tbuckley/cabot-search huggingface dataset:
Glucose Homeostasis and Genotype-Phenotype Interplay in Cystic Fibrosis Patients With CFTR Gene ΔF508 Mutation
Authors: Vanessa Preumont, Michel P. Hermans, Patrick Lebecque, Martin Buysschaert
Journal: Diabetes Care (2007)

We sought to determine the clinical phenotype of adolescent/adult patients with cystic fibrosis, according to heterozygosity or homozygosity for cystic fibrosis transmembrane regulator (CFTR) deltaF508 mutation, and to analyze their characteristics according to glucose tolerance status.A total of 76 cystic fibrosis patients with CFTR deltaF508 mutation (33 heterozygous and 43 homozygous) stratified according to normal glucose tolerance (NGT) (n = 51) or abnormal glucose homeostasis (AGH) (impaired fasting glucose, impaired glucose tolerance, or diabetes; n = 25) had their homeostasis model assessment (HOMA) of beta-cell function and of insulin sensitivity and hyperbolic product (beta-cell function x insulin sensitivity [B x S]) measured. Pancreatic exocrine insufficiency was inferred from pancreatine requirements. Clinical effects of insulin therapy on weight and lung function were recorded.AGH was observed in 24 and 40% of heterozygous and homozygous subjects, respectively. AGH patients were older than NGT patients (mean +/- SD age 29 +/- 10 vs. 23 +/- 8 years, P = 0.006), and their beta-cell function was lower (93 +/- 49 vs. 125 +/- 51%, P = 0.011). Insulin sensitivity values were comparable in NGT and AGH patients. A lower B x S product was observed in AGH, although it was nonsignificant when adjusted for error propagation. Pancreatic insufficiency was observed in 52 and 100% of heterozygous and homozygous patients (P = 0.001).Pre-diabetes and diabetes represent frequent comorbidities in CFTR deltaF508 mutation in the homozygous or heterozygous states. Impairment of insulin secretion, as shown by HOMA, is an important determinant when compared with the magnitude of compensation from insulin sensitivity. Given the high prevalence of abnormal glucose tolerance, screening for (pre-)diabetes is mandatory. Insulin supplementation in diabetic subjects with CFTR deltaF508 mutation seems a rational therapy for consideration, although this does not preclude that therapy directed toward insulin resistance could also interact.
Hemodynamics of Dogs in Histamine Shock, with Special Reference to Splanchnic Blood Volume and Flow
Authors: SHU CHIEN, LAWRENCE KRAKOFF
Journal: Circulation Research (1963)

After the subcutaneous injection of histamine (3 mg/kg), changes in splanchnic and systemic circulation were studied in splenectomized dogs under sodium pentobarbital. The estimated splanchnic blood flow (BSP clearance and extraction) decreased by 67%. The extent of the decrease was almost the same as that for the mean arterial pressure; thus the splanchnic vascular resistance remained unchanged. This unchanged splanchnic resistance was ascribed to a combination of arteriolar dilatation and hepatic venoconstriction, and the latter was indicated by the increase in the wedged hepatic venous pressure in the face of a decreased flow. The ciculating splanchnic blood volume (equilibration technique) was not significantly changed after histamine, but there was a decrease in the splanchnic cell percentage. Therefore, the evidence indicates that during histamine shock there was a shift of blood from the hepatic veins to the capillaries, rather than a pooling of blood in the splanchnic circulation. The decrease in the splanchnic cell percentage was about the same as the decrease in the overall cell percentage. The venoconstriction in the hepatic circulation and probably also that in the other circuits contributed to a reduction in venous return. The cardiac output (indicator dilution method) decreased by an average of 51%. The total peripheral resistance decreased by an average of 39%. The drastic and persistent arterial hypotension in histamine shock was due to decreases in both the cardiac output and the peripheral resistance.
International Expert Panel on the Use of Primary (Preoperative) Systemic Treatment of Operable Breast Cancer: Review and Recommendations
Authors: Manfred Kaufmann, Gunter von Minckwitz, Roy Smith, Vicente Valero, Luca Gianni, Wolfgang Eiermann, Anthony Howell, Serban Dan Costa, Philippe Beuzeboc, Michael Untch, Jens-Uwe Blohmer, Hans-Peter Sinn, Rolf Sittek, Rainer Souchon, Augustinos H. Tulusan, Tanja Volm, Hans-Jörg Senn
Journal: Journal of Clinical Oncology (2003)

