WorldWideScience

Sample records for clinical profile molecular

  1. New generation of breast cancer clinical trials implementing molecular profiling

    Institute of Scientific and Technical Information of China (English)

    Dimitrios Zardavas; Martine Piccart-Gebhart

    2016-01-01

    The implementation of molecular profiling technologies in oncology deepens our knowledge for the molecular landscapes of cancer diagnoses, identifying aberrations that could be linked with specific therapeutic vulnerabilities. In particular, there is an increasing list of molecularly targeted anticancer agents undergoing clinical development that aim to block specific molecular aberrations. This leads to a paradigm shift, with an increasing list of specific aberrations dictating the treatment of patients with cancer. This paradigm shift impacts the field of clinical trials, since the classical approach of having clinico-pathological disease characteristics dictating the patients' enrolment in oncology trials shifts towards the implementation of molecular profiling as pre-screening step. In order to facilitate the successful clinical development of these new anticancer drugs within specific molecular niches of cancer diagnoses, there have been developed new, innovative trial designs that could be classified as follows: i) longitudinal cohort studies that implement (or not) "nested" downstream trials, 2) studies that assess the clinical utility of molecular profiling, 3) "master" protocol trials, iv) "basket" trials, v) trials following an adaptive design. In the present article, we review these innovative study designs, providing representative examples from each category and we discuss the challenges that still need to be addressed in this era of new generation oncology trials implementing molecular profiling. Emphasis is put on the field of breast cancer clinical trials.

  2. Disease-specific target gene expression profiling of molecular imaging probes: database development and clinical validation.

    Science.gov (United States)

    Chan, Lawrence Wing-Chi; Ngo, Connie Hiu-Ching; Wang, Fengfeng; Zhao, Moss Y; Zhao, Mengying; Law, Helen Ka-Wai; Wong, Sze Chuen Cesar; Yung, Benjamin Yat-Ming

    2014-01-01

    Molecular imaging probes can target abnormal gene expression patterns in patients and allow early diagnosis of disease. For selecting a suitable imaging probe, the current Molecular Imaging and Contrast Agent Database (MICAD) provides descriptive and qualitative information on imaging probe characteristics and properties. However, MICAD does not support linkage with the expression profiles of target genes. The proposed Disease-specific Imaging Probe Profiling (DIPP) database quantitatively archives and presents the gene expression profiles of targets across different diseases, anatomic regions, and subcellular locations, providing an objective reference for selecting imaging probes. The DIPP database was validated with a clinical positron emission tomography (PET) study on lung cancer and an in vitro study on neuroendocrine cancer. The retrieved records show that choline kinase beta and glucose transporters were positively and significantly associated with lung cancer among the targets of 11C-choline and [18F]fluoro-2-deoxy-2-d-glucose (FDG), respectively. Their significant overexpressions corresponded to the findings that the uptake rate of FDG increased with tumor size but that of 11C-choline remained constant. Validated with the in vitro study, the expression profiles of disease-associated targets can indicate the eligibility of patients for clinical trials of the treatment probe. A Web search tool of the DIPP database is available at http://www.polyu.edu.hk/bmi/dipp/. PMID:25022454

  3. Molecular profiling of patients with colorectal cancer and matched targeted therapy in phase I clinical trials.

    Science.gov (United States)

    Dienstmann, Rodrigo; Serpico, Danila; Rodon, Jordi; Saura, Cristina; Macarulla, Teresa; Elez, Elena; Alsina, Maria; Capdevila, Jaume; Perez-Garcia, Jose; Sánchez-Ollé, Gessamí; Aura, Claudia; Prudkin, Ludmila; Landolfi, Stefania; Hernández-Losa, Javier; Vivancos, Ana; Tabernero, Josep

    2012-09-01

    Clinical experience increasingly suggests that molecular prescreening and biomarker enrichment strategies in phase I trials with targeted therapies will improve the outcomes of patients with cancer. In keeping with the exigencies of a personalized oncology program, tumors from patients with advanced chemorefractory colorectal cancer were analyzed for specific aberrations (KRAS/BRAF/PIK3CA mutations, PTEN and pMET expression). Patients were subsequently offered phase I trials with matched targeted agents (MTA) directed at the identified anomalies. During 2010 and 2011, tumor molecular analysis was conducted in 254 patients: KRAS mutations (80 of 254, 31.5%), BRAF mutations (24 of 196, 12.2%), PIK3CA mutations (15 of 114, 13.2%), KRAS and PIK3CA mutations (9 of 114, 7.9%), low PTEN expression (97 of 183, 53.0%), and high pMET expression (38 of 64, 59.4%). In total, 68 patients received 82 different MTAs: phosphoinositide 3-kinase (PI3K) pathway inhibitor (if PIK3CA mutation, n = 10; or low PTEN, n = 32), PI3K pathway inhibitor plus MEK inhibitor (if KRAS mutation, n = 10; or BRAF mutation, n = 1), second-generation anti-EGF receptor monoclonal antibodies (if wild-type KRAS, n = 11), anti-hepatocyte growth factor monoclonal antibody (if high pMET, n = 10), mTOR inhibitor plus anti-insulin-like growth factor-1 receptor monoclonal antibody (if low PTEN, n = 5), and BRAF inhibitor (if BRAF mutation, n = 3). Median time-to-treatment failure on MTA was 7.9 versus 16.3 weeks for their prior systemic antitumor therapy (P 16 weeks in 10 cases (12.2%). These results suggest that matching chemorefractory patients with colorectal cancer with targeted agents in phase I trials based on the current molecular profile does not confer a significant clinical benefit.

  4. Molecular profiling of liver tumors: classification and clinical translation for decision making.

    Science.gov (United States)

    Pinyol, Roser; Nault, Jean Charles; Quetglas, Iris M; Zucman-Rossi, Jessica; Llovet, Josep M

    2014-11-01

    Hepatocellular carcinoma (HCC) is a complex disease with a dismal prognosis. Consequently, a translational approach is required to personalized clinical decision making to improve survival of HCC patients. Molecular signatures from cirrhotic livers and single nucleotide polymorphism have been linked with HCC occurrence. Identification of high-risk populations will be useful to design chemopreventive trials. In addition, molecular signatures derived from tumor and nontumor samples are associated with early tumor recurrence due to metastasis and late tumor recurrence due to de novo carcinogenesis after curative treatment, respectively. Identification of patients with a high risk of relapse will guide adjuvant randomized trials. The genetic landscape drawn by next-generation sequencing has highlighted the genomic diversity of HCC. Genetic drivers recurrently mutated belong to different signaling pathways including telomere maintenance, cell-cycle regulators, chromatin remodeling, Wnt/b-catenin, RAS/RAF/MAPK kinase, and AKT/mTOR pathway. These cancer genes will be ideally targeted by biotherapies as a paradigm of stratified medicine adapted to tumor biology. PMID:25369299

  5. Epidemiology, clinical, immune, and molecular profiles of microsporidiosis and cryptosporidiosis among HIV/AIDS patients

    Directory of Open Access Journals (Sweden)

    Wumba R

    2012-07-01

    Full Text Available Roger Wumba,1 Benjamin Longo-Mbenza,2 Jean Menotti,3,4 Madone Mandina,5 Fabien Kintoki,5 Nani Hippolyte Situakibanza,1,5 Marie Kapepela Kakicha,6 Josue Zanga,1 Kennedy Mbanzulu-Makola,1 Tommy Nseka,1 Jean Pierre Mukendi,1 Eric Kendjo,7 Jean Sala,1 Marc Thellier7,81Department of Tropical Medicine, Infectious and Parasitic Diseases, Department of Parasitology, University Clinic of Kinshasa, Faculty of Medicine, University of Kinshasa, Kinshasa, Congo; 2Faculty of Health Sciences, Walter Sisulu University, Eastern Cape, South Africa; 3Laboratory of Parasitology and Mycology, Saint-Louis Hospital, Public Assistance-Hospitals of Paris, Paris, France; 4Faculty of Medicine, Lariboisière-Saint-Louis, University of Paris VII, Paris, France; 5Department of Internal Medicine, University Clinic of Kinshasa, Faculty of Medicine, University of Kinshasa, Kinshasa, Congo; 6Department of Pediatrics, University Clinic of Kinshasa, Faculty of Medicine, University of Kinshasa, Kinshasa, Congo; 7National Center for Malaria Research, AP-HP, CHU Pitie Salpêtrière, Paris, France; 8Laboratory of Parasitology and Mycology, Pitié Salpêtrière Hospital, Public Assistance-Hospitals of Paris, Pierre and Marie Curie University, Paris, FranceBackground: The objective of this study was to determine the prevalence of intestinal parasites, with special emphasis on microsporidia and Cryptosporidium, as well as their association with human immunodeficiency virus (HIV symptoms, risk factors, and other digestive parasites. We also wish to determine the molecular biology definitions of the species and genotypes of microsporidia and Cryptosporidium in HIV patients.Methods: In this cross-sectional study, carried out in Kinshasa, Democratic Republic of the Congo, stool samples were collected from 242 HIV patients (87 men and 155 women with referred symptoms and risk factors for opportunistic intestinal parasites. The analysis of feces specimen were performed using Ziehl

  6. Clinical profile and molecular characterization of Galactosemia in Brazil: identification of seven novel mutations

    OpenAIRE

    Garcia, Daniel F.; Camelo, José S.; Molfetta, Greice A.; Turcato, Marlene; Souza, Carolina F. M.; Porta, Gilda; Steiner, Carlos E.; Silva, Wilson A

    2016-01-01

    Background Classical Galactosemia (CG) is an inborn error of galactose metabolism caused by the deficiency of the galactose-1-phosphate uridyltransferase enzyme. It is transmitted as an autosomal recessive disease and is typically characterized by neonatal galactose intolerance, with complications ranging from neonatal jaundice and liver failure to late complications, such as motor and reproductive dysfunctions. Galactosemia is also heterogeneous from a molecular standpoint, with hundreds of ...

  7. Clinical Outcomes of Patients with Rare and Heavily Pretreated Solid Tumors Treated according to the Results of Tumor Molecular Profiling

    Science.gov (United States)

    Hayden, Ingrid

    2016-01-01

    Patients with heavily pretreated advanced cancer or with rare tumors are difficult to treat. Molecular profiling (MP) of tumors to identify biomarkers that predict potential outcomes with individual therapies is an emerging strategy to guide treatment decisions. Patients with rare tumors for which standard-of-care therapy was unavailable or more common tumors for which standard-of-care options had been exhausted underwent MP at a single Australian center. Data regarding treating physicians' choice of therapy, MP results and recommendations, and patient outcomes were collected. Seven patients had received prior standard first-line therapy (PST), 16 had rare tumors, and 31 had been heavily pretreated (HPT; ≥2 prior lines). Most treatments suggested by MP (541/594; 91.1%) were common chemotherapy drugs available in generic formulations. MP-guided therapy recommendations differed from physician's recommendations in 48 patients (88.9%). MP-guided therapy produced clinical benefit (improved QOL and/or performance status, symptoms, bodyweight, or RECIST) in 19/31 (61.3%), 11/16 (68.8%), and 3/7 (42.9%) patients with HPTs, rare tumors, and PSTs, respectively, and had a PFS ratio ≥1.3 in 22/37 evaluable patients (59.5%; 95% confidence interval 44–76%). The null hypothesis that ≤15% of these patients would have a PFS ratio ≥1.3 was rejected (one-sided p selection is feasible in clinical practice and may improve patient outcomes. PMID:27525268

  8. Genomic profiling of lung adenocarcinoma patients reveals therapeutic targets and confers clinical benefit when standard molecular testing is negative

    Science.gov (United States)

    Lim, Sun Min; Kim, Eun Young; Kim, Hye Ryun; Ali, Siraj M.; Greenbowe, Joel R.; Shim, Hyo Sup; Chang, Hyun; Lim, Seungtaek; Paik, Soonmyung; Cho, Byoung Chul

    2016-01-01

    Background: Identification of clinically relevant oncogenic drivers in advanced cancer is critical in selecting appropriate targeted therapy. Using next-generation sequencing (NGS)-based clinical cancer gene assay, we performed comprehensive genomic profiling (CGP) of advanced cases of lung adenocarcinoma. Methods: Formalin-fixed paraffin-embedded tumors from 51 lung adenocarcinoma patients whose tumors previously tested negative for EGFR/KRAS/ALK by conventional methods were collected, and CGP was performed via hybridization capture of 4,557 exons from 287 cancer-related genes and 47 introns from 19 genes frequently rearranged in cancer. Results: Genomic profiles of all 51 cases were obtained, with a median coverage of 564x and a total of 190 individual genomic alterations (GAs). GAs per specimen was a mean of 3.7 (range 0-10).Cancer genomes are characterized by 50% (80/190) non-synonymous base substitutions, 15% (29/190) insertions or deletion, and 3% (5/190) splice site mutation. TP53 mutation was the most common GAs (15%, n=29/190), followed by CDKN2A homozygous loss (5%, n=10/190), KRAS mutation (4%, n=8/190), EGFR mutation (4%, n=8/190) and MDM2 amplification (2%, n=5/190). As per NCCN guidelines, targetable GAs were identified in 16 patients (31%) (BRAF mutation [n=1], EGFR mutation [n=8], ERBB2 mutation [n=4], MET amplification [n=1], KIF5B-RET rearrangement [n=2], CCDC6-RET rearrangement [n=1], CD74-ROS1 rearrangement [n=1], EZR-ROS1 rearrangement [n=5], and SLC34A2-ROS1 rearrangement [n=1]). Conclusion: Fifty eight percent of patients wild type by standard testing for EGFR/KRAS/ALK have GAs identifiable by CGP that suggest benefit from target therapy. CGP used when standard molecular testing for NSCLC is negative can reveal additional avenues of benefit from targeted therapy. PMID:26992220

  9. Clinical profile and molecular diagnosis in patients of facioscapulohumeral dystrophy from Indian subcontinent

    Directory of Open Access Journals (Sweden)

    Tamhankar Parag

    2010-01-01

    Full Text Available Facioscapulohumeral dystrophy (FSHD is an autosomal dominant muscular dystrophy. We retrospectively studied three families (two Indian, one Nepalese with 12 affected members (male:female-7:5. Mean age at onset of weakness was 17.63 + 5.48 years. Patients were classified according to muscle groups affected (F-face, S-scapula, H-humeral, PG-pelvic girdle, P-peroneal, A-loss of independent ambulation: FSH-A (2, four FSH (4, SH (3, FSH-PG (2 and one: F (1. Progression of weakness was classified as F>S>P>PG in eight cases, S> F>P in one, static in three. Eleven patients had electromyographic findings suggestive of myopathy and one had features of neurogenic involvement. Molecular diagnosis was done by southern blotting using probe p13E-11 after digestion of genomic DNA with EcoRI and/or EcoRI/BlnI for twelve patients and three unaffected relatives. No EcoRI fragment smaller than 35 Kb was seen in unaffected subjects. Size of EcoRI fragment varied between 17 kb to 27 kb in affected subjects and was constant for affected members of the same family. Molecular diagnosis by southern blotting has helped to provide genetic counseling for the families.

  10. Clinical Outcomes of Patients with Rare and Heavily Pretreated Solid Tumors Treated according to the Results of Tumor Molecular Profiling.

    Science.gov (United States)

    Dean, Andrew; Byrne, Aisling; Marinova, Mira; Hayden, Ingrid

    2016-01-01

    Patients with heavily pretreated advanced cancer or with rare tumors are difficult to treat. Molecular profiling (MP) of tumors to identify biomarkers that predict potential outcomes with individual therapies is an emerging strategy to guide treatment decisions. Patients with rare tumors for which standard-of-care therapy was unavailable or more common tumors for which standard-of-care options had been exhausted underwent MP at a single Australian center. Data regarding treating physicians' choice of therapy, MP results and recommendations, and patient outcomes were collected. Seven patients had received prior standard first-line therapy (PST), 16 had rare tumors, and 31 had been heavily pretreated (HPT; ≥2 prior lines). Most treatments suggested by MP (541/594; 91.1%) were common chemotherapy drugs available in generic formulations. MP-guided therapy recommendations differed from physician's recommendations in 48 patients (88.9%). MP-guided therapy produced clinical benefit (improved QOL and/or performance status, symptoms, bodyweight, or RECIST) in 19/31 (61.3%), 11/16 (68.8%), and 3/7 (42.9%) patients with HPTs, rare tumors, and PSTs, respectively, and had a PFS ratio ≥1.3 in 22/37 evaluable patients (59.5%; 95% confidence interval 44-76%). The null hypothesis that ≤15% of these patients would have a PFS ratio ≥1.3 was rejected (one-sided p < 0.0001). In conclusion, using MP to guide therapy selection is feasible in clinical practice and may improve patient outcomes. PMID:27525268

  11. Molecular profiling of chordoma

    Science.gov (United States)

    SCHEIL-BERTRAM, STEFANIE; KAPPLER, ROLAND; VON BAER, ALEXANDRA; HARTWIG, ERICH; SARKAR, MICHAEL; SERRA, MASSIMO; BRÜDERLEIN, SILKE; WESTHOFF, BETTINA; MELZNER, INGO; BASSALY, BIRGIT; HERMS, JOCHEN; HUGO, HEINZ-HERMANN; SCHULTE, MICHAEL; MÖLLER, PETER

    2014-01-01

    The molecular basis of chordoma is still poorly understood, particularly with respect to differentially expressed genes involved in the primary origin of chordoma. In this study, therefore, we compared the transcriptional expression profile of one sacral chordoma recurrence, two chordoma cell lines (U-CH1 and U-CH2) and one chondrosarcoma cell line (U-CS2) with vertebral disc using a high-density oligonucleotide array. The expression of 65 genes whose mRNA levels differed significantly (p<0.001; ≥6-fold change) between chordoma and control (vertebral disc) was identified. Genes with increased expression in chordoma compared to control and chondrosarcoma were most frequently located on chromosomes 2 (11%), 5 (8%), 1 and 7 (each 6%), whereas interphase cytogenetics of 33 chordomas demonstrated gains of chromosomal material most prevalent on 7q (42%), 12q (21%), 17q (21%), 20q (27%) and 22q (21%). The microarray data were confirmed for selected genes by quantitative polymerase chain reaction analysis. As in other studies, we showed the expression of brachyury. We demonstrate the expression of new potential candidates for chordoma tumorigenesis, such as CD24, ECRG4, RARRES2, IGFBP2, RAP1, HAI2, RAB38, osteopontin, GalNAc-T3, VAMP8 and others. Thus, we identified and validated a set of interesting candidate genes whose differential expression likely plays a role in chordoma. PMID:24452533

  12. Review of the molecular profile and modern prognostic markers for gastric lymphoma: how do they affect clinical practice?

    Science.gov (United States)

    Alevizos, Leonidas; Gomatos, Ilias P; Smparounis, Spyridon; Konstadoulakis, Manousos M; Zografos, Georgios

    2012-04-01

    Primary gastric lymphoma is a rare cancer of the stomach with an indeterminate prognosis. Recently, a series of molecular prognostic markers has been introduced to better describe this clinical entity. This review describes the clinical importance of several oncogenes, apoptotic genes and chromosomal mutations in the initiation and progress of primary non-Hodgkin gastric lymphoma and their effect on patient survival. We also outline the prognostic clinical importance of certain cellular adhesion molecules, such as ICAM and PECAM-1, in patients with gastric lymphoma, and we analyze the correlation of these molecules with apoptosis, angiogenesis, tumour growth and metastatic potential. We also focus on the host-immune response and the impact of Helicobacter pylori infection on gastric lymphoma development and progression. Finally, we explore the therapeutic methods currently available for gastric lymphoma, comparing the traditional invasive approach with more recent conservative options, and we stress the importance of the application of novel molecular markers in clinical practice.

  13. Breast Molecular Profiling and Radiotherapy Considerations.

    Science.gov (United States)

    Mahmoud, Omar; Haffty, Bruce G

    2016-01-01

    The last decade has seen major changes in the management of breast cancer. Heterogeneity regarding histology, therapeutic response, dissemination patterns, and patient outcome is evident. Molecular profiling provides an accurate tool to predict treatment outcome compared with classical clinicopathologic features. The genomic profiling unveiled the heterogeneity of breast cancer and identified distinct biologic subtypes. These advanced techniques were integrated into the clinical management; predicting systemic therapy benefit and overall survival. Utilizing genotyping to guide locoregional management decisions needs further characterization. In this chapter we will review available data on molecular classification of breast cancer, their association with locoregional outcome, their radiobiological properties and radiotherapy considerations. PMID:26987532

  14. Colon cancer molecular subtypes identified by expression profiling and associated to stroma, mucinous type and different clinical behavior

    International Nuclear Information System (INIS)

    Colon cancer patients with the same stage show diverse clinical behavior due to tumor heterogeneity. We aimed to discover distinct classes of tumors based on microarray expression patterns, to analyze whether the molecular classification correlated with the histopathological stages or other clinical parameters and to study differences in the survival. Hierarchical clustering was performed for class discovery in 88 colon tumors (stages I to IV). Pathways analysis and correlations between clinical parameters and our classification were analyzed. Tumor subtypes were validated using an external set of 78 patients. A 167 gene signature associated to the main subtype was generated using the 3-Nearest-Neighbor method. Coincidences with other prognostic predictors were assesed. Hierarchical clustering identified four robust tumor subtypes with biologically and clinically distinct behavior. Stromal components (p < 0.001), nuclear β-catenin (p = 0.021), mucinous histology (p = 0.001), microsatellite-instability (p = 0.039) and BRAF mutations (p < 0.001) were associated to this classification but it was independent of Dukes stages (p = 0.646). Molecular subtypes were established from stage I. High-stroma-subtype showed increased levels of genes and altered pathways distinctive of tumour-associated-stroma and components of the extracellular matrix in contrast to Low-stroma-subtype. Mucinous-subtype was reflected by the increased expression of trefoil factors and mucins as well as by a higher proportion of MSI and BRAF mutations. Tumor subtypes were validated using an external set of 78 patients. A 167 gene signature associated to the Low-stroma-subtype distinguished low risk patients from high risk patients in the external cohort (Dukes B and C:HR = 8.56(2.53-29.01); Dukes B,C and D:HR = 1.87(1.07-3.25)). Eight different reported survival gene signatures segregated our tumors into two groups the Low-stroma-subtype and the other tumor subtypes. We have identified novel

  15. Molecular identification and antifungal susceptibility profiles of Candida parapsilosis complex species isolated from culture collection of clinical samples

    Directory of Open Access Journals (Sweden)

    Fábio Silvestre Ataides

    2015-08-01

    Full Text Available AbstractINTRODUCTION:Candida parapsilosis is a common yeast species found in cases of onychomycosis and candidemia associated with infected intravascular devices. In this study, we differentiated Candida parapsilosis sensu stricto, Candida orthopsilosis , and Candida metapsilosis from a culture collection containing blood and subungual scraping samples. Furthermore, we assessed the in vitro antifungal susceptibility of these species to fluconazole, itraconazole, voriconazole, posaconazole, amphotericin B, and caspofungin.METHODS:Differentiation of C. parapsilosis complex species was performed by amplification of the secondary alcohol dehydrogenase (SADH gene and digestion by the restriction enzyme Ban I. All isolates were evaluated for the determination of minimal inhibitory concentrations using Etest, a method for antifungal susceptibility testing.RESULTS:Among the 87 isolates, 78 (89.7% were identified as C. parapsilosis sensu stricto , five (5.7% were identified as C. orthopsilosis , and four (4.6% were identified as C. metapsilosis . Analysis of antifungal susceptibility showed that C. parapsilosis sensu strictoisolates were less susceptible to amphotericin B and itraconazole. One C. parapsilosis sensu stricto isolate was resistant to amphotericin B and itraconazole. Moreover, 10.2% of C. parapsilosis sensu stricto isolates were resistant to caspofungin. Two C. parapsilosis sensu strictoisolates and one C. metapsilosis isolate were susceptible to fluconazole in a dose-dependent manner.CONCLUSIONS:We reported the first molecular identification of C. parapsilosiscomplex species in State of Goiás, Brazil. Additionally, we showed that although the three species exhibited differences in antifungal susceptibility profiles, the primary susceptibility of this species was to caspofungin.

  16. Ultrasound molecular imaging: Moving toward clinical translation

    Energy Technology Data Exchange (ETDEWEB)

    Abou-Elkacem, Lotfi; Bachawal, Sunitha V.; Willmann, Jürgen K., E-mail: willmann@stanford.edu

    2015-09-15

    Highlights: • Ultrasound molecular imaging is a highly sensitive modality. • A clinical grade ultrasound contrast agent has entered first in human clinical trials. • Several new potential future clinical applications of ultrasound molecular imaging are being explored. - Abstract: Ultrasound is a widely available, cost-effective, real-time, non-invasive and safe imaging modality widely used in the clinic for anatomical and functional imaging. With the introduction of novel molecularly-targeted ultrasound contrast agents, another dimension of ultrasound has become a reality: diagnosing and monitoring pathological processes at the molecular level. Most commonly used ultrasound molecular imaging contrast agents are micron sized, gas-containing microbubbles functionalized to recognize and attach to molecules expressed on inflamed or angiogenic vascular endothelial cells. There are several potential clinical applications currently being explored including earlier detection, molecular profiling, and monitoring of cancer, as well as visualization of ischemic memory in transient myocardial ischemia, monitoring of disease activity in inflammatory bowel disease, and assessment of arteriosclerosis. Recently, a first clinical grade ultrasound contrast agent (BR55), targeted at a molecule expressed in neoangiogenesis (vascular endothelial growth factor receptor type 2; VEGFR2) has been introduced and safety and feasibility of VEGFR2-targeted ultrasound imaging is being explored in first inhuman clinical trials in various cancer types. This review describes the design of ultrasound molecular imaging contrast agents, imaging techniques, and potential future clinical applications of ultrasound molecular imaging.

  17. Molecular profiling in glioblastoma: prelude to personalized treatment.

    Science.gov (United States)

    Mladkova, Nikol; Chakravarti, Arnab

    2009-01-01

    The purpose of this review is to provide an up-to-date summary of the current knowledge and understanding of the molecular alterations and pathways relevant to the clinical outcome of glioblastoma patients and their potential use in designing personalized treatment for these patients. This article also discusses the potential of molecular profiling as a diagnostic modality, possible therapeutic implications of MGMT promoter methylation, the targeted inhibition of angiogenesis, and assessment of the tumor's molecular background with respect to PI3K/AKT pathway activation and associated molecules (EGFR, EGFRvIII, PTEN). PMID:19080742

  18. The importance of molecular profiling in predicting response to epidermal growth factor receptor family inhibitors in non-small-cell lung cancer: focus on clinical trial results.

    Science.gov (United States)

    Tsao, Anne S; Papadimitrakopoulou, Vassiliki

    2013-07-01

    In recent years, the epidermal growth factor receptor (EGFR) family has become a key focus of non-small-cell lung cancer biology and targeted therapies, such as the reversible EGFR tyrosine kinase inhibitors erlotinib and gefitinib. Initially, response to these agents was associated with certain demographic and clinical characteristics; subsequently, it was discovered that these subgroups were more likely to harbor specific mutations in the EGFR gene that enhanced tumor response. However, the presence of these mutations does not equate to therapeutic success. Other aspects of EGFR family signaling, including other types of EGFR mutations, EGFR protein expression, EGFR gene amplification, mediators of downstream signaling, and other receptors with similar downstream pathways may all play a role in response or resistance to treatment. The identification of these and other molecular determinants is driving the development of novel therapies designed to achieve improved clinical outcomes in patients.

  19. Clinical profile of HIV infection

    Directory of Open Access Journals (Sweden)

    Khopkar Uday

    1992-01-01

    Full Text Available HIV seropositivity rate of 14 percent was observed amongst STD cases. Heterosexual contact with prostitutes was the main risk factor. Fever, anorexia, weight loss, lymphadenopathy and tuberculosis were useful clinical leads. Genital ulcers, especially chancroid, were common in seropositivies. Alopecia of unknown cause, atypical pyoderma, seborrhea, zoster, eruptive mollusca and sulfa-induced erythema multiforme were viewed with suspicion in high risk groups. Purpura fulminans, fulminant chancroid, vegetating pyoderma and angioedema with purpura were unique features noted in this study.

  20. Incorporate gene signature profiling into routine molecular testing

    Directory of Open Access Journals (Sweden)

    Neng Chen

    2013-12-01

    Full Text Available The success of gene and gene expression profiling, such as the Oncotype DX® test for breast cancer patients, demonstrates that as technology becomes more sophisticated molecular diagnostics will continue to play a more important role in disease management in the future. Such promises have been and continue to be enabled by advances in real-time PCR, microarray detection platforms and next generation sequencing technologies. Practical adoption of new technologies into routine clinical care, however, has not always been a smooth ride. Challenges lie on several fronts: establishment of clinical validity in large scale patient population, mechanisms of incorporating molecular tests into standard care, and keeping up with the pace of ever changing technologies in regulated clinical laboratories, just to name a few. This review's goals are to educate, to stimulate discussion and to provoke efforts to build consensus, share resources, and establish standards in order to realize the promises of genomic technologies for routine patient care.

  1. Molecular profiling reveals primary mesothelioma cell lines recapitulate human disease.

    Science.gov (United States)

    Chernova, T; Sun, X M; Powley, I R; Galavotti, S; Grosso, S; Murphy, F A; Miles, G J; Cresswell, L; Antonov, A V; Bennett, J; Nakas, A; Dinsdale, D; Cain, K; Bushell, M; Willis, A E; MacFarlane, M

    2016-07-01

    Malignant mesothelioma (MM) is an aggressive, fatal tumor strongly associated with asbestos exposure. There is an urgent need to improve MM patient outcomes and this requires functionally validated pre-clinical models. Mesothelioma-derived cell lines provide an essential and relatively robust tool and remain among the most widely used systems for candidate drug evaluation. Although a number of cell lines are commercially available, a detailed comparison of these commercial lines with freshly derived primary tumor cells to validate their suitability as pre-clinical models is lacking. To address this, patient-derived primary mesothelioma cell lines were established and characterized using complementary multidisciplinary approaches and bioinformatic analysis. Clinical markers of mesothelioma, transcriptional and metabolic profiles, as well as the status of p53 and the tumor suppressor genes CDKN2A and NF2, were examined in primary cell lines and in two widely used commercial lines. Expression of MM-associated markers, as well as the status of CDKN2A, NF2, the 'gatekeeper' in MM development, and their products demonstrated that primary cell lines are more representative of the tumor close to its native state and show a degree of molecular diversity, thus capturing the disease heterogeneity in a patient cohort. Molecular profiling revealed a significantly different transcriptome and marked metabolic shift towards a greater glycolytic phenotype in commercial compared with primary cell lines. Our results highlight that multiple, appropriately characterised, patient-derived tumor cell lines are required to enable concurrent evaluation of molecular profiles versus drug response. Furthermore, application of this approach to other difficult-to-treat tumors would generate improved cellular models for pre-clinical evaluation of novel targeted therapies. PMID:26891694

  2. Quantum Dot Platform for Single-Cell Molecular Profiling

    Science.gov (United States)

    Zrazhevskiy, Pavel S.

    preparation and specimen labeling, requiring no advanced technical skills and being directly applicable for a wide range of molecular profiling studies. Utilization of quantum dot platform for single-cell molecular profiling promises to greatly benefit both biomedical research and clinical diagnostics by providing a tool for addressing phenotypic heterogeneity within large cell populations, opening access to studying low-abundance events often masked or completely erased by batch processing, and elucidating biomarker signatures of diseases critical for accurate diagnostics and targeted therapy.

  3. Profiling critical cancer gene mutations in clinical tumor samples.

    Directory of Open Access Journals (Sweden)

    Laura E MacConaill

    Full Text Available BACKGROUND: Detection of critical cancer gene mutations in clinical tumor specimens may predict patient outcomes and inform treatment options; however, high-throughput mutation profiling remains underdeveloped as a diagnostic approach. We report the implementation of a genotyping and validation algorithm that enables robust tumor mutation profiling in the clinical setting. METHODOLOGY: We developed and implemented an optimized mutation profiling platform ("OncoMap" to interrogate approximately 400 mutations in 33 known oncogenes and tumor suppressors, many of which are known to predict response or resistance to targeted therapies. The performance of OncoMap was analyzed using DNA derived from both frozen and FFPE clinical material in a diverse set of cancer types. A subsequent in-depth analysis was conducted on histologically and clinically annotated pediatric gliomas. The sensitivity and specificity of OncoMap were 93.8% and 100% in fresh frozen tissue; and 89.3% and 99.4% in FFPE-derived DNA. We detected known mutations at the expected frequencies in common cancers, as well as novel mutations in adult and pediatric cancers that are likely to predict heightened response or resistance to existing or developmental cancer therapies. OncoMap profiles also support a new molecular stratification of pediatric low-grade gliomas based on BRAF mutations that may have immediate clinical impact. CONCLUSIONS: Our results demonstrate the clinical feasibility of high-throughput mutation profiling to query a large panel of "actionable" cancer gene mutations. In the future, this type of approach may be incorporated into both cancer epidemiologic studies and clinical decision making to specify the use of many targeted anticancer agents.

  4. Clinical emergencies: profile of hospital assistance

    Directory of Open Access Journals (Sweden)

    Monica Franco Coelho

    2013-05-01

    Full Text Available Changes in the morbidity and mortality profile from chronic non-communicable diseases affect the urgency/emergency care services. We aimed to characterize the profile of emergency clinical care, according to demographic and epidemiological variables and length of stay in a teaching hospital in the interior of São Paulo, 2007. This is a descriptive, exploratory and documentary research that used official data, analyzed by descriptive statistics, discussed based on the theoretical framework of reorganization of urgency and emergency clinical care. In this period there were 5,285 clinical assistances, most were male (54.1%, with elementary education (73.9%, aged from 18 to 59 years (62.8%. Diseases of the circulatory system were the most frequent and the average length of stay in the unit was less than 6 hours (39.8%. The characterization of clinical care in the urgency/emergency service enables the work organization in the study unit and in the hospital.

  5. Ex Vivo Drug Susceptibility Testing and Molecular Profiling of Clinical Plasmodium falciparum Isolates from Cambodia from 2008 to 2013 Suggest Emerging Piperaquine Resistance.

    Science.gov (United States)

    Chaorattanakawee, Suwanna; Saunders, David L; Sea, Darapiseth; Chanarat, Nitima; Yingyuen, Kritsanai; Sundrakes, Siratchana; Saingam, Piyaporn; Buathong, Nillawan; Sriwichai, Sabaithip; Chann, Soklyda; Se, Youry; Yom, You; Heng, Thay Kheng; Kong, Nareth; Kuntawunginn, Worachet; Tangthongchaiwiriya, Kuntida; Jacob, Christopher; Takala-Harrison, Shannon; Plowe, Christopher; Lin, Jessica T; Chuor, Char Meng; Prom, Satharath; Tyner, Stuart D; Gosi, Panita; Teja-Isavadharm, Paktiya; Lon, Chanthap; Lanteri, Charlotte A

    2015-08-01

    Cambodia's first-line artemisinin combination therapy, dihydroartemisinin-piperaquine (DHA-PPQ), is no longer sufficiently curative against multidrug-resistant Plasmodium falciparum malaria at some Thai-Cambodian border regions. We report recent (2008 to 2013) drug resistance trends in 753 isolates from northern, western, and southern Cambodia by surveying for ex vivo drug susceptibility and molecular drug resistance markers to guide the selection of an effective alternative to DHA-PPQ. Over the last 3 study years, PPQ susceptibility declined dramatically (geomean 50% inhibitory concentration [IC50] increased from 12.8 to 29.6 nM), while mefloquine (MQ) sensitivity doubled (67.1 to 26 nM) in northern Cambodia. These changes in drug susceptibility were significantly associated with a decreased prevalence of P. falciparum multidrug resistance 1 gene (Pfmdr1) multiple copy isolates and coincided with the timing of replacing artesunate-mefloquine (AS-MQ) with DHA-PPQ as the first-line therapy. Widespread chloroquine resistance was suggested by all isolates being of the P. falciparum chloroquine resistance transporter gene CVIET haplotype. Nearly all isolates collected from the most recent years had P. falciparum kelch13 mutations, indicative of artemisinin resistance. Ex vivo bioassay measurements of antimalarial activity in plasma indicated 20% of patients recently took antimalarials, and their plasma had activity (median of 49.8 nM DHA equivalents) suggestive of substantial in vivo drug pressure. Overall, our findings suggest DHA-PPQ failures are associated with emerging PPQ resistance in a background of artemisinin resistance. The observed connection between drug policy changes and significant reduction in PPQ susceptibility with mitigation of MQ resistance supports reintroduction of AS-MQ, in conjunction with monitoring of the P. falciparum mdr1 copy number, as a stop-gap measure in areas of DHA-PPQ failure.

  6. Molecular heterogeneity in glioblastoma: potential clinical implications

    Directory of Open Access Journals (Sweden)

    Nicole Renee Parker

    2015-03-01

    Full Text Available Glioblastomas, (grade 4 astrocytomas, are aggressive primary brain tumors characterized by histopathological heterogeneity. High resolution sequencing technologies have shown that these tumors also feature significant inter-tumoral molecular heterogeneity. Molecular subtyping of these tumors has revealed several predictive and prognostic biomarkers. However, intra-tumoral heterogeneity may undermine the use of single biopsy analysis for determining tumor genotype and has implications for potential targeted therapies. The clinical relevance and theories of tumoral molecular heterogeneity in glioblastoma are discussed.

  7. Papillomaviruses: Molecular and clinical aspects

    Energy Technology Data Exchange (ETDEWEB)

    Howley, P.M.; Broker, T.R.

    1985-01-01

    This book contains nine sections, each consisting of several papers. The section headings are : Papillomaviruses and Human Genital Tract Diseases;Papillomaviruses and Human Cutaneous Diseases, Papillomaviruses and Human Oral and Laryngeal Diseases;Therapeutic Approaches to Papillomavirus Infections;Animal Papillomaviruses;Molecular Biology;Transcription, Replication, and Genome Organization;Epithelial Cell Culture;Papillomavirus Transformation;and Viral Vectors.

  8. Clinical cytogenetics and molecular cytogenetics

    Institute of Scientific and Technical Information of China (English)

    LI Marilyn; PINKEL Daniel

    2006-01-01

    The short report will be focused on helping our students to understand commonly used conventional and cutting edge cytogenetic techniques and their clinical applications, the advances and drawbacks of each technique, and how to pick the right test(s) for a specific patient in order to achieve a proper diagnosis efficiently and economically.

  9. Identification of a myometrial molecular profile for dystocic labor.

    LENUS (Irish Health Repository)

    Brennan, Donal J

    2011-01-01

    The most common indication for cesarean section (CS) in nulliparous women is dystocia secondary to ineffective myometrial contractility. The aim of this study was to identify a molecular profile in myometrium associated with dystocic labor.

  10. Molecular Profiling of Prostate Cancer Patients

    OpenAIRE

    Nna, Emmanuel Okechukwu

    2009-01-01

    In the UK, more than 30 000 men are diagnosed annually with prostate cancer (PCa) and about 10 000 men die from it each year. Although several molecular markers have been associated with prostate cancer development and/ or progression, only few of them are used in diagnostic pathology. The current standard tests include serum PSA test, digital rectal examination and histology of prostate biopsy. Recently the PCA-3 molecular test was approved in the European Union, and it is now...

  11. Clinically profiling pediatric patients with dengue

    Directory of Open Access Journals (Sweden)

    Sriram Pothapregada

    2016-01-01

    Full Text Available Objective: To study the clinical profile and outcome of dengue fever in children at a tertiary care hospital in Puducherry. Materials and Methods: All children (0-12 years of age diagnosed and confirmed as dengue fever from August 2012 to January 2015 were reviewed retrospectively from hospital case records as per the revised World Health Organization guidelines for dengue fever. The diagnosis was confirmed by NS1 antigen-based ELISA test or dengue serology for IgM and IgG antibodies, and the data were analyzed using SPSS 16.0 statistical software. After collecting the data, all the variables were summarized by descriptive statistics. Results: Among the 261 confirmed cases of dengue fever non-severe and severe dengue infection was seen in 60.9% and 39.1%, respectively. The mean age (standard deviation of the presentation was 6.9 + 3.3 years and male: female ratio was 1.2:1. The most common clinical manifestations were fever (94.6%, conjunctival congestion (89.6%, myalgia (81.9%, coryza (79.7%, headache (75.1%, palmar erythema (62.8%, and retro-orbital pain (51.3%. The common early warning signs at the time of admission were persistent vomiting (75.1%, liver enlargement (59.8%, cold and clammy extremities (45.2%, pain abdomen (31.0%, hypotension (29.5%, restlessness (26.4%, giddiness (23.0%, bleeding (19.9%, and oliguria (18.4%. The common manifestation of severe dengue infection was shock (39.1%, bleeding (19.9%, and multi-organ dysfunction (2.3%. The most common complications were liver dysfunction, acute respiratory distress syndrome, encephalopathy, pleural effusion, ascites, myocarditis, myositis, acute kidney injury, and disseminated intravascular coagulopathy. Platelet count did not always correlate well with the severity of bleeding. There were six deaths (2.3% and out of them four presented with impaired consciousness (66.6%. The common causes for poor outcome were multiorgan failure, encephalopathy, and fluid refractory shock

  12. Treating Tumors by Molecular Profile, Not Type.

    Science.gov (United States)

    2016-07-01

    Preliminary findings from MyPathway, an ongoing phase II basket trial, indicate that matching molecular abnormalities of patients' tumors to relevant targeted therapies-albeit outside a given drug's FDA-approved indication-is both feasible and promising. Notably, patients with HER2-amplified colorectal, bladder, and biliary cancers responded well to the combination of trastuzumab and pertuzumab. PMID:27277257

  13. Glycogen storage disease type I: clinical and laboratory profile

    Directory of Open Access Journals (Sweden)

    Berenice L. Santos

    2014-12-01

    Full Text Available OBJECTIVES: To characterize the clinical, laboratory, and anthropometric profile of a sample of Brazilian patients with glycogen storage disease type I managed at an outpatient referral clinic for inborn errors of metabolism. METHODS: This was a cross-sectional outpatient study based on a convenience sampling strategy. Data on diagnosis, management, anthropometric parameters, and follow-up were assessed. RESULTS: Twenty-one patients were included (median age 10 years, range 1-25 years, all using uncooked cornstarch therapy. Median age at diagnosis was 7 months (range, 1-132 months, and 19 patients underwent liver biopsy for diagnostic confirmation. Overweight, short stature, hepatomegaly, and liver nodules were present in 16 of 21, four of 21, nine of 14, and three of 14 patients, respectively. A correlation was found between height-for-age and BMI-for-age Z-scores (r = 0.561; p = 0.008. CONCLUSIONS: Diagnosis of glycogen storage disease type I is delayed in Brazil. Most patients undergo liver biopsy for diagnostic confirmation, even though the combination of a characteristic clinical presentation and molecular methods can provide a definitive diagnosis in a less invasive manner. Obesity is a side effect of cornstarch therapy, and appears to be associated with growth in these patients.

  14. Clinical implications of the intrinsic molecular subtypes of breast cancer.

    Science.gov (United States)

    Prat, Aleix; Pineda, Estela; Adamo, Barbara; Galván, Patricia; Fernández, Aranzazu; Gaba, Lydia; Díez, Marc; Viladot, Margarita; Arance, Ana; Muñoz, Montserrat

    2015-11-01

    Gene-expression profiling has had a considerable impact on our understanding of breast cancer biology. During the last 15 years, 5 intrinsic molecular subtypes of breast cancer (Luminal A, Luminal B, HER2-enriched, Basal-like and Claudin-low) have been identified and intensively studied. In this review, we will focus on the current and future clinical implications of the intrinsic molecular subtypes beyond the current pathological-based classification endorsed by the 2013 St. Gallen Consensus Recommendations. Within hormone receptor-positive and HER2-negative early breast cancer, the Luminal A and B subtypes predict 10-year outcome regardless of systemic treatment administered as well as residual risk of distant recurrence after 5 years of endocrine therapy. Within clinically HER2-positive disease, the 4 main intrinsic subtypes can be identified and dominate the biological and clinical phenotype. From a clinical perspective, patients with HER2+/HER2-enriched disease seem to benefit the most from neoadjuvant trastuzumab, or dual HER2 blockade with trastuzumab/lapatinib, in combination with chemotherapy, and patients with HER2+/Luminal A disease seem to have a relative better outcome compared to the other subtypes. Finally, within triple-negative breast cancer (TNBC), the Basal-like disease predominates (70-80%) and, from a biological perspective, should be considered a cancer-type by itself. Importantly, the distinction between Basal-like versus non-Basal-like within TNBC might predict survival following (neo)adjvuvant multi-agent chemotherapy, bevacizumab benefit in the neoadjuvant setting (CALGB40603), and docetaxel vs. carboplatin benefit in first-line metastatic disease (TNT study). Overall, this data suggests that intrinsic molecular profiling provides clinically relevant information beyond current pathology-based classifications.

  15. Synthetic lethality for linking the mycophenolate mofetil mode of action with molecular disease and drug profiles.

    Science.gov (United States)

    Söllner, Johannes; Mayer, Paul; Heinzel, Andreas; Fechete, Raul; Siehs, Christian; Oberbauer, Rainer; Mayer, Bernd

    2012-10-30

    Systematic study of the effect of mycophenolate mofetil (MMF) on the molecular level in the context of other drugs and molecular disease profiles became possible due to the availability of large scale molecular profiles on both disease characterization and drug mode of action. Such analysis is of particular value in elucidating alternative drug use for addressing clinically unmet needs, and the concept of synthetic lethality provides an alternative tool for such repositioning strategies. Resting on consolidation of transcriptomics data and literature mining, a MMF molecular footprint became available including a set of 170 genes specifically affected by the drug. Analysis of this profile on a molecular pathway level reveals a set of 14 pathways as affected. Next to assignment of molecular pathways and associated diseases synergistic drug combinations are proposed by utilizing the synthetic lethal interaction network. Of particular interest is the combination of MMF with adenosine deaminase inhibitors, sulfasalazine, and other selected drugs interfering with calcium-based regulatory pathways and metabolism. Indeed analysis of drugs in clinical trials positively identifies combinations with MMF in the context of synthetic lethality and affected pathways, particularly in diseases such as multiple sclerosis, vasculitis, GVHD and lupus nephritis. Importantly, the synthetic lethal interaction of the drug mode of action is an interesting basis for rational repositioning strategies by suggesting combinations which exhibit a synergistic rather than a mere additive effect, as for example is evident for the combination of tacrolimus and MMF. Inherent is also the assessment of possible adverse effects of drug combinations. PMID:23014771

  16. Clinical relevance of copy number profiling in oral and oropharyngeal squamous cell carcinoma

    NARCIS (Netherlands)

    van Kempen, Pauline M. W.; Noorlag, Rob; Braunius, Weibel W.; Moelans, Cathy B.; Rifi, Widad; Savola, Suvi; Koole, Ronald; Grolman, Wilko; van Es, RJJ; Willems, Stefan M.

    2015-01-01

    Current conventional treatment modalities in head and neck squamous cell carcinoma (HNSCC) are nonselective and have shown to cause serious side effects. Unraveling the molecular profiles of head and neck cancer may enable promising clinical applications that pave the road for personalized cancer tr

  17. Clinical profile of children with developmental delay and microcephaly

    OpenAIRE

    Anju Aggarwal; Hema Mittal; Rahul Patil; Sanjib Debnath; Anuradha Rai

    2013-01-01

    Aim: To study the profile of children with developmental delay and microcephaly. Materials and Methods: Children attending child development clinic with developmental delay were evaluated as per protocol. Z scores of head circumference were calculated using WHO charts. Clinical, radiological and etiological profile of those with microcephaly and those without was compared. Results: Of the 414 children with developmental delay 231 had microcephaly (z score ≤ -3). Mean age of children with micr...

  18. CLINICAL PROFILE OF ACUTE MYOCARDIAL INFARCTION YOUNG ADULTS

    OpenAIRE

    Patel G. N; Khandeparkar; Kotha; Cacodcar

    2015-01-01

    BACKGROUND : Although acute myocardial infarction was believed to be an uncommon entity in the young, of late there has been a rising incidence in this group of population. The analysis of its clinical profile, including the etiologic and the risk factors gains much importance, for the preventive purpose. AIMS AND OBJECTIVES: To study the clinical profile of acute MI, including the evaluation of the cardiac enzyme markers, the risk factors, the management and ...

  19. Molecular profiling of breast cancer: transcriptomic studies and beyond.

    Science.gov (United States)

    Culhane, A C; Howlin, J

    2007-12-01

    Utilisation of 'omics' technologies, in particular gene expression profiling, has increased dramatically in recent years. In basic research, high-throughput profiling applications are increasingly used and may now even be considered standard research tools. In the clinic, there is a need for better and more accurate diagnosis, prognosis and treatment response indicators. As such, clinicians have looked to omics technologies for potential biomarkers. These prediction profiling studies have in turn attracted the attention of basic researchers eager to uncover biological mechanisms underlying clinically useful signatures. Here we highlight some of the seminal work establishing the arrival of the omics, in particular transcriptomics, in breast cancer research and discuss a sample of the most current applications. We also discuss the challenges of data analysis and integrated data analysis with emphasis on utilising the current publicly available gene expression datasets. (Part of a Multi-author Review). PMID:17957338

  20. Gastric cancer-molecular and clinical dimensions.

    Science.gov (United States)

    Wadhwa, Roopma; Song, Shumei; Lee, Ju-Seog; Yao, Yixin; Wei, Qingyi; Ajani, Jaffer A

    2013-11-01

    Gastric cancer imposes a considerable health burden around the globe despite its declining incidence. The disease is often diagnosed in advanced stages and is associated with a poor prognosis for patients. An in-depth understanding of the molecular underpinnings of gastric cancer has lagged behind many other cancers of similar incidence and morbidity, owing to our limited knowledge of germline susceptibility traits for risk and somatic drivers of progression (to identify novel therapeutic targets). A few germline (PLCE1) and somatic (ERBB2, ERBB3, PTEN, PI3K/AKT/mTOR, FGF, TP53, CDH1 and MET) alterations are emerging and some are being pursued clinically. Novel somatic gene targets (ARID1A, FAT4, MLL and KMT2C) have also been identified and are of interest. Variations in the therapeutic approaches dependent on geographical region are evident for localized gastric cancer-differences that are driven by preferences for the adjuvant strategies and the extent of surgery coupled with philosophical divides. However, greater uniformity in approach has been noted in the metastatic cancer setting, an incurable condition. Having realized only modest successes, momentum is building for carrying out more phase III comparative trials, with some using biomarker-based patient selection strategies. Overall, rapid progress in biotechnology is improving our molecular understanding and can help with new drug discovery. The future prospects are excellent for defining biomarker-based subsets of patients and application of specific therapeutics. However, many challenges remain to be tackled. Here, we review representative molecular and clinical dimensions of gastric cancer.

  1. A CLINICAL PROFILE OF ACUTE POISONING

    Directory of Open Access Journals (Sweden)

    Vaddadi

    2015-04-01

    Full Text Available 100 patients were studied to know the common poisons, age, sex, clinical manifestations, response to treatment, motive behind the consumption and prognostic factors. Out of 100 cases, most of them committed this with suicidal intention, 21 - 30 age group, males, insecticide poison consumed were affected. 70% of them had domestic problems as the main reason to commit this extreme step. Those who reached early to the hospital had recovered well with a mortality rate of 7%.

  2. Estetrol review: profile and potential clinical applications.

    Science.gov (United States)

    Coelingh Bennink, H J T; Holinka, C F; Diczfalusy, E

    2008-01-01

    In this review paper, the existing information on the human fetal steroid estetrol (E4) has been summarized. In the past, E4 was considered as a weak estrogen and interest disappeared. However, recent new research has demonstrated that E4 is a potent, orally bioavailable, natural human fetal selective estrogen receptor modulator, since it acts in the rat as an estrogen on all tissues investigated except breast tumor tissue, where it has estrogen antagonistic properties in the presence of estradiol. Based on its safety data, its pharmacokinetic properties, its pharmacological profile and the results of first human studies, E4 may be suitable as a potential drug for human use in applications such as hormone replacement therapy (vaginal atrophy, hot flushes), contraception and osteoporosis. Additional areas worth exploring are the treatment of breast and prostate cancer, hypoactive sexual desire disorder and topical use (wrinkles) in women, auto-immune diseases, migraine, cardiovascular applications and the treatment of selected obstetric disorders. PMID:18464023

  3. CLINICAL PROFILE OF PATIENTS ATTENDING A PRISON PSYCHIATRIC CLINIC

    OpenAIRE

    R K Chadda; Amarjeet,

    1998-01-01

    Psychiatric morbidity is higher in prison inmates as compared to that in general population but treatment facilities are often inadequate. The present work reports the profile of psychiatric patients seen in a jail hospital over a period of three months. The jail had about 9000 inmates. Psychiatric services consisted of weekly visit by a psychiatrist. Seventy two male inmates were seen during the period of study. Most of them (80%) were undertrials. Diagnosis included schizophrenia, depressio...

  4. Clinical profile of patients with infantile spasms

    Directory of Open Access Journals (Sweden)

    Wael hayel khreisat

    2011-04-01

    Full Text Available Objective: The present study was done in order to obtain a baseline profile of infantile spasms and associated neurological disorders Patient and methods:. The study included 50 patients with infantile spasm in Queen Rania Hospital for children in Jordan. The following data were obtained: sex, age of onset and presentation, details of seizure , family history of epilepsy, significant pre-/peri/post-natal insults, neuro imaging evaluation , detailed neurological and neuro developmental ,assessment were done by. Broad categories of possible etiologies were used the results were recorded for further study. Results: Age of onset of infantile spasm ranged from 1month to 1 year and 6 months , (mean 4.8 months. The mean time of presentation was 9.4 months . A male preponderance was noted (74 %. flexor spasms (52% were the commonest. Other types of seizures also accompanied infantile spasm in 44% children. (84% were born of normal delivery, History of birth asphyxia was obtained in 48%, 3 (6% had positive family history Developmental delay was recognized prior to onset of spasms in 52% . microcephaly was the commonest associated problem , Imaging studies of the brain revealed abnormality in 18 patients. 78% patients symptomatic and 22 % as cryptogenic.. Conclusion: The pattern of infantile spasm in our country do not differ from that of developed countries, further researches is required to prevent both chronic epilepsy and psychomotor retardation and .preventive measurement to prevent birth asphyxia is recommended

  5. Clinical pharmacokinetic and pharmacodynamic profile of etoricoxib.

    Science.gov (United States)

    Takemoto, Jody K; Reynolds, Jonathan K; Remsberg, Connie M; Vega-Villa, Karina R; Davies, Neal M

    2008-01-01

    The NSAID etoricoxib is a selective inhibitor of cyclo-oxygenase 2 (COX-2), approved for treatment of patients with chronic arthropathies and musculoskeletal and dental pain. The rate of absorption of etoricoxib is moderate when given orally (the maximum plasma drug concentration occurs after approximately 1 hour), and the extent of absorption is similar with oral and intravenous doses. Etoricoxib is extensively protein bound, primarily to plasma albumin, and has an apparent volume of distribution of 120 L in humans. The area under the plasma concentration-time curve (AUC) of etoricoxib increases in proportion to increasing oral doses between 5 and 120 mg. The elimination half-life of approximately 20 hours in healthy subjects enables once-daily dosing. Etoricoxib is eliminated following biotransformation to carboxylic acid and glucuronide metabolites that are excreted in urine and faeces, with little of the drug (benefits and risks of etoricoxib compared with other options in the clinical arsenal. PMID:18840026

  6. Culture enriched molecular profiling of the cystic fibrosis airway microbiome.

    Science.gov (United States)

    Sibley, Christopher D; Grinwis, Margot E; Field, Tyler R; Eshaghurshan, Christina S; Faria, Monica M; Dowd, Scot E; Parkins, Michael D; Rabin, Harvey R; Surette, Michael G

    2011-01-01

    The microbiome of the respiratory tract, including the nasopharyngeal and oropharyngeal microbiota, is a dynamic community of microorganisms that is highly diverse. The cystic fibrosis (CF) airway microbiome refers to the polymicrobial communities present in the lower airways of CF patients. It is comprised of chronic opportunistic pathogens (such as Pseudomonas aeruginosa) and a variety of organisms derived mostly from the normal microbiota of the upper respiratory tract. The complexity of these communities has been inferred primarily from culture independent molecular profiling. As with most microbial communities it is generally assumed that most of the organisms present are not readily cultured. Our culture collection generated using more extensive cultivation approaches, reveals a more complex microbial community than that obtained by conventional CF culture methods. To directly evaluate the cultivability of the airway microbiome, we examined six samples in depth using culture-enriched molecular profiling which combines culture-based methods with the molecular profiling methods of terminal restriction fragment length polymorphisms and 16S rRNA gene sequencing. We demonstrate that combining culture-dependent and culture-independent approaches enhances the sensitivity of either approach alone. Our techniques were able to cultivate 43 of the 48 families detected by deep sequencing; the five families recovered solely by culture-independent approaches were all present at very low abundance (<0.002% total reads). 46% of the molecular signatures detected by culture from the six patients were only identified in an anaerobic environment, suggesting that a large proportion of the cultured airway community is composed of obligate anaerobes. Most significantly, using 20 growth conditions per specimen, half of which included anaerobic cultivation and extended incubation times we demonstrate that the majority of bacteria present can be cultured.

  7. Culture enriched molecular profiling of the cystic fibrosis airway microbiome.

    Directory of Open Access Journals (Sweden)

    Christopher D Sibley

    Full Text Available The microbiome of the respiratory tract, including the nasopharyngeal and oropharyngeal microbiota, is a dynamic community of microorganisms that is highly diverse. The cystic fibrosis (CF airway microbiome refers to the polymicrobial communities present in the lower airways of CF patients. It is comprised of chronic opportunistic pathogens (such as Pseudomonas aeruginosa and a variety of organisms derived mostly from the normal microbiota of the upper respiratory tract. The complexity of these communities has been inferred primarily from culture independent molecular profiling. As with most microbial communities it is generally assumed that most of the organisms present are not readily cultured. Our culture collection generated using more extensive cultivation approaches, reveals a more complex microbial community than that obtained by conventional CF culture methods. To directly evaluate the cultivability of the airway microbiome, we examined six samples in depth using culture-enriched molecular profiling which combines culture-based methods with the molecular profiling methods of terminal restriction fragment length polymorphisms and 16S rRNA gene sequencing. We demonstrate that combining culture-dependent and culture-independent approaches enhances the sensitivity of either approach alone. Our techniques were able to cultivate 43 of the 48 families detected by deep sequencing; the five families recovered solely by culture-independent approaches were all present at very low abundance (<0.002% total reads. 46% of the molecular signatures detected by culture from the six patients were only identified in an anaerobic environment, suggesting that a large proportion of the cultured airway community is composed of obligate anaerobes. Most significantly, using 20 growth conditions per specimen, half of which included anaerobic cultivation and extended incubation times we demonstrate that the majority of bacteria present can be cultured.

  8. Ricin Toxicity: Clinical and Molecular Aspects

    Science.gov (United States)

    Moshiri, Mohammad; Hamid, Fatemeh; Etemad, Leila

    2016-01-01

    Seeds of the castor bean plant Ricinuscommunis L (CB) contain ricin toxin (RT), one of the most poisonous naturally-occurring substances known. Ricin toxin, a water-soluble glycoprotein that does not partition into the oil extract, is a ribosome-inactivating toxin composed of two chains, labeled A and B. Severity of the toxicity varies depending on the route of exposure to the toxin. Inhalational is the most toxic route, followed by oral ingestion. Orally-ingested RT accumulates in the liver and spleen but other cells are also affected. The main clinical manifestations are also related to the administration route. Oral ingestion of CB or RT results in abdominal pain, vomiting, diarrhea, and various types of gastrointestinal bleeding that leading to volume depletion, hypovolemic shock, and renal failure. Inhalation of the toxin presents with non-cardiogenic pulmonary edema, diffuse necrotizing pneumonia, interstitial and alveolar inflammation, and edema. Local injection of RT induces indurations at the injection site, swelling of regional lymph nodes, hypotension, and death. An enzyme-linked immunosorbent assay (ELISA) has been developed to detect RT in animal tissues and fluids. Ricinine, an alkaloid of CB, can be detected in rat urine within 48 h of RT exposure. Supportive care is the basic treatment and standard biowarfare decontamination protocols are used for RT intoxication. Dexamethasone and difluoromethylornithine might be effective treatments. This review examines the clinical and molecular aspects of ricin toxicity. PMID:27536698

  9. Ricin Toxicity: Clinical and Molecular Aspects.

    Science.gov (United States)

    Moshiri, Mohammad; Hamid, Fatemeh; Etemad, Leila

    2016-04-01

    Seeds of the castor bean plant Ricinuscommunis L (CB) contain ricin toxin (RT), one of the most poisonous naturally-occurring substances known. Ricin toxin, a water-soluble glycoprotein that does not partition into the oil extract, is a ribosome-inactivating toxin composed of two chains, labeled A and B. Severity of the toxicity varies depending on the route of exposure to the toxin. Inhalational is the most toxic route, followed by oral ingestion. Orally-ingested RT accumulates in the liver and spleen but other cells are also affected. The main clinical manifestations are also related to the administration route. Oral ingestion of CB or RT results in abdominal pain, vomiting, diarrhea, and various types of gastrointestinal bleeding that leading to volume depletion, hypovolemic shock, and renal failure. Inhalation of the toxin presents with non-cardiogenic pulmonary edema, diffuse necrotizing pneumonia, interstitial and alveolar inflammation, and edema. Local injection of RT induces indurations at the injection site, swelling of regional lymph nodes, hypotension, and death. An enzyme-linked immunosorbent assay (ELISA) has been developed to detect RT in animal tissues and fluids. Ricinine, an alkaloid of CB, can be detected in rat urine within 48 h of RT exposure. Supportive care is the basic treatment and standard biowarfare decontamination protocols are used for RT intoxication. Dexamethasone and difluoromethylornithine might be effective treatments. This review examines the clinical and molecular aspects of ricin toxicity. PMID:27536698

  10. Ricin Toxicity: Clinical and Molecular Aspects

    Science.gov (United States)

    Moshiri, Mohammad; Hamid, Fatemeh; Etemad, Leila

    2016-01-01

    Seeds of the castor bean plant Ricinuscommunis L (CB) contain ricin toxin (RT), one of the most poisonous naturally-occurring substances known. Ricin toxin, a water-soluble glycoprotein that does not partition into the oil extract, is a ribosome-inactivating toxin composed of two chains, labeled A and B. Severity of the toxicity varies depending on the route of exposure to the toxin. Inhalational is the most toxic route, followed by oral ingestion. Orally-ingested RT accumulates in the liver and spleen but other cells are also affected. The main clinical manifestations are also related to the administration route. Oral ingestion of CB or RT results in abdominal pain, vomiting, diarrhea, and various types of gastrointestinal bleeding that leading to volume depletion, hypovolemic shock, and renal failure. Inhalation of the toxin presents with non-cardiogenic pulmonary edema, diffuse necrotizing pneumonia, interstitial and alveolar inflammation, and edema. Local injection of RT induces indurations at the injection site, swelling of regional lymph nodes, hypotension, and death. An enzyme-linked immunosorbent assay (ELISA) has been developed to detect RT in animal tissues and fluids. Ricinine, an alkaloid of CB, can be detected in rat urine within 48 h of RT exposure. Supportive care is the basic treatment and standard biowarfare decontamination protocols are used for RT intoxication. Dexamethasone and difluoromethylornithine might be effective treatments. This review examines the clinical and molecular aspects of ricin toxicity.

  11. Dengue in HIV infected patients:clinical profiles

    Institute of Scientific and Technical Information of China (English)

    Beuy Joob; Viroj Wiwanitkit

    2014-01-01

    Dengue is an important tropical viral infection. It can present with acute febrile illness with possible hemorrhagic complication. Since it is a common infection in the tropical world, concomitance with other diseases can be expected. An important consideration is the co-presentation of dengue with HIV infection. In this specific report, the authors summarize the clinical profiles of dengue patients with HIV infection. Based on the present study, it can be seen that clinical profiles of dengue in any group of HIV infection is not different.

  12. Molecular profiling in the treatment of colorectal cancer: focus on regorafenib

    Directory of Open Access Journals (Sweden)

    Yan Y

    2015-10-01

    Full Text Available Yiyi Yan, Axel Grothey Department of Medical Oncology, Mayo Clinic, Rochester, MN, USA Abstract: Metastatic colorectal cancer (mCRC is a highly heterogeneous disease. Its treatment outcome has been significantly improved over the last decade with the incorporation of biological targeted therapies, including anti-EGFR antibodies, cetuximab and panitumumab, and VEGF inhibitors, bevacizumab, ramucirumab, and aflibercept. The identification of predictive biomarkers has further improved the survival by accurately selecting patients who are most likely to benefit from these treatments, such as RAS mutation profiling for EGFR antibodies. Regorafenib is a multikinase inhibitor currently used as late line therapy for mCRC. The molecular and genetic markers associated with regorafenib treatment response are yet to be characterized. Here, we review currently available clinical evidence of mCRC molecular profiling, such as RAS, BRAF, and MMR testing, and its role in targeted therapies with special focus on regorafenib treatment. Keywords: metastatic colon cancer, targeted therapy, molecular profiling, regorafenib 

  13. Infantile and early childhood masturbation: Sex hormones and clinical profile

    OpenAIRE

    2010-01-01

    BACKGROUND AND OBJECTIVES: Few studies have explored the hormonal triggers for masturbation in infants and young children. Thus, we aimed to study the sex hormones and clinical profiles of masturbating infants and young children. METHODS: This case-control study involved infants and young children who masturbate and were referred to three pediatric neurology clinics between September 2004 and 2006 (n=13), and a similar control group. All children underwent basic laboratory investigations prio...

  14. Molecular Profiling Reveals Biologically Discrete Subsets and Pathways of Progression in Diffuse Glioma.

    Science.gov (United States)

    Ceccarelli, Michele; Barthel, Floris P; Malta, Tathiane M; Sabedot, Thais S; Salama, Sofie R; Murray, Bradley A; Morozova, Olena; Newton, Yulia; Radenbaugh, Amie; Pagnotta, Stefano M; Anjum, Samreen; Wang, Jiguang; Manyam, Ganiraju; Zoppoli, Pietro; Ling, Shiyun; Rao, Arjun A; Grifford, Mia; Cherniack, Andrew D; Zhang, Hailei; Poisson, Laila; Carlotti, Carlos Gilberto; Tirapelli, Daniela Pretti da Cunha; Rao, Arvind; Mikkelsen, Tom; Lau, Ching C; Yung, W K Alfred; Rabadan, Raul; Huse, Jason; Brat, Daniel J; Lehman, Norman L; Barnholtz-Sloan, Jill S; Zheng, Siyuan; Hess, Kenneth; Rao, Ganesh; Meyerson, Matthew; Beroukhim, Rameen; Cooper, Lee; Akbani, Rehan; Wrensch, Margaret; Haussler, David; Aldape, Kenneth D; Laird, Peter W; Gutmann, David H; Noushmehr, Houtan; Iavarone, Antonio; Verhaak, Roel G W

    2016-01-28

    Therapy development for adult diffuse glioma is hindered by incomplete knowledge of somatic glioma driving alterations and suboptimal disease classification. We defined the complete set of genes associated with 1,122 diffuse grade II-III-IV gliomas from The Cancer Genome Atlas and used molecular profiles to improve disease classification, identify molecular correlations, and provide insights into the progression from low- to high-grade disease. Whole-genome sequencing data analysis determined that ATRX but not TERT promoter mutations are associated with increased telomere length. Recent advances in glioma classification based on IDH mutation and 1p/19q co-deletion status were recapitulated through analysis of DNA methylation profiles, which identified clinically relevant molecular subsets. A subtype of IDH mutant glioma was associated with DNA demethylation and poor outcome; a group of IDH-wild-type diffuse glioma showed molecular similarity to pilocytic astrocytoma and relatively favorable survival. Understanding of cohesive disease groups may aid improved clinical outcomes. PMID:26824661

  15. Molecular mechanisms in muscular dystrophy: a gene expression profiling study.

    OpenAIRE

    Turk, Rolf

    2006-01-01

    The muscular dystrophies are a group of neuromuscular disorders characterized by progres¬sive muscle weakness and wasting. Although the underlying genetic defects of a large number of muscular dystrophies are now know, the molecular mechanisms resulting in the devastating effects of the disease are not yet clear. Furthermore, the muscular dystrophies differ in clinical presentation and severity. The processes responsible for this di¬vergence are largely unknown as well. In this thesis, gene e...

  16. Clinical dosimetry in molecular radiotherapy: protocol optimization and clinical implementation

    International Nuclear Information System (INIS)

    Molecular radiotherapy (mrt) consists in destructing tumour targets by radiolabelled vectors. This nuclear medicine specialty is being considered with increasing interest for example via the success achieved in the treatment of non-Hodgkin lymphomas by radioimmunotherapy. One of the keys of mrt optimization relies on the personalising of absorbed doses delivered to the patient: This is required to ascertain that irradiation is focused on tumour cells while keeping surrounding healthy tissue irradiation at an acceptable - non-toxic - level. Radiation dose evaluation in mrt requires in one hand, the spatial and temporal localization of injected radioactive sources by scintigraphic imaging, and on a second hand, the knowledge of the emitted radiation propagating media, given by CT imaging. Global accuracy relies on the accuracy of each of the steps that contribute to clinical dosimetry. There is no reference, standardized dosimetric protocol to date. Due to heterogeneous implementations, evaluation of the accuracy of the absorbed dose is a difficult task. In this thesis, we developed and evaluated different dosimetric approaches that allow us to find a relationship between the absorbed dose to the bone marrow and haematological toxicity. Besides, we built a scientific project, called DosiTest, which aims at evaluating the impact of the various step that contribute to the realization of a dosimetric study, by means of a virtual multicentric comparison based on Monte-Carlo modelling. (author)

  17. Assessing the Accuracy of Quantitative Molecular Microbial Profiling

    Directory of Open Access Journals (Sweden)

    Denise M. O'Sullivan

    2014-11-01

    Full Text Available The application of high-throughput sequencing in profiling microbial communities is providing an unprecedented ability to investigate microbiomes. Such studies typically apply one of two methods: amplicon sequencing using PCR to target a conserved orthologous sequence (typically the 16S ribosomal RNA gene or whole (metagenome sequencing (WGS. Both methods have been used to catalog the microbial taxa present in a sample and quantify their respective abundances. However, a comparison of the inherent precision or bias of the different sequencing approaches has not been performed. We previously developed a metagenomic control material (MCM to investigate error when performing different sequencing strategies. Amplicon sequencing using four different primer strategies and two 16S rRNA regions was examined (Roche 454 Junior and compared to WGS (Illumina HiSeq. All sequencing methods generally performed comparably and in good agreement with organism specific digital PCR (dPCR; WGS notably demonstrated very high precision. Where discrepancies between relative abundances occurred they tended to differ by less than twofold. Our findings suggest that when alternative sequencing approaches are used for microbial molecular profiling they can perform with good reproducibility, but care should be taken when comparing small differences between distinct methods. This work provides a foundation for future work comparing relative differences between samples and the impact of extraction methods. We also highlight the value of control materials when conducting microbial profiling studies to benchmark methods and set appropriate thresholds.

  18. Clinical, biochemical and molecular characterization of prosaposin deficiency.

    Science.gov (United States)

    Motta, M; Tatti, M; Furlan, F; Celato, A; Di Fruscio, G; Polo, G; Manara, R; Nigro, V; Tartaglia, M; Burlina, A; Salvioli, R

    2016-09-01

    Prosaposin (PSAP) deficiency is an ultra-rare, fatal infantile lysosomal storage disorder (LSD) caused by variants in the PSAP gene, with seven subjects reported so far. Here, we provide the clinical, biochemical and molecular characterization of two additional PSAP deficiency cases. Lysoplex, a targeted resequencing approach was utilized to identify the variant in the first patient, while quantification of plasma lysosphingolipids (lysoSLs), assessed by liquid chromatography mass spectrometry (LC-MS/MS) and brain magnetic resonance imaging (MRI), followed by Sanger sequencing allowed to attain diagnosis in the second case. Functional studies were carried out on patients' fibroblast lines to explore the functional impact of variants. The two patients were homozygous for two different truncating PSAP mutations (c.895G>T, p.Glu299*; c.834_835delGA, p.Glu278Aspfs*27). Both variants led to a complete lack of processed transcript. LC-MS/MS and brain MRI analyses consistently provided a distinctive profile in the two children. Quantification of specific plasma lysoSLs revealed elevated levels of globotriaosylsphingosine (LysoGb3) and glucosylsphingosine (GlSph), and accumulation of autophagosomes, due to a decreased autophagic flux, was observed. This report documents the successful use of plasma lysoSLs profiling in the PSAP deficiency diagnosis, as a reliable and informative tool to obtain a preliminary information in infantile cases with complex traits displaying severe neurological signs and visceral involvement. PMID:26831127

  19. PHENOTYPIC INVESTIGATION OF VIRULENCE PROFILES IN SOME CANDIDA SPP. STRAINS ISOLATED FROM DIFFERENT CLINICAL SPECIMENS

    Directory of Open Access Journals (Sweden)

    Alina Maria Holban

    2012-09-01

    Full Text Available Candida species great versatility may explain their wide range of infections occurred in a great variety of hosts. Even though many modern molecular techniques arise, phenotypic assays still provide valuable information and can guide the diagnosis and the treatment of infections. The phenotypic investigation of virulence determinants in some recent nosocomial isolates of Candida spp. revealed that the fungal clinical strains may develop specific virulence profiles depending on the taxonomic affiliation of the tested strains and the source of infection. Our data support the usefulness of phenotypic assays in predicting the clinical outcome of the fungal infections and in the adjustment of the antifungal treatment.

  20. Health profiles of foreigners attending primary care clinics in Malaysia

    OpenAIRE

    Ab Rahman, Norazida; Sivasampu, Sheamini; Mohamad Noh, Kamaliah; Khoo, Ee Ming

    2016-01-01

    Background The world population has become more globalised with increasing number of people residing in another country for work or other reasons. Little is known about the health profiles of foreign population in Malaysia. The aim of this study was to provide a detailed description of the health problems presented by foreigners attending primary care clinics in Malaysia. Methods Data were derived from the 2012 National Medical Care Survey (NMCS), a cross sectional survey of primary care enco...

  1. Clinical profile of forefoot eczema: A study of 42 cases

    OpenAIRE

    Brar Kamal; Shenoi S; Balachandran C; Mehta Vandana

    2005-01-01

    BACKGROUND : Forefoot eczema (FE) is characterized by dry fissured dermatitis of the plantar surface of the feet. AIM : To study the clinical profile of FE and the possible etiological factors. METHODS : Forty-two patients with FE were included in the study. A detailed history was recorded and examination done. Fungal scrapings and patch test with Indian Standard Series (ISS) were performed in all patients. RESULTS : The most common site affected was the plantar surface of the great toe in...

  2. DNA methylation profiles delineate etiologic heterogeneity and clinically important subgroups of bladder cancer.

    Science.gov (United States)

    Wilhelm-Benartzi, C S; Koestler, D C; Houseman, E A; Christensen, B C; Wiencke, John K; Schned, A R; Karagas, M R; Kelsey, K T; Marsit, C J

    2010-11-01

    DNA methylation profiles can be used to define molecular cancer subtypes that may better inform disease etiology and clinical decision-making. This investigation aimed to create DNA methylation profiles of bladder cancer based on CpG methylation from almost 800 cancer-related genes and to then examine the relationship of those profiles with exposures related to risk and clinical characteristics. DNA, derived from formalin-fixed paraffin-embedded tumor samples obtained from incident cases involved in a population-based case-control study of bladder cancer in New Hampshire, was used for methylation profiling on the Illumina GoldenGate Methylation Bead Array. Unsupervised clustering of those loci with the greatest change in methylation between tumor and non-diseased tissue was performed to defined molecular subgroups of disease, and univariate tests of association followed by multinomial logistic regression was used to examine the association between these classes, bladder cancer risk factors and clinical phenotypes. Membership in the two most methylated classes was significantly associated with invasive disease (P class 3 and 4). Male gender (P = 0.04) and age >70 years (P = 0.05) was associated with membership in one of the most methylated classes. Finally, average water arsenic levels in the highest percentile predicted membership in an intermediately methylated class of tumors (P = 0.02 for both classes). Exposures and demographic associated with increased risk of bladder cancer specifically associate with particular subgroups of tumors defined by DNA methylation profiling and these subgroups may define more aggressive disease.

  3. Molecular profiling of dilated cardiomyopathy that progresses to heart failure

    Science.gov (United States)

    Burke, Michael A.; Chang, Stephen; Wakimoto, Hiroko; Gorham, Joshua M.; Conner, David A.; Christodoulou, Danos C.; Parfenov, Michael G.; DePalma, Steve R.; Eminaga, Seda; Konno, Tetsuo; Seidman, Jonathan G.; Seidman, Christine E.

    2016-01-01

    Dilated cardiomyopathy (DCM) is defined by progressive functional and structural changes. We performed RNA-seq at different stages of disease to define molecular signaling in the progression from pre-DCM hearts to DCM and overt heart failure (HF) using a genetic model of DCM (phospholamban missense mutation, PLNR9C/+). Pre-DCM hearts were phenotypically normal yet displayed proliferation of nonmyocytes (59% relative increase vs. WT, P = 8 × 10–4) and activation of proinflammatory signaling with notable cardiomyocyte-specific induction of a subset of profibrotic cytokines including TGFβ2 and TGFβ3. These changes progressed through DCM and HF, resulting in substantial fibrosis (17.6% of left ventricle [LV] vs. WT, P = 6 × 10–33). Cardiomyocytes displayed a marked shift in metabolic gene transcription: downregulation of aerobic respiration and subsequent upregulation of glucose utilization, changes coincident with attenuated expression of PPARα and PPARγ coactivators -1α (PGC1α) and -1β, and increased expression of the metabolic regulator T-box transcription factor 15 (Tbx15). Comparing DCM transcriptional profiles with those in hypertrophic cardiomyopathy (HCM) revealed similar and distinct molecular mechanisms. Our data suggest that cardiomyocyte-specific cytokine expression, early fibroblast activation, and the shift in metabolic gene expression are hallmarks of cardiomyopathy progression. Notably, key components of these profibrotic and metabolic networks were disease specific and distinguish DCM from HCM. PMID:27239561

  4. HCC Heterogeneity: Molecular Pathogenesis and Clinical Implications

    Directory of Open Access Journals (Sweden)

    Emilia Fransvea

    2009-01-01

    Full Text Available Background: Hepatocellular carcinoma (HCC poses a major challenge because of the extreme variability of the clinical outcome, which makes it difficult to properly stage the disease and thereby estimate the prognosis. There is growing evidence that this heterogeneous clinical behavior is attributable to several different biological pathways. A novel approach to mapping these differences is by investigating the epigenetics associated with certain clinical aspects.

