tbuckley/cabot-search huggingface dataset:
The Quality of Ambulatory Care Delivered to Children in the United States
Authors: Rita Mangione-Smith, Alison H. DeCristofaro, Claude M. Setodji, Joan Keesey, David J. Klein, John L. Adams, Mark A. Schuster, Elizabeth A. McGlynn
Journal: New England Journal of Medicine (2007)

Little is known about the magnitude of deficits in the quality of care delivered to children, since comprehensive studies have been lacking.We assessed the extent to which care processes recommended for pediatric outpatients are delivered. Quality indicators were developed with the use of the RAND-UCLA modified Delphi method. Parents of 1536 children who were randomly selected from 12 metropolitan areas provided written informed consent to obtain medical records from all providers who had seen the children during the 2-year period before the date of study recruitment. Trained nurses abstracted these medical records. Composite quality scores were calculated by dividing the number of times indicated care was documented as having been ordered or delivered by the number of times a care process was indicated.On average, according to data in the medical records, children in the study received 46.5% (95% confidence interval [CI], 44.5 to 48.4) of the indicated care. They received 67.6% (95% CI, 63.9 to 71.3) of the indicated care for acute medical problems, 53.4% (95% CI, 50.0 to 56.8) of the indicated care for chronic medical conditions, and 40.7% (95% CI, 38.1 to 43.4) of the indicated preventive care. Quality varied according to the clinical area, with the rate of adherence to indicated care ranging from 92.0% (95% CI, 89.9 to 94.1) for upper respiratory tract infections to 34.5% (95% CI, 31.0 to 37.9) for preventive services for adolescents.Deficits in the quality of care provided to children appear to be similar in magnitude to those previously reported for adults. Strategies to reduce these apparent deficits are needed.
"Perfect Sight without Glasses"
Authors: A. S. Philps
Journal: BMJ (1941)

This attractive slogan, or some modification of it, makes its appearance every few years, and lately it has bobbed up again, this time in the programme of the B.B.C. Brains Trust.The public are recommended to read two books on the subject in which it is stated that perfect sight can be achieved by exercises (and one of the two insists on a diet as well) and without the aid of glasses.It can be said at once that neither of these books is to be taken seriously, and there is very little truth or sense in either.The purpose of this article is not to expose the tricks of ophthalmic quacks, but to state what can and what cannot be done by eye exercises.What Exercises Cannot Do No exercise has been devised which can make a large eye smaller or a small eye larger, or which can change the shape or refractive index of the eye in any permanent way.In other words, and it cannot be stated too clearly, exercises are not a substitute for glasses in long sight, short sight, or astigmatism.
Collagenous gastritis and collagenous colitis: a report with sequential histological and ultrastructural findings
Authors: A B Pulimood, B S Ramakrishna, M M Mathan
Journal: Gut (1999)

The case is reported of a young adult man with collagenous gastritis, an extremely rare disorder with only three case reports in the English literature, who subsequently presented with collagenous colitis. Sequential gastric biopsies showed a notable increase in thickness of the subepithelial collagen band. Ultrastructural study of gastric and rectal mucosa showed the characteristic subepithelial band composed of haphazardly arranged collagen fibres, prominent degranulating eosinophils, and activated pericryptal fibroblasts.
Perceptions of childhood immunization in a minority community: qualitative study
Authors: Lesley Henderson, Christopher Millett, Nicki Thorogood
Journal: Journal of the Royal Society of Medicine (2008)

Summary Objective To assess reasons for low uptake of immunization amongst orthodox Jewish families. Design Qualitative interviews with 25 orthodox Jewish mothers and 10 local health care workers. Setting The orthodox Jewish community in North East London. Main outcome measures Identification of views on immunization in the orthodox Jewish community. Results In a community assumed to be relatively insulated from direct media influence, word of mouth is nevertheless a potent source of rumours about vaccination dangers. The origins of these may lie in media scares that contribute to anxieties about MMR. At the same time, close community cohesion leads to a sense of relative safety in relation to tuberculosis, with consequent low rates of BCG uptake. Thus low uptake of different immunizations arises from enhanced feelings of both safety and danger. Low uptake was not found to be due to the practical difficulties associated with large families, or to perceived insensitive cultural practices of health care providers. Conclusions The views and practices of members of this community are not homogeneous and may change over time. It is important that assumptions concerning the role of religious beliefs do not act as an obstacle for providing clear messages concerning immunization, and community norms may be challenged by explicitly using its social networks to communicate more positive messages about immunization. The study provides a useful example of how social networks may reinforce or challenge misinformation about health and risk and the complex nature of decision making about children's health.
Incremental Value of Ultrasonic Tissue Characterization (Backscatter) in the Evaluation of Left Ventricular Myocardial Structure and Mechanics in Essential Arterial Hypertension
Authors: Vitantonio Di Bello, Davide Giorgi, Enrica Talini, Giulia Dell’ Omo, Caterina Palagi, Maria Francesca Romano, Roberto Pedrinelli, Mario Mariani
Journal: Circulation (2003)

