tbuckley/cabot-search huggingface dataset:
Lung clearance index in adult cystic fibrosis patients: the role of convection-dependent lung units
Authors: Sylvia Verbanck, Manuel Paiva, Erika Paeps, Daniel Schuermans, Anne Malfroot, Walter Vincken, Eef Vanderhelst
Journal: European Respiratory Journal (2012)

We investigated the extent of convective ventilation heterogeneity contributing to the observed lung clearance index values in adult cystic fibrosis patients, as the result of two simulated scenarios, either 1) a fixed part of the lungs becoming increasingly less compliant, or 2) an increasingly greater part of the lung being less compliant. In 25 cystic fibrosis patients and 25 matched controls, we computed the lung clearance index and also quantified curvilinearity of the washout concentration curve, where curvilinearity is equal to 0 (linear in semilog plot) reflects homogeneous ventilation and curvilinearity equal to 1 corresponds to the presence of an infinitesimally slowly emptying lung unit. In the cystic fibrosis group (forced expiratory volume in 1 s 27-100% predicted), lung clearance index and curvilinearity average±sd values were 10.3±2.3 and 0.57±0.13, respectively, and were significantly different from control values (6.2±0.4 and 0.18±0.07; both p<0.001); lung clearance index and curvilinearity were also correlated (R = 0.67; p<0.001). The average curvilinearity value in the cystic fibrosis group was found to be compatible with a cumulative volume of underventilated lung of 40-50%, depending on the simulation scenario considered. The degree of washout curvilinearity observed here indicates that a major determinant of the abnormal lung clearance index values observed in adult cystic fibrosis patients is ventilation heterogeneity generated between convection-dependent lung units, while the remainder of lung clearance index abnormality with respect to normal controls potentially represents the small airways within these lung zones.
NITROGEN, POTASSIUM, SODIUM, AND CHLORINE METABOLISM IN RICKETS, WITH SPECIAL REFERENCE TO BILIARY FISTULA RICKETS IN PUPPIES
Authors: Walter Heymann
Journal: The Journal of Experimental Medicine (1936)

1. Rickets developed in three puppies deprived of vitamin D and sunlight since birth, in which, at the age of 6 to 7 weeks gall bladder fistula was established. The results of studies of their bones and of the calcium and phosphate metabolism have previously been published (2). Studies on the nitrogen, potassium, sodium, and chlorine metabolism, here presented, reveal that the metabolism was greatly interfered with as compared with that in three controls without gall bladder fistula rickets. This interference, together with an inhibited gain in weight, demonstrates that the pathogenesis of biliary, fistula rickets in puppies has to be considered distinctly different from infantile rickets as well as from rickets produced in rats. 2. The nitrogen, potassium, sodium, and chlorine metabolism was also studied in three rachitic and four healthy infants, and in eleven rachitic and six control rats. The balance of these substances, as well as their distribution in stool and urine, proved to be the same whether or not rickets was present. 3. The pathogenesis of biliary fistula rickets is discussed on the basis of these studies. The assumption has been made that deficiency in other vitamins than vitamin D might have a bearing upon the development of this disease. Further study with a view to possible elimination of these unspecific factors might lead to the experimental production by gall bladder fistula of a purely rachitic state. 4. The normal balance and distribution of nitrogen, potassium, sodium, and chlorine in the stool and urine of rachitic infants and rats are considered further evidence of the hypothetical nature of the so called absorption theory in infantile rickets.
Lung Inflammation Induced by Concentrated Ambient Air Particles Is Related to Particle Composition
Authors: Paulo H. N. Saldiva, Robert W. Clarke, Brent A. Coull, Rebecca C. Stearns, Joy Lawrence, G. G. Krishna Murthy, Edgar Diaz, Petros Koutrakis, Helen Suh, Akira Tsuda, John J. Godleski
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

