tbuckley/cabot-search huggingface dataset:
An Effect-Size Analysis of the Relative Efficacy and Tolerability of Serotonin Selective Reuptake Inhibitors for Panic Disorder
Authors: Michael W. Otto, Kimberly S. Tuby, Robert A. Gould, Renée Y.S. McLean, Mark H. Pollack
Journal: American Journal of Psychiatry (2001)

Serotonin selective reuptake inhibitors (SSRIs) are now considered the first-line pharmacotherapy for panic disorder. The preferential use and the presumption of greater tolerability of SSRIs relative to older agents, such as tricyclic antidepressants, occurred without direct comparisons between the two classes of medication. In this study the authors used an effect-size analysis to provide an initial comparison.The authors conducted an effect-size analysis of 12 placebo-controlled, efficacy trials of SSRIs for panic disorder and compared these results to findings obtained in a recent meta-analysis of non-SSRI treatments for panic disorder.The mean effect size for acute treatment outcome for SSRIs relative to placebo was 0.55, not significantly different from that for antidepressants in general (0.55) and for imipramine in particular (0.48). More recent studies of SSRIs, and studies using larger samples, were associated with lower effect sizes. No significant differences were found in dropout rates between those taking SSRIs and those taking older agents during acute treatment.An effect-size analysis of controlled studies of treatments for panic disorder revealed no significant differences between SSRIs and older antidepressants in terms of efficacy or tolerability in short-term trials. An inverse relationship was evident between sample size and effect size for SSRIs. Early studies of small samples may have led to initial overestimations of the efficacy of SSRIs for panic disorder.
Angiographic and Clinical Outcomes in Patients Receiving Low-Molecular-Weight Heparin Versus Unfractionated Heparin in ST-Elevation Myocardial Infarction Treated With Fibrinolytics in the CLARITY-TIMI 28 Trial
Authors: Marc S. Sabatine, David A. Morrow, Gilles Montalescot, Mikael Dellborg, Jose L. Leiva-Pons, Matyas Keltai, Sabina A. Murphy, Carolyn H. McCabe, C. Michael Gibson, Christopher P. Cannon, Elliott M. Antman, Eugene Braunwald
Journal: Circulation (2005)

Low-molecular-weight heparin (LMWH) offers pharmacological and practical advantages over unfractionated heparin (UFH). Whether these advantages translate into greater infarct-related artery patency and fewer adverse clinical events in patients with ST-elevation myocardial infarction (STEMI) receiving fibrinolytic therapy remains under study.We compared angiographic and clinical outcomes in patients treated with LMWH (n=1429) versus UFH (n=1431) in CLARITY-TIMI 28, a randomized trial of clopidogrel versus placebo in STEMI patients aged 18 to 75 years undergoing fibrinolysis. After comprehensive adjustment for baseline characteristics, therapeutic interventions, and a propensity score, treatment with LMWH was associated with a significantly lower rate of a closed infarct-related artery or death or myocardial infarction before angiography (13.5% versus 22.5%, adjusted OR 0.76, P=0.027). Treatment with LMWH was also associated with a significantly lower rate of cardiovascular death or recurrent myocardial infarction through 30 days (6.9% versus 11.5%, adjusted OR 0.68, P=0.030). The lower event rates were observed in patients allocated to clopidogrel and in those who underwent percutaneous coronary intervention. Rates of TIMI major bleeding through 30 days (1.6% versus 2.2%, P=0.27) and intracranial hemorrhage (0.6% versus 0.8%, P=0.37) were similar in the LMWH and UFH groups. Patients who received both clopidogrel and LMWH, in addition to a standard fibrinolytic and aspirin, had a particularly high rate of infarct-related artery patency (90.9%) and particularly low rates of cardiovascular death (3.2%), recurrent myocardial infarction (3.0%), and major bleeding (1.8%).In patients with STEMI receiving fibrinolytic therapy, use of LMWH with other standard therapies, including clopidogrel and aspirin, is associated with improved angiographic outcomes and lower rates of major adverse cardiovascular events.
Effect of respiratory syncytial virus on subsequent allergic sensitization to ovalbumin in guinea‐pigs
Authors: A. Dakhama, A.m Bramley, N.g Chan, K.o McKay, R.r Schellenberg, R.g Hegele
Journal: European Respiratory Journal (1999)

