tbuckley/cabot-search huggingface dataset:
Relation of Interferon Therapy and Hepatocellular Carcinoma in Patients with Chronic Hepatitis C
Authors: Yasuharu Imai
Journal: Annals of Internal Medicine (1998)

Background: The effect of interferon therapy on the incidence of hepatocellular carcinoma in chronic hepatitis C is poorly defined. Objective: To compare the incidence of hepatocellular carcinoma in interferon-treated patients with chronic hepatitis C to that of historical controls and to examine whether response to therapy is related to incidence of hepatocellular carcinoma in patients with chronic hepatitis C. Design: Retrospective cohort study. Setting: One university hospital and seven university-affiliated hospitals. Patients: 419 consecutive patients with chronic hepatitis C who started interferon therapy between January 1992 and December 1993 (interferon group) and 144 patients with chronic hepatitis C who had liver biopsy between January 1986 and December 1989 and did not receive interferon (controls). Intervention: Patients in the interferon group received human lymphoblastoid interferon, recombinant interferon-α 2a, or recombinant interferon-α 2b for 6 months. Measurements: The end point was development of hepatocellular carcinoma on abdominal ultrasonography or computed tomography. Sustained response was defined as persistent normalization of alanine aminotransferase (ALT) levels during interferon therapy and follow-up. Relapse was defined as a normal serum ALT level at the end of treatment with an increase to an abnormal level after cessation of treatment. Nonresponse included all other ALT patterns. Results: Median follow-up in the interferon and control groups was 47.6 and 46.8 months, respectively. During follow-up, hepatocellular carcinoma was found in 28 interferon-treated patients and 19 controls. Cox proportional-hazards regression analysis that included all patients revealed that interferon therapy (P = 0.041), older age (P = 0.003), greater histologic activity (P = 0.029), and higher histologic stage (P = 0.049) were independent factors associated with the development of hepatocellular carcinoma. The risk ratios for development of hepatocellular carcinoma in patients with sustained response, relapse, and nonresponse were 0.06 (95% CI, 0.01 to 0.46), 0.51 (CI, 0.20 to 1.27), and 0.95 (CI, 0.48 to 1.84), respectively, compared with controls. Conclusions: The incidence of hepatocellular carcinoma was lower in patients with sustained response to interferon therapy than historical controls and nonresponders. Interferon therapy may decrease the risk for hepatocellular carcinoma in patients with chronic hepatitis C.
Phase I Clinical Trial of Recombinant Human Endostatin Administered as a Short Intravenous Infusion Repeated Daily
Authors: Joseph P. Eder, Jeffrey G. Supko, Jeffrey W. Clark, Thomas A. Puchalski, Rocio Garcia-Carbonero, David P. Ryan, Lawrence N. Shulman, Joann Proper, Moira Kirvan, Barbara Rattner, Susan Connors, Mary T. Keogan, Milos J. Janicek, William E. Fogler, Lowell Schnipper, Nancy Kinchla, Carolyn Sidor, Eric Phillips, Judah Folkman, Donald W. Kufe
Journal: Journal of Clinical Oncology (2002)

To perform a phase I trial of recombinant human endostatin (rhEndostatin; EntreMed, Rockville, MD) given as a daily 20-minute intravenous (IV) injection in adult patients with refractory solid tumors.The daily dose was increased from 15 to 240 mg/m(2) by a factor of 100% in cohorts of three patients. In the absence of dose-limiting toxicity, uninterrupted treatment was continued until the tumor burden increased by more than 50% from baseline. Correlative studies included dynamic contrast-enhanced magnetic resonance imaging of tumor blood flow, urinary vascular endothelial growth factor and basic fibroblast growth factor levels, rhEndostatin serum pharmacokinetics, and monitoring of circulating antibodies to rhEndostatin.There were no notable treatment related toxicities among 15 patients receiving a total of 50 monthly cycles of rhEndostatin. One patient with a pancreatic neuroendocrine tumor had a minor response and two patients showed disease stabilization. Linearity in the pharmacokinetics of rhEndostatin was indicated by dose-proportionate increases in the area under the curve for the first dose and the peak serum concentration at steady state. Daily systemic exposure to rhEndostatin in patients receiving 240 mg/m(2)/d was approximately 50% lower than that provided by the therapeutically optimal dose in preclinical studies.rhEndostatin administered as a 20-minute daily IV injection at doses up to 240 mg/m(2) showed no significant toxicities. Evidence of clinical benefit was observed in three patients. Due to high variability between the peak and trough serum concentrations associated with the repeated short IV infusion schedule, daily serum drug levels only briefly exceeded concentrations necessary for in vitro antiangiogenic effects.
Lower Fasting Muscle Mitochondrial Activity Relates to Hepatic Steatosis in Humans
Authors: Julia Szendroedi, Kirti Kaul, Lisa Kloock, Klaus Straßburger, Albrecht Ingo Schmid, Marek Chmelik, Michaela Kacerovsky, Gertrud Kacerovsky-Bielesz, Thomas Prikoszovich, Attila Brehm, Martin Krššák, Stephan Gruber, Michael Krebs, Alexandra Kautzky-Willer, Ewald Moser, Giovanni Pacini, Michael Roden
Journal: Diabetes Care (2013)

