tbuckley/cabot-search huggingface dataset:
Screening and Surveillance for Barrett Esophagus in High-Risk Groups: A CostUtility Analysis
Authors: John M. Inadomi, Richard Sampliner, Jesper Lagergren, David Lieberman, A Mark Fendrick, Nimish Vakil
Journal: Annals of Internal Medicine (2003)

Background: Once-in-a-lifetime screening for Barrett esophagus has been proposed for patients with gastroesophageal reflux disease (GERD), but there is little evidence of its cost-effectiveness. Objective: 1] To determine the cost-effectiveness of screening high-risk groups for Barrett esophagus and providing surveillance to patients with Barrett esophagus and dysplasia or to all patients with Barrett esophagus and 2) to compare the results with the cost-effectiveness of no screening or surveillance. Design: A decision analytic model was developed to examine no screening or surveillance and screening and surveillance for Barrett esophagus with dysplasia only or Barrett esophagus without dysplasia every 2 to 5 years. Low- or high-grade dysplasia received surveillance every 6 or 3 months, respectively. Data Sources: Published literature and the Health Care Financing Administration. Target Population: 50-year-old white men with symptoms of GERD. Time Horizon: 50 years of age until 80 years of age or death. Perspective: Third-party payer. Outcome Measure: Incremental cost-effectiveness ratio. Results of Base-Case Analysis: Screening with surveillance limited to patients with Barrett esophagus with dysplasia required $10 440 per quality-adjusted life-year (QALY) saved compared to no screening or surveillance. The incremental cost-effectiveness ratio of surveillance every 5 years in patients with Barrett esophagus without dysplasia compared to surveillance of patients with Barrett esophagus with dysplasia was $596 000 per QALY saved. Results of Sensitivity Analysis: The annual incidence of adenocarcinoma must exceed 1 case per 54 patient-years of follow-up (1.9%) for surveillance of Barrett esophagus without dysplasia every 5 years to yield an incremental cost-effectiveness ratio less than $50 000 per QALY saved. Conclusions: Screening 50-year-old men with symptoms of GERD to detect adenocarcinoma associated with Barrett esophagus is probably cost-effective. However, subsequent surveillance of patients with Barrett esophagus but no dysplasia, even at 5-year intervals, is an expensive practice.
The Economic Impact of a Primary Care Clinic
Authors: Paul W. Kolodzik
Journal: JAMA (1989)

To the Editor.—   article entitled The Economic Impact and Multiplier Effect of a Family Practice Clinic on an Academic Medical Center by Schneeweiss et al1is a comprehensive analysis of charges generated by a supporting primary care clinic at an academic medical center. However, the authors fail to address a critical issue relevant to this topic.  issue I refer to is theactualfinancial benefit derived as the result of the existence of the clinic.  authors conclude that the primary care clinic and its patients are a substantial source of revenue to the hospital and its specialty services.  data presented support a conclusion that the primary care clinic is a substantial source of generated billings, but as no reference is made to the percentage of collection of these charges, the contribution of the clinic to actual revenues remains undetermined.   only reference to the payer
Twice daily N-acetylcysteine 600 mg for exacerbations of chronic obstructive pulmonary disease (PANTHEON): a randomised, double-blind placebo-controlled trial
Authors: Jin-Ping Zheng, Fu-Qiang Wen, Chun-Xue Bai, Huan-Ying Wan, Jian Kang, Ping Chen, Wan-Zhen Yao, Li-Jun Ma, Xia Li, Luca Raiteri, Marco Sardina, Yi Gao, Bai-Song Wang, Nan-Shan Zhong
Journal: The Lancet Respiratory Medicine (2014)
Cell cycle control, checkpoint mechanisms, and genotoxic stress.
Authors: R E Shackelford, W K Kaufmann, R S Paules
Journal: Environmental Health Perspectives (1999)

