tbuckley/cabot-search huggingface dataset:
Prolongation of repolarization time by electric field stimulation with monophasic and biphasic shocks in open-chest dogs.
Authors: X H Zhou, S B Knisley, P D Wolf, D L Rollins, W M Smith, R E Ideker
Journal: Circulation Research (1991)

Recent studies suggest that 1) electrically induced fibrillation and defibrillation involve prolongation of refractoriness by the shock in addition to stimulation and 2) biphasic waveforms are more efficient for defibrillation than are comparable monophasic waveforms. The purpose of this study was to compare prolongation of action potential duration at 50% repolarization by monophasic and biphasic shocks during paced rhythm. A floating glass microelectrode was used to record intracellularly from the anterior right ventricular epicardium in seven open-chest dogs. After 10 S1 beats paced at an interval of 350 msec, 5-msec and 2.5-msec monophasic shocks and biphasic shocks, with each phase of 2.5 msec, were given via mesh electrodes on either side of the microelectrode. The shock strength was adjusted so that the shock field, measured from eight extracellular electrodes encircling the microelectrode, was about 5 V/cm. Monophasic and biphasic S2 shocks were given starting with an S1-S2 interval of 120 msec, which was increased in 5-msec steps until an action potential was produced by the S2 shock. Both monophasic and biphasic 5 V/cm shock fields caused significant prolongation of action potential duration. The prolongation of action potential duration increased as the S1-S2 interval increased. This prolongation occurred at shorter S1-S2 intervals for 5-msec monophasic shocks than for biphasic shocks.
Preventing Peanut Allergy through Early Consumption — Ready for Prime Time?
Authors: Rebecca S. Gruchalla, Hugh A. Sampson
Journal: New England Journal of Medicine (2015)

Kids can't take peanut butter to school. Some airlines no longer serve peanuts because of fear of anaphylaxis among passengers. These developments are just the tip of the iceberg as the prevalence of peanut allergy among children continues to increase worldwide, especially in westernized countries. In the United States alone, the prevalence has more than quadrupled in the past 13 years, growing from 0.4% in 1997 to 1.4% in 20081 to more than 2% in 2010.2 Peanut allergy has become the leading cause of anaphylaxis and death related to food allergy in the United States.3 In 2000, largely in response . . .
Preconditioning by Transient Myocardial Ischemia Confers Protection Against Ischemia-Induced Ventricular Arrhythmias in Variant Angina
Authors: Vincenzo Pasceri, Gaetano A. Lanza, Giuseppe Patti, Patrizia Pedrotti, Filippo Crea, Attilio Maseri
Journal: Circulation (1996)

In experimental models, ischemic preconditioning of the heart protects against ischemic damage and ventricular arrhythmias during subsequent coronary occlusion. In this study, we investigated whether protection against ischemic suffering and ischemia-induced arrhythmias may occur after spontaneous transmural ischemia in humans.We performed 24-hour Holter monitoring in 10 patients with variant angina who developed complex ventricular arrhythmias (CVAs, more than five premature ventricular beats per minute or repetitive ventricular arrhythmias) during episodes of ST-segment elevation. A total of 150 episodes of ST-segment elevation were detected on Holter monitoring, 21 (14%) of which showed CVAs. Episodes separated from the previous one by a time interval of < or = 30 minutes or by a time interval of > 30 minutes did not differ in either magnitude or duration of ST-segment elevation, but CVAs occurred more frequently in the second group (3% versus 29%, P < .0001). The time interval from the preceding ischemic episode was longer for the episodes with compared with those without CVAs (197 +/- 275 versus 57 +/- 87 minutes, P < .001), but these two groups of episodes also had similar severities and durations of ST-segment elevation. Finally, when we analyzed 13 clusters of two to six ischemic episodes, CVAs were found much more frequently in the first (92%) than in the last (23%, P = .009) episode of the clusters, while ST-segment elevations were similar (2.1 +/- 1.6 versus 2.2 +/- 1.1 mm) and ischemia durations shorter in the first than in the last episode (3.9 +/- 3.6 versus 6.1 +/- 1.7 minutes, P = .03).Our data indicate that preconditioning by transient ischemia induces a significant protection against ischemia-induced CVAs in patients with variant angina. This beneficial effect was not related to a reduction in either severity or duration of ischemia, suggesting that arrhythmic protection was a direct consequence of preconditioning rather than an epiphenomenon of ischemic protection.
Regulation of cation transport by low doses of glucocorticoids in in vivo adrenalectomized rat colon.
Authors: C P Bastl
Journal: Journal of Clinical Investigation (1987)

