tbuckley/cabot-search huggingface dataset:
Impaired activation of murine platelets lacking Gαi2
Authors: Hans-Michael Jantzen, David S. Milstone, Laurent Gousset, Pamela B. Conley, Richard M. Mortensen
Journal: Journal of Clinical Investigation (2001)

The intracellular signaling pathways by which G protein–coupled receptors on the platelet surface initiate aggregation, a critical process for hemostasis and thrombosis, are not well understood. In particular, the contribution of the Gi pathway has not been directly addressed. We have investigated the activation of platelets from mice in which the gene for the predominant platelet Gαi subtype, Gαi2, has been disrupted. In intact platelets from Gαi2-deficient mice, the inhibition of adenylyl cyclase by ADP was found to be partially impaired compared with wild-type platelets. Moreover, both ADP-dependent platelet aggregation and the activation of the integrin αIIbβ3 (GPIIb-IIIa) were strongly reduced in platelets from Gαi2-deficient mice. In addition, Gαi2-deficient platelets displayed impaired activation at low thrombin concentrations. This defect was mimicked by blocking the adenylyl cyclase–coupled platelet ADP receptor (P2Y12) on wild-type platelets with a selective antagonist. These observations suggest that Gαi2 is involved in the inhibition of platelet adenylyl cyclase in vivo and is a critical component of the signaling pathway for integrin activation by ADP, resulting in platelet aggregation. In addition, thrombin-dependent activation of mouse platelets is mediated, at least in part, by secreted ADP acting on the Gαi2–linked ADP receptor.
Advances in Transplantation
Authors: Edgar H. Pierce
Journal: JAMA (1994)

<b>Alloimmunity: 1993 and Beyond</b>, edited by Sandra Taddie Nance, 213 pp, members $25, nonmembers $35, ISBN 1-56395-025-1, order No. 935620, Bethesda, Md, American Association of Blood Banks, 1993. These three publications, a few of the many by the American Association of Blood Banks (AABB), based on annual seminars and published each year for the educational support of its membership and the general blood bank community, represent the useful aspects of collective knowledge gathered in an organized and consistent way. The editors and authors attempt to summarize the current thinking in their fields; although some topics may seem narrow, taken as a whole they are very applicable to clinical science and a useful reference to others. Organ transplantation has garnered much attention in the nation, from families and transplant teams to
High prevalence of the His63Asp HFE mutation in italian patients with porphyria cutanea tarda
Authors: Maurizio Sampietro, Alberto Piperno, Loredana Lupica, Cristina Arosio, Anna Vergani, Noemi Corbetta, Ida Malosio, Michela Mattioli, Anna Ludovica Fracanzani, Maria Domenica Cappellini, Gemino Fiorelli, Silvia Fargion
Journal: Hepatology (1998)

Sporadic porphyria cutanea tarda (PCT) is caused by a reduced activity of uroporphyrinogen decarboxylase (URO-D) in the liver. Mild to moderate iron overload is common in PCT, as iron is one of the factors which trigger the clinical manifestations of the disease through the inactivation of URO-D. A role for genetic hemochromatosis in the development of iron overload in sporadic PCT has been hypothesized in the past. The aim of this work was to investigate whether mutations of HFE, which is a candidate gene for hemochromatosis, play the role of genetic susceptibility factors for PCT in Italian patients, who have a high prevalence of acquired triggering factors, such as hepatitis C virus (HCV) chronic infection and alcohol. We determined HFE genotypes of 68 male patients with PCT. Our data do not confirm an association of PCT with the Cys282Tyr HFE mutation, strongly associated with hemochromatosis in Northern European countries. A second mutation of HFE, His63Asp, however, had a significantly increased frequency as it was present in half of the patients. Surprisingly, the presence of the His63Asp mutation was not related to the iron status of patients, suggesting that a subtle abnormality of iron metabolism induced by this mutation could escape detection by the standard parameters of iron status. In PCT patients with liver disease, the presence of the mutation could contribute to the inactivation of URO-D, either directly or through a synergistic action with other factors that cause liver damage.
Non-fatal portal pyaemia complicating Crohn's disease of the terminal ileum.
Authors: H al-Jahdali, C Pon, W G Thompson, F R Matzinger
Journal: Gut (1994)

