tbuckley/cabot-search huggingface dataset:
EVOLUTION OF GIRLS.
Authors: HARRIET E. GARRISON
Journal: JAMA (1896)

The question whether man has ascended from the monkey or descended from "a little lower than the angels" does not matter in the present discussion; also whether women have passed to a higher or lower plane in the evolution of our higher woman; whether it is a higher sphere to wield the keen, logical brain of a Maria Mitchell or to be the mother of a host of well trained sons as Cornelia, is not pertinent to the present subject. For the reason that popular opinion, before which we all fall prostrate, says woman's brain, whatever its capacity, must be made to hold a certain amount of book lore which we call an education. Sometimes when we have this erudition applied we think with the poet, "Knowledge comes, but wisdom lingers." "Go on to perfection" is the motto written above every scientific laboratory door; and one of the most weighty
Regadenoson Versus Dipyridamole Hyperemia for Cardiac PET Imaging
Authors: Nils P. Johnson, K. Lance Gould
Journal: JACC. Cardiovascular imaging (2015)

The goal of this study was to compare regadenoson and dipyridamole hyperemia for quantitative myocardial perfusion imaging.Regadenoson is commonly used for stress perfusion imaging. However, no study in nuclear cardiology has employed a paired design to compare quantitative hyperemic flow from regadenoson to more traditional agents such as dipyridamole. Additionally, the timing of regadenoson bolus relative to tracer administration can be expected to affect quantitative flow.Subjects underwent 2 rest/stress cardiac positron emission tomography scans using an Rb-82 generator. Each scan employed dipyridamole and a second drug in random sequence, either regadenoson according to 5 timing sequences or repeated dipyridamole. A validated retention model quantified absolute flow and coronary flow reserve.A total of 176 pairs compared regadenoson (126 pairs, split unevenly among 5 timing sequences) or repeated dipyridamole (50 pairs). The cohort largely had few symptoms, only risk factors, and nearly normal relative uptake images, with 8% typical angina or dyspnea, 20% manifest coronary artery disease, and a minimum quadrant average of 80% (interquartile range: 76% to 83%) on dipyridamole scans. Hyperemic flow varied among regadenoson timing sequences but showed consistently lower stress flow and coronary flow reserve compared with dipyridamole. A timing sequence most similar to the regadenoson package insert achieved about 80% of dipyridamole hyperemia, whereas further delaying radiotracer injection reached approximately 90% of dipyridamole hyperemia. Because of the small numbers of pairs for each regadenoson timing protocol and a paucity of moderate or large perfusion defects, we did not observe a difference in relative uptake.With the standard timing protocol from the package insert, regadenoson achieved only 80% of dipyridamole hyperemia quantitatively imaged by cardiac positron emission tomography using Rb-82. A nonstandard protocol using a more delayed radionuclide injection after the regadenoson bolus improved its effect to 90% of dipyridamole hyperemia.
Viral antibody studies in pancreatic disease.
Authors: P Capner, R Lendrum, D J Jeffries, G Walker
Journal: Gut (1975)

Viral studies were performed on sera from 54 patients with recent acute pancreatitis, 10 with recurrent acute pancreatitis, seven with chronic pancreatitis, and 10 with pancreatic carcinoma, and on sera from 81 age- and sex-matched controls. In 29 of the acute pancreatitis patients from whom paired sera were obtained no convincing evidence of recent viral infection was found. A higher incidence of raised antibody titres against Coxsackie B3 and B4 was observed in the group of acute pancreatitis patients compared with their controls. The possible signficance of these observations and their relationship to the aetiology of the pancreatitis and to other immunological findings are discussed.
Mast cell numbers in incisional wounds in rat skin as a function of distance, time and treatment
Authors: M.A. PERSINGER, PATRICIA LEPAGE, J.-P. SIMARD, G.H. PARKER
Journal: British Journal of Dermatology (1983)

The dynamic changes in skin mast cell (MC) numbers around incised wounds were studied, using experimental designs amenable to multiple analyses of variance. Sixty-four Wistar albino rats were shaved in the interscapular region, wounded or not wounded, and then killed 2 or 10 days later. During this period, the rats were exposed continually to a cold (2 degrees C) or control (20 degrees C) climate and treated daily over the shaved region with either tap water or a weak sulphuric acid (pH 3.5) solution. The MCs within five adjacent fields of the wound or the control reference and within the superficial and deep halves of the skin were counted (at x 400). The greatest decrease in MC numbers occurred within about 700 microns of the wound. Whereas the paucity of MCs within the wound region was evident at 2 days, near-normal levels were achieved by day 10. Cold exposure produced little effect, but MCs responded differently to the water and acid treatments as a function of distance and skin depth.
Grape juice causes endothelium-dependent relaxation via a redox-sensitive Src- and Akt-dependent activation of eNOS
Authors: E ANSELM, M CHATAIGNEAU, M NDIAYE, T CHATAIGNEAU, V SCHINIKERTH
Journal: Cardiovascular Research (2006)