Background— Ultrasonic backscatter parameters were analyzed in hypertensive patients and divided into groups according to both severity of left ventricular hypertrophy (LVH) (group A: no LVH [n=52]; B: mild to moderate LVH [n=55]; and C: severe LVH [n=10]) and left ventricular geometry (normal geometry [n=44]; concentric remodeling [n=8]; concentric hypertrophy [n=25]; and eccentric hypertrophy [n=40]). Methods and Results— We studied 117 male, essential hypertensive patients and 19 normotensive, age-matched (40±5 years), healthy subjects who served as controls. Ambulatory and office blood pressure measurements were taken and 2-dimensional Doppler echocardiography and ultrasonic myocardial integrated backscatter (IBS) were performed. A group from the hypertensive study population (n=16) was observed after a period of pharmacological antihypertensive treatment to determine the behavior of backscatter parameters in relation to eventual regression of left ventricular mass (LVM). The cyclic variation index (CVIs) of the backscatter signal at the septum level was grouped according to each LVM level and was 29.4±9.3 (controls), 15±11 (group A), 9.5±10 (group B), and −1.5±8.6 (group C) ( P &lt;0.001). CVI septum values grouped according to left ventricular geometry were 15±11 (normal geometry), 12±7 (concentric remodeling), 7±11 (concentric hypertrophy), and 7.8±11 (eccentric hypertrophy) ( P &lt;0.01). Follow-up data demonstrate a significant reduction of LVM after therapy, as well as a significant increase in CVIs toward normal values. Conclusions— Hypertensive patients with higher LVM had the worst prognosis; in fact, those patients had the most significant CVI alterations. Regression of LVM subsequent to chronic pharmacological therapy induces a normalization of ultrasonic backscatter parameters. Ultrasonic tissue characterization (backscatter) analysis could allow early identification of patients at risk of developing complications of hypertensive cardiopathy.
Evidence-based approach to exercise prescription in chronic heart failure
Authors: Steve E Selig, David L Hare
Journal: British Journal of Sports Medicine (2007)

The benefits of moderate exercise appear to outweigh the risks

The hallmark symptoms of chronic heart failure (CHF) are fatigue and breathlessness, leading to impaired quality of life and capacity for activities of daily living (ADLs). Exercise training has the potential to delay the onset of fatigue and breathlessness, not just in patients with CHF, but in all people who exercise regularly. However, cardiologists have been concerned with recommending exercise to their patients with CHF, owing to perceptions that habitual exercise training may accelerate the disease process via cardiac hypertrophy and remodelling, deterioration in central haemodynamics and neurohormonal overactivity. All of these have strong associations with increased morbidity and mortality in these patients. A further concern has been that of sudden death from exercise-induced arrhythmias and, to a lesser extent, severe perturbations in blood pressure. Exercise training in patients with CHF is a relatively recent development, and studies to date have generally been limited to clinically stable, younger (<65 years) and less complicated cases.1 Very few women have been studied. The mortality outcome data so far are limited to less than 20 studies of a total of approximately 1000 individuals. The purpose …
Chronic natural killer lymphoproliferative disorders: characteristics of an international cohort of 70 patients
Authors: E. Poullot, R. Zambello, F. Leblanc, B. Bareau, E. De March, M. Roussel, M.L. Boulland, R. Houot, A. Renault, T. Fest, G. Semenzato, T. Loughran, T. Lamy
Journal: Annals of Oncology (2014)
Merlin Deficiency Predicts FAK Inhibitor Sensitivity: A Synthetic Lethal Relationship
Authors: Irina M. Shapiro, Vihren N. Kolev, Christian M. Vidal, Yuwaraj Kadariya, Jennifer E. Ring, Quentin Wright, David T. Weaver, Craig Menges, Mahesh Padval, Andrea I. McClatchey, Qunli Xu, Joseph R. Testa, Jonathan A. Pachter
Journal: Science Translational Medicine (2014)

