tbuckley/cabot-search huggingface dataset:
Complications and competing risks of death in compensated viral cirrhosis (ANRS CO12 CirVir prospective cohort)
Authors: Jean‐Claude Trinchet, Valérie Bourcier, Cendrine Chaffaut, Mohand Ait Ahmed, Setty Allam, Patrick Marcellin, Dominique Guyader, Stanislas Pol, Dominique Larrey, Victor De Lédinghen, Denis Ouzan, Fabien Zoulim, Dominique Roulot, Albert Tran, Jean‐Pierre Bronowicki, Jean‐Pierre Zarski, Odile Goria, Paul Calès, Jean‐Marie Péron, Laurent Alric, Marc Bourlière, Philippe Mathurin, Jean‐Frédéric Blanc, Armand Abergel, Lawrence Serfaty, Ariane Mallat, Jean‐Didier Grangé, Catherine Buffet, Yannick Bacq, Claire Wartelle, Thông Dao, Yves Benhamou, Christophe Pilette, Christine Silvain, Christos Christidis, Dominique Capron, Gérard Thiefin, Sophie Hillaire, Vincent Di Martino, Pierre Nahon, Sylvie Chevret
Journal: Hepatology (2015)

Various critical events, liver related or not, occur in patients with compensated cirrhosis, but their respective burden remains to be prospectively assessed. The aim of this prospective cohort study involving 35 French centers was to capture the whole spectrum of complications occurring in compensated viral cirrhosis (VC) using competing risks analyses. Inclusion criteria were: histologically proven cirrhosis resulting from hepatitis C virus (HCV) or hepatitis B virus (HBV); Child‐Pugh A; and no previous hepatic complications. The cohort was considered as a multistate disease model, cumulative incidences (CumIs) of events were estimated in a competing risks framework. A total of 1,654 patients were enrolled from 2006 to 2012 (HCV, 1,308; HBV, 315; HCV‐HBV, 31). During a median follow‐up of 34 months, at least one liver nodule was detected in 271 patients, confirmed as hepatocellular carcinoma (HCC) in 128 (4‐year cumI: 10.5%) and cholangiocarcinoma in 3. HCC incidence was higher in HCV (4‐year cumI: 11.4% vs. 7.4%; P = 0.05). HCC fulfilled Milan criteria in 79.3%, leading to curative treatment in 70.4%. Liver decompensation occurred more frequently in HCV patients (4‐year cumI: 10.8% vs. 3.6%; P = 0.0004). Virological eradication/control was achieved in 34.1% of HCV and 88.6% of HBV patients and was associated with a marked decrease in HCC, decompensation, and bacterial infection incidences. Survival was shorter in HCV patients (4‐year cumI: 91.6% vs. 97.2%; P = 0.0002). Death (n = 102; missing data: 6) was attributed to liver disease in 48 (47%; liver cancer: n = 18; miscellaneous, n = 30) and extrahepatic causes in 48 (47%; bacterial infection: n = 13; extrahepatic cancers: n = 10; cardiovascular events: n = 5; miscellaneous, n = 20). Conclusion : After 3 years of follow‐up, extrahepatic events still explained half of deaths in patients with compensated VC. A strong decrease in complications was linked to virological eradication/control. (H epatology 2015;62:737–750)
Abstract No. 2 Prevalences of the chronic idiopathic and metabolic photodermatoses in Scotland
Authors: R.S. Dawe
Journal: British Journal of Dermatology (2006)