  5. Prognosis related clinical and molecular factors in malignant pleural mesothelioma

    Institute of Scientific and Technical Information of China (English)

    王玉艳

    2013-01-01

    Objective To identify potential prognosis related clinical and molecular factors in malignant pleural mesothelioma(MPM).Methods Seventy-nine patients with MPM treated in Beijing Cancer Hospital from June 1996

  6. Molecular Dimensions of Gastric Cancer: Translational and Clinical Perspectives.

    Science.gov (United States)

    Choi, Yoon Young; Noh, Sung Hoon; Cheong, Jae-Ho

    2016-01-01

    Gastric cancer is a global health burden and has the highest incidence in East Asia. This disease is complex in nature because it arises from multiple interactions of genetic, local environmental, and host factors, resulting in biological heterogeneity. This genetic intricacy converges on molecular characteristics reflecting the pathophysiology, tumor biology, and clinical outcome. Therefore, understanding the molecular characteristics at a genomic level is pivotal to improving the clinical care of patients with gastric cancer. A recent landmark study, The Cancer Genome Atlas (TCGA) project, showed the molecular landscape of gastric cancer through a comprehensive molecular evaluation of 295 primary gastric cancers. The proposed molecular classification divided gastric cancer into four subtypes: Epstein-Barr virus-positive, microsatellite unstable, genomic stable, and chromosomal instability. This information will be taken into account in future clinical trials and will be translated into clinical therapeutic decisions. To fully realize the clinical benefit, many challenges must be overcome. Rapid growth of high-throughput biology and functional validation of molecular targets will further deepen our knowledge of molecular dimensions of this cancer, allowing for personalized precision medicine. PMID:26498010

  7. Identification of a Myometrial Molecular Profile for Dystocic Labor

    LENUS (Irish Health Repository)

    Brennan, Donal J

    2011-10-16

    Abstract Background The most common indication for cesarean section (CS) in nulliparous women is dystocia secondary to ineffective myometrial contractility. The aim of this study was to identify a molecular profile in myometrium associated with dystocic labor. Methods Myometrial biopsies were obtained from the upper incisional margins of nulliparous women undergoing lower segment CS for dystocia (n = 4) and control women undergoing CS in the second stage who had demonstrated efficient uterine action during the first stage of labor (n = 4). All patients were in spontaneous (non-induced) labor and had received intrapartum oxytocin to accelerate labor. RNA was extracted from biopsies and hybridized to Affymetrix HuGene U133A Plus 2 microarrays. Internal validation was performed using quantitative SYBR Green Real-Time PCR. Results Seventy genes were differentially expressed between the two groups. 58 genes were down-regulated in the dystocia group. Gene ontology analysis revealed 12 of the 58 down-regulated genes were involved in the immune response. These included (ERAP2, (8.67 fold change (FC)) HLA-DQB1 (7.88 FC) CD28 (2.60 FC), LILRA3 (2.87 FC) and TGFBR3 (2.1 FC)) Hierarchical clustering demonstrated a difference in global gene expression patterns between the samples from dystocic and non-dystocic labours. RT-PCR validation was performed on 4 genes ERAP2, CD28, LILRA3 and TGFBR3 Conclusion These findings suggest an underlying molecular basis for dystocia in nulliparous women in spontaneous labor. Differentially expressed genes suggest an important role for the immune response in dystocic labor and may provide important indicators for new diagnostic assays and potential intrapartum therapeutic targets.

  8. Molecular profiling of angiogenesis in hypericin mediated photodynamic therapy

    Directory of Open Access Journals (Sweden)

    Ali Seyed M

    2008-06-01

    Full Text Available Abstract Background Photodynamic therapy (PDT involves the administration of a tumor-localizing photosensitizing drug, which is activated by light of specific wavelength in the presence of molecular oxygen thus generating reactive oxygen species that is toxic to the tumor cells. PDT selectively destroys photosensitized tissue leading to various cellular and molecular responses. The present study was designed to examine the angiogenic responses at short (0.5 h and long (6 h drug light interval (DLI hypericin-PDT (HY-PDT treatment at 24 h and 30 days post treatment in a human bladder carcinoma xenograft model. As short DLI targets tumor vasculature and longer DLI induces greater cellular damage, we hypothesized a differential effect of these treatments on the expression of angiogenic factors. Results Immunohistochemistry (IHC results showed minimal CD31 stained endothelium at 24 h post short DLI PDT indicating extensive vascular damage. Angiogenic proteins such as vascular endothelial growth factor (VEGF, tumor necrosis growth factor-α (TNF-α, interferon-α (IFN-α and basic fibroblast growth factor (bFGF were expressed to a greater extent in cellular targeting long DLI PDT compared to vascular mediated short DLI PDT. Gene expression profiling for angiogenesis pathway demonstrated downregulation of adhesion molecules – cadherin 5, collagen alpha 1 and 3 at 24 h post treatment. Hepatocyte growth factor (HGF and Ephrin-A3 (EFNA3 were upregulated in all treatment groups suggesting a possible activation of c-Met and Ephrin-Eph signaling pathways. Conclusion In conclusion, long DLI HY-PDT induces upregulation of angiogenic proteins. Differential expression of genes involved in the angiogenesis pathway was observed in the various groups treated with HY-PDT.

  9. Identification of a myometrial molecular profile for dystocic labor

    Directory of Open Access Journals (Sweden)

    O'Connor Darran P

    2011-10-01

    Full Text Available Abstract Background The most common indication for cesarean section (CS in nulliparous women is dystocia secondary to ineffective myometrial contractility. The aim of this study was to identify a molecular profile in myometrium associated with dystocic labor. Methods Myometrial biopsies were obtained from the upper incisional margins of nulliparous women undergoing lower segment CS for dystocia (n = 4 and control women undergoing CS in the second stage who had demonstrated efficient uterine action during the first stage of labor (n = 4. All patients were in spontaneous (non-induced labor and had received intrapartum oxytocin to accelerate labor. RNA was extracted from biopsies and hybridized to Affymetrix HuGene U133A Plus 2 microarrays. Internal validation was performed using quantitative SYBR Green Real-Time PCR. Results Seventy genes were differentially expressed between the two groups. 58 genes were down-regulated in the dystocia group. Gene ontology analysis revealed 12 of the 58 down-regulated genes were involved in the immune response. These included (ERAP2, (8.67 fold change (FC HLA-DQB1 (7.88 FC CD28 (2.60 FC, LILRA3 (2.87 FC and TGFBR3 (2.1 FC Hierarchical clustering demonstrated a difference in global gene expression patterns between the samples from dystocic and non-dystocic labours. RT-PCR validation was performed on 4 genes ERAP2, CD28, LILRA3 and TGFBR3 Conclusion These findings suggest an underlying molecular basis for dystocia in nulliparous women in spontaneous labor. Differentially expressed genes suggest an important role for the immune response in dystocic labor and may provide important indicators for new diagnostic assays and potential intrapartum therapeutic targets.

  10. Antimicrobial sensitivity profile of Staphylococcus spp. Isolated from clinical mastitis

    Directory of Open Access Journals (Sweden)

    Thamires Martins

    2012-12-01

    Full Text Available Inflammation of the mammary gland, which is also known as mastitis, occupies a prominent place among the diseases that affect dairy cattle, having a great economic importance in the dairy sector. Mastitis may have different origins, however, infectious mastitis is the most frequent and represents a risk to public health due to the propagation of microorganisms through milk. Staphylococcus spp. are considered the microorganisms that cause the greatest losses in milk production, being that Staphylococcus aureus is the pathogen of major importance because they present high resistence to antimicrobials. Empirical treatment, without prior identification of the pathogens and their resistance profile, may contribute to the emergence of multidrug-resistant strains and risk the efficiency of the antimicrobial. In that scenery, the study aimed to evaluate the resistance profile of Staphylococcus spp. against some antimicrobials used in the treatment of cows with clinical mastitis. The study was conducted on a property in the state of São Paulo from January 2011 to June 2012. We evaluated 29 lactating cows that present clinical mastitis in, at least, one mammary quarter. The diagnosis of clinical mastitis was performed by evaluating the clinical signs and also by Tamis test. Samples of milk from mammary quarters were collected aseptically in sterile tubes for microbiological evaluation. Microorganisms were isolated on sheep blood agar 5% and Sabouraud agar with chloramphenicol. The sensitivity profile of Staphylococcus spp. to the antibiotics ampicillin, cephalexin, ceftiofur, cefaclor, gentamicin, kanamycin, neomycin, penicillin G and oxacillin, was tested by disk diffusion test on Mueller-Hinton agar. From a total of 106 samples of milk analyzed, 64 (60.38% presented microbiological growth, being observed isolation of Streptococcus spp. 29 (34.52%, Staphylococcus spp. 28 (33.33%, Corynebacterium spp. 17 (20.24%, filamentous fungi 4 (4.76%, yeast 4 (4

  11. Metabolite profiling of CHO cells: Molecular reflections of bioprocessing effectiveness.

    Science.gov (United States)

    Sellick, Christopher A; Croxford, Alexandra S; Maqsood, Arfa R; Stephens, Gill M; Westerhoff, Hans V; Goodacre, Royston; Dickson, Alan J

    2015-09-01

    Whilst development of medium and feeds has provided major advances in recombinant protein production in CHO cells, the fundamental understanding is limited. We have applied metabolite profiling with established robust (GC-MS) analytics to define the molecular loci by which two yield-enhancing feeds improve recombinant antibody yields from a model GS-CHO cell line. With data across core metabolic pathways, that report on metabolism within several cellular compartments, these data identify key metabolites and events associated with increased cell survival and specific productivity of cells. Of particular importance, increased process efficiency was linked to the functional activity of the mitochondria, with the amount and time course of use/production of intermediates of the citric acid cycle, for uses such as lipid biosynthesis, precursor generation and energy production, providing direct indicators of cellular status with respect to productivity. The data provide clear association between specific cellular metabolic indicators and cell process efficiency, extending from prior indications of the relevance of lactate metabolic balance to other redox sinks (glycerol, sorbitol and threitol). The information, and its interpretation, identifies targets for engineering cell culture efficiency, either from genetic or environmental perspectives, and greater understanding of the significance of specific medium components towards overall CHO cell bioprocessing. PMID:26198903

  12. Study Of Clinical Profile of Allergic Contact Dermatitis In Pune

    Directory of Open Access Journals (Sweden)

    Sayal S K

    1999-01-01

    Full Text Available One hundred and twenty five cases of clinically diagnosed allergic contact dermatitis were studied. All patients were subjected to patch test with standard test allergens and also with suspected test allergens based on history and clinical profile. Allergic contact dermatitis due to Parthenium hysterophorus was commonest and found in 64% cases, followed by wearing apparel and jewellery in 16.8%, topical medicaments in 8% and cosmetics and occupational contactants in 5.6% cases each. The common individual allergens other than parthenium, were nickel in 8.8%, leather, hair dye and cement in 3.2% each, nitrofurazone and petrol, oil, lubricant (POL in 2.4% each. Patch test with suspected allergens was positive in 72% of cases.

  13. Clinical Profile & Risk Factors in Acute Coronary Syndrome

    Directory of Open Access Journals (Sweden)

    P Yadav, D Joseph, P Joshi, P Sakhi, RK Jha, J Gupta

    2010-12-01

    Full Text Available Coronary Artery Disease (CAD is becoming a major cause of morbidity & mortality burden in the developing world. Indians have been associated with a more severe form of CAD that has its onset at a younger age group with a male predominance. A prospective study was carried out to identify the risk factors and to know the emerging clinical profile in acute coronary syndrome (ACS including S T elevation & Non S T elevation myocardial infarction. We enrolled 200 consecutive patients with typical ECG changes & clinical history, admitted in emergency department from January 2009 to December 2009. A predefined Performa was completed in every patient with a detailed clinical history, physical examinations, and investigation studies. The clinical history revealed information about age, gender, risk factors, and modes of presentation and duration of symptoms. The details of physical examination including anthropometric data, vital signs and complete systemic evaluation were recorded. The regions of infarction and rhythm disturbances were also documented. Our study showed a significant male predominance with mean age being 56 years. Tobacco was identified as major risk factors (65% & obesity (BMI more than 25 is least common risk factor (13%.Patients had typical chest pain (94% and ECG showed anterior wall changes in54%. Forty percent patients developed complications, majority being arrhythmias (60% and least common is mechanical complication (2.5% Thus we conclude that ACS is more common in adult male with tobacco being major risk factors in our population.

  14. Molecular Expression Profile Reveals Potential Biomarkers and Therapeutic Targets in Canine Endometrial Lesions.

    Science.gov (United States)

    Voorwald, Fabiana Azevedo; Marchi, Fabio Albuquerque; Villacis, Rolando Andre Rios; Alves, Carlos Eduardo Fonseca; Toniollo, Gilson Hélio; Amorim, Renee Laufer; Drigo, Sandra Aparecida; Rogatto, Silvia Regina

    2015-01-01

    Cystic endometrial hyperplasia (CEH), mucometra, and pyometra are common uterine diseases in intact dogs, with pyometra being a life threatening disease. This study aimed to determine the gene expression profile of these lesions and potential biomarkers for closed-cervix pyometra, the most severe condition. Total RNA was extracted from 69 fresh endometrium samples collected from 21 healthy female dogs during diestrus, 16 CEH, 15 mucometra and 17 pyometra (eight open and nine closed-cervixes). Global gene expression was detected using the Affymetrix Canine Gene 1.0 ST Array. Unsupervised analysis revealed two clusters, one mainly composed of diestrus and CEH samples and the other by 12/15 mucometra and all pyometra samples. When comparing pyometra with other groups, 189 differentially expressed genes were detected. SLPI, PTGS2/COX2, MMP1, S100A8, S100A9 and IL8 were among the top up-regulated genes detected in pyometra, further confirmed by external expression data. Notably, a particular molecular profile in pyometra from animals previously treated with exogenous progesterone compounds was observed in comparison with pyometra from untreated dogs as well as with other groups irrespective of exogenous hormone treatment status. In addition to S100A8 and S100A9 genes, overexpression of the inflammatory cytokines IL1B, TNF and IL6 as well as LTF were detected in the pyometra from treated animals. Interestingly, closed pyometra was more frequently detected in treated dogs (64% versus 33%), with IL1B, TNF, LBP and CXCL10 among the most relevant overexpressed genes. This molecular signature associated with potential biomarkers and therapeutic targets, such as CXCL10 and COX2, should guide future clinical studies. Based on the gene expression profile we suggested that pyometra from progesterone treated dogs is a distinct molecular entity. PMID:26222498

  15. Molecular Expression Profile Reveals Potential Biomarkers and Therapeutic Targets in Canine Endometrial Lesions.

    Directory of Open Access Journals (Sweden)

    Fabiana Azevedo Voorwald

    Full Text Available Cystic endometrial hyperplasia (CEH, mucometra, and pyometra are common uterine diseases in intact dogs, with pyometra being a life threatening disease. This study aimed to determine the gene expression profile of these lesions and potential biomarkers for closed-cervix pyometra, the most severe condition. Total RNA was extracted from 69 fresh endometrium samples collected from 21 healthy female dogs during diestrus, 16 CEH, 15 mucometra and 17 pyometra (eight open and nine closed-cervixes. Global gene expression was detected using the Affymetrix Canine Gene 1.0 ST Array. Unsupervised analysis revealed two clusters, one mainly composed of diestrus and CEH samples and the other by 12/15 mucometra and all pyometra samples. When comparing pyometra with other groups, 189 differentially expressed genes were detected. SLPI, PTGS2/COX2, MMP1, S100A8, S100A9 and IL8 were among the top up-regulated genes detected in pyometra, further confirmed by external expression data. Notably, a particular molecular profile in pyometra from animals previously treated with exogenous progesterone compounds was observed in comparison with pyometra from untreated dogs as well as with other groups irrespective of exogenous hormone treatment status. In addition to S100A8 and S100A9 genes, overexpression of the inflammatory cytokines IL1B, TNF and IL6 as well as LTF were detected in the pyometra from treated animals. Interestingly, closed pyometra was more frequently detected in treated dogs (64% versus 33%, with IL1B, TNF, LBP and CXCL10 among the most relevant overexpressed genes. This molecular signature associated with potential biomarkers and therapeutic targets, such as CXCL10 and COX2, should guide future clinical studies. Based on the gene expression profile we suggested that pyometra from progesterone treated dogs is a distinct molecular entity.

  16. STUDY OF RISK FACTORS AND CLINICAL PROFILE OF ACUTE STROKE

    Directory of Open Access Journals (Sweden)

    Tomar

    2014-05-01

    Full Text Available `INTRODUCTION: Stroke is the third leading cause of death in developed countries after cardiovascular disease and cancer. In India Community Surveys have shown a crude prevalence rate for hemiplegia 200 per 1, 00, 000 population. It accounts for nearly 1.5% of all urban admissions, 4.5 % of all medical and about 20% of neurological cases. AIMS AND OBJECTIVE: Identification of risk factors and evaluation of clinical profile of acute stroke. MATERIAL AND METHOD: INCLUSION CRITERIA: Cases of acute stoke admitted in SGMH hospital were selected for the study. EXCLUSION CRITERIA: Brain injury cases, infective, neoplastic cases producing stroke were excluded. RESULTS: Stroke was more common in male, 58 % patients were male and 42% patients were female. It was more common in 5th and 6th decade. Most common etiology was infarction. Most common risk factor was hypertension followed by smoking. In addition to limb weakness, headache and vomiting were most common presenting symptoms followed by convulsion. These symptoms were more common in hemorrhagic stroke. Right sided hemiplegia was more common than left sided. Middle cerebral artery was involved in majority of cases in atherothrombotic stroke whereas basal ganglion was most common site of bleed in hemorrhagic stroke. Coma and mortality were more in hemorrhagic stroke. CONCLUSION: The risk factors and clinical profile of acute stroke in India are similar to that of Western countries. Common risk factors are hypertension, smoking, diabetes mellitus and hyperlipidemia

  17. Clinical and molecular research of neuroacanthocytosis

    Institute of Scientific and Technical Information of China (English)

    Lihong Zhang; Suping Wang; Jianwen Lin

    2013-01-01

    Neuroacanthocytosis is an autosomal recessive or dominant inherited disease characterized by widespread, non-specific nervous system symptoms, or spiculated "acanthocytic" red blood cells. The clinical manifestations typically involve chorea and dystonia, or a range of other movement disorders. Psychiatric and cognitive symptoms may also be present. The two core neuroacanthocytosis syndromes, in which acanthocytosis is atypical, are autosomal recessive chorea-acanthocytosis and X-linked McLeod syndrome. Acanthocytes are found in a smaller proportion of patients with Huntington's disease-like 2 and pantothenate kinase-associated neurodegeneration. Because the clinical manifestations are diverse and complicated, in this review we present features of inheritance, age of onset, neuroimaging and laboratory findings, as well as the spectrum of central and peripheral neurological abnormalities and extraneuronal involvement to help distinguish the four specific syndromes.

  18. Comprehensive molecular pathology analysis of small bowel adenocarcinoma reveals novel targets with potential for clinical utility.

    Science.gov (United States)

    Alvi, Muhammad A; McArt, Darragh G; Kelly, Paul; Fuchs, Marc-Aurel; Alderdice, Matthew; McCabe, Clare M; Bingham, Victoria; McGready, Claire; Tripathi, Shailesh; Emmert-Streib, Frank; Loughrey, Maurice B; McQuaid, Stephen; Maxwell, Perry; Hamilton, Peter W; Turkington, Richard; James, Jacqueline A; Wilson, Richard H; Salto-Tellez, Manuel

    2015-08-28

    Small bowel accounts for only 0.5% of cancer cases in the US but incidence rates have been rising at 2.4% per year over the past decade. One-third of these are adenocarcinomas but little is known about their molecular pathology and no molecular markers are available for clinical use. Using a retrospective 28 patient matched normal-tumor cohort, next-generation sequencing, gene expression arrays and CpG methylation arrays were used for molecular profiling. Next-generation sequencing identified novel mutations in IDH1, CDH1, KIT, FGFR2, FLT3, NPM1, PTEN, MET, AKT1, RET, NOTCH1 and ERBB4. Array data revealed 17% of CpGs and 5% of RNA transcripts assayed to be differentially methylated and expressed respectively (p clinically exploitable markers.

  19. Oligocone trichromacy: clinical and molecular genetic investigations

    DEFF Research Database (Denmark)

    Andersen, Mette K G; Christoffersen, Nynne L B; Sander, Birgit;

    2010-01-01

    PURPOSE: To describe the phenotype and genotype of patients with a diagnosis of oligocone trichromacy (OT). METHODS: Six unrelated patients had a detailed ophthalmic examination including color vision testing, a Goldmann visual field test, fundus photography, and full-field electroretinography (ff...... of congenital nystagmus, and subjectively normal or near-normal color vision; five patients reported photophobia. Clinical examinations revealed largely normal fundi, normal Goldmann visual field results with the IV/4e target, and normal color discrimination or mild color vision deficiency. Electrophysiological...

  20. Molecular imaging in neuroendocrine tumors : Molecular uptake mechanisms and clinical results

    NARCIS (Netherlands)

    Koopmans, Klaas P.; Neels, Oliver N.; Kema, Ido P.; Elsinga, Philip H.; Links, Thera P.; de Vries, Elisabeth G. E.; Jager, Pieter L.

    2009-01-01

    Neuroendocrine tumors can originate almost everywhere in the body and consist of a great variety of subtypes. This paper focuses on molecular imaging methods using nuclear medicine techniques in neuroendocrine tumors, coupling molecular uptake mechanisms of radiotracers with clinical results. A non-

  1. Behavioral profiles of clinically referred children with intellectual giftedness.

    Science.gov (United States)

    Guénolé, Fabian; Louis, Jacqueline; Creveuil, Christian; Baleyte, Jean-Marc; Montlahuc, Claire; Fourneret, Pierre; Revol, Olivier

    2013-01-01

    It is common that intellectually gifted children--that is, children with an IQ ≥ 130--are referred to paediatric or child neuropsychiatry clinics for socio-emotional problems and/or school underachievement or maladjustment. These clinically-referred children with intellectual giftedness are thought to typically display internalizing problems (i.e., self-focused problems reflecting overcontrol of emotion and behavior), and to be more behaviorally impaired when "highly" gifted (IQ ≥ 145) or displaying developmental asynchrony (i.e., a heterogeneous developmental pattern, reflected in a significant verbal-performance discrepancy on IQ tests). We tested all these assumptions in 143 clinically-referred gifted children aged 8 to 12, using Wechsler's intelligence profile and the Child Behavior Checklist. Compared to a normative sample, gifted children displayed increased behavioral problems in the whole symptomatic range. Internalizing problems did not predominate over externalizing ones (i.e., acted-out problems, reflecting undercontrol of emotion and behavior), revealing a symptomatic nature of behavioral syndromes more severe than expected. "Highly gifted" children did not display more behavioral problems than the "low gifted." Gifted children with a significant verbal-performance discrepancy displayed more externalizing problems and mixed behavioral syndromes than gifted children without such a discrepancy. These results suggest that developmental asynchrony matters when examining emotional and behavioral problems in gifted children.

  2. Behavioral Profiles of Clinically Referred Children with Intellectual Giftedness

    Directory of Open Access Journals (Sweden)

    Fabian Guénolé

    2013-01-01

    Full Text Available It is common that intellectually gifted children—that is, children with an IQ ≥ 130—are referred to paediatric or child neuropsychiatry clinics for socio-emotional problems and/or school underachievement or maladjustment. These clinically-referred children with intellectual giftedness are thought to typically display internalizing problems (i.e., self-focused problems reflecting overcontrol of emotion and behavior, and to be more behaviorally impaired when “highly” gifted (IQ ≥ 145 or displaying developmental asynchrony (i.e., a heterogeneous developmental pattern, reflected in a significant verbal-performance discrepancy on IQ tests. We tested all these assumptions in 143 clinically-referred gifted children aged 8 to 12, using Wechsler’s intelligence profile and the Child Behavior Checklist. Compared to a normative sample, gifted children displayed increased behavioral problems in the whole symptomatic range. Internalizing problems did not predominate over externalizing ones (i.e., acted-out problems, reflecting undercontrol of emotion and behavior, revealing a symptomatic nature of behavioral syndromes more severe than expected. “Highly gifted” children did not display more behavioral problems than the “low gifted.” Gifted children with a significant verbal-performance discrepancy displayed more externalizing problems and mixed behavioral syndromes than gifted children without such a discrepancy. These results suggest that developmental asynchrony matters when examining emotional and behavioral problems in gifted children.

  3. Molecular profiling of childhood cancer: Biomarkers and novel therapies

    Directory of Open Access Journals (Sweden)

    Federica Saletta

    2014-06-01

    General significance: The increasing recognition of the heterogeneity of molecular causes of cancer favors the continued development of molecularly targeted agents, and their transfer to pediatric and adolescent populations.

  4. Whole Transcriptome Amplification for Gene Expression Profiling and Development of Molecular Archives

    Directory of Open Access Journals (Sweden)

    Scott A. Tomlins

    2006-02-01

    Full Text Available Expression profiling of clinically obtainable tumor specimens has been hindered by the need for microgram quantities of RNA. In vitro transcription (IVT-based amplifications are most commonly used to amplify small quantities of RNA for microarray analysis. However, significant drawbacks exist with IVT-based amplification, and the need for alternative amplification methods remains. Herein, we validate whole transcriptome amplification (WTA, an exponential amplification technique that produces cDNA libraries and amplified target in 3 to 4 hours from nanogram quantities of total RNA using a combination of cDNA microarrays and quantitative polymerase chain reaction (PCR. We demonstrate that WTA material can serve as a “molecular archive” because a WTA cDNA library can be faithfully amplified through multiple rounds of PCR amplification, allowing it to serve as a bankable and distributable resource. To demonstrate applicability, WTA was combined with laser capture microdissection to profile frozen prostate tissues. Unlike most IVT-based and exponential amplification techniques, WTA does not depend on the presence of a poly-A tail. Thus, we demonstrate that WTA is compatible with artificially degraded RNA and RNA isolated from formalin-fixed paraffin-embedded tissues. Taken together, WTA represents a versatile approach to profile and archive cDNA from minute tumor samples and is compatible with partially degraded RNA.

  5. Multiplexed molecular profiling of prostate cancer specimens using semiconductor quantum dot bioconjugates

    Science.gov (United States)

    Xing, Yun; Numora, Takeo; Chung, Leland; Zhau, Haiyen; Nie, Shuming

    2007-02-01

    Quantum dots (QDs) are light emitting semi-conductor nanocrystals with novel optical properties including superior photostability, narrow emission spectra with continuous excitation spectra. These properties make QDs especially suitable for multiplexed fluorescent labeling, live cell imaging, and in vivo animal imaging. The multiplexing potential has been recognized but real applications of biological/clinical significance are few. In this study, we used quantum dots to study epithelial mesenchymal transition (EMT), an important process involved in the bone metastasis of prostate cancer. Two prostate cancer cells lines with distinct molecular profiles, representing the two ends of the EMT process, were selected for this study. Four EMT-related biomarkers including E-cadherin, N-cadherin, Vimentin, and RANKL were stained with QD-antibody conjugates with elongation factor 1alpha as the internal control. Morphological information of the QD-stained cells was obtained by digital-color imaging and quantitative information obtained by spectra analysis using a spectrometer. Two types of analysis were performed: abundance of each biomarker in the same cell line relative to the internal control; and the relative abundance of these markers between the two cell lines. Our results demonstrate the feasibility of QDs for multiplexed profiling of FFPE cells/tissue of clinical significance; however, the standardization and quantification still awaits optimization.

  6. Olmsted syndrome: clinical, molecular and therapeutic aspects.

    Science.gov (United States)

    Duchatelet, Sabine; Hovnanian, Alain

    2015-03-17

    Olmsted syndrome (OS) is a rare genodermatosis classically characterized by the combination of bilateral mutilating transgredient palmoplantar keratoderma (PPK) and periorificial keratotic plaques, but which shows considerable clinical heterogeneity. The disease starts usually at birth or in early childhood. About 73 cases have been reported worldwide. OS is observed in both sexes, although male cases are more frequent. The most suggestive symptoms associate PPK with pseudoainhum and periorificial keratotic plaques. Frequently associated features include hair and nail abnormalities, leukokeratosis, corneal default and recurrent infections. Pain and itching are variable but can be severe. Most of reported OS cases are sporadic, although familial cases with different mode of inheritance were also described. Mutations in TRPV3 (Transient receptor potential vanilloid-3) gene have recently been identified as a cause of autosomal dominant (gain-of-function mutations) or recessive OS. Mutations in MBTPS2 (membrane-bound transcription factor protease, site 2) gene were identified in a recessive X-linked form. The diagnosis relies mainly on clinical features associating severe PPK and periorificial keratotic plaques, but can be challenging in patients with incomplete phenotype or atypical features. OS has to be differentiated from other severe forms of PPK including Vohwinkel, Clouston, Papillon-Lefèvre or Haim-Munk syndromes, Mal de Meleda, pachyonychia congenita, Tyrosinemia type II and acrodermatitis enteropathica. When differential diagnoses are difficult to exclude, genetic studies are essential to search for a TRPV3 or MBTPS2 mutation. However, additional genes remain to be identified. No specific and satisfactory therapy is currently available for OS. Current treatments of hyperkeratosis (mainly emollients, keratolytics, retinoids or corticosteroids), either topical or systemic, are symptomatic and offer only temporary partial relief. Specific management of pain and

  7. Clinical and Demographic Profile of Attendees at Baghdad’s Walk-in Psychiatric Clinic

    Directory of Open Access Journals (Sweden)

    Maha S. Younis

    2013-09-01

    Full Text Available Objective: Few studies have examined clinical and demographic profile of attendees of a walk-in psychiatric clinic in countries ravaged by wars. The aim of this study is to quantify the characteristics of attendees of an open walk-in psychiatric clinic in a general hospital in Baghdad and the suburb towns of Iraq in the year 2010.Methods: As part of a retrospective survey, information on specific variables (socio-demographic background, clinical characteristics and attendance rate were sought from medical records in the year 2010 (January to December.Results: Despite the shortcomings expected from a country coming out of the ravage of war, the survey included 2,979 attendees (1,864 [63%] males and 1,115 [37%] females of a walk-in psychiatric clinic who fulfilled the inclusion criteria. The profile of attendees indicated that a majority of the cohort was self-referred with a predominance of employed males, aged 19 to 49 years, residing in Baghdad City. Depression and psychosis were the most common diagnosis given.Conclusion: The observed patterns are discussed within the available literature relevant to consultation liaison psychiatry, and specific to situations in Iraq and Arab/Islamic cultural patterning.

  8. Clinical and molecular classification of cardiomyopathies

    Directory of Open Access Journals (Sweden)

    Franco Cecchi

    2012-07-01

    Full Text Available The term “cardiomyopathies” was used for the first time 55 years ago, in 1957. Since then awareness and knowledge of this important and complex group of heart muscle diseases have improved substantially. Over these past five decades a large number of definitions, nomenclature and schemes, have been advanced by experts and consensus panel, which reflect the fast and continued advance of the scientific understanding in the field. Cardiomyopathies are a heterogeneous group of inherited myocardial diseases, which represent an important cause of disability and adverse outcome. Although considered rare diseases, the overall estimated prevalence of all cardiomyopathies is at least 3% in the general population worldwide. Furthermore, their recognition is increasing due to advances in imaging techniques and greater awareness in both the public and medical community. Cardiomyopathies represent an ideal translational model of integration between basic and clinical sciences. A multidisciplinary approach is therefore essential in order to ensure their correct diagnosis and management. In the present work, we aim to provide a concise overview of the historical background, genetic and phenotypic spectrum and evolving concepts leading to the various attempts of cardiomyopathy classifications produced over the decades.

  9. Coronary artery anomalies: prevalence and clinical profile in elderly patients

    Institute of Scientific and Technical Information of China (English)

    Gianluca Rigatelli; Giorgio Rigatelli; Mario Trivellato

    2004-01-01

    Objective Although congenital heart diseases are uncommon in the elderly, coronary artery anomalies may be incidentally discovered in old age. We sought to determine the incidence and clinical features of coronary artery anomalies (CAAs) in patients over 65 years of age. Patients and methods Medical records of patients undergoing coronary artery angiography in the years 1997-2002 at the Legnago General Hospital were retrospectively reviewed, The clinical profiles of all patients with CAAs and CAA subtypes were noted. Comparison between patients under and over 65 was performed. Data are given as mean standard deviation and as percentages. Results Sixtysix patients (1.21%, Female/Male 22/44, mean age 65.3 ± 10.6 years) out of the 5450 who underwent coronary angiography in the years 1997-2002 had CAAs. In mast cases (63%, 41/66 patients), the patients were over 65.CAAs were discovered incidentally in these elderly patients while undergoing coronary artery angiography for dilated cardiomyopathy, ischemic heart disease, and valvular heart disease in 75% of the cases (30/41 patients). Patients over 65 had more cardiac comorbidities and .a higher incidence of coronary atherosclerosis. Conclusions The angiographic incidence of CAAs in elderly patients is increasing as the population ages and this occurrence calls for a wider knowledge of the anatomy and pathophysiology of CAAs among geriatric cardiologists. Elderly patients seem to present with lower risk coronary anomalies (separated origin of left anterior descending coronary artery and circanfflex artery, origin of circumflex artery from the right sinus or the right coronary artery, double coronary artery)but have a higher risk profile compared to younger patients due to the frequency of cardiac comorbidities and superimposed coronary artery atherosclerosis.

  10. CLINICAL PROFILE OF ACUTE MYOCARDIAL INFARCTION YOUNG ADULTS

    Directory of Open Access Journals (Sweden)

    Patel G. N

    2015-08-01

    Full Text Available BACKGROUND : Although acute myocardial infarction was believed to be an uncommon entity in the young, of late there has been a rising incidence in this group of population. The analysis of its clinical profile, including the etiologic and the risk factors gains much importance, for the preventive purpose. AIMS AND OBJECTIVES: To study the clinical profile of acute MI, including the evaluation of the cardiac enzyme markers, the risk factors, the management and the complications and outcome of this g roup of patients aged 40 years or younger. RESULTS: Majority of patients belonged to the age group of 36 - 40years. 31 patients were overweight and 16 patients were obese. 46 patients (67.64% had anterior wall myocardial infarction, 22 patients had inferior wall myocardial infarction (32.35% and ST - elevation myocardial infarction was found in 69.2% of patients. Smoking/tobacco use was the most common risk factor (64.70% followed by dyslipidemia (60.29%, metabolic syndrome (52.94% diabetes mellitus (52.94 %, hyperhomocysteinemia (52.94%, alcohol consumption (48.52%, hypertension (34%, family history (26.47%, obesity (23.52%. Other than these, two patients had chronic kidney disease stage 3, two female patients were irregular oral contraceptive pill us ers, one was diagnosed as systemic lupus erythematosus and another patient had antiphospholipid antibody syndrome. Conclusions: Apart from early diagnosis and adequate treatment of acute MI in young patients, it is also essential to identify and prevent or control the risk factors at primary and secondary level.

  11. Next-generation biobanking of metastases to enable multidimensional molecular profiling in personalized medicine.

    Science.gov (United States)

    Diaz, Zuanel; Aguilar-Mahecha, Adriana; Paquet, Eric R; Basik, Mark; Orain, Michèle; Camlioglu, Errol; Constantin, André; Benlimame, Naciba; Bachvarov, Dimcho; Jannot, Guillaume; Simard, Martin J; Chabot, Benoit; Gologan, Adrian; Klinck, Roscoe; Gagnon-Kugler, Thérèse; Lespérance, Bernard; Samson, Benoit; Kavan, Petr; Alcindor, Thierry; Dalfen, Richard; Lan, Cathy; Chabot, Catherine; Buchanan, Marguerite; Przybytkowski, Ewa; Qureshi, Samia; Rousseau, Caroline; Spatz, Alan; Têtu, Bernard; Batist, Gerald

    2013-11-01

    Great advances in analytical technology coupled with accelerated new drug development and growing understanding of biological challenges, such as tumor heterogeneity, have required a change in the focus for biobanking. Most current banks contain samples of primary tumors, but linking molecular signatures to therapeutic questions requires serial biopsies in the setting of metastatic disease, next-generation of biobanking. Furthermore, an integration of multidimensional analysis of various molecular components, that is, RNA, DNA, methylome, microRNAome and post-translational modifications of the proteome, is necessary for a comprehensive view of a tumor's biology. While data using such biopsies are now regularly presented, the preanalytical variables in tissue procurement and processing in multicenter studies are seldom detailed and therefore are difficult to duplicate or standardize across sites and across studies. In the context of a biopsy-driven clinical trial, we generated a detailed protocol that includes morphological evaluation and isolation of high-quality nucleic acids from small needle core biopsies obtained from liver metastases. The protocol supports stable shipping of samples to a central laboratory, where biopsies are subsequently embedded in support media. Designated pathologists must evaluate all biopsies for tumor content and macrodissection can be performed if necessary to meet our criteria of >60% neoplastic cells and biopsy-driven study of therapeutic resistance in metastatic colorectal cancer. To ensure that our protocol was compatible with multiplex discovery platforms and that no component of the processing interfered with downstream enzymatic reactions, we performed array comparative genomic hybridization, methylation profiling, microRNA profiling, splicing variant analysis and gene expression profiling using genomic material isolated from liver biopsy cores. Our standard operating procedures for next-generation biobanking can be applied

  12. Molecular mechanism of fluoroquinolones resistance in Mycoplasma hominis clinical isolates

    OpenAIRE

    Meng Dong-Ya; Sun Chang-Jian; Yu Jing-Bo; Ma Jun; Xue Wen-Cheng

    2014-01-01

    To evaluate the molecular mechanism of fluoroquinolones resistance in Mycoplasma hominis (MH) clinical strains isolated from urogenital specimens. 15 MH clinical isolates with different phenotypes of resistance to fluoroquinolones antibiotics were screened for mutations in the quinolone resistance-determining regions (QRDRs) of DNA gyrase (gyrA and gyrB) and topoisomerase IV (parC and parE) in comparison with the reference strain PG21, which is susceptible to fluoroquinolones antibiotics. 15 ...

  13. Clinical and molecular phenotype of Aicardi-Goutieres syndrome

    OpenAIRE

    Rice, Gillian; Patrick, Teresa; Parmar, Rekha; Taylor, Claire F.; Aeby, Alec; Aicardi, Jean; Artuch, Rafael; Montalto, Simon Attard; Bacino, Carlos A.; Barroso, Bruno; Baxter, Peter; Benko, Willam S; Bergmann, Carsten; Bertini, Enrico; Biancheri, Roberta

    2007-01-01

    Aicardi-Goutieres syndrome (AGS) is a genetic encephalopathy whose clinical features mimic those of acquired in utero viral infection. AGS exhibits locus heterogeneity, with mutations identified in genes encoding the 3'-->5' exonuclease TREX1 and the three subunits of the RNASEH2 endonuclease complex. To define the molecular spectrum of AGS, we performed mutation screening in patients, from 127 pedigrees, with a clinical diagnosis of the disease. Biallelic mutations in TREX1, RNASEH2A, RNA...

  14. Multigene mutational profiling of cholangiocarcinomas identifies actionable molecular subgroups

    Science.gov (United States)

    Mafficini, Andrea; Wood, Laura D.; Corbo, Vincenzo; Melisi, Davide; Malleo, Giuseppe; Vicentini, Caterina; Malpeli, Giorgio; Antonello, Davide; Sperandio, Nicola; Capelli, Paola; Tomezzoli, Anna; Iacono, Calogero; Lawlor, Rita T.; Bassi, Claudio; Hruban, Ralph H.; Guglielmi, Alfredo; Tortora, Giampaolo; de Braud, Filippo; Scarpa, Aldo

    2014-01-01

    One-hundred-fifty-three biliary cancers, including 70 intrahepatic cholangiocarcinomas (ICC), 57 extrahepatic cholangiocarcinomas (ECC) and 26 gallbladder carcinomas (GBC) were assessed for mutations in 56 genes using multigene next-generation sequencing. Expression of EGFR and mTOR pathway genes was investigated by immunohistochemistry. At least one mutated gene was observed in 118/153 (77%) cancers. The genes most frequently involved were KRAS (28%), TP53 (18%), ARID1A (12%), IDH1/2 (9%), PBRM1 (9%), BAP1 (7%), and PIK3CA (7%). IDH1/2 (p=0.0005) and BAP1 (p=0.0097) mutations were characteristic of ICC, while KRAS (p=0.0019) and TP53 (p=0.0019) were more frequent in ECC and GBC. Multivariate analysis identified tumour stage and TP53 mutations as independent predictors of survival. Alterations in chromatin remodeling genes (ARID1A, BAP1, PBRM1, SMARCB1) were seen in 31% of cases. Potentially actionable mutations were seen in 104/153 (68%) cancers: i) KRAS/NRAS/BRAF mutations were found in 34% of cancers; ii) mTOR pathway activation was documented by immunohistochemistry in 51% of cases and by mutations in mTOR pathway genes in 19% of cancers; iii) TGF-ß/Smad signaling was altered in 10.5% cancers; iv) mutations in tyrosine kinase receptors were found in 9% cases. Our study identified molecular subgroups of cholangiocarcinomas that can be explored for specific drug targeting in clinical trials. PMID:24867389

  15. Clinical profiles associated with influenza disease in the ferret model.

    Directory of Open Access Journals (Sweden)

    Gregory V Stark

    Full Text Available Influenza A viruses continue to pose a threat to human health; thus, various vaccines and prophylaxis continue to be developed. Testing of these products requires various animal models including mice, guinea pigs, and ferrets. However, because ferrets are naturally susceptible to infection with human influenza viruses and because the disease state resembles that of human influenza, these animals have been widely used as a model to study influenza virus pathogenesis. In this report, a statistical analysis was performed to evaluate data involving 269 ferrets infected with seasonal influenza, swine influenza, and highly pathogenic avian influenza (HPAI from 16 different studies over a five year period. The aim of the analyses was to better qualify the ferret model by identifying relationships among important animal model parameters (endpoints and variables of interest, which include survival, time-to-death, changes in body temperature and weight, and nasal wash samples containing virus, in addition to significant changes from baseline in selected hematology and clinical chemistry parameters. The results demonstrate that a disease clinical profile, consisting of various changes in the biological parameters tested, is associated with various influenza A infections in ferrets. Additionally, the analysis yielded correlates of protection associated with HPAI disease in ferrets. In all, the results from this study further validate the use of the ferret as a model to study influenza A pathology and to evaluate product efficacy.

  16. Comprehensive expression profiling of tumor cell lines identifies molecular signatures of melanoma progression.

    Directory of Open Access Journals (Sweden)

    Byungwoo Ryu

    Full Text Available BACKGROUND: Gene expression profiling has revolutionized our ability to molecularly classify primary human tumors and significantly enhanced the development of novel tumor markers and therapies; however, progress in the diagnosis and treatment of melanoma over the past 3 decades has been limited, and there is currently no approved therapy that significantly extends lifespan in patients with advanced disease. Profiling studies of melanoma to date have been inconsistent due to the heterogeneous nature of this malignancy and the limited availability of informative tissue specimens from early stages of disease. METHODOLOGY/PRINCIPLE FINDINGS: In order to gain an improved understanding of the molecular basis of melanoma progression, we have compared gene expression profiles from a series of melanoma cell lines representing discrete stages of malignant progression that recapitulate critical characteristics of the primary lesions from which they were derived. Here we describe the unsupervised hierarchical clustering of profiling data from melanoma cell lines and melanocytes. This clustering identifies two distinctive molecular subclasses of melanoma segregating aggressive metastatic tumor cell lines from less-aggressive primary tumor cell lines. Further analysis of expression signatures associated with melanoma progression using functional annotations categorized these transcripts into three classes of genes: 1 Upregulation of activators of cell cycle progression, DNA replication and repair (CDCA2, NCAPH, NCAPG, NCAPG2, PBK, NUSAP1, BIRC5, ESCO2, HELLS, MELK, GINS1, GINS4, RAD54L, TYMS, and DHFR, 2 Loss of genes associated with cellular adhesion and melanocyte differentiation (CDH3, CDH1, c-KIT, PAX3, CITED1/MSG-1, TYR, MELANA, MC1R, and OCA2, 3 Upregulation of genes associated with resistance to apoptosis (BIRC5/survivin. While these broad classes of transcripts have previously been implicated in the progression of melanoma and other malignancies, the

  17. Associations of Streptococcus suis serotype 2 ribotype profiles with clinical disease and antimicrobial resistance

    DEFF Research Database (Denmark)

    Rasmussen, S. R.; Aarestrup, Frank Møller; Jensen, N. E.;

    1999-01-01

    A total of 122 Streptococcus suis serotype 2 strains were characterized thoroughly by comparing clinical and pathological observations, ribotype profiles, and antimicrobial resistance. Twenty-one different ribotype profiles were found and compared by cluster analysis, resulting in the identificat......A total of 122 Streptococcus suis serotype 2 strains were characterized thoroughly by comparing clinical and pathological observations, ribotype profiles, and antimicrobial resistance. Twenty-one different ribotype profiles were found and compared by cluster analysis, resulting in the...

  18. [Hereditary optic neuropathies: clinical and molecular genetic characteristics].

    Science.gov (United States)

    Khanakova, N A; Sheremet, N L; Loginova, A N; Chukhrova, A L; Poliakov, A V

    2013-01-01

    The article presents a review of literature on hereditary optic neuropathies: Leber mitochondrial hereditary optic neuropathy, autosomal dominant and autosomal recessive optic neuropathies, X-linked optic atrophy. Clinical and molecular genetic characteristics are covered. Isolated optic neuropathies, as well as hereditary optic disorders, being a part of a complex syndromic disease are described.

  19. Investigation of Compton profiles of molecular methane and ethane

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Xiao-Li; Xu, Long-Quan; Kang, Xu; Liu, Ya-Wei; Ni, Dong-Dong; Zhu, Lin-Fan, E-mail: lfzhu@ustc.edu.cn [Hefei National Laboratory for Physical Sciences at Microscale and Department of Modern Physics,University of Science and Technology of China, Hefei, Anhui 230026 (China); Synergetic Innovation Center of Quantum Information and Quantum Physics, University of Science and Technology of China, Hefei, Anhui 230026 (China); Yang, Ke, E-mail: yangke@sinap.ac.cn; Ma, Yong-Peng; Yan, Shuai [Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201204 (China)

    2015-02-28

    The Compton profiles of methane and ethane molecules have been determined at an incident photon energy of 20 keV based on the third generation synchrotron radiation, and the statistical accuracy of 0.2% is achieved near p{sub z} = 0. The density functional theory with aug-cc-pVTZ basis set was used to calculate the Compton profiles of methane and ethane. The present experimental Compton profiles are in better agreement with the theoretical calculations in the whole p{sub z} region than the previous experimental results, which indicates that the present experimental Compton profiles are accurate enough to serve as the benchmark data for methane and ethane molecules.

  20. Transcriptional profiling at whole population and single cell levels reveals somatosensory neuron molecular diversity

    OpenAIRE

    Chiu, Isaac M; Barrett, Lee B.; Williams, Erika K.; Strochlic, David E; Lee, Seungkyu; Weyer, Andy D.; Lou, Shan; Bryman, Gregory S; Roberson, David P.; Ghasemlou, Nader; Piccoli, Cara; Ahat, Ezgi; Wang, Victor; Cobos del Moral, Enrique Jos??; Cheryl L. Stucky

    2014-01-01

    The somatosensory nervous system is critical for the organism's ability to respond to mechanical, thermal, and nociceptive stimuli. Somatosensory neurons are functionally and anatomically diverse but their molecular profiles are not well-defined. Here, we used transcriptional profiling to analyze the detailed molecular signatures of dorsal root ganglion (DRG) sensory neurons. We used two mouse reporter lines and surface IB4 labeling to purify three major non-overlapping classes of neurons: 1)...

  1. Analysis of Stable Low-Molecular-Weight RNA Profiles of Members of the Family Rhizobiaceae

    OpenAIRE

    Velázquez, Encarna; Cruz-Sánchez, José María; Mateos, Pedro F.; Martínez-Molina, Eustoquio

    1998-01-01

    Staircase electrophoresis in polyacrylamide gels was used to analyze the stable low-molecular-weight (LMW) RNA profiles of 24 type strains belonging to the family Rhizobiaceae. This new electrophoretic technique results in good separation of the molecules forming the LMW RNA profiles. Differences in the number and distribution of the RNA bands in these profiles allowed us to identify differences among the 24 strains assayed. Species assignments based on LMW RNAs proved to be consistent with t...

  2. A New Maximum Likelihood Approach for Free Energy Profile Construction from Molecular Simulations

    OpenAIRE

    Lee, Tai-Sung; Radak, Brian K.; Pabis, Anna; York, Darrin M.

    2012-01-01

    A novel variational method for construction of free energy profiles from molecular simulation data is presented. The variational free energy profile (VFEP) method uses the maximum likelihood principle applied to the global free energy profile based on the entire set of simulation data (e.g from multiple biased simulations) that spans the free energy surface. The new method addresses common obstacles in two major problems usually observed in traditional methods for estimating free energy surfa...

  3. Demographic and clinical profile of patients with complicated unsafe abortion

    International Nuclear Information System (INIS)

    To describe the demographic and clinical profile of patients admitted as a result of complicated unsafe abortion. The study was carried out in the Department of Obstetrics and Gynaecology, Jinnah Hospital, Lahore from August 2001 to July 2002. Patients admitted with complicated unsafe abortion were evaluated regarding age, parity, marital and educational status, indication for abortion, method used, qualification of abortion providers, contraceptive usage, complications and death rate in abortion seekers. Descriptive statistics was used for describing variables. Fiftynine patients were admitted with complicated unsafe abortion. The mean age was 29 years, 95% were married and multiparous, 40% had secondary and higher education, 85% approached unqualified abortion providers who used instrumentation in more than 40% of cases for termination of pregnancy resulting in visceral trauma. More than 50% were using contraception and 5% died due to postabortion complications. Unsafe abortion is a major health problem. The associated morbidity is much higher than mortality. This study focus on the need of postabortion care and easy accessibility to contraception to improve quality of health. (author)

  4. Clinical profile of forefoot eczema: A study of 42 cases

    Directory of Open Access Journals (Sweden)

    Brar Kamal

    2005-01-01

    Full Text Available BACKGROUND : Forefoot eczema (FE is characterized by dry fissured dermatitis of the plantar surface of the feet. AIM : To study the clinical profile of FE and the possible etiological factors. METHODS : Forty-two patients with FE were included in the study. A detailed history was recorded and examination done. Fungal scrapings and patch test with Indian Standard Series (ISS were performed in all patients. RESULTS : The most common site affected was the plantar surface of the great toe in 16 (38.09% patients. Hand involvement, with fissuring and soreness of the fingertips and palm, was seen in four patients (9.5%. Seven patients (16.6% had a personal history of atopy whereas family history of atopy was present in six (14.2%. Seven patients (16.6% reported aggravation of itching with plastic, rubber or leather footwear, and 13 (30.9%, with detergents and prolonged contact with water. Negative fungal scrapings in all patients ruled out a dermatophyte infection. Patch testing with ISS was performed in 19 patients and was positive in five. CONCLUSIONS : FE is a distinctive dermatosis of the second and third decade, predominantly in females, with a multifactorial etiology, possible factors being chronic irritation, atopy, footwear and seasonal influence.

  5. PELVIC FLOOR DYSFUNCTIONS: CLINICAL AND SOCIODEMOGRAPHIC PROFILE OF UROGYNECOLOGIC OUTPATIENTS

    Directory of Open Access Journals (Sweden)

    Cássia Fernandes Coelho

    2013-01-01

    Full Text Available This study aimed to assess the socio-demographic and clinical profile of urogynecologic outpatients of a public tertiary hospital in Fortaleza, Ceará. This is a cross-sectional study whose sample consisted of 85 women with pelvic floor dysfunction. The age ranged from 27 to 86 years old (mean: 53.8±14.2. Most patients were married (54.9%, weren’t working formally (40.0% and didn’t smoke (82.4%. Approximately half was in postmenopausal period (48.2%. Most of them were multiparous (89.4% by vaginal delivery (92.9%. The main complaint reported was urinary incontinence (74.1%, and mixed urinary incontinence (MUI was the most frequent (60.0%. Over half of the patients also had pelvic organ prolapse (75.3%, and the most common defect was from the anterior vaginal wall (55.3%. The majority (57.6% had some form of anorectal dysfunction: constipation (40%, tenesmus (37.6%, fecal incontinence (16.5%. Most of the patients lost urine several times a day (57.3%, with impact on quality of life. The risk factors found are in agreement with literature data, as well as the prevalence of MUI. Given the concomitant disorders, it’s important to address all pathologies, because they are prevalent conditions with medical, social, psychological and economic implications.

  6. Time-course profiling of molecular stress responses to silver nanoparticles in the earthworm Eisenia fetida

    DEFF Research Database (Denmark)

    Hayashi, Yuya; Heckmann, Lars-Henrik; Simonsen, Vibeke;

    2013-01-01

    The molecular mechanism of silver nanoparticle (AgNP) toxicity, particularly its temporal aspect, is currently limited in the literature. This study seeks to identify and profile changes in molecular response patterns over time during soil exposure of the earthworm Eisenia fetida to AgNPs (82±27 ...

  7. Profile of low molecular weight tinzaparin sodium for anticoagulation during hemodialysis

    Directory of Open Access Journals (Sweden)

    Al-Saran Khalid

    2010-01-01

    Full Text Available Low-molecular-weight heparin (LMWH has been suggested as providing safe, effi-cient, convenient, and possibly more cost-effective anticoagulation for hemodialysis (HD than un-fractionated heparin (UFH with a single bolus dose at the start of hemodialysis effectively pre-vents clot formation in the dialyzer and bubble trap with fewer side-effects and possible benefits on uremic dyslipidemia. In this study, we compared the safety, clinical efficacy, and cost effectiveness of Tinzaparin sodium (Innohep with unfractionated heparin (UFH in 23 chronic HD patients; their extracorporeal anticoagulant protocol-consisted of UFH was switched to Tinzaparin for a period of 6 months. Clinical clotting (grade 1-4 was evaluated by visual inspection after blood draining of the air trap every hour and the dialyzer after each session. Anticoagulation with Tinzaparin sodium re-sulted in less frequent dialyzer and air-trap clotting compared to UFH (P= 001 and 0.04 respec-tively. Over 24 weeks, we observed no alteration in the serum lipid profile of the patients. There was a statistically significant improvement in the dialysis single pool Kt/V after 6 months of Tinza-parin use (1.40 ± 0.28 for Tinzaparin versus 1.23 ± 0.28 for heparin without any modification in the hemodialysis prescription. The total cost for 24 weeks use of Tinzaparin sodium was 23% more expensive compared to that for UFH. We conclude that a single bolus of Tinzaparin sodium injec-tion at the start of the dialysis session was more effective and convenient in our patients than UFH, but at a higher total cost. Furthermore, at least on the short term, there was no observed benefit on the lipid profile.

  8. High Throughput Profiling of Molecular Shapes in Crystals

    Science.gov (United States)

    Spackman, Peter R.; Thomas, Sajesh P.; Jayatilaka, Dylan

    2016-02-01

    Molecular shape is important in both crystallisation and supramolecular assembly, yet its role is not completely understood. We present a computationally efficient scheme to describe and classify the molecular shapes in crystals. The method involves rotation invariant description of Hirshfeld surfaces in terms of of spherical harmonic functions. Hirshfeld surfaces represent the boundaries of a molecule in the crystalline environment, and are widely used to visualise and interpret crystalline interactions. The spherical harmonic description of molecular shapes are compared and classified by means of principal component analysis and cluster analysis. When applied to a series of metals, the method results in a clear classification based on their lattice type. When applied to around 300 crystal structures comprising of series of substituted benzenes, naphthalenes and phenylbenzamide it shows the capacity to classify structures based on chemical scaffolds, chemical isosterism, and conformational similarity. The computational efficiency of the method is demonstrated with an application to over 14 thousand crystal structures. High throughput screening of molecular shapes and interaction surfaces in the Cambridge Structural Database (CSD) using this method has direct applications in drug discovery, supramolecular chemistry and materials design.

  9. High Throughput Profiling of Molecular Shapes in Crystals.

    Science.gov (United States)

    Spackman, Peter R; Thomas, Sajesh P; Jayatilaka, Dylan

    2016-01-01

    Molecular shape is important in both crystallisation and supramolecular assembly, yet its role is not completely understood. We present a computationally efficient scheme to describe and classify the molecular shapes in crystals. The method involves rotation invariant description of Hirshfeld surfaces in terms of of spherical harmonic functions. Hirshfeld surfaces represent the boundaries of a molecule in the crystalline environment, and are widely used to visualise and interpret crystalline interactions. The spherical harmonic description of molecular shapes are compared and classified by means of principal component analysis and cluster analysis. When applied to a series of metals, the method results in a clear classification based on their lattice type. When applied to around 300 crystal structures comprising of series of substituted benzenes, naphthalenes and phenylbenzamide it shows the capacity to classify structures based on chemical scaffolds, chemical isosterism, and conformational similarity. The computational efficiency of the method is demonstrated with an application to over 14 thousand crystal structures. High throughput screening of molecular shapes and interaction surfaces in the Cambridge Structural Database (CSD) using this method has direct applications in drug discovery, supramolecular chemistry and materials design. PMID:26908351

  10. Formalin-fixed paraffin-embedded clinical tissues show spurious copy number changes in array-CGH profiles.

    Science.gov (United States)

    Mc Sherry, E A; Mc Goldrick, A; Kay, E W; Hopkins, A M; Gallagher, W M; Dervan, P A

    2007-11-01

    Formalin-fixed paraffin-embedded (FFPE) archival clinical specimens are invaluable in discovery of prognostic and therapeutic targets for diseases such as cancer. However, the suitability of FFPE-derived genetic material for array-based comparative genomic hybridization (array-CGH) studies is underexplored. In this study, genetic profiles of matched FFPE and fresh-frozen specimens were examined to investigate DNA integrity differences between these sample types and determine the impact this may have on genetic profiles. Genomic DNA was extracted from three patient-matched FFPE and fresh-frozen clinical tissue samples. T47D breast cancer control cells were also grown in culture and processed to yield a fresh T47D sample, a fresh-frozen T47D sample and a FFPE T47D sample. DNA was extracted from all the samples; array-CGH conducted and genetic profiles of matched samples were then compared. A loss of high molecular weight DNA was observed in the FFPE clinical tissues and FFPE T47D samples. A dramatic increase in absolute number of genetic alterations was observed in all FFPE tissues relative to matched fresh-frozen counterparts. In future, alternative fixation and tissue-processing procedures, and/or new DNA extraction and CGH profiling protocols, may be implemented, enabling identification of changes involved in disease progression using stored clinical specimens.

  11. Guillain-Barré syndrome: clinical profile and management

    Directory of Open Access Journals (Sweden)

    Sudulagunta, Sreenivasa Rao

    2015-09-01

    Full Text Available Introduction: Guillain-Barré syndrome (GBS is a fulminant polyradiculoneuropathy that is acute, frequently severe and autoimmune in nature. Etiology of GBS is incompletely understood, prognosis is usually good with early detection and prompt treatment. This retrospective study was done to evaluate clinical profile, epidemiological, laboratory, and electrodiagnostic features of patients with GBS and mode of management, complications and prognostic factors.Methods: Data of 1,166 patients admitted with GBS or presented to outpatient department (previous medical records with GBS between January 2003 and January 2014 were analyzed. Results: No difference in genders noted. Around 35% of patients are above 50 years of age. Poor control of diabetes with mean HbA of 8.1 ± 2.11 is found on analysis. Seasonal occurrence in GBS is prominent in winter 484 (41.50% and mechanically ventilated were 449 (38.50% patients. 48 (4.11% deaths were attributed to GBS. Neurological analysis revealed cranial nerve involvement in 407 (34.90% patients, facial palsy in 401 (34.39% and ataxia in 88 (7.54% patients. Most patients in plasma exchange group belonged to the lower socio-economic status. Mean cerebrospinal fluid (CSF protein levels was (n=962 113.8 ± 11.8 mg/dl. Conduction block determined indirectly by absent H-reflex was noted in 891 (90.64% patients. No difference in complications and outcome is found in treatment regimens of intravenous immunoglobulin (IVIG and plasma exchange.Conclusion: Seasonal occurrence predominantly in winter is noted. Peak flow test may be a predictor of assessing requirement of mechanical ventilation and prognosis. Conduction block is the major abnormality noted in electrophysiological studies and proximal nerve segment assessing with Erb’s point stimulation has high predictive value. IVIG treatment is more expensive but is associated with less duration of hospital stay.

  12. Clinical profile of disseminated cryptococcal infection-a case series

    Institute of Scientific and Technical Information of China (English)

    Vishwanath Sathyanarayanan; Ragini Bekur; Abdul Razak; Joydeep Chakraborty

    2010-01-01

    Objective:To study disseminated cryptococcal infection in a tertiary care hospital in Southern India.Methods:The clinical profile of 12 disseminated cryptococcosis patients with the age group of28-52years was retrospectively analyzed.Results:7(58.3%) presented with fever 30 days whereas2(16.7%)did not have fever. All the12(100%) had headache, 2(16.7%)had altered sensorium, one(8%)seizure.5(41.7%) had diarrhea and vomiting.6(50%) had oral candidiasis, and anemia.9(75%)had elevated erythrocyte sedimentation rate (ESR). 6(50%) had neck stiffness. Cerebrospinal fluid (CSF) pressure was elevated in all12(100%) patients. Blood culture positive for Cryptococcus neoformans(C. neoformans) in11(91.7%) andCSF culture positive in all12 (100%), one(8%)had urine culture positive. India ink preparation was positive in 10(83.3%). CD4 count was less than50/microl in 4 (33.3%), between 50-100 in6(50%)and2(16.7%) in the range of100-200. 6(50%) were treated with parenteral amphotericin B (0.7 mg/kg/d) during intensive phase followed by oral fluconazole400 mg/d for8 weeks then maintenance oral fluconazole 200 mg/d.5(41.6%) were treated with fluconazole alone.8(66.7%) improved and4(33.3%) patients died. Among those who succumbed to the illness,2(16.7%) received amphotericin and fluconazole,2(16.7%) patients received fluconazole alone.Conclusions: Disseminated cryptococcosis can cause considerable mortality inHIV patients and immunocompromised non-HIV individuals. At times, its presentation closely mimics that of Tuberculosis. Early diagnosis and appropriate treatment should be started as early as possible.

  13. Clinical profile of patients with nascent alcohol related seizures

    Directory of Open Access Journals (Sweden)

    P Sandeep

    2013-01-01

    Full Text Available Aim: The aim of this study is to characterize the clinical profile of patients with alcohol related seizures (ARS and to identify the prevalence of idiopathic generalized epilepsy (IGE in the same. Materials and Methods: 100 consecutive male patients presenting to a tertiary care center in South India with new onset ARS were analyzed with alcohol use disorders identification test (AUDIT score. All underwent 19 channel digital scalp electroencephalography (EEG and at least computed tomography (CT scan. Results: A total of 27 patients (27% who had cortical atrophy on CT had a mean duration of alcohol intake of 23.62 years compared with 14.55 years in patients with no cortical atrophy (P < 0.001. Twenty-two patients (22% had clustering in the current episode of whom 18 had cortical atrophy. Nearly, 88% patients had generalized tonic clonic seizures while 12% who had partial seizures underwent magnetic resonance imaging (MRI, which identified frontal focal cortical dysplasia in one. Mean lifetime duration of alcohol intake in patients presenting with seizures within 6 hours (6H-gp of intake of alcohol was significantly lower (P = 0.029. One patient in the 6H-gp with no withdrawal symptoms had EEG evidence for IGE and had a lower AUDIT score compared with the rest. Conclusion: CT evidence of cortical atrophy is related to the duration of alcohol intake and portends an increased risk for clustering. Partial seizures can be a presenting feature of ARS and those patients may benefit from MRI to identify underlying symptomatic localization related epilepsy (8.3% of partial seizures. IGE is more likely in patients presenting with ARS within first 6 hours especially if they do not have alcohol withdrawal symptoms and scalp EEG is helpful to identify this small subgroup (~1% who may require long-term anti-epileptic medication.

  14. GliomaPredict: a clinically useful tool for assigning glioma patients to specific molecular subtypes

    Directory of Open Access Journals (Sweden)

    Fine Howard A

    2010-07-01

    Full Text Available Abstract Background Advances in generating genome-wide gene expression data have accelerated the development of molecular-based tumor classification systems. Tools that allow the translation of such molecular classification schemas from research into clinical applications are still missing in the emerging era of personalized medicine. Results We developed GliomaPredict as a computational tool that allows the fast and reliable classification of glioma patients into one of six previously published stratified subtypes based on sets of extensively validated classifiers derived from hundreds of glioma transcriptomic profiles. Our tool utilizes a principle component analysis (PCA-based approach to generate a visual representation of the analyses, quantifies the confidence of the underlying subtype assessment and presents results as a printable PDF file. GliomaPredict tool is implemented as a plugin application for the widely-used GenePattern framework. Conclusions GliomaPredict provides a user-friendly, clinically applicable novel platform for instantly assigning gene expression-based subtype in patients with gliomas thereby aiding in clinical trial design and therapeutic decision-making. Implemented as a user-friendly diagnostic tool, we expect that in time GliomaPredict, and tools like it, will become routinely used in translational/clinical research and in the clinical care of patients with gliomas.

  15. Molecular profiling of indolent human prostate cancer:tackling technical challenges to achieve high-fidelity genome-wide data

    Institute of Scientific and Technical Information of China (English)

    Thomas A. Dunn; Helen L. Fedor; Angelo M. De Marzo; Jun Luo

    2012-01-01

    The contemporary problem of prostate cancer overtreatment can be partially attributed to the diagnosis of potentially indolent prostate cancers that pose low risk to aged men,and lack of sufficiently accurate risk stratification methods to reliably seek out men with indolent diseases.Since progressive acquisition and accumulation of genomic alterations,both genetic and epigenetic,is a defining feature of all human cancers at different stages of disease progression,it is hypothesized that RNA and DNA alterations characteristic of indolent prostate tumors may be different from those previously characterized in the setting of clinically significant prostate cancer.Approaches capable of detecting such alterations on a genome-wide level are the most promising.Such analysis may uncover molecular events defining early initiating stages along the natural history of prostate cancer progression,and ultimately lead to rational development of risk stratification methods for identification of men who can safely forego treatment.However,defining and characterizing indolent prostate cancer in a clinically relevant context remains a challenge,particularly when genome-wide approaches are employed to profile formalin-fixed paraffin-embedded (FFPE) tissue specimens.Here,we provide the conceptual basis underlying the importance of understanding indolent prostate cancer from molecular profiling studies,identify the key hurdles in sample acquisition and variables that affect molecular data derived from FFPE tissues,and highlight recent progresses in efforts to address these technical challenges.

  16. Molecular Profiling of Activated Neurons by Phosphorylated Ribosome Capture

    OpenAIRE

    Knight, Zachary A.; Tan, Keith; Birsoy, Kivanc; Schmidt, Sarah; Garrison, Jennifer L.; Wysocki, Robert W.; Emiliano, Ana; Ekstrand, Mats I.; Friedman, Jeffrey M.

    2012-01-01

    The mammalian brain is composed of thousands of interacting neural cell types. Systematic approaches to establish the molecular identity of functional populations of neurons would advance our understanding of neural mechanisms controlling behavior. Here, we show that ribosomal protein S6, a structural component of the ribosome, becomes phosphorylated in neurons activated by a wide range of stimuli. We show that these phosphorylated ribosomes can be captured from mouse brain homogenates, there...

  17. Molecular and clinical study of 61 Angelman syndrome patients

    Energy Technology Data Exchange (ETDEWEB)

    Saitoh, Shinji; Harada, Naoki; Jinno, Yoshihiro; Niikawa, Norio [Nagasaki Univ. School of Medicine (Japan); Imaizumi, Kiyoshi; Kuroki, Yoshikazu; Fukushima; Yoshimitsu; Sugimoto, Tateo; Renedo, Monica

    1994-08-15

    We analyzed 61 Angelman syndrome (AS) patients by cytogenetic and molecular techniques. On the basis of molecular findings, the patients were classified into the following 4 groups: familial cases without deletion, familial cases with submicroscopic deletion, sporadic cases with deletion, and sporadic cases without deletion. Among 53 sporadic cases, 37 (70%) had molecular deletion, which commonly extended from D15S9 to D15S12, although not all deletions were identical. Of 8 familial cases, 3 sibs from one family had a molecular deletion involving only 2 loci, D15S10 and GABRB3, which define the critical region for AS phenotypes. The parental origin of deletion, both in sporadic and familial cases, was exclusively maternal and consistent with a genomic imprinting hypothesis. Among sporadic and familial cases without deletion, no uniparental disomy was found and most of them were shown to inherit chromosomes 15 from both parents (biparental inheritance). A discrepancy between cytogenetic and molecular deletion was observed in 14 (26%) of 53 patients in whom cytogenetic analysis could be performed. Ten (43%) of 23 patients with a normal karyotype showed a molecular deletion, and 4 (13%) of 30 patients with cytogenetic deletion, del(15) (q11q13), showed no molecular deletion. Most clinical manifestations, including neurological signs and facial characteristics, were not distinct in each group except for hypopigmentation of skin or hair. Familial cases with submicroscopic deletion were not associated with hypopigmentation. These findings suggested that a gene for hypopigmentation is located outside the critical region of AS and is not imprinted. 37 refs., 2 figs., 4 tabs.

  18. Clinical profile and outcome of posterior reversible encephalopathy syndrome (PRES

    Directory of Open Access Journals (Sweden)

    Virendra C Patil

    2015-01-01

    Full Text Available Background: Posterior reversible encephalopathy syndrome (PRES is a clinico-radiographic syndrome of multiple etiologies. Still, the exact pathophysiology of PRES is not clear. Aims and Objectives: To study demographic, etiological, and clinic-radiological profiles of patients presenting with PRES and their outcome at the tertiary care teaching hospital. Materials and Methods: A retrospective observational and non-interventional study was conducted at tertiary care center in from January 2009 to December 2013 at Krishna Institute of Medical Sciences, Karad. Inclusion Criteria: The clinical history of acute neurologic change including headache, encephalopathy, seizure, visual disturbance, or focal deficit with magnetic resonance imaging (MRI brain imaging findings of focal vasogenic edema with clinical or radiologic proof of reversibility. Results: Of a total 43 patients with suspected diagnosis of PRES, 29 patients were included fulfilling all inclusion criteria of PRES. Of total the 29 patients with confirmed diagnosis of PRES, 22 (75.86% were female and 7 (24.13% were male patients, predominated by female population (relative risk [RR]: 3.14; odds ration [OR]: 9.87; ′P′ < 0.001. The overall mean age was 33.65 years (±15.26 and mean duration of stay was 10.13 days (±4.98. The most common clinical presentation was generalized tonic-clonic seizures, seen in 23 (79.31% patients, headache in 21 (72.41% patients, and visual disturbances 13 (44.82% patients. A total of 18 (62.06% patients were hypertensive and 11 (37.93% were normotensive [RR: 1.63]. A total of 6 (27.27% females and 5 (71.42% males were normotensive and total 16 (72.72% females and 2 (28.57% males were hypertensive (RR: 1.12. Of a total of 22 female patients with PRES, 19 (86.36% were in a postpartum state, one (4.45% had systemic lupus erythematous (SLE, one (4.54% had community-acquired pneumonia (CAP with acute respiratory distress syndrome (ARDS with septicemia and one (4

  19. Molecular depth profiling of organic photovoltaic heterojunction layers by ToF-SIMS: comparative evaluation of three sputtering beams

    NARCIS (Netherlands)

    Mouhib, T.; Poleunis, C.; Wehbe, N.; Michels, J.J.; Galagan, Y.; Houssiau, L.; Bertrand, P.; Delcorte, A.

    2013-01-01

    With the recent developments in secondary ion mass spectrometry (SIMS), it is now possible to obtain molecular depth profiles and 3D molecular images of organic thin films, i.e. SIMS depth profiles where the molecular information of the mass spectrum is retained through the sputtering of the sample.

  20. Molecular risk assessment of BIG 1-98 participants by expression profiling using RNA from archival tissue

    OpenAIRE

    Giobbie-Hurder Anita; Thürlimann Beat; Oberli Andrea; Baltzer Anna; Wirapati Pratyaksha; Delorenzi Mauro; Popovici Vlad; Antonov Janine; Viale Giuseppe; Altermatt Hans; Aebi Stefan; Jaggi Rolf

    2010-01-01

    Abstract Background The purpose of the work reported here is to test reliable molecular profiles using routinely processed formalin-fixed paraffin-embedded (FFPE) tissues from participants of the clinical trial BIG 1-98 with a median follow-up of 60 months. Methods RNA from fresh frozen (FF) and FFPE tumor samples of 82 patients were used for quality control, and independent FFPE tissues of 342 postmenopausal participants of BIG 1-98 with ER-positive cancer were analyzed by measuring prospect...

  1. Resveratrol and calcium signaling: molecular mechanisms and clinical relevance.

    Science.gov (United States)

    McCalley, Audrey E; Kaja, Simon; Payne, Andrew J; Koulen, Peter

    2014-06-05

    Resveratrol is a naturally occurring compound contributing to cellular defense mechanisms in plants. Its use as a nutritional component and/or supplement in a number of diseases, disorders, and syndromes such as chronic diseases of the central nervous system, cancer, inflammatory diseases, diabetes, and cardiovascular diseases has prompted great interest in the underlying molecular mechanisms of action. The present review focuses on resveratrol, specifically its isomer trans-resveratrol, and its effects on intracellular calcium signaling mechanisms. As resveratrol's mechanisms of action are likely pleiotropic, its effects and interactions with key signaling proteins controlling cellular calcium homeostasis are reviewed and discussed. The clinical relevance of resveratrol's actions on excitable cells, transformed or cancer cells, immune cells and retinal pigment epithelial cells are contrasted with a review of the molecular mechanisms affecting calcium signaling proteins on the plasma membrane, cytoplasm, endoplasmic reticulum, and mitochondria. The present review emphasizes the correlation between molecular mechanisms of action that have recently been identified for resveratrol and their clinical implications.

  2. Resveratrol and Calcium Signaling: Molecular Mechanisms and Clinical Relevance

    Directory of Open Access Journals (Sweden)

    Audrey E. McCalley

    2014-06-01

    Full Text Available Resveratrol is a naturally occurring compound contributing to cellular defense mechanisms in plants. Its use as a nutritional component and/or supplement in a number of diseases, disorders, and syndromes such as chronic diseases of the central nervous system, cancer, inflammatory diseases, diabetes, and cardiovascular diseases has prompted great interest in the underlying molecular mechanisms of action. The present review focuses on resveratrol, specifically its isomer trans-resveratrol, and its effects on intracellular calcium signaling mechanisms. As resveratrol’s mechanisms of action are likely pleiotropic, its effects and interactions with key signaling proteins controlling cellular calcium homeostasis are reviewed and discussed. The clinical relevance of resveratrol’s actions on excitable cells, transformed or cancer cells, immune cells and retinal pigment epithelial cells are contrasted with a review of the molecular mechanisms affecting calcium signaling proteins on the plasma membrane, cytoplasm, endoplasmic reticulum, and mitochondria. The present review emphasizes the correlation between molecular mechanisms of action that have recently been identified for resveratrol and their clinical implications.

  3. Molecular profiling of biliary tract cancer: a target rich disease

    Science.gov (United States)

    Jain, Apurva

    2016-01-01

    Biliary tract cancers (BTCs) are relatively uncommon orphan tumors that have an aggressive disease course and a poor clinical outcome. Surgery is the only curative treatment, but most patients present with advanced disease and therefore have a limited survival. Gemcitabine and cisplatin based chemotherapy has been the only widely accepted standard systemic therapy regimen in these patients but these tumors can be chemoresistant, further complicating their management. In recent times, there has been considerable research in the genetics of BTC and with the advent of new, advanced technologies like next-generation sequencing (NGS) we are achieving a greater understanding of its disease biology. With the help of NGS, we have now been able to identify actionable mutations such as in the isocitrate dehydrogenase 1 (IDH1), FGFR2, BRAF and HER2/neu genes for targeted therapeutics and correlate the genetic variations with distinct clinical prognoses. This recent genetic information has the potential to make precision medicine a part of routine clinical practice for the management of BTC patients. PMID:27747093

  4. Molecular profiling of ADAM12 in human bladder cancer

    DEFF Research Database (Denmark)

    Albrechtsen, Reidar; Dyrskjøt, Lars; Rudkjaer, Lise;

    2006-01-01

    PURPOSE: We have previously found ADAM12, a disintegrin and metalloprotease, to be an interesting biomarker for breast cancer. The purpose of this study was to determine the gene and protein expression profiles of ADAM12 in different grades and stages of bladder cancer. EXPERIMENTAL DESIGN: ADAM12...... staining on tissue arrays of bladder cancers. The presence and relative amount of ADAM12 in the urine of cancer patients were determined by Western blotting and densitometric measurements, respectively. RESULTS: ADAM12 mRNA expression was significantly up-regulated in bladder cancer, as determined...... by microarray analysis, and the level of ADAM12 mRNA correlated with disease stage. Reverse transcription-PCR, quantitative PCR, and in situ hybridization validated the gene expression results. Using immunohistochemistry, we found ADAM12 protein expression correlated with tumor stage and grade. Finally, ADAM12...

  5. [Basal cell carcinoma. Molecular genetics and unusual clinical features].

    Science.gov (United States)

    Reifenberger, J

    2007-05-01

    Basal cell carcinoma is the most common human cancer. Its incidence is steadily increasing. The development of basal cell carcinoma is linked to genetic factors, including the individual skin phototype, as well as the cumulative exposure to UVB. The vast majority of basal cell carcinomas are sporadic tumors, while familial cases associated with certain hereditary syndromes are less common. At the molecular level, basal cell carcinomas are characterized by aberrant activation of sonic hedgehog signaling, usually due to mutations either in the ptch or smoh genes. In addition, about half of the cases carry mutations in the tp53 tumor suppressor gene, which are often UVB-associated C-->T transition mutations. Clinically, basal cell carcinomas may show a high degree of phenotypical variability. In particular, tumors occurring in atypical locations, showing an unusual clinical appearance, or imitating other skin diseases may cause diagnostic problems. This review article summarizes the current state of the art concerning the etiology, predisposition and molecular genetics of basal cell carcinoma. In addition, examples of unusual clinical manifestations are illustrated. PMID:17440702

  6. Molecular mechanism of fluoroquinolones resistance in Mycoplasma hominis clinical isolates

    Directory of Open Access Journals (Sweden)

    Meng Dong-Ya

    2014-01-01

    Full Text Available To evaluate the molecular mechanism of fluoroquinolones resistance in Mycoplasma hominis (MH clinical strains isolated from urogenital specimens. 15 MH clinical isolates with different phenotypes of resistance to fluoroquinolones antibiotics were screened for mutations in the quinolone resistance-determining regions (QRDRs of DNA gyrase (gyrA and gyrB and topoisomerase IV (parC and parE in comparison with the reference strain PG21, which is susceptible to fluoroquinolones antibiotics. 15 MH isolates with three kinds of quinolone resistance phenotypes were obtained. Thirteen out of these quinolone-resistant isolates were found to carry nucleotide substitutions in either gyrA or parC. There were no alterations in gyrB and no mutations were found in the isolates with a phenotype of resistance to Ofloxacin (OFX, intermediate resistant to Levofloxacin (LVX and Sparfloxacin (SFX, and those susceptible to all three tested antibiotics. The molecular mechanism of fluoroquinolone resistance in clinical isolates of MH was reported in this study. The single amino acid mutation in ParC of MH may relate to the resistance to OFX and LVX and the high-level resistance to fluoroquinolones for MH is likely associated with mutations in both DNA gyrase and the ParC subunit of topoisomerase IV.

