tbuckley/cabot-search huggingface dataset:
Enhanced vasodilatation to endothelin antagonism in patients with compensated cirrhosis and the role of nitric oxide
Authors: A Helmy, David Newby, R Jalan, Peter Hayes, David Webb
Journal: Gut (2003)

<b>Background and aims:</b> Patients with advanced cirrhosis have systemic vasodilatation and increased nitric oxide (NO) production despite activated vasopressor systems, including the endothelin system. The aims of this study were to assess the contribution of endogenous endothelin 1 (ET-1) and NO to the maintenance of basal forearm vascular tone in patients with preascitic cirrhosis (n=7) and in age and sex matched healthy controls (n=7). <b>Methods:</b> Using venous occlusion plethysmography, forearm blood flow (FBF) responses to subsystemic locally active intra-arterial infusion of BQ-123 (a selective endothelin type A receptor (ET<sub>A</sub>) receptor antagonist; 10 nmol/min) were measured before and during application of an <b>“</b>NO clamp”: a balanced co-infusion of l-<i>N</i><sup><i>G</i></sup>-monomethyl-arginine (a selective NO synthase inhibitor) and sodium nitroprusside (an exogenous NO donor) to block endogenous NO production and restore NO mediated basal FBF, respectively. <b>Results:</b>l-NMMA infusion produced a reduction in FBF (p&lt;0.001) which was similar in both groups. Before applying the <b>“</b>NO clamp”, BQ-123 caused an increase in FBF in both groups (p&lt;0.001) that was greater in patients with cirrhosis (p&lt;0.01). During the <b>“</b>NO clamp”, BQ-123 induced vasodilatation was abolished in controls and attenuated in patients (p&lt;0.001) but remained significantly greater in patients with cirrhosis (p&lt;0.01). <b>Conclusions:</b> These findings indicate a greater ET<sub>A</sub> mediated contribution of endogenous ET-1 to the maintenance of basal forearm vascular tone in patients with preascitic cirrhosis. In addition, enhanced vasodilatation to ET<sub>A</sub> receptor antagonism in cirrhosis cannot be entirely attributed to NO release but is likely to be related to reversal of direct ET-1 mediated tone.
Effect of pregnancy on relaxation of rat aorta to magnesium
Authors: C P Aloamaka, M Ezimokhai, J Morrison, T Cherian
Journal: Cardiovascular Research (1993)

Objective: There is evidence for involvement of the endothelium in magnesium induced vasodilatation. In view of the use of magnesium in the treatment of women with pre-eclampsia, and because the mechanism of the vascular effects of magnesium in pregnancy is not fully understood, this study examined the dilator response to magnesium of aortic rings from pregnant and non-pregnant rats. The role of the endothelium was also evaluated. Methods: Rings from descending thoracic aorta of pregnant and non-pregnant rats, contracted with either 10−7M phenylephrine or 40 mM potassium chloride, were relaxed with increasing concentrations of MgSO4 in the presence or absence of 10−6M indomethacin or endothelium. The rings were also contracted to 10−5 M phenylephrine, in calcium-free medium containing 0, 1.2, or 4.8 mM MgSO4. Results: The relaxation of aortic rings from pregnant rats to MgSO4 was greater when stimulated with potassium chloride but that of rings from non-pregnant rats was greater when stimulated with phenylephrine. Neither the presence of MgSO4 nor pregnancy had any effect on intracellular calcium dependent contraction. The relaxations of rings from either pregnant or non-pregnant rats to MgSO4 were not significantly altered by de-endothelialisation or pretreatment with 10−6 M indomethacin. Conclusions: The effect of pregnancy on magnesium induced relaxation of rat aortic smooth muscle was dependent on the agent used to induce contraction in the tissue, probably because pregnancy exerted different actions on receptor and voltage operated calcium channels. This effect of pregnancy was independent of either endothelial function or prostaglandin synthesis. Neither pregnancy nor the presence of magnesium affected the release of intracellular stored calcium. Cardiovascular Research 1993;27:1505-1509
Ureteric Obstruction by Clot During Anticoagulant Treatment
Authors: S. F. O. Beirn, S. Lavelle
Journal: BMJ (1964)