We have attempted to estimate the prevalence of the idiopathic photodermatoses (except the usually seasonal polymorphic light eruption and juvenile spring eruption) and the cutaneous porphyrias in Scotland. Knowledge of the prevalence of these conditions may be useful (i) for planning care for our population, and (ii) because knowledge of prevalences in our population, compared with other populations, might help us to determine factors likely to be important in causing these disorders. The Photobiology Unit holds a database of patients assessed between 1978 and now. For this study the database was searched in January 2003. We have estimated population prevalences based on the assumptions (i) that we have investigated all patients with these conditions who live in appropriate catchment areas, (ii) that the population of these areas is as recorded in the 2001 Census, and (iii) that our local database accurately lists patients who are still alive and in our area. We estimated prevalences (per 100 000) as follows: chronic actinic dermatitis 16·5 (binomial ‘exact’ 95% confidence interval 13·7–19·7), porphyria cutanea tarda 7·6 (3·8–13·5), idiopathic solar urticaria 3·9 (2·6–5·6), actinic prurigo 3·3 (2·1–4·8), erythropoietic protoporphyria 2·3 (1·3–3·7), variegate porphyria 0·54 (0·15–1·4), hydroa vacciniforme 0·47 (0·03–0·71) and erythropoietic porphyria 0·04 (0·0048–0·14). Ideally, prevalences of these conditions should be determined by a population survey, or the use of capture-recapture methods. However, neither of these approaches is practical for these rare conditions for which there are not multiple comprehensive diagnostic databases. Our approach, despite all its flaws, gives better estimates than have until now been available for prevalences of most of these conditions. Acknowledgment and Disclaimer: Orfagen (France) provided funding for this study. This study has not been previously published but has been presented at a meeting of the Scottish Dermatological Society.
A HISTORY OF THE DEVELOPMENT OF THE CONCEPT OF FUNCTIONAL NERVOUS DISEASE DURING THE PAST TWENTY-FIVE HUNDRED YEARS
Authors: A. WARREN STEARNS
Journal: American Journal of Psychiatry (1946)

In perspective it is obvious that a relationship between psyche and soma has been observed during the whole history of medicine. Until well within the last one hundred years no one conceived of nervousness in terms other than visceral disease. During the past hundred years there has been increasing emphasis upon the importance of psychological manifestations of illness until, at the high point of this interest the soma was almost forgotten. The tide has receded until now the interest is in the interrelations of physical and mental factors. The difference is that early physicians thought in terms of visceral disease as causing nervous manifestation, while today we have reversed the trend and think of visceral disorder in terms of nervous disease. Reflection upon the history of medical thought may be profitable. The best minds of medicine have struggled with these disorders and contemporary fashion has been accepted as ultimate truth. The excellent descriptions show powers of observation of the highest quality, but the interpretation and the treatment are entirely matters of contemporary philosophy. To quote Lecky: The doctrine, that the opinions of a given period are mainly determined by the intellectual condition of society, and that every great change of opinion is the consequence of general causes, simply implies that there exists a strong bias which acts upon all large masses of men, and eventually triumphs over every obstacle. The inequalities of civilisation, the distorting influences arising out of special circumstances, the force of conservatism, and the efforts of individual genius, produce innumerable diversities; but a careful examination shows that these are but the eddies of an advancing stream, that the various systems are being all gradually modified in a given direction, and that a certain class of tendencies appears with more and more prominence in all departments of intellect. Nervous exhaustion, anemia, cerebral hyperemia, auto-intoxication, focal infection, glandular dysfunction, and psychogenesis have their day and then disappear except as matters of medical curiosity. This should lead us to a cautious, temperate and critical evaluation of present-day thought, in order that we may avoid, through excessive confidence, belief that the last hypothesis represents the ultimate truth.
Differential Regurgitation in Branch Pulmonary Arteries After Repair of Tetralogy of Fallot
Authors: I-Seok Kang, Andrew N. Redington, Leland N. Benson, Christopher Macgowan, Emanuela R. Valsangiacomo, Kevin Roman, Christian J. Kellenberger, Shi-Joon Yoo
Journal: Circulation (2003)

The importance of pulmonary regurgitation (PR) after repair of tetralogy of Fallot (TOF) is increasingly recognized, but little is known regarding its underlying mechanisms. This phase-contrast cine magnetic resonance (PC MR) study was performed to evaluate the relative contribution of each lung to total regurgitant volume.Twenty-two patients with significant PR underwent a PC MR 3 to 16 years after repair of TOF. Regurgitant fraction of the main pulmonary artery was 39+/-10%. Regurgitant fraction of the left pulmonary artery (LPA; 46+/-18%) was greater than that of the right pulmonary artery (34+/-16%; P=0.002). The average contribution of the LPA to the total regurgitant flow volume was 54+/-19%, whereas its average contribution to the total forward flow volume was 44+/-13% (P=0.002). In 4 patients, regurgitant flow in the LPA accounted for 75% to 100% of the total regurgitant flow. There was a linear relationship between regurgitant fraction and fraction of the regurgitant flow duration in the main pulmonary artery (P<0.001) and right pulmonary artery (P=0.001) but not in the LPA (P=0.129).PR after repair of TOF is commonly associated with differential regurgitation in the branch pulmonary arteries, which is usually greater in the LPA. Although the cause of this disparity requires further investigation, those patients with a significant unilateral contribution to total PR may be amenable to localized techniques to reduce regurgitation.
Reduction in Stroke With Gemfibrozil in Men With Coronary Heart Disease and Low HDL Cholesterol
Authors: Hanna Bloomfield Rubins, John Davenport, Viken Babikian, Lawrence M. Brass, Dorothea Collins, Laura Wexler, Stephen Wagner, Vassilios Papademetriou, Gale Rutan, Sander J. Robins
Journal: Circulation (2001)

