tbuckley/cabot-search huggingface dataset:
Validity of indirect comparison for estimating efficacy of competing interventions: empirical evidence from published meta-analyses
Authors: F. Song
Journal: BMJ (2003)

<h3>Abstract</h3> <b>Objective:</b> To determine the validity of adjusted indirect comparisons by using data from published meta-analyses of randomised trials. <b>Design:</b> Direct comparison of different interventions in randomised trials and adjusted indirect comparison in which two interventions were compared through their relative effect versus a common comparator. The discrepancy between the direct and adjusted indirect comparison was measured by the difference between the two estimates. <b>Data sources:</b> Database of abstracts of reviews of effectiveness (1994-8), the Cochrane database of systematic reviews, Medline, and references of retrieved articles. <b>Results:</b> 44 published meta-analyses (from 28 systematic reviews) provided sufficient data. In most cases, results of adjusted indirect comparisons were not significantly different from those of direct comparisons. A significant discrepancy (P&lt;0.05) was observed in three of the 44 comparisons between the direct and the adjusted indirect estimates. There was a moderate agreement between the statistical conclusions from the direct and adjusted indirect comparisons (κ 0.51). The direction of discrepancy between the two estimates was inconsistent. <b>Conclusions:</b> Adjusted indirect comparisons usually but not always agree with the results of head to head randomised trials. When there is no or insufficient direct evidence from randomised trials, the adjusted indirect comparison may provide useful or supplementary information on the relative efficacy of competing interventions. The validity of the adjusted indirect comparisons depends on the internal validity and similarity of the included trials. <h3>What is already known on this topic</h3> Many competing interventions have not been compared in randomised trials Indirect comparison of competing interventions has been carried out in systematic reviews, often implicitly Indirect comparison adjusted by a common control can partially take account of prognostic characteristics of patients in different trials <h3>What this study adds</h3> Results of adjusted indirect comparison usually, but not always, agree with those of head to head randomised trials The validity of adjusted indirect comparisons depends on the internal validity and similarity of the trials involved
Thromboembolic Adverse Events After Use of Recombinant Human Coagulation Factor VIIa
Authors: Kathryn A. O’Connell
Journal: JAMA (2006)

The US Food and Drug Administration (FDA) licensed recombinant human coagulation factor VIIa (rFVIIa) on March 25, 1999, for bleeding in patients with hemophilia A or B and inhibitors to factors VIII or IX. Use in patients without hemophilia has been increasing since licensure.To review serious thromboembolic adverse events (AEs) reported to the FDA's Adverse Event Reporting System (AERS).The AERS database was reviewed from March 25, 1999, through December 31, 2004, for thromboembolic AE reports with rFVIIa. The AERS database includes US and non-US spontaneous AE reports from both approved (specific indications for patients with hemophilia) and unlabeled uses. It also includes serious AEs in patients enrolled in postlicensure clinical trials who received rFVIIa. Manufacturer reporting to FDA is mandatory, but primary notification from clinicians and others to FDA or manufacturers is voluntary for spontaneous reports; therefore, AERS underrepresents actual event occurrences.Reported thromboembolic events occurring in patients administered rFVIIa.A total of 431 AE reports for rFVIIa were found, of which 168 reports described 185 thromboembolic events. Seventeen events occurred in patients with hemophilia and 59 occurred in patients enrolled in postlicensure trials. Unlabeled indications accounted for 151 of the reports, most with active bleeding (n = 115). Reported AEs were thromboembolic cerebrovascular accident (n = 39), acute myocardial infarction (n = 34), other arterial thromboses (n = 26), pulmonary embolism (n = 32), other venous thromboses (including deep vein thrombosis) (n = 42), and clotted devices (n = 10). In 36 (72%) of 50 reported deaths, the probable cause of death was the thromboembolic event. In 144 patients with timing information, 73 events (52%) occurred in the first 24 hours after the last dose (30 events within 2 hours). Sixty-four reports (38%) noted concomitant use of hemostatic agents. Most reports lacked sufficient information to evaluate potential dosage associations.Most reported thromboembolic AEs followed the use of rFVIIa for unlabeled indications and occurred in arterial and venous systems, often resulting in serious morbidity and mortality. Analysis of the relationship between AEs and rFVIIa is hindered by concomitant medications, preexisting medical conditions, confounding by indication, and inherent limitations of passive surveillance. Randomized controlled trials are needed to establish the safety and efficacy of rFVIIa in patients without hemophilia.
Perinatal Outcomes in Pregnant Women Exposed to Omalizumab: Interim Results from a Prospective, Observational Study
Authors: Jennifer A. Namazy, Abdelkader Rahmaoui, Michael D. Cabana, Angela E. Scheuerle, John M. Thorp, Gillis Carrigan, Elizabeth B. Andrews
Journal: Journal of Allergy and Clinical Immunology (2015)
Mutations in AP2S1 cause familial hypocalciuric hypercalcemia type 3
Authors: M Andrew Nesbit, Fadil M Hannan, Sarah A Howles, Anita A C Reed, Treena Cranston, Clare E Thakker, Lorna Gregory, Andrew J Rimmer, Nigel Rust, Una Graham, Patrick J Morrison, Steven J Hunter, Michael P Whyte, Gil McVean, David Buck, Rajesh V Thakker
Journal: Nature Genetics (2012)
Lack of functional and expression homology between human and mouse aldo-keto reductase 1C enzymes: implications for modelling human cancers
Authors: Pedro Veliça, Nicholas J Davies, Pedro P Rocha, Heinrich Schrewe, Jonathan P Ride, Chris M Bunce
Journal: Molecular Cancer (2009)

