tbuckley/cabot-search huggingface dataset:
Biogenic Amines and the Secretion of Parathyroid Hormone and Calcitonin*
Authors: HUNTER HEATH
Journal: Endocrine Reviews (1980)

Ionic and nonionic control of parathyroid hormone and calcitonin secretion There is general agreement that the plasma concentration of calcium is the dominant regulator of parathyroid hormone (PTH) secretion (1–4) and probably also of calcitonin (CT) release (5, 6). Calcium stimulates CT secretion but inhibits PTH release; hypocalcemia has the opposite effects. Under certain conditions, other divalent cations, especially magnesium, can influence PTH and CT secretion in a fashion parallel to that of calcium, but there is little evidence that these relationships are of importance within the physiological range (3, 4). Normal secretion of PTH does, however, require the presence of magnesium (8, 9). Absence of the chloride and hydroxyl anions impairs PTH release in vitro (10), but it seems unlikely that levels of those anions have a specific regulatory function in calcium homeostasis. Phosphate infusion stimulates PTH secretion only by lowering plasma ionic calcium levels (2, 11), and an early report (12) that phosphate raised plasma immunoreactive CT (iCT) concentrations has not been verified (13).
Gastrointestinal Disorders: A Pathophysiologic Approach
Authors: Phillip M. Berman
Journal: JAMA (1990)

Gastrointestinal Disorders: A Pathophysiologic Approach is meant to teach rather than merely inform. The fourth edition provides a thorough update of the pathogenesis and clinical presentation of gastrointestinal problems.  The author provides recent advances in the mechanism of gastric acid secretion with a clear explanation of the hydrogen/potassium adenosinetriphosphatase proton pump and its inhibitor omeprazole. He compares and contrasts the four available H 2 -receptor antagonists. There is a review of pancreatic enzyme secretion, toxic and drug-induced hepatitis, and the formation of cholesterol gallstones.  The format of this 400 + -page, singleauthored, paperback monograph, with its liberal use of tables, figures, and graphs to highlight the crisp, carefully edited text, makes it a valuable tool for medical students, house officers, GI fellows, and those who teach gastroenterology. The chapter discussing the differential diagnosis and evaluation of a patient with jaundice is particularly well done. Case presentations are used to develop the
Genome-Wide Association Identifies Regulatory Loci Associated with Distinct Local Histogram Emphysema Patterns
Authors: Peter J. Castaldi, Michael H. Cho, Raúl San José Estépar, Merry-Lynn N. McDonald, Nan Laird, Terri H. Beaty, George Washko, James D. Crapo, Edwin K. Silverman
Journal: American Journal of Respiratory and Critical Care Medicine (2014)

Emphysema is a heritable trait that occurs in smokers with and without chronic obstructive pulmonary disease. Emphysema occurs in distinct pathologic patterns, but the genetic determinants of these patterns are unknown.To identify genetic loci associated with distinct patterns of emphysema in smokers and investigate the regulatory function of these loci.Quantitative measures of distinct emphysema patterns were generated from computed tomography scans from smokers in the COPDGene Study using the local histogram emphysema quantification method. Genome-wide association studies (GWAS) were performed in 9,614 subjects for five emphysema patterns, and the results were referenced against enhancer and DNase I hypersensitive regions from ENCODE and Roadmap Epigenomics cell lines.Genome-wide significant associations were identified for seven loci. Two are novel associations (top single-nucleotide polymorphism rs379123 in MYO1D and rs9590614 in VMA8) located within genes that function in cell-cell signaling and cell migration, and five are in loci previously associated with chronic obstructive pulmonary disease susceptibility (HHIP, IREB2/CHRNA3, CYP2A6/ADCK, TGFB2, and MMP12). Five of these seven loci lay within enhancer or DNase I hypersensitivity regions in lung fibroblasts or small airway epithelial cells, respectively. Enhancer enrichment analysis for top GWAS associations (single-nucleotide polymorphisms associated at P < 5 × 10(-6)) identified multiple cell lines with significant enhancer enrichment among top GWAS loci, including lung fibroblasts.This study demonstrates for the first time genetic associations with distinct patterns of pulmonary emphysema quantified by computed tomography scan. Enhancer regions are significantly enriched among these GWAS results, with pulmonary fibroblasts among the cell types showing the strongest enrichment.
Embryonic Lethality after Combined Inactivation of<i>Fancd2</i>and<i>Mlh1</i>in Mice
Authors: Henri J. van de Vrugt, Laura Eaton, Amy Hanlon Newell, Mushen Al-Dhalimy, R. Michael Liskay, Susan B. Olson, Markus Grompe
Journal: Cancer Research (2009)