A dose response curve for glucocorticoid-induced proximal and distal colonic cation transport in vivo was established in adrenalectomized rats. All doses (0.5-50 nmol/100 g body wt) stimulated sodium absorption. Distal sodium absorption did not saturate at dexamethasone levels that saturate the glucocorticoid receptor but also bind to greater than 35% of aldosterone receptors. Saturation of the pure glucocorticoid response occurred in both segments with RU26988, a synthetic glucocorticoid that does not occupy aldosterone receptors. Maximum velocities for pure glucocorticoid-induced sodium absorption were 15 and 16 mu eq/min per g dry tissue, and Michaelis constants (Km) were 4.2 and 4.6 X 10(-9) mol/liter for proximal and distal colon. Kms are similar to the dissociation constant for the colonic glucocorticoid receptor and too low for significant aldosterone receptor occupancy. Dexamethasone increased sodium absorption significantly within 30 min of injection, suggesting the response is not dependent on new protein synthesis. Similar time and dose responses in proximal and distal colon suggest glucocorticoids stimulate the same pathway in both segments.
Cardiovascular outcomes after kidney–pancreas and kidney–alone transplantation11See Editorial by Langone and Helderman, p. 2035.
Authors: Ennio La Rocca, Paolo Fiorina, Valerio Di Carlo, Ettore Astorri, Claudio Rossetti, Giovanni Lucignani, Ferruccio Fazio, Daniela Giudici, Marco Cristallo, Giuseppi Bianchi, Guido Pozza, Antonio Secchi
Journal: Kidney International (2001)
Clinical and immunological profiles in 17 Japanese patients with drug‐induced pemphigus studied at Kurume University
Authors: K. Yoshimura, N. Ishii, T. Hamada, T. Abe, F. Ono, K. Hashikawa, S. Fukuda, B. Ohyama, H. Koga, R. Sogame, K. Teye, T. Ochiai, H. Nakajima, K. Nakajima, S. Iijima, M. Kanzaki, K. Kojima, T. Nagatani, W. Fujimoto, T. Karashima, T. Nakama, C. Ohata, M. Furumura, D. Tsuruta, T. Hashimoto
Journal: British Journal of Dermatology (2014)

Drug-induced pemphigus (DIP) shows clinical, histopathological and immunological features of pemphigus. However, little is known about immunological profiles in DIP.To characterize clinical and immunological profiles in patients with DIP.We studied 17 Japanese patients with DIP who were treated at Kurume University Hospital or who consulted from other hospitals between 1997 and 2012. Complicated diseases, clinical and histopathological manifestations, responsible drugs and findings in immunofluorescence, enzyme-linked immunosorbent assays (ELISAs), immunoblotting (IB) and prognosis were analysed.Eight of the 17 patients with DIP showed pemphigus foliaceus-like appearance, three showed pemphigus herpetiformis-like appearance, and six showed atypical bullous lesions. Responsible drugs were thiol-containing drugs in 16 patients (bucillamine in nine cases, d-penicillamine in four cases, and cetapril, thiopronine and captopril in one patient each), and a nonthiol drug, sulfasalazine, in one patient. By ELISAs and/or IB analyses, nine patients reacted only with desmoglein 1 (Dsg1), four reacted with Dsg1 and Dsg3, and four showed no specific reactivity. By IB of normal human epidermal extracts, in addition to positive reactivity with Dsg1, four patients with no detectable malignancy showed paraneoplastic pemphigus-like reactivity with the 210-kDa envoplakin and the 190-kDa periplakin. Four cases showed anti-Dsg3 antibodies without mucosal lesions. While 11 cases recovered after discontinuation of the causative drugs, six patients had a very protracted or intractable disease course, and might develop true pemphigus.The present study indicated that the majority of the patients with DIP studied showed a pemphigus foliaceus-type phenotype with anti-Dsg1 autoantibodies, caused by thiol-containing drugs.
Reproductive and morphological condition of wild mink (Mustela vison) and river otters (Lutra canadensis) in relation to chlorinated hydrocarbon contamination.
Authors: L E Harding, M L Harris, C R Stephen, J E Elliott
Journal: Environmental Health Perspectives (1999)

