tbuckley/cabot-search huggingface dataset:
Assessment of Diabetes Care by Medical Record Review: The Indian Health Service Model
Authors: Jennifer A Mayfield, Stephen J Rith-Najarean, Kelly J Acton, Cynthia D Schraer, Ruggles M Stahn, Mildred H Johnson, Dorothy Gohdes
Journal: Diabetes Care (1994)

OBJECTIVE To evaluate the adherence to minimum standards for diabetes care in multiple primary-care facilities using a uniform system of medical record review. RESEARCH DESIGN AND METHODS In 1986, the Indian Health Service (IHS) developed diabetes care standards and an assessment process to evaluate adherence to those standards using medical record review. We review our assessment method and results for 1992. Charts were selected in a systematic random fashion from 138 participating facilities. Trained professional stai reviewed patient charts, using a uniform set of definitions. A weighted rate of adherence was constructed for each item. RESULTS Medical record reviews were conducted on 6,959 charts selected from 40,118 diabetic patients. High rates of adherence (&amp;gt;70%) were noted for blood pressureand weight measurements at each visit, blood sugar determinations at each visit, annual laboratory screening tests, electrocardiogram at baseline, and adult immunizations. Lower rates of adherence (≤50%) were noted for annual eye, foot, and dental examinations. CONCLUSIONS IHS rates of adherence are similar to rates obtained from medical record reviews and computerized billing data, but are less than rates obtained by provider self-report. Medical record review, using uniform definitions and inexpensive software for data entry and reports, can easily be implemented in multiple primary-care settings. Uniformity of data definition and collection facilitates the aggregation of the data and comparison over time and among facilities. This medical record review system, although labor intensive, can be easily adopted in a variety of primary-care settings for quality improvement activities, program planning, and evaluation.
Effect of salbutamol on lung function and chest wall volumes at rest and during exercise in COPD
Authors: A Aliverti
Journal: Thorax (2005)

Inhaled bronchodilators can increase exercise capacity in chronic obstructive pulmonary disease (COPD) by reducing dynamic hyperinflation, but treatment is not always effective. This may reflect the degree to which the abdomen allows dynamic hyperinflation to occur.A double blind, randomised, crossover trial of the effect of 5 mg nebulised salbutamol or saline on endurance exercise time was conducted in 18 patients with COPD of mean (SD) age 67.1 (6.3) years and mean (SD) forced expiratory volume in 1 second (FEV1) of 40.6 (15.0)% predicted. Breathing pattern, metabolic variables, dyspnoea intensity, and total and regional chest wall volumes were measured non-invasively by optoelectronic plethysmography (OEP) at rest and during exercise.Salbutamol increased FEV1, forced vital capacity (FVC) and inspiratory capacity and reduced functional residual capacity (FRC) and residual volume significantly. OEP showed the change in resting FRC to be mainly in the abdominal compartment. Although the mean (SE) end expiratory chest wall volume was 541 (118) ml lower (p<0.001) at the end of exercise, the endurance time was unchanged by the bronchodilator. Changes in resting lung volumes were smaller when exercise duration did not improve, but FEV1 still rose significantly after active drug. After the bronchodilator these patients tried to reduce the end expiratory lung volume when exercising, while those exercising longer continued to allow end expiratory abdominal wall volume to rise. The change to a more euvolumic breathing pattern was associated with a lower oxygen pulse and a significant fall in endurance time with higher isotime levels of dyspnoea.Nebulised salbutamol improved forced expiratory flow in most patients with COPD, but less hyper-nflated patients tried to reduce the abdominal compartmental volume after active treatment and this reduced their exercise capacity. Identifying these patients has important therapeutic implications, as does an understanding of the mechanisms that control chest wall muscle recruitment.
Efficacy of antilipopolysaccharide and anti-tumor necrosis factor monoclonal antibodies in a neutropenic rat model of Pseudomonas sepsis.
Authors: S M Opal, A S Cross, J C Sadoff, H H Collins, N M Kelly, G H Victor, J E Palardy, M W Bodmer
Journal: Journal of Clinical Investigation (1991)