Abstract DNA repair defects are frequently encountered in human cancers. These defects are utilized by traditional therapeutics but also offer novel cancer treatment strategies based on synthetic lethality. To determine the consequences of combined Fanconi anemia (FA) and mismatch repair pathway inactivation, defects in Fancd2 and Mlh1 were combined in one mouse model. Fancd2/Mlh1 double-mutant embryos displayed growth retardation resulting in embryonic lethality and significant underrepresentation among progeny. Additional inactivation of Trp53 failed to improve the survival of Fancd2/Mlh1–deficient embryos. Mouse fibroblasts were obtained and challenged with cross-linking agents. Fancd2-deficient cells displayed the FA-characteristic growth inhibition after mitomycin C (MMC) exposure. In primary fibroblasts, the absence of Mlh1 did not greatly affect the MMC sensitivity of Fancd2-deficient and Fancd2-proficient cells. However, in Trp53 mutant immortalized fibroblasts, Mlh1 deficiency reduced the growth-inhibiting effect of MMC in Fancd2 mutant and complemented cells. Similar data were obtained using psoralen/UVA, signifying that MLH1 influences the cellular sensitivity to DNA interstrand cross-links. Next, the effect of MLH1 deficiency on the formation of chromosomal aberrations in response to cross-linking agents was determined. Surprisingly, Mlh1 mutant fibroblasts displayed a modest but noticeable decrease in induced chromosomal breakage and interchange frequencies, suggesting that MLH1 promotes interstrand cross-link repair catastrophe. In conclusion, the combined inactivation of Fancd2 and Mlh1 did not result in synthetic lethality at the cellular level. Although the absence of Fancd2 sensitized Mlh1/Trp53 mutant fibroblasts to MMC, the differential survival of primary and immortalized fibroblasts advocates against systemic inactivation of FANCD2 to enhance treatment of MLH1-deficient tumors. [Cancer Res 2009;69(24):9431–8]
Changes in Adiposity Associated With Pregnancy
Authors: Holly L. Thacker
Journal: JAMA (1994)

<h3>To the Editor.</h3> —Dr Smith and colleagues<sup>1</sup>conclude that there is an association between a first pregnancy and adverse adiposity changes independent of demographic and behavioral factors. This conclusion is flawed. One of the most important behavioral factors related to postpartum weight changes that was not discussed in this study or the accompanying Editorial<sup>2</sup>is lactation. The weight gain in pregnancy not only is related to fetal development, but also is in preparation for prolonged lactation. The benefits of breast-feeding to infants are well recognized and physicians have been urged to be a source of breast-feeding support.<sup>3</sup>The benefits of breast-feeding to the woman herself, including reduction in the risk of premenopausal breast cancer, are increasingly being recognized.<sup>4</sup>It is likely that the adverse weight consequences of a first pregnancy relate to inadequate lactation in the majority of women. The authors of this article noted that
Most patients depressed by cancer do not need drugs
Authors: U. S Schuler
Journal: BMJ (2002)

EDITOR—In the ABC of psychological medicine Peveler et al discuss depression in medical patients.1 As a haematologist I often have to respond to depressive reactions in patients with malignant disease who are confronted with a poor prognosis and difficult decisions about treatment. Some degree of this reactive demoralisation is normal and has to be acknowledged. It is psychological in nature and different …
Restoration of normal coronary flow after no-reflow phenomenon does not improve post-procedural myocardial infarction in patients without ST-segment elevation myocardial infarction
Authors: Cem Barcin, Ali E. Denktas, Ryan J. Lennon, LaVon Hammes, Amir Lerman, David R. Holmes, Kirk N. Garratt
Journal: Journal of the American College of Cardiology (2003)
Identifying relevant studies for systematic reviews
Authors: M. Clarke, L. Greaves
Journal: BMJ (1995)

5 SD for HbAj measured by electrophoresis (mean 6-30% (SD 0 75%)) is 10-05%, representing an increment of 59 5%.It might be expected that more patients would have an increment of > 35-3% by one test than had an increment of > 59-3% by a second test when the two tests are so similar (that is, the main part of HbAl is HbA,c).
Rescue Obligations and Collective Approaches: Complexities in Genomics
Authors: Angela Fenwick, Sandi Dheensa, Gillian Crawford, Shiri Shkedi-Rafid, Anneke Lucassen
Journal: The American Journal of Bioethics (2015)

We agree with Garrett (2015) that too hasty an application of a duty to rescue in a wide variety of cases should be questioned and that the “purported duty to regularly return incidental findings i...
Treatment of Emphysema
Authors: Harold A. Lyons
Journal: JAMA (1965)

