tbuckley/cabot-search huggingface dataset:
Carvedilol blocks β2- more than β1-adrenoceptors in human heart
Authors: P MOLENAAR, T CHRIST, U RAVENS, A KAUMANN
Journal: Cardiovascular Research (2005)

Objective: To understand the basis of the effectiveness of carvedilol in heart failure by determining its specific properties at human heart β1- and β2-adrenoceptors. Methods: The positive inotropic effects of noradrenaline (in the presence of the β2-selective antagonist ICI118551) and adrenaline (in the presence of the β1-selective antagonist CGP20712), mediated through β1- and β2-adrenoceptors, respectively, were investigated in atrial and ventricular trabeculae. The patch-clamp technique was used to investigate effects of noradrenaline and adrenaline on L-type Ca2+ current in human atrial myocytes. Results: Carvedilol was a 13-fold more potent competitive antagonist of the effects of adrenaline at β2-adrenoceptors (−logKB=10.13 ± 0.08) than of noradrenaline at β1-adrenoceptors (−logKB=9.02 ± 0.07) in human right atrium. Chronic carvedilol treatment of patients with non-terminal heart failure reduced the inotropic sensitivity of atrial trabeculae to noradrenaline and adrenaline 5.6-fold and 91.2-fold, respectively, compared to β1-blocker-treated patients, consistent with persistent preferential blockade of β2-adrenoceptors. In terminal heart failure carvedilol treatment reduced 1.8-fold and 25.1-fold the sensitivity of right ventricular trabeculae to noradrenaline and adrenaline, respectively, but metoprolol treatment did not reduce the sensitivity to the catecholamines. Increases of current (ICa,L) produced by noradrenaline and adrenaline were not different in atrial myocytes obtained from non-terminal heart failure patients treated with metoprolol or carvedilol, consistent with dissociation of both β-blockers from the receptors. Conclusions: Carvedilol blocks human cardiac β2-adrenoceptors more than β1-adrenoceptors, thereby conceivably contributing to the beneficial effects in heart failure. The persistent blockade of β-adrenoceptors is attributed to accumulation of carvedilol in cardiac tissue.
More US graduates opt for primary care
Authors: J Roberts
Journal: BMJ (1994)

More medical school graduates in the US this spring looked into their future and chose primary care. After almost a decade of losing graduate students to medical and surgical specialties, primary care specialties have made a strong comeback this year.

On 15 March, after months of interviewing, applying, and waiting, senior medical students in the US were handed confirmation of their choices of where they would spend their next few years of postgraduate training. For most, that was the day they committed themselves to a speciality. And, for the first time since 1988, …
Ergot Poisoning at Pont St. Esprit
Authors: None Gabbai, None Lisbonne, None Pourquier
Journal: BMJ (1951)

DISEASEBMEIsH dose to 100,000 units six-hourly was quite dramatic and a rapid improvement set in.Case 2 received 250,000 units three-hourly.After the first dose there was a sharp rise of temperature from 100 to 1040 F. (37.8 to 400 C.), the patient became violent and abusive, and he had to be given a sedative.Thereafter he improved rapidly and the temperature was normal by next morning.Suchett- Kaye drew attention to a reaction resembling the Jarisch-Herxheimer reaction which may occur at the beginning of treatment of Weil's disease with penicillin.Case 1 showed a slight rise of temperature, which might or might not have been of significance.In Case 2 the reaction was marked.Prognostically it may be regarded as a favourable sign, as it may mean that the strain of organism is sensitive to penicillin and is being destroyed.Case 4 showed no such reaction, and he went steadily downhill.He was jaundiced on admission, but his general condition was good.He received 100,000 units of penicillin initially and 50,000 units three-hourly thereafter.Necropsy revealed two striking features.The first was that neither macroscopically nor microscopically did the brain, lungs, liver, or kidneys appear to be irreparably damaged.The second was that a smear from the liver showed so many leptospires.One was left with the impression that had it been possible to destroy the organisms a few days earlier the outcome might not have been fatal.Case 3 had recovered spontaneously, but a course of 250,000 units of penicillin three-hourly was given for four days with the object of avoiding the carrier state or the possibility of smouldering renal damage.Patterson found that in his cases a large number of leptospires continued to be excreted in the urine for many weeks after clinical recovery. Summary and ConclusionsFour cases of Weil's disease treated with penicillin are described, including one which was presuimably contracted by actual rat-bite.
Aetiology of community-acquired pneumonia: a prospective study among adults requiring admission to hospital.
Authors: R Bohte, R van Furth, P J van den Broek
Journal: Thorax (1995)

