Next-Generation Sequencing for Infectious Disease Diagnosis and Management: A Report of the Association for Molecular Pathology.

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Lefterova, Martina I; Suarez, Carlos J; Banaei, Niaz; Pinsky, Benjamin A

2015-11-01

Next-generation sequencing (NGS) technologies are increasingly being used for diagnosis and monitoring of infectious diseases. Herein, we review the application of NGS in clinical microbiology, focusing on genotypic resistance testing, direct detection of unknown disease-associated pathogens in clinical specimens, investigation of microbial population diversity in the human host, and strain typing. We have organized the review into three main sections: i) applications in clinical virology, ii) applications in clinical bacteriology, mycobacteriology, and mycology, and iii) validation, quality control, and maintenance of proficiency. Although NGS holds enormous promise for clinical infectious disease testing, many challenges remain, including automation, standardizing technical protocols and bioinformatics pipelines, improving reference databases, establishing proficiency testing and quality control measures, and reducing cost and turnaround time, all of which would be necessary for widespread adoption of NGS in clinical microbiology laboratories. Copyright © 2015 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

Clinical Whole-Exome Sequencing for the Diagnosis of Mendelian Disorders

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Yang, Yaping; Muzny, Donna M.; Reid, Jeffrey G.; Bainbridge, Matthew N.; Willis, Alecia; Ward, Patricia A.; Braxton, Alicia; Beuten, Joke; Xia, Fan; Niu, Zhiyv; Hardison, Matthew; Person, Richard; Bekheirnia, Mir Reza; Leduc, Magalie S.; Kirby, Amelia; Pham, Peter; Scull, Jennifer; Wang, Min; Ding, Yan; Plon, Sharon E.; Lupski, James R.; Beaudet, Arthur L.; Gibbs, Richard A.; Eng, Christine M.

2014-01-01

BACKGROUND Whole-exome sequencing is a diagnostic approach for the identification of molecular defects in patients with suspected genetic disorders. METHODS We developed technical, bioinformatic, interpretive, and validation pipelines for whole-exome sequencing in a certified clinical laboratory to identify sequence variants underlying disease phenotypes in patients. RESULTS We present data on the first 250 probands for whom referring physicians ordered whole-exome sequencing. Patients presented with a range of phenotypes suggesting potential genetic causes. Approximately 80% were children with neurologic pheno-types. Insurance coverage was similar to that for established genetic tests. We identified 86 mutated alleles that were highly likely to be causative in 62 of the 250 patients, achieving a 25% molecular diagnostic rate (95% confidence interval, 20 to 31). Among the 62 patients, 33 had autosomal dominant disease, 16 had auto-somal recessive disease, and 9 had X-linked disease. A total of 4 probands received two nonoverlapping molecular diagnoses, which potentially challenged the clinical diagnosis that had been made on the basis of history and physical examination. A total of 83% of the autosomal dominant mutant alleles and 40% of the X-linked mutant alleles occurred de novo. Recurrent clinical phenotypes occurred in patients with mutations that were highly likely to be causative in the same genes and in different genes responsible for genetically heterogeneous disorders. CONCLUSIONS Whole-exome sequencing identified the underlying genetic defect in 25% of consecutive patients referred for evaluation of a possible genetic condition. (Funded by the National Human Genome Research Institute.) PMID:24088041

Early diagnosis of Werner’s syndrome using exome-wide sequencing in a single, atypical patient

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Eleanor eRaffan

2011-03-01

Full Text Available Genetic diagnosis of inherited metabolic disease is conventionally achieved through syndrome recognition and targeted gene sequencing, but many patients receive no specific diagnosis. Next generation sequencing allied to capture of expressed sequences from genomic DNA now offers a powerful new diagnostic approach. Barriers to routine diagnostic use include cost, and the complexity of interpreting results arising from simultaneous identification of large numbers of variants. We applied exome-wide sequencing to an individual, 16 year old daughter of consanguineous parents with a novel syndrome of short stature, severe insulin resistance, ptosis and microcephaly. Pulldown of expressed sequences from genomic DNA followed by massively parallel sequencing was undertaken. Single nucleotide variants (SNVs were called using SAMtools prior to filtering based on sequence quality and existence in control genomes and exomes. Of 485 genetic variants predicted to alter protein sequence and absent from control data, 24 were homozygous in the patient. One mutation – the p.Arg732X mutation in the WRN gene – has previously been reported in Werner’s syndrome (WS. On re-evaluation of the patient several early features of WS were detected including loss of fat from the extremities and frontal hair thinning. Lymphoblastoid cells from the proband exhibited a defective decatenation checkpoint, consistent with loss of WRN activity. We have thus diagnosed WS some 15 years earlier than average, permitting aggressive prophylactic therapy and screening for WS complications, illustrating the potential of exome-wide sequencing to achieve early diagnosis and change management of rare autosomal recessive disease, even in individual patients of consanguineous parentage with apparently novel syndromes.

Impact of exome sequencing in inflammatory bowel disease

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Cardinale, Christopher J; Kelsen, Judith R; Baldassano, Robert N; Hakonarson, Hakon

2013-01-01

Approaches to understanding the genetic contribution to inflammatory bowel disease (IBD) have continuously evolved from family- and population-based epidemiology, to linkage analysis, and most recently, to genome-wide association studies (GWAS). The next stage in this evolution seems to be the sequencing of the exome, that is, the regions of the human genome which encode proteins. The GWAS approach has been very fruitful in identifying at least 163 loci as being associated with IBD, and now, exome sequencing promises to take our genetic understanding to the next level. In this review we will discuss the possible contributions that can be made by an exome sequencing approach both at the individual patient level to aid with disease diagnosis and future therapies, as well as in advancing knowledge of the pathogenesis of IBD. PMID:24187447

[Diagnosis of mitochondrial disorders in children with next generation sequencing].

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Liu, Zhimei; Fang, Fang; Ding, Changhong; Zhang, Weihua; Li, Jiuwei; Yang, Xinying; Wang, Xiaohui; Wu, Yun; Wang, Hongmei; Liu, Liying; Han, Tongli; Wang, Xu; Chen, Chunhong; Lyu, Junlan; Wu, Husheng

2015-10-01

To explore the application value of next generation sequencing (NGS) in the diagnosis of mitochondrial disorders. According to mitochondrial disease criteria, genomic DNA was extracted using standard procedure from peripheral venous blood of patients with suspected mitochondrial disease collected from neurological department of Beijing Children's Hospital Affiliated to Capital Medical University between October 2012 and February 2014. Targeted NGS to capture and sequence the entire mtDNA and exons of the 1 000 nuclear genes related to mitochondrial structure and function. Clinical data were collected from patients diagnosed at a molecular level, then clinical features and the relationship between genotype and phenotype were analyzed. Mutation was detected in 21 of 70 patients with suspected mitochondrial disease, in whom 10 harbored mtDNA mutation, while 11 nuclear DNA (nDNA) mutation. In 21 patients, 1 was diagnosed congenital myasthenic syndrome with episodic apnea due to CHAT gene p.I187T homozygous mutation, and 20 were diagnosed mitochondrial disease, in which 10 were Leigh syndrome, 4 were mitochondrial encephalomyopathy with lactic acidosis and stroke like episodes syndrome, 3 were Leber hereditary optic neuropathy (LHON) and LHON plus, 2 were mitochondrial DNA depletion syndrome and 1 was unknown. All the mtDNA mutations were point mutations, which contained A3243G, G3460A, G11778A, T14484C, T14502C and T14487C. Ten mitochondrial disease patients harbored homozygous or compound heterozygous mutations in 5 genes previously shown to cause disease: SURF1, PDHA1, NDUFV1, SUCLA2 and SUCLG1, which had 14 mutations, and 7 of the 14 mutations have not been reported. NGS has a certain application value in the diagnosis of mitochondrial diseases, especially in Leigh syndrome atypical mitochondrial syndrome and rare mitochondrial disorders.

Differential diagnosis of rheumatic diseases

International Nuclear Information System (INIS)

Lingg, G.; Schorn, C.

2006-01-01

Which imaging modalities are appropriate for the Differential diagnosis of Rheumatic diseases. MRI has far most the highest sensitivity and is unequaled in its brilliant presentation of Anatomy and Pathology. But it is sometimes forgotten, that this is at least in part the result of carefully selected sequences, dedicated to the expected result. In a method totally independent of any result, this should not be the case. In contrary this method should be highly standardised and regardless what will be the findings. This is true for Plain X-ray. It will be shown, that already the outer silhouette of the soft parts with different features of swelling, and differences in density and even more - defects or appositions of the bony silhouette in the majority of cases at least will allow to classify the patient for a group of diseases and in many cases will lead to a definite diagnosis. Differential diagnoses like Rheumatoid Arthritis versus Psoriatic Arthritis or simply but not always simple - inflammatory Arthritis versus degenerative disease - are allowed to be answered definitely, not always so in MRI. The condition of the subchondral bone can give hints, how advanced and how active the disease is at present. Plain X-ray offers high specifity in the differential diagnoses of Rheumatic diseases, it is well standardised and it is a device, to use independent from any suspected findings. So it is the method of choice for questions of differential diagnosis. This is even more true, thinking of the possibility, to investigate all clinically involved regions with not to much extended efforts, whereas MRI and CT are used normally for only one region. (orig.) [de

Partial status epilepticus - rapid genetic diagnosis of Alpers' disease.

LENUS (Irish Health Repository)

McCoy, Bláthnaid

2011-11-01

We describe four children with a devastating encephalopathy characterised by refractory focal seizures and variable liver dysfunction. We describe their electroencephalographic, radiologic, genetic and pathologic findings. The correct diagnosis was established by rapid gene sequencing. POLG1 based Alpers\\' disease should be considered in any child presenting with partial status epilepticus.

Retinal Diseases Caused by Mutations in Genes Not Specifically Associated with the Clinical Diagnosis.

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Xia Wang

Full Text Available When seeking a confirmed molecular diagnosis in the research setting, patients with one descriptive diagnosis of retinal disease could carry pathogenic variants in genes not specifically associated with that description. However, this event has not been evaluated systematically in clinical diagnostic laboratories that validate fully all target genes to minimize false negatives/positives.We performed targeted next-generation sequencing analysis on 207 ocular disease-related genes for 42 patients whose DNA had been tested negative for disease-specific panels of genes known to be associated with retinitis pigmentosa, Leber congenital amaurosis, or exudative vitreoretinopathy.Pathogenic variants, including single nucleotide variations and copy number variations, were identified in 9 patients, including 6 with variants in syndromic retinal disease genes and 3 whose molecular diagnosis could not be distinguished easily from their submitted clinical diagnosis, accounting for 21% (9/42 of the unsolved cases.Our study underscores the clinical and genetic heterogeneity of retinal disorders and provides valuable reference to estimate the fraction of clinical samples whose retinal disorders could be explained by genes not specifically associated with the corresponding clinical diagnosis. Our data suggest that sequencing a larger set of retinal disorder related genes can increase the molecular diagnostic yield, especially for clinically hard-to-distinguish cases.

Use of Targeted Exome Sequencing for Molecular Diagnosis of Skeletal Disorders

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Polla, Daniel L.; Cardoso, Maria T. O.; Silva, Mayara C. B.; Cardoso, Isabela C. C.; Medina, Cristina T. N.; Araujo, Rosenelle; Fernandes, Camila C.; Reis, Alessandra M. M.; de Andrade, Rosangela V.; Pereira, Rinaldo W.; Pogue, Robert

2015-01-01

Genetic disorders of the skeleton comprise a large group of more than 450 clinically distinct and genetically heterogeneous diseases associated with mutations in more than 300 genes. Achieving a definitive diagnosis is complicated due to the genetic heterogeneity of these disorders, their individual rarity and their diverse radiographic presentations. We used targeted exome sequencing and designed a 1.4Mb panel for simultaneous testing of more than 4,800 exons in 309 genes involved in skeletal disorders. DNA from 69 individuals from 66 families with a known or suspected clinical diagnosis of a skeletal disorder was analyzed. Of 36 cases with a specific clinical hypothesis with a known genetic basis, mutations were identified for eight cases (22%). Of 20 cases with a suspected skeletal disorder but without a specific diagnosis, four causative mutations were identified. Also included were 11 cases with a specific skeletal disorder but for which there was at the time no known associated gene. For these cases, one mutation was identified in a known skeletal disease genes, and re-evaluation of the clinical phenotype in this case changed the diagnoses from osteodysplasia syndrome to Apert syndrome. These results suggest that the NGS panel provides a fast, accurate and cost-effective molecular diagnostic tool for identifying mutations in a highly genetically heterogeneous set of disorders such as genetic skeletal disorders. The data also stress the importance of a thorough clinical evaluation before DNA sequencing. The strategy should be applicable to other groups of disorders in which the molecular basis is largely known. PMID:26380986

Exome sequencing is an efficient tool for variant late-infantile neuronal ceroid lipofuscinosis molecular diagnosis.

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Liliana Catherine Patiño

Full Text Available The neuronal ceroid-lipofuscinoses (NCL is a group of neurodegenerative disorders characterized by epilepsy, visual failure, progressive mental and motor deterioration, myoclonus, dementia and reduced life expectancy. Classically, NCL-affected individuals have been classified into six categories, which have been mainly defined regarding the clinical onset of symptoms. However, some patients cannot be easily included in a specific group because of significant variation in the age of onset and disease progression. Molecular genetics has emerged in recent years as a useful tool for enhancing NCL subtype classification. Fourteen NCL genetic forms (CLN1 to CLN14 have been described to date. The variant late-infantile form of the disease has been linked to CLN5, CLN6, CLN7 (MFSD8 and CLN8 mutations. Despite advances in the diagnosis of neurodegenerative disorders mutations in these genes may cause similar phenotypes, which rends difficult accurate candidate gene selection for direct sequencing. Three siblings who were affected by variant late-infantile NCL are reported in the present study. We used whole-exome sequencing, direct sequencing and in silico approaches to identify the molecular basis of the disease. We identified the novel c.1219T>C (p.Trp407Arg and c.1361T>C (p.Met454Thr MFSD8 pathogenic mutations. Our results highlighted next generation sequencing as a novel and powerful methodological approach for the rapid determination of the molecular diagnosis of NCL. They also provide information regarding the phenotypic and molecular spectrum of CLN7 disease.

"Transcriptomics": molecular diagnosis of inborn errors of metabolism via RNA-sequencing.

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Kremer, Laura S; Wortmann, Saskia B; Prokisch, Holger

2018-01-25

Exome wide sequencing techniques have revolutionized molecular diagnostics in patients with suspected inborn errors of metabolism or neuromuscular disorders. However, the diagnostic yield of 25-60% still leaves a large fraction of individuals without a diagnosis. This indicates a causative role for non-exonic regulatory variants not covered by whole exome sequencing. Here we review how systematic RNA-sequencing analysis (RNA-seq, "transcriptomics") lead to a molecular diagnosis in 10-35% of patients in whom whole exome sequencing failed to do so. Importantly, RNA-sequencing based discoveries cannot only guide molecular diagnosis but might also unravel therapeutic intervention points such as antisense oligonucleotide treatment for splicing defects as recently reported for spinal muscular atrophy.

Norrie disease: first mutation report and prenatal diagnosis in an Indian family.

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Ghosh, Manju; Sharma, Shipra; Shastri, Shivaram; Arora, Sadhna; Shukla, Rashmi; Gupta, Neerja; Deka, Deepika; Kabra, Madhulika

2012-11-01

Norrie Disease (ND) is a rare X-linked recessive disorder characterised by congenital blindness due to severe retinal dysgenesis. Hearing loss and intellectual disability is present in 30-50 % cases. ND is caused by mutations in the NDP gene, located at Xp11.3. The authors describe mutation analysis of a proband with ND and subsequently prenatal diagnosis. Sequence analysis of the NDP gene revealed a hemizygous missense mutation arginine to serine in codon 41 (p.Arg41Ser) in the affected child. Mother was carrier for the mutation. In a subsequent di-chorionic di-amniotic pregnancy, the authors performed prenatal diagnosis by mutation analysis on chorionic villi sample at 11 wk of gestation. The fetuses were unaffected. This is a first mutation report and prenatal diagnosis of a familial case of Norrie disease from India. The importance of genetic testing of Norrie disease for confirmation, carrier testing, prenatal diagnosis and genetic counseling is emphasized.

Diagnosis of Pompe disease

DEFF Research Database (Denmark)

Vissing, John; Lukacs, Zoltan; Straub, Volker

2013-01-01

The diagnosis of Pompe disease (acid maltase deficiency, glycogen storage disease type II) in children and adults can be challenging because of the heterogeneous clinical presentation and considerable overlap of signs and symptoms found in other neuromuscular diseases. This review evaluates some...... to identify late-onset Pompe disease often leads to false-negative results and subsequent delays in identification and treatment of the disorder. Serum creatine kinase level can be normal or only mildly elevated in late-onset Pompe disease and is not very helpful alone to suggest the diagnosis...

A Baseline Algorithm for Molecular Diagnosis of Genetic Eye Diseases: Ophthalmologist’s Perspective

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Hande Taylan Şekeroğlu

2016-12-01

Full Text Available To the Editor: Genetic eye diseases constitute a large and heterogeneous group. Individual diseases may cause multiple structural/functional anomalies and developmental features. Family history may be suggestive; however, it may also be challenging, particularly in late-onset conditions or in cases of variable expression. In the current era of genetic advances, diagnosis of a genetic eye disease is facilitated by well-established collaboration between ophthalmologists and geneticists, as increasingly more patients will be asking for genetic counseling and prenatal diagnosis in addition to ophthalmologic management. Molecular investigation of a genetic eye disease requires customized analysis and advanced technology in addition to the requisite detailed family history and accurate ophthalmological diagnosis. A common indication for genetic testing is the validation of a preliminary diagnosis made in clinical practice. The need to determine the prognostic implications of the genotype, assessment of the recurrence risk and in particular, the possibility of specific gene therapy in the near future encourages clinicians to pursue genetic research. We present here a baseline algorithm covering common genetic mechanisms in order to outline a basic molecular approach for ophthalmologists. The first step of the flow chart, a prudent clinical examination with complete description of the phenotype, is indispensible for making a precise and accurate preliminary diagnosis (Figure 1. If the phenotype is pathognomonic, Sanger sequencing is preferred for confirmation.1 A previously established genotype-phenotype correlation may add to the value, either by providing accurate prognostic information or by indicating which particular mutation to look for. One such example may be electroretinographic supranormal rod response, indicating KCNV2 mutation type cone dystrophy, which can be precisely detected by Sanger sequencing or qPCR.2 Conventional karyotyping reveals

Human Genome Sequencing in Health and Disease

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Gonzaga-Jauregui, Claudia; Lupski, James R.; Gibbs, Richard A.

2013-01-01

Following the “finished,” euchromatic, haploid human reference genome sequence, the rapid development of novel, faster, and cheaper sequencing technologies is making possible the era of personalized human genomics. Personal diploid human genome sequences have been generated, and each has contributed to our better understanding of variation in the human genome. We have consequently begun to appreciate the vastness of individual genetic variation from single nucleotide to structural variants. Translation of genome-scale variation into medically useful information is, however, in its infancy. This review summarizes the initial steps undertaken in clinical implementation of personal genome information, and describes the application of whole-genome and exome sequencing to identify the cause of genetic diseases and to suggest adjuvant therapies. Better analysis tools and a deeper understanding of the biology of our genome are necessary in order to decipher, interpret, and optimize clinical utility of what the variation in the human genome can teach us. Personal genome sequencing may eventually become an instrument of common medical practice, providing information that assists in the formulation of a differential diagnosis. We outline herein some of the remaining challenges. PMID:22248320

Congenital Heart Disease: Causes, Diagnosis, Symptoms, and Treatments.

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Sun, RongRong; Liu, Min; Lu, Lei; Zheng, Yi; Zhang, Peiying

2015-07-01

The congenital heart disease includes abnormalities in heart structure that occur before birth. Such defects occur in the fetus while it is developing in the uterus during pregnancy. About 500,000 adults have congenital heart disease in USA (WebMD, Congenital heart defects medications, www.WebMD.com/heart-disease/tc/congenital-heart-defects-medications , 2014). 1 in every 100 children has defects in their heart due to genetic or chromosomal abnormalities, such as Down syndrome. The excessive alcohol consumption during pregnancy and use of medications, maternal viral infection, such as Rubella virus, measles (German), in the first trimester of pregnancy, all these are risk factors for congenital heart disease in children, and the risk increases if parent or sibling has a congenital heart defect. These are heart valves defects, atrial and ventricular septa defects, stenosis, the heart muscle abnormalities, and a hole inside wall of the heart which causes defect in blood circulation, heart failure, and eventual death. There are no particular symptoms of congenital heart disease, but shortness of breath and limited ability to do exercise, fatigue, abnormal sound of heart as heart murmur, which is diagnosed by a physician while listening to the heart beats. The echocardiogram or transesophageal echocardiogram, electrocardiogram, chest X-ray, cardiac catheterization, and MRI methods are used to detect congenital heart disease. Several medications are given depending on the severity of this disease, and catheter method and surgery are required for serious cases to repair heart valves or heart transplantation as in endocarditis. For genetic study, first DNA is extracted from blood followed by DNA sequence analysis and any defect in nucleotide sequence of DNA is determined. For congenital heart disease, genes in chromosome 1 show some defects in nucleotide sequence. In this review the causes, diagnosis, symptoms, and treatments of congenital heart disease are described.

Whole-exome sequencing identified a variant in EFTUD2 gene in establishing a genetic diagnosis.

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Rengasamy Venugopalan, S; Farrow, E G; Lypka, M

2017-06-01

Craniofacial anomalies are complex and have an overlapping phenotype. Mandibulofacial Dysostosis and Oculo-Auriculo-Vertebral Spectrum are conditions that share common craniofacial phenotype and present a challenge in arriving at a diagnosis. In this report, we present a case of female proband who was given a differential diagnosis of Treacher Collins syndrome or Hemifacial Microsomia without certainty. Prior genetic testing reported negative for 22q deletion and FGFR screenings. The objective of this study was to demonstrate the critical role of whole-exome sequencing in establishing a genetic diagnosis of the proband. The participants were 14½-year-old affected female proband/parent trio. Proband/parent trio were enrolled in the study. Surgical tissue sample from the proband and parental blood samples were collected and prepared for whole-exome sequencing. Illumina HiSeq 2500 instrument was used for sequencing (125 nucleotide reads/84X coverage). Analyses of variants were performed using custom-developed software, RUNES and VIKING. Variant analyses following whole-exome sequencing identified a heterozygous de novo pathogenic variant, c.259C>T (p.Gln87*), in EFTUD2 (NM_004247.3) gene in the proband. Previous studies have reported that the variants in EFTUD2 gene were associated with Mandibulofacial Dysostosis with Microcephaly. Patients with facial asymmetry, micrognathia, choanal atresia and microcephaly should be analyzed for variants in EFTUD2 gene. Next-generation sequencing techniques, such as whole-exome sequencing offer great promise to improve the understanding of etiologies of sporadic genetic diseases. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Diagnosis and pathology of endocrine diseases

International Nuclear Information System (INIS)

Shriver, B.D.

1988-01-01

This book contains 22 papers under the headings of Diagnosis and Pathology of endocrine diseases. Topics covered include: Laboratory tests in the diagnosis and management of thyroid disorders, Pathology of thyroid diseases, Diagnosis of adrenourtical disease, Radiologic techniques in evaluating endocrine disorders; and the Pituitary and adrenal glands

Diagnosis and pathology of endocrine diseases

Energy Technology Data Exchange (ETDEWEB)

Shriver, B.D.

1988-01-01

This book contains 22 papers under the headings of Diagnosis and Pathology of endocrine diseases. Topics covered include: Laboratory tests in the diagnosis and management of thyroid disorders, Pathology of thyroid diseases, Diagnosis of adrenourtical disease, Radiologic techniques in evaluating endocrine disorders; and the Pituitary and adrenal glands.

Celiac Disease Diagnosis and Management

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Leffler, Daniel

2012-01-01

Celiac disease is one of the most prevalent autoimmune gastrointestinal disorders but as the case of Ms. J illustrates, diagnosis is often delayed or missed. Based on serology studies, the prevalence of celiac disease in many populations is estimated to be approximately 1% and has been increasing steadily over the last 50 years. Evaluation for celiac disease is generally straightforward, and uses commonly available serologic tests, however the signs and symptoms of celiac disease are nonspecific and highly heterogeneous making diagnosis difficult. While celiac disease is often considered a mild disorder treatable with simple dietary changes, in reality celiac disease imparts considerable risks including reduced bone mineral density, impaired quality of life, and increased overall mortality. In addition, the gluten free diet is highly burdensome and can profoundly affect patients and their families. For these reasons, care of individuals with celiac disease requires prompt diagnosis and ongoing multidisciplinary management. PMID:21990301

High-Throughput Sequencing, a VersatileWeapon to Support Genome-Based Diagnosis in Infectious Diseases: Applications to Clinical Bacteriology

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Ségolène Caboche

2014-04-01

Full Text Available The recent progresses of high-throughput sequencing (HTS technologies enable easy and cost-reduced access to whole genome sequencing (WGS or re-sequencing. HTS associated with adapted, automatic and fast bioinformatics solutions for sequencing applications promises an accurate and timely identification and characterization of pathogenic agents. Many studies have demonstrated that data obtained from HTS analysis have allowed genome-based diagnosis, which has been consistent with phenotypic observations. These proofs of concept are probably the first steps toward the future of clinical microbiology. From concept to routine use, many parameters need to be considered to promote HTS as a powerful tool to help physicians and clinicians in microbiological investigations. This review highlights the milestones to be completed toward this purpose.

Sanger sequencing as a first-line approach for molecular diagnosis of Andersen-Tawil syndrome [version 1; referees: 2 approved

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Armando Totomoch-Serra

2017-06-01

Full Text Available In 1977, Frederick Sanger developed a new method for DNA sequencing based on the chain termination method, now known as the Sanger sequencing method (SSM.  Recently, massive parallel sequencing, better known as next-generation sequencing (NGS,  is replacing the SSM for detecting mutations in cardiovascular diseases with a genetic background. The present opinion article wants to remark that “targeted” SSM is still effective as a first-line approach for the molecular diagnosis of some specific conditions, as is the case for Andersen-Tawil syndrome (ATS. ATS is described as a rare multisystemic autosomal dominant channelopathy syndrome caused mainly by a heterozygous mutation in the KCNJ2 gene. KCJN2 has particular characteristics that make it attractive for “directed” SSM. KCNJ2 has a sequence of 17,510 base pairs (bp, and a short coding region with two exons (exon 1=166 bp and exon 2=5220 bp, half of the mutations are located in the C-terminal cytosolic domain, a mutational hotspot has been described in residue Arg218, and this gene explains the phenotype in 60% of ATS cases that fulfill all the clinical criteria of the disease. In order to increase the diagnosis of ATS we urge cardiologists to search for facial and muscular abnormalities in subjects with frequent ventricular arrhythmias (especially bigeminy and prominent U waves on the electrocardiogram.

Consensus Conference: A reappraisal of Gaucher disease - diagnosis and disease management algorithms

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Mistry, Pramod K.; Cappellini, Maria Domenica; Lukina, Elena; Özsan, Hayri; Pascual, Sara Mach; Rosenbaum, Hanna; Solano, Maria Helena; Spigelman, Zachary; Villarrubia, Jesús; Watman, Nora Patricia; Massenkeil, Gero

2010-01-01

Type 1 (non neuronopathic) Gaucher disease was the first lysosomal storage disorder for which an effective enzyme replacement therapy was developed and it has become a prototype for treatments for related orphan diseases. There are currently four treatment options available to patients with Gaucher disease, nevertheless, almost 25% of type 1 Gaucher patients do not gain timely access to therapy because of delays in diagnosis after the onset of symptoms. Diagnosis of Gaucher disease by enzyme testing is unequivocal, but the rarity of the disease and non-specific and heterogeneous nature of Gaucher disease symptoms may impede consideration of this disease in the differential diagnosis. To help promote timely diagnosis and optimal management of the protean presentations of Gaucher disease, a consensus meeting was convened to develop algorithms for diagnosis and disease management for Gaucher disease. PMID:21080341

Massively parallel DNA sequencing facilitates diagnosis of patients with Usher syndrome type 1.

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Hidekane Yoshimura

Full Text Available Usher syndrome is an autosomal recessive disorder manifesting hearing loss, retinitis pigmentosa and vestibular dysfunction, and having three clinical subtypes. Usher syndrome type 1 is the most severe subtype due to its profound hearing loss, lack of vestibular responses, and retinitis pigmentosa that appears in prepuberty. Six of the corresponding genes have been identified, making early diagnosis through DNA testing possible, with many immediate and several long-term advantages for patients and their families. However, the conventional genetic techniques, such as direct sequence analysis, are both time-consuming and expensive. Targeted exon sequencing of selected genes using the massively parallel DNA sequencing technology will potentially enable us to systematically tackle previously intractable monogenic disorders and improve molecular diagnosis. Using this technique combined with direct sequence analysis, we screened 17 unrelated Usher syndrome type 1 patients and detected probable pathogenic variants in the 16 of them (94.1% who carried at least one mutation. Seven patients had the MYO7A mutation (41.2%, which is the most common type in Japanese. Most of the mutations were detected by only the massively parallel DNA sequencing. We report here four patients, who had probable pathogenic mutations in two different Usher syndrome type 1 genes, and one case of MYO7A/PCDH15 digenic inheritance. This is the first report of Usher syndrome mutation analysis using massively parallel DNA sequencing and the frequency of Usher syndrome type 1 genes in Japanese. Mutation screening using this technique has the power to quickly identify mutations of many causative genes while maintaining cost-benefit performance. In addition, the simultaneous mutation analysis of large numbers of genes is useful for detecting mutations in different genes that are possibly disease modifiers or of digenic inheritance.

Massively parallel DNA sequencing facilitates diagnosis of patients with Usher syndrome type 1.

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Yoshimura, Hidekane; Iwasaki, Satoshi; Nishio, Shin-Ya; Kumakawa, Kozo; Tono, Tetsuya; Kobayashi, Yumiko; Sato, Hiroaki; Nagai, Kyoko; Ishikawa, Kotaro; Ikezono, Tetsuo; Naito, Yasushi; Fukushima, Kunihiro; Oshikawa, Chie; Kimitsuki, Takashi; Nakanishi, Hiroshi; Usami, Shin-Ichi

2014-01-01

Usher syndrome is an autosomal recessive disorder manifesting hearing loss, retinitis pigmentosa and vestibular dysfunction, and having three clinical subtypes. Usher syndrome type 1 is the most severe subtype due to its profound hearing loss, lack of vestibular responses, and retinitis pigmentosa that appears in prepuberty. Six of the corresponding genes have been identified, making early diagnosis through DNA testing possible, with many immediate and several long-term advantages for patients and their families. However, the conventional genetic techniques, such as direct sequence analysis, are both time-consuming and expensive. Targeted exon sequencing of selected genes using the massively parallel DNA sequencing technology will potentially enable us to systematically tackle previously intractable monogenic disorders and improve molecular diagnosis. Using this technique combined with direct sequence analysis, we screened 17 unrelated Usher syndrome type 1 patients and detected probable pathogenic variants in the 16 of them (94.1%) who carried at least one mutation. Seven patients had the MYO7A mutation (41.2%), which is the most common type in Japanese. Most of the mutations were detected by only the massively parallel DNA sequencing. We report here four patients, who had probable pathogenic mutations in two different Usher syndrome type 1 genes, and one case of MYO7A/PCDH15 digenic inheritance. This is the first report of Usher syndrome mutation analysis using massively parallel DNA sequencing and the frequency of Usher syndrome type 1 genes in Japanese. Mutation screening using this technique has the power to quickly identify mutations of many causative genes while maintaining cost-benefit performance. In addition, the simultaneous mutation analysis of large numbers of genes is useful for detecting mutations in different genes that are possibly disease modifiers or of digenic inheritance.

Differential diagnosis of Jakob-Creutzfeldt disease.

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Paterson, Ross W; Torres-Chae, Charles C; Kuo, Amy L; Ando, Tim; Nguyen, Elizabeth A; Wong, Katherine; DeArmond, Stephen J; Haman, Aissa; Garcia, Paul; Johnson, David Y; Miller, Bruce L; Geschwind, Michael D

2012-12-01

To identify the misdiagnoses of patients with sporadic Jakob-Creutzfeldt disease (sCJD) during the course of their disease and determine which medical specialties saw patients with sCJD prior to the correct diagnosis being made and at what point in the disease course a correct diagnosis was made. Retrospective medical record review. A specialty referral center of a tertiary academic medical center. One hundred sixty-three serial patients over a 5.5-year period who ultimately had pathologically proven sCJD. The study used the subset of 97 patients for whom we had adequate medical records. Other diagnoses considered in the differential diagnosis and types of medical specialties assessing patients with sCJD. Ninety-seven subjects' records were used in the final analysis. The most common disease categories of misdiagnosis were neurodegenerative, autoimmune/paraneoplastic, infectious, and toxic/metabolic disorders. The most common individual misdiagnoses were viral encephalitis, paraneoplastic disorder, depression, vertigo, Alzheimer disease, stroke, unspecified dementia, central nervous system vasculitis, peripheral neuropathy, and Hashimoto encephalopathy. The physicians who most commonly made these misdiagnoses were primary care physicians and neurologists; in the 18% of patients who were diagnosed correctly at their first assessment, the diagnosis was almost always by a neurologist. The mean time from onset to diagnosis was 7.9 months, an average of two-thirds of the way through their disease course. Diagnosis of sCJD is quite delayed. When evaluating patients with rapidly progressive dementia with suspected neurodegenerative, autoimmune, infectious, or toxic/metabolic etiology, sCJD should also be included in the differential diagnosis, and appropriate diagnostic tests, such as diffusion brain magnetic resonance imaging, should be considered. Primary care physicians and neurologists need improved training in sCJD diagnosis.

Rare genetic diseases: update on diagnosis, treatment and online resources.

Science.gov (United States)

Pogue, Robert E; Cavalcanti, Denise P; Shanker, Shreya; Andrade, Rosangela V; Aguiar, Lana R; de Carvalho, Juliana L; Costa, Fabrício F

2018-01-01

Rare genetic diseases collectively impact a significant portion of the world's population. For many diseases there is limited information available, and clinicians can find difficulty in differentiating between clinically similar conditions. This leads to problems in genetic counseling and patient treatment. The biomedical market is affected because pharmaceutical and biotechnology industries do not see advantages in addressing rare disease treatments, or because the cost of the treatments is too high. By contrast, technological advances including DNA sequencing and analysis, together with computer-aided tools and online resources, are allowing a more thorough understanding of rare disorders. Here, we discuss how the collection of various types of information together with the use of new technologies is facilitating diagnosis and, consequently, treatment of rare diseases. Copyright © 2017 Elsevier Ltd. All rights reserved.

Massively parallel sequencing and targeted exomes in familial kidney disease can diagnose underlying genetic disorders.

Science.gov (United States)

Mallett, Andrew J; McCarthy, Hugh J; Ho, Gladys; Holman, Katherine; Farnsworth, Elizabeth; Patel, Chirag; Fletcher, Jeffery T; Mallawaarachchi, Amali; Quinlan, Catherine; Bennetts, Bruce; Alexander, Stephen I

2017-12-01

Inherited kidney disease encompasses a broad range of disorders, with both multiple genes contributing to specific phenotypes and single gene defects having multiple clinical presentations. Advances in sequencing capacity may allow a genetic diagnosis for familial renal disease, by testing the increasing number of known causative genes. However, there has been limited translation of research findings of causative genes into clinical settings. Here, we report the results of a national accredited diagnostic genetic service for familial renal disease. An expert multidisciplinary team developed a targeted exomic sequencing approach with ten curated multigene panels (207 genes) and variant assessment individualized to the patient's phenotype. A genetic diagnosis (pathogenic genetic variant[s]) was identified in 58 of 135 families referred in two years. The genetic diagnosis rate was similar between families with a pediatric versus adult proband (46% vs 40%), although significant differences were found in certain panels such as atypical hemolytic uremic syndrome (88% vs 17%). High diagnostic rates were found for Alport syndrome (22 of 27) and tubular disorders (8 of 10), whereas the monogenic diagnostic rate for congenital anomalies of the kidney and urinary tract was one of 13. Quality reporting was aided by a strong clinical renal and genetic multidisciplinary committee review. Importantly, for a diagnostic service, few variants of uncertain significance were found with this targeted, phenotype-based approach. Thus, use of targeted massively parallel sequencing approaches in inherited kidney disease has a significant capacity to diagnose the underlying genetic disorder across most renal phenotypes. Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

A targeted next-generation sequencing assay for the molecular diagnosis of genetic disorders with orodental involvement

Science.gov (United States)

Prasad, Megana K; Geoffroy, Véronique; Vicaire, Serge; Jost, Bernard; Dumas, Michael; Le Gras, Stéphanie; Switala, Marzena; Gasse, Barbara; Laugel-Haushalter, Virginie; Paschaki, Marie; Leheup, Bruno; Droz, Dominique; Dalstein, Amelie; Loing, Adeline; Grollemund, Bruno; Muller-Bolla, Michèle; Lopez-Cazaux, Séréna; Minoux, Maryline; Jung, Sophie; Obry, Frédéric; Vogt, Vincent; Davideau, Jean-Luc; Davit-Beal, Tiphaine; Kaiser, Anne-Sophie; Moog, Ute; Richard, Béatrice; Morrier, Jean-Jacques; Duprez, Jean-Pierre; Odent, Sylvie; Bailleul-Forestier, Isabelle; Rousset, Monique Marie; Merametdijan, Laure; Toutain, Annick; Joseph, Clara; Giuliano, Fabienne; Dahlet, Jean-Christophe; Courval, Aymeric; El Alloussi, Mustapha; Laouina, Samir; Soskin, Sylvie; Guffon, Nathalie; Dieux, Anne; Doray, Bérénice; Feierabend, Stephanie; Ginglinger, Emmanuelle; Fournier, Benjamin; de la Dure Molla, Muriel; Alembik, Yves; Tardieu, Corinne; Clauss, François; Berdal, Ariane; Stoetzel, Corinne; Manière, Marie Cécile; Dollfus, Hélène; Bloch-Zupan, Agnès

2016-01-01

Background Orodental diseases include several clinically and genetically heterogeneous disorders that can present in isolation or as part of a genetic syndrome. Due to the vast number of genes implicated in these disorders, establishing a molecular diagnosis can be challenging. We aimed to develop a targeted next-generation sequencing (NGS) assay to diagnose mutations and potentially identify novel genes mutated in this group of disorders. Methods We designed an NGS gene panel that targets 585 known and candidate genes in orodental disease. We screened a cohort of 101 unrelated patients without a molecular diagnosis referred to the Reference Centre for Oro-Dental Manifestations of Rare Diseases, Strasbourg, France, for a variety of orodental disorders including isolated and syndromic amelogenesis imperfecta (AI), isolated and syndromic selective tooth agenesis (STHAG), isolated and syndromic dentinogenesis imperfecta, isolated dentin dysplasia, otodental dysplasia and primary failure of tooth eruption. Results We discovered 21 novel pathogenic variants and identified the causative mutation in 39 unrelated patients in known genes (overall diagnostic rate: 39%). Among the largest subcohorts of patients with isolated AI (50 unrelated patients) and isolated STHAG (21 unrelated patients), we had a definitive diagnosis in 14 (27%) and 15 cases (71%), respectively. Surprisingly, COL17A1 mutations accounted for the majority of autosomal-dominant AI cases. Conclusions We have developed a novel targeted NGS assay for the efficient molecular diagnosis of a wide variety of orodental diseases. Furthermore, our panel will contribute to better understanding the contribution of these genes to orodental disease. Trial registration numbers NCT01746121 and NCT02397824. PMID:26502894

The Role of Next-Generation Sequencing in the Diagnosis of Lysosomal Storage Disorders

Directory of Open Access Journals (Sweden)

Katalin Komlosi MD, PhD

2016-10-01

Full Text Available Next-generation sequencing (NGS panels are used widely in clinical diagnostics to identify genetic causes of various monogenic disease groups including neurometabolic disorders and, more recently, lysosomal storage disorders (LSDs. Many new challenges have been introduced through these new technologies, both at the laboratory level and at the bioinformatics level, with consequences including new requirements for interpretation of results, and for genetic counseling. We review some recent examples of the application of NGS technologies, with purely diagnostic and with both diagnostic and research aims, for establishing a rapid genetic diagnosis in LSDs. Given that NGS can be applied in a way that takes into account the many issues raised by international consensus guidelines, it can have a significant role even early in the course of the diagnostic process, in combination with biochemical and clinical data. Besides decreasing the delay in diagnosis for many patients, a precise molecular diagnosis is extremely important as new therapies are becoming available within the LSD spectrum for patients who share specific types of mutations. A genetic diagnosis is also the prerequisite for genetic counseling, family planning, and the individual choice of reproductive options in affected families.

The clinical application of genome-wide sequencing for monogenic diseases in Canada: Position Statement of the Canadian College of Medical Geneticists

OpenAIRE

Boycott, Kym; Hartley, Taila; Adam, Shelin; Bernier, Francois; Chong, Karen; Fernandez, Bridget A; Friedman, Jan M; Geraghty, Michael T; Hume, Stacey; Knoppers, Bartha M; Laberge, Anne-Marie; Majewski, Jacek; Mendoza-Londono, Roberto; Meyn, M Stephen; Michaud, Jacques L

2015-01-01

Purpose and scope The aim of this Position Statement is to provide recommendations for Canadian medical geneticists, clinical laboratory geneticists, genetic counsellors and other physicians regarding the use of genome-wide sequencing of germline DNA in the context of clinical genetic diagnosis. This statement has been developed to facilitate the clinical translation and development of best practices for clinical genome-wide sequencing for genetic diagnosis of monogenic diseases in Canada; it...

Genotype, phenotype and in silico pathogenicity analysis of HEXB mutations: Panel based sequencing for differential diagnosis of gangliosidosis.

Science.gov (United States)

Mahdieh, Nejat; Mikaeeli, Sahar; Tavasoli, Ali Reza; Rezaei, Zahra; Maleki, Majid; Rabbani, Bahareh

2018-04-01

Gangliosidosis is an inherited metabolic disorder causing neurodegeneration and motor regression. Preventive diagnosis is the first choice for the affected families due to lack of straightforward therapy. Genetic studies could confirm the diagnosis and help families for carrier screening and prenatal diagnosis. An update of HEXB gene variants concerning genotype, phenotype and in silico analysis are presented. Panel based next generation sequencing and direct sequencing of four cases were performed to confirm the clinical diagnosis and for reproductive planning. Bioinformatic analyses of the HEXB mutation database were also performed. Direct sequencing of HEXA and HEXB genes showed recurrent homozygous variants at c.509G>A (p.Arg170Gln) and c.850C>T (p.Arg284Ter), respectively. A novel variant at c.416T>A (p.Leu139Gln) was identified in the GLB1 gene. Panel based next generation sequencing was performed for an undiagnosed patient which showed a novel mutation at c.1602C>A (p.Cys534Ter) of HEXB gene. Bioinformatic analysis of the HEXB mutation database showed 97% consistency of in silico genotype analysis with the phenotype. Bioinformatic analysis of the novel variants predicted to be disease causing. In silico structural and functional analysis of the novel variants showed structural effect of HEXB and functional effect of GLB1 variants which would provide fast analysis of novel variants. Panel based studies could be performed for overlapping symptomatic patients. Consequently, genetic testing would help affected families for patients' management, carrier detection, and family planning's. Copyright © 2018 Elsevier B.V. All rights reserved.

Computer-assisted initial diagnosis of rare diseases

Directory of Open Access Journals (Sweden)

Rui Alves

2016-07-01

Full Text Available Introduction. Most documented rare diseases have genetic origin. Because of their low individual frequency, an initial diagnosis based on phenotypic symptoms is not always easy, as practitioners might never have been exposed to patients suffering from the relevant disease. It is thus important to develop tools that facilitate symptom-based initial diagnosis of rare diseases by clinicians. In this work we aimed at developing a computational approach to aid in that initial diagnosis. We also aimed at implementing this approach in a user friendly web prototype. We call this tool Rare Disease Discovery. Finally, we also aimed at testing the performance of the prototype. Methods. Rare Disease Discovery uses the publicly available ORPHANET data set of association between rare diseases and their symptoms to automatically predict the most likely rare diseases based on a patient’s symptoms. We apply the method to retrospectively diagnose a cohort of 187 rare disease patients with confirmed diagnosis. Subsequently we test the precision, sensitivity, and global performance of the system under different scenarios by running large scale Monte Carlo simulations. All settings account for situations where absent and/or unrelated symptoms are considered in the diagnosis. Results. We find that this expert system has high diagnostic precision (≥80% and sensitivity (≥99%, and is robust to both absent and unrelated symptoms. Discussion. The Rare Disease Discovery prediction engine appears to provide a fast and robust method for initial assisted differential diagnosis of rare diseases. We coupled this engine with a user-friendly web interface and it can be freely accessed at http://disease-discovery.udl.cat/. The code and most current database for the whole project can be downloaded from https://github.com/Wrrzag/DiseaseDiscovery/tree/no_classifiers.

Nonculture molecular techniques for diagnosis of bacterial disease in animals: a diagnostic laboratory perspective.

Science.gov (United States)

Cai, H Y; Caswell, J L; Prescott, J F

2014-03-01

The past decade has seen remarkable technical advances in infectious disease diagnosis, and the pace of innovation is likely to continue. Many of these techniques are well suited to pathogen identification directly from pathologic or clinical samples, which is the focus of this review. Polymerase chain reaction (PCR) and gene sequencing are now routinely performed on frozen or fixed tissues for diagnosis of bacterial infections of animals. These assays are most useful for pathogens that are difficult to culture or identify phenotypically, when propagation poses a biosafety hazard, or when suitable fresh tissue is not available. Multiplex PCR assays, DNA microarrays, in situ hybridization, massive parallel DNA sequencing, microbiome profiling, molecular typing of pathogens, identification of antimicrobial resistance genes, and mass spectrometry are additional emerging technologies for the diagnosis of bacterial infections from pathologic and clinical samples in animals. These technical advances come, however, with 2 caveats. First, in the age of molecular diagnosis, quality control has become more important than ever to identify and control for the presence of inhibitors, cross-contamination, inadequate templates from diagnostic specimens, and other causes of erroneous microbial identifications. Second, the attraction of these technologic advances can obscure the reality that medical diagnoses cannot be made on the basis of molecular testing alone but instead through integrated consideration of clinical, pathologic, and laboratory findings. Proper validation of the method is required. It is critical that veterinary diagnosticians understand not only the value but also the limitations of these technical advances for routine diagnosis of infectious disease.

Utility of whole exome sequencing in the diagnosis of Usher syndrome: Report of novel compound heterozygous MYO7A mutations.

Science.gov (United States)

Ramzan, Khushnooda; Al-Owain, Mohammed; Huma, Rozeena; Al-Hazzaa, Selwa A F; Al-Ageel, Sarah; Imtiaz, Faiqa; Al-Sayed, Moeenaldeen

2018-05-01

Next generation sequencing (NGS), such as targeted panel sequencing, whole-exome sequencing and whole-genome sequencing has led to an exponential increase of elucidated genetic causes in both rare diseases, and common but heterogeneous disorders. NGS is applied in both research and clinical settings, and the clinical exome sequencing (CES), which provides not only the sequence variation data but also clinical interpretation, aids in reaching a final conclusion with regards to a genetic diagnosis. Usher syndrome is a group of disorders, characterized by bilateral sensorineural hearing loss, with or without vestibular dysfunction and retinitis pigmentosa. The index patient, a 2-year-old child was initially diagnosed with nonsyndromic hearing impairment. Homozygosity mapping followed by CES was utilized as a diagnostic tool to identify the genetic basis of his hearing loss. A paternally inherited novel insertion, c.198_199insA (p.Val67Serfs*73) and a maternally inherited novel deletion, c.1219_1226del (p.Phe407Aspfs*33) in gene MYO7A were found in compound heterozygous state in the index patient. The result expands the mutational spectrum of MYO7A. In addition it helped in early diagnosis of the syndrome, for planning and adjustments for the patient, and as well as for future family planning. This study highlights the clinical effectiveness of CES for Usher syndrome diagnosis in a child presented with congenital hearing loss. Copyright © 2018. Published by Elsevier B.V.

Differential diagnosis of Jakob-Creutzfeldt disease

OpenAIRE

Paterson, RW; Torres-Chae, CC; Kuo, AL; Ando, T; Nguyen, EA; Wong, K; DeArmond, SJ; Haman, A; Garcia, P; Johnson, DY; Miller, BL; Geschwind, MD

2012-01-01

Objectives: To identify the misdiagnoses of patients with sporadic Jakob-Creutzfeldt disease (sCJD) during the course of their disease and determine which medical specialties saw patients with sCJD prior to the correct diagnosis being made and at what point in the disease course a correct diagnosis was made. Design: Retrospective medical record review. Setting: A specialty referral center of a tertiary academic medical center. Participants: One hundred sixty-three serial patients over a 5.5-y...

Targeted next-generation sequencing reveals novel USH2A mutations associated with diverse disease phenotypes: implications for clinical and molecular diagnosis.

Science.gov (United States)

Chen, Xue; Sheng, Xunlun; Liu, Xiaoxing; Li, Huiping; Liu, Yani; Rong, Weining; Ha, Shaoping; Liu, Wenzhou; Kang, Xiaoli; Zhao, Kanxing; Zhao, Chen

2014-01-01

USH2A mutations have been implicated in the disease etiology of several inherited diseases, including Usher syndrome type 2 (USH2), nonsyndromic retinitis pigmentosa (RP), and nonsyndromic deafness. The complex genetic and phenotypic spectrums relevant to USH2A defects make it difficult to manage patients with such mutations. In the present study, we aim to determine the genetic etiology and to characterize the correlated clinical phenotypes for three Chinese pedigrees with nonsyndromic RP, one with RP sine pigmento (RPSP), and one with USH2. Family histories and clinical details for all included patients were reviewed. Ophthalmic examinations included best corrected visual acuities, visual field measurements, funduscopy, and electroretinography. Targeted next-generation sequencing (NGS) was applied using two sequence capture arrays to reveal the disease causative mutations for each family. Genotype-phenotype correlations were also annotated. Seven USH2A mutations, including four missense substitutions (p.P2762A, p.G3320C, p.R3719H, and p.G4763R), two splice site variants (c.8223+1G>A and c.8559-2T>C), and a nonsense mutation (p.Y3745*), were identified as disease causative in the five investigated families, of which three reported to have consanguineous marriage. Among all seven mutations, six were novel, and one was recurrent. Two homozygous missense mutations (p.P2762A and p.G3320C) were found in one individual family suggesting a potential double hit effect. Significant phenotypic divergences were revealed among the five families. Three families of the five families were affected with early, moderated, or late onset RP, one with RPSP, and the other one with USH2. Our study expands the genotypic and phenotypic variability relevant to USH2A mutations, which would help with a clear insight into the complex genetic and phenotypic spectrums relevant to USH2A defects, and is complementary for a better management of patients with such mutations. We have also

Complete exon sequencing of all known Usher syndrome genes greatly improves molecular diagnosis.

Science.gov (United States)

Bonnet, Crystel; Grati, M'hamed; Marlin, Sandrine; Levilliers, Jacqueline; Hardelin, Jean-Pierre; Parodi, Marine; Niasme-Grare, Magali; Zelenika, Diana; Délépine, Marc; Feldmann, Delphine; Jonard, Laurence; El-Amraoui, Aziz; Weil, Dominique; Delobel, Bruno; Vincent, Christophe; Dollfus, Hélène; Eliot, Marie-Madeleine; David, Albert; Calais, Catherine; Vigneron, Jacqueline; Montaut-Verient, Bettina; Bonneau, Dominique; Dubin, Jacques; Thauvin, Christel; Duvillard, Alain; Francannet, Christine; Mom, Thierry; Lacombe, Didier; Duriez, Françoise; Drouin-Garraud, Valérie; Thuillier-Obstoy, Marie-Françoise; Sigaudy, Sabine; Frances, Anne-Marie; Collignon, Patrick; Challe, Georges; Couderc, Rémy; Lathrop, Mark; Sahel, José-Alain; Weissenbach, Jean; Petit, Christine; Denoyelle, Françoise

2011-05-11

Usher syndrome (USH) combines sensorineural deafness with blindness. It is inherited in an autosomal recessive mode. Early diagnosis is critical for adapted educational and patient management choices, and for genetic counseling. To date, nine causative genes have been identified for the three clinical subtypes (USH1, USH2 and USH3). Current diagnostic strategies make use of a genotyping microarray that is based on the previously reported mutations. The purpose of this study was to design a more accurate molecular diagnosis tool. We sequenced the 366 coding exons and flanking regions of the nine known USH genes, in 54 USH patients (27 USH1, 21 USH2 and 6 USH3). Biallelic mutations were detected in 39 patients (72%) and monoallelic mutations in an additional 10 patients (18.5%). In addition to biallelic mutations in one of the USH genes, presumably pathogenic mutations in another USH gene were detected in seven patients (13%), and another patient carried monoallelic mutations in three different USH genes. Notably, none of the USH3 patients carried detectable mutations in the only known USH3 gene, whereas they all carried mutations in USH2 genes. Most importantly, the currently used microarray would have detected only 30 of the 81 different mutations that we found, of which 39 (48%) were novel. Based on these results, complete exon sequencing of the currently known USH genes stands as a definite improvement for molecular diagnosis of this disease, which is of utmost importance in the perspective of gene therapy.

Complete exon sequencing of all known Usher syndrome genes greatly improves molecular diagnosis

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Lacombe Didier

2011-05-01

Full Text Available Abstract Background Usher syndrome (USH combines sensorineural deafness with blindness. It is inherited in an autosomal recessive mode. Early diagnosis is critical for adapted educational and patient management choices, and for genetic counseling. To date, nine causative genes have been identified for the three clinical subtypes (USH1, USH2 and USH3. Current diagnostic strategies make use of a genotyping microarray that is based on the previously reported mutations. The purpose of this study was to design a more accurate molecular diagnosis tool. Methods We sequenced the 366 coding exons and flanking regions of the nine known USH genes, in 54 USH patients (27 USH1, 21 USH2 and 6 USH3. Results Biallelic mutations were detected in 39 patients (72% and monoallelic mutations in an additional 10 patients (18.5%. In addition to biallelic mutations in one of the USH genes, presumably pathogenic mutations in another USH gene were detected in seven patients (13%, and another patient carried monoallelic mutations in three different USH genes. Notably, none of the USH3 patients carried detectable mutations in the only known USH3 gene, whereas they all carried mutations in USH2 genes. Most importantly, the currently used microarray would have detected only 30 of the 81 different mutations that we found, of which 39 (48% were novel. Conclusions Based on these results, complete exon sequencing of the currently known USH genes stands as a definite improvement for molecular diagnosis of this disease, which is of utmost importance in the perspective of gene therapy.

[Using exon combined target region capture sequencing chip to detect the disease-causing genes of retinitis pigmentosa].

Science.gov (United States)

Rong, Weining; Chen, Xuejuan; Li, Huiping; Liu, Yani; Sheng, Xunlun

2014-06-01

To detect the disease-causing genes of 10 retinitis pigmentosa pedigrees by using exon combined target region capture sequencing chip. Pedigree investigation study. From October 2010 to December 2013, 10 RP pedigrees were recruited for this study in Ningxia Eye Hospital. All the patients and family members received complete ophthalmic examinations. DNA was abstracted from patients, family members and controls. Using exon combined target region capture sequencing chip to screen the candidate disease-causing mutations. Polymerase chain reaction (PCR) and direct sequencing were used to confirm the disease-causing mutations. Seventy patients and 23 normal family members were recruited from 10 pedigrees. Among 10 RP pedigrees, 1 was autosomal dominant pedigrees and 9 were autosomal recessive pedigrees. 7 mutations related to 5 genes of 5 pedigrees were detected. A frameshift mutation on BBS7 gene was detected in No.2 pedigree, the patients of this pedigree combined with central obesity, polydactyly and mental handicap. No.2 pedigree was diagnosed as Bardet-Biedl syndrome finally. A missense mutation was detected in No.7 and No.10 pedigrees respectively. Because the patients suffered deafness meanwhile, the final diagnosis was Usher syndrome. A missense mutation on C3 gene related to age-related macular degeneration was also detected in No. 7 pedigrees. A nonsense mutation and a missense mutation on CRB1 gene were detected in No. 1 pedigree and a splicesite mutation on PROM1 gene was detected in No. 5 pedigree. Retinitis pigmentosa is a kind of genetic eye disease with diversity clinical phenotypes. Rapid and effective genetic diagnosis technology combined with clinical characteristics analysis is helpful to improve the level of clinical diagnosis of RP.

Charcot-Marie-Tooth disease: The development of a diagnostic platform using next generation sequencing

DEFF Research Database (Denmark)

Christensen, Rikke; Væth, Signe; Thorsen, Kasper

, Sanger sequencing of 4 genes have led to a diagnosis in approximately 30% of the patients. Aims: 1) Development of a targeted NGS platform containing 63 genes that currently are found to be associated with CMT. 2) Analysis of the increased diagnostic yield using this platform to analyze 200 CMT samples...... previously analyzed using Sanger sequencing without identification of a disease causing mutation. Materials and Methods: Libraries for 200 patient samples obtained for CMT diagnostics were prepared using Illumina Truseq and target enrichment using SeqCap EZ Choise Library (Nimblegen). The libraries were...

Diagnosis of Nocardia paucivorans central nervous system infection by DNA sequencing from paraffin-embedded tissue.

