the occupations most frequently associated with hand eczema. Winter (33.6%) was the most common season which people experienced aggravation. The 63.0% and 67.0% answered that hand eczema hinders their personal relationship and negatively affects daily living activities, respectively. Conclusion Hand eczema is a very common disease and hinders the quality of life. The appropriate identification of hand eczema is necessary to implement effective and efficient treatment. PMID:27274632

  6. Clinical features of allergic bronchopulmonary aspergillosis in Korea.

    PubMed

    Kim, Joo-Hee; Jin, Hyun Jung; Nam, Young-Hee; Hwang, Eui-Kyung; Ye, Young-Min; Park, Hae-Sim

    2012-09-01

    Allergic bronchopulmonary aspergillosis (ABPA) is a complex disease, triggered by a hypersensitivity reaction to the allergen Aspergillus fumigatus. This disease occurs frequently in patients with cystic fibrosis and severe asthma in Western countries, with a prevalence of 2%-15%. However, there have been only a few case reports in Korea. We investigated the clinical and immunological features of patients with ABPA. Ten adult patients diagnosed with ABPA, according to Greenberger's criteria, were analyzed during the period January 2001 to December 2010 in a tertiary hospital. Skin-prick tests, pulmonary function tests, and high-resolution computed tomography (HRCT) were performed, and total serum IgE and A. fumigatus-specific IgE were measured. The patient cohort consisted of men who were middle-aged (median, 62.5; range, 19.0-79.0 years) at the diagnosis of ABPA with a long duration of asthma (median, 15.0; range, 1-48 years). Approximately 40% of the patients had a history of pulmonary tuberculosis more than 10 years prior to the study (median 23.5; range, 10.0-31.0 years) accompanied by severe obstructive lung function and radiological post-tuberculous destructive lung lesions. These patients also tended to have increased levels of immunologic parameters, such as total eosinophil count, total IgE, and A. fumigates-specific IgE, compared to those without tuberculosis sequels. Two patients with steroid-dependent asthma were treated with anti-IgE therapy and showed good responses. We report the clinical features of 10 ABPA patients, including 4 with histories of post-tuberculosis destructive lesions. Furthermore, anti-IgE antibody therapy may be an alternative strategy in cases of steroid-dependent ABPA. PMID:22950037

  7. Hairy cell leukemia: clinical features and therapeutic advances.

    PubMed

    Lembersky, B C; Golomb, H M

    1987-01-01

    Hairy cell leukemia (HCL) is a rare chronic lymphoproliferative disorder which has been extensively studied over the past decade. Much has been learned regarding the diagnosis, natural history, biology, and treatment of this unique neoplasm. The disease most commonly affects middle aged men and characteristic clinical features include splenomegaly, cytopenias, and usually the presence in the peripheral blood of distinctive 'hairy cells' with irregular cytoplasmic projections. Diagnosis can usually be confirmed by bone marrow biopsy. Although the natural history can be extremely variable among patients, complications are usually referable to the cytopenias, with anemia and infection being most frequent. In addition to pyogenic infections, patients are susceptible to unusual organisms including atypical mycobacterium, legionella, and fungi. The requirement of red blood cell transfusion, severe granulocytopenia or thrombocytopenia, frequent infections, or painful splenomegaly are all indications for treatment. Splenectomy is the standard initial treatment of choice. However, in the past few years there have been exciting major advances in the therapeutic modalities for HCL. Recombinant alpha-interferon is highly effective, with beneficial responses occurring in close to 90% of patients. The Food and Drug Administration has recently approved the use of interferon for HCL. This represents the first time a biological response modifier has been approved for the treatment of human disease. In addition, preliminary results with the adenosine deaminase inhibitor, 2'deoxycoformycin (dcf), have been encouraging. Further clinical trials are required in order to determine the optimal sequential treatment strategy for HCL. The exact mechanisms of action of both interferon and dcf in HCL remain to be elucidated. A better understanding of the unusual features of the hairy cell and the underlying biological effect of these two agents in HCL may have important applications in other

  8. Factors Associated with Clinical and Topographical Features of Laryngeal Tuberculosis

    PubMed Central

    Reis, João Gustavo Corrêa; Reis, Clarissa Souza Mota; da Costa, Daniel César Silva; Lucena, Márcia Mendonça; Schubach, Armando de Oliveira; Oliveira, Raquel de Vasconcellos Carvalhaes; Rolla, Valéria Cavalcanti; Conceição-Silva, Fátima; Valete-Rosalino, Cláudia Maria

    2016-01-01

    Introduction Laryngeal tuberculosis (LTB) is the most frequent granulomatous disease of the larynx and represents less than 2% of extrapulmonary TB cases. There are no pathognomonic clinical and endoscopic features of this disease and studies on LTB that can assist in its diagnostic characterization are lacking. Objective To identify factors associated with clinical and topographical features of LTB. Method a retrospective cross-sectional study was conducted from the medical records of 36 patients with confirmed LTB diagnosis. Results Dysphonia and cough were the main symptoms presented by patients and the true vocal folds the most frequently affected site. The average of the duration of the disease evolution was significantly higher in patients with dysphonia than in patients without this symptom. We observed association between dysphonia and true vocal fold lesions and between odynophagia and lesions in the epiglottis, arytenoids and aryepiglottic folds. Odynophagia was more frequent in individuals with lesions in four or more laryngeal sites. Weight loss equal or above 10% of the body weight was more frequent in patients with odynophagia as first symptom and in patients with ulcerated lesion. Dyspnea on exertion was more frequent in individuals with more extensive laryngeal lesions. The percentage of smokers with lesions in four or more laryngeal sites was greater than that found in non-smokers. Laryngeal tissue fragment bacilloscopy and culture examinations were less positive than sputum ones. Conclusions Smoking appears to be associated with the development of more extensive LTB lesions, and LTB with dyspnea on exertion and odynophagia with consequent impairment of nutritional status. We emphasize the need for histopathologic confirmation, once positive sputum bacteriological examinations seem not to necessarily reflect laryngeal involvement. PMID:27077734

  9. Clinical features of pedophilia and implications for treatment.

    PubMed

    Cohen, Lisa J; Galynker, Igor I

    2002-09-01

    The authors discuss the diagnostic criteria for pedophilia and review the literature on its clinical features, including data on prevalence, gender, age of onset, number of victims, frequency and type of acts, violence, impulsivity, and insight. Findings concerning the characteristics of victims (e.g., sex, age, relationship to the pedophile) and research on pedophilic subtypes-exclusive versus nonexclusive; incestuous versus nonincestuous; heterosexual, homosexual, or bisexual-are reviewed. Studies have shown that pedophiles may share many psychiatric features beyond deviant sexual desire, including high rates of comorbid axis I disorders (affective disorders, substance use disorders, impulse control disorders, other paraphilias) as well as severe axis II psychopathology (especially antisocial and Cluster C personality disorders). The authors present several possible etiological models for pedophilia and conclude that further research is needed concerning the etiological role of a childhood history of sexual abuse as well as the underlying neurobiology of deviant sexual arousal and decreased erotic differentiation. Finally, findings concerning pharmacological and cognitive-behavioral treatments for pedophilia are briefly reviewed. Recidivism, drop-out, and noncompliance are significant problems in the treatment of pedophilia. The authors review predictors of treatment outcome and conclude that pedophilia is extremely difficult to treat and that effective treatment needs to be intensive, long-term, and comprehensive, possibly with lifetime follow-up. PMID:15985890

  10. Dermoscopic and clinical features of head and neck melanoma*

    PubMed Central

    Cengiz, Fatma Pelin; Cengiz, Abdurrahman Bugra; Emiroglu, Nazan; Comert, Ela; Wellenhof, Rainer Hofmann

    2015-01-01

    BACKGROUND The dermoscopic criteria of extrafacial melanomas are well-known. OBJECTIVE To determine the frequency of dermatoscopic findings in head and neck melanomas (HNM) and to assess the distinguishing dermoscopic criteria of facial and extrafacial melanoma. METHODS This observational study included 108 patients with HNM (63% male, mean age 64 years). Participants underwent individual dermoscopic imaging of clinically melanoma. All lesions were excised, and histopathological examination was performed on all specimens. RESULTS Drawing on histopathological analysis, lentigo maligna melanoma or lentigo maligna was diagnosed in 60 lesions, superficial spreading melanoma in 18, nodular in 10, desmoplastic in 8, superficial spreading melanoma in situ in 12. The most frequent location for head and neck melanoma was the cheek (60 patients, 55.6%). Eight prominent dermatoscopic features were observed in facial melanoma: annular-granular pattern (18%); rhomboidal structures (29%); pseudonetwork (29%); asymmetrical, pigmented, follicular openings (51%); obliterated hair follicles (8%); red rhomboidal structures (18%); increased density of the vascular network (32%); scar-like depigmentation (59%). CONCLUSIONS HNM has specific dermoscopic features, and classical extrafacial dermoscopic rules are less useful for diagnosis of facial melanoma. In our study, further characteristic dermatoscopic findings were detected in facial melanoma such as low frequencies of irregular dots, 2 or fewer colors in lesions, the presence of pseudonetwork, increased density of the vascular network, red rhomboidal structures, in addition to dermatoscopic findings of extrafacial melanoma. Thus, it is concluded that the prediction and identification of HNM may be evident with the help of these signs. PMID:26375217

  11. Clinical features of spinal and bulbar muscular atrophy

    PubMed Central

    Rhodes, Lindsay E.; Freeman, Brandi K.; Auh, Sungyoung; Kokkinis, Angela D.; La Pean, Alison; Chen, Cheunju; Lehky, Tanya J.; Shrader, Joseph A.; Levy, Ellen W.; Harris-Love, Michael; Di Prospero, Nicholas A.

    2009-01-01

    Spinal and bulbar muscular atrophy is an X-linked motor neuron disease caused by a CAG repeat expansion in the androgen receptor gene. To characterize the natural history and define outcome measures for clinical trials, we assessed the clinical history, laboratory findings and muscle strength and function in 57 patients with genetically confirmed disease. We also administered self-assessment questionnaires for activities of daily living, quality of life and erectile function. We found an average delay of over 5 years from onset of weakness to diagnosis. Muscle strength and function correlated directly with serum testosterone levels and inversely with CAG repeat length, age and duration of weakness. Motor unit number estimation was decreased by about half compared to healthy controls. Sensory nerve action potentials were reduced in nearly all subjects. Quantitative muscle assessment and timed 2 min walk may be useful as meaningful indicators of disease status. The direct correlation of testosterone levels with muscle strength indicates that androgens may have a positive effect on muscle function in spinal and bulbar muscular atrophy patients, in addition to the toxic effects described in animal models. PMID:19846582

  12. Clinical features and treatment of endophthalmitis after cataract surgery.

    PubMed

    Zhu, J; Li, Z H

    2015-01-01

    The aim of this study was to investigate the clinical features and treatment results of endophthalmitis after cataract surgery. Five patients with endophthalmitis after phacoemulsification with intraocular lens implantation were enrolled in this study. The pathogenesis, clinical manifestation, and surgical outcomes of 5 patients were compared. Three patients were surgically treated with anterior chamber irrigation and vitrectomy with intravitreal injection. The remaining two patients were medically treated with an intravitreal injection of vancomycin and ceftazidime. Treatment results of the five patients were analyzed. Four patients had positive cultures for bacteria (two cases Staphylococcus epidermidis, one case Enterococcus faecalis, and one case head-like Staphylococcus). The culture of the fifth patient did not have bacterial growth. One year following treatment, four patients had restored visual acuity and a clear vitreous cavity. Retinal detachment and other complications were not observed. The remaining patient had a visual acuity of index at 30 cm one year following treatment. For patients with endophthalmitis after cataract surgery, a biochemical laboratory examination should be promptly performed and should include a bacterial culture and drug sensitivity test. When necessary, vitrectomy combined with an intravitreal injection of vancomycin should be performed to treat the infection early and to help retain useful vision. PMID:26125869

  13. Clinical features of schizophrenia with enhanced carbonyl stress.

    PubMed

    Miyashita, Mitsuhiro; Arai, Makoto; Kobori, Akiko; Ichikawa, Tomoe; Toriumi, Kazuya; Niizato, Kazuhiro; Oshima, Kenichi; Okazaki, Yuji; Yoshikawa, Takeo; Amano, Naoji; Miyata, Toshio; Itokawa, Masanari

    2014-09-01

    Accumulating evidence suggests that advanced glycation end products, generated as a consequence of facilitated carbonyl stress, are implicated in the development of a variety of diseases. These diseases include neurodegenerative illnesses, such as Alzheimer disease. Pyridoxamine is one of the 3 forms of vitamin B6, and it acts by combating carbonyl stress and inhibiting the formation of AGEs. Depletion of pyridoxamine due to enhanced carbonyl stress eventually leads to a decrease in the other forms of vitamin B6, namely pyridoxal and pyridoxine. We previously reported that higher levels of plasma pentosidine, a well-known biomarker for advanced glycation end products, and decreased serum pyridoxal levels were found in a subpopulation of schizophrenic patients. However, there is as yet no clinical characterization of this subset of schizophrenia. In this study, we found that these patients shared many clinical features with treatment-resistant schizophrenia. These include a higher proportion of inpatients, low educational status, longer durations of hospitalization, and higher doses of antipsychotic medication, compared with patients without carbonyl stress. Interestingly, psychopathological symptoms showed a tendency towards negative association with serum vitamin B6 levels. Our results support the idea that treatment regimes reducing carbonyl stress, such as supplementation of pyridoxamine, could provide novel therapeutic benefits for this subgroup of patients. PMID:24062594

  14. Flavimonas oryzihabitans bacteremia: clinical features and microbiological characteristics of isolates.

    PubMed

    Lin, R D; Hsueh, P R; Chang, J C; Teng, L J; Chang, S C; Ho, S W; Hsieh, W C; Luh, K T

    1997-05-01

    Flavimonas oryzihabitans is rarely reported as a pathogen in humans. Twelve cases of F. oryzihabitans bacteremia were diagnosed at National Taiwan University Hospital over a 3-year period. The clinical features of these patients were analyzed, and antimicrobial susceptibilities and random amplified polymorphic DNA (RAPD) patterns of the 12 isolates were studied. Among these 12 patients, eight (67%) had underlying neoplastic diseases and all acquired F. oryzihabitans bacteremia while hospitalized. The clinical syndromes included primary bacteremia in 5 patients (42%), biliary tract infection in 3 (25%), and peritonitis, subdural empyema, infusion-related bacteremia, and pneumonia in 1 each. Polymicrobial bacteremia or concomitant fungemia was seen in three patients (25%). All the patients survived after antibiotic treatment. All isolates were susceptible to piperacillin, third-generation cephalosporins, aminoglycosides, and quinolones but resistant to cephalothin, cefuroxime, and trimethoprim. Susceptibility to aztreonam was variable (25%). The RAPD patterns differed among the isolates, indicating the epidemiological unrelatedness of these infections. F. oryzihabitans should be included as an etiology of severe nosocomial infection in patients with underlying debilitating diseases. PMID:9142784

  15. A unified concept of idiopathic orofacial pain: clinical features.

    PubMed

    Woda, A; Pionchon, P

    1999-01-01

    The main features of atypical facial pain, stomatodynia, atypical odontalgia, and masticatory muscle and temporomandibular joint (TMJ) disorders are compared in this article, which included a search of articles indexed in MEDLINE. The fact that their terminology has been the subject of many debates can be considered a consequence of taxonomic difficulties and uncertainties. Epidemiologic studies indicate marked female predominance for all types of idiopathic orofacial pain. There is also a difference in the age of maximal prevalence between masticatory muscle and TMJ disorders and the other entities. The clinical presentations display several symptoms in common. Pain is oral, perioral, or facial and does not follow a nervous pathway. It has been present for the last 4 to 6 months or has returned periodically in the same form over a period of several months or years. The pain is continuous, has no major paroxysmal character, and is present throughout all or part of the day. It is generally absent during sleep. Clinical, radiographic, or laboratory examination does not reveal any obvious organic cause of pain. There is also a frequent presence of certain psychologic factors, personality traits, or life events. Based on these shared characteristics, a unified concept is proposed. Each of these entities belongs to a group of idiopathic orofacial pain and could be expressed in either the jaws, the buccal mucosa, the teeth, the masticatory muscles, or the TMJ. PMID:10823031

  16. Clinical features of endemic community-acquired psittacosis.

    PubMed

    Branley, J M; Weston, K M; England, J; Dwyer, D E; Sorrell, T C

    2014-01-01

    Following a large outbreak of community-acquired psittacosis in 2002 in residents of the Blue Mountains, New South Wales, Australia, we reviewed new cases in this area over a 7-year period from 2003 to 2009. Using the 2010 criteria from the Centers for Disease Control National Notifiable Diseases Surveillance System, 85 patients with possible psittacosis were identified, of which 48 were identified as definite or probable infection. Clinical features of these cases are summarized. In addition to Chlamydia-specific serology, specimens, where available, underwent nucleic acid testing for chlamydial DNA using real-time PCR. Chlamydophila psittaci DNA was detected in samples from 23 patients. Four of 18 specimens were culture positive. This is the first description of endemic psittacosis, and is characterized in this location by community-acquired psittacosis resulting from inadvertent exposure to birds. The disease is likely to be under-diagnosed, and may often be mistaken for gastroenteritis or meningitis given the frequency of non-respiratory symptoms, particularly without a history of contact with birds. Clinical characteristics of endemic and outbreak-associated cases were similar. The nature of exposure, risk factors and reasons for the occurrence of outbreaks of psittacosis require further investigation. PMID:25356332

  17. Clinical Features and Patient Management of Lujo Hemorrhagic Fever

    PubMed Central

    Sewlall, Nivesh H.; Richards, Guy; Duse, Adriano; Swanepoel, Robert; Paweska, Janusz; Blumberg, Lucille; Dinh, Thu Ha; Bausch, Daniel

    2014-01-01

    Background In 2008 a nosocomial outbreak of five cases of viral hemorrhagic fever due to a novel arenavirus, Lujo virus, occurred in Johannesburg, South Africa. Lujo virus is only the second pathogenic arenavirus, after Lassa virus, to be recognized in Africa and the first in over 40 years. Because of the remote, resource-poor, and often politically unstable regions where Lassa fever and other viral hemorrhagic fevers typically occur, there have been few opportunities to undertake in-depth study of their clinical manifestations, transmission dynamics, pathogenesis, or response to treatment options typically available in industrialized countries. Methods and Findings We describe the clinical features of five cases of Lujo hemorrhagic fever and summarize their clinical management, as well as providing additional epidemiologic detail regarding the 2008 outbreak. Illness typically began with the abrupt onset of fever, malaise, headache, and myalgias followed successively by sore throat, chest pain, gastrointestinal symptoms, rash, minor hemorrhage, subconjunctival injection, and neck and facial swelling over the first week of illness. No major hemorrhage was noted. Neurological signs were sometimes seen in the late stages. Shock and multi-organ system failure, often with evidence of disseminated intravascular coagulopathy, ensued in the second week, with death in four of the five cases. Distinctive treatment components of the one surviving patient included rapid commencement of the antiviral drug ribavirin and administration of HMG-CoA reductase inhibitors (statins), N-acetylcysteine, and recombinant factor VIIa. Conclusions Lujo virus causes a clinical syndrome remarkably similar to Lassa fever. Considering the high case-fatality and significant logistical impediments to controlled treatment efficacy trials for viral hemorrhagic fever, it is both logical and ethical to explore the use of the various compounds used in the treatment of the surviving case reported here

  18. Clinical features of Crohn disease concomitant with ankylosing spondylitis

    PubMed Central

    Liu, Song; Ding, Jie; Wang, Meng; Zhou, Wanqing; Feng, Min; Guan, Wenxian

    2016-01-01

    Abstract Extraintestinal manifestations (EIMs) cause increased morbidity and decreased quality of life in Crohn disease (CD). Ankylosing spondylitis (AS) belongs to EIMs. Very little is known on the clinical features of CD concomitant with AS. This study is to investigate the clinical features of CD patients with AS. We retrospectively collected all CD patients with AS in our hospital, and established a comparison group (CD without AS) with age, sex, and duration of Crohn disease matched. Clinical information was retrieved for comparison. Eight CD + AS patients were identified from 195 CD patients. Sixteen CD patients were randomly selected into comparison group. All CD + AS patients were male, HLA-B27 (+), and rheumatoid factor (−) with an average age of 40.8 ± 4.52 years. Significant correlation between disease activity of CD and AS was revealed (r = 0.857, P = 0.011). Significant correlation between disease activity of CD and functional limitation associated with AS was identified (r = 0.881, P < 0.01). C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and globulin were positively correlated to Crohn disease activity index (CDAI), Bath AS disease activity index, and Bath AS functional index(BASFI) scores (r = 0.73–0.93, P < 0.05). Albumin was negatively associated with CDAI and BASFI (r = −0.73 to −0.91, P < 0.05). The ratio of albumin to globulin (Alb/Glo) was significantly related to all 3 scores (r = −0.81 to −0.91, P < 0.05). Male predominance with a 4.12% concomitant incidence of AS is observed in CD patients. Disease activity of CD correlates with disease activity of AS and functional limitation caused by AS. CRP, ESR, and Alb/Glo may serve as biomarkers for disease activity and functional limitation in CD patients concomitant with AS, although future studies are expected. PMID:27428240

  19. Amebic liver abscess: epidemiology, clinical features, and outcome.

    PubMed Central

    Seeto, R K; Rockey, D C

    1999-01-01

    Amebic liver abscess (ALA) is a serious, but readily treatable form of hepatic infection. In order to understand the clinical features of this condition in the United States, we reviewed the medical histories of 56 patients with ALA at two large San Francisco Hospitals from 1979 to 1994. Patients were divided into the following groups based on the presumed manner in which they had acquired ALA: those born or raised in the United States, with a history of travel to an endemic area (Tr-ALA); those from an endemic area, but living in the United States for less than one year (En-ALA); and those neither from nor having traveled to an endemic area (N-ALA). We found distinct clinical patterns in patients from different epidemiological groups. Patients with Tr-ALA were a decade older than those from endemic regions, were more likely to be male, and tended to have an insidious onset. Furthermore, compared to patients with En-ALA, those with Tr-ALA were more likely to have hepatomegaly (P < 0.0001) and large abscesses (ALA > 10 cm; P < 0.01). One third of the patients studied had no associated travel history or endemic origin as risk factors. Of these, 63% had a condition consistent with severe immunosuppression, such as infection with the human immunodeficiency virus (HIV), malnourishment with severe hypoalbuminemia, or chronic infection. In patients with N-ALA, the presence of a presumed immunosuppressed state increased significantly, as compared to patients with endemic or travel risk factors for ALA. During the last five years of the study, one third of all patients diagnosed with ALA were HIV positive (including 2 with a new diagnosis of AIDS), many of whom were discovered to be HIV-infected only after presentation with ALA. We conclude that travel to and origin in an endemic area are important risk factors for the development of ALA, and patients in these different epidemiological groups appear to have distinct clinical features. Further, in the absence of recognized

  20. Malignant transformation in monostotic fibrous dysplasia: clinical features, imaging features, outcomes in 10 patients, and review.

    PubMed

    Qu, Nan; Yao, Weiwu; Cui, Xiaojiang; Zhang, Huizhen

    2015-01-01

    Malignant transformation in fibrous dysplasia (FD) is uncommon. The purpose of this study was to investigate clinical and imaging features, and outcomes of malignant transformation in monostotic FD.Data for 10 pathologically confirmed malignant transformations in monostotic FD from January 2005 to December 2013 were retrospectively reviewed. Patient data were recorded, and radiographs (n = 10), computed tomography (CT) (n = 5), magnetic resonance (MR) (n = 4), and bone scintigrams (n = 10) were evaluated for lesion location, margin, cortical destruction, marrow involvement, periosteal reaction, and soft tissue mass by 2 musculoskeletal radiologists with agreement by consensus. Clinical features, management, and prognosis were also analyzed for each of the 10 cases.There were 8 male and 2 female patients (mean age 46.5 ± 15.9 years). The affected sites were the femur (n = 4), humerus (n = 2), tibia (n = 3), and ilium (n = 1). Five cases had received previous surgery and 5 cases had no history of surgery. No patients had been given prior irradiation treatment. For the 5 cases with surgery, radiographs and CT showed purely osteolytic lesions with poor margination in the curettage area (n = 5), cortical destruction (n = 5), obvious soft tissue mass (n = 1), and mineralization (n = 2). For the 5 cases without surgery, radiographs and CT identified poorly marginated, osteolytic lesions within or near the area with "ground-glass" opacity (n = 4), cortical erosion (n = 4), and mineralization (n = 2). Magnetic resonance imaging (MRI) also identified lesions with heterogeneous signal intensity and pronounced enhancement. Bone scintigraphy revealed eccentric increased uptake of radionuclide in monostotic lesion (n = 10). Pathology reports revealed osteosarcoma (n = 7), fibrosarcoma (n = 2), and malignant fibrous histiocytoma (MFH) (n = 1). At the end of the study, 1 patient died from tumors, 1

  1. Currarino syndrome: variable imaging features in three siblings with HLXB9 gene mutation.

    PubMed

    Kim, Ah Yeong; Yoo, So-Young; Kim, Ji Hye; Eo, Hong; Jeon, Tae Yeon

    2013-01-01

    Currarino syndrome (CS) is characterized by the triad of partial sacral defect, anorectal malformation, and presacral mass and has been recently reported to be associated with mutations in the HLXB9 gene, which have been suggested to be the genetic background of CS. Phenotypic expression of the HLXB9 gene mutation in a CS family varies from an incomplete to a complete triad. We present variable clinical and imaging features of CS in three siblings with genetically identified HLXB9 mutation. Clinical presentation, management and outcome were also reviewed, and we suggest that magnetic resonance imaging should be used as a screening tool in the members of a CS family with genetic mutation in order to avoid morbidity and mortality from an undiagnosed presacral mass. PMID:23466002

  2. Heterogeneity in clinical features and disease severity in ataxia-associated SYNE1 mutations.

    PubMed

    Wiethoff, Sarah; Hersheson, Joshua; Bettencourt, Conceicao; Wood, Nicholas W; Houlden, Henry

    2016-08-01

    The autosomal recessive spinocerebellar ataxias are an exciting field of study, with a growing number of causal genes and an expanding phenotypic spectrum. SYNE1 was originally discovered in 2007 as the causal gene underlying autosomal recessive spinocerebellar ataxia 1, a disease clinically thought to manifest with mainly pure cerebellar ataxia. Since the original report SYNE1 mutations have also been identified in families with motor neuronopathy and arthrogryposis but few families have been screened as the gene is very large at 146 exons in length. We screened 196 recessive and sporadic ataxia patients for mutations in SYNE1 using next generation sequencing in order to assess its frequency and extend the clinicogenetic spectrum. We identified four novel truncating mutations spread throughout the SYNE1 gene from three families living in London that originated from England, Turkey and Sri Lanka. The phenotype was mainly pure cerebellar ataxia in two families, cognitive decline was present in all three families, axonal neuropathy in one family and marked spasticity in the Turkish family, with a range of disease severities. Searching for genotype-phenotype correlations in the SYNE1 gene, defects located near the 3' prime end of the gene are more frequently associated with motor neuron or neuromuscular involvement so far. Our data indicate SYNE1 mutations are not an uncommon cause of recessive ataxia with or without additional clinical features in patients from various ethnicities. The use of next generation sequencing allows the rapid analysis of large genes and will likely reveal more SYNE1 associated cases and further expand genotype-phenotype correlations. PMID:27178001

  3. Chromatin and epigenetic features of long-range gene regulation

    PubMed Central

    Harmston, Nathan; Lenhard, Boris

    2013-01-01

    The precise regulation of gene transcription during metazoan development is controlled by a complex system of interactions between transcription factors, histone modifications and modifying enzymes and chromatin conformation. Developments in chromosome conformation capture technologies have revealed that interactions between regions of chromatin are pervasive and highly cell-type specific. The movement of enhancers and promoters in and out of higher-order chromatin structures within the nucleus are associated with changes in expression and histone modifications. However, the factors responsible for mediating these changes and determining enhancer:promoter specificity are still not completely known. In this review, we summarize what is known about the patterns of epigenetic and chromatin features characteristic of elements involved in long-range interactions. In addition, we review the insights into both local and global patterns of chromatin interactions that have been revealed by the latest experimental and computational methods. PMID:23766291

  4. Spinal Neuroarthropathy: Pathophysiology, Clinical and Imaging Features, and Differential Diagnosis.

    PubMed

    Ledbetter, Luke N; Salzman, Karen L; Sanders, R Kent; Shah, Lubdha M

    2016-01-01

    Spinal neuroarthropathy (SNA), or Charcot spine, is a progressive destructive arthropathy occurring after loss of neuroprotective sensation and proprioceptive reflexes. Clinical diagnosis is difficult because of the variable length to presentation after initial neurologic damage and the limited symptoms given preexisting neurologic deficits. SNA is also a diagnostic challenge because its imaging features are similar to those of spinal conditions such as discitis-osteomyelitis, osseous tuberculosis, hemodialysis-related spondyloarthropathy, and pseudarthrosis. The most important imaging clues for diagnosis of SNA are involvement of both anterior and posterior elements at the thoracolumbar and lumbosacral junctions. Additional imaging clues include vacuum phenomenon within the disk (indicating excessive motion), malalignment, and paraspinal soft-tissue masses or fluid collections containing bone debris. Despite these imaging signs, findings may overlap in some cases with those of infection, or SNA can be superinfected, and biopsy may be necessary. Development of SNA requires a preexisting neurologic condition, most commonly traumatic spinal cord injury. Areas of greatest mobility and weight bearing within the desensate spine experience repetitive microtrauma and unregulated hyperemia, leading to destruction of the intervertebral articulations. The progressive and destructive nature of SNA causes substantial deformity, loss of function, and often further neurologic deficits. Patients present with deformity, back pain, audible noises during movement, or new neurologic symptoms. The mainstay of treatment is surgical débridement, reduction, and fusion. The radiologist can help initiate early intervention by using key imaging features to distinguish SNA from imaging mimics and prevent further neurologic deterioration. (©)RSNA, 2016. PMID:27058729

  5. Small Deletions of SATB2 Cause Some of the Clinical Features of the 2q33.1 Microdeletion Syndrome

    PubMed Central

    Rosenfeld, Jill A.; Ballif, Blake C.; Lucas, Ann; Spence, Edward J.; Powell, Cynthia; Aylsworth, Arthur S.; Torchia, Beth A.; Shaffer, Lisa G.

    2009-01-01

    Recurrent deletions of 2q32q33 have recently been reported as a new microdeletion syndrome. Clinical features of this syndrome include severe mental retardation, growth retardation, dysmorphic features, thin and sparse hair, feeding difficulties and cleft or high palate. The commonly deleted region contains at least seven genes. Haploinsufficiency of one of these genes, SATB2, a DNA-binding protein that regulates gene expression, has been implicated as causative in the cleft or high palate of individuals with 2q32q33 microdeletion syndrome. In this study we describe three individuals with smaller microdeletions of this region, within 2q33.1. The deletions ranged in size from 173.1 kb to 185.2 kb and spanned part of SATB2. Review of clinical records showed similar clinical features among these individuals, including severe developmental delay and tooth abnormalities. Two of the individuals had behavioral problems. Only one of the subjects presented here had a cleft palate, suggesting reduced penetrance for this feature. Our results suggest that deletion of SATB2 is responsible for several of the clinical features associated with 2q32q33 microdeletion syndrome. PMID:19668335

  6. Clinical Features and Outcomes of Pasteurella multocida Infection

    PubMed Central

    Giordano, Antonio; Dincman, Toros; Clyburn, Benjamin E.; Steed, Lisa L.; Rockey, Don C.

    2015-01-01

    Abstract Pasteurella multocida, a zoonotic infectious organism, has most often been described in patients after an animal bite. Here, we characterize the clinical features and outcomes of P multocida infection in a large cohort of patients according to the presence or absence of an animal bite. We retrospectively searched MUSC's laboratory information system for all patients with positive P multocida cultures from 2000 to 2014. Extensive data were abstracted, including clinical and outcome data. The Charlson comorbidity index (CCI) was used to assess comorbidities among patients. We identified 44 patients with P multocida infections, including 25 with an animal bite. The average age was 64 years and the majority of patients were women (N = 30). There was no difference in age and sex distribution among those with and without a bite (P = 0.38 and 0.75, respectively). A CCI ≥1 was significantly associated with the absence of a bite (P = 0.006). Patients presenting without a bite were more frequently bacteremic (37% vs 4%, respectively, P = 0.001), and were hospitalized more often (84% vs 44%, respectively, P = 0.012). Of the 8 patients who required intensive care unit (ICU)-based care, 7 were non-bite-related. There were 4 deaths, all occurring in patients not bitten. P multocida infections not associated with an animal bite were often associated with bacteremia, severe comorbidity(ies), immune-incompetent states, the need for ICU management, and were associated with substantial mortality. PMID:26356688

  7. Clinical Features of Newly Diagnosed Cytomegalovirus Retinitis in Northern Thailand

    PubMed Central

    Ausayakhun, Somsanguan; Keenan, Jeremy D; Ausayakhun, Sakarin; Jirawison, Choeng; Khouri, Claire M; Skalet, Alison H; Heiden, David; Holland, Gary N; Margolis, Todd P

    2011-01-01

    Purpose To characterize the clinical manifestations of cytomegalovirus (CMV) retinitis in northern Thailand. Design Prospective, observational cross-sectional study. Methods We recorded characteristics of 52 consecutive patients newly diagnosed with CMV retinitis at a tertiary university-based medical center in northern Thailand. Indirect ophthalmoscopy by experienced ophthalmologists was supplemented with fundus photography to determine the proportion of eyes with various clinical features of CMV retinitis. Results Of the 52 patients with CMV retinitis, 55.8% were female. All were HIV-positive. The vast majority (90.4%) had started antiretroviral therapy. CMV retinitis was bilateral in 46.2% of patients. Bilateral visual acuity worse than 20/60 was observed in 23.1% of patients. Of 76 eyes with CMV retinitis, 61.8% had zone I disease and 21.6% had lesions involving the fovea. Lesions larger than 25% of the retinal area were observed in 57.5% of affected eyes. CMV retinitis lesions commonly had marked or severe border opacity (47.4% of eyes). Vitreous haze was often present (46.1% of eyes). Visual impairment was more common in eyes with larger retinitis lesions. Retinitis lesion size, used as a proxy for duration of disease, was associated with fulminant appearance (OR 1.24 [1.01 – 1.51]), and marked or severe border opacity (OR 1.36 [1.11 – 1.67]). Based on lesion size, retinitis preceded antiretroviral treatment in each patient. Conclusions Patients presenting to a tertiary medical center in northern Thailand have advanced CMV retinitis, possibly due to delayed diagnosis. Earlier screening and treatment of CMV retinitis may limit progression of disease and prevent visual impairment in this population. PMID:22265148

  8. Growth factors from genes to clinical application

    SciTech Connect

    Sara, V.R. ); Hall, K.; Low, H. )

    1990-01-01

    The last decade has witnessed an explosion in the identification of growth factors and their receptors. This has been greatly facilitated by recombinant DNA technology, which has provided the tools not only to identify these proteins at the gene level but also to produce recombinant proteins for evaluating their biological activities. With the help of such techniques, we are moving toward an understanding of the biosynthesis of growth factors and their receptors, structure-function relationships, as well as mechanisms for intracellular signal transmission. The possibility of modifying these factors has opened new fields of clinical application. In this paper, four major areas of growth factor research are presented: the characterization of growth factor genes and their protein products, growth factor receptors and signal transduction by the receptors to mediate biological action, the biological actions of the various growth factors, and the role of growth factors in health and disease and their possible clinical application. Some of the topics covered include: structure of the IGFs and their variants; isoforms of PDGF receptor types; tyrosine kinase activation; structure of G-proteins in biological membranes; possible therapeutic application of NGF in the treatment of Parkinson's and Alzheimer's diseases; PDGF's possible role in the development of several fibroproliferative diseases and its therapeutic application in wound healing; and the possible use of angiogenic inhibitors in tumor treatment.

  9. Clinical, Epidemiologic, Histopathologic and Molecular Features of an Unexplained Dermopathy

    PubMed Central

    Pearson, Michele L.; Selby, Joseph V.; Katz, Kenneth A.; Cantrell, Virginia; Braden, Christopher R.; Parise, Monica E.; Paddock, Christopher D.; Lewin-Smith, Michael R.; Kalasinsky, Victor F.; Goldstein, Felicia C.; Hightower, Allen W.; Papier, Arthur; Lewis, Brian; Motipara, Sarita; Eberhard, Mark L.

    2012-01-01

    Background Morgellons is a poorly characterized constellation of symptoms, with the primary manifestations involving the skin. We conducted an investigation of this unexplained dermopathy to characterize the clinical and epidemiologic features and explore potential etiologies. Methods A descriptive study was conducted among persons at least 13 years of age and enrolled in Kaiser Permanente Northern California (KPNC) during 2006–2008. A case was defined as the self-reported emergence of fibers or materials from the skin accompanied by skin lesions and/or disturbing skin sensations. We collected detailed epidemiologic data, performed clinical evaluations and geospatial analyses and analyzed materials collected from participants' skin. Results We identified 115 case-patients. The prevalence was 3.65 (95% CI = 2.98, 4.40) cases per 100,000 enrollees. There was no clustering of cases within the 13-county KPNC catchment area (p = .113). Case-patients had a median age of 52 years (range: 17–93) and were primarily female (77%) and Caucasian (77%). Multi-system complaints were common; 70% reported chronic fatigue and 54% rated their overall health as fair or poor with mean Physical Component Scores and Mental Component Scores of 36.63 (SD = 12.9) and 35.45 (SD = 12.89), respectively. Cognitive deficits were detected in 59% of case-patients and 63% had evidence of clinically significant somatic complaints; 50% had drugs detected in hair samples and 78% reported exposure to solvents. Solar elastosis was the most common histopathologic abnormality (51% of biopsies); skin lesions were most consistent with arthropod bites or chronic excoriations. No parasites or mycobacteria were detected. Most materials collected from participants' skin were composed of cellulose, likely of cotton origin. Conclusions This unexplained dermopathy was rare among this population of Northern California residents, but associated with significantly reduced health-related quality of

  10. Congenital Aural Stenosis: Clinical Features and Long-term Outcomes.

    PubMed

    Li, Chen-Long; Chen, Ying; Chen, Yong-Zheng; Fu, Yao-Yao; Zhang, Tian-Yu

    2016-01-01

    The aim of the present study was to comprehensively evaluate the clinical features and long-term outcomes of congenital aural stenosis (CAS). This study presents a retrospective review of patients who underwent meatoplasty for CAS at a tertiary referral hospital from 2008 to 2015. A total of 246 meatoplasty procedures were performed on 232 patients in the present study. We performed multivariate regression analysis. Except in the age < 6 years group, no significant difference was observed among different age groups for cholesteatoma formation, p > 0.05. Except for the stenosis of the external auditory canal (EAC) (>4 mm) group, the other stenosis of EAC groups were not associated with cholesteatoma formation, p > 0.05. Postoperative air-bone gaps (ABG) less than 30 dB occurred in 77.3% (99/128) of the patients, and the Jahrsdoerfer score was associated with postoperative ABG, p < 0.001. The complication rate of CAS was 13.8% (20/144), and males showed a higher risk for postoperative complications (OR, 6.563; 95% CI, 1.268-33.966, p = 0.025). These results indicate that meatoplasty was an effective surgical intervention for CAS, showing a stable hearing outcome with prolonged follow-up. There was no significant difference between the cholesteatoma and no cholesteatoma groups for hearing outcomes, p > 0.05. PMID:27257165

  11. Etiological and Clinical Features of Childhood Psychotic Symptoms

    PubMed Central

    Polanczyk, Guilherme; Moffitt, Terrie E.; Arseneault, Louise; Cannon, Mary; Ambler, Antony; Keefe, Richard S. E.; Houts, Renate; Odgers, Candice L.; Caspi, Avshalom

    2013-01-01

    Context It has been reported that childhood psychotic symptoms are common in the general population and may signal neurodevelopmental processes that lead to schizophrenia. However, it is not clear whether these symptoms are associated with the same extensive risk factors established for adult schizophrenia. Objective To examine the construct validity of children’s self-reported psychotic symptoms by testing whether these symptoms share the risk factors and clinical features of adult schizophrenia. Design Prospective, longitudinal cohort study of a nationally representative birth cohort in Great Britain. Participants A total of 2232 twelve-year-old children followed up since age 5 years (retention, 96%). Main Outcome Measure Children’s self-reported hallucinations and delusions. Results Children’s psychotic symptoms are familial and heritable and are associated with social risk factors (eg, urbanicity); cognitive impairments at age 5; home-rearing risk factors (eg, maternal expressed emotion); behavioral, emotional, and educational problems at age 5; and comorbid conditions, including self-harm. Conclusions The results provide a comprehensive picture of the construct validity of children’s self-reported psychotic symptoms. For researchers, the findings indicate that children who have psychotic symptoms can be recruited for neuroscience research to determine the pathogenesis of schizophrenia. For clinicians, the findings indicate that psychotic symptoms in childhood are often a marker of an impaired developmental process and should be actively assessed. PMID:20368509

  12. Clinical and Immunological Features of Common Variable Immunodeficiency in China

    PubMed Central

    Lin, Lian-Jun; Wang, Yu-Chuan; Liu, Xin-Min

    2015-01-01

    Background: Common variable immunodeficiency (CVID) is one of the most common symptomatic primary immunodeficiency syndromes. The purpose of this article was to broaden our knowledge about CVID for better diagnosis and treatment. Methods: Clinical and immunological features of 40 Chinese patients with CVID were analyzed retrospectively. Results: The median age at onset was 11-year-old (range 4–51 years). The median age at diagnosis was 14.5-year-old (range 5–66 years). The average time of delay in diagnosis was 5.3 years (range 1–41 years). The most common main complaint was fever due to infections (35 cases, 87.5%). Pneumonia (28 cases, 70%) was the most common type of infections. Bronchiectasis was present in 6 patients (15%). Autoimmune disease was detected in 6 cases of CVID, and malignancy in 2 cases. The median total serum levels of IgG, IgA, and IgM at diagnosis were 1.07 g/L, 0.07 g/L, and 0.28 g/L, respectively. The percentages of CD3−/CD10+ B-cells were 1%–3.14%. Conclusions: Infection is the most frequent presentation of CVID. Patients with unexplainable infections should receive further examination including serum immunoglobulin (Ig) and lymphocyte subset analysis. Regular and sufficient substitution with Ig is recommended. PMID:25635425

  13. Clinical features of isolated dissections of abdominal aortic branches.

    PubMed

    Naganuma, Michio; Matsui, Hiroki; Fushimi, Kiyohide; Yasunaga, Hideo

    2016-06-01

    Isolated dissection of an abdominal aortic branch is a rare entity, and previous reports regarding the condition have been based only on small case-series studies. Using a national inpatient database in Japan, we describe the clinical features of patients with isolated celiac, superior mesenteric, splenic, and hepatic artery dissections (ICAD, ISMAD, ISAD, and IHAD). We extracted data on inpatients who were diagnosed with ICAD, ISMAD, ISAD, or IHAD from the Japanese diagnosis procedure combination database, including patients' age and sex, putative risk factors (smoking status and specific comorbidities), treatments (blood transfusion, transcatheter arterial embolization (TAE) and surgical procedures), and outcomes (in-hospital complications and death). Among 18.3 million inpatients in the database between July 2010 and March 2013, we identified 276 ICAD, 715 ISMAD, 23 ISAD and 11 IHAD. The percentage of males was 78-92 %, and the mean age was 54.7-56.8 years. Hypertension was seen in 48-65, and 35-65 % were smokers. Fourteen in-hospital deaths were identified in total. In the ICAD group, splenectomy was performed in one patient and TAE was performed in 26 patients. In the ISMAD group, 16 patients received surgical intervention. Most patients with isolated dissection of an abdominal aortic branch were treated conservatively, while a small percentage required TAE or open surgery. A small proportion of dissections resulted in death. PMID:25421008

  14. Clinical features of multiple epiphyseal dysplasia expressed in the knee.

    PubMed

    Miura, H; Noguchi, Y; Mitsuyasu, H; Nagamine, R; Urabe, K; Matsuda, S; Iwamoto, Y

    2000-11-01

    The purpose of this study is to clarify the clinical features of the knee affected by multiple epiphyseal dysplasia. Thirty-one cases of multiple epiphyseal dysplasia were reviewed. Of the patients, 11 were male and 20 were female. The average age at onset of symptoms was 22.5 years. The average age at initial visit to the authors' hospital was 28.9 years. Radiographic findings showed epiphyseal abnormality of the knee in all but two (93%) cases. Irregularity, segmentation of the epiphysis, widening of the joint space, and genu valgum deformity were the dominant findings before epiphyseal closure. After epiphyseal closure, the most characteristic finding was a shallow femoral trochlear groove, which was observed in 56.5% of the cases. Other findings in adult patients included early onset osteoarthritic change, genu valgum, depression of the lateral tibial plateau, and multiple free bodies. However, there still is a possibility that multiple epiphyseal dysplasia exists, even if the patient lacks a shallow femoral trochlear groove. If genu valgum or varum, free bodies, and premature osteoarthritis are observed, one should evaluate other joints, keeping a diagnosis of multiple epiphyseal dysplasia in mind. Patients with knees that have a femoral trochlear groove of normal or near normal shape do exist, and premature osteoarthritic changes may develop in such patients. PMID:11064990

  15. Mucocele and fibroma: treatment and clinical features for differential diagnosis.

    PubMed

    Valério, Rodrigo Alexandre; de Queiroz, Alexandra Mussolino; Romualdo, Priscila Coutinho; Brentegani, Luiz Guilherme; de Paula-Silva, Francisco Wanderley Garcia

    2013-01-01

    Mucocele is a benign lesion occurring in the buccal mucosa as a result of the rupture of a salivary gland duct and consequent outpouring of mucin into soft tissue. It is usually caused by a local trauma, although in many cases the etiology is uncertain. Mucocele is more commonly found in children and young adults, and the most frequent site is the lower inner portion of the lips. Fibroma, on the other hand, is a benign tumor of fibrous connective tissue that can be considered a reactionary connective tissue hyperplasia in response to trauma and irritation. They usually present hard consistency, are nodular and asymptomatic, with a similar color to the mucosa, sessile base, smooth surface, located in the buccal mucosa along the line of occlusion, tongue and lip mucosa. Conventional treatment for both lesions is conservative surgical excision. Recurrence rate is low for fibroma and high for oral mucoceles. This report presents a series of cases of mucocele and fibroma treated by surgical excision or enucleation and the respective follow-up routine in the dental clinic and discusses the features to be considered in order to distinguish these lesions from each other. PMID:24474300

  16. Delta hepatitis: molecular biology and clinical and epidemiological features.

    PubMed Central

    Polish, L B; Gallagher, M; Fields, H A; Hadler, S C

    1993-01-01

    Hepatitis delta virus, discovered in 1977, requires the help of hepatitis B virus to replicate in hepatocytes and is an important cause of acute, fulminant, and chronic liver disease in many regions of the world. Because of the helper function of hepatitis delta virus, infection with it occurs either as a coinfection with hepatitis B or as a superinfection of a carrier of hepatitis B surface antigen. Although the mechanisms of transmission are similar to those of hepatitis B virus, the patterns of transmission of delta virus vary widely around the world. In regions of the world in which hepatitis delta virus infection is not endemic, the disease is confined to groups at high risk of acquiring hepatitis B infection and high-risk hepatitis B carriers. Because of the propensity of this viral infection to cause fulminant as well as chronic liver disease, continued incursion of hepatitis delta virus into areas of the world where persistent hepatitis B infection is endemic will have serious implications. Prevention depends on the widespread use of hepatitis B vaccine. This review focuses on the molecular biology and the clinical and epidemiologic features of this important viral infection. PMID:8358704

  17. Congenital Aural Stenosis: Clinical Features and Long-term Outcomes

    PubMed Central

    Li, Chen-long; Chen, Ying; Chen, Yong-zheng; Fu, Yao-yao; Zhang, Tian-yu

    2016-01-01

    The aim of the present study was to comprehensively evaluate the clinical features and long-term outcomes of congenital aural stenosis (CAS). This study presents a retrospective review of patients who underwent meatoplasty for CAS at a tertiary referral hospital from 2008 to 2015. A total of 246 meatoplasty procedures were performed on 232 patients in the present study. We performed multivariate regression analysis. Except in the age < 6 years group, no significant difference was observed among different age groups for cholesteatoma formation, p > 0.05. Except for the stenosis of the external auditory canal (EAC) (>4 mm) group, the other stenosis of EAC groups were not associated with cholesteatoma formation, p > 0.05. Postoperative air-bone gaps (ABG) less than 30 dB occurred in 77.3% (99/128) of the patients, and the Jahrsdoerfer score was associated with postoperative ABG, p < 0.001. The complication rate of CAS was 13.8% (20/144), and males showed a higher risk for postoperative complications (OR, 6.563; 95% CI, 1.268–33.966, p = 0.025). These results indicate that meatoplasty was an effective surgical intervention for CAS, showing a stable hearing outcome with prolonged follow-up. There was no significant difference between the cholesteatoma and no cholesteatoma groups for hearing outcomes, p > 0.05. PMID:27257165

  18. Clinical features of Eosinophilic esophagitis in children and adults.

    PubMed

    Miehlke, Stephan

    2015-10-01

    Eosinophilic esophagitis (EoE) may affect humans at any age with a predominance for Caucasian males. The clinical manifestation of EoE varies depending on the patient's age. Infants and young children may primarily present with unspecific symptoms such as feeding problems, vomiting and abdominal pain. In adolescents and adults, dysphagia and food impactation become the predominant symptoms. EoE should also be considered in cases of refractory heartburn in both children and adults. Concomitant allergic diseases such as asthma, rhinitis and eczema, as well as peripheral eosinophilia and elevated total serum IgE values are common in pediatric and adult EoE patients. EoE seems to be primarily a food antigen-driven disease, whereas in adults, aeroallergen sensitization may dominate. Endoscopic features of EoE include mucosal edema, furrows, exudates, corrugated rings, strictures, and the so-called crepe paper sign. There appears to be a shift from an inflammatory-predominant phenotype in young childhood towards a more fibrotic phenotype in adolescents and adults. Long-term follow studies suggest that EoE is a chronic and potentially progressive disease causing recurring dysphagia in the majority of cases. The prevalence of strictures significantly increases with the duration of untreated disease, stressing the importance of early diagnosis and consequent treatment of EoE. PMID:26552773

  19. Epilepsy in hypothalamic hamartoma: clinical and EEG features.

    PubMed

    Harvey, A Simon; Freeman, Jeremy L

    2007-06-01

    Hypothalamic hamartoma (HH) is a congenital malformation of the hypothalamus that may be asymptomatic or manifest with precocious puberty or seizures. Gelastic seizures often begin early in life, even in the newborn period, being manifest by frequent attacks of inappropriate laughter resulting from seizure activity in the HH. The scalp electroencephalogram (EEG) is often normal in children with gelastic seizures, such that the diagnosis of epilepsy and the finding of a HH are often delayed. In a proportion of children with HH, there is an epileptic progression, in which complex partial seizures with frontal, temporal, and lateralized clinical features appear, usually with the appearance of focal slowing and epileptiform activity on the interictal EEG. Further progression may ensue with the appearance of tonic or atonic drop attacks, generalized tonic-clonic seizures, and epileptic spasms; rarely, infantile spasms may be the presenting seizure type. With the appearance of generalized seizures, the interictal EEG shows bilaterally synchronous and generalized epileptiform activity, often in abundance. The mechanism of this evolution is incompletely understood but neocortical seizure propagation and secondary epileptogenesis are believed to be important. Paralleling the development of the focal and generalized electroclinical manifestations in children with HH is usually slowing of development and the appearance of behavioral problems. Fortunately, many of these neurologic manifestations can be arrested, or reversed, with effective surgical treatment directed at the HH. PMID:17544948

  20. Clinical and molecular features and therapeutic perspectives of spinal muscular atrophy with respiratory distress type 1

    PubMed Central

    Vanoli, Fiammetta; Rinchetti, Paola; Porro, Francesca; Parente, Valeria; Corti, Stefania

    2015-01-01

    Spinal muscular atrophy with respiratory distress (SMARD1) is an autosomal recessive neuromuscular disease caused by mutations in the IGHMBP2 gene, encoding the immunoglobulin μ-binding protein 2, leading to motor neuron degeneration. It is a rare and fatal disease with an early onset in infancy in the majority of the cases. The main clinical features are muscular atrophy and diaphragmatic palsy, which requires prompt and permanent supportive ventilation. The human disease is recapitulated in the neuromuscular degeneration (nmd) mouse. No effective treatment is available yet, but novel therapeutical approaches tested on the nmd mouse, such as the use of neurotrophic factors and stem cell therapy, have shown positive effects. Gene therapy demonstrated effectiveness in SMA, being now at the stage of clinical trial in patients and therefore representing a possible treatment for SMARD1 as well. The significant advancement in understanding of both SMARD1 clinical spectrum and molecular mechanisms makes ground for a rapid translation of pre-clinical therapeutic strategies in humans. PMID:26095024

  1. Clinical features of Clostridium difficile infection and molecular characterization of the isolated strains in a cohort of Danish hospitalized patients.

    PubMed

    Søes, L M; Brock, I; Persson, S; Simonsen, J; Pribil Olsen, K E; Kemp, M

    2012-02-01

    The purpose of this study was to compare clinical features of Clostridium difficile infection (CDI) to toxin gene profiles of the strains isolated from Danish hospitalized patients. C. difficile isolates were characterized by PCR based molecular typing methods including toxin gene profiling and analysis of deletions and truncating mutations in the toxin regulating gene tcdC. Clinical features were obtained by questionnaire. Thirty percent of the CDI cases were classified as community-acquired. Infection by C. difficile with genes encoding both toxin A, toxin B and the binary toxin was significantly associated with hospital-acquired/healthcare-associated CDI compared to community-acquired CDI. Significantly higher leukocyte counts and more severe clinical manifestations were observed in patients infected by C. difficile containing genes also encoding the binary toxin together with toxin A and B compared to patients infected by C. difficile harbouring only toxin A and B. In conclusion, infection by C. difficile harbouring genes encoding both toxin A, toxin B and the binary toxin were associated with hospital acquisition, higher leukocyte counts and severe clinical disease. PMID:21744281

  2. Hemizygosity at the elastin locus and clinical features of Williams syndrome

    SciTech Connect

    Morimoto, Y; Kuwano, A.; Kuwajima, K.

    1994-09-01

    Williams syndrome is a recognizable syndrome characterized by distinctive facial appearance, gregarious personality, mental retardation, congenital heart defect, particularly supravalvular aortic stenosis (SVAS), and joint limitation. SVAS is an autosomal vascular disorder and the elastin gene was disrupted in patients with SVAS. Ewat et al. reported that hemizygosity at the elastin locus was detected in four familial and five sporadic cases of Williams syndrome. However, three patients did not have SVAS. We reconfirmed hemizygosity at the elastin locus in five patients with typical clinical features of Williams syndrome. Hemizygosity was detected in four cases with SVAS. However, one patient with distinctive facial appearance and typical Williams syndrome personality had two alleles of the elastin gene, but he did not have the congenital heart anomaly. Williams syndrome is thought to be a contiguous gene disorder. Thus, our data suggest that the elastin gene is responsible for the vascular defect in patients with Williams syndrome, and flanking genes are responsible for characteristic facial appearance and personality.

