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Sample records for sequencing disease diagnosis

  1. Laser mass spectrometry for DNA sequencing, disease diagnosis, and fingerprinting

    Energy Technology Data Exchange (ETDEWEB)

    Winston Chen, C.H.; Taranenko, N.I.; Zhu, Y.F.; Chung, C.N.; Allman, S.L.

    1997-03-01

    Since laser mass spectrometry has the potential for achieving very fast DNA analysis, the authors recently applied it to DNA sequencing, DNA typing for fingerprinting, and DNA screening for disease diagnosis. Two different approaches for sequencing DNA have been successfully demonstrated. One is to sequence DNA with DNA ladders produced from Snager`s enzymatic method. The other is to do direct sequencing without DNA ladders. The need for quick DNA typing for identification purposes is critical for forensic application. The preliminary results indicate laser mass spectrometry can possibly be used for rapid DNA fingerprinting applications at a much lower cost than gel electrophoresis. Population screening for certain genetic disease can be a very efficient step to reducing medical costs through prevention. Since laser mass spectrometry can provide very fast DNA analysis, the authors applied laser mass spectrometry to disease diagnosis. Clinical samples with both base deletion and point mutation have been tested with complete success.

  2. Clinical Use of Next-Generation Sequencing in the Diagnosis of Wilson’s Disease

    Directory of Open Access Journals (Sweden)

    Dániel Németh

    2016-01-01

    Full Text Available Objective. Wilson’s disease is a disorder of copper metabolism which is fatal without treatment. The great number of disease-causing ATP7B gene mutations and the variable clinical presentation of WD may cause a real diagnostic challenge. The emergence of next-generation sequencing provides a time-saving, cost-effective method for full sequencing of the whole ATP7B gene compared to the traditional Sanger sequencing. This is the first report on the clinical use of NGS to examine ATP7B gene. Materials and Methods. We used Ion Torrent Personal Genome Machine in four heterozygous patients for the identification of the other mutations and also in two patients with no known mutation. One patient with acute on chronic liver failure was a candidate for acute liver transplantation. The results were validated by Sanger sequencing. Results. In each case, the diagnosis of Wilson’s disease was confirmed by identifying the mutations in both alleles within 48 hours. One novel mutation (p.Ala1270Ile was found beyond the eight other known ones. The rapid detection of the mutations made possible the prompt diagnosis of WD in a patient with acute liver failure. Conclusions. According to our results we found next-generation sequencing a very useful, reliable, time-saving, and cost-effective method for diagnosing Wilson’s disease in selected cases.

  3. Molecular diagnosis of glycogen storage disease and disorders with overlapping clinical symptoms by massive parallel sequencing.

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    Vega, Ana I; Medrano, Celia; Navarrete, Rosa; Desviat, Lourdes R; Merinero, Begoña; Rodríguez-Pombo, Pilar; Vitoria, Isidro; Ugarte, Magdalena; Pérez-Cerdá, Celia; Pérez, Belen

    2016-10-01

    Glycogen storage disease (GSD) is an umbrella term for a group of genetic disorders that involve the abnormal metabolism of glycogen; to date, 23 types of GSD have been identified. The nonspecific clinical presentation of GSD and the lack of specific biomarkers mean that Sanger sequencing is now widely relied on for making a diagnosis. However, this gene-by-gene sequencing technique is both laborious and costly, which is a consequence of the number of genes to be sequenced and the large size of some genes. This work reports the use of massive parallel sequencing to diagnose patients at our laboratory in Spain using either a customized gene panel (targeted exome sequencing) or the Illumina Clinical-Exome TruSight One Gene Panel (clinical exome sequencing (CES)). Sequence variants were matched against biochemical and clinical hallmarks. Pathogenic mutations were detected in 23 patients. Twenty-two mutations were recognized (mostly loss-of-function mutations), including 11 that were novel in GSD-associated genes. In addition, CES detected five patients with mutations in ALDOB, LIPA, NKX2-5, CPT2, or ANO5. Although these genes are not involved in GSD, they are associated with overlapping phenotypic characteristics such as hepatic, muscular, and cardiac dysfunction. These results show that next-generation sequencing, in combination with the detection of biochemical and clinical hallmarks, provides an accurate, high-throughput means of making genetic diagnoses of GSD and related diseases.Genet Med 18 10, 1037-1043.

  4. Next-generation sequencing for diagnosis of rare diseases in the neonatal intensive care unit

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    Daoud, Hussein; Luco, Stephanie M.; Li, Rui; Bareke, Eric; Beaulieu, Chandree; Jarinova, Olga; Carson, Nancy; Nikkel, Sarah M.; Graham, Gail E.; Richer, Julie; Armour, Christine; Bulman, Dennis E.; Chakraborty, Pranesh; Geraghty, Michael; Lines, Matthew A.; Lacaze-Masmonteil, Thierry; Majewski, Jacek; Boycott, Kym M.; Dyment, David A.

    2016-01-01

    Background: Rare diseases often present in the first days and weeks of life and may require complex management in the setting of a neonatal intensive care unit (NICU). Exhaustive consultations and traditional genetic or metabolic investigations are costly and often fail to arrive at a final diagnosis when no recognizable syndrome is suspected. For this pilot project, we assessed the feasibility of next-generation sequencing as a tool to improve the diagnosis of rare diseases in newborns in the NICU. Methods: We retrospectively identified and prospectively recruited newborns and infants admitted to the NICU of the Children’s Hospital of Eastern Ontario and the Ottawa Hospital, General Campus, who had been referred to the medical genetics or metabolics inpatient consult service and had features suggesting an underlying genetic or metabolic condition. DNA from the newborns and parents was enriched for a panel of clinically relevant genes and sequenced on a MiSeq sequencing platform (Illumina Inc.). The data were interpreted with a standard informatics pipeline and reported to care providers, who assessed the importance of genotype–phenotype correlations. Results: Of 20 newborns studied, 8 received a diagnosis on the basis of next-generation sequencing (diagnostic rate 40%). The diagnoses were renal tubular dysgenesis, SCN1A-related encephalopathy syndrome, myotubular myopathy, FTO deficiency syndrome, cranioectodermal dysplasia, congenital myasthenic syndrome, autosomal dominant intellectual disability syndrome type 7 and Denys–Drash syndrome. Interpretation: This pilot study highlighted the potential of next-generation sequencing to deliver molecular diagnoses rapidly with a high success rate. With broader use, this approach has the potential to alter health care delivery in the NICU. PMID:27241786

  5. Next-generation sequencing for diagnosis of rare diseases in the neonatal intensive care unit.

    Science.gov (United States)

    Daoud, Hussein; Luco, Stephanie M; Li, Rui; Bareke, Eric; Beaulieu, Chandree; Jarinova, Olga; Carson, Nancy; Nikkel, Sarah M; Graham, Gail E; Richer, Julie; Armour, Christine; Bulman, Dennis E; Chakraborty, Pranesh; Geraghty, Michael; Lines, Matthew A; Lacaze-Masmonteil, Thierry; Majewski, Jacek; Boycott, Kym M; Dyment, David A

    2016-08-09

    Rare diseases often present in the first days and weeks of life and may require complex management in the setting of a neonatal intensive care unit (NICU). Exhaustive consultations and traditional genetic or metabolic investigations are costly and often fail to arrive at a final diagnosis when no recognizable syndrome is suspected. For this pilot project, we assessed the feasibility of next-generation sequencing as a tool to improve the diagnosis of rare diseases in newborns in the NICU. We retrospectively identified and prospectively recruited newborns and infants admitted to the NICU of the Children's Hospital of Eastern Ontario and the Ottawa Hospital, General Campus, who had been referred to the medical genetics or metabolics inpatient consult service and had features suggesting an underlying genetic or metabolic condition. DNA from the newborns and parents was enriched for a panel of clinically relevant genes and sequenced on a MiSeq sequencing platform (Illumina Inc.). The data were interpreted with a standard informatics pipeline and reported to care providers, who assessed the importance of genotype-phenotype correlations. Of 20 newborns studied, 8 received a diagnosis on the basis of next-generation sequencing (diagnostic rate 40%). The diagnoses were renal tubular dysgenesis, SCN1A-related encephalopathy syndrome, myotubular myopathy, FTO deficiency syndrome, cranioectodermal dysplasia, congenital myasthenic syndrome, autosomal dominant intellectual disability syndrome type 7 and Denys-Drash syndrome. This pilot study highlighted the potential of next-generation sequencing to deliver molecular diagnoses rapidly with a high success rate. With broader use, this approach has the potential to alter health care delivery in the NICU. © 2016 Canadian Medical Association or its licensors.

  6. Single-shot echo-planar MR sequences in the diagnosis of intracranial infectious diseases

    International Nuclear Information System (INIS)

    Tsuchiya, Kazuhiro; Katase, Shichiro; Yoshino, Ayako; Yamakami, Norio; Hachiya, Junichi

    1998-01-01

    The purpose of this study was to present our preliminary experience in the application of echo-planar-imaging (EPI) MR sequences for the diagnosis of intracranial infectious diseases and to assess the value of these sequences. We reviewed single-shot EPI MR images obtained at 1.5 T in 17 patients and compared these images with conventional or fast spin-echo (SE) or fluid attenuated inversion-recovery (FLAIR) images. The clinical diagnoses for the 17 patients were meningitis (2 patients), encephalitis or meningoencephalitis (7 patients), brain abscess (5 patients), epidural empyema (2 patients) and Creutzfeldt-Jakob disease (1 patient). We obtained EPI-T 2 -weighted (T 2 W) images in 8 patients, EPI-FLAIR images in 13 patients and EPI-diffusion-weighted (DW) images in 14 patients. Among the 8 patients for whom EPI-T 2 W imaging was performed, EPI-T 2 W imaging yielded superior results compared with SE-T 2 W imaging in 3 patients as a consequence of patient motion and equal results compared with SE-T 2 W imaging in 5 patients. Among the 13 patients for whom EPI-FLAIR imaging was performed, the EPI-FLAIR images were superior to conventional FLAIR images in 3 unstable patients. In the remaining 10 patients for whom EPI-FLAIR imaging was performed, EPI-FLAIR images were equivalent or inferior to conventional FLAIR images. In 6 patients with encephalitis or meningoencephalitis, the encephalitic lesions showed hyperintensity in EPI-DW images to a greater extent than in images obtained with the other techniques. In 3 patients, EPI-DW images also demonstrated hyperintensity for the contents of abscesses or areas of empyema that was not seen with the other imaging techniques. The value of EPI-T 2 W and EPI-FLAIR imaging is limited in uncooperative patients. EPI-DW imaging was found to be of value for the evaluation of several intracranial infectious diseases. (author)

  7. Single-shot echo-planar MR sequences in the diagnosis of intracranial infectious diseases

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    Tsuchiya, Kazuhiro; Katase, Shichiro; Yoshino, Ayako; Yamakami, Norio; Hachiya, Junichi [Kyorin Univ., Mitaka, Tokyo (Japan). School of Medicine

    1998-06-01

    The purpose of this study was to present our preliminary experience in the application of echo-planar-imaging (EPI) MR sequences for the diagnosis of intracranial infectious diseases and to assess the value of these sequences. We reviewed single-shot EPI MR images obtained at 1.5 T in 17 patients and compared these images with conventional or fast spin-echo (SE) or fluid attenuated inversion-recovery (FLAIR) images. The clinical diagnoses for the 17 patients were meningitis (2 patients), encephalitis or meningoencephalitis (7 patients), brain abscess (5 patients), epidural empyema (2 patients) and Creutzfeldt-Jakob disease (1 patient). We obtained EPI-T{sub 2}-weighted (T{sub 2}W) images in 8 patients, EPI-FLAIR images in 13 patients and EPI-diffusion-weighted (DW) images in 14 patients. Among the 8 patients for whom EPI-T{sub 2}W imaging was performed, EPI-T{sub 2}W imaging yielded superior results compared with SE-T{sub 2}W imaging in 3 patients as a consequence of patient motion and equal results compared with SE-T{sub 2}W imaging in 5 patients. Among the 13 patients for whom EPI-FLAIR imaging was performed, the EPI-FLAIR images were superior to conventional FLAIR images in 3 unstable patients. In the remaining 10 patients for whom EPI-FLAIR imaging was performed, EPI-FLAIR images were equivalent or inferior to conventional FLAIR images. In 6 patients with encephalitis or meningoencephalitis, the encephalitic lesions showed hyperintensity in EPI-DW images to a greater extent than in images obtained with the other techniques. In 3 patients, EPI-DW images also demonstrated hyperintensity for the contents of abscesses or areas of empyema that was not seen with the other imaging techniques. The value of EPI-T{sub 2}W and EPI-FLAIR imaging is limited in uncooperative patients. EPI-DW imaging was found to be of value for the evaluation of several intracranial infectious diseases. (author)

  8. Comprehensive molecular diagnosis of Epstein-Barr virus-associated lymphoproliferative diseases using next-generation sequencing.

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    Ono, Shintaro; Nakayama, Manabu; Kanegane, Hirokazu; Hoshino, Akihiro; Shimodera, Saeko; Shibata, Hirofumi; Fujino, Hisanori; Fujino, Takahiro; Yunomae, Yuta; Okano, Tsubasa; Yamashita, Motoi; Yasumi, Takahiro; Izawa, Kazushi; Takagi, Masatoshi; Imai, Kohsuke; Zhang, Kejian; Marsh, Rebecca; Picard, Capucine; Latour, Sylvain; Ohara, Osamu; Morio, Tomohiro

    2018-05-18

    Epstein-Barr virus (EBV) is associated with several life-threatening diseases, such as lymphoproliferative disease (LPD), particularly in immunocompromised hosts. Some categories of primary immunodeficiency diseases (PIDs) including X-linked lymphoproliferative syndrome (XLP), are characterized by susceptibility and vulnerability to EBV infection. The number of genetically defined PIDs is rapidly increasing, and clinical genetic testing plays an important role in establishing a definitive diagnosis. Whole-exome sequencing is performed for diagnosing rare genetic diseases, but is both expensive and time-consuming. Low-cost, high-throughput gene analysis systems are thus necessary. We developed a comprehensive molecular diagnostic method using a two-step tailed polymerase chain reaction (PCR) and a next-generation sequencing (NGS) platform to detect mutations in 23 candidate genes responsible for XLP or XLP-like diseases. Samples from 19 patients suspected of having EBV-associated LPD were used in this comprehensive molecular diagnosis. Causative gene mutations (involving PRF1 and SH2D1A) were detected in two of the 19 patients studied. This comprehensive diagnosis method effectively detected mutations in all coding exons of 23 genes with sufficient read numbers for each amplicon. This comprehensive molecular diagnostic method using PCR and NGS provides a rapid, accurate, low-cost diagnosis for patients with XLP or XLP-like diseases.

  9. Probable Diagnosis of a Patient with Niemann-Pick Disease Type C: Managing Pitfalls of Exome Sequencing.

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    Zeiger, William A; Jamal, Nasheed I; Scheuner, Maren T; Pittman, Patricia; Raymond, Kimiyo M; Morra, Massimo; Mishra, Shri K

    2018-02-17

    Here, we present a case of a 31-year-old man with progressive cognitive decline, ataxia, and dystonia. Extensive laboratory, radiographic, and targeted genetic studies over the course of several years failed to yield a diagnosis. Initial whole exome sequencing through a commercial laboratory identified several variants of uncertain significance; however, follow-up clinical examination and testing ruled each of these out. Eventually, repeat whole exome sequencing identified a known pathogenic intronic variant in the NPC1 gene (NM_000271.4, c.1554-1009G>A) and an additional heterozygous exonic variant of uncertain significance in the NPC1 gene (NM_000271.4, c.2524T>C). Follow-up biochemical testing was consistent with a diagnosis of probable Niemann-Pick disease Type C (NP-C). This case illustrates the potential of whole exome sequencing for diagnosing rare complex neurologic diseases. It also identifies several potential common pitfalls that must be navigated by clinicians when interpreting commercial whole exome sequencing results.

  10. 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.

  11. Celiac Disease: Diagnosis.

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    Byrne, Greg; Feighery, Conleth F

    2015-01-01

    Historically the diagnosis of celiac disease has relied upon clinical, serological, and histological evidence. In recent years the use of sensitive serological methods has meant an increase in the diagnosis of celiac disease. The heterogeneous nature of the disorder presents a challenge in the study and diagnosis of the disease with patients varying from subclinical or latent disease to patients with overt symptoms. Furthermore the related gluten-sensitive disease dermatitis herpetiformis, while distinct in some respects, shares clinical and serological features with celiac disease. Here we summarize current best practice for the diagnosis of celiac disease and briefly discuss newer approaches. The advent of next-generation assays for diagnosis and newer clinical protocols may result in more sensitive screening and ultimately the possible replacement of the intestinal biopsy as the gold standard for celiac disease diagnosis.

  12. 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...

  13. [Sequencing technology in gene diagnosis and its application].

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    Yibin, Guo

    2014-11-01

    The study of gene mutation is one of the hot topics in the field of life science nowadays, and the related detection methods and diagnostic technology have been developed rapidly. Sequencing technology plays an indispensable role in the definite diagnosis and classification of genetic diseases. In this review, we summarize the research progress in sequencing technology, evaluate the advantages and disadvantages of 1(st) ~3(rd) generation of sequencing technology, and describe its application in gene diagnosis. Also we made forecasts and prospects on its development trend.

  14. 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

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

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    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

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

    Directory of Open Access Journals (Sweden)

    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

  17. 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 ...

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

    Directory of Open Access Journals (Sweden)

    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.

  19. Exome sequencing for prenatal diagnosis of fetuses with sonographic abnormalities.

    Science.gov (United States)

    Drury, Suzanne; Williams, Hywel; Trump, Natalie; Boustred, Christopher; Lench, Nicholas; Scott, Richard H; Chitty, Lyn S

    2015-10-01

    In the absence of aneuploidy or other pathogenic cytogenetic abnormality, fetuses with increased nuchal translucency (NT ≥ 3.5 mm) and/or other sonographic abnormalities have a greater incidence of genetic syndromes, but defining the underlying pathology can be challenging. Here, we investigate the value of whole exome sequencing in fetuses with sonographic abnormalities but normal microarray analysis. Whole exome sequencing was performed on DNA extracted from chorionic villi or amniocytes in 24 fetuses with unexplained ultrasound findings. In the first 14 cases sequencing was initially performed on fetal DNA only. For the remaining 10, the trio of fetus, mother and father was sequenced simultaneously. In 21% (5/24) cases, exome sequencing provided definitive diagnoses (Milroy disease, hypophosphatasia, achondrogenesis type 2, Freeman-Sheldon syndrome and Baraitser-Winter Syndrome). In a further case, a plausible diagnosis of orofaciodigital syndrome type 6 was made. In two others, a single mutation in an autosomal recessive gene was identified, but incomplete sequencing coverage precluded exclusion of the presence of a second mutation. Whole exome sequencing improves prenatal diagnosis in euploid fetuses with abnormal ultrasound scans. In order to expedite interpretation of results, trio sequencing should be employed, but interpretation can still be compromised by incomplete coverage of relevant genes. © 2015 John Wiley & Sons, Ltd.

  20. Celiac Disease Diagnosis and Management

    Science.gov (United States)

    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

  1. Classification, disease, and diagnosis.

    Science.gov (United States)

    Jutel, Annemarie

    2011-01-01

    Classification shapes medicine and guides its practice. Understanding classification must be part of the quest to better understand the social context and implications of diagnosis. Classifications are part of the human work that provides a foundation for the recognition and study of illness: deciding how the vast expanse of nature can be partitioned into meaningful chunks, stabilizing and structuring what is otherwise disordered. This article explores the aims of classification, their embodiment in medical diagnosis, and the historical traditions of medical classification. It provides a brief overview of the aims and principles of classification and their relevance to contemporary medicine. It also demonstrates how classifications operate as social framing devices that enable and disable communication, assert and refute authority, and are important items for sociological study.

  2. 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.

  3. 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.

  4. 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.

  5. Targeted next generation sequencing for molecular diagnosis of Usher syndrome.

    Science.gov (United States)

    Aparisi, María J; Aller, Elena; Fuster-García, Carla; García-García, Gema; Rodrigo, Regina; Vázquez-Manrique, Rafael P; Blanco-Kelly, Fiona; Ayuso, Carmen; Roux, Anne-Françoise; Jaijo, Teresa; Millán, José M

    2014-11-18

    Usher syndrome is an autosomal recessive disease that associates sensorineural hearing loss, retinitis pigmentosa and, in some cases, vestibular dysfunction. It is clinically and genetically heterogeneous. To date, 10 genes have been associated with the disease, making its molecular diagnosis based on Sanger sequencing, expensive and time-consuming. Consequently, the aim of the present study was to develop a molecular diagnostics method for Usher syndrome, based on targeted next generation sequencing. A custom HaloPlex panel for Illumina platforms was designed to capture all exons of the 10 known causative Usher syndrome genes (MYO7A, USH1C, CDH23, PCDH15, USH1G, CIB2, USH2A, GPR98, DFNB31 and CLRN1), the two Usher syndrome-related genes (HARS and PDZD7) and the two candidate genes VEZT and MYO15A. A cohort of 44 patients suffering from Usher syndrome was selected for this study. This cohort was divided into two groups: a test group of 11 patients with known mutations and another group of 33 patients with unknown mutations. Forty USH patients were successfully sequenced, 8 USH patients from the test group and 32 patients from the group composed of USH patients without genetic diagnosis. We were able to detect biallelic mutations in one USH gene in 22 out of 32 USH patients (68.75%) and to identify 79.7% of the expected mutated alleles. Fifty-three different mutations were detected. These mutations included 21 missense, 8 nonsense, 9 frameshifts, 9 intronic mutations and 6 large rearrangements. Targeted next generation sequencing allowed us to detect both point mutations and large rearrangements in a single experiment, minimizing the economic cost of the study, increasing the detection ratio of the genetic cause of the disease and improving the genetic diagnosis of Usher syndrome patients.

  6. 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...

  7. 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, ...

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

    Science.gov (United States)

    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.

  9. Genetic diagnosis of Mendelian disorders via RNA sequencing.

    Science.gov (United States)

    Kremer, Laura S; Bader, Daniel M; Mertes, Christian; Kopajtich, Robert; Pichler, Garwin; Iuso, Arcangela; Haack, Tobias B; Graf, Elisabeth; Schwarzmayr, Thomas; Terrile, Caterina; Koňaříková, Eliška; Repp, Birgit; Kastenmüller, Gabi; Adamski, Jerzy; Lichtner, Peter; Leonhardt, Christoph; Funalot, Benoit; Donati, Alice; Tiranti, Valeria; Lombes, Anne; Jardel, Claude; Gläser, Dieter; Taylor, Robert W; Ghezzi, Daniele; Mayr, Johannes A; Rötig, Agnes; Freisinger, Peter; Distelmaier, Felix; Strom, Tim M; Meitinger, Thomas; Gagneur, Julien; Prokisch, Holger

    2017-06-12

    Across a variety of Mendelian disorders, ∼50-75% of patients do not receive a genetic diagnosis by exome sequencing indicating disease-causing variants in non-coding regions. Although genome sequencing in principle reveals all genetic variants, their sizeable number and poorer annotation make prioritization challenging. Here, we demonstrate the power of transcriptome sequencing to molecularly diagnose 10% (5 of 48) of mitochondriopathy patients and identify candidate genes for the remainder. We find a median of one aberrantly expressed gene, five aberrant splicing events and six mono-allelically expressed rare variants in patient-derived fibroblasts and establish disease-causing roles for each kind. Private exons often arise from cryptic splice sites providing an important clue for variant prioritization. One such event is found in the complex I assembly factor TIMMDC1 establishing a novel disease-associated gene. In conclusion, our study expands the diagnostic tools for detecting non-exonic variants and provides examples of intronic loss-of-function variants with pathological relevance.

  10. [Fibrocystic breast disease--breast cancer sequence].

    Science.gov (United States)

    Habor, V; Habor, A; Copotoiu, C; Panţîru, A

    2010-01-01

    Fibrocystic breast disease has developed a major issue: the breast cancer sequence. Its involvement regarding the increse of breast cancer risk has 2 aspects: it may be either the marker of a prone tissue or a premalignant hystological deffect. Difficult differential diagnosis of benign proliferative breast lession and carcinoma led to the idea of sequency between the two: cancer does not initiate on normal mammary epithelia; it takes several proliferative stages for it to occur. In our series we analized a number of 677 breast surgical procedures where the pathologic examination reveals 115 cases (17%) of coexistence between cancer and fibrocystic breast disease. This aspect has proved to be related to earlier debut of breast cancer, suggesting that epithelial hyperplasia is a risk factor for breast cancer.

  11. 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

  12. 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

  13. 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.

  14. 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

  15. Human Genome Sequencing in Health and Disease

    Science.gov (United States)

    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

  16. 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

  17. A Genome Sequencing Program for Novel Undiagnosed Diseases

    OpenAIRE

    Bloss, Cinnamon S.; Scott-Van Zeeland, Ashley A.; Topol, Sarah E.; Darst, Burcu F.; Boeldt, Debra L.; Erikson, Galina A.; Bethel, Kelly J.; Bjork, Robert L.; Friedman, Jennifer R.; Hwynn, Nelson; Patay, Bradley A.; Pockros, Paul J.; Scott, Erick R.; Simon, Ronald A.; Williams, Gary W.

    2015-01-01

    Purpose The Scripps Idiopathic Diseases of huMan (IDIOM) study aims to discover novel gene-disease relationships and provide molecular genetic diagnosis and treatment guidance for individuals with novel diseases using genome sequencing integrated with clinical assessment and multidisciplinary case review. Methods Here we describe the IDIOM study operational protocol and initial results. Results 121 cases underwent first tier review by the principal investigators to determine if the primary in...

  18. 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.

  19. Ebola (Ebola Virus Disease): Diagnosis

    Science.gov (United States)

    ... Search Form Controls Cancel Submit Search the CDC Ebola (Ebola Virus Disease) Note: Javascript is disabled or is ... message, please visit this page: About CDC.gov . Ebola (Ebola Virus Disease) What is Ebola Virus Disease? ...

  20. Celiac Disease: Symptoms, Diagnosis & Treatment

    Science.gov (United States)

    ... Table of Contents What are some of the symptoms of celiac disease? Some people with celiac disease may not feel ... skin rash with blisters slowed growth Why are celiac disease symptoms so varied? Researchers are studying the reasons celiac ...

  1. 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

  2. The case for early use of rapid whole genome sequencing in management of critically ill infants: Late diagnosis of Coffin-Siris syndrome in an infant with left congenital diaphragmatic hernia, congenital heart disease and recurrent infections.

    Science.gov (United States)

    Sweeney, Nathaly M; Nahas, Shareef A; Chowdhury, Shimul; Del Campo, Miguel; Jones, Marilyn C; Dimmock, David P; Kingsmore, Stephen F; Investigators, Rcigm

    2018-03-16

    Congenital diaphragmatic hernia (CDH) results from incomplete formation of the diaphragm leading to herniation of abdominal organs into the thoracic cavity. CDH is associated with pulmonary hypoplasia, congenital heart disease and pulmonary hypertension. Genetically, it is associated with aneuploidies, chromosomal copy number variants, and single gene mutations. CDH is the most expensive non-cardiac congenital defect: Management frequently requires implementation of Extracorporeal Membrane Oxygenation (ECMO), which increases management expenditures 2.4 - 3.5-fold. The cost of management of CDH has been estimated to exceed $250 million per year. Despite in hospital survival of 80-90%, current management is imperfect, as a great proportion of surviving children have long-term functional deficits. We report the case of a premature infant prenatally diagnosed with CDH and congenital heart disease, who had a protracted and complicated course in the intensive care unit with multiple surgical interventions, including post-cardiac surgery ECMO, gastrostomy tube placement with Nissen fundoplication, tracheostomy for respiratory failure, recurrent infections and developmental delay. Rapid whole genome sequencing (rWGS) identified a de novo, likely pathogenic, c.3096_3100delCAAAG (p.Lys1033Argfs*32) variant in ARID1B, providing a diagnosis of Coffin-Siris syndrome. Her parents elected palliative care and she died later that day. Had rWGS been performed as a neonate, eight months of suffering and futile healthcare utilization may have been avoided. Cold Spring Harbor Laboratory Press.

  3. 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...

  4. [Molecular and prenatal diagnosis of a family with Fanconi anemia by next generation sequencing].

    Science.gov (United States)

    Gong, Zhuwen; Yu, Yongguo; Zhang, Qigang; Gu, Xuefan

    2015-04-01

    To provide prenatal diagnosis for a pregnant woman who had given birth to a child with Fanconi anemia with combined next-generation sequencing (NGS) and Sanger sequencing. For the affected child, potential mutations of the FANCA gene were analyzed with NGS. Suspected mutation was verified with Sanger sequencing. For prenatal diagnosis, genomic DNA was extracted from cultured fetal amniotic fluid cells and subjected to analysis of the same mutations. A low-frequency frameshifting mutation c.989_995del7 (p.H330LfsX2, inherited from his father) and a truncating mutation c.3971C>T (p.P1324L, inherited from his mother) have been identified in the affected child and considered to be pathogenic. The two mutations were subsequently verified by Sanger sequencing. Upon prenatal diagnosis, the fetus was found to carry two mutations. The combined next-generation sequencing and Sanger sequencing can reduce the time for diagnosis and identify subtypes of Fanconi anemia and the mutational sites, which has enabled reliable prenatal diagnosis of this disease.

  5. Presymptomatic diagnosis of Fabry's disease

    DEFF Research Database (Denmark)

    Hasselbalch, Rasmus Bo; Lav Madsen, Per; Bundgaard, Henning

    2016-01-01

    differential diagnoses in patients presenting with cardiac hypertrophy. In boys, onset has been reported in early childhood with complaints initially comprising neuropathic pain, reduced sweat production, and gastrointestinal symptoms. Later the cardiac, renal, and central nervous systems may become affected...... inheritable cardiomyopathies. The specific - precise - diagnosis may be crucial for the patient as well as the relatives....

  6. 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...

  7. A Genome Sequencing Program for Novel Undiagnosed Diseases

    Science.gov (United States)

    Bloss, Cinnamon S.; Scott-Van Zeeland, Ashley A.; Topol, Sarah E.; Darst, Burcu F.; Boeldt, Debra L.; Erikson, Galina A.; Bethel, Kelly J.; Bjork, Robert L.; Friedman, Jennifer R.; Hwynn, Nelson; Patay, Bradley A.; Pockros, Paul J.; Scott, Erick R.; Simon, Ronald A.; Williams, Gary W.; Schork, Nicholas J.; Topol, Eric J.; Torkamani, Ali

    2015-01-01

    Purpose The Scripps Idiopathic Diseases of huMan (IDIOM) study aims to discover novel gene-disease relationships and provide molecular genetic diagnosis and treatment guidance for individuals with novel diseases using genome sequencing integrated with clinical assessment and multidisciplinary case review. Methods Here we describe the IDIOM study operational protocol and initial results. Results 121 cases underwent first tier review by the principal investigators to determine if the primary inclusion criteria were satisfied, 59 (48.8%) underwent second tier review by our clinician-scientist review panel, and 17 (14.0%) patients and their family members were enrolled. 60% of cases resulted in a plausible molecular diagnosis. 18% of cases resulted in a confirmed molecular diagnosis. 2 of 3 confirmed cases led to the identification of novel gene-disease relationships. In the third confirmed case, a previously described but unrecognized disease was revealed. In all three confirmed cases, a new clinical management strategy was initiated based on the genetic findings. Conclusions Genome sequencing provides tangible clinical benefit for individuals with idiopathic genetic disease, not only in the context of molecular genetic diagnosis of known rare conditions, but also in cases where prior clinical information regarding a new genetic disorder is lacking. PMID:25790160

  8. [Application of next-generation semiconductor sequencing technologies in genetic diagnosis of inherited cardiomyopathies].

