tbuckley/cabot-search huggingface dataset:
Glucose action `beyond ionic events' in the pancreatic β cell
Authors: Toru Aizawa, Mitsuhisa Komatsu, Nahoko Asanuma, Yoshihiko Sato, Geoffrey W.G Sharp
Journal: Trends in Pharmacological Sciences (1998)

For normal glucose homeostasis, insulin release by the pancreatic beta cell is vital. Until recently, it was thought that glucose-induced ionic events, such as closure of the ATP-sensitive K+ (KATP) channels, membrane depolarization, activation of the L-type voltage-dependent Ca2+ channels, Ca2+ influx and elevation of cytosolic free Ca2+, constitute the main signalling pathway in beta-cell stimulus-secretion coupling. However, since the discovery of 'non-ionic' glucose actions in the beta cell by the Aizawa and Henquin laboratories in 1991, data have accumulated that strongly indicate the physiological relevance of this signalling pathway. In this review, Toru Aizawa and colleagues discuss how the KATP channel-Ca2+ hypothesis was formulated, what was overlooked in the hypothesis, and then provide a comprehensive view of stimulus-secretion coupling in the beta cell, with an emphasis on non-ionic glucose actions.
Evaluation of antiarrhythmic drugs on defibrillation energy requirements in dogs. Sodium channel block and action potential prolongation.
Authors: D S Echt, J N Black, J T Barbey, D R Coxe, E Cato
Journal: Circulation (1989)

Antiarrhythmic drugs have been reported to produce variable effects on defibrillation energy requirements. However, the relation between the in vitro electrophysiologic effects of these agents and the changes in defibrillation energy requirements have not been systematically examined. Therefore, we evaluated the effects of the sodium channel blocking drugs lidocaine and procainamide, the action potential prolonging drugs N-acetyl procainamide and clofilium, and the potassium current blocker cesium in acute canine models with the same internal spring and epicardial patch electrodes used in humans for ventricular defibrillation testing. Ten series of experiments were performed in 78 dogs. Nonlinear regression was used to derive curves of energy dose versus percent successful defibrillation attempts and the 50% and 90% effective energy dose for each experimental condition. Saline control experiments indicated that the preparation was stable throughout the 6-hour duration of the experiments. Lidocaine doubled the defibrillation energy requirement (p less than 0.001) at a mean plasma concentration of 8.2 micrograms/ml. The effect of lidocaine on defibrillation energy was reversible, present at therapeutic plasma concentrations, linearly related to plasma concentration (r = 0.69, p less than 0.002), and present even after only 5-second episodes of ventricular fibrillation. In contrast, procainamide had no effect on defibrillation energy at mean plasma concentrations of 8.5 and 13 micrograms/ml, even after prolonged (30-second) episodes of ventricular fibrillation, whereas N-acetyl procainamide, clofilium, and cesium all decreased the energy requirement for defibrillation by 13-27%. Moreover, with the addition of N-acetyl procainamide, there was a trend toward diminishing the increase in defibrillation energy requirement caused by lidocaine. All agents prolonged the mean ventricular fibrillation cycle length. Lidocaine shortened the QT interval, whereas all other agents increased the QT (p less than 0.05). The major electrophysiologic effect of lidocaine is of sodium channel blockade, whereas, N-acetyl procainamide, clofilium, and cesium predominantly increase the action potential duration, and procainamide exerts both effects. Thus, these data indicate that sodium channel block and action potential prolongation exert significant and antagonistic modulating effects on defibrillation energy requirements.
Autopsy Studies in Atherosclerosis
Authors: JAMES C. ROBERTS, ROBERT H. WILKINS, CAMPBELL MOSES
Journal: Circulation (1959)

The distribution and severity of gross atherosclerosis at autopsy in 153 patients dying with morphologic evidence of atherosclerotic catastrophe in the heart, aorta, or brain were compared with that in 347 "noncatastrophic" patients. This study used a grading system for atherosclerosis that included consideration of both the extent and severity of intimal involvement. The study groups contained 78 males and 28 females with catastrophes in the heart, 26 males and 10 females with catastrophes in the aorta, and 20 males and 20 females with catastrophes in the brain. A significantly larger proportion of men had vascular catastrophes than did women. However, there was no sex difference demonstrated in the distribution and severity of atherosclerosis.
The effect of octreotide on breathing and the ventilatory response to CO2 in conscious dogs
Authors: K Cao, RR Grunstein, KY Ho, CE Sullivan
Journal: European Respiratory Journal (1998)

