tbuckley/cabot-search huggingface dataset:
Doing the Right Things and Doing Them the Right Way
Authors: Rajendra H. Mehta, Anita Y. Chen, Karen P. Alexander, E. Magnus Ohman, Matthew T. Roe, Eric D. Peterson
Journal: Circulation (2015)

Background— Performance metrics currently focus on the measurement of the application of guideline-indicated medications without considering the appropriate dosing of these drugs. Methods and Results— We studied 39 291 patients from the Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes with Early Implementation of the ACC/AHA Guidelines (CRUSADE) registry with non–ST-segment elevation acute coronary syndromes. We evaluated hospital variability in the composite use of American College of Cardiology/American Heart Association guideline–recommended therapies (adherence) and the proportion of treated patients with the recommended dose of heparins or a glycoprotein IIb/IIIa antagonist (safety), and its association with risk-adjusted in-hospital mortality and bleeding. The rates of composite guideline adherence (median, 85%; 25th, 75th percentile, 82, 88) and antithrombotic dosing safety (median, 53%; 25th, 75th percentile, 45%, 60%) varied among hospitals. Correlation between hospital composite adherence and safety metrics was significant but low ( r =0.16, P =0.008). Risk-adjusted in-hospital mortality was inversely related to both guideline adherence (odds ratio-10% increment, 0.80; 95% confidence interval, 0.67–0.94) and safety metrics (odds ratio-10% increment, 0.90; 95% confidence interval, 0.83–0.98). Safety was inversely related to major bleeding (adjusted odds ratio-10% increment, 0.93; 95% confidence interval, 0.87–0.98). In comparison with hospitals with low adherence and safety (≤median performance) metrics, those with mixed performance metrics (high adherence and low safety, low adherence and high safety) had intermediate risk-adjusted mortality rates, whereas hospitals with above-average performance on both metrics (&gt;median performance) had a trend for lowest risk adjusted mortality rates (odds ratio 0.83; 95% confidence interval, 0.68–1.01). Hospitals with high safety had lower bleeding rates in comparison to those with low safety. Conclusions— Guideline adherence and dosing safety appeared to provide independent and complementary information on hospital bleeding and mortality, supporting the need for broader metrics of quality that should include measures of both guideline-based care and safety.
Current Status of the Epidemiologic Evidence Linking Polychlorinated Biphenyls and Non-Hodgkin Lymphoma, and the Role of Immune Dysregulation
Authors: Shira Kramer, Stephanie Moller Hikel, Kristen Adams, David Hinds, Katherine Moon
Journal: Environmental Health Perspectives (2012)

Although case-control studies conducted to date have largely affirmed the relationship between polychlorinated biphenyls (PCBs) and non-Hodgkin lymphoma (NHL), occupational cohort studies of PCB-exposed workers have been generally interpreted as negative, thereby raising doubts about a potential causal association. A common theme of immune dysregulation unifies many of NHL's strongest risk factors, and several authors have posited that subclinical immune dysregulation may increase NHL risk by decreasing host resistance, reducing control of cellular proliferation and differentiation, and diminishing tumor surveillance mechanisms.The goals of this review were a) to evaluate the epidemiological research examining the association between PCB exposure and NHL and discuss the contribution to the weight of evidence of case-control studies and occupational cohort studies; and b) to summarize the evidence for immune dysregulation as a means by which PCBs may cause NHL.We performed a literature search using PubMed and seven additional online biomedical and toxicological referencing libraries to identify literature published through August 2011.Overall, we conclude that the weight of evidence supports a causal role of PCBs in lymphomagenesis. The strongest epidemiological evidence for the relationship between PCBs and NHL comes from case-control studies conducted among the general population. Epidemiological and toxicological data demonstrating immunosuppressive and inflammatory effects of PCBs further contribute to the weight of evidence by providing a plausible explanation for how PCBs can cause NHL through immune dysregulation.
Reply to ‘ATM variants and predisposition to childhood T-lineage acute lymphoblastic leukaemia’ by Gumy-Pause et al.
Authors: M Meier, M L den Boer, A G Hall, J A E Irving, M Passier, L Minto, E R van Wering, G E Janka-Schaub, R Pieters
Journal: Leukemia (2006)
2,665 Cases of Abortion
Authors: A. Davis
Journal: BMJ (1950)