    Science.gov (United States)

    Zhao, Yue; Zhang, Hong; Xia, Xue-shan

    2015-07-01

    Inherited cardiomyopathy is the most common hereditary cardiac disease. It also causes a significant proportion of sudden cardiac deaths in young adults and athletes. So far, approximately one hundred genes have been reported to be involved in cardiomyopathies through different mechanisms. Therefore, the identification of the genetic basis and disease mechanisms of cardiomyopathies are important for establishing a clinical diagnosis and genetic testing. Next-generation semiconductor sequencing (NGSS) technology platform is a high-throughput sequencer capable of analyzing clinically derived genomes with high productivity, sensitivity and specificity. It was launched in 2010 by Life Technologies of USA, and it is based on a high density semiconductor chip, which was covered with tens of thousands of wells. NGSS has been successfully used in candidate gene mutation screening to identify hereditary disease. In this review, we summarize these genetic variations, challenge and application of NGSS in inherited cardiomyopathy, and its value in disease diagnosis, prevention and treatment.

  9. 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

  10. Heart Health - Heart Disease: Symptoms, Diagnosis, Treatment

    Science.gov (United States)

    ... 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 ...

  11. Chronic obstructive pulmonary diseasediagnosis and ...

    African Journals Online (AJOL)

    Chronic obstructive pulmonary diseasediagnosis 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 ...

  12. Preimplantation diagnosis of genetic diseases

    Directory of Open Access Journals (Sweden)

    Adiga S

    2010-01-01

    Full Text Available One of the landmarks in clinical genetics is prenatal diagnosis of genetic disorders. The recent advances in the field have made it possible to diagnose the genetic conditions in the embryos before implantation in a setting of in vitro fertilization. Polymerase chain reaction and fluorescence in situ hybridization are the two common techniques employed on a single or two cells obtained via embryo biopsy. The couple who seek in vitro fertilization may screen their embryos for aneuploidy and the couple at risk for a monogenic disorder but averse to abortion of the affected fetuses after prenatal diagnosis, are likely to be the best candidates to undergo this procedure. This article reviews the technique, indications, benefits, and limitations of pre-implantation genetic testing in clinical practice.

  13. Diagnosis of diabetic kidney disease

    DEFF Research Database (Denmark)

    Persson, Frederik; Rossing, Peter

    2018-01-01

    Approximately 20% to 40% of patients with type 1 or type 2 diabetes mellitus develop diabetic kidney disease. This is a clinical syndrome characterized by persistent albuminuria (> 300 mg/24 h, or > 300 mg/g creatinine), a relentless decline in glomerular filtration rate (GFR), raised arterial...... sign of diabetic nephropathy, the first symptom is usually peripheral edema, which occurs at a very late stage. Regular, systematic screening for diabetic kidney disease is needed in order to identify patients at risk of or with presymptomatic diabetic kidney disease. Annual monitoring of urinary...

  14. Diagnosis of spinal cord diseases

    International Nuclear Information System (INIS)

    Halimi, P.; Sigal, R.; Doyon, D.; David, P.

    1989-01-01

    Magnetic resonance imaging (MRI) nowadays plays a predominant role in the diagnosis and evaluation of spinal canal pathologies and has reduced the other exploratory methods, including computerized tomography (CT) and myelography, to an ancillary role. These pathologies are divided into three groups: those where MRI is the only imaging method (syringomyela, tumours in the spinal canal, phakomatoses, external pachimeningitis, spinal cord injuries, myelitis); those where MRI is the initial method and is completed by other examinations (vascular malformations, dysraphism, myelopathies due to cervical osteoarthritis) and those where MRI still play a lesser role than CT (degenerative lesions of the lumbar column) [fr

  15. Differential diagnosis of Jakob-Creutzfeldt disease.

    Science.gov (United States)

    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.

  16. 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

  17. Prenatal Diagnosis Of Tay-Sachs Disease

    Directory of Open Access Journals (Sweden)

    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.

  18. Premotor Diagnosis of Parkinson's Disease

    Institute of Scientific and Technical Information of China (English)

    Heinz Reichmann

    2017-01-01

    Typical Parkinsonian symptoms consist of bradykinesia plus rigidity and/or resting tremor.Some time later postural instability occurs.Pre-motor symptoms such as hyposmia,constipation,REM sleep behavior disorder and depression may antecede these motor symptoms for years.It would be ideal,if we had a biomarker which would allow to predict who with one or two of these pre-motor symptoms will develop the movement disorder Parkinson's disease (PD).Thus,it is interesting to learn that biopsies of the submandibular gland or colon biopsies may be a means to predict PD,if there is a high amout of abnormally folded alpha-synuclein and phosphorylated alpha-synuclein.This would be of relevance if we would have available means to stop the propagation of abnormal alpha-synuclein which is otherwise one of the reasons of this spreading disease PD.

  19. Neuromuscular diseases: Diagnosis and management.

    Science.gov (United States)

    Mary, P; Servais, L; Vialle, R

    2018-02-01

    Neuromuscular diseases (NMDs) affect the peripheral nervous system, which includes the motor neurons and sensory neurons; the muscle itself; or the neuromuscular junction. Thus, the term NMDs encompasses a vast array of different syndromes. Some of these syndromes are of direct relevance to paediatric orthopaedic surgeons, either because the presenting manifestation is a functional sign (e.g., toe-walking) or deformity (e.g., pes cavus or scoliosis) suggesting a need for orthopaedic attention or because orthopaedic abnormalities requiring treatment develop during the course of a known NMD. The main NMDs relevant to the orthopaedic surgeon are infantile spinal muscular atrophy (a motor neuron disease), peripheral neuropathies (chiefly, Charcot-Marie-Tooth disease), congenital muscular dystrophies, progressive muscular dystrophies, and Steinert myotonic dystrophy (or myotonic dystrophy type 1). Muscle weakness is a symptom shared by all these conditions. The paediatric orthopaedic surgeon must be familiar, not only with the musculoskeletal system, but also with many other domains (particularly respiratory and cardiac function and nutrition) that may interfere with the treatment and require preoperative management. Good knowledge of the natural history of each NMD is essential to ensure optimal timing of the therapeutic interventions, which must be performed under the best possible conditions in these usually frail patients. Timing is particularly crucial for the treatment of spinal deformities due to paraspinal muscle hypotonia during growth: depending on the disease and natural history, the treatment may involve non-operative methods or growing rods, followed by spinal fusion. A multidisciplinary approach is always required. Finally, the survival gains achieved in recent years increasingly require attention to preparing for adult life, to orthopaedic problems requiring treatment before the patient leaves the paediatric environment, and to the transition towards the

  20. Next Generation Sequencing Methods for Diagnosis of Epilepsy Syndromes

    Directory of Open Access Journals (Sweden)

    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.

  1. 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

  2. Addison's disease - the difficulty of diagnosis

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    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.

  3. Simplifying Skin Disease Diagnosis with Topical Nanotechnology.

    Science.gov (United States)

    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.

  4. Impact of exome sequencing in inflammatory bowel disease

    Science.gov (United States)

    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

  5. Early Lyme disease with spirochetemia - diagnosed by DNA sequencing

    Directory of Open Access Journals (Sweden)

    Jones William

    2010-11-01

    Full Text Available Abstract Background A sensitive and analytically specific nucleic acid amplification test (NAAT is valuable in confirming the diagnosis of early Lyme disease at the stage of spirochetemia. Findings Venous blood drawn from patients with clinical presentations of Lyme disease was tested for the standard 2-tier screen and Western Blot serology assay for Lyme disease, and also by a nested polymerase chain reaction (PCR for B. burgdorferi sensu lato 16S ribosomal DNA. The PCR amplicon was sequenced for B. burgdorferi genomic DNA validation. A total of 130 patients visiting emergency room (ER or Walk-in clinic (WALKIN, and 333 patients referred through the private physicians' offices were studied. While 5.4% of the ER/WALKIN patients showed DNA evidence of spirochetemia, none (0% of the patients referred from private physicians' offices were DNA-positive. In contrast, while 8.4% of the patients referred from private physicians' offices were positive for the 2-tier Lyme serology assay, only 1.5% of the ER/WALKIN patients were positive for this antibody test. The 2-tier serology assay missed 85.7% of the cases of early Lyme disease with spirochetemia. The latter diagnosis was confirmed by DNA sequencing. Conclusion Nested PCR followed by automated DNA sequencing is a valuable supplement to the standard 2-tier antibody assay in the diagnosis of early Lyme disease with spirochetemia. The best time to test for Lyme spirochetemia is when the patients living in the Lyme disease endemic areas develop unexplained symptoms or clinical manifestations that are consistent with Lyme disease early in the course of their illness.

  6. 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

  7. 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.

  8. Diagnosis and Updates in Celiac Disease.

    Science.gov (United States)

    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.

  9. 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

  10. 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

  11. 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.

  12. 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.

  13. 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

  14. 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.

  15. 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.

  16. 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.

  17. 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

  18. 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.

  19. 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.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  2. [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.

  3. 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)

  4. [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.

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

    Directory of Open Access Journals (Sweden)

    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.

  6. Exome Sequencing for cerebral palsies: Opening windows for differential diagnosis

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    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

  7. 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

  8. Dry eye disease: pathophysiology, classification, and diagnosis.

    Science.gov (United States)

    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.

  9. 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)

  10. Diagnosis of Charcot-Marie-Tooth Disease

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    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.

  11. 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

  12. 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.

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

    Science.gov (United States)

    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.

  14. Clinical Whole-Exome Sequencing for the Diagnosis of Mendelian Disorders

    Science.gov (United States)

    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

  15. Value of MR cisternography using three-dimensional half-fourier single-shot fast spin-echo sequences in the diagnosis of diseases related to cranial nerves VII and VIII

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    Yamakami, Norio [Kyorin Univ., Mitaka, Tokyo (Japan). School of Medicine

    1999-05-01

    The purpose of this study was to evaluate the value of MR cisternography using three-dimensional half-Fourier single-shot fast spin-echo sequences in the diagnosis of diseasea related to cranial nerves VII and VIII. With a 0.5-T imager, the most appropriate setting of echo time and section thickness was first assessed in five volunteers. This resulted in echo time of 250 msec and section thickness of 2 mm as the most effective parameters. Second, using echo time of 120 msec and section thickness of 1.5 mm that were available from the beginning of this study, the demonstration of four nerves within the audistory canal was assessed in seven volunteers. In all of the volunteers, the facial, cochlear, and vestibular nerves were determined with demonstration of each of superior and inferior vestibular nerves in four of them. Next, MR cisternography using the same echo time and section thickness was applied in 368 patients with suspicion of acoustic neurinoma and 14 with hemifacial spasm. In 28 of the 368 patients, MR cisternograms depicted an acoustic neurinoma that was confirmed on postcontrast T1-weighted images. Meanwhile, in five of the 14 patients with hemifacial spasm, MR cisternograms revealed a vessel compressing the root exit zone of the affected facial nerve. It is concluded that MR cisternography using three-dimensional half-Fourier single-shot fast spin-echo sequences can be a useful means for demonstrating nerves within the auditory nerve as well as for the screening of acoustic neurionoma. (author)

  16. Value of MR cisternography using three-dimensional half-fourier single-shot fast spin-echo sequences in the diagnosis of diseases related to cranial nerves VII and VIII

    International Nuclear Information System (INIS)

    Yamakami, Norio

    1999-01-01

    The purpose of this study was to evaluate the value of MR cisternography using three-dimensional half-Fourier single-shot fast spin-echo sequences in the diagnosis of diseasea related to cranial nerves VII and VIII. With a 0.5-T imager, the most appropriate setting of echo time and section thickness was first assessed in five volunteers. This resulted in echo time of 250 msec and section thickness of 2 mm as the most effective parameters. Second, using echo time of 120 msec and section thickness of 1.5 mm that were available from the beginning of this study, the demonstration of four nerves within the audistory canal was assessed in seven volunteers. In all of the volunteers, the facial, cochlear, and vestibular nerves were determined with demonstration of each of superior and inferior vestibular nerves in four of them. Next, MR cisternography using the same echo time and section thickness was applied in 368 patients with suspicion of acoustic neurinoma and 14 with hemifacial spasm. In 28 of the 368 patients, MR cisternograms depicted an acoustic neurinoma that was confirmed on postcontrast T1-weighted images. Meanwhile, in five of the 14 patients with hemifacial spasm, MR cisternograms revealed a vessel compressing the root exit zone of the affected facial nerve. It is concluded that MR cisternography using three-dimensional half-Fourier single-shot fast spin-echo sequences can be a useful means for demonstrating nerves within the auditory nerve as well as for the screening of acoustic neurionoma. (author)

  17. 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.

  18. 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.

  19. 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.

  20. 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

  1. Histopathology for the diagnosis of infectious diseases

    Directory of Open Access Journals (Sweden)

    Gupta E

    2009-01-01

    Full Text Available Histopathological examination of tissue biopsies for the identification of infectious organisms is a very important diagnostic tool. Conventional culture confirmation of tissue biopsies often fail to identify any pathogen as, first of all, invariably most of the tissue samples that are collected and sent for culture isolation are inappropriately collected in formalin, which prevents pathogen growth in culture media. Inadequate processing like grinding, etc. further hinders isolation. Presence of inhibitors like dead tissue debris, fibers, etc. also delays isolation. Microbiologists often lack expertise in identifying infectious pathogens directly from tissue biopsies by microscopic visualization. This review therefore acquaints microbiologists with the various methods available for detecting infectious agents by using histological stains. On histopathological examination of the tissue biopsy once, it is determined that a disease is likely to be due to an infection and has characterized the inflammatory response and hence associated microorganisms should be thoroughly looked for. Although some microorganisms or their cytopathic effects may be clearly visible on routine haematoxylin- and eosin-stained sections, additional histochemical stains are often needed for their complete characterization. Highly specific molecular techniques, such as immunohistochemistry, in situ hybridization and nucleic acid amplification, may be needed in certain instances to establish the diagnosis of infection. Through appropriate morphologic diagnoses and interlaboratory communication and collaboration, direct microscopic visualization of tissue samples can thus be very helpful in reaching a correct and rapid diagnosis.

  2. 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.

  3. Clinical and imaging diagnosis for heredodegenerative diseases.

    Science.gov (United States)

    Boddaert, Nathalie; Brunelle, Francis; Desguerre, Isabelle

    2013-01-01

    Clinical features (progressive psychomotor retardation, seizures, movement disorders and motor signs in both central and peripheral systems, sensorineural defects, and psychiatric symptoms) and brain imaging are the keys to diagnosis. CT is indicated for the detection of calcifications and blood, and for angiography. MRI in all three axes requires T1, T2, FLAIR (from 1 year on), eventually T2* or contrast administration, and diffusion in any acute condition. MR spectroscopy allows the dectection of lactate and creatine deficiency, elevated choline in high membrane turnover, and low NAA in neuronal death. The normal sequence of myelination needs to be taken into account. Pre- and neonatal anomalies include cystic and basal ganglia lesions, gyral and myelin anomalies, callosal agenesis, and large subdural spaces. Anomalies disclosed after 3 months of age include basal ganglia appearing hyper- or hypointense on T2, hypointense on T2*, or calcified white matter anomalies mainly periventricular or subcortical, or with contrast enhancement, associated with macrocephaly and/or large or very small cysts, and hypomyelination; there may be "vascular" or pseudostroke disorders, cortical atrophy, hypoplasia, or abnormal signal of the brainstem and/or cerebellum. Spectroscopy should investigate basal ganglia, white matter, and the cerebellum. MRI may reveal typical alterations of the brain at the preclinical stage in siblings of affected children. Copyright © 2013 Elsevier B.V. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    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.

  5. 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

  6. Use of Targeted Exome Sequencing for Molecular Diagnosis of Skeletal Disorders

    Science.gov (United States)

    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

  7. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  9. 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...

  10. 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 ...

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

    Directory of Open Access Journals (Sweden)

    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.

  12. 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

  13. 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

  14. Transcranial sonography for diagnosis of Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Maaser Peter

    2010-01-01

    Full Text Available Abstract Background In idiopathic Parkinson's disease (IPD transcranial sonography (TCS represents an alternative diagnostic method to verify clinical diagnosis. Although the phenomenon of an increased echogenicity of the Substantia nigra (SN is well known this method is still not widly used in the diagnostic workup. Until now reliability of this method is still a matter of debate, partly because data only existed from a few laboratories using the same ultrasound machine. Therefore our study was conducted to test the reliability of this method by using a different ultrasound device and examining a large population of control and IPD subjects by two examiners to calculate interobserver reliability. Method In this study echogenicity of SN was examined in 199 IPD patients and 201 control subjects. All individuals underwent a neurological assessment including Perdue pegboard test and Webster gait test. Using a Sonos 5500 ultrasound device area of SN was measured, echogenicity of raphe, red nuclei, thalamus, caudate and lenticular nuclei, width of third and lateral ventricle were documented. Results We found a highly characteristic enlargement of the SN echogenic signal in IPD. The cut-off value for the SN area was established using a ROC curve with a sensitivity of 95% corresponding to an area of SN of 0.2 cm2 and was found to be equivalent to the cut-off values of other studies using different ultrasound devices. Conclusions Our study shows that TCS is a reliable and highly sensitive tool for differentiation of IPD patients from individuals without CNS disorders.

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

    Science.gov (United States)

    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.

  16. 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

  17. 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.

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

    Science.gov (United States)

    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.

  19. 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

  20. 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

  1. Evaluation of time-of-flight and phase-contrast MRA sequences at 1.0 T for diagnosis of carotid artery disease. Pt. 1. A phantom and volunteer study

    International Nuclear Information System (INIS)

    Cronqvist, M.; Staahlberg, F.; Larsson, E.M.; Loenntoft, M.; Holtaas, S.

    1995-01-01

    The aim of this work was, firstly, to compare different manufacturer-provided MRA sequences in a 1.0 T MR unit, with respect to the visibility of an artificial stenosis in a flow phantom and, secondly, to evaluate the same sequences in healthy volunteers with respect to S/N ratio levels and practical in vivo implementation routines. The studied sequences were 2D and 3D TOF and sequences with an acquisition time of approximately 10 min. Quantitative signal evaluation was made using single transverse partitions in all phantom experiments. MIP angiograms and MPR reconstructions were made for visual inspection of image quality. In vivo, the images were individually evaluated by visual inspection by experienced neuroradiologists. In the evaluation of the grade and length of a stenosis, a combination of MIP and MPR was seen to be the optimal and necessary procedure. A shortening of TE played an important and significant role in the visualization of the poststenotic flow in the phantom using TOF MRA. However, the shortest TE values gave poor S/N ratio in vivo. The good results achieved in the phantom studies for 3D phase-contrast were somewhat reversed in the volunteer studies, whereas 3D TOF sequences showed good results in both the phantom and the volunteer studies. (orig.)

  2. Whole-exome sequencing for diagnosis of hereditary ichthyosis.

    Science.gov (United States)

    Sitek, J C; Kulseth, M A; Rypdal, K B; Skodje, T; Sheng, Y; Retterstøl, L

    2018-02-14

    Hereditary ichthyosis constitutes a diverse group of cornification disorders. Identification of the molecular cause facilitates optimal patient care. We wanted to estimate the diagnostic yield of applying whole-exome sequencing (WES) in the routine genetic workup of inherited ichthyosis. During a 3-year-period, all ichthyosis patients, except X-linked and mild vulgar ichthyosis, consecutively admitted to a university hospital clinic were offered WES with subsequent analysis of ichthyosis-related genes as a first-line genetic investigation. Clinical and molecular data have been collected retrospectively. Genetic variants causative for the ichthyosis were identified in 27 of 34 investigated patients (79.4%). In all, 31 causative mutations across 13 genes were disclosed, including 12 novel variants. TGM1 was the most frequently mutated gene, accounting for 43.7% of patients suffering from autosomal recessive congenital ichthyosis (ARCI). Whole-exome sequencing appears an effective tool in disclosing the molecular cause of patients with hereditary ichthyosis seen in clinical practice and should be considered a first-tier genetic test in these patients. © 2018 European Academy of Dermatology and Venereology.

  3. 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.

  4. Legionella (Legionnaires' Disease and Pontiac Fever): Diagnosis

    Science.gov (United States)

    ... Search Form Controls Cancel Submit Search The CDC Legionella (Legionnaires' Disease and Pontiac Fever) Note: Javascript is ... message, please visit this page: About CDC.gov . Legionella Home About the Disease Causes, How it Spreads, & ...

  5. MRI in diagnosis of spinal cord diseases

    International Nuclear Information System (INIS)

    Kobayashi, Naotoshi; Ono, Yuko; Kakinoki, Yoshio; Kimura, Humiko; Ebihara, Reiko; Nagayama, Takashi; Okada, Takaharu; Watanabe, Hiromi

    1985-01-01

    64 MRI studies of 57 cases of spinal cord diseases were reviewed, and following results were obtained. (1) MRI is usefull for screening method of spinal cord diseases, as CT in cerebral diseases. (2) MRI might replaces myelography in most of spinal cord disease, and more reliable informations might be obtained by MRI than in myelography in some cases, but (3) in detection of small organic changes, some technological problems are layed regarding to the image resolution of MRI. (author)

  6. Chronic obstructive pulmonary disease prognostic diagnosis ...

    African Journals Online (AJOL)

    Symptoms of COPD are characterized by chronic coughing, shortness of breadth, wheezing, sputum, cyanosis, blue lip, blue skin, blue nail and insomnia. In this paper, the traditional procedure of the medical diagnosis of COPD employed by physicians was expressed using Fuzzy classifier. The proposed expert system ...

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

    Science.gov (United States)

    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

  8. 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)

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

    Directory of Open Access Journals (Sweden)

    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.

  10. Current diagnosis and treatment of Castleman's disease.

    Science.gov (United States)

    González García, A; Moreno Cobo, M Á; Patier de la Peña, J L

    2016-04-01

    Castleman's disease is not just a single disease but rather an uncommon, heterogeneous group of nonclonal lymphoproliferative disorders, which have a broad spectrum of clinical expression. Three histological types have been reported, along with several clinical forms according to clinical presentation, histological substrate and associated diseases. Interleukin-6, its receptor polymorphisms, the human immunodeficiency virus and the human herpes virus 8 are involved in the etiopathogenesis of Castleman's disease. The study of this disease has shed light on a syndrome whose incidence is unknown. Despite recent significant advances in our understanding of this disease and the increasing therapeutic experience with rituximab, tocilizumab and siltuximab, there are still difficult questions concerning its aetiology, prognosis and optimal treatment. Copyright © 2015 Elsevier España, S.L.U. y Sociedad Española de Medicina Interna (SEMI). All rights reserved.

  11. 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.

  12. 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.

  13. 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.

  14. Diagnosis and management of vascular diseases

    International Nuclear Information System (INIS)

    Fan Xindong; Zheng Lianzhou

    2011-01-01

    Vascular disorders mainly include hemangiomas and vascular malformations, and constitute some of the most difficult diagnostic and therapeutic enigmas that can be encountered in the clinical practice. The clinical presentations are extremely variable and can range from an asymptomatic birthmark to life-threatening congestive heart failure. Attributing any of these extremely varied symptoms that a patients may present with to a vascular malformation may be a challenge to the most experienced clinical. This problem is compounded by the extreme rarity of these vascular lesions. If a clinician meets such a patient once every few years, it will be extremely difficult for the physicians to gain a steep learning curve. In such circumstances, it is difficult to formulate a standard of diagnosis and treatment for these vascular disorders. This paper aims to make a comprehensive and detailed description of the classification and diagnosis of the vascular disorders, the common used embolization agents, the concepts of interventional diagnosis and management and the therapies of various hemangiomas and vascular malformations. (authors)

  15. Alzheimer's disease: studies of diagnosis and therapy

    NARCIS (Netherlands)

    J.J. Claus (Jules Johan)

    1993-01-01

    textabstractDespite tremendous recent advances in the clinical neurology, neurobiology and epidemiology of Alzheimer's disease, the cause as well as its treatment remains as much a mystery today as when it was first described in 1907 by Alois Alzheimer.' Alzheimer's disease, the most common type

  16. 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

  17. 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.

  18. Diagnosis and management of Crohn's disease.

    Science.gov (United States)

    Wilkins, Thad; Jarvis, Kathryn; Patel, Jigneshkumar

    2011-12-15

    Crohn's disease is a chronic inflammatory condition affecting the gastrointestinal tract at any point from the mouth to the rectum. Patients may experience diarrhea, abdominal pain, fever, weight loss, abdominal masses, and anemia. Extraintestinal manifestations of Crohn's disease include osteoporosis, inflammatory arthropathies, scleritis, nephrolithiasis, cholelithiasis, and erythema nodosum. Acute phase reactants, such as C-reactive protein level and erythrocyte sedimentation rate, are often increased with inflammation and may correlate with disease activity. Levels of vitamin B12, folate, albumin, prealbumin, and vitamin D can help assess nutritional status. Colonoscopy with ileoscopy, capsule endoscopy, computed tomography enterography, and small bowel follow-through are often used to diagnose Crohn's disease. Ultrasonography, computed axial tomography, scintigraphy, and magnetic resonance imaging can assess for extraintestinal manifestations or complications (e.g., abscess, perforation). Mesalamine products are often used for the medical management of mild to moderate colonic Crohn's disease. Antibiotics (e.g., metronidazole, fluoroquinolones) are often used for treatment. Patients with moderate to severe Crohn's disease are treated with corticosteroids, azathioprine, 6-mercaptopurine, or anti-tumor necrosis factor agents (e.g., infliximab, adalimumab). Severe disease may require emergent hospitalization and a multidisciplinary approach with a family physician, gastroenterologist, and surgeon.

  19. 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...

  20. 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.

  1. 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...

  2. 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.

  3. Contested Boundaries: psychiatry, disease, and diagnosis.

    Science.gov (United States)

    Rosenberg, Charles E

    2015-01-01

    Since the 19th century, we have come to think of disease in terms of specific entities--entities defined and legitimated in terms of characteristic somatic mechanisms. Since the last third of that century, we have expanded would-be disease categories to include an ever-broader variety of emotional pain, idiosyncrasy, and culturally unsettling behaviors. Psychiatry has been the residuary legatee of these developments, developments that have always been contested at the ever-shifting boundary between disease and deviance, feeling and symptom, the random and the determined, the stigmatized and the value-free. Even in our era of reductionist hopes, psychopharmaceutical practice, and corporate strategies, the legitimacy of many putative disease categories will remain contested. The use of the specific disease entity model will always be a reductionist means to achieve necessarily holistic ends, both in terms of cultural norms and the needs of suffering individuals. Bureaucratic rigidities and stakeholder conflicts structure and intensify such boundary conflicts, as do the interests and activism of an interested lay public.

  4. In Vitro and In Vivo SERS Biosensing for Disease Diagnosis

    Directory of Open Access Journals (Sweden)

    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.

  5. Diagnosis of renal disease in rabbits.

    Science.gov (United States)

    Harcourt-Brown, Frances Margaret

    2013-01-01

    There are differences in renal anatomy and physiology between rabbits and other domestic species. Neurogenic renal ischemia occurs readily. Reversible prerenal azotemia may be seen in conjunction with gut stasis. Potentially fatal acute renal failure may be due to structural kidney damage or post-renal disease. Chronic renal failure is often associated with encephalitozoonosis. Affected rabbits cannot vomit and often eat well. Weight loss, lethargy, and cachexia are common clinical signs. Polydypsia/polyuria may be present. Derangements in calcium and phosphorus metabolism are features of renal disease. Radiography is always indicated. Urolithiasis, osteosclerosis, aortic and renal calcification are easily seen on radiographs. Copyright © 2013 Elsevier Inc. All rights reserved.

  6. 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 ...

  7. 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.

  8. Diagnosis and management of gallbladder calculus disease.

    Science.gov (United States)

    Schmidt, Malte; Dumot, John A; Søreide, Odd; Søndenaa, Karl

    2012-11-01

    The number and rate of cholecystectomy are increasing worldwide, although indications for operative treatment remain empirical, and several issues in the understanding of the condition are not concisely outlined. Our intention is to summarize and interpret current opinion regarding the indications and timing of cholecystectomy in calculous gallbladder disease. Publications concerned with gallstone disease and related topics were searched for in MEDLINE using PubMed and summarized according to clinical scenarios with an emphasis on recent research. Only one randomized controlled trial has investigated the management (conservative vs. surgery) of patients with acute cholecystitis and several have compared early with deferred surgery. Two RCTs have examined treatment of uncomplicated, symptomatic gallstone disease. Apart from these, the overwhelming majority of publications are retrospective case series. Recent literature confirms that cholecystectomy for an asymptomatic or incidental gallstone is not justified. Symptomatic, uncomplicated gallstone disease may be classified into four severity groups based on severity and frequency of pain attacks, which may guide indication for cholecystectomy. Most patients below the age of 70 seem to prefer operative treatment. Acute cholecystitis may be treated with early operation if reduction of hospital days is an issue. Patients older than 70 years with significant comorbidities may forego surgical treatment without undue hazard. Symptoms following cholecystectomy remain in 25% or more and recent evidence suggest these are caused by a functional gastrointestinal disorder.

  9. Radiographic signs and diagnosis of dental disease

    International Nuclear Information System (INIS)

    Bellows, J.

    1993-01-01

    Dental radiographs are critical for the complete assessment and treatment of dental diseases. Dental radiography is commonly used to evaluate congenital dental defects, periodontal disease, orthodontic manipulations, oral tumors, endodontic treatments, oral trauma, and any situation where an abnormality is suspected. Although standard radiographic equipment and film can be used to produce dental radiographs, dental X-ray equipment and film provide superior quality images and greater convenience of animal patient positioning. An understanding of normal dental radiographic anatomy is important when interpreting dental radiographs. Stage III periodontitis is the earliest stage of periodontal disease at which radiographic abnormalities become apparent. Bone loss associated with periodontal disease can be classified as either horizontal or vertical. Periapical radiolucencies can represent granulomas, cysts, or abscesses, whereas periapical radiodensities may represent sclerotic bone or condensing osteitis. Lytic lesions of the bone of the jaw often represent oral neoplasms. Neoplasms also can displace or disrupt teeth in the dental arch. Resorptive lesions can be external or internal and appear as radiolucent areas involving the external surface of the root or the pulp cavity, respectively. Feline dental resorptive lesions, also known as odontoclastic resorptions, are a specific form of dental resorptive lesions unique to cats

  10. Koi herpesvirus disease (khvd) surveillance and diagnosis

    DEFF Research Database (Denmark)

    Way, K.; Bergmann, S. M.; Engelsma, Marc

    together skills and experience on this fish disease from different parts of Europe. In the report of the meeting sent to the commission important issues concerning serology and cyprinid herpesvirus variants were raised. We hope that our recommendations to resolve these issues will be considered...

  11. Maple Syrup Disease: Diagnosis and Therapy

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2002-06-01

    Full Text Available Infants at high risk for maple syrup disease (MSD were identified by family history and molecular testing for the Y393N mutation of the E1a subunit of the branched chain a-ketoacid dehydrogenase in a study at Johns Hopkins University School of Medicine, Baltimore, MD.