Science.gov (United States)

Schiaroli, Elisabetta; Pasticci, Maria Bruna; De Carolis, Elena; Mello, Enrica; Pallotto, Carlo; Leli, Christian; De Socio, Giuseppe Vittorio; Baldelli, Franco; Sanguinetti, Maurizio; Mencacci, Antonella

2016-06-01

Infections by Nocardia spp. are generally regarded as opportunistic diseases in immunocompromised patients, but can also affect immunocompetent subjects. Such infections represent an important diagnostic challenge for clinicians and microbiologists, and diagnosis is frequently delayed or even conducted post mortem. A 54-year-old man was admitted to our hospital because of ventriculitis and relapsing brain abscess. Five months prior, this patient had undergone external ventricular drain and surgery for a cerebellar abscess. Histopathology demonstrated pyogenic inflammatory reaction, microbiologic investigations proved negative and empiric antimicrobial therapy was administered for a total of eight weeks. Six weeks later, the patient developed relapsing neurologic manifestations. On reviewing the patient's clinical history it emerged that the patient had suffered pneumonia two months prior to neurosurgery, treated with amoxicillin/clavulanate 3g a day and levofloxacin 500mg a day for three weeks. On the CNS relapsing manifestations, nocardiosis was suspected and DNA sequencing from the formalin-fixed paraffin-embedded cerebellar tissue collected during neurosurgery allowed diagnosis of Nocardia paucivorans infection. The patient received medical therapy for 11 months. At follow-up, eight months after treatment was discontinued, the patient was aymptomatic. Nocardia spp. infections need to be suspected not only in immunocompromised, but also in immunocompetent patients. Proper samples need to be collected for proper microbiologic investigations. Paraffin-embedded tissue genomic sequencing can be a useful tool for diagnosis of nocardiosis.

Parkinson's Disease: Diagnosis and Treatment

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... of this page please turn JavaScript on. Feature: Parkinson's Disease Parkinson's Disease: Diagnosis and Treatment Past Issues / Winter 2014 ... live productive lives and maintain mobility. How is Parkinson's Diagnosed? There are no blood or laboratory tests ...

Diagnosis of animal diseases using nuclear and related techniques: Developments and trends

International Nuclear Information System (INIS)

Anderson, J.; McKay, J.A.

1991-01-01

Nuclear techniques such as radioimmune precipitation, radioimmunoassay, DNA cloning and amino acid sequencing have led to a greater understanding of protein structure and function, antigenic variation and the immune response to infection. Knowledge gained from the use of this technology has led to the development of improved diagnostic assays. Although radioimmunoassay has been used for animal disease diagnosis for many years, more recently it has been replaced by the enzyme linked immunosorbent assay (ELISA). The ELISA offers advantages in speed of reading and longer reagent shelf life and obviates the use of radiochemicals. This is particularly important in developing countries, which may have no facilities for storage, handling and disposal of radioactive materials. In the case of rinderpest diagnosis, taken as an example, the virus neutralization test was replaced by a simple indirect ELISA for seromonitoring throughout the Pan-African Rinderpest Campaign. In the near future, this will be replaced by a competitive ELISA using a rinderpest specific monoclonal antibody, which will offer significant advantages in sensitivity and specificity. In the future it may be possible to replace the rinderpest antigen with vector expressed proteins or synthetic polypeptides. More recent developments such as the 'amplified' ELISA and the use of fluorogenic and bioluminescent substrates may further improve disease diagnosis. The knowledge gained from the use of modern technology is essential to the development of improved diagnostic assays which in turn will lead to improved disease diagnosis and control. (author). 9 refs

HDP2: a ribosomal DNA (NTS-ETS) sequence as a target for species-specific molecular diagnosis of intestinal taeniasis in humans.

Science.gov (United States)

Flores, María D; Gonzalez, Luis M; Hurtado, Carolina; Motta, Yamileth Monje; Domínguez-Hidalgo, Cristina; Merino, Francisco Jesús; Perteguer, María J; Gárate, Teresa

2018-02-27

Taenia solium, T. asiatica and T. saginata tapeworms cause human taeniasis and are the origin of porcine and bovine cysticercosis. Furthermore, T. solium eggs can cause human cysticercosis, with neurocysticercosis being the most serious form of the disease. These helminth infections are neglected tropical diseases and are endemic in several countries in the Americas, Asia and Africa. As a result of globalization, migration in particular, the infections have been extending to non-endemic territories. Species-specific diagnosis of taeniasis is subject to drawbacks that could be resolved using molecular approaches. In the present study, conventional and real-time amplification protocols (cPCR and qPCR) based on the T. saginata HDP2 sequence were applied in the differential diagnosis of taeniasis (T. saginata, T. solium) in both fecal samples and proglottids expelled by patients. The HDP2 homolog in T. solium was cloned and characterized. Semi-nested cPCR and qPCR (Sn-HDP2 cPCR and Sn-HDP2 qPCR) amplified T. saginata and T. solium DNA, with an analytical sensitivity of 40 and 400 fg, respectively, and identically in both protocols. Eighteen taeniasis patients were diagnosed directly with T. saginata or T. solium, either from proglottids or fecal samples with/without eggs (detected using microscopy), based on the optimized Sn-HDP2 qPCR. After cloning, the T. solium HDP2 homolog sequence was confirmed to be a ribosomal sequence. The HDP2 fragment corresponded to a non-transcribed sequence/external transcribed repeat (NTS/ETS) of ribosomal DNA. Compared with the T. saginata HDP2 homolog, the T solium HDP2 sequence lacked the first 900 nt at the 5' end and showed nucleotide substitutions and small deletions. Sn-HDP2 cPCR and Sn-HDP2 qPCR were set up for the diagnosis of human taeniasis, using proglottids and fecal samples from affected patients. The new Sn-HDP2 qPCR protocol was the best option, as it directly differentiated T. saginata from T. solium. The diagnosis of

Transcranial Ultrasound in the Diagnosis of Parkinson’s Disease

Directory of Open Access Journals (Sweden)

Aniley Martínez González

2014-10-01

Full Text Available Parkinson’s disease is the second most common neurodegenerative disorder and, since it is associated with aging, the probability of developing this disease increases with age. The diagnosis of idiopathic Parkinson’s disease is based on clinical criteria; however, its differentiation from other forms of Parkinsonism can be difficult, especially in early stages of the disease. Transcranial ultrasound has become a tool for the diagnosis of this disorder, being very useful for its early diagnosis. Ultrasonographic findings characteristic of this disease include increased echogenicity of the substantia nigra in the midbrain measured through the temporal bone window. This paper discusses the usefulness of transcranial ultrasound for early diagnosis of patients with Parkinson's disease.

The clinical application of genome-wide sequencing for monogenic diseases in Canada: Position Statement of the Canadian College of Medical Geneticists

Science.gov (United States)

Boycott, Kym; Hartley, Taila; Adam, Shelin; Bernier, Francois; Chong, Karen; Fernandez, Bridget A; Friedman, Jan M; Geraghty, Michael T; Hume, Stacey; Knoppers, Bartha M; Laberge, Anne-Marie; Majewski, Jacek; Mendoza-Londono, Roberto; Meyn, M Stephen; Michaud, Jacques L; Nelson, Tanya N; Richer, Julie; Sadikovic, Bekim; Skidmore, David L; Stockley, Tracy; Taylor, Sherry; van Karnebeek, Clara; Zawati, Ma'n H; Lauzon, Julie; Armour, Christine M

2015-01-01

Purpose and scope The aim of this Position Statement is to provide recommendations for Canadian medical geneticists, clinical laboratory geneticists, genetic counsellors and other physicians regarding the use of genome-wide sequencing of germline DNA in the context of clinical genetic diagnosis. This statement has been developed to facilitate the clinical translation and development of best practices for clinical genome-wide sequencing for genetic diagnosis of monogenic diseases in Canada; it does not address the clinical application of this technology in other fields such as molecular investigation of cancer or for population screening of healthy individuals. Methods of statement development Two multidisciplinary groups consisting of medical geneticists, clinical laboratory geneticists, genetic counsellors, ethicists, lawyers and genetic researchers were assembled to review existing literature and guidelines on genome-wide sequencing for clinical genetic diagnosis in the context of monogenic diseases, and to make recommendations relevant to the Canadian context. The statement was circulated for comment to the Canadian College of Medical Geneticists (CCMG) membership-at-large and, following incorporation of feedback, approved by the CCMG Board of Directors. The CCMG is a Canadian organisation responsible for certifying medical geneticists and clinical laboratory geneticists, and for establishing professional and ethical standards for clinical genetics services in Canada. Results and conclusions Recommendations include (1) clinical genome-wide sequencing is an appropriate approach in the diagnostic assessment of a patient for whom there is suspicion of a significant monogenic disease that is associated with a high degree of genetic heterogeneity, or where specific genetic tests have failed to provide a diagnosis; (2) until the benefits of reporting incidental findings are established, we do not endorse the intentional clinical analysis of disease-associated genes

The clinical application of genome-wide sequencing for monogenic diseases in Canada: Position Statement of the Canadian College of Medical Geneticists.

Science.gov (United States)

Boycott, Kym; Hartley, Taila; Adam, Shelin; Bernier, Francois; Chong, Karen; Fernandez, Bridget A; Friedman, Jan M; Geraghty, Michael T; Hume, Stacey; Knoppers, Bartha M; Laberge, Anne-Marie; Majewski, Jacek; Mendoza-Londono, Roberto; Meyn, M Stephen; Michaud, Jacques L; Nelson, Tanya N; Richer, Julie; Sadikovic, Bekim; Skidmore, David L; Stockley, Tracy; Taylor, Sherry; van Karnebeek, Clara; Zawati, Ma'n H; Lauzon, Julie; Armour, Christine M

2015-07-01

The aim of this Position Statement is to provide recommendations for Canadian medical geneticists, clinical laboratory geneticists, genetic counsellors and other physicians regarding the use of genome-wide sequencing of germline DNA in the context of clinical genetic diagnosis. This statement has been developed to facilitate the clinical translation and development of best practices for clinical genome-wide sequencing for genetic diagnosis of monogenic diseases in Canada; it does not address the clinical application of this technology in other fields such as molecular investigation of cancer or for population screening of healthy individuals. Two multidisciplinary groups consisting of medical geneticists, clinical laboratory geneticists, genetic counsellors, ethicists, lawyers and genetic researchers were assembled to review existing literature and guidelines on genome-wide sequencing for clinical genetic diagnosis in the context of monogenic diseases, and to make recommendations relevant to the Canadian context. The statement was circulated for comment to the Canadian College of Medical Geneticists (CCMG) membership-at-large and, following incorporation of feedback, approved by the CCMG Board of Directors. The CCMG is a Canadian organisation responsible for certifying medical geneticists and clinical laboratory geneticists, and for establishing professional and ethical standards for clinical genetics services in Canada. Recommendations include (1) clinical genome-wide sequencing is an appropriate approach in the diagnostic assessment of a patient for whom there is suspicion of a significant monogenic disease that is associated with a high degree of genetic heterogeneity, or where specific genetic tests have failed to provide a diagnosis; (2) until the benefits of reporting incidental findings are established, we do not endorse the intentional clinical analysis of disease-associated genes other than those linked to the primary indication; and (3) clinicians should

Genetic architecture of retinal and macular degenerative diseases: the promise and challenges of next-generation sequencing

Science.gov (United States)

2013-01-01

Inherited retinal degenerative diseases (RDDs) display wide variation in their mode of inheritance, underlying genetic defects, age of onset, and phenotypic severity. Molecular mechanisms have not been delineated for many retinal diseases, and treatment options are limited. In most instances, genotype-phenotype correlations have not been elucidated because of extensive clinical and genetic heterogeneity. Next-generation sequencing (NGS) methods, including exome, genome, transcriptome and epigenome sequencing, provide novel avenues towards achieving comprehensive understanding of the genetic architecture of RDDs. Whole-exome sequencing (WES) has already revealed several new RDD genes, whereas RNA-Seq and ChIP-Seq analyses are expected to uncover novel aspects of gene regulation and biological networks that are involved in retinal development, aging and disease. In this review, we focus on the genetic characterization of retinal and macular degeneration using NGS technology and discuss the basic framework for further investigations. We also examine the challenges of NGS application in clinical diagnosis and management. PMID:24112618

Next-Generation Sequencing in Neuropathologic Diagnosis of Infections of the Nervous System (Open Access)

Science.gov (United States)

2016-06-13

nervous system ABSTRACT Objective: To determine the feasibility of next-generation sequencing (NGS) microbiome ap- proaches in the diagnosis of infectious...V, van Doorn HR, Nghia HD, et al. Identification of a new cyclovirus in cerebrospinal fluid of patients with acute central nervous system infections...Kumar, et al. system Next-generation sequencing in neuropathologic diagnosis of infections of the nervous This information is current as of June 13

Whole-genome sequencing of multiple myeloma from diagnosis to plasma cell leukemia reveals genomic initiating events, evolution, and clonal tides.

Science.gov (United States)

Egan, Jan B; Shi, Chang-Xin; Tembe, Waibhav; Christoforides, Alexis; Kurdoglu, Ahmet; Sinari, Shripad; Middha, Sumit; Asmann, Yan; Schmidt, Jessica; Braggio, Esteban; Keats, Jonathan J; Fonseca, Rafael; Bergsagel, P Leif; Craig, David W; Carpten, John D; Stewart, A Keith

2012-08-02

The longitudinal evolution of a myeloma genome from diagnosis to plasma cell leukemia has not previously been reported. We used whole-genome sequencing (WGS) on 4 purified tumor samples and patient germline DNA drawn over a 5-year period in a t(4;14) multiple myeloma patient. Tumor samples were acquired at diagnosis, first relapse, second relapse, and end-stage secondary plasma cell leukemia (sPCL). In addition to the t(4;14), all tumor time points also shared 10 common single-nucleotide variants (SNVs) on WGS comprising shared initiating events. Interestingly, we observed genomic sequence variants that waxed and waned with time in progressive tumors, suggesting the presence of multiple independent, yet related, clones at diagnosis that rose and fell in dominance. Five newly acquired SNVs, including truncating mutations of RB1 and ZKSCAN3, were observed only in the final sPCL sample suggesting leukemic transformation events. This longitudinal WGS characterization of the natural history of a high-risk myeloma patient demonstrated tumor heterogeneity at diagnosis with shifting dominance of tumor clones over time and has also identified potential mutations contributing to myelomagenesis as well as transformation from myeloma to overt extramedullary disease such as sPCL.

Addison's disease - the difficulty of diagnosis

Directory of Open Access Journals (Sweden)

Clara Preto

2018-04-01

Full Text Available Introduction: Primary adrenal insufficiency is a rare disease, especially in pediatric age. Case report: We report the case of a teenager with astenia with four months’ evolution, causing repeated visits to the emergency department during the previous month due gastrointestinal symptoms and a ten kilograms weight loss. In admission the patient had a reasonable general condition, hydrated and without cutaneous hyperpigmentation. Laboratory results showed hyponatremia, increased levels of corticotropin with normal cortisol levels, increased levels of renin with decreased aldosterone levels and presence of antissuprarrenal antibodies, allowing the diagnosis of autoimmune primary adrenal insufficiency. The boy started treatment with hydrocortisone and fludrocortisone with favorable response. Discussion/conclusions: The diagnosis of Addison’s disease requires a high degree of suspicion due its unspecific symptomatology. This disease often presents gastrointestinal symptoms. Thus, towards a patient with hyponatremia accompanied by constitutional and gastrointestinal symptoms, we must always consider this diagnosis.

Targeted next-generation sequencing reveals novel USH2A mutations associated with diverse disease phenotypes: implications for clinical and molecular diagnosis.

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Xue Chen

Full Text Available USH2A mutations have been implicated in the disease etiology of several inherited diseases, including Usher syndrome type 2 (USH2, nonsyndromic retinitis pigmentosa (RP, and nonsyndromic deafness. The complex genetic and phenotypic spectrums relevant to USH2A defects make it difficult to manage patients with such mutations. In the present study, we aim to determine the genetic etiology and to characterize the correlated clinical phenotypes for three Chinese pedigrees with nonsyndromic RP, one with RP sine pigmento (RPSP, and one with USH2. Family histories and clinical details for all included patients were reviewed. Ophthalmic examinations included best corrected visual acuities, visual field measurements, funduscopy, and electroretinography. Targeted next-generation sequencing (NGS was applied using two sequence capture arrays to reveal the disease causative mutations for each family. Genotype-phenotype correlations were also annotated. Seven USH2A mutations, including four missense substitutions (p.P2762A, p.G3320C, p.R3719H, and p.G4763R, two splice site variants (c.8223+1G>A and c.8559-2T>C, and a nonsense mutation (p.Y3745*, were identified as disease causative in the five investigated families, of which three reported to have consanguineous marriage. Among all seven mutations, six were novel, and one was recurrent. Two homozygous missense mutations (p.P2762A and p.G3320C were found in one individual family suggesting a potential double hit effect. Significant phenotypic divergences were revealed among the five families. Three families of the five families were affected with early, moderated, or late onset RP, one with RPSP, and the other one with USH2. Our study expands the genotypic and phenotypic variability relevant to USH2A mutations, which would help with a clear insight into the complex genetic and phenotypic spectrums relevant to USH2A defects, and is complementary for a better management of patients with such mutations. We have

Conservation of nucleotide sequences for molecular diagnosis of Middle East respiratory syndrome coronavirus, 2015

Directory of Open Access Journals (Sweden)

Yuki Furuse

2015-11-01

Full Text Available Infection due to the Middle East respiratory syndrome coronavirus (MERS-CoV is widespread. The present study was performed to assess the protocols used for the molecular diagnosis of MERS-CoV by analyzing the nucleotide sequences of viruses detected between 2012 and 2015, including sequences from the large outbreak in eastern Asia in 2015. Although the diagnostic protocols were established only 2 years ago, mismatches between the sequences of primers/probes and viruses were found for several of the assays. Such mismatches could lead to a lower sensitivity of the assay, thereby leading to false-negative diagnosis. A slight modification in the primer design is suggested. Protocols for the molecular diagnosis of viral infections should be reviewed regularly after they are established, particularly for viruses that pose a great threat to public health such as MERS-CoV.

Chameleon sequences in neurodegenerative diseases.

Science.gov (United States)

Bahramali, Golnaz; Goliaei, Bahram; Minuchehr, Zarrin; Salari, Ali

2016-03-25

Chameleon sequences can adopt either alpha helix sheet or a coil conformation. Defining chameleon sequences in PDB (Protein Data Bank) may yield to an insight on defining peptides and proteins responsible in neurodegeneration. In this research, we benefitted from the large PDB and performed a sequence analysis on Chameleons, where we developed an algorithm to extract peptide segments with identical sequences, but different structures. In order to find new chameleon sequences, we extracted a set of 8315 non-redundant protein sequences from the PDB with an identity less than 25%. Our data was classified to "helix to strand (HE)", "helix to coil (HC)" and "strand to coil (CE)" alterations. We also analyzed the occurrence of singlet and doublet amino acids and the solvent accessibility in the chameleon sequences; we then sorted out the proteins with the most number of chameleon sequences and named them Chameleon Flexible Proteins (CFPs) in our dataset. Our data revealed that Gly, Val, Ile, Tyr and Phe, are the major amino acids in Chameleons. We also found that there are proteins such as Insulin Degrading Enzyme IDE and GTP-binding nuclear protein Ran (RAN) with the most number of chameleons (640 and 405 respectively). These proteins have known roles in neurodegenerative diseases. Therefore it can be inferred that other CFP's can serve as key proteins in neurodegeneration, and a study on them can shed light on curing and preventing neurodegenerative diseases. Copyright © 2016 Elsevier Inc. All rights reserved.

Chameleon sequences in neurodegenerative diseases

International Nuclear Information System (INIS)

Bahramali, Golnaz; Goliaei, Bahram; Minuchehr, Zarrin; Salari, Ali

2016-01-01

Chameleon sequences can adopt either alpha helix sheet or a coil conformation. Defining chameleon sequences in PDB (Protein Data Bank) may yield to an insight on defining peptides and proteins responsible in neurodegeneration. In this research, we benefitted from the large PDB and performed a sequence analysis on Chameleons, where we developed an algorithm to extract peptide segments with identical sequences, but different structures. In order to find new chameleon sequences, we extracted a set of 8315 non-redundant protein sequences from the PDB with an identity less than 25%. Our data was classified to “helix to strand (HE)”, “helix to coil (HC)” and “strand to coil (CE)” alterations. We also analyzed the occurrence of singlet and doublet amino acids and the solvent accessibility in the chameleon sequences; we then sorted out the proteins with the most number of chameleon sequences and named them Chameleon Flexible Proteins (CFPs) in our dataset. Our data revealed that Gly, Val, Ile, Tyr and Phe, are the major amino acids in Chameleons. We also found that there are proteins such as Insulin Degrading Enzyme IDE and GTP-binding nuclear protein Ran (RAN) with the most number of chameleons (640 and 405 respectively). These proteins have known roles in neurodegenerative diseases. Therefore it can be inferred that other CFP's can serve as key proteins in neurodegeneration, and a study on them can shed light on curing and preventing neurodegenerative diseases.

Chameleon sequences in neurodegenerative diseases

Energy Technology Data Exchange (ETDEWEB)

Bahramali, Golnaz [Institute of Biochemistry and Biophysics, University of Tehran, Tehran (Iran, Islamic Republic of); Goliaei, Bahram, E-mail: goliaei@ut.ac.ir [Institute of Biochemistry and Biophysics, University of Tehran, Tehran (Iran, Islamic Republic of); Minuchehr, Zarrin, E-mail: minuchehr@nigeb.ac.ir [Department of Systems Biotechnology, National Institute of Genetic Engineering and Biotechnology, (NIGEB), Tehran (Iran, Islamic Republic of); Salari, Ali [Department of Systems Biotechnology, National Institute of Genetic Engineering and Biotechnology, (NIGEB), Tehran (Iran, Islamic Republic of)

2016-03-25

Chameleon sequences can adopt either alpha helix sheet or a coil conformation. Defining chameleon sequences in PDB (Protein Data Bank) may yield to an insight on defining peptides and proteins responsible in neurodegeneration. In this research, we benefitted from the large PDB and performed a sequence analysis on Chameleons, where we developed an algorithm to extract peptide segments with identical sequences, but different structures. In order to find new chameleon sequences, we extracted a set of 8315 non-redundant protein sequences from the PDB with an identity less than 25%. Our data was classified to “helix to strand (HE)”, “helix to coil (HC)” and “strand to coil (CE)” alterations. We also analyzed the occurrence of singlet and doublet amino acids and the solvent accessibility in the chameleon sequences; we then sorted out the proteins with the most number of chameleon sequences and named them Chameleon Flexible Proteins (CFPs) in our dataset. Our data revealed that Gly, Val, Ile, Tyr and Phe, are the major amino acids in Chameleons. We also found that there are proteins such as Insulin Degrading Enzyme IDE and GTP-binding nuclear protein Ran (RAN) with the most number of chameleons (640 and 405 respectively). These proteins have known roles in neurodegenerative diseases. Therefore it can be inferred that other CFP's can serve as key proteins in neurodegeneration, and a study on them can shed light on curing and preventing neurodegenerative diseases.

Imaging diagnosis of bronchial asthma and related diseases

International Nuclear Information System (INIS)

Sakai, Fumikazu; Fujimura, Mikihiko; Kimura, Fumiko; Fujimura, Kaori; Hayano, Toshio; Nishii, Noriko; Machida, Haruhiko; Toda, Jo; Saito, Naoko

2002-01-01

We describe imaging features of bronchial asthma and related diseases. The practical roles of imaging diagnosis are the evaluation of severity and complications of bronchial asthma and differential diagnosis of diseases showing asthmatic symptoms other than bronchial asthma. (author)

Towards clinical molecular diagnosis of inherited cardiac conditions: a comparison of bench-top genome DNA sequencers.

Directory of Open Access Journals (Sweden)

Xinzhong Li

Full Text Available Molecular genetic testing is recommended for diagnosis of inherited cardiac disease, to guide prognosis and treatment, but access is often limited by cost and availability. Recently introduced high-throughput bench-top DNA sequencing platforms have the potential to overcome these limitations.We evaluated two next-generation sequencing (NGS platforms for molecular diagnostics. The protein-coding regions of six genes associated with inherited arrhythmia syndromes were amplified from 15 human samples using parallelised multiplex PCR (Access Array, Fluidigm, and sequenced on the MiSeq (Illumina and Ion Torrent PGM (Life Technologies. Overall, 97.9% of the target was sequenced adequately for variant calling on the MiSeq, and 96.8% on the Ion Torrent PGM. Regions missed tended to be of high GC-content, and most were problematic for both platforms. Variant calling was assessed using 107 variants detected using Sanger sequencing: within adequately sequenced regions, variant calling on both platforms was highly accurate (Sensitivity: MiSeq 100%, PGM 99.1%. Positive predictive value: MiSeq 95.9%, PGM 95.5%. At the time of the study the Ion Torrent PGM had a lower capital cost and individual runs were cheaper and faster. The MiSeq had a higher capacity (requiring fewer runs, with reduced hands-on time and simpler laboratory workflows. Both provide significant cost and time savings over conventional methods, even allowing for adjunct Sanger sequencing to validate findings and sequence exons missed by NGS.MiSeq and Ion Torrent PGM both provide accurate variant detection as part of a PCR-based molecular diagnostic workflow, and provide alternative platforms for molecular diagnosis of inherited cardiac conditions. Though there were performance differences at this throughput, platforms differed primarily in terms of cost, scalability, protocol stability and ease of use. Compared with current molecular genetic diagnostic tests for inherited cardiac arrhythmias

Radiological diagnosis in AIDS - associated diseases: survey and differential diagnosis

International Nuclear Information System (INIS)

Rademaker, J.; Frahm, C.

1997-01-01

Acute manifestations of illnesses in patients with HIV-infection or AIDS will benefit from rapid diagnosis. Radiologic examinations provide substantial information to narrow the differential diagnosis. This article reviews clinically important HIV-associated diseases for the radiologist. The braod spectrum of possible manifestations is illustrated by the accompanying case reports that typify the complexity of diagnoses in this growing problem worldwide. (orig.) [de

Whole Exome Sequencing for the differential diagnosis of primary adrenal insufficiency in children

Directory of Open Access Journals (Sweden)

Li F Chan

2015-08-01

Full Text Available Adrenal insufficiency is a rare, but potentially fatal medical condition. In children the cause is most commonly congenital and in recent years a growing number of causative gene mutations have been identified resulting in a myriad of syndromes that share adrenal insufficiency as one of the main characteristics. The evolution of adrenal insufficiency is dependent on the variant and the particular gene affected, meaning rapid and accurate diagnosis is imperative for effective treatment of the patient. Common practice is for candidate genes to be sequenced individually, which is a time consuming process and complicated by overlapping clinical phenotypes. However, with the availability, and increasing cost effectiveness of whole exome sequencing there is the potential for this to become a powerful diagnostic tool. Here we report the results of whole exome sequencing of 43 patients referred to us with a diagnosis of familial glucocorticoid deficiency (FGD who were mutation negative for MC2R, MRAP and STAR the most commonly mutated genes in FGD. WES provided a rapid genetic diagnosis in 17/43 sequenced patients, for the remaining 60% the gene defect may be within intronic/regulatory regions not covered by WES or may be in gene(s representing novel aetiologies. The diagnosis of isolated or familial glucocorticoid deficiency was only confirmed in 3 of the 17 patients, other genetic diagnoses were adrenal hypo- and hyperplasia, Triple A and autoimmune polyendocrinopathy syndrome type I, emphasizing both the difficulty of phenotypically distinguishing between disorders of PAI and the utility of WES as a tool to achieve this.

LORD: a phenotype-genotype semantically integrated biomedical data tool to support rare disease diagnosis coding in health information systems.

Science.gov (United States)

Choquet, Remy; Maaroufi, Meriem; Fonjallaz, Yannick; de Carrara, Albane; Vandenbussche, Pierre-Yves; Dhombres, Ferdinand; Landais, Paul

Characterizing a rare disease diagnosis for a given patient is often made through expert's networks. It is a complex task that could evolve over time depending on the natural history of the disease and the evolution of the scientific knowledge. Most rare diseases have genetic causes and recent improvements of sequencing techniques contribute to the discovery of many new diseases every year. Diagnosis coding in the rare disease field requires data from multiple knowledge bases to be aggregated in order to offer the clinician a global information space from possible diagnosis to clinical signs (phenotypes) and known genetic mutations (genotype). Nowadays, the major barrier to the coding activity is the lack of consolidation of such information scattered in different thesaurus such as Orphanet, OMIM or HPO. The Linking Open data for Rare Diseases (LORD) web portal we developed stands as the first attempt to fill this gap by offering an integrated view of 8,400 rare diseases linked to more than 14,500 signs and 3,270 genes. The application provides a browsing feature to navigate through the relationships between diseases, signs and genes, and some Application Programming Interfaces to help its integration in health information systems in routine.

Prenatal Diagnosis Of Tay-Sachs Disease

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Özgür Özyüncü

2010-04-01

CONCLUSION: Tay-Sachs disease can be diagnosed prenatally by measuring hexosaminidase enzyme activity in fetal tissue samples with an acceptable complication rate. Prenatal diagnosis should be offered to families who have affected siblings with Tay-Sachs disease.

Tickborne infectious diseases: diagnosis and management

National Research Council Canada - National Science Library

Cunha, Burke A

2000-01-01

... to particular flora and fauna. The purpose of Tickborne Infectious Diseases: Diagnosis and Management is to condense in a single book different approaches and paradigms of tickborne infectious diseases. Three chapters are devoted to background information, including the natural history of ticks, the diagnostic procedures of tickborne diseases, and the new tick-transm...

Leveraging Collaborative Filtering to Accelerate Rare Disease Diagnosis.

Science.gov (United States)

Shen, Feichen; Liu, Sijia; Wang, Yanshan; Wang, Liwei; Afzal, Naveed; Liu, Hongfang

2017-01-01

In the USA, rare diseases are defined as those affecting fewer than 200,000 patients at any given time. Patients with rare diseases are frequently misdiagnosed or undiagnosed which may due to the lack of knowledge and experience of care providers. We hypothesize that patients' phenotypic information available in electronic medical records (EMR) can be leveraged to accelerate disease diagnosis based on the intuition that providers need to document associated phenotypic information to support the diagnosis decision, especially for rare diseases. In this study, we proposed a collaborative filtering system enriched with natural language processing and semantic techniques to assist rare disease diagnosis based on phenotypic characterization. Specifically, we leveraged four similarity measurements with two neighborhood algorithms on 2010-2015 Mayo Clinic unstructured large patient cohort and evaluated different approaches. Preliminary results demonstrated that the use of collaborative filtering with phenotypic information is able to stratify patients with relatively similar rare diseases.

Prenatal Diagnosis of a Case of Norrie Disease with Late Development of Bilateral Ocular Malformation.

Science.gov (United States)

Wu, Li Hong; Chen, Li-Hong; Xie, Hongning; Xie, Ying-Jun

2017-06-01

We report a case of Norrie disease, diagnosed by prenatal ultrasound, confirmed by Sanger sequencing of the DNP gene from the aborted fetal cord blood and histologically. Prenatal ultrasound revealed no abnormality in either eye at 22 +1 and 31 +4 gestational weeks, but at 36 +5 gestational weeks both eyes had massive vitreous cavity opacities with complete retinal detachment. Norrie disease was initially suspected because of an older male sibling with the disease. To our knowledge, prenatal ultrasound diagnosis of Norrie disease has been previously described only one case in 1993 in a 34-week-old fetus. The normal eye development until after 31 + 4 gestational weeks provides insight into the first manifestation and then the rapid progression of the eye disease.

Use of functional tests in radioimmune diagnosis of endocrine diseases

International Nuclear Information System (INIS)

Slavnov, V.N.

1988-01-01

Radioimmunoassay for determining corticotropin (ACTH), somatotropin (STH), prolactin (LTH) and thyrotropin (TTH) concentration in blood for endocrine disease diagnosis are described. Reactions of earlier mentioned functional tests to specific stimulators and inhibitors for differential diagnosis of such diseases as Icenko-Cushing one, pituitary body and hypothalamus diseases, galactorrhea and amenorrhea syndrome are considered. The diagnosis reliability is underlined

Biomarker detection for disease diagnosis using cost-effective microfluidic platforms.

Science.gov (United States)

Sanjay, Sharma T; Fu, Guanglei; Dou, Maowei; Xu, Feng; Liu, Rutao; Qi, Hao; Li, XiuJun

2015-11-07

Early and timely detection of disease biomarkers can prevent the spread of infectious diseases, and drastically decrease the death rate of people suffering from different diseases such as cancer and infectious diseases. Because conventional diagnostic methods have limited application in low-resource settings due to the use of bulky and expensive instrumentation, simple and low-cost point-of-care diagnostic devices for timely and early biomarker diagnosis is the need of the hour, especially in rural areas and developing nations. The microfluidics technology possesses remarkable features for simple, low-cost, and rapid disease diagnosis. There have been significant advances in the development of microfluidic platforms for biomarker detection of diseases. This article reviews recent advances in biomarker detection using cost-effective microfluidic devices for disease diagnosis, with the emphasis on infectious disease and cancer diagnosis in low-resource settings. This review first introduces different microfluidic platforms (e.g. polymer and paper-based microfluidics) used for disease diagnosis, with a brief description of their common fabrication techniques. Then, it highlights various detection strategies for disease biomarker detection using microfluidic platforms, including colorimetric, fluorescence, chemiluminescence, electrochemiluminescence (ECL), and electrochemical detection. Finally, it discusses the current limitations of microfluidic devices for disease biomarker detection and future prospects.

MR Cholangiography: Axial TSE-T2 Sequence Evaluation in the Diagnosis of Choledocholithiasis

International Nuclear Information System (INIS)

Alustiza, J. M.; Gervas, C.; Garcia, E.; Recondo, J. A.

2003-01-01

To evaluate diagnostic precision of the axial TSE-T2 sequence in the diagnosis of choledocholithiasis. Retrospective analysis of all those MR cholangiography studies performed in our center between January 1998 and June 1999 which were later subjected to conventional cholangiography (intraoperative) as a golden standard. A total of 39 patients was studied. Imaging parameters of the sequence evaluated, fat-suppressed TSE-T2 in the axial plane, were as follows: TE 100 ms, TR 1.800 ms, turbo factor 23 FOV 375 mm, NSA 4, 228 x 256 matrix, respiratory compensation, number of slices 35, slice thickness 3 mm, contiguous slices, scan duration 5'4''. Without having been informed as to the cholangiography result, two radiologists independently analyzed this sequence in order to determine the presence of choledocholithiasis. Their results were latter compared with those of the conventional cholangiography. The sensitivity, specificity and agreement between results were all calculated. 21 patients had choledocholithiasis. The analyzed sequence presented sensitivity 81%, specificity 89%, and agreement between radiologists 98%, Kappa index 0.949. The axial sequence TSE-T2 is reliable for choledocholithiasis diagnosis. (Author) 9 refs

Exome sequencing of index patients with retinal dystrophies as a tool for molecular diagnosis.

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Marta Corton

Full Text Available Retinal dystrophies (RD are a group of hereditary diseases that lead to debilitating visual impairment and are usually transmitted as a Mendelian trait. Pathogenic mutations can occur in any of the 100 or more disease genes identified so far, making molecular diagnosis a rather laborious process. In this work we explored the use of whole exome sequencing (WES as a tool for identification of RD mutations, with the aim of assessing its applicability in a diagnostic context.We ascertained 12 Spanish families with seemingly recessive RD. All of the index patients underwent mutational pre-screening by chip-based sequence hybridization and resulted to be negative for known RD mutations. With the exception of one pedigree, to simulate a standard diagnostic scenario we processed by WES only the DNA from the index patient of each family, followed by in silico data analysis. We successfully identified causative mutations in patients from 10 different families, which were later verified by Sanger sequencing and co-segregation analyses. Specifically, we detected pathogenic DNA variants (∼50% novel mutations in the genes RP1, USH2A, CNGB3, NMNAT1, CHM, and ABCA4, responsible for retinitis pigmentosa, Usher syndrome, achromatopsia, Leber congenital amaurosis, choroideremia, or recessive Stargardt/cone-rod dystrophy cases.Despite the absence of genetic information from other family members that could help excluding nonpathogenic DNA variants, we could detect causative mutations in a variety of genes known to represent a wide spectrum of clinical phenotypes in 83% of the patients analyzed. Considering the constant drop in costs for human exome sequencing and the relative simplicity of the analyses made, this technique could represent a valuable tool for molecular diagnostics or genetic research, even in cases for which no genotypes from family members are available.

Molecular genetic mutation analysis in Menkes-disease with prenatal diagnosis

DEFF Research Database (Denmark)

László, Aranka; Endreffy, Emoke; Tümer, Zeynep

2010-01-01

Menkes disease (MD) is an X-linked recessive multisystemic lethal, heredodegenerative disorder. Progressive neurodegeneration and connective tissue disturbances with microscopically kinky hair are the main symptoms. Molecular genetic mutation analysis was made at a Hungarian male infant suffering...... from MD and prenatal diagnosis was done in this MD loaded family. METHOD: The 12th exon of ATP7A gene has been analyzed by dideoxy-finger printing (DDF), polymerase chain reaction (PCR), direct sequencing of exon 12. The specific mutation was screened from chorionic villi of the maternal aunt at the 14......th gestational week. RESULTS: In the exon 12th a basic pair substitution with Arg 844 His change was detected leading to very severe fatal missense mutation....

Ultrasonographyin diagnosis of thoracic diseases

OpenAIRE

Stević Ruža; Jaković Radoslav; Mašulović Dragan; Nagorni-Obradović Ljudmila; Mujović Nataša; Jovanović Dragana

2010-01-01

Introduction. Chest sonography was used until recently mainly for diagnosis of pleural diseases. High resolution ultrasound machines enable ultrasound application not only in pleural diseases detection, but in diagnosing peripheral lung and mediastinal lesions. Ultrasonography can define the origin and structure of the lesion of thoracic wall, pleural and peripheral lung lesions and mediastinal lesions. Pleural lesions. Ultrasonography is very useful in diagnosing pleural effusion and disting...

Same-day genomic and epigenomic diagnosis of brain tumors using real-time nanopore sequencing.

Science.gov (United States)

Euskirchen, Philipp; Bielle, Franck; Labreche, Karim; Kloosterman, Wigard P; Rosenberg, Shai; Daniau, Mailys; Schmitt, Charlotte; Masliah-Planchon, Julien; Bourdeaut, Franck; Dehais, Caroline; Marie, Yannick; Delattre, Jean-Yves; Idbaih, Ahmed

2017-11-01

Molecular classification of cancer has entered clinical routine to inform diagnosis, prognosis, and treatment decisions. At the same time, new tumor entities have been identified that cannot be defined histologically. For central nervous system tumors, the current World Health Organization classification explicitly demands molecular testing, e.g., for 1p/19q-codeletion or IDH mutations, to make an integrated histomolecular diagnosis. However, a plethora of sophisticated technologies is currently needed to assess different genomic and epigenomic alterations and turnaround times are in the range of weeks, which makes standardized and widespread implementation difficult and hinders timely decision making. Here, we explored the potential of a pocket-size nanopore sequencing device for multimodal and rapid molecular diagnostics of cancer. Low-pass whole genome sequencing was used to simultaneously generate copy number (CN) and methylation profiles from native tumor DNA in the same sequencing run. Single nucleotide variants in IDH1, IDH2, TP53, H3F3A, and the TERT promoter region were identified using deep amplicon sequencing. Nanopore sequencing yielded ~0.1X genome coverage within 6 h and resulting CN and epigenetic profiles correlated well with matched microarray data. Diagnostically relevant alterations, such as 1p/19q codeletion, and focal amplifications could be recapitulated. Using ad hoc random forests, we could perform supervised pan-cancer classification to distinguish gliomas, medulloblastomas, and brain metastases of different primary sites. Single nucleotide variants in IDH1, IDH2, and H3F3A were identified using deep amplicon sequencing within minutes of sequencing. Detection of TP53 and TERT promoter mutations shows that sequencing of entire genes and GC-rich regions is feasible. Nanopore sequencing allows same-day detection of structural variants, point mutations, and methylation profiling using a single device with negligible capital cost. It

Whole-genome and Transcriptome Sequencing of Prostate Cancer Identify New Genetic Alterations Driving Disease Progression

DEFF Research Database (Denmark)

Ren, Shancheng; Wei, Gong-Hong; Liu, Dongbing

2018-01-01

BACKGROUND: Global disparities in prostate cancer (PCa) incidence highlight the urgent need to identify genomic abnormalities in prostate tumors in different ethnic populations including Asian men. OBJECTIVE: To systematically explore the genomic complexity and define disease-driven genetic......-scale and comprehensive genomic data of prostate cancer from Asian population. Identification of these genetic alterations may help advance prostate cancer diagnosis, prognosis, and treatment....... alterations in PCa. DESIGN, SETTING, AND PARTICIPANTS: The study sequenced whole-genome and transcriptome of tumor-benign paired tissues from 65 treatment-naive Chinese PCa patients. Subsequent targeted deep sequencing of 293 PCa-relevant genes was performed in another cohort of 145 prostate tumors. OUTCOME...

Early diagnosis of Alzheimer's disease. Clinical significance and future perspectives

International Nuclear Information System (INIS)

Buerger, K.; Teipel, S.J.; Hampel, H.

2000-01-01

Early diagnosis of Alzheimer's disease describes the recognition and diagnosis in patients with very mild dementia. Internationally accepted diagnostic criteria support the diagnosis based on clinical evaluation. Recent advances in structural and functional neuroimaging as well as studies on specific proteins in the cerebro-spinal fluid that are related to distinct pathophysiological disease processes are most promising approaches to defining biological markers of Alzheimer's disease. (orig.) [de

Lyme disease: clinical diagnosis and treatment

Science.gov (United States)

Hatchette, TF; Davis, I; Johnston, BL

2014-01-01

Background Lyme disease is an emerging zoonotic infection in Canada. As the Ixodes tick expands its range, more Canadians will be exposed to Borrelia burgdorferi, the bacterium that causes Lyme disease. Objective To review the clinical diagnosis and treatment of Lyme disease for front-line clinicians. Methods A literature search using PubMed and restricted to articles published in English between 1977 and 2014. Results Individuals in Lyme-endemic areas are at greatest risk, but not all tick bites transmit Lyme disease. The diagnosis is predominantly clinical. Patients with Lyme disease may present with early disease that is characterized by a “bull’s eye rash”, fever and myalgias or with early disseminated disease that can manifest with arthralgias, cardiac conduction abnormalities or neurologic symptoms. Late Lyme disease in North America typically manifests with oligoarticular arthritis but can present with a subacute encephalopathy. Antibiotic treatment is effective against Lyme disease and works best when given early in the infection. Prophylaxis with doxycyline may be indicated in certain circumstances. While a minority of patients may have persistent symptoms, evidence does not demonstrate that prolonged courses of antibiotics improve outcome. Conclusion Clinicians need to be aware of the signs and symptoms of Lyme disease. Knowing the regions where Borrelia infection is endemic in North America is important for recognizing patients at risk and informing the need for treatment. PMID:29769842

[Diagnosis and treatment of Pompe disease].

Science.gov (United States)

Bravo-Oro, Antonio; de la Fuente-Cortez, Beatriz; Molina-García, Avril; Romero-Díaz, Víktor; Rodríguez-Leyva, Ildefonso; Esmer-Sánchez, María del Carmen

2013-01-01

Pompe disease is a rare, progressive and often fatal neuromuscular disorder. It is caused by a deficiency of the lysosomal alpha-glucosidase. Among glycogen storage disorders, it is one of the most common. Its clinical manifestations can start at any moment of life, with a very variable symptomatology. In this article, we show an extended revision of the literature in regards to the main medical aspects of Pompe disease: etiology, psychopathology, epidemiology, clinical variants, pathological diagnosis, and enzyme replacement therapy. With this information, we created a diagnostic and therapeutic guide, which is addressed to specialists and to first-level physicians, in order to let them identify both the classic and the late forms of this disease. We describe as well the best, timely, multidisciplinary treatment in use. Also, we show some suggestions to the proper functioning of health institutions, and routes to diagnosis. We conclude that Pompe disease may be properly diagnosed and treated if health care professionals follow the internationally approved recommendations.

CT diagnosis in diseases of the breast

International Nuclear Information System (INIS)

Han Hongbin; Xie Jingxia

1998-01-01

Purpose: To study the CT signs of breast diseases, and discuss the value of CT in the diagnosis of breast cancer and the axillary lymph node (LN) metastases. Materials and methods: Fifty three cases were reported, including breast cancer 30 cases and benign diseases 23 cases. CT were performed in all patients, 44 also had mammography examination. Results: (1) The CT appearance of breast cancer: round or irregular mass, spiculate border, duct retraction, involved Cooper's ligament, deformed adipose space etc. Benign hyperplasia: Irregular mass and symmetrical thickening of breast glands. Cystic hyperplasia: typically multiple, round, liquid-density mass. (2) CT was comparable to mammography in terms of differential diagnosis, however with breast mass located near the axilla or for evaluation of the thoracic wall. CT was superior to mammography. CT was also helpful in detecting LN metastases. Conclusion: CT is valuable in detecting and differentiating breast diseases as well as in the diagnosis of LN metastases

Whole Genome Sequencing Increases Molecular Diagnostic Yield Compared with Current Diagnostic Testing for Inherited Retinal Disease.

Science.gov (United States)

Ellingford, Jamie M; Barton, Stephanie; Bhaskar, Sanjeev; Williams, Simon G; Sergouniotis, Panagiotis I; O'Sullivan, James; Lamb, Janine A; Perveen, Rahat; Hall, Georgina; Newman, William G; Bishop, Paul N; Roberts, Stephen A; Leach, Rick; Tearle, Rick; Bayliss, Stuart; Ramsden, Simon C; Nemeth, Andrea H; Black, Graeme C M

2016-05-01

To compare the efficacy of whole genome sequencing (WGS) with targeted next-generation sequencing (NGS) in the diagnosis of inherited retinal disease (IRD). Case series. A total of 562 patients diagnosed with IRD. We performed a direct comparative analysis of current molecular diagnostics with WGS. We retrospectively reviewed the findings from a diagnostic NGS DNA test for 562 patients with IRD. A subset of 46 of 562 patients (encompassing potential clinical outcomes of diagnostic analysis) also underwent WGS, and we compared mutation detection rates and molecular diagnostic yields. In addition, we compared the sensitivity and specificity of the 2 techniques to identify known single nucleotide variants (SNVs) using 6 control samples with publically available genotype data. Diagnostic yield of genomic testing. Across known disease-causing genes, targeted NGS and WGS achieved similar levels of sensitivity and specificity for SNV detection. However, WGS also identified 14 clinically relevant genetic variants through WGS that had not been identified by NGS diagnostic testing for the 46 individuals with IRD. These variants included large deletions and variants in noncoding regions of the genome. Identification of these variants confirmed a molecular diagnosis of IRD for 11 of the 33 individuals referred for WGS who had not obtained a molecular diagnosis through targeted NGS testing. Weighted estimates, accounting for population structure, suggest that WGS methods could result in an overall 29% (95% confidence interval, 15-45) uplift in diagnostic yield. We show that WGS methods can detect disease-causing genetic variants missed by current NGS diagnostic methodologies for IRD and thereby demonstrate the clinical utility and additional value of WGS. Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Diagnosis and treatment of gastroesophageal reflux disease

Science.gov (United States)

Badillo, Raul; Francis, Dawn

2014-01-01

Gastroesophageal reflux disease (GERD) is a common disease with a prevalence as high as 10%-20% in the western world. The disease can manifest in various symptoms which can be grouped into typical, atypical and extra-esophageal symptoms. Those with the highest specificity for GERD are acid regurgitation and heartburn. In the absence of alarm symptoms, these symptoms can allow one to make a presumptive diagnosis and initiate empiric therapy. In certain situations, further diagnostic testing is needed to confirm the diagnosis as well as to assess for complications or alternate causes for the symptoms. GERD complications include erosive esophagitis, peptic stricture, Barrett’s esophagus, esophageal adenocarcinoma and pulmonary disease. Management of GERD may involve lifestyle modification, medical therapy and surgical therapy. Lifestyle modifications including weight loss and/or head of bed elevation have been shown to improve esophageal pH and/or GERD symptoms. Medical therapy involves acid suppression which can be achieved with antacids, histamine-receptor antagonists or proton-pump inhibitors. Whereas most patients can be effectively managed with medical therapy, others may go on to require anti-reflux surgery after undergoing a proper pre-operative evaluation. The purpose of this review is to discuss the current approach to the diagnosis and treatment of gastroesophageal reflux disease. PMID:25133039

MRI manifestation for the diagnosis of sporadic Creutzfeldt-Jakob disease

International Nuclear Information System (INIS)

Xue Yonggang; Qi Ji; Xia Shuang

2007-01-01

Objective: To study the MRI features of sporadic Creutzfeldt-Jakob disease (sCJD). Methods: Three patients with clinically diagnosed sCJD underwent MR study, including SE T 1 WI, FSE T 2 WI, and DWI sequences. The MR imaging features were analyzed. Results: The lesions were not definite either in SE T 1 WI or in FSE T 2 WI, but were prominent in DWI. Abnormal hyperintensive signal appeared in the cerebral cortex, with the frontal, parietal, and occipital lobes being the mostly involved region. The subcortical white matter was normal. The bilateral caudate nuclei and thalami could also be involved. The abnormal signal could be either symmetrical or asymmetrical. There was diffuse atrophy of the brain parenchyma in the late phase of disease, especially in the cortex. Conclusion: With the application of MR study, especially the DWI, combined with its characteristic clinical manifestation, the diagnosis of sCJD can be made definitely. (authors)

Value of Cine-MRI sequences before and after injection in the diagnosis of acute myocarditis.

Science.gov (United States)

Zidi, Asma; Zairi, Ihsen; Mzoughi, Khadija; Zakhama, Lilia; Kamoun, Ikram; Ben Halima, Afef; Ridene, Imen

2016-11-01

Cardiovascular magnetic resonance (CMR) has become the examination of choice in case of suspicion of acute myocarditis. Late gadolinium enhancement (LGE) imaging is very important to establish this diagnosis. Cine MRI sequences are useful for the study of the myocardial contractility.   The purpose is to estimate the value of cine MRI sequences before and after injection for the diagnosis of acute myocarditis compared with late gadolinium enhanced sequences. We prospectively included 40 patients having a high suspicion of acute myocarditis and examined using a 1.5 Tesla CMR. Cine MRI sequences before and after injection were performed. The protocol also include  T2-weighted  short- tau-inversion-recovery (STIR T2) fast spin echo MRI and LGE imaging eight minutes after injection with visual adjustment of inversion time. Delayed enhancement was found among 23 patients. Fifteen patients (65 %) presented a spontaneous hyper signal detected visually on Cine MRI sequences before injection and 11 patients (48 %) on STIR T2. The hyper signal on Cine MRI sequences after injection of gadolinium was the same topography that the late raising at 23 patients. In addition, we highlighted a significant difference between this hyper signal before injection and the left ventricle ejection fraction (p=0.022) as well as with the telesystolic volume of the left ventricle (LV) indexed by the body mass (p=0.039). Our study suggests that Cine MRI sequences after injection are of equal performance in the diagnosis of acute myocarditis as the LGE sequences and its contibution is important when we want to shorten the examination or when inversion time isn't optimal.

Morbidity in early Parkinson's disease and prior to diagnosis

DEFF Research Database (Denmark)

Frandsen, Rune; Kjellberg, Jakob; Ibsen, Rikke

2014-01-01

BACKGROUND: Nonmotor symptoms are probably present prior to, early on, and following, a diagnosis of Parkinson's disease. Nonmotor symptoms may hold important information about the progression of Parkinson's disease. OBJECTIVE: To evaluated the total early and prediagnostic morbidities in the 3......, poisoning and certain other external causes, and other factors influencing health status and contact with health services. It was negatively associated with neoplasm, cardiovascular, and respiratory diseases. CONCLUSIONS: Patients with a diagnosis of Parkinson's disease present significant differences...

Diagnosis and treatment of invasive fungal diseases in patients with severe liver diseases

Directory of Open Access Journals (Sweden)

ZANG Hong

2016-09-01

Full Text Available Invasive fungal diseases (IFDs are an important factor affecting the prognosis of patients with severe liver diseases, and their early diagnosis remains a challenge for clinicians. The four most commonly seen IFDs are candidiasis, aspergillosis, cryptococcosis, and pneumocystis pneumonia. We should pay attention to the risk of developing IFDs in patients with severe liver diseases during clinical management. Particularly, early diagnosis and proper treatment of IFDs are important in high-risk patients. These are vital to improving the prognosis of patients with severe liver diseases.

Next Generation Sequencing Methods for Diagnosis of Epilepsy Syndromes

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Paul Dunn

2018-02-01

Full Text Available Epilepsy is a neurological disorder characterized by an increased predisposition for seizures. Although this definition suggests that it is a single disorder, epilepsy encompasses a group of disorders with diverse aetiologies and outcomes. A genetic basis for epilepsy syndromes has been postulated for several decades, with several mutations in specific genes identified that have increased our understanding of the genetic influence on epilepsies. With 70-80% of epilepsy cases identified to have a genetic cause, there are now hundreds of genes identified to be associated with epilepsy syndromes which can be analyzed using next generation sequencing (NGS techniques such as targeted gene panels, whole exome sequencing (WES and whole genome sequencing (WGS. For effective use of these methodologies, diagnostic laboratories and clinicians require information on the relevant workflows including analysis and sequencing depth to understand the specific clinical application and diagnostic capabilities of these gene sequencing techniques. As epilepsy is a complex disorder, the differences associated with each technique influence the ability to form a diagnosis along with an accurate detection of the genetic etiology of the disorder. In addition, for diagnostic testing, an important parameter is the cost-effectiveness and the specific diagnostic outcome of each technique. Here, we review these commonly used NGS techniques to determine their suitability for application to epilepsy genetic diagnostic testing.

Can Biomarkers Help the Early Diagnosis of Parkinson's Disease?

Institute of Scientific and Technical Information of China (English)

Weidong Le; Jie Dong; Song Li; Amos D.Korczyn

2017-01-01

Parkinson's disease (PD) is a complex neurodegenerative disease with progressive loss of dopamine neurons.PD patients usually manifest a series of motor and non-motor symptoms.In order to provide better early diagnosis and subsequent disease-modifying therapies for PD patients,there is an urgent need to identify sensitive and specific biomarkers.Biomarkers can be divided into four categories:clinical,imaging,biochemical,and genetic.Ideal biomarkers not only improve our understanding of PD pathogenesis and progression,but also provide benefits for early risk evaluation and clinical diagnosis of PD.Although many efforts have been made and several biomarkers have been extensively investigated,few if any have been found useful for early diagnosis.Here,we summarize recent developments in the discovered biomarkers of PD and discuss their merits and limitations for the early diagnosis of PD.

MRI diagnosis of eyeball diseases

International Nuclear Information System (INIS)

Tao Xiaofeng; Shi Zengru; Xiao Xiangsheng; Yu Hong; Wei Ruili

2003-01-01

Objective: To review the MR imaging of eyeball mass in 75 patients with the intention to enhance the acknowledgement to eyeball diseases. Methods: Seventy-five patients, 45 males and 30 females, were examined with MRI before treatment. Most MRI studies were performed with head coil and a few with orbit surface coil. Sagittal, coronal, and axial images were attained. Enhanced MRI studies were performed in 37 cases. High magnetic field MRI studies were performed with additional fat saturation technique. Results: Retinoblastoma (20 cases) showed isointensity in 11 and low signal intensity in 9 on T 1 WI, and isointensity in 5 and slight high signal in 15 on T 2 WI. Coats' disease (5 cases) involved single eyeball in all cases without calcification or eyeball enlargement, and presented as slight high signal on T 1 WI and high signal on T 2 WI. Choroidal angioma (3 cases) showed slight high signal on T 1 WI and high signal on T 2 WI. Metastasis (20 cases) was located in the posterior wall of the eyeball. Extra-global invasion occurred in 8 cases and intra-global invasion in 20. Marked thickening of the global wall with isointensity (8 cases) or low signal intensity (12 cases) was detected on T 1 WI, and isointensity (6 cases) or slight high signal intensity (14 cases) was demonstrated on T 2 WI. Marked enhancement was revealed in all 15 cases. Melanoma (7 cases) showed high signal intensity (5) and isointensity (2) on T 1 WI, and low signal (7) on T 2 WI. Retinal detachment (19 cases) showed high signal on both T 1 and T 2 WI, etc. In the diagnosis of eyeball diseases with MRI, the total sensitivity was 100% and specificity was 86.7%. Conclusions: MRI imaging is an important examination method to eyeball diseases, and most diagnosis and differential diagnosis of eyeball diseases can be made correctly with MRI

X-ray diagnosis of retropatellar diseases

International Nuclear Information System (INIS)

Wahlers, B.

1979-01-01

The article reports on a comprehensive, stepwise diagnosis in diseases of the knee joints. This includes a description of the indication, the technique of taking X-ray films, and X-ray findings, as well as arthrography of the femoropatellar joint in retropatellar diseases such as chondropathia patellae, osteochondrosis dissecans, traumas of the knee joints and arthrosis deformans. (orig.) [de

Diagnosis of Fanconi Anemia: Mutation Analysis by Multiplex Ligation-Dependent Probe Amplification and PCR-Based Sanger Sequencing

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Johan J. P. Gille

2012-01-01

Full Text Available Fanconi anemia (FA is a rare inherited disease characterized by developmental defects, short stature, bone marrow failure, and a high risk of malignancies. FA is heterogeneous: 15 genetic subtypes have been distinguished so far. A clinical diagnosis of FA needs to be confirmed by testing cells for sensitivity to cross-linking agents in a chromosomal breakage test. As a second step, DNA testing can be employed to elucidate the genetic subtype of the patient and to identify the familial mutations. This knowledge allows preimplantation genetic diagnosis (PGD and enables prenatal DNA testing in future pregnancies. Although simultaneous testing of all FA genes by next generation sequencing will be possible in the near future, this technique will not be available immediately for all laboratories. In addition, in populations with strong founder mutations, a limited test using Sanger sequencing and MLPA will be a cost-effective alternative. We describe a strategy and optimized conditions for the screening of FANCA, FANCB, FANCC, FANCE, FANCF, and FANCG and present the results obtained in a cohort of 54 patients referred to our diagnostic service since 2008. In addition, the follow up with respect to genetic counseling and carrier screening in the families is discussed.