  7. Advances and applications of molecular cloning in clinical microbiology.

    Science.gov (United States)

    Sharma, Kamal; Mishra, Ajay Kumar; Mehraj, Vikram; Duraisamy, Ganesh Selvaraj

    2014-10-01

    Molecular cloning is based on isolation of a DNA sequence of interest to obtain multiple copies of it in vitro. Application of this technique has become an increasingly important tool in clinical microbiology due to its simplicity, cost effectiveness, rapidity, and reliability. This review entails the recent advances in molecular cloning and its application in the clinical microbiology in the context of polymicrobial infections, recombinant antigens, recombinant vaccines, diagnostic probes, antimicrobial peptides, and recombinant cytokines. Culture-based methods in polymicrobial infection have many limitation, which has been overcome by cloning techniques and provide gold standard technique. Recombinant antigens produced by cloning technique are now being used for screening of HIV, HCV, HBV, CMV, Treponema pallidum, and other clinical infectious agents. Recombinant vaccines for hepatitis B, cholera, influenza A, and other diseases also use recombinant antigens which have replaced the use of live vaccines and thus reduce the risk for adverse effects. Gene probes developed by gene cloning have many applications including in early diagnosis of hereditary diseases, forensic investigations, and routine diagnosis. Industrial application of this technology produces new antibiotics in the form of antimicrobial peptides and recombinant cytokines that can be used as therapeutic agents. PMID:25023463

  8. Investigating the Fundamentals of Molecular Depth Profiling Using Strong-field Photoionization of Sputtered Neutrals

    OpenAIRE

    Willingham, D.; Brenes, D. A.; Winograd, N.; Wucher, A

    2011-01-01

    Molecular depth profiles of model organic thin films were performed using a 40 keV C60+ cluster ion source in concert with TOF-SIMS. Strong-field photoionization of intact neutral molecules sputtered by 40 keV C60+ primary ions was used to analyze changes in the chemical environment of the guanine thin films as a function of ion fluence. Direct comparison of the secondary ion and neutral components of the molecular depth profiles yields valuable information about chemical damage accumulation ...

  9. MOLECULAR PROFILING AND ANTIMICROBIAL ACTIVITY OF BACTERIOCIN FROM BACILLUS SUBTILIS

    Directory of Open Access Journals (Sweden)

    Berlina Dhas S

    2012-12-01

    Full Text Available Development of multi drug resistant organism has been high due to improper use of antibiotics. That made the necessity to develop new drug molecules. In this study an effort was made to find a new alternative. A wild type microorganism was isolated from soil and was identified as Bacillus and confirmed as Bacillus subtilis species by 16S r RNA sequencing. The strain was identified to have the ability to produce bacteriocin by stab overlay assay. Bacteriocin was produced in nutrient broth and that was extracted by organic solvent extraction using chloroform and further purification was carried out by HPLC and the molecular weight of the bacteriocin was analysed by SDSPAGE. Antimicrobial activity was analysed on four strains Pseudomonas sp, Staphylococcus sp, Klebsiella sp and Proteus sp. and was found to be sensitive towards the analyzed strains.

  10. Molecular profiling of activated neurons by phosphorylated ribosome capture.

    Science.gov (United States)

    Knight, Zachary A; Tan, Keith; Birsoy, Kivanc; Schmidt, Sarah; Garrison, Jennifer L; Wysocki, Robert W; Emiliano, Ana; Ekstrand, Mats I; Friedman, Jeffrey M

    2012-11-21

    The mammalian brain is composed of thousands of interacting neural cell types. Systematic approaches to establish the molecular identity of functional populations of neurons would advance our understanding of neural mechanisms controlling behavior. Here, we show that ribosomal protein S6, a structural component of the ribosome, becomes phosphorylated in neurons activated by a wide range of stimuli. We show that these phosphorylated ribosomes can be captured from mouse brain homogenates, thereby enriching directly for the mRNAs expressed in discrete subpopulations of activated cells. We use this approach to identify neurons in the hypothalamus regulated by changes in salt balance or food availability. We show that galanin neurons are activated by fasting and that prodynorphin neurons restrain food intake during scheduled feeding. These studies identify elements of the neural circuit that controls food intake and illustrate how the activity-dependent capture of cell-type-specific transcripts can elucidate the functional organization of a complex tissue. PMID:23178128

  11. Elemental and molecular profiling of licit, illicit, and niche tobacco.

    Science.gov (United States)

    Quayle, Kim; Clemens, Graeme; Sorribes, Tamar Garcia; Kinvig, Hannah M; Stevenson, Paul G; Conlan, Xavier A; Baker, Matthew J

    2016-09-01

    The recognition of differences between regulated large-scale mass manufactured products and the uncontrolled cultivation of tobaccos for illicit purposes plays a significant role within identification of provenance. This research highlights X-ray fluorescence and Fourier transform infrared spectroscopy as useful analytical techniques for the rapid identification of tobacco samples of unknown provenance. Identification of key discriminative features within each technique allowed for the development of typical characteristic profiles for each type of tobacco. Analysis using X-ray fluorescence highlights chlorine, potassium, calcium and iron as key elemental indicators of tobacco provenance. Significant levels of chlorine seen within Snüs samples prompted attempts to visualise chlorine containing regions and structures within the sample. Scanning electron microscopy images showed crystalline structures visible within the Snüs tobacco, structures which Energy dispersive X-ray spectroscopy qualitatively confirmed to contain chlorine. Chloride levels within Snüs samples were quantified using ion chromatography with levels found to range between 0.87mgmL(-1) and 1.28mg. Additionally, FTIR indicated that absorbances attributed to carbonyl stretching at 1050-1150cm(-1), alkane bending at 1350-1480cm(-1) and amide I stretching at 1600-1700cm(-1) highlighting a spectral fingerprint region that allowed for the clear differentiation between different types of tobaccos using PCA analysis, but was limited by differentiation between provenance of cigarettes and hand rolled tobacco. X-ray fluorescence and Fourier transform infrared spectroscopy yielded different information with regards tobacco discrimination and provenance, however both methods overall analysis time and cost reduced indicating usefulness as potential handheld analytical techniques in the field. PMID:27514016

  12. Targeted Therapy Database (TTD: a model to match patient's molecular profile with current knowledge on cancer biology.

    Directory of Open Access Journals (Sweden)

    Simone Mocellin

    Full Text Available BACKGROUND: The efficacy of current anticancer treatments is far from satisfactory and many patients still die of their disease. A general agreement exists on the urgency of developing molecularly targeted therapies, although their implementation in the clinical setting is in its infancy. In fact, despite the wealth of preclinical studies addressing these issues, the difficulty of testing each targeted therapy hypothesis in the clinical arena represents an intrinsic obstacle. As a consequence, we are witnessing a paradoxical situation where most hypotheses about the molecular and cellular biology of cancer remain clinically untested and therefore do not translate into a therapeutic benefit for patients. OBJECTIVE: To present a computational method aimed to comprehensively exploit the scientific knowledge in order to foster the development of personalized cancer treatment by matching the patient's molecular profile with the available evidence on targeted therapy. METHODS: To this aim we focused on melanoma, an increasingly diagnosed malignancy for which the need for novel therapeutic approaches is paradigmatic since no effective treatment is available in the advanced setting. Relevant data were manually extracted from peer-reviewed full-text original articles describing any type of anti-melanoma targeted therapy tested in any type of experimental or clinical model. To this purpose, Medline, Embase, Cancerlit and the Cochrane databases were searched. RESULTS AND CONCLUSIONS: We created a manually annotated database (Targeted Therapy Database, TTD where the relevant data are gathered in a formal representation that can be computationally analyzed. Dedicated algorithms were set up for the identification of the prevalent therapeutic hypotheses based on the available evidence and for ranking treatments based on the molecular profile of individual patients. In this essay we describe the principles and computational algorithms of an original method

  13. CLINICAL SIGNIFICANCE OF HEMOSTATIC MOLECULAR MARKERS IN ACUTE LEUKEMIA

    Institute of Scientific and Technical Information of China (English)

    吴方; 王学锋; 璩斌; 王鸿利; 沈志祥; 王振义

    2002-01-01

    Objective To elucidate the clinical significance of hemostatic molecular markers changes in acute leukemia (AL). Methods A series of hemostatic molecular markers including tissue factor ( TF) , tissue factor pathway inhibitor (TFPI), thrombin-antithrombin complex (TAT), plasmin anti-plasmin complex (PAP), urokinase-type plasminogen activator (u-PA), and urokinase-type plasminogen activator receptor ( uPAR) were measured in AL. Results The plasma level of TF, TAT, u-PA and u-PAR was significantly elevated before treatment, while in acute myeloid leukemia ( AML ) , only the level of TFPl and PAP increased.After treatment, TF and TAT remained at high level in AML, u-PA and u-PAR were still abnormal except in patients who obtained complete remission ( CR ). PAP and u-PA elevated remarkably in patient with severe hemorrhage. Conclusion The results indicated that there was hemostatic abnormal as well as hyperfibrinolysis in AL, which varied with different type of AL and can be ameliorated with clinical improvement. The measurement of TF, TAT, PAP may provide useful information for the diagnosis of DIC ; u-PA, u-PAR may be considered as useful markers for prognosis. Patient with sever hemorrhage should be treated with antifibrinolysis drugs, and great attention should be paid to prevent hypercoagulability in patients with AML after chemotherapeutic treatment.

  14. Clinical profile of hospital acquired pneumonia in a tertiary care hospital, South India

    OpenAIRE

    Vasuki V.

    2016-01-01

    Background: Hospital acquired infections continue to be an important cause of morbidity and mortality among hospitalized patients. Hospital acquired pneumonia (HAP) results in a significant increase in the cost of care of hospitalized patients. Its development prolongs a patient's stay in the Intensive Care Unit (ICU). Accurate information concerning the clinical profile of HAP is lacking in South India. This study was conducted prospectively to evaluate the clinical profile of HAP in ICU pat...

  15. Gene expression profiles give insight into the molecular pathology of bone in primary hyperparathyroidism

    DEFF Research Database (Denmark)

    Reppe, Sjur; Stilgren, Lis; Olstad, Ole K;

    2006-01-01

    Global gene expression profiling has been used to study the molecular mechanisms of increased bone remodeling caused by PHPT. This disease is a model for chronic over-stimulation of target organs by PTH due to an inappropriate overproduction of the hormone. Hyperactivity of osteoblasts and osteoc......Global gene expression profiling has been used to study the molecular mechanisms of increased bone remodeling caused by PHPT. This disease is a model for chronic over-stimulation of target organs by PTH due to an inappropriate overproduction of the hormone. Hyperactivity of osteoblasts...... and osteoclasts lead to increased calcium and phosphate mobilization from the skeleton and hypercalcaemia. The ensemble of genes that alter expression and thus is responsible for the effects of chronic PTH stimulation is today largely unknown. The differentiated gene expression profiles revealed characteristic...

  16. Molecular classification of fatty liver by high-throughput profiling of protein post-translational modifications.

    Science.gov (United States)

    Urasaki, Yasuyo; Fiscus, Ronald R; Le, Thuc T

    2016-04-01

    We describe an alternative approach to classifying fatty liver by profiling protein post-translational modifications (PTMs) with high-throughput capillary isoelectric focusing (cIEF) immunoassays. Four strains of mice were studied, with fatty livers induced by different causes, such as ageing, genetic mutation, acute drug usage, and high-fat diet. Nutrient-sensitive PTMs of a panel of 12 liver metabolic and signalling proteins were simultaneously evaluated with cIEF immunoassays, using nanograms of total cellular protein per assay. Changes to liver protein acetylation, phosphorylation, and O-N-acetylglucosamine glycosylation were quantified and compared between normal and diseased states. Fatty liver tissues could be distinguished from one another by distinctive protein PTM profiles. Fatty liver is currently classified by morphological assessment of lipid droplets, without identifying the underlying molecular causes. In contrast, high-throughput profiling of protein PTMs has the potential to provide molecular classification of fatty liver.

  17. Absolute density-profile tomography of molecular beams using multiphoton ionization

    International Nuclear Information System (INIS)

    We describe an approach for the absolute density measurement of rotationally symmetric molecular beams via multiphoton ionization. This simple single-projection tomographic technique requires only knowledge of the spatial intensity profile and ionization characteristics of the focused laser beam that probes the pulsed molecular jet. Multiphoton ionization (MPI) of a xenon beam allowed tomographic reconstruction of a two-dimensional density profile with a peak density of (4.2±0.4)x1018 m-3, which was compared with the theoretical predictions of the sudden freeze model. An analytic solution to the Abel transform is derived for Gaussian projected density profiles which greatly simplifies the reconstruction of the absolute radial density. MPI is sufficiently general that this technique can be readily applied to atomic beams with a broad range of chemistries.

  18. Correlation of microarray-based breast cancer molecular subtypes and clinical outcomes: implications for treatment optimization

    International Nuclear Information System (INIS)

    Optimizing treatment through microarray-based molecular subtyping is a promising method to address the problem of heterogeneity in breast cancer; however, current application is restricted to prediction of distant recurrence risk. This study investigated whether breast cancer molecular subtyping according to its global intrinsic biology could be used for treatment customization. Gene expression profiling was conducted on fresh frozen breast cancer tissue collected from 327 patients in conjunction with thoroughly documented clinical data. A method of molecular subtyping based on 783 probe-sets was established and validated. Statistical analysis was performed to correlate molecular subtypes with survival outcome and adjuvant chemotherapy regimens. Heterogeneity of molecular subtypes within groups sharing the same distant recurrence risk predicted by genes of the Oncotype and MammaPrint predictors was studied. We identified six molecular subtypes of breast cancer demonstrating distinctive molecular and clinical characteristics. These six subtypes showed similarities and significant differences from the Perou-Sørlie intrinsic types. Subtype I breast cancer was in concordance with chemosensitive basal-like intrinsic type. Adjuvant chemotherapy of lower intensity with CMF yielded survival outcome similar to those of CAF in this subtype. Subtype IV breast cancer was positive for ER with a full-range expression of HER2, responding poorly to CMF; however, this subtype showed excellent survival when treated with CAF. Reduced expression of a gene associated with methotrexate sensitivity in subtype IV was the likely reason for poor response to methotrexate. All subtype V breast cancer was positive for ER and had excellent long-term survival with hormonal therapy alone following surgery and/or radiation therapy. Adjuvant chemotherapy did not provide any survival benefit in early stages of subtype V patients. Subtype V was consistent with a unique subset of luminal A intrinsic

  19. The emergence of molecular profiling and omics techniques in seagrass biology; furthering our understanding of seagrasses.

    Science.gov (United States)

    Davey, Peter A; Pernice, Mathieu; Sablok, Gaurav; Larkum, Anthony; Lee, Huey Tyng; Golicz, Agnieszka; Edwards, David; Dolferus, Rudy; Ralph, Peter

    2016-09-01

    Seagrass meadows are disappearing at alarming rates as a result of increasing coastal development and climate change. The emergence of omics and molecular profiling techniques in seagrass research is timely, providing a new opportunity to address such global issues. Whilst these applications have transformed terrestrial plant research, they have only emerged in seagrass research within the past decade; In this time frame we have observed a significant increase in the number of publications in this nascent field, and as of this year the first genome of a seagrass species has been sequenced. In this review, we focus on the development of omics and molecular profiling and the utilization of molecular markers in the field of seagrass biology. We highlight the advances, merits and pitfalls associated with such technology, and importantly we identify and address the knowledge gaps, which to this day prevent us from understanding seagrasses in a holistic manner. By utilizing the powers of omics and molecular profiling technologies in integrated strategies, we will gain a better understanding of how these unique plants function at the molecular level and how they respond to on-going disturbance and climate change events. PMID:27443314

  20. Molecular diagnosis in clinical parasitology: when and why?

    Science.gov (United States)

    Wong, Samson S Y; Fung, Kitty S C; Chau, Sandy; Poon, Rosana W S; Wong, Sally C Y; Yuen, Kwok-Yung

    2014-11-01

    Microscopic detection and morphological identification of parasites from clinical specimens are the gold standards for the laboratory diagnosis of parasitic infections. The limitations of such diagnostic assays include insufficient sensitivity and operator dependence. Immunoassays for parasitic antigens are not available for most parasitic infections and have not significantly improved the sensitivity of laboratory detection. Advances in molecular detection by nucleic acid amplification may improve the detection in asymptomatic infections with low parasitic burden. Rapidly accumulating genomic data on parasites allow the design of polymerase chain reaction (PCR) primers directed towards multi-copy gene targets, such as the ribosomal and mitochondrial genes, which further improve the sensitivity. Parasitic cell or its free circulating parasitic DNA can be shed from parasites into blood and excreta which may allow its detection without the whole parasite being present within the portion of clinical sample used for DNA extraction. Multiplex nucleic acid amplification technology allows the simultaneous detection of many parasitic species within a single clinical specimen. In addition to improved sensitivity, nucleic acid amplification with sequencing can help to differentiate different parasitic species at different stages with similar morphology, detect and speciate parasites from fixed histopathological sections and identify anti-parasitic drug resistance. The use of consensus primer and PCR sequencing may even help to identify novel parasitic species. The key limitation of molecular detection is the technological expertise and expense which are usually lacking in the field setting at highly endemic areas. However, such tests can be useful for screening important parasitic infections in asymptomatic patients, donors or recipients coming from endemic areas in the settings of transfusion service or tertiary institutions with transplantation service. Such tests can also

  1. Measurement of the density profile of pure and seeded molecular beams by femtosecond ion imaging.

    Science.gov (United States)

    Meng, Congsen; Janssen, Maurice H M

    2015-02-01

    Here, we report on femtosecond ion imaging experiments to measure the density profile of a pulsed supersonic molecular beam. Ion images are measured for both a molecular beam and bulk gas under identical experimental conditions via femtosecond multiphoton ionization of Xe atoms. We report the density profile of the molecular beam, and the measured absolute density is compared with theoretical calculations of the centre line beam density. Subsequently, we discuss reasons accounting for the differences between measurements and calculations and propose that strong skimmer interference is the most probable cause for the differences. Furthermore, we report on experiments measuring the centre line density of seeded supersonic beams. The femtosecond ion images show that seeding the heavy Xe atom at low relative seed fractions (1%-10%) in a light carrier gas like Ne results in strong relative enhancements of up to two orders of magnitude. PMID:25725826

  2. CLINICAL PROFILE OF DIABETIC FOOT ULCERS OF PATIENTS ATTENDING SURGICAL OPD IN RURAL MEDICAL COLLEGE

    Directory of Open Access Journals (Sweden)

    Sanjeev

    2015-12-01

    Full Text Available OBJECTIVE To study the clinical profile of dibetic foot ulcers of patients attending surgical OPD in rural medical college. MATERIAL AND METHODS Clinical profile of 40 patients of diabetic foot ulcers was studied. All the patients were subjected to complete haemogram, fasting and PP blood sugar, LFT, KFT, lipid profile, urine R/E, pus c/s, colour doppler of lower limb and x-ray foot. RESULTS Majority of patients with diabetic foot ulcers were of age group 41–70, male, diabetes mellitus of duration more than 6 years, had intermittent claudication and single ulcer.

  3. Molecular dynamics simulation of temperature profile in partially hydrogenated graphene and graphene with grain boundary.

    Science.gov (United States)

    Lotfi, Erfan; Neek-Amal, M; Elahi, M

    2015-11-01

    Temperature profile in graphene, graphene with grain boundary and vacancy defects and hydrogenated graphene with different percentage of H-atoms are determined using molecular dynamics simulation. We also obtained the temperature profile in a graphene nanoribbon containing two types of grain boundaries with different misorientation angles, θ=21.8° and θ=32.2°. We found that a temperature gap appears in the temperature profile of a graphene nanoribbon with a grain boundary at the middle. Moreover, we found that the temperature profile in the partially hydrogenated graphene varies with the percentage of hydrogens, i.e. the C:H ratio. Our results show that a grain boundary line in the graphene sheet can change the thermal transport through the system which might be useful for controlling thermal flow in nanostructured graphene.

  4. Profiling of the Molecular Weight and Structural Isomer Abundance of Macroalgae-Derived Phlorotannins

    Directory of Open Access Journals (Sweden)

    Natalie Heffernan

    2015-01-01

    Full Text Available Phlorotannins are a group of complex polymers of phloroglucinol (1,3,5-trihydroxybenzene unique to macroalgae. These phenolic compounds are integral structural components of the cell wall in brown algae, but also play many secondary ecological roles such as protection from UV radiation and defense against grazing. This study employed Ultra Performance Liquid Chromatography (UPLC with tandem mass spectrometry to investigate isomeric complexity and observed differences in phlorotannins derived from macroalgae harvested off the Irish coast (Fucus serratus, Fucus vesiculosus, Himanthalia elongata and Cystoseira nodicaulis. Antioxidant activity and total phenolic content assays were used as an index for producing phlorotannin fractions, enriched using molecular weight cut-off dialysis with subsequent flash chromatography to profile phlorotannin isomers in these macroalgae. These fractions were profiled using UPLC-MS with multiple reaction monitoring (MRM and the level of isomerization for specific molecular weight phlorotannins between 3 and 16 monomers were determined. The majority of the low molecular weight (LMW phlorotannins were found to have a molecular weight range equivalent to 4–12 monomers of phloroglucinol. The level of isomerization within the individual macroalgal species differed, resulting in substantially different numbers of phlorotannin isomers for particular molecular weights. F. vesiculosus had the highest number of isomers of 61 at one specific molecular mass, corresponding to 12 phloroglucinol units (PGUs. These results highlight the complex nature of these extracts and emphasize the challenges involved in structural elucidation of these compounds.

  5. Clinical and molecular phenotype of Aicardi-Goutieres syndrome.

    Science.gov (United States)

    Rice, Gillian; Patrick, Teresa; Parmar, Rekha; Taylor, Claire F; Aeby, Alec; Aicardi, Jean; Artuch, Rafael; Montalto, Simon Attard; Bacino, Carlos A; Barroso, Bruno; Baxter, Peter; Benko, Willam S; Bergmann, Carsten; Bertini, Enrico; Biancheri, Roberta; Blair, Edward M; Blau, Nenad; Bonthron, David T; Briggs, Tracy; Brueton, Louise A; Brunner, Han G; Burke, Christopher J; Carr, Ian M; Carvalho, Daniel R; Chandler, Kate E; Christen, Hans-Jurgen; Corry, Peter C; Cowan, Frances M; Cox, Helen; D'Arrigo, Stefano; Dean, John; De Laet, Corinne; De Praeter, Claudine; Dery, Catherine; Ferrie, Colin D; Flintoff, Kim; Frints, Suzanna G M; Garcia-Cazorla, Angels; Gener, Blanca; Goizet, Cyril; Goutieres, Francoise; Green, Andrew J; Guet, Agnes; Hamel, Ben C J; Hayward, Bruce E; Heiberg, Arvid; Hennekam, Raoul C; Husson, Marie; Jackson, Andrew P; Jayatunga, Rasieka; Jiang, Yong-Hui; Kant, Sarina G; Kao, Amy; King, Mary D; Kingston, Helen M; Klepper, Joerg; van der Knaap, Marjo S; Kornberg, Andrew J; Kotzot, Dieter; Kratzer, Wilfried; Lacombe, Didier; Lagae, Lieven; Landrieu, Pierre Georges; Lanzi, Giovanni; Leitch, Andrea; Lim, Ming J; Livingston, John H; Lourenco, Charles M; Lyall, E G Hermione; Lynch, Sally A; Lyons, Michael J; Marom, Daphna; McClure, John P; McWilliam, Robert; Melancon, Serge B; Mewasingh, Leena D; Moutard, Marie-Laure; Nischal, Ken K; Ostergaard, John R; Prendiville, Julie; Rasmussen, Magnhild; Rogers, R Curtis; Roland, Dominique; Rosser, Elisabeth M; Rostasy, Kevin; Roubertie, Agathe; Sanchis, Amparo; Schiffmann, Raphael; Scholl-Burgi, Sabine; Seal, Sunita; Shalev, Stavit A; Corcoles, C Sierra; Sinha, Gyan P; Soler, Doriette; Spiegel, Ronen; Stephenson, John B P; Tacke, Uta; Tan, Tiong Yang; Till, Marianne; Tolmie, John L; Tomlin, Pam; Vagnarelli, Federica; Valente, Enza Maria; Van Coster, Rudy N A; Van der Aa, Nathalie; Vanderver, Adeline; Vles, Johannes S H; Voit, Thomas; Wassmer, Evangeline; Weschke, Bernhard; Whiteford, Margo L; Willemsen, Michel A A; Zankl, Andreas; Zuberi, Sameer M; Orcesi, Simona; Fazzi, Elisa; Lebon, Pierre; Crow, Yanick J

    2007-10-01

    Aicardi-Goutieres syndrome (AGS) is a genetic encephalopathy whose clinical features mimic those of acquired in utero viral infection. AGS exhibits locus heterogeneity, with mutations identified in genes encoding the 3'-->5' exonuclease TREX1 and the three subunits of the RNASEH2 endonuclease complex. To define the molecular spectrum of AGS, we performed mutation screening in patients, from 127 pedigrees, with a clinical diagnosis of the disease. Biallelic mutations in TREX1, RNASEH2A, RNASEH2B, and RNASEH2C were observed in 31, 3, 47, and 18 families, respectively. In five families, we identified an RNASEH2A or RNASEH2B mutation on one allele only. In one child, the disease occurred because of a de novo heterozygous TREX1 mutation. In 22 families, no mutations were found. Null mutations were common in TREX1, although a specific missense mutation was observed frequently in patients from northern Europe. Almost all mutations in RNASEH2A, RNASEH2B, and RNASEH2C were missense. We identified an RNASEH2C founder mutation in 13 Pakistani families. We also collected clinical data from 123 mutation-positive patients. Two clinical presentations could be delineated: an early-onset neonatal form, highly reminiscent of congenital infection seen particularly with TREX1 mutations, and a later-onset presentation, sometimes occurring after several months of normal development and occasionally associated with remarkably preserved neurological function, most frequently due to RNASEH2B mutations. Mortality was correlated with genotype; 34.3% of patients with TREX1, RNASEH2A, and RNASEH2C mutations versus 8.0% RNASEH2B mutation-positive patients were known to have died (P=.001). Our analysis defines the phenotypic spectrum of AGS and suggests a coherent mutation-screening strategy in this heterogeneous disorder. Additionally, our data indicate that at least one further AGS-causing gene remains to be identified.

  6. Clinical and Molecular Characteristics of Post-Colonoscopy Colorectal Cancer

    DEFF Research Database (Denmark)

    Stoffel, Elena M; Erichsen, Rune; Frøslev, Trine;

    2016-01-01

    BACKGROUND AND AIMS: Colonoscopy provides incomplete protection from colorectal cancer (CRC), but determinants of post-colonoscopy CRC are not well understood. We compared clinical features and molecular characteristics of CRCs diagnosed at different time intervals after a previous colonoscopy....... METHODS: We performed a population-based, cross-sectional study of incident CRC cases in Denmark (2007-2011), categorized as post-colonoscopy or detected during diagnostic colonoscopy (in patients with no prior colonoscopy). We compared prevalence of proximal location and DNA mismatch repair deficiency (d......MMR) in CRC tumors, relative to time since previous colonoscopy, using logistic regression and cubic splines to assess temporal variation. RESULTS: Of 10,365 incident CRCs, 725 occurred after colonoscopy examinations (7.0%). These were more often located in the proximal colon (odds ratio [OR], 2.34; 95% CI, 1...

  7. Molecular identification of Sporothrix clinical isolates in China.

    Science.gov (United States)

    Liu, Ting-ting; Zhang, Ke; Zhou, Xun

    2014-01-01

    In this study, we investigated the molecular phylogeny of 64 clinical isolates which were identified as Sporothrix schenckii sensu lato by morphological identification. All of the strains were isolates from patients from several provinces in China. The phylogeny was inferred by DNA sequence analyses based on datasets of the ribosomal internal transcribed spacer (ITS) and a combined ITS and partial β-tubulin region. Reference sequences were retrieved from GenBank. Results showed that all of the isolates were clustered in a distinct clade with a type of Sporothrix globosa. Our analysis showed that S. globosa is the causal agent of the tested sporotrichosis in China, rather than S. schenckii that was generally believed to be the case. The existence of S. schenckii in China remains to be confirmed. This study improved our understanding of the distribution of the species in S. schenckii complex.

  8. Predicting Low Energy Dopant Implant Profiles in Semiconductors using Molecular Dynamics

    Energy Technology Data Exchange (ETDEWEB)

    Beardmore, K.M.; Gronbech-Jensen, N.

    1999-05-02

    The authors present a highly efficient molecular dynamics scheme for calculating dopant density profiles in group-IV alloy, and III-V zinc blende structure materials. Their scheme incorporates several necessary methods for reducing computational overhead, plus a rare event algorithm to give statistical accuracy over several orders of magnitude change in the dopant concentration. The code uses a molecular dynamics (MD) model to describe ion-target interactions. Atomic interactions are described by a combination of 'many-body' and pair specific screened Coulomb potentials. Accumulative damage is accounted for using a Kinchin-Pease type model, inelastic energy loss is represented by a Firsov expression, and electronic stopping is described by a modified Brandt-Kitagawa model which contains a single adjustable ion-target dependent parameter. Thus, the program is easily extensible beyond a given validation range, and is therefore truly predictive over a wide range of implant energies and angles. The scheme is especially suited for calculating profiles due to low energy and to situations where a predictive capability is required with the minimum of experimental validation. They give examples of using the code to calculate concentration profiles and 2D 'point response' profiles of dopants in crystalline silicon and gallium-arsenide. Here they can predict the experimental profile over five orders of magnitude for <100> and <110> channeling and for non-channeling implants at energies up to hundreds of keV.

  9. Clinical and laboratory profile of dengue in the elderly

    OpenAIRE

    Unnikrishnan, Rahul; Faizal, Baiju P.; Vijayakumar, Priya; Paul, George; Sharma, R. N.

    2015-01-01

    Background: Dengue is the most rapidly spreading mosquito-borne viral disease in the world with a 30-fold increase in incidence in the last 50 years. Approximately, 50 million dengue infections occur annually. Aim: To study the various clinical and laboratory manifestations of dengue in the elderly and observe for any variations in IgM titer elevation with progression of age. Design: Retrospective observational study. Subjects and Methods: Medical charts of all patients admitted to the Divisi...

  10. Real time and label free profiling of clinically relevant exosomes.

    Science.gov (United States)

    Sina, Abu Ali Ibn; Vaidyanathan, Ramanathan; Dey, Shuvashis; Carrascosa, Laura G; Shiddiky, Muhammad J A; Trau, Matt

    2016-01-01

    Tumor-derived exosomes possess significant clinical relevance due to their unique composition of genetic and protein material that is representative of the parent tumor. Specific isolation as well as identification of proportions of these clinically relevant exosomes (CREs) from biological samples could help to better understand their clinical significance as cancer biomarkers. Herein, we present a simple approach for quantification of the proportion of CREs within the bulk exosome population isolated from patient serum. This proportion of CREs can potentially inform on the disease stage and enable non-invasive monitoring of inter-individual variations in tumor-receptor expression levels. Our approach utilises a Surface Plasmon Resonance (SPR) platform to quantify the proportion of CREs in a two-step strategy that involves (i) initial isolation of bulk exosome population using tetraspanin biomarkers (i.e., CD9, CD63), and (ii) subsequent detection of CREs within the captured bulk exosomes using tumor-specific markers (e.g., human epidermal growth factor receptor 2 (HER2)). We demonstrate the isolation of bulk exosome population and detection of as low as 10% HER2(+) exosomes from samples containing designated proportions of HER2(+) BT474 and HER2(-) MDA-MB-231 cell derived exosomes. We also demonstrate the successful isolation of exosomes from a small cohort of breast cancer patient samples and identified that approximately 14-35% of their bulk population express HER2. PMID:27464736

  11. Gram-negative osteomyelitis: clinical and microbiological profile

    Directory of Open Access Journals (Sweden)

    Vladimir Cordeiro de Carvalho

    2012-02-01

    Full Text Available INTRODUCTION: Despite the growing interest in the study of Gram-negative bacilli (GNB infections, very little information on osteomyelitis caused by GNB is available in the medical literature. OBJECTIVES AND METHODS: To assess clinical and microbiological features of 101 cases of osteomyelitis caused by GNB alone, between January 2007 and January 2009, in a reference center for the treatment of high complexity traumas in the city of São Paulo. RESULTS: Most patients were men (63%, with median age of 42 years, affected by chronic osteomyelitis (43% or acute osteomyelitis associated to open fractures (32%, the majority on the lower limbs (71%. The patients were treated with antibiotics as inpatients for 40 days (median and for 99 days (median in outpatient settings. After 6 months follow-up, the clinical remission rate was around 60%, relapse 19%, amputation 7%, and death 5%. Nine percent of cases were lost to follow-up. A total of 121 GNB was isolated from 101 clinical samples. The most frequently isolated pathogens were Enterobacter sp. (25%, Acinetobacter baumannii (21% e Pseudomonas aeruginosa (20%. Susceptibility to carbapenems was about 100% for Enterobacter sp., 75% for Pseudomonas aeruginosa and 60% for Acinetobacter baumannii. CONCLUSION: Osteomyelitis caused by GNB remains a serious therapeutic challenge, especially when associated to nonfermenting bacteria. We emphasize the need to consider these agents in diagnosed cases of osteomyelitis, so that an ideal antimicrobial treatment can be administered since the very beginning of the therapy.

  12. Real time and label free profiling of clinically relevant exosomes

    Science.gov (United States)

    Sina, Abu Ali Ibn; Vaidyanathan, Ramanathan; Dey, Shuvashis; Carrascosa, Laura G.; Shiddiky, Muhammad J. A.; Trau, Matt

    2016-01-01

    Tumor-derived exosomes possess significant clinical relevance due to their unique composition of genetic and protein material that is representative of the parent tumor. Specific isolation as well as identification of proportions of these clinically relevant exosomes (CREs) from biological samples could help to better understand their clinical significance as cancer biomarkers. Herein, we present a simple approach for quantification of the proportion of CREs within the bulk exosome population isolated from patient serum. This proportion of CREs can potentially inform on the disease stage and enable non-invasive monitoring of inter-individual variations in tumor-receptor expression levels. Our approach utilises a Surface Plasmon Resonance (SPR) platform to quantify the proportion of CREs in a two-step strategy that involves (i) initial isolation of bulk exosome population using tetraspanin biomarkers (i.e., CD9, CD63), and (ii) subsequent detection of CREs within the captured bulk exosomes using tumor-specific markers (e.g., human epidermal growth factor receptor 2 (HER2)). We demonstrate the isolation of bulk exosome population and detection of as low as 10% HER2(+) exosomes from samples containing designated proportions of HER2(+) BT474 and HER2(−) MDA-MB-231 cell derived exosomes. We also demonstrate the successful isolation of exosomes from a small cohort of breast cancer patient samples and identified that approximately 14–35% of their bulk population express HER2. PMID:27464736

  13. Clinical and molecular characteristics of pyometra in female dogs.

    Science.gov (United States)

    Hagman, R

    2012-12-01

    Pyometra is a common disease of female dogs. In Sweden, where approximately 90% of the dog population is intact (not neutered), nearly 25% of all female dogs are diagnosed with the disease before 10 years of age. In certain high-risk breeds, this risk of developing pyometra exceeds 50%. Various clinical signs associated with the genital tract as well as with systemic disease are present in dogs with pyometra. A frequent and serious consequence of the uterine infection is endotoxaemia and progression into the systemic inflammatory response syndrome (SIRS), or sepsis, and the disease is then regarded as a medical emergency. Acute phase proteins and inflammatory markers associated with SIRS and with the outcome as measured by length of hospitalization have been identified in blood samples. Recently, the inflammatory response in infected uterine tissue during pyometra has been more closely explored. The expression of many genes associated with chemokines, cytokines, inflammatory cell extravasation, anti-bacterial action, the complement system and innate immune responses and also a large panel of proteases are upregulated in the uterine tissue in pyometra. Products of certain upregulated genes may be detected systemically and used for diagnostic or prognostic purposes provided that tests are developed in the future. More knowledge of the complex local and systemic inflammatory response in pyometra may allow identification of novel disease biomarkers or future targets for treatment. In this article, clinical as well as molecular characteristics of the disease are reviewed. PMID:23279529

  14. Acute kidney injury: from clinical to molecular diagnosis.

    Science.gov (United States)

    Ronco, Claudio

    2016-01-01

    The RIFLE classification was introduced in 2004 to describe the presence of acute kidney injury (AKI) and to define its clinical stage, based upon the serum creatinine level and urine output. The same criteria, although slightly modified, are used in the other scoring systems AKIN and KDIGO. Mortality and morbidity remain high in AKI, suggesting that current diagnostic methods are suboptimal, poorly accurate, and often timely inadequate in detecting the presence of early kidney injury. Conversely, a growing body of evidence indicates that new AKI biomarkers can be used to both rule out AKI and to assess high-risk conditions or the presence of subclinical forms. Neutrophil gelatinase-associated lipocalin or cell cycle arrest biomarkers seem to be sensitive and specific enough to be used in conjunction with existing markers of AKI for better classifying renal injury as well as dysfunction. Improvements in diagnosis, risk identification, stratification, prognosis, and therapeutic monitoring may improve prevention and protection from organ damage and help to identify patients at risk, allowing individualized therapy. In this view, we may say that AKI diagnosis has finally moved from clinical to molecular level with potential benefits for the patients because similar progress has been shown in other disciplines. PMID:27384344

  15. Clinical presentations and biochemical profile in adult celiac disease patients in Hyderabad: Pakistan

    OpenAIRE

    Masood, Naila; Ali Shaikh, Imran

    2014-01-01

    Objective: To see the various clinical presentations and biochemical profile in adult celiac disease patients of Hyderabad Sindh. Methods: A total 60 suspected cases of adult celiac disease, both males and females were screened out from Liaquat University of Medical and Health Sciences hospital and private clinics at Sadar Hyderabad Sind by non probability purposive sampling during a period from July 2011 to December 2012.Age ranged between 18 to 55 Years. A detailed history and clinical exam...

  16. Automated Analysis and Classification of Histological Tissue Features by Multi-Dimensional Microscopic Molecular Profiling.

    Directory of Open Access Journals (Sweden)

    Daniel P Riordan

    Full Text Available Characterization of the molecular attributes and spatial arrangements of cells and features within complex human tissues provides a critical basis for understanding processes involved in development and disease. Moreover, the ability to automate steps in the analysis and interpretation of histological images that currently require manual inspection by pathologists could revolutionize medical diagnostics. Toward this end, we developed a new imaging approach called multidimensional microscopic molecular profiling (MMMP that can measure several independent molecular properties in situ at subcellular resolution for the same tissue specimen. MMMP involves repeated cycles of antibody or histochemical staining, imaging, and signal removal, which ultimately can generate information analogous to a multidimensional flow cytometry analysis on intact tissue sections. We performed a MMMP analysis on a tissue microarray containing a diverse set of 102 human tissues using a panel of 15 informative antibody and 5 histochemical stains plus DAPI. Large-scale unsupervised analysis of MMMP data, and visualization of the resulting classifications, identified molecular profiles that were associated with functional tissue features. We then directly annotated H&E images from this MMMP series such that canonical histological features of interest (e.g. blood vessels, epithelium, red blood cells were individually labeled. By integrating image annotation data, we identified molecular signatures that were associated with specific histological annotations and we developed statistical models for automatically classifying these features. The classification accuracy for automated histology labeling was objectively evaluated using a cross-validation strategy, and significant accuracy (with a median per-pixel rate of 77% per feature from 15 annotated samples for de novo feature prediction was obtained. These results suggest that high-dimensional profiling may advance the

  17. Angelman syndrome: review of clinical and molecular aspects

    Directory of Open Access Journals (Sweden)

    Bird LM

    2014-05-01

    Full Text Available Lynne M Bird1Department of Pediatrics, University of California, Division of Genetics, Rady Children’s Hospital, San Diego, California, USAAbstract: “Angelman syndrome” (AS is a neurodevelopmental disorder whose main features are intellectual disability, lack of speech, seizures, and a characteristic behavioral profile. The behavioral features of AS include a happy demeanor, easily provoked laughter, short attention span, hypermotoric behavior, mouthing of objects, sleep disturbance, and an affinity for water. Microcephaly and subtle dysmorphic features, as well as ataxia and other movement disturbances, are additional features seen in most affected individuals. AS is due to deficient expression of the ubiquitin protein ligase E3A (UBE3A gene, which displays paternal imprinting. There are four molecular classes of AS, and some genotype–phenotype correlations have emerged. Much remains to be understood regarding how insufficiency of E6-AP, the protein product of UBE3A, results in the observed neurodevelopmental deficits. Studies of mouse models of AS have implicated UBE3A in experience-dependent synaptic remodeling.Keywords: Angelman syndrome, chromosome 15q11-13, UBE3A, imprinting

  18. Twenty-Year Survival in Glioblastoma: A Case Report and Molecular Profile

    International Nuclear Information System (INIS)

    Background: The prognosis for patients with glioblastoma (GB) remains grim. Historically, the median survival has been 6 to 9 months. Recent research has improved the outcome slightly. A computer search of the literature reveals few long-term survivors. Method: Presented here is a case report of a 20-year survivor of GB, with pathologic review to confirm the diagnosis. A battery of molecular studies was performed to develop a molecular profile of this unique patient. Results: The results of the molecular genetic testing for this most unusual patient were as follows: (1) methylguanine methyl transferase (MGMT) was methylated, (2) p53 positive, (3) PTEN tumor suppressor gene positive, (4) protein kinase AKT (pAKT) negative, and (5) epidermal growth factor receptor negative. Conclusion: To our knowledge, this is the longest survival of any patient in the literature whose initial diagnosis was GB. Triple-positive GBM patients (MGMT methylated, PTEN, and p53 positive) are uncommon but may be associated with a better prognosis. Further research is needed to confirm whether this molecular profile is prognostic of prolonged survival. Molecular genetics will determine future treatment and prognosis in GB.

  19. Friedreich's ataxia: clinical and molecular study of 25 Brazilian cases

    Directory of Open Access Journals (Sweden)

    Albano Lilian M. J.

    2001-01-01

    Full Text Available INTRODUCTION: Friedreich's ataxia is a neurodegenerative disorder whose clinical diagnostic criteria for typical cases basically include: a early age of onset (< 20 or 25 years, b autosomal recessive inheritance, c progressive ataxia of limbs and gait, and d absence of lower limb tendon reflexes. METHODS: We studied the frequency and the size of expanded GAA and their influence on neurologic findings, age at onset, and disease progression in 25 Brazilian patients with clinical diagnosis of Friedreich's ataxia - 19 typical and 6 atypical - using a long-range PCR test. RESULTS: Abnormalities in cerebellar signs, in electrocardiography, and pes cavus occurred more frequently in typical cases; however, plantar response and speech were more frequently normal in this group when the both typical and atypical cases were compared. Homozygous GAA expansion repeats were detected in 17 cases (68% - all typical cases. In 8 patients (32% (6 atypical and 2 typical, no expansion was observed, ruling out the diagnosis of Friedreich's ataxia. In cases with GAA expansions, foot deformity, cardiac abnormalities, and some neurologic findings occurred more frequently; however, abnormalities in cranial nerves and in tomographic findings were detected less frequently than in patients without GAA expansions. DISCUSSION: Molecular analysis was imperative for the diagnosis of Friedreich's ataxia, not only for typical cases but also for atypical ones. There was no genotype-phenotype correlation. Diagnosis based only on clinical findings is limited; however, it aids in better screening for suspected cases that should be tested. Evaluation for vitamin E deficiency is recommended, especially in cases without GAA expansion.

  20. Serrated polyposis syndrome: Molecular, pathological and clinical aspects

    Institute of Scientific and Technical Information of China (English)

    Carla Guarinos; Cristina Sánchez-Fortún; María Rodríguez-Soler; Cristina Alenda; Artemio Payá; Rodrigo Jover

    2012-01-01

    Hyperplastic polyps have traditionally been considered not to have malignant potential.New pathological classification of serrated polyps and recent discoveries about the serrated pathway of carcinogenesis have revolutionized the concepts and revitalized the research in this area.Until recently,it has been thought that most colorectal cancers arise from conventional adenomas via the traditional tumor suppressor pathway initiated by a mutation of the APC gene,but it has been found that this pathway accounts for only approximately 70%-80%of colorectal cancer (CRC) cases.The majority of the remaining colorectal cancer cases follow an alternative pathway leading to CpG island methylator phenotype carcinoma with BRAF mutation and with or without microsatellite instability.The mechanism of carcinomas arising from this alternative pathway seems to begin with an activating mutation of the BRAF oncogene.Serrated polyposis syndrome is a relatively rare condition characterized by multiple and/or large serrated polyps of the colon.Clinical characteristics,etiology and relationship of serrated polyposis syndrome to CRC have not been clarified yet.Patients with this syndrome show a high risk of CRC and both sporadic and hereditary cases have been described.Clinical criteria have been used for diagnosis and frequent colonoscopy surveillance should be performed in order to prevent colorectal cancer.In this review,we try to gather new insights into the molecular pathogenesis of serrated polyps in order to understand their possible clinical implications and to make an approach to the management of this syndrome.

  1. From Uniplex to Multiplex Molecular Profiling in Advanced Non-Small Cell Lung Carcinoma.

    Science.gov (United States)

    Ileana, Ecaterina E; Wistuba, Ignacio I; Izzo, Julie G

    2015-01-01

    Non-small cell lung carcinoma is a leading cause of cancer death worldwide. Understanding the molecular biology of survival and proliferation of cancer cells led to a new molecular classification of lung cancer and the development of targeted therapies with promising results. With the advances of image-guided biopsy techniques, tumor samples are becoming smaller, and the molecular testing techniques have to overcome the challenge of integrating the characterization of a panel of abnormalities including gene mutations, copy-number changes, and fusions in a reduced number of assays using only a small amount of genetic material. This article reviews the current knowledge about the most frequent actionable molecular abnormalities in non-small cell lung carcinoma, the new approaches of molecular analysis, and the implications of these findings in the context of clinical practice.

  2. Clinical profile of presumed and definitive ocular sarcoidosis

    Directory of Open Access Journals (Sweden)

    Jovanović Svetlana

    2013-01-01

    Full Text Available Introduction. Sarcoidosis is an antigen-mediated disease of unknown cause defined by granulomatous inflammation of different organs. Objective. The aim of this study was to analyze the clinical picture in 26 patients with a definitive and presumed ocular sarcoidosis. Methods. The following tests were conducted: angiotensin-converting enzyme, tuberculin skin test, liver enzymes and calcium in urine and serum. Enlarged hilar lymph glands were diagnosed using X-ray tomography or computed tomography of the mediastinum. A biopsy of lymph glands was performed either transbronchially or transmediastinally. Ophthalmic examination included biomicroscopic examination, intraocular pressure measurement, photofundus, fluorescein angiography, optical coherence tomography and computerized perimetry. Results. The average follow-up period of the disease was 6.1 years. The average age was 52.0 years. There were 62.5% female patients, with bilateral incidence of 69.2%. The clinical picture included: panuveitis (in 30.8% of patients, anterior uveitis (26.9%, posterior uveitis (26.9%, intermediate uveitis (7.7% and vitritis in (7.7%. The following complications were observed: cataract (in 34.6% of patients, cystoid macular edema (23.1%, glaucoma (15.4%, macroaneurysms (15.4%, neovascularization (7.7% and band keratopathy (3.8%. There was a statistically significant difference in the visual acuity (p=0.033 and severity of clinical symptoms (p=0.02 between the groups of patients with retinal vasculitis associated with “candle-wax” phenomenon and the group of patients with multiple chorioretinal lesions - “white dot” syndrome. Conclusion. To our consideration, the differences observed between the two groups are the result of retinal vasculitis and subsequent macular edema, which is significantly more frequent in the group with “candle-wax” phenomenon.

  3. Pigmented ameloblastic fibro-odontoma: clinical, histological, and immunohistochemical profile.

    Science.gov (United States)

    Martínez Martínez, Marisol; Romero, Celeste Sánchez; Piña, Alicia Rumayor; Palma Guzmán, José Mario; de Almeida, Oslei Paes

    2015-02-01

    Ameloblastic fibro-odontoma (AFO) is a slow-growing, expansive, benign odontogenic tumor, composed of ameloblastic epithelium embedded in an ectomesenchymal stroma resembling dental papilla, containing hard dental tissue in variable degrees of maturation, including enamel, dentin, and sometimes cementum. AFO typically affects the posterior mandible, causing bony expansion. We report a case of pigmented AFO in a 5-year-old boy, comprising clinical and histological features illustrated by immunohistochemistry using a large panel of antibodies, polarized light microscopy and scanning electron microscopy.

  4. Antimicrobial susceptibility profile of Neisseria gonorrhoeae at STI clinic

    Directory of Open Access Journals (Sweden)

    Shilpee C

    2008-01-01

    Full Text Available A total of 100 consecutive patients who attended a sexually transmitted infections clinic were studied. Thirteen had gonococcal urethritis, of which 10 showed growth of Neisseria gonorrhoeae on culture. All the isolates were tested for antimicrobial susceptibility by Australian Gonococcal Surveillance Programme (AGSP method and beta lactamase production by chromogenic cephalosporin test. Four patients were co-infected with each of the following: HIV, HBV and Chlamydia trachomatis . Gonococcal urethritis (13% was found more in male patients. Ten percent gonococcal isolates were penicillinase-producing N. gonorrhoeae , and another 10% were tetracycline-resistant N. gonorrhoeae .

  5. Molecular Biology of Pancreatic Cancer: How Useful Is It in Clinical Practice?

    OpenAIRE

    Sakorafas, George H; Vasileios Smyrniotis

    2012-01-01

    Context During the recent two decades dramatic advances of molecular biology allowed an in-depth understanding of pancreatic carcinogenesis. It is currently accepted that pancreatic cancer has a genetic component. The real challenge is now how these impressive advances could be used in clinical practice. Objective To critically present currently available data regarding clinical application of molecular biology in pancreatic cancer. Methods Reports about clinical implications of molecular bio...

  6. Protein expression profile and prevalence pattern of the molecular classes of breast cancer - a Saudi population based study

    International Nuclear Information System (INIS)

    Breast cancer is not a single entity but a diverse group of entities. Advances in gene expression profiling and immunohistochemistry as its surrogate marker have led to the unmasking of new breast cancer molecular subtypes, resulting in the emergence of more elaborate classification systems that are therapeutically and prognostically more predictive. Molecular class distribution across various ethnic groups may also reveal variations that can lead to different clinical outcomes in different populations. We aimed to analyze the spectrum of molecular subtypes present in the Saudi population. ER, PR, HER2, EGFR and CK5/6 were used as surrogate markers for gene expression profiling to classify 231 breast cancer specimens. Correlation of each molecular class with Ki-67 proliferation index, p53 mutation status, histologic type and grade of the tumor was also carried out. Out of 231 cases 9 (3.9%) were classified as luminal A (strong ER +ve, PR +ve or -ve), 37 (16%) as luminal B (weak to moderate ER +ve, and/or PR +ve), 40 (17.3%) as HER2+ (strong or moderately positive HER 2 with confirmation by silver enhanced in-situ hybridization) and 23 (10%) as basal (CK5/6 or EGFR +ve). Co-positivity of different markers in varied patterns was seen in 23 (10%) of cases which were grouped into a hybrid category comprising luminal B-HER2, HER2-basal and luminal-basal hybrids. Ninety nine (42.8%) of the tumors were negative for all five immunohistochemical markers and were labelled as unclassified (penta negative). A high Ki-67 proliferation index was seen in basal (p = 0.007) followed by HER2+ class. Overexpression of p53 was predominantly seen in HER2 + (p = 0.001) followed by the basal group of tumors. A strong correlation was noted between invasive lobular carcinoma and hormone receptor expression with 8 out of 9 lobular carcinoma cases (88.9%) classifiable as luminal cancers. Otherwise, there was no association between the molecular class and the histologic type or grade of the

  7. Protein expression profile and prevalence pattern of the molecular classes of breast cancer - a Saudi population based study

    Directory of Open Access Journals (Sweden)

    Hassan Ammar K

    2010-05-01

    Full Text Available Abstract Background Breast cancer is not a single entity but a diverse group of entities. Advances in gene expression profiling and immunohistochemistry as its surrogate marker have led to the unmasking of new breast cancer molecular subtypes, resulting in the emergence of more elaborate classification systems that are therapeutically and prognostically more predictive. Molecular class distribution across various ethnic groups may also reveal variations that can lead to different clinical outcomes in different populations. Methods We aimed to analyze the spectrum of molecular subtypes present in the Saudi population. ER, PR, HER2, EGFR and CK5/6 were used as surrogate markers for gene expression profiling to classify 231 breast cancer specimens. Correlation of each molecular class with Ki-67 proliferation index, p53 mutation status, histologic type and grade of the tumor was also carried out. Results Out of 231 cases 9 (3.9% were classified as luminal A (strong ER +ve, PR +ve or -ve, 37 (16% as luminal B (weak to moderate ER +ve, and/or PR +ve, 40 (17.3% as HER2+ (strong or moderately positive HER 2 with confirmation by silver enhanced in-situ hybridization and 23 (10% as basal (CK5/6 or EGFR +ve. Co-positivity of different markers in varied patterns was seen in 23 (10% of cases which were grouped into a hybrid category comprising luminal B-HER2, HER2-basal and luminal-basal hybrids. Ninety nine (42.8% of the tumors were negative for all five immunohistochemical markers and were labelled as unclassified (penta negative. A high Ki-67 proliferation index was seen in basal (p = 0.007 followed by HER2+ class. Overexpression of p53 was predominantly seen in HER2 + (p = 0.001 followed by the basal group of tumors. A strong correlation was noted between invasive lobular carcinoma and hormone receptor expression with 8 out of 9 lobular carcinoma cases (88.9% classifiable as luminal cancers. Otherwise, there was no association between the molecular class

  8. CLINICAL PROFILE OF CHILDHOOD POISONING IN A TERTIARY CARE CENTRE

    Directory of Open Access Journals (Sweden)

    Poornima

    2016-03-01

    Full Text Available BACKGROUND Accidents including poisoning are one of the leading causes of morbidity and mortality among children in the west. Poisoning, while never accounting for a large number of accidental deaths, have acquired prominence now because they have not decreased at the same rate as the infectious diseases. METHODS An observational study was done in Department of Paediatrics KIMS Bangalore to know the incidence and pattern of childhood poisoning, to know the morbidity and mortality resulting from childhood poisoning. 86 children aged between 0-18 years were admitted to the paediatric intensive care unit with history of poisoning during the 2-year period of the study (Nov 13-Nov 15 were included. Diagnosis of poisoning was made on the basis of history and examination findings, Relevant investigations were done and Profile of patients with poisoning, their symptoms, type of poisoning and outcome were analysed. RESULTS The average duration of stay in the hospital was 2.7 days. Poisoning was accidental in 80 (93% patients whereas suicidal intent was present in only 6 (7% patients. Total 5 (5.8% patients died of which 4 were due to insecticide and pesticide poisoning and one was due to kerosene poisoning. CONCLUSION In the present study the probable reason for higher incidence of poisoning by insecticides & pesticides could be the involvement of higher age group and more involvement of adolescent children.

  9. Molecular Profiling of Multiplexed Gene Markers to Assess Viability of Ex Vivo Human Colon Explant Cultures

    OpenAIRE

    Drew, Janice E.; Andrew J Farquharson; Vase, Hollie; Carey, Frank A.; Steele, Robert J C; Ross, Ruth A; Bunton, David C.

    2015-01-01

    Abstract Human colon tissue explant culture provides a physiologically relevant model system to study human gut biology. However, the small (20–30 mg) and complex tissue samples used present challenges for monitoring tissue stability, viability, and provision of sufficient tissue for analyses. Combining molecular profiling with explant culture has potential to overcome such limitations, permitting interrogation of complex gene regulation required to maintain gut mucosa in culture, monitor res...

  10. Molecular Forensic Profiling of Cryptosporidium Species and Genotypes in Raw Water

    OpenAIRE

    Ruecker, Norma J.; Bounsombath, Niravanh; Wallis, Peter; Ong, Corinne S. L.; Isaac-Renton, Judith L.; Neumann, Norman F.

    2005-01-01

    The emerging concept of host specificity of Cryptosporidium spp. was exploited to characterize sources of fecal contamination in a watershed. A method of molecular forensic profiling of Cryptosporidium oocysts on microscope slides prepared from raw water samples processed by U.S. Environmental Protection Agency Method 1623 was developed. The method was based on a repetitive nested PCR-restriction fragment length polymorphism-DNA sequencing approach that permitted the resolution of multiple sp...

  11. STUDY OF CLINICAL PROFILE OF NON - TOXIC GOITER WITH SPECIAL REFERENCE TO CORRELATION OF PATHOLOGY, LIPID PROFILE AND ANTIBODY LEVEL

    Directory of Open Access Journals (Sweden)

    Santanu

    2014-11-01

    Full Text Available OBJECTIVE : To evaluate the morphology of non - toxic goiter , the role of auto - immunity and lipid abnormalities in overt and sub - clinical hypothyroid goiter patients. METHODS: A descriptive observational study was undertaken amongst goiter patients without thyrotoxic features comprising 50 randomly selected cases within the range of 12 - 65years. Goiter patients with thyrotoxic features , acute illness and other visceral diseases were excluded. The patients were evaluated with thyroid function tests , USG - thyroid , FNAC - thyroid , anti - TPO and lipid profile after thorough clinical examination. RESULTS : In my study , most patients were female (with male: female ratio 1:5.25 and were middle aged (betwe en age group 30 - 49years. Among all patients 60 %( i.e . 30 patients had Hashimoto’s thyroiditis , 24% (i.e. 12 patients had diffuse colloid goiter and 16% (i.e. 8 patients had nodular goiter. 52% (i.e. 26 of all patients and 76.6% (i.e. 23 of Hashimoto ’s goiter patients were anti - TPO positive. Majority of colloid goiter (i.e. 66.7% and nodular goiter (50% patients were euthyroid but majority of Hashimoto’s goiter patients were hypothyroid (65.38% overt and 33% sub - clinical. Majority of anti - TPO posit ive patients were hypothyroid (65.38% overt and 30.62% sub - clinical and majority of anti - TPO negative patients (66.67% were euthyroid. Within reference range of TSH , there was a linear increase in total serum cholesterol , LDL - cholesterol , triglyceride an d decrease in HDL - cholesterol with increase in TSH. This lipid profile changes are mainly seen in Hashimoto goiter patients . CONCLUSION : this study emphasizes the role of auto - immunity in non - toxic goiter patients especially Hashimoto’s thyroiditis patient s and lipid profile changes in those patients.

  12. An Efficient Molecular Dynamics Scheme for the Calculation of Dopant Profiles due to Ion Implantation

    CERN Document Server

    Beardmore, K M; Beardmore, Keith M.; Gronbech-Jensen, Niels

    1998-01-01

    We present a highly efficient molecular dynamics scheme for calculating the concentration depth profile of dopants in ion irradiated materials. The scheme incorporates several methods for reducing the computational overhead, plus a rare event algorithm that allows statistically reliable results to be obtained over a range of several orders of magnitude in the dopant concentration. We give examples of using this scheme for calculating concentration profiles of dopants in crystalline silicon. Here we can predict the experimental profile over five orders of magnitude for both channeling and non-channeling implants at energies up to 100s of keV. The scheme has advantages over binary collision approximation (BCA) simulations, in that it does not rely on a large set of empirically fitted parameters. Although our scheme has a greater computational overhead than the BCA, it is far superior in the low ion energy regime, where the BCA scheme becomes invalid.

  13. Time-course profiling of molecular stress responses to silver nanoparticles in the earthworm Eisenia fetida.

    Science.gov (United States)

    Hayashi, Yuya; Heckmann, Lars-Henrik; Simonsen, Vibeke; Scott-Fordsmand, Janeck J

    2013-12-01

    The molecular mechanism of silver nanoparticle (AgNP) toxicity, particularly its temporal aspect, is currently limited in the literature. This study seeks to identify and profile changes in molecular response patterns over time during soil exposure of the earthworm Eisenia fetida to AgNPs (82±27 nm) with reference to dissolved silver salt (AgNO₃). Principal component analysis of selected gene and enzyme response profiles revealed dissimilar patterns between AgNO₃ and AgNP treatments and also over time. Despite the observed difference in molecular profiles, the body burdens of total Ag were within the same range (10-40 mg/kg dry weight worm) for both treatments with apparent correlation to the induction pattern of metallothionein. AgNO₃ induced the genes and enzymes related to oxidative stress at day 1, after which markers of energy metabolism were all suppressed at day 2. Exposure to AgNPs likewise led to induction of oxidative stress genes at day 2, but with a temporal pattern shift to immune genes at day 14 following metabolic upregulation at day 7. The involvement of oxidative stress and subsequent alterations in immune gene regulation were as predicted by our in vitro study reported previously, highlighting the importance of immunological endpoints in nanosilver toxicity. PMID:24041528

  14. X-linked acrogigantism syndrome: clinical profile and therapeutic responses.

    Science.gov (United States)

    Beckers, Albert; Lodish, Maya Beth; Trivellin, Giampaolo; Rostomyan, Liliya; Lee, Misu; Faucz, Fabio R; Yuan, Bo; Choong, Catherine S; Caberg, Jean-Hubert; Verrua, Elisa; Naves, Luciana Ansaneli; Cheetham, Tim D; Young, Jacques; Lysy, Philippe A; Petrossians, Patrick; Cotterill, Andrew; Shah, Nalini Samir; Metzger, Daniel; Castermans, Emilie; Ambrosio, Maria Rosaria; Villa, Chiara; Strebkova, Natalia; Mazerkina, Nadia; Gaillard, Stéphan; Barra, Gustavo Barcelos; Casulari, Luis Augusto; Neggers, Sebastian J; Salvatori, Roberto; Jaffrain-Rea, Marie-Lise; Zacharin, Margaret; Santamaria, Beatriz Lecumberri; Zacharieva, Sabina; Lim, Ee Mun; Mantovani, Giovanna; Zatelli, Maria Chaira; Collins, Michael T; Bonneville, Jean-François; Quezado, Martha; Chittiboina, Prashant; Oldfield, Edward H; Bours, Vincent; Liu, Pengfei; W de Herder, Wouter; Pellegata, Natalia; Lupski, James R; Daly, Adrian F; Stratakis, Constantine A

    2015-06-01

    X-linked acrogigantism (X-LAG) is a new syndrome of pituitary gigantism, caused by microduplications on chromosome Xq26.3, encompassing the gene GPR101, which is highly upregulated in pituitary tumors. We conducted this study to explore the clinical, radiological, and hormonal phenotype and responses to therapy in patients with X-LAG syndrome. The study included 18 patients (13 sporadic) with X-LAG and microduplication of chromosome Xq26.3. All sporadic cases had unique duplications and the inheritance pattern in two families was dominant, with all Xq26.3 duplication carriers being affected. Patients began to grow rapidly as early as 2-3 months of age (median 12 months). At diagnosis (median delay 27 months), patients had a median height and weight standard deviation scores (SDS) of >+3.9 SDS. Apart from the increased overall body size, the children had acromegalic symptoms including acral enlargement and facial coarsening. More than a third of cases had increased appetite. Patients had marked hypersecretion of GH/IGF1 and usually prolactin, due to a pituitary macroadenoma or hyperplasia. Primary neurosurgical control was achieved with extensive anterior pituitary resection, but postoperative hypopituitarism was frequent. Control with somatostatin analogs was not readily achieved despite moderate to high levels of expression of somatostatin receptor subtype-2 in tumor tissue. Postoperative use of adjuvant pegvisomant resulted in control of IGF1 in all five cases where it was employed. X-LAG is a new infant-onset gigantism syndrome that has a severe clinical phenotype leading to challenging disease management.

  15. Pulmonary involvement in systemic sclerosis: A clinical profile

    Directory of Open Access Journals (Sweden)

    A S Deepa

    2016-01-01

    Full Text Available Background: Systemic sclerosis is a generalized disorder of connective tissue affecting skin and internal organs. Lung involvement accounts for significant morbidity and is a leading cause of mortality in patients. Objectives: This study intends to study the frequency of occurrence of pulmonary involvement in progressive systemic sclerosis (PSS and to describe the clinical and radiological picture of pulmonary involvement in PSS. Materials and Methods: This was a descriptive cross-sectional study. A detailed history, modified Rodnan score, clinical examination, routine investigation, antinuclear antibody, immuno biot, chest X-ray (CXR, pulmonary function test (PFT, and 6 min walk test (6MWT were performed on all patients. High resolution computed tomography was done on those who consented. Results: Hundred subjects with PSS were included in the study; 90 were females and 10 were males. Common presenting complaints were skin thickening in 98% and Raynaud's phenomenon in 98%. Skin thickening of digits beyond metacarpo phalangeal was seen in 98%, face and neck in 92%, and hands in 92%. Chest wall thickening was seen in 40 subjects (40%. 90 (90% of the studied subjects had pulmonary involvement, longer duration of disease was significantly associated with pulmonary involvement (P < 0.05. Dyspnea, cough, bilateral crepitations, CXR, Borg score, and Rodnan score was found to be significantly associated with severe pulmonary involvement (P < 0.05. Conclusion: The prevalence of pulmonary involvement in this cohort study was 90%. Almost 1/3rd of patients, that is 29 (29% were detected to have pulmonary involvement despite being asymptomatic for respiratory complaints, hence early screening and evaluation is recommended. PFT and 6MWT are noninvasive, cost-effective, and easily available screening tests which can be used in resource-limited settings.

  16. Lobular breast cancer: Clinical, molecular and morphological characteristics.

    Science.gov (United States)

    Christgen, Matthias; Steinemann, Doris; Kühnle, Elna; Länger, Florian; Gluz, Oleg; Harbeck, Nadia; Kreipe, Hans

    2016-07-01

    Infiltrating lobular breast cancer (ILBC) is the most common special breast cancer subtype. This review provides a comprehensive description of ILBC characteristics, including epidemiology, clinical features, molecular genetics and histomorphology. Twenty detailed supplemental data tables guide through primary data of more than 200 original studies. Meta-analyses indicate that ILBC is at least twice as common in the Western world as it is in other geographic regions. ILBC is over-represented in so-called interval carcinomas and in primary metastatic breast cancer. ILBC is also associated higher age, higher pT stage and hormone receptor (ER/PR) positivity. Pathological complete response rates after neoadjuvant chemotherapy are low, ranging between 0% and 11%. Positive resection margins after breast-conserving surgery are comparatively frequent and 17% to 65% of patients undergo a second surgical intervention. Depending on the morphological stringency in the diagnosis of ILBC, lack of E-cadherin expression is observed in 55% to 100% of cases. CDH1/E-cadherin mutation detection rates vary between 12% and 83%. Various additional molecular factors, including PIK3CA, TP53, FOXA1, FGFR1, ZNF703 and BCAR4, have been implicated in ILBC or progression of lobular carcinoma in situ (LCIS) to invasive cancer and are discussed in detail. Eight instructive figure plates recapitulate the histomorphology of ILBC and its variants. Furthermore, we draw attention to rarely addressed histological details, such as two-sided nuclear compression and fat-avoiding growth at the invasion front. Last but not least, we discuss future translational research directions and emphasize the concept of synthetic lethality, which promises new options for targeted ILBC therapy.

  17. Peripheral Blood Monocyte Gene Expression Profile Clinically Stratifies Patients With Recent-Onset Type 1 Diabetes

    OpenAIRE

    Irvine, Katharine M.; Gallego, Patricia; An, Xiaoyu; Best, Shannon E.; Thomas, Gethin; Wells, Christine; Harris, Mark; Cotterill, Andrew; Thomas, Ranjeny

    2012-01-01

    Novel biomarkers of disease progression after type 1 diabetes onset are needed. We profiled peripheral blood (PB) monocyte gene expression in six healthy subjects and 16 children with type 1 diabetes diagnosed ∼3 months previously and analyzed clinical features from diagnosis to 1 year. Monocyte expression profiles clustered into two distinct subgroups, representing mild and severe deviation from healthy control subjects, along the same continuum. Patients with strongly divergent monocyte gen...

  18. CLINICAL AND MANAGEMENT PROFILE OF HYPONATRAEMIA IN A TERTIARY HOSPITAL

    Directory of Open Access Journals (Sweden)

    Bishwaranjan Mohanty

    2016-07-01

    Full Text Available Hyponatraemia is an electrolyte disorder defined by blood sodium level < 135 mmol/L. It is a clinical emergency. It may be acute or chronic depending on duration and may be hypervolaemic, euvolaemic or hypovolaemic. In this observational study, a total of 111 patients were included. Out of them, 75% were male and 25% were female. Most patients were of 4 th decade (72%. Among them, 22% in CKD stage II, 24% in stage III, 29% in stage IV and 25% were in stage V and 75% of patients presented with acute and severe hyponatraemia. Hiccup (38% was the major symptom, followed by vomiting, dehydration, confusion. Among the modes of treatment used, 3% hypertonic saline was used in majority. Duration of treatment in acute and chronic hyponatraemia was average of 3 and 5 days respectively. Despite judicious treatment, 1 patient developed symptoms and signs of demyelination on next day of treatment. Patient was treated with Inj. methylprednisolone. Among the chronic hyponatraemia patients, 1 patient suffered from extrapontine myelinosis who recovered with supportive treatment. About 66% patients presented with hypovolaemic hyponatraemia due to exacerbating factors such as vomiting, infection, injudicious use of diuretic, dehydration of unknown cause.

  19. Clinical and molecular epidemiology of neonatal leukemia in Brazil.

    Science.gov (United States)

    Moura, Suellen Valadares; Andrade, Francianne; Magalhães, Isis Q; Costa, Imaruí; Silva, Denise Bousfield; D'Andrea, Maria Lydia; Pinheiro, Vitória P; Lee, Maria Lucia M; Werneck, Fernando; Emerenciano, Mariana; Pombo-de-Oliveira, Maria S

    2015-04-01

    The clinical and molecular findings of 77 cases of neonatal leukemia (NL) and 380 of infant leukemia (IL) were selected to distinguish features between NL and IL. Somatic gene mutations associated with acute leukemia including FLT3, RAS and PTPN11 were revisited. There were 42 cases of congenital leukemia associated with Down syndrome (DS) and 39 of these cases presented features of acute myeloid leukemia (AML)-M7. Twenty-seven of the DS cases underwent spontaneous remission and were reclassified as a transient myeloproliferative disorder. GATA1 mutations were found in 70% of these cases. In non-DS, frequent abnormalities were MLL rearrangements, mainly MLL-AFF1 in acute lymphoblastic leukemia and MLL-MLLT3 in AML. The FLT3 mutation was not found, while RAS (n = 4) and PTPN11 (n = 2) mutations were identified and reported for the first time in NL. There was substantial evidence to support that somatic abnormalities occur in utero. Thus, congenital leukemia is a good model for understanding leukemogenesis.

  20. Clinical profile of gastric cancer in Khuzestan, southwest of Iran

    Institute of Scientific and Technical Information of China (English)

    Hajiani Eskandar; Sarmast Shoshtari Mohammad Hossein; Masjedizadeh Rahim; Hashemi Jalal; Azmi Mehrdad; Tahereh Rajabi

    2006-01-01

    AIM: To analyze the characteristics of epidemiological, clinical and survival patterns among patients with carcinoma of the stomach. METHODS: We retrospectively studied the characteristics of 186 gastric adenocarcinoma patients at Ahwaz Jundishapur University Hospitals (AJSUH) from September 1, 1996 to September 1, 2002. All the patients had histopathologicallyconfirmed malignancy. Demographic variables, family history of gastric cancer (GC), clinicopathologic characteristics and treatment-related variables were analyzed. Univariate analysis was performed with the log-rank test and multivariate analysis with Cox regression. P < 0.05 was considered statistically significant. RESULTS: Male to female ratio was 2.6:1. The meanage was 60.6 years and 14% of the patients were younger than 40 years. Adenocarcinoma, gastric lymphoma, and gastric metastasis were found in 94.5%,2.3%, and 3% patients, respectively. There was an average of 6-mo delay between the initial symptoms and the diagnosis. Among adenocarcinoma groups, intestinal type was the commonest (55.9%) and the distal third was the most common localization (88.4%). One hundred and thirty-four patients (72.1%) were males. Thirty-one patients (17%) had a family history of GC. Surgery was performed in 90% of patients (non-curative).CONCLUSION: The epidemiological features of GC in south Iran mimic those in high-risk areas. There is a higher frequency of GC in young patients at our institution. Patients are detected and treated after a relatively long delay. Most patients present in advanced stages, which favors a poor overall survival. Family history of GC has a significant problem in our area. Studying the etiology of this cancer in south Iran and earlier diagnosis and subsequent better cares are recommended.

  1. PNH revisited: Clinical profile, laboratory diagnosis and follow-up

    Directory of Open Access Journals (Sweden)

    Gupta P

    2009-01-01

    Full Text Available Background: Paroxysmal nocturnal hemoglobinuria (PNH is characterized by intravascular hemolysis, marrow failure, nocturnal hemoglobinuria and thrombophila. This acquired disease caused by a deficiency of glycosylphosphatidylinositol (GPI anchored proteins on the hematopoietic cells is uncommon in the Indian population. Materials and Methods: Data of patients diagnosed with PNH in the past 1 year were collected. Clinical data (age, gender, various presenting symptoms, treatment information and follow-up data were collected from medical records. Results of relevant diagnostic tests were documented i.e., urine analysis, Ham′s test, sucrose lysis test and sephacryl gel card test (GCT for CD55 and CD59. Results: A total of 5 patients were diagnosed with PNH in the past 1 year. Presenting symptoms were hemolytic anemia (n=4 and bone marrow failure (n=1. A GCT detected CD59 deficiency in all erythrocytes in 4 patients and CD55 deficiency in 2 patients. A weak positive PNH test for CD59 was seen in 1 patient and a weak positive PNH test for CD55 was seen in 3 patients. All patients were negative by sucrose lysis test. Ham′s test was positive in two cases. Patients were treated with prednisolone and/or androgen and 1 patient with aplastic anemia was also given antithymocyte globulin. A total of 4 patients responded with a partial recovery of hematopoiesis and 1 patient showed no recovery. None of the patients received a bone marrow transplant. Conclusion: The study highlights the diagnostic methods and treatment protocols undertaken to evaluate the PNH clone in a developing country where advanced methods like flowcytometry immunophenotyping (FCMI and bone marrow transplants are not routinely available.

  2. Neuromyotonia: Clinical profile of twenty cases from northwest India

    Directory of Open Access Journals (Sweden)

    Panagariya Ashok

    2006-01-01

    Full Text Available Objectives: We are presenting 20 cases of the intriguing clinico-electromyographic entity, now considered a potassium channel disorder, Neuromyotonia. Our experience with the clinical manifestations, underlying abnormalities and response to various therapies is documented. Materials and Methods: Patients with diffuse pain or undulating muscle movements, with or without stiffness were sent for electromyographic and further studies. Patients with "neuromyotonic discharges" were included after exclusion of hypocalcaemia. Results: Our cases included 19 males and one female of age group 15 to 52 years, the majority being between 30 to 45 years. Undulating movements were seen in 19, of which two had focal twitching. Muscle stiffness was a complaint in five; pain was the chief presenting complaint of 19, which started in the calf in all. Irritability, insomnia and a peculiar worried pinched face were present in 12 patients. CSF was abnormal with mildly raised protein in eight. Curiously, 11 of these patients had taken ayurvedic treatment for various complaints in the preceding one month. Bell′s palsy was associated in four, peripheral neuropathy in two and residual poliomyelitis in two. Electromyographic evidence of spontaneous activity in the form of "neuromyotonic discharges" was seen in all. Antibodies to voltage gated potassium channels was tested in one patient and was positive (titer was 1028 pM. Membrane stabilizers (e.g., phenytoin sodium in our experience did not provide adequate rapid relief; we tried high-dose intravenous Methylprednisolone in 19 with significant amelioration of complaints. One patient was offered intravenous immunoglobulin, to which he responded. Conclusions: Neuromyotonia is a heterogeneous condition and can present in varied ways including diffuse nonspecific pain. This uncommon condition is potentially treatable and can be picked up with high index of suspicion.

  3. Univariate and multivariate molecular spectral analyses of lipid related molecular structural components in relation to nutrient profile in feed and food mixtures

    Science.gov (United States)

    Abeysekara, Saman; Damiran, Daalkhaijav; Yu, Peiqiang

    2013-02-01

    The objectives of this study were (i) to determine lipid related molecular structures components (functional groups) in feed combination of cereal grain (barley, Hordeum vulgare) and wheat (Triticum aestivum) based dried distillers grain solubles (wheat DDGSs) from bioethanol processing at five different combination ratios using univariate and multivariate molecular spectral analyses with infrared Fourier transform molecular spectroscopy, and (ii) to correlate lipid-related molecular-functional structure spectral profile to nutrient profiles. The spectral intensity of (i) CH3 asymmetric, CH2 asymmetric, CH3 symmetric and CH2 symmetric groups, (ii) unsaturation (Cdbnd C) group, and (iii) carbonyl ester (Cdbnd O) group were determined. Spectral differences of functional groups were detected by hierarchical cluster analysis (HCA) and principal components analysis (PCA). The results showed that the combination treatments significantly inflicted modifications (P molecular spectral intensity (CH2 asymmetric stretching peak height, CH2 symmetric stretching peak height, ratio of CH2 to CH3 symmetric stretching peak intensity, and carbonyl peak area). Ratio of CH2 to CH3 symmetric stretching peak intensity, and carbonyl peak significantly correlated with nutrient profiles. Both PCA and HCA differentiated lipid-related spectrum. In conclusion, the changes of lipid molecular structure spectral profiles through feed combination could be detected using molecular spectroscopy. These changes were associated with nutrient profiles and functionality.

  4. Prediction of Clinically Relevant Safety Signals of Nephrotoxicity through Plasma Metabolite Profiling

    Directory of Open Access Journals (Sweden)

    W. B. Mattes

    2013-01-01

    Full Text Available Addressing safety concerns such as drug-induced kidney injury (DIKI early in the drug pharmaceutical development process ensures both patient safety and efficient clinical development. We describe a unique adjunct to standard safety assessment wherein the metabolite profile of treated animals is compared with the MetaMap Tox metabolomics database in order to predict the potential for a wide variety of adverse events, including DIKI. To examine this approach, a study of five compounds (phenytoin, cyclosporin A, doxorubicin, captopril, and lisinopril was initiated by the Technology Evaluation Consortium under the auspices of the Drug Safety Executive Council (DSEC. The metabolite profiles for rats treated with these compounds matched established reference patterns in the MetaMap Tox metabolomics database indicative of each compound’s well-described clinical toxicities. For example, the DIKI associated with cyclosporine A and doxorubicin was correctly predicted by metabolite profiling, while no evidence for DIKI was found for phenytoin, consistent with its clinical picture. In some cases the clinical toxicity (hepatotoxicity, not generally seen in animal studies, was detected with MetaMap Tox. Thus metabolite profiling coupled with the MetaMap Tox metabolomics database offers a unique and powerful approach for augmenting safety assessment and avoiding clinical adverse events such as DIKI.

