tbuckley/cabot-search huggingface dataset:
Is the intercellular adhesion molecule-1/leukocyte function associated antigen 1 pathway of leukocyte adhesion involved in the tissue damage of alcoholic hepatitis?
Authors: P Burra, S G Hubscher, J Shaw, E Elias, D H Adams
Journal: Gut (1992)

Alcoholic hepatitis is characterised histologically by an intense inflammatory cell infiltrate made up predominantly of neutrophils but including other cell types, particularly lymphocytes. Leukocyte cytotoxicity requires cell adhesion, which is mediated via receptors on the leukocyte surface including leukocyte function associated antigen-1 (LFA-1) which binds to the ligand intercellular adhesion molecule-1 (ICAM-1) on the target cell. The distribution of ICAM-1 and LFA-1 expression in liver biopsy specimens from patients with alcoholic liver disease was examined to ascertain whether this pathway of leukocyte adhesion is involved in the tissue damage of alcoholic hepatitis. Specimens were stained for ICAM-1 and LFA-1 by a three step immunoalkaline-phosphatase method using monoclonal antibodies against ICAM-1 and LFA-1. LFA-1 staining on portal tract inflammatory cells and parenchymal inflammatory cells and ICAM-1 staining on liver components were examined. ICAM-1 expression on hepatocytes was significantly greater in alcoholic hepatitis compared with fatty liver (p less than 0.001) and normal controls (p less than 0.01). ICAM-1 expression correlated with the histological degree of hepatocellular damage (tau = 0.79; p = 0.0005) and parenchymal inflammation (tau = 0.65; p less than 0.001, and with LFA-1 expression on parenchymal leukocytes (tau = 0.63; p = 0.01). The ICAM-1/LFA-1 pathway may therefore be involved in leukocyte mediated tissue damage during alcoholic hepatitis.
Steroids in Treatment of Infectious Mononucleosis
Authors: John B. Riggsbee
Journal: JAMA (1967)

<h3>To the Editor:—</h3> I agree with Dr. Bender (<b>199</b>:99, 1967) that one who has witnessed the prompt improvement after treatment with steroids in the patient seriously ill with infectious mononucleosis cannot be skeptical of their value. Since it is the responsibility of a college health service to return its patients to their academic classes as promptly as possible without jeopardizing the welfare of the individual patient or other students, the Georgia Tech Student Health Service believes that any student with infectious mononucleosis who is sick enough to justify absence from classes will benefit from the use of steroids. We have used dexamethasone in more than 300 cases in the past nine years with prompt symptomatic relief, even in cases with severe infectious mononucleosis. The most satisfactory dosage schedule in terms of initial symptomatic response, prompt clearing of angina if present, and lack of relapse on completion of therapy has
Ventricular Fibrillation Occurring on Arousal from Sleep by Auditory Stimuli
Authors: HEIN J. J. WELLENS, AART VERMEULEN, DIRK DURRER
Journal: Circulation (1972)

A patient is described having syncopal attacks on being awakened from sleep by auditory stimuli. The electrocardiogram registered during these episodes showed Q-T-segment changes followed by ectopic ventricular activity and spontaneously ending attacks of ventricular fibrillation. Aside from the attacks, her ECG only showed abnormalities of the S-T segment with marked U waves. Hemodynamic and electrophysiologic studies showed no abnormalities. Coronary angiograms were normal. Following therapy with propranolol and diphenylhydantoin she has been free from syncopal episodes for the past 11 months. The mechanism responsible for the Q-T-segment changes and ventricular tachyarrhythmias is not understood.
792 STRUCTURAL CHARACTERISTICS OF MISFOLDED PROTEINS IN LIVER DISEASE: EVIDENCE FOR CROSS β-SHEET CONFORMATION IN MALLORY-DENK BODIES BUT NOT IN OTHER HEPATOCYTIC AGGREGATES
Authors: V.S. Mahajan, T. Klingstedt, K.P.R. Nilsson, A. Fuchsbichler, K. Kashofer, P.M. Abuja, H. Denk, K. Zatloukal
Journal: Journal of Hepatology (2010)
A Genome Wide Approach to Identify Genetic Determinants of Asthma Traits Related to Airway Function in Populations of African Descent
Authors: Y TSAI, R MATHIAS, A GRANT, N RAFAELS, T HAND, A TOGIAS, N HANSEL, G DIETTE, N ADKINSONJR, M LIU
Journal: Journal of Allergy and Clinical Immunology (2008)
Meta-analysis shows difference between antidepressants and placebo is only significant in severe depression
Authors: Susan Mayor
Journal: BMJ (2008)

