tbuckley/cabot-search huggingface dataset:
Corticosteroids Induce Expression of Aquaporin-1 and Increase Transcellular Water Transport in Rat Peritoneum
Authors: Maria S. Stoenoiu, Jie Ni, Charlotte Verkaeren, Huguette Debaix, Jean-Christophe Jonas, Norbert Lameire, Jean-Marc Verbavatz, Olivier Devuyst
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. The water channel aquaporin-1 (AQP1) is the molecular counterpart of the ultrasmall pore responsible for transcellular water permeability during peritoneal dialysis (PD). This water permeability accounts for up to 50% of ultrafiltration (UF) during a hypertonic dwell, and its loss can be a major clinical problem for PD patients. By analogy with the lung, the hypothesis was tested that corticosteroids may increase AQP1 expression in the peritoneal membrane (PM) and improve water permeability and UF in rats. First, the expression and distribution of the glucocorticoid receptor (GR) in the PM and capillary endothelium was documented. Time-course and dose-response analyses showed that a daily IM injection of dexamethasone (1 or 4 mg/kg) for 5 d induced an approximately twofold increase in the expression of AQP1 at the mRNA and protein levels. The GR antagonist RU-486 completely inhibited the dexamethasone effect. The functional counterpart of the increased AQP1 expression was a significant increase in sodium sieving and net UF across the PM, contrasting with a lack of effect on the osmotic gradient and permeability for small solutes. The latter observation reflected the lack of effect of corticosteroids on nitric oxide synthase (NOS) activity and endothelial NOS isoform expression in the PM. In conclusion, corticosteroids induce AQP1 expression in the capillary endothelium of the PM, which is reflected by increased transcellular water permeability and UF. These data emphasize the critical role of AQP1 during PD and suggest that pharmacologic regulation of AQP1 may provide a target for manipulating water permeability across the PM. E-mail: [email protected]
Evidence-based medicines for children: ethical aspects
Authors: A. Gammelgaard, H. Bisgaard
Journal: European Respiratory Journal (2007)

To the Editors: 

In an editorial in the December issue of the European Respiratory Journal , Bush 1 describes and welcomes newly proposed legislation from the European Commission requiring testing of all new medicine in children. We certainly agree that this new proposal is a step forward in terms of developing evidence-based therapies for children. We also agree that the creation of a new Paediatric Committee is an opportunity for the scientific community to influence the direction …
Predictors of Chronic Obstructive Pulmonary Disease Exacerbation Reduction in Response to Daily Azithromycin Therapy
Authors: MeiLan K. Han, Nabihah Tayob, Susan Murray, Mark T. Dransfield, George Washko, Paul D. Scanlon, Gerard J. Criner, Richard Casaburi, John Connett, Stephen C. Lazarus, Richard Albert, Prescott Woodruff, Fernando J. Martinez
Journal: American Journal of Respiratory and Critical Care Medicine (2014)

Daily azithromycin decreases acute exacerbations of chronic obstructive pulmonary disease (AECOPD), but long-term side effects are unknown.To identify the types of exacerbations most likely to be reduced and clinical subgroups most likely to benefit from azithromycin, 250 mg daily, added to usual care.Enrollment criteria included irreversible airflow limitation and AECOPD requiring corticosteroids, emergency department visit, or hospitalization in the prior year or use of supplemental oxygen. Recurrent events and cumulative incidence analyses compared treatment received for AECOPD by randomization group, stratified by subgroups of interest. Cox proportional hazards models estimated treatment effects in subgroups adjusted for age, sex, smoking status, FEV1% predicted, concomitant COPD medications, and oxygen use.Azithromycin was most effective in reducing AECOPD requiring both antibiotic and steroid treatment (n = 1,113; cumulative incidence analysis, P = 0.0002; recurrent events analysis, P = 0.002). No difference in treatment response by sex (P = 0.75), presence of chronic bronchitis (P = 0.19), concomitant inhaled therapy (P = 0.29), or supplemental oxygen use (P = 0.23) was observed. Older age and milder Global Initiative for Chronic Obstructive Lung Disease stage were associated with better treatment response (P = 0.02 and 0.04, respectively). A significant interaction between treatment and current smoking was seen (P = 0.03) and azithromycin did not reduce exacerbations in current smokers (hazard ratio, 0.99; 95% confidence interval, 0.71-1.38; P = 0.95).Azithromycin is most effective in preventing AECOPD requiring both antibiotic and steroid treatment. Adjusting for confounders, we saw no difference in efficacy by sex, history of chronic bronchitis, oxygen use, or concomitant COPD therapy. Greater efficacy was seen in older patients and milder Global Initiative for Chronic Obstructive Lung Disease stages. We found little evidence of treatment effect among current smokers. Clinical trial registered with www.clinicaltrials.gov (NCT0011986 and NCT00325897).
Antibodies against β-Amyloid Slow Cognitive Decline in Alzheimer's Disease
Authors: Christoph Hock, Uwe Konietzko, Johannes R Streffer, Jay Tracy, Andri Signorell, Britta Müller-Tillmanns, Ulrike Lemke, Katharina Henke, Eva Moritz, Esmeralda Garcia, M.Axel Wollmer, Daniel Umbricht, Dominique J.F de Quervain, Marc Hofmann, Alessia Maddalena, Andreas Papassotiropoulos, Roger M Nitsch
Journal: Neuron (2003)
Pulmonary oedema in paraquat poisoning
Authors: A. J. S. Gardiner
Journal: Thorax (1972)