MICAL JOUMILNow that its field of usefulness has been defined it is proposed to combine it with surgery and radiotherapy, and to discover if its effect is greater under conditions of slowed circulation and hypothermia. SUMMARYThirty patients with inoperable cerebral tumours have been treated by intracarotid injection of ethoglucid (triethyleneglycol diglycidyl ether, " epodyl ").The marrow-depressant effects were less than in other cytotoxic drugs and there were no other important toxic symptoms.Thirteen of the 30 patients had objectively recordable remissions.This drug cannot effect complete tumour destruction, but it can arrest growth in some cases for varying times.It is more effective in the less malignant cerebral gliomas.
Effects of Aspirin on Platelet-Neutrophil Interactions
Authors: A. López-Farré, C. Caramelo, A. Esteban, M. L. Alberola, I. Millás, M. Montón, S. Casado
Journal: Circulation (1995)

Background In recent studies, the hypothesis has been raised that the mechanisms by which aspirin acts as a protective anti-ischemic agent exceed the inhibition of platelet thromboxane A 2 synthesis. Recently, new data have been obtained disclosing a platelet-antiaggregating effect by neutrophils, which occurs through a nitric oxide (NO)/cGMP-dependent pathway. Methods and Results The present study, using platelets and neutrophils from normal subjects, was undertaken to assess the putative effect of aspirin on the neutrophil-mediated, platelet-inactivating effect. Aspirin facilitated the inhibitory effect of neutrophils on platelet activation by thrombin, ADP, or epinephrine. This effect was equally evident in vitro and in blood samples of normal individuals taking aspirin. A significant stimulation of NO-mediated mechanisms in the presence of aspirin was disclosed by different methods, as follows: (1) the increased metabolism of arginine to citrulline, (2) the increase of cGMP in the platelet/neutrophil system, and (3) the inhibitory action of the l -arginine (L-Arg)–competitive analogue L-NMMA, which was reversed by L-Arg. The effect of aspirin appeared to be related to cyclooxygenase inhibition, since it was reproduced by using indomethacin. The vasoconstricting peptide endothelin-1 (ET-1) reversed the effect of aspirin through the endogenous production of platelet-activating factor (PAF) by neutrophils, as judged by the marked inhibitory effect of the PAF antagonist BN-52021. Conclusions Our results show that a significant part of the effect of aspirin on platelet activation involves a neutrophil-mediated, NO/cGMP-dependent mechanism. The presence of ET-1 counterbalances these effects of neutrophils on platelet activation, therefore acting as an indirect proactivating agent. These results add new elements for interpreting the effects of aspirin on the interactions between blood cells, with special reference to high endothelin states (for example, ischemia/reperfusion processes).
<scp>CX</scp>3<scp>CL</scp>1 in allergic diseases: not just a chemotactic molecule
Authors: V. Julia
Journal: Allergy (2012)

Abstract Allergic asthma and atopic dermatitis ( AD ) are two allergic diseases that are primarily driven by the activation of T helper ( T h)2 cells. T h2 cells produce cytokines that directly contribute to the symptoms of these diseases. The recruitment and maintenance of T h2 cells into the target tissues are two key events in the pathogenesis of allergic asthma and AD. While migration is mediated by both chemokines and lipid mediators such as leukotrienes and prostaglandins, very little is known about the molecules involved in lymphocyte survival and maintenance in inflamed tissues. However, chemokines could also play a role in this phenomenon. An example of this could be illustrated by CX 3 CL 1, also known as fractalkine. CX 3 CL 1 is a chemokine that is upregulated in some inflammatory diseases including allergic pathologies and that was recently demonstrated to provide a survival signal upon binding to its unique receptor CX 3 CR 1.
Practical and Theoretical Aspects of Psychoanalysis
Authors: Martin R. Lipp
Journal: JAMA (1975)

This posthumously published volume represents a fascinating achievement by an important figure in American psychoanalysis. The book has evolved from a 1936 version under a briefer title, through a 1950 revision, to the present edition. The final product is a very personal document portraying the personal evolution of Lawrence Kubie, as well as that segment of the psychoanalytic community that looked to him for leadership. Kubie calls himself a heretic, a person who had no "truck with any doxologies," and he deeply regretted that his earlier volumes were accused of "rigidity" by the nonorthodox. Paradoxically, the more traditional analysts regarded the same work as "heterodox." The present volume continues Kubie's attempt to inform prospective patients, their families and friends, medical advisors, and other counselors what psychoanalysis is really like. And the attempt is successful. The interested reader, physician or layman, will find an enormously articulate description of how Freudian psychoanalysis
Organization versus activation: the role of endocrine-disrupting contaminants (EDCs) during embryonic development in wildlife.
Authors: L J Guillette, D A Crain, A A Rooney, D B Pickford
Journal: Environmental Health Perspectives (1995)