Monoclonal antibodies (MAb) directed against bacterial lipopolysaccharide (LPS) and tumor necrosis factor-alpha (TNF) provide partial protection in experimental models of septic shock. To determine if additional benefit accrues from a combination of anti-TNF and anti-LPS MAb in the treatment of septic shock, a neutropenic rat model was developed to study active infection with Pseudomonas aeruginosa 12.4.4. Animals were treated intravenously with an irrelevant MAb (group 1); anti-TNF MAb (group 2); MAb directed against P. aeruginosa 12.4.4 LPS (group 3); or a combination of anti-TNF and anti-LPS MAb (group 4). None of the control animals in group 1 survived the 7-d period of neutropenia (0/16). In contrast, the survival rate was 44% in group 2 (P less than 0.02); 37% in group 3 (P less than 0.05); and 75% in group 4 (P less than 0.0002). The combination of monoclonal antibodies provided greater protection than either MAb given alone (P less than 0.05). Serum TNF levels during infection were significantly greater in groups 1 and 3 (20.1 +/- 3.3 U, mean +/- SE) than in groups 2 and 4 (0.9 +/- 0.8 U, P less than 0.0001). These results indicate that a combination of monoclonal antibodies to LPS and TNF have additive benefit in experimental Pseudomonas aeruginosa sepsis. This immunotherapeutic approach may be of potential utility in the management of serious, gram-negative bacterial infection in neutropenic patients.
Ventilation-induced Neutrophil Infiltration Depends on c-Jun N-Terminal Kinase
Authors: Li-Fu Li, Lunyin Yu, Deborah A. Quinn
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

Positive pressure ventilation with large VTs has been shown to cause release of cytokines, including macrophage inflammatory protein-2 (MIP-2), a functional equivalent of human interleukin-8. The mechanisms regulating ventilation-induced cytokine production are unclear. Based on our previous in vitro model of lung cell stretch, we hypothesized that high VT ventilation–induced MIP-2 production is dependent on the activation of the c-Jun N-terminal kinase (JNK). We exposed C57BL/6 mice to high VT (30 ml/kg) or low VT (6 ml/kg) mechanical ventilation for 5 hours. High VT ventilation–induced neutrophil migration into the lung, MIP-2 protein production, MIP-2 messenger RNA expression, and JNK activation. Large VT ventilation of JNK knockout mice and pharmacologic JNK inhibition with SP600125 attenuated neutrophil sequestration and blocked MIP-2 messenger RNA expression and MIP-2 production. We conclude that lung cell stretch in vivo results in increased lung neutrophil sequestration and increased MIP-2 production, which was, at least in part, dependent upon the JNK pathway.
Pharmacological Modulation of Pressure-Overload Cardiac Hypertrophy
Authors: Kit Wong, Kenneth R. Boheler, Mario Petrou, Magdi H. Yacoub
Journal: Circulation (1997)

Background Appropriate cardiac hypertrophy (CH) is necessary in several clinical settings, such as pulmonary artery banding in the two-stage arterial switch operation for transposition of the great arteries. Pressure-overload CH, however, produces ventricular dysfunction due to structural and molecular changes. The β 2 -adrenergic receptor agonist clenbuterol has been shown to induce CH without such adverse effects to the rat heart. This study was performed to determine its effects on left ventricular (LV) function, structure, and gene expression in pressure-overload CH. Methods and Results Sprague-Dawley rats were assigned to one of four groups: 1, sham-operated (n=15); 2, banding of ascending aorta (n=22); 3, banding+clenbuterol (n=18); and 4, banding+thyroxine (n=17). At the end of 3 weeks, groups 2, 3, and 4 showed an increase in LV mass index of 49.7±5.1%, 66.1±3.8%, and 47.6±4.6%, respectively, relative to group 1. A subgroup with severe CH (&gt;50%) in group 2 was found to have significantly impaired developed pressure and diastolic relaxation and an increase in passive stiffness, with significantly reduced LV expression of sarcoplasmic reticulum Ca 2+ -ATPase2a (SERCA2a) mRNA and increased LV collagen concentration. In comparison, similarly hypertrophied animals in groups 3 and 4 demonstrated improved developed pressure, normal relaxation and diastolic stiffness with normal collagen concentration, and a greater abundance of SERCA2a mRNA. Conclusions Clenbuterol administration in conjunction with pressure overload produces a specific type of CH with preserved LV function. In addition, an increase in LV mass was associated with less fibrosis and greater expression of SERCA2a mRNA than banding alone.
Prognostic Role of Incidental Pleural Effusion Diagnosed During Echocardiographic Evaluation
Authors: Süleyman Ercan, Vedat Davutoğlu, Gökhan Altunbaş, Muhammed Oylumlu, İbrahim Halil İnanç, Mehmet Kaplan, Murat Yüce, Orhan Özer
Journal: Journal of the American College of Cardiology (2013)
A model study of volume conductor effects on endocardial and intracavitary potentials.
Authors: D S Khoury, Y Rudy
Journal: Circulation Research (1992)

