tbuckley/cabot-search huggingface dataset:
LYSOSOMAL AND ULTRASTRUCTURAL CHANGES IN HUMAN "TOXIC" NEUTROPHILS DURING BACTERIAL INFECTION
Authors: Charles E. McCall, Isao Katayama, Ramzi S. Cotran, Maxwell Finland
Journal: The Journal of Experimental Medicine (1969)

"Toxic" neutrophils from humans with severe bacterial infections, identified by the presence of Döhle bodies, "toxic" granules, and vacuoles were shown to differ from normal neutrophils both in ultrastructure and in lysosome activity. Döhle bodies were identified as lamellar aggregates of rough endoplasmic reticulum. Toxic granules corresponded to the azurophilic granules usually identified by Romanowsky stains only in neutrophil precursors. By electron microscopy such granules were large, electron-dense, and peroxidase positive; they could usually be distinguished from the smaller, less dense, "specific" granules also present in control neutrophils, but in the latter they became visible by light microscopy only after prolonged staining or following fixation with glutaraldehyde. These observations suggest that toxic granules represent an abnormal staining reaction of the large dense granules in the toxic cells, and not phagocytized material, newly formed abnormal granules or autophagic bodies. Alkaline phosphatase activity was significantly greater in toxic neutrophils than in normal ones; 80% of the activity of both was located in the lysosome fraction. Beta glucuronidase was normal. Total acid phosphatase was normal, but the percentage located in the nonlysosome fraction of toxic neutrophils was increased, suggesting that lysosomes were "labilized." Formation of neutral red vacuoles in supravitally stained preparations, an index of lysosome activity, occurred more rapidly in toxic neutrophils. This reaction paralleled degranulation and the formation of clear vacuoles in unstained wet mounts and could be blocked by colchicine, a lysosome stabilizer, or enhanced by procedures which activate lysosomes. "Autophagic" vacuoles were observed by electron microscopy in some toxic neutrophils. These observations are discussed in relation to the concept that the "toxic" neutrophils in severe bacterial infection reflect cellular immaturity and/or stimulation or degeneration.
The Health Insurance Portability and Accountability Act of 1996 (HIPAA) Privacy Rule: Implications for Clinical Research
Authors: Rachel Nosowsky, Thomas J. Giordano
Journal: Annual Review of Medicine (2005)

In the short time since it became effective for health care organizations, a privacy regulation issued under the Health Insurance Portability and Accountability Act of 1996 (HIPAA) has had a significant adverse impact on the conduct of clinical research in the United States, without a substantial corresponding increase in privacy protection for research participants. Some of the problems associated with HIPAA have been resolved through revisions since the regulation's initial promulgation in December 2000, and other problems can be addressed by better educating health care providers and researchers about its requirements and available alternatives for compliance; however, considerable structural challenges remain. These constitute substantial barriers to research and resulting medical advances. Additional revisions to HIPAA based on the principles and trade-offs reflected in the Common Rule-which responsibly balances an individual's interest in privacy protection with the public interest in gaining knowledge through biomedical research-can go a long way to remedying remaining flaws in the system.
Rituximab–EPOCH, an effective salvage therapy for relapsed, refractory or transformed B-cell lymphomas: results of a phase II study
Authors: M. Jermann, L.M. Jost, Ch. Taverna, E. Jacky, H.P. Honegger, D.C. Betticher, F. Egli, Th. Kroner, R.A. Stahel
Journal: Annals of Oncology (2004)
Inhibition of DOPA Decarboxylase in Vitro and in Vivo
Authors: WILLIAM G. CLARK, ROBERT S. POGRUND
Journal: Circulation Research (1961)

