tbuckley/cabot-search huggingface dataset:
Transthoracic needle aspiration biopsy for the diagnosis of localised pulmonary lesions: a meta-analysis
Authors: Y. Lacasse, E. Wong, G. H Guyatt, D. J Cook
Journal: Thorax (1999)

<h3>BACKGROUND</h3> Persisting controversy surrounds the use of transthoracic needle aspiration biopsy (TNAB) stemming from its uncertain diagnostic accuracy. A systematic review and meta-analysis was therefore conducted to evaluate the accuracy of TNAB for the diagnosis of solitary or multiple localised pulmonary lesions. <h3>METHODS</h3> Searches for English literature papers in Index Medicus (1963–1965) and Medline (1966–1996) were performed and the bibliographies of the retrieved articles were systematically reviewed. Articles evaluating the accuracy of TNAB in series of consecutive patients presenting with solitary or multiple pulmonary lesions were considered. Only papers in which ⩾90% of patients were given a final diagnosis according to an appropriate reference standard were included in the meta-analysis. <h3>RESULTS</h3> A total of 48 studies were included and five meta-analyses were conducted according to four diagnostic thresholds. From the pooled sensitivity and specificity corresponding to each diagnostic threshold, associated likelihood ratios (LRs) were derived for malignant disease as follows: (1) malignant versus all other categories, LR = 72; (2) malignant or suspicious versus all others, LR = 49; (3) suspicious versus all categories but malignant, LR = 15; (4) benign versus all others, LR = 0.07; and (5) specific benign diagnosis versus all others, LR = 0.005. Differences in methodological quality of the studies, needle types, or whether a cytopathologist participated in the procedure failed to explain the heterogeneity of the results found in almost every meta-analysis. Given a 50% probability of malignancy prior to the TNAB, post-test probabilities of malignancy upon receiving the results would be malignant, 99%; suspicious, 94%; non-specific benign, 7%; and benign with a specific diagnosis, 0.6%. <h3>CONCLUSIONS</h3> Given the intermediate pre-test probabilities that would probably lead to performing TNAB, findings of "malignant" or of a specific diagnosis of a benign condition provide definitive results. Findings of "suspicious" markedly increase the probability of malignancy, and "benign" markedly decreases it but may not be considered definitive.
Liver repopulation with bone marrow derived cells improves the metabolic disorder in the Gunn rat
Authors: M Muraca, C Ferraresso, M T Vilei, A Granato, M Quarta, E Cozzi, M Rugge, K A Pauwelyn, M Caruso, I Avital, D Inderbitzin, A A Demetriou, S J Forbes, G Realdi
Journal: Gut (2007)

<h3>Background:</h3> Reversible ischaemia/reperfusion (I/R) liver injury has been used to induce engraftment and hepatic parenchymal differentiation of exogenous β2-microglubulin<sup>−</sup>/Thy1<sup>+</sup> bone marrow derived cells. <h3>Aim:</h3> To test the ability of this method of hepatic parenchymal repopulation, theoretically applicable to clinical practice, to correct the metabolic disorder in a rat model of congenital hyperbilirubinaemia. <h3>Methods and results:</h3> Analysis by confocal laser microscopy of fluorescence labelled cells and by immunohistochemistry for β2-microglubulin, 72 hours after intraportal delivery, showed engraftment of infused cells in liver parenchyma of rats with I/R, but not in control animals with non-injured liver. Transplantation of bone marrow derived cells obtained from GFP-transgenic rats into Lewis rats resulted in the presence of up to 20% of GFP positive hepatocytes in I/R liver lobes after one month. The repopulation rate was proportional to the number of transplanted cells. Infusion of GFP negative bone marrow derived cells into GFP positive transgenic rats resulted in the appearance of GFP negative hepatocytes, suggesting that the main mechanism underlying parenchymal repopulation was differentiation rather than cell fusion. Transplantation of wild type bone marrow derived cells into hyperbilirubinaemic Gunn rats with deficient bilirubin conjugation after I/R damage resulted in 30% decrease in serum bilirubin, the appearance of bilirubin conjugates in bile, and the expression of normal UDP-glucuronyltransferase enzyme evaluated by polymerase chain reaction. <h3>Conclusions:</h3> I/R injury induced hepatic parenchymal engraftment and differentiation into hepatocyte-like cells of bone marrow derived cells. Transplantation of bone marrow derived cells from non-affected animals resulted in the partial correction of hyperbilirubinaemia in the Gunn rat.
Modulators of the protein kinase C system influence biliary excretion of cationic drugs
Authors: Herman Steen, Hans Smit, Almar Nijholt, Marjolijn Merema, Dirk K. F. Meijer
Journal: Hepatology (1993)

