tbuckley/cabot-search huggingface dataset:
Outpatient management of primary spontaneous pneumothorax: a prospective study
Authors: Massongo Massongo, Sylvie Leroy, Arnaud Scherpereel, Fabien Vaniet, Xavier Dhalluin, Bachar Chahine, Céline Sanfiorenzo, Michaël Genin, Charles-Hugo Marquette
Journal: European Respiratory Journal (2013)

We prospectively assessed the safety and cost saving of a small-bore drain based procedure for outpatient management of first episodes of primary spontaneous pneumothorax. Patients were managed by observation alone or insertion of an 8.5-F “pig-tail” drain connected to a one-way valve, according to size and clinical tolerance of the pneumothorax. All patients were reassessed after 4 h, on the first working day after discharge and on day 7. Patients still exhibiting air leak on day 4 underwent thoracoscopy. The primary end-point was complete lung re-expansion at day 7. 60 consecutive patients entered the study. 48 (80%) met the definition of large pneumothorax. The success rate was 83%. The 1-year recurrence rate was 17%. 36 (60%) patients were discharged after 4 h and 50% had full outpatient management. No severe complication was observed. The mean± sd length of hospitalisation was 2.3±3.1 days. This policy resulted in about a 40% reduction in hospital stay-related costs. The present study supports the use of a single system combined with a well-defined management algorithm including safe discharge criteria, as an alternative to manual aspiration or chest tube drainage. This approach participates in healthcare cost-savings.
How to treat children's pneumonia: a complex problem
Authors: M. Don, M. Korppi
Journal: European Respiratory Journal (2010)

How to treat children's pneumonia: a complex problemTo the Editors:We read with great interest the analysis of cost minimisation in the treatment of paediatric community-acquired pneumonia (CAP) by LORGELLY et al. [1] in the current issue of the European Respiratory Journal.The analysis was based on the randomised controlled non-blinded multicentre equivalence trial (PIVOT study), in which oral amoxicillin and intravenous benzyl penicillin had equivalent efficacy in the treatment of CAP in 246 children admitted to hospital [2].The median time for temperature to be ,38uC for 24 h was 1.23 days in the intravenous penicillin group and 1.30 days in the oral amoxicillin group [2].The median in-patient stay was significantly shorter in the oral amoxicillin group than in the intravenous penicillin group (1.77 versus 2.10 days, respectively).The PIVOT study did not take into account the aetiology or severity of CAP, or the age of the patients.The high levels of nonspecific inflammation markers suggested that most patients had either bacterial or mixed viral-bacterial CAP.Children with complicated pneumonia, such as those with oxygen saturation ,85%, shock requiring fluid resuscitation or pleural fluid requiring drainage, were excluded [2].
Early Management of Laryngeal Injuries
Authors: A G D Maran, J A M Murray, P M Stell, A Tucker
Journal: Journal of the Royal Society of Medicine (1981)

The results of acute laryngeal trauma sustained by 44 patients are reported. Three major aetiological groups are identified: road traffic accidents, blunt injury and penetrating injury. Road traffic accidents appear to produce severe injury, but the long-term follow-up results are similar to those laryngeal injuries which were not recognized initially and who developed a chronic stenosis. The blunt injury group sustained less forceful trauma; 14 of the 18 were treated conservatively and all patients had a good result. The majority of the penetrating injury group developed good breathing and a good voice following operation. Some of the technical expertise normally used to treat chronic laryngeal stenosis has been included in this series to good effect.
Clinical Definition of Acquired Resistance to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Non–Small-Cell Lung Cancer
Authors: David Jackman, William Pao, Gregory J. Riely, Jeffrey A. Engelman, Mark G. Kris, Pasi A. Jänne, Thomas Lynch, Bruce E. Johnson, Vincent A. Miller
Journal: Journal of Clinical Oncology (2009)