ARE NOW at least nine natu- rally occurring pharmacologically active amines in mammals that are formed by decarboxylation of their amino acid precursors.The reactions are listed below, together with relative rates of formation of the amines: 3, 4-Dihydroxyphenylalanine 3000 1 -2(DOPA) at nerve endings; is bound or stored there in inactive form inaccessible to degradative enzymes; is released and metabolized gradually in quiescence and massively during nerve activity; stimulates the effector; and then is destroyed rapidly.3, 4-Dihydroxyphenylethylamiiie 43 (Dopamine) 5-Hydroxytryptophan (5HTP) o-Tyrosine 4 m-Tyrosine Tryptophan 0 Phenylalanine 13 Tyrosine 9 ' "• 10 Histidine p-Hydroxyphenylserin e* 1000 1 300-5-Hydroxytryptamine *-(Serotonin, 5HT) 750 2 o-Tyramine 3 -6 -12 40 1 525 2 m-Tyramine 5 ' G> 7> 8 ' 12 30 2 Tryptamine 3 ' 7 ' 10 -"• 12 15 1 Phenylethylamine 5 ' 6 ' 12 2 2 Tvramine 5 ' 7 -«• 12 > 15 I 1 Histamine 17 >• ?p-Hydroxyphenylethanolamine 8 -1R *• (Octopamine)A large literature has been devoted to the physiological functions of these amines, and current work is being done.Many investigators believe that most, if not all, of them exert their effects on the cardiovascular and nervous system primarily by interaction with specialized chemical processes at synaptic junctions where nerve impulses are transmitted by release and diffusion of neurohumoral transmitters, such as acetylcholine and norepinephrine.A neurohumoral transmitter is thought of as a substance that is synthesized and found
Evidence for a Heritable Component in Death Resulting From Aortic and Mitral Valve Diseases
Authors: Benjamin D. Horne, Nicola J. Camp, Joseph B. Muhlestein, Lisa A. Cannon-Albright
Journal: Circulation (2004)

Cardiac valvular diseases contribute to >42,000 deaths yearly in the United States, but the role of genetics in these deaths is unknown. This study evaluated the familiality of death resulting from aortic, mitral, and all valvular diseases using a population-based genealogy linked to death records.The Utah Population Database contains >2 million individual records with genealogy data and 250,000 linked death certificates. Nonrheumatic aortic (n=932), mitral (n=1165), and all valvular (n=2504) disease deaths and rheumatic heart disease deaths (n=4713) were studied. Familial relative risks (FRRs) were assessed for first- and second-degree relatives. Familiality was also evaluated with the genealogical index of familiality, which considers all relationships in the Utah Population Database. FRRs were increased only for mitral valve death in both first-degree (FRR, 2.55; P<0.0001) and second-degree (FRR, 1.67; P<0.0001) relatives. Genealogical index of familiality analysis showed significant excess relatedness for all groups (P<0.001). Genealogical index of familiality results (P<0.001) for early age at death cases showed higher mean relatedness, a common characteristic of heritable disorders. Excess familiality extended to distant relatives for mitral (second-degree relatives) and aortic (beyond second-degree relatives) valve death.Deaths resulting from nonrheumatic mitral and aortic diseases clustered among both close and distant relatives, especially among early age at death cases, suggesting a significant genetic component in death resulting from valvular diseases. Future studies should focus on gene discovery.
Crucial role of nitric oxide synthases system in endothelium-dependent hyperpolarization in mice
Authors: Aya Takaki, Keiko Morikawa, Masato Tsutsui, Yoshinori Murayama, Ender Tekes, Hiroto Yamagishi, Junko Ohashi, Toyotaka Yada, Nobuyuki Yanagihara, Hiroaki Shimokawa
Journal: The Journal of Experimental Medicine (2008)

The endothelium plays an important role in maintaining vascular homeostasis by synthesizing and releasing several relaxing factors, such as prostacyclin, nitric oxide (NO), and endothelium-derived hyperpolarizing factor (EDHF). We have previously demonstrated in animals and humans that endothelium-derived hydrogen peroxide (H2O2) is an EDHF that is produced in part by endothelial NO synthase (eNOS). In this study, we show that genetic disruption of all three NOS isoforms (neuronal [nNOS], inducible [iNOS], and endothelial [eNOS]) abolishes EDHF responses in mice. The contribution of the NOS system to EDHF-mediated responses was examined in eNOS−/−, n/eNOS−/−, and n/i/eNOS−/− mice. EDHF-mediated relaxation and hyperpolarization in response to acetylcholine of mesenteric arteries were progressively reduced as the number of disrupted NOS genes increased, whereas vascular smooth muscle function was preserved. Loss of eNOS expression alone was compensated for by other NOS genes, and endothelial cell production of H2O2 and EDHF-mediated responses were completely absent in n/i/eNOS−/− mice, even after antihypertensive treatment with hydralazine. NOS uncoupling was not involved, as modulation of tetrahydrobiopterin (BH4) synthesis had no effect on EDHF-mediated relaxation, and the BH4/dihydrobiopterin (BH2) ratio was comparable in mesenteric arteries and the aorta. These results provide the first evidence that EDHF-mediated responses are dependent on the NOSs system in mouse mesenteric arteries.
Optical recordings in the rabbit heart show that defibrillation strength shocks prolong the duration of depolarization and the refractory period.
Authors: S M Dillon
Journal: Circulation Research (1991)

