tbuckley/cabot-search huggingface dataset:
A Pathologist’s View of Airway Obstruction in Chronic Obstructive Pulmonary Disease
Authors: James C. Hogg
Journal: American Journal of Respiratory and Critical Care Medicine (2012)

The boundary between purely conducting airways and gas exchanging tissue is formed by the terminal bronchioles as they divide into transitional bronchioles where alveolar openings first appear (1). The numbers of alveolar openings increase with each successive generation of branching until they take up the entire luminal surface in the alveolar ducts and the ducts branch for several more generations before ending blindly in alveolar sacs (2). McDonough and colleagues recently used a combination of multidetector computed tomography (MDCT) and micro-CT to show that there are about 44,510 ± 15,574 (± SD) terminal bronchioles/lung pair (3), a number that compares favorably to a mean of 44,500 ± 18,574 (± SD) obtained in four separate studies of individual lung casts (1, 4–6). Each terminal bronchiole supplies a unit of lung termed the acinus, and a secondary lobule refers to a group of acini that are either surrounded by a connective tissue septum (Figure 1A) when examined by histology (2), or where bronchioles cluster only millimeters apart (Figure 1B) when examined in a bronchogram (7).
Local anaesthesia for venous cannulation and arterial blood gas sampling: are doctors using it?
Authors: Daniel M Sado, Charles D Deakin
Journal: Journal of the Royal Society of Medicine (2005)

The pain of venous cannulation and arterial puncture can be greatly lessened by local anaesthesia. We sought information about the use of local anaesthesia for these procedures by doctors working in medicine, surgery and anaesthetics. A questionnaire was hand-delivered to 178 doctors in eight hospitals, all of whom responded. For insertion of large-bore cannulae, local anaesthesia was used by all the anaesthetists but less than half the medical and surgical doctors. For arterial blood sampling it was used by 60% of anaesthetists and 2% of ward doctors. Previous recommendations to use local anaesthesia seem to have been ignored, and in many instances these procedures are more painful than necessary.
Vitamin B<sub>12</sub>, Folate, and Homocysteine in Depression: The Rotterdam Study
Authors: Henning Tiemeier, H. Ruud van Tuijl, Albert Hofman, John Meijer, Amanda J. Kiliaan, Monique M.B. Breteler
Journal: American Journal of Psychiatry (2002)

The associations of vitamin B(12), folate, and homocysteine with depression were examined in a population-based study.The authors screened 3,884 elderly people for depressive symptoms. Subjects with positive screening results had psychiatric workups. Folate, vitamin B(12), and homocysteine blood levels were compared in 278 persons with depressive symptoms, including 112 with depressive disorders, and 416 randomly selected reference subjects. Adjustments were made for age, gender, cardiovascular disease, and functional disability.Hyperhomocysteinemia, vitamin B(12) deficiency, and to a lesser extent, folate deficiency were all related to depressive disorders. For folate deficiency and hyperhomocysteinemia, the association with depressive disorders was substantially reduced after adjustment for functional disability and cardiovascular disease, but for vitamin B(12) this appeared independent.The association of vitamin B(12) and folate with depressive disorders may have different underlying mechanisms. Vitamin B(12) may be causally related to depression, whereas the relation with folate is due to physical comorbidity.
Calculate the QT interval in patients taking drugs for dementia
Authors: Andrew Leitch, Peter McGinness, David Wallbridge
Journal: BMJ (2007)

A 76 year old woman was referred acutely after two syncopal episodes. She had a history of depression and Alzheimer's disease. No cardiac problems were reported. On admission her blood pressure was 160/112 mm Hg but she had a sinus bradycardia (42 beats/min) and the cardiac monitor showed paroxysmal ventricular tachycardia (torsade de pointes). The resting electrocardiogram showed gross prolongation of the QT segment (corrected QT interval 590-777 …
Glycine Antagonist in Neuroprotection for Patients With Acute Stroke
Authors: Ralph L. Sacco, Janet T. DeRosa, E. Clarke Haley, Jr, Bruce Levin, Paul Ordronneau, Stephen J. Phillips, Tanja Rundek, Rose G. Snipes, John L. P. Thompson, None for the GAIN Americas Investigators
Journal: JAMA (2001)

