tbuckley/cabot-search huggingface dataset:
Visceral Fat and Cardiovascular Risk Factors in Chinese NIDDM Patients
Authors: Patricia J Anderson, Juliana C N Chan, Y L Chan, Brian Tomlinson, Robert P Young, Zoe S K Lee, Kenneth K C Lee, Constantine Metreweli, Clive S Cockram, Julian A J H Critchley
Journal: Diabetes Care (1997)

OBJECTIVE The interrelations between obesity, glucose intolerance, hypertension, dyslipidemia, and insulin resistance are well recognized. These relationships are of particular interest in Hong Kong's Chinese population, in whom increasing affluence has coincided with a marked increase in the prevalence of NIDDM. We designed a pilot study to examine the relationships between visceral fat and cardiovascular risk factors in Chinese NIDDM patients. RESEARCH DESIGN AND METHODS We studied 21 Chinese NIDDM patients whose visceral fat was quantified by magnetic resonance imaging. Cardiovascular risk factors including plasma lipids and 24-h ambulatory blood pressure (BP) were measured. In addition, insulin resistance was determined by a short insulin tolerance test (SITT). RESULTS Increased visceral adiposity was significantly correlated with plasma triglycerides (r = 0.63, P = 0.004), the total cholesterol/HDL cholesterol ratio (r = 0.61, P = 0.008), the urinary albumin/creatinine ratio (r = 0.49, P = 0.04), and decreased insulin sensitivity as measured by the SITT (r = 0.47, P = 0.03). When the data were analyzed by tertiles, increasing visceral fat area was associated with higher plasma triglycerides, lower HDL cholesterol, and a smaller plasma glucose decrement during the SITT. In addition, the diurnal rhythm in BP and heart rate tended to be best preserved in those with the least visceral obesity. CONCLUSIONS This pilot study demonstrates that visceral fat accumulation is associated with dyslipidemia, hypertension, insulin resistance, and albuminuria in Chinese patients with NIDDM.
Safety, tolerability, pharmacokinetics, pharmacodynamics and efficacy of the monoclonal antibody ASK8007 blocking osteopontin in patients with rheumatoid arthritis: a randomised, placebo controlled, proof-of-concept study
Authors: M J H Boumans, J G A Houbiers, P Verschueren, H Ishikura, R Westhovens, E Brouwer, B Rojkovich, S Kelly, M den Adel, J Isaacs, H Jacobs, J Gomez-Reino, G M Holtkamp, A Hastings, D M Gerlag, P P Tak
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Objectives</h3> Osteopontin is an extracellular matrix protein with diverse immunomodulatory functions. The authors assessed the safety, tolerability, pharmacokinetics, pharmacodynamics and initial efficacy of the humanised monoclonal antibody ASK8007, which blocks osteopontin. <h3>Methods</h3> In this double-blind, multicentre, combined first-in-man, single-dose escalation (phase I, part A) and proof-of-concept, multiple-dose (phase IIA, part B) study, rheumatoid arthritis (RA) patients with active disease were randomly assigned to receive ASK8007 or placebo intravenously. Safety monitoring, pharmacokinetic and pharmacodynamic analyses and clinical assessments were performed throughout the study. The expression of phenotypic cell markers was evaluated in synovial tissue biopsy samples obtained at baseline and 43 days after initiation of treatment (part B) by immunohistochemistry and digital image analysis. Two co-primary efficacy endpoints were the change from baseline in the disease activity score evaluated in 28 joints (DAS28) and the change from baseline in the number of CD68 synovial sublining macrophages, both assessed on day 43 (part B). <h3>Results</h3> ASK8007 was overall safe and well tolerated up to the highest studied dose (20 mg/kg). Quantifiable concentrations of ASK8007 were detected in synovial fluid. No differences were observed for changes from baseline in DAS28 and CD68 sublining macrophages between ASK8007 and placebo-treated patients. Within the ASK8007 treatment group, there were also no apparent clinical responses or changes in sublining macrophages. In addition, ASK8007 treatment did not change other assessed biomarkers. <h3>Conclusions</h3> Osteopontin blockade is well tolerated and not related to safety concerns. These results consistently show that osteopontin blockade is unlikely to induce robust clinical improvement in RA patients.
Use of Lucozade and glucagon by ambulance staff in hypoglycaemia.
Authors: K. Jones, H. Stevens, D. Moody-Jones
Journal: BMJ (1992)