Abstract Background Over recent years, enzymes of the aldo-keto reductase (AKR) 1C subfamily have been implicated in the progression of prostate, breast, endometrial and leukemic cancers. This is due to the ability of AKR1C enzymes to modify androgens, estrogens, progesterone and prostaglandins (PGs) in a tissue-specific manner, regulating the activity of nuclear receptors and other downstream effects. Evidence supporting a role for AKR1C enzymes in cancer derives mostly from studies with isolated primary cells from patients or immortalized cell lines. Mice are ideal organisms for in vivo studies, using knock-out or over-expression strains. However, the functional conservation of AKR1C enzymes between human and mice has yet to be described. Results In this study, we have characterized and compared the four human (AKR1C1,-1C2, -1C3 and -1C4) and the eight murine (AKR1C6, -1C12, -1C13, -1C14, -1C18, -1C19, -1C20 and -1C21) isoforms in their phylogeny, substrate preference and tissue distribution. We have found divergent evolution between human and murine AKR1C enzymes that was reflected by differing substrate preference. Murine enzymes did not perform the 11β-ketoreduction of prostaglandin (PG) D 2 , an activity specific to human AKR1C3 and important in promoting leukemic cell survival. Instead, murine AKR1C6 was able to perform the 9-ketoreduction of PGE 2 , an activity absent amongst human isoforms. Nevertheless, reduction of the key steroids androstenedione, 5α-dihydrotestosterone, progesterone and estrone was found in murine isoforms. However, unlike humans, no AKR1C isoforms were detected in murine prostate, testes, uterus and haemopoietic progenitors. Conclusions This study exposes significant lack of phylogenetic and functional homology between human and murine AKR1C enzymes. Therefore, we conclude that mice are not suitable to model the role of AKR1C in human cancers and leukemia.
The innate schema of natural numbers does not explain historical, cultural, and developmental differences
Authors: Marie-Pascale Noël, Jacques Grégoire, Gaëlle Meert, Xavier Seron
Journal: Behavioral and Brain Sciences (2008)

Abstract Rips et al.'s proposition cannot account for the facts that (1) a historical look at the word number systems suggests that the concept of natural numbers has been progressively elaborated; (2) people from cultures without an elaborate counting system do not master the concept of natural numbers; (3) children take time to master natural numbers; and (4) the competing advantage of the postulated math schema in the natural selection process is not obvious.
Estrogens Inhibit Angiotensin II–Induced Leukocyte–Endothelial Cell Interactions In Vivo via Rapid Endothelial Nitric Oxide Synthase and Cyclooxygenase Activation
Authors: Ángeles Álvarez, Carlos Hermenegildo, Andrew C. Issekutz, Juan V. Esplugues, Maria-Jesus Sanz
Journal: Circulation Research (2002)