To investigate whether hepatobiliary transport of organic cations is under regulatory control, we studied transport of tri-n-butylmethylammonium in the isolated perfused rat liver and in isolated rat hepatocytes. Transport was investigated in the presence of modulators of the protein kinase C and the cyclic AMP second-messenger system. In the isolated perfused rat liver, it was observed that compounds modulating protein kinase C activity clearly affected the biliary excretion process of the cation tri-n-butylmethylammonium. Phorbol 12-myristate 13-acetate, a compound that directly stimulates protein kinase C, elevated the biliary excretion rate of tri-n-butylmethylammonium in a concentration-dependent manner, reaching a twofold increase at 60 nmol/L of the phorbol ester. The inactive derivative 4 alpha-phorbol 12, 13-didecanoate (60 nmol/L) did not show any effect. Vasopressin (48 nmol/L), a receptor-mediated activator of protein kinase C, stimulated the excretion rate of the cation by about 50%. Staurosporin (1 mumol/L), an inhibitor of protein kinase C, clearly decreased the biliary excretion rate of the cation and also blocked its stimulation by phorbol 12-myristate 13-acetate. Neither phorbol 12-myristate 13-acetate nor vasopressin (at concentrations ranging from 10(-9) to 10(-6) mol/L) affected the initial uptake velocity of tri-n-butylmethylammonium in isolated hepatocytes and isolated perfused livers, whereas staurosporin (1 mumol/L) showed only a modest inhibition of the uptake of the cation. It is inferred that the effect of protein kinase C modulators on hepatobiliary transport of organic cations occurs at the level of carrier-mediated transport in the canalicular membrane.(ABSTRACT TRUNCATED AT 250 WORDS)
Effect of propranolol in postinfarction patients with mechanical or electrical complications.
Authors: C D Furberg, C M Hawkins, E Lichstein
Journal: Circulation (1984)

In "post hoc" subgroup analyses, a simple classification system for patients, based on the presence or absence of findings indicative of electrical and/or mechanical complications early during short-term hospitalization, was applied to the data from the Beta-Blocker Heart Attack Trial (BHAT). In the largest subgroup of BHAT patients who had no reported complications, the 25 month mortality was low and the observed benefit of propranolol therapy small. Patients with electrical complications only had intermediate mortality and a pronounced effect of treatment was observed. Those with mechanical complications had the highest mortality and experienced an intermediate relative benefit of beta-blocker treatment. They also reported the most adverse effects. Post hoc analyses should always be interpreted cautiously. It is important to determine whether these findings are present in other completed beta-blocker trials. On the basis of these analyses alone it is suggested that the present practice of prescribing beta-blockers in postinfarction patients should not be altered.
INCREASED FIXATION OF SULFUR35 BY CARTILAGE IN VITRO FOLLOWING DEPLETION OF THE MATRIX BY INTRAVENOUS PAPAIN
Authors: T. F. McElligott, J. L. Potter
Journal: The Journal of Experimental Medicine (1960)

The uptake in vitro of sulfur-35 by costal cartilage obtained from nine rabbits 11 days after an intravenous injection of crude papain solution was compared with that in costal cartilage from eight normal untreated rabbits. An increased fixation of the isotope was found in treated animals compared with controls. The depletion of cartilage matrix by papain provided an experimental situation to test the hypothesis that the depletion of matrix which occurs in osteoarthritic cartilage can stimulate increased synthesis of chondroitin sulfate. The results give further support to the view that the primary lesion in osteoarthritis occurs in the matrix rather than in the chondrocyte of articular cartilage.
Selective serotonin reuptake inhibitors directly signal for apoptosis in biopsy-like Burkitt lymphoma cells
Authors: Adamantios Serafeim, Michelle J. Holder, Gillian Grafton, Anita Chamba, Mark T. Drayson, Quang T. Luong, Christopher M. Bunce, Christopher D. Gregory, Nicholas M. Barnes, John Gordon
Journal: Blood (2003)
FAMILIAL OUTBREAK OF PRIMARY HERPES INFECTION
Authors: P. M. INMAN, P. B. CRONE
Journal: British Journal of Dermatology (1971)

