tbuckley/cabot-search huggingface dataset:
Dose-Response Effect of a Single Administration of Oral Hexyl-Insulin Monoconjugate 2 in Healthy Nondiabetic Subjects
Authors: Estela Wajcberg, Yoshinori Miyazaki, Curtis Triplitt, Eugenio Cersosimo, Ralph A. DeFronzo
Journal: Diabetes Care (2004)

OBJECTIVE—1) To evaluate the effect of a single oral dose of hexyl-insulin monoconjugate 2 (HIM2) on the rate of whole-body glucose disposal (Rd) and endogenous glucose production (EGP) in healthy nondiabetic subjects, 2) to examine the reproducibility of HIM2 on glucose metabolism, and 3) to compare the results obtained with HIM2 with those using a bioequivalent dose of subcutaneous lispro insulin. RESEARCH DESIGN AND METHODS—Six healthy subjects ([means ± SE] aged 31 ± 5 years and BMI 23.1 ± 3.9 kg/m2) participated in four studies performed in random order on separate days. Subjects ingested a single dose of HIM2 (0.125, 0.5, and 0.75 mg/kg) or received subcutaneous lispro insulin (0.1 units/kg). Studies were performed with [3-3H]glucose, and plasma glucose concentration was maintained at basal levels for 4 h with the euglycemic clamp technique. After 6 weeks, subjects participated in two repeat studies to examine the reproducibility of HIM2 (0.5 mg/kg) and lispro insulin (0.1 units/kg). RESULTS—Fasting plasma insulin (7 μU/ml) increased to a maximum of 102, 321, and 561 μU/ml at 60 min after all three HIM2 doses (0.125, 0.5, and 0.75 mg/kg, respectively). A dose-related decrease in basal EGP was observed as the HIM2 dosage was increased from 0 to 0.125 to 0.5 mg/kg (P &amp;lt; 0.05 vs. each preceding dose). Suppression of EGP was similar with the 0.5- and 0.75-mg/kg HIM2 doses. A dose-related stimulation of basal Rd was observed as the HIM2 dosage was increased from 0 to 0.125 to 0.5 (P &amp;lt; 0.05 vs. each preceding dose) to 0.75 mg/kg (P &amp;lt; 0.10 vs. preceding dose). Rd (0–240 min) was increased by 0.5 mg/kg oral HIM2 to a value similar to 0.1 units/kg lispro insulin. The 0.125-mg/kg HIM2 dose reduced EGP (0–240 min) to a value that was similar to 0.1 units/kg lispro insulin. The variability in the effect of HIM2 and lispro on Rd (25 ± 7 vs. 27 ± 1%, respectively) and on suppression of EGP (19 ± 1 vs. 19 ± 0.7%, respectively) was similar. CONCLUSIONS—Oral HIM2 suppresses EGP and increases tissue Rd in a dose-dependent manner. The effects of HIM2 on EGP and Rd persisted at 240 min, even though plasma insulin concentration had returned to basal levels. Oral HIM2 may provide an effective and reproducible means of controlling postprandial plasma glucose excursions in diabetic patients.
The burden of hepatitis C in the United States
Authors: Ray W. Kim
Journal: Hepatology (2002)

