tbuckley/cabot-search huggingface dataset:
The Promise and Challenges of Next-Generation Genome Sequencing for Clinical Care
Authors: Katherine A. Johansen Taber, Barry D. Dickinson, Modena Wilson
Journal: JAMA Internal Medicine (2013)

With increased speed and decreased costs, next-generation gene sequencing has the potential to improve medical care by making possible widespread evaluation of patients' genomes in clinical settings. The entire genome of an individual can now be sequenced in less than 1 week at a cost of $5000 to $10,000; the cost will continue to decline. Analyses based on next-generation sequencing include whole-genome sequencing and whole-exome sequencing; DNA sequences that encode proteins are collectively known as the exome. In some instances, whole genome and whole-exome sequencing have already helped to accurately diagnose diseases with atypical manifestations, that are difficult to diagnose using clinical or laboratory criteria alone, or that otherwise require extensive or costly evaluation. For some patients with malignant neoplasms, next-generating sequencing can improve tumor classification, diagnosis, and management. Many challenges remain, however, such as the storage and interpretation of vast amounts of sequence data, training physicians and other health care professionals whose knowledge of genetics may be insufficient, effective genetic counseling and communication of results to patients, and establishing standards for the appropriate use of the technology. Rigorous studies are needed to assess the utility of whole-genome and whole-exome sequencing in large groups of patients, including comparative studies with other approaches to screening and diagnosis, and the evaluation of clinical end points and health care costs. The successes to date have been in single cases or in very small groups of patients. At present, although whole-genome or whole-exome sequencing show great promise, they should be incorporated into patient care only in limited clinical situations.
Breast Cancer Screening: A Summary of the Evidence for the U.S. Preventive Services Task Force
Authors: Linda L. Humphrey
Journal: Annals of Internal Medicine (2002)

Purpose: To synthesize new data on breast cancer screening for the U.S. Preventive Services Task Force. Data Sources: MEDLINE; the Cochrane Controlled Trials Registry; and reference lists of reviews, editorials, and original studies. Study Selection: Eight randomized, controlled trials of mammography and 2 trials evaluating breast self-examination were included. One hundred fifty-four publications of the results of these trials, as well as selected articles about the test characteristics and harms associated with screening, were examined. Data Extraction: Predefined criteria were used to assess the quality of each study. Meta-analyses using a Bayesian random-effects model were conducted to provide summary relative risk estimates and credible intervals (CrIs) for the effectiveness of screening with mammography in reducing death from breast cancer. Data Synthesis: For studies of fair quality or better, the summary relative risk was 0.84 (95% CrI, 0.77 to 0.91) and the number needed to screen to prevent one death from breast cancer after approximately 14 years of observation was 1224 (CrI, 665 to 2564). Among women younger than 50 years of age, the summary relative risk associated with mammography was 0.85 (CrI, 0.73 to 0.99) and the number needed to screen to prevent one death from breast cancer after 14 years of observation was 1792 (CrI, 764 to 10 540). For clinical breast examination and breast self-examination, evidence from randomized trials is inconclusive. Conclusions: In the randomized, controlled trials, mammography reduced breast cancer mortality rates among women 40 to 74 years of age. Greater absolute risk reduction was seen among older women. Because these results incorporate several rounds of screening, the actual number of mammograms needed to prevent one death from breast cancer is higher. In addition, each screening has associated risks and costs.
Standardised nomenclature for glucocorticoid dosages and glucocorticoid treatment regimens: current questions and tentative answers in rheumatology
Authors: F Buttgereit
Journal: Annals of the Rheumatic Diseases (2002)

