tbuckley/cabot-search huggingface dataset:
Infections With Oseltamivir-Resistant Influenza A(H1N1) Virus in the United States
Authors: Nila J. Dharan
Journal: JAMA (2009)

During the 2007-2008 influenza season, oseltamivir resistance among influenza A(H1N1) viruses increased significantly for the first time worldwide. Early surveillance data suggest that the prevalence of oseltamivir resistance among A(H1N1) viruses will most likely be higher during the 2008-2009 season.To describe patients infected with oseltamivir-resistant influenza A(H1N1) virus and to determine whether there were any differences between these patients and patients infected with oseltamivir-susceptible A(H1N1) virus in demographic or epidemiological characteristics, clinical symptoms, severity of illness, or clinical outcomes.Influenza A(H1N1) viruses that were identified and submitted to the Centers for Disease Control and Prevention by US public health laboratories between September 30, 2007, and May 17, 2008, and between September 28, 2008, and February 19, 2009, were tested as part of ongoing surveillance. Oseltamivir resistance was determined by neuraminidase inhibition assay and pyrosequencing analysis. Information was collected using a standardized case form from patients with oseltamivir-resistant A(H1N1) infections and a comparison group of patients with oseltamivir-susceptible A(H1N1) infections during 2007-2008.Demographic and epidemiological information as well as clinical information, including symptoms, severity of illness, and clinical outcomes.During the 2007-2008 season, influenza A(H1N1) accounted for an estimated 19% of circulating influenza viruses in the United States. Among 1155 influenza A(H1N1) viruses tested from 45 states, 142 (12.3%) from 24 states were resistant to oseltamivir. Data were available for 99 oseltamivir-resistant cases and 182 oseltamivir-susceptible cases from this period. Among resistant cases, median age was 19 years (range, 1 month to 62 years), 5 patients (5%) were hospitalized, and 4 patients (4%) died. None reported oseltamivir exposure before influenza diagnostic sample collection. No significant differences were found between cases of oseltamivir-resistant and oseltamivir-susceptible influenza in demographic characteristics, underlying medical illness, or clinical symptoms. Preliminary data from the 2008-2009 influenza season identified resistance to oseltamivir among 264 of 268 influenza A(H1N1) viruses (98.5%) tested.Oseltamivir-resistant A(H1N1) viruses circulated widely in the United States during the 2007-2008 influenza season, appeared to be unrelated to oseltamivir use, and appeared to cause illness similar to oseltamivir-susceptible A(H1N1) viruses. Circulation of oseltamivir-resistant A(H1N1) viruses will continue, with a higher prevalence of resistance, during the 2008-2009 season.
Atrium-Specific Kir3.x Determines Inducibility, Dynamics, and Termination of Fibrillation by Regulating Restitution-Driven Alternans
Authors: Brian O. Bingen, Zeinab Neshati, Saïd F.A. Askar, Ivan V. Kazbanov, Dirk L. Ypey, Alexander V. Panfilov, Martin J. Schalij, Antoine A.F. de Vries, Daniël A. Pijnappels
Journal: Circulation (2013)