  3. Clinical, Pathological, and Molecular Features of Lung Adenocarcinomas with AXL Expression.

    PubMed

    Sato, Katsuaki; Suda, Kenichi; Shimizu, Shigeki; Sakai, Kazuko; Mizuuchi, Hiroshi; Tomizawa, Kenji; Takemoto, Toshiki; Nishio, Kazuto; Mitsudomi, Tetsuya

    2016-01-01

    The receptor tyrosine kinase AXL is a member of the Tyro3-Axl-Mer receptor tyrosine kinase subfamily. AXL affects several cellular functions, including growth and migration. AXL aberration is reportedly a marker for poor prognosis and treatment resistance in various cancers. In this study, we analyzed clinical, pathological, and molecular features of AXL expression in lung adenocarcinomas (LADs). We examined 161 LAD specimens from patients who underwent pulmonary resections. When AXL protein expression was quantified (0, 1+, 2+, 3+) according to immunohistochemical staining intensity, results were 0: 35%; 1+: 20%; 2+: 37%; and 3+: 7% for the 161 samples. AXL expression status did not correlate with clinical features, including smoking status and pathological stage. However, patients whose specimens showed strong AXL expression (3+) had markedly poorer prognoses than other groups (P = 0.0033). Strong AXL expression was also significantly associated with downregulation of E-cadherin (P = 0.025) and CD44 (P = 0.0010). In addition, 9 of 12 specimens with strong AXL expression had driver gene mutations (6 with EGFR, 2 with KRAS, 1 with ALK). In conclusion, we found that strong AXL expression in surgically resected LADs was a predictor of poor prognosis. LADs with strong AXL expression were characterized by mesenchymal status, higher expression of stem-cell-like markers, and frequent driver gene mutations. PMID:27100677

  4. Clinical, Pathological, and Molecular Features of Lung Adenocarcinomas with AXL Expression

    PubMed Central

    Suda, Kenichi; Shimizu, Shigeki; Sakai, Kazuko; Mizuuchi, Hiroshi; Tomizawa, Kenji; Takemoto, Toshiki; Nishio, Kazuto; Mitsudomi, Tetsuya

    2016-01-01

    The receptor tyrosine kinase AXL is a member of the Tyro3-Axl-Mer receptor tyrosine kinase subfamily. AXL affects several cellular functions, including growth and migration. AXL aberration is reportedly a marker for poor prognosis and treatment resistance in various cancers. In this study, we analyzed clinical, pathological, and molecular features of AXL expression in lung adenocarcinomas (LADs). We examined 161 LAD specimens from patients who underwent pulmonary resections. When AXL protein expression was quantified (0, 1+, 2+, 3+) according to immunohistochemical staining intensity, results were 0: 35%; 1+: 20%; 2+: 37%; and 3+: 7% for the 161 samples. AXL expression status did not correlate with clinical features, including smoking status and pathological stage. However, patients whose specimens showed strong AXL expression (3+) had markedly poorer prognoses than other groups (P = 0.0033). Strong AXL expression was also significantly associated with downregulation of E-cadherin (P = 0.025) and CD44 (P = 0.0010). In addition, 9 of 12 specimens with strong AXL expression had driver gene mutations (6 with EGFR, 2 with KRAS, 1 with ALK). In conclusion, we found that strong AXL expression in surgically resected LADs was a predictor of poor prognosis. LADs with strong AXL expression were characterized by mesenchymal status, higher expression of stem-cell-like markers, and frequent driver gene mutations. PMID:27100677

  5. The prognostic impact of clinical and molecular features in hairy cell leukaemia variant and splenic marginal zone lymphoma.

    PubMed

    Hockley, Sarah L; Else, Monica; Morilla, Alison; Wotherspoon, Andrew; Dearden, Claire; Catovsky, Daniel; Gonzalez, David; Matutes, Estella

    2012-08-01

    Hairy cell leukaemia variant (HCL-variant) and splenic marginal zone lymphoma (SMZL) are disorders with overlapping features. We investigated the prognostic impact in these disorders of clinical and molecular features including IGH VDJ rearrangements, IGHV gene usage and TP 53 mutations. Clinical and laboratory data were collected before therapy from 35 HCL-variant and 68 SMZL cases. End-points were the need for treatment and overall survival. 97% of HCL-variant and 77% of SMZL cases required treatment (P = 0·009). Survival at 5 years was significantly worse in HCL-variant [57% (95% confidence interval 38-73%)] compared with SMZL [84% (71-91%); Hazard Ratio 2·25 (1·20-4·25), P = 0·01]. In HCL-variant, adverse prognostic factors for survival were older age (P = 0·04), anaemia (P = 0·01) and TP 53 mutations (P = 0·02). In SMZL, splenomegaly, anaemia and IGHV genes with >98% homology to the germline predicted the need for treatment; older age, anaemia and IGHV unmutated genes (100% homology) predicted shorter survival. IGHV gene usage had no impact on clinical outcome in either disease. The combination of unfavourable factors allowed patients to be stratified into risk groups with significant differences in survival. Although HCL-variant and SMZL share some features, they have different outcomes, influenced by clinical and biological factors. PMID:22594855

  6. Fecal incontinence in men: Causes and clinical and manometric features

    PubMed Central

    Muñoz-Yagüe, Teresa; Solís-Muñoz, Pablo; Ciriza de los Ríos, Constanza; Muñoz-Garrido, Francisco; Vara, Jesús; Solís-Herruzo, José Antonio

    2014-01-01

    AIM: To determine the causes and characteristics of fecal incontinence in men and to compare these features with those presented by a group of women with the same problem. METHODS: We analyzed the medical history, clinical and manometric data from 119 men with fecal incontinence studied in our unit and compared these data with those obtained from 645 women studied for the same problem. Response to treatment was evaluated after 6 mo of follow-up. RESULTS: Fifteen percent of patients studied in our unit for fecal incontinence were male. Men took longer than women before asking for medical help. Ano-rectal surgery was the most common risk factor for men related to fecal incontinence. Chronic diarrhea was present in more than 40% of patients in both groups. Decreased resting and external anal sphincter pressures were more frequent in women. No significant differences existed between the sexes regarding rectal sensitivity and recto-anal inhibitory reflex. In 17.8% of men, all presenting soiling, manometric findings did not justify fecal incontinence. Response to treatment was good in both groups, as 80.4% of patients improved and fecal incontinence disappeared in 13.2% of them. CONCLUSION: In our series, it was common that men waited longer in seeking medical help for fecal incontinence. Ano-rectal surgery was the major cause of this problem. Chronic diarrhea was a predisposing factor in both sexes. Manometric differences between groups were limited to an increased frequency of hypotony of the external anal sphincter in women. Fecal incontinence was controllable in most patients. PMID:24976729

  7. Bilateral Vitreous Hemorrhage in Children: Clinical Features and Outcomes

    PubMed Central

    Sudhalkar, Aditya; Chhablani, Jay; Rani, Padmaja Kumari; Jalali, Subhadra; Balakrishnan, Divya; Tyagi, Mudit

    2015-01-01

    Purpose: To determine the etiology, clinical features and outcomes of bilateral vitreous hemorrhage (VH) in children. Methods: This retrospective chart review was performed on patients with bilateral VH under the age of 18 at a tertiary eye care center in India. Data included demographics, details of history and ocular examination, reports of investigations, surgeries or other interventions performed, and final anatomical and visual outcomes. Patients were divided into two groups i.e., traumatic and non-traumatic (spontaneous). Results: The traumatic group was comprised of 37 patients including 27 male and 10 female subjects with mean age of 13.47 ± 5.31 years, the most common complaint was decreased vision (96.45%) and the most prevalent etiology was firecracker injury in 16 (43.2%) patients. Mean baseline visual acuity (VA) was 2.34 ± 1.31 logMAR which was significantly improved to 1.08 ± 0.23 logMAR (P = 0.042). The mean number of surgeries was 2.72 ± 1.43 in the traumatic VH and mean follow up period was 23.14 ± 6.54 months. The spontaneous group included 48 subjects comprised of 27 male and 21 female cases with mean age of 14.48 ± 2.03 years. The most common cause was vasculitis in 21 (43.75%) subjects including four patients with tuberculosis. Mean baseline VA was 1.97 ± 1.13 logMAR which showed a significant improvement to 0.82 ± 0.24 logMAR (P = 0.012) after mean follow up of 34.2 ± 11.2 months. Eleven patients required at least one major surgery. Conclusion: Vasculitis was the most common cause of spontaneous bilateral VH; traumatic VH most prevalently occurred due to firecracker injury. Final VA was better in the spontaneous group. PMID:26425315

  8. Association of Genotyping of Bacillus cereus with Clinical Features of Post-Traumatic Endophthalmitis

    PubMed Central

    Hong, Meng; Wang, Qian; Tang, Zhide; Wang, Youpei; Gu, Yunfeng; Lou, Yongliang; Zheng, Meiqin

    2016-01-01

    Bacillus cereus is the second most frequent cause of post-traumatic bacterial endophthalmitis. Although genotyping of B. cereus associated with gastrointestinal infections has been reported, little is known about the B. cereus clinical isolates associated with post-traumatic endophthalmitis. This is largely due to the limited number of clinical strains available isolated from infected tissues of patients with post-traumatic endophthalmitis. In this study, we report successful isolation of twenty-four B. cereus strains from individual patients with different disease severity of post-traumatic endophthalmitis. Phylogenetic analysis showed that all strains could be categorized into three genotypes (GTI, GTII and GTIII) and the clinical score showed significant differences among these groups. We then further performed genotyping using the vrrA gene, and evaluated possible correlation of genotype with the clinical features of B. cereus–caused post-traumatic endophthalmitis, and with the prognosis of infection by conducting follow-up with patients for up to 2 months. We found that the disease of onset and final vision acuity were significantly different among the three groups. These results suggested that the vrrA gene may play a significant role in the pathogenesis of endophthalmitis, and genotyping of B. cereus has the potential for predicting clinical manifestation and prognosis of endophthalmitis. To the best of our knowledge, this is the first report of isolation of large numbers of clinical isolates of B. cereus from patients with endophthalmitis. This work sets the foundation for future investigation of the pathogenesis endophthalmitis caused by B. cereus infection. PMID:26886446

  9. Mitochondrial neurogastrointestinal encephalomyopathy in three siblings: clinical, genetic and neuroradiological features.

    PubMed

    Schüpbach, W M M; Vadday, K Madhavi; Schaller, A; Brekenfeld, C; Kappeler, L; Benoist, J F; Xuan-Huong, C Nguyen-Thi; Burgunder, J M; Seibold, F; Gallati, S; Mattle, H P

    2007-02-01

    Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a rare autosomal recessive disorder in which a nuclear mutation of the thymidine phosphorylase (TP) gene causes mitochondrial genomic dysfunction. Patients suffer from gastrointestinal dysmotility, cachexia, ptosis, external ophthalmoparesis, myopathy and polyneuropathy. Magnetic resonance imaging (MRI) shows leukoencephalopathy. We describe clinical, genetic and neuroradiological features of three brothers affected with MNGIE. Clinical examination, laboratory analyses, MRI and magnetic resonance spectroscopy (MRS) of the brain, and genetic analysis have been performed in all six members of the family with the three patients with MNGIE. Two of them are monozygous twins. They all suffered from gastrointestinal dysmotility, cachexia, ophthalmoplegia, muscular atrophies, and polyneuropathy. Urinary thymidine was elevated in the patients related to the severity of clinical disease, and urinary thymidine (normally not detectable) was also found in a heterozygous carrier. Brain MRI showed leukoencephalopathy in all patients; however, their cognitive functioning was normal. Brain MRS demonstrated reduced N-acetylaspartate and choline in severely affected areas. MRI of heterozygous carriers was normal. A new mutation (T92N) in the TP gene was identified. Urinary thymidine is for the first time reported to be detectable in a heterozygous carrier. MRS findings indicate loss of neurons, axons, and glial cells in patients with MNGIE, but not in heterozygous carriers. PMID:17294068

  10. The clinical and genetic features of the COPD asthma overlap syndrome

    PubMed Central

    Hardin, Megan; Cho, Michael; McDonald, Merry-Lynn; Beaty, Terri; Ramsdell, Joe; Bhatt, Surya; van Beek, Edwin J. R.; Make, Barry J.; Crapo, James D.; Silverman, Edwin K.; Hersh, Craig P.

    2014-01-01

    Background Individuals with COPD and asthma are an important but poorly characterized group. The genetic determinants of COPD-asthma overlap have not been studied. Objective Identify clinical features and genetic risk factors for COPD-asthma overlap. Methods Subjects were current or former smoking non-Hispanic whites (NHW) or African-Americans (AA) with COPD. Overlap subjects reported a history of physician-diagnosed asthma before the age of 40. We compared clinical and radiographic features between COPD and overlap subjects. We performed genome-wide association studies (GWAS) in the NHW and AA populations, and combined these results in a meta-analysis. Results More women and African Americans reported a history of asthma. Overlap subjects had more severe and more frequent respiratory exacerbations, less emphysema, and greater airway wall thickness compared to subjects with COPD alone. The NHW GWAS identified SNPs in CSMD1 (rs11779254, P=1.57×10−6) and SOX5(rs59569785, P=1.61×10−6) and the meta-analysis identified SNPs in the gene GPR65 (rs6574978, P=1.18×10−7) associated with COPD-asthma overlap. Conclusions Overlap subjects have more exacerbations, less emphysema and more airway disease for any degree of lung function impairment compared to COPD alone. We identified novel genetic variants associated with this syndrome. COPD-asthma overlap is an important syndrome and may require distinct clinical management. PMID:24876173

  11. The clinical and genetic features of COPD-asthma overlap syndrome.

    PubMed

    Hardin, Megan; Cho, Michael; McDonald, Merry-Lynn; Beaty, Terri; Ramsdell, Joe; Bhatt, Surya; van Beek, Edwin J R; Make, Barry J; Crapo, James D; Silverman, Edwin K; Hersh, Craig P

    2014-08-01

    Individuals with chronic obstructive pulmonary disease (COPD) and asthma are an important but poorly characterised group. The genetic determinants of COPD and asthma overlap have not been studied. The aim of this study was to identify clinical features and genetic risk factors for COPD and asthma overlap. Subjects were current or former smoking non-Hispanic whites or African-Americans with COPD. Overlap subjects reported a history of physician-diagnosed asthma before the age of 40 years. We compared clinical and radiographic features between COPD and overlap subjects. We performed genome-wide association studies (GWAS) in the non-Hispanic whites and African-American populations, and combined these results in a meta-analysis. More females and African-Americans reported a history of asthma. Overlap subjects had more severe and more frequent respiratory exacerbations, less emphysema and greater airway wall thickness compared to subjects with COPD alone. The non-Hispanic white GWAS identified single nucleotide polymorphisms in the genes CSMD1 (rs11779254, p=1.57 × 10(-6)) and SOX5 (rs59569785, p=1.61 × 10(-6)) and the meta-analysis identified single nucleotide polymorphisms in the gene GPR65 (rs6574978, p=1.18 × 10(-7)) associated with COPD and asthma overlap. Overlap subjects have more exacerbations, less emphysema and more airway disease for any degree of lung function impairment compared to COPD alone. We identified novel genetic variants associated with this syndrome. COPD and asthma overlap is an important syndrome and may require distinct clinical management. PMID:24876173

  12. Statistical methods for detecting differentially abundant features in clinical metagenomic samples.

    PubMed

    White, James Robert; Nagarajan, Niranjan; Pop, Mihai

    2009-04-01

    Numerous studies are currently underway to characterize the microbial communities inhabiting our world. These studies aim to dramatically expand our understanding of the microbial biosphere and, more importantly, hope to reveal the secrets of the complex symbiotic relationship between us and our commensal bacterial microflora. An important prerequisite for such discoveries are computational tools that are able to rapidly and accurately compare large datasets generated from complex bacterial communities to identify features that distinguish them.We present a statistical method for comparing clinical metagenomic samples from two treatment populations on the basis of count data (e.g. as obtained through sequencing) to detect differentially abundant features. Our method, Metastats, employs the false discovery rate to improve specificity in high-complexity environments, and separately handles sparsely-sampled features using Fisher's exact test. Under a variety of simulations, we show that Metastats performs well compared to previously used methods, and significantly outperforms other methods for features with sparse counts. We demonstrate the utility of our method on several datasets including a 16S rRNA survey of obese and lean human gut microbiomes, COG functional profiles of infant and mature gut microbiomes, and bacterial and viral metabolic subsystem data inferred from random sequencing of 85 metagenomes. The application of our method to the obesity dataset reveals differences between obese and lean subjects not reported in the original study. For the COG and subsystem datasets, we provide the first statistically rigorous assessment of the differences between these populations. The methods described in this paper are the first to address clinical metagenomic datasets comprising samples from multiple subjects. Our methods are robust across datasets of varied complexity and sampling level. While designed for metagenomic applications, our software can also be applied

  13. Newly Described Clinical and Immunopathological Feature of Dermatitis Herpetiformis

    PubMed Central

    Bonciolini, Veronica; Bonciani, Diletta; Verdelli, Alice; D'Errico, Antonietta; Antiga, Emiliano; Fabbri, Paolo; Caproni, Marzia

    2012-01-01

    Dermatitis herpetiformis (DH) is an inflammatory cutaneous disease with typical histopathological and immunopathological findings clinically characterized by intensely pruritic polymorphic lesions with a chronic-relapsing course. In addition to classic clinical manifestations of DH, atypical variants are more and more frequently reported and histological and immunological are added to them, whereas the impact on quality of life of patients with DH is increasingly important to a certain diagnosis. The aim of this paper is to describe all the possible clinical, histological, and immunological variants of DH in order to facilitate the diagnosis of a rare disease and, therefore, little known. PMID:22701503

  14. Cardio-Facio-Cutaneous Syndrome: Clinical Features, Diagnosis, and Management Guidelines

    PubMed Central

    Magoulas, Pilar L.; Adi, Saleh; Kavamura, Maria Ines; Neri, Giovanni; Noonan, Jacqueline; Pierpont, Elizabeth I.; Reinker, Kent; Roberts, Amy E.; Shankar, Suma; Sullivan, Joseph; Wolford, Melinda; Conger, Brenda; Santa Cruz, Molly; Rauen, Katherine A.

    2014-01-01

    Cardio-facio-cutaneous syndrome (CFC) is one of the RASopathies that bears many clinical features in common with the other syndromes in this group, most notably Noonan syndrome and Costello syndrome. CFC is genetically heterogeneous and caused by gene mutations in the Ras/mitogen-activated protein kinase pathway. The major features of CFC include characteristic craniofacial dysmorphology, congenital heart disease, dermatologic abnormalities, growth retardation, and intellectual disability. It is essential that this condition be differentiated from other RASopathies, as a correct diagnosis is important for appropriate medical management and determining recurrence risk. Children and adults with CFC require multidisciplinary care from specialists, and the need for comprehensive management has been apparent to families and health care professionals caring for affected individuals. To address this need, CFC International, a nonprofit family support organization that provides a forum for information, support, and facilitation of research in basic medical and social issues affecting individuals with CFC, organized a consensus conference. Experts in multiple medical specialties provided clinical management guidelines for pediatricians and other care providers. These guidelines will assist in an accurate diagnosis of individuals with CFC, provide best practice recommendations, and facilitate long-term medical care. PMID:25180280

  15. [Clinical features and DGUOK mutations of an infant with mitochondrial DNA depletion syndrome].

    PubMed

    Deng, Mei; Lin, Wei-Xia; Guo, Li; Zhang, Zhan-Hui; Song, Yuan-Zong

    2016-06-01

    The aim of this study was to investigate the clinical features and DGUOK gene mutations of an infant with mitochondrial DNA depletion syndrome (MDS). The patient (more than 7 months old) manifested as hepatosplenomegaly, abnormal liver function, nystagmus and psychomotor retardation. Genetic DNA was extracted from peripheral blood samples of the patient and her parents. Targeted Exome Sequencing was performed to explore the genetic causes. Sanger sequencing was carried out to confirm the detected mutations. The sequencing results showed that the patient was a compound heterozygote for c.679G>A and c.817delT in the DGUOK gene. The former was a reportedly pathogenic missense mutation of maternal origin, while the latter, a frameshift mutation from the father, has not been described yet. The findings in this study expand the mutation spectrum of DGUOK gene, and provide molecular evidence for the etiologic diagnosis of the patient as well as for the genetic counseling and prenatal diagnosis in the family. PMID:27324545

  16. A new case of malonyl-CoA decarboxylase deficiency with mild clinical features.

    PubMed

    Liu, Huan; Tan, Dongqiong; Han, Lianshu; Ye, Jun; Qiu, Wenjuan; Gu, Xuefan; Zhang, Huiwen

    2016-05-01

    Malonyl-CoA decarboxylase deficiency is an extremely rare autosomal recessive inborn error of fatty acid metabolism. It usually follows a severe disease course and presents poor prognosis without treatment. Here, we report an affected female juvenile with a mild clinical and biochemical phenotype who mainly featured poor schooling without cardiomyopathy and metabolic acidosis. She was suspected of malonyl-CoA decarboxylase deficiency due to a 57-kb deletion in 16q23.3 encompassing the MLCYD gene revealed by chromosome microarray. Malonyl-CoA decarboxylase deficiency was then confirmed by acylcarnitine analysis and organic acid analysis. Real-time PCR analysis of the patient revealed the first three exon deletion of the MLYCD gene, which was maternally inherited. DNA sequencing of the MLYCD gene of the patient identified a novel heterozygous mutation (c.911G>A, p.G304E) in exon 4 that was paternally inherited. The patient urine malonic acid dissolved and had a better school record in 6 month after initiation of fat-limited diet. At 1 year post treatment, the blood malonylcarnitine level decreased remarkably. Our result expands the phenotype of malonyl-CoA decarboxylase deficiency and suggests attentions should be paid to the mild form of disorders, for example, malonyl-CoA decarboxylase deficiency, which usually present a severe disease course. © 2016 Wiley Periodicals, Inc. PMID:26858006

  17. Correlation between CAG repeat length and clinical features in Machado-Joseph disease

    SciTech Connect

    Maciel, P.; Gaspar, C.; Silveira, I.

    1995-07-01

    Machado-Joseph disease (MJD) is associated with the expansion of a CAG trinucleotide repeat in a novel gene on 14q32.1. We confirmed the presence of this expansion in 156 MJD patients from 33 families of different geographic origins: 15 Portuguese Azorean, 2 Brazilian, and 16 North American of Portuguese Azorean descent. Normal chromosomes contain between 12 and 37 CAG repeats in the MJD gene, whereas MJD gene carriers have alleles within the expanded range of 62-84 CAG units. The distribution of expanded alleles and the gap between normal and expanded allele sizes is either inconsistent with a premutation hypothesis or most (if not all) of the alleles we studied descend from a common ancestor. There is a strong correlation between the expanded repeat size and the age at onset of the disease as well as the clinical presentation. There is mild instability of the CAG tract length with transmission of the expanded alleles; both increase and decrease in size between parents and progeny occur, with larger variations in male than in female transmissions. Together, these effects can partly explain the variability of age at onset and of phenotypic features in MJD; however, other modifying factors must exist. 37 refs., 6 figs.

  18. Correlation between CAG Repeat Length and Clinical Features in Machado-Joseph Disease

    PubMed Central

    Maciel, Patrícia; Gaspar, Claudia; DeStefano, Anita L.; Silveira, Isabel; Coutinho, Paula; Radvany, João; Dawson, David M.; Sudarsky, Lewis; Guimarães, João; Loureiro, Jose E. L.; Nezarati, Marjan M.; Corwin, Lee I.; Lopes-Cendes, Iscia; Rooke, Karen; Rosenberg, Roger; MacLeod, Patrick; Farrer, Lindsay A.; Sequeiros, Jorge; Rouleau, Guy A.

    1995-01-01

    Machado-Joseph disease (MJD) is associated with the expansion of a CAG trinucleotide repeat in a novel gene on 14q32.1. We confirmed the presence of this expansion in 156 MJD patients from 33 families of different geographic origins: 15 Portuguese Azorean, 2 Brazilian, and 16 North American of Portuguese Azorean descent. Normal chromosomes contain between 12 and 37 CAG repeats in the MJD gene, whereas MJD gene carriers have alleles within the expanded range of 62–84 CAG units. The distribution of expanded alleles and the gap between normal and expanded allele sizes is either inconsistent with a premutation hypothesis or most (if not all) of the alleles we studied descend from a common ancestor. There is a strong correlation between the expanded repeat size and the age at onset of the disease as well as the clinical presentation. There is mild instability of the CAG tract length with transmission of the expanded alleles; both increase and decrease in size between parents and progeny occur, with larger variations in male than in female transmissions. Together, these effects can partly explain the variability of age at onset and of phenotypic features in MJD; however, other modifying factors must exist. ImagesFigure 3 PMID:7611296

  19. Molecular biology of testicular germ cell tumors: unique features awaiting clinical application.

    PubMed

    Boublikova, Ludmila; Buchler, Tomas; Stary, Jan; Abrahamova, Jitka; Trka, Jan

    2014-03-01

    Testicular germ cell tumors (TGCTs) are the most common solid tumors in young adult men characterized by distinct biologic features and clinical behavior. Both genetic predispositions and environmental factors probably play a substantial role in their etiology. TGTCs arise from a malignant transformation of primordial germ cells in a process that starts prenatally, is often associated with a certain degree of gonadal dysgenesis, and involves the acquirement of several specific aberrations, including activation of SCF-CKIT, amplification of 12p with up-regulation of stem cell genes, and subsequent genetic and epigenetic alterations. Their embryonic and germ origin determines the unique sensitivity of TGCTs to platinum-based chemotherapy. Contrary to the vast majority of other malignancies, no molecular prognostic/predictive factors nor targeted therapy is available for patients with these tumors. This review summarizes the principal molecular characteristics of TGCTs that could represent a potential basis for development of novel diagnostic and treatment approaches. PMID:24182421

  20. Systematic genomic identification of colorectal cancer genes delineating advanced from early clinical stage and metastasis

    PubMed Central

    2013-01-01

    Background Colorectal cancer is the third leading cause of cancer deaths in the United States. The initial assessment of colorectal cancer involves clinical staging that takes into account the extent of primary tumor invasion, determining the number of lymph nodes with metastatic cancer and the identification of metastatic sites in other organs. Advanced clinical stage indicates metastatic cancer, either in regional lymph nodes or in distant organs. While the genomic and genetic basis of colorectal cancer has been elucidated to some degree, less is known about the identity of specific cancer genes that are associated with advanced clinical stage and metastasis. Methods We compiled multiple genomic data types (mutations, copy number alterations, gene expression and methylation status) as well as clinical meta-data from The Cancer Genome Atlas (TCGA). We used an elastic-net regularized regression method on the combined genomic data to identify genetic aberrations and their associated cancer genes that are indicators of clinical stage. We ranked candidate genes by their regression coefficient and level of support from multiple assay modalities. Results A fit of the elastic-net regularized regression to 197 samples and integrated analysis of four genomic platforms identified the set of top gene predictors of advanced clinical stage, including: WRN, SYK, DDX5 and ADRA2C. These genetic features were identified robustly in bootstrap resampling analysis. Conclusions We conducted an analysis integrating multiple genomic features including mutations, copy number alterations, gene expression and methylation. This integrated approach in which one considers all of these genomic features performs better than any individual genomic assay. We identified multiple genes that robustly delineate advanced clinical stage, suggesting their possible role in colorectal cancer metastatic progression. PMID:24308539

  1. Pine nut allergy: clinical features and major allergens characterization

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Pine nuts, the seeds of pine trees, are widely used for human consumption in Europe, America, and Asia. The aims of this study were to evaluate IgE-mediated hypersensitivity to pine nut in a large number of patients with details of clinical reactions, and to characterize major pine nut allergens. Th...

  2. "Wild type" GIST: Clinicopathological features and clinical practice.

    PubMed

    Wada, Ryuichi; Arai, Hiroki; Kure, Shoko; Peng, Wei-Xia; Naito, Zenya

    2016-08-01

    Gastrointestinal stromal tumor (GIST) is a mesenchymal tumor of the gastrointestinal tract. Mutation of KIT and PDGFRA genes is implicated in the tumorigenesis. Approximately 10% of GISTs do not harbor mutation of these genes, and they are designated as "wild type" GIST. They are classified into succinate dehydrogenase (SDH)-deficient and non-SDH-deficient groups. SDH-deficient group includes Carney triad and Carney Stratakis syndrome. The patients are young women. Tumors occur in the antrum of the stomach, and tumor cells are epithelioid. Lymph node metastasis is frequent. The non-SDH-deficient group includes neurofibromatosis (NF) type 1 and GISTs with mutations of BRAF, KRAS, and PIK3CA and with the ETV6-NTRK3 fusion gene. GIST in NF occurs in the small intestine, and tumor cells are spindle shaped. GIST with BRAF mutation arises in the small intestine. Attention to the age, gender, family history and other neoplasms may raise the prediction of syndromic disease. Location of the tumor, morphology, and pleomorphism of the tumor cells are further informative. Lymphovascular invasion should be carefully evaluated. The determination of KIT expression is essential for the diagnosis. When wild type GIST is suspected, intensive genetic analysis is required. Further, a careful and long-time observation is recommended. PMID:27427238

  3. Extracting BI-RADS Features from Portuguese Clinical Texts

    PubMed Central

    Nassif, Houssam; Cunha, Filipe; Moreira, Inês C.; Cruz-Correia, Ricardo; Sousa, Eliana; Page, David; Burnside, Elizabeth; Dutra, Inês

    2013-01-01

    In this work we build the first BI-RADS parser for Portuguese free texts, modeled after existing approaches to extract BI-RADS features from English medical records. Our concept finder uses a semantic grammar based on the BIRADS lexicon and on iterative transferred expert knowledge. We compare the performance of our algorithm to manual annotation by a specialist in mammography. Our results show that our parser’s performance is comparable to the manual method. PMID:23797461

  4. Clinical features and multidisciplinary approaches to dementia care

    PubMed Central

    Grand, Jacob HG; Caspar, Sienna; MacDonald, Stuart WS

    2011-01-01

    Dementia is a clinical syndrome of widespread progressive deterioration of cognitive abilities and normal daily functioning. These cognitive and behavioral impairments pose considerable challenges to individuals with dementia, along with their family members and caregivers. Four primary dementia classifications have been defined according to clinical and research criteria: 1) Alzheimer’s disease; 2) vascular dementias; 3) frontotemporal dementias; and 4) dementia with Lewy bodies/Parkinson’s disease dementia. The cumulative efforts of multidisciplinary healthcare teams have advanced our understanding of dementia beyond basic descriptions, towards a more complete elucidation of risk factors, clinical symptoms, and neuropathological correlates. The characterization of disease subtypes has facilitated targeted management strategies, advanced treatments, and symptomatic care for individuals affected by dementia. This review briefly summarizes the current state of knowledge and directions of dementia research and clinical practice. We provide a description of the risk factors, clinical presentation, and differential diagnosis of dementia. A summary of multidisciplinary team approaches to dementia care is outlined, including management strategies for the treatment of cognitive impairments, functional deficits, and behavioral and psychological symptoms of dementia. The needs of individuals with dementia are extensive, often requiring care beyond traditional bounds of medical practice, including pharmacologic and non-pharmacologic management interventions. Finally, advanced research on the early prodromal phase of dementia is reviewed, with a focus on change-point models, trajectories of cognitive change, and threshold models of pathological burden. Future research goals are outlined, with a call to action for social policy initiatives that promote preventive lifestyle behaviors, and healthcare programs that will support the growing number of individuals affected by

  5. Genes and Pathways Involved in Adult Onset Disorders Featuring Muscle Mitochondrial DNA Instability

    PubMed Central

    Ahmed, Naghia; Ronchi, Dario; Comi, Giacomo Pietro

    2015-01-01

    Replication and maintenance of mtDNA entirely relies on a set of proteins encoded by the nuclear genome, which include members of the core replicative machinery, proteins involved in the homeostasis of mitochondrial dNTPs pools or deputed to the control of mitochondrial dynamics and morphology. Mutations in their coding genes have been observed in familial and sporadic forms of pediatric and adult-onset clinical phenotypes featuring mtDNA instability. The list of defects involved in these disorders has recently expanded, including mutations in the exo-/endo-nuclease flap-processing proteins MGME1 and DNA2, supporting the notion that an enzymatic DNA repair system actively takes place in mitochondria. The results obtained in the last few years acknowledge the contribution of next-generation sequencing methods in the identification of new disease loci in small groups of patients and even single probands. Although heterogeneous, these genes can be conveniently classified according to the pathway to which they belong. The definition of the molecular and biochemical features of these pathways might be helpful for fundamental knowledge of these disorders, to accelerate genetic diagnosis of patients and the development of rational therapies. In this review, we discuss the molecular findings disclosed in adult patients with muscle pathology hallmarked by mtDNA instability. PMID:26251896

  6. Resolution of Elevated Urine Glycosaminoglycans and Clinical Features of Mucopolysaccharidosis After Successful Treatment of Neuroblastoma.

    PubMed

    Hilgers, Megan V; Whitley, Chester B; Moertel, Christopher L

    2016-08-01

    We report a patient with stage 3 ganglioneuroblastoma who initially presented with clinical and laboratory features consistent with mucopolysaccharidosis including coarse facial features, developmental delay, and an elevated quantitative urine glycosaminoglycan (GAG) level. All mucopolysaccharidosis features resolved following successful treatment of neuroblastoma. High GAG levels have been documented in the pediatric oncology literature, yet not as a potential marker of malignancy or other target for clinical utility. This patient prompts further investigation into the relationship between neuroblastoma and elevated GAG levels. PMID:27203570

  7. Gluteal Tendinopathy: Integrating Pathomechanics and Clinical Features in Its Management.

    PubMed

    Grimaldi, Alison; Fearon, Angela

    2015-11-01

    Synopsis Gluteal tendinopathy is now believed to be the primary local source of lateral hip pain, or greater trochanteric pain syndrome, previously referred to as trochanteric bursitis. This condition is prevalent, particularly among postmenopausal women, and has a considerable negative influence on quality of life. Improved prognosis and outcomes in the future for those with gluteal tendinopathy will be underpinned by advances in diagnostic testing, a clearer understanding of risk factors and comorbidities, and evidence-based management programs. High-quality studies that meet these requirements are still lacking. This clinical commentary provides direction to assist the clinician with assessment and management of the patient with gluteal tendinopathy, based on currently limited available evidence on this condition and the wider tendon literature and on the combined clinical experience of the authors. J Orthop Sports Phys Ther 2015;45(11):910-922. Epub 17 Sep 2015. doi:10.2519/jospt.2015.5829. PMID:26381486

  8. LEPROSY NEPHROPATHY: A REVIEW OF CLINICAL AND HISTOPATHOLOGICAL FEATURES

    PubMed Central

    da Silva, Geraldo Bezerra; Daher, Elizabeth De Francesco; Pires, Roberto da Justa; Pereira, Eanes Delgado Barros; Meneses, Gdayllon Cavalcante; Araújo, Sônia Maria Holanda Almeida; Barros, Elvino José Guardão

    2015-01-01

    Leprosy is a chronic disease caused by Mycobacterium leprae, highly incapacitating, and with systemic involvement in some cases. Renal involvement has been reported in all forms of the disease, and it is more frequent in multibacillary forms. The clinical presentation is variable and is determined by the host immunologic system reaction to the bacilli. During the course of the disease there are the so called reactional states, in which the immune system reacts against the bacilli, exacerbating the clinical manifestations. Different renal lesions have been described in leprosy, including acute and chronic glomerulonephritis, interstitial nephritis, secondary amyloidosis and pyelonephritis. The exact mechanism that leads to glomerulonephritis in leprosy is not completely understood. Leprosy treatment includes rifampicin, dapsone and clofazimine. Prednisone and non-steroidal anti-inflammatory drugs may be used to control acute immunological episodes. PMID:25651321

  9. The Clinical Features of Sarcoidosis: A Comprehensive Review.

    PubMed

    Judson, Marc A

    2015-08-01

    Sarcoidosis has innumerable clinical manifestations, as the disease may affect every body organ. Furthermore, the severity of sarcoidosis involvement may range from an asymptomatic state to a life-threatening condition. This manuscript reviews a wide variety of common and less common clinical characteristics of sarcoidosis. These manifestations are presented organ by organ, although additional sections describe systemic and multiorgan presentations of sarcoidosis. The lung is the organ most commonly involved with sarcoidosis with at least 90 % of sarcoidosis patients demonstrating lung involvement in most series. The skin, eye, liver, and peripheral lymph node are the next most commonly clinically involved organs in most series, with the frequency of involvement ranging from 10 to 30 %. The actual frequency of sarcoidosis organ involvement is probably much higher as it is frequently asymptomatic and may avoid detection. This is particularly common with lung, liver, cardiac, and bone involvement. Cardiac sarcoidosis is present in 25 % of all sarcoidosis but only causes clinical problems in 5 % of them. Nevertheless, unlike sarcoidosis involvement of most other organs, it may be suddenly fatal. Therefore, it is important to screen for cardiac sarcoidosis in all sarcoidosis patients. All sarcoidosis patients should also be screened for eye involvement as asymptomatic patients may have eye involvement that may cause permanent vision impairment. Pulmonary fibrosis from sarcoidosis is usually slowly progressive but may be life-threatening because of the development of respiratory failure, pulmonary hypertension, or hemoptysis related to a mycetoma or bronchiectasis. Some manifestations of sarcoidosis are not organ-specific and probably are the result of a release of mediators from the sarcoid granuloma. Two such manifestations include small fiber neuropathy and fatigue syndromes, and they are observed in a large percentage of patients. PMID:25274450

  10. Pathogenesis, clinical features and management of hidradenitis suppurativa.

    PubMed Central

    Parks, R. W.; Parks, T. G.

    1997-01-01

    Hidradenitis suppurativa is a chronic skin condition involving the apocrine glandular zones. Affected patients may present with acute abscesses, but the condition often progresses to a chronic state with persistent pain, sepsis, sinus tract and fistula formation, purulent discharge and dermal scarring. Treatment of patients with severe disease can be difficult and may require complex surgical intervention. This review encompasses the pathogenesis, clinical manifestations and management options for patients with hidradenitis suppurativa. Images Figure 2 PMID:9135232

  11. Mendelian susceptibility to mycobacterial disease: genetic, immunological, and clinical features of inborn errors of IFN-γ immunity.

    PubMed

    Bustamante, Jacinta; Boisson-Dupuis, Stéphanie; Abel, Laurent; Casanova, Jean-Laurent

    2014-12-01

    Mendelian susceptibility to mycobacterial disease (MSMD) is a rare condition characterized by predisposition to clinical disease caused by weakly virulent mycobacteria, such as BCG vaccines and environmental mycobacteria, in otherwise healthy individuals with no overt abnormalities in routine hematological and immunological tests. MSMD designation does not recapitulate all the clinical features, as patients are also prone to salmonellosis, candidiasis and tuberculosis, and more rarely to infections with other intramacrophagic bacteria, fungi, or parasites, and even, perhaps, a few viruses. Since 1996, nine MSMD-causing genes, including seven autosomal (IFNGR1, IFNGR2, STAT1, IL12B, IL12RB1, ISG15, and IRF8) and two X-linked (NEMO, and CYBB) genes have been discovered. The high level of allelic heterogeneity has already led to the definition of 18 different disorders. The nine gene products are physiologically related, as all are involved in IFN-γ-dependent immunity. These disorders impair the production of (IL12B, IL12RB1, IRF8, ISG15, NEMO) or the response to (IFNGR1, IFNGR2, STAT1, IRF8, CYBB) IFN-γ. These defects account for only about half the known MSMD cases. Patients with MSMD-causing genetic defects may display other infectious diseases, or even remain asymptomatic. Most of these inborn errors do not show complete clinical penetrance for the case-definition phenotype of MSMD. We review here the genetic, immunological, and clinical features of patients with inborn errors of IFN-γ-dependent immunity. PMID:25453225

  12. Mendelian susceptibility to mycobacterial disease: genetic, immunological, and clinical features of inborn errors of IFN-γ immunity

    PubMed Central

    Bustamante, Jacinta; Boisson-Dupuis, Stéphanie; Abel, Laurent; Casanova, Jean-Laurent

    2014-01-01

    Mendelian susceptibility to mycobacterial disease (MSMD) is a rare condition characterized by predisposition to clinical disease caused by weakly virulent mycobacteria, such as BCG vaccines and environmental mycobacteria, in otherwise healthy individuals with no overt abnormalities in routine hematological and immunological tests. MSMD designation does not recapitulate all the clinical features, as patients are also prone to salmonellosis, candidiasis and tuberculosis, and more rarely to infections with other intramacrophagic bacteria, fungi, or parasites, and even, perhaps, a few viruses. Since 1996, nine MSMD-causing genes, including seven autosomal (IFNGR1, IFNGR2, STAT1, IL12B, IL12RB1, ISG15, and IRF8) and two X-linked (NEMO, CYBB) genes have been discovered. The high level of allelic heterogeneity has already led to the definition of 18 different disorders. The nine gene products are physiologically related, as all are involved in IFN-γ-dependent immunity. These disorders impair the production of (IL12B, IL12RB1, IRF8, ISG15, NEMO) or the response to (IFNGR1, IFNGR2, STAT1, IRF8, CYBB) IFN-γ. These defects account for only about half the known MSMD cases. Patients with MSMD-causing genetic defects may display other infectious diseases, or even remain asymptomatic. Most of these inborn errors do not show complete clinical penetrance for the case-definition phenotype of MSMD. We review here the genetic, immunological, and clinical features of patients with inborn errors of IFN-γ-dependent immunity. PMID:25453225

  13. Clinical Risk Prediction by Exploring High-Order Feature Correlations

    PubMed Central

    Wang, Fei; Zhang, Ping; Wang, Xiang; Hu, Jianying

    2014-01-01

    Clinical risk prediction is one important problem in medical informatics, and logistic regression is one of the most widely used approaches for clinical risk prediction. In many cases, the number of potential risk factors is fairly large and the actual set of factors that contribute to the risk is small. Therefore sparse logistic regression is proposed, which can not only predict the clinical risk but also identify the set of relevant risk factors. The inputs of logistic regression and sparse logistic regression are required to be in vector form. This limits the applicability of these models in the problems when the data cannot be naturally represented vectors (e.g., medical images are two-dimensional matrices). To handle the cases when the data are in the form of multi-dimensional arrays, we propose HOSLR: High-Order Sparse Logistic Regression, which can be viewed as a high order extension of sparse logistic regression. Instead of solving one classification vector as in conventional logistic regression, we solve for K classification vectors in HOSLR (K is the number of modes in the data). A block proximal descent approach is proposed to solve the problem and its convergence is guaranteed. Finally we validate the effectiveness of HOSLR on predicting the onset risk of patients with Alzheimer’s disease and heart failure. PMID:25954428

  14. Clinical and pathological features of alcohol-related brain damage.

    PubMed

    Zahr, Natalie M; Kaufman, Kimberley L; Harper, Clive G

    2011-05-01

    One of the sequelae of chronic alcohol abuse is malnutrition. Importantly, a deficiency in thiamine (vitamin B(1)) can result in the acute, potentially reversible neurological disorder Wernicke encephalopathy (WE). When WE is recognized, thiamine treatment can elicit a rapid clinical recovery. If WE is left untreated, however, patients can develop Korsakoff syndrome (KS), a severe neurological disorder characterized by anterograde amnesia. Alcohol-related brain damage (ARBD) describes the effects of chronic alcohol consumption on human brain structure and function in the absence of more discrete and well-characterized neurological concomitants of alcoholism such as WE and KS. Through knowledge of both the well-described changes in brain structure and function that are evident in alcohol-related disorders such as WE and KS and the clinical outcomes associated with these changes, researchers have begun to gain a better understanding of ARBD. This Review examines ARBD from the perspective of WE and KS, exploring the clinical presentations, postmortem brain pathology, in vivo MRI findings and potential molecular mechanisms associated with these conditions. An awareness of the consequences of chronic alcohol consumption on human behavior and brain structure can enable clinicians to improve detection and treatment of ARBD. PMID:21487421

  15. Suicide attempts and clinical features of bipolar patients

    PubMed Central

    Berkol, Tonguç D.; İslam, Serkan; Kırlı, Ebru; Pınarbaşı, Rasim; Özyıldırım, İlker

    2016-01-01

    Objectives: To identify clinical predictors of suicide attempts in patients with bipolar disorder. Methods: This study included bipolar patients who were treated in the Psychiatry Department, Haseki Training and Research Hospital, Istanbul, Turkey, between 2013 and 2014; an informed consent was obtained from the participants. Two hundred and eighteen bipolar patients were assessed by using the structured clinical interview for Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) Axis-I (SCID-I) in order to detect all possible psychiatric comorbid diagnoses. Clinical predictors of suicide attempts were examined in attempters and non-attempters. The study design was retrospective. Results: The lifetime suicide attempt rate for the entire sample was 19.2%. Suicide attempters with bipolar disorder had more lifetime comorbidity of eating disorder. Female gender and family history of mood disorder were significant predictors for suicide attempts. There was no difference between groups in terms of bipolar disorder subtype, onset age of bipolar disorder, total number of episodes, first and predominant episode type, suicide history in first degree relatives, severity of episodes, and hospitalization and being psychotic. Conclusion: Our study revealed that female gender, family history of mood disorder, and eating disorder are more frequent in bipolar patients with at least one suicide attempt. PMID:27279513

  16. Clinical features, comorbidity, and cognitive impairment in elderly bipolar patients

    PubMed Central

    Rise, Ida Vikan; Haro, Josep Maria; Gjervan, Bjørn

    2016-01-01

    Introduction Data specific to late-life bipolar disorder (BD) are limited. Current research is sparse and present guidelines are not adapted to this group of patients. Objectives We present a literature review on clinical characteristics, comorbidities, and cognitive impairment in patients with late-life BD. This review discusses common comorbidities that affect BD elders and how aging might affect cognition and treatment. Methods Eligible studies were identified in MedLine by the Medical Subject Headings terms “bipolar disorder” and “aged”. We only included original research reports published in English between 2012 and 2015. Results From 414 articles extracted, 16 studies were included in the review. Cardiovascular and respiratory conditions, type II diabetes, and endocrinological abnormalities were observed as highly prevalent. BD is associated with a high suicide risk. Bipolar elderly had an increased risk of dementia and performed worse on cognitive screening tests compared to age-matched controls across different levels of cognition. Despite high rates of medical comorbidity among bipolar elderly, a systematic under-recognition and undertreatment of cardiovascular disease have been suggested. Conclusion There was a high burden of physical comorbidities and cognitive impairment in late-life BD. Bipolar elderly might be under-recorded and undertreated in primary medical care, indicating that this group needs an adapted clinical assessment and specific clinical guidelines need to be established. PMID:27274256

  17. Viral etiology, clinical and laboratory features of adult hemophagocytic lymphohistiocytosis.

    PubMed

    Chen, Jinghong; Wang, Xuehua; He, Ping; Li, Yazhen; Si, Mengya; Fan, Zhichen; Chang, Xiaolan; Xie, Qindong; Jiao, Xiaoyang

    2016-03-01

    Secondary hemophagocytic lymphohistiocytosis (SHLH) is a potentially fatal hyperinflammatory syndrome with a heterogeneous etiology and has nonspecific clinical and laboratory findings. The diagnosis and treatment of adult SHLH is challenging because the etiology of the disease is difficult to identify, and the majority of reported cases are pediatric patients. The aim of this study was to describe the etiology, clinical characteristics, and outcomes of adult SHLH. Fifty-four adult patients who fulfilled the criteria of SHLH were enrolled in the study. Viral etiology, blood biomarkers, and clinical manifestations of SHLH were analyzed in these patients. Twenty-four SHLH patients had viraemia, whereas 30 SHLH patients were secondary to other diseases. Epstein-Barr virus (EBV) was the most common virus that associated SHLH among all viruses studied. Severe SHLH patients with EBV-viraemia presented significantly high levels of ferritin, lactate dehydrogenase, aspartate transaminase (AST), and alanine transaminase (ALT). Positively relationships existed between EBV DNA titers and levels of AST and ALT (P < 0.05). The prognosis of SHLH patients with EBV viraemia was worse than that of non-EBV SHLH and non-viral SHLH. Our data reveal that EBV is the major pathogen in virus-associated SHLH, and EBV load influence disease development in SHLH patients with EBV infection that prognosis is worse than other viruses associated SHLH. PMID:26287378

  18. HypertenGene: extracting key hypertension genes from biomedical literature with position and automatically-generated template features

    PubMed Central

    2009-01-01

    Background The genetic factors leading to hypertension have been extensively studied, and large numbers of research papers have been published on the subject. One of hypertension researchers' primary research tasks is to locate key hypertension-related genes in abstracts. However, gathering such information with existing tools is not easy: (1) Searching for articles often returns far too many hits to browse through. (2) The search results do not highlight the hypertension-related genes discovered in the abstract. (3) Even though some text mining services mark up gene names in the abstract, the key genes investigated in a paper are still not distinguished from other genes. To facilitate the information gathering process for hypertension researchers, one solution would be to extract the key hypertension-related genes in each abstract. Three major tasks are involved in the construction of this system: (1) gene and hypertension named entity recognition, (2) section categorization, and (3) gene-hypertension relation extraction. Results We first compare the retrieval performance achieved by individually adding template features and position features to the baseline system. Then, the combination of both is examined. We found that using position features can almost double the original AUC score (0.8140vs.0.4936) of the baseline system. However, adding template features only results in marginal improvement (0.0197). Including both improves AUC to 0.8184, indicating that these two sets of features are complementary, and do not have overlapping effects. We then examine the performance in a different domain--diabetes, and the result shows a satisfactory AUC of 0.83. Conclusion Our approach successfully exploits template features to recognize true hypertension-related gene mentions and position features to distinguish key genes from other related genes. Templates are automatically generated and checked by biologists to minimize labor costs. Our approach integrates the

  19. A Review of Feature Extraction Software for Microarray Gene Expression Data

    PubMed Central

    Tan, Ching Siang; Ting, Wai Soon; Mohamad, Mohd Saberi; Chan, Weng Howe; Deris, Safaai; Ali Shah, Zuraini

    2014-01-01

    When gene expression data are too large to be processed, they are transformed into a reduced representation set of genes. Transforming large-scale gene expression data into a set of genes is called feature extraction. If the genes extracted are carefully chosen, this gene set can extract the relevant information from the large-scale gene expression data, allowing further analysis by using this reduced representation instead of the full size data. In this paper, we review numerous software applications that can be used for feature extraction. The software reviewed is mainly for Principal Component Analysis (PCA), Independent Component Analysis (ICA), Partial Least Squares (PLS), and Local Linear Embedding (LLE). A summary and sources of the software are provided in the last section for each feature extraction method. PMID:25250315

  20. Clinical and molecular features of young-onset colorectal cancer

    PubMed Central

    Ballester, Veroushka; Rashtak, Shahrooz; Boardman, Lisa

    2016-01-01

    Colorectal cancer (CRC) is one of the leading causes of cancer related mortality worldwide. Although young-onset CRC raises the possibility of a hereditary component, hereditary CRC syndromes only explain a minority of young-onset CRC cases. There is evidence to suggest that young-onset CRC have a different molecular profile than late-onset CRC. While the pathogenesis of young-onset CRC is well characterized in individuals with an inherited CRC syndrome, knowledge regarding the molecular features of sporadic young-onset CRC is limited. Understanding the molecular mechanisms of young-onset CRC can help us tailor specific screening and management strategies. While the incidence of late-onset CRC has been decreasing, mainly attributed to an increase in CRC screening, the incidence of young-onset CRC is increasing. Differences in the molecular biology of these tumors and low suspicion of CRC in young symptomatic individuals, may be possible explanations. Currently there is no evidence that supports that screening of average risk individuals less than 50 years of age will translate into early detection or increased survival. However, increasing understanding of the underlying molecular mechanisms of young-onset CRC could help us tailor specific screening and management strategies. The purpose of this review is to evaluate the current knowledge about young-onset CRC, its clinicopathologic features, and the newly recognized molecular alterations involved in tumor progression. PMID:26855533

  1. Clinical Features of Spontaneous Partial Healing During Mycobacterium ulcerans Infection.

    PubMed

    Marion, Estelle; Chauty, Annick; Kempf, Marie; Le Corre, Yannick; Delneste, Yves; Croue, Anne; Marsollier, Laurent

    2016-01-01

    Background.  Buruli ulcer, caused by Mycobacterium ulcerans, is a necrotizing skin disease leading to extensive cutaneous and subcutaneous destruction and functional limitations. Spontaneous healing in the absence of medical treatment occurs in rare cases, but this has not been well described in the literature. Methods.  In a retrospective case study in an area of Benin where this disease is highly endemic, we selected 26 Buruli ulcer patients presenting features of spontaneous healing from a cohort of 545 Buruli ulcer patients treated between 2010 and 2013. Results.  The 26 patients studied had a median age of 13.5 years and were predominantly male (1.4:1). Three groups of patients were defined on the basis of their spontaneous healing characteristics. The first group (12 patients) consisted of patients with an ulcer of more than 1 year's duration showing signs of healing. The second (13 patients) group contained patients with an active Buruli ulcer lesion some distance away from a first lesion that had healed spontaneously. Finally, the third group contained a single patient displaying complete healing of lesions from a nodule, without treatment and with no relapse. Conclusions.  We defined several features of spontaneous healing in Buruli ulcer patients and highlighted the difficulties associated with diagnosis and medical management. Delays in consultation contributed to the high proportion of patients with permanent sequelae and a risk of squamous cell carcinoma. Early detection and antibiotic treatment are the best ways to reduce impairments. PMID:26925431

  2. Clinical Features of Spontaneous Partial Healing During Mycobacterium ulcerans Infection

    PubMed Central

    Marion, Estelle; Chauty, Annick; Kempf, Marie; Le Corre, Yannick; Delneste, Yves; Croue, Anne; Marsollier, Laurent

    2016-01-01

    Background. Buruli ulcer, caused by Mycobacterium ulcerans, is a necrotizing skin disease leading to extensive cutaneous and subcutaneous destruction and functional limitations. Spontaneous healing in the absence of medical treatment occurs in rare cases, but this has not been well described in the literature. Methods. In a retrospective case study in an area of Benin where this disease is highly endemic, we selected 26 Buruli ulcer patients presenting features of spontaneous healing from a cohort of 545 Buruli ulcer patients treated between 2010 and 2013. Results. The 26 patients studied had a median age of 13.5 years and were predominantly male (1.4:1). Three groups of patients were defined on the basis of their spontaneous healing characteristics. The first group (12 patients) consisted of patients with an ulcer of more than 1 year′s duration showing signs of healing. The second (13 patients) group contained patients with an active Buruli ulcer lesion some distance away from a first lesion that had healed spontaneously. Finally, the third group contained a single patient displaying complete healing of lesions from a nodule, without treatment and with no relapse. Conclusions. We defined several features of spontaneous healing in Buruli ulcer patients and highlighted the difficulties associated with diagnosis and medical management. Delays in consultation contributed to the high proportion of patients with permanent sequelae and a risk of squamous cell carcinoma. Early detection and antibiotic treatment are the best ways to reduce impairments. PMID:26925431

  3. Clinical Features of Alzheimer Disease With and Without Lewy Bodies

    PubMed Central

    Chung, Eun Joo; Babulal, Ganesh M.; Monsell, Sarah E.; Cairns, Nigel J.; Roe, Catherine M.; Morris, John C.

