tbuckley/cabot-search huggingface dataset:
The Uracil Breath Test in the Assessment of Dihydropyrimidine Dehydrogenase Activity: Pharmacokinetic Relationship between Expired 13CO2 and Plasma [2-13C]Dihydrouracil
Authors: Lori K. Mattison, Jeanne Fourie, Yukihiro Hirao, Toshihisa Koga, Renee A. Desmond, Jennifer R. King, Takefumi Shimizu, Robert B. Diasio
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Dihydropyrimidine dehydrogenase (DPD) deficiency is critical in the predisposition to 5-fluorouracil dose-related toxicity. We recently characterized the phenotypic [2-13C]uracil breath test (UraBT) with 96% specificity and 100% sensitivity for identification of DPD deficiency. In the present study, we characterize the relationships among UraBT-associated breath 13CO2 metabolite formation, plasma [2-13C]dihydrouracil formation, [2-13C]uracil clearance, and DPD activity. Experimental Design: An aqueous solution of [2-13C]uracil (6 mg/kg) was orally administered to 23 healthy volunteers and 8 cancer patients. Subsequently, breath 13CO2 concentrations and plasma [2-13C]dihydrouracil and [2-13C]uracil concentrations were determined over 180 minutes using IR spectroscopy and liquid chromatography-tandem mass spectrometry, respectively. Pharmacokinetic variables were determined using noncompartmental methods. Peripheral blood mononuclear cell (PBMC) DPD activity was measured using the DPD radioassay. Results: The UraBT identified 19 subjects with normal activity, 11 subjects with partial DPD deficiency, and 1 subject with profound DPD deficiency with PBMC DPD activity within the corresponding previously established ranges. UraBT breath 13CO2 DOB50 significantly correlated with PBMC DPD activity (rp = 0.78), plasma [2-13C]uracil area under the curve (rp = −0.73), [2-13C]dihydrouracil appearance rate (rp = 0.76), and proportion of [2-13C]uracil metabolized to [2-13C]dihydrouracil (rp = 0.77; all Ps &amp;lt; 0.05). Conclusions: UraBT breath 13CO2 pharmacokinetics parallel plasma [2-13C]uracil and [2-13C]dihydrouracil pharmacokinetics and are an accurate measure of interindividual variation in DPD activity. These pharmacokinetic data further support the future use of the UraBT as a screening test to identify DPD deficiency before 5-fluorouracil-based therapy.
Cisplatinum Sensitivity of BRCA1-Mutated HCC1937 Breast Cancer Cells Is Linked to Impairment of Notch Signaling and Is Increased by γ-Secretase Inhibitors.
Authors: M. Ventura, M. Di Martino, M. Arbitrio, M. Propato, G. Perri, A. Bulotta, T. Calimeri, M. Pacicca, P. Tassone, P. Tagliaferri
Journal: Cancer Research (2009)

Abstract BRCA1 plays a critical role in DNA-damage repair mechanisms elicited by cell exposure to anti-tumor agents. HCC1937 is a BRCA1-defective breast cancer cell line which discloses higher sensitivity to cisplatinum (CDDP) as compared to the BRCA1 full-length cDNA transfected clone, HCC1937/wtBRCA1. By cDNA microarray whole gene expression profile and Ingenuity Pathway Analysis (IPA) software, we found a differential modulation of Notch signaling after CDDP exposure in HCC1937 cell line as compared to BRCA1-reconstituted clone with a strong down-regulation of Notch1, 2 and 3 expression together with other genes involved in the Notch signaling network, including Hes1 and Jag1. Notch pathway was not affected by CDDP exposure in BRCA1-reconstituted cells. By Western Blot analysis, we next analyzed if the different trascriptional response of the two cell lines to CDDP occurred together with down-regulation of Notch protein in BRCA1-defective cells. We found enhanced expression of BRCA1 in BRCA1-transfected cells. We then analyzed the Notch 3 protein's expression in HCC1937 and HCC1937/wtBRCA1. By Western blot analysis, we demonstrated a significant reduction of Notch 3 protein's expression following CDDP exposure at the IC50 dose for 12, 18 and 24 hours, in HCC1937 as compared to HCC1937/wtBRCA1, consistently with gene expression results. In the aim of evaluating the role of Notch signaling in the regulation of the pharmacological response to CDDP in BRCA1-defective cells, we exposed HCC1937 cells to the pan-Notch inhibitor, γ-secretase inhibitor XII (GSI-XII), alone or in combination with CDDP, and we elvaluated, by MTT assay, in vitro growth effects on cell survival. We observed a time and dose dependent decrease of cell growth of HCC1937 following GSI-XII exposure as compared to BRCA1-reconstituted clone, with an IC50 between 25 and 35 microM as single agent, while HCC1937/wtBRCA1 where highly resistant to the drug. The combination of GSI-XII plus CDDP produced a significant sinergistic antitumor effect at 48 hours in HCC1937 which did not occurred in HCC1937/wtBRCA1. Our findings suggest that the high sensitivity of BRCA1-defective cells to CDDP exposure may be related not only to depression of the DNA-damage repair machinery but also to down-modulation of the Notch survival pathway. Moreover, our data indicate that the antitumor activity of CDDP is enhanced by combination with the Notch inhibitor GSI-XII suggesting that γ-secretase inhibitors may represent a potential and novel therapeutic tool in this specific setting. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 3128.
Preliminary Observations on the Effect of Recombinant Leukocyte a Interferon in Homosexual Men with Kaposi's Sarcoma
Authors: Susan E. Krown, Francisco X. Real, Susanna Cunningham-Rundles, Patricia L. Myskowski, Benjamin Koziner, Seymour Fein, Abraham Mittelman, Herbert F. Oettgen, Bijan Safai
Journal: New England Journal of Medicine (1983)