  5. Molecular imaging of prostate cancer: translating molecular biology approaches into the clinical realm

    Energy Technology Data Exchange (ETDEWEB)

    Vargas, Hebert Alberto; Sala, Evis; Hricak, Hedvig [Memorial Sloan Kettering Cancer Center, Department of Radiology, New York, NY (United States); Grimm, Jan [Memorial Sloan Kettering Cancer Center, Department of Radiology, New York, NY (United States); Program in Molecular Pharmacology and Chemistry, Memorial Sloan Kettering Cancer Center, New York (United States); Donati, Olivio F. [Memorial Sloan Kettering Cancer Center, Department of Radiology, New York, NY (United States); University Hospital Zurich, Institute of Diagnostic and Interventional Radiology, Zurich (Switzerland)

    2015-05-01

    The epidemiology of prostate cancer has dramatically changed since the introduction of prostate-specific antigen (PSA) screening in the 1980's. Most prostate cancers today are detected at early stages of the disease and are considered 'indolent'; however, some patients' prostate cancers demonstrate a more aggressive behaviour which leads to rapid progression and death. Increasing understanding of the biology underlying the heterogeneity that characterises this disease has led to a continuously evolving role of imaging in the management of prostate cancer. Functional and metabolic imaging techniques are gaining importance as the impact on the therapeutic paradigm has shifted from structural tumour detection alone to distinguishing patients with indolent tumours that can be managed conservatively (e.g., by active surveillance) from patients with more aggressive tumours that may require definitive treatment with surgery or radiation. In this review, we discuss advanced imaging techniques that allow direct visualisation of molecular interactions relevant to prostate cancer and their potential for translation to the clinical setting in the near future. The potential use of imaging to follow molecular events during drug therapy as well as the use of imaging agents for therapeutic purposes will also be discussed. (orig.)

  6. Profile of a Liver Transplant Follow-Up Clinic in a Nontransplant Canadian Urban Centre

    OpenAIRE

    Bazylewski, R; Rosser, BG; Cohen, A; Kaita, KDE; Minuk, GY

    1997-01-01

    Care of the growing number of liver transplant recipients will increasingly fall on the referring centres. Thus, there is a need to define more clearly the demographic, clinical and laboratory profiles of liver transplant recipients, particularly in the setting of a centre where a liver transplantation program does not exist. The present study documented these features in 37 patients attending an adult ambulatory care clinic in an urban, nonliver transplant centre. Mean ± SD age of the study ...

  7. Clinical Profile and Outcome of Japanese Encephalitis in Children Admitted with Acute Encephalitis Syndrome

    OpenAIRE

    Gitali Kakoti; Prafulla Dutta; Bishnu Ram Das; Jani Borah; Jagadish Mahanta

    2013-01-01

    Japanese encephalitis (JE) is an arthropod borne viral disease. Children are most commonly affected in Southeast Asian region showing symptoms of central nervous system with several complications and death. The clinical characteristics and outcomes in pediatric JE patients hospitalized with acute encephalitis syndrome (AES) are still poorly understood. A prospective study was conducted in pediatric ward of Assam Medical College Hospital to evaluate the clinical profile and outcome of JE in ch...

  8. Blood antioxidant profile and lipid peroxides in dairy cows with clinical mastitis

    OpenAIRE

    Rajesh Rathore; Vinod Kumar Gupta; Ricky Jhambh; Umesh Dimri

    2013-01-01

    Aim: To evaluate blood antioxidant profile and lipid peroxides in dairy cows with clinical mastitis. Materials and Methods: Twelve cases of clinical mastitis in cross-bred cows were selected based on physical examination of udder and milk, California Mastitis Test (CMT), Somatic Cell Count (SCC) and confirmation by bacteriological examination of milk and requisite biochemical tests. Twelve lactating cows showing negative CMT reaction and SCC <2x105 cells/ml were considered as healthy contr...

  9. Clinical and molecular characterization of limb-girdle muscular dystrophy due to LAMA2 mutations

    DEFF Research Database (Denmark)

    Gavassini, Bruno F; Carboni, Nicola; Nielsen, Jørgen E;

    2011-01-01

    In this study we describe the clinical and molecular characteristics of limb-girdle muscular dystrophy (LGMD) due to LAMA2 mutations.......In this study we describe the clinical and molecular characteristics of limb-girdle muscular dystrophy (LGMD) due to LAMA2 mutations....

  10. Molecular Fixative Enables Expression Microarray Analysis of Microdissected Clinical Cervical Specimens

    OpenAIRE

    Li, Gerald; Van Niekerk, Dirk; Miller, Dianne; Ehlen, Thomas; Garnis, Cathie; Follen, Michele; Guillaud, Martial; MacAulay, Calum

    2014-01-01

    Formalin-fixed tissue has been a mainstay of clinical pathology laboratories, but formalin alters many biomolecules, including nucleic acids and proteins. Meanwhile, frozen tissues contain better-preserved biomolecules, but tissue morphology is affected, limiting their diagnostic utility. Molecular fixatives promise to bridge this gap by simultaneously preserving morphology and biomolecules, enabling clinical diagnosis and molecular analyses on the same specimen. While previ...

  11. Investigating the effects of chemistry on molecular line profiles of infalling low mass cores

    CERN Document Server

    Roberts, Julia F; Rawlings, Jonathan M C

    2010-01-01

    We have coupled a chemical model with two dynamical models of collapsing low mass star-forming cores to predict abundances across the core of the commonly used infall tracers, CS and HCO$^+$, at various stages of the collapse. The models investigated are a new ambipolar diffusion model and the `inside-out' collapse model. We have then used these results as an input to a radiative transfer model to predict the line profiles of several transitions of these molecules. For the inside-out collapse model, we predict significant molecular depletion due to freeze-out in the core centre, which prevents the formation of the blue asymmetry (believed to be the `signature' of infall) in the line profiles. Molecular depletion also occurs in the ambipolar diffusion model during the late stages of collapse, but the line profiles still exhibit a strong blue asymmetry due to extended infall. For the inside-out collapse model to exhibit the blue asymmetry it is necessary to impose a negative kinetic temperature gradient on the ...

  12. Molecular Characterization and Antimicrobial Sensitivity of Pathogens from Sub-Clinical and Clinical Mastitis in Eastern China

    OpenAIRE

    Javed Memon, Jam Kashif, Muhammad Yaqoob, Wang Liping, Yongchun Yang and Fan Hongjie*

    2013-01-01

    Prevalence of sub-clinical and clinical coliform mastitis with antimicrobial sensitivity profile of various mastitis-causing organisms was investigated. Milk samples collected from 299 cows infected with clinical mastitis to evaluate the prevalence of coliform mastitis and 1660 quarters milk samples randomly collected from 415 lactating cows for detection of subclinical mastitis (SCM) by Hangzhou Mastitis Test (HMT). SCM at quarters and cow level was recorded to be 20.2 and 52.3%, respectivel...

  13. Clinical and medication profiles stratified by household income in patients referred for diabetes care

    Directory of Open Access Journals (Sweden)

    Svenson Lawrence W

    2007-03-01

    Full Text Available Abstract Background Low income individuals with diabetes are at particularly high risk for poor health outcomes. While specialized diabetes care may help reduce this risk, it is not currently known whether there are significant clinical differences across income groups at the time of referral. The objective of this study is to determine if the clinical profiles and medication use of patients referred for diabetes care differ across income quintiles. Methods This cross-sectional study was conducted using a Canadian, urban, Diabetes Education Centre (DEC database. Clinical information on the 4687 patients referred to the DEC from May 2000 – January 2002 was examined. These data were merged with 2001 Canadian census data on income. Potential differences in continuous clinical parameters across income quintiles were examined using regression models. Differences in medication use were examined using Chi square analyses. Results Multivariate regression analysis indicated that income was negatively associated with BMI (p Conclusion Our findings demonstrate that low income patients present to diabetes clinic older, heavier and with a more atherogenic lipid profile than do high income patients. Overall medication use was higher among the lower income group suggesting that differences in clinical profiles are not the result of under-treatment, thus invoking lifestyle factors as potential contributors to these findings.

  14. Data on alteration of hormone and growth factor receptor profiles over progressive passages of breast cancer cell lines representing different clinical subtypes.

    Science.gov (United States)

    Nair, Madhumathy G; Desai, Krisha; Prabhu, Jyothi S; Hari, P S; Remacle, Jose; Sridhar, T S

    2016-09-01

    Human breast cancers are a highly heterogeneous group of tumours consisting of several molecular subtypes with a variable profile of hormone, growth factor receptors and cytokeratins [1]. Here, the data shows immunofluorescence profiling of four different cell lines belonging to distinct clinical subtypes of breast cancer. Post revival, the cell lines were passaged in culture and immunophenotyping was done for ER, HER-2, AR and EGFR. Data for the markers from early passage (5th) through passages as late as 25 for the different cell lines is presented. PMID:27508248

  15. Transcriptional profiling at whole population and single cell levels reveals somatosensory neuron molecular diversity.

    Science.gov (United States)

    Chiu, Isaac M; Barrett, Lee B; Williams, Erika K; Strochlic, David E; Lee, Seungkyu; Weyer, Andy D; Lou, Shan; Bryman, Gregory S; Roberson, David P; Ghasemlou, Nader; Piccoli, Cara; Ahat, Ezgi; Wang, Victor; Cobos, Enrique J; Stucky, Cheryl L; Ma, Qiufu; Liberles, Stephen D; Woolf, Clifford J

    2014-01-01

    The somatosensory nervous system is critical for the organism's ability to respond to mechanical, thermal, and nociceptive stimuli. Somatosensory neurons are functionally and anatomically diverse but their molecular profiles are not well-defined. Here, we used transcriptional profiling to analyze the detailed molecular signatures of dorsal root ganglion (DRG) sensory neurons. We used two mouse reporter lines and surface IB4 labeling to purify three major non-overlapping classes of neurons: 1) IB4(+)SNS-Cre/TdTomato(+), 2) IB4(-)SNS-Cre/TdTomato(+), and 3) Parv-Cre/TdTomato(+) cells, encompassing the majority of nociceptive, pruriceptive, and proprioceptive neurons. These neurons displayed distinct expression patterns of ion channels, transcription factors, and GPCRs. Highly parallel qRT-PCR analysis of 334 single neurons selected by membership of the three populations demonstrated further diversity, with unbiased clustering analysis identifying six distinct subgroups. These data significantly increase our knowledge of the molecular identities of known DRG populations and uncover potentially novel subsets, revealing the complexity and diversity of those neurons underlying somatosensation. PMID:25525749

  16. PIGE - Resonance profiling applied to a clinical test of flouride varnishes

    Science.gov (United States)

    Zschau, H. E.; Plier, F.; Otto, G.; Wyrwich, C.; Treide, A.

    1992-03-01

    A clinical in-vivo experiment had been carried out to compare two caries preventing fluorine varnishes. The fluorine depth profiles in the near surface region of tooth enamel were measured using the 935 keV resonance of the nuclear reaction 19F( p, p' γ) 19F. The results can be understood by studying the flourine anamnese of the patients.

  17. Protein Profile study of clinical samples using Laser Induced Fluorescence as the detection method

    DEFF Research Database (Denmark)

    Karemore, Gopal Raghunath; Raja, Sujatha N.; Rai, Lavanya;

    2009-01-01

    by using hard and Fuzzy clustering methods. The study was performed to test the utility of the HPLC-LIF protein profiling method for classification of tissue samples as well as to establish a complementary method for histopathology for clinical diagnosis of the tissue as normal or malignant.  ...

  18. A behavioral and cognitive profile of clinically stable HIV-infected children

    NARCIS (Netherlands)

    Nozyce, ML; Lee, SS; Wiznia, A; Nachman, S; Mofenson, LM; Smith, ME; Yogev, R; McIntosh, K; Stanley, K; Pelton, S

    2006-01-01

    OBJECTIVE. The purpose of this research was to characterize behavioral and cognitive profiles of clinically and immunologically stable antiretroviral-experienced HIV-infected children. METHODS. Two hundred seventy-four previously treated HIV-infected children aged 2 to 17 years were assessed for beh

  19. Head and neck paragangliomas: clinical and molecular genetic classification.

    Science.gov (United States)

    Offergeld, Christian; Brase, Christoph; Yaremchuk, Svetlana; Mader, Irina; Rischke, Hans Christian; Gläsker, Sven; Schmid, Kurt W; Wiech, Thorsten; Preuss, Simon F; Suárez, Carlos; Kopeć, Tomasz; Patocs, Attila; Wohllk, Nelson; Malekpour, Mahdi; Boedeker, Carsten C; Neumann, Hartmut P H

    2012-01-01

    Head and neck paragangliomas are tumors arising from specialized neural crest cells. Prominent locations are the carotid body along with the vagal, jugular, and tympanic glomus. Head and neck paragangliomas are slowly growing tumors, with some carotid body tumors being reported to exist for many years as a painless lateral mass on the neck. Symptoms depend on the specific locations. In contrast to paraganglial tumors of the adrenals, abdomen and thorax, head and neck paragangliomas seldom release catecholamines and are hence rarely vasoactive. Petrous bone, jugular, and tympanic head and neck paragangliomas may cause hearing loss. The internationally accepted clinical classifications for carotid body tumors are based on the Shamblin Class I-III stages, which correspond to postoperative permanent side effects. For petrous-bone paragangliomas in the head and neck, the Fisch classification is used. Regarding the molecular genetics, head and neck paragangliomas have been associated with nine susceptibility genes: NF1, RET, VHL, SDHA, SDHB, SDHC, SDHD, SDHAF2 (SDH5), and TMEM127. Hereditary HNPs are mostly caused by mutations of the SDHD gene, but SDHB and SDHC mutations are not uncommon in such patients. Head and neck paragangliomas are rarely associated with mutations of VHL, RET, or NF1. The research on SDHA, SDHAF2 and TMEM127 is ongoing. Multiple head and neck paragangliomas are common in patients with SDHD mutations, while malignant head and neck paraganglioma is mostly seen in patients with SDHB mutations. The treatment of choice is surgical resection. Good postoperative results can be expected in carotid body tumors of Shamblin Class I and II, whereas operations on other carotid body tumors and other head and neck paragangliomas frequently result in deficits of the cranial nerves adjacent to the tumors. Slow growth and the tendency of hereditary head and neck paragangliomas to be multifocal may justify less aggressive treatment strategies. PMID:22584701

  20. Head and neck paragangliomas: clinical and molecular genetic classification

    Directory of Open Access Journals (Sweden)

    Christian Offergeld

    2012-01-01

    Full Text Available Head and neck paragangliomas are tumors arising from specialized neural crest cells. Prominent locations are the carotid body along with the vagal, jugular, and tympanic glomus. Head and neck paragangliomas are slowly growing tumors, with some carotid body tumors being reported to exist for many years as a painless lateral mass on the neck. Symptoms depend on the specific locations. In contrast to paraganglial tumors of the adrenals, abdomen and thorax, head and neck paragangliomas seldom release catecholamines and are hence rarely vasoactive. Petrous bone, jugular, and tympanic head and neck paragangliomas may cause hearing loss. The internationally accepted clinical classifications for carotid body tumors are based on the Shamblin Class I-III stages, which correspond to postoperative permanent side effects. For petrous-bone paragangliomas in the head and neck, the Fisch classification is used. Regarding the molecular genetics, head and neck paragangliomas have been associated with nine susceptibility genes: NF1, RET, VHL, SDHA, SDHB, SDHC, SDHD, SDHAF2 (SDH5, and TMEM127. Hereditary HNPs are mostly caused by mutations of the SDHD gene, but SDHB and SDHC mutations are not uncommon in such patients. Head and neck paragangliomas are rarely associated with mutations of VHL, RET, or NF1. The research on SDHA, SDHAF2 and TMEM127 is ongoing. Multiple head and neck paragangliomas are common in patients with SDHD mutations, while malignant head and neck paraganglioma is mostly seen in patients with SDHB mutations. The treatment of choice is surgical resection. Good postoperative results can be expected in carotid body tumors of Shamblin Class I and II, whereas operations on other carotid body tumors and other head and neck paragangliomas frequently result in deficits of the cranial nerves adjacent to the tumors. Slow growth and the tendency of hereditary head and neck paragangliomas to be multifocal may justify less aggressive treatment strategies.

  1. Nontypable Haemophilus influenzae displays a prevalent surface structure molecular pattern in clinical isolates.

    Directory of Open Access Journals (Sweden)

    Pau Martí-Lliteras

    Full Text Available Non-typable Haemophilus influenzae (NTHi is a gram negative pathogen that causes acute respiratory infections and is associated with the progression of chronic respiratory diseases. Previous studies have established the existence of a remarkable genetic variability among NTHi strains. In this study we show that, in spite of a high level of genetic heterogeneity, NTHi clinical isolates display a prevalent molecular feature, which could confer fitness during infectious processes. A total of 111 non-isogenic NTHi strains from an identical number of patients, isolated in two distinct geographical locations in the same period of time, were used to analyse nine genes encoding bacterial surface molecules, and revealed the existence of one highly prevalent molecular pattern (lgtF+, lic2A+, lic1D+, lic3A+, lic3B+, siaA-, lic2C+, ompP5+, oapA+ displayed by 94.6% of isolates. Such a genetic profile was associated with a higher bacterial resistance to serum mediated killing and enhanced adherence to human respiratory epithelial cells.

  2. Nontypable Haemophilus influenzae Displays a Prevalent Surface Structure Molecular Pattern in Clinical Isolates

    Science.gov (United States)

    Mauro, Silvia; Hood, Derek W.; Viadas, Cristina; Calatayud, Laura; Morey, Pau; Servin, Alain; Liñares, Josefina; Oliver, Antonio; Bengoechea, José Antonio; Garmendia, Junkal

    2011-01-01

    Non-typable Haemophilus influenzae (NTHi) is a Gram negative pathogen that causes acute respiratory infections and is associated with the progression of chronic respiratory diseases. Previous studies have established the existence of a remarkable genetic variability among NTHi strains. In this study we show that, in spite of a high level of genetic heterogeneity, NTHi clinical isolates display a prevalent molecular feature, which could confer fitness during infectious processes. A total of 111 non-isogenic NTHi strains from an identical number of patients, isolated in two distinct geographical locations in the same period of time, were used to analyse nine genes encoding bacterial surface molecules, and revealed the existence of one highly prevalent molecular pattern (lgtF+, lic2A+, lic1D+, lic3A+, lic3B+, siaA−, lic2C+, ompP5+, oapA+) displayed by 94.6% of isolates. Such a genetic profile was associated with a higher bacterial resistance to serum mediated killing and enhanced adherence to human respiratory epithelial cells. PMID:21698169

  3. P-Cygni Profiles of Molecular Lines toward Arp 220 Nuclei

    CERN Document Server

    Sakamoto, Kazushi; Wilner, David J; Black, John H; Conway, John E; Costagliola, Francesco; Peck, Alison B; Spaans, Marco; Wang, Junzhi; Wiedner, Martina C

    2009-01-01

    We report ~100 pc (0.3") resolution observations of (sub)millimeter HCO+ and CO lines in the ultraluminous infrared galaxy Arp 220. The lines peak at two merger nuclei, with HCO+ being more spatially concentrated than CO. Asymmetric line profiles with blueshifted absorption and redshifted emission are discovered in HCO+(3-2) and (4-3) toward the two nuclei and in CO(3-2) toward one nucleus. We suggest that these P-Cygni profiles are due to ~100 km/s outward motion of molecular gas from the nuclei. This gas is most likely outflowing from the inner regions of the two nuclear disks rotating around individual nuclei, clearing the shroud around the luminosity sources there.

  4. Genetic profiling of the Plasmodium falciparum population using antigenic molecular markers.

    Science.gov (United States)

    Gupta, Purva; Singh, Ruchi; Khan, Haris; Raza, Adil; Yadavendu, Veena; Bhatt, R M; Singh, Vineeta

    2014-01-01

    About 50% of malaria infections in India are attributed to Plasmodium falciparum but relatively little is known about the genetic structure of the parasite populations. The molecular genotyping of the parasite populations by merozoite surface protein (msp1 and msp2) and glutamate-rich protein (glurp) genes identifies the existing parasite population in the regions which help in understanding the molecular mechanisms involved in the parasite's drive for survival. This study reveals the genetic profile of the parasite population in selected regions across the country with varying degree of endemicity among them. We also report the prevalence of Pfcrt mutations in this parasite population to evaluate the pattern of drug resistance development in them. PMID:25405214

  5. APRIL is a novel clinical chemo-resistance biomarker in colorectal adenocarcinoma identified by gene expression profiling

    International Nuclear Information System (INIS)

    5-Fluorouracil(5FU) and oral analogues, such as capecitabine, remain one of the most useful agents for the treatment of colorectal adenocarcinoma. Low toxicity and convenience of administration facilitate use, however clinical resistance is a major limitation. Investigation has failed to fully explain the molecular mechanisms of resistance and no clinically useful predictive biomarkers for 5FU resistance have been identified. We investigated the molecular mechanisms of clinical 5FU resistance in colorectal adenocarcinoma patients in a prospective biomarker discovery project utilising gene expression profiling. The aim was to identify novel 5FU resistance mechanisms and qualify these as candidate biomarkers and therapeutic targets. Putative treatment specific gene expression changes were identified in a transcriptomics study of rectal adenocarcinomas, biopsied and profiled before and after pre-operative short-course radiotherapy or 5FU based chemo-radiotherapy, using microarrays. Tumour from untreated controls at diagnosis and resection identified treatment-independent gene expression changes. Candidate 5FU chemo-resistant genes were identified by comparison of gene expression data sets from these clinical specimens with gene expression signatures from our previous studies of colorectal cancer cell lines, where parental and daughter lines resistant to 5FU were compared. A colorectal adenocarcinoma tissue microarray (n = 234, resected tumours) was used as an independent set to qualify candidates thus identified. APRIL/TNFSF13 mRNA was significantly upregulated following 5FU based concurrent chemo-radiotherapy and in 5FU resistant colorectal adenocarcinoma cell lines but not in radiotherapy alone treated colorectal adenocarcinomas. Consistent withAPRIL's known function as an autocrine or paracrine secreted molecule, stromal but not tumour cell protein expression by immunohistochemistry was correlated with poor prognosis (p = 0.019) in the independent set

  6. Considerations for clinical read alignment and mutational profiling using next-generation sequencing

    Directory of Open Access Journals (Sweden)

    Gavin R Oliver

    2012-07-01

    Full Text Available Next-generation sequencing technologies are increasingly being applied in clinical settings, however the data are characterized by a range of platform-specific artifacts making downstream analysis problematic and error prone. One major application of NGS is in the profiling of clinically relevant mutations whereby sequences are aligned to a reference genome and potential mutations assessed and scored. Accurate sequence alignment is pivotal in reliable assessment of potential mutations however selection of appropriate alignment tools is a non-trivial task complicated by the availability of multiple solutions each with its own performance characteristics. Using BRCA1 as an example, we have simulated and mutated a test dataset based on Illumina sequencing technology. Our findings reveal key differences in the performances of a range of common commercial and open source tools and will be of importance to anyone using NGS to profile mutations in clinical or basic research.

  7. Reproducibility of mass spectrometry based protein profiles for diagnosis of ovarian cancer across clinical studies

    DEFF Research Database (Denmark)

    Øgendahl Callesen, Anne Kjærgaard; Mogensen, Ole; Jensen, Andreas K;

    2012-01-01

    The focus of this systematic review is to give an overview of the current status of clinical protein profiling studies using MALDI and SELDI MS platforms in the search for ovarian cancer biomarkers. A total of 34 profiling studies were qualified for inclusion in the review. Comparative analysis......, and data analysis. About 47% of the peaks reported to be associated to ovarian cancer were also represented in our experimental study, and 34% of these redetected peaks also showed a significant difference between cases and controls in our study. Thus, despite known problems related to reproducibility...... an overlap in peaks between clinical studies was demonstrated, which indicate convergence toward a set of common discriminating, reproducible peaks for ovarian cancer. The potential of the discriminating protein peaks for clinical use as ovarian cancer biomarkers will be discussed and evaluated. This article...

  8. Epidemiological and clinical profile of triple negative breast cancer at a cancer hospital in North India

    Directory of Open Access Journals (Sweden)

    P Suresh

    2013-01-01

    Full Text Available Background: Triple negative breast cancer (TNBC is a recent concept and the burning topic of research today. Various studies have been reported in western literature on TNBCs or the similar group of basal like cancers, all highlighting the poor prognostic features of this molecular subtype in comparison to the other types of breast cancers. However extensive data from India is lacking. The aim of this study was to analyze the epidemiological and clinical profile of TNBcs at our institute. Materials and Methods: Data on 171 patients of TNBCs registered at this hospital between 2005 and 2008 and followed up until December 2010 was collected and reviewed for epidemiological and clinical features. Results: The median age at presentation was 49 years (22-75 years. Sixty eight patients (40% had lump in the breast of less than 1 month duration. Fourteen (8% were nulliparous and 10 (7% patients had crossed the age of 30 years at first full-term pregnancy, 89 (52% were pre or peri-menopausal at presentation. Only 8 (5% patients had a family history of breast or ovarian cancer. One hundred and six (62% patients were stage II, 26 (15% stage III, 21 (12% stage I and 18 (10% stage IV at presentation. One hundred and twenty eight patients (75% had early breast cancer eligible for surgery at presentation, 25 (15% were locally advanced and received neoadjuvant chemotherapy (NACT and 18 (10% were found to be metastatic. Modified radical mastectomy was the preferred surgical option by most patients (76% who underwent upfront surgery in our study. The pathological overall response rates (complete and partial response after NACT was 75% with complete response rate of 25% and there were no relapses in the complete responders. The median follow-up was 30 months (9-70 months. One hundred and twenty two patients (71% were alive at last follow-up, 34 (22% had relapsed, 18 (11% had died due to progressive disease. Thirty one patients (18% were lost to follow-up. Most of

  9. Concept and approach of human signal-molecular-profiling database: a pilot study on depression using Lab-on-chips.

    Science.gov (United States)

    Dong, Tao; Zhao, Xinyan; Yang, Zhaochu

    2013-01-01

    Signal molecular profiling (SMP) in serum can reveal abundant medical information about the human body. The construction of a human signal-molecular-profiling database (HSMPD) will greatly prompt the research of medical science. However, some challenges hinder the construction of HSMPD. A promising strategy is proposed to provide a convenient way for the establishment of HSMPD. Firstly, a low-cost and high-throughput tool for measuring SMP should be developed and standardized. When the SMP-oriented tools were accepted by most hospitals worldwide, SMP information will be decoded by a cloud-based system and stored into the online database naturally. In the pilot study, an ultrasensitive Lab-on-chips (LOC) device was developed as a specific tool for SMP. Clinical serum samples from 10 women within 4 weeks of giving birth, including 2 patients with postpartum depression were studied by the LOC devices, since accumulating evidence has indicated that hormones and cytokines in patients with mood disorders are abnormal. HSMPD may be applied to diagnose depression in the future. Here, five kinds of signal molecules were quantified on the devices, namely, tumor necrosis factor-alpha (TNF-α), thyroid-stimulating hormone (TSH), interleukin (IL)-2, IL-6 and IL-8. The preliminary results showed that the concentrations of IL-2 and IL-8 in the depression group may be higher than those in the control group, whereas the other kinds of signal molecules did not change significantly. Although the correlations are not enough to induct any diagnostic criterion, the SMP-oriented tool was verified. The results also indicated that the strategy to establish HSMPD is conceivable.

  10. Chronic myelogenous leukemia: molecular monitoring in clinical practice

    Directory of Open Access Journals (Sweden)

    N. R. Ryabchikova

    2013-01-01

    Full Text Available Use of tyrosine kinase inhibitor imatinib has led to significant progress in chronic myeloid leukemia (CML treatment. To date, genetic monitoring is a mandatory attribute of therapy with tyrosine kinase inhibitors. The purpose of this study was to access the imatinib therapy efficacy in CML patients using complete molecular genetic monitoring by standard cytogenetics, realtime polymerase chain reaction and mutational analysis. Correlation between cytogenetic and molecular response was shown. Heterogeneity of molecular response in each patient group was revealed by expression of BCR-ABL. Kinase domain mutations were detected in 32 % of CML patients resistant to imatinib.

  11. Total Protein Profile and Drug Resistance in Candida albicans Isolated from Clinical Samples

    Directory of Open Access Journals (Sweden)

    Kamal Uddin Zaidi

    2016-01-01

    Full Text Available This study was done to assess the antifungal susceptibility of clinical isolates of Candida albicans and to evaluate its total protein profile based on morphological difference on drug resistance. Hundred and twenty clinical isolates of C. albicans from various clinical specimens were tested for susceptibility against four antifungal agents, namely, fluconazole, itraconazole, amphotericin B, and ketoconazole. A significant increase of drug resistance in clinical isolates of C. albicans was observed. The study showed 50% fluconazole and itraconazole resistance at 32 μg mL−1 with a MIC50 and MIC90 values at 34 and 47 and 36 and 49 μg mL−1, respectively. All isolates were sensitive to amphotericin B and ketoconazole. The SDS-PAGE protein profile showed a prevalent band of ~52.5 kDa, indicating overexpression of gene in 72% strains with fluconazole resistance. Since the opportunistic infections of Candida spp. are increasing along with drug resistance, the total protein profile will help in understanding the evolutionary changes in drug resistance and also to characterize them.

  12. Prediction consistency and clinical presentations of breast cancer molecular subtypes for Han Chinese population

    Directory of Open Access Journals (Sweden)

    Huang Chi-Cheng

    2012-09-01

    Full Text Available Abstract Background Breast cancer is a heterogeneous disease in terms of transcriptional aberrations; moreover, microarray gene expression profiles had defined 5 molecular subtypes based on certain intrinsic genes. This study aimed to evaluate the prediction consistency of breast cancer molecular subtypes from 3 distinct intrinsic gene sets (Sørlie 500, Hu 306 and PAM50 as well as clinical presentations of each molecualr subtype in Han Chinese population. Methods In all, 169 breast cancer samples (44 from Taiwan and 125 from China of Han Chinese population were gathered, and the gene expression features corresponding to 3 distinct intrinsic gene sets (Sørlie 500, Hu 306 and PAM50 were retrieved for molecular subtype prediction. Results For Sørlie 500 and Hu 306 intrinsic gene set, mean-centring of genes and distance-weighted discrimination (DWD remarkably reduced the number of unclassified cases. Regarding pairwise agreement, the highest predictive consistency was found between Hu 306 and PAM50. In all, 150 and 126 samples were assigned into identical subtypes by both Hu 306 and PAM50 genes, under mean-centring and DWD. Luminal B tended to show a higher nuclear grade and have more HER2 over-expression status than luminal A did. No basal-like breast tumours were ER positive, and most HER2-enriched breast tumours showed HER2 over-expression, whereas, only two-thirds of ER negativity/HER2 over-expression tumros were predicted as HER2-enriched molecular subtype. For 44 Taiwanese breast cancers with survival data, a better prognosis of luminal A than luminal B subtype in ER-postive breast cancers and a better prognosis of basal-like than HER2-enriched subtype in ER-negative breast cancers was observed. Conclusions We suggest that the intrinsic signature Hu 306 or PAM50 be used for breast cancers in the Han Chinese population during molecular subtyping. For the prognostic value and decision making based on intrinsic subtypes, further prospective

  13. Hamartomatous polyps - a clinical and molecular genetic study.

    Science.gov (United States)

    Jelsig, Anne Marie

    2016-08-01

    Hamartomatous polyps (HPs) in the gastrointestinal (GI) tract are rare compared to other types of GI polyps, yet they are the most common type of polyp in children. The symptoms are usually rectal bleeding, abdominal pain, obstipation, anaemia, and/or small bowel obstruction. The polyps are typically removed concurrently with endoscopy when located in the colon, rectum, or stomach, whereas polyps in the small bowel are removed during push-enteroscopy, device-assisted enteroscopy, or by surgery. HPs can be classified as juvenile polyps or Peutz-Jeghers polyps based on their histopathological appearance. Patients with one or a few juvenile polyps are usually not offered clinical follow-up as the polyp(s) are considered not to harbour any malignant potential. Nevertheless, it is important to note that juvenile polyps and HPs are also found in patients with hereditary hamartomatous polyposis syndromes (HPS). Patients with HPS have an increased risk of cancer, recurrences of polyps, and extraintestinal complications. The syndromes are important to diagnose, as patients should be offered surveillance from childhood or early adolescence. The syndromes include juvenile polyposis syndrome, Peutz-Jeghers syndrome, and the PTEN hamartoma tumour syndrome. Currently, the HPS diagnoses are based on clinical criteria and are often assisted with genetic testing as candidate genes have been described for each syndrome. This thesis is based on six scientific papers. The overall aim of the studies was to expand the knowledge on clinical course and molecular genetics in patients with HPs and HPS, and to investigate research participants' attitude towards the results of extensive genetic testing.   Paper I: In the first paper we investigated the occurrence, anatomic distribution, and other demographics of juvenile polyps in the colon and rectum in Denmark in 1995-2014. Based on the Danish Pathology Data Bank we found that 1772 patients had 2108 JPs examined in the period, and we

  14. Molecular risk assessment of BIG 1-98 participants by expression profiling using RNA from archival tissue

    Directory of Open Access Journals (Sweden)

    Giobbie-Hurder Anita

    2010-02-01

    Full Text Available Abstract Background The purpose of the work reported here is to test reliable molecular profiles using routinely processed formalin-fixed paraffin-embedded (FFPE tissues from participants of the clinical trial BIG 1-98 with a median follow-up of 60 months. Methods RNA from fresh frozen (FF and FFPE tumor samples of 82 patients were used for quality control, and independent FFPE tissues of 342 postmenopausal participants of BIG 1-98 with ER-positive cancer were analyzed by measuring prospectively selected genes and computing scores representing the functions of the estrogen receptor (eight genes, ER_8, the progesterone receptor (five genes, PGR_5, Her2 (two genes, HER2_2, and proliferation (ten genes, PRO_10 by quantitative reverse transcription PCR (qRT-PCR on TaqMan Low Density Arrays. Molecular scores were computed for each category and ER_8, PGR_5, HER2_2, and PRO_10 scores were combined into a RISK_25 score. Results Pearson correlation coefficients between FF- and FFPE-derived scores were at least 0.94 and high concordance was observed between molecular scores and immunohistochemical data. The HER2_2, PGR_5, PRO_10 and RISK_25 scores were significant predictors of disease free-survival (DFS in univariate Cox proportional hazard regression. PRO_10 and RISK_25 scores predicted DFS in patients with histological grade II breast cancer and in lymph node positive disease. The PRO_10 and PGR_5 scores were independent predictors of DFS in multivariate Cox regression models incorporating clinical risk indicators; PRO_10 outperformed Ki-67 labeling index in multivariate Cox proportional hazard analyses. Conclusions Scores representing the endocrine responsiveness and proliferation status of breast cancers were developed from gene expression analyses based on RNA derived from FFPE tissues. The validation of the molecular scores with tumor samples of participants of the BIG 1-98 trial demonstrates that such scores can serve as independent prognostic

  15. Clinical and molecular studies on differentiated thyroid carcinoma management

    NARCIS (Netherlands)

    Abdulrahman Hareedy, Randa Mostafa

    2015-01-01

    This thesis describes clinical and fundamental studies addressing clinical challenges in patients with differentiated thyroid carcinoma (DTC). The diagnosis of DTC is hampered by the fact that although the incidence is low thyroid nodules are prevalent. In this thesis, the diagnostic value of a pote

  16. Clinical and psychosocial profile of HIV orphans in Northern Karnataka – a longitudinal study

    Directory of Open Access Journals (Sweden)

    Mahesh.V

    2013-07-01

    Full Text Available Background India currently has an estimated 220,000 children infected by HIV/AIDS and is home to the largest number of AIDS Orphans only next to South Africa in the world. The pandemic not only deprives Orphans of their rights to enjoy a good or a normal childhood, but it also has deleterious effects on their chances of survival or well-being. Thus the future of these children orphaned by the AIDS epidemic addresses a key social issue. Hence this study was done with the objectives, to assess the Demographic profile, Clinical profile and psycho-social profile of HIV Orphans. Methods A Longitudinal study on 82 HIV orphans in the age group 5 to 15yrs was conducted after obtaining informed consent from their caregivers for duration of one year from at Anti retroviral therapy (ART centre KIMS, Hubli. Clinical profile was assessed by WHO staging of HIV, Child Behavior Checklist (CBCL was used to assess Psycho-Social Profile. Chi-square test, paired t test are the tests of significance for qualitative and quantitative variables respectively. Results Mother to Child was the most common mode of transmission in majority of cases i.e 97%. Among the orphans 60% of them were deprived of mother’s care i.e Double orphans and maternal orphans. Majority of subjects i.e 29 (35.4% were in stage 2 of WHO clinical staging. 27(32.9% were in mild immunosuppression at 350 to 499 Absolute lymphocytic count and CD4% in the range of 20 to 25% in 26(31.7%. A statistically significant increase of psychosocial problem in orphans was observed during the follow-up. Conclusion It can be concluded that during the follow-up Psycho-social problems increased in Orphans significantly.

  17. Clinical Pharmacology of Alpha-1 Blockers Improving Drug-profile through Novel Formulations.

    Science.gov (United States)

    Nerurkar, Rajan P; Ved, Jignesh K

    2014-09-01

    Clinical pharmacology is an essential consideration in chronic therapies, and may play a significant role in modifying the pharmacological characteristics of drug formulations. Improvement in drug formulations may ensure their safe and effective use over a period of time. This has been particularly observed with α-1 adrenergic blockers in hypertension management. Advancements in formulations like prazosin GITS, have resulted in improvement in tolerability profile and smoother, more effective blood pressure control, which reasonably translate into improvement in patient compliance and better clinical outcomes.

  18. Dengue infection in children and adolescents: Clinical profile in a reference hospital in northeast Brazil

    Directory of Open Access Journals (Sweden)

    Roberto da Justa Pires Neto

    2013-12-01

    Full Text Available Introduction This study aimed to describe the clinical spectrum of dengue in children and adolescents from a hyperendemic region who were admitted for hospitalization. Methods A retrospective study was conducted on patients diagnosed with dengue infection upon admission to a reference center in Fortaleza, Brazil. Results Of the 84 patients included, 42 underwent confirmatory testing. The main symptoms were fever, abdominal pain and vomiting. The median level of serum aspartate aminotransferase was 143.5±128mg/dL. Conclusions A peculiar clinical profile was evident among children and adolescents with dengue infection in a reference center in northeast Brazil, including gastrointestinal symptoms and liver involvement.

  19. Prevalence and clinical profile of diabetes mellitus in productive aged urban Indonesians

    OpenAIRE

    Mihardja, Laurentia; Soetrisno, Uken; Soegondo, Sidartawan

    2013-01-01

    Abstract Aims/Introduction To estimate the prevalence and clinical profile of diabetes mellitus in productive aged urban Indonesians based on the National Basic Health Research 2007. Materials and Methods The statistical analyses of a cross‐sectional survey included the data of 15,332 adults, aged 18–55 years, living in an urban area. Blood glucose was measured by an automatic clinical chemistry analyzer by 2‐h, 75‐g post glucose load after an overnight fast. Weight, height, waist circumferen...

  20. Immunohistochemical profile of laryngeal cancers with different clinical course and efficiency of treatment.

    OpenAIRE

    Shponka I.S.; Gritsenko P.A.; Kovtunenko A.V.

    2007-01-01

    The cancer of larynx is one of the most significant medical problems because of its high prevalence, high mortality and low survival rate. The retrospective analysis of specimens of 187 patients suffering from laryngeal squamous cell carcinoma of stage III-IV was performed. The purpose of our study was to substantiate the appropriateness of assessment of immunomorphological profile in estimation of biological behaviour of laryngeal cancer for prediction its clinical course and choice of opt...

  1. The distinct clinical profile of chronically critically ill patients: a cohort study

    OpenAIRE

    Estenssoro, Elisa; Reina, Rosa; Canales, Héctor S; Saenz, María Gabriela; Gonzalez, Francisco E; Aprea, María M; Laffaire, Enrique; Gola, Victor; Dubin, Arnaldo

    2006-01-01

    Introduction Our goal was to describe the epidemiology, clinical profiles, outcomes, and factors that might predict progression of critically ill patients to chronically critically ill (CCI) patients, a still poorly characterized subgroup. Methods We prospectively studied all patients admitted to a university-affiliated hospital intensive care unit (ICU) between 1 July 2002 and 30 June 2005. On admission, we recorded epidemiological data, the presence of organ failure (multiorgan dysfunction ...

  2. Characterization of Rheumatoid Arthritis Subtypes Using Symptom Profiles, Clinical Chemistry and Metabolomics Measurements

    OpenAIRE

    van Wietmarschen, Herman A.; Weidong Dai; van der Kooij, Anita J.; Theo H Reijmers; Yan Schroën; Mei Wang; Zhiliang Xu; Xinchang Wang; Hongwei Kong; Guowang Xu; Thomas Hankemeier; Meulman, Jacqueline J.; Jan van der Greef

    2012-01-01

    Objective: The aim is to characterize subgroups or phenotypes of rheumatoid arthritis (RA) patients using a systems biology approach. The discovery of subtypes of rheumatoid arthritis patients is an essential research area for the improvement of response to therapy and the development of personalized medicine strategies. Methods: In this study, 39 RA patients are phenotyped using clinical chemistry measurements, urine and plasma metabolomics analysis and symptom profiles. In addition, a Chine...

  3. A prospective study of reversible dementias: Frequency, causes, clinical profile and results of treatment

    OpenAIRE

    Srikanth S; Nagaraja A

    2005-01-01

    Background: Dementia due to potentially reversible etiologies is an important group of dementias to be identified not only because of the number of such Patients encountered but also due to the potential for substantial improvement with treatment. Aims : To prospectively investigate the frequency and causes of dementias with potentially reversible etiologies; to examine the clinical features of this subgroup with a view to identifying a signature profile and to determine if this potential r...

  4. A STUDY ON CLINICAL, LABORATORY PROFILE AND OUTCOME OF DENGUE FEVER

    OpenAIRE

    Vanamali; Venugopal; Yeshwanth; Dilip

    2013-01-01

    ABSTRACT: BACKGROUND AND OBJECTIVES : In recent days there is an alarming increase in the incidence of dengue fever and has emerged as a serious international public health threat with almost half of the world's population at risk for infection . Very few studies have been conducted in this part of our country and hence this study was undertaken to study the clinical picture, la boratory profile and outcome of dengue fever in and around khammam. MATERIAL...

  5. THE STUDY OF PREVALENCE AND CLINICAL PROFILE OF VALVULAR HEART DISEASES IN A TEACHING HOSPITAL

    OpenAIRE

    Radha Krishnan; Srinivas

    2015-01-01

    Valvular heart disease is still a common causes of mortality and morbidity in India and rheumatic heart disease is still far more frequent. AIMS AND OBJECTIVES: To study the prevalence and clinical profile of rheumatic and non - rheumatic valvular heart dise ase in patients attending to Government General Hospital, Kakinada. MATERIALS AND METHODS: 100 Adult patients with valvular abnormalities attending to the Medicine and Cardiol...

  6. Profile of pregnancy in adolescence and related clinical-obstetric occurrences

    OpenAIRE

    Maria Veraci Oliveira Queiroz; Eysler Gonçalves Maia Brasil; Caroline Magalhães de Alcântara; Maria da Glória Oliveira Carneiro

    2014-01-01

    The objective was to characterize the profile of adolescence pregnancy and its clinical and obstetric events. Descriptive, cross-sectional study, with quantitative approach, developed in a tertiary hospital in Fortaleza, CE, Brazil, with one hundred adolescent mothers, through interviews and registers from the medical records, from February to May, 2011. Data were analyzed by Statistical Package for the Social Science software, version 17.0. The majority lived with a partner who earned up to ...

  7. Molecular Biology of Pancreatic Cancer: How Useful Is It in Clinical Practice?

    Directory of Open Access Journals (Sweden)

    George H Sakorafas

    2012-07-01

    Full Text Available Context During the recent two decades dramatic advances of molecular biology allowed an in-depth understanding of pancreatic carcinogenesis. It is currently accepted that pancreatic cancer has a genetic component. The real challenge is now how these impressive advances could be used in clinical practice. Objective To critically present currently available data regarding clinical application of molecular biology in pancreatic cancer. Methods Reports about clinical implications of molecular biology in patients with pancreatic cancer were retrieved from PubMed. These reports were selected on the basis of their clinical relevance, and the data of their publication (preferentially within the last 5 years. Emphasis was placed on reports investigating diagnostic, prognostic, and therapeutic implications. Results Molecular biology can be used to identify individuals at high-risk for pancreatic cancer development. Intensive surveillance is indicated in these patients to detect pancreatic neoplasia ideally at a preinvasive stage, when curative resection is still possible. Molecular biology can also be used in the diagnosis of pancreatic cancer, with molecular analysis on samples of biologic material, such as serum or plasma, duodenal fluid or preferentially pure pancreatic juice, pancreatic cells or tissue, and stools. Molecular indices have also prognostic significance. Finally, molecular biology may have therapeutic implications by using various therapeutic approaches, such as antiangiogenic factors, purine synthesis inhibitors, matrix metalloproteinase inhibitors, factors modulating tumor-stroma interaction, inactivation of the hedgehog pathway, gene therapy, oncolytic viral therapy, immunotherapy (both passive as well as active etc. Conclusion Molecular biology may have important clinical implications in patients with pancreatic cancer and represents one of the most active areas on cancer research. Hopefully clinical applications of molecular biology

  8. Molecular Portrait of Oral Tongue Squamous Cell Carcinoma Shown by Integrative Meta-Analysis of Expression Profiles with Validations

    Science.gov (United States)

    Thangaraj, Soundara Viveka; Shyamsundar, Vidyarani; Krishnamurthy, Arvind; Ramani, Pratibha; Ganesan, Kumaresan; Muthuswami, Muthulakshmi

    2016-01-01

    Oral Tongue Squamous cell carcinoma (OTSCC), the most frequently affected oral cancer sub-site, is associated with a poor therapeutic outcome and survival despite aggressive multi- modality management. Till date, there are no established biomarkers to indicate prognosis and outcome in patients presenting with tongue cancer. There is an urgent need for reliable molecular prognostic factors to enable identification of patients with high risk of recurrence and treatment failure in OTSCC management. In the current study, we present the meta-analysis of OTSCC microarray based gene expression profiles, deriving a comprehensive molecular portrait of tongue cancer biology, showing the relevant genes and pathways which can be pursued further to derive novel, tailored therapeutics as well as for prognostication. We have studied 5 gene expression profiling data sets available on exclusively oral tongue subsite comprising of sample size; n = 190, consisting of 111 tumors and 79 normals. The meta- analysis results showed 2405 genes differentially regulated comparing OTSCC tumor and normal. The top up regulated genes were found to be involved in Extracellular matrix degradation (ECM) and Epithelial to mesenchymal transition (EMT) pathways. The top down regulated genes were found to be involved in detoxication pathways. We validated the results in clinical samples (n = 206), comprising of histologically normals (n = 10), prospective (n = 29) and retrospective (n = 167) OTSCC by evaluating MMP9 and E-cadherin gene expression by qPCR and immunohistochemistry. Consistent with meta-analysis results, MMP9 mRNA expression was significantly up regulated in OTSCC primary tumors compared to normals. MMP9 protein over expression was found to be a significant predictor of poor prognosis, disease recurrence and poor Disease Free Survival (DFS) in OTSCC patients. Analysis by univariate and multivariate Cox proportional hazard model showed patients with loss of E-cadherin expression in OTSCC

  9. PET/SPECT molecular imaging in clinical neuroscience: recent advances in the investigation of CNS diseases

    OpenAIRE

    Lu, Feng-Mei; Yuan, Zhen

    2015-01-01

    Molecular imaging is an attractive technology widely used in clinical practice that greatly enhances our understanding of the pathophysiology and treatment in central nervous system (CNS) diseases. It is a novel multidisciplinary technique that can be defined as real-time visualization, in vivo characterization and qualification of biological processes at the molecular and cellular level. It involves the imaging modalities and the corresponding imaging agents. Nowadays, molecular imaging in n...

  10. CLINICAL PROFILE OF ACUTE LOWER RESPIRATORY TRACT INFECTIONS IN CHILDREN BETWEEN 2MONTHS TO 5 YEARS

    Directory of Open Access Journals (Sweden)

    Amitoj Singh Chhina

    2015-08-01

    Full Text Available BACKGROUND : Acute respiratory infections are a leading cause of morbidity and mortality in under - five children in developing countries. Hence, the present study was undertaken to study the various risk factors, clinical profile and outcome of acute lower respiratory tract infections (ALRI in children aged 2 month to 5 years. OBJECTIVE : clinical features, laborato ry assessment and morbidity and mortality pattern associated with acute lower respiratory tract infections in children aged 2 months to 5 years. METHODS: 100 ALRI cases fulfilling WHO criteria for pneumonia, in the age group of 2 month to 5 years were evaluated for clinical profile as per a predesigned proforma in a rural medical college. RESULTS : Of cases 61% were infants and remaining 39%12 - 60 months age group, males outnumbered females with sex ratio of 1.3;1. Elevated total leukocyte counts for age were observed in only 22% of cases, of these 3% were having pneumonia, 9% severe pneumonia and 10% very severe pneumonia. Significant association was found between leukocytosis and ALRI severity (p= 0.0001 Positive blood culture was obtained in 8% of cases and was significantly associated with ALRI severity (p=. 0.027. Among the ALRI cases, 84% required oxygen supplementation at any time during the hospital stay and 8% required mechanical ventilation. The mortality rate was 1%; with 99% of cases recovering and getting discharged uneventfully. CONCLUSION : Among the clinical variables, the signs and symptoms of ALRI as per the WHO ARI Control Programme were found in almost all cases. Regarding the laboratory profile, leukocytosis and blood culture positivity w ere observed in a small percentage, but significant association with ALRI severity was observed for both. Thus, clinical signs, and not invasive blood tests are a better diagnostic tools, though the latter may provide additional therapeutic and prognostic information in severe disease

  11. Characterization of molecular subtypes of Korean breast cancer: An ethnically and clinically distinct population

    OpenAIRE

    Han, Wonshik; Nicolau, Monica; Noh, Dong-Young; Jeffrey, Stefanie S.

    2010-01-01

    We aimed to investigate the molecular characteristics of Korean breast cancer. A cDNA microarray study (>42k clones) was performed on 69 breast cancers and three normal breast tissues. The subjects had a high percentage of HER-2 expression, hormone receptor negativity, and young onset. Molecular subtypes according to gene expression profiles were determined and their correlations to the clinicopathologic characteristics and patients outcome were analyzed. The tumors were subdivided into lumin...

  12. Angelman syndrome: review of clinical and molecular aspects

    OpenAIRE

    Bird LM

    2014-01-01

    Lynne M Bird1Department of Pediatrics, University of California, Division of Genetics, Rady Children’s Hospital, San Diego, California, USAAbstract: “Angelman syndrome” (AS) is a neurodevelopmental disorder whose main features are intellectual disability, lack of speech, seizures, and a characteristic behavioral profile. The behavioral features of AS include a happy demeanor, easily provoked laughter, short attention span, hypermotoric behavior, mouthing of objec...

  13. Distinct molecular mechanisms underlying clinically relevant subtypes of breast cancer: gene expression analyses across three different platforms

    Directory of Open Access Journals (Sweden)

    Naume Bjørn

    2006-05-01

    Full Text Available Abstract Background Gene expression profiling has been used to define molecular phenotypes of complex diseases such as breast cancer. The luminal A and basal-like subtypes have been repeatedly identified and validated as the two main subtypes out of a total of five molecular subtypes of breast cancer. These two are associated with distinctly different gene expression patterns and more importantly, a significant difference in clinical outcome. To further validate and more thoroughly characterize these two subtypes at the molecular level in tumors at an early stage, we report a gene expression profiling study using three different DNA microarray platforms. Results Expression data from 20 tumor biopsies of early stage breast carcinomas were generated on three different DNA microarray platforms; Applied Biosystems Human Genome Survey Microarrays, Stanford cDNA Microarrays and Agilent's Whole Human Genome Oligo Microarrays, and the resulting gene expression patterns were analyzed. Both unsupervised and supervised analyses identified the different clinically relevant subtypes of breast tumours, and the results were consistent across all three platforms. Gene classification and biological pathway analyses of the genes differentially expressed between the two main subtypes revealed different molecular mechanisms descriptive of the two expression-based subtypes: Signature genes of the luminal A subtype were over-represented by genes involved in fatty acid metabolism and steroid hormone-mediated signaling pathways, in particular estrogen receptor signaling, while signature genes of the basal-like subtype were over-represented by genes involved in cell proliferation and differentiation, p21-mediated pathway, and G1-S checkpoint of cell cycle-signaling pathways. A minimal set of 54 genes that best discriminated the two subtypes was identified using the combined data sets generated from the three different array platforms. These predictor genes were further

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

    Science.gov (United States)

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

    2014-04-25

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

  15. Electrostatic potential profile and nonlinear current in an interacting one-dimensional molecular wire

    Indian Academy of Sciences (India)

    S Lakshmi; Swapan K Pati

    2003-10-01

    We consider an interacting one-dimensional molecular wire attached to two metal electrodes on either side of it. The electrostatic potential profile across the wire-electrode interface has been deduced solving the Schrodinger and Poisson equations self-consistently. Since the Poisson distribution crucially depends on charge densities, we have considered different Hamiltonian parameters to model the nanoscale wire. We find that for very weak electron correlations, the potential gradient is almost zero in the middle of the wire but are large near the chain ends. However, for strong correlations, the potential is essentially a ramp function. The nonlinear current, obtained from the scattering formalism, is found to be less with the ramp potential than for weak correlations. Some of the interesting features in current-voltage characteristics have been explained using one-electron formalism and instabilities in the system.

  16. Prevalence and clinical profile of celiac disease in children with type 1 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Rajesh Joshi

    2015-01-01

    Full Text Available Objective: To determine the prevalence of celiac disease (CD in children with type 1 diabetes mellitus (TIDM in follow-up in a Tertiary Care Referral Centre in Western India and to describe the clinical features indicative of CD in screened patients of TIDM. Study Design: In this single center observational cross-sectional study, 71 children who were diagnosed with TIDM were subjected to screening for CD with tissue transglutaminase antibody testing. Those who tested positive were offered intestinal biopsy for the confirmation of diagnosis. Clinical profiles of both groups of patients were compared and manifestations of CD were delineated. Results: The study revealed the prevalence of CD (based on serology in children with Type 1 diabetes as 15.49%. The prevalence of biopsy-confirmed CD was 7.04%. Of the diagnosed CD patients, one-third were symptomatic at the time of screening while the majority was asymptomatic. The major clinical features indicative of CD were intestinal symptoms, anemia, rickets, and short stature. Autoimmune thyroid disease was prevalent in 29.6% of the patients with TIDM followed by CD. Conclusions: The high prevalence of CD in children with Type 1 diabetes emphasizes the need for routine screening programs to be in place for these high-risk populations. The clinical profile of patients with CD further elaborates the indicators of CD and the need to screen for them.

  17. Clinical profile of high-risk febrile neutropenia in a tertiary care hospital

    Directory of Open Access Journals (Sweden)

    Mohan V Bhojaraja

    2016-06-01

    Full Text Available Background Infection in the immunocompromised host has been a reason of concern in the clinical setting and a topic of debate for decades. In this study, the aim was to analyse the clinical profile of high-risk febrile neutropenic patients. Aims To study the clinical profile of high risk febrile neutropenia patients with the objective of identifying the most common associated malignancy, most common associated pathogen, the source of infection, to correlate the treatment and management with that of the Infectious Diseases Society of America (IDSA 2010 guidelines and to assess the clinical outcome. Methods A cross-sectional time bound study was carried out and a total of 80 episodes of high-risk febrile neutropenia were recorded among patients with malignancies from September 2011 to July 2013 with each episode being taken as a new case. Results Non-Hodgkin’s lymphoma (30 per cent was the most common malignancy associated, commonest source of infection was due to central venous catheters, the commonest pathogens were gram negative (52 per cent the treatment and management of each episode of high risk febrile neutropenia correlated with that of IDSA 2010 guidelines and the mortality rate was 13.75 per cent. Conclusion Febrile neutropenia is one of the major complications and cause of mortality in patients with malignancy and hence understanding its entire spectrum can help us reduce morbidity and mortality.

  18. Comprehensive profiling of DNA methylation in colorectal cancer reveals subgroups with distinct clinicopathological and molecular features

    International Nuclear Information System (INIS)

    Most previous studies of the CpG island methylator phenotype (CIMP) in colorectal cancer (CRC) have been conducted on a relatively small numbers of CpG sites. In the present study we performed comprehensive DNA methylation profiling of CRC with the aim of characterizing CIMP subgroups. DNA methylation at 1,505 CpG sites in 807 cancer-related genes was evaluated using the Illumina GoldenGate® methylation array in 28 normal colonic mucosa and 91 consecutive CRC samples. Methylation data was analyzed using unsupervised hierarchical clustering. CIMP subgroups were compared for various clinicopathological and molecular features including patient age, tumor site, microsatellite instability (MSI), methylation at a consensus panel of CpG islands and mutations in BRAF and KRAS. A total of 202 CpG sites were differentially methylated between tumor and normal tissue. Unsupervised hierarchical clustering of methylation data from these sites revealed the existence of three CRC subgroups referred to as CIMP-low (CIMP-L, 21% of cases), CIMP-mid (CIMP-M, 14%) and CIMP-high (CIMP-H, 65%). In comparison to CIMP-L tumors, CIMP-H tumors were more often located in the proximal colon and showed more frequent mutation of KRAS and BRAF (P < 0.001). Comprehensive DNA methylation profiling identified three CRC subgroups with distinctive clinicopathological and molecular features. This study suggests that both KRAS and BRAF mutations are involved with the CIMP-H pathway of CRC rather than with distinct CIMP subgroups

  19. Molecular depth profiling of organic photovoltaic heterojunction layers by ToF-SIMS: comparative evaluation of three sputtering beams.

    Science.gov (United States)

    Mouhib, T; Poleunis, C; Wehbe, N; Michels, J J; Galagan, Y; Houssiau, L; Bertrand, P; Delcorte, A

    2013-11-21

    With the recent developments in secondary ion mass spectrometry (SIMS), it is now possible to obtain molecular depth profiles and 3D molecular images of organic thin films, i.e. SIMS depth profiles where the molecular information of the mass spectrum is retained through the sputtering of the sample. Several approaches have been proposed for "damageless" profiling, including the sputtering with SF5(+) and C60(+) clusters, low energy Cs(+) ions and, more recently, large noble gas clusters (Ar500-5000(+)). In this article, we evaluate the merits of these different approaches for the in depth analysis of organic photovoltaic heterojunctions involving poly(3-hexylthiophene) (P3HT) as the electron donor and [6,6]-phenyl C61 butyric acid methyl ester (PCBM) as the acceptor. It is demonstrated that the use of 30 keV C60(3+) and 500 eV Cs(+) (500 eV per atom) leads to strong artifacts for layers in which the fullerene derivative PCBM is involved, related to crosslinking and topography development. In comparison, the profiles obtained using 10 keV Ar1700(+) (∼6 eV per atom) do not indicate any sign of artifacts and reveal fine compositional details in the blends. However, increasing the energy of the Ar cluster beam beyond that value leads to irreversible damage and failure of the molecular depth profiling. The profile qualities, apparent interface widths and sputtering yields are analyzed in detail. On the grounds of these experiments and recent molecular dynamics simulations, the discussion addresses the issues of damage and crater formation induced by the sputtering and the analysis ions in such radiation-sensitive materials, and their effects on the profile quality and the depth resolution. Solutions are proposed to optimize the depth resolution using either large Ar clusters or low energy cesium projectiles for sputtering and/or analysis.

  20. Diversity of Bipolaris species in clinical samples in the United States and their antifungal susceptibility profiles

    OpenAIRE

    Cunha, DA; Sutton, D.A.; Fothergill, A. W.; Cano, J.; Gene, J.; Madrid, H.; Hoog, de, G.S.; Crous, P.W.; Guarro, J

    2012-01-01

    A set of 104 isolates from human clinical samples from the United States, morphologically compatible with Bipolaris, were morphologically and molecularly identified through the sequence analysis of the internal transcribed space (ITS) region of the nuclear ribosomal DNA (rDNA). The predominant species was Bipolaris spicifera (67.3%), followed by B. hawaiiensis (18.2%), B. cynodontis (8.6%), B. micropus (2.9%), B. australiensis (2%), and B. setariae (1%). Bipolaris cynodontis, B. micropus, and...

  1. Molecular dynamics simulations and free energy profile of Paracetamol in DPPC and DMPC lipid bilayers

    Indian Academy of Sciences (India)

    Yousef Nademi; Sepideh Amjad Iranagh; Abbas Yousefpour; Seyedeh Zahra Mousavi; Hamid Modarress

    2014-05-01

    Molecular dynamics (MD) simulations and biased MD simulation were carried out for the neutral form of Paracetamol inserted in fully hydrated dipalmitoylphosphatidylcholine (DPPC) and dimyristoylphosphatidylcholine (DMPC) lipid bilayers. For comparison, fully hydrated DMPC and DPPC lipid bilayers were also simulated separately without Paracetamol. The simulation time for each system was 50 ns. At two concentrations of Paracetamol, various properties of the lipid bilayer such as area per lipid, order parameter, diffusion coefficient, radial distribution function, electrostatic potential, mass density and hydrogen bonds have been calculated. Also, the convergence in time of the free energy profile of the Paracetamol along a DPPC bilayer normal was calculated by umbrella sampling method. From the obtained results, it can be concluded that neutral form of Paracetamol shows a generally similar behaviour in DPPC and DMPC lipid bilayers. It was shown that the addition of Paracetamol causes a decrease in tail order parameter of both DPPC and DMPC lipid bilayers and the tail of Paracetamol adopts an inward orientation in the lipid bilayers. Also from the free energy profile, the high penetration barrier in the bilayer centre was determined.

  2. Deep RNA profiling identified CLOCK and molecular clock genes as pathophysiological signatures in collagen VI myopathy.

    Science.gov (United States)

    Scotton, Chiara; Bovolenta, Matteo; Schwartz, Elena; Falzarano, Maria Sofia; Martoni, Elena; Passarelli, Chiara; Armaroli, Annarita; Osman, Hana; Rodolico, Carmelo; Messina, Sonia; Pegoraro, Elena; D'Amico, Adele; Bertini, Enrico; Gualandi, Francesca; Neri, Marcella; Selvatici, Rita; Boffi, Patrizia; Maioli, Maria Antonietta; Lochmüller, Hanns; Straub, Volker; Bushby, Katherine; Castrignanò, Tiziana; Pesole, Graziano; Sabatelli, Patrizia; Merlini, Luciano; Braghetta, Paola; Bonaldo, Paolo; Bernardi, Paolo; Foley, Reghan; Cirak, Sebahattin; Zaharieva, Irina; Muntoni, Francesco; Capitanio, Daniele; Gelfi, Cecilia; Kotelnikova, Ekaterina; Yuryev, Anton; Lebowitz, Michael; Zhang, Xiping; Hodge, Brian A; Esser, Karyn A; Ferlini, Alessandra

    2016-04-15

    Collagen VI myopathies are genetic disorders caused by mutations in collagen 6 A1, A2 and A3 genes, ranging from the severe Ullrich congenital muscular dystrophy to the milder Bethlem myopathy, which is recapitulated by collagen-VI-null (Col6a1(-/-)) mice. Abnormalities in mitochondria and autophagic pathway have been proposed as pathogenic causes of collagen VI myopathies, but the link between collagen VI defects and these metabolic circuits remains unknown. To unravel the expression profiling perturbation in muscles with collagen VI myopathies, we performed a deep RNA profiling in bothCol6a1(-/-)mice and patients with collagen VI pathology. The interactome map identified common pathways suggesting a previously undetected connection between circadian genes and collagen VI pathology. Intriguingly,Bmal1(-/-)(also known asArntl) mice, a well-characterized model displaying arrhythmic circadian rhythms, showed profound deregulation of the collagen VI pathway and of autophagy-related genes. The involvement of circadian rhythms in collagen VI myopathies is new and links autophagy and mitochondrial abnormalities. It also opens new avenues for therapies of hereditary myopathies to modulate the molecular clock or potential gene-environment interactions that might modify muscle damage pathogenesis. PMID:26945058

  3. Deep RNA profiling identified CLOCK and molecular clock genes as pathophysiological signatures in collagen VI myopathy.

    Science.gov (United States)

    Scotton, Chiara; Bovolenta, Matteo; Schwartz, Elena; Falzarano, Maria Sofia; Martoni, Elena; Passarelli, Chiara; Armaroli, Annarita; Osman, Hana; Rodolico, Carmelo; Messina, Sonia; Pegoraro, Elena; D'Amico, Adele; Bertini, Enrico; Gualandi, Francesca; Neri, Marcella; Selvatici, Rita; Boffi, Patrizia; Maioli, Maria Antonietta; Lochmüller, Hanns; Straub, Volker; Bushby, Katherine; Castrignanò, Tiziana; Pesole, Graziano; Sabatelli, Patrizia; Merlini, Luciano; Braghetta, Paola; Bonaldo, Paolo; Bernardi, Paolo; Foley, Reghan; Cirak, Sebahattin; Zaharieva, Irina; Muntoni, Francesco; Capitanio, Daniele; Gelfi, Cecilia; Kotelnikova, Ekaterina; Yuryev, Anton; Lebowitz, Michael; Zhang, Xiping; Hodge, Brian A; Esser, Karyn A; Ferlini, Alessandra

    2016-04-15

    Collagen VI myopathies are genetic disorders caused by mutations in collagen 6 A1, A2 and A3 genes, ranging from the severe Ullrich congenital muscular dystrophy to the milder Bethlem myopathy, which is recapitulated by collagen-VI-null (Col6a1(-/-)) mice. Abnormalities in mitochondria and autophagic pathway have been proposed as pathogenic causes of collagen VI myopathies, but the link between collagen VI defects and these metabolic circuits remains unknown. To unravel the expression profiling perturbation in muscles with collagen VI myopathies, we performed a deep RNA profiling in both Col6a1(-/-)mice and patients with collagen VI pathology. The interactome map identified common pathways suggesting a previously undetected connection between circadian genes and collagen VI pathology. Intriguingly, Bmal1(-/-)(also known as Arntl) mice, a well-characterized model displaying arrhythmic circadian rhythms, showed profound deregulation of the collagen VI pathway and of autophagy-related genes. The involvement of circadian rhythms in collagen VI myopathies is new and links autophagy and mitochondrial abnormalities. It also opens new avenues for therapies of hereditary myopathies to modulate the molecular clock or potential gene-environment interactions that might modify muscle damage pathogenesis.

  4. CT-guided pericardiocenteses: Clinical profile, practice patterns and clinical outcome

    Energy Technology Data Exchange (ETDEWEB)

    Eichler, Katrin, E-mail: k.eichler@em.uni-frankfurt.d [Department of Diagnostic and Interventional Radiology, University of Frankfurt, Frankfurt (Germany); Zangos, Stephan; Thalhammer, Axel; Jacobi, Volkmar [Department of Diagnostic and Interventional Radiology, University of Frankfurt, Frankfurt (Germany); Walcher, Felix; Marzi, Ingo [Department of Trauma, Hand and Reconstructive Surgery, University of Frankfurt, Frankfurt (Germany); Moritz, Anton [Department of Thoracic and Cardiovascular Surgery, University of Frankfurt, Frankfurt (Germany); Vogl, Thomas J.; Mack, Martin G. [Department of Diagnostic and Interventional Radiology, University of Frankfurt, Frankfurt (Germany)

    2010-07-15

    Objective: To assess the effectiveness and clinical outcome and technique of CT-guided pericardiocenteses in the treatment of pericardial effusions in adults and children. Methods: 20 drainages were performed in Seldinger-technique under CT-guidance on 20 patients suffering from pericardial effusions and haematomas. In 85%, the etiology of effusion was postoperative. The mean age of the patients was 59 years (minimum 9 years, maximum 86 years).There were 12 male and eight female patients. The inclusion criterion was an echocardiographically relevant proved pericardial effusion. Results: All catheters could be placed successfully (20/20) in the pericardial effusion and allowed for draining of the effusion in all cases under CT-guidance. The overall 30-day mortality rate was 0%. CT-guided pericardiocentesis was successful for withdrawing pericardial fluid and/or relieving tamponade in 100% of all procedures. No major complication was occurred. A total of one minor complication (5%) occurred that required no specific interventions, except for monitoring and appropriate follow-up. We observed one pneumothorax as a minor complication. Conclusions: Pericardial effusions of various causes can be safely, effectively, and quickly managed with CT-guided pericardiocenteses in adults and children. The ventrolateral entry side for the puncture should be preferred to reach the whole effusion and avoid complications, like a pneumothorax.

  5. A standardized framework for the validation and verification of clinical molecular genetic tests.

    NARCIS (Netherlands)

    Mattocks, C.J.; Morris, M.A.; Matthijs, G.; Swinnen, E.; Corveleyn, A.; Dequeker, E.; Muller, C.R.; Pratt, V.; Wallace, A.

    2010-01-01

    The validation and verification of laboratory methods and procedures before their use in clinical testing is essential for providing a safe and useful service to clinicians and patients. This paper outlines the principles of validation and verification in the context of clinical human molecular gene

  6. Molecular and antimicrobial susceptibility analyses distinguish clinical from bovine Escherichia coli O157 strains.

    Science.gov (United States)

    Vidovic, Sinisa; Tsoi, Sarah; Medihala, Prabhakara; Liu, Juxin; Wylie, John L; Levett, Paul N; Korber, Darren R

    2013-07-01

    A population-based study combining (i) antimicrobial, (ii) genetic, and (iii) virulence analyses with molecular evolutionary analyses revealed segregative characteristics distinguishing human clinical and bovine Escherichia coli O157 strains from western Canada. Human (n = 50) and bovine (n = 50) strains of E. coli O157 were collected from Saskatchewan and Manitoba in 2006 and were analyzed by using the six-marker lineage-specific polymorphism assay (LSPA6), antimicrobial susceptibility analysis, the colicin assay, plasmid and virulence profiling including the eae, ehxA, espA, iha, stx1, stx2, stx2c, stx2d, stx2d-activatable, stx2e, and stx2f virulence-associated genes, and structure analyses. Multivariate logistic regression and Fisher's exact test strongly suggested that antimicrobial susceptibility was the most distinctive characteristic (P = 0.00487) associated with human strains. Among all genetic, virulence, and antimicrobial determinants, resistance to tetracycline (P coli O157 strains. Among 11 virulence-associated genes, stx2c showed the strongest association with E. coli O157 strains of bovine origin. LSPA6 genotyping showed the dominance of the lineage I genotype among clinical (90%) and bovine (70%) strains, indicating the importance of lineage I in O157 epidemiology and ecology. Population structure analysis revealed that the more-diverse bovine strains came from a unique group of strains characterized by a high degree of antimicrobial resistance and high frequencies of lineage II genotypes and stx2c variants. These findings imply that antimicrobial resistance generated among bovine strains of E. coli O157 has a large impact on the population of this human pathogen.

  7. Elucidation of the molecular responses to waterlogging in Jatropha roots by transcriptome profiling.

    Science.gov (United States)

    Juntawong, Piyada; Sirikhachornkit, Anchalee; Pimjan, Rachaneeporn; Sonthirod, Chutima; Sangsrakru, Duangjai; Yoocha, Thippawan; Tangphatsornruang, Sithichoke; Srinives, Peerasak

    2014-01-01

    Jatropha (Jatropha curcas) is a promising oil-seed crop for biodiesel production. However, the species is highly sensitive to waterlogging, which can result in stunted growth and yield loss. To date, the molecular mechanisms underlying the responses to waterlogging in Jatropha remain elusive. Here, the transcriptome adjustment of Jatropha roots to waterlogging was examined by high-throughput RNA-sequencing (RNA-seq). The results indicated that 24 h of waterlogging caused significant changes in mRNA abundance of 1968 genes. Comprehensive gene ontology and functional enrichment analysis of root transcriptome revealed that waterlogging promoted responses to hypoxia and anaerobic respiration. On the other hand, the stress inhibited carbohydrate synthesis, cell wall biogenesis, and growth. The results also highlighted the roles of ethylene, nitrate, and nitric oxide in waterlogging acclimation. In addition, transcriptome profiling identified 85 waterlogging-induced transcription factors including members of AP2/ERF, MYB, and WRKY families implying that reprogramming of gene expression is a vital mechanism for waterlogging acclimation. Comparative analysis of differentially regulated transcripts in response to waterlogging among Arabidopsis, gray poplar, Jatropha, and rice further revealed not only conserved but species-specific regulation. Our findings unraveled the molecular responses to waterlogging in Jatropha and provided new perspectives for developing a waterlogging tolerant cultivar in the future.

  8. Elucidation of the molecular responses to waterlogging in Jatropha roots by transcriptome profiling

    Directory of Open Access Journals (Sweden)

    Piyada eJuntawong

    2014-12-01

    Full Text Available Jatropha (Jatropha curcas is a promising oil-seed crop for biodiesel production. However, the species is highly sensitive to waterlogging, which can result in stunted growth and yield loss. To date, the molecular mechanisms underlying the responses to waterlogging in Jatropha remain elusive. Here, the transcriptome adjustment of Jatropha roots to waterlogging was examined by high-throughput RNA-sequencing (RNA-seq. The results indicated that 24 h of waterlogging caused significant changes in mRNA abundance of 1,968 genes. Comprehensive gene ontology and functional enrichment analysis of root transcriptome revealed that waterlogging promoted responses to hypoxia and anaerobic respiration. On the other hand, the stress inhibited carbohydrate synthesis, cell wall biogenesis, and growth. The results also highlighted the roles of ethylene, nitrate, and nitric oxide in waterlogging acclimation. In addition, transcriptome profiling identified 85 waterlogging-induced transcription factors including members of AP2/ERF, MYB, and WRKY families implying that reprogramming of gene expression is a vital mechanism for waterlogging acclimation. Comparative analysis of differentially regulated transcripts in response to waterlogging among Arabidopsis, gray poplar, Jatropha, and rice further revealed not only conserved but species-specific regulation. Our findings unraveled the molecular responses to waterlogging in Jatropha and provided new perspectives for developing a waterlogging tolerant cultivar in the future.

  9. Characterization and molecular profiling of PSEN1 familial Alzheimer's disease iPSC-derived neural progenitors.

    Directory of Open Access Journals (Sweden)

    Andrew A Sproul

    Full Text Available Presenilin 1 (PSEN1 encodes the catalytic subunit of γ-secretase, and PSEN1 mutations are the most common cause of early onset familial Alzheimer's disease (FAD. In order to elucidate pathways downstream of PSEN1, we characterized neural progenitor cells (NPCs derived from FAD mutant PSEN1 subjects. Thus, we generated induced pluripotent stem cells (iPSCs from affected and unaffected individuals from two families carrying PSEN1 mutations. PSEN1 mutant fibroblasts, and NPCs produced greater ratios of Aβ42 to Aβ40 relative to their control counterparts, with the elevated ratio even more apparent in PSEN1 NPCs than in fibroblasts. Molecular profiling identified 14 genes differentially-regulated in PSEN1 NPCs relative to control NPCs. Five of these targets showed differential expression in late onset AD/Intermediate AD pathology brains. Therefore, in our PSEN1 iPSC model, we have reconstituted an essential feature in the molecular pathogenesis of FAD, increased generation of Aβ42/40, and have characterized novel expression changes.

  10. Clinical and molecular phenotype of Aicardi-Goutieres syndrome

    NARCIS (Netherlands)

    Rice, Gillian; Patrick, Teresa; Parmar, Rekha; Taylor, Claire F.; Aeby, Alec; Aicardi, Jean; Artuch, Rafael; Montalto, Simon Attard; Bacino, Carlos A.; Barroso, Bruno; Baxter, Peter; Benko, Willam S.; Bergmann, Carsten; Bertini, Enrico; Biancheri, Roberta; Blair, Edward M.; Blau, Nenad; Bonthron, David T.; Briggs, Tracy; Brueton, Louise A.; Brunner, Han G.; Burke, Christopher J.; Carr, Ian M.; Carvalho, Daniel R.; Chandler, Kate E.; Christen, Hans-Juergen; Corry, Peter C.; Cowan, Frances M.; Cox, Helen; D'Arrigo, Stefano; Dean, John; De laet, Corinne; De Praeter, Claudine; Dery, Catherine; Ferrie, Colin D.; Flintoff, Kim; Frints, Suzanna G. M.; Garcia-Cazorla, Angels; Gener, Blanca; Goizet, Cyril; Goutieres, Francoise; Green, Andrew J.; Gueet, Agnes; Hamel, Ben C. J.; Hayward, Bruce E.; Heiberg, Arvid; Hennekam, Raoul C.; Husson, Marie; Jackson, Andrew P.; Jayatunga, Rasieka; Jiang, Yong-Hui; Kant, Sarina G.; Kao, Amy; King, Mary D.; Kingston, Helen M.; Klepper, Joerg; van der Knaap, Marjo S.; Kornberg, Andrew J.; Kotzot, Dieter; Kratzer, Wilfried; Lacombe, Didier; Lagae, Lieven; Landrieu, Pierre Georges; Lanzi, Giovanni; Leitch, Andrea; Lim, Ming J.; Livingston, John H.; Lourenco, Charles M.; Lyall, E. G. Hermione; Lynch, Sally A.; Lyons, Michael J.; Marom, Daphna; McClure, John P.; McWilliam, Robert; Melancon, Serge B.; Mewasingh, Leena D.; Moutard, Marie-Laure; Nischal, Ken K.; Ostergaard, John R.; Prendiville, Julie; Rasmussen, Magnhild; Rogers, R. Curtis; Roland, Dominique; Rosser, Elisabeth M.; Rostasy, Kevin; Roubertie, Agathe; Sanchis, Amparo; Schiffmann, Raphael; Scholl-Buergi, Sabine; Seal, Sunita; Shalev, Stavit A.; Corcoles, C. Sierra; Sinha, Gyan P.; Soler, Doriette; Spiegel, Ronen; Stephenson, John B. P.; Tacke, Uta; Tan, Tiong Yang; Till, Marianne; Tolmie, John L.; Tomlin, Pam; Vagnarelli, Federica; Valente, Enza Maria; Van Coster, Rudy N. A.; Van der Aa, Nathalie; Vanderver, Adeline; Vles, Johannes S. H.; Voit, Thomas; Wassmer, Evangeline; Weschke, Bernhard; Whiteford, Margo L.; Willemsen, Michel A. A.; Zankl, Andreas; Zuberi, Sameer M.; Orcesi, Simona; Fazzi, Elisa; Lebon, Pierre; Crow, Yanick J.

    2007-01-01

    Aicardi-Goutieres syndrome (AGS) is a genetic encephalopathy whose clinical features mimic those of acquired in utero viral infection. AGS exhibits locus heterogeneity, with mutations identified in genes encoding the 3'-> 5' exonuclease TREX1 and the three subunits of the RNASEH2 endonuclease comple

  11. Clinical and molecular phenotype of Aicardi-Goutieres syndrome

    DEFF Research Database (Denmark)

    Rice, Gillian; Patrick, Teresa; Parmar, Rekha;

    2007-01-01

    Aicardi-Goutieres syndrome (AGS) is a genetic encephalopathy whose clinical features mimic those of acquired in utero viral infection. AGS exhibits locus heterogeneity, with mutations identified in genes encoding the 3'-->5' exonuclease TREX1 and the three subunits of the RNASEH2 endonuclease com...