Obstructive emphysema is an increasing medical problem which challenges the physician of the present era. More than 14 million persons in the United States are affected with some form of disease obstructing the airway. Although improved recognition of obstructive emphysema and fewer errors in its diagnosis have come about within the past ten years, full appreciation of basic principles of treatment is often wanting.  In the United States, deaths from chronic pulmonary emphysema have more than quadrupled in the last ten years. Approximately 5 deaths per 100,000 persons are due to obstructive emphysema. Even more apparent is the morbidity due to the disease.  The greatest effort must be directed toward prevention and cure of this disease. Therapeutic measures should be instituted before serious complications result. The most adverse influence upon the prognosis of emphysema is the development of right-heart failure and secondary polycythemia. 1 Every effort of therapy, therefore, should
Recognition of Anterior Wall Infarction in Patients with Left Ventricular Hypertrophy
Authors: PAUL G. HUGENHOLTZ, THOMAS J. RYAN, THOMAS WOERNER, HAROLD D. LEVINE
Journal: Circulation (1963)

Horizontal plane projections of vectorcardiograms registered by the Frank lead system were analyzed in 36 patients with left ventricular hypertrophy and in 24 with left ventricular hypertrophy and associated anterior wall infarction. All were studied at autopsy. The 0.01-, 0.02-, 0.03-second, and maximum QRS vectors were compared with similar measurements in 60 control subjects previously reported. New criteria for the vector-cardiographic diagnosis of left ventricular hypertrophy have been outlined. Close agreement with earlier reported groups of patients with anteroseptal and anterolateral infarction was found, and findings by others in patients with left ventricular hypertrophy were confirmed. The direction of the 0.02-second QRS vector allowed the separation of the infarct group from the left ventricular hypertrophy group and from the normal, whereas the direction of the 0.03-second and maximum QRS vectors separated left ventricular hypertrophy from the normal. The magnitude of the maximum QRS vector is another highly reliable indicator of left ventricular hypertrophy and also serves to separate this group from those with associated anterior wall infarct. The influence of associated right ventricular hypertrophy or posterobasal infarction on left ventricular hypertrophy has been discussed. The accuracy of this technic of vectorcardiographic differentiation between left ventricular hypertrophy on the one hand and left ventricular hypertrophy with anterior infarction on the other in every instance was confirmed at autopsy. In all 12 patients whose electrocardiograms presented the dilemma of QS or rS complexes in leads V 1 to V 3 of the standard precordial electrocardiogram, the vectorcardiographic diagnosis was confirmed at autopsy. The Frank vectorcardiogram is a sensitive and reliable method to recognize left ventricular hypertrophy and may prove to be a useful adjunct to the ordinary electrocardiogram in cases where the electrocardiographic diagnosis is questionable.
GENDER RELATED DIFFERENCES IN PATIENTS UNDERGOING TRANSFEMORAL AORTIC VALVE IMPLANTATION FOR SEVERE AORTIC STENOSIS
Authors: Ofer Havakuk, Arie Steinvil, Ariel Finkelstein, Yigal Abramowitz, Gad Keren, Shmuel Banai
Journal: Journal of the American College of Cardiology (2013)
Circulating eosinophil/basophil progenitors and nasal mucosal cytokines in seasonal allergic rhinitis
Authors: M Linden, C Svensson, M Andersson, L Greiff, E Andersson, JA Denburg, CGA Persson
Journal: Allergy (1999)