Ten percent of North American patients with non-small-cell lung cancer have tumors with somatic mutations in the gene for the epidermal growth factor receptor (EGFR). Approximately 70% of patients whose lung cancers harbor somatic mutations in exons encoding the tyrosine kinase domain of EGFR experience significant tumor regressions when treated with the EGFR tyrosine kinase inhibitors (TKIs) gefitinib or erlotinib. However, the overwhelming majority of these patients inevitably acquire resistance to either drug. Currently, the clinical definition of such secondary or acquired resistance is not clear. We propose the following criteria be used to define more precisely acquired resistance to EGFR TKIs. All patients should have the following criteria: previous treatment with a single-agent EGFR TKI (eg, gefitinib or erlotinib); either or both of the following: a tumor that harbors an EGFR mutation known to be associated with drug sensitivity or objective clinical benefit from treatment with an EGFR TKI; systemic progression of disease (Response Evaluation Criteria in Solid Tumors [RECIST] or WHO) while on continuous treatment with gefitinib or erlotinib within the last 30 days; and no intervening systemic therapy between cessation of gefitinib or erlotinib and initiation of new therapy. The relatively simple definition proposed here will lead to a more uniform approach to investigating the problem of acquired resistance to EGFR TKIs in this unique patient population. These guidelines should minimize reporting of false-positive and false-negative activity in these clinical trials and would facilitate the identification of agents that truly overcome acquired resistance to gefitinib and erlotinib.
Dr. Turecki and Colleagues Reply
Authors: GUSTAVO TURECKI, RICHARD BRIÈRE, KAREN DEWAR, ALAIN LESAGE, MONIQUE SÉGUIN, NADIA CHAWKY, CLAUDE VANIER, MARTIN ALDA, RIDHA JOOBER, CHAWKI BENKELFAT, GUY A. ROULEAU
Journal: American Journal of Psychiatry (2000)
Obesity, Weight Gain, and Risk of Biochemical Failure among Prostate Cancer Patients following Prostatectomy
Authors: Sara S. Strom, Xuemei Wang, Curtis A. Pettaway, Christopher J. Logothetis, Yuko Yamamura, Kim-Anh Do, Richard J. Babaian, Patricia Troncoso
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Several lines of evidence suggest that diet and weight gain may be important environmental factors implicated in prostate carcinogenesis, especially in tumor progression. The purpose of this study was to evaluate obesity at different ages in a well-characterized cohort of prostate cancer patients treated with prostatectomy and to develop a prognostic model that incorporates body mass index (BMI) as a measure of obesity. Experimental Design: We carried out a prospective study of 526 patients registered at the M.D. Anderson Cancer Center from 1992 to 2001. Kaplan-Meier and Cox proportional hazard analyses were done. Results: During an average follow-up of 54 months, 97 (18%) post-prostatectomy patients experienced biochemical failure. Patients who were obese (BMI ≥ 30 kg/m2) at diagnosis had a higher rate of biochemical failure than nonobese men (P = 0.07). Those obese at 40 years had an even greater rate of biochemical failure (P = 0.001). Higher BMI at diagnosis [hazard ratio (HR), 1.07; P = 0.01] and Gleason score = 7(4 + 3) and ≥8 (HR, 3.9; P = 0.03 and HR, 10.0; P ≤ 0.001, respectively) remained significant independent predictors of biochemical failure in multivariate analysis. Men who gained weight at the greatest rate (&amp;gt;1.5 kg/y) between 25 years and diagnosis progressed significantly sooner (mean time, 17 months) than those who exhibited a slower weight gain (mean time, 39 months; Ptrend = 0.005). The inclusion of obesity to the clinical nomogram improved performance. Conclusions: Our findings validate the importance for a role of obesity in prostate cancer progression and suggest a link to the biological basis of prostate cancer progression that can be therapeutically exploited.
Platelet-derived growth factor expression in primary pulmonary hypertension: comparison of HIV seropositive and HIV seronegative patients
Authors: M Humbert, G Monti, M Fartoukh, A Magnan, F Brenot, B Rain, F Capron, P Galanaud, P Duroux, G Simonneau, D Emilie
Journal: European Respiratory Journal (1998)