IN RECENT YEARS, CONSIDERABLE EFforts have been devoted to developing treatments aimed at restoring cerebral perfusion or limiting neuronal damage following acute ischemic stroke.Recognition of the "ischemic penumbra," a region of reduced cerebral blood flow in which cell death might be prevented, 1 has focused attention on treatments that might minimize or reverse brain damage when administered soon after stroke onset.Enlargement of infarct volume is determined by changes in metabolism caused by initiation of the ischemic cascade.This cascade involves energy supply failure, membrane depolarization, release of neurotransmitters (including glutamate in large amounts), accumulation of intracellular calcium, increased production of nitric oxide and free radicals, development of cellular edema, and finally, cell death. 2 Each step along the ischemic cascade offers a potential target for thera-
Intracytoplasmic sperm injection: a state of the art technique
Authors: R Mansour
Journal: Human Reproduction Update (1998)

Of the micromanipulation techniques developed in the twentieth century, intracytoplasmic sperm injection (ICSI) has been the major breakthrough in the field of assisted fertilization. This article reviews the indications for the use of ICSI, its clinical application, the establishment of an ICSI programme including protocol and the results obtained since the introduction of ICSI and the potential risks. In addition, intracytoplasmic spermatid injection is briefly discussed. Keywords:intracytoplasmic sperm injection/in-vitro fertilization
Effector memory T cell responses are associated with protection of rhesus monkeys from mucosal simian immunodeficiency virus challenge
Authors: Scott G Hansen, Cassandra Vieville, Nathan Whizin, Lia Coyne-Johnson, Don C Siess, Derek D Drummond, Alfred W Legasse, Michael K Axthelm, Kelli Oswald, Charles M Trubey, Michael Piatak, Jeffrey D Lifson, Jay A Nelson, Michael A Jarvis, Louis J Picker
Journal: Nature Medicine (2009)
COMPRENDO: Focus and Approach
Authors: Ulrike Schulte-Oehlmann, Triantafyllos Albanis, Axel Allera, Jean Bachmann, Pia Berntsson, Nicola Beresford, Daniela Candia Carnevali, Francesca Ciceri, Thierry Dagnac, Jerzy Falandysz, Silvana Galassi, David Hala, Gemma Janer, Roger Jeannot, Susan Jobling, Isabella King, Dietrich Klingmüller, Werner Kloas, Kresten Ole Kusk, Ramon Levada, Susan Lo, Ilka Lutz, Jörg Oehlmann, Stina Oredsson, Cinta Porte, Marian Rand-Weaver, Vasilis Sakkas, Michela Sugni, Charles Tyler, Ronny van Aerle, Christoph van Ballegoy, Leah Wollenberger
Journal: Environmental Health Perspectives (2006)

Tens of thousands of man-made chemicals are in regular use and discharged into the environment. Many of them are known to interfere with the hormonal systems in humans and wildlife. Given the complexity of endocrine systems, there are many ways in which endocrine-disrupting chemicals (EDCs) can affect the body’s signaling system, and this makes unraveling the mechanisms of action of these chemicals difficult. A major concern is that some of these EDCs appear to be biologically active at extremely low concentrations. There is growing evidence to indicate that the guiding principle of traditional toxicology that “the dose makes the poison” may not always be the case because some EDCs do not induce the classical dose–response relationships. The European Union project COMPRENDO (Comparative Research on Endocrine Disrupters—Phylogenetic Approach and Common Principles focussing on Androgenic/Antiandrogenic Compounds) therefore aims to develop an understanding of potential health problems posed by androgenic and antiandrogenic compounds (AACs) to wildlife and humans by focusing on the commonalities and differences in responses to AACs across the animal kingdom (from invertebrates to vertebrates).
Blockade of Complement Inhibits Obliterative Bronchiolitis in Rat Tracheal Allografts
Authors: ERKKI A. KALLIO, KARL B. LEMSTRÖM, PEKKA J. HÄYRY, UNA S. RYAN, PETRI K. KOSKINEN
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