In rheumatology and other medical specialties there is a discrepancy between the widespread use and the imprecise designation of glucocorticoid treatment regimens. Verbal descriptions of glucocorticoid treatment regimens used in various phases of diseases vary between countries and institutions. Given this background, a workshop under the auspices of the EULAR Standing Committee on International Clinical Studies including Therapeutic Trials was held to discuss this issue and to seek a consensus on nomenclature for glucocorticoid treatment. This report summarises the panel9s discussion and recognises that answers derived from consensus conferences are not definitive. Nevertheless, recommendations on glucocorticoid treatment are presented that (1) reflect current and best knowledge available and (2) take into account current clinical practice. A question-answer rationale presentation style has been chosen to convey the messages, to summarise the meeting in a readable format, and to avoid dogmatism.
Merlin/NF2 Loss-Driven Tumorigenesis Linked to CRL4DCAF1-Mediated Inhibition of the Hippo Pathway Kinases Lats1 and 2 in the Nucleus
Authors: Wei Li, Jonathan Cooper, Lu Zhou, Chenyi Yang, Hediye Erdjument-Bromage, David Zagzag, Matija Snuderl, Marc Ladanyi, C. Oliver Hanemann, Pengbo Zhou, Matthias A. Karajannis, Filippo G. Giancotti
Journal: Cancer Cell (2014)
Mechanisms of quinidine-induced depression of maximum upstroke velocity in ovine cardiac Purkinje fibers.
Authors: F M Weld, J Coromilas, J N Rottman, J T Bigger
Journal: Circulation Research (1982)

A major advance in understanding how quinidine depresses maximum upstroke velocity (Vmax) is the Hondeghem-Katzung mathematical model which incorporates voltage-independent rate constants for binding to and unbinding from resting, open, and inactive Na channels, and a voltage shift of -40 mV for the Hodgkin-Huxley h-kinetics of quinidine-associated Na channels. Using a double microelectrode voltage clamp technique to control transmembrane voltage and apply conditioning pulses, we found that quinidine blockade increased as transmembrane voltage became more positive in the range -60 to +40 mV, and that the rate of quinidine dissociation increased as transmembrane voltage became more negative in the range -60 to -140 mV. The relationship of Vmax to transmembrane voltage obtained at drive cycles from 500 msec to 20 seconds conformed to the model modified to include voltage-dependent rate constants without the postulated -40-mV shift for quinidine-associated channels. Thus binding of quinidine to inactive Na channels and unbinding from resting channels are both voltage-dependent and can explain frequency and voltage dependent actions of quinidine on Vmax without any voltage shift for quinidine-associated channels.
Lesson of the week: Hypothyroidism mimicking intra-abdominal malignancy
Authors: S T M Krishnan
Journal: BMJ (2002)

Thyroid function should be checked in all patients with ascites and raised CA 125 concentrations 

Primary hypothyroidism is a relatively common endocrine disorder. Because awareness is now high and screening is easy, the condition is detected early in most patients, when symptoms and signs are mild or often non-specific. Patients with more severe hypothyroidism may present with clinical features such as coma, cerebellar ataxia, pericardial effusion, and ascites. These features mimic those of other conditions, and as severe hypothyroidism is uncommon, the condition can be overlooked. We present a case in which the clinical presentation supported by a raised CA 125 concentration led to an incorrect presumptive diagnosis of ovarian malignancy.

A 74 year old woman presented with increasing abdominal swelling over four months, along with exertional dyspnoea, lethargy, and anorexia. She had been referred by her general practitioner for an urgent surgical outpatient appointment with a provisional diagnosis of intra-abdominal malignancy. However, before her appointment she was admitted as a medical emergency because of worsening breathlessness. She gave no history of thyroid dysfunction, neck surgery, irradiation, or heart disease and was taking no drugs.