New generation antidepressants achieve almost no benefit compared with placebo in mild to moderate depression, with slightly more benefit in severe depression but only because of less response to placebo, a meta-analysis of clinical trial data has shown.

Researchers analysed all available data from clinical trials submitted to the US Food and Drug Administration for the licensing of four selective serotonin or serotonin-noradrenaline reuptake inhibitors—fluoxetine (Prozac), venlafaxine (Efexor), nefazodone (Serzone), and paroxetine (Seroxat, Paxil).

They analysed the degree to which people improved in relation to the initial severity of the depression in people randomised to drug or placebo.

Results showed almost no difference between the effects of drug treatment and placebo at moderate levels of initial depression, rising to a relatively …
A systems approach to molecular structure, intermolecular recognition, and emergence‐dissolvence in medicinal research
Authors: Bernard Testa, Lemont B. Kier, Pierre‐Alain Carrupt
Journal: Medicinal Research Reviews (1997)

Keywords:

molecular structure;
molecular properties;
fluctuation molecular states;
conformational behavior;
molecular fields;
lipophilicity;
molecular complexity;
solute-solvent interactions;
ligand-receptor interactions;
molecular recognition;
emergent properties;
dissolvence
The immunoglobulin allotype contributed by peritoneal cavity B cells dominates in SCID mice reconstituted with allotype-disparate mixtures of splenic and peritoneal cavity B cells.
Authors: J E Riggs, R S Stowers, D E Mosier
Journal: The Journal of Experimental Medicine (1990)

We have studied potential regulatory interactions between mature B lymphocyte populations by analysis of C.B-17 severe combined immunodeficient (SCID) mice reconstituted simultaneously with immunoglobulin allotype-congenic mixtures of spleen (SP) and peritoneal cavity (PerC) B cells. We have previously shown that the independent transfer of B cells from these sources leads to the long-term survival of donor B cells and reconstitution of immunoglobulin levels in SCID mice (Riggs, J.E., D.L. Robertson, R.S. Stowers, and D.E. Mosier, manuscript submitted for publication). SP and PerC B cells differ in numerous respects, with the PerC having higher proportions of large, activated B cells that express the IgM greater than IgD phenotype and greater numbers of CD5 B cells. The injection of equal numbers of B cells from SP and PerC into SCID recipients (e.g., BALB/c SP + C.B-17 Per C----SCID) has led to the following observations: (a) serum IgM allotypes in B cell chimeras revealed strict dominance by the allotype contributed by the PerC B cells; (b) this dominance was not due to regulatory T cells; (c) B cells of the unexpressed (i.e., SP) allotype were present in the chimera in the spleen but not the peritoneal cavity; and (d) immunization with TI and TD antigens failed to elicit the SP IgM allotype, whereas secondary TD antigen immunization elicited low levels of the SP IgG2a allotype. Additional experiments demonstrated concurrent expression of IgM allotypes derived from both SP and PerC B cells in recipients that: (a) received a 10-fold excess of SP B cells; (b) received SP B cells before PerC B cell transfer; or (c) received SP B cells intravenously and PerC B cells intraperitoneally. We conclude that the establishment of IgM synthesis by PerC B cells leads to a feedback inhibition of subsequent IgM synthesis by SP B cells, and that the frequency of B cells that can lead to this effect is substantially higher in peritoneal cavity than in spleen. These data provide further confirmation of regulatory interactions between B cells in the absence of T lymphocytes, but confound the interpretation of experiments supporting the existence of a separate CD5+ B cell lineage.
Is the obesity epidemic exaggerated? No
Authors: R W Jeffery, N E Sherwood
Journal: BMJ (2008)