The ability of cells to maintain genomic integrity is vital for cell survival and proliferation. Lack of fidelity in DNA replication and maintenance can result in deleterious mutations leading to cell death or, in multicellular organisms, cancer. The purpose of this review is to discuss the known signal transduction pathways that regulate cell cycle progression and the mechanisms cells employ to insure DNA stability in the face of genotoxic stress. In particular, we focus on mammalian cell cycle checkpoint functions, their role in maintaining DNA stability during the cell cycle following exposure to genotoxic agents, and the gene products that act in checkpoint function signal transduction cascades. Key transitions in the cell cycle are regulated by the activities of various protein kinase complexes composed of cyclin and cyclin-dependent kinase (Cdk) molecules. Surveillance control mechanisms that check to ensure proper completion of early events and cellular integrity before initiation of subsequent events in cell cycle progression are referred to as cell cycle checkpoints and can generate a transient delay that provides the cell more time to repair damage before progressing to the next phase of the cycle. A variety of cellular responses are elicited that function in checkpoint signaling to inhibit cyclin/Cdk activities. These responses include the p53-dependent and p53-independent induction of Cdk inhibitors and the p53-independent inhibitory phosphorylation of Cdk molecules themselves. Eliciting proper G1, S, and G2 checkpoint responses to double-strand DNA breaks requires the function of the Ataxia telangiectasia mutated gene product. Several human heritable cancer-prone syndromes known to alter DNA stability have been found to have defects in checkpoint surveillance pathways. Exposures to several common sources of genotoxic stress, including oxidative stress, ionizing radiation, UV radiation, and the genotoxic compound benzo[a]pyrene, elicit cell cycle checkpoint responses that show both similarities and differences in their molecular signaling.
Extent of centrilobular and panacinar emphysema in smokers' lungs: pathological and mechanical implications
Authors: M Saetta, WD Kim, JL Izquierdo, H Ghezzo, MG Cosio
Journal: European Respiratory Journal (1994)

In order to quantify the extent of centrilobular (CLE) and panacinar (PLE) emphysema and the degree of the possible overlap between the two forms in smokers, the lungs of 25 smokers undergoing lung resection for peripheral lung tumours were studied. The extent of CLE and PLE was assessed by point counting, and the lungs were classified as having pure CLE (C, n = 5), predominant CLE with areas of PLE (CP, n = 7), predominant PLE with features of CLE (PC, n = 7), and pure PLE (P, n = 6) according to the percentage of lung involved by either form. Preoperative pulmonary function tests and the score of inflammation and the diameters of the small airways were also measured. Mean linear intercept (Lm), a measure of mean interalveolar wall distances and forced expiratory volume in one second (FEV1) were similar in the four groups. Small airway pathology was a predominant feature in lungs with CLE, and was significantly decreased in a stepwise fashion as the amount of PLE increased. This was especially so for the amount of muscle in the airway wall and the diameters of the airways. By contrast, lung compliance was higher in panacinar than in centrilobular emphysema.(ABSTRACT TRUNCATED AT 250 WORDS)
Abstract 4504: Potential use of polyethyleneimine as a gene delivery vehicle for breast cancer.
Authors: T. J. Thomas, Sripriya Venkiteswaran, Thresia Thomas
Journal: Cancer Research (2013)

Abstract Breast cancer is the second leading cause of cancer death in US women, after lung cancer. A major impediment in advancing gene therapy approaches to breast cancer is the resistance of cancer cell membrane to transport DNA/RNA. Viral vectors are efficient to deliver target genes; however, they are associated with the risk of immune response, random integration into the host genome or recombination with other wild type viruses. In contrast, non-viral vectors, that include lipoplex and polyplex forming carriers, are more advantageous as they are less expensive, easier to manufacture, and can carry large molecules of DNA. Polyethyleneimine (PEI) has emerged as a very effective gene transfection agent. PEI is water soluble, positively charged, and can envelope negatively charged DNA and protect it from lysosomal degradation. However, gene transfection efficacy of PEI for breast cancer cells remains poorly understood. In addition, information on the relationship between the polymer structure and its biological function, such as DNA condensation, toxicity and transfection efficacy is still limited. In this study, we evaluated the transfection efficiency of PEIs differing in molecular weight and branching. pGL3 control plasmid (5256 bp) containing a coding for the firefly luciferase gene driven by the SV40 promoter was used for this study. pGL3 complexed with different PEIs was tested for gene transfection study in breast cancer cells, using luciferase activity measurements with a luminometer. Cytotoxicity was measured by trypan blue exclusion assay. Static and dynamic laser light scattering was used to determine the ability of PEIs to condense plasmid DNA to nanoparticles and determine the size of the nanoparticles. Our results showed maximum transfection efficiency with 22 kDa linear PEI at N/P (nitrogen/phosphorus) ratio of 4.8 to 6. Linear and branched 25 kDa PEIs were less efficient than 22 kDa PEI. Low molecular weight (0.6 and 1.2 kDa) PEIs had negligible effect in transporting plasmid DNA, whereas 10 kDa PEI showed some activity. Cytotoxic effects of the PEIs were suppressed by DNA complexation. Both branched and linear PEIs condensed plasmid DNA to nanoparticles (hydrodynamic radius: ∼155 nm). Taken together, these results demonstrate structure-function relationships of PEIs in condensing and transporting plasmid DNA. Our results might be useful in selecting and improving the properties of PEI as a gene delivery vehicle for breast cancer. Citation Format: T. J. Thomas, Sripriya Venkiteswaran, Thresia Thomas. Potential use of polyethyleneimine as a gene delivery vehicle for breast cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4504. doi:10.1158/1538-7445.AM2013-4504
Glucagon-like peptide-1 receptors in the brain: controlling food intake and body weight
Authors: Laurie L. Baggio, Daniel J. Drucker
Journal: Journal of Clinical Investigation (2014)