The present data were obtained using the technique of optical recording with the voltage-sensitive dye WW781. This technique, unlike electrical methods, was able to provide uninterrupted recordings free of artifacts during defibrillation shocks. Optical recordings were made from sites on the ventricular epicardium of perfused rabbit hearts during electrical pacing. Continuous recordings of the electrophysiological responses of an intact heart to defibrillation threshold-strength shocks were made. It was shown that these shocks were able to stimulate normal-appearing action potentials in nonrefractory myocardium. A new and unexpected finding was that defibrillation threshold-strength shocks were also able to evoke a sustained, depolarizing response from myocardium already undergoing an action potential. This prolonged the time that the myocardium remained in the depolarized state. Prolongation of the depolarized state was accompanied by an equal prolongation of the refractory period. There was no indication that this depolarizing shock response was due to damage of the myocardium by the shock, to heterogeneous electrical responses in the optical recording area, or to the methods used in this study. It is hypothesized that these shocks were able to elicit a new action potential in already depolarized myocardium by hyperpolarizing portions of the myocardium's cellular membranes and, in so doing, to reactivate the fast sodium current. This effect, if prevalent in a fibrillating ventricle, could play a role in the defribillation process by effectively resynchronizing electrical activity.
THE EFFECTS OF INDUCED FEVER ON CEREBRAL FUNCTIONS IN NEUROSYPHILIS
Authors: Albert Heyman, John L. Patterson, Fenwick T. Nichols
Journal: Journal of Clinical Investigation (1950)

Although fever is known to be associated with definite alterations in the circulation and metabo- lism of the body as a whole and of certain individual organs, there have been few observations on the changes occurring in the brain during fever.An increase in the cerebral arteriovenous oxygen difference was found in 15 patients with dementia paralytica during fever produced by typhoid vac- cine and inductotherm (1).It was suggested that the brain in these patients either responded to fever with a rise in metabolism greater than other parts of the body or else the cerebral blood flow is slower during fever, thus accounting for a larger arteriovenous difference.Looney and Borkovic (2), however, found a slight decrease in the cerebral oxygen arteriovenous difference in 12 patients with dementia paralytica undergoing diathermic fever treatment, but they did not be- lieve that these changes were significant.The oxygen consumption of brain tissue in vitro has been found to increase with temperature at levels lower than normal (3).At temperatures greater than normal, however, conflicting results have been obtained by different investigators (3, 4).The present report presents studies on the ef- fects of induced fever on the cerebral circulation and oxygen consumption in 27 patients with neurosyphilis.
Clinical and Neurobiological Correlates of Cytogenetic Abnormalities in Childhood-Onset Schizophrenia
Authors: Rob Nicolson, Jay N. Giedd, Marge Lenane, Susan Hamburger, Sujatha Singaracharlu, Jeffrey Bedwell, Tom Fernandez, Gunvant K. Thaker, Dolores Malaspina, Judith L. Rapoport
Journal: American Journal of Psychiatry (1999)

OBJECTIVE: Cytogenetic abnormalities are increased in schizophrenia, suggesting a possible etiologic contribution. However, their clinical and pathophysiologic roles in the disorder are unknown. To investigate this, a group of children and adolescents participating in a comprehensive study of childhood-onset schizophrenia were screened for chromosomal abnormalities, and their clinical and neurobiological correlates were examined. METHOD: Cytogenetic screening with the use of high-resolution banding, fluorescent in situ hybridization for chromosome 22q11 deletions, and molecular fragile X testing was undertaken in a group of 47 children and adolescents with very early onset of schizophrenia. Clinical, neurobiological (including brain morphometry), and risk factor measures of the subjects with cytogenetic abnormalities were compared with those of the remaining patients without ­cytogenetic anomalies. RESULTS: Five patients had previously undiagnosed cytogenetic ­abnormalities. Lower performance IQ and more pronounced premorbid developmental ­impairments were seen in this subgroup. Rates of obstetric complications, familial schizophrenia spectrum disorders, and familial eye tracking dysfunction were similar for the patients with and without cytogenetic abnormalities. CONCLUSIONS: Cytogenetic abnormalities appear to be increased in childhood-onset schizophrenia, suggesting an association with a very early age at onset. The data from the subgroup of patients with cytogenetic anomalies are consistent with a model in which a childhood onset of schizophrenia is due to a greater impairment of neurodevelopment secondary to the interaction of a number of factors, particularly genetic ones.
Ataluren for the treatment of nonsense-mutation cystic fibrosis: a randomised, double-blind, placebo-controlled phase 3 trial
Authors: Eitan Kerem, Michael W Konstan, Kris De Boeck, Frank J Accurso, Isabelle Sermet-Gaudelus, Michael Wilschanski, J Stuart Elborn, Paola Melotti, Inez Bronsveld, Isabelle Fajac, Anne Malfroot, Daniel B Rosenbluth, Patricia A Walker, Susanna A McColley, Christiane Knoop, Serena Quattrucci, Ernst Rietschel, Pamela L Zeitlin, Jay Barth, Gary L Elfring, Ellen M Welch, Arthur Branstrom, Robert J Spiegel, Stuart W Peltz, Temitayo Ajayi, Steven M Rowe
Journal: The Lancet Respiratory Medicine (2014)
Alternative Strategy to Achieve Increased Overall Survival and Better Quality of Life in Patients With Second-Line Advanced Non–Small-Cell Lung Cancer
Authors: Gary Spitzer, Mark A. Socinski
Journal: Journal of Clinical Oncology (2015)

