tbuckley/cabot-search huggingface dataset:
Sodium nitroprusside does not influence tissue oxygen extraction capabilities during a critical reduction in oxygen delivery
Authors: H. Zhang, D. N. Nguyen, H. Spapen, M. Moock, F. Maciel, J.-L. Vincent
Journal: Cardiovascular Research (1995)

By its regulating effects on blood vessel tone, nitric oxide (NO) may play an important role in the coupling of oxygen delivery (DO2) to metabolic rate. We reasoned that if endogenous NO synthesis is an important modulator of oxygen extraction ratio (O2ER), then administration of a NO donor will alter oxygen extraction capabilities during a fall in blood flow. We studied the effects of the NO donor, nitroprusside, on the relationship between DO2 and oxygen uptake (VO2) during an acute reduction in DO2 induced by cardiac tamponade. Twenty-one healthy, anaesthetised, mechanically ventilated dogs were randomly divided into 3 groups. Group 1 (n = 7) served as control; Groups 2 and 3 were given sodium nitroprusside at 1.0 microgram/kg.min (n = 7), and 2.5 micrograms/kg.min intravenously (n = 7), respectively. All animals were given normal saline i.v. at a rate of 20 ml/kg.h throughout the study. Cardiac tamponade was induced by bolus injections of normal saline into the pericardial space. In the control animals the critical DO2 (DO2crit) was found at 10.1 +/- 1.5 ml/kg.min and critical O2ER (O2ERcrit) at 63.3 +/- 10.9%. Nitroprusside at the lower dose decreased systemic vascular resistance but did not significantly influence arterial pressure, cardiac output, DO2 or VO2; neither DO2crit nor O2ERcrit was altered (9.3 +/- 2.9 ml/kg.min and 70.4 +/- 20.9%). Nitroprusside at the higher dose induced significant decreases in mean arterial pressure and systemic vascular resistance, but had no significant effect on cardiac output. DO2crit (9.2 +/- 2.0 ml/kg.min) and O2ERcrit (59.8 +/- 13.2%) were similar to the control group.(ABSTRACT TRUNCATED AT 250 WORDS)
Prophylactic Internal Fixation of Secondary Neoplastic Deposits in Long Bones
Authors: M. Fidler
Journal: BMJ (1973)

The notes and radiographs of 19 patients who had pathological fractures of long bones due to secondary neoplastic deposits were reviewed. Involvement of over half of the cortex is recommended as an indication for prophylactic internal fixation to prevent the development of a pathological fracture. Eight patients were treated successfully in this way. A notable secondary effect of prophylactic internal fixation was the considerable reduction in pain at the site of the lesion.
Rifampicin reduces effectiveness and bioavailability of prednisolone.
Authors: W A McAllister, P J Thompson, S M Al-Habet, H J Rogers
Journal: BMJ (1983)

Rifampicin is an inducer of hepatic drug metabolising enzymes. This results in interactions with several drugs including oral anticoagulants, hypoglycaemics, and contraceptives. Concurrent treatment with prednisolone and rifampicin is given when tuberculosis coexists with a disease that is sensitive to steroids, when the diagnosis is uncertain, or occasionally in the treatment of severe tuberculosis. Two patients with respiratory disease were treated with both drugs: their condition improved considerably after rifampicin was withdrawn. Seven patients were then studied to assess the effect of rifampicin on the pharmacokinetics of prednisolone. Overall, rifampicin increased the plasma clearance of prednisolone by 45% and reduced the amount of drug available to the tissues (area under the plasma concentration time curve) by 66%. The effectiveness of prednisolone may be considerably reduced when rifampicin and prednisolone are used in combination.
Automatic Arrhythmia Identification Using Analysis of the Atrioventricular Association
Authors: Mohan Nair, Nadir Saoudi, Daniel Kroiss, Brice Letac
Journal: Circulation (1997)

