tbuckley/cabot-search huggingface dataset:
Sedation in allergic rhinitis is caused by the condition and not by antihistamine treatment
Authors: J. Spaeth, L. Klimek, R. Mösges
Journal: Allergy (1996)

Sedation is regarded as a common side‐effect of most H 1 ‐antihistamines. This view must be accepted. yet can hardly be assessed under treatment of allergic disorders. Since central sedative potency is hard to evaluate, different methods of measurement have been introduced in the four phases of clinical investigation. While tests of high complexity in early trials can detect true central effects, they seem to have the disadvantage of not taking into consideration the important interactions of drugs with the disorder. Therefore, we used a visual analog scale (VAS) as an instrument to demonstrate sedative effects in five clinical studies carried out between 1989 and 1994 with a total number of 1070 patients. Thereby, we could assess the result of the different components of the central interaction. In 1989, in a double‐blind, placebo‐controlled trial, we could show that the vigilance of patients suffering from seasonal allergic rhinitis increased significantly more under treatment with an antihistamine (mizolastine) than under placebo. From 1992 until 1994, we compared azelastine nasal spray either by the double‐dummy technique with oral antihistamines (cetirizine, loratadine, and astemizole) or by the double‐dummy or placebo‐controlled design with monotherapy or combined therapy with azelastine tablets. A marked or statistically significant improvement of vigilance was found for all compounds (loratadine: P &lt; 0.0001; cetirizine: P &lt; 0.0254; and azelastine nasal spray: P &lt; 0.1409 to P &lt; 0.0001). Even when taking azelastine as oral application, patients, in spite of the warning, reported a similar increase in vigilance ( P &lt; 0.2628 to P &lt; 0.0001). Finally, we assessed the range of physiologic vigilance using the same VAS in healthy volunteers. In conclusion, we could prove that in all trials the baseline values of vigilance of untreated symptomatic patients were far below physiologic condition and improved under treatment to the upper range of healthy persons. Therefore, any sedative properties of modern H 1 ‐antihistamines should not limit their therapeutic use. since the truly threatening sedation results from the disorder itself.
The Many Faces of Emphysema
Authors: Sol Katz
Journal: JAMA (1968)

<h3>To the Editor:—</h3> The question is pertinent and reflects our inability to relate morphologic and physiologic alterations to specific disease categories based on certain clinical presentations in the absence of a well-defined etiology. The clinical expressions of chronic bronchitis and emphysema may overlap and indeed both conditions frequently coexist. Furthermore, other diseases may have similar clinical features requiring their exclusion, thereby further compounding the nosologic dilemma. Chronic bronchitis and emphysema are characterized by airway obstruction and cannot be differentiated by tests measuring ventilatory function. Chronic bronchitis is usually defined on the basis of clinical features of chronic, recurrent cough with excessive mucus production. Pulmonary emphysema is best defined by certain anatomical alterations in the distal air spaces rather than on clinical, radiological, or physiological abnormalities. Immediately, the limitations of these definitions becomes apparent—the nonspecificity of the clinical findings in chronic bronchitis and the clinical uselessness of a definition dependent on
Development and validation of a questionnaire to evaluate patient satisfaction with diabetes disease management.
Authors: L E Paddock, J Veloski, M L Chatterton, F O Gevirtz, D B Nash
Journal: Diabetes Care (2000)

OBJECTIVE: To develop a reliable and valid questionnaire to measure patient satisfaction with diabetes disease management programs. RESEARCH DESIGN AND METHODS: Questions related to structure, process, and outcomes were categorized into 14 domains defining the essential elements of diabetes disease management. Health professionals confirmed the content validity. Face validity was established by a patient focus group. The questionnaire was mailed to 711 patients with diabetes who participated in a disease management program. To reduce the number of questionnaire items, a principal components analysis was performed using a varimax rotation. The Scree test was used to select significant components. To further assess reliability and validity; Cronbach's alpha and product-moment correlations were calculated for components having &amp;gt; or =3 items with loadings &amp;gt;0.50. RESULTS: The validated 73-item mailed satisfaction survey had a 34.1% response rate. Principal components analysis yielded 13 components with eigenvalues &amp;gt; 1.0. The Scree test proposed a 6-component solution (39 items), which explained 59% of the total variation. Internal consistency reliabilities computed for the first 6 components (alpha = 0.79-0.95) were acceptable. CONCLUSIONS: The final questionnaire, the Diabetes Management Evaluation Tool (DMET), was designed to assess patient satisfaction with diabetes disease management programs. Although more extensive testing of the questionnaire is appropriate, preliminary reliability and validity of the DMET has been demonstrated.
Validation of fan beam dual energy<i>x</i>ray absorptiometry for body composition assessment in adults aged 18–45 years
Authors: J Norcross, M D Van Loan
Journal: British Journal of Sports Medicine (2004)