    2015-01-01

    IMPORTANCE Lewy bodies are a frequent coexisting pathology in late-onset Alzheimer disease (AD). Previous studies have examined the contribution of Lewy bodies to the clinical phenotype of late-onset AD with variable findings. OBJECTIVE To determine whether the presence of Lewy body pathology influences the clinical phenotype and progression of symptoms in longitudinally assessed participants with AD. DESIGN, SETTING, AND PARTICIPANTS Retrospective clinical and pathological cohort study of 531 deceased participants who met the neuropathologic criteria for intermediate or high likelihood of AD according to the National Institute on Aging–Ronald Reagan Institute guidelines for the neuropathologic diagnosis of AD. All participants had a clinical assessment within 2 years of death. The data were obtained from 34 AD centers maintained by the National Alzheimer Coordinating Center and spanned from September 12, 2005, to April 30, 2013. EXPOSURES Standardized neuropathologic assessment and then brain autopsy after death. MAIN OUTCOMES AND MEASURES Clinical and neuropsychiatric test scores. RESULTS The mean (SD) age at death was statistically significantly younger for participants who had AD with Lewy bodies (77.9 [9.5] years) than for participants who had AD without Lewy bodies (80.2 [11.1] years) (P = .01). The mean (SD) age at onset of dementia symptoms was also younger for participants who had AD with Lewy bodies (70.0 [9.9] years) than for participants who had AD without Lewy bodies (72.2 [12.3] years) (P = .03). More men than women had AD with Lewy bodies (P = .01). The frequency of having at least 1 APOE ε4 allele was higher for participants who had AD with Lewy bodies than for participants who had AD without Lewy bodies (P = .03). After adjusting for age, sex, education, frequency of plaques (neuritic and diffuse), and tangle stage, we found that participants who had AD with Lewy bodies had a statistically significantly higher mean (SD) Neuropsychiatric

  4. Clinical Features and Treatment of Distal Intracranial Aneurysms.

    PubMed

    Mou, Kejie; Zhou, Zheng; Yin, Jinbo; Yang, Hui; Liu, Jun

    2016-05-01

    To analyze the clinical characteristics, therapies, and outcomes of distal intracranial aneurysms, the authors retrospectively studied the clinical and imaging data of 18 patients with distal intracranial aneurysms. There were 10 males and 8 females, aged from 11 months to 59 years (mean, 40.4 ± 11.4 years). All patients were diagnosed by digital subtract angiography. Aneurysm locations were as follows: distal anterior cerebral artery (n = 5), distal middle cerebral artery (n = 2), distal posterior cerebral artery (n = 6), distal posterior inferior cerebellar artery (n = 3), distal anterior inferior cerebellar artery (n = 1), and distal superior cerebellar artery (n = 1). Endovascular embolization was performed on 16 patients, including coil embolization on 10 patients and embolization using Glubran 2 surgical glue on 6 patients, and 7 of the 16 patients also underwent parent artery occlusion. Aneurysms were all completely embolized at the first phase for these 16 patients. The other 2 patients underwent craniotomy with hematoma evacuation and complete aneurysm clipping. Postoperatively, 14 patients showed a good recovery, 2 patients had neurological deficits, 1 patient had seizures and was managed with drugs, 1 patient developed hydrocephalus, and a ventriculo-peritoneal shunt was performed. Follow-up angiographies showed no aneurysm recurrence. Clinical manifestations of distal intracranial aneurysms are varied. Their treatment should follow the principle of individual choice. Endovascular embolization is an effective way to treat distal intracranial aneurysms; and for those with intracranial hematoma, craniotomy with hematoma evacuation and aneurysm clipping may be a feasible treatment. PMID:26982109

  5. First Chikungunya Outbreak in Suriname; Clinical and Epidemiological Features

    PubMed Central

    van Genderen, Farah T.; Krishnadath, Ingrid; Sno, Rachel; Grunberg, Meritha G.; Zijlmans, Wilco; Adhin, Malti R.

    2016-01-01

    Background In June 2014, Suriname faced the first Chikungunya outbreak. Since international reports mostly focus on hospitalized patients, the least affected group, a study was conducted to describe clinical characteristics of mainly outpatients including children. In addition, the cumulative incidence of this first epidemic was investigated. Methodology During August and September 2014, clinically suspected Chikungunya cases were included in a prospective follow-up study. Blood specimens were collected and tested for viral RNA presence. Detailed clinical information was gathered through multiple telephone surveys until day 180. In addition, a three stage household-based cluster with a cross-sectional design was conducted in October, December 2014 and March 2015 to assess the cumulative incidence. Principal Findings Sixty-eight percent of symptomatic patients tested positive for Chikungunya virus (CHIKV). Arthralgia and pain in the fingers were distinctive for viremic CHIKV infected patients. Viremic CHIKV infected children (≤12 years) characteristically displayed headache and vomiting, while arthralgia was less common at onset. The disease was cleared within seven days by 20% of the patients, while 22% of the viremic CHIKV infected patients, mostly women and elderly reported persistent arthralgia at day 180. The extrapolated cumulative CHIKV incidence in Paramaribo was 249 cases per 1000 persons, based on CHIKV self-reported cases in 53.1% of the households and 90.4% IgG detected in a subset of self-reported CHIKV+ persons. CHIKV peaked in the dry season and a drastic decrease in CHIKV patients coincided with a governmental campaign to reduce mosquito breeding sites. Conclusions/Significance This study revealed that persistent arthralgia was a concern, but occurred less frequently in an outpatient setting. The data support a less severe pathological outcome for Caribbean CHIKV infections. This study augments incidence data available for first outbreaks in the

  6. Auditory dysfunction in schizophrenia: integrating clinical and basic features

    PubMed Central

    Javitt, Daniel C.; Sweet, Robert A.

    2015-01-01

    Schizophrenia is a complex neuropsychiatric disorder that is associated with persistent psychosocial disability in affected individuals. Although studies of schizophrenia have traditionally focused on deficits in higher-order processes such as working memory and executive function, there is an increasing realization that, in this disorder, deficits can be found throughout the cortex and are manifest even at the level of early sensory processing. These deficits are highly amenable to translational investigation and represent potential novel targets for clinical intervention. Deficits, moreover, have been linked to specific structural abnormalities in post-mortem auditory cortex tissue from individuals with schizophrenia, providing unique insights into underlying pathophysiological mechanisms. PMID:26289573

  7. Venous compression syndromes: clinical features, imaging findings and management

    PubMed Central

    Liu, R; Oliveira, G R; Ganguli, S; Kalva, S

    2013-01-01

    Extrinsic venous compression is caused by compression of the veins in tight anatomic spaces by adjacent structures, and is seen in a number of locations. Venous compression syndromes, including Paget–Schroetter syndrome, Nutcracker syndrome, May–Thurner syndrome and popliteal venous compression will be discussed. These syndromes are usually seen in young, otherwise healthy individuals, and can lead to significant overall morbidity. Aside from clinical findings and physical examination, diagnosis can be made with ultrasound, CT, or MR conventional venography. Symptoms and haemodynamic significance of the compression determine the ideal treatment method. PMID:23908347

  8. Sporadic Cerebral Amyloid Angiopathy: Pathophysiology, Neuroimaging Features, and Clinical Implications.

    PubMed

    Boulouis, Gregoire; Charidimou, Andreas; Greenberg, Steven M

    2016-06-01

    Sporadic cerebral amyloid angiopathy is a small vessel disorder defined pathologically by progressive amyloid deposition in the walls of cortical and leptomeningeal vessels resulting from disruption of a complex balance between production, circulation, and clearance of amyloid-β peptide (Aβ) in the brain. Cerebral amyloid angiopathy is a major cause of lobar symptomatic intracerebral hemorrhage, transient focal neurologic episodes, and a key contributor to vascular cognitive impairment. The mechanisms and consequences of amyloid-β deposition at the pathological level and its neuroimaging manifestations, clinical consequences, and implications for patient care are addressed in this review. PMID:27214698

  9. Unusual Phenotypic Features in a Patient with a Novel Splice Mutation in the GHRHR Gene

    PubMed Central

    Hilal, Latifa; Hajaji, Yassir; Vie-Luton, Marie-Pierre; Ajaltouni, Zeina; Benazzouz, Bouchra; Chana, Maha; Chraïbi, Adelmajid; Kadiri, Abdelkrim; Amselem, Serge; Sobrier, Marie-Laure

    2008-01-01

    Isolated growth hormone deficiency (IGHD) may be of genetic origin. One of the few genes involved in that condition encodes the growth hormone releasing hormone receptor (GHRHR) that, through its ligand (GHRH), plays a pivotal role in the GH synthesis and secretion by the pituitary. Our objective is to describe the phenotype of two siblings born to a consanguineous union presenting with short stature (IGHD) and Magnetic Resonance Imaging (MRI) abnormalities, and to identify the molecular basis of this condition. Our main outcome measures were clinical and endocrinological investigations, MRI of the pituitary region, study of the GHRHR gene sequence and transcripts. In both patients, the severe growth retardation (−5SD) was combined with anterior pituitary hypoplasia. In addition to these classical phenotypic features for IGHD, one of the patients had a Chiari I malformation, an arachnoid cyst, and a dysmorphic anterior pituitary. A homozygous sequence variation in the consensus donor splice site of intron 1 (IVS1 + 2T > G) of the GHRHR gene was identified in both patients. Using in vitro transcription assay, we showed that this mutation results in abnormal splicing of GHRHR transcripts. In this report, which broadens the phenotype associated with GHRHR defects, we discuss the possible role of the GHRHR in the proper development of extrapituitary structures, through a mechanism that could be direct or secondary to severe GH deficiency. PMID:18297129

  10. Unusual phenotypic features in a patient with a novel splice mutation in the GHRHR gene.

    PubMed

    Hilal, Latifa; Hajaji, Yassir; Vie-Luton, Marie-Pierre; Ajaltouni, Zeina; Benazzouz, Bouchra; Chana, Maha; Chraïbi, Adelmajid; Kadiri, Abdelkrim; Amselem, Serge; Sobrier, Marie-Laure

    2008-01-01

    Isolated growth hormone deficiency (IGHD) may be of genetic origin. One of the few genes involved in that condition encodes the growth hormone releasing hormone receptor (GHRHR) that, through its ligand (GHRH), plays a pivotal role in the GH synthesis and secretion by the pituitary. Our objective is to describe the phenotype of two siblings born to a consanguineous union presenting with short stature (IGHD) and Magnetic Resonance Imaging (MRI) abnormalities, and to identify the molecular basis of this condition. Our main outcome measures were clinical and endocrinological investigations, MRI of the pituitary region, study of the GHRHR gene sequence and transcripts. In both patients, the severe growth retardation (-5SD) was combined with anterior pituitary hypoplasia. In addition to these classical phenotypic features for IGHD, one of the patients had a Chiari I malformation, an arachnoid cyst, and a dysmorphic anterior pituitary. A homozygous sequence variation in the consensus donor splice site of intron 1 (IVS1 + 2T > G) of the GHRHR gene was identified in both patients. Using in vitro transcription assay, we showed that this mutation results in abnormal splicing of GHRHR transcripts. In this report, which broadens the phenotype associated with GHRHR defects, we discuss the possible role of the GHRHR in the proper development of extrapituitary structures, through a mechanism that could be direct or secondary to severe GH deficiency. PMID:18297129

  11. The clinical features of thin basement membrane nephropathy.

    PubMed

    Gregory, Martin C

    2005-05-01

    Thin basement membrane nephropathy (TBMN) is a common, lifelong condition affecting the kidneys that is characterized by microscopic glomerular hematuria, minimal or no proteinuria, and normal renal function. It often is discovered incidentally, and usually has an excellent prognosis. Many cases are familial and show autosomal-dominant inheritance. The defining characteristic is a glomerular basement membrane (GBM) that is thinned to about half its normal thickness on ultrastructural examination of the renal biopsy specimen. However, occasionally patients with TBMN develop marked proteinuria or renal impairment. It is unclear whether individuals with TBMN and impaired renal function represent part of the spectrum of TBMN associated with heterozygous COL4A3 or COL4A4 mutations, or if their disease is caused by mutations of other genes, or whether it is caused by a second coexistent renal lesion or is misdiagnosed Alport syndrome. PMID:15880323

  12. [Clinical features and pathogenesis of Yusho (PCB poisoning)].

    PubMed

    Asahi, M

    1993-03-01

    The occurrence and progress of Yusho (PCB mass poisoning) is briefly described. Various investigative studies on Yusho are also briefly reviewed. Yusho occurred in the northern district of Kyushu Island in 1968. A specific product of rice oil used for food was accidentally contaminated with PCB during its manufacturing process and consequently, the customers who ate it showed severe intoxication symptoms. Major clinical symptoms of Yusho were acneiform eruptions and circumscribed pigmentation. These skin and mucous membrane eruptions, because of their appearance, caused severe mental suffering for the patients. The government-authorized patients amounted to 1,860. These symptoms have gradually declined with the passing of years and presently the principal clinical problems are only various subjective complaints. At first, it was naturally thought that the causative agent of Yusho was PCB (Kanechlor 400) itself. However, it was found later that the causative rice oil contained PCDF (polychlorodibenzofuran) and PCQ (polychloroquaterphenyl) which were proved to be formed during the heating process used in the deodorization of the oil. PCDFs show, in animal studies, a high toxicity and therefore its role for the pathogenesis of Yusho is seriously evaluated in spite of its rather small contaminating amount. On the other hand, PCQs are recognized as the specific marker of Yusho, since almost no PCQ is a general environmental pollution substance. PMID:8480091

  13. Metastatic tumors to the stomach: Clinical and endoscopic features

    PubMed Central

    Palma, Giovanni D De; Masone, Stefania; Rega, Maria; Simeoli, Immacolata; Donisi, Mario; Addeo, Pietro; Iannone, Loredana; Pilone, Vincenzo; Persico, Giovanni

    2006-01-01

    AIM: To evaluate the clinical and endoscopic patterns in a large series of patients with metastatic tumors in the stomach. METHODS: A total of 64 patients with gastric meta-stases from solid malignant tumors were retros-pectively examined between 1990 and 2005. The clinicopathological findings were reviewed along with tumor characteristics such as endoscopic pattern, location, size and origin of the primary sites. RESULTS: Common indications for endoscopy were anemia, bleeding and epigastric pain. Metastases presented as solitary (62.5%) or multiple (37.5%) tumors were mainly located in the middle or upper third of stomach. The main primary metastatic tumors were from breast and lung cancer and malignant melanoma. CONCLUSION: As the prognosis of cancer patients has been improving gradually, gastrointestinal (GI) metastases will be encountered more often. Endoscopic examinations should be conducted carefully in patients with malignancies, and endoscopic biopsies and information on the patient’s clinical history are useful for correct diagnosis of gastric metastases. PMID:17143949

  14. Nontyphoid salmonella infection: microbiology, clinical features, and antimicrobial therapy.

    PubMed

    Chen, Hung-Ming; Wang, Yue; Su, Lin-Hui; Chiu, Cheng-Hsun

    2013-06-01

    Nontyphoid Salmonella is the most common bacterial pathogen causing gastrointestinal infection worldwide. Most nontyphoid Salmonella infection is limited to uncomplicated gastroenteritis that seldom requires antimicrobial treatment. Nevertheless, invasive infections, such as bacteremia, osteomyelitis, and meningitis, may occur and require antimicrobial therapy. Continuous genetic and genomic evolution in Salmonella leading to increased virulence and resistance to multiple drugs are of significant public health concern. Two major changes in the epidemiology of nontyphoid salmonellosis in Europe and in the USA occurred in the second half of the 20(th) century: the emergence of foodborne human infections caused by Salmonella enterica serotype Enteriditis and by multidrug-resistant strains of Salmonella enterica serotype Typhimurium. In the 21(st) century, a worsening situation is the increasing resistance to fluoroquinolones and third-generation cephalosporins in nontyphoid Salmonella. Clinical isolates showing carbapenem resistance also have been identified. Although antimicrobial therapy is usually not indicated for uncomplicated Salmonella gastroenteritis, recent studies indicated that a short-course ceftriaxone therapy (3-5 days) for patients with severe gastroenteritis would lead to a faster clinical recovery. Continuous surveillance of Salmonella in both humans and animals is mandatory. A better understanding of the mechanisms that lead to the emergence of antimicrobial resistance in Salmonella may help in the devising of better interventional strategies to reduce the spread of resistant Salmonella between humans and reservoirs along the food chain. PMID:23597525

  15. Intracranial Hypertension in Children: Etiologies, Clinical Features, and Outcome.

    PubMed

    Masri, Amira; Jaafar, Amani; Noman, Rasha; Gharaibeh, Almutez; Ababneh, Osama H

    2015-10-01

    This retrospective study aimed to describe the clinical presentations, possible causes, and outcomes of children with idiopathic intracranial hypertension who presented to the authors' clinic. The mean age at onset of symptoms in the authors' cohort of 19 children was 6 years (range: 7 months to 12 years). Most patients (90%) were under 11 years old and (84.2%) symptomatic. The probable cause was identified in 7/19 (37.0%) patients. The most common cause was vitamin D deficiency (26.3%). Other associated probably coincidental comorbidities included sinusitis (5/19, 26.3%), hypophosphatasia (1/19), Pyle disease (1/19), and measles vaccine (1/19). Apart from 2 patients who required lumboperitoneal shunt, the cerebrospinal fluid pressure returned to normal in all patients within a period of 6 weeks to 1 year (average, 5 months). Of those who followed up with the authors' ophthalmologist, 30.7% developed optic atrophy or pallor; 75% of these patients had previous ocular comorbidities. PMID:25762586

  16. The depressed alcoholic. Clinical features and medical management.

    PubMed

    Petty, F

    1992-07-01

    A relationship between depression and alcoholism has long been postulated. A review of prior research studies reveals that though patients with depression do not appear to develop alcoholism to any great extent, recently detoxified alcoholics have a depressive syndrome about 20% of the time. This cannot be accounted for readily from data on family studies or genetic studies, which generally suggest that alcoholism and depression are two independent illnesses, albeit both quite common. Clinically, depressed alcoholics resemble alcoholics more than they resemble depressives. The clinical course of depression when it coexists with alcoholism is generally benign and self-limited, with most patients becoming euthymic over the course of 2-4 weeks without specific antidepressant treatment. In some depressed alcoholics, however, a more chronic depression persists, and may predict a worse outcome for the alcoholism. Treatment of depression in alcoholics should be initially conservative. Tricyclic and other antidepressants should be used with extreme care as they may potentiate toxic effects of alcohol. PMID:1505747

  17. Porokeratoses: an update of clinical, aetiopathogenic and therapeutic features.

    PubMed

    Kanitakis, Jean

    2014-01-01

    Porokeratoses represent a group of uncommon, acquired or hereditary dermatoses, due to a keratinization disorder whose origin is still unclear; they could be due to the expansion of a clone of abnormal epidermal keratinocytes. Several clinical forms exist, of which the most common is disseminated superficial actinic porokeratosis; other forms include Mibelli, disseminated superficial, linear, palmoplantaris punctata and palmaris, plantaris et disseminata. These may coexist in the same patient or in different members of the same family. Porokeratoses manifest clinically with annular or linear, well-circumscribed keratotic plaques and share a common histological hallmark, the cornoid lamella, a vertical stack of parakeratotic corneocytes within the horny layer resting on a shallow depression of the underlying epidermis. Porokeratoses may be seen in the setting of various immunodeficiencies, namely in organ-transplant recipients, in whom the course of the disease may parallel the degree of immunosuppression. The overall prognosis of porokeratoses is favourable but is shadowed by the possibility of malignant transformation of the lesions (usually into squamous cell carcinoma); this happens in less than 10% of cases but may prove fatal. Although several surgical or medical (local or systemic) treatments have been tried, none of them has shown consistent and long-term efficacy. PMID:25115203

  18. Clinical features and management of organic acidemias in Japan.

    PubMed

    Fujisawa, Daisuke; Nakamura, Kimitoshi; Mitsubuchi, Hiroshi; Ohura, Toshihiro; Shigematsu, Yosuke; Yorifuji, Tohru; Kasahara, Mureo; Horikawa, Reiko; Endo, Fumio

    2013-12-01

    Organic acidemias (OAs) are rare inborn errors of metabolism. The clinical presentations of methylmalonic acidemia (MMA) and propionic acidemia (PA) in Japan have not yet been examined in detail. We aimed to investigate the clinical presentations of OAs in Japan and evaluate current therapies for improving long-term outcomes, especially in MMA and PA cases. Questionnaires were sent to 928 institutions in 2009 inquiring about OAs, and secondary questionnaires were sent to those who confirmed that they had diagnosed and/or treated such cases; 119 cases were eventually included for analysis. In Japan, the majority of OAs was MMA, which was associated with a high mortality rate. The survival rates at 20 years of age in vitamin B12-unresponsive MMA, vitamin B12-responsive MMA and PA patients were 69.8%, 94.4% and 95.8%, respectively. Factors associated with mortality in MMA were failure to thrive, hypoglycemia and pancreatitis. Factors associated with mental retardation in vitamin B12-unresponsive MMA, vitamin B12-responsive MMA, and PA were seizure and liver dysfunction, seizure and failure to thrive, and failure to thrive, respectively. We advocated that avoiding failure to thrive due to too restricted protein diet, hypoglycemia and pancreatitis associated with mortality lead to improve outcome, especially in vitamin B12-unresponsive MMA patients. PMID:24067294

  19. Stress fractures: pathophysiology, clinical presentation, imaging features, and treatment options.

    PubMed

    Matcuk, George R; Mahanty, Scott R; Skalski, Matthew R; Patel, Dakshesh B; White, Eric A; Gottsegen, Christopher J

    2016-08-01

    Stress fracture, in its most inclusive description, includes both fatigue and insufficiency fracture. Fatigue fractures, sometimes equated with the term "stress fractures," are most common in runners and other athletes and typically occur in the lower extremities. These fractures are the result of abnormal, cyclical loading on normal bone leading to local cortical resorption and fracture. Insufficiency fractures are common in elderly populations, secondary to osteoporosis, and are typically located in and around the pelvis. They are a result of normal or traumatic loading on abnormal bone. Subchondral insufficiency fractures of the hip or knee may cause acute pain that may present in the emergency setting. Medial tibial stress syndrome is a type of stress injury of the tibia related to activity and is a clinical syndrome encompassing a range of injuries from stress edema to frank-displaced fracture. Atypical subtrochanteric femoral fracture associated with long-term bisphosphonate therapy is also a recently discovered entity that needs early recognition to prevent progression to a complete fracture. Imaging recommendations for evaluation of stress fractures include initial plain radiographs followed, if necessary, by magnetic resonance imaging (MRI), which is preferred over computed tomography (CT) and bone scintigraphy. Radiographs are the first-line modality and may reveal linear sclerosis and periosteal reaction prior to the development of a frank fracture. MRI is highly sensitive with findings ranging from periosteal edema to bone marrow and intracortical signal abnormality. Additionally, a brief description of relevant clinical management of stress fractures is included. PMID:27002328

  20. Classifying types of DIC: clinical features and animal models.

    PubMed

    Asakura, Hidesaku

    2016-04-01

    Disseminated intravascular coagulation (DIC) is a pathological state in which varying degrees of fibrinolytic activation are seen simultaneously as systemic, persistent, and marked coagulation activation in the presence of an underlying disease. Suppressed-fibrinolytic-type DIC usually develops in patients with sepsis. Coagulation activation is severe, while fibrinolytic activation is mild. Enhanced-fibrinolytic-type DIC usually occurs with acute promyelocytic leukemia (APL). Both coagulation activation and fibrinolytic activation are severe in affected patients. Balanced-fibrinolytic-type DIC is usually seen in patients with solid tumors, and has a pathogenesis intermediate between those of the two aforementioned types. In animal DIC models, lipopolysaccharide (LPS)-induced forms of DIC are similar to suppressed-fibrinolytic-type DIC, whereas models of tissue factor (TF)-induced DIC have features similar to those of enhanced-fibrinolytic/balanced-fibrinolytic DIC. We are moving in the direction of more appropriate selection of treatment based on DIC type. PMID:27169441

  1. Cutaneous invasion from sarcomatoid urothelial carcinoma: clinical and dermatopathologic features*

    PubMed Central

    Bernardes Filho, Fred; de Melo, Alessandro Severo Alves; Pires, Andréa Rodriguez Cordovil; Lupi, Omar; Neves, Daniel Gama das; da Cruz, Margareth Fernandes; Kac, Bernard Kawa

    2016-01-01

    In Brazil, without considering the non-melanoma skin tumors, bladder cancer in men is the eighth most common, and the urothelial carcinoma or transitional cell carcinoma is the most common among these. Cutaneous metastases from urothelial neoplasms appear as single or multiple erythematous, infiltrated nodules or plaques, and like other cases of distant disease, it is indicative of poor prognosis. The invasive urothelial carcinoma is recognized for its ability to present divergent differentiation and morphological variants. The sarcomatoid urothelial carcinoma is a rare cancer that consists of two different components: one composed of epithelial tissue and the other with sarcomatoid features of mesenchymal origin. The authors describe a case of cutaneous metastasis of sarcomatoid urothelial carcinoma in a 63-year-old male patient. PMID:26982782

  2. Detecting Key Structural Features within Highly Recombined Genes

    PubMed Central

    Wertz, John E; McGregor, Karen F; Bessen, Debra E

    2007-01-01

    Many microorganisms exhibit high levels of intragenic recombination following horizontal gene transfer events. Furthermore, many microbial genes are subject to strong diversifying selection as part of the pathogenic process. A multiple sequence alignment is an essential starting point for many of the tools that provide fundamental insights on gene structure and evolution, such as phylogenetics; however, an accurate alignment is not always possible to attain. In this study, a new analytic approach was developed in order to better quantify the genetic organization of highly diversified genes whose alleles do not align. This BLAST-based method, denoted BLAST Miner, employs an iterative process that places short segments of highly similar sequence into discrete datasets that are designated “modules.” The relative positions of modules along the length of the genes, and their frequency of occurrence, are used to identify sequence duplications, insertions, and rearrangements. Partial alleles of sof from Streptococcus pyogenes, encoding a surface protein under host immune selection, were analyzed for module content. High-frequency Modules 6 and 13 were identified and examined in depth. Nucleotide sequences corresponding to both modules contain numerous duplications and inverted repeats, whereby many codons form palindromic pairs. Combined with evidence for a strong codon usage bias, data suggest that Module 6 and 13 sequences are under selection to preserve their nucleic acid secondary structure. The concentration of overlapping tandem and inverted repeats within a small region of DNA is highly suggestive of a mechanistic role for Module 6 and 13 sequences in promoting aberrant recombination. Analysis of pbp2X alleles from Streptococcus pneumoniae, encoding cell wall enzymes that confer antibiotic resistance, supports the broad applicability of this tool in deciphering the genetic organization of highly recombined genes. BLAST Miner shares with phylogenetics the

  3. Clinical report of a 17q12 microdeletion with additionally unreported clinical features.

    PubMed

    Roberts, Jennifer L; Gandomi, Stephanie K; Parra, Melissa; Lu, Ira; Gau, Chia-Ling; Dasouki, Majed; Butler, Merlin G

    2014-01-01

    Copy number variations involving the 17q12 region have been associated with developmental and speech delay, autism, aggression, self-injury, biting and hitting, oppositional defiance, inappropriate language, and auditory hallucinations. We present a tall-appearing 17-year-old boy with marfanoid habitus, hypermobile joints, mild scoliosis, pectus deformity, widely spaced nipples, pes cavus, autism spectrum disorder, intellectual disability, and psychiatric manifestations including physical and verbal aggression, obsessive-compulsive behaviors, and oppositional defiance. An echocardiogram showed borderline increased aortic root size. An abdominal ultrasound revealed a small pancreas, mild splenomegaly with a 1.3 cm accessory splenule, and normal kidneys and liver. A testing panel for Marfan, aneurysm, and related disorders was negative. Subsequently, a 400 K array-based comparative genomic hybridization (aCGH) + SNP analysis was performed which identified a de novo suspected pathogenic deletion on chromosome 17q12 encompassing 28 genes. Despite the limited number of cases described in the literature with 17q12 rearrangements, our proband's phenotypic features both overlap and expand on previously reported cases. Since syndrome-specific DNA sequencing studies failed to provide an explanation for this patient's unusual habitus, we postulate that this case represents an expansion of the 17q12 microdeletion phenotype. Further analysis of the deleted interval is recommended for new genotype-phenotype correlations. PMID:24991439

  4. Review: Clinical aspects of hereditary DNA Mismatch repair gene mutations.

    PubMed

    Sijmons, Rolf H; Hofstra, Robert M W

    2016-02-01

    Inherited mutations of the DNA Mismatch repair genes MLH1, MSH2, MSH6 and PMS2 can result in two hereditary tumor syndromes: the adult-onset autosomal dominant Lynch syndrome, previously referred to as Hereditary Non-Polyposis Colorectal Cancer (HNPCC) and the childhood-onset autosomal recessive Constitutional Mismatch Repair Deficiency syndrome. Both conditions are important to recognize clinically as their identification has direct consequences for clinical management and allows targeted preventive actions in mutation carriers. Lynch syndrome is one of the more common adult-onset hereditary tumor syndromes, with thousands of patients reported to date. Its tumor spectrum is well established and includes colorectal cancer, endometrial cancer and a range of other cancer types. However, surveillance for cancers other than colorectal cancer is still of uncertain value. Prophylactic surgery, especially for the uterus and its adnexa is an option in female mutation carriers. Chemoprevention of colorectal cancer with aspirin is actively being investigated in this syndrome and shows promising results. In contrast, the Constitutional Mismatch Repair Deficiency syndrome is rare, features a wide spectrum of childhood onset cancers, many of which are brain tumors with high mortality rates. Future studies are very much needed to improve the care for patients with this severe disorder. PMID:26746812

  5. Fluorescein angiographic findings and clinical features in Fuchs' uveitis.

    PubMed

    Bouchenaki, Nadia; Herbort, Carl P

    2010-10-01

    Fuchs' uveitis is very often diagnosed with substantial delay, which is at the origin of deleterious effects such as unnecessary treatment and its consequences. The aim of this study was to analyse the type and frequency of posterior inflammatory and fluorescein angiographic signs in Fuchs' uveitis in conjunction with other clinical signs. Patients seen at the Centre for Ophthalmic Specialised Care (COS) in Lausanne and the Memorial A. de Rothschild, Clinique Générale-Beaulieu in Geneva between 1995 and 2008 with the diagnosis of Fuchs' uveitis and who had undergone a fundus fluorescein angiography (FFA) were analysed. In addition to FFA signs, the data collected included age, gender, initial and final visual acuities, clinical findings at presentation, mean diagnostic delay and ocular complications. Between 1995 and 2008, 105 patients seen in our centres in Lausanne and Geneva were diagnosed with Fuchs' uveitis. Forty of them (38.1%) had undergone at least one FFA. One patient was excluded because of a concomittant diagnosis of multiple sclerosis. In 28 of 39 patients (71.2%) diagnosis was not reached at presentation with a mean diagnosis delay of 3.67 ± 4.86 years (range: 1 month-24 years). The original erroneous diagnosis was intermediate uveitis in 16 patients (57.1%), posterior uveitis in two patients (7.1%), panuveitis in four patients (14.3%) and anterior granulomatous uveitis in six patients (21.4%). Fluorescein angiography demonstrated the presence of disc hyperfluorescence in 43/44 eyes (97.7%), sectorial peripheral retinal vascular leaking in 6/44 eyes (13.6%) and cystoid macular oedema in 4/44 eyes (9.1%), all of which were seen in eyes having undergone cataract surgery. Fuchs' uveitis was bilateral in 5/39 patients (12.8%). The most frequent clinical signs were vitritis in 42/44 eyes (95.5%), stellate keratic precipitates in 41 eyes (93.2%), posterior subcapsular opacities or cataract in 19 eyes (43.2%), and heterochromia in 19 eyes (43.2%). Fuchs

  6. Clinical Features of Spinal Cord Hemangioblastoma in a Dog

    PubMed Central

    Michaels, Jennifer; Thomas, William; Ferguson, Sylvia; Hecht, Silke

    2015-01-01

    A 2-year-old male, intact Yorkshire terrier presented with a 1-month history of progressive paraparesis. Neurological examination revealed paraplegia with absent deep pain perception, decreased right pelvic limb withdrawal reflex, and lumbar pain consistent with an L4–S2 neurolocalization. Magnetic resonance imaging (MRI) showed a single, well-demarcated, intramedullary mass centered over the L3–4 disk space. A hemilaminectomy was performed, and the mass was removed en bloc. Histopathological evaluation was consistent with a hemangioblastoma. Follow-up MRI 9 months after surgery showed no evidence of tumor recurrence, and the dog was ambulatory paraparetic at that time. This case is consistent with a previous histopathological report of spinal cord hemangioblastoma in a dog and provides additional clinical information regarding diagnosis, treatment, and outcome associated with this tumor type. PMID:26664967

  7. Anatomical features and clinical relevance of a persistent trigeminal artery

    PubMed Central

    Alcalá-Cerra, Gabriel; Tubbs, R S; Niño-Hernández, Lucía M

    2012-01-01

    Background: Although persistent trigeminal artery (PTA) is uncommonly identified, knowledge of this structure is essential for clinicians who interpret cranial imaging, perform invasive studies of the cerebral vasculature, and operate this region. Methods: A review of the medical literature using standard search engines was performed to locate articles regarding the PTA, with special attention with anatomical descriptions. Results: Although anatomical reports of PTA anatomy are very scarce, those were analyzed to describe in detail the current knowledge about its anatomical relationships and variants. Additionally, the embryology, classification, clinical implications, and imaging modalities of this vessel are extensively discussed. Conclusions: Through a comprehensive review of isolated reports of the PTA, the clinician can better understand and treat patients with such an anatomical derailment. PMID:23087827

  8. Clinical features in adult patient with Wolf-Hirschhorn syndrome.

    PubMed

    Martínez-Quintana, E; Rodríguez-González, F

    2014-06-01

    The Wolf-Hirschhorn syndrome (WHS) encompasses deletions at the distal part of the short arm of one chromosome 4 (4p16 region). Clinical signs frequently include a typical facial appearance, mental retardation, intrauterine and postnatal growth retardation, hypotonia with decreased muscle bulk and seizures besides congenital heart malformations, midline defects, urinary tract malformations and brain, hearing and ophthalmologic malformations. Pathogenesis of WHS is multigenic and many factors are involved in prediction of prognosis such as extent of deletion, the occurrence of severe chromosome anomalies, the severe of seizures, the existence of serious internal, mainly cardiac, abnormalities and the degree of mental retardation. The phenotype of adult with WHS is in general similar to that of childhood being facial dysmorphism, growth retardation and mental retardation the rule in both adults and children. Avoid long-term complications and provide rehabilitation programs and genetic counseling may be essential in these patients. PMID:24656633

  9. Clinical features, investigation and treatment of post-traumatic syringomyelia.

    PubMed Central

    Shannon, N; Symon, L; Logue, V; Cull, D; Kang, J; Kendall, B

    1981-01-01

    Thirteen patients who sustained spinal cord trauma causing persisting disability, developed new symptoms, the chief one of which was severe pain unrelieved by analgesics. The clinical diagnosis of post traumatic syringomyelia was confirmed in each case by means of myelography, as well as endomyelography in seven patients. In every case exploration of the spinal cord syrinx was performed. Ten patients were troubled by severe pain while three patients were mainly subject to altered sensation in the upper limbs. Of the six patients who had initially sustained complete cord transections, three were treated by cord transection and three were treated by syringostomy. The seven patients who sustained incomplete cord lesions were all treated by syringostomy. The patients who initially sustained incomplete sensory motor spinal cord damage had a better symptomatic response to surgery than hose who had sustained a complete spinal cord lesion. The ten patients whose main symptom was severe pain were completely relieved of their symptoms by surgery. Images PMID:7205304

  10. Calibre Persistent Labial Artery: Clinical Features and Immunohistochemistry Diagnosis.

    PubMed

    Santagata, M; Maglione, M; Colella, G; D'Amato, S

    2015-09-01

    Calibre persistent labial artery (CPLA) usually presents as an asymptomatic papule on the lower lip and can be easily misdiagnosed as a mucocele, haemangioma, venous lake, varix or fibroma. When it is ulcerated, squamous cell carcinoma is the most usual differential diagnosis. Here, we report a case of a 25-year-old woman with no previous relevant medical history who presented with a complaint of an asymptomatic, non-ulcerated, progressively growing nodule (over the last 5 months) on the upper lip. In this case, the diagnosis was made clinically and confirmed by immunohistochemical analysis. We conclude that clinicians should be aware of CPLA and it should be included in the differential diagnosis of labial mucosal papules. Sometimes, the immunohistochemical analysis is necessary to make a correct diagnosis. PMID:26225087

  11. MERRF: Clinical features, muscle biopsy and molecular genetics in Brazilian patients.

    PubMed

    Lorenzoni, Paulo José; Scola, Rosana H; Kay, Cláudia S Kamoi; Arndt, Raquel C; Silvado, Carlos E; Werneck, Lineu C

    2011-05-01

    Myoclonic epilepsy with ragged red fibers (MERRF) is a mitochondrial disease that is characterized by myoclonic epilepsy with ragged red fibers (RRF) in muscle biopsies. The aim of this study was to analyze Brazilian patients with MERRF. Six patients with MERRF were studied and correlations between clinical findings, laboratory data, electrophysiology, histology and molecular features were examined. We found that blood lactate was increased in four patients. Electroencephalogram studies revealed generalized epileptiform discharges in five patients and generalized photoparoxysmal responses during intermittent photic stimulation in two patients. Muscle biopsies showed RRF in all patients using modified Gomori-trichrome and succinate dehydrogenase stains. Cytochrome c oxidase (COX) stain analysis indicated deficient activity in five patients and subsarcolemmal accumulation in one patient. Molecular analysis of the tRNA(Lys) gene with PCR/RFLP and direct sequencing showed the A8344G mutation of mtDNA in five patients. The presence of RRFs and COX deficiencies in muscle biopsies often confirmed the MERRF diagnosis. We conclude that molecular analysis of the tRNA(Lys) gene is an important criterion to help confirm the MERRF diagnosis. Furthermore, based on the findings of this study, we suggest a revision of the main characteristics of this disease. PMID:21303704

  12. Severe scrub typhus infection: Clinical features, diagnostic challenges and management.

    PubMed

    Peter, John Victor; Sudarsan, Thomas I; Prakash, John Anthony J; Varghese, George M

    2015-08-01

    Scrub typhus infection is an important cause of acute undifferentiated fever in South East Asia. The clinical picture is characterized by sudden onset fever with chills and non-specific symptoms that include headache, myalgia, sweating and vomiting. The presence of an eschar, in about half the patients with proven scrub typhus infection and usually seen in the axilla, groin or inguinal region, is characteristic of scrub typhus. Common laboratory findings are elevated liver transaminases, thrombocytopenia and leukocytosis. About a third of patients admitted to hospital with scrub typhus infection have evidence of organ dysfunction that may include respiratory failure, circulatory shock, mild renal or hepatic dysfunction, central nervous system involvement or hematological abnormalities. Since the symptoms and signs are non-specific and resemble other tropical infections like malaria, enteric fever, dengue or leptospirosis, appropriate laboratory tests are necessary to confirm diagnosis. Serological assays are the mainstay of diagnosis as they are easy to perform; the reference test is the indirect immunofluorescence assay (IFA) for the detection of IgM antibodies. However in clinical practice, the enzyme-linked immuno-sorbent assay is done due to the ease of performing this test and a good sensitivity and sensitivity when compared with the IFA. Paired samples, obtained at least two weeks apart, demonstrating a ≥ 4 fold rise in titre, is necessary for confirmation of serologic diagnosis. The mainstay of treatment is the tetracycline group of antibiotics or chloramphenicol although macrolides are used alternatively. In mild cases, recovery is complete. In severe cases with multi-organ failure, mortality may be as high as 24%. PMID:26261776

  13. Activity of quinolones against gram-positive cocci: clinical features.

    PubMed

    Giamarellou, H

    1995-01-01

    The potential role of the commercially available fluoroquinolones in the treatment of Gram-positive infections is discussed on the basis of data obtained from animal experiments and clinical trials. In respiratory tract infections, and particularly in community-acquired pneumonia, it is evident that the presently available quinolones cannot be prescribed empirically as first-line therapy because of their borderline activity against Streptococcus pneumoniae and anaerobes. Reports of pneumococcal seeding in other tissues during quinolone therapy render their administration a debatable issue. Experience in endocarditis is limited to the use of ciprofloxacin plus rifampicin in intravenous drug users with right-sided Staphylococcus aureus endocarditis. Patients with staphylococcal osteomyelitis are included among cases of other bone infections. In noncontrolled studies ciprofloxacin, ofloxacin and pefloxacin attained a staphylococcal eradication rate ranging from 70 to 100%, while the addition of rifampicin has been proven to reduce the emergence of resistant mutants during therapy. In soft tissue and skin structure infections that also involve Gram-negative bacteria, ciprofloxacin and ofloxacin eradicated 72.6 and 89% of staphylococci, respectively; however, the presence of diabetes or vascular disease compromised the success of treatment. In staphylococcal peritonitis complicating continuous ambulatory peritoneal dialysis, results with ciprofloxacin given intravenously or intraperitoneally were promising. In infections in neutropenic hosts, success of prophylaxis or therapy is still not clear, since colonisation and breakthrough bacteraemias with viridans streptococci and staphylococci have been reported. Furthermore, therapeutic results are compromised by the low response rate in Gram-positive infections. Despite the reported clinical efficacy of the newer fluoroquinolones, physicians should be alerted to the emergence of staphylococci resistant to fluoroquinolones

  14. Dorsal Tear of Triangular Fibrocartilage Complex: Clinical Features and Treatment.

    PubMed

    Abe, Yukio; Moriya, Atsushi; Tominaga, Yasuhiro; Yoshida, Koji

    2016-03-01

    Background Several different triangular fibrocartilage complex (TFCC) tear patterns have been classified through the use of wrist arthroscopy. A tear of the dorsal aspect of the TFCC has been previously reported, but it is not included in Palmer original classification. Our purpose was to describe this type of tear pattern along with the clinical presentation. Methods An isolated dorsal TFCC tear was encountered in seven wrists of six patients (three men and three women; average age was 31 years). All patients were evaluated by physical exam, X-ray, plain axial computed tomography with pronation, neutral and supination position, magnetic resonance imaging (MRI) with coronal, sagittal, and axial section and arthroscopy. Results The clinical findings varied and included the following: tenderness at the dorsoulnar aspect of the wrist was positive in all wrists, fovea sign was positive in five wrists, and tenderness at the dorsal aspect of the distal radioulnar joint was present in one wrist. Pain with forearm rotation was positive in all wrists. The ulnar head ballottement test induced pain in all wrists, whereas dorsal instability of the ulnar head was present in one wrist with this test. The ulnocarpal stress test was positive in five wrists. Axial and sagittal images on MRI revealed the dorsal tear in five wrists. All wrists were treated with an arthroscopic capsular repair. The final functional outcome at an average follow-up of 16.1 months was four excellent and one good wrist according to the modified Mayo wrist score. Conclusions The aim of this article is to describe our experiences with tears involving the dorsal aspect of the TFCC, which may be misdiagnosed if the surgeon is not cognizant of this injury. Type of study/level of evidence Diagnostic/level IV. PMID:26855835

  15. Clinical Features of Young Children Referred for Impairing Temper Outbursts

    PubMed Central

    Klein, Rachel G.; Angelosante, Aleta; Bar-Haim, Yair; Leibenluft, Ellen; Hulvershorn, Leslie; Dixon, Erica; Dodds, Alice; Spindel, Carrie

    2013-01-01

    Abstract Objective In light of the current controversy about whether severe temper outbursts are diagnostic of mania in young children, we conducted a study to characterize such children, focusing on mania and other mood disorders, emotion regulation, and parental psychiatric history. Methods Study participants included 51 5–9-year-old children with frequent, impairing outbursts (probands) and 24 non-referred controls without outbursts. Parents completed a lifetime clinical interview about their child, and rated their child's current mood and behavior. Teachers completed a behavior rating scale. To assess emotion regulation, children were administered the Balloons Game, which assesses emotion expressivity in response to frustration, under demands of high and low regulation. Parental lifetime diagnoses were ascertained in blind clinical interviews. Results No child had bipolar disorder, bipolar disorder not otherwise specified (NOS), or major depression (MDD). The most prevalent disorder was oppositional defiant disorder (88.2%), followed by attention-deficit/hyperactivity disorder (74.5%), anxiety disorders (49.0%), and non-MDD depressive disorders (33.3%). Eleven probands (21.6%) met criteria for severe mood dysregulation. During the Balloons Game, when there were no demands for self-regulation, children with severe outbursts showed reduced positive expressivity, and also showed significant deficits in controlling negative facial expressions when asked to do so. Anxiety disorders were the only diagnoses significantly elevated in probands' mothers. Conclusions Overall, young children with severe temper outbursts do not present with bipolar disorder. Rather, disruptive behavior disorders with anxiety and depressive mood are common. In children with severe outbursts, deficits in regulating emotional facial expressions may reflect deficits controlling negative affect. This work represents a first step towards elucidating mechanisms underlying severe outbursts in

  16. Correlation of IL36RN mutation with different clinical features of pustular psoriasis in Chinese patients.

    PubMed

    Wang, Ting-Shun; Chiu, Hsien-Yi; Hong, Jin-Bong; Chan, Chih-Chieh; Lin, Sung-Jan; Tsai, Tsen-Fang

    2016-01-01

    Different studies have reported various values for the percentage of patients with IL36RN mutations, and it has also been reported that the sites of these mutations differ among different ethnicities. The current study was a cross-sectional study conducted to investigate the risk factors predicting IL36RN mutation in Chinese patients with different clinical features of pustular psoriasis. 57 Han Chinese patients, including 32 with generalized pustular psoriasis, 14 with palmoplantar pustulosis, 9 with plaque-type psoriasis with pustules, and 2 with erythrodermic psoriasis, were enrolled between March 2013 and July 2014. Blood samples were collected, genomic DNA was extracted from leukocytes, and polymerase chain reaction (PCR)-based Sanger sequencing was used to analyze the coding exons and flanking introns of the IL36RN gene. The patients with generalized pustular psoriasis exhibited the highest IL36RN mutation rate (75 %) among the aforementioned patient types, with the subgroup consisting of those patients who had features of acrodermatitis continua of Hallopeau exhibiting the highest c.115+6T>C mutation rate (93.8 %). In addition, early onset, ever generalized pustular psoriasis (more than two attacks), ever acrodermatitis continua of Hallopeau, inverse psoriasis, and a family history of pustular psoriasis were associated with IL36RN mutation. The c.115+6T>C mutation was the most common and the most important variant in all subtypes of pustular psoriasis with IL36RN mutations among our sample of Chinese patients. PMID:26589685

  17. Genes associated with histopathologic features of triple negative breast tumors predict molecular subtypes.

    PubMed

    Purrington, Kristen S; Visscher, Daniel W; Wang, Chen; Yannoukakos, Drakoulis; Hamann, Ute; Nevanlinna, Heli; Cox, Angela; Giles, Graham G; Eckel-Passow, Jeanette E; Lakis, Sotiris; Kotoula, Vassiliki; Fountzilas, George; Kabisch, Maria; Rüdiger, Thomas; Heikkilä, Päivi; Blomqvist, Carl; Cross, Simon S; Southey, Melissa C; Olson, Janet E; Gilbert, Judy; Deming-Halverson, Sandra; Kosma, Veli-Matti; Clarke, Christine; Scott, Rodney; Jones, J Louise; Zheng, Wei; Mannermaa, Arto; Eccles, Diana M; Vachon, Celine M; Couch, Fergus J

    2016-05-01

    Distinct subtypes of triple negative (TN) breast cancer have been identified by tumor expression profiling. However, little is known about the relationship between histopathologic features of TN tumors, which reflect aspects of both tumor behavior and tumor microenvironment, and molecular TN subtypes. The histopathologic features of TN tumors were assessed by central review and 593 TN tumors were subjected to whole genome expression profiling using the Illumina Whole Genome DASL array. TN molecular subtypes were defined based on gene expression data associated with histopathologic features of TN tumors. Gene expression analysis yielded signatures for four TN subtypes (basal-like, androgen receptor positive, immune, and stromal) consistent with previous studies. Expression analysis also identified genes significantly associated with the 12 histological features of TN tumors. Development of signatures using these markers of histopathological features resulted in six distinct TN subtype signatures, including an additional basal-like and stromal signature. The additional basal-like subtype was distinguished by elevated expression of cell motility and glucose metabolism genes and reduced expression of immune signaling genes, whereas the additional stromal subtype was distinguished by elevated expression of immunomodulatory pathway genes. Histopathologic features that reflect heterogeneity in tumor architecture, cell structure, and tumor microenvironment are related to TN subtype. Accounting for histopathologic features in the development of gene expression signatures, six major subtypes of TN breast cancer were identified. PMID:27083182

  18. [Denial of pregnancy and neonaticide: psychopathological and clinical features].

    PubMed

    Seigneurie, A-S; Limosin, F

    2012-11-01

    Pregnancy denial and neonaticide have recently received media coverage following a series of French cases of neonatal killing. Although it has been known for a long time that some women deny their pregnancy and may kill their newborns, there is still no consensus on the etiopathogenic factors involved in the denial of pregnancy occurrence. Even though neonaticide is often committed by young, poor, unmarried women with little or no prenatal care, it appears that denial of pregnancy is a heterogeneous condition associated with different psychological features. Societies are ambivalent with regard to mothers who killed their children and tend to lay the entire blame on them. Furthermore, there is a widespread lack of understanding among the public on these affairs, when birth control techniques and methods are widely available. The purpose of this article is to describe the different types of pregnancy denial and neonaticide and to review the still debated etiopathogenic hypotheses. The absence of the physical changes of pregnancy at the time of the denial such as cessation of menstruation, abdominal swelling or perception of foetal movements is also discussed. PMID:22939654

  19. Cortical Lewy body dementia: clinical features and classification.

    PubMed Central

    Gibb, W R; Luthert, P J; Janota, I; Lantos, P L

    1989-01-01

    Seven patients, aged 65-72 years, are described with dementia and cortical Lewy bodies. In one patient a Parkinsonian syndrome was followed by dementia and motor neuron disease. In the remaining six patients dementia was accompanied by dysphasia, dyspraxia and agnosia. One developed a Parkinsonian syndrome before the dementia, in three cases a Parkinsonian syndrome occurred later, and in two cases not at all. All patients showed Lewy bodies and cell loss in the substantia nigra, locus coeruleus and dorsal vagal nucleus, as in Parkinson's disease. The severity of cell loss in the nucleus basalis varied from mild to severe. Lewy bodies were also present in the parahippocampus and cerebral cortex, but Alzheimer-type pathology was mild or absent, and insufficient for a diagnosis of Alzheimer's disease. Patients with moderate or severe dementia, some with temporal or parietal features, may have cortical Lewy body disease, Alzheimer's disease, or a combination of the two. Cortical Lewy body disease may be associated with dementia in Parkinson's disease more often than realised, but is not necessarily associated with extensive Alzheimer pathology. Images PMID:2467966

  20. Genes, Race, and Culture in Clinical Care

    PubMed Central

    Hunt, Linda M.; Truesdell, Nicole D.; Kreiner, Meta J.

    2015-01-01

    Race, although an unscientific concept, remains prominent in health research and clinical guidelines, and is routinely invoked in clinical practice. In interviews with 58 primary care clinicians we explored how they understand and apply concepts of racial difference. We found wide agreement that race is important to consider in clinical care. They explained the effect of race on health, drawing on common assumptions about the biological, class, and cultural characteristics of racial minorities. They identified specific race-based clinical strategies for only a handful of conditions and were inconsistent in the details of what they said should be done for minority patients. We conclude that using race in clinical medicine promotes and maintains the illusion of inherent racial differences and may result in minority patients receiving care aimed at presumed racial group characteristics, rather than care selected as specifically appropriate for them as individuals. [race and genetics, primary care, health disparities, racial profiling] PMID:23804331

  1. Recognizing clinical entities in hospital discharge summaries using Structural Support Vector Machines with word representation features

    PubMed Central

    2013-01-01

    Background Named entity recognition (NER) is an important task in clinical natural language processing (NLP) research. Machine learning (ML) based NER methods have shown good performance in recognizing entities in clinical text. Algorithms and features are two important factors that largely affect the performance of ML-based NER systems. Conditional Random Fields (CRFs), a sequential labelling algorithm, and Support Vector Machines (SVMs), which is based on large margin theory, are two typical machine learning algorithms that have been widely applied to clinical NER tasks. For features, syntactic and semantic information of context words has often been used in clinical NER systems. However, Structural Support Vector Machines (SSVMs), an algorithm that combines the advantages of both CRFs and SVMs, and word representation features, which contain word-level back-off information over large unlabelled corpus by unsupervised algorithms, have not been extensively investigated for clinical text processing. Therefore, the primary goal of this study is to evaluate the use of SSVMs and word representation features in clinical NER tasks. Methods In this study, we developed SSVMs-based NER systems to recognize clinical entities in hospital discharge summaries, using the data set from the concept extration task in the 2010 i2b2 NLP challenge. We compared the performance of CRFs and SSVMs-based NER classifiers with the same feature sets. Furthermore, we extracted two different types of word representation features (clustering-based representation features and distributional representation features) and integrated them with the SSVMs-based clinical NER system. We then reported the performance of SSVM-based NER systems with different types of word representation features. Results and discussion Using the same training (N = 27,837) and test (N = 45,009) sets in the challenge, our evaluation showed that the SSVMs-based NER systems achieved better performance than the CRFs

  2. Emerinopathy and Laminopathy Clinical, pathological and molecular features of muscular dystrophy with nuclear envelopathy in Japan

    PubMed Central

    Astejada, MN; Goto, K; Nagano, A; Ura, S; Noguchi, S; Nonaka, I; Nishino, I; Hayashi, YK

    2007-01-01

    Summary Mutations in the genes for nuclear envelope proteins of emerin (EMD) and lamin A/C (LMNA) are known to cause Emery-Dreifuss muscular dystrophy (EDMD) and limb girdle muscular dystrophy (LGMD). We compared clinical features of the muscular dystrophy patients associated with mutations in EMD (emerinopathy) and LMNA (laminopathy) in our series. The incidence of laminopathy was slightly higher than that of emerinopathy. The age at onset of the disease in emerinopathy was variable and significantly older than in laminopathy. The initial symptom of emerinopathy was also variable, whereas nearly all laminopathy patients presented initially with muscle weakness. Calf hypertrophy was often seen in laminopathy, underscoring the importance of mutation screening for LMNA in childhood muscular dystrophy with calf hypertrophy. The clinical spectrum of emerinopathy is actually wider than previously known including EDMD, LGMD, conduction defects with minimal muscle/joint involvement, and their intermittent forms. Pathologically, no marked difference was observed between emerinopathy and laminopathy. Increased number and variation in size of myonuclei were detected. More precise observations using electron microscopy is warranted to characterize the detailed nuclear changes in nuclear envelopathy. PMID:18646565

  3. Acute chorioamnionitis and funisitis: definition, pathologic features, and clinical significance.

    PubMed

    Kim, Chong Jai; Romero, Roberto; Chaemsaithong, Piya; Chaiyasit, Noppadol; Yoon, Bo Hyun; Kim, Yeon Mee

    2015-10-01

    Acute inflammatory lesions of the placenta consist of diffuse infiltration of neutrophils at different sites in the organ. These lesions include acute chorioamnionitis, funisitis, and chorionic vasculitis and represent a host response (maternal or fetal) to a chemotactic gradient in the amniotic cavity. While acute chorioamnionitis is evidence of a maternal host response, funisitis and chorionic vasculitis represent fetal inflammatory responses. Intraamniotic infection generally has been considered to be the cause of acute chorioamnionitis and funisitis; however, recent evidence indicates that "sterile" intraamniotic inflammation, which occurs in the absence of demonstrable microorganisms induced by "danger signals," is frequently associated with these lesions. In the context of intraamniotic infection, chemokines (such as interleukin-8 and granulocyte chemotactic protein) establish a gradient that favors the migration of neutrophils from the maternal or fetal circulation into the chorioamniotic membranes or umbilical cord, respectively. Danger signals that are released during the course of cellular stress or cell death can also induce the release of neutrophil chemokines. The prevalence of chorioamnionitis is a function of gestational age at birth, and present in 3-5% of term placentas and in 94% of placentas delivered at 21-24 weeks of gestation. The frequency is higher in patients with spontaneous labor, preterm labor, clinical chorioamnionitis (preterm or term), or ruptured membranes. Funisitis and chorionic vasculitis are the hallmarks of the fetal inflammatory response syndrome, a condition characterized by an elevation in the fetal plasma concentration of interleukin-6, and associated with the impending onset of preterm labor, a higher rate of neonatal morbidity (after adjustment for gestational age), and multiorgan fetal involvement. This syndrome is the counterpart of the systemic inflammatory response syndrome in adults: a risk factor for short- and long

  4. Characteristic features of the nucleotide sequences of yeast mitochondrial ribosomal protein genes as analyzed by computer program GeneMark.