OBJECTIVE Muscle insulin resistance has been implicated in the development of steatosis and dyslipidemia by changing the partitioning of postprandial substrate fluxes. Also, insulin resistance may be due to reduced mitochondrial function. We examined the association between mitochondrial activity, insulin sensitivity, and steatosis in a larger human population. RESEARCH DESIGN AND METHODS We analyzed muscle mitochondrial activity from ATP synthase flux (fATP) and ectopic lipids by multinuclei magnetic resonance spectroscopy from 113 volunteers with and without diabetes. Insulin sensitivity was assessed from M values using euglycemic-hyperinsulinemic clamps and/or from oral glucose insulin sensitivity (OGIS) using oral glucose tolerance tests. RESULTS Muscle fATP correlated negatively with hepatic lipid content and HbA1c. After model adjustment for study effects and other confounders, fATP showed a strong negative correlation with hepatic lipid content and a positive correlation with insulin sensitivity and fasting C-peptide. The negative correlation of muscle fATP with age, HbA1c, and plasma free fatty acids was weakened after adjustment. Body mass, muscle lipid contents, plasma lipoproteins, and triglycerides did not associate with fATP. CONCLUSIONS The association of impaired muscle mitochondrial activity with hepatic steatosis supports the concept of a close link between altered muscle and liver energy metabolism as early abnormalities promoting insulin resistance.
Comparison of treatment outcomes in community-acquired pneumonia patients treated with beta lactam-macrolide combination versus fluoroquinolone monotherapy
Authors: Oguz Kilinc, Oznur Soylar, Aykut Cilli, Aysin Sakar, Sezai Tasbakan, Hulya Ellidokuz, Burcu Celenk, Cemile Cetinkaya, Canan Gunduz, Abdullah Sayiner
Journal: European Respiratory Journal (2012)

The clinical outcomes of patients with community-acquired pneumonia treated in accordance with the recommendations of Turkish Thoracic Society (TTS) guidelines and who had received beta lactam-macrolide combination or fluoroquinolone (FQ) monotherapy were evaluated using the data from four contributing sites to the TURCAP database of TTS Assembly of Respiratory Infections. A total of 343 patients was included. Of these patients, 63.6% had received combination treatment and 36.4% had received FQ monotherapy. There was no difference between the two groups regarding age, gender and comorbidities. However, the mean Pneumonia Severity Index (PSI) scores were 101.8±35.8 and 91.0±28.9 (p=0.006) and CURB-65 scores were 2.3±1.0 and 2.0±0.8 (p=0.002), respectively. The length of hospital stay was 9.5±6.1 days in the combination and 8.5±4.4 days in the FQ groups (p=0.24). The rates for cure, partial improvement and mortality were 59.1%, 28.2%, 12.8% for the combination group versus 72.6%, 24.2%, 3.2% for the FQ group, respectively. There was no significant difference between the improvement rates; on the other hand, the mortality was higher in the combination group (p=.0.03). Logistic regression analysis showed that mortality was associated with PSI score and not with the choice of antibiotic treatment. In this retrospective analysis of TURCAP database, the clinical success rates were similar in patients who received a combination of beta lactam and macrolide and fluoroquinolone monotherapy. The lower mortality observed in the latter group was found to be associated with less severe disease at presentation.
Functional Regulatory T Cells Produced by Inhibiting Cyclic Nucleotide Phosphodiesterase Type 3 Prevent Allograft Rejection
Authors: Gang Feng, Satish N. Nadig, Liselotte Bäckdahl, Stephan Beck, Ross S. Francis, Alexandru Schiopu, Andrew Whatcott, Kathryn J. Wood, Andrew Bushell
Journal: Science Translational Medicine (2011)