SUMMARY.— Within a few days of each other 3 sisters between the ages of 6 and 13, who were the only children of the family, all developed acute primary herpes. The 2 younger ones were ill with severe blistering of mouth and lips. The oldest child had gross blistering of the tongue, but only mild constitutional symptoms. Their father had suffered for years from recurrent herpes of lips.
Relation of Clinical Response and Minimal Residual Disease and Their Prognostic Impact on Outcome in Acute Myeloid Leukemia
Authors: Xueyan Chen, Hu Xie, Brent L. Wood, Roland B. Walter, John M. Pagel, Pamela S. Becker, Vicky K. Sandhu, Janis L. Abkowitz, Frederick R. Appelbaum, Elihu H. Estey
Journal: Journal of Clinical Oncology (2015)

Purpose Both presence of minimal residual disease (MRD) and achievement of complete remission (CR) with incomplete platelet recovery (CRp) rather than CR after induction therapy predict relapse in acute myeloid leukemia (AML). These results suggest a correlation between response (peripheral count recovery) and MRD at the time of morphologic remission. Here we examine this hypothesis and whether MRD and response provide independent prognostic information after accounting for other relevant covariates. Patients and Methods We retrospectively analyzed data from 245 adults with AML who achieved CR, CRp, or CR with incomplete blood count recovery (CRi) after induction therapy. Bone marrow samples were collected on or closest to the first date of blood count recovery, and MRD was determined by 10-color multiparameter flow cytometry. Results The 71.0% of patients who achieved CR had MRD less frequently and had lower levels of MRD than the 19.6% of patients achieving CRp and 9.4% achieving CRi. Although pretreatment covariates such as cytogenetics, monosomal karyotype, relapsed or refractory rather than newly diagnosed AML, and FLT3 internal tandem duplication were associated with relapse, their prognostic effect was much lower once MRD and response were taken into account, the univariable statistical effect of which was not materially affected by inclusion of pretreatment covariates. Conclusion Our data indicate that post-therapy parameters including MRD status and response are important independent prognostic factors for outcome in patients with AML achieving remission. MRD status and type of response (CR v CRp or CRi) should play important, and perhaps dominant, roles in planning postinduction therapy.
Inappropriate Activation of the Androgen Receptor by Nonsteroids: Involvement of the Src Kinase Pathway and Its Therapeutic Implications
Authors: Sonal J. Desai, Ai-Hong Ma, Clifford G. Tepper, Hong-Wu Chen, Hsing-Jien Kung
Journal: Cancer Research (2006)

Abstract The inappropriate activation of androgen receptor (AR) by nonsteroids is considered a potential mechanism in the emergence of hormone-refractory prostate tumors, but little is known about the properties of these “pseudoactivated” AR. Here, we present the first comprehensive analysis closely examining the properties of AR activated by the neuropeptide bombesin that distinguish it from androgen-activated AR. We show that bombesin-activated AR (a) is required for bombesin-induced growth of LNCaP cells, (b) has a transcriptional profile overlapping with, but not identical to, androgen-activated AR, (c) activates prostate-specific antigen by preferentially binding to its proximal promoter, and (d) assembles a distinct coactivator complex. Significantly, we found that Src kinase is critical for bombesin-induced AR-mediated activity and is required for translocation and transactivation of AR. Additionally, we identify c-Myc, a Src target gene, to be activated by bombesin and a potential coactivator of AR-mediated activity specific to bombesin-induced signaling. Because Src kinase is often activated by other nonsteroids, such as other neuropeptides, growth factors, chemokines, and cytokines, our findings have general applicability and provide rationale for investigating the efficacy of the Src kinase pathway as a target for the prevention of relapsed prostate cancers. (Cancer Res 2006; 66(21): 10449-59)
A puzzling presentation of pancreatitis
Authors: W Laleman, E Vanhoutte, D Vanbeckevoort, R Aerts, W Van Steenbergen, C Verslype
Journal: Gut (2008)