    PubMed

    Isono, K; McIninch, J D; Borodovsky, M

    1994-01-01

    The nucleotide sequence data for yeast mitochondrial ribosomal protein (MRP) genes were analyzed by the computer program GeneMark which predicts the presence of likely genes in sequence data by calculating statistical biases in the appearance of consecutive nucleotides. The program uses a set of standard sequence data for this calculation. We used this program for the analysis of yeast nucleotide sequence data containing MRP genes, hoping to obtain information as to whether they share features in common that are different from other yeast genes. Sequence data sets for ordinary yeast genes and for 27 known MRP genes were used. The MRP genes were nicely predicted as likely genes regardless of the data sets used, whereas other yeast genes were predicted to be likely genes only when the data set for ordinary yeast genes was used. The assembled sequence data for chromosomes II, III, VIII and XI as well as the segmented data for chromosome V were analyzed in a similar manner. In addition to the known MRP genes, eleven ORF's were predicted to be likely MRP genes. Thus, the method seems very powerful in analyzing genes of heterologous origins. PMID:7719921

  5. Etiology, clinical features and prognosis in secondary amenorrhea.

    PubMed

    Hirvonen, E

    1977-01-01

    A clinical investigation of 356 patients with secondary amenorrhea revealed that 95% of patients with postpill amenorrhea and 56% of patients with anorexia nervosa recovered in 6 years. The corresponding recovery rates for patients with psychogenic amenorrhea and amenorrhea following self-induced weight loss were 72% for both groups, and in patients with the amenorrhea-galactorrhea syndrome and idiophatic functional amenorrhea the recovery rates at 6 years were 64 and 61% respectively. Unlike the other groups with functional amenorrhea, patients with the amenorrhea-galactorrhea syndrome had impaired ovarian responsiveness to exogenous gonadotropins. Bromocriptine treatment resulted in disappearance of the galactorrhea and restoration of the menses and/or ovulation in nine of 18 patients; of these three became pregnant. The effect of bromocriptine did not persist for long after treatment ceased, and permanent recovery was recorded only in four patients. The group with functional amenorrhea included 34 patients who wished to become pregnant. Gonadotropin treatment was successful in 20 patients, clomiphene-hCG in two, tamoxifen in two, bromocriptine in two, and combined bromocriptine and clomiphene in one. Thus, the overall pregnancy rate in patients with functional amenorrhea was 79%. The groups with ovarian amenorrhea inclutients with assumed ovarian failure responded to large doses of exogenous gonadotropins by ovulation and three became pregnant. Ovarian wedge resection was ineffective in all five cases with polycystic ovaries, but two patients became pregnant after treatment with clomiphene and chorionic gonadotropin, and one with exogenous gonadotropins. PMID:20414

  6. Alternaria infections: laboratory diagnosis and relevant clinical features.

    PubMed

    Pastor, F J; Guarro, J

    2008-08-01

    The genus Alternaria contains several species of melanized hyphomycetes that cause opportunistic human infections. The published literature contains 210 reported cases of human alternarioses between 1933 and the present day. The most frequent clinical manifestations are cutaneous and subcutaneous infections (74.3%), followed by oculomycosis (9.5%), invasive and non-invasive rhinosinusitis (8.1%) and onychomycosis (8.1%). Immunosuppression is frequently associated with cutaneous and subcutaneous infections and rhinosinusitis. The most important risk factors for cutaneous and subcutaneous infections are solid organ transplantation and Cushing's syndrome, and those for rhinosinusitis are bone marrow transplants. Having been exposed to soil and garbage is common in all cases of oculomycosis, with corticotherapy being a risk factor in 50% of these cases. Previous contact with soil and/or trauma to the nails is associated with most cases of onychomycosis. In general, alternariosis shows a good response to conventional antifungal drugs. On some occasions, steroid suppression or reduction is sufficient to resolve an infection. Itraconazole is the antifungal drug used most frequently to successfully treat onychomycosis and cutaneous and subcutaneous infections. Posaconazole and voriconazole are promising therapeutic options, with the latter being especially so for oculomycosis. PMID:18727797

  7. Clinical Features and Treatment of Penile Schwannoma: A Systematic Review.

    PubMed

    Nguyen, Austin Huy; Smith, Megan L; Maranda, Eric L; Punnen, Sanoj

    2016-06-01

    Schwannomas, although common in the head and limbs, are an exceedingly rare tumor of the penis. We conducted a systematic review to include 33 patients with schwannoma of the penile shaft or glans penis. Most patients presented with a single painless nodule on the dorsal aspect of the penile shaft. These nodules were slow growing, with an average of 62 months from the onset to presentation. Several cases were accompanied by sexual dysfunction. Most histologic studies were consistent, with a benign schwannoma that showed a palisading Antoni A and Antoni B pattern without malignant changes in cell morphology. Of the 14 studies in which a history of genetic disease was investigated, only 2 reported a connection to neurofibromatosis. These tumors were treated with surgical excision, and 4 malignant cases received additional chemotherapy or radiotherapy. All the patients had achieved full remission by the final follow-up examination. Given the rarity of this tumor, the present review of available case studies serves to comprehensively describe the clinical presentation and treatment approaches to penile schwannoma. PMID:26797586

  8. Actinomycosis: etiology, clinical features, diagnosis, treatment, and management

    PubMed Central

    Valour, Florent; Sénéchal, Agathe; Dupieux, Céline; Karsenty, Judith; Lustig, Sébastien; Breton, Pierre; Gleizal, Arnaud; Boussel, Loïc; Laurent, Frédéric; Braun, Evelyne; Chidiac, Christian; Ader, Florence; Ferry, Tristan

    2014-01-01

    Actinomycosis is a rare chronic disease caused by Actinomyces spp., anaerobic Gram-positive bacteria that normally colonize the human mouth and digestive and genital tracts. Physicians must be aware of typical clinical presentations (such as cervicofacial actinomycosis following dental focus of infection, pelvic actinomycosis in women with an intrauterine device, and pulmonary actinomycosis in smokers with poor dental hygiene), but also that actinomycosis may mimic the malignancy process in various anatomical sites. Bacterial cultures and pathology are the cornerstone of diagnosis, but particular conditions are required in order to get the correct diagnosis. Prolonged bacterial cultures in anaerobic conditions are necessary to identify the bacterium and typical microscopic findings include necrosis with yellowish sulfur granules and filamentous Gram-positive fungal-like pathogens. Patients with actinomycosis require prolonged (6- to 12-month) high doses (to facilitate the drug penetration in abscess and in infected tissues) of penicillin G or amoxicillin, but the duration of antimicrobial therapy could probably be shortened to 3 months in patients in whom optimal surgical resection of infected tissues has been performed. Preventive measures, such as reduction of alcohol abuse and improvement of dental hygiene, may limit occurrence of pulmonary, cervicofacial, and central nervous system actinomycosis. In women, intrauterine devices must be changed every 5 years in order to limit the occurrence of pelvic actinomycosis. PMID:25045274

  9. Clinical Features of Oxaliplatin Induced Hypersensitivity Reactions and Therapeutic Approaches.

    PubMed

    Bano, Nusrat; Najam, Rahila; Qazi, Faaiza; Mateen, Ahmed

    2016-01-01

    Oxaliplatin, a third generation novel platinum compound is the most effective first line chemotherapeutic agent for colorectal cancer (CRC) in combination with 5FU and leucovorin. It is indicated for pancreatic, gastric and testicular cancers combined with bevacuzimab, capecitabine, irinotecan and other cytotoxic agents. However, moderate to severe hypersensitivity reactions (HSR) during or after oxaliplatin infusion usually require cessation of chemotherapy or substitution of the key therapeutic drug which largely interferes with improved patient prognosis. This mini- review showcases recent and accepted opinions/approaches in oxaliplatin induced HSR management. Physicians and oncologists have varying attitudes regarding the decision to rechallenge the patient after an HSR experience, efficacy of desensitization protocols, effectiveness and selection of drugs for premedication and possibilities of cross sensitivity to other platinum agents (e.g. carboplatin). A brief insight into underlying molecular mechanisms and clinical manifestations of oxaliplatin induced HSR is offered. We have also discussed the management of oxaliplatin induced HSR and risk stratification for a successful and complete chemotherapeutic plan. PMID:27221832

  10. Clinical and laboratory features of human herpesvirus 6 chromosomal integration.

    PubMed

    Clark, D A

    2016-04-01

    Human herpesvirus 6 (HHV-6) comprises two separate viruses, HHV-6A and HHV-6B, although this distinction is not commonly made. HHV-6B is ubiquitous in the population with primary infection usually occurring in early childhood, and often resulting in febrile illness. HHV-6B is also recognized as a pathogen in the immunocompromised host, particularly in transplant recipients. HHV-6A is less well characterized and may have a more restricted prevalence. Both viruses are unique among the human herpesviruses in that the entire viral genome can be found integrated into the telomeric regions of host cell chromosomes. Approximately 1% of persons have inherited integrated viral sequences through the germline, and these individuals characteristically have very high viral loads in blood and other sample types. Emerging evidence suggests that HHV-6A and HHV-6B chromosomal integration may not just be an uncommon biological observation, but more likely a characteristic of the replication properties of these viruses. The integrated viral genome appears capable of excision from the chromosomal site and potentially allows viral replication. The clinical consequences of inherited chromosomally integrated HHV-6 have yet to be fully appreciated. PMID:26802216

  11. Metabolic brain imaging correlated with clinical features of brain tumors

    SciTech Connect

    Alavi, J.; Alavi, A.; Dann, R.; Kushner, M.; Chawluk, J.; Powlis, W.; Reivich, M.

    1985-05-01

    Nineteen adults with brain tumors have been studied with positron emission tomography utilizing FDG. Fourteen had biopsy proven cerebral malignant glioma, one each had meningioma, hemangiopericytoma, primitive neuroectodermal tumor (PNET), two had unbiopsied lesions, and one patient had an area of biopsy proven radiation necrosis. Three different patterns of glucose metabolism are observed: marked increase in metabolism at the site of the known tumor in (10 high grade gliomas and the PNET), lower than normal metabolism at the tumor (in 1 grade II glioma, 3 grade III gliomas, 2 unbiopsied low density nonenhancing lesions, and the meningioma), no abnormality (1 enhancing glioma, the hemangiopericytoma and the radiation necrosis.) The metabolic rate of the tumor or the surrounding brain did not appear to be correlated with the history of previous irradiation or chemotherapy. Decreased metabolism was frequently observed in the rest of the affected hemisphere and in the contralateral cerebellum. Tumors of high grade or with enhancing CT characteristics were more likely to show increased metabolism. Among the patients with proven gliomas, survival after PETT scan tended to be longer for those with low metabolic activity tumors than for those with highly active tumors. The authors conclude that PETT may help to predict the malignant potential of tumors, and may add useful clinical information to the CT scan.

  12. [Vasculitic Peripheral Neuropathies: Clinical Features and Diagnostic Laboratory Tests].

    PubMed

    Ogata, Katsuhisa

    2016-03-01

    Vasculitic peripheral neuropathy (VPN) occurs due to ischemic changes of peripheral nerves, resulting from a deficit of vascular blood supply due to damaged vasa nervorum leading to vasculitis. VPN usually manifests as sensorimotor or sensory disturbances accompanied by pain, presenting as a type of multiple mononeuropathy, with a scattered distribution in distal limbs. VPN may also present as a mononeuropathy, distal symmetric polyneuropathy, plexopathy, or radiculopathy. The rapidity of VPN is variable, ranging from days to months, with symptoms occasionally changing with the appearance of new lesions. Careful history taking and neurological examination provides an exact diagnosis. The most common cause of VPN is primary vasculitis predominantly affecting small vessels, including vasa nervorum, anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis, and polyarteritis nodosa. Similar vasculitic processes can also result from a systemic collagen disorder or secondary vasculitis. Electrophysiological studies and pathological investigation of biopsied peripheral nerves and muscles are important for diagnosis of vasculitis. Serological tests, including ANCA, are useful for diagnosis of vasculitis. Accurate neurological examinations are essential for diagnosis and evaluation of clinical course. PMID:27001769

  13. Clinical, histopathologic & immunologic features of cutaneous lesions in acute meningococcaemia.

    PubMed

    Ramesh, V; Mukherjee, A; Chandra, M; Sehgal, S K; Saxena, U; Jain, A K; Wadhwa, A

    1990-01-01

    Fifty children with culture proven acute meningococcaemia were studied during the winter outbreak of the disease in 1986-87. Purpuric lesions were seen in 60 per cent, erythematous papules in 32 per cent, faint pink macules in 28 per cent, conjunctival petechiae in 10 per cent and herpes labialis in 20 per cent. Histopathology of skin lesions showed that the primary damage was to the dermal vessels, the extent of damage depending on the type of skin involvement. Diplococci in Gram's stained sections were seen frequently in purpuric as compared to the other skin lesions. They were located in degenerating neutrophils, endothelial cells, fibrin clots or freely in the vascular lumen. Electron microscopic study showed vascular changes accompanied by a perivascular phagocytic response. Both light and electronmicroscopy indicated the involvement of the coagulative mechanism in the pathogenesis of meningococcaemia. However, clinical parameters of clotting were often within normal limits. In the case of a child (who died eventually), a low platelet count and prolonged coagulation indices were observed. Sera from some of the children were tested for the presence of antibodies against meningococci by indirect immunofluorescence. Antibodies were detected in the sera and they may have a role in regulating the severity and course of the illness. The significance of immunoglobulin deposits in the skin lesions is not clear. PMID:2111800

  14. Correlations of clinical, neuroimaging, and electrophysiological features in Hirayama disease

    PubMed Central

    Liao, Ming-Feng; Chang, Hong-Shiu; Chang, Kuo-Hsuan; Ro, Long-Sun; Chu, Chun-Che; Kuo, Hung-Chou; Lyu, Rong-Kuo

    2016-01-01

    Abstract Hirayama disease (HD) is characterized by development of asymmetric forearm muscle atrophy during adolescence with or without focal cervical spinal cord atrophy. The purpose of this study is to assess the correlation of clinical symptoms, disease progression, and electrophysiological findings with cervical spine magnetic resonance imaging (MRI) findings. The medical records, cervical spine MRIs, and electrophysiological findings of 44 HD patients were retrospectively reviewed and analyzed. Denervation changes in any single C5 to C7 root-innervated muscle (deltoid, biceps, triceps, or extensor digitorum communis) occurred more frequently in the 25 patients with cord atrophy than the 19 patients without cord atrophy (88% vs 53%, P = 0.02). Onset age, duration of disease progression, neurological examinations, nerve conduction study, and electromyographic findings from individual muscles were similar between patient groups. Compared with HD patients without cord atrophy, HD patients with cord atrophy experience a more severe denervation change in C5 to C7 root-innervated muscles. PMID:27428223

  15. Viral Vectors for Gene Therapy: Current State and Clinical Perspectives.

    PubMed

    Lukashev, A N; Zamyatnin, A A

    2016-07-01

    Gene therapy is the straightforward approach for the application of recent advances in molecular biology into clinical practice. One of the major obstacles in the development of gene therapy is the delivery of the effector to and into the target cell. Unfortunately, most methods commonly used in laboratory practice are poorly suited for clinical use. Viral vectors are one of the most promising methods for gene therapy delivery. Millions of years of evolution of viruses have resulted in the development of various molecular mechanisms for entry into cells, long-term survival within cells, and activation, inhibition, or modification of the host defense mechanisms at all levels. The relatively simple organization of viruses, small genome size, and evolutionary plasticity allow modifying them to create effective instruments for gene therapy approaches. This review summarizes the latest trends in the development of gene therapy, in particular, various aspects and prospects of the development of clinical products based on viral delivery systems. PMID:27449616

  16. Clinical utility of a next generation sequencing panel assay for Marfan and Marfan-like syndromes featuring aortopathy.

    PubMed

    Wooderchak-Donahue, Whitney; VanSant-Webb, Chad; Tvrdik, Tatiana; Plant, Parker; Lewis, Tracey; Stocks, Jennifer; Raney, Joshua A; Meyers, Lindsay; Berg, Alizabeth; Rope, Alan F; Yetman, Anji T; Bleyl, Steven B; Mesley, Rebecca; Bull, David A; Collins, R Thomas; Ojeda, Mayra Martinez; Roberts, Amy; Lacro, Ronald; Woerner, Audrey; Stoler, Joan; Bayrak-Toydemir, Pinar

    2015-08-01

    Aortopathy can be defined as aortic dilation, aneurysm, dissection, and tortuosity. Familial aortopathy may occur secondary to fibrillin-1 (FBN1) mutations in the setting of Marfan syndrome, or may occur as a result of other genetic defects with different, but occasionally overlapping, phenotypes. Because of the phenotypic overlap and genetic heterogeneity of disorders featuring aortopathy, we developed a next generation sequencing (NGS) assay and comparative genomic hybridization (CGH) array to detect mutations in 10 genes that cause thoracic aortic aneurysms (TAAs). Here, we report on the clinical and molecular findings in 175 individuals submitted for aortopathy panel testing at ARUP laboratories. Ten genes associated with heritable aortopathies were targeted using hybridization capture prior to sequencing. NGS results were analyzed, and variants were confirmed using Sanger sequencing. Array CGH was used to detect copy-number variation. Of 175 individuals, 18 had a pathogenic mutation and 32 had a variant of uncertain significance (VUS). Most pathogenic mutations (72%) were identified in FBN1. A novel large SMAD3 duplication and FBN1 deletion were identified. Over half who had TAAs or other aortic involvement tested negative for a mutation, suggesting that additional aortopathy genes exist. We anticipate that the clinical sensitivity of at least 10.3% will rise with VUS reclassification and as additional genes are identified and included in the panel. The aortopathy NGS panel aids in the timely molecular diagnosis of individuals with disorders featuring aortopathy and guides proper treatment. PMID:25944730

  17. Splenic abscess: clinical features, microbiologic finding, treatment and outcome.

    PubMed

    Sangchan, Apichat; Mootsikapun, Piroon; Mairiang, Pisaln

    2003-05-01

    Splenic abscess is a rare clinical entity but may be underreported. A retrospective study at Srinagarind Hospital revealed 60 cases of splenic abscess between 1992 and 2001. The causative organisms were identified in 41 cases (68.3%). Gram negative bacilli were commonly isolated and Burkholderia pseudomallei was the most predominant. Diabetes mellitus and leukemia were common underlying diseases found in 46.3 per cent and 9.7 per cent of culture confirmed cases, respectively. The patients usually presented with fever, left upper quadrant pain, tenderness and splenomegaly. Multiple abscesses were more commonly found in the melioidosis than in the non-melioidosis group (p = 0.032), but a single abscess was more commonly found in the non-melioidosis than in the melioidosis group (p = 0.032). Concurrent liver abscesses, often multiple, were not different in both groups. Antimicrobials alone were given in 66.7 per cent of cases with melioidosis and 64.7 per cent of non-melioidosis group. Splenectomy and percutaneous aspiration were performed only in 29.3 per cent and 4.9 per cent of cases with splenic abscess. The overall mortality rate of splenic abscess was only 4.9 per cent in the present series. In conclusion, splenic abscess is not uncommon. Burkholderia pseudomalleli is the most common causative agent found in the present series. Therefore, it should be targeted in the initial empirical antibiotic therapy before the culture results are available especially when multiple lesions in the spleen and concurrent multiple liver abscesses are seen. Prolonged treatment with appropriate antimicrobials alone is usually effective. Splenectomy and/or aspiration may be useful in selected patients. PMID:12859100

  18. Clinical Distinct Features of Noncardiac Chest Pain in Young Patients

    PubMed Central

    Seo, Tae Ho; Lee, Jung Hyeon; Ko, Soon Young; Hong, Sung Noh; Sung, In-Kyung; Park, Hyung Seok; Shim, Chan Sub

    2010-01-01

    Background/Aims Noncardiac chest pain (NCCP) is a very common disorder world-wide and gastroesophageal reflux disease (GERD) is known to be the most common cause. The prevalence of NCCP may tend to decrease with increasing age. However, there is little report about young aged NCCP. The aim of this study was to examine the prevalence of GERD and to evaluate the efficacy of proton pump inhibitor (PPI) test in the young NCCP patients. Methods Thirty patients with at least weekly NCCP less than 40 years were enrolled. The baseline symptoms were assessed using a daily symptom diary for 14 days. Esophago-gastro-duodenoscopy (EGD) and 24 hr esophageal pH monitoring were performed for the diagnosis of GERD and esophageal manometry was done. Then, patients were tried with lansoprazole 30 mg twice daily for 14 days, considering positive if a symptom score improved ≥ 50% compared to the baseline. Results Nine (30%) of the patients were diagnosed with GERD at EGD and/or 24 hr esophageal pH monitoring, also, 3 (10%) were diagnosed with GERD-associated esophageal motility disorder and 3 (10%) were non GERD-associated. Concerning PPI test, GERD-related NCCP had a higher positive PPI test (n = 8, 89%) than non GERD-related NCCP (n = 5, 24%) (p = 0.002). Conclusions In young patients with NCCP, a prevalence of GERD diagnosed using EGD and/or 24 hr esophageal pH monitoring was 30%. PPI test was very predictable on diagnosis of GERD-related NCCP, thus, PPI test in young NCCP patients may assist to the physician's clinical judgment of NCCP. PMID:20535347

  19. Acute Acquired Concomitant Esotropia: Clinical features, Classification, and Etiology.

    PubMed

    Chen, Jingchang; Deng, Daming; Sun, Yuan; Shen, Tao; Cao, Guobin; Yan, Jianhua; Chen, Qiwen; Ye, Xuelian

    2015-12-01

    Acute acquired concomitant esotropia (AACE) is a rare, distinct subtype of esotropia. The purpose of this retrospective study was to describe the clinical characteristics and discuss the classification and etiology of AACE.Charts from 47 patients with AACE referred to our institute between October 2010 and November 2014 were reviewed. All participants underwent a complete medical history, ophthalmologic and orthoptic examinations, and brain and orbital imaging.Mean age at onset was 26.6 ± 12.2 years. Of the 18 cases with deviations ≤ 20 PD, 16 presented with diplopia at distance and fusion at near vision at the onset of deviation; differences between distance and near deviations were < 8 PD; all cases except one were treated with prism and diplopia resolved. Of the 29 cases with deviations > 20 PD, 5 were mild hypermetropic with age at onset between 5 and 19 years, 16 were myopic, and 8 were emmetropic with age at onset > 12 years; 24 were surgically treated and 5 cases remained under observation; all 24 cases achieved normal retinal correspondence or fusion or stereopsis on postoperative day 1 in synoptophore; in 23 cases diplopia or visual confusion resolved postoperatively. Of the 47 cases, brain and orbital imaging in 2 cases revealed a tumor in the cerebellopontine angle and 1 case involved spinocerebellar ataxia as revealed by genetic testing.AACE in this study was characterized by a sudden onset of concomitant nonaccommodative esotropia with diplopia or visual confusion at 5 years of age or older and the potential for normal binocular vision. We suggest that AACE can be divided into 2 subgroups consisting of patients with relatively small versus large angle deviations. Coexisting or underlying neurological diseases were infrequent in AACE. PMID:26705210

  20. Gene Therapy in Cardiac Surgery: Clinical Trials, Challenges, and Perspectives

    PubMed Central

    Katz, Michael G.; Fargnoli, Anthony S.; Kendle, Andrew P.; Hajjar, Roger J.; Bridges, Charles R.

    2016-01-01

    The concept of gene therapy was introduced in the 1970s after the development of recombinant DNA technology. Despite the initial great expectations, this field experienced early setbacks. Recent years have seen a revival of clinical programs of gene therapy in different fields of medicine. There are many promising targets for genetic therapy as an adjunct to cardiac surgery. The first positive long-term results were published for adenoviral administration of vascular endothelial growth factor with coronary artery bypass grafting. In this review we analyze the past, present, and future of gene therapy in cardiac surgery. The articles discussed were collected through PubMed and from author experience. The clinical trials referenced were found through the Wiley clinical trial database (http://www.wiley.com/legacy/wileychi/genmed/clinical/) as well as the National Institutes of Health clinical trial database (Clinicaltrials.gov). PMID:26801060

  1. Gene Therapy in Cardiac Surgery: Clinical Trials, Challenges, and Perspectives.

    PubMed

    Katz, Michael G; Fargnoli, Anthony S; Kendle, Andrew P; Hajjar, Roger J; Bridges, Charles R

    2016-06-01

    The concept of gene therapy was introduced in the 1970s after the development of recombinant DNA technology. Despite the initial great expectations, this field experienced early setbacks. Recent years have seen a revival of clinical programs of gene therapy in different fields of medicine. There are many promising targets for genetic therapy as an adjunct to cardiac surgery. The first positive long-term results were published for adenoviral administration of vascular endothelial growth factor with coronary artery bypass grafting. In this review we analyze the past, present, and future of gene therapy in cardiac surgery. The articles discussed were collected through PubMed and from author experience. The clinical trials referenced were found through the Wiley clinical trial database (http://www.wiley.com/legacy/wileychi/genmed/clinical/) as well as the National Institutes of Health clinical trial database (Clinicaltrials.gov). PMID:26801060

  2. New Molecular Features of Colorectal Cancer Identified - Office of Cancer Clinical Proteomics Research

    Cancer.gov

    Investigators from the National Cancer Institute's Clinical Proteomic Tumor Analysis Consortium (CPTAC) who comprehensively analyzed 95 human colorectal tumor samples, have determined how gene alterations identified in previous analyses of the same samples

  3. Copy number polymorphisms are not a common feature of innate immune genes.

    PubMed

    Linzmeier, Rose M; Ganz, Tomas

    2006-07-01

    Extensive copy number polymorphism was recently reported for innate immunity-related alpha-defensin genes DEFA1 and DEFA3 and beta-defensin genes DEFB4, DEFB103, and DEFB104. To establish whether such polymorphisms are a common feature of innate immune genes we used quantitative real-time PCR to determine the copy numbers of seven genes whose products have important innate immune functions. The genes encoding lysozyme, lactoferrin, cathelicidin antimicrobial peptide (hCAP18/LL-37), cathepsin G, bactericidal/permeability-increasing protein, azurocidin (CAP37/heparin-binding protein), and neutrophil elastase were each found to be single copy per haploid genome. These findings, along with the recent observation that defensin genes DEFA4, DEFA5, DEFA6, and DEFB1 are single copy, suggest that copy number polymorphisms are not a common feature of the innate immune genome but are restricted to a small subset of innate immunity-related genes. PMID:16617005

  4. Four New Families with Autosomal Dominant Partial Epilepsy with Auditory Features: Clinical Description and Linkage to Chromosome 10q24

    PubMed Central

    Winawer, Melodie R.; Boneschi, Filippo Martinelli; Barker-Cummings, Christie; Lee, Joseph H.; Liu, Jianjun; Mekios, Constantine; Gilliam, T. Conrad; Pedley, Timothy A.; Hauser, W. Allen; Ottman, Ruth

    2009-01-01

    Summary Purpose Autosomal dominant partial epilepsy with auditory features (ADPEAF) is a rare form of nonprogressive lateral temporal lobe epilepsy characterized by partial seizures with auditory disturbances. The gene predisposing to this syndrome was localized to a 10-cM region on chromosome 10q24. We assessed clinical features and linkage evidence in four newly ascertained families with ADPEAF, to refine the clinical phenotype and confirm the genetic localization. Methods We genotyped 41 individuals at seven microsatellite markers spanning the previously defined 10-cM minimal genetic region. We conducted two-point linkage analysis with the ANALYZE computer package, and multipoint parametric and nonparametric linkage analyses as implemented in GENEHUNTER2. Results In the four families, the number of individuals with idiopathic epilepsy ranged from three to nine. Epilepsy was focal in all of those with idiopathic epilepsy who could be classified. The proportion with auditory symptoms ranged from 67 to 100%. Other ictal symptoms also were reported; of these, sensory symptoms were most common. Linkage analysis showed a maximum 2-point LOD score of 1.86 at (θ = 0.0 for marker D10S603, and a maximum multipoint LOD score of 2.93. Conclusions These findings provide strong confirmation of linkage of a gene causing ADPEAF to chromosome 10q24. The results suggest that the susceptibility gene has a differential effect on the lateral temporal lobe, thereby producing the characteristic clinical features described here. Molecular studies aimed at the identification of the causative gene are underway. PMID:11879388

  5. Integrative topological analysis of mass spectrometry data reveals molecular features with clinical relevance in esophageal squamous cell carcinoma.

    PubMed

    Gao, She-Gan; Liu, Rui-Min; Zhao, Yun-Gang; Wang, Pei; Ward, Douglas G; Wang, Guang-Chao; Guo, Xiang-Qian; Gu, Juan; Niu, Wan-Bin; Zhang, Tian; Martin, Ashley; Guo, Zhi-Peng; Feng, Xiao-Shan; Qi, Yi-Jun; Ma, Yuan-Fang

    2016-01-01

    Combining MS-based proteomic data with network and topological features of such network would identify more clinically relevant molecules and meaningfully expand the repertoire of proteins derived from MS analysis. The integrative topological indexes representing 95.96% information of seven individual topological measures of node proteins were calculated within a protein-protein interaction (PPI) network, built using 244 differentially expressed proteins (DEPs) identified by iTRAQ 2D-LC-MS/MS. Compared with DEPs, differentially expressed genes (DEGs) and comprehensive features (CFs), structurally dominant nodes (SDNs) based on integrative topological index distribution produced comparable classification performance in three different clinical settings using five independent gene expression data sets. The signature molecules of SDN-based classifier for distinction of early from late clinical TNM stages were enriched in biological traits of protein synthesis, intracellular localization and ribosome biogenesis, which suggests that ribosome biogenesis represents a promising therapeutic target for treating ESCC. In addition, ITGB1 expression selected exclusively by integrative topological measures correlated with clinical stages and prognosis, which was further validated with two independent cohorts of ESCC samples. Thus the integrative topological analysis of PPI networks proposed in this study provides an alternative approach to identify potential biomarkers and therapeutic targets from MS/MS data with functional insights in ESCC. PMID:26898710

  6. Integrative topological analysis of mass spectrometry data reveals molecular features with clinical relevance in esophageal squamous cell carcinoma

    PubMed Central

    Gao, She-Gan; Liu, Rui-Min; Zhao, Yun-Gang; Wang, Pei; Ward, Douglas G.; Wang, Guang-Chao; Guo, Xiang-Qian; Gu, Juan; Niu, Wan-Bin; Zhang, Tian; Martin, Ashley; Guo, Zhi-Peng; Feng, Xiao-Shan; Qi, Yi-Jun; Ma, Yuan-Fang

    2016-01-01

    Combining MS-based proteomic data with network and topological features of such network would identify more clinically relevant molecules and meaningfully expand the repertoire of proteins derived from MS analysis. The integrative topological indexes representing 95.96% information of seven individual topological measures of node proteins were calculated within a protein-protein interaction (PPI) network, built using 244 differentially expressed proteins (DEPs) identified by iTRAQ 2D-LC-MS/MS. Compared with DEPs, differentially expressed genes (DEGs) and comprehensive features (CFs), structurally dominant nodes (SDNs) based on integrative topological index distribution produced comparable classification performance in three different clinical settings using five independent gene expression data sets. The signature molecules of SDN-based classifier for distinction of early from late clinical TNM stages were enriched in biological traits of protein synthesis, intracellular localization and ribosome biogenesis, which suggests that ribosome biogenesis represents a promising therapeutic target for treating ESCC. In addition, ITGB1 expression selected exclusively by integrative topological measures correlated with clinical stages and prognosis, which was further validated with two independent cohorts of ESCC samples. Thus the integrative topological analysis of PPI networks proposed in this study provides an alternative approach to identify potential biomarkers and therapeutic targets from MS/MS data with functional insights in ESCC. PMID:26898710

  7. Clinical and serological features of patients with dermatomyositis complicated by spontaneous pneumomediastinum.

    PubMed

    Ma, Xiaolei; Chen, Zhiyong; Hu, Wei; Guo, Ziwei; Wang, Yan; Kuwana, Masataka; Sun, Lingyun

    2016-02-01

    The purpose of this study was to explore the clinical and serological features of patients with pneumomediastinum (PNM) and dermatomyositis-associated interstitial lung disease (DM-ILD). A total of 93 patients (68 with classic DM and 25 with clinically amyopathic DM [CADM]) were recruited. Clinical and laboratory data were collected retrospectively. Anti-melanoma differentiation-associated gene 5 (MDA5) antibodies were detected using enzyme-linked immunosorbent assay (ELISA). Variables were compared between patients with and those without PNM. Multivariate analysis was performed using a multivariate logistic regression model. A total of 11 patients developed spontaneous PNM. During the follow-up period, 6 patients died of respiratory failure. No differences in sex, age at the onset of DM, serum ferritin levels, and C-reactive protein (CRP) levels were observed between DM patients with and without PNM. Compared with DM patients without PNM, those with PNM had significantly higher frequencies of rapidly progressive ILD (RP-ILD) (63.6 vs 24.4 %, P = 0.01), anti-MDA5 antibodies (90.9 vs 52.4 %, P = 0.02), CADM diagnoses (63.6 vs 22.0 %, P = 0.007) and cutaneous ulcers (36.4 vs 11 %, P = 0.04), but significantly lower creatine kinase (CK) levels (58.5 vs 284 U/l, P = 0.04). The multivariate analysis indicated that cutaneous ulcer was the only independent risk factor for the occurrence of PNM in DM (OR = 5.98, 95 % confidence interval [CI] 1.12-31.98, P = 0.037). PNM is a refractory complication and tends to occur in DM patients with RP-ILD, anti-MDA5 antibody, CADM diagnosis, and low CK level, and especially in patients with cutaneous ulcers. PMID:26149923

  8. Specific Gene Loci of Clinical Pseudomonas putida Isolates

    PubMed Central

    Molina, Lázaro; Udaondo, Zulema; Duque, Estrella; Fernández, Matilde; Bernal, Patricia; Roca, Amalia; de la Torre, Jesús; Ramos, Juan Luis

    2016-01-01

    Pseudomonas putida are ubiquitous inhabitants of soils and clinical isolates of this species have been seldom described. Clinical isolates show significant variability in their ability to cause damage to hosts because some of them are able to modulate the host’s immune response. In the current study, comparisons between the genomes of different clinical and environmental strains of P. putida were done to identify genetic clusters shared by clinical isolates that are not present in environmental isolates. We show that in clinical strains specific genes are mostly present on transposons, and that this set of genes exhibit high identity with genes found in pathogens and opportunistic pathogens. The set of genes prevalent in P. putida clinical isolates, and absent in environmental isolates, are related with survival under oxidative stress conditions, resistance against biocides, amino acid metabolism and toxin/antitoxin (TA) systems. This set of functions have influence in colonization and survival within human tissues, since they avoid host immune response or enhance stress resistance. An in depth bioinformatic analysis was also carried out to identify genetic clusters that are exclusive to each of the clinical isolates and that correlate with phenotypical differences between them, a secretion system type III-like was found in one of these clinical strains, a determinant of pathogenicity in Gram-negative bacteria. PMID:26820467

  9. Specific gene hypomethylation and cancer: New insights into coding region feature trends

    PubMed Central

    Daura-Oller, Elias; Cabre, Maria; Montero, Miguel A; Paternain, Jose L; Romeu, Antoni

    2009-01-01

    Giving coding region structural features a role in the hypomethylation of specific genes, the occurrence of G+C content, CpG islands, repeat and retrotransposable elements in demethylated genes related to cancer has been evaluated. A comparative analysis among different cancer types has also been performed. In this work, the inter-cancer coding region features comparative analysis carried out, show insights into what structural trends/patterns are present in the studied cancers. PMID:19707296

  10. Clinical-Epidemiological Features of 13 Cases of Melioidosis in Brazil

    PubMed Central

    Bandeira, Tereza J. P. G.; Cordeiro, Rossana A.; Grangeiro, Thalles B.; Lima, Rita A. C.; Ribeiro, Joyce F.; Castelo-Branco, Débora S. C. M.; Rodrigues, Jorge L. N.; Coelho, Ivo C. B.; Magalhães, Francisco G.; Rocha, Marcos F. G.; Sidrim, José J. C.

    2012-01-01

    The aim of this work was to catalog the clinical and ecoepidemiological characteristics of melioidosis in Brazil. The clinical-epidemiological features of melioidosis in Ceará are similar to those in other regions where the disease is endemic. These findings support the inclusion of this Brazilian state as part of the zone of endemicity for melioidosis. PMID:22814457

  11. Fluent Versus Nonfluent Primary Progressive Aphasia: A Comparison of Clinical and Functional Neuroimaging Features

    ERIC Educational Resources Information Center

    Clark, D.G.; Charuvastra, A.; Miller, B.L.; Shapira, J.S.; Mendez, M.F.

    2005-01-01

    To better characterize fluent and nonfluent variants of primary progressive aphasia (PPA). Although investigators have recognized both fluent and nonfluent patients with PPA (Mesulam, 2001), the clinical and neuroimaging features of these variants have not been fully defined. We present clinical and neuropsychological data on 47 PPA patients…

  12. Dynamic features of gene expression control by small regulatory RNAs.

    PubMed

    Mitarai, Namiko; Benjamin, Julie-Anna M; Krishna, Sandeep; Semsey, Szabolcs; Csiszovszki, Zsolt; Massé, Eric; Sneppen, Kim

    2009-06-30

    Small regulatory RNAs (sRNAs) in eukaryotes and bacteria play an important role in the regulation of gene expression either by binding to regulatory proteins or directly to target mRNAs. Two of the best-characterized bacterial sRNAs, Spot42 and RyhB, form a complementary pair with the ribosome binding region of their target mRNAs, thereby inhibiting translation or promoting mRNA degradation. To investigate the steady-state and dynamic potential of such sRNAs, we examine the 2 key parameters characterizing sRNA regulation: the capacity to overexpress the sRNA relative to its target mRNA and the speed at which the target mRNA is irreversibly inactivated. We demonstrate different methods to determine these 2 key parameters, for Spot42 and RyhB, which combine biochemical and genetic experiments with computational analysis. We have developed a mathematical model that describes the functional properties of sRNAs with various characteristic parameters. We observed that Spot42 and RyhB function in distinctive parameter regimes, which result in divergent mechanisms. PMID:19541626

  13. A P-Norm Robust Feature Extraction Method for Identifying Differentially Expressed Genes.

    PubMed

    Liu, Jian; Liu, Jin-Xing; Gao, Ying-Lian; Kong, Xiang-Zhen; Wang, Xue-Song; Wang, Dong

    2015-01-01

    In current molecular biology, it becomes more and more important to identify differentially expressed genes closely correlated with a key biological process from gene expression data. In this paper, based on the Schatten p-norm and Lp-norm, a novel p-norm robust feature extraction method is proposed to identify the differentially expressed genes. In our method, the Schatten p-norm is used as the regularization function to obtain a low-rank matrix and the Lp-norm is taken as the error function to improve the robustness to outliers in the gene expression data. The results on simulation data show that our method can obtain higher identification accuracies than the competitive methods. Numerous experiments on real gene expression data sets demonstrate that our method can identify more differentially expressed genes than the others. Moreover, we confirmed that the identified genes are closely correlated with the corresponding gene expression data. PMID:26201006

  14. Clinical Approach to Parkinson's Disease: Features, Diagnosis, and Principles of Management

    PubMed Central

    Massano, João; Bhatia, Kailash P.

    2012-01-01

    Parkinson's disease (PD) is one of the most common neurodegenerative disorders. The condition causes a heavy burden both on those affected, as well as their families. Accurate diagnosis is critical and remains founded on clinical grounds as no specific diagnostic test is available so far. The clinical picture of PD is typical in many instances; however, features distinguishing it from other disorders should be thoroughly sought. Monogenic forms of PD also have some distinctive characteristics in many cases. This text is a roadmap to accurate diagnosis in PD, as it approaches clinical features, diagnostic methodology, and leading differential diagnoses. Therapeutic issues are also briefly discussed. PMID:22675666

  15. NMFBFS: A NMF-Based Feature Selection Method in Identifying Pivotal Clinical Symptoms of Hepatocellular Carcinoma

    PubMed Central

    Ji, Zhiwei; Meng, Guanmin; Huang, Deshuang; Yue, Xiaoqiang; Wang, Bing

    2015-01-01

    Background. Hepatocellular carcinoma (HCC) is a highly aggressive malignancy. Traditional Chinese Medicine (TCM), with the characteristics of syndrome differentiation, plays an important role in the comprehensive treatment of HCC. This study aims to develop a nonnegative matrix factorization- (NMF-) based feature selection approach (NMFBFS) to identify potential clinical symptoms for HCC patient stratification. Methods. The NMFBFS approach consisted of three major steps. Firstly, statistics-based preliminary feature screening was designed to detect and remove irrelevant symptoms. Secondly, NMF was employed to infer redundant symptoms. Based on NMF-derived basis matrix, we defined a novel similarity measurement of intersymptoms. Finally, we converted each group of redundant symptoms to a new single feature so that the dimension was further reduced. Results. Based on a clinical dataset consisting of 407 patient samples of HCC with 57 symptoms, NMFBFS approach detected 8 irrelevant symptoms and then identified 16 redundant symptoms within 6 groups. Finally, an optimal feature subset with 39 clinical features was generated after compressing the redundant symptoms by groups. The validation of classification performance shows that these 39 features obviously improve the prediction accuracy of HCC patients. Conclusions. Compared with other methods, NMFBFS has obvious advantages in identifying important clinical features of HCC. PMID:26579207

  16. Detection and Classification of Cancer from Microscopic Biopsy Images Using Clinically Significant and Biologically Interpretable Features

    PubMed Central

    Kumar, Rajesh; Srivastava, Subodh

    2015-01-01

    A framework for automated detection and classification of cancer from microscopic biopsy images using clinically significant and biologically interpretable features is proposed and examined. The various stages involved in the proposed methodology include enhancement of microscopic images, segmentation of background cells, features extraction, and finally the classification. An appropriate and efficient method is employed in each of the design steps of the proposed framework after making a comparative analysis of commonly used method in each category. For highlighting the details of the tissue and structures, the contrast limited adaptive histogram equalization approach is used. For the segmentation of background cells, k-means segmentation algorithm is used because it performs better in comparison to other commonly used segmentation methods. In feature extraction phase, it is proposed to extract various biologically interpretable and clinically significant shapes as well as morphology based features from the segmented images. These include gray level texture features, color based features, color gray level texture features, Law's Texture Energy based features, Tamura's features, and wavelet features. Finally, the K-nearest neighborhood method is used for classification of images into normal and cancerous categories because it is performing better in comparison to other commonly used methods for this application. The performance of the proposed framework is evaluated using well-known parameters for four fundamental tissues (connective, epithelial, muscular, and nervous) of randomly selected 1000 microscopic biopsy images. PMID:27006938

  17. A Feature Selection Algorithm to Compute Gene Centric Methylation from Probe Level Methylation Data

    PubMed Central

    Baur, Brittany; Bozdag, Serdar

    2016-01-01

    DNA methylation is an important epigenetic event that effects gene expression during development and various diseases such as cancer. Understanding the mechanism of action of DNA methylation is important for downstream analysis. In the Illumina Infinium HumanMethylation 450K array, there are tens of probes associated with each gene. Given methylation intensities of all these probes, it is necessary to compute which of these probes are most representative of the gene centric methylation level. In this study, we developed a feature selection algorithm based on sequential forward selection that utilized different classification methods to compute gene centric DNA methylation using probe level DNA methylation data. We compared our algorithm to other feature selection algorithms such as support vector machines with recursive feature elimination, genetic algorithms and ReliefF. We evaluated all methods based on the predictive power of selected probes on their mRNA expression levels and found that a K-Nearest Neighbors classification using the sequential forward selection algorithm performed better than other algorithms based on all metrics. We also observed that transcriptional activities of certain genes were more sensitive to DNA methylation changes than transcriptional activities of other genes. Our algorithm was able to predict the expression of those genes with high accuracy using only DNA methylation data. Our results also showed that those DNA methylation-sensitive genes were enriched in Gene Ontology terms related to the regulation of various biological processes. PMID:26872146

  18. Clinical applications of gene therapy for primary immunodeficiencies.

    PubMed

    Cicalese, Maria Pia; Aiuti, Alessandro

    2015-04-01

    Primary immunodeficiencies (PIDs) have represented a paradigmatic model for successes and pitfalls of hematopoietic stem cells gene therapy. First clinical trials performed with gamma retroviral vectors (γ-RV) for adenosine deaminase severe combined immunodeficiency (ADA-SCID), X-linked SCID (SCID-X1), and Wiskott-Aldrich syndrome (WAS) showed that gene therapy is a valid therapeutic option in patients lacking an HLA-identical donor. No insertional mutagenesis events have been observed in more than 40 ADA-SCID patients treated so far in the context of different clinical trials worldwide, suggesting a favorable risk-benefit ratio for this disease. On the other hand, the occurrence of insertional oncogenesis in SCID-X1, WAS, and chronic granulomatous disease (CGD) RV clinical trials prompted the development of safer vector construct based on self-inactivating (SIN) retroviral or lentiviral vectors (LVs). Here we present the recent results of LV-mediated gene therapy for WAS showing stable multilineage engraftment leading to hematological and immunological improvement, and discuss the differences with respect to the WAS RV trial. We also describe recent clinical results of SCID-X1 gene therapy with SIN γ-RV and the perspectives of targeted genome editing techniques, following early preclinical studies showing promising results in terms of specificity of gene correction. Finally, we provide an overview of the gene therapy approaches for other PIDs and discuss its prospects in relation to the evolving arena of allogeneic transplant. PMID:25860576

  19. Use of Semisupervised Clustering and Feature-Selection Techniques for Identification of Co-expressed Genes.

    PubMed

    Saha, Sriparna; Alok, Abhay Kumar; Ekbal, Asif

    2016-07-01

    Studying the patterns hidden in gene-expression data helps to understand the functionality of genes. In general, clustering techniques are widely used for the identification of natural partitionings from the gene expression data. In order to put constraints on dimensionality, feature selection is the key issue because not all features are important from clustering point of view. Moreover some limited amount of supervised information can help to fine tune the obtained clustering solution. In this paper, the problem of simultaneous feature selection and semisupervised clustering is formulated as a multiobjective optimization (MOO) task. A modern simulated annealing-based MOO technique namely AMOSA is utilized as the background optimization methodology. Here, features and cluster centers are represented in the form of a string and the assignment of genes to different clusters is done using a point symmetry-based distance. Six optimization criteria based on several internal and external cluster validity indices are utilized. In order to generate the supervised information, a popular clustering technique, Fuzzy C-mean, is utilized. Appropriate subset of features, proper number of clusters and the proper partitioning are determined using the search capability of AMOSA. The effectiveness of this proposed semisupervised clustering technique, Semi-FeaClustMOO, is demonstrated on five publicly available benchmark gene-expression datasets. Comparison results with the existing techniques for gene-expression data clustering again reveal the superiority of the proposed technique. Statistical and biological significance tests have also been carried out. PMID:26208367

  20. ABCC8-Related Maturity-Onset Diabetes of the Young (MODY12): Clinical Features and Treatment Perspective.

    PubMed

    Ovsyannikova, Alla K; Rymar, Oksana D; Shakhtshneider, Elena V; Klimontov, Vadim V; Koroleva, Elena A; Myakina, Natalya E; Voevoda, Mikhail I

    2016-09-01

    Maturity-onset diabetes of the young (MODY) is a heterogeneous group of diseases associated with gene mutations leading to dysfunction of pancreatic β-cells. Thirteen identified MODY variants differ from each other by the clinical course and treatment requirement. Currently, MODY subtypes 1-5 are best-studied, descriptions of the other forms are sporadic. This article reports a MODY12 clinical case, caused by a mutation in the gene of the ATP-binding cassette transporter sub-family C member 8 (ABCC8), encoding sulfonylurea receptor 1. Diabetes manifested in a 27-year-old non-obese man with epilepsy in anamnesis. No evidence of ketosis was present, pancreatic antibodies were undetectable, and C-peptide remained within the reference range. During the initial investigation, non-proliferative diabetic retinopathy and elevated albumin excretion rate was revealed. After 4 months, diabetes was complicated by pre-proliferative retinopathy and diabetic macular edema. Recurrent hypoglycemia and an increase in body weight was observed on moderate and even small insulin doses. Taking into account the clinical features and the presence of diabetes in four generations on the maternal side, screening for all MODY subtypes was performed. A mutation in the ABCC8 gene was found in proband and in his mother. After the insulin discontinuation, gliclazide modified release combined with sodium/glucose cotransporter 2 (SGLT2) inhibitors was started. This treatment eliminated hypoglycemia and improved glycemic variability parameters. A decrease in the amplitude of glucose excursions was documented by continuous glucose monitoring. After 3 months of treatment, glycemic control was still optimal, and no hypoglycemic episodes were observed. The case report demonstrates the clinical features of ABCC8-associated MODY and the therapeutic potential of a combination of sulfonylurea with SGLT2 inhibitor in this disease. PMID:27538677

  1. NIMEFI: Gene Regulatory Network Inference using Multiple Ensemble Feature Importance Algorithms

    PubMed Central

    Ruyssinck, Joeri; Huynh-Thu, Vân Anh; Geurts, Pierre; Dhaene, Tom; Demeester, Piet; Saeys, Yvan

    2014-01-01

    One of the long-standing open challenges in computational systems biology is the topology inference of gene regulatory networks from high-throughput omics data. Recently, two community-wide efforts, DREAM4 and DREAM5, have been established to benchmark network inference techniques using gene expression measurements. In these challenges the overall top performer was the GENIE3 algorithm. This method decomposes the network inference task into separate regression problems for each gene in the network in which the expression values of a particular target gene are predicted using all other genes as possible predictors. Next, using tree-based ensemble methods, an importance measure for each predictor gene is calculated with respect to the target gene and a high feature importance is considered as putative evidence of a regulatory link existing between both genes. The contribution of this work is twofold. First, we generalize the regression decomposition strategy of GENIE3 to other feature importance methods. We compare the performance of support vector regression, the elastic net, random forest regression, symbolic regression and their ensemble variants in this setting to the original GENIE3 algorithm. To create the ensemble variants, we propose a subsampling approach which allows us to cast any feature selection algorithm that produces a feature ranking into an ensemble feature importance algorithm. We demonstrate that the ensemble setting is key to the network inference task, as only ensemble variants achieve top performance. As second contribution, we explore the effect of using rankwise averaged predictions of multiple ensemble algorithms as opposed to only one. We name this approach NIMEFI (Network Inference using Multiple Ensemble Feature Importance algorithms) and show that this approach outperforms all individual methods in general, although on a specific network a single method can perform better. An implementation of NIMEFI has been made publicly available

  2. Co-existence of various clinical and histopathological features of mycosis fungoides in a young female.

    PubMed

    Naeini, Farahnaz Fatemi; Soghrati, Mehrnaz; Abtahi-Naeini, Bahareh; Najafian, Jamshid; Rajabi, Parvin

    2015-01-01

    Mycosis fungoides is the most common type of cutaneous T-cell lymphoma (CTCL) and a rare disorder that typically affects older adults with erythematous scaling patches and plaques. Hypopigmented patches are a rare clinical variant of the disease. Granulomatous mycosis fungoides (GMF) is also a rare type of CTCL. No particular clinical criteria are available for the diagnosis of GMF, because of its variable presentations, and so the detection of GMF is primarily considered as a histopathological diagnosis. Rarely, a co-existence of more than one clinical or histopathological feature of mycosis fungoides may be present. To the best of our knowledge this is the first report of MF that shows the simultaneous co-existence of more than one clinical and histopathological variant of MF. We present a 29-year-old female with clinical presentations of both classic and hypopigmented mycosis fungoides (MF), and also the histopathological features of the classic and granulomatous types of the disease. PMID:25814741

  3. Co-Existence of Various Clinical and Histopathological Features of Mycosis Fungoides in a Young Female

    PubMed Central

    Naeini, Farahnaz Fatemi; Soghrati, Mehrnaz; Abtahi-Naeini, Bahareh; Najafian, Jamshid; Rajabi, Parvin

    2015-01-01

    Mycosis fungoides is the most common type of cutaneous T-cell lymphoma (CTCL) and a rare disorder that typically affects older adults with erythematous scaling patches and plaques. Hypopigmented patches are a rare clinical variant of the disease. Granulomatous mycosis fungoides (GMF) is also a rare type of CTCL. No particular clinical criteria are available for the diagnosis of GMF, because of its variable presentations, and so the detection of GMF is primarily considered as a histopathological diagnosis. Rarely, a co-existence of more than one clinical or histopathological feature of mycosis fungoides may be present. To the best of our knowledge this is the first report of MF that shows the simultaneous co-existence of more than one clinical and histopathological variant of MF. We present a 29-year-old female with clinical presentations of both classic and hypopigmented mycosis fungoides (MF), and also the histopathological features of the classic and granulomatous types of the disease. PMID:25814741

  4. Cognitive Impairment and Dementia in Parkinson’s Disease: Clinical Features, Diagnosis, and Management

    PubMed Central

    Meireles, Joana; Massano, João

    2012-01-01

    Parkinson’s disease (PD) is a common, disabling, neurodegenerative disorder. In addition to classical motor symptoms, non-motor features are now widely accepted as part of the clinical picture, and cognitive decline is a very important aspect of the disease, as it brings an additional significant burden for the patient and caregivers. The diagnosis of cognitive decline in PD, namely mild cognitive impairment (MCI) and dementia, can be extremely challenging, remaining largely based on clinical and cognitive assessments. Diagnostic criteria and methods for PD dementia and MCI have been recently issued by expert work groups. This manuscript has synthesized relevant data in order to obtain a pragmatic and updated review regarding cognitive decline in PD, from milder stages to dementia. This text will summarize clinical features, diagnostic methodology, and therapeutic issues of clinical decline in PD. Relevant clinical genetic issues, including recent advances, will also be approached. PMID:22654785

  5. Gene therapy clinical trials worldwide 1989-2004-an overview.

    PubMed

    Edelstein, Michael L; Abedi, Mohammad R; Wixon, Jo; Edelstein, Richard M

    2004-06-01

    In 1989, Rosenberg et al. performed the first human gene therapy trial when they used a retrovirus to introduce the gene coding for resistance to neomycin into human tumor-infiltrating lymphocytes before infusing them into five patients with advanced melanoma. This study demonstrated the feasibility of using retroviral gene transduction in humans and set the stage for further studies. Since then, over 900 clinical trials have been completed, are ongoing or have been approved worldwide. These trials have been designed to establish feasibility and safety, to demonstrate the reality of expression of therapeutic protein(s) in vivo by the genes transferred and, in some cases, to show therapeutic benefit. There is no single source of information that presents an overview of all the clinical trials undertaken worldwide. In 1997 we set up a database to bring all the information on clinical trials together as comprehensively and as globally as possible. The data were compiled and are regularly updated from official agency sources, the published literature, presentations at conferences and from information kindly provided by investigators or trial sponsors themselves. As of January 31, 2004, we have identified 918 trials in 24 countries. The USA accounts for two-thirds of these trials. Cancer is by far the most common disease indication, followed by inherited monogenic diseases, and cardiovascular diseases. Viral vectors have been the most frequently used vehicles for transferring genes into human cells, with retroviruses and adenoviruses representing the vast majority. Plasmid (naked) DNA and other non-viral vectors have been used in one-quarter of the trials. Over 100 distinct genes have been transferred. This article aims to provide a descriptive overview of the clinical trials that, to the best of our knowledge, have been or are being performed worldwide. Details of the data presented, including an interactive, searchable database that currently holds information on 918

  6. Uncovering major genomic features of essential genes in Bacteria and a methanogenic Archaea.

    PubMed

    Grazziotin, Ana Laura; Vidal, Newton M; Venancio, Thiago M

    2015-09-01

    Identification of essential genes is critical to understanding the physiology of a species, proposing novel drug targets and uncovering minimal gene sets required for life. Although essential gene sets of several organisms have been determined using large-scale mutagenesis techniques, systematic studies addressing their conservation, genomic context and functions remain scant. Here we integrate 17 essential gene sets from genome-wide in vitro screenings and three gene collections required for growth in vivo, encompassing 15 Bacteria and one Archaea. We refine and generalize important theories proposed using Escherichia coli. Essential genes are typically monogenic and more conserved than nonessential genes. Genes required in vivo are less conserved than those essential in vitro, suggesting that more divergent strategies are deployed when the organism is stressed by the host immune system and unstable nutrient availability. We identified essential analogous pathways that would probably be missed by orthology-based essentiality prediction strategies. For example, Streptococcus sanguinis carries horizontally transferred isoprenoid biosynthesis genes that are widespread in Archaea. Genes specifically essential in Mycobacterium tuberculosis and Burkholderia pseudomallei are reported as potential drug targets. Moreover, essential genes are not only preferentially located in operons, but also occupy the first position therein, supporting the influence of their regulatory regions in driving transcription of whole operons. Finally, these important genomic features are shared between Bacteria and at least one Archaea, suggesting that high order properties of gene essentiality and genome architecture were probably present in the last universal common ancestor or evolved independently in the prokaryotic domains. PMID:26084810

  7. Detection of EML4-ALK fusion gene and features associated with EGFR mutations in Chinese patients with non-small-cell lung cancer

    PubMed Central

    Wen, Miaomiao; Wang, Xuejiao; Sun, Ying; Xia, Jinghua; Fan, Liangbo; Xing, Hao; Zhang, Zhipei; Li, Xiaofei

    2016-01-01

    Purpose Echinoderm microtubule-associated protein-like 4–anaplastic lymphoma kinase (EML4-ALK) and epidermal growth factor receptor (EGFR) define specific molecular subsets of lung cancer with distinct clinical features. We aimed at revealing the clinical features of EML4-ALK fusion gene and EGFR mutation in non-small-cell lung cancer (NSCLC). Methods We enrolled 694 Chinese patients with NSCLC for analysis. EML4-ALK fusion gene was analyzed by real-time polymerase chain reaction, and EGFR mutations were analyzed by amplified refractory mutation system. Results Among the 694 patients, 60 (8.65%) patients had EML4-ALK fusions. In continuity correction χ2 test analysis, EML4-ALK fusion gene was correlated with sex, age, smoking status, and histology, but no significant association was observed between EML4-ALK fusion gene and clinical stage. A total of 147 (21.18%) patients had EGFR mutations. In concordance with previous reports, EGFR mutation was correlated with age, smoking status, histology, and clinical stage, whereas patient age was not significantly associated with EGFR mutation. Meanwhile, to our surprise, six (0.86%) patients had coexisting EML4-ALK fusions and EGFR mutations. Conclusion EML4-ALK fusion gene defines a new molecular subset in patients with NSCLC. Six patients who harbored both EML4-ALK fusion genes and EGFR mutations were identified in our study. The EGFR mutations and the EML4-ALK fusion genes are coexistent. PMID:27103824

  8. Clinical and genetic features of dyskeratosis congenita, cryptic dyskeratosis congenita, and Hoyeraal-Hreidarsson syndrome in Japan.