Angiotensin II (Ang II) may be a key molecule in the development of atherosclerosis. Because the incidence of coronary atherosclerosis in premenopausal women is lower than that observed in men or postmenopausal women, we have investigated the effect of estrogens on Ang II–induced leukocyte recruitment in vivo using intravital microscopy in the rat mesenteric microcirculation. Superfusion for 60 minutes with Ang II induced a significant increase in leukocyte rolling flux, adhesion, and emigration. Administration of 17-β-estradiol (17-β-E) after 30 minutes of Ang II superfusion produced a reduction of these leukocyte responses by 55.1%, 72.7%, and 70.9%, respectively, an additional 30 minutes later. The effect observed with 17-β-E was receptor-mediated and specific. 17-β-E superfusion did not modify either L-NAME or indomethacin-induced leukocyte responses. Inhibitory responses caused by 17-β-E were not altered by either 7-nitroindazole or actinomycin D cosuperfusion. Stimulation of endothelial cells with 17-β-E caused a rapid and dose-dependent release of prostacyclin. Finally, tamoxifen or ICI 182,780 administration provoked a significant increase in leukocyte–endothelial cell interactions 90 minutes later, which were significantly attenuated by systemic preadministration with an Ang II AT 1 receptor antagonist. Tamoxifen-induced leukocyte responses were also reduced by systemic pretreatment with an anti–P-selectin mAb and an anti–CD18 mAb. Hence, the antiatherogenic effects of estrogens may be mediated by inhibition of Ang II–induced leukocyte recruitment through endothelial NO and prostacyclin release. Furthermore, scarcity of estrogens resulted in decreased levels of vasodilators and the exposure of the endothelium to the deleterious action of Ang II, which may explain the higher incidence of coronary atherosclerosis in men and postmenopausal women.
Involvement of the <i>RASSF1A</i> Tumor Suppressor Gene in Controlling Cell Migration
Authors: Ashraf Dallol, Angelo Agathanggelou, Stella Tommasi, Gerd P. Pfeifer, Eamonn R. Maher, Farida Latif
Journal: Cancer Research (2005)

We have previously shown that RASSF1A associates with the microtubules. This association alters the microtubule dynamics and seems essential for RASSF1A tumor suppressive function. Mutant variants of RASSF1A that do not associate fully with the microtubules have reduced ability to stabilize them and cause cell cycle arrest. Here we show that overexpression of RASSF1A diminished the ability of A549 non-small cell lung cancer cells to migrate either through a transwell filter or to close a wound. In addition, we employed gene knockdown as well as mouse embryonic fibroblasts (MEFs) from Rassf1a knockout mice to analyze RASSF1A function in controlling cell motility. A549 cells stably transfected with RASSF1A exhibited increased cell-cell adhesion and less refractive morphology compared with controls. Conversely, RASSF1A knockdown in HeLa caused loss of cell-cell adhesion and a more refractive morphology. RASSF1A-depleted HeLa cells as well as Rassf1a-/- MEFs displayed increased cell migration that could be partly phosphatidylinositol 3-kinase dependent. Time-lapse microscopy showed the RASSF1A-depleted cells are highly motile with fibroblast-like morphology and diminished cell-cell adhesion. Staining of the cytoskeleton in RASSF1A-depleted HeLa cells and MEFs show marked differences in terms of microtubules outgrowth and actin stress fibers formation. This observation was associated with increased activation of Rac1 in RASSF1A-knockdown cells and the Rassf1a-/- MEFs. In addition, expression of a dominant-negative variant of Rac1 in the RASSF1A-depleted HeLa cells reduced their ability to form lamellipodia and other protrusions. These findings represent a novel function for RASSF1A, which may help explain its tumor suppression ability independently of its effects on cell cycle and apoptosis.
Perception of respiratory symptoms after methacholine-induced bronchoconstriction in a general population
Authors: G Devereux, DJ Hendrick, SC Stenton
Journal: European Respiratory Journal (1998)

In an epidemiological study, methacholine-induced bronchoconstriction was used as a physical illustration of the sensations associated with asthma. The objective of this study was to assess whether familiarity with these sensations could be used as a measure of asthma prevalence. Eight hundred and seventy six subjects aged 20-44 yrs completed a respiratory questionnaire and a measurement of airway responsiveness (the provocative dose of methacholine causing a 20% fall in forced expiratory volume in one second (PD20)). Subjects were asked about their perception of, familiarity with and description of the respiratory sensations experienced at the time of maximal bronchoconstriction. The questionnaire-derived lifetime prevalences of wheeze, chest tightness and undue breathlessness were 43, 35 and 22% respectively. Asthma medication was used by 8% and the lifetime prevalence of diagnosed asthma was 12%. Quantifiable levels of airway responsiveness were measured in 34%, and airway responsiveness in the range considered to be consistent with untreated active asthma was present in 21%. Bronchoconstriction was perceived by 59%. Perception of bronchoconstriction was associated with the magnitude of bronchoconstriction, younger age, female sex and questionnaire-reported symptoms. Of subjects able to perceive bronchoconstriction, 58% reported previous experience of (familiarity with) the associated respiratory sensations. Familiarity with the sensations of bronchoconstriction was associated with questionnaire-reported symptoms, diagnosed asthma and increasing levels of airway responsiveness. There was poor agreement between the respiratory symptoms reported by questionnaire before the methacholine test and the words used to describe respiratory sensations induced by the test. Familiarity with the sensations of methacholine-induced bronchoconstriction has all the appropriate associations of a measure of asthma prevalence and may be a useful adjunct to symptom questionnaires and airway responsiveness measurements in epidemiological studies. A sizeable number of subjects can be identified with intermediate levels of airway responsiveness, who are able to perceive bronchoconstriction and are familiar with the sensations associated with it, yet who are not recognized to suffer from asthma.
Cable parameters, sodium, potassium, chloride, and water content, and potassium efflux in isolated external intercostal muscle of normal volunteers and patients with myotonia congenita
Authors: R. J. Lipicky, S. H. Bryant, J. H. Salmon
Journal: Journal of Clinical Investigation (1971)