  12. Radiopharmaceuticals for diagnosis of ischemic heart disease

    Energy Technology Data Exchange (ETDEWEB)

    Komarek, P; Chalabala, M [Institut pro Dalsi Vzdelavani Lekaru a Farmaceutu, Prague (Czechoslovakia)

    1982-01-01

    Radiopharmaceuticals used for diagnosing ischemic heart disease in the experimental and clinical practice are reviewed. The mechanism of their retention by the heart muscle is briefly described. The respective radiopharmaceuticals are divided into preparations imaging disorders in the blood supply of the cardiac muscle, diagnosing the myocardial infarction, and evaluating the contractility of the heart.

  13. 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.

  14. Differential diagnosis of granulomatous lung disease: clues and pitfalls

    Directory of Open Access Journals (Sweden)

    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.

  15. Fistulizing Crohn's disease: Diagnosis and management.

    Science.gov (United States)

    Gecse, Krisztina; Khanna, Reena; Stoker, Jaap; Jenkins, John T; Gabe, Simon; Hahnloser, Dieter; D'Haens, Geert

    2013-06-01

    Fistulizing Crohn's disease represents an evolving, yet unresolved, issue for multidisciplinary management. Perianal fistulas are the most frequent findings in fistulizing Crohn's disease. While enterocutaneous fistulas are rare, they are associated with considerable morbidity and mortality. Detailed evaluation of the fistula tract by advanced imaging techniques is required to determine the most suitable management options. The fundamentals of perianal fistula management are to evaluate the complexity of the fistula tract, and exclude proctitis and associated abscess. The main goals of the treatment are abscess drainage, which is mandatory, before initiating immunosuppressive medical therapy, resolution of fistula discharge, preservation of continence and, in the long term, avoidance of proctectomy with permanent stoma. The management of enterocutaneous fistulas comprises of sepsis control, skin care, nutritional optimization and, if needed, delayed surgery.

  16. Hyperthyroidism: diagnosis and management of Graves' disease.

    Science.gov (United States)

    Schilling, J S

    1997-06-01

    Hyperthyroidism, or thyrotoxicosis, results when the body's tissues are exposed to excessive levels of thyroid hormone. Hyperthyroidism affects 2% of women but only one-tenth as many men. Graves' disease is the most common form of hyperthyroidism, often occurring in young adults. It is an autoimmune disorder with an important genetic component. Hyperthyroidism's hallmarks include goiter and myriad signs and symptoms related to increased metabolic activity in virtually all body tissues. Increased sensitivity to circulating catecholamines adds to the clinical picture. Diagnosed by patient history, physical examination, and laboratory tests, Graves' disease is treated with antithyroid drugs, radioactive iodine, and/or surgery, plus supportive therapy. A good treatment outcome can be expected; long-term follow-up is indicated.

  17. Addison's disease - the difficulty of diagnosis

    OpenAIRE

    Preto, Clara; Correia, Joana; Pinheiro, Marina; Barroso, Fábio; Leite, Sara; Fernandes, Alexandre; Cardoso, Helena; Borges, Teresa

    2018-01-01

    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 corti...

  18. Pathogen Causing Disease of Diagnosis PCR Tecnology

    OpenAIRE

    SEVİNDİK, Emre; KIR, A. Çağrı; BAŞKEMER, Kadir; UZUN, Veysel

    2013-01-01

    Polimerase chain reaction (PCR) with which, the development of recombinant DNA tecnology, a technique commonly used in field of moleculer biology and genetic. Duplication of the target DNA is provided with this technique without the need for cloning. Some fungus species, bacteria, viruses constitutent an important group of pathogenicity in human, animals and plants. There are routinely applied types of PCR in the detection of pathogens infections diseases. These Nested- PCR, Real- Time PCR, M...

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

    Science.gov (United States)

    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.

  20. 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.

  1. Fox Den Disease: An Interesting Case Following Delayed Diagnosis.

    Science.gov (United States)

    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.

  2. ETIOLOGY, PATHOGENESIS AND CLINICAL DIAGNOSIS OF PEYRONIE’S DISEASE

    Directory of Open Access Journals (Sweden)

    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.

  3. Oncology of Reptiles: Diseases, Diagnosis, and Treatment.

    Science.gov (United States)

    Christman, Jane; Devau, Michael; Wilson-Robles, Heather; Hoppes, Sharman; Rech, Raquel; Russell, Karen E; Heatley, J Jill

    2017-01-01

    Based on necropsy review, neoplasia in reptiles has a comparable frequency to that of mammals and birds. Reptile neoplasia is now more frequently diagnosed in clinical practice based on increased use of advanced diagnostic techniques and improvements in reptilian husbandry allowing greater longevity of these species. This article reviews the current literature on neoplasia in reptiles, and focuses on advanced diagnostics and therapeutic options for reptilian patientssuffering neoplastic disease. Although most applied clinical reptile oncology is translated from dog and cat oncology, considerations specific to reptilian patients commonly encountered in clinical practice (turtles, tortoises, snakes, and lizards) are presented. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. 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.

  5. 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.

  6. 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...

  7. SYMPTOMS AND DIAGNOSIS OF HIRSCHSPRUNG’S DISEASE

    Directory of Open Access Journals (Sweden)

    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.

  8. Disease phenotype at diagnosis in pediatric Crohn's disease

    DEFF Research Database (Denmark)

    de Bie, Charlotte I; Paerregaard, Anders; Kolacek, Sanja

    2013-01-01

    It has been speculated that pediatric Crohn's disease (CD) is a distinct disease entity, with probably different disease subtypes. We therefore aimed to accurately phenotype newly diagnosed pediatric CD by using the pediatric modification of the Montreal classification, the Paris classification....

  9. 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.

  10. Association-rule-based tuberculosis disease diagnosis

    Science.gov (United States)

    Asha, T.; Natarajan, S.; Murthy, K. N. B.

    2010-02-01

    Tuberculosis (TB) is a disease caused by bacteria called Mycobacterium tuberculosis. It usually spreads through the air and attacks low immune bodies such as patients with Human Immunodeficiency Virus (HIV). This work focuses on finding close association rules, a promising technique in Data Mining, within TB data. The proposed method first normalizes of raw data from medical records which includes categorical, nominal and continuous attributes and then determines Association Rules from the normalized data with different support and confidence. Association rules are applied on a real data set containing medical records of patients with TB obtained from a state hospital. The rules determined describes close association between one symptom to another; as an example, likelihood that an occurrence of sputum is closely associated with blood cough and HIV.

  11. 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

  12. Diagnosis of Alzheimer's disease in Brazil: Supplementary exams

    Directory of Open Access Journals (Sweden)

    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.

  13. 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...

  14. 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

  15. 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

  16. Diagnosis of ischaemic heart disease with thallium-201

    Energy Technology Data Exchange (ETDEWEB)

    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.

  17. CT in diagnosis of thoracolumbar region diseases

    International Nuclear Information System (INIS)

    Dimitrov, I.; Karadjova, M.

    2003-01-01

    The lumbalgia caused by affected thoracolumbar transition (Th 11 -L 2 ) imitates the clinical symptomatic of disc lesions in the lower lumbar segments. The syndrome is presented by a pain projected in the area of the three branchings of the spinal nerves, coming from thoracolumbar segments. The aim of this study is to determine the pathological processes, causing the clinical symptoms of this syndrome, using computer tomography. 51 patients are studied with clinically proved thoracolumbar transition syndrome: 14 men and 37 women. CT slices of 96 vertebral segments are made. Two patient are scanned at Th 11 -Th 12 and L 1 -L 2 . Only Th 12 -L 1 scans are made on 10 patients and 42 are made on two neighbouring segments (41 of them on Th 11 -Th 12 and Th 12 -L 1 and one on Th 11 -L 1 and L 1 -L 2 ). An asymmetry (facet tropism) has been found at 59 levels, 21 if them are with spondiloarthrosis. Spondiloarthrosis has been found in 24 segments - 21 of them with osteochondrosis, one with disc prolapse, and 2 with disc protrusion. It is also found osteoporotic changes osteolysis in multiple myeloma, metastasis etc. During the 3 level examination no evidence for either of the mentioned changes is obtained. The CT slices of two neighbouring segments showed an unexpected change from thoracic to lumbar type of the intervertebral joints in 34 patients. The results from this study support the hypothesis about joints origin of the clinical symptoms of the thoracolumbar transition and demonstrate the importance of the computer tomography as a diagnostic method in this disease

  18. Advances in Diagnosis of Respiratory Diseases of Small Ruminants

    Directory of Open Access Journals (Sweden)

    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.

  19. [Preimplantation genetic diagnosis and monogenic inherited eye diseases].

    Science.gov (United States)

    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

  20. 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.

  1. 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)

  2. 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.

  3. 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

  4. 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

  5. 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.

  6. 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

  7. 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

  8. 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.

  9. 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.

  10. 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

  11. 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...

  12. 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

  13. 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

  14. 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

  15. Implicit sequence learning in people with Parkinson’s disease

    Directory of Open Access Journals (Sweden)

    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

  16. 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.

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

    Directory of Open Access Journals (Sweden)

    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

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

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

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    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.

  1. Decision Support System for Hepatitis Disease Diagnosis using Bayesian Network

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    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.

  2. 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

  3. ADULT-ONSET STILL'S DISEASE: DIAGNOSIS AND TREATMENT

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    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.

  4. 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.

  5. 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.

  6. Research progress in early diagnosis of Alzheimer's disease

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    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

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

    Science.gov (United States)

    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.

  8. 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.

  9. 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

  10. 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.

  11. 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)

  12. 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.

  13. 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.

  14. 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.

  15. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  18. 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)

  19. 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.

  20. Chlorophyll as a biomarker for early disease diagnosis

    Science.gov (United States)

    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.

  1. 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.

  2. 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

  3. 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.

  4. 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

  5. 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

  6. 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

  7. 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.

  8. 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.)

  9. 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

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

    Directory of Open Access Journals (Sweden)

    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.

  11. 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.

  12. 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.

  13. 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)

  14. X-ray diagnosis of complications of duodenum ulcer diseases

    International Nuclear Information System (INIS)

    Momot, N.V.

    1989-01-01

    To standardize the methods of X-ray examination, improvement and systematization of X-ray semiotics of stenosing and penetrating duodenum ulcers 157 patients are examined. X-ray examination includes traditional composition, polyprojectional examination using double contrasting with differential application of pharmaceuticals. It is shown that application of complex methods X-ray examination and adequate interpretation of examination results facilitate early diagnosis of duodenum ulcer disease complications. 8 refs.; 3 figs

  15. 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.

  16. Radionuclides in molecular technology for diagnosis of communicable diseases

    International Nuclear Information System (INIS)

    1994-05-01

    The document contains those aspects of the proceedings from a training course and a seminar organized by IAEA in 1992 which focus on molecular techniques used for the diagnosis of communicable diseases. It is divided in two parts: Part I contains 5 laboratory protocols for molecular techniques and Part II contains 9 of the 43 papers presented at the seminar which illustrates the application of molecular techniques. A separate abstract was prepared for each protocol and paper. Refs, figs and tabs

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  20. Biomarkers in the early diagnosis of Parkinson's disease

    Directory of Open Access Journals (Sweden)

    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.

  1. Specific diagnosis of brain disease with double isotope brain scanning

    Energy Technology Data Exchange (ETDEWEB)

    Ell, P J; Lotritsch, K H; Hilbrand, E; Meixner, M; Barolin, G; Scholz, H [Landesunfallkrankenhaus, Feldkirch (Austria). Dept. of Nuclear Medicine; Landesnervenkrankenhaus, Feldkirch (Austria). Dept. of Neurology)

    1976-02-01

    25 patients with known cerebral disease (either CVA's or primary or secondary tumours) diagnosed by clinical and angiographic criteria were submitted to a double siotope imaging technique using sup(99m)TcO/sub 4/- and sup(99m)Tc-EHDP. The different biological behaviour of these radiopharmaceuticals has provided specific and differential diagnosis between vascular and neoplastic disease of the brain. sup(99m)Tc-EHDP is shown to be the tracer of choice for the imaging of CVA's and sup(99m)TcO/sub 4/- is confirmed as the tracer of choice for the imaging of primary or secondary tumours in the brain.

  2. 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

  3. 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

  4. 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

  5. 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.

  6. Application of Metabonomics in Early Diagnosis of Diseases

    Directory of Open Access Journals (Sweden)

    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.

  7. Autosomal Recessive Polycystic Kidney Disease: Antenatal Diagnosis and Histopathological Correlation

    Directory of Open Access Journals (Sweden)

    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.

  8. Difficulties in diagnosis and treatment of Paget’s disease

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  10. 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

  11. Chronic kidney disease and an uncertain diagnosis of Fabry disease: Approach to a correct diagnosis

    NARCIS (Netherlands)

    van der Tol, Linda; Svarstad, Einar; Ortiz, Alberto; Tøndel, Camilla; Oliveira, João Paulo; Vogt, Liffert; Waldek, Stephen; Hughes, Derralynn A.; Lachmann, Robin H.; Terryn, Wim; Hollak, Carla E.; Florquin, Sandrine; van den Bergh Weerman, Marius A.; Wanner, Christoph; West, Michael L.; Biegstraaten, Marieke; Linthorst, Gabor E.

    2015-01-01

    Background and objectives: Screening for Fabry disease (FD), an X-linked lysosomal storage disorder, reveals a significant number of individuals with a genetic variant of unknown significance without classical FD manifestations; these variants in the a-galactosidase A gene often result in a high

  12. 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.

  13. 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.

  14. 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.

  15. An image processing technique for diagnosis of Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Massoud Mahmoudian

    2009-08-01

    Full Text Available

    • BACKGROUND: Patients with Alzheimer's disease (AD reportedly hibit hypersensitivity to much diluted tropicam solution (0.005%, a M4 muscarinic receptor antagonist. Therefore aocular application of 0.005% tropicamide ma be useful for screening dementia. The aim of this study was to simplify the pupil response test by using a new image analyzing system, which consists of a cheap, simple, and easy to use web-camera and a computer.
    • METHODS: Intraocular tropicamide of 0.005% concentration was administered in 3 groups: Alzheimer's disease patients (n = 8, average age = 76 ± 5, non-Alzheimer's disease elderly (n = 6, average age = 65 ± 7, and young subjects (n = 8, average age = 28 ± 5. Every 5 minutes for 60 minutes, image of the eye's shape were taken, and the diameter of the pupils was measured.
    • RESULTS: The results showed that differences in pupil dilation rate between Alzheimer's disease and non-Alzheimer's disease subjects were statistically significant. ROC analysis showed that after 35 minutes the sensitivity and specificity of the test were 100%.
    • CONCLUSIONS: Based on our results, we concluded that this recording system might be an appropriate and reliable tool for pupil response diagnosis test of Alzheimer's disease.
    • KEYWORDS: Alzheimer’s Disease, Tropicamide, Pupil.

  16. Pompe Disease: Early Diagnosis and Early Treatment Make a Difference

    Directory of Open Access Journals (Sweden)

    Yin-Hsiu Chien

    2013-08-01

    Full Text Available Pompe disease (glycogen storage disease type II or acid maltase deficiency is a lysosomal disorder in which acid α-glucosidase (GAA deficiencies lead to intralysosomal accumulation of glycogen in all tissues; most notably in skeletal muscles. Both the patient's age at the onset of Pompe disease symptoms and the rate of deterioration caused by the disease can vary considerably. In classical infant-onset Pompe disease (IOPD, symptoms start very early in life, and death occurs soon afterward if the disease remains untreated. In later-onset Pompe disease, symptoms are slower to appear, and patients often progress to wheelchair confinement and eventual respiratory failure. A diagnosis can be made by screening for GAA in dried blood samples, followed either by GAA assessment in lymphocytes or in fibroblasts or by the genetic analysis of mutations. Treatment by enzyme replacement therapy (ERT with alglucosidase alfa was approved for human use in 2006. In classical IOPD, treatment significantly lengthens survival and improves motor development and cardiac function. The sooner ERT begins, the better are the results. Newborn screening aims to take advantage of different technologies for diagnosing and treating newborns early on and it yields better outcomes. However, newborns diagnosed early and other long-term survivors may encounter fresh problems, making up a new phenotype of IOPD patients. Further modifications of the treatment, such as a decrease in immune responses to ERT, a higher dosage, a better uptake formulation, and gene therapy delivered locally or systemically are being explored.

  17. Implementation of Amplicon Parallel Sequencing Leads to Improvement of Diagnosis and Therapy of Lung Cancer Patients.

    Science.gov (United States)

    König, Katharina; Peifer, Martin; Fassunke, Jana; Ihle, Michaela A; Künstlinger, Helen; Heydt, Carina; Stamm, Katrin; Ueckeroth, Frank; Vollbrecht, Claudia; Bos, Marc; Gardizi, Masyar; Scheffler, Matthias; Nogova, Lucia; Leenders, Frauke; Albus, Kerstin; Meder, Lydia; Becker, Kerstin; Florin, Alexandra; Rommerscheidt-Fuss, Ursula; Altmüller, Janine; Kloth, Michael; Nürnberg, Peter; Henkel, Thomas; Bikár, Sven-Ernö; Sos, Martin L; Geese, William J; Strauss, Lewis; Ko, Yon-Dschun; Gerigk, Ulrich; Odenthal, Margarete; Zander, Thomas; Wolf, Jürgen; Merkelbach-Bruse, Sabine; Buettner, Reinhard; Heukamp, Lukas C

    2015-07-01

    The Network Genomic Medicine Lung Cancer was set up to rapidly translate scientific advances into early clinical trials of targeted therapies in lung cancer performing molecular analyses of more than 3500 patients annually. Because sequential analysis of the relevant driver mutations on fixated samples is challenging in terms of workload, tissue availability, and cost, we established multiplex parallel sequencing in routine diagnostics. The aim was to analyze all therapeutically relevant mutations in lung cancer samples in a high-throughput fashion while significantly reducing turnaround time and amount of input DNA compared with conventional dideoxy sequencing of single polymerase chain reaction amplicons. In this study, we demonstrate the feasibility of a 102 amplicon multiplex polymerase chain reaction followed by sequencing on an Illumina sequencer on formalin-fixed paraffin-embedded tissue in routine diagnostics. Analysis of a validation cohort of 180 samples showed this approach to require significantly less input material and to be more reliable, robust, and cost-effective than conventional dideoxy sequencing. Subsequently, 2657 lung cancer patients were analyzed. We observed that comprehensive biomarker testing provided novel information in addition to histological diagnosis and clinical staging. In 2657 consecutively analyzed lung cancer samples, we identified driver mutations at the expected prevalence. Furthermore we found potentially targetable DDR2 mutations at a frequency of 3% in both adenocarcinomas and squamous cell carcinomas. Overall, our data demonstrate the utility of systematic sequencing analysis in a clinical routine setting and highlight the dramatic impact of such an approach on the availability of therapeutic strategies for the targeted treatment of individual cancer patients.

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

    Directory of Open Access Journals (Sweden)

    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.

  19. 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...

  20. Diagnosis and treatment of chronic cerebrovascular disease, use of pentoxifylline

    Directory of Open Access Journals (Sweden)

    V. A. Parfenov

    2016-01-01

    Full Text Available Chronic cerebrovascular disease (CCVD is one of the most common  iagnoses in Russian neurology, by which is meant vascular cognitive impairment (VCI in modern foreign literature. There are data available in the literature on the diagnosis and treatment of CCVD (VCI. Theresults of the author’s studies show that CCVD often masks other diseases (anxiety and depressive disorders, primary headache, peripheral vestibulopathy, and Alzheimer's disease that are unfortunately poorly diagnosed in our country, so patients do not receive effective treatment. To modify risk factors for stroke (smoking and alcohol cessation, sufficient exercise, to normalize blood pressure (the use of antihypertensivemedications, to reduce blood cholesterol levels (statins, to perform antithrombotic therapy (antiplatelet agents and anticoagulants, and to use cognitive enhancers are of key importance when treating patients with CCVD (VCI. There are data on the use of pentoxifylline in patients with CCVD, vascular dementia.

  1. The role of SPECT in the diagnosis of Alzheimer's disease

    International Nuclear Information System (INIS)

    Davidson, G.P.

    1997-01-01

    Alzheimer's disease is a widespread debilitating neurological disorder which normally affects people in their later life. The personal and financial impact of this disease on patients and their families is enormous, with round-the-clock care being required for those severely affected. There is no single test available to diagnose the disease and, at this time, diagnosis is by a process of elimination. The author considers that neuroimaging has played an important role to this effect, and the use of single photon emission computed tomography (SPECT) is playing an increasing part in helping to eliminate other forms of dementia which may cause similar symptoms to Alzheimer's. It is expected that the relative availability and low cost of SPECT would make it the imaging method of choice in the future. 11 refs., tabs., figs

  2. Valvular Heart Disease in Cancer Patients: Etiology, Diagnosis, and Management.

    Science.gov (United States)

    Stewart, Merrill H; Jahangir, Eiman; Polin, Nichole M

    2017-07-01

    Cardiac valvular disease as consequence of radiation and chemotherapy during treatment for malignancy is growing in its awareness. While the overwhelming emphasis in this population has been on the monitoring and preservation of left ventricular systolic function, we are now developing a greater appreciation for the plethora of cardiac sequelae beyond this basic model. To this end many institutions across the country have developed cardio-oncology programs, which are collaborative practices between oncologists and cardiologists in order to minimize a patient's cardiovascular risk while allowing them to receive the necessary treatment for their cancer. These programs also help to recognize early nuanced treatment complications such as valvular heart disease, and provide consultation for the most appropriate course of action. In this article we will discuss the etiology, prevalence, diagnosis, and current treatment options of valvular heart disease as the result of chemotherapy and radiation.

  3. 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

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

    Science.gov (United States)

    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.

  5. Effective Diagnosis of Alzheimer's Disease by Means of Association Rules

    Science.gov (United States)

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

    In this paper we present a novel classification method of SPECT images for the early diagnosis of the Alzheimer's disease (AD). The proposed method is based on Association Rules (ARs) aiming to discover interesting associations between attributes contained in the database. The system uses firstly voxel-as-features (VAF) and Activation Estimation (AE) to find tridimensional activated brain regions of interest (ROIs) for each patient. These ROIs act as inputs to secondly mining ARs between activated blocks for controls, with a specified minimum support and minimum confidence. ARs are mined in supervised mode, using information previously extracted from the most discriminant rules for centering interest in the relevant brain areas, reducing the computational requirement of the system. Finally classification process is performed depending on the number of previously mined rules verified by each subject, yielding an up to 95.87% classification accuracy, thus outperforming recent developed methods for AD diagnosis.

  6. Statin use before diabetes diagnosis and risk of microvascular disease

    DEFF Research Database (Denmark)

    Nielsen, Sune F; Nordestgaard, Børge G

    2014-01-01

    BACKGROUND: The role of statins in the development of microvascular disease in patients with diabetes is unknown. We tested the hypothesis that statin use increases the risk of diabetic retinopathy, diabetic neuropathy, diabetic nephropathy, and gangrene of the foot in individuals with diabetes...... the cumulative incidence of diabetic retinopathy, diabetic neuropathy, diabetic nephropathy, or gangrene of the foot in statin users versus non-statin users. We analysed data with Cox regression models, adjusted for covariates including sex, age at diabetes diagnosis, and method of diabetes diagnosis. To address...... diabetic neuropathy, 1248 developed diabetic nephropathy, and 2392 developed gangrene of the foot. Compared with non-statin users, statin users had a lower cumulative incidence of diabetic retinopathy (hazard ratio 0·60, 95% CI 0·54-0·66; pdiabetic neuropathy (0·66, 0·57-0·75; p

  7. 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...

  8. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  10. 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…

  11. Is the Diagnosis of Celiac Disease Possible Without Intestinal Biopsy?

    Directory of Open Access Journals (Sweden)

    Maha Shomaf

    2017-08-01

    Full Text Available Background: Coeliac disease is defined as a state of immune-mediated hyper-responsiveness to dietary gluten from wheat, barley, or rye in genetically predisposed individuals that results in tissue damage. The diagnosis is made by microscopic examination of a small intestinal biopsy, although serological testing for antibodies against tissue transglutaminase and deamidated gliadin peptide can be of great advantage. It has been suggested that duodenal biopsy can be avoided in patients with high levels of the tissue transglutaminase antibody, since a relationship has been found to be present between tissue transglutaminase antibody titres and coeliac disease. Aims: To study the correlation between tissue transglutaminase titre and small intestinal biopsy findings in patients with coeliac disease. Study Design: Diagnostic accuracy study. Methods: Ninety-five cases of patients diagnosed with coeliac disease and with positive serum tissue transglutaminase titres were retrieved from the Jordan University Hospital archives between December 2014 and December 2015. All the cases were classified according to the Marsh classification. Results: Ninety-five cases with a positive titre for the antibody were included in this study, 73 (76.8% of them were females and 22 cases (23.2% were males. The age of the patients ranged between 4 and 75 years with a mean age ± standard deviation of 32.3±14.7. The sensitivity was the highest in Marsh IIIC and lowest in Marsh IIIA (95% versus 68% respectively. The specificity was moderate (76% for all subtypes of Marsh III. Conclusion: This study showed a positive correlation between the tissue transglutaminase titre and the degree of duodenal damage (Marsh IIIC in patients with coeliac disease. In the presence of high tissue transglutaminase levels, duodenal biopsy might not be always necessary for diagnosis, particularly in symptomatic patients

  12. Diagnosis and classification of Addison's disease (autoimmune adrenalitis).

    Science.gov (United States)

    Brandão Neto, Rodrigo Antonio; de Carvalho, Jozélio Freire

    2014-01-01

    Autoimmune adrenalitis, or autoimmune Addison disease (AAD), is the most prevalent cause of primary adrenal insufficiency in the developed world. AAD is rare and can easily be misdiagnosed as other conditions. The diagnosis depends on demonstrating inappropriately low cortisol production and the presence of high titers of adrenal cortex autoantibodies (ACAs), along with excluding other causes of adrenal failure using other tests as necessary. The treatment corticosteroid replacement, and the prognosis following the treatment is the same as the normal population. Spontaneous recovery of adrenal function has been described but is rare. Copyright © 2014 Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

    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.

  14. 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.)

  15. 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

  16. Application of forwardchaining method to diagnosis of onion plant diseases

    Science.gov (United States)

    Sitanggang, Delima; Siregar, Saut D.; Situmeang, Suryani M. F.; Indra, Evta; Sagala, Ayu R.; Sihombing, Oloan; Nababan, Marlince; Pasaribu, Hendra; Damanik, Rudolf R.; Turnip, Mardi; Saragih, Rijois I. E.

    2018-04-01

    Red Onion is a tuber plant that is widely used by the people of Indonesia, both as herbs and herbal medicines. Onion farmers have limitations in identifying diseases that attack their crops.This disease can cause crop failure against the onion.This design begins with the creation of a knowledge base up to input-output design with forward chaining method. The results of this design can assist farmers in identifying their plant diseases. Based on diagnostic results of several methods that have been done testing can diagnose diseases contained in onion plants. With symptoms data that has been determined by the expert with the value of each symptom is different. As for the symptoms that have been determined that the leaves contain patches with a value of 0.3, White leaf spots value 0.4, Leaf spots form a purple zone if it is severe 0.5, Leaf tip of 0.2, Tubers rot 0.4. Based on the above diagnostic results then get the value of diagnosis 67% forward chaining with trotol disease type, Purple spotting.

  17. 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.

  18. Preimplantation Genetic Diagnosis Counseling in Autosomal Dominant Polycystic Kidney Disease.

    Science.gov (United States)

    Murphy, Erin L; Droher, Madeline L; DiMaio, Miriam S; Dahl, Neera K

    2018-03-30

    Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common hereditary forms of chronic kidney disease. Mutations within PKD1 or PKD2 lead to innumerable fluid-filled cysts in the kidneys and in some instances, end-stage renal disease (ESRD). Affected individuals have a 50% chance of passing the mutation to each of their offspring. Assisted reproductive technology using preimplantation genetic diagnosis (PGD) allows these individuals to reduce this risk to 1% to 2%. We assess the disease burden of 8 individuals with ADPKD who have undergone genetic testing in preparation for PGD. Clinical features that predict high risk for progression to ESRD in patients with ADPKD include genotype, early onset of hypertension, a urologic event before age 35 years, and a large height-adjusted total kidney volume. Patients may have a family history of intracranial aneurysms or complications involving hepatic cysts, which may further influence the decision to pursue PGD. We also explore the cost, risks, and benefits of using PGD. All patients with ADPKD of childbearing potential, regardless of risk for progression to ESRD or risk for a significant disease burden, will likely benefit from genetic counseling. Copyright © 2018 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  19. Magnetic resonance imaging (MRI) in the diagnosis of neuromuscular diseases

    International Nuclear Information System (INIS)

    Schalke, B.C.G.; Rohkamm, R.; Kaiser, W.

    1990-01-01

    In the last few years imaging procedures became also important in the diagnosis of neuromuscular diseases. We examined more than 150 patients with different neuromuscular diseases with MRI. Conventional diagnostic procedures like EMG, muscle biopsy can not be replaced by imaging procedures. MRI gives the chance to get additional diagnostic informations. It is possible to determine exact distribution and intensity of pathological changes in the muscle. Inflammatory muscle diseases can be differrentiated by T1/T2 values from atrophic/dystrophic diseases. The resolving power is very high and allows the exact detection of affected areas even in a single muscle. This can help to reduce false negative muscle biopsies. This is very useful in children and young adults. MRI can be used for the early detection of genetic myopathies and neuropathies. MRI allows to examine all muscles, including the heart, bone artefacts are absent. Heart muscle involvement in neuromuscular diseases can directly be shown by this method without any risk for the patient. In addition P-spectroscopy can be done for better understanding of pathogenesis, especially if the exact distribution of pathological changes is known. (author)

  20. 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...

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

    International Nuclear Information System (INIS)

    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.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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 staining slides were compared with immunohistochemical (IHC) staining including: S100, NSE, CD117, CD56, Cathepsin D, Vimentin, BCL2, GFAP, Synaptophysin and chromogranin. Results: The study revealed 30 negative (absence of ganglion cells) cases (55.5%), 17 positive cases (31.04%) and seven suspected cases (12.9%) of ganglion cells on the H and E staining. On IHC staining with CD56 and Cathepsin D, all of the 17 positive cases detected through H and E, were confirmed for having ganglion cells and out of 30 cases reported negative on H and E staining, 28(93.3%) were reported negative and two (6.7%) positive by IHC staining. Of the seven suspected cases H and E staining), IHC staining detectedganglion cells only in five slides; two remained negative. Conclusions: IHC staining using CD56 and Cathepsin D improved the accuracy of diagnosis in HD when used in addition to H and E staining technique, especially for negative or suspicious slides. PMID:20671847

  4. Prenatal diagnosis of Werdnig-Hoffmann disease in China

    Institute of Scientific and Technical Information of China (English)

    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.

  5. Computed tomography in the diagnosis of pericardial heart disease

    International Nuclear Information System (INIS)

    Isner, J.M.; Carter, B.L.; Bankoff, M.S.; Konstam, M.A.; Salem, D.N.