The role of complement activation in the development of obliterative bronchiolitis, a manifestation of chronic lung allograft rejection, was investigated in the heterotopic rat tracheal allograft model. An increase in intragraft complement components C3 and C5b-9 (membrane attack complex) as well as IgM and IgG deposits were demonstrated during the progressive loss of respiratory epithelium and airway occlusion in nontreated allografts compared with syngeneic grafts. A 7-d treatment with recombinant human soluble complement receptor type 1 (sCR1; 20 mg/kg/d, intraperitoneal), an inhibitor of both the classic and alternative complement pathways, significantly decreased epithelial necrosis and intragraft neutrophil infiltration, and reduced obliterative changes by 40%. Immunohistochemical analysis of the grafts showed that sCR1 treatment significantly decreased early C5b-9 and IgG deposits, neutrophil chemoattractant IL-8 immunoreactivity, and ICAM-1 expression. Treatment with sCR1 was associated with increased staining for Th2 cytokines, in particular IL-10, with concomitant downregulation of IL-2 and TNF- α immunoreactivity. In contrast, sCR1 treatment did not affect the number of graft-infiltrating CD4+ and CD8+ T cells, CD45+ B cells, ED1+ and ED3+ macrophages, or immune activation with expression of IL-2R α or MHC class II. In conclusion, this is the first study to demonstrate that blockade of complement activation attenuates the development of OB and suggests that in addition to T cell-driven responses, humoral and antigen-independent immune responses also operate in the disease process. A blockade of complement activation renders the chemokine milieu unattractive to neutrophils and also modulates the alloimmune response toward Th2 cytokines, which may have an antiproliferative role in fibroproliferative disorders.
Heterozygous deficiency of hypoxia-inducible factor–2α protects mice against pulmonary hypertension and right ventricular dysfunction during prolonged hypoxia
Authors: Koen Brusselmans, Veerle Compernolle, Marc Tjwa, Michael S. Wiesener, Patrick H. Maxwell, Désiré Collen, Peter Carmeliet
Journal: Journal of Clinical Investigation (2003)