Atrial fibrillation is the most common cardiac arrhythmia. Ventricular proarrhythmia hinders pharmacological atrial fibrillation treatment. Modulation of atrium-specific Kir3.x channels, which generate a constitutively active current (I(K,ACh-c)) after atrial remodeling, might circumvent this problem. However, it is unknown whether and how I(K,ACh-c) contributes to atrial fibrillation induction, dynamics, and termination. Therefore, we investigated the effects of I(K,ACh-c) blockade and Kir3.x downregulation on atrial fibrillation.Neonatal rat atrial cardiomyocyte cultures and intact atria were burst paced to induce reentry. To study the effects of Kir3.x on action potential characteristics and propagation patterns, cultures were treated with tertiapin or transduced with lentiviral vectors encoding Kcnj3- or Kcnj5-specific shRNAs. Kir3.1 and Kir3.4 were expressed in atrial but not in ventricular cardiomyocyte cultures. Tertiapin prolonged action potential duration (APD; 54.7±24.0 to 128.8±16.9 milliseconds; P<0.0001) in atrial cultures during reentry, indicating the presence of I(K,ACh-c). Furthermore, tertiapin decreased rotor frequency (14.4±7.4 to 6.6±2.0 Hz; P<0.05) and complexity (6.6±7.7 to 0.6±0.8 phase singularities; P<0.0001). Knockdown of Kcnj3 or Kcnj5 gave similar results. Blockade of I(K,ACh-c) prevented/terminated reentry by prolonging APD and changing APD and conduction velocity restitution slopes, thereby altering the probability of APD alternans and rotor destabilization. Whole-heart mapping experiments confirmed key findings (e.g., >50% reduction in atrial fibrillation inducibility after I(K,ACh-c) blockade).Atrium-specific Kir3.x controls the induction, dynamics, and termination of fibrillation by modulating APD and APD/conduction velocity restitution slopes in atrial tissue with I(K,ACh-c). This study provides new molecular and mechanistic insights into atrial tachyarrhythmias and identifies Kir3.x as a promising atrium-specific target for antiarrhythmic strategies.
Genetic contribution to radiographic severity in osteoarthritis of the knee
Authors: Ana M Valdes, Sally Doherty, Kenneth R Muir, Weiya Zhang, Rose A Maciewicz, Margaret Wheeler, Nigel Arden, Cyrus Cooper, M Doherty
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Objective</h3> Knee osteoarthritis (OA) has a significant genetic component. The authors have assessed the role of three variants reported to influence risk of knee OA with p&lt;5×10–8 in determining patellofemoral and tibiofemoral Kellgren Lawrence (K/L) grade in knee OA cases. <h3>Methods</h3> 3474 knee OA cases with sky-line and weight-bearing antero-posterior x-rays of the knee were selected based on the presentation of K/L grade ≥2 at either the tibiofemoral or patellofemoral compartments for one or both knees. Patients belonging to three UK cohorts, were genotyped for rs143383, rs4730250 and rs11842874 mapping to the <i>GDF5</i>, <i>COG5</i> and <i>MCF2L</i> genes, respectively. The association between tibiofemoral K/L grade and patellofemoral K/L grade was assessed after adjusting for age, gender and body mass index. <h3>Results</h3> No significant association was found between the rs4730250 and radiographic severity. The rs11842874 mapping to <i>MCF2L</i> was found to be nominally significantly associated with patellofemoral K/L grade as a quantitative trait (p=0.027) but not as a binary trait. The <i>GDF5</i> single nucleotide polymorphism rs143383 was associated with tibiofemoral K/L grade (β=0.05 (95% CI 0.02 to 0.08) p=0.0011). <h3>Conclusions</h3> Our data indicate that within individuals affected by radiographic knee OA, OAGDF5 has a modest but significant effect on radiographic severity after adjustment for the major risk factors.
Can rheumatologists agree on a diagnosis of inflammatory arthritis in an early synovitis clinic?
Authors: G GORMLEY
Journal: Annals of the Rheumatic Diseases (2001)

It is argued that an important aspect of rehabilitation after severe head injury lies in training or retraining victims in skills required for independent living. Despite this, very little is known about the training characteristics of head injured patients. It is shown that in the acquisition of a psychomotor skill severely head injured subjects have very poor starting levels as compared to normal controls. They show impressive learning to the extent that they considerably close the gap between themselves and the controls. They also show appreciable transfer of the learned skill from one version of the task to another. The findings are discussed in terms of their implications for further understanding of the training process in head injured subjects in ways that could reflect upon clinical practice in rehabilitation.
Effects of Respiration and Gravity on Infradiaphragmatic Venous Flow in Normal and Fontan Patients
Authors: T.-Y. Hsia, S. Khambadkone, A. N. Redington, F. Migliavacca, J. E. Deanfield, M. R. de Leval
Journal: Circulation (2000)

In the Fontan circulation, pulmonary and systemic vascular resistances are in series. The implications of this unique arrangement on infradiaphragmatic venous physiology are poorly understood.We studied the effects of respiration and gravity on infradiaphragmatic venous flows in 20 normal healthy volunteers (control) and 48 Fontan patients (atriopulmonary connection [APC] n=15, total cavopulmonary connection [TCPC] n=30). Hepatic venous (HV), subhepatic inferior vena caval (IVC), and portal venous (PV) flow rates were measured with Doppler ultrasonography during inspiration and expiration in both the supine and upright positions. The inspiratory-to-expiratory flow rate ratio was calculated to reflect the effect of respiration, and the supine-to-upright flow rate ratio was calculated to assess the effect of gravity. HV flow depended heavily on inspiration in TCPC compared with both control and APC subjects (inspiratory-to-expiratory flow rate ratio 3.4, 1.7, and 1.6, respectively; P:<0.0001). Normal PV flow was higher in expiration, but this effect was lost in TCPC and APC patients (inspiratory-to-expiratory flow rate ratio 0.8, 1.0, and 1.1, respectively; P:=0.01). The respiratory influence on IVC flow was the same in all groups. Gravity decreased HV flow more in APC than in TCPC patients (supine-to-upright flow rate ratio 3.2 versus 2.1, respectively; P:<0.04) but reduced PV flow equally in all groups.Gravity and respiration have important influences on infradiaphragmatic venous return in Fontan patients. Although gravity exerts a significant detrimental effect on lower body venous return, which is more marked in APC than in TCPC patients, the beneficial effects of respiration in TCPC patients are mediated primarily by an increase in HV flow. These effects may have important short- and long-term implications for the hemodynamics of the Fontan circulation.
Staphylococcal sepsis in HIV antibody seropositive psoriasis patients
Authors: David Jaffe, Lewis Pete May, Miguel Sanchez, Janet Moy
Journal: Journal of the American Academy of Dermatology (1991)