Children with acute respiratory syncytial virus (RSV) bronchiolitis often develop recurrent wheezing, asthma and allergic sensitization, but the role of RSV in the pathogenesis of these sequelae is unclear. This study examined whether RSV infection potentiates subsequent allergic sensitization, airway hyperresponsiveness (AHR) and airway inflammation induced by repeated exposures to aerosolized ovalbumin (OA) in guinea-pigs. Guinea-pigs received either RSV or sham inoculum, followed by exposures to OA- or saline-containing aerosols to form the following groups: 1) noninfected, nonsensitized controls (sham/saline group); 2) RSV-infected, nonsensitized animals (RSV/ saline group); 3) noninfected, OA-sensitized animals (sham/OA group); 4) RSV infection and first OA exposure on the same day (RSV/OA group), and 5) RSV infection six days prior to first OA exposure (RSV6/OA group). Three days after the final aerosol exposure, circulating OA-specific immunoglobulin (Ig)G1 antibody titres and AHR to inhalation acetylcholine challenge were measured and morphometry performed to evaluate allergic inflammation of the airways. OA-exposed animals developed OA-specific IgG1 antibodies, AHR and airway eosinophilia (sham/OA, RSV/OA and RSV6/OA groups. RSV infection alone induced significant AHR and airway eosinophilia (RSV/saline group). RSV infection, and concomitant exposure to OA (RSV/OA group) enhanced OA-specific IgG1 antibodies, but not airway eosinophilia or AHR. Such increases were not observed in the RSV6/OA group. In conclusion, respiratory syncytial virus potentiates the production of ovalbumin-specific immunoglobulin G1 antibodies in guinea-pigs, but circulating titres of these antibodies do not reflect the extent of airway hyperresponsiveness or airway inflammation. In addition, respiratory syncytial virus infection alone can produce slight increases in airway hyperresponsiveness that are associated with increased numbers of eosinophils in the airways.
The partition matrix: exploring variable phylogenetic signals along nucleotide sequence alignments
Authors: I. B. Jakobsen, S. R. Wilson, S. Easteal
Journal: Molecular Biology and Evolution (1997)

The partition matrix is a graphical tool for comparative analysis of nucleotide sequences following alignment. It is particularly useful for investigating the divergent phylogenies of sequence regions undergoing reticulate evolution. A partition matrix is generated by determining the consistency of the parsimoniously informative sites in a set of aligned sequences with the binary partitions inferred from the sequences. Since the linear order of sites is maintained, the matrix can be used to assess whether the distribution of sites either supporting or conflicting with particular partitions changes along the length of the alignment. The usefulness of the matrix in allowing visual identification of differences in evolutionary history among regions depends on the order in which partitions are shown; several suitable ordering schemes are proposed. We demonstrate the use of the partition matrix in interpreting the evolution of the pseudoautosomal boundary region on the sex chromosome of catarrhine primates. Its routine use should help to avoid attempts to derive single phylogenies from sequences whose evolution has been reticulate and to identify the gene conversion or recombination events underlying the reticulation. The method is relatively fast. It is exploratory, and it can form the basis for more formal analysis, which we discuss.
A Randomised Phase 2 Trial of Dexamethasone Versus Prednisolone in Castration-resistant Prostate Cancer
Authors: Ramachandran Venkitaraman, David Lorente, Vedang Murthy, Karen Thomas, Lydia Parker, Ruth Ahiabor, David Dearnaley, Robert Huddart, Johann De Bono, Chris Parker
Journal: European Urology (2014)
Direct Assessment of Coronary Steal and Associated Changes of Collateral Hemodynamics in Chronic Total Coronary Occlusions
Authors: Gerald S. Werner, Hans R. Figulla
Journal: Circulation (2002)