A clinically approved agent can generate ex vivo graft-reactive, functional mouse and human regulatory T cells.
Safety and efficacy of the HIV-1 attachment inhibitor prodrug BMS-663068 in treatment-experienced individuals: 24 week results of AI438011, a phase 2b, randomised controlled trial
Authors: Jacob P Lalezari, Gulam H Latiff, Cynthia Brinson, Juan Echevarría, Sandra Treviño-Pérez, Johannes R Bogner, Melanie Thompson, Jan Fourie, Otto A Sussmann Pena, Fernando C Mendo Urbina, Marcelo Martins, Iulian G Diaconescu, David A Stock, Samit R Joshi, George J Hanna, Max Lataillade
Journal: The Lancet HIV (2015)
Hyperosmolar Hyperglycemic State: A Historic Review of the Clinical Presentation, Diagnosis, and Treatment
Authors: Francisco J. Pasquel, Guillermo E. Umpierrez
Journal: Diabetes Care (2014)

The hyperosmolar hyperglycemic state (HHS) is the most serious acute hyperglycemic emergency in patients with type 2 diabetes. von Frerichs and Dreschfeld described the first cases of HHS in the 1880s in patients with an “unusual diabetic coma” characterized by severe hyperglycemia and glycosuria in the absence of Kussmaul breathing, with a fruity breath odor or positive acetone test in the urine. Current diagnostic HHS criteria include a plasma glucose level &amp;gt;600 mg/dL and increased effective plasma osmolality &amp;gt;320 mOsm/kg in the absence of ketoacidosis. The incidence of HHS is estimated to be &amp;lt;1% of hospital admissions of patients with diabetes. The reported mortality is between 10 and 20%, which is about 10 times higher than the mortality rate in patients with diabetic ketoacidosis (DKA). Despite the severity of this condition, no prospective, randomized studies have determined best treatment strategies in patients with HHS, and its management has largely been extrapolated from studies of patients with DKA. There are many unresolved questions that need to be addressed in prospective clinical trials regarding the pathogenesis and treatment of pediatric and adult patients with HHS.
MicroRNA-204 critically regulates carcinogenesis in malignant peripheral nerve sheath tumors
Authors: Meng Gong, Junrong Ma, Mi Li, Mingliang Zhou, Janet M. Hock, Xijie Yu
Journal: Neuro-Oncology (2012)

Malignant peripheral nerve sheath tumors (MPNSTs) are highly aggressive soft tissue sarcomas accounting for 3%–10% of all soft tissue sarcomas. Neurofibromatosis type 1 (NF1) is the most important known risk factor. MPNSTs are often diagnosed at an advanced stage when distant metastases have developed. Although surgical resection remains the main treatment for MPNSTs, complete surgical resection is rarely possible. The prognosis for patients with MPNSTs is poor. There is an urgent need for improved therapies. To this end, we investigated whether microRNA (miR), specifically miR-204, might be implicated in MPNSTs because it is located at a cancer-associated genomic region exhibiting high frequency of loss of heterozygosity in tumors. We show that miR-204 expression is downregulated in NF1 and non-NF1 MPNST tumor tissues and in tumor cell lines. Restoring miR-204 expression in MPNST cell lines STS26T (non-NF1), ST88-14 (NF1), and T265p21 (NF1) significantly reduces cellular proliferation, migration, and invasion in vitro. Restoring miR-204 expression in STS26T decreases tumor growth and malignant progression in vivo. We also report that miR-204 inhibits Ras signaling and expression of high mobility group gene A2. These findings support the hypothesis that miR-204 plays critical roles in MPNST development and tumor progression. miR-204 may represent a novel biomarker for diagnosis and a candidate target with which to develop effective therapies for MPNSTs.
HIV Transmission
Authors: Carl W. Davis, Robert W. Doms
Journal: The Journal of Experimental Medicine (2004)

In the absence of an effective vaccine, educational or interventional strategies that decrease sexual transmission of HIV hold the greatest promise for slowing infection rates. Although a safe and effective microbicide could greatly help in this regard, progress in this area has been disappointing with microbicide development often failing to take into account advances in our understanding of how HIV is transmitted and infects cells. In this issue, Hu et al. demonstrate that HIV infection of human cervical tissue ex vivo can be prevented not only by using antibodies that target the virus but by a cocktail of compounds that target the cell surface receptors to which the virus binds, thus providing a basis for the design of microbicides that prevent virus infection in a highly specific manner (1).
Endothelium-Derived Hyperpolarizing Factor Synthase (Cytochrome P450 2C9) Is a Functionally Significant Source of Reactive Oxygen Species in Coronary Arteries
Authors: Ingrid Fleming, U. Ruth Michaelis, Daniel Bredenkötter, Beate Fisslthaler, Faramarz Dehghani, Ralf P. Brandes, Rudi Busse
Journal: Circulation Research (2001)

