tbuckley/cabot-search huggingface dataset:
Risk Factors and Secondary Prevention in Women with Heart Disease: The Heart and Estrogen/progestin Replacement Study
Authors: Eric Vittinghoff, Michael G. Shlipak, Paul D. Varosy, Curt D. Furberg, Christine C. Ireland, Steven S. Khan, Roger Blumenthal, Elizabeth Barrett-Connor, Stephen Hulley
Journal: Annals of Internal Medicine (2003)

Background: Risk factors for coronary heart disease events have most commonly been evaluated in healthy men. Objective: To assess risk factors, event rates, and use of secondary prevention treatments in women with preexisting coronary disease. Design: A prospective cohort of clinical trial participants. Setting: 20 U.S. clinical centers. Participants: 2763 postmenopausal women with known coronary disease in the Heart and Estrogen/progestin Replacement Study (HERS). Measurements: Myocardial infarction or death from coronary heart disease. Results: On multivariable analysis, the researchers found 11 risk factors: 6 noted by history (nonwhite ethnicity, lack of exercise, treated diabetes, angina, congestive heart failure, and more than one previous myocardial infarction) and 5 that were measured (blood pressure, low-density lipoprotein cholesterol level, high-density lipoprotein cholesterol level, lipoprotein[a] level, and creatinine clearance). The annual rate of coronary events was 1.3% (95% CI, 0.7% to 2.5%) in women with no risk factors and 8.7% (CI, 7.1% to 10.8%) in women with five or more risk factors (a sixfold increase). At entry into HERS, 83% of participants were receiving aspirin or other antiplatelet agents, 33% were receiving -blockers, 18% were receiving angiotensin-converting enzyme inhibitors, and 53% were receiving lipid-lowering drugs. Women with more risk factors were less likely to be taking aspirin (P < 0.001) and lipid-lowering drugs (P = 0.006). Conclusions: Women with coronary disease are at high risk for myocardial infarction or death from coronary heart disease even in the absence of other risk factors, and their risk increases up to sixfold when many risk factors are present. Established drugs for secondary prevention, including aspirin, -blockers, and lipid-lowering agents, are underused in these women, especially those at highest risk.
Mutations in SLC34A3/NPT2c Are Associated with Kidney Stones and Nephrocalcinosis
Authors: Debayan Dasgupta, Mark J. Wee, Monica Reyes, Yuwen Li, Peter J. Simm, Amita Sharma, Karl-Peter Schlingmann, Marco Janner, Andrew Biggin, Joanna Lazier, Michaela Gessner, Dionisios Chrysis, Shamir Tuchman, H. Jorge Baluarte, Michael A. Levine, Dov Tiosano, Karl Insogna, David A. Hanley, Thomas O. Carpenter, Shoji Ichikawa, Bernd Hoppe, Martin Konrad, Lars Sävendahl, Craig F. Munns, Hang Lee, Harald Jüppner, Clemens Bergwitz
Journal: Journal of the American Society of Nephrology (2014)