  12. Clinical and molecular insights into primary pediatric liver cancer

    NARCIS (Netherlands)

    V.B. Weeda

    2016-01-01

    This thesis aims to give insight into the clinical status quo of primary pediatric liver tumors and investigate signaling pathways that may be of importance for liver tumorigenesis. The most recent series of the International Childhood Liver Tumors Strategy Group (SIOPEL) of hepatocellular carcinoma

  13. Clinical and Molecular Characterization of Osteogenesis Imperfecta Type V

    Science.gov (United States)

    Brizola, Evelise; Mattos, Eduardo P.; Ferrari, Jessica; Freire, Patricia O.A.; Germer, Raquel; Llerena Jr, Juan C.; Félix, Têmis M.

    2015-01-01

    Osteogenesis imperfecta type V (OI-V) has a wide clinical variability, with distinct clinical/radiological features, such as calcification of the interosseous membrane (CIM) between the radius-ulna and/or tibia-fibula, hyperplastic callus (HPC) formation, dislocation of the radial head (DRH), and absence of dentinogenesis imperfecta (DI). Recently, a single heterozygous mutation (c.-14C>T) in the 5′UTR of the IFITM5 gene was identified to be causative for OI-V. Here, we describe 7 individuals from 5 unrelated families that carry the c.-14C>T IFITM5 mutation. The clinical findings in these cases are: absence of DI in all patients, presence of blue sclera in 2 cases, and 4 patients with DRH. Radiographic findings revealed HPC in 3 cases. All patients presented CIM between the radius and ulna, while 4 patients presented additional CIM between the tibia and fibula. Spinal fractures by vertebral compression were observed in all individuals. The proportion of cases identified with this mutation represents 4% of OI cases at our institution. The clinical identification of OI-V is crucial, as this mutation has an autosomal dominant inheritance with variable expressivity. PMID:26648832

  14. Comparison of Mutation Profiles in the Duchenne Muscular Dystrophy Gene among Populations: Implications for Potential Molecular Therapies

    Directory of Open Access Journals (Sweden)

    Luz Berenice López-Hernández

    2015-03-01

    Full Text Available Novel therapeutic approaches are emerging to restore dystrophin function in Duchenne Muscular Dystrophy (DMD, a severe neuromuscular disease characterized by progressive muscle wasting and weakness. Some of the molecular therapies, such as exon skipping, stop codon read-through and internal ribosome entry site-mediated translation rely on the type and location of mutations. Hence, their potential applicability worldwide depends on mutation frequencies within populations. In view of this, we compared the mutation profiles of the populations represented in the DMD Leiden Open-source Variation Database with original data from Mexican patients (n = 162 with clinical diagnosis of the disease. Our data confirm that applicability of exon 51 is high in most populations, but also show that differences in theoretical applicability of exon skipping may exist among populations; Mexico has the highest frequency of potential candidates for the skipping of exons 44 and 46, which is different from other populations (p < 0.001. To our knowledge, this is the first comprehensive comparison of theoretical applicability of exon skipping targets among specific populations.

  15. Microdialysis Sampling from Wound Fluids Enables Quantitative Assessment of Cytokines, Proteins, and Metabolites Reveals Bone Defect-Specific Molecular Profiles

    Science.gov (United States)

    Wissenbach, Dirk K.; Pfeiffer, Susanne E. M.; Baumann, Sven; Hofbauer, Lorenz C.; von Bergen, Martin; Kalkhof, Stefan; Rammelt, Stefan

    2016-01-01

    Bone healing involves a variety of different cell types and biological processes. Although certain key molecules have been identified, the molecular interactions of the healing progress are not completely understood. Moreover, a clinical routine for predicting the quality of bone healing after a fracture in an early phase is missing. This is mainly due to a lack of techniques to comprehensively screen for cytokines, growth factors and metabolites at their local site of action. Since all soluble molecules of interest are present in the fracture hematoma, its in-depth assessment could reveal potential markers for the monitoring of bone healing. Here, we describe an approach for sampling and quantification of cytokines and metabolites by using microdialysis, combined with solid phase extractions of proteins from wound fluids. By using a control group with an isolated soft tissue wound, we could reveal several bone defect-specific molecular features. In bone defect dialysates the neutrophil chemoattractants CXCL1, CXCL2 and CXCL3 were quantified with either a higher or earlier response compared to dialysate from soft tissue wound. Moreover, by analyzing downstream adaptions of the cells on protein level and focusing on early immune response, several proteins involved in the immune cell migration and activity could be identified to be specific for the bone defect group, e.g. immune modulators, proteases and their corresponding inhibitors. Additionally, the metabolite screening revealed different profiles between the bone defect group and the control group. In summary, we identified potential biomarkers to indicate imbalanced healing progress on all levels of analysis. PMID:27441377

  16. Antimicrobial resistance profiling and molecular subtyping of Campylobacter spp. from processed turkey

    Directory of Open Access Journals (Sweden)

    Sherwood Julie S

    2009-09-01

    Ciprofloxacin and erythromycin resistance in Campylobacter recovered from processed turkey occurred more frequently among C. coli than C. jejuni. Fla-PFGE types were associated with a particular species, antimicrobial resistance profiles, and a specific plant. Molecular subtyping in this study provided more information about the relationships among antimicrobial-resistant Campylobacter at the processing level.

  17. A STUDY ON CLINICAL, LABORATORY PROFILE AND OUTCOME OF DENGUE FEVER

    Directory of Open Access Journals (Sweden)

    Vanamali

    2013-12-01

    Full Text Available ABSTRACT: BACKGROUND AND OBJECTIVES : In recent days there is an alarming increase in the incidence of dengue fever and has emerged as a serious international public health threat with almost half of the world's population at risk for infection . Very few studies have been conducted in this part of our country and hence this study was undertaken to study the clinical picture, la boratory profile and outcome of dengue fever in and around khammam. MATERIALS AND METHODS: A prospective study was conducted over one year at Mamata General Hospital, during which 190 cases were diagnosed as dengue fever which were taken into study and eval uated for clinical, laboratory profile and their outcome. RESULTS : Out of 190 patients taken into study, fever was the most common presentation followed by headache. Thrombocytopenia was seen in 75% of the patients. Bleeding manifestations were seen in pat ients with platelet counts less than 40000/mm 3 . 18 patients were diagnosed as DHF, 6 patients were diagnosed as DSS. During our study 10 patients expired. CONCLUSION: The clinical and hematological picture of dengue fever is like any other viral fevers and the bleeding manifestations are seen in patients whose platelet counts decreases less than 40000/mm 3 only

  18. Molecular Screening of Staphylococcal Enterotoxin B Gene in Clinical Isolates

    Directory of Open Access Journals (Sweden)

    Ali Karami

    2011-01-01

    Full Text Available Objective: The role of staphylococcal enterotoxin B (SEB in food poisoning is well known,however its role in other diseases remains to be explored. The aim of this study is the molecularscreening and characterization of the SEB gene in clinically isolated strains.Materials and Methods: In this experimentally study, 300 Staphylococcus aureus (S.aureus strains isolated from clinical samples were assayed. The isolated strains wereconfirmed by conventional bacteriological methods. Polymerase chain reaction (PCRwas used to determine the enterotoxin B (ent B gene. Assessment of toxin productionin all strains that contained the ent B gene was then performed. Finally, using specificantibody against SEB, a Western-blot was applied to confirm detection of enterotoxin Bproduction.Results: Results indicated that only 5% of the 300 clinically isolated S. aureus containedthe ent B gene. All strains which contained the ent B gene produced a proteinous enterotoxinB. The results of sequence determination of the PCR product were compared withthe gene bank database and 98% similarity was achieved. The results of the Western-blotconfirmed that enterotoxin B was produced in strains that contained the ent B gene.Conclusion: The results of this study indicate that 5% of clinically isolated S. aureusstrains produce enterotoxin B. Considering that the enterotoxin B is an important superantigen,it is possible that a delay in diagnosis and lack of early proper treatment can causean incidence of late complications, particularly in staphylococcal chronic infections. Forthis reason, it is suggested that in addition to detecting bacteria, an enterotoxin B detectiontest should be performed to control its toxigenicity.

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

    OpenAIRE

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

    2012-01-01

    Background Morgellons is a poorly characterized constellation of symptoms, with the primary manifestations involving the skin. We conducted an investigation of this unexplained dermopathy to characterize the clinical and epidemiologic features and explore potential etiologies. Methods A descriptive study was conducted among persons at least 13 years of age and enrolled in Kaiser Permanente Northern California (KPNC) during 2006–2008. A case was defined as the self-reported emergence of fibers...

  20. Clinical and molecular insights into primary pediatric liver cancer

    OpenAIRE

    Weeda, V.B.

    2016-01-01

    This thesis aims to give insight into the clinical status quo of primary pediatric liver tumors and investigate signaling pathways that may be of importance for liver tumorigenesis. The most recent series of the International Childhood Liver Tumors Strategy Group (SIOPEL) of hepatocellular carcinoma (HCC) and its distinct variant fibrolamellar hepatocellular carcinoma (FL-HCC) are discussed. For both tumors, complete resection is at present the only curative option. FL-HCC does not have a bet...

  1. Molecular/clinical correlations in females with fragile X

    Energy Technology Data Exchange (ETDEWEB)

    Sobesky, W.E.; Riddle, J.; Hagerman, R.J. [Children`s Hospital, Denver, CO (United States)] [and others

    1996-08-09

    Females who are affected by fragile X syndrome (FXS) can have significant physical, neuropsychological and emotional involvement. This study was designed to explore the relationships between these three domains and to learn how the degree of involvement in each of these phenotypic areas relates to molecular parameters including CGG repeat length and activation ratio (the proportion of normal FMR1 alleles on the active X chromosome). Three groups of females were studied: 35 women who grew up in a fragile X family but do not carry an FMR1 mutation, 92 women with a premutation, and 29 women with a full mutation. Correlations between neurocognitive, physical and emotional traits were calculated for each of the three groups. Within the full mutation group significant correlations were seen between schizotypal traits and full scale IQ. The Lie scale was significantly correlated with the physical findings index. The activation ratio correlated significantly with the measure of executive function (r = .50, P = .01). There was a trend toward correlations of activation ratio with the physical index score, outer ear prominence and IQ. CGG repeat number significantly correlated only with the physical index (r = .44, P = .0 1). Thus, activation ratio may be the more pertinent molecular parameter in full mutation women in determining the degree of cognitive and physical phenotypic involvement. 29 refs., 2 tabs.

  2. Clinical profile of primary hyperparathyroidism from western India: A single center experience

    Directory of Open Access Journals (Sweden)

    Gopal R

    2010-01-01

    Full Text Available Background: Primary hyperparathyroidism (PHPT has a variable clinical presentation and symptomatic PHPT is still the predominant form of the disease in India. Data from western India is lacking. Aim : To present the clinical profile of PHPT from western India. Settings and Design : This retrospective study was conducted at a tertiary care referral center. Materials and Methods : We analyzed the clinical presentation, biochemical, radiological features, and operative findings in adult patients with PHPT (1986-2008 and compared with our published data of children and adolescent patients with PHPT. Statistical Analysis : was done with SPSS 16 software. Results : Seventy-nine patients (F: M-2:1 with age ranging from 21 to 55 years (mean 33.5±8.82 were analyzed. Skeletal manifestations (75.5%, renal calculi (40.5% and proximal muscle weakness (45.5% were the most common symptoms of presentation with mean duration of symptoms being 33.70 (median: 24, range 1-120 months. Biochemical features included hypercalcemia (total corrected calcium 12.55±1.77 mg/dl, low inorganic phosphorus (1.81±0.682 mg/dl, elevated total alkaline phosphatase (mean: 762.2; median: 559; range: 50-4930IU/L and high parathyroid hormone (PTH (mean±SD: 866.61±799.15; median: 639.5; range: 52-3820 pg/ml. Preoperative localization was achieved in 74 patients and single adenoma was found during surgery in 72 patients. Hungry bone disease was seen in 30.3% and transient hypoparathyroidism developed in 62% patients. In comparison to PHPT in children there were no significant differences with regard to clinical, laboratory and radiological features. Conclusions : PHPT in western India is symptomatic disorder with skeletal and renal mani-festations at a much younger age. Clinical profile of PHPT in children is similar to that of adults.

  3. Evaluation of clinical, laboratory, and electrophoretic profiles for diagnosis of malnutrition in hospitalized dogs

    Directory of Open Access Journals (Sweden)

    Andrei Kelliton Fabretti

    2015-02-01

    Full Text Available Malnutrition is a major factor associated with increased rates of mortality and readmission, longer hospital stays, and greater health care spending. Recognizing malnourished or at-risk animals allows for nutritional intervention and improved prognosis. This study evaluated the association between clinical, laboratory, and electrophoretic variables and the nutritional status (NS of hospitalized dogs in order to generate a profile of the sick dog and to facilitate the diagnosis of malnutrition. We divided 215 dogs into groups according to the severity of the underlying disease and we determined the clinical NS based on the assessment of the body condition score and the muscle mass score. The NS was classified as clinically well nourished, clinical moderate malnutrition, or clinical severe malnutrition. Statistical analyses were conducted by using the chi-square test or Fisher’s exact test; the Kruskal-Wallis test was used for continuous variables. A strong association was found between malnutrition and the severity of the underlying disease. In hospitalized dogs, low body mass index values, anemia, low hemoglobin concentrations, high fibrinogen concentrations, decreased albumin fraction, and increased gamma-globulin fraction (in electrophoresis were associated with malnutrition, reinforcing the classification of poor NS. However, the skin and coat characteristics, the total number of lymphocytes, blood glucose, cholesterol, and total protein concentration were not found to be good predictors of NS.

  4. CLINICAL PROFILE AND MANAGEMENT AUDIT OF EAR WAX IMPACTION IN OWERRI, SOUTH EAST NIGERIA

    Directory of Open Access Journals (Sweden)

    IBIAM FA

    2014-10-01

    Full Text Available Ear wax impaction is a common daily otolaryngology clinic presentation cutting across age group, sex and race, yet our sub-region has little knowledge and research on this common disease. Objective: To clinically profile patients with ear wax and audit our current management practice in the Federal Medical Centre Owerri, South East Nigeria and to make recommendation where appropriate. Design. Hospital based retrospective study. Setting: Federal Medical Center Owerri, South East Nigeria. Subjects/Participants: Patients clinically diagnosed with ear wax impaction from January to December 2010. ResultsA total of 338 patients presented with ear wax, of the 3,375 patients that attended the ENT clinic during the period under review accounting for 10.01% prevalence rate. 150 (44.4% were males while 188 (55.6% were females giving a M:F ratio of 1:1.3. Commonest predisposing factor was cotton swab abuse in 26 (7.7% patients. Aural syringing after use of cerumenolytic agents in 272 (80.5% patients with wax impaction was the commonest treatment modality. There were no recorded complications. Conclusion: Ear wax impaction is a common clinical entity in our sub-region. Treatment is simple and safe; but ignorance remains a major challenge.

  5. "Do I Know What I Need to Do?" A Social Communication Intervention for Children with Complex Clinical Profiles

    Science.gov (United States)

    Timler, Geralyn R.; Olswang, Lesley B.; Coggins, Truman E.

    2005-01-01

    Purpose: Speech-language pathologists frequently address social communication difficulties in children with diverse clinical profiles. The purpose of this study was to investigate the feasibility of a social communication intervention for a school-age child with a complex cognitive and behavioral profile secondary to diagnosis of a fetal alcohol…

  6. Asperger syndrome in India: Findings from a case-series with respect to clinical profile and comorbidity

    OpenAIRE

    Priya Sreedaran; M V Ashok

    2015-01-01

    Asperger syndrome (AS) is an autism spectrum disorder with a high rate of psychiatric comorbidity. We describe the clinical profile and psychiatric comorbidity in a series of affected individuals referred to an Indian general hospital psychiatry setting. Gilliam Asperger's disorder scale was used to evaluate the clinical characteristics while Mini-International Neuropsychiatric Interview (MINI)-KID and MINI-PLUS were used to assess psychiatric comorbidity. The profile of subjects with AS in o...

  7. [Clinical and molecular genetic analysis of hereditary optic neuropathies].

    Science.gov (United States)

    Avetisov, S É; Sheremet, N L; Vorob'eva, O K; Eliseeva, É G; Chukhrova, A L; Loginova, A N; Khanakova, N A; Poliakov, A V

    2013-01-01

    DNA samples of 50 patients with optic neuropathy (ON) associated with congenital cataract were studied to find 3 major mt-DNA mutations (m.11778G>A, m.3460G>A, m.14484T>C), mutations in "hot" regions of OPA 1 gene (exons 8, 14, 15, 16, 18, 27, 28) and in the entire coding sequence of OPA3 gene for molecular genetic confirmation of diagnosis of hereditary Leber and autosomal dominant ON. Primary mutations of mtDNA responsible for hereditary Leber ON were found in 16 patients (32%). Pathogenic mutations of OPAl gene (c.869G>A and c. 2850delT) were identified in 2 patients (4%), these mutations were not found in the literature. OPA3 gene mutations were not revealed.

  8. Molecular Obstacles to Clinical Translation of iPSCs.

    Science.gov (United States)

    Tapia, Natalia; Schöler, Hans R

    2016-09-01

    The ability to reprogram somatic cells into induced pluripotent stem cells (iPSCs) using defined factors provides new tools for biomedical research. However, some iPSC clones display tumorigenic and immunogenic potential, thus raising concerns about their utility and safety in the clinical setting. Furthermore, variability in iPSC differentiation potential has also been described. Here we discuss whether these therapeutic obstacles are specific to transcription-factor-mediated reprogramming or inherent to every cellular reprogramming method. Finally, we address whether a better understanding of the mechanism underlying the reprogramming process might improve the fidelity of reprogramming and, therefore, the iPSC quality. PMID:27452174

  9. Exposure to low dose ionising radiation: Molecular and clinical consequences.

    LENUS (Irish Health Repository)

    Martin, Lynn M

    2014-07-10

    This review article provides a comprehensive overview of the experimental data detailing the incidence, mechanism and significance of low dose hyper-radiosensitivity (HRS). Important discoveries gained from past and present studies are mapped and highlighted to illustrate the pathway to our current understanding of HRS and the impact of HRS on the cellular response to radiation in mammalian cells. Particular attention is paid to the balance of evidence suggesting a role for DNA repair processes in the response, evidence suggesting a role for the cell cycle checkpoint processes, and evidence investigating the clinical implications\\/relevance of the effect.

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

    Science.gov (United States)

    Maggi, Lorenzo; Carboni, Nicola; Bernasconi, Pia

    2016-01-01

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

  11. The Spectrum of Clinical Utilities in Molecular Pathology Testing Procedures for Inherited Conditions and Cancer: A Report of the Association for Molecular Pathology.

    Science.gov (United States)

    Joseph, Loren; Cankovic, Milena; Caughron, Samuel; Chandra, Pranil; Emmadi, Rajyasree; Hagenkord, Jill; Hallam, Stephanie; Jewell, Kay E; Klein, Roger D; Pratt, Victoria M; Rothberg, Paul G; Temple-Smolkin, Robyn L; Lyon, Elaine

    2016-09-01

    Clinical utility describes the benefits of each laboratory test for that patient. Many stakeholders have adopted narrow definitions for the clinical utility of molecular testing as applied to targeted pharmacotherapy in oncology, regardless of the population tested or the purpose of the testing. This definition does not address all of the important applications of molecular diagnostic testing. Definitions consistent with a patient-centered approach emphasize and recognize that a clinical test result's utility depends on the context in which it is used and are particularly relevant to molecular diagnostic testing because of the nature of the information they provide. Debates surrounding levels and types of evidence needed to properly evaluate the clinical value of molecular diagnostics are increasingly important because the growing body of knowledge, stemming from the increase of genomic medicine, provides many new opportunities for molecular testing to improve health care. We address the challenges in defining the clinical utility of molecular diagnostics for inherited diseases or cancer and provide assessment recommendations. Starting with a modified analytic validity, clinical validity, clinical utility, and ethical, legal, and social implications model for addressing clinical utility of molecular diagnostics with a variety of testing purposes, we recommend promotion of patient-centered definitions of clinical utility that appropriately recognize the valuable contribution of molecular diagnostic testing to improve patient care. PMID:27542512

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

    DEFF Research Database (Denmark)

    Søes, Lillian Marie; Brock, Inger; Persson, Søren;

    2012-01-01

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

  13. Molecular and stimulus-response profiles illustrate heterogeneity between peripheral and cord blood-derived human mast cells

    DEFF Research Database (Denmark)

    Jensen, Bettina M; Frandsen, Pernille; Raaby, Ellen Margrethe Nedergaard;

    2014-01-01

    Different protocols exist for in vitro development of HuMCs from hematopoietic stem cells, which results in distinct mast cells regarding molecular markers and activation patterns. Here, we introduce a SR profile using immunological, neurogenic, and pharmacological stimuli to characterize cellula...

  14. Considerations for Implementation of Cancer Molecular Diagnostics Into Clinical Care.

    Science.gov (United States)

    Hayes, Daniel F

    2016-01-01

    Physicians have provided personalized care with as much precision as possible for several centuries. However, increasingly sophisticated understanding of the human genome and of cancer biology has permitted identification of genetic and phenotypic distinctions that might permit development of new tumor biomarker tests for risk categorization, screening, differential diagnosis, prognosis, prediction, and monitoring. Both commercial and academic laboratories are offering tests for single analytes, panels of tests of single analytes, multiparameter assays coalesced into a signature, and total genomic, transcriptomic, or proteomic analyses. However, the absence of a consistent regulatory environment has led to marketing of assays without proven analytic validity or clinical utility. U.S. Food and Drug Administration (FDA) approval or clearance does not necessarily imply that use of the test will improve patient outcomes, and FDA discretion to permit laboratory-developed tests results in unknown benefit, or harm, of others. In this regard, a "bad tumor marker is as bad as a bad drug." Caveat emptor is not a satisfactory approach to delivering high-quality care. Rather, adoption of tumor biomarker tests should be based on high levels of evidence generated in scientifically rigorous studies that demonstrate both analytical validity and clinical utility. Doing so will ensure that clinicians and patients are confident that a tumor biomarker test is likely to improve their outcomes. PMID:27249708

  15. PCA3: from basic molecular science to the clinical lab.

    Science.gov (United States)

    Day, John R; Jost, Matthias; Reynolds, Mark A; Groskopf, Jack; Rittenhouse, Harry

    2011-02-01

    Prostate cancer is the second leading cause of cancer deaths in men in the United States. Use of the serum prostate specific antigen (PSA) test to screen men for prostate cancer since the late 1980s has improved the early detection of prostate cancer, however low specificity of the test translates to numerous false positive results and many unnecessary biopsies. New biomarkers to aid in prostate cancer diagnosis are emerging and prostate cancer gene 3 (PCA3) is one such marker. PCA3 is a noncoding RNA that is highly over-expressed in prostate cancer tissue compared to benign tissue. A non-invasive test for PCA3 was developed using whole urine collected after a digital rectal exam (DRE). Numerous clinical studies have demonstrated the utility of PCA3 for the diagnosis of prostate cancer and some studies suggest that PCA3 may also have prognostic value. The use of PCA3 in combination with serum PSA and other clinical information enhances the diagnostic accuracy of prostate cancer detection and will enable physicians to make more informed decisions with patients at risk for prostate cancer.

  16. Cellular and molecular inflammatory profile of the choroid plexus in depression and suicide

    Directory of Open Access Journals (Sweden)

    Julia eDevorak

    2015-10-01

    Full Text Available The inflammatory hypothesis of depression is one of the main theories that endeavors to explain and describe the underlying biological mechanisms of depression and suicide. While mounting evidence indicates altered peripheral and central inflammatory profiles in depressed patients and suicide completers, little is known about how peripheral and central inflammation might be linked in these contexts. The choroid plexus (ChP, a highly vascularized tissue that produces cerebrospinal fluid (CSF and lacks a blood-brain-barrier, is an interface between peripheral and central immune responses. In the present study, we investigated the cellular and molecular inflammatory profile of the ChP of the lateral ventricle in depressed suicides and psychiatrically healthy controls. Gene expression of macrophages, pro- and anti-inflammatory cytokines, and various factors implicated in immune cell trafficking were measured; and density of ionized calcium binding adaptor molecule 1-positive (Iba1+ macrophages associated with the ChP epithelial cell layer (ECL was examined. Significant downregulations of the genes encoding interleukin 1ß (IL1ß, a pro-inflammatory acute-phase protein; intercellular cell adhesion molecule 1 (ICAM1, a protein implicated in immune cell trafficking in the ChP; and IBA1, a monocyte/macrophage marker; were detected in depressed suicides as compared to controls. No difference in the density of Iba1+ macrophages associated with the ChP ECL was observed. While interpretation of these findings is challenging in the absence of corroborating data from the CSF, peripheral blood, or brain parenchyma of the present cohort, we hypothesize that these present findings reflect a ChP compensatory mechanism that attenuates the detrimental effects of chronically altered pro-inflammatory signaling caused by elevated levels of pro-inflammatory cytokines, such as IL-1ß, peripherally and/or centrally. Together, these findings further implicate neuroimmune

  17. Clinical, epidemiologic, histopathologic and molecular features of an unexplained dermopathy.

    Directory of Open Access Journals (Sweden)

    Michele L Pearson

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

  18. Clinical, Molecular, and Environmental Risk Factors for Hodgkin Lymphoma

    Directory of Open Access Journals (Sweden)

    Alison Maggioncalda

    2011-01-01

    Full Text Available Epidemiological studies suggest unique occurrence patterns of Hodgkin lymphoma (HL worldwide. In most Western countries there is a clear bimodal age distribution with an early peak in young adults followed by a second peak in older adults, particularly among males. In the Middle East and Asia, HL is more common in early childhood. There also are marked racial differences in the presentations of HL and HL subtypes, and particular single nucleotide polymorphisms (SNPs have been identified as etiological factors suggesting that gene-gene and gene-environment interactions are involved. Personal health choices such as exercise and smoking may modify an individual's chances of developing HL. Numerous studies highlight the impact that exposure to Epstein-Barr virus and other environmental factors have on HL risk. Understanding the relative importance of each of these findings and their links to HL development and survival will help clinical researchers expand curative therapies and create preventative strategies for HL.

  19. Heterogeneity of white adipose tissue: molecular basis and clinical implications.

    Science.gov (United States)

    Kwok, Kelvin H M; Lam, Karen S L; Xu, Aimin

    2016-03-11

    Adipose tissue is a highly heterogeneous endocrine organ. The heterogeneity among different anatomical depots stems from their intrinsic differences in cellular and physiological properties, including developmental origin, adipogenic and proliferative capacity, glucose and lipid metabolism, insulin sensitivity, hormonal control, thermogenic ability and vascularization. Additional factors that influence adipose tissue heterogeneity are genetic predisposition, environment, gender and age. Under obese condition, these depot-specific differences translate into specific fat distribution patterns, which are closely associated with differential cardiometabolic risks. For instance, individuals with central obesity are more susceptible to developing diabetes and cardiovascular complications, whereas those with peripheral obesity are more metabolically healthy. This review summarizes the clinical and mechanistic evidence for the depot-specific differences that give rise to different metabolic consequences, and provides therapeutic insights for targeted treatment of obesity.

  20. Molecular profiling of cutaneous squamous cell carcinomas and actinic keratoses from organ transplant recipients

    International Nuclear Information System (INIS)

    The risk of developing cutaneous squamous cell carcinoma (SCC) is markedly increased in organ transplant recipients (OTRs) compared to the normal population. Next to sun exposure, the immunosuppressive regimen is an important risk factor for the development of SCC in OTRs. Various gene mutations (e.g. TP53) and genetic alterations (e.g. loss of CDKN2A, amplification of RAS) have been found in SCCs. The aim of this genome-wide study was to identify pathways and genomic alterations that are consistently involved in the formation of SCCs and their precursor lesions, actinic keratoses (AKs). To perform the analysis in an isogenic background, RNA and DNA were isolated from SCC, AK and normal (unexposed) epidermis (NS) from each of 13 OTRs. Samples were subjected to genome-wide expression analysis and genome SNP analysis using Illumina’s HumanWG-6 BeadChips and Infinium II HumanHap550 Genotyping BeadChips, respectively. mRNA expression results were verified by quantitative PCR. Hierarchical cluster analysis of mRNA expression profiles showed SCC, AK and NS samples to separate into three distinct groups. Several thousand genes were differentially expressed between epidermis, AK and SCC; most upregulated in SCCs were hyperproliferation related genes and stress markers, such as keratin 6 (KRT6), KRT16 and KRT17. Matching to oncogenic pathways revealed activation of downstream targets of RAS and cMYC in SCCs and of NFκB and TNF already in AKs. In contrast to what has been reported previously, genome-wide SNP analysis showed very few copy number variations in AKs and SCCs, and these variations had no apparent relationship with observed changes in mRNA expression profiles. Vast differences in gene expression profiles exist between SCC, AK and NS from immunosuppressed OTRs. Moreover, several pathways activated in SCCs were already activated in AKs, confirming the assumption that AKs are the precursor lesions of SCCs. Since the drastic changes in gene expression appeared

  1. 47,XXX male: A clinical and molecular study.

    Science.gov (United States)

    Ogata, T; Matsuo, M; Muroya, K; Koyama, Y; Fukutani, K

    2001-02-01

    We report a 53-year-old Japanese male with a 47,XXX karyotype. His clinical features included hypoplastic scrotal testes (4 ml bilaterally), normally formed small penis (3.8 cm), relatively poor pubic hair development (Tanner stage 3), gynecomastia, age-appropriate male height (159.1 cm), and mental retardation (verbal IQ of 56). Serum testosterone was markedly reduced (0.6 nmol/L). A needle biopsy showed severe testicular degeneration. FISH analysis revealed complex mosaicism consisting of (1) 47,XXX cells with a single copy of SRY (n = 177), two copies of SRY (n = 3), and no SRY (n = 1); (2) 46,XX cells with a single copy of SRY (n = 9) and no SRY (n = 3); (3) 45,X cells with no SRY (n = 5); and (4) 48,XXXX cells with a single copy of SRY (n = 1) and two copies of SRY (n = 1). PCR analysis showed the presence of Yp portion with the breakpoint between DYS264 and AMELY. Microsatellite analysis demonstrated three alleles for DMD and AR. X-inactivation analysis for the methylation status of the AR gene showed random inactivation of the three X chromosomes. The results suggest that this 47,XXX male has resulted from abnormal X-Y interchange during paternal meiosis and X-X nondisjunction during maternal meiosis. Complex mosaicism may be due to the age-related increase in mitotic nondisjunction which is prone to occur in rapidly dividing lymphocytes and to the presence of two randomly inactivated X chromosomes which may behave asynchronously during mitosis, and clinical features of this male would primarily be explained by the genetic information on the SRY (+) der(X) chromosome and his advanced age.

  2. Clinical applications of molecular basis for Craniosynostosis. A narrative review.

    Directory of Open Access Journals (Sweden)

    Saúl Ernesto Cifuentes-Mendiola

    2016-04-01

    Full Text Available Cranial sutures are specialized structures composed of the sutural mesenchyme, the overlying scalp, the dura and osteogenic fronts. Each one of these structures express important proteins for osteogenic maturation, membranous ossification of skull bones, and homeostasis of cranial sutures in a differential, spatial and temporal manner. These proteins include fibroblast growth factor (FGF and its receptors (FGFR, the transforming growth factor beta (TGF-β, bone morphogenetic proteins (BMPs, as well as transcription factors TWIST and MSX2, among others. The alteration in the expression of one or more of these proteins causes multiple pathological conditions; one of them is the premature closure of one or more cranial sutures, known as craniosynostosis. This malformation is commonly treated with surgery. However, advances in the fields of molecular and cellular biology have allowed to conduct research on some proteins involved in the development of craniosynostosis. The results of these studies can lead to future preventive therapeutic strategies that may be used as a complement to the surgical treatment of craniosynostosis. Possible strategies include the use of specific drugs that can regulate the expression and activation of FGF signaling pathways, TGF-β or BMPs, to prevent or avoid craniosynostosis or re-synostosis after a surgery.

  3. Molecular epidemiology of Mycobacterium tuberculosis clinical isolates in Southwest Ireland.

    LENUS (Irish Health Repository)

    Ojo, Olabisi O

    2010-10-01

    Tuberculosis has had significant effects on Ireland over the past two centuries, causing persistently higher morbidity and mortality than in neighbouring countries until the last decade. This study describes the results of genotyping and drug susceptibility testing of 171 strains of Mycobacterium tuberculosis complex isolated between January 2004 and December 2006 in a region of Ireland centred on the city of Cork. Spoligotype comparisons were made with the SpolDB4 database and clustered 130 strains in 23 groups, forty-one strains showed unique Spoligotyping patterns. The commonest spoligotypes detected were ST0137 (X2) (16.9%), and ST0351 (15.8%) (\\'U\\' clade). The major spoligotype clades were X (26.2%), U (19.3%), T (15.2%), Beijing (5.9%), Haarlem (4.7%), LAM (4.1%), BOVIS (1.75%), with 12.9% unassigned strains. A 24-locus VNTR genotyping produced 15 clusters containing 49 isolates, with high discrimination index (HGDI>0.99). A combination of Spoligotyping and VNTR reduced the number of clustered isolates to 47 in 15 clusters (27.5%). This study identified ST351 as common among Irish nationals, and found a low rate of drug resistance with little evidence of transmission of drug resistant strains. Strain clustering was significantly associated with age under 55 years and Irish nationality. Only strains of Euro-American lineage formed clusters. Molecular typing did not completely coincide with the results of contact investigations.

  4. PET Imaging - from Physics to Clinical Molecular Imaging

    Science.gov (United States)

    Majewski, Stan

    2008-03-01

    From the beginnings many years ago in a few physics laboratories and first applications as a research brain function imager, PET became lately a leading molecular imaging modality used in diagnosis, staging and therapy monitoring of cancer, as well as has increased use in assessment of brain function (early diagnosis of Alzheimer's, etc) and in cardiac function. To assist with anatomic structure map and with absorption correction CT is often used with PET in a duo system. Growing interest in the last 5-10 years in dedicated organ specific PET imagers (breast, prostate, brain, etc) presents again an opportunity to the particle physics instrumentation community to contribute to the important field of medical imaging. In addition to the bulky standard ring structures, compact, economical and high performance mobile imagers are being proposed and build. The latest development in standard PET imaging is introduction of the well known TOF concept enabling clearer tomographic pictures of the patient organs. Development and availability of novel photodetectors such as Silicon PMT immune to magnetic fields offers an exciting opportunity to use PET in conjunction with MRI and fMRI. As before with avalanche photodiodes, particle physics community plays a leading role in developing these devices. The presentation will mostly focus on present and future opportunities for better PET designs based on new technologies and methods: new scintillators, photodetectors, readout, software.

  5. Blood antioxidant profile and lipid peroxides in dairy cows with clinical mastitis

    Directory of Open Access Journals (Sweden)

    Rajesh Rathore

    2013-10-01

    Full Text Available Aim: To evaluate blood antioxidant profile and lipid peroxides in dairy cows with clinical mastitis. Materials and Methods: Twelve cases of clinical mastitis in cross-bred cows were selected based on physical examination of udder and milk, California Mastitis Test (CMT, Somatic Cell Count (SCC and confirmation by bacteriological examination of milk and requisite biochemical tests. Twelve lactating cows showing negative CMT reaction and SCC <2x105 cells/ml were considered as healthy control. Antioxidant parameters measured in blood were superoxide dismutase (SOD, catalase activities and reduced glutathione (GSH concentration. Erythrocytic lipid peroxidation (LPO was measured in terms of malondialdehyde (MDA production. Results: Significant (P<0.05 decrease in blood SOD and catalase activities, GSH concentration and an increase in erythrocytic lipid peroxides was observed in cows with clinical mastitis. Conclusion: It is concluded that there is a compromise in antioxidant defense of the body in dairy cows with clinical mastitis resulting in oxidative damage, therefore, necessitate the use of antioxidants and other protective compounds along with conventional therapy for mastitis control. [Vet World 2013; 6(5.000: 271-273

  6. Mild cognitive impairment: Profile of a cohort from a private sector memory clinic

    Directory of Open Access Journals (Sweden)

    Srikanth Srinivasan

    2014-01-01

    Full Text Available Background: Private hospital memory clinics might see a different clientele than university or academic institutes due to referral biases. Objective: To characterize the profile of patients with mild cognitive impairment (MCI from a private sector memory clinic. Materials and Methods: MCI was diagnosed according to revised clinical criteria of Petersen et al. For a subset of patients with MCI medial temporal atrophy and cerebral small vessel disease (white matter lesions and lacunes were rated on magnetic resonance imaging (MRI scans and analyzed for their contribution towards cognitive impairment. Results: Subjects with MCI formed one-third (113/371 of this memory clinic sample from a private hospital. MCI could be effectively diagnosed and subtyped using a brief cognitive scale (Concise Cognitive Test (CONCOG. The amnestic MCI (single and multiple domains subtype comprised the majority of cases with MCI. In a subsample of 33 patients, lacunar infarcts were more common than white matter lesions and hippocampal atrophy and were inversely associated with verbal fluency. Conclusions: MCI may be more commonly encountered in private hospital settings probably due to early referrals. It is possible to diagnose and subtype MCI using a brief cognitive instrument such as the CONCOG. In this sample, lacunar infarcts were more commonly encountered than medial temporal atrophy in such patients.

  7. Clinically available RNA profiling tests of prostate tumors: utility and comparison

    Directory of Open Access Journals (Sweden)

    Rong Na

    2016-01-01

    Full Text Available In the postscreening era, physicians are in need of methods to discriminate aggressive from nonaggressive prostate cancer (PCa to reduce overdiagnosis and overtreatment. However, studies have shown that prognoses (e.g., progression and mortality differ even among individuals with similar clinical and pathological characteristics. Existing risk classifiers (TMN grading system, Gleason score, etc. are not accurately enough to represent the biological features of PCa. Using new genomic technologies, novel biomarkers and classifiers have been developed and shown to add value to clinical or pathological risk factors for predicting aggressive disease. Among them, RNA testing (gene expression analysis is useful because it can not only reflect genetic variations but also reflect epigenetic regulations. Commercially available RNA profiling tests (Oncotype Dx, Prolaris, and Decipher have demonstrated strong abilities to discriminate PCa with poor prognosis from less aggressive diseases. For instance, these RNA profiling tests can predict disease progression in active surveillance patients or early recurrence after radical treatments. These tests may offer more dependable methods for PCa prognosis prediction to make more accurate and personal medical decisions.

  8. Attention-deficit/Hyperactivity Disorder in Children: Clinical Profile and Co-morbidity

    Science.gov (United States)

    Venkatesh, C.; Ravikumar, T.; Andal, A.; Virudhagirinathan, B. S.

    2012-01-01

    Background: To study the clinical profile and co-morbidity in Indian children with attention-deficit/hyperactivity disorder (ADHD). Materials and Methods: A prospective analytical study of 2 years duration at the Child Guidance Clinic of a pediatric tertiary care hospital in a south Indian city using Diagnostic and statistical manual of Mental Disorders-1V based questionnaires. Results: Of the 251 referrals, 51 (20.3%) children met the inclusion criteria for the diagnosis of ADHD. M:F ratio was 6.3:1. The mean age was 5.7 years. A majority of the children belonged to middle and lower socio-economic class and were first-born children. Most children were brought up in nuclear families. History of delayed speech and language development was commonly seen in these children. Combined type of ADHD was the most common type. At least one co-morbid diagnosis was seen in 86.3% of children, and learning disability was the most common co-morbid diagnosis. The mean IQ was 90 (SD±12). Conclusion: Early markers of cognitive dysfunction like delayed speech, language and social and adaptive development may be a pointer towards the diagnosis of ADHD in children. Knowledge about their sociodemographic profile and other co-morbid conditions that are associated with ADHD is necessary to fully understand the magnitude of the problem and to plan effective therapy for them. PMID:22661805

  9. Attention-deficit/Hyperactivity Disorder in Children: Clinical Profile and Co-morbidity

    Directory of Open Access Journals (Sweden)

    C Venkatesh

    2012-01-01

    Full Text Available Background: To study the clinical profile and co-morbidity in Indian children with attention-deficit/hyperactivity disorder (ADHD. Materials and Methods: A prospective analytical study of 2 years duration at the Child Guidance Clinic of a pediatric tertiary care hospital in a south Indian city using Diagnostic and statistical manual of Mental Disorders-1V based questionnaires. Results: Of the 251 referrals, 51 (20.3% children met the inclusion criteria for the diagnosis of ADHD. M:F ratio was 6.3:1. The mean age was 5.7 years. A majority of the children belonged to middle and lower socio-economic class and were first-born children. Most children were brought up in nuclear families. History of delayed speech and language development was commonly seen in these children. Combined type of ADHD was the most common type. At least one co-morbid diagnosis was seen in 86.3% of children, and learning disability was the most common co-morbid diagnosis. The mean IQ was 90 (SD±12. Conclusion: Early markers of cognitive dysfunction like delayed speech, language and social and adaptive development may be a pointer towards the diagnosis of ADHD in children. Knowledge about their sociodemographic profile and other co-morbid conditions that are associated with ADHD is necessary to fully understand the magnitude of the problem and to plan effective therapy for them.

  10. Clinically available RNA profiling tests of prostate tumors: utility and comparison

    Science.gov (United States)

    Na, Rong; Wu, Yishuo; Ding, Qiang; Xu, Jianfeng

    2016-01-01

    In the postscreening era, physicians are in need of methods to discriminate aggressive from nonaggressive prostate cancer (PCa) to reduce overdiagnosis and overtreatment. However, studies have shown that prognoses (e.g., progression and mortality) differ even among individuals with similar clinical and pathological characteristics. Existing risk classifiers (TMN grading system, Gleason score, etc.) are not accurately enough to represent the biological features of PCa. Using new genomic technologies, novel biomarkers and classifiers have been developed and shown to add value to clinical or pathological risk factors for predicting aggressive disease. Among them, RNA testing (gene expression analysis) is useful because it can not only reflect genetic variations but also reflect epigenetic regulations. Commercially available RNA profiling tests (Oncotype Dx, Prolaris, and Decipher) have demonstrated strong abilities to discriminate PCa with poor prognosis from less aggressive diseases. For instance, these RNA profiling tests can predict disease progression in active surveillance patients or early recurrence after radical treatments. These tests may offer more dependable methods for PCa prognosis prediction to make more accurate and personal medical decisions. PMID:26975490

  11. Phenotypic and molecular characterization of clinically isolated Escherichia coli

    Directory of Open Access Journals (Sweden)

    Vaishnavi Chetana

    2010-07-01

    Full Text Available All diarrheagenic Escherichia coli carry at least one virulence-related property. Stool samples from 244 patients having acute or persistent diarrhea received after the exclusion of routine enteropathogens were investigated. Purely or predominantly isolated E. coli (n = 100 were subjected to serotyping, of which only 25 were typable. They belonged to 14 different O-serogroups comprising 5 O153, 4 O102, 3 O25, 2 each of O130 and O169, and 1 each of O1, O8, O15, O37, O86, O101, O127, O143, and O160. The typable E. coli isolates along with 5 other untypable isolates were investigated for molecular markers, such as intimin (eae, enterohemolysin (EhlyA, a-hemolysin, heat-labile enterotoxins (LT, heat-stable enterotoxins (STa, verotoxins (VT1 and VT2, invasivity (ial, enteroaggregative E. coli (EAEC gene (EAGG, and enterotoxin (EAST. Two of the isolates (O153 and O86 were positive for enterohemolysin phenotypically and 5 for β-hemolysin both phenotypically and genotypically. Interestingly, 16.6% of the randomly isolated E. coli were O153, a serogroup common in cattle, and 10% belonged to EAEC pathotype of which two-thirds had the EAST gene, which is quite frequent in these strains. Additionally, there was one strain (O153 that was positive for EAST only. Between the two 0130:H6 strains isolated, one belonged to EAEC serogroup. None of the E. coli isolated were positive for verotoxins, eae, LT1, STa, and ial. Data obtained emphasize the need for additional research into the role of eae gene and other putative factors affecting the virulence of diarrheagenic E. coli in India.

  12. Natural incidence of aflatoxins, mycological profile and molecular characterization of aflatoxigenic strains in chickpea flour

    International Nuclear Information System (INIS)

    The mycological profile of retail chickpea flour (locall called Baisan), sold in the markets in the Rawalpindi district was studied. All the samples were tested for the contamination with aflatoxins. A total of 13 fungal species isolated from the flour and out of which, Aspergillus flavus was recorded the most common species (100%), followed by Rhizopus oryzea (50%), Aspergillus niger (40%), Penicilium digitatum (30%), Cladosporium cladosporoides, Fusarium oxysporium, Mucor recemosus, M. petrinsularis and Rhizopus arrhizus (20% each), Aspergillus oryzea, Botritus cinerea, Mucor circineloides and Penicillium sp. (10% each). Aflatoxin B1 was found in only 20% of the samples ranging from 3.03-4.24ppb. The molecular characterization was carried out by using PCR using simple sequence repeats (SSR) primers. The SSR amplification pattern clearly showed the genetic variability among the 10 strains of A. flavus. A dendrogram was generated through MVSP software program. Genotype AF04 was most diverse among all genotypes. The similarity value was ranged between 0.538 (53.8%)-0.938 (93.8%). (author)

  13. Integrative Molecular Profiling Reveals Asparagine Synthetase Is a Target in Castration-Resistant Prostate Cancer

    Science.gov (United States)

    Sircar, Kanishka; Huang, Heng; Hu, Limei; Cogdell, David; Dhillon, Jasreman; Tzelepi, Vassiliki; Efstathiou, Eleni; Koumakpayi, Ismaël H.; Saad, Fred; Luo, Dijun; Bismar, Tarek A.; Aparicio, Ana; Troncoso, Patricia; Navone, Nora; Zhang, Wei

    2013-01-01

    The identification of new and effective therapeutic targets for the lethal, castration-resistant stage of prostate cancer (CRPC) has been challenging because of both the paucity of adequate frozen tissues and a lack of integrated molecular analysis. Therefore, in this study, we performed a genome-wide analysis of DNA copy number alterations from 34 unique surgical CRPC specimens and 5 xenografts, with matched transcriptomic profiling of 25 specimens. An integrated analysis of these data revealed that the asparagine synthetase (ASNS) gene showed a gain in copy number and was overexpressed at the transcript level. The overexpression of ASNS was validated by analyzing other public CRPC data sets. ASNS protein expression, as detected by reverse-phase protein lysate array, was tightly correlated with gene copy number. In addition, ASNS protein expression, as determined by IHC analysis, was associated with progression to a therapy-resistant disease state in TMAs that included 77 castration-resistant and 40 untreated prostate cancer patient samples. Knockdown of ASNS by small-interfering RNAs in asparagine-deprived media led to growth inhibition in both androgen-responsive (ie, LNCaP) and castration-resistant (ie, C4-2B) prostate cancer cell lines and in cells isolated from a CRPC xenograft (ie, MDA PCa 180-30). Together, our results suggest that ASNS is up-regulated in cases of CRPC and that depletion of asparagine using ASNS inhibitors will be a novel strategy for targeting CRPC cells. PMID:22245216

  14. Molecular profile of sensitization in subjects with short occupational exposure to latex

    Directory of Open Access Journals (Sweden)

    Monica Lamberti

    2015-10-01

    Full Text Available Objectives: We examined the prevalence of latex allergy in subjects with occupational exposure to latex allergens for less than 5 years, determining the disease spectrum in symptomatic workers. We identified the most frequent molecular allergens by Immuno- CAP (ICAP, correlating the findings with skin prick test (SPT results. Material and Methods: Seven hundred twenty-three healthcare students using latex gloves on a regular basis were invited to participate in a baseline questionnaire screening. An ICAP serum test was performed only when a possible latex allergy was indicated by the questionnaire. Results: The total number of participants responding to the baseline survey was 619. Glove-related symptoms were indicated by 4% (N = 25 of the students. The most common symptom was contact dermatitis (N = 18, 72%. In 12 subjects, ICAP revealed a real sensitization to latex, with a recombinant latex allergen profile showing a high frequency for rHev b 6.01 specific immunoglobulin E (sIgE (N = 9, 67%. In these individuals, skin symptoms were more prevalent than other types (88%. Conclusions: The combined positivity for rHev b 6.01, rHev 8 and rHev b 5 determined by ICAP identified 92% of latex-allergic subjects with short-term exposure to latex.

  15. Reaction Profiles and Molecular Dynamics Simulations of Cyanide Radical Reactions Relevant to Titan's Atmosphere

    Science.gov (United States)

    Trinidad Pérez-Rivera, Danilo; Romani, Paul N.; Lopez-Encarnacion, Juan Manuel

    2016-10-01

    Titan's atmosphere is arguably the atmosphere of greatest interest that we have an abundance of data for from both ground based and spacecraft observations. As we have learned more about Titan's atmospheric composition, the presence of pre-biotic molecules in its atmosphere has generated more and more fascination about the photochemical process and pathways it its atmosphere. Our computational laboratory has been extensively working throughout the past year characterizing nitrile synthesis reactions, making significant progress on the energetics and dynamics of the reactions of .CN with the hydrocarbons acetylene (C2H2), propylene (CH3CCH), and benzene (C6H6), developing a clear picture of the mechanistic aspects through which these three reactions proceed. Specifically, first principles calculations of the reaction profiles and molecular dynamics studies for gas-phase reactions of .CN and C2H2, .CN and CH3CCH, and .CN and C6H6 have been carried out. A very accurate determination of potential energy surfaces of these reactions will allow us to compute the reaction rates which are indispensable for photochemical modeling of Titan's atmosphere.The work at University of Puerto Rico at Cayey was supported by Puerto Rico NASA EPSCoR IDEAS-ER program (2015-2016) and DTPR was sponsored by the Puerto Rico NASA Space Grant Consortium Fellowship. *E-mail: juan.lopez15@upr.edu

  16. Diversity of Bipolaris species in clinical samples in the United States and their antifungal susceptibility profiles.

    Science.gov (United States)

    da Cunha, K C; Sutton, D A; Fothergill, A W; Cano, J; Gené, J; Madrid, H; De Hoog, S; Crous, P W; Guarro, J

    2012-12-01

    A set of 104 isolates from human clinical samples from the United States, morphologically compatible with Bipolaris, were morphologically and molecularly identified through the sequence analysis of the internal transcribed space (ITS) region of the nuclear ribosomal DNA (rDNA). The predominant species was Bipolaris spicifera (67.3%), followed by B. hawaiiensis (18.2%), B. cynodontis (8.6%), B. micropus (2.9%), B. australiensis (2%), and B. setariae (1%). Bipolaris cynodontis, B. micropus, and B. setariae represent new records from clinical samples. The most common anatomical sites where isolates were recovered were the nasal region (30.7%), skin (19.2%), lungs (14.4%), and eyes (12.5%). The antifungal susceptibilities of 5 species of Bipolaris to 9 drugs are provided. With the exception of fluconazole and flucytosine, the antifungals tested showed good activity. PMID:23052310

  17. NON-RESOLVING PNEUMONIA AETIOLOGY AND CLINICAL PROFILE: A PROSPECTIVE STUDY

    Directory of Open Access Journals (Sweden)

    Binuraj

    2016-03-01

    Full Text Available BACKGROUND Pneumonia is defined as the inflammation and consolidation of the lung tissue due to an infectious agent. In as many as half of cases, the pathogen remains unidentified which greatly hampers the evaluation of slowly resolving or non-resolving pneumonia. OBJECTIVE The main objective is to evaluate the aetiology and clinical profile of non-resolving pneumonia in a tertiary care center and to study the outcome of treatment of non-resolving pneumonia. DESIGN AND SETTING A prospective, observational study was carried out in the department of pulmonary medicine of a 700 bedded tertiary care teaching hospital, Kerala. MATERIALS AND METHODS The patients who were diagnosed as non-resolving pneumonia were included in the study. Various investigations were done on patients to identify the aetiology and clinical profile of their pneumonia which includes sputum gram stain, culture and sensitivity for bacterial infections, AFB culture, fungal culture, chest X-ray, CT thorax, fibrotic bronchoscopy (For selected patients only and sputum cytology for malignant cells. STATISTICAL METHODS USED Descriptive statistical analysis was done with help of ‘Graph pad prism’. RESULTS With good clinical interpretations and appropriate treatment, about 31.8% of patients had good clinical improvement and complete chest X-ray clearance after 2 months of follow up where as 36.2% of study subjects had good clinical improvement with incomplete chest X-ray clearance. Majority of this group includes patients who were put on anti-tubercular treatment based on careful interpretation of chest X-ray findings of tuberculosis, Mantoux test and sputum AFB culture results. This implies the importance of early diagnosis of treatable diseases like tuberculosis in our population. Out of the total cases 21.2% of patients had poor clinical outcome whereas 4.4% patients were grabbed by death. CONCLUSION Tuberculosis was the commonest cause of non-resolving pneumonia followed by

  18. Clinical profile of parkinsonian disorders in the tropics: Experience at Kano, northwestern Nigeria

    Directory of Open Access Journals (Sweden)

    Owolabi Lukman Femi

    2012-01-01

    Full Text Available Background: No data exists on Parkinson′s disease (PD and secondary Parkinsonism in Northwestern Nigeria. This study was designed to create a database, document the clinical profile of PD in Kano, northwestern Nigerian, and compare this to prior observations within and outside Nigeria. Materials and Methods: A database was documented on prospective patients presenting consecutively to the Neurology out-patients clinic of the two tertiary health facilities in Kano northwestern Nigeria over a period of 4 years. Demographic and clinical data at presentation were documented for all patients. Cases were classified as PD or secondary Parkinsonism. The severity at presentation and at last visit was classified using the H and Y scale. Results: Over a period of 4 years, out 1153 a total of 96 patients comprising 74 males and 22 females were enrolled. Eighty (83.3% of them had clinically diagnosed PD while 16 (16.7% had clinical features compatible with secondary Parkinsonism. The mean age at onset of symptoms in the PD patients (mean 58.2 ± 6.72 yrs was more than in secondary Parkinsonism (mean 51.4 ± 10.04 and P = 0.001. There was male preponderance in both idiopathic Parkinsonism (PD (m:f = 3.2:1 and secondary Parkinsonism (m:f = 4.3:1. Out of the patients with secondary Parkinsonism, 10 (62.5% and 5 (31.3% had vascular Parkinsonism and drug-induced Parkinsonism, respectively. Duration of symptoms prior to presentation ranged between 3 months and 16 years. The mean (SD time interval from the onset of motor symptoms to diagnosis of PD was 3.6 ± 3.4 yrs and time interval for men and women (male 3.8 ± 3.7; female 2.8 ± 2.1; P = 0.249. Conclusions : Clinical profile of patients with PD and secondary Parkinsonism in Kano is similar to that from other populations within Nigeria and other developing countries. However, delayed presentation, less frequent family history, lower frequency of Young-onset PD as well as treatment challenges occasioned by

  19. Specific serum microRNA profile in the molecular diagnosis of Hirschsprung's disease.

    Science.gov (United States)

    Tang, Weibing; Li, Hongxing; Tang, Junwei; Wu, Wei; Qin, Jingjing; Lei, Hao; Cai, Peng; Huo, Weiwei; Li, Bo; Rehan, Virender; Xu, Xiaoqun; Geng, Qiming; Zhang, Hongwei; Xia, Yankai

    2014-08-01

    Hirschsprung's disease (HSCR), a congenital gastrointestinal disorder, is one of the most common causes of neonatal bowel obstruction. Without an early screening and diagnosis, some patients develop serious complications, such as toxic megacolon or acute enterocolitis. We sought to identify specific serum microRNAs (miRNAs) that can serve as novel early, non-invasive screening signature and then to test their specificity and sensitivity in diagnosing Hirschsprung's disease. We obtained serum samples from 95 HSCR cases and 104 matched controls. An initial screening of miRNA expression was performed through TaqMan Low Density Array. The candidate miRNAs were validated by individual reverse transcription quantitative real-time PCR arranged in the training and a two-stage validation set. Additional double-blind testing was performed in 23 patients with clinically suspected HSCR to evaluate the diagnostic value and accuracy of the serum miRNA profile in predicting HSCR. Following a multi-stage evaluation approach, five miRNAs were significantly increased in HSCR cases compared with controls. The areas under the receiver operating characteristic (ROC) curve of this five-serum miRNA signature were 0.895, 0.893 and 0.925 in training set and two validation sets, respectively. The accuracy rate of the five-miRNA profile as HSCR signature was 82.6%, which, in the double-blind testing set, was markedly higher than that of contrast enema (70%), the most commonly used test performed to diagnose HSCR. Our results indicate that a five-serum miRNA signature may be linked to HSCR, representing a potential, novel, non-invasive diagnostic approach for early screening of HSCR. PMID:24974861

  20. Clinical and microbiological profile of persistent coagulase-negative staphylococcal bacteraemia in neonates.

    Science.gov (United States)

    Dimitriou, G; Fouzas, S; Giormezis, N; Giannakopoulos, I; Tzifas, S; Foka, A; Anastassiou, D E; Spiliopoulou, I; Mantagos, S

    2011-11-01

    An atypical pattern of coagulase-negative staphylococcal (CoNS) sepsis, characterized by persistence despite aggressive antibiotic therapy, has been described in neonates cared for in neonatal intensive-care units. Our aim was to analyse the clinical, microbiological and molecular determinants of this persistent CoNS bacteraemia. Neonates with late-onset CoNS bacteraemia were studied for a 2-year period. Demographic, clinical, laboratory, microbiological and molecular data were compared between neonates with persistent (≥3 consecutive positive blood cultures) and non-persistent CoNS bacteraemia. Twenty-nine infants with persistent and 43 with non-persistent bacteraemia were identified, with no significant differences regarding demographic and clinical characteristics between the two groups. Of a total of 170 CoNS isolates, 80 showed biofilm production (54 persistent and 26 non-persistent; p 0.013), whereas 127 were positive for the icaA and icaD genes (74 persistent and 53 non-persistent; p 0.598). Sixty ica-positive isolates did not produce slime, whereas 13 ica-negative isolates showed biofilm production. Endotracheal intubation and the presence of central vascular catheters were significant risk factors for persistent bacteraemia, but, in a logistic regression model, only biofilm production was significantly related to the persistent form of the disease (p 0.005). In this study, persistent CoNS sepsis in neonates requiring intensive care was not related to most of the known clinical risk factors, and it was associated with severe thrombocytopenia. Isolates associated with persistent bacteraemia were more likely to produce biofilm, independently of the presence of the ica operon. PMID:21463392

  1. Basic research and clinical application of optical molecular imaging in breast cancer

    International Nuclear Information System (INIS)

    As a rapidly developing biomedical imaging technology,in vivo optical molecular imaging has been widely applied in various research fields owing to its unique real-time, quantitative and noninvasive characteristics. The applications of in vivo optical imaging technology in the basic and clinical research of breast cancer were reviewed, including detection of distant metastasis,tumor apoptosis, cell cycle, hypoxia and angiogenesis, ER-mediated molecular pathway, breast cancer stem cells, early diagnosis, sentinel node biopsy, evaluation of drug efficacy and detection of human epidermal growth factor receptor-2 (HER-2) expression. They all seem to have a promising potential in in vivo optical molecular imaging. (authors)

  2. Clinical Features and Drug-Resistance Profile of Urinary Tuberculosis in South-Western China: A Cross-sectional Study.

    Science.gov (United States)

    Ye, Yuanxin; Hu, Xuejiao; Shi, Yunying; Zhou, Juan; Zhou, Yi; Song, Xingbo; Xie, Yi; Lu, Xiaojun; Wang, Lanlan; Ying, Binwu; Chen, Xuerong

    2016-05-01

    To investigate the epidemiology, clinical features, and drug-resistance profile of urinary tuberculosis (UTB) in south-western China to improve UTB diagnostics.After the screening of 1036 cases of suspected UTB, 193 patients with UTB were enrolled during 2009 to 2014. Urine samples were collected for routine urinalysis, smear, tuberculosis DNA (TB-DNA) detection, and drug-resistant analysis, whereas blood samples were collected for erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and renal function evaluation. Clinical features (such as symptoms and outcome) and imageology results (such as B ultrasonic, computerized tomography, intravenous pyelography, and renography) were also collected and analyzed to investigate the epidemiology, clinical features, and drug-resistance profile.The most common presenting symptoms were urinary irritation (61.1%) and lumbago (49.2%). High proportions of microscopic hematuria (63.2%) and microscopic proteinuria (45.6%) were also observed. The positive rate for TB-DNA was 66.3%. The positive rate for culture was 13.1% and for smear it was 9.8%. The abnormal outcome rates of the computerized tomography, ultrasonography, intravenous pyelography, and the nephrogram were 76.9%, 70.1%, 29.8%, and 37.0%, respectively. The total rate of drug-resistant TB (resistant to at least 1 drug) was 39.7%, of which 20.7% was multidrug-resistance TB. The most prevalent mutation sites were katG S315T1, rpoB S531L, and gyrA D94G.We observed a serious epidemic of drug-resistant UTB and a substantial number of new UTB cases with multidrug resistance TB. Molecular diagnostics is crucial in the definite diagnosis of UTB, and our finding is a supplement and further confirmation of polymerase chain reaction usage for TB diagnosis. We recommend real-time polymerase chain reaction for TB-DNA identification instead of culture, and GenoType tests (MTBDRplus and MTBDRsl assay) for drug resistance as routine assays for patients with suspected UTB. PMID

  3. Platelet profile is associated with clinical complications in patients with vivax and falciparum malaria in Colombia

    Directory of Open Access Journals (Sweden)

    Edgar Leonardo Martínez-Salazar

    2014-06-01

    Full Text Available Introduction Thrombocytopenia is a common complication in malaria patients. The relationship between abnormal platelet profile and clinical status in malaria patients is unclear. In low and unstable endemic regions where vivax malaria predominates, the hematologic profiles of malaria patients and their clinical utility are poorly understood. The aim of this study was to characterize the thrombograms of malaria patients from Colombia, where Plasmodium vivax infection is common, and to explore the relationship between thrombograms and clinical status. Methods Eight hundred sixty-two malaria patients were enrolled, including 533 (61.8% patients infected with Plasmodium falciparum, 311 (36.1% patients infected with Plasmodium vivax and 18 (2.1% patients with mixed infections. Results The most frequently observed changes were low platelet count (PC and high platelet distribution width (PDW, which were observed in 65% of patients; thrombocytopenia with <50,000 platelets/µL was identified in 11% of patients. Patients with complications had lower PC and plateletcrit (PT and higher PDW values. A higher risk of thrombocytopenia was identified in patients with severe anemia, neurologic complications, pulmonary complications, liver dysfunction, renal impairment and severe hypoglycemia. The presence of thrombocytopenia (<150,000 platelets/µL was associated with a higher probability of liver dysfunction. Conclusions Young age, longer duration of illness and higher parasitemia are associated with severe thrombocytopenia. Our study showed that thrombocytopenia is related to malaria complications, especially liver dysfunction. High PDW in patients with severe malaria may explain the mechanisms of thrombocytopenia that is common in this group of patients.

  4. Clinical and Audio Vestibular Profile of Meniere's Disease in a Tertiary Care Centre in India.

    Science.gov (United States)

    Selvakumar, Paul; Balraj, Achamma; Kurien, Regi; Krishnan, Thenmozhi

    2012-12-01

    The aims of this study are to determine the frequency of patients presenting with Meniere's Disease(MD) in an Indian setting, using the American Academy of Otolaryngology-Head and Neck Surgery (AAO) diagnostic criteria, and to describe the clinical and audio vestibular profiles of these patients. The study was based on prospective case series design in the settings of a tertiary referral hospital. The study included all consecutive patients aged between 5 and 75 years presenting with the history of hearing loss, vertigo, tinnitus and or aural fullness as participants, satisfying inclusion and exclusion criteria for MD (AAO 1995) recruited over a 12 month period. Main outcome measures comprised the evaluation of epidemiological profile, clinical features, and results of audio vestibular investigations like Pure Tone Audiometry with and without glycerol, Impedance Audiometry, Electrocochleography (ECohG), Distortion Product Otoacoustic Emission and Electronystagmography (ENG). The results of the study are as follows: The frequency of MD was 15.6%, being commoner in males than females (2.6:1) and occurring more in the age group 40-49  years among males and 30-39 years among females. High frequency tinnitus was commoner than low frequency tinnitus. Extra tympanic ECohG had a positive predictive value of 76% for endolymphatic hydrops. ENG was useful for demonstrating canal paresis pattern of nystagmus in 61%. Indian patients with MD commonly present to tertiary care at the functional level scale of 3. The results of this study revealed that the frequency of MD is not as low in the Indian ENT setting as earlier believed. There is a high chance of missing cases in the routine ENT outpatient clinic setting unless a structured proforma incorporating the AAO 1995 diagnostic criteria is used. PMID:24294577

  5. Neurofibromatosis type 2 (NF2: A clinical and molecular review

    Directory of Open Access Journals (Sweden)

    Evans D Gareth R

    2009-06-01

    Full Text Available Abstract Neurofibromatosis type 2 (NF2 is a tumour-prone disorder characterised by the development of multiple schwannomas and meningiomas. Prevalence (initially estimated at 1: 200,000 is around 1 in 60,000. Affected individuals inevitably develop schwannomas, typically affecting both vestibular nerves and leading to hearing loss and deafness. The majority of patients present with hearing loss, which is usually unilateral at onset and may be accompanied or preceded by tinnitus. Vestibular schwannomas may also cause dizziness or imbalance as a first symptom. Nausea, vomiting or true vertigo are rare symptoms, except in late-stage disease. The other main tumours are schwannomas of the other cranial, spinal and peripheral nerves; meningiomas both intracranial (including optic nerve meningiomas and intraspinal, and some low-grade central nervous system malignancies (ependymomas. Ophthalmic features are also prominent and include reduced visual acuity and cataract. About 70% of NF2 patients have skin tumours (intracutaneous plaque-like lesions or more deep-seated subcutaneous nodular tumours. Neurofibromatosis type 2 is a dominantly inherited tumour predisposition syndrome caused by mutations in the NF2 gene on chromosome 22. More than 50% of patients represent new mutations and as many as one-third are mosaic for the underlying disease-causing mutation. Although truncating mutations (nonsense and frameshifts are the most frequent germline event and cause the most severe disease, single and multiple exon deletions are common. A strategy for detection of the latter is vital for a sensitive analysis. Diagnosis is based on clinical and neuroimaging studies. Presymptomatic genetic testing is an integral part of the management of NF2 families. Prenatal diagnosis and pre-implantation genetic diagnosis is possible. The main differential diagnosis of NF2 is schwannomatosis. NF2 represents a difficult management problem with most patients facing substantial

  6. Analysis of pulsotypes of salmonella typhi isolates and their clinical profiles in typhoid fever patients

    Directory of Open Access Journals (Sweden)

    Retno K. Soemanto

    2003-03-01

    Full Text Available A study of genotyping (pulsotyping of Salmonella typhi (S. typhi isolates using pulse-field gel electrophoresis (PFGE methods was performed to examine their genetic diversity, and relationship between genetic characteristics and clinical outcomes.  Sixty-six S. typhi isolates obtained from sporadic hospitalized typhoid fever cases were used in this study. Four isolates were found identical and the dendogram constructed showed 33 pulsotypes in which 13 of them can be divided into 30 subtypes. Diversity among them were high as shown by the Dice coefficients that ranged from 0.486 to 1.000. Cluster analysis showed 2 main clusters with 65% degree of similarity, suggested that they were not originated from one clone. Further, at 90% degree of similarity, 9 clusters containing at least 3 isolates were determined to explore any possible existence of relationship between genetic profile and particular clinical outcomes. Clinical manifestations ranged from mild to severe were in fact distributed diversely among these clusters. Although the clinical data obtained were incomplete, 2 out of 4 patients infected by the S. typhi belonged to cluster 1 showed an elevation of total bilirubin, whereas it was not found in 19 other patients distributed in other 8 clusters. Even though specific clinical manifestations were apparently not found to relate with particular clusters of genotypes, S. typhi isolates grouped in cluster 1 seemed to show trophism to hepatobiliary system. (Med J Indones 2003; 12: 13-20 Keywords: S. typhi, typhoid fever, Pulsed-field Gel electrophoresis (PFGE

  7. Clinical Significance of Auditory Target P300 Subcomponents in Psychosis: Differential Diagnosis, Symptom Profiles, and Course

    Science.gov (United States)

    Perlman, Greg; Foti, Dan; Jackson, Felicia; Kotov, Roman; Constantino, Eduardo; Hajcak, Greg

    2015-01-01

    Background Reduced auditory target P300 amplitude is a leading biomarker for psychotic disorders, although its relevance for differential diagnosis and link to specific clinical features (symptom profiles, functional impairment, and course) is unclear. This study aims to clarify the clinical significance of auditory target P300 using concurrent and retrospective clinical data from a longitudinal cohort with psychosis. Methods 92 cases from an epidemiological study of first-admission psychosis were assessed using an auditory oddball paradigm at 15-year follow-up along with 44 never-psychotic adults. Subcomponents of auditory target P300 amplitude (i.e., a central positive P3a, a parietal positive P3b, and a frontal negative slow wave) were isolated using temporal-spatial principal components analysis. Results P3a amplitude was blunted across psychotic disorders relative to non-psychotic adults. P3b amplitude was reduced in schizophrenia specifically, including cases initially misclassified at baseline. The frontal negative slow wave did not distinguish among groups. P3b amplitude reduction was associated with several clinical features at the concurrent assessment, as well as previous time points, including recovery from psychosis even 5 years earlier and functioning even 15 years earlier. Conclusions Auditory target P300 amplitude yields both a schizophrenia-specific component (i.e., P3b) and a transdiagnostic psychosis component (i.e., P3a). The P3b component may also shed light on prognosis, real-world functioning, and course, as well as help to reduce misdiagnosis of psychotic disorders. Prospective studies are needed to test whether P3b tracks or predicts clinical status. PMID:25934167

  8. DNA COPY PROFILE IN NASOPHARYNGEAL CARCINOMA AND ITS CORRELATION WITH CLINICAL STAGING

    Institute of Scientific and Technical Information of China (English)

    鄢践; 方嬿; 梁启万; 曾益新

    2001-01-01

    To detect genetic alterations in nasopharyngeal carcinoma (NPC) in Cantonese, the population with the highest incidence of NPC, and to correlate the findings with clinical staging. Methods: Comparative genomic hybridization (CGH) was performed on 35 primary nasopharyngeal carcinomas and a nonparametric χ2 test was used to analyze relationship between chromosome changes and clinical staging. Results: The identified common chromosomal alterations in NPC included gain of chromosomes 12q (21 cases, 60%), 4q (19cases, 43%), 3q (18 cases, 51%), 1q (15 cases, 43%),8q (14 cases, 40%), and 2q (12 cases, 30%). The most frequently detected loss of chromosomal materials involved chromosome 1p (24 cases, 69%), chromosome 3p (21 cases, 60%), 11q (20 cases, 57%), 14q (18 cases, 51%), 16q (14 cases, 40%), 13(12 cases, 34%), and 9p(11 cases, 31%). The high frequency (>50%) 4q gain and 1p loss were novel findings. Compared by nonparametric χ2 test, gains on 12q and 8q were found mainly in stages Ⅲ/Ⅳ and there were significant differences between two clinical stage groups ( stagesⅠ/Ⅱvs stages Ⅲ/Ⅳ). Conclusions: Current analysis has revealed a comprehensive profile of the chromosomal regions showing DNA copy number changes, which may harbor oncogenes or tumor suppressor genes involved in the development of primary NPC.

  9. Sociodemographic and clinical profile of children with congenital heart disease assisted at a hospital institution

    Directory of Open Access Journals (Sweden)

    Mirna Albuquerque Frota

    2014-06-01

    Full Text Available Objective: To characterize the sociodemographic and clinical profile of children with congenital heart disease assisted at a hospital institution. Methods: A descriptive, crosssectional study conducted in the pediatric cardiology outpatient clinic of a hospital in Fortaleza, CE, Brazil, in the period from March to August 2012. It comprised a nonrandom convenience sample of 80 parents of children with heart disease aged 5 to 12 years. Information was obtained from primary data of medical records and through questionnaires covering the parent’s sociodemographic characteristics, family data and the children’s clinical aspects. Results: Regarding socioeconomic data, 77 (96.2% caregivers were female, 50 (62.5% were married or in a stable relationship, 39 (48.7% had 10-12 years of formal education, and 69 (82.6% reported a household income between 1 and 2 minimum wages. In the sample of children studied, 43 (53.8% were female. The median age of the children was 8.4 years, ranging from 5-13 years. As to the age at the heart disease diagnosis, 44 (55% occurred under the age of 6 months, regardless of the type of cardiopathy. It was detected that 19 (23.75% were related to the disease. Conclusion: Children’s caregivers were predominantly their mothers, with low income and satisfactory schooling. Early diagnosis was predominant, mainly among the children with cyanotic cardiopathy. doi:10.5020/18061230.2014.p239

  10. Polymorphism in clinical immunology – From HLA typing to immunogenetic profiling

    Directory of Open Access Journals (Sweden)

    Wang Ena

    2003-11-01

    Full Text Available Abstract The pathology of humans, in contrast to that of inbred laboratory animals faces the challenge of diversity addressed in genetic terms as polymorphism. Thus, unsurprisingly, treatment modalities that successfully can be applied to carefully-selected pre-clinical models only sporadically succeed in the clinical arena. Indeed, pre-fabricated experimental models purposefully avoid the basic essence of human pathology: the uncontrollable complexity of disease heterogeneity and the intrinsic diversity of human beings. Far from pontificating on this obvious point, this review presents emerging evidence that the study of complex system such as the cytokine network is further complicated by inter-individual differences dictated by increasingly recognized polymorphisms. Polymorphism appears widespread among genes of the immune system possibly resulting from an evolutionary adaptation of the organism facing an ever evolving environment. We will refer to this high variability of immune-related genes as immune polymorphism. In this review we will briefly highlight the possible clinical relevance of immune polymorphism and suggest a change in the approach to the study of human pathology, from the targeted study of individual systems to a broader view of the organism as a whole through immunogenetic profiling.

  11. Microbiological Profile of Adenoid Hypertrophy Correlates to Clinical Diagnosis in Children

    Directory of Open Access Journals (Sweden)

    Anita Szalmás

    2013-01-01

    Full Text Available Objective. Adenoid hypertrophy is a common condition in childhood, which may be associated with recurring acute otitis media (RAOM, otitis media with effusion (OME, and obstructive sleep apnea syndrome (OSAS. These different clinical characteristics have some clinical overlap; however, they might be explained by distinct immunologic and infectious profiles and result in various histopathologic findings of adenoid specimens. Methods. A total of 59 children with adenoid hypertrophy undergoing adenoidectomy were studied. Three series of identical adenoid specimens were processed to hematoxylin-eosin (H.E. and Gram staining and to respiratory virus specific real-time PCR, respectively. Results. According to the clinical characteristics, patients were recruited into three groups: RAOM (. Bacterial biofilms were detected in 21 cases, while at least one of the studied respiratory viruses was detected in 52 specimens. RAOM cases were significantly associated with biofilm existence (. In contrast, OME group was characterized by the absence of bacterial biofilm and by normal mucosa. Showing a statistically significant correlation, all OME cases were positive for human bocavirus (HBoV, . Conclusions. Bacterial biofilms might contribute to the damage of respiratory epithelium and recurring acute infections resulting in RAOM. In OME cases persisting respiratory viruses, mainly HBoV, can cause subsequent lymphoid hyperplasia leading to ventilation disorders and impaired immunoreactivity of the middle ear cleft.

  12. The Clinical Use of Genomic Profiling to Distinguish Intrapulmonary Metastases From Synchronous Primaries in Non-Small-Cell Lung Cancer: A Mini-Review.

    Science.gov (United States)

    Klempner, Samuel J; Ou, Sai-Hong Ignatius; Costa, Daniel B; VanderLaan, Paul A; Sanford, Eric M; Schrock, Alexa; Gay, Laurie; Ali, Siraj M; Miller, Vincent A

    2015-09-01

    The ability to reliably distinguish synchronous primary non-small-cell lung cancer (NSCLC) from intrapulmonary metastatic spread affects staging and treatment decisions in resected NSCLC. Adjuvant therapy for early-stage NSCLC is complicated and recommendations are primarily based on older data from trials that used now-outdated staging systems. Patients found to have 2 tumors with similar morphology in the same lobe are currently staged as pathologic T3 (pT3) but such cases represent a minority of patients in adjuvant lung cancer trials. Potentially more precise than tumor morphology alone, comprehensive genomic profiling technologies have the power to discriminate whether tumors in the same lobe represent 2 separate primary lesions or localized spread of a single lesion. In addition to lineage insights, tumor profiling simultaneously provides information on actionable genomic alterations. In this review we discuss the data that support the ability of molecular technologies to distinguish synchronous primary tumors from intrapulmonary metastases and discuss the use of molecular assays as an adjunct to current staging systems. Two cases are presented to highlight the potential immediate clinical implications of comprehensive genomic profiling. PMID:25911330

  13. Relating multi-sequence longitudinal intensity profiles and clinical covariates in incident multiple sclerosis lesions.

    Science.gov (United States)

    Sweeney, Elizabeth M; Shinohara, Russell T; Dewey, Blake E; Schindler, Matthew K; Muschelli, John; Reich, Daniel S; Crainiceanu, Ciprian M; Eloyan, Ani

    2016-01-01

    The formation of multiple sclerosis (MS) lesions is a complex process involving inflammation, tissue damage, and tissue repair - all of which are visible on structural magnetic resonance imaging (MRI) and potentially modifiable by pharmacological therapy. In this paper, we introduce two statistical models for relating voxel-level, longitudinal, multi-sequence structural MRI intensities within MS lesions to clinical information and therapeutic interventions: (1) a principal component analysis (PCA) and regression model and (2) function-on-scalar regression models. To do so, we first characterize the post-lesion incidence repair process on longitudinal, multi-sequence structural MRI from 34 MS patients as voxel-level intensity profiles. For the PCA regression model, we perform PCA on the intensity profiles to develop a voxel-level biomarker for identifying slow and persistent, long-term intensity changes within lesion tissue voxels. The proposed biomarker's ability to identify such effects is validated by two experienced clinicians (a neuroradiologist and a neurologist). On a scale of 1 to 4, with 4 being the highest quality, the neuroradiologist gave the score on the first PC a median quality rating of 4 (95% CI: [4,4]), and the neurologist gave the score a median rating of 3 (95% CI: [3,3]). We then relate the biomarker to the clinical information in a mixed model framework. Treatment with disease-modifying therapies (p < 0.01), steroids (p < 0.01), and being closer to the boundary of abnormal signal intensity (p < 0.01) are all associated with return of a voxel to an intensity value closer to that of normal-appearing tissue. The function-on-scalar regression model allows for assessment of the post-incidence time points at which the covariates are associated with the profiles. In the function-on-scalar regression, both age and distance to the boundary were found to have a statistically significant association with the lesion intensities at some time point

  14. 76 FR 18227 - Molecular and Clinical Genetics Panel of the Medical Devices Advisory Committee; Notice of...

    Science.gov (United States)

    2011-04-01

    ... in the Federal Register of February 7, 2011 (76 FR 6623). In the notice, FDA requested public comment.... Background In the Federal Register of February 7, 2011 (76 FR 6623), FDA published a notice announcing a... HUMAN SERVICES Food and Drug Administration Molecular and Clinical Genetics Panel of the Medical...

