tbuckley/cabot-search huggingface dataset:
Response of plasma atrial natriuretic factor to experimentally induced aortic and mitral regurgitation in dogs
Authors: T. Masuda, K. Satoh, K. Ando, T. Takamoto, F. Marumo
Journal: Cardiovascular Research (1991)

Study objective – The correlations between the plasma concentration of atrial natriuretic factor and right atrial or left atrial pressure were studied in experimentally induced aortic regurgitation and mitral regurgitation in dogs. Design – Aortic regurgitation was created by opening the tip of a basket wire catheter placed at the aortic annulus via the left ventricular wall, and terminated by pulling back the catheter. To create mitral regurgitation a basket catheter was inserted into the mitral annular position via a pulmonary vein. Regurgitation was induced by opening the tip of the catheter, and terminated promptly by closing it. Experimental material – Seven beagle dogs were prepared for the aortic regurgitation model and six for the mitral regurgitation model (weights 11.5 to 14.5 kg). Measurements and main results – The plasma concentration of atrial natriuretic factor was highly correlated with right atrial pressure (r = 0.78, SD = 0.07, n = 7) and left atrial pressure (r = 0.82, SD = 0.05, n = 7) in aortic regurgitation; and with right atrial pressure (r = 0.82, SD = 0.05, n = 6) and left atrial pressure (r = 0.84, SD = 0.05, n = 6) in mitral regurgitation. Further evaluation of the molecular forms of plasma atrial natriuretic factor revealed the α form in all 13 dogs and the γ form in two (one with aortic and the other with mitral regurgitation); no evidence of the β form was seen. Conclusions – Atrial natriuretic factor secretion responds rapidly to the circulatory changes caused by valvular incompetence.
Increased amyloidogenic processing of transgenic human APP in X11-like deficient mouse brain
Authors: Maho Kondo, Maki Shiono, Genzo Itoh, Norio Takei, Takahide Matsushima, Masahiro Maeda, Hidenori Taru, Saori Hata, Tohru Yamamoto, Yuhki Saito, Toshiharu Suzuki
Journal: Molecular Neurodegeneration (2010)

X11-family proteins, including X11, X11-like (X11L) and X11-like 2 (X11L2), bind to the cytoplasmic domain of amyloid β-protein precursor (APP) and regulate APP metabolism. Both X11 and X11L are expressed specifically in brain, while X11L2 is expressed ubiquitously. X11L is predominantly expressed in excitatory neurons, in contrast to X11, which is strongly expressed in inhibitory neurons. In vivo gene-knockout studies targeting X11, X11L, or both, and studies of X11 or X11L transgenic mice have reported that X11-family proteins suppress the amyloidogenic processing of endogenous mouse APP and ectopic human APP with one exception: knockout of X11, X11L or X11L2 has been found to suppress amyloidogenic metabolism in transgenic mice overexpressing the human Swedish mutant APP (APPswe) and the mutant human PS1, which lacks exon 9 (PS1dE9). Therefore, the data on X11-family protein function in transgenic human APP metabolism in vivo are inconsistent.To confirm the interaction of X11L with human APP ectopically expressed in mouse brain, we examined the amyloidogenic metabolism of human APP in two lines of human APP transgenic mice generated to also lack X11L. In agreement with previous reports from our lab and others, we found that the amyloidogenic metabolism of human APP increased in the absence of X11L.X11L appears to aid in the suppression of amyloidogenic processing of human APP in brain in vivo, as has been demonstrated by previous studies using several human APP transgenic lines with various genetic backgrounds. X11L appears to regulate human APP in a manner similar to that seen in endogenous mouse APP metabolism.
The influence of hydroxypropyl methylcellulose (HPMC) molecular weight, concentration and effect of food on in vivo erosion behavior of HPMC matrix tablets
Authors: Arun Kumar Jain, Erik Söderlind, Anna Viridén, Barbara Schug, Bertil Abrahamsson, Christian Knopke, Farhad Tajarobi, Henning Blume, Maria Anschütz, Anette Welinder, Sara Richardson, Stefan Nagel, Susanna Abrahmsén-Alami, Werner Weitschies
Journal: Journal of Controlled Release (2014)
Implantable Cardioverter Defibrillators in Primary and Secondary Prevention
Authors: Justin A. Ezekowitz, Paul W. Armstrong, Finlay A. McAlister
Journal: Annals of Internal Medicine (2003)