    PubMed

    Yamaguchi, Hiroki; Sakaguchi, Hirotoshi; Yoshida, Kenichi; Yabe, Miharu; Yabe, Hiromasa; Okuno, Yusuke; Muramatsu, Hideki; Takahashi, Yoshiyuki; Yui, Shunsuke; Shiraishi, Yuichi; Chiba, Kenichi; Tanaka, Hiroko; Miyano, Satoru; Inokuchi, Koiti; Ito, Etsuro; Ogawa, Seishi; Kojima, Seiji

    2015-11-01

    Dyskeratosis congenita (DKC) is an inherited bone marrow failure (BMF) syndrome typified by reticulated skin pigmentation, nail dystrophy, and mucosal leukoplakia. Hoyeraal-Hreidarsson syndrome (HHS) is considered to be a severe form of DKC. Unconventional forms of DKC, which develop slowly in adulthood but without the physical anomalies characteristic of DKC (cryptic DKC), have been reported. Clinical and genetic features of DKC have been investigated in Caucasian, Black, and Hispanic populations, but not in Asian populations. The present study aimed to determine the clinical and genetic features of DKC, HHS, and cryptic DKC among Japanese patients. We analyzed 16 patients diagnosed with DKC, three patients with HHS, and 15 patients with cryptic DKC. We found that platelet count was significantly more depressed than neutrophil count or hemoglobin value in DKC patients, and identified DKC patients with large deletions in the telomerase reverse transcriptase and cryptic DKC patients with RTEL1 mutations on both alleles. This led to some patients previously considered to have unclassifiable BMF being diagnosed with cDKC through identification of new gene mutations. It thus seems important from a clinical viewpoint to re-examine the clinical characteristics, frequency of genetic mutations, and treatment efficacy in DKC, HHS, and cDKC. PMID:26329388

  9. A Novel Method Incorporating Gene Ontology Information for Unsupervised Clustering and Feature Selection

    PubMed Central

    Srivastava, Shireesh; Zhang, Linxia; Jin, Rong; Chan, Christina

    2008-01-01

    Background Among the primary goals of microarray analysis is the identification of genes that could distinguish between different phenotypes (feature selection). Previous studies indicate that incorporating prior information of the genes' function could help identify physiologically relevant features. However, current methods that incorporate prior functional information do not provide a relative estimate of the effect of different genes on the biological processes of interest. Results Here, we present a method that integrates gene ontology (GO) information and expression data using Bayesian regression mixture models to perform unsupervised clustering of the samples and identify physiologically relevant discriminating features. As a model application, the method was applied to identify the genes that play a role in the cytotoxic responses of human hepatoblastoma cell line (HepG2) to saturated fatty acid (SFA) and tumor necrosis factor (TNF)-α, as compared to the non-toxic response to the unsaturated FFAs (UFA) and TNF-α. Incorporation of prior knowledge led to a better discrimination of the toxic phenotypes from the others. The model identified roles of lysosomal ATPases and adenylate cyclase (AC9) in the toxicity of palmitate. To validate the role of AC in palmitate-treated cells, we measured the intracellular levels of cyclic AMP (cAMP). The cAMP levels were found to be significantly reduced by palmitate treatment and not by the other FFAs, in accordance with the model selection of AC9. Conclusions A framework is presented that incorporates prior ontology information, which helped to (a) perform unsupervised clustering of the phenotypes, and (b) identify the genes relevant to each cluster of phenotypes. We demonstrate the proposed framework by applying it to identify physiologically-relevant feature genes that conferred differential toxicity to saturated vs. unsaturated FFAs. The framework can be applied to other problems to efficiently integrate ontology

  10. Hybrid Binary Imperialist Competition Algorithm and Tabu Search Approach for Feature Selection Using Gene Expression Data.

    PubMed

    Wang, Shuaiqun; Aorigele; Kong, Wei; Zeng, Weiming; Hong, Xiaomin

    2016-01-01

    Gene expression data composed of thousands of genes play an important role in classification platforms and disease diagnosis. Hence, it is vital to select a small subset of salient features over a large number of gene expression data. Lately, many researchers devote themselves to feature selection using diverse computational intelligence methods. However, in the progress of selecting informative genes, many computational methods face difficulties in selecting small subsets for cancer classification due to the huge number of genes (high dimension) compared to the small number of samples, noisy genes, and irrelevant genes. In this paper, we propose a new hybrid algorithm HICATS incorporating imperialist competition algorithm (ICA) which performs global search and tabu search (TS) that conducts fine-tuned search. In order to verify the performance of the proposed algorithm HICATS, we have tested it on 10 well-known benchmark gene expression classification datasets with dimensions varying from 2308 to 12600. The performance of our proposed method proved to be superior to other related works including the conventional version of binary optimization algorithm in terms of classification accuracy and the number of selected genes. PMID:27579323

  11. Hybrid Binary Imperialist Competition Algorithm and Tabu Search Approach for Feature Selection Using Gene Expression Data

    PubMed Central

    Aorigele; Zeng, Weiming; Hong, Xiaomin

    2016-01-01

    Gene expression data composed of thousands of genes play an important role in classification platforms and disease diagnosis. Hence, it is vital to select a small subset of salient features over a large number of gene expression data. Lately, many researchers devote themselves to feature selection using diverse computational intelligence methods. However, in the progress of selecting informative genes, many computational methods face difficulties in selecting small subsets for cancer classification due to the huge number of genes (high dimension) compared to the small number of samples, noisy genes, and irrelevant genes. In this paper, we propose a new hybrid algorithm HICATS incorporating imperialist competition algorithm (ICA) which performs global search and tabu search (TS) that conducts fine-tuned search. In order to verify the performance of the proposed algorithm HICATS, we have tested it on 10 well-known benchmark gene expression classification datasets with dimensions varying from 2308 to 12600. The performance of our proposed method proved to be superior to other related works including the conventional version of binary optimization algorithm in terms of classification accuracy and the number of selected genes. PMID:27579323

  12. A comparison of clinical features among Japanese eating-disordered women with obsessive-compulsive disorder.

    PubMed

    Matsunaga, H; Miyata, A; Iwasaki, Y; Matsui, T; Fujimoto, K; Kiriike, N

    1999-01-01

    Clinical features, such as obsessive-compulsive disorder (OCD) symptoms, were investigated in Japanese women with DSM-III-R eating disorders (EDs) and concurrent OCD in comparison to age-matched women with OCD. Sixteen women with restricting anorexia nervosa (AN), 16 with bulimia nervosa (BN), and 16 with both AN and BN (BAN) showed commonality in a more elevated prevalence of OCD symptoms of symmetry and order compared with 18 OCD women. Among the personality disorders (PDs), likewise, obsessive-compulsive PD (OCPD) was more prevalent in each ED group compared with the OCD group. However, aggressive obsessions were more common in both BN and BAN subjects compared with AN subjects. Subjects with bulimic symptoms were also distinguished from AN subjects by impulsive features in behavior and personality. Thus, an elevated prevalence of aggressive obsessions along with an admixture of impulsive and compulsive features specifically characterized the clinical features of bulimic subjects with OCD. PMID:10509614

  13. Evaluation of features to support safety and quality in general practice clinical software

    PubMed Central

    2011-01-01

    Background Electronic prescribing is now the norm in many countries. We wished to find out if clinical software systems used by general practitioners in Australia include features (functional capabilities and other characteristics) that facilitate improved patient safety and care, with a focus on quality use of medicines. Methods Seven clinical software systems used in general practice were evaluated. Fifty software features that were previously rated as likely to have a high impact on safety and/or quality of care in general practice were tested and are reported here. Results The range of results for the implementation of 50 features across the 7 clinical software systems was as follows: 17-31 features (34-62%) were fully implemented, 9-13 (18-26%) partially implemented, and 9-20 (18-40%) not implemented. Key findings included: Access to evidence based drug and therapeutic information was limited. Decision support for prescribing was available but varied markedly between systems. During prescribing there was potential for medicine mis-selection in some systems, and linking a medicine with its indication was optional. The definition of 'current medicines' versus 'past medicines' was not always clear. There were limited resources for patients, and some medicines lists for patients were suboptimal. Results were provided to the software vendors, who were keen to improve their systems. Conclusions The clinical systems tested lack some of the features expected to support patient safety and quality of care. Standards and certification for clinical software would ensure that safety features are present and that there is a minimum level of clinical functionality that clinicians could expect to find in any system.

  14. Serologic features of primary Sjögren’s syndrome: clinical and prognostic correlation

    PubMed Central

    García-Carrasco, Mario; Mendoza-Pinto, Claudia; Jiménez-Hernández, César; Jiménez-Hernández, Mario; Nava-Zavala, Arnulfo; Riebeling, Carlos

    2013-01-01

    Sjögren’s syndrome (SS) is a chronic inflammatory systemic autoimmune disease. The disease spectrum extends from sicca syndrome to systemic involvement and extraglandular manifestations, and SS may be associated with malignancies, especially non-Hodgkin’s lymphoma. Patients with SS present a broad spectrum of serologic features. Certain serological findings are highly correlated with specific clinical features, and can be used as prognostic markers. PMID:23525186

  15. Prediction models for solitary pulmonary nodules based on curvelet textural features and clinical parameters.

    PubMed

    Wang, Jing-Jing; Wu, Hai-Feng; Sun, Tao; Li, Xia; Wang, Wei; Tao, Li-Xin; Huo, Da; Lv, Ping-Xin; He, Wen; Guo, Xiu-Hua

    2013-01-01

    Lung cancer, one of the leading causes of cancer-related deaths, usually appears as solitary pulmonary nodules (SPNs) which are hard to diagnose using the naked eye. In this paper, curvelet-based textural features and clinical parameters are used with three prediction models [a multilevel model, a least absolute shrinkage and selection operator (LASSO) regression method, and a support vector machine (SVM)] to improve the diagnosis of benign and malignant SPNs. Dimensionality reduction of the original curvelet-based textural features was achieved using principal component analysis. In addition, non-conditional logistical regression was used to find clinical predictors among demographic parameters and morphological features. The results showed that, combined with 11 clinical predictors, the accuracy rates using 12 principal components were higher than those using the original curvelet-based textural features. To evaluate the models, 10-fold cross validation and back substitution were applied. The results obtained, respectively, were 0.8549 and 0.9221 for the LASSO method, 0.9443 and 0.9831 for SVM, and 0.8722 and 0.9722 for the multilevel model. All in all, it was found that using curvelet-based textural features after dimensionality reduction and using clinical predictors, the highest accuracy rate was achieved with SVM. The method may be used as an auxiliary tool to differentiate between benign and malignant SPNs in CT images. PMID:24289618

  16. Solid organ abdominal ischemia, part I: clinical features, etiology, imaging findings, and management.

    PubMed

    Ricci, Zina J; Oh, Sarah K; Stein, Marjorie W; Kaul, Bindu; Flusberg, Milana; Chernyak, Victoria; Rozenblit, Alla M; Mazzariol, Fernanda A

    2016-01-01

    Solid organ abdominal ischemia commonly presents with acute pain prompting radiologic evaluation and often requires urgent treatment. Despite different risk factors and anatomic differences, most solid organ ischemia is due to arterial or venous occlusion and, less frequently, a low-flow state. Radiologic diagnosis is critical, as clinical presentations are often nonspecific. Contrast-enhanced computed tomography (CT) is the modality of choice (except in adnexal torsion) with magnetic resonance imaging (MRI) useful in equivocal cases or follow-up of ischemic disease. This article will provide a pictorial review of the CT and MRI features of solid abdominal organ ischemia while highlighting key clinical features, etiology, and management. PMID:27317217

  17. Clinical Significance of Histological Features of Thrombi in Patients with Myocardial Infarction

    PubMed Central

    Sebben, Juliana Canedo; Cambruzzi, Eduardo; Avena, Luisa Martins; Gazeta, Cristina do Amaral; Gottschall, Carlos Antonio Mascia; de Quadros, Alexandre Schaan

    2013-01-01

    Background Percutaneous Coronary Intervention (PCI) is the most common strategy for the treatment of Acute ST segment elevation Myocardial Infarction (STEMI), and thromboaspiration has been increasingly utilized for removal of occlusive thrombi. Objectives To analyze the influence of histopathological features of coronary thrombi in clinical outcomes of patients with STEMI, and the association of these variables with clinical, angiographic, and laboratory features and medications used in hospitalization. Methods Prospective cohort study. All patients were monitored during hospitalization and thirty days after the event. Aspirated thrombi were preserved in formalin and subsequently stained with hematoxylin-eosin and embedded in paraffin. Thrombi were classified as recent and old. The primary outcome was the occurrence of major cardiovascular events within thirty days. Results During the study period, 1,149 patients were evaluated with STEMI, and 331 patients underwent thrombi aspiration, leaving 199 patients available for analysis. It was identified recent thrombi in 116 patients (58%) and old thrombi in 83 patients (42%). Recent thrombi have greater infiltration of red blood cells than old thrombi (p = 0.02), but there were no statistically significant differences between other clinical, angiographic, laboratory, and histopathological features and medications in both group of patients. The rates of clinical outcomes were similar in both groups. Conclusions Recent thrombi were identified in 58% of patients with STEMI and it was observed an association with infiltration of red blood cells. There was no association between histopathological features of thrombi and clinical variables and cardiovascular outcomes. PMID:24162472

  18. Relational Network for Knowledge Discovery through Heterogeneous Biomedical and Clinical Features

    PubMed Central

    Chen, Huaidong; Chen, Wei; Liu, Chenglin; Zhang, Le; Su, Jing; Zhou, Xiaobo

    2016-01-01

    Biomedical big data, as a whole, covers numerous features, while each dataset specifically delineates part of them. “Full feature spectrum” knowledge discovery across heterogeneous data sources remains a major challenge. We developed a method called bootstrapping for unified feature association measurement (BUFAM) for pairwise association analysis, and relational dependency network (RDN) modeling for global module detection on features across breast cancer cohorts. Discovered knowledge was cross-validated using data from Wake Forest Baptist Medical Center’s electronic medical records and annotated with BioCarta signaling signatures. The clinical potential of the discovered modules was exhibited by stratifying patients for drug responses. A series of discovered associations provided new insights into breast cancer, such as the effects of patient’s cultural background on preferences for surgical procedure. We also discovered two groups of highly associated features, the HER2 and the ER modules, each of which described how phenotypes were associated with molecular signatures, diagnostic features, and clinical decisions. The discovered “ER module”, which was dominated by cancer immunity, was used as an example for patient stratification and prediction of drug responses to tamoxifen and chemotherapy. BUFAM-derived RDN modeling demonstrated unique ability to discover clinically meaningful and actionable knowledge across highly heterogeneous biomedical big data sets. PMID:27427091

  19. Relational Network for Knowledge Discovery through Heterogeneous Biomedical and Clinical Features

    NASA Astrophysics Data System (ADS)

    Chen, Huaidong; Chen, Wei; Liu, Chenglin; Zhang, Le; Su, Jing; Zhou, Xiaobo

    2016-07-01

    Biomedical big data, as a whole, covers numerous features, while each dataset specifically delineates part of them. “Full feature spectrum” knowledge discovery across heterogeneous data sources remains a major challenge. We developed a method called bootstrapping for unified feature association measurement (BUFAM) for pairwise association analysis, and relational dependency network (RDN) modeling for global module detection on features across breast cancer cohorts. Discovered knowledge was cross-validated using data from Wake Forest Baptist Medical Center’s electronic medical records and annotated with BioCarta signaling signatures. The clinical potential of the discovered modules was exhibited by stratifying patients for drug responses. A series of discovered associations provided new insights into breast cancer, such as the effects of patient’s cultural background on preferences for surgical procedure. We also discovered two groups of highly associated features, the HER2 and the ER modules, each of which described how phenotypes were associated with molecular signatures, diagnostic features, and clinical decisions. The discovered “ER module”, which was dominated by cancer immunity, was used as an example for patient stratification and prediction of drug responses to tamoxifen and chemotherapy. BUFAM-derived RDN modeling demonstrated unique ability to discover clinically meaningful and actionable knowledge across highly heterogeneous biomedical big data sets.

  20. Relational Network for Knowledge Discovery through Heterogeneous Biomedical and Clinical Features.

    PubMed

    Chen, Huaidong; Chen, Wei; Liu, Chenglin; Zhang, Le; Su, Jing; Zhou, Xiaobo

    2016-01-01

    Biomedical big data, as a whole, covers numerous features, while each dataset specifically delineates part of them. "Full feature spectrum" knowledge discovery across heterogeneous data sources remains a major challenge. We developed a method called bootstrapping for unified feature association measurement (BUFAM) for pairwise association analysis, and relational dependency network (RDN) modeling for global module detection on features across breast cancer cohorts. Discovered knowledge was cross-validated using data from Wake Forest Baptist Medical Center's electronic medical records and annotated with BioCarta signaling signatures. The clinical potential of the discovered modules was exhibited by stratifying patients for drug responses. A series of discovered associations provided new insights into breast cancer, such as the effects of patient's cultural background on preferences for surgical procedure. We also discovered two groups of highly associated features, the HER2 and the ER modules, each of which described how phenotypes were associated with molecular signatures, diagnostic features, and clinical decisions. The discovered "ER module", which was dominated by cancer immunity, was used as an example for patient stratification and prediction of drug responses to tamoxifen and chemotherapy. BUFAM-derived RDN modeling demonstrated unique ability to discover clinically meaningful and actionable knowledge across highly heterogeneous biomedical big data sets. PMID:27427091

  1. Identifying Potential Clinical Syndromes of Hepatocellular Carcinoma Using PSO-Based Hierarchical Feature Selection Algorithm

    PubMed Central

    Ji, Zhiwei; Wang, Bing

    2014-01-01

    Hepatocellular carcinoma (HCC) is one of the most common malignant tumors. Clinical symptoms attributable to HCC are usually absent, thus often miss the best therapeutic opportunities. Traditional Chinese Medicine (TCM) plays an active role in diagnosis and treatment of HCC. In this paper, we proposed a particle swarm optimization-based hierarchical feature selection (PSOHFS) model to infer potential syndromes for diagnosis of HCC. Firstly, the hierarchical feature representation is developed by a three-layer tree. The clinical symptoms and positive score of patient are leaf nodes and root in the tree, respectively, while each syndrome feature on the middle layer is extracted from a group of symptoms. Secondly, an improved PSO-based algorithm is applied in a new reduced feature space to search an optimal syndrome subset. Based on the result of feature selection, the causal relationships of symptoms and syndromes are inferred via Bayesian networks. In our experiment, 147 symptoms were aggregated into 27 groups and 27 syndrome features were extracted. The proposed approach discovered 24 syndromes which obviously improved the diagnosis accuracy. Finally, the Bayesian approach was applied to represent the causal relationships both at symptom and syndrome levels. The results show that our computational model can facilitate the clinical diagnosis of HCC. PMID:24745007

  2. Prediction of core cancer genes using a hybrid of feature selection and machine learning methods.

    PubMed

    Liu, Y X; Zhang, N N; He, Y; Lun, L J

    2015-01-01

    Machine learning techniques are of great importance in the analysis of microarray expression data, and provide a systematic and promising way to predict core cancer genes. In this study, a hybrid strategy was introduced based on machine learning techniques to select a small set of informative genes, which will lead to improving classification accuracy. First feature filtering algorithms were applied to select a set of top-ranked genes, and then hierarchical clustering and collapsing dense clusters were used to select core cancer genes. Through empirical study, our approach is capable of selecting relatively few core cancer genes while making high-accuracy predictions. The biological significance of these genes was evaluated using systems biology analysis. Extensive functional pathway and network analyses have confirmed findings in previous studies and can bring new insights into common cancer mechanisms. PMID:26345818

  3. Resistance Mechanisms and Clinical Features of Fluconazole-Nonsusceptible Candida tropicalis Isolates Compared with Fluconazole-Less-Susceptible Isolates.

    PubMed

    Choi, Min Ji; Won, Eun Jeong; Shin, Jong Hee; Kim, Soo Hyun; Lee, Wee-Gyo; Kim, Mi-Na; Lee, Kyungwon; Shin, Myung Geun; Suh, Soon Pal; Ryang, Dong Wook; Im, Young Jun

    2016-06-01

    We investigated the azole resistance mechanisms and clinical features of fluconazole-nonsusceptible (FNS) isolates of Candida tropicalis recovered from Korean surveillance cultures in comparison with fluconazole-less-susceptible (FLS) isolates. Thirty-five clinical isolates of C. tropicalis, comprising 9 FNS (fluconazole MIC, 4 to 64 μg/ml), 12 FLS (MIC, 1 to 2 μg/ml), and 14 control (MIC, 0.125 to 0.5 μg/ml) isolates, were assessed. CDR1, MDR1, and ERG11 expression was quantified, and the ERG11 and UPC2 genes were sequenced. Clinical features of 16 patients with FNS or FLS bloodstream isolates were analyzed. Both FNS and FLS isolates had >10-fold higher mean expression levels of CDR1, MDR1, and ERG11 genes than control isolates (P values of <0.02 for all). When FNS and FLS isolates were compared, FNS isolates had 3.4-fold higher mean ERG11 expression levels than FLS isolates (P = 0.004), but there were no differences in those of CDR1 or MDR1 Of all 35 isolates, 4 (2 FNS and 2 FLS) and 28 (8 FNS, 11 FLS, and 9 control) isolates exhibited amino acid substitutions in Erg11p and Upc2p, respectively. Both FNS and FLS bloodstream isolates were associated with azole therapeutic failure (3/4 versus 4/7) or uncleared fungemia (4/6 versus 4/10), but FNS isolates were identified more frequently from patients with previous azole exposure (6/6 versus 3/10; P = 0.011) and immunosuppression (6/6 versus 3/10; P = 0.011). These results reveal that the majority of FNS C. tropicalis isolates show overexpression of CDR1, MDR1, and ERG11 genes, and fungemia develops after azole exposure in patients with immunosuppression. PMID:27044550

  4. The organization structure and regulatory elements of Chlamydomonas histone genes reveal features linking plant and animal genes.

    PubMed

    Fabry, S; Müller, K; Lindauer, A; Park, P B; Cornelius, T; Schmitt, R

    1995-09-01

    (66% identity). Organization of the core histone gene in pairs, and non-polyadenylation of mRNAs are features shared with animals, whereas peptide sequences and enhancer elements are shared with higher plants, assigning the volvocalean histone genes a position intermediate between animals and plants. PMID:8590479

  5. Different mutations at V363 MAPT codon are associated with atypical clinical phenotypes and show unusual structural and functional features.

    PubMed

    Rossi, Giacomina; Bastone, Antonio; Piccoli, Elena; Morbin, Michela; Mazzoleni, Giulia; Fugnanesi, Valeria; Beeg, Marten; Del Favero, Elena; Cantù, Laura; Motta, Simona; Salsano, Ettore; Pareyson, Davide; Erbetta, Alessandra; Elia, Antonio Emanuele; Del Sorbo, Francesca; Silani, Vincenzo; Morelli, Claudia; Salmona, Mario; Tagliavini, Fabrizio

    2014-02-01

    Microtubule-associated protein tau gene (MAPT) is one of the major genes linked to frontotemporal lobar degeneration, a group of neurodegenerative diseases clinically, pathologically, and genetically heterogeneous. In particular, MAPT mutations give rise to the subgroup of tauopathies. The pathogenetic mechanisms underlying the MAPT mutations so far described are the decreased ability of tau protein to promote microtubule polymerization (missense mutations) or the altered ratio of tau isoforms (splicing mutations), both leading to accumulation of hyperphosphorylated filamentous tau protein. Following a genetic screening of patients affected by frontotemporal lobar degeneration, we identified 2 MAPT mutations, V363I and V363A, leading to atypical clinical phenotypes, such as posterior cortical atrophy. We investigated in vitro features of the recombinant mutated tau isoforms and revealed unusual functional and structural characteristics such as an increased ability to promote microtubule polymerization and a tendency to form oligomeric instead of filamentous aggregates. Thus, we disclosed a greater than expected complexity of abnormal features of mutated tau isoforms. Overall our findings suggest a high probability that these mutations are pathogenic. PMID:24018212

  6. Feature genes predicting the FLT3/ITD mutation in acute myeloid leukemia.

    PubMed

    Li, Chenglong; Zhu, Biao; Chen, Jiao; Huang, Xiaobing

    2016-07-01

    In the present study, gene expression profiles of acute myeloid leukemia (AML) samples were analyzed to identify feature genes with the capacity to predict the mutation status of FLT3/ITD. Two machine learning models, namely the support vector machine (SVM) and random forest (RF) methods, were used for classification. Four datasets were downloaded from the European Bioinformatics Institute, two of which (containing 371 samples, including 281 FLT3/ITD mutation-negative and 90 mutation‑positive samples) were randomly defined as the training group, while the other two datasets (containing 488 samples, including 350 FLT3/ITD mutation-negative and 138 mutation-positive samples) were defined as the test group. Differentially expressed genes (DEGs) were identified by significance analysis of the microarray data by using the training samples. The classification efficiency of the SCM and RF methods was evaluated using the following parameters: Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and the area under the receiver operating characteristic curve. Functional enrichment analysis was performed for the feature genes with DAVID. A total of 585 DEGs were identified in the training group, of which 580 were upregulated and five were downregulated. The classification accuracy rates of the two methods for the training group, the test group and the combined group using the 585 feature genes were >90%. For the SVM and RF methods, the rates of correct determination, specificity and PPV were >90%, while the sensitivity and NPV were >80%. The SVM method produced a slightly better classification effect than the RF method. A total of 13 biological pathways were overrepresented by the feature genes, mainly involving energy metabolism, chromatin organization and translation. The feature genes identified in the present study may be used to predict the mutation status of FLT3/ITD in patients with AML. PMID:27177049

  7. Feature genes predicting the FLT3/ITD mutation in acute myeloid leukemia

    PubMed Central

    LI, CHENGLONG; ZHU, BIAO; CHEN, JIAO; HUANG, XIAOBING

    2016-01-01

    In the present study, gene expression profiles of acute myeloid leukemia (AML) samples were analyzed to identify feature genes with the capacity to predict the mutation status of FLT3/ITD. Two machine learning models, namely the support vector machine (SVM) and random forest (RF) methods, were used for classification. Four datasets were downloaded from the European Bioinformatics Institute, two of which (containing 371 samples, including 281 FLT3/ITD mutation-negative and 90 mutation-positive samples) were randomly defined as the training group, while the other two datasets (containing 488 samples, including 350 FLT3/ITD mutation-negative and 138 mutation-positive samples) were defined as the test group. Differentially expressed genes (DEGs) were identified by significance analysis of the micro-array data by using the training samples. The classification efficiency of the SCM and RF methods was evaluated using the following parameters: Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and the area under the receiver operating characteristic curve. Functional enrichment analysis was performed for the feature genes with DAVID. A total of 585 DEGs were identified in the training group, of which 580 were upregulated and five were downregulated. The classification accuracy rates of the two methods for the training group, the test group and the combined group using the 585 feature genes were >90%. For the SVM and RF methods, the rates of correct determination, specificity and PPV were >90%, while the sensitivity and NPV were >80%. The SVM method produced a slightly better classification effect than the RF method. A total of 13 biological pathways were overrepresented by the feature genes, mainly involving energy metabolism, chromatin organization and translation. The feature genes identified in the present study may be used to predict the mutation status of FLT3/ITD in patients with AML. PMID:27177049

  8. Oral lichen planus: the clinical, historical, and therapeutic features of 100 cases.

    PubMed

    Vincent, S D; Fotos, P G; Baker, K A; Williams, T P

    1990-08-01

    Lichen planus is a chronic inflammatory epidermal and mucosal disease, the cause of which is poorly understood. We reviewed the clinical and historic features of 100 patients referred to our clinic for diagnosis and management of lichen planus. The age, gender, chief complaint, duration of the chief complaint, medical history, medications, and clinical findings were recorded. Past therapeutic modalities were reviewed. Of therapeutic significance, 25 patients with oral lichen planus had a secondary oral candidiasis. Management of symptomatic lichen planus with topical and systemic steroid is discussed. The pharmacology of topical and systemic steroid usage and the rationale for treatment are discussed. PMID:2290644

  9. Distinct Clinic-Pathological Features of Early Differentiated-Type Gastric Cancers after Helicobacter pylori Eradication.

    PubMed

    Horiguchi, Noriyuki; Tahara, Tomomitsu; Kawamura, Tomohiko; Okubo, Masaaki; Ishizuka, Takamitsu; Nakagawa, Yoshihito; Nagasaka, Mitsuo; Shibata, Tomoyuki; Ohmiya, Naoki

    2016-01-01

    Background. Gastric cancer is discovered even after successful eradication of H. pylori. We investigated clinic pathological features of early gastric cancers after H. pylori eradication. Methods. 51 early gastric cancers (EGCs) from 44 patients diagnosed after successful H. pylori eradication were included as eradication group. The clinic-pathological features were compared with that of 131 EGCs from 120 patients who did not have a history of H. pylori eradication (control group). Results. Compared with control group, clinic-pathological features of eradication group were characterized as depressed (p < 0.0001), reddish (p = 0.0001), and smaller (p = 0.0095) lesions, which was also confirmed in the comparison of six metachronous lesions diagnosed after initial ESD and subsequent successful H. pylori eradication. Prevalence of both SM2 (submucosal invasion greater than 500 μm) and unexpected SM2 cases tended to be higher in eradication group (p = 0.077, 0.0867, resp.). Prevalence of inconclusive diagnosis of gastric cancer during pretreatment biopsy was also higher in the same group (26.0% versus 1.6%, p < 0.0001). Conclusions. Informative clinic pathological features of EGC after H. pylori eradication are depressed, reddish appearances, which should be treated as a caution because histological diagnosis of cancerous tissue is sometimes difficult by endoscopic biopsy. PMID:27212944

  10. Distinct Clinic-Pathological Features of Early Differentiated-Type Gastric Cancers after Helicobacter pylori Eradication

    PubMed Central

    Horiguchi, Noriyuki; Tahara, Tomomitsu; Kawamura, Tomohiko; Okubo, Masaaki; Ishizuka, Takamitsu; Nakagawa, Yoshihito; Nagasaka, Mitsuo; Shibata, Tomoyuki; Ohmiya, Naoki

    2016-01-01

    Background. Gastric cancer is discovered even after successful eradication of H. pylori. We investigated clinic pathological features of early gastric cancers after H. pylori eradication. Methods. 51 early gastric cancers (EGCs) from 44 patients diagnosed after successful H. pylori eradication were included as eradication group. The clinic-pathological features were compared with that of 131 EGCs from 120 patients who did not have a history of H. pylori eradication (control group). Results. Compared with control group, clinic-pathological features of eradication group were characterized as depressed (p < 0.0001), reddish (p = 0.0001), and smaller (p = 0.0095) lesions, which was also confirmed in the comparison of six metachronous lesions diagnosed after initial ESD and subsequent successful H. pylori eradication. Prevalence of both SM2 (submucosal invasion greater than 500 μm) and unexpected SM2 cases tended to be higher in eradication group (p = 0.077, 0.0867, resp.). Prevalence of inconclusive diagnosis of gastric cancer during pretreatment biopsy was also higher in the same group (26.0% versus 1.6%, p < 0.0001). Conclusions. Informative clinic pathological features of EGC after H. pylori eradication are depressed, reddish appearances, which should be treated as a caution because histological diagnosis of cancerous tissue is sometimes difficult by endoscopic biopsy. PMID:27212944

  11. Clinical and Imaging Features of a Congenital Midline Cervical Cleft in a Neonate: A Rare Anomaly

    PubMed Central

    Bawa, Pritish; Ibrahim, Zachary; Amodio, John

    2015-01-01

    Congenital midline cervical cleft (CMCC) is a rare congenital anomaly. CMCC and its complications and treatment have been well described in ENT, dermatology, and pediatric surgery literature. However, to our knowledge, the imaging work-up has not been reported in the literature thus far. We present a case of CMCC in a neonate with description of clinical presentation and imaging features. PMID:26078904

  12. Clinical impact of molecular features in diffuse large B-cell lymphoma and follicular lymphoma.

    PubMed

    Pon, Julia R; Marra, Marco A

    2016-01-14

    Our understanding of the pathogenesis and heterogeneity of diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) has been dramatically enhanced by recent attempts to profile molecular features of these lymphomas. In this article, we discuss ways in which testing for molecular features may impact DLBCL and FL management if clinical trials are designed to incorporate such tests. Specifically, we discuss how distinguishing lymphomas on the basis of cell-of-origin subtypes or the presence of other molecular features is prognostically and therapeutically significant. Conversely, we discuss how the molecular similarities of DLBCL and FL have provided insight into the potential of both DLBCL and FL cases to respond to agents targeting alterations they have in common. Through these examples, we demonstrate how the translation of our understanding of cancer biology into improvements in patient outcomes depends on analyzing the molecular correlates of treatment outcomes in clinical trials and in routinely treated patients. PMID:26447189

  13. Cauda equina syndrome as the initial presenting clinical feature of medulloblastoma: a case report

    PubMed Central

    2012-01-01

    Introduction Medulloblastoma is one of the most common pediatric brain malignancies. The usual presenting clinical features are related to posterior fossa syndrome or/and hydrocephalus. Cauda equina syndrome is a very rare presentation for this disease. Case presentation We describe the case of a three-year-old boy with cauda equina syndrome as the initial presenting clinical feature for medulloblastoma. He was initially diagnosed as having a spinal tumor by magnetic resonance imaging scan. Subsequently, a cranial magnetic resonance imaging scan revealed a posterior fossa tumor with features of dissemination. He had substantial improvement after treatment. This case report is complemented by a literature review related to this unusual presentation. Conclusions Medulloblastoma primarily presenting with cauda equina syndrome is very rare. However, spinal drop metastasis should be considered in the pediatric age group to avoid suboptimal management. PMID:22620685

  14. Predicting Essential Genes and Proteins Based on Machine Learning and Network Topological Features: A Comprehensive Review

    PubMed Central

    Zhang, Xue; Acencio, Marcio Luis; Lemke, Ney

    2016-01-01

    Essential proteins/genes are indispensable to the survival or reproduction of an organism, and the deletion of such essential proteins will result in lethality or infertility. The identification of essential genes is very important not only for understanding the minimal requirements for survival of an organism, but also for finding human disease genes and new drug targets. Experimental methods for identifying essential genes are costly, time-consuming, and laborious. With the accumulation of sequenced genomes data and high-throughput experimental data, many computational methods for identifying essential proteins are proposed, which are useful complements to experimental methods. In this review, we show the state-of-the-art methods for identifying essential genes and proteins based on machine learning and network topological features, point out the progress and limitations of current methods, and discuss the challenges and directions for further research. PMID:27014079

  15. IFGFA: Identification of featured genes from genomic data using factor analysis.

    PubMed

    Fu, C H; Deng, S; Wu, J H; Wu, X Q; Fu, Z H; Yu, Z G

    2016-01-01

    In this study, a software tool (IFGFA) for identification of featured genes from gene expression data based on latent factor analysis was developed. Despite the availability of computational methods and statistical models appropriate for analyzing special genomic data, IFGFA provides a platform for predicting colon cancer-related genes and can be applied to other cancer types. The computational framework behind IFGFA is based on the well-established Bayesian factor and regression model and prior knowledge about the gene from OMIM. We validated the predicted genes by analyzing somatic mutations in patients. An interface was developed to enable users to run the computational framework efficiently through visual programming. IFGFA is executable in a Windows system and does not require other dependent software packages. This program can be freely downloaded at http://www.fupage.org/downloads/ifgfa.zip. PMID:27525867

  16. Chicken TAP genes differ from their human orthologues in locus organisation, size, sequence features and polymorphism.

    PubMed

    Walker, Brian A; van Hateren, Andrew; Milne, Sarah; Beck, Stephan; Kaufman, Jim

    2005-05-01

    We have previously shown that in the chicken major histocompatibility complex, the two transporters associated with antigen processing genes (TAP1 and TAP2) are located head to head between two classical class I genes. Here we show that the region between these two TAP genes has transcription factor-binding sites in common with class I gene promoters. The TAP genes are also up-regulated by interferon-gamma in a similar way to mammalian TAP genes and in a way that suggests they are both transcribed from a bi-directional promoter. The gene structures of TAP1 and TAP2 differ from that of human TAPs in that TAP1 has a truncated exon 1 and TAP2 has fused exons, resulting in a much smaller gene size. The truncation of TAP1 results in the loss of approximately 150 amino acids, which are thought to be involved in endoplasmic reticulum retention, heterodimer formation and tapasin binding, compared to human TAP1. Most of the protein sequence features involved in binding ATP are conserved, with two exceptions: chicken TAP1 has a glycine in the switch region where other TAPs have glutamine or histidine, and both chicken TAP genes have serines in the C motif where mammalian TAP2 has an alanine. Lastly, the chicken TAP genes are highly polymorphic, with at least as many TAP alleles as there are class I alleles, as seen by investigating nine inbred lines of chicken. The close proximity of the TAP genes to the class I genes and the high level of polymorphism may allow co-evolution of the genes, allowing TAP molecules to transport peptides specifically for the class I molecules of that haplotype. PMID:15900495

  17. How do clinical features help identify paediatric patients with fractures following blunt wrist trauma?

    PubMed Central

    Webster, A P; Goodacre, S; Walker, D; Burke, D

    2006-01-01

    Objective Wrist injuries are a common presentation to the emergency department (ED). There are no validated decision rules to help clinicians evaluate paediatric wrist trauma. This study aimed to identify which clinical features are diagnostically useful in deciding the need for a wrist radiograph, and then to develop a clinical decision rule. Methods This prospective cohort study was carried out in the ED of Sheffield Children's Hospital. Eligible patients were recruited if presenting within 72 hours following blunt wrist trauma. A standardised data collection form was completed for all patients. The outcome measure was the presence or absence of a fracture. Univariate analysis was performed with the χ2 test. Associated variables (p<0.2) were entered into a multivariate model. Classification and regression tree (CART) analysis was used to derive the clinical decision rule. Results In total, 227 patients were recruited and 106 children were diagnosed with fractures (47%). Of 10 clinical features analysed, six were found by univariate analysis to be associated with a fracture. CART analysis identified the presence of radial tenderness, focal swelling, or an abnormal supination/pronation as the best discriminatory features. Cross fold validation of this decision rule had a sensitivity of 99.1% (95% confidence interval 94.8% to 100%) and a specificity of 24.0% (17.2% to 32.3%). The radiography rate would be 87%. Conclusions Radial tenderness, focal swelling, and abnormal supination/pronation are associated with wrist fractures in children. The clinical decision rule derived from these features had a high sensitivity, but low specificity, and would not substantially alter our current radiography rate. The potential for a clinical decision rule for paediatric wrist trauma appears limited. PMID:16627835

  18. Stable feature selection for clinical prediction: exploiting ICD tree structure using Tree-Lasso.

    PubMed

    Kamkar, Iman; Gupta, Sunil Kumar; Phung, Dinh; Venkatesh, Svetha

    2015-02-01

    Modern healthcare is getting reshaped by growing Electronic Medical Records (EMR). Recently, these records have been shown of great value towards building clinical prediction models. In EMR data, patients' diseases and hospital interventions are captured through a set of diagnoses and procedures codes. These codes are usually represented in a tree form (e.g. ICD-10 tree) and the codes within a tree branch may be highly correlated. These codes can be used as features to build a prediction model and an appropriate feature selection can inform a clinician about important risk factors for a disease. Traditional feature selection methods (e.g. Information Gain, T-test, etc.) consider each variable independently and usually end up having a long feature list. Recently, Lasso and related l1-penalty based feature selection methods have become popular due to their joint feature selection property. However, Lasso is known to have problems of selecting one feature of many correlated features randomly. This hinders the clinicians to arrive at a stable feature set, which is crucial for clinical decision making process. In this paper, we solve this problem by using a recently proposed Tree-Lasso model. Since, the stability behavior of Tree-Lasso is not well understood, we study the stability behavior of Tree-Lasso and compare it with other feature selection methods. Using a synthetic and two real-world datasets (Cancer and Acute Myocardial Infarction), we show that Tree-Lasso based feature selection is significantly more stable than Lasso and comparable to other methods e.g. Information Gain, ReliefF and T-test. We further show that, using different types of classifiers such as logistic regression, naive Bayes, support vector machines, decision trees and Random Forest, the classification performance of Tree-Lasso is comparable to Lasso and better than other methods. Our result has implications in identifying stable risk factors for many healthcare problems and therefore can

  19. Socio-demographic, Clinical and Laboratory Features of Rotavirus Gastroenteritis in Children Treated in Pediatric Clinic

    PubMed Central

    Azemi, Mehmedali; Berisha, Majlinda; Ismaili-Jaha, Vlora; Kolgeci, Selim; Avdiu, Muharrem; Jakupi, Xhevat; Hoxha, Rina; Hoxha-Kamberi, Teuta

    2013-01-01

    Aim: The aim of work was presentation of several socio-demographic, clinical and laboratory characteristics of gastroenteritis caused by rotavirus. The examinees and methods: The examinees were children under the age of five years treated at the Pediatric Clinic due to acute gastroenteritis caused by rotavirus. Rotavirus is isolated by method chromatographic immunoassay by Cer Test Biotec. Results: From the total number of patients (850) suffering from acute gastroenteritis, feces test on bacteria, viruses. protozoa and fungi was positive in 425 (49.76%) cases. From this number the test on bacteria was positive in 248 (58.62%) cases, on viruses it was positive in 165 (39.0%), on protozoa in 9 (2.12%) cases and on fungi only one case. Rotavirus was the most frequent one in viral test, it was isolated in 142 (86.06%) cases, adenoviruses were found in 9 (5.45%) cases and noroviruses in only one case. The same feces sample that contained rotavirus and adenoviruses were isolated in five cases, whereas rotavirus with bacteria was isolated in the same feces sample in five cases. The biggest number of cases 62 (43.66%) were of the age 6-12 months, whereas the smallest number 10 (7.04%) cases were of the age 37-60 months. There were 76 (53.52%) of cases of male gender, from rural areas there were 81 (57.04%) cases and there were 58 (40.80%) cases during the summer period. Among the clinical symptoms the most prominent were diarrhea, vomiting, high temperature, whereas the different degree of dehydration were present in all cases (the most common one was moderate dehydration). The most frequent one was isonatremic dehydration in 91 (64.08%) cases, less frequent one was hypernatremic dehydration in 14 (9.85%) cases. The majority of cases (97.89%) had lower blood pH values, whereas 67 (47.17%) cases had pH values that varied from 7.16 -7.20 (curve peak), normal values were registered in only 3 (2.11%) cases. Urea values were increased in 45 (31.07%) cases (the maximum value

  20. The value of parsing as feature generation for gene mention recognition

    PubMed Central

    Smith, Larry H; Wilbur, W John

    2009-01-01

    We measured the extent to which information surrounding a base noun phrase reflects the presence of a gene name, and evaluated seven different parsers in their ability to provide information for that purpose. Using the GENETAG corpus as a gold standard, we performed machine learning to recognize from its context when a base noun phrase contained a gene name. Starting with the best lexical features, we assessed the gain of adding dependency or dependency-like relations from a full sentence parse. Features derived from parsers improved performance in this partial gene mention recognition task by a small but statistically significant amount. There were virtually no differences between parsers in these experiments. PMID:19345281

  1. A feature selection approach for identification of signature genes from SAGE data

    PubMed Central

    Barrera, Junior; Cesar, Roberto M; Humes, Carlos; Martins, David C; Patrão, Diogo FC; Silva, Paulo JS; Brentani, Helena

    2007-01-01

    Background One goal of gene expression profiling is to identify signature genes that robustly distinguish different types or grades of tumors. Several tumor classifiers based on expression profiling have been proposed using microarray technique. Due to important differences in the probabilistic models of microarray and SAGE technologies, it is important to develop suitable techniques to select specific genes from SAGE measurements. Results A new framework to select specific genes that distinguish different biological states based on the analysis of SAGE data is proposed. The new framework applies the bolstered error for the identification of strong genes that separate the biological states in a feature space defined by the gene expression of a training set. Credibility intervals defined from a probabilistic model of SAGE measurements are used to identify the genes that distinguish the different states with more reliability among all gene groups selected by the strong genes method. A score taking into account the credibility and the bolstered error values in order to rank the groups of considered genes is proposed. Results obtained using SAGE data from gliomas are presented, thus corroborating the introduced methodology. Conclusion The model representing counting data, such as SAGE, provides additional statistical information that allows a more robust analysis. The additional statistical information provided by the probabilistic model is incorporated in the methodology described in the paper. The introduced method is suitable to identify signature genes that lead to a good separation of the biological states using SAGE and may be adapted for other counting methods such as Massive Parallel Signature Sequencing (MPSS) or the recent Sequencing-By-Synthesis (SBS) technique. Some of such genes identified by the proposed method may be useful to generate classifiers. PMID:17519038

  2. Magnetic resonance imaging features of Great Danes with and without clinical signs of cervical spondylomyelopathy

    PubMed Central

    Martin-Vaquero, Paula; da Costa, Ronaldo C.

    2014-01-01

    Objective To characterize and compare the MRI morphological features of the cervical vertebral column of Great Danes with and without clinical signs of cervical spondylomyelopathy (CSM). Design Prospective cohort study. Animals 30 Great Danes (15 clinically normal and 15 CSM-affected). Procedures All dogs underwent MRI of the cervical vertebral column (C2–3 through T1–2). Features evaluated included sites of subarachnoid space compression, spinal cord compression, or both; degree, cause, and direction of compression; MRI signal changes of the spinal cord; articular process (facet) joint characteristics; internal vertebral venous plexus visibility; and presence of extradural synovial cysts as well as presence and degree of intervertebral disk degeneration and foraminal stenosis. Results Clinically normal and CSM-affected dogs had 11 and 61 compressive sites, respectively, detected with MRI. All CSM-affected dogs had ≥ 1 site of spinal cord compression. No signal changes were observed in spinal cords of normal dogs, whereas 14 sites of hyperintensity were found in 9 CSM-affected dogs. Foraminal stenosis was present in 11 clinically normal and all CSM-affected dogs. The number of stenotic foraminal sites was significantly greater in the CSM-affected group, and severe stenosis appeared to be more common in this group than in the clinically normal group. Significant differences were identified between clinically normal and CSM-affected dogs with regard to amount of synovial fluid evident, regularity of articular surfaces, degree of articular process joint proliferation, and internal vertebral venous plexus visibility. Conclusions and Clinical Relevance Abnormalities were detected with MRI in several clinically normal Great Danes. Severe spinal cord compression, number of stenotic foraminal sites, and signal changes within the spinal cord distinguished CSM-affected from clinically normal Great Danes. PMID:25075822

  3. DNA methylation profiling identifies two splenic marginal zone lymphoma subgroups with different clinical and genetic features

    PubMed Central

    Arribas, Alberto J.; Rinaldi, Andrea; Mensah, Afua A.; Kwee, Ivo; Cascione, Luciano; Robles, Eloy F.; Martinez-Climent, Jose A.; Oscier, David; Arcaini, Luca; Baldini, Luca; Marasca, Roberto; Thieblemont, Catherine; Briere, Josette; Forconi, Francesco; Zamò, Alberto; Bonifacio, Massimiliano; Mollejo, Manuela; Facchetti, Fabio; Dirnhofer, Stephan; Ponzoni, Maurilio; Bhagat, Govind; Piris, Miguel A.; Gaidano, Gianluca; Zucca, Emanuele; Rossi, Davide

    2015-01-01

    Splenic marginal zone lymphoma is a rare lymphoma. Loss of 7q31 and somatic mutations affecting the NOTCH2 and KLF2 genes are the commonest genomic aberrations. Epigenetic changes can be pharmacologically reverted; therefore, identification of groups of patients with specific epigenomic alterations might have therapeutic relevance. Here we integrated genome-wide DNA-promoter methylation profiling with gene expression profiling, and clinical and biological variables. An unsupervised clustering analysis of a test series of 98 samples identified 2 clusters with different degrees of promoter methylation. The cluster comprising samples with higher-promoter methylation (High-M) had a poorer overall survival compared with the lower (Low-M) cluster. The prognostic relevance of the High-M phenotype was confirmed in an independent validation set of 36 patients. In the whole series, the High-M phenotype was associated with IGHV1-02 usage, mutations of NOTCH2 gene, 7q31-32 loss, and histologic transformation. In the High-M set, a number of tumor-suppressor genes were methylated and repressed. PRC2 subunit genes and several prosurvival lymphoma genes were unmethylated and overexpressed. A model based on the methylation of 3 genes (CACNB2, HTRA1, KLF4) identified a poorer-outcome patient subset. Exposure of splenic marginal zone lymphoma cell lines to a demethylating agent caused partial reversion of the High-M phenotype and inhibition of proliferation. PMID:25612624

  4. DNA methylation profiling identifies two splenic marginal zone lymphoma subgroups with different clinical and genetic features.

    PubMed

    Arribas, Alberto J; Rinaldi, Andrea; Mensah, Afua A; Kwee, Ivo; Cascione, Luciano; Robles, Eloy F; Martinez-Climent, Jose A; Oscier, David; Arcaini, Luca; Baldini, Luca; Marasca, Roberto; Thieblemont, Catherine; Briere, Josette; Forconi, Francesco; Zamò, Alberto; Bonifacio, Massimiliano; Mollejo, Manuela; Facchetti, Fabio; Dirnhofer, Stephan; Ponzoni, Maurilio; Bhagat, Govind; Piris, Miguel A; Gaidano, Gianluca; Zucca, Emanuele; Rossi, Davide; Bertoni, Francesco

    2015-03-19

    Splenic marginal zone lymphoma is a rare lymphoma. Loss of 7q31 and somatic mutations affecting the NOTCH2 and KLF2 genes are the commonest genomic aberrations. Epigenetic changes can be pharmacologically reverted; therefore, identification of groups of patients with specific epigenomic alterations might have therapeutic relevance. Here we integrated genome-wide DNA-promoter methylation profiling with gene expression profiling, and clinical and biological variables. An unsupervised clustering analysis of a test series of 98 samples identified 2 clusters with different degrees of promoter methylation. The cluster comprising samples with higher-promoter methylation (High-M) had a poorer overall survival compared with the lower (Low-M) cluster. The prognostic relevance of the High-M phenotype was confirmed in an independent validation set of 36 patients. In the whole series, the High-M phenotype was associated with IGHV1-02 usage, mutations of NOTCH2 gene, 7q31-32 loss, and histologic transformation. In the High-M set, a number of tumor-suppressor genes were methylated and repressed. PRC2 subunit genes and several prosurvival lymphoma genes were unmethylated and overexpressed. A model based on the methylation of 3 genes (CACNB2, HTRA1, KLF4) identified a poorer-outcome patient subset. Exposure of splenic marginal zone lymphoma cell lines to a demethylating agent caused partial reversion of the High-M phenotype and inhibition of proliferation. PMID:25612624

  5. Clinical Features of 78 Adults With 22q11 Deletion Syndrome

    PubMed Central

    Bassett, Anne S.; Chow, Eva W.C.; Husted, Janice; Weksberg, Rosanna; Caluseriu, Oana; Webb, Gary D.; Gatzoulis, Michael A.

    2011-01-01

    22q11 Deletion Syndrome (22q11DS) is a common microdeletion syndrome with multisystem expression. Phenotypic features vary with age, ascertainment, and assessment. We systematically assessed 78 adults (36 M, 42 F; mean age 31.5, SD 10.5 years) with a 22q11.2 deletion ascertained through an adult congenital cardiac clinic (n = 35), psychiatric-related sources (n = 39), or as affected parents of subjects (n = 4). We recorded the lifetime prevalence of features requiring attention, with 95% confidence intervals (CI) not overlapping zero. Subtle learning difficulties, hypernasality and facial gestalt were not included. We investigated ascertainment effects using non-overlapping subgroups ascertained with tetralogy of Fallot (n = 31) or schizophrenia (n = 31). Forty-three features met inclusion criteria and were present in 5% or more patients, including several of later onset (e.g., hypothyroidism, cholelithiasis). Number of features per patient (median 9, range 3–22) correlated with hospitalizations (P=0.0002) and, when congenital features were excluded, with age (P=0.02). Adjusting for ascertainment, 25.8% (95% CI, 9.5–42.1%) of patients had cardiac anomalies and 22.6% (95% CI, 7.0–38.2%) had schizophrenia. Ascertainment subgroups were otherwise similar in median number and prevalence of features. Non-characteristic features are common in 22q11DS. Adjusting for ascertainment effects is important. Many treatable conditions may be anticipated and features may accumulate over time. The results have implications for clinical assessment and management, genetic counseling and research into pathophysiological mechanisms. PMID:16208694

  6. Melanocytic nevi with special features: clinical-dermoscopic and reflectance confocal microscopic-findings.

    PubMed

    Larre Borges, A; Zalaudek, I; Longo, C; Dufrechou, L; Argenziano, G; Lallas, A; Piana, S; Moscarella, E

    2014-07-01

    Histopathology is considered the 'gold' standard for the diagnosis and classification of melanocytic nevi, but the widespread use of in vivo diagnostic technologies such as dermoscopy and reflectance confocal microscopy (RCM), has enriched profoundly the knowledge regarding the morphological variability in nevi. This is because most morphological observations made via these in vivo tools are closely correlated with features seen in histopathology. Dermoscopy has allowed for a more detailed classification of nevi. As such, dermoscopy identifies four main morphologic groups (i.e. globular, reticular, starburst and structureless blue nevi), one group of nevi located at special body sites (i.e. face, acral, nail) and one group of nevi with special features. This latter category consists of nevi of the former categories, which are typified by peculiar clinical-histopathological findings. They can be subdivided into 'melanoma simulators' including combined nevi, recurrent nevi and sclerosing nevus with pseudomelanomatous features, 'targetoid' nevi (i.e. halo, cockade, irritated targetoid haemosiderotic and eczematous nevus) and uncommon histopathological variants such as desmoplastic, white dysplastic or ballon cell nevus. While the dermoscopic and RCM patterns of the former categories have been studied in detail, little is currently known about the clinical morphology of the heterogeneous group of 'special' nevi. In this article, we describe the clinical, dermoscopic and RCM features of 'special' nevi and review the current literature on this group of melanocytic proliferations. PMID:24171788

  7. Clinical and Molecular Cytogenetic Characterisation of Children with Developmental Delay and Dysmorphic Features

    PubMed Central

    BERTOK, Sara; ŽERJAV TANŠEK, Mojca; KOTNIK, Primož; BATTELINO, Tadej; VOLK, Marija; PECILE, Vanna; CLEVA, Lisa; GASPARINI, Paolo; KOVAČ, Jernej; HOVNIK, Tinka

    2015-01-01

    Introduction Developmental delay and dysmorphic features affect 1 – 3 % of paediatric population. In the last few years molecular cytogenetic high resolution techniques (comparative genomic hybridization arrays and single-nucleotide polymorphism arrays) have been proven to be a first-tier choice for clinical diagnostics of developmental delay and dysmorphic features. Methods and results In the present article we describe the clinical advantages of molecular cytogenetic approach (comparative genomic hybridization arrays and single nucleotide polymorphism arrays) in the diagnostic procedure of two children with developmental delay, dysmorphic features and additional morphological phenotypes. Additionally, we demonstrate the necessity of fluorescent in situ hybridization utilisation to identify the localisation and underlying mechanism of detected chromosomal rearrangement. Conclusions Two types of chromosomal abnormalities were identified and confirmed using different molecular genetic approaches. Comparative genomic hybridization arrays and single nucleotide polymorphism arrays are hereby presented as important methods to identify chromosomal imbalances in patients with developmental delay and dysmorphic features. We emphasize the importance of molecular genetic testing in patients’ parents for the demonstration of the origin and clinical importance of the aberrations prior determined in the patients. The results obtained using molecular cytogenetic high resolution techniques methods are the cornerstone for proper genetic counselling to the affected families.

