tbuckley/cabot-search huggingface dataset:
Neuropeptide Y and Leptin in Patients with Obstructive Sleep Apnea Syndrome
Authors: Antonia Barceló, Ferran Barbé, Elena Llompart, Mónica de la Peña, Joaquin Durán-Cantolla, Antoni Ladaria, Margalida Bosch, Lourdes Guerra, Alvar G. N. Agustí
Journal: American Journal of Respiratory and Critical Care Medicine (2004)

Neuropeptide Y (NPY) and leptin are two peptides involved in the regulation of body weight, energy balance, and sympathetic tone. This study investigates the independent role of apneas and obesity on NPY and leptin plasma levels in patients with obstructive sleep apnea syndrome (OSAS). To this end we compared their values in 23 obese (body mass index > 30 kg/m2) and 24 nonobese (body mass index < 27 kg/m2) patients with OSAS, and in 19 obese and 18 nonobese control subjects without OSAS. Patients who used continuous positive airway pressure for more than 4 hours/night were reexamined 3 and 12 months later. We found that NPY levels were increased (p < 0.01) in patients with OSAS independently of obesity. Leptin levels were also increased in OSAS but this was mostly associated to obesity. Continuous positive airway pressure treatment reduced NPY levels in all patients and leptin levels only in nonobese patients (p < 0.01). We concluded that NPY and leptin plasma levels are increased in patients with OSAS. Yet, whereas the former appear independent of obesity, the latter are mostly associated with obesity.
High–Dose Pulse Versus Nonpulse Corticosteroid Regimens in Severe Acute Respiratory Syndrome
Authors: James C. Ho, Gaik C. Ooi, Thomas Y. Mok, Johnny W. Chan, Ivan Hung, Bing Lam, Poon C. Wong, Patrick C. Li, Pak L. Ho, Wah K. Lam, Chun K. Ng, Mary S. Ip, Kar N. Lai, Moira Chan-Yeung, Kenneth W. Tsang
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

The treatment of atypical pneumonia, subsequently termed severe acute respiratory syndrome (SARS), is controversial, and the efficacy of corticosteroid therapy is unknown. We have evaluated the clinical and radiographic outcomes of 72 patients with probable SARS (median age 37 years, 30 M), who received ribavirin and different steroid regimens in two regional hospitals. Chest radiographs were scored according to the percentage of lung field involved. Seventeen patients initially received pulse steroid (PS) (methylprednisolone ⩾ 500 mg/day) and 55 patients initially received nonpulse steroid (NPS) (methylprednisolone < 500 mg/day) therapy. The cumulative steroid dosage; intensive care unit admission, mechanical ventilation, and mortality rates; and hematologic and biochemical parameters were similar in both groups after 21 days. However, patients in the PS group had less oxygen requirement, better radiographic outcome, and less likelihood of requiring rescue PS therapy than their counterparts. There was no significant difference between the two groups in hemolytic anemia, severe secondary infections, or hematemesis, but patients in the PS group had less hyperglycaemia. Initial use of pulse methylprednisolone therapy appears to be a more efficacious and an equally safe steroid regimen when compared with regimens with lower dosage and should be considered as the preferred steroid regimen in the treatment of SARS, pending data from future randomized controlled trials.
Molecular Pathways: Targeting Inhibitor of Apoptosis Proteins in Cancer—From Molecular Mechanism to Therapeutic Application
Authors: Simone Fulda
Journal: Clinical Cancer Research (2013)

Inhibitor of apoptosis (IAP) proteins play a critical role in the control of survival and cell death by regulating key signaling events such as caspase activation and NF-κB signaling. Because aberrantly high expression of IAP proteins represents a frequent oncogenic event in human cancers, therapeutic targeting of IAP proteins is considered as a promising approach. Several small-molecule pharmacologic inhibitors of IAP proteins that mimic the binding domain of the endogenous IAP antagonist second mitochondrial activator of caspases (Smac) to IAP proteins have been developed over the past few years. IAP antagonists have been shown in various preclinical cancer models to either directly initiate cell death or, alternatively, to prime cancer cells for cytotoxic therapies by lowering the threshold for cell death induction. IAP antagonists (i.e., GDC-0917/CUDC-427, LCL161, AT-406, HGS1029, and TL32711) are currently under evaluation in early clinical trials alone or in combination regimens. Thus, the concept to therapeutically target IAP proteins in human cancer has in principle been successfully transferred into a clinical setting and warrants further evaluation as a treatment approach.
Adjuvant Immunotherapy of Patients With High-Risk Melanoma Using Vaccinia Viral Lysates of Melanoma: Results of a Randomized Trial
Authors: Peter Hersey, Alan S. Coates, William H. McCarthy, John F. Thompson, Robert W. Sillar, Roderick McLeod, P. Grantley Gill, Brendon J. Coventry, Amanda McMullen, Haryana Dillon, R. John Simes
Journal: Journal of Clinical Oncology (2002)