    1982-01-01

    To evaluate the use of computed tomography (CT) in the diagnosis of pericardial heart disease, 53 patients were prospectively studied by computed tomography of the chest and cardiac ultrasound. A diagnostic-quality CT study was done for all patients; a technically satisfactory ultrasound examination was not possible in six patients. Of 47 patients in whom both chest scans and satisfactory ultrasound studies were obtained, computed tomography showed pericardial thickening not shown by ultrasound in five patients. Estimated size of pericardial effusion was the same for both computed tomography and ultrasound. Computed tomography provided quantifiable evaluation of the composition of pericardial fluid in seven patients with either hemopericardium or purulent pericarditis. Neoplastic pericardial heart disease was detected by CT scan in four of the 53 patients. Computed tomography of the chest provides a sensitive evaluation of the pericardium and quality of pericardial effusion, and is a valuable adjunct in patients in whom cardiac ultrasound is technically unsatisfactory

  6. Potential Peripheral Biomarkers for the Diagnosis of Alzheimer's Disease

    Directory of Open Access Journals (Sweden)

    Seema Patel

    2011-01-01

    Full Text Available Advances in the discovery of a peripheral biomarker for the diagnosis of Alzheimer's would provide a way to better detect the onset of this debilitating disease in a manner that is both noninvasive and universally available. This paper examines the current approaches that are being used to discover potential biomarker candidates available in the periphery. The search for a peripheral biomarker that could be utilized diagnostically has resulted in an extensive amount of studies that employ several biological approaches, including the assessment of tissues, genomics, proteomics, epigenetics, and metabolomics. Although a definitive biomarker has yet to be confirmed, advances in the understanding of the mechanisms of the disease and major susceptibility factors have been uncovered and reveal promising possibilities for the future discovery of a useful biomarker.

  7. Clinical evaluation of echography in diagnosis of thyroid disease

    International Nuclear Information System (INIS)

    Fritzsche, H.; Braendle, J.

    1983-01-01

    In 63 patients echography of thyroid was performed additionally to case history, palpation, scintigraphy and hormone tests for evaluating clinical significance of this method. The benefit of this technique is rapid measurement of thyroid size, demonstration of nodules in palpable diffuse goiters and differentiating of solid or cystic nodules of the thyroid. For diagnosis of autonomous areas in the thyroid scintigrahy remains the method of choice. Also there is no correlation of ultrasound findings and thyroid function. In routine diagnostic procedure of thyroid disease echography may replace scintigraphy only in diffuse goiter and if radionuclide imaging is not possible. Nevertheless ultrasonic evaluation of the thyroid is an important additional method in diagnostic of thyroid diseases. (Author)

  8. The diagnosis and management of cerebrovascular disease in diabetes.

    Science.gov (United States)

    Phipps, Michael S; Jastreboff, Ania M; Furie, Karen; Kernan, Walter N

    2012-06-01

    Cerebrovascular disease is a leading cause of morbidity and mortality in diabetes. Compared with nondiabetic patients, diabetic patients have at least twice the risk for stroke, earlier onset of symptoms, and worse functional outcomes. Approximately 20 % of diabetic patients will die from stroke, making it one of the leading causes of death in this population. Effective strategies for primary and secondary prevention of stroke have been developed in research cohorts that included both diabetic and nondiabetic patients. Nevertheless, prevention in diabetes has some specific considerations. In this paper, we summarize evidence to guide the diagnosis and management of stroke in diabetic patients. We propose that diabetic stroke patients should have a robust risk assessment to target interventions, like other patients with cerebrovascular disease, but with special attention to glycemic control and lifestyle modification.

  9. Overnight Dexamethasone Suppression Test in the Diagnosis of Cushing's Disease

    Directory of Open Access Journals (Sweden)

    Fatemeh Esfahanian

    2010-08-01

    Full Text Available Realizing the cause of Cushing's Syndrome (CS is one of the most challenging processes in clinical endocrinology. The long high dose dexamethasone suppression test (standard test is costly and need an extended inpatient stay. In this study we want to show the clinical utility of the overnight 8 mg dexamethasone suppression test (DST for differential diagnosis of CS in a referral center. Retrospectively from 2002-2005 we selected the patients of endocrinology ward in Imam hospital who were admitted with the diagnosis of Cushing syndrome and had 8 mg DST (modified test along with classic DST. In modified test a decrease in an 8 AM serum cortisol level of 50% or more is thought to indicate suppression and we compared the results of modified test with standard test. This test had been done on 42 patients: 10 male (23% and 32 female (76%. The mean age of patients was 31.39 (15-63, 32 with proven pituitary Cushing's disease, 7 with primary adrnal tumors and 3 with ectopic ACTH syndrome. The standard test according to 50% suppression of UFC had 90.62% sensitivity, and according to 90% suppression had 43.75% sensitivity. The sensitivity of this test was 71.85% for serum cortisol suppression. The modified test (8 mg overnight DST had 78% sensitivity. All of these tests had 100% specificity for the diagnosis of Cushing's disease. The positive predictive vale (PPV of all of these tests was 100%. The negative predictive value (NPV of modified test for the diagnosis of Cushing's disease was 58.82%. In standard test the NPV of serum cortisol was 52.6%, UFC 50% had 76.9% NPV and UFC 90% had 35.7% NPV. The results of serum cortisol suppression in modified test is better than standard test. Although 50% suppression of UFC in standard test had greater sensitivity than modified test, collecting of urine is difficult, time consuming and needing hospitalization, so we advice modified test that is much simpler and more convenient instead of standard test in the first

  10. 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.

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

    Science.gov (United States)

    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.

  12. Magnetic resonance imaging markers for early diagnosis of Parkinson's disease

    Institute of Scientific and Technical Information of China (English)

    Silvia Marino; Rosella Ciurleo; Giuseppe Di Lorenzo; Marina Barresi; Simona De Salvo; Sabrina Giacoppo; Alessia Bramanti; Pietro Lanzafame; Placido Bramanti

    2012-01-01

    Parkinson's disease (PD) is a neurodegenerative disorder characterized by selective and progressive degeneration, as well as loss of dopaminergic neurons in the substantia nigra. In PD, approximately 60-70% of nigrostriatal neurons are degenerated and 80% of content of the striatal dopamine is reduced before the diagnosis can be established according to widely accepted clinical diagnostic criteria. This condition describes a stage of disease called "prodromal", where non-motor symptoms, such as olfactory dysfunction, constipation, rapid eye movement behaviour disorder, depression, precede motor sign of PD. Detection of prodromal phase of PD is becoming an important goal for determining the prognosis and choosing a suitable treatment strategy. In this review, we present some non-invasive instrumental approaches that could be useful to identify patients in the prodromal phase of PD or in an early clinical phase, when the first motor symptoms begin to be apparent. Conventional magnetic resonance imaging (MRI) and advanced MRI techniques, such as magnetic resonance spectroscopy imaging, diffusion-weighted and diffusion tensor imaging and functional MRI, are useful to differentiate early PD with initial motor symptoms from atypical parkinsonian disorders, thus, making easier early diagnosis. Functional MRI and diffusion tensor imaging techniques can show abnormalities in the olfactory system in prodromal PD.

  13. Cognitive and behavioral changes in Huntington disease before diagnosis.

    Science.gov (United States)

    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.

  14. 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

  15. Evaluation of computed tomography in the diagnosis of liver diseases

    Energy Technology Data Exchange (ETDEWEB)

    Kato, K; Takayama, T; Katada, N; Nishimura, D; Shibata, T [Kamo Hospital, Toyota, Aichi (Japan)

    1980-10-01

    In order to evaluate computed tomography (CT) in the diagnosis of liver disease, 90 cases of diffuse parenchymal diseases and 37 cases of mass lesions were examined with a GE 8800 CT scanner. Abnormal CT findings in liver cirrhosis were characterized by splenomegaly, uneven liver margin and asites. Atrophy of right lobe and enlargement of left lobe could not be easily recognized on CT scan, compared with nuclear imaging. CT values of the liver were decreased and the ratios of CT values of the liver to those of the spleen were less than 0.9 in all cases with fatty liver. Jaundice in acute viral hepatitis can be easily differentiated from obstructive jaundice on CT scan because of observing no dilatation of intrahepatic bile duct. CT was superior in detecting space-occupying lesions to nuclear imaging and was more specific in that it was able to differentiate cystic from solid lesions. However, it was almost impossible to make a histological diagnosis of solid lesions even on CT scan.

  16. Evaluation of computed tomography in the diagnosis of liver diseases

    International Nuclear Information System (INIS)

    Kato, Katsumoto; Takayama, Tetsuo; Katada, Naoyuki; Nishimura, Daisaku; Shibata, Tokimune

    1980-01-01

    In order to evaluate computed tomography (CT) in the diagnosis of liver disease, 90 cases of diffuse parenchymal diseases and 37 cases of mass lesions were examined with GE 8800 CT scanner. Abnormal CT findings in liver cirrhosis were characterized by splenomegaly, uneven liver margin and asites. Atrophy of right lobe and enlargement of left lobe could not be easily recognized on CT scan, compared with nuclear imaging. CT values of the liver were decreased and the ratios of CT values of the liver to those of the spleen were less than 0.9 in all cases with fatty liver. Jaundice in acute viral hepatitis can be easily differentiated from obstructive jaundice on CT scan because of observing no dilatation of intrahepatic bile duct. CT was superior in detecting space-occupying lesions to nuclear imaging and was more specific in that it was able to differentiate cystic from solid lesions. However, it was almost impossible to make a histological diagnosis of solid lesions even on CT scan. (author)

  17. Intelligence system based classification approach for medical disease diagnosis

    Science.gov (United States)

    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.

  18. 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.

  19. 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.

  20. 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

  1. Accurate molecular diagnosis of phenylketonuria and tetrahydrobiopterin-deficient hyperphenylalaninemias using high-throughput targeted sequencing

    Science.gov (United States)

    Trujillano, Daniel; Perez, Belén; González, Justo; Tornador, Cristian; Navarrete, Rosa; Escaramis, Georgia; Ossowski, Stephan; Armengol, Lluís; Cornejo, Verónica; Desviat, Lourdes R; Ugarte, Magdalena; Estivill, Xavier

    2014-01-01

    Genetic diagnostics of phenylketonuria (PKU) and tetrahydrobiopterin (BH4) deficient hyperphenylalaninemia (BH4DH) rely on methods that scan for known mutations or on laborious molecular tools that use Sanger sequencing. We have implemented a novel and much more efficient strategy based on high-throughput multiplex-targeted resequencing of four genes (PAH, GCH1, PTS, and QDPR) that, when affected by loss-of-function mutations, cause PKU and BH4DH. We have validated this approach in a cohort of 95 samples with the previously known PAH, GCH1, PTS, and QDPR mutations and one control sample. Pooled barcoded DNA libraries were enriched using a custom NimbleGen SeqCap EZ Choice array and sequenced using a HiSeq2000 sequencer. The combination of several robust bioinformatics tools allowed us to detect all known pathogenic mutations (point mutations, short insertions/deletions, and large genomic rearrangements) in the 95 samples, without detecting spurious calls in these genes in the control sample. We then used the same capture assay in a discovery cohort of 11 uncharacterized HPA patients using a MiSeq sequencer. In addition, we report the precise characterization of the breakpoints of four genomic rearrangements in PAH, including a novel deletion of 899 bp in intron 3. Our study is a proof-of-principle that high-throughput-targeted resequencing is ready to substitute classical molecular methods to perform differential genetic diagnosis of hyperphenylalaninemias, allowing the establishment of specifically tailored treatments a few days after birth. PMID:23942198

  2. The value of MR imaging of PDFASAT sequence in the diagnosis of extremities occult fractures

    International Nuclear Information System (INIS)

    Lu Lingquan; Xu Mingshen; Wu Qianzhi; Mao Chunnan; Wang Shuzi; Zhou Xingfan; Wang Liping

    2004-01-01

    Objective: To investigate the value of MR imaging of proton density weighted-fat saturated (PDFASAT) sequence in detecting the occult fracture of extremities. Methods: Thirty-one patients with acute trauma were studied using radiography and MR imaging within 45 days. MR sequences included FSE T 1 WI, T 2 WI, and PDFASAT. 21 occult fractures occurred in the knee joint, 6 in the hip joint, 1 in the elbow joint, 2 in the shoulder, and 1 in the ankle. Results: All 31 cases had normal radiographic results. 10 cases with proximal fibula, 4 with proximal tibia and 7 with femur condyle occult fractures were found in 21 knee joint acute trauma cases. 2 cases with intertrochanteric, 2 with femoral neck and 2 with cotyle occult fractures were found in 6 hip joint trauma cases. 2 proximal humerus occult fractures were found in 2 shoulder cases. 1 distal humerus and 1 distal fibula occult fracture was found in elbow and ankle cases. MR imaging demonstrated irregular linear low signal in the subcortical region on both T 1 WI and T 2 WI, and high signal changes around low signal were seen on T 2 WI in some cases. The high signal in PDFASAT sequence was more remarkable and wider than that on both T 1 WI and T 2 WI. Conclusion: MR imaging could determine the diagnosis of acute and chronic occult fractures. MRI should be the next choice when plain films fail to reveal suspected fractures in setting of suggestive symptoms and positive physical examination. PDFASAT would be the best effective sequence among the T 1 WI, T 2 WI, and PDFASAT. (author)

  3. Diagnosis and management of right colonic diverticular disease: A review.

    Science.gov (United States)

    Ferrara, Francesco; Bollo, Jesús; Vanni, Letizia V; Targarona, Eduardo M

    2016-12-01

    The aim of this narrative review is to define the clinical-pathological characteristics and to clarify the management of right colonic diverticular disease. It is rare in Europe, USA and Australia and more common in Asia. In the recent years its incidence has increased in the West, with various distributions among populations. Many studies have reported that it is difficult to differentiate the presenting symptoms of this disease from those of appendicitis before surgery, because the signs and symptoms are similar, so misdiagnosis is not infrequent. With accurate imaging studies it is possible to reach a precise preoperative diagnosis, in order to assess an accurate treatment strategy. Currently the management of this disease is not well defined, no clear guidelines have been proposed and it is not known whether the guidelines for left colonic diverticular disease can also be applied for it. Several authors have stated that conservative management is the best approach, even in case of recurrence, and surgery should be indicated in selected cases. Copyright © 2016. Publicado por Elsevier España, S.L.U.

  4. Noninvasive diagnosis of allograft vascular disease after heart transplantation

    Directory of Open Access Journals (Sweden)

    Fernando Bacal

    2001-01-01

    Full Text Available OBJECTIVE: To determine the predictive values of noninvasive tests for the detection of allograft vascular disease. METHODS: We studied 39 patients with mean ages of 48±13 years and a follow-up period of 86±13 months. The diagnosis of allograft vascular disease was made by cine-coronary arteriography, and it was considered as positive if lesions existed that caused > or = 50% obstruction of the lumen. Patients underwent 24h Holter monitoring, thallium scintigraphy, a treadmill stress test, and dobutamine stress echocardiography. Sensitivity, specificity, and positive and negative predictive values were determined in percentages for each method, as compared with the cine-coronary arteriography results. RESULTS: Allograft vascular disease was found in 15 (38% patients. The Holter test showed 15.4% sensitivity, 95.5% specificity. For the treadmill stress test, sensitivity was 10%, specificity was 100%. When thallium scintigraphy was used, sensitivity was 40%, specificity 95.8%. On echocardiography with dobutamine, we found a 63.6% sensitivity, 91.3% specificity. When the dobutamine echocardiogram was associated with scintigraphy, sensitivity was 71.4%, specificity was 87%. CONCLUSION: In this group of patients, the combination of two noninvasive methods (dobutamine echocardiography and thallium scintigraphy may be a good alternative for the detection of allograft vascular disease in asymptomatic patients with normal ventricular function.

  5. Impaired visuospatial transformation but intact sequence processing in Parkinson disease.

    Science.gov (United States)

    Leek, E Charles; Kerai, Julie H; Johnston, Stephen J; Hindle, John V; Bracewell, R Martyn

    2014-09-01

    We examined whether visuospatial deficits in Parkinson disease (PD) can be explained by a domain-general, nonspatial impairment in the sequencing or serial chaining of mental operations. PD has been shown to be associated with impaired visuospatial processing, but the mechanisms of this impairment remain unclear. Thirteen patients with PD and 20 age-matched, neurologically normal controls performed a visuospatial grid navigation task requiring sequential spatial transformations. The participants also performed a control task of serial number subtraction designed to assess their nonvisuospatial sequencing. The tasks were matched in structure and difficulty. The patients were impaired on the visuospatial task but not in serial number subtraction. This finding suggests that visuospatial processing impairments in PD do not derive from a general impairment affecting sequencing or serial chaining. We argue that visuospatial deficits in PD result from impairments to spatial transformation routines involved in the computation of mappings between spatial locations. These routines are mediated by dopaminergic pathways linking the basal ganglia, prefrontal cortex, supplementary motor area, and parietal cortex.

  6. 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)

  7. Diagnosis and epidemiology of animal diseases in Latin America

    International Nuclear Information System (INIS)

    Cooling, A.

    1998-01-01

    Support for scientists and their endeavours in developing countries by the Joint FAO/IAEA Division of Nuclear Techniques in Food and Agriculture is provided through FAO/IAEA Co-ordinated Research Projects (CRP) and IAEA Technical Co-operation Projects (TCPs). Using these mechanisms the Animal Production and Health Section of the Joint FAO/IAEA Division of Nuclear Techniques in Food and Agricultural aims to encourage and improve the capacity of national institutions in developing countries to identify and resolve problems connected with improving livestock productivity and health. In 1986, the Section introduced and animal health component into its Project. The initial support was for five years but in 1991 this was extended for a further three years and linked with the support available from the IAEA's Technical Co-operation Project through national and regional TCPs and ARCAL activities in Latin America dealing with diagnosis of animal diseases. Central to this overall project ws the use of ELISA for the diagnosis and control of livestock diseases. FAO/IAEA CRPs are developed around a well defined research topic on which between 15 and 20 national institutes collaborate - the topic itself being defined through consultation with national authorities in developing and developed countries and international agricultural research centers and organizations. The primary role of the Joint FAO/IAEA Division of Nuclear Techniques in Food and Agriculture in such programmes is to ensure that the inputs and efforts under these programmes are co-ordinated and that the results are published. The studies being reported in this IAEA TECDOC were initiated in 1991 and whilst the focus was on three major disease affecting livestock in the region (foot-and-mouth disease (FMD), brucellosis and babesiosis) the approach taken by individual Research Control holders was different and thus in some cases research concentrated on assay validation whilst in other cases the focus was on the

  8. 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.

  9. Diagnosis of dry eye disease and emerging technologies

    Science.gov (United States)

    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

  10. Magnetic resonance imaging in the diagnosis of pancreatic diseases

    International Nuclear Information System (INIS)

    Yamaguchi, Taketo; Ebara, Masaaki; Saisho, Hiromitsu

    1987-01-01

    Fifty patients with various pancreatic diseases and 22 without pancreatic disease were studied by a magnetic resonance imaging (MRI) to compare its diagnostic capability with that by an X-ray CT scan. To differentiate pancreas clearly from the bowel, an iron solution was orally administered as contrast medium, resulting in a usefullness, especially to differentiate the head of the pancreas from the bowel. The head of the pancreas could be identified in 89 % after iron solution but only in 62 % without it. MRI was inferior to CT in terms of visualization of the pancreatic duct and pancreatic stones, but was superior in a visualization of vessels around the pancreas. MRI was considered to be useful for a detection of carcinoma infiltrating to vessels. Pancreatic carcinoma was differentiated from chronic pancreatitis in terms of a local enlargement and disappearance of fat around the pancreas shown on MRI findings. The present results also showed statistically significant differences in T 1 relaxation times among normal pancreas, chronic pancreatitis and pancreatic carcinoma, suggesting a useful marker in the differential diagnosis of pancreatic diseases. (author)

  11. Technology needs for tomorrow's treatment and diagnosis of macular diseases

    Science.gov (United States)

    Soubrane, Gisèle

    2008-02-01

    Retinal imaging is the basis of macular disease's diagnosis. Currently available technologies in clinical practice are fluorescein and indocyanin green (ICG) angiographies, in addition to optical coherence tomography (OCT), which is an in vivo "histology-like" cross-sectional images of the retina. Recent developments in the field of OCT imaging include Spectral-Domain OCT. However OCT remains a static view of the macula with no direct link with dynamic observation obtained by angiographies. Adaptative optics is an encouraging perspective for fundus analysis in the future, and could be linked to OCT or angiographies. Treatments of macular disease have exploded these past few years. Pharmacologic inhibition of angiogenesis represents a novel approach in the treatment of choroidal neovascularization in eyes with age-related macular degeneration. The major action explored is the direct inhibition of the protein VEGF with antibody-like products. New anti-VEGF drugs are in development aiming at the VEGF receptors or synthesis of VEGF. But various components of the neovascular cascade, including growth factor expression, extracellular matrix modulation, integrin inhibition represent potential targets for modulation with drugs. Intra-vitreal injections are nowadays the main route of administration for these new treatments but they are potentially responsible of side effects such as endophtalmitis. Development of other routes of treatment would require new formulation of used drugs. The improvement of retinal imaging leads to a better understanding of macular disease mechanisms and will help to develop new routes and targets of treatment.

  12. Application of Whole Exome Sequencing in Six Families with an Initial Diagnosis of Autosomal Dominant Retinitis Pigmentosa: Lessons Learned

    Science.gov (United States)

    Fernandez-San Jose, Patricia; Liu, Yichuan; March, Michael; Pellegrino, Renata; Golhar, Ryan; Corton, Marta; Blanco-Kelly, Fiona; López-Molina, Maria Isabel; García-Sandoval, Blanca; Guo, Yiran; Tian, Lifeng; Liu, Xuanzhu; Guan, Liping; Zhang, Jianguo; Keating, Brendan; Xu, Xun

    2015-01-01

    This study aimed to identify the genetics underlying dominant forms of inherited retinal dystrophies using whole exome sequencing (WES) in six families extensively screened for known mutations or genes. Thirty-eight individuals were subjected to WES. Causative variants were searched among single nucleotide variants (SNVs) and insertion/deletion variants (indels) and whenever no potential candidate emerged, copy number variant (CNV) analysis was performed. Variants or regions harboring a candidate variant were prioritized and segregation of the variant with the disease was further assessed using Sanger sequencing in case of SNVs and indels, and quantitative PCR (qPCR) for CNVs. SNV and indel analysis led to the identification of a previously reported mutation in PRPH2. Two additional mutations linked to different forms of retinal dystrophies were identified in two families: a known frameshift deletion in RPGR, a gene responsible for X-linked retinitis pigmentosa and p.Ser163Arg in C1QTNF5 associated with Late-Onset Retinal Degeneration. A novel heterozygous deletion spanning the entire region of PRPF31 was also identified in the affected members of a fourth family, which was confirmed with qPCR. This study allowed the identification of the genetic cause of the retinal dystrophy and the establishment of a correct diagnosis in four families, including a large heterozygous deletion in PRPF31, typically considered one of the pitfalls of this method. Since all findings in this study are restricted to known genes, we propose that targeted sequencing using gene-panel is an optimal first approach for the genetic screening and that once known genetic causes are ruled out, WES might be used to uncover new genes involved in inherited retinal dystrophies. PMID:26197217

  13. Diagnosis and classification of celiac disease and gluten sensitivity.

    Science.gov (United States)

    Tonutti, Elio; Bizzaro, Nicola

    2014-01-01

    Celiac disease is a complex disorder, the development of which is controlled by a combination of genetic (HLA alleles) and environmental (gluten ingestion) factors. New diagnostic guidelines developed by ESPGHAN emphasize the crucial role of serological tests in the diagnostic process of symptomatic subjects, and of the detection of HLA DQ2/DQ8 alleles in defining a diagnosis in asymptomatic subjects belonging to at-risk groups. The serological diagnosis of CD is based on the detection of class IgA anti-tissue transglutaminase (anti-tTG) and anti-endomysial antibodies. In patients with IgA deficiency, anti-tTG or anti-deamidated gliadin peptide antibody assays of the IgG class are used. When anti-tTG antibody levels are very high, antibody specificity is absolute and CD can be diagnosed without performing a duodenum biopsy. Non-celiac gluten sensitivity is a gluten reaction in which both allergic and autoimmune mechanisms have been ruled out. Diagnostic criteria include the presence of symptoms similar to those of celiac or allergic patients; negative allergological tests and absence of anti-tTG and EMA antibodies; normal duodenal histology; evidence of disappearance of the symptoms with a gluten-free diet; relapse of the symptoms when gluten is reintroduced. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. Peripheral neuropathy in complex inherited diseases: an approach to diagnosis.

    Science.gov (United States)

    Rossor, Alexander M; Carr, Aisling S; Devine, Helen; Chandrashekar, Hoskote; Pelayo-Negro, Ana Lara; Pareyson, Davide; Shy, Michael E; Scherer, Steven S; Reilly, Mary M

    2017-10-01

    Peripheral neuropathy is a common finding in patients with complex inherited neurological diseases and may be subclinical or a major component of the phenotype. This review aims to provide a clinical approach to the diagnosis of this complex group of patients by addressing key questions including the predominant neurological syndrome associated with the neuropathy, for example, spasticity, the type of neuropathy and the other neurological and non-neurological features of the syndrome. Priority is given to the diagnosis of treatable conditions. Using this approach, we associated neuropathy with one of three major syndromic categories: (1) ataxia, (2) spasticity and (3) global neurodevelopmental impairment. Syndromes that do not fall easily into one of these three categories can be grouped according to the predominant system involved in addition to the neuropathy, for example, cardiomyopathy and neuropathy. We also include a separate category of complex inherited relapsing neuropathy syndromes, some of which may mimic Guillain-Barré syndrome, as many will have a metabolic aetiology and be potentially treatable. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  15. 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.

  16. The radiological diagnosis of thoracolumbar disc disease in the Dachshund

    International Nuclear Information System (INIS)

    Kirberger, R.M.; Roos, C.J.; Lubbe, A.M.

    1992-01-01

    The accuracy of survey radiographs in the diagnosis of acute thoracolumbar disc disease in 36 Dachshunds was determined by comparison with lumbar myelographic findings using iohexol. The value of making radiographs immediately after injection of contrast medium and the effectiveness of oblique radiographs in determining the exact circumferential distribution of extruding or protruding disc material were assessed. The presence of a double contrast medium column, resistance to injection and the presence of cerebrospinal fluid flow during needle placement was also evaluated. The location of the affected disc was accurately determined on survey radiographs in only 26 dogs. The myelographic technique used in this study resulted in the correct intervertebral space being identified, together with the exact circumferential distribution of disc material, in 35 dogs. Survey radiographs alone are inadequate for localization of protruding or extruding disc material

  17. Jane Austen and Addison's disease: an unconvincing diagnosis.

    Science.gov (United States)

    White, K G

    2009-12-01

    Jane Austen's letters describe a two-year deterioration into bed-ridden exhaustion, with unusual colouring, bilious attacks and rheumatic pains. In 1964, Zachary Cope postulated tubercular Addison's to explain her symptoms and her relatively pain-free illness. Literary scholars later countered this posthumous diagnosis on grounds that are not well substantiated, while medical authors supported his conclusion. Important symptoms reported by contemporary Addison's patients-mental confusion, generalised pain and suffering, weight loss and anorexia-are absent from Jane Austen's letters. Thus, by listening to the patient's perspective, we can conclude it is unlikely that Addison's disease caused Jane Austen's demise. Disseminated bovine tuberculosis would offer a coherent explanation for her symptoms, so that Cope's original suggestion of infective tuberculosis as the cause of her illness may have been correct.

  18. Delayed diagnosis of Addison's disease: an approach to management.

    Science.gov (United States)

    Mascarenhas, Janice V; Jude, Edward B

    2014-07-18

    Addison's disease accounts for the majority of cases of adrenal failure that are detected during hospital admissions. Unfortunately, prompt diagnosis of this condition is often delayed due to varied atypical manifestations and inadequate assessment at the time of presentation. We report a case of a 52-year-old woman who was detected to have hypotension during routine colonoscopy for evaluation of anaemia and progressive weight loss. During admission for evaluation of hypotension, she was also detected to have hyponatremia. Hyponatremia and hypotension failed to improve despite fluid resuscitation. Our endocrinological opinion was sought for and on further evaluation she was diagnosed with primary adrenal insufficiency. Glucocorticoid and mineralocorticoid replacement therapy were eventually instituted, which was followed by restoration of blood pressure and normalisation of serum sodium levels. 2014 BMJ Publishing Group Ltd.

  19. Progress in the molecular diagnosis of Lyme disease.

    Science.gov (United States)

    Ružić-Sabljić, Eva; Cerar, Tjaša

    2017-01-01

    Current laboratory testing of Lyme borreliosis mostly relies on serological methods with known limitations. Diagnostic modalities enabling direct detection of pathogen at the onset of the clinical signs could overcome some of the limitations. Molecular methods detecting borrelial DNA seem to be the ideal solution, although there are some aspects that need to be considered. Areas covered: This review represent summary and discussion of the published data obtained from literature searches from PubMed and The National Library of Medicine (USA) together with our own experience on molecular diagnosis of Lyme disease. Expert commentary: Molecular methods are promising and currently serve as supporting diagnostic testing in Lyme borreliosis. Since the field of molecular diagnostics is under rapid development, molecular testing could become an important diagnostic modality.

  20. Diagnosis of Iron-Deficiency Anemia in Chronic Kidney Disease.

    Science.gov (United States)

    Bahrainwala, Jehan; Berns, Jeffrey S

    2016-03-01

    Anemia is a common and clinically important consequence of chronic kidney disease (CKD). It is most commonly a result of decreased erythropoietin production by the kidneys and/or iron deficiency. Deciding on the appropriate treatment for anemia associated with CKD with iron replacement and erythropoietic-stimulating agents requires an ability to accurately diagnose iron-deficiency anemia. However, the diagnosis of iron-deficiency anemia in CKD patients is complicated by the relatively poor predictive ability of easily obtained routine serum iron indices (eg, ferritin and transferrin saturation) and more invasive gold standard measures of iron deficiency (eg, bone marrow iron stores) or erythropoietic response to supplemental iron. In this review, we discuss the diagnostic utility of currently used serum iron indices and emerging alternative markers of iron stores. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. 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.

  2. Next Generation Sequencing approach to molecular diagnosis of Duchenne muscular dystrophy; identification of a novel mutation.

    Science.gov (United States)

    Ebrahimzadeh-Vesal, Reza; Teymoori, Atieh; Azimi-Nezhad, Mohsen; Hosseini, Forough Sadat

    2018-02-20

    Duchenne Muscular Dystrophy (DMD; MIM 310200) is one of the most common and severe type of hereditary muscular dystrophies. The disease is caused by mutations in the dystrophin gene. The dystrophin gene is associated with X-linked recessive Duchenne and Becker muscular dystrophy. This disease occurs almost exclusively in males. The clinical symptoms of muscle weakness usually begin at childhood. The main symptoms of this disorder are gradually muscular weakness. The affected patients have inability to standing up and walking. Death is usually due to respiratory infection or cardiomyopathy. In this article, we have reported the discovery of a new nonsense mutation that creates abnormal stop codon in the dystrophin gene. This mutation was detected using Next Generation Sequencing (NGS) technique. The subject was a 17-year-old male with muscular dystrophy that who was suspected of having DMD. He was referred to Hakim medical genetics center of Neyshabur, IRAN. Copyright © 2017. Published by Elsevier B.V.

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

    Directory of Open Access Journals (Sweden)

    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.