Outcome of excision of natal cleft sinus and primary closure compared with that of excision and secondary healing.Figures are medians (ranges) Primary closure Secondary Success Failure healing (n= 17) (n=6) (n=23) Days in hospital I (0)* 1 (1-2)* 3 (2-3) (day case) Days to healing 14 (0)* 37 5(26-48)t 41(29-51) (removal of sutures) Days off work 17 (15-21)* 38-5 (28-49)t 42 (28-56) Outpatient visits 2 (0)* 5-5 (4-6)t 6 (4-7) Visits by district nurse 0* 3 (2-5)t 4 (4-6)
Sex Differences in Survival of Oxygen-dependent Patients with Chronic Obstructive Pulmonary Disease
Authors: Maria-Christina L. Machado, Jerry A. Krishnan, Sonia A. Buist, Andrew L. Bilderback, Guilherme P. Fazolo, Michelle G. Santarosa, Fernando Queiroga, William M. Vollmer
Journal: American Journal of Respiratory and Critical Care Medicine (2006)

Section:ChooseTop of pageAbstract <<METHODSRESULTSDISCUSSIONCONCLUSIONSReferencesCITING ARTICLES
Diabetic Autonomic Neuropathy Affects Symptom Generation and Brain-Gut Axis
Authors: Christina Brock, Eirik Søfteland, Veronica Gunterberg, Jens Brøndum Frøkjær, Dina Lelic, Birgitte Brock, Georg Dimcevski, Hans Gregersen, Magnus Simrén, Asbjørn Mohr Drewes
Journal: Diabetes Care (2013)

OBJECTIVE Long-term diabetes leads to severe peripheral, autonomous, and central neuropathy in combination with clinical gastrointestinal symptoms. The brain-gut axis thus expresses a neurophysiological profile, and heart rate variability (HRV) can be correlated with clinical gastrointestinal symptoms. RESEARCH DESIGN AND METHODS Fifteen healthy volunteers and 15 diabetic patients (12 with type 1 diabetes) with severe gastrointestinal symptoms and clinical suspicion of autonomic neuropathy were included. Psychophysics and evoked brain potentials were assessed after painful rectosigmoid electrostimulations, and brain activity was modeled by brain electrical source analysis. Self-reported gastrointestinal symptoms (per the Patient Assessment of Upper Gastrointestinal Disorder Severity Symptom Index) and quality of life (SF-36 Short Form Survey) were collected. RESULTS Diabetic patients had autonomous neuropathy, evidenced by decreased electrocardiographic R-R interval (P = 0.03) and lower HRV (P = 0.008). Patients were less sensitive to painful stimulation (P = 0.007), had prolonged latencies of evoked potentials (P ≤ 0.001), and showed diminished amplitude of the N2–P2 component in evoked potentials (P = 0.01). There was a caudoanterior shift of the insular brain source (P = 0.01) and an anterior shift of the cingulate generator (P = 0.01). Insular source location was associated with HRV assessments (all P &amp;lt; 0.02), and the shift (expressed in mm) correlated negatively with physical health (P &amp;lt; 0.001) and positively with nausea (P = 0.03) and postprandial fullness (P = 0.03). Cingulate source shift was correlated negatively with physical health (P = 0.005) and positively with postprandial fullness (P ≤ 0.001). CONCLUSIONS This study provides evidence for interaction between autonomic neuropathy and peripheral nervous degeneration, as well as changes in dipole sources in diabetic patients with gastrointestinal symptoms. The findings may lead to improved treatment modalities targeting pharmacological neuroprotection or neuromodulation.
PPARs in atherosclerosis: the clot thickens
Authors: Antonio Castrillo, Peter Tontonoz
Journal: Journal of Clinical Investigation (2004)

Cardiovascular disease is the leading cause of morbidity and mortality in Western countries. Previous studies have highlighted the beneficial effects of PPARgamma activators on cardiovascular disease; however, the role of other PPAR family members in atherosclerosis is less clear. A report in this issue of the JCI expands our understanding of PPARs in vascular biology and highlights the potential use of multiple PPAR agonists to limit lipid accumulation in macrophages.
Computed tomography-quantified emphysema distribution is associated with lung function decline
Authors: Firdaus A.A. Mohamed Hoesein, Eva van Rikxoort, Bram van Ginneken, Pim A. de Jong, Mathias Prokop, Jan-Willem J. Lammers, Pieter Zanen
Journal: European Respiratory Journal (2012)