Diagnosis of Fanconi Anemia: Mutation Analysis by Multiplex Ligation-Dependent Probe Amplification and PCR-Based Sanger Sequencing

Science.gov (United States)

Gille, Johan J. P.; Floor, Karijn; Kerkhoven, Lianne; Ameziane, Najim; Joenje, Hans; de Winter, Johan P.

2012-01-01

Fanconi anemia (FA) is a rare inherited disease characterized by developmental defects, short stature, bone marrow failure, and a high risk of malignancies. FA is heterogeneous: 15 genetic subtypes have been distinguished so far. A clinical diagnosis of FA needs to be confirmed by testing cells for sensitivity to cross-linking agents in a chromosomal breakage test. As a second step, DNA testing can be employed to elucidate the genetic subtype of the patient and to identify the familial mutations. This knowledge allows preimplantation genetic diagnosis (PGD) and enables prenatal DNA testing in future pregnancies. Although simultaneous testing of all FA genes by next generation sequencing will be possible in the near future, this technique will not be available immediately for all laboratories. In addition, in populations with strong founder mutations, a limited test using Sanger sequencing and MLPA will be a cost-effective alternative. We describe a strategy and optimized conditions for the screening of FANCA, FANCB, FANCC, FANCE, FANCF, and FANCG and present the results obtained in a cohort of 54 patients referred to our diagnostic service since 2008. In addition, the follow up with respect to genetic counseling and carrier screening in the families is discussed. PMID:22778927

Incidence, disease phenotype at diagnosis, and early disease course in inflammatory bowel diseases in Western Hungary, 2002-2006.

Science.gov (United States)

Lakatos, Laszlo; Kiss, Lajos S; David, Gyula; Pandur, Tunde; Erdelyi, Zsuzsanna; Mester, Gabor; Balogh, Mihaly; Szipocs, Istvan; Molnar, Csaba; Komaromi, Erzsebet; Lakatos, Peter Laszlo

2011-12-01

Recent trends indicate a change in the epidemiology of inflammatory bowel diseases (IBD), with previously low incidence areas now reporting a progressive rise in the incidence. Our aim was to analyze the incidence and disease phenotype at diagnosis in IBD in the population-based Veszprem Province database, which included incident patients diagnosed between January 1, 2002 and December 31, 2006. Data of 393 incident patients were analyzed (ulcerative colitis [UC]: 220, age-at-diagnosis: 40.5 years; Crohn's disease [CD]: 163, age-at-diagnosis: 32.5 years; and indeterminate colitis [IC]: 10). Both hospital and outpatient records were collected and comprehensively reviewed. Adjusted mean incidence rates were 8.9/10(5) person-years for CD and 11.9/10(5) person-years in UC. Peak onset age in both CD and UC patients was 21-30 years old. Location at diagnosis in UC was proctitis in 26.8%, left-sided colitis in 50.9%, and pancolitis in 22.3%. The probability of proximal extension and colectomy after 5 years was 12.7% and 2.8%. The disease location in CD was ileal in 20.2%, colonic in 35.6%, ileocolonic in 44.2%, and upper gastrointestinal in four patients. Behavior at diagnosis was stenosing/penetrating in 35.6% and perianal in 11.1%. Patients with colonic disease were older at diagnosis compared to patients with ileal or ileocolonic disease. In a Kaplan-Meier analysis, probability of surgical resection was 9.8%, 18.5%, and 21.3% after 1, 3, and 5 years of disease duration, respectively. The incidence of IBD in Veszprem Province in the last decade was high, equal to that in high-incidence areas in Western European countries. Early disease course is milder compared to data reported in the literature. Copyright © 2011 Crohn's & Colitis Foundation of America, Inc.

Preimplantation Genetic Diagnosis for Stargardt Disease

Science.gov (United States)

Sohrab, Mahsa A.; Allikmets, Rando; Guarnaccia, Michael M.; Smith, R. Theodore

2010-01-01

Purpose To report the first use of in vitro fertilization (IVF) and preimplantation genetic diagnosis to achieve an unaffected pregnancy in an autosomal-recessive retinal dystrophy. Design Case report. Methods An affected male with Stargardt disease and his carrier wife underwent IVF. Embryos obtained by intracytoplasmic sperm injection underwent single-cell DNA testing via polymerase chain reaction and restriction enzyme analysis to detect the presence of ABCA4 mutant alleles. Embryos were diagnosed as being either affected by or carriers for Stargardt disease. A single carrier embryo was implanted. Results Chorionic villus sampling performed during the first trimester verified that the fetus possessed only one mutant paternal allele and one normal maternal allele, thus making her an unaffected carrier of the disease. A healthy, live-born female was delivered. Conclusion IVF and preimplantation genetic diagnosis can assist couples with an affected spouse and a carrier spouse with recessive retinal dystrophies to have an unaffected child. PMID:20149343

Ophthalmic examination in early diagnosis of Alzheimer's disease

Directory of Open Access Journals (Sweden)

Xin Li

2018-02-01

Full Text Available Alzheimer's disease is a progressive neurodegenerative disorder causing irreversible deterioration in memory and loss of self-care ability, which is seriously affecting the quality of life. There is no cure for Alzheimer's disease. Medication only can control the progression of the disease. Early diagnosis and control of disease progress is of great significance in improving the quality of life of the patients and reducing the burden of family and society. Ophthalmic examination is seen as a window which can “see” brain directly, and some changes in the eye can reflect the changes of the brain most directly. This paper reviews the ophthalmic examination of Alzheimer's disease, including optical coherence tomography(OCT, visual field, contrast sensitivity and eye movements, et al. We hope to provide a new idea for the early diagnosis of Alzheimer's disease.

Diagnosis of Fanconi Anemia: Mutation Analysis by Next-Generation Sequencing

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Najim Ameziane

2012-01-01

Full Text Available Fanconi anemia (FA is a rare genetic instability syndrome characterized by developmental defects, bone marrow failure, and a high cancer risk. Fifteen genetic subtypes have been distinguished. The majority of patients (≈85% belong to the subtypes A (≈60%, C (≈15% or G (≈10%, while a minority (≈15% is distributed over the remaining 12 subtypes. All subtypes seem to fit within the “classical” FA phenotype, except for D1 and N patients, who have more severe clinical symptoms. Since FA patients need special clinical management, the diagnosis should be firmly established, to exclude conditions with overlapping phenotypes. A valid FA diagnosis requires the detection of pathogenic mutations in a FA gene and/or a positive result from a chromosomal breakage test. Identification of the pathogenic mutations is also important for adequate genetic counselling and to facilitate prenatal or preimplantation genetic diagnosis. Here we describe and validate a comprehensive protocol for the molecular diagnosis of FA, based on massively parallel sequencing. We used this approach to identify BRCA2, FANCD2, FANCI and FANCL mutations in novel unclassified FA patients.

Successful preimplantation genetic diagnosis by targeted next-generation sequencing on an ion torrent personal genome machine platform.

Science.gov (United States)

Hao, Yan; Chen, Dawei; Zhang, Zhiguo; Zhou, Ping; Cao, Yunxia; Wei, Zhaolian; Xu, Xiaofeng; Chen, Beili; Zou, Weiwei; Lv, Mingrong; Ji, Dongmei; He, Xiaojin

2018-04-01

Hearing loss may place a heavy burden on the patient and patient's family. Given the high incidence of hearing loss among newborns and the huge cost of treatment and care (including cochlear implantation), prenatal diagnosis is strongly recommended. Termination of the fetus may be considered as an extreme outcome to the discovery of a potential deaf fetus, and therefore preimplantation genetic diagnosis has become an important option for avoiding the birth of affected children without facing the risk of abortion following prenatal diagnosis. In one case, a couple had a 7-year-old daughter affected by non-syndromic sensorineural hearing loss. The affected fetus carried a causative compound heterozygous mutation c.919-2 A>G (IVS7-2 A>G) and c.1707+5 G>A (IVS15+5 G>A) of the solute carrier family 26 member 4 gene inherited from maternal and paternal sides, respectively. The present study applied multiple displacement amplification for whole genome amplification of biopsied trophectoderm cells and next-generation sequencing (NGS)-based single nucleotide polymorphism haplotyping on an Ion Torrent Personal Genome Machine. One unaffected embryo was transferred in a frozen-thawed embryo transfer cycle and the patient was impregnated. To conclude, to the best of our knowledge, this may be the first report of NGS-based preimplantation genetic diagnosis (PGD) for non-syndromic hearing loss caused by a compound heterozygous mutation using an Ion Torrent Personal Genome Machine. NGS provides unprecedented high-throughput, highly parallel and base-pair resolution data for genetic analysis. The method meets the requirements of medium-sized diagnostics laboratories. With decreased costs compared with previous techniques (such as Sanger sequencing), this technique may have potential widespread clinical application in PGD of other types of monogenic disease.

Pneumococcal Disease: Diagnosis and Treatment

Science.gov (United States)

... the cause. In the case of pneumococcal disease, antibiotics can help prevent severe illness. Diagnosis If doctors suspect invasive ... In addition to the vaccine, appropriate use of antibiotics may also slow or reverse drug-resistant pneumococcal infections. Related Links ... Formats Help: How do I view different file formats (PDF, ...

Potts disease: Diagnosis with magnetic resonance imaging

Energy Technology Data Exchange (ETDEWEB)

Pursey, Jacqueline [MRI Department, Gartnavel General Hospitial, 1053 Great Western road, Glasgow G12 0YN (United Kingdom)], E-mail: Jacqueline.pursey@ggc.scot.nhs.uk; Stewart, Sharon [School of Health and Social Care, Caledonian University, Glasgow (United Kingdom)

2010-02-15

The eponymously named Potts disease is a relatively rare form of Tuberculosis (TB) which affects the spine. TB of the spine is one of the earliest diseases known to man and in the 20th century was thought to be a disease which had been defeated by the advent of antitubercular drugs. Over the last two decades there have been several reports which indicate a revival of TB in both the developing and developed world. Factors which may be contributing to this are the spread of the HIV virus, increased immigration and the emergence of drug resistant strains of the TB bacteria. Potts disease has an insidious onset and often the radiographic findings are far advanced when a diagnosis is finally reached. MRI is able to detect changes to the vertebrae in Potts disease earlier than radiographs. This case report outlines the clinical presentation of a young male with Potts disease who was HIV negative, and the important role that MRI plays in diagnosis and therefore in appropriate and timely intervention. The typical magnetic resonance (MR) imaging features and the radiographic hallmarks of the disease will also be discussed.

Potts disease: Diagnosis with magnetic resonance imaging

International Nuclear Information System (INIS)

Pursey, Jacqueline; Stewart, Sharon

2010-01-01

The eponymously named Potts disease is a relatively rare form of Tuberculosis (TB) which affects the spine. TB of the spine is one of the earliest diseases known to man and in the 20th century was thought to be a disease which had been defeated by the advent of antitubercular drugs. Over the last two decades there have been several reports which indicate a revival of TB in both the developing and developed world. Factors which may be contributing to this are the spread of the HIV virus, increased immigration and the emergence of drug resistant strains of the TB bacteria. Potts disease has an insidious onset and often the radiographic findings are far advanced when a diagnosis is finally reached. MRI is able to detect changes to the vertebrae in Potts disease earlier than radiographs. This case report outlines the clinical presentation of a young male with Potts disease who was HIV negative, and the important role that MRI plays in diagnosis and therefore in appropriate and timely intervention. The typical magnetic resonance (MR) imaging features and the radiographic hallmarks of the disease will also be discussed.

Noninvasive prenatal diagnosis of fetal trisomy 18 and trisomy 13 by maternal plasma DNA sequencing.

NARCIS (Netherlands)

Chen, E.Z.; Chiu, R.W.; Sun, H; Akolekar, R.; Chan, K.C.; Leung, T.Y.; Jiang, P.; Zheng, Y.W.; Lun, F.M.; Chan, L.Y.; Jin, Y.; Go, A.T.; Lau, E.T; To, W.W.; Leung, W.C.; Tang, R.Y.; Au-Yeung, S.K.; Lam, H.; Kung, Y.Y.; Zhang, X.; Vugt, J.M.G. van; Minekawa, R.; Tang, M.H.; Wang, J.; Oudejans, C.B.; Lau, T.K.; Nicolaides, K.H.; Lo, Y.M.

2011-01-01

Massively parallel sequencing of DNA molecules in the plasma of pregnant women has been shown to allow accurate and noninvasive prenatal detection of fetal trisomy 21. However, whether the sequencing approach is as accurate for the noninvasive prenatal diagnosis of trisomy 13 and 18 is unclear due

Disease Diagnosis in Smart Healthcare: Innovation, Technologies and Applications

Directory of Open Access Journals (Sweden)

Kwok Tai Chui

2017-12-01

Full Text Available To promote sustainable development, the smart city implies a global vision that merges artificial intelligence, big data, decision making, information and communication technology (ICT, and the internet-of-things (IoT. The ageing issue is an aspect that researchers, companies and government should devote efforts in developing smart healthcare innovative technology and applications. In this paper, the topic of disease diagnosis in smart healthcare is reviewed. Typical emerging optimization algorithms and machine learning algorithms are summarized. Evolutionary optimization, stochastic optimization and combinatorial optimization are covered. Owning to the fact that there are plenty of applications in healthcare, four applications in the field of diseases diagnosis (which also list in the top 10 causes of global death in 2015, namely cardiovascular diseases, diabetes mellitus, Alzheimer’s disease and other forms of dementia, and tuberculosis, are considered. In addition, challenges in the deployment of disease diagnosis in healthcare have been discussed.

Diagnosis of Alzheimer's disease in Brazil: Supplementary exams

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Paulo Caramelli

Full Text Available Abstract This article presents a review of the recommendations on supplementary exams employed for the clinical diagnosis of Alzheimer's disease (AD in Brazil published in 2005. A systematic assessment of the consensus reached in other countries, and of articles on AD diagnosis in Brazil available on the PUBMED and LILACS medical databases, was carried out. Recommended laboratory exams included complete blood count, serum creatinine, thyroid stimulating hormone (TSH, albumin, hepatic enzymes, Vitamin B12, folic acid, calcium, serological reactions for syphilis and serology for HIV in patients aged younger than 60 years with atypical clinical signs or suggestive symptoms. Structural neuroimaging, computed tomography or - preferably - magnetic resonance exams, are indicated for diagnostic investigation of dementia syndrome to rule out secondary etiologies. Functional neuroimaging exams (SPECT and PET, when available, increase diagnostic reliability and assist in the differential diagnosis of other types of dementia. The cerebrospinal fluid exam is indicated in cases of pre-senile onset dementia with atypical clinical presentation or course, for communicant hydrocephaly, and suspected inflammatory, infectious or prion disease of the central nervous system. Routine electroencephalograms aid the differential diagnosis of dementia syndrome with other conditions which impair cognitive functioning. Genotyping of apolipoprotein E or other susceptibility polymorphisms is not recommended for diagnostic purposes or for assessing the risk of developing the disease. Biomarkers related to the molecular alterations in AD are largely limited to use exclusively in research protocols, but when available can contribute to improving the accuracy of diagnosis of the disease.

Differential diagnosis of granulomatous lung disease: clues and pitfalls

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Shinichiro Ohshimo

2017-09-01

Full Text Available Granulomatous lung diseases are a heterogeneous group of disorders that have a wide spectrum of pathologies with variable clinical manifestations and outcomes. Precise clinical evaluation, laboratory testing, pulmonary function testing, radiological imaging including high-resolution computed tomography and often histopathological assessment contribute to make a confident diagnosis of granulomatous lung diseases. Differential diagnosis is challenging, and includes both infectious (mycobacteria and fungi and noninfectious lung diseases (sarcoidosis, necrotising sarcoid granulomatosis, hypersensitivity pneumonitis, hot tub lung, berylliosis, granulomatosis with polyangiitis, eosinophilic granulomatosis with polyangiitis, rheumatoid nodules, talc granulomatosis, Langerhans cell histiocytosis and bronchocentric granulomatosis. Bronchoalveolar lavage, endobronchial ultrasound-guided transbronchial needle aspiration, transbronchial cryobiopsy, positron emission tomography and genetic evaluation are potential candidates to improve the diagnostic accuracy for granulomatous lung diseases. As granuloma alone is a nonspecific histopathological finding, the multidisciplinary approach is important for a confident diagnosis.

The value of MR enteroclysis with air infusion in the diagnosis of small bowel disease

International Nuclear Information System (INIS)

Zhang Shizheng; Ren Xiaojun; Zhang Qiaowei

2004-01-01

Objective: To investigate the value of MR enteroclysis with air infusion in the diagnosis of small bowel disease. Methods: Sixteen patients with suspected small bowel disease, but without acute inflammatory disease or bowel obstruction, received MR enteroclysis with air infusion. There were 12 males and 4 females, and their age ranged from 17 to 75 years. 10 patients had abdominal pain, 4 with melena or blood stool, and 2 with diarrhea. The longest course was 7 years, and the shortest 1 week. Before MR imaging, a nasoenteric catheter was inserted into the distal part of duodenum, and about 1000 ml of air was infused through the tube to distend the small bowel. 20 mg of IV anisodamine was given to reduce small-bowel peristalsis. All patients were imaged with fat-saturated Gd-DTPA enhanced coronal and axial T 1 -weighted spin-echo (SE) sequence and fast spoiled gradient echo (FSPGR) sequence. Comparison between the diagnosis of MRI and the results of surgery, pathology or clinic was performed to assess the sensitivity and specificity of MRI. Results: 5 cases were normal, 6 with Crohn disease, 2 with gastric intestinal stromal tumor (GIST), and 1 each of lymphoma, tuberculosis and irritable bowel syndrome. The lumen of normal small bowel in MR enteroclysis was no signal, the wall was outlined as middle signal by intraluminal air and surrounding air-distended bowel and was between 1-3 mm thick, and the diameter of the lumen was between 17-28 mm. Crohn disease showed segmental mural thickening, increased enhancement, luminal stricture, and even extraluminal inflammatory mass or fistula. Intestinal tuberculosis invaded the distal section of ileum, cecum, and the proximal ascending colon, the wall thickened and enhanced apparently, and cecum and proximal ascending colon shortened. GIST showed a mass that was iso-signal on T 1 WI, high signal on T 2 WI, and enhanced significantly after IV Gd-DTPA. 1 recurrent lymphoma of ileum showed mural thickening and increased

Atypical case of Wolfram syndrome revealed through targeted exome sequencing in a patient with suspected mitochondrial disease.

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Lieber, Daniel S; Vafai, Scott B; Horton, Laura C; Slate, Nancy G; Liu, Shangtao; Borowsky, Mark L; Calvo, Sarah E; Schmahmann, Jeremy D; Mootha, Vamsi K

2012-01-06

Mitochondrial diseases comprise a diverse set of clinical disorders that affect multiple organ systems with varying severity and age of onset. Due to their clinical and genetic heterogeneity, these diseases are difficult to diagnose. We have developed a targeted exome sequencing approach to improve our ability to properly diagnose mitochondrial diseases and apply it here to an individual patient. Our method targets mitochondrial DNA (mtDNA) and the exons of 1,600 nuclear genes involved in mitochondrial biology or Mendelian disorders with multi-system phenotypes, thereby allowing for simultaneous evaluation of multiple disease loci. Targeted exome sequencing was performed on a patient initially suspected to have a mitochondrial disorder. The patient presented with diabetes mellitus, diffuse brain atrophy, autonomic neuropathy, optic nerve atrophy, and a severe amnestic syndrome. Further work-up revealed multiple heteroplasmic mtDNA deletions as well as profound thiamine deficiency without a clear nutritional cause. Targeted exome sequencing revealed a homozygous c.1672C > T (p.R558C) missense mutation in exon 8 of WFS1 that has previously been reported in a patient with Wolfram syndrome. This case demonstrates how clinical application of next-generation sequencing technology can enhance the diagnosis of patients suspected to have rare genetic disorders. Furthermore, the finding of unexplained thiamine deficiency in a patient with Wolfram syndrome suggests a potential link between WFS1 biology and thiamine metabolism that has implications for the clinical management of Wolfram syndrome patients.

Atypical case of Wolfram syndrome revealed through targeted exome sequencing in a patient with suspected mitochondrial disease

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Lieber Daniel S

2012-01-01

Full Text Available Abstract Background Mitochondrial diseases comprise a diverse set of clinical disorders that affect multiple organ systems with varying severity and age of onset. Due to their clinical and genetic heterogeneity, these diseases are difficult to diagnose. We have developed a targeted exome sequencing approach to improve our ability to properly diagnose mitochondrial diseases and apply it here to an individual patient. Our method targets mitochondrial DNA (mtDNA and the exons of 1,600 nuclear genes involved in mitochondrial biology or Mendelian disorders with multi-system phenotypes, thereby allowing for simultaneous evaluation of multiple disease loci. Case Presentation Targeted exome sequencing was performed on a patient initially suspected to have a mitochondrial disorder. The patient presented with diabetes mellitus, diffuse brain atrophy, autonomic neuropathy, optic nerve atrophy, and a severe amnestic syndrome. Further work-up revealed multiple heteroplasmic mtDNA deletions as well as profound thiamine deficiency without a clear nutritional cause. Targeted exome sequencing revealed a homozygous c.1672C > T (p.R558C missense mutation in exon 8 of WFS1 that has previously been reported in a patient with Wolfram syndrome. Conclusion This case demonstrates how clinical application of next-generation sequencing technology can enhance the diagnosis of patients suspected to have rare genetic disorders. Furthermore, the finding of unexplained thiamine deficiency in a patient with Wolfram syndrome suggests a potential link between WFS1 biology and thiamine metabolism that has implications for the clinical management of Wolfram syndrome patients.

Whole-Genome Sequences of Thirteen Isolates of Borrelia burgdorferi

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Schutzer S. E.; Dunn J.; Fraser-Liggett, C. M.; Casjens, S. R.; Qiu, W.-G.; Mongodin, E. F.; Luft, B. J.

2011-02-01

Borrelia burgdorferi is a causative agent of Lyme disease in North America and Eurasia. The first complete genome sequence of B. burgdorferi strain 31, available for more than a decade, has assisted research on the pathogenesis of Lyme disease. Because a single genome sequence is not sufficient to understand the relationship between genotypic and geographic variation and disease phenotype, we determined the whole-genome sequences of 13 additional B. burgdorferi isolates that span the range of natural variation. These sequences should allow improved understanding of pathogenesis and provide a foundation for novel detection, diagnosis, and prevention strategies.

SIGNIFICANCE OF TARGETED EXOME SEQUENCING AND METHODS OF DATA ANALYSIS IN THE DIAGNOSIS OF GENETIC DISORDERS LEADING TO THE DEVELOPMENT OF EPILEPTIC ENCEPHALOPATHY

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Tatyana Victorovna Kozhanova

2017-08-01

Full Text Available Epilepsy is the most common serious neurological disorder, and there is a genetic basis in almost 50% of people with epilepsy. The diagnosis of genetic epilepsies makes to estimate reasons of seizures in the patient. Last decade has shown tremendous growth in gene sequencing technologies, which have made genetic tests available. The aim is to show significance of targeted exome sequencing and methods of data analysis in the diagnosis of hereditary syndromes leading to the development of epileptic encephalopathy. We examined 27 patients with с early EE (resistant to antiepileptic drugs, psychomotor and speech development delay in the psycho-neurological department. Targeted exome sequencing was performed for patients without a previously identified molecular diagnosis using 454 Sequencing GS Junior sequencer (Roche and IlluminaNextSeq 500 platform. As a result of the analysis, specific epilepsy genetic variants were diagnosed in 27 patients. The greatest number of cases was due to mutations in the SCN1A gene (7/27. The structure of mutations for other genes (mutations with a minor allele frequency of less than 0,5% are presented: ALDH7A1 (n=1, CACNA1C (n=1, CDKL5 (n=1, CNTNAP2 (n=2, DLGAP2 (n=2, DOCK7 (n=2, GRIN2B (n=2, HCN1 (n=1, NRXN1 (n=3, PCDH19 (n=1, RNASEH2B (n=2, SLC2A1 (n=1, UBE3A (n=1. The use of the exome sequencing in the genetic practice allows to significantly improve the effectiveness of medical genetic counseling, as it made possible to diagnose certain variants of genetically heterogeneous groups of diseases with similar of clinical manifestations.

Genomics and epigenomics in rheumatic diseases: what do they provide in terms of diagnosis and disease management?

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Castro-Santos, Patricia; Díaz-Peña, Roberto

2017-09-01

Most rheumatic diseases are complex or multifactorial entities with pathogeneses that interact with both multiple genetic factors and a high number of diverse environmental factors. Knowledge of the human genome sequence and its diversity among populations has provided a crucial step forward in our understanding of genetic diseases, identifying many genetic loci or genes associated with diverse phenotypes. In general, susceptibility to autoimmunity is associated with multiple risk factors, but the mechanism of the environmental component influence is poorly understood. Studies in twins have demonstrated that genetics do not explain the totality of the pathogenesis of rheumatic diseases. One method of modulating gene expression through environmental effects is via epigenetic modifications. These techniques open a new field for identifying useful new biomarkers and therapeutic targets. In this context, the development of "-omics" techniques is an opportunity to progress in our knowledge of complex diseases, impacting the discovery of new potential biomarkers suitable for their introduction into clinical practice. In this review, we focus on the recent advances in the fields of genomics and epigenomics in rheumatic diseases and their potential to be useful for the diagnosis, follow-up, and treatment of these diseases. The ultimate aim of genomic studies in any human disease is to understand its pathogenesis, thereby enabling the prediction of the evolution of the disease to establish new treatments and address the development of personalized therapies.

Diagnosis and Updates in Celiac Disease.

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Shannahan, Sarah; Leffler, Daniel A

2017-01-01

Celiac disease is an autoimmune disorder induced by gluten in genetically susceptible individuals. It can result in intraintestinal and extraintestinal manifestations of disease including diarrhea, weight loss, anemia, osteoporosis, or lymphoma. Diagnosis of celiac disease is made through initial serologic testing and then confirmed by histopathologic examination of duodenal biopsies. Generally celiac disease is a benign disorder with a good prognosis in those who adhere to a gluten-free diet. However, in refractory disease, complications may develop that warrant additional testing with more advanced radiologic and endoscopic methods. This article reviews the current strategy to diagnose celiac disease and the newer modalities to assess for associated complications. Copyright © 2016 Elsevier Inc. All rights reserved.

Diagnosis of thyroid diseases. The diagnosis value of the various methods of examination

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Pfannenstiel, P [Stiftung Deutsche Klinik fuer Diagnostik, Wiesbaden (Germany, F.R.). Fachbereich Nuklearmedizin

1980-03-01

The recommendations of the thyroid section of the Deutsche Gesellschaft fuer Endokrinologie take account of practical requirements and serve as a basis for assessing the indications of the various diagnostic methods in view of their value, expenditure, and hazards. Progress in methodology and recent scientific findings have been taken into account as well as economic aspects and the available equipment. In spite of all the possibilities offered by modern laboratory diagnosis, the diagnosis and theory of thyroid diseases should always depend on a special anamnesis and a physical examination of the patient. The measured values must agree with the patient's complaints and with clinical findings. In diagnoses involving several steps, one should always start with simple in-vitro techniques in order to spare the patient stress. Functional diagnosis of thyroid diseases are supplemented by thyroid scintiscanning with short-lived radionuclides and by thyroid cytology. Experience and precise knowledge help to 'save expense and radiation'. Of course, uncertain diagnoses and untypical findings require a more extensive use of diagnostic means than diagnosis that are more or less clinically proved.

Granulomas at initial diagnosis of Crohn's disease signal a poor ...

African Journals Online (AJOL)

CD patients (n=101) with uncomplicated non-stricturing, non-penetrating disease at diagnosis, and with follow-up >5 years, were retrospectively analysed using a predefined definition of severe CD (SCD) over the disease course. Clinical, demographic, laboratory and histological factors at diagnosis associated with SCD ...

Simplifying Skin Disease Diagnosis with Topical Nanotechnology.

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Yeo, David C; Xu, Chenjie

2018-05-01

A new study published in the journal Nature Biomedical Engineering 1 documents a novel diagnostic technology that exploits topically applied nanotechnology to detect skin tissue biomarkers for diagnosis. This concept is demonstrated by noninvasively imaging connective tissue growth factor (CTGF) mRNA in abnormal scar cells, whole tissue, and animal models. In this commentary, we highlight the main findings and discuss their implications. Successful implementation in the clinic could give rise to self-applied, biopsy-free diagnostic technology and significantly reduce healthcare burden. Crucially, noninvasive visualization of disease biomarkers, mobile device signal acquisition, and Internet-enabled transmission could significantly transform the diagnosis of skin disease and other superficial tissues.

Molecular diagnosis of lyssaviruses and sequence comparison of Australian bat lyssavirus samples.

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Foord, A J; Heine, H G; Pritchard, L I; Lunt, R A; Newberry, K M; Rootes, C L; Boyle, D B

2006-07-01

To evaluate and implement molecular diagnostic tests for the detection of lyssaviruses in Australia. A published hemi-nested reverse transcriptase polymerase chain reaction (RT-PCR) for the detection of all lyssavirus genotypes was modified to a fully nested RT-PCR format and compared with the original assay. TaqMan assays for the detection of Australian bat lyssavirus (ABLV) were compared with both the nested and hemi-nested RT-PCR assays. The sequences of RT-PCR products were determined to assess sequence variations of the target region (nucleocapsid gene) in samples of ABLV originating from different regions. The nested RT-PCR assay was highly analytically specific, and at least as analytically sensitive as the hemi-nested assay. The TaqMan assays were highly analytically specific and more analytically sensitive than either RT-PCR assay, with a detection level of approximately 10 genome equivalents per microl. Sequence of the first 544 nucleotides of the nucleocapsid protein coding sequence was obtained from all samples of ABLV received at Australian Animal Health Laboratory during the study period. The nested RT-PCR provided a means for molecular diagnosis of all tested genotypes of lyssavirus including classical rabies virus and Australian bat lyssavirus. The published TaqMan assay proved to be superior to the RT-PCR assays for the detection of ABLV in terms of analytical sensitivity. The TaqMan assay would also be faster and cross contamination is less likely. Nucleotide sequence analyses of samples of ABLV from a wide geographical range in Australia demonstrated the conserved nature of this region of the genome and therefore the suitability of this region for molecular diagnosis.

Next-generation sequencing-based molecular diagnosis of chronic non-spherocytic hemolysis in erythrocytic enzymopathies

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Manu Jamwal

2017-10-01

Full Text Available Mutations in genes encoding red blood cell enzymes are often inherited in an autosomal recessive manner and can lead to chronic nonspherocytic hemolytic anemia (CNSHA in homozygotes and compound heterozygotes. Usual clinical manifestations include jaundice, cholelithiasis and splenomegaly with normocytic normochromic hemolysis. Phenotypes range from fully-compensated hemolysis (without anemia to transfusion-dependent states. Definitive diagnosis requires biochemical testing of enzyme levels, which for rarer enzymes are often difficult and not easily available. Molecular diagnosis using a gene-by-gene approach is expensive, time-consuming and cumbersome. Targeted resequencing can expedite the molecular diagnosis in cases where the hemolysis remains unexplained after routine laboratory tests. Ten patients with clinical and laboratory evidence suggestive of hemolytic anemia, but negative family history, were enrolled. Various biochemical and molecular tests were used to exclude glucose-6-phosphate dehydrogenase (G6PD deficiency, thalassemias, hemoglobinopathies, autoimmune hemolysis, hereditary spherocytosis and pyruvate kinase (PKLR deficiency. Common G6PD and PKLR variants were excluded by molecular tests. DNA Libraries were prepared using TruSight One™ panel and sequenced on MiSeq™ Sequencing System. MiSeq Reporter™ and VariantStudio™ v2.1 were used for analysis, classification, and reporting of genomic variants reporting genomic variants. All 10 patients’ diagnoses were resolved by targeted resequencing: two had G6PD deficiency, two had glucose-6-phosphate isomerase (GPI deficiency and six unexpectedly had pyruvate kinase deficiency despite pyruvate kinase enzyme activity assays previously being normal in all. All the mutations were predicted deleterious by PolyPhen, SIFT, Provean, mutpred and Mutationtaster software. The mutations were validated in parents and/or siblings (where available to establish the mode of inheritance. Our

Diagnosis of ischaemic heart disease with thallium-201

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Human, G P [Pretoria Univ. (South Africa). Dept. of Internal Medicine; Dormehl, I [Atomic Energy Board, Pelindaba, Pretoria (South Africa). Life Sciences Div.

1981-04-04

Thallium-201 is very suitable for cardiac imaging because of its physical characteristics and biological behaviour. Perfusion defects caused by ischaemia, necrosis or fibrosis are represented by 'cold spots' on the myocardial scan. In this article we report our experience with this method in the diagnosis of ischaemic heart disease in 117 patients. Excellent correlation was found with clinical, electrocardiographic and angiographic parameters. Both sensitivity and specificity for the diagnosis of ischaemic heart disease were higher with /sup 201/Tl scintigraphy than with existing diagnostic methods.

Fox Den Disease: An Interesting Case Following Delayed Diagnosis.

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Stehr, Ryan C; Kim, Nicholas; LoGiudice, John A; Ludwig, Kirk

2015-06-01

Pyoderma fistulans sinifica, also known as fox den disease, is a rare and poorly understood inflammatory disorder of the skin and subcutaneous tissues. This disorder is often mistaken for other inflammatory skin disorders and treated inappropriately. The authors describe the case of a 53-year-old male who presented to the colorectal surgery service with a longstanding diagnosis of perirectal Crohn's disease. Despite aggressive immunosuppression and numerous surgical procedures, the patient continued to have unrelenting purulent drainage from the skin of his buttocks. Following wide excision of the affected skin and subcutaneous tissues by the colorectal surgeon, the plastic surgery team reconstructed the 30 cm x 55 cm wound using a combination of local flaps and skin grafts. The initial pathology report of the excised specimen confirmed the presence of nonspecific abscesses and inflammation. Upon special request by the plastic surgery team, the sample was resectioned with the specific intent of establishing a diagnosis of fox den disease. The additional slides met the criteria for an unequivocal diagnosis of fox den disease. Immunosuppression was discontinued and the patient healed his wounds without complication. Fox den disease is often overlooked because of the obscurity of the disease and the special histological sectioning needed to establish a diagnosis. In this case, the patient was unnecessarily treated with immunosuppressive drugs for more than 3 decades because of a misdiagnosis. With increased awareness of fox den disease, perhaps its pathophysiology can be better elucidated as more patients are appropriately diagnosed and treated.

Diagnosis and treatment of Alzheimer's disease

International Nuclear Information System (INIS)

Hampel, H.; Padberg, F.; Koetter, H.U.; Teipel, S.J.; Ehrhardt, T.; Hegerl, U.; Stuebner, S.; Moeller, H.J.

1997-01-01

Alzheimer's disease is often diagnosed too late. Its etiology is still largely unknown and remains one of the big challenges in neurobiological fundamental research. Optimized early and differential diagnosis can be ensured by a dynamic concept of multidisciplinary diagnosis in cooperation between practitioners specializing in brain disorders, clinical psychogeriatric deprtments, and general practitioners. This, in turn, will enable individualized planning of further living conditions and care of Alzheimer patients and their relations as well as efficient and early pharmacotherapy and psychological intervention. (orig) [de

Parkinsonian syndroms: Clinical phenotype, differential diagnosis and disease progression

International Nuclear Information System (INIS)

Storch, A.

2002-01-01

Parkinsonian syndromes include idiopathic Parkinson's disease (IPD), other neurodegenerative diseases with parkinsonism, the so-called atypical parkinsonian syndromes, and symptomatic parkinsonian syndromes, such as Wilson's disease. IPD is the most frequent disease with parkinsonism as the main clinical feature and is responsible for approx. 80% of all parkinsonian syndromes. Atypical parkinsonian syndromes are the most important differential diagnoses of IPD. The two most frequent types are multiple system atrophy (MSA) and progressive supranuclear palsy (PSP). For clinical diagnosis it is essential to take a careful medical history and to examine the patients physically in regular intervals. However, various clinico-pathological studies have shown that approx. 25% of patients with clinical diagnosis of IPD may have other causes of parkinsonism. Selected technical investigations, in particular functional imaging of the central dopaminergic system using PET or SPECT, may help to make clinical diagnosis more secure. This paper reviews the clinical features and diagnostic findings in diseases with parkinsonism and summarises the difficulties in establishing early and differential diagnoses. (orig.) [de

[Preimplantation genetic diagnosis and monogenic inherited eye diseases].

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Hlavatá, L; Ďuďáková, Ľ; Trková, M; Soldátová, I; Skalická, P; Kousal, B; Lišková, P

Preimplantation genetic diagnosis (PGD) is an established application of genetic testing in the context of in vitro fertilization. PGD is an alternative method to prenatal diagnosis which aims to prevent the transmission of an inherited disorder to the progeny by implanting only embryos that do not carry genetic predisposition for a particular disease. The aim of this study is to provide an overview of eye disorders for which PGD has been carried out. The European literature search focused on best practices, ethical issues, risks and results of PGD for inherited eye disorders. PGD is performed for a number of ocular disorders; a prerequisite for its application is however, the knowledge of a disease-causing mutation(s). The main advantage of this method is that the couple is not exposed to a decision of whether or not to undergo an abortion. Qualified counselling must be provided prior to the PGD in order to completely understand the risk of disability in any child conceived, consequences of disease manifestation, and advantages as well as limitations of this method. In the group of non-syndromic eye diseases and diseases in which ocular findings dominate, PGD has been performed in European countries for aniridia, choroideremia, congenital fibrosis of extraocular muscles, Leber congenital amaurosis, ocular albinism, retinitis pigmentosa, X-linked retinoschisis, Stargardt disease, blepharophimosis-ptosis-inverse epicanthus syndrome and retinoblastoma. Sexing for X-linked or mitochondrial diseases has been carried out for blue cone monochromatism, choroideremia, familial exudative vitreoretinopathy, Leber hereditary optic neuropathy, macular dystrophy (not further specified), Norrie disease, X-linked congenital stationary night blindness, X-linked retinoschisis and nystagmus (not further specified). In recent years, there has been an increase in potential to use PGD. The spectrum of diseases for this method has widened to include severe inherited eye diseases

Challenges in the rabbit haemorrhagic disease 2 (RHDV2) molecular diagnosis of vaccinated rabbits.

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Carvalho, C L; Duarte, E L; Monteiro, M; Botelho, A; Albuquerque, T; Fevereiro, M; Henriques, A M; Barros, S S; Duarte, Margarida Dias

2017-01-01

Molecular methods are fundamental tools for the diagnosis of viral infections. While interpretation of results is straightforward for unvaccinated animals, where positivity represents ongoing or past infections, the presence of vaccine virus in the tissues of recently vaccinated animals may mislead diagnosis. In this study, we investigated the interference of RHDV2 vaccination in the results of a RT-qPCR for RHDV2 detection, and possible associations between mean Cq values of five animal groups differing in age, vaccination status and origin (domestic/wild). Viral sequences from vaccinated rabbits that died of RHDV2 infection (n=14) were compared with the sequences from the commercial vaccines used in those animals. Group Cq means were compared through Independent t-test and One-way ANOVA. We proved that RHDV2 vaccine-RNA is not detected by the RT-qPCR as early as 15days post-vaccination, an important fact in assisting results interpretation for diagnosis. Cq values of vaccinated and non-vaccinated infected domestic adults showed a statistically significant difference (pRHDV2-victimised rabbits. Although the reduced number of vaccinated young animals analysed hampered a robust statistical analysis, this occurrence suggests that passively acquired maternal antibodies may inhibit the active immune response to vaccination, delaying protection and favouring disease progression. Our finding emphasises the importance of adapting kitten RHDV2 vaccination schedules to circumvent this interference phenomenon. Copyright © 2016 Elsevier B.V. All rights reserved.

Roentgenosemiotics and diagnosis of human diseases

International Nuclear Information System (INIS)

Mikhajlov, A.N.

1989-01-01

Modern concepts concerning roentgenologic semiotics, diagnosis of almost all the human diseases as well as the features of roentgenologic examintion of organs and systems are described. Roentgenologic symptoms and syndroms are systematized and standardized by anatomy branches. 48 refs

FLAIR-HASTE sequence in differential diagnosis of focal hepatic lesions

International Nuclear Information System (INIS)

Kim, Yong Jae; Kim, Tae Kyoung; Bae, In Young; Kim, Pyo Nyun; Ha, Hyun Kwon; Kim, Ah Young; Lee, Moon Gyu

2001-01-01

To assess the feasibility of using the FLAIR (fluid-attenuated inversion recovery)-HASTE (half-fourier acquisition single-shot turbo spin-echo) sequence for the differential diagnosis of focal hepatic lesions. During a 12-month period, 80 patients with 127 focal hepatic lesions [hemangiomas (n=60), hepatocellular carcinomas (HCC) (n=27), cysts (n=25), and metastases (n=15) underwent MR imaging using a 1.5-T scanner. Verification of the diagnosis was based on the findings of pathology (n=11), of angiography and clinical investigation (n=17), or of dynamic contrast-enhanced MR imaging (n=99). MR sequences included T2-weighted HASTE (TE, 134 ms ; echo space, 4.4 ms), FLAIR-HASTE (TE, 64 ms ; echo space, 4.4 ms ; inversion time, 2000 ms ; number of slices, 5-9 ; acquisition time, 13-20 s), and dynamic gadolinium-enhanced T1-weighted FLASH (TR, 131 ms ; TE, 4 ms). FLAIR-HASTE imaging was of any focal lesions seen on T2-weighted HASTE images was performed in the liver area, and their signal intensity was classified in one of five ways : very high (higher than the spleen), moderately high (similar to the spleen), slightly high (higher than the liver and lower than the spleen), intermediate (similar to the liver), or low (lower than the liver). The signal intensity of the 25 cysts, as determined by FLAIR-HASTE, was low in 21 cases (84%), intermediate in three (12%), and very high in one (4%), which was diagnosed as a complicated cyst in which ultrasound revealed internal septa. At FLAIR-HASTE, all 60 hemangiomas showed either very high (n=50, 83%) or moderately high (n=10, 17%) signal intensity, while that of 42 hepatic malignant tumors was very high in 14 cases (33%), moderately high in 8 (19%), slightly high in 18 (43%), intermediate in one (2.5%), and low in one (2.5%). FLAIR-HASTE showed that the signal intensity of the majority of hepatic cysts was low, while that of most hemangiomas and solid liver tumors was high. For the differential diagnosis of cystic and

Advances in Diagnosis of Respiratory Diseases of Small Ruminants

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Sandip Chakraborty

2014-01-01

Full Text Available Irrespective of aetiology, infectious respiratory diseases of sheep and goats contribute to 5.6 percent of the total diseases of small ruminants. These infectious respiratory disorders are divided into two groups: the diseases of upper respiratory tract, namely, nasal myiasis and enzootic nasal tumors, and diseases of lower respiratory tract, namely, peste des petits ruminants (PPR, parainfluenza, Pasteurellosis, Ovine progressive pneumonia, mycoplasmosis, caprine arthritis encephalitis virus, caseous lymphadenitis, verminous pneumonia, and many others. Depending upon aetiology, many of them are acute and fatal in nature. Early, rapid, and specific diagnosis of such diseases holds great importance to reduce the losses. The advanced enzyme-linked immunosorbent assays (ELISAs for the detection of antigen as well as antibodies directly from the samples and molecular diagnostic assays along with microsatellites comprehensively assist in diagnosis as well as treatment and epidemiological studies. The present review discusses the advancements made in the diagnosis of common infectious respiratory diseases of sheep and goats. It would update the knowledge and help in adapting and implementing appropriate, timely, and confirmatory diagnostic procedures. Moreover, it would assist in designing appropriate prevention protocols and devising suitable control strategies to overcome respiratory diseases and alleviate the economic losses.

Clinical characterization and diagnosis of cystic fibrosis through exome sequencing in Chinese infants with Bartter-syndrome-like hypokalemia alkalosis.

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Qiu, Liru; Yang, Fengjie; He, Yonghua; Yuan, Huiqing; Zhou, Jianhua

2018-03-09

Cystic fibrosis (CF) is a fatal autosomal-recessive disease caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. CF is characterized by recurrent pulmonary infection with obstructive pulmonary disease. CF is common in the Caucasian population but is rare in the Chinese population. The symptoms of early-stage CF are often untypical and may sometimes manifest as Bartter syndrome (BS)-like hypokalemic alkalosis. Therefore, the ability of doctors to differentiate CF from BS-like hypokalemic alkalosis in Chinese infants is a great challenge in the timely and accurate diagnosis of CF. In China, sporadic CF has not been diagnosed in children younger than three years of age to date. Three infants, who were initially admitted to our hospital over the period of June 2013 to September 2014 with BS-like hypokalemic alkalosis, were diagnosed with CF through exome sequencing and sweat chloride measurement. The compound heterozygous mutations of the CFTR gene were detected in two infants, and a homozygous missense mutation was found in one infant. Among the six identified mutations, two are novel point mutations (c.1526G > C and c.3062C > T) that are possibly pathogenic. The three infants are the youngest Chinese patients to have been diagnosed with sporadic CF at a very early stage. Follow-up examination showed that all of the cases remained symptom-free after early intervention, indicating the potential benefit of very early diagnosis and timely intervention in children with CF. Our results demonstrate the necessity of distinguishing CF from BS in Chinese infants with hypokalemic alkalosis and the significant diagnostic value of powerful exome sequencing for rare genetic diseases. Furthermore, our findings expand the CFTR mutation spectrum associated with CF.

SYMPTOMS AND DIAGNOSIS OF HIRSCHSPRUNG’S DISEASE

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Putu Ayu Ines Lassiyani Surya

2014-02-01

Full Text Available Hirschsprung disease is a disease that attacks the human digestive system, mainly in the largeintestine (colon. In this disease, found enlargement of the colon (megacolon, due to the absenceof ganglion cells in the distal intestine. Hirschsprung disease often affects neonates and evenchildren, are often characterized by delays in spending the first meconium, bilious vomiting,abdominal distension. Methods diagnois do for Hirschsprung's disease was confirmed by biopsy,barium enema or contrast enema, and anorectal manometry. Early diagnosis is crucial to conductrapid and appropriate treatment and to prevent complications.

Coeliac disease: review of diagnosis and management.

Science.gov (United States)

Walker, Marjorie M; Ludvigsson, Jonas F; Sanders, David S

2017-08-21

Coeliac disease is an immune-mediated systemic disease triggered by exposure to gluten, and manifested by small intestinal enteropathy and gastrointestinal and extra-intestinal symptoms. Recent guidelines recommend a concerted use of clear definitions of the disease. In Australia, the most recent estimated prevalence is 1.2% in adult men (1:86) and 1.9% in adult women (1:52). Active case finding is appropriate to diagnose coeliac disease in high risk groups. Diagnosis of coeliac disease is important to prevent nutritional deficiency and long term risk of gastrointestinal malignancy. The diagnosis of coeliac disease depends on clinico-pathological correlation: history, presence of antitransglutaminase antibodies, and characteristic histological features on duodenal biopsy (when the patient is on a gluten-containing diet). Human leucocyte antigen class II haplotypes DQ2 or DQ8 are found in nearly all patients with coeliac disease, but are highly prevalent in the general population at large (56% in Australia) and testing can only exclude coeliac disease for individuals with non-permissive haplotypes. Adhering to a gluten free diet allows duodenal mucosal healing and alleviates symptoms. Patients should be followed up with a yearly review of dietary adherence and a health check. Non-coeliac gluten or wheat protein sensitivity is a syndrome characterised by both gastrointestinal and extra-intestinal symptoms related to the ingestion of gluten and possibly other wheat proteins in people who do not have coeliac disease or wheat allergy recognised by diagnostic tests.

Diagnosis of Celiac Disease: Taking a Bite Out of the Controversy.

Science.gov (United States)

Turner, Justine M

2018-06-01

Celiac disease is a common autoimmune disorder of the small intestine, triggered by an immunological response to the gluten present in wheat, barley, and rye in individuals who are genetically at risk. A key to reducing the complications of this disease is early diagnosis, preferably in childhood, and consuming a lifelong gluten-free diet once diagnosis is confirmed. Yet, the diagnosis of celiac disease is often considerably delayed, exposing patients to needless suffering and morbidity. It is also difficult to confirm histologically if dietary gluten has been restricted prior to obtaining a diagnostic biopsy, a significant problem given the current growing popularity of gluten-free diets. Furthermore, failure to understand or follow current guidelines means physicians may recommend patients commence the gluten-free diet before initiating referral to a gastroenterologist. Finally, adding further confusion, pediatric guidelines in Europe support a diagnosis based on serology rather than on histology, whereas those based in North America do not. The purpose of this review is to discuss these issues and other controversies in the diagnosis of celiac disease and to consider ways to optimize diagnosis across the lifespan.

Diagnosis, prognosis and disease management using in situ hybridization

International Nuclear Information System (INIS)

Kucheria, K.; Talwar, R.

2002-01-01

The year 2001 saw unveiling of anatomy of the human genome with sequencing of 90% of the euchromatic region. But the ultimate goal of the Human Genome Project to delineate the positions of all genes is yet to be achieved. In Situ Hybridization (ISH) is one of the methods that help in localizing genes on chromosomes. The present study aimed to use radioactive- and fluorescent-labeled probes for screening various congenital anomalies (sex chromosomal and autosomal), for prenatal diagnosis and cancer genetics. Standard techniques were used for hybridization with radioactively and fluorescent labeled probes. Sex chromosome aneuploidies (XXY, XO, XXX, XYY etc.) were analyzed using centromeric probes for chromosomes X and Y. The cases with ambiguous genitalia were further analyzed using probe specific for the sex-determining region (SRY) on the Y chromosome. Suspected cases of Down syndrome were analyzed using probe specific for centromeric region of chromosome 21 to confirm trisomy 21. Prenatal diagnosis included screening aneuploidies of chromosomes 13, 18, 21, X and Y on uncultured cells and metaphases obtained from amniotic fluid and chorionic villi samplings. Gene alterations were also studied in Retinoblastoma patients, Chronic Myeloid Leukemia (CML) and Acute Promyelocytic Leukemia (APML) using probes specific for Rb1, bcr/abl and PML/RARα genes respectively. Response to therapy was assessed by evaluating minimal residual disease (MRD) in leukemia patients. Attempts were also made to analyze cells obtained from buccal mucosa and bladder epithelium that could facilitate rapid screening of sex chromosome anomalies and bladder cancer without painful invasive techniques. Prenatal diagnosis using ISH on uncultured cells could provide an accurate and rapid result. These results of prenatal diagnosis were in conformation with results of conventional cytogenetics obtained after long-term cultures. Molecular rearrangements that could not be detected with conventional

ACG clinical guidelines: diagnosis and management of celiac disease.

Science.gov (United States)

Rubio-Tapia, Alberto; Hill, Ivor D; Kelly, Ciarán P; Calderwood, Audrey H; Murray, Joseph A

2013-05-01

This guideline presents recommendations for the diagnosis and management of patients with celiac disease. Celiac disease is an immune-based reaction to dietary gluten (storage protein for wheat, barley, and rye) that primarily affects the small intestine in those with a genetic predisposition and resolves with exclusion of gluten from the diet. There has been a substantial increase in the prevalence of celiac disease over the last 50 years and an increase in the rate of diagnosis in the last 10 years. Celiac disease can present with many symptoms, including typical gastrointestinal symptoms (e.g., diarrhea, steatorrhea, weight loss, bloating, flatulence, abdominal pain) and also non-gastrointestinal abnormalities (e.g., abnormal liver function tests, iron deficiency anemia, bone disease, skin disorders, and many other protean manifestations). Indeed, many individuals with celiac disease may have no symptoms at all. Celiac disease is usually detected by serologic testing of celiac-specific antibodies. The diagnosis is confirmed by duodenal mucosal biopsies. Both serology and biopsy should be performed on a gluten-containing diet. The treatment for celiac disease is primarily a gluten-free diet (GFD), which requires significant patient education, motivation, and follow-up. Non-responsive celiac disease occurs frequently, particularly in those diagnosed in adulthood. Persistent or recurring symptoms should lead to a review of the patient's original diagnosis to exclude alternative diagnoses, a review of the GFD to ensure there is no obvious gluten contamination, and serologic testing to confirm adherence with the GFD. In addition, evaluation for disorders associated with celiac disease that could cause persistent symptoms, such as microscopic colitis, pancreatic exocrine dysfunction, and complications of celiac disease, such as enteropathy-associated lymphoma or refractory celiac disease, should be entertained. Newer therapeutic modalities are being studied in

Research progress in early diagnosis of Alzheimer's disease

Directory of Open Access Journals (Sweden)

Meng-sha SUN

2018-04-01

Full Text Available Alzheimer's disease (AD is a kind of central nervous system degenerative disease with higher incidence, which has been paid increasing attention. The pathogenesis is not yet clear though it has been studied a lot. The existing theories focused on amyloid β-protein (Aβ deposit, hyperphosphorylation of tau and cholinergic neuronal loss. There is mainly symptomatic treatment which cannot reverse disease course. So early diagnosis is particularly important for prevention and treatment of AD. The article will review recent advances in the studies of early diagnosis of AD. It may help accurately diagnose the process from mild cognitive impairment (MCI to early AD and give advice on prevention and treatment. DOI: 10.3969/j.issn.1672-6731.2018.03.011

Diagnosis and therapy of coronary artery disease: Second edition

International Nuclear Information System (INIS)

Cohn, P.F.

1985-01-01

This book contains 18 selections. Some of the titles are: Nuclear cardiology; Diagnosis of acute myocardial infarction; Therapy of angina pectoris; Psychosocial aspects of coronary artery disease; Nonatherosclerotic coronary artery disease; and The epidemiology of coronary artery disease

Application of massively parallel sequencing to genetic diagnosis in multiplex families with idiopathic sensorineural hearing impairment.

Directory of Open Access Journals (Sweden)

Chen-Chi Wu

Full Text Available Despite the clinical utility of genetic diagnosis to address idiopathic sensorineural hearing impairment (SNHI, the current strategy for screening mutations via Sanger sequencing suffers from the limitation that only a limited number of DNA fragments associated with common deafness mutations can be genotyped. Consequently, a definitive genetic diagnosis cannot be achieved in many families with discernible family history. To investigate the diagnostic utility of massively parallel sequencing (MPS, we applied the MPS technique to 12 multiplex families with idiopathic SNHI in which common deafness mutations had previously been ruled out. NimbleGen sequence capture array was designed to target all protein coding sequences (CDSs and 100 bp of the flanking sequence of 80 common deafness genes. We performed MPS on the Illumina HiSeq2000, and applied BWA, SAMtools, Picard, GATK, Variant Tools, ANNOVAR, and IGV for bioinformatics analyses. Initial data filtering with allele frequencies (0.95 prioritized 5 indels (insertions/deletions and 36 missense variants in the 12 multiplex families. After further validation by Sanger sequencing, segregation pattern, and evolutionary conservation of amino acid residues, we identified 4 variants in 4 different genes, which might lead to SNHI in 4 families compatible with autosomal dominant inheritance. These included GJB2 p.R75Q, MYO7A p.T381M, KCNQ4 p.S680F, and MYH9 p.E1256K. Among them, KCNQ4 p.S680F and MYH9 p.E1256K were novel. In conclusion, MPS allows genetic diagnosis in multiplex families with idiopathic SNHI by detecting mutations in relatively uncommon deafness genes.

ADULT-ONSET STILL'S DISEASE: DIAGNOSIS AND TREATMENT

Directory of Open Access Journals (Sweden)

Rimma Mikhailovna Balabanova

2009-09-01

Full Text Available The paper describes adult-onset Still's disease (AOSD, a rare multisystemic disease of unknown etiology that is referred to as seronegative rheumatoid arthritis. It presents the major manifestations of AOSD: long-term fever, arthritis or persistent arthralgias, maculopapular eruption, seronegativity for rheumatoid factor, neutrophilic leukocytosis, and disease onset after 16 years of age, as well as additional signs: lymphadenopathy, hepatosplenomegaly, polyserositis, nasopharyngeal infection. It is noted that particular difficulties in the diagnosis of AOSD emerge when it is complicated by the hematophagocytic syndrome (HPS. The distinctive features of AOSD are the development of cutaneous and articular symptoms in practically 80% of patients and their absence in HPS. It is stated that of greater value in the diagnosis of HPS is examination of aspirate of the bone marrow than its biopsy. Most patients develop refractoriness to glucocorticoids and essential anti-inflammatory drugs. The positive results of using anakinra, rituximab, and tocilizumab are promising.