Primary systemic therapy (PST) represents the standard of care in patients with locally advanced breast cancer. In addition, there is increasing information on PST in operable breast disease that supports the use of PST in routine practice. However, current regimens and techniques vary. To address this concern, a group of representatives from breast cancer clinical research groups in France, Germany, Italy, the United Kingdom, and the United States reviewed all available data on prospective randomized trials in this setting. Recommendations are made regarding terminology, indications, regimen, diagnosis before treatment, monitoring of efficacy, tumor localization, surgery, pathologic evaluation, and postoperative treatment.
Diagnosing Diabetes With Glucose Criteria: Worshipping a False God
Authors: Mayer B. Davidson
Journal: Diabetes Care (2011)

In this issue of Diabetes Care , Dr. David Sacks has nicely delineated the pros and cons of the measurements of glucose concentrations and A1C levels and the resulting effects on using each to diagnose diabetes (1). With the continued improvement in A1C assays, the balance seems to increasingly favor using A1C levels. This commentary will examine an issue that has received scant attention in the past, i.e., what is the actual evidence upon which the current glucose criteria for diagnosing diabetes mellitus is based?

Glucose concentrations in almost all populations (except those with very high prevalences of diabetes, e,g., Pima Indians), are distributed unimodally with a rightward skew (2,3), making the choice of a diagnostic value for diabetes arbitrary. If glucose concentrations are log-transformed to minimize the rightward skewness, a bimodal distribution has been noted (4–8). However, cutoff values defining the two distributions have ranged from 200–307 mg/dL, mostly depending on the ages of the population surveyed (3–8).

Prior to 1979, at least six different sets of criteria diagnosed diabetes (9). In 1979, the National Diabetes Data Group (NDDG) resolved this issue by establishing one set of criteria (10). They selected these criteria based on glucose concentrations that allegedly predicted the development of diabetic retinopathy, a specific microvascular complication of diabetes. Three prospective studies (11–13) were available to the NDDG on which to base their decision. A total of 1,213 patients were followed for 3 to 8 years after oral glucose tolerance tests (OGTTs), 77 of whom developed retinopathy. There was no further evaluation of their glycemic status after the original OGTT, although it was very likely that the 77 people who developed retinopathy in the studies used by the NDDG to establish the diagnostic criteria had increasing glycemia in …
Radiotherapy with or without Chemotherapy in Muscle-Invasive Bladder Cancer
Authors: Nicholas D. James, Syed A. Hussain, Emma Hall, Peter Jenkins, Jean Tremlett, Christine Rawlings, Malcolm Crundwell, Bruce Sizer, Thiagarajan Sreenivasan, Carey Hendron, Rebecca Lewis, Rachel Waters, Robert A. Huddart
Journal: New England Journal of Medicine (2012)

Radiotherapy is an alternative to cystectomy in patients with muscle-invasive bladder cancer. In other disease sites, synchronous chemoradiotherapy has been associated with increased local control and improved survival, as compared with radiotherapy alone.
Relationship of vitamin D with insulin resistance and disease severity in non-alcoholic steatohepatitis
Authors: Fernando Bril, Maryann Maximos, Paola Portillo-Sanchez, Diane Biernacki, Romina Lomonaco, Sreevidya Subbarayan, Mark Correa, Margaret Lo, Amitabh Suman, Kenneth Cusi
Journal: Journal of Hepatology (2014)
Rituximab (anti-CD20 monoclonal antibody) for the treatment of patients with clonal lymphoproliferative disorders after orthotopic liver transplantation: a report of three cases
Authors: Simona Zompi, Micheline Tulliez, Filoména Conti, Véronique Leblond, Philippe Gaulard, Philippe Blanche, François Durand, Damaj Ghandi, François Dreyfus, Albert Louvel, Yvon Calmus, Didier Bouscary
Journal: Journal of Hepatology (2000)
Inhaled corticosteroids and survival in chronic obstructive pulmonary disease
Authors: J. Bourbeau
Journal: European Respiratory Journal (2003)