It has been reported that injection of somatostatin into the brain-stem will lead to apnoea in animals. The aim of this study was to determine whether peripheral administration of octreotide, an analogue of somatostatin, could influence the control of breathing. We measured the tidal volume, respiratory rate and ventilatory response to CO2, before and after the intravenous injection of two dose levels of octreotide (0.1 mg and 0.5 mg) or saline in four conscious adult dogs. Injection of octreotide altered the breathing pattern with a mean decrease in the respiratory frequency of 23% (p&lt;0.05) and an increase in the tidal volume by 16% (p&lt;0.05), resulting in no net change in ventilation. The normal value of the ventilatory response to CO2 ranged between 1.0-3.2 L x min(-1) x mmHg(-1), with a minor variance within each dog but a significant difference amongst the four dogs (p&lt;0.05). No significant change in the ventilatory response to CO2 was observed after octreotide. We conclude that intravenous octreotide alters the pattern of breathing but preserves minute ventilation; peripheral administration of octreotide does not influence the ventilatory response to CO2.
Christopher John Goodwill
Authors: C. Patey
Journal: BMJ (2011)

Christopher John Goodwill came from a medical family, including his mother, who qualified from King’s College Hospital in 1926 and from whom he learnt much medicine.

After house jobs in London, he was in the army for his national service, mostly as a medical officer with the Grenadier Guards. Returning to civilian life in 1960, when most national service was ending, he worked at the Brook Hospital, Woolwich—excellent training for the MRCP. Following this, he worked at the Brompton Hospital, being particularly interested in the treatment of …
Implications of the Multicenter Automatic Defibrillator Implantation Trial-II
Authors: Fahim H. Jafary
Journal: Annals of Internal Medicine (2006)

Letters3 January 2006Implications of the Multicenter Automatic Defibrillator Implantation Trial-IIFahim H. Jafary, MDFahim H. Jafary, MDFrom the Aga Khan University Hospital, Karachi, Pakistan.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-144-1-200601030-00016 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:Al-Khatib and colleagues (1) failed to emphasize a major limitation of their study: lack of applicability to persons living in developing countries—over one third of the world's population. Implantable defibrillators are too prohibitively expensive for these nations to even consider. Given that the major contribution to the global burden of cardiovascular disease is anticipated to arise from developing nations (2), it is an unfortunate reality that many deaths that could be prevented by ICDs will occur in these countries.There is an urgent need for cheaper (even if significantly less sophisticated) devices to be marketed to developing ...References1. Al-Khatib SM, Anstrom KJ, Eisenstein EL, Peterson ED, Jollis JG, Mark DB, et al. Clinical and economic implications of the Multicenter Automatic Defibrillator Implantation Trial-II. Ann Intern Med. 2005;142:593-600. [PMID: 15838065] LinkGoogle Scholar2. Yusuf S, Vaz M, Pais P. Tackling the challenge of cardiovascular disease burden in developing countries [Editorial]. Am Heart J. 2004;148:1-4. [PMID: 15215784] CrossrefMedlineGoogle Scholar Author, Article, and Disclosure InformationAuthors: Fahim H. Jafary, MDAffiliations: From the Aga Khan University Hospital, Karachi, Pakistan.Disclosures: None disclosed. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoClinical and Economic Implications of the Multicenter Automatic Defibrillator Implantation Trial-II Sana M. Al-Khatib , Kevin J. Anstrom , Eric L. Eisenstein , Eric D. Peterson , James G. Jollis , Daniel B. Mark , Yun Li , Christopher M. O'Connor , Linda K. Shaw , and Robert M. Califf Implications of the Multicenter Automatic Defibrillator Implantation Trial-II Sana M. Al-Khatib , Daniel B. Mark , and Robert M. Califf Implications of the Multicenter Automatic Defibrillator Implantation Trial-II William S. Weintraub Metrics 3 January 2006Volume 144, Issue 1Page: 65KeywordsCardiovascular diseasesConflicts of interestImplantable defibrillators ePublished: 3 January 2006 Issue Published: 3 January 2006 Copyright & PermissionsCopyright © 2006 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
The Stomach and Anaemia
Authors: Paul G. Hattersley
Journal: JAMA (1967)