Background Atrioventricular association is a key criterion for arrhythmia diagnosis. Its use in a defibrillator should significantly reduce the incidence of inappropriate shocks. Therefore, we evaluated the diagnostic accuracy of an algorithm that uses dual-chamber sensing and analysis of atrioventricular association to discriminate ventricular from supraventricular arrhythmias in a prototype of an implantable defibrillator. Methods and Results The algorithm performed a stepwise analysis of arrhythmias. The rhythm was first classified on the basis of cycle lengths. Each episode was then classified as supraventricular or ventricular in origin on the basis of the stability of cycle lengths and atrioventricular association. This algorithm was evaluated in 156 episodes of induced sustained tachycardias. Eighty-nine tachycardias were taken from the Ann Arbor electrogram library; the others were recorded in 50 patients during electrophysiological studies. The atrial and ventricular signals were stored on an external recorder and then injected into an external prototype of a defibrillator system. The algorithm correctly diagnosed 96% of ventricular tachycardia episodes, 100% of ventricular fibrillation episodes, and 92% of double-tachycardia episodes. The mean detection time for ventricular tachycardia was 2.6±0.8 seconds, and for ventricular fibrillation, it was 2.1±0.4 seconds. The positive predictive values for the diagnoses of atrial fibrillation and atrial flutter were 92% and 86%, respectively. For ventricular tachycardia and ventricular fibrillation, the values were 95% and 100%, respectively. Conclusions Analysis of atrioventricular association promotes reliable differentiation between ventricular and supraventricular tachycardias and should enhance the diagnostic capabilities of implantable defibrillators.
Pathogen-Derived Effectors Trigger Protective Immunity via Activation of the Rac2 Enzyme and the IMD or Rip Kinase Signaling Pathway
Authors: Laurent Boyer, Lorin Magoc, Stephanie Dejardin, Michael Cappillino, Nicholas Paquette, Charlotte Hinault, Guillaume M. Charriere, W.K. Eddie Ip, Shannon Fracchia, Elizabeth Hennessy, Deniz Erturk-Hasdemir, Jean-Marc Reichhart, Neal Silverman, Adam Lacy-Hulbert, Lynda M. Stuart
Journal: Immunity (2011)
Forearm beta adrenergic receptor-mediated vasodilation is impaired, without alteration of forearm norepinephrine spillover, in borderline hypertension.
Authors: C M Stein, R Nelson, R Deegan, H He, M Wood, A J Wood
Journal: Journal of Clinical Investigation (1995)

Impaired beta adrenoceptor-mediated vasodilation associated with enhanced sympathetic activity has been reported in established hypertension. We examined whether altered beta adrenoceptor-mediated vasodilation occurs early in the disease process, when structural vascular changes are likely to be less marked, by measurement of forearm blood flow by strain gauge plethysmography after the intraarterial administration of increasing doses of a beta receptor agonist, isoproterenol, in eight subjects with borderline hypertension (BHT) and 13 normotensive (NT) controls. To determine the role of sympathetic activation in the regulation of responsiveness, we measured local sympathetic activity in the forearm by a radioisotope dilution technique. Vasodilation in response to isoproterenol, measured either as changes in forearm blood flow or forearm vascular resistance, was impaired in the BHT group so that flow at the highest dose of isoproterenol (400 ng/min) increased less (15.2 +/- 1.5 ml/100 ml per min) than in the NT group (24.4 +/- 2.4 ml/100 ml per minute) (P < 0.001). Although, systemic norepinephrine spillover was significantly greater in BHT, the difference in blood flow response to isoproterenol was not accounted for by increased local sympathetic activity since forearm norepinephrine spillover at baseline (BHT 1.0 +/- 0.4 ng/min vs. NT 0.64 +/- 0.13 ng/min) and after the administration of isoproterenol 60 ng/min (BHT 5.2 +/- 1.4 ng/min vs. NT 6.0 +/- 1.5 ng/min) and 400 ng/min (BHT 13.5 +/- 2.9 ng/min vs. NT 16.5 +/- 2.7 ng/min) did not differ between the two groups. We therefore conclude that vasodilation in response to isoproterenol is impaired in subjects with BHT and that this impairment is not explained by locally increased basal, or stimulated, sympathetic activity.
Selective effects of pentobarbital on automaticity and conduction in the intact canine heart
Authors: F. URTHALER, B. L. KRAMES, T. N. JAMES
Journal: Cardiovascular Research (1974)

The effects of sodium pentobarbital on automaticity and conduction were studied in dogs anaesthetized with three different agents. Pentobarbital was administered selectively through the nutrient arteries of the sinus node and AV junction. Interplay with directly administered and neurally released autonomic neurotransmitters was assessed. The electrophysiological effects were exclusively negative, impairing both impulse formation and conduction, independent of the anaesthetic chosen.
Bacterial lipopolysaccharide primes human neutrophils for enhanced release of arachidonic acid and causes phosphorylation of an 85-kD cytosolic phospholipase A2.
Authors: M E Doerfler, J Weiss, J D Clark, P Elsbach
Journal: Journal of Clinical Investigation (1994)