The reciprocals of the blood urea nitrogen and plasma creatinine levels, the maximum specific gravity of the urine after vasopressin, and three modified forms of the phenolsulphonphthalein (P.S.P.) excretion test were found to be directly related to the glomerular filtration rate (G.F.R.) in hospital patients. From 34 to 75 patients were studied for each test, and in 21 patients all tests were performed concurrently. The plasma creatinine level and the 15-minute urinary excretion of P.S.P. were found to be the most useful simple tests of renal function and gave sufficiently accurate estimates of total function (G.F.R.) to justify their more extensive use. The G.F.R. (ml./min./1·73 sq. m. of body surface area) could be calculated from each test, using the following equations:— [Formula: see text] G.F.R. = 3·15 × P.S.P.% + 19, where P.S.P.% is the 15-minute urinary excretion of P.S.P., expressed as a percentage of the administered dose. Satisfactory estimates of G.F.R. were also given by the simplified relationships [Formula: see text]. In the presence of impaired renal function more accurate estimates of G.F.R. were obtained from the plasma creatinine and P.S.P. excretion tests (S.D. of estimate 8 and 13 ml./min. respectively). It was thought that these tests could well replace the commonly used blood urea nitrogen estimation as simple tests of renal function.
NITRIC OXIDE SYNTHASE: Role as a Transmitter/Mediator in the Brain and Endocrine System
Authors: Ted M. Dawson, M.D., Ph.D, Valina L. Dawson, Ph.D
Journal: Annual Review of Medicine (1996)

▪ Abstract Nitric oxide is a unique biological messenger molecule. It is produced by endothelial cells to mediate blood vessel relaxation; it mediates, in part, the immune functions of activated macrophages; and in the central and peripheral nervous system it serves as a neurotransmitter. In the nervous system, nitric oxide may regulate neurotransmitter release, it may play a key role in synaptic plasticity and morphogenesis, and it may regulate sexual and aggressive behavior. Under conditions of excessive formation, nitric oxide is emerging as an important neurotoxin.
Profound adrenal suppression secondary to treatment with low dose inhaled steroids and itraconazole in allergic bronchopulmonary aspergillosis in cystic fibrosis
Authors: J S Parmar
Journal: Thorax (2002)

This study describes small bowel push enteroscopy in routine clinical practice, using a purpose designed instrument (Olympus SIF-10). Fifty six patients had a total of 60 procedures over a two and a half year period. The median (range) depth of small intestine intubated was 45 (15-90) cm. Procedure time varied from 10-45 minutes. Most enteroscopies were performed during routine gastroscopy lists. The technique was comparatively easy for experienced endoscopists to learn. Forty two procedures were for diagnostic purposes. Eleven patients had gastrointestinal bleeding where the source was obscure, or where early investigations had suggested a small bowel source: a specific diagnosis was made in 45% of these cases. Of seven iron deficient anaemic patients using non-steroidal anti-inflammatory drugs (NSAIDs), only one had a lesion detected in the upper small bowel. Nine patients had abnormal small bowel barium studies. Small bowel abnormalities were seen in six cases and were definitively diagnostic in three of these; in three patients the barium study appearances were confirmed as artefact. Fifteen patients were investigated for abdominal symptoms suggesting small bowel obstruction or malabsorption: a diagnosis was made in five cases. Fifteen patients underwent enteroscopy for therapeutic purposes, including successful treatment of difficult enteral feeding problems by nasojejunal tubes or by cutaneous endoscopic jejunostomies, polypectomy for Peutz-Jeghers syndrome, and dilatation of strictures. Additionally, bleeding lesions detected in patients during investigation of anaemia were successfully treated at the time by YAG laser or bipolar diathermy. In conclusion, push enteroscopy is a practical and valuable clinical service, which should probably become available on a subregional basis.
Risks of Intracranial Hemorrhage Among Patients With Acute Ischemic Stroke Receiving Warfarin and Treated With Intravenous Tissue Plasminogen Activator
Authors: Ying Xian, Li Liang, Eric E Smith, Lee H Schwamm, Mathew J Reeves, DaiWai M Olson, Adrian F Hernandez, Gregg C Fonarow, Eric D Peterson
Journal: JAMA (2012)