An idealized mathematical model was developed to study the effects of variations in conductive and geometric parameters on measured endocardial and intracavitary potentials. The model consists of a spherical multielectrode probe located eccentrically within a system of concentric spheres that represent a blood cavity, myocardium, lung region, and surface muscle layer. Solutions were found for endocardial and intracavitary probe potentials produced by two different configurations of equivalent myocardial sources: 1) multiple activation wave fronts oriented radially, representing global fronts in the myocardium; and 2) pairs of equal and opposite dipoles on a line oriented tangentially to the endocardial surface, representing cardiac sources during early ectopic activation. It was found that the complexities of the cardiac source configurations are reflected in the endocardial potential but not in the associated probe potential, which exhibits a smoothed-out, low-amplitude distribution. In addition, probe potential depends on probe size and location within the cavity. Furthermore, endocardial and probe potentials are influenced by variations in the conductivity of different regions; an increase in blood conductivity results in a decrease in both endocardial and probe potential magnitudes produced by either type of cardiac sources, and an increase in myocardial conductivity results in an increase in both potential magnitudes, whereas an increase in lung conductivity results in an increase in the magnitude of the potential produced by radial sources but a small decrease in the magnitude of the potential produced by tangential sources. The effects of variations in skeletal muscle conductivity are negligible. The volume conductor effects of myocardial anisotropy (9:1 anisotropy ratio) are to attenuate both endocardial and probe potentials by as much as 60% and 71%, respectively, for radial sources and by 96% and 85%, respectively, for tangential sources. In conclusion, volume conductor influences should be considered in the interpretation of measured cavity potentials. Multiple myocardial events are resolved in endocardial potentials but not in potentials measured by an intracavitary multielectrode probe. This observation indicates that for the purpose of resolving cardiac activity, efforts should be directed at inverse reconstruction of endocardial potentials from potentials measured with an intracavitary probe.
Cutaneous Responses to Allergen after Local Pretreatment with Beta‐Adrenoceptor Stimulating and Blocking Agents
Authors: Reidar Grönneberg, Kjell Strandberg, ÖSten Hägermark
Journal: Allergy (1980)

β‐Adrenoceptor stimulating agents possess anti‐allergic effects in vitro and in vivo. To study the mechanism of action further we compared in 10 atopic subjects the effects on allergen‐induced cutaneous reactions of intradermally (i.d.) injected prenalterol (1–10 μg) terbutaline (2.5‐250 ng) and KWD 2131 (100ng‐2.5 μg), i.e. compounds with preferential actions on β 1 ‐, β 2 , ‐adrenoceptors and on β‐adrenoceptors not fitting this classification. All injections were given according to a double‐blind design. Terbutaline and KWD 2131 produced a dose‐dependent inhibition of the skin reactions induced by injecting horse dander allergen 5 min later. Terbutaline was about 20 times as potent as KWD 2131 whereas prenalterol was inactive. Propranolol fully blocked the anti‐allergic effect produced by terbutaline. The results suggest that the cutaneous anti‐allergic effect of β‐adrenoceptor‐stimulating drugs is mediated via activation of β 2 ‐adrenoceptors, possibly on the mast cell, resulting in inhibition of mediator release.
Assisted dying legislation must wait until after UK election
Authors: Kathryn Godfrey
Journal: BMJ (2005)

Legislation to allow assisted suicide and voluntary euthanasia in the United Kingdom has moved one step closer to being implemented, with the publication of a House of Lords select committee report last week. The report on Joel Joffe's Assisted Dying for the Terminally Ill Bill called for the issue to be debated early in the next session of parliament. This bill will not go any further as parliament is being dissolved for the UK general election, to be held on 5 May.

