tbuckley/cabot-search huggingface dataset:
Susceptibility testing and resistance phenotype detection in<i>Staphylococcus aureus</i>strains isolated from patients with atopic dermatitis, with apparent and recurrent skin colonization
Authors: A. Kędzierska, M. Kapińska-Mrowiecka, M. Czubak-Macugowska, K. Wójcik, J. Kędzierska
Journal: British Journal of Dermatology (2008)

Staphylococcus aureus colonization is accepted to be an important triggering factor in patients with atopic dermatitis (AD) and antibiotic resistance has been recognized to be a serious problem as a consequence and for the management of AD treatment.To investigate the antibiotic resistance pattern of S. aureus strains isolated from patients with AD with apparent (lesional and nonlesional skin areas) and recurrent skin colonization and strains obtained from healthy nasal carriers.Eighty-seven patients (age 23+/-11.5 years) with mild to severe AD (SCORAD 46.9+/-16.6), 21 patients (age 19.8+/-6.7 years) before antistaphylococcal treatment and 177 healthy nasal carriers (age 27.5+/-8.4 years) were microbiologically assessed for carriage of S. aureus. Colonization of lesional and nonlesional skin areas was quantified by counting the number of colony forming units on the skin surface (log(10) CFU cm(-2)). Antimicrobial susceptibility and resistance phenotypes of 179 S. aureus strains were assessed with the agar disc-diffusion method.Staphylococcus aureus was isolated from 87% of lesional and 44% of nonlesional skin samples from patients with AD. The colonization density of S. aureus was markedly higher in lesional than in nonlesional skin (P<0.001), and was positively correlated with AD severity (P<0.001) and total serum IgE (P<0.05). Patients with AD had a significantly higher prevalence of chloramphenicol-resistant S. aureus than nasal carriers (P<0.01). Similar rates of resistance were expressed to tetracycline, erythromycin, mupirocin, clindamycin and penicillin. Nearly 35% of S. aureus strains from the lesional skin demonstrated different antimicrobial sensitivity pattern compared with strains from nonlesional skin of the same patients with AD. The trend of increasing resistance to chloramphenicol, erythromycin and fusidic acid was observed among S. aureus strains recovered from patients after approximately 75 days of antibiotic treatment. Methicillin-resistant S. aureus isolates were cultured from two patients, one during exacerbation and the other after subsequent bacterial recolonization.Discrepancies in antibiotic sensitivity pattern were observed among S. aureus strains colonizing different sites of AD skin (lesional and nonlesional areas), and also in AD patients with prior antibiotic treatment. Therefore, clinicians should consider repeat microbial susceptibility testing on different body sites of patients with AD when clinically indicated.
Development of anaplastic lymphoma kinase (ALK) small‐molecule inhibitors for cancer therapy
Authors: Rongshi Li, Stephan W. Morris
Journal: Medicinal Research Reviews (2007)

Abstract Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase (RTK) involved in the genesis of several human cancers; indeed, ALK was initially identified in constitutively activated and oncogenic fusion forms—the most common being nucleophosmin (NPM)‐ALK—in a non‐Hodgkin's lymphoma (NHL) known as anaplastic large‐cell lymphoma (ALCL) and subsequent studies identified ALK fusions in the human sarcomas called inflammatory myofibroblastic tumors (IMTs). In addition, two recent reports have suggested that the ALK fusion, TPM4‐ALK, may be involved in the genesis of a subset of esophageal squamous cell carcinomas. While the cause‐effect relationship between ALK fusions and malignancies such as ALCL and IMT is very well established, more circumstantial links implicate the involvement of the full‐length, normal ALK receptor in the genesis of additional malignancies including glioblastoma, neuroblastoma, breast cancer, and others; in these instances, ALK is believed to foster tumorigenesis following activation by autocrine and/or paracrine growth loops involving the reported ALK ligands, pleiotrophin (PTN) and midkine (MK). There are no currently available ALK small‐molecule inhibitors approved for clinical cancer therapy; however, recognition of the variety of malignancies in which ALK may play a causative role has recently begun to prompt developmental efforts in this area. This review provides a succinct summary of normal ALK biology, the confirmed and putative roles of ALK fusions and the full‐length ALK receptor in the development of human cancers, and efforts to target ALK using small‐molecule kinase inhibitors. © 2007 Wiley Periodicals, Inc. Med Res Rev, 28, No. 3, 372–412, 2008
Tobacco Smoke Carcinogens and Lung Cancer
Authors: S. S. Hecht
Journal: JNCI Journal of the National Cancer Institute (1999)