TO THEEDITOR: Recent studies, including the article by Zer and Leighl 1 entitled “Second-Line Therapy in Non-Small-Cell Lung Cancer: The DELTA Between Different Genotypes Widens,” have suggested that chemotherapy is the best option for the treatment of patients with second-line advanced non–small-cell lung cancer (NSCLC) with wild-type (WT) epidermal growth factor receptor (EGFR). On the basis of the results of several randomized phase III clinical trials, pemetrexed, docetaxel, and erlotinib are all US Food and Drug Administration–approved therapies for use in this setting. ● The article by Zer and Leighl 1 states that the key goals of systemic therapy in advanced NSCLC are the improvement of symptoms, quality of life, and overall survival (OS) with minimal toxicity in the second-line setting in patients with WT EGFR. As part of this analysis, the authors discuss data that demonstrate the equivalence of EGFR tyrosine kinase inhibitors (TKIs) and chemotherapy in OS in nine randomized clinical trials. In contrast, further discussion centered on EGFR TKIs as inferior in patients with WT EGFR, using progression-free survival (PFS) and response from a recent meta-analysis 2 as their main argument. However, Lee et al discussed several flaws in their own comparison; most notably, several different lines of treatment were compared, the overall comparisons were not based on study randomization, and toxicity outcomes were not assessed. It should emphasized that the biology of tumor progression in a patient treated with platinum-doublet chemotherapy is different than biology of a chemotherapy-naive patient, and one cannot make the assumption that chemotherapy will be superior in a chemotherapy-treated EGFR WT patient group. Both the data from the meta-analysis 2 and from the Docetaxel and Erlotinib Lung Cancer Trial (DELTA) 3 concluded that although chemotherapy was associated with longer PFS as compared with EGFR TKI in patients with WT tumors, OS did not differ significantly between the groups. However, does PFS really address our key treatment goals for second-line treatment decisions? In this patient population, quality of life and OS should be primary end points and not PFS. Evidence for this viewpoint have previously been presented in Journal of Clinical Oncology (JCO). 4 We also point out that despite gains in PFS for patients receiving chemotherapy, the toxicity may be detrimental to OS. Finally, in a separate article in the same issue of JCO, Sacher et al 5 described the use of PFS as a surrogate for
Precipitation of nanohydroxyapatite on PLLA/PBLG/Collagen nanofibrous structures for the differentiation of adipose derived stem cells to osteogenic lineage
Authors: Rajeswari Ravichandran, Jayarama Reddy Venugopal, Subramanian Sundarrajan, Shayanti Mukherjee, Seeram Ramakrishna
Journal: Biomaterials (2011)
Phase III Randomized, Placebo(Pl)-Controlled, Double-Blind Study of Intravenous Calcium/Magnesium (CaMg) to Prevent Oxaliplatin-Induced Sensory Neurotoxicity (sNT), N08CB: an Alliance for Clinical Trials in Oncology Study1
Authors: Axel Grothey, Rui Qin, Shaker Dakhil, Louis Fehrenbacher, Philip Stella, Pamela Atherton, Drew Seisler, Rubin Qamar, Grant Lewis, Charles Loprinzi
Journal: Annals of Oncology (2013)
Guidelines of care for superficial mycotic infections of the skin: Piedra
Authors: None Guidelines/Outcomes Committee, Lynn A Drake, Scott M Dinehart, Evan R Farmer, Robert W Goltz, Gloria F Graham, Maria K Hordinsky, Charles W Lewis, David M Pariser, John W Skouge, Stephen B Webster, Duane C Whitaker, Barbara Butler, Barbara J Lowery, None Task Force, Boni E Elewski, Mervyn L Elgart, Paul H Jacobs, Jack L Lesher, Richard K Scher
Journal: Journal of the American Academy of Dermatology (1996)
Surfactant inhibition by plasma proteins: differential sensitivity of various surfactant preparations
Authors: W Seeger, C Grube, A Günther, R Schmidt
Journal: European Respiratory Journal (1993)