Accumulation of eosinophils in the airways is characteristic of allergic rhinitis and asthma. The tissue eosinophilia may involve both recruitment of mature eosinophils and proliferation of their progenitors. This study examines mature eosinophils (nasal and circulating), their circulating progenitors, and a potential role of granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) in stimulating these progenitors. Twelve subjects with a history of seasonal allergic rhinitis and positive skin prick test for birch pollen were studied during four periods: shortly before, in the early and intense phase, at the end, and well after the Swedish birch‐pollen season. Nasal mucosal and circulating eosinophils were examined in both nasal brushings and peripheral blood samples. Eosinophil/basophil progenitors were determined by counting colony‐forming units in nonadherent mononuclear blood‐cell cultures in methylcellulose at 14 days. The nasal mucosal cytokines GM‐CSF, interleukin (IL)‐1β, IL‐3, IL‐5, IL‐6, IL‐8, and RANTES were analyzed (ELISA) in nasal lavage (NAL) fluids. All patients developed severe symptoms of rhinitis at the height of the season, with increased numbers of eosinophils in the nasal mucosa ( P &lt;0.05) and in the circulation ( P &lt;0.05). At this time point, the number of circulating progenitors ( P &lt;0.05) and the NAL fluid level of GM‐CSF ( P &lt;0.05) were also increased. In contrast, there was no change in the NAL fluid levels of IL‐1β, IL‐3, IL‐6, or IL‐8. Neither IL‐5 nor RANTES could be detected in any of the NAL fluids. At the end of or after the season, there was no increase in nasal eosinophils or circulating eosinophils or progenitors ( P &gt;0.05). Ex vivo addition of GM‐CSF (10–100 U) increased the number of blood progenitors grown before ( P &lt;0.01) and after ( P &lt;0.05) the season, compared with during the season. The in vitro GM‐CSF responsiveness of progenitors may be related to whether or not these already have been stimulated endogenously by GM‐CSF. Taken together, our data thus suggest that GM‐CSF may play a role in vivo to increase production of eosinophilic progenitors in allergic airway disease.
Regulation of early cholesterol biosynthesis in rat liver: Effects of sterols, bile acids, lovastatin, and BM 15.766 on 3-hydroxy-3-methylglutaryl coenzyme A synthase and acetoacetyl coenzyme A thiolase activities
Authors: Akira Honda, Gerald Salen, Lien B. Nguyen, Guorong Xu, Stephen G. Tint, Ashok K. Batta, Sarah Shefer
Journal: Hepatology (1998)

Cytosolic 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) synthase catalyzes the formation of HMG-CoA, the substrate for the rate-controlling enzyme in the cholesterol biosynthetic pathway. To explore the regulation in liver, we developed a new, accurate, and reliable reversed-phase ion-pair chromatographic assay that uses nonradioactive substrates and n -propionyl coenzyme A as an internal recovery standard. The hepatic activities were measured in rats treated with cholesterol, sitosterol, cholic acid, deoxycholic acid, ursodeoxycholic acid, cholestyramine, bile fistula, lovastatin, and BM 15.766, an inhibitor of 7-dehydrocholesterol Δ 7 -reductase, and were compared with microsomal HMG-CoA reductase and cytosolic acetoacetyl coenzyme A (AcAc-CoA) thiolase activities. HMG-CoA synthase activity was effectively suppressed in synchrony with HMG-CoA reductase activity by treatments with cholesterol (−41%, P &lt; .05), cholic acid (−72%, P &lt; .005), and deoxycholic acid (−62%, P &lt; .05). However, ursodeoxycholic acid increased activity 84% ( P &lt; .05) and intravenous sitosterol did not change activity. AcAc-CoA thiolase activities also paralleled HMG-CoA reductase and HMG-CoA synthase activities, but differences were not statistically significant. In contrast to inhibition, up-regulation of hepatic HMG-CoA synthase activities by cholestyramine, bile fistula, and lovastatin was much less than HMG-CoA reductase activities. In addition, BM 15.766 did not stimulate synthase activity, whereas lovastatin increased activity 2.4-fold. Thus, hepatic HMG-CoA synthase activity was regulated coordinately with HMG-CoA reductase, and responded more forcefully to regulatory stimuli than acetoacetyl-CoA thiolase activity but usually less than HMG-CoA reductase.
Transfusion-associated TT virus infection and its relationship to liver disease
Authors: Akihiro Matsumoto, Anthony E. Yeo, J. Wai Shih, Eiji Tanaka, Kendo Kiyosawa, Harvey J. Alter
Journal: Hepatology (1999)

TT virus (TTV) has been proposed as the causative agent of non-A to E hepatitis. We studied the association between TTV viremia and biochemical evidence of hepatitis in blood donors and prospectively-followed patients. TTV was found in 7.5% of 402 donors and in 11.0% of 347 patients before transfusion. The rate of new TTV infections was 4.7% in 127 nontransfused, and 26.4% in 182 transfused patients (P <.0001). The risk of infection increased with the number of units transfused (P <.0001). The rate of new TTV infections in 13 patients with non-A to E hepatitis (23.2%) was almost identical to the rate in 124 patients who were transfused, but did not develop hepatitis (21.8%). Of 45 patients with acute hepatitis C, 40.0% were simultaneously infected with TTV. TTV did not worsen the biochemical severity (mean ALT: 537 in TTV+; 550 in TTV-) or persistence of hepatitis C. In non-A to E cases, the mean ALT was 182 in those TTV-positive and 302 in TTV-negatives. No consistent relationship between alanine transaminase level and TTV DNA level was observed in 4 patients with long-term, sequential samples. Of 21 viremic subjects, 67% cleared TTV within 5 years (38% in 1 year); 33% were viremic throughout follow-up extending to 22 years. We conclude that TTV is a very common, often persistent infection that is transmitted by transfusion and by undefined nosocomial routes. We found no association between TTV and non-A to E hepatitis and no effect of TTV on the severity or duration of coexistent hepatitis C. TTV may not be a primary hepatitis virus.
Confidential inquiry into quality of care before admission to intensive care
Authors: P. McQuillan, S. Pilkington, A. Allan, B. Taylor, A. Short, G. Morgan, M. Nielsen, D. Barrett, G. Smith
Journal: BMJ (1998)