In the porcine coronary artery, a cytochrome P450 (CYP) isozyme homologous to CYP 2C8/9 has been identified as an endothelium-derived hyperpolarizing factor (EDHF) synthase. As some CYP enzymes are reported to generate reactive oxygen species (ROS), we hypothesized that the coronary EDHF synthase may modulate vascular homeostasis by the simultaneous production of ROS and epoxyeicosatrienoic acids. In bradykinin-stimulated coronary arteries, antisense oligonucleotides against CYP 2C almost abolished EDHF-mediated responses but potentiated nitric oxide (NO)-mediated relaxation. The selective CYP 2C9 inhibitor sulfaphenazole and the superoxide anion (O(2-)) scavengers Tiron and nordihydroguaretic acid also induced a leftward shift in the NO-mediated concentration-relaxation curve to bradykinin. CYP activity and O(2-) production, determined in microsomes prepared from cells overexpressing CYP 2C9, were almost completely inhibited by sulfaphenazole. Sulfaphenazole did not alter the activity of either CYP 2C8, the leukocyte NADPH oxidase, or xanthine oxidase. ROS generation in coronary artery rings, visualized using either ethidium or dichlorofluorescein fluorescence, was detected under basal conditions. The endothelial signal was attenuated by CYP 2C antisense treatment as well as by sulfaphenazole. In isolated coronary endothelial cells, bradykinin elicited a sulfaphenazole-sensitive increase in ROS production. Although 11,12 epoxyeicosatrienoic acid attenuated the activity of nuclear factor-kappaB in cultured human endothelial cells, nuclear factor-kappaB activity was enhanced after the induction or overexpression of CYP 2C9, as was the expression of vascular cell adhesion molecule-1. These results suggest that a CYP isozyme homologous to CYP 2C9 is a physiologically relevant generator of ROS in coronary endothelial cells and modulates both vascular tone and homeostasis.
Liposome-mediated CFTR gene transfer to the nasal epithelium of patients with cystic fibrosis
Authors: Natasha J. Caplen, Eric W.F.W. Alton, Peter G. Mddleton, Julia R. Dorin, Barbara J. Stevenson, Xiang Gao, Stephen R. Durham, Peter K. Jeffery, Margaret E. Hodson, Charles Coutelle, Leaf Huang, David J. Porteous, Robert Williamson, Duncan M. Geddes
Journal: Nature Medicine (1995)
Role of Adiposity and Lifestyle in the Relationship Between Family History of Diabetes and 20-Year Incidence of Type 2 Diabetes in U.S. Women
Authors: Esther van 't Riet, Jacqueline M. Dekker, Qi Sun, Giel Nijpels, Frank B. Hu, Rob M. van Dam
Journal: Diabetes Care (2010)

OBJECTIVE To evaluate to what extent the association between family history of diabetes and risk of type 2 diabetes can be explained by excess adiposity and lifestyle risk factors. RESEARCH DESIGN AND METHODS We analyzed data from 73,227 women who participated in the Nurses' Health Study cohort. A family history of diabetes was defined as having at least one first-degree family member with diabetes. Lifestyle factors, weight, and height were assessed by using validated questionnaires, and BMI was calculated. The relative risk of type 2 diabetes was estimated using Cox proportional hazards analysis. RESULTS We documented 5,101 cases of type 2 diabetes during 20 years of follow-up. The age-adjusted relative risk of type 2 diabetes in participants with a family history was 2.27 (95% CI 2.14–2.40) compared with the risk in those without a family history of diabetes. Participants with a family history of diabetes had a higher BMI and were more likely to have a parental history of obesity. BMI explained 21.1% (19.4–22.9) of the association between family history of diabetes and risk of type 2 diabetes. Intakes of red meat, alcohol, and sugar-sweetened beverages explained 1.1% (0.8–1.3), 4.8% (4.3–5.3), and 2.8% (2.4–3.2) of this association, respectively. CONCLUSIONS These results suggest that excess adiposity and, to a lesser extent, specific dietary habits can explain a substantial part of the association between having a family history of diabetes and risk of type 2 diabetes.
A 27-Amino-Acid Synthetic Peptide Corresponding to the NH2-Terminal Zinc-Binding Domain of Endostatin Is Responsible for Its Antitumor Activity
Authors: Robert M. Tjin Tham Sjin, Ronit Satchi-Fainaro, Amy E. Birsner, V.M. Sadagopa Ramanujam, Judah Folkman, Kashi Javaherian
Journal: Cancer Research (2005)