Background: Sudden cardiac death is common in persons with cardiovascular disease. Purpose: To assess the efficacy of implantable cardioverter defibrillators (ICDs) in persons at increased risk for sudden cardiac death. Data Sources: MEDLINE (19802002), EMBASE (19802002), Cochrane Controlled Clinical Trial Registry (2002, Volume 3), other databases, and conference proceedings. Primary study authors and device manufacturers were contacted, and bibliographies of relevant papers were hand searched. Study Selection: Randomized, controlled clinical trials evaluating ICDs versus usual care were selected. Data Extraction: Two reviewers extracted data independently. Data Synthesis: Eight trials were included in the final analysis (4909 patients, 1154 deaths). Compared with usual care (most commonly amiodarone therapy), ICDs significantly reduced sudden cardiac death (relative risk [RR], 0.43 [95% CI, 0.35 to 0.53]) and all-cause mortality (RR, 0.74 [CI, 0.67 to 0.82]). The included trials were divided a priori into two categories: secondary prevention (involving patients resuscitated after cardiac arrest or unstable ventricular tachycardia or ventricular fibrillation [n= 1963]) and primary prevention (involving patients at increased risk for sudden cardiac death but without documented cardiac arrest, ventricular fibrillation, or ventricular tachycardia [n= 2946]). Regardless of baseline risk, ICDs were equally efficacious in preventing sudden cardiac death in both types of trials (RR, 0.50 [CI, 0.38 to 0.66] for secondary prevention vs. 0.37 [CI, 0.27 to 0.50] for primary prevention). However, the magnitude of benefit in total mortality varied within the primary prevention trials depending on baseline risk for sudden cardiac death. Conclusions: Implantable cardioverter defibrillators prevent sudden cardiac death regardless of baseline risk. However, their impact on total mortality is sensitive to baseline risk for arrhythmic death. Decisions about resource allocation for ICDs depend on accurate stratification of patients according to risk.
Spliceosomal gene aberrations are rare, coexist with oncogenic mutations, and are unlikely to exert a driver effect in childhood MDS and JMML
Authors: Shinsuke Hirabayashi, Christian Flotho, Jessica Moetter, Michael Heuser, Henrik Hasle, Bernd Gruhn, Thomas Klingebiel, Felicitas Thol, Brigitte Schlegelberger, Irith Baumann, Brigitte Strahm, Jan Stary, Franco Locatelli, Marco Zecca, Eva Bergstraesser, Michael Dworzak, Marry M. van den Heuvel-Eibrink, Barbara De Moerloose, Seishi Ogawa, Charlotte M. Niemeyer, Marcin W. Wlodarski
Journal: Blood (2012)
Cystinosis: Progress in a Prototypic Disease
Authors: William A. Gahl, Jess G. Thoene, Jerry A. Schneider, Sean O'Regan, Muriel I. Kaiser-Kupfer, Toichiro Kuwabara
Journal: Annals of Internal Medicine (1988)

Objective: To review the history, basic defect, pathogenesis, clinical manifestations, diagnosis, and treatment of nephropathic cystinosis. Design: Lysosomal membrane transport studies, clinical reports, and a historically controlled 7-year trial of oral cysteamine therapy. Setting: University centers in the United States and Canada. Patients: One hundred forty-eight children, aged 0 to 12, with nephropathic cystinosis before renal transplant, who had renal tubular Fanconi syndrome, failure to grow, corneal cystine crystals, and elevated leukocyte cystine; 34 patients, aged 9 to 29, after transplant, some with visual impairment, corneal erosions, pancreatic dysfunction, or neurologic deterioration. Intervention: Before transplant, replacement of renal losses, and treatment with oral cysteamine (55 mg/kg body weight · d for 1 to 6 years) and topical cysteamine eyedrops (0.1%, 1 drop/h while awake, for 6 months). After transplant, oral cysteamine and symptomatic treatment of late complications. Measurements and Main Results: Untreated patients reached renal failure at age 10. Oral cysteamine lowered leukocyte cystine over 80%, and in patients before transplant, improved growth and preserved renal function (mean creatinine clearance [± SE], 0.64 ± 0.04 mL/s · 1.73 m2 [38.5 ± 2.5 mL/min · 1.73 m2] in the cysteamine group compared with 0.50 ± 0.03 mL/s · 1.73 m2 [29.7 ± 2.0 mL/min · 1.73 m2] in controls; 95% CI for the difference, 1.8 to 15.8). Cysteamine eyedrops cleared the corneal crystals of two children less than 2 years old. Conclusions: Cystinosis is a lysosomal storage disease due to impaired transport of cystine out of lysosomes. In young children, growth can be improved and renal deterioration delayed or prevented by oral cysteamine. Nonrenal complications after transplant might be prevented with long-term oral cysteamine.
Racial and Ethnic Disparities in Health Care
Authors: M. E. Nassar
Journal: Annals of Internal Medicine (2005)