On examination she appeared cachectic and pale. She had vitiligo but no lymphadenopathy, signs of chronic liver disease, or goitre. She spoke with a hoarse voice. Her temperature was 36.5½C, pulse 70 beats/min, and blood pressure 140/80 mm Hg. The jugular venous pressure was not raised. She had moderate …
Plasma secretory leukocyte protease inhibitor in febrile patients; An indicator of the presence and extent of pulmonary infection
Authors: L.A. Duits, G.S. Tjabringa, N.J.M. Aarts, J.W. van't Wout, P.S. Hiemstra, P.H. Nibbering and, J.T. van Dissel
Journal: Clinical Microbiology and Infection (2003)
Out-of-Hospital CPR
Authors: B. Tilman Jolly
Journal: JAMA (1994)

<h3>To the Editor.</h3> —As an emergency physician, I read with great interest the recent articles by Kellermann et al,<sup>1</sup>Bonnin et al,<sup>2</sup>and the accompanying Editorial by Gray.<sup>3</sup>The authors address an area that will take on added importance as the attention of the nation turns to health system reform with its apparent emphasis on global cost containment. However, a major area of practical importance has not been addressed by the authors. A death in the emergency department involves more than just physiological determinations of viability. Perhaps a majority of eventual outcomes are obvious on initial presentation of the patient. What happens after the death is a much more difficult subject to study. Sociological realities of our nation typically demand that some authority, usually a physician, preside over the ritual of death. In the simplest terms, the authority must tell the family and friends what has happened,
Edematous Erythema, Subcutaneous Plaques, and Severe Pain in the Lower Extremities in an Immunocompromised Patient
Authors: Ying-Guo Ding, Hong Fang
Journal: JAMA (2013)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
The venous thrombotic risk of oral contraceptives, effects of oestrogen dose and progestogen type: results of the MEGA case-control study
Authors: A van Hylckama Vlieg, F M Helmerhorst, J P Vandenbroucke, C J M Doggen, F R Rosendaal
Journal: BMJ (2009)

<b>Objective</b> To assess the thrombotic risk associated with oral contraceptive use with a focus on dose of oestrogen and type of progestogen of oral contraceptives available in the Netherlands. <b>Design</b> Population based case-control study. <b>Setting</b> Six participating anticoagulation clinics in the Netherlands (Amersfoort, Amsterdam, The Hague, Leiden, Rotterdam, and Utrecht). <b>Participants</b> Premenopausal women &lt;50 years old who were not pregnant, not within four weeks postpartum, and not using a hormone excreting intrauterine device or depot contraceptive. Analysis included 1524 patients and 1760 controls. <b>Main outcome measures</b> First objectively diagnosed episodes of deep venous thrombosis of the leg or pulmonary embolism. Odds ratios calculated by cross-tabulation with a 95% confidence interval according to Woolf’s method; adjusted odds ratios estimated by unconditional logistic regression, standard errors derived from the model. <b>Results</b> Currently available oral contraceptives increased the risk of venous thrombosis fivefold compared with non-use (odds ratio 5.0, 95% CI 4.2 to 5.8). The risk clearly differed by type of progestogen and dose of oestrogen. The use of oral contraceptives containing levonorgestrel was associated with an almost fourfold increased risk of venous thrombosis (odds ratio 3.6, 2.9 to 4.6) relative to non-users, whereas the risk of venous thrombosis compared with non-use was increased 5.6-fold for gestodene (5.6, 3.7 to 8.4), 7.3-fold for desogestrel (7.3, 5.3 to 10.0), 6.8-fold for cyproterone acetate (6.8, 4.7 to 10.0), and 6.3-fold for drospirenone (6.3, 2.9 to 13.7). The risk of venous thrombosis was positively associated with oestrogen dose. We confirmed a high risk of venous thrombosis during the first months of oral contraceptive use irrespective of the type of oral contraceptives. <b>Conclusions</b> Currently available oral contraceptives still have a major impact on thrombosis occurrence and many women do not use the safest brands with regard to risk of venous thrombosis.
Natural, genetically determined resistance toward influenza virus in hemopoietic mouse chimeras. Role of mononuclear phagocytes.
Authors: O Haller, H Arnheiter, J Lindenmann
Journal: The Journal of Experimental Medicine (1979)