Patients with high-risk melanoma treated by immunotherapy with vaccinia viral lysates were found in phase II studies to have improved survival compared with historical controls. We therefore elected to test this therapy in a phase III study.A prospective, randomized, multicenter trial to determine whether immunotherapy with a vaccine prepared from vaccinia melanoma cell lysates (VMCL) over a 2-year period after definitive surgery would improve relapse-free survival (RFS) and overall survival (OS) in patients with American Joint Committee on Cancer stage IIB and III melanoma compared with a control group treated only with surgery.A total of 700 patients were randomized: 353 to VMCL and 347 to no immunotherapy. Seventy-seven percent had lymph node (LN) metastases and 66% had clinically detected LN metastases. Analysis on the basis of all eligible, randomized patients (n = 675) found, after a median follow-up period of 8 years, a median OS of 88 months in the control versus 151 months in the treated group (hazard ratio [HR], 0.81; 95% confidence interval [CI], 0.64 to 1.02; P =.068 by stratified univariate Cox analysis). At 5 and 10 years, survival rates for control and treated patients were 54.8% v 60.6% and 41% v 53.4%, respectively. Median RFS was 43 months in the control group compared with 83 months in the treated group (HR, 0.86; 95% CI, 0.7 to 1.07; P =.17). RFS at 5 years was 50.9% for the treated group and 46.8% for the control group. There were no selective benefits from the vaccine for particular subsets of patients.Immunotherapy with VMCL was not associated with a statistically significant improvement in OS or RFS, with CIs not ruling out important gains from such treatment.
Glycated Hemoglobin and Risk of Hypertension in the Atherosclerosis Risk in Communities Study
Authors: Julie K. Bower, Lawrence J. Appel, Kunihiro Matsushita, J. Hunter Young, Alvaro Alonso, Frederick L. Brancati, Elizabeth Selvin
Journal: Diabetes Care (2012)

OBJECTIVE Diabetes and hypertension often co-occur and share risk factors. Hypertension is known to predict diabetes. However, hyperglycemia also may be independently associated with future development of hypertension. We investigated glycated hemoglobin (HbA1c) as a predictor of incident hypertension. RESEARCH DESIGN AND METHODS We conducted a prospective analysis of 9,603 middle-aged participants in the Atherosclerosis Risk in Communities Study without hypertension at baseline. Using Cox proportional hazards models, we estimated the association between HbA1c at baseline and incident hypertension by two definitions 1) self-reported hypertension during a maximum of 18 years of follow-up and 2) measured blood pressure or hypertension medication use at clinic visits for a maximum of 9 years of follow-up. RESULTS We observed 4,800 self-reported and 1,670 visit-based hypertension cases among those without diagnosed diabetes at baseline. Among those with diagnosed diabetes at baseline, we observed 377 self-reported and 119 visit-based hypertension cases. Higher baseline HbA1c was associated with an increased risk of hypertension in subjects with and without diabetes. Compared with nondiabetic adults with HbA1c &amp;lt;5.7%, HbA1c in the prediabetic range (5.7–6.4%) was independently associated with incident self-reported hypertension (hazard ratio 1.14 [95% CI 1.06–1.23]) and visit-detected hypertension (1.17 [1.03–1.33]). CONCLUSIONS We observed that individuals with elevated HbA1c, even without a prior diabetes diagnosis, are at increased risk of hypertension. HbA1c is a known predictor of incident heart disease and stroke. Our results suggest that the association of HbA1c with cardiovascular risk may be partially mediated by the development of hypertension.
Design of a protocol for large-scale epidemiological studies in individual sports: the Swedish Athletics injury study
Authors: Jenny Jacobsson, Toomas Timpka, Joakim Ekberg, Jan Kowalski, Sverker Nilsson, Per Renström
Journal: British Journal of Sports Medicine (2010)