This review is based on a series of consecutive cases of abortion under my care at St. Giles' and Dulwich Hospitals, London.The two hospitals are relatively closely situated in a working-class suburb, with approximately the same number of gynaecological beds, under the same consultative direction.They therefore offer excellent opportunity for comparison of different methods of treatment, for these can be carried out under fairly comparable conditions.During the past 15 years (with the exception of a wartime interval) advantage has been taken of this opportunity to assess the value of varying treatments, and it was the primary object of the present investigation to determine the relative merits of active and passive treatment in cases of incomplete abortion, and to settle, if possible, some of the issues of this perennial source of argument.A second object was to compare the potency (if any) of different chemotherapeutic agents in infected cases.For these purposes a detailed analysis was made of enough cases to reduce percentage error to a reasonable minimum-the actual number recommended by our statistical adviser was 2,500, and this has been only slightly exceeded, the cases being almost evenly divided between the two hospitals con- cerned.The results of this analysis are given below, and it is suggested that they are definite enough to be of thera- peutic significance.During the course of this investigation various secondary factors-age, parity, morbidity, etc.-had necessarily to be considered.These proved of sufficient interest to merit analysis, and they are classified below under the appropriate headings. AgeThe average age of the patients was 29 years, the youngest being 17 and the oldest 49.This corresponds with the figures given by Gellert (1926), who found the average age between 20 and 30 years; only 3 % of his cases were younger than 20 years.Similarly, the report of the Children's Bureau of New York (1934) gives an average of 25 to 29 years.
Development, pharmacology and clinical experience with clomiphene citrate
Authors: R. Dickey
Journal: Human Reproduction Update (1996)

This review describes the development and pharmacology of clomiphene and those specific characteristics of both drug and patients which determine its clinical efficacy. The studies reviewed describe clinical observation of patient characteristics (age, additional infertility diagnosis, semen quality), vaginal ultrasound observations of ovaries (number and size of pre-ovulatory follicles) and endometrial lining (thickness, pattern) in 2841 clomiphene cycles in patients who required intrauterine insemination (IUI) because of poor sperm quality or an unsatisfactory postcoital test. They show that (I) conception in clomiphene cycles is related to the number and size of pre-ovulatory follicles, endometrial thickness, patient age, pelvic adhesions, type of anovulatory disorder and semen quality; (ii) pregnancy rates per clomiphene-IUI cycle are constant through at least six cycles; (iii) multiple births cannot be prevented by withholding human chorionic gonadotrophin or advising against coitus when multiple pre-ovulation follicles are present unless all follicles down to 10-12 mm diameter are counted. We also reviewed pregnancy outcome (number of gestational sacs, babies, preclinical and clinical abortion, ectopic pregnancy and birth sex) in 1744 clomiphene pregnancies from our clinic. We found that (I) preclinical and clinical abortions are increased only slightly by clomiphene use, compared to spontaneous pregnancy; (ii) clinical abortions are decreased in patients with polycystic ovaries and luteal insufficiency who use clomiphene; (iii) conception and preclinical abortions are related to endometrial thickness prior to ovulation; (iv) ectopic pregnancies are not increased by clomiphene and (v) the ratio of male births is not altered by clomiphene, except possibly in timed insemination cycles. These studies repudiate many misconceptions regarding clomiphene. They also show that clinical outcome may be improved by pre-ovulation ultrasound monitoring of ovarian and endometrial response.
Smad-Dependent and Smad-Independent Induction of Id1 by Prostacyclin Analogues Inhibits Proliferation of Pulmonary Artery Smooth Muscle Cells In Vitro and In Vivo
Authors: Jun Yang, Xiaohui Li, Rafia S. Al-Lamki, Mark Southwood, Jing Zhao, Andrew M. Lever, Friedrich Grimminger, Ralph T. Schermuly, Nicholas W. Morrell
Journal: Circulation Research (2010)