Emphysema distribution is associated with chronic obstructive pulmonary disease. It is, however, unknown whether computed tomography (CT)-quantified emphysema distribution (upper/lower lobe) is associated with lung function decline in heavy (former) smokers. 587 male participants underwent lung CT and pulmonary function testing at baseline and after a median (interquartile range) follow-up of 2.9 (2.8–3.0) yrs. The lungs were automatically segmented based on anatomically defined lung lobes. Severity of emphysema was automatically quantified per anatomical lung lobe and was expressed as the 15th percentile (Hounsfield unit point below which 15% of the low-attenuation voxels are distributed (Perc15)). The CT-quantified emphysema distribution was based on principal component analysis. Linear mixed models were used to assess the association of emphysema distribution with forced expiratory volume in 1 s (FEV 1 )/forced vital capacity (FVC), FEV 1 and FVC decline. Mean± sd age was 60.2±5.4 yrs, mean baseline FEV 1 /FVC was 71.6±9.0% and overall mean Perc15 was -908.5±20.9 HU. Participants with upper lobe-predominant CT-quantified emphysema had a lower FEV 1 /FVC, FEV 1 and FVC after follow-up compared with participants with lower lobe-predominant CT-quantified emphysema (p=0.001), independent of the total extent of CT-quantified emphysema. Heavy (former) smokers with upper lobe-predominant CT-quantified emphysema have a more rapid decrease in lung function than those with lower lobe-predominant CT-quantified emphysema.
Analysis of secondary pauses following termination of rapid atrial pacing in man.
Authors: D G Benditt, H C Strauss, M M Scheinman, V S Behar, A G Wallace
Journal: Circulation (1976)

The first ten cycles following cessation of atrial pacing were evaluated in 44 control subjects (mean age 52.9 +/- 14.88 yr) and 39 patients (mean age 62.9 +/- 15.41 yr) suspected of having sinus node dysfunction (SND). The maximal cycle length for each postpacing cycle following several pacing periods in each control subject was determined, and was normalized by dividing it by the subject's mean spontaneous control cycle length (SCL). Using the control group, a normalized maximal post-pacing response pattern (mean and SD) was derived. For each SND patient, a composite SD for each post-pacing cycle was calculated by adding the patient's SCL variance to the variance determined for each post-pacing cycle in the control group. Two composite SD above the mean value for each post-pacing cycle was selected as the upper limit of the normal recovery response and used to identify abnormal post-pacing responses in the 39 SND patients. Abnormally prolonged cycle lengths subsequent to the first escape cycle (secondary pauses) were found in 16/39 (41.0%) patients, of whom 11/39 (28.2%) had a prolonged SNRTmax. Of importance, 11/12 (91;7%) patients with documented SA block or sinus pauses prior to electrophysiologic study, demonstrated secondary pauses, while only 7/12 (58.3%) had a prolonged SNRTmax. Criteria are derived for the identification of secondary pauses during the postpacing period, and a close association between secondary pauses and the presence of spontaneous SA block or sinus pauses prior to electrophysiologic study is demonstrated.
Prevalence of Marijuana Use Disorders in the United States Between 2001-2002 and 2012-2013
Authors: Deborah S. Hasin, Tulshi D. Saha, Bradley T. Kerridge, Risë B. Goldstein, S. Patricia Chou, Haitao Zhang, Jeesun Jung, Roger P. Pickering, W. June Ruan, Sharon M. Smith, Boji Huang, Bridget F. Grant
Journal: JAMA Psychiatry (2015)

Laws and attitudes toward marijuana in the United States are becoming more permissive but little is known about whether the prevalence rates of marijuana use and marijuana use disorders have changed in the 21st century.To present nationally representative information on the past-year prevalence rates of marijuana use, marijuana use disorder, and marijuana use disorder among marijuana users in the US adult general population and whether this has changed between 2001-2002 and 2012-2013.Face-to-face interviews conducted in surveys of 2 nationally representative samples of US adults: the National Epidemiologic Survey on Alcohol and Related Conditions (data collected April 2001-April 2002; N = 43,093) and the National Epidemiologic Survey on Alcohol and Related Conditions-III (data collected April 2012-June 2013; N = 36,309). Data were analyzed March through May 2015.Past-year marijuana use and DSM-IV marijuana use disorder (abuse or dependence).The past-year prevalence of marijuana use was 4.1% (SE, 0.15) in 2001-2002 and 9.5% (SE, 0.27) in 2012-2013, a significant increase (P < .05). Significant increases were also found across demographic subgroups (sex, age, race/ethnicity, education, marital status, income, urban/rural, and region). The past-year prevalence of DSM-IV marijuana use disorder was 1.5% (0.08) in 2001-2002 and 2.9% (SE, 0.13) in 2012-2013 (P < .05). With few exceptions, increases in the prevalence of marijuana use disorder between 2001-2002 and 2012-2013 were also statistically significant (P < .05) across demographic subgroups. However, the prevalence of marijuana use disorder among marijuana users decreased significantly from 2001-2002 (35.6%; SE, 1.37) to 2012-2013 (30.6%; SE, 1.04).The prevalence of marijuana use more than doubled between 2001-2002 and 2012-2013, and there was a large increase in marijuana use disorders during that time. While not all marijuana users experience problems, nearly 3 of 10 marijuana users manifested a marijuana use disorder in 2012-2013. Because the risk for marijuana use disorder did not increase among users, the increase in prevalence of marijuana use disorder is owing to an increase in prevalence of users in the US adult population. Given changing laws and attitudes toward marijuana, a balanced presentation of the likelihood of adverse consequences of marijuana use to policy makers, professionals, and the public is needed.
Renin and Acute Circulatory Renal Failure in the Rabbit
Authors: WILLIAM C.B. BROWN, JEHOIDA J. BROWN, HARALAMBOS GAVRAS, ALAN JACKSON, ANTHONY F. LEVER, JAMES MCGREGOR, ROBERT F. MACADAM, J.IAN S. ROBERTSON
Journal: Circulation Research (1972)