The objectives of this study were (1) to determine whether short-term exposures to concentrated air particles (CAPs) cause pulmonary inflammation in normal rats and rats with chronic bronchitis (CB); (2) to identify the site within the lung parenchyma where CAPs-induced inflammation occurs; and (3) to characterize the component(s) of CAPs that is significantly associated with the development of the inflammatory reaction. Four groups of animals were studied: (1) air treated, filtered air exposed (air-sham); (2) sulfur dioxide treated (CB), filtered air exposed (CB-sham); (3) air treated, CAPs exposed (air-CAPs); and (4) sulfur dioxide treated, CAPs exposed (CB-CAPs). CB and normal rats were exposed by inhalation either to filtered air or CAPs during 3 consecutive days (5 hours/day). Pulmonary inflammation was assessed by bronchoalveolar lavage (BAL) and by measuring the numerical density of neutrophils (Nn) in the alveolar walls at the bronchoalveolar junction and in more peripheral alveoli. CAPs (as a binary exposure term) and CAPs mass (in regression correlations) induced a significant increase in BAL neutrophils and in normal and CB animals. Nn in the lung tissue significantly increased with CAPs in normal animals only. Greater Nn was observed in the central compared with peripheral regions of the lung. A significant dose-dependent association was found between many CAPs components and BAL neutrophils or lymphocytes, but only vanadium and bromine concentrations had significant associations with both BAL neutrophils and Nn in CAPs-exposed groups analyzed together. Results demonstrate that short-term exposures to CAPs from Boston induce a significant inflammatory reaction in rat lungs, with this reaction influenced by particle composition.
Multiple intracellular pathways for regulation of chloride secretion in cultured pig tracheal submucosal gland cells
Authors: AL Zhang, GM Roomans
Journal: European Respiratory Journal (1999)

Tracheal submucosal glands are of great relative importance in the secretion of chloride and water to the airway lumen. This study aimed to examine whether the cystic fibrosis transmembrane conductance regulator (CFTR) is involved in cyclic adenosine monophosphate (cAMP) or Ca2+-activated Cl- secretion. Regulation of Cl- secretion in cell cultures derived from pig tracheal submucosal gland acini was investigated by X-ray microanalysis. With or without preincubation with CFTR antisense oligodeoxynucleotide (5 microM). A significant decrease in cellular Cl and K concentration was induced by 5 mM 8-bromo-adenosine 3': 5'-cyclic monophosphate (8-bromo-cAMP), 3 microM calcium ionophore ionomycin, 200 microM 5'-uridine triphosphate (UTP) and 200 microM 5'-adenosine triphosphate (ATP), respectively. The decrease in cellular Cl content was significantly inhibited by the Cl- channel blocker 5-nitro-2-(3-phenylpropyl-amino)-benzoic acid (NPPB; 50 microm). Preincubation of the cells with CFTR antisense oligodeoxynucleotide significantly inhibited the 8-bromo-cAMP-induced decrease in Cl, whereas CFTR sense oligodeoxynucleotide had no effect. The effects of ionomycin, ATP or UTP were not blocked by either CFTR antisense oligodeoxynucleotide or CFTR sense oligodeoxynueleotide. To measure the cytosolic free calcium concentration ([Ca2+]i) the cells grown on glass coverslips were loaded with fura-2 tetraoxymethylester (fura-2 AM; 5 microM). The [Ca2+]i was measured as the fluorescence ratio of emission (340/380 nm). Ionomycin (3 microM) caused a rapid increase in [Ca2+]i followed by a sustained plateau, but 8-bromo-cAMP had a more complex effect on [Ca2+]i. Exposure to ATP or UTP caused a rapid increase in [Ca2+]i followed by a decrease. In conclusion, cystic adenosine monophosphate and ionomycin induced Cl- secretion through different intracellular pathways. Adenosine triphosphate and uridine triphosphate also induced Cl- secretion probably with Ca as an intracellular messenger. The cystic fibrosis transmembrane conductance regulator is not involved in Cl- secretion activated by extracellular adenosine triphosphate and uridine triphosphate.
Toll-like receptor 2 controls expansion and function of regulatory T cells
Authors: R. P.M. Sutmuller
Journal: Journal of Clinical Investigation (2006)

Tregs play a central role in the suppression of immune reactions and prevention of autoimmune responses harmful to the host. During acute infection, however, Tregs might hinder effector T cell activity directed toward the elimination of the pathogenic challenge. Pathogen recognition receptors from the TLR family expressed by innate immune cells are crucial for the generation of effective immunity. We have recently shown the CD4CD25 Treg subset in TLR2 mice to be significantly reduced in number compared with WT littermate control mice, indicating a link between Tregs and TLR2. Here, we report that the TLR2 ligand Pam3Cys, but not LPS (TLR4) or CpG (TLR9), directly acts on purified Tregs in a MyD88-dependent fashion. Moreover, when combined with TCR stimulation, TLR2 triggering augmented Treg proliferation in vitro and in vivo and resulted in a temporal loss of the suppressive Treg phenotype in vitro by directly affecting Tregs. Importantly, WT Tregs adoptively transferred into TLR2 mice were neutralized by systemic administration of TLR2 ligand during the acute phase of a Candida albicans infection, resulting in a 100-fold reduced C. albicans outgrowth. This demonstrates that in vivo TLR2 also controls the function of Tregs and establishes a direct link between TLRs and the control of immune responses through Tregs.
Gastric tonometry after subarachnoid hemorrhage
Authors: T. Koivisto, M. Vapalahti, I. Parviainen, J. Takala
Journal: Intensive Care Medicine (2001)