  4. Iris features-based heart disease diagnosis by computer vision

    Science.gov (United States)

    Nguchu, Benedictor A.; Li, Li

    2017-07-01

    The study takes advantage of several new breakthroughs in computer vision technology to develop a new mid-irisbiomedical platform that processes iris image for early detection of heart-disease. Guaranteeing early detection of heart disease provides a possibility of having non-surgical treatment as suggested by biomedical researchers and associated institutions. However, our observation discovered that, a clinical practicable solution which could be both sensible and specific for early detection is still lacking. Due to this, the rate of majority vulnerable to death is highly increasing. The delayed diagnostic procedures, inefficiency, and complications of available methods are the other reasons for this catastrophe. Therefore, this research proposes the novel IFB (Iris Features Based) method for diagnosis of premature, and early stage heart disease. The method incorporates computer vision and iridology to obtain a robust, non-contact, nonradioactive, and cost-effective diagnostic tool. The method analyzes abnormal inherent weakness in tissues, change in color and patterns, of a specific region of iris that responds to impulses of heart organ as per Bernard Jensen-iris Chart. The changes in iris infer the presence of degenerative abnormalities in heart organ. These changes are precisely detected and analyzed by IFB method that includes, tensor-based-gradient(TBG), multi orientations gabor filters(GF), textural oriented features(TOF), and speed-up robust features(SURF). Kernel and Multi class oriented support vector machines classifiers are used for classifying normal and pathological iris features. Experimental results demonstrated that the proposed method, not only has better diagnostic performance, but also provides an insight for early detection of other diseases.

  5. 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.

  6. Use of targeted exome sequencing in genetic diagnosis of Chinese familial hypercholesterolemia.

    Directory of Open Access Journals (Sweden)

    Wen-Feng Wu

    Full Text Available Familial hypercholesterolemia is an autosomal dominant inherited disease characterized by elevated plasma low-density lipoprotein cholesterol (LDL-C. It is mainly caused by mutations of the low-density lipoprotein receptor (LDLR gene. Currently, the methods of whole genome sequencing or whole exome sequencing for screening mutations in familial hypercholesterolemia are not applicable in China due to high cost. We performed targeted exome sequencing of 167 genes implicated in the homozygous phenotype of a proband pedigree to identify candidate mutations, validated them in the family of the proband, studied the functions of the mutant protein, and followed up serum lipid levels after treatment. We discovered that exon 9 c.1268 T>C and exon 8 c.1129 T>G compound heterozygous mutations in the LDLR gene in the proband derived from the mother and father, respectively, in which the mutation of c.1129 T>G has not been reported previously. The mutant LDL-R protein had 57% and 52% binding and internalization functions, respectively, compared with that of the wild type. After 6 months of therapy, the LDL-C level of the proband decreased by more than 50% and the LDL-C of the other family members with heterozygous mutation also reduced to normal. Targeted exome sequencing is an effective method for screening mutation genes in familial hypercholesterolemia. The exon 8 and 9 mutations of the LDLR gene were pedigree mutations. The functions of the mutant LDL-R protein were decreased significantly compared with that of the wild type. Simvastatin plus ezetimibe was proven safe and effective in this preschool-age child.

  7. Diagnosis of Ebola Virus Disease: Past, Present, and Future

    Science.gov (United States)

    Brooks, Tim J. G.

    2016-01-01

    SUMMARY Laboratory diagnosis of Ebola virus disease plays a critical role in outbreak response efforts; however, establishing safe and expeditious testing strategies for this high-biosafety-level pathogen in resource-poor environments remains extremely challenging. Since the discovery of Ebola virus in 1976 via traditional viral culture techniques and electron microscopy, diagnostic methodologies have trended toward faster, more accurate molecular assays. Importantly, technological advances have been paired with increasing efforts to support decentralized diagnostic testing capacity that can be deployed at or near the point of patient care. The unprecedented scope of the 2014-2015 West Africa Ebola epidemic spurred tremendous innovation in this arena, and a variety of new diagnostic platforms that have the potential both to immediately improve ongoing surveillance efforts in West Africa and to transform future outbreak responses have reached the field. In this review, we describe the evolution of Ebola virus disease diagnostic testing and efforts to deploy field diagnostic laboratories in prior outbreaks. We then explore the diagnostic challenges pervading the 2014-2015 epidemic and provide a comprehensive examination of novel diagnostic tests that are likely to address some of these challenges moving forward. PMID:27413095

  8. Computerized tomography - its validity in the diagnosis of gastroenterologic disease

    International Nuclear Information System (INIS)

    Schoppe, W.D.; Jungblut, R.M.

    1982-01-01

    The development of faster CT-machines with scantimes below five seconds and the introduction of different techniques for CT examinations (e.g. application of oral and intravenous contrast material) have influenced diagnostic procedures in medicine. On the other hand there are only a few procedures that have been replaced by CT, e.g. pneumoventriculography, pneumoretroperitoneum. In gastronenterology well established diagnostic methods as ultrasound, ERCP, PTC, barium meal and barium enema are known to have a high accuracy. CT has to be compared with these techniques and therefore its value in the diagnostic spectrum is still under investigation. So far every single method has primary or secondary indications. But it should be the aim of further studies to minimize risk and radiation dose of diagnostic procedures. Using CT this is possible, especially in intraabdominal diseases. From the present knowledge the validity of CT in the diagnosis of gastroenterologic diseases is discussed. The given recommendations might change in the future as result of ongoing investigations, technical improvements, wider distribution of CT machines and broader experiences of physicians. (orig.) [de

  9. DIAGNOSIS OF ENDOCRINE DISEASE: Expanding the cause of hypopituitarism.

    Science.gov (United States)

    Pekic, Sandra; Popovic, Vera

    2017-06-01

    Hypopituitarism is defined as one or more pituitary hormone deficits due to a lesion in the hypothalamic-pituitary region. By far, the most common cause of hypopituitarism associated with a sellar mass is a pituitary adenoma. A high index of suspicion is required for diagnosing hypopituitarism in several other conditions such as other massess in the sellar and parasellar region, brain damage caused by radiation and by traumatic brain injury, vascular lesions, infiltrative/immunological/inflammatory diseases (lymphocytic hypophysitis, sarcoidosis and hemochromatosis), infectious diseases and genetic disorders. Hypopituitarism may be permanent and progressive with sequential pattern of hormone deficiencies (radiation-induced hypopituitarism) or transient after traumatic brain injury with possible recovery occurring years from the initial event. In recent years, there is increased reporting of less common and less reported causes of hypopituitarism with its delayed diagnosis. The aim of this review is to summarize the published data and to allow earlier identification of populations at risk of hypopituitarism as optimal hormonal replacement may significantly improve their quality of life and life expectancy. © 2017 European Society of Endocrinology.

  10. Deep sequencing of foot-and-mouth disease virus reveals RNA sequences involved in genome packaging.

    Science.gov (United States)

    Logan, Grace; Newman, Joseph; Wright, Caroline F; Lasecka-Dykes, Lidia; Haydon, Daniel T; Cottam, Eleanor M; Tuthill, Tobias J

    2017-10-18

    Non-enveloped viruses protect their genomes by packaging them into an outer shell or capsid of virus-encoded proteins. Packaging and capsid assembly in RNA viruses can involve interactions between capsid proteins and secondary structures in the viral genome as exemplified by the RNA bacteriophage MS2 and as proposed for other RNA viruses of plants, animals and human. In the picornavirus family of non-enveloped RNA viruses, the requirements for genome packaging remain poorly understood. Here we show a novel and simple approach to identify predicted RNA secondary structures involved in genome packaging in the picornavirus foot-and-mouth disease virus (FMDV). By interrogating deep sequencing data generated from both packaged and unpackaged populations of RNA we have determined multiple regions of the genome with constrained variation in the packaged population. Predicted secondary structures of these regions revealed stem loops with conservation of structure and a common motif at the loop. Disruption of these features resulted in attenuation of virus growth in cell culture due to a reduction in assembly of mature virions. This study provides evidence for the involvement of predicted RNA structures in picornavirus packaging and offers a readily transferable methodology for identifying packaging requirements in many other viruses. Importance In order to transmit their genetic material to a new host, non-enveloped viruses must protect their genomes by packaging them into an outer shell or capsid of virus-encoded proteins. For many non-enveloped RNA viruses the requirements for this critical part of the viral life cycle remain poorly understood. We have identified RNA sequences involved in genome packaging of the picornavirus foot-and-mouth disease virus. This virus causes an economically devastating disease of livestock affecting both the developed and developing world. The experimental methods developed to carry out this work are novel, simple and transferable to the

  11. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.)

  13. 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

  14. Autoinflammatory diseases: update on classification diagnosis and management.

    Science.gov (United States)

    Pathak, Shelly; McDermott, Michael F; Savic, Sinisa

    2017-01-01

    The spectrum of systemic autoinflammatory disorders broadens continually. In part, this is due to the more widespread application of massive parallel sequencing, helping with novel gene discovery in this and other areas of rare diseases. Some of the conditions that have been described fit neatly into a conventional idea of autoinflammation. Others, such as interferon-mediated autoinflammatory diseases, are broadening the concept which we consider to be autoinflammatory disorders. There is also a widening of the clinical phenotypes associated with certain genetic mutations, as genetic testing is used more regularly and increasing numbers of patients are screened. It is also increasingly evident that both autoinflammatory and autoimmune problems are frequently seen as complications of primary immunodeficiency disorders. The aim of this review is to provide an update on some recently discovered conditions and to discuss how these disorders help to define the concept of autoinflammation. The review will also cover recent discoveries in the biology of innate-immune-mediated inflammation and describe how this has provided the biological rationale for using anti-interleukin-1 therapies in the treatment of many such conditions. Finally, we discuss the importance of recognising somatic mutations as causes of autoinflammatory clinical phenotypes and provide practical advice on how this could be tackled in everyday clinical practice. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  15. The Sequence Effect in Parkinson’s Disease

    Directory of Open Access Journals (Sweden)

    Suk Yun Kang

    2011-05-01

    Full Text Available Background and Purpose The sequence effect (SE in Parkinson’s disease (PD denotes progressive slowness in speed or progressive decrease in amplitude of repetitive movements. It is a well-known feature of bradykinesia and is considered unique in PD. Until now, it was well-documented in advanced PD, but not in drug-naïve PD. The aim of this study is to know whether the SE can also be measured in drug-naïve PD. Methods We measured the SE with a computer-based, modified Purdue pegboard in 4 drug-naïve PD patients, which matched our previous study with advanced PD patients. Results We observed progressive slowness during movement, that is, SE. Statistical analysis showed a strong statistical trend toward the SE with the right hand, but no significance with the left hand. There was no statistical significance of SE with either the more or less affected hands. Conclusions These results indicate that the SE can be identified in drug-naïve PD, as well as in advanced PD, with objective measurements and support the idea that the SE is a feature in PD observed during the early stage of the disease without medication.

  16. Overview of biomarkers for diagnosis and monitoring of celiac disease.

    Science.gov (United States)

    Brusca, Ignazio

    2015-01-01

    Among the adverse reactions caused by wheat, celiac disease (CD) is the longest studied and best-known pathology. The more recently defined non-celiac gluten sensitivity (NCGS) presents with symptoms which are often indistinguishable from CD. Diagnosis of CD is based on serologic, molecular, and bioptic testing. The IgA anti-transglutaminase (tTG) test is considered highly important, as it shows high sensitivity and specificity and its levels correlate to the degree of intestinal damage. Small bowel biopsy can be avoided in symptomatic patients with IgA anti-tTG levels above 10× the manufacturer's cut-off. Recently, tests of anti-deamidated peptides of gliadin (DGP) have replaced classic anti-native gliadin (AGA) tests. DGP assays have a considerably higher diagnostic accuracy than AGA assays, especially in the IgG class, and can replace anti-tTG tests in patients with selective IgA deficiency. The combination of IgG anti-DGP plus IgA anti-tTG assays show greater sensitivity than a single test, with very high specificity. EMA tests have great diagnostic accuracy but are not recommended by all the latest guidelines because they are observer dependent. Biopsy must still be considered the gold standard for CD diagnosis. HLA-DQ genotyping can be used to screen asymptomatic children and in cases of histology/serology disagreement. About half of NCGS patients are DQ2 positive and have IgG AGA. To diagnose NCGS, first CD and wheat allergy must be excluded; then the wheat dependence of symptoms must be verified by a gluten-free diet and subsequent gluten challenge. © 2015 Elsevier Inc. All rights reserved.

  17. Amyloid β oligomers in Alzheimer's disease pathogenesis, treatment, and diagnosis.

    Science.gov (United States)

    Viola, Kirsten L; Klein, William L

    2015-02-01

    offer appealing targets for therapeutics and diagnostics. Promising therapeutic strategies include use of CNS insulin signaling enhancers to protect against the presence of toxins and elimination of the toxins through use of highly specific AβO antibodies. An AD-dependent accumulation of AβOs in CSF suggests their potential use as biomarkers and new AβO probes are opening the door to brain imaging. Overall, current evidence indicates that Aβ oligomers provide a substantive molecular basis for the cause, treatment and diagnosis of Alzheimer's disease.

  18. 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 ...

  19. 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

  20. 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...

  1. Diagnosis of ALG12-CDG by exome sequencing in a case of severe skeletal dysplasia

    Directory of Open Access Journals (Sweden)

    Chaya Murali

    2014-01-01

    Full Text Available Congenital Disorder of Glycosylation type Ig (ALG12-CDG is part of a group of autosomal recessive conditions caused by deficiency of proteins involved in the assembly of dolichol-oligosaccharides used for protein N-glycosylation. In ALG12-CDG, the enzyme affected is encoded by the ALG12 gene. Affected individuals present clinically with neurodevelopmental delay, growth retardation, immune deficiency, male genital hypoplasia, and cardiomyopathy. A total of six individuals have been reported in the literature. Here, we present an infant with rhizomelic short stature, talipes equinovarus, platyspondyly, and joint dislocations. The infant had marked under-ossification of the pubic bones. Exome sequencing was performed and two deletions, each resulting in a frameshift, were found in ALG12. A review of the literature revealed two infants with ALG12-CDG and a severe skeletal dysplasia, including under-ossification of cervical vertebrae, pubic bones, and knees; in addition to talipes equinovarus and rhizomelic short stature. The phenotype of the individual we describe resembles pseudodiastrophic dysplasia and we discuss similarities and differences between ALG12-CDG and pseudodiastrophic dysplasia. The differential diagnosis in selected undiagnosed skeletal dysplasias should include CDGs.

  2. 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

  3. 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....

  4. Computed tomography in the diagnosis of adrenal disease

    International Nuclear Information System (INIS)

    Hirosawa, Kunihiro

    1980-01-01

    From June 1977 through June 1980, sixty-one patients who were suspected to have adrenal diseases were examined with a CT scanner at Tokyo Women's Medical College. They consist of twenty five primary hyperaldosteronism, eight Cushing's syndrome, twenty pheochromocytoma and eight other adrenal masses. Ten patients were unexpectedly found to have adrenal lesion or mass simulating an adrenal tumor on CT performed for other reasons. CT findings were reviewed and correlated with surgical findings, postmortem studies and with results of other diagnostic modalities. 1. Primary hyperaldosteronism. Fifteen of twenty-five patients underwent surgery. Thirteen were pathologically proved to have aldosteronoma and two hyperplasia. Ten of thirteen patients with aldosteronoma were correctly diagnosed by CT scan. 2. Cushing's syndrome. Unilateral adenoma was correctly diagnosed preoperatively by CT scan on two surgically proved cases. CT showed marked enlargement of the adrenal gland with multiple nodules measuring less than 2 cm in diameter in the patient with nodular hyperplasia. Four patients were found to have normal-appearing adrenals with CT scan. 3. Pheochromocytoma. Three adrenal and one juxta-adrenal pheochromocytomas were detected by CT scan. Pheochromocytoma was considered as very unlikely on the basis of CT scan as well as further clinical investigation in sixteen patients. The value of CT scan for localization of extraadrenal pheochromocytoma remains established. 4. Miscellaneous adrenal disease and extra-adrenal masses simulating adrenal lesions. Two primary carcinoma, two bilateral metastasis, two adrenal neuroblastoma and a cyst were detected by CT scan. In cases with a huge mass, however, the origin and histologic diagnosis could not always be determined by CT scan. (author)

  5. [Application of Next Generation Sequencing for AML/MDS Diagnosis and Treatment].

    Science.gov (United States)

    Cheng, Huan-Chen; Liu, Sheng-Wei; Liu, Yu; Zhao, Xue-Fei; Li, Wei; Qiu, Lin; Ma, Jun

    2017-12-01

    To detect the mutations of AML/MDS- related genes by using next generation sequencing (NGS), to analyze the mutation levels of each genes in the AML/MDS and the sensitivity of NGS, and to evaluate the feasibility of gene mutations for monitoring the MRD and predicating the progression of diseases. The specimens were collected from primary AML (68 cases) and MDS (57 cases) patients from August 2015 to June 2016 in the Harbin Institute of Hematology and Oncology. The mutations of 22 related genes were detected by using AML/MDS-NGS chips. TET2 gene showed the highest mutation rate in AML (55.9%) and MDS (56.1%). The gene mutations were as follows: CEBPA (11.8%), DNMT3A (7.4%), C-KIT (7.4%) and FLT3-ITD (7.4%) in AML, and U2AF1 (10.5%) and SRSF2 (10.5%) in MDS. All the genes had specific mutation sites except TP53 and CEBPA. The mutations of FLT3, C-KIT and CEBPA became negative in the 5 AML patients in remission when compared with those at primary attack, but the mutation rate of TET2 gene was not obviously changed, whereas the mutation rate of the 5 MDS patients was not significantly changed. The new gene mutations appeared in 3 MDS patients with disease progression, but the mutation rate was not changed significantly in the disease progression. The gene mutation rate still has not been changed significantly even after remission. Both AML and MDS have their own specific mutated genes and sites. Some gene mutations, such as CEBPA, can be used as an effective indicator to monitoring MRD in AML patients, but those only used for the evaluation of the disease progression and prognosis in MDS patients.

  6. Gastroesophageal reflux disease in 2006. The imperfect diagnosis

    International Nuclear Information System (INIS)

    Boyle, John T.

    2006-01-01

    There continues to be significant controversy related to diagnostic testing for gastroesophageal reflux disease (GERD). Clearly, barium contrast fluoroscopy is superior to any other test in defining the anatomy of the upper gastrointestinal (UGI) tract. Although fluoroscopy can demonstrate gastroesophageal reflux (GER), this observation does not equate to GERD. Fluoroscopy time should not be prolonged to attempt to demonstrate GER during barium contrast radiography. There are no data to justify prolonging fluoroscopy time to perform provocative maneuvers to demonstrate reflux during barium contrast UGI series. Symptoms of GERD may be associated with physiologic esophageal acid exposure measured by intraesophageal pH monitoring, and a significant percentage of patients with abnormal esophageal acid exposure have no or minimal clinical symptoms of reflux. Abnormal acid exposure defined by pH monitoring over a 24-h period does not equate to GERD. In clinical practice presumptive diagnosis of GERD is reasonably assumed by substantial reduction or elimination of suspected reflux symptoms during therapeutic trial of acid reduction therapy. (orig.)

  7. Diagnosis of inflammatory bowel disease: Potential role of molecular biometrics.

    Science.gov (United States)

    M'Koma, Amosy E

    2014-11-27

    Accurate diagnosis of predominantly colonic inflammatory bowel disease (IBD) is not possible in 30% of patients. For decades, scientists have worked to find a solution to improve diagnostic accuracy for IBD, encompassing Crohn's colitis and ulcerative colitis. Evaluating protein patterns in surgical pathology colectomy specimens of colonic mucosal and submucosal compartments, individually, has potential for diagnostic medicine by identifying integrally independent, phenotype-specific cellular and molecular characteristics. Mass spectrometry (MS) and imaging (I) MS are analytical technologies that directly measure molecular species in clinical specimens, contributing to the in-depth understanding of biological molecules. The biometric-system complexity and functional diversity is well suited to proteomic and diagnostic studies. The direct analysis of cells and tissues by Matrix-Assisted-Laser Desorption/Ionization (MALDI) MS/IMS has relevant medical diagnostic potential. MALDI-MS/IMS detection generates molecular signatures obtained from specific cell types within tissue sections. Herein discussed is a perspective on the use of MALDI-MS/IMS and bioinformatics technologies for detection of molecular-biometric patterns and identification of differentiating proteins. I also discuss a perspective on the global challenge of transferring technologies to clinical laboratories dealing with IBD issues. The significance of serologic-immunometric advances is also discussed.

  8. Rotator cuff disease – basics of diagnosis and treatment

    Directory of Open Access Journals (Sweden)

    Robert E. Boykin

    2010-03-01

    Full Text Available Rotator cuff (RTC disease is a particularly prevalent cause of shoulder pain and weakness presenting to primary care physicians, internists, rheumatologists, and orthopedists. An understanding of the anatomy of the RTC tendons and the underlying pathogenesis aids in the diagnosis, which is based largely on history and specific physical examination tests. Imaging may further define the pathology and aid in the evaluation of other sources of shoulder pain. Injuries to the RTC range from tendonitis to partial thickness tears to full thickness tears. The majority of patients with impingement and some cases of partial thickness tears may be managed effectively with non-operative measures including non-steroidal anti-inflammatory drugs, local injections, and physical therapy. Predictors of a good outcome with non-operative treatment include pre-injury strength, ability to raise the arm to the level of the shoulder, and a more acute presentation. Persistent symptoms may require operative intervention including debridement, subacromial decompression, and/or RTC repair. Acute full thickness tears in younger patients in addition to failed non-operative management of full thickness tears in older patients are the most likely to require surgery, which may be done open or arthroscopically. The majority of tears are amenable to the less invasive arthroscopic method, which yields good success rates and high patient satisfaction.

  9. Histologic diagnosis of metabolic bone diseases: bone histomorphometry

    Directory of Open Access Journals (Sweden)

    L. Dalle Carbonare

    2011-09-01

    Full Text Available Histomorphometry or quantitative histology is the analysis on histologic sections of bone resorption parameters, formation and structure. It is the only technique that allows a dynamic evaluation of the activity of bone modelling after labelling with tetracycline. Moreover, the new measurement procedures through the use of the computer allow an assessment of bone microarchitecture too. Histomorphometric bone biopsy is a reliable and well-tolerated procedure. Complications are reported only in 1% of the subjects (hematoma, pain, transient neuralgia. Histomorphometry is used to exclude or confirm the diagnosis of osteomalacia. It is employed in the evaluation of bone damage associated with particular treatments (for example, anticonvulsants or in case of rare bone diseases (osteogenesis imperfecta, systemic mastocytosis. It is also an essential approach when clinical, biochemical and other diagnostic data are not consistent. Finally, it is a useful method to understand the pathophysiologic mechanisms of drugs. The bone sample is taken at the level of iliac crest under local anesthesia. It is then put into methyl-metacrilate resin where the sections are prepared for the microscopic analysis of the various histomorphometric parameters.

  10. Gastroesophageal reflux disease in 2006. The imperfect diagnosis

    Energy Technology Data Exchange (ETDEWEB)

    Boyle, John T. [Children' s Hospital of Alabama, Division of Pediatric Gastroenterology, Birmingham, AL (United States); University of Alabama-Birmingham School of Medicine, Division of Pediatric Gastroenterology, Birmingham, AL (United States)

    2006-09-15

    There continues to be significant controversy related to diagnostic testing for gastroesophageal reflux disease (GERD). Clearly, barium contrast fluoroscopy is superior to any other test in defining the anatomy of the upper gastrointestinal (UGI) tract. Although fluoroscopy can demonstrate gastroesophageal reflux (GER), this observation does not equate to GERD. Fluoroscopy time should not be prolonged to attempt to demonstrate GER during barium contrast radiography. There are no data to justify prolonging fluoroscopy time to perform provocative maneuvers to demonstrate reflux during barium contrast UGI series. Symptoms of GERD may be associated with physiologic esophageal acid exposure measured by intraesophageal pH monitoring, and a significant percentage of patients with abnormal esophageal acid exposure have no or minimal clinical symptoms of reflux. Abnormal acid exposure defined by pH monitoring over a 24-h period does not equate to GERD. In clinical practice presumptive diagnosis of GERD is reasonably assumed by substantial reduction or elimination of suspected reflux symptoms during therapeutic trial of acid reduction therapy. (orig.)

  11. Diagnosis of coronary artery disease in hypertensive patients

    International Nuclear Information System (INIS)

    Cuocolo, A.; Esposito, S.; Acampora, C.; Squame, C.

    1988-01-01

    Exercise radionuclide ventriculography (ERV) is considered a superior non-invasive screening test for coronary artery disease (CAD). ERV showed, however, a low specificity in hypertensive patients (H). The diagnostic accuracy of EAR and thallium-201 myocardial scintigraphy (M) was evaluated in 23 patients (H) with chest pain and positive ECG-strees test. All patients underwent ERV and M, randomly, in different days. Finally, they all underwent coronary angiography: CAD was diagnosed in case of luminal narrowing ≥ 70% in 1 major coronary artery at least. Eleven patients had severe CAD. ERV was considered positive for CAD in presence of ex-induced abnormality of wall motion and/or in case of ex-induced ejection fraction increase ≤ 5% respect to the basal values. M was considered positive for CAD when perfusion defects were observed in early images only. ERV showed low diagnostic accuracy. On the contrary M had both sensibility and specificity, and a high positive and negative predictive value in the diagnosis of CAD. M is thus suggested as the non-invasive methodology of choice in hypertensive patients with suspected CAD

  12. 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

  13. 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 ...

  14. 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.

  15. Characteristics of the sequence effect in Parkinson's disease.

    Science.gov (United States)

    Kang, Suk Yun; Wasaka, Toshiaki; Shamim, Ejaz A; Auh, Sungyoung; Ueki, Yoshino; Lopez, Grisel J; Kida, Tetsuo; Jin, Seung-Hyun; Dang, Nguyet; Hallett, Mark

    2010-10-15

    The sequence effect (SE) in Parkinson's disease (PD) is progressive slowing of sequential movements. It is a feature of bradykinesia, but is separate from a general slowness without deterioration over time. It is commonly seen in PD, but its physiology is unclear. We measured general slowness and the SE separately with a computer-based, modified Purdue pegboard in 11 patients with advanced PD. We conducted a placebo-controlled, four-way crossover study to learn whether levodopa and repetitive transcranial magnetic stimulation (rTMS) could improve general slowness or the SE. We also examined the correlation between the SE and clinical fatigue. Levodopa alone and rTMS alone improved general slowness, but rTMS showed no additive effect on levodopa. Levodopa alone, rTMS alone, and their combination did not alleviate the SE. There was no correlation between the SE and fatigue. This study suggests that dopaminergic dysfunction and abnormal motor cortex excitability are not the relevant mechanisms for the SE. Additionally, the SE is not a component of clinical fatigue. Further work is needed to establish the physiology and clinical relevance of the SE. © 2010 Movement Disorder Society.

  16. Genetic Bases of Bicuspid Aortic Valve: The Contribution of Traditional and High-Throughput Sequencing Approaches on Research and Diagnosis.

    Science.gov (United States)

    Giusti, Betti; Sticchi, Elena; De Cario, Rosina; Magi, Alberto; Nistri, Stefano; Pepe, Guglielmina

    2017-01-01

    development of "BigData" analysis methods improving their interpretation and integration with clinical data represents a promising opportunity to increase the disease knowledge and diagnosis in monogenic and multifactorial complex traits. This review summarized the main knowledge on the BAV genetic bases, the role of genetic diagnosis in BAV patient managements and the crucial challenges for the comprehension of genetics of BAV in research and diagnosis.

  17. Genetic Bases of Bicuspid Aortic Valve: The Contribution of Traditional and High-Throughput Sequencing Approaches on Research and Diagnosis

    Directory of Open Access Journals (Sweden)

    Betti Giusti

    2017-08-01

    the development of “BigData” analysis methods improving their interpretation and integration with clinical data represents a promising opportunity to increase the disease knowledge and diagnosis in monogenic and multifactorial complex traits. This review summarized the main knowledge on the BAV genetic bases, the role of genetic diagnosis in BAV patient managements and the crucial challenges for the comprehension of genetics of BAV in research and diagnosis.

  18. 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.

  19. Extensive next-generation sequencing analysis in chronic lymphocytic leukemia at diagnosis: clinical and biological correlations

    Directory of Open Access Journals (Sweden)

    Gian Matteo Rigolin

    2016-09-01

    Full Text Available Abstract Background In chronic lymphocytic leukemia (CLL, next-generation sequencing (NGS analysis represents a sensitive, reproducible, and resource-efficient technique for routine screening of gene mutations. Methods We performed an extensive biologic characterization of newly diagnosed CLL, including NGS analysis of 20 genes frequently mutated in CLL and karyotype analysis to assess whether NGS and karyotype results could be of clinical relevance in the refinement of prognosis and assessment of risk of progression. The genomic DNA from peripheral blood samples of 200 consecutive CLL patients was analyzed using Ion Torrent Personal Genome Machine, a NGS platform that uses semiconductor sequencing technology. Karyotype analysis was performed using efficient mitogens. Results Mutations were detected in 42.0 % of cases with 42.8 % of mutated patients presenting 2 or more mutations. The presence of mutations by NGS was associated with unmutated IGHV gene (p = 0.009, CD38 positivity (p = 0.010, risk stratification by fluorescence in situ hybridization (FISH (p < 0.001, and the complex karyotype (p = 0.003. A high risk as assessed by FISH analysis was associated with mutations affecting TP53 (p = 0.012, BIRC3 (p = 0.003, and FBXW7 (p = 0.003 while the complex karyotype was significantly associated with TP53, ATM, and MYD88 mutations (p = 0.003, 0.018, and 0.001, respectively. By multivariate analysis, the multi-hit profile (≥2 mutations by NGS was independently associated with a shorter time to first treatment (p = 0.004 along with TP53 disruption (p = 0.040, IGHV unmutated status (p < 0.001, and advanced stage (p < 0.001. Advanced stage (p = 0.010, TP53 disruption (p < 0.001, IGHV unmutated status (p = 0.020, and the complex karyotype (p = 0.007 were independently associated with a shorter overall survival. Conclusions At diagnosis, an extensive biologic characterization including

  20. 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

  1. [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.

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  4. A model-based clustering method to detect infectious disease transmission outbreaks from sequence variation.