According to the third National Health and Nutrition Examination Survey (NHANES), 3.9 million of the U.S. civilian population have been infected with hepatitis C virus (HCV), of whom 2.7 million (74%) have chronic infection. Hepatitis C virus infection is most common among non-Caucasian men, ages 30 to 49 years. Moreover, the prevalence of antibody to hepatitis C virus in groups not represented in the NHANES sample, such as the homeless or incarcerated, may be as high as 40%. The age-adjusted death rate for non-A, non-B viral hepatitis increased from 0.4 to 1.8 deaths per 100,000 persons per year between 1982 and 1999. In 1999, the first year hepatitis C was reported separately, there were 3,759 deaths attributed to HCV, although this is likely an underestimate. There was a 5-fold increase in the annual number of patients with HCV who underwent liver transplantation between 1990 and 2000. Currently, more than one third of liver transplant candidates have HCV. Inpatient care of HCV-related liver disease has also been increasing. In 1998, an estimated 140,000 discharges listed an HCV-related diagnosis, accounting for 2% of discharges from non-federal acute care hospitals in the United States. The total direct health care cost associated with HCV is estimated to have exceeded $1 billion in 1998. Future projections predict a 4-fold increase between 1990 and 2015 in persons at risk of chronic liver disease ( i.e. , those with infection for 20 years or longer), suggesting a continued rise in the burden of HCV in the United States in the foreseeable future.
Patterns of K-ras mutation in colorectal carcinomas from Iran and Italy (a Gruppo Oncologico dell'Italia Meridionale study): influence of microsatellite instability status and country of origin
Authors: F. Bishehsari, M. Mahdavinia, R. Malekzadeh, F. Verginelli, T. Catalano, M. Sotoudeh, V. Bazan, V. Agnese, D.L. Esposito, L. De Lellis, D. Semeraro, G. Colucci, M. Hormazdi, N. Rakhshani, A. Cama, M. Piantelli, S. Iacobelli, A. Russo, R. Mariani-Costantini
Journal: Annals of Oncology (2006)
Outpatient fractionated ifosfamide, carboplatin and etoposide as salvage therapy in relapsed and refractory non-Hodgkin's and Hodgkin's lymphoma
Authors: M.S. Hertzberg, C. Crombie, W. Benson, J. Taper, D. Gottlieb, K.F. Bradstock
Journal: Annals of Oncology (2006)
Novel agents and regimens for acute myeloid leukemia: 2009 ASH annual meeting highlights
Authors: Xiongpeng Zhu, Yuehua Ma, Delong Liu
Journal: Journal of Hematology & Oncology (2010)

Prognostic markers, such as NPM1, Flt3-ITD, and cytogenetic abnormalities have made it possible to formulate aggressive treatment plans for unfavorable acute myeloid leukemia (AML). However, the long-term survival of AML with unfavorable factors remains unsatisfactory. The latest data indicate that the standard dose of daunorubicin (DNR) at 45 mg/m2 is inferior to high dose 90 mg/m2 for induction therapy. The rates of complete remission and overall survival are significantly better in the high dose induction regimen. New regimens exploring the new liposomal encapsulation of Ara-C and DNR as well as addition of gemtuzumab ozogamicin monoclonal antibody have been studied. New agents, including the nucleoside analogues (clofarabine, sapacitabine, elacytarabine), FLT3 inhibitor (sorafenib), farnesyl-transferase inhibitor (tipifarnib), histone deacetylase inhibitor (vorinostat), lenalidomide, as well as DNA methyltransferase inhibitors (decitabine, azacitidine), were recently reported for AML treatment in the 2009 ASH annual meeting. This review also summarizes the updates of the clinical trials on novel agents including voreloxin, AS1413, behenoylara-C, ARRY520, ribavirin, AZD1152, AZD6244, and terameprocol (EM-1421) from the 2009 ASH annual meeting.
What is a sports medicine specialist?
Authors: P Schur
Journal: British Journal of Sports Medicine (2000)

<i>Introduction:</i> The electronic Primary Care Research Network (ePCRN) enrolled PBRN researchers in a feasibility trial to test the functionality of the network’s electronic architecture and investigate error rates associated with two data entry strategies used in clinical trials. <i>Methods:</i> PBRN physicians and research assistants who registered with the ePCRN were eligible to participate. After online consent and randomization, participants viewed simulated patient records, presented as either abstracted data (short form) or progress notes (long form). Participants transcribed 50 data elements onto electronic case report forms (CRFs) without integrated field restrictions. Data errors were analyzed. <i>Results:</i> Ten geographically dispersed PBRNs enrolled 100 members and completed the study in less than 7 weeks. The estimated overall error rate if field restrictions had been applied was 2.3%. Participants entering data from the short form had a higher rate of correctly entered data fields (94.5% vs 90.8%, <i>P</i> = .004) and significantly more error-free records (<i>P</i> = .003). <i>Conclusions:</i> Feasibility outcomes integral to completion of an Internet-based, multisite study were successfully achieved. Further development of programmable electronic safeguards is indicated. The error analysis conducted in this study will aid design of specific field restrictions for electronic CRFs, an important component of clinical trial management systems.
Hepatotoxicity of antituberculosis drugs.
Authors: L. P. Ormerod, C. Skinner, J. Wales
Journal: Thorax (1996)