The UK health secretary declared last week that we are in the grip of an obesity epidemic. <b>Patrick Basham</b> and <b>John Luik</b> believe that the problem is less clear cut, but <b>R W Jeffery</b> and <b>N E Sherwood</b> say that obesity is a growing global problem
Third generation oral contraceptives-- the controversy
Authors: D. Carnall, H. Karcher, L. G. Lie, T. Sheldon, D. Spurgeon, D. Josefson, C. Zinn
Journal: BMJ (1995)

In October 1995 unpublished data were released in Great Britain which suggested that the risk of venous thromboembolism doubled in users of oral contraceptives (OCs) containing the newer progestogens desogestrel and gestodene.  As a result of this publicity the British Committee on Safety of Medicines decided to inform women of the apparently increased risk.  The German Federal Institute for Medical Drugs on the other hand incurred the criticism of physicians and the pharmaceutical industry by restricting use of the newer combination OCs to first-time users under the age of 30.  In Norway the Medicines Control Authority warned women not to use the only available brand containing a new progestogen unless they were dissatisfied with other brands of OC.  The Dutch Medicines Assessment College adopted a wait and see approach as did the Canadian Federal Drugs Directorate.  The US Food and Drug Administration reviewed the three studies and concluded that the minimal risk reported did not warrant asking women to switch brands of OCs.  In Australia scant media attention was given to the British scare and no official action was taken other than a routine review of all warnings and cautions.
Critical illness polyneuropathy: clinical findings and cell culture assay of neurotoxicity assessed by a prospective study
Authors: A. Druschky, M. Herkert, M. Radespiel-Tröger, K. Druschky, E. Hund, C.-M. Becker, M.J. Hilz, F. Erbguth, B. Neundörfer
Journal: Intensive Care Medicine (2001)
Europe's drug agency will publish clinical trial data for new products from 2014
Authors: I. Torjesen
Journal: BMJ (2012)

The European Medicines Agency has committed itself to publishing full clinical trial data submitted by companies for a clinical product once it has recommended granting marketing authorisation for that product.

The commitment will apply only to products that complete the marketing authorisation process from a set date, expected to be 1 January 2014. It will not apply to products granted marketing authorisation before this date.



 

This means that the agency will not have to make data available on cases of sudden death after a first dose of the multiple sclerosis drug fingolimod or safety data on …
Public Health Response for the 1996 Olympic Games
Authors: Patrick Meehan, Kathleen E. Toomey, James Drinnon, Samuel Cunningham, Nancy Anderson, Edward Baker
Journal: JAMA (1998)

Extensive planning and preparation by public health agencies were required for the provision of public health services during the 1996 Centennial Olympic Games, which brought together more than 10000 athletes from 197 countries and more than 2 million visitors. Public health activities included the development and use of an augmented surveillance system to monitor health conditions and detect disease outbreaks; creation and implementation of 6 environmental health regulations; establishment of a central Public Health Command Center and response teams to coordinate response to public health emergencies; planning for potential mass casualties and the provision of emergency medical services; implementation of strategies for the prevention of heat-related illness; and distribution of health promotion and disease prevention information. Public health agencies should take the lead in organizing and implementing a system for preventing and managing public health issues at future large-scale public events such as the Olympics.
New roles for mitochondria in cell death in the reperfused myocardium
Authors: S.-B. Ong, A. B. Gustafsson
Journal: Cardiovascular Research (2011)