  8. Genetic Acquisition of NDM Gene Offers Sustainability among Clinical Isolates of Pseudomonas aeruginosa in Clinical Settings

    PubMed Central

    Mishra, Shweta; Upadhyay, Supriya; Sen, Malay Ranjan; Maurya, Anand Prakash; Choudhury, Debarati; Bhattacharjee, Amitabha

    2015-01-01

    New Delhi metallo β-lactamases are one of the most significant emerging resistance determinants towards carbapenem drugs. Their persistence and adaptability often depends on their genetic environment and linkage. This study reports a unique and novel arrangement of blaNDM-1 gene within clinical isolates of Pseudomonas aeruginosa from a tertiary referral hospital in north India. Three NDM positive clonally unrelated clinical isolates of P. aeruginosa were recovered from hospital patients. Association of integron with blaNDM-1 and presence of gene cassettes were assessed by PCR. Genetic linkage of NDM gene with ISAba125 was determined and in negative cases linkage in upstream region was mapped by inverse PCR. In which only one isolate’s NDM gene was linked with ISAba125 for mobility, while other two reveals new genetic arrangement and found to be inserted within DNA directed RNA polymerase gene of the host genome detected by inverse PCR followed by sequencing analysis. In continuation significance of this novel linkage was further analyzed wherein promoter site detected by Softberry BPROM software and activity were assessed by cloning succeeding semi-quantitative RT-PCR indicating the higher expression level of NDM gene. This study concluded out that the unique genetic makeup of NDM gene with DNA-dependent-RNA-polymerase favours adaptability to the host in hospital environment against huge antibiotic pressure. PMID:25635921

  9. Genetic acquisition of NDM gene offers sustainability among clinical isolates of Pseudomonas aeruginosa in clinical settings.

    PubMed

    Mishra, Shweta; Upadhyay, Supriya; Sen, Malay Ranjan; Maurya, Anand Prakash; Choudhury, Debarati; Bhattacharjee, Amitabha

    2015-01-01

    New Delhi metallo β-lactamases are one of the most significant emerging resistance determinants towards carbapenem drugs. Their persistence and adaptability often depends on their genetic environment and linkage. This study reports a unique and novel arrangement of blaNDM-1 gene within clinical isolates of Pseudomonas aeruginosa from a tertiary referral hospital in north India. Three NDM positive clonally unrelated clinical isolates of P. aeruginosa were recovered from hospital patients. Association of integron with blaNDM-1 and presence of gene cassettes were assessed by PCR. Genetic linkage of NDM gene with ISAba125 was determined and in negative cases linkage in upstream region was mapped by inverse PCR. In which only one isolate's NDM gene was linked with ISAba125 for mobility, while other two reveals new genetic arrangement and found to be inserted within DNA directed RNA polymerase gene of the host genome detected by inverse PCR followed by sequencing analysis. In continuation significance of this novel linkage was further analyzed wherein promoter site detected by Softberry BPROM software and activity were assessed by cloning succeeding semi-quantitative RT-PCR indicating the higher expression level of NDM gene. This study concluded out that the unique genetic makeup of NDM gene with DNA-dependent-RNA-polymerase favours adaptability to the host in hospital environment against huge antibiotic pressure. PMID:25635921

  10. Computational phenotype discovery using unsupervised feature learning over noisy, sparse, and irregular clinical data.

    PubMed

    Lasko, Thomas A; Denny, Joshua C; Levy, Mia A

    2013-01-01

    Inferring precise phenotypic patterns from population-scale clinical data is a core computational task in the development of precision, personalized medicine. The traditional approach uses supervised learning, in which an expert designates which patterns to look for (by specifying the learning task and the class labels), and where to look for them (by specifying the input variables). While appropriate for individual tasks, this approach scales poorly and misses the patterns that we don't think to look for. Unsupervised feature learning overcomes these limitations by identifying patterns (or features) that collectively form a compact and expressive representation of the source data, with no need for expert input or labeled examples. Its rising popularity is driven by new deep learning methods, which have produced high-profile successes on difficult standardized problems of object recognition in images. Here we introduce its use for phenotype discovery in clinical data. This use is challenging because the largest source of clinical data - Electronic Medical Records - typically contains noisy, sparse, and irregularly timed observations, rendering them poor substrates for deep learning methods. Our approach couples dirty clinical data to deep learning architecture via longitudinal probability densities inferred using Gaussian process regression. From episodic, longitudinal sequences of serum uric acid measurements in 4368 individuals we produced continuous phenotypic features that suggest multiple population subtypes, and that accurately distinguished (0.97 AUC) the uric-acid signatures of gout vs. acute leukemia despite not being optimized for the task. The unsupervised features were as accurate as gold-standard features engineered by an expert with complete knowledge of the domain, the classification task, and the class labels. Our findings demonstrate the potential for achieving computational phenotype discovery at population scale. We expect such data

  11. Computational Phenotype Discovery Using Unsupervised Feature Learning over Noisy, Sparse, and Irregular Clinical Data

    PubMed Central

    Lasko, Thomas A.; Denny, Joshua C.; Levy, Mia A.

    2013-01-01

    Inferring precise phenotypic patterns from population-scale clinical data is a core computational task in the development of precision, personalized medicine. The traditional approach uses supervised learning, in which an expert designates which patterns to look for (by specifying the learning task and the class labels), and where to look for them (by specifying the input variables). While appropriate for individual tasks, this approach scales poorly and misses the patterns that we don’t think to look for. Unsupervised feature learning overcomes these limitations by identifying patterns (or features) that collectively form a compact and expressive representation of the source data, with no need for expert input or labeled examples. Its rising popularity is driven by new deep learning methods, which have produced high-profile successes on difficult standardized problems of object recognition in images. Here we introduce its use for phenotype discovery in clinical data. This use is challenging because the largest source of clinical data – Electronic Medical Records – typically contains noisy, sparse, and irregularly timed observations, rendering them poor substrates for deep learning methods. Our approach couples dirty clinical data to deep learning architecture via longitudinal probability densities inferred using Gaussian process regression. From episodic, longitudinal sequences of serum uric acid measurements in 4368 individuals we produced continuous phenotypic features that suggest multiple population subtypes, and that accurately distinguished (0.97 AUC) the uric-acid signatures of gout vs. acute leukemia despite not being optimized for the task. The unsupervised features were as accurate as gold-standard features engineered by an expert with complete knowledge of the domain, the classification task, and the class labels. Our findings demonstrate the potential for achieving computational phenotype discovery at population scale. We expect such data

  12. Recurrent Wernicke's Encephalopathy in a 16-Year-Old Girl with Atypical Clinical and Radiological Features

    PubMed Central

    Lamdhade, S.; Almulla, A.; Alroughani, R.

    2014-01-01

    Background. Wernicke's Encephalopathy (WE) is a clinical diagnosis with serious neurological consequences. Its occurrence is underestimated in nonalcoholics and is uncommon in adolescents. We aim to draw the attention to a rare case, which had additional clinical and radiological features. Case. A 16-year-old girl presented with three-week history of vomiting secondary to intestinal obstruction. She developed diplopia soon after hospitalization. Neurological evaluation revealed restriction of bilateral lateral recti with horizontal nystagmus, and bilateral limb dysmetria. Brain MRI was normal. She had prompt improvement to thiamine. Four months later, she presented with headache, bilateral severe deafness, and tinnitus. Clinically, she had severe sensorineural hearing loss, bilateral lateral recti paresis, and gait ataxia. CT head showed bilateral caudate nucleus hypodensities. MRI brain revealed gadolinium enhancement of mamillary bodies and vermis. She had significant improvement after IV thiamine. Headache completely resolved while the ocular movements, hearing, and tinnitus improved partially in 72 hours. Conclusions. Recurrent WE in adolescence is uncommon. Headache, tinnitus, and deafness are rare clinical features. Although MRI study shows typical features of WE, the presence of bilateral caudate nuclei hypodensities on CT scan is uncommon. Prompt treatment with thiamine is warranted in suspected cases to prevent permanent neurological sequelae. PMID:24790762

  13. Hollow organ abdominal ischemia, part II: clinical features, etiology, imaging findings and management.

    PubMed

    Ricci, Zina J; Mazzariol, Fernanda S; Kaul, Bindu; Oh, Sarah K; Chernyak, Victoria; Flusberg, Milana; Stein, Marjorie W; Rozenblit, Alla M

    2016-01-01

    Acute hollow organ ischemia commonly presents with acute pain prompting radiologic evaluation and almost always requires urgent treatment. Despite different risk factors and anatomic differences, ischemia is commonly due to low flow states but can also be due to arterial and venous occlusion. Radiologic diagnosis is critical as many present with nonspecific symptoms. Contrast-enhanced computed tomography (CT) is the modality of choice. Magnetic resonance imaging (MRI) is preferred in suspected appendicitis in pregnant patients and is superior in biliary necrosis. This article provides a pictorial review of the CT/MRI features of hollow abdominal organ ischemia while highlighting key clinical features, pathogenesis, and management. PMID:27317221

  14. Clinical Features and Histology of Apolipoprotein L1-Associated Nephropathy in the FSGS Clinical Trial

    PubMed Central

    Winkler, Cheryl A.; Zhao, Xiongce; Radeva, Milena K.; Gassman, Jennifer J.; D’Agati, Vivette D.; Nast, Cynthia C.; Wei, Changli; Reiser, Jochen; Guay-Woodford, Lisa M.; Pollak, Martin R.; Hildebrandt, Friedhelm; Moxey-Mims, Marva; Gipson, Debbie S.; Trachtman, Howard; Friedman, Aaron L.; Kaskel, Frederick J.

    2015-01-01

    Genetic variants in apolipoprotein L1 (APOL1) confer risk for kidney disease. We sought to better define the phenotype of APOL1-associated nephropathy. The FSGS Clinical Trial involved 138 children and young adults who were randomized to cyclosporin or mycophenolate mofetil plus pulse oral dexamethasone with a primary outcome of proteinuria remission. DNA was available from 94 subjects who were genotyped for APOL1 renal risk variants, with two risk alleles comprising the risk genotype. Two APOL1 risk alleles were present in 27 subjects, of whom four subjects did not self-identify as African American, and 23 of 32 (72%) self-identified African Americans. Individuals with the APOL1 risk genotype tended to present at an older age and had significantly lower baseline eGFR, more segmental glomerulosclerosis and total glomerulosclerosis, and more tubular atrophy/interstitial fibrosis. There were differences in renal histology, particularly more collapsing variants in those with the risk genotype (P=0.02), although this association was confounded by age. APOL1 risk genotype did not affect response to either treatment regimen. Individuals with the risk genotype were more likely to progress to ESRD (P<0.01). In conclusion, APOL1 risk genotypes are common in African-American subjects with primary FSGS and may also be present in individuals who do not self-identify as African American. APOL1 risk status is associated with lower kidney function, more glomerulosclerosis and interstitial fibrosis, and greater propensity to progress to ESRD. The APOL1 risk genotype did not influence proteinuria responses to cyclosporin or mycophenolate mofetil/dexamethasone. PMID:25573908

  15. Clinical Features and Histology of Apolipoprotein L1-Associated Nephropathy in the FSGS Clinical Trial.

    PubMed

    Kopp, Jeffrey B; Winkler, Cheryl A; Zhao, Xiongce; Radeva, Milena K; Gassman, Jennifer J; D'Agati, Vivette D; Nast, Cynthia C; Wei, Changli; Reiser, Jochen; Guay-Woodford, Lisa M; Pollak, Martin R; Hildebrandt, Friedhelm; Moxey-Mims, Marva; Gipson, Debbie S; Trachtman, Howard; Friedman, Aaron L; Kaskel, Frederick J

    2015-06-01

    Genetic variants in apolipoprotein L1 (APOL1) confer risk for kidney disease. We sought to better define the phenotype of APOL1-associated nephropathy. The FSGS Clinical Trial involved 138 children and young adults who were randomized to cyclosporin or mycophenolate mofetil plus pulse oral dexamethasone with a primary outcome of proteinuria remission. DNA was available from 94 subjects who were genotyped for APOL1 renal risk variants, with two risk alleles comprising the risk genotype. Two APOL1 risk alleles were present in 27 subjects, of whom four subjects did not self-identify as African American, and 23 of 32 (72%) self-identified African Americans. Individuals with the APOL1 risk genotype tended to present at an older age and had significantly lower baseline eGFR, more segmental glomerulosclerosis and total glomerulosclerosis, and more tubular atrophy/interstitial fibrosis. There were differences in renal histology, particularly more collapsing variants in those with the risk genotype (P=0.02), although this association was confounded by age. APOL1 risk genotype did not affect response to either treatment regimen. Individuals with the risk genotype were more likely to progress to ESRD (P<0.01). In conclusion, APOL1 risk genotypes are common in African-American subjects with primary FSGS and may also be present in individuals who do not self-identify as African American. APOL1 risk status is associated with lower kidney function, more glomerulosclerosis and interstitial fibrosis, and greater propensity to progress to ESRD. The APOL1 risk genotype did not influence proteinuria responses to cyclosporin or mycophenolate mofetil/dexamethasone. PMID:25573908

  16. Inflammatory features of pancreatic cancer highlighted by monocytes/macrophages and CD4+ T cells with clinical impact

    PubMed Central

    Komura, Takuya; Sakai, Yoshio; Harada, Kenichi; Kawaguchi, Kazunori; Takabatake, Hisashi; Kitagawa, Hirohisa; Wada, Takashi; Honda, Masao; Ohta, Tetsuo; Nakanuma, Yasuni; Kaneko, Shuichi

    2015-01-01

    Pancreatic ductal adenocarcinoma (PDAC) is among the most fatal of malignancies with an extremely poor prognosis. The objectives of this study were to provide a detailed understanding of PDAC pathophysiology in view of the host immune response. We examined the PDAC tissues, sera, and peripheral blood cells of PDAC patients using immunohistochemical staining, the measurement of cytokine/chemokine concentrations, gene expression analysis, and flow cytometry. The PDAC tissues were infiltrated by macrophages, especially CD33+CD163+ M2 macrophages and CD4+ T cells that concomitantly express programmed cell death-1 (PD-1). Concentrations of interleukin (IL)-6, IL-7, IL-15, monocyte chemotactic protein-1, and interferon-γ-inducible protein-1 in the sera of PDAC patients were significantly elevated. The gene expression profile of CD14+ monocytes and CD4+ T cells was discernible between PDAC patients and healthy volunteers, and the differentially expressed genes were related to activated inflammation. Intriguingly, PD-1 was significantly upregulated in the peripheral blood CD4+ T cells of PDAC patients. Correspondingly, the frequency of CD4+PD-1+ T cells was increased in the peripheral blood cells of PDAC patients, and this increase correlated to chemotherapy resistance. In conclusion, inflammatory conditions in both PDAC tissue and peripheral blood cells in PDAC patients were prominent, highlighting monocytes/macrophages as well as CD4+ T cells with influence of the clinical prognosis. We examined the inflammatory features of PDAC patients using the PDAC tissues, sera, and peripheral blood by immunohistochemical staining, measurement of cytokines/chemokines, gene expression analysis, and flow cytometry. We foundg that monocyte/macrophage cells and CD4+ T cells were highlighted immune-mediating cells in local cancer tissue as well as in peripheral blood of PDAC patients, among which the important subfraction with clinical impact influencing PDAC prognosis by chemotherapy

  17. "Orbiting around" the orbital myositis: clinical features, differential diagnosis and therapy.

    PubMed

    Montagnese, F; Wenninger, S; Schoser, B

    2016-04-01

    Orbital myositis (OM) is a rare disease whose clinical heterogeneity and different treatment options represent a diagnostic and therapeutic challenge. We aim to review the state of knowledge on OM, also describing a cohort of patients diagnosed in our centre, to highlight some remarkable clinical features. A literature review was conducted in PubMed and Medline databases. The herein described cohort is composed of seven OM patients, diagnosed according to clinical, laboratory and neuroradiological features, whose clinical data were retrospectively analysed. OM is a non-infectious, inflammatory process primarily involving extraocular eye-muscles. It typically presents as an acute to sub-acute, painful ophthalmoplegia with signs of ocular inflammation, but atypical cases without pain or with a chronic progression have been described. The wide range of OM mimicking diseases make a prompt diagnosis challenging but orbit MRI provides valuable clues for differential diagnosis. Timely treatment is greatly important as OM promptly responds to steroids; nevertheless, partial recovery or relapses often occur. In refractory, recurrent or steroid-intolerant cases other therapeutic options (radiotherapy, immunosuppressants, immunoglobulins) can be adopted, but the most effective therapeutic management is yet to be established. In this review, we provide a detailed clinical description of OM, considering the main differential diagnoses and suggesting the most useful investigations. In light of the currently available data on therapy efficacy, we propose a therapeutic algorithm that may guide neurologists in OM patients' management. PMID:26477021

  18. Increased functional protein expression using nucleotide sequence features enriched in highly expressed genes in zebrafish

    PubMed Central

    Horstick, Eric J.; Jordan, Diana C.; Bergeron, Sadie A.; Tabor, Kathryn M.; Serpe, Mihaela; Feldman, Benjamin; Burgess, Harold A.

    2015-01-01

    Many genetic manipulations are limited by difficulty in obtaining adequate levels of protein expression. Bioinformatic and experimental studies have identified nucleotide sequence features that may increase expression, however it is difficult to assess the relative influence of these features. Zebrafish embryos are rapidly injected with calibrated doses of mRNA, enabling the effects of multiple sequence changes to be compared in vivo. Using RNAseq and microarray data, we identified a set of genes that are highly expressed in zebrafish embryos and systematically analyzed for enrichment of sequence features correlated with levels of protein expression. We then tested enriched features by embryo microinjection and functional tests of multiple protein reporters. Codon selection, releasing factor recognition sequence and specific introns and 3′ untranslated regions each increased protein expression between 1.5- and 3-fold. These results suggested principles for increasing protein yield in zebrafish through biomolecular engineering. We implemented these principles for rational gene design in software for codon selection (CodonZ) and plasmid vectors incorporating the most active non-coding elements. Rational gene design thus significantly boosts expression in zebrafish, and a similar approach will likely elevate expression in other animal models. PMID:25628360

  19. CT findings and clinical features of pancreatic hemolymphangioma: a case report and review of the literature.

    PubMed

    Pan, Liang; Jian-bo, Gao; Javier, Pullas Tapia Gonzalo

    2015-01-01

    Pancreatic hemolymphangioma is a very rare benign tumor. There were only 10 reports of this disease until June 2014.The aim of the present study was to describe a hemolymphangioma in the neck and body of the pancreas in a 57-year-old woman.The method used in the present study consists of description of the clinical history, image lab features, and pathological result.The patient complained of a 10-day history of epigastric discomfort. Abdominal computed tomography (CT) showed a cystic-solid tumor with an irregular shape, in the neck and body of the pancreas. The tumoral cystic wall and its internal division could be seen intensified on contrast-enhanced CT images compared with those on precontrast images. The pathological examination confirmed the diagnosis.The clinical feature of pancreatic hemolymphangioma includes a lack of specificity. The CT appearance combined with age and sex may be useful in making an early diagnosis. PMID:25621699

  20. Glucose transporter 1 deficiency syndrome and hemiplegic migraines as a dominant presenting clinical feature.

    PubMed

    Mohammad, Shekeeb S; Coman, David; Calvert, Sophie

    2014-12-01

    Glucose transporter 1 deficiency syndrome (OMIM 606777) is a treatable epileptic encephalopathy caused by mutations in the SLC2A1 gene (OMIM 138140) causing impaired glucose transport into the brain. The classical phenotype is associated with seizures, developmental delay, ataxia and spasticity; however, milder phenotypes are emerging. We describe an 8-year-old boy with glucose transporter 1 deficiency syndrome whose clinical presentation was dominated by hemiplegic migraines that resolved with institution of a modified Atkins diet. PMID:25440161

  1. Quantitative modeling of gene expression using DNA shape features of binding sites.

    PubMed

    Peng, Pei-Chen; Sinha, Saurabh

    2016-07-27

    Prediction of gene expression levels driven by regulatory sequences is pivotal in genomic biology. A major focus in transcriptional regulation is sequence-to-expression modeling, which interprets the enhancer sequence based on transcription factor concentrations and DNA binding specificities and predicts precise gene expression levels in varying cellular contexts. Such models largely rely on the position weight matrix (PWM) model for DNA binding, and the effect of alternative models based on DNA shape remains unexplored. Here, we propose a statistical thermodynamics model of gene expression using DNA shape features of binding sites. We used rigorous methods to evaluate the fits of expression readouts of 37 enhancers regulating spatial gene expression patterns in Drosophila embryo, and show that DNA shape-based models perform arguably better than PWM-based models. We also observed DNA shape captures information complimentary to the PWM, in a way that is useful for expression modeling. Furthermore, we tested if combining shape and PWM-based features provides better predictions than using either binding model alone. Our work demonstrates that the increasingly popular DNA-binding models based on local DNA shape can be useful in sequence-to-expression modeling. It also provides a framework for future studies to predict gene expression better than with PWM models alone. PMID:27257066

  2. Basal Cell Carcinoma: Pathogenesis, Epidemiology, Clinical Features, Diagnosis, Histopathology, and Management

    PubMed Central

    Marzuka, Alexander G.; Book, Samuel E.

    2015-01-01

    Basal cell carcinoma (BCC) is the most common malignancy. Exposure to sunlight is the most important risk factor. Most, if not all, cases of BCC demonstrate overactive Hedgehog signaling. A variety of treatment modalities exist and are selected based on recurrence risk, importance of tissue preservation, patient preference, and extent of disease. The pathogenesis, epidemiology, clinical features, diagnosis, histopathology, and management of BCC will be discussed in this review. PMID:26029015

  3. A case of asymptomatic pancytopenia with clinical features of hemolysis as a presentation of pernicious anemia.

    PubMed

    Kollipara, Venkateswara K; Brine, Patrick L; Gemmel, David; Ingnam, Sisham

    2016-01-01

    Pernicious anemia is an autoimmune disease with a variety of clinical presentations. We describe a case of pernicious anemia presenting with pancytopenia with hemolytic features. Further workup revealed very low vitamin B12 levels and elevated methylmalonic acid. It is important for a general internist to identify pernicious anemia as one of the cause of pancytopenia and hemolytic anemia to avoid extensive workup. Pernicious anemia can present strictly with hematological abnormalities without neurological problems or vice versa as in our case. PMID:27609735

  4. Comparison of clinical, radionuclide, and radiographic features of osteoarthritis of the hands.

    PubMed Central

    Macfarlane, D G; Buckland-Wright, J C; Emery, P; Fogelman, I; Clark, B; Lynch, J

    1991-01-01

    Simultaneous clinical, scintigraphic, and macroradiographic assessments were carried out on 32 patients with hand osteoarthritis and the results at entry and one year reported. The presence and growth of osteophyte correlated with symptoms and a positive scan. The scan did not detect the radiographic features of juxta-articular radiolucencies, subchondral sclerosis, or cartilage thinning. Osteophytes, particularly when fast growing, produce pain, a 'hot' scan, and may predict disintegration of joint architecture. PMID:1929584

  5. Feature weight estimation for gene selection: a local hyperlinear learning approach

    PubMed Central

    2014-01-01

    Background Modeling high-dimensional data involving thousands of variables is particularly important for gene expression profiling experiments, nevertheless,it remains a challenging task. One of the challenges is to implement an effective method for selecting a small set of relevant genes, buried in high-dimensional irrelevant noises. RELIEF is a popular and widely used approach for feature selection owing to its low computational cost and high accuracy. However, RELIEF based methods suffer from instability, especially in the presence of noisy and/or high-dimensional outliers. Results We propose an innovative feature weighting algorithm, called LHR, to select informative genes from highly noisy data. LHR is based on RELIEF for feature weighting using classical margin maximization. The key idea of LHR is to estimate the feature weights through local approximation rather than global measurement, which is typically used in existing methods. The weights obtained by our method are very robust in terms of degradation of noisy features, even those with vast dimensions. To demonstrate the performance of our method, extensive experiments involving classification tests have been carried out on both synthetic and real microarray benchmark datasets by combining the proposed technique with standard classifiers, including the support vector machine (SVM), k-nearest neighbor (KNN), hyperplane k-nearest neighbor (HKNN), linear discriminant analysis (LDA) and naive Bayes (NB). Conclusion Experiments on both synthetic and real-world datasets demonstrate the superior performance of the proposed feature selection method combined with supervised learning in three aspects: 1) high classification accuracy, 2) excellent robustness to noise and 3) good stability using to various classification algorithms. PMID:24625071

  6. Microbisporicin gene cluster reveals unusual features of lantibiotic biosynthesis in actinomycetes

    PubMed Central

    Foulston, Lucy C.; Bibb, Mervyn J.

    2010-01-01

    Lantibiotics are ribosomally synthesized, posttranslationally modified peptide antibiotics. The biosynthetic gene cluster for microbisporicin, a potent lantibiotic produced by the actinomycete Microbispora corallina containing chlorinated tryptophan and dihydroxyproline residues, was identified by genome scanning and isolated from an M. corallina cosmid library. Heterologous expression in Nonomuraea sp. ATCC 39727 confirmed that all of the genes required for microbisporicin biosynthesis were present in the cluster. Deletion, in M. corallina, of the gene (mibA) predicted to encode the prepropeptide abolished microbisporicin production. Further deletion analysis revealed insights into the biosynthesis of this unusual and potentially clinically useful lantibiotic, shedding light on mechanisms of regulation and self-resistance. In particular, we report an example of the involvement of a tryptophan halogenase in the modification of a ribosomally synthesized peptide and the pathway-specific regulation of an antibiotic biosynthetic gene cluster by an extracytoplasmic function σ factor–anti-σ factor complex. PMID:20628010

  7. Cranial dystonia, blepharospasm and hemifacial spasm: clinical features and treatment, including the use of botulinum toxin.

    PubMed Central

    Kraft, S P; Lang, A E

    1988-01-01

    Blepharospasm, the most frequent feature of cranial dystonia, and hemifacial spasm are two involuntary movement disorders that affect facial muscles. The cause of blepharospasm and other forms of cranial dystonia is not known. Hemifacial spasm is usually due to compression of the seventh cranial nerve at its exit from the brain stem. Cranial dystonia may result in severe disability. Hemifacial spasm tends to be much less disabling but may cause considerable distress and embarrassment. Patients affected with these disorders are often mistakenly considered to have psychiatric problems. Although the two disorders are quite distinct pathophysiologically, therapy with botulinum toxin has proven very effective in both. We review the clinical features, proposed pathophysiologic features, differential diagnosis and treatment, including the use of botulinum toxin, of cranial dystonia and hemifacial spasm. Images Fig. 2 Fig. 3 PMID:3052771

  8. Prader-Willi Syndrome: A spectrum of anatomical and clinical features.

    PubMed

    Hurren, Bradley J; Flack, Natasha A M S

    2016-07-01

    Prader-Willi Syndrome (PWS) is estimated to affect 400,000 people worldwide. First described clinically in 1956, PWS is now known to be a result of a genetic mutation, involving Chromosome 15. The phenotypical appearance of individuals with the syndrome follows a similar developmental course. During infancy, universal hypotonia accompanied by feeding problems, hypogonadism, and dolichocephaly are evident. Characteristic facial features such as narrow bifrontal diameter, almond-shaped eyes, and small mouth (with downturned corners and thin upper lip) may also be evident at this stage. In early childhood, the craniofacial features become more obvious and a global developmental delay is observed. Simultaneously, individuals develop hyperphagia that leads to excessive or rapid weight gain, which, if untreated, exists throughout their lifespan and may predispose them to numerous, serious health issues. The standard tool for differential diagnosis of PWS is genetic screening; however, clinicians also need to be aware of the characteristic features of this disorder, including differences between the genetic subtypes. As the clinical manifestations of the syndrome vary between individuals and become evident at different developmental time points, early assessment is hindered. This article focuses on the clinical and anatomical manifestations of the syndrome and highlights the areas of discrepancy and limitations within the existing literature. Clin. Anat. 29:590-605, 2016. © 2016 Wiley Periodicals, Inc. PMID:26749552

  9. Solitary rectal ulcer syndrome: Clinical features, pathophysiology, diagnosis and treatment strategies

    PubMed Central

    Zhu, Qing-Chao; Shen, Rong-Rong; Qin, Huan-Long; Wang, Yu

    2014-01-01

    Solitary rectal ulcer syndrome (SRUS) is an uncommon benign disease, characterized by a combination of symptoms, clinical findings and histological abnormalities. Ulcers are only found in 40% of the patients; 20% of the patients have a solitary ulcer, and the rest of the lesions vary in shape and size, from hyperemic mucosa to broad-based polypoid. Men and women are affected equally, with a small predominance in women. SRUS has also been described in children and in the geriatric population. Clinical features include rectal bleeding, copious mucus discharge, prolonged excessive straining, perineal and abdominal pain, feeling of incomplete defecation, constipation, and rarely, rectal prolapse. This disease has well-described histopathological features such as obliteration of the lamina propria by fibrosis and smooth muscle fibers extending from a thickened muscularis mucosa to the lumen. Diffuse collage deposition in the lamina propria and abnormal smooth muscle fiber extensions are sensitive markers for differentiating SRUS from other conditions. However, the etiology remains obscure, and the condition is frequently associated with pelvic floor disorders. SRUS is difficult to treat, and various treatment strategies have been advocated, ranging from conservative management to a variety of surgical procedures. The aim of the present review is to summarize the clinical features, pathophysiology, diagnostic methods and treatment strategies associated with SRUS. PMID:24574747

  10. Childhood trauma associates with clinical features of schizophrenia in a sample of Chinese inpatients.

    PubMed

    Li, Xian-Bin; Li, Qi-Yong; Liu, Jin-Tong; Zhang, Liang; Tang, Yi-Lang; Wang, Chuan-Yue

    2015-08-30

    This study examined the association between childhood trauma and clinical features, comorbid anxiety and post-traumatic stress disorder (PTSD) symptoms, and suicidal and aggressive behaviors in Chinese patients with schizophrenia. The Childhood Trauma Questionnaire - Short Form (CTQ-SF), the Impact of Events Scale - Revised (IES-R), and the State-Trait Anxiety Inventory (STAI) were administered to 182 Chinese inpatients with schizophrenia. The relationship between the severity and the number of traumic experiences and clinical features were analyzed. Physical neglect (PN) in childhood was reported in 71.7% of this sample, followed by emotional neglect (EN, 58.6%), sexual abuse (SA, 39.9%), emotional abuse (EA, 31.7%) and physical abuse (PA, 22.2%). Significant negative correlations existed between age of onset and the EA scores. Significant positive correlations were found between the subscores of IES-R, STAI and CTQ-SF. Patients with history of suicidal or aggressive behaviors had significantly higher trauma scores than patients without such behaviors. Exposure to childhood trauma is associated with early age of onset, more PTSD and anxiety symptoms, and history of suicidal and aggressive behaviors. A dose-effect may exist between severity, number of trauma experiences, and clinical features. PMID:26096662

  11. Clinical Features of 705 Borrelia burgdorferi Seropositive Patients in an Endemic Area of Northern Italy

    PubMed Central

    Ruscio, Maurizio; Trotter, Davide

    2014-01-01

    Background. Lyme Borreliosis is a multisystemic infection caused by spirochetes of Borrelia burgdorferi sensu lato complex. The features of Lyme Borreliosis may differ in the various geographical areas, primarily between the manifestations found in America and those found in Europe and Asia. Objective. to describe the clinical features of Lyme Borreliosis in an endemic geographic area such as Friuli-Venezia Giulia in the Northeastern part of Italy. Methods. The medical records of patients resulted seropositive for Borrelia burgdorferi have been retrospectively recorded and analyzed. Results. Seven hundred and five patients met the inclusion criteria, 363 males and 342 females. Erythema migrans was the most common manifestation, detected in 437 patients. Other classical cutaneous manifestations included 58 cases of multiple erythema migrans, 7 lymphadenosis benigna cutis, and 18 acrodermatitis chronica atrophicans. The musculoskeletal system was involved in 511 patients. Four hundred and sixty patients presented a neurological involvement. Flu-like symptoms preceded or accompanied or were the only clinical feature in 119 patients. Comments. The manifestations of Lyme borreliosis recorded in this study are similar to the ones of other endemic areas in Europe, even if there are some peculiar features which are different from those reported in Northern Europe and in the USA. PMID:24550705

  12. Identifying ultrasound and clinical features of breast cancer molecular subtypes by ensemble decision.

    PubMed

    Zhang, Lei; Li, Jing; Xiao, Yun; Cui, Hao; Du, Guoqing; Wang, Ying; Li, Ziyao; Wu, Tong; Li, Xia; Tian, Jiawei

    2015-01-01

    Breast cancer is molecularly heterogeneous and categorized into four molecular subtypes: Luminal-A, Luminal-B, HER2-amplified and Triple-negative. In this study, we aimed to apply an ensemble decision approach to identify the ultrasound and clinical features related to the molecular subtypes. We collected ultrasound and clinical features from 1,000 breast cancer patients and performed immunohistochemistry on these samples. We used the ensemble decision approach to select unique features and to construct decision models. The decision model for Luminal-A subtype was constructed based on the presence of an echogenic halo and post-acoustic shadowing or indifference. The decision model for Luminal-B subtype was constructed based on the absence of an echogenic halo and vascularity. The decision model for HER2-amplified subtype was constructed based on the presence of post-acoustic enhancement, calcification, vascularity and advanced age. The model for Triple-negative subtype followed two rules. One was based on irregular shape, lobulate margin contour, the absence of calcification and hypovascularity, whereas the other was based on oval shape, hypovascularity and micro-lobulate margin contour. The accuracies of the models were 83.8%, 77.4%, 87.9% and 92.7%, respectively. We identified specific features of each molecular subtype and expanded the scope of ultrasound for making diagnoses using these decision models. PMID:26046791

  13. Frequency of Distinguishing Clinical Features in Vogt-Koyanagi-Harada disease

    PubMed Central

    Rao, Narsing A.; Gupta, Amod; Dustin, Laurie; Chee, Soon Phaik; Okada, Annabelle A.; Khairallah, Moncef; Bodaghi, Bahram; Lehoang, Phuc; Accorinti, Massimo; Mochizuki, Manabu; Prabriputaloong, Tisha; Read, Russell W.

    2009-01-01

    Purpose To determine the frequency of occurrence of limited clinical features which distinguish patients with Vogt-Koyanagi-Harada (VKH) disease from those with non-VKH uveitis. Design Comparative case series. Participants 1147 total patients. Methods All patients with bilateral ocular inflammatory disease presenting to any of ten uveitis centers in the three month period between 2006-January-01 and 2006-March-31 (inclusive) were asked to participate. The clinical and historical features of disease were obtained from the participants via direct interview and chart review. Patients were stratified based on whether they were diagnosed with VKH disease or non-VKH uveitis for statistical analysis. Main Outcome Measures Presence or absence of various clinical features in the two populations. Results Of 1147 patients, 180 were diagnosed with VKH disease and 967 with non-VKH uveitis. Hispanics and Asians were more likely to be diagnosed with VKH than non-VKH disease compared to other ethnicities. In acute disease, the finding of exudative retinal detachment was most likely to be found in VKH disease with a positive predictive value (PPV) of 100 and negative predictive value (NPV) of 88.4, while in chronic disease, sunset glow fundus was most likely to be found, with a PPV of 94.5 and NPV of 89.2. Conclusions Numerous clinical findings have been described in the past as important in the diagnosis of VKH. The current study reveals that of these, two are highly specific to this entity in an ethnically and geographically diverse group of patients with non-traumatic bilateral uveitis. These clinical findings are 1. exudative retinal detachment during acute disease and 2. sunset glow fundus during the chronic phase of the disease. PMID:20036008

  14. Sex Differences in Clinical Features of Early, Treated Parkinson’s Disease

    PubMed Central

    Augustine, Erika F.; Pérez, Adriana; Dhall, Rohit; Umeh, Chizoba C.; Videnovic, Aleksandar; Cambi, Franca; Wills, Anne-Marie A.; Elm, Jordan J.; Zweig, Richard M.; Shulman, Lisa M.; Nance, Martha A.; Bainbridge, Jacquelyn; Suchowersky, Oksana

    2015-01-01

    Introduction To improve our understanding of sex differences in the clinical characteristics of Parkinson’s Disease, we sought to examine differences in the clinical features and disease severity of men and women with early treated Parkinson’s Disease (PD) enrolled in a large-scale clinical trial. Methods Analysis was performed of baseline data from the National Institutes of Health Exploratory Trials in Parkinson’s Disease (NET-PD) Long-term Study-1, a randomized, multi-center, double-blind, placebo-controlled study of 10 grams of oral creatine/day in individuals with early, treated PD. We compared mean age at symptom onset, age at PD diagnosis, and age at randomization between men and women using t-test statistics. Sex differences in clinical features were evaluated, including: symptoms at diagnosis (motor) and symptoms at randomization (motor, non-motor, and daily functioning). Results 1,741 participants were enrolled (62.5% male). No differences were detected in mean age at PD onset, age at PD diagnosis, age at randomization, motor symptoms, or daily functioning between men and women. Differences in non-motor symptoms were observed, with women demonstrating better performance compared to men on SCOPA-COG (Z = 5.064, p<0.0001) and Symbol Digit Modality measures (Z = 5.221, p<0.0001). Conclusions Overall, men and women did not demonstrate differences in clinical motor features early in the course of PD. However, the differences observed in non-motor cognitive symptoms suggests further assessment of the influence of sex on non-motor symptoms in later stages of PD is warranted. PMID:26171861

  15. SOCS3 Genetic Polymorphism Is Associated With Clinical Features and Prognosis of Hepatocellular Carcinoma Patients Receiving Hepatectomy

    PubMed Central

    Jiang, Bei-ge; Yang, Yuan; Liu, Hui; Gu, Fang-ming; Yang, Yun; Zhao, Lin-Hao; Yuan, Sheng-xian; Wang, Ruo-yu; Zhang, Jin; Zhou, Wei-ping

    2015-01-01

    Abstract Previous studies showed that suppressor of cytokine signaling 3 (SOCS3) protein is associated with incidence and progression of hepatocellular carcinoma (HCC); however, the association between the genetic polymorphism of SOCS3 gene and HCC remains unknown. A total of 254 HCC patients and 354 healthy controls were enrolled. All HCC patients underwent partial hepatectomy as initial treatment and were followed. Three SOCS3 gene polymorphisms, namely, rs4969170 A>G, rs8064821 C>T, and rs12953258 C>A were determined. Our data show that the rs4969170 A>G polymorphism dramatically affects the susceptibility to HCC in our cohorts. Logistic regression analyses revealed that the rs4969170 GG is a risk factor for HCC after the adjustment with confounding factors. The rs4969170A>G polymorphism is also associated with the clinical features of HCC patients and predicts the postoperative relapse-free survival and overall survival. The rs4969170GG genotype carrier had a worse prognosis than the rs4969170AG and rs4969170AA carrier. Our findings suggest that the rs4969170A>G polymorphism of SOCS3 gene may be used as a prognostic predictor for HCC patients who underwent surgical treatment. PMID:26447993

  16. The human ubiquitin-52 amino acid fusion protein gene shares several structural features with mammalian ribosomal protein genes.

    PubMed Central

    Baker, R T; Board, P G

    1991-01-01

    Complementary DNA clones encoding ubiquitin fused to a 52 amino acid tail protein were isolated from human placental and adrenal gland cDNA libraries. The deduced human 52 amino acid tail protein is very similar to the homologous protein from other species, including the conservation of the putative metal-binding, nucleic acid-binding domain observed in these proteins. Northern blot analysis with a tail-specific probe indicated that the previously identified UbA mRNA species most likely represents comigrating transcripts of the 52 amino acid tail (UbA52) and 80 amino acid tail (UbA80) ubiquitin fusion genes. The UbA52 gene was isolated from a human genomic library and consists of five exons distributed over 3400 base pairs. One intron is in the 5' non-coding region, two interrupt the single ubiquitin coding unit, and the fourth intron is within the tail coding region. Several members of the Alu family of repetitive DNA are associated with the gene. The UbA52 promoter has several features in common with mammalian ribosomal protein genes, including its location in a CpG-rich island, initiation of transcription within a polypyrimidine tract, the lack of a consensus TATA motif, and the presence of Sp1 binding sites, observations that are consistent with the recent identification of the ubiquitin-free tail proteins as ribosomal proteins. Thus, in spite of its unusual feature of being translationally fused to ubiquitin, the 52 amino acid tail ribosomal protein is expressed from a structurally typical ribosomal protein gene. Images PMID:1850507

  17. Evaluation of the association between perineural invasion and clinical and histopathological features of cervical cancer

    PubMed Central

    Wei, You-Sheng; Yao, De-Sheng; Long, Ying

    2016-01-01

    Perineural invasion (PNI) has been investigated as a new prognostic factor in a number of carcinomas. However, studies on PNI in cervical cancer are limited, and inconsistent conclusions have been reported by different groups. The aim of the present study was to analyze the relationship between perineural invasion (PNI) and clinical and histopathological features of cervical cancer, and to evaluate the clinical significance of PNI of cervical cancer. Retrospective review identified 206 patients with cervical cancer who underwent radical hysterectomy plus pelvic lymphadenectomy between December 2012 and August 2014. The association between PNI and clinical and histopathological features of cervical cancer and post-operative radiotherapy was evaluated based on univariate and multivariate analyses. PNI of cervical cancer was identified in 33 of 206 (16%) cervical cancer patients. Univariate analysis demonstrated that PNI was associated with clinical stage, tumor grade, tumor size, depth of invasion, lymphovascular space invasion (LVSI), and lymph node metastasis (P<0.05), but not associated with age and histopathological types (P>0.05). Multivariate analysis suggests that LVSI and lymph node metastasis were associated with PNI of cervical cancer (P<0.05). In addition, post-operative radiotherapy was significantly more recommended for patients with PNI than those without PNI (P<0.001). In conclusion, PNI of cervical cancer is associated with LVSI and lymph node metastasis and can be used as an index for the determination of post-operative radiotherapy for cervical cancer patients. PMID:27588197

  18. Evaluation of the Clinical and Sociodemographic Features of Turkish Patients with Vitiligo.

    PubMed

    Oguz Topal, Ilteris; Duman, Hatice; Gungor, Sule; Kocaturk, Emek; Kuteyla Can, Pelin

    2016-06-01

    Vitiligo is an acquired, pigmentary skin disorder that affects about 0.1-4.0% of the population. In this study, we aimed to investigate the disease features such as age of onset, disease duration, clinical and sociodemographic characteristics, and laboratory parameters of patients with vitiligo. A hundred patients who were in follow-up for vitiligo between the period of June 2013 and May 2014 were included in the study. The clinical features and laboratory parameters were retrospectively obtained from the records of the patients. The mean age was 34.9±16.8 years. The most common clinical types were focal and acrofacial. Facial involvement was the most common localization. Forty-five (45%) patients had an associated systemic disease. Autoimmune thyroid disease, essential hypertension, and alopecia areata, which were observed in 28%, 8%, and 5% of patients, respectively, were the most common associated diseases. Twenty-one percent of the patients had low ferritin levels, 20% had low iron levels, 12% had low vitamin B12 levels, and 1% had low folic acid levels. The prevalence of anti-TG (anti-thyroglobulin) and anti-TPO (anti-thyroid peroxidase) antibodies were found 17% and 27% of the patients, respectively. We found that the clinical characteristics of vitiligo in our patients were similar to those in other studies. We observed laboratory abnormalities and accompanying diseases associated with vitiligo. Therefore we conclude that laboratory examinations including thyroid antibodies and regular follow-up of these patients are essential. PMID:27477172

  19. Clinical and mutational features of X-linked agammaglobulinemia in Mexico.

    PubMed

    García-García, E; Staines-Boone, A T; Vargas-Hernández, A; González-Serrano, M E; Carrillo-Tapia, E; Mogica-Martínez, D; Berrón-Ruíz, L; Segura-Mendez, N H; Espinosa-Rosales, F J; Yamazaki-Nakashimada, M A; Santos-Argumedo, L; López-Herrera, G

    2016-04-01

    X-linked agammaglobulinemia (XLA) is caused by BTK mutations, patients typically show <2% of peripheral B cells and reduced levels of all immunoglobulins; they suffer from recurrent infections of bacterial origin; however, viral infections, autoimmune-like diseases, and an increased risk of developing gastric cancer are also reported. In this work, we report the BTK mutations and clinical features of 12 patients diagnosed with XLA. Furthermore, a clinical revision is also presented for an additional cohort of previously reported patients with XLA. Four novel mutations were identified, one of these located in the previously reported mutation refractory SH3 domain. Clinical data support previous reports accounting for frequent respiratory, gastrointestinal tract infections and other symptoms such as the occurrence of reactive arthritis in 19.2% of the patients. An equal proportion of patients developed septic arthritis; missense mutations and mutations in SH1, SH2 and PH domains predominated in patients who developed arthritis. PMID:26960951

  20. Interstitial Mycosis Fungoides With Lichen Sclerosus-Like Clinical and Histopathological Features.

    PubMed

    Tekin, Burak; Kempf, Werner; Seckin, Dilek; Ergun, Tulin; Yucelten, Deniz; Demirkesen, Cuyan

    2016-02-01

    Mycosis fungoides (MF) simulates a variety of dermatologic disorders histopathologically and clinically, well deserving the designation of a great mimicker. Interstitial MF is a rare, but well-recognized histopathological variant resembling the interstitial form of granuloma annulare or the inflammatory phase of morphea. From a clinical standpoint, MF can have a wide array of manifestations, including an anecdotal presentation with lesions clinically suggestive of lichen sclerosus (LS). We herein report a 25-year-old man with a history of patch-stage MF who later developed widespread LS-like lesions histopathologically consistent with interstitial MF. In some biopsies, additional features resembling LS were discerned. We think that our case might represent a unique variant of interstitial MF presenting with LS-like lesions. The diagnostic challenge arising from this uncommon presentation is discussed together with review of the literature. PMID:26630682

  1. Nitrogen cycling in Yellowstone National Park thermal features: using gene expression to reveal ecological function

    NASA Astrophysics Data System (ADS)

    Lafree, S. T.; Burton, M. S.; Meyer-Dombard, D. R.

    2010-12-01

    Studies of biodiversity, metabolic strategies, and functional ecology in modern hydrothermal systems have the potential to provide insight into the metabolism and evolution of life. The geochemical and microbial diversity present at Yellowstone National Park (YNP), Wyoming, USA, makes it an ideal place for studying the functional ecology and metabolic processes of prokaryotic organisms. While much work in terrestrial hydrothermal features is focused on phylogenetic and geochemical analyses, a few recent investigations in YNP and other hydrothermal areas have focused on “gene hunting”: screening thermal sediment and biofilm samples for the presence of genes utilized in specific metabolic processes [2, 3, 6, 7, 8]. Although research has evaluated and confirmed the presence of many of these genes in various thermophilic microbial communities, the existence of a gene in the DNA of an organism does not verify its use, and few researchers have done work to confirm the utilization (expression) of the genes discovered in thermal samples [1, 6, 7, 8]. Disequilibrium between reduced hydrothermal fluid of YNP thermal features and the atmosphere provides a copious source of potential energy to be harnessed through microbial metabolic processes, with NO3- and NO2- serving as the preferred electron acceptors and top energy sources after O2 [4, 5]. Consequentially, nitrogen cycling likely plays a vital role in microbial metabolic processes, as well as nutrient availability. This study explores the presence and utilization of functional genes that are key in steps of the nitrogen cycle, such as nitrogen fixation (NifH), denitrification (nirKS), and ammonia oxidation (amoA). Both DNA and RNA were extracted from thermal sediment and streamer biofilm communities collected in the chemosynthetic zone of various thermal features of the Sentinel Meadows Group in Lower Geyser Basin, YNP. Extracted DNA and reverse transcribed RNA (cDNA) were amplified using the polymerase chain

  2. Drosophila Gene Expression Pattern Annotation Using Sparse Features and Term-Term Interactions

    PubMed Central

    Ji, Shuiwang; Yuan, Lei; Li, Ying-Xin; Zhou, Zhi-Hua; Kumar, Sudhir; Ye, Jieping

    2010-01-01

    The Drosophila gene expression pattern images document the spatial and temporal dynamics of gene expression and they are valuable tools for explicating the gene functions, interaction, and networks during Drosophila embryogenesis. To provide text-based pattern searching, the images in the Berkeley Drosophila Genome Project (BDGP) study are annotated with ontology terms manually by human curators. We present a systematic approach for automating this task, because the number of images needing text descriptions is now rapidly increasing. We consider both improved feature representation and novel learning formulation to boost the annotation performance. For feature representation, we adapt the bag-of-words scheme commonly used in visual recognition problems so that the image group information in the BDGP study is retained. Moreover, images from multiple views can be integrated naturally in this representation. To reduce the quantization error caused by the bag-of-words representation, we propose an improved feature representation scheme based on the sparse learning technique. In the design of learning formulation, we propose a local regularization framework that can incorporate the correlations among terms explicitly. We further show that the resulting optimization problem admits an analytical solution. Experimental results show that the representation based on sparse learning outperforms the bag-of-words representation significantly. Results also show that incorporation of the term-term correlations improves the annotation performance consistently. PMID:21614142

  3. Clinical features of dementia with lewy bodies in 35 Chinese patients

    PubMed Central

    2014-01-01

    Objective To investigate the clinical features of dementia with Lewy bodies (DLB) in a Chinese population. Methods Computer-based online searches through China Biology Medicine disc and China National Knowledge Infrastructure were performed to collect case reports of DLB published between 1980 and 2012. Clinical characteristics were analyzed. Results A total of 18 studies comprising 35 patients (26 males and 9 females) were included. The mean age at onset was 67.2 ± 9.8 years. Onset was characterized by memory impairment and accounted for 58.8% of all cases, followed by parkinsonism (11.8%), visual hallucinations (8.8%), and compulsive personality disorder (2.9%). The other patients (17.6%) presented two of the three core features of DLB at onset. With disease progression, parkinsonism was reported in 100% of cases, followed by visual hallucinations (97.1%), psychiatric symptoms (85.7%), severe neuroleptic sensitivity (81.8%), fluctuating cognition (68.6%), repeated falls (40.0%), sleep disorders (22.9%), and transient loss of consciousness (17.1%). 26 patients who were subjected to Mini-Mental State Examination scored ≤ 24. 10 patients presented relative preservation of hippocampus and medial temporal lobe structures on CT/MRI scan. Occipital hypometabolism occurred in 2 of 3 patients who underwent SPECT/PET perfusion scan. 12 patients showed an increasing of slow frequency activity on EEG, prominently in frontal and temporal lobes. Conclusions DLB often strikes elderly individuals. Its clinical core features are dementia, fluctuating cognition, recurrent visual hallucinations and spontaneous features of parkinsonism. Neuropsychological, neuroimaging and EEG examinations may improve the diagnostic accuracy and discriminate DLB from other dementias. PMID:24398160

  4. Clinicopathologic Features and Clinical Outcomes of Esophageal Gastrointestinal Stromal Tumor: Evaluation of a Pooled Case Series.

    PubMed

    Feng, Fan; Tian, Yangzi; Liu, Zhen; Xu, Guanghui; Liu, Shushang; Guo, Man; Lian, Xiao; Fan, Daiming; Zhang, Hongwei

    2016-01-01

    Clinicopathologic features and clinical outcomes of gastrointestinal stromal tumors (GISTs) in esophagus are limited, because of the relatively rare incidence of esophageal GISTs. Therefore, the aim of the current study was to investigate the clinicopathologic features and clinical outcomes of esophageal GISTs, and to investigate the potential factors that may predict prognosis.Esophageal GIST cases were obtained from our center and from case reports and clinical studies extracted from MEDLINE. Clinicopathologic features and survivals were analyzed and compared with gastric GISTs from our center.The most common location was lower esophagus (86.84%), followed by middle and upper esophagus (11.40% and 1.76%). The majority of esophageal GISTs were classified as high-risk category (70.83%). Mitotic index was correlated with histologic type, mutational status, and tumor size. The 5-year disease-free survival and disease-specific survival were 65.1% and 65.9%, respectively. Tumor size, mitotic index, and National Institutes of Health risk classification were associated with prognosis of esophageal GISTs. Only tumor size, however, was the independent risk factor for the prognosis of esophageal GISTs. In comparison to gastric GISTs, the distribution of tumor size, histologic type, and National Institutes of Health risk classification were significantly different between esophageal GISTs and gastric GISTs. The disease-free survival and disease-specific survival of esophageal GISTs were significantly lower than that of gastric GISTs.The most common location for esophageal GISTs was lower esophagus, and most of the esophageal GISTs are high-risk category. Tumor size was the independent risk factor for the prognosis of esophageal GISTs. Esophageal GISTs differ significantly from gastric GISTs in respect to clinicopathologic features. The prognosis of esophageal GISTs was worse than that of gastric GISTs. PMID:26765432

  5. Clinical and epidemiological features of coryneform skin infections at a tertiary hospital

    PubMed Central

    Pinto, Malcolm; Hundi, Ganesh Kamath; Bhat, Ramesh Marne; Bala, Nanda Kishore; Dandekeri, Sukumar; Martis, Jacintha; Kambil, Srinath M.