Compound heterozygous and homozygous (comp/hom) mutations in solute carrier family 34, member 3 (SLC34A3), the gene encoding the sodium (Na+)-dependent phosphate cotransporter 2c (NPT2c), cause hereditary hypophosphatemic rickets with hypercalciuria (HHRH), a disorder characterized by renal phosphate wasting resulting in hypophosphatemia, correspondingly elevated 1,25(OH)2 vitamin D levels, hypercalciuria, and rickets/osteomalacia. Similar, albeit less severe, biochemical changes are observed in heterozygous (het) carriers and indistinguishable from those changes encountered in idiopathic hypercalciuria (IH). Here, we report a review of clinical and laboratory records of 133 individuals from 27 kindreds, including 5 previously unreported HHRH kindreds and two cases with IH, in which known and novel SLC34A3 mutations (c.1357delTTC [p.F453del]; c.G1369A [p.G457S]; c.367delC) were identified. Individuals with mutations affecting both SLC34A3 alleles had a significantly increased risk of kidney stone formation or medullary nephrocalcinosis, namely 46% compared with 6% observed in healthy family members carrying only the wild-type SLC34A3 allele (P=0.005) or 5.64% in the general population (P<0.001). Renal calcifications were also more frequent in het carriers (16%; P=0.003 compared with the general population) and were more likely to occur in comp/hom and het individuals with decreased serum phosphate (odds ratio [OR], 0.75, 95% confidence interval [95% CI], 0.59 to 0.96; P=0.02), decreased tubular reabsorption of phosphate (OR, 0.41; 95% CI, 0.23 to 0.72; P=0.002), and increased serum 1,25(OH)2 vitamin D (OR, 1.22; 95% CI, 1.05 to 1.41; P=0.008). Additional studies are needed to determine whether these biochemical parameters are independent of genotype and can guide therapy to prevent nephrocalcinosis, nephrolithiasis, and potentially, CKD.
Biallelic and Heterozygous Point Mutations in the Runt Domain of theAML1/PEBP2B Gene Associated With Myeloblastic Leukemias
Authors: Motomi Osato, Norio Asou, Essam Abdalla, Koyu Hoshino, Hiroshi Yamasaki, Toshiya Okubo, Hitoshi Suzushima, Kiyoshi Takatsuki, Tomohiko Kanno, Katsuya Shigesada, Yoshiaki Ito
Journal: Blood (1999)
Lithium Placental Passage and Obstetrical Outcome: Implications for Clinical Management During Late Pregnancy
Authors: D. Jeffrey Newport, Adele C. Viguera, Aquila J. Beach, James C. Ritchie, Lee S. Cohen, Zachary N. Stowe
Journal: American Journal of Psychiatry (2005)

OBJECTIVE: Lithium has been used during pregnancy for more than four decades, but quantification of fetal lithium exposure and clinical correlations of such exposure are limited. The study objectives were to 1) quantify the rate of lithium placental passage, 2) assess any association between plasma concentration of lithium at delivery and adverse perinatal events, and 3) determine whether lithium concentrations can be reduced by briefly suspending therapy proximate to delivery. METHOD: Maternal blood and umbilical cord blood were obtained at delivery for assay of lithium concentrations, and obstetrical outcome data were collected prospectively for 10 participants. These data were combined with results from MEDLINE and PsycINFO searches that identified 32 cases in which maternal lithium was administered throughout delivery. Statistical analysis of the pooled data was conducted. RESULTS: The ratio of lithium concentrations in umbilical cord blood to maternal blood (mean=1.05, SD=0.13) was uniform across a wide range of maternal concentrations (0.2–2.6 meq/liter). Significantly lower Apgar scores, longer hospital stays, and higher rates of CNS and neuromuscular complications were observed in infants with higher lithium concentrations (>0.64 meq/liter) at delivery. Withholding lithium therapy for 24–48 hours before delivery resulted in a 0.28 meq/liter reduction in maternal lithium concentration. CONCLUSIONS: Lithium completely equilibrates across the placenta. Higher lithium concentrations at delivery are associated with more perinatal complications, and lithium concentrations can be reduced by brief suspension of therapy proximate to delivery. Treatment guidelines are proposed to improve neonatal well-being when lithium use is indicated in late pregnancy.
Arm Edema in Breast Cancer Patients
Authors: V. S. Erickson, M. L. Pearson, P. A. Ganz, J. Adams, K. L. Kahn
Journal: JNCI Journal of the National Cancer Institute (2001)

The improvement in the life expectancy of women with breast cancer raises important questions about how to improve the quality of life for women sustaining complications of breast cancer treatment. In particular, attention to common problems, such as arm edema, is of critical importance. We reviewed published breast cancer guidelines and literature identified via MEDLINE® searches in an effort to summarize the research literature pertinent to management of breast cancer-related arm edema, including incidence, prevalence, and timing; risk factors; morbidity; prevention; diagnosis; and efficacy of nonpharmacologic and pharmacologic interventions. We found that arm edema is a common complication of breast cancer therapy that can result in substantial functional impairment and psychological morbidity. The risk of arm edema increases when axillary dissection and axillary radiation therapy are used. Recommendations for preventive measures, such as avoidance of trauma, are available, but these measures have not been well studied. Nonpharmacologic treatments, such as massage and exercise, have been shown to be effective therapies for lymphedema, but the effect of pharmacologic interventions remains uncertain. Comparing results across studies is complicated by the fact that the definitions of interventions and measures of outcomes and risk stratification vary substantially among studies. As arm edema becomes more prevalent with the increasing survival of breast cancer patients, further research is needed to evaluate the efficacy of preventive strategies and therapeutic interventions.
Challenges in Projecting Clustering Results Across Gene Expression–Profiling Datasets
Authors: Lara Lusa, Lisa M. McShane, James F. Reid, Loris De Cecco, Federico Ambrogi, Elia Biganzoli, Manuela Gariboldi, Marco A. Pierotti
Journal: JNCI Journal of the National Cancer Institute (2007)