Background —A low level of HDL cholesterol has been identified as a risk factor for stroke in observational studies. Methods and Results —Our objective was to determine whether treatment aimed at raising HDL cholesterol and lowering triglycerides reduces stroke in men with coronary heart disease and low levels of both HDL and LDL cholesterol. The study was a placebo-controlled, randomized trial conducted in 20 Veterans Affairs medical centers. A total of 2531 men with coronary heart disease, with mean HDL cholesterol 0.82 mmol/L (31.5 mg/dL) and mean LDL cholesterol 2.9 mmol/L (111 mg/dL), were randomized to gemfibrozil 1200 mg/d or placebo and were followed up for 5 years. Strokes were confirmed by a blinded adjudication committee. Relative risks were derived from Cox proportional hazards models. There were 134 confirmed strokes, 90% of which were ischemic. Seventy-six occurred in the placebo group (9 fatal) and 58 in the gemfibrozil group (3 fatal), for a relative risk reduction, adjusted for baseline variables, of 31% (95% CI, 2% to 52%, P =0.036). The reduction in risk was evident after 6 to 12 months. Patients with baseline HDL cholesterol below the median may have been more likely to benefit from treatment than those with higher HDL cholesterol. Conclusions —In men with coronary heart disease, low HDL cholesterol, and low LDL cholesterol, gemfibrozil reduces stroke incidence.
Addressing the Controversy: Do Bisphosphonates Directly Affect Primary Tumors?
Authors: Julie A. Sterling
Journal: Cancer Discovery (2015)

Abstract Summary: The recent article by Junankar and colleagues focuses on demonstrating the uptake of bisphosphonates (BP) into the primary tumor in both animal models and human samples. Interestingly, the authors were able to establish tumor-associated macrophages as the cell type that takes up the BPs. These studies are an important advancement for understanding the potential benefits of using BPs as adjuvant therapy in patients with cancer. Cancer Discov; 5(1); 14–5. ©2015 AACR. See related article by Junankar and colleagues, p. 35
Glomerulopathy in Patient With Donohue Syndrome (Leprechaunism)
Authors: Eileen N Ellis, Stephen F Kemp, J Paul Frindik, M Jocelyn Elders
Journal: Diabetes Care (1991)

Objective To evaluate renal structure in a child with Donohue syndrome (leprechaunism), who at 10 yr of age was noted to have hypertension, microalbuminuria, and enlarged kidneys, a renal biopsy was performed. Research Design And Methods The renal biopsy tissue was evaluated by light and electron microscopy with standard stereological techniques to measure glomerular volume, glomerular basement membrane width, fractional mesangial volume, and peripheral capillary filtering surface density. Results On renal biopsy, there was a marked increase in glomerular volume, glomerular basement width, and mesangial volume, findings similar to those seen in patients with diabetic nephropathy. Conclusions This patient with marked insulin resistance associated with Donohue syndrome demonstrates renal and glomerular enlargement and morphometric glomerular changes similar to those seen in patients with diabetic nephropathy. In unusual syndromes with hyperglycemia and hyperinsulinemia, renal structural and functional changes typical of traditional diabetes mellitus may be seen.
Hygroscopic condenser humidifiers in chronically tracheostomized patients who breathe spontaneously
Authors: M Vitacca, E Clini, K Foglio, S Scalvini, S Marangoni, A Quadri, N Ambrosino
Journal: European Respiratory Journal (1994)