A 40 year old woman with known Crohn9s disease of the ileum but no abscess was found to have hepatic portal venous gas by computed tomography. Aggressive antibiotic treatment led to recovery and the ileum was resected two weeks later.
IgG and IgG4 Isotype Antibodies to Fel d 1 In Allergic and Non-allergic Students (n=963): Relationship to Symptoms of Asthma
Authors: T.A.E. Platts-Mills, B. Lundback, J.M. Roper, M. Mori, E. Ronmark
Journal: Journal of Allergy and Clinical Immunology (2011)
Sewage sludge as a source of cadmium in soil–plant–animal systems
Authors: D. E. Baker, M. C. Amacher, R. M. Leach
Journal: Environmental Health Perspectives (1979)

The objective of this presentation is to relate the abundance and mobility of Cd in components of terrestrial ecosystems with implications for land utilization of sewage sludge. The uptake of Cd by crop plants is a function of the quantity of the element in the soil plus other soil factors affecting the Cd ion activity or electrochemical potential at the plant root surface. The natural abundance of Cd in soils has been reported as 0.5 μg/g which is higher than the background level of 0.2 μg/g found in soils studied in Pennsylvania. Experimental results indicate that the plant availability of Cd increases with each soil addition. While the plant availability of Cd is decreased by liming to increase soil pH, it has not been possible to add Cd salts or sewage sludge Cd without significantly increasing plant uptake.Field studies have shown that land application of sewage sludge can be expected to increase the Cd concentration of corn leaves from a range of 0.05–0.1 μg/g to 1–3 μg/g. Two years after the last application of sludge which added up to 10 ppm Cd to the surface soil, corn grain, sorghum grain, wheat grain, and potatoes showed a 10- to 15-fold increase in Cd over background levels. Studies were conducted with chicks, laying hens, and meadow voles (Microtus Pennsylvanias) to assess the impact of this increase in plant Cd upon the food chain.Corn and sorghum plants were grown on soils with either inorganic or sludge fertilizer for the purpose of producing herbage for use in feeding trials with meadow voles. Eight diets and a synthetic control diet were formulated to study the effect of source (plant vs. inorganic) of Cd on tissue accumulation. Significant accumulation of Cd occurred in kidney and liver, but not muscle, of voles fed diets containing sludge fertilized corn (1.09 μg/g) or sludge fertilized sorghum (2.76 μg/g). The source of Cd had little influence on tissue accumulation.In studies with broiler chicks and laying hens, natural diets containing 0.2 ppm Cd were supplemented with 3 ppm of this element. As with the meadow voles, Cd readily accumulated in liver and kidney. Although the results were not statistically significant, 3 ppm dietary Cd doubled muscle Cd content. There was no transfer of Cd to egg in a long term (12 month) experiment with laying hens.Soil management programs have been developed to maintain animal dietary levels of Cd at less than 1.0 μg/g from the use of sewage sludge on land in Pennsylvania. However, it is concluded that this level over time may cause a significant accumulation of Cd in animal tissues. Interpretation of these results in relation to those for human intake of Cd and the long range health effects of Cd is required for the proper monitoring of sewage sludge applications on land used for production of crops which enter the food chain.
GM-CSF–dependent pSTAT5 sensitivity is a feature with therapeutic potential in chronic myelomonocytic leukemia
Authors: Eric Padron, Jeffrey S. Painter, Sateesh Kunigal, Adam W. Mailloux, Kathy McGraw, Jessica M. McDaniel, Eunhee Kim, Christopher Bebbington, Mark Baer, Geoffrey Yarranton, Jeffrey Lancet, Rami S. Komrokji, Omar Abdel-Wahab, Alan F. List, Pearlie K. Epling-Burnette
Journal: Blood (2013)
Emotions aroused by being on call
Authors: A S Naidoo
Journal: BMJ (1995)