This is the case report of a 47-year-old man who swallowed a powerful commercial herbicide containing paraquat. He developed oral, oesophageal, renal, and hepatic damage and, at an earlier stage than is usual, severe pulmonary changes from which he made a satisfactory recovery. The disordered pulmonary function and production of pulmonary oedema fluid in this patient are attributed to interference with surfactant activity in the lung.
Whose lung is it anyway?
Authors: T Treasure
Journal: Thorax (2002)

Should the decision to operate be made by patients with NSCLC or their doctors?

The central point of the argument in the paper by Dowie and Wildman in this issue of Thorax 1 is that it is the patient, not the doctors, who should decide whether to take the risk of an operation in the hope of curing lung cancer. I agree, and I know from working with a number of chest physicians on a regular basis that the patient's preference is genuinely central in decisions made about treatment. What is less certain is whether the choices being made are as explicit and as fully informed as would be necessary to implement decision analysis as espoused in this paper.2 My purpose is to ground the ideas in the context of current clinical practice and to see how near or far we are from patient determined decision making.

Firstly, the diagnosis must be known—including stage and cell type—and an estimate of prognosis made before the decision table can be entered. Dowie and Wildman's starting point is stage Ia non-small cell lung cancer. Clinicians will know that preoperative staging is never certain (if it were, we could claim a 100% surgical cure rate for N0M0 disease), but with increasing use of FDG-PET (fluoro-deoxyglucose positron emission tomography) in addition to CT scanning and mediastinoscopy as appropriate, we get as near to a diagnosis of stage Ia disease as is currently possible.

We must also tell the patient. There are strategies for “breaking bad news” and it is never easy; it is we, the clinicians, who have to do it, but do it we must.3 In current practice not telling the patient can rarely be justified and we cannot have a decision analysis based on “gradual disclosure”4 and other forms of …
Anticancer immunochemotherapy using adjuvants with direct cytotoxic effects
Authors: Laurence Zitvogel, Guido Kroemer
Journal: Journal of Clinical Investigation (2009)

Conventional chemotherapeutics may induce immunogenic cancer cell death or stimulate immune effectors via so-called off-target effects. The study by Besch et al. in this issue of the JCI now demonstrates that agents designed to stimulate the innate immune system by activating intracellular pattern recognition receptors can kill cancer cells in a direct, cell-autonomous fashion (see the related article beginning on page 2399). The authors show that ligation of viral RNA sensors, such as RIG-I or MDA-5, by viral RNA mimetics triggers mitochondrial apoptosis in human melanoma cells in an IFN-independent fashion. The data suggest that tumor cell killing and immunostimulation may synergize for optimal anticancer immunochemotherapy.
Sequenced Compared With Simultaneous Anthracycline and Cyclophosphamide in High-Risk Stage I and II Breast Cancer: Final Analysis From INT-0137 (S9313)
Authors: Hannah M. Linden, Charles M. Haskell, Stephanie J. Green, C. Kent Osborne, George W. Sledge, Charles L. Shapiro, James N. Ingle, Danika Lew, Laura F. Hutchins, Robert B. Livingston, Silvana Martino
Journal: Journal of Clinical Oncology (2007)