Plasma renin concentration (PRC) was measured in 25 rabbits before and 6, 24, or 72 hours after subcutaneous injection of glycerol. Renal failure and tubular necrosis developed in most animals and PRC rose sixfold to a maximum at 24 hours. Small insignificant changes of PRC were present at 6 and 72 hours. None of these changes was observed in a control group of nine animals killed 24 hours after an injection of saline. The amount of renin extractable from single superficial glomeruli and from renal cortical tissue was reduced after injection of glycerol. In a second study of 11 anesthetized rabbits, renal venous PRC increased on average from 151 to 1810 units/liter following a 4-hour period of renal artery occlusion. Arterial PRC did not change significantly during this time, but the kidneys showed histological changes of acute tubular necrosis. These experiments are compatible with the suggestion that renin is involved in the pathogenesis of acute circulatory renal failure.
Array-Based DNA Diagnostics: Let the Revolution Begin
Authors: Arthur L. Beaudet, John W. Belmont
Journal: Annual Review of Medicine (2007)

Advances in the fabrication of DNA microarrays as well as transformations in detection chemistries have vastly increased the throughput for genotyping, DNA sequencing, and array-based copy number analysis (ABCNA). Rapid changes in technology are not only affecting research but also revolutionizing DNA diagnostics. Here we focus on the application of high-throughput ABCNA and genotyping. Targeted and genome-wide ABCNA has led to the discovery of extensive DNA copy number variation in the population and the delineation of many previously unrecognized submicroscopic chromosomal aberrations (genomic disorders). High-throughput single-nucleotide polymorphism (SNP) genotyping is being widely applied in genome-wide association studies (GWASs) with recent successes in identification of common variants that confer risk for common adult diseases. Future applications of high-throughput genotyping and array-based DNA sequencing technology will undoubtedly involve research and diagnostic analyses of rare mutations and perhaps ultimately enable full individual genome sequencing.
Correlation between transmural high energy phosphate levels and myocardial blood flow in the presence of graded coronary stenosis.
Authors: G Path, P M Robitaille, H Merkle, M Tristani, J Zhang, M Garwood, A H From, R J Bache, K Uğurbil
Journal: Circulation Research (1990)

Spatially localized nuclear magnetic resonance spectroscopy was used to investigate with transmural differentiation the response of myocardial high energy phosphate compounds and inorganic orthophosphate (Pi) to graded reductions in coronary blood flow caused by sustained coronary stenosis. In an open-chest model, localized 31P nuclear magnetic resonance spectra from five layers across the left ventricular wall were obtained simultaneously with transmural blood flow measurements during control conditions and during sustained graded reductions in intracoronary pressure. Both the blood flow, and high energy phosphate and Pi contents displayed transmural heterogeneity in response to decreases in intracoronary pressure. The subendocardial creatine phosphate (CP) level remained unchanged as blood flow was reduced to approximately 0.7 ml/min/g wet wt and decreased precipitously beyond this critical flow level. The relation between CP and flow in the midmyocardium and especially in the subepicardium was more complex. Subepicardial CP content did not correlate well with blood flow; however, in cases in which a coronary stenosis resulted in subendocardial hypoperfusion but subepicardial flow was near or above normal, a close correlation was present between subepicardial and subendocardial CP levels. ATP levels in all layers remained unaltered until blood flow was severely reduced. These results demonstrate that 1) the myocardial high energy phosphate and Pi levels at any transmural layer are not generally determined by O2 and blood flow limitation under basal conditions; 2) during subtotal coronary occlusion, increased oxygen extraction is able to meet myocardial needs until a critical level of stenosis is reached; 3) below a critical flow level, subendocardial CP and Pi contents are closely correlated with absolute subendocardial blood flow; and 4) in the presence of a coronary stenosis, subepicardial CP and Pi contents may change even in the absence of perfusion deficit secondary to loss of subendocardial function.
Abstract 417: DNA methylation changes in Lynch syndrome and FAP-associated colorectal tumorigenesis
Authors: Satu Valo, Sippy Kaur, Ari Ristimäki, Laura Renkonen-Sinisalo, Heikki Järvinen, Jukka-Pekka Mecklin, Minna Nyström, Päivi Peltomäki
Journal: Cancer Research (2014)