Chronic hypoxia induces pulmonary vascular remodeling, leading to pulmonary hypertension, right ventricular hypertrophy, and heart failure. Heterozygous deficiency of hypoxia-inducible factor–1α (HIF-1α), which mediates the cellular response to hypoxia by increasing expression of genes involved in erythropoiesis and angiogenesis, has been previously shown to delay hypoxia-induced pulmonary hypertension. HIF-2α is a homologue of HIF-1α and is abundantly expressed in the lung, but its role in pulmonary hypertension remains unknown. Therefore, we analyzed the pulmonary response of WT and viable heterozygous HIF-2α–deficient (Hif2α+/–) mice after exposure to 10% O2 for 4 weeks. In contrast to WT mice, Hif2α+/– mice were fully protected against pulmonary hypertension and right ventricular hypertrophy, unveiling a critical role of HIF-2α in hypoxia-induced pulmonary vascular remodeling. Pulmonary expression levels of endothelin-1 and plasma catecholamine levels were increased threefold and 12-fold respectively in WT but not in Hif2α+/– mice after hypoxia, suggesting that HIF-2α–mediated upregulation of these vasoconstrictors contributes to the development of hypoxic pulmonary vascular remodeling.
Emergency Department Treated Asthmatics have Elevated Levels of Plasma Complement Split Products (CSP) and Peripheral Blood CSP Receptor (CSPr) Levels Greater than those from Outpatient Asthmatics
Authors: H SOLOMON, D DURE, S CHICE, I KALAMPOKIS, M NOWAKOWSKI, H DURKIN, R JOKS
Journal: Journal of Allergy and Clinical Immunology (2008)
Polymyalgia rheumatica is characterised by pro-inflammatory, late stage CD8+ T cells
Authors: K S M van der Geest, W H Abdulahad, M G Huitema, B J Kroesen, A Rutgers, A M H Boots, E Brouwer
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Backgroundand objectives</h3> Polymyalgia rheumatica (PMR) is a frequent, inflammatory rheumatic disease affecting older people. Previous studies suggest that T cell mediated immune responses contribute to PMR. However, little is known about CD4+ and CD8+ T cell subsets and their function in PMR. Furthermore, it remains to be elucidated whether immune ageing contributes to the development of this age-related disease. The authors hypothesised that senescent T cells can functionally contribute to PMR pathogenesis. Therefore, the authors studied frequencies of circulating T cell subsets in defined stages of differentiation and assessed characteristics of senescent (CD28 null) T cells in PMR patients. <h3>Materials and methods</h3> Peripheral blood was obtained from eight newly-diagnosed, untreated PMR patients. Thirty-nine healthy age- matched older controls were recruited from the Groningen Longevity Cohort. Flow cytometric analysis of CD45RO, CCR7 and CD28 expression was used to enumerate CD4+ and CD8+ T cell differentiation subsets and senescent (CD28null) T cells. Furthermore, naïve and memory regulatory T cells were identified based on CD25 and CD45RA expression. In addition, full blood of all PMR patients and eleven older controls was stimulated with PMA/calcium-ionophore in the presence of brefeldin A during 4 h. This was followed by intracellular staining for IFNγ, TNF, IL-4 and IL-17. <h3>Results</h3> Compared to healthy controls, PMR patients had decreased percentages of circulating terminally differentiated (CD45RO-CCR7-) CD4+ T cells. However, the authors did not observe altered percentages of Th1, Th2, or Th17 cells in PMR patients. In addition, percentages of naïve and memory regulatory T cells were normal in PMR patients. In CD8+ T cells of PMR patients, percentages of naïve (CD45RO-CCR7+) cells were decreased. Interestingly, percentages of CD28null cells were increased within the effector memory (CD45RO+CCR7+) and terminally differentiated CD8+ T cell populations of PMR patients. Moreover, a significantly increased potential to produce IFN-gamma and a strong trend towards more TNF production were observed in CD8+T cells of PMR patients. <h3>Conclusions</h3> Our data showed premature immune ageing (loss of CD28) of effector memory and terminally differentiated CD8+T cells in PMR-patients. This was associated with an enhanced pro-inflammatory potential of CD8+ T cells. In contrast, the authors observed no clear alterations of Th-subsets and regulatory T cells in PMR patients. Altogether, these findings imply a role for late stage CD8+ T cells in PMR pathogenesis.
Automobile Accidents in Patients with Sleep Apnea Syndrome
Authors: FERRAN BARBÉ, JORDI PERICÁS, ARACELI MUÑOZ, LARRY FINDLEY, JOSEP MARÍA ANTÓ, ALVAR G.N. AGUSTÍ, MARIA de LLUC JOAN
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