Radiation chimeras produced by crosswise transfers of bone-marrow cell among histocompatible mice susceptible, or genetically resistant, to lethal challenge by a number of myxoviruses were used to test whether macrophage resistance (as assessed in vitro) and resistance of the animal (as measured in vivo), both previously shown to be brought about by the gene Mx, were causally related. 49 chimeras were tested individually, both of resistance of their macrophages to in vitro challenge with M-TUR (a strain of avian influenza virus A/Turkey/England/63 adapted to grow in cultured mouse peritoneal macrophages), and for resistance of the animal in vivo upon challenge with pneumotropic, neurotropic, or hepatotropic influenza viruses. Cultivated Kupffer cells and peritoneal macrophages harvested from chimeric mice expressed the resistance phenotype of the bone-marrow donor irrespective of the host environment in which they had differentiated. However, susceptibility or resistance in vivo was according to the genotype of the host. Thus, inborn resistance of radiation chimeras was found to be independent of Mx-gene expression in cells of the hemopoietic system.
The cell surface molecule recognized by the erythrocyte receptor of T lymphocytes. Identification and partial characterization using a monoclonal antibody.
Authors: T Hünig
Journal: The Journal of Experimental Medicine (1985)

A monoclonal antibody (mAb) to sheep red blood cells (SRBC), termed L180/1, is described that completely blocks rosette formation between SRBC and human or sheep T lymphocytes. L180/1 precipitated a minor glycoprotein of about approximately 42,000 mol wt from surface-labeled SRBC. This glycoprotein was partially affinity purified and found to block E rosette formation and to compete with anti-T11 mAb for the E receptor. The molecule detected by mAb L180/1 thus appears to be recognized by the E receptor and was given the preliminary name, T11 target structure (T11TS). Since the mAb to sheep T11TS blocks the binding of SRBC to both human and sheep T cells, and mAb to T11 blocks the binding of red cells from human and sheep to the human E receptor, we concluded that analogous receptor-ligand (T11-T11TS) systems exist in man and sheep that are crossreactive over the species barrier. The possibility is discussed that the E receptor, which is known to be involved in T cell activation, and T11TS function as complementary cell interaction molecules in T cell responses.
Isolation and functional properties of murine hematopoietic stem cells that are replicating in vivo.
Authors: M A Goodell, K Brose, G Paradis, A S Conner, R C Mulligan
Journal: The Journal of Experimental Medicine (1996)

Hematopoietic stem cells (HSC) are multipotent cells that reside in the bone marrow and replenish all adult hematopoietic lineages throughout the lifetime of the animal. While experimenting with staining of murine bone marrow cells with the vital dye, Hoechst 33342, we discovered that display of Hoechst fluorescence simultaneously at two emission wavelengths revealed a small and distinct subset of whole bone marrow cells that had phenotypic markers of multipotential HSC. These cells were shown in competitive repopulation experiments to contain the vast majority of HSC activity from murine bone marrow and to be enriched at least 1,000-fold for in vivo reconstitution activity. Further, these Hoechst-stained side population (SP) cells were shown to protect recipients from lethal irradiation at low cell doses, and to contribute to both lymphoid and myeloid lineages. The formation of the Hoechst SP profile was blocked when staining was performed in the presence of verapamil, indicating that the distinctly low staining pattern of the SP cells is due to a multidrug resistance protein (mdr) or mdr-like mediated efflux of the dye from HSC. The ability to block the Hoechst efflux activity also allowed us to use Hoechst to determine the DNA content of the SP cells. Between 1 and 3% of the HSC were shown to be in S-G2M. This also enabled the purification of the G0-G1 and S-G2M HSC had a reconstitution capacity equivalent to quiescent stem cells. These findings have implications for models of hematopoietic cell development and for the development of genetic therapies for diseases involving hematopoietic cells.
The safety of IPI-926, a novel hedgehog pathway inhibitor, in combination with gemcitabine in patients (pts) with metastatic pancreatic cancer.
Authors: J. Stephenson, D. A. Richards, B. M. Wolpin, C. Becerra, J. T. Hamm, W. A. Messersmith, S. Devens, J. Cushing, J. Goddard, T. Schmalbach, C. S. Fuchs
Journal: Journal of Clinical Oncology (2011)