ADULT-ONSET STILL'S DISEASE: DIAGNOSIS AND TREATMENT

Directory of Open Access Journals (Sweden)

Rimma Mikhailovna Balabanova

2009-01-01

Full Text Available The paper describes adult-onset Still's disease (AOSD, a rare multisystemic disease of unknown etiology that is referred to as seronegative rheumatoid arthritis. It presents the major manifestations of AOSD: long-term fever, arthritis or persistent arthralgias, maculopapular eruption, seronegativity for rheumatoid factor, neutrophilic leukocytosis, and disease onset after 16 years of age, as well as additional signs: lymphadenopathy, hepatosplenomegaly, polyserositis, nasopharyngeal infection. It is noted that particular difficulties in the diagnosis of AOSD emerge when it is complicated by the hematophagocytic syndrome (HPS. The distinctive features of AOSD are the development of cutaneous and articular symptoms in practically 80% of patients and their absence in HPS. It is stated that of greater value in the diagnosis of HPS is examination of aspirate of the bone marrow than its biopsy. Most patients develop refractoriness to glucocorticoids and essential anti-inflammatory drugs. The positive results of using anakinra, rituximab, and tocilizumab are promising.

Computer tomography in the diagnosis of liver diseases

International Nuclear Information System (INIS)

Petkov, D.; Zhelyazkov, S.; Nedelkov, G.

1983-01-01

The modern achievements in the clinical study and diagnosis of liver diseases has definitely been associated with the application of whole body computer tomography (CT) in the practice. The diagnostic possibilities of the method come from high contrast and spacial disjunctive capabilities. Visualization of local lesions is associated with their size and the differences in their densitometric compactness from that of the normal parenchyma. The advantages of computer tomography in the diagnosis of liver diseases is discussed. They are associated with the possibilities for densitometric analysis of the pathologic changes, which opens a way for a probable qualitative diagnosis. Diffuse processes in the liver are relative indication for performing computer tomography. Examination under conditions of contrast amplification is indicated in cases when the nature of the lesion has to be specified and a ''negative'' result does not concur with the clinical manifestations. (authors)

Diagnosis of Parasitic Diseases: Old and New Approaches

Directory of Open Access Journals (Sweden)

Momar Ndao

2009-01-01

Full Text Available Methods for the diagnosis of infectious diseases have stagnated in the last 20–30 years. Few major advances in clinical diagnostic testing have been made since the introduction of PCR, although new technologies are being investigated. Many tests that form the backbone of the “modern” microbiology laboratory are based on very old and labour-intensive technologies such as microscopy for malaria. Pressing needs include more rapid tests without sacrificing sensitivity, value-added tests, and point-of-care tests for both high- and low-resource settings. In recent years, research has been focused on alternative methods to improve the diagnosis of parasitic diseases. These include immunoassays, molecular-based approaches, and proteomics using mass spectrometry platforms technology. This review summarizes the progress in new approaches in parasite diagnosis and discusses some of the merits and disadvantages of these tests.

Diagnostic accuracy of unenhanced, contrast-enhanced perfusion and angiographic MRI sequences for pulmonary embolism diagnosis: results of independent sequence readings

Energy Technology Data Exchange (ETDEWEB)

Revel, Marie Pierre [Hopital Europeen Georges Pompidou, APHP, Departments of Radiology, Paris (France); Universite Paris Descartes Sorbonne Paris Cite, Paris (France); Hotel-Dieu, Service de Radiologie, Paris (France); Sanchez, Olivier; Meyer, Guy [Hopital Europeen Georges Pompidou, APHP, Respiratory and intensive care and, Paris (France); Universite Paris Descartes Sorbonne Paris Cite, Paris (France); INSERM Unite 765, Paris (France); Lefort, Catherine; Couchon, Sophie; Hernigou, Anne; Frija, Guy [Hopital Europeen Georges Pompidou, APHP, Departments of Radiology, Paris (France); Niarra, Ralph [Hopital Europeen Georges Pompidou, APHP, Clinical Epidemiology, Paris (France); Universite Paris Descartes Sorbonne Paris Cite, Paris (France); Chatellier, Gilles [Hopital Europeen Georges Pompidou, APHP, Clinical Epidemiology, Paris (France); Universite Paris Descartes Sorbonne Paris Cite, Paris (France); INSERM CIC-EC E4, Paris (France)

2013-09-15

To independently evaluate unenhanced, contrast-enhanced perfusion and angiographic MR sequences for pulmonary embolism (PE) diagnosis. Prospective investigation, including 274 patients who underwent perfusion, unenhanced 2D steady-state-free-precession (SSFP) and contrast-enhanced 3D angiographic MR sequences on a 1.5-T unit, in addition to CTA (CT angiography). Two independent readers evaluated each sequence independently in random order. Sensitivity, specificity, predictive values and inter-reader agreement were calculated for each sequence, excluding sequences judged inconclusive. Sensitivity was also calculated according to PE location. Contrast-enhanced angiographic sequences showed the highest sensitivity (82.9 and 89.7 %, reader 1 and reader 2, respectively), specificity (98.5 and 100 %) and agreement (kappa value 0.77). Unenhanced angiographic sequences, although less sensitive overall (68.7 and 76.4 %), were sensitive for the detection of proximal PE (92.7 and 100 %) and showed high specificity (96.1 and 99.1 %) and good agreement (kappa value 0.62). Perfusion sequences showed lower sensitivity (75.0 and 79.3 %), specificity (84.8 and 89.7 %) and agreement (kappa value 0.51), and a negative predictive value of 84.8 % at best. Compared with contrast-enhanced angiographic sequences, unenhanced sequences demonstrate lower sensitivity, except for proximal PE, but high specificity and agreement. The negative predictive value of perfusion sequences was insufficient to safely rule out PE. (orig.)

Whole-Exome Sequencing in Adults With Chronic Kidney Disease: A Pilot Study.

Science.gov (United States)

Lata, Sneh; Marasa, Maddalena; Li, Yifu; Fasel, David A; Groopman, Emily; Jobanputra, Vaidehi; Rasouly, Hila; Mitrotti, Adele; Westland, Rik; Verbitsky, Miguel; Nestor, Jordan; Slater, Lindsey M; D'Agati, Vivette; Zaniew, Marcin; Materna-Kiryluk, Anna; Lugani, Francesca; Caridi, Gianluca; Rampoldi, Luca; Mattoo, Aditya; Newton, Chad A; Rao, Maya K; Radhakrishnan, Jai; Ahn, Wooin; Canetta, Pietro A; Bomback, Andrew S; Appel, Gerald B; Antignac, Corinne; Markowitz, Glen S; Garcia, Christine K; Kiryluk, Krzysztof; Sanna-Cherchi, Simone; Gharavi, Ali G

2018-01-16

The utility of whole-exome sequencing (WES) for the diagnosis and management of adult-onset constitutional disorders has not been adequately studied. Genetic diagnostics may be advantageous in adults with chronic kidney disease (CKD), in whom the cause of kidney failure often remains unknown. To study the diagnostic utility of WES in a selected referral population of adults with CKD. Observational cohort. A major academic medical center. 92 adults with CKD of unknown cause or familial nephropathy or hypertension. The diagnostic yield of WES and its potential effect on clinical management. Whole-exome sequencing provided a diagnosis in 22 of 92 patients (24%), including 9 probands with CKD of unknown cause and encompassing 13 distinct genetic disorders. Among these, loss-of-function mutations were identified in PARN in 2 probands with tubulointerstitial fibrosis. PARN mutations have been implicated in a short telomere syndrome characterized by lung, bone marrow, and liver fibrosis; these findings extend the phenotype of PARN mutations to renal fibrosis. In addition, review of the American College of Medical Genetics actionable genes identified a pathogenic BRCA2 mutation in a proband who was diagnosed with breast cancer on follow-up. The results affected clinical management in most identified cases, including initiation of targeted surveillance, familial screening to guide donor selection for transplantation, and changes in therapy. The small sample size and recruitment at a tertiary care academic center limit generalizability of findings among the broader CKD population. Whole-exome sequencing identified diagnostic mutations in a substantial number of adults with CKD of many causes. Further study of the utility of WES in the evaluation and care of patients with CKD in additional settings is warranted. New York State Empire Clinical Research Investigator Program, Renal Research Institute, and National Human Genome Research Institute of the National Institutes of

Role of fluorographic examinations in diagnosis of respiratory system diseases

International Nuclear Information System (INIS)

Vil'derman, A.M.; Tsurkan, E.P.; Moskovchuk, A.F.

1984-01-01

Materials are considered on the role of fluorography in diagnosis of posttuberculous changes and chromic respiratory system diseases during total epidemiologic examination of 7791 adults from urban and rural population. A scheme is developed that characterize diagnosed pathology of respiratory organs with references to medical establishments rendering medical supervision and forms of supervision. It is shown that fluorograhic examination of the population provide an early diagnosis of both tuberculosis, neoplastic diseases and nonspecific pulmonary diseases that have no visible clinical symptomatology

Differential diagnosis of genetic disease by DNA restriction fragment length polymorphisms

NARCIS (Netherlands)

Bolhuis, P. A.; Defesche, J. C.; van der Helm, H. J.

1987-01-01

DNA restriction fragment length polymorphisms (RFLPs) are used for diagnosis of genetic disease in families known to be affected by specific disorders, but RFLPs can be also useful for the differential diagnosis of hereditary disease. An RFLP pattern represents the inheritance of chromosomal markers

Forward chaining method on diagnosis of diseases and pests corn crop

Science.gov (United States)

Nurlaeli, Subiyanto

2017-03-01

Integrated pest management should be done to control the explosion of plants pest and diseases due to climate change is uncertain. This paper is a present implementation of the forward chaining method in the diagnosis diseases and pests of corn crop to help farmers/agricultural facilitators in getting knowledge about disease and pest corn crop. Forward chaining method as inference engine is used to get a disease/pest that attacks the corn crop based on symptoms. The forward chaining method works based on the fact that there is to get a conclusion. Fact in this system derived from the symptoms of the selected user is matched with the premise on every rule in the knowledge base. A rule that matches the facts to be executed to be the conclusion in the form of diagnosis. This validation using 36 data test, 32 data showed the same diagnostic results between systems with an expert. So, the percentage accuracy of results of diagnosis using data test of 88%. Finally, it can be concluded that the diagnosis system of diseases and pests corn crop can be used to help farmers/agricultural facilitators to diagnose diseases and pests corn crop.

Diagnostic dilemma: a young woman with Fabry disease symptoms, no family history, and a "sequencing cryptic" α-galactosidase a large deletion

DEFF Research Database (Denmark)

Feldt-Rasmussen, Ulla; Dobrovolny, Robert; Nazarenko, Irina

2011-01-01

Fabry disease, an X-linked lysosomal storage disorder, results from the deficient activity of a-galactosidase A (a-Gal A). In affected males, the clinical diagnosis is confirmed by the markedly decreased a-Gal A activity. However, in female heterozygotes, the a-Gal A activity can range from low t...... on enzyme replacement therapy. Thus, gene dosage analyses can detect large deletions (>50bp) in suspect heterozygotes for X-linked and autosomal dominant diseases that are "sequencing cryptic," resolving molecular diagnostic dilemmas....

Role of the biomarkers for the diagnosis of Creutzfeldt-Jakob disease.

Science.gov (United States)

Dulamea, A; Solomon, E

2016-01-01

Sporadic Creutzfeldt-Jakob disease (CJD) is a human prion disease, rapidly progressive and fatal, characterized by spongiform encephalopathy. The characteristic triad of signs - rapidly progressive dementia, myoclonus and periodic sharp wave complexes (PSWC) on electroencephalography (EEG) - usually appear in the late stages of the disease. The clinical diagnosis of CJD ante-mortem involves the exclusion of the rapidly progressive non-prionic dementias, the definitive diagnosis requiring brain tissue confirmation. Authors evaluated the methods of clinical diagnosis for sporadic CJD. This study retrospectively reviewed the medical records of patients diagnosed with probable sporadic CJD, based on brain magnetic resonance imaging (MRI), EEG, cerebrospinal fluid (CSF) analysis and extensive laboratory work-up. Four patients with a mean age of 67 years were included in our study. The mean duration from diagnosis until death was of 3.2 weeks. The clinical features of the disease at onset were atypical. In the final stage of the disease, all patients presented rapidly progressive dementia and myoclonus. High levels of 14-3-3 protein and tau protein and normal levels of amyloid β1-42 were found at CSF analysis, in all patients. PSWC on EEG were present in 3 out of 4 patients at different moments of the disease. MRI showed hyperintense lesions in brain cortex, caudate nucleus, and putamen on T2, FLAIR, and DWI. CJD may present various clinical features and, since brain biopsy is usually difficult to perform, a combination of biomarkers is useful in order to establish the diagnosis in the early phase of the disease.

The diagnosis of inflammatory muscular and vascular conditions using MRT with STIR sequences. Diagnostik entzuendlicher Muskel- und Gefaesserkrankungen in der MRT mit STIR-Sequenzen

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Beese, M.S. (Radiologische Klinik, Universitaetskrankenhaus Eppendorf, Hamburg (Germany)); Winkler, G. (Radiologische Klinik, Universitaetskrankenhaus Eppendorf, Hamburg (Germany) Neurologische Klinik, Universitaetskrankenhaus Eppendorf, Hamburg (Germany)); Nicolas, V. (Radiologische Klinik, Universitaetskrankenhaus Eppendorf, Hamburg (Germany)); Maas, R. (Radiologische Klinik, Universitaetskrankenhaus Eppendorf, Hamburg (Germany)); Kress, D. (Radiologische Klinik, Universitaetskrankenhaus Eppendorf, Hamburg (Germany)); Kunze, K. (Radiologische Klinik, Universitaetskrankenhaus Eppendorf, Hamburg (Germany) Neurologische Klinik, Universitaetskrankenhaus Eppendorf, Hamburg (Germany)); Buecheler, E. (Radiologische Klinik, Universitaetskrankenhaus Eppendorf, Hamburg (Germany))

1993-06-01

The role of MRT in the prebiopsy diagnosis of muscular and vascular inflammatory conditions was evaluated prospectively and an optimal method of examination was investigated. 92 patients with a suspected diagnosis of myositis (60 cases) or vasculitis (32 cases) were examined, in each case two extremities were studied using transverse T[sub 1] and T[sub 2] weighted SE sequences and double echo STIR sequences on a 0.5 Tesla (56 patients) or 1.5 Tesla magnet (36 patients; T5/S15 Gyroscan, Philips). The site of the biopsy depended on the MRT findings. In 41 patients the suspected diagnosis was confirmed histologically, in two patients an infective myositis was diagnosed on clinical grounds despite negative histology. MRT demonstrated muscle oedema in 86% of patients. There were negative findings after immuno-suppressive therapy (two patients), in focal myositis (3 out of 4 patients) and in one of 7 patients with untreated vasculitis. Amongst 49 patients in whom the suspected diagnosis could not be confirmed there was muscle oedema in 11 cases (9 neuropathies out of 22, two myopathies out of 10). Oedema indicated inflammatory muscular or vascular disease with a sensitivity of 97% (except in treated patients and for focal myositis). The number of false negative biopsies can be greatly reduced by the use of MRT. (orig.)

Epstein-Barr Virus Sequence Variation—Biology and Disease

Science.gov (United States)

Tzellos, Stelios; Farrell, Paul J.

2012-01-01

Some key questions in Epstein-Barr virus (EBV) biology center on whether naturally occurring sequence differences in the virus affect infection or EBV associated diseases. Understanding the pattern of EBV sequence variation is also important for possible development of EBV vaccines. At present EBV isolates worldwide can be grouped into Type 1 and Type 2, a classification based on the EBNA2 gene sequence. Type 1 EBV is the most prevalent worldwide but Type 2 is common in parts of Africa. Type 1 transforms human B cells into lymphoblastoid cell lines much more efficiently than Type 2 EBV. Molecular mechanisms that may account for this difference in cell transformation are now becoming clearer. Advances in sequencing technology will greatly increase the amount of whole EBV genome data for EBV isolated from different parts of the world. Study of regional variation of EBV strains independent of the Type 1/Type 2 classification and systematic investigation of the relationship between viral strains, infection and disease will become possible. The recent discovery that specific mutation of the EBV EBNA3B gene may be linked to development of diffuse large B cell lymphoma illustrates the importance that mutations in the virus genome may have in infection and human disease. PMID:25436768

Genetic diagnosis of Duchenne and Becker muscular dystrophy using next-generation sequencing technology: comprehensive mutational search in a single platform.

Science.gov (United States)

Lim, Byung Chan; Lee, Seungbok; Shin, Jong-Yeon; Kim, Jong-Il; Hwang, Hee; Kim, Ki Joong; Hwang, Yong Seung; Seo, Jeong-Sun; Chae, Jong Hee

2011-11-01

Duchenne muscular dystrophy or Becker muscular dystrophy might be a suitable candidate disease for application of next-generation sequencing in the genetic diagnosis because the complex mutational spectrum and the large size of the dystrophin gene require two or more analytical methods and have a high cost. The authors tested whether large deletions/duplications or small mutations, such as point mutations or short insertions/deletions of the dystrophin gene, could be predicted accurately in a single platform using next-generation sequencing technology. A custom solution-based target enrichment kit was designed to capture whole genomic regions of the dystrophin gene and other muscular-dystrophy-related genes. A multiplexing strategy, wherein four differently bar-coded samples were captured and sequenced together in a single lane of the Illumina Genome Analyser, was applied. The study subjects were 25 16 with deficient dystrophin expression without a large deletion/duplication and 9 with a known large deletion/duplication. Nearly 100% of the exonic region of the dystrophin gene was covered by at least eight reads with a mean read depth of 107. Pathogenic small mutations were identified in 15 of the 16 patients without a large deletion/duplication. Using these 16 patients as the standard, the authors' method accurately predicted the deleted or duplicated exons in the 9 patients with known mutations. Inclusion of non-coding regions and paired-end sequence analysis enabled accurate identification by increasing the read depth and providing information about the breakpoint junction. The current method has an advantage for the genetic diagnosis of Duchenne muscular dystrophy and Becker muscular dystrophy wherein a comprehensive mutational search may be feasible using a single platform.

Exome Sequencing and the Management of Neurometabolic Disorders.

Science.gov (United States)

Tarailo-Graovac, Maja; Shyr, Casper; Ross, Colin J; Horvath, Gabriella A; Salvarinova, Ramona; Ye, Xin C; Zhang, Lin-Hua; Bhavsar, Amit P; Lee, Jessica J Y; Drögemöller, Britt I; Abdelsayed, Mena; Alfadhel, Majid; Armstrong, Linlea; Baumgartner, Matthias R; Burda, Patricie; Connolly, Mary B; Cameron, Jessie; Demos, Michelle; Dewan, Tammie; Dionne, Janis; Evans, A Mark; Friedman, Jan M; Garber, Ian; Lewis, Suzanne; Ling, Jiqiang; Mandal, Rupasri; Mattman, Andre; McKinnon, Margaret; Michoulas, Aspasia; Metzger, Daniel; Ogunbayo, Oluseye A; Rakic, Bojana; Rozmus, Jacob; Ruben, Peter; Sayson, Bryan; Santra, Saikat; Schultz, Kirk R; Selby, Kathryn; Shekel, Paul; Sirrs, Sandra; Skrypnyk, Cristina; Superti-Furga, Andrea; Turvey, Stuart E; Van Allen, Margot I; Wishart, David; Wu, Jiang; Wu, John; Zafeiriou, Dimitrios; Kluijtmans, Leo; Wevers, Ron A; Eydoux, Patrice; Lehman, Anna M; Vallance, Hilary; Stockler-Ipsiroglu, Sylvia; Sinclair, Graham; Wasserman, Wyeth W; van Karnebeek, Clara D

2016-06-09

Whole-exome sequencing has transformed gene discovery and diagnosis in rare diseases. Translation into disease-modifying treatments is challenging, particularly for intellectual developmental disorder. However, the exception is inborn errors of metabolism, since many of these disorders are responsive to therapy that targets pathophysiological features at the molecular or cellular level. To uncover the genetic basis of potentially treatable inborn errors of metabolism, we combined deep clinical phenotyping (the comprehensive characterization of the discrete components of a patient's clinical and biochemical phenotype) with whole-exome sequencing analysis through a semiautomated bioinformatics pipeline in consecutively enrolled patients with intellectual developmental disorder and unexplained metabolic phenotypes. We performed whole-exome sequencing on samples obtained from 47 probands. Of these patients, 6 were excluded, including 1 who withdrew from the study. The remaining 41 probands had been born to predominantly nonconsanguineous parents of European descent. In 37 probands, we identified variants in 2 genes newly implicated in disease, 9 candidate genes, 22 known genes with newly identified phenotypes, and 9 genes with expected phenotypes; in most of the genes, the variants were classified as either pathogenic or probably pathogenic. Complex phenotypes of patients in five families were explained by coexisting monogenic conditions. We obtained a diagnosis in 28 of 41 probands (68%) who were evaluated. A test of a targeted intervention was performed in 18 patients (44%). Deep phenotyping and whole-exome sequencing in 41 probands with intellectual developmental disorder and unexplained metabolic abnormalities led to a diagnosis in 68%, the identification of 11 candidate genes newly implicated in neurometabolic disease, and a change in treatment beyond genetic counseling in 44%. (Funded by BC Children's Hospital Foundation and others.).

Heart Health - Heart Disease: Symptoms, Diagnosis, Treatment

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... Bar Home Current Issue Past Issues Cover Story Heart Health Heart Disease: Symptoms, Diagnosis, Treatment Past Issues / Winter 2009 ... of this page please turn Javascript on. Most heart attacks happen when a clot in the coronary ...

Cytauxzoonosis: Diagnosis and treatment of an emerging disease.

Science.gov (United States)

Sherrill, Meredith K; Cohn, Leah A

2015-11-01

Cytauxzoonosis is a life-threatening hematoprotozoal disease with a rapidly progressive clinical course. Once considered a rare disease only relevant to a small geographic area, it is now recognized in more than about a third of the United States. The geographic range seems likely to increase with expansion of the range of the vector tick. Both disease diagnosis and treatment offer challenges. The acute illness is often recognized by characteristic parasitic cellular inclusions, but illness may occur before parasites can be identified, and parasitic inclusions may persist long after illness has resolved. Also, while infection was once considered nearly uniformly fatal, subclinical infections are now recognized. Disease prognosis has improved for many cats through implementation of new therapies, but some pathogens are resistant to these therapies and death from disease is still common. Currently, prevention strategies are limited to ectoparasite control. Cytauxzoonosis caused by Cytauxzoon felis is limited to the Americas, and is especially problematic in southeastern and south central USA. However, other Cytauxzoon species have been recognized in Europe and Asia. This review is aimed at veterinary practitioners and focuses on the diagnosis and treatment of cytauxzoonosis. Disease management is of crucial importance in endemic regions. Furthermore, the expanding geographic range of infection, and the possibility of parasite identification in chronically infected cats with a travel history, make understanding cytauxzoonosis relevant in non-endemic regions as well. The authors draw on evidence from prospective clinical trials, experimental infections, retrospective clinical studies and case reports, as well as their own personal experience with the diagnosis and treatment of cytauxzoonosis. © The Author(s) 2015.

Targeted gene panel sequencing in children with very early onset inflammatory bowel disease--evaluation and prospective analysis.

Science.gov (United States)

Kammermeier, Jochen; Drury, Suzanne; James, Chela T; Dziubak, Robert; Ocaka, Louise; Elawad, Mamoun; Beales, Philip; Lench, Nicholas; Uhlig, Holm H; Bacchelli, Chiara; Shah, Neil

2014-11-01

Multiple monogenetic conditions with partially overlapping phenotypes can present with inflammatory bowel disease (IBD)-like intestinal inflammation. With novel genotype-specific therapies emerging, establishing a molecular diagnosis is becoming increasingly important. We have introduced targeted next-generation sequencing (NGS) technology as a prospective screening tool in children with very early onset IBD (VEOIBD). We evaluated the coverage of 40 VEOIBD genes in two separate cohorts undergoing targeted gene panel sequencing (TGPS) (n=25) and whole exome sequencing (WES) (n=20). TGPS revealed causative mutations in four genes (IL10RA, EPCAM, TTC37 and SKIV2L) discovered unexpected phenotypes and directly influenced clinical decision making by supporting as well as avoiding haematopoietic stem cell transplantation. TGPS resulted in significantly higher median coverage when compared with WES, fewer coverage deficiencies and improved variant detection across established VEOIBD genes. Excluding or confirming known VEOIBD genotypes should be considered early in the disease course in all cases of therapy-refractory VEOIBD, as it can have a direct impact on patient management. To combine both described NGS technologies would compensate for the limitations of WES for disease-specific application while offering the opportunity for novel gene discovery in the research setting. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Continuation of lithium after a diagnosis of chronic kidney disease

DEFF Research Database (Denmark)

Kessing, L V; Feldt-Rasmussen, B; Andersen, P K

2017-01-01

OBJECTIVE: To investigate whether continued lithium or anticonvulsant treatment after a first diagnosis of chronic kidney disease (CKD) was associated with progression to irreversible end-stage kidney disease. METHODS: Nationwide cohort study including all individuals in Denmark in a period from...... 1995 to 2012 with a diagnosis of CKD and (i) a history of lithium treatment (N = 754, among whom 238 patients had a diagnosis of bipolar disorder) or (ii) a history of anticonvulsant treatment (N = 5.004, among whom 199 patients had a diagnosis of bipolar disorder). End-stage CKD was defined as chronic...... dialysis or renal transplantation. RESULTS: Continuing lithium (HR = 0.58 (95% CI: 0.37-0.90) and continuing anticonvulsants (HR = 0.53 (95% CI: 0.44-0.64) were associated with decreased rates of end-stage CKD. In the subcohorts of patients with a diagnosis of bipolar disorder, continuing lithium...

Hyper-connectivity of functional networks for brain disease diagnosis.

Science.gov (United States)

Jie, Biao; Wee, Chong-Yaw; Shen, Dinggang; Zhang, Daoqiang

2016-08-01

Exploring structural and functional interactions among various brain regions enables better understanding of pathological underpinnings of neurological disorders. Brain connectivity network, as a simplified representation of those structural and functional interactions, has been widely used for diagnosis and classification of neurodegenerative diseases, especially for Alzheimer's disease (AD) and its early stage - mild cognitive impairment (MCI). However, the conventional functional connectivity network is usually constructed based on the pairwise correlation among different brain regions and thus ignores their higher-order relationships. Such loss of high-order information could be important for disease diagnosis, since neurologically a brain region predominantly interacts with more than one other brain regions. Accordingly, in this paper, we propose a novel framework for estimating the hyper-connectivity network of brain functions and then use this hyper-network for brain disease diagnosis. Here, the functional connectivity hyper-network denotes a network where each of its edges representing the interactions among multiple brain regions (i.e., an edge can connect with more than two brain regions), which can be naturally represented by a hyper-graph. Specifically, we first construct connectivity hyper-networks from the resting-state fMRI (R-fMRI) time series by using sparse representation. Then, we extract three sets of brain-region specific features from the connectivity hyper-networks, and further exploit a manifold regularized multi-task feature selection method to jointly select the most discriminative features. Finally, we use multi-kernel support vector machine (SVM) for classification. The experimental results on both MCI dataset and attention deficit hyperactivity disorder (ADHD) dataset demonstrate that, compared with the conventional connectivity network-based methods, the proposed method can not only improve the classification performance, but also help

Identification of A Novel Missense Mutation in The Norrie Disease Gene: The First Molecular Genetic Analysis and Prenatal Diagnosis of Norrie Disease in An Iranian Family.

Science.gov (United States)

Talebi, Farah; Ghanbari Mardasi, Farideh; Mohammadi Asl, Javad; Lashgari, Ali; Farhadi, Freidoon

2018-07-01

Norrie disease (ND) is a rare X-linked recessive disorder, which is characterized by congenital blindness and, in several cases, accompanied with mental retardation and deafness. ND is caused by mutations in NDP, located on the proximal short arm of the X chromosome (Xp11.3). The disease has been observed in many ethnic groups worldwide, however, no such case has been reported from Iran. In this study, we present the molecular analysis of two patients with ND and the subsequent prenatal diagnosis. Screening of NDP identified a hemizygous missense mutation (p.Ser133Cys) in the affected male siblings of the family. The mother was the carrier for the mutation (p.Ser133Cys). In a subsequent chorionic amniotic pregnancy, we carried out prenatal diagnosis by sequencing NDP in the chorionic villi sample at 11 weeks of gestation. The fetus was carrying the mutation and thus unaffected. This is the first mutation report and prenatal diagnosis of an Iranian family with ND, and highlights the importance of prenatal diagnostic screening of this congenital disorder and relevant genetic counseling. Copyright© by Royan Institute. All rights reserved.

Chronic obstructive pulmonary disease – diagnosis and ...

African Journals Online (AJOL)

Chronic obstructive pulmonary disease – diagnosis and classification of ... biomass fuel exposure/household pollution, tuberculosis, HIV and mining ... There is a very high prevalence of COPD in SA and it is the third leading cause of mortality ...

The value of MRI in the diagnosis of heart valve diseases

International Nuclear Information System (INIS)

Zhao Shihua; Lu Minjie; Zhang Yan; Jiang Shiliang; Liu Yuqing; Zhang Puhong

2006-01-01

Objective: To assess the diagnostic value of the magnetic resonance imaging (MRI) for heart valve disease qualitatively and quantitatively. Methods: From 18th Sep, 2004 to 30th Jun, 2005, 56 consecutive patients underwent MR scanning with multiple sequences, including two-dimensional dark and bright sequences, K-space segmented TrueFISP and FLASH cine sequences, as well as velocity-encoded cine MR(VEC-MR). Morphologic and functional parameters were applied to assess the disease qualitatively and quantitatively. For quantitative analysis, Doppler echocardiography was compared to evaluate the reliability of VEC-MR in assessing the severity of aortic valve disease. Correlations coefficient was analyzed by a statistic software (SPSS 13.0), P sq =0.951, P=0.01 for AS and R=0.965, R sq =0.932, P<0.01 for AI). Conclusion: Heart valve diseases can be qualitatively and quantitatively evaluated by MR multiple sequences, especially in aortic valve disease. (authors)

DNA technology for diagnosis and vaccines for infectious diseases

International Nuclear Information System (INIS)

Notani, N.K.

1992-01-01

Three or four general strategies are adopted for the control of infectious diseases. Early diagnosis, vaccination and chemotherapy. In the situations where there is transfer through mosquitoes or ticks from alternate hosts, control of the vector and of the infection in the alternate host are additional measures to be taken. This Chapter looks at the problems of disease control from the perspective of genetics, since molecular genetics now provides powerful tools in the form of radiolabelled DNA probes and clones of selected segments, useful for diagnosis as well as for vaccine design

DNA technology for diagnosis and vaccines for infectious diseases

Energy Technology Data Exchange (ETDEWEB)

Notani, N K

1993-12-31

Three or four general strategies are adopted for the control of infectious diseases. Early diagnosis, vaccination and chemotherapy. In the situations where there is transfer through mosquitoes or ticks from alternate hosts, control of the vector and of the infection in the alternate host are additional measures to be taken. This Chapter looks at the problems of disease control from the perspective of genetics, since molecular genetics now provides powerful tools in the form of radiolabelled DNA probes and clones of selected segments, useful for diagnosis as well as for vaccine design

FLAIR MR sequence in the diagnosis and follow-up of low-grade astrocytomas

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Stošić-Opinćal Tatjana

2005-01-01

Full Text Available Aim. To evaluate the sensitivity of fluid-attenuated inversion recovery (FLAIR sequence in the diagnosis and follow-up of the patients with low-grade astrocytomas compared with T2-weighted (T2W sequence. Methods. Twenty-four patients with biopsy- confirmed low-grade astrocytoma (age range, 15-66 years underwent T1- weighted (T1W, T2W and FLAIR imaging with a superconducting unit 1.0 T. FLAIR images were qualitatively evaluated by comparison with T2W images by the three experienced neuroradiologists. To evaluate the diagnostic value of FLAIR, the neuroradiologists individually assessed the possibilities of the detection of lesions, as well as the possibilities of the differentiation of tumor from the surrounding edema on FLAIR vs. T2W images. Every examiner ranked FLAIR sequence vs. T2W in three degrees: worse, equal and better. Results. The comparison of FLAIR with T2W spin-echo (SE images with regard to the detection of the lesions showed that 82.8% of FLAIR studies were superior, 17.2% were of similar diagnostic value, and none was inferior to the T2W images. The comparison of images with regard to the differentiation of tumor boundaries vs. surrounding edema showed that 92.5% of FLAIR studies were superior, 7.5% were of similar diagnostic value, and none was inferior to the T2W images. Conclusion. Our results were similar to the previous studies' results concerning the advantages of FLAIR sequence in the diagnosis of low grade astrocytomas over T2W sequence. FLAIR was better at showing different tumor components, and at distinguishing CSF from the cystic component, and the postoperative cavity, compared with T2W images. Our conclusion was that FLAIR could be routinely used in the evaluation and follow-up of low-grade astrocytomas.

Diagnosis of Periodontal Diseases by Biomarkers

Science.gov (United States)

Kido, Jun-Ichi; Hino, Mami; Bando, Mika; Hiroshima, Yuka

Many middle aged and old persons take periodontal diseases that mainly cause teeth loss and result in some systemic diseases. The prevention of periodontal diseases is very important for oral and systemic health, but the present diagnostic examination is not fully objective and suitable. To diagnose periodontal diseases exactly, some biomarkers shown inflammation, tissue degradation and bone resorption, in gingival crevicular fluid (GCF) and saliva are known. We demonstrated that GCF levels of calprotectin, inflammation-related protein, and carboxy-terminal propeptide of type I procollagen, bone metabolism-related protein, were associated with clinical condition of periodontal diseases, and suggested that these proteins may be useful biomarkers for periodontal diseases. Recently, determinations of genes and proteins by using microdevices are studied for diagnosis of some diseases. We detected calprotectin protein by chemiluminescent immunoassay on a microchip and showed the possibility of specific and quantitative detection of calprotectin in a very small amount of GCF. To determine plural markers in GCF by using microdevices contributes to develop accurate, objective diagnostic system of periodontal diseases.

Landmark-based deep multi-instance learning for brain disease diagnosis.

Science.gov (United States)

Liu, Mingxia; Zhang, Jun; Adeli, Ehsan; Shen, Dinggang

2018-01-01

In conventional Magnetic Resonance (MR) image based methods, two stages are often involved to capture brain structural information for disease diagnosis, i.e., 1) manually partitioning each MR image into a number of regions-of-interest (ROIs), and 2) extracting pre-defined features from each ROI for diagnosis with a certain classifier. However, these pre-defined features often limit the performance of the diagnosis, due to challenges in 1) defining the ROIs and 2) extracting effective disease-related features. In this paper, we propose a landmark-based deep multi-instance learning (LDMIL) framework for brain disease diagnosis. Specifically, we first adopt a data-driven learning approach to discover disease-related anatomical landmarks in the brain MR images, along with their nearby image patches. Then, our LDMIL framework learns an end-to-end MR image classifier for capturing both the local structural information conveyed by image patches located by landmarks and the global structural information derived from all detected landmarks. We have evaluated our proposed framework on 1526 subjects from three public datasets (i.e., ADNI-1, ADNI-2, and MIRIAD), and the experimental results show that our framework can achieve superior performance over state-of-the-art approaches. Copyright © 2017 Elsevier B.V. All rights reserved.

Delay in Diagnosis of Celiac Disease in Patients Without Gastrointestinal Complaints.

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Paez, Marco A; Gramelspacher, Anna Maria; Sinacore, James; Winterfield, Laura; Venu, Mukund

2017-11-01

The purpose of our study is to investigate the delay in diagnosis of patients with biopsy-proven celiac disease in those who present with gastrointestinal complaints vs nongastrointestinal complaints at our tertiary care center. Celiac disease is an autoimmune disorder that affects approximately 1% of the population worldwide. Celiac disease can have variable clinical presentations; it can be characterized by predominately gastrointestinal symptoms, or it may present without any gastrointestinal symptoms. We retrospectively reviewed the charts of 687 adult patients who carried the diagnosis of celiac disease. Patients included had biopsy-proven celiac disease and were categorized based on presence or absence of gastrointestinal symptoms prior to their diagnosis. There were 101 patients with biopsy-proven celiac disease that met inclusion criteria. Fifty-two patients presented with gastrointestinal symptoms and 49 had nongastrointestinal complaints. Results from Mann-Whitney statistical analysis showed a median delay in diagnosis of 2.3 months for the gastrointestinal symptoms group and 42 months for the nongastrointestinal group (P symptoms had abnormal thyroid-stimulating hormone, as opposed to 15.5% in the gastrointestinal symptom group (P = .004). Of patients with nongastrointestinal symptoms, 69.4% had anemia, compared with 11.5% of the gastrointestinal symptom group (P symptom group, 68%, were noted to have abnormal bone density scans, compared with 41% in the gastrointestinal symptom group. No sex differences were noted on chi-squared analysis between the 2 groups (P = .997). Although there is growing awareness of celiac disease, the delay in diagnosis for patients without gastrointestinal symptoms remains prolonged, with an average delay of 3.5 years. Copyright © 2017 Elsevier Inc. All rights reserved.

Pulmonary nuclear medicine: Techniques in diagnosis of lung disease

International Nuclear Information System (INIS)

Atkins, H.L.

1984-01-01

This book presents papers on the application of nuclear medicine to the diagnosis of lung diseases. Topics considered include lung physiology and anatomy, radiopharmaceuticals in pulmonary medicine, pulmonary embolism, obstructive pulmonary disease, diffuse infiltrative lung disease, pneumoconioses, tumor localization scans in primary lung tumors, the interactions of heart diseases and lung diseases on radionuclide tests of lung anatomy and function, radionuclide imaging in pediatric lung diseases, and future possibilities in pulmonary nuclear medicine

Prion diseases of the brain

International Nuclear Information System (INIS)

Lutz, Kira; Urbach, Horst

2015-01-01

The prion diseases of the brain, especially Creutzfeldt-Jakob disease, are rare fatal neurodegenerative disorders. A definitive CJD diagnosis is currently only possible by a brain biopsy or post mortem autopsy. The diagnosis of Creutzfeldt-Jakob disease is based on clinical signs, pathognomonic EEG, on typical MRI findings and the examination of the cerebrospinal fluid. Using the MRI the diagnosis Creutzfeldt-Jakob disease can be confirmed or excluded with high certainty. The MRI examination should contain diffusion-weighted and FLAIR imaging sequences. This review article provides an overview of the prion diseases of the brain with the corresponding imaging findings.

Research of Litchi Diseases Diagnosis Expertsystem Based on Rbr and Cbr

Science.gov (United States)

Xu, Bing; Liu, Liqun

To conquer the bottleneck problems existing in the traditional rule-based reasoning diseases diagnosis system, such as low reasoning efficiency and lack of flexibility, etc.. It researched the integrated case-based reasoning (CBR) and rule-based reasoning (RBR) technology, and put forward a litchi diseases diagnosis expert system (LDDES) with integrated reasoning method. The method use data mining and knowledge obtaining technology to establish knowledge base and case library. It adopt rules to instruct the retrieval and matching for CBR, and use association rule and decision trees algorithm to calculate case similarity.The experiment shows that the method can increase the system's flexibility and reasoning ability, and improve the accuracy of litchi diseases diagnosis.

The importance of genetics in the diagnosis of animal diseases - A ...

African Journals Online (AJOL)

STORAGESEVER

2010-01-25

Jan 25, 2010 ... Veterinary and genetic research has been successfully used in diagnosis and ... pathogen sequencing programmes in which scientists are ..... Selectively nonselective drugs for mood disorders and schizophrenia. Nature Rev ...

Application of Metabonomics in Early Diagnosis of Diseases

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Qiao LIU

2015-06-01

Full Text Available With the development of life sciences, people have changed their focus from local research to systematic biology, thus contributing to the development of a series of “omics”, including genomics, transcriptomics, proteomics and metabonomics, etc. Metabonomics is a presently developed new branch of science that can provide qualitative and quantitative analysis on all metabolites with low-molecular quality in the body, tissues or cells of an organism. It recognizes the changes and rules of the biological endogenous substance under the impact of internal and external factors by generally and quantitatively detecting multiple small molecular compounds in biological samples, in hope of finding out the metabolic marker clusters in the early stage of diseases so as to provide new pathways for the early diagnosis of the diseases and the realization of individualized drug administration. Additionally, metabonomics research on clinical diseases has become a hot topic and made great achievement in the developmental condition, diagnostic methods, pathogenic mechanism and pharmaceutical efficacy evaluation of diseases. This study mainly reviewed the application and advances of metabonomics in the early diagnosis of malignant tumors, cardiovascular and respiratory diseases, hoping to provide references and prompts for metabonomics-associated researches.

Exploring Symmetry to Assist Alzheimer's Disease Diagnosis

Science.gov (United States)

Illán, I. A.; Górriz, J. M.; Ramírez, J.; Salas-Gonzalez, D.; López, M.; Padilla, P.; Chaves, R.; Segovia, F.; Puntonet, C. G.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder first affecting memory functions and then gradually affecting all cognitive functions with behavioral impairments and eventually causing death. Functional brain imaging as Single-Photon Emission Computed Tomography (SPECT) is commonly used to guide the clinician's diagnosis. The essential left-right symmetry of human brains is shown to play a key role in coding and recognition. In the present work we explore the implications of this symmetry in AD diagnosis, showing that recognition may be enhanced when considering this latent symmetry.

Cataplexy leading to the diagnosis of Niemann-Pick disease type C.

Science.gov (United States)

Smit, Liesbeth S; Lammers, Gert Jan; Catsman-Berrevoets, Coriene E

2006-07-01

Cataplexy in childhood is a rare and often misdiagnosed symptom. It is described as a brief episode of bilateral loss of muscle tone with intact consciousness, triggered by a variety of strong emotions and in particular with unexpected laughter. This report presents a 9-year old male with progressive cerebellar and pyramidal symptoms and a cognitive decline since the age of 4. His recently developed "drop attacks" on laughter were recognized as cataplexy and led to the diagnosis of Niemann-Pick type C disease. With biochemical studies this diagnosis, a lysosomal storage disease, was confirmed. With cataplexy narcolepsy, Niemann-Pick type C disease, Norrie disease, Prader-Willi syndrome, and Coffin-Lowry syndrome are associated disorders. Recognition of cataplexy in children with concomitant neurologic symptoms may lead to an early and straight diagnosis of one of these disorders.

New Features of Disease after Diagnosis in Six Forms of Systemic Vasculitis

Science.gov (United States)

Grayson, Peter C.; Cuthbertson, David; Carette, Simon; Hoffman, Gary S.; Khalidi, Nader A.; Koening, Curry L.; Langford, Carol A.; Maksimowicz-McKinnon, Kathleen; Monach, Paul A.; Seo, Philip; Specks, Ulrich; Ytterberg, Steven R.; Merkel, Peter A.

2015-01-01

Objective To quantify the occurrence of features of vasculitis that initially present after diagnosis in 6 types of primary vasculitis. Methods Standardized collection of data on 95 disease manifestations in 6 vasculitides, including granulomatosis with polyangiitis (Wegener's, GPA), microscopic polyangiitis (MPA), eosinophilic granulomatosis with polyangiitis (Churg-Strauss, EGPA), polyarteritis nodosa (PAN), giant cell arteritis (GCA), and Takayasu's arteritis (TAK), was performed within a set of multicenter longitudinal, observational cohorts. For each form of vasculitis, the frequency of disease-specific manifestations at diagnosis was compared to the cumulative frequency of each manifestation. The percentage of patients who initially developed “severe” manifestations after diagnosis, defined as organ- or life-threatening in the small and medium vessel vasculitides (GPA, MPA, EGPA, PAN) and as ischemic/vascular in the large vessel vasculitides (GCA, TAK), was reported. Results Out of 838 patients with vasculitis, 490 (59%) experienced ≥ 1 new disease manifestation after diagnosis. On average, patients with vasculitis experienced 1.3 new manifestations after diagnosis (GPA - 1.9, MPA - 1.2, EGPA - 1.5, PAN - 1.2, GCA - 0.7, TAK - 1.0). New severe manifestations occurred after diagnosis in 224 (27%) out of 838 patients (GPA - 26%, MPA - 19%, EGPA - 21%, PAN - 23%, GCA - 24%, and TAK - 44%). Timing of onset of new manifestations was not significantly associated with disease duration. Conclusion A majority of patients with vasculitis develop new disease features after diagnosis, including a substantial number of new, severe manifestations. Ongoing assessment of patients with established vasculitis should remain broad in scope. PMID:23908447

In-utero diagnosis of Norrie disease by ultrasonography.

Science.gov (United States)

Redmond, R M; Vaughan, J I; Jay, M; Jay, B

1993-03-01

Obstetric ultrasonography of an obligate Norrie disease carrier revealed bilateral retinal detachments in a third trimester male fetus. Postnatal examination confirmed the diagnosis of Norrie disease. DNA linkage analysis with the markers L1.28 and MAO had been uninformative for this family. This report suggests that retinal detachment occurs late in the gestation of the affected fetus.

Prevalence of metabolic bone disease in children with celiac disease is independent of symptoms at diagnosis.

Science.gov (United States)

Turner, Justine; Pellerin, Genevieve; Mager, Diana

2009-11-01

: Given dietary gluten exposure, growing children with celiac disease may experience malabsorption of nutrients, negatively affecting bone health. The purpose of this study was to determine the prevalence of low bone mass in children with celiac disease, according to the presence of symptoms at diagnosis. : A retrospective chart review of the Stollery Children's Hospital Celiac Clinic charts (April 1989-September 2007) was conducted. Bone mineral density (BMD) of the spine was measured using dual energy x-ray absorptiometry. Demographics, symptoms at presentation, and anthropometric and biochemical data relevant to bone health were recorded. : Seventy-four children (9.6 +/- 3.7 years; range 3.3-16.0 years) were included. Lumbar BMD z scores more than or equal to -1 were observed in 58 cases (65%), z scores below -1 but above -2 were observed in 14 cases (19%) and z scores less than or equal to -2 were observed in 12 cases (16%). There was no significant difference in mean lumbar BMD z scores between symptomatic and asymptomatic children (P = 0.34). When adjusted for bone age and bone surface area, BMD lumbar z score was inversely correlated with age at diagnosis (P celiac disease at diagnosis regardless of the presence of symptoms. Delayed diagnosis of children with celiac disease may increase the risk of adult osteoporosis. Appropriate screening of children at risk of celiac disease for the purpose of early diagnosis, as well as routine evaluation of bone mineral density in such children, are important to prevent long-term complications associated with poor bone health.

Advances in Raman spectroscopy for the diagnosis of Alzheimer's disease

Science.gov (United States)

Sudworth, Caroline D.; Archer, John K. J.; Black, Richard A.; Mann, David

2006-02-01

Within the next 50 years Alzheimer's disease is expected to affect 100 million people worldwide. The progressive decline in the mental health of the patient is caused by severe brain atrophy generated by the breakdown and aggregation of proteins, resulting in β-amyloid plaques and neurofibrillary tangles. The greatest challenge to Alzheimer's disease lies in the pursuit of an early and definitive diagnosis, in order that suitable treatment can be administered. At the present time, definitive diagnosis is restricted to post-mortem examination. Alzheimer's disease also remains without a long-term cure. This research demonstrates the potential role of Raman spectroscopy, combined with principle components analysis (PCA), as a diagnostic method. Analyses of ethically approved ex vivo post-mortem brain tissues (originating from frontal and occipital lobes) from control (3 normal elderly subjects and 3 Huntingdon's disease subjects) and Alzheimer's disease (12 subjects) brain sections, and a further set of 12 blinded samples are presented. Spectra originating from these tissues are highly reproducible, and initial results indicate a vital difference in protein content and conformation, relating to the abnormally high levels of aggregated proteins in the diseased tissues. Further examination of these spectra using PCA allows for the separation of control from diseased tissues. The validation of the PCA models using blinded samples also displays promise for the identification of Alzheimer's disease, in conjunction with secondary information regarding other brain diseases and dementias. These results provide a route for Raman spectroscopy as a possible non-invasive, non-destructive tool for the early diagnosis of Alzheimer's disease.

Diagnostic exome sequencing provides a molecular diagnosis for a significant proportion of patients with epilepsy.

Science.gov (United States)

Helbig, Katherine L; Farwell Hagman, Kelly D; Shinde, Deepali N; Mroske, Cameron; Powis, Zöe; Li, Shuwei; Tang, Sha; Helbig, Ingo

2016-09-01

To assess the yield of diagnostic exome sequencing (DES) and to characterize the molecular findings in characterized and novel disease genes in patients with epilepsy. In an unselected sample of 1,131 patients referred for DES, overall results were compared between patients with and without epilepsy. DES results were examined based on age of onset and epilepsy diagnosis. Positive/likely positive results were identified in 112/293 (38.2%) epilepsy patients compared with 210/732 (28.7%) patients without epilepsy (P = 0.004). The diagnostic yield in characterized disease genes among patients with epilepsy was 33.4% (105/314). KCNQ2, MECP2, FOXG1, IQSEC2, KMT2A, and STXBP1 were most commonly affected by de novo alterations. Patients with epileptic encephalopathies had the highest rate of positive findings (43.4%). A likely positive novel genetic etiology was proposed in 14/200 (7%) patients with epilepsy; this frequency was highest in patients with epileptic encephalopathies (17%). Three genes (COQ4, DNM1, and PURA) were initially reported as likely positive novel disease genes and were subsequently corroborated in independent peer-reviewed publications. DES with analysis and interpretation of both characterized and novel genetic etiologies is a useful diagnostic tool in epilepsy, particularly in severe early-onset epilepsy. The reporting on novel genetic etiologies may further increase the diagnostic yield.Genet Med 18 9, 898-905.

Medical microbiology: laboratory diagnosis of invasive pneumococcal disease.

Science.gov (United States)

Werno, Anja M; Murdoch, David R

2008-03-15

The laboratory diagnosis of invasive pneumococcal disease (IPD) continues to rely on culture-based methods that have been used for many decades. The most significant recent developments have occurred with antigen detection assays, whereas the role of nucleic acid amplification tests has yet to be fully clarified. Despite developments in laboratory diagnostics, a microbiological diagnosis is still not made in most cases of IPD, particularly for pneumococcal pneumonia. The limitations of existing diagnostic tests impact the ability to obtain accurate IPD burden data and to assess the effectiveness of control measures, such as vaccination, in addition to the ability to diagnose IPD in individual patients. There is an urgent need for improved diagnostic tests for pneumococcal disease--especially tests that are suitable for use in underresourced countries.

Speeding disease gene discovery by sequence based candidate prioritization

Directory of Open Access Journals (Sweden)

Porteous David J

2005-03-01

Full Text Available Abstract Background Regions of interest identified through genetic linkage studies regularly exceed 30 centimorgans in size and can contain hundreds of genes. Traditionally this number is reduced by matching functional annotation to knowledge of the disease or phenotype in question. However, here we show that disease genes share patterns of sequence-based features that can provide a good basis for automatic prioritization of candidates by machine learning. Results We examined a variety of sequence-based features and found that for many of them there are significant differences between the sets of genes known to be involved in human hereditary disease and those not known to be involved in disease. We have created an automatic classifier called PROSPECTR based on those features using the alternating decision tree algorithm which ranks genes in the order of likelihood of involvement in disease. On average, PROSPECTR enriches lists for disease genes two-fold 77% of the time, five-fold 37% of the time and twenty-fold 11% of the time. Conclusion PROSPECTR is a simple and effective way to identify genes involved in Mendelian and oligogenic disorders. It performs markedly better than the single existing sequence-based classifier on novel data. PROSPECTR could save investigators looking at large regions of interest time and effort by prioritizing positional candidate genes for mutation detection and case-control association studies.

In Vitro and In Vivo SERS Biosensing for Disease Diagnosis

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T. Joshua Moore

2018-05-01

Full Text Available For many disease states, positive outcomes are directly linked to early diagnosis, where therapeutic intervention would be most effective. Recently, trends in disease diagnosis have focused on the development of label-free sensing techniques that are sensitive to low analyte concentrations found in the physiological environment. Surface-enhanced Raman spectroscopy (SERS is a powerful vibrational spectroscopy that allows for label-free, highly sensitive, and selective detection of analytes through the amplification of localized electric fields on the surface of a plasmonic material when excited with monochromatic light. This results in enhancement of the Raman scattering signal, which allows for the detection of low concentration analytes, giving rise to the use of SERS as a diagnostic tool for disease. Here, we present a review of recent developments in the field of in vivo and in vitro SERS biosensing for a range of disease states including neurological disease, diabetes, cardiovascular disease, cancer, and viral disease.

Review of Coconut “Lethal Yellowing” type diseases Diversity, variability and diagnosis

Directory of Open Access Journals (Sweden)

Dollet Michel

2009-03-01

Full Text Available Coconut palms (Cocos nucifera L. can be affected by several types of Lethal Yellowing (LY diseases worldwide. Some of the syndromes are caused by phytoplasmas, small bacteria that are impossible to detect by light microscopy. Amplification of a given gene of the phytoplasmas by polymerase chain reaction (PCR is the most convenient diagnosis method. The problem is that there are at least 28 “groups” of phytoplasmas and only one pair of primers -P1/P7- commonly used for PCR. As these primers belong to a very conserved gene, false positives are frequent. Consequently, alternative primers specific to one “strain” (or subgroup have to be used, such as LY-F/LY-R for the Caribbean LY, Rohde primers for LD Tanzania. Such specific primers are sometimes restrictive. Indeed, there is variability within each strain and the sequence of the primers has to be adapted to that variability. There are at least five LY subgroups. The subgroups can only be identified by restriction fragment length polymorphism or sequencing. In Africa, two subgroups of LY phytoplasmas have been identified so far.

A multi-slice gradient sequence for contrast enhanced MR diagnosis of intracranial tumours

International Nuclear Information System (INIS)

Schoerner, W.; Sander, B.; Kornmesser, W.; Laniado, M.; Nakamura, T.; Felix, R.

1988-01-01

A multi-slice gradient echo sequence (FLASH) was compared with a conventional spin-echo (SE) technique with regard to its value for contrast enhanced MR diagnosis. In 28 patients with cerebral tumours, SE images (SE 400/30; four images/3.4 minutes) and FLASH images (FLASH 315/14; 15 images/1.4 minutes) were obtained before and after gadolinium DTPA. After gadolinium-DTPA results were comparable for both techniques with respect to contrast enhancement, tumor contrast and delineation. Because of the higher efficiency of the FLASH 315/14 technique, this sequence is the method of choice for contrast enhanced cerebral MR imaging. (orig.) [de

International Cooperation to Enable the Diagnosis of All Rare Genetic Diseases.

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Boycott, Kym M; Rath, Ana; Chong, Jessica X; Hartley, Taila; Alkuraya, Fowzan S; Baynam, Gareth; Brookes, Anthony J; Brudno, Michael; Carracedo, Angel; den Dunnen, Johan T; Dyke, Stephanie O M; Estivill, Xavier; Goldblatt, Jack; Gonthier, Catherine; Groft, Stephen C; Gut, Ivo; Hamosh, Ada; Hieter, Philip; Höhn, Sophie; Hurles, Matthew E; Kaufmann, Petra; Knoppers, Bartha M; Krischer, Jeffrey P; Macek, Milan; Matthijs, Gert; Olry, Annie; Parker, Samantha; Paschall, Justin; Philippakis, Anthony A; Rehm, Heidi L; Robinson, Peter N; Sham, Pak-Chung; Stefanov, Rumen; Taruscio, Domenica; Unni, Divya; Vanstone, Megan R; Zhang, Feng; Brunner, Han; Bamshad, Michael J; Lochmüller, Hanns

2017-05-04

Provision of a molecularly confirmed diagnosis in a timely manner for children and adults with rare genetic diseases shortens their "diagnostic odyssey," improves disease management, and fosters genetic counseling with respect to recurrence risks while assuring reproductive choices. In a general clinical genetics setting, the current diagnostic rate is approximately 50%, but for those who do not receive a molecular diagnosis after the initial genetics evaluation, that rate is much lower. Diagnostic success for these more challenging affected individuals depends to a large extent on progress in the discovery of genes associated with, and mechanisms underlying, rare diseases. Thus, continued research is required for moving toward a more complete catalog of disease-related genes and variants. The International Rare Diseases Research Consortium (IRDiRC) was established in 2011 to bring together researchers and organizations invested in rare disease research to develop a means of achieving molecular diagnosis for all rare diseases. Here, we review the current and future bottlenecks to gene discovery and suggest strategies for enabling progress in this regard. Each successful discovery will define potential diagnostic, preventive, and therapeutic opportunities for the corresponding rare disease, enabling precision medicine for this patient population. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Modeling the Process of Event Sequence Data Generated for Working Condition Diagnosis

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Jianwei Ding

2015-01-01

Full Text Available Condition monitoring systems are widely used to monitor the working condition of equipment, generating a vast amount and variety of telemetry data in the process. The main task of surveillance focuses on analyzing these routinely collected telemetry data to help analyze the working condition in the equipment. However, with the rapid increase in the volume of telemetry data, it is a nontrivial task to analyze all the telemetry data to understand the working condition of the equipment without any a priori knowledge. In this paper, we proposed a probabilistic generative model called working condition model (WCM, which is capable of simulating the process of event sequence data generated and depicting the working condition of equipment at runtime. With the help of WCM, we are able to analyze how the event sequence data behave in different working modes and meanwhile to detect the working mode of an event sequence (working condition diagnosis. Furthermore, we have applied WCM to illustrative applications like automated detection of an anomalous event sequence for the runtime of equipment. Our experimental results on the real data sets demonstrate the effectiveness of the model.

Attitudes in Patients with Autosomal Dominant Polycystic Kidney Disease Toward Prenatal Diagnosis and Preimplantation Genetic Diagnosis.

