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Bhattacharya B Sariya D Reddy VB Kluskens L Gould VE Gattuso P 《Diagnostic cytopathology》2002,26(6):384-386
A 4(1/2)-yr-old female presented with right-sided pleural effusion and a retroperitoneal mass. Cytologic analysis of the pleural fluid yielded malignant small round blue cells, which were noncohesive, 3-4 times the size of lymphocytes. The malignant cells had hyperchromatic, pleomorphic nuclei with moderate amounts of vacuolated cytoplasm. A few fiber-shaped cells were also seen. Immunostains for desmin, muscle-specific actin were positive; ultrastructural findings of thick and thin actin-myosin filaments confirmed the diagnosis of embryonal rhabdomyosarcoma. This case illustrates the importance of performing appropriate immunohistochemical stains and ultrastructural studies on cytological material to arrive at a definitive diagnosis. 相似文献
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Leslie G. Biesecker James C. Mullikin Flavia M. Facio Clesson Turner Praveen F. Cherukuri Robert W. Blakesley Gerard G. Bouffard Peter S. Chines Pedro Cruz Nancy F. Hansen Jamie K. Teer Baishali Maskeri Alice C. Young NISC Comparative Sequencing Program Teri A. Manolio Alexander F. Wilson Toren Finkel Paul Hwang Andrew Arai Alan T. Remaley Vandana Sachdev Robert Shamburek Richard O. Cannon Eric D. Green 《Genome research》2009,19(9):1665-1674
ClinSeq is a pilot project to investigate the use of whole-genome sequencing as a tool for clinical research. By piloting the acquisition of large amounts of DNA sequence data from individual human subjects, we are fostering the development of hypothesis-generating approaches for performing research in genomic medicine, including the exploration of issues related to the genetic architecture of disease, implementation of genomic technology, informed consent, disclosure of genetic information, and archiving, analyzing, and displaying sequence data. In the initial phase of ClinSeq, we are enrolling roughly 1000 participants; the evaluation of each includes obtaining a detailed family and medical history, as well as a clinical evaluation. The participants are being consented broadly for research on many traits and for whole-genome sequencing. Initially, Sanger-based sequencing of 300–400 genes thought to be relevant to atherosclerosis is being performed, with the resulting data analyzed for rare, high-penetrance variants associated with specific clinical traits. The participants are also being consented to allow the contact of family members for additional studies of sequence variants to explore their potential association with specific phenotypes. Here, we present the general considerations in designing ClinSeq, preliminary results based on the generation of an initial 826 Mb of sequence data, the findings for several genes that serve as positive controls for the project, and our views about the potential implications of ClinSeq. The early experiences with ClinSeq illustrate how large-scale medical sequencing can be a practical, productive, and critical component of research in genomic medicine.Elucidating the sequence of the human genome (International Human Genome Sequencing Consortium 2001, 2004) and subsequent advances in DNA sequencing technologies (Mardis 2008) have the potential to dramatically improve the delivery of health care through the acquisition of genomic information about individual patients. However, much research will be needed to develop medical applications of genomics; for example, little is known about how to organize and implement large-scale medical sequencing (LSMS; i.e., systematic resequencing of human DNA) in a clinical context. Other approaches for applying high-throughput genomics to health care (e.g., assaying single-nucleotide polymorphisms and establishing gene-expression profiles) offer diagnostic promise; these are not further considered here, as our focus is on LSMS for studying the relationship of germline genomic variation to health and disease.We recently launched ClinSeq (http://genome.gov/20519355), a project that aims to apply LSMS within a clinical research environment to answer questions about the genetic basis of health, disease, and drug response. The application of genomic approaches (in particular LSMS) in a clinical research context is associated with a number of considerations that define key “dimensions” of any study: the number of subjects, the associated clinical data, and the breadth of genome covered (Fig. 1). Numerous detailed studies of single genes have been carried out; while often performed on many participants with significant amounts of phenotypic information, they are focused on a very small portion of the genome. The flurry of papers that describe recently generated whole-genome sequences (Levy et al. 2007; Bentley et al. 2008; Wang et al. 2008; Wheeler et al. 2008) has provided the first true individual genome sequences, including a modest amount of associated clinical data; however, the number of examples is small to date. Greater numbers are promised by the 1000 Genomes Project (http://www.1000genomes.org/), although no phenotypic information will be available for the individuals being studied. ClinSeq aims to model a more ideal study with respect to these three dimensions (Fig. 1), with the potential to further move toward the ultimate ideal as technology advances.Open in a separate windowFigure 1.A spatial conceptualization of research studies in genomic medicine. There are three key “dimensions” to consider when applying genomics to clinical research: genome breadth (the fraction of the genome that is interrogated), number of subjects or participants, and the associated clinical data about those individuals (including its depth, breadth, and rigor). While the ideal study would acquire whole-genome sequences from large numbers of extensively phenotyped subjects, this is currently impractical. Single-gene studies can involve a few or numerous subjects and extensive clinical data, but by definition involve the examination of only a single gene and thus occupy one wall of this space. The individual genomes that have recently been sequenced (Levy et al. 2007; Bentley et al. 2008; Wang et al. 2008; Wheeler et al. 2008) provide nearly complete genome breadth, but with limited clinical data; further, their limited subject numbers place them on another wall of this