    2016-01-01

    Background: Skin infections caused by coryneform bacteria are common dermatological conditions. However, to the best of our knowledge, no studies are available on the clinical characteristics and epidemiological features of this group of disorders as one entity from India and abroad. Aims: To study the clinical and epidemiological features of coryneform skin infections Methods: A total of 75 patients presenting with clinically distinctive lesions of pitted keratolysis, erythrasma and trichobacteriosis to our hospital were included in the study. Cases were interviewed with particular emphasis on epidemiological features and the various clinical findings were recorded. Investigations like Gram's stain, Wood's light examination, 10% KOH scrapings, were done in selected cases to ascertain the diagnosis. Results: Pitted keratolysis was more common in the age group of 31-40 years (40%) with a male preponderance (76.7%), most commonly affecting pressure bearing areas of the soles with malodour (86.7%) and frequent contact with water (58.3%) constituting the most important presenting symptom and provocating factor respectively. Erythrasma affected both male and female patients equally and was more commonly detected in patients with a BMI > 23kg/m2 (62.5%) and in diabetics (50%). All patients with trichobacteriosis presented with yellow coloured concretions in the axillae. Bromhidrosis (71.4%) and failure to regularly use an axillary deodorant (71.4%) were the most common presenting symptom and predisposing factor respectively. Conclusion: Coryneform skin infections are common dermatological conditions, though epidemiological data are fragmentary. Hyperhidrosis is a common predisposing factor to all three coryneform skin infections. Asymmetrical distribution of pits has been reported in our study. Diabetic status needs to be evaluated in all patients with erythrasma. Woods lamp examination forms an indispensible tool to diagnose erythrasma and trichobacteriosis. PMID

  6. A Novel Fibrillin 1 Gene Mutation Leading to Marfan Syndrome with Minimal Cardiac Features

    PubMed Central

    Martínez-Quintana, E; Rodríguez-González, F; Garay-Sánchez, P; Tugores, A

    2014-01-01

    Marfan syndrome is an autosomal dominant disorder of the connective tissue, characterized by early development of thoracic aortic aneurysms and/or dissections, accompanied by ocular and/or skeletal involvement, and is caused by mutations in the fibrillin 1 (FBN1) gene. We report on a patient with ectopia lentis and a nonprogressive aortic root dilatation who presented with a novel mutation affecting a conserved cysteine residue present in a calcium-binding epidermal growth factor-like domain of FBN1 (ENSP00000325527, p.Cys538Phe; Chr15:48,805,751 G>T), as revealed by complete sequencing of the FBN1 gene exons and flanking sequences. Identification of the mutation led to genetic screening of apparently asymptomatic family members, allowing the detection of characteristic ocular phenotypes in the absence of typical cardiac Marfan features. This finding stresses the importance of genetic screening of asymptomatic relatives for FBN1 gene mutation carriers. PMID:25337071

  7. Feasibility of feature-based indexing, clustering, and search of clinical trials: A case study of breast cancer trials from ClinicalTrials.gov

    PubMed Central

    Boland, Mary Regina; Miotto, Riccardo; Gao, Junfeng; Weng, Chunhua

    2013-01-01

    Summary Background When standard therapies fail, clinical trials provide experimental treatment opportunities for patients with drug-resistant illnesses or terminal diseases. Clinical Trials can also provide free treatment and education for individuals who otherwise may not have access to such care. To find relevant clinical trials, patients often search online; however, they often encounter a significant barrier due to the large number of trials and in-effective indexing methods for reducing the trial search space. Objectives This study explores the feasibility of feature-based indexing, clustering, and search of clinical trials and informs designs to automate these processes. Methods We decomposed 80 randomly selected stage III breast cancer clinical trials into a vector of eligibility features, which were organized into a hierarchy. We clustered trials based on their eligibility feature similarities. In a simulated search process, manually selected features were used to generate specific eligibility questions to filter trials iteratively. Results We extracted 1,437 distinct eligibility features and achieved an inter-rater agreement of 0.73 for feature extraction for 37 frequent features occurring in more than 20 trials. Using all the 1,437 features we stratified the 80 trials into six clusters containing trials recruiting similar patients by patient-characteristic features, five clusters by disease-characteristic features, and two clusters by mixed features. Most of the features were mapped to one or more Unified Medical Language System (UMLS) concepts, demonstrating the utility of named entity recognition prior to mapping with the UMLS for automatic feature extraction. Conclusions It is feasible to develop feature-based indexing and clustering methods for clinical trials to identify trials with similar target populations and to improve trial search efficiency. PMID:23666475

  8. Perineural Infiltration of Cutaneous Squamous Cell Carcinoma and Basal Cell Carcinoma Without Clinical Features

    SciTech Connect

    Lin, Charles; Tripcony, Lee; Keller, Jacqui; Poulsen, Michael; Martin, Jarad; Jackson, James; Dickie, Graeme

    2012-01-01

    Purpose: To review the factors that influence outcome and patterns of relapse in patients with cutaneous squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) with perineural infiltration (PNI) without clinical or radiologic features, treated with surgery and radiotherapy. Methods and Materials: Between 1991 and 2004, 222 patients with SCC or BCC with PNI on pathologic examination but without clinical or radiologic PNI features were identified. Charts were reviewed retrospectively and relevant data collected. All patients were treated with curative intent; all had radiotherapy, and most had surgery. The primary endpoint was 5-year relapse-free survival from the time of diagnosis. Results: Patients with SCC did significantly worse than those with BCC (5-year relapse-free survival, 78% vs. 91%; p < 0.01). Squamous cell carcinoma with PNI at recurrence did significantly worse than de novo in terms of 5-year local failure (40% vs. 19%; p < 0.01) and regional relapse (29% vs. 5%; p < 0.01). Depth of invasion was also a significant factor. Of the PNI-specific factors for SCC, focal PNI did significantly better than more-extensive PNI, but involved nerve diameter or presence of PNI at the periphery of the tumor were not significant factors. Conclusions: Radiotherapy in conjunction with surgery offers an acceptable outcome for cutaneous SCC and BCC with PNI. This study suggests that focal PNI is not an adverse feature.

  9. Prioritizing Clinically Relevant Copy Number Variation from Genetic Interactions and Gene Function Data

    PubMed Central

    Foong, Justin; Girdea, Marta; Stavropoulos, James; Brudno, Michael

    2015-01-01

    It is becoming increasingly necessary to develop computerized methods for identifying the few disease-causing variants from hundreds discovered in each individual patient. This problem is especially relevant for Copy Number Variants (CNVs), which can be cheaply interrogated via low-cost hybridization arrays commonly used in clinical practice. We present a method to predict the disease relevance of CNVs that combines functional context and clinical phenotype to discover clinically harmful CNVs (and likely causative genes) in patients with a variety of phenotypes. We compare several feature and gene weighing systems for classifying both genes and CNVs. We combined the best performing methodologies and parameters on over 2,500 Agilent CGH 180k Microarray CNVs derived from 140 patients. Our method achieved an F-score of 91.59%, with 87.08% precision and 97.00% recall. Our methods are freely available at https://github.com/compbio-UofT/cnv-prioritization. Our dataset is included with the supplementary information. PMID:26437450

  10. Oropharyngeal Dysphagia in Dermatomyositis: Associations with Clinical and Laboratory Features Including Autoantibodies

    PubMed Central

    Mugii, Naoki; Hasegawa, Minoru; Matsushita, Takashi; Hamaguchi, Yasuhito; Oohata, Sacihe; Okita, Hirokazu; Yahata, Tetsutarou; Someya, Fujiko; Inoue, Katsumi; Murono, Shigeyuki; Fujimoto, Manabu; Takehara, Kazuhiko

    2016-01-01

    Objective Dysphagia develops with low frequency in patients with dermatomyositis. Our objective was to determine the clinical and laboratory features that can estimate the development of dysphagia in dermatomyositis. Methods This study included 92 Japanese patients with adult-onset dermatomyositis. The associations between dysphagia and clinical and laboratory features including disease-specific autoantibodies determined by immunoprecipitation assays were analyzed. Results Videofluoroscopy swallow study (VFSS) was performed for all patients with clinical dysphagia (n = 13, 14.1%) but not for patients without clinical dysphagia. Typical findings of dysphagia (pharyngeal pooling, n = 11 and/or nasal regurgitation, n = 4) was detected by VFSS in all patients with clinical dysphagia. Eleven patients with dysphagia (84.6%) had anti-transcription intermediary factor 1γ (TIF-1γ) antibody. By univariate analysis, the average age and the male to female ratio, internal malignancy, and anti-TIF-1γ antibody were significantly higher and the frequency of interstitial lung diseases and manual muscle testing (MMT) scores of sternomastoid and dertoid muscles were significantly lower in patients with dysphagia than in patients without dysphagia. Among patients with anti-TIF-1γ antibody, the mean age, the ratios of male to female and internal malignancy were significantly higher and mean MMT scores of sternomastoid muscle were significantly lower in patients with dysphagia compared with patients without dysphagia. By multivariable analysis, the risk of dysphagia was strongly associated with the existence of internal malignancy and ant-TIF-1γ antibody and was also associated with reduced scores of manual muscle test of sternomastoid muscle. Dysphagia was markedly improved after the treatment against myositis in all 13 patients. Conclusion These findings indicate that dysphagia can develop frequently in patients with internal malignancy, anti-TIF-1γ antibody, or severe muscle

  11. Clinical and pathological features of familial frontotemporal dementia caused by C9ORF72 mutation on chromosome 9p

    PubMed Central

    Hsiung, Ging-Yuek R.; DeJesus-Hernandez, Mariely; Feldman, Howard H.; Sengdy, Pheth; Bouchard-Kerr, Phoenix; Dwosh, Emily; Butler, Rachel; Leung, Bonnie; Fok, Alice; Rutherford, Nicola J.; Baker, Matt; Rademakers, Rosa

    2012-01-01

    Frontotemporal dementia and amyotrophic lateral sclerosis are closely related clinical syndromes with overlapping molecular pathogenesis. Several families have been reported with members affected by frontotemporal dementia, amyotrophic lateral sclerosis or both, which show genetic linkage to a region on chromosome 9p21. Recently, two studies identified the FTD/ALS gene defect on chromosome 9p as an expanded GGGGCC hexanucleotide repeat in a non-coding region of the chromosome 9 open reading frame 72 gene (C9ORF72). In the present study, we provide detailed analysis of the clinical features and neuropathology for 16 unrelated families with frontotemporal dementia caused by the C9ORF72 mutation. All had an autosomal dominant pattern of inheritance. Eight families had a combination of frontotemporal dementia and amyotrophic lateral sclerosis while the other eight had a pure frontotemporal dementia phenotype. Clinical information was available for 30 affected members of the 16 families. There was wide variation in age of onset (mean = 54.3, range = 34–74 years) and disease duration (mean = 5.3, range = 1–16 years). Early diagnoses included behavioural variant frontotemporal dementia (n = 15), progressive non-fluent aphasia (n = 5), amyotrophic lateral sclerosis (n = 9) and progressive non-fluent aphasia–amyotrophic lateral sclerosis (n = 1). Heterogeneity in clinical presentation was also common within families. However, there was a tendency for the phenotypes to converge with disease progression; seven subjects had final clinical diagnoses of both frontotemporal dementia and amyotrophic lateral sclerosis and all of those with an initial progressive non-fluent aphasia diagnosis subsequently developed significant behavioural abnormalities. Twenty-one affected family members came to autopsy and all were found to have transactive response DNA binding protein with Mr 43 kD (TDP-43) pathology in a wide neuroanatomical distribution. All

  12. Clinical and pathological features of familial frontotemporal dementia caused by C9ORF72 mutation on chromosome 9p.

    PubMed

    Hsiung, Ging-Yuek R; DeJesus-Hernandez, Mariely; Feldman, Howard H; Sengdy, Pheth; Bouchard-Kerr, Phoenix; Dwosh, Emily; Butler, Rachel; Leung, Bonnie; Fok, Alice; Rutherford, Nicola J; Baker, Matt; Rademakers, Rosa; Mackenzie, Ian R A

    2012-03-01

    Frontotemporal dementia and amyotrophic lateral sclerosis are closely related clinical syndromes with overlapping molecular pathogenesis. Several families have been reported with members affected by frontotemporal dementia, amyotrophic lateral sclerosis or both, which show genetic linkage to a region on chromosome 9p21. Recently, two studies identified the FTD/ALS gene defect on chromosome 9p as an expanded GGGGCC hexanucleotide repeat in a non-coding region of the chromosome 9 open reading frame 72 gene (C9ORF72). In the present study, we provide detailed analysis of the clinical features and neuropathology for 16 unrelated families with frontotemporal dementia caused by the C9ORF72 mutation. All had an autosomal dominant pattern of inheritance. Eight families had a combination of frontotemporal dementia and amyotrophic lateral sclerosis while the other eight had a pure frontotemporal dementia phenotype. Clinical information was available for 30 affected members of the 16 families. There was wide variation in age of onset (mean = 54.3, range = 34-74 years) and disease duration (mean = 5.3, range = 1-16 years). Early diagnoses included behavioural variant frontotemporal dementia (n = 15), progressive non-fluent aphasia (n = 5), amyotrophic lateral sclerosis (n = 9) and progressive non-fluent aphasia-amyotrophic lateral sclerosis (n = 1). Heterogeneity in clinical presentation was also common within families. However, there was a tendency for the phenotypes to converge with disease progression; seven subjects had final clinical diagnoses of both frontotemporal dementia and amyotrophic lateral sclerosis and all of those with an initial progressive non-fluent aphasia diagnosis subsequently developed significant behavioural abnormalities. Twenty-one affected family members came to autopsy and all were found to have transactive response DNA binding protein with M(r) 43 kD (TDP-43) pathology in a wide neuroanatomical distribution. All had involvement of the extramotor

  13. Clinical features and prognosis of herpetic anterior uveitis: a retrospective study of 111 cases.

    PubMed

    Tugal-Tutkun, Ilknur; Otük-Yasar, Berna; Altinkurt, Emre

    2010-10-01

    To describe the clinical features and outcomes in patients with herpetic anterior uveitis. We reviewed the records of 111 patients with a clinical diagnosis of herpetic anterior uveitis seen at the Department of Ophthalmology, Istanbul Faculty of Medicine, from January 1996 to December 2006. Demographic and clinical features, recurrence rate, and visual outcome were analyzed. Fifty patients were male, 61 were female. Mean age at presentation was 39.2 ± 16.5 (6-74) years. Three atopic patients had bilateral involvement. Twelve patients had active or a past episode of herpes zoster ophthalmicus. Ocular findings were granulamatous anterior uveitis (93%), active keratitis or corneal scars (57%), elevated intraocular pressure (51%), iris atrophy (48%), distorted pupil (25%), and posterior synechiae (26%). Secondary glaucoma developed in two patients. None of the patients had posterior segment complications. The recurrence rate was 0.45/person-year. Topical corticosteroids and oral antiviral therapy were administered to all patients during active episodes. Long-term prophylactic oral acyclovir was used in 13%. Final visual acuity was worse than 0.5 in 17% of the involved eyes and was due to corneal scarring or cataract formation. Patients with iridocyclitis only had no permanent visual loss. Herpetic anterior uveitis is a recurrent granulomatous disease commonly associated with corneal involvement, iris atrophy, and transient intraocular pressure rise. Visual prognosis is good, especially in patients who have only anterior uveitis without corneal disease. PMID:20857175

  14. Comparison of clinical features between primary and drug-induced sleep-related eating disorder

    PubMed Central

    Komada, Yoko; Takaesu, Yoshikazu; Matsui, Kentaro; Nakamura, Masaki; Nishida, Shingo; Kanno, Meri; Usui, Akira; Inoue, Yuichi

    2016-01-01

    Purpose The aim of this study was to ascertain the clinical characteristics of drug-induced sleep-related eating disorder (SRED). Patients and methods We retrospectively reviewed the medical records of 30 patients with primary SRED (without any comorbid sleep disorders and who were not taking any possible causative medications), and ten patients with drug-induced SRED (occurrence of SRED episodes after starting nightly medication of sedative drugs, which completely resolved after dose reduction or discontinuation of the sedatives). Results All patients with drug-induced SRED took multiple types of sedatives, such as benzodiazepines or benzodiazepine receptor agonists. Clinical features of drug-induced SRED compared with primary SRED were as follows: higher mean age of onset (40 years old in drug-induced SRED vs 26 years old in primary SRED), significantly higher rate of patients who had total amnesia during most of their SRED episodes (75.0% vs 31.8%), significantly lower rate of comorbidity of night eating syndrome (0% vs 63.3%), and significantly lower rate of history of sleepwalking (10.0% vs 46.7%). Increased doses of benzodiazepine receptor agonists may be responsible for drug-induced SRED. Conclusion The clinical features of drug-induced SRED were different from those of primary SRED, possibly reflecting differences in the underlying mechanisms between these two categories of SREDs. PMID:27307740

  15. Genomic Features of the Human Dopamine Transporter Gene and Its Potential Epigenetic States: Implications for Phenotypic Diversity

    SciTech Connect

    Shumay, E.; Shumay, E.; Fowler, J.S.; Volkow, N.D.

    2010-06-01

    Human dopamine transporter gene (DAT1 or SLC6A3) has been associated with various brain-related diseases and behavioral traits and, as such, has been investigated intensely in experimental- and clinical-settings. However, the abundance of research data has not clarified the biological mechanism of DAT regulation; similarly, studies of DAT genotype-phenotype associations yielded inconsistent results. Hence, our understanding of the control of the DAT protein product is incomplete; having this knowledge is critical, since DAT plays the major role in the brain's dopaminergic circuitry. Accordingly, we reevaluated the genomic attributes of the SLC6A3 gene that might confer sensitivity to regulation, hypothesizing that its unique genomic characteristics might facilitate highly dynamic, region-specific DAT expression, so enabling multiple regulatory modes. Our comprehensive bioinformatic analyzes revealed very distinctive genomic characteristics of the SLC6A3, including high inter-individual variability of its sequence (897 SNPs, about 90 repeats and several CNVs spell out all abbreviations in abstract) and pronounced sensitivity to regulation by epigenetic mechanisms, as evident from the GC-bias composition (0.55) of the SLC6A3, and numerous intragenic CpG islands (27 CGIs). We propose that this unique combination of the genomic features and the regulatory attributes enables the differential expression of the DAT1 gene and fulfills seemingly contradictory demands to its regulation; that is, robustness of region-specific expression and functional dynamics.

  16. Prenatally detected ureteropelvic junction obstruction: clinical features and associated urologic abnormalities.

    PubMed

    Karnak, Ibrahim; Woo, Lynn L; Shah, Shetal N; Sirajuddin, Arlene; Kay, Robert; Ross, Jonathan H

    2008-04-01

    Urologic congenital anomalies associated with ureteropelvic obstruction (UPJO) have been previously characterized; however, less data are available regarding these associations in a prenatally diagnosed population. A retrospective study was conducted to evaluate significant clinical features and urological anomalies associated with prenatally diagnosed UPJO. The records of 143 children with prenatally diagnosed hydronephrosis secondary to UPJO were retrospectively reviewed. The gender, side of obstruction, degree of hydronephrosis, associated clinical features, and urological anomalies were noted. Hundred and forty-three children (M/F = 2.7) with a total of 198 affected renal units (RU) presenting with unilateral (61%) or bilateral (39%) UPJO were enrolled. In cases of unilateral obstruction, the left side was affected in 60 children (68%). The grade of hydronephrosis was Grade 1 in 56 RU (28%), Grade 2 in 51 RU (26%), Grade 3 in 50 RU (25%) and Grade 4 in 41 RU (21%). Associated clinical features included prematurity (n = 7, 4.9%), twinning (n = 5, 3.5%) and presentation with renal failure (RF) (n = 2). Excluding contralateral UPJO, other urologic anomalies were encountered in 29 patients (20.3%). Associated vesicoureteral reflux (VUR) was encountered in 11 patients (7.7%, M/F = 2.7). Pyeloplasty was required more often in children with associated VUR (54.5 vs. 18.2%) (P = 0.01). Contralateral multicystic dysplastic kidney (MCDK) was encountered in six patients (M/F = 2), one of whom presented with RF. One child carried the diagnosis of Schinzel-Giedion syndrome (SGS), demonstrating severe developmental and neurological disorders and bilateral hydronephrosis. The more frequent occurrence of UPJO in males with predominantly left-sided location, association with VUR and MCDK, and increased frequency of bilaterality in our prenatally diagnosed patients were similar to historical reports. In addition, prematurity and twinning were independently associated with UPJO

  17. Nodding syndrome in Ugandan children—clinical features, brain imaging and complications: a case series

    PubMed Central

    Idro, Richard; Opoka, Robert Opika; Aanyu, Hellen T; Kakooza-Mwesige, Angelina; Piloya-Were, Theresa; Namusoke, Hanifa; Musoke, Sarah Bonita; Nalugya, Joyce; Bangirana, Paul; Mwaka, Amos Deogratius; White, Steven; Chong, Kling; Atai-Omoruto, Anne D; Mworozi, Edison; Nankunda, Jolly; Kiguli, Sarah; Aceng, Jane Ruth; Tumwine, James K

    2013-01-01

    Objectives Nodding syndrome is a devastating neurological disorder of uncertain aetiology affecting children in Africa. There is no diagnostic test, and risk factors and symptoms that would allow early diagnosis are poorly documented. This study aimed to describe the clinical, electrophysiological and brain imaging (MRI) features and complications of nodding syndrome in Ugandan children. Design Case series. Participants 22 children with nodding syndrome brought to Mulago National Referral Hospital for assessment. Outcome measures Clinical features, physical and functional disabilities, EEG and brain MRI findings and a staging system with a progressive development of symptoms and complications. Results The median age of symptom onset was 6 (range 4–10) years and median duration of symptoms was 8.5 (range 2–11) years. 16 of 22 families reported multiple affected children. Physical manifestations and complications included stunting, wasting, lip changes and gross physical deformities. The bone age was delayed by 2 (range 1–6) years. There was peripheral muscle wasting and progressive generalised wasting. Four children had nodding as the only seizure type; 18 in addition had myoclonic, absence and/or generalised tonic–clonic seizures developing 1–3 years after the onset of illness. Psychiatric manifestations included wandering, aggression, depression and disordered perception. Cognitive assessment in three children demonstrated profound impairment. The EEG was abnormal in all, suggesting symptomatic generalised epilepsy in the majority. There were different degrees of cortical and cerebellar atrophy on brain MRI, but no hippocampal changes. Five stages with worsening physical, EEG and brain imaging features were identified: a prodrome, the development of head nodding and cognitive decline, other seizure types, multiple complications and severe disability. Conclusions Nodding syndrome is a neurological disorder that may be characterised as probably

  18. Imaging features of primary anorectal gastrointestinal stromal tumors with clinical and pathologic correlation

    PubMed Central

    Koch, M.R.; Jagannathan, J.P.; Krajewski, K.M.; Raut, C.P.; Hornick, J.L.; Ramaiya, N.H.

    2012-01-01

    Abstract Purpose: To evaluate the imaging features of anorectal gastrointestinal stromal tumors (GISTs) with clinical and histopathologic correlation. Materials and methods: In this Institutional Review Board-approved, Health Insurance Portability and Accountability Act-compliant retrospective study, 16 patients (12 men; mean age 66 years (30–89 years)) with pathologically proven anorectal GISTs seen at our institution from January 2001 to July 2011 were identified. Electronic medical records were reviewed to obtain clinical data. Pretreatment imaging studies (computed tomography (CT) in 16 patients, magnetic resonance imaging (MRI) in 9 patients and fluorodeoxyglucose (FDG)-positron emission tomography (PET)/CT in 8 patients) were evaluated by 2 radiologists until consensus. The location, size and imaging features of the primary tumor and metastases at presentation, if any, were recorded, and correlated with clinical data and pathologic features (histologic type, presence of necrosis, mitotic activity, risk category, immunohistochemical profile). Results: The mean tumor size was 6.9 × 6.0 cm. Of the 16 tumors, 11 (68.7%) were infralevator, 4 (25%) supra and infralevator and 1 (6.3%) supralevator; 9 (56.2%) were exophytic, 6 (37.5%) both exophytic and intraluminal, and 1 (6.3%) was intraluminal. The tumors were iso- to minimally hypoattenuating to muscle on CT, iso- to minimally hypointense on T1-weighted images, hyperintense on T2-weighted images and showed variable enhancement. Necrosis was seen in 4 (25%), and hemorrhage and calcification in 2 (12.5%) patients each. The tumors were FDG avid with a mean maximum standardized uptake value of 11 (8.4–16.8). All tumors were positive for KIT and CD34. Distant metastasis to liver was seen in 1 patient (6.3%) at presentation. Conclusion: Anorectal GISTs are well-circumscribed, non-circumferential, predominantly infralevator, intramural or exophytic, FDG-avid, hypoattenuating masses, and present without

  19. Homozygous N540K hypochondroplasia--first report: radiological and clinical features.

    PubMed

    De Rosa, M Laura Garcia; Fano, Virginia; Araoz, H Verónica; Chertkoff, Lilien; Obregon, M Gabriela

    2014-07-01

    We describe a 16-month-old male with N540K homozygous mutation in the FGFR3 gene who showed a more severe phenotype than hypochondroplasia (HCH). To our knowledge, a homozygous state for this mutation causing HCH has not been reported before. The clinical and radiological characteristics of our patient represent an intermediate condition between achondroplasia and achondroplasia/hypochondroplasia compound heterozygosity. This case represents a new expression of FGFR3 spectrum and it is of considerable importance for the genetic counseling in cases where both parents are affected with HCH. PMID:24715719

  20. Lipid-Rich Carcinoma of the Breast With Unusual Clinical and Histopathological Features.

    PubMed

    Gaspar, Balan Louis; Kumar, Mukin; Gupta, Rahul; Garg, Rashi; Singh, Rajinder; Vasishta, Rakesh Kumar

    2016-09-01

    Lipid-rich carcinoma of the breast is a rare form of invasive breast carcinoma of special type. Most cases are grade 3, hormone receptor negative, and associated with aggressive clinical behavior. We report an unusual case of lipid-rich carcinoma with morphological and immunophenotypical features different from those of cases reported so far in the literature. The index case underscores the fact that there is no consensus with regard to the exact nature of this tumor. Hence, larger studies are needed to draw meaningful conclusions. PMID:26920701

  1. Neuroleptic-induced Parkinson's syndrome: clinical features and results of treatment with levodopa.

    PubMed Central

    Hardie, R J; Lees, A J

    1988-01-01

    Twenty six consecutive patients with neuroleptic-induced Parkinson's syndrome (NIPS) are described. Their median age was 61 years, 60% were female, and most had received chronic neuroleptic medication for psychiatric indications. The clinical features were indistinguishable from idiopathic Parkinson's disease, except for the presence of co-existing orofacial chorea, limb dyskinesia or akathisia which provided an aetiological clue in 11 cases. Complete resolution of NIPS occurred in only two patients, one of whom later developed Parkinson's disease. Sixteen patients were treated with 300-1000 mg levodopa/benserazide for up to 4 years with few adverse effects but therapeutic response was disappointing. PMID:2900293

  2. Multiple system atrophy presenting as parkinsonism: clinical features and diagnostic criteria.

    PubMed Central

    Albanese, A; Colosimo, C; Bentivoglio, A R; Fenici, R; Melillo, G; Colosimo, C; Tonali, P

    1995-01-01

    To evaluate the possibility that parkinsonian signs may be the only presenting feature of multiple system atrophy (MSA), parkinsonian patients were studied who had no atypical clinical signs and had no symptoms of autonomic dysfunction, but who reported that they had not experienced the anticipated good response to dopaminergic treatment. These stringent criteria identified 20 patients from a series of 298 consecutive parkinsonian outpatients. The following clinical pointers were analysed: (a) rate of disease progression; (b) symmetry of parkinsonian symptoms and signs; (c) occurrence of resting tremor during the first three years from onset. In addition, all patients underwent (d) acute and chronic challenge with dopaminergic drugs; (e) cardiovascular reflex autonomic function tests; (f) high field MRI. Rapid progression of disease was seen in 45% of patients, onset was symmetric in 25%, tremor was absent at onset in 70%, response to dopaminergic drug challenges was inadequate in 40%, abnormal cardiovascular reflexes occurred in 50%, and some abnormal MRI finding occurred in 35% of cases. Each of these features was equally weighted by giving to each patient a 0 to 6 point score corresponding to the number of abnormal findings. Fifteen patients scoring higher than 1 were considered at risk for having MSA: five of them were classified as clinically possible (score 2), six as clinically probable (score 3-4), and four patients were classified as clinically definite multiple system atrophy (score 5). The six pointers considered were variably combined in each patient, none of them being universally abnormal in patients with high scores. The patients were followed up for a mean 2.1 (SEM 0.65) years. All but one of the 10 patients prospectively classified as probable or definite MSA developed unequivocal clinical signs of fully symptomatic MSA. A receiver operator characteristic cure was plotted for the prospective score based on follow up diagnosis. The best compromise

  3. Clinical and Dermoscopic Features of 88 Scalp Nevi in 39 Children

    PubMed Central

    Tcheung, W.J.; Bellet, J.S.; Prose, N.S.; Cyr, D.D.; Nelson, K.C.

    2011-01-01

    Summary Background Paediatric scalp nevi may represent a source of anxiety for practitioners and parents, as the clinical and dermoscopic features of typical nevi have yet to be defined. Prompted by concern about the large size, irregular borders, and colour variation of scalp nevi, clinicians and parents may request unnecessary excision of these nevi. Objective The purpose of this study is to establish the typical clinical and dermoscopic patterns of scalp nevi in children younger than 18 years old to help optimize clinical care and management. Methods Scalp nevi were imaged with a camera (Canon Rebel, XSi) and dermoscopic attachment (3Gen, Dermlite Foto, 30mm lens) to the camera. The clinical and dermoscopic images were reviewed and analyzed. Both acquired and congenital scalp nevi were included but were not further differentiated from each other. Results We obtained clinical and dermoscopic images of 88 scalp nevi in 39 Caucasian children. Two subjects had received chronic immunosuppressive medication. Nineteen children have had a family history of melanoma. Males (18/39 subjects, 46%) possessed 68% (60 nevi) of scalp nevi imaged. Younger (<10 years old) subjects (24/39 subjects, 62%) possessed 42% (37 nevi) of scalp nevi. The main clinical patterns included eclipse (n=18), cockade (n=3), solid brown (n=42), and solid pink (n=25) nevi. Solid-coloured nevi showed the following dermoscopic patterns: globular (57%), complex (reticular-globular) (27%), reticular (9%), homogenous (6%), and fibrillar (1%). The majority of nevi had a unifying feature—perifollicular hypopigmentation, which caused the appearance of scalloped, irregular borders if occurring on the periphery, or variegation in pigmentation, if occurring within the nevi. Conclusions Older subjects and males tend to harbour a larger proportion of scalp nevi. The main clinical patterns include solid-coloured and eclipse nevi. The most common dermoscopic pattern of scalp nevi is the globular pattern

  4. Wernicke's encephalopathy in a malnourished surgical patient: clinical features and magnetic resonance imaging.

    PubMed

    Nolli, M; Barbieri, A; Pinna, C; Pasetto, A; Nicosia, F

    2005-11-01

    We report a clinical and neuroradiological description of a severe case of Wernicke's encephalopathy in a surgical patient. After colonic surgery for neoplasm, he was treated for a long time with high glucose concentration total parenteral nutrition. In the early post-operative period, the patient showed severe encephalopathy with ataxia, ophthalmoplegia and consciousness disorders. We used magnetic resonance imaging (MRI) to confirm the clinical suspicion of Wernicke's encephalopathy. The radiological feature showed hyperintense lesions which were symmetrically distributed along the bulbo-pontine tegmentum, the tectum of the mid-brain, the periacqueductal grey substance, the hypothalamus and the medial periventricular parts of the thalamus. This progressed to typical Wernicke-Korsakoff syndrome with ataxia and memory and cognitive defects. Thiamine deficiency is a re-emerging problem in non-alcoholic patients and it may develop in surgical patients with risk factors such as malnutrition, prolonged vomiting and long-term high glucose concentration parenteral nutrition. PMID:16223408

  5. Clinical and microbiological features of Haemophilus influenzae vulvovaginitis in young girls

    PubMed Central

    Cox, R A; Slack, M P E

    2002-01-01

    Aims: To define the clinical and microbiological features of vulvovaginitis in prepubertal girls whose genital swabs yielded Haemophilus influenzae. Methods: Laboratory based study and retrospective collection of clinical data from the requesting doctors. Results: Thirty eight isolates of non-capsulate Haemophilus influenzae and one of H parainfluenzae were isolated from 32 girls aged 18 months to 11 years. No other pathogens, such as β haemolytic streptococci or yeasts, were present with H influenzae. The most common biotype was biotype II, comprising 57% of the 26 isolates biotyped. Six children had more than one episode of vulvovaginitis caused by H influenzae and a total of 14 children had recurrent vaginal symptoms. Conclusion: Children who have H influenzae vulvovaginitis are at risk of recurrent symptoms. Biotype II is the one most commonly associated with this condition. PMID:12461068

  6. Investigation of the clinical features in filamentary keratitis in Hangzhou, east of China

    PubMed Central

    Chen, Siming; Ruan, Yimeng; Jin, Xiuming

    2016-01-01

    Abstract Filamentary keratitis (FK) is a chronic and recurrent disorder of the cornea. FK is reportedly associated with various kinds of ocular surface diseases or conditions. Until now, there have been lacks of studies based on quantitative sample analysis concerning FK incidence regularity and inducement characteristics at different ages. This was a retrospective study of 147 patients (162 eyes) with FK who had been continuously and completely recorded from August 2012 to August 2015 at the Second Affiliated Hospital of Zhejiang University in Hangzhou, east of China. Our results suggest that the causative factors of FK varied at different ages and the distribution of filaments on the corneal surface was also diverse with different inducements. By exploring the frequency and clinical features of FK, we believe that the findings from our research will be clinically significant and aid in the early prevention and treatment guidance of the disease. PMID:27583881

  7. Clinical features of pulmonary artery sarcoma: A report of three cases

    PubMed Central

    Zhu, Guangfa; Pu, Xin; Guo, Hongjuang; Huang, Xiaoyong; Chen, Dong; Gan, Huili

    2016-01-01

    Pulmonary artery sarcoma (PAS) is a rare and highly malignant tumor of pulmonary artery origin. Since 1923, when the first case was reported, <300 cases have been reported worldwide. PAS has a poor prognosis, and early diagnosis with radical surgical resection offers patients with PAS the only chance of survival. However, due to its rarity and the non-specificity of its clinical manifestations and imaging presentation, PAS is frequently misdiagnosed as a pulmonary thromboembolic disease, including pulmonary thromboembolism (PTE) and chronic thromboembolic pulmonary hypertension (CTEPH). The present study reports three cases of PAS that were initially misdiagnosed as PTE or CTEPH, and were later shown to be PAS following surgery. In addition, the clinical features of these patients are examined in order to improve the differential diagnosis of PAS during the early stages of the disease, when the prognosis of patients with PAS is at its optimum. PMID:27446344

  8. Investigation of the clinical features in filamentary keratitis in Hangzhou, east of China.

    PubMed

    Chen, Siming; Ruan, Yimeng; Jin, Xiuming

    2016-08-01

    Filamentary keratitis (FK) is a chronic and recurrent disorder of the cornea. FK is reportedly associated with various kinds of ocular surface diseases or conditions. Until now, there have been lacks of studies based on quantitative sample analysis concerning FK incidence regularity and inducement characteristics at different ages. This was a retrospective study of 147 patients (162 eyes) with FK who had been continuously and completely recorded from August 2012 to August 2015 at the Second Affiliated Hospital of Zhejiang University in Hangzhou, east of China. Our results suggest that the causative factors of FK varied at different ages and the distribution of filaments on the corneal surface was also diverse with different inducements.By exploring the frequency and clinical features of FK, we believe that the findings from our research will be clinically significant and aid in the early prevention and treatment guidance of the disease. PMID:27583881

  9. Identification of landscape features influencing gene flow: How useful are habitat selection models?

    PubMed

    Roffler, Gretchen H; Schwartz, Michael K; Pilgrim, Kristy L; Talbot, Sandra L; Sage, George K; Adams, Layne G; Luikart, Gordon

    2016-07-01

    Understanding how dispersal patterns are influenced by landscape heterogeneity is critical for modeling species connectivity. Resource selection function (RSF) models are increasingly used in landscape genetics approaches. However, because the ecological factors that drive habitat selection may be different from those influencing dispersal and gene flow, it is important to consider explicit assumptions and spatial scales of measurement. We calculated pairwise genetic distance among 301 Dall's sheep (Ovis dalli dalli) in southcentral Alaska using an intensive noninvasive sampling effort and 15 microsatellite loci. We used multiple regression of distance matrices to assess the correlation of pairwise genetic distance and landscape resistance derived from an RSF, and combinations of landscape features hypothesized to influence dispersal. Dall's sheep gene flow was positively correlated with steep slopes, moderate peak normalized difference vegetation indices (NDVI), and open land cover. Whereas RSF covariates were significant in predicting genetic distance, the RSF model itself was not significantly correlated with Dall's sheep gene flow, suggesting that certain habitat features important during summer (rugged terrain, mid-range elevation) were not influential to effective dispersal. This work underscores that consideration of both habitat selection and landscape genetics models may be useful in developing management strategies to both meet the immediate survival of a species and allow for long-term genetic connectivity. PMID:27330556

  10. Identification of landscape features influencing gene flow: How useful are habitat selection models?

    USGS Publications Warehouse

    Roffler, Gretchen H.; Schwartz, Michael K.; Pilgrim, Kristy L.; Talbot, Sandra; Sage, Kevin; Adams, Layne G.; Luikart, Gordon

    2016-01-01

    Understanding how dispersal patterns are influenced by landscape heterogeneity is critical for modeling species connectivity. Resource selection function (RSF) models are increasingly used in landscape genetics approaches. However, because the ecological factors that drive habitat selection may be different from those influencing dispersal and gene flow, it is important to consider explicit assumptions and spatial scales of measurement. We calculated pairwise genetic distance among 301 Dall's sheep (Ovis dalli dalli) in southcentral Alaska using an intensive noninvasive sampling effort and 15 microsatellite loci. We used multiple regression of distance matrices to assess the correlation of pairwise genetic distance and landscape resistance derived from an RSF, and combinations of landscape features hypothesized to influence dispersal. Dall's sheep gene flow was positively correlated with steep slopes, moderate peak normalized difference vegetation indices (NDVI), and open land cover. Whereas RSF covariates were significant in predicting genetic distance, the RSF model itself was not significantly correlated with Dall's sheep gene flow, suggesting that certain habitat features important during summer (rugged terrain, mid-range elevation) were not influential to effective dispersal. This work underscores that consideration of both habitat selection and landscape genetics models may be useful in developing management strategies to both meet the immediate survival of a species and allow for long-term genetic connectivity.

  11. Distinguishing malaria and influenza: Early clinical features in controlled human experimental infection studies☆

    PubMed Central

    Lillie, Patrick J.; Duncan, Christopher J.A.; Sheehy, Susanne H.; Meyer, Joel; O'Hara, Geraldine A.; Gilbert, Sarah C.; Hill, Adrian V.S.

    2012-01-01

    Summary During the H1N1 influenza pandemic (pH1N1/09) diagnostic algorithms were developed to guide antiviral provision. However febrile illnesses are notoriously difficult to distinguish clinically. Recent evidence highlights the importance of incorporating travel history into diagnostic algorithms to prevent the catastrophic misdiagnosis of life-threatening infections such as malaria. We applied retrospectively the UK pH1N1/09 case definition to a unique cohort of healthy adult volunteers exposed to Plasmodium falciparum malaria or influenza to assess the predictive value of this case definition, and to explore the distinguishing clinical features of early phase infection with these pathogens under experimental conditions. For influenza exposure the positive predictive value of the pH1N1/09 case definition was only 0.38 (95% CI: 0.06–0.60), with a negative predictive value of 0.27 (95% CI: 0.02–0.51). Interestingly, 8/11 symptomatic malaria-infected adults would have been inappropriately classified with influenza by the pH1N1/09 case definition, while 5/8 symptomatic influenza-exposed volunteers would have been classified without influenza (P = 0.18 Fisher's exact). Cough (P = 0.005) and nasal symptoms (P = 0.001) were the only clinical features that distinguished influenza-exposed from malaria-exposed volunteers. An open mind regarding the clinical cause of undifferentiated febrile illness, particularly in the absence of upper respiratory tract symptoms, remains important even during influenza pandemic settings. These data support incorporating travel history into pandemic algorithms. PMID:22531678

  12. Clinical Features of Patients with Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorders

    PubMed Central

    Chen, Hai; Liu, Shi-Meng; Zhang, Xu-Xiang; Liu, Ya-Ou; Li, Si-Zhao; Liu, Zheng; Dong, Hui-Qing

    2016-01-01

    Background: Neuromyelitis optica spectrum disorder (NMOSD) was long believed to be an aggressive form of multiple sclerosis (MS). This study aimed to describe the clinical features of patients with MS and NMOSD to assist in differential diagnoses in clinical practice. Methods: Data including the patients’ serum and cerebrospinal fluid (CSF) tests, image findings, and clinical information from 175 patients with MS or NMOSD at Xuanwu Hospital, Capital Medical University from November 2012 to May 2014 were collected and analyzed retrospectively. An enzyme-linked immunosorbent assay was performed to detect the myelin oligodendrocyte glycoprotein (MOG) autoantibodies in CSF and serum. Cell-based assays were used to detect aquaporin-4-antibody (AQP4-Ab). The Chi-square test was used to compare the categorical variables. Wilcoxon rank sum test was performed to analyze the continuous variables. Results: Totally 85 MS patients (49%) and 90 NMOSD patients (51%) were enrolled, including 124 (71%) women and 51 (29%) men. Fewer MS patients (6%) had autoimmune diseases compared to NMOSD (19%) (χ2 = 6.9, P < 0.01). Patients with NMOSD had higher Expanded Disability Status Scale scores (3.5 [3]) than MS group (2 [2]) (Z = −3.69, P < 0.01). The CSF levels of white cell count and protein in both two groups were slightly elevated than the normal range, without significant difference between each other. Positivity of serum AQP4-Ab in NMOSD patients was higher than that in MS patients (MS: 0, NMOSD: 67%; χ2 = 63.9, P < 0.01). Oligoclonal bands in CSF among NMOSD patients were remarkably lower than that among MS (MS: 59%, NMOSD: 20%; χ2 = 25.7, P < 0.01). No significant difference of MOG autoantibodies was found between the two groups. Conclusion: The different CSF features combined with clinical, magnetic resonance imaging, and serum characteristics between Chinese patients with MS and NMOSD could assist in the differential diagnosis. PMID:27569235

  13. Clinical Features of Bacterial Vaginosis in a Murine Model of Vaginal Infection with Gardnerella vaginalis

    PubMed Central

    Gilbert, Nicole M.; Lewis, Warren G.; Lewis, Amanda L.

    2013-01-01

    Bacterial vaginosis (BV) is a dysbiosis of the vaginal flora characterized by a shift from a Lactobacillus-dominant environment to a polymicrobial mixture including Actinobacteria and Gram-negative bacilli. BV is a common vaginal condition in women and is associated with increased risk of sexually transmitted infection and adverse pregnancy outcomes such as preterm birth. Gardnerella vaginalis is one of the most frequently isolated bacterial species in BV. However, there has been much debate in the literature concerning the contribution of G. vaginalis to the etiology of BV, since it is also present in a significant proportion of healthy women. Here we present a new murine vaginal infection model with a clinical isolate of G. vaginalis. Our data demonstrate that this model displays key features used clinically to diagnose BV, including the presence of sialidase activity and exfoliated epithelial cells with adherent bacteria (reminiscent of clue cells). G. vaginalis was capable of ascending uterine infection, which correlated with the degree of vaginal infection and level of vaginal sialidase activity. The host response to G. vaginalis infection was characterized by robust vaginal epithelial cell exfoliation in the absence of histological inflammation. Our analyses of clinical specimens from women with BV revealed a measureable epithelial exfoliation response compared to women with normal flora, a phenotype that, to our knowledge, is measured here for the first time. The results of this study demonstrate that G. vaginalis is sufficient to cause BV phenotypes and suggest that this organism may contribute to BV etiology and associated complications. This is the first time vaginal infection by a BV associated bacterium in an animal has been shown to parallel the human disease with regard to clinical diagnostic features. Future studies with this model should facilitate investigation of important questions regarding BV etiology, pathogenesis and associated complications

  14. Comparison between type-2 and type-1 myocardial infarction: clinical features, treatment strategies and outcomes

    PubMed Central

    López-Cuenca, Angel; Gómez-Molina, Miriam; Flores-Blanco, Pedro J; Sánchez-Martínez, Marianela; García-Narbon, Andrea; De Las Heras-Gómez, Ignacio; Sánchez-Galian, María J; Guerrero-Pérez, Esther; Valdés, Mariano; Manzano-Fernández, Sergio

    2016-01-01

    Objective To assess the differences in incidence, clinical features, current treatment strategies and outcome in patients with type-2 vs. type-1 acute myocardial infarction (AMI). Methods We included 824 consecutive patients with a diagnosis of type-1 or type-2 AMI. During index hospitalization, clinical features and treatment strategies were collected in detail. At 1-year follow-up, mortality, stroke, non-fatal myocardial infarction and major bleeding were recorded. Results Type-1 AMI was present in 707 (86%) of the cases while 117 (14%) were classified as type-2. Patients with type-2 AMI were more frequently female and had higher co-morbidities such as diabetes, previous non-ST segment elevation acute coronary syndromes, impaired renal function, anaemia, atrial fibrillation and malignancy. However, preserved left ventricular ejection fraction and normal coronary arteries were more frequently seen, an invasive treatment was less common, and anti-platelet medications, statins and beta-blockers were less prescribed in patients with type-2 AMI. At 1-year follow-up, type-2 AMI was associated with a higher crude mortality risk (HR: 1.75, 95% CI: 1.14–2.68; P = 0.001), but this association did not remain significant after multivariable adjustment (P = 0.785). Furthermore, we did not find type-2 AMI to be associated with other clinical outcomes. Conclusions In this real-life population, compared with type-1, type-2 AMI were predominantly women and had more co-morbidities. Invasive treatment strategies and cardioprotective medications were less used in type-2, while the 1-year clinical outcomes were similar. PMID:26918008

  15. Molecular insight into the viral biology and clinical features of trichodysplasia spinulosa.

    PubMed

    Wu, J H; Nguyen, H P; Rady, P L; Tyring, S K

    2016-03-01

    Trichodysplasia spinulosa (TS) is a disfiguring skin disease that occurs most frequently in patients receiving immunosuppressive therapies, and is thus frequently associated with organ transplantation. TS is characterized clinically by folliculocentric papular eruption, keratin spine formation and development of leonine face; and histologically by expansion of the inner root sheath epithelium and high expression of the proliferative marker Ki-67. Recent discovery of the TS-associated polyomavirus (TSPyV) and emerging studies demonstrating the role of TSPyV tumour antigens in cell proliferation pathways have opened a new corridor for research on TS. In this brief review, we summarize the clinical and histological features of TS and evaluate the current options for therapy. Furthermore, we address the viral aetiology of the disease and explore the mechanisms by which TSPyV may influence TS development and progression. As reports of TS continue to rise, clinician recognition of TS, as well as accompanying research on its underlying pathogenesis and therapeutic options, is becoming increasingly important. It is our hope that heightened clinical suspicion for TS will increase rates of diagnosis and will galvanize both molecular and clinical interest in this disease. PMID:26479880

  16. The relevance of clinical and radiographic features of jaw lesions: A prospective study.

    PubMed

    Araujo, Juliane Piragine; Lemos, Celso Augusto; Miniello, Thais Gimenez; Alves, Fabio Abreu

    2016-01-01

    The study was carried out in a Brazilian population and the aim was to describe the prevalence and the clinic-radiographical features of jaw lesions. In addition, a comparison between the main diagnosis hypothesis and final diagnosis was accessed. A prospective study which evaluated all patients with jaw lesions diagnosed in an Oral Diagnosis Center, between August 2013 and October 2014. A total of 450 patients were observed for the first time, and 130 had some type of jaw lesion. The mean age of the patients was 35.2 years ± 17.86. Among these, 71 were women (54.62%) and 87 were Caucasian (66.92%). The mandible was affected more frequently (71.43%) than the maxilla (28.57%). Swelling and pain were the most frequent clinical signs and symptoms and were observed in 60 (42.85%) and 38 (27.14%) cases, respectively. The panoramic x-ray was the main radiographic exam utilized (88.57%). Radiolucent lesions accounted for 89 cases (63.57%) and the unilocular form was present in 114 cases (81.43%). A total of 93 cases had histopathological analyses and the periapical cyst was the most frequent lesion. In the other 47 lesions, the diagnosis was conducted by clinical and radiographic management. Bone lesions were frequent, being noted on first visit in approximately 30% of patients; in 1/3 of the cases, the diagnoses were completed with a combination of clinical and radiographic exams. PMID:27556683

  17. 30-Day Mortality in Acute Pulmonary Embolism: Prognostic Value of Clinical Scores and Anamnestic Features

    PubMed Central

    Bach, Andreas Gunter; Taute, Bettina-Maria; Baasai, Nansalmaa; Wienke, Andreas; Meyer, Hans Jonas; Schramm, Dominik; Surov, Alexey

    2016-01-01

    Purpose Identification of high-risk patients with pulmonary embolism is vital. The aim of the present study was to examine clinical scores, their single items, and anamnestic features in their ability to predict 30-day mortality. Materials and Methods A retrospective, single-center study from 06/2005 to 01/2010 was performed. Inclusion criteria were presence of pulmonary embolism, availability of patient records and 30-day follow-up. The following clinical scores were calculated: Acute Physiology and Chronic Health Evaluation II, original and simplified pulmonary embolism severity index, Glasgow Coma Scale, and euroSCORE II. Results In the study group of 365 patients 39 patients (10.7%) died within 30 days due to pulmonary embolism. From all examined scores and parameters the best predictor of 30-day mortality were the Glasgow Coma scale (≤ 10) and parameters of the circulatory system including presence of mechanical ventilation, arterial pH (< 7.335), and systolic blood pressure (< 99 mm Hg). Conclusions Easy to ascertain circulatory parameters have the same or higher prognostic value than the clinical scores that were applied in this study. From all clinical scores studied the Glasgow Coma Scale was the most time- and cost-efficient one. PMID:26866472

  18. Argyrophilic Grain Disease: Demographics, Clinical, and Neuropathological Features From a Large Autopsy Study.

    PubMed

    Rodriguez, Roberta Diehl; Suemoto, Claudia Kimie; Molina, Mariana; Nascimento, Camila Fernandes; Leite, Renata Elaine Paraizo; de Lucena Ferretti-Rebustini, Renata Eloah; Farfel, José Marcelo; Heinsen, Helmut; Nitrini, Ricardo; Ueda, Kenji; Pasqualucci, Carlos Augusto; Jacob-Filho, Wilson; Yaffe, Kristine; Grinberg, Lea Tenenholz

    2016-07-01

    Argyrophilic grain disease (AGD) is a frequent late-onset, 4-repeat tauopathy reported in Caucasians with high educational attainment. Little is known about AGD in non-Caucasians or in those with low educational attainment. We describe AGD demographics, clinical, and neuropathological features in a multiethnic cohort of 983 subjects ≥50 years of age from São Paulo, Brazil. Clinical data were collected through semistructured interviews with an informant and included in the Informant Questionnaire on Cognitive Decline in the Elderly, the Clinical Dementia Rating, and the Neuropsychiatric Inventory. Neuropathologic assessment relied on internationally accepted criteria. AGD was frequent (15.2%) and was the only neuropathological diagnosis in 8.9% of all cases (mean, 78.9 ± 9.4 years); it rarely occurred as an isolated neuropathological finding. AGD was associated with older age, lower socioeconomic status (SES), and appetite disorders. This is the first study of demographic, clinical, and neuropathological aspects of AGD in different ethnicities and subjects from all socioeconomic strata. The results suggest that prospective studies of AGD patients include levels of hormones related to appetite control as possible antemortem markers. Moreover, understanding the mechanisms behind higher susceptibility to AGD of low SES subjects may disclose novel environmental risk factors for AGD and other neurodegenerative diseases. PMID:27283329

  19. Kernelized partial least squares for feature reduction and classification of gene microarray data

    PubMed Central

    2011-01-01

    Background The primary objectives of this paper are: 1.) to apply Statistical Learning Theory (SLT), specifically Partial Least Squares (PLS) and Kernelized PLS (K-PLS), to the universal "feature-rich/case-poor" (also known as "large p small n", or "high-dimension, low-sample size") microarray problem by eliminating those features (or probes) that do not contribute to the "best" chromosome bio-markers for lung cancer, and 2.) quantitatively measure and verify (by an independent means) the efficacy of this PLS process. A secondary objective is to integrate these significant improvements in diagnostic and prognostic biomedical applications into the clinical research arena. That is, to devise a framework for converting SLT results into direct, useful clinical information for patient care or pharmaceutical research. We, therefore, propose and preliminarily evaluate, a process whereby PLS, K-PLS, and Support Vector Machines (SVM) may be integrated with the accepted and well understood traditional biostatistical "gold standard", Cox Proportional Hazard model and Kaplan-Meier survival analysis methods. Specifically, this new combination will be illustrated with both PLS and Kaplan-Meier followed by PLS and Cox Hazard Ratios (CHR) and can be easily extended for both the K-PLS and SVM paradigms. Finally, these previously described processes are contained in the Fine Feature Selection (FFS) component of our overall feature reduction/evaluation process, which consists of the following components: 1.) coarse feature reduction, 2.) fine feature selection and 3.) classification (as described in this paper) and prediction. Results Our results for PLS and K-PLS showed that these techniques, as part of our overall feature reduction process, performed well on noisy microarray data. The best performance was a good 0.794 Area Under a Receiver Operating Characteristic (ROC) Curve (AUC) for classification of recurrence prior to or after 36 months and a strong 0.869 AUC for

  20. Diversity of Meq gene from clinical Marek’s disease virus infection in Saudi Arabia

    PubMed Central

    Mohamed, Mahmoud H. A.; El-Sabagh, Ibrahim M.; Al-Habeeb, Malik A.; Al-Hammady, Yousef M.

    2016-01-01

    Aim: The aim of this study was to demonstrate the genomic features of Meq gene of Marek’s disease virus (MDV) recently circulating in Saudi Arabia (SA). Materials and Methods: Two poultry flocks suffering from mortalities and visceral tumors were presented to the Veterinary Teaching Hospital, King Faisal University, SA. Subjected to different diagnostic procedures: Case history, clinical signs, and necropsy as well as polymerase chain reaction followed by Meq gene sequence analysis. Results: Case history, clinical signs, and necropsy were suggestive of MDV infection. The Meq gene was successfully detected in liver and spleen of infected chickens. A 1062 bp band including the native Meq ORF in addition to a 939 bp of S-Meq (short isoform of Meq) were amplified from Saudi 01-13 and Saudi 02-13, respectively. The nucleotide and deduced amino acids sequences of the amplified Meq genes of both Saudi isolates showed distinct polymorphism when compared with the standard USA virulent isolates Md5 and GA. The sequence analysis of the S-Meq gene showed a 123 bp deletion representing 41 amino acids between two proline-rich areas without any frameshift. The Meq gene encoded four repeats of proline-rich repeats (PRRs sequences), whereas the S-Meq contains only two PRRs. Interestingly, the phylogenetic analysis revealed that both of SA MDV isolates are closely related to the MDV strains from Poland. Conclusion: The two MDV isolates contain several nucleotide polymorphisms resulting in distinct amino acid substitutions. It is suggested that migratory and wild birds, as well as world trading of poultry and its by-products, have a great contribution in the transmission of MDVs overseas. PMID:27397979

  1. Mechanism of PAP I gene induction during hepatocarcinogenesis: clinical implications.

    PubMed Central

    Dusetti, N. J.; Montalto, G.; Ortiz, E. M.; Masciotra, L.; Dagorn, J. C.; Iovanna, J. L.