The cases of three HIV-positive men with generalized psoriasis and staphylococcal sepsis are reported. In each case the skin appeared to be the source of infection. While the patients received antibiotic therapy, the psoriatic plaques resolved despite minimal or no topical treatment. The cases of three HIV-positive men with generalized psoriasis and staphylococcal sepsis are reported. In each case the skin appeared to be the source of infection. While the patients received antibiotic therapy, the psoriatic plaques resolved despite minimal or no topical treatment.
The cutaneous infiltrates of leprosy. A transmission electron microscopy study.
Authors: G Kaplan, W C Van Voorhis, E N Sarno, N Nogueira, Z A Cohn
Journal: The Journal of Experimental Medicine (1983)

The dermal lesions of 18 patients with leprosy have been examined by transmission electron microscopy. The patients exhibited a spectrum of disease from polar lepromatous to polar tuberculoid with intermediate stages in various states of therapy and relapse. The nature and quantities of inflammatory cells and bacteria have been determined by electron microscopy to supplement previous light and fluorescence microscopy studies. Lepromatous leprosy was characterized by many parasitized foam cells containing large, multibacillary vacuoles with intact, osmiophilic Mycobacterium leprae: Bacteria were embedded in an electron-lucent matrix. No extracellular bacteria were evident. Only small numbers of scattered lymphocytes were found. As one approached the borderline state, smaller numbers of bacilli were present as singlets and doublets in small vacuoles of macrophages. The more reactive forms showed increasing bacillary fragmentation, larger numbers of lymphoid cells, and an occasional epithelioid cell. At the tuberculoid end of the spectrum, clear evidence of an exuberant lymphocyte response was evident. Large numbers of T cells with extremely long and complex filipodia were closely associated with epithelioid and multinucleated giant cells. Many of the mononuclear phagocytes appeared nonviable, and areas of necrosis were evident. Bacillary remnants were scarce and the cytoplasm of the epithelioid cells contained occasional dense bodies and many stacks of endoplasmic reticulum and mitochondria. These results suggest that Leu 3a/OKT4 helper cells may be capable of driving the effector function of mononuclear phagocytes. This would lead to a significant microbicidal effect on M. leprae, perhaps through the production of toxic oxygen intermediates.
Vermiculite, Respiratory Disease, and Asbestos Exposure in Libby, Montana: Update of a Cohort Mortality Study
Authors: Patricia A. Sullivan
Journal: Environmental Health Perspectives (2007)

Vermiculite from the mine near Libby, Montana, is contaminated with tremolite asbestos and other amphibole fibers (winchite and richterite). Asbestos-contaminated Libby vermiculite was used in loose-fill attic insulation that remains in millions of homes in the United States, Canada, and other countries.
Prevalence and clinical significance of auto-antibodies in adults with cystic fibrosis
Authors: F. Lachenal, K. Nkana, R. Nove-Josserand, N. Fabien, I. Durieu
Journal: European Respiratory Journal (2009)