Many environmental contaminants disrupt the vertebrate endocrine system. Although they may be no more sensitive to endocrine-disrupting contaminants (EDCs) than other vertebrates, reptiles are good sentinels of exposure to EDCs due to the lability in their sex determination. This is exemplified by a study of alligators at Lake Apopka, Florida, showing that EDCs have altered the balance of reproductive hormones resulting in reproductive dysfunction. Such alterations may be activationally or organizationally induced. Much research emphasizes the former, but a complete understanding of the influence of EDCs in nature can be generated only after consideration of both activational and organizational alterations. The organizational model suggests that a small quantity of an EDC, administered during a specific period of embryonic development, can permanently modify the organization of the reproductive, immune, and nervous systems. Additionally, this model helps explain evolutionary adaptations to naturally occurring estrogenic compounds, such as phytoestrogens.
A behavior-genetic approach to multiple chemical sensitivity.
Authors: D B Newlin
Journal: Environmental Health Perspectives (1997)

This report emphasizes the application of behavior-genetic designs to the study of sensitivity to toxic chemicals, and features of multiple chemical sensitivity and substance abuse that are polar opposites. The implications of these issues for future research are discussed in relation to twin, adoption, and sibling pair studies, as well as in relation to the degree to which genetically selected lines of rodents that have been developed in the alcoholism field are applicable to multiple chemical sensitivity.
Effects of energy delivery via a His bundle catheter during closed chest ablation of the atrioventricular conduction system.
Authors: J L Trantham, J J Gallagher, L D German, A Broughton, T Guarnieri, J Kasell
Journal: Journal of Clinical Investigation (1983)

In this paper we summarize our experience and report the characteristics of energy delivery in 23 patients who have undergone closed chest ablation of the normal atrioventricular (AV) conduction system for the treatment of refractory supraventricular arrhythmias. The induction of AV block was achieved by the synchronous delivery of electrical energy with a damped sinusoidal waveform utilizing a standard direct current defibrillator and a standard tripolar His bundle catheter. The procedure was well tolerated, though one patient experienced ventricular fibrillation, which was uneventfully converted with external paddles. Complete AV block was achieved in 20 of 23 patients and all were rendered arrhythmia free, though two still required antiarrhythmic drugs. A stable escape rhythm was seen in all patients with a cycle length of 1,294 +/- 243 ms. Creatine phosphokinase-MB was positive at low levels in 19 of 23 patients and cleared within 24 h. 99mTc pyrophosphate scans were faintly positive in only 2 of 22 patients. Left ventricular wall motion and ejection fractions were unchanged in 19 of 19 patients, two-dimensional echocardiography with microcavitation technique was unchanged in 12 of 12 patients, and a slight increase in pulmonary artery wedge pressure was seen in only 1 of 11 patients. Current, voltage, and their product (power) waveforms were recorded in 12 patients (12 recordings at a defibrillator setting of 200 J and 5 recordings at a defibrillator setting of 300 J) and revealed a complex voltage-current relationship due to changes occurring at the catheter electrode-tissue interface. At 200 J the peak values were 42.2 +/- 3.3 A, 2.16 +/- 0.11 kV, and 87.9 +/- 4.7 kW, while at 300 J the peak values were 58.2 +/- 2.8 A, 2.40 +/- 0.10 kV, and 134.4 +/- 6.7 kW, respectively. No instance of catheter disruption was seen, though "pitting" of the distal electrode (through which current passed) occurred in all but one catheter.
Imatinib and Chronic-Phase Leukemias
Authors: Laszlo G. Boros, Wai-Nang Paul Lee, Marta Cascante
Journal: New England Journal of Medicine (2002)