    1996-01-01

    Pancreatitis-associated protein I (PAP I) is a secretory protein first described as an acute phase reactant during acute pancreatitis. Recently, induction of the PAP I gene was also described in liver during hepatocarcinogenesis. To investigate the molecular mechanisms of this induction, we used constructs carrying progressive deletions of the PAP I promoter fused to the CAT gene. We showed that the silencer conferring tissue specificity on the PAP I gene was inactive in hepatoma cells. Then, in an vitro transcription system, we compared the transcription capacity of nuclear extracts from normal liver and HepG2 cells on constructs containing the silencer. The results confirmed that a trans-acting factor interacting with the PAP I silencer was present in liver cells and absent from hepatoma cells. On the other hand, immunohistochemistry showed that PAP I was expressed in a limited number of transformed hepatocytes. It was concluded that expression of PAP I in hepatocarcinoma occurred through inactivation of its silencer element and was not concomitant in all malignant cells. On that basis, we assayed PAP I in serum from patients with chronic hepatitis, liver cirrhosis or hepatocarcinoma. PAP I levels were normal in chronic active or persistent hepatitis, significantly higher in cirrhosis and strongly elevated in hepatocarcinoma. Because those clinical entities often develop in that sequence, serum PAP I appeared as a potential marker of hepatocarcinoma development. Images Figure 3 Figure 4 Figure 5 PMID:8956791

  2. DNA Microarray Analysis in Screening Features of Genes Involved in Spinal Cord Injury.

    PubMed

    Liu, Yugang; Wang, Ying; Teng, Zhaowei; Zhang, Xiufeng; Ding, Min; Zhang, Zhaojun; Chen, Junli; Xu, Yanli

    2016-01-01

    BACKGROUND Spinal cord injury (SCI) is the most critical complication of spinal injury. We aimed to identify differentially expressed genes (DEGs) and to find associated pathways that may function as targets for SCI prognosis and therapy. MATERIAL AND METHODS Seven gene microarray expression profiles, downloaded from the GEO database (ID: GSE33886), were used to screen the DEGs of leg tissue and to compare these between SCI patients and corresponding normal specimens. Then, GO enrichment analysis was performed on these selected DEGs. Afterwards, interactions among these DEGs were analyzed by String database and then a PPI network was constructed to obtain topology character and modules in the PPI network. Finally, roles of the critical proteins in the pathway were explained by comparing the enrichment results of the genes in sub-modules and all the DEGs. RESULTS A total of 113 DEGs were determined. We found that 21 up-regulated genes were enriched in 7 biological processes, while 9 down-regulated genes were significantly enriched in 4 KEGG pathways. The PPI network was constructed, including 40 interacting genes and 73 interactions. Three obvious function modules were identified by exploring the PPI network, and ACTC1 was identified as the critical protein in the 3 enriched signal pathways. However, no obvious difference was found in the signal pathway in which both the 11 genes in module 1 and all 113 DEGs participated. CONCLUSIONS Core proteins in the signal pathway associated with spinal cord injury may serve as potential prognostic and predictive markers for the diagnosis and treatment of spinal cord injury in clinical applications. PMID:27160807

  3. DNA Microarray Analysis in Screening Features of Genes Involved in Spinal Cord Injury

    PubMed Central

    Liu, Yugang; Wang, Ying; Teng, Zhaowei; Zhang, Xiufeng; Ding, Min; Zhang, Zhaojun; Chen, Junli; Xu, Yanli

    2016-01-01

    Background Spinal cord injury (SCI) is the most critical complication of spinal injury. We aimed to identify differentially expressed genes (DEGs) and to find associated pathways that may function as targets for SCI prognosis and therapy. Material/Methods Seven gene microarray expression profiles, downloaded from the GEO database (ID: GSE33886), were used to screen the DEGs of leg tissue and to compare these between SCI patients and corresponding normal specimens. Then, GO enrichment analysis was performed on these selected DEGs. Afterwards, interactions among these DEGs were analyzed by String database and then a PPI network was constructed to obtain topology character and modules in the PPI network. Finally, roles of the critical proteins in the pathway were explained by comparing the enrichment results of the genes in sub-modules and all the DEGs. Results A total of 113 DEGs were determined. We found that 21 up-regulated genes were enriched in 7 biological processes, while 9 down-regulated genes were significantly enriched in 4 KEGG pathways. The PPI network was constructed, including 40 interacting genes and 73 interactions. Three obvious function modules were identified by exploring the PPI network, and ACTC1 was identified as the critical protein in the 3 enriched signal pathways. However, no obvious difference was found in the signal pathway in which both the 11 genes in module 1 and all 113 DEGs participated. Conclusions Core proteins in the signal pathway associated with spinal cord injury may serve as potential prognostic and predictive markers for the diagnosis and treatment of spinal cord injury in clinical applications. PMID:27160807

  4. Implementation of a classification hierarchy for the GeneTests/GeneClinics genetic testing databases.

    PubMed Central

    Edwards, J.; Tarczy-Hornoch, P.

    2002-01-01

    The combination of a) our changing understanding of genotypic and phenotypic classification of diseases and b) the rapid growth and expansion of the number of entries in two databases targeted toward clinicians resulted in the need to develop a flexible dynamic hierarchical classification system for genetic disorders. The two databases making use of this classification schemas are the GeneClinics (GC) database - www.geneclinics.org and the GeneTests (GT) database - www.genetests.org The GC and GT databases serve respsectively as the users manual and yellow pages of genetic testing. The GeneTests/GeneClinics (GT/GC) classification hierarchy is maintained as a simple set of parent/child relationships in a relational database. The hierarchy is generated in real time in response to a user request. It is not maintained as a set of members with relationships defined by characters that are parsed to determine the structure of the tree. The GT/GC classification hierarchy entries are handled as objects by the data maintenance and search tools and may have a number of attributes and associations that create a rich tool for defining and examining genetic disorders PMID:12463822

  5. [SOME CLINICAL AND CYTOKINE FEATURES OF THE CLINICAL COURSE OF RECURRENT RESPIRATORY SYSTEM DISEASES IN CHILDREN WITH THE TOXOCARIASIS INVASION].

    PubMed

    Dralova, A; Usachova, E

    2015-12-01

    The aim of the present study was to analyze clinical and cytokine features of recurrent respiratory system diseases in children with toxocariasis. 50 children aged 1 to 17 years (mean age - 10±5 years) with recurrent current of respiratory system disorders were studied. During the survey such clinical manifestations of the respiratory system disorders as obstructive bronchitis (50%), bronchial asthma (30%), pneumonia (10%) and laryngotracheitis (10%) have been revealed. Statistical analysis of the results was performed using the software package STATISTICA 6.1 (SNANSOFT). We have shown that the disorders of respiratory system in case of toxocariasis invasion often occur with severe intoxication and bronchial obstruction syndromes, temperature reaction, respiratory insufficiency and hepatomegaly. A prolonged course of the disease has been noted. "Inflammatory" indicators of general blood analysis, such as leukocytosis and increased of ESR have been recorded in patients with respiratory system disorders in children with T.canis infection significantly more often, significant "allergic" laboratory changes were in the form of eosinophilia. High average levels of pro-inflammatory IL-6, as well as low levels of IL 5 have been determined in children suffering from the respiratory system disorders and with toxocariasis invasion in the anamnesis. The obtained findings require further study. PMID:26719552

  6. Comparison of clinical features of HLA-Cw*0602-positive and -negative psoriasis patients in a Han Chinese population.

    PubMed

    Fan, Xing; Yang, Sen; Sun, Liang Dan; Liang, Yan Hua; Gao, Min; Zhang, Kai Yue; Huang, Wei; Zhang, XueJun

    2007-01-01

    HLA-Cw6 is strongly associated with psoriasis and has been suggested to be the PSORS1 gene that confers susceptibility to early-onset psoriasis. In this study of the clinical features of HLA-Cw*0602-positive and -negative psoriasis patients in a Han Chinese population, we typed HLA-C in a cohort of 679 patients and compared the two groups. Cw*0602-positive patients (n=345) had an earlier disease onset (p < 1 x 10(-5)), more severe disease (p < 1 x 10(-3)), higher frequency of guttate psoriasis (p < 1 x 10(-9)), more affected legs and trunk (p < 1 x 10(-5)), higher incidence of Köbner's phenomenon (p=0.005) and of trauma history (p=0.009). Cw*0602-negative patients (n= 334) had more palmoplantar pustulosis (p=0.004), nail changes (p=0.001) and scalp involvement (p=0.007). However, there was no statistically significant difference between the two groups regarding age, gender, incidence of plaque psoriasis, erythrodermic, inverse, psoriatic arthritis, and the precipitation factors stress and infection. The study showed that Cw*0602-positive patients had some obvious clinical differences from Cw*0602-negative patients in a Han Chinese population, which provides evidence for an HLA-Cw*0602-associated phenotype in psoriasis. PMID:17598037

  7. Clinical features of psychotic disorders and polymorphisms in HT2A, DRD2, DRD4, SLC6A3 (DAT1), and BDNF: a family based association study.

    PubMed

    Fanous, Ayman H; Neale, M C; Straub, R E; Webb, B T; O'Neill, A F; Walsh, D; Kendler, K S

    2004-02-15

    Schizophrenia is clinically heterogeneous and multidimensional, but it is not known whether this is due to etiological heterogeneity. Previous studies have not consistently reported association between any specific polymorphisms and clinical features of schizophrenia, and have primarily used case-control designs. We tested for the presence of association between clinical features and polymorphisms in the genes for the serotonin 2A receptor (HT2A), dopamine receptor types 2 and 4, dopamine transporter (SLC6A3), and brain-derived neurotrophic factor (BDNF). Two hundred seventy pedigrees were ascertained on the basis of having two or more members with schizophrenia or poor outcome schizoaffective disorder. Diagnoses were made using a structured interview based on the SCID. All patients were rated on the major symptoms of schizophrenia scale (MSSS), integrating clinical and course features throughout the course of illness. Factor analysis revealed positive, negative, and affective symptom factors. The program QTDT was used to implement a family-based test of association for quantitative traits, controlling for age and sex. We found suggestive evidence of association between the His452Tyr polymorphism in HT2A and affective symptoms (P = 0.02), the 172-bp allele of BDNF and negative symptoms (P = 0.04), and the 480-bp allele in SLC6A3 (= DAT1) and negative symptoms (P = 0.04). As total of 19 alleles were tested, we cannot rule out false positives. However, given prior evidence of involvement of the proteins encoded by these genes in psychopathology, our results suggest that more attention should be focused on the impact of these alleles on clinical features of schizophrenia. PMID:14755448

  8. Clinical Features and Outcome of Patients With IRAK-4 and MyD88 Deficiency

    PubMed Central

    Picard, Capucine; von Bernuth, Horst; Ghandil, Pegah; Chrabieh, Maya; Levy, Ofer; Arkwright, Peter D.; McDonald, Douglas; Geha, Raif S.; Takada, Hidetoshi; Krause, Jens C.; Creech, C. Buddy; Ku, Cheng-Lung; Ehl, Stephan; Maŕodi, Ĺaszĺo; Al-Muhsen, Saleh; Al-Hajjar, Sami; Al-Ghonaium, Abdulaziz; Day-Good, Noorbibi K.; Holland, Steven M.; Gallin, John; Chapel, Helen; Speert, David P.; Rodriguez-Gallego, Carlos; Colino, Elena; Garty, Ben-Zion; Roifman, Chaim; Hara, Toshiro; Yoshikawa, Hideto; Nonoyama, Shigeaki; Domachowske, Joseph; Issekutz, Andrew C.; Tang, Mimi; Smart, Joanne; Zitnik, Simona Eva; Hoarau, Cyrille; Kumararatne, Dinakantha; Thrasher, Adrian; Davies, E. Graham; Bethune, Claire; Sirvent, Nicolas; de Ricaud, Dominique; Camcioglu, Yildiz; Vasconcelos, J́ulia; Guedes, Margarida; Vitor, Artur Bonito; Rodrigo, Carlos; AlmaŸan, Francisco; Ḿendez, Maria; Aŕostegui, Juan Ignacio; Alsina, Laia; Fortuny, Claudia; Reichenbach, Janine; Verbsky, James W; Bossuyt, Xavier; Doffinger, Rainer; Abel, Laurent; Puel, Anne; Casanova, Jean-Laurent

    2011-01-01

    Autosomal recessive interleukin-1 receptor-associated kinase (IRAK)-4 and myeloid differentiation factor (MyD)88 deficiencies impair Toll-like receptor (TLR)- and interleukin-1 receptor-mediated immunity. We documented the clinical features and outcome of 48 patients with IRAK-4 deficiency and 12 patients with MyD88 deficiency, from 37 kindreds in 15 countries. The clinical features of IRAK-4 and MyD88 deficiency were indistinguishable. There were no severe viral, parasitic, and fungal diseases, and the range of bacterial infections was narrow. Noninvasive bacterial infections occurred in 52 patients, with a high incidence of infections of the upper respiratory tract and the skin, mostly caused by Pseudomonas aeruginosa and Staphylococcus aureus, respectively. The leading threat was invasive pneumococcal disease, documented in 41 patients (68%) and causing 72 documented invasive infections (52.2%). P. aeruginosa and Staph. aureus documented invasive infections also occurred (16.7% and 16%, respectively, in 25% and 25% of patients). Systemic signs of inflammation were usually weak or delayed. The first invasive infection occurred before the age of 2 years in 53 (88.3%) and in the neonatal period in 19 (32.7%) patients. Multiple or recurrent invasive infections were observed in most survivors (n = 36/50, 72%). PMID:21057262

  9. Familial deletion of 18p associated with Turner like clinical features

    SciTech Connect

    Say, B.; Gopal Rao, V.V.N.; Harris, S.

    1994-09-01

    The authors report the first occurrence to our knowledge of a familial deletion of the short arm of chromosome 18 in a mother and daughter. The proband is an 18-year-old female referred for chromosomal analysis because of mental retardation and short stature. She is the only offspring. Her birth weight was 3 pounds 10 ounces (below 5th percentile). As a child, she had delayed milestones. Her IQ is 69 and she is in classes for the educable mentally handicapped. Her height is 145.6 cm and weight 38.7 kg (both below 5th percentile). Physical examination revealed a low nuchal hairline. She has myopia. Chromosome analysis from peripheral blood lymphocytes revealed a 46,XX,del(18)(p11.21) karyotype. Since some of the same clinical features are also seen in the mother including short stature (157 cm), mental retardation, ocular problems like cataracts, exotropia and refractive error, chromosome analysis was performed which showed the same 46,XX,del(18)(p11.21) karyotype. A familial case like this has great implications in genetic counseling. Since the syndrome is not associated with sterility, the recurrence risk for the offspring is 50%. Patients with deletion (18p) syndrome are reported to have findings suggestive of Turner syndrome with varying degrees of mental retardation. We recommend that in patients with such clinical features associated with mental retardation, normal menstrual history and/or fertility, the possibility of deletion (18p) syndrome be considered.

  10. Clinical features of patients with Philadelphia-negative myeloproliferative neoplasms complicated by portal hypertension

    PubMed Central

    Yan, Matthew; Geyer, Holly; Mesa, Ruben; Atallah, Ehab; Callum, Jeannie; Bartoszko, Justyna; Yee, Karen; Maganti, Manjula; Wong, Florence; Gupta, Vikas

    2015-01-01

    Backgroud Portal hypertension (PHTN) has been reported to afflict 7-18% of patients with Philadelphia-negative myeloproliferative neoplasms (MPNs), with complications of variceal bleeding and ascites. The clinical features and outcomes of these patients are unclear. Patients and Methods In this multi-centre retrospective study, we evaluated the clinical features of 51 patients with MPNs complicated by PHTN. Results The diagnosis of underlying MPN was most frequently polycythemia vera (PV) (39%) and primary myelofibrosis (MF) (35%), followed by post-PV myelofibrosis (18%), essential thrombocythemia (ET) (4%) and post-ET myelofibrosis (4%). Frequency of JAK2 V617F mutation appears as expected in the underlying MPN. Thrombosis within the splanchnic circulation was prevalent in patients with polycythemia compared to other MPNs (76% vs. 26%, p=0.0007). Conclusions PV and MF patients have a higher incidence of PHTN in our population, with thrombosis contributing to PHTN development in PV patients. Patients with splanchnic circulation thrombosis are potential candidates for screening for portal hypertension. These data may be useful for developing screening strategies for early detection of PHTN in patients with MPN. PMID:25027569

  11. Clinical features and outcomes of idiopathic pulmonary alveolar proteinosis in Korean population.

    PubMed

    Byun, Min Kwang; Kim, Dong Soon; Kim, Young Whan; Chung, Man Pyo; Shim, Jae Jeong; Cha, Seung Ick; Uh, Soo-Taek; Park, Choon Sik; Jeong, Sung Hwan; Park, Yong Bum; Lee, Hong Lyeol; Park, Moo Suk

    2010-03-01

    Idiopathic pulmonary alveolar proteinosis (PAP) is a rare disorder in which lipoproteinaceous material accumulates within alveoli. There were few reports on Asian populations with idiopathic PAP. We retrospectively reviewed 38 patients with idiopathic PAP in Korea. We assessed clinical features, therapeutic efficacy and outcomes of whole lung lavage in patients with idiopathic PAP. The mean age at diagnosis was 52 yr. Eighty six percent of patients were symptomatic at diagnosis. Dyspnea and cough were the most common symptoms. Crackles were the most common physical examination finding. On pulmonary function test, a mild restrictive ventilatory defect was common, with a predicted mean forced vital capacity (FVC) of 77% and forced expiratory volume in one second (FEV(1)) of 84.6%. Diffusing capacity was disproportionately reduced at 67.7%. Arterial blood gas analysis revealed hypoxemia with a decreased PaO2 of 69.0 mmHg and an increased D(A-a)O2 of 34.2 mmHg. After whole lung lavage, PaO2, D(A-a)O2 and DL(CO) were significantly improved, but FVC and total lung capacity (TLC) were not different. This is the first multicenter study to analyze 38 Korean patients with idiopathic PAP. The clinical features and pulmonary parameters of Korean patients with idiopathic PAP are consistent with reports in other published studies. Whole lung lavage appears to be the most effective form of treatment. PMID:20191038

  12. Relationship between childhood adversity and clinical and cognitive features in schizophrenia.

    PubMed

    McCabe, Kathryn L; Maloney, Elizabeth A; Stain, Helen J; Loughland, Carmel M; Carr, Vaughan J

    2012-05-01

    Childhood adversity is associated with elevated risk for a wide range of adult psychiatric disorders, and has significant and sustained negative effects on adult behavioural and social functioning. Elevated rates of childhood adversity have been reported for people with a diagnosis of schizophrenia. The aim of the present study was to assess rates of retrospectively reported childhood adversity among adults with schizophrenia and to examine the relationship between childhood adversity and clinical and cognitive features. Data were available for 408 schizophrenia participants and 267 healthy control participants recruited through the Australian Schizophrenia Research Bank (ASRB). History of childhood adversity was obtained using the Childhood Adversity Questionnaire (CAQ). A five-factor solution was identified from the CAQ. Schizophrenia participants reported experiencing more childhood adversities than controls. In both groups, those reporting childhood adversity were more likely to be female and older. Among participants with schizophrenia, positive symptom severity and fewer years of education were associated with childhood adversity. Lower IQ scores and personality traits were associated with reporting a greater number of childhood adversities and with adversity sub-types of abusive, neglectful and dysfunctional parenting. The rate of childhood adversity reported in this sample was high which suggests greater exposure to adverse childhood events among participants with schizophrenia in comparison with healthy controls. We identified unique groups amongst CAQ items that provided a salient framework from which to investigate the connection between childhood adversity and clinical and cognitive features. PMID:22329951

  13. The Clinical Features and Bacteriological Characterizations of Bone and Joint Tuberculosis in China

    PubMed Central

    Chen, Su-Ting; Zhao, Li-Ping; Dong, Wei-Jie; Gu, Yun-Ting; Li, Yun-Xu; Dong, Ling-Ling; Ma, Yi-Feng; Qin, Shi-Bing; Huang, Hai-Rong

    2015-01-01

    Bone and Joint tuberculosis (BJTB) constitutes about 10% of total extra-pulmonary TB cases. Since the BJTB is a paucibacillary condition, there has been no systematic study on the bacterial characterization, especially the epidemiological feature. Here we collected the mycobacterial clinical isolates, analyzed the clinical features and the bacteriological characteristics from 113 BJTB cases reported in China. The mean age of the cases was 40.33 years while most of the patients fell into the 20–29 year age group; local pain was the most common onset symptom of BJTB cases; mean time from symptom onset to BJTB diagnosis was 13.16 months. 31 isolates were defined as drug resistant, including 15 multidrug resistant (MDR) and 2 extensively drug resistant (XDR) isolates according to the drug susceptibility test outcomes; after spoligotyping, 87.6% (99/113) isolates were categorized as Beijing family. In contrast to the isolates from pulmonary tuberculosis patients, here the MIRU-VNTR assay did not find anything significant. A prolonged time span for BJTB diagnosis highlights the requirement of paying further attention to BJTB infection in China. This study provides essential insights into the demographic and microbial characteristics of BJTB cases in China. PMID:26053666

  14. Trichophyton tonsurans infection in Japan: epidemiology, clinical features, diagnosis and infection control.

    PubMed

    Hiruma, Junichiro; Ogawa, Yumi; Hiruma, Masataro

    2015-03-01

    In this review, we summarize the status of Trichophyton tonsurans infection in Japan in terms of epidemiology, clinical features, diagnosis and infection control. Since approximately 2000, outbreaks of T. tonsurans infections among combat sports club members have been reported frequently, with the infection then spreading to their friends and family members. The most common clinical features of T. tonsurans infection are tinea corporis, which is difficult to differentiate from eczema, and tinea capitis. Tinea capitis is classified as the seborrheic form, kerion celsi form or "black dot" form, although 90% or more of patients are asymptomatic carriers. The diagnosis of symptomatic T. tonsurans infection is established by potassium hydroxide examination and fungal culture. However, because there are many asymptomatic carriers of T. tonsurans infection, tests using the hairbrush culture method are necessary. An increase in asymptomatic carriers of T. tonsurans makes assessment of the current prevalence of the infection challenging and underscores the importance of educational efforts and public awareness campaigns to prevent T. tonsurans epidemics. PMID:25736317

  15. Identifying the biting species in snakebite by clinical features: an epidemiological tool for community surveys.

    PubMed

    Pathmeswaran, A; Kasturiratne, A; Fonseka, M; Nandasena, S; Lalloo, D G; de Silva, H J

    2006-09-01

    The outcome of snakebite is related to the biting species but it is often difficult to identify the biting snake, particularly in community settings. We have developed a clinical scoring system suitable for use in epidemiological surveys, with the main aim of identifying the presumed biting species in those with systemic envenoming who require treatment. The score took into account ten features relating to bites of the five medically important snakes in Sri Lanka, and an algorithm was developed applying different weightings for each feature for different species. A systematically developed artificial data set was used to fine tune the score and to develop criteria for definitive identification. The score was prospectively validated using 134 species-confirmed snakebites. It correctly differentiated the bites caused by the three snakes that commonly cause major clinical problems (Russell's viper (RV), kraits and cobra) from other snakes (hump-nosed viper (HNV) and saw-scaled viper (SSV)) with 80% sensitivity and 100% specificity. For individual species, sensitivity and specificity were, respectively: cobra 76%, 99%; kraits 85%, 99%; and RV 70%, 99%. As anticipated, the score was insensitive in the identification of bites due to HNV and SSV. PMID:16412486

  16. THE RARE DISEASES CLINICAL RESEARCH NETWORK CONTACT REGISTRY UPDATE: FEATURES AND FUNCTIONALITY

    PubMed Central

    Richesson, Rachel; Sutphen, Rebecca; Shereff, Denise; Krischer, Jeff

    2013-01-01

    The Rare Diseases Clinical Research Network (RDCRN) Contact Registry has grown in size and scope since it was first reported in this journal in 2007. In this paper, we reflect on our seven years’ experience developing and expanding the RDCRN Contact Registry to include many more rare diseases. We present the functional and data requirements that motivated this registry, and the new features and policies that have been developed since. Given the high costs and long-term commitment required to build patient registries, the RDCRN Contact Registry experience represents a reasonable approach for identifying and cultivating potential research populations, with minimal resources and patient burden. The basic model of a patient-reported registry has not changed since our 2007 report, but the number of diseases has grown from 42 to 201, and the types of information that are exchanged with participants has expanded. A patient-directed information-sharing feature has been added to reduce barriers to communication between investigators and patients affected by rare and genetic diseases. As specific data and research needs arise, the Contact Registry can be leveraged to access needed data or to solicit patients for particular research opportunities. This multiple-disease registry is scalable, expandable, and standards-driven, and has become a model for clinical and translational research across rare and many other diseases. PMID:22405970

  17. Drivers of structural features in gene regulatory networks: From biophysical constraints to biological function.

    PubMed

    Martin, O C; Krzywicki, A; Zagorski, M

    2016-07-01

    Living cells can maintain their internal states, react to changing environments, grow, differentiate, divide, etc. All these processes are tightly controlled by what can be called a regulatory program. The logic of the underlying control can sometimes be guessed at by examining the network of influences amongst genetic components. Some associated gene regulatory networks have been studied in prokaryotes and eukaryotes, unveiling various structural features ranging from broad distributions of out-degrees to recurrent "motifs", that is small subgraphs having a specific pattern of interactions. To understand what factors may be driving such structuring, a number of groups have introduced frameworks to model the dynamics of gene regulatory networks. In that context, we review here such in silico approaches and show how selection for phenotypes, i.e., network function, can shape network structure. PMID:27365153

  18. Drivers of structural features in gene regulatory networks: From biophysical constraints to biological function

    NASA Astrophysics Data System (ADS)

    Martin, O. C.; Krzywicki, A.; Zagorski, M.

    2016-07-01

    Living cells can maintain their internal states, react to changing environments, grow, differentiate, divide, etc. All these processes are tightly controlled by what can be called a regulatory program. The logic of the underlying control can sometimes be guessed at by examining the network of influences amongst genetic components. Some associated gene regulatory networks have been studied in prokaryotes and eukaryotes, unveiling various structural features ranging from broad distributions of out-degrees to recurrent "motifs", that is small subgraphs having a specific pattern of interactions. To understand what factors may be driving such structuring, a number of groups have introduced frameworks to model the dynamics of gene regulatory networks. In that context, we review here such in silico approaches and show how selection for phenotypes, i.e., network function, can shape network structure.

  19. The clinical implications of gene mutations in chronic lymphocytic leukaemia.

    PubMed

    Rossi, Davide; Gaidano, Gianluca

    2016-04-12

    Chronic lymphocytic leukaemia (CLL) is a molecularly heterogeneous disease as revealed by recent genomic studies. Among genetic lesions that are recurrent in CLL, few clinically validated prognostic markers, such as TP53 mutations and 17p deletion, are available for the use in clinical practice to guide treatment decisions. Recently, several novel molecular markers have been identified in CLL. Though these mutations have not yet gained the qualification of predictive factors for treatment tailoring, they have shown to be promising to refine the prognostic stratification of patients. The introduction of targeted drugs is changing the genetics of CLL, and has disclosed the acquisition of previously unexpected drug resistant mutations in signalling pathway genes. Ultra-deep next generation sequencing has allowed to reach deep levels of resolution of the genetic portrait of CLL providing a precise definition of its subclonal genetic architecture. This approach has shown that small subclones harbouring drug resistant mutations anticipate the development of a chemorefractory phenotype. Here we review the recent advances in the definition of the genomic landscape of CLL and the ongoing research to characterise the clinical implications of old and new molecular lesions in the setting of both conventional chemo-immunotherapy and targeted drugs. PMID:27031852

  20. The clinical implications of gene mutations in chronic lymphocytic leukaemia

    PubMed Central

    Rossi, Davide; Gaidano, Gianluca

    2016-01-01

    Chronic lymphocytic leukaemia (CLL) is a molecularly heterogeneous disease as revealed by recent genomic studies. Among genetic lesions that are recurrent in CLL, few clinically validated prognostic markers, such as TP53 mutations and 17p deletion, are available for the use in clinical practice to guide treatment decisions. Recently, several novel molecular markers have been identified in CLL. Though these mutations have not yet gained the qualification of predictive factors for treatment tailoring, they have shown to be promising to refine the prognostic stratification of patients. The introduction of targeted drugs is changing the genetics of CLL, and has disclosed the acquisition of previously unexpected drug resistant mutations in signalling pathway genes. Ultra-deep next generation sequencing has allowed to reach deep levels of resolution of the genetic portrait of CLL providing a precise definition of its subclonal genetic architecture. This approach has shown that small subclones harbouring drug resistant mutations anticipate the development of a chemorefractory phenotype. Here we review the recent advances in the definition of the genomic landscape of CLL and the ongoing research to characterise the clinical implications of old and new molecular lesions in the setting of both conventional chemo-immunotherapy and targeted drugs. PMID:27031852

  1. Temporal and spatial dynamics of scaling-specific features of a gene regulatory network in Drosophila

    PubMed Central

    Wu, Honggang; Manu; Jiao, Renjie; Ma, Jun

    2015-01-01

    A widely appreciated aspect of developmental robustness is pattern formation in proportion to size. But how such scaling features emerge dynamically remains poorly understood. Here we generate a data set of the expression profiles of six gap genes in Drosophila melanogaster embryos that differ significantly in size. Expression patterns exhibit size-dependent dynamics both spatially and temporally. We uncover a dynamic emergence of under-scaling in the posterior, accompanied by reduced expression levels of gap genes near the middle of large embryos. Simulation results show that a size-dependent Bicoid gradient input can lead to reduced Krüppel expression that can have long-range and dynamic effects on gap gene expression in the posterior. Thus, for emergence of scaled patterns, the entire embryo may be viewed as a single unified dynamic system where maternally derived size-dependent information interpreted locally can be propagated in space and time as governed by the dynamics of a gene regulatory network. PMID:26644070

  2. A novel roseobacter phage possesses features of podoviruses, siphoviruses, prophages and gene transfer agents.

    PubMed

    Zhan, Yuanchao; Huang, Sijun; Voget, Sonja; Simon, Meinhard; Chen, Feng

    2016-01-01

    Bacteria in the Roseobacter lineage have been studied extensively due to their significant biogeochemical roles in the marine ecosystem. However, our knowledge on bacteriophage which infects the Roseobacter clade is still very limited. Here, we report a new bacteriophage, phage DSS3Φ8, which infects marine roseobacter Ruegeria pomeroyi DSS-3. DSS3Φ8 is a lytic siphovirus. Genomic analysis showed that DSS3Φ8 is most closely related to a group of siphoviruses, CbK-like phages, which infect freshwater bacterium Caulobacter crescentus. DSS3Φ8 contains a smaller capsid and has a reduced genome size (146 kb) compared to the CbK-like phages (205-279 kb). DSS3Φ8 contains the DNA polymerase gene which is closely related to T7-like podoviruses. DSS3Φ8 also contains the integrase and repressor genes, indicating its potential to involve in lysogenic cycle. In addition, four GTA (gene transfer agent) genes were identified in the DSS3Φ8 genome. Genomic analysis suggests that DSS3Φ8 is a highly mosaic phage that inherits the genetic features from siphoviruses, podoviruses, prophages and GTAs. This is the first report of CbK-like phages infecting marine bacteria. We believe phage isolation is still a powerful tool that can lead to discovery of new phages and help interpret the overwhelming unknown sequences in the viral metagenomics. PMID:27460944

  3. A novel roseobacter phage possesses features of podoviruses, siphoviruses, prophages and gene transfer agents

    NASA Astrophysics Data System (ADS)

    Zhan, Yuanchao; Huang, Sijun; Voget, Sonja; Simon, Meinhard; Chen, Feng

    2016-07-01

    Bacteria in the Roseobacter lineage have been studied extensively due to their significant biogeochemical roles in the marine ecosystem. However, our knowledge on bacteriophage which infects the Roseobacter clade is still very limited. Here, we report a new bacteriophage, phage DSS3Φ8, which infects marine roseobacter Ruegeria pomeroyi DSS-3. DSS3Φ8 is a lytic siphovirus. Genomic analysis showed that DSS3Φ8 is most closely related to a group of siphoviruses, CbK-like phages, which infect freshwater bacterium Caulobacter crescentus. DSS3Φ8 contains a smaller capsid and has a reduced genome size (146 kb) compared to the CbK-like phages (205–279 kb). DSS3Φ8 contains the DNA polymerase gene which is closely related to T7-like podoviruses. DSS3Φ8 also contains the integrase and repressor genes, indicating its potential to involve in lysogenic cycle. In addition, four GTA (gene transfer agent) genes were identified in the DSS3Φ8 genome. Genomic analysis suggests that DSS3Φ8 is a highly mosaic phage that inherits the genetic features from siphoviruses, podoviruses, prophages and GTAs. This is the first report of CbK-like phages infecting marine bacteria. We believe phage isolation is still a powerful tool that can lead to discovery of new phages and help interpret the overwhelming unknown sequences in the viral metagenomics.

  4. A novel roseobacter phage possesses features of podoviruses, siphoviruses, prophages and gene transfer agents

    PubMed Central

    Zhan, Yuanchao; Huang, Sijun; Voget, Sonja; Simon, Meinhard; Chen, Feng

    2016-01-01

    Bacteria in the Roseobacter lineage have been studied extensively due to their significant biogeochemical roles in the marine ecosystem. However, our knowledge on bacteriophage which infects the Roseobacter clade is still very limited. Here, we report a new bacteriophage, phage DSS3Φ8, which infects marine roseobacter Ruegeria pomeroyi DSS-3. DSS3Φ8 is a lytic siphovirus. Genomic analysis showed that DSS3Φ8 is most closely related to a group of siphoviruses, CbK-like phages, which infect freshwater bacterium Caulobacter crescentus. DSS3Φ8 contains a smaller capsid and has a reduced genome size (146 kb) compared to the CbK-like phages (205–279 kb). DSS3Φ8 contains the DNA polymerase gene which is closely related to T7-like podoviruses. DSS3Φ8 also contains the integrase and repressor genes, indicating its potential to involve in lysogenic cycle. In addition, four GTA (gene transfer agent) genes were identified in the DSS3Φ8 genome. Genomic analysis suggests that DSS3Φ8 is a highly mosaic phage that inherits the genetic features from siphoviruses, podoviruses, prophages and GTAs. This is the first report of CbK-like phages infecting marine bacteria. We believe phage isolation is still a powerful tool that can lead to discovery of new phages and help interpret the overwhelming unknown sequences in the viral metagenomics. PMID:27460944

  5. RPGR-associated retinopathy: clinical features, molecular genetics, animal models and therapeutic options.

    PubMed

    Tee, James J L; Smith, Alexander J; Hardcastle, Alison J; Michaelides, Michel

    2016-08-01

    Retinitis pigmentosa GTPase regulator (RPGR) gene sequence variants account for the vast majority of X linked retinitis pigmentosa (RP), which is one of the most severe forms of RP. Symptoms of nyctalopia typically begin in childhood, with increasing loss of peripheral visual field during teenage years, and progressive central visual loss during the second to fourth decade of life. There is however marked intrafamilial and interfamilial phenotypic heterogeneity in affected males and carrier females. There is now a far greater understanding of the range of phenotypes associated with variants in this gene; including rod-cone dystrophy, cone-rod dystrophy, cone dystrophy, macular dystrophy and non-ocular phenotypes. There are also increasingly established genotype-phenotype associations and structure-function correlations. RPGR is involved in ciliary function, with ciliary dysfunction now recognised as the mechanism underlying a large proportion of inherited retinal disease. There has been significant progress in identifying naturally occurring animal models and developing novel models to define the underlying disease mechanisms and to test gene replacement therapy, in addition to advances in human retinal imaging, culminating in completed and planned clinical trials. These significant developments will be discussed. PMID:26843488

  6. A series of Greek children with pure hereditary spastic paraplegia: clinical features and genetic findings.

    PubMed

    Polymeris, Alexandros A; Tessa, Alessandra; Anagnostopoulou, Katherine; Rubegni, Anna; Galatolo, Daniele; Dinopoulos, Argirios; Gika, Artemis D; Youroukos, Sotiris; Skouteli, Eleni; Santorelli, Filippo M; Pons, Roser

    2016-08-01

    Hereditary spastic paraplegia (HSP) is a clinically and genetically heterogeneous group of neurodegenerative disorders mainly characterized by progressive spasticity of the lower limbs. Adult case series dominate the literature, and there have been only a few studies in children. The purpose of this study is to describe our experience with pediatric HSP in Greece. We report the clinical and genetic findings in our patients and aim to offer insights into the diagnostic difficulties of childhood-onset disease. A series of 15 Greek children affected by pure HSP underwent extensive diagnostic investigations. Molecular analysis included whole exome sequencing (WES) or consecutive screening of candidate genes ATL1, SPAST, REEP1, and CYP7B1. WES performed in three cases yielded previously reported mutations in ATL1 and CYP7B1, and a variant c.397C>T of unknown significance in SPG7. Candidate gene screening performed in the remaining patients identified previously reported mutations in ATL1 (2), SPAST (2), and REEP1 (1), and two novel mutations, c.1636G>A and c.1413+3_6delAAGT, in SPAST. In six cases, the mutations were inherited from their parents, while in three cases, the mutations were apparently de novo. Our data confirm the genetic heterogeneity of childhood-onset pure HSP, with SPG4/SPAST and SPG3A/ATL1 being the most frequent forms. De novo occurrence of HSP does not seem to be uncommon. Candidate gene studies guided by diagnostic algorithms and WES seem both to be reasonable genetic testing strategies. PMID:27260292

  7. Clinical Features of Adult/Adolescent Atopic Dermatitis and Chinese Criteria for Atopic Dermatitis

    PubMed Central

    Liu, Ping; Zhao, Yan; Mu, Zhang-Lei; Lu, Qian-Jin; Zhang, Li; Yao, Xu; Zheng, Min; Tang, Yi-Wen; Lu, Xin-Xiang; Xia, Xiu-Juan; Lin, You-Kun; Li, Yu-Zhen; Tu, Cai-Xia; Yao, Zhi-Rong; Xu, Jin-Hua; Li, Wei; Lai, Wei; Yang, Hui-Min; Xie, Hong-Fu; Han, Xiu-Ping; Xie, Zhi-Qiang; Nong, Xiang; Guo, Zai-Pei; Deng, Dan-Qi; Shi, Tong-Xin; Zhang, Jian-Zhong

    2016-01-01

    Background: Atopic dermatitis (AD) is an inflammatory skin disease characterized by chronic recurrent dermatitis with profound itching. Most patients have personal and/or family history of atopic diseases. Several criteria have been proposed for the diagnosis of AD. Although the clinical features of childhood AD have been widely studied, there has been less large-scale study on adult/adolescent AD. The aim of this study was to investigate the clinical features of adult/adolescent patients with chronic symmetrical eczema/AD and to propose Chinese diagnostic criteria for adult/adolescent AD. Methods: A hospital-based study was performed. Forty-two dermatological centers participated in this study. Adult and adolescent patients (12 years and over) with chronic symmetrical eczema or AD were included in this study. Questionnaires were completed by both patients and investigators. The valid questionnaires were analyzed using EpiData 3.1 and SPSS 17.0 software. Results: A total of 2662 valid questionnaires were collected (1369 male and 1293 female). Of all 2662 patients, 2062 (77.5%) patients had the disease after 12 years old, while only 600 (22.5%) patients had the disease before 12 years old, suggesting late-onset eczema/AD is common. Two thousand one hundred and thirty-nine (80.4%) patients had the disease for more than 6 months. One thousand one hundred and forty-four (43.0%) patients had a personal and/or family history of atopic diseases. One thousand five hundred and forty-eight (58.2%) patients had an elevated total serum IgE and/or eosinophilia and/or positive allergen-specific IgE. Based on these clinical and laboratory features, we proposed Chinese criteria for adult/adolescent AD. Of all 2662 patients, 60.3% were satisfied with our criteria, while only 48.2% satisfied with Hanifin Rajka criteria and 32.7% satisfied with Williams criteria, suggesting a good sensitivity of our criteria in adult/adolescent AD patients. Conclusion: Late-onset of eczema or AD is

  8. Clinical features and molecular characteristics of invasive community-acquired methicillin-resistant Staphylococcus aureus infections in Taiwanese children.

    PubMed

    Chen, Chih-Jung; Su, Lin-Hui; Chiu, Cheng-Hsun; Lin, Tzou-Yien; Wong, Kin-Sun; Chen, Yi-Ywan M; Huang, Yhu-Chering

    2007-11-01

    Highly virulent community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) has been associated with morbidity and mortality in various countries of the world. We characterized the clinical and molecular features of pediatric invasive CA-MRSA infections in Taiwan. Between July 2000 and June 2005, 31 previously healthy children with invasive CA-MRSA infections were identified from 423 children with community-onset methicillin-resistant S. aureus infections. The medical records were reviewed. The clinical isolates, if available, were collected for molecular characterization. Sixteen (51.6%) patients were male, and the mean age was 5.7 years. Adolescents accounted for 9 (29%) cases. Eighteen children had bone and/or joint infections, 14 had deep-seated soft tissue infections, 11 had pneumonia, and 2 had central nervous system infections. Multiorgan involvement was identified in 8 of 20 bacteremic cases. Twenty-two patients (71%) required surgical interventions. The mean hospital stay was 27.4 days. All of the 15 available isolates were classified as sequence type (ST) 59 or its single locus variant and belonged to 2 previously reported community-associated clones containing staphylococcal cassette chromosome mec (SCCmec) type IV or type V(T) in Taiwan. Most of the isolates were multiresistant to clindamycin (94%) and erythromycin (97%). Eleven (73.3%) isolates carried pvl genes, and the strains harboring pvl genes were significantly associated with lung involvement. In conclusion, invasive CA-MRSA infections in pediatric population were not limited to young children. Surgical interventions were often required, and a prolonged course of antibiotic therapy was needed. A multiresistant CA-MRSA clone characterized as ST59 was identified from these children in Taiwan. PMID:17662565

  9. Clinical Features for Mild Hand, Foot and Mouth Disease in China

    PubMed Central

    Liu, Baoyan; Luo, Lin; Yan, Shiyan; Wen, Tiancai; Bai, Wenjing; Li, Hongjiao; Zhang, Guoliang; Lu, Xiaoying; Liu, Yan; He, Liyun

    2015-01-01

    Background Mild hand, foot and mouth disease (HFMD) is at a critical stage owing to its ease of communicability and a higher risk of developing severe complications and death. Clinical diagnosis of mild HFMD was made by the presenting symptoms and signs (symptoms in brief) alone. We aim to evaluate the frequencies of symptoms in a retrospective case series study. Methods We collected epidemiological, demographic, clinical, and laboratory data from outpatient and inpatient settings on the clinical data warehouse system. We principally described the frequencies of symptoms of mild HFMD. Correlations between symptoms with laboratory-confirmed cases were then analyzed. Results The clinical data warehouse system included 3649 probable cases, between 2010 and 2012, of which 956 (26.20%) were laboratory confirmed. The peak incidence was identified in children 2 years of age. A total of 370 of the 956 laboratory confirmed cases (38.70%) were associated with enterovirus 71 (EV71). Logistic regression analysis adjusted for geographical variables, age, sex, month of onset, and time from onset to diagnosis showed that the clinical features constipation (P<0.0001; adjusted OR, 95%CI (2.99, 2.28–3.91)), and blisters (P<0.0001; adjusted OR, 95%CI (2.16, 1.82–2.56)) were positively correlated with the confirmed cases. Conclusions This is the largest case series study, including all the guideline-mentioned symptoms of mild HFMD. Our findings suggest that blisters and constipation should be considered as potential warning signs while front-line clinicians manage surges of children diagnosed with mild HFMD during a pandemic. PMID:26302092

  10. Heterogeneity of clinical features and corresponding antibodies in seven patients with anti-NMDA receptor encephalitis

    PubMed Central

    SÜHS, KURT-WOLFRAM; WEGNER, FLORIAN; SKRIPULETZ, THOMAS; TREBST, CORINNA; TAYEB, SAID BEN; RAAB, PETER; STANGEL, MARTIN

    2015-01-01

    Anti-N-methyl D-aspartate (NMDA) receptor encephalitis is the most common type of encephalitis in the spectrum of autoimmune encephalitis defined by antibodies targeting neuronal surface antigens. In the present study, the clinical spectrum of this disease is presented using instructive cases in correlation with the anti-NMDA receptor antibody titers in the cerebrospinal fluid (CSF) and serum. A total of 7 female patients admitted to the hospital of Hannover Medical School (Hannover, Germany) between 2008 and 2014 were diagnosed with anti-NMDA receptor encephalitis. Among these patients, 3 cases were selected to illustrate the range of similar and distinct clinical features across the spectrum of the disease and to compare anti-NMDA antibody levels throughout the disease course. All patients received immunosuppressive treatment with methylprednisolone, intravenous immunoglobulin and/or plasmapheresis, followed in the majority of patients by second-line therapy with rituximab and cyclophosphamide. The disease course correlated with NMDA receptor antibody titers, and to a greater extent with the ratio between antibody titer and protein concentration. A favorable clinical outcome with a modified Rankin Scale (mRS) score of ≤1 was achieved in 4 patients, 1 patient had an mRS score of 2 after 3 months of observation only, whereas 2 patients remained severely impaired (mRS score 4). Early and aggressive immunosuppressive treatment appears to support a good clinical outcome; however, the clinical signs and symptoms differ distinctively and treatment decisions have to be made on an individual basis. PMID:26622479

  11. Combined central and peripheral demyelination: Clinical features, diagnostic findings, and treatment.

    PubMed

    Cortese, A; Franciotta, D; Alfonsi, E; Visigalli, N; Zardini, E; Diamanti, L; Prunetti, P; Osera, C; Gastaldi, M; Berzero, G; Pichiecchio, A; Piccolo, G; Lozza, A; Piscosquito, G; Salsano, E; Ceroni, M; Moglia, A; Bono, G; Pareyson, D; Marchioni, E

    2016-04-15

    Combined central and peripheral demyelination (CCPD) is rare, and current knowledge is based on case reports and small case series. The aim of our study was to describe the clinical features, diagnostic results, treatment and outcomes in a large cohort of patients with CCPD. Thirty-one patients entered this retrospective, observational, two-center study. In 20 patients (65%) CCPD presented, after an infection, as myeloradiculoneuropathy, encephalopathy, cranial neuropathy, length-dependent peripheral neuropathy, or pseudo-Guillain-Barré syndrome. Demyelinating features of peripheral nerve damage fulfilling European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) electrodiagnostic criteria for CIDP were found in 23 patients (74%), and spatial dissemination of demyelinating lesions on brain MRI fulfilling the 2010 McDonald criteria for multiple sclerosis (MS) in 11 (46%). Two thirds of the patients had a relapsing or progressive disease course, usually related to the appearance of new spinal cord lesions or worsening of the peripheral neuropathy, and showed unsatisfactory responses to high-dose corticosteroids and intravenous immunoglobulins. The clinical presentation of CCPD was severe in 22 patients (71%), who were left significantly disabled. Our data suggest that CCPD has heterogeneous features and shows frequent post-infectious onset, primary peripheral nervous system or central nervous system involvement, a monophasic or chronic disease course, inadequate response to treatments, and a generally poor outcome. We therefore conclude that the current diagnostic criteria for MS and CIDP may not fully encompass the spectrum of possible manifestations of CCPD, whose pathogenesis remains largely unknown. PMID:27000248

  12. Comparing patients with Apert and Crouzon syndromes--clinical features and cranio-maxillofacial surgical reconstruction.

    PubMed

    Stavropoulos, Dimitrios; Tarnow, Peter; Mohlin, Bengt; Kahnberg, Karl-Erik; Hagberg, Catharina

    2012-01-01

    Cranio-maxillofacial malformations, as seen in Crouzon and Apert syndromes, may impose an immense distress on both function and aesthetics of the person affected. The aims of this study were to describe and compare the main facial and intraoral features of patients with Apert and Crouzon syndromes, the clinical manifestations that may be present, additionally to the main syndromic traits, as well as the cranio-maxillofacial surgical treatment protocols followed.Twenty-three patients with Apert syndrome (6 males, 17 females), and 28 patients with Crouzon syndrome (20 males, 8 females) were evaluated for general medical aspects, craniofacial characteristics, dentoalveolar traits before and after the final orthognathic surgery, and types and timing of cranio-maxillofacial operations. Mental retardation, associated additional malformations, cleft palate, and extensive lateral palatal soft tissue swellings were more common in children with Apert syndrome. In both syndromes, clinical findings included concave profile, negative overjet, posterior crossbites, anterior openbite, and dental midline deviation, which were corrected in almost all cases with the final orthognathic surgery, with the exception of the lateral crossbites, including more than one tooth pair, which were persisting in about half of the cases. Cranial vault decompression and/or reshaping, midfacial and orbital advancement procedures, often in conjunction with a mandibular setback, were the most frequent cranio-maxillofacial operations performed. In conclusion, Apert syndrome is more asymmetric in nature and a more severe clinical entity than Crouzon syndrome. The syndromic dentofacial features of both conditions could be significantly improved after a series of surgical procedures in almost all cases with the exception of the posterior crossbites, with haIf of them persisting post-surgically. PMID:22611902

  13. Demographic, clinical, and laboratory features of Turkish patients with late onset ankylosing spondylitis

    PubMed Central

    Karaarslan, Ahmet; Yilmaz, Hatice; Aycan, Hakan; Orman, Mehmet; Kobak, Senol

    2015-01-01

    Ankylosing spondylitis (AS) is a chronic inflammatory disease, which typically begins in early decades of life with primarily axial joints involvement. This disease rarely affects patients older than 50 years of age. The aim of this study was to compare and evaluate the demographic, clinical, and laboratory features of late onset and early onset AS patients who were followed up in a single rheumatology center. A total of 339 patients who have been diagnosed with AS according to modified New York criteria were included in the study. The patients whose initial symptoms were observed after 50 years of age were accepted as late onset AS. Out of 339 patients, 27 (7.9%) were diagnosed as late onset AS and 312 (92.3%) patients were evaluated as early onset AS. Of 27 late onset patients, 10 were male and 17 were female. Delay in the diagnosis was 5.8 years for early onset AS, while it was 3.8 years for late onset AS (p = 0.001). Higher levels of acute phase reactants and more methotrexate (MTX) use were detected in early onset AS patients compared to late onset AS (p = 0.001, p = 0.007, respectively). Statistically, there was no difference between these two groups, with regard to disease clinical activity indexes, anthropometric measurement parameters, uveitis and peripheral joint involvement. In this study, we showed that early and late onset AS patients may present with different clinical, genetic, and laboratory features. Late onset AS patients are characterized with lower human leukocyte antigen-B27 sequence, less inflammatory sign, delayed diagnosis, and less MTX and anti-tumor necrosis factor alpha drug usage. PMID:26295296

  14. Demographic, clinical, and laboratory features of Turkish patients with late onset ankylosing spondylitis.

    PubMed

    Karaarslan, Ahmet; Yilmaz, Hatice; Aycan, Hakan; Orman, Mehmet; Kobak, Senol

    2015-01-01

    Ankylosing spondylitis (AS) is a chronic inflammatory disease, which typically begins in early decades of life with primarily axial joints involvement. This disease rarely affects patients older than 50 years of age. The aim of this study was to compare and evaluate the demographic, clinical, and laboratory features of late onset and early onset AS patients who were followed up in a single rheumatology center. A total of 339 patients who have been diagnosed with AS according to modified New York criteria were included in the study. The patients whose initial symptoms were observed after 50 years of age were accepted as late onset AS. Out of 339 patients, 27 (7.9%) were diagnosed as late onset AS and 312 (92.3%) patients were evaluated as early onset AS. Of 27 late onset patients, 10 were male and 17 were female. Delay in the diagnosis was 5.8 years for early onset AS, while it was 3.8 years for late onset AS (p = 0.001). Higher levels of acute phase reactants and more methotrexate (MTX) use were detected in early onset AS patients compared to late onset AS (p = 0.001, p = 0.007, respectively). Statistically, there was no difference between these two groups, with regard to disease clinical activity indexes, anthropometric measurement parameters, uveitis and peripheral joint involvement. In this study, we showed that early and late onset AS patients may present with different clinical, genetic, and laboratory features. Late onset AS patients are characterized with lower human leukocyte antigen-B27 sequence, less inflammatory sign, delayed diagnosis, and less MTX and anti-tumor necrosis factor alpha drug usage. PMID:26295296

  15. Amebiasis in HIV-1-infected Japanese men: clinical features and response to therapy.

    PubMed

    Watanabe, Koji; Gatanaga, Hiroyuki; Escueta-de Cadiz, Aleyla; Tanuma, Junko; Nozaki, Tomoyoshi; Oka, Shinichi

    2011-09-01

    Invasive amebic diseases caused by Entamoeba histolytica are increasing among men who have sex with men and co-infection of ameba and HIV-1 is an emerging problem in developed East Asian countries. To characterize the clinical and epidemiological features of invasive amebiasis in HIV-1 patients, the medical records of 170 co-infected cases were analyzed retrospectively, and E. histolytica genotype was assayed in 14 cases. In this series of HIV-1-infected patients, clinical presentation of invasive amebiasis was similar to that described in the normal host. High fever, leukocytosis and high CRP were associated with extraluminal amebic diseases. Two cases died from amebic colitis (resulting in intestinal perforation in one and gastrointestinal bleeding in one), and three cases died from causes unrelated to amebiasis. Treatment with metronidazole or tinidazole was successful in the other 165 cases. Luminal treatment was provided to 83 patients following metronidazole or tinidazole treatment. However, amebiasis recurred in 6 of these, a frequency similar to that seen in patients who did not receive luminal treatment. Recurrence was more frequent in HCV-antibody positive individuals and those who acquired syphilis during the follow-up period. Various genotypes of E. histolytica were identified in 14 patients but there was no correlation between genotype and clinical features. The outcome of metronidazole and tinidazole treatment of uncomplicated amebiasis was excellent even in HIV-1-infected individuals. Luminal treatment following metronidazole or tinidazole treatment does not reduce recurrence of amebiasis in high risk populations probably due to amebic re-infection. PMID:21931875

  16. Comparison of Clinical and Ultrasonographic Features of Poorly Differentiated Thyroid Carcinoma and Papillary Thyroid Carcinoma

    PubMed Central

    Zhang, Bo; Niu, Hui-Min; Wu, Qiong; Zhou, Jiong; Jiang, Yu-Xin; Yang, Xiao; Li, Jian-Chu; Zhao, Rui-Na; Wang, Ming; Li, Kang-Ning; Zhu, Shen-Ling; Xia, Yu; Zhong, Ding-Rong

    2016-01-01

    Background: The clinical behavior and management of poorly differentiated thyroid carcinoma (PDTC) are very different from papillary thyroid carcinoma (PTC). By comparing the clinical and ultrasonographic features between the two tumors, we proposed to provide more possibilities for recognizing PDTC before treatment. Methods: The data of 13 PDTCs and 39 age- and gender-matched PTCs in Peking Union Medical College Hospital between December 2003 and September 2013 were retrospectively reviewed. The clinical and ultrasonic features between the two groups were compared. Results: The frequencies of family history of carcinoma, complication with other thyroid lesions, lymph node metastases, recurrent laryngeal nerve injuries, and distant metastases were higher in PDTCs (30.8%, 61.6%, 69.2%, 23.1%, and 46.2%, respectively) than those in PTCs (2.6%, 23.1%, 25.6%, 2.6%, and 2.6%, respectively) (P < 0.05). The mortality rate of PDTCs was greatly higher than PTCs (P < 0.01). Conventional ultrasound showed that the size of PDTCs was larger than that of PTCs (3.1 ± 1.9 cm vs. 1.7 ± 1.0 cm). Clear margins and rich and/or irregular blood flow were found in 92.3% of PDTCs, which differed substantially from PTCs (51.7% and 53.8%, respectively) (P < 0.05). Conclusions: PDTC is more aggressive and its mortality rate is higher than PTCs. Accordingly, more attention should be given to suspicious thyroid cancer nodules that show large size, regular shape, and rich blood flow signals on ultrasound to exclude the possibility of PDTCs. PMID:26830987

  17. Gambling disorder in financial markets: Clinical and treatment-related features

    PubMed Central

    Shin, Young-Chul; Choi, Sam-Wook; Ha, Juwon; Choi, Jung-Seok; Kim, Dai-Jin

    2015-01-01

    Background and Aims To date, few studies have examined the clinical manifestation of disordered gamblers in financial markets. This study examined the differences in the clinical and treatment-related features of gambling disorder between financial markets and horse races. Methods Subjects who met the DSM-IV criteria for pathological gambling (PG) and who sought treatment were assessed by retrospective chart review. One hundred forty-four subjects were included in this sample, which consisted of the following groups: financial markets (n = 45; 28.6%) and horse races (n = 99; 71.4%). Results Multiple similar manifestations were found between the groups, including severity of PG, age of PG onset, amounts of gambling debts, drinking days per week, depressive mood, duration of seeking treatment after the onset of PG, and treatment follow-up duration. However, disordered gamblers who invested in the financial market were significantly more likely to be educated (p = 0.003), live with their spouses (p = 0.007), have full-time jobs (p = 0.006), and they were more likely to participate in the first type of gambling than the horse races group (p<0.001). Furthermore, the financial markets group received the anti-craving medication less often than the horse races group (p = 0.04). Discussion and Conclusions: These findings suggest that disordered gamblers in financial markets show different socio-demographic, clinical and treatment-related features compared with the horse race gamblers, despite a similar severity of gambling disorder. Understanding these differential manifestations may provide insight into prevention and treatment development for specific types of gambling. PMID:26690619

  18. Overlap of clinical features of Smith-Magenis & Down Syndrome in newborns and infants