Production of leukotriene B4 (LTB4) by human neutrophils (PMN) in response to different stimuli is increased after pretreatment with lipopolysaccharides (LPS). We have analyzed the steps in arachidonic acid (AA) metabolism affected by LPS by examining release of AA and its metabolites from [3H]AA prelabeled PMN. Pretreatment of PMN for 60 min with up to 1 microgram/ml of LPS alone had no effect, but release of [3H]AA was stimulated up to fivefold during subsequent stimulation with a second agent. In the absence of LPS-binding protein (LBP), priming was maximal after pretreatment of PMN with 10 ng of LPS/ml for 60 min; in the presence of LBP maximal priming occurred within 45 min at 0.1 ng of LPS/ml and within 15 min at 100 ng of LPS/ml. Treatment of PMN with 10 ng of LPS/ml also increased uptake of opsonized zymosan by up to 60%. Phospholipids are the source of released [3H]AA. No release was observed from [14C]oleic acid (OA)-labeled PMN suggesting that phospholipolysis may be specific for [3H]AA-labeled phospholipid pools. Cytosol from PMN primed with LPS contains two to three times the phospholipase A2 (PLA2) activity of control PMN, against 1-palmitoyl-[2-14C]arachidonoyl-phosphatidylcholine. This activity is Ca2+ dependent and dithiothreitol resistant. LPS priming is accompanied by reduced migration during SDS-PAGE of an 85-kD protein, identified as a cytosolic PLA2. The extent and kinetics of this effect of LPS on cPLA2 parallel the priming of [3H]AA release, both depending on LPS concentration either with or without LBP. These findings suggest that priming by LPS of AA metabolism by PMN includes phosphorylation of an AA-phospholipid-selective cytosolic PLA2 that is dissociated from activation until a second stimulus is applied.
Phosphatidylinositol 3 kinase contributes to the transformation of hematopoietic cells by the D816V c-Kit mutant
Authors: RuJu Chian, Sonia Young, Alla Danilkovitch-Miagkova, Lars Rönnstrand, Edward Leonard, Petranel Ferrao, Leonie Ashman, Diana Linnekin
Journal: Blood (2001)
SEROLOGICAL STUDIES IN RHEUMATIC FEVER. II. SERUM COMPLEMENT IN THE RHEUMATIC STATE 1
Authors: Edward E. Fischel, Ruth H. Pauli, Jack Lesh
Journal: Journal of Clinical Investigation (1949)

In the study of rheumatic fever there has been disagreement and confusion as to the level of serum complement (C').Veil and Buccholz (1), Coburn (2), Rachmilewitz and Silberstein (3), and others have reported a low complement con- tent of the serum, which rises to normal with the subsidence of activity.This has been cited as possible evidence of the occurrence of an antigenantibody reaction in rheumatic fever, perhaps re- lated to a preceding hemolytic streptococcus in- fection.Predominantly normal or slightly low levels of C' in rheumatic fever were reported by Kellett and Thomson (4), and more recently by deGara and Goldberg (5).On the other hand, high values during the early period of rheumatic activity and low values later were noted by Hadjopoulos and Burbank (6).In this respect, rheu- matic fever did not differ from several other febrile illnesses which they studied.The variety of re- sults obtained by different investigators may be attributed in part to the variety of technics em- ployed, and the lack of a reproducible quantitative method.The purpose of the present study was to reevaluate complement levels in rheumatic fever with the accurate quantitative method developed by Mayer, Osler, Bier and Heidelberger (7, 8), in which the 50 per cent hemolytic unit is determined spectrophotometrically in the presence of ade- quate concentrations of Mg++ and Ca++.METHOD Details of the analytical procedure as outlined by Mayer et al. (8,9) were carefully observed since this is essential to obtain accurate and consistent results.
Behavioral methods for measuring effects of drugs on learning and memory in animals
Authors: George A. Heise
Journal: Medicinal Research Reviews (1984)