<b>Background: </b> Fatigue is a common complaint in Parkinson disease (PD). We investigated fatigue in a cohort of previously untreated patients with early PD enrolled in the Earlier vs Later Levodopa (ELLDOPA) clinical trial. <b>Methods: </b> A total of 361 patients were enrolled in the randomized, double-blind, placebo-controlled ELLDOPA trial and assigned to receive placebo or carbidopa-levodopa 37.5/150 mg, 75/300 mg, or 150/600 mg daily for 40 weeks, followed by a 2-week medication washout period. Subjects who scored &gt;4 on the Fatigue Severity Scale were classified as fatigued. PD severity was assessed using the Unified Parkinson9s Disease Rating Scale (UPDRS), Hoehn-Yahr scale, and Schwab-England Activities of Daily Living Scale. A subgroup of subjects underwent [<sup>123</sup>I]-β-CIT SPECT to measure striatal dopamine transporter density. <b>Results: </b> Of the 349 ELLDOPA subjects who completed fatigue measures, 128 were classified as fatigued at baseline. The fatigued group was significantly more impaired neurologically (UPDRS, all subscales and Hoehn and Yahr staging) and functionally (Schwab-England Scale) but no significant differences were observed in β-CIT measurements between the two groups. Analysis of covariance showed a greater increase in fatigue score from baseline to the end of the 2-week washout in the placebo group (0.75 points) than in the three groups receiving levodopa (increases of 0.30 [150 mg/day], 0.36 [300 mg/day], and 0.33 [600 mg/day]; <i>p</i> = 0.03 for heterogeneity). <b>Conclusions: </b> Fatigue is a frequent symptom in early, untreated, non-depressed patients with Parkinson disease (PD), affecting over 1/3 of the patients in this cohort at baseline and 50% by week 42. Fatigue was associated with the severity of PD, and progressed less in patients treated with levodopa.
Changes of metabolic and inflammatory markers in HIV infection: glucose, lipids, serum Hs-CRP and myeloperoxidase
Authors: Danielle Cristyane Kalva Borato, Gisele Chibinski Parabocz, Sônia Regina Weber Ribas, Carlos Augusto Kalva-Filho, Luciana Maria Borba, Carmen Antonia Sanches Ito, Larissa Bail, Fábio André dos Santos, José Carlos Rebuglio Vellosa
Journal: Metabolism (2012)
Follow-Up of a Carcinoid Tumor in the Middle Ear by In-111 Pentetreotide Scintigraphy
Authors: Raúl Martínez-Lázaro, Anabel Cortes-Blanco, Andrés Moreno-Selva, Maribel Blázquez Morote
Journal: Clinical Nuclear Medicine (2007)

Carcinoid tumor of the middle ear is a rare tumor, with only 46 cases reported. Presentation and symptoms are consistent with a middle ear mass and rarely include carcinoid syndrome. After surgical excision, indefinite follow-up has become necessary as authors have recently realized that possible local recurrence or regional metastases may appear in about 20% and 10% of the cases, respectively. Utility of In-111 penteotride scintigraphy for the detection of carcinoid tumors is well known, but its utility for the detection and follow-up of this type of tumor when located in the ear is rarely documented. We report a carcinoid tumor of the middle ear detected by In-111 pentetreotide scintigraphy in the follow-up of a patient with previous surgical excision of this entity.
Aspirin for everyone over 50?: Don't forget aspirin resistance
Authors: Ketan K Dhatariya
Journal: BMJ (2005)

Drug combinations and all cause mortality in heart disease No new insights were gainedEditor-Hippisley-Cox and Coupland conclude that the addition of angiotensin converting enzyme (ACE) inhibitors to combinations of drugs conferred no additional benefit in their study of patients in primary care with ischaemic heart disease. 1 However, such a conclusion should be reached with caution.The drugs were given to the patients with the highest risk of death.A higher percentage of patients who died were treated with ACE inhibitors, and the greatest improvement in risk of death after adjustment for risk factors was seen in the patients treated with these drugs.ACE inhibitors might thus have been given to the patients with the most severe disease in each comorbidity group-for example, to diabetic patients with kidney disease and to patients with the most severe heart failure.Therefore the study can give no indication of the crucial question whether the outcome would have been equally good for the group of 463 patients who probably had the most severe disease and received statins, aspirin, blockers, and ACE inhibitors if they had not been given ACE inhibitors.Replacement of yes or no for comorbidity factors with more discriminating variables, such as presence of microalbuminuria and a severity measure for heart disease, would probably have improved the study.However, this cannot replace the quality of a randomised, placebo controlled study comparing the effect of adding ACE inhibitors to the other study drugs.Therefore the study by Hippisley-Cox and Coupland adds no new knowledge to how patients with ischaemic heart disease in primary care should be treated.
Medical Directors of Life Insurance.
Authors: S. T. McDermith
Journal: JAMA (1896)

Denver, Colo., May 12, 1896. <h3>To the Editor:</h3> —In ourJournalof April 18, mention is made of the annual meeting at Richmond of the "Association of Life Insurance Medical Directors," on April 30 and May 1. Can you inform me who and where are the officers, secretary especially, of the Association?
The scandal of poor medical research
Authors: D G Altman
Journal: BMJ (1994)

We need less research, better research, and research done for the right reasons

What should we think about a doctor who uses the wrong treatment, either wilfully or through ignorance, or who uses the right treatment wrongly (such as by giving the wrong dose of a drug)? Most people would agree that such behaviour was unprofessional, arguably unethical, and certainly unacceptable.

