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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

    2016-01-01

    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

  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

    2016-08-01

    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

  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. 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

  17. [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

  18. 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

  19. 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

  20. 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

  1. 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

  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. 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

  5. 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…

  6. 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

  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

    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 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

  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. 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

  19. 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

  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. [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

  2. 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

  3. 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.

  4. 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

  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. 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

  10. 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

  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. 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

  16. 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

  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. [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

  2. 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

  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. 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

  18. 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

  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. 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

  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. 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

  4. 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

  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. 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

  7. 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

  8. 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

  9. 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

  10. 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

  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. 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

  13. 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

  14. 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

  15. 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

  16. 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

  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. 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

  1. 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

  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. 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

  5. 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

  6. 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

  7. 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

  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. 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

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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

  18. 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

  19. 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

  20. 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

  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. 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

  16. [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

  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. 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

  20. 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

  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. 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

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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

  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 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

  1. 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

  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. 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

  7. 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

  8. 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

  9. 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

  10. 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

  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. 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

  13. 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

  14. 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

  15. 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

  16. [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

  17. 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

  18. 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

  19. 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

  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. 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

  7. 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

  8. 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

  9. 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

  10. 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