In isolated fiber bundles of external intercostal muscle from each of 13 normal volunteers and each of 6 patients with myotonia congenita, some or all of the following were measured: concentrations of Na(+), K(+), and Cl(-), extracellular volume, water content, K(+) efflux, fiber size, fiber cable parameters, and fiber resting potentials. Muscle from patients with myotonia congenita differed significantly (0.001 <P< 0.025) with respect to the following mean values (myotonia congenita vs. normal): the membrane resistance was greater (5729 vs. 2619 omega.cm(2)), the internal resistivity was less (75.0 vs. 123.2 omega.cm), the water content was less (788.2 vs. 808.2 ml/kg wet weight), and the mean resting potential was greater (68 vs. 61 mv).NO SIGNIFICANT DIFFERENCES WERE FOUND WITH RESPECT TO THE FOLLOWING VARIABLES: K(+) content (73.5 vs. 66.7 mEq/kg wet weight) and the calculated intracellular K(+) concentration (215 vs. 191 mEq/liter fiber water), fiber capacitance (5.90 vs. 5.15 muf/cm(2)), Na(+) content (97.7 vs. 94.1 mEq/kg wet weight), Cl(-) content (79.0 vs. 74.7 mEq/kg wet weight), mannitol extracellular volume (45.1 vs. 46.6 cc/100 g wet weight), and K(+) efflux (23.2 vs. 21.5 moles x 10(-12) cm(-2).sec(-1)). These abnormalities of skeletal muscle in human myotonia congenita are like those of skeletal muscle in goats with hereditary myotonia. We tentatively conclude that a decreased Cl(-) permeability accounts for some of the abnormal electrical properties of skeletal muscle in myotonia congenita.
CLINICAL AND EPIDEMIOLOGICAL ASPECTS OF THE DERMAL TUMBU-FLY-MYIASIS IN EQUATORIAL-AFRICA*
Authors: S. GUNTHER
Journal: British Journal of Dermatology (1971)

SUMMARY.— The term myiasis covers a group of diseases which are caused in man and other vertebrates by the larvae of dipterous insects. According to the localization of the larvae in the organism 2 main forms may be distinguished, internal and external myiasis. The dermal Tumbu- fly-myiasis occurs normally only in Equatorial Africa; but, with the increasing use of air travel, cases have been seen in Europe. The epidemiology, clinical features and treatment of this disease are discussed.
Glycosylation and Size of IgA1 Are Essential for Interaction with Mesangial Transferrin Receptor in IgA Nephropathy
Authors: Ivan C. Moura, Michelle Arcos-Fajardo, Charlotte Sadaka, Valérie Leroy, Marc Benhamou, Jan Novak, Franc[COMBINING CEDILLA]ois Vrtovsnik, Elie Haddad, Koteswara R. Chintalacharuvu, Renato C. Monteiro
Journal: Journal of the American Society of Nephrology (2004)

ABSTRACT. Transferrin receptor (TfR) has been identified as a candidate IgA1 receptor expressed on human mesangial cells (HMC). TfR binds IgA1 but not IgA2, co-localizes with mesangial IgA1 deposits, and is overexpressed in patients with IgA nephropathy (IgAN). Here, structural requirements of IgA1 for its interaction with mesangial TfR were analyzed. Polymeric but not monomeric IgA1 interacted with TfR on cultured HMC and mediates internalization. IgA1 binding was significantly inhibited (>50%) by soluble forms of both TfR1 and TfR2, confirming that TfR serves as mesangial IgA1 receptor. Hypogalactosylated serum IgA1 from patients with IgAN bound TfR more efficiently than IgA1 from healthy individuals. Serum IgA immune complexes from patients with IgAN containing aberrantly glycosylated IgA1 bound more avidly to TfR than those from normal individuals. This binding was significantly inhibited by soluble TfR, highlighting the role of TfR in mesangial IgA1 deposition. For addressing the potential role of glycosylation sites in IgA1-TfR interaction, a variety of recombinant dimeric IgA1 molecules were used in binding studies on TfR with Daudi cells that express only TfR as IgA receptor. Deletion of either N- or O-linked glycosylation sites abrogated IgA1 binding to TfR, suggesting that sugars are essential for IgA1 binding. However, sialidase and β-galactosidase treatment of IgA1 significantly enhanced IgA1/TfR interaction. These results indicate that aberrant glycosylation of IgA1 as well as immune complex formation constitute essential factors favoring mesangial TfR–IgA1 interaction as initial steps in IgAN pathogenesis.
Microscopic colitis syndrome.
Authors: B Veress, R Lofberg, L Bergman
Journal: Gut (1995)