The complexity of tobacco smoke leads to some confusion about the mechanisms by which it causes lung cancer. Among the multiple components of tobacco smoke, 20 carcinogens convincingly cause lung tumors in laboratory animals or humans and are, therefore, likely to be involved in lung cancer induction. Of these, polycyclic aromatic hydrocarbons and the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone are likely to play major roles. This review focuses on carcinogens in tobacco smoke as a means of simplifying and clarifying the relevant information that provides a mechanistic framework linking nicotine addiction with lung cancer through exposure to such compounds. Included is a discussion of the mechanisms by which tobacco smoke carcinogens interact with DNA and cause genetic changes—mechanisms that are reasonably well understood—and the less well defined relationship between exposure to specific tobacco smoke carcinogens and mutations in oncogenes and tumor suppressor genes. Molecular epidemiologic studies of gene-carcinogen interactions and lung cancer—an approach that has not yet reached its full potential—are also discussed, as are inhalation studies of tobacco smoke in laboratory animals and the potential role of free radicals and oxidative damage in tobacco-associated carcinogenesis. By focusing in this review on several important carcinogens in tobacco smoke, the complexities in understanding tobacco-induced cancer can be reduced, and new approaches for lung cancer prevention can be envisioned.
Overnight salivary caffeine clearance: A liver function test suitable for routine use
Authors: Gerhard Jost, Axel Wahlländer, Ursula Von Mandach, Rudolf Preisig
Journal: Hepatology (1987)

The feasibility of measuring caffeine clearance from saliva (SCI) was assessed in ambulatory patients with liver disease and in a control group, and the results were compared with quantitative liver function tests. For this purpose, the subjects were given 280 mg caffeine p.o. in decaffeinated coffee powder between noon and 4 p.m., and caffeine concentrations were measured in saliva (using an enzyme immunoassay) before bedtime and upon arising. In the cirrhotics (n = 29), SCI was 0.58 ± S.D. 0.45 ml per min × kg, thus being reduced to approximately one-third of drug-free, nonsmoking controls (1.53 ± 0.46, n = 18); although patients with non-cirrhotic liver disease showed intermediate values (0.95 ± 0.47), their reduction in SCI was significant (p &lt; 0.001). SCI was correlated with indocyanine green fractional clearance, galactose elimination capacity and aminopyrine breath test; however, the closest relationship (R s = 0.80) was observed with the aminopyrine breath test. It is suggested that the measurement of SCI represents a noninvasive and innocuous procedure for quantifying hepatic microsomal function, and is suitable for routine use. Since a.m. saliva concentrations of caffeine are highly correlated (R s = −0.94) with SCl, further simplification of the test to a single-point measurement appears possible.
CXCR2- and E-Selectin–induced Neutrophil Arrest during Inflammation In Vivo
Authors: Michael L. Smith, Timothy S. Olson, Klaus Ley
Journal: The Journal of Experimental Medicine (2004)

The signaling events leading to the activation of integrins and firm arrest of rolling neutrophils in inflamed venules have yet to be elucidated. In vitro assays suggest that both E-selectin and chemokines can trigger arrest of rolling neutrophils, but E-selectin−/− mice have normal levels of adherent neutrophils in inflamed venules. To test whether chemokine-induced neutrophil arrest in vivo can be unmasked by blocking E-selectin, we investigated neutrophil adhesion in inflamed cremaster muscle venules in tumor necrosis factor (TNF)-α–treated CXCR2−/− or wild-type (WT) mice injected with E-selectin blocking monoclonal antibody (mAb) 9A9. To block chemokine receptor signaling, we investigated E-selectin−/− or WT mice treated with pertussis toxin (PTx) intravenously. Neutrophil adhesion was unchanged in CXCR2−/−, E-selectin−/−, PTx-treated WT, or mAb 9A9–treated WT mice. However, TNF-α–induced neutrophil adhesion was almost completely abrogated in E-selectin−/− mice treated with PTx and significantly reduced in CXCR2−/− mice treated with the E-selectin blocking mAb. In thioglycollate-induced peritonitis, PTx treatment blocked neutrophil recruitment into the peritoneum of E-selectin−/− mice, but had only a partial effect in WT animals. These data show that E-selectin– and chemokine-mediated arrest mechanisms are overlapping in this model and identify CXCR2 as an important neutrophil arrest chemokine in vivo.
Bradykinin Signaling Counteracts cAMP-Elicited Aquaporin 2 Translocation in Renal Cells
Authors: Grazia Tamma, Monica Carmosino, Maria Svelto, Giovanna Valenti
Journal: Journal of the American Society of Nephrology (2005)