Monographs on highly specialized subjects often make rather dry reading unless the author writes with style, as well as with interest and authority. With his 27 years experience at Oxford and a personal bibliography which includes scores of pertinent titles, Dr. Witts writes about the stomach and anemia with obvious interest and authority. The result is a highly valuable compendium of facts. Stylish writing is not his forte, however, and the text plods just a bit.  The author seriously questions the validity of the concept of achlorhydria as traditionally determined by a single body dose of histamine, and he emphasizes the superiority of the augmented histamine test. He very thoroughly describes pernicious anemia, its pathogenesis, diagnosis, and natural history. Quite properly, he emphasizes the importance of recognizing pre-anemic cases, and points out that carcinoma of the stomach occurs much more commonly in persons with pernicious anemia than in others of
The PI3K Pathway As Drug Target in Human Cancer
Authors: Kevin D. Courtney, Ryan B. Corcoran, Jeffrey A. Engelman
Journal: Journal of Clinical Oncology (2010)

The phosphatidylinositol 3-kinase (PI3K) signaling axis impacts on cancer cell growth, survival, motility, and metabolism. This pathway is activated by several different mechanisms in cancers, including somatic mutation and amplification of genes encoding key components. In addition, PI3K signaling may serve integral functions for noncancerous cells in the tumor microenvironment. Consequently, therapeutics targeting the PI3K pathway are being developed at a rapid pace, and preclinical and early clinical studies are beginning to suggest specific strategies to effectively use them. However, the central role of PI3K signaling in a large array of diverse biologic processes raises concerns about its use in therapeutics and increases the need to develop sophisticated strategies for its use. In this review, we will discuss how PI3K signaling affects the growth and survival of tumor cells. From this vantage, we will consider how inhibitors of the PI3K signaling cascade, either alone or in combination with other therapeutics, can most effectively be used for the treatment of cancer.
TI-201 Positive, Ga-67 Negative Hepatoblastoma: A Case Report of a 12-Year-Old Boy
Authors: ELIZABETH J. BERNARD, WAYNE NICHOLLS, ROBERT HOWMAN-GILES, ALEX KAN, MICHAEL STEVENS
Journal: Clinical Nuclear Medicine (1997)

Hepatoblastoma is a primary liver neoplasm in which prompt diagnosis and resection are critical to long-term survival. Nuclear scintigraphy plays an important role in the characterization of hepatic masses. The authors present an unusual case of hepatoblastoma in a 12-year-old boy in whom Ga-67 scintigraphy and serum alpha-fetoprotein were negative. Positive TI-201 scintigraphy pointed toward the true malignant nature of the mass and should be considered in the investigation of hepatic masses in childhood.
Payment incentives for GPs bear no relation to health benefits
Authors: Roger Dobson
Journal: BMJ (2006)

Incentive payments in the new NHS contract for primary care bear no relation to likely health benefits for their patients, concludes new research.

In some cases GPs will get paid more for treatments that save fewer lives than they will for treatments that achieve better results, say the authors of a study in the Journal of Health Services Research & Policy (2006:11:27-31).

Angiotensin converting enzyme (ACE) inhibitors for heart failure will save a maximum of 308 lives per 100 000 people in the population and attract a maximum practice payment of £2400 ($4240; €3510). Yet …
Hepatic vascular disease and portal hypertension in polycythemia vera and agnogenic myeloid metaplasia: A clinicopathological study of 145 patients examined at autopsy
Authors: Ian R. Wanless, Powers Peterson, Asha Das, John K. Boitnott, G. William Moore, Vincent Bernier
Journal: Hepatology (1990)