The peptide hormone glucagon-like peptide-1 (GLP-1) enhances glucose-induced insulin secretion and inhibits both gastric emptying and glucagon secretion. GLP-1 receptor (GLP-1R) agonists control glycemia via glucose-dependent mechanisms of action and promote weight loss in obese and diabetic individuals. Nevertheless, the mechanisms and cellular targets transducing the weight loss effects remain unclear. Two recent studies in the JCI provide insight into the neurons responsible for this effect. Sisley et al. reveal that GLP-1R agonist-induced weight loss requires GLP-1Rs in the CNS, while Secher et al. reveal that a small peptide GLP-1R agonist penetrates the brain and activates a subset of GLP-1R-expressing neurons in the arcuate nucleus to produce weight loss. Together, these two studies elucidate pathways that inform strategies coupling GLP-1R signaling to control of body weight in patients with diabetes or obesity.
Role for integrin-linked kinase in mediating tubular epithelial to mesenchymal transition and renal interstitial fibrogenesis
Authors: Yingjian Li, Junwei Yang, Chunsun Dai, Chuanyue Wu, Youhua Liu
Journal: Journal of Clinical Investigation (2003)

Under pathologic conditions, renal tubular epithelial cells can undergo epithelial to mesenchymal transition (EMT), a phenotypic conversion that is believed to play a critical role in renal interstitial fibrogenesis. However, the underlying mechanism that governs this process remains largely unknown. Here we demonstrate that integrin-linked kinase (ILK) plays an important role in mediating tubular EMT induced by TGF-β1. TGF-β1 induced ILK expression in renal tubular epithelial cells in a time- and dose-dependent manner, which was dependent on intracellular Smad signaling. Forced expression of ILK in human kidney proximal tubular epithelial cells suppressed E-cadherin expression and induced fibronectin expression and its extracellular assembly. ILK also induced MMP-2 expression and promoted cell migration and invasion in Matrigel. Conversely, ectopic expression of a dominant-negative, kinase-dead form of ILK largely abrogated TGF-β1–initiated tubular cell phenotypic conversion. In vivo, ILK was markedly induced in renal tubular epithelia in mouse models of chronic renal diseases, and such induction was spatially and temporally correlated with tubular EMT. Moreover, inhibition of ILK expression by HGF was associated with blockade of tubular EMT and attenuation of renal fibrosis. These findings suggest that ILK is a critical mediator for tubular EMT and likely plays a crucial role in the pathogenesis of chronic renal fibrosis.
Southall cleared of conducting trial without parents' consent
Authors: C. Dyer
Journal: BMJ (2008)