4114 Background: IPI-926 is a novel, selective, oral, natural product-derived small molecule that targets the Hedgehog (Hh) pathway by inhibiting Smoothened (Smo). Inhibition of Smo can repress malignant activation of the Hh pathway, resulting in decreased desmoplasia and improved delivery of chemotherapy to pancreatic tumors. Methods: A phase Ib/II trial is underway to evaluate the safety profile and efficacy of IPI-926 in combination with gemcitabine. Eligible pts with previously untreated metastatic pancreatic cancer and ECOG performance status 0-1 had IPI-926 administered orally daily (QD) for a 28-day cycle, in 3 to 6 pt cohorts. IV gemcitabine (1,000 mg/m2) was administered once weekly for 3 weeks followed by 1 week off. DLTs were evaluated during Cycle 1. Results: As of Dec 2010, 15 pts with a median age of 67 years (range 58-83) have been enrolled in the phase Ib portion of this trial at dose levels of IPI-926 ranging from 110-160 mg QD, and a median of 3 cycles completed (1-6). No Grade 4/ 5 adverse events (AE) have been observed related to either study drug, and no IPI-926-related serious AEs have been noted. The most common IPI-926-related AEs observed include fatigue (40% total, 0% Grade 3), nausea (40%, 0%), ALT increased (13%, 7%), AST increased (13%, 7%), anemia (13%, 0%), and vomiting (13%, 0%). The observed safety profile for gemcitabine has been consistent with published data. The one DLT observed to date (130 mg of IPI-926) was Grade 3 AST increase, which was asymptomatic, resolved with dose interruption, and did not recur after dose reduction. No apparent drug interaction between IPI-926 and gemcitabine has been observed to date. Preliminary data include 3 radiographic partial responses in the 9 pts with post-baseline scans. Conclusions: IPI-926 in combination with gemcitabine has been well tolerated to date in patients with metastatic pancreatic cancer, without unexpected toxicity, and preliminary evidence of clinical activity has been observed. The phase Ib portion of this trial is now fully enrolled with ongoing pt treatment and data collection. Clinical evaluation of this combination continues in a randomized, double blind, placebo controlled phase II trial.
Multicenter Study of Human Immunodeficiency Virus–Related Germ Cell Tumors
Authors: T. Powles, M. Bower, G. Daugaard, J. Shamash, A. De Ruiter, M. Johnson, M. Fisher, J. Anderson, S. Mandalia, J. Stebbing, M. Nelson, B. Gazzard, T. Oliver
Journal: Journal of Clinical Oncology (2003)

Testicular germ cell tumors (GCT) occur at increased frequency in men with human immunodeficiency virus (HIV). This multicenter study addresses the characteristics of these tumors.Patients with HIV-related GCT were identified from six HIV treatment centers. The incidence was calculated from the center with the most complete linked oncology and HIV databases.Thirty-five patients with HIV-related GCT were identified. The median age at GCT diagnosis was 34 years (range, 27 to 64 years). The median CD4 cell count was 315/mm3 (range, 90 to 960/mm3) at this time. The histologic classification was seminoma in 26 patients (74%) and nonseminomatous GCT in nine patients (26%). Twenty-one patients (60%) had stage I disease and 14 patients had metastatic disease. Overall six patients relapsed, three died from GCT, and seven died from HIV disease, resulting in a 2-year overall survival rate of 81%. HIV-related seminoma occurred more frequently than in the age- and sex-matched HIV-negative population, with a relative risk of 5.4 (95% confidence interval, 3.35 to 8.10); however, nonseminomatous GCT did not occur more frequently, and there was no change in the incidence of GCT since the introduction of highly active antiretroviral therapy.Testicular seminoma occurs significantly more frequently in HIV-positive men than in the matched control population. Patients with HIV-related GCTs present and should be treated in a similar manner to those in the HIV-negative population. After a median follow-up of 4.6 years, 9% of the patients died from GCT. Most of the mortality relates to HIV infection.