An 80-year old lady was admitted to the emergency department because of acute dyspnoea and orthopnoea. She reported no chest pain. Her previous medical history showed compensated congestive heart failure and a cholecystectomy for calculous …
Suppression of Arterial Thrombosis Without Affecting Hemostatic Parameters With a Cell-Penetrating PAR1 Pepducin
Authors: Ping Zhang, András Gruber, Shogo Kasuda, Carey Kimmelstiel, Katie O'Callaghan, Daniel H. Cox, Andrew Bohm, James D. Baleja, Lidija Covic, Athan Kuliopulos
Journal: Circulation (2012)

Thrombin-dependent platelet activation is heightened in the setting of percutaneous coronary intervention and may cause arterial thrombosis with consequent myocardial necrosis. Given the high incidence of adverse effects in patients with acute coronary syndromes, there remains an unmet need for the development of new therapeutics that target platelet activation without unduly affecting hemostasis. The thrombin receptor, PAR1, has recently emerged as a promising new target for therapeutic intervention in patients with acute coronary syndromes.We report the development of a first-in-class intracellular PAR1 inhibitor with optimized pharmacokinetic properties for use during percutaneous coronary intervention in patients with acute coronary syndromes. PZ-128 is a cell-penetrating pepducin inhibitor of PAR1 that targets the receptor-G-protein interface on the inside surface of platelets. The structure of PZ-128 closely resembles the predicted off-state of the corresponding juxtamembrane region of the third intracellular loop of PAR1. The onset of action of PZ-128 was rapid and suppressed PAR1 aggregation and arterial thrombosis in guinea pigs and baboons and strongly synergized with oral clopidogrel. There was full recovery of platelet function by 24 hours. Importantly, PZ-128 had no effect on bleeding or coagulation parameters in primates or in blood from patients undergoing percutaneous coronary intervention.Based on the efficacy data in nonhuman primates with no noted adverse effects on hemostasis, we anticipate that the rapid onset of platelet inhibition and reversible properties of PZ-128 are well suited to the acute interventional setting of percutaneous coronary intervention and may provide an alternative to long-acting small-molecule inhibitors of PAR1.
Citric acid cough threshold and airway responsiveness in asthmatic patients and smokers with chronic airflow obstruction.
Authors: B Auffarth, J G de Monchy, T W van der Mark, D S Postma, G H Koeter
Journal: Thorax (1991)

The relation between citric acid cough threshold and airway hyperresponsiveness was investigated in 11 non-smoking patients with allergic asthma (mean FEV1 94% predicted) and 25 non-atopic smokers with chronic airflow obstruction (mean FEV1 65% predicted). Cough threshold was determined on two occasions by administering doubling concentrations of citric acid. Seven of the 11 asthmatic subjects and 14 of 25 smokers with chronic airflow obstruction had a positive cough threshold on both test days. Cough threshold measurements were reproducible in both groups (standard deviation of duplicate measurements 1.2 doubling concentrations in asthma, 1.1 doubling concentrations in chronic airflow obstruction). Citric acid provocation did not cause bronchial obstruction in most patients, though four patients had a fall in FEV1 of more than 20% for a short time on one occasion only. No significant difference in cough threshold was found between the two patient groups despite differences in baseline FEV1 values. There was no significant correlation between cough threshold and the provocative concentration of histamine causing a 20% fall in FEV1 (PC20) histamine in either group. Thus sensory nerves can be activated with a tussive agent in patients with asthma and chronic airflow obstruction without causing bronchial smooth muscle contraction.
Rheumatoid arthritis (RA) patients have variable but comparable NLRP3-inflammasome induction to controls
Authors: C. Choulaki, E. Petraki, E. Choustoulaki, G. Goulielmos, D. Boumpas, P. Sidiropoulos
Journal: Annals of the Rheumatic Diseases (2010)

Data from animal models support an important role for interleukin 1b (IL1b) in the pathogenesis of rheumatoid arthritis (RA).1,2 NLRP3-inflammasome is one of the main cellular platforms for IL1b production upon activation by external or self danger signals.3 The authors The authors inflammasome in peripheral blood of patients with RA.