Rationale : Mutations in the bone morphogenetic protein type II receptor (BMPR-II) are responsible for the majority of cases of heritable pulmonary arterial hypertension (PAH). Mutations lead to reduced Smad1/5-driven expression of inhibitor of DNA binding protein 1 (Id1) and loss of the growth suppressive effects of BMPs. The impact of existing PAH therapies on BMP signaling is lacking. Objective : Because prostacyclin analogues are effective treatments for clinical PAH, we hypothesized that these agents enhance Smad1/Id1 signaling. Methods and Results : Iloprost alone induced Id1 expression in human pulmonary artery smooth muscle cells (PASMCs), an effect that was independent of Smad1/5 activation but dependent on a cAMP-responsive element in the Id1 promoter. In addition, iloprost and treprostinil enhanced BMP-induced phosphorylation of Smad1/5 and Id1 expression in a cAMP-dependent manner. The mechanism involved suppression of inhibitory Smad, Smad6. Furthermore, iloprost rescued the deficit in Smad1/5 phosphorylation and Id gene expression in PASMCs harboring mutations in BMPR-II and restored growth suppression to BMP4 in mutant PASMCs. We confirmed a critical role for Id1 in PASMC proliferation. Reduced expression of Id1 was observed in concentric intimal lesions of heritable PAH cases. In the monocrotaline rat model of PAH, associated with reduced BMPR-II expression, we confirmed that treprostinil inhibited smooth muscle cell proliferation and prevented progression of PAH while enhancing Smad1/5 phosphorylation and Id1 gene expression. Conclusions : Prostacyclin analogues enhance Id1 expression in vitro and in vivo and restore deficient BMP signaling in BMPR-II mutant PASMCs.
Quinidine-lnduced Liver Disease?
Authors: PATRICK J. MURPHY
Journal: Annals of Internal Medicine (1973)

Comments and Corrections1 May 1973Quinidine-lnduced Liver Disease?PATRICK J. MURPHY, M.D., WILLIAM RYMER, M.D.PATRICK J. MURPHY, M.D.Search for more papers by this author, WILLIAM RYMER, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-78-5-785 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: Deisseroth, Morganroth, and Winokur reported an interesting case of quinidine-induced liver disease in the October issue (Ann Intern Med 77:595-597, 1972). This prompted us to reexamine a similar case.A 62-year-old man was admitted on 27 September 1972 to the Veterans' Administration Hospital in Madison, Wisconsin, with shortness of breath. His medical history included hypertension for approximately 10 years, treated with hydrochlorothiazide, and congestive heart failure for 2 years. Mild renal insufficiency had been noted for 6 years and was thought to be secondary to his hypertension.He had previously been admitted in December 1971 for fever... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: University of Wisconsin Hospitals Madison, Wisconsin PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByHepatotoxicity of Cardiovascular DrugsMore on Drug FeverJOSEPH HERMAN, M.D.Clinical Utilization of Alkaline Phosphatase MeasurementsDrug Information Analysis ServiceQuinidine, HepatotoxicityQuinidine Hypersensitivity and Liver InvolvementDrug Action, Reaction, and Interaction. I. Quinidine for Cardiac ArrhythmiasQuinidine-lnduced Granulomatous HepatitisT. CHAJEK, M.D., B. LEHRER, M.B., Ch.B., D. GELTNER, M.D., I. S. LEVIJ, M.D. 1 May 1973Volume 78, Issue 5Page: 785-786KeywordsDyspneaFeversHeart failureHypertensionLiver diseasesSecondary hypertension Issue Published: 1 May 1973 PDF DownloadLoading ...
Case 4-1983
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, Betty U. McNeely, Thomas J. Ryan, Thomas H. Aretz
Journal: New England Journal of Medicine (1983)

Presentation of CaseA 15-year-old girl was admitted to the hospital because of a murmur and a right ventricular mass.The patient was the third child of a mother 44 years of age; she was born of a normal pregnancy, labor, and delivery. Her growth, development, feeding, and activity were uneventful. At the age of four years a venous hum was heard but disappeared when she turned her head. Her later growth, activity, and health were normal. Annual examinations by her pediatrician showed no abnormality.Three weeks before admission a pediatrician heard a murmur and referred her to this hospital, . . .
Emerging β-Amyloid Pathology and Accelerated Cortical Atrophy
Authors: Niklas Mattsson, Philip S. Insel, Rachel Nosheny, Duygu Tosun, John Q. Trojanowski, Leslie M. Shaw, Clifford R. Jack, Michael C. Donohue, Michael W. Weiner
Journal: JAMA Neurology (2014)