An enhanced endothelial formation of nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF), is thought to contribute to the protective effect of moderate consumption of red wine on coronary diseases. The present study has characterized endothelium-dependent relaxations to Concord grape juice (CGJ), a non-alcoholic rich source of grape-derived polyphenols, in the coronary artery.Porcine coronary artery rings were suspended in organ chambers for the measurement of changes in isometric tension in the presence of indomethacin. NO formation was assessed by electron spin resonance spectroscopy, and the phosphorylation of Src, Akt and endothelial NO synthase (eNOS) by Western blot analysis in cultured endothelial cells.Endothelium-dependent relaxations to CGJ were slightly but significantly reduced by L-NA, not affected by charybdotoxin (CTX) plus apamin (APA, two inhibitors of EDHF-mediated responses) whereas the combination of L-NA, CTX plus APA reduced maximal relaxation to about 50%. In the presence of CTX plus APA, relaxations to CGJ were markedly reduced by the membrane permeant mimetic of superoxide dismutase (SOD), MnTMPyP, the membrane permeant analogue of catalase polyethyleneglycol-catalase (PEG-catalase), PP2, an inhibitor of Src kinase, and by wortmannin, an inhibitor of the PI3-kinase. CGJ stimulated the formation of reactive oxygen species and the N(omega)-nitro-L-arginine-, PP2- and wortmannin-sensitive formation of NO in endothelial cells. The formation of NO was associated with a redox-sensitive and time-dependent phosphorylation of Src, Akt and eNOS.CGJ induces endothelium-dependent relaxations of coronary arteries, which involve a NO-mediated component and also, to a minor extent, an EDHF-mediated component. In addition, CGJ-induced NO formation is due to the redox-sensitive activation of Src kinase with the subsequent PI3-kinase/Akt-dependent phosphorylation of eNOS.
SEROTOXIN
Authors: James W. Jobling, William Petersen
Journal: The Journal of Experimental Medicine (1914)

1. Sera from which the protective lipoids (unsaturated fatty acids) have been removed are toxic for the homologous animal. 2. The toxicity is due to three factors: (a) an alteration in the mechanism of coagulation, with resulting intravascular coagulation; (b) the exposure of the native serum proteins; (c) the formation of toxic split products (primary proteoses) by autolysis. 3. A definite maximum of toxicity can be determined, with a final stage of atoxicity due to continued autolysis. 4. Hirudin and sodium citrate do not protect animals. 5. Heating to 70 degrees C. destroys, or greatly lessens, the toxicity of the serotoxin, although the isolated proteoses are toxic after boiling. 6. The return of the extracted lipoids (saponified) neutralizes the toxicity. 7. Unsaturated soaps also neutralize the toxicity. 8. Sublethal doses produce extreme prostration, marked fall in body temperature, no eosinophilia, and an increase of antitrypsin. 9. Sublethal doses of rapidly prepared chloroform sera cause a decrease in coagulation time; sublethal doses of autolyzed sera cause an increase in coagulation time. 10. Previously injected animals are more resistant (increased antiferments). 11. Iodized animals are less resistant (decreased antiferments).
Immunoglobulin and complement deposits in the skin in inflammatory facial dermatoses—an immunofluorescence study
Authors: E. ABELL, M. M. BLACK, R. MARKS
Journal: British Journal of Dermatology (1974)

Biopsy material from ninety‐one cases of inflammatory facial dermatoses was stained by the direct immunofluorescence method. The presence of immunoglobulins and complement in a distinct basement membrane band was seen only in lupus erythematosus. Negative results were found in thirty five cases of rosacea.
Similarities between early and delayed afterdepolarizations induced by isoproterenol in canine ventricular myocytes
Authors: P Volders
Journal: Cardiovascular Research (1997)