space. The 1000 Genomes Project (http://www.1000genomes.org/) is providing large subject numbers and extensive genome breadth, but no clinical data—positioning it on the floor of this space. ClinSeq aims to reside in the center of this space, having attributes of substantial subject size (n = 1000 initially), moderate genome breadth (∼400 genes initially, with plans for expanding this breadth), and substantial clinical data.The general aims of ClinSeq are to: (1) develop the infrastructure and approaches to acquire and analyze genome sequence from individual research participants; (2) pilot the use of LSMS to elucidate the genetic architecture underlying human traits; (3) provide an open, shared resource and environment for basic and clinical researchers to work collaboratively to perform research in genomic medicine; and (4) establish approaches for informed consent and the return of genetic information to subjects participating in LSMS studies. In pursuing these aims, our overriding goals include modeling whole-genome sequence acquisition in a manner that is practical for a clinical research setting, advancing our understanding of the genetic basis of important human diseases and traits, and establishing how to scale LSMS prior to the day when whole-genome sequencing becomes part of routine clinical practice. In this paper, we describe the ClinSeq study design, provide a snapshot of our very early data generation, and discuss the implications of this study for the nascent field of genomic medicine. 相似文献
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Ashish V. Joshi S. Suresh Madhavan Ambarish Ambegaonkar Michael Smith Virginia Scott Harakh Dedhia 《The Journal of asthma》2006,43(7):521-526
Objective. Examine the association of medication adherence with workplace productivity and health-related quality of life (HRQL) in asthma patients. Methods. Adult patients with asthma in a state health insurance program identified from medical claims (July 2001-June 2003) were mailed a three-part survey to measure HRQL (St. George's Respiratory Questionnaire), workplace productivity (Workplace Productivity Short Inventory), and self-reported medication adherence (Morisky Scale). Results. The symptoms domain had the worst HRQL scores, followed by the activity and impacts domains; 39% of the participants reported themselves as “high” adherent, whereas 19% were “medium,” and 42% were “low” adherent. Asthma resulted in productivity losses of $597 ± $1,024 (absenteeism) and $658 ± $1,808 (presenteeism) per enrollee per year. Conclusions. Asthma was associated with HRQL detriments and workplace productivity losses. 相似文献
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Kamalesh Sarkar Baishali Bal Rita Mukherjee Sekhar Chakraborty Swapan Kumar Niyogi Malay Kumar Saha 《Substance use & misuse》2013,48(3):341-352
A study was conducted in June 2004 to find out the epidemiology of HIV infection among injecting drug users (IDUs) of Darjeeling District of West Bengal, eastern India. The district headquarter, Darjeeling town, also known as “Queen of Hills,” is a beautiful spot situated in Himalayan West Bengal that attracts a large number of tourists each year from all over the world. Another unique feature of the district is that it has international boundaries with three countries, Nepal, Bhutan, and Bangladesh. Siliguri, the part of the district on plains, acts as a transit station for these countries as well as to the entire Himalayan region of West Bengal and neighboring state, Sikkim. It is also a transit point to all northeastern states of India: Assam, Arunachal Pradesh, Nagaland, Manipur, Mizoram, Meghalaya, and Tripura. Two hundred twenty-eight study subjects (IDUs) were included in this community-based cross-sectional study from all four subdivisions of the district. Informed consent was obtained, and then personal interviews, followed by blood testing were performed using unlinked anonymous procedure. The study revealed that overall HIV seroprevalence among IDUs was 11.8% (n = 27; 95% confidence interval, 7.9–16.7), whereas seroprevalence of hepatitis C was found to be 47.7% (n = 97). Prevalence of HIV was higher in subjects from hill districts (13.5%) compared with subjects from the plains (9.2%). It also revealed that most IDUs (75.3%) used “brown sugar,” an impure form of heroin, as their major addictive substance followed by injection norphine. Sharing of injecting equipment was found to be as high as 67% among IDUs, and sharing of drugs from common ampules was found to be 35.5% of the studied subjects (n = 93). Most subjects (96%) were found to clean their injecting paraphernalia with plain water. Most IDUs (98%) were found to inject intravenously. About 52% of IDUs visited sex workers one or more times within the last 1 year, and 15% of the interviewed subjects (n = 93) reported to suffer from sexually transmitted diseases during the same period. All the IDUs knew about HIV/AIDS. About 69% of the subjects knew that apparently healthy looking person might have HIV infection. HIV was found to be associated significantly with age of the injectors and duration of injecting practices. The study revealed the epidemic of HIV and hepatitis C among IDU populations at this bordering district of West Bengal for the first time that requires urgent intervention at local, national, and international levels. 相似文献
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Guillain-Barre syndrome (GBS) is a rare acute paralytic polyneuropathy, with an incidence of about 1 in 100,000. It occurs in adults and children. It is an autoimmune disorder of the peripheral nervous system often triggered by acute infections – the most common being gastrointestinal or respiratory – leading to an immune mediated response of producing antibodies to antigens which react with the myelin sheath of the peripheral nerves, resulting in demyelination and/or axonal injury. In severe cases, GBS may lead to respiratory failure, and even death. Current treatment options include treatment with intravenous immunoglobulin and/or plasmapharesis which are aimed at neutralising, and removal of circulating antibodies from the bloodstream respectively, alongside supportive measures to maintain motor function. 相似文献
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Analysis of Episodes of Care in Medicare Beneficiaries Newly Diagnosed with Alzheimer's Disease 下载免费PDF全文