To evaluate splanchnic tissue perfusion, assessed by gastric tonometry, in patients with subarachnoid hemorrhage (SAH) and to study the effect of treatment, either surgical or endovascular, and the severity of initial SAH on splanchnic tissue perfusion.Prospective observational substudy, part of a randomised controlled trial of early treatment of ruptured intracranial aneurysms.Intensive care unit (ICU) of a university hospital.A consecutive sample of 26 patients [13 surgical (7/6 Hunt & Hess Grade I-II/H & H Gr IV-V) and 13 endovascular (3/10 H & H Gr I-II/H & H Gr IV-V)] out of 56 SAH patients randomly assigned to either endovascular or surgical treatment during the substudy period between 1 May 1995 and 31 August 1996. All patients were treated within 72 h after SAH.After treatment of a ruptured aneurysm, hemodynamics and gastric intramucosal pCO2 were measured during the first 4 h and between 6 h and 12 h after aneurysm treatment. In the whole sample, neither the gastric intramucosal-arterial pCO2 difference (pCO2 gap) (1.5+/-1.9 kPa and 1.7+/-1.2 kPa, NS) nor gastric intramucosal pH (7.28+/-0.12 and 7.29+/-0.08, NS) changed during the study. There were no differences in pCO2 gap or gastric intramucosal pH between treatment groups or Hunt & Hess grade groups during the study period.Splanchnic tissue perfusion may be insufficient even though there is no systemic hemodynamic disturbance in patients after SAH. Neither the therapeutic treatment nor pre-treatment Hunt & Hess grade is associated with a specific pattern of pCO2 gap.
Human macromolecular insoluble cold globulin (MICG). I. T-cell origin of T-MICG and null cell origin of N-MICG.
Authors: S P Hauptman, E Kansu, M Serno, S Godfrey
Journal: The Journal of Experimental Medicine (1979)

Although surface immunoglobulin characterizes B cells in man, there are few surface markers that distinguish T cells. We have described a new protein synthesized in human T cells, termed T-MICG. This protein is a macromolecule of 225,000 daltons, is insoluble in the cold, and migrates as a beta-globulin on electrophoresis. Separation of human peripheral blood lymphocytes into T and B-cell populations by rosette sedimentation and anti-human-Fab columns clearly demonstrated the T-cell origin of the 225,000 dalton component. Furthermore, null cells were shown to synthesize a protein of 185,000 daltons, termed N-MICG, with physical properties similar to T-MICG, T-MICG and N-MICG were shown to be antigenically dissimilar, employing antiserum to each of these proteins. The present studies demonstrate two novel cell surface markers, T-MICG and N-MICG, which characterize T cells and null cells, respectively.
Influence of biological agents on cardiovascular disease in rheumatoid arthritis
Authors: Johan Askling, Will Dixon
Journal: Annals of the Rheumatic Diseases (2011)

A wealth of studies has demonstrated that patients with rheumatoid arthritis (RA) are at increased risk of cardiovascular morbidity and mortality, and that this increase is manifest early in the course of RA.1 2 Another wealth of studies has shown the increasing efficacy of recent therapies, or therapeutic strategies, in reducing disease activity in RA. As the inflammatory burden in RA may partly explain the increased cardiovascular risk, can effective therapy reduce the cardiovascular risk in RA? Unfortunately, and as indicated in the interesting report by Greenberg et al 3 in this issue of the journal ( pp 576–582 ), ‘Despite the published evidence of a heightened cardiovascular risk for patients with RA, few studies have investigated therapeutic strategies to reduce this risk.’ Since cardiovascular disease makes up a considerable part of the excess burden of disease and premature mortality in RA, the clinical importance of this issue cannot be underestimated. We must therefore carefully appraise the methods and results of such studies and consider future directions.