Primary pulmonary hypertension (PPH) is characterized by intimal fibrosis and cell proliferation (including fibroblasts, smooth muscle and endothelial cells) in the distal pulmonary arterial tree. Considerable interest has been generated by recent reports of PPH in human immunodeficiency virus (HIV)-1-infected individuals. Although the lack of evidence for a pulmonary artery infection has suggested that in such cases HIV may act through mediator release rather than by direct endothelial infection, the mechanisms underlying HIV-associated PPH remain poorly defined. Platelet-derived growth factor (PDGF) has the ability to induce smooth muscle cell and fibroblast proliferation and migration. Given these considerations, we have attempted to document a possible role for PDGF in PPH occurring in HIV seropositive and seronegative patients. Using semiquantitative polymerase chain reaction (PCR), PDGF A-chain messenger ribonucleic acid (mRNA) expression was analysed in surgical lung biopsies from 13 HIV seronegative patients and one HIV seropositive patient, all displaying severe PPH. In parallel, lung samples from two patients with HIV-1-associated PPH were studied by immunohistochemistry and in situ hybridization. Results were compared to those obtained in three HIV-1-infected individuals with no pulmonary complication (as demonstrated by clinical, radiological, bacteriological, and necropsy findings) and five control lung biopsies. As compared to controls, PDGF A-chain mRNA expression is elevated in lung biopsies from patients displaying PPH (p=0.029). In HIV-1-associated PPH, interstitial perivascular cells expressing PDGF A-chain mRNA and protein could be detected by in situ hybridization and immunohistochemistry, respectively. Platelet-derived growth factor expression is elevated in lung biopsies of patients displaying primary pulmonary hypertension. Growth factors such as platelet-derived growth factor may play a part in the initiation and/or progression of primary pulmonary hypertension.
Risk of new or recurrent cancer under immunosuppressive therapy in patients with IBD and previous cancer
Authors: Laurent Beaugerie, Fabrice Carrat, Jean-Frédéric Colombel, Anne-Marie Bouvier, Harry Sokol, Abdenour Babouri, Franck Carbonnel, David Laharie, Jean-Luc Faucheron, Tabassome Simon, Aimery de Gramont, Laurent Peyrin-Biroulet
Journal: Gut (2013)

<h3>Objective</h3> To explore the risk of new or recurrent cancer among patients with IBD and previous cancer, exposed or not to immunosuppressants. <h3>Design</h3> Among the 17 047 patients of the CESAME prospective observational cohort who were enrolled from May 2004 to June 2005, and followed-up until December 2007, we identified 405 patients with cancer diagnosed previous to study entry. We calculated the rates of incident cancer in patients with or without previous cancer, and we assessed by survival analysis and nested case-control study the impact of immunosuppressants on the risk of incident new or recurrent cancer in patients with previous cancer. <h3>Results</h3> The rate of incident cancer was 21.1/1000 patient-years (PY) and 6.1/1000 PY in patients with and without previous cancer, respectively. The multivariate-adjusted HR of incident cancer between patients with and without previous cancer was 1.9 (95% CI 1.2 to 3.0, p=0.003). Among patients with previous cancer, the rates of new and recurrent cancers were, respectively, 13.2/1000 PY and 6.0/1000 PY in the 312 patients who were not taking immunosuppressant at the time of study entry, and 23.1/1000 PY and 3.9/1000 PY in the 93 patients treated with immunosuppressants at study entry. There was no significant association between the exposure to immunosuppressants and the risk of new or recurrent cancer. <h3>Conclusions</h3> Patients with IBD with a history of cancer are at increased risk of developing any (new or recurrent) cancer, with a predominant incidence of new cancers. Treatment with immunosuppressants has no overall major impact per se on this risk.
How Can We Increase Translation of Research into Practice? Types of Evidence Needed
Authors: Russell E. Glasgow, Karen M. Emmons
Journal: Annual Review of Public Health (2006)

This review summarizes key factors that have interfered with translation of research to practice and what public health researchers can do to hasten such transfer, focusing on characteristics of interventions, target settings, and research designs. The need to address context and to utilize research, review, and reporting practices that address external validity issues-such as designs that focus on replication, and practical clinical and behavioral trials-are emphasized. Although there has been increased emphasis on social-ecological interventions that go beyond the individual level, interventions often address each component as if it were an independent intervention. Greater attention is needed to connectedness across program levels and components. Finally, examples are provided of evaluation models and current programs that can help accelerate translation of research to practice and policy.
Selective apoptosis of CD4+CD8+ thymocytes by the anti-Fas antibody.
Authors: J Ogasawara, T Suda, S Nagata
Journal: The Journal of Experimental Medicine (1995)