Background — Coronary steal can occur in collateral-dependent myocardium during pharmacologically induced vasodilation. This study assessed coronary steal invasively in chronic total coronary occlusions (TCOs). Methods and Results — In 35 consecutive patients with a percutaneous transluminal coronary angioplasty of a TCO (duration &gt;4 weeks), coronary flow velocity (APV) by a Doppler wire and distal pressure (P D ) by a pressure wire were assessed in the collateral-dependent vascular bed before dilatation. Indexes of peripheral resistance (R P ) and for the collateral pathway, including the donor artery segment (R CP ), were calculated. Changes of these parameters were assessed during intravenous adenosine (140 μg · kg −1 · min −1 ). Adenosine caused a decrease of APV, ie, coronary steal, in 13 patients (37%; group S), an increase in 11 patients (group R), and no change in 11 patients (group N). Angiographic analysis of collateral pathways showed no difference between the groups, except that in group S all collateral connections were continuously visible but no large collaterals (&gt;0.5 mm) were found. In group N, collaterals were least developed. The increase of APV in group R was associated with a decrease of R P , whereas R CP remained unchanged. In contrast, group S showed no change in R P but a significant increase of R CP , indicating an increased resistance of the donor segment. Conclusions — Coronary steal is observed in about one third of TCOs and is associated with specific hemodynamic changes of R P and R CP . Steal occurred only with well-developed angiographically visible collaterals but not with very large collaterals.
Metabolically Healthy but Obese Women Have an Intermediate Cardiovascular Risk Profile Between Healthy Nonobese Women and Obese Insulin-Resistant Women
Authors: Maria Adelaide Marini, Elena Succurro, Simona Frontoni, Marta Letizia Hribal, Francesco Andreozzi, Renato Lauro, Francesco Perticone, Giorgio Sesti
Journal: Diabetes Care (2007)

Obesity is associated with metabolic and cardiovascular risk factors that include type 2 diabetes, hypertension, and dyslipidemia (1–4). A subset of obese subjects has been identified that appears to be protected from obesity-related metabolic abnormalities (5–11). These subjects, termed metabolically healthy but obese (MHO), are relatively insulin sensitive and have a rather favorable cardiovascular risk profile (5–11). Although the existence of MHO individuals has been recognized, only a few studies have examined in detail the metabolic characteristics associated with their protective profile (5–13). Whereas MHO individuals appear to have a more favorable cardiovascular risk profile than insulin-resistant obese (IRO) individuals, they show early signs of atherosclerosis compared with lean subjects, which could not be explained by alterations in cardiovascular risk factors (12). Among the factors that may account for the early atherosclerosis, insulin-like growth factor (IGF)-1 is a plausible candidate because low plasma IGF-1 concentrations are associated with type 2 diabetes, insulin resistance (14–16), and increased risk of coronary artery disease (17–22). To further characterize the protective profile of MHO individuals, we compared clinical characteristics, including cardiovascular risk factors, plasma IGF-1 levels, and intima-media thickness (IMT) of the common carotid artery, of a group of MHO women from a cohort of nondiabetic Italian Caucasians with those of two age-matched groups comprising healthy nonobese or …
Gene Expression Profiling of Primary Cutaneous Melanoma and Clinical Outcome
Authors: Véronique Winnepenninckx, Vladimir Lazar, Stefan Michiels, Philippe Dessen, Marguerite Stas, Soledad R. Alonso, Marie-Françoise Avril, Pablo L. Ortiz Romero, Thomas Robert, Ovidiu Balacescu, Alexander M. M. Eggermont, Gilbert Lenoir, Alain Sarasin, Thomas Tursz, Joost J. van den Oord, Alain Spatz
Journal: JNCI Journal of the National Cancer Institute (2006)

Gene expression profiling data for human primary cutaneous melanomas are scarce because of the lack of retrospective collections of frozen tumors. To identify differentially expressed genes that may be involved in melanoma progression and prognosis, we investigated the relationship between gene expression profiles and clinical outcome in a cohort of patients with primary melanoma.Labeled complementary RNA (cRNA) from each tissue sample was hybridized to a pangenomic 44K 60-mer oligonucleotide microarray. Class comparison and class prediction analyses were performed to identify genes whose expression in primary melanomas was associated with 4-year distant metastasis-free survival among 58 patients with at least 4 years of follow-up, distant metastasis, or death. Results were validated immunohistochemically at the protein level in 176 independent primary melanomas from patients with a median clinical follow-up of 8.5 years. Survival was analyzed with a Cox multivariable model and stratified log-rank test. All statistical tests were two-sided.We identified 254 genes that were associated with distant metastasis-free survival of patients with primary melanoma. These 254 genes include genes involved in activating DNA replication origins, such as minichromosome maintenance genes and geminin. Twenty-three of these genes were studied at the protein level; expression of five (MCM4, P = .002; MCM3, P = .030; MCM6, P = .004; KPNA2, P = .021; and geminin, P = .004) was statistically significantly associated with overall survival in the validation set. In a multivariable Cox model adjusted for tumor thickness, ulceration, age, and sex, expression of MCM4 (hazard ratio [HR] of death = 4.04, 95% confidence interval [CI] = 1.39 to 11.76; P = .010) and MCM6 (HR of death = 7.42, 95% CI = 1.99 to 27.64; P = .003) proteins was still statistically significantly associated with overall survival.We identified 254 genes whose expression was associated with metastatic dissemination of cutaneous melanomas. These genes may shed light on the molecular mechanisms underlying poor prognosis in melanoma patients.
Short-term effects of particulate air pollution on respiratory morbidity in asthmatic children
Authors: A Peters, DW Dockery, J Heinrich, HE Wichmann
Journal: European Respiratory Journal (1997)