What, then, should we think about researchers who use the wrong techniques (either wilfully or in ignorance), use the right techniques wrongly, misinterpret their results, report their results selectively, cite the literature selectively, and draw unjustified conclusions? We should be appalled. Yet numerous studies of the medical literature, in both general and specialist journals, have shown that all of the above phenomena are common.1 2 3 4 5 6 7 This is surely a scandal.

When I tell friends outside medicine that many papers published in medical journals are misleading because of methodological weaknesses they are rightly shocked. Huge sums of money are spent annually on research that is seriously flawed through the use of inappropriate designs, unrepresentative samples, small samples, incorrect methods …
I. ORGANIZATION AND OBJECTS OF THE MEDICAL RESEARCH BOARD, AIR SERVICE, U. S. ARMY
Authors: YANDELL HENDERSON
Journal: JAMA (1918)

The Medical Research Board was organized early in the autumn of 1917, "to investigate all conditions which affect the efficiency of pilots; to institute and carry out at flying schools or elsewhere such experiments and tests as will determine the ability of pilots to fly in high altitudes; to carry out experiments to provide suitable apparatus for the supply of oxygen to pilots in high altitudes; to act as a standing medical board for the consideration of all matters relating to the physical fitness of pilots." The equipment controlled by the board consists of a large and constantly expanding laboratory for research and teaching at one of the principal eastern flying fields, and of smaller branch laboratories for examining purposes already at work or being organized at twenty other flying fields and ground schools. In the main laboratory, departments have been organized in physiology, cardiovascular functions, psychology, ophthalmology, otology and
Skateboard injuries: preliminary report.
Authors: C Illingworth, A Jay, R Parkin, M Collick, D Noble, V Robson, A Ilsley
Journal: BMJ (1977)

admitted to being overweight at the time of the survey, and 70 had smoked cigarettes most of their adult lives.There was a 2:1 ratio of sedentary to non-sedentary workers.The incidence and episodes of all ischaemic heart disease and myocardial infarction in the cyclists is compared with equivalent age groups in the National Morbidity Survey (NMS) (1971) (see table ).The drawback of comparing NMS figures, which are based on cases reported to GPs, with the questionnaire is that the latter has no details of dead FCOT members before death and the population structure is different.Only a general impression therefore is claimed from these figures.Comparison with a similar group or club of "survivors" would have been more desirable.
Factor XI Deficiency Acquired by Liver Transplantation
Authors: Kevin Clarkson, Brian Rosenfeld, Jeffrey Fair, Andrew Klein, William Bell
Journal: Annals of Internal Medicine (1991)

▪ Factor XI deficiency (the Rosenthal syndrome), an autosomal recessive genetic defect, was transmitted to a patient after orthotopic liver transplantation. The deficiency was manifested by an isolated prolonged activated partial thromboplastin time (aPTT) after surgery. Hematologic evaluation using specific factor analysis revealed an absolute deficiency of factor Xl. Stored serum obtained from the organ recipient before transplantation showed normal factor XI levels. When the liver donor's family was questioned, it was discovered that he was of Ashkenazi Jewish descent and that he had a history of bleeding after dental procedures. Before his death from intracerebral bleeding, he was documented to have an isolated prolonged aPTT value. This case shows that potentially morbid genetic defects can be transmitted by organ transplantation. It also provides evidence confirming that the liver is the only site of factor XI production.
Vancomycin minimum inhibitory concentration, host comorbidities and mortality in Staphylococcus aureus bacteraemia
Authors: N.E. Holmes, J.D. Turnidge, W.J. Munckhof, J.O. Robinson, T.M. Korman, M.V.N. O'Sullivan, T.L. Anderson, S.A. Roberts, S.J.C. Warren, W. Gao, P.D.R. Johnson, B.P. Howden
Journal: Clinical Microbiology and Infection (2013)
Tonsils, Rheumatic Fever and Health Delivery
Authors: Lewis W. Wannamaker
Journal: New England Journal of Medicine (1970)

SINCE the early operative report by Celsus1 in the first century, physicians have searched for rational reasons for removing the tonsils. Few have been found. To a large extent the extirpation of tonsillar tissue continues to be a ritual,2 more akin to a bloodletting rite than to a scientific procedure. The indications for tonsillectomy on which most physicians will agree are cancer and chronic severe obstruction to breathing, which in rare cases may be associated with cor pulmonale.Most other criteria are ill defined and poorly documented. Some complaints such as bed-wetting and convulsions seem to have been safely put . . .
Unlike thyrotropin, thyroid-stimulating antibodies do not activate phospholipase C in human thyroid slices.
Authors: E Laurent, J Van Sande, M Ludgate, B Corvilain, P Rocmans, J E Dumont, J Mockel
Journal: Journal of Clinical Investigation (1991)