Abstract Colorectal cancer (CRC) develops via multiple steps which involve genetic changes, such as mutations in growth-regulatory genes, and epigenetic alterations, such as CpG island hypermethylation. These changes accumulate over time in the normal tissue, for example due to many environmental factors such as diet, and may result in pre-cancerous field defects. Genes having high level of methylation in peritumoral tissues could be used as biomarkers for colorectal carcinogenesis. The most common familial cancer susceptibility syndromes are familial adenomatous polyposis (FAP), caused by inherited mutations in the APC tumor suppressor gene, and Lynch syndrome (LS), associated with inherited defects of the DNA mismatch repair (MMR) genes which together with other genetic and epigenetic changes are known to accelerate tumorigenesis. This investigation was designed to define how CpG island methylation of CRC risk genes varies in pre-cancerous and cancerous lesions, adjacent normal mucosa and distinct normal mucosa from genetically predisposed individuals. Colonic mucosa biopsies from different colorectal regions were gathered from 40 Finnish LS mutation carriers and 23 FAP patients during regular surveillance. In addition with normal mucosa biopsies, all adenoma and carcinoma findings from these individuals together with matching normals were gathered and analyzed. Patient information was obtained from the nation-wide registry. CpG island methylation was studied with the methylation-specific multiplex ligation-dependent probe amplification test (MS-MLPA) which detects CpG methylation of selected genes. Immunohistochemistry was used to detect MMR protein expression in neoplastic lesions. Of 16 CRC risk genes tested so far 9 show increased methylation in polyps/adenomas/carcinomas. Mean methylation values increase along with age in both syndromes, with polyps from LS showing the highest proportional increase relative to normal tissues. The results offer new insights to the molecular mechanisms through which DNA methylation can affect colorectal carcinogenesis in LS and FAP mutation carriers. Citation Format: Satu Valo, Sippy Kaur, Ari Ristimäki, Laura Renkonen-Sinisalo, Heikki Järvinen, Jukka-Pekka Mecklin, Minna Nyström, Päivi Peltomäki. DNA methylation changes in Lynch syndrome and FAP-associated colorectal tumorigenesis. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 417. doi:10.1158/1538-7445.AM2014-417
Vemurafenib skin phototoxicity is indirectly linked to ultraviolet A minimal erythema dose decrease
Authors: C. Brugière, A. Stefan, C. Morice, E. Cornet, A. Moreau, S. Allouche, L. Verneuil
Journal: British Journal of Dermatology (2014)

Vemurafenib, an anti-rapidly accelerated fibrosarcoma kinase B (BRAF) molecule, improves survival among patients with metastatic BRAF-mutated melanoma. Photosensitivity, a frequent cutaneous adverse effect induced by vemurafenib, can lead to cessation of treatment.To investigate photosensitivity mechanisms in patients treated with vemurafenib for metastatic melanoma.In a prospective study of 12 patients, photobiological explorations with measurements of ultraviolet A (UVA) minimal erythema dose (MED) and polychromatic MED were performed over 3 days in all 12 patients. UVA MED and polychromatic MED were also assessed for four patients before treatment. We then performed spectrophotometric analyses of (i) serum and faeces in these four patients, before and after introduction of vemurafenib; (ii) the lyophilized form of vemurafenib without excipient added; and (iii) the lyophilized form of vemurafenib added to serum and faeces before treatment.Photosensitivity was present in 92% of the patients. UVA MED was normal before treatment and decreased after treatment, while polychromatic MED remained normal. The same three peaks (210, 260 and 310 nm) were identified in the spectrum for UVB and UVC but not for UVA on spectrophotometric analyses for each condition (lyophilized vemurafenib; serum and faeces after introduction of vemurafenib; and lyophilized vemurafenib added to serum and faeces before treatment). The peaks were different before treatment.Our study confirms that photosensitivity under vemurafenib treatment was a UVA phototoxicity reaction, and our results suggest that a metabolite of vemurafenib rather than the parent molecule is involved in this phototoxicity.