  15. Clinical and molecular delineation of the 17q21.31 microdeletion syndrome.

    NARCIS (Netherlands)

    Koolen, D.A.; Sharp, A.J.; Hurst, J.A.; Firth, H.V.; Knight, S.J.; Goldenberg, A.; Saugier-Veber, P.; Pfundt, R.P.; Vissers, L.E.L.M.; Destree, A.; Grisart, B.; Rooms, L.; Aa, N. van der; Field, M.; Hackett, A.; Bell, K.; Nowaczyk, M.J.; Mancini, G.M.; Poddighe, P.J.; Schwartz, C.E.; Rossi, E.; Gregori, M. de; Antonacci-Fulton, L.L.; McLellan, MD2nd; Garrett, J.M.; Wiechert, M.A.; Miner, T.L.; Crosby, S.; Ciccone, R.; Willatt, L.; Rauch, A.; Zenker, M.; Aradhya, S.; Manning, M.A.; Strom, T.M.; Wagenstaller, J.; Krepischi-Santos, A.C.; Vianna-Morgante, A.M.; Rosenberg, C.; Price, S.M.; Stewart, H.; Shaw-Smith, C.; Brunner, H.G.; Wilkie, A.O.; Veltman, J.A.; Zuffardi, O.; Eichler, E.E.; Vries, L.B.A. de

    2008-01-01

    BACKGROUND: The chromosome 17q21.31 microdeletion syndrome is a novel genomic disorder that has originally been identified using high resolution genome analyses in patients with unexplained mental retardation. AIM: We report the molecular and/or clinical characterisation of 22 individuals with the 1

  16. Allelic polymorphism of glucocorticoid receptor NR3C1 (GR: from molecular biology to clinical implications

    Directory of Open Access Journals (Sweden)

    Orlovsky M. A.

    2012-09-01

    Full Text Available Polymorphism of stress-related genes is a key factor determining difference in the stress reactivity and resistance among humans. Glucocorticoid receptors are important actors of stress responses. This review is focused on the molecular biology and clinical implications of glucocorticoid receptor gene polymorphism.

  17. 22q13.3 Deletion Syndrome : Clinical and Molecular Analysis Using Array CGH

    NARCIS (Netherlands)

    Dhar, S. U.; del Gaudio, D.; German, J. R.; Peters, S. U.; Ou, Z.; Bader, P. I.; Berg, J. S.; Blazo, M.; Brown, C. W.; Graham, B. H.; Grebe, T. A.; Lalani, S.; Irons, M.; Sparagana, S.; Williams, M.; Phillips, J. A.; Beaudet, A. L.; Stankiewicz, P.; Patel, A.; Cheung, S. W.; Sahoo, T.

    2010-01-01

    The 22q13.3 deletion syndrome results from loss of terminal segments of varying sizes at 22qter. Few genotype phenotype correlations have been found but all patients have mental retardation and severe delay, or absence of, expressive speech. We carried out clinical and molecular characterization of

  18. Molecular aspects of cutaneous T-cell lymphoma : genetic alterations underlying clinical behavior

    NARCIS (Netherlands)

    Kester, Maria Sophia van (Marloes)

    2012-01-01

    The research described in the thesis is focused at identifying molecular aberrations contributing to the pathogenesis of CTCL. In search for differences in chromosomal alterations underlying the different clinical behavior and prognosis of patients with mycosis fungoides (MF) and Sézary syndrome (Sz

  19. The Egyptian clinical trials’ registry profile: Analysis of three trial registries (International Clinical Trials Registry Platform, Pan-African Clinical Trials Registry and clinicaltrials.gov

    Directory of Open Access Journals (Sweden)

    Ahmed A. Zeeneldin

    2016-01-01

    Full Text Available Registering clinical trials (CTs in public domains enhances transparency, increases trust in research, improves participation and safeguards against publication bias. This work was done to study the profile of clinical research in Egypt in three CT registries with different scopes: the WHO International CT Registry Platform (ICTRP, the continental Pan-African CT Registry (PACTR and the US clinicaltrials.gov (CTGR. In March 2014, ICTRP, PACTR and CTGR were searched for clinical studies conducted in Egypt. It was found that the number of studies conducted in Egypt (percentage was 686 (0.30% in ICTRP, 56 (11.3% in PACTR and 548 (0.34% in CTGR. Most studies were performed in universities and sponsored by university/organization, industry or individual researchers. Inclusion of adults from both genders predominated. The median number of participants per study in the three registries ranged between 63 and 155. The conditions researched differed among the three registries and study purpose was mostly treatment followed by prevention. Endpoints were mostly efficacy followed by safety. Observational:Interventional studies (i.e. clinical trials represented 15.5%:84.5% in ICTRP, 0%:100% in PACTR and 16.4%:83.6% in CTGR. Most interventions were drugs or procedures. Observational studies were mostly prospective and cohort studies. Most CTs were phase 3 and tested drugs or procedures. Parallel group assignment and random allocation predominated. Blinding was implemented in many of trials and was mostly double-blind. We conclude that CTs from Egypt in trial registries are apparently low and do not accurately reflect clinical research conducted in Egypt or its potential. Development of an Egyptian CT registry is eagerly needed. Registering all Egyptian CTs in public domains is highly recommended.

  20. Molecular profiles of high-grade and low-grade pseudomyxoma peritonei.

    Science.gov (United States)

    Noguchi, Rei; Yano, Hideaki; Gohda, Yoshimasa; Suda, Ryuichiro; Igari, Toru; Ohta, Yasunori; Yamashita, Naohide; Yamaguchi, Kiyoshi; Terakado, Yumi; Ikenoue, Tsuneo; Furukawa, Yoichi

    2015-12-01

    Pseudomyxoma peritonei (PMP) is a rare disease exhibiting a distinct clinical feature caused by cancerous cells that produce mucinous fluid in the abdominal cavity. PMPs originate most frequently from the appendix and less frequently from the ovary. This disease can range from benign to malignant, and histologically, PMP is classified into two types: disseminated peritoneal adenomucinosis (DPAM) representing the milder phenotype, and peritoneal mucinous adenocarcinomas (PMCA) representing the aggressive phenotype. Although histological classification is clinically useful, the pathogenesis of PMP remains largely unknown. To elucidate the molecular mechanisms underlying PMP, we analyzed 18 PMP tumors comprising 10 DPAMs and 8 PMCAs. DNA was extracted from tumor and matched non-tumorous tissues, and was sequenced using Ion AmpliSeq Cancer Panel containing 50 cancer-related genes. Analysis of the data identified a total of 35 somatic mutations in 10 genes, and all mutations were judged as pathological mutations. Mutations were frequently identified in KRAS (14/18) and GNAS (8/18). Interestingly, TP53 mutations were found in three of the eight PMCAs, but not in the DPAMs. PIK3CA and AKT1 mutations were also identified in two PMCAs, but not in the DPAMs. These results suggested that KRAS and/or GNAS mutations are common genetic features of PMP, and that mutations in TP53 and/or genes related to the PI3K-AKT pathway may render malignant properties to PMP. These findings may be useful for the understanding of tumor characteristics, and facilitate the development of therapeutic strategies.

  1. Opportunities and challenges associated with clinical diagnostic genome sequencing: a report of the Association for Molecular Pathology.

    Science.gov (United States)

    Schrijver, Iris; Aziz, Nazneen; Farkas, Daniel H; Furtado, Manohar; Gonzalez, Andrea Ferreira; Greiner, Timothy C; Grody, Wayne W; Hambuch, Tina; Kalman, Lisa; Kant, Jeffrey A; Klein, Roger D; Leonard, Debra G B; Lubin, Ira M; Mao, Rong; Nagan, Narasimhan; Pratt, Victoria M; Sobel, Mark E; Voelkerding, Karl V; Gibson, Jane S

    2012-11-01

    This report of the Whole Genome Analysis group of the Association for Molecular Pathology illuminates the opportunities and challenges associated with clinical diagnostic genome sequencing. With the reality of clinical application of next-generation sequencing, technical aspects of molecular testing can be accomplished at greater speed and with higher volume, while much information is obtained. Although this testing is a next logical step for molecular pathology laboratories, the potential impact on the diagnostic process and clinical correlations is extraordinary and clinical interpretation will be challenging. We review the rapidly evolving technologies; provide application examples; discuss aspects of clinical utility, ethics, and consent; and address the analytic, postanalytic, and professional implications.

  2. Molecular Characterization and Expression Profiling of NAC Transcription Factors in Brachypodium distachyon L.

    Science.gov (United States)

    Zhu, Gengrui; Chen, Guanxing; Zhu, Jiantang; Zhu, Yan; Lu, Xiaobing; Li, Xiaohui; Hu, Yingkao; Yan, Yueming

    2015-01-01

    NAC (NAM, ATAF1/2, CUC2) transcription factors are involved in regulating plant developmental processes and response to environmental stresses. Brachypodium distachyon is an emerging model system for cereals, temperate grasses and biofuel crops. In this study, a comprehensive investigation of the molecular characterizations, phylogenetics and expression profiles under various abiotic stresses of the NAC gene family in Brachypodium distachyon was performed. In total, 118 BNAC genes in B. distachyon were identified, of which 22 (18.64%) were tandemly duplicated and segmentally duplicated, respectively. The Bayesian phylogenetic inference using Markov Chain Monte Carlo (MCMC) algorithms showed that they were divided into two clades and fourteen subfamilies, supported by similar motif compositions within one subfamily. Some critical amino acids detected using DIVERGE v3.0 might contribute to functional divergence among subfamilies. The different exon-intron organizations among subfamilies revealed structural differentiation. Promoter sequence predictions showed that the BNAC genes were involved in various developmental processes and diverse stress responses. Three NAC domain-encoding genes (BNAC012, BNAC078 and BNAC108), orthologous of NAC1, were targeted by five miRNA164 (Bdi-miR164a-c, e, f), suggesting that they might function in lateral organ enlargement, floral development and the responses to abiotic stress. Eleven (~9.32%) BNAC proteins containing α-helical transmembrane motifs were identified. 23 representative BNAC genes were analyzed by quantitative real-time PCR, showing different expression patterns under various abiotic stresses, of which 18, 17 and 11 genes were up-regulated significantly under drought, H2O2 and salt stresses, respectively. Only four and two genes were up-regulated under cold and cadmium stresses, respectively. Dynamic transcriptional expression analysis revealed that six genes showed constitutive expression and period

  3. Molecular Characterization and Expression Profiling of NAC Transcription Factors in Brachypodium distachyon L.

    Directory of Open Access Journals (Sweden)

    Gengrui Zhu

    Full Text Available NAC (NAM, ATAF1/2, CUC2 transcription factors are involved in regulating plant developmental processes and response to environmental stresses. Brachypodium distachyon is an emerging model system for cereals, temperate grasses and biofuel crops. In this study, a comprehensive investigation of the molecular characterizations, phylogenetics and expression profiles under various abiotic stresses of the NAC gene family in Brachypodium distachyon was performed. In total, 118 BNAC genes in B. distachyon were identified, of which 22 (18.64% were tandemly duplicated and segmentally duplicated, respectively. The Bayesian phylogenetic inference using Markov Chain Monte Carlo (MCMC algorithms showed that they were divided into two clades and fourteen subfamilies, supported by similar motif compositions within one subfamily. Some critical amino acids detected using DIVERGE v3.0 might contribute to functional divergence among subfamilies. The different exon-intron organizations among subfamilies revealed structural differentiation. Promoter sequence predictions showed that the BNAC genes were involved in various developmental processes and diverse stress responses. Three NAC domain-encoding genes (BNAC012, BNAC078 and BNAC108, orthologous of NAC1, were targeted by five miRNA164 (Bdi-miR164a-c, e, f, suggesting that they might function in lateral organ enlargement, floral development and the responses to abiotic stress. Eleven (~9.32% BNAC proteins containing α-helical transmembrane motifs were identified. 23 representative BNAC genes were analyzed by quantitative real-time PCR, showing different expression patterns under various abiotic stresses, of which 18, 17 and 11 genes were up-regulated significantly under drought, H2O2 and salt stresses, respectively. Only four and two genes were up-regulated under cold and cadmium stresses, respectively. Dynamic transcriptional expression analysis revealed that six genes showed constitutive expression and period

  4. Molecular characterization and expression profiling of the protein disulfide isomerase gene family in Brachypodium distachyon L.

    Directory of Open Access Journals (Sweden)

    Chong Zhu

    Full Text Available Protein disulfide isomerases (PDI are involved in catalyzing protein disulfide bonding and isomerization in the endoplasmic reticulum and functions as a chaperone to inhibit the aggregation of misfolded proteins. Brachypodium distachyon is a widely used model plant for temperate grass species such as wheat and barley. In this work, we report the first molecular characterization, phylogenies, and expression profiles of PDI and PDI-like (PDIL genes in B. distachyon in different tissues under various abiotic stresses. Eleven PDI and PDIL genes in the B. distachyon genome by in silico identification were evenly distributed across all five chromosomes. The plant PDI family has three conserved motifs that are involved in catalyzing protein disulfide bonding and isomerization, but a different exon/intron structural organization showed a high degree of structural differentiation. Two pairs of genes (BdPDIL4-1 and BdPDIL4-2; BdPDIL7-1 and BdPDIL7-2 contained segmental duplications, indicating each pair originated from one progenitor. Promoter analysis showed that Brachypodium PDI family members contained important cis-acting regulatory elements involved in seed storage protein synthesis and diverse stress response. All Brachypodium PDI genes investigated were ubiquitously expressed in different organs, but differentiation in expression levels among different genes and organs was clear. BdPDIL1-1 and BdPDIL5-1 were expressed abundantly in developing grains, suggesting that they have important roles in synthesis and accumulation of seed storage proteins. Diverse treatments (drought, salt, ABA, and H2O2 induced up- and down-regulated expression of Brachypodium PDI genes in seedling leaves. Interestingly, BdPDIL1-1 displayed significantly up-regulated expression following all abiotic stress treatments, indicating that it could be involved in multiple stress responses. Our results provide new insights into the structural and functional characteristics of the

  5. Clinical profile of parkinsonism and Parkinson's disease in Lagos, Southwestern Nigeria

    Directory of Open Access Journals (Sweden)

    Ojo Oluwadamilola O

    2010-01-01

    Full Text Available Abstract Background Current data on the pattern of parkinsonism and Parkinson's disease in Nigerians are sparse. This database was designed to document the clinical profile of PD in Nigerians, and compare this to prior observations. Methods A database of patients presenting to the Neurology out-patients clinic of the Lagos University Teaching Hospital was established in October 1996. Demographic and clinical data at presentation (disease stage using Hoehn and Yahr scale; 'off' state severity on the Unified Parkinson's disease Rating Scale were documented for patients diagnosed with parkinsonism between October 1996 and December 2006. Cases were classified as Parkinson's disease or secondary parkinsonism (in the presence of criteria suggestive of a secondary aetiology. Results The hospital frequency of parkinsonism (over a 2-year period, and relative to other neurologic disorders was 1.47% (i.e. 20/1360. Of the 124 patients with parkinsonism, 98 (79.0% had PD, while 26 (21.0% had secondary parkinsonism. Mean age (SD at onset of PD (61.5 (10.0 years was slightly higher than for secondary parkinsonism (57.5 (14.0 years (P = 0.10. There was a male preponderance in PD (3.3 to 1 and secondary parkinsonism (2.7 to 1, while a positive family history of parkinsonism was present in only 1.02% (1/98 of PD. There was a modestly significant difference in age at onset (SD of PD in men (60.3 (10.4 compared to women (65.2 (7.9 (T = 2.08; P = 0.04. The frequency of young onset PD (≤ 50 years was 16.3% (16/98. The mean time interval from onset of motor symptoms to diagnosis of PD was 24.6 ± 26.1 months with majority presenting at a median 12 months from onset. On the H&Y scale, severity of PD at presentation was a median 2.0 (range 1 to 4. PD disease subtype was tremor-dominant in 31 (31.6%, mixed 54 (55.1% and akinetic-rigid 14 (14.3%. Hypertension was present as a co-morbidity in 20 (20.4%, and diabetes in 6 (6.12%. Conclusions The clinical profile of PD in

  6. Clinical profile and outcomes of atrial fibrillation in elderly patients with acute myocardial infarction

    Institute of Scientific and Technical Information of China (English)

    LI Kang; HUO Yong; DING Yan-sheng

    2008-01-01

    Background Atrial fibrillation (AF) occurs commonly in patients with acute myocardial infarction (MI) and is associated with an increased long-term mortality.This study aimed to investigate the clinical characteristics and outcomes of AF in in-hospital elderly Chinese patients with acute MI.Methods A total of 967 patients with acute MI,aged≥65 years,were categorized on the basis of the absence or presence of AF.Patients with documented AF were classified into two subgroups: the ongoing AF group and the new-onset AF group.We retrospectively evaluated the clinical profile,in-hospital outcomes,and effects of revascularization on the incidence of AF in elderly patients with acute MI.Results AF was documented in 100 (11.53%) patients and the incidence of new-onset AF was 6.51% during hospitalization.History of old MI and cerebrovascular events were more common in patients with AF than in those without AF (P<0.001,P<0.01,respectively).The incidence of AF was higher in patients with non-ST elevated MI (P=0.014),inferior wall MI (P=0.004) and cardiac function of Killip class III or IV (P=0.008).Patients with AF had more complication of pneumonia (P=0.003) and longer hospital stay.Left circumflex coronary artery involvement was more common in patients with AF (compared with patients without AF,P <0.001).Percutaneous coronary intervention or coronary artery bypass grafting significantly decreased the incidence of new-onset AF from 7.97% to 3.82% (P=0.017).AF depended to heart failure,increased the in-hospital mortality.Conclusions AF is common in elderly patients with acute MI and is associated with poorer clinical outcomes.Revascularization reduces the incidence of AF and thus improves the clinical outcomes in these patients.

  7. Clinical and epidemiological profile of leprosy patients attended at Ceará, 2007-2011*

    Science.gov (United States)

    Queirós, Maria Iranilda; Ramos Júnior, Alberto Novaes; Alencar, Carlos Henrique Morais; Monteiro, Lorena Dias; Sena, Amanda Lima; Barbosa, Jaqueline Caracas

    2016-01-01

    Background Leprosy is an infectious chronic condition associated with potentially serious physical, social and psychological impacts. Objectives To characterize the clinical and epidemiological profile of leprosy patients treated from 2007 to 2011 in the University Hospital of Ceará, Northeastern Brazil. Methods This is a retrospective and descriptive study. The study population consisted of residents in the state of Ceará treated in a dermatology clinic between 2007-2011. Clinical and epidemiological data analyzed were obtained from medical records and from the database of national Information System for Notifiable Diseases. Results 475 cases were analyzed, mostly women (51.8%), aged 45-59 years (35.0%) - mean of 45.2 years at diagnosis - with 6.3% of children under 15 , with low education (73.7%), white color (68.8%), residency in the city of Fortaleza (82.3%), and no defined work occupation (59.6%). At diagnosis, most patients were multibacillary (MB) (65.5%), had borderline clinical form (48.0%), and 22.7% had physical disability (8.0% with grade 2), predominantly in MB cases (p <0.001). We observe worsening of disability in 5.1% of cases post-MDT. The proportion of cases with reactional episodes was 42.7%, mainly during MDT (51.2%). Conclusion This is the first study conducted in this hospital context, revealing late diagnosis, high burden of disease, hidden endemicity, and high social vulnerability in the state of Ceará. This study reinforces the need to strengthen health care network for timely diagnosis and treatment, aiming at longitudinality of assistance. PMID:27438198

  8. Aromatic L-amino acid decarboxylase deficiency diagnosed by clinical metabolomic profiling of plasma.

    Science.gov (United States)

    Atwal, Paldeep S; Donti, Taraka R; Cardon, Aaron L; Bacino, C A; Sun, Qin; Emrick, L; Reid Sutton, V; Elsea, Sarah H

    2015-01-01

    Aromatic L-amino acid decarboxylase (AADC) deficiency is an inborn error of metabolism affecting the biosynthesis of serotonin, dopamine, and catecholamines. We report a case of AADC deficiency that was detected using the Global MAPS platform. This is a novel platform that allows for parallel clinical testing of hundreds of metabolites in a single plasma specimen. It uses a state-of-the-art mass spectrometry platform, and the resulting spectra are compared against a library of ~2500 metabolites. Our patient is now a 4 year old boy initially seen at 11 months of age for developmental delay and hypotonia. Multiple tests had not yielded a diagnosis until exome sequencing revealed compound heterozygous variants of uncertain significance (VUS), c.286G>A (p.G96R) and c.260C>T (p.P87L) in the DDC gene, causal for AADC deficiency. CSF neurotransmitter analysis confirmed the diagnosis with elevated 3-methoxytyrosine (3-O-methyldopa). Metabolomic profiling was performed on plasma and revealed marked elevation in 3-methoxytyrosine (Z-score +6.1) consistent with the diagnosis of AADC deficiency. These results demonstrate that the Global MAPS platform is able to diagnose AADC deficiency from plasma. In summary, we report a novel and less invasive approach to diagnose AADC deficiency using plasma metabolomic profiling.

  9. DNA methylation profiling identifies two splenic marginal zone lymphoma subgroups with different clinical and genetic features.

    Science.gov (United States)

    Arribas, Alberto J; Rinaldi, Andrea; Mensah, Afua A; Kwee, Ivo; Cascione, Luciano; Robles, Eloy F; Martinez-Climent, Jose A; Oscier, David; Arcaini, Luca; Baldini, Luca; Marasca, Roberto; Thieblemont, Catherine; Briere, Josette; Forconi, Francesco; Zamò, Alberto; Bonifacio, Massimiliano; Mollejo, Manuela; Facchetti, Fabio; Dirnhofer, Stephan; Ponzoni, Maurilio; Bhagat, Govind; Piris, Miguel A; Gaidano, Gianluca; Zucca, Emanuele; Rossi, Davide; Bertoni, Francesco

    2015-03-19

    Splenic marginal zone lymphoma is a rare lymphoma. Loss of 7q31 and somatic mutations affecting the NOTCH2 and KLF2 genes are the commonest genomic aberrations. Epigenetic changes can be pharmacologically reverted; therefore, identification of groups of patients with specific epigenomic alterations might have therapeutic relevance. Here we integrated genome-wide DNA-promoter methylation profiling with gene expression profiling, and clinical and biological variables. An unsupervised clustering analysis of a test series of 98 samples identified 2 clusters with different degrees of promoter methylation. The cluster comprising samples with higher-promoter methylation (High-M) had a poorer overall survival compared with the lower (Low-M) cluster. The prognostic relevance of the High-M phenotype was confirmed in an independent validation set of 36 patients. In the whole series, the High-M phenotype was associated with IGHV1-02 usage, mutations of NOTCH2 gene, 7q31-32 loss, and histologic transformation. In the High-M set, a number of tumor-suppressor genes were methylated and repressed. PRC2 subunit genes and several prosurvival lymphoma genes were unmethylated and overexpressed. A model based on the methylation of 3 genes (CACNB2, HTRA1, KLF4) identified a poorer-outcome patient subset. Exposure of splenic marginal zone lymphoma cell lines to a demethylating agent caused partial reversion of the High-M phenotype and inhibition of proliferation. PMID:25612624

  10. Aromatic L-amino acid decarboxylase deficiency diagnosed by clinical metabolomic profiling of plasma.

    Science.gov (United States)

    Atwal, Paldeep S; Donti, Taraka R; Cardon, Aaron L; Bacino, C A; Sun, Qin; Emrick, L; Reid Sutton, V; Elsea, Sarah H

    2015-01-01

    Aromatic L-amino acid decarboxylase (AADC) deficiency is an inborn error of metabolism affecting the biosynthesis of serotonin, dopamine, and catecholamines. We report a case of AADC deficiency that was detected using the Global MAPS platform. This is a novel platform that allows for parallel clinical testing of hundreds of metabolites in a single plasma specimen. It uses a state-of-the-art mass spectrometry platform, and the resulting spectra are compared against a library of ~2500 metabolites. Our patient is now a 4 year old boy initially seen at 11 months of age for developmental delay and hypotonia. Multiple tests had not yielded a diagnosis until exome sequencing revealed compound heterozygous variants of uncertain significance (VUS), c.286G>A (p.G96R) and c.260C>T (p.P87L) in the DDC gene, causal for AADC deficiency. CSF neurotransmitter analysis confirmed the diagnosis with elevated 3-methoxytyrosine (3-O-methyldopa). Metabolomic profiling was performed on plasma and revealed marked elevation in 3-methoxytyrosine (Z-score +6.1) consistent with the diagnosis of AADC deficiency. These results demonstrate that the Global MAPS platform is able to diagnose AADC deficiency from plasma. In summary, we report a novel and less invasive approach to diagnose AADC deficiency using plasma metabolomic profiling. PMID:25956449

  11. Cytokine profile and clinical metabolic alterations in HIV-1 infected individuals with and without lipodistrophy

    Directory of Open Access Journals (Sweden)

    L. C. R. Pontes-Cardoso

    2007-01-01

    Full Text Available The extensive use of Highly Active Antiretroviral Therapy (HAART has transformed HIV infection into a chronic condition. Thus, metabolic alterations including lipodystrophy and dyslipidemia have been associated with the use of such medications. The objective of the present study was to analyze clinical metabolic alterations and the profile of TNF-alpha, IFN-Y, IL-2, IL-10, and TNF-alpha type II soluble receptor in serum of HIV-1 individuals with and without lipodystrophy. Eighty-four adults were evaluated, 42 males and 42 females, mean age 37 years, and HAART time of at least 15 months. Two groups were formed, G1: 42 individuals with lipodystrophy, and G2: 42 without lipodistropy. From the HAART used, stavudine was more associated with the lipodystrophy group and zidovudine with the non-lipodystrophy group. CD4 and CD8 values, viral load, glucose, albumin, and lipids were not different between groups, except for triglycerides, which were high in the lipodystrophy group, and HDL, whose concentration was reduced in G1. TNF-alpha, TNF-RII, and IL-10 profiles were high and had positive correlation; IL-2 and IFN-gamma had reduced levels in the lipodystrophy group. High TNF-alpha and its receptor levels seem to be associated with lipodystrophy development in individuals under HAART therapy.

  12. Serum lipid profile and clinical characteristics of patients with xanthelasma palpebrarum*

    Science.gov (United States)

    Kavoussi, Hossein; Ebrahimi, Ali; Rezaei, Mansour; Ramezani, Mazaher; Najafi, Behnaz; Kavoussi, Reza

    2016-01-01

    Background Although many factors are involved in the etiology of xanthelasma palpebrum, lipid disorder is strongly associated with its induction. Xanthelasma palpebrum, the most common type of xanthoma, usually presents in middle-aged females and results in aesthetic problems. Objective To evaluate thelipid profile and important clinical aspects of xanthelasma palpebrum patients. Methods In this descriptive study, we enrolled 42xanthelasma palpebrumpatients, and 42 cases of non-inflammatory skin disorders as thecontrol group, matched for age and gender.The clinical characteristics of the patients and fasting serum lipid profile were recorded for both groups. The data obtained were analyzed using SPSS-16. Results Xanthelasma palpebrum was found more commonly in middle-aged females with disease onset of less than 1 year, and without significant familial history of xanthoma. Furthermore,xanthelasma lesionswere most often seen in the upper lid with mild extension and was rarely associated with systemic disease. There was no statistically significant difference between two groups regarding hypertriglyceridemia (p= 0.231) and hypercholesterolemia (p= 0.302). The mean serum levels of cholesterol (221.51±60.4 mg/dl), triglyceride (185.98±71.1 mg/dl) and VLDL (37.7±17.6 mg/dl) were significantly higher and themedian HDL (36.2 (31, 41) mg/dl) level was lower in thepatient group. Conclusion In our study, hypercholesterolemia and hypertriglyceridemia did not reveal a significant difference between thepatient and control groups; however, mean serum values for cholesterol, triglyceride, VLDL and HDL showed a significant difference between the two groups. Therefore, in addition to lipid abnormality, other factors could be involved in the pathogenesis of xanthelasma palpebrum. PMID:27579742

  13. CLINICAL PROFILE OF HEMOPHILIA PATIENTS: A CROSS SECTIONAL STUDY AT A TERTIARY CARE CENTER IN INDIA

    Directory of Open Access Journals (Sweden)

    Ram Sunder

    2015-12-01

    Full Text Available The study was designed to determine clinical profile of haemophilia patients in North India. In this cross-sectional study, we obtained family history and clinical profile of 54 diagnosed severe haemophilia patients attending Haemophilia Treatment Centre, Children Hospital LLR Hospital, Kanpur, India, for factor replacement therapy. We also obtained blood samples to investigate for hepatitis B, HIV. In study we observed that majority of the patients having their first presentation in their infancy (70.3% and median age of first presentation was 11 months of age. Though haemophilia is a genetic disorder, family history was negative in majority of patients; (70.3% subcutaneous tissue was most frequent site for initial bleeds, but as age advances joints become frequently involved and hemarthrosis was commonest complication affecting 79.6% patients. Most common involved joint was knee joint (53.7%. This hemarthrosis is the major cause of morbidity affecting quality of life of patients. Due to cost of treatment, many times we have to transfuse blood and blood products which may lead to Transfusion Transmitted Infection (TTI. In our study prevalence of TTI was 1.85% and 3.70% for HIV and Hep. B respectively. We also observed that there was time lag of >1 month in 16.5% cases between onset of symptom and definitive diagnosis, which shows lack of awareness among doctors in community. In view of this high morbidity and TTIs, we emphasize the free availability of factor concentrates and prophylactic treatment should be followed instead of palliative treatment.

  14. Amelogenin: A novel protein with diverse applications in genetic and molecular profiling

    Directory of Open Access Journals (Sweden)

    Ajay Kumar Bansal

    2012-01-01

    Full Text Available Tooth enamel is a unique entity among all mineralized tissues because of the presence of high mineral content. It is non collagenous and does not undergo resorption and remodelling. Its formation occurs through a transient collaborating network of enamel matrix proteins which controls hydroxyapatite crystal growth and orientation. Amelogenins constitute about 90% of the total enamel matrix proteins and play a major role in enamel bio mineralization. Amelogenin isoforms coalesce into nanospheres thus dictating the width and thickness of apatite crystals. The X and Y copies of amelogenins do not undergo homologous recombination, thus preferring it for sex determination in modern forensics. Recently, it was discovered that application of amelogenin to diseased periodontal tissue surfaces enhanced the regeneration of all the periodontal tissues. Additionally, low molecular mass amelogenin polypeptides have also been thought to possess osteogenic potential. Recent data regarding usage of immunohistochemical markers for mesenchymal stem cells suggested that amelogenin has the capacity to induce the recruitment of mesenchymal stem cells directly or indirectly during regeneration of the supporting periodontal tissues. Thus, our current concepts of dental enamel formation should be reviewed thoroughly so that this information could be applied to clinical circumstances where this understanding may be particularly relevant.

  15. Molecular and Cellular Profiling of Scalp Psoriasis Reveals Differences and Similarities Compared to Skin Psoriasis.

    Science.gov (United States)

    Ruano, Juan; Suárez-Fariñas, Mayte; Shemer, Avner; Oliva, Margeaux; Guttman-Yassky, Emma; Krueger, James G

    2016-01-01

    Scalp psoriasis shows a variable clinical spectrum and in many cases poses a great therapeutic challenge. However, it remains unknown whether the immune response of scalp psoriasis differs from understood pathomechanisms of psoriasis in other skin areas. We sought to determine the cellular and molecular phenotype of scalp psoriasis by performing a comparative analysis of scalp and skin using lesional and nonlesional samples from 20 Caucasian subjects with untreated moderate to severe psoriasis and significant scalp involvement and 10 control subjects without psoriasis. Our results suggest that even in the scalp, psoriasis is a disease of the inter-follicular skin. The immune mechanisms that mediate scalp psoriasis were found to be similar to those involved in skin psoriasis. However, the magnitude of dysregulation, number of differentially expressed genes, and enrichment of the psoriatic genomic fingerprint were more prominent in skin lesions. Furthermore, the scalp transcriptome showed increased modulation of several gene-sets, particularly those induced by interferon-gamma, compared with that of skin psoriasis, which was mainly associated with activation of TNFα/L-17/IL-22-induced keratinocyte response genes. We also detected differences in expression of gene-sets involving negative regulation, epigenetic regulation, epidermal differentiation, and dendritic cell or Th1/Th17/Th22-related T-cell processes.

  16. Molecular interaction of a kinase inhibitor midostaurin with anticancer drug targets, S100A8 and EGFR: transcriptional profiling and molecular docking study for kidney cancer therapeutics.

    Directory of Open Access Journals (Sweden)

    Zeenat Mirza

    Full Text Available The S100A8 and epidermal growth factor receptor (EGFR proteins are proto-oncogenes that are strongly expressed in a number of cancer types. EGFR promotes cellular proliferation, differentiation, migration and survival by activating molecular pathways. Involvement of proinflammatory S100A8 in tumor cell differentiation and progression is largely unclear and not studied in kidney cancer (KC. S100A8 and EGFR are potential therapeutic biomarkers and anticancer drug targets for KC. In this study, we explored molecular mechanisms of interaction profiles of both molecules with potential anticancer drugs. We undertook transcriptional profiling in Saudi KCs using Affymetrix HuGene 1.0 ST arrays. We identified 1478 significantly expressed genes, including S100A8 and EGFR overexpression, using cut-off p value <0.05 and fold change ≥2. Additionally, we compared and confirmed our findings with expression data available at NCBI's GEO database. A significant number of genes associated with cancer showed involvement in cell cycle progression, DNA repair, tumor morphology, tissue development, and cell survival. Atherosclerosis signaling, leukocyte extravasation signaling, notch signaling, and IL-12 signaling were the most significantly disrupted signaling pathways. The present study provides an initial transcriptional profiling of Saudi KC patients. Our analysis suggests distinct transcriptomic signatures and pathways underlying molecular mechanisms of KC progression. Molecular docking analysis revealed that the kinase inhibitor "midostaurin" has amongst the selected drug targets, the best ligand properties to S100A8 and EGFR, with the implication that its binding inhibits downstream signaling in KC. This is the first structure-based docking study for the selected protein targets and anticancer drug, and the results indicate S100A8 and EGFR as attractive anticancer targets and midostaurin with effective drug properties for therapeutic intervention in KC.

  17. The Morphologic Profile of HPV-Related Head and Neck Squamous Carcinoma: Implications for Diagnosis, Prognosis, and Clinical Management

    OpenAIRE

    Westra, William H.

    2012-01-01

    Much recent attention has highlighted a subset of head and neck squamous cell carcinomas (HNSCCs) related to the human papillomavirus (HPV) that is characterized by an epidemiologic, demographic, and clinical profile that deviates from the profile of conventional non-HPV-related HNSCC. Lost in the dash to develop and implement diagnostic assays to detect the presence of HPV in HNSCCs is the unpretentious observation that these HPV-HNSCCs are also distinctive with respect to their microscopic ...

  18. Characterization and genetic variability of feed-borne and clinical animal/human Aspergillus fumigatus strains using molecular markers.

    Science.gov (United States)

    Pena, Gabriela A; Coelho, Irene; Reynoso, María M; Soleiro, Carla; Cavaglieri, Lilia R

    2015-09-01

    Aspergillus fumigatus, the major etiological agent of human and animal aspergillosis, is a toxigenic fungus largely regarded as a single species by macroscopic and microscopic features. However, molecular studies have demonstrated that several morphologically identified A. fumigatus strains might be genetically distinct. This work was aimed to apply PCR-restriction length fragment polymorphisms (PCR-RFLP) and random amplification of polymorphic DNA (RAPD) molecular markers to characterize a set of feed-borne and clinical A. fumigatus sensu lato strains isolated from Argentina and Brazil and to determine and compare their genetic variability. All A. fumigatus strains had the same band profile and those typical of A. fumigatus sensu stricto positive controls by PCR-RFLP. Moreover, all Argentinian and Brazilian strains typified by RAPD showed similar band patterns to each other and to A. fumigatus sensu stricto reference strains regardless of their isolation source (animal feeds or human/animal clinical cases) and geographic origin. Genetic similarity coefficients ranged from 0.61 to 1.00, but almost all isolates showed 78% of genetic similarly suggesting that genetic variability was found at intraspecific level. Finally, benA sequencing confirmed its identification as A. fumigatus sensu stricto species. These results suggest that A. fumigatus sensu stricto is a predominant species into Aspergillus section Fumigati found in animal environments as well as in human/animal clinical cases, while other species may be rarely isolated. The strains involved in human and animal aspergillosis could come from the environment where this fungus is frequently found. Rural workers and animals would be constantly exposed.

  19. Analysis of Requirements for the Medication Profile to Be Used in Clinical Research: Protocol Feasibility Studies and Patient Recruitment

    Directory of Open Access Journals (Sweden)

    Julie M. James

    2015-01-01

    Full Text Available A “Medication Profile,” the information about the medicines a person is using and has used, is a core part of many electronic health record systems and summaries. However, there is little objective research into the data elements that the profile should contain to support the uses it must serve. With the increasing emphasis on secondary uses of electronic health information, as well as supporting the requirements to support direct to patient care, the Medication Profile should also support the requirements from clinical research. However, there is little, if any, description of these available. This paper describes an analysis of a set of study eligibility criteria that was undertaken to investigate which medication-related data elements would be required to support two clinical research use cases: the parameters to query a patient’s Medication Profile to assess their suitability for entry into a trial (patient recruitment and the parameters to query a set of Medication Profiles in a data warehouse to assess whether the eligibility criteria as described would yield a reasonable cohort of patients as potential subjects (protocol feasibility. These medication-related data elements then become information requirements that a Medication Profile should ideally meet, in order to be able to support these two uses in the clinical research domain.

  20. Urgency in Pediatric Dentistry: Care Profile of the Integrated Pediatric Clinic of FOUFAL

    Directory of Open Access Journals (Sweden)

    Noelle Albuquerque AMORIM

    2007-09-01

    Full Text Available Objective: To analyze the profile of the urgency care provided atthe Integrated Pediatric Clinic of the School of Dentistry of theFederal University of Alagoas (FOUFAL.Method: 221 patient files were analyzed between April toNovember 2006 and the following data were analyzed by descriptivestatistics: patient identification, type of urgency, involved tooth(teeth, diagnosis and proposed treatment. Only complete files wereincluded.Results: Urgency care was most frequently sought by femalechildren (55.7%; the age ranged between 2 and 14 years (meanage =7.6 years; toothache was the most common cause of urgencycare (53.84%; most cases of dental urgencies involved primarymandibular second molars (34.7%; the maxillary central incisorswere the most affected by traumatic injuries in both the primary(78.5% and permanent (76.2% dentitions; extraction (44% wasthe most common dental procedure followed by root canal therapy(34.5% and restorative treatment (24.5%; dental caries (48.3%was the diagnosis most frequently associated with toothachefollowed by irreversible pulpitis (22.8% and reversible pulpitis(16.1%.Conclusions: Most patients that sought treatment at the UrgencyService of the Pediatric Dentistry Clinic at FOUFAL were femalechildren with a low socioeconomic level. Toothache was the mostfrequent reason for the urgency appointments, extraction was themost common procedure, affecting mainly the primary dentition andthe mandibular second molars.

  1. The institutionalized elderly: sociodemographic and clinical-functional profiles related to dizziness

    Directory of Open Access Journals (Sweden)

    Tábada Samantha Marques Rosa

    2016-04-01

    Full Text Available ABSTRACT INTRODUCTION: Dizziness is among the most common complaints in the elderly population. OBJECTIVE: To determine the sociodemographic and clinical-functional profiles of institutionalized elderly people related to dizziness. METHODS: Cross-sectional prospective study with institutionalized elderly people aged 60 or more years. A questionnaire on sociodemographic and clinical-functional characteristics was applied, and an anamnesis of occurrence of dizziness was held, as well as the Dizziness Handicap Inventory questionnaire. RESULTS: 48.9% of the elderly subjects had dizziness. The mean numbers of diseases and medications associated with dizziness were, respectively, 4.5 diseases and 7.8 medications. We found a significant association between the occurrence of dizziness and diseases of the musculoskeletal system, sub-connective tissue and genitourinary system, as well as the use of medications for the musculoskeletal system. The scores for handicap degree in functional DHI were significantly higher among elderly subjects who needed walking aids, who had suffered falls, and those manifesting anxiety. CONCLUSION: Our sample included subjects of advanced age, primarily women, who were institutionalized less than five years, with multiple diseases and polypharmacy users. They presented long-standing short-duration mixed dizziness, that occurred more than once a month and affected mainly the functional aspect.

  2. Integrative Transcriptomic and Metabonomic Molecular Profiling of Colonic Mucosal Biopsies Indicates a Unique Molecular Phenotype for Ulcerative Colitis

    DEFF Research Database (Denmark)

    Rantalainen, Mattias; Bjerrum, Jacob Tveiten; Olsen, Jørgen;

    2015-01-01

    Ulcerative colitis is the most prevailing entity of several disorders under the umbrella term inflammatory bowel disease, with potentially serious symptoms and devastating consequences for affected patients. The exact molecular etiology of ulcerative colitis is not yet revealed. In this study, we...

  3. Asperger syndrome in India: Findings from a case-series with respect to clinical profile and comorbidity

    Directory of Open Access Journals (Sweden)

    Priya Sreedaran

    2015-01-01

    Full Text Available Asperger syndrome (AS is an autism spectrum disorder with a high rate of psychiatric comorbidity. We describe the clinical profile and psychiatric comorbidity in a series of affected individuals referred to an Indian general hospital psychiatry setting. Gilliam Asperger′s disorder scale was used to evaluate the clinical characteristics while Mini-International Neuropsychiatric Interview (MINI-KID and MINI-PLUS were used to assess psychiatric comorbidity. The profile of subjects with AS in our case-series appears similar to that published elsewhere with high rates of psychiatric comorbidity. Mental health professionals should evaluate for psychiatric comorbidity in individuals with autism spectrum disorders.

  4. Asperger syndrome in India: findings from a case-series with respect to clinical profile and comorbidity.

    Science.gov (United States)

    Sreedaran, Priya; Ashok, M V

    2015-01-01

    Asperger syndrome (AS) is an autism spectrum disorder with a high rate of psychiatric comorbidity. We describe the clinical profile and psychiatric comorbidity in a series of affected individuals referred to an Indian general hospital psychiatry setting. Gilliam Asperger's disorder scale was used to evaluate the clinical characteristics while Mini-International Neuropsychiatric Interview (MINI)-KID and MINI-PLUS were used to assess psychiatric comorbidity. The profile of subjects with AS in our case-series appears similar to that published elsewhere with high rates of psychiatric comorbidity. Mental health professionals should evaluate for psychiatric comorbidity in individuals with autism spectrum disorders.

  5. Asperger syndrome in India: findings from a case-series with respect to clinical profile and comorbidity.

    Science.gov (United States)

    Sreedaran, Priya; Ashok, M V

    2015-01-01

    Asperger syndrome (AS) is an autism spectrum disorder with a high rate of psychiatric comorbidity. We describe the clinical profile and psychiatric comorbidity in a series of affected individuals referred to an Indian general hospital psychiatry setting. Gilliam Asperger's disorder scale was used to evaluate the clinical characteristics while Mini-International Neuropsychiatric Interview (MINI)-KID and MINI-PLUS were used to assess psychiatric comorbidity. The profile of subjects with AS in our case-series appears similar to that published elsewhere with high rates of psychiatric comorbidity. Mental health professionals should evaluate for psychiatric comorbidity in individuals with autism spectrum disorders. PMID:25969609

  6. Detection of clarithromycin-resistant Helicobacter pylori in clinical specimens by molecular methods: A review.

    Science.gov (United States)

    Xuan, Shi-Hai; Wu, Li-Pei; Zhou, Yu-Gui; Xiao, Ming-Bing

    2016-03-01

    Various molecular methods have been developed to rapidly detect clarithromycin (CLR) resistance in Helicobacter pylori isolates in clinical specimens. All of these assays for detecting CLR resistance in H. pylori are based on detection of mutations in the 23S rRNA gene. In this article, we summarise current knowledge regarding the detection of H. pylori CLR resistance in clinical specimens by molecular tests. The available data showed that restriction fragment length polymorphism (RFLP), 3'-mismatch PCR, DNA sequencing, the PCR line probe assay (PCR-LiPA) and fluorescence in situ hybridisation assay (FISH) are able to detect CLR-resistant H. pylori in clinical specimens with excellent specificity and sensitivity. However, several factors limit their clinical application, including fastidious, time-consuming preparation and low-throughput as well as carrying a risk of contamination. Furthermore, as an invasive method, FISH is not suitable for children or the elderly. Among the molecular methods, one that is most promising for the future is real-time PCR probe hybridisation technology using fluorescence resonance energy transfer (FRET) probes, which can rapidly detect CLR resistance with high sensitivity and specificity in biopsies and stool specimens, even though mixed infections are present in clinical specimens. Moreover, due to the advantages that this method is simple, rapid and economical, real-time PCR is technically feasible for clinical application in small- and medium-sized hospitals in developing countries. Second, with high sensitivity, specificity and throughput, DNA chips will also be a valuable tool for detecting resistant H. pylori isolates from cultures and clinical specimens. PMID:27436390

  7. Epidemiological, Clinical and Prognostic Profile of Acute Bacterial Meningitis among Children in Alexandria, Egypt

    Directory of Open Access Journals (Sweden)

    Farag HF

    2005-01-01

    Full Text Available Purpose: To address the epidemiological characteristics and clinical indices that may predict the prognostic profile of meningitis among children. Methods: Children admitted to Alexandria fever hospital with clinical diagnosis of meningitis/meningoencephalitis during the period 2002-2003 were recruited for the study. They were subjected to clinical examination as well as CSF bacteriological and serological investigations Results: Three hundred and ten patients (195 males and 115 females were included. About 65.2% of them were infected with acute bacterial meningitis (ABM and 34.8% were infected with aseptic meningitis. In this study, ABM was caused by Haemophilus influenzae (21%, Streptococcus pneumoniae (13.9%, Neisseria meningitidis (14.2% and other undetermined bacteria (16.1%. ABM showed significant association with age group 1-9 years (66.3%, low socio-economic class (96%, working mother (83.2%, more than two smokers in the family (62.9% and cold seasons(fall 35.1% and winter 48.5%. Aseptic meningitis showed significant association with age group 3-15 months (100% and previous immunization(81.5%. The overall case fatality rate was 10.3%; 13.9% for ABM and 3.4% for aseptic meningitis. 7.1% of all survivors developed epileptic attacks. Predictors for death or epilepsy events were high WHO meningitis score (> 9, decreased CSF glucose level (Conclusion: This study highlights the importance of several predictors of the outcome of meningitis in children. It is concluded that quick and simple scoring scales, such as the WHO scale, are not only applicable but valuable prognostic tools for meningitis in children.

  8. Whole Blood Gene Expression Profiling in Preclinical and Clinical Cattle Infected with Atypical Bovine Spongiform Encephalopathy.

    Science.gov (United States)

    Xerxa, Elena; Barbisin, Maura; Chieppa, Maria Novella; Krmac, Helena; Vallino Costassa, Elena; Vatta, Paolo; Simmons, Marion; Caramelli, Maria; Casalone, Cristina; Corona, Cristiano; Legname, Giuseppe

    2016-01-01

    Prion diseases, such as bovine spongiform encephalopathies (BSE), are transmissible neurodegenerative disorders affecting humans and a wide variety of mammals. Variant Creutzfeldt-Jakob disease (vCJD), a prion disease in humans, has been linked to exposure to BSE prions. This classical BSE (cBSE) is now rapidly disappearing as a result of appropriate measures to control animal feeding. Besides cBSE, two atypical forms (named H- and L-type BSE) have recently been described in Europe, Japan, and North America. Here we describe the first wide-spectrum microarray analysis in whole blood of atypical BSE-infected cattle. Transcriptome changes in infected animals were analyzed prior to and after the onset of clinical signs. The microarray analysis revealed gene expression changes in blood prior to the appearance of the clinical signs and during the progression of the disease. A set of 32 differentially expressed genes was found to be in common between clinical and preclinical stages and showed a very similar expression pattern in the two phases. A 22-gene signature showed an oscillating pattern of expression, being differentially expressed in the preclinical stage and then going back to control levels in the symptomatic phase. One gene, SEL1L3, was downregulated during the progression of the disease. Most of the studies performed up to date utilized various tissues, which are not suitable for a rapid analysis of infected animals and patients. Our findings suggest the intriguing possibility to take advantage of whole blood RNA transcriptional profiling for the preclinical identification of prion infection. Further, this study highlighted several pathways, such as immune response and metabolism that may play an important role in peripheral prion pathogenesis. Finally, the gene expression changes identified in the present study may be further investigated as a fingerprint for monitoring the progression of disease and for developing targeted therapeutic interventions. PMID

  9. Whole Blood Gene Expression Profiling in Preclinical and Clinical Cattle Infected with Atypical Bovine Spongiform Encephalopathy.

    Science.gov (United States)

    Xerxa, Elena; Barbisin, Maura; Chieppa, Maria Novella; Krmac, Helena; Vallino Costassa, Elena; Vatta, Paolo; Simmons, Marion; Caramelli, Maria; Casalone, Cristina; Corona, Cristiano; Legname, Giuseppe

    2016-01-01

    Prion diseases, such as bovine spongiform encephalopathies (BSE), are transmissible neurodegenerative disorders affecting humans and a wide variety of mammals. Variant Creutzfeldt-Jakob disease (vCJD), a prion disease in humans, has been linked to exposure to BSE prions. This classical BSE (cBSE) is now rapidly disappearing as a result of appropriate measures to control animal feeding. Besides cBSE, two atypical forms (named H- and L-type BSE) have recently been described in Europe, Japan, and North America. Here we describe the first wide-spectrum microarray analysis in whole blood of atypical BSE-infected cattle. Transcriptome changes in infected animals were analyzed prior to and after the onset of clinical signs. The microarray analysis revealed gene expression changes in blood prior to the appearance of the clinical signs and during the progression of the disease. A set of 32 differentially expressed genes was found to be in common between clinical and preclinical stages and showed a very similar expression pattern in the two phases. A 22-gene signature showed an oscillating pattern of expression, being differentially expressed in the preclinical stage and then going back to control levels in the symptomatic phase. One gene, SEL1L3, was downregulated during the progression of the disease. Most of the studies performed up to date utilized various tissues, which are not suitable for a rapid analysis of infected animals and patients. Our findings suggest the intriguing possibility to take advantage of whole blood RNA transcriptional profiling for the preclinical identification of prion infection. Further, this study highlighted several pathways, such as immune response and metabolism that may play an important role in peripheral prion pathogenesis. Finally, the gene expression changes identified in the present study may be further investigated as a fingerprint for monitoring the progression of disease and for developing targeted therapeutic interventions.

  10. Clinical profile of newly presenting diabetic patients at the University of Uyo Teaching Hospital, Nigeria

    International Nuclear Information System (INIS)

    Diabetes Mellitus is emerging as a major health challenge with the incidence and prevalence of the disease on the increase. It also contributes to overall morbidity and mortality with complications like cardiovascular disease, neuropathy, nephropathy, retinopathy and lower extremity amputation. There are few local studies on the clinical characteristics of the disease in our wet up and this study therefore set out to characterize the clinical profile of newly presenting diabetic patients in a health facility in Nigeria. It is a cross sectional, descriptive study carried out at the diabetes clinic of the University of Uyo Teaching Hospital between January 2007 and September 2008. Data obtained included age, sex, anthropometric indices, symptomatology, co-morbidities, complications and treatment of diabetes. Data was analyzed using SPSS version 10. A total of two hundred and seventy patients were studied (120 males, 150 females). About 89.2% were Type 2 DM patients and majority of the study subjects were overweight. Diabetic neuropathy was the commonest complication present in 38.8% of the subjects. Polyuria was the commonest symptom and hypertension the commonest comorbidity. Majority of the subjects were on oral hypolgycaemic agents for the management of their disease with the sulphonyureas and biguanides being the most common medication that was taken by them. A few of the patients were also taking herbal medication for treatment of their disease. Majority of the patients presenting in our facility have Type 2 diabetes, were hypertensive and overweight. Hypertension was the commonest co-morbidity and diabetic neuropathy the commonest complication. Adequate health education, subsidies on medications and proper funding of the health sector is necessary to stem the tide of the burden attributable to the disease. (author)

  11. Clinical profile of bronchiolitis in infants younger than 90 days in Saudi Arabia

    Directory of Open Access Journals (Sweden)

    Syed Amir Ahmad

    2014-01-01

    Full Text Available Background: Bronchiolitis is a self-limiting disease of children caused by viral infections of the small airways with a wide spectrum of illness severity. Search of the literature reveals a need for refinement of criteria for testing for concomitant severe bacterial infections as well as appropriate therapeutic interventions for patients <90-day-old diagnosed with clinical bronchiolitis. We believe that a better understanding of the disease spectrum will help optimize health-care delivery to these patients. Aims: The aim of this study was to determine the clinical profile at presentation, disease course and outcome of bronchiolitis in <3-month-old infants who presented to our Pediatric Emergency Department (PED during one disease season. Settings: Retrospective chart review during one bronchiolitis season, from November 1, 2011 to April 20, 2012. Subjects: All <90-day-old infants presenting with clinical bronchiolitis presenting to Urban PED of a tertiary care university hospital during one bronchiolitis season. Materials and Methods: A retrospective chart review based on computer records of all emergency department visits of infants less than 90 days with a clinical diagnosis of bronchiolitis, covering the period between November 1, 2011 and April 30, 2012. Results: Out of the total of 1895 infants <90 days of age, 141 had a clinical diagnosis of bronchiolitis and 35 needed admission to hospital. Blood for culture was obtained from 47 infants, urine for culture was obtained from 46 infants and cerebrospinal fluid for culture was obtained from eight infants. One case of bacteremia was documented, but this was found to be a contaminant. No cases of meningitis occurred among these infants. However, one infant had a positive urine culture consistent with infection (Escherichia coli . Conclusion: Based on the results, it can be conclude that the risk of bacteremia or meningitis among infants <90 days of age with fever and bronchiolitis is low. The

  12. Companion diagnostics and molecular imaging-enhanced approaches for oncology clinical trials.

    Science.gov (United States)

    Van Heertum, Ronald L; Scarimbolo, Robert; Ford, Robert; Berdougo, Eli; O'Neal, Michael

    2015-01-01

    In the era of personalized medicine, diagnostic approaches are helping pharmaceutical and biotechnology sponsors streamline the clinical trial process. Molecular assays and diagnostic imaging are routinely being used to stratify patients for treatment, monitor disease, and provide reliable early clinical phase assessments. The importance of diagnostic approaches in drug development is highlighted by the rapidly expanding global cancer diagnostics market and the emergent attention of regulatory agencies worldwide, who are beginning to offer more structured platforms and guidance for this area. In this paper, we highlight the key benefits of using companion diagnostics and diagnostic imaging with a focus on oncology clinical trials. Nuclear imaging using widely available radiopharmaceuticals in conjunction with molecular imaging of oncology targets has opened the door to more accurate disease assessment and the modernization of standard criteria for the evaluation, staging, and treatment responses of cancer patients. Furthermore, the introduction and validation of quantitative molecular imaging continues to drive and optimize the field of oncology diagnostics. Given their pivotal role in disease assessment and treatment, the validation and commercialization of diagnostic tools will continue to advance oncology clinical trials, support new oncology drugs, and promote better patient outcomes.

  13. Handbook of nuclear medicine and molecular imaging principles and clinical applications

    CERN Document Server

    Kim, Edmund E; Tateishi, Ukihide; Baum, Richard P

    2012-01-01

    This handbook will provide updated information on nuclear medicine and molecular imaging techniques as well as its clinical applications, including radionuclide therapy, to trainees and practitioners of nuclear medicine, radiology and general medicine. Updated information on nuclear medicine and molecular imaging are vitally important and useful to both trainees and existing practitioners. Imaging techniques and agents are advancing and changing so rapidly that concise and pertinent information are absolutely necessary and helpful. It is hoped that this handbook will help readers be better equipped for the utilization of new imaging methods and treatments using radiopharmaceuticals.

  14. Pfatp6 molecular profile of Plasmodium falciparum isolates in the western Brazilian Amazon

    Directory of Open Access Journals (Sweden)

    Brasil Larissa W

    2012-04-01

    Full Text Available Abstract Background Anti-malarial drug resistance has emerged as one of the biggest challenges confronting the worldwide effort to control malaria. The appearance of chloroquine and multi-drug resistance had devastating effects on therapeutic efficacy of former first-line agents. Artemisinin has proven to be an excellent therapeutic alternative to fill the void in chemotherapeutic options left by resistance mechanisms. At the time of introduction, no resistance to artemisinins had been recorded, and artemisinins demonstrated excellent parasite reduction rates. In an attempt to protect artemisinin efficacy, the World Health Organization (WHO made artemisinin-based combination therapy (ACT its official first-line treatment recommendation for uncomplicated Plasmodium falciparum in 2006. In Brazil, artemether/lumefantrine became the Brazilian Malaria Control Programme's official treatment recommendation in 2007. The sarco/endoplasmic reticulum Ca2+ - ATPase ortholog of P. falciparum (pfatp6 has been suggested as one of the targets of artemisinins. Consequently, pfatp6 gene polymorphisms are being investigated as markers of artemisinin resistance elsewhere. The goal of this work was to describe the molecular profile of pfatp6 in P. falciparum isolates from different localities in the Amazonas State. Methods DNA polymorphisms of the pfatp6 gene in 80 P. falciparum isolates from 11 municipalities of the Amazonas State (Western Brazilian Amazon, before and after the introduction of ACT in the Brazilian anti-malarial guidelines, were analysed by automatic sequencing. Mutations in the pfatp6 gene were searched using Mutation Surveyor v3.25 software. Results The P. falciparum pfatp6 gene presented polymorphisms at codons 37, 630 and 898. The R37K mutation was found in 16% of the samples, A630S in 32% and I898I in 52%. No S769N mutation, however, was detected in the analysed samples. Conclusion Despite the small number of samples, data presented here

  15. Molecular and Clinical Characteristics of Hospital and Community Onset Methicillin-Resistant Staphylococcus aureus Strains Associated with Bloodstream Infections

    OpenAIRE

    Wang, Shu-Hua; Hines, Lisa; van Balen, Joany; José R Mediavilla; Pan, Xueliang; Hoet, Armando E; Kreiswirth, Barry N.; Pancholi, Preeti; Stevenson, Kurt B.

    2015-01-01

    Methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections (BSI) are classified epidemiologically as health care-associated hospital onset (HAHO)-, health care-associated community onset (HACO)-, or community-associated (CA)-MRSA. Clinical and molecular differences between HAHO- and HACO-MRSA BSI are not well known. Thus, we evaluated clinical and molecular characteristics of MRSA BSI to determine if distinct features are associated with HAHO- or HACO-MRSA strains. Molecular ge...

  16. In vitro clinical trials: the future of cell-based profiling

    Directory of Open Access Journals (Sweden)

    Nathan T Ross

    2014-05-01

    Full Text Available The drug discovery process classically revolves around a set of biochemical and cellular assays to drive potency optimization and structural-activity relationship (SAR models. Layered on top of these concepts is the inclusion of molecular features that affect final drug use, things like: bioavailability, toxicity, stability, solubility, formulation, route of administration, etc. Paradoxically, most drugs entering clinical trials are only tested in a handful of human genetic backgrounds before they are given to people. Here we review efforts and opine on the use of large scale in vitro cellular and in vivo models that attempt to model human disease and include diversity found in the human genetic population. Because hundreds to thousands of individual assays are needed to scratch the surface of human genetic diversity, sophisticated high throughput automation technologies or pooling & deconvolution strategies are required. Characterization of each model needs to be extensive to enable non-biased informatics based modeling. Such approaches will enable deep understanding of genetic to pharmacological response and result in new methods for patient stratification in the clinic. Oncology medicines and cancer genetics have been paving the way for these approaches and we expect to see continued expansion to other fields such as immunology and neuroscience.

  17. Molecular detection of virulence factors among food and clinical Enterococcus faecalis strains in South Brazil.

    Science.gov (United States)

    Medeiros, A W; Pereira, R I; Oliveira, D V; Martins, P D; d'Azevedo, P A; Van der Sand, S; Frazzon, J; Frazzon, A P G

    2014-01-01

    The present report aimed to perform a molecular epidemiological survey by investigating the presence of virulence factors in E. faecalis isolated from different human clinical (n = 57) and food samples (n = 55) in Porto Alegre, Brazil, collected from 2006 to 2009. In addition, the ability to form biofilm in vitro on polystyrene and the β-haemolytic and gelatinase activities were determined. Clinical strains presented a higher prevalence of aggregation substance (agg), enterococcal surface protein (esp) and cytolysin (cylA) genes when compared with food isolates. The esp gene was found only in clinical strains. On the other hand, the gelatinase (gelE) and adherence factor (ace) genes had similar prevalence among the strains, showing the widespread occurrence of these virulence factors among food and clinical E. faecalis strains in South Brazil. More than three virulence factor genes were detected in 77.2% and 18.2% of clinical and food strains, respectively. Gelatinase and β-haemolysin activities were not associated with the presence of gelE and cylA genes. The ability to produce biofilm was detected in 100% of clinical and 94.6% of food isolates, and clinical strains were more able to form biofilm than the food isolates (Student's t-test, p detected in clinical strains.

  18. DataGenno: building a new tool to bridge molecular and clinical genetics

    Directory of Open Access Journals (Sweden)

    Fabricio F Costa

    2011-03-01

    Full Text Available Fabricio F Costa1,2, Luciano S Foly1, Marcelo P Coutinho11DataGenno Interactive Research Ltd., Itaperuna, Rio de Janeiro, Brazil; 2Cancer Biology and Epigenomics Program, Children's Memorial Research Center, Northwestern University's Feinberg School of Medicine, Chicago, IL, USAAbstract: Clinical genetics is one of the most challenging fields in medicine, with thousands of children born every year with congenital defects that have no satisfactory diagnosis. There are more than 6,000 known single-gene disorders that can cause birth defects or diseases in approximately 1 in every 200 births. Clinical and molecular information on genetic diseases and syndromes are widespread in the literature, and there are few databases combining this information. Therefore, it is very challenging for health care professionals and researchers to translate the latest advances in science and medicine into effective clinical interventions and new treatments. In order to overcome this obstacle and promote networking, we are building DataGenno, an online medical and scientific portal. DataGenno has been developed to be a source of information on genetic diseases and syndromes for the needs of all heath care professionals and researchers. Our database will be able to integrate both clinical and molecular aspects of genetic diseases in a fully interactive environment. DataGenno’s system already contains clinical and molecular information for 300 diseases, with approximately 6,000 signs and symptoms of these diseases in a database combined with a search engine. Our main goal is to cover all genetic diseases described to date, providing not only clinical information such as morphological and anatomical features but also the most comprehensive molecular genetics/genomics features and available testing information. We are also developing ways to connect DataGenno’s portal with Electronic Health Records in order to improve the efficiency of patient care. Additionally

  19. Inflammatory therapeutic targets in coronary atherosclerosis – from molecular biology to clinical application

    Directory of Open Access Journals (Sweden)

    Fabian eLinden

    2014-11-01

    Full Text Available Atherosclerosis is the leading cause of death worldwide. Over the past two decades, it has been clearly recognized that atherosclerosis is an inflammatory disease of the arterial wall. Accumulating data from animal experiments have supported this hypothesis, however, clinical applications making use of this knowledge remain scarce. In spite of optimal interventional and medical therapy, the risk for recurrent myocardial infarction remains by about 20% over three years after acute coronary syndromes, novel therapies to prevent atherogenesis or treat atherosclerosis are urgently needed. This review summarizes selected potential molecu-lar inflammatory targets that may be of clinical relevance. We also review recent and ongoing clinical trails that target inflammatory processes aiming at preventing adverse cardiovascular events. Overall, it seems surprising that translation of basic science into clinical practice has not been a great success. In conclusion, we propose to focus on specific efforts that promote translational science in order to improve outcome and prognosis of patients suffering from atherosclerosis.

  20. Clinical and psychoeducational profile of children with specific learning disability and co-occurring attention-deficit hyperactivity disorder

    OpenAIRE

    Karande Sunil; Satam Nitin; Kulkarni Madhuri; Sholapurwala Rukhshana; Chitre Anita; Shah Nilesh

    2007-01-01

    Background: Almost 10% of school-going children have specific learning disability (SpLD) in the form of dyslexia, dysgraphia and/ or dyscalculia. Attention-deficit hyperactivity disorder (ADHD) occurs as a comorbidity in about 20% of these children. Aims: To document the clinical profile and academic history of children with SpLD and co-occurring ADHD. Settings and Design: Prospective observational study conducted in our clinic. Materials and Methods: From August to November 200...

  1. Clinical Profile, Co-Morbidities and Health Related Quality of Life in Pediatric Patients with Allergic Rhinitis and Asthma

    OpenAIRE

    Keya R. Lahiri, Milind S. Tullu* and Rachna Kalra

    2010-01-01

    Background: Co-existence of allergic rhinitis (AR) and bronchial asthma (BA) is well known. We planned to study the clinical profile of patients with AR & BA, the associated co-morbidities and the effect of AR &/ or BA on health related quality of life (HRQOL) in Pediatric patients. Methods: Patients attending the Pediatric out-patients department and Pediatric Chest Clinic of tertiary care center were enrolled. The sample size included 100 subjects with BA & AR (Group 1) with control groups ...

  2. Bladder Carcinoma Data with Clinical Risk Factors and Molecular Markers: A Cluster Analysis

    Directory of Open Access Journals (Sweden)

    Enrique Redondo-Gonzalez

    2015-01-01

    Full Text Available Bladder cancer occurs in the epithelial lining of the urinary bladder and is amongst the most common types of cancer in humans, killing thousands of people a year. This paper is based on the hypothesis that the use of clinical and histopathological data together with information about the concentration of various molecular markers in patients is useful for the prediction of outcomes and the design of treatments of nonmuscle invasive bladder carcinoma (NMIBC. A population of 45 patients with a new diagnosis of NMIBC was selected. Patients with benign prostatic hyperplasia (BPH, muscle invasive bladder carcinoma (MIBC, carcinoma in situ (CIS, and NMIBC recurrent tumors were not included due to their different clinical behavior. Clinical history was obtained by means of anamnesis and physical examination, and preoperative imaging and urine cytology were carried out for all patients. Then, patients underwent conventional transurethral resection (TURBT and some proteomic analyses quantified the biomarkers (p53, neu, and EGFR. A postoperative follow-up was performed to detect relapse and progression. Clusterings were performed to find groups with clinical, molecular markers, histopathological prognostic factors, and statistics about recurrence, progression, and overall survival of patients with NMIBC. Four groups were found according to tumor sizes, risk of relapse or progression, and biological behavior. Outlier patients were also detected and categorized according to their clinical characters and biological behavior.

  3. Molecular physiology of cellular glucose transport - a potential area for clinical studies in diabetes mellitus.

    Science.gov (United States)

    Tatoń, Jan; Piatkiewicz, Paweł; Czech, Anna

    2010-01-01

    The normalization of cellular glucose assimilation is the basic aim of metabolic therapy in type 2 diabetes mellitus (T2DM). It requires parallel changes in the process of cellular glucose transport (CGT). This review presents the pathophysiological and clinical outlines of CGT. Sequentially, the advances in the mechanisms and classification of CGT and their physiological and molecular base are described. The role of CGT pathogenetic significance in diabetes mellitus is stressed. Finally, the opinion is expressed that the CGT study is a potentially important approach to clinical interpretation of glucose metabolism disturbances and their pharmacotherapy. PMID:20602306

  4. Clinical and Molecular Phenotype of Aicardi-Goutières Syndrome

    OpenAIRE

    Rice, Gillian ; Patrick, Teresa ; Parmar, Rekha ; Taylor, Claire F. ; Aeby, Alec ; Aicardi, Jean ; Artuch, Rafael ; Montalto, Simon Attard ; Bacino, Carlos A. ; Barroso, Bruno ; Baxter, Peter ; Benko, Willam S. ; Bergmann, Carsten ; Bertini, Enrico ; Biancheri, Roberta 

    2007-01-01

    Aicardi-Goutières syndrome (AGS) is a genetic encephalopathy whose clinical features mimic those of acquired in utero viral infection. AGS exhibits locus heterogeneity, with mutations identified in genes encoding the 3′→5′ exonuclease TREX1 and the three subunits of the RNASEH2 endonuclease complex. To define the molecular spectrum of AGS, we performed mutation screening in patients, from 127 pedigrees, with a clinical diagnosis of the disease. Biallelic mutations in TREX1, RNASEH2A, RNASEH2B...

  5. A prospective study of reversible dementias: Frequency, causes, clinical profile and results of treatment

    Directory of Open Access Journals (Sweden)

    Srikanth S

    2005-01-01

    Full Text Available Background: Dementia due to potentially reversible etiologies is an important group of dementias to be identified not only because of the number of such Patients encountered but also due to the potential for substantial improvement with treatment. Aims : To prospectively investigate the frequency and causes of dementias with potentially reversible etiologies; to examine the clinical features of this subgroup with a view to identifying a signature profile and to determine if this potential reversibility translates into actual reversibility with appropriate treatment. Setting and design : A prospective longitudinal study of patients with dementia presenting to the outpatient services of a tertiary referral hospital. Methods : All Patients above 40 years referred for evaluation of cognitive complaints were serially enrolled and underwent clinical examination, various laboratory tests and neuroimaging. Patients were followed-up for one year. Statistical analysis : One way analysis of variance for continuous variables followed by post hoc comparisons using Scheffe′s procedure. Results: A total of 129 patients met Diagnostic and Statistical Manual of Mental Disorders edition 4 (DSM IV criteria for dementia and qualified for inclusion into the study. Twenty-four patients (18%, all with moderately severe cognitive [mean mini mental state examination (MMSE score ± SD = 17.9 ± 4.8] and neuropsychiatric [mean neuropsychiatric inventory (NPI score ± SD = 30.7 ± 8.7] dysfunction were diagnosed to have reversible causes - neuroinfections in 11 patients, normal pressure hydrocephalus in 8 patients and vitamin B12 deficiency in 5 patients. The majority of these patients had gait and urinary dysfunction reminiscent of subcortical dementias. These reversible causes were clinically suspected in only 58% of patients. In 20/24 patients in whom follow up was possible mean MMSE score had improved to 22.2 and mean NPI score had improved to 8.0, following 6 months

  6. Spinal and cutaneous schwannomatosis is a variant form of type 2 neurofibromatosis: a clinical and molecular study.

    OpenAIRE

    Evans, D. G.; Mason, S; Huson, S M; Ponder, M.; Harding, A E; Strachan, T

    1997-01-01

    OBJECTIVE: To delineate the clinical phenotype, molecular basis, and implications for screening in patients and families with multiple schwannomas not generally involving the cranium. METHODS: As part of a United Kingdom clinical and genetic study of type 2 neurofibromatosis (NF2) patients and families with multiple schwannomas who do not fulfil diagnostic criteria for NF2 have been identified. The clinical phenotype was studied in the extended families and molecular analysis was carried out ...

  7. Glioma-related edema: new insight into molecular mechanisms and their clinical implications

    Institute of Scientific and Technical Information of China (English)

    Zhi-Xiong Lin

    2013-01-01

    Glioma-related edema (GRE) is a significant contributor to morbidity and mortality from glioma.GRE is a complicated process involving not only peritumoral edema but also the water content of the tumor body.In terms of etiology,this condition derives from both GRE in the untreated state and GRE secondary to clinical intervention,and different cell types contribute to distinct components of GRE.Peritumoral edema was previously believed to loosen glioma tissue,facilitating tumor-cell invasion;however,the nutrition hypothesis of the tumor microecosystem suggests that tumor cells invade for the sake of nutrition.Edema is the pathologic consequence of the reconstructed trophic linkage within the tumor microecosystem.Glioma cells induce peritumoral brain edema via an active process that supplies a suitable niche for peritumoral invasive cells,suggesting that glioma-related peritumoral brain edema is determined by the invasive property of tumor cells.There are differences between pivotal molecular events and reactive molecular events in the development of GRE.Molecular therapy should target the former,as targeting reactive molecular events will produce undesired or even adverse results.At present,brain glioma angiogenesis models have not been translated into a new understanding of the features of brain images.The effect of these models on peritumoral brain edema is unclear.Clinical approaches should be transformed on the basis of new knowledge of the molecular mechanism underlying GRE.Exploring clinical assessment methods,optimizing the existing control strategy of GRE,and simultaneously developing new treatments are essential.

  8. Integrative genome-wide expression profiling identifies three distinct molecular subgroups of renal cell carcinoma with different patient outcome

    International Nuclear Information System (INIS)

    Renal cell carcinoma (RCC) is characterized by a number of diverse molecular aberrations that differ among individuals. Recent approaches to molecularly classify RCC were based on clinical, pathological as well as on single molecular parameters. As a consequence, gene expression patterns reflecting the sum of genetic aberrations in individual tumors may not have been recognized. In an attempt to uncover such molecular features in RCC, we used a novel, unbiased and integrative approach. We integrated gene expression data from 97 primary RCC of different pathologic parameters, 15 RCC metastases as well as 34 cancer cell lines for two-way nonsupervised hierarchical clustering using gene groups suggested by the PANTHER Classification System. We depicted the genomic landscape of the resulted tumor groups by means of Single Nuclear Polymorphism (SNP) technology. Finally, the achieved results were immunohistochemically analyzed using a tissue microarray (TMA) composed of 254 RCC. We found robust, genome wide expression signatures, which split RCC into three distinct molecular subgroups. These groups remained stable even if randomly selected gene sets were clustered. Notably, the pattern obtained from RCC cell lines was clearly distinguishable from that of primary tumors. SNP array analysis demonstrated differing frequencies of chromosomal copy number alterations among RCC subgroups. TMA analysis with group-specific markers showed a prognostic significance of the different groups. We propose the existence of characteristic and histologically independent genome-wide expression outputs in RCC with potential biological and clinical relevance

  9. Cryptosporidium infection in ostriches (Struthio camelus in Brazil: clinical, morphological and molecular studies

    Directory of Open Access Journals (Sweden)

    MMAB Santos

    2005-06-01

    Full Text Available Avian cryptosporidiosis has been reported in more than 30 species of birds. To date, the species infecting birds are C. baileyi, C. galli and C. meleagridis. In this study, the morphological, clinical and molecular characteristics of a Brazilian ostrich isolate of Cryptosporidium are described. The oocysts of this Brazilian isolate are larger and more elongated than those of Cryptosporidium previously reported in ostriches, which were morphologically similar to C. meleagridis. Morphological, biological and molecular analyses demonstrated similarity of this ostrich isolate with C. baileyi, suggesting that there are at least two Cryptosporidium species infecting ostriches; one with molecular, biological and morphological characteristics related to C. baileyi, and another morphologically similar to C. meleagridis.

  10. Clinical and Molecular Characterization of Patients with Mucopolysaccharidosis Type I in an Algerian Series

    Directory of Open Access Journals (Sweden)

    Abdellah Tebani

    2016-05-01

    Full Text Available Mucopolysaccharidoses (MPS’s represent a subgroup of lysosomal storage diseases related to a deficiency of enzymes that catalyze glycosaminoglycans degradation. Mucopolysaccharidosis type I (MPS I is a rare autosomal recessive disorder caused by a deficiency of α-l-iduronidase encoded by the IDUA gene. Partially degraded heparan sulfate and dermatan sulfate accumulate progressively and lead to multiorgan dysfunction and damage. The aim of this study is to describe the clinical, biochemical, and molecular characteristics of 13 Algerian patients from 11 distinct families. MPS I diagnosis was confirmed by molecular study of the patients’ IDUA gene. Clinical features at the diagnosis and during the follow-up are reported. Eighty-four percent of the studied patients presented with a mild clinical phenotype. Molecular study of the IDUA gene allowed the characterization of four pathological variations at the homozygous or compound heterozygote status: IDUA NM_00203.4:c.1598C>G-p.(Pro533Arg in 21/26 alleles, IDUA NM_00203.4:c.532G>A-p.(Glu178Lys in 2/26 alleles, IDUA NM_00203.4:c.501C>G-p.(Tyr167* in 2/26 alleles, and IDUA NM_00203. 4: c.1743C>G-p.(Tyr581* in 1/26 alleles. This molecular study unveils the predominance of p.(Pro533Arg variation in our MPS I patients. In this series, the occurrence of some clinical features linked to the Scheie syndrome is consistent with the literature, such as systematic valvulopathies, corneal opacity, and umbilical hernia; however, storage signs, facial dysmorphic features, and hepatomegaly were more frequent in our series. Screening measures for these debilitating diseases in highly consanguineous at-risk populations must be considered a priority health problem.

  11. Clinical and Molecular Characterization of Patients with Mucopolysaccharidosis Type I in an Algerian Series.

    Science.gov (United States)

    Tebani, Abdellah; Zanoutene-Cheriet, Lahouaria; Adjtoutah, Zoubir; Abily-Donval, Lenaig; Brasse-Lagnel, Carole; Laquerrière, Annie; Marret, Stephane; Chalabi Benabdellah, Abla; Bekri, Soumeya

    2016-01-01

    Mucopolysaccharidoses (MPS's) represent a subgroup of lysosomal storage diseases related to a deficiency of enzymes that catalyze glycosaminoglycans degradation. Mucopolysaccharidosis type I (MPS I) is a rare autosomal recessive disorder caused by a deficiency of α-l-iduronidase encoded by the IDUA gene. Partially degraded heparan sulfate and dermatan sulfate accumulate progressively and lead to multiorgan dysfunction and damage. The aim of this study is to describe the clinical, biochemical, and molecular characteristics of 13 Algerian patients from 11 distinct families. MPS I diagnosis was confirmed by molecular study of the patients' IDUA gene. Clinical features at the diagnosis and during the follow-up are reported. Eighty-four percent of the studied patients presented with a mild clinical phenotype. Molecular study of the IDUA gene allowed the characterization of four pathological variations at the homozygous or compound heterozygote status: IDUA NM_00203.4:c.1598C>G-p.(Pro533Arg) in 21/26 alleles, IDUA NM_00203.4:c.532G>A-p.(Glu178Lys) in 2/26 alleles, IDUA NM_00203.4:c.501C>G-p.(Tyr167*) in 2/26 alleles, and IDUA NM_00203. 4: c.1743C>G-p.(Tyr581*) in 1/26 alleles. This molecular study unveils the predominance of p.(Pro533Arg) variation in our MPS I patients. In this series, the occurrence of some clinical features linked to the Scheie syndrome is consistent with the literature, such as systematic valvulopathies, corneal opacity, and umbilical hernia; however, storage signs, facial dysmorphic features, and hepatomegaly were more frequent in our series. Screening measures for these debilitating diseases in highly consanguineous at-risk populations must be considered a priority health problem. PMID:27196898

  12. Molecular Typing of Borrelia burgdorferi Sensu Lato: Taxonomic, Epidemiological, and Clinical Implications

    OpenAIRE

    Wang, Guiqing; Dam, Alje P. van; Schwartz, Ira; Dankert, Jacob

    1999-01-01

    Borrelia burgdorferi sensu lato, the spirochete that causes human Lyme borreliosis (LB), is a genetically and phenotypically divergent species. In the past several years, various molecular approaches have been developed and used to determine the phenotypic and genetic heterogeneity within the LB-related spirochetes and their potential association with distinct clinical syndromes. These methods include serotyping, multilocus enzyme electrophoresis, DNA-DNA reassociation analysis, rRNA gene res...