The effect of β-amyloid (Aβ) accumulation on regional structural brain changes in early stages of Alzheimer disease (AD) is not well understood.To test the hypothesis that the development of Aβ pathology is related to increased regional atrophy in the brains of cognitively normal (CN) persons.Longitudinal clinicobiomarker cohort study involving 47 CN control subjects and 15 patients with AD dementia. All participants underwent repeated cerebrospinal fluid Aβ42 and structural magnetic resonance imaging measurements for up to 4 years. Cognitively normal controls were classified using the longitudinal cerebrospinal fluid Aβ42 data and included 13 stable Aβ negative (normal baseline Aβ42 levels, with less than the median reduction over time), 13 declining Aβ negative (normal baseline Aβ42 levels, with greater than the median reduction over time), and 21 Aβ positive (pathologic baseline Aβ42 levels). All 15 patients with AD dementia were Aβ positive.Group effects on regional gray matter volumes at baseline and over time, tested by linear mixed-effects models.Baseline gray matter volumes were similar among the CN Aβ groups, but atrophy rates were increased in frontoparietal regions in the declining Aβ-negative and Aβ-positive groups and in amygdala and temporal regions in the Aβ-positive group. Aβ-positive patients with AD dementia had further increased atrophy rates in hippocampus and temporal and cingulate regions.Emerging Aβ pathology is coupled to increased frontoparietal (but not temporal) atrophy rates. Atrophy rates peak early in frontoparietal regions but accelerate in hippocampus, temporal, and cingulate regions as the disease progresses to dementia. Early-stage Aβ pathology may have mild effects on local frontoparietal cortical integrity while effects in temporal regions appear later and accelerate, leading to the atrophy pattern typically seen in AD.
Metabolic and haemodynamic changes in the heart during the early phase of cardiopulmonary bypass: II. Animal experiments
Authors: F. H VAN DER VEEN, G. J VAN DER VUSSE, R. T I KRUGER, T. VAN DER NAGEL, P. WILLEMSEN, R. S RENEMAN
Journal: Cardiovascular Research (1989)

A significant release of lactate instead of uptake was observed during the first 10 min of cardiopulmonary bypass preceding aorto-coronary bypass surgery in human patients. To clarify these findings in more detail, myocardial lactate and oxygen metabolism was studied in healthy dog hearts subjected to a protocol similar to the clinical situation. In one group (n = 11) normothermia at 34 degrees C was used with an empty beating heart, and in the other group (n = 11) hypothermia with ventricular fibrillation was applied. Within the first 10 min of bypass no significant changes in high energy phosphates were observed in myocardial biopsies. However, a marked decrease in mean aortic blood pressure and a simultaneous lowering in oxygen consumption was observed in both groups after instalment of bypass. An initial shift from lactate uptake to lactate release occurred while on bypass in the normothermia group. After 10 min of bypass, lactate uptake was restored in hearts of both groups. Therefore, the lactate release during the initial phase of bypass in patients originates both from the instalment of the bypass and from (local) inadequate perfusion, which is most likely to be due to stenosed coronary arteries.
Autosomal dominant hypophosphatemic rickets is linked to chromosome 12p13.
Authors: M J Econs, P T McEnery, F Lennon, M C Speer
Journal: Journal of Clinical Investigation (1997)

Autosomal dominant hypophosphatemic rickets (ADHR) is an inherited disorder of isolated renal phosphate wasting, the pathogenesis of which is unknown. We performed a genome-wide linkage study in a large kindred to determine the chromosome location of the ADHR gene. Two-point LOD scores indicate that the gene is linked to the markers D12S314 [Z(theta) = 3.15 at theta = 0.0], vWf [Z(theta) = 5.32 at theta = 0.0], and CD4 [Z(theta) = 3.53 at theta = 0.0]. Moreover, multilocus analysis indicates that the ADHR gene locus is located on chromosome 12p13 in the 18-cM interval between the flanking markers D12S100 and D12S397. These data are the first to establish a chromosomal location for the ADHR locus and to provide a framework map to further localize the gene. Such studies will permit ultimate identification of the ADHR gene and provide further insight into phosphate homeostasis.
Increased expression of lipoxygenase enzymes during pollen season in nasal biopsies of pollen‐allergic patients
Authors: H. Plewako, K. Holmberg, I. Oancea, S. Rak
Journal: Allergy (2006)