Bradykinin (BK) is one of the most important peptides regulating vascular tone, water, and ionic balance in the body, playing a key role in controlling BP. It is interesting that patients with essential hypertension excrete less BK than normotensive individuals. For elucidating the mechanism by which BK regulates renal water transport that contributes to its antihypertensive effect, aquaporin 2 (AQP2)-transfected collecting duct CD8 cells, expressing the BK type II receptor (BK2R), were used as an experimental model. In CD8 cells, BK pretreatment impaired forskolin-induced AQP2 translocation to the apical plasma membrane. For clarifying the signal transduction cascade associated with this effect, whether BK induced an increase in cytosolic calcium, via the G protein Gq, known to be coupled to BK2R, first was investigated. Spectrofluorometry using fura-2-AM revealed that 100 nM BK elicited a significant increase in Cai, which was abolished by the receptor antagonist HOE-140. BK acts through BK2R coupled to both Gq and Gα13, a known upstream effector of Rho protein. In CD8 cells, BK causes an increase in Rho activity, likely as a result of Gα13 activation. This results in stabilization of the cortical F-actin network, thus impairing AQP2 trafficking. These effects counteract physiologic vasopressin stimulation, which instead has an opposite effect on actin network organization through Rho inactivation.
Improved ventilatory response at peak exercise despite no change in peak oxygen consumption with chronic beta-blockade in heart failure patients
Authors: Eugene E. Wolfel, Tatiana O. Tsvetkova, Brain D. Lowes, JoAnn Lindenfeld, Simon F. Shakar, William T. Abraham, Alastair D. Robertson, Edward M. Gilbert, Michael R. Bristow
Journal: Journal of the American College of Cardiology (2002)
Efficient Cancer Therapy with a Nanobody-Based Conjugate
Authors: Virna Cortez-Retamozo, Natalija Backmann, Peter D. Senter, Ullrich Wernery, Patrick De Baetselier, Serge Muyldermans, Hilde Revets
Journal: Cancer Research (2004)

Nanobodies are the smallest fragments of naturally occurring single-domain antibodies that have evolved to be fully functional in the absence of a light chain. Nanobodies are strictly monomeric, very stable, and highly soluble entities. We identified a nanobody with subnanomolar affinity for the human tumor-associated carcinoembryonic antigen. This nanobody was conjugated to Enterobacter cloacae beta-lactamase, and its site-selective anticancer prodrug activation capacity was evaluated. The conjugate was readily purified in high yields without aggregation or loss of functionality of the constituents. In vitro experiments showed that the nanobody-enzyme conjugate effectively activated the release of phenylenediamine mustard from the cephalosporin nitrogen mustard prodrug 7-(4-carboxybutanamido) cephalosporin mustard at the surface of carcinoembryonic antigen-expressing LS174T cancer cells. In vivo studies demonstrated that the conjugate had an excellent biodistribution profile and induced regressions and cures of established tumor xenografts. The easy generation and manufacturing yield of nanobody-based conjugates together with their potent antitumor activity make nanobodies promising vehicles for new generation cancer therapeutics.
Extracorporeal Membrane Oxygenation for Pandemic Influenza A(H1N1)–induced Acute Respiratory Distress Syndrome
Authors: Tài Pham, Alain Combes, Hadrien Rozé, Sylvie Chevret, Alain Mercat, Antoine Roch, Bruno Mourvillier, Claire Ara-Somohano, Olivier Bastien, Elie Zogheib, Marc Clavel, Adrien Constan, Jean-Christophe Marie Richard, Christian Brun-Buisson, Laurent Brochard
Journal: American Journal of Respiratory and Critical Care Medicine (2012)