This review describes methods for measuring effects of drugs on learning and memory in animals, proceeding from relatively simple nonassociative learning (habituation) to classical and instrumental conditioning, and concluding with complex measures for measuring learning and memory repeatedly in the individual animal. Procedures for separating drug effects specific to learning and memory from non-specific effects on activity, motivation, sensory and motor capacity, etc., were emphasized. For each method, selected experimental examples were presented which described the action of drugs on learning and memory, elucidated the behavioral processes involved in the drug effects, or illustrated methodological points. The various procedures used to measure drug effects on learning and memory in animals have yielded a bewildering array of often-contradictory results. Quantitative differences in effectiveness of drugs in the different procedures are common. Drugs (for example, the nootropics) that alter learning or memory in a few procedures may be totally without activity in many others. How are these discrepancies to be interpreted? The apparent inconsistencies in the data can, for the most part, be understood in terms of the nature of learning and memory. "Learning" and "memory" are hypothetical processes presumed to underlie enduring changes in behavior resulting from the organism's interaction with environmental stimuli. Given such a broad definition, the prevalence of inconsistencies in the data is hardly surprising. It is unlikely that the same mechanisms should underlie all of the wide variety of behavioral changes included under the rubrics "learning" or "memory." (For a contrary view, based on consistencies among results obtained in the diverse procedures, see Zornetzer). How, then, should drug effects on learning and memory be identified or measured? The first step, of course, is to rule out those drug effects that do not conform to the definition of learning or memory. This review has described strategies and procedures by which this can be accomplished. However, even when this is done there is no single procedure that can detect drug effects on learning and memory in general, nor, in view of the heterogeneous behaviors involved, is it likely that such a universal procedure will ever be found. Thus, a multi-faceted strategy will be required. Some of the simpler procedures described in this review may be adequate for the initial identification of interesting effects.(ABSTRACT TRUNCATED AT 400 WORDS)
Acetaldehyde-modified and 4-hydroxynonenal-modified proteins in the livers of rats with alcoholic liver disease
Authors: C Li, A A Nanji, A N Siakotos, R C Lin
Journal: Hepatology (1997)

Liver proteins form adducts with acetaldehyde and are modified by products of lipid peroxidation in alcohol-fed animals. It has been hypothesized that the formation of these modified liver proteins may contribute to liver injury in alcoholic liver disease. The present work was performed to determine the extent of protein modification in rats with experimental alcoholic liver disease. Rats were fed ethanol intragastrically with medium chain triglycerides (MCTs), palm oil, corn oil, or fish oil. The group fed MCTs and ethanol showed no liver injury, rats fed palm oil and ethanol showed only fatty liver, rats fed corn oil and ethanol showed fatty liver with moderate necrosis and inflammation, and rats fed fish oil and ethanol showed fatty liver with severe necrosis and inflammation. Antibodies were raised by using keyhole limpet hemocyanin modified in vitro by 4-hydroxynonenal (4-HNE) or acetaldehyde as immunogens. When liver extracts were examined by Western blot analysis, the intensities of the acetaldehyde-modified protein band (37 kd) in the alcohol-fed animals were significantly different among the ethanol-treated groups and correlated with plasma acetaldehyde concentrations. It was strongest in rats fed fish oil and ethanol, followed by rats fed palm oil and ethanol and rats fed corn oil and ethanol, whereas rats fed MCTs and ethanol showed the weakest intensity. The 37-kd protein-adetaldehyde adduct was located mainly in the pericentral region of the liver. No acetaldehyde adduct was detected in the control rats that were pair-fed with isocaloric amounts of dextrose. Western blot analysis using the anti-4-HNE antibody showed four distinctive bands (48, 45, 40, and 38 kd) in the liver extracts of alcohol-fed rats. Control animals showed only a weak 38-kd band. Although the intensities of the 48-, 40-, and 38-kd bands were similar among the different ethanol-treated groups, the intensity of the 45-kd band decreased from MCTs and ethanol > palm oil and ethanol > or = corn oil and ethanol > fish oil and ethanol. The data indicate that the degree of liver protein modification by acetaldehyde correlates well with the severity of liver injury in ethanol-fed rats, whereas modification by the lipid peroxidation product 4-HNE shows no correlation with the severity of liver injury.
Drug Interactions in Patients on Long-term Oral Anticoagulant and Antihypertensive Adrenergic Neuron-blocking Drugs
Authors: K. J. Starr, J. C. Petrie
Journal: BMJ (1972)