EditorialsHepatotoxicity of antituberculosis drugs Her Majesty's Coroner for Birmingham, where there is a major liver unit, has drawn attention to the number of deaths from liver failure associated with the antituberculosis drugs,' and has called for greater awareness by both patients and general practitioners of the occasional cases of hepatotoxicity.This was followed by a reminder from the Committee on Safety of Medicine (CSM) of fatal hepatic reactions.2The CSM advice was that liver function tests should be undertaken before treatment and, if abnormal, repeated during treatment, and that liver function should be checked in patients who develop symptoms or signs suggestive of hepatitis, or who become generally unwell during treatment.This advice differs from that given by the Joint Tuberculosis Committee's chemotherapy guidelines3 which state:"Liver function should be checked pretreatment.Transient increases in hepatic transaminases are common after the start of treatment and require no action unless the patient has symptoms of hepatitis or jaundice.After the initial measurement liver function does not need to be monitored routinely except in alcoholics and those with other liver diseases.If jaundice or other symptoms of hepatitis develop all drugs must be stopped.It is usually possible to restart all drugs after liver function returns to pretreatment levels.If symptoms recur, however, the drugs should be introduced individually, once liver function has returned to normal, at a lower dose initially together with at least one drug which is unlikely to cause hepatic dysfunction (streptomycin or ethambutol)."ill
Treatment of Medulloblastoma with Hedgehog Pathway Inhibitor GDC-0449
Authors: Charles M. Rudin, Christine L. Hann, John Laterra, Robert L. Yauch, Christopher A. Callahan, Ling Fu, Thomas Holcomb, Jeremy Stinson, Stephen E. Gould, Barbara Coleman, Patricia M. LoRusso, Daniel D. Von Hoff, Frederic J. de Sauvage, Jennifer A. Low
Journal: New England Journal of Medicine (2009)

Medulloblastoma is the most common malignant brain tumor in children. Aberrant activation of the hedgehog signaling pathway is strongly implicated in the development of some cases of medulloblastoma. A 26-year-old man with metastatic medulloblastoma that was refractory to multiple therapies was treated with a novel hedgehog pathway inhibitor, GDC-0449; treatment resulted in rapid (although transient) regression of the tumor and reduction of symptoms. Molecular analyses of tumor specimens obtained before treatment suggested that there was activation of the hedgehog pathway, with loss of heterozygosity and somatic mutation of the gene encoding patched homologue 1 (PTCH1), a key negative regulator of hedgehog signaling.
Antireflux Procedures for Gastroesophageal Reflux Disease in Children
Authors: Jarod McAteer, Cindy Larison, Cabrini LaRiviere, Michelle M. Garrison, Adam B. Goldin
Journal: JAMA Surgery (2013)

IMPORTANCE Gastroesophageal reflux disease (GERD) is a common diagnosis in infants and children, but no objective criteria exist to guide the diagnosis and treatment of this disease in this population.The extent to which age influences decisions about surgical treatment in childhood GERD is unknown.OBJECTIVE To identify factors associated with progression to antireflux procedures (ARPs) in children hospitalized with GERD.DESIGN, SETTING, AND PARTICIPANTS Retrospective cohort study using inpatient data from 41 US children's hospitals in the Pediatric Health Information System database.We included patients younger than 18 years discharged from January 1, 2002, through December 31, 2010, with primary diagnostic codes for GERD (n = 141 190).We evaluated demographics, comorbidities, and diagnostic procedures descriptively and with a multivariate Cox proportional hazards regression model. EXPOSURE Patient age. MAIN OUTCOMES AND MEASURES Proportional hazard of progression to ARP during admission.RESULTS Of the 141 190 patients meeting study criteria, 11 621 (8.2%) underwent ARPs during the study period.More than half of patients undergoing ARPs (52.7%) were 6 months or younger.Although most patients in the ARP group had preoperative upper gastrointestinal tract fluoroscopy (65.0%), these patients did not undergo a uniform workup.The hazard of progression to an ARP was significantly decreased in children aged 7 months to 4 years (hazard ratio, 0.63 [P < .001])and 5 to 17 years (0.43 [P < .001])relative to children younger than 2 months.Hazard ratios were independently increased for comorbid diagnoses of failure to thrive, neurodevelopmental delay, cardiopulmonary anomalies, cerebral palsy, and aspiration pneumonia and among patients with tracheoesophageal fistula and diaphragmatic hernia.Each additional GERD-related hospitalization was associated with a 10% increased risk of an ARP.CONCLUSIONS AND REVELANCE Antireflux procedures are most commonly performed in children during a period of life when regurgitation is normal and physiologic and objective measures of GERD are difficult to interpret.To identify meaningful outcomes after ARP, indications must be clear and standardized.We must clarify the appropriate workup for infants and young children with GERD and better define "failure of medical management" in this population.
A single mutation in the GSTe2 gene allows tracking of metabolically based insecticide resistance in a major malaria vector
Authors: Jacob M Riveron, Cristina Yunta, Sulaiman S Ibrahim, Rousseau Djouaka, Helen Irving, Benjamin D Menze, Hanafy M Ismail, Janet Hemingway, Hilary Ranson, Armando Albert, Charles S Wondji
Journal: Genome biology (2014)