Background: Pencil beam dual energy x ray absorptiometry (DXA) has been shown to provide valid estimates of body fat (%BF), but DXA fan beam technology has not been adequately tested to determine its validity. Objective: To compare %BF estimated from fan beam DXA with %BF determined using two and three compartment (2C, 3C) models. Methods: Men (n = 25) and women (n = 31), aged 18–41 years, participated in the study. Body density, from hydrostatic weighing, was used in the 2C estimate of %BF; DXA was used to determine bone mineral content (BMC) for the 3C estimate of %BF calculated using body density and BMC (3C BMC ). DXA was also used to determine %BF. Analysis of variance was used to test for significant differences in %BF between sexes and among methods. Results: Women were significantly shorter, weighed less, had less fat free mass, and a higher %BF than men. No significant differences were found among methods (2C, 3C BMC , DXA) for determination of %BF in either sex. Although not significant, Bland-Altman plots showed that DXA gave higher values for %BF than the 2C and 3C BMC methods. Conclusion: DXA determination of %BF was not different from that of the 2C and 3C BMC models in this group of young adults. However, to validate fan beam DXA fully as a method for body composition assessment in a wide range of individuals and populations, comparisons are needed that use a 4C model with a measure of total body water and BMC.
A lasting influence: Listen to the patient
Authors: R M. Pitkin
Journal: BMJ (1998)

It was about 30 years ago, at the beginning of what came to be called “fetal medicine,” that I first met Mrs Peterson. She was early in her fifth pregnancy and had written to the referral hospital where I worked, recounting a history of progressively severe rhesus isoimmunisation with her last two pregnancies, resulting in fetal deaths at mid-gestation. Having read about the new techniques of amniotic fluid analysis and direct fetal transfusion, she wondered if they could help her. The very detailed and specific information she provided (which I would come to learn was one of Mrs Peterson's essential characteristics) indicated that the only hope lay with fetal transfusion.

We carried on a dialogue by letter and telephone, consisting mainly of Mrs Peterson asking question after …
The natural history of acute and chronic thromboembolic disease: the search for the missing link
Authors: P.F. Fedullo, L.J. Rubin, K.M. Kerr, W.R. Auger, R.N. Channick
Journal: European Respiratory Journal (2000)

Thiopurine drugs such as 6-mercaptopurine (6-MP) and 6-thioguanine (6-TG) are used to treat acute lymphoblastic leukemia of childhood. To test the hypothesis that variation in the expression of genes within the "thiopurine pathway" might influence 6-MP and 6-TG sensitivity, we generated basal gene expression profiles and IC<sub>50</sub> values for both of these thiopurine drugs using a model system consisting of 194 Human Variation Panel lymphoblastoid cell lines. Association analysis showed that thiopurine <i>S</i>-methyltransferase, ecto-5′-nucleotidase (NT5E), and multidrug resistance protein 4 (ABCC4) expression were correlated with thiopurine cytotoxicity. Those observations suggested the possible existence of a "thiopurine cellular circulation" involving nucleotide efflux by ABCC4, hydrolysis of thiopurine nucleotide monophosphates outside of the cell by NT5E, and subsequent transport of thiopurine nucleosides back into the cell by nucleoside transporters. The existence of this cellular circulation was confirmed by a series of functional experiments performed with cultured cells stably or transiently transfected with ABCC4 and/or NT5E. Because of the central role of NT5E in this cellular circulation, the <i>NT5E</i> gene was resequenced using 287 DNA samples from three ethnic groups, with the identification of 68 single nucleotide polymorphisms (SNPs), 46 of which were novel. Several SNPs in the 5′-flanking region of <i>NT5E</i> were highly correlated with expression, rs9450278 having the lowest <i>p</i> value (<i>p</i> = 2.4 × 10<sup>−10</sup>, <i>R</i> = −0.376). The thiopurine cellular circulation and genetic polymorphisms for genes encoding the proteins involved should be incorporated into future studies of thiopurine drug therapy and effect.
Regulation of Acetylation of Histone Deacetylase 2 by p300/CBP-Associated Factor/Histone Deacetylase 5 in the Development of Cardiac Hypertrophy
Authors: Gwang Hyeon Eom, Yoon Seok Nam, Jae Gyun Oh, Nakwon Choe, Hyun-Ki Min, Eun-Kyung Yoo, Gaeun Kang, Vu Hong Nguyen, Jung-Joon Min, Jong-Keun Kim, In-Kyu Lee, Rhonda Bassel-Duby, Eric N. Olson, Woo Jin Park, Hyun Kook
Journal: Circulation Research (2014)