With increasing emphasis on long-term safety and disease outcomes beyond short-term EULAR DAS28 response or ACR70 we need, and are likely to see more of, studies from disease registers such as that by Greenberg et al from the CORRONA registry (reviewed in Curtis et al 4 and Zink et al ).5 However, as multiple registers address the same scientific question, we need to understand why results from different studies on the same topic may come out quite differently. Cardiovascular events following antitumour necrosis factor (TNF) therapy is an excellent example: the CORRONA study in this issue reports a greater than twofold reduction in cardiovascular risk for anti-TNF-treated patients compared with non-biological non-methotrexate disease-modifying antirheumatic drug (DMARD)-treated patients a finding contrasting with other null studies of anti-TNF.6,–,9 They also …
White Blood Cell Monitoring During Long-Term Clozapine Treatment
Authors: Dan Cohen, Marcel Monden
Journal: American Journal of Psychiatry (2013)

Late-onset agranulocytosis is rare during treatment with clozapine, especially in monotherapy. The authors describe a case of agranulocytosis that emerged after 19 years of continuous clozapine monotherapy. The discovery of the agranulocytosis was due to the lifelong white blood cell counts that are now required for clozapine treatment. Despite the fact that this requirement probably saved the life of this patient, this monitoring is not evidence-based because the incidence of agranulocytosis does not exceed that of conventional antipsychotic drugs, for which no such requirement exists. For mentally competent and adequately informed patients, the Netherlands Clozapine Collaboration Group now permits quarterly monitoring after the first 6 months of clozapine treatment.
Angiotensin Converting Enzyme Insertion/Deletion Polymorphism Is Associated with Susceptibility and Outcome in Acute Respiratory Distress Syndrome
Authors: Richard P. Marshall, Suzanne Webb, Geoffrey J. Bellingan, Hugh E. Montgomery, Babar Chaudhari, Robin J. McAnulty, Steve E. Humphries, Mike R. Hill, Geoffrey J. Laurent
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

Acute respiratory distress syndrome (ARDS) is an often fatal condition for which a genetic predisposition is postulated, although no specific genes have been identified to date. Angiotensin converting enzyme (ACE) has a potential role in the pathogenesis of ARDS via effects on pulmonary vascular tone/permeability, epithelial cell survival, and fibroblast activation. Forty-seven percent of the variance in plasma ACE activity is accounted for by the ACE insertion/deletion (I/D) polymorphism, the D allele being associated with higher activity. We therefore hypothesized that the presence of the D allele would be associated with the development of ARDS. Ninety-six white patients fulfilling American/European Consensus Committee criteria for ARDS were genotyped for the ACE polymorphism together with individuals from three comparison groups: 88 white patients with non-ARDS respiratory failure ventilated in the intensive care unit (ICU), 174 ICU patients undergoing coronary artery bypass grafting, and 1,906 individuals from a general population group. DD genotype frequency was increased in the patients with ARDS compared with the ICU (p = 0.00008), coronary artery bypass grafting (p = 0.0009), and general population group (p = 0.00004) control groups and was significantly associated with mortality in the ARDS group (p < 0.02). These data suggest a potential role for renin-angiotensin systems in the pathogenesis of ARDS and for the first time implicate genetic factors in the development and progression of this syndrome.
Mineralogical analysis of the respiratory tract in aluminium oxide-exposed workers
Authors: C Voisin, F Fisekci, B Buclez, A Didier, B Couste, F Bastien, P Brochard, JC Pairon
Journal: European Respiratory Journal (1996)

A retrospective study was conducted in order to characterize the retention of fibrous and nonfibrous mineral particles in the respiratory tract in subjects with previous occupational exposure in the aluminium industry. Bronchoalveolar lavage (BAL) fluid (three samples) or lung parenchyma (two samples) were studied using analytical transmission electron microscopy in five patients. A high concentration of aluminium fibres (&gt; 10(7) fibres.g-1 dry lung) was identified in two lung tissue samples, and aluminium fibres were also identified in BAL fluid in three patients. All fibres were short (mean length: 1-2 microns), with no fibre longer than 5 microns. Some biopersistence of these fibres in the respiratory tract is suggested from these observations, since fibres were identified in biological samples collected more than 4 yrs after cessation of exposure in four out of five patients. Occupational physicians should be aware of possible exposure to short, thin aluminium fibres during primary aluminium production. Further studies are needed to assess the potential health effects of these fibres. Industrial hygiene measurements should also be performed to document the potential sources of exposure to aluminium fibres in this industry.
<b> <i>TEL</i> </b> Deletion Analysis Supports a Novel View of Relapse in Childhood Acute Lymphoblastic Leukemia
Authors: Jan Zuna, Anthony M. Ford, Martina Peham, Naina Patel, Vaskar Saha, Cornelia Eckert, Joachim Köchling, Renate Panzer-Grümayer, Jan Trka, Mel Greaves
Journal: Clinical Cancer Research (2004)