Abstract Background Metabolic resistance to insecticides is the biggest threat to the continued effectiveness of malaria vector control. However, its underlying molecular basis, crucial for successful resistance management, remains poorly characterized. Results Here, we demonstrate that the single amino acid change L119F in an upregulated glutathione S-transferase gene, GSTe2 , confers high levels of metabolic resistance to DDT in the malaria vector Anopheles funestus . Genome-wide transcription analysis revealed that GSTe2 was the most over-expressed detoxification gene in DDT and permethrin-resistant mosquitoes from Benin. Transgenic expression of GSTe2 in Drosophila melanogaster demonstrated that over-transcription of this gene alone confers DDT resistance and cross-resistance to pyrethroids. Analysis of GSTe2 polymorphism established that the point mutation is tightly associated with metabolic resistance to DDT and its geographical distribution strongly correlates with DDT resistance patterns across Africa. Functional characterization of recombinant GSTe2 further supports the role of the L119F mutation, with the resistant allele being more efficient at metabolizing DDT than the susceptible one. Importantly, we also show that GSTe2 directly metabolizes the pyrethroid permethrin. Structural analysis reveals that the mutation confers resistance by enlarging the GSTe2 DDT-binding cavity, leading to increased DDT access and metabolism. Furthermore, we show that GSTe2 is under strong directional selection in resistant populations, and a restriction of gene flow is observed between African regions, enabling the prediction of the future spread of this resistance. Conclusions This first DNA-based metabolic resistance marker in mosquitoes provides an essential tool to track the evolution of resistance and to design suitable resistance management strategies.
Furin-Like Proprotein Convertases Are Central Regulators of the Membrane Type Matrix Metalloproteinase–Pro-Matrix Metalloproteinase-2 Proteolytic Cascade in Atherosclerosis
Authors: Philipp Stawowy, Heike Meyborg, Dietger Stibenz, Núbia Borges Pereira Stawowy, Mattias Roser, Usan Thanabalasingam, John P. Veinot, Michel Chrétien, Nabil G. Seidah, Eckart Fleck, Kristof Graf
Journal: Circulation (2005)

Accumulation of macrophages and their in situ expression of matrix metalloproteinases (MMPs) are important determinants of plaque stability. Activation of membrane-bound MT1-MMP, the major activator of pro-MMP-2, requires intracellular endoproteolytic cleavage of its precursor protein. This type of activation typically requires suitable furin-like proprotein convertases (PCs), specifically furin and PC5. The present study was done to investigate the function of MT1-MMP as well as furin-like PCs in mononuclear inflammatory cells.Macrophage differentiation of human monocytic THP-1 cells was accompanied by increased expression of furin, PC5, and MT1-MMP. Some pro-MMP-2 activation was found in macrophages, but pro-MMP-2 level or activation was not enhanced after stimulation with the proinflammatory mediators tumor necrosis factor-alpha or lipopolysaccharide. However, culturing of macrophages in conditioned medium from serum-starved vascular smooth muscle cells, which constitutively secrete pro-MMP-2, resulted in a strong pro-MMP-2 activation. Inhibition of furin-like PCs with the specific pharmacological inhibitor decanoyl-RVKR-chloromethylketone (dec-CMK) inhibited MT1-MMP activation in macrophages. Dec-CMK or furin-specific small interfering RNA significantly inhibited macrophage MT1-MMP-dependent activation of vascular smooth muscle cell-derived pro-MMP-2. Flow cytometry demonstrated that human circulating monocytes express furin and PC5, and MT1-MMP and immunohistochemistry revealed their colocalization in macrophages in advanced human atherosclerotic lesions.Furin-like PCs (furin and PC5) play a central role in a MT-MMP-MMP-2 proteolytic cascade, involving provision of macrophage MT1-MMP for the activation of pro-MMP-2 synthesized by other cells. Furin and PC5 are expressed in human peripheral blood mononuclear cells and colocalize with MT1-MMP in macrophages in the atherosclerotic plaque, supporting the hypothesis that they are potential targets in atherosclerosis.
RELATCH: relative optimality in metabolic networks explains robust metabolic and regulatory responses to perturbations
Authors: Joonhoon Kim, Jennifer L Reed
Journal: Genome biology (2012)