Many patients with severe acute respiratory distress syndrome (ARDS) caused by influenza A(H1N1) infection receive extracorporeal membrane oxygenation (ECMO) as a rescue therapy.To analyze factors associated with death in ECMO-treated patients and the influence of ECMO on intensive care unit (ICU) mortality.Data from patients admitted for H1N1-associated ARDS to French ICUs were prospectively collected from 2009 to 2011 through the national REVA registry. We analyzed factors associated with in-ICU death in ECMO recipients, and the potential benefit of ECMO using a propensity score-matched (1:1) cohort analysis.A total of 123 patients received ECMO. By multivariate analysis, increasing values of age, lactate, and plateau pressure under ECMO were associated with death. Of 103 patients receiving ECMO during the first week of mechanical ventilation, 52 could be matched to non-ECMO patients of comparable severity, using a one-to-one matching and using control subjects only once. Mortality did not differ between the two matched cohorts (odds ratio, 1.48; 95% confidence interval, 0.68-3.23; P = 0.32). Interestingly, the 51 ECMO patients who could not be matched were younger, had lower Pa(o(2))/Fi(o(2)) ratio, had higher plateau pressure, but also had a lower ICU mortality rate than the 52 matched ECMO patients (22% vs. 50%; P < 0.01).Under ECMO, an ultraprotective ventilation strategy minimizing plateau pressure may be required to improve outcome. When patients with severe influenza A(H1N1)-related ARDS treated with ECMO were compared with conventionally treated patients, no difference in mortality rates existed. The unmatched, severely hypoxemic, and younger ECMO-treated patients had, however, a lower mortality.
Improved regional myocardial blood flow, left ventricular unloading, and infarct salvage using an axial-flow, transvalvular left ventricular assist device. A comparison with intra-aortic balloon counterpulsation and reperfusion alone in a canine infarction model.
Authors: R W Smalling, D B Cassidy, R Barrett, B Lachterman, P Felli, J Amirian
Journal: Circulation (1992)

BACKGROUND It has been suggested that left ventricular unloading at the time of reperfusion provides superior infarct salvage over reperfusion alone. The purpose of this study was to show that the Hemopump transvalvular axial-flow left ventricular assist device provides superior left ventricular unloading, ischemic zone collateral blood flow, and infarct size reduction compared with intra-aortic balloon counterpulsation and reperfusion alone. METHODS AND RESULTS Eighteen dogs were instrumented with regional myocardial function sonomicrometers in the ischemic and control zones. The left anterior descending coronary artery just distal to the first diagonal branch was instrumented with a silk snare and Doppler flow probe. Additionally, pressure catheters were placed in the left atrial appendage, left ventricular apex, and ascending aorta for hemodynamic measurements. Regional myocardial blood flow was determined by using 15-microns radioactive microspheres. Measurements were made in the control state, immediately after coronary occlusion, at 1 and 2 hours after coronary occlusion, with reperfusion, and 1 hour after reperfusion. In treated animals, left ventricular assistance was maintained during the entire period of occlusion and reperfusion. The Hemopump was associated with a significant decrease in left ventricular systolic and diastolic pressure, whereas mean arterial pressure was maintained. Intra-aortic balloon counterpulsation resulted in no significant changes in left ventricular systolic pressure and a modest decrease in left ventricular diastolic pressure. Regional unloading as assessed by sonomicrometers was significant in the Hemopump animals and absent in the balloon pump animals. Absolute regional myocardial blood flow in the ischemic zone increased slightly (p = 0.002) in the Hemopump animals and did not change in the balloon pump animals. Infarct size expressed as percentage of the zone at risk was 62.6% in the control animals, 27.22% in the balloon pump animals, and 21.7% in the Hemopump animals. CONCLUSIONS Mechanical unloading of the ventricle during ischemia and reperfusion appears to result in significant infarct salvage compared with reperfusion alone. The Hemopump appears to provide superior left ventricular systolic and diastolic unloading compared with intra-aortic counterpulsation in a canine model.
Serum and red blood cell magnesium, copper, and zinc content in G6PD deficiency
Authors: R. Karunanithy, S. E. Ng, N. Saha
Journal: American Journal of Hematology (1990)

Abstract Sixty‐nine G6PD‐deficient and 67 normal non‐deficient Chinese adult males were investigated for blood hemoglobin concentration and for serum and red cell content of magnesium, copper, and zinc. There was no significant difference in blood hemoglobin content. Both the serum magnesium and copper content were found to be significantly lower in the G6PD‐deficient subjects compared to that in the non‐deficient control. Serum zinc content and red cell content of all the three metals were not significantly altered in G6PD deficiency.
First-Line Gefitinib in Patients With Advanced Non–Small-Cell Lung Cancer Harboring Somatic <i>EGFR</i> Mutations
Authors: Lecia V. Sequist, Renato G. Martins, David Spigel, Steven M. Grunberg, Alexander Spira, Pasi A. Jänne, Victoria A. Joshi, David McCollum, Tracey L. Evans, Alona Muzikansky, Georgiana L. Kuhlmann, Moon Han, Jonathan S. Goldberg, Jeffrey Settleman, A. John Iafrate, Jeffrey A. Engelman, Daniel A. Haber, Bruce E. Johnson, Thomas J. Lynch
Journal: Journal of Clinical Oncology (2008)