Abstract The first recombinant endostatin that elicited strong antitumor activity was expressed in Escherichia coli and administered as a suspension. Under these conditions, the protein retained its full antiangiogenic activity. Lack of requirement for a folded structure prompted us to investigate antitumor properties of synthetic peptides corresponding to different regions of endostatin. Here, we show that the entire antitumor, antimigration, and antipermeability activities of endostatin are mimicked by a 27-amino-acid peptide corresponding to the NH2-terminal domain of endostatin. This peptide contains three histidines that are responsible for zinc binding. Mutations of the zinc-binding histidines abolished its antitumor and antimigration activities, but not antipermeability properties.
Efficacy of an Artificial Neural Network–Based Approach to Endoscopic Ultrasound Elastography in Diagnosis of Focal Pancreatic Masses
Authors: Adrian Săftoiu, Peter Vilmann, Florin Gorunescu, Jan Janssen, Michael Hocke, Michael Larsen, Julio Iglesias–Garcia, Paolo Arcidiacono, Uwe Will, Marc Giovannini, Cristoph F. Dietrich, Roald Havre, Cristian Gheorghe, Colin McKay, Dan Ionuţ Gheonea, Tudorel Ciurea
Journal: Clinical Gastroenterology and Hepatology (2011)
Fatigue, Insufficiency, and Pathologic Fractures
Authors: Richard L. Pentecost, Robert A. Murray, Hanes H. Brindley
Journal: JAMA (1964)

A partial or complete fracture which results from the inherent inability of bone to withstand stress applied without violence in a rhythmical, repeated, subthreshold manner is a "stress fracture." Because numerous terms have been used in the medical literature to designate the two types of stress fractures, the following classification is recommended. A "fatigue fracture" occurs when abnormal stress is applied to bone with normal elastic resistance. An "insufficiency fracture" is produced by normal or physiological stress applied to bone with deficient elastic resistance. Fatigue and insufficiency fractures occur most frequently in the weight-bearing bones. The term "pathologic fracture" should be limited to any fracture in bone weakened by tumor.
Outcomes with the polymer-based paclitaxel-eluting TAXUS stent in patients with diabetes mellitus
Authors: James B. Hermiller, Albert Raizner, Louis Cannon, Paul A. Gurbel, Michael A. Kutcher, S. Chiu Wong, Mary E. Russell, Stephen G. Ellis, Roxana Mehran, Gregg W. Stone
Journal: Journal of the American College of Cardiology (2005)
Clinical Significance of Urinary Liver-Type Fatty Acid–Binding Protein in Diabetic Nephropathy of Type 2 Diabetic Patients
Authors: Atsuko Kamijo-Ikemori, Takeshi Sugaya, Takashi Yasuda, Takehiro Kawata, Akio Ota, Shinobu Tatsunami, Ruriko Kaise, Toshihiko Ishimitsu, Yasushi Tanaka, Kenjiro Kimura
Journal: Diabetes Care (2011)

Urinary liver-type fatty acid-binding protein (L-FABP) is a promising indicator of tubular but not glomerular damage. The aim of this study was to evaluate the clinical usefulness of urinary L-FABP as a prognostic biomarker in impaired diabetic nephropathy in type 2 diabetes.This investigation involved a cross-sectional and longitudinal analysis of the relationship between urinary L-FABP levels and progressive nephropathy. Urinary L-FABP was measured with enzyme-linked immunosorbent assay. In the cross-sectional analysis, the association of urinary L-FABP, with the severity of diabetic nephropathy, was investigated in 140 patients with type 2 diabetes and in 412 healthy control subjects. Of the patients in the former study, 104 have been followed for 4 years. The progression of diabetic nephropathy was defined as progressive albuminuria, end-stage renal disease, or induction of hemodialysis.Urinary L-FABP levels were progressively increased in subjects with normo-, micro-, or macroalbuminuria and further increased in patients with end-stage renal disease. In the longitudinal analysis, high urinary L-FABP levels were associated with the increase in albuminuria, progression to end-stage renal disease, or induction of hemodialysis. This was particularly demonstrated in the subgroup of patients without renal dysfunction (n = 59), where high urinary L-FABP levels were associated with the progression of diabetic nephropathy.Urinary L-FABP accurately reflected the severity of diabetic nephropathy in type 2 diabetes, and its level was high in the patients with normoalbuminuria. Moreover, higher urinary L-FABP was a risk factor for progression of diabetic nephropathy.