BACKGROUND--The prevalence of microorganisms causing community-acquired pneumonia in patients who required admission to hospital was investigated and the percentage of cases whose aetiology remained unknown due to the study design and logistical problems estimated. METHODS--Between January 1991 and April 1993 all patients with community-acquired pneumonia admitted to six hospitals were included in the study. Aetiological diagnosis, categorised as definite, probable and possible, was based on the results of routine microbiological and serological tests. RESULTS--Three hundred and thirty four patients with a median age of 65 (range 17-92) years were enrolled in the study. The diagnosis of community-acquired pneumonia was definite in 108 cases, and probable or possible in 73 and 27 cases, respectively, including dual infections. Streptococcus pneumoniae was the predominant pathogen (27%) followed by viruses and Haemophilus influenzae (both about 8%) and Mycoplasma pneumoniae (6%). Chlamydia spp (3%) and Legionella pneumophila (2%) were less frequently detected. No diagnosis was made in 45% of the cases. With adjustment for anti-microbial therapy before admission and for other logistical considerations, it is estimated that the aetiology could have been ascertained in 65% of the cases. CONCLUSIONS--Streptococcus pneumoniae is the most frequently detected cause of community-acquired pneumonia. The inability to detect a micro-organism results mainly from the use of routine diagnostic tests and, to a lesser extent, from logistical problems or the use of antibiotics before admission.
Smoke inhalation in firemen.
Authors: K M Unger, R M Snow, J M Mestas, W C Miller
Journal: Thorax (1980)

Thirty firemen were studied with pulmonary function tests immediately after a severe smoke exposure and then one and a half and 18 months later in order to evaluate acute and chronic changes in their spirometry. The results were compared with predicted values and with those from a group of closely matched control subjects. We found no significant differences between the acute post-exposure spirometry values and those recorded at six weeks and 18 months later. A trend toward an increased rate of volume loss in the FVC and FEV1 was noted which is similar to other published observations. However, we did find a significant decrement in FVC compared with predicted value, and in FVC and FEV1 compared with control subjects. This is further evidence that firemen may develop lung disease related to their occupational exposure.
Hippocampal and Amygdalar Volumes in Dissociative Identity Disorder
Authors: Eric Vermetten
Journal: American Journal of Psychiatry (2006)

Objective: Smaller hippocampal volume has been reported in several stress-related psychiatric disorders, including posttraumatic stress disorder (PTSD), borderline personality disorder with early abuse, and depression with early abuse. Patients with borderline personality disorder and early abuse have also been found to have smaller amygdalar volume. The authors examined hippocampal and amygdalar volumes in patients with dissociative identity disorder, a disorder that has been associated with a history of severe childhood trauma. Method: The authors used magnetic resonance imaging to measure the volumes of the hippocampus and amygdala in 15 female patients with dissociative identity disorder and 23 female subjects without dissociative identity disorder or any other psychiatric disorder. The volumetric measurements for the two groups were compared. Results: Hippocampal volume was 19.2% smaller and amygdalar volume was 31.6% smaller in the patients with dissociative identity disorder, compared to the healthy subjects. The ratio of hippocampal volume to amygdalar volume was significantly different between groups. Conclusions: The findings are consistent with the presence of smaller hippocampal and amygdalar volumes in patients with dissociative identity disorder, compared with healthy subjects.
Improved Prediction of Fatal Myocardial Infarction Using the Ankle Brachial Index in Addition to Conventional Risk Factors
Authors: A.J. Lee, J.F. Price, M.J. Russell, F.B. Smith, M.C.W. van Wijk, F.G.R. Fowkes
Journal: Circulation (2004)