Preliminary clinical trials have shown that both natural and recombinant-DNA-produced human interferons are occasionally capable of inhibiting the growth of some tumors.1 2 3 4 Although the tumors responding to interferon have most often been those without evidence for a viral association, case reports have appeared of therapeutic effects in patients with nasopharyngeal carcinoma,5 for which there is strong serologic evidence supporting a viral association, and in patients with laryngeal papilloma,6 for which the available evidence supports a viral pathogenesis. Interferons have also been shown to modify the course of chronic viral infections in human beings, including infections induced by hepatitis B virus . . .
Carbohydrate Recognition by <i>Mycoplasma pneumoniae</i> and Pathologic Consequences
Authors: Ten Feizi, R. Wendy Loveless
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

Mycoplasma pneumoniae infection in the human is often followed by a transient autoimmune hemolytic disorder characterized by high titer autoantibodies to a carbohydrate antigen, the I antigen. Because the major host cell receptor for the Mycoplasma is the sialylated form of this antigen, it is likely that the immunologic disorder is initiated by the microbe-saccharide interaction. Here we review briefly knowledge on the autoantibodies and the structures and distribution of the saccharide antigens and receptors. We discuss possible mechanisms for the triggering of autoantibody production and consider ways in which perturbation of various glycoprotein carriers of the carbohydrate ligands may elicit a variety of pathobiologic responses. We conclude by highlighting ideas on further molecular dissections of the elements of the microbe-host interaction.
Sump syndrome and biliary adenocarcinoma 40 years after surgical choledochoduodenal fistula
Authors: I. Mecklenburg, R. Scheubel, H. Messmann
Journal: Endoscopy (2007)

A 74-year-old icteric female presented with abdominal cramps, chills, and night sweats, and reported a 20-lb weight loss since the symptoms started 3 months previously. Past medical history included cholecystectomy, which was performed in 1965 due to gallbladder stones; the patient had been asymptomatic for the past 40 years.
Emergency Department Diagnosis and Management of Skin Diseases With Real-Time Teledermatologic Expertise
Authors: Tu Anh Duong, Florence Cordoliani, Caroline Julliard, Emmanuelle Bourrat, Stephanie Regnier, Loïc de Pontual, Christophe Leroy, Sébastien Gallula, Caroline Aparicio, Nicolas Legendre, Martine Bagot, Fabien Guibal
Journal: JAMA Dermatology (2014)

Skin conditions are a common reason for patients to consult emergency department (ED) physicians.To evaluate real-time teledermatologic expertise with the use of mobile telephones for the diagnosis and management of skin conditions in patients seen in the ED.This observational study of adults who consecutively consulted in the ED for a dermatologic condition was conducted under routine conditions in the ED from May 1, 2008, through June 30, 2010.Diagnosis agreement and management concordance.One hundred eleven patients were enrolled in the study. Eighty-three patients (74.8%) were evaluated using videoconferencing. Dermatologic remote expertise invalidated, enlarged, or clarified ED physicians' diagnosis and management in 75 of 110 cases (68.2%). Videoconferencing improved the diagnostic performance in 57 of 83 cases (68.7%) (P < 10(-4)). Management concordance was moderate between ED physicians and dermatologists for specialist consultation within 24 hours (κ, 0.49; 95% CI, 0.14-0.84) and immediate hospitalization (κ, 0.49; 95% CI, 0.41-0.57). Patients were significantly more often discharged by dermatologists (46.8% vs 39.1%) (P < 10(-4)).Compared with standard hardware, new-generation mobile devices reduce the cost of videoconferencing, increase the versatility of teledermatology, and decrease general practitioner investment time.
Congenital Heart Disease and Other Malformations Produced by Influenza A Virus and Allantoic Fluid in the Chick Embryo
Authors: Maria V. de la Cruz, Carlos Campillo-Sainz, Simón Munoz-Armas, Asunción Pascual-Chávez, Rafaela Zamudio-Bandera
Journal: Circulation Research (1963)