To investigate the association between sleep apnea syndrome (SAS) and automobile accidents, and to evaluate potential underlying mechanisms, we prospectively recruited 60 consecutive patients with SAS (apnea-hypopnea index, 58 +/- 3 h-1) and 60 healthy control subjects, matched for sex and age. The number of automobile accidents during the past 3 yr was obtained from participants and insurance companies. We quantified the degree of daytime sleepiness (Epworth scale), anxiety and depression (Beck tests), and we assessed the level of vigilance (PVT 192) and driving performance (Steer-Clear). Patients had more accidents than control subjects (OR: 2.3; 95% CI: 0.97 to 5.33) and were more likely to have had more than one accident (OR: 5.2; 95% CI: 1.07 to 25.29, p < 0.05). These differences persisted after stratification for km/yr, age, and alcohol consumption. Patients were more somnolent, anxious, and depressed than control subjects (p < 0.01), and they had a lower level of vigilance and poorer driving performance (p < 0.01). Yet, we did not find any correlation between the degree of daytime sleepiness, anxiety, depression, the number of respiratory events, nocturnal hypoxemia, level of vigilance, or driving simulator performance and the risk of automobile accidents among SAS patients. In conclusion, patients with SAS have an increased risk of automobile accidents. None of the clinical or physiological markers commonly used to define disease severity appear able to discriminate those patients at higher risk of having an automobile accident.
Th17: An Effector CD4 T Cell Lineage with Regulatory T Cell Ties
Authors: Casey T. Weaver, Laurie E. Harrington, Paul R. Mangan, Maya Gavrieli, Kenneth M. Murphy
Journal: Immunity (2006)

The naive CD4 T cell is a multipotential precursor with defined antigen recognition specificity but substantial plasticity for development down distinct effector or regulatory lineages, contingent upon signals from cells of the innate immune system. The range of identified effector CD4 T cell lineages has recently expanded with description of an IL-17-producing subset, called Th17, which develops via cytokine signals distinct from, and antagonized by, products of the Th1 and Th2 lineages. Remarkably, Th17 development depends on the pleiotropic cytokine TGF-β, which is also linked to regulatory T cell development and function, providing a unique mechanism for matching CD4 T cell effector and regulatory lineage specification. Here, we review Th17 lineage development, emphasizing similarities and differences with established effector and regulatory T cell developmental programs that have important implications for immune regulation, immune pathogenesis, and host defense.
Salmonella arteritis: an unusual cause of low back pain
Authors: D Pyne
Journal: Annals of the Rheumatic Diseases (2001)

Salmonella arteritis is a rare condition, first reported in 1948. 1 Salmonella typhimurium is responsible for most cases and here we report a case of S typhimurium septicaemia with subsequent arteritis and aneurysm formation. Case reportA 70 year old Afro-Caribbean man, previously fit and well, was admitted to hospital with a two month history of malaise, anorexia, weight loss of 6.5 kg, constipation, low lumbar back pain, and frequency of micturition.The back pain was a dull, constant ache, present day and night, without radiation.He was not receiving regular drug treatment.He smoked 20 cigarettes a day.On initial examination he was pyrexial at 38°C, pulse rate 100 beats/min, normotensive, and dehydrated.Cardiovascular and respiratory examination were normal.There was suprapubic tenderness but no abdominal masses or organomegaly.The lower lumbar spine was tender and range of movement was limited in all directions as a result of pain.Investigations showed haemoglobin 102 g/l, mean cell volume 74 fl, white cell count 12.1×10 9 /l (neutrophils 84%), erythrocyte sedimentation rate 42 mm/1st h, C reactive protein (CRP) 326 mg/l, urine dipstix trace leucocytes and no proteinuria, and blood cultures showed no growth.A lumbar spine x ray examination showed degenerative changes and erosion of the end plate between L4 and L5 vertebrae.A bone scan was normal.Culture from the urine grew S typhimurium, and ciprofloxacin 500 mg twice a day was started orally.Over the next week the patient improved, and ciprofloxacin was discontinued after a course of 10 days.Three days later the haemoglobin fell suddenly to 78 g/l.There was no overt bleeding or cardiovascular compromise.The abdomen was non-tender with no masses, and a rectal examination was normal.The source of the bleed was unclear.Two units of blood were transfused.Oesophagogastro-duodenoscopy showed only mild gastritis, unlikely to explain the sudden anaemia, and a colonoscopy was normal.The following week the patient became pyrexial again (38°C).Repeat cultures of the urine were negative but blood cultures grew S typhimurium.
Intratracheal Endotoxin Causes Systemic Inflammation in Ventilated Preterm Lambs
Authors: BORIS W. KRAMER, MACHIKO IKEGAMI, ALAN H. JOBE
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