We assessed chlorinated hydrocarbon contamination of mink and river otters on the Columbia and Fraser River systems of northwestern North America, in relation to morphological measures of condition. We obtained carcasses of mink and river otters from commercial trappers during the winters 1994-1995 and 1995-1996. Necropsies included evaluation of the following biological parameters: sex, body mass and length, age, thymus, heart, liver, lung, spleen, pancreas, kidney, gonad, omentum, adrenal gland and baculum masses, baculum length, and stomach contents. Livers were analyzed, individually or in pools, for residues of organochlorine (OC) pesticides, polychlorinated biphenyls (PCBs), dibenzo-p-dioxins, and dibenzofurans. Contaminant levels were relatively low compared to those documented in other North American populations, although they ranged higher than those detected during an earlier survey (1990-1992) of these regional populations. Body condition varied slightly among collection regions, but showed no relationship with contaminant burden. Mink from the upper Fraser River had less fat stores and also had some of the lowest OC contamination levels observed. Similarly, a few individuals with enlarged livers and kidneys had low contaminant levels. Although a few individual animals with gross abnormalities of reproductive systems did not show high levels of contamination, there was a significant negative correlation between total PCB concentrations (as Aroclor 1260) and baculum length in juvenile mink (r = 0.707; p = 0.033; n = 8). The association of juvenile baculum length with eventual reproductive success is unknown, but further characterization of reproductive organ morphology and relationship to contaminants should be undertaken in a larger subset of these populations.
CHRONIC RHEUMATIC BRAIN DISEASE AS A POSSIBLE FACTOR IN THE CAUSATION OF SOME CASES OF DEMENTIA PRÆCOX
Authors: WALTER L. BRUETSCH
Journal: American Journal of Psychiatry (1940)

Nine per cent of dementia præcox patients who were examined at autopsy showed signs of a chronic rheumatic infection, involving the brain as well as the heart valves. The rheumatic alterations in the brain consisted of a recurrent vascular process of an obliterating endarteritic type, affecting in the dementia præcox group mainly the meningeal and cortical vessels with subsequent degeneration in the cortex. The process as a whole has been termed chronic rheumatic brain disease. It evolution occurs in terms of years and decades and not of weeks or months as in the acute period of infection. When lesions develop they are, with rare exceptions, no longer acute and actively inflammatory, but are slowly proliferative. After years of symptomatic quiescence, progression of the disease from the latent stage to subacute activity may take place.
Evaluation of Interval Times From Onset to Reperfusion in Patients Undergoing Endovascular Therapy in the Interventional Management of Stroke III Trial
Authors: Mayank Goyal, Mohammed A. Almekhlafi, Liqiong Fan, Bijoy K. Menon, Andrew M. Demchuk, Sharon D. Yeatts, Michael D. Hill, Thomas Tomsick, Pooja Khatri, Osama O. Zaidat, Edward C. Jauch, Muneer Eesa, Tudor G. Jovin, Joseph P. Broderick
Journal: Circulation (2014)

Background— Meaningful delays occurred in the Interventional Management of Stroke (IMS) III trial. Analysis of the work flow will identify factors contributing to the in-hospital delays. Methods and Results— In the endovascular arm of the IMS III trial, the following time intervals were calculated: stroke onset to emergency department arrival; emergency department to computed tomography (CT); CT to intravenous tissue plasminogen activator start; intravenous tissue plasminogen activator start to randomization; randomization to groin puncture; groin puncture to thrombus identification; thrombus identification to start of endovascular therapy; and start of endovascular therapy to reperfusion. The effects of enrollment time, CT angiography use, interhospital transfers, and intubation on work flow were evaluated. Delays occurred notably in the time intervals from intravenous tissue plasminogen activator initiation to groin puncture (median 84 minutes) and start of endovascular therapy to reperfusion (median 85 minutes). The CT to groin puncture time was significantly shorter during working hours than after. Times from emergency department to reperfusion and groin puncture to reperfusion decreased over the trial period. Patients with CT angiography had shorter emergency department to reperfusion and onset to reperfusion times. Transfer of patients resulted in a longer onset to reperfusion time compared with those treated in the same center. Age, sex, National Institutes of Health Stroke Scale score, and intubation did not affect delays. Conclusions— Important delays were identified before reperfusion in the IMS III trial. Delays decreased as the trial progressed. Use of CT angiography and endovascular treatment in the same center were associated with time savings. These data may help in optimizing work flow in current and future endovascular trials. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00359424.
Divergent effects of ACE-inhibition and calcium channel blockade on NO-activity in systemic and renal circulation in essential hypertension
Authors: L Dijkhorst-Oei
Journal: Cardiovascular Research (1998)