Background Epidemiological studies have mainly been performed on team sports. The authors set out to develop a protocol for large-scale epidemiological studies of injuries among elite athletics athletes. Methods An argument-based method for investigation of complex design problems was used to structure the collection and analysis of data. Specification of the protocol was preceded by an examination of requirements on injury surveillance in individual sports and iterated drafting of protocol specifications, and followed by formative evaluations. Results The requirements analysis shows that the central demand on the protocol is to allow for detailed epidemiological analyses of overuse injuries, which subsequently requires regular collection of self-reported data from athletes. The resulting study protocol is centred on a web-based weekly athlete e-diary enabling continual collection of individual-level data on exposure and injuries. To be able to interpret the self-reported data on injury events, collection of a wide range of personal baseline data from the athlete, including a psychological profile, is included in the protocol. Conclusions The resulting protocol can be employed in intervention programmes that can prevent suffering among both adult elite and youth talent athletes who have made considerable life investments in their sport.
House Dust Mites Induce Proliferation of Severe Asthmatic Smooth Muscle Cells via an Epithelium-Dependent Pathway
Authors: Thomas Trian, Benoit Allard, Isabelle Dupin, Gabrielle Carvalho, Olga Ousova, Elise Maurat, Jehan Bataille, Matthieu Thumerel, Hugues Begueret, Pierre-Olivier Girodet, Roger Marthan, Patrick Berger
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

Asthma is a frequent airway disease, and asthma control determinants have been associated with indoor allergen sensitization. The most frequent allergens are house dust mites (HDM), which act in vivo on the bronchial epithelial layer. Severe asthma has also been associated with bronchial remodeling and more specifically with increased mass of bronchial smooth muscle (BSM). However, the relationship between HDM stimulation of the bronchial epithelial layer and BSM remodeling is unknown.To evaluate whether epithelial stimulation with HDM induces BSM cell proliferation in subjects with severe asthma.A total of 22 subjects with severe asthma and 27 subjects with no asthma were recruited. We have developed an in vitro culture model combining an epithelium layer in air-liquid interface (ALI) interacting with BSM. We assessed BSM proliferation using BrdU incorporation. We explored the role of epithelium-derived mediators using reverse-transcriptase polymerase chain reaction (RT-PCR) and ELISA in vitro and in vivo. Finally, leukotrienes receptor expression was assessed in vitro by flow cytometry and RT-PCR and ex vivo by laser microdissection and RT-PCR.We found that epithelial stimulation by HDM selectively increased the proliferation of asthmatic BSM cells and not that of nonasthmatic cells. The mechanism involved epithelial protease-activated receptor-2-dependent production of leukotrienes C4 associated with an overexpression of leukotrienes receptor CysLTR1 by asthmatic BSM cells in vitro and ex vivo.This work demonstrates the selective role of HDM on BSM remodeling in patients with severe asthma and points out different therapeutic targets at epithelial and smooth muscle levels.
PMO-018 Dedicated specialist dietetic input improves outcomes for UGI surgical cancer patients
Authors: H L Webster
Journal: Gut (2012)