Background— Prediction of major cardiovascular and cerebrovascular events using conventional risk factor models is limited. Noninvasive measures of subclinical atherosclerosis such as the ankle brachial index (ABI) could improve risk prediction and provide more focused primary prevention strategies. We wished to determine the added value of a low ABI in the prediction of long-term risk of cardiovascular and cerebrovascular events and death. Methods and Results— In 1988, 1592 men and women 55 to 74 years of age were randomly selected from the age-sex registers of 11 general practices in Edinburgh, Scotland, and followed up over a period of 12 years for incident events. After adjustment for age and sex, an ABI ≤0.9 was predictive of an increased risk of fatal myocardial infarction (MI), cardiovascular death, all-cause death, combined fatal and nonfatal MI, and total cardiovascular events. After further adjustment for prevalent cardiovascular disease, diabetes, and conventional risk factors, a low ABI was independently predictive of the risk of fatal MI. Addition of the ABI significantly ( P ≤0.01) increased the predictive value of the model for fatal MI compared with a model containing risk factors alone. Comparison of areas under receiver operator characteristic curves confirmed that a model including the ABI discriminated marginally better than one without. Conclusions— Addition of the ABI significantly improved prediction of fatal MI over and above that of conventional risk factors. We recommend that the ABI be incorporated into routine cardiovascular screening and that the potential of its inclusion into cardiovascular scoring systems (with a view to improving their accuracy) now be examined.
TCT-405 SYMPLICITY HTN-3: Outcomes in the African-American and non-African American Populations
Authors: John Flack, George L. Bakris, David Kandzari, Barry T. Katzen, Martin Leon, Laura Mauri, William W. O'Neill, Suzanne Oparil, Krishna Rocha-Singh, Raymond R. Townsend, Deepak L. Bhatt
Journal: Journal of the American College of Cardiology (2014)
Genetically Engineered Human Islets Protected From CD8-mediated Autoimmune Destruction In Vivo
Authors: Arnaud Zaldumbide, Gonnie Alkemade, Françoise Carlotti, Tatjana Nikolic, Joana RF Abreu, Marten A Engelse, Anja Skowera, Eelco J de Koning, Mark Peakman, Bart O Roep, Rob C Hoeben, Emmanuel JHJ Wiertz
Journal: Molecular Therapy (2013)

Islet transplantation is a promising therapy for type 1 diabetes, but graft function and survival are compromised by recurrent islet autoimmunity. Immunoprotection of islets will be required to improve clinical outcome. We engineered human β cells to express herpesvirus-encoded immune-evasion proteins, "immunevasins." The capacity of immunevasins to protect β cells from autoreactive T-cell killing was evaluated in vitro and in vivo in humanized mice. Lentiviral vectors were used for efficient genetic modification of primary human β cells without impairing their function. Using a novel β-cell–specific reporter gene assay, we show that autoreactive cytotoxic CD8+ T-cell clones isolated from patients with recent onset diabetes selectively destroyed human β cells, and that coexpression of the human cytomegalovirus-encoded US2 protein and serine proteinase inhibitor 9 offers highly efficient protection in vitro. Moreover, coimplantation of these genetically modified pseudoislets with β-cell–specific cytotoxic T cells into immunodeficient mice achieves preserved human insulin production and C-peptide secretion. Collectively, our data provide proof of concept that human β cells can be efficiently genetically modified to provide protection from killing mediated by autoreactive T cells and retain their function in vitro and in vivo. Islet transplantation is a promising therapy for type 1 diabetes, but graft function and survival are compromised by recurrent islet autoimmunity. Immunoprotection of islets will be required to improve clinical outcome. We engineered human β cells to express herpesvirus-encoded immune-evasion proteins, "immunevasins." The capacity of immunevasins to protect β cells from autoreactive T-cell killing was evaluated in vitro and in vivo in humanized mice. Lentiviral vectors were used for efficient genetic modification of primary human β cells without impairing their function. Using a novel β-cell–specific reporter gene assay, we show that autoreactive cytotoxic CD8+ T-cell clones isolated from patients with recent onset diabetes selectively destroyed human β cells, and that coexpression of the human cytomegalovirus-encoded US2 protein and serine proteinase inhibitor 9 offers highly efficient protection in vitro. Moreover, coimplantation of these genetically modified pseudoislets with β-cell–specific cytotoxic T cells into immunodeficient mice achieves preserved human insulin production and C-peptide secretion. Collectively, our data provide proof of concept that human β cells can be efficiently genetically modified to provide protection from killing mediated by autoreactive T cells and retain their function in vitro and in vivo.
ANEURYSM OF THE VENTRICLE OF THE HEART
Authors: MARSHALL N. FULTON
Journal: JAMA (1941)