The aim of this study was to test the usefulness of hygroscopic condenser humidifiers on secretion and on inspired gas temperature in tracheostomized patients. Forty spontaneously breathing chronically tracheostomized patients were divided into two groups: Group 1 received a hygroscopic condenser humidifier connected to the tracheostomy, 24 h daily for 10 days; Group 2, without any protection system, was chosen as the control group. The daily number of tracheal suctions, quantity of aspirate and thickness and colouring of secretions was evaluated. At baseline, and at days 5 and 10, patients were submitted to blood gas analysis, respiratory function tests and sputum analysis. The temperature of gases breathed was measured at rest and during a hyperventilation test, with and without the hygroscopic condenser humidifier. Statistically significant differences were found in thickness and colouring of secretions between the two groups during the period of 10 days. Group 2 showed a significantly greater trend in number of bacteria than Group 1. The group with the hygroscopic condenser humidifier showed respiratory function improvement over time for forced expiratory volume in one second (FEV1) and tidal volume (VT), maximal inspiratory pressure (MIP), and maximal voluntary ventilation (MVV) in comparison to the control group, who did not. Significant differences in the temperature between rest and hyperventilation, with and without a hygroscopic condenser humidifier were also found. In conclusion, a hygroscopic condenser humidifier may be useful in chronically tracheostomized patients who breathe spontaneously, improving viscosity and colouring of secretions, preventing further bacterial colonization, heating inspiratory flow, and helping to improve the functional outcome.
Cytokines. 2. Cytokines and lung inflammation: mechanisms of neutrophil recruitment to the lung.
Authors: R M Strieter, N W Lukacs, T J Standiford, S L Kunkel
Journal: Thorax (1993)

Inflammation within the lung represents the host's response to several insults including trauma, infection, autoimmune disorders, adult respiratory distress syndrome (ARDS) associated with sepsis or multiorgan failure, cancer, allograft rejection, and ischaemia reperfusion injury.Although historically the lung has been perceived as an organ primarily involved in gas exchange, its role in mediating host defence has only recently been appreciated.The airway, with its mucociliary clear- ance and the extensive alveolar capillary membrane composed of both immune and non-immune cells, functions as an important barrier against inhaled and haematogenous challenges.The pulmonary response to these inflammatory stimuli ultimately affects host survival since the lung must maintain its structural integrity for gas exchange.The capacity of the lung to generate an acute inflammatory response is necessary to ensure adequate clearance of offending agents.For example, the host response to a bacterial pneumonitis is characterised by a fulminate, acute inflammatory reaction.The histopathology of this pneumonia is com- posed of proteinaceous exudate and massive neutrophil infiltration leading to consolida- tion of the lung.Once the inciting agent is cleared, the inflammatory reaction resolves and normal repair and tissue remodelling occurs.This re-establishes normal lung func- tion without the development of chronic pulmonary fibrosis.In contrast, an exuberant acute inflammatory reaction such as ARDS may culminate in severe lung injury which ultimately affects host survival.Although the basic mechanisms operative in mediating this acute pulmonary inflammation remain to be fully elucidated, the participation of both immune and non-immune cells in the genera- tion of reactive oxygen metabolites, lipids, and protein mediators of inflammation are essential to the full expression of this inflam- matory response.In this review we will focus on recent advances in inflammation research that address mechanisms of cytokine induced neutrophil recruitment into the lung during the pathogenesis of acute pulmonary inflam- mation.
Microdystrophin Gene Therapy of Cardiomyopathy Restores Dystrophin-Glycoprotein Complex and Improves Sarcolemma Integrity in the <i>Mdx</i> Mouse Heart
Authors: Yongping Yue, Zhenbo Li, Scott Q. Harper, Robin L. Davisson, Jeffrey S. Chamberlain, Dongsheng Duan
Journal: Circulation (2003)