The effect of both active and heat-inactivated influenza A virus, chick allantoic fluid, and of buffered saline solution on the mortality and appearance of congenital malformations in the white Leghorn chick embryo, especially in the heart, was studied. Active influenza A virus produced a high mortality rate during the initial stages of development, when formation of the cardiac septa had barely begun and the primordia of the valves were yet to appear. Consequently, no congenital heart disease was found in the group inoculated with active virus, though profound alterations of the nervous system, sensorial organs and general body shape were observed. The effects of allantoic fluid with and without heat-inactivated virus were the same high incidence of congenital valvular disease (pulmonary stenosis, thickening of the mitral valve), and interventricular septal defect. Inoculation of buffered saline solution produced an increased mortality rate and structural malformations outside the heart, but had no effect on the development of the heart. Possible mechanisms of action of these terato-genic agents are discussed.
Plasma leptin concentrations in Pima Indians living in drastically different environments.
Authors: C Fox, J Esparza, M Nicolson, P H Bennett, L O Schulz, M E Valencia, E Ravussin
Journal: Diabetes Care (1999)

OBJECTIVE: Plasma leptin, an important signal for the regulation of energy stores, is known to be influenced by many hormonal factors, but may also be affected by behavioral and environmental factors. The purpose of this study was to investigate the impact of lifestyle (diet composition, level of physical activity) on plasma leptin concentrations among Pima Indians living in drastically different environments. RESEARCH DESIGN AND METHODS: We studied 224 Mexican Pima Indians (115 women, 109 men) living a traditional lifestyle in a remote, mountainous area of northwest Mexico and 418 U.S. Pima Indians (281 women, 137 men) living a North American lifestyle on the Gila River Indian Reservation in Arizona. We hypothesized that the absolute value of leptin would be lower in Mexican Pima Indians because of their lower percent body fat, but could be further influenced by their lifestyle, independent of body composition. RESULTS: Leptin concentration (enzyme-linked immunosorbent assay [ELISA]) was strongly correlated with percent fat (bioimpedance) in Mexican Pima Indians (r = 0.83, P &amp;lt; 0.0001) and U.S. Pima Indians (r = 0.86, P &amp;lt; 0.0001). Among U.S. Pima Indians, independent of percent fat, subjects with type 2 diabetes had lower leptin than nondiabetic subjects (difference = 6.9 +/- 1.0 ng/ml, P &amp;lt; 0.002). Among nondiabetic subjects, Mexican Pima Indians had lower absolute leptin concentrations than U.S. Pima Indians, but higher after adjustment for percent body fat, waist circumference, age, and sex. In a subset of 70 pairs of subjects matched for sex and percent body fat, leptin concentration was 4.4 +/- 1.0 ng/ml (P &amp;lt; 0.0001) higher in Mexican Pima Indians versus U.S. Pima Indians. CONCLUSIONS: These results suggest that independent of body composition, leptin concentration may be increased by environmental factors, such as a high-carbohydrate diet and a high level of physical activity.
POSSIBLE HAZARD IN USE OF OILED SILK BIB
Authors: Curtis M. Galt
Journal: JAMA (1941)

<h3>To the Editor:—</h3> Believing that the oiled silk baby bib presents a real hazard, I submit the following report: Susan Fuller, aged 6 months, in perfect health, was lying awake in her bed, wearing an oiled silk bib. Something prompted the mother to go upstairs to take her a toy and she found the wet bib draped over the baby's face plastered against the mouth and nostrils. Respirations had ceased and the baby was apparently dead; she was rushed across the street to my office and found to be limp, her hands were cyanotic, her face and forehead were blotchy and there was bloody froth drooling from the nostrils and mouth. Artificial respiration succeeded in reviving her; except for a few spells of coughing up mucus, her recovery was uneventful and complete. It is suggested that, if this type of bib is used, it should be pinned to the shirt.
Islet Cell Tumors: Current Concepts and Management
Authors: PHILIP S. SCHEIN
Journal: Annals of Internal Medicine (1973)