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Swift, Oscar; Vilar, Enric; Rahman, Belinda; Side, Lucy; Gale, Daniel P

2016-12-01

No recommendations currently exist regarding implementation of both prenatal diagnosis and preimplantation genetic diagnosis (PGD) for autosomal dominant polycystic kidney disease (ADPKD). This study evaluated attitudes in ADPKD patients with either chronic kidney disease (CKD) stages I-IV or end-stage renal failure (ESRF) toward prenatal diagnosis and PGD. Ninety-six ADPKD patients were recruited from an outpatient clinic, wards, and dialysis units. Thirty-eight patients had ESRF and 58 had CKD stages I-IV. Participants were given an information sheet on prenatal diagnosis and PGD and subsequently completed a questionnaire. The median age of participants was 51.5 years. Seventeen percent of ADPKD patients with CKD and 18% of ADPKD patients with ESRF would consider prenatal diagnosis and termination of pregnancy for ADPKD. Fifty percent with CKD would have opted for PGD (or might consider it in the future) were it available and funded by the UK National Health Service, compared to 63% in the ESRF group (p = 0.33). Sixty-nine percent in the CKD group and 68% in the ESRF group believed that PGD should be offered to other patients. There was a spectrum of attitudes among this cohort. A proportion of patients believe that PGD should be made available to prospective parents with this disease. The discrepancy between the low proportion (17% CKD, 18% ESRF) who would consider prenatal diagnosis and termination of pregnancy and the higher number who hypothetically express an intention or wish to access PGD (50% CKD and 63% ESRF) indicates far greater acceptability for diagnostic methods that occur before embryo implantation. It is not known how the development of methods to identify patients whose renal function is likely to decline rapidly and treatments altering the natural history of ADPKD will affect these attitudes.

Pelvic inflammatory disease: diagnosis and treatment in the emergency department [digest].

Science.gov (United States)

Bugg, Charles Walter; Taira, Taku; Zaurova, Milana

2016-12-22

Pelvic inflammatory disease is a common disease that is associated with significant complications including infertility, chronic pelvic pain, ruptured tubo-ovarian abscess, and ectopic pregnancy. The diagnosis may be delayed when the presentation has nonspecific signs and symptoms. Even when it is properly identified, pelvic inflammatory disease is often treated suboptimally. This review provides evidence-based recommendations for the diagnosis, treatment, disposition, and follow-up of patients with pelvic inflammatory disease. Arranging follow-up of patients within 48 to 72 hours and providing clear patient education are fundamental to ensuring good patient outcomes. Emerging issues, including new pathogens and evolving resistance patterns among pelvic inflammatory disease pathogens are reviewed. [Points & Pearls is a digest of Emergency Medicine Practice].

Chlorophyll as a biomarker for early disease diagnosis

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Manzoor Atta, Babar; Saleem, M.; Ali, Hina; Arshad, Hafiz Muhammad Imran; Ahmed, M.

2018-06-01

The current study was designed to identify the stage for the diagnosis of disease before visible symptoms appeared. Fluorescence spectroscopy has been employed to identify disease signatures for its early diagnosis in rice plant leaves. Bacterial leaf blight (BLB) diseased and healthy leaf samples were collected from the rice fields in September, 2017 which were then used to record spectra using an excitation wavelength at 410 nm. The spectral range of emission was set from 420 to 800 nm which covers the blue–green and the chlorophyll bands. It was found that diseased leaves have a narrower ‘chlorophyll a’ band than healthy ones, and furthermore, that the emission band at 730 nm was either declined or depleted in the sample with high infection symptoms. In contrast, the blue–green region was observed to increase due to the emergence of disease. As the band intensity of chlorophyll decreases during infection, this decrease in chlorophyll content and increase in the blue–green spectral region could provide a new approach for predicting BLB at an early stage. The important finding was that the chlorophyll degradation and rise in the blue–green region take place in leaves with BLB or during BLB infection. Principal component analysis has been applied to spectral data which successfully separated diseased samples from healthy ones even with very small spectral variations.

Molecular Findings Among Patients Referred for Clinical Whole-Exome Sequencing

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Yang, Yaping; Muzny, Donna M.; Xia, Fan; Niu, Zhiyv; Person, Richard; Ding, Yan; Ward, Patricia; Braxton, Alicia; Wang, Min; Buhay, Christian; Veeraraghavan, Narayanan; Hawes, Alicia; Chiang, Theodore; Leduc, Magalie; Beuten, Joke; Zhang, Jing; He, Weimin; Scull, Jennifer; Willis, Alecia; Landsverk, Megan; Craigen, William J.; Bekheirnia, Mir Reza; Stray-Pedersen, Asbjorg; Liu, Pengfei; Wen, Shu; Alcaraz, Wendy; Cui, Hong; Walkiewicz, Magdalena; Reid, Jeffrey; Bainbridge, Matthew; Patel, Ankita; Boerwinkle, Eric; Beaudet, Arthur L.; Lupski, James R.; Plon, Sharon E.; Gibbs, Richard A.; Eng, Christine M.

2015-01-01

IMPORTANCE Clinical whole-exome sequencing is increasingly used for diagnostic evaluation of patients with suspected genetic disorders. OBJECTIVE To perform clinical whole-exome sequencing and report (1) the rate of molecular diagnosis among phenotypic groups, (2) the spectrum of genetic alterations contributing to disease, and (3) the prevalence of medically actionable incidental findings such as FBN1 mutations causing Marfan syndrome. DESIGN, SETTING, AND PATIENTS Observational study of 2000 consecutive patients with clinical whole-exome sequencing analyzed between June 2012 and August 2014. Whole-exome sequencing tests were performed at a clinical genetics laboratory in the United States. Results were reported by clinical molecular geneticists certified by the American Board of Medical Genetics and Genomics. Tests were ordered by the patient’s physician. The patients were primarily pediatric (1756 [88%]; mean age, 6 years; 888 females [44%], 1101 males [55%], and 11 fetuses [1% gender unknown]), demonstrating diverse clinical manifestations most often including nervous system dysfunction such as developmental delay. MAIN OUTCOMES AND MEASURES Whole-exome sequencing diagnosis rate overall and by phenotypic category, mode of inheritance, spectrum of genetic events, and reporting of incidental findings. RESULTS A molecular diagnosis was reported for 504 patients (25.2%) with 58% of the diagnostic mutations not previously reported. Molecular diagnosis rates for each phenotypic category were 143/526 (27.2%; 95% CI, 23.5%–31.2%) for the neurological group, 282/1147 (24.6%; 95% CI, 22.1%–27.2%) for the neurological plus other organ systems group, 30/83 (36.1%; 95% CI, 26.1%–47.5%) for the specific neurological group, and 49/244 (20.1%; 95% CI, 15.6%–25.8%) for the nonneurological group. The Mendelian disease patterns of the 527 molecular diagnoses included 280 (53.1%) autosomal dominant, 181 (34.3%) autosomal recessive (including 5 with uniparental disomy

Diagnosis and management of refractory celiac disease: a systematic review.

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Labidi, Asma; Serghini, Meriem; Karoui, Sami; Boubaker, Jalel; Filali, Azza

2013-01-01

Refractory celiac disease is defined by persisting malabsorptive symptoms in spite of a strict gluten free diet for at least 6 to 12 months. Alternatives to gluten free diet seem to be still controversial. To describe the clinical and epidemiologic aspects of refractory celiac disease, and to identify therapeutic options in this condition. Systematic review and critical analysis of observational studies, clinical trials and case reports that focused on diagnosis and management of refractory celiac disease. Refractory celiac disease can be classified as type 1 or type 2 according to the phenotype of intraepithelial lymphocytes. Great complications such as enteropathy-associated T-cell lymphoma may occur in a subgroup of these patients mainly in refractory celiac disease type 2. Curative therapies are still lacking. Refractory celiac disease remains a diagnosis of exclusion. Its prognosis remains still dismal by the absence yet of curative therapies. However, some new treatments seem to hold promise during few cohort-studies.

Diagnosis and classification of Goodpasture's disease (anti-GBM).

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Hellmark, Thomas; Segelmark, Mårten

2014-01-01

Goodpasture's disease or anti-glomerular basement membrane disease (anti-GBM-disease) is included among immune complex small vessel vasculitides. The definition of anti-GBM disease is a vasculitis affecting glomerular capillaries, pulmonary capillaries, or both, with GBM deposition of anti-GBM autoantibodies. The disease is a prototype of autoimmune disease, where the patients develop autoantibodies that bind to the basement membranes and activate the classical pathway of the complement system, which start a neutrophil dependent inflammation. The diagnosis of anti-GBM disease relies on the detection of anti-GBM antibodies in conjunction with glomerulonephritis and/or alveolitis. Overt clinical symptoms are most prominent in the glomeruli where the inflammation usually results in a severe rapidly progressive glomerulonephritis. Despite modern treatment less than one third of the patients survive with a preserved kidney function after 6 months follow-up. Frequencies vary from 0.5 to 1 cases per million inhabitants per year and there is a strong genetic linkage to HLA-DRB1(∗)1501 and DRB1(∗)1502. Essentially, anti-GBM disease is now a preferred term for what was earlier called Goodpasture's syndrome or Goodpasture's disease; anti-GBM disease is now classified as small vessel vasculitis caused by in situ immune complex formation; the diagnosis relies on the detection of anti-GBM in tissues or circulation in conjunction with alveolar or glomerular disease; therapy is effective only when detected at an early stage, making a high degree of awareness necessary to find these rare cases; 20-35% have anti-GBM and MPO-ANCA simultaneously, which necessitates testing for anti-GBM whenever acute test for ANCA is ordered in patients with renal disease. Copyright © 2014 Elsevier Ltd. All rights reserved.

Diagnosis of suspected venous thromboembolic disease in pregnancy

International Nuclear Information System (INIS)

Scarsbrook, A.F.; Evans, A.L.; Owen, A.R.; Gleeson, F.V.

2006-01-01

Venous thromboembolic disease is a leading cause of maternal mortality during pregnancy. Early and accurate radiological diagnosis is essential as anticoagulation is not without risk and clinical diagnosis is unreliable. Although the disorder is potentially treatable, unnecessary treatment should be avoided. Most of the diagnostic imaging techniques involve ionizing radiation which exposes both the mother and fetus to finite radiation risks. There is a relative lack of evidence in the literature to guide clinicians and radiologists on the most appropriate method of assessing this group of patients. This article will review the role of imaging of suspected venous thromboembolic disease in pregnant patients, highlight contentious issues such as radiation risk, intravenous contrast use in pregnancy and discuss the published guidelines, as well as suggesting an appropriate imaging algorithm based on the available evidence

The potential use of Raman spectroscopy for the diagnosis of Alzheimer's disease

Science.gov (United States)

Sudworth, Caroline D.; Archer, John K. J.; Mann, David

2005-09-01

Alzheimer's disease currently affects over 800,000 people in the UK, and this figure is set to exceed 1.5 million by 2050. The disease causes a severe breakdown of the brain, resulting in the progressive decline in the mental health of the patient. It also remains without a long-term cure. A definitive diagnosis of the disease can only be gained at post-mortem, whilst other technologies are limited to monitoring the physical breakdown of the brain. The early identification of the chemicals responsible for the disease, and their structure, is therefore essential for improved diagnosis, treatment and care. This research demonstrates the use of Raman spectroscopy, and principle components analysis, as a method for the diagnosis, and examination of, the specific proteins responsible for Alzheimer's disease. Analyses of ethically approved ex vivo brain tissues from normal elderly (n=3), Alzheimer's disease (n=12) and Huntingdon's disease (n=3) brain sections (from the frontal and occipital lobes) are presented. Subsequently, a further 12 blinded individual samples were examined and the preliminary results are presented. Spectra originating from these tissues are highly reproducible, and results indicate a vital difference in protein content and protein conformation, relating to the abnormally high levels of aggregated proteins in the diseased tissues. Principle components analysis has been shown to differentiate normal elderly tissues from diseased tissues. These results show great promise for the early identification of Alzheimer's disease, and secondary information regarding other brain diseases and dementias. These results demonstrate the potential use of Raman spectroscopy as a possible non-invasive, non-destructive tool for the early diagnosis of Alzheimer's disease.

[Advance in the methods of preimplantation genetic diagnosis for single gene diseases].

Science.gov (United States)

Ren, Yixin; Qiao, Jie; Yan, Liying

2017-06-10

More than 7000 single gene diseases have been identified and most of them lack effective treatment. As an early form of prenatal diagnosis, preimplantation genetic diagnosis (PGD) is a combination of in vitro fertilization and genetic diagnosis. PGD has been applied in clinics for more than 20 years to avoid the transmission of genetic defects through analysis of embryos at early stages of development. In this paper, a review for the recent advances in PGD for single gene diseases is provided.

Bronchoscopic cryobiopsy for the diagnosis of diffuse parenchymal lung disease.

Directory of Open Access Journals (Sweden)

Jonathan A Kropski

Full Text Available Although in some cases clinical and radiographic features may be sufficient to establish a diagnosis of diffuse parenchymal lung disease (DPLD, surgical lung biopsy is frequently required. Recently a new technique for bronchoscopic lung biopsy has been developed using flexible cryo-probes. In this study we describe our clinical experience using bronchoscopic cryobiopsy for diagnosis of diffuse lung disease.A retrospective study of subjects who had undergone bronchoscopic cryobiopsy for evaluation of DPLD at an academic tertiary care center from January 1, 2012 through January 15, 2013 was performed. The procedure was performed using a flexible bronchoscope to acquire biopsies of lung parenchyma. H&E stained biopsies were reviewed by an expert lung pathologist.Twenty-five eligible subjects were identified. With a mean area of 64.2 mm(2, cryobiopsies were larger than that typically encountered with traditional transbronchial forceps biopsy. In 19 of the 25 subjects, a specific diagnosis was obtained. In one additional subject, biopsies demonstrating normal parenchyma were felt sufficient to exclude diffuse lung disease as a cause of dyspnea. The overall diagnostic yield of bronchoscopic cryobiopsy was 80% (20/25. The most frequent diagnosis was usual interstitial pneumonia (UIP (n = 7. Three of the 25 subjects ultimately required surgical lung biopsy. There were no significant complications.In patients with suspected diffuse parenchymal lung disease, bronchoscopic cryobiopsy is a promising and minimally invasive approach to obtain lung tissue with high diagnostic yield.

Biomarkers in rheumatic diseases: how can they facilitate diagnosis and assessment of disease activity?

Science.gov (United States)

Mohan, Chandra; Assassi, Shervin

2015-11-26

Serological and proteomic biomarkers can help clinicians diagnose rheumatic diseases earlier and assess disease activity more accurately. These markers have been incorporated into the recently revised classification criteria of several diseases to enable early diagnosis and timely initiation of treatment. Furthermore, they also facilitate more accurate subclassification and more focused monitoring for the detection of certain disease manifestations, such as lung and renal involvement. These biomarkers can also make the assessment of disease activity and treatment response more reliable. Simultaneously, several new serological and proteomic biomarkers have become available in the routine clinical setting--for example, a protein biomarker panel for rheumatoid arthritis and a myositis antibody panel for dermatomyositis and polymyositis. This review will focus on commercially available antibody and proteomic biomarkers in rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis (scleroderma), dermatomyositis and polymyositis, and axial spondyloarthritis (including ankylosing spondylitis). It will discuss how these markers can facilitate early diagnosis as well as more accurate subclassification and assessment of disease activity in the clinical setting. The ultimate goal of current and future biomarkers in rheumatic diseases is to enable early detection of these diseases and their clinical manifestations, and to provide effective monitoring and treatment regimens that are tailored to each patient's needs and prognosis. © BMJ Publishing Group Ltd 2015.

MR imaging at 0.5 Tesla with FLAIR sequence in the diagnosis of acute subarachnoid hemorrhage

International Nuclear Information System (INIS)

Kopsa, W.; Leitner, H.; Tscholakoff, D.; Perneczky, G.

1998-01-01

Purpose: Evaluation of MR imaging in patients with acute subarachnoid hemorrhage (SAH) at 0.5 Tesla using the FLAIR (Fluid Attenuated Inversion Recovery) sequenze. Additionally, the value of MR angiographie (MRA) in the diagnosis of intracranial aneurysms was assessed. Materials and Methods: 19 patients with suspected acute SAH were included in this study. MR imaging was performed using an axial FLAIR sequence and axial T 1 , T 2 and PD weighted sequences. In 16 patients an additional MRA (3D-TOF) was performed. 10 patients without SAH were examined as a control group. At the end of the study the 29 MR examinations were randomised and the images were read by two experienced radiologists; subsequently a consensus interpretation was made. Results: In 16 patients an acute SAH was verified with the FLAIR sequence, in 13 cases the origin of hemorrhage was found during surgery. In the consensus interpretation of the MR images all cases were diagnosed properly. 12 of the 16 MRA studies were of diagnostic quality, but only 6 cases were interpreted correctly. Conclusion: The FLAIR sequence at 0.5 Tesla proved effective in the diagnosis of acute SAH. MRA at 0.5 Tesla failed in the detection of intracranial aneurysms. (orig.) [de

Difficulties in diagnosis and treatment of Paget’s disease

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Aleksandra Kawalec

2016-12-01

Full Text Available Paget’s disease is a rare finding in Poland. It is a disorder of the osteoarticular system, which, in adults, mostly affects people over 55 years of age. The clinical picture varies, depending on the location of the lesions, making the diagnosis difficult, sometimes taking many years for a correct diagnosis to be made. In etiopathogenesis, genetic predispositions as well as viral infections play an important role. From the genetic point of view, Paget’s disease is heterogeneous, as numerous mutations are known, and the genotype to phenotype relationship is unclear. The first phase of the disease is characterized by an increased osteocytes activity, due to morphologically changed and RANKL overstimulated osteocytes. This leads to an intensification of ossification processes that occur in a chaotic manner. Therefore, the resulting bone is weak, extensively vascularized and there is an increased risk of fracture or deformity. Clinical manifestations of Paget’s disease might include pain, excessive warmth, bone deformations, degenerative lesions in the adjacent joints, compression of the neural structures, hearing loss, and dilated cardiomiopathy. Other possible complications include the development of benign and malignant bone tumors and hypercalcaemia in the case of immobilization. An elevated level of serum alkaline phosphatase, bone x-ray and bone scintigraphy are crucial in making the diagnosis. The disease should be distinguished from osteomalacia, osteoporosis, hyperparathyroidism and multiple myeloma. Bisphosphonates at doses higher than those applied for osteoporosis are an effective treatment. The occurrence of orthopedic, neurological and laryngological complications is often a reason for surgical intervention.

Crohn Disease: Epidemiology, Diagnosis, and Management.

Science.gov (United States)

Feuerstein, Joseph D; Cheifetz, Adam S

2017-07-01

Crohn disease is a chronic idiopathic inflammatory bowel disease condition characterized by skip lesions and transmural inflammation that can affect the entire gastrointestinal tract from the mouth to the anus. For this review article, we performed a review of articles in PubMed through February 1, 2017, by using the following Medical Subject Heading terms: crohns disease, crohn's disease, crohn disease, inflammatory bowel disease, and inflammatory bowel diseases. Presenting symptoms are often variable and may include diarrhea, abdominal pain, weight loss, nausea, vomiting, and in certain cases fevers or chills. There are 3 main disease phenotypes: inflammatory, structuring, and penetrating. In addition to the underlying disease phenotype, up to a third of patients will develop perianal involvement of their disease. In addition, in some cases, extraintestinal manifestations may develop. The diagnosis is typically made with endoscopic and/or radiologic findings. Disease management is usually with pharmacologic therapy, which is determined on the basis of disease severity and underlying disease phenotype. Although the goal of management is to control the inflammation and induce a clinical remission with pharmacologic therapy, most patients will eventually require surgery for their disease. Unfortunately, surgery is not curative and patients still require ongoing therapy even after surgery for disease recurrence. Importantly, given the risks of complications from both Crohn disease and the medications used to treat the disease process, primary care physicians play an important role in optimizing the preventative care management to reduce the risk of complications. Copyright © 2017 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

Radiological diagnosis of skeletal metastases

International Nuclear Information System (INIS)

Soederlund, V.

1996-01-01

The clinical management of patients with skeletal metastases puts new demands on imaging. The radiological imaging in screening for skeletal metastases entails detection, metastatic site description and radiologically guided biopsy for morphological typing and diagnosis. Regarding sensitivity and the ease in performing surveys of the whole skeleton, radionuclide bone scintigraphy still is the first choice in routine follow-up of asymptomatic patients with metastatic disease of the skeleton. A negative scan has to be re-evaluated with other findings, with emphasis on the possibility of a false-negative result. Screening for metastases in patients with local symptoms or pain is best accomplished by a combination of radiography and MRI. Water-weighted sequences are superior in sensitivity and in detection of metastases. Standard spin-echo sequences on the other hand are superior in metastatic site description and in detection of intraspinal metastases. MRI is helpful in differentiating between malignant disease, infection, benign vertebral collapse, insufficiency fracture after radiation therapy, degenerative vertebral disease and benign skeletal lesions. About 30% of patients with known cancer have benign causes of radiographic abnormalities. Most of these are related to degenerative diseases and are often easily diagnosed. However, due to overlap in MRI characteristics, bone biopsy sometimes is essential for differentiating between malignant and nonmalignant lesions. Performing bone biopsy and aspiration cytology by radiologist and cytologist in co-operation has proven highly accurate in diagnosing bone lesions. The procedure involves low risk to the patient and provides a morphological diagnosis. Once a suspected metastatic lesion is detected, irrespective of modality, the morphological diagnosis determines the appropriate work-up imaging with respect to the therapy alternatives. (orig./VHE)

The capabilities of computed tomography in diagnosis of purulent destructive lung diseases

International Nuclear Information System (INIS)

Churilyin, R.Yu.

2012-01-01

Simultaneous use of traditional tomography and CT increased the efficacy of the diagnosis and allowed to limit the use of invasive methods of investigations. Computed tomography of purulent destructive lung diseases allows timely diagnosis and differential diagnosis using characteristic signs in some case

The diagnosis of gastroesophageal reflux disease in children

International Nuclear Information System (INIS)

El-Mouzan, Mohammad I.; Abdullah, Asaad M.

2002-01-01

Gastroesophageal reflux disease is a common disorder affecting children worldwide. The objective of this study is to report our experience on the accuracy of tests used for the diagnosis ofgastroesophageal reflux disease with emphasis on the advantages and disadvantages of each of them. This study took place in the Pediatric Gastroenterology Division, Department of Pediatrics, College of Medicine and King Khalid University Hospital, Riyadh, Kingdom of Saudi Arabia, during the period of 1994 through to 1999. Results of barium meal, 24-hour esophageal pH monitoring, endoscopy, and gastrointestinal scintigraphy are analyzed and compared in children with and without gastroesophageal reflux disease. One hundred and forty-four children were investigated. The diagnosis was confirmed in 85 and excluded in 59 children, who will be considered as patients without gastroesophageal reflux disease. The results of barium meal, 24 hour pH monitoring, endoscopy, and gastrointestinal scintigraphy were positive in 80%, 78%, 92%, and 70% of the patients with gastroesophageal disease. The same studies were falsely positive in 29%, 9%, 19%, and 0% of those without gastroesophageal reflux disease. Esophageal pH was the most specific diagnostic study (91%), whereas endoscopy was the most sensitive (92%) and had the best positive predictive value (95%). The results of this study are similar to reports from other parts of the world. It is stressed that all procedures have important advantages and disadvantages indicating that the selection of procedures should be individualized and based on the clinical situation. (author)

Pentraxins as Key Disease Markers for Periodontal Diagnosis

Directory of Open Access Journals (Sweden)

Rahul Kathariya

2013-01-01

Full Text Available Periodontal diseases are characterized by a complex set of biologic interactions between a diverse and dynamic microbial ecosystem and the host’s multifaceted and responsive immune and inflammatory machinery. Such interactions between microbial pathogens and various host response systems play a critical role in the development and progression of periodontal disease via the release of inflammatory and immune mediators. Advances in periodontal disease diagnostic are moving toward methods whereby periodontal risk can be identified and quantified by detecting such inflammatory mediators in its sequential pathophysiology. Pentraxins (PTXs are classical mediators of inflammation and markers of acute-phase reaction. They are a super family of multifunctional molecules characterized by multimeric structure, divided into “short” PTXs and “long” PTXs. C-reactive protein (CRP and pentraxin-3 (PTX3 are prototypic molecules of the short and long PTX family, respectively. Evidence suggests that PTXs acts as a non-redundant component of the humoral arm of innate immunity, downstream of, and complementary to, cellular recognition, as well as a tuner of inflammation. CRP is a cheaper biomarker and more readily available in everyday clinical practice compared with other inflammatory markers, on the other hand, PTX3 is believed to be the true independent indicator of disease activity and could have clinical implication in diagnosing the “at site” inflammatory status of the periodontal disease. These pentraxins are sensitive and specific in the diagnosis and prognosis of chronic diseases. Thus the pentraxins could be used as preferred biomarkers in periodontal disease diagnosis.

Magnetic resonance (MR) in the diagnosis of pancreatic disease

International Nuclear Information System (INIS)

Anacker, H.; Rupp, N.; Reiser, M.; Technische Univ. Muenchen

1984-01-01

New methods of examination are measured in terms of the efficiency of their predecessors. The introduction of endoscopic retrograde cholangiopancreatography (ERCP) and computerised tomography (CT) constituted a turning point in the diagnosis of pancreatic disease. In this incipient stages as a clinical diagnostic method, the question is raised whether or not there is evidence that magnetic resonance (MR) can supplement, improve upon or replace the customary methods. It must, however, be taken into account that the technical development of MR is still in progress and that clinical experience with MR in the diagnosis of pancreatic disease, as in other areas, is still insufficient. At this point it is only possible to survey the trends. (orig.)

Applying Next Generation Sequencing to Skeletal Development and Disease

OpenAIRE

Bowen, Margot Elizabeth

2013-01-01

Next Generation Sequencing (NGS) technologies have dramatically increased the throughput and lowered the cost of DNA sequencing. In this thesis, I apply these technologies to unresolved questions in skeletal development and disease. Firstly, I use targeted re-sequencing of genomic DNA to identify the genetic cause of the cartilage tumor syndrome, metachondromatosis (MC). I show that the majority of MC patients carry heterozygous loss-of-function mutations in the PTPN11 gene, which encodes a p...

Rapid prenatal diagnosis using targeted exome sequencing: a cohort study to assess feasibility and potential impact on prenatal counseling and pregnancy management.

Science.gov (United States)

Chandler, Natalie; Best, Sunayna; Hayward, Jane; Faravelli, Francesca; Mansour, Sahar; Kivuva, Emma; Tapon, Dagmar; Male, Alison; DeVile, Catherine; Chitty, Lyn S

2018-03-29

PurposeUnexpected fetal abnormalities occur in 2-5% of pregnancies. While traditional cytogenetic and microarray approaches achieve diagnosis in around 40% of cases, lack of diagnosis in others impedes parental counseling, informed decision making, and pregnancy management. Postnatally exome sequencing yields high diagnostic rates, but relies on careful phenotyping to interpret genotype results. Here we used a multidisciplinary approach to explore the utility of rapid fetal exome sequencing for prenatal diagnosis using skeletal dysplasias as an exemplar.MethodsParents in pregnancies undergoing invasive testing because of sonographic fetal abnormalities, where multidisciplinary review considered skeletal dysplasia a likely etiology, were consented for exome trio sequencing (both parents and fetus). Variant interpretation focused on a virtual panel of 240 genes known to cause skeletal dysplasias.ResultsDefinitive molecular diagnosis was made in 13/16 (81%) cases. In some cases, fetal ultrasound findings alone were of sufficient severity for parents to opt for termination. In others, molecular diagnosis informed accurate prediction of outcome, improved parental counseling, and enabled parents to terminate or continue the pregnancy with certainty.ConclusionTrio sequencing with expert multidisciplinary review for case selection and data interpretation yields timely, high diagnostic rates in fetuses presenting with unexpected skeletal abnormalities. This improves parental counseling and pregnancy management.Genetics in Medicine advance online publication, 29 March 2018; doi:10.1038/gim.2018.30.

Five-year risk of HIV diagnosis subsequent to 147 hospital-based indicator diseases

DEFF Research Database (Denmark)

Omland, Lars Haukali; Legarth, Rebecca; Ahlström, Magnus Glindvad

2016-01-01

. To estimate the risk of HIV diagnosis in the general population without any indicator diseases, we calculated the FYRHD starting at age 25, 35, 45, and 55 years. RESULTS: The risk in the male general population was substantially higher than the female general population, and the risk was lower in the older...... with relevant indicator diseases are nonexistent. METHODS: In a nationwide population-based cohort study encompassing all Danish residents aged 20-60 years during 1994-2013, we estimated the 5-year risk of an HIV diagnosis (FYRHD) after a first-time diagnosis of 147 prespecified potential indicator diseases...

Current status of gastroesophageal reflux disease : diagnosis and treatment.

Science.gov (United States)

Chuang, Tang-Wei; Chen, Shou-Chien; Chen, Kow-Tong

2017-01-01

The aim of this study was to explore the recent advances in diagnosis and treatment of gastroesophageal reflux disease (GERD). Previous studies were searched using the terms "gastroesophageal reflux disease" and "diagnosis" or "treatment" in Medline and Pubmed. Articles that were not published in the English language, manuscripts without an abstract, reviews, meta-analysis, and opinion articles were excluded from the review. After a preliminary screening, all of the articles were reviewed and synthesized to provide an overview of the contemporary approaches to GERD. GERD has a variety of symptomatic manifestations, which can be grouped into typical, atypical and extra-esophageal symptoms. Those with the highest specificity for GERD are acid regurgitation and heartburn. In the absence of other alarming symptoms, these symptoms allow one to make a presumptive diagnosis of GERD and initiate empiric therapy. GERD-associated complications include erosive esophagitis, peptic stricture, Barrett's esophagus, esophageal adenocarcinoma and pulmonary disease. Management of GERD may involve lifestyle modifications, medical and surgical therapy. Medical therapy involves acid suppression, which can be achieved with antacids, histamine-receptor antagonists or proton-pump inhibitors. Whereas most patients can be effectively managed with medical therapy, others may go on to require anti-reflux surgery after undergoing a proper pre-operative evaluation. The management of this disease requires a complex approach. Maintenance therapy of GERD after using anti-secretory drugs should be continuously monitored. © Acta Gastro-Enterologica Belgica.

Hypotonic duodenography and endoscopic retrograde pancreatography in the diagnosis of pancreatic disease

International Nuclear Information System (INIS)

Lukes, P.J.; Rolny, P.; Nilson, A.E.; Gamklou, R.

1981-01-01

Hypotonic duodenography and endoscopic retrograde pancreatography were performed in 45 non-icteric patients with suggested pancreatic disease or long-standing upper gastrointestinal symptoms. The accuracy of each method in the diagnosis of pancreatic disease was compared. Hypotonic duodenography revealed pancreatitis in 48 per cent and ERP in 83 per cent of the cases. All 6 pancreatic tumours were detected at ERP and 3 at duodenography. The role of hypotonic duodenography and endoscopic retrograde pancreatography in the diagnosis of pancreatic disease is discussed. (Auth.)

Hybrid Disease Diagnosis Using Multiobjective Optimization with Evolutionary Parameter Optimization

Directory of Open Access Journals (Sweden)

MadhuSudana Rao Nalluri

2017-01-01

Full Text Available With the widespread adoption of e-Healthcare and telemedicine applications, accurate, intelligent disease diagnosis systems have been profoundly coveted. In recent years, numerous individual machine learning-based classifiers have been proposed and tested, and the fact that a single classifier cannot effectively classify and diagnose all diseases has been almost accorded with. This has seen a number of recent research attempts to arrive at a consensus using ensemble classification techniques. In this paper, a hybrid system is proposed to diagnose ailments using optimizing individual classifier parameters for two classifier techniques, namely, support vector machine (SVM and multilayer perceptron (MLP technique. We employ three recent evolutionary algorithms to optimize the parameters of the classifiers above, leading to six alternative hybrid disease diagnosis systems, also referred to as hybrid intelligent systems (HISs. Multiple objectives, namely, prediction accuracy, sensitivity, and specificity, have been considered to assess the efficacy of the proposed hybrid systems with existing ones. The proposed model is evaluated on 11 benchmark datasets, and the obtained results demonstrate that our proposed hybrid diagnosis systems perform better in terms of disease prediction accuracy, sensitivity, and specificity. Pertinent statistical tests were carried out to substantiate the efficacy of the obtained results.

Magnetic Resonance Techniques Applied to the Diagnosis and Treatment of Parkinson’s Disease

Science.gov (United States)

de Celis Alonso, Benito; Hidalgo-Tobón, Silvia S.; Menéndez-González, Manuel; Salas-Pacheco, José; Arias-Carrión, Oscar

2015-01-01

Parkinson’s disease (PD) affects at least 10 million people worldwide. It is a neurodegenerative disease, which is currently diagnosed by neurological examination. No neuroimaging investigation or blood biomarker is available to aid diagnosis and prognosis. Most effort toward diagnosis using magnetic resonance (MR) has been focused on the use of structural/anatomical neuroimaging and diffusion tensor imaging (DTI). However, deep brain stimulation, a current strategy for treating PD, is guided by MR imaging (MRI). For clinical prognosis, diagnosis, and follow-up investigations, blood oxygen level-dependent MRI, DTI, spectroscopy, and transcranial magnetic stimulation have been used. These techniques represent the state of the art in the last 5 years. Here, we focus on MR techniques for the diagnosis and treatment of Parkinson’s disease. PMID:26191037

Evaluating next-generation sequencing for direct clinical diagnostics in diarrhoeal disease

DEFF Research Database (Denmark)

Joensen, Katrine Grimstrup; Engsbro, A L Ø; Lukjancenko, Oksana

2017-01-01

The accurate microbiological diagnosis of diarrhoea involves numerous laboratory tests and, often, the pathogen is not identified in time to guide clinical management. With next-generation sequencing (NGS) becoming cheaper, it has huge potential in routine diagnostics. The aim of this study...... was to evaluate the potential of NGS-based diagnostics through direct sequencing of faecal samples. Fifty-eight clinical faecal samples were obtained from patients with diarrhoea as part of the routine diagnostics at Hvidovre University Hospital, Denmark. Ten samples from healthy individuals were also included...

Pediatric gastroesophageal reflux disease: Current diagnosis and management

NARCIS (Netherlands)

van der Pol, R.J.

2014-01-01

Pediatric gastroesophageal reflux disease (GERD) is a disorder difficult to diagnose and to treat. Due to the current definition of GERD, i.e. gastroesophageal reflux (GER) causing bothersome symptoms and/or complications, diagnosis is subject to broad interpretation. This thesis consists of studies

Radiological diagnosis of lung diseases

International Nuclear Information System (INIS)

Kauczor, H.U.; Heussel, C.P.; Thelen, M.

2000-01-01

Radiological cross-sectional imaging modalities, particularly computed tomography (CT) have become the mainstays for diagnosing lung disease in recent years. These enable morphological visualization of pathological processes with the greatest possible spatial resolution. Modern technical developments and complementary strategies have led to new applications and new functional assessments which need to be reviewed together with state-of-the-art techniques in nuclear imaging. The diagnosis of pulmonary embolism using spiral CT angiography and magnetic resonance (MR) angiography certainly belongs in this category. CT has become the an alternative modality of first choice, and it is also challenging pulmonary angiography as the gold standard. Direct visualization of patent pulmonary arteries and thromboembolic material is complemented by that of effects on the pulmonary parenchyma and right heart function; it also provides perfusion studies and MR-based flow measurement to assess hemodynamic compromise. Ventilation studies have long been a domain of nuclear imaging, and new techniques for the direct visualization of ventilation are emerging from recent developments in the field of MR imaging, for example, using hyperpolarized inert gases. New functional parameters of ventilation can be derived from these studies. For the diagnosis of metabolically active disease, such as tumor and pneumonia, CT offers very high sensitivity, for example, in screening for intrapulmonary nodules using low-dose CT and in the early detection of pulmonary infiltrates in high-risk patients. Especially for characterizing pulmonary nodules there is a need to combine nuclear medicine techniques, such as in positron-emission tomography. (orig.) [de

Usefulness of pantomography in the diagnosis of facial skeletal diseases

International Nuclear Information System (INIS)

Rozylo, T.K.

1981-01-01

The use of pantomography for the diagnosis of pathological processes in the facial skeleton makes possible obtaining of radiological data rapidly on the film. The possibilities of pantomography application for the diagnosis of various diseases of this skeleton describing the advantages and disadvantages of the method and its usefulness in different stomatological disciplines are presented. (author)

Deep sequencing of the oral microbiome reveals signatures of periodontal disease.

Directory of Open Access Journals (Sweden)

Bo Liu

Full Text Available The oral microbiome, the complex ecosystem of microbes inhabiting the human mouth, harbors several thousands of bacterial types. The proliferation of pathogenic bacteria within the mouth gives rise to periodontitis, an inflammatory disease known to also constitute a risk factor for cardiovascular disease. While much is known about individual species associated with pathogenesis, the system-level mechanisms underlying the transition from health to disease are still poorly understood. Through the sequencing of the 16S rRNA gene and of whole community DNA we provide a glimpse at the global genetic, metabolic, and ecological changes associated with periodontitis in 15 subgingival plaque samples, four from each of two periodontitis patients, and the remaining samples from three healthy individuals. We also demonstrate the power of whole-metagenome sequencing approaches in characterizing the genomes of key players in the oral microbiome, including an unculturable TM7 organism. We reveal the disease microbiome to be enriched in virulence factors, and adapted to a parasitic lifestyle that takes advantage of the disrupted host homeostasis. Furthermore, diseased samples share a common structure that was not found in completely healthy samples, suggesting that the disease state may occupy a narrow region within the space of possible configurations of the oral microbiome. Our pilot study demonstrates the power of high-throughput sequencing as a tool for understanding the role of the oral microbiome in periodontal disease. Despite a modest level of sequencing (~2 lanes Illumina 76 bp PE and high human DNA contamination (up to ~90% we were able to partially reconstruct several oral microbes and to preliminarily characterize some systems-level differences between the healthy and diseased oral microbiomes.

Decision Support System for Hepatitis Disease Diagnosis using Bayesian Network

Directory of Open Access Journals (Sweden)

Shamshad Lakho

2017-12-01

Full Text Available Medical judgments are tough and challenging as the decisions are often based on the deficient and ambiguous information. Moreover, the result of decision process has direct effects on human lives. The act of human decision declines in emergency situations due to the complication, time limit, and high risks. Therefore, provision of medical diagnosis plays a dynamic role, specifically in the preliminary stage when a physician has limited diagnosis experience and identifies the directions to be taken for the treatment process. Computerized Decision Support Systems have brought a revolution in the medical diagnosis. These automatic systems support the diagnosticians in the course of diagnosis. The major role of Decision Support Systems is to support the medical personnel in decision-making procedures regarding disease diagnosis and treatment recommendation. The proposed system provides easy support in Hepatitis disease recognition. The system is developed using the Bayesian network model. The physician provides the input to the system in the form of symptoms stated by the patient. These signs and symptoms match with the casual relationships present in the knowledge model. The Bayesian network infers conclusion from the knowledge model and calculates the probability of occurrence of Hepatitis B, C and D disorders.

Live births after simultaneous avoidance of monogenic diseases and chromosome abnormality by next-generation sequencing with linkage analyses.

Science.gov (United States)

Yan, Liying; Huang, Lei; Xu, Liya; Huang, Jin; Ma, Fei; Zhu, Xiaohui; Tang, Yaqiong; Liu, Mingshan; Lian, Ying; Liu, Ping; Li, Rong; Lu, Sijia; Tang, Fuchou; Qiao, Jie; Xie, X Sunney

2015-12-29

In vitro fertilization (IVF), preimplantation genetic diagnosis (PGD), and preimplantation genetic screening (PGS) help patients to select embryos free of monogenic diseases and aneuploidy (chromosome abnormality). Next-generation sequencing (NGS) methods, while experiencing a rapid cost reduction, have improved the precision of PGD/PGS. However, the precision of PGD has been limited by the false-positive and false-negative single-nucleotide variations (SNVs), which are not acceptable in IVF and can be circumvented by linkage analyses, such as short tandem repeats or karyomapping. It is noteworthy that existing methods of detecting SNV/copy number variation (CNV) and linkage analysis often require separate procedures for the same embryo. Here we report an NGS-based PGD/PGS procedure that can simultaneously detect a single-gene disorder and aneuploidy and is capable of linkage analysis in a cost-effective way. This method, called "mutated allele revealed by sequencing with aneuploidy and linkage analyses" (MARSALA), involves multiple annealing and looping-based amplification cycles (MALBAC) for single-cell whole-genome amplification. Aneuploidy is determined by CNVs, whereas SNVs associated with the monogenic diseases are detected by PCR amplification of the MALBAC product. The false-positive and -negative SNVs are avoided by an NGS-based linkage analysis. Two healthy babies, free of the monogenic diseases of their parents, were born after such embryo selection. The monogenic diseases originated from a single base mutation on the autosome and the X-chromosome of the disease-carrying father and mother, respectively.

Diagnosis of coronary artery disease

International Nuclear Information System (INIS)

Pfisterer, M.; Gordon, D.; Battler, A.; Ashburn, W.; Froelicher, V.; Kantonsspital Basel

1979-01-01

In order to compare the three non-invasive exercise tests Ecg, Thallium myocardial perfusion imaging and radionuclide angiography in the diagnosis of coronary artery disease, the results of these tests in a consecutive series of 30 patients and 14 controls were analyzed. In all 88 symptom-limited exercise tests a significantly higher double product (heart rate x systolic blood pressure, mm Hg/min) was reached on a treadmill test (for Ecg and Thallium scintigraphy) as compared to the supine bicycle ergometer exercise (for radionuclide angiography): 243.1 +- 61.1 vs. 215.2 +- 46.5 x 10 2 (p [de

ETIOLOGY, PATHOGENESIS AND CLINICAL DIAGNOSIS OF PEYRONIE’S DISEASE

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Тарас Валерьевич Шатылко

2017-03-01

Full Text Available Peyronie’s disease remains an understudied progressing disease being  one of the relevant problems of modern urology and andrology. This condition may cause erectile dysfunction in men of fertile age and its negative impact on sexual function adversely affects patients’ quality of life. This article reviews epidemiology, pathophysiology and specifics of recording history and clinical diagnosis of Peyronie’s disease, that includes questionnaires, physical examination, evaluation of erectile function and penile deformity.

Exome sequencing and the management of neurometabolic disorders

OpenAIRE

Tarailo-Graovac, Maja; Shyr, Casper; Ross, Colin J; Horvath, Gabriella A; Salvarinova, Ramona; Ye, Xin C; Zhang, Lin-Hua; Bhavsar, Amit P; Lee, Jessica J Y; Drögemöller, Britt I; Abdelsayed, Mena; Alfadhel, Majid; Armstrong, Linlea; Baumgartner, Matthias R; Burda, Patricie

2016-01-01

BACKGROUND: Whole-exome sequencing has transformed gene discovery and diagnosis in rare diseases. Translation into disease-modifying treatments is challenging, particularly for intellectual developmental disorder. However, the exception is inborn errors of metabolism, since many of these disorders are responsive to therapy that targets pathophysiological features at the molecular or cellular level. METHODS: To uncover the genetic basis of potentially treatable inborn errors of metabolism, ...

Exome Sequencing and the Management of Neurometabolic Disorders

OpenAIRE

Tarailo-Graovac, Maja; Shyr, Casper; Ross, Colin J; Horvath, Gabriella A; Salvarinova, Ramona; Ye, Xin C; Zhang, Lin-Hua; Bhavsar, Amit P; Lee, Jessica J Y; Drögemöller, Britt I; Abdelsayed, Mena; Alfadhel, Majid; Armstrong, Linlea; Baumgartner, Matthias R; Burda, Patricie

2016-01-01

BACKGROUND: Whole-exome sequencing has transformed gene discovery and diagnosis in rare diseases. Translation into disease-modifying treatments is challenging, particularly for intellectual developmental disorder. However, the exception is inborn errors of metabolism, since many of these disorders are responsive to therapy that targets pathophysiological features at the molecular or cellular level.METHODS: To uncover the genetic basis of potentially treatable inborn errors of metabolism, we c...

To Know or Not to Know: Ethical Issues Related to Early Diagnosis of Alzheimer's Disease

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Niklas Mattsson

2010-01-01

Full Text Available In Alzheimer's disease (AD, pathological processes start in the brain long before clinical dementia. Biomarkers reflecting brain alterations may therefore indicate disease at an early stage, enabling early diagnosis. This raises several ethical questions and the potential benefits of early diagnosis must be weighted against possible disadvantages. Currently, there are few strong arguments favouring early diagnosis, due to the lack of disease modifying therapy. Also, available diagnostic methods risk erroneous classifications, with potentially grave consequences. However, a possible benefit of early diagnosis even without disease modifying therapy is that it may enable early decision making when patients still have full decision competence, avoiding problems of hypothetical consents. It may also help identifying patients with cognitive dysfunction secondary to other diseases that may be responsive to treatment already today.

A critical appraisal of advances in the diagnosis of diverticular disease.

Science.gov (United States)

Tursi, Antonio

2018-06-19

Diverticulosis of the colon is a common condition, and about one-fourth of those people develop symptoms, which is called 'diverticular disease' (DD). Since there are still some concerns about the diagnosis of DD, the aim of this review was to analyze current and evolving advances in its diagnosis. Area covered: Analysis of clinical, radiology, laboratory, and endoscopic tools to pose a correct diagnosis of DD was performed according to current PubMed literature. Expert commentary: A combination of clinical characteristic of the abdominal pain and fecal calprotectin expression may help to differentiate between symptomatic uncomplicated diverticular disease and irritable bowel syndrome. Abdominal computerized tomography (CT) scan is still the gold standard in diagnosing acute diverticulitis and its complications. CT-colonography may be useful as a predicting tool on the outcome of the disease. Diverticular Inflammation and Complications Assessment (DICA) endoscopic classification shows a significant relationship between severity of DICA score inflammatory indexes, as well as with severity of abdominal pain. Moreover, it seems to be predictive of the outcome of the disease in terms of acute diverticulitis occurrence/recurrence and surgery occurrence. Finally, preliminary data found intestinal microbiota analysis is a promising tool in diagnosing and monitoring this disease.

Massively parallel sequencing, aCGH, and RNA-Seq technologies provide a comprehensive molecular diagnosis of Fanconi anemia.

Science.gov (United States)

Chandrasekharappa, Settara C; Lach, Francis P; Kimble, Danielle C; Kamat, Aparna; Teer, Jamie K; Donovan, Frank X; Flynn, Elizabeth; Sen, Shurjo K; Thongthip, Supawat; Sanborn, Erica; Smogorzewska, Agata; Auerbach, Arleen D; Ostrander, Elaine A

2013-05-30

Current methods for detecting mutations in Fanconi anemia (FA)-suspected patients are inefficient and often miss mutations. We have applied recent advances in DNA sequencing and genomic capture to the diagnosis of FA. Specifically, we used custom molecular inversion probes or TruSeq-enrichment oligos to capture and sequence FA and related genes, including introns, from 27 samples from the International Fanconi Anemia Registry at The Rockefeller University. DNA sequencing was complemented with custom array comparative genomic hybridization (aCGH) and RNA sequencing (RNA-seq) analysis. aCGH identified deletions/duplications in 4 different FA genes. RNA-seq analysis revealed lack of allele specific expression associated with a deletion and splicing defects caused by missense, synonymous, and deep-in-intron variants. The combination of TruSeq-targeted capture, aCGH, and RNA-seq enabled us to identify the complementation group and biallelic germline mutations in all 27 families: FANCA (7), FANCB (3), FANCC (3), FANCD1 (1), FANCD2 (3), FANCF (2), FANCG (2), FANCI (1), FANCJ (2), and FANCL (3). FANCC mutations are often the cause of FA in patients of Ashkenazi Jewish (AJ) ancestry, and we identified 2 novel FANCC mutations in 2 patients of AJ ancestry. We describe here a strategy for efficient molecular diagnosis of FA.

Inflammatory bowel disease in Nigerians: Still a rare diagnosis?

African Journals Online (AJOL)

2011-06-15

Jun 15, 2011 ... immune to this affliction. Keywords: Inflammatory bowel disease, awareness, diagnosis, Nigerians .... anemia, mild leukocytosis, mild hypokalemia and. Ukwenya, et al. ... of four children but her last four pregnancies ended.

A Bibliographical Research of the Correlation Among Sasang Constitutional Disease and the Pulse Diagnosis

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Kim Dong-jun

2003-06-01

Full Text Available The purpose of this research was to investigate the correlation Among Sasang Constitutional Disease and Examination of the pulse. I have gone over literatures of mainly 「Dongyi Soose Bowon」and the others Oriental Medical book was studied about the Pulse Diagnosis. And then I came to get some conclusion as follows. 1. Soeumin(소음인 the initial-stage symptoms of wulkwang disease(울광증; when the Superficial Pulse and the Superficial+Moderate Pulse is made a diagnosis, Ceongunggyegitang(천궁계지탕 and Gunggyuhyangsosan(궁귀향소산 can be used. 2. Soeumin(소음인 the initial-stage blood disease symptoms of wulkwang disease(울광증; when the Minute+deep Pulse is made a diagnosis, Palmulgunjatang(팔물군자탕 and Guakhyanggeonggisan(곽향정기산 can be used. 3. Soeumin(소음인 the initial-stage symptoms of mangyang disease(망양증; when the Yang region Superficial Pulse and the Yin region Weak Pulse is made a diagnosis, Hwanggigyegitang(황기계지탕, Bojungikgitang(보중익기탕 and Sengyangikgitang(승양익기탕 can be used. 4. Soeumin(소음인 the symptoms of taeum disease(태음증; when the Minute Pulse and Deep+Thin Pulse is made a diagnosis, Sasang Prescription can be used. 5. Soeumin(소음인 the symptoms of soeum disease(소음증; when the Minute+Thin Pulse, Deep Pulse and Thin+Deep+Rapid Pulse is made a diagnosis, Sasang Prescription can be used. 6. Soyangin(소양인 Wind of soyang disease(소양상풍증; when the Superficial+Tight Pulse is made a diagnosis, Hungbangpaedogsan(형방패독산 can be used. And when the Deep+Full with strong power Pulse is made a diagnosis, Hyungbangdojeoksan(형방도적산 can be used. 7. Soyangin(소양인 the symptoms of mangyeum disease(망음증; when the Superficial+Large+Rapid Pulse and Flood+Large Pulse is made a diagnosis, Hungbangsabaeksan(형방사백산 can be used. And when the Wiry+Thin Pulse is made a diagnosis, Hungbanggiwhangtang(형방지황탕 can

Fuzzy cluster means algorithm for the diagnosis of confusable disease

African Journals Online (AJOL)

... end platform while Microsoft Access was used as the database application. The system gives a measure of each disease within a set of confusable disease. The proposed system had a classification accuracy of 60%. Keywords: Artificial Intelligence, expert system Fuzzy cluster – means Algorithm, physician, Diagnosis ...

Diseases of the small bowel in chronic diarrhea: diagnosis and treatment

Directory of Open Access Journals (Sweden)

M. Simadibrata

2002-09-01

Full Text Available The incidence of chronic diarrhea in Asia is between 0.8-1.0%. The diseases and abnormalities according to the location, which can cause chronic diarrhea, are divided into three locations: the small bowel, the large bowel and extraintestinal. The small bowel diseases include infectious and non-infectious diseases. The infectious diseases are bacterial infections, parasitic infections etc. The non-infectious diseases include of Crohn’s disease, Celiac sprue, NSAID enteropathy, lactose intolerance, benign tumor, carcinoid tumor, carcinoma, post surgery complications, laxative etc. The approaches to diagnosis include good anamnesis, careful physical examination, supporting laboratory tests, more specialized supporting examinations including X-ray of the colon, esophagogastroduodenum follow-through, enteroclysis, ileo-colonoscopy and endoscopy on the upper portion of the digestive tract including the small intestine with biopsy for histopathology examinations. The treatment for chronic diarrhea is divided into supportive and causal therapy. (Med J Indones 2002; 11: 179-89 Keywords: small bowel, chronic diarrhea, approaches to diagnosis, treatment

Prion diseases of the brain; Prionenerkrankung des Gehirns

Energy Technology Data Exchange (ETDEWEB)

Lutz, Kira; Urbach, Horst [Universitaetsklinik Freiburg (Germany). Klinik fuer Neuroradiologie

2015-09-15

The prion diseases of the brain, especially Creutzfeldt-Jakob disease, are rare fatal neurodegenerative disorders. A definitive CJD diagnosis is currently only possible by a brain biopsy or post mortem autopsy. The diagnosis of Creutzfeldt-Jakob disease is based on clinical signs, pathognomonic EEG, on typical MRI findings and the examination of the cerebrospinal fluid. Using the MRI the diagnosis Creutzfeldt-Jakob disease can be confirmed or excluded with high certainty. The MRI examination should contain diffusion-weighted and FLAIR imaging sequences. This review article provides an overview of the prion diseases of the brain with the corresponding imaging findings.

Serum Fragments of Tau for the Differential Diagnosis of Alzheimer's Disease

DEFF Research Database (Denmark)

Inekci, Dilek; Henriksen, K.; Linemann, T.

2015-01-01

Differential diagnosis of AD is still a challenge due to overlapping features with other types of dementia. Biomarkers for the differential diagnosis of AD can improve the diagnostic value of the disease and ensure an appropriate treatment of patients. The aim of this study was to evaluate...

PYOMYOSITIS IN SICKLE-CELL DISEASE - AN UNEXPECTED DIAGNOSIS

NARCIS (Netherlands)

SMID, WM; BREUKELMAN, F; KONINGS, JG; DAENEN, S

Pyomyositis is a pyogenic infection of muscle, leading to abscess formation. Pyomyositis is frequent in tropical areas but uncommon in areas with a temperate climate [4]; therefore, diagnosis can be difficult and can be delayed [6]. Sickle cell disease (SCD) can be complicated by vascular occlusion

Identifying patterns in signs and symptoms preceding the clinical diagnosis of Alzheimer's disease: Retrospective medical record review study and a nested case -control design.

Science.gov (United States)

Bature, Fidelia; Pang, Dong; Robinson, Anthea; Polson, Norma; Pappas, Yannis; Guinn, Barbara

2018-04-04

Evidence suggests that individuals with Alzheimer's disease (AD) are often diagnosed in the later stages of their disease with a poor prognosis. This study aimed to identify patterns in signs and symptoms preceding the clinical diagnosis of AD to suggest a predictive model for earlier diagnosis of the disease in the primary care. A retrospective medical record review; nested case control design. Participants included one hundred and nine patients from three general practice (GP) surgeries in Milton Keynes and Luton Clinical Commissioning groups (CCG) (37 cases with AD and 72 controls without AD). A retrospective analysis using the logistic regression of the presence of signs and symptoms before the diagnosis of AD was attained. Identification of the timing and sequence of appearance of these presentations as first reported before the clinical diagnosis was measured. Episodic memory with an odds ratio of 1.85 was the most frequent presentation, documented in 1.38% of the controls and 75.6% in cases. Auditory disturbance with an odds ratio of 3.03, which has not previously been noted except in the form of auditory hallucination, could have a diagnostic value. Auditory disturbance, which occurred mostly in the Caucasian females, could discriminate individuals with AD from those without. The symptom, which presented up to 14.5 (mean time) years prior to clinical diagnosis, was identified in Caucasians and mixed race individuals only. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Medical audit of rectal biopsy diagnosis of inflammatory bowel disease.

Science.gov (United States)

Frei, J V; Morson, B C

1982-03-01

The records of the rectal biopsy diagnoses of ulcerative colitis and Crohn's disease in the Department of Pathology, St Mark's Hospital, London, were reviewed. The biopsy diagnoses were compared to subsequent resection diagnoses on the same patients, and annual and seasonal variations in the frequency of these and related diagnoses were studied. The accuracy rate for the biopsy diagnosis of ulcerative colitis was about 70% and for Crohn's disease about 40% each time a biopsy was read. The low figure for the accuracy rate for Crohn's disease could be attributed to sampling error inherent in the diagnosis of a disease which is essentially patchy, showing discontinuous pathology. Also, many patients with Crohn's disease have a normal rectum which is biopsied to demonstrate the distinction from ulcerative colitis. In practical terms therefore a 40% accuracy rate in Crohn's disease is probably adequate. The rate of "false-positive" diagnoses was about 5%. There was a seasonal variation in the frequency of these two diagnoses, but no variation attributable to changes in observers, as pathology trainees in the Department change regularly. The frequency of diagnoses of non-specific inflammation and of normal colon did show such non-random variations.

Parkinson's Disease: New Research Offers Hope for Better Diagnosis and Treatments

Science.gov (United States)

... of this page please turn JavaScript on. Feature: Parkinson's Disease New Research Offers Hope for Better Diagnosis ... As many as one million Americans live with Parkinson's disease (PD), which is more than the combined ...

Artificial intelligence in diagnosis of obstructive lung disease: current status and future potential.

Science.gov (United States)

Das, Nilakash; Topalovic, Marko; Janssens, Wim

2018-03-01

The application of artificial intelligence in the diagnosis of obstructive lung diseases is an exciting phenomenon. Artificial intelligence algorithms work by finding patterns in data obtained from diagnostic tests, which can be used to predict clinical outcomes or to detect obstructive phenotypes. The purpose of this review is to describe the latest trends and to discuss the future potential of artificial intelligence in the diagnosis of obstructive lung diseases. Machine learning has been successfully used in automated interpretation of pulmonary function tests for differential diagnosis of obstructive lung diseases. Deep learning models such as convolutional neural network are state-of-the art for obstructive pattern recognition in computed tomography. Machine learning has also been applied in other diagnostic approaches such as forced oscillation test, breath analysis, lung sound analysis and telemedicine with promising results in small-scale studies. Overall, the application of artificial intelligence has produced encouraging results in the diagnosis of obstructive lung diseases. However, large-scale studies are still required to validate current findings and to boost its adoption by the medical community.