Objective: Nitric oxide is a vasodilating and blood pressure lowering substance. To investigate whether calcium antagonists or angiotensin-converting enzyme (ACE) inhibitors increase vascular nitric oxide activity, we assessed systemic and renal vascular sensitivity to nitric oxide synthase inhibition in hypertensives on and off medication. Methods: Ten essential hypertensive patients, aged 22–51 years, were studied 3 times: ≥4 weeks off medication, after 3 weeks treatment with enalapril 20 mg twice a day and after 3 weeks nifedipine 60 mg/day. Each time, 24-h blood pressure registration was performed, followed by a clearance study to obtain a 3-h dose-response curve for intravenously infused NG-monomethyl-l-arginine (l-NMMA, respectively 0.75, 1.5 and 3.0 mg/kg/h). Results:l-NMMA dose-dependently increased mean arterial pressure with 5±2 mmHg and systemic vascular resistance with 24±5% at maximum dose, whereas cardiac output decreased (all P<0.001). Enalapril and nifedipine treatment decreased blood pressure, while the l-NMMA-induced increase in systemic vascular resistance was potentiated (enalapril: 45±7% and nifedipine: 46±8%; both P<0.01). l-NMMA also dose-dependently decreased renal blood flow by 58±8% at maximum dose (P<0.001), but neither drug potentiated these effects. Conclusion: These results indicate that, in essential hypertensives, antihypertensive therapy with enalapril or nifedipine increases nitric oxide dependency of systemic vascular tone, which may play a role in the blood pressure lowering effect of these drugs. However, this phenomenon cannot be observed in the renal circulation, suggesting a different regulation of endothelium-dependent vasomotion in the hypertensive kidney.
DIABETES MELLITUS, MYOCARDIAL REPERFUSION AND OUTCOME IN PATIENTS WITH ACUTE ST-ELEVATION MYOCARDIAL INFARCTION TREATED WITH PRIMARY ANGIOPLASTY; INSIGHTS FROM HORIZONS AMI
Authors: Sorin J. Brener, Roxana Mehran, Ovidiu Dressler, Ecaterina Cristea, Gregg Stone
Journal: Journal of the American College of Cardiology (2012)
A third of those in need of antiretrovirals in poor countries can now get them
Authors: J. Zarocostas
Journal: BMJ (2010)

Last year saw important gains in expanding access to HIV treatment and care in several low and middle income countries, but interventions need to be scaled up to help millions of people access antiretrovirals, says a new global report.

At the end of 2009 5.25 million people with HIV in low and middle income countries received antiretroviral treatment, a rise of 30% from December 2008, or more than 1.2 million people, says the report by the World Health Organization, UNAIDS, and Unicef.

Despite these gains, the heads of the three agencies warn in a foreword to the report: “More than five million people needing antiretroviral therapy do not have access to it. Far too many people access health services in late stages of HIV disease …
Nicotine exposure and bronchial epithelial cell nicotinic acetylcholine receptor expression in the pathogenesis of lung cancer
Authors: John D. Minna
Journal: Journal of Clinical Investigation (2003)

Nonstandard abbreviations used: nicotinic acetylcholine receptor (nAchR); acetylcholine (Ach); N′Nitrosonornicotine (NNN); 4(methylnitrosamino)-1-(3-pyridyl)-1butanone (NNK); normal human bronchial epithelial cell (NHBE); small airway epithelial cell (SAEC); protein kinase B (PKB); B cell lymphoma 2 (BLC2); trans-retinoic acid (RA); retinoic acid receptor (RAR); Janus kinase 2 (JAK2); mitogen-activated protein kinase (ERK); retinoid X
PTU-001 Overuse Of Proton Pump Inhibitors And Strategies To Reduce Inappropriate Prescribing
Authors: C Owen, DJB Marks, P Panesar
Journal: Gut (2014)