To examine the prevalence, nature, causes, and consequences of suboptimal care before admission to intensive care units, and to suggest possible solutions.Prospective confidential inquiry on the basis of structured interviews and questionnaires.A large district general hospital and a teaching hospital.A cohort of 100 consecutive adult emergency admissions, 50 in each centre.Opinions of two external assessors on quality of care especially recognition, investigation, monitoring, and management of abnormalities of airway, breathing, and circulation, and oxygen therapy and monitoring.Assessors agreed that 20 patients were well managed (group 1) and 54 patients received suboptimal care (group 2). Assessors disagreed on quality of management of 26 patients (group 3). The casemix and severity of illness, defined by the acute physiology and chronic health evaluation (APACHE II) score, were similar between centres and the three groups. In groups 1, 2, and 3 intensive care mortalities were 5 (25%), 26 (48%), and 6 (23%) respectively (P=0.04) (group 1 versus group 2, P=0.07). Hospital mortalities were 7 (35%), 30 (56%), and 8 (31%) (P=0.07) and standardised hospital mortality ratios (95% confidence intervals) were 1.23 (0.49 to 2.54), 1.4 (0.94 to 2.0), and 1.26 (0.54 to 2.48) respectively. Admission to intensive care was considered late in 37 (69%) patients in group 2. Overall, a minimum of 4.5% and a maximum of 41% of admissions were considered potentially avoidable. Suboptimal care contributed to morbidity or mortality in most instances. The main causes of suboptimal care were failure of organisation, lack of knowledge, failure to appreciate clinical urgency, lack of supervision, and failure to seek advice.The management of airway, breathing, and circulation, and oxygen therapy and monitoring in severely ill patients before admission to intensive care units may frequently be suboptimal. Major consequences may include increased morbidity and mortality and requirement for intensive care. Possible solutions include improved teaching, establishment of medical emergency teams, and widespread debate on the structure and process of acute care.
An Aspirin Tablet and a Gastric Ulcer
Authors: D J Levy
Journal: New England Journal of Medicine (2000)

Figure 1. A 76-year-old woman had iron-deficiency anemia, a hematocrit of 24 percent, and a positive test for occult blood in stool. For several years, she had been taking 400 mg of etodolac twice a day for rheumatoid arthritis; one tablet of enteric-coated, regular-strength aspirin a day; and 1 mg of warfarin sodium a day for severe peripheral vascular disease. Her international normalized ratio was 1.15. After receiving a transfusion, she underwent upper gastrointestinal endoscopy, which revealed an aspirin tablet, with the enteric coating still intact, within an ulcer of the gastric antrum. The tablet was removed with a forceps. . . .
Comparative Assessment of Air Pollution–Related Health Risks in Houston
Authors: Ken Sexton, Stephen H. Linder, Dritana Marko, Heidi Bethel, Philip J. Lupo
Journal: Environmental Health Perspectives (2007)

Airborne emissions from numerous point, area, and mobile sources, along with stagnant meteorologic conditions, contribute to frequent episodes of elevated air pollution in Houston, Texas. To address this problem, decision makers must set priorities among thousands of individual air pollutants as they formulate effective and efficient mitigation strategies.Our aim was to compare and rank relative health risks of 179 air pollutants in Houston using an evidence-based approach supplemented by the expert judgment of a panel of academic scientists.Annual-average ambient concentrations by census tract were estimated from the U.S. Environmental Protection Agency's National-scale Air Toxics Assessment and augmented with measured levels from the Houston monitoring network. Each substance was assigned to one of five risk categories (definite, probable, possible, unlikely, uncertain) based on how measured or monitored concentrations translated into comparative risk estimates. We used established unit risk estimates for carcinogens and/or chronic reference values for noncarcinogens to set thresholds for each category. Assignment to an initial risk category was adjusted, as necessary, based on expert judgment about the quality and quantity of information available.Of the 179 substances examined, 12 (6.7%) were deemed definite risks, 9 (5.0%) probable risks, 24 (13.4%) possible risks, 16 (8.9%) unlikely risks, and 118 (65.9%) uncertain risks.Risk-based priority setting is an important step in the development of cost-effective solutions to Houston's air pollution problem.