Histone deacetylases (HDACs) are closely involved in cardiac reprogramming. Although the functional roles of class I and class IIa HDACs are well established, the significance of interclass crosstalk in the development of cardiac hypertrophy remains unclear.Recently, we suggested that casein kinase 2α1-dependent phosphorylation of HDAC2 leads to enzymatic activation, which in turn induces cardiac hypertrophy. Here we report an alternative post-translational activation mechanism of HDAC2 that involves acetylation of HDAC2 mediated by p300/CBP-associated factor/HDAC5.Hdac2 was acetylated in response to hypertrophic stresses in both cardiomyocytes and a mouse model. Acetylation was reduced by a histone acetyltransferase inhibitor but was increased by a nonspecific HDAC inhibitor. The enzymatic activity of Hdac2 was positively correlated with its acetylation status. p300/CBP-associated factor bound to Hdac2 and induced acetylation. The HDAC2 K75 residue was responsible for hypertrophic stress-induced acetylation. The acetylation-resistant Hdac2 K75R showed a significant decrease in phosphorylation on S394, which led to the loss of intrinsic activity. Hdac5, one of class IIa HDACs, directly deacetylated Hdac2. Acetylation of Hdac2 was increased in Hdac5-null mice. When an acetylation-mimicking mutant of Hdac2 was infected into cardiomyocytes, the antihypertrophic effect of either nuclear tethering of Hdac5 with leptomycin B or Hdac5 overexpression was reduced.Taken together, our results suggest a novel mechanism by which the balance of HDAC2 acetylation is regulated by p300/CBP-associated factor and HDAC5 in the development of cardiac hypertrophy.
Thrombolysis for acute stroke
Authors: R. von Kummer
Journal: JAMA (1996)

To the Editor.  —We appreciate the thoughtful Editorial of Dr Fisher and colleagues 1 on ECASS. 2 Their question, why experienced investigators misinterpreted so many initial CT scans, although provocative, addresses an important aspect of that trial.  The ECASS protocol defined clinical and CT inclusion and exclusion criteria to be checked by the local investigators of 75 European study centers and stated that a panel of 3 independent neuroradiologists will assess all CT scans centrally. It will function as final arbiter. They will double-check and identify eventual exclusion criteria as defined in 3.2 and assess intracranial hemorrhage as defined in Appendix 2.  Local monitors gathered all CT scans for submission to the chairman of the CT-Scan Reading Panel who provided the other two members with copies. The members individually and consecutively evaluated all CT scans of the study blinded to any clinical information. The study protocol did not blind their
Effect of Mutational Inactivation of Tyrosine Kinase Activity on BCR/ABL-Induced Abnormalities in Cell Growth and Adhesion in Human Hematopoietic Progenitors
Authors: Pandurangan Ramaraj, Harjeet Singh, Ning Niu, Su Chu, Melissa Holtz, Jiing Kuan Yee, Ravi Bhatia
Journal: Cancer Research (2004)