Objectives: This study aims at clarifying the role of cellular Ca2+ overload and spontaneous sarcoplasmic reticulum (SR) Ca2+ release in the generation of early afterdepolarizations (EAD) by isoproterenol. The involvement of a Ca2+-activated membrane current in isoproterenol-induced EAD is investigated. Methods: Membrane potential and contraction (an indicator of SR Ca2+ release) were recorded in canine left ventricular myocytes at pacing cycle lengths (CL) of 300–4000 ms. Threshold concentration for EAD was 20–50 nmol/l isoproterenol. Ni2+ (2.0–5.0 mmol/l) was used at normal and high (5.4 mmol/l) [Ca2+]o to examine the role of Ca2+ current and/or Na+–Ca2+ exchange (INa–Ca) in EAD. Results: In all cells delayed afterdepolarizations (DAD) appeared during isoproterenol. In most (≈70%) cells EAD were also generated, which were fast-pacing dependent, occurring only at CL of 400–1000 ms. EAD were always initiated by a delay in repolarization. Early aftercontractions preceded the EAD upstrokes, often occurring without them. They coincided with the initial delays in repolarization. During treatment with isoproterenol, Ni2+ and high [Ca2+]o, EAD and DAD were suppressed despite the continued presence of early and delayed aftercontractions. Conclusions: Our data indicate that β-adrenergic EAD share a common ionic mechanism with DAD in terms of cellular Ca2+ overload and spontaneous SR Ca2+ release. β-Adrenergic EAD consist of two phases: (1) a conditional phase coinciding with the onset of an early aftercontraction, often followed by (2) an EAD upstroke. A Ca2+-activated membrane current, probably INa–Ca, is necessary, at least for the initiation of these EAD.
Effect of immunomodulatory therapies in patients with pandemic influenza A (H1N1) 2009 complicated by pneumonia
Authors: Diego Viasus, José Ramón Paño-Pardo, Elisa Cordero, Antoni Campins, Francisco López-Medrano, Aroa Villoslada, Maria C. Fariñas, Asunción Moreno, Jesús Rodríguez-Baño, José Antonio Oteo
Journal: Journal of Infection (2011)
NICE guidance on insulin pumps is not without drawbacks
Authors: M. Press, J. Holland, R. Miller, D. Kunka, P. Cream
Journal: BMJ (2009)

Guidance on insulin pumps from the National Institute for Health and Clinical Excellence (NICE) recommends that such treatment should be started only by a trained specialist team providing structured education programmes.1

One of our young patients whose type 1 diabetes is managed with an insulin pump bent her insulin catheter while …
Epiphysial Fracture of the Proximal Humerus
Authors: Otto E. Aufranc
Journal: JAMA (1970)

Dr. Stuart Cope: The patient is a 13-year-old boy, a junior high school student interested in athletics. He plays on the varsity football, basketball, and golf teams. He was playing sandlot football when he injured his left shoulder. The mechanism of injury was a fall backward on outstretched hand and elbow. He was brought to the emergency room immediately after injury, complaining only of pain in the left shoulder. Examination revealed no neurovascular deficits. X-rays revealed a displaced fracture of the proximal humeral epiphysis through the plate with a fragment off the diaphysis attached to the epiphysis (Fig 1). <h3>Discussion</h3> Dr. Jones: Pertinent to this history and description of lack of neurovascular deficits, additional important information may be obtained by examination of the injured shoulder through palpation and inspection which can be helpful in planning treatment. A portion of this examination should be made with the patient sitting in a
Experts Look for Ways to Lessen Impact of Drug Shortages and Discontinuations
Authors: Tracy Hampton
Journal: JAMA (2007)

LIVING WITH A DISEASE CAN BE CHALlenging, but for some patients this challenge can be heightened if an effective drug used to treat their condition is not available. Drugs have been discontinued or are in short supply due to manufacturing problems, plant shutdowns, or a lack of a strong market for a particular medication. They also may be unavailable because they are too costly and are not covered by medical insurance. “In 2000, we started to see more and more drug shortages for a variety of reasons,” said Erin Fox, PharmD, a drug information specialist at the University of Utah, in Salt Lake City. In response to this growing problem, experts are working to provide patients with equally effective alternatives when much-needed agents are not available.
The Serum- and Glucocorticoid-Inducible Kinase Sgk-1 Is Involved in Pulmonary Vascular Remodeling
Authors: Rachida S. BelAiba, Talija Djordjevic, Steve Bonello, Ferruh Artunc, Florian Lang, John Hess, Agnes Görlach
Journal: Circulation Research (2006)