BackgroundGene expression microarray studies for several types of cancer have been reported to identify previously unknown subtypes of tumors. For breast cancer, a molecular classification consisting of five subtypes based on gene expression microarray data has been proposed. These subtypes have been reported to exist across several breast cancer microarray studies, and they have demonstrated some association with clinical outcome. A classification rule based on the method of centroids has been proposed for identifying the subtypes in new collections of breast cancer samples; the method is based on the similarity of the new profiles to the mean expression profile of the previously identified subtypes.
Improved survival outcomes with the incidental use of beta-blockers among patients with non-small-cell lung cancer treated with definitive radiation therapy
Authors: H.M. Wang, Z.X. Liao, R. Komaki, J.W. Welsh, M.S. O'Reilly, J.Y. Chang, Y. Zhuang, L.B. Levy, C. Lu, D.R. Gomez
Journal: Annals of Oncology (2013)
Benefits of Early Versus Delayed Palliative Care to Informal Family Caregivers of Patients With Advanced Cancer: Outcomes From the ENABLE III Randomized Controlled Trial
Authors: J. Nicholas Dionne-Odom, Andres Azuero, Kathleen D. Lyons, Jay G. Hull, Tor Tosteson, Zhigang Li, Zhongze Li, Jennifer Frost, Konstantin H. Dragnev, Imatullah Akyar, Mark T. Hegel, Marie A. Bakitas
Journal: Journal of Clinical Oncology (2015)

To determine the effect of early versus delayed initiation of a palliative care intervention for family caregivers (CGs) of patients with advanced cancer.
ELECTRON MICROSCOPIC LOCALIZATION OF IMMUNOGLOBULIN E ON THE SURFACE MEMBRANE OF HUMAN BASOPHILS
Authors: Albert L. Sullivan, Philip M. Grimley, Henry Metzger
Journal: The Journal of Experimental Medicine (1971)

We have examined human leukocyte preparations for the presence of surface-bound IgE by electron microscopy. Basophil-enriched leukocytes were reacted with burro anti-IgE, a hybrid antibody to burro IgG and ferritin, and ferritin, with or without prior incubation of the cells with an IgE myeloma protein. In the absence of preincubation with IgE small amounts of ferritin were fixed to the surface of basophils but on no other cells. When cells were preincubated with IgE the amount of ferritin fixation on the basophils was markedly increased and a small amount of ferritin was also bound to platelets but again to no other leukocytes. The distribution of ferritin on the basophil surface appeared dependent upon the temperature at which the cells were kept during and after reaction with the various reagents. Basophil sections from cells kept at 0 degrees C had ferritin bound to the surface membrane in patches distributed around the entire circumference. Basophil sections from cells prepared at room temperature had ferritin distributed assymetrically covering a surface membrane segment one-fifth to one-half of the circumference. In control studies in which monomeric IgG was substituted for the IgE and burro anti-IgG was used instead of burro anti-IgE, no cellular fixation of ferritin was observed.
Association Between Prediagnostic IgE Levels and Risk of Glioma
Authors: J. Schwartzbaum, B. Ding, T. B. Johannesen, L. T. N. Osnes, L. Karavodin, A. Ahlbom, M. Feychting, T. K. Grimsrud
Journal: JNCI Journal of the National Cancer Institute (2012)