<h3>Objective</h3> To determine whether on-scene BP is associated with early neurological deterioration (END) in patients with spontaneous intracerebral haemorrhage (SICH). <h3>Methods</h3> This retrospective cohort study enrolled consecutive ambulance-transported adult SICH patients treated at our emergency department (ED) from January 2007 through December 2012. END was defined as a ≥2-point decrease in GCS within 24 h of ED arrival. The exact relationship between on-scene BP and END was assessed using multiple logistic regression analyses for adjusting age, gender, Charlson Index, aspirin use, smoking, elapsed time, consciousness level on ED arrival, haematoma size, intraventricular extension, midline shift and infratentorial ICH. We further calculated the −2 log-likelihood decrease for each regression model incorporated with the BP values measured at different times to compare model fitness. <h3>Results</h3> After adjusting for the covariates, on-scene systolic BP (by 10 mm Hg incremental: OR = 1.126, 95% CI 1.015 to 1.265), diastolic BP (by 10 mm Hg incremental: OR=1.146, 95% CI 1.019 to 1.303) and mean arterial pressure (MAP) (by 10 mm Hg incremental: OR=1.225, 95% CI 1.057 to 1.443) were significantly associated with END; adding on-scene MAP into the regression model yielded the highest model fitness increase. Adding on-scene BPs into the regression model yielded higher model fitness increase than adding ED and admission BPs. <h3>Conclusions</h3> Few on-scene BP indices were associated with neuroworsening within 24 h after ED arrival in non-comatose SICH patients. Compared with BP measured on ED arrival or admission, on-scene BP had a stronger correlation with END.
Abstract 1362: Degradation of Cardiac Troponins in Atrial Fibrillation is Calpain-dependent
Authors: Lei Ke, Anne-Jan Dijkhuis, Robert H Henning, Harm H Kampinga, Bianca J Brundel
Journal: Circulation (2007)

Background: The self-perpeptuation of atrial fibrillation (AF) is caused by myocyte remodeling including degradation of cardiac troponins. Additionally, we observed enhanced calpain activity in human AF and in the tachypaced cell model for AF. We assessed the hypothesis that calpain plays a role in the degradation of cardiac troponins during AF. Methods: The tachypaced HL-1 atrial myocyte model was used to investigate degradation of endogenous cardiac troponin T, I and C (cTnT, cTnI, cTnC) as well as actin by Western-blotting. To study degradation of human cTnT, myocytes were transfected with V5-C-human cTnT. Inhibitors of calpain, caspase and proteasome were applied to study the underlying mechanism for degradation. In vivo cTn degradation was studied in atrial tissue from AF and sinus rhythm (SR) patients by Western-blotting. Results: Tachypacing (P, 3Hz) significantly and gradually induced the degradation of cTnT (Fig A ), cTnI and cTnC, compared to control (C, 1Hz), while actin were unaffected. The degradation was prevented by calpain inhibitor PD150606 (20μM), whereas caspase (CAS) and proteasome (MG) inhibition was not effective (Fig C ). Tachypacing of V5-C-human cTnT transfected HL-1 myocytes resulted in a specific degradation fragment of 25kDa, which was prevented by PD (Fig B ). In vivo, persistent AF was associated with specific degradation of cTnT, I and C, compared to patients with SR or paroxysmal AF. Actin levels were not changed. Conclusions: AF induces specific degradation of all cTn isoforms, which is mediated by calpain. Activation of calpain may represent a key component in linking cTn degradation, contractile dysfunction and the self-perpetuation of AF.
Brief-Exposure Break-Bone Fever-Reply
Authors: Michael D. Malison
Journal: JAMA (1983)

<h3>In Reply.—</h3> Drs D'Angelo and Burris raise a point in their case report about group B arbovirus (flavivirus) serology that is well known to arbovirologists but was beyond the scope of our brief review of dengue. That is, while patients with primary flavivirus infections often have a specific antibody response, a heterologous antibody response occurs in secondary infections, which makes infecting virus type identification by hemagglutination inhibition, complement fixation, or virus neutralization virtually impossible.<sup>1</sup>An exception might be tests for neutralizing antibodies with serum from a person for whom the first flavivirus infecting type is well documented. The only reliable way of identifying virus serotype in patients with secondary infections, therefore, is by virus isolation. Virus isolation is accomplished by inoculating serum into mosquitoes or mosquito culture. These techniques, developed and improved during the past ten years, have made dengue virus isolation a relatively easy process. Identification of dengue
A MODIFIED EXTRACTOR FOR THE REMOVAL OF VARICOSE VEINS OF THE LEG
Authors: W. WAYNE BABCOCK
Journal: JAMA (1910)