The colorectal biopsy specimens from 30 patients with chronic watery diarrhoea but normal endoscopic and radiographic findings were studied by light microscopy, morphometry, immunohistochemistry, and two patients with electron microscopy. The histological changes in the colorectum were originally diagnosed in six patients as lymphocytic colitis and in 24 patients as collagenous colitis. The analysis of the specimens for this study could delineate three distinct groups of microscopic colitis: lymphocytic colitis (six patients), collagenous colitis without lymphocytic attack on the surface epithelium (seven patients), and a mixed form presenting with both thickening of the collagen plate and increased number of intraepithelial lymphocytes (17 patients). No transformation was seen from one type to another during follow up of six patients for four to seven years. Increased numbers of active pericryptal myofibroblasts were found with the electron microscope in one patient with mixed microscopic colitis showing also myofibroblasts entrapped within the collagen layer. Hitherto undescribed flat mucosa of the ileum was found in one patient with lymphocytic colitis and both flat mucosa and thickening of the collagen plate in the ileum were seen in one patient with the mixed form of the disease. In another patient with mixed microscopic colitis, normalisation of the colorectal morphology occurred after temporary loop ileostomy, followed by the reappearance of both diarrhoea, inflammation, and thickening of the collagen plate after the ileostomy was reversed. No association was found between non-steroid anti-inflammatory drug (NSAID) consumption and collagenous or mixed microscopic colitis. The primary cause of microscopic colitis is probably an immunological reaction to luminal antigen/s, perhaps of ileal origin. The engagement of the pericryptal myofibroblasts in the disease process might result in the development of the various forms of microscopic colitis. An inverse relation between intraepithelial lymphocyte count and collagen thickness may indicate that microscopic colitis is a spectral disease.
Renal L-Type Fatty Acid–Binding Protein in Acute Ischemic Injury
Authors: Tokunori Yamamoto, Eisei Noiri, Yoshinari Ono, Kent Doi, Kousuke Negishi, Atsuko Kamijo, Kenjiro Kimura, Toshiro Fujita, Tsuneo Kinukawa, Hideki Taniguchi, Kazuo Nakamura, Momokazu Goto, Naoshi Shinozaki, Shinichi Ohshima, Takeshi Sugaya
Journal: Journal of the American Society of Nephrology (2007)

Fatty acid-binding proteins (FABPs) bind unsaturated fatty acids and lipid peroxidation products during tissue injury from hypoxia. We evaluated the potential role of L-type FABP (L-FABP) as a biomarker of renal ischemia in both human kidney transplant patients and animal models. Urinary L-FABP levels were measured in the first urine produced from 12 living-related kidney transplant patients immediately after reperfusion of their transplanted organs, and intravital video analysis of peritubular capillary blood flow was performed simultaneously. A significant direct correlation was found between urinary L-FABP level and both peritubular capillary blood flow and the ischemic time of the transplanted kidney (both P < 0.0001), as well as hospital stay (P < 0.05). In human-L-FABP transgenic mice subjected to ischemia-reperfusion injury, immunohistological analyses demonstrated the transition of L-FABP from the cytoplasm of proximal tubular cells to the tubular lumen. In addition, after injury, these transgenic mice demonstrated lower blood urea nitrogen levels and less histological injury than injured wild-type mice, likely due to a reduction of tissue hypoxia. In vitro experiments using a stable cell line of mouse proximal tubule cells transfected with h-L-FABP cDNA showed reduction of oxidative stress during hypoxia compared to untransfected cells. Taken together, these data show that increased urinary L-FABP after ischemic-reperfusion injury may find future use as a biomarker of acute ischemic injury.
Response to Letter Regarding Article, “Mortality Associated With Atrial Fibrillation in Patients With Myocardial Infarction: A Systematic Review and Meta-Analysis”
Authors: Patricia Jabre, Véronique L. Roger, Mohammad H. Murad, Alanna M. Chamberlain, Larry Prokop, Frédéric Adnet, Xavier Jouven
Journal: Circulation (2011)