Fas is a cell surface protein that mediates apoptosis. A mouse mutant, lpr (lymphoproliferation), has a mutation in the Fas gene. In this report, we studied the expression and function of Fas in various subpopulations of mouse thymocytes. Abundant expression of Fas was detected on CD4+CD8+ double positive as well as CD4+ or CD8+ single positive thymocytes in wild-type mice. Little or low levels of Fas were expressed in CD4-CD8- double negative thymocytes except for the CD4-CD8-CD3+ phenotype, which expresses Fas as abundantly as double positive or single positive subsets. On the other hand, no Fas expression was detected in any population of thymocytes from lpr mice. When the wild-type thymocytes were treated with the agonistic anti-Fas antibody, double positive cells from the wild-type mice were selectively killed by apoptosis, whereas, the single positive cells were resistant to its cytolytic activity despite their abundant expression of Fas. Unlike the apoptosis of thymocytes induced by glucocorticoid or T cell activator, the Fas-induced apoptosis of thymocytes was enhanced by metabolic inhibitors such as cycloheximide. Furthermore, intraperitoneal administration of the anti-Fas antibody into mice caused rapid apoptosis of thymocytes in vivo.
Linking restless legs syndrome with Parkinson's disease: clinical, imaging and genetic evidence
Authors: Tasneem Peeraully, Eng-King Tan
Journal: Translational Neurodegeneration (2012)

Restless legs syndrome (RLS) and Parkinson's disease (PD) are both common neurological disorders. There has been much debate over whether an etiological link between these two diseases exists and whether they share a common pathophysiology. Evidence pointing towards a link includes response to dopaminergic agents in PD and RLS, suggestive of underlying dopamine dysfunction in both conditions. The extrastriatal dopaminergic system, in particular altered spinal dopaminergic modulation, may be variably involved in PD patients with RLS symptoms. In addition, there is now evidence that the nigrostriatal system, primarily involved in PD, is also affected in RLS. Furthermore, an association of RLS with the parkin mutation has been suggested. The prevalence of RLS has also been reported to be increased in other disorders of dopamine regulation. However, clinical association studies and functional imaging have produced mixed findings. Conflicting accounts of emergence of RLS and improvement in RLS symptoms after deep brain stimulation (DBS) also contribute to the uncertainty surrounding the issue. Among the strongest arguments against a common pathophysiology is the role of iron in RLS and PD. While elevated iron levels in the substantia nigra contribute to oxidative stress in PD, RLS is a disorder of relative iron deficiency, with symptoms responding to replacement therapy. Recent ultrasonography studies have suggested that, despite overlapping clinical features, the mechanisms underlying idiopathic RLS and RLS associated with PD may differ. In this review, we provide a concise summary of the clinical, imaging and genetic evidence exploring the link between RLS and PD.
A Phase I, Open-Label Study of Siltuximab, an Anti–IL-6 Monoclonal Antibody, in Patients with B-cell Non-Hodgkin Lymphoma, Multiple Myeloma, or Castleman Disease
Authors: Razelle Kurzrock, Peter M. Voorhees, Corey Casper, Richard R. Furman, Luis Fayad, Sagar Lonial, Hossein Borghaei, Sundar Jagannath, Lubomir Sokol, Saad Z. Usmani, Helgi van de Velde, Xiang Qin, Thomas A. Puchalski, Brett Hall, Manjula Reddy, Ming Qi, Frits van Rhee
Journal: Clinical Cancer Research (2013)

To evaluate the safety and pharmacokinetics of siltuximab, an anti-interleukin-6 chimeric monoclonal antibody (mAb) in patients with B-cell non-Hodgkin lymphoma (NHL), multiple myeloma, or Castleman disease.In an open-label, dose-finding, 7 cohort, phase I study, patients with NHL, multiple myeloma, or symptomatic Castleman disease received siltuximab 3, 6, 9, or 12 mg/kg weekly, every 2 weeks, or every 3 weeks. Response was assessed in all disease types. Clinical benefit response (CBR; composite of hemoglobin, fatigue, anorexia, fever/night sweats, weight, largest lymph node size) was also evaluated in Castleman disease.Sixty-seven patients received a median of 16 siltuximab doses for a median of 8.5 (maximum 60.5) months; 29 were treated 1 year or longer. There was no dose-limiting toxicity, antibodies to siltuximab, or apparent dose-toxicity relationship. The most frequently reported possible drug-related adverse events were thrombocytopenia (25%), hypertriglyceridemia (19%), neutropenia (19%), leukopenia (18%), hypercholesterolemia (15%), and anemia (10%). None of these events led to dose delay/discontinuation except for neutropenia and thrombocytopenia (n = 1 each). No treatment-related deaths occurred. C-reactive protein (CRP) suppression was most pronounced at 12 mg/kg every 3 weeks. Mean terminal-phase half-life of siltuximab ranged 17.73 to 20.64 days. Thirty-two of 37 (86%) patients with Castleman disease improved in 1 or more CBR component; 12 of 36 evaluable Castleman disease patients had radiologic response [complete response (CR), n = 1; partial response (PR), n = 11], including 8 of 19 treated with 12 mg/kg; 2 of 14 (14%) evaluable NHL patients had PR; 2 of 13 (15%) patients with multiple myeloma had CR.No dose-related or cumulative toxicity was apparent across all disease indications. A dose of 12 mg/kg every 3 weeks was recommended on the basis of the high response rates in Castleman disease and the sustained CRP suppression. Randomized studies are ongoing in Castleman disease and multiple myeloma.
Distinct structural compartmentalization of the signal transducing functions of major histocompatibility complex class II (Ia) molecules.
Authors: P André, J C Cambier, T K Wade, T Raetz, W F Wade
Journal: The Journal of Experimental Medicine (1994)