Previous nested case–control studies suggest that a prediagnostic biomarker of allergy, IgE, is inversely associated with the risk of glioma, but these findings are inconsistent. The purpose of our study was to assess this association and determine how long before glioma diagnosis it may be observed. We conducted a nested case–control study using serum specimens from the Janus Serum Bank cohort in Norway. Blood donors who were subsequently diagnosed with glioma (n = 594 case subjects), between January 1, 1974 to December 31, 2007, were matched with subjects without glioma (n = 1177 control subjects) for date of blood collection, 2-year age interval at blood collection, and sex. Respiratory allergen-specific and total IgE levels in the serum were measured using fluorescent assays. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression models stratified on sex and glioblastoma, the most common glioma subtype. Data were stratified on time from blood collection to tumor diagnosis to assess how long before glioma diagnosis the association could be observed. Among women, testing positive for allergen-specific IgE (>0.35 kU A /L) was associated with decreased risk of glioblastoma compared with testing negative (≤0.35 kU A /L; OR = 0.46, 95% CI = 0.23 to 0.93). Among both sexes combined, testing positive for total IgE (>100 kU/L) was associated with decreased risk of glioma compared with testing negative (≤100 kU/L; OR = 0.75, 95% CI = 0.56 to 0.99), and simultaneously testing positive for allergen-specific IgE and total IgE was associated with a borderline statistically significantly decreased risk of glioblastoma and glioma compared with simultaneously testing negative for these types of IgE. Testing positive for total IgE at least 20 years before diagnosis was associated with decreased risk of glioma compared with testing negative (OR = 0.54, 95% CI = 0.30 to 0.99). An inverse association between IgE levels and risk of glioma was detected; the association was present at least 20 years before tumor diagnosis.
Glycemic Variability: Assessing Glycemia Differently and the Implications for Dietary Management of Diabetes
Authors: Jeannie Tay, Campbell H. Thompson, Grant D. Brinkworth
Journal: Annual Review of Nutrition (2015)

The primary therapeutic target for diabetes management is the achievement of good glycemic control, of which glycated hemoglobin (HbA1c) remains the standard clinical marker. However, glycemic variability (GV; the amplitude, frequency, and duration of glycemic fluctuations around mean blood glucose) is an emerging target for blood glucose control. A growing body of evidence supports GV as an independent risk factor for diabetes complications. Several techniques have been developed to assess and quantify intraday and interday GV. Additionally, GV can be influenced by several nutritional factors, including carbohydrate quality, quantity; and distribution; protein intake; and fiber intake. These factors have important implications for clinical nutrition practice and for optimizing blood glucose control for diabetes management. This review discusses the available evidence for GV as a marker of glycemic control and risk factor for diabetes complications. GV quantification techniques and the influence of nutritional considerations for diabetes management are also discussed.
Idiopathic impaired spermatogenesis: genetic epidemiology is unlikely to provide a short-cut to better understanding
Authors: Judith Gianotten, M.Paola Lombardi, A.H. Zwinderman, Richard J. Lilford, Fulco van der Veen
Journal: Human Reproduction Update (2004)

The aetiology of impaired spermatogenesis is unknown in the majority of subfertile men. From several studies of concordance for involuntary childlessness among men, we can conclude that there is a substantial familial component in male subfertility and that shared loci segregating through families can be assumed. We now know that deletions on the Y chromosome, which do not penetrate fully, account for some of these cases. There are good reasons to suspect that other cases result from mutations in genes located elsewhere in the genome. In this article, we discuss different approaches to unravelling the molecular basis of impaired spermatogenesis originating from genetic abnormalities in chromosomes other than the Y chromosome. Genetic mapping studies are in general a good approach to detect disease-causing genes that are segregating through a population; they can provide a shortcut to unravelling the biochemistry of a disease. In this paper, we explain our reasons for arguing that linkage and association studies are no promising means to identify the genes causing impaired spermatogenesis. We conclude that direct screening of candidate genes for mutations will be necessary to detect genes involved in impaired spermatogenesis. However, this approach requires studies of the biochemical pathways of normal and abnormal spermatogenesis. Since we have a poor understanding of these pathways, more research is needed into the biochemistry of spermatogenesis.
The respiratory response to CO2 and O2 in patients with coma due to voluntary intoxication with barbiturates and carbamates
Authors: S Launois, B Fleury, T Similowski, M Aubier, D Murciano, B Housset, R Pariente, JP Derenne
Journal: European Respiratory Journal (1990)

We have investigated the respiratory response to CO2 and to O2 in comatose subjects self intoxicated with barbiturates and carbamates. The chemical drive of 12 such patients with coma was compared with that of comparable normal subjects. The ventilatory response to CO2 was depressed but the P0.1 response was of the same order of magnitude as in normals. O2 had little effect on the ventilatory parameters and occlusion pressure. There was no difference between the two groups of patients, indicating that the respiratory changes observed were more dependent on the intensity of the intoxication than on the nature of the drugs. In addition, mechanical factors seem mainly responsible for the depressed ventilatory response to CO2.
Medicines and men: Burroughs, Wellcome &amp; Co, and the British drug industry before the Second World War
Authors: E M Tansey
Journal: Journal of the Royal Society of Medicine (2002)