The effects of thyroid-stimulating antibodies (TSAb) and of thyrotropin (TSH) were compared, on the generation of cyclic AMP and inositol phosphates (InsP), in human thyroid slices incubated in vitro, and on the Rapoport cyclic AMP bioassay. The TSAb positive sera were obtained from 19 patients with Graves' disease. In 14 experiments with the slices system, TSH significantly increased cyclic AMP accumulation (TSH, 0.03-10 mU/ml) as well as the cyclic AMP-independent inositol trisphosphate (InsP3) generation (TSH, 1-10 mU/ml). In the same 14 experiments, TSAb (0.10-28 mg/ml) enhanced cyclic AMP intracellular levels as expected while they did not induce any InsP accumulation. Even when TSAb increased cyclic AMP levels to the same or higher values as those obtained with TSH concentrations allowing InsP3 generation. TSAb were still unable to activate the phosphatidylinositol-Ca2+ cascade. The patterns of the response curves of TSAb and TSH on cyclic AMP accumulation were different, suggesting that different mechanisms may be involved. In addition, unlike TSH, TSAb were not able to stimulate H2O2 generation, which in human tissue mainly depends on the activation of the phosphatidylinositol-Ca2+ cascade. Immunoglobulins from six additional Graves' patients lacking measurable cyclic AMP-stimulating activity in both slices and cells systems did not activate phospholipase C either. In conclusion, our results show that TSAb do not share all the metabolic actions of TSH on human thyroid tissue. The data provide support for the concept that the pathogenesis of Graves' disease can be fully accounted for by the ability of TSAb to stimulate adenylate cyclase. This work also confirms that TSH activates the cyclic AMP and the phosphatidylinositol cascade by independent pathways in the human thyroid.
PREDICTORS AND MECHANISM OF LESION PROGRESSION AT THE SIDE BRANCH OSTIUM AFTER MAIN VESSEL STENTING: SERIAL INTRAVASCULAR ULTRASOUND ANALYSIS
Authors: Hahn Joo-Yong, Young Bin Song, Jin-Ho Choi, Seung-Hyuk Choi, Sang Hoon Lee, Hyeon-Cheol Gwon
Journal: Journal of the American College of Cardiology (2010)
EARLY HISTORY OF ANESTHESIOLOGY
Authors: A. Frederick Erdmann
Journal: JAMA (1941)

To the Editor:—  A few men are still living who gave anesthetics in the late years of the nineteenth century. I know some personally, among them Dr. Ferguson, living in South Orange, N. J., approaching his ninetieth year; others are out of my sight but in my heart. To bring both the living, our Silver Greys, and the dead who were the pioneers into the ken of that ever increasing host which is the American Society of Anesthetists, Inc., has become my task at the direction of the parent society. Of the three societies which were organized long ago, the London one was absorbed by the British Medical Association, the Scottish one is still active and the American is—well it is growing. But now what of earlier times and the men into whose labors we have entered? If you are an ancestor or an early son please write to me
The Effect of Anthropometric and Socioeconomic Factors on the Racial Difference in Lung Function
Authors: RAIDA I. HARIK-KHAN, JEROME L. FLEG, DENIS C. MULLER, ROBERT A. WISE
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

African-Americans have lower lung function than whites. However, the relative contributions of body habitus and socioeconomic factors are unknown. To address this question, we analyzed data from 1242 white (806 women, 436 men) and 1084 African-American (696 women, 388 men) asymptomatic, nonsmoking adult participants of the third National Health and Nutrition Examination Survey (NHANES III). African-Americans were poorer, had larger FEV1/FVC and body mass index (BMI), but lower sitting height, FEV1 and FVC than whites. Cross-sectional regression analyses using spirometric, anthropometric, and socioeconomic data were performed separately by sex to investigate racial differences in lung function. Sitting height accounted for 35–39% of the race difference in both sexes. Poverty index accounted for about 7.5% and 2.5% of the racial difference in women and men, respectively, whereas the effect of education accounted for about 2% in women and 4.7% in men. With further adjustment for BMI, we could account for only about half of the racial difference in FEV1 and FVC. We conclude that the racial difference in lung function is only partially explained by a shorter upper body segment in African-Americans. Although low socioeconomic indicators are related to lower lung function, they explain only a small proportion of this racial difference.