Letters18 January 2005Racial and Ethnic Disparities in Health CareM. E. Nassar, MD, PhDM. E. Nassar, MD, PhDFrom Pittsford, NY 14534-2566.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-142-2-200501180-00017 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:The American College of Physicians' position paper on racial and ethnic disparities in health care (1) is of prime importance and is a step in the right direction. However, my concern is that the root causes of these disparities have not been adequately explored. During the past 30 years, the business aspect of medicine has invaded the sacrosanct physician–patient relationship. As a result, family physicians have disappeared, especially in rural areas, and have been replaced by health maintenance organizations and organized group physician practices, which gravitated toward cities and large university medical centers. Unless minority physicians could ...Reference1. Groman R, Ginsburg J; American College of Physicians. Racial and ethnic disparities in health care: a position paper of the American College of Physicians. Ann Intern Med. 2004;141:226-32. [PMID: 15289223] LinkGoogle Scholar Author, Article, and Disclosure InformationAffiliations: From Pittsford, NY 14534-2566. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoRacial and Ethnic Disparities in Health CareRacial and Ethnic Disparities in Health Care Kenneth L. Cohen Racial and Ethnic Disparities in Health Care Charles K. Francis Metrics 18 January 2005Volume 142, Issue 2Page: 153KeywordsAcademic medicineHealth careHealth disparitiesRural areasSub-specialty careSurgery ePublished: 18 January 2005 Issue Published: 18 January 2005 CopyrightCopyright © 2005 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
Plasmapheresis and Specific Component Therapy of Bleeding Disorders.
Authors: Edward R. Burka
Journal: Annals of Internal Medicine (1971)

Meeting Abstracts1 May 1971Plasmapheresis and Specific Component Therapy of Bleeding Disorders.Edward R. Burka, M.D., F.A.C.P.Edward R. Burka, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-74-5-826_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptPlasmapheresis has successfully provided specific component therapy for patients lacking circulating coagulation factors or platelets. The experience and methods of a hospital blood bank that processes more than 3,000 plasma donors per year is reviewed. Six-hundred and fifty units of cryoprecipitate and 350 units of platelets are provided by the program each month. Donors are bled two 500-ml increments of blood on each of 2 days per week. After each unit is taken the cells are separated by centrifugation in a three-bag closed system and returned to the donor. The platelet-rich plasma is further centrifuged to provide a platelet concentrate.... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Philadelphia, Pa. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1971Volume 74, Issue 5Page: 826-826KeywordsBlood banksBlood plasmaCellsCoagulation factorsHemorrhagePlatelets Issue Published: 1 May 1971 PDF DownloadLoading ...
The value of bacteriology and serology in the diagnosis of necrotizing fasciitis
Authors: BARBARA J.LEPPARD, D.V. SEAL
Journal: British Journal of Dermatology (1983)

Fourteen patients with necrotizing fasciitis are described. In thirteen the cause was Streptococcus pyogenes [Group A beta haemolytic streptococcus (BHS)]; in the fourteenth, Staphylococcus aureus was responsible. In the acute fulminating form of the disease, BHS can be cultured from the affected tissues. In the less acute form, particularly when the patient has been previously treated with antibiotics, other bacteria colonize the tissues and the BHS cannot be isolated. Serological evidence of infection with Streptococcus pyogenes can be ascertained in all such patients by finding high levels of anti-desoxyribonuclease B and anti-hyaluronidase. Measurement of the anti-streptolysin O titre is not helpful. Once the diagnosis is made, surgical removal of all necrotic tissue is still the treatment of choice.
Assaults on doctors.
Authors: A Fraser-Moodie, D I Rowley
Journal: BMJ (1978)

reports on bronchodilator infusions which were given as initial therapy for acute asthma and for short periods only, where it would be a simple matter to change treatment for those who failed to respond.We cannot really contest his views on the ethical committee, which may apply criteria more stringent than elsewhere.The information presented in our paper suggested that a salbutamol infusion of 10 g/min is no more effective than the amino- phylline infusion, and Professor Grant may well be correct to state, as we inferred, that with adequate administration of nebulised bronchodilator drugs an intravenous infusion may not make a significant contribution to airway function.The analysis for significant differences in lung function between the two infusion groups included all the patients up to the time of withdrawal from the study if before 36 h.Dr Anderson assumes incorrectly that the data on those patients withdrawn before 36 h were not included in these analyses.The fact that of the six patients withdrawn from the salbutamol group before 36 h, two were responding faster than the group as a whole makes the response between the two groups less marked than Dr Anderson suggests.
Noninvasive assessment of hepatic triglyceride content in humans with13C nuclear magnetic resonance spectroscopy
Authors: K F Petersen, A B West, A Reuben, D L Rothman, G I Shulman
Journal: Hepatology (1996)