    Directory of Open Access Journals (Sweden)

    Rosemary M McCloskey

    2017-11-01

    Full Text Available Clustering infections by genetic similarity is a popular technique for identifying potential outbreaks of infectious disease, in part because sequences are now routinely collected for clinical management of many infections. A diverse number of nonparametric clustering methods have been developed for this purpose. These methods are generally intuitive, rapid to compute, and readily scale with large data sets. However, we have found that nonparametric clustering methods can be biased towards identifying clusters of diagnosis-where individuals are sampled sooner post-infection-rather than the clusters of rapid transmission that are meant to be potential foci for public health efforts. We develop a fundamentally new approach to genetic clustering based on fitting a Markov-modulated Poisson process (MMPP, which represents the evolution of transmission rates along the tree relating different infections. We evaluated this model-based method alongside five nonparametric clustering methods using both simulated and actual HIV sequence data sets. For simulated clusters of rapid transmission, the MMPP clustering method obtained higher mean sensitivity (85% and specificity (91% than the nonparametric methods. When we applied these clustering methods to published sequences from a study of HIV-1 genetic clusters in Seattle, USA, we found that the MMPP method categorized about half (46% as many individuals to clusters compared to the other methods. Furthermore, the mean internal branch lengths that approximate transmission rates were significantly shorter in clusters extracted using MMPP, but not by other methods. We determined that the computing time for the MMPP method scaled linearly with the size of trees, requiring about 30 seconds for a tree of 1,000 tips and about 20 minutes for 50,000 tips on a single computer. This new approach to genetic clustering has significant implications for the application of pathogen sequence analysis to public health, where

  5. IMMUNOHISTOCHEMISTRY VERSUS IMMUNOFLUORESENCE IN THE DIAGNOSIS OF AUTOIMMUNE BLISTERING DISEASES

    Directory of Open Access Journals (Sweden)

    Ana Maria Abreu Velez

    2013-11-01

    Full Text Available Introduction: In patients with autoimmune skin blistering diseases (ABDs, the diagnostic gold standard has classically been direct and indirect immunofluorescence (DIF and IIF, despite inherent technical problems of autofluorescence. Aim: We sought to overcome autofluorescence issues and compare the reliability of immunofluorescence versus immunohistochemistry (IHC staining in the diagnoses of these diseases. Methods: We tested via IHC for anti-human IgG, IgM, IgA, IgD, IgE, Kappa light chains, Lambda light chains, Complement/C3c, Complement/C1q, Complement/C3d, albumin and fibrinogen in 30 patients affected by a new variant of endemic pemphigus foliaceus in El Bagre, Colombia (El Bagre-EPF, and 30 control biopsies from the endemic area. We also tested archival biopsies from patients with ABDs whose diagnoses were made clinically, histopathologically and by DIF/IIF studies from 2 independent dermatopathology laboratories in the USA. Specifically, we tested 34 patients with bullous pemphigoid (BP, 18 with pemphigus vulgaris (PV, 8 with pemphigus foliaceus (PF, 14 with dermatitis herpetiformis (DH and 30 control skin samples from plastic esthetic surgery reduction surgeries. Results: The diagnostic correlation between IHC and DIF-IIF was almost 98% in most cases. IHC revealed evidence of autofluorescence around dermal blood vessels, dermal eccrine glands and neurovascular packages feeding skin appendices in ABDs; this autofluorescence may represent a non-specific immune response. Strong patterns of positivity were seen also in endothelial-mesenchymal cell junction-like structures, as well as between dermal fibrohistiocytic cells. In PV, we noted strong reactivity to neurovascular packages supplying sebaceous glands, as well as apocrine glands with edematous changes. Conclusions: We suggest that IHC is as reliable as DIF or IIF for the diagnosis of ABDs; our findings further suggest that what has previously been considered DIF/IIF autofluorescence

  6. 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.

  7. [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.

  8. 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...

  9. PCR analysis is superior to histology for diagnosis of Whipple's disease mimicking seronegative rheumatic diseases.

    Science.gov (United States)

    Lehmann, P; Ehrenstein, B; Hartung, W; Dragonas, C; Reischl, U; Fleck, M

    2017-03-01

    The diagnosis of Whipple's disease (WD) is commonly confirmed by histology demonstrating Periodic Acid Schiff (PAS)-positive macrophages in the duodenal mucosa. Analysis of intestinal tissue or other specimens using polymerase chain reaction (PCR) is a more sensitive method. However, the relevance of positive PCR findings is still controversial. Therefore, we evaluated the relevance of histology and PCR findings to establishing the diagnosis of WD in a series of WD patients initially presenting with suspected rheumatic diseases. Between 2006 and 2014, 20 patients with seronegative rheumatic diseases tested positive for Tropheryma whipplei (Tw) by PCR and/or histology and were enrolled in a retrospective analysis of the diagnostic value of both procedures. Seven of the 20 cases (35%) were diagnosed with 'classic' WD as indicated by PAS-positive macrophages. In the remaining 13 patients, the presence of Tw was detected by intestinal (n = 10) or synovial PCR analysis (n = 3). Two of the 20 patients (10%) with evidence of Tw did not respond to antibiotic therapy. They were not considered to suffer from WD. Therefore, relying only on histological findings of intestinal biopsies would have missed 11 (61%) of the 18 patients with WD in our cohort. In comparison, PCR of intestinal biopsies detected Tw-DNA in 14 (93%) of the 15 WD patients evaluated. Patients with a positive histology did not differ from PCR-positive patients with regard to sex, age, or duration of disease, but more often presented with gastrointestinal symptoms. A substantial number of WD patients present without typical intestinal histology findings. Additional PCR analysis of intestinal tissue or synovial fluid increased the sensitivity of the diagnostic evaluation and should be considered particularly in patients presenting with atypical seronegative rheumatic diseases and a high-risk profile for WD.

  10. Intra-Genomic Internal Transcribed Spacer Region Sequence Heterogeneity and Molecular Diagnosis in Clinical Microbiology.

    Science.gov (United States)

    Zhao, Ying; Tsang, Chi-Ching; Xiao, Meng; Cheng, Jingwei; Xu, Yingchun; Lau, Susanna K P; Woo, Patrick C Y

    2015-10-22

    Internal transcribed spacer region (ITS) sequencing is the most extensively used technology for accurate molecular identification of fungal pathogens in clinical microbiology laboratories. Intra-genomic ITS sequence heterogeneity, which makes fungal identification based on direct sequencing of PCR products difficult, has rarely been reported in pathogenic fungi. During the process of performing ITS sequencing on 71 yeast strains isolated from various clinical specimens, direct sequencing of the PCR products showed ambiguous sequences in six of them. After cloning the PCR products into plasmids for sequencing, interpretable sequencing electropherograms could be obtained. For each of the six isolates, 10-49 clones were selected for sequencing and two to seven intra-genomic ITS copies were detected. The identities of these six isolates were confirmed to be Candida glabrata (n=2), Pichia (Candida) norvegensis (n=2), Candida tropicalis (n=1) and Saccharomyces cerevisiae (n=1). Multiple sequence alignment revealed that one to four intra-genomic ITS polymorphic sites were present in the six isolates, and all these polymorphic sites were located in the ITS1 and/or ITS2 regions. We report and describe the first evidence of intra-genomic ITS sequence heterogeneity in four different pathogenic yeasts, which occurred exclusively in the ITS1 and ITS2 spacer regions for the six isolates in this study.

  11. 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.

  12. Differential diagnosis of neurodegenerative diseases using structural MRI data

    Directory of Open Access Journals (Sweden)

    Juha Koikkalainen

    2016-01-01

    The results prove that automatic quantification methods and computerized decision support methods are feasible for clinical practice and provide comprehensive information that may help clinicians in the diagnosis making.

  13. Hemichorea, parkinson's disease or somatoform disorder? A hard differential diagnosis

    Directory of Open Access Journals (Sweden)

    David Gonçalves Nordon

    2010-12-01

    Full Text Available ABSTRACT: The diagnosis of movement disorders can be quite complex, as its causes may be both organic and psychogenic. We present the case of a 62 year old woman, with a 12 year old history of movement disorder, whose treatment has been insufficient and possibly inadequate, and her diagnosis has been doubtful and not yet defined. We discuss our diagnostic methods and empirical treatments, looking for the best for our patient.

  14. Anemia of Chronic Disease and Iron Deficiency Anemia in Inflammatory Bowel Diseases: Pathophysiology, Diagnosis, and Treatment.

    Science.gov (United States)

    Murawska, Natalia; Fabisiak, Adam; Fichna, Jakub

    2016-05-01

    Anemia coexists with inflammatory bowel disease (IBD) in up to two-thirds of patients, significantly impairing quality of life. The most common types of anemia in patients with IBD are iron deficiency anemia and anemia of chronic disease, which often overlap. In most cases, available laboratory tests allow successful diagnosis of iron deficiency, where difficulties appear, recently established indices such as soluble transferrin-ferritin ratio or percentage of hypochromic red cells are used. In this review, we discuss the management of the most common types of anemia in respect of the latest available data. Thus, we provide the mechanisms underlying pathophysiology of these entities; furthermore, we discuss the role of hepcidin in developing anemia in IBD. Next, we present the treatment options for each type of anemia and highlight the importance of individual choice of action. We also focus on newly developed intravenous iron preparations and novel, promising drug candidates targeting hepcidin. Concurrently, we talk about difficulties in differentiating between the true and functional iron deficiency, and discuss tools facilitating the process. Finally, we emphasize the importance of proper diagnosis and treatment of anemia in IBD. We conclude that management of anemia in patients with IBD is tricky, and appropriate screening of patients regarding anemia is substantial.

  15. Searching for Factors that Distinguish Disease-Prone and Disease-Resistant Prions via Sequence Analysis

    Directory of Open Access Journals (Sweden)

    Lukasz Kurgan

    2008-01-01

    Full Text Available The exact mechanisms of prion misfolding and factors that predispose an individual to prion diseases are largely unknown. Our approach to identifying candidate factors in-silico relies on contrasting the C-terminal domain of PrPC sequences from two groups of vertebrate species: those that have been found to suffer from prion diseases, and those that have not. We propose that any significant differences between the two groups are candidate factors that may predispose individuals to develop prion disease, which should be further analyzed by wet-lab investigations. Using an array of computational methods we identified possible point mutations that could predispose PrPC to misfold into PrPSc. Our results include confirmatory findings such as the V210I mutation, and new findings including P137M, G142D, G142N, D144P, K185T, V189I, H187Y and T191P mutations, which could impact structural stability. We also propose new hypotheses that give insights into the stability of helix-2 and -3. These include destabilizing effects of Histidine and T188-T193 segment in helix-2 in the disease-prone prions, and a stabilizing effect of Leucine on helix-3 in the disease-resistant prions.

  16. 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.

  17. 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

  18. 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.

  19. Targeted Sequencing of Lung Function Loci in Chronic Obstructive Pulmonary Disease Cases and Controls.

    Directory of Open Access Journals (Sweden)

    María Soler Artigas

    Full Text Available Chronic obstructive pulmonary disease (COPD is the third leading cause of death worldwide; smoking is the main risk factor for COPD, but genetic factors are also relevant contributors. Genome-wide association studies (GWAS of the lung function measures used in the diagnosis of COPD have identified a number of loci, however association signals are often broad and collectively these loci only explain a small proportion of the heritability. In order to examine the association with COPD risk of genetic variants down to low allele frequencies, to aid fine-mapping of association signals and to explain more of the missing heritability, we undertook a targeted sequencing study in 300 COPD cases and 300 smoking controls for 26 loci previously reported to be associated with lung function. We used a pooled sequencing approach, with 12 pools of 25 individuals each, enabling high depth (30x coverage per sample to be achieved. This pooled design maximised sample size and therefore power, but led to challenges during variant-calling since sequencing error rates and minor allele frequencies for rare variants can be very similar. For this reason we employed a rigorous quality control pipeline for variant detection which included the use of 3 independent calling algorithms. In order to avoid false positive associations we also developed tests to detect variants with potential batch effects and removed them before undertaking association testing. We tested for the effects of single variants and the combined effect of rare variants within a locus. We followed up the top signals with data available (only 67% of collapsing methods signals in 4,249 COPD cases and 11,916 smoking controls from UK Biobank. We provide suggestive evidence for the combined effect of rare variants on COPD risk in TNXB and in sliding windows within MECOM and upstream of HHIP. These findings can lead to an improved understanding of the molecular pathways involved in the development of COPD.

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

    Directory of Open Access Journals (Sweden)

    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.

  1. Echocardiography as an approach for canine cardiac disease diagnosis

    Directory of Open Access Journals (Sweden)

    P. Singh

    2014-11-01

    Full Text Available Aim: The aim of the study was to establish the methods for diagnosis various canine cardiac ailments using echocardiography. Materials and Methods: M-mode, two-dimensional echocardiography and Doppler studies were performed on 10 cases. Dogs showing signs of cardiac ailment either clinically, radiographic or via electrocardiographic examination were selected for study. Right parasternal short axis view was used for echocardiographic measurements. Right parasternal long axis and left parasternal apical views were used for Doppler studies. Doppler studies were performed at the level of aortic valve and atrioventricular valves for semi quantitative diagnosis of regurgitation. Results: Dogs were found affected with dilated cardiomyopathy (DCM (n=5, pericardial effusion (PE (n=1, combined PE and DCM (n=2 and remaining two showed abnormality on radiographic or electrographically evaluation but were found out to be normal echocardiographically (n=2. Conclusion: Echocardiography is an effective tool for diagnosis of various heart ailments.

  2. 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...

  3. 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.

  4. 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...

  5. Diagnosis and misdiagnosis of adult neuronal ceroid lipofuscinosis (Kufs disease)

    NARCIS (Netherlands)

    Berkovic, Samuel F.; Staropoli, John F.; Carpenter, Stirling; Oliver, Karen L.; Kmoch, Stanislav; Anderson, Glenn W.; Damiano, John A.; Hildebrand, Michael S.; Sims, Katherine B.; Cotman, Susan L.; Bahlo, Melanie; Smith, Katherine R.; Cadieux-Dion, Maxime; Cossette, Patrick; Jedlickova, Ivana; Pristoupilova, Anna; Mole, Sara E.; Koning, Klaziena

    2016-01-01

    Objective: To critically re-evaluate cases diagnosed as adult neuronal ceroid lipofuscinosis (ANCL) in order to aid clinicopathologic diagnosis as a route to further gene discovery. Methods: Through establishment of an international consortium we pooled 47 unsolved cases regarded by referring

  6. Usher syndrome: an effective sequencing approach to establish a genetic and clinical diagnosis.

    Science.gov (United States)

    Lenarduzzi, S; Vozzi, D; Morgan, A; Rubinato, E; D'Eustacchio, A; Osland, T M; Rossi, C; Graziano, C; Castorina, P; Ambrosetti, U; Morgutti, M; Girotto, G

    2015-02-01

    Usher syndrome is an autosomal recessive disorder characterized by retinitis pigmentosa, sensorineural hearing loss and, in some cases, vestibular dysfunction. The disorder is clinically and genetically heterogeneous and, to date, mutations in 11 genes have been described. This finding makes difficult to get a precise molecular diagnosis and offer patients accurate genetic counselling. To overcome this problem and to increase our knowledge of the molecular basis of Usher syndrome, we designed a targeted resequencing custom panel. In a first validation step a series of 16 Italian patients with known molecular diagnosis were analysed and 31 out of 32 alleles were detected (97% of accuracy). After this step, 31 patients without a molecular diagnosis were enrolled in the study. Three out of them with an uncertain Usher diagnosis were excluded. One causative allele was detected in 24 out 28 patients (86%) while the presence of both causative alleles characterized 19 patients out 28 (68%). Sixteen novel and 27 known alleles were found in the following genes: USH2A (50%), MYO7A (7%), CDH23 (11%), PCDH15 (7%) and USH1G (2%). Overall, on the 44 patients the protocol was able to characterize 74 alleles out of 88 (84%). These results suggest that our panel is an effective approach for the genetic diagnosis of Usher syndrome leading to: 1) an accurate molecular diagnosis, 2) better genetic counselling, 3) more precise molecular epidemiology data fundamental for future interventional plans. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. 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

  8. 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...

  9. A Data Mining Approach for Acoustic Diagnosis of Cardiopulmonary Disease

    Science.gov (United States)

    2008-06-01

    technology offered new methods to diagnose patients with lung diseases , the use of a stethoscope for auscultation waned in popularity and methods such as...lung sounds that were outside the normal range. The investigators found that the sensitivity for detection of respiratory disease rose from 71% to... diseases which can be costly and harmful to the patient because of over medicating. The “smart” stethoscope will help resolve some of these

  10. Diagnosis and treatment of chronic inflammatory diseases of parodontium

    International Nuclear Information System (INIS)

    Khitrov, V.Yu.; Zabolotnyj, A.I.; Khamidullina, S.A.

    1995-01-01

    Chronic inflammatory diseases of paradontium have the higher share in the structure of paradontal tissue injuries. The state of bone paradontium is monitored using roentgenographic techniques. The clinical picture of chronic inflammatory diseases consists of the signs of injury of different components of parodontium: gum, periodontitis and alveo bone. The treatment of patients in aimed at eliminating the symptoms of the disease recovery of masticatory ability and prevention of recurrences

  11. 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)

  12. Diagnosis of Lynch Syndrome: Genetic Testing Identifies a Potentially Deadly Hereditary Disease

    Science.gov (United States)

    ... of Lynch Syndrome Follow us A Diagnosis of Lynch Syndrome Genetic testing identifies a potentially deadly hereditary disease ... helped Jack learn what was wrong. Jack had Lynch Syndrome—an inherited disorder. Lynch Syndrome increases the risk ...

  13. 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

  14. Systems genetics of complex diseases using RNA-sequencing methods

    DEFF Research Database (Denmark)

    Mazzoni, Gianluca; Kogelman, Lisette; Suravajhala, Prashanth

    2015-01-01

    Next generation sequencing technologies have enabled the generation of huge quantities of biological data, and nowadays extensive datasets at different ‘omics levels have been generated. Systems genetics is a powerful approach that allows to integrate different ‘omics level and understand the bio...

  15. Potentialities of radioisotope aniocardiography in diagnosis of acquired heart diseases

    International Nuclear Information System (INIS)

    Malov, G.A.; Mikaelyan, R.S.; Dumpe, A.N.

    1980-01-01

    On the base of the examination of 40 patients with acquired heart diseases and 5 people without heart diseases for control determined are the most charactreristic signs of the acquired heart disease of visual observation on RPP transit (albumin of human serum labelled by sup(99m)Tc) through the heart cavities and magistral vessels. It is shown that there is a close connection between central and intracardial hemodynamics which permjts to judge on the cardiac output on the base of mean circulation time (MCT). Radioisotopic angiocardiography permits to find redistribution of lung blood flow in patients with acquired heart diseases, which can serve as indirect index of long hypertension

  16. Diagnosis of Grave's disease with pulmonary hypertension on chest CT.

    Science.gov (United States)

    Lee, Hwa Yeon; Yoo, Seung Min; Kim, Hye Rin; Chun, Eun Ju; White, Charles S

    To evaluate the diagnostic accuracy of chest CT findings to diagnose Grave's disease in pulmonary hypertension. We retrospectively evaluated chest CT and the medical records of 13 patients with Grave's disease with (n=6) or without pulmonary hypertension (n=7) and in 17 control patients. Presence of iso-attenuation of diffusely enlarged thyroid glands compared with adjacent neck muscle on non-enhanced CT as a diagnostic clue of Grave's disease, and assessment of pulmonary hypertension on CT has high diagnostic accuracy. Chest CT has the potential to diagnose Grave's disease with pulmonary hypertension in the absence of other information. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Extraintestinal manifestations of inflammatory bowel disease: epidemiology, diagnosis, and management

    DEFF Research Database (Denmark)

    Larsen, Signe; Bendtzen, Klaus; Nielsen, Ole Haagen

    2010-01-01

    ', 'bronchiectasis', 'bronchitis', 'cutaneous manifestations', 'erythema nodosum', 'extraintestinal manifestations', 'hyperhomocysteinemia', 'infliximab', 'iridocyclitis', 'lung disease', 'ocular manifestations', 'osteomalacia', 'pancreatitis', 'primary sclerosing cholangitis', 'renal stones', 'sulfasalazine...

  18. Integration of temporal and spatial properties of dynamic connectivity networks for automatic diagnosis of brain disease.

    Science.gov (United States)

    Jie, Biao; Liu, Mingxia; Shen, Dinggang

    2018-07-01

    Functional connectivity networks (FCNs) using resting-state functional magnetic resonance imaging (rs-fMRI) have been applied to the analysis and diagnosis of brain disease, such as Alzheimer's disease (AD) and its prodrome, i.e., mild cognitive impairment (MCI). Different from conventional studies focusing on static descriptions on functional connectivity (FC) between brain regions in rs-fMRI, recent studies have resorted to dynamic connectivity networks (DCNs) to characterize the dynamic changes of FC, since dynamic changes of FC may indicate changes in macroscopic neural activity patterns in cognitive and behavioral aspects. However, most of the existing studies only investigate the temporal properties of DCNs (e.g., temporal variability of FC between specific brain regions), ignoring the important spatial properties of the network (e.g., spatial variability of FC associated with a specific brain region). Also, emerging evidence on FCNs has suggested that, besides temporal variability, there is significant spatial variability of activity foci over time. Hence, integrating both temporal and spatial properties of DCNs can intuitively promote the performance of connectivity-network-based learning methods. In this paper, we first define a new measure to characterize the spatial variability of DCNs, and then propose a novel learning framework to integrate both temporal and spatial variabilities of DCNs for automatic brain disease diagnosis. Specifically, we first construct DCNs from the rs-fMRI time series at successive non-overlapping time windows. Then, we characterize the spatial variability of a specific brain region by computing the correlation of functional sequences (i.e., the changing profile of FC between a pair of brain regions within all time windows) associated with this region. Furthermore, we extract both temporal variabilities and spatial variabilities from DCNs as features, and integrate them for classification by using manifold regularized multi

  19. Molecular diagnosis of Usher syndrome: application of two different next generation sequencing-based procedures.

    Directory of Open Access Journals (Sweden)

    Danilo Licastro

    Full Text Available Usher syndrome (USH is a clinically and genetically heterogeneous disorder characterized by visual and hearing impairments. Clinically, it is subdivided into three subclasses with nine genes identified so far. In the present study, we investigated whether the currently available Next Generation Sequencing (NGS technologies are already suitable for molecular diagnostics of USH. We analyzed a total of 12 patients, most of which were negative for previously described mutations in known USH genes upon primer extension-based microarray genotyping. We enriched the NGS template either by whole exome capture or by Long-PCR of the known USH genes. The main NGS sequencing platforms were used: SOLiD for whole exome sequencing, Illumina (Genome Analyzer II and Roche 454 (GS FLX for the Long-PCR sequencing. Long-PCR targeting was more efficient with up to 94% of USH gene regions displaying an overall coverage higher than 25×, whereas whole exome sequencing yielded a similar coverage for only 50% of those regions. Overall this integrated analysis led to the identification of 11 novel sequence variations in USH genes (2 homozygous and 9 heterozygous out of 18 detected. However, at least two cases were not genetically solved. Our result highlights the current limitations in the diagnostic use of NGS for USH patients. The limit for whole exome sequencing is linked to the need of a strong coverage and to the correct interpretation of sequence variations with a non obvious, pathogenic role, whereas the targeted approach suffers from the high genetic heterogeneity of USH that may be also caused by the presence of additional causative genes yet to be identified.

  20. Molecular Diagnosis of Usher Syndrome: Application of Two Different Next Generation Sequencing-Based Procedures

    Science.gov (United States)

    Licastro, Danilo; Mutarelli, Margherita; Peluso, Ivana; Neveling, Kornelia; Wieskamp, Nienke; Rispoli, Rossella; Vozzi, Diego; Athanasakis, Emmanouil; D'Eustacchio, Angela; Pizzo, Mariateresa; D'Amico, Francesca; Ziviello, Carmela; Simonelli, Francesca; Fabretto, Antonella; Scheffer, Hans; Gasparini, Paolo; Banfi, Sandro; Nigro, Vincenzo

    2012-01-01

    Usher syndrome (USH) is a clinically and genetically heterogeneous disorder characterized by visual and hearing impairments. Clinically, it is subdivided into three subclasses with nine genes identified so far. In the present study, we investigated whether the currently available Next Generation Sequencing (NGS) technologies are already suitable for molecular diagnostics of USH. We analyzed a total of 12 patients, most of which were negative for previously described mutations in known USH genes upon primer extension-based microarray genotyping. We enriched the NGS template either by whole exome capture or by Long-PCR of the known USH genes. The main NGS sequencing platforms were used: SOLiD for whole exome sequencing, Illumina (Genome Analyzer II) and Roche 454 (GS FLX) for the Long-PCR sequencing. Long-PCR targeting was more efficient with up to 94% of USH gene regions displaying an overall coverage higher than 25×, whereas whole exome sequencing yielded a similar coverage for only 50% of those regions. Overall this integrated analysis led to the identification of 11 novel sequence variations in USH genes (2 homozygous and 9 heterozygous) out of 18 detected. However, at least two cases were not genetically solved. Our result highlights the current limitations in the diagnostic use of NGS for USH patients. The limit for whole exome sequencing is linked to the need of a strong coverage and to the correct interpretation of sequence variations with a non obvious, pathogenic role, whereas the targeted approach suffers from the high genetic heterogeneity of USH that may be also caused by the presence of additional causative genes yet to be identified. PMID:22952768

  1. Alcoholism: diagnosis, prognosis, epidemiology, and burden of the disease.

    Science.gov (United States)

    Beresford, Thomas P; Wongngamnit, Narin; Temple, Benjamin A

    2014-01-01

    To the clinician, alcoholism can appear as an amorphous entity that is confusing with respect to diagnosis, treatment prognosis, and the role of the health professional, despite its high incidence and associated morbidities and mortality when unrecognized or untreated. This chapter focuses on the clinical application of current knowledge, with the aim of being useful to the practitioner in working directly with patients for whom alcoholism may or may not be an already identified problem. It briefly reviews large-scale studies and then focuses on diagnosis and prognosis assessment and decision making. Also considered are current controversies in nomenclature and the chapter ends with an economic perspective with respect to healthcare and cost to society. As the introductory chapter, the goal is to provide a context of the scope of alcoholism and attendant problems for the rest of the chapters. © 2014 Elsevier B.V. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    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

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

    Directory of Open Access Journals (Sweden)

    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.

  4. Diagnosis and management of Addison's disease: insights gained ...

    African Journals Online (AJOL)

    The prevalence of Addison's disease in South Africa is lower than in Western countries. This is concerning, since patients could be dying, undiagnosed. Enhanced awareness of this highly treatable condition is warranted. The epidemiology, aetiology, clinical presentation, screening and management of Addison's disease ...

  5. Granulomatous cystitis in chronic granulomatous disease: Ultrasound diagnosis

    International Nuclear Information System (INIS)

    Hassel, D.R.; Glasier, C.M.; McConnell, J.R.; Arkansas Children's Hospital, Little Rock

    1987-01-01

    Chronic granulomatous disease (CGD) is a fatal hereditary disease of childhood characterized by chronic recurrent bacterial infections. Involvement of the genitourinary tract is uncommon. We report a child with CGD with granulomatous cystitis demonstrated by both ultrasound and computed tomography. (orig.)

  6. Somatic Diseases and Conditions Before the First Diagnosis of Schizophrenia

    DEFF Research Database (Denmark)

    Sørensen, Holger J; Nielsen, Philip Finn Rising; Benros, Michael E

    2015-01-01

    OBJECTIVE: Schizophrenia is associated with excess physical comorbidity. Yet, to our knowledge, large studies are lacking on the associations with somatic diseases before the onset of schizophrenia. The authors conducted a nationwide study of the full spectrum of treated somatic diseases before t...

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

    Directory of Open Access Journals (Sweden)

    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.

  8. Exome sequencing in a family segregating for celiac disease

    NARCIS (Netherlands)

    Szperl, A M; Ricaño-Ponce, I; Li, J K; Deelen, P; Kanterakis, A; Plagnol, V; van Dijk, Freerk; Westra, H J; Trynka, G; Mulder, C. J.; Swertz, M; Wijmenga, Cisca; Zheng, H C H

    Celiac disease is a multifactorial disorder caused by an unknown number of genetic factors interacting with an environmental factor. Hence, most patients are singletons and large families segregating with celiac disease are rare. We report on a three-generation family with six patients in which the

  9. [Enterovirus sequencing as a new approach to the laboratory diagnosis for clinical and epidemiological purposes].

    Science.gov (United States)

    Rainetová, P; Jiřincová, H; Musílek, M; Nováková, L; Vodičková, I; Štruncová, V; Švecová, M; Pazdiora, P; Piskunová, N; Trubač, P; Zajíc, T; Havlíčková, M

    2015-06-01

    Introducing enterovirus sequencing as an advanced approach to classify the viruses isolated according to the novel nomenclature and to characterize isolates in detail. Seventy-five specimens collected from 64 patients in two hospitals, Liberec Regional Hospital, and Plzeň University Hospital, were analyzed. The study patients' age ranged from four to 54 years, with a median of 15 years in males and 16 years in females. In most patients, the reasons for admission were intense headache, fever, vomiting, tiredness, meningeal symptoms, intestinal symptoms (in two patients), and skin symptoms (in one patient). The specimens collected were rectal and throat swabs, cerebrospinal fluid (CSF) and stool specimens. Molecular detection and typing were performed using the RT-PCR method. A segment of the 5´non-coding RNA was selected for typing. Specimens were amplified using single-step PCR with external primers and with the same primers extended to include M13 sequences (Generi-Biotech). The LASERGENE software (DIASTAR) was used in sequence editing, alignment, and quality check. The sequences obtained were checked against the central GenBank sequence database using the BLAST algorithm. The identification of the study isolates resulted in 61 ECHO viruses 30, three coxsackie viruses B1, one coxsackie virus B3, one coxsackie virus A9, one enterovirus 86, one enterovirus 71, Two ECHO viruses 13/coxsackie virus B5, one ECHO virus 7/30/coxsackie virus B4, one coxsackie virus B4/enterovirus B, one enterovirus 87/ECHO virus 30/enterovirus B, and one ECHO virus 3. All viruses isolated, except enterovirus 71 classified into group A, were of group B. The enteroviruses were identified unambigously, although the sequencing only targeted a short, conserved segment that showed considerable variability. The sequencing was an effective alternative to enterovirus identification by the neutralisation test and allowed for detailed characterization of the isolates. The predominance of ECHO 30 as

  10. 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

  11. 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.

  12. Mitochondrial DNA sequence variation in human evolution and disease.

    Science.gov (United States)

    Wallace, D C

    1994-09-13

    Germ-line and somatic mtDNA mutations are hypothesized to act together to shape our history and our health. Germ-line mtDNA mutations, both ancient and recent, have been associated with a variety of degenerative diseases. Mildly to moderately deleterious germ-line mutations, like neutral polymorphisms, have become established in the distant past through genetic drift but now may predispose certain individuals to late-onset degenerative diseases. As an example, a homoplasmic, Caucasian, tRNA(Gln) mutation at nucleotide pair (np) 4336 has been observed in 5% of Alzheimer disease and Parkinson disease patients and may contribute to the multifactorial etiology of these diseases. Moderately to severely deleterious germ-line mutations, on the other hand, appear repeatedly but are eliminated by selection. Hence, all extant mutations of this class are recent and associated with more devastating diseases of young adults and children. Representative of these mutations is a heteroplasmic mutation in MTND6 at np 14459 whose clinical presentations range from adult-onset blindness to pediatric dystonia and basal ganglial degeneration. To the inherited mutations are added somatic mtDNA mutations which accumulate in random arrays within stable tissues. These mutations provide a molecular clock that measures our age and may cause a progressive decline in tissue energy output that could precipitate the onset of degenerative diseases in individuals harboring inherited deleterious mutations.

  13. Fabry disease: recent advances in pathology, diagnosis, treatment and monitoring

    Directory of Open Access Journals (Sweden)

    Hoffmann Björn

    2009-10-01

    Full Text Available Abstract Background In Fabry disease (α-galactosidase A deficiency accumulation of Globotriaosylceramide (Gb3 leads to progressive organ failure and premature death. The introduction of enzyme replacement therapy (ERT was the beginning of a new era in this disorder, and has prompted a broad range of research activities. This review aims to summarize recent developments and progress with high impact for Fabry disease. Methods A Pubmed analysis was performed using the search terms "Fabry disease", "Anderson-Fabry disease", "alpha-galactosidase A" and "Gb3". Of the given publications by 31st January 2009 only original articles recently published in peer reviewed journals were included for this review. Case reports were included only when they comprised a new aspect. In addition we included relevant conference abstracts when the results had not already been published as original articles. Results Apart from Gb3-accumulation cellular and organ specific damages may be related also to inflammatory and immunological consequences. It will be interesting whether this may lead to new therapeutic strategies in the treatment of Fabry disease. Since newborn screening is still difficult in Fabry disease, detection of patients in populations at risk is of great importance. Undiagnosed patients with Fabry disease may still be found in cohorts of subjects with renal diseases, cardiomyopathy and TIA or stroke. Efforts should be undertaken to identify these individuals and initialise ERT in order to hault disease progression. It has also been demonstrated that Gb3-accumulation leads to pre-clinical damages and it is believed that early treatment may be the only possibility so far to prevent irreversible organ damage.