Cystic lung disease: Achieving a radiologic diagnosis

Energy Technology Data Exchange (ETDEWEB)

Trotman-Dickenson, Beatrice, E-mail: btrotmandickenson@partners.org

2014-01-15

Diffuse cystic lung disease represents a diverse group of uncommon disorders with characteristic appearance on high resolution CT imaging. The combination of imaging appearance with clinical features and genetic testing where appropriate permits a confident and accurate diagnosis in the majority of the diseases without recourse for open lung biopsy. The mechanism of cyst development disease is unclear but in some disorders appears to be related to small airways obstruction. These diseases are incurable, with the exception of Langerhans cell histiocytosis which may spontaneously remit or resolve on smoking cessation. Disease progression is unpredictable; in general older patients have a more benign disease, while young patients may progress rapidly to respiratory failure. An understanding of the complications of cystic lung disease and the appearance of disease progression is essential for the management of these patients. A number of these disorders are associated with malignancy, recognition of the potential tumors permits appropriate imaging surveillance. Due to the widespread use of CT, pulmonary cysts are increasingly discovered incidentally in an asymptomatic individual. The diagnostic challenge is to determine whether these cysts represent an early feature of a progressive disease or have no clinical significance. In the elderly population the cysts are unlikely to represent a progressive disease. In individuals <50 years further evaluation is recommended.

Cystic lung disease: Achieving a radiologic diagnosis

International Nuclear Information System (INIS)

Trotman-Dickenson, Beatrice

2014-01-01

Diffuse cystic lung disease represents a diverse group of uncommon disorders with characteristic appearance on high resolution CT imaging. The combination of imaging appearance with clinical features and genetic testing where appropriate permits a confident and accurate diagnosis in the majority of the diseases without recourse for open lung biopsy. The mechanism of cyst development disease is unclear but in some disorders appears to be related to small airways obstruction. These diseases are incurable, with the exception of Langerhans cell histiocytosis which may spontaneously remit or resolve on smoking cessation. Disease progression is unpredictable; in general older patients have a more benign disease, while young patients may progress rapidly to respiratory failure. An understanding of the complications of cystic lung disease and the appearance of disease progression is essential for the management of these patients. A number of these disorders are associated with malignancy, recognition of the potential tumors permits appropriate imaging surveillance. Due to the widespread use of CT, pulmonary cysts are increasingly discovered incidentally in an asymptomatic individual. The diagnostic challenge is to determine whether these cysts represent an early feature of a progressive disease or have no clinical significance. In the elderly population the cysts are unlikely to represent a progressive disease. In individuals <50 years further evaluation is recommended

Integrated Knowledge Based Expert System for Disease Diagnosis System

Science.gov (United States)

Arbaiy, Nureize; Sulaiman, Shafiza Eliza; Hassan, Norlida; Afizah Afip, Zehan

2017-08-01

The role and importance of healthcare systems to improve quality of life and social welfare in a society have been well recognized. Attention should be given to raise awareness and implementing appropriate measures to improve health care. Therefore, a computer based system is developed to serve as an alternative for people to self-diagnose their health status based on given symptoms. This strategy should be emphasized so that people can utilize the information correctly as a reference to enjoy healthier life. Hence, a Web-based Community Center for Healthcare Diagnosis system is developed based on expert system technique. Expert system reasoning technique is employed in the system to enable information about treatment and prevention of the diseases based on given symptoms. At present, three diseases are included which are arthritis, thalassemia and pneumococcal. Sets of rule and fact are managed in the knowledge based system. Web based technology is used as a platform to disseminate the information to users in order for them to optimize the information appropriately. This system will benefit people who wish to increase health awareness and seek expert knowledge on the diseases by performing self-diagnosis for early disease detection.

LSTM for diagnosis of neurodegenerative diseases using gait data

Science.gov (United States)

Zhao, Aite; Qi, Lin; Li, Jie; Dong, Junyu; Yu, Hui

2018-04-01

Neurodegenerative diseases (NDs) usually cause gait disorders and postural disorders, which provides an important basis for NDs diagnosis. By observing and analyzing these clinical manifestations, medical specialists finally give diagnostic results to the patient, which is inefficient and can be easily affected by doctors' subjectivity. In this paper, we propose a two-layer Long Short-Term Memory (LSTM) model to learn the gait patterns exhibited in the three NDs. The model was trained and tested using temporal data that was recorded by force-sensitive resistors including time series, such as stride interval and swing interval. Our proposed method outperforms other methods in literature in accordance with accuracy of the predicted diagnostic result. Our approach aims at providing the quantitative assessment so that to indicate the diagnosis and treatment of these neurodegenerative diseases in clinic

Flow cytometry of duodenal intraepithelial lymphocytes improves diagnosis of celiac disease in difficult cases.

Science.gov (United States)

Valle, Julio; Morgado, José Mario T; Ruiz-Martín, Juan; Guardiola, Antonio; Lopes-Nogueras, Miriam; García-Vela, Almudena; Martín-Sacristán, Beatriz; Sánchez-Muñoz, Laura

2017-10-01

Diagnosis of celiac disease is difficult when the combined results of serology and histology are inconclusive. Studies using flow cytometry of intraepithelial lymphocytes (IELs) have found that celiac patients have increased numbers of γδ IELs, along with a decrease in CD3-CD103 + IELs. The objective of this article is to assess the role of flow cytometric analysis of IELs in the diagnosis of celiac disease in difficult cases. A total of 312 patients with suspicion of celiac disease were included in the study. Duodenal biopsy samples were used for histological assessment and for flow cytometric analysis of IELs. In 46 out of 312 cases (14.7%) the combination of serology and histology did not allow the confirmation or exclusion of celiac disease. HLA typing had been performed in 42 of these difficult cases. Taking into account HLA typing and the response to a gluten-free diet, celiac disease was excluded in 30 of these cases and confirmed in the remaining 12. Flow cytometric analysis of IELs allowed a correct diagnosis in 39 out of 42 difficult cases (92.8%) and had a sensitivity of 91.7% (95% CI: 61.5% to 99.8%) and a specificity of 93.3% (95% CI: 77.9% to 99.2%) for the diagnosis of celiac disease in this setting. Flow cytometric analysis of IELs is useful for the diagnosis of celiac disease in difficult cases.

Exhaled nitric oxide in diagnosis and management of respiratory diseases

Directory of Open Access Journals (Sweden)

Abba Abdullah

2009-01-01

Full Text Available The analysis of biomarkers in exhaled breath constituents has recently become of great interest in the diagnosis, treatment and monitoring of many respiratory conditions. Of particular interest is the measurement of fractional exhaled nitric oxide (FENO in breath. Its measurement is noninvasive, easy and reproducible. The technique has recently been standardized by both American Thoracic Society and European Respiratory Society. The availability of cheap, portable and reliable equipment has made the assay possible in clinics by general physicians and, in the near future, at home by patients. The concentration of exhaled nitric oxide is markedly elevated in bronchial asthma and is positively related to the degree of esinophilic inflammation. Its measurement can be used in the diagnosis of bronchial asthma and titration of dose of steroids as well as to identify steroid responsive patients in chronic obstructive pulmonary disease. In primary ciliary dyskinesia, nasal NO is diagnostically low and of considerable value in diagnosis. Among lung transplant recipients, FENO can be of great value in the early detection of infection, bronchioloitis obliterans syndrome and rejection. This review discusses the biology, factors affecting measurement, and clinical application of FENO in the diagnosis and management of respiratory diseases.

Raman Spectroscopy: An Emerging Tool in Neurodegenerative Disease Research and Diagnosis.

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Devitt, George; Howard, Kelly; Mudher, Amrit; Mahajan, Sumeet

2018-03-21

The pathogenesis underlining many neurodegenerative diseases remains incompletely understood. The lack of effective biomarkers and disease preventative medicine demands the development of new techniques to efficiently probe the mechanisms of disease and to detect early biomarkers predictive of disease onset. Raman spectroscopy is an established technique that allows the label-free fingerprinting and imaging of molecules based on their chemical constitution and structure. While analysis of isolated biological molecules has been widespread in the chemical community, applications of Raman spectroscopy to study clinically relevant biological species, disease pathogenesis, and diagnosis have been rapidly increasing since the past decade. The growing number of biomedical applications has shown the potential of Raman spectroscopy for detection of novel biomarkers that could enable the rapid and accurate screening of disease susceptibility and onset. Here we provide an overview of Raman spectroscopy and related techniques and their application to neurodegenerative diseases. We further discuss their potential utility in research, biomarker detection, and diagnosis. Challenges to routine use of Raman spectroscopy in the context of neuroscience research are also presented.

Artificial intelligence aiding the thin-section CT diagnosis of diffuse pulmonary diseases

International Nuclear Information System (INIS)

Han, Dae Hee; Koh, Young Hwan; Seong, Chang Kyu; Kim, Ji Hoon; Choi, Young Ho; Kim, Jong Hyo; Chae, Young Moon; Lee, Yun Hee; Han, Heon

2006-01-01

We wanted to develop and test an artificial intelligence (AI) to assist physicians in making the thin-section CT diagnosis of diffuse pulmonary diseases. The AI was composed of knowledge bases (KB) of 12 diffuse pulmonary diseases and an inference engine (IE). The KB of a disease included both the inclusion criteria (IC) and the exclusion criteria (EC), which were the clinical or thin-section CT findings that were known to be present or absent in that particular disease, respectively. From imputing the clinical or thin-section CT findings by the operator who was reading the thin-section CT, AI instantly executed the following two steps. First, the IE eliminated all diseases from the list which the EC had for those particular findings. Next, from a list or remaining diseases, the AI selected those diseases having those findings in its IC to formulate the 1st-step differential diagnosis (DD1). For the differential diagnosis in the next step, the reader could choose one more clinical or thin-section CT finding from the new list: [(all the findings in the IC or EC of DD1)-(the findings in the IC common to all the DD1s)]. The reader could proceed even further if needed. The system was tested on 10 radiology residents who solved 24 problems (two problems for each of 12 diffuse pulmonary diseases) without and then with the aid of the AI. The scores were compared using the Wilcoxon signed rank test. An AI was made; it was composed of 280 rules (214 IC and 66 EC) and there interfaces (two for program management and another for problem solving). Contestants scored higher (ρ = 0.0078) using the AI (167 vs. 110 respectively), and they responded that they felt that the program was helpful in making decisions. AI appeared to be helpful in making thin-section CT diagnosis

Artificial intelligence aiding the thin-section CT diagnosis of diffuse pulmonary diseases

Energy Technology Data Exchange (ETDEWEB)

Han, Dae Hee; Koh, Young Hwan; Seong, Chang Kyu; Kim, Ji Hoon; Choi, Young Ho [Boramae Munincipal Hospital, Seoul National University College of Medicine, Seoul (Korea, Republic of); Kim, Jong Hyo [Seoul National University College of Medicine, Seoul (Korea, Republic of); Chae, Young Moon [Yonsei University Graduate School of Public Heath, Seoul (Korea, Republic of); Lee, Yun Hee [The Graduate School of Imformation, Yonsei, Seoul (Korea, Republic of); Han, Heon [Kangwon National University College of Medicine, Chuncheon (Korea, Republic of)

2006-06-15

We wanted to develop and test an artificial intelligence (AI) to assist physicians in making the thin-section CT diagnosis of diffuse pulmonary diseases. The AI was composed of knowledge bases (KB) of 12 diffuse pulmonary diseases and an inference engine (IE). The KB of a disease included both the inclusion criteria (IC) and the exclusion criteria (EC), which were the clinical or thin-section CT findings that were known to be present or absent in that particular disease, respectively. From imputing the clinical or thin-section CT findings by the operator who was reading the thin-section CT, AI instantly executed the following two steps. First, the IE eliminated all diseases from the list which the EC had for those particular findings. Next, from a list or remaining diseases, the AI selected those diseases having those findings in its IC to formulate the 1st-step differential diagnosis (DD1). For the differential diagnosis in the next step, the reader could choose one more clinical or thin-section CT finding from the new list: [(all the findings in the IC or EC of DD1)-(the findings in the IC common to all the DD1s)]. The reader could proceed even further if needed. The system was tested on 10 radiology residents who solved 24 problems (two problems for each of 12 diffuse pulmonary diseases) without and then with the aid of the AI. The scores were compared using the Wilcoxon signed rank test. An AI was made; it was composed of 280 rules (214 IC and 66 EC) and there interfaces (two for program management and another for problem solving). Contestants scored higher ({rho} = 0.0078) using the AI (167 vs. 110 respectively), and they responded that they felt that the program was helpful in making decisions. AI appeared to be helpful in making thin-section CT diagnosis.

Sirenomelia sequence: early prenatal diagnosis of one rare case associated with acardiac malformation.

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Zanforlin Filho, Sebastião M; Guimarães Filho, Hélio A; Araujo Júnior, Edward; Pires, Cláudio R; Mattar, Rosiane; Nardozza, Luciano M M

2007-04-01

Sirenomelia sequence is a very rare congenital malformation, with incidence of around 1.5-4.2 per 100,000 births. Prenatal diagnosis of sirenomelia in the first trimester is rare; there are only five cases reported for the present, and the association of sirenomelia with acardiac malformation is even rarer. We present a rare case of sirenomelia associated with acardiac malformation detected in the first trimester through combined two-dimensional, three-dimensional and color Doppler sonographies.

Chitotriosidase activity as additional biomarker in the diagnosis of lysosomal storage diseases

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N. V. Olkhovych

2016-02-01

Full Text Available To date, several genetic variants that lead to a deficiency of chitotriosidase activity have been described. The duplication of 24 bp (dup24bp in exon 10 of the CHIT1 gene, which causes a complete loss of enzymatic activity of the gene product, is the most common among the European population. The aim of the study was to evaluate the possibility of using chitotriosidase activity as an additional biomarker in diagnosis of lysosomal storage diseases (LSDs in Ukraine, to determine this parameter in blood plasma of the patients with various lysosomal diseases and to assess the effect of the presence of dup24bp in the CHIT1 gene on this parameter. It has been shown that chitotriosidase activity in blood plasma is a convenient additional biochemical marker in the diagnosis of some LSDs, namely Gaucher disease, Niemann-Pick disease A, B, C and GM1-gangliosidosis. Reference ranges of the normal chitotriosidase activity were determined in blood plasma of Ukrainian population and found to be 8.0-53.1 nmol 4-methylumbelliferone/h·ml of plasma. The total allele frequency of the dup24bp in the CHIT1 gene in Ukrainian population was determined, which amounted to 0.26 (323/1244 that is higher than in European population. It was indicated that molecular-genetic screening of dup24bp in the CHIT1 gene is a necessary stage in a protocol for the laboratory diagnosis of Gaucher disease, Niemann-Pick disease A, B, C as well as GM1-gangliosidosis to avoid incorrect diagnosis.

Diagnosis and management of Pompe disease | Bhengu | South ...

African Journals Online (AJOL)

A multidisciplinary team approach to treatment of affected patients is optimum with, as team leader, a physician who has experience in managing this rare disorder. In this article, we present a brief overview of the disease and provide guidelines for diagnosis and management of this condition in South Africa.

Molecular Diagnosis of Tuberculosis.

Science.gov (United States)

Nurwidya, Fariz; Handayani, Diah; Burhan, Erlina; Yunus, Faisal

2018-01-01

Tuberculosis (TB) is one of the leading causes of adult death in the Asia-Pacific Region, including Indonesia. As an infectious disease caused by Mycobacterium tuberculosis (MTB), TB remains a major public health issue especially in developing nations due to the lack of adequate diagnostic testing facilities. Diagnosis of TB has entered an era of molecular detection that provides faster and more cost-effective methods to diagnose and confirm drug resistance in TB cases, meanwhile, diagnosis by conventional culture systems requires several weeks. New advances in the molecular detection of TB, including the faster and simpler nucleic acid amplification test (NAAT) and whole-genome sequencing (WGS), have resulted in a shorter time for diagnosis and, therefore, faster TB treatments. In this review, we explored the current findings on molecular diagnosis of TB and drug-resistant TB to see how this advancement could be integrated into public health systems in order to control TB.

Diagnosis and management of von Willebrand disease: guidelines for primary care.

Science.gov (United States)

Yawn, Barbara; Nichols, William L; Rick, Margaret E

2009-12-01

Von Willebrand disease is an inherited condition characterized by deficiency of von Willebrand factor, which is essential in hemostasis. The National Heart, Lung, and Blood Institute has released new evidence-based guidelines for the diagnosis and management of the disease. There are three major subtypes of von Willebrand disease, classified as partial quantitative deficiency (low levels) of von Willebrand factor (type 1), qualitative deficiency (type 2), or virtually complete deficiency (type 3). Diagnosis is usually made by reviewing the patient's personal and family history of bleeding and by clinical evaluation for more common reasons for bleeding, supplemented with laboratory tests. Assessment may be used to determine bleeding risk before surgery and other invasive procedures, and to diagnose reasons for unexplained hemorrhaging. Von Willebrand factor levels of 30 IU per dL or lower are required for the definite diagnosis of inherited von Willebrand disease. Persons with levels of 30 to 50 IU per dL may not have the disease, but may need agents to increase von Willebrand factor levels during invasive procedures or childbirth. Treatment is tailored to the subtype of the disease: increasing plasma concentration of von Willebrand factor by releasing endogenous stores with desmopressin or replacing nonexistent or ineffective von Willebrand factor by using human plasma-derived, viral-inactivated concentrates; treatment is often combined with hemostatic agents that have mechanisms other than increasing von Willebrand factor. Regular prophylaxis is seldom required, and treatment is initiated before planned invasive procedures or in response to bleeding.

Timely diagnosis of dairy calf respiratory disease using a standardized scoring system.

Science.gov (United States)

McGuirk, Sheila M; Peek, Simon F

2014-12-01

Respiratory disease of young dairy calves is a significant cause of morbidity, mortality, economic loss, and animal welfare concern but there is no gold standard diagnostic test for antemortem diagnosis. Clinical signs typically used to make a diagnosis of respiratory disease of calves are fever, cough, ocular or nasal discharge, abnormal breathing, and auscultation of abnormal lung sounds. Unfortunately, routine screening of calves for respiratory disease on the farm is rarely performed and until more comprehensive, practical and affordable respiratory disease-screening tools such as accelerometers, pedometers, appetite monitors, feed consumption detection systems, remote temperature recording devices, radiant heat detectors, electronic stethoscopes, and thoracic ultrasound are validated, timely diagnosis of respiratory disease can be facilitated using a standardized scoring system. We have developed a scoring system that attributes severity scores to each of four clinical parameters; rectal temperature, cough, nasal discharge, ocular discharge or ear position. A total respiratory score of five points or higher (provided that at least two abnormal parameters are observed) can be used to distinguish affected from unaffected calves. This can be applied as a screening tool twice-weekly to identify pre-weaned calves with respiratory disease thereby facilitating early detection. Coupled with effective treatment protocols, this scoring system will reduce post-weaning pneumonia, chronic pneumonia, and otitis media.

Investigation of the imaging diagnosis on the ophthalmic orbital diseases

International Nuclear Information System (INIS)

Yoshizawa, Toshikazu

1991-01-01

Ultrasonographic examination, X-ray computerized tomography (CT) and magnetic resonance imaging (MRI) were performed on orbital diseases. Ultrasonographic examination was a simple, rapid and harmless noninvasive precedure as a diagnostic tool for evaluation of soft tissues. Echography was not more precise than X-ray CT and MRI scan in orbital diagnosis of the localization, size and well-defined outline of the lesion, relating to the peri- and retroorbital organs, however, was useful for screening study of an orbital lesion. B-mode of orbital tumors was effective for the ultrasonic diagnosis and classification according to four types; solid, cystic, angiomatous and infiltrative patterns. B-scan study of intraorbital inflammatory pseudo tumor could provide a differential diagnosis between inflammatory edema and an inflammatory mass lesion. Echographic pictures of dural arterio-venous fistula disclosed the vascular dilatation of superior ophthalmic vein and those of Basedow's disease with thickening of extraocular muscles. X-ray CT revealed intraorbital and intraocular disease, the globes and its immediate surrounding tissue (optic nerve, extraocular muscle, etc.) and bony orbital walls as the same slice of film. X-ray CT pictures of a coronal section, the contrast enhancement, calcification and destruction of the bone were helpful for diagnosis. However, the displays of disorders near the bone were ill-defined because of an artifact induced by high X-ray absorptive power of the bone. MRI was an equipment for superior contrast resolution, with provided a tomography of any section, without artifacts of the bone, and was the superior technique for displaying a vascular lesion. MRI of orbital disease was effective for reconstructing the spatial correlations between the lesion and its surounding tissues. MRI, however, provided no information of the skeleton, being not available for subjects with a magnetic substance. (author)

Embryo genome profiling by single-cell sequencing for preimplantation genetic diagnosis in a β-thalassemia family

DEFF Research Database (Denmark)

Xu, Yanwen; Chen, Shengpei; Yin, Xuyang

2015-01-01

for a β-thalassemia-carrier couple to have a healthy second baby. We carried out sequencing for single blastomere cells and the family trio and further developed the analysis pipeline, including recovery of the missing alleles, removal of the majority of errors, and phasing of the embryonic genome...... leukocyte antigen matching tests. CONCLUSIONS: This retrospective study in a β-thalassemia family demonstrates a method for embryo genome recovery through single-cell sequencing, which permits detection of genetic variations in preimplantation genetic diagnosis. It shows the potential of single...

[Colonic diverticular disease: diagnosis and therapy].

Science.gov (United States)

Lakatos, László; Lakatos, Péter László

2012-02-12

Colonic diverticular disease is one of the most common gastrointestinal disorders in the Western world, affecting approximately 50% of the population above the age of 70 years. Symptoms develop only in about one quarter of the affected individuals with complications in one-third of the symptomatic patients. Diagnosis is mostly confirmed by colonoscopy. Abdominal CT is the most sensitive for the diagnosis of complicated severe diverticulitis, while colonoscopy or in severe cases angiography may be performed in bleeding patients. Initial therapy of non-complicated symptomatic diverticulitis includes antibiotics and more recently non-absorbable antibiotics. In complicated cases should be treated with broad spectrum i.v. antibiotics, however surgery may became necessary in a minority of the cases. The proportion of patients needing acute surgical intervention has decreased in the last decades with the advancement of conservative management including medical therapy, endoscopy and imaging techniques and the indication of elective was also changed.

Gestational Trophoblastic Disease: A Multimodality Imaging Approach with Impact on Diagnosis and Management

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Sunita Dhanda

2014-01-01

Full Text Available Gestational trophoblastic disease is a condition of uncertain etiology, comprised of hydatiform mole (complete and partial, invasive mole, choriocarcinoma, and placental site trophoblastic tumor. It arises from abnormal proliferation of trophoblastic tissue. Early diagnosis of gestational trophoblastic disease and its potential complications is important for timely and successful management of the condition with preservation of fertility. Initial diagnosis is based on a multimodality approach: encompassing clinical features, serial quantitative β-hCG titers, and pelvic ultrasonography. Pelvic magnetic resonance imaging (MRI is sometimes used as a problem-solving tool to assess the depth of myometrial invasion and extrauterine disease spread in equivocal and complicated cases. Chest radiography, body computed tomography (CT, and brain MRI have been recommended as investigative tools for overall disease staging. Angiography has a role in management of disease complications and metastases. Efficacy of PET (positron emission tomography and PET/CT in the evaluation of recurrent or metastatic disease has not been adequately investigated yet. This paper discusses the imaging features of gestational trophoblastic disease on various imaging modalities and the role of different imaging techniques in the diagnosis and management of this entity.

Intestinal lesions in pediatric Crohn disease: comparative detectability among pulse sequences at MR enterography

International Nuclear Information System (INIS)

Sohn, Beomseok; Kim, Myung-Joon; Lee, Mi-Jung; Koh, Hong; Han, Kyung Hwa

2014-01-01

Variable sequences can be used in MR enterography, and no consensus exists for the best protocol in children with Crohn disease. To compare the lesion detectability of various MR enterography sequences and to correlate the findings of these sequences with the Pediatric Crohn's Disease Activity Index (PCDAI) in children with Crohn disease. Children with clinically or pathologically confirmed Crohn disease underwent MR enterography, including a single-shot fast spin-echo (SSFSE) sequence, motility imaging (coronal 2-D balanced fast field echo), diffusion-weighted imaging (DWI), and dynamic contrast enhancement imaging (including arterial, portal and delayed phases). The lesion detectability of each sequence was graded 0-2 for each involved bowel segment. The lesion detectability and PCDAI result on different sequences were compared using the weighted least squares method and Student's t-test, respectively. Fifteen children (11 boys, 4 girls, mean age 13.7 ± 1.4 years) with a total of 41 lesions were included in this study. All lesions detected in more than two sequences were visible on the single-shot fast spin-echo (SSFSE) sequence. The relative lesion detection rate was 78.1% on motility imaging, 90.2% on DWI, and 92.7% on arterial, 95.1% on portal and 95.1% on delayed phase imaging. Compared to the SSFSE sequence, motility imaging (P < 0.001) and DWI (P = 0.039) demonstrated lower detectability. The mean PCDAI result in the detected lesions was statistically higher only on dynamic enhancement imaging (P < 0.001). All MR enterography sequences were found to have relatively high lesion detectability in children with Crohn disease, while motility imaging showed the lowest lesion detectability. Lesions detected on dynamic enhancement imaging showed a higher PCDAI result, which suggests that this sequence is specific for active inflammation. (orig.)

On the Problem of Differential Diagnosis of Inflammatory and Functional Bowel Diseases

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I.Ya. Budzak

2013-04-01

Full Text Available The paper describes the problems of differential diagnosis of inflammatory (ulcerative colitis, Crohn’s disease and functional (irritable bowel syndrome disease of the intestine. The necessity of such differential diagnosis in certain categories of patients was noted. The possibilities of instrumental and laboratory methods of study are shown. Particular attention is paid to the definition of fecal tests — calprotectin and lactoferrin. An analysis of the studies of their information content has been carried out.

An integrated diagnosis strategy for congenital myopathies.

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Johann Böhm

Full Text Available Congenital myopathies are severe muscle disorders affecting adults as well as children in all populations. The diagnosis of congenital myopathies is constrained by strong clinical and genetic heterogeneity. Moreover, the majority of patients present with unspecific histological features, precluding purposive molecular diagnosis and demonstrating the need for an alternative and more efficient diagnostic approach. We used exome sequencing complemented by histological and ultrastructural analysis of muscle biopsies to identify the causative mutations in eight patients with clinically different skeletal muscle pathologies, ranging from a fatal neonatal myopathy to a mild and slowly progressive myopathy with adult onset. We identified RYR1 (ryanodine receptor mutations in six patients and NEB (nebulin mutations in two patients. We found novel missense and nonsense mutations, unraveled small insertions/deletions and confirmed their impact on splicing and mRNA/protein stability. Histological and ultrastructural findings of the muscle biopsies of the patients validated the exome sequencing results. We provide the evidence that an integrated strategy combining exome sequencing with clinical and histopathological investigations overcomes the limitations of the individual approaches to allow a fast and efficient diagnosis, accelerating the patient's access to a better healthcare and disease management. This is of particular interest for the diagnosis of congenital myopathies, which involve very large genes like RYR1 and NEB as well as genetic and phenotypic heterogeneity.

Motor Sequence Learning Performance in Parkinson's Disease Patients Depends on the Stage of Disease

Science.gov (United States)

Stephan, Marianne A.; Meier, Beat; Zaugg, Sabine Weber; Kaelin-Lang, Alain

2011-01-01

It is still unclear, whether patients with Parkinson's disease (PD) are impaired in the incidental learning of different motor sequences in short succession, although such a deficit might greatly impact their daily life. The aim of this study was thus to clarify the relation between disease parameters of PD and incidental motor learning of two…

Artificial intelligence-assisted occupational lung disease diagnosis.

Science.gov (United States)

Harber, P; McCoy, J M; Howard, K; Greer, D; Luo, J

1991-08-01

An artificial intelligence expert-based system for facilitating the clinical recognition of occupational and environmental factors in lung disease has been developed in a pilot fashion. It utilizes a knowledge representation scheme to capture relevant clinical knowledge into structures about specific objects (jobs, diseases, etc) and pairwise relations between objects. Quantifiers describe both the closeness of association and risk, as well as the degree of belief in the validity of a fact. An independent inference engine utilizes the knowledge, combining likelihoods and uncertainties to achieve estimates of likelihood factors for specific paths from work to illness. The system creates a series of "paths," linking work activities to disease outcomes. One path links a single period of work to a single possible disease outcome. In a preliminary trial, the number of "paths" from job to possible disease averaged 18 per subject in a general population and averaged 25 per subject in an asthmatic population. Artificial intelligence methods hold promise in the future to facilitate diagnosis in pulmonary and occupational medicine.

The CDD system in computed tomographic diagnosis of diverticular disease

International Nuclear Information System (INIS)

Pustelnik, Daniel; Elsholtz, Fabian Henry Juergen; Hamm, Bernd; Niehues, Stefan Markus; Bojarski, Christian

2017-01-01

Purpose cation in computed tomographic diagnosis and briefly recapitulates its targeted advantages over preliminary systems. Primarily, application of the CDD in computed tomography diagnostics is described. Differences with respect to the categories of the older systems are pointed out on the level of each CDD type using imaging examples. The presented images are derived from our institute according to the S2k criteria. Literature was researched on PubMed. Results The CDD constitutes an improvement compared to older systems for categorizing the stages of diverticular disease. It provides more discriminatory power on the descriptive-morphological level and defines as well as differentiates more courses of the disease. Furthermore, the categories translate more directly into state-of-the-art decision-making concerning hospitalization and therapy. The CDD should be applied routinely in the computed tomographic diagnosis of diverticular disease. Typical imaging patterns are presented.

[Guidelines for the diagnosis and management of thyroid disease and their utility].

Science.gov (United States)

Hashimoto, Koshi; Mori, Masatomo

2012-11-01

Thyroid dysfunction is a common disorder in daily clinical practice, however due to unspecific and diverse symptoms of the disease, it is sometimes hard to make a definite diagnosis. Japan thyroid association (JTA) published 'Guideline for the diagnosis of thyroid disease, 2010' and it is open to the public on the JTA website(http : //www.japanthyroid.jp/doctor/ guideline/japanese.html). English version of the guideline is also available. JTA also published 'Guideline for the management of subclinical hypothyroidism 2008' and 'Guideline for the diagnosis of thyroid storm, version 2'. The latter in English version has been published in Thyroid(http : //www.ncbi.nlm.nih.gov/pubmed/22494618). The utility of these guidelines is discussed.

Preclinical diagnosis of Alzheimer's disease: Prevention or prediction?

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Ricardo Nitrini

Full Text Available Abstract The diagnosis of Alzheimer's disease (AD for cases with dementia may be too late to allow effective treatment. Criteria for diagnosis of preclinical AD suggested by the Alzheimer's Association include the use of molecular and structural biomarkers. Preclinical diagnosis will enable testing of new drugs and forms of treatment toward achieving successful preventive treatment. But what are the advantages for the individual? To know that someone who is cognitively normal is probably going to develop AD's dementia when there is no effective preventive treatment is definitely not good news. A research method whereby volunteers are assigned to receive treatment or placebo without knowing whether they are in the control or at-risk arm of a trial would overcome this potential problem. If these new criteria are used wisely they may represent a relevant milestone in the search for a definitive treatment for AD.

Molecular diagnosis in haemophilia A.

Directory of Open Access Journals (Sweden)

Pandey G

2001-10-01

Full Text Available Haemophilia A is the commonest cause of X-linked inherited bleeding disorder. Due to inadequate medical facility for management of the disease, the DNA based genetic diagnosis has assumed great importance. Ideally, the direct detection of mutations is the most accurate and reliable approach for carrier detection and prenatal diagnosis. However, mutation detection is possible only in limited number of cases. In majority of haemophiliacs, no common mutation is easily identifiable. The limitation has been over come by the use of linkage-based analysis using polymorphic DNA markers in the factor VIII gene. Some of these markers can be identified by restriction enzymes and are called RFLP markers. Other markers are a class of short tandem repeats sequences which result in differences in the number of CA repeats in different individuals. The combined use of these markers has made it possible to identify carriers and provide prenatal diagnosis in upto 95% of families having affected individuals. Therefore, the recurrence of the disease can be prevented to a great extent in the haemophilia A affected families.

Diverticular Disease and Colorectal Cancer: Incidental Diagnosis or Real Association? Final Answer.

Science.gov (United States)

Regula, Jaroslaw

2016-10-01

Associations between diverticular disease of the colon and the colorectal cancer has been studied for >60 years. Observational, cross-sectional, and case-control studies as well as large population-based studies gave conflicting results and association was not fully proven. Obtaining the proof was difficult because both diseases share similar clinical characteristics, both increase with age, and both involve similar dietary factors. Long-term observations are difficult as diagnostic methods changed over time from barium enema 50 to 60 years ago, through endoscopy, up to CT and MR in recent years. Cancer or adenomas may be missed within diverticular segment; diverticula may be underreported in patients with colon cancer diagnosis. Most recent 2 large cohort studies have solved the dilemma. These studies have clearly shown that diverticular disease does not increase the risk of colon cancer after the first year of diagnosis. Within the first year of diagnosis the association is strong, most probably due to difficulties with differential diagnosis and misclassifications and shared symptoms. Findings of these studies have led to the conclusion that colon cancer has to be excluded using modern techniques after the first episode of suspected diverticulitis.

Biomarkers in the early diagnosis of Parkinson's disease

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CHEN Sheng-di

2013-08-01

Full Text Available Parkinson's disease (PD is a chronic and progressive neurodegenerative disorder. It has become clear that PD can have a preclinical phase, a period during which neurodegeneration has already begun years before the onset of typical motor symptoms. Consequently, if the early neurodegeneration in PD can be timely diagnosed, it will significantly slow down the progression of the disease and improve the quality of life. To date, there is no fully reliable and validated biomarker for the early diagnosis of PD, but some promising biomarker candidates exist.

Maremar, prevalence of chronic kidney disease, how to avoid over-diagnosis and under-diagnosis.

Science.gov (United States)

De Broe, Marc E; Gharbi, Mohammed Benghanem; Elseviers, Monique

2016-04-01

Chronic kidney disease is considered as a major public health problem. Recent studies mention a prevalence rate between 8%-12%. Several editorials, comments, short reviews described the weaknesses (lack of confirmation of proteinuria, and of chronicity of decreased estimated glomerular filtration rate) of a substantial number of studies and the irrational of using a single arbitrary set point, i.e. diagnosis of chronic kidney disease whenever the estimated glomerular filtration rate is less than 60mL/min/1.73m(2). Maremar (Maladies rénales chroniques au Maroc) is a prevalence study of chronic kidney disease, hypertension, diabetes and obesity in a randomized, representative, high response rate (85%), sample of the adult population of Morocco, strictly applying the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Compared to the vast majority of the available studies, Maremar has a low prevalence of chronic kidney disease (2.9% adjusted to the actual adult population of Morocco). The population pyramid, and particularly the confirmation of proteinuria and "chronicity" of the decreased estimated glomerular filtration rate are the main reasons for this low prevalence of chronic kidney disease. The choice of arbitrary single threshold of estimated glomerular filtration rate for classifying stage 3-5 chronic kidney disease inevitably leads to "over-diagnosis" (false positives) of the disease in the elderly, particularly those without proteinuria, hematuria or hypertension, and to "under-diagnosed" (false negatives) in younger individuals with an estimated glomerular filtration rate above 60mL/min/1.73m(2) and below the 3rd percentile of their age/gender category. There is an urgent need for quality studies using in a correct way the recent KDIGO guidelines when investigating the prevalence of chronic kidney disease, in order to avoid a 50 to 100% overestimation of a disease state with potential dramatic consequences. The combination of the general population

Questions from the clinician to the radiologist regarding the diagnosis of metabolic bone diseases

Energy Technology Data Exchange (ETDEWEB)

Schulz, W.; Schmidt, M.

1986-12-01

Macromorphological X-ray findings in metabolic bone diseases can be established only in advanced stages. Micromorphological X-ray diagnostic procedures will support the diagnosis even in early stages. Mineralometric examinations are adjuvant methods for early diagnosis and survey of therapy in metabolic bone diseases. The synopsis of parameters of calcium phosphate metabolism, bone histology (histomorphometry) and radiological morphology enables the type and stage of osteopathy to be diagnosed. The supplementary diagnostic methods are helpful in distinguishing bone diseases with increased turnover, inpaired bone modelling and absorption, disturbed mineralization and ectopic calcification. Within the metabolic osteopathies, osteoporosis is gaining more and more importance as a socioeconomic problem; therefore, early diagnosis and treatment are of significant relevance. Hyper-, hypoparathyroidism and osteoidosis are diseases at can be cured if diagnosed early.

Questions from the clinician to the radiologist regarding the diagnosis of metabolic bone diseases

International Nuclear Information System (INIS)

Schulz, W.; Schmidt, M.; Klinikum Bamberg

1986-01-01

Macromorphological X-ray findings in metabolic bone diseases can be established only in advanced stages. Micromorphological X-ray diagnostic procedures will support the diagnosis even in early stages. Mineralometric examinations are adjuvant methods for early diagnosis and survey of therapy in metabolic bone diseases. The synopsis of parameters of calcium phosphate metabolism, bone histology (histomorphometry) and radiological morphology enables the type and stage of osteopathy to be diagnosed. The supplementary diagnostic methods are helpful in distinguishing bone diseases with increased turnover, inpaired bone modelling and absorption, disturbed mineralization and ectopic calcification. Within the metabolic osteopathies, osteoporosis is gaining more and more importance as a socioeconomic problem; therefore, early diagnosis and treatment are of significant relevance. Hyper-, hypoparathyroidism and osteoidosis are diseases at can be cured if diagnosed early. (orig.) [de

Advances in Diagnosis and Management of Celiac Disease

Science.gov (United States)

Kelly, Ciarán P.; Bai, Julio C.; Liu, Edwin; Leffler, Daniel A.

2015-01-01

Celiac disease is an autoimmune disorder induced by dietary gluten in genetically predisposed individuals. It has a prevalence of ∼1% in many populations worldwide. New diagnoses have increased substantially, due to increased awareness, better diagnostic tools, and probable, real increases in incidence. The breadth of recognized clinical presentations continues to expand, making the disorder highly relevant to all physicians. Newer diagnostic tools, including serologic tests for antibodies against tissue transglutaminase (tTG) and deamidated gliadin peptide, greatly facilitate diagnosis. Tests for celiac-permissive HLA DQ2 and DQ8 molecules are useful in defined clinical situations. Celiac disease is diagnosed by histopathologic examination of duodenal biopsies. However, according to recent controversial guidelines, a diagnosis can be made without biopsy in certain circumstances, especially for children. Symptoms, mortality, and risk for malignancy can each be reduced by adherence to a gluten-free diet. This treatment is a challenge, however, as the diet is expensive, socially isolating, and not always effective in controlling symptoms or intestinal damage. Hence, there is increasing interest in developing non-dietary therapies. PMID:25662623

AMERICAN COLLEGE OF GASTROENTEROLOGY CLINICAL GUIDELINE: DIAGNOSIS AND MANAGEMENT OF CELIAC DISEASE

Science.gov (United States)

Rubio-Tapia, Alberto; Hill, Ivor D; Kelly, Ciarán P; Calderwood, Audrey H; Murray, Joseph A

2013-01-01

This guideline presents recommendations for the diagnosis and management of patients with celiac disease. Celiac disease is an immune-based reaction to dietary gluten (storage protein for wheat, barley and rye) that primarily affects the small intestine in those with a genetic predisposition and resolves with exclusion of gluten from the diet. There has been a substantial increase in the prevalence of celiac disease over the last 50 years and an increase in the rate of diagnosis in the last 10 years. Celiac disease can present with many symptoms, including typical gastrointestinal symptoms (e.g. diarrhea, steatorrhea, weight loss, bloating, flatulence, abdominal pain) and also non-gastrointestinal abnormalities (e.g. abnormal liver function tests, iron deficiency anemia, bone disease, skin disorders, and many other protean manifestations). Indeed, many individuals with celiac disease may have no symptoms at all. Celiac disease is usually detected by serologic testing of celiac-specific antibodies. The diagnosis is confirmed by duodenal mucosal biopsies. Both serology and biopsy should be performed on a gluten-containing diet. The treatment for celiac disease is primarily a gluten-free diet (GFD), which requires significant patient education, motivation, and follow-up. Non-responsive celiac disease occurs frequently, particularly in those diagnosed in adulthood. Persistent or recurring symptoms should lead to a review of the patient’s original diagnosis to exclude alternative diagnoses, a review of the GFD to ensure there is no obvious gluten contamination, and serologic testing to confirm adherence with the GFD. In addition, evaluation for disorders associated with celiac disease that could cause persistent symptoms, such as microscopic colitis, pancreatic exocrine dysfunction, and complications of celiac disease, such as enteropathy-associated lymphoma or refractory celiac disease, should be entertained. Newer therapeutic modalities are being studied in clinical

Unravelling the Complexity of Inherited Retinal Dystrophies Molecular Testing: Added Value of Targeted Next-Generation Sequencing

Directory of Open Access Journals (Sweden)

Isabella Bernardis

2016-01-01

Full Text Available To assess the clinical utility of targeted Next-Generation Sequencing (NGS for the diagnosis of Inherited Retinal Dystrophies (IRDs, a total of 109 subjects were enrolled in the study, including 88 IRD affected probands and 21 healthy relatives. Clinical diagnoses included Retinitis Pigmentosa (RP, Leber Congenital Amaurosis (LCA, Stargardt Disease (STGD, Best Macular Dystrophy (BMD, Usher Syndrome (USH, and other IRDs with undefined clinical diagnosis. Participants underwent a complete ophthalmologic examination followed by genetic counseling. A custom AmpliSeq™ panel of 72 IRD-related genes was designed for the analysis and tested using Ion semiconductor Next-Generation Sequencing (NGS. Potential disease-causing mutations were identified in 59.1% of probands, comprising mutations in 16 genes. The highest diagnostic yields were achieved for BMD, LCA, USH, and STGD patients, whereas RP confirmed its high genetic heterogeneity. Causative mutations were identified in 17.6% of probands with undefined diagnosis. Revision of the initial diagnosis was performed for 9.6% of genetically diagnosed patients. This study demonstrates that NGS represents a comprehensive cost-effective approach for IRDs molecular diagnosis. The identification of the genetic alterations underlying the phenotype enabled the clinicians to achieve a more accurate diagnosis. The results emphasize the importance of molecular diagnosis coupled with clinic information to unravel the extensive phenotypic heterogeneity of these diseases.

Congenital heart disease: a hard case for differential diagnosis and treatment

Directory of Open Access Journals (Sweden)

David Gonçalves Nordon

2012-04-01

Full Text Available ABSTRACT Congenital heart diseases are important malformations that might compromise not only the patient's survival, but also his/her quality of life. We present the case of a female newborn who presented cardiovascular unbalance and cianosis in spite of her previous month of life without any complication. Her differential diagnosis was rather difficult, due not only to restrictions of exams available for diagnosis, but also to their sensibility and specificity. We discuss such differential diagnosis and the complicated development of the case.

Enteroscopy in the diagnosis and management of celiac disease.

Science.gov (United States)

Rondonotti, Emanuele; Villa, Federica; Saladino, Valeria; de Franchis, Roberto

2009-07-01

Esophagogastroduodenoscopy (EGD) with 3 to 6 biopsies in the descending duodenum is the gold standard for the diagnosis of celiac disease. At the time of the first diagnosis of celiac disease, an extensive evaluation of the small bowel is not recommended. However, video capsule endoscopy, because of its good sensitivity and specificity in recognizing the Endoscopic features of celiac disease, can be considered a valid alternative to EGD in patients unable or unwilling to undergo EGD with biopsies. Capsule endoscopy is also a possible option in selected cases with strong suspicion of celiac disease but negative first-line tests. In evaluating patients with refractory or complicated celiac disease, in whom a complete evaluation of the small bowel is mandatory (at least in refractory celiac disease type II patients) because of the possible presence of complications beyond the reach of conventional endoscopes, both capsule endoscopy and balloon-assisted enteroscopy have been found to be helpful. In these patients, capsule endoscopy offers several advantages: it is well tolerated, it allows inspection of the entire small bowel, and it is able to recognize subtle mucosal changes. However, in this setting, capsule endoscopy should ideally be coupled with imaging techniques that provide important information about the thickness of the wall of the intestine and about extraluminal abnormalities. Although deep enteroscopy (such as balloon enteroscopy) is expensive, time-consuming, and potentially risky in these frail patients, they may have a key role, because they make it possible to take tissue samples from deep in the small intestine.

Lyme disease and Bell's palsy: an epidemiological study of diagnosis and risk in England.

Science.gov (United States)

Cooper, Lilli; Branagan-Harris, Michael; Tuson, Richard; Nduka, Charles

2017-05-01

Lyme disease is caused by a tick-borne spirochaete of the Borrelia species. It is associated with facial palsy, is increasingly common in England, and may be misdiagnosed as Bell's palsy. To produce an accurate map of Lyme disease diagnosis in England and to identify patients at risk of developing associated facial nerve palsy, to enable prevention, early diagnosis, and effective treatment. Hospital episode statistics (HES) data in England from the Health and Social Care Information Centre were interrogated from April 2011 to March 2015 for International Classification of Diseases 10th revision (ICD-10) codes A69.2 (Lyme disease) and G51.0 (Bell's palsy) in isolation, and as a combination. Patients' age, sex, postcode, month of diagnosis, and socioeconomic groups as defined according to the English Indices of Deprivation (2004) were also collected. Lyme disease hospital diagnosis increased by 42% per year from 2011 to 2015 in England. Higher incidence areas, largely rural, were mapped. A trend towards socioeconomic privilege and the months of July to September was observed. Facial palsy in combination with Lyme disease is also increasing, particularly in younger patients, with a mean age of 41.7 years, compared with 59.6 years for Bell's palsy and 45.9 years for Lyme disease ( P = 0.05, analysis of variance [ANOVA]). Healthcare practitioners should have a high index of suspicion for Lyme disease following travel in the areas shown, particularly in the summer months. The authors suggest that patients presenting with facial palsy should be tested for Lyme disease. © British Journal of General Practice 2017.

Improved Diagnosis and Care for Rare Diseases through Implementation of Precision Public Health Framework.

Science.gov (United States)

Baynam, Gareth; Bowman, Faye; Lister, Karla; Walker, Caroline E; Pachter, Nicholas; Goldblatt, Jack; Boycott, Kym M; Gahl, William A; Kosaki, Kenjiro; Adachi, Takeya; Ishii, Ken; Mahede, Trinity; McKenzie, Fiona; Townshend, Sharron; Slee, Jennie; Kiraly-Borri, Cathy; Vasudevan, Anand; Hawkins, Anne; Broley, Stephanie; Schofield, Lyn; Verhoef, Hedwig; Groza, Tudor; Zankl, Andreas; Robinson, Peter N; Haendel, Melissa; Brudno, Michael; Mattick, John S; Dinger, Marcel E; Roscioli, Tony; Cowley, Mark J; Olry, Annie; Hanauer, Marc; Alkuraya, Fowzan S; Taruscio, Domenica; Posada de la Paz, Manuel; Lochmüller, Hanns; Bushby, Kate; Thompson, Rachel; Hedley, Victoria; Lasko, Paul; Mina, Kym; Beilby, John; Tifft, Cynthia; Davis, Mark; Laing, Nigel G; Julkowska, Daria; Le Cam, Yann; Terry, Sharon F; Kaufmann, Petra; Eerola, Iiro; Norstedt, Irene; Rath, Ana; Suematsu, Makoto; Groft, Stephen C; Austin, Christopher P; Draghia-Akli, Ruxandra; Weeramanthri, Tarun S; Molster, Caron; Dawkins, Hugh J S

2017-01-01

Public health relies on technologies to produce and analyse data, as well as effectively develop and implement policies and practices. An example is the public health practice of epidemiology, which relies on computational technology to monitor the health status of populations, identify disadvantaged or at risk population groups and thereby inform health policy and priority setting. Critical to achieving health improvements for the underserved population of people living with rare diseases is early diagnosis and best care. In the rare diseases field, the vast majority of diseases are caused by destructive but previously difficult to identify protein-coding gene mutations. The reduction in cost of genetic testing and advances in the clinical use of genome sequencing, data science and imaging are converging to provide more precise understandings of the 'person-time-place' triad. That is: who is affected (people); when the disease is occurring (time); and where the disease is occurring (place). Consequently we are witnessing a paradigm shift in public health policy and practice towards 'precision public health'.Patient and stakeholder engagement has informed the need for a national public health policy framework for rare diseases. The engagement approach in different countries has produced highly comparable outcomes and objectives. Knowledge and experience sharing across the international rare diseases networks and partnerships has informed the development of the Western Australian Rare Diseases Strategic Framework 2015-2018 (RD Framework) and Australian government health briefings on the need for a National plan.The RD Framework is guiding the translation of genomic and other technologies into the Western Australian health system, leading to greater precision in diagnostic pathways and care, and is an example of how a precision public health framework can improve health outcomes for the rare diseases population.Five vignettes are used to illustrate how policy

HIV-associated salivary gland disease--clinical or imaging diagnosis?

Science.gov (United States)

da Silva Rath, Inês Beatriz; Beltrame, Ana Paula C A; Carvalho, Aroldo P; Schaeffer, Marcela B; Almeida, Izabel C S

2015-07-01

This work aimed at studying the salivary gland disease (SGD) as it relates to associated factors, such as persistent generalised lymphadenopathy (PGL), lymphocytic interstitial pneumonia (LIP), clinical and immunological features of AIDS, and salivary flow rate and pH, as well as at exploring the relationship between the clinical diagnosis and the imaging diagnosis by ultrasound (US) examination of the parotid glands. Information regarding the observation of parotid gland enlargement, PGL, LIP, and clinical and immunological features of AIDS was gathered from medical records, and a saliva sample for unstimulated salivary flow rate and pH measurement was collected from 142 children aged 3 through 10 years treated at the Department of Infectious Diseases of Joana de Gusmão Children's Hospital, Florianópolis, SC, Brazil. High-resolution ultrasonography was performed in 58 children. Pearson's chi-square test and t-test were used to evaluate the association between the variables. A significant association was found between SGD and LIP. Ultrasound revealed a 50% higher incidence of SGD that was not reported in the patients' records. US examination proved to be essential for the correct diagnosis and monitoring of the progression of HIV/SGD. © 2014 BSPD, IAPD and John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Variations in cardiovascular disease under-diagnosis in England: national cross-sectional spatial analysis

Directory of Open Access Journals (Sweden)

Walford Hannah

2011-03-01

Full Text Available Abstract Background There is under-diagnosis of cardiovascular disease (CVD in the English population, despite financial incentives to encourage general practices to register new cases. We compared the modelled (expected and diagnosed (observed prevalence of three cardiovascular conditions- coronary heart disease (CHD, hypertension and stroke- at local level, their geographical variation, and population and healthcare predictors which might influence diagnosis. Methods Cross-sectional observational study in all English local authorities (351 and general practices (8,372 comparing model-based expected prevalence with diagnosed prevalence on practice disease registers. Spatial analyses were used to identify geographic clusters and variation in regression relationships. Results A total of 9,682,176 patients were on practice CHD, stroke and transient ischaemic attack, and hypertension registers. There was wide spatial variation in observed: expected prevalence ratios for all three diseases, with less than five per cent of expected cases diagnosed in some areas. London and the surrounding area showed statistically significant discrepancies in observed: expected prevalence ratios, with observed prevalence much lower than the epidemiological models predicted. The addition of general practitioner supply as a variable yielded stronger regression results for all three conditions. Conclusions Despite almost universal access to free primary healthcare, there may be significant and highly variable under-diagnosis of CVD across England, which can be partially explained by persistent inequity in GP supply. Disease management studies should consider the possible impact of under-diagnosis on population health outcomes. Compared to classical regression modelling, spatial analytic techniques can provide additional information on risk factors for under-diagnosis, and can suggest where healthcare resources may be most needed.

Gestational Trophoblastic Disease: A Multimodality Imaging Approach with Impact on Diagnosis and Management

International Nuclear Information System (INIS)

Dhanda, S.; Ramani, S.; Dhanda, S.; Ramani, S.; Thakur, M.

2014-01-01

Gestational trophoblastic disease is a condition of uncertain etiology, comprised of hydatiform mole (complete and partial), invasive mole, choriocarcinoma, and placental site trophoblastic tumor. It arises from abnormal proliferation of trophoblastic tissue. Early diagnosis of gestational trophoblastic disease and its potential complications is important for timely and successful management of the condition with preservation of fertility. Initial diagnosis is based on a multimodality approach: encompassing clinical features, serial quantitative β-hCG titers, and pelvic ultrasonography. Pelvic magnetic resonance imaging (MRI) is sometimes used as a problem-solving tool to assess the depth of myometrial invasion and extra uterine disease spread in equivocal and complicated cases. Chest radiography, body computed tomography (CT), and brain MRI have been recommended as investigative tools for overall disease staging. Angiography has a role in management of disease complications and metastases. Efficacy of PET (positron emission tomography) and PET/CT in the evaluation of recurrent or metastatic disease has not been adequately investigated yet. This paper discusses the imaging features of gestational trophoblastic disease on various imaging modalities and the role of different imaging techniques in the diagnosis and management of this entity. 1. Introduction Gestational trophoblastic disease (GTD) refers to an abnormal trophoblastic proliferation composed of a broad spectrum of lesions ranging from benign, albeit pre malignant hydatiform mole (complete and partial), through to the aggressive invasive mole, choriocarcinoma

Preventing gatekeeping delays in the diagnosis of rare diseases

NARCIS (Netherlands)

de Vries, E.; Fransen, L.; van den Aker, M.; Meijboom, B.R.

2018-01-01

GPs acting as gatekeepers render a healthcare system easily accessible as well as affordable. However, gatekeeping can have an important drawback: it may hamper timely diagnosis and treatment of patients suffering from a rare disease (incidence <1:2000),1 especially if patients present with common

PCR/LDR/universal array platforms for the diagnosis of infectious disease.

Science.gov (United States)

Pingle, Maneesh; Rundell, Mark; Das, Sanchita; Golightly, Linnie M; Barany, Francis

2010-01-01

Infectious diseases account for between 14 and 17 million deaths worldwide each year. Accurate and rapid diagnosis of bacterial, fungal, viral, and parasitic infections is therefore essential to reduce the morbidity and mortality associated with these diseases. Classical microbiological and serological methods have long served as the gold standard for diagnosis but are increasingly being replaced by molecular diagnostic methods that demonstrate increased sensitivity and specificity and provide an identification of the etiologic agent in a shorter period of time. PCR/LDR coupled with universal array detection provides a highly sensitive and specific platform for the detection and identification of bacterial and viral infections.

Pain in Fabry Disease: Practical Recommendations for Diagnosis and Treatment.

Science.gov (United States)

Politei, Juan M; Bouhassira, Didier; Germain, Dominique P; Goizet, Cyril; Guerrero-Sola, Antonio; Hilz, Max J; Hutton, Elspeth J; Karaa, Amel; Liguori, Rocco; Üçeyler, Nurcan; Zeltzer, Lonnie K; Burlina, Alessandro

2016-07-01

Patients with Fabry disease (FD) characteristically develop peripheral neuropathy at an early age, with pain being a crucial symptom of underlying pathology. However, the diagnosis of pain is challenging due to the heterogeneous and nonspecific symptoms. Practical guidance on the diagnosis and management of pain in FD is needed. In 2014, experts met to discuss recent advances on this topic and update clinical guidance. Emerging disease-specific tools, including FabryScan, Fabry-specific Pediatric Health and Pain Questionnaire, and Würzburg Fabry Pain Questionnaire, and more general tools like the Total Symptom Score can aid diagnosis, characterization, and monitoring of pain in patients with FD. These tools can be complemented by more objective and quantifiable sensory testing. In male and female patients of any age, pain related to FD can be an early indication to start disease-specific enzyme replacement therapy before potentially irreversible organ damage to the kidneys, heart, or brain occurs. To improve treatment outcomes, pain should be diagnosed early in unrecognized or newly identified FD patients. Treatment should include: (a) enzyme replacement therapy controlling the progression of underlying pathology; (b) adjunctive, symptomatic pain management with analgesics for chronic neuropathic and acute nociceptive, and inflammatory or mixed pain; and (c) lifestyle modifications. © 2016 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.

Hirschsprung's disease diagnosis: Comparison of immunohistochemical, hematoxilin and eosin staining

OpenAIRE

Memarzadeh, Mehrdad; Talebi, Ardeshir; Edalaty, Masod; Hosseinpour, Mehrdad; Vahidi, Nasrin

2009-01-01

Background: The diagnosis of Hirschsprung's disease (HD) is based on the absence of ganglion cells. In hemotoxilin and eosin (H and E) as well as acetylcholine esterase staining there are limitations in the diagnosis of immature ganglion cells in neonates. Methods: In this prospective study, 54 biopsies taken from suspected HD patients (five mucosal specimens and 49 full thickness specimens) were studied. In the laboratory, after preparing sections of paraffin embedded tissues, H and E staini...