Although the committee was divided on whether the law should be changed, it recommended that a future bill on the issue should be considered by a committee of the whole house. The new bill is likely to apply only in England and Wales, as Lord Joffe recommended. This is a step forward from the last …
Abstract A54: TACE-regulated TGF-alpha shedding drives GRB7-dependent invasion in triple-negative breast cancer cell lines
Authors: Veronica Calvo, Orsi Giricz, Paraic A. Kenny
Journal: Cancer Research (2013)

Abstract The Epidermal Growth Factor Receptor (EGFR) is frequently expressed in triple-negative breast cancer and is a marker of poor prognosis. We have also recently identified an EGFR-associated adaptor protein, GRB7, as being associated with reduced relapse-free survival in triple-negative breast cancer. In this study we have sought to define the mechanisms underlying the contributions of EGFR and GRB7 to triple-negative breast cancer progression. Because activating mutations in EGFR are very rare events in breast cancer, we screened breast tumor gene expression profiles to examine the distribution of EGFR ligand expression. Of the six known EGFR ligands, TGFalpha was expressed more highly in triple-negative breast tumors than in tumors of other subtypes. TGFalpha is synthesized as a transmembrane precursor requiring TACE/ADAM17-dependent proteolytic release in order to activate its receptor. In this study we show that an inhibitor of this proteolytic release blocks invasion, migration and colony formation by several triple-negative breast cancer cell lines. Each of these effects of the drug was reversed upon expression of a soluble TGFalpha mutant which does not require TACE activity to function, implicating this one metalloproteinase substrate as playing a critical role in these metastasis-related phenotypes. A cyclic peptide inhibitor of GRB7, G718-NATE, also blocked tumor cell invasion and colony formation in 3D culture. Importantly, cell lines overexpressing the soluble TGFalpha mutant remained sensitive to the effects of the GRB7 inhibitor, suggesting that a linear TACE-TGFalpha-EGFR-GRB7 signaling module is involved. We additionally demonstrate that GRB7 overexpression upregulates several pathways with roles in tumor cell proliferation, migration and survival. Taken together, these data demonstrate that TGFalpha is the key ligand for EGFR in triple-negative breast cancer and that it drives invasion and proliferation via GRB7. This work suggests that triple-negative breast tumors in which this pathway is active might benefit clinically from either EGFR or TACE inhibitors. Citation Format: Veronica Calvo, Orsi Giricz, Paraic A. Kenny. TACE-regulated TGF-alpha shedding drives GRB7-dependent invasion in triple-negative breast cancer cell lines. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Invasion and Metastasis; Jan 20-23, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;73(3 Suppl):Abstract nr A54.
Noninvasive Magnetic Resonance Imaging Evaluation of Endothelial Permeability in Murine Atherosclerosis Using an Albumin-Binding Contrast Agent
Authors: Alkystis Phinikaridou, Marcelo E. Andia, Andrea Protti, Andreas Indermuehle, Ajay Shah, Alberto Smith, Alice Warley, René M. Botnar
Journal: Circulation (2012)

Endothelial dysfunction promotes atherosclerosis and precedes acute cardiovascular events. We investigated whether in vivo magnetic resonance imaging with the use of an albumin-binding contrast agent, gadofosveset, could detect endothelial damage associated with atherosclerosis in apolipoprotein E-deficient (ApoE(-/-)) mice. Furthermore, we tested whether magnetic resonance imaging could noninvasively assess endothelial function by measuring the endothelial-dependent vasodilation in response to acetylcholine.ApoE(-/-) mice were imaged at 4, 8, and 12 weeks after commencement of a high-fat diet. Statin-treated ApoE(-/-) mice were scanned after 12 weeks of a high-fat diet. Wild-type mice were imaged before and 48 hours after injection of Russell's viper venom, an endothelial toxin. Delayed enhancement magnetic resonance imaging and T1 mapping of the brachiocephalic artery, 30 minutes after injection of gadofosveset, showed increased vessel wall enhancement and relaxation rate (R(1)) with progression of atherosclerosis in ApoE(-/-)(R(1) [s(-1)]: R(4 weeks) 2.42±0.35, R(8 weeks) 3.45±0.54, R(12 weeks) 3.83±0.52) and Russell's viper venom-injected wild-type mice (R(1)=4.57±0.86). Conversely, wild-type (R(1)=2.15±0.34) and statin-treated ApoE(-/-) (R(1)=3.0±0.65) mice showed less enhancement. Uptake of gadofosveset correlated with Evans blue staining, morphological changes of endothelial cells, and widening of the cell-cell junctions, suggesting that uptake occurs in regions of increased vascular permeability. Endothelial-dependent vasomotor responses showed vasoconstriction of the arteries of the ApoE(-/-) (-22.22±7.95%) and Russell's viper venom-injected (-10.37±17.60%) mice compared with wild-type mice (32.45±12.35%). Statin treatment improved endothelium morphology and function (-8.12±8.22%).We demonstrate the noninvasive assessment of endothelial permeability and function with the use of an albumin-binding magnetic resonance contrast agent. Blood albumin leakage could be a surrogate marker for the in vivo evaluation of interventions that aim to restore the endothelium.
Effects of combined administration of low dose atorvastatin and vitamin E on inflammatory markers and endothelial function in patients with heart failure
Authors: Dimitris Tousoulis, Charalambos Antoniades, Carmen Vassiliadou, Marina Toutouza, Christos Pitsavos, Costas Tentolouris, Athanasios Trikas, Christodoulos Stefanadis
Journal: European Journal of Heart Failure (2005)
Contrasting views on human population growth
Authors: A J McMichael, J Guillebaud, M. King
Journal: BMJ (1999)