The stress-responsive serum- and glucocorticoid-inducible kinase Sgk-1 is involved in osmoregulation and cell survival and may contribute to fibrosis and hypertension. However, the function of Sgk-1 in vascular remodeling and thrombosis, 2 major determinants of pulmonary hypertension (PH), has not been elucidated. We investigated the role of Sgk-1 in thrombin signaling and tissue factor (TF) expression and activity in pulmonary artery smooth muscle cells (PASMC). Thrombin increased Sgk-1 activity and mRNA and protein expression. H 2 O 2 similarly induced Sgk-1 expression. Antioxidants, dominant-negative Rac, and depletion of the NADPH oxidase subunit p22phox diminished thrombin-induced Sgk-1 expression. Inhibition of p38 mitogen-activated protein kinase, phosphatidylinositol 3-kinase, and phosphoinositide-dependent kinase-1 prevented thrombin-induced Sgk-1 expression. Thrombin or Sgk-1 overexpression enhanced TF expression and procoagulant activity, whereas TF upregulation by thrombin was diminished by kinase-deficient Sgk-1 and was not detectable in fibroblasts from mice deficient in sgk-1 (sgk1 −/− ). Similarly, dexamethasone treatment failed to induce TF expression and activity in lung tissue from sgk1 −/− mice. Transcriptional induction of TF by Sgk-1 was mediated through nuclear factor κB. Finally, Sgk-1 and TF proteins were detected in the media of remodeled pulmonary vessels associated with PH. These data show that thrombin potently induces Sgk-1 involving NADPH oxidases, phosphatidylinositol 3-kinase, p38 mitogen-activated protein kinase, and phosphoinositide-dependent kinase-1, and that activation of nuclear factor κB by Sgk-1 mediates TF expression and activity by thrombin. Because enhanced procoagulant activity can promote pulmonary vascular remodeling, and Sgk-1 and TF were present in the media of remodeled pulmonary vessels, this pathway may play a critical role in vascular remodeling in PH.
Asia's Ascent — Global Trends in Biomedical R&amp;D Expenditures
Authors: Justin Chakma, Gordon H. Sun, Jeffrey D. Steinberg, Stephen M. Sammut, Reshma Jagsi
Journal: New England Journal of Medicine (2014)

In recent years, industry has reduced its investment in U.S. biomedical research and development by billions of dollars, while increasing investment in Asia–Oceania. Thus, boosting U.S. government funding alone may be inadequate for retaining long-term R&D leadership.
Transfusion Threshold of 7 g per Deciliter — The New Normal
Authors: Paul C. Hébert, Jeffrey L. Carson
Journal: New England Journal of Medicine (2014)

Holst and colleagues1 now provide definitive evidence in the Journal that a restrictive approach to blood transfusion not only reduced blood use by half but also did not cause harm to 998 critically ill patients with septic shock. It has been 15 years since the publication of the results of the Transfusion Requirements in Critical Care (TRICC) trial in the Journal.2 In that Canadian Critical Care Trial Group study, 838 critically ill patients were randomly assigned to receive blood transfusions on the basis of a threshold of 7 g per deciliter or 10 g per deciliter while also agreeing . . .
THE ABSORPTION OF FAT IN PARTIALLY, AND IN COMPLETELY DEPANCREATIZED DOGS
Authors: Charles W. McClure, Beth Vincent, Joseph H. Pratt
Journal: The Journal of Experimental Medicine (1917)

It was found that dogs with a subcutaneous transplant secreting and discharging pancreatic juice externally absorbed no more fat than dogs in which the pancreatic remnant was undergoing rapid atrophy and sclerosis. Hence, the condition of the pancreatic tissue remaining in the body does not influence the amount of fat absorbed by the intestine. The absorption of fat by the intestinal mucous membrane is always markedly disturbed when the pancreatic secretion is excluded from the intestine. After the complete removal of all pancreatic tissue from an animal, the absorption of considerable amounts of fat can still take place.
Prothrombin complex concentrates in emergency bleeding disorders
Authors: George M. Rodgers
Journal: American Journal of Hematology (2012)

The use of prothrombin complex concentrates (PCCs), a heterogeneous combination of coagulation factors and counterbalancing inhibitor components, has broadened in recent years beyond single-factor replacement in conditions such as hemophilia B, to encompass emergency reversal of anticoagulation secondary to oral vitamin K antagonists, ie, warfarin therapy. PCCs also have been studied in other bleeding disorders, such as surgery-related and trauma-related bleeding. This review provides an updated examination of the differences among PCC formulations, their potential role in the management of bleeding disorders, and the primary safety issues affecting their use. Am. J. Hematol. 2012. © 2012 Wiley Periodicals, Inc.
NHS "pays twice" for patients at walk-in centres who are registered elsewhere, study finds
Authors: G. Iacobucci
Journal: BMJ (2013)

NHS commissioners in England believe that they are paying twice for patients who attend walk-in centres, as most are already registered with a general practice elsewhere that is getting paid for their care, the health sector regulator Monitor has concluded.