Background— More than 90% of Duchenne muscular dystrophy (DMD) patients develop cardiomyopathy, and many die of cardiac failure. Despite tremendous progress in skeletal muscle gene therapy, few attempts have been made to treat cardiomyopathy. Microdystrophin genes are shown to correct skeletal muscle pathological lesions in the mdx mouse model for DMD. Here, we tested the therapeutic potential of adeno-associated virus (AAV)–mediated microdystrophin gene therapy in the mdx mouse heart. Methods and Results— AAV was delivered to the newborn mdx mouse cardiac cavity. The procedure was rapid and well tolerated. Efficient expression was achieved in the inner and the outer layers of the myocardium. The ubiquitous cytomegalovirus promoter resulted in substantially higher expression than the muscle-specific CK6 promoter. The therapeutic effects of microdystrophin were evaluated at 10 months after infection. Immunostaining demonstrated extensive microdystrophin expression and successful restoration of the dystrophin-glycoprotein complex. Importantly, AAV-mediated microdystrophin expression improved the sarcolemma integrity in the mdx heart. Conclusions— We established a simple gene transfer method for efficient and persistent transduction of the mdx mouse heart. AAV-mediated microdystrophin expression restored the critical dystrophin-glycoprotein complex and improved sarcolemma integrity of the mdx heart. Our results revealed the promise of AAV-microdystrophin gene therapy for cardiomyopathy in DMD.
Treatment of hairy cell leukemia with cladribine(2-chlorodeoxyadenosine) by subcutaneous bolus injection:a phase II study
Authors: A. von Rohr, S.-F. H. Schmitz, A. Tichelli, U. Hess, D. Piguet, M. Wernli, N. Frickhofen, G. Konwalinka, G. Zulian, M. Ghielmini, B. Rufener, C. Racine, M.F. Fey, T. Cerny, D. Betticher, A. Tobler
Journal: Annals of Oncology (2002)
Absence of Troponin I Degradation or Altered Sarcoplasmic Reticulum Uptake Protein Expression After Reversible Ischemia in Swine
Authors: Salome A. Thomas, James A. Fallavollita, Te-Chung Lee, Jun Feng, John M. Canty
Journal: Circulation Research (1999)

The findings of troponin I (TnI) proteolysis (in isolated rat hearts) and induction of selected sarcoplasmic reticulum (SR) calcium-regulatory genes (after repetitive total coronary occlusions in swine) have given rise to the hypothesis that the time course of functional recovery of stunned myocardium reflects the resynthesis of reversibly damaged proteins. Although stunning occurs after brief total occlusions and prolonged partial occlusions (ie, short-term hibernation), the time course of functional recovery varies from a few hours to several days, suggesting that the severity of protein damage or mechanisms responsible for the dysfunction may differ. To study this, we examined SR gene expression and TnI degradation in stunned myocardium produced by 10-minute total left anterior descending coronary artery (LAD) occlusions (n=4) or 1-hour partial LAD occlusions, in which flow was reduced to approximately 50% of control values for 60 minutes (n=6) in swine. One hour after reperfusion, LAD wall thickening was severely depressed in both models despite normal perfusion and no triphenyltetrazolium chloride evidence of necrosis. Normal myocardium exhibited TnI immunoreactivity at 31 kDa and a weak secondary band at 27 kDa. Irreversible injury or calpain activation in vitro produced a marked increase in the intensity of the 27-kDa band, consistent with TnI degradation. Stunned myocardium demonstrated no change in the 31- or the 27-kDa band, and the percentage of the 27- to 31-kDa band remained constant after 10-minute total occlusions (LAD, 5.9+/-0.9%; normal, 4.9+/-1.6%) and 1-hour partial occlusions (LAD, 8.5+/-1.9%; normal, 7.3+/-1.4%) and in sham controls (LAD, 10.9+/-1.5%; normal, 9.8+/-1.4%). Northern analysis showed no alterations in TnI or SR gene expression, but the stress protein HSP-70 was variably induced. Thus, stunned myocardium occurs without TnI degradation or altered SR gene expression, indicating that additional mechanisms are responsible for the reversible dysfunction after single episodes of regional ischemia in swine.
Mucosal inhibition of cholinergic contractions in ferret trachea can be transferred between organ baths
Authors: A Ullman, CG Lofdahl, N Svedmyr, L Bernsten, BE Skoogh
Journal: European Respiratory Journal (1988)

The influence of the mucosa on the contractile responses to cholinergic nerve stimulation in an in vitro nerve muscle preparation of ferret trachea was studied. Repeated contractions were induced by alternating direct vagal nerve stimulation (DNS) and electrical field stimulation (EFS). With intact mucosa there was a marked successive decrease of the contractile responses. During 60 minutes the responses decreased to 46 +/- 8% of baseline (Mean +/- SEM, n = 6), compared to 86 +/- 2% in preparations, in which the mucosa was initially removed. The mucosa dependent inhibition could be partly blocked by indomethacin (10 microM). The inhibitory effect could be transferred via the bath fluid from a donor preparation with intact mucosa to a recipient preparation with removed mucosa. Fluid transferred from a donor preparation with removed mucosa or from indomethacin treated preparations did not affect the contractile responses in the recipient preparation. We conclude that ferret tracheal mucosa can release a factor which inhibits the contractile responses to cholinergic nerve stimulation. The release of this factor can be blocked to a major part by indomethacin and the factor can be transferred from a donor to a recipient preparation.