The occurrence of drug interactions was studied in outpatients on anticoagulant or adrenergic neuron-blocking drugs. In the anticoagulant group (254 patients) a theoretical potential drug interaction with warfarin was noted in 33% of patients with drugs supplied by prescription and in 30% of patients with drugs taken as self-medication, though a probable adverse drug interaction was documented in only 9% of patients. The deficiency in the transfer of information about current drug therapy and the lack of awareness of patients about the hazards of anticoagulant therapy was clear.In the 64 patients on the adrenergic neuron-blocking drugs guanethidine, bethanidine, or debrisoquine a theoretical potential drug interaction was noted in 34%, but a probable adverse drug interaction was documented in only three patients. Further studies are required of other well-recognized groups of patients on drugs which are known to interact to assess the relevance and clinical importance of the formidable lists of interactions which are now available to doctors who prescribe drugs.
Delay In The Introduction Of Allergenic Foods Is Not Associated With An Increased Risk For Sensitization In A High Risk Cohort
Authors: T.J. Pitt, W. Watson, A. Ferguson, H. Dimich-Ward, A. Dybuncio, A.L. Kozyrskyj, M. Chan-Yeung, A.B. Becker
Journal: Journal of Allergy and Clinical Immunology (2010)
Decreased Lymphangiogenesis and Lymph Node Metastasis by mTOR Inhibition in Head and Neck Cancer
Authors: Vyomesh Patel, Christina A. Marsh, Robert T. Dorsam, Constantinos M. Mikelis, Andrius Masedunskas, Panomwat Amornphimoltham, Cherie Ann Nathan, Bhuvanesh Singh, Roberto Weigert, Alfredo A. Molinolo, J. Silvio Gutkind
Journal: Cancer Research (2011)

Despite our improved understanding of cancer, the 5-year survival rate for head and neck squamous cell carcinomas (HNSCC) patients remains relatively unchanged at 50% for the past three decades. HNSCCs often metastasize to locoregional lymph nodes, and lymph node involvement represents one of the most important prognostic factors of poor clinical outcome. Among the multiple dysregulated molecular mechanism in HNSCCs, emerging basic, preclinical, and clinical findings support the importance of the mTOR signaling route in HNSCC progression. Indeed, we observed here that the activation of mTOR is a widespread event in clinical specimens of HNSCCs invading locoregional lymph nodes. We developed an orthotopic model of HNSCC consisting of the implantation of HNSCC cells into the tongues of immunocompromised mice. These orthotopic tumors spontaneously metastasize to the cervical lymph nodes, where the presence of HNSCC cells can be revealed by histologic and immunohistochemical evaluation. Both primary and metastatic experimental HNSCC lesions exhibited elevated mTOR activity. The ability to monitor and quantitate lymph node invasion in this model system enabled us to explore whether the blockade of mTOR could impact HNSCC metastasis. We found that inhibition of mTOR with rapamycin and the rapalog RAD001 diminished lymphangiogenesis in the primary tumors and prevented the dissemination of HNSCC cancer cells to the cervical lymph nodes, thereby prolonging animal survival. These findings may provide a rationale for the future clinical evaluation of mTOR inhibitors, including rapamycin and its analogues, as part of a molecular-targeted metastasis preventive strategy for the treatment of patients with HNSCC.
Letter: Price of prostatectomy.
Authors: A Elton, B M Wright
Journal: BMJ (1974)

tical solution.Mr. Illich foresees a cata- clylmic collapse of our present institutionalized values and Dr. Bradshaw envisages a similar end.One would like to think that this particular era of La condition humaine will end "not with a bang but with a sigh."There may be many small but vital pockets of hope and resistance standing out in the Western world.Let us hope that some of these have among their numtber "men of medicine."-Iam, etc.,
The National Health Service Corps in the 1990s
Authors: Ciro V. Sumaya
Journal: JAMA (1995)

To the Editor.  —As founder and director of the Area Health Education Center in South Texas, I was familiar with the fine work of the National Health Service Corps (NHSC) long before I was appointed administrator of its parent agency, the Health Resources and Services Administration, earlier this year.  I was surprised, therefore, to read the article by Dr Pathman and colleagues 1 describing results of a study of NHSC scholars who served their obligations in rural areas in the late 1980s—a time when the NHSC was scheduled to be phased out of existence and hardly a period when optimal conditions could be expected or maximal support extended to those in the field.  While thoughtful commentary on the NHSC is always welcome, the cohort studied by Pathman et al had experiences dramatically different from those of today's NHSC clinicians. The National Health Service Corps Revitalization Amendments of 1990 provided increased
Ornithine Transcarbamylase Deficiency — A Cause of Bizarre Behavior in a Man
Authors: Eugene P. DiMagno, John E. Lowe, Philip J. Snodgrass, James D. Jones
Journal: New England Journal of Medicine (1986)

THE most commonly reported deficiency of the urea-cycle enzymes is that of ornithine transcarbamylase (E.C.2.1.3.3).1 It is inherited as an X-linked defect.2 , 3 In the usual forms of this disease, ornithine transcarbamylase activity in the liver varies widely in heterozygous females but is usually undetectable in males. Consequently, the disease occurs later in females and its clinical manifestations are less severe, whereas affected males usually die before they are one year old. However, a few boys have been described who had 5 to 30 percent of normal enzyme activity and later onset of symptoms.1 , 4 We report the case of an unusual, . . .