The prevalence of coronary occlusion and myocardial infarction as a disease entity has led to widespread interest in this condition, its complications and the sequelae. Among the less common end results of infarct of the heart is the formation of ventricular aneurysm. Aneurysm of the ventricle may occur from causes other than infarction, namely from abscess of the heart wall, from trauma, from ulcerative lesions of bacterial endocarditis or from congenital defects. Instances of this type, however, are rare. The majority of ventricular aneurysms arise as a result of infarction following coronary thrombosis. Clinical interest in this problem has received stimulus from the fact that ventricular aneurysm can be diagnosed with accuracy before death and is known to be compatible in some instances with several years of reasonably active life. My purpose in this communication is to review the pathologic, clinical and roentgenologic features of ventricular aneurysm, to report the
Diet and Risk of Amyotrophic Lateral Sclerosis
Authors: Michael Swash
Journal: JAMA Neurology (2014)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Neurology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Neurology journal
Cystic Fibrosis in Adults
Authors: Jonathan B. Zuckerman
Journal: Annals of Internal Medicine (1999)

Medical Writings: Book Notes18 May 1999Cystic Fibrosis in AdultsJonathan B. Zuckerman, MD and Robert M. Kotloff, MDJonathan B. Zuckerman, MDUniversity of Pennsylvania Medical Center, Philadelphia, Pennsylvania. (Zuckerman, Kotloff)Search for more papers by this author and Robert M. Kotloff, MDUniversity of Pennsylvania Medical Center, Philadelphia, Pennsylvania. (Zuckerman, Kotloff)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-130-10-199905180-00026 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Yankaskas JR, Knowles MR; eds. 528 pages. Philadelphia: Lippincott-Raven; 1999. $99.95. ISBN 0781710111. Order phone 800-777-2295.Field of medicine: Pulmonary medicine, gastroenterology, and genetics.Format: Hardcover book.Audience: Adult pulmonologists, other medical subspecialists, respiratory and physical therapists, nutritionists, and nurse specialists.Purpose: To provide comprehensive coverage of the genetics, pathophysiology, clinical features, and treatment of cystic fibrosis, with particular emphasis on topics relevant to the care of adult patients.Content: The book contains 23 chapters organized into four sections. The first section covers the pathogenesis of cystic fibrosis at the cellular level, explaining derangements in epithelial ion transport, mucus composition, ... Author, Article, and Disclosure InformationAffiliations: University of Pennsylvania Medical Center, Philadelphia, Pennsylvania. (Zuckerman, Kotloff) PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 18 May 1999Volume 130, Issue 10Page: 866KeywordsClinical geneticsCystic fibrosisNursesNutritionPathogenesisPatientsPulmonary diseasesPulmonary medicineReproductive systemSub-specialty care ePublished: 15 August 2000 Issue Published: 18 May 1999 Copyright & PermissionsCopyright © 1999 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Experience with a Computer-Based Drug Test Interaction Surveillance System.
Authors: D. S. Young
Journal: Annals of Internal Medicine (1973)