Somatic mutations in the epidermal growth factor receptor (EGFR) correlate with increased response in patients with non-small-cell lung cancer (NSCLC) treated with EGFR tyrosine kinase inhibitors (TKIs). The multicenter iTARGET trial prospectively examined first-line gefitinib in advanced NSCLC patients harboring EGFR mutations and explored the significance of EGFR mutation subtypes and TKI resistance mechanisms.Chemotherapy-naïve patients with advanced NSCLC with >or= 1 clinical characteristic associated with EGFR mutations underwent direct DNA sequencing of tumor tissue EGFR exons 18 to 21. Patients found to harbor any EGFR mutation were treated with gefitinib 250 mg/d until progression or unacceptable toxicity. The primary outcome was response rate.Ninety-eight patients underwent EGFR screening and mutations were detected in 34 (35%). EGFR mutations were primarily exon 19 deletions (53%) and L858R (26%) though 21% of mutation-positive cases had less common subtypes including exon 20 insertions, T790M/L858R, G719A, and L861Q. Thirty-one patients received gefitinib. The response rate was 55% (95% CI, 33 to 70) and median progression-free survival was 9.2 months (95% CI, 6.2 to 11.8). Therapy was well tolerated; 13% of patients had grade 3 toxicities including one grade 3 pneumonitis. Two patients with classic activating mutations exhibited de novo gefitinib resistance and had concurrent genetic anomalies usually associated with acquired TKI resistance, specifically the T790M EGFR mutation and MET amplification.First-line therapy with gefitinib administered in a genotype-directed fashion to patients with advanced NSCLC harboring EGFR mutations results in very favorable clinical outcomes with good tolerance. This strategy should be compared with combination chemotherapy, the current standard of care.
Childhood Abuse in Patients With Conversion Disorder
Authors: Karin Roelofs, Ger P.J. Keijsers, Kees A.L. Hoogduin, Gérard W.B. Näring, Franny C. Moene
Journal: American Journal of Psychiatry (2002)

Despite the fact that the assumption of a relationship between conversion disorder and childhood traumatization has a long history, there is little empirical evidence to support this premise. The present study examined this relation and investigated whether hypnotic susceptibility mediates the relation between trauma and conversion symptoms, as suggested by Janet's autohypnosis theory of conversion disorder.A total of 54 patients with conversion disorder and 50 matched comparison patients with an affective disorder were administered the Structured Trauma Interview as well as measures of cognitive (Dissociative Experiences Scale) and somatoform (20-item Somatoform Dissociation Questionnaire) dissociative experiences.Patients with conversion disorder reported a higher incidence of physical/sexual abuse, a larger number of different types of physical abuse, sexual abuse of longer duration, and incestuous experiences more often than comparison patients. In addition, within the group of patients with conversion disorder, parental dysfunction by the mother-not the father-was associated with higher scores on the Dissociative Experiences Scale and the Somatoform Dissociation Questionnaire. Physical abuse was associated with a larger number of conversion symptoms (Structured Clinical Interview for DSM-IV Axis I Disorders). Hypnotic susceptibility proved to partially mediate the relation between physical abuse and conversion symptoms.The present results provide evidence of a relationship between childhood traumatization and conversion disorder.
Mitral valvotomy in childhood
Authors: M. S. Gotsman, R. L. Van Der Horst, B. T. le Roux, M. A. Williams
Journal: Thorax (1973)

<b>Gotsman, M. S., van der Horst, R. L., le Roux, B. T., and Williams, M. A. (1973)</b>. <i>Thorax</i>, 453-457. <b>Mitral valvotomy in childhood</b>. During the seven-year period 1965 to 1972 mitral valvotomy for mitral stenosis was undertaken in 72 children aged 15 years or less. Excellent results were achieved from closed transventricular instrumental valvotomy unless the valve was calcified, there was a jet of mitral incompetence or a second valvotomy was being undertaken. Severe pulmonary arterial hypertension was present before operation and regressed after a successful valvotomy. There was a low incidence of overt antecedent rheumatic fever.