Purpose We conducted a phase III randomized study of two adjuvant treatment schedules of doxorubicin (A) and cyclophosphamide (C) in early-stage breast cancer to determine if administration of sequential single agents (A → C) results in superior disease-free survival (DFS) and overall survival (OS) versus the same total dose given in combination (AC). Patients and Methods High-risk node-negative or low-risk node-positive breast cancer patients received AC given: (arm I) concurrently (AC) doxorubicin 54 mg/m 2 and cyclophosphamide 1.2 g/m 2 intravenously (IV) every 3 weeks for six cycles; or (arm II) in sequence (A → C) doxorubicin 40.5 mg/m 2 IV days 1 and 2 every 3 weeks for four cyles followed by cyclophosphamide 2.4 gm/m 2 IV every 2 weeks for three cycles. Total dose and duration were identical, but the intensity of each drug was increased on A → C. Both arms included granulocyte colony-stimulating factor support and prophylactic antibiotics. All but premenopausal women with receptor negative tumors received tamoxifen after chemotherapy. Results Between 1994 and 1997, 3,176 patients were randomly assigned. Arms were well balanced; 48% of eligible patients were node-negative and 48% were estrogen receptor–positive. No significant differences in OS or DFS were observed; 5-year estimates of OS (95% CI) were 88% (87% to 90%) on AC and 89% (87% to 91%) on A → C. Grade 4 hematologic toxicity was greater on A → C, but nonhematological grade 4 was similar. Conclusion The overall result does not support superiority of dose-intense sequenced single agents. The greater toxicity of higher doses of single agents does not support their sequential use.
Recurrent tuberculosis from 1992 to 2004 in a metropolitan area
Authors: J. Cacho, A. Pérez Meixeira, I. Cano, T. Soria, A. Ramos Martos, M. Sánchez Concheiro, S. Samper, P. Gavin, C. Martín
Journal: European Respiratory Journal (2007)

The proportion of recurrent tuberculosis (TB) cases caused by re-infection has varied widely in previous studies. The aim of the present study was to determine the relative frequency of relapse and exogenous re-infection in patients with second episodes of TB, using DNA fingerprinting. A population-based retrospective longitudinal descriptive study was conducted in Madrid (Spain) during 1992–2004. The study consisted of 645 patients with culture-confirmed TB. Of these, 20 (3.1%) were retained because they presented with a second isolate of Mycobacterium tuberculosis . Finally, 12 of these cases were excluded because they did not complete the full treatment prescribed. All strains were typed by restriction fragment length polymorphism analysis and some by mycobacterial interspersed repetitive unit-variable number of tandem repeats analysis. The patients with recurrent TB were compared with those without recurrent TB. For seven out of the eight patients, the restriction fragment length polymorphism patterns of the Mycobacterium tuberculosis strains from the episodes of recurrent disease showed identical initial and final genotypes, indicating relapse; the remaining recurrent case showed different genotypes, suggesting exogenous re-infection. Re-infection is possible among people in developed countries, but the rates are lower than those occurring in high-risk areas. The risk factors for recurrent tuberculosis should be taken into account in the follow-up of treatment and tuberculosis control strategies.
Prevention of Hypoglycemia While Achieving Good Glycemic Control in Type 1 Diabetes
Authors: Paolo Rossetti, Francesca Porcellati, Geremia B. Bolli, Carmine G. Fanelli
Journal: Diabetes Care (2008)

Insulin therapy in diabetes, both at onset and after several years’ duration, is primarily directed to maintain near-normoglycemia to prevent the onset and/or delay progression of long-term complications (1,2). However, it is important that regimens of insulin therapy are designed not only to aim at near-normalizing blood glucose, but also to minimize the risk of hypoglycemia. Subjects with type 1 diabetes continuously drift between hyperglycemia and hypoglycemia. If the former prevails, long-term complications are frequently expected (1). On the other hand, hypoglycemia is not only dangerous and unpleasant, but may over time lead to the syndrome of hypoglycemia unawareness (3).

This is relevant in type 1 diabetes but also in type 2 diabetes, since over time, many type 2 diabetic subjects develop progressive pancreatic β-cell dysfunction requiring insulin therapy. Because in subjects with advanced type 2 diabetes the neuroendocrine responses to hypoglycemia are as abnormal as in type 1 diabetic patients (4), insulin therapy may become responsible for frequent and/or severe hypoglycemia in type 2 diabetic patients as well.

The goal of minimizing the risk of hypoglycemia while achieving good glycemic control is feasible as long as 1 ) a rational plan of insulin therapy is adopted, 2 ) blood glucose is properly monitored, 3 ) blood glucose targets are individualized, and 4 ) education programs are widely implemented.

In the present article, the importance of the use of insulin analogs as a key tool to achieve good glycemic control and prevent hypoglycemia is emphasized.