Therapeutic Hypothermia after Cardiac ArrestTo the Editor: The results of two studies reported in the Journal (Feb.21 issue) 1,2 suggest that therapeutic hypothermia has a beneficial effect on neurologic outcome in survivors of out-of-hospital cardiac arrest.The authors of the accompanying editorial 3 support the conclusions of these studies and firmly recommend the use of hypothermia for at least 12 hours after cardiac arrest.Before this complex intervention becomes accepted as standard therapy, a closer examination of these studies is warranted.The authors of both studies cite problems in study design and in the interpretation of their results, but neither they nor the authors of the editorial acknowledge a flaw in both studies that should cast considerable doubt on the results and conclusions.Factors known to be of prognostic importance after cardiac arrest are the brain-stem reflexes and motor responses immediately after resuscitation. 4,5 In this regard, neither study presents data reflecting the depth or severity of coma before randomization.Without these data, there is no reassurance that the hypothermia and normothermia groups were well matched according to the severity of the neurologic insult, thus raising the possibility of bias.Although arrest and resuscitation times correlate with the severity of the neurologic insult and with mortality, they cannot be used as proxies for the neurologic examination.Furthermore, the small number of patients in these trials precludes any assumption that randomization would compensate for the noted deficiencies.It is premature to conclude that therapeutic hypothermia is effective or that it can be recommended for use in comatose survivors of cardiac arrest.
THE BLOOD URIC ACID IN DISEASE
Authors: Edwin P. Jordan, Dorothy Gaston
Journal: Journal of Clinical Investigation (1932)

Because of the large number of patients in the University of Chicago Clinics showing high blood uric acid by the Koch I modification of the Folin and Benedict methods using the Folin-Wu blood filtrate, it was decided to try a different method. The method which has seemed to to yield most satisfactory results is that described by Folin (1) in which he makes use of unlaked blood filtrate, a cyanide solution stabilized by means of urea, and a uric acid reagent free from phenol reagent. This method has been used for all uric acid determinations in the Medical department since May 1931, and has proved relatively satisfactory as a clinical method. The cyanide solution, which is kept at low temperature, retains its chromophoric power well, and when used with the uric acid reagent has produced no turbid solutions. It was, of course, necessary to determine a new series of normal blood uric acid values by this method, and while the results are not wholly free from unexplained high values (see Table V), it is believed that this method, as compared with the one formerly used, gives more satisfactory results. For the purpose of comparison a few samples of blood were tested simultaneously for uric acid by the Koch modification formerly used (hereafter called  old method ) and by the Folin method at present used. Two samples from a control patient, drawn on different days, gave 7.2 and 9.2 mgm. per 100 cc. by the old method and 3.9 and 3.8 mgm. per 100 cc. respectively by the new method. One sample from a patient with chronic gout gave 12.3 and 5.6 mgm. per 100 cc. by the old and new methods respectively. The uric acid in the blood of a patient with infectious arthritis was 5.3 and 2.1 mgm. per 100 cc. by the old and new methods respectively. There was thus a deviation in all instances in the same direction and to about the same degree, but there also seemed to be less variation in the results given by the method at present in use. The first and most important consideration for diagnostic purposes in adopting a new method of determining the amount of uric acid in the venous blood was to find an upper limit for normal which would be reasonably satisfactory. In Table I are a number of uric acid determinations made on diseasefree controls. It will be seen that in only two, Case 6, W. C., and Case
Bad medicine: sexual health medicine
Authors: Des Spence
Journal: BMJ (2012)

The “clap clinic” has moved from a Portakabin behind the hospital bins to shiny new buildings. Today sexual health is jeans wearing, eyebrow pierced, cool medicine. This is to be celebrated, but care is still regrettably concentrated in secondary care and testing is restricted. But what is concerning about sexual health is its tyranny of terror messages: these are weapons of mass destruction of relationships.⇑

Consider HIV. In the 1980s we lived in constant fear of being crushed to death by colossal falling tombstones. HIV testing was allowed only after counselling and in distant …
Assessment of Nonuniformity of Transmural Myocardial Velocities by Color-Coded Tissue Doppler Imaging
Authors: Geneviève Derumeaux, Michel Ovize, Joseph Loufoua, Gérard Pontier, Xavier André-Fouet, Alain Cribier
Journal: Circulation (2000)