This instrument is a modification of the simple device I described in 1907,<sup>1</sup>for the removal of varicose veins of the leg. The larger acorn tip of the instrument has been increased in size and its surface toward the shaft of the instrument so cupped as to catch the wall of the vein and prevent its inversion and slipping over the end of the instrument. In using the instru.nl the vein is exposed either at the upper or lower termination of the segment to be removed. With the internal saphenous vein, which is most frequently extirpated, the exposure is made either just below the saphenous opening in the thigh or on the inside of the calf of the leg. The vein is exposed, grasped with hemostatic forceps, incised and the smaller end of the instrument slipped into the lumen of the vein for the required distance or until some obstruction is
Antibody-Mediated Rejection in Cardiac Transplantation: Emerging Knowledge in Diagnosis and Management
Authors: Monica M. Colvin, Jennifer L. Cook, Patricia Chang, Gary Francis, Daphne T. Hsu, Michael S. Kiernan, Jon A. Kobashigawa, JoAnn Lindenfeld, Sofia Carolina Masri, Dylan Miller, John O’Connell, E. Rene Rodriguez, Bruce Rosengard, Sally Self, Connie White-Williams, Adriana Zeevi
Journal: Circulation (2015)
Bronchopulmonary lymph nodes and large airway cell trafficking in patients with fatal asthma
Authors: Erika Feltrini Cagnoni, Diogenes Seraphim Ferreira, Luiz Fernando Ferraz da Silva, Ana Laura Nicoletti Carvalho Petry, Angela Batista Gomes dos Santos, Maria Cristina Rodrigues Medeiros, Marisa Dolhnikoff, Klaus F. Rabe, Thais Mauad
Journal: Journal of Allergy and Clinical Immunology (2014)
Sex differences in the determinants of left ventricular mass in childhood. The Medical College of Virginia Twin Study.
Authors: M M Goble, M Mosteller, W B Moskowitz, R M Schieken
Journal: Circulation (1992)

BACKGROUND Left ventricular (LV) hypertrophy is a predictor of cardiovascular events in adults and has been observed in children and adolescents with hypertension. We wanted to establish the determinants of LV mass in normotensive preadolescent children. Our objectives were 1) to produce a simplified and generalizable model of the clinical variables that determine normal cardiac growth during childhood and 2) to understand better why males have an increased LV mass relative to females, even as children. METHODS AND RESULTS In a group of 243 eleven-year-old children, we analyzed anthropometric, hemodynamic, and echocardiographic data to define which variables were predictors of echocardiographically determined LV mass. Stepwise regression was used to predict LV mass overall, by sex, and by body size (body mass index). Overall, LV mass was directly related to weight, male sex, and systolic and diastolic blood pressure and inversely related to resting heart rate and skin-fold thicknesses. Systolic blood pressure was a determinant in boys but not in girls. Heart rate was a weak inverse correlate in both sexes. When the data were analyzed by body mass index quartile, weight was the sole predictor of LV mass in the largest children. CONCLUSIONS We conclude that in normotensive preadolescent children, 1) weight, but not pondersity, is a strong predictor of LV mass; 2) body fat is negatively associated with LV mass; 3) boys have an increased LV mass relative to girls; and 4) boys and girls have similar anthropometric determinants and may have different hemodynamic determinants. Our data suggest that body size, and in particular lean body mass, explains much of the variability in cardiac growth seen in children. The influence of hemodynamic variables seems to be more limited. Our findings are of general interest because, although hypertensive heart disease is well described, the early developmental stages are not well understood.
INTERTRIGO (CHAFING) TREATED WITH TANNIC ACID AND BRILLIANT GREEN
Authors: Louis Tulipan
Journal: JAMA (1941)

Literature on intertrigo, a distressingly common disease, is exceedingly scarce, particularly in the United States. Therefore, in order to make clear the logic of the proposed therapy, I shall briefly review its known causes and symptoms. Intertrigo results from friction of apposing surfaces of the skin and occurs in the following locations: the groins, the intergluteal folds, the inner sides of the thighs, the axillas, the submammary folds of women, the hypogastric fold, the retroauricular fold and the folds of the neck, groins and buttocks of newborn infants. Additional etiologic factors are obesity, excessive perspiration, heat, fungous or bacterial infection and regional secretions such as urine, feces, serous or purulent discharges, vaginal discharges and menstrual fluid. The condition may manifest itself on the skin as a mild erythema, a vesicular or papular eruption similar to that of lichen tropicus (prickly heat) or as a vesicular, papular, or lichenified eczema which