The aim of this study was to determine the prevalence of different auto-antibodies in adult, French cystic fibrosis (CF) patients and to look for a correlation between autoimmunity, patient characteristics and survival. The sera of 144 patients were screened for a wide range of antibodies. Clinical, biological and bacteriological characteristics and the cystic fibrosis transmembrane conductance regulator genotype were recorded and progression of lung disease was examined. 113 (78.5%) patients displayed one or several auto-antibodies, predominantly immunoglobulin (Ig)A anti-<i>Saccharomyces cerevisiae</i> antibodies (ASCA; 43.7%) and antineutrophil cytoplasmic antibodies (ANCA; 40%), of which 59% showed bactericidal/permeability-increasing protein (BPI) specificity. The presence of BPI-ANCA was associated with the number of antibiotic courses, low body mass index, <i>Pseudomonas aeruginosa</i> colonisation, the presence of resistant <i>P. aeruginosa</i>, low forced expiratory volume in 1 s, CF-related liver disease, hypergammaglobulinaemia, male sex and inflammatory syndrome. The presence of ASCA-IgA was correlated with male sex and hypergammaglobulinaemia. 41 patients presented with chronic respiratory failure and/or requested lung transplantation or died during follow-up. These events were more frequent in patients with BPI-ANCA or ASCA-IgA. These findings confirm the high frequency of auto-antibodies in CF, particularly BPI-ANCA and ASCA-IgA, and the link between BPI-ANCA, severity of lung disease and CF prognosis.
Plasma cell mucositis of the distal airways
Authors: M R Lucarelli
Journal: Thorax (2005)

Plasma cell mucositis is a rare idiopathic condition consisting of a marked infiltration of mucosa by plasma cells that may involve the mucous membranes of the upper aerodigestive tract—namely, the oral mucosa, gingiva, supraglottic and glottic larynx, and the trachea. While plasma cell mucositis is usually considered benign, cases of critical stenosis of the upper airway have been reported.1,2 We present a case of plasma cell mucositis involving the trachea and bronchi. This pattern of lower respiratory tract involvement has not previously been described.

A 55 year old woman, a lifelong non-smoker, presented with chronic cough, dyspnoea, and stridor. Pulmonary function tests showed a moderately severe …
A Systems Approach to Model Metastatic Progression
Authors: Barry S. Taylor, Sooryanarayana Varambally, Arul M. Chinnaiyan
Journal: Cancer Research (2006)

Abstract Proteomic profiling of human disease has seen much early activity with the accessibility of the newest generation of high-throughput platforms and technologies. Nevertheless, the nature of the dynamic physiologic milieu and high dimensionality of the data has complicated major diagnostic and prognostic breakthroughs. Our recent article in Cancer Cell delineates an integrative model for culling a molecular signature of metastatic progression in prostate cancer from proteomic and transcriptomic analyses and shows its facility as a predictor of prognosis. The study leveraged direct proteomic analysis of tumor tissue extracts, differential feature selection characterizing the proteomic alterations of prostate cancer subclasses, and integration with public and study-derived genomic data to construct a multiplex gene signature representing progression of indolent cancer to aggressive disease. This further predicted clinical outcome in a variety of solid tumors. This review describes the context of the work, the framework for the analysis itself, and a look forward to the promise of this systems approach to human disease. (Cancer Res 2006; 66(11): 5537-9)
A Phase II Clinical Trial of Sorafenib in Androgen-Independent Prostate Cancer
Authors: William L. Dahut, Charity Scripture, Edwin Posadas, Lokesh Jain, James L. Gulley, Philip M. Arlen, John J. Wright, Yunkai Yu, Liang Cao, Seth M. Steinberg, Jeanny B. Aragon-Ching, Jürgen Venitz, Elizabeth Jones, Clara C. Chen, William D. Figg
Journal: Clinical Cancer Research (2008)

Abstract Purpose: To determine if sorafenib is associated with a 4-month probability of progression-free survival, which is consistent with 50%, as determined by clinical, radiographic, and prostate-specific antigen (PSA) criteria in patients with metastatic androgen-independent prostate cancer (AIPC). Experimental Design: Patients with progressive metastatic AIPC were enrolled in an open-label, single-arm phase II study. Sorafenib was given continuously at a dose of 400 mg orally twice daily in 28-day cycles. Clinical assessment and PSA measurement were done every cycle whereas radiographic measurements were carried out every two cycles. Results: Twenty-two patients were enrolled in the study to date, completing a planned first stage of the trial. Baseline patient characteristics included a median age of 63.9 years (range, 50-77 years), Gleason score of 9 (range, 4-9.5), and PSA concentration of 53.3 ng/mL (range, 2-1,905 ng/mL). Fifty-nine percent of patients had received one prior chemotherapy regimenn. Of the 21 patients with progressive disease, 13 progressed only by PSA criteria in the absence of evidence of clinical and radiographic progression. Two patients were found to have dramatic reduction of bone metastatic lesions as shown by bone scan, although they met PSA progression criteria at the time when scans were obtained. Toxicities likely related to treatment included one grade 3 hypertension; one grade 3 hand-foot syndrome; and grade 1/2 toxicities: fatigue, anorexia, hypertension, skin rash, nausea, and diarrhea. Results from in vitro studies suggested that PSA is not a good marker of sorafenib activity. The geometric mean exposure (AUC0-12) and maximum concentration (Cmax) were 9.76 h mg/L and 1.28 mg/L, respectively. The time to maximum concentration (tmax) and accumulation ratio (after second dose) ranged from 2 to 12 h and 0.68 to 6.43, respectively. Conclusions: Sorafenib is relatively well tolerated in AIPC with two patients showing evidence of improved bony metastatic lesions. Interpretation of this study is complicated by discordant radiographic and PSA responses. PSA may not be an adequate biomarker for monitoring sorafenib activity. Based on these observations, further investigation using only clinical and radiographic end points as progression criteria is warranted. Accrual to the second stage of trial is ongoing.
Glucocorticoids in the treatment of early and late RA
Authors: J W J Bijlsma
Journal: Annals of the Rheumatic Diseases (2003)