<h3>Context</h3>Intravenous tissue plasminogen activator (tPA) is known to improve outcomes in ischemic stroke; however, patients receiving long-term chronic warfarin therapy may face an increased risk for intracranial hemorrhage when treated with tPA. Although current guidelines endorse administering intravenous tPA to warfarin-treated patients if their international normalized ratio (INR) is 1.7 or lower, there are few data on safety of intravenous tPA in warfarin-treated patients in clinical practice.<h3>Objectives</h3>To determine the risk of symptomatic intracranial hemorrhage (sICH) among patients with ischemic stroke treated with intravenous tPA who were receiving warfarin vs those who were not and to determine this risk as a function of INR.<h3>Design, Setting, and Patients</h3>Observational study, using data from the American Heart Association Get With The Guidelines–Stroke Registry, of 23 437 patients with ischemic stroke and with INR of 1.7 or lower, treated with intravenous tPA in 1203 registry hospitals from April 2009 through June 2011.<h3>Main Outcome Measure</h3>Symptomatic intracranial hemorrhage. Secondary end points include life-threatening/serious systemic hemorrhage, any tPA complications, and in-hospital mortality.<h3>Results</h3>Overall, 1802 (7.7%) patients with stroke treated with tPA were receiving warfarin (median INR, 1.20; interquartile range [IQR], 1.07-1.40). Warfarin-treated patients were older, had more comorbid conditions, and had more severe strokes. The unadjusted sICH rate in warfarin-treated patients was higher than in non–warfarin-treated patients (5.7% vs 4.6%, P &lt; .001), but these differences were not significantly different after adjustment for baseline clinical factors (adjusted odds ratio [OR], 1.01 [95% CI, 0.82-1.25]). Similarly, there were no significant differences between warfarin-treated and non–warfarin-treated patients for serious systemic hemorrhage (0.9% vs 0.9%; adjusted OR, 0.78 [95% CI, 0.49-1.24]), any tPA complications (10.6% vs 8.4%; adjusted OR, 1.09 [95% CI, 0.93-1.29]), or in-hospital mortality (11.4% vs 7.9%; adjusted OR, 0.94 [95% CI, 0.79-1.13]). Among warfarin-treated patients with INRs of 1.7 or lower, the degree of anticoagulation was not statistically significantly associated with sICH risk (adjusted OR, 1.10 per 0.1-unit increase in INR [95% CI, 1.00-1.20]; P = .06).<h3>Conclusion</h3>Among patients with ischemic stroke, the use of intravenous tPA among warfarin-treated patients (INR ≤1.7) was not associated with increased sICH risk compared with non–warfarin-treated patients.
Assessing the Prognostic Value of Cardiovascular Imaging
Authors: Rory Hachamovitch
Journal: Circulation (2009)

C ardiovascular imaging has become the focus of attention from both physicians and payers.The former see the potential of newer modalities to permit new and exciting insights into the diagnosis and management of coronary artery disease (CAD), that, in turn, may result in enhanced patient care strategies and new efficient clinical algorithms.On the other hand, payers have understandable concerns about the excessive use and enormous costs associated with cardiovascular imaging.These concerns have been exacerbated by the rapid expansion of the imaging devices used for the assessment of patients with known or suspected CAD.Cardiovascular stress imaging has long been the domain of stress single photon emission computed tomography myocardial perfusion imaging (SPECT MPI) and stress echocardiography wall motion studies.At present, stress positron emission tomography (PET) MPI, cardiac computed tomography coronary angiography (CTA) (and, possibly, stress CT MPI), as well as cardiac magnetic resonance imaging (CMR) MPI and wall motion studies are utilized in daily practice.Whether all of these modalities will be reimbursed in the future is uncertain, but little doubt remains that their rigorous validation will be compulsory.
MiR-124 suppresses tumor growth and metastasis by targeting Foxq1 in nasopharyngeal carcinoma
Authors: Xiao Hong Peng, Hao Ran Huang, Juan Lu, Xiong Liu, Fei Peng Zhao, Bao Zhang, Shao Xiong Lin, Lu Wang, Huai Hong Chen, Xia Xu, Fan Wang, Xiang Ping Li
Journal: Molecular Cancer (2014)

The molecular mechanisms underlying dysregulation of microRNAs have been documented in nasopharyngeal carcinoma (NPC). Our previous study demonstrated that plasma miR-124 was down-regulated in NPC using microarray analysis and quantitative PCR validation. Though growing studies showed that down-regulated miR-124 was closely related to tumourigenesis in various types of cancers, the role of miR-124 in NPC remains largely unknown. The expression level of miR-124 was evaluated in NPC cell lines and patient specimens using quantitative reverse transcription-PCR (Real-time qPCR). The clinicopathological significance of the resultant data was later analyzed. Then, we explored the role of miR-124 in NPC tumorigenesis by in vitro and in vivo experiments. Homo sapiens forkhead box Q1 (Foxq1) was confirmed as a novel direct target gene of miR-124 by the dual-luciferase assay and western bolt. We found that miR-124 was commonly down-regulated in NPC specimens and NPC cell lines. The expression of miR-124 was inversely correlation with clinical stages and marked on T stages. Then, the ectopic expression of miR-124 dramatically inhibited cell proliferation, colony formation, migration and invasion in vitro, as well as tumor growth and metastasis in vivo. Furthermore, we identified Foxq1 as a novel direct target of miR-124. Functional studies showed that knockdown of Foxq1 inhibited cell growth, migration and invasion, whereas Foxq1 overexpression partially rescued the suppressive effect of miR-124 in NPC. In clinical specimens, Foxq1 was commonly up-regulated in NPC, and the level increased with clinical stages and T stages. Additionally, the level of Foxq1 was inversely correlated with miR-124. Our results demonstrate that miR-124 functions as a tumor-suppressive microRNA in NPC, and that its suppressive effects are mediated chiefly by repressing Foxq1 expression. MiR-124 could serve as an independent biomarker to identify patients with different clinical characteristics. Therefore, our findings provide valuable clues toward the understanding the of mechanisms of NPC pathogenesis and provide an opportunity to develop new effective clinical therapies in the future.
Prediction of Diabetes Based on Baseline Metabolic Characteristics in Individuals at High Risk
Authors: Ralph A. DeFronzo, Devjit Tripathy, Dawn C. Schwenke, MaryAnn Banerji, George A. Bray, Thomas A. Buchanan, Stephen C. Clement, Robert R. Henry, Abbas E. Kitabchi, Sunder Mudaliar, Robert E. Ratner, Frankie B. Stentz, Nicolas Musi, Peter D. Reaven, Amalia Gastaldelli
Journal: Diabetes Care (2013)