Short-term effects of air pollution (consisting primarily of sulphur dioxide and particulate matter but with low acidity) on respiratory morbidity were studied in asthmatic children from Sokolov, Czech Republic. Eighty nine children with asthma, who recorded daily peak expiratory flow measurements, symptoms and medication use in a diary, were analysed for 7 months during the winter of 1991-1992. Air pollution measurements included: SO2, total suspended particulates (TSPs), inhalable particles, ie. particulate matter of aerodynamic diameter < or = 10 microm, particle strong acidity (PSA) and fine particle sulphate concentration (SO4). Linear and logistic regression analyses estimated the impact of air pollutants adjusted for trend, temperature and weekend and autocorrelated errors. Exposure to elevated levels of air pollution was associated with decreased peak expiratory flow rates, increased respiratory symptoms, increased prevalence of school absence and fever, and increased medication use. Prolonged exposure to particle SO4 showed the largest effect estimates. At the end of January, an air pollution episode occurred, during which respiratory symptoms, prevalence of fever, school absence and asthma medication increased. The association between respiratory symptoms and particulate SO4 was highly dependent on this episode, whilst the associations between lung function and SO4 as well as between fever and SO4 were still observed when this air pollution episode was excluded. Some evidence was found that exposure to air pollution might have enhanced the respiratory symptoms while children were experiencing respiratory infections. In this study, a panel of children with mild asthma experienced small decreases in peak expiratory flow and increased dyspnoea in association with fine particles formed during air pollution episodes.
Setting a research agenda for medical overuse
Authors: Daniel J Morgan, Shannon Brownlee, Aaron L Leppin, Nancy Kressin, Sanket S Dhruva, Les Levin, Bruce E Landon, Mark A Zezza, Harald Schmidt, Vikas Saini, Adam G Elshaug
Journal: BMJ (2015)

Although overuse in medicine is gaining increased attention, many questions remain unanswered. <b>Dan Morgan and colleagues </b>propose an agenda for coordinated research to improve our understanding of the problem
THE INACTIVATION OF COMPLEMENT AND ITS COMPONENTS BY PLASMIN
Authors: Louis Pillemer, Oscar D. Ratnoff, Livia Blum, I. H. Lepow
Journal: The Journal of Experimental Medicine (1953)

Human complement is inactivated by plasmin, the proteolytic enzyme of plasma or serum active at or near neutrality. The addition of streptokinase to human serum, which converts plasminogen to plasmin, also causes the inactivation of complement components C'2 and C'4 and varying amounts of C'1. C'3 is the most resistant to inactivation by plasmin. Chloroform-activated human plasmin and bovine plasmin also destroy these components of complement, but are less effective than the streptokinase-activated enzyme. The inactivation of complement by the addition of streptokinase to human serum is inhibited by high hydrogen ion concentrations, low temperature, and elevated ionic strength. The inactivation of the components of complement in various fractions of serum is influenced by the available plasminogen and the content of plasmin inhibitors in these fractions. Certain similarities are pointed out between the components of complement and the factors in the plasmin system and between the inactivation of the components of complement by antigen-antibody reactions, by specific agents, and by plasmin. The possible significance of these relationships in immune hemolysis and complement fixation, and the possible role of the plasmin system in the instability of complement and the development of anticomplementary properties in serum are discussed.
Acquired factor V deficiency in a patient with pulmonary tuberculosis
Authors: JL Aliaga, J de Gracia, R Vidal, M Pico, P Flores, G Sampol
Journal: European Respiratory Journal (1990)