The pathogenesis of portal hypertension arising in patients with myeloproliferative disorders has been difficult to understand because liver biopsy findings often show minimal changes. It has been suggested that increased splenic blood flow, hepatic infiltration with hematopoietic cells or sinusoidal fibrosis may be important. We have reviewed the autopsy findings and clinical histories of 97 patients with polycythemia vera and 48 patients with agnogenic myeloid metaplasia collected from three institutions and from the Polycythemia Vera Study Group. Cirrhosis was present in seven patients, one of whom had bleeding varices. Esophageal varices were present clinically in 10 patients without cirrhosis (seven polycythemia and three agnogenic myeloid metaplasia). All of these patients had lesions in small or medium-sized portal veins and four had stenosis of the extrahepatic portal vein with histology compatible with organized thrombi. Nodular regenerative hyperplasia occurred in 14.6% and correlated closely with the presence of portal vein lesions. Thirty patients had > 500 ml of ascites, seven of these patients also had varices and six of them had hepatic vein thrombosis. Ascites also correlated with hepatic vein disease confined to small intrahepatic branches. No correlation was seen between hepatic hematopoietic infiltration and signs of portal hypertension. We conclude that esophageal varices are common and are almost always associated with portal vein lesions visible by light microscopy. These portal vein lesions, and the secondary effects of nodular regenerative hyperplasia and portal hypertension, are most likely a result of portal vein thrombosis in patients with myeloproliferative disorders. (HEPATOLOGY 1990;12:1166–1174).
IMPACT OF COMBINED USE OF OPTICAL COHERENCE TOMOGRAPHY AND VIRTUAL HISTOLOGY INTRAVASCULAR ULTRASOUND IN ASSESSMENT OF STABLE AND UNSTABLE CORONARY PLAQUES
Authors: Shohei Yoshida, Kenji Miwa, Kenshi Hayashi, Masa-aki Kawashiri, Honin Kanaya, Masakazu Yamagishi
Journal: Journal of the American College of Cardiology (2012)
Gonococcal pilus vaccine. Studies of antigenicity and inhibition of attachment.
Authors: E C Tramont, J C Sadoff, J W Boslego, J Ciak, D McChesney, C C Brinton, S Wood, E Takafuji
Journal: Journal of Clinical Investigation (1981)

A gonococcal pilus vaccine or placebo was injected subcutaneously or intramuscularly into 71 human volunteers. The vaccine was found to be safe. The principal adverse reaction was a complaint of a sore arm, which was caused, at least in part, to the volume of material injected. 6 of 64 (9%) volunteers receiving the larger doses also complained of malaise. The vaccine was found to be antigenic. All of the volunteers developed an immunoglobulin class-specific antibody response as measured by a solid phase radioimmunoassay. The antibody was capable of blocking the attachment of gonococci to epithelial cells. A slight antibody response was also demonstrated to gonococcal lipopolysaccharide but the antibody responsible for blocking attachment of gonococci was directed entirely at the pilus protein. The stimulated antibodies were shown to crossreact with isolated pili of heterologous gonococcal strains and to block the attachment of heterologous gonococci. Absorption of immune sera by a heterologous pilus reduced the inhibition of attachment antibodies to pre-immune level, suggesting that the immune response was directed at a common pilus determinant.
High-Altitude Pulmonary Edema
Authors: Robert Blair Schoene, Peter H. Hackett, William R. Henderson, E. Helene Sage, Marguerite Chow, Robert C. Roach, William J. Mills, Thomas R. Martin
Journal: JAMA (1986)

To evaluate the cellular and biochemical composition of bronchoalveolar fluid in high-altitude pulmonary edema (HAPE), we performed bronchoalveolar lavage in three climbers with HAPE in a research facility at 4400 m on Mount McKinley. Three healthy climbers were used as controls. The HAPE fluids contained marked increases in high-molecular-weight proteins, erythrocytes, and leukocytes, most of which were alveolar macrophages. The HAPE fluids also contained detectable amounts of leukotriene B4 and other lipoxygenase products of arachidonic acid metabolism, complement fragments (C5a), inhibitors of neutrophil chemotaxis, and acid proteases but not hydroxyproline, a constituent of collagen. The data from this study indicate that HAPE involves a transient "large pore" leak in the pulmonary circulation. Despite the presence of two potent mediators of inflammation, leukotriene B<sub>4</sub>and C5a, HAPE is not characterized by the intense neutrophil accumulation that is typical of other forms of acute lung injury. (<i>JAMA</i>1986;256:63-69)
Crohn's disease adherent-invasive <i>Escherichia coli</i> colonize and induce strong gut inflammation in transgenic mice expressing human CEACAM
Authors: Frédéric A. Carvalho, Nicolas Barnich, Adeline Sivignon, Claude Darcha, Carlos H.F. Chan, Clifford P. Stanners, Arlette Darfeuille-Michaud
Journal: The Journal of Experimental Medicine (2009)