<h3>Introduction</h3> Proton pump inhibitors (PPIs) are widely used but commonly over-prescribed.<sup>1</sup> A range of adverse effects are associated with their use, including susceptibility to C. difficile infection, fractures, pneumonia and electrolyte disturbances.<sup>2</sup> <h3>Methods</h3> We investigated the extent and appropriateness of PPI prescribing at a university teaching hospital, and the impact on this of guideline implementation alongside formal teaching of junior doctors. A point-prevalence survey of PPI prescribing for in-patients across medical and surgical specialties was performed. Data collected included PPI prescription, whether this was initiated in hospital or the community, whether an evidenced-based indication was identifiable, and if the prescriber had documented an intended duration for its use. A local guideline was developed in line with current evidence, and national and international guidance. This was circulated to all prescribers by email and the hospital intranet, as well as face-to-face presentation to junior doctors alongside discussion around potential adverse effects. A further point-prevalence survey was undertaken after implementation. <h3>Results</h3> A total of 274 patients were included in the first point-prevalence survey, and 264 in the second cycle. Initially, 52.7% of inpatients were prescribed a PPI; of these, 38.1% were commenced in hospital. An appropriate indication was documented in 34.7% and duration in 8.2%. Following introduction of a guideline and a programme of education, the proportion of inpatients receiving PPI therapy fell to 40.8% (p = 0.008), of which 28.4% were started in hospital (p = 0.08), 38.5% had an appropriate indication recorded, and 4.6% the duration. <h3>Conclusion</h3> PPI prescribing rates among inpatients are high, and frequently not evidenced-based. There is also lack of consideration given to review of therapy and limiting provision to short courses. A combined approach of a focused guideline and educational strategies can reduce inappropriate over prescribing, but had restricted impact on the quality of documentation and specification of duration of therapy. <h3>References</h3> Eid S <i>et al</i>. Patterns and predictors of proton pump inhibitor overuse among academic and non-academic hospitals. <i>Intern Med</i> 2010;49:2561–2568 Abraham NS. Proton pump inhibitors: potential adverse effects. <i>Curr Opin Gastroenterol</i> Nov;2012;28(6):615–20 <h3>Disclosure of Interest</h3> None Declared.
Dynamic measurements of the acute and chronic effects of lysosomotropic agents on hepatocyte lysosomal pH using flow cytometry
Authors: Brent M. Myers, Pamela S. Tietz, James E. Tarara, Nicholas F. Larusso
Journal: Hepatology (1995)

Previous investigators measuring the pH of lysosomes have used digitized video microscopy (DVM) in freshly isolated or cultured cells. Although useful, this technique is time consuming, requires the use of an image analysis system, and is limited by the fact that measurements can be made in only a relatively small number of cells. The aim of this study was to develop and initially apply a technique using flow cytometry to make dynamic measurements of lysosomal pH in a large number of living hepatocytes. Rats were injected intraperitoneally with fluorescein isothiocyanate-dextran (FITC-Dex), a pH-sensitive fluorescent probe that is sequestered into lysosomes. Hepatocytes were isolated 16 hours after injection by collagenase perfusion. Lysosomal pH was measured in 20,000 hepatocytes per animal using flow cytometry with excitation at 488 nm and emission at 530 nm (pH sensitive) and 585 nm (pH insensitive). A standard curve of pH versus the 530/585 nm ratio was generated with FITC-Dex-loaded hepatocytes by equilibrating intralysosomal pH with extracellular pH using ionophores and metabolic inhibitors. The acute effects of chloroquine and methylamine were determined by exposing isolated hepatocytes to these lysosomotropic agents. The effect of chronic administration of chloroquine and Triton WR-1339 (Rutger Chemical, Inc., Irvington, NJ) on lysosomal pH was also measured. Intralysosomal pH was 4.67 + 0.02, nearly identical to the value 4.70 + 0.05 previously measured by us using DVM. Both chloroquine and methylamine caused both rapid (< 1 minute), major (0.5 to 2.0 pH units), and dose-dependent increases in lysosomal pH as well as changes in lysosome morphology.(ABSTRACT TRUNCATED AT 250 WORDS)
Doctors and nuclear war
Authors: J H Humphrey, J W Boag, L. Brent, E Easson, R Hoffenberg, M. Irving, A Jacobs, B. Knight, J A Loraine, I. McLintock, T W Meade, J L Mongar, M. Morgan, C R Pennington, D Peters, M. Raff, R. Roaf, S. M. Roth, S. Shuster, A. Smith, R B Welbourn
Journal: BMJ (1983)
A unique cell surface antigen identifying lymphoid malignancies of B cell origin.
Authors: L M Nadler, J Ritz, R Hardy, J M Pesando, S F Schlossman, P Stashenko
Journal: Journal of Clinical Investigation (1981)

A monoclonal antibody (anti-B1) specific for a unique B cell surface differentiation antigen was used to characterize the malignant cells from patients with leukemias or lymphomas. All tumor cells from patients with lymphomas or chronic lymphocytic leukemias, bearing either monoclonal kappa lambda light chain, expressed the B1 antigen. In contrast, tumor cells from T cell leukemias and lymphomas or acute myeloblastic leukemia were unreactive. Approximately 50% of acute lymphoblastic leukemias (ALL) of non-T origin and 50% of chronic myelocytic leukemia in blast crisis were also anti-B1 reactive. moreover, 21 of 28 patients with the common ALL antigen (CALLA) positive form of ALL were anti-B1 positive, whereas 0 of 13 patients with CALLA negative ALL were reactive. These observations demonstrate that an antigen present on normal B cells is expressed on the vast majority of B cell lymphomas and on approximately 75% of CALLA positive ALL, suggesting that these tumors may share a common B cell lineage.