  13. Leber's hereditary optic neuropathy with late disease onset: clinical and molecular characteristics of 20 patients

    OpenAIRE

    Dimitriadis, Konstantin; Leonhardt, Miriam; Yu-Wai-Man, Patrick; Kirkman, Matthew Anthony; Korsten, Alex; De Coo, Irenaeus F; Chinnery, Patrick Francis; Klopstock, Thomas

    2014-01-01

    Background: Leber's hereditary optic neuropathy (LHON) is a mitochondrial disease that typically causes bilateral blindness in young men. Here we describe the clinical and molecular characteristics of 20 patients with disease onset after the age of 50 years (late onset-LHON). Methods: From a cohort of 251 affected and 277 unaffected LHON carriers, we identified 20 patients with onset of visual loss after the age of 50 years. Using structured questionnaires, data including basic demographic de...

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

    OpenAIRE

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

    2016-01-01

    The receptor tyrosine kinase AXL is a member of the Tyro3-Axl-Mer receptor tyrosine kinase subfamily. AXL affects several cellular functions, including growth and migration. AXL aberration is reportedly a marker for poor prognosis and treatment resistance in various cancers. In this study, we analyzed clinical, pathological, and molecular features of AXL expression in lung adenocarcinomas (LADs). We examined 161 LAD specimens from patients who underwent pulmonary resections. When AXL protein ...

  15. Clinical profile of dengue fever infection in patients admitted in tertiary care centre Agroha, Hisar, Haryana, India

    Directory of Open Access Journals (Sweden)

    Mohd Younus Shah

    2016-06-01

    Conclusions: Significant differences in the clinical profile is possibly because of infection with different serotypes of dengue virus (DENV, concurrent/sequential infection of more than one serotype, and differences in host immune responses associated with host genetic variations. [Int J Res Med Sci 2016; 4(6.000: 2146-2149

  16. Differential intragraft cytokine messenger RNA profiles during rejection and repair of clinical heart transplants. A longitudinal study

    NARCIS (Netherlands)

    de Groot-Kruseman, Hester A; Mol, Wendy M; Niesters, Hubert G M; Maat, Alex P W; van Gelder, Teun; Balk, Aggie H M M; Weimar, Willem; Baan, Carla C

    2003-01-01

    After clinical heart transplantation, ischemia, acute rejection, and repair mechanisms can trigger the up-regulation of cytokines. To investigate the cytokine profile early after transplantation, we monitored messenger RNA (mRNA) expression levels of tumor necrosis factor-alpha (TNF-alpha), monocyte

  17. Replacement of asymmetric synaptic profiles in the molecular layer of dentate gyrus following cycloheximide in the pilocarpine model in rats.

    Directory of Open Access Journals (Sweden)

    Simone eBittencourt

    2015-11-01

    Full Text Available Mossy fiber sprouting is among the best-studied forms of post-lesional synaptic plasticity and is regarded by many as contributory to seizures in both humans and animal models of epilepsy. It is not known whether mossy fiber sprouting increases the number of synapses in the molecular layer or merely replaces lost contacts. Using the pilocarpine model of status epilepticus to induce mossy fiber sprouting, and cycloheximide to block this sprouting, we evaluated at the ultrastructural level the number and type of asymmetric synaptic contacts in the molecular layer of the dentate gyrus. As expected, whereas pilocarpine-treated rats had dense silver grain deposits in the inner molecular layer (reflecting mossy fiber sprouting, pilocarpine+cycloheximide-treated animals did not differ from controls. Both groups of treated rats (Pilo group and CHX+Pilo group had reduced density of asymmetric synaptic profiles (putative excitatory synaptic contacts, which was greater for cycloheximide-treated animals. For both treated groups the loss of excitatory synaptic contacts was even greater in the outer molecular layer than in the best studied inner molecular layer (in which mossy fiber sprouting occurs. These results indicate that mossy fiber sprouting tends to replace lost synaptic contacts rather than increase the absolute number of contacts. We speculate that the overall result is more consistent with restored rather than with increased excitability.

  18. Early-onset gastric cancers have a different molecular expression profile than conventional gastric cancers

    NARCIS (Netherlands)

    A.N.A. Milne; R. Carvalho; F.M. Morsink; A.R. Musler; W.W.J. de Leng; A. Ristimaki; G.J.A. Offerhaus

    2006-01-01

    Many studies examine the molecular genetics of gastric cancer, but few look at young patients in particular and there is no comparison of molecular expression between early-onset gastric cancer (<= 45 years old) and conventional gastric cancers. Expression of cycloxygenase-2 (COX-2) is elevated in g

  19. Histological Stratification of Thick and Thin Plaque Psoriasis Explores Molecular Phenotypes with Clinical Implications.

    Directory of Open Access Journals (Sweden)

    Jaehwan Kim

    Full Text Available Psoriasis, which presents as red, scaly patches on the body, is a common, autoimmune skin disease that affects 2 to 3 percent of the world population. To leverage recent molecular findings into the personalized treatment of psoriasis, we need a strategy that integrates clinical stratification with molecular phenotyping. In this study, we sought to stratify psoriasis patients by histological measurements of epidermal thickness, and to compare their molecular characterizations by gene expression, serum cytokines, and response to biologics. We obtained histological measures of epidermal thickness in a cohort of 609 psoriasis patients, and identified a mixture of two subpopulations-thick and thin plaque psoriasis-from which they were derived. This stratification was verified in a subcohort of 65 patients from a previously published study with significant differences in inflammatory cell infiltrates in the psoriatic skin. Thick and thin plaque psoriasis shared 84.8% of the meta-analysis-derived psoriasis transcriptome, but a stronger dysregulation of the meta-analysis-derived psoriasis transcriptome was seen in thick plaque psoriasis on microarray. RT-PCR revealed that gene expression in thick and thin plaque psoriasis was different not only within psoriatic lesional skin but also in peripheral non-lesional skin. Additionally, differences in circulating cytokines and their changes in response to biologic treatments were found between the two subgroups. All together, we were able to integrate histological stratification with molecular phenotyping as a way of exploring clinical phenotypes with different expression levels of the psoriasis transcriptome and circulating cytokines.

  20. Microbiological profile and clinical outcome of severe foot ulcers of diabetic inpatients

    Directory of Open Access Journals (Sweden)

    Marivaldo Loyola Aragão(

    2010-09-01

    Full Text Available Objectives: To describe the microbiological profile and clinical outcomes of diabetic foot ulcers of inpatients of a tertiary university hospital, at Ceara, Brazil. Methods: We conducted a retrospective analysis of medical charts data of all diabetic inpatients of the Endocrine and Diabetes Unit of Walter Cantídio University Hospital (Federal University of Ceará, admitted from January, 2006 to June, 2007 for severe foot ulcers (minimum of grade 2 of Wagner`s classification, which were refractory to ambulatory treatment. Clinical data from each patient were recorded (sex, age, diabetes duration, and comorbidities as well as microbiological characteristics of foot ulcers and surgical (amputations material. Results: We identified 17 diabetic patients, all type 2, aged 58.11 ± 10.8 years and 12.4 ± 8.4 years of disease, 58.8% male. Of ulcers, 41.1% were grade 2; 35.2% grade 3; 11.7% grade 4 and 11.7% grade 5 of Wagner; 64.7% with less than 3 months of evolution. Debridement was performed in 82.3% of patients and amputation in 47%; osteomyelitis was identified in 47% of cases. All patients started empiric antibiotic therapy, where ciprofloxacin/metronidazole was the most used scheme (76.5%. Cultures were negative in 12.5% of the patients. In the positive ones, the most prevalent bacterial pathogens detected in the culture materials were: S. aureus (57.1%; S. viridans (28.7%; P. aeruginosas (28.7%; M. morganii (28.7%. The majority (75% of isolated S. aureus were methicillin-resistant, but were sensitive to vacomicin. Conclusion: We observed the presence of polymicrobial flora with a large number of multiresistant pathogens and high prevalence of osteomyelitis and amputations in diabetic patients with severe ulcers, neuropathy and peripheral vascular disease.

  1. A Study of Socio Demographic and Clinical Profile of Cases of Diabetic Foot

    Directory of Open Access Journals (Sweden)

    Jayesh B Gohel

    2012-06-01

    Full Text Available Introduction: Diabetic foot is a complication of Diabetes Mellitus, which is a group of metabolic disorders sharing the phenotype of hyperglycemia. The aim of the therapy is to avoid diabetic foot complications, salvage the limb with available modalities in hospital, preventing recurrences and rehabilitation. Methods: This article summarizes the profile of 200 patients with diabetic foot seen in General Surgery department of Civil Hospital at Ahmedabad. The diagnosis of diabetic foot was based on clinical, biochemical and radiological investigations. Clinical presentation can be divided into infective, vascular and neuropathic groups. Results: Average age of presentation was 55.02 year. There is a higher incidence in male patients, majority of patients (57% belongs to lower socioeconomic status. The average duration of diabetes is 9.78 years. Severity of lesion correlated with severity and duration of diabetes. Commonest presenting feature is an abscess followed by gangrene. Staph.aureus is the most common organism isolated from diabetic foot. X-Rays of feet were taken and majority presented with osteomyelitic changes. The average duration of hospital stay was 17.34 days. Conclusion: Foot ulceration in diabetic patients is a resource consuming, disabling morbidity that often is the first step towards lower extremity amputation. Prevention is the best treatment. Effective glycemic control and education are of key importance for decreasing diabetic foot disease, while early presentation and hospital admission, aggressive and appropriate medical and surgical treatment according to grade if disease can improve outcome and reduce the morbidity and mortality due to diabetes. [National J of Med Res 2012; 2(3.000: 279-281

  2. MYOCARDIAL BRIDGING - CLINICAL AND ANGIOGRAPHIC PROFILE IN LAST 5 YEARS; A STUDY OF 129 CASES

    Directory of Open Access Journals (Sweden)

    Abhilash S P

    2010-11-01

    Full Text Available Aims of study : To assess the clinical and angiographical profile of myocardial bridging from consecutive coronary angiograms done over last 5 years at Medical college, Thiruvananthapuram. To assess the risk of cardiovascular events and the risk of accelerated atherosclerosis in isolated myocardial bridging. Methods : Consecutive coronary angiograms done at Medical college Thiruvananthapuram from 04/02/2005 to 31/03/2010 were reviewed for myocardial bridging. A total of 10492 coronary angiograms were reviewed. Myocardial bridges with systolic lumen reduction of more than 50% were considered for analysis. Quantitative coronary angiography (QCA was used for analysis. Clinical presentation as well as correlation with structural heart disease and coronary heart disease was assessed. Results: Incidence of myocardial bridges was 1.23%. Of the 129 patients with myocardial bridges 63 ( 48.8% had associated significant coronary artery disease. Remaining 66 (51.2% patients presented with isolated bridges. Out of these 66 patients with isolated myocardial bridges, 7 (10.6% patients presented with acute myocardial infarction and 3 (4.5% presented with cardiac arrhythmias. Of the 63 patients with significant coronary disease 11 (17.5% patients had single vessel disease and they had the culprit lesion and myocardial bridge seen in the same vessel. Most common location of myocardial bridge was mid LAD (64.9% followed by distal LAD (23.8%. Length of bridge was 20 mm in 35.7%. Mean percentage of systolic obliteration by the bridge was 74.5%. 100% systolic obliteration was seen in 7.79% of isolated bridges and in 9.79% of bridges with CAD. Among 120 rhuematic heart disease patients who underwent coronary angiogram, 10 (8.3% patients had myocardial bridging. 12.1% of all HCM patients who underwent coronary angiograms had myocardial bridging. Conclusion: Myocardial bridging can be lethal- can accelerate atherosclerosis, can precipitate acute MIs and life

  3. Clinical, Laboratory and Bacterial Profile of Spontaneous Bacterial Peritonitis in Chronic Liver Disease Patients

    International Nuclear Information System (INIS)

    Objective: To determine the clinical and laboratory features, bacterial profile and antibiotic sensitivity pattern of Spontaneous Bacterial Peritonitis (SBP) in Chronic Liver Disease (CLD) patients presenting at a tertiary care hospital of Karachi. Study Design: Cross-sectional study. Place and Duration of Study: PMRC Centre for Gastroenterology and Hepatology and Jinnah Postgraduate Medical Centre, Karachi, from April 2010 to March 2012. Methodology: CLD patients with ascites were recruited from PMRC Centre for Gastroenterology and Hepatology and Jinnah Postgraduate Medical Centre, Karachi. Basic demographics, symptoms and clinical signs of patients were recorded. Patients with the history of antibiotic use within last 3 days or any intra-abdominal source of infection were excluded. Diagnostic paracentesis was done for ascitic fluid detailed report (D/R) and culture. Blood sample was collected for total leukocyte count, serum proteins and billirubin levels. Results: Out of a total 152 CLD patients, 38 (25%) were diagnosed with SBP. Eight (24.2%) patients presented with classical SBP, 20 (52.6%) had culture negative neutrocytic ascites and 10 (26%) had bacterascites. Fever, abdominal tenderness and constipation were common in SBP patients. Ascitic fluid culture was positive in 19 (50%) patients. E. coli (65%) was the predominant pathogen followed by Enterococcus species (15%). Resistance was high against cephalosporins (78%) and fluoroquinolones (69.6%) and least against amikacin (13%) and meropenem (12%). Conclusion: Ascitic fluid D/R and culture together can lead to the accurate diagnosis of SBP and can guide for the right antibiotic choice as resistance to commonly prescribed antibiotic is common in such patients. (author)

  4. THE STUDY OF PREVALENCE AND CLINICAL PROFILE OF VALVULAR HEART DISEASES IN A TEACHING HOSPITAL

    Directory of Open Access Journals (Sweden)

    Radha Krishnan

    2015-04-01

    Full Text Available Valvular heart disease is still a common causes of mortality and morbidity in India and rheumatic heart disease is still far more frequent. AIMS AND OBJECTIVES: To study the prevalence and clinical profile of rheumatic and non - rheumatic valvular heart dise ase in patients attending to Government General Hospital, Kakinada. MATERIALS AND METHODS: 100 Adult patients with valvular abnormalities attending to the Medicine and Cardiology Units of Government General Hospital, Kakinada from Nov 2011 - May 2013 were studied. C linical history including various symptoms, past history of rheumatic fever, followed by systemic examination was done. A detailed cardiovascular examination with relevant investigations and evaluation was done. OBSERVATIONS AND RESULTS: The most common cause of acquired valvular heart disease is Rheumatic Heart Disease. Mitral valve involvement is the most common valve involvement with Mitral regurgitation as the most common valvular lesion. Mitral stenosis is the most common valvular lesion amon g rheumatic valvular heart disease. The most common complaint is breathlessness and the most common complication is Congestive heart failure. Multi valvular lesion is the most common valve involvement in patients presenting with congestive heart failure an d infective endocarditis. Patients having atrial fibrillation are noted to have mitral stenosis more commonly. Mitral stenosis is the valve abnormality commonly noted in patients presenting with haemoptysis, respiratory tract infection and chorea. Left sid ed hemiplegia is common in patients with acquired valvular heart disease. CONCLUSIONS: Though the incidencen of rheumatic valvular disease is decreased in modern era, still continuing in our country. The analysis of the present study gives us insight into the various types of presentation of acquired valvular heart disease and to increase awareness besides early detection of valvular diseases clinically. It also helps in planning of

  5. Refractory myasthenia gravis – clinical profile, comorbidities and response to rituximab

    Science.gov (United States)

    Sudulagunta, Sreenivasa Rao; Sepehrar, Mona; Sodalagunta, Mahesh Babu; Settikere Nataraju, Aravinda; Bangalore Raja, Shiva Kumar; Sathyanarayana, Deepak; Gummadi, Siddharth; Burra, Hemanth Kumar

    2016-01-01

    Introduction: Myasthenia gravis (MG) is an antibody mediated autoimmune neuromuscular disorder characterized by fatigable muscle weakness. A proportion of myasthenia gravis patients are classified as refractory due to non responsiveness to conventional treatment. This retrospective study was done to evaluate clinical profile, epidemiological, laboratory, and features of patients with MG and mode of management using rituximab and complications. Methods: Data of myasthenia gravis patients admitted or presented to outpatient department (previous medical records) with MG between January 2008 and January 2016 were included. A total of 512 patients fulfilled the clinical and diagnostic criteria of myasthenia gravis of which 76 patients met the diagnostic certainty for refractory myasthenia gravis and were evaluated. Results: Out of 76 refractory MG patients, 53 (69.73%) patients fulfilled all the three defined criteria. The median age of onset of the refractory MG group was 36 years with a range of 27–53 years. In our study 25 patients (32.89%) belonged to the age group of 21–30 years. Anti-MuSK antibodies were positive in 8 non-refractory MG patients (2.06%) and 36 refractory MG patients (47.36%). Mean HbA1C was found to be 8.6±2.33. The dose of administered prednisone decreased by a mean of 59.7% (p=3.3x10–8) to 94.6% (p=2.2x10–14) after the third cycle of rituximab treatment. Conclusion: The refractory MG patients are most commonly female with an early age of onset, anti-MuSK antibodies, and thymomas. Refractory MG patients have higher prevalence and poor control (HbA1C >8%) of diabetes mellitus and dyslipidemia probably due to increased steroid usage. Rituximab is very efficient in treatment of refractory MG with adverse effects being low. PMID:27790079

  6. Molecular detection of virulence factors among food and clinical Enterococcus faecalis strains in South Brazil

    Directory of Open Access Journals (Sweden)

    A.W. Medeiros

    2014-01-01

    Full Text Available The present report aimed to perform a molecular epidemiological survey by investigating the presence of virulence factors in E. faecalis isolated from different human clinical (n = 57 and food samples (n = 55 in Porto Alegre, Brazil, collected from 2006 to 2009. In addition, the ability to form biofilm in vitro on polystyrene and the β-haemolytic and gelatinase activities were determined. Clinical strains presented a higher prevalence of aggregation substance (agg, enterococcal surface protein (esp and cytolysin (cylA genes when compared with food isolates. The esp gene was found only in clinical strains. On the other hand, the gelatinase (gelE and adherence factor (ace genes had similar prevalence among the strains, showing the widespread occurrence of these virulence factors among food and clinical E. faecalis strains in South Brazil. More than three virulence factor genes were detected in 77.2% and 18.2% of clinical and food strains, respectively. Gelatinase and β-haemolysin activities were not associated with the presence of gelE and cylA genes. The ability to produce biofilm was detected in 100% of clinical and 94.6% of food isolates, and clinical strains were more able to form biofilm than the food isolates (Student's t-test, p < 0.01. Results from the statistical analysis showed significant associations between strong biofilm formation and ace (p = 0.015 and gelE (p = 0.007 genes in clinical strains. In conclusion, our data indicate that E. faecalis strains isolated from clinical and food samples possess distinctive patterns of virulence factors, with a larger number of genes that encode virulence factors detected in clinical strains.

  7. Clinical Profile and Outcome in Children of Dengue Hemorrhagic Fever in North India

    Directory of Open Access Journals (Sweden)

    Deepak Bhat

    2008-09-01

    Full Text Available Objective: The number of dengue fever (DF/dengue hemorrhagic fever (DHF cases reported in India has risen in recent years. This study was undertaken to evaluate clinical profile and outcome of children admitted with DHF/dengue shock syndrome (DSS, in the 2006 DHF epidemic in Ludhiana, Punjab. Methods: Eighty one children with dengue hemorrhagic fever were hospitalized in the Pediatric Department of Dayanand Medical College and Hospital, Ludhiana, India. All patients were diagnosed, managed and monitored according to a standard protocol. Findings: Children between 10-15 years were most commonly afflicted (59%. Infants were the least affected sub-group (3.7%. Ninety two percent of all children were of DHF and 8% cases presented in DSS. The common symptoms seen were fever (91%, vomiting (41%, poor intake (21%, abdominal pain (16% and significant bleeding (15%. Hepatomegaly was present in 60% of cases. 85% of cases had petechiae alone, 15% had evidence of significant bleeding manifestation. Gastrointestinal bleeding was the commonest observed bleeding. The complications seen were liver dysfunction (14.8%, coagulopathy (3.7%, renal dysfunction (3.7%, and acute respiratory distress syndrome (2.4% and disseminated intravascular coagulation (1.2%. Mortality in the study was 3.7%. Refractory shock and coagulopathy were seen in all cases with poor outcome. Conclusion: Increased awareness, better transport facilities and case management according to the WHO guidelines, is needed to further reduce mortality of DHF/DSS cases.

  8. Clinical Profile of Dengue Fever in Children: A Study from Southern Odisha, India.

    Science.gov (United States)

    Mishra, Shubhankar; Ramanathan, Ramya; Agarwalla, Sunil Kumar

    2016-01-01

    Background. In India, dengue epidemics are becoming more frequent (WHO, 2008). The majority of dengue viral infections are self-limiting, but complications may cause high morbidity and mortality. Objectives. To assess the clinical profile of the dengue infection in children less than 14 years of age and to evaluate the outcomes of dengue fever from September 2013 to August 2015 at the Pediatric Department of Maharaja Krishna Chandra Gajapati Medical College, the largest tertiary care hospital of southern Odisha. Results. A total of 97 cases were classified into 84 (86.59%) nonsevere and 13 (13.40%) severe dengue cases. The most common age of presentation was above 11 yrs. The mean age of admission was 8.7 yrs. The most common presenting symptom was fever seen in 100% and hepatomegaly (43.8%), the most common physical finding. Gastrointestinal bleeding was markedly seen in severe dengue (76.9%). Elevation in aspartate transaminase (SGOT) was found in 47.42% and thrombocytopenia in 27.5%. The correlation between hepatomegaly and elevated SGOT was significant (P value 0.0346). Case fatality rate (CFR) was 1.03%. The mean duration of hospitalisation was 3.8 days. Conclusion. In children, if symptoms like fever, pain, rashes, and vomiting are associated with hepatomegaly and elevated SGOT in context of low TPC, a strong possibility of dengue fever is present, especially in an epidemic setting. Early suspicion and effective management can reduce the severity. PMID:27213083

  9. Clinical and pharmacoeconomic profile of esomeprazole in acid-related diseases

    Directory of Open Access Journals (Sweden)

    Orietta Zaniolo

    2006-09-01

    Full Text Available Protonic pump inhibitors (PPIs are the most prescribed drugs for acute and maintenance therapy of gastroesophageal reflux disease, H. pylori-eradication (in association with antibacterial therapy, for ulcers prevention and cure and, recently, for prevention of NSAIDs-induced gastropathy. The high prevalence of these acid-related disorders induces a large consumption of PPIs; actually, they are the first drug class in terms of National Health Service pharmaceutical expenditure. This widespread and gradually increasing use enforces the need of a rational assessment of their impact on health care resources. This paper provides an updated profile of esomeprazole, the first PPI developed as a pure isomer, which property involves an advantageous metabolism, resulting in enhanced delivery to the proton pump compared with racemic omeprazole. Several studies showed that the success rate for healing reflux esophagitis is greater for esomeprazole than for omeprazole and some other PPIs. According to an Italian pharmacoeconomic model, esomeprazole therapy for erosive esophagitis is associated with higher benefits and lower costs as compared to omeprazole and pantoprazole. For long-term management of non-erosive gastroesophageal reflux disease, on-demand approach with esomeprazole shows clinical outcomes similar to daily treatment regimens, with substantial cost-saving. Furthermore, esomeprazole is the only PPI approved for 1-week triple therapy for both the eradication and the healing of H. pylori-associated duodenal ulcer, while the other PPIs registered the indication for H. pylori-eradication and, separately, a dosing scheme for ulcer healing (independently from etiology.

  10. A STUDY ON CLINICAL AND AETIOLOGICAL PROFILE OF HYPOKALAEMIC PARALYSIS IN A TERTIARY CARE HOSPITAL

    Directory of Open Access Journals (Sweden)

    Kekathi Vidyasagar

    2016-08-01

    Full Text Available BACKGROUND Hypokalaemic periodic paralysis is a rare disorder characterised by transient attacks of flaccid paralysis of varying intensity and frequency. Although mostly familial in aetiology, several sporadic cases with different causes have been reported. There are two groups of disorders predominantly that causes hypokalaemic paralysis. One group is due to transcellular shift of potassium and other is due to loss of potassium from body either through GI tract or through renal system. MATERIAL AND METHODS Here we report a study on the clinical and aetiological profile of 30 cases of hypokalaemic paralysis admitted in our institution between January 2014 to January 2016. RESULTS The aetiological workup of all the patients was done which revealed thyrotoxic periodic paralysis as the major cause in 12 of 30 patients. Three rare causes of hypokalaemia have been diagnosed which included Bartter’s syndrome, Mixed Connective tissue disorder, Sjogren’s syndrome. Vomiting and diarrhoea was seen in 12 of 30 patients. CONCLUSION Hypokalaemic periodic paralysis is a heterogenous group of disorder. A significant number of patients had thyroid disorders mostly in the form of thyrotoxicosis, non-renal and renal loss of potassium like diarrhoea and vomiting. Early recognition and prompt management of these conditions is essential to prevent residual deformity and further attacks in future.

  11. Characterization of rheumatoid arthritis subtypes using symptom profiles, clinical chemistry and metabolomics measurements.

    Directory of Open Access Journals (Sweden)

    Herman A van Wietmarschen

    Full Text Available OBJECTIVE: The aim is to characterize subgroups or phenotypes of rheumatoid arthritis (RA patients using a systems biology approach. The discovery of subtypes of rheumatoid arthritis patients is an essential research area for the improvement of response to therapy and the development of personalized medicine strategies. METHODS: In this study, 39 RA patients are phenotyped using clinical chemistry measurements, urine and plasma metabolomics analysis and symptom profiles. In addition, a Chinese medicine expert classified each RA patient as a Cold or Heat type according to Chinese medicine theory. Multivariate data analysis techniques are employed to detect and validate biochemical and symptom relationships with the classification. RESULTS: The questionnaire items 'Red joints', 'Swollen joints', 'Warm joints' suggest differences in the level of inflammation between the groups although c-reactive protein (CRP and rheumatoid factor (RHF levels were equal. Multivariate analysis of the urine metabolomics data revealed that the levels of 11 acylcarnitines were lower in the Cold RA than in the Heat RA patients, suggesting differences in muscle breakdown. Additionally, higher dehydroepiandrosterone sulfate (DHEAS levels in Heat patients compared to Cold patients were found suggesting that the Cold RA group has a more suppressed hypothalamic-pituitary-adrenal (HPA axis function. CONCLUSION: Significant and relevant biochemical differences are found between Cold and Heat RA patients. Differences in immune function, HPA axis involvement and muscle breakdown point towards opportunities to tailor disease management strategies to each of the subgroups RA patient.

  12. Cri-Du-Chat Syndrome: Clinical Profile and Chromosomal Microarray Analysis in Six Patients

    Directory of Open Access Journals (Sweden)

    Layla Damasceno Espirito Santo

    2016-01-01

    Full Text Available Cri-du-chat syndrome is a chromosomal disorder caused by a deletion of the short arm of chromosome 5. The disease severity, levels of intellectual and developmental delay, and patient prognosis have been related to the size and position of the deletion. Aiming to establish genotype-phenotype correlations, we applied array-CGH to evaluate six patients carrying cytogenetically detected deletions of the short arm of chromosome 5 who were followed at a genetics community service. The patients’ cytogenetic and clinical profiles were reevaluated. A database review was performed to predict additional genes and regulatory elements responsible for the characteristic phenotypic and behavioral traits of this disorder. Array-CGH analysis allowed for delineation of the terminal deletions, which ranged in size from approximately 11.2 Mb to 28.6 Mb, with breakpoints from 5p15.2 to 5p13. An additional dup(8(p23 (3.5 Mb, considered to be a benign copy number variation, was also observed in one patient. The correlation coefficient value (ρ=0.13 calculated indicated the presence of a weak relationship between developmental delay and deletion size. Genetic background, family history, epigenetic factors, quantitative trait locus polymorphisms, and environmental factors may also affect patient phenotype and must be taken into account in genotype-phenotype correlations.

  13. Socio Demographic and Clinical Profile of HIV Positive Antenatal Women Registered in PPTCT Centres, Surat, Gujarat

    Directory of Open Access Journals (Sweden)

    Grishma Chauhan, Anupam Verma, R.K.Bansal, Rachana Prasad

    2014-01-01

    Full Text Available Objective: The present study reports the socio demographic and clinical profile of 127 HIV positive antenatal women and their husbands. The findings of the study will be helpful for policy decision makers to address the issues of a specific vulnerable group. Materials and Methods: During Jan 2007 to Dec 2008, a total 282 ante-natal women were referred to 5 PPTCT centres for HIV testing and counseling. Of these 127 (45% antenatal women who came to collect their reports could be contacted for this study. The husbands of the 127 HIV positive antenatal women were contacted to collect their information. Result: Mean Age of HIV positive antenatal women was 25.5 ±3.8 years, more than 50% were in the age group of 20-25 years and 18.9% of HIV positive antenatal women were illiterate. HIV positivity rate in spouse was 80%. Two third women were diagnosed HIV positive in 2nd & 3rd trimester of pregnancy. Among the positive 60 (47.3% were primi gravidas, 27 (21.3% mothers were not tested for CD4 count. However 98 (77% mothers were registered in ART centre and 35% HIV positive an-tenatal women were on ART. Conclusion: HIV positive pregnant women were younger, primi and housewives. HIV positive antenatal women need to be followed rigorously to link them to ART services.

  14. Tubercular meningitis in children: Clinical, pathological, and radiological profile and factors associated with mortality

    Directory of Open Access Journals (Sweden)

    Anil V Israni

    2016-01-01

    Full Text Available Context: Childhood tuberculosis is a major public health problem in developing countries with tubercular meningitis being a serious complication with high mortality and morbidity. Aim: To study the clinicopathological as well as radiological profile of childhood tuberculous meningitis (TBM cases. Settings and Design: Prospective, observational study including children <14 years of age with TBM admitted in a tertiary care hospital from Western India. Subjects and Methods: TBM was diagnosed based on predefined criteria. Glassgow coma scale (GCS and intracranial pressure (ICP was recorded. Staging was done as per British Medical Council Staging System. Mantoux test, chest X-ray, cerebrospinal fluid (CSF examination, neuroimaging, and other investigations were done to confirm TB. Statistical Analysis Used: STATA software (version 9.0 was used for data analysis. Various risk factors were determined using Chi-square tests, and a P< 0.05 was considered significant. Results: Forty-seven children were included, of which 11 (24.3% died. Fever was the most common presenting symptom, and meningismus was the most common sign. Twenty-nine (62% children presented with Stage III disease. Stage III disease, low GCS, and raised ICP were predictors of mortality. Findings on neuroimaging or CSF examination did not predict mortality. Conclusions: Childhood TBM presents with nonspecific clinical features. Stage III disease, low GCS, lack of Bacillus Calmette–Gu͹rin vaccination at birth and raised ICP seem to the most important adverse prognostic factors.

  15. Profile of pregnancy in adolescence and related clinical-obstetric occurrences

    Directory of Open Access Journals (Sweden)

    Maria Veraci Oliveira Queiroz

    2014-09-01

    Full Text Available The objective was to characterize the profile of adolescence pregnancy and its clinical and obstetric events. Descriptive, cross-sectional study, with quantitative approach, developed in a tertiary hospital in Fortaleza, CE, Brazil, with one hundred adolescent mothers, through interviews and registers from the medical records, from February to May, 2011. Data were analyzed by Statistical Package for the Social Science software, version 17.0. The majority lived with a partner who earned up to one minimum wage, had low education and unpaid occupational activity. Most of them also reported early sexual activity, and were primiparas. All of them had complete prenatal care, with an average number of 5.91 consultations. The percentage of uncomplicated births of newborns was 48.9%, being prematurity the most frequent (56.3%. It is necessary to have more encouragement to young mothers attending postnatal consultation and family planning, and to have access and learning contraceptive matters, making prevention to early pregnancy more effective.

  16. Dyslipidemia and cardiovascular disease risk profiles of patients attending an HIV treatment clinic in Harare, Zimbabwe

    Directory of Open Access Journals (Sweden)

    Zhou DT

    2015-05-01

    Full Text Available Danai Tavonga Zhou,1,2 Vitaris Kodogo,1 Kudzai Fortunate Vongai Chokuona,1 Exnevia Gomo,1 Olav Oektedalen,3 Babill Stray-Pedersen21Department of Medical Laboratory Sciences, College of Health Sciences, University of Zimbabwe, Avondale, Zimbabwe; 2Institute of Clinical Medicine, University in Oslo, Oslo University Hospital, Oslo, Norway; 3Department of Infectious Diseases, Oslo University Hospital, Oslo, NorwayAbstract: The chronic inflammation induced by human immunodeficiency virus (HIV contributes to increased risk of coronary heart disease (CHD in HIV-infected individuals. HIV-infected patients generally benefit from being treated with antiretroviral drugs, but some antiretroviral agents have side effects, such as dyslipidemia and hyperglycemia. There is general consensus that antiretroviral drugs induce a long-term risk of CHD, although the levels of that risk are somewhat controversial. The intention of this cross-sectional study was to describe the lipid profile and the long-term risk of CHD among HIV-positive outpatients at an HIV treatment clinic in Harare, Zimbabwe. Two hundred and fifteen patients were investigated (females n=165, mean age 39.8 years; males n=50; mean age 42.0 years. Thirty of the individuals were antiretroviral-naïve and 185 had been on antiretroviral therapy (ART for a mean 3.9±3.4 years. All participants had average lipid and glucose values within normal ranges, but there was a small difference between the ART and ART- for total cholesterol (TC and high-density lipoprotein (HDL.Those on a combination of D4T or ZDV/NVP/3TC and PI-based ART were on average oldest and had the highest TC levels. Framingham risk showed 1.4% prevalence of high CHD risk within the next ten years. After univariate analysis age, sex, TC/HDL ratio, HDL, economic earnings and systolic BP were associated with medium to high risk of CHD. After multivariate regression analysis and adjusting for age or sex only age, sex and economic earnings

  17. Effects of ray profile modeling on resolution recovery in clinical CT

    Energy Technology Data Exchange (ETDEWEB)

    Hofmann, Christian [Institute of Medical Physics, Friedrich–Alexander University (FAU), Erlangen, Bavaria 91052 (Germany); Knaup, Michael [Medical Physics in Radiology, German Cancer Research Center (DKFZ), Heidelberg 69120 (Germany); Kachelrieß, Marc, E-mail: marc.kachelriess@dkfz-heidelberg.de [Medical Physics in Radiology, German Cancer Research Center (DKFZ), Heidelberg 69120, Germany and Institute of Medical Physics, Friedrich–Alexander University (FAU), Erlangen, Bavaria 91052 (Germany)

    2014-02-15

    Purpose: Iterative image reconstruction gains more and more interest in clinical routine, as it promises to reduce image noise (and thereby patient dose), to reduce artifacts, or to improve spatial resolution. However, among vendors and researchers, there is no consensus of how to best achieve these goals. The authors are focusing on the aspect of geometric ray profile modeling, which is realized by some algorithms, while others model the ray as a straight line. The authors incorporate ray-modeling (RM) in nonregularized iterative reconstruction. That means, instead of using one simple single needle beam to represent the x-ray, the authors evaluate the double integral of attenuation path length over the finite source distribution and the finite detector element size in the numerical forward projection. Our investigations aim at analyzing the resolution recovery (RR) effects of RM. Resolution recovery means that frequencies can be recovered beyond the resolution limit of the imaging system. In order to evaluate, whether clinical CT images can benefit from modeling the geometrical properties of each x-ray, the authors performed a 2D simulation study of a clinical CT fan-beam geometry that includes the precise modeling of these geometrical properties. Methods: All simulations and reconstructions are performed in native fan-beam geometry. A water phantom with resolution bar patterns and a Forbild thorax phantom with circular resolution patterns representing calcifications in the heart region are simulated. An FBP reconstruction with a Ram–Lak kernel is used as a reference reconstruction. The FBP is compared to iterative reconstruction techniques with and without RM: An ordered subsets convex (OSC) algorithm without any RM (OSC), an OSC where the forward projection is modeled concerning the finite focal spot and detector size (OSC-RM) and an OSC with RM and with a matched forward and backprojection pair (OSC-T-RM, T for transpose). In all cases, noise was matched to

  18. Molecular profiling reveals diversity of stress signal transduction cascades in highly penetrant Alzheimer's disease human skin fibroblasts.

    Directory of Open Access Journals (Sweden)

    Graziella Mendonsa

    Full Text Available The serious and growing impact of the neurodegenerative disorder Alzheimer's disease (AD as an individual and societal burden raises a number of key questions: Can a blanket test for Alzheimer's disease be devised forecasting long-term risk for acquiring this disorder? Can a unified therapy be devised to forestall the development of AD as well as improve the lot of present sufferers? Inflammatory and oxidative stresses are associated with enhanced risk for AD. Can an AD molecular signature be identified in signaling pathways for communication within and among cells during inflammatory and oxidative stress, suggesting possible biomarkers and therapeutic avenues? We postulated a unique molecular signature of dysfunctional activity profiles in AD-relevant signaling pathways in peripheral tissues, based on a gain of function in G-protein-coupled bradykinin B2 receptor (BKB2R inflammatory stress signaling in skin fibroblasts from AD patients that results in tau protein Ser hyperphosphorylation. Such a signaling profile, routed through both phosphorylation and proteolytic cascades activated by inflammatory and oxidative stresses in highly penetrant familial monogenic forms of AD, could be informative for pathogenesis of the complex multigenic sporadic form of AD. Comparing stimulus-specific cascades of signal transduction revealed a striking diversity of molecular signaling profiles in AD human skin fibroblasts that express endogenous levels of mutant presenilins PS-1 or PS-2 or the Trisomy 21 proteome. AD fibroblasts bearing the PS-1 M146L mutation associated with highly aggressive AD displayed persistent BKB2R signaling plus decreased ERK activation by BK, correctible by gamma-secretase inhibitor Compound E. Lack of these effects in the homologous PS-2 mutant cells indicates specificity of presenilin gamma-secretase catalytic components in BK signaling biology directed toward MAPK activation. Oxidative stress revealed a JNK-dependent survival

  19. Large-scale cellular-resolution gene profiling in human neocortex reveals species-specific molecular signatures

    Science.gov (United States)

    Zeng, Hongkui; Shen, Elaine H.; Hohmann, John G.; Oh, Wook Seung; Bernard, Amy; Royall, Joshua J.; Glattfelder, Katie J.; Sunkin, Susan M.; Morris, John A.; Guillozet-Bongaarts, Angela L.; Smith, Kimberly A.; Ebbert, Amanda J.; Swanson, Beryl; Kuan, Leonard; Page, Damon T.; Overly, Caroline C.; Lein, Ed S.; Hawrylycz, Michael J.; Hof, Patrick R.; Hyde, Thomas M.; Kleinman, Joel E.; Jones, Allan R.

    2012-01-01

    Summary Although there have been major advances in elucidating the functional biology of the human brain, relatively little is known of its cellular and molecular organization. Here we report a large-scale characterization of the expression of ~1,000 genes important for neural functions, by in situ hybridization with cellular resolution in visual and temporal cortices of adult human brains. These data reveal diverse gene expression patterns and remarkable conservation of each individual gene’s expression among individuals (95%), cortical areas (84%), and between human and mouse (79%). A small but substantial number of genes (21%) exhibited species-differential expression. Distinct molecular signatures, comprised of genes both common between species and unique to each, were identified for each major cortical cell type. The data suggest that gene expression profile changes may contribute to differential cortical function across species, in particular, a shift from corticosubcortical to more predominant corticocortical communications in the human brain. PMID:22500809

  20. Molecular Characterization of Staphylococcus aureus Isolated from Meat and Their Antibiotic Resistance Profiles

    Directory of Open Access Journals (Sweden)

    Ziad W Jaradat

    2014-01-01

    Full Text Available The aims of this study were to characterize S. aureus isolates from different meat sources in Jordan and study their genetic relationship using PCR-RFLP in addition to their antibiotic resistance profiles. Thirty S. aureus isolates were identified and confirmed by PCR techniques. The isolates from goat and camel meats were sensitive to the majority of the tested antibiotics. Plasmid profiling revealed that 26 isolates contained at least one plasmid with no correlation between the number of plasmids and the resistance profiles. PCR-RFLP of the coagulase gene (coa classified the isolates to several clusters upon digestion with Alu I or Cfo I restriction enzymes. This study concluded that the 30 S. aureus isolates were genetically diverse and comprised heterogeneous population with 7 genotypes at both 33.1 and 51.2 similarity levels.

  1. Automated Broad-Range Molecular Detection of Bacteria in Clinical Samples.

    Science.gov (United States)

    Budding, Andries E; Hoogewerf, Martine; Vandenbroucke-Grauls, Christina M J E; Savelkoul, Paul H M

    2016-04-01

    Molecular detection methods, such as quantitative PCR (qPCR), have found their way into clinical microbiology laboratories for the detection of an array of pathogens. Most routinely used methods, however, are directed at specific species. Thus, anything that is not explicitly searched for will be missed. This greatly limits the flexibility and universal application of these techniques. We investigated the application of a rapid universal bacterial molecular identification method, IS-pro, to routine patient samples received in a clinical microbiology laboratory. IS-pro is a eubacterial technique based on the detection and categorization of 16S-23S rRNA gene interspace regions with lengths that are specific for each microbial species. As this is an open technique, clinicians do not need to decide in advance what to look for. We compared routine culture to IS-pro using 66 samples sent in for routine bacterial diagnostic testing. The samples were obtained from patients with infections in normally sterile sites (without a resident microbiota). The results were identical in 20 (30%) samples, IS-pro detected more bacterial species than culture in 31 (47%) samples, and five of the 10 culture-negative samples were positive with IS-pro. The case histories of the five patients from whom these culture-negative/IS-pro-positive samples were obtained suggest that the IS-pro findings are highly clinically relevant. Our findings indicate that an open molecular approach, such as IS-pro, may have a high added value for clinical practice. PMID:26763956

  2. Molecular and clinical characterization of patients with overlapping 10p deletions.

    Science.gov (United States)

    Lindstrand, Anna; Malmgren, Helena; Verri, Annapia; Benetti, Elisa; Eriksson, Maud; Nordgren, Ann; Anderlid, Britt-Marie; Golovleva, Irina; Schoumans, Jacqueline; Blennow, Elisabeth

    2010-05-01

    Chromosome 10p terminal deletions have been associated with DiGeorge phenotype, and within the same genomic region haploinsufficiency of GATA3 causes the HDR syndrome (hypoparathyroidism, sensorineural deafness, renal dysplasia). We have performed detailed molecular analysis of four patients with partial overlapping 10p deletions by using FISH-mapping, array-CGH, and custom-designed high-resolution oligonucleotide array. All four patients had mental retardation and speech impairment and three of them showed variable signs of HDR syndrome. In addition, two patients had autistic behaviors and had similar dysmorphic features giving them a striking physical resemblance. A review of the literature identified 10 previously published cases with similar 10p deletions and reliable molecular or molecular cytogenetic mapping data. The combined information of present and previous cases suggests that partial deletions of 10p14-p15 represent a syndrome with a distinct and more severe phenotype than previously assumed. The main characteristics include severe mental retardation, language impairment, autistic behavior, and characteristic clinical features. A critical region involved in mental retardation and speech impairment is defined within 1.6 Mb in 10p15.3. In addition, deletion of 4.3 Mb within 10p14 is associated with autism and characteristic clinical findings. PMID:20425828

  3. Update on the clinical use of the low-molecular-weight heparin, parnaparin

    Directory of Open Access Journals (Sweden)

    Giuseppe Camporese

    2009-09-01

    Full Text Available Giuseppe Camporese1, Enrico Bernardi2, Franco Noventa31Unit of Angiology and 3Department of Clinical and Experimental Medicine, Clinical Epidemiology Group, University Hospital of Padua, Italy; 2Department of Emergency and Accident Medicine, Hospital of Conegliano Veneto, ItalyAbstract: Parnaparin is a low-molecular-weight heparin that has widely shown its efficacy and safety in prevention of venous thromboembolism, in the treatment of chronic venous disorders, and in the treatment of venous and arterial (stable and unstable angina, acute ST-segment elevation myocardial infarction thrombosis. Parnaparin at the respective dosages of 3200, 4250, 6400, or 12800 IUaXa for a period ranging from 3 to 5 days to 6 months, is usually administered subcutaneously by means of once-daily regimen and is better tolerated than unfractionated heparin at the injection site. In the variety of commercially available low-molecular-weight heparins, parnaparin represents a useful therapeutic option, even though little evidence is available comparing the superiority or the equivalent efficacy and safety of parnaparin to that of the unfractionated heparin or placebo. This review summarizes the available literature on the use of parnaparin in different settings of cardiovascular diseases, including papers published during the past year and ongoing studies.Keywords: low-molecular-weight heparin, heparin, parnaparin, acute coronary syndromes, venous thromboembolism

  4. Molecular typing of clinical isolates of Cryptococcus neoformans/Cryptococcus gattii species complex from Northeast Mexico.

    Science.gov (United States)

    González, Gloria M; Casillas-Vega, Néstor; Garza-González, Elvira; Hernández-Bello, Romel; Rivera, Gildardo; Rodríguez, Jesús Ancer; Bocanegra-Garcia, Virgilio

    2016-01-01

    Cryptococcosis is caused by members of the Cryptococcus neoformans/Cryptococcus gattii species complex. Based on molecular identification, these two species have been further differentiated into molecular types. The aim of this work was to characterize clinical cryptococcal isolates recovered from six hospitals in Northeast Mexico from 1995 to 2011. One hundred and sixty-six isolates, which were characterized by biochemical tests and in vitro susceptibility to amphotericin B, fluconazole, and voriconazole, and M13 PCR fingerprinting, were included in this study. Utilizing phenotypic tests, 153 isolates (92.16 %) were identified as C. neoformans and 13 (7.83 %) as C. gattii. All isolates were susceptible to all antifungals tested. Employing M13 PCR fingerprinting, eight molecular types were detected. VNI was the most common genotype (124 cases; 74.6 %), followed by VNII (15 cases; 9 %), VNIII (8 cases; 4.8 %), VNIV (6 cases; 3.6 %), VGI (6 cases; 3.6 %), VGII (3 cases; 1.8 %), and VGIII and VGIV (2 cases, 1.2 % each). We confirm the presence of C. gattii in clinical isolates in Northeast Mexico, and a high clonal diversity in the studied strains of C. neoformans/C. gattii species complex.

  5. Juvenile neuronal ceroid-lipofuscinosis: clinical and molecular investigation in a large family in Brazil

    Directory of Open Access Journals (Sweden)

    Eugênia Ribeiro Valadares

    2011-02-01

    Full Text Available OBJECTIVE: Juvenile Neuronal Ceroid-Lipofuscinosis (JNCL, CLN 3, Batten Disease (OMIM #204200 belongs to the most common group of neurodegenerative disorders of childhood. We report the clinical data and molecular analysis of a large Brazilian family. METHOD: Family composed of two consanguineous couples and thirty-two children. Clinical data of ten JNCL patients and molecular analyses on 13 participants were obtained. RESULTS: The large 1.02 kb deletion was detected. The most severe phenotype, with autistic behavior, tics and parkinsonism was seen in a 12-year-old female and a milder phenotype in a 14-year-old male. Nyctalopia was the first symptom in one deceased child. The visual loss of six patients has been first observed in the school and not at home. CONCLUSION: The report highlights the phenotypical intrafamily variation in 10 affected children of this family. The molecular investigation of this large family in our metabolic center turned possible the diagnosis, right approach and genetic counseling.

  6. Clinical profile of patients with myasthenia gravis followed at the University Hospital, Federal University of Minas Gerais

    Directory of Open Access Journals (Sweden)

    Aline Mansueto Mourão

    2015-04-01

    Full Text Available Summary Objective: to determine the clinical profile of patients with myasthenia gravis (MG; followed at the Neuromuscular Diseases Clinic of the University Hospital, Federal University of Minas Gerais, Brazil, and to compare it with other Brazilian case series. Methods: sociodemographic and clinical data were collected from patients, and a systematic literature review performed, focusing on national studies on the clinical profile of MG patients. Results: sixty nine patients were enrolled in the study. Fifty five (91% subjects were female and the mean age (SD was 37.6 (±11.4 years. The mean disease duration was 14.1 years. Regarding treatment, prednisone was the most used strategy (64%, followed by the use of azathioprine (43%. There was no difference between thymectomized (42 and non-thymectomized (27 patients regarding disease severity and medication use. Conclusion: clinical and socio-demographic features of this MG sample from a University-based clinic resemble those reported in other Brazilian series and in the international literature.

  7. CLINICAL AND ETIOLOGICAL PROFILE OF PATIENTS WITH LUNG ABSCESS AT A TERTIARY CARE CENTRE

    Directory of Open Access Journals (Sweden)

    Manoj Kumar

    2015-10-01

    Full Text Available BACKGROUND: Lung abscess is a type of liquefactive necrosis of the lung tissue and formation of cavities (more than 2 cm containing necrotic debris or fluid caused by microbial infection. This pus - filled cavity is often caused by aspiration, which may occur during altered consciousness. OBJECTIVE: To study the clinical and etiological profile of lung abscess in patients admitted at a tertiary care centre. MATERIAL AND METHODS : A prospective study was condu cted on 142 cases with age more than 15 years, who were the suspected cases of lung abscess and the cases with evidence of lung abscess on the X - ray, CT scan presented to the OPD/ IPD clinic, Department of Pulmonary Medicine, Rohilkhand Medical College and Hospital (RMCH, Bareilly from January 2013 to December 2014 were included in the study. RESULTS: out of 142 patients enrolled in the study, 47(33.09% belonged to age group of ›60 years followed by 42(29.57% belong to 41 - 60 years of age. 116(81.6% wer e male and 26(18.3% were female. The most frequent symptom was cough (92.95%, followed by expectoration (91.54%, fever (87.32% and hemoptysis (41.5%. CONCLUSION: In our study conducted, data collection shows that lung abscess was more seen in the elderly and male patients 116( 81.6% as compared to female patients 26(18.3%. Majority of the patients had a risk factor of smoking, dental diseases, altered sensorium, comatosed patients, alcohol, diabetes, on steroid therapy and immunocompromised immune status. The following were the major symptoms in our patients : - Cough (92.95%, expectoration (91.54% , Fever(87.32%, Foul smell (66.90% , Chest pain (58.45% , Hemoptysis (41.5%, Impaired consciousness (29.57%. In our study locus of lesion was more pro minently on right side i.e. 101 patients ( 71.12% as compared to 36 ( 25.35%,while lung abscess was seen bilateral in 5 patients ( 3.5%. Primary lung abscess is a common presentation amongst the patients with the periodontal diseases, seizure

  8. CLINICAL, BIOCHEMICAL AND HISTOPATHOLOGICAL PROFILE OF ADULT NEPHROTIC SYNDROME PATIENTS IN A TERTIARY CARE HOSPITAL

    Directory of Open Access Journals (Sweden)

    Krishnamoorthy

    2015-09-01

    Full Text Available BACKGROUND: The nephrotic syndrome is recognized as an independent entity of renal disease for over half a century . 1 Causes of nephrotic syndrome varies with age, time period, geographical location and race. In children, minimal change nephrotic syndrome is the commonest 2 ; however, membranous nephropathy is most frequent in adults . 3 As it commonly affects the younger age group and is associated with high morbidity and mortality, there is a need to understand and diagnose the disease at an early stage. Hence, this study has been done to identify the clinical presentation, biochemical parameters and histopathology associated with nephrotic syndrome in adults and its subtypes. OBJECTIVE: To study the clinical, biochemical and histopathological profile of patients with Adult Nephrotic Syndrome admitted in our tertiary care hospital. METHODS: Prospective study of 100 patients with Adult Nephrotic Syndrome admitt ed in our tertiary care hospital were screened with facial puffiness and pedal edema. They were tested for urine proteinuria, urine protein creatinine ratio or 24 hour urine protein estimation. Later renal biopsy was done for all patients to stratify the subtypes. RESULTS: In this study, males were predominantly affected. Most common presenting complaints were facial puffiness and pedal edema. Systolic BP was increased in 96% of patients and diastolic BP was elevated in 50% of patients. Serum LDL and TGL were elevated in nephrotic syndrome. In young patients less than 40 years Focal Segmental Glomerulosclerosis (FSGS is the commonest type, then Membrano Proliferative Glomerulo Nephritis (MPGN and Minimal Change Disease (MCD. In individuals more than 40 years, membranous nephropathy was predominantly seen followed by FSGS. CONCLUSION: There is a changing trend in primary nephrotic syndrome and FSGS was found to be the commonest subtype. Male preponderance was noticed and also FSGS was found to be more common in younger adults. Most

  9. Demographic, epidemiologic and clinical profile of snake bite cases, presented to Emergency Medicine department, Ahmedabad, Gujarat

    Directory of Open Access Journals (Sweden)

    Bhavesh Jarwani

    2013-01-01

    Full Text Available Aim: Snake bite is a common medical emergency faced mainly by the rural populations in tropical and subtropical countries with heavy rainfall and humid climate. Although India is a single largest contributor of snake bite cases, reporting is very poor. There is hardly any publication of the same from Gujarat state that is developing at a good pace. Hence, we aimed to study the snake bite cases with particular attention to demography, epidemiology, and clinical profile. Settings and Design: The present descriptive, observational study was carried out at the Emergency Medicine Department of a tertiary care center in Ahmedabad, Gujarat. This department is one if the firsts to get recognized by the Medical Council of India. Materials and Methods: This is a cross-sectional single-center study. Cases were entered into the prescribed form, and detailed information regarding demographic, epidemiologic, and clinical parameters was entered. Statistical Method: Data were analyzed using Epi2000. Means and frequencies for each variable were calculated. Results: Majority (67.4% of the snake bite victims were in the age group between 15 and 45 years. Majority were male victims (74.2%. 71% victims of snake bite lived in rural areas. Farmers and laborers were the main victims. 61.2% incidents took place at night time or early morning (before 6 a.m.. 64% patients had bite mark on the lower limb. 40% victims had seen the snake. Eight patients had snake bite, but were asymptomatic. 52% had neuroparalytic manifestation, 34% were asymptomatic, and 9.6% had hemorrhagic manifestation. 14% cases received treatment within 1 h of the bite and 64.84% within 1-6 h after the bite. First aid given was in the form of application of tourniquet (16.2%, local application of lime, chillies, herbal medicine, etc., (1%. 2.20% cases were sensitive to anti-snake venom. Only three patients died. Conclusion: In this region (Gujarat, neuroparalytic manifestation of snake bite is more

  10. Clinical profile of psychogenic non-epileptic seizures in adults: A study of 63 cases

    Directory of Open Access Journals (Sweden)

    Yogesh Patidar

    2013-01-01

    Full Text Available Aims: To evaluate clinical profile and short-term outcome of psychogenic non-epileptic seizures (PNES in Indian adult population. Setting and Design: A prospective observational study, conducted at tertiary teaching institute at New Delhi. Materials and Methods: Sixty-three patients with confirmed PNES were enrolled. The diagnosis was based on witnessing the event during video-electroencephalography (Video-EEG monitoring. A detailed clinical evaluation was done including evaluation for coexistent anxiety or depressive disorders. Patients were divided into two groups on the basis of excessive or paucity of movements during PNES attacks. Patients were followed-up to 12 months for their PNES frequency. Statistical Analysis: Means and standard deviations were calculated for continuous variables. Chi-square and Students t-test were used to compare categorical and continuous variables respectively. Results: The mean age at onset of PNES was 25.44 years; with F:M ratio of 9.5:1. Coexistent epilepsy was present in 13 (20.63% cases. Twenty-two patients (44% with only PNES ( n = 50 had received antiepileptic drugs. Out of 63 patients of PNES 24 (38.1% had predominant motor phenomenon, whereas 39 (61.9% had limp attacks. The common features observed were pre-ictal headache, ictal eye closure, jaw clenching, resistant behavior, ictal weeping, ictal vocalization, and unresponsiveness during episodes. Comorbid anxiety and depressive disorders was seen in 62.3% and 90.16% patients, respectively. Short-term (6-12 months outcome of 45 patients was good (seizure freedom in 46.66% and >50% improvement in 24.44% cases. Conclusion: PNES is common, but frequently misdiagnosed and treated as epileptic seizures. A high index of suspicion is required for an early diagnosis. Proper disclosure of diagnosis and management of the psychiatric comorbidities can improve their outcome. Limitation: Limited sample size and change in seizures frequency as the only parameter for

  11. MicroRNA Expression Profiling Identifies Molecular Diagnostic Signatures for Anaplastic Large Cell Lymphoma

    DEFF Research Database (Denmark)

    Liu, Cuiling; Iqbal, Javeed; Teruya-Feldstein, Julie;

    2013-01-01

    Anaplastic large-cell lymphomas (ALCLs) encompass at least 2 systemic diseases distinguished by the presence or absence of anaplastic lymphoma kinase (ALK) expression. We performed genome-wide microRNA (miRNA) profiling on 33 ALK-positive (ALK[+]) ALCLs, 25 ALK-negative (ALK[-]) ALCLs, 9 angioimm...

  12. Line profiles of molecular ions toward the pre-stellar core LDN 1544

    CERN Document Server

    Van der Tak, F F S; Ceccarelli, C

    2005-01-01

    Velocity profiles of ground state lines of H2D+, HC18O+ and N2H+, observed previously with the CSO and IRAM 30m telescopes, are modeled with a Monte Carlo radiative transfer program to study the temperature, density and velocity structure of the pre-stellar core LDN 1544. The H2D+ line is double-peaked like that of the other ions, but previous models that fit the HC18O+ and N2H+ profiles are found not to fit the H2D+ data. Matching the H2D+ observations requires at least three modifications to the model at small radii: (1) the density profile must continue to rise inward and not flatten off toward the center; (2) the gas temperature must be nearly constant and not drop inwards significantly; (3) the infall velocity must increase inward, in a fashion intermediate between `quasi-static' (ambipolar diffusion) and `fully dynamic' (Larson-Penston) collapse. The C18O emission indicates a chemical age of <~0.1 Myr. The effects of a flattened structure and rotation on the line profiles are shown to be unimportant,...

  13. Immunohistochemical and molecular profiling of histologically defined apocrine carcinomas of the breast.

    Science.gov (United States)

    Vranic, Semir; Marchiò, Caterina; Castellano, Isabella; Botta, Cristina; Scalzo, Maria Stella; Bender, Ryan P; Payan-Gomez, Cesar; di Cantogno, Ludovica Verdun; Gugliotta, Patrizia; Tondat, Fabrizio; di Celle, Paola Francia; Mariani, Sara; Gatalica, Zoran; Sapino, Anna

    2015-09-01

    Despite the marked improvement in the understanding of molecular mechanisms and classification of apocrine carcinoma, little is known about its specific molecular genetic alterations and potentially targetable biomarkers. In this study, we explored immunohistochemical and molecular genetic characteristics of 37 invasive apocrine carcinomas using immunohistochemistry (IHC), fluorescent in situ hybridization (FISH), multiplex ligation-dependent probe amplification (MLPA), and next-generation sequencing (NGS) assays. IHC revealed frequent E-cadherin expression (89%), moderate (16%) proliferation activity [Ki-67, phosphohistone H3], infrequent (~10%) expression of basal cell markers [CK5/6, CK14, p63, caveolin-1], loss of PTEN (83%), and overexpression of HER2 (32%), EGFR (41%), cyclin D1 (50%), and MUC-1 (88%). MLPA assay revealed gene copy gains of MYC, CCND1, ZNF703, CDH1, and TRAF4 in 50% or greater of the apocrine carcinomas, whereas gene copy losses frequently affected BRCA2 (75%), ADAM9 (54%), and BRCA1 (46%). HER2 gain, detected by MLPA in 38% of the cases, was in excellent concordance with HER2 results obtained by IHC/FISH (κ = 0.915, P carcinomas exhibit complex molecular genetic alterations that are consistent with the "luminal-complex" phenotype. Some of the identified molecular targets are promising biomarkers; however, functional studies are needed to prove these observations.

  14. Child behaviour checklist emotional dysregulation profiles in youth with disruptive behaviour disorders: clinical correlates and treatment implications.

    Science.gov (United States)

    Masi, Gabriele; Muratori, Pietro; Manfredi, Azzurra; Pisano, Simone; Milone, Annarita

    2015-01-30

    Two Child Behaviour Checklist (CBCL) profiles were correlated to poor self-regulation, Deficient Emotional Self-Regulation (DESR) (elevation between 1 and 2 Standard Deviations (SD) in Anxiety/Depression, Aggression, Attention subscales), and Dysregulation Profile (DP) (elevation of 2 Standard Deviations or more). We explored youths with Oppositional Defiant Disorder (ODD) and Conduct Disorder (CD) whether these profiles are associated with specific clinical features. The sample included 57 patients with DESR profile and 41 with DP profile, ages 9 to 15 years, all assigned to a non-pharmacological Multimodal Treatment Program. No differences resulted between groups in demographic features, diagnosis ratio, and comorbidities with Attention Deficit Hyperactivity Disorder (ADHD), Bipolar Disorder (BD), and Anxiety Disorder. The DP group was associated with higher scores in Withdrawn, Social Problem, Thought, Rule Breaking, and Somatic CBCL subscales, and higher scores in Narcissism and Impulsivity (but not Callous-Unemotional (CU)), according to the Antisocial Process Screening Device (APSD). After treatment, patients with DESR improved their personality traits (Narcissistic and Callous-Unemotional, but not Impulsivity), while changes in CBCL scales were modest. Patients with DP improved scales of Attention, Aggression, Anxiety-Depression, Rule Breaking, Withdrawal, Social Problem and Thought, while personality features did not change. These results suggest diagnostic implications of CBCL profiles, and indications for targeted treatment strategies. PMID:25480545

  15. Bacteriological and clinical profile of Community acquired pneumonia in hospitalized patients

    Directory of Open Access Journals (Sweden)

    Shah Bashir

    2010-01-01

    Full Text Available The aim of our study was to obtain comprehensive insight into the bacteriological and clinical profile of community-acquired pneumonia requiring hospitalization. The patient population consisted of 100 patients admitted with the diagnosis of community-acquired pneumonia (CAP, as defined by British Thoracic society, from December 1998 to Dec 2000, at the Sher- i-Kashmir institute of Medical Sciences Soura, Srinagar, India. Gram negative organisms were the commonest cause (19/29, followed by gram positive (10/29. In 71 cases no etiological cause was obtained. Pseudomonas aeruginosa was the commonest pathogen (10/29, followed by Staphylococcus aureus (7/29, Escherichia coli (6/29, Klebsiella spp. (3/29, Streptococcus pyogenes (1/29, Streptococcus pneumoniae (1/29 and Acinetobacter spp. (1/29. Sputum was the most common etiological source of organism isolation (26 followed by blood (6, pleural fluid (3, and pus culture (1. Maximum number of patients presented with cough (99%, fever (95%, tachycardia (92%, pleuritic chest pain (75%, sputum production (65% and leucocytosis (43%. The commonest predisposing factors were smoking (65%, COPD (57%, structural lung disease (21%, diabetes mellitus (13%, and decreased level of consciousness following seizure (eight per cent and chronic alcoholism (one per cent. Fourteen patients, of whom, nine were males and five females, died. Staphylococcus aureus was the causative organism in four, Pseudomonas in two, Klebsiella in one, and no organism was isolated in seven cases. The factors predicting mortality at admission were - age over 62 years, history of COPD or smoking, hypotension, altered sensorium, respiratory failure, leucocytosis, and s0 taphylococcus pneumonia and undetermined etiology. The overall rate of identification of microbial etiology of community-acquired pneumonia was 29%, which is very low, and if serological tests for legionella, mycoplasma and viruses are performed the diagnostic yield would

  16. Etiology and clinical profile of patients with Cushing's syndrome: A single center experience

    Science.gov (United States)

    Ammini, Ariacherry C.; Tandon, Nikhil; Gupta, Nandita; Bhalla, Ashu Seith; Devasenaspathy, Kandaswamy; Kumar, Guresh; Sahoo, Jaiprakash P.; Chittawar, Sachin; Philip, Jim; Baruah, Manas P.; Dwarakanath, C. S.; Tripathi, Sudhir

    2014-01-01

    Background: There is little published literature on the profile of patients with Cushing's syndrome (CS) from India. The aim of this study was to compile data of CS patients treated at this hospital. Materials and Methods: Patients referred to the endocrine services of this hospital for diagnosis/treatment of CS from January 1985 to July 2012 were the subjects for this study. All patients had detailed medical history, physical examination and biochemical and hormonal assays (which changed with availability of tests and changing views). Assays for plasma adrenocorticotropic hormone (ACTH) (late 90s), salivary cortisol estimation, IJV sampling for ACTH and corticotrophin releasing hormone stimulation tests were added on later. Imaging included computed tomography (CT), magnetic resonance imaging (since the late 80's) and 68Ga DOTA-TOC/FDG PET-CT (2008). Results: Three hundred sixty-four patients (250 females, 114 males, age 6 months to 65 years, mean 28 years + 12 years) were diagnosed to have CS during this period. Two hundred and ninety-three patients (80.5%) were ACTH dependent (CD 215, ectopic ACTH syndrome 22, occult ACTH source 56) while 71 (19.5%) were ACTH independent (adrenal carcinoma 36, adenoma 30, primary pigmented nodular adrenal disease 4, AIMAH 1). Pituitary macro adenoma was seen in 14% of the CD cases. The most common presenting complaints were hypertension and diabetes mellitus. A total of 63% patients complained of weight gain while 15% had lost weight. Myopathy, infections, skeletal fractures and psychiatric problems were the other common observations in our patients. Conclusion: The clinical spectrum was broad. CD was the most common cause for CS. PMID:24701438

  17. A study on the clinical profile of ulcers and membranous lesions of oral cavity and oropharynx

    Directory of Open Access Journals (Sweden)

    T. D. Thimmappa

    2014-02-01

    Full Text Available Background: An ulcer is a discontinuity of an epithelial surface. Many a times, patients with oral ulcers are treated sympathetically without even coming to a definitive conclusion of their problem. Oral ulcers are common diseases for which patient seeks medical advice. Till date the clinical profile to diagnose the oral ulcers, membranous lesions of oral cavity and oropharynx is not well established. Hence, the study has been taken up to investigate the aetiopathology of ulcers of oral cavity and oropharynx. Methods: 60 cases of ulcers of oral cavity and oropharynx were included in the study. The aetiopathology of ulcers of oral cavity and oropharynx were investigated on the basis of age, sex, duration, etiological factors, symptom Index, socioeconomic status and anatomical distribution. Values are expressed as percentages. Results: The highest incidence was found to be in low socioeconomic group, where there is lack of education, improper food habits, cultivation of bad habits in early childhood and negligence of the disease are the predisposing factors in most of the malignancies. The highest incidence was found in low socioeconomic status. The lesions studied in this study were 50% of non-specific ulcers (Short term (3 wks 10-33%, 15% of Aphthous ulcers, 8.3% of Traumatic Ulcers, 6.5% of Malignant ulcers, 6.5% of Dental ulcers, 3.2% of HIV infection & AIDS, 3.2% of ulcer due to T.B. and 6.5% of ulcers. The majority of the cases were between the age 21-30 yrs constituting 35% followed by 11-12 years constituting 26.6%.d 62% of the short term ulcers, Female 38%. Conclusions: Low socioeconomic status, lack of education, bad oral hygiene, bad habits cultivated in early childhood is predisposing factors. Hence early diagnosis and prompt treatment is advised in all cases of ulcers. [Int J Res Med Sci 2014; 2(1.000: 180-185

  18. The psychological profile of parents who volunteer their children for clinical research: a controlled study.

    Science.gov (United States)

    Harth, S C; Johnstone, R R; Thong, Y H

    1992-06-01

    Three standard psychometric tests were administered to parents who volunteered their children for a randomised, double-blind placebo-controlled trial of a new asthma drug and to a control group of parents whose children were eligible for the trial but had declined the invitation. The trial took place at a children's hospital in Australia. The subjects comprised 68 parents who had volunteered their children and 42 who had not, a participation rate of 94 per cent and 70 per cent, respectively. The responses of these parents to the Gordon Survey of Interpersonal Values Questionnaire, the Coopersmith Self-Esteem Inventory and the Cattell Sixteen Personality Factor Questionnaire were analysed by computer. There was a marked difference between the psychological profiles of the two groups of parents. Volunteering parents put more value on benevolence while non-volunteering parents were more concerned with power and prestige. The self-esteem of volunteering parents was much lower than that of non-volunteering parents. Finally, volunteering parents were more introverted, exhibited greater anxiety and low supergo, while non-volunteering parents appeared to have greater social confidence and emotional stability. Since an individual's values, self-esteem and personality may be important antecedents of behaviour, these findings suggest that parents who volunteer their children for clinical research are not only socially disadvantaged and emotionally vulnerable, but may also be psychologically predisposed to volunteering. Furthermore, these findings provide evidence for the existence of a psychosocial 'filter' effect of the informed consent procedure, which may be discouraging the better educated, more privileged and psychologically resilient members of society from participation as research subjects. PMID:1619628

  19. A clinical profile of patients with Parkinson′s disease and psychosis

    Directory of Open Access Journals (Sweden)

    B. R. Amar

    2014-01-01

    Full Text Available Aims: The aim of the study was to study the clinical profile of the patients with Parkinson′s disease (PD and psychosis. Settings and Design: This was a prospective, cross sectional, hospital-based study done at the Department of Neurology, National Institute of Mental Health and Neurosciences, Bangalore, India from September 2009 to January 2011. All patients with PD, diagnosed by United Kingdom PD Society Brain Bank criteria, having with features of psychosis as diagnosed by the neuropsychiatric inventory (NPI were included. Patients without a caregiver who could validate the patient′s symptoms were excluded. Results: A total of 40 patients (5 women, 35 men with PD with psychosis (mean age: 54.2 ± 11.5 years, mean duration of illness: 6.5 ± 4.5 years, and mean duration of psychosis: 4.3 ± 4.3 years were included in the study. The Global NPI score was 19.1 ± 11.5. Majority of the patients had pure hallucinations (85%, while the rest had either pure delusions (7.5% or a combination of delusions and hallucinations (7.5%. In those with hallucinations, visual hallucinations were the commonest (60% (pure only in 22.5%, followed by auditory (45%, minor hallucinations (45%, and tactile (20%. Only one person reported having olfactory hallucinations (2.5%. Loss of insight was most often observed during the visual hallucinations (52%, followed by tactile (44.4%, auditory (38.9 %, and minor hallucinations (33.3%. Conclusions: In patients with PD and psychosis, pure hallucinations are common and visual hallucinations are the commonest among the hallucinations. A large proportion of patients have minor hallucinations, which need to be recognized early for effective and early management. The limitations of the study were small sample size, use of a single scale to assess psychosis and subjective assessment of insight.

  20. Clinical profile of hypertension at a University Teaching Hospital in Nigeria

    Directory of Open Access Journals (Sweden)

    Arthur C Onwuchekwa

    2010-07-01

    Full Text Available Arthur C Onwuchekwa, Sunday ChinenyeDepartment of Internal Medicine, University of Port Harcourt Teaching Hospital, NigeriaBackground: Hypertension in Nigeria is a widespread problem of immense social and economic importance because of its high prevalence and the severity of its complications.Aim: To define the morbidity and mortality pattern of hypertension at the University of Port Harcourt Teaching Hospital (UPTH.Method: Records of all patients admitted to the medical wards of the UPTH over a 5-year period with essential hypertension or any of its complications were retrieved from the ward and medical records and reviewed.Result: A total of 780 hypertensive patients were reviewed, constituting 28.2% of all ­medical admissions. Only 424 (15.2% had complete records and were analyzed. Record keeping was poor. There were 173 (41% males and 251 (59% females with a male to female ratio of 1:1.5. The ages ranged from 18 years to 100 years with a mean of 56.5 ± 16.2. Stroke was responsible for 169 (39.9% hypertensive complications. Heart failure occurred in 97 (22% cases while renal failure and encephalopathy accounted for 40 (9.4% and 7 (1.7% hypertensive complications respectively. There were 99 deaths out of which 51 (51.5% were due to stroke, 14 (14.12% were due to heart failure, and 12 (12.1% were due to renal failure.Conclusion: The contribution of systemic hypertension to the morbidity and mortality of adults at UPTH is quite significant.Keywords: clinical profile, hypertension, University of Port Harcourt Teaching Hospital

  1. Molecular pathology in lung cancer: a guide to the techniques used in clinical practice.

    Science.gov (United States)

    Walsh, Kathy; Wallace, William A

    2014-12-01

    Five year survival rates for lung cancer patients are poor; however the development of new therapeutic options, which benefit subsets of the population, offer hope of improvement. These novel therapies frequently rely upon the analysis of biomarkers in pathology samples; in lung cancer patients, testing is now routinely carried out to identify small mutations and chromosomal rearrangements in order to predict response to treatment. The recent increase in biomarker analyses in pathology samples has lead to the development of a new specialty, molecular pathology. The use of molecular pathology assays in clinical samples is largely under the control of the histopathologist; who is likely to be asked, as a minimum, to select tissue sections for molecular analysis and mark areas of H&E stained slides for macro or microdissection. Many histopathologists will also be involved in the sourcing and implementation of new assays. This review aims to provide a guide to some of the most commonly used molecular pathology methods - their advantages and their limitations.

  2. Expression profiling of a genetic animal model of depression reveals novel molecular pathways underlying depressive-like behaviours.

    Directory of Open Access Journals (Sweden)

    Ekaterini Blaveri

    Full Text Available BACKGROUND: The Flinders model is a validated genetic rat model of depression that exhibits a number of behavioural, neurochemical and pharmacological features consistent with those observed in human depression. PRINCIPAL FINDINGS: In this study we have used genome-wide microarray expression profiling of the hippocampus and prefrontal/frontal cortex of Flinders Depression Sensitive (FSL and control Flinders Depression Resistant (FRL lines to understand molecular basis for the differences between the two lines. We profiled two independent cohorts of Flinders animals derived from the same colony six months apart, each cohort statistically powered to allow independent as well as combined analysis. Using this approach, we were able to validate using real-time-PCR a core set of gene expression differences that showed statistical significance in each of the temporally distinct cohorts, representing consistently maintained features of the model. Small but statistically significant increases were confirmed for cholinergic (chrm2, chrna7 and serotonergic receptors (Htr1a, Htr2a in FSL rats consistent with known neurochemical changes in the model. Much larger gene changes were validated in a number of novel genes as exemplified by TMEM176A, which showed 35-fold enrichment in the cortex and 30-fold enrichment in hippocampus of FRL animals relative to FSL. CONCLUSIONS: These data provide significant insights into the molecular differences underlying the Flinders model, and have potential relevance to broader depression research.

  3. Expression profiling of blood samples from an SU5416 Phase III metastatic colorectal cancer clinical trial: a novel strategy for biomarker identification

    Directory of Open Access Journals (Sweden)

    Smolich Beverly D

    2003-02-01

    Full Text Available Abstract Background Microarray-based gene expression profiling is a powerful approach for the identification of molecular biomarkers of disease, particularly in human cancers. Utility of this approach to measure responses to therapy is less well established, in part due to challenges in obtaining serial biopsies. Identification of suitable surrogate tissues will help minimize limitations imposed by those challenges. This study describes an approach used to identify gene expression changes that might serve as surrogate biomarkers of drug activity. Methods Expression profiling using microarrays was applied to peripheral blood mononuclear cell (PBMC samples obtained from patients with advanced colorectal cancer participating in a Phase III clinical trial. The PBMC samples were harvested pre-treatment and at the end of the first 6-week cycle from patients receiving standard of care chemotherapy or standard of care plus SU5416, a vascular endothelial growth factor (VEGF receptor tyrosine kinase (RTK inhibitor. Results from matched pairs of PBMC samples from 23 patients were queried for expression changes that consistently correlated with SU5416 administration. Results Thirteen transcripts met this selection criterion; six were further tested by quantitative RT-PCR analysis of 62 additional samples from this trial and a second SU5416 Phase III trial of similar design. This method confirmed four of these transcripts (CD24, lactoferrin, lipocalin 2, and MMP-9 as potential biomarkers of drug treatment. Discriminant analysis showed that expression profiles of these 4 transcripts could be used to classify patients by treatment arm in a predictive fashion. Conclusions These results establish a foundation for the further exploration of peripheral blood cells as a surrogate system for biomarker analyses in clinical oncology studies.

  4. Description Model of Warehouse Architecture for Clinical Test at the Molecular Immunology Centre

    Directory of Open Access Journals (Sweden)

    Anthony Rafael Sotolongo León

    2012-05-01

    Full Text Available Accurate and detailed description of the architecture of computer systems is very important to achieve success in their development. As informatic solutions, data warehouses and software support decision-making in institutions that need to implement a detailed description of the architecture. Ralph Kimball proposes the aspects to be considered of the description and explains how it is done. There are specific models used to describe the architecture such as Kruchten 4 +1 views of meta-model or the Common Warehouse Metamodel (CWM however these models do not meet the need of the description that requires a data warehouse that integrates information from clinical trials of the Molecular Immunology Centre (CIM. In this paper we propose a model for describing the data warehouse architecture that fits the needs of the Molecular Immunology Center following the Kimball framework and using as UML 2.0 modeling language.

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

    Science.gov (United States)

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

    2014-03-01

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

  6. Classifications within molecular subtypes enables identification of BRCA1/BRCA2 mutation carriers by RNA tumor profiling.

    Directory of Open Access Journals (Sweden)

    Martin J Larsen

    Full Text Available Pathogenic germline mutations in BRCA1 or BRCA2 are detected in less than one third of families with a strong history of breast cancer. It is therefore expected that mutations still remain undetected by currently used screening methods. In addition, a growing number of BRCA1/2 sequence variants of unclear pathogen significance are found in the families, constituting an increasing clinical challenge. New methods are therefore needed to improve the detection rate and aid the interpretation of the clinically uncertain variants. In this study we analyzed a series of 33 BRCA1, 22 BRCA2, and 128 sporadic tumors by RNA profiling to investigate the classification potential of RNA profiles to predict BRCA1/2 mutation status. We found that breast tumors from BRCA1 and BRCA2 mutation carriers display characteristic RNA expression patterns, allowing them to be distinguished from sporadic tumors. The majority of BRCA1 tumors were basal-like while BRCA2 tumors were mainly luminal B. Using RNA profiles, we were able to distinguish BRCA1 tumors from sporadic tumors among basal-like tumors with 83% accuracy and BRCA2 from sporadic tumors among luminal B tumors with 89% accuracy. Furthermore, subtype-specific BRCA1/2 gene signatures were successfully validated in two independent data sets with high accuracies. Although additional validation studies are required, indication of BRCA1/2 involvement ("BRCAness" by RNA profiling could potentially be valuable as a tool for distinguishing pathogenic mutations from benign variants, for identification of undetected mutation carriers, and for selecting patients sensitive to new therapeutics such as PARP inhibitors.

  7. Serum Protein Profile Study of Clinical Samples Using High Performance Liquid Chromatography-Laser Induced Fluorescence

    DEFF Research Database (Denmark)

    Karemore, Gopal Raghunath; Ukendt, Sujatha; Rai, Lavanya;

    2009-01-01

    The serum protein profiles of normal subjects, patients diagnosed with cervical cancer, and oral cancer were recorded using High Performance Liquid Chromatography combined with Laser Induced Fluorescence detection (HPLC-LIF). Serum protein profiles of the above three classes were tested...

  8. Male breast cancer: An update in diagnosis, treatment and molecular profiling

    OpenAIRE

    Onami, Susan; Ozaki, Melanie; Mortimer, Joanne E; Pal, Sumanta Kumar

    2010-01-01

    Significant advances have been made in the diagnosis and treatment of female breast cancer, resulting in a decline in incidence and a global improvement in clinical outcome. The statistics for male breast cancer (MBC) stand in sharp contrast – over the past several decades, there has been a steady rise in the incidence of this disease, and clinical outcome has improved at a much slower pace. In the current review, the clinicopathologic features of MBC are described in detail. An emphasis is p...