Normal nondiabetic subjects maintain plasma glucose <100 mg/dl in the fasting and <135 mg/dl in the postprandial period. In the fasting state, this is due to the continuous release of insulin from the pancreas, which results in steady plasma insulin, thus restraining hepatic glucose production and thereby preventing fasting hyperglycemia. At mealtime, the normal pancreas releases …
COMPENSATORY HYPERTROPHY OF THE LUNG AFTER UNILATERAL PNEUMECTOMY
Authors: T. Addis
Journal: The Journal of Experimental Medicine (1928)

In the albino rat the removal of the left lung, which constitutes about one-third of the total lung tissue, is followed by an average increase of more than 40 per cent in the mass of the remaining lung, as estimated from the nitrogen content of the almost blood-free tissue.
Furby not guilty as "charged"
Authors: G. Basky
Journal: BMJ (1999)

It seems now that Furby, last Christmas's “must have” stuffed toy with a computer chip inside, which was vilified for interfering with medical equipment, does not affect medical machinery after all.

An investigation by Health Canada (the government's health ministry), published recently in the Canadian Medical Association Journal (1999;161:971), revealed that the electric and magnetic fields given …
Determination of the histological distribution of insulin like growth factor 1 receptors in the rat gut.
Authors: J Ryan, D C Costigan
Journal: Gut (1993)

The histological distribution of insulin like growth factor 1 (IGF 1) receptors in the rat gut was studied. Immunostaining of IGF 1 receptors identified localisation on the villus epithelium, in the crypts, and in Brunner's glands of the small intestine. These tissues represent areas of high cell growth/differentiation, division, and macromolecular synthesis respectively, which constitute biological activities long associated with IGF 1. Cellular localisation of IGF 1 receptors was seen in the lamina propria by IGF 1 receptor immunostaining and ligand binding of biotinylated IGF 1. IGF 1 receptor immunostaining in the spleen showed receptor localisation to the splenic pulp thus pointing to macrophages as the possible IGF 1 receptor positive cells in the lamina propria. The results further implicate IGF 1 as an important growth factor in gut maintenance.
Good news, good news: occupational and household activities are important for energy expenditure, but sport and recreation remain the best buy for public health
Authors: Wendy Brown, Steven N Blair
Journal: British Journal of Sports Medicine (2012)

Data in the preceding editorial show that, across most of the adult lifespan, energy expenditure attributable to sport and recreation is much lower than that attributable to occupation. The editorial makes the point that most studies on the relationship between physical activity and health have focused largely on leisure-time activity, and may therefore be vulnerable to ‘missing important exposure information’.1

While this is true, we would do well to recall that the earliest studies of physical activity epidemiology relied primarily on measures of occupational physical activity, and that this field of research has now turned full circle, as outlined in our earlier review paper (from early roots in occupational sitting, through aerobic fitness training, then moderate-intensity physical activity, to a contemporary perspective on the balance between activity and inactivity in different domains of everyday life).2 It is also important to recall that all these studies showed relationships between physical activity …
High disease activity is associated with an increased risk of infection in patients with rheumatoid arthritis
Authors: K. Au, G. Reed, J. R. Curtis, J. M. Kremer, J. D. Greenberg, V. Strand, D. E. Furst
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Objective</h3> To determine the relationship of disease activity to infections in patients with rheumatoid arthritis (RA). <h3>Methods</h3> From the CORRONA database, the incidence of physician-reported infections in RA patients on stable disease-modifying antirheumatic drug, biological, and corticosteroid therapy for at least 6 months was ascertained. Two composite measures of disease activity were defined: clinical disease activity index (CDAI) and disease activity score 28 (DAS28). Incident rate ratios (IRR) were calculated using generalised estimating equation Poisson regression models adjusted for demographics, medications and clinical factors. <h3>Results</h3> Of 1 6242 RA patients, 6242 were on stable therapy for at least 6 months and were eligible for analysis. 2282 infections were reported in the cohort, followed over 7290 patient-years. After controlling for possible confounders, disease activity was associated with an increased rate of infections. Each 0.6 unit increase in DAS28 score corresponded to a 4% increased rate of outpatient infections (IRR 1.04, p=0.01) and a 25% increased rate of infections requiring hospitalisation (IRR 1.25, p=0.03). There was a dichotomy in the relationship between infections and CDAI scores. For CDAI &lt;10 (mild disease activity) patients had a 12% increased rate of outpatient infections with each 5 unit increase in CDAI score (IRR 1.12, p=0.003). At CDAI scores ≥10, there was no further increase in the rate of outpatient infections associated with higher disease activity. The relationship of CDAI to hospitalised infections showed similar trends to outpatient data but did not reach statistical significance after multivariate analysis (CDAI &lt;10: IRR 1.56, p=0.08). <h3>Conclusions</h3> In this large cohort of RA patients, higher disease activity was associated with a higher probability of developing infections.
The Effect of a Metalloproteinase Inhibitor (GI5402) on Tumor Necrosis Factor- (TNF-) and TNF- Receptors During Human Endotoxemia
Authors: Pascale E.P. Dekkers, Fanny N. Lauw, Tessa ten Hove, Anje A. te Velde, Philip Lumley, David Becherer, Sander J.H. van Deventer, Tom van der Poll
Journal: Blood (1999)
Unexplained Budd-Chiari syndrome in a young man
Authors: Leona Kim Schluger, Olcay Çubukçu, Franklin Klion, Swan N. Thung
Journal: Hepatology (1995)