Abstract Predicting cellular responses to perturbations is an important task in systems biology. We report a new approach, RELATCH, which uses flux and gene expression data from a reference state to predict metabolic responses in a genetically or environmentally perturbed state. Using the concept of relative optimality, which considers relative flux changes from a reference state, we hypothesize a relative metabolic flux pattern is maintained from one state to another, and that cells adapt to perturbations using metabolic and regulatory reprogramming to preserve this relative flux pattern. This constraint-based approach will have broad utility where predictions of metabolic responses are needed.
Prevalence, Characteristics, and Prognostic Significance of <i>HFE</i> Gene Mutations in Type 2 Diabetes
Authors: Timothy M.E. Davis, John Beilby, Wendy A. Davis, John K. Olynyk, Gary P. Jeffrey, Enrico Rossi, Conchita Boyder, David G. Bruce
Journal: Diabetes Care (2008)

OBJECTIVE—To examine the relationship between iron status, hereditary hemochromatosis (HFE) gene mutations, and clinical features and outcomes of type 2 diabetes in a well-characterized representative sample of community-based patients. RESEARCH DESIGN AND METHODS—HFE genotype data were available for 1,245 type 2 diabetic patients from the longitudinal observational Fremantle Diabetes Study (FDS), representing 96.2% of the total FDS type 2 diabetes cohort. Data were collected at recruitment between 1993 and 1996 and annually until the end of June 2001. Hospitalization and mortality data were available until the end of June 2006. The presence of the C282Y HFE mutation was determined in all subjects and H63D in C282Y heterozygotes. Fasting serum iron, transferrin, and ferritin were measured in all C282Y homozygotes and C282Y/H63D heterozygotes and in 286 randomly selected wild-type subjects. Multiple logistic regression analysis was performed to determine independent baseline associates of prevalent complications (myocardial infarction, cerebrovascular disease, retinopathy, neuropathy, and nephropathy), as was Cox proportional hazards modeling to determine predictors of incident complications and mortality. RESULTS—Although there were expected positive associations between HFE gene mutations and serum iron and transferrin saturation, there were no independent positive associations between HFE gene status and either microvascular or macrovascular complications in cross-sectional and longitudinal analyses. HFE gene status did not independently predict cardiac or all-cause mortality. Measures of iron metabolism including serum ferritin were not associated with combined microvascular or macrovascular end points. CONCLUSIONS—Directed screening for iron overload and/or HFE mutations appears unwarranted in patients with type 2 diabetes.
Vectorcardiographic quantification of infarct size in baboons.
Authors: S A Wickline, J J McNamara
Journal: Circulation (1978)

A vectorcardiographic method has been developed for determining the absolute size of myocardial infarcts in baboons resulting from coronary artery ligation. Spatial area (mvolt . msec) and voltage (mvolt) difference-vectors were obtained for 8 animals by measuring the voltage loss and temporal deviation from pre- to post-ligation McFee scalar leads. The difference vectors were then correlated with the absolute infarct volumes, which were derived by histological assessment 10 days after ligation. Absolute lesion sizes ranged from approximately 2 cc to 14 cc, involving 10-30% of ventricular muscle mass. The correlation coefficient, r, for the area deviation index was 0.98 (SEE = +/- 0.24 cc); and for the voltage deviation index, r was 0.92 (SEE = +/- 0.51 cc). These results demonstrate that the severity of infarction can be accurately determined if prepathological vectorcardiograms are available.
US teenagers think oral sex isn't real sex
Authors: Janice Hopkins Tanne
Journal: BMJ (2005)

A study of nearly 600 young California teenagers indicates that, having been told to be abstinent and warned of dangers of sex such as pregnancy and sexually transmitted diseases, they have decided that oral sex is the safest choice ( Pediatrics 2005;115:845-51).

Previous studies indicated that many young people choose to have oral sex and don't consider it “real sex.” In 1999 a study in the journal of the American Medical Association showed that US university students didn't think oral sex was real sex ( JAMA 1999:281;275-7).

Publication of that study coincided with the impeachment trial of Bill Clinton, at which he denied sexual relations with Monica Lewinsky, who had performed oral sex on him. Dr George Lundberg, editor of JAMA, was …