Abnormal expression of CEACAM6 is observed at the apical surface of the ileal epithelium in Crohn's disease (CD) patients, and CD ileal lesions are colonized by pathogenic adherent-invasive Escherichia coli (AIEC). We investigated the ability of AIEC reference strain LF82 to colonize the intestinal mucosa and to induce inflammation in CEABAC10 transgenic mice expressing human CEACAMs. AIEC LF82 virulent bacteria, but not nonpathogenic E. coli K-12, were able to persist in the gut of CEABAC10 transgenic mice and to induce severe colitis with reduced survival rate, marked weight loss, increased rectal bleeding, presence of erosive lesions, mucosal inflammation, and increased proinflammatory cytokine expression. The colitis depended on type 1 pili expression by AIEC bacteria and on intestinal CEACAM expression because no sign of colitis was observed in transgenic mice infected with type 1 pili-negative LF82-Delta fimH isogenic mutant or in wild-type mice infected with AIEC LF82 bacteria. These findings strongly support the hypothesis that in CD patients having an abnormal intestinal expression of CEACAM6, AIEC bacteria via type 1 pili expression can colonize the intestinal mucosa and induce gut inflammation. Thus, targeting AIEC adhesion to gut mucosa represents a new strategy for clinicians to prevent and/or to treat ileal CD.
Effect of Gorse Extracts on Uterus
Authors: W. Smith, A. Wilson
Journal: BMJ (1943)

BIUTISH ~~~~~~~~~~~MEDICAL JOURNAL pericardial sac.At necropsy fatal cases constantly show cardiac dilatation and pulmonary oedema and -congestion.The pulmonary oedema is evidence of left-sided heart failure.Treatment should comp*e prompt cessation of transfusion, the administration of oxygen, and the injection of morphine and atropine.Adrenaline is contraindicated.Venesection may be necessary to relieve the load on the right heart.A reasonable rate of transfusion in severe chronic anaemias is 40 drops a minute, and the giving of one pint of whole blood should be spread over at least three hours if disasters from circulatory overloading are to be avoided.I desire to express my thanks to
Facial structure in the sudden infant death syndrome: case-control study
Authors: K. Rees, A. Wright, J. W Keeling, N. J Douglas
Journal: BMJ (1998)

The cause of the sudden infant death syndrome is unclear. Polygraphic recordings of 30 infants who subsequently died of the syndrome showed a significant increase in mixed and obstructive apnoeas compared with well matched controls.1 Postmortem examination suggests upper airway narrowing in victims of the syndrome. The decreased number of cases of sudden infant death syndrome after advice to put infants to sleep supine suggests a posture dependent cause, and recent evidence suggests that upper airways of sleeping infants are more widely patent supine than prone.2 Thus sleeping supine might decrease obstructive apnoeas.

An increased frequency of sudden infant death syndrome and apparent life threatening events in infants has been found in the families of patients with the obstructive sleep apnoea/hypopnoea syndrome. 3 4 We found that retroposition of the maxilla was a common feature in families who had both the obstructive sleep apnoea/hypopnoea and sudden infant death syndromes.3 …
Protein-Lipid Relationships in Experimental Canine Atherosclerosis
Authors: DAVID P. BARR, ELLA M. RUSS, HOWARD A. EDER, FORREST E. KENDALL, LIESE L. ABELL
Journal: Circulation Research (1955)

The applicability of Cohn's method number 10 to the study of dog plasma has made possible this investigation of experimental canine atherosclerosis. Administration of thiouracil which causes hypercholesterolemia but no atherosclerosis in dogs produces no considerable alteration in the distribution of plasma lipoproteins. High cholesterol feeding and administration of thiouracil causes both atherosclerosis and significant alterations in the distribution of lipoproteins.
Neural constraints on cognition in sleep
Authors: Helene Sophrin Porte
Journal: Behavioral and Brain Sciences (2000)

Certain features of Stage NREM sleep – for example, rhythmic voltage oscillation in thalamic neurons – are physiologically inhospitable to “REM sleep processes.” In Stage 2, the sleep spindle and its refractory period must limit the incursion of “covert REM,” and thus the extent of REM-like cognition. If these hyperpolarization-dependent events also inform Stage NREM cognition, does a “1-gen” model suffice to account for REM-NREM differences? [Nielsen]
Legislation on juniors' hours,
Authors: P F Jones
Journal: BMJ (1994)

EDITOR, - In the continuing debate on the regulation of the hours worked by junior doctors1 attention should be given to the fact that junior doctors form a large and disparate group with differing requirements. Most preregistration and senior house officers in the acute specialties work for most of their time on duty. It is therefore right to provide regulated protection from undue loss of …
Constitutive androstane receptor activation stimulates faecal bile acid excretion and reverse cholesterol transport in mice
Authors: Anne Laure Sberna, Mahfoud Assem, Thomas Gautier, Jacques Grober, Boris Guiu, Aline Jeannin, Jean-Paul Pais de Barros, Anne Athias, Laurent Lagrost, David Masson
Journal: Journal of Hepatology (2010)