  14. New techniques in the tissue diagnosis of gastrointestinal neuromuscular diseases

    Institute of Scientific and Technical Information of China (English)

    Charles H Knowles; Joanne E Martin

    2009-01-01

    Gastrointestinal neuromuscular diseases are a clinically heterogeneous group of disorders of children and adults in which symptoms are presumed or proven to arise as a result of neuromuscular (including interstitial cell of Cajal) dysfunction. Common to most of these diseases are symptoms of impaired motor activity which manifest as slowed or obstructed transit with or without evidence of transient or persistent radiological visceral dilatation. A variety of histopathological techniques and allied investigations are being increasingly applied to tissue biopsies from such patients. This review outlines some of the more recent advances in this field, particularly in the most contentious area of small bowel disease manifesting as intestinal pseudo-obstruction.

  15. Expert System For Diagnosis Pest And Disease In Fruit Plants

    Science.gov (United States)

    Dewanto, Satrio; Lukas, Jonathan

    2014-03-01

    This paper discussed the development of an expert system to diagnose pests and diseases on fruit plants. Rule base method was used to store the knowledge from experts and literatures. Control technique using backward chain and started from the symptoms to get conclusions about the pests and diseases that occur. Development of the system has been performed using software Corvid Exsys developed by Exsys company. Results showed that the development of this expert system can be used to assist users in identifying the type of pests and diseases on fruit plants. Further development and possibility of using internet for this system are proposed.

  16. Validation of hospital register-based diagnosis of Parkinson's disease

    DEFF Research Database (Denmark)

    Wermuth, Lene; Lassen, Christina Funch; Himmerslev, Liselotte

    2012-01-01

    Denmark has a long-standing tradition of maintaining one of the world's largest health science specialized register data bases as the National Hospital Register (NHR). To estimate the prevalence and incidence of diseases, the correctness of the diagnoses recorded is critical. Parkinson's disease...... (PD) is a neurodegenerative disorder and only 75-80% of patients with parkinsonism will have idiopathic PD (iPD). It is necessary to follow patients in order to determine if some of them will develop other neurodegenerative diseases and a one-time-only diagnostic code for iPD reported in the register...

  17. 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...

  18. THE DIAGNOSIS AND CONTROL OF GAME DISEASES Division of ...

    African Journals Online (AJOL)

    dering infection of human Yellow fever in certain monkeys and bush-babies in Africa (Mc- ... in research work on the infectious diseases of game. .... The prophylactic vaccination of some of the animals in a park against the most important.

  19. Differential diagnosis of neurodegenerative diseases using structural MRI data

    DEFF Research Database (Denmark)

    Koikkalainen, Juha; Rhodius-Meester, Hanneke; Tolonen, Antti

    2016-01-01

    individuals was used for evaluation. The cross-validated classification accuracy was 70.6% and balanced accuracy was 69.1% for the five disease groups using only automatically determined MRI features. Vascular dementia patients could be detected with high sensitivity (96%) using features from FLAIR images....... Controls (sensitivity 82%) and Alzheimer's disease patients (sensitivity 74%) could be accurately classified using T1-based features, whereas the most difficult group was the dementia with Lewy bodies (sensitivity 32%). These results were notable better than the classification accuracies obtained...... characteristics from T1 images, and vascular characteristics from FLAIR images. Classification was performed using a multi-class classifier based on Disease State Index methodology. The classifier provided continuous probability indices for each disease to support clinical decision making. A dataset of 504...

  20. 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.)

  1. Diagnosis of diseases involving solid organs in the supramesocolic compartment

    Energy Technology Data Exchange (ETDEWEB)

    Herbreteau, D.; Solvit, D.; Anglade, M.C.; Mathieu, D.

    1989-04-01

    Sonographic and computed tomographic (CT) examinations have modified the investigation of hepatic, splenic and pancreatic tumors. Because of advances in non-invasive diagnostic procedures, these different benign or malignant tumors are now more frequently detected and surgically treated. However, for these different lesions sonography is the gold standard imaging technique. The different indications of CT and magnetic resonance imaging are discussed for each tumor. For the diagnostic imaging of an acutely injured patient, sonography remains the useful examination in emergencies. The indications of CT scans are limited to the difficulties of sonographic diagnosis in stable trauma patients.

  2. RNA Sequence of Spleen of Newcastle Disease Infected Chickens

    Data.gov (United States)

    US Agency for International Development — At 21 days of age, chickens were infected with Newcastle Disease virus (or a mock injection as controls), and spleens were harvested at 2 and 6 days post infection....

  3. CT in the diagnosis of coronary artery disease

    International Nuclear Information System (INIS)

    Shemesh, J.

    2005-01-01

    Atherothrombotic vascular disease remains the leading cause of mortality in the western countries. The underlying pathology is atherosclerosis, a systemic disease which affects the major organs, brain, kidney, and cardiovascular system. Despite the tremendous advances in the understanding of the atherosclerotic process, as well as in the development of the newest treatment modalities, the prevalence of atherosclerosis has not declined; neither has the incidence of cardiovascular morbidity and mortality. (orig.)

  4. [Diagnosis of a case with oculocutaneous albinism type Ⅲ with next generation exome capture sequencing].

    Science.gov (United States)

    Lyu, Yuqiang; Huang, Jing; Zhang, Kaihui; Liu, Guohua; Gao, Min; Gai, Zhongtao; Liu, Yi

    2017-02-10

    To explore the clinical and genetic features of a Chinese boy with oculocutaneous albinism. The clinical features of the patient were analyzed. The DNA of the patient and his parents was extracted and sequenced by next generation exome capture sequencing. The nature and impact of detected mutation were predicted and validated. The child has displayed strabismus, poor vision, nystagmus and brown hair. DNA sequencing showed that the patient has carried compound heterozygous mutations of the TYRP1 gene, namely c.1214C>A (p.T405N) and c.1333dupG, which were inherited from his mother and father, respectively. Neither mutation was reported previously. The child has suffered from oculocutaneous albinism type Ⅲ caused by mutations of the TYRP1 gene.

  5. 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.

  6. 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.

  7. Capsule endoscopy in the diagnosis of Crohn’s disease

    Directory of Open Access Journals (Sweden)

    Niv Y

    2013-05-01

    Full Text Available Yaron NivDepartment of Gastroenterology, Rabin Medical Center, Tel Aviv University, Petah Tikva, IsraelAbstract: Crohn’s disease is a chronic inflammatory disorder affecting any part of the gastrointestinal tract, but frequently involves the small and large bowel. Typical presenting symptoms include abdominal pain and diarrhea. Patients with this disorder may also have extraintestinal manifestations, including arthritis, uveitis, and skin lesions. The PillCam™SB capsule is an ingestible disposable video camera that transmits high quality images of the small intestinal mucosa. This enables the small intestine to be readily accessible to physicians investigating for the presence of small bowel disorders, such as Crohn’s disease. Four meta-analyses have demonstrated that capsule endoscopy identifies Crohn’s disease when other methods are not helpful. It should be noted that it is the best noninvasive procedure for assessing mucosal status, but is not superior to ileocolonoscopy, which remains the gold standard for assessment of ileocolonic disease. Mucosal healing along the small bowel can only be demonstrated by an endoscopic procedure such as capsule endoscopy. Achievement of long-term mucosal healing has been associated with a trend towards a decreased need for hospitalization and a decreased requirement for corticosteroid treatment in patients with Crohn’s disease. Recently, we have developed and validated the Capsule Endoscopy Crohn’s Disease Activity Index (also known as the Niv score for Crohn’s disease of the small bowel. The next step is to expand our score to the colon, and to determine the role and benefit of a capsule endoscopy activity score in patients suffering from Crohn’s ileocolitis and/or colitis. This scoring system will also serve to improve our understanding of the impact of capsule endoscopy, and therefore treatment, on the immediate outcome of this disorder. As the best procedure available for assessing

  8. 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

  9. 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

  10. Object analysis of bone marrow MR imaging using double echo STIR sequence in hematological diseases

    Energy Technology Data Exchange (ETDEWEB)

    Mizuno, Hitomi [Saitama Medical School, Moroyama (Japan)

    1995-07-01

    The bone marrow of 84 patients with hematological disorders was investigated using short inversion time inversion recovery sequence (STIR) on an 1.5 Tesla superconducting MRI system. Double echo times of 20 and 100 msec were applied to research the signal characteristics of the lesion and carry out quantitative analysis of the receiver operating characteristic curve (ROC). The hematological diseases included 19 cases of myelodysplastic syndrome (MDS), 18 of multiple myeloma (MM), 18 of chronic myelocytic leukemia (CML), 9 of aplastic anemia (AA), 8 of acute myelocytic leukemia (AML), 3 of chronic lymphocytic leukemia (CLL), 3 of myelofibrosis, and 3 others. Using STIR with double echo times, bone marrow showed high signal intensity (SI) on short TE and low SI on long TE in MDS and CML; high SI on short and long TE in myelofibrosis and CLL; high SI on short TE and high to moderately high SI on long TE in MM; and low SI on short and long TE in AA. Quantitative analysis of 33 patients showed high sensitivity and specificity in AA (81% and 94%, respectively) and moderate sensitivity and high specificity in MM (61%, 88%). CML and MDS were similar with low sensitivities (40%, 41%) and high specificities (80%, 78%). Differential diagnosis between CML and MDS was difficult using STIR with the double echo time method. (author).

  11. Left main coronary artery disease: pathophysiology, diagnosis, and treatment.

    Science.gov (United States)

    Collet, Carlos; Capodanno, Davide; Onuma, Yoshinobu; Banning, Adrian; Stone, Gregg W; Taggart, David P; Sabik, Joseph; Serruys, Patrick W

    2018-06-01

    The advent of coronary angiography in the 1960s allowed for the risk stratification of patients with stable angina. Patients with unprotected left main coronary artery disease have an increased risk of death related to the large amount of myocardium supplied by this vessel. Although coronary angiography remains the preferred imaging modality for the evaluation of left main coronary artery stenosis, this technique has important limitations. Angiograms of the left main coronary artery segment can be difficult to interpret, and almost one-third of patients can be misclassified when fractional flow reserve is used as the reference. In patients with clinically significant unprotected left main coronary artery disease, surgical revascularization was shown to improve survival compared with medical therapy and has been regarded as the treatment of choice for unprotected left main coronary artery disease. Two large-scale clinical trials published in 2016 support the usefulness of catheter-based revascularization in selected patients with unprotected left main coronary artery disease. In this Review, we describe the pathophysiology of unprotected left main coronary artery disease, discuss diagnostic approaches in light of new noninvasive and invasive imaging techniques, and detail risk stratification models to aid the Heart Team in the decision-making process for determining the best revascularization strategy for these patients.

  12. Diagnosis of Fatal Human Case of St. Louis Encephalitis Virus Infection by Metagenomic Sequencing, California, 2016.

    Science.gov (United States)

    Chiu, Charles Y; Coffey, Lark L; Murkey, Jamie; Symmes, Kelly; Sample, Hannah A; Wilson, Michael R; Naccache, Samia N; Arevalo, Shaun; Somasekar, Sneha; Federman, Scot; Stryke, Doug; Vespa, Paul; Schiller, Gary; Messenger, Sharon; Humphries, Romney; Miller, Steve; Klausner, Jeffrey D

    2017-10-01

    We used unbiased metagenomic next-generation sequencing to diagnose a fatal case of meningoencephalitis caused by St. Louis encephalitis virus in a patient from California in September 2016. This case is associated with the recent 2015-2016 reemergence of this virus in the southwestern United States.

  13. [Diagnosis and insurance compensation of occupational diseases in construction industry].

    Science.gov (United States)

    Bresciani, M; Riva, M M; Giorgi, M; Ghezzi, L; Sidoti, C; Mosconi, G

    2007-01-01

    The aim of this study is to evaluate the outcome of 302 occupational diseases in building workers detected by UOOML Ospedali Riuniti of Bergamo and notified to INAIL from 2000 to 2005. The 41.3% of cases were accepted as work-related. Among remaining cases (58.7%), INAIL rejected 40.9% for lack or absence of documentation. 59.1% for no adhesion to legal medicine criteria. By analysis of occupational diseases detected in the last 5 years, we found an increase of muscle-skeletal disorders, for which, now, diagnostic procedure and insurance evaluation are difficult. This work shows a wide gap between reported occupational diseases of buildings workers and compensation given by INAIL. These results underlines the need of comparison among involved institutions in order to standardize statistical and diagnostic instruments.

  14. Leprosy, a Pleitropic infectious disease: a challenging diagnosis

    Directory of Open Access Journals (Sweden)

    Manal El Meniawy

    2018-01-01

    Full Text Available This is a case report of 22-year-old man who was suffering from epididymo-orchitis for more than 2 years. Several months after the onset of the condition, the patient developed bilateral upper-limb and lower-limb numbness and tingling sensation with hypothesia, which was further complicated by nonhealing foot ulcer, arthralgia, and generalized maculopapular skin rash. The patient was initially managed as rheumatoid arthritis associated with vasculitis, which was later diagnosed as lepromatous leprosy. Musculoskeletal complaints are not exclusive to only autoimmune diseases; it can also be observed in several disorders, such as infectious diseases. It is challenging for any physician to properly diagnose patients with leprosy as differentiating leprosy from other systemic rheumatic disease is pivotal.

  15. Extraintestinal manifestations of inflammatory bowel disease: epidemiology, diagnosis, and management

    DEFF Research Database (Denmark)

    Larsen, Signe; Bendtzen, Klaus; Nielsen, Ole Haagen

    2010-01-01

    Abstract Extraintestinal manifestations occur rather frequently in inflammatory bowel disease (IBD), e.g. ulcerative colitis (UC) and Crohn's disease (CD). The present paper provides an overview of the epidemiology, clinical characteristics, diagnostic process, and management of rheumatic......, metabolic, dermatologic (mucocutaneous), ophthalmologic, hepatobiliary, hematologic, thromboembolic, urinary tract, pulmonary, and pancreatic extraintestinal manifestations related to IBD. Articles were identified through search of the PubMed and Embase databases, the Cochrane Library, and the web sites......', 'thromboembolism', and 'treatment'. The search was performed on English-language reviews, practical guidelines, letters, and editorials. Articles were selected based on their relevance, and additional papers were retrieved from their reference lists. Since some of the diseases discussed are uncommon, valid...

  16. Value of computed tomography in diagnosis of intestinal diseases

    International Nuclear Information System (INIS)

    Fujikawa, Koichi; Yamane, Kosuke; Nakanishi, Tadashi; Miura, Yoshio; Kato, Yoshitaka; Yahata, Noriko; Iwamoto, Toshiyuki; Katayama, Hiroshi; Katsuta, Shizutomo.

    1987-01-01

    CT findings of 46 cases with inflammatory and other nontumoral bowel diseases were retrospectively studied. Patients were given 500 to 1000 ml of lukewarm water orally or rectally to distend the intestinal lumen. In all cases water-soluble iodine contrast media was administered intravenously. The CT findings in Crohn's disease included mural thickening, luminal narrowing, bowel wall enhancement, wall rigidity, serration of intestinal border, dilatation of mesenteric vessels, periintestinal blurring (inflamatory reaction of mesentery), fibrofatty proliferation, effusion, abscess and fistula. Many of these findings suggested the transmural nature of the disease and gave diagnostic clues of the disease. In cases with ulcerative colitis, thickening of bowel wall was insignificant and extraintestinal complications were absent. CT appears to play an important role in distinguishing Crohn's disease and ulcerative colitis. Luminal narrowing and mural thickening were also observed in a case with intestinal ischemia, but these mural changes were not accompanied by mesenteric abnormalities to the degree of Crohn's disease. In cases with penetrating peptic ulcer and diverticulitis, CT demonstrated inflammatory reactions of surrounding tissue such as thickening of neighboring fascia, increase in attenuation value of mesenteric fat, effusion and abscess. Even in cases with confusing clinical symptoms, appendicitis was easily diagnosed on CT which showed swelling of appendix and inflammatory changes of surrounding structures. Mechanical obstruction of the intestine could be identified on CT by a notable change of luminal sizes at the site of obstruction. CT appearances of intussusception were distinctive and a soft tissue mass (intussusceptum) and mesenteric fat was seen within a markedly dilated intussuscipiens. CT could also reveal pancreatitis and splenic infarction as the causes of clinically-undiagnosed paralytic ileus. (J.P.N.)

  17. Significance of computed tomography for diagnosis of heart diseases

    International Nuclear Information System (INIS)

    Senda, Kohei; Sakuma, Sadayuki

    1983-01-01

    Computed tomography (CT) with a 2 sec scanner was carried out on 105 cases with various heart disease in order to detect CT findings in each heart disease. Significance of CT as a imaging study was evaluated in comparison with scintigraphic, echographic and roentgenographic studies. CT with contrast enhancement in moderate inspiration was able to demonstrate accurately organic changes of intra-and extracardiac structure. Comparing with other imaging studies, CT was superior in detection of calcified or intracardiac mass lesion in spite of low value in evaluating cardiac function or dynamics. (author)

  18. Computed tomography in the diagnosis of Addison's disease

    International Nuclear Information System (INIS)

    Yamauchi, Teiyu; Yashiro, Naofumi; Iio, Masahiro

    1985-01-01

    The computed tomography (CT) findings of the adrenal glands were described in six patients with Addison's disease. Three of four patients due to tuberculosis showed calcification in bilateral adrenal glands. In all three, non-calcified portions of left adrenal glands were identified by CT. One showed bilaterally enlarged adrenal glands. Bilateral adrenal glands were small in a patient with idiopatic Addison's disease. One patient of metastatic infiltration of the adrenal glands showed nodular masses in bilateral adrenal beds. CT findings were useful to clarify the etiology of Addison's patients. (author)

  19. Potential of radiocopper in the diagnosis of Wilson disease

    International Nuclear Information System (INIS)

    Archambaud, F.; Yvart, J.; Moati, F.; Bernard, O.; Dommergues, J.P.; Desgrez, A.; Odievre, M.

    1988-01-01

    The purpose of the study is to establish if a simple test with 64 Cu is a valuable means of differenciating homozygotes for the ''Wilson's disease gene'' from heterozygous carriers and normal subjects for copper metabolism. A group of 73 subjects were studied. The only parameter which appears to be interesting is the percentage of administrated 64 Cu incorporated into ceruloplasmin at 48h. This test appears to be interesting to predict the disease and to avoid biopsy for determination of hepatic copper concentration [fr

  20. Radiosensitivity in Huntington's disease: implications for pathogenesis and presymptomatic diagnosis

    International Nuclear Information System (INIS)

    Moshell, A.N.; Tarone, R.E.; Barrett, S.F.; Robbins, J.H.

    1980-01-01

    Huntington's disease (HD) is a dominantly inherited fatal disorder characterised by premature death of nerve cells. Cultured lymphocyte lines from four patients with HD were abnormally sensitive to the lethal effects of X rays, as were lines from two of five subjects at risk for HD. The hypersensitivity is specific for ionising radiation, since HD lines had normal survival after exposure to ultraviolet radiation. The hypersensitivity, which may reflect an inherited defect in DNA repair, provides the basis for a presymptomatic diagnostic test for the disease. (author)

  1. Problems associated with the diagnosis and treatment of endodontic disease

    International Nuclear Information System (INIS)

    Emily, P.

    1990-01-01

    The diagnosis of endodontic lesions in animal dentistry is complicated and restricted by the use of objective diagnostic procedures. Human endodontics uses subjective symptoms to a large degree, as well as objective symptoms. Subjective symptoms include patient pain; sensitivity to hot or cold; percussion; and foul taste or odor. Veterinary dentists must receive input from clients, as well as using their own clinical and radiographic evaluation. Many endodontic lesions remain undetected because the client fails to notice broken or discolored teeth, facial swelling, drooling, difficulty in chewing, chewing only on one side, and general malaise. An increased awareness of the endodontic problems that can occur in animals increases the level of veterinary care. Numerous techniques, including apexogenesis, apexification, direct and indirect pulp capping, and conventional and surgical endodontic therapy, can be used to treat various endodontic problems successfully

  2. Pneumonia: challenges in the definition, diagnosis, and management of disease.

    Science.gov (United States)

    Ottosen, Julie; Evans, Heather

    2014-12-01

    Defining health care-associated pneumonia, which includes both hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP), is problematic and controversial. Aspiration pneumonia is often included as a subtype of HAP but may be related to community-acquired aspiration events. Scoring systems exist and new surveillance guidelines have been implemented to make early recognition of pneumonia more precise and objective. Management and prevention should follow recommendations, including early empirical therapy, targeted therapy, and limited duration of treatment. Patients with trauma present a challenge to the diagnosis and management of pneumonia, because of increased risk for aspiration and underlying chest and pulmonary injury. Copyright © 2014 Elsevier Inc. All rights reserved.

  3. Osteomesopyknosis associated to renal lithiasis. Case report. Differential diagnosis of the axial osteoesclerosant diseases

    International Nuclear Information System (INIS)

    Quintana, Gerardo; Fernandez, Andres; Restrepo, Jose Felix; Rojas, Adriana; Calvo, Enrique; Rondon, Federico; Sanchez, Alvaro; Forero, Elias; Iglesias, Antonio

    2004-01-01

    In this article we present a brief description of the bone diseases characterized by osteosclerosis. We present our experience with their morpho-radiological changes, we describe a case of osteomesopyknosis associated to renal lithiasis and we propose a classification for osteosclerosant diseases of the axial skeleton with practical differential diagnosis of these conditions

  4. Updated German S3-guideline regarding the diagnosis of Crohn's disease. Implementation of radiological modalities

    International Nuclear Information System (INIS)

    Schreyer, A.G.; Ludwig, D.; Koletzko, S.; Hoffmann, J.C.; Preiss, J.C.; Zeitz, M.; Stange, E.; Herrlinger, K.R.

    2010-01-01

    The recently updated German S3-guideline regarding the diagnosis and treatment of Crohn's disease incorporates several changes concerning the radiological approach compared to the former guideline. This article focuses on guideline-based radiological imaging techniques for patients with Crohn's disease. The new guideline is also compared to former European and German guidelines in the context of recently published radiological literature. (orig.)

  5. 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)

  6. 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...

  7. Global Strategy for the Diagnosis, Management and Prevention of Chronic Obstructive Pulmonary Disease, GOLD Executive Summary

    DEFF Research Database (Denmark)

    Vestbo, Jørgen; Hurd, Suzanne S; Agusti, Alvar G

    2013-01-01

    Chronic obstructive pulmonary disease (COPD) is a global health problem and since 2001 the Global Initiative for Chronic Obstructive Lung Disease (GOLD) has published its strategy document for the diagnosis and management of COPD. This executive summary presents the main contents of the second 5...

  8. 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.

  9. Rare disease diagnosis as an information retrieval task

    DEFF Research Database (Denmark)

    Dragusin, Radu; Petcu, Paula; Lioma, Christina

    2011-01-01

    Increasingly more clinicians use web Information Retrieval (IR) systems to assist them in diagnosing difficult medical cases, for instance rare diseases that they may not be familiar with. However, web IR systems are not necessarily optimised for this task. For instance, clinicians’ queries tend...

  10. X-ray diagnosis of diseases of operated stomach

    International Nuclear Information System (INIS)

    Petrova, I.S.; Rozenfel'd, L.G.; Ostapenko, T.A.; Shpontak, A.S.

    1985-01-01

    Principal methods for operations on the stomach, X-ray examinations of patients with the operated stomach are described as well as the state of the stomach after different surgical treatments. Radiodiagnosis of operated stomach complications in early and late postoperative periods, diseases of the operated stomach, cancer relapse after an operation, dumping syndrome, are considered

  11. Non-Motor Symptoms of Parkinson's Disease: Diagnosis and ...

    African Journals Online (AJOL)

    Non-motor symptoms (NMS) of Parkinson's disease (PD) are a key determinant of health, quality of life (QoL) and societal cost of PD. They are often less appreciated than motor symptoms but are important sources of disability for manyPDpatients. Literature search was performed using the reference databases Medline, ...

  12. Diagnosis of cardiovascular diseases by digital fluoroscopic angiography

    International Nuclear Information System (INIS)

    Takahashi, Mutsumasa; Hirota, Yoshihisa; Tsuchigame, Naotoshi

    1982-01-01

    Digital fluoroscopic angiography (DFA) is a recently developed angiocardiographic technique, which consists of digitization and real-time subtraction of X-ray transmission data from an image intensifier and television fluoroscopic system. A prototype unit based on this principle was developed and installed at our hospital and initial clinical trial has been performed. Fifty-three examinations were performed on 49 patients with various cardiovascular conditions. DFA was useful in demonstration of intracardiac shunt, and valvular diseases secondary to congenital heart diseases. In ischemic heart diseases, DFA noninvasively demonstrated the heart wall motion, making it possible to evaluate dyskinesis, akinesis and ventricular aneurysm. DFA was also valuable in visualizing disproportionate enlargement of cardiac chambers, stasis, and frequently regurgitation of contrast media in valvular heart diseases. Abnormal mediastinal enlargement and aortic aneurysm were differentiated from other conditions to good advantage. DFA will be used more widely in the above conditions because of non-invasive and simple procedures. Future effort should be directed towards improvement of spatial resolution and development of new algorithm for hemodynamic evaluation. (author)

  13. Non-Motor Symptoms of Parkinson's Disease: Diagnosis and ...

    African Journals Online (AJOL)

    AFRICAN JOURNALS ONLINE (AJOL) · Journals · Advanced Search · USING AJOL · RESOURCES ... Log in or Register to get access to full text downloads. ... Abstract. Non-motor symptoms (NMS) of Parkinson's disease (PD) are a key ... Papers discovered by this search were. reviewed, as were references cited therein.

  14. Erroneous diagnosis of gastroesophageal reflux disease in achalasia

    NARCIS (Netherlands)

    Kessing, Boudewijn F.; Bredenoord, Albert J.; Smout, André J. P. M.

    2011-01-01

    Most experienced gastroenterologists have seen one or several cases of achalasia patients who have been erroneously diagnosed with gastroesophageal reflux disease (GERD) or even underwent antireflux surgery. We aim to describe the current knowledge about the diagnostic features of achalasia and

  15. Pattern and Diagnosis of Congenital Heart Disease in Patients ...

    African Journals Online (AJOL)

    Objective: To study the pattern of Congenital Heart Diseases (CHD) in children referred to Ahmed Gasim Cardiac Center) in Khartoum. Methods: This is a prospective cross-sectional, clinic based study conducted over a six months period. The children were referred to the Cardiac Centre because of suspected heart ...

  16. Diagnosis of alcohol misuse and alcoholic liver disease among ...

    African Journals Online (AJOL)

    Alcohol related hepatocellular liver injury was assessed using aspartate aminotransferase, and alanine aminotransferase levels. A combination of CAGE score ≥2 and De Ritis ratio ≥2 defined alcoholic liver disease (ALD). Human Immunodeficiency Virus (HIV), and viral hepatitis B and C serologies were evaluated in all ...

  17. Micro PIXE investigations. Time sequencing studies in degenerative diseases

    International Nuclear Information System (INIS)

    Watt, F.; Minqin, R.; Patricia Thong ps

    1999-01-01

    The simultaneously applied techniques of Particle Induced X-ray Emission (PIXE), Rutherford Backscattering Spectrometry (RBS) and Scanning Transmission Ion Microscopy (STIM), have been successful in mapping and quantifying trace elements during the progression of several human diseases, in particular those degenerative diseases which have a corresponding animal model. In atherosclerosis, iron has been shown to be present in increased concentrations at the early stage of lesion formation, and when the animal model has been kept anaemic, the artery wall shows a reduced uptake of iron and a delay in lesion formation compared with controls. In Parkinson's disease, there is also an increased concentration of iron in the substantia nigra region of the brain. Although the increase in bulk iron appears to lag behind the dopaminergic cell death, we have detected an increase in localized deposits of iron at the onset of cell death. These two results infer that iron may play a role in both diseases, perhaps through the mediation of free radicals. The induction of epilepsy through the injection of kainic acid has shown that the cell death is accompanied by an increase in calcium levels as early as one day after injection. The increase in calcium is consistent with activation of phospholipase A 2 and free radical damage. (author)

  18. 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.)

  19. 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)

  20. 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.

  1. 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.

  2. 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

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

    Science.gov (United States)

    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.

  4. 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.

  5. 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.

  6. Targeted massively parallel sequencing and histological assessment of skeletal muscles for the molecular diagnosis of inherited muscle disorders.

    Science.gov (United States)

    Nishikawa, Atsuko; Mitsuhashi, Satomi; Miyata, Naomasa; Nishino, Ichizo

    2017-02-01

    Inherited skeletal muscle diseases are genetically heterogeneous diseases caused by mutations in more than 150 genes. This has made it challenging to establish a high-throughput screening method for identifying causative gene mutations in clinical practice. In the present study, we developed a useful method for screening gene mutations associated with the pathogenesis of skeletal muscle diseases. We established four target gene panels, each covering all exonic and flanking regions of genes involved in the pathogenesis of the following muscle diseases: (1) muscular dystrophy (MD), (2) congenital myopathy/congenital myasthenic syndrome, (3) metabolic myopathy and (4) myopathy with protein aggregations/rimmed vacuoles. We assigned one panel to each patient based on the results of clinical and histological analyses of biopsied muscle samples and performed high-throughput sequencing by using Ion PGM next-generation sequencer. We also performed protein analysis to confirm defective proteins in patients with major muscular dystrophies. Further, we performed muscle-derived cDNA analysis to identify splice-site mutations. We identified possible causative gene mutations in 33% of patients (62/188) included in this study. Our results showed that the MD panel was the most useful, with a diagnostic rate of 46.2%. Thus, we developed a high-throughput sequencing technique for diagnosing inherited muscle diseases. The use of this technique along with histological and protein analyses may be useful and cost-effective for screening mutations in patients with inherited skeletal muscle diseases. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  7. New developments in foot-and-mouth disease diagnosis

    International Nuclear Information System (INIS)

    Kitching, R.P.; MacKay, D.K.J.

    1998-01-01

    A variety of newer diagnostic procedures based around the use of molecular technologies are now being undertaken to further characterise the foot-and-mouth disease (FMD) virus enabling a deeper understanding to be gained of the pathogenesis and epidemiology of this disease. Such approaches have categorically identified the carrier state and highlighted the importance of carrier animals in control programmes. Use of the polymerase chain reaction provides even further insight into the carrier animal but interpretation of data has to be undertaken with caution. The role of non-structural proteins can provide further insight into an animals response to both vaccination and natural infection and could provide a basis for separation of the carrier state. Finally the pivotal role of monoclonal antibodies in all aspects of FMD research is now clear and these highly specific reagents are now being used for a variety of research and diagnostic purposes within the FMD field. (author)

  8. [Diagnosis and therapy of particle disease in total hip arthroplasty].

    Science.gov (United States)

    Müller, M; Wassilew, G; Perka, C

    2015-04-01

    Particle disease is caused by periarticular accumulation of attrition particles and the inflammatory reaction of the body's tissue. This process may result in osteolysis or soft tissue transformation which presents itself symptomless in the beginning and can proceed to aseptic implant loosening, fracture, implant breaking as a result of the inappropriate osseous support and to algetic and destructive soft tissue reactions as well. Attrition particles originate from tribological pairing, and the extent of the attrition or the particle concentration depend on different factors as there are the tribological pairing's material, the head size, the patient's level of activity, and the implant position. Attrition particles can also be found in the range of any modular connection. Particle disease and its resulting morphological alterations of the tribological pairing is one of the most frequent reasons for re-operation in hip endoprosthetics. Georg Thieme Verlag KG Stuttgart · New York.