Abstract Chronic myelogenous leukemia (CML) results from transformation of a primitive hematopoietic cell by the BCR/ABL gene. The specific BCR/ABL signaling mechanisms responsible for transformation of primitive human hematopoietic cells are not well defined. Previous studies have suggested that constitutively activated tyrosine kinase activity plays an important role for in abnormal proliferation of CML progenitors but has not clearly defined its role in abnormal adhesion and migration. We established a human progenitor model of CML by ectopic expression of BCR/ABL in normal CD34+ cells using retrovirus-mediated gene transfer. CD34+ cells expressing BCR/ABL demonstrated several features characteristic of primary CML progenitors including increased proliferation in committed and primitive progenitor culture, reduced adhesion to fibronectin, and reduced chemotaxis to stroma-derived factor-1α. We expressed a kinase-inactive BCR/ABL gene to directly investigate the role of kinase activity in abnormal progenitor function. Abnormalities in proliferation were completely reversed, whereas defects in adhesion and migration were significantly improved but not completely reversed in cells expressing a kinase-inactive BCR/ABL. Furthermore, the BCR/ABL kinase inhibitor imatinib mesylate markedly inhibited proliferation of BCR/ABL-expressing progenitors but did not fully correct the adhesion and migration defects. Expression of BCR/ABL genes with deletions of either the COOH-terminal actin binding or proline-rich domains resulted in enhanced adhesion and chemotaxis compared with wild-type BCR/ABL but did not affect progenitor proliferation. We conclude that abnormal kinase activity is essential for abnormal proliferation and survival of CML progenitors but that abnormal adhesion and migration result from both kinase-dependent and -independent mechanisms.
Vaccine Vectors Derived from a Large Collection of Simian Adenoviruses Induce Potent Cellular Immunity Across Multiple Species
Authors: Stefano Colloca, Eleanor Barnes, Antonella Folgori, Virginia Ammendola, Stefania Capone, Agostino Cirillo, Loredana Siani, Mariarosaria Naddeo, Fabiana Grazioli, Maria Luisa Esposito, Maria Ambrosio, Angela Sparacino, Marta Bartiromo, Annalisa Meola, Kira Smith, Ayako Kurioka, Geraldine A. O’Hara, Katie J. Ewer, Nicholas Anagnostou, Carly Bliss, Adrian V. S. Hill, Cinzia Traboni, Paul Klenerman, Riccardo Cortese, Alfredo Nicosia
Journal: Science Translational Medicine (2012)

Simian adenoviruses screened from wild-derived candidates can prime T cell responses in man and may serve as new vaccine vector candidates.
Malpractice Claims Data as a Quality Improvement Tool
Authors: John E. Rolph
Journal: JAMA (1991)

<h3>Objective.</h3> —To evaluate the usefulness of malpractice claims data for identifying (1) physicians who are prone to negligent errors and (2) physician and hospital characteristics associated with particular kinds of errors. <h3>Design.</h3> —Retrospective review of physician malpractice claim records. <h3>Setting.</h3> —Large New Jersey physician malpractice insurer. <h3>Participants.</h3> —Physicians practicing obstetrics and gynecology, general surgery, anesthesiology, or radiology and covered by the insurance carrier for any portion of 1977 through 1989. <h3>Main Outcome Measures.</h3> —Claims were classified into 11 clinical error categories comprising three broad groups: patient management problems, technical performance problems, and staff coordination problems. Outcomes were expressed as per-physician frequency of claims due to negligence and proportion of claims associated with various types of errors. <h3>Results.</h3> —Using 5 years of claims history to predict long-term claims proneness was more accurate than chance alone by 57% in obstetrics and gynecology, 33% in general surgery, 11% in anesthesiology, and 15% in radiology. Cross-validated recursive partitioning showed that among physician characteristics, only specialty was predictive of physician error profiles. For physician claims arising in acute care hospitals, hospital size and location in addition to hospital services discriminated among different error profiles; the cross-validated accuracy of this method was 69% compared with 22% accuracy achieved by random prediction. <h3>Conclusion.</h3> —Use of physicians' malpractice claims histories to target individuals for education or sanctions is problematic because of the only modest predictive power of such claims histories. (<i>JAMA</i>. 1991;266:2093-2097)
Dynamic effects of carotid sinus baroreflex on ventriculoarterial coupling studied in anesthetized dogs.
Authors: T Kubota, J Alexander, R Itaya, K Todaka, M Sugimachi, K Sunagawa, Y Nose, A Takeshita
Journal: Circulation Research (1992)

We evaluated dynamic effects of the carotid sinus baroreflex on ventriculoarterial coupling. In seven anesthetized, vagotomized dogs, we bilaterally isolated carotid sinuses and randomly changed carotid sinus pressure while measuring aortic pressure, aortic flow, and left ventricular pressure. Estimating left ventricular end-systolic elastance (Ees) and effective arterial elastance (Ea) on a beat-to-beat basis, we determined transfer functions from the carotid sinus pressure to Ees (HEes) and from the carotid sinus pressure to Ea (HEa) over the frequency range spanning 0.002-0.25 Hz. Both HEes and HEa exhibited characteristics of a second-order low-pass filter. The gains of HEes and HEa were 0.085 +/- 0.065 (mean +/- SD) and 0.081 +/- 0.049 mm Hg/ml/mm Hg, respectively. There were no significant differences in natural frequencies (0.039 +/- 0.013 versus 0.039 +/- 0.007 Hz) or damping ratios (0.65 +/- 0.11 versus 0.64 +/- 0.24). The results indicated that the carotid sinus baroreflex dynamically altered Ees and Ea to the same extent in the process of stabilizing arterial pressure. Because the arterial system extracts maximal external work from a given heart when Ea equals Ees, the carotid sinus baroreflex appeared to be designed to regulate the ventricular and arterial properties to optimize the energy transmission from the left ventricle to the arterial system in anesthetized, vagotomized dogs.
Effects of Oral Contraceptive Use on the Renal and Systemic Vascular Response to Angiotensin II Infusion
Authors: Sofia B. Ahmed, Amrit K. Kang, Kevin D. Burns, Christopher R. J. Kennedy, Vesta Lai, Daniel C. Cattran, James W. Scholey, Judith A. Miller
Journal: Journal of the American Society of Nephrology (2004)