<h3>Introduction</h3> Upper GI (UGI) cancer patients are at high risk of malnutrition increasing risk of complications post-operatively. Surgeons and Oncologists at Ninewells Hospital, Dundee funded an UGI Oncology Dietitian who oversaw nutritional care of patients through neoadjuvant chemotherapy, preparation for surgery and into follow-up. Previously at Ninewells, dietetic care of patients was ad-hoc resulting in reduced nutritional status during chemotherapy, admissions for feeding and delays to surgery. Once the post-holder joined the MDT it was important to show value for money and clinical effectiveness so data were gathered on outcomes for patients who had undergone UGI cancer surgery in the year before the post-holder started (n=49) and for 1 year afterwards (n=22). <h3>Methods</h3> A literature search was performed using MEDLINE in order to compare results against other centres but no similar studies were found. Subsequently the MDT decided on clinical standards based on current evidence and acceptable limits including: Patients will be referred to the Upper GI Oncology Dietitian prior to surgery. Patients will maintain their weight during chemotherapy and surgical admissions within 5%. All patients will have a jejunostomy tube placed at the time of surgery. Data were gathered from medical and dietetic notes for each group on; whether patient was referred before surgery, weight (kg) at start and end of chemotherapy and on admission and discharge from surgery, whether jejunostomy placed at time of surgery, length of stay (LOS). <h3>Results</h3> <h3>Conclusion</h3> Results showed the positive and cost saving impact of a dedicated dietitian on standards measured especially during chemotherapy and on LOS. The number of feeding tubes inserted fell in the group with dietetic input reflecting the types of surgery performed. Improved communication and leadership between the dietitian and the MDT helped to prevent admissions for pre-operative feeding and reduce delays. Further large studies are required, particularly in the peri-operative period, to further promote dedicated dietetic input. <h3>Competing interests</h3> None declared.
Swift Development of Protective Effector Functions in Naive Cd8+ T Cells against Malaria Liver Stages
Authors: Gen-ichiro Sano, Julius C.R. Hafalla, Alexandre Morrot, Ryo Abe, Juan J. Lafaille, Fidel Zavala
Journal: The Journal of Experimental Medicine (2001)

We generated T cell receptor transgenic mice specific for the liver stages of the rodent malaria parasite Plasmodium yoelii and studied the early events in the development of in vivo effector functions in antigen-specific CD8+ T cells. Differently to activated/memory cells, naive CD8+ T cells are not capable of exerting antiparasitic activity unless previously primed by parasite immunization. While naive cells need to differentiate before achieving effector status, the time required for this process is very short. Indeed, interferon (IFN)-γ and perforin mRNA are detectable 24 h after immunization and IFN-γ secretion and cytotoxic activity are detected ex vivo 24 and 48 h after immunization, respectively. In contrast, the proliferation of CD8+ T cells begins after 24 h and an increase in the total number of antigen-specific cells is detected only after 48 h. Remarkably, a strong CD8+ T cell–mediated inhibition of parasite development is observed in mice challenged with viable parasites only 24 h after immunization with attenuated parasites. These results indicate that differentiation of naive CD8+ T cells does not begin only after extensive cell division, rather this process precedes or occurs simultaneously with proliferation.
Evidence for a critical contribution of pericytes in pulmonary arterial hypertension pathogenesis
Authors: Nicolas Ricard, Ly Tu, Alice Huertas, Carole Phan, Morane Le Hiress, Elie Fadel, Marc Humbert, Christophe Guignabert
Journal: European Respiratory Journal (2013)

Rationale: Pericytes and their crosstalk with endothelial cells (ECs) are critical for the development of a functional microvasculature and vascular remodeling. It is also known that pulmonary endothelial dysfunction is intertwined with the initiation and progression of pulmonary arterial hypertension (PAH).  Objectives: We hypothesized that pulmonary endothelial dysfunction, characterized by abnormal fibroblast growth factor (FGF)2 and interleukin (IL)-6 signaling, leads to abnormal microvascular pericyte coverage causing pulmonary arterial medial thickening.  Results: In human lung tissues, the number of pericytes is substantially increased (up to 2-fold) in distal PAH pulmonary arteries as compared to controls. Interestingly, in our murine retinal angiogenesis model, both FGF2 and IL-6 administration increased pericyte coverage. Furthermore, human pulmonary pericytes exhibit, in vitro, an accentuated proliferative and migratory response to conditioned media from human pulmonary idiopathic PAH (iPAH) ECs as compared to conditioned media from control ECs. Importantly, by using an anti-FGF2 neutralizing antibody, we attenuated these proliferative and migratory responses, whereas by using an anti-IL-6 neutralizing antibody, we decreased the migratory response without affecting the proliferative response. Finally, we found that both FGF2 and IL-6 affect the differentiation of pulmonary pericytes into contractile smooth muscle-like cells.  Conclusions: This is the first report of abnormal pericyte coverage in distal pulmonary arteries in human PAH. We are also showing that this phenomenon is directly linked with pulmonary endothelial dysfunction.
Development of Chest Pain in Munchausen's Syndrome
Authors: M. A. Peyman
Journal: BMJ (1960)