A little GC, like a glass of wine, may benefit many people, whereas a high dose of GC, like a bottle of wine, is harmful to all A t the 2003 meeting of the American College of Rheumatology (ACR) a debate on the advantages and disadvantages of glucocorticoids (GCs) in the treatment of early and late rheumatoid arthritis (RA) was held, with some authors putting the case for, and others the case against, such treatment (presentations now available online: http:// www.rheumatology.org).Some new data emerged, and this paper summarises the arguments and the existing and new data.
Aetiology of handball injuries: a case--control study.
Authors: M Dirx, L M Bouter, G H de Geus
Journal: British Journal of Sports Medicine (1992)

This article presents the results of a case--control study regarding the background to handball injuries among players of 12 years and older. Data were collected by means of a written questionnaire on the nature, location and direct causes of the injuries as well as information on risk factors. Injured players (n = 130) are compared with non-injured players (n = 512). The response for the cases was 67% and for the controls 75%. These injuries are frequently located at the lower extremities (54% of injuries), especially the ankle, and the majority involve distortions (35%) and strains (26%). Players greater than 20 years have a significantly greater risk of injury than players less than 20 years (odds ratio 1.9). Several factors seem to increase the injury risk, although not significantly: having greater than 5 years experience, not doing stretching exercises and not wearing tape or bandages. Another factor, not wearing elbow protectors, appears to decrease the injury risk significantly. It is advisable to interpret the results of this study with some caution, as selection and information bias might have influenced the validity to some extent. Furthermore, the reliability of the data is limited due to the relatively small number of injured players in the study. Some guidelines for future studies are formulated.
Respiratory Syncytial Virus Increases the Virulence of <i>Streptococcus pneumoniae</i> by Binding to Penicillin Binding Protein 1a. A New Paradigm in Respiratory Infection
Authors: Claire M. Smith, Sara Sandrini, Sumit Datta, Primrose Freestone, Sulman Shafeeq, Priya Radhakrishnan, Gwyneth Williams, Sarah M. Glenn, Oscar P. Kuipers, Robert A. Hirst, Andrew J. Easton, Peter W. Andrew, Christopher O’Callaghan
Journal: American Journal of Respiratory and Critical Care Medicine (2014)

Respiratory syncytial virus (RSV) and Streptococcus pneumoniae are major respiratory pathogens. Coinfection with RSV and S. pneumoniae is associated with severe and often fatal pneumonia but the molecular basis for this remains unclear.To determine if interaction between RSV and pneumococci enhances pneumococcal virulence.We used confocal microscopy and Western blot to identify the receptors involved in direct binding of RSV and pneumococci, the effects of which were studied in both in vivo and in vitro models of infection. Human ciliated respiratory epithelial cell cultures were infected with RSV for 72 hours and then challenged with pneumococci. Pneumococci were collected after 2 hours exposure and changes in gene expression determined using quantitative real-time polymerase chain reaction.Following incubation with RSV or purified G protein, pneumococci demonstrated a significant increase in the inflammatory response and bacterial adherence to human ciliated epithelial cultures and markedly increased virulence in a pneumonia model in mice. This was associated with extensive changes in the pneumococcal transcriptome and significant up-regulation in the expression of key pneumococcal virulence genes, including the gene for the pneumococcal toxin, pneumolysin. We show that mechanistically this is caused by RSV G glycoprotein binding penicillin binding protein 1a.The direct interaction between a respiratory virus protein and the pneumococcus resulting in increased bacterial virulence and worsening disease outcome is a new paradigm in respiratory infection.