World population reaches 6 billion on 12 October, according to the best guess of demographers. It has tripled in a single lifetime, is projected to increase by half as much again next century, and, if current declines in fertility falter, could yet double. We have heard such statistics before, to the point of population crisis fatigue Yet we are living through a spectacular phenomenon in demographic history. Three quarters of the 1000-fold increase in human numbers since agriculture emerged 10 000 years ago has occurred during this past century—75% of the absolute increase in 1% of the time.

The size of the human population is an important determinant of its condition. It is increasingly the combination of human numbers with levels of consumption and types of technology that determines the impact on the environment—and whether that impact exceeds the local or global carrying capacity. Humanity's response to this population surge is one crucial test of its wisdom. Put simply, there are two “wisdoms.”

The first wisdom denies that population increase is a cause for alarm. This view is common on the neoliberal right: complacent, consumerist, and laissez faire. Although population has been increasing a …
Massive Childhood Lead Poisoning: The Price of Nigerian Gold
Authors: Adrian Burton
Journal: Environmental Health Perspectives (2012)

Estimating the Population-Level Impact of Environmental Chemicals on IQ ScoresMany studies report the impact of various environmental chemicals on children's neurological development as "clinically insignificant."But this designation, which describes the individual child, does not always reflect the broader implications of exposure for the overall population-i.e., that a mild but frequent impact could add up to a substantial population-level burden.A new analysis establishes priorities for reducing adverse neurodevelopmental impacts for U.S. children aged 5 years and younger [EHP 120(4):501-507; Bellinger].The author assessed the population impact of various risk factors, including exposure to environmental chemicals, on Full-Scale IQ (FSIQ) scores.FSIQ values are a useful measure for such an assessment because past studies have shown that these scores correspond to work productivity and associated lifetime earnings.FSIQ declines therefore can be used to estimate economic consequences for various risk factors.The data necessary for such an analysis, including information on both prevalence of exposure and effects, were available for only 3 environmental chemicals: lead, methylmercury, and organophosphate pesticides.The loss in FSIQ points was also calculated for a variety of medical conditions, neurodevelopmental disorders, traumatic brain injury, failure to thrive as a result of neglect and abuse, and iron defici ency.Loss of IQ points attributable to each risk factor
A prospective study on the safety of sublingual immunotherapy in pregnancy
Authors: W. A. Shaikh, S. W. Shaikh
Journal: Allergy (2012)

The aim of this study was to determine the safety of sublingual immunotherapy in pregnancy, which has not yet been reported.One hundred and fifty-five patients received sublingual immunotherapy with either house dust mite (D. farinae) or a mixture of up to five allergens during 185 pregnancies. Twenty-four patients received sublingual immunotherapy for the first time during pregnancy. Follow-up data were analysed with regard to abortion, perinatal mortality, prematurity, toxaemia and congenital malformation. Two control groups did not receive immunotherapy; group A (85 patients) received budesonide 400 μg twice daily and group B (40 patients) received rescue salbutamol inhalation. All three groups were on appropriate avoidance measures.Six-year follow-up data for the sublingual immunotherapy group revealed an incidence of complications less than that in the general population and a higher incidence of complications in both control groups.This study concludes that sublingual immunotherapy is safe during pregnancy and is also safe when initiated for the first time in a pregnant patient.