  9. Diagnosis of thyroid disease. Anamnesis and physical examination

    International Nuclear Information System (INIS)

    Freudenberg, L.S.

    2008-01-01

    Anamnesis and physical examination rank first in the diagnostic process of thyroid disease. They provide a basis for subsequent diagnostic procedures and treatment. This article focusses on personal, medical and familial history as well as physical examination of the neck and general clinical examination with respect to signs and symptoms of hypo- or hyperthyreoidism. In addition indications for fine-needle biopsy and biopsy technique are described. (orig.)

  10. Alzheimer disease: diagnosis, costs, and dimensions of treatment.

    Science.gov (United States)

    DeKosky, S T; Orgogozo, J M

    2001-08-01

    Alzheimer disease (AD) is the most frequent cause of dementia in developed Western countries. Over time, affected patients invariably develop cognitive and functional decline, and most develop early or later behavioral disturbances. Declining cognitive and functional abilities contribute to loss of independent living and feelings of denial, confusion, fear and guilt until, finally, the patient loses most abilities to think, move, speak, or perceive. As patients' dependency on assistance increases, the level of caregiver strain rises. The caregiver may develop feelings of anger, grief, loneliness and resentment, and the health and well-being of most caregivers are often affected. Approximately 3-4 million people currently have AD in the USA, at an annual cost of up to US$100 billion, and the disease is expected to reach epidemic proportions by 2020. To achieve a clinically relevant, long-term outcome, pharmacotherapy must have sustained favorable effects on cognitive, functional and behavioral symptoms of AD. Slowing the development of these features of the disease will mean a long-term improvement in quality of life for patients and caregivers. Postponing the emergence of behavioral symptoms would bring about direct beneficial effects on patients with AD and their families, help delay long-term care placement and lower costs.

  11. Evaluation of pancreatic scintigram in the diagnosis of pancreatic diseases

    International Nuclear Information System (INIS)

    Takai, Yukihiro; Ueda, Noriyuki; Takasago, Noritsugu; Minemoto, Hiromasa; Namiki, Masayoshi

    1981-01-01

    The classification of accumulative patterns with the pancreatic scintigram findings of chronic pancreatitis and carcinoma of the pancreas were compared with endoscopic retrograde pancreatography (ERP) findings and Pancreozymin-Secretin test (P-S test). I) The frequency of pancreatic cancer was 93%, whilst, the chronic pancreatitis was 88% in the abnormal pancreatic scintigram. II) In the scintigram the type II (localyzed defect shadows) of pancreatic cancer was comparatively high and it is proportional to evidence. derived from ERP. Localized diagnostic certainty is helpful, although the two tests are related. The P-S test is only restricted to the carcinoma of head, whilst, scintigram is more useful to detect the carcinoma of the body and tail of the pancreas. III) As for the chronic pancreatitis, there are various accumulative patterns. This is resemblance to that of ERP findings, but in the P-S normal test, it showed discrepancy in part of the result. Particularly, in the type I (slightly generalized low uptake with density silhouette) and type II. Therefore in order to obtain an accurate diagnosis, it is essential to have both the P-S test and scintigram. (author)

  12. Multifunctional gold nanoparticles for diagnosis and therapy of disease

    Science.gov (United States)

    Mieszawska, Aneta J.; Mulder, Willem J. M.; Fayad, Zahi A.

    2013-01-01

    Gold nanoparticles (AuNPs) have a number of physical properties that make them appealing for medical applications. For example, the attenuation of X-rays by gold nanoparticles has led to their use in computed tomography imaging and as adjuvants for radiotherapy. AuNPs have numerous other applications in imaging, therapy and diagnostic systems. The advanced state of synthetic chemistry of gold nanoparticles offers precise control over physicochemical and optical properties. Furthermore gold cores are inert and are considered to be biocompatible and non-toxic. The surface of gold nanoparticles can easily be modified for a specific application and ligands for targeting, drugs or biocompatible coatings can be introduced. AuNPs can be incorporated into larger structures such as polymeric nanoparticles or liposomes that deliver large payloads for enhanced diagnostic applications, efficiently encapsulate drugs for concurrent therapy or add additional imaging labels. This array of features has led to the afore-mentioned applications in biomedical fields, but more recently in approaches where multifunctional gold nanoparticles are used for multiple methods, such as concurrent diagnosis and therapy, so called theranostics. The following review covers basic principles and recent findings in gold nanoparticle applications for imaging, therapy and diagnostics, with a focus on reports of multifunctional AuNPs. PMID:23360440

  13. 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.

  14. Comparison of two next-generation sequencing kits for diagnosis of epileptic disorders with a user-friendly tool for displaying gene coverage, DeCovA

    Directory of Open Access Journals (Sweden)

    Sarra Dimassi

    2015-12-01

    Full Text Available In recent years, molecular genetics has been playing an increasing role in the diagnostic process of monogenic epilepsies. Knowing the genetic basis of one patient's epilepsy provides accurate genetic counseling and may guide therapeutic options. Genetic diagnosis of epilepsy syndromes has long been based on Sanger sequencing and search for large rearrangements using MLPA or DNA arrays (array-CGH or SNP-array. Recently, next-generation sequencing (NGS was demonstrated to be a powerful approach to overcome the wide clinical and genetic heterogeneity of epileptic disorders. Coverage is critical for assessing the quality and accuracy of results from NGS. However, it is often a difficult parameter to display in practice. The aim of the study was to compare two library-building methods (Haloplex, Agilent and SeqCap EZ, Roche for a targeted panel of 41 genes causing monogenic epileptic disorders. We included 24 patients, 20 of whom had known disease-causing mutations. For each patient both libraries were built in parallel and sequenced on an Ion Torrent Personal Genome Machine (PGM. To compare coverage and depth, we developed a simple homemade tool, named DeCovA (Depth and Coverage Analysis. DeCovA displays the sequencing depth of each base and the coverage of target genes for each genomic position. The fraction of each gene covered at different thresholds could be easily estimated. None of the two methods used, namely NextGene and Ion Reporter, were able to identify all the known mutations/CNVs displayed by the 20 patients. Variant detection rate was globally similar for the two techniques and DeCovA showed that failure to detect a mutation was mainly related to insufficient coverage.

  15. Diagnosis and Treatment of IgG4-Related Disease.

    Science.gov (United States)

    Kamisawa, Terumi; Okazaki, Kazuichi

    2017-01-01

    It is critical to differentiate IgG4-related disease (IgG4-RD) from malignant tumor and similar disease of the affected organ to apply appropriate therapy and avoid unnecessary surgery. IgG4-RD is diagnosed on combination of typical radiological findings; elevation of serum IgG4 levels; histopathological findings of abundant infiltration of IgG4-positive plasma cells and lymphocytes, storiform fibrosis , and obliterative phlebitis ; association with other IgG4-related diseases; and response to steroids. Histopathological approach is particularly recommended. Systemic glucocorticoids are currently the first-line approach for IgG4-RD, and the indications are symptoms. The initial recommended dose of oral prednisolone for induction of remission is 0.6 mg/kg/day, administered for 2-4 weeks. This dose is gradually tapered to a maintenance dose of 2.5-5 mg/day over a period of 2-3 months. As IgG4-RD sometimes relapses after steroids, maintenance therapy is usually performed in Japan. However, as IgG4-RD patients are typically elderly and are at high risk of developing steroid-related complications, cessation of the medication should be attempted at least within 3 years. For relapsed IgG4-RD, re-administration or dose up of steroid is effective, but the addition of immunomodulatory drugs such as azathioprine has been considered to be appropriate. B cell depletion with rituximab (an anti-CD20 antibody) is effective, even in many patients in whom treatment with immunomodulatory drugs was unsuccessful. The short-term clinical, morphological, and functional outcomes of most IgG4-RD patients treated with steroid therapy are good, but the long-term outcomes are less clear due to several unknown factors such as relapse, developed fibrosis, and associated malignancy.

  16. Accuracy of nursing diagnosis "readiness for enhanced hope" in patients with chronic kidney disease.

    Science.gov (United States)

    Silva, Renan Alves; Melo, Geórgia Alcântara Alencar; Caetano, Joselany Áfio; Lopes, Marcos Venícios Oliveira; Butcher, Howard Karl; Silva, Viviane Martins da

    2017-07-06

    To analyse the accuracy of the nursing diagnosis readiness for enhanced hope in patients with chronic kidney disease. This is a cross-sectional study with 62 patients in the haemodialysis clinic conducted from August to November 2015. The Hearth Hope Scale was used to create definitions of the defining characteristics of the North American Nursing Diagnosis Association International. We analysed the measures of sensitivity, specificity, predictive value, likelihood ratio, and odds ratio of the defining characteristics of the diagnosis. Of the characteristics, 82.22% presented the diagnosis. The defining characteristics "Expresses the desire to enhance congruency of expectations with desires" and "Expresses the desire to enhance problem solving to meet goals" increased the chance of having the diagnosis by eleven and five, respectively. The characteristics, "Expresses desire to enhance congruency of expectations with desires" and "Expresses desire to enhance problem solving to meet goals" had good accuracy measures.

  17. Refinement of gamma-camera diagnosis of cardiovascular diseases

    International Nuclear Information System (INIS)

    Shejretova, E.; Garcheva, M.; Trindev, P.; Hadzhikostova, H.

    1989-01-01

    The following new methods of radionuclide diagnostic techniques were introduced: 1. Study of regional myocardial perfusion: a) Late (on hour 18) follow-up of the redistribution of 201 Tl images in the heart muscle; b) background correction and computer processing of early and late 201 Tl images in the heart muscle. 2. Study of the pump cardiac function: a) program for manual outlining of left ventricular contours; b) phase analysis; c) method for objective differention of the reight ventricle. The methods described have been used in 210 patients with cardiovascular diseases

  18. Marine disease impacts, diagnosis, forecasting, management and policy

    Science.gov (United States)

    Lafferty, Kevin D.; Hofmann, Eileen E.

    2016-01-01

    As Australians were spending millions of dollars in 2014 to remove the coral-eating crown of thorns sea star from the Great Barrier Reef, sea stars started washing up dead for free along North America's Pacific Coast. Because North American sea stars are important and iconic predators in marine communities, locals and marine scientists alike were alarmed by what proved to be the world's most widespread marine mass mortality in geographical extent and species affected, especially given its mysterious cause. Investigative research using modern diagnostic techniques implicated a never-before-seen virus [1]. The virus inspired international attention to marine diseases, including this theme issue.

  19. Diagnosis of hoof diseases in horses using computed tomography

    International Nuclear Information System (INIS)

    Kovac, M.; Nowak, M.; Kaufels, N.; Tambur, Z.

    2002-01-01

    This study describes findings of computed tomography investigations at the Bergische Equine Clinic (Bergische Tierklinik), Germany, of 39 horses with hoof diseases. The most frequently findings were the navicular syndrome (eight horses), laminitis (seven horses), keratnoma (six horses) and ossification of collateral cartilages in the distal phalanx (four horses). The special value of the computed tomography is in evaluating the size and courses fracture/fissure of the navicular and koffin bones, which were diagnose in five horses. In four of horses no pathologic changes of the hoof were determined by computed tomography

  20. The advancement in Alzheimer disease of imaging diagnosis

    International Nuclear Information System (INIS)

    Wang Xinyan; Guan Yihui

    2013-01-01

    Alzheimer disease (AD) is one of the neurodegenerative disorders that deteriorate the life quality of the elderly in China and developed countries. Prevention and treatment of AD are the focal point in the study of brain science. In recent years,the rapid development of medical imaging technology enables us to get functional orientation and structure description of brain noninvasively and provides a substantial basis for studies of cognition, cognitive impairment, and pathogenesis.It also makes such multi-tiered research and trans-subject combination possible. The progress in AD of imaging technology is briefly reviewed in this article. (authors)

  1. Diagnosis application of ACTH radioimmunoassay in diseases of hypothalamus, hypophysis and adrenal axis

    International Nuclear Information System (INIS)

    Moreira, A.C.; Foss, M.C.; Iazigi, N.

    1988-01-01

    The diagnostic value of 900-1,100 am plasma ACTH radioimmunoassay were studied in 10 patients with Cushing's disease before and after treatment, three patients with Cushing's syndrome with adrenal tumours, one Nelson's syndrome patient; 13 patients with Addison's disease and 12 patients with hypo-pituitarism. Twenty-seven normal subjects were controls. The measurement of basal plasma ACTH gave good differentiation between: a. pituitary Cushing's disease from adrenal tumors; b. Addison's disease from hypo-pituitarism. However this assay has a limited value for the differentiation between Cushing's disease from normal subjects and it is often unhelpful in the differential diagnosis of hypo-pituitarism from normal subjects. (author)

  2. Early chronic kidney disease: diagnosis, management and models of care

    Science.gov (United States)

    Wouters, Olivier J.; O'Donoghue, Donal J.; Ritchie, James; Kanavos, Panos G.; Narva, Andrew S.

    2015-01-01

    Chronic kidney disease (CKD) is a prevalent condition in many countries, and it is estimated that over $1 trillion is spent globally on end-stage renal disease (ESRD) care. There is a clear clinical and economic rationale for designing timely and appropriate health system responses to limit progression from CKD to ESRD. This article reviews the gaps in our knowledge about which early CKD interventions are appropriate, the optimal time to intervene, and what model of care to adopt. The available diagnostic tests exhibit key limitations. Clinical care may improve if early-stage (1–3) CKD with risk for progression towards ESRD is differentiated from early CKD that is unlikely to advance. It is possible that CKD should be re-conceptualized as a part of primary care. Additional research is needed to better understand the risk factors for CKD progression. Systems modelling can be used to evaluate the impact of different care models on CKD outcomes and costs. The US Indian Health Service experience has demonstrated that an integrated, system-wide approach, even in an underfunded system, can produce significant benefits. PMID:26055354

  3. [Dysphagia in Parkinson's Disease: Pathophysiology, Diagnosis and Therapy].

    Science.gov (United States)

    Suttrup, I; Warnecke, T

    2016-07-01

    Oropharyngeal and esophageal dysphagia are a frequent, but seldom diagnosed symptom of Parkinson's disease (PD). More than 80 % of patients with PD develop dysphagia during the course of their disease leading to a reduced quality of life, complicated medication intake, malnutrition and aspiration pneumonia, which is a major cause of death in PD. The underlying pathophysiology is poorly understood. Impaired dopaminergic and non-dopaminergic mechanisms of the cortical swallowing network as well as peripheral neuromuscular involvement have been suggested to contribute to its multifactorial genesis. Diagnostic screening methods include PD-specific questionnaires and a modified water test. Fiber optic endoscopic evaluation of swallowing (FEES) and videofluoroscopic swallowing study (VFSS), which complement each other, are the gold standard for evaluation of PD-related dysphagia. For evaluation of esophageal dysphagia, the high-resolution manometry (HRM) may be a helpful tool. In addition to dysphagia-specific treatment by speech and language therapists (SLTs), optimized dopaminergic medication is a meaningful therapeutic option. A promising novel method is intensive training of expiratory muscle strength (EMST). Deep brain stimulation does not seem to have a clinically relevant effect on swallowing function in PD. © Georg Thieme Verlag KG Stuttgart · New York.

  4. Computerized tomography of chest in emphysema and interstitial diseases diagnosis

    International Nuclear Information System (INIS)

    Souto Bayarri, M.; Malagari, K.; Ibarburen, C.; Arenas, G.; Correa Pombo, J.; Garcia Tahoces, P.; Tucker, D.; Barnes, G.T.; Luna, R.; Zerhouni, E.A.; Fraser, R.G.; Vidal Carrerira, J.J.

    1994-01-01

    To study the effect of increasing the spatial resolution on thin section (1.5 mm) computed tomography (CT) of the chest, we compared images reconstructed with the standard algorithm (SA) to three other images obtained with 1) a high spatial frequency algorithm, 2) retrospective targeting to a small field of view (FOV) reconstructed with the high spatial frequency algorithm, and 3) the same high spatial frequency algorithm with images acquired with the small (0.6 mm) rather the large (0.9 mm) focal spot. Examinations were performed on a phantom, on normal subjects, and on patients with emphysema and other diffuse lung diseases. Modulation transfer function (MTF) calculations revealed that higher resolution was achieved on the small focal spot and high spatial frequency algorithm than on the standard algorithm. Evaluation of the four images from 25 normal subjects, 16 patients with emphysema and 9 with interstitial disease was performed by means of an ROC study. Results from the areas under the ROC curves, sensitivity and specificity have shown that images reconstructed with the high spatial frequency algorithm were preferred. We conclude that the use of a high spatial frequency algorithm increases spatial resolution and improves visibility of lung parenchyma. Although more evaluation is needed, the potential of increasing spatial resolution further by using a smaller focal spot is currently limited by the mas Available per slice and the associated increased level of quantum noise. (Author)

  5. Nanotechnology in diagnosis and treatment of coronary artery disease.

    Science.gov (United States)

    Karimi, Mahdi; Zare, Hossein; Bakhshian Nik, Amirala; Yazdani, Narges; Hamrang, Mohammad; Mohamed, Elmira; Sahandi Zangabad, Parham; Moosavi Basri, Seyed Masoud; Bakhtiari, Leila; Hamblin, Michael R

    2016-01-01

    Nanotechnology could provide a new complementary approach to treat coronary artery disease (CAD) which is now one of the biggest killers in the Western world. The course of events, which leads to atherosclerosis and CAD, involves many biological factors and cellular disease processes which may be mitigated by therapeutic methods enhanced by nanotechnology. Nanoparticles can provide a variety of delivery systems for cargoes such as drugs and genes that can address many problems within the arteries. In order to improve the performance of current stents, nanotechnology provides different nanomaterial coatings, in addition to controlled-release nanocarriers, to prevent in-stent restenosis. Nanotechnology can increase the efficiency of drugs, improve local and systematic delivery to atherosclerotic plaques and reduce the inflammatory or angiogenic response after intravascular intervention. Nanocarriers have potential for delivery of imaging and diagnostic agents to precisely targeted destinations. This review paper will cover the current applications and future outlook of nanotechnology, as well as the main diagnostic methods, in the treatment of CAD.

  6. Nuclear medicine for diagnosis in benign diseases of the skeleton

    International Nuclear Information System (INIS)

    Feine, U.

    1992-01-01

    In summary, the lecture presents today's state of nuclear medical diganostics in benign bone disease, the radiopharmaceuticals, and the methods used. Besides the 99 m-Tc-labeled diphosphonates a couple of additional radioactive labeled substances play an important part in bone scintigraphic imaging especially in scanning inflammatory bone disease and the bone marrow. There are several substances available to label leucocytes and human immunoglobulins. Concerning the methods the performance of the 3-phase bone scanning and the application of SPECT becomes increasingly important. In detail discussed are among other methods the inflammation-scanning in osteomyelitis, the scintigraphic imaging in benign bone tumors and tumor like lesions, in circulation disorders of the bone with necroses and hyperperfusion (reflex sympathetic dystrophy, transient hip osteoporosis), and in bone lesions following trauma or stress, for example also in battered child syndrome. The indication to the different imaging procedures as X-ray, computed tomography, nuclear magnetic resonance, and scintigraphic imaging are discussed, whereby the scintiscanning urges its place, mainly due to good specifity, in documenting the different functional states of the bone such as inflammation, perfusion, necrosis, tumor and/or bone marrow infiltration. (orig.) [de

  7. Multimodal structural MRI in the diagnosis of motor neuron diseases.

    Science.gov (United States)

    Ferraro, Pilar M; Agosta, Federica; Riva, Nilo; Copetti, Massimiliano; Spinelli, Edoardo Gioele; Falzone, Yuri; Sorarù, Gianni; Comi, Giancarlo; Chiò, Adriano; Filippi, Massimo

    2017-01-01

    This prospective study developed an MRI-based method for identification of individual motor neuron disease (MND) patients and test its accuracy at the individual patient level in an independent sample compared with mimic disorders. 123 patients with amyotrophic lateral sclerosis (ALS), 44 patients with predominantly upper motor neuron disease (PUMN), 20 patients with ALS-mimic disorders, and 78 healthy controls were studied. The diagnostic accuracy of precentral cortical thickness and diffusion tensor (DT) MRI metrics of corticospinal and motor callosal tracts were assessed in a training cohort and externally proved in a validation cohort using a random forest analysis. In the training set, precentral cortical thickness showed 0.86 and 0.89 accuracy in differentiating ALS and PUMN patients from controls, while DT MRI distinguished the two groups from controls with 0.78 and 0.92 accuracy. In ALS vs controls, the combination of cortical thickness and DT MRI metrics (combined model) improved the classification pattern (0.91 accuracy). In the validation cohort, the best accuracy was reached by DT MRI (0.87 and 0.95 accuracy in ALS and PUMN vs mimic disorders). The combined model distinguished ALS and PUMN patients from mimic syndromes with 0.87 and 0.94 accuracy. A multimodal MRI approach that incorporates motor cortical and white matter alterations yields statistically significant improvement in accuracy over using each modality separately in the individual MND patient classification. DT MRI represents the most powerful tool to distinguish MND from mimic disorders.

  8. Hyperthyroidism in Graves disease. Current trends in management and diagnosis

    International Nuclear Information System (INIS)

    Haibach, H.

    1976-01-01

    The radioimmunoassay for T 3 is now widely available and is a useful diagnostic tool for hyperthyroidism, especially in T 3 -thyrotoxicosis. It is an essential tool in the management of hyperthyroidism that persists after treatment with normal T 4 serum levels or, in euthyroid cases, with low T 4 serum levels. In these conditions, it reflects the metabolic state more accurately than serum levels of T 4 . A promising new test is the response of radioimmunoassayable TSH to protirelin relin (TRH) administration. An absent response indicates pituitary suppression and thyroid autonomy as seen in frank hyperthyroidism or euthyroid Graves disease, treated or untreated. It is safer and quicker than the conventional T 3 suppression test of thyroid radioactive iodine uptake and may replace it at least partly in the future. The recently recognized sharp decline in the remission rate of patients subjected to thyroid drug therapy in the last decade has made this treatment much less efficacious. By necessity, it will probably lead to greater reliance on treatment with radioactive iodine in the majority of the patients with the hyperthyroidism of Graves disease

  9. Endothelial Progenitor Cells for Diagnosis and Prognosis in Cardiovascular Disease

    Directory of Open Access Journals (Sweden)

    Caterina Oriana Aragona

    2016-01-01

    Full Text Available Objective. To identify, evaluate, and synthesize evidence on the predictive power of circulating endothelial progenitor cells (EPCs in cardiovascular disease, through a systematic review of quantitative studies. Data Sources. MEDLINE was searched using keywords related to “endothelial progenitor cells” and “endothelium” and, for the different categories, respectively, “smoking”; “blood pressure”; “diabetes mellitus” or “insulin resistance”; “dyslipidemia”; “aging” or “elderly”; “angina pectoris” or “myocardial infarction”; “stroke” or “cerebrovascular disease”; “homocysteine”; “C-reactive protein”; “vitamin D”. Study Selection. Database hits were evaluated against explicit inclusion criteria. From 927 database hits, 43 quantitative studies were included. Data Syntheses. EPC count has been suggested for cardiovascular risk estimation in the clinical practice, since it is currently accepted that EPCs can work as proangiogenic support cells, maintaining their importance as regenerative/reparative potential, and also as prognostic markers. Conclusions. EPCs showed an important role in identifying cardiovascular risk conditions, and to suggest their evaluation as predictor of outcomes appears to be reasonable in different defined clinical settings. Due to their capability of proliferation, circulation, and the development of functional progeny, great interest has been directed to therapeutic use of progenitor cells in atherosclerotic diseases. This trial is registered with registration number: Prospero CRD42015023717.

  10. [Diagnosis and therapy of anemia in chronic diseases].

    Science.gov (United States)

    Scudla, V; Adam, Z; Scudlová, M

    2001-06-01

    The article deals with contemporary views on anaemia associated with chronic diseases. The authors present the definition of this nosological unit, draw attention to its high incidence in clinical practice and fact that it is frequently mistaken for iron deficiency anaemia. The authors submit a review of the most frequent diseases which cause the development of this type of anaemia and analyze the role of activation of the system of cellular immunity, the monocyte-macrophage system, agents of the cytokine network in inhibition of proliferation and differentiation of erythroid precursors, reduced production of endogenous erythropoietin with a reduced sensitivity of erythroid progenitor cells to its action and impaired iron homeostasis and inhibition of its reutilization. Special attention is devoted to diagnostic and differential diagnostic criteria in relation to other types of anaemia caused by impaired haeme synthesis and some secondary multifactorially conditioned types of anaemia. More detailed attention is paid to the diagnostic value of evaluating serum levels of soluble transferrin receptors and explanation of the asset of calculation of the transferrin receptor/ferririn index as a sensitive indicator of latent sideropenia as well as the Fe-absorption test using low oral iron doses. Part of the paper is also an account of contemporary possibilities of treatment including the use of the recombinant form of human erythropoietin, and attention is drawn to the unsuitability and pitfalls of iron therapy in this type of anaemia.

  11. Improved apparatus for predictive diagnosis of rotator cuff disease

    Science.gov (United States)

    Pillai, Anup; Hall, Brittany N.; Thigpen, Charles A.; Kwartowitz, David M.

    2014-03-01

    Rotator cuff disease impacts over 50% of the population over 60, with reports of incidence being as high as 90% within this population, causing pain and possible loss of function. The rotator cuff is composed of muscles and tendons that work in tandem to support the shoulder. Heavy use of these muscles can lead to rotator cuff tear, with the most common causes is age-related degeneration or sport injuries, both being a function of overuse. Tears ranges in severity from partial thickness tear to total rupture. Diagnostic techniques are based on physical assessment, detailed patient history, and medical imaging; primarily X-ray, MRI and ultrasonography are the chosen modalities for assessment. The final treatment technique and imaging modality; however, is chosen by the clinician is at their discretion. Ultrasound has been shown to have good accuracy for identification and measurement of full-thickness and partial-thickness rotator cuff tears. In this study, we report on the progress and improvement of our method of transduction and analysis of in situ measurement of rotator cuff biomechanics. We have improved the ability of the clinician to apply a uniform force to the underlying musculotendentious tissues while simultaneously obtaining the ultrasound image. This measurement protocol combined with region of interest (ROI) based image processing will help in developing a predictive diagnostic model for treatment of rotator cuff disease and help the clinicians choose the best treatment technique.

  12. Gastroesophageal reflux disease - unit description, diagnosis and treatment

    Directory of Open Access Journals (Sweden)

    Michał Raban

    2017-07-01

    Full Text Available Many GPs are increasingly dealing with patients complaining of ailments likely to suggest gastro-esophageal reflux disease (GERD. These symptoms include heartburn, abdominal pain, and a feeling of esophageal reflux (regurgitation. GERD is one of the most common gastrointestinal diseases that gastroenterologists meet in their practice (1, 2. In North America the problem is affected from 18.1% to even 27.8% of the population. The situation is similar in Europe, where the proportion of people with reflux symptoms is in the range of 8.8% - 25.9%. Among European countries, the prevalence of GERD symptoms is higher in the north of the continent than in the south. The growing problem of overweight and obesity that makes GERD more and more recognized in the population of children and adolescents (3 is a worrying fact. Interestingly, reflux-related complaints are much less frequent in eastern Asia, affecting only 2.5% -7.8% of the population (4.

  13. Whole-Genome Sequences of Two Borrelia afzelii and Two Borrelia garinii Lyme Disease Agent Isolates

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-12-01

    Human Lyme disease is commonly caused by several species of spirochetes in the Borrelia genus. In Eurasia these species are largely Borrelia afzelii, B. garinii, B. burgdorferi, and B. bavariensis sp. nov. Whole-genome sequencing is an excellent tool for investigating and understanding the influence of bacterial diversity on the pathogenesis and etiology of Lyme disease. We report here the whole-genome sequences of four isolates from two of the Borrelia species that cause human Lyme disease, B. afzelii isolates ACA-1 and PKo and B. garinii isolates PBr and Far04.

  14. The value of the abnormalities of bronchovascular bundles in the diagnosis of diffused lung diseases

    International Nuclear Information System (INIS)

    Li Tieyi; Ji Jingling

    1997-01-01

    To evaluate the abnormalities of bronchovascular bundles in the differential diagnosis of the diffuse lung disease, seventy-two patients with diffuse lung diseases were evaluated, 15 of 72 patients were pathologically proven and the others clinically proven. Of these 72 patients, there were 33 patients with diffuse pulmonary interstitial disease, 5 patients with pulmonary parenchymal disease, 14 patients with bronchial disease, and 20 patients with disseminated disease. All patients had conventional CT scan of the chest, some also had HRCT scan. All CT images were jointly reviewed by two radiologists. The features of the abnormalities of bronchovascular bundles included: (1) Thinning of bronchovascular bundles, predominantly seen in diffuse interstitial disease of lung and chronic bronchitis; (2) thickening of bronchovascular bundles, predominantly seen in interstitial diseases and disseminated lung diseases such as sarcoidosis and lymphangitis carcinomatosis with beaded appearance of bronchovascular bundles; (3) Increased visibility of bronchovascular bundles, predominantly seen in bronchiolitis and disseminated lung diseases. CT features of the abnormalities of bronchovascular bundles are present in 80% of diffuse lung diseases. The features are not specific, but the beaded bronchovascular bundles are always seen in sarcoidosis and lymphangitis carcinomatosis. In making a distinction between idiopathic pulmonary fibrosis and chronic bronchitis complicated with interstitial fibrosis, the position of diaphragm is of value in differential diagnosis, normal or elevated diaphragm is usually seen in the former, while low and flattened diaphragm in the latter. Change of the appearance of bronchovascular bundles from normality to abnormality reflects the process of development of the lung disease

  15. 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.

  16. 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.

  17. 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

  18. Common crus aplasia: diagnosis by 3D volume rendering imaging using 3DFT-CISS sequence

    International Nuclear Information System (INIS)

    Kim, H.J.; Song, J.W.; Chon, K.-M.; Goh, E.-K.

    2004-01-01

    AIM: The purpose of this study was to evaluate the findings of three-dimensional (3D) volume rendering (VR) imaging in common crus aplasia (CCA) of the inner ear. MATERIALS AND METHODS: Using 3D VR imaging of temporal bone constructive interference in steady state (CISS) magnetic resonance (MR) images, we retrospectively reviewed seven inner ears of six children who were candidates for cochlear implants and who had been diagnosed with CCA. As controls, we used the same method to examine 402 inner ears of 201 patients who had no clinical symptoms or signs of sensorineural hearing loss. Temporal bone MR imaging (MRI) was performed with a 1.5 T MR machine using a CISS sequence, and VR of the inner ear was performed on a work station. Morphological image analysis was performed on rotation views of 3D VR images. RESULTS: In all seven cases, CCA was diagnosed by the absence of the common crus. The remaining superior semicircular canal (SCC) was normal in five and hypoplastic in two inner ears, while the posterior SCC was normal in all seven. One patient showed bilateral symmetrical CCA. Complicated combined anomalies were seen in the cochlea, vestibule and lateral SCC. CONCLUSION: 3D VR imaging findings with MR CISS sequence can directly diagnose CCA. This technique may be useful in delineating detailed anomalies of SCCs

  19. 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.

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

    Directory of Open Access Journals (Sweden)

    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