Heparin-anticoagulated whole blood from patients and healthy controls (HC) was used after red blood cell lysis. Monocytes were immunomagnetically isolated from peripheral blood mononuclear cells. TLR4 …
On the relationship between action potential duration and tension in cat papillary muscle
Authors: D. G. ALLEN
Journal: Cardiovascular Research (1977)

Tension and action potentials have been measured simultaneously from isolated cat papillary muscles. Two groups of experiments are described. In the first group, the external conditions under which the muscle contracted were changed. Specifically, stimulation rate, extracellular [Ca++, extracellular [Na++] were altered, and adrenaline was added to the bathing fluid. A tendency for given levels of tension to be accompanied by action potentials of constant duration is demonstrated under some of these conditions. In the second group of experiments, tension and action potentials were recorded following some change in external conditions; specifically, after a long rest, after a change in muscle length, and after the muscle had been set up in the experimental apparatus (the 'running-in' period). In the period that followed each of these interventions, peak tension increased substantially over at least several minutes but all external conditions (for example, temperature, muscle length, stimulation rate, and composition of the bathing fluid) remained constant. In each of these three situations tension increased but in one case the action potential duration increased, in another it decreased, and in the third it was unchanged. It is concluded that change in action potential durations do not necessarily make an important contribution to the changes in tension of papillary muscles.
Verapamil Results in Increased Blood Levels of Oncolytic Adenovirus in Treatment of Patients With Advanced Cancer
Authors: Anniina Koski, Mari Raki, Petri Nokisalmi, Ilkka Liikanen, Lotta Kangasniemi, Timo Joensuu, Anna Kanerva, Sari Pesonen, Ramon Alemany, Akseli Hemminki
Journal: Molecular Therapy (2011)

Calcium channel blockers including verapamil have been proposed to enhance release and antitumor efficacy of oncolytic adenoviruses in preclinical studies but this has not been studied in humans before. Here, we studied if verapamil leads to increased replication of oncolytic adenovirus in cancer patients, as measured by release of virions from tumor cells into the systemic circulation. The study was conducted as a matched case-control study of advanced cancer patients treated with oncolytic adenoviruses with or without verapamil. We observed that verapamil increased mean virus titers present in blood after treatment (P < 0.05). The frequency or severity of adverse events was not increased, nor were cytokine responses or neutralizing antibody levels different between groups. Signs of possible treatment-related clinical benefits were observed in both groups, but there was no significant difference in responses or survival. Thus, our data suggests that the combination of verapamil with oncolytic adenoviruses is safe and well tolerated. Moreover, verapamil treatment seems to result in higher virus titers in blood, indicating enhanced overall replication in tumors. A randomized trial is needed to confirm these findings and to study if enhanced replication results in benefits to patients.
Dark Regions of No-Reflow on Late Gadolinium Enhancement Magnetic Resonance Imaging Result in Scar Formation After Atrial Fibrillation Ablation
Authors: Christopher McGann, Eugene Kholmovski, Joshua Blauer, Sathya Vijayakumar, Thomas Haslam, Joshua Cates, Edward DiBella, Nathan Burgon, Brent Wilson, Alton Alexander, Marcel Prastawa, Marcos Daccarett, Gaston Vergara, Nazem Akoum, Dennis Parker, Rob MacLeod, Nassir Marrouche
Journal: Journal of the American College of Cardiology (2011)
Once-Daily Treatment With Beclomethasone Dipropionate Hydrofluoroalkane Nasal Aerosol (320 mcg/d) Provides Substantial Nasal Symptom Relief in Subjects With Perennial Allergic Rhinitis
Authors: B.M. Prenner, S. Weinstein, W. Pleskow, A. Tankelevich, Y. Ding, S.K. Tantry, P.M. Dorinsky
Journal: Journal of Allergy and Clinical Immunology (2012)