Britain in the final decades of the nineteenth century was a vibrant market place for purveyors of medicines, including, inter alia, drug peddlars and travelling quacks, dispensing doctors and chemists, and established compounding companies such as Allen & Hanburys (est. 1715). Regulation and control of the manufacture, quality and efficacy of medicines were practically non-existent, and Weights and Measures and Poisons Acts were the principal relevant pieces of legislation.

During the same period, nationwide press and poster advertising, and the easier country-wide distribution of goods opened up by the railroads, contributed to the rise of the ‘branded’ commodity. Medicines, pills potions and nostrums were not exempt, and products such as Friar's Balsam, Wards Drop and Beechams Powders all achieved prominence and success in the second half of the nineteenth century. One such manufacturer, Thomas Holloway, was said to be spending £50 000 a year on advertising in 1883, the year of his death.

In Europe however, especially in Germany and Switzerland and to a lesser extent in France, several research-based scientific manufacturing companies were emerging. The rise of the dye industry in Germany, itself a byproduct of a coal-tar industry, provided a cadre of well qualified chemists whose scientific investigations of dye products led to the recognition of medicinal effects, and consequently to the creation of several pharmaceutical companies including Hoechst, Bayer, Sandoz and Ciba1. In Britain, the only company to engage seriously in such research activities was Burroughs, Wellcome & Co, founded in London in 1880 by two young American pharmacists.
Oral cysteamine bitartrate and N-acetylcysteine for patients with infantile neuronal ceroid lipofuscinosis: a pilot study
Authors: Sondra W Levin, Eva H Baker, Wadih M Zein, Zhongjian Zhang, Zenaide M N Quezado, Ning Miao, Andrea Gropman, Kurt J Griffin, Simona Bianconi, Goutam Chandra, Omar I Khan, Rafael C Caruso, Aiyi Liu, Anil B Mukherjee
Journal: The Lancet Neurology (2014)
Cardiac Dysfunction Caused by Myocardium-Specific Expression of a Mutant Thyroid Hormone Receptor
Authors: Carmen Pazos-Moura, E. Dale Abel, Mary-Ellen Boers, Egberto Moura, Thomas G. Hampton, Jufeng Wang, James P. Morgan, Fredric E. Wondisford
Journal: Circulation Research (2000)

Abstract —Thyroid hormone deficiency has profound effects on the cardiovascular system, resulting in decreased cardiac contractility, adrenergic responsiveness, and vascular volume and increased peripheral vascular resistance. To determine the importance of direct cardiac effects in the genesis of hypothyroid cardiac dysfunction, the cardiac myocyte was specifically targeted with a mutant thyroid hormone receptor (TR)-β (Δ337T-TR-β 1 ) driven by the α-myosin heavy chain (α-MHC) gene promoter. As a control in these experiments, a wild-type (Wt) TR-β 1 was also targeted to the heart by using the same promoter. Transgenic mice expressing the mutant TR displayed an mRNA expression pattern consistent with cardiac hypothyroidism, even though their peripheral thyroid hormone levels were normal. When these animals were rendered hypothyroid or thyrotoxic, mRNA expression of MHC isoforms remained unchanged in the hearts of the Δ337T transgenic animals, in contrast to Wt controls or transgenic animals expressing Wt TR-β 1 , which exhibited the expected changes in steady-state MHC mRNA levels. Studies in Langendorff heart preparations from mutant TR-β 1 transgenic animals revealed evidence of heart failure with a significant reduction in +dP/dT, −dP/dT, and force-frequency responses compared with values in Wt controls and transgenic mice overexpressing the Wt TR-β 1 . In contrast, in vivo measures of cardiac performance were similar between Wt and mutant animals, indicating that the diminished performance of the mutant transgenic heart in vitro was compensated for by other mechanisms in vivo. This is the first demonstration indicating that isolated cardiac hypothyroidism causes cardiac dysfunction in the absence of changes in the adrenergic or peripheral vascular system.