Hepatic lipid content was assessed noninvasively in 15 patients with hepatic steatosis by 13C nuclear magnetic resonance (NMR) spectroscopy, and compared in a double-blind fashion with histological grading and morphometric quantitation of fat in liver biopsies taken within 2 weeks of the study. The lipid content in the liver biopsies was expressed as the volume fraction of total parenchyma occupied by fat. Hepatic triglyceride content was determined by comparing the 13C NMR signal intensity in vivo with the signal intensity obtained from a lipid phantom of known concentrations. There was an approximately 30-fold increase in the 13C NMR signals of the saturated carbons (methyl/methylene [CH2]n) region of hepatic triglycerides from patients with grade 4 steatosis compared with those with grade 0, yielding a good dynamic range for measuring hepatic triglyceride content. The correlation coefficient between the morphometric and 13C NMR techniques was 0.89 (P < .01). These studies demonstrate that 13C NMR spectroscopy can be used to noninvasively assess hepatic triglyceride content in humans. This method may be clinically useful for diagnosis and follow-up of patients with hepatic steatosis.
Caveolae-Mediated internalization of extracellular HIV-1 tat fusion proteins visualized in real time
Authors: Aldo Ferrari, Vittorio Pellegrini, Caterina Arcangeli, Antonio Fittipaldi, Mauro Giacca, Fabio Beltram
Journal: Molecular Therapy (2003)

The Tat protein from HIV-1, when fused with heterologous proteins or peptides, can traverse cell membranes. This ability has generated great interest due to potential therapeutic applications. However, the relevant cellular pathway and its dynamics have not been elucidated yet. Here we unravel the intracellular fate of exogenously added Tat fused with green fluorescent protein (GFP) in live HeLa and CHO cells, from the early interaction with the plasma membrane up to the long-term accumulation in the perinuclear region. We demonstrate that the internalization process of full-length Tat and of heterologous proteins fused to the transduction domain of Tat exploits a caveolar-mediated pathway and is inhibited at 4 degrees C. Remarkably, a slow linear movement toward the nucleus of individual GFP-tagged Tat-filled caveolae with an average velocity of 3 micro m/h was observed. No fluorescence was observed in the nucleus, possibly suggesting that Tat fusion protein unfolding is required for nuclear translocation. In addition, early sensitivity to cytochalasin-D treatment indicates the essential role of the actin cytoskeleton in the displacement of Tat vesicles toward the nucleus. Our results imply that HIV-1 Tat mediates the internalization of protein cargos in a slow and temperature-dependent manner by exploiting the caveolar pathway.
Limitations of Continuous Ambulatory Electrocardiogram Monitoring for Detecting Coronary Artery Disease
Authors: MICHAEL H. CRAWFORD
Journal: Annals of Internal Medicine (1978)

To assess the value of continuous ambulatory electrocardiogram (ECG) monitoring for detecting coronary artery disease in symptomatic patients, we evaluated 70 patients with chest pain and normal resting ECGs prospectively by calibrated ambulatory monitoring, graded treadmill exercise, and selective coronary cineangiography. Ischemic-type ST-wave changes were detected by monitoring in 24 of the 39 patients with coronary artery disease (62% sensitivity). Twenty-six of the 39 patients had a positive treadmill (67% sensitivity). Of the 31 patients without coronary disease on angiography, 19 had negative monitoring studies (61% specificity). The treadmill was negative in 23 of these 31 patients (75% specificity). When the results of both tests were combined, 85% of the cases of coronary artery disease were detected, but only 52% of the patients without disease had negative studies. We conclude that continuous ambulatory monitoring is of limited value for detecting or excluding coronary artery disease in symptomatic patients with normal resting ECGs.
MATERNAL IMPRESSION "MARKS" CHILD FOR A FROG.
Authors: J. W. COOLIDGE
Journal: JAMA (1902)