A 29 yr old man with pulmonary tuberculosis and concomitant acquired plasma coagulation factor V deficiency is reported. The case is discussed together with three previously described cases. The bleeding tendency in a patient with pulmonary tuberculosis may be caused by a coagulation factor antibody and may be corrected by chemotherapy, as in the case described. Special therapeutic approaches are required in some cases.
The Effect of Posture on Diaphragmatic Movement and Vital Capacity in Normal Subjects
Authors: O. L. Wade, J. C. Gilson
Journal: Thorax (1951)

Since earliest times the diaphragm has attracted attention from philosophers as well as anatomists and physiologists.Hailer (1738) summarized the opinion of the Renaissance anatomists when he described the diaphragm as nobilissimus post cor musculus.Buffon, quoted by Bell (1826), reiterated a medieval superstition by describing its central tendon as a nervous centre, the place of all emotions and the seat of the soul: " in sickness and oppression, lowness and sighing, weeping and laughing, in joy or in fear, all our feelings seem to concentrate in this part."At the beginning of the nineteenth century Bell (1826) and Astley Cooper (1839) demonstrated that life could be maintained by diaphragmatic breathing alone after injuries to the cervical spinal cord in man.Duchenne (1867) used the newly dis- covered faradic current to investigate the action of the diaphragm in respiration of men and animals.He stimulated the phrenic nerve in dogs, horses, and men, and found it caused the diaphragm to descend and the costal margin to rise upwards and outwards.In dead animals he made similar observations, but when he had opened the anterior abdominal wall and removed the viscera he found phrenic stimulation caused the diaphragm to descend, drawing the costal margin inwards and downwards.He believed that in life the diaphragm in its descent lifted the lower edge of the costal margin upwards and outwards by leverage against the abdominal viscera.Although the mode of action of the diaphragn was the subject of controversy among physiologists (Magendie, 1825; Duchenne, 1867; Bert, 1870), it was accepted that the diaphragm was the most important muscle of respiration.EARLY RADIOLOGICAL OBSERVATIONS AND MEASUREMENTS OF DIAPHRAGMATIC MOVEMENTS The introduction of radiology awakened great interest in the mechanics of respira- tion, and Keith (1909) expressed the view of most observers of the time that there H on July 16, 2023 by guest.
Human B cell activation. Evidence for diverse signals provided by various monoclonal anti-IgM antibodies.
Authors: S M Rudich, R Winchester, P K Mongini
Journal: The Journal of Experimental Medicine (1985)

Seven murine monoclonal antibodies (mAb) with different binding characteristics for human IgM varied markedly in their ability to induce proliferation of T cell-depleted human splenocytes. Two mAb (HB57 and 5D7) that bound to distinct epitopes on IgM were highly effective initiators of B cell proliferation at very low concentrations, in the presence of a T cell factor source. In the absence of T cell supernatant, both HB57 and 5D7 mAbs produced a markedly reduced degree of stimulation at all concentrations. Two additional anti-IgM mAb (VIIIE11 and Mu53) were distinctive in that, even at high concentrations, only limited proliferation was observed compared with the first group of mAb. This proliferation depended on the presence of T cell supernatant. Competitive-binding studies revealed that the epitope recognized by mAb Mu53 may be identical or very proximate to that recognized by HB57. Three other mAb (1G6, XG9, and P24) induced little or no proliferation. 1G6 bound to a unique epitope on the IgM molecule, whereas XG9 shared a determinant with VIIIE11 mAb. Regulatory influences of Fc receptor binding cannot account for all the diversity in proliferation observed with the individual anti-IgM mAb. Markedly augmented proliferation was obtained when B cells were cultured with certain combinations of anti-IgM mAb in the presence of exogenous T cell supernatant. The proliferation induced in the absence of T cell supernatant by high concentrations of mAb mixtures that included 1G6 approached that observed for the same mixtures in the presence of T cell supernatant. The data suggest that certain signals delivered through membrane IgM can bypass the need for T cell supernatant in the activation of human B lymphocytes.