Intratracheal endotoxin causes acute inflammation in the adult lung, and injurious styles of mechanical ventilation can result in systemic inflammation derived from the lungs. We asked how ventilated premature and near-term lungs responded to intratracheal endotoxin and if systemic inflammation occurred. Lambs delivered at 130 d gestational age (GA) were treated with surfactant or surfactant plus endotoxin (0.1 mg/kg or 10 mg/kg) (Escherichia coli, serotype O55:B5) and were ventilated for 6 h. Both endotoxin doses resulted in impaired gas exchange and systemic inflammation in the preterm lambs. Lambs at 141 d GA (term 146 d) were given either 10 mg/kg intratracheal endotoxin, 10 mg/kg endotoxin plus high tidal volume ventilation for the first 30 min of life, or 5 μ g/kg endotoxin given intravenously. Endotoxin alone (10 mg/kg) caused lung inflammation but no systemic effects after 6 h of ventilation. Lambs given 10 mg/kg endotoxin plus high tidal volume ventilation or 5 μ g/kg endotoxin intravenously had decreased gas exchange and systemic inflammation. Endotoxin was detected in the plasma of lambs at 130 d GA but not at 141 d GA. Inflammation in the lungs was more severe in preterm animals. Mechanical ventilation of the endotoxin-exposed preterm lung resulted in systemic effects at a low endotoxin dose and without high tidal volume ventilation.
T-Cell Response in B-Cell Lymphomas: Favorable or Unfavorable?
Authors: Joost J. Oudejans, Jettie J.F. Muris, Saskia A.G.M. Cillessen, Chris J.L.M. Meijer
Journal: Clinical Cancer Research (2008)

To the Editors: In a recent issue of Clinical Cancer Research, Chang and colleagues reported that in patients with diffuse large B-cell lymphoma, the presence of an intense cytotoxic T-cell infiltrate was associated with a favorable clinical outcome (1). These observations are in contrast with our previous reports, and by other reports, which show that the presence of many activated cytotoxic T-cells in primary nodal diffuse large B-cell lymphomas is in fact a strong International Prognostic Index–independent indicator for an unfavorable clinical outcome (2, 3). We recently confirmed this association by microarray expression analysis, which also identified a group of patients with primary nodal diffuse large B-cell lymphoma with a very poor clinical outcome that was characterized by high expression levels of cytotoxic T-cell effector molecules including granzyme B and perforin (4). The possible causes for these conflicting data are not clear but could result from differences in the methods used for quantification of the T cells or by selection of analyzed areas of tumor specimens.It is unclear why Chang et al. did not cite these previous articles. Chang et al. conclude that enhancing this putative antitumor T-cell immune response is a possible target for diffuse large B-cell lymphoma immunotherapy (1). Based on our data, and the data reported by Hasselblom et al. (3), we think that this is unlikely. Apparently, in cases with many activated CTLs, these T cells are also incapable of effectively killing the lymphoma cells. Hasselblom et al. showed that this is probably not caused by the presence of Foxp3 immunosuppressive T cells (3). We have previously suggested that lymphoma cells might escape from CTL-induced apoptosis not only by interfering with proper antigen presentation but also by disruption of the intracellular apoptosis pathway (2). This latter mechanism could also explain the poor response to the apoptosis-inducing chemotherapy. Thus, from this point of view, not enhancing the antilymphoma T-cell response, but rather, restoring apoptosis sensitivity will be a promising new therapy for patients with chemotherapy-refractory diffuse large B-cell lymphoma. Recently, we have shown that this is indeed a highly promising approach (5).No potential conflicts of interest were disclosed.