The pancreatic islet is composed of three types of cells of neural crest origin, each with distinct histochemical and electromicroscopic features. Each type of cell may give rise to a benign or malignant neoplasm that usually presents with a clinical syndrome related to hypersecretion of a native or ectopic hormonal product. Diagnosis of the tumor depends most on specific assay of the hormone produced. In malignant insulinoma and Zollinger-Ellison syndrome an increase in plasma proinsulin-like component, or "big" gastrin, may be the most specific finding. The exact hormone responsible for the "pancreatic cholera" syndrome remains unknown, but biologically it is secretin-like. Treatment of the Zollinger-Ellison syndrome is removal of the end organ; direct resection of tumor is the primary form of therapy for all other islet cell neoplasms. Palliation of functioning malignancies often requires both antihormonal and anticancer chemotherapy. The use of streptozotocin and L-asparaginase to treat malignant insulinoma is reviewed.
Magnetic resonance imaging in patients with congenital heart disease.
Authors: C B Higgins, B F Byrd, D W Farmer, L Osaki, N H Silverman, M D Cheitlin
Journal: Circulation (1984)

Magnetic resonance imaging (MRI) was conducted with use of the spin-echo technique (0.35 Tesla) in 22 patients with a variety of congenital and cardiovascular anomalies and in 16 normal volunteers. Electrocardiographic (ECG) synchronization of the data acquisition produced transverse, parasagittal, and coronal tomograms that were used to define size and relationship of the great vessels and internal cardiac structures. MRI findings were corroborated by angiography and sector-scan echocardiography. In most patients the diagnosis had been established before the MRI study. MRI detected all of 11 abnormalities at the level of the great vessels, all of six atrial septal abnormalities, and 10 of 11 ventricular septal defects. Images of poor quality resulting from patient motion were obtained in the one instance in which a small ventricular septal defect was not imaged. Of two patients with Ebstein's anomaly, the displacement of the tricuspid leaflets was shown in one patient but was not evident in another. Complex anomalies such as double-outlet right ventricle, uncorrected L-transposition, single atrioventricular valve, single ventricle, and common ventricle were clearly shown by MRI. Initial experience with MRI has indicated the effectiveness of this technique for defining great vessel and internal cardiac anatomy in patients with congenital heart disease. This is accomplished without the use of contrast media and is thus a completely noninvasive technique for cardiovascular diagnosis.
beta2-Microglobulin mutations, HLA class I antigen loss, and tumor progression in melanoma.
Authors: D J Hicklin, Z Wang, F Arienti, L Rivoltini, G Parmiani, S Ferrone
Journal: Journal of Clinical Investigation (1998)

The potential negative impact of HLA class I antigen abnormalities on the outcome of T cell-based immunotherapy of melanoma has prompted us to investigate the mechanisms underlying lack of HLA class I antigen expression by melanoma cell lines Me18105, Me9923, and Me1386. Distinct mutations in the beta2-microglobulin (beta2m) gene were identified in each cell line which result in loss of functional beta2m. In Me18105 cells, an aberrant splicing mechanism caused by an A--> G point mutation in the splice acceptor site of intron 1 of the beta2m gene, deletes 11 bp from the beta2m mRNA creating a shift in the reading frame. In Me9923 cells a 14-bp deletion in exon 2 and in Me1386 cells a CT deletion in exon 1 of the beta2m gene produce a frameshift mutation. The beta2m gene mutations identified in Me18105, Me9923, and Me1386 cells were also detected in the surgically removed melanoma lesions from which the cell lines originated. Transfection of each melanoma cell line with a wild-type beta2m gene restored HLA class I antigen expression and, in Me18105 cells, recognition by Melan-A/MART-1-specific, HLA-A2-restricted cytotoxic T lymphocytes. Interestingly, the beta2m mutation present in Me9923 cells that were derived from a metastatic lesion was also found in the Me9923P cell line that originated from the autologous primary lesion. These data suggest that beta2m mutations in melanoma cells may be an early event in progression to the malignant phenotype.
Cardiac specialist to leave Welsh hospital after mediation
Authors: Roger Dobson
Journal: BMJ (2004)

A member of the cardiac theatre team at a Welsh hospital is to leave after an investigation into working relationships in the cardiac unit.