Background: Exposure of patients sensitized to pollen triggers development of seasonal allergic rhinitis symptoms (SAR). Eicosanoids are a group of arachidonic acid metabolites contributing to the symptoms of SAR. The aim of this study was to investigate seasonal changes in the expression of enzymes of the eicosanoid pathway in the nasal mucosa of patients with SAR. Methods: Twenty SAR patients allergic to birch or grass and eight healthy subjects were included in the study. Patients registered rhinoconjunctivitis symptoms and use of rescue medication before and during the pollen season. Nasal biopsies were obtained before and around the peak of the season, sectioned and stained using markers for eosinophils, mast cells, T cells and neutrophils. Antibodies against the following enzymes were also used: cyclo‐oxygenase (COX‐1, COX‐2), 5‐lipoxygenase (5‐LO), 5‐lipoxygenase‐activating factor (FLAP), LTA 4 hydrolase (LTA 4 h) and LTC 4 synthase (LTC 4 s). Results: During the pollen season symptoms of rhinoconjunctivitis and medication score increased significantly ( P = 0.001; P = 0.001 respectively). During the pollen season numbers of eosinophils ( P = 0.02) and cell positive 5‐LO ( P = 0.02), LTC 4 s ( P = 0.04) and LTA 4 h ( P = 0.02) increased significantly. During season number of mast cells and cells expressing 5‐LO and LTA 4 h were higher in SAR than in healthy controls group ( P = 0.02; P = 0.01; P = 0.03 respectively). Conclusion: In sensitized patients exposure to pollen allergen results in increased expression of enzymes of the eicosanoid pathway.
Fetal growth and maternal exposure to particulate matter during pregnancy.
Authors: J Dejmek, S G Selevan, I Benes, I Solanský, R J Srám
Journal: Environmental Health Perspectives (1999)

Prior studies reported an association between ambient air concentrations of total suspended particles and SO2 during pregnancy and adverse pregnancy outcomes. We examined the possible impact of particulate matter up to 10 microm (PM10) and up to 2.5 microm (PM2. 5) in size on intrauterine growth retardation (IUGR) risk in a highly polluted area of Northern Bohemia (Teplice District). The study group includes all singleton full-term births of European origin over a 2-year period in the Teplice District. Information on reproductive history, health, and lifestyle was obtained from maternal questionnaires. The mean concentrations of pollutants for each month of gestation were calculated using continuous monitoring data. Three intervals (low, medium, and high) were constructed for each pollutant (tertiles). Odds ratios (ORs) for IUGR for PM10 and PM2.5 levels were generated using logistic regression for each month of gestation after adjustment for potential confounding factors. Adjusted ORs for IUGR related to ambient PM10 levels in the first gestational month increased along the concentration intervals: medium 1.62 [95% confidence interval (CI), 1.07-2.46], high 2.64 (CI, 1.48-4.71). ORs for PM2.5 were 1.26 (CI, 0.81-1.95) and 2.11 (CI, 1. 20-3.70), respectively. No other associations of IUGR risk with particulate matter were found. Influence of particles or other associated air pollutants on fetal growth in early gestation is one of several possible explanations of these results. Timing of this effect is compatible with a current hypothesis of IUGR pathogenesis. Seasonal factors, one of the other possible explanations, is less probable. More investigation is required to examine these findings and alternative explanations.
Asthma in Respiratory Therapists
Authors: David G. Kern
Journal: Annals of Internal Medicine (1989)

Study Objective: To test the hypothesis that work as a respiratory therapist is associated with an increased risk of developing asthma. Design: Cross-sectional questionnaire study comparing respiratory therapists with controls (physical therapists and radiologic technologists). Subsequent validation of reported asthma with methacholine challenge studies. Subjects: All respiratory therapists and physical therapists and a random 50% sample of radiologic technologists working in the state of Rhode Island as of June 1986. Methods: All subjects received a mail questionnaire with questions about the presence or absence of asthma, time of onset, and important covariates. Responses were analyzed for all subjects, and again after excluding those subjects with pre-existing asthma. Subjects who reported physician-diagnosed asthma were asked to have methacholine challenge testing. Results: Respondents included 194 respiratory therapists (response rate, 69.5%) and 517 controls (response rate, 75.3%). After excluding respiratory therapists from the hospital at which the hypothesis was generated, there were 34 respiratory therapists (18.7%) and 30 controls (5.8%) reporting physician-diagnosed asthma. After controlling for age, smoking status, family history, atopic history, and other covariates using logistic regression, respiratory therapy carried an odds ratio of 3.2 (95% CI, 1.9 to 5.5). With analysis restricted to those who developed asthma after entering their profession, the odds ratio for respiratory therapy was 4.6 (95% CI, 2.0 to 10.4). In the validation study, 10 of 14 respiratory therapists (71%) and 6 of 10 controls (60%) had evidence of bronchial hyperreactivity. Conclusions: These results suggest a previously unrecognized excess of asthma in respiratory therapists. The excess develops after entry into the profession, and does not appear to be explained by confounding, information bias, or selection bias.