The goal of targeted therapy is to match a selective drug with a genetic lesion that predicts for drug sensitivity. In a diverse panel of cancer cell lines, we found that the cells most sensitive to focal adhesion kinase (FAK) inhibition lack expression of the neurofibromatosis type 2 (NF2) tumor suppressor gene product, Merlin. Merlin expression is often lost in malignant pleural mesothelioma (MPM), an asbestos-induced aggressive cancer with limited treatment options. Our data demonstrate that low Merlin expression predicts for increased sensitivity of MPM cells to a FAK inhibitor, VS-4718, in vitro and in tumor xenograft models. Disruption of MPM cell-cell or cell-extracellular matrix (ECM) contacts with blocking antibodies suggests that weak cell-cell adhesions in Merlin-negative MPM cells underlie their greater dependence on cell-ECM-induced FAK signaling. This provides one explanation of why Merlin-negative cells are vulnerable to FAK inhibitor treatment. Furthermore, we validated aldehyde dehydrogenase as a marker of cancer stem cells (CSCs) in MPM, a cell population thought to mediate tumor relapse after chemotherapy. Whereas pemetrexed and cisplatin, standard-of-care agents for MPM, enrich for CSCs, FAK inhibitor treatment preferentially eliminates these cells. These preclinical results provide the rationale for a clinical trial in MPM patients using a FAK inhibitor as a single agent after first-line chemotherapy. With this design, the FAK inhibitor could potentially induce a more durable clinical response through reduction of CSCs along with a strong antitumor effect. Furthermore, our data suggest that patients with Merlin-negative tumors may especially benefit from FAK inhibitor treatment.
Advanced glycosylation endproducts on erythrocyte cell surface induce receptor-mediated phagocytosis by macrophages. A model for turnover of aging cells.
Authors: H Vlassara, J Valinsky, M Brownlee, C Cerami, S Nishimoto, A Cerami
Journal: The Journal of Experimental Medicine (1987)

Glucose can react nonenzymatically with amino groups of proteins to form covalent Amadori products. With time these adducts undergo further rearrangements to form irreversible advanced glycosylation endproducts (AGE), which accumulate with protein age. A specific AGE, 2-(2-furoyl)-4(5)-(2-furanyl)-1H-imidazole (FFI), has been identified on proteins in vivo. We have recently shown that a macrophage receptor specifically recognizes and internalizes proteins modified by AGE such as FFI, thus preferentially degrading senescent macromolecules. Reasoning that cellular turnover may be mediated by macrophage recognition of AGE-membrane proteins, we prepared human RBCs with FFI attached chemically. Human monocytes were incubated with either FFI-RBCs, IgG-opsonized RBCs, or PBS-treated RBCs. Erythrophagocytosis of FFI-RBCs was significantly higher than that of PBS-RBCs (55 vs. 4%; p less than 0.0025) and almost as high as that of IgG-RBCs (70%), and was competitively inhibited by AGE-BSA. AGE-RBCs were also prepared by incubating RBCs with various sugars. Human monocytes showed a 15% ingestion of glucose-RBCs, and a 26% ingestion of glucose-6-phosphate-RBCs, compared to 6% for PBS-RBCs. Similarly, diabetic mouse RBCs were phagocytosed by nearly three times more cells (21%) than normal mouse RBCs when exposed to syngeneic mouse macrophages. This phagocytosis was competitively inhibited (70%) by addition of excess AGE-BSA. The in vivo half-life of 51Cr-labeled mouse FFI-RBCs injected into syngeneic mice was reduced to 7 d, as compared to a half-life of 20 d for the controls. These data suggest that the macrophage receptor for the removal of glucose-modified proteins may also mediate the endocytosis of RBCs with AGE formed on their surface, and thus be responsible in part for the removal of some populations of aging cells.
Surgical treatment of pulmonary aspergilloma
Authors: Jelmer Oor, Jos Bekaert, Johannes Daniels, Pieter Postmus, Koen Hartemink, Marinus Paul, Wolter Oosterhuis
Journal: European Respiratory Journal (2011)