Class II major histocompatibility complex encoded proteins (MHC class II or Ia molecules) are principal plasma membrane proteins involved in activation of both B and T cells during antigen-driven immune responses. Recent data indicate that class II molecules are more than simply recognition elements that provide a ligand for the T cell antigen receptor. Changes in B cell physiology that follow class II binding are now recognized as being required not only for the induction of T cell activation, but also for B cell activation and proliferation. It is interesting to note that class II molecules appear to transduce signals via two distinct mechanisms depending upon the differentiative state of the B cell on which they are expressed. While one of these pathways, involving cAMP generation and protein kinase C localization in the cytoskeletal/nuclear compartment, is seen in resting B cells, the second is seen in primed B cells and involves tyrosine kinase activation, inositol lipid hydrolysis, and Ca2+ mobilization. Use of this pathway is correlated with ability of class II to transduce signals leading to B cell proliferation. To begin to address the molecular basis of this unique, activation-dependent, differential coupling of class II to signaling pathways, we conducted mutational analysis of class II structural requirements for signal transduction. Here we report that the cytoplasmic (Cy) domains of I-Ak class II molecules are not required for either receptor-mediated activation of protein tyrosine phosphorylation or Ca2+ mobilization. This is in contrast to the requirement of the Cy domain of beta chain of class II for the alternate signaling pathway and efficient antigen presentation to autoreactive T cell lines. Disparate distribution of functional motifs within the MHC class II molecules may reflect use of distinct receptor associated effector molecules to sustain different modes of signal transduction in various class II-expressing cells.
A Century of Tuberculosis
Authors: John F. Murray
Journal: American Journal of Respiratory and Critical Care Medicine (2004)

Here are the facts: during the last 100 years in the thousands of years-long history of tuberculosis, we have benefited from unquestioned scientific and clinical progress; but at the same time we have witnessed a global increase in the number of victims and a worsening of the efficacy of control manifested by a rising prevalence of drug resistance in many countries. Today, tuberculosis is relatively easy to diagnose; when the right combination of medications is made available and taken by the patient, the disease can be cured more than 95% of the time; and in certain targeted populations, the manifestations of the disease can be attenuated by vaccination and even prevented by chemotherapy. Despite these remarkable achievements, the estimated number of new cases of tuberculosis in the world during each of the last several years has steadily increased: from 8.0 million in 1997 to 8.3 million in 2000, and is expected to reach 10.2 million in 2005 (1, 2). There are more people infected with Mycobacterium tuberculosis in the world this year than ever before, and from 1997 through 2000 the number of new cases of tuberculosis and the per capita incidence worldwide rose 1.8% per year and 0.4% per year, respectively (2). Although the overall global tuberculosis situation is deteriorating, it is actually improving in some countries. In the United States, for example, the incidence of newly reported cases of tuberculosis has fallen steadily since 1992 to its lowest level ever, and in 2002 (last report) was 5.2/100,000 population (3)—a stunning public health accomplishment. Such impressive progress, however, is found only in rich (industrialized) nations, although problems remain in many of their marginalized innercity communities; moreover, the reverse is occurring in many poor (developing) countries, which is where the great majority, 86%, of the world’s total population live. And not only are these destitute regions home to 95% of all the world’s cases of active tuberculosis and 98% of the nearly 2 million deaths from the disease each year, exactly the same countries are now being ravaged by the pandemic of human immunodeficiency virus (HIV) infection—the most powerful factor ever known to favor the development of tuberculosis (4). This historical review examines the century-long paradox of tuberculosis and illustrates an important point made by others (5): the conquest of tuberculosis by medical advances alone will never occur until the prevailing global inequities of wealth and health care are corrected.