Recent tendency in diagnosis of thyroid diseases

International Nuclear Information System (INIS)

Koizumi, Kiyoshi; Ito, Hiroshi; Tatsuno, Ikuro

1979-01-01

Various new approaches have been recently investigated in diagnosis of thyroid diseases with the progress of nuclear medicine. sup(99m)TcO 4 - has become a routinely used radiopharmaceutical in thyroid scan. sup(99m)TcO 4 - thyroid uptake was evaluated by using thyroid-t-high ratio. 123 I thyroid scan is more valuable than 131 I scan because of its short half time and low radiation exposure. We use 123 I particulary in functional analysis of thyroid hot nodule. 201 Tl scans were performed in patients with cold nodule. All thyroid cancer patients showed 201 Tl positive accumulation in thyroid nodule. However, even in benign diseases 201 Tl was accumulated. 201 Tl scan will be most effectively used in detecting the metastatic lesions from thyroid cancer. Serum rT 3 concentration in various diseases was evaluated by RIA method. Serum TBG concentration in various diseases was evaluated by RIA method and T 4 /TBG ratio was evaluated. Serum anti-thyroglobulin antibody titer in thyroid diseases was evaluated by RIA method. It was more objective than widely used tanned red cell hemagglutinin method. (author)

A possible new diagnostic biomarker in early diagnosis of Alzheimer's disease

DEFF Research Database (Denmark)

Kork, Felix; Holthues, Jan; Hellweg, Rainer

2009-01-01

Early diagnosis in patients with Alzheimer's disease (AD) is of great importance since only a sufficient treatment in early stages of this disease helps to keep patients in an autonomous state for as long as possible. Until now, there is no single diagnostic biomarker for AD derived from material...

Diagnosis and management of acute exacerbation of chronic obstructive pulmonary disease [digest].

Science.gov (United States)

Holden, Van; Slack, Donald; McCurdy, Michael T; Shah, Nirav G; Gupta, Nachi; Nusbaum, Jeffrey

2017-10-20

Acute exacerbation of chronic obstructive pulmonary disease (COPD) is a clinical diagnosis that is based on changes in dyspnea, cough, and/or sputum production in a COPD patient; however, patients presenting with an acute exacerbation may be undiagnosed or have a variety of comorbid conditions that can complicate diagnosis. This issue presents strategies and algorithms for the early use of evidence-based interventions, including appropriate use of antibiotics, bronchodilators, and corticosteroids, along with noninvasive ventilation with capnography, to minimize morbidity and mortality associated with this disease. [Points & Pearls is a digest of Emergency Medicine Practice.].

Serum transglutaminase 3 antibodies correlate with age at celiac disease diagnosis.

Science.gov (United States)

Salmi, Teea T; Kurppa, Kalle; Hervonen, Kaisa; Laurila, Kaija; Collin, Pekka; Huhtala, Heini; Saavalainen, Päivi; Sievänen, Harri; Reunala, Timo; Kaukinen, Katri

2016-06-01

Transglutaminase (TG)2 is the autoantigen in celiac disease, but also TG3 antibodies have been detected in the serum of celiac disease patients. To investigate the correlations between serum TG3 antibodies and clinical and histological manifestations of celiac disease and to assess gluten-dependency of TG3 antibodies. Correlations between serum TG3 antibody levels measured from 119 adults and children with untreated coeliac disease and the demographic data, clinical symptoms, celiac antibodies, histological data and results of laboratory tests and bone mineral densities were tested. TG3 antibodies were reinvestigated in 97 celiac disease patients after 12 months on a gluten-free diet (GFD). TG3 antibody titers were shown to correlate with the age at celiac disease diagnosis. Further, negative correlation with TG3 antibodies and intestinal γδ+ cells at diagnosis and on GFD was detected. Correlations were not detected with the clinical manifestation of celiac disease, TG2 or endomysial autoantibodies, laboratory values, severity of mucosal villous atrophy, associated diseases or complications. TG3 antibody titers decreased on GFD in 56% of the TG3 antibody positive patients. Serum TG3 antibody positivity in celiac disease increases as the diagnostic age rises. TG3 antibodies did not show similar gluten-dependency as TG2 antibodies. Copyright © 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Tiny But Mighty: Promising Roles of MicroRNAs in the Diagnosis and Treatment of Parkinson's Disease

Institute of Scientific and Technical Information of China (English)

Ying Wang; Zhaofei Yang; Weidong Le

2017-01-01

Parkinson's disease (PD) is the second most common age-related neurodegenerative disorder after Alzheimer's disease.To date,the clinical diagnosis of PD is primarily based on the late onset of motor impairments.Unfortunately,at this stage,most of the dopaminergic neurons may have already been lost,leading to the limited clinical benefits of current therapeutics.Therefore,early identification of PD,especially at the prodromal stage,is still a main challenge in the diagnosis and management of this disease.Recently,microRNAs (miRNAs) in cerebrospinal fluid or peripheral blood have been proposed as putative biomarkers to assist in PD diagnosis and therapy.In this review,we systematically summarize the changes of miRNA expression profiles in PD patients,and highlight their putative roles in the diagnosis and treatment of this devastating disease.

Effect of delayed diagnosis on disease course and management of Churg-Strauss syndrome: a retrospective study.

Science.gov (United States)

Sokołowska, Barbara; Szczeklik, Wojciech; Mastalerz, Lucyna; Kuczia, Paweł; Wodkowski, Michał; Stodółkiewicz, Edyta; Macioł, Karolina; Musiał, Jacek

2013-03-01

Delayed diagnosis in patients with Churg-Strauss syndrome (CSS) is largely attributed to the variable and nonspecific presentation of the disease's initial symptoms. The aim of the study was to evaluate the effect of delayed diagnosis on the course of CSS. We conducted a retrospective study of 30 CSS patients followed up in our department. In each patient, we assessed the delay in CSS diagnosis (the time when patients already fulfilled four out of six of the American College of Rheumatology criteria and the diagnosis was not yet established), the disease activity at the time of diagnosis, and organ involvement during CSS course. A median value of 2 weeks was chosen as the cutoff point after which the diagnosis was considered as delayed. Sixteen patients were diagnosed before (group 1) and 14 patients after this cutoff point (group 2). In group 2, we found a higher Birmingham Vasculitis Activity Score at the moment of diagnosis (20.4 vs 25.1, p < 0.05) and a more severe disease course, resulting in more frequent hospitalization rates (0.64 vs 2.26/year, p < 0.00001), higher corticosteroids dose requirements (5.87 vs 11.57 mg/day converted to methylprednisolone, p < 0.0001), and additional immunosuppressive therapy administration (56.2 vs 92.8 %, p < 0.05) to maintain disease remission. All six perinuclear pattern of antineutrophil cytoplasmic antibobodies (pANCA)-positive patients (20 %) were found in group 1. Concluding, the delay in diagnosis of CSS of more than 2 weeks was found to be associated with a disease course that was more severe. The presence of the pANCA antibodies may occasionally facilitate establishment of the diagnosis.

Exercise thallium-201 scintigraphy in the diagnosis and prognosis of coronary artery disease

International Nuclear Information System (INIS)

Kotler, T.S.; Diamond, G.A.

1990-01-01

The objective of this study is to determine the discriminant accuracy of exercise thallium-201 myocardial perfusion scintigraphy for the diagnosis and prognosis of patients with known or suspected coronary artery disease. This is a survey of the National Library of Medicine MEDLINE database. The key medical subject headings used were coronary disease, myocardial infarction, radionuclide imaging, and thallium. A total of 122 retrieved studies were considered relevant and were reviewed in depth. Only studies reporting both the sensitivity and specificity of thallium scintigraphy were analyzed. Discriminant accuracy for diagnosis and prognosis was summarized in terms of pooled sensitivity and specificity. Exercise thallium scintigraphy is useful in the noninvasive diagnosis of coronary artery disease, especially in patients with abnormal resting electrocardiograms, restricted exercise tolerance, and intermediate probability of having disease at the time of testing as well as of defining the prognosis of patients with known or suspected coronary artery disease, especially in those with previous myocardial infarction. Because of various shortcomings in the published record, however, the marginal discriminant accuracy and cost effectiveness of thallium scintigraphy compared with conventional clinical assessment and exercise electrocardiography remain controversial. 193 references

Wilson's Disease: a challenge of diagnosis. The 5-year experience of a tertiary centre.

Science.gov (United States)

Gheorghe, Liana; Popescu, Irinel; Iacob, Speranta; Gheorghe, Cristian; Vaidan, Roxana; Constantinescu, Alexandra; Iacob, Razvan; Becheanu, Gabriel; Angelescu, Corina; Diculescu, Mircea

2004-09-01

Because molecular diagnosis is considered impractical and no patognomonic features have been described, diagnosis of Wilson's disease (WD) using clinical and biochemical findings is still challenging. We analysed predictive factors for the diagnosis in 55 patients with WD diagnosed in our centre between 1st January 1999 and 1st April 2004. All patients presented predominant liver disease classified as: 1) asymptomatic, found incidentally, 2) chronic hepatitis or cirrhosis, or 3) fulminant hepatic failure. Diagnosis was considered as classic (two out of the three following criteria: 1) serum ceruloplasmin 250 mg/g dry weight liver tissue), and non-classic (clinical manifestations plus laboratory parameters suggesting impaired copper metabolism). The association between the predictive factors and non-classic diagnosis was assessed based on the level of statistical significance (p value18 years (p=0.03), increased copper excretion (p<0.0001), Coombs-negative hemolysis (p=0.03), absence of neurological manifestations (p<0.0001). Multivariate analysis identified age over 18 years, increased urinary copper, and isolated hepatic involvement as independent predictors. In clinical practice, WD should be considered also in patients who do not fulfil classic criteria. Independent factors associated with non-classic diagnosis were age over 18 years, increased cupruresis and isolated liver disease.

BLAT2DOLite: An Online System for Identifying Significant Relationships between Genetic Sequences and Diseases.

Directory of Open Access Journals (Sweden)

Liang Cheng

Full Text Available The significantly related diseases of sequences could play an important role in understanding the functions of these sequences. In this paper, we introduced BLAT2DOLite, an online system for annotating human genes and diseases and identifying the significant relationships between sequences and diseases. Currently, BLAT2DOLite integrates Entrez Gene database and Disease Ontology Lite (DOLite, which contain loci of gene and relationships between genes and diseases. It utilizes hypergeometric test to calculate P-values between genes and diseases of DOLite. The system can be accessed from: http://123.59.132.21:8080/BLAT2DOLite. The corresponding web service is described in: http://123.59.132.21:8080/BLAT2DOLite/BLAT2DOLiteIDMappingPort?wsdl.

Addressing challenges in the diagnosis and treatment of rare genetic diseases.

Science.gov (United States)

Boycott, Kym M; Ardigó, Diego

2018-03-01

The past 5 years have seen an unprecedented rate of discovery of genes that cause rare diseases and with it a commensurate increase in the number of diagnosable but nevertheless untreatable disorders. Here, we discuss the increasing opportunity for diagnosis and therapy of rare diseases and how to tackle the associated challenges.

Advances in diagnosis and management of celiac disease.

Science.gov (United States)

Kelly, Ciarán P; Bai, Julio C; Liu, Edwin; Leffler, Daniel A

2015-05-01

Celiac disease is an autoimmune disorder that is induced by dietary gluten in genetically predisposed individuals. It has a prevalence of approximately 1% in many populations worldwide. New diagnoses have increased substantially, owing to increased awareness, better diagnostic tools, and probable real increases in incidence. The breadth of recognized clinical presentations continues to expand, making the disorder highly relevant to all physicians. Newer diagnostic tools, including serologic tests for antibodies against tissue transglutaminase and deamidated gliadin peptide, greatly facilitate diagnosis. Tests for celiac-permissive HLA-DQ2 and HLA-DQ8 molecules are useful in defined clinical situations. Celiac disease is diagnosed by histopathologic examination of duodenal biopsy specimens. However, according to recent controversial guidelines, a diagnosis can be made without a biopsy in certain circumstances, especially in children. Symptoms, mortality, and risk for malignancy each can be reduced by adherence to a gluten-free diet. This treatment is a challenge, however, because the diet is expensive, socially isolating, and not always effective in controlling symptoms or intestinal damage. Hence, there is increasing interest in developing nondietary therapies. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

AUDIOME: a tiered exome sequencing-based comprehensive gene panel for the diagnosis of heterogeneous nonsyndromic sensorineural hearing loss.

Science.gov (United States)

Guan, Qiaoning; Balciuniene, Jorune; Cao, Kajia; Fan, Zhiqian; Biswas, Sawona; Wilkens, Alisha; Gallo, Daniel J; Bedoukian, Emma; Tarpinian, Jennifer; Jayaraman, Pushkala; Sarmady, Mahdi; Dulik, Matthew; Santani, Avni; Spinner, Nancy; Abou Tayoun, Ahmad N; Krantz, Ian D; Conlin, Laura K; Luo, Minjie

2018-03-29

PurposeHereditary hearing loss is highly heterogeneous. To keep up with rapidly emerging disease-causing genes, we developed the AUDIOME test for nonsyndromic hearing loss (NSHL) using an exome sequencing (ES) platform and targeted analysis for the curated genes.MethodsA tiered strategy was implemented for this test. Tier 1 includes combined Sanger and targeted deletion analyses of the two most common NSHL genes and two mitochondrial genes. Nondiagnostic tier 1 cases are subjected to ES and array followed by targeted analysis of the remaining AUDIOME genes.ResultsES resulted in good coverage of the selected genes with 98.24% of targeted bases at >15 ×. A fill-in strategy was developed for the poorly covered regions, which generally fell within GC-rich or highly homologous regions. Prospective testing of 33 patients with NSHL revealed a diagnosis in 11 (33%) and a possible diagnosis in 8 cases (24.2%). Among those, 10 individuals had variants in tier 1 genes. The ES data in the remaining nondiagnostic cases are readily available for further analysis.ConclusionThe tiered and ES-based test provides an efficient and cost-effective diagnostic strategy for NSHL, with the potential to reflex to full exome to identify causal changes outside of the AUDIOME test.Genetics in Medicine advance online publication, 29 March 2018; doi:10.1038/gim.2018.48.

Computer-Aided Characterization and Diagnosis of Diffuse Liver Diseases Based on Ultrasound Imaging: A Review.

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Bharti, Puja; Mittal, Deepti; Ananthasivan, Rupa

2016-04-19

Diffuse liver diseases, such as hepatitis, fatty liver, and cirrhosis, are becoming a leading cause of fatality and disability all over the world. Early detection and diagnosis of these diseases is extremely important to save lives and improve effectiveness of treatment. Ultrasound imaging, a noninvasive diagnostic technique, is the most commonly used modality for examining liver abnormalities. However, the accuracy of ultrasound-based diagnosis depends highly on expertise of radiologists. Computer-aided diagnosis systems based on ultrasound imaging assist in fast diagnosis, provide a reliable "second opinion" for experts, and act as an effective tool to measure response of treatment on patients undergoing clinical trials. In this review, we first describe appearance of liver abnormalities in ultrasound images and state the practical issues encountered in characterization of diffuse liver diseases that can be addressed by software algorithms. We then discuss computer-aided diagnosis in general with features and classifiers relevant to diffuse liver diseases. In later sections of this paper, we review the published studies and describe the key findings of those studies. A concise tabular summary comparing image database, features extraction, feature selection, and classification algorithms presented in the published studies is also exhibited. Finally, we conclude with a summary of key findings and directions for further improvements in the areas of accuracy and objectiveness of computer-aided diagnosis. © The Author(s) 2016.

Optimizing Parkinson's disease diagnosis: the role of a dual nuclear imaging algorithm.

Science.gov (United States)

Langston, J William; Wiley, Jesse C; Tagliati, Michele

2018-01-01

The diagnosis of Parkinson's disease (PD) currently relies almost exclusively on the clinical judgment of an experienced neurologist, ideally a specialist in movement disorders. However, such clinical diagnosis is often incorrect in a large percentage of patients, particularly in the early stages of the disease. A commercially available, objective and quantitative marker of nigrostriatal neurodegeneration was recently provided by 123-iodine 123 I-ioflupane SPECT imaging, which is however unable to differentiate PD from a variety of other parkinsonian syndromes associated with striatal dopamine deficiency. There is evidence to support an algorithm utilizing a dual neuroimaging strategy combining 123 I-ioflupane SPECT and the noradrenergic receptor ligand 123 I-metaiodobenzylguanidine (MIBG), which assesses the post-ganglion peripheral autonomic nervous system. Evolving concepts regarding the synucleinopathy affecting the central and peripheral autonomic nervous systems as part of a multisystem disease are reviewed to sustain such strategy. Data are presented to show how MIBG deficits are a common feature of multisystem Lewy body disease and can be used as a unique feature to distinguish PD from atypical parkinsonisms. We propose that the combination of cardiac (MIBG) and cerebral 123 I-ioflupane SPECT could satisfy one of the most significant unmet needs of current PD diagnosis and management, namely the early and accurate diagnosis of patients with typical Lewy body PD. Exemplary case scenarios will be described, highlighting how dual neuroimaging strategy can maximize diagnostic accuracy for patient care, clinical trials, pre-symptomatic PD screening, and special cases provided by specific genetic mutations associated with PD.

Diagnosis of Charcot-Marie-Tooth Disease

Directory of Open Access Journals (Sweden)

Isabel Banchs

2009-01-01

Full Text Available Charcot-Marie-Tooth (CMT disease or hereditary motor and sensory neuropathy (HMSN is a genetically heterogeneous group of conditions that affect the peripheral nervous system. The disease is characterized by degeneration or abnormal development of peripheral nerves and exhibits a range of patterns of genetic transmission. In the majority of cases, CMT first appears in infancy, and its manifestations include clumsiness of gait, predominantly distal muscular atrophy of the limbs, and deformity of the feet in the form of foot drop. It can be classified according to the pattern of transmission (autosomal dominant, autosomal recessive, or X linked, according to electrophysiological findings (demyelinating or axonal, or according to the causative mutant gene. The classification of CMT is complex and undergoes constant revision as new genes and mutations are discovered. In this paper, we review the most efficient diagnostic algorithms for the molecular diagnosis of CMT, which are based on clinical and electrophysiological data.

Educational inequality in cardiovascular disease depends on diagnosis

DEFF Research Database (Denmark)

Christensen, Anne V; Koch, Mette B; Davidsen, Michael

2016-01-01

BACKGROUND: Social inequality is present in the morbidity as well as the mortality of cardiovascular diseases. This paper aims to quantify and compare the level of educational inequality across different cardiovascular diagnoses. DESIGN: Register based study. METHODS: Comparison of the extent...... index of inequality: -29 (-35.1; -21.9) to -1 (-4.8; -3.8)). CONCLUSION: The degree of educational inequality in cardiovascular diseases depends on the diagnosis, with the highest inequality in ischaemic heart disease, acute myocardial infarction, heart failure and stroke. Small differences were found...... of inequality across different cardiovascular diagnoses requires a measure of inequality which is comparable across subgroups with different educational distributions. The slope index of inequality and the relative index of inequality were applied for measuring inequalities in incidence of six cardiovascular...

Exome Sequencing for cerebral palsies: Opening windows for differential diagnosis

Directory of Open Access Journals (Sweden)

D. Suresh Bhargav

2017-10-01

Full Text Available DNA sequencing technologies played a critical role in the last two decades in expanding our understanding of genetic spectrum behind neurodevelopmental disorders. Recently, induction MPS in the area of medical genetics provided chance for differential diagnosis and/or reverse phenotyping of cerebral palsies and many other developmental disorders. Here we present how ES through MPS has identified causative mutations and showed scope for further characterization of the neurodevelopmental disorders. Here we report and discuss four cases (5Y to 12Y who were diagnosed as CP with mild or moderate ID. Whole Exome libraries were constructed using Exome RDY panel and sequenced on Ion Proton. The reads generated were aligned to hg19 and variants were annotated and prioritized using Ion Reporter. In Cases-I & II a homozygous mutation in PMM2 gene (NM_000303.2, c.710C>T, p.THR237ARG and a novel nonsense mutation in gene SLC35A2 (NM_005660.2, c.1024C>T, p.Arg342Ter which are known to cause congenital disorder of glycosylation type Ia (MIM: 212065 and type IIm SOMATIC MOSAIC (MIM: 300896 were identified, respectively. In case-III (two male siblings ES identified a novel Frame Shift (FS mutation in APRATAXIN (APTX gene (NM_001195248.1, c.638delG, p.Arg213fs, rs150886026 which are known to cause ATAXIA-OCULOMOTOR APRAXIA 1; AOA1 (MIM: 208920. Brain imaging in Case-IV is suggestive of Joubert syndrome with hearing loss, we identified a missense mutation in AHI1 gene (NM_001134830.1, c.2023G>A, p.Asp675Asn and also a nonsense mutation in gene GJB2 (NM_004004.5, c.71G>A, p.Trp24Ter which explains the hearing impairment in the case. Mutations in cases and parent(s were confirmed on 3500 Genetic Analyzer revealed Autosomal recessive or X-linked dominant and somatic mosaicism pattern of inheritance. Reverse phenotyping was convincing for Case I & II.  Case III phenotype was delineated by the identification of responsible gene /mutation.  Complex phenotype of Case

FindZebra - using machine learning to aid diagnosis of rare diseases

DEFF Research Database (Denmark)

Svenstrup, Dan Tito

FindZebra is a search engine for rare diseases intended to act as a diagnosis decision support system (DDSS) capable of assisting the user both during and after a search. Rare diseases are diseases that affect only a small part of the population (less than one in two thousand). Currently around...... retrieval systems. Improving retrieval performance is important, but is not the only way of improving the success rate of a DDSS such as FindZebra. Following an unsuccessful search, the search engine should assist the user by indicating what information is likely to be missing. This idea is called...... language and the search engine should then give a suggestion for a differential diagnosis based on all the information contained in a multilingual corpus, not only in the native corpus. Methods for performing multilingual search will be the fourth line of research explored in this dissertation. ...

HM-PAO SPECT in the diagnosis of cerebrovascular disease

International Nuclear Information System (INIS)

Cordes, M.; Rummeny, E.; Reissmann, M.; Fox, K.; Panitz, N.; Pfannenstiel, P.

1987-01-01

Single photon emission computed tomography (SPECT) after injection of 99m-Tc-HM-PAO was used to examine 34 patients whose clinical findings could not exclude a cerebrovascular disease. In all patients an X-ray computed tomography examination was inconclusive for the clinical-neurological findings. The regional cerebral bloodflow was pathologically disturbed in 10 of 34 patients in the HM-PAO SPECT examination. The detection of the regional cerebral bloodflow with HM-PAO SPECT is helpful in the diagnosis of cerebrovascular disease. (orig.) [de

Celiac disease in Saudi children. Evaluation of clinical features and diagnosis

Directory of Open Access Journals (Sweden)

Anjum Saeed

2017-09-01

Full Text Available Objectives: To characterize the clinical presentations and diagnosis including serological tests and histopathological findings in children with celiac disease. Methods: All children (less than 18 years with confirmed celiac disease diagnosed over a 6 year period at a private tertiary care health care center in Riyadh, Saudi Arabia were studied retrospectively. Information collected included demographics, clinical presentation and diagnostic modalities with serology and small intestinal histology reported by Marsh grading. Results: A total of 59 children had confirmed celiac disease. Thirty (50.8% were male. Median age was 8 years (range 1 to 16 years. The mean duration of symptoms before diagnosis was 2.3 (±1.5 years. Classical disease was present only in 30.5%, whereas 69.5% had either non-classical presentations or belonged to high risk groups for celiac disease such as those with type-1 diabetes, autoimmune thyroiditis, Down syndrome and siblings. Failure to thrive was the most common presentation followed by short stature, abdominal pain and chronic diarrhea. Anti-tissue transglutaminase antibody was positive in 91.5%, and titers were no different between those with classical and non-classical disease. All had Marsh-graded biopsy findings consistent with celiac disease. Conclusion: Children with celiac disease usually present with non-classical features. A high index of suspicion needs to be maintained to consider this disorder in the diagnostic workup of pediatric patients. High risk group should be screened early to avoid complications associated with untreated celiac disease.

Differential Diagnosis of Erythmato-Squamous Diseases Using Classification and Regression Tree.

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Maghooli, Keivan; Langarizadeh, Mostafa; Shahmoradi, Leila; Habibi-Koolaee, Mahdi; Jebraeily, Mohamad; Bouraghi, Hamid

2016-10-01

Differential diagnosis of Erythmato-Squamous Diseases (ESD) is a major challenge in the field of dermatology. The ESD diseases are placed into six different classes. Data mining is the process for detection of hidden patterns. In the case of ESD, data mining help us to predict the diseases. Different algorithms were developed for this purpose. we aimed to use the Classification and Regression Tree (CART) to predict differential diagnosis of ESD. we used the Cross Industry Standard Process for Data Mining (CRISP-DM) methodology. For this purpose, the dermatology data set from machine learning repository, UCI was obtained. The Clementine 12.0 software from IBM Company was used for modelling. In order to evaluation of the model we calculate the accuracy, sensitivity and specificity of the model. The proposed model had an accuracy of 94.84% (. 24.42) in order to correct prediction of the ESD disease. Results indicated that using of this classifier could be useful. But, it would be strongly recommended that the combination of machine learning methods could be more useful in terms of prediction of ESD.

Prenatal diagnosis of Werdnig-Hoffmann disease in China

Institute of Scientific and Technical Information of China (English)

无

2003-01-01

Objective To establish a means for prenatal prediction of spinal muscular atrophy (SMA) through survival motor neuron (SMN) gene deletion analysis and genetic counseling in families with a child affected with SMA. Methods Genetic analysis for prenatal prediction of Werdnig-Hoffmann disease was performed in a at risk Chinese family by polymerase chain reaction (PCR)-single-strand conformation polymorphism (SSCP) in SMN gene exons 7 and 8.Results The pregnancy was positive for the homozygous deletion of the SMN gene, thus the fetus was diagnosed as being affected and the pregnancy was terminated.Conclusion This approach is fast and reliable for DNA-based prenatal diagnosis of Werdnig-Hoffmann disease.

Celiac disease diagnosis: impact of guidelines on medical prescription in France.

Science.gov (United States)

Pham, Bach Nga; Musset, Lucile; Chyderiotis, Georges; Olsson, Nils Olivier; Fabien, Nicole

2014-08-01

Celiac disease is a complex autoimmune disease affecting patients of any age, who may present a wide variety of clinical manifestations. Different guidelines for the diagnosis and management of celiac disease have been recently published. The aim of this study was to determine whether the recommendations issued in these guidelines have been adopted by physicians in France when celiac disease was suspected. A total of 5521 physicians were asked to fill in a detailed questionnaire on diagnosing celiac disease to evaluate their medical practice, as to the type of symptoms leading to the suspicion of celiac disease, the prescription of duodenal biopsy or serological tests, the type of serological tests (anti-tissue transglutaminase, anti-endomysium, anti-gliadin and anti-reticulin antibodies, total immunoglobulin A measurement) prescribed to diagnose celiac disease. The analysis of the responses of 256 general practitioners (GPs), 221 gastroenterologists and 227 pediatricians showed that the protean clinical presentations of celiac disease might be better recognized by gastroenterologists and pediatricians than by GPs. Gastroenterologists asked for duodenal biopsy much more often than GPs and pediatricians when celiac disease was suspected. Serological testing and knowledge of critical markers, prescribed to diagnose celiac disease, differed among GPs, gastroenterologists and pediatricians. Analysis of medical prescriptions showed that the recommendations for celiac disease diagnosis are not necessarily followed by physicians, emphasizing the fact that the impact of national or international guidelines on medical behavior should be evaluated. © 2014 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.

Reevaluating Muscle Biopsies in the Diagnosis of Pompe Disease: A Corroborative Report.

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Genge, Angela; Campbell, Natasha

2016-07-01

Previous reports suggest that although a diagnostic muscle biopsy can confirm the presence of Pompe disease, the absence of a definitive biopsy result does not rule out the diagnosis. In this study, we reviewed patients with a limb-girdle syndrome who demonstrated nonspecific abnormalities of muscle, without evidence of the classical changes of acid maltase deficiency. These patients were rescreened for Pompe disease using dried blood spot (DBS) testing. Twenty-seven patients provided blood samples for the DBS test. Four patients underwent subsequent genetic testing. Genetic analysis demonstrated that one patient tested positive for Pompe disease and one patient had one copy of a pathogenic variant. In conclusion, the ability of a diagnostic muscle biopsy to definitively rule out the presence of Pompe disease is limited. There is a role for a screening DBS in all patients presenting with a limb-girdle syndrome without a clear diagnosis.

Application of 18F-FDG PET for the diagnosis and differential diagnosis of Alzheimer's disease and Lewy body dementia

International Nuclear Information System (INIS)

Klisarova, A.; Bochev, P.; Deleva, N.; Dimitrov, I.; Ivanov, B.

2010-01-01

Alzheimer's disease and Lewy body dementia are the two most frequent disorders among degenerative dementias. Their clinical identification and differential diagnosis are often difficult in the early stages when, on the other hand treatment is most effective. FDG-PET assessment of region brain metabolism is a proven method and its application demented patients ensures a higher diagnostic accuracy even at the preclinical stage. It helps resolving cases with difficult differential diagnosis as well. In this paper we discuss the application of the method in Alzheimer's disease and Lev body dementia; we present typical cases of both disorder which were assessed by FDG-PET for the first time in Bulgaria highlighting the methodology and the characteristic imaging findings

An intelligent medical system for diagnosis of bone diseases

International Nuclear Information System (INIS)

Hatzilygeroudis, I.; Vassilakos, P.J.; Tsakalidis, A.

1994-01-01

In this paper, aspects of the design of an intelligent medical system for diagnosis of bone diseases that can be detected by scintigraphic images are presented. The system comprises three major parts: a user interface (UI), a database management system (DBMS), and an expert system (ES). The DBMS is used for manipulation of various patient data. A number of patient cases are selected as prototype and stored in separate database. Diagnosis is performed via the ES, called XBONE, based on patient data. Knowledge is represented via an integrated formalism that combines production rules and a neural network. This results in better representation, and facilitates knowledge acquisition and maintenance. (authors)

[Analysis of qualifications of medical and health institutions and certified doctors for providing occupational disease diagnosis in China].

Science.gov (United States)

Wang, Huan-qiang; Li, Tao; Qi, Fang; Wu, Rui; Nie, Wu; Yu, Chen

2013-10-01

To investigate the qualifications and current situations of the medical and health institutions and certified doctors for providing occupational disease diagnosis in China and to provide a reference for developing relevant policies. Work reports and questionnaires survey were used to investigate the qualifications of all medical and health institutions and certified doctors for providing occupational disease diagnosis in China and their acceptance and diagnosis of occupational disease cases from 2006 to 2010. The rate for the work reports was 100%, and the response rate for the questionnaires was 71.0%. By the end of 2010, in the 31 provincial-level regions (excluding Hong Kong, Macao, and Taiwan) in China, there had been 503 medical and health institutions which were qualified for providing occupational disease diagnosis, including 207 centers for disease control and prevention, accounting for 41.2%, 145 general hospitals, accounting for 28.8%, 69 enterprise-owned hospitals, accounting for 13.7%, and 64 institutes or centers for occupational disease prevention and control, accounting for 12.7%; 4986 certified doctors got the qualification for providing occupational disease diagnosis, with 9.4 certified doctors on average in each institution, and there was 0.65 certified doctor per 100 000 employees. In addition, 16.5% of the institutions got all the qualifications for diagnosing 9 occupational diseases, and 17.1% of the institutions got the qualification for diagnosing one occupational disease. Each certified doctor accepted diagnosis of 16.8 cases of occupational diseases on average every year. A national occupational disease diagnosis network has been established in China, but the imbalance in regional distribution and specialty programs still exists among the qualified medical and health institutions and certified doctors. It is essential to further strengthen the development of regional qualified medical and health institutions and training of qualified

Dry eye disease: pathophysiology, classification, and diagnosis.

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Perry, Henry D

2008-04-01

Dry eye disease (DED) is a multifactorial disorder of the tear film and ocular surface that results in eye discomfort, visual disturbance, and often ocular surface damage. Although recent research has made progress in elucidating DED pathophysiology, currently there are no uniform diagnostic criteria. This article discusses the normal anatomy and physiology of the lacrimal functional unit and the tear film; the pathophysiology of DED; DED etiology, classification, and risk factors; and DED diagnosis, including symptom assessment and the roles of selected diagnostic tests.

Unexpected Diagnosis of Cerebral Toxoplasmosis by 16S and D2 Large-Subunit Ribosomal DNA PCR and Sequencing

DEFF Research Database (Denmark)

Kruse, Alexandra Yasmin Collin; Kvich, Lasse Andersson; Eickhardt-Dalbøge, Steffen Robert

2015-01-01

The protozoan parasite Toxoplasma gondii causes severe opportunistic infections. Here, we report an unexpected diagnosis of cerebral toxoplasmosis. T. gondii was diagnosed by 16S and D2 large-subunit (LSU) ribosomal DNA (rDNA) sequencing of a cerebral biopsy specimen and confirmed by T. gondii...

Computerized tomography in the diagnosis of degenerative vertebral diseases

International Nuclear Information System (INIS)

Bokarev, V.S.; Savchenko, A.P.; Ternovoj, S.K.

1989-01-01

CT and roentgenography were used for the investigation of 78 patients with the radicular syndrome. The state of the intervertebral disks, intervertebral joints and cerebrospinal canal in degenerative vertebral diseases was assessed. CT permits the detection of hernia, protrusion of the intervertebral disks, deformity of the intervertebral joints, and the narrowing of the cerebrospinal canal as a result of degenerative changes, as well as establishing the cause of the affection of neural structures in the cerebrospinal canal, radicular holes. CT possesses some advantages over roentgenography in the diagnosis of degenerative vertebral diseases

[New-generation high-throughput technologies based 'omics' research strategy in human disease].

Science.gov (United States)

Yang, Xu; Jiao, Rui; Yang, Lin; Wu, Li-Ping; Li, Ying-Rui; Wang, Jun

2011-08-01

In recent years, new-generation high-throughput technologies, including next-generation sequencing technology and mass spectrometry method, have been widely applied in solving biological problems, especially in human diseases field. This data driven, large-scale and industrialized research model enables the omnidirectional and multi-level study of human diseases from the perspectives of genomics, transcriptomics and proteomics levels, etc. In this paper, the latest development of the high-throughput technologies that applied in DNA, RNA, epigenomics, metagenomics including proteomics and some applications in translational medicine are reviewed. At genomics level, exome sequencing has been the hot spot of the recent research. However, the predominance of whole genome resequencing in detecting large structural variants within the whole genome level is coming to stand out as the drop of sequencing cost, which also makes it possible for personalized genome based medicine application. At trancriptomics level, e.g., small RNA sequencing can be used to detect known and predict unknown miRNA. Those small RNA could not only be the biomarkers for disease diagnosis and prognosis, but also show the potential of disease treatment. At proteomics level, e.g., target proteomics can be used to detect the possible disease-related protein or peptides, which can be useful index for clinical staging and typing. Furthermore, the application and development of trans-omics study in disease research are briefly introduced. By applying bioinformatics technologies for integrating multi-omics data, the mechanism, diagnosis and therapy of the disease are likely to be systemically explained and realized, so as to provide powerful tools for disease diagnosis and therapies.

Colour atlas on forest disease. Diagnosis of tree diseases. Farbatlas Waldschaeden. Diagnose von Baumkrankheiten

Energy Technology Data Exchange (ETDEWEB)

Hartmann, G.; Winter, K.; Nienhaus, F.; Butin, H.

1988-01-01

The 'Colour Atlas on Forest Disease' facilitates the diagnosis of syndromes due to different causes in 16 genera or species of forest trees. It contains a selection of more than 200 important, frequent, or conspicuous disease phenomena. These include: in a ratio of 8 percent partly novel, complex diseases due to causes not entirely elucidated, 35 percent known forms of damage of abiotic origin (extreme weather conditions, nutrient deficiency, classical damage due to environmental pollution and de-icing salt, damage through herbicides), and 57 percent diseases and harm of biotic origin (fungal infections, infestation with insect pest, bacterial, mycoplasmal, rickettsia-type and viral diseases, other damage). 418 colour photographs show characteristic features of tree diseases and provide clues to causes and possible alternative diseases liable to be mixed up with the actual one. The selection decided on is restricted to symptoms visible externally in the area of the crowns as far as they are distinguishable in the field. (orig./MG) With 418 colour photographs.

Exome Sequencing Fails to Identify the Genetic Cause of Aicardi Syndrome

DEFF Research Database (Denmark)

Lund, Caroline; Striano, Pasquale; Sorte, Hanne Sørmo

2016-01-01

Aicardi syndrome (AS) is a well-characterized neurodevelopmental disorder with an unknown etiology. In this study, we performed whole-exome sequencing in 11 female patients with the diagnosis of AS, in order to identify the disease-causing gene. In particular, we focused on detecting variants in ...

Inversion recovery RARE: Clinical application of T2-weighted CSF-suppressed rapid sequence

International Nuclear Information System (INIS)

Goetz, G.F.; Hennig, J.; Ziyeh, S.

1995-01-01

Inversion-Recovery RARE is a strongly T 2 -weighted fast sequence in which the CSF appears dark. This sequence was used in more than 100 patients. Retrospective analysis of 80 patients with cerebrovascular and inflammatory disease was carried out. The IR-RARE sequence proved to be particularly suitable for identifying small lesions in the neighbourhood of the subarachnoid space. We illustrate the typical contrast provided by this sequence, and describe its characteristics, exemplifying the advantages it offers for the diagnosis of multiple sclerosis, cerebral microangiopathy and brain infarction. (orig.) [de

Computer Aided Medical Diagnosis for the Treatment of Sexually Transmitted Disease (Gonorrhea

Directory of Open Access Journals (Sweden)

Adamu M. Ibrahim

2017-02-01

Full Text Available The World Health Organization (WHO report on the circumstances of clinical facilities in developing countries indicates that, there is considerable efficient delivery of medical services to the rural inhabitants where the services are available, these services are very expensive and not affordable to the average citizen. This has risen inadequacies such as prolonged suffering and even death. The slow process of diagnosis trial and error of diseases can be disastrous when a patient is at the advanced stage of a disease. Here we propose an automated system that can aid the diagnosis of sexually transmitted diseases and suggest adequate drug prescriptions and treatment. To achieve this, an extensive review on related diseases were reevaluated and a common type (gonorrhea was used as an exemplary study. This is based on the Structure Systems Analysis and Design Methodology (SSADM. The paper as shown a system that is most effective and have a fast way of diagnosing and treating sexually transmitted diseases, which serves as a great relief for the doctors and even non-experts in the field.

International Work Group Criteria for the Diagnosis of Alzheimer Disease

NARCIS (Netherlands)

Cummings, J.L.; Dubois, B; Molinuevo, J.L.; Scheltens, P.

2013-01-01

Alzheimer-type biomarker changes are identifiable in asymptomatic and mildly symptomatic predementia phases of Alzheimer disease (AD) and AD dementia. The International Work Group (IWG) guidelines for diagnosis identify a unified spectrum of 3 phases. The classic clinical feature that indicates AD

Celiac disease: Prevalence, diagnosis, pathogenesis and treatment

Science.gov (United States)

Gujral, Naiyana; Freeman, Hugh J; Thomson, Alan BR

2012-01-01

Celiac disease (CD) is one of the most common diseases, resulting from both environmental (gluten) and genetic factors [human leukocyte antigen (HLA) and non-HLA genes]. The prevalence of CD has been estimated to approximate 0.5%-1% in different parts of the world. However, the population with diabetes, autoimmune disorder or relatives of CD individuals have even higher risk for the development of CD, at least in part, because of shared HLA typing. Gliadin gains access to the basal surface of the epithelium, and interact directly with the immune system, via both trans- and para-cellular routes. From a diagnostic perspective, symptoms may be viewed as either “typical” or “atypical”. In both positive serological screening results suggestive of CD, should lead to small bowel biopsy followed by a favourable clinical and serological response to the gluten-free diet (GFD) to confirm the diagnosis. Positive anti-tissue transglutaminase antibody or anti-endomysial antibody during the clinical course helps to confirm the diagnosis of CD because of their over 99% specificities when small bowel villous atrophy is present on biopsy. Currently, the only treatment available for CD individuals is a strict life-long GFD. A greater understanding of the pathogenesis of CD allows alternative future CD treatments to hydrolyse toxic gliadin peptide, prevent toxic gliadin peptide absorption, blockage of selective deamidation of specific glutamine residues by tissue, restore immune tolerance towards gluten, modulation of immune response to dietary gliadin, and restoration of intestinal architecture. PMID:23155333

Targeted exome sequencing and chromosomal microarray for the molecular diagnosis of nevoid basal cell carcinoma syndrome.

Science.gov (United States)

Matsudate, Yoshihiro; Naruto, Takuya; Hayashi, Yumiko; Minami, Mitsuyoshi; Tohyama, Mikiko; Yokota, Kenji; Yamada, Daisuke; Imoto, Issei; Kubo, Yoshiaki

2017-06-01

Nevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant disorder mainly caused by heterozygous mutations of PTCH1. In addition to characteristic clinical features, detection of a mutation in causative genes is reliable for the diagnosis of NBCCS; however, no mutations have been identified in some patients using conventional methods. To improve the method for the molecular diagnosis of NBCCS. We performed targeted exome sequencing (TES) analysis using a multi-gene panel, including PTCH1, PTCH2, SUFU, and other sonic hedgehog signaling pathway-related genes, based on next-generation sequencing (NGS) technology in 8 cases in whom possible causative mutations were not detected by previously performed conventional analysis and 2 recent cases of NBCCS. Subsequent analysis of gross deletion within or around PTCH1 detected by TES was performed using chromosomal microarray (CMA). Through TES analysis, specific single nucleotide variants or small indels of PTCH1 causing inferred amino acid changes were identified in 2 novel cases and 2 undiagnosed cases, whereas gross deletions within or around PTCH1, which are validated by CMA, were found in 3 undiagnosed cases. However, no mutations were detected even by TES in 3 cases. Among 3 cases with gross deletions of PTCH1, deletions containing the entire PTCH1 and additional neighboring genes were detected in 2 cases, one of which exhibited atypical clinical features, such as severe mental retardation, likely associated with genes located within the 4.3Mb deleted region, especially. TES-based simultaneous evaluation of sequences and copy number status in all targeted coding exons by NGS is likely to be more useful for the molecular diagnosis of NBCCS than conventional methods. CMA is recommended as a subsequent analysis for validation and detailed mapping of deleted regions, which may explain the atypical clinical features of NBCCS cases. Copyright © 2017 Japanese Society for Investigative Dermatology. Published by

Next Generation Sequencing As an Aid to Diagnosis and Treatment of an Unusual Pediatric Brain Cancer

Directory of Open Access Journals (Sweden)

John Glod

2014-07-01

Full Text Available Classification of pediatric brain tumors with unusual histologic and clinical features may be a diagnostic challenge to the pathologist. We present a case of a 12-year-old girl with a primary intracranial tumor. The tumor classification was not certain initially, and the site of origin and clinical behavior were unusual. Genomic characterization of the tumor using a Clinical Laboratory Improvement Amendment (CLIA-certified next-generation sequencing assay assisted in the diagnosis and translated into patient benefit, albeit transient. Our case argues that next generation sequencing may play a role in the pathological classification of pediatric brain cancers and guiding targeted therapy, supporting additional studies of genetically targeted therapeutics.

The clinical utility of whole-exome sequencing in the context of rare diseases - the changing tides of medical practice.

Science.gov (United States)

Nguyen, M T; Charlebois, K

2015-10-01

Whole-exome sequencing (WES) carries the potential to facilitate the identification of disease causing genes. This is particularly relevant concerning rare diseases, which proves particularly difficult for physicians to diagnose. However, the complexity of this technology renders its applicability onto the clinical setting uncertain. Our study thus aims to understand physicians' perspectives regarding the clinical utility of WES, particularly for providing a diagnosis for patients with rare diseases. Ten semi-structured interviews were conducted with physicians with experience and familiarity with WES, and the major themes that emerged from our interviews were (i) the relevance of WES in diagnosing patients with rare diseases (appropriateness); (ii) the cost-effectiveness of WES (accessibility), (iii) the practical issues related to the clinical implementation of WES (practicability); and (iv) ethical, legal and social issues (acceptability). Our study highlights how the clinical implementation of WES presents additional challenges where rare diseases are taken into consideration. © 2014 The Authors. Clinical Genetics published by John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Fungal/mycotic diseases of poultry-diagnosis, treatment and control: a review.

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Dhama, Kuldeep; Chakraborty, Sandip; Verma, Amit Kumar; Tiwari, Ruchi; Barathidasan, Rajamani; Kumar, Amit; Singh, Shambhu Dayal

2013-12-01

Fungal/mycotic diseases cause significant economic losses to the poultry industry either due to their direct infectious nature or due to production of mycotoxins, the secondary fungal metabolites produced in grains or poultry feed. Several fungi have created havoc in the poultry industry and some of them cause direct harm to human health due to their zoonotic implications. They are responsible for high morbidity and mortality, especially in young birds and cause stunted growth and diarrhea; and fatal encephalitis. Mycotic dermatitis is a possible health hazard associated with poultry houses. Mycotoxins are the leading cause of producing immunosuppression in birds, which makes them prone to several bacterial and viral infections leading to huge economic losses to the poultry industry. In comparison to bacterial and viral diseases, advances in diagnosis, treatment, prevention and control of fungal diseases in poultry has not taken much attention. Recently, molecular biological tools have been explored for rapid and accurate diagnosis of important fungal infections. Effective prevention and control measures include: appropriate hygiene, sanitation and disinfection, strict biosecurity programme and regular surveillance/monitoring of fungal infections as well as following judicious use of anti-fungal drugs. Precautionary measures during crop production, harvesting and storing and in feed mixing plants can help to check the fungal infections including health hazards of mycotoxins/mycotoxicosis. The present review describes the fungal pathogens causing diseases in poultry/birds, especially focusing to their diagnosis, prevention and control measures, which would help in formulating appropriate strategies to have a check and control on these unwanted troubles to the poultry producers/farmers.

Ultrasonography and computer tomography in the diagnosis of certain abdominal diseases

International Nuclear Information System (INIS)

Wawrzynek, Z.

1981-01-01

Ultrasonography and computer tomography in the diagnosis of digestive tract and spleen diseases as well as traumas are compared. It is concluded that ultrasonography is nearly as usefull as computer tomography. (author)

Celiac disease in Saudi children. Evaluation of clinical features and diagnosis.

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Saeed, Anjum; Assiri, Asaad; Assiri, Hebah; Ullah, Anhar; Rashid, Mohsin

2017-09-01

 Objectives: To characterize the clinical presentations and diagnosis including serological tests and histopathological findings in children with celiac disease. Methods: All children (less than 18 years) with confirmed celiac disease diagnosed over a 6 year period at a private tertiary care health care center in Riyadh,  Saudi Arabia were studied retrospectively. Information collected included demographics, clinical presentation and diagnostic modalities with serology and small intestinal histology reported by Marsh grading. Results: A total of 59 children had confirmed celiac disease. Thirty (50.8%) were male. Median age was 8 years (range 1 to 16 years). The mean duration of symptoms before diagnosis was 2.3 (±1.5) years. Classical disease was present only in 30.5%, whereas 69.5% had either non-classical presentations or belonged to high risk groups for celiac disease such as those with type-1 diabetes, autoimmune thyroiditis, Down syndrome and siblings. Failure to thrive was the most common presentation followed by short stature, abdominal pain and chronic diarrhea. Anti-tissue transglutaminase antibody was positive in 91.5%, and titers were no different between those with classical and non-classical disease. All had Marsh-graded biopsy findings consistent with celiac disease. Conclusion: Children with celiac disease usually present with non-classical features. A high index of suspicion needs to be maintained to consider this disorder in the diagnostic workup of pediatric patients. High risk group should be screened early to avoid complications associated with untreated celiac disease.

Comparison of complement fixation and ELISA for diagnosis of foot-and-mouth disease

International Nuclear Information System (INIS)

Caballero, P.H.; Gonzalez, S.; Orue, P.M.; Vergara, N.N.

1998-01-01

Foot-and-mouth disease (FMD) virus is characterised by its rapid transmission and its great antigenic variability which require a requires a rapid and accurate diagnosis in the laboratory, in order to initiate an immediate response for control. From these studies it is clear that Enzyme linked immunosorbent assay (ELISA) has the advantage over the Complement fixation test (CFT) of being a test of high sensitivity and specificity. Therefore, this technique is now used in our laboratory for diagnosis to detect FMD virus (O-A-C) in epithelia from animals affected by the disease. (author)

An Update on Biomedical Application of Nanotechnology for Alzheimer's Disease Diagnosis and Therapy.

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Panahi, Y; Mohammadhosseini, M; Abadi, A J N; Akbarzadeh, A; Mellatyar, H

2016-11-01

Approximately 35 million people worldwide suffer from Alzheimer's disease (AD). The cellular uptake and specific transport of drugs and imaging agents to brain are common issues in the diagnosis and therapy of AD. New advances in nanotechnology have supplied favorable solutions to this issue. Various nanocarriers such as polymeric nanoparticles, liposomes, micelles, dendrimers and nanogels have been studied for the delivery of drugs and imaging agents to brain. This review presents a succinct discussion of the applications of nanotechnology for Alzheimer's disease diagnosis and therapy. © Georg Thieme Verlag KG Stuttgart · New York.

Rheumatic diseases of the spine: imaging diagnosis.

Science.gov (United States)

Narváez, J A; Hernández-Gañán, J; Isern, J; Sánchez-Fernández, J J

2016-04-01

Spinal involvement is common both in the spondyloarthritides and in rheumatoid arthritis, in which the cervical segment is selectively affected. Rheumatoid involvement of the cervical spine has characteristic radiologic manifestations, fundamentally different patterns of atlantoaxial instability. Magnetic resonance imaging (MRI) is the technique of choice for evaluating the possible repercussions of atlantoaxial instability on the spinal cord and/or nerve roots in patients with rheumatoid arthritis as well as for evaluating parameters indicative of active inflammation, such as bone edema and synovitis. Axial involvement is characteristic in the spondyloarthritides and has distinctive manifestations on plain-film X-rays, which reflect destructive and reparative phenomena. The use of MRI has changed the conception of spondyloarthritis because it is able to directly detect the inflammatory changes that form part of the disease, making it possible to establish the diagnosis early in the disease process, when plain-film X-ray findings are normal (non-radiographic axial spondyloarthritis), to assess the prognosis of the disease, and to contribute to treatment planning. Copyright © 2016 SERAM. Published by Elsevier España, S.L.U. All rights reserved.

Implicit sequence learning in people with Parkinson’s disease

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Katherine R Gamble

2014-08-01

Full Text Available Implicit sequence learning involves learning about dependencies in sequences of events without intent to learn or awareness of what has been learned. Sequence learning is related to striatal dopamine levels, striatal activation, and integrity of white matter connections. People with Parkinson’s disease (PD have degeneration of dopamine-producing neurons, leading to dopamine deficiency and therefore striatal deficits, and they have difficulties with sequencing, including complex language comprehension and postural stability. Most research on implicit sequence learning in PD has used motor-based tasks. However, because PD presents with motor deficits, it is difficult to assess whether learning itself is impaired in these tasks. The present study used an implicit sequence learning task with a reduced motor component, the Triplets Learning Task (TLT. People with PD and age- and education-matched healthy older adults completed three sessions (each consisting of 10 blocks of 50 trials of the TLT. Results revealed that the PD group was able to learn the sequence, however, when learning was examined using a Half Blocks analysis (Nemeth et al., 2013, which compared learning in the 1st 25/50 trials of all blocks to that in the 2nd 25/50 trials, the PD group showed significantly less learning than Controls in the 2nd Half Blocks, but not in the 1st. Nemeth et al. hypothesized that the 1st Half Blocks involve recall and reactivation of the sequence learned, thus reflecting hippocampal-dependent learning, while the 2nd Half Blocks involve proceduralized behavior of learned sequences, reflecting striatal-based learning. The present results suggest that the PD group had intact hippocampal-dependent implicit sequence learning, but impaired striatal-dependent learning. Thus, sequencing deficits in PD are likely due to striatal impairments, but other brain systems, such as the hippocampus, may be able to partially compensate for striatal decline to improve

[Medical interviewing, initial key step in the disease diagnosis].

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Scheen, A J

2013-11-01

Medicine combines the characteristics of both a science and an art. The main objective is to cure the patient (or at least to alleviate symptoms). The first step of the global medical approach is to make a diagnosis, which will determine the therapy. Since Hippocrates, semiology, i.e. the study of both symptoms and signs, is crucial to make or guide the disease diagnosis. The development of more and more sophisticated medical technologies may lead to believe that semiology is not useful anymore in medical practice. It is absolutely not true because a careful semiology can provide precise diagnoses in a majority of cases or, at least, can lead to a limited differential diagnosis that helps in the selection of a few well defined complementary investigations. The aim of this article targeting mainly medical students is to emphasize the key rules of a well done medical interviewing, which should progress from an "analytical" approach to a "syndromic" approach, combining knowledge, know-how and self-management skills.

Noninvasive diagnosis of chronic kidney diseases using urinary proteome analysis

DEFF Research Database (Denmark)

Siwy, Justyna; Zürbig, Petra; Argilés, Angel

2017-01-01

BACKGROUND: In spite of its invasive nature and risks, kidney biopsy is currently required for precise diagnosis of many chronic kidney diseases (CKDs). Here, we explored the hypothesis that analysis of the urinary proteome can discriminate different types of CKD irrespective of the underlying me...

An intelligent medical system for diagnosis of bone diseases

Energy Technology Data Exchange (ETDEWEB)

Hatzilygeroudis, I [University of Patras, School of Engineering, Department of Computer Engineering and Informatics, 26500 Patras, Greece (Greece); Vassilakos, P J [Regional University Hospital of Patras, Department of Nuclear Medicine, Patras Greece (Greece); Tsakalidis, A [Computer Technology Institute, P.O. Box 1122, 26110 Patras, Greece (Greece)

1994-12-31

In this paper, aspects of the design of an intelligent medical system for diagnosis of bone diseases that can be detected by scintigraphic images are presented. The system comprises three major parts: a user interface (UI), a database management system (DBMS), and an expert system (ES). The DBMS is used for manipulation of various patient data. A number of patient cases are selected as prototype and stored in separate database. Diagnosis is performed via the ES, called XBONE, based on patient data. Knowledge is represented via an integrated formalism that combines production rules and a neural network. This results in better representation, and facilitates knowledge acquisition and maintenance. (authors). 10 refs., 2 figs.

Multiplex PCR for rapid diagnosis and differentiation of pox and pox-like diseases in dromedary Camels.

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Khalafalla, Abdelmalik I; Al-Busada, Khalid A; El-Sabagh, Ibrahim M

2015-07-07

Pox and pox-like diseases of camels are a group of exanthematous skin conditions that have become increasingly important economically. Three distinct viruses may cause them: camelpox virus (CMLV), camel parapox virus (CPPV) and camelus dromedary papilloma virus (CdPV). These diseases are often difficult to differentiate based on clinical presentation in disease outbreaks. Molecular methods such as PCR targeting species-specific genes have been developed and used to identify these diseases, but not simultaneously in a single tube. Recently, multiplex PCR has gained reputation as a convenient diagnostic method with cost-and timesaving benefits. In the present communication, we describe the development, optimization and validation of a multiplex PCR assay able to detect simultaneously the genome of the three viruses in one single test allowing for rapid and efficient molecular diagnosis. The assay was developed based on the evaluation and combination of published and new primer sets and was validated with viral genomic DNA extracted from known virus strains (n = 14) and DNA extracted from homogenized clinical skin specimens (n = 86). The assay detects correctly the target pathogens by amplification of targeted genes, even in case of co-infection. The method showed high sensitivity, and the specificity was confirmed by PCR-product sequencing. This assay provide rapid, sensitive and specific method for identifying three important viruses in specimens collected from dromedary camels with varying clinical presentations.

Use of Whole Genome Sequencing for Diagnosis and Discovery in the Cancer Genetics Clinic

Directory of Open Access Journals (Sweden)

Samantha B. Foley

2015-01-01

Full Text Available Despite the potential of whole-genome sequencing (WGS to improve patient diagnosis and care, the empirical value of WGS in the cancer genetics clinic is unknown. We performed WGS on members of two cohorts of cancer genetics patients: those with BRCA1/2 mutations (n = 176 and those without (n = 82. Initial analysis of potentially pathogenic variants (PPVs, defined as nonsynonymous variants with allele frequency < 1% in ESP6500 in 163 clinically-relevant genes suggested that WGS will provide useful clinical results. This is despite the fact that a majority of PPVs were novel missense variants likely to be classified as variants of unknown significance (VUS. Furthermore, previously reported pathogenic missense variants did not always associate with their predicted diseases in our patients. This suggests that the clinical use of WGS will require large-scale efforts to consolidate WGS and patient data to improve accuracy of interpretation of rare variants. While loss-of-function (LoF variants represented only a small fraction of PPVs, WGS identified additional cancer risk LoF PPVs in patients with known BRCA1/2 mutations and led to cancer risk diagnoses in 21% of non-BRCA cancer genetics patients after expanding our analysis to 3209 ClinVar genes. These data illustrate how WGS can be used to improve our ability to discover patients' cancer genetic risks.

Clinical and imaging diagnosis of IgG4-related disease in the head and neck

International Nuclear Information System (INIS)

Yu Changliang; Liu Bin; Yu Yongqiang

2013-01-01

IgG4-related disease in the head and neck is a newly recognized multi-organ system disease characterized by elevated serum IgG4, infiltration of numerous IgG4-positive plasma cells, tissue fibrosis, and dramatic response to corticosteroid treatment. IgG4-related disease of the head and neck has some relative characteristics on CT and MRI, which can provide valuable information for the diagnosis and differential diagnosis, and are helpful for the clinical treatment, evaluation of therapeutic effects and prediction of prognosis. (authors)

Emulation of Physician Tasks in Eye-Tracked Virtual Reality for Remote Diagnosis of Neurodegenerative Disease.