Pulmonary aspergilloma or mycetoma is a ball-shaped fungal infection, which is mostly encountered in pre-existing pulmonary cavities. Local inflammation, high vascularity and pre-existing lung damage can complicate surgical resection. We aimed to describe our patient population, the employed surgical techniques and the postoperative follow-up.  We performed a retrospective analysis of all patients who underwent surgical resection for an aspergilloma between January 2003 and September 2010. Using the patient charts, we examined the clinical data as well as the type of surgical technique that was used. SPSS 17.0 (SPSS INC, Chicago, IL) was used for data analysis.  Twenty-three patients underwent surgical resection for pulmonary aspergilloma. Seventeen (74%) were men, the mean age was 53 years and 43% of the patients presented with hemoptysis. Underlying diseases included hematological malignancies (n=8), (a history of) tuberculosis (n=3) and M. Bechterew (n=2). The most frequently employed surgical techniques consisted of wedge resection (n=8), lobectomy (n=7), pneumonectomy (n= 2) and segmentectomy (n=2). The duration of the hospitalization after the first surgical resection varied from 5 to 141 days (median 17, IQR, 9-33,25). The median time required for the first surgical resection was 3:34 hours (IQR, 2:34-5:07). Six patients (26%) underwent a rethoracotomy. Four patients died within 6 months after surgery.  Comorbidities were common, the duration of the surgical resections and hospital admissions was long and rethoracotomy was required in 26% of the cases. This illustrates the technical challenges for the surgeon and necessitates treatment in expert centers.
Ethics and Medical Practices
Authors: A. Herbert Schwartz
Journal: JAMA (1969)

<h3>To the Editor:—</h3> Special articles, such as "Theories of Ethics and Medical Practice" by Chauncey D. Leake (<b>208</b>:842, 1969), present the historical perspective and an overview of the significant problem of ethics in modern medicine. Specific issues, such as informed consent, have again been discussed in generalities and platitudes. These do not suggest the degree to which they must be followed so that we may be certain that we have obtained ethical goals. In talking of informed consent, Dr. Leake states: Fletcher says that a doctor owes patients the truth as fully and as honestly as owing skill and proper care. This responsibility goes further to the use of every aspect of tact and gentleness... every care to avoid hastiness, casualness, and unpleasantness... a duty of every physician is honest exposition to patients in terminology suited to their intelligence. In clinical research, tact, honesty and truthful dealings with patients
Micro RNA analysis reveals novel genes in human systemic lupus erythematosus: miR-21 affects PDCD4 expression and regulates aberrant T cell responses
Authors: E Stagakis, P Verginis, M Nakou, G Bertsias, E Krasoudaki, E Choustoulaki, H Kritikos, D Iliopoulos, D T Boumpas
Journal: Annals of the Rheumatic Diseases (2010)

MicroRNAs (miRNAs) are potent negative regulators of gene expression involved in innate and adaptive immune responses. The authors examined whether miRNAs are implicated in immune deregulation and lymphocyte hyperactivity in human systemic lupus erythematosus (SLE).

TaqMan miRNA arrays were used to study the expression of 365 miRNAs. …
Mitochondrial Dysfunction in Atherosclerosis
Authors: Nageswara R. Madamanchi, Marschall S. Runge
Journal: Circulation Research (2007)