Individuals with impaired glucose tolerance (IGT) are at high risk for developing type 2 diabetes mellitus (T2DM). We examined which characteristics at baseline predicted the development of T2DM versus maintenance of IGT or conversion to normal glucose tolerance.We studied 228 subjects at high risk with IGT who received treatment with placebo in ACT NOW and who underwent baseline anthropometric measures and oral glucose tolerance test (OGTT) at baseline and after a mean follow-up of 2.4 years.In a univariate analysis, 45 of 228 (19.7%) IGT individuals developed diabetes. After adjusting for age, sex, and center, increased fasting plasma glucose, 2-h plasma glucose, G0-120 during OGTT, HbA1c, adipocyte insulin resistance index, ln fasting plasma insulin, and ln I0-120, as well as family history of diabetes and presence of metabolic syndrome, were associated with increased risk of diabetes. At baseline, higher insulin secretion (ln [I0-120/G0-120]) during the OGTT was associated with decreased risk of diabetes. Higher β-cell function (insulin secretion/insulin resistance or disposition index; ln [I0-120/G0-120 × Matsuda index of insulin sensitivity]; odds ratio 0.11; P < 0.0001) was the variable most closely associated with reduced risk of diabetes.In a stepwise multiple-variable analysis, only HbA1c and β-cell function (ln insulin secretion/insulin resistance index) predicted the development of diabetes (r = 0.49; P < 0.0001).
Langerhans cell histiocytosis: Lack of a viral etiology
Authors: Kenneth McClain, Hong Jin, Vicky Gresik, Blaise Favara
Journal: American Journal of Hematology (1994)

Abstract Langerhans cell histiocytosis (LCH) is an enigmatic histiocytic proliferative disorder of unknown etiology that affects children primarily. We have investigated the possibility that viruses are etiological or that they have a “triggering effect” in LCH. Sensitive in situ hybridization and polymerase chain reaction (PCR) techniques were used in 56 cases of LCH. We sought and failed to find evidence of genomes for adenovirus, cytomegalovirus, Epstein‐Barr virus, herpes simplex virus, human herpesvirus type 6, human immunodeficiency virus, human T‐cell leukemia virus types I and II, and parvovfrus. Although some probes hybridized to tissues from several cases, PCR failed to confirm the presence of viral genome in any. We conclude that there is no evidence that these viruses are associated with LCH. © 1994 Wiley‐Liss, Inc.
Mechanisms of Visual Attention in the Human Cortex
Authors: Sabine Kastner and Leslie G. Ungerleider
Journal: Annual Review of Neuroscience (2000)

A typical scene contains many different objects that, because of the limited processing capacity of the visual system, compete for neural representation. The competition among multiple objects in visual cortex can be biased by both bottom-up sensory-driven mechanisms and top-down influences, such as selective attention. Functional brain imaging studies reveal that, both in the absence and in the presence of visual stimulation, biasing signals due to selective attention can modulate neural activity in visual cortex in several ways. Although the competition among stimuli for representation is ultimately resolved within visual cortex, the source of top-down biasing signals derives from a network of areas in frontal and parietal cortex.
Prospective Study of Diagnostic Accuracy Comparing Prostate Cancer Detection by Transrectal Ultrasound–Guided Biopsy Versus Magnetic Resonance (MR) Imaging with Subsequent MR-guided Biopsy in Men Without Previous Prostate Biopsies
Authors: Morgan R Pokorny, Maarten de Rooij, Earl Duncan, Fritz H Schröder, Robert Parkinson, Jelle O Barentsz, Leslie C Thompson
Journal: European Urology (2014)