  9. Prediction of Clinical Outcomes by Chemokine and Cytokine Profiling In CSF from Radiation Treated Breast Cancer Primary with Brain Metastases

    Science.gov (United States)

    Lok, Edwin

    Whole brain radiation is the standard treatment for patients with brain metastasis but unfortunately tumors can recover from radiation-induced damage with the help of the immune system. The hypothesis that differences in immunokines in the cerebrospinal fluid (CSF) pre- and post-irradiation could reveal tumor biology and correlate with outcome of patients with metastatic breast cancer to the brain is tested. Collected CSF samples were analyzed using Luminex's multiplexing assays to survey global immunokine levels while Enzyme-Linked Immunosorbent Assays were used to quantify each individual immunokines. Cluster analysis was performed to segregate patients based on their common immunokine profile and each cluster was correlated with survival and other clinical parameters. Breast cancer brain metastasis was found to have altered immunokine profiles in the CSF, and that Interleukin-1α expression was elevated after irradiation. Therefore, immunokine profiling in the CSF could enable cancer physicians to monitor the status of brain metastases.

  10. Using pathology-specific laboratory profiles in Clinical Pathology to reduce inappropriate test requesting: two completed audit cycles

    Directory of Open Access Journals (Sweden)

    Baricchi Roberto

    2012-07-01

    Full Text Available Abstract Background Systematic reviews have shown that, although well prepared, the Consensus Guidelines have failed to change clinical practice. In the healthcare district of Castelnovo né Monti (Reggio Emilia, Italy, it became necessary for the GPs and Clinical Pathologists to work together to jointly define laboratory profiles. Methods Observational study with two cycles of retrospective audit on test request forms, in a primary care setting. Objectives of the study were to develop pathology-specific laboratory profiles and to increase the number of provisional diagnoses on laboratory test request forms. A Multiprofessional Multidisciplinary Inter-hospital Work Team developed pathology-specific laboratory profiles for more effective test requesting. After 8 training sessions that used a combined strategy with multifaceted interventions, the 23 General Practitioners (GPs in the trial district (Castelnovo nè Monti tested the profiles; the 21 GPs in the Puianello district were the control group; all GPs in both districts participated in the trial. All laboratory tests for both healthcare districts are performed at the Laboratory located in the trial district. A baseline and a 1-year audit were performed in both districts on the GPs’ request forms. Results Seven pathology-specific laboratory profiles for outpatients were developed. In the year after the first audit cycle: 1 the number of tests requested in the trial district was distinctly lower than that in the previous year, with a decrease of about 5% (p  Conclusions The first audit cycle showed a significant decrease in the number of tests ordered only in the trial district. The combined strategy used in this study improved the prescriptive compliance of most of the GPs involved. The presence of the clinical pathologist is seen as an added value.

  11. Molecular profiling of peripheral blood cells from patients with polycythemia vera and related neoplasms

    DEFF Research Database (Denmark)

    Skov, V.; Thomassen, Mads; Kruse, T.A.;

    2012-01-01

    Essential thrombocythemia (ET), polycythemia vera (PV) and primary myelofibrosis (PMF) are hematopoietic stem cell neoplasms that may be associated with autoimmune or chronic inflammatory disorders. Earlier gene expression profiling studies have demonstrated aberrant expression of genes involved in...... chronic inflammation to be of pathogenetic importance for the progression of these neoplasms toward the myelofibrotic end-stage and may also account for the increased frequency of second cancer in these diseases. © 2012 Elsevier Ltd....

  12. Molecular Expression Profile Reveals Potential Biomarkers and Therapeutic Targets in Canine Endometrial Lesions

    OpenAIRE

    Fabiana Azevedo Voorwald; Fabio Albuquerque Marchi; Rolando Andre Rios Villacis; Carlos Eduardo Fonseca Alves; Gilson Hélio Toniollo; Renee Laufer Amorim; Sandra Aparecida Drigo; Silvia Regina Rogatto

    2015-01-01

    Cystic endometrial hyperplasia (CEH), mucometra, and pyometra are common uterine diseases in intact dogs, with pyometra being a life threatening disease. This study aimed to determine the gene expression profile of these lesions and potential biomarkers for closed-cervix pyometra, the most severe condition. Total RNA was extracted from 69 fresh endometrium samples collected from 21 healthy female dogs during diestrus, 16 CEH, 15 mucometra and 17 pyometra (eight open and nine closed-cervixes)....

  13. Recommendations for standardizing glucose reporting and analysis to optimize clinical decision making in diabetes: the Ambulatory Glucose Profile (AGP).

    Science.gov (United States)

    Bergenstal, Richard M; Ahmann, Andrew J; Bailey, Timothy; Beck, Roy W; Bissen, Joan; Buckingham, Bruce; Deeb, Larry; Dolin, Robert H; Garg, Satish K; Goland, Robin; Hirsch, Irl B; Klonoff, David C; Kruger, Davida F; Matfin, Glenn; Mazze, Roger S; Olson, Beth A; Parkin, Christopher; Peters, Anne; Powers, Margaret A; Rodriguez, Henry; Southerland, Phil; Strock, Ellie S; Tamborlane, William; Wesley, David M

    2013-03-01

    Abstract Underutilization of glucose data and lack of easy and standardized glucose data collection, analysis, visualization, and guided clinical decision making are key contributors to poor glycemic control among individuals with type 1 diabetes. An expert panel of diabetes specialists, facilitated by the International Diabetes Center and sponsored by the Helmsley Charitable Trust, met in 2012 to discuss recommendations for standardization of analysis and presentation of glucose monitoring data, with the initial focus on data derived from CGM systems. The panel members were introduced to a universal software report, the Ambulatory Glucose Profile (AGP), and asked to provide feedback on its content and functionality, both as a research tool and in clinical settings. This paper provides a summary of the topics and issues discussed during the meeting and presents recommendations from the expert panel regarding the need to standardize glucose profile summary metrics and the value of a uniform glucose report to aid clinicians, researchers, and patients.

  14. Recommendations for standardizing glucose reporting and analysis to optimize clinical decision making in diabetes: the ambulatory glucose profile.

    Science.gov (United States)

    Bergenstal, Richard M; Ahmann, Andrew J; Bailey, Timothy; Beck, Roy W; Bissen, Joan; Buckingham, Bruce; Deeb, Larry; Dolin, Robert H; Garg, Satish K; Goland, Robin; Hirsch, Irl B; Klonoff, David C; Kruger, Davida F; Matfin, Glenn; Mazze, Roger S; Olson, Beth A; Parkin, Christopher; Peters, Anne; Powers, Margaret A; Rodriguez, Henry; Southerland, Phil; Strock, Ellie S; Tamborlane, William; Wesley, David M

    2013-01-01

    Underutilization of glucose data and lack of easy and standardized glucose data collection, analysis, visualization, and guided clinical decision making are key contributors to poor glycemic control among individuals with type 1 diabetes mellitus. An expert panel of diabetes specialists, facilitated by the International Diabetes Center and sponsored by the Helmsley Charitable Trust, met in 2012 to discuss recommendations for standardizing the analysis and presentation of glucose monitoring data, with the initial focus on data derived from continuous glucose monitoring systems. The panel members were introduced to a universal software report, the Ambulatory Glucose Profile, and asked to provide feedback on its content and functionality, both as a research tool and in clinical settings. This article provides a summary of the topics and issues discussed during the meeting and presents recommendations from the expert panel regarding the need to standardize glucose profile summary metrics and the value of a uniform glucose report to aid clinicians, researchers, and patients.

  15. Molecular abundance profiles characterization of Jupiter'satmosphere using ground-based observations at 5 microns

    Science.gov (United States)

    Doriann, Blain; Fouchet, Thierry; Encrenaz, Therese A.; Drossart, Pierre; Greathouse, Thomas K.; Fletcher, Leigh N.; Orton, Glenn S.

    2016-10-01

    We report on early results of an observational campaign to support the Juno mission. At the beginning of this year, using TEXES (Texas Echelon cross-dispersed Echelle Spectrograph), mounted on the NASA Infrared Telescope Facility (IRTF), we obtained maps of Jupiter in several spectral ranges between 1800 and 2200 cm-1 which probes the atmosphere in the 1-4 bar region, with a spectral resolution of R ≈ 7000 and an angular resolution of ≈ 1.5''. This dataset is analyzed by a code which combines a line-by-line radiative transfer model with a non-linear optimal estimation inversion method. The inversion takes into account the abundance profiles of AsH3 , CO, GeH4 and H2O, as well as clouds contribution, in addtion to the abundance profiles of NH3 and PH3 . We will present the inverted abundance profiles, their significance for the understanding of Jupiter's atmospheric dynamics, and how they will be useful for the determination of water abundance up to 200 bars, which is one of the main objectives of the instrument MWR (MicroWave Radiometer) mounted on the Juno spacecraft. This work will also be useful to prepare the analysis of the JIRAM (Jovian InfraRed Auroral Mapper) 5-microns data aboard Juno.

  16. Molecular characterization and virulence gene profiling of pathogenic Streptococcus agalactiae populations from tilapia (Oreochromis sp.) farms in Thailand.

    Science.gov (United States)

    Kayansamruaj, Pattanapon; Pirarat, Nopadon; Katagiri, Takayuki; Hirono, Ikuo; Rodkhum, Channarong

    2014-05-19

    Streptococcus spp. were recovered from diseased tilapia in Thailand during 2009-2010 (n = 33), and were also continually collected from environmental samples (sediment and water) from tilapia farms for 9 months in 2011 (n = 25). The relative percent recovery of streptococci from environmental samples was 13-67%. All streptococcal isolates were identified as S. agalactiae (group B streptococci [GBS]) by a species-specific polymerase chain reaction. In molecular characterization assays, 4 genotypic categories comprised of 1) molecular serotypes, 2) the infB allele, 3) virulence gene profiling patterns (cylE, hylB, scpB, lmb, cspA, dltA, fbsA, fbsB, bibA, gap, and pili backbone-encoded genes), and 4) randomly amplified polymorphic DNA (RAPD) fingerprinting patterns, were used to describe the genotypic diversity of the GBS isolates. There was only 1 isolate identified as molecular serotype III, while the others were serotype Ia. Most GBS serotype Ia isolates had an identical infB allele and virulence gene profiling patterns, but a large diversity was established by RAPD analysis with diversity tending to be geographically dependent. Experimental infection of Nile tilapia (Oreochromis niloticus) revealed that the GBS serotype III isolate was nonpathogenic in the fish, while all 5 serotype Ia isolates (3 fish and 2 environmental isolates) were pathogenic, with a median lethal dose of 6.25-7.56 log10 colony-forming units. In conclusion, GBS isolates from tilapia farms in Thailand showed a large genetic diversity, which was associated with the geographical origins of the bacteria. PMID:24842288

  17. Survey of socio-economic profile of p seen at the dental clinic of University das Cruzes and of the treatment to w were submitted to: endodontic clinic

    Directory of Open Access Journals (Sweden)

    Maria Renata Giazzi NASSRI

    2009-09-01

    Full Text Available Introduction:In order to minimize the population oral health problemsis essential the consistent collection of information about the socio-economic situation and oral condition, raising the knowledge base thatwill lead the action, research and planning for better care. Objective:This article aimed to evaluate the socio-economic profile of patients seen at the endodontic clinic of UMC and its correlation with endodontic diseases.Material and methods: It was proposed a questionnaire to collect data through medical records of patients seen at the Endodontic Clinic of UMC.The study analyzed medical records of 70 patients,most of them female adult with age ranging from 22 to 69 years.Results:Most of the people attending the clinic of UMC has low-income, and it has been found that the most frequent cause of the endodontic problems is dental caries, followed by trauma.The largest number of diagnoses pointed to pulpal necrosis as a cause of endodontic involvement.Conclusion: It was concluded that the socio-economic profile of patients attending the clinic is of classes D and C (according to IBGE,and the leading cause of demand for endodontic treatment is pain.

  18. Translating molecular medicine into clinical tools: doomed to fail by neglecting basic preanalytical principles

    Directory of Open Access Journals (Sweden)

    Mannello Ferdinando

    2009-10-01

    Full Text Available Abstract This commentary discusses a study on measurements of matrix metalloproteinase 9 (MMP-9 in serum of pseudoxanthoma elasticum patients recently published in Journal of Molecular Medicine. This study can be considered the typical "obstacle" to effective translational medicine as previously documented in JTM journal. Although serum has been frequently proven as inappropriate sample for determining numerous circulating MMPs, among them MMP-9, there are over and over again studies, as in this case, that measure MMP-9 in serum. Comparative measurements in serum and plasma samples demonstrated higher concentrations for MMP-9 in serum due to the additional release from leukocytes and platelets following the coagulation/fibrinolysis process. From this example it can be concluded that translating basic research discoveries into clinical tools needs a more intensive exchange between basic biomedical research and clinical scientists already in an early stage. Otherwise a lost of translation, as discussed in JTM journal, seems to be inevitable.

  19. INHALED NITRIC OXIDE: CLINICAL EFFECTS AND INFLUENCE ON THE PROFILE OF INFLAMMATORY MARKERS IN PATIENTS WITH IDIOPATHIC PULMONARY HYPERTENSION

    OpenAIRE

    T. V. Martynyuk; S. N. Nakonechnikov; V P Masenko; I. E. Chazova

    2015-01-01

    Aim. To study the effect of treatment with inhaled nitric oxide (iNO) on the clinical status of patients with idiopathic pulmonary hypertension (IPH), and the profile of proinflammatory cytokines in peripheral blood. Material and methods. Patients with IPH (n=48) were included into the study. Evaluation of the IPH functional class (FC), the 6-minute walk test (6MWT) with the assessment of the Borg index, echocardiography , laboratory tests [blood count, evaluation of high-sensitivity C-reacti...

  20. Clinical profile of dengue fever infection in patients admitted in tertiary care centre Agroha, Hisar, Haryana, India

    OpenAIRE

    Mohd Younus Shah; Mohd Mubarak Naqash; Goel, R.K.; Deepak Galhan; Sunil Kumar; Vivek Chhabra; Abhishek Saini; K. L. Jaggal

    2016-01-01

    Background: Dengue infections can result in a wide spectrum of disease severity ranging from an influenza-like illness (dengue fever; DF) to the life-threatening dengue hemorrhagic fever (DHF)/dengue shock syndrome (DSS). The study was aimed to compare the clinical profile of all patients diagnosed with dengue viral infection at MAMC. Methods: This retrospective study included 188 patients infected with dengue virus, age 6 years to 70 years. Laboratory and haematological data were include...

  1. Clinical profile and post-operative lifestyle changes in cancer and non-cancer patients with ostomy

    OpenAIRE

    Anaraki, Fakhryalsadat; Vafaie, Mohamad; Behboo, Roobic; Maghsoodi, Nakisa; Esmaeilpour, Sahar; Safaee, Azadeh

    2012-01-01

    Aim The aim of this was to investigate some clinical profiles and lifestyle changes in stoma patients. Background Stoma patients experienced multiple complications due to their ostomy formation. Patients and methods A cross-sectional study performed on 102 random samples of stoma patients. Any patient with adequate physical and mental capability to participate and having had an ostomy in place for at least 3 months was eligible to enter the study. Participants asked to answer study questions ...

  2. Optimized high-throughput microRNA expression profiling provides novel biomarker assessment of clinical prostate and breast cancer biopsies

    OpenAIRE

    Fedele Vita; Scott Gary K; Wong Linda; Sensinger Kelly; Bowers Jessica; Benz Christopher C; Mattie Michael D; Ginzinger David; Getts Robert; Haqq Chris

    2006-01-01

    Abstract Background Recent studies indicate that microRNAs (miRNAs) are mechanistically involved in the development of various human malignancies, suggesting that they represent a promising new class of cancer biomarkers. However, previously reported methods for measuring miRNA expression consume large amounts of tissue, prohibiting high-throughput miRNA profiling from typically small clinical samples such as excision or core needle biopsies of breast or prostate cancer. Here we describe a no...

  3. Optimized high-throughput microRNA expression profiling provides novel biomarker assessment of clinical prostate and breast cancer biopsies

    Directory of Open Access Journals (Sweden)

    Fedele Vita

    2006-06-01

    Full Text Available Abstract Background Recent studies indicate that microRNAs (miRNAs are mechanistically involved in the development of various human malignancies, suggesting that they represent a promising new class of cancer biomarkers. However, previously reported methods for measuring miRNA expression consume large amounts of tissue, prohibiting high-throughput miRNA profiling from typically small clinical samples such as excision or core needle biopsies of breast or prostate cancer. Here we describe a novel combination of linear amplification and labeling of miRNA for highly sensitive expression microarray profiling requiring only picogram quantities of purified microRNA. Results Comparison of microarray and qRT-PCR measured miRNA levels from two different prostate cancer cell lines showed concordance between the two platforms (Pearson correlation R2 = 0.81; and extension of the amplification, labeling and microarray platform was successfully demonstrated using clinical core and excision biopsy samples from breast and prostate cancer patients. Unsupervised clustering analysis of the prostate biopsy microarrays separated advanced and metastatic prostate cancers from pooled normal prostatic samples and from a non-malignant precursor lesion. Unsupervised clustering of the breast cancer microarrays significantly distinguished ErbB2-positive/ER-negative, ErbB2-positive/ER-positive, and ErbB2-negative/ER-positive breast cancer phenotypes (Fisher exact test, p = 0.03; as well, supervised analysis of these microarray profiles identified distinct miRNA subsets distinguishing ErbB2-positive from ErbB2-negative and ER-positive from ER-negative breast cancers, independent of other clinically important parameters (patient age; tumor size, node status and proliferation index. Conclusion In sum, these findings demonstrate that optimized high-throughput microRNA expression profiling offers novel biomarker identification from typically small clinical samples such as breast

  4. Clinical and molecular aspects of the live attenuated Oka varicella vaccine.

    Science.gov (United States)

    Quinlivan, Mark; Breuer, Judy

    2014-07-01

    VZV is a ubiquitous member of the Herpesviridae family that causes varicella (chicken pox) and herpes zoster (shingles). Both manifestations can cause great morbidity and mortality and are therefore of significant economic burden. The introduction of varicella vaccination as part of childhood immunization programs has resulted in a remarkable decline in varicella incidence, and associated hospitalizations and deaths, particularly in the USA. The vaccine preparation, vOka, is a live attenuated virus produced by serial passage of a wild-type clinical isolate termed pOka in human and guinea pig cell lines. Although vOka is clinically attenuated, it can cause mild varicella, establish latency, and reactivate to cause herpes zoster. Sequence analysis has shown that vOka differs from pOka by at least 42 loci; however, not all genomes possess the novel vOka change at all positions, creating a heterogeneous population of genetically distinct haplotypes. This, together with the extreme cell-associated nature of VZV replication in cell culture and the lack of an animal model, in which the complete VZV life cycle can be replicated, has limited studies into the molecular basis for vOka attenuation. Comparative studies of vOka with pOka replication in T cells, dorsal root ganglia, and skin indicate that attenuation likely involves multiple mutations within ORF 62 and several other genes. This article presents an overview of the clinical aspects of the vaccine and current progress on understanding the molecular mechanisms that account for the clinical phenotype of reduced virulence. PMID:24687808

  5. International conference on clinical PET and molecular nuclear medicine (IPET 2007). Book of abstracts

    International Nuclear Information System (INIS)

    The International Atomic Energy Agency is organizing its first international conference on 'Clinical PET and Molecular Nuclear Medicine'. Medical imaging technologies have undergone explosive growth over the past two decades. Today, imaging is at a crossroad, with molecular targeted imaging agents expected to broadly expand the capabilities of conventional anatomical imaging methods. Observing molecular interactions in the living body by the radiotracer technique has become known as 'molecular nuclear medicine'. Molecular nuclear medicine techniques analyze cellular biochemistry and its relationship to disease processes expressed in tissue and organ dysfunction, for diagnostic and therapeutic purposes. People can often have similar manifestations of disease, but no two patients will be the same. Functional radionuclide imaging and positron emission tomography (PET) provide excellent opportunities to follow the pathology in individual patients and therefore provide a means for tailored clinical management. These also provide the means to assess the response to treatment in a safe and non-invasive manner. Changes at molecular and cellular levels provide vital clues for evaluating the effectiveness of chosen clinical treatment plans. This information is expected to have a major impact on understanding disease, disease detection, individualised treatment, and drug development. Recently, considerable attention has been drawn to nuclear medicine with the visualization of biochemical processes in vivo such as PET studies with 18F-FDG in many different organs and in cancerous tissues. With the arrival of PET/CT systems there is a new era of accurate mapping of disease processes. Today, 18F-FDG is the most useful PET tracer for the detection, staging, treatment planning and management of cancer. There is mounting evidence for its competitive advantage over conventional techniques in major medical areas including oncology, cardiology, and neurology. Nuclear medicine is

  6. Premature ovarian failure (POF) syndrome: towards the molecular clinical analysis of its genetic complexity.

    Science.gov (United States)

    Fassnacht, W; Mempel, A; Strowitzki, T; Vogt, P H

    2006-01-01

    The Premature Ovarian Failure (POF) syndrome is a very heterogeneous clinical disorder due probably to the complex genetic networks controlling human folliculogenesis. Clinical subgroups of POF patients whose aetiology of ovarian failure is based on the same genetic factors are therefore difficult to establish. Some experimental evidence suggests that these genes might be clustered on the female sex chromosome in the POF1 and POF2 loci. This review is aimed to present an overview of the actual structural changes of the X chromosome causing POF, and to present a number of X and autosomal female fertility genes which are probably key genes in human folliculogenesis and are therefore prominent POF candidate genes. Towards the molecular analysis of their functional contribution to the genetic aetiology of POF in the clinic, an interdisciplinary scheme for their diagnostic analysis is presented in a pilot study focussed on chromosome analyses and the expression analysis of some major POF candidate genes (DAZL, DBX, FOXL2, INHalpha, GDF9, USP9X) in the leukocytes of 101 POF patients. It starts with a comprehensive and significantly improved clinical diagnostic program for this large and heterogeneous patient group.

  7. Molecular characterisation of clinical and environmental isolates of Mycobacterium kansasii isolates from South African gold mines.

    Science.gov (United States)

    Kwenda, Geoffrey; Churchyard, Gavin J; Thorrold, Catherine; Heron, Ian; Stevenson, Karen; Duse, Adriano G; Marais, Elsé

    2015-03-01

    Mycobacterium kansasii (M. kansasii) is a major cause of non-tuberculous mycobacterial pulmonary disease in the South African gold-mining workforce, but the source of infection and molecular epidemiology are unknown. This study investigated the presence of M. kansasii in gold and coal mine and associated hostel water supplies and compared the genetic diversity of clinical and environmental isolates of M. kansasii. Five M. kansasii and ten other potentially pathogenic mycobacteria were cultured mainly from showerhead biofilms. Polymerase chain reaction-restriction analysis of the hsp65 gene on 196 clinical and environmental M. kansasii isolates revealed 160 subtype I, eight subtype II and six subtype IV strains. Twenty-two isolates did not show the typical M. kansasii restriction patterns, suggesting that these isolates may represent new subtypes of M. kansasii. In contrast to the clonal population structure found amongst the subtype I isolates from studies in other countries, DNA fingerprinting of 114 clinical and three environmental subtype I isolates demonstrated genetic diversity amongst the isolates. This study demonstrated that showerheads are possible sources of M. kansasii and other pathogenic non-tuberculous mycobacterial infection in a gold-mining region, that subtype I is the major clinical isolate of M. kansasii strain and that this subtype exhibits genetic diversity. PMID:25719478

  8. The electrostatic potential profile along a biased molecular wire A model quantum mechanical calculation

    CERN Document Server

    Pleutin, S; Ingold, G L; Nitzan, A; Pleutin, St\\'ephane; Grabert, Hermann; Ingold, Gert-Ludwig; Nitzan, Abraham

    2003-01-01

    We study the electrostatic potential of a molecular wire bridging two metallic electrodes in the limit of weak contacts. With the use of a tight-binding model including a fully three-dimensional treatment of the electrostatics of the molecular junction, the potential is shown to be poorly screened, dropping mostly along the entire molecule. In addition, we observe pronounced Friedel oscillations that can be related to the breaking of electron-hole symmetry. Our results are in semi-quantitative agreement with recent state-of-the-art ab initio calculations and point to the need of a three-dimensional treatment to properly capture the behavior of the electrostatic potential. Based on these results, current-voltage curves are calculated within the Landauer formalism. It is shown that Coulomb interaction partially compensates the localization of the charges induced by the electric field and consequently tends to suppress zones of negative differential resistance.

  9. Clinical applications of schizophrenia genetics: genetic diagnosis, risk, and counseling in the molecular era

    Directory of Open Access Journals (Sweden)

    Costain G

    2012-02-01

    Full Text Available Gregory Costain1,2, Anne S Bassett1–41Clinical Genetics Research Program, Centre for Addiction and Mental Health, 2Institute of Medical Science, University of Toronto, 3Division of Cardiology, Department of Medicine and Department of Psychiatry, University Health Network, 4Department of Psychiatry, University of Toronto, Toronto, Ontario, CanadaAbstract: Schizophrenia is a complex neuropsychiatric disease with documented clinical and genetic heterogeneity, and evidence for neurodevelopmental origins. Driven by new genetic technologies and advances in molecular medicine, there has recently been concrete progress in understanding some of the specific genetic causes of this serious psychiatric illness. In particular, several large rare structural variants have been convincingly associated with schizophrenia, in targeted studies over two decades with respect to 22q11.2 microdeletions, and more recently in large-scale, genome-wide case-control studies. These advances promise to help many families afflicted with this disease. In this review, we critically appraise recent developments in the field of schizophrenia genetics through the lens of immediate clinical applicability. Much work remains in translating the recent surge of genetic research discoveries into the clinic. The epidemiology and basic genetic parameters (such as penetrance and expression of most genomic disorders associated with schizophrenia are not yet well characterized. To date, 22q11.2 deletion syndrome is the only established genetic subtype of schizophrenia of proven clinical relevance. We use this well-established association as a model to chart the pathway for translating emerging genetic discoveries into clinical practice. We also propose new directions for research involving general genetic risk prediction and counseling in schizophrenia.Keywords: schizophrenia, genetics, 22q11 deletion syndrome, copy number variation, genetic counseling, genetic predisposition to disease

  10. In vitro chemosensitivity profile of oral squamous cell cancer and its correlation with clinical response to chemotherapy

    Directory of Open Access Journals (Sweden)

    Pathak K

    2007-01-01

    Full Text Available Context : Oral cancers represent a disparate group of tumors with diverse clinical behavior and chemosensitivity profile. Currently, it is difficult to predict whether a tumor will respond to chemotherapy and which drug(s will achieve the maximum clinical response. Aims : To study in vitro chemosensitivity profile of oral cancers and to correlate the in vitro chemosensitivity of oral cancer to clinical response to chemotherapy. Settings and Design : Prospective study in a tertiary cancer care center. Methods and Material : We prospectively studied the chemosensitivity profile of 57 untreated, advanced, unresectable oral cancers to cisplatin, methotrexate, 5-fluorouracil and their combinations by using histoculture drug response assay (HDRA and correlated them to the clinical response to chemotherapy. Statistical Analysis Used : Chi Square test. Results : Biopsy samples were successfully histocultured in 52/57 (91% cases. Of these 52 evaluable patients, 47 had primary gingivo-buccal cancers and five had tongue / floor of mouth cancers. Based on the assay, 27 (52% tumors were sensitive to cisplatin, 27 (52% to methotrexate, 24 (46% to 5-fluorouracil, 38 (73% to combination of cisplatin and methotrexate and 36 (69% to combination of cisplatin and 5-fluorouracil. Of these, 31 patients with good performance status received two cycles of chemotherapy using one or more of these test drugs. There was a significant correlation (p=0.03 between the in vitro chemosensitivity and the clinical response. Negative predictive value of the test was 80%, positive predictive value-69%, sensitivity-79% and specificity -71%. The overall accuracy of the assay was 74%. Conclusions : We found HDRA to be a fairly good predictor of chemo-response of oral cancer.

  11. Spironolactone in the treatment of polycystic ovary syndrome: effects on clinical features, insulin sensitivity and lipid profile.

    Science.gov (United States)

    Zulian, E; Sartorato, P; Benedini, S; Baro, G; Armanini, D; Mantero, F; Scaroni, C

    2005-01-01

    This prospective clinical trial was designed to assess the effects of a long-term therapy with spironolactone, with and without dietary-induced weight-loss, on clinical features, lipid profile and insulin levels in women with polycystic ovary syndrome (PCOS). Twenty-five patients (range of age 16-32 yr; 13 lean and 12 overweight) fulfilling formal diagnostic criteria for PCOS (oligomenorrhea and/or amenorrhea, biochemical and/or clinical evidence of hyperadrogenism) were studied at baseline and then received oral spironolactone (100 mg/die) for 12 months; association with lifestyle modifications was recommended to all over-weight patients. Clinical, endocrine and metabolic parameters [oral glucose tolerance test (OGTT), lipid profile] were measured at baseline and at the end of the antiandrogen treatment. The therapy was associated with a significant average decline of triglycerides in overweight subjects and with increased HDL-cholesterol levels in lean patients. The insulin levels at 60 min during OGTT, homeostasis model assessment-insulin resistance and area under curve of insulin were significantly lowered in overweight women after 12 months of spironolactone and weight loss and no negative changes in insulin secretion and sensitivity were observed in PCOS women after pharmacological treatment alone. The efficacy of spironolactone on the androgenic clinical aspects of PCOS has been confirmed in this study. Furthermore, our data show that long-term treatment with spironolactone exerts no negative effects on lipoprotein profile and glucose metabolism; more relevant beneficial effects on glucose and lipid metabolism were observed when the antiandrogen was associated with weight loss in overweight PCOS women. PMID:15816371

  12. Molecular and epidemiological profiles of hepatitis C virus genotype 4 in Denmark

    DEFF Research Database (Denmark)

    Eriksen, Mette Brandt; Jørgensen, Louise Bruun; Krarup, Henrik;

    2010-01-01

    patients (22%) were infected with subtypes 4h, 4k, 4l, 4n, 4o, or 4Unclassified. Three epidemiological profiles were identified: (1) patients infected with HCV by intravenous drug use were infected solely with subtype 4d. They were all of European origin, and 15 of the 16 patients were ethnic Danes...... East. (3) Patients from Southern Africa dominated among patients infected with subtype 4r (10 of 12 patients). This study demonstrates that HCV genotype 4d has been introduced in and spread among Danish intravenous drug users. The remaining subtypes show restricted distribution, infecting almost...

  13. Clinical and molecular characterization of two patients with palmoplantar keratoderma-congenital alopecia syndrome type 2.

    Science.gov (United States)

    Castori, M; Morlino, S; Sana, M E; Paradisi, M; Tadini, G; Angioni, A; Malacarne, M; Grammatico, P; Iascone, M; Forzano, F

    2016-08-01

    Palmoplantar keratoderma-congenital alopecia (PPKCA) syndrome is a rare genodermatosis, with two clinically recognizable forms: dominant (Type 1) and recessive (Type 2). Reports of only 18 patients have been published to date, and the molecular basis of the condition is unknown. We describe two cases with PPKCA Type 2 (PPKCA2), comprising a novel patient, originally reported as an example of autosomal ichthyosis follicularis-atrichia-photophobia syndrome, and the 6-year follow-up of a previously published case. Extensive molecular studies of both patients excluded mutations in all the known genes associated with PPK and partially overlapping syndromes. The striking similarities between these two patients confirm PPKCA2 as a discrete genodermatosis, of which the main features are congenital and universal alopecia, diffuse keratosis pilaris, facial erythema, and a specific PPK with predominant involvement of the fingertips and borders of the hands and feet, with evolution of sclerodactyly, contractures and constrictions. Clinical follow-up of these patients has demonstrated progressive worsening of the hand involvement and attenuation of facial erythema. PMID:27339777

  14. A clinical-molecular update on azanucleoside-based therapy for the treatment of hematologic cancers.

    Science.gov (United States)

    Diesch, Jeannine; Zwick, Anabel; Garz, Anne-Kathrin; Palau, Anna; Buschbeck, Marcus; Götze, Katharina S

    2016-01-01

    The azanucleosides azacitidine and decitabine are currently used for the treatment of acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) in patients not only eligible for intensive chemotherapy but are also being explored in other hematologic and solid cancers. Based on their capacity to interfere with the DNA methylation machinery, these drugs are also referred to as hypomethylating agents (HMAs). As DNA methylation contributes to epigenetic regulation, azanucleosides are further considered to be among the first true "epigenetic drugs" that have reached clinical application. However, intriguing new evidence suggests that DNA hypomethylation is not the only mechanism of action for these drugs. This review summarizes the experience from more than 10 years of clinical practice with azanucleosides and discusses their molecular actions, including several not related to DNA methylation. A particular focus is placed on possible causes of primary and acquired resistances to azanucleoside treatment. We highlight current limitations for the success and durability of azanucleoside-based therapy and illustrate that a better understanding of the molecular determinants of drug response holds great potential to overcome resistance. PMID:27330573

  15. Microphthalmia with linear skin defects (MLS) syndrome: Clinical, cytogenetic, and molecular characterization

    Energy Technology Data Exchange (ETDEWEB)

    Lindsay, E.A.; Grillo, A.; Ferrero, G.B.; Baldini, A.; Ballabio, A.; Zoghbi, H.Y.; Roth, E.J. [Baylor College of Medicine, Houston, TX (United States); Magenis, E.; Grompe, M. [Oregon Health Science Univ., Portland, OR (United States); Hulten, M. [East Birmingham Hospital, Birmingham (United Kingdom)] [and others

    1994-01-15

    The microphthalmia with linear skin defects (MLS) syndrome (MIM309801) is a severe developmental disorder observed in XX individuals with distal Xp segmental monosomy. The phenotype of this syndrome overlaps with that of both Aicardi (MIM 305050) and Goltz (MIM 305600) syndromes, two X-linked dominant, male-lethal disorders. Here the authors report the clinical, cytogenetic, and molecular characterization of 3 patients with this syndrome. Two of these patients are females with a terminal Xpter-p22.2 deletion. One of these 2 patients had an aborted fetus with anencephaly and the same chromosome abnormality. The third patient is an XX male with Xp/Yp exchange spanning the SRY gene which results in distal Xp monosomy. The extensive clinical variability observed in these patients and the results of the molecular analysis suggest that X-inactivation plays an important role in determining the phenotype of the MLS syndrome. The authors propose that the MLS, Aicardi, and Goltz syndromes are due to the involvement of the same gene(s), and that different patterns of X-inactivation are responsible for the phenotypic differences observed in these 3 disorders. However, they cannot rule out that each component of the MLS phenotype is caused by deletion of a different gene (a contiguous gene syndrome). 24 refs., 4 figs., 1 tab.

  16. Study of correlation of thyroid profile and clinical parameters in patients with infertility

    Directory of Open Access Journals (Sweden)

    Kameswaramma K.

    2016-05-01

    Conclusions: Every infertile woman with ovulatory dysfunction should also investigated thyroid profile along with other investigations, to open better prospects for such desperate infertile women. [Int J Reprod Contracept Obstet Gynecol 2016; 5(5.000: 1410-1413

  17. Clinical and demographic profile of HIV/AIDS patients diagnosed at a tertiary care centre in Kashmir

    International Nuclear Information System (INIS)

    Objectives: To study the clinical and demographic profile of HIV/AIDS patients diagnosed at a tertiary care centre. Methods: The study was conducted on a group of 1141 patients suspected of having HIV/AIDS on clinical grounds. Screening was done using different Elisa's as advised by NACO and those confirmed as HIV positive were studied for their clinical spectrum and different demographic parameters. Results: Out of 1141 patients tested, 26 proved to have HIV 1 infection with no case of HIV 2 detected. Mean age of presentation was 40.04 +- 7 years, main age group affected 31-40 years and a male: female ratio of 4.2:1 was observed. More than 42% were non Kashmiris with armed forces outnumbering all other occupational classes. Heterosexual transmission was the commonest with married out numbering unmarried. Fever, asthenia and weight loss were the predominant symptoms and pulmonary tuberculosis and oropharyngeal candidiasis commonest opportunistic infections. Conclusion: The clinical and demographic profile of HIV/AIDS patients in Kashmir is largely similar to the rest of India. Kashmir no longer stands immune to the menace of HIV/AIDS. With increasing globalization, frequent travel and change in social values the state is likely to witness an alarming rise in new cases unless a multi pronged approach is undertaken to control the spread. (author)

  18. A profile of prognostic and molecular factors in European and Māori breast cancer patients

    International Nuclear Information System (INIS)

    New Zealand Māori have a poorer outcome from breast cancer than non-Māori, yet prognostic data are sparse. The objective of this study was to quantify levels of prognostic factors in a cohort of self-declared Māori and European breast cancer patients from Christchurch, New Zealand. Clinicopathological and survival data from 337 consecutive breast cancer patients (27 Māori, 310 European) were evaluated. Fewer tumours were high grade in Māori women than European women (p = 0.027). No significant ethnic differences were detected for node status, tumour type, tumour size, human epidermal growth factor receptor, oestrogen and progesterone receptor (ER/PR) status, or survival. In addition, tumour and serum samples from a sub-cohort of 14 Māori matched to 14 NZ European patients were analyzed by immunohistochemistry and enzyme linked immunosorbent assay for molecular prognostic factors. Significant correlations were detected between increased grade and increased levels of hypoxia inducible factor-1 (HIF-1α), glucose transporter-1 (GLUT-1), microvessel density (MVD) and cytokeratins CK5/6 (p < 0.05). High nodal status correlated with reduced carbonic anhydrase IX (CA-IX). Negative ER/PR status correlated with increased GLUT-1, CA-IX and MVD. Within the molecular factors, increased HIF-1α correlated with raised GLUT-1, MVD and CK5/6, and CK5/6 with GLUT-1 and MVD (p < 0.05). The small number of patients in this sub-cohort limited discrimination of ethnic differences. In this Christchurch cohort of breast cancer patients, Māori women were no more likely than European women to have pathological or molecular factors predictive of poor prognosis. These data contrast with data from the North Island NZ, and suggest potential regional differences

  19. PO02 - Clinical profile of children admitted to a paediatric intensive care unit due to acute clinical deterioration

    DEFF Research Database (Denmark)

    Jensen, Claus Sixtus; Aagaard, Hanne; Olesen, Hanne Vebert;

    2016-01-01

    Theme: Intensive care Background: There has been an increased number of critically ill patients admitted to paediatric departments. Only a few studies have described the various causes of unplanned admission to paediatric intensive care units (PICU) due to clinical deterioration. However, an...... critical ill children in paediatric wards....

  20. Molecular and clinical analysis of Ellis-van Creveld syndrome in the United Arab Emirates

    Directory of Open Access Journals (Sweden)

    Rahmani Aiman

    2010-02-01

    Full Text Available Abstract Background Ellis-van Creveld (EvC syndrome is an autosomal recessive chondrodysplastic condition with clinical manifestations that include short-limbs and ribs, postaxial polydactyly and dysplastic nails and teeth. In about two thirds of patients, mutations in either EVC or EVC2 genes have been found to be the underlying cause. Methods In this paper, we describe the molecular (DNA sequencing and clinical analysis of six children diagnosed with EvC from four different families from the United Arab Emirates (UAE. Results All the children had the common clinical and radiological features of this syndrome. However, DNA sequence analysis of the genes shown to be involved (EVC and EVC2 revealed a novel splice site mutation (c.2047-1G>T in intron 13 of EVC2 gene in one family. In addition, we confirm previous mutational analyses that showed a truncating mutation in exon 13 of EVC gene (c.1813C>T; p.Q605X in the second family and a single nucleotide deletion (c.981delG; p.K327fs in exon 8 of EVC2 gene in the third family. No mutations in the exons, splice sites or the promoter regions of either gene have been found in the index case of the fourth family who exhibited "EvC-like" features. Conclusions Given the small population size of UAE, our data illustrates further the molecular heterogeneity observed in EvC patients and excludes the possibility of a common founder effect for this condition in the UAE reflecting the current ethnic diversity of the country.

  1. The Clinical Development of Molecularly Targeted Agents in Combination With Radiation Therapy: A Pharmaceutical Perspective

    International Nuclear Information System (INIS)

    Summary: This paper explores historical and current roles of pharmaceutical industry sponsorship of clinical trials testing radiation therapy combinations with molecularly targeted agents and attempts to identify potential solutions to expediting further combination studies. An analysis of clinical trials involving a combination of radiation therapy and novel cancer therapies was performed. Ongoing and completed trials were identified by searching the (clinicaltrials.gov) Web site, in the first instance, with published trials of drugs of interest identified through American Society of Clinical Oncology, European CanCer Organisation/European Society for Medical Oncology, American Society for Radiation Oncology/European Society for Therapeutic Radiology and Oncology, and PubMed databases and then cross-correlated with (clinicaltrials.gov) protocols. We examined combination trials involving radiation therapy with novel agents and determined their distribution by tumor type, predominant molecular mechanisms examined in combination to date, timing of initiation of trials relative to a novel agent's primary development, and source of sponsorship of such trials. A total of 564 studies of targeted agents in combination with radiation therapy were identified with or without concomitant chemotherapy. Most studies were in phase I/II development, with only 36 trials in phase III. The tumor site most frequently studied was head and neck (26%), followed by non-small cell lung cancer. Pharmaceutical companies were the sponsors of 33% of studies overall and provided support for only 16% of phase III studies. In terms of pharmaceutical sponsorship, Genentech was the most active sponsor of radiation therapy combinations (22%), followed by AstraZeneca (14%). Most radiation therapy combination trials do not appear to be initiated until after drug approval. In phase III studies, the most common (58%) primary endpoint was overall survival. Collectively, this analysis suggests that such

  2. Real-time molecular profiling of photochemically induced rat thrombosis in vivo through quantitative Raman analysis of blood

    Science.gov (United States)

    Lin, M. M.; Shen, A. G.; Yao, H. L.; Zhang, Z. Z.; Hu, J. M.

    2014-11-01

    A device of an animal thrombosis model in vivo coupled with a Raman system for near-surface blood vessels is proposed in this letter. The dual-function set up is capable of simultaneously establishing a photochemically induced artificial thrombus model and collecting in vivo Raman data of both arterial and venous blood, and it provides the first observation of rat thrombosis under the physiological conditions from the beginning to the final form. The real-time and quantitative molecular profiling of flowing blood and the spectra of blood cells in the process of thrombosis provides an insight into the occurring mechanism of thrombosis and a promising method for the in vivo screening of new antithrombotic and thrombolytic drugs.

  3. Real-time molecular profiling of photochemically induced rat thrombosis in vivo through quantitative Raman analysis of blood

    International Nuclear Information System (INIS)

    A device of an animal thrombosis model in vivo coupled with a Raman system for near-surface blood vessels is proposed in this letter. The dual-function set up is capable of simultaneously establishing a photochemically induced artificial thrombus model and collecting in vivo Raman data of both arterial and venous blood, and it provides the first observation of rat thrombosis under the physiological conditions from the beginning to the final form. The real-time and quantitative molecular profiling of flowing blood and the spectra of blood cells in the process of thrombosis provides an insight into the occurring mechanism of thrombosis and a promising method for the in vivo screening of new antithrombotic and thrombolytic drugs. (letter)

  4. RNA profiling reveals familial aggregation of molecular subtypes in non-BRCA1/2 breast cancer families

    DEFF Research Database (Denmark)

    Larsen, Martin J; Thomassen, Mads; Tan, Qihua;

    2014-01-01

    BACKGROUND: In more than 70% of families with a strong history of breast and ovarian cancers, pathogenic mutation in BRCA1 or BRCA2 cannot be identified, even though hereditary factors are expected to be involved. It has been proposed that tumors with similar molecular phenotypes also share similar...... underlying pathophysiological mechanisms. In the current study, the aim was to investigate if global RNA profiling can be used to identify functional subgroups within breast tumors from families tested negative for BRCA1/2 germline mutations and how these subgroupings relate to different breast cancer...... cancer subtypes, exist among non-BRCA1/2 breast cancers. The distribution of subtypes was markedly different from the distribution found among BRCA1/2 mutation carriers. From 11 breast cancer families, breast tumor biopsies from more than one affected family member were included in the study. Notably...

  5. Molecular Characterization and Antimicrobial Resistance Profile of Methicillin-Resistant Staphylococcus aureus in Retail Chicken.

    Science.gov (United States)

    Sallam, Khalid Ibrahim; Abd-Elghany, Samir Mohammed; Elhadidy, Mohamed; Tamura, Tomohiro

    2015-10-01

    The emergence of livestock-associated methicillin-resistant Staphylococcus aureus (MRSA) in food-producing animals is of increasing interest, raising questions about the presence of MRSA in food of animal origin and potential sources of transmission to humans via the food chain. In this study, the prevalence, molecular characterization, virulence factors, and antimicrobial susceptibility patterns of MRSA isolates from 200 retail raw chicken samples in Egypt were determined. MRSA was detected by positive amplification of the mecA gene in 38% (76 of 200) of chicken samples analyzed. This represents a potential public health threat in Egypt, as this contamination rate seems to be the highest among other studies reported worldwide. Furthermore, genes encoding α-hemolysin (hla) and staphylococcal enterotoxins (sea, seb, and sec) were detected in all of the 288 MRSA isolates. Nonetheless, none of the strains tested carried tst, the gene encoding toxic shock syndrome toxin 1. Antimicrobial resistance of MRSA isolates was most frequently detected against penicillin (93.4%), ampicillin (88.9%), and cloxacillin (83.3%). These results suggest that retail chicken might be a significant potential source for transmission of multidrug-resistant and toxigenic S. aureus in Egypt. This underlines the need for stricter hygienic measures in chicken production in Egypt to minimize the risk of transmission of these strains to consumers. To the best of our knowledge, this is the first study that reports the isolation and molecular characterization of MRSA in retail chicken samples in Egypt.

  6. Relationship of molecular weight distribution profile of unreduced gluten protein extracts with quality characteristics of bread.

    Science.gov (United States)

    Chaudhary, Nisha; Dangi, Priya; Khatkar, B S

    2016-11-01

    A statistical correlation was established among the molecular weight distribution patterns of unreduced gluten proteins and physicochemical, rheological and bread-making quality characteristics of wheat varieties. Size exclusion chromatography fractionated the gluten proteins apparently into five peaks. Peak I signified glutenins (30-130kDa), peak II as gliadins (20-55kDa), peak III as very low molecular weight monomeric gliadins (10-28kDa), peak IV and V, collectively, as albumins and globulins (gluten index (r=0.959(∗∗)), and gliadin/glutenin ratio (r=-0.952(∗∗)), while peak II influenced inversely as expected. Peak I exhibited positive statistical significance with bread loaf volume (r=0.848(∗∗)); however, peak II had negative (r=-0.818(∗∗)) impact. Bread firmness increased with increment in peak II (r=0.625(∗∗)), and decreased with accretion in peak I (r=-0.623(∗∗)). PMID:27211654

  7. Molecular Profiling of the Lateral Habenula in a Rat Model of Depression

    DEFF Research Database (Denmark)

    Christensen, Trine; Bouzinova, Elena; Wiborg, Ove

    2013-01-01

    habenula of rats subjected to chronic mild stress (mild stressors exchanged twice a day for 8 weeks). Some rats received antidepressant treatment during fifth to eights week of CMS. The lateral habenula gene expression profile was studied through the gene ontology and signal pathway analyses using......Objective. This study systematically investigated the effect of chronic mild stress and response to antidepressant treatment in the lateral habenula at the whole genome level. Methods. Rat whole genome expression chips (Affymetrix) were used to detect gene expression regulations in the lateral...... bioinformatics. Real-time quantitative polymerase chain reaction (RT-PCR) was used to verify the microarray results and determine the expression of the Fcrla, Eif3k, Sec3l1, Ubr5, Abca8a, Ankrd49, Cyp2j10, Frs3, Syn2, and Znf503 genes in the lateral habenula tissue. Results. In particular we found that stress...

  8. Molecular characterization of BZR transcription factor family and abiotic stress induced expression profiling in Brassica rapa.

    Science.gov (United States)

    Saha, Gopal; Park, Jong-In; Jung, Hee-Jeong; Ahmed, Nasar Uddin; Kayum, Md Abdul; Kang, Jong-Goo; Nou, Ill-Sup

    2015-07-01

    BRASSINAZOLE-RESISTANT (BZR) transcription factors (TFs) are primarily well known as positive regulators of Brassinosteroid (BR) signal transduction in different plants. BR is a plant specific steroid hormone, which has multiple stress resistance functions besides various growth regulatory roles. Being an important regulator of the BR synthesis, BZR TFs might have stress resistance related activities. However, no stress resistance related functional study of BZR TFs has been reported in any crop plants so far. Therefore, this study identified 15 BZR TFs of Brassica rapa (BrBZR) from a genome-wide survey and characterized them through sequence analysis and expression profiling against several abiotic stresses. Various systematic in silico analysis of these TFs validated the fundamental properties of BZRs, where a high degree of similarity also observed with recognized BZRs of other plant species from the comparison studies. In the organ specific expression analyses, 6 BrBZR TFs constitutively expressed in flower developmental stages indicating their flower specific functions. Subsequently, from the stress resistance related expression profiles differential transcript abundance levels were observed by 6 and 11 BrBZRs against salt and drought stresses, respectively. All BrBZRs showed several folds up-regulation against exogenous ABA treatment. All BrBZRs also showed differential expression against low temperature stress treatments and these TFs were proposed as transcriptional activators of CBF cold response pathway of B. rapa. Notably, three BrBZRs gave co-responsive expression against all the stresses tested here, suggesting their multiple stress resistance related functions. Thus, the findings would be helpful in resolving the complex regulatory mechanism of BZRs in stress resistance and further functional genomics study of these potential TFs in different Brassica crops. PMID:25931321

  9. Molecular subtype profiling of invasive breast cancers weakly positive for estrogen receptor.

    Science.gov (United States)

    Sheffield, Brandon S; Kos, Zuzana; Asleh-Aburaya, Karama; Wang, Xiu Qing; Leung, Samuel; Gao, Dongxia; Won, Jennifer; Chow, Christine; Rachamadugu, Rakesh; Stijleman, Inge; Wolber, Robert; Gilks, C Blake; Myles, Nickolas; Thomson, Tom; Hayes, Malcolm M; Bernard, Philip S; Nielsen, Torsten O; Chia, Stephen K L

    2016-02-01

    The estrogen receptor (ER) is a key predictive biomarker in the treatment of breast cancer. There is uncertainty regarding the use of hormonal therapy in the setting of weakly positive ER by immunohistochemistry (IHC). We report intrinsic subtype classification on a cohort of ER weakly positive early-stage breast cancers. Consecutive cases of breast cancer treated by primary surgical resection were retrospectively identified from 4 centers that engage in routine external proficiency testing for breast biomarkers. ER-negative (Allred 0 and 2) and ER weakly positive (Allred 3-5) cases were included. Gene expression profiling was performed using qRT-PCR. Intrinsic subtype prediction was made based upon the PAM50 gene expression signature. 148 cases were included in the series: 60 cases originally diagnosed as ER weakly positive and 88 ER negative. Of the cases originally assessed as ER weakly positive, only 6 (10 %) were confirmed to be of luminal subtype by gene expression profiling; the remaining 90 % of cases were classified as basal-like or HER2-enriched subtypes. This was not significantly different than the fraction of luminal cases identified in the IHC ER-negative cohort (5 (5 %) luminal, 83(95 %) non-luminal). Recurrence-free, and overall, survival rates were similar in both groups (p = 0.4 and 0.5, respectively) despite adjuvant hormonal therapy prescribed in the majority (59 %) of weakly positive ER cases. Weak ER expression by IHC is a poor correlate of luminal subtype in invasive breast cancer. In the setting of highly sensitive and robust IHC methodology, cutoffs for ER status determination and subsequent systemic therapy should be revisited. PMID:26846986

  10. A STUDY OF CLINICAL PROFILE, RADIOLOGICAL FEATURES, ELECTROCARDIOGRAPHIC AND ECHOCARDIOGRAPHIC CHANGES IN CHRONIC COR PULMONALE IN A RURAL HOSPITAL

    Directory of Open Access Journals (Sweden)

    Sunil Babu

    2013-11-01

    Full Text Available ABSTRACT: BACKGROUND AND OBJECTIVES: To study the clinical profile, radiological features, electrocardiographic and echocardiographic changes in clinically proven cases of chronic cor pulmonale. METHODS: 50 patients who were diagnosed to have chronic cor pulmonale based on the inclusion criteria were selected from the medical wards of Adichunchanagiri Hospital and research centre, over a period of 2 years In all the selected patients detailed history and physical examination was noted and chest x - ray PA, 1 2 lead ECG and echocardiogram done. RESULTS: Among 50 patients admitted with chronic cor pulmonale, 45 were males and 5 were females. The peak incidence was found in the 4 th , 5 th and 6 th decades of life. Smoking was found to be a major cause for COPD and h ence cor pulmonale. Among 50 patients 43 were smokers. Among 50 cases, (60% were diagnosed to have chronic bronchitis with or without emphysema. Chest x - ray showed details relevant to the clinical profile. ECG showed 46% cases with RVH, 64% with RAD, 26% RBBB and 70% with P pulmonale. Every patient showed echocardiographic features suggesting chronic cor pulmonale except 3 patients who showed global hypokinesia. DISCUSSION AND CONCLUSION: Many patients who had chronic cor pulmonale were found to have COPD as the underlying disease. Majority of the male patients were smokers in the present study. Echocardiogram was found to be a better diagnostic tool. Though ECG and chest x - ray can support the diagnosis, ECHO can be used as a non invasive, affordable invest igation for accurate and early diagnosis of chronic cor pulmonale KEYWORDS: Chronic cor pulmonale; Clinical profile; Chest x ray; ECG; Echocardiogram.

  11. Angiostrongylus cantonensis: a review of its distribution, molecular biology and clinical significance as a human pathogen.

    Science.gov (United States)

    Barratt, Joel; Chan, Douglas; Sandaradura, Indy; Malik, Richard; Spielman, Derek; Lee, Rogan; Marriott, Deborah; Harkness, John; Ellis, John; Stark, Damien

    2016-08-01

    Angiostrongylus cantonensis is a metastrongyloid nematode found widely in the Asia-Pacific region, and the aetiological agent of angiostrongyliasis; a disease characterized by eosinophilic meningitis. Rattus rats are definitive hosts of A. cantonensis, while intermediate hosts include terrestrial and aquatic molluscs. Humans are dead-end hosts that usually become infected upon ingestion of infected molluscs. A presumptive diagnosis is often made based on clinical features, a history of mollusc consumption, eosinophilic pleocytosis in cerebral spinal fluid, and advanced imaging such as computed tomography. Serological tests are available for angiostrongyliasis, though many tests are still under development. While there is no treatment consensus, therapy often includes a combination of anthelmintics and corticosteroids. Angiostrongyliasis is relatively rare, but is often associated with morbidity and sometimes mortality. Recent reports suggest the parasites' range is increasing, leading to fatalities in regions previously considered Angiostrongylus-free, and sometimes, delayed diagnosis in newly invaded regions. Increased awareness of angiostrongyliasis would facilitate rapid diagnosis and improved clinical outcomes. This paper summarizes knowledge on the parasites' life cycle, clinical aspects and epidemiology. The molecular biology of Angiostrongylus spp. is also discussed. Attention is paid to the significance of angiostrongyliasis in Australia, given the recent severe cases reported from the Sydney region. PMID:27225800

  12. Hyperornithinemia-hyperammonemia-homocitrullinuria syndrome with stroke-like imaging presentation: clinical, biochemical and molecular analysis.

    Science.gov (United States)

    Al-Hassnan, Zuhair N; Rashed, Mohamed S; Al-Dirbashi, Osama Y; Patay, Zoltan; Rahbeeni, Zuhair; Abu-Amero, Khaled K

    2008-01-15

    Hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome is an autosomal recessive disorder caused by mutations in ORNT1 gene that encodes a mitochondrial ornithine transporter. It has variable clinical presentations with episodic hyperammonemia, liver dysfunction, and chronic neurological manifestations. In this work, we report the findings of HHH syndrome in 3 Saudi siblings. The 4-year-old proband presented with recurrent Reye-like episodes, hypotonia, and multiple stroke-like lesions on brain MRI. Biochemical and molecular analysis confirmed that she had HHH syndrome. She significantly improved on protein restriction and sodium benzoate. Her two older siblings have milder phenotypes with protein intolerance and learning problems. In comparison to their sister, their homocitrulline and orotic acid were only mildly elevated even before treatment. The three patients were homozygous for a novel mutation in ORNT1 with a Gly220Arg change. In view of the CNS lesions, which initially were felt to be suggestive of MELAS, we sequenced the entire mtDNA genome and no potential pathogenic mutations were detected. Analysis of ORNT2 did not provide explanation of the clinical and biochemical variability. This work presents a yet unreported CNS involvement pattern, notably multiple supratentorial stroke-like lesions in association with HHH syndrome. Moreover, it illustrates considerable clinical/biochemical correlation, and describes a novel mutation. We suggest including HHH syndrome in the differential diagnosis of patients found to have stroke-like lesions on brain MRI.

  13. Molecular analysis and association with clinical and laboratory manifestations in children with sickle cell anemia

    Directory of Open Access Journals (Sweden)

    Roberta Faria Camilo-Araújo

    2014-10-01

    Full Text Available Objectives: To analyze the frequency of βS-globin haplotypes and alpha-thalassemia, and their influence on clinical manifestations and the hematological profile of children with sickle cell anemia. Method: The frequency of βS-globin haplotypes and alpha-thalassemia and any association with clinical and laboratorial manifestations were determined in 117 sickle cell anemia children aged 3–71 months. The confirmation of hemoglobin SS and determination of the haplotypes were achieved by polymerase chain reaction-restriction fragment length polymorphism, and alpha-thalassemia genotyping was by multiplex polymerase chain reaction (single-tube multiplex-polymerase chain reaction. Results: The genotype distribution of haplotypes was 43 (36.7% Central African Republic/Benin, 41 (35.0% Central African Republic/Central African Republic, 20 (17.0% Rare/atypical, and 13 (11.1% Benin/Benin. The frequency of the α3.7 deletion was 1.71% as homozygous (−α3.7/−α3.7 and 11.9% as heterozygous (−α3.7/αα. The only significant association in respect to haplotypes was related to the mean corpuscular volume. The presence of alpha-thalassemia was significantly associated to decreases in mean corpuscular volume, mean corpuscular hemoglobin and reticulocyte count and to an increase in the red blood cell count. There were no significant associations of βS-globin haplotypes and alpha-thalassemia with clinical manifestations. Conclusions: In the study population, the frequency of alpha-thalassemia was similar to published data in Brazil with the Central African Republic haplotype being the most common, followed by the Benin haplotype. βS-globin haplotypes and interaction between alpha-thalassemia and sickle cell anemia did not influence fetal hemoglobin concentrations or the number of clinical manifestations.

  14. The profile of patients followed at the Neuroimmunology Clinic at UNIFESP: 20 years analysis

    Directory of Open Access Journals (Sweden)

    Denis Bernardi Bichuetti

    2015-04-01

    Full Text Available Objective To describe the clinical activities at the Neuroimmunology Clinic of the Universidade Federal de São Paulo (UNIFESP from 1994 to 2013. Method The final diagnosis of all patients that attended the center was reviewed and established upon specific guidelines for each disease. The number of total appointments and extra clinical activities (reports and prescriptions were also analyzed, as are part of routine activities. Results 1,599 patients attended the Clinic from 1994 to 2013: 816 with multiple sclerosis (MS, 172 with clinical isolated syndromes, 178 with neuromyelitis optica (NMO, 216 with other demyelinating disease, 20 with metabolic disorder, 42 with a vascular disease and 155 with other or undetermined diagnosis. A mean 219 outpatient visits and 65 extra clinical activities were performed monthly. Conclusion We identified that 15% of patients seen have NMO. As patients with NMO have a more severe disease than MS, this data may be important for planning local health care policies.

  15. STUDY OF CLINICAL PROFILE OF DENGUE FEVER WITH SPECIAL REFERENCE TO ACUTE COMPLICATIONS

    OpenAIRE

    Keshava,; Chikkalingaiah; Guru3; Channappa

    2014-01-01

    ABSTRACT: Dengue is the arthropode borne viral infection transmitted by mosquitoes to humans. AIM: To study the various clinical manifestations and acute complications of dengue fever. METHODS: 100 cases of confirmed dengue infection admitted to KIMS, Bangalore between December 2009 and September 2011 were studied. A detailed clinical history and physical examination was done and baseline investigations were performed. The cases were followed-up daily for the clinical and laboratory parameter...

  16. Speciation of organic phosphorus in a sediment profile of Lake Taihu Ⅱ.Molecular species and their depth attenuation

    Institute of Scientific and Technical Information of China (English)

    Shiming Ding; Di Xu; Xiuling Bai; Shuchun Yao; Chengxin Fan; Chaosheng Zhang

    2013-01-01

    The understanding of organic phosphorus (P) dynamics in sediments requires information on their species at the molecular level,but such information in sediment profiles is scarce.A sediment profile was selected from a large eutrophic lake,Lake Taihu (China),and organic P species in the sediments were detected using solution phosphorus-31 nuclear magnetic resonance spectroscopy (31P NMR) following extraction of the sediments with a mixture of 0.25 mol/L NaOH and 50 mmol/L EDTA (NaOH-EDTA) solution.The results showed that P in the NaOH-EDTA extracts was mainly composed of orthophosphate,orthophosphate monoesters,phospholipids,DNA,and pyrophosphate.Concentrations of the major organic P compound groups and pyrophosphate showed a decreasing trend with the increase of depth.Their half-life times varied from 3 to 27 years,following the order of orthophosphate monoesters > phospholipids ≥ DNA > pyrophosphate.Principal component analysis revealed that the detected organic P species had binding phases similar to those of humic acid-associated organic P (NaOH-NRPHA),a labile organic P pool that tends to transform to recalcitrant organic P pools as the early diagenetic processes proceed.This demonstrated that the depth attenuation of the organic P species could be partly attributed to their increasing immobilization by the sediment solids,while their degradation rates should be significantly lower than what were suggested in previous studies.

  17. Assessment of changes in community level physiological profile and molecular diversity of bacterial communities in different stages of jute retting.

    Science.gov (United States)

    Das, Biswapriya; Chakrabarti, Kalyan; Ghosh, Sagarmoy; Chakraborty, Ashis; Saha, Manabendra Nath

    2013-12-01

    Retting of jute is essentially microbiological and biochemical in nature. Community Level Physiological Profiles (CLPP) as well as genomic diversity of bacterial communities were assessed in water samples collected during pre-retting, after 1st and 2nd charges of retting. The water samples were collected from two widely cultivated jute growing locations, Sonatikari (22 degrees 41'27"N; 88 degrees 35'44"E) and Baduria (22 degrees 44'24"N; 88 degrees 47'24"E), West Bengal, India. The CLPP, expressed as net area under substrate utilization curve, was studied by carbon source utilization patterns in BIOLOG Ecoplates. Molecular diversity was studied by polymerase chain reaction followed by denaturing gradient gel electrophoresis (PCR-DGGE) of total DNA from water samples. Both between locations and stages of retting, substrate utilizations pattern were carbohydrates > carboxylic acids > polymers > amino acids > amines/amides > phenolic compounds. Differential substrate utilization pattern as well as variation in banding pattern in DGGE profiles was observed between the two locations and at different stages of retting. The variations in CLPP in different stages of retting were due to the change in bacterial communities. PMID:24506039

  18. Relationship between clinical manifestations and pulsed-field gel profiles of Streptococcus canis isolates from dogs and cats.

    Science.gov (United States)

    Kruger, E Freya; Byrne, Barbara A; Pesavento, Patricia; Hurley, Kate F; Lindsay, Leanne L; Sykes, Jane E

    2010-11-20

    Little is known regarding the degree of genotypic relatedness between Streptococcus canis isolates from dogs and cats. The purpose of this study was to determine whether correlations existed between the genotypes of canine and feline S. canis isolates as determined using pulsed-field gel electrophoresis (PFGE) and different clinical manifestations of disease. Eighty-two isolates of S. canis were examined that had been collected from dogs and cats presenting to the University of California, Davis Veterinary Medical Teaching Hospital (VMTH) between 1998 and 2005. Associated clinical manifestations included sepsis, otitis, pyometra, skin infections, necrotizing fasciitis, respiratory disease, and urinary tract infections. In addition, 9 feline isolates from a southern California shelter that experienced an outbreak of S. canis infection manifesting as necrotizing fasciitis and death were examined. Bacterial isolates were characterized by PFGE analysis using the restriction enzyme SmaI. The relationships between banding patterns were analyzed using gel analysis software combined with visual interpretation. The feline shelter isolates of S. canis were 99% similar in bacterial PFGE profile. The remainder of samples had less than 80% similarity in PFGE banding patterns. The relatedness of the PFGE profile in the feline shelter isolates suggested a clonal origin. In the isolates from the VMTH population, there was no relationship between specific disease manifestations and PFGE profile. PFGE typing does not appear to be useful for identifying isolates associated with specific disease presentations; however may be more useful to identify outbreaks of S. canis infections or to detect clonal populations in outbreaks. PMID:20605376

  19. Comparative gene expression analysis throughout the life cycle of Leishmania braziliensis: diversity of expression profiles among clinical isolates.

    Directory of Open Access Journals (Sweden)

    Vanessa Adaui

    Full Text Available BACKGROUND: Most of the Leishmania genome is reported to be constitutively expressed during the life cycle of the parasite, with a few regulated genes. Inter-species comparative transcriptomics evidenced a low number of species-specific differences related to differentially distributed genes or the differential regulation of conserved genes. It is of uppermost importance to ensure that the observed differences are indeed species-specific and not simply specific of the strains selected for representing the species. The relevance of this concern is illustrated by current study. METHODOLOGY/PRINCIPAL FINDINGS: We selected 5 clinical isolates of L. braziliensis characterized by their diversity of clinical and in vitro phenotypes. Real-time quantitative PCR was performed on promastigote and amastigote life stages to assess gene expression profiles at seven time points covering the whole life cycle. We tested 12 genes encoding proteins with roles in transport, thiol-based redox metabolism, cellular reduction, RNA poly(A-tail metabolism, cytoskeleton function and ribosomal function. The general trend of expression profiles showed that regulation of gene expression essentially occurs around the stationary phase of promastigotes. However, the genes involved in this phenomenon appeared to vary significantly among the isolates considered. CONCLUSION/SIGNIFICANCE: Our results clearly illustrate the unique character of each isolate in terms of gene expression dynamics. Results obtained on an individual strain are not necessarily representative of a given species. Therefore, extreme care should be taken when comparing the profiles of different species and extrapolating functional differences between them.

  20. Toward Integrated Clinical and Gene- Expression Profiles For Breast Cancer Prognosis: A Review Paper

    Directory of Open Access Journals (Sweden)

    Farzana Kabir Ahmad

    2009-10-01

    Full Text Available Breast cancer patients with the same diagnostic and clinical prognostics profilecan have markedly different clinical outcomes. This difference is possibly causedby the limitation of current breast cancer prognostic indices, which groupmolecularly distinct patients into similar clinical classes based mainly on themorphology of diseases. Traditional clinical-based prognosis models werediscovered to contain some restrictions to address the heterogeneity of breastcancer. The invention of microarray technology and its ability to simultaneouslyinterrogate thousands of genes has changed the paradigm of molecularclassification of human cancers as well as shifting clinical prognosis models to abroader prospect. Numerous studies have revealed the potential value of geneexpressionsignatures in examining the risk of disease recurrence. However,most of these studies attempted to implement genetic-marker based prognosticmodels to replace the traditional clinical markers, yet neglecting the richinformation contained in clinical information. Therefore, this research took theeffort to integrate both clinical and microarray data in order to obtain accuratebreast cancer prognosis, by taking into account that these data complement eachother. This article presents a review of the development of breast cancerprognosis models, concentrating precisely on clinical and gene-expressionprofiles. The literature is reviewed in an explicit machine-learning framework,which includes the elements of feature selection and classification techniques.

  1. Molecular profiles of Quadriceps muscle in myostatin-null mice reveal PI3K and apoptotic pathways as myostatin targets

    Directory of Open Access Journals (Sweden)

    Hocquette Jean-François

    2009-04-01

    Full Text Available Abstract Background Myostatin (MSTN, a member of the TGF-β superfamily, has been identified as a negative regulator of skeletal muscle mass. Inactivating mutations in the MSTN gene are responsible for the development of a hypermuscular phenotype. In this study, we performed transcriptomic and proteomic analyses to detect altered expression/abundance of genes and proteins. These differentially expressed genes and proteins may represent new molecular targets of MSTN and could be involved in the regulation of skeletal muscle mass. Results Transcriptomic analysis of the Quadriceps muscles of 5-week-old MSTN-null mice (n = 4 and their controls (n = 4 was carried out using microarray (human and murine oligonucleotide sequences of 6,473 genes expressed in muscle. Proteomic profiles were analysed using two-dimensional gel electrophoresis coupled with mass spectrometry. Comparison of the transcriptomic profiles revealed 192 up- and 245 down- regulated genes. Genes involved in the PI3K pathway, insulin/IGF pathway, carbohydrate metabolism and apoptosis regulation were up-regulated. Genes belonging to canonical Wnt, calcium signalling pathways and cytokine-receptor cytokine interaction were down-regulated. Comparison of the protein profiles revealed 20 up- and 18 down-regulated proteins spots. Knockout of the MSTN gene was associated with up-regulation of proteins involved in glycolytic shift of the muscles and down-regulation of proteins involved in oxidative energy metabolism. In addition, an increased abundance of survival/anti-apoptotic factors were observed. Conclusion All together, these results showed a differential expression of genes and proteins related to the muscle energy metabolism and cell survival/anti-apoptotic pathway (e.g. DJ-1, PINK1, 14-3-3ε protein, TCTP/GSK-3β. They revealed the PI3K and apoptotic pathways as MSTN targets and are in favour of a role of MSTN as a modulator of cell survival in vivo.

  2. Molecular cloning and tissue distribution profiles of the chicken R-spondin1 gene.

    Science.gov (United States)

    Han, Y Q; Geng, J; Shi, H T; Zhang, X M; Du, L L; Liu, F T; Li, M M; Wang, X T; Wang, Y Y; Yang, G Y

    2015-01-01

    Rspo1 belongs to the Rspo family, which is composed of 4 members (Rspo1-4) that share 40 to 60% sequence homology and similar domain organizations, and regulate the WNT signaling pathway via a common mechanism. Rspo1 plays a key role in vertebrate development and is an effective mitogenic factor of gastrointestinal epithelial cells. We report the cloning of chicken Rspo1 and its gene expression distribution among tissues. It contained an open reading frame of 783 bp encoding a protein of 260 amino acids, and its molecular weight was predicted to be 28.80 kDa. Reverse transcription-polymerase chain reaction-based gene expression analysis indicated that chicken Rspo1 was highly expressed in the stomach muscle tissue, but was expressed at low levels in the lung, brain, jejunum, cecum, ileum, spleen, pancreas, kidney, and glandular stomach. These results suggest that Rspo1 plays a major role in muscular immune protection. PMID:25966073

  3. Transcriptome assembly and expression profiling of molecular responses to cadmium toxicity in hepatopancreas of the freshwater crab Sinopotamon henanense

    Science.gov (United States)

    Sun, Min; Ting Li, Yi; Liu, Yang; Chin Lee, Shao; Wang, Lan

    2016-01-01

    Cadmium (Cd) pollution is a serious global problem, which causes irreversible toxic effects on animals. Freshwater crab, Sinopotamon henanense, is a useful environmental indicator since it is widely distributed in benthic habitats whereby it tends to accumulate Cd and other toxicants. However, its molecular responses to Cd toxicity remain unclear. In this study, we performed transcriptome sequencing and gene expression analyses of its hepatopancreas with and without Cd treatments. A total of 7.78 G clean reads were obtained from the pooled samples, and 68,648 unigenes with an average size of 622 bp were assembled, in which 5,436 were metabolism-associated and 2,728 were stimulus response-associated that include 380 immunity-related unigenes. Expression profile analysis demonstrated that most genes involved in macromolecular metabolism, oxidative phosphorylation, detoxification and anti-oxidant defense were up-regulated by Cd exposure, whereas immunity-related genes were down-regulated, except the genes involved in phagocytosis were up-regulated. The current data indicate that Cd exposure alters gene expressions in a concentration-dependent manner. Therefore, our results provide the first comprehensive S.henanense transcriptome dataset, which is useful for biological and ecotoxicological studies on this crab and its related species at molecular level, and some key Cd-responsive genes may provide candidate biomarkers for monitoring aquatic pollution by heavy metals.

  4. A Molecular Profile of Cocaine Abuse Includes the Differential Expression of Genes that Regulate Transcription, Chromatin, and Dopamine Cell Phenotype

    Science.gov (United States)

    Bannon, Michael J; Johnson, Magen M; Michelhaugh, Sharon K; Hartley, Zachary J; Halter, Steven D; David, James A; Kapatos, Gregory; Schmidt, Carl J

    2014-01-01

    Chronic drug abuse, craving, and relapse are thought to be linked to long-lasting changes in neural gene expression arising through transcriptional and chromatin-related mechanisms. The key contributions of midbrain dopamine (DA)-synthesizing neurons throughout the addiction process provide a compelling rationale for determining the drug-induced molecular changes that occur in these cells. Yet our understanding of these processes remains rudimentary. The postmortem human brain constitutes a unique resource that can be exploited to gain insights into the pathophysiology of complex disorders such as drug addiction. In this study, we analyzed the profiles of midbrain gene expression in chronic cocaine abusers and well-matched drug-free control subjects using microarray and quantitative PCR. A small number of genes exhibited robust differential expression; many of these are involved in the regulation of transcription, chromatin, or DA cell phenotype. Transcript abundances for approximately half of these differentially expressed genes were diagnostic for assigning subjects to the cocaine-abusing vs control cohort. Identification of a molecular signature associated with pathophysiological changes occurring in cocaine abusers' midbrains should contribute to the development of biomarkers and novel therapeutic targets for drug addiction. PMID:24642598

  5. Quantitatively integrating molecular structure and bioactivity profile evidence into drug-target relationship analysis

    Directory of Open Access Journals (Sweden)

    Xu Tianlei

    2012-05-01

    Full Text Available Abstract Background Public resources of chemical compound are in a rapid growth both in quantity and the types of data-representation. To comprehensively understand the relationship between the intrinsic features of chemical compounds and protein targets is an essential task to evaluate potential protein-binding function for virtual drug screening. In previous studies, correlations were proposed between bioactivity profiles and target networks, especially when chemical structures were similar. With the lack of effective quantitative methods to uncover such correlation, it is demanding and necessary for us to integrate the information from multiple data sources to produce an comprehensive assessment of the similarity between small molecules, as well as quantitatively uncover the relationship between compounds and their targets by such integrated schema. Results In this study a multi-view based clustering algorithm was introduced to quantitatively integrate compound similarity from both bioactivity profiles and structural fingerprints. Firstly, a hierarchy clustering was performed with the fused similarity on 37 compounds curated from PubChem. Compared to clustering in a single view, the overall common target number within fused classes has been improved by using the integrated similarity, which indicated that the present multi-view based clustering is more efficient by successfully identifying clusters with its members sharing more number of common targets. Analysis in certain classes reveals that mutual complement of the two views for compound description helps to discover missing similar compound when only single view was applied. Then, a large-scale drug virtual screen was performed on 1267 compounds curated from Connectivity Map (CMap dataset based on the fused similarity, which obtained a better ranking result compared to that of single-view. These comprehensive tests indicated that by combining different data representations; an improved

  6. Clinical Profiles of Children with Disruptive Behaviors Based on the Severity of Their Conduct Problems, Callous-Unemotional Traits and Emotional Difficulties.

    Science.gov (United States)

    Andrade, Brendan F; Sorge, Geoff B; Na, Jennifer Jiwon; Wharton-Shukster, Erika

    2015-08-01

    This study identified clinical profiles of referred children based on the severity of callous-unemotional (CU) traits, emotional difficulties, and conduct problems. Parents of 166 children (132 males) aged 6-12 years referred to a hospital clinic because of disruptive behavior completed measures to assess these key indicators, and person-centered analysis was used to identify profiles. Four distinct profiles were identified that include: (1) Children low in severity on the three domains, (2) Children high in severity on the three domains, (3) Children high in severity in conduct problems and CU traits with minimal emotional difficulties, and (4) Children high in severity in conduct problems and emotional difficulties with minimal CU traits. Profiles differed in degree of aggression and behavioral impairment. Findings show that clinic-referred children with disruptive behaviors can be grouped based on these important indicators into profiles that have important implications for assessment and treatment selection. PMID:25257946

  7. Molecular profiling of signalling pathways in formalin-fixed and paraffin-embedded cancer tissues.

    Science.gov (United States)

    Berg, Daniela; Hipp, Susanne; Malinowsky, Katharina; Böllner, Claudia; Becker, Karl-Friedrich

    2010-01-01

    In most hospitals word-wide, histopathological cancer diagnosis is currently based on formalin-fixed and paraffin-embedded (FFPE) tissues. In the last few years new approaches and developments in patient-tailored cancer therapy have raised the need to select more precisely those patients, who will respond to personalised treatments. The most efficient way for optimal therapy and patient selection is probably to provide a tumour-specific protein network portrait prior to treatment. The discovery and characterisation of deregulated signalling molecules (e.g. human epidermal growth factor receptor 2, mitogen-activated protein kinases) are very promising candidates for the identification of new suitable therapy targets and for the selection of those patients who will receive the greatest benefit from individualised treatments. The reverse phase protein array (RPPA) is a promising new technology that allows quick, precise and simultaneous analysis of many components of a network. Importantly it requires only limited amounts of routine clinical material (e.g. FFPE biopsies) and can be used for absolute protein measurements. We and other research groups have described successful protein extraction from routine FFPE tissues. In this manuscript we show how these recent developments might facilitate the implementation of RPPA in clinical trials and routine settings.

  8. Ultrasensitive Mirco-Hall Detector for Enumeration and Molecular Profiling of Rare Cells

    Science.gov (United States)

    Min, Changwook; Issadore, David; Chung, Jaehoon; Shao, Huilin; Liong, Monty; Ghazani, Arezou A.; Castro, Cesar M.; Weissleder, Ralph; Lee, Hakho

    2013-03-01

    We have recently developed a miniaturized microfluidic chip-based technology, the micro-Hall detector (uHD), that can perform rapid, highly sensitive, and quantitative measurement of individual cells in unprocessed biological samples. The uHD detects the Hall voltage induced by magnetic moments of cells in-flow that have been immunomagnetically tagged with magnetic nanoparticles (MNPs) and bio-orthogonal chemistry. The entire assay is performed on a single microfluidic chip with minimal sample preparation to avoid sample loss and to simplify assay procedure, eliminating the need for any washing and purification steps, and thereby allows cellular diagnostics to be conducted in point-of-care clinical settings. We also demonstrated simultaneous detection of heterogeneous biomarkers on individual cells by targeting different cellular markers with a panel of MNPs. The quantity of each MNP type, and hence the expression level of a target biomarker in a single cell, could be obtained using the particles' distinctive magnetization properties. The clinical use of the uHD was explored by the detection of circulating tumor cells (CTCs) in whole blood of 20 ovarian cancer patients, and drug treatment efficacy was monitored in a mouse tumor model.