ABSTRACT. We have previously shown that users of oral contraceptive (OC) medications exhibit increased plasma levels of angiotensin II (Ang II) with only modest hemodynamic consequences, suggesting estrogen-mediated Ang II type 1 (AT<sub>1</sub>) receptor downregulation. Accordingly, in 10 women who were OC users and 10 women who, as OC nonusers, served as controls, all mean age 26 ± 1 yr, we examined the renal and peripheral hemodynamic response to graded Ang II infusion, plasma and urine cyclic guanosine monophosphate (cGMP) levels as a surrogate marker for AT<sub>1</sub> and/or AT<sub>2</sub> receptor-mediated activation of the nitric oxide pathway, and AT<sub>1</sub> receptor expression in skin biopsies. The OC nonusers were studied during the follicular and luteal phases of the menstrual cycle, whereas OC users were studied once during the 21-d medication phase. Subjects ingested a controlled sodium diet for 7 d before each study. Renal hemodynamic function was assessed using standard inulin and <i>p</i>-aminohippurate clearance techniques. AT<sub>1</sub> receptor mRNA levels in skin biopsy samples were assessed using a real-time PCR protocol. In response to graded Ang II infusion, OC users exhibited renal and peripheral hemodynamic responses that were augmented compared with those of OC nonusers, in conjunction with evidence of increased tissue AT<sub>1</sub> receptor expression. Plasma cGMP levels and 24-h urinary cGMP excretion did not differ. These data suggest that, contrary to our original hypothesis, OC use does not appear to be associated with AT<sub>1</sub> receptor downregulation. The factor protecting OC users from the hemodynamic impact of increased Ang II levels remains elusive.
Sex Hormone Levels and Risk of Cardiovascular Events in Postmenopausal Women
Authors: Kathryn M. Rexrode, JoAnn E. Manson, I-Min Lee, Paul M Ridker, Patrick M. Sluss, Nancy R. Cook, Julie E. Buring
Journal: Circulation (2003)

Despite diffuse effects of sex hormones on the cardiovascular system, few prospective studies have examined the relationship of plasma androgens and estrogens with risk of cardiovascular disease (CVD) in postmenopausal women.A nested case-control study was performed among women in the Women's Health Study. Two hundred women who developed CVD were matched 1:1 by age, smoking, and postmenopausal hormone therapy (HT) to controls who remained free of CVD. We measured testosterone, estradiol, and sex hormone binding globulin (SHBG) levels and calculated free androgen index (FAI), free estradiol index, and the FAI/free estradiol index ratio. Results were stratified by HT use. Among HT nonusers, cases had significantly higher androgen profiles (higher median FAI and lower SHBG levels) than controls. After adjustment for age, smoking, use of aspirin, vitamin E, and alcohol, family history of myocardial infarction, and physical activity, nonusers in the lowest SHBG quartile had an OR of 2.25 (95% CI, 1.03 to 4.91) for CVD, and there were significant trends across FAI quartiles (P for trend=0.03). Additional adjustment for body mass index, hypertension, diabetes, and elevated cholesterol eliminated associations with SHBG and FAI. Among women using HT, no significant differences in hormones or SHBG were observed among women who developed CVD and controls.Among HT nonusers, lower SHBG and higher FAI levels were noted among postmenopausal women who developed CVD events, but this was not independent of body mass index and other cardiovascular risk factors. Estradiol levels were not associated with risk of CVD in HT users or nonusers.
Aquatic Invertebrates: Model Systems for Study of Receptor Activation and Evolution of Receptor Proteins
Authors: H M Lenhoff, W Heagy
Journal: The Annual Review of Pharmacology and Toxicology (1977)

Since the spread of tobacco from the Americas hundreds of years ago, tobacco cigarettes and, more recently, alternative tobacco products have become global products of nicotine addiction. Within the evolving alternative tobacco product space, electronic ...Read More