Leakage of plasma proteins into the alveolar space may inhibit surfactant function. We compared the surface properties and the sensitivity to inhibitory proteins of different organic solvent surfactant extracts and a synthetic surfactant. Experiments were performed in the pulsating bubble surfactometer, with surfactant concentrations ranging between 0.1 and 2 mg.ml-1. Inhibition profiles towards fibrinogen, albumin and haemoglobin were obtained from calf lung surfactant extracts (CLSE), Alveofact, Curosurf and Survanta (all used in clinical, replacement studies in respiratory distress syndrome (RDS) and of an apoprotein-based synthetic phospholipid mixture (PLM-C/B; DPPC:PG:PA = 68.5:22.5:9, supplemented with 2% wt/wt non-palmitoylated human recombinant SP-C and 1% t/wt natural bovine SP-B). In the absence of inhibitory proteins, all surfactants exhibited dose-dependent rapid adsorption (rank order of relative efficacy PLM-C/B = CLSE > Alveofact > Curosurf > Survanta). Minimal surface tension was reduced to near zero values under dynamic compression (rank order PLM-C/B > CLSE > Alveofact = Curosurf) and to approximately 4 mN.m-1 (Survanta). Curosurf and Survanta were dose-dependently inhibited by fibrinogen > haemoglobin > albumin, with far-reaching loss of surface activity at protein-surfactant ratios above 1:1. In contrast, CLSE and Alveofact were only moderately inhibited by fibrinogen, and were not affected by haemoglobin and albumin, up to protein-surfactant ratios of 2:1. PLM-C/B exhibited resistance to fibrinogen, intermediate sensitivity to albumin, and was severely inhibited by haemoglobin. We conclude that various natural surfactant extracts and an apoprotein-based synthetic surfactant mixture markedly differ in their sensitivity to inhibitory plasma proteins.(ABSTRACT TRUNCATED AT 250 WORDS)
Phase II, Randomized, Double-Blind Study of Two Dose Levels of Arzoxifene in Patients With Locally Advanced or Metastatic Breast Cancer
Authors: Aman Buzdar, Joyce A. O’Shaughnessy, Daniel J. Booser, John E. Pippen, Stephen E. Jones, Pamela N. Munster, Patrick Peterson, Allen S. Melemed, Eric Winer, Clifford Hudis
Journal: Journal of Clinical Oncology (2003)

To select a daily dose of arzoxifene (LY353381), a selective estrogen receptor modulator, for use in future studies in women with locally advanced or metastatic breast cancer who are either potentially tamoxifen sensitive (TS) or tamoxifen refractory (TR).This trial was a randomized, double-blind, phase II study of arzoxifene 20 mg (n = 55) and 50 mg (n = 57) in women with advanced or metastatic breast cancer. Patients were randomly assigned to balance for number of metastatic disease sites, prior tamoxifen therapy, and estrogen receptor status. The primary end point was tumor response rate (RR). Secondary end points included clinical benefit rate (CBR), time to progression (TTP), and toxicity.Forty-nine patients were TS and 63 were TR. According to independent review, among TS patients, RR was higher in the 20-mg arm than the 50-mg arm (26.1% v 8.0%), with a longer TTP (8.3 v 3.2 months; P >.05). Among the TR patients, response rate was the same in the 20-mg and 50-mg arms (10.3%) with similar TTP (2.7 and 2.8 months, respectively; P >.05). CBR was higher in the 20-mg arm than in the 50-mg arm among TS patients (39.1% v 20.0%) and TR patients (13.8% v 10.3%). Arzoxifene was well tolerated. Dose-dependent toxicity was not demonstrated. There were no deaths during study.Arzoxifene is effective in the treatment of TS and TR patients with advanced or metastatic breast cancer at the 20-mg and 50-mg dose levels. Toxicities are minimal, and the therapy is tolerated. The 20-mg dose seems to be at least as effective as the 50-mg dose. Accordingly, arzoxifene 20 mg/d was selected for further study in patients with breast cancer.
LONG-TERM THERAPY WITH ROSUVASTATIN DECREASES EXPRESSION OF HYPERTROPHIC AND PRO-INFLAMMATORY PROTEINS IN LEFT VENTRICULAR MYOCARDIUM OF DOGS WITH MODERATE HEART FAILURE
Authors: Sudhish Mishra, Sharad Rastogi, Michael S. Sabbah, Ramesh C. Gupta, Kaitlin Dye, Andrew Cavanagh, Hani N. Sabbah
Journal: Journal of the American College of Cardiology (2010)