Science.gov (United States)

Orlosky, Jason; Itoh, Yuta; Ranchet, Maud; Kiyokawa, Kiyoshi; Morgan, John; Devos, Hannes

2017-04-01

For neurodegenerative conditions like Parkinson's disease, early and accurate diagnosis is still a difficult task. Evaluations can be time consuming, patients must often travel to metropolitan areas or different cities to see experts, and misdiagnosis can result in improper treatment. To date, only a handful of assistive or remote methods exist to help physicians evaluate patients with suspected neurological disease in a convenient and consistent way. In this paper, we present a low-cost VR interface designed to support evaluation and diagnosis of neurodegenerative disease and test its use in a clinical setting. Using a commercially available VR display with an infrared camera integrated into the lens, we have constructed a 3D virtual environment designed to emulate common tasks used to evaluate patients, such as fixating on a point, conducting smooth pursuit of an object, or executing saccades. These virtual tasks are designed to elicit eye movements commonly associated with neurodegenerative disease, such as abnormal saccades, square wave jerks, and ocular tremor. Next, we conducted experiments with 9 patients with a diagnosis of Parkinson's disease and 7 healthy controls to test the system's potential to emulate tasks for clinical diagnosis. We then applied eye tracking algorithms and image enhancement to the eye recordings taken during the experiment and conducted a short follow-up study with two physicians for evaluation. Results showed that our VR interface was able to elicit five common types of movements usable for evaluation, physicians were able to confirm three out of four abnormalities, and visualizations were rated as potentially useful for diagnosis.

Diagnosis of gluten related disorders: Celiac disease, wheat allergy and non-celiac gluten sensitivity.

Science.gov (United States)

Elli, Luca; Branchi, Federica; Tomba, Carolina; Villalta, Danilo; Norsa, Lorenzo; Ferretti, Francesca; Roncoroni, Leda; Bardella, Maria Teresa

2015-06-21

Cereal crops and cereal consumption have had a vital role in Mankind's history. In the recent years gluten ingestion has been linked with a range of clinical disorders. Gluten-related disorders have gradually emerged as an epidemiologically relevant phenomenon with an estimated global prevalence around 5%. Celiac disease, wheat allergy and non-celiac gluten sensitivity represent different gluten-related disorders. Similar clinical manifestations can be observed in these disorders, yet there are peculiar pathogenetic pathways involved in their development. Celiac disease and wheat allergy have been extensively studied, while non-celiac gluten sensitivity is a relatively novel clinical entity, believed to be closely related to other gastrointestinal functional syndromes. The diagnosis of celiac disease and wheat allergy is based on a combination of findings from the patient's clinical history and specific tests, including serology and duodenal biopsies in case of celiac disease, or laboratory and functional assays for wheat allergy. On the other hand, non-celiac gluten sensitivity is still mainly a diagnosis of exclusion, in the absence of clear-cut diagnostic criteria. A multimodal pragmatic approach combining findings from the clinical history, symptoms, serological and histological tests is required in order to reach an accurate diagnosis. A thorough knowledge of the differences and overlap in clinical presentation among gluten-related disorders, and between them and other gastrointestinal disorders, will help clinicians in the process of differential diagnosis.

Application of spectral computed tomography in diagnosis of liver and gallbladder diseases

Directory of Open Access Journals (Sweden)

LI Bolong

2017-03-01

Full Text Available Spectral computed tomography (CT is a perfect combination of diamond probe and strong computer processing technology and a technological revolution of traditional CT. This article reviews the application of spectral CT in the diagnosis of liver and gallbladder diseases. It summarizes the application value of monochromatic spectral CT imaging, spectral curve, material separation and quantitation, and effective atomic number in the diagnosis and differentiation of liver and gallbladder diseases and analyze the advantages of energy spectrum in identification of small lesions, low dose, and judgment of homology. It is pointed out that the application of spectral CT can be further explored in the aspects of early identification, differentiation, and prognosis of tumors.

Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease.

Science.gov (United States)

Dilliott, Allison A; Farhan, Sali M K; Ghani, Mahdi; Sato, Christine; Liang, Eric; Zhang, Ming; McIntyre, Adam D; Cao, Henian; Racacho, Lemuel; Robinson, John F; Strong, Michael J; Masellis, Mario; Bulman, Dennis E; Rogaeva, Ekaterina; Lang, Anthony; Tartaglia, Carmela; Finger, Elizabeth; Zinman, Lorne; Turnbull, John; Freedman, Morris; Swartz, Rick; Black, Sandra E; Hegele, Robert A

2018-04-04

Next-generation sequencing (NGS) is quickly revolutionizing how research into the genetic determinants of constitutional disease is performed. The technique is highly efficient with millions of sequencing reads being produced in a short time span and at relatively low cost. Specifically, targeted NGS is able to focus investigations to genomic regions of particular interest based on the disease of study. Not only does this further reduce costs and increase the speed of the process, but it lessens the computational burden that often accompanies NGS. Although targeted NGS is restricted to certain regions of the genome, preventing identification of potential novel loci of interest, it can be an excellent technique when faced with a phenotypically and genetically heterogeneous disease, for which there are previously known genetic associations. Because of the complex nature of the sequencing technique, it is important to closely adhere to protocols and methodologies in order to achieve sequencing reads of high coverage and quality. Further, once sequencing reads are obtained, a sophisticated bioinformatics workflow is utilized to accurately map reads to a reference genome, to call variants, and to ensure the variants pass quality metrics. Variants must also be annotated and curated based on their clinical significance, which can be standardized by applying the American College of Medical Genetics and Genomics Pathogenicity Guidelines. The methods presented herein will display the steps involved in generating and analyzing NGS data from a targeted sequencing panel, using the ONDRISeq neurodegenerative disease panel as a model, to identify variants that may be of clinical significance.

Post-mortem diagnosis of chronic Chagas's disease comparative evaluation of three serological tests on pericardial fluid.

Science.gov (United States)

Lopes, E R; Chapadeiro, E; Batista, S M; Cunha, J G; Rocha, A; Miziara, L; Ribeiro, J U; Patto, R J

1978-01-01

In an attempt to improve the post-mortem diagnosis of Chagas's disease the authors performed haemagglutination tests (HAT), fluorescent Trypanosoma cruzi antibody tests (FAT), and complement fixation tests (CFT) on the pericardial fluid obtained at autopsy of 50 individuals with Chagas's heart disease, and 93 patients in whom this disease was not thought to be present. The results demonstrate that all three tests are efficient for the post-mortem diagnosis of Chagas's disease but suggest that their combined use would detect more cases than would one isolated reaction only.

Ultrasound diagnosis of pulmonary hypertension in children with chronic bronchopulmonary diseases

International Nuclear Information System (INIS)

Kondrat'ev, V.O.

2000-01-01

Ultrasound criteria of diagnosis of pulmonary hypertension and study this complication frequency in children with chronic bronchopulmonary diseases was determined. As diagnostic criteria of pulmonary hypertension Doppler echocardiographic indices of circulation in the pulmonary arteries are suggested

The potential of radiologic procedures in the diagnosis of inflammatory bowel disease

Directory of Open Access Journals (Sweden)

S. E. Dubrova

2016-01-01

Full Text Available At present, there is no "golden standard" of diagnosis of inflammatory bowel disease. Each and every individual case requires a thorough analysis of clinical symptoms in their association with endoscopic, histological, radiological and laboratory data. This review paper analyzes both conventional and novel methods of radiological investigations. Some of them have changed their significance from the "golden standard" to rare and limited application and from promising, then frequent and currently sporadic use of small bowel enema. Traditional ileocolonoscopy maintains its diagnostic potential, especially as a tool for follow up of patients with colonic and ileac disorders. The state-of-the-art non-invasive (ultrasound examination and limitedly non-invasive (computerized tomography and magnetic resonance imaging procedures are considered to be the most accurate methods for assessment of inflammatory bowel disorders in patient with already confirmed diagnosis and those with suspected cases of Crohn's disease and ulcerative colitis. The paper describes preparation of patient for each method, assessment technique, advantages and limitations for use, diagnostic criteria for intestinal wall thickness, accuracy of methods and discusses the perspectives of their use. The main sign of inflammatory bowel disease is thickening of intestinal wall. Usually its mean thickness in Crohn's disease (11 to 13 mm is higher than that in ulcerative colitis (7 to 8 mm. This may provide a diagnostic key during differential diagnosis of an isolated colon disease. The amount of the contrast cumulated by the intestinal wall directly correlates with inflammation activity. Intensive contract cumulation in the intestinal wall after intravenous contrast enhancement is a symptom of active inflammatory process. However, despite progression in the technologies, initial signs of inflammatory bowel diseases are quite superficial and remain hardly visible, being below the resolution

Association between Age at Diagnosis of Graves' Disease and Variants in Genes Involved in Immune Response

Science.gov (United States)

Jurecka-Lubieniecka, Beata; Ploski, Rafal; Kula, Dorota; Krol, Aleksandra; Bednarczuk, Tomasz; Kolosza, Zofia; Tukiendorf, Andrzej; Szpak-Ulczok, Sylwia; Stanjek-Cichoracka, Anita; Polanska, Joanna; Jarzab, Barbara

2013-01-01

Background Graves' disease (GD) is a complex disease in which genetic predisposition is modified by environmental factors. The aim of the study was to examine the association between genetic variants in genes encoding proteins involved in immune response and the age at diagnosis of GD. Methods 735 GD patients and 1216 healthy controls from Poland were included into the study. Eight genetic variants in the HLA-DRB1, TNF, CTLA4, CD40, NFKb, PTPN22, IL4 and IL10 genes were genotyped. Patients were stratified by the age at diagnosis of GD and the association with genotype was analysed. Results Polymorphism in the HLA-DRB1, TNF and CTLA4 genes were associated with GD. The carriers of the HLA DRB1*03 allele were more frequent in patients with age at GD diagnosis ≤30 years than in patients with older age at GD diagnosis. Conclusions HLADRB1*03 allele is associated with young age at diagnosis of Graves' disease in polish population. PMID:23544060

Preimplantation Genetic Diagnosis: Prenatal Testing for Embryos Finally Achieving Its Potential

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Harvey J. Stern

2014-03-01

Full Text Available Preimplantation genetic diagnosis was developed nearly a quarter-century ago as an alternative form of prenatal diagnosis that is carried out on embryos. Initially offered for diagnosis in couples at-risk for single gene genetic disorders, such as cystic fibrosis, spinal muscular atrophy and Huntington disease, preimplantation genetic diagnosis (PGD has most frequently been employed in assisted reproduction for detection of chromosome aneuploidy from advancing maternal age or structural chromosome rearrangements. Major improvements have been seen in PGD analysis with movement away from older, less effective technologies, such as fluorescence in situ hybridization (FISH, to newer molecular tools, such as DNA microarrays and next generation sequencing. Improved results have also started to be seen with decreasing use of Day 3 blastomere biopsy in favor of polar body or Day 5 trophectoderm biopsy. Discussions regarding the scientific, ethical, legal and social issues surrounding the use of sequence data from embryo biopsy have begun and must continue to avoid concern regarding eugenic or inappropriate use of this technology.

Preimplantation Genetic Diagnosis: Prenatal Testing for Embryos Finally Achieving Its Potential

Science.gov (United States)

Stern, Harvey J.

2014-01-01

Preimplantation genetic diagnosis was developed nearly a quarter-century ago as an alternative form of prenatal diagnosis that is carried out on embryos. Initially offered for diagnosis in couples at-risk for single gene genetic disorders, such as cystic fibrosis, spinal muscular atrophy and Huntington disease, preimplantation genetic diagnosis (PGD) has most frequently been employed in assisted reproduction for detection of chromosome aneuploidy from advancing maternal age or structural chromosome rearrangements. Major improvements have been seen in PGD analysis with movement away from older, less effective technologies, such as fluorescence in situ hybridization (FISH), to newer molecular tools, such as DNA microarrays and next generation sequencing. Improved results have also started to be seen with decreasing use of Day 3 blastomere biopsy in favor of polar body or Day 5 trophectoderm biopsy. Discussions regarding the scientific, ethical, legal and social issues surrounding the use of sequence data from embryo biopsy have begun and must continue to avoid concern regarding eugenic or inappropriate use of this technology. PMID:26237262

MRI of sporadic Creutzfeldt-Jakob disease

International Nuclear Information System (INIS)

Kong, A.; Vliet, A. Van der.

2008-01-01

Full text: The key MRI findings in five cases of sporadic Creutzfeldt-Jakob disease (CJD) are illustrated with four 'definite' and one 'probable' according to World Health Organization criteria. Close attention to fluid-attenuation inversion recovery and diffusion-weighted imaging sequences are important for diagnosis, noting especially restricted diffusion in cortical and deep grey matter. Our study and those of others show predominant cortical, caudate and thalamic involvement. This pattern is highly sensitive and specific for the diagnosis. Fluid-attenuation inversion recovery and diffusion-weighted imaging signal abnormality becomes progressively more extensive and bilateral as disease progresses, but may become less pronounced in end-stage disease because of atrophy.

Application of high-throughput sequencing in understanding human oral microbiome related with health and disease

OpenAIRE

Chen, Hui; Jiang, Wen

2014-01-01

The oral microbiome is one of most diversity habitat in the human body and they are closely related with oral health and disease. As the technique developing,, high throughput sequencing has become a popular approach applied for oral microbial analysis. Oral bacterial profiles have been studied to explore the relationship between microbial diversity and oral diseases such as caries and periodontal disease. This review describes the application of high-throughput sequencing for characterizati...

Genetics of Infectious and Inflammatory Diseases: Overlapping Discoveries from Association and Exome-Sequencing Studies.

Science.gov (United States)

Langlais, David; Fodil, Nassima; Gros, Philippe

2017-04-26

Genome technologies have defined a complex genetic architecture in major infectious, inflammatory, and autoimmune disorders. High density marker arrays and Immunochips have powered genome-wide association studies (GWAS) that have mapped nearly 450 genetic risk loci in 22 major inflammatory diseases, including a core of common genes that play a central role in pathological inflammation. Whole-exome and whole-genome sequencing have identified more than 265 genes in which mutations cause primary immunodeficiencies and rare forms of severe inflammatory bowel disease. Combined analysis of inflammatory disease GWAS and primary immunodeficiencies point to shared proteins and pathways that are required for immune cell development and protection against infections and are also associated with pathological inflammation. Finally, sequencing of chromatin immunoprecipitates containing specific transcription factors, with parallel RNA sequencing, has charted epigenetic regulation of gene expression by proinflammatory transcription factors in immune cells, providing complementary information to characterize morbid genes at infectious and inflammatory disease loci.

Application of L1/2 regularization logistic method in heart disease diagnosis.

Science.gov (United States)

Zhang, Bowen; Chai, Hua; Yang, Ziyi; Liang, Yong; Chu, Gejin; Liu, Xiaoying

2014-01-01

Heart disease has become the number one killer of human health, and its diagnosis depends on many features, such as age, blood pressure, heart rate and other dozens of physiological indicators. Although there are so many risk factors, doctors usually diagnose the disease depending on their intuition and experience, which requires a lot of knowledge and experience for correct determination. To find the hidden medical information in the existing clinical data is a noticeable and powerful approach in the study of heart disease diagnosis. In this paper, sparse logistic regression method is introduced to detect the key risk factors using L(1/2) regularization on the real heart disease data. Experimental results show that the sparse logistic L(1/2) regularization method achieves fewer but informative key features than Lasso, SCAD, MCP and Elastic net regularization approaches. Simultaneously, the proposed method can cut down the computational complexity, save cost and time to undergo medical tests and checkups, reduce the number of attributes needed to be taken from patients.

Statistical guidance for experimental design and data analysis of mutation detection in rare monogenic mendelian diseases by exome sequencing.

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Degui Zhi

Full Text Available Recently, whole-genome sequencing, especially exome sequencing, has successfully led to the identification of causal mutations for rare monogenic Mendelian diseases. However, it is unclear whether this approach can be generalized and effectively applied to other Mendelian diseases with high locus heterogeneity. Moreover, the current exome sequencing approach has limitations such as false positive and false negative rates of mutation detection due to sequencing errors and other artifacts, but the impact of these limitations on experimental design has not been systematically analyzed. To address these questions, we present a statistical modeling framework to calculate the power, the probability of identifying truly disease-causing genes, under various inheritance models and experimental conditions, providing guidance for both proper experimental design and data analysis. Based on our model, we found that the exome sequencing approach is well-powered for mutation detection in recessive, but not dominant, Mendelian diseases with high locus heterogeneity. A disease gene responsible for as low as 5% of the disease population can be readily identified by sequencing just 200 unrelated patients. Based on these results, for identifying rare Mendelian disease genes, we propose that a viable approach is to combine, sequence, and analyze patients with the same disease together, leveraging the statistical framework presented in this work.

Near-complete genome sequencing of swine vesicular disease virus using the Roche GS FLX sequencing platform

DEFF Research Database (Denmark)

Nielsen, Sandra Cathrine Abel; Bruhn, Christian Anders Wathne; Samaniego Castruita, Jose Alfredo

2014-01-01

Swine vesicular disease virus (SVDV) is an enterovirus that is both genetically and antigenically closely related to human coxsackievirus B5 within the Picornaviridae family. SVDV is the causative agent of a highly contagious (though rarely fatal) vesicular disease in pigs. We report a rapid method...... with significant genetic distances within the same species of viruses. All reference mappings used an iterative method to avoid bias. Further verification was achieved through phylogenetic analysis against published SVDV genomes and additional Enterovirus B sequences. This approach allows high confidence...

Autosomal Recessive Polycystic Kidney Disease: Antenatal Diagnosis and Histopathological Correlation

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Dayananda Kumar Rajanna

2013-01-01

Full Text Available Autosomal recessive polycystic kidney disease (ARPKD is one of the most common inheritable disease manifesting in infancy and childhood with a frequency of 1:6,000 to 1:55,000 births. The patient in her second trimester presented with a history of amenorrhea. Ultrasound examination revealed bilateral, enlarged, hyperechogenic kidneys, placentomegaly, and severe oligohydramnios. The pregnancy was terminated. An autopsy was performed on the fetus. Both the kidneys were found to be enlarged and the cut surface showed numerous cysts. The liver sections showed changes due to fibrosis. The final diagnosis of autosomal recessive polycystic kidney disease was made based on these findings. In this article, we correlate the ante-natal ultrasound and histopathological findings in autosomal recessive polycystic kidney disease.

Inter-observer variation of diagnosis of Alzheimer's disease by SPECT

International Nuclear Information System (INIS)

Oshima, Motoo; Machida, Kikuo; Koizumi, Kiyoshi

2001-01-01

SPECT shows characteristic distribution in Alzheimer's disease. The purpose of this study is to define inter-observer variations in the diagnosis of Alzheimer's disease. Fifty-seven patients, included 19 Alzheimer's disease were collected from four institutions. Five-graded score was used to interprete SPECT in 18 regions. Ten nuclear medicine physicians interpreted SPECT referred with MMSE and clinical information. Among 57 cases 19 Alzheimer's disease were selected in this study. Statistics were performed between SPECT score and MMSE score. In conclusion, inter-observer variation is present in SPECT interpretation. There was a good correlation SPECT and MMSE with proper brain SPECT physicians. They are superior to in the interpretation not only resident, but other specialists. Education in the interpretation of brain SPECT looks important. (author)

Biomarkers in the Diagnosis and Prognosis of Alzheimer's Disease.

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Schaffer, Cole; Sarad, Nakia; DeCrumpe, Ashton; Goswami, Disha; Herrmann, Sara; Morales, Jose; Patel, Parth; Osborne, Jim

2015-10-01

Alzheimer's disease (AD) is a neurodegenerative disease that inhibits cognitive functions and has no cure. This report reviews the current diagnostic standards for AD with an emphasis on early diagnosis using the cerebrospinal fluid (CSF) biomarkers amyloid-beta, t-tau, and p-tau and fluorodeoxyglucose positron emission tomography imaging. Abnormal levels of these CSF biomarkers and decreased cerebral uptake of glucose have recently been used in the early diagnosis of AD in experimental studies. These promising biomarkers can be measured using immunoassays performed in singleplex or multiplex formats. Although presently, there are no Food and Drug Administration-approved in vitro diagnostics (IVDs) for early detection of AD, a multiplex immunoassay measuring a panel of promising AD biomarkers in CSF may be a likely IVD candidate for the clinical AD diagnostic market. Specifically, the INNO-BIA AlzBio3 immunoassay kit, performed using bead arrays on the xMAP Luminex analyzer, allows simultaneous quantification of amyloid-beta, t-tau, and p-tau biomarkers. AD biomarkers can also be screened using enzyme-linked immunosorbent assays that are offered as laboratory-developed tests. © 2014 Society for Laboratory Automation and Screening.

Cognitive and behavioral changes in Huntington disease before diagnosis.

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Paulsen, Jane S; Miller, Amanda C; Hayes, Terry; Shaw, Emily

2017-01-01

Phenotypic manifestations of Huntington disease (HD) can be detected at least 15 years prior to the time when a motor diagnosis is given. Advances in clinical care and future research will require consistent use of HD definitions and HD premanifest (prodromal) stages being used across clinics, sites, and countries. Cognitive and behavioral (psychiatric) changes in HD are summarized and implications for ongoing advancement in our knowledge of prodromal HD are suggested. The earliest detected cognitive changes are observed in the Symbol Digit Modalities Test, Stroop Interference, Stroop Color and Word Test-interference condition, and Trail Making Test. Cognitive changes in the middle and near motor diagnostic stages of prodromal HD involve nearly every cognitive test administered and the greatest changes over time (i.e., slopes) are found in those prodromal HD participants who are nearest to motor diagnosis. Psychiatric changes demonstrate significant worsening over time and remain elevated compared with healthy controls throughout the prodromal disease course. Psychiatric and behavior changes in prodromal HD are much lower than that obtained using cognitive assessment, although the psychiatric and behavioral changes represent symptoms most debilitating to independent capacity and wellness. Copyright © 2017 Elsevier B.V. All rights reserved.

Laboratory diagnosis of tick-borne African relapsing fevers: latest developments

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Aurélien eFotso Fotso

2015-11-01

Full Text Available In Africa, relapsing fevers caused by ectoparasite-borne Borrelia species are transmitted by ticks, with the exception of Borrelia recurrentis, which is a louse-borne spirochete. These tropical diseases responsible for mild to deadly spirochetemia. Cultured B. crocidurae, B. duttonii and B. hispanica circulate alongside at least six species which have not yet been cultured in vectors. Direct diagnosis is hindered by the use of non-specific laboratory tools. Indeed, microscopic observation of Borrelia spirochaeta in smears of peripheral blood taken from febrile patients lacks sensitivity and specificity. Although best visualised using dark-field microscopy, the organisms can also be detected using Wright-Giemsa or acridine orange stains.. PCR-based detection of specific sequences in total DNA extracted from a specimen can be used to discriminate different relapsing fever Borreliae. In our laboratory, we developed a multiplex real-time PCR assay for the specific detection of B. duttonii/recurrentis and B. crocidurae: Multispacer Sequence Typing accurately identified cultured relapsing fever borreliae and revealed diversity among them. Other molecular typing techniques, such as multilocus sequence analysis of tick-borne relapsing fever borreliae, showed the potential risk of human infection in Africa. Recent efforts to culture and sequence relapsing fever borreliae have provided new information for reassessment of the diversity of these bacteria. Recently, matrix-assisted laser desorption ionization time-of-flight mass spectrometry has been reported as a means of identifying cultured borreliae and of identifying both vectors and vectorised pathogens such as detecting relapsing fever borreliae directly in ticks. The lack of a rapid diagnosis test restricts the management of such diseases. We produced monoclonal antibodies against Borrelia crocidurae in order to develop cheap assays for the rapid detection of relapsing fever borreliae. In this paper

Intelligence system based classification approach for medical disease diagnosis

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Sagir, Abdu Masanawa; Sathasivam, Saratha

2017-08-01

The prediction of breast cancer in women who have no signs or symptoms of the disease as well as survivability after undergone certain surgery has been a challenging problem for medical researchers. The decision about presence or absence of diseases depends on the physician's intuition, experience and skill for comparing current indicators with previous one than on knowledge rich data hidden in a database. This measure is a very crucial and challenging task. The goal is to predict patient condition by using an adaptive neuro fuzzy inference system (ANFIS) pre-processed by grid partitioning. To achieve an accurate diagnosis at this complex stage of symptom analysis, the physician may need efficient diagnosis system. A framework describes methodology for designing and evaluation of classification performances of two discrete ANFIS systems of hybrid learning algorithms least square estimates with Modified Levenberg-Marquardt and Gradient descent algorithms that can be used by physicians to accelerate diagnosis process. The proposed method's performance was evaluated based on training and test datasets with mammographic mass and Haberman's survival Datasets obtained from benchmarked datasets of University of California at Irvine's (UCI) machine learning repository. The robustness of the performance measuring total accuracy, sensitivity and specificity is examined. In comparison, the proposed method achieves superior performance when compared to conventional ANFIS based gradient descent algorithm and some related existing methods. The software used for the implementation is MATLAB R2014a (version 8.3) and executed in PC Intel Pentium IV E7400 processor with 2.80 GHz speed and 2.0 GB of RAM.

Acute bone crises in sickle cell disease: the T1 fat-saturated sequence in differentiation of acute bone infarcts from acute osteomyelitis

International Nuclear Information System (INIS)

Jain, R.; Sawhney, S.; Rizvi, S.G.

2008-01-01

Aim: To prove the hypothesis that acute bone infarcts in sickle cell disease are caused by sequestration of red blood cells (RBCs) in bone marrow, and to evaluate the unenhanced T1 fat-saturated (fs) sequence in the differentiation of acute bone infarction from acute osteomyelitis in patients with sickle-cell disease. Materials and methods: Two studies were undertaken: an experimental study using in-vitro packed red blood cells and normal volunteers, and a retrospective clinical study of 86 magnetic resonance imaging (MRI) studies. For the experimental study containers of packed RBCs were placed between the knees of four healthy volunteers with a saline bag under the containers as an additional control, and were scanned with the pre-contrast T1-fs sequence. Signal intensity (SI) ratios were obtained for packed RBCs:skeletal muscle and packed RBCs:saline. For the clinical study, the SIs of normal bone marrow, packed RBCs, bone and/or soft-tissue lesions, and normal skeletal muscle of 74 patients (86 MRI studies) were measured using unenhanced, T1 fat-saturated MRI. The ratios of the above SIs to normal skeletal muscle were calculated and subjected to statistical analysis. Results: Fifty-one of 86 MRI studies were included in the final analysis. The ratios of SIs for normal bone marrow, packed red cells, bone infarction, acute osteomyelitis, and soft-tissue lesions associated with bone infarct, compared with normal skeletal muscle were (mean ± SD) 0.9 ± 0.2, 2.1 ± 0.7, 1.7 ± 0.5, 1.0 ± 0.3, and 2.2 ± 0.7, respectively. The difference in the ratio of SIs of bone infarcts and osteomyelitis was significant (p = 0.003). The final diagnoses were bone infarction (n = 50), acute osteomyelitis (n = 1), and co-existent bone infarction and osteomyelitis (n = 2). Seven patients who had suspected osteomyelitis underwent image-guided aspiration. Conclusion: Acute bone infarcts in sickle cell disease are caused by sequestration of red blood cells in the bone marrow. The

Diagnosis of dry eye disease and emerging technologies

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Zeev, Maya Salomon-Ben; Miller, Darby Douglas; Latkany, Robert

2014-01-01

Dry eye is one of the most commonly encountered problems in ophthalmology. Signs can include punctate epithelial erosions, hyperemia, low tear lakes, rapid tear break-up time, and meibomian gland disease. Current methods of diagnosis include a slit-lamp examination with and without different stains, including fluorescein, rose bengal, and lissamine green. Other methods are the Schirmer test, tear function index, tear break-up time, and functional visual acuity. Emerging technologies include meniscometry, optical coherence tomography, tear film stability analysis, interferometry, tear osmolarity, the tear film normalization test, ocular surface thermography, and tear biomarkers. Patient-specific considerations involve relevant history of autoimmune disease, refractive surgery or use of oral medications, and allergies or rosacea. Other patient considerations include clinical examination for lid margin disease and presence of lagophthalmos or blink abnormalities. Given a complex presentation and a variety of signs and symptoms, it would be beneficial if there was an inexpensive, readily available, and reproducible diagnostic test for dry eye. PMID:24672224

Differential Diagnosis of the pancreatic disease : significance of perivascular changes at celiac trunk and superior mesenteric artery on CT

Energy Technology Data Exchange (ETDEWEB)

Kwon, Ryang; Kim, Ki Whang; Yu, Jeong Sik; Kim, Ji Hyung; Kim, Dong Guk; Lee, Sung Il; Ahn, Chang Soo; Oh, Sei Jung [Yonsei Univ., Seoul (Korea, Republic of). Coll. of Medicine; Kim, Young Hwan [Sanggye Paik Hospital, Seoul (Korea, Republic of)

1998-03-01

The purpose of this paper is to classify perivascular change in the celiac trunk and SMA occurring in pancreatic disease and to evaluate its significance in differential diagnosis. In 73 patients with pancreatic disease (42, acute pancreatitis; 14, chronic pancreatitis; 17, pancreatic cancer) abdominal CT findings were retrospectively reviewed. We defined infiltration as linear or irregular density and thickening as presence of a soft tissue mantle surrounding the vessel, and statistically evaluated the usefulness of these factors for the differential diagnosis of pancreatic diseases. Thickening of the celiac trunk and SMA is a valuable finding in the differential diagnosis of pancreatic inflammatory disease and pancreatic cancer. When applied to the differential diagnosis of pancreatic disease, perivascular change should be classified as either infiltration or thickening. (author). 10 refs., 1 tab., 2 figs.

Differential Diagnosis of the pancreatic disease : significance of perivascular changes at celiac trunk and superior mesenteric artery on CT

International Nuclear Information System (INIS)

Kwon, Ryang; Kim, Ki Whang; Yu, Jeong Sik; Kim, Ji Hyung; Kim, Dong Guk; Lee, Sung Il; Ahn, Chang Soo; Oh, Sei Jung

1998-01-01

The purpose of this paper is to classify perivascular change in the celiac trunk and SMA occurring in pancreatic disease and to evaluate its significance in differential diagnosis. In 73 patients with pancreatic disease (42, acute pancreatitis; 14, chronic pancreatitis; 17, pancreatic cancer) abdominal CT findings were retrospectively reviewed. We defined infiltration as linear or irregular density and thickening as presence of a soft tissue mantle surrounding the vessel, and statistically evaluated the usefulness of these factors for the differential diagnosis of pancreatic diseases. Thickening of the celiac trunk and SMA is a valuable finding in the differential diagnosis of pancreatic inflammatory disease and pancreatic cancer. When applied to the differential diagnosis of pancreatic disease, perivascular change should be classified as either infiltration or thickening. (author). 10 refs., 1 tab., 2 figs

Norrie disease. Diagnosis of a simplex case by DNA analysis.

Science.gov (United States)

Chynn, E W; Walton, D S; Hahn, L B; Dryja, T P

1996-09-01

Norrie disease is a rare, X-linked recessive disorder characterized by congenital blindness due to malformed retinas. We describe a simplex patient who had leukokoria and whose clinical diagnosis was confirmed only after molecular genetics analysis. DNA analysis was also used to determine the carrier status of relatives of the proband.

Effectiveness of bronchoscopy in the diagnosis of bronchial-type mycobacterium avium-intracellulare complex pulmonary disease

International Nuclear Information System (INIS)

Sato, Kazuhiro; Kourakata, Hiroyo

2004-01-01

Mycobacterium avium-intracellulare complex (MAC) pulmonary disease with associated nodules and bronchiectasis is an increasingly prevalent condition. This condition is often difficult to diagnose in the early stages of the disease, because of the limited effectiveness of sputum culture cytology. The effectiveness of bronchoscopy in the isolation and diagnosis of MAC in respiratory secretions is still unclear. Over a three-year period, we examined the effectiveness of bronchoscopy in 45 non-HIV-infected patients who had clusters of small peripheral lung nodules. These nodules were associated with changes of the draining bronchi detected by high-resolution CT (HRCT). A total of 22 of 45 patients (48.9%) had cultures positive for MAC. In the MAC-positive group, 10 patients tested positive for disease in sputum and 22 tested positive for disease in bronchial washings. A total of 13 of 45 patients (28.9%) fulfilled the American Thoracic Society criteria for pulmonary MAC disease, and 9 (20.0%) others with cultures positive for MAC did not fulfill the criteria. Radiographic measures and sputum cultures of 13 of 16 patients (81.3%) with negative cultures revealed no further disease progression. We found that HRCT was a useful technique in the diagnosis of MAC-pulmonary disease. We also found that bronchoscopy was a more sensitive diagnostic technique than sputum culture, analysis in the differential diagnosis of MAC pulmonary diseases. (author)

Computer- Aided diagnosis system for the evaluation of chronic obstructive pulmonary disease on CT Images

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Parsa Hosseini M

2011-03-01

Full Text Available "n Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0cm 5.4pt 0cm 5.4pt; mso-para-margin:0cm; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:Arial; mso-bidi-theme-font:minor-bidi;} Background: Chronic Obstructive Pulmonary Disease (COPD is one of the most prevalent pulmonary diseases. Use of an automatic system for the detection and diagnosis of the disease will be beneficial to the patients' treatment decision-making process. In this paper, we propose a new approach for the Computer Aided Diagnosis (CAD of the disease and determination of its severity axial CT scan images."n"nMethods: In this study, 24 lung CT scans in full inspiratory and expiratory states were performed. Variations in the normalized pattern of the lungs' external parenchyma were exploited as a feature for COPD diagnosis. Subsequently, a Bayesian classifier was used to classify variations into two normal and abnormal patterns for the discrimination of patients and healthy individuals. Finally, the accuracy of the classification was assessed statistically. "n"nResults: With the proposed method, the lungs parenchymal elasticity and air-trapping were determined quantitatively. The more this feature tended to zero, the more severe air-trapping and obstructive pulmonary disease is. By analyzing CT images in the healthy and patient groups, we calculated the hard threshold for the diagnosis of the disease. Clinical results

Timely diagnosis of sitosterolemia by next generation sequencing in two children with severe hypercholesterolemia.

Science.gov (United States)

Buonuomo, Paola Sabrina; Iughetti, Lorenzo; Pisciotta, Livia; Rabacchi, Claudio; Papadia, Francesco; Bruzzi, Patrizia; Tummolo, Albina; Bartuli, Andrea; Cortese, Claudio; Bertolini, Stefano; Calandra, Sebastiano

2017-07-01

Severe hypercholesterolemia associated or not with xanthomas in a child may suggest the diagnosis of homozygous autosomal dominant hypercholesterolemia (ADH), autosomal recessive hypercholesterolemia (ARH) or sitosterolemia, depending on the transmission of hypercholesterolemia in the patient's family. Sitosterolemia is a recessive disorder characterized by high plasma levels of cholesterol and plant sterols due to mutations in the ABCG5 or the ABCG8 gene, leading to a loss of function of the ATP-binding cassette (ABC) heterodimer transporter G5-G8. We aimed to perform the molecular characterization of two children with severe primary hypercholesterolemia. Case #1 was a 2 year-old girl with high LDL-cholesterol (690 mg/dl) and tuberous and intertriginous xanthomas. Case #2 was a 7 year-old boy with elevated LDL-C (432 mg/dl) but no xanthomas. In both cases, at least one parent had elevated LDL-cholesterol levels. For the molecular diagnosis, we applied targeted next generation sequencing (NGS), which unexpectedly revealed that both patients were compound heterozygous for nonsense mutations: Case #1 in ABCG5 gene [p.(Gln251*)/p.(Arg446*)] and Case #2 in ABCG8 gene [p.(Ser107*)/p.(Trp361*)]. Both children had extremely high serum sitosterol and campesterol levels, thus confirming the diagnosis of sisterolemia. A low-fat/low-sterol diet was promptly adopted with and without the addition of ezetimibe for Case #1 and Case #2, respectively. In both patients, serum total and LDL-cholesterol decreased dramatically in two months and progressively normalized. Targeted NGS allows the rapid diagnosis of sitosterolemia in children with severe hypercholesterolemia, even though their family history does not unequivocally suggest a recessive transmission of hypercholesterolemia. A timely diagnosis is crucial to avoid delays in treatment. Copyright © 2017 Elsevier B.V. All rights reserved.

The Big Bluff of Amyotrophic Lateral Sclerosis Diagnosis: The Role of Neurodegenerative Disease Mimics.

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Bicchi, Ilaria; Emiliani, Carla; Vescovi, Angelo; Martino, Sabata

2015-01-01

Neurodegenerative diseases include a significant number of pathologies affecting the nervous system. Generally, the primary cause of each disease is specific; however, recently, it was shown that they may be correlated at molecular level. This aspect, together with the exhibition of similar symptoms, renders the diagnosis of these disorders difficult. Amyotrophic lateral sclerosis is one of these pathologies. Herein, we report several cases of amyotrophic lateral sclerosis misdiagnosed as a consequence of features that are common to several neurodegenerative diseases, such as Parkinson's, Huntington's and Alzheimer's disease, spinal muscular atrophy, progressive bulbar palsy, spastic paraplegia and frontotemporal dementia, and mostly with the lysosomal storage disorder GM2 gangliosidosis. Overall reports highlight that the differential diagnosis for amyotrophic lateral sclerosis should include correlated mechanisms. © 2015 S. Karger AG, Basel.

Information system for diagnosis of respiratory system diseases

Science.gov (United States)

Abramov, G. V.; Korobova, L. A.; Ivashin, A. L.; Matytsina, I. A.

2018-05-01

An information system is for the diagnosis of patients with lung diseases. The main problem solved by this system is the definition of the parameters of cough fragments in the monitoring recordings using a voice recorder. The authors give the recognition criteria of recorded cough moments, audio records analysis. The results of the research are systematized. The cough recognition system can be used by the medical specialists to diagnose the condition of the patients and to monitor the process of their treatment.

Fuzzy Computer-Aided Alzheimer's Disease Diagnosis Based on MRI Data.

Science.gov (United States)

Krashenyi, Igor; Ramírez, Javier; Popov, Anton; Górriz, Juan Manuel; The Alzheimer's Disease Neuroimaging Initiative

2016-01-01

Alzheimer's disease (AD) is a chronic neurodegenerative disease of the central nervous system that has no cure and leads to death. One of the most prevalent tools for AD diagnosis is magnetic resonance imaging (MRI), because of its capability to visualize brain anatomical structures. There is a variety of classification methods for automatic diagnosis of AD, such as support vector machines, genetic algorithms, Bayes classifiers, neural networks, random forests, etc., but none of them provides robust information about the stage of the AD, they can just reveal the presence of disease. In this paper, a new approach for classification of MRI images using a fuzzy inference system is proposed. Two statistical moments (mean and standard deviation) of 116 anatomical regions of interests (ROIs) are used as input features for the classification system. A t-test feature selection method is used to identify the most discriminative ROIs. In order to evaluate the proposed system, MRI images from a database consisting of 818 subjects (229 normal, 401 mild cognitive impairment and 188 AD subjects) collected from the Alzheimer's disease neuroimaging initiative (ADNI) is analyzed. The receiver operating characteristics (ROC) curve and the area under the curve (AUC) of the proposed fuzzy inference system fed by statistical input features are employed as the evaluation criteria with k-fold cross validation. The proposed system yields promising results in normal vs. AD classification with AUC of 0.99 on the training set and 0.8622±0.0033 on the testing set.

Diagnosis of gluten related disorders: Celiac disease, wheat allergy and non-celiac gluten sensitivity

Science.gov (United States)

Elli, Luca; Branchi, Federica; Tomba, Carolina; Villalta, Danilo; Norsa, Lorenzo; Ferretti, Francesca; Roncoroni, Leda; Bardella, Maria Teresa

2015-01-01

Cereal crops and cereal consumption have had a vital role in Mankind’s history. In the recent years gluten ingestion has been linked with a range of clinical disorders. Gluten-related disorders have gradually emerged as an epidemiologically relevant phenomenon with an estimated global prevalence around 5%. Celiac disease, wheat allergy and non-celiac gluten sensitivity represent different gluten-related disorders. Similar clinical manifestations can be observed in these disorders, yet there are peculiar pathogenetic pathways involved in their development. Celiac disease and wheat allergy have been extensively studied, while non-celiac gluten sensitivity is a relatively novel clinical entity, believed to be closely related to other gastrointestinal functional syndromes. The diagnosis of celiac disease and wheat allergy is based on a combination of findings from the patient’s clinical history and specific tests, including serology and duodenal biopsies in case of celiac disease, or laboratory and functional assays for wheat allergy. On the other hand, non-celiac gluten sensitivity is still mainly a diagnosis of exclusion, in the absence of clear-cut diagnostic criteria. A multimodal pragmatic approach combining findings from the clinical history, symptoms, serological and histological tests is required in order to reach an accurate diagnosis. A thorough knowledge of the differences and overlap in clinical presentation among gluten-related disorders, and between them and other gastrointestinal disorders, will help clinicians in the process of differential diagnosis. PMID:26109797

Diagnosis of Periodontal Diseases: Building a Bridge from Today's Methods to Tomorrow's Technology.

Science.gov (United States)

Jeffcoat, Marjorie K.

1994-01-01

A discussion of advancements in diagnosis of periodontal diseases looks first at the screening process, reviews specific periodontal diseases and their clinical signs and symptoms, and explains both traditional and newly developed diagnostic tests. A framework for understanding the tests' clinical usefulness is also presented. (MSE)

Application of Serum Hepatic Fibrosis Indices in the Diagnosis of Hepatic Disease

International Nuclear Information System (INIS)

Lu Yanting; Wang Taisong; Gu Xin

2010-01-01

To investigate the significance of combined detection of laminin (LN), collagen type IV (CIV), hyaluronic acid (HA) and precollagen type III (PCIII) in the diagnosis of hepatic fibrosis. The serum levels of LN, CIV, HA and PCIII in 143 patients with hepatic disease and 41 healthy controls were measured by radioimmunoassay (RIA). The results showed that the serum levels of LN, CIV, HA and PCIII in patients with hepatic disease were significantly higher than those of the control group (P<0.01), and the serum levels of those markers were related to the severity of the chronic hepatic disease. The highest serum levels were found in serious chronic hepatitis group and hepatic fibrosis group,and the increase of serum HA and PCIII was most remarkable. Combined detection of LN, CIV, HA and PCIII is a sensitive and reliable method in the diagnosis of hepatic fibrosis, but the four serum indices can not be used in differentiating serious chronic hepatitis and hepatic fibrosis. (authors)

Imaging of Brain Connectivity in Dementia: Clinical Implications for Diagnosis of its Underlying Diseases

NARCIS (Netherlands)

R. Meijboom (Rozanna)

2017-01-01

markdownabstractIn this thesis we investigated the use of advanced magnetic resonance imaging (MRI) techniques in identifying subtle brain abnormalities, associating brain abnormalities with disease symptomatology, and improving early (differential) diagnosis in several diseases underlying dementia.

New trend in non-invasive prenatal diagnosis.

Science.gov (United States)

Ferrari, M; Carrera, P; Lampasona, V; Galbiati, S

2015-12-07

The presence of fetal DNA in maternal plasma represents a source of genetic material which can be obtained non-invasively. To date, the translation of noninvasive prenatal diagnosis from research into clinical practice has been rather fragmented, and despite the advances in improving the analytical sensitivity of methods, distinguishing between fetal and maternal sequences remains very challenging. Thus, the field of noninvasive prenatal diagnosis of genetic diseases has yet to attain a routine application in clinical diagnostics. On the contrary, fetal sex determination in pregnancies at high risk of sex-linked disorders, tests for fetal RHD genotyping and non-invasive assessment of chromosomal aneuploidies are now available worldwide. Copyright © 2014 Elsevier B.V. All rights reserved.

Fetal ascites and oligohydramnios: prenatal diagnosis of a sialic acid storage disease (index case).

Science.gov (United States)

Poulain, P; Odent, S; Maire, I; Milon, J; Proudhon, J F; Jouan, H; Le Marec, B

1995-09-01

In a 20-year-old primiparous patient, a routine ultrasound scan performed at 28 weeks revealed fetal ascites, bilateral talipes, and oligohydramnios. This woman, married to possibly her first cousin, was at risk for an autosomal recessive disease, a metabolic disorder. At 29 weeks, an amniotic fluid biochemical study revealed the presence of an abnormal band of free sialic acid, leading to a diagnosis of a congenital form of sialic acid storage disease. Termination of pregnancy was performed at 30 weeks. Measurement of free sialic acid in cultured fetal skin fibroblasts confirmed the diagnosis.

Imaging diagnosis of congenital heart disease with single coronary artery

International Nuclear Information System (INIS)

Zhu Ming; Li Yuhua; Zhong Yumin; Sun Aimin

2003-01-01

Objective: To report 56 cases of congenital heart disease with congenital single coronary artery and to evaluate the imaging diagnostic techniques. Methods: All 56 patients with congenital single coronary artery underwent angiocardiography. Contrast enhancement magnetic resonance angiography (CE MRA) was performed in 4 cases. 48 cases were confirmed by operation. Results: In these 56 cases, single left coronary artery was found in 44 cases and single right coronary artery was found in 12. Conclusion: Congenital heart disease with congenital single coronary artery is not rare and correct diagnosis is very important for surgery

Fat-saturated, contrast-enhanced spin echo sequences in magnetic resonance tomographic diagnosis of peritoneal carcinosis

International Nuclear Information System (INIS)

Ricke, J.; Hosten, N.; Stroszczynski, C.; Amthauer, H.; Felix, R.; Sehouli, J.; Buchmann, E.; Rieger, J.

1999-01-01

Purpose: To evaluate contrast-enhanced, fat-saturated spin echo sequences for the detection of peritoneal carcinosis with MRI. Material and Methods: 61 patients, 35 with and 26 without peritoneal carcinosis, were examined with abdominal MRI. Fat-saturated, T 1 -weighted spin echo sequences were performed before and after administration of Gd-DTPA. In addition, 22 patients with peritoneal carcinosis were examined with contrast-enhanced abdominal CT. Results: 32 of 35 patients with peritoneal carcinosis demonstrated contrast enhancement of the visceral and 30 to 35 enhancement of the parietal peritoneum (91 and 86%, respectively). Wall thickening of the intestine or parietal peritoneum were noted in 21 and 20 of 35 patients (60 and 57%, respectively), ascites in 18 of 35 patients (51%). False positive contrast enhancement of the peritoneum was noted in 4 of 26 patients (15%). In the direct comparison of MRI and CT, 22 of 22 patients versus 7 of 22 patients showed contrast enhancement of the visceral peritoneum (100 and 32%, respectively). For other signs of peritoneal carcinosis (e.g., ascites, peritoneal seedings), no differences in diagnostic reliability were demonstrated. Conclusions: The use of fat-saturated, spin echo sequences facilitates the diagnosis of peritoneal carcinosis by artifact reduction and improved detection of peritoneal contrast enhancement. MRI with fat-saturated sequences was superior to CT. (orig.) [de

Accuracy of chimeric proteins in the serological diagnosis of chronic chagas disease - a Phase II study.

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Fred Luciano Neves Santos

2017-03-01

Full Text Available The performance of current serologic tests for diagnosing chronic Chagas disease (CD is highly variable. The search for new diagnostic markers has been a constant challenge for improving accuracy and reducing the number of inconclusive results.Here, four chimeric proteins (IBMP-8.1 to -8.4 comprising immunodominant regions of different Trypanosoma cruzi antigens were tested by enzyme-linked immunosorbent assay. The proteins were used to detect specific anti-T. cruzi antibodies in the sera of 857 chagasic and 689 non-chagasic individuals to evaluate their accuracy for chronic CD diagnosis. The antigens were recombinantly expressed in Escherichia coli and purified by chromatographic methods. The sensitivity and specificity values ranged from 94.3% to 99.3% and 99.4% to 100%, respectively. The diagnostic odds ratio (DOR values were 6,462 for IBMP-8.1, 3,807 for IBMP-8.2, 32,095 for IBMP-8.3, and 283,714 for IBMP-8.4. These chimeric antigens presented DORs that were higher than the commercial test Pathozyme Chagas. The antigens IBMP-8.3 and -8.4 also showed DORs higher than the Gold ELISA Chagas test. Mixtures with equimolar concentrations were tested in order to improve the diagnosis accuracy of negative samples with high signal and positive samples with low signal. However, no gain in accuracy was observed relative to the individual antigens. A total of 1,079 additional sera were used to test cross-reactivity to unrelated diseases. The cross-reactivity rates ranged from 0.37% to 0.74% even for Leishmania spp., a pathogen showing relatively high genome sequence identity to T. cruzi. Imprecision analyses showed that IBMP chimeras are very stable and the results are highly reproducible.Our findings indicate that the IBMP-8.4 antigen can be safely used in serological tests for T. cruzi screening in blood banks and for chronic CD laboratory diagnosis.

A prospective evaluation of whole-exome sequencing as a first-tier molecular test in infants with suspected monogenic disorders.

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Stark, Zornitza; Tan, Tiong Y; Chong, Belinda; Brett, Gemma R; Yap, Patrick; Walsh, Maie; Yeung, Alison; Peters, Heidi; Mordaunt, Dylan; Cowie, Shannon; Amor, David J; Savarirayan, Ravi; McGillivray, George; Downie, Lilian; Ekert, Paul G; Theda, Christiane; James, Paul A; Yaplito-Lee, Joy; Ryan, Monique M; Leventer, Richard J; Creed, Emma; Macciocca, Ivan; Bell, Katrina M; Oshlack, Alicia; Sadedin, Simon; Georgeson, Peter; Anderson, Charlotte; Thorne, Natalie; Melbourne Genomics Health Alliance; Gaff, Clara; White, Susan M

2016-11-01

To prospectively evaluate the diagnostic and clinical utility of singleton whole-exome sequencing (WES) as a first-tier test in infants with suspected monogenic disease. Singleton WES was performed as a first-tier sequencing test in infants recruited from a single pediatric tertiary center. This occurred in parallel with standard investigations, including single- or multigene panel sequencing when clinically indicated. The diagnosis rate, clinical utility, and impact on management of singleton WES were evaluated. Of 80 enrolled infants, 46 received a molecular genetic diagnosis through singleton WES (57.5%) compared with 11 (13.75%) who underwent standard investigations in the same patient group. Clinical management changed following exome diagnosis in 15 of 46 diagnosed participants (32.6%). Twelve relatives received a genetic diagnosis following cascade testing, and 28 couples were identified as being at high risk of recurrence in future pregnancies. This prospective study provides strong evidence for increased diagnostic and clinical utility of singleton WES as a first-tier sequencing test for infants with a suspected monogenic disorder. Singleton WES outperformed standard care in terms of diagnosis rate and the benefits of a diagnosis, namely, impact on management of the child and clarification of reproductive risks for the extended family in a timely manner.Genet Med 18 11, 1090-1096.

Radiologic diagnosis of Hirschsprung's disease utilizing rectosphincteric reflex

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Nagasaki, A.; Ikeda, K.; Hayashida, Y.

1984-09-01

Artificial balloon distension of the rectum caused a reflex opening of the anal canal as seen during barium enema in 10 out of 10 normal children and in 7 of 7 children with idiopathic constipation. Reflex opening of the anal canal was not observed in any of 15 children with proven Hirschsprung's disease. This lack of response was independent of the length of aganglionosis or previous diverting colostomy and corresponded to the fact that on manometric study the intraluminal pressure of the anal canal fell in normal children but not in the children with Hirschsprung's disease. This finding greatly improves the reliability of barium enema in the diagnosis of Hirschsprung's disease.

Incidental radiologic findings at breast cancer diagnosis and likelihood of disease recurrence.

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Brothers, Joel M; Kidwell, Kelley M; Brown, Richard K J; Henry, N Lynn

2016-01-01

Despite guidelines recommending against its routine use, perioperative imaging for distant metastases is frequently performed in newly diagnosed breast cancer patients, uncovering incidental findings of uncertain significance. We assessed the clinical significance of incidental findings by determining if their presence is associated with disease recurrence. A retrospective review of staging imaging was performed in patients with stage II or III invasive breast cancer diagnosed during 2008-2009 at a large academic medical center. Data related to perioperative imaging and disease recurrence were abstracted from the medical record. Kaplan-Meier curves and Cox proportional hazards models were used to assess the association between incidental findings and time to disease recurrence. A total of 169 of 340 patients (49.7 %) underwent staging evaluation for distant metastases (CT chest, abdomen, pelvis, bone scan, and/or PET-CT). Of these, 146 (86.4 %) had at least one suspicious or indeterminate finding. Follow-up studies were performed in 73 (43.2 %) patients. Nineteen patients were diagnosed with metastatic disease at diagnosis, 18 of whom had stage III disease. In patients without metastatic disease at diagnosis, 32 later developed recurrence. Non-calcified pulmonary nodules were associated with shorter time to disease recurrence (hazard ratio 2.51, 95 % CI 1.13-5.57, p = 0.02). Imaging for distant metastases frequently reveals indeterminate findings, most of which are not associated with disease recurrence. The association between pulmonary nodules and recurrence warrants validation in an independent cohort. Overall, these findings support current guidelines recommending against routine extent of disease evaluation in patients with newly diagnosed stage II breast cancer.

The first family with Tay-Sachs disease in Cyprus: Genetic analysis reveals a nonsense (c.78G>A) and a silent (c.1305C>T) mutation and allows preimplantation genetic diagnosis.

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Georgiou, Theodoros; Christopoulos, George; Anastasiadou, Violetta; Hadjiloizou, Stavros; Cregeen, David; Jackson, Marie; Mavrikiou, Gavriella; Kleanthous, Marina; Drousiotou, Anthi

2014-12-01

Tay-Sachs disease (TSD) is a recessively inherited neurodegenerative disorder caused by mutations in the HEXA gene resulting in β-hexosaminidase A (HEX A) deficiency and neuronal accumulation of GM2 ganglioside. We describe the first patient with Tay-Sachs disease in the Cypriot population, a juvenile case which presented with developmental regression at the age of five. The diagnosis was confirmed by measurement of HEXA activity in plasma, peripheral leucocytes and fibroblasts. Sequencing the HEXA gene resulted in the identification of two previously described mutations: the nonsense mutation c.78G>A (p.Trp26X) and the silent mutation c.1305C>T (p.=). The silent mutation was reported once before in a juvenile TSD patient of West Indian origin with an unusually mild phenotype. The presence of this mutation in another juvenile TSD patient provides further evidence that it is a disease-causing mutation. Successful preimplantation genetic diagnosis (PGD) and prenatal follow-up were provided to the couple.

Thermodynamic diagnosis of diesel and biodiesel combustion processes during load-increase transient sequences

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Armas, Octavio; Ballesteros, Rosario; Cardenas, María Dolores

2012-01-01

Highlights: ► Thermodynamic diagnosis was applied to diesel combustion process during transient operation. ► Comparative analysis of thermodynamic results with different biodiesel fuels has been carried out. ► Biodiesel fuels studied have a slight effect on timing of the combustion process. ► Methodology used can be applied to improve engine control when using different alternative fuels. -- Abstract: The study of the diesel combustion process is a current topic by the need of thermal efficiency improving and the reduction of pollutant emissions. This circumstance has forced researchers and manufacturers to optimize this process not only in steady state operating conditions but also during transient operation. A zero dimensional thermodynamic diagnostic model, with three species (air, fuel evaporated and burned products), has been used to characterize the combustion process during load increase transient sequences at two different engine speed. In both sequences, three variables were studied: the valve position of the exhaust gas recirculation (EGR), the elapsed time of the transition process and the type of fuel. Three biodiesel fuels were tested pure: rapeseed, soybean and sunflower which were compared to a commercial diesel fuel used as reference. Results are presented comparing the in-cylinder average maximum pressure and temperature, and the phasing of the combustion process based on the calculation of heat release. This study has allowed the detection of the effect of the tested engine parameters and the biodiesel fuels used on the in-cylinder thermodynamic conditions during the load transient sequences studied.

Confirmatory spirometry for adults hospitalized with a diagnosis of asthma or chronic obstructive pulmonary disease exacerbation

Science.gov (United States)

2012-01-01

Background Objective measurement of airflow obstruction by spirometry is an essential part of the diagnosis of asthma or COPD. During exacerbations, the feasibility and utility of spirometry to confirm the diagnosis of asthma or chronic obstructive pulmonary disease (COPD) are unclear. Addressing these gaps in knowledge may help define the need for confirmatory testing in clinical care and quality improvement efforts. This study was designed to determine the feasibility of spirometry and to determine its utility to confirm the diagnosis in patients hospitalized with a physician diagnosis of asthma or COPD exacerbation. Methods Multi-center study of four academic healthcare institutions. Spirometry was performed in 113 adults admitted to general medicine wards with a physician diagnosis of asthma or COPD exacerbation. Two board-certified pulmonologists evaluated the spirometry tracings to determine the proportion of patients able to produce adequate quality spirometry data. Findings were interpreted to evaluate the utility of spirometry to confirm the presence of obstructive lung disease, according to the 2005 European Respiratory Society/American Thoracic Society recommendations. Results There was an almost perfect agreement for acceptability (κ = 0.92) and reproducibility (κ =0.93) of spirometry tracings. Three-quarters (73%) of the tests were interpreted by both pulmonologists as being of adequate quality. Of these adequate quality tests, 22% did not present objective evidence of obstructive lung disease. Obese patients (BMI ≥30 kg/m2) were more likely to produce spirometry tracings with no evidence of obstructive lung disease, compared to non-obese patients (33% vs. 8%, p = 0.007). Conclusions Adequate quality spirometry can be obtained in most hospitalized adults with a physician diagnosis of asthma or COPD exacerbation. Confirmatory spirometry could be a useful tool to help reduce overdiagnosis of obstructive lung disease, especially among obese