Monitor was looking into the recent closures of more than 50 of the walk-in centres set up under the previous Labour government, including many of the so called Darzi centres set up by the former health minister Ara Darzi to improve access and choice.1

The preliminary findings of Monitor’s study found that only 185 of the 238 walk-in centres opened in the past decade were still operating: 135 that were GP led and 50 that were nurse led.2

The regulator concluded that the closures may have worsened …
False Aneurysm of the Pulmonary Artery with Peripheral Venous Thrombosis
Authors: G. M. Kirk, R. M. E. Seal
Journal: Thorax (1964)

Aneurysms of the pulmonary artery are usually of its extrapulmonary portion (Boyd and Mc- Gavack, 1939; Deterling and Clagett, 1947).Intrapulmonary aneurysms are less common, and, when present, are usually mycotic.A rare association of aneurysms of medium- sized branches of the pulmonary artery, venous thrombosis of the legs, and cerebral venous sinus thrombosis as part of a systemic illness has been described (Pirani, Ewart, and Wilson, 1949; Hughes and Stovin, 1959).Pirani et al. (1949) thought the process in the pulmonary artery was mycotic from infected emboli originating in the leg veins.Hughes and Stovin (1959) also asso- ciated the pulmonary aneurysm with embolism of the pulmonary vessel in the presence of abnormal bronchial arteries.This case report is of a similar triad, leg vein thrombosis, sagittal sinus thrombosis, an aneurysm of a branch of the left superior pulmonary artery, and, in addition, an aneurysm of a systemic artery.We suggest that these lesions are due to a 'collagen disease'.CASE REPORT A.J., a man of 29 years, was well until January
Geographic Isolation and the Risk for Chronic Obstructive Pulmonary Disease–Related Mortality
Authors: Thad E. Abrams, Mary Vaughan-Sarrazin, Vincent S. Fan, Peter J. Kaboli
Journal: Annals of Internal Medicine (2011)

Background: Little is known about the possible differences in outcomes between patients with chronic obstructive pulmonary disease (COPD) who live in rural areas and those who live in urban areas of the United States. Objective: To determine whether COPD-related mortality is higher in persons living in rural areas, and to assess whether hospital characteristics influence any observed associations. Design: Retrospective cohort study. Setting: 129 acute care Veterans Affairs hospitals. Patients: Hospitalized patients with a COPD exacerbation. Measurements: Patient rurality (primary exposure); 30-day mortality (primary outcome); and hospital volume and hospital rurality, defined as the mean proportion of hospital admissions coming from rural areas (secondary exposures). Results: 18 809 patients (71% of the study population) lived in urban areas, 5671 (21%) in rural areas, and 1919 (7%) in isolated rural areas. Mortality was increased in patients living in isolated rural areas compared with urban areas (5.0% vs. 3.8%; P = 0.002). The increase in mortality associated with living in an isolated rural area persisted after adjustment for patient characteristics and hospital rurality and volume (odds ratio [OR], 1.42 [95% CI, 1.07 to 1.89]; P = 0.016). Adjusted mortality did not seem to be higher in patients living in nonisolated rural areas (OR, 1.09 [CI, 0.90 to 1.32]; P = 0.47). Results were unchanged in analyses assessing the influence of an omitted confounder on estimates. Limitations: The study population was limited to mostly male inpatients who were veterans. Results were based on administrative data. Conclusion: Patients with COPD living in isolated rural areas of the United States seem to be at greater risk for COPD exacerbation–related mortality than those living in urban areas, independent of hospital rurality and volume. Mortality was not increased for patients living in nonisolated rural areas. Primary Funding Source: U.S. Department of Veterans Affairs.
BMA meeting: GP argues that PCTs have failed to organise adequate out of hours care
Authors: N. Hawkes
Journal: BMJ (2010)

Primary care trusts (PCTs) have failed in the task of organising out of hours care, a GP has told the BMA Annual Representatives Meeting in Brighton, as a motion was passed unanimously recommending that doctors employed from outside the UK are required to work to the same conditions as UK based doctors.

Dr Peter Holden, a Derbyshire GP and one of the negotiators of the 2004 GPs’ contract that placed responsibility for organising out of hours care on PCTs, said that they had failed to rise to the challenge. He was proposing a motion arising from the case of David Gray, …