Increased production of reactive oxygen species in mitochondria, accumulation of mitochondrial DNA damage, and progressive respiratory chain dysfunction are associated with atherosclerosis or cardiomyopathy in human investigations and animal models of oxidative stress. Moreover, major precursors of atherosclerosis—hypercholesterolemia, hyperglycemia, hypertriglyceridemia, and even the process of aging—all induce mitochondrial dysfunction. Chronic overproduction of mitochondrial reactive oxygen species leads to destruction of pancreatic β-cells, increased oxidation of low-density lipoprotein and dysfunction of endothelial cells—factors that promote atherosclerosis. An additional mechanism by which impaired mitochondrial integrity predisposes to clinical manifestations of vascular diseases relates to vascular cell growth. Mitochondrial function is required for normal vascular cell growth and function. Mitochondrial dysfunction can result in apoptosis, favoring plaque rupture. Subclinical episodes of plaque rupture accelerate the progression of hemodynamically significant atherosclerotic lesions. Flow-limiting plaque rupture can result in myocardial infarction, stroke, and ischemic/reperfusion damage. Much of what is known on reactive oxygen species generation and modulation comes from studies in cultured cells and animal models. In this review, we have focused on linking this large body of literature to the clinical syndromes that predispose humans to atherosclerosis and its complications.
Molecular cloning of the human Goodpasture antigen demonstrates it to be the alpha 3 chain of type IV collagen.
Authors: N Turner, P J Mason, R Brown, M Fox, S Povey, A Rees, C D Pusey
Journal: Journal of Clinical Investigation (1992)

To characterize the autoantigen of Goodpasture's (anti-glomerular basement membrane) disease, a molecule of 26-kD reactive with autoantibodies from patients' sera was purified from collagenase digests of sheep glomerular basement membrane. Short internal amino acid sequences were obtained after tryptic or cyanogen bromide cleavage, and used to deduce redundant oligonucleotides for use in the polymerase chain reaction on cDNA derived from sheep renal cortex. Molecules of 175 bp were amplified and found to come from two cDNA sequences. One was identical to that of a type IV collagen chain (alpha 5) cloned from human placenta and shown to be expressed in human kidney. The other was from a type IV collagen chain with close similarities to alpha 1 and alpha 5 chains, and was used to obtain human cDNA sequences by cDNA library screening and by further polymerase chain reaction amplifications. The correspondence of the derived amino acid sequence of the new chain with published protein and cDNA sequences shows it to be the alpha 3 chain of type IV collagen. Its gene, COL4A3, maps to 2q36-2q37. The primary sequence and other characteristics of this chain confirm that it carries the Goodpasture antigen.
Swim training sensitizes myocardial response to insulin: Role of Akt-dependent eNOS activation
Authors: Q ZHANG, Q LI, H ZHANG, K ZHANG, W GUO, H WANG, Z ZHOU, H CHENG, J REN, F GAO
Journal: Cardiovascular Research (2007)

Objectives Physical activity has been well known to benefit heart function. The improved autonomic nervous activity is considered to be mainly responsible for this beneficial effect. However, the precise mechanism behind the intrinsic myocardial responsiveness to exercise is still unclear. This study was designed to examine the effect of swim training on myocardial response to insulin with a special focus on the endogenous endothelial nitric oxide synthase (eNOS)–nitric oxide (NO) cascade.
Genetic factors underlying discordance in chromatin accessibility between monozygotic twins
Authors: Kwoneel Kim, Hyo-Jeong Ban, Jungmin Seo, Kibaick Lee, Maryam Yavartanoo, Sang Cheol Kim, Kiejung Park, Seong Beom Cho, Jung Kyoon Choi
Journal: Genome biology (2014)

Abstract Background Open chromatin is implicated in regulatory processes; thus, variations in chromatin structure may contribute to variations in gene expression and other phenotypes. In this work, we perform targeted deep sequencing for open chromatin, and array-based genotyping across the genomes of 72 monozygotic twins to identify genetic factors regulating co-twin discordance in chromatin accessibility. Results We show that somatic mutations cause chromatin discordance mainly via the disruption of transcription factor binding sites. Structural changes in DNA due to C:G to A:T transversions are under purifying selection due to a strong impact on chromatin accessibility. We show that CpGs whose methylation is specifically regulated during cellular differentiation appear to be protected from high mutation rates of 5′-methylcytosines, suggesting that the spectrum of CpG variations may be shaped fully at the developmental level but not through natural selection. Based on the association mapping of within-pair chromatin differences, we search for cases in which twin siblings with a particular genotype had chromatin discordance at the relevant locus. We identify 1,325 chromatin sites that are differentially accessible, depending on the genotype of a nearby locus, suggesting that epigenetic differences can control regulatory variations via interactions with genetic factors. Poised promoters present high levels of chromatin discordance in association with either somatic mutations or genetic-epigenetic interactions. Conclusion Our observations illustrate how somatic mutations and genetic polymorphisms may contribute to regulatory, and ultimately phenotypic, discordance.