TEL (ETV6)-AML1 (RUNX1) chimeric gene fusions are frequent genetic abnormalities in childhood acute lymphoblastic leukemia (ALL). They often arise prenatally as early events or initiating events and are complemented by secondary postnatal genetic events of which deletion of the non-rearranged, second TEL allele is the most common. This consistent sequence of molecular pathogenesis facilitates an analysis of the clonal origins of relapse in this leukemia, which has some unusual clinical features.We compared the boundaries, by microsatellite mapping, of TEL deletions at relapse versus diagnosis in 15 informative patients. Moreover, we compared the relatedness of diagnostic and relapse clones using immunoglobulin and T-cell receptor genes rearrangements and clonotypic TEL-AML1 genomic fusion.Five patients retained the apparent same size TEL deletion, seven had larger deletions, and three had smaller deletions at relapse. In all of the cases evaluated, the clonal relatedness of diagnostic and relapse cells was confirmed by the retention of clonotypic TEL-AML1 genomic sequence and/or at least one identical immunoreceptor gene rearrangement.These data provide further evidence that TEL deletions are secondary to TEL-AML1 fusions in ALL. They are compatible with the novel idea that in at least some cases of childhood ALL, remission occurs with persistence of a preleukemic "fetal" clone, and subsequent relapse reflects the emergence of a new subclone from this reservoir after an independent "second hit," i.e., independent TEL deletion. To our knowledge, the study is the most extensive and comprehensive analysis of the relationship between diagnostic and relapse clones in childhood ALL presented thus far.
The Attorney As the Newest Member of the Cancer Treatment Team
Authors: Stewart B. Fleishman, Randye Retkin, Julie Brandfield, Victoria Braun
Journal: Journal of Clinical Oncology (2006)

In a recent survey of cancer patients conducted by the Lance Armstrong Foundation (Austin, TX), nearly half of the individuals surveyed said that nonmedical issues relating to their cancer were unmet by their oncologists, including 35% who said nonmedical issues were wholly unaddressed and another 14% who said they believed their oncologists wanted to assist with nonmedical issues but did not have enough information or experience to do so. More is being done to integrate basic symptom management into routine cancer treatment, including early intervention for pain, fatigue, adverse effects of treatment, and adjustment to life in anticipation of cancer survivorship. Until now, little has been done to integrate legal advocacy services into the cancer treatment matrix, especially for patients who are medically underserved and from hard to reach communities. Legal problems for patients with cancer are a significant nonmedical need that must be addressed to maintain quality of life during and after cancer treatment and to promote continued access to care. As the number of cancer survivors steadily increases, many patients still face extended survivorship or progressive illness, often creating complicated end-of-life decisions for the patients and their families and treatment staff. These decisions are often made without the involvement or advice of legal counsel. Traditionally, an historical and outdated tension between physicians and attorneys over contentious malpractice litigation discouraged their collaboration. With the advent of multidisciplinary care, the input of interested attorneys benefits patients and their families, oncology professionals, and the offices and cancer centers where the professionals practice. Other barriers to proactive attorney involvement include the prioritization of the tasks of treatment over personal issues until they impede care, a lack of immediate and easy access to legal counsel, and a lack of knowledge base within the cancer treatment team, delaying intervention until it is too late and the patient is in crisis.
A 28-year-old snowboarder presents with chronic ankle pain
Authors: Lawrence B Josey, Christian Kirkpatrick, Gordon Andrews, Bruce B Forster
Journal: British Journal of Sports Medicine (2013)

An active, 28-year-old female snowboarder presented to the sports medicine clinic with a history of chronic right ankle pain. The pain was localised to the medial ankle, dull in character and exacerbated with prolonged weight bearing. Examination revealed generalised pain deep …