Meeting Abstracts1 May 1973Experience with a Computer-Based Drug Test Interaction Surveillance System.D. S. Young, M.D., R. B. Friedman, M.D., L. Pastener, B.S.D. S. Young, M.D.Search for more papers by this author, R. B. Friedman, M.D.Search for more papers by this author, L. Pastener, B.S.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-78-5-814_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptClinical reports of drug effects on laboratory test results have been appearing with increasing frequency. Although it is apparent that such interactions can seriously affect the clinical value of laboratory procedures, it is also clear that the number of such interactions has long exceeded what a physician might reasonably be expected to remember. To assist physicians in this task, we compiled a computerized file of over 13 000 clinically documented drug-test interactions. A computer program was then written that accepted as input the data on drugs administered to patients and patients' laboratory test results. If a test result fell outside... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Bethesda, Maryland PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1973Volume 78, Issue 5Page: 814-814KeywordsClinical laboratoriesComputersDrug interactionsDrugsLaboratory testsPatientsResearch laboratoriesSoftware tools Issue Published: 1 May 1973 PDF DownloadLoading ...
Maleness as Risk Factor for Slowly Progressive IDDM
Authors: Tetsuro Kobayashi, Koji Nakanishi, Tadao Sugimoto, Tokuji Itoh, Toshio Murase, Kinori Kosaka, Kimiyoshi Tsuji
Journal: Diabetes Care (1989)

The effect of sex on longitudinal changes in serum C-peptide immunoreactivity (CPR) response to the oral glucose tolerance test (OGTT) was examined up to 48 mo in 30 islet cell antibody-positive (ICA+), non-insulindependent diabetes mellitus (NIDDM) subjects (15 men, 15 women) who were matched for age, duration of diabetes, and mode of treatment. The subjects were recruited from 2858 NIDDM patients screened for ICA between 1980 and 1984. In male NIDDM subjects, CPR levels to OGTT decreased insidiously, and 8 of 15 men developed the insulin-dependent state with abolished CPR. Only 2 female NIDDM subjects progressed to the insulin-dependent state (P &amp;lt; .05, women vs. men). Thus, CPR in female subjects tended to decrease less than in male subjects. There were no significant differences between the two groups in human leukocyte antigens (HLA) or titer of ICA during the follow-up period. These results suggest that maleness is a major risk factor for slowly progressive β-cell dysfunction in adult-onset insulin-dependent diabetes mellitus (IDDM).
P93 Clinical Outcomes and Patient Satisfaction Following Initiation of the TOBI Podhaler in CF Adults
Authors: CJ Brown, EF Nash, V Carrolan, R Rashid, JL Whitehouse
Journal: Thorax (2012)

<h3>Background</h3> In the clinical trial setting, TOBI Podhaler (TIP) has been shown to be non-inferior to nebulised Tobramycin Inhalation Solution (TIS) in CF subjects in terms of effects on lung function, with increased adverse events but overall superior patient satisfaction. However, there is currently little ‘real world’ evidence of tolerance and effectiveness of TIP. <h3>Aim</h3> To assess the experience of CF adults receiving TIP at our large regional UK adult CF centre. <h3>Methods</h3> We report the preliminary results of a prospective observational study to evaluate changes in lung function, tolerability and antibiotic requirements of 73 CF adults that have received at least one dose of TIP at our centre to date. Patients also completed a visual analogue scale (VAS) score of tolerance, convenience, satisfaction and likelihood to continue (1 = very satisfied/not at all severe/very likely, 10 = not at all satisfied/very severe/not at all likely) at their 28-day review. <h3>Results</h3> Adverse events (AEs) were common following the test dose (most commonly cough in 24/73, 32.9%), although only 1 patient discontinued treatment, due to a 10% drop in FEV1% predicted. 27/72 patients so far have completed 28 days treatment, with median change in FEV1% predicted of –1.7% (IQR –6.1 to 2.4%). 12/27 patients (44.4%) reported AEs at their 28-day review; most commonly cough (10 patients, 37.0%), with median VAS score for severity of all AEs of 4/10. 12/27 patients (44.4%) were commenced on oral or IV antibiotics for pulmonary exacerbation at their 28-day review. Median VAS scores for overall satisfaction, ease of administration, and likelihood to continue were all 1/10. 12/72 patients to date have discontinued TIP before completion (10 patients) or at completion (2 patients) of 28 days treatment, 8 (66.7%) of whom were previously intolerant of TIS. The most common reason for discontinuation was cough (9/12 patients, 75.0%), with median VAS score for severity of all AEs 7/10. <h3>Conclusion</h3> Despite experiencing a high incidence of adverse events, patients commencing TIP report high levels of treatment satisfaction.