DIABETES MELLITUSBJoUNAL 699 oorderline cases of diabetes and will require careful follow-up.Of the other cases of non-diabetic glycosuria 25 were classified as renal glycosuria, 27 as transient glycosuria, seven were children and were unclassified, and nine did not have blood examinations performed.One case was found to have hyperglycaemia without glycosuria on a glucose-tolerance test.The significance of these cases is discussed, and it is concluded that all will require reassessment at a later date.The inference drawn from the study is that the number of undiagnosed diabetics present in the population is large enough to warrant the routine testing of urine for glucose, especially in the older age-groups.It is suggested that large-scale diabetes-detection drives should be started in this country on the same lines as in the United States.
A Bad Bug Takes on a New Role as a Cause of Ventilator-associated Pneumonia
Authors: Elias J. Anaissie
Journal: American Journal of Respiratory and Critical Care Medicine (2007)

Despite use of preventive strategies and significant advances in supportive care and antimicrobial therapy, ventilator-associated pneumonia (VAP) remains an important cause of morbidity and mortality (1). Although bacteria cause most VAPs, invasive pulmonary aspergillosis (IPA) is extremely uncommon, except when classical risk factors for aspergillosis (hematologic cancer, neutropenia, transplantation) are present. In this issue of the Journal (pp. 27‐34), Meersseman and colleagues (2) report their findings using detection of Aspergillus galactomannan (GM) (cell wall constituent released during tissue invasion) in bronchoalveolar lavage (BAL) fluid (BAL-GM) for diagnosing VAP caused by Aspergillus spp. Upon diagnosis of pneumonia, 110 adults at risk for IPA underwent BAL for culture and GM detection, serum GM, and chest computed tomography (CT). Only 22% of patients were neutropenic and 67% had underlying diseases other than hematologic cancer, including cirrhosis and chronic obstructive pulmonary disease (COPD). Twenty-six patients (24%) developed histopathologically proven IPA. The diagnostic sensitivity and specificity of BAL-GM was 88 and 87%, respectively, compared with 42% sensitivity for serum GM. Serum GM and BAL culture remained negative in 11 patients (42%) in whom BAL-GM was positive. Chest CT was of limited diagnostic value. The findings of this prospective study, backed by an impressive 95% autopsy rate, underscore the increasingly important role that Aspergillus species play as a cause of VAP in apparently immunocompetent intensive care unit (ICU) patients
Independent centromere formation in a capricious, gene-free domain of chromosome 13q21 in Old World monkeys and pigs.
Authors: Maria Francesca Cardone, Alicia Alonso, Michele Pazienza, Mario Ventura, Gabriella Montemurro, Lucia Carbone, Pieter J de Jong, Roscoe Stanyon, Pietro D'Addabbo, Nicoletta Archidiacono, Xinwei She, Evan E Eichler, Peter E Warburton, Mariano Rocchi
Journal: Genome biology (2006)

Abstract Background Evolutionary centromere repositioning and human analphoid neocentromeres occurring in clinical cases are, very likely, two stages of the same phenomenon whose properties still remain substantially obscure. Chromosome 13 is the chromosome with the highest number of neocentromeres. We reconstructed the mammalian evolutionary history of this chromosome and characterized two human neocentromeres at 13q21, in search of information that could improve our understanding of the relationship between evolutionarily new centromeres, inactivated centromeres, and clinical neocentromeres. Results Chromosome 13 evolution was studied, using FISH experiments, across several diverse superordinal phylogenetic clades spanning &gt;100 million years of evolution. The analysis revealed exceptional conservation among primates (hominoids, Old World monkeys, and New World monkeys), Carnivora (cat), Perissodactyla (horse), and Cetartiodactyla (pig). In contrast, the centromeres in both Old World monkeys and pig have apparently repositioned independently to a central location (13q21). We compared these results to the positions of two human 13q21 neocentromeres using chromatin immunoprecipitation and genomic microarrays. Conclusion We show that a gene-desert region at 13q21 of approximately 3.9 Mb in size possesses an inherent potential to form evolutionarily new centromeres over, at least, approximately 95 million years of mammalian evolution. The striking absence of genes may represent an important property, making the region tolerant to the extensive pericentromeric reshuffling during subsequent evolution. Comparison of the pericentromeric organization of chromosome 13 in four Old World monkey species revealed many differences in sequence organization. The region contains clusters of duplicons showing peculiar features.