Mrs. R., aged 31, of good intellectual ability, and not superstitious, gave birth, March 13, 1902, to a stillborn, seven months' male child. Fetal movements were noticeable the previous evening and death seemed to have been due to a long second stage, it being 3½ hours in length. The child having no neck, the head was almost immovable on the shoulders, so much so that it was a left brow presentation, the left shoulder following immediately, and so rigid were these parts that the maternal coccyx was strained backward sufficiently to cause extreme pain for a few days. The child's eyes protrude far beyond the brows, and there appears to be no brain cavity, except two little sacs on the back of the head, with a smaller one between and posterior (cerebellum). There are two parallel lines of bony prominences extending from the back of the head downward as far
More collaboration is needed about benefits of new genetic screening tests
Authors: B. O'Connor
Journal: BMJ (1998)

EDITOR—Gill and Richards request a full and rigorous assessment of the benefits and costs of introducing new genetic screening tests.1 They point out the need for collaboration between geneticists, public health specialists, and primary care teams and emphasise the importance of the general public.

A spot analysis of data available for East Sussex, Brighton and Hove Health Authority for the current financial year (1997-8) from an eligible general population …
Role of Ca<sup>2+</sup>/calmodulin-dependent protein kinase (CaMK) in excitation–contraction coupling in the heart
Authors: Lars S. Maier, Donald M. Bers
Journal: Cardiovascular Research (2006)

Calcium (Ca(2+)) is the central second messenger in the translation of electrical signals into mechanical activity of the heart. This highly coordinated process, termed excitation-contraction coupling or ECC, is based on Ca(2+)-induced Ca(2+) release from the sarcoplasmic reticulum (SR). In recent years it has become increasingly clear that several Ca(2+)-dependent proteins contribute to the fine tuning of ECC. One of these is the Ca(2+)/calmodulin-dependent protein kinase (CaMK) of which CaMKII is the predominant cardiac isoform. During ECC CaMKII phosphorylates several Ca(2+) handling proteins with multiple functional consequences. CaMKII may also be co-localized to distinct target proteins. CaMKII expression as well as activity are reported to be increased in heart failure and CaMKII overexpression can exert distinct and novel effects on ECC in the heart and in isolated myocytes of animals. In the present review we summarize important aspects of the role of CaMKII in ECC with an emphasis on recent novel findings.
Selective retroinfusion of GSH and cariporide attenuates myocardial ischemia–reperfusion injury in a preclinical pig model
Authors: C Kupatt
Journal: Cardiovascular Research (2004)

Objective: Reperfusion after ischemia may contribute to loss of myocardial function and increase in infarct size. Scavenging of reactive oxygen species (ROS) by glutathione (GSH) and inhibition of the sodium-proton-exchanger by cariporide are both capable of reducing myocardial reperfusion injury. We tested the efficacy of both agents applied regionally into the myocardium immediately before reperfusion. Methods: Neonatal rat cardiomyocytes (NRCMs) were exposed to either hypoxia (H, 8 h)/reoxygenation (R, 1 h) or H2O2 (300 μM) in the presence or absence of GSH (10 mg/ml). In pigs (n=5 per group), percutaneous LAD occlusion was performed for 60 min. Application of GSH (250 mg/kg) and/or cariporide (1 mg/kg) was achieved by pressure-regulated retroinfusion of the anterior cardiac vein draining the ischemic area starting 5 min before reopening of the occluded LAD. Seven days later, subendocardial segment shortening (SES) was analyzed by sonomicrometry. Infarct size was determined by methylene-blue staining of the non-ischemic area and tetrazolium red staining of the viable myocardium in the area at risk (AAR). Results: NRCM incubated with GSH (10 mg/ml) survived H/R or H2O2 (0.3 mM) to a larger extent than untreated cells. In pigs, infarct size of untreated hearts (51±6% of the AAR) was not significantly altered by GSH or cariporide retroinfusion alone (41±3% and 42±6%). In contrast, combined retroinfusion of cariporide and GSH significantly reduced infarct size (29±3%). SES of the infarcted area was improved only after cariporide/GSH retroinfusion as compared to untreated hearts. Additional systemic application of CD18-antibody IB4 (1.5 mg/kg) did not alter infarct size or SES in comparison to GSH/cariporide retroinfusion alone. Conclusion: Timely application of GSH scavenging ROS and cariporide targeting ion imbalance provides cardioprotection to the postischemic heart, which is superior to either treatment alone. The lack of an effect of additional IB4 treatment may indicate that GSH/cariporide retroinfusion itself affects leukocyte-dependent reperfusion injury.