The move at the unit at Swansea's Morriston Hospital, which was closed for a week earlier this year because of what was described as pressure of work (BMJ 2004;328:604 News Extra), comes after the findings of a mediation process.

Members of the team will also get help with “behavioural development,” under a plan of action drawn …
Acquired and Inherited Lipodystrophies
Authors: Abhimanyu Garg
Journal: New England Journal of Medicine (2004)

Lipodystrophies, heterogeneous acquired or inherited disorders characterized by the selective loss of adipose tissue, predispose affected patients to insulin resistance and its attendant complications. This review focuses on the clinical features, underlying pathogenetic mechanisms, and management of various types of acquired and inherited lipodystrophies.
Integrating Prediction Rules Into Clinical Work Flow
Authors: Mitchell H. Katz
Journal: JAMA Internal Medicine (2013)

Thomas G. McGinn, MD, MPH; Lauren McCullagh, MPH; Joseph Kannry, MD; Megan Knaus, MPH; Anastasia Sofianou, MS; Juan P. Wisnivesky, MD, DrPH; Devin M. Mann, MD, MS
Medicare spends billions on "low value" services, US study finds
Authors: M. McCarthy
Journal: BMJ (2014)

Medicare, the US health insurance plan that covers 50 million elderly and disabled people, spends billions of dollars a year on services that provide little or no benefit to patients, a new study claims.1

For the study the researchers identified 26 services that could be identified from Medicare claims data and that had been found to provide low value in a variety of assessments, including those conducted by the American Board of Internal Medicine Foundation’s “Choosing Wisely” initiative, the US Preventive Services Task Force, the UK National Institute for Health and Care Excellence, and the Canadian …
Doctors warn of exodus from Czech Republic and Slovakia
Authors: K. Krosnar
Journal: BMJ (2003)

Doctors' leaders in the Czech Republic and Slovakia are calling on governments to do more to prevent an exodus of doctors once these countries join the European Union next year.

Milan Kubek, chairman of the Czech Doctors' Trade Union, said hospital doctors in particular were set to leave in increasingly large numbers, because of the axeing of borders and work restrictions, compounded by increasing frustration at the health system at home.

“The country already faces a shortage of 550 hospital doctors, and the situation is only set to get worse unless the government acts soon to drastically increase …
A NEW COMBINATION MOUTH-GAG AND TONGUE-DEPRESSOR
Authors: F. H. BRANDT
Journal: JAMA (1910)

Because it is almost impossible for an assistant to hold the tongue down properly in operations on the throat, under general anesthesia, without being in the way of the operator, I have designed an instrument, of simple construction and easy to adjust, which keeps the tongue out of the field of operation. The objection to similar instruments now on the market lies in the impossibility of removing the tongue-depressor without taking out the mouth-gag also. This is important, as conditions may arise during an operation which necessitate the immediate removal of the tongue-depressor. The mouth-gag is the well-known Stubbs-Murdock model, to which I have attached the tongue-depressor, working on a swivel joint, which accommodates it to the base of the tongue, so hard for an assistant to hold down. As seen in the illustration a set-screw is fastened to the lower teeth-plate which controls and fastens the tongue-blade at
What is special about “implicit” and “explicit”?
Authors: Geir Overskeid
Journal: Behavioral and Brain Sciences (1999)

Dienes &amp; Perner present a very interesting analysis of two types of knowledge. It is not clear, however, that the words “implicit” and “explicit” are the best basis on which to build a theory of the two types of knowledge. One is also left uncertain as to whether this theory is the best way of ordering the greatest possible amount of relevant data in a way that yields the simplest account possible.
The contribution of biotechnology toward progress in diagnosis, management, and treatment of allergic diseases
Authors: O. Palomares, R. Crameri, C. Rhyner
Journal: Allergy (2014)

'Biotechnology' has been intuitively used by humans since thousands of years for the production of foods, beverages, and drugs based on the experience without any scientific background. However, the golden era of this discipline emerged only during the second half of the last century. Incredible progresses have been achieved on all fields starting from the industrialization of the production of foods to the discovery of antibiotics, the decipherment of the genetic code, and rational approaches to understand and define the status we now call 'healthy'. The extremely complex interactions between genetic background, life style, and environmental factors influencing our continuously increasing life span have become more and more evident and steadily generate new questions which are only partly answered. Here, we try to summarize the contribution of biotechnology to our understanding, control, and cure of IgE-mediated allergic diseases. We are aware that a review of such a vast topic can never cover all aspects of the progress achieved in the different fields.