CASE HISTORYan albumin level of 3.3 n/dL (normal = 3.4 to 5.2).The The patient was a 29-year-old man who was referred to the Mount Sinai Medical Center, New York, NY, for an evaluation of progressive ascites.He was healthy until 4 months before presentation at another hospital when he began to experience vague abdominal discomfort with progressive ascites refractory to diuretic therapy and a 30-lb weight loss.Serological testing and imaging procedures, which included an abdominal computed tomography scan and ultrasound were nondiagnostic.He underwent a percutaneous liver biopsy that was interpreted as showing congenital hepatic fibrosis.He was born in New York and had not traveled outside of the continental United States.He had worked managing a record store, cleaning swimming pools during the summer, and polishing marble goods.He had no known exposure to hepatotoxic chemicals.He had no history of alcohol abuse.He denied the use of anabolic steroids or other medications.There was no known family history of liver disease.On presentation to the Mount Sinai Medical Center 1 month later, he was cachectic with marked ascites and minimal peripheral edema.The liver was firm and nodular.The liver span was 15 cm by percussion and no bruit was auscultated.The spleen was not palpable.There were no stigmata of chronic liver disease.He was awake and alert without asterixis.Laboratory data showed a white blood cell count of 9.6 X lo3 (normal = 4.8 x lo3 to 10.8 x lo3), hematocrit level of 23.5% (normal = 42% to 55%), a platelet count of 430 X lo3/ mm3 (normal = 150 x lo3 to 450 x lo3), and a prothrombin time of 13.3 seconds (normal = 11.0 to 13.2).The serum bilirubin was 1.3 mg/dL (normal = 0.1 to 1.2)' alkaline phosphatase activity was 365 U/L (normal = 30 to 1001, aspartate transaminase activity was 78 U/L (normal = 1 to 501, and alanine transaminase activity was 125 U/L (normal = 1 to 53).The total serum protein was 6.4 g/dL (normal = 6.0 t o 8.3) with
Clinical outcome of continuous ambulatory peritoneal dialysis predicted by urea and creatinine kinetics.
Authors: J C Brandes, W F Piering, J A Beres, S S Blumenthal, C Fritsche
Journal: Journal of the American Society of Nephrology (1992)

The effectiveness of urea kinetics (Kt/V, where K is urea clearance, t is treatment time, and V is the volume of distribution for urea) to assess the adequacy of continuous ambulatory peritoneal dialysis (CAPD) and clinical outcome has not been established prospectively, and cross-sectional clinical studies have been inconclusive. A minimum weekly creatinine clearance of 40 to 50 L is recommended, but the adequacy of this dose is unproven. We introduced a simpler approach to creatinine kinetics in the form of an efficacy number (EN) calculated from data obtained in a standardized 4-h dwell exchange. To determine the most effective model for predicting CAPD adequacy, residual renal function, weekly Kt/V urea, weekly creatinine clearance standardized to body surface area, and EN (liters per gram of creatinine per day) were measured in 18 stable CAPD patients followed prospectively for at least 12 months. Patients were divided into three groups, good (G), intermediate (I), and poor (P), on the basis of uremic symptoms, mortality, hospital days, biochemical indices, and the need for transfer to hemodialysis. When comparing groups G (N = 6) and P (N = 8), weekly Kt/V were 2.3 +/- 0.2 versus 1.5 +/- 0.1 (P less than 0.005), weekly creatinine clearances were 71.5 +/- 8.6 versus 35.1 +/- 1.3 L (P less than 0.001), and EN were 7.4 +/- 0.8 versus 3.6 +/- 0.2 L/g of creatinine/day (P less than 0.005). Creatinine kinetics (weekly clearance and EN) but not urea kinetics could differentiate group I (N = 4) from groups G or P. Both urea and creatinine kinetics predict clinical outcome in CAPD.(ABSTRACT TRUNCATED AT 250 WORDS)