Mitochondria play an important role in regulating the life and death of cells. They provide the cell with energy via oxidative phosphorylation but can quickly turn into death-promoting organelles in response to stress by disrupting adenosine triphosphate synthesis, releasing pro-death proteins, and producing reactive oxygen species. Due to their high-energy requirement, cardiac myocytes are abundant in mitochondria and as a result, particularly vulnerable to mitochondrial defects. Myocardial ischaemia and reperfusion are associated with mitochondrial dysfunction and cell death. Therefore, future therapies will focus on preserving mitochondrial integrity and function in hopes of minimizing the impact of ischaemia/reperfusion (I/R) injury. It is well established that myocardial I/R activates both necrosis and apoptosis, and that blocking either process reduces the levels of injury. However, recent studies have demonstrated that alterations in mitochondrial dynamics or clearance of mitochondria via autophagy also can contribute to cell death in the myocardium. In this review, we will discuss these new developments and their impact on the role of cardiac mitochondria in cell death following reperfusion in the heart.
Human prolactin and thyrotropin concentrations in the serums of normal and hypopituitary children before and after the administration of synthetic thyrotropin-releasing hormone
Authors: Thomas P. Foley, Laurence S. Jacobs, William Hoffman, William H. Daughaday, Robert M. Blizzard
Journal: Journal of Clinical Investigation (1972)

Synthetic thyrotropin-releasing hormone (TRH) was administered to normal children and hypopituitary patients in a dose of 7 mug/kg i.v. over 30-60 sec. Serum thyrotropin (TSH) and prolactin (HPr) concentrations were measured by radioimmunoassay before and at 15-min intervals for 2 hr after TRH. In 20 normal children HPr rose from a mean baseline value of 7.0+/-1.2 (SEM) ng/ml to a mean peak value of 39.5+/-5 ng/ml. In 11 patients with growth hormone (GH) deficiency without TSH deficiency. HPr values rose from a mean baseline of 3.6+/-0.8 ng/ml to a mean peak value of 13.9+/-2.8, a significantly less peak response as compared with normal children (P < 0.005). The TSH responses to TRH, however, were statistically indistinguishable from those of normal children. In 10 patients with GH and TSH deficiency both the mean baseline HPr levels (25.0+/-5 ng/ml) and the mean peak HPr levels after TRH (68.5+/-10 ng/ml) were significantly higher (P < 0.005 and < 0.025) than those of normal children. Similar comparisons were also true for the peak TSH responses (P < 0.05). Two panhypopituitary patients released no TSH and only small amounts of HPr after TRH. After thyroid replacement therapy in eight of the patients with GH and TSH deficiency, the mean HPr baseline levels (7.6+/-1.0 ng/ml) and peak levels (23.3+/-4.6 ng/ml) after the same dose of TRH were significantly less than their pretreatment levels (P < 0.001 and < 0.01) and were within the range for normal children. Synthetic TRH stimulates the simultaneous release of TSH and HPr in normal children and most hypopituitary patients. When the concentrations of thyroxine (T4) and triiodothyronine (T3) are low, the levels of HPr before and after TRH are elevated. After thyroid replacement therapy, HPr levels decrease to normal. T4 and/or T3 may condition the production or effects of prolactin-inhibiting factor (PIF) activity. The TSH and HPr responses after TRH in hypopituitary patients will determine whether the primary defect resides in the pituitary or hypothalamus, but cannot delineate the hypothalamic defect as a deficiency of hypothalamic hormone production or neurohumoral transmission.
Lansley writes price competition out of the health bill
Authors: Z. Kmietowicz
Journal: BMJ (2011)

Hospitals in England will not be able to compete with each other on price when GP consortiums take charge of most of the NHS budget in April 2013, the health secretary has said.