Background —Transmural myocardial contractile performance is nonuniform across the different layers of the left ventricular wall. We evaluated the accuracy of color M-mode tissue Doppler imaging (TDI) to assess the transmural distribution of myocardial velocities and to quantify the severity of dysfunction induced by acute ischemia and reperfusion in the inner and outer myocardial layers. Methods and Results —Thirteen open-chest dogs underwent 15 minutes of left anterior descending coronary artery occlusion followed by 120 minutes of reperfusion. M-mode TDI was obtained from an epicardial short-axis view. Systolic velocities were calculated within endocardium and epicardium of the anterior and posterior walls. Regional myocardial blood flow was assessed by radioactive microspheres. Segment shortening was measured by sonomicrometry in endocardium and epicardium of both the anterior and posterior walls. At baseline, endocardial velocities were higher than epicardial velocities, resulting in an inner/outer myocardial velocity gradient. Ischemia caused a significant and comparable reduction in endocardial and epicardial systolic velocities in the anterior wall with the disappearance of the velocity gradient. Systolic velocities significantly correlated with segment shortening in both endocardium and epicardium during ischemia and reperfusion. In the first minutes after reflow, endocardial velocities showed a greater improvement than epicardial velocities, and the velocity gradient resumed although to a limited extent, indicative of stunning. Conclusions —TDI is an accurate method to assess the nonuniformity of transmural velocities and may be a promising new tool for quantifying ischemia-induced regional myocardial dysfunction.
Metabolic and cardiotoxic effects of salbutamol
Authors: J R Brooks
Journal: BMJ (1977)

for the development of any neurotoxicity, and also that hyperbilirubinaemia is a contributory factor.The controversy over absorption of HCP through the skin and central nervous system toxicology should be placed in proper per- spective and, as pointed out in your leading article, "the reasonable conclusion seems to be that . . . the data on treatment and blood level in neonates are so heterogeneous that they should be taken only as a general indicator and that blood concentrations in animals are a poor guide to those in man."After almost seven years of regulatory restriction one has yet to see any major deleterious effect when HCP is used in the recommended way.
Sessile serrated lesion misdiagnosed as a hyperplastic polyp
Authors: Rajesh Keswani, A. Aadam, Guang-Yu Yang
Journal: Endoscopy (2014)

An 81-year-old woman presented for colonoscopy because of iron deficiency anemia. She had undergone colonoscopy 5 years previously during which a 2-cm prominent fold had been identified in the proximal ascending colon ([Fig. 1]). A biopsy of this lesion was interpreted as being a hyperplastic polyp ([Fig. 2]), although the polyp showed features of a serrated lesion. Because of clinical concern over a more sinister process, colonoscopy was repeated 1 year later. The endoscopic appearance of the area of concern was unchanged ([Fig. 3]); biopsies were again interpreted as being consistent with a hyperplastic polyp. Endoscopic resection was not performed.
Are peripheral microscopy centres ready for next generation molecular tuberculosis diagnostics?
Authors: Claudia M. Denkinger, Ioana Nicolau, Andrew Ramsay, Pamela Chedore, Madhukar Pai
Journal: European Respiratory Journal (2013)

To the Editor: 

Sputum smear microscopy is the primary test for tuberculosis (TB) in most high-burden countries. Direct Ziehl–Neelsen (ZN) microscopy is routinely implemented in these countries via a vast network of decentralised, peripheral microscopy centres (as opposed to centralised reference laboratories), often located within primary or community health centres. This decentralised approach increases access in primary care settings and may help reduce diagnostic delays [1]. However, microscopy has limitations and novel diagnostics are urgently needed, particularly in settings with high prevalence of drug resistance and HIV [1, 2].

While Xpert® MTB/RIF (Cepheid, Sunnyvale, CA, USA), a World Health Organization-endorsed test, is already being rolled out in many countries, it is intended for district or sub-district laboratories [3], and not peripheral microscopy centres. In contrast, at least four next-generation nucleic-acid amplification tests (NAATs) are now on the market, with the goal of point-of-care (POC) use in peripheral laboratories [4, 5].

Can these so-called “POC-NAATs” actually be implemented in peripheral microscopy centres? Is there sufficient expertise ( e.g . to extract DNA) and biosafety ( e.g . to process sputum)? Will the necessary infrastructure ( e.g . stable power supply) be present? Will environmental conditions ( e.g . high temperature) limit their use?

The introduction of novel diagnostics that aim to replace smear microscopy in peripheral laboratories is more likely to succeed if the new tests are designed with real world conditions in mind. However, there are limited data on landscape of microscopy centres in high-burden countries. We addressed this gap with a survey of 22 high-burden countries. We designed a one-page, 12-question survey. We focused on the most important requirements and considerations for the next generation of TB diagnostics. We included questions about ambient temperature and humidity conditions, safety, infrastructure, availability of equipment and …