In what is seen as an unusual step, Andrew Lansley has tabled an amendment to his own Health and Social Care Bill that removes powers from the regulator Monitor to set maximum tariffs for services that could have made it possible for providers to bid for contracts at a price below the standard NHS tariff. The changes also remove the ability to vary prices according to whether a provider is in public or private hands. …
Hepatic Mitochondrial Malondialdehyde Metabolism in Rats With Chronic Iron Overload
Authors: Robert S. Britton, Rosemary O'Neill, Bruce R. Bacon
Journal: Hepatology (1990)

Peroxidative decomposition of mitochondrial membrane phospholipids with subsequent mitochondrial dysfunctin is a postulated mechanism of liver cell injury in parenchymal iron overload. Malondialdehyde is formed when polyunsaturated fatty acids of membrane phospholipids undergo peroxidative decomposition, and it is metabolized by aldehyde dehydrogenase. We studied mitochondrial metabolism of malondialdehyde in rats with chronic dietary iron overload. Hepatic malondialdehyde concentrations were significantly increased in iron–loaded livers, and mitochondrial respiratory control ratios using glutamate as a substrate were decreased by 47% largely owing to reductions in state 3 respiration. When exogenous malondialdehyde was added to mitochondrial fractions, there was significantly less metabolism of malondialdehyde in mitochondria of iron–loaded livers as compared with controls. In addition, there was a 28% decrease in mitochondrial aldehyde dehydrogenase in iron–loaded livers but no change in cytosolic aldehyde dehydrogenase. Increased hepatic malondialdehyde in chronic iron overload may result from a combination of increased production and decreased metabolism of malondialdehyde, both of which may be due to ironinduced mitochondrial lipid peroxidation.
Drug treatment of breathlessness: contrasting effects of diazepam and promethazine in pink puffers.
Authors: A A Woodcock, E R Gross, D M Geddes
Journal: BMJ (1981)

<h3>Objective:</h3> To present a case report of hyperbaric oxygen as potential therapy for radiation induced plexopathy. <h3>Background:</h3> Radiation induced plexopathy results after radiation treatment is targeted at pelvic malignancies. It typically presents with motor and sensory changes in lower extremities (LEs), although, due to the various anatomic sites that are irradiated, the presentation can vary. RIP is a rare but severe side effect that can impact quality of life and is usually a diagnosis of exclusion. To date there is no effective treatment. We report a case in which hyperbaric oxygen (HBO) treated RIP. <h3>Design/Methods:</h3> n/a <h3>Results:</h3> A 64-year-old man with history of prostate cancer status post 39 radiation treatments reported progressive bilateral LE parasthesias and weakness a few months after radiation. His examination showed mild diffuse weakness in bilateral LEs and decreased sensation in patchy distribution in bilateral LEs and saddle region. EMG showed bilateral thoracic radiculopathy, L5 radiculopathy and S1 radiculopathy. MRI of the entire spine was unremarkable. CSF analysis was negative for malignant, infectious or inflammatory etiologies. Therefore, symptoms were attributed to radiation induced plexopathy. He was started on hyperbaric oxygen therapy. After completing 24 treatments, patient reported improvement in symptoms. Bilateral lower extremity and saddle anesthesia had resolved. He also had improvement in lower extremity strength. <h3>Conclusions:</h3> Radiation-induced plexopathy (RIP) is a rare side effect of radiation that can lead to significant disability and difficulty in performing activities of daily living. Due to increasing survival rates of cancer patients, the incidence of RIP has increased as well. At this time, RIP is typically thought to be irreversible and management is primarily supportive care. Our patient with RIP was treated with hyperbaric oxygen therapy and had significant improvement in symptoms. Given the impairment in function this condition can cause, we suggest a trial of HBO be considered for all patients with RIP. <b>Disclosure:</b> Dr. Verma has nothing to disclose. Dr. Goldschmidt has nothing to disclose. Dr. Vaughan has nothing to disclose.
Do selective serotonin reuptake inhibitors cause suicide?: Authors' reply to Jones, Sakinofsky and Streiner, and Mitchell
Authors: Dean Fergusson, Steve Doucette, Paul Hebert, David Healy, Stan Shapiro
Journal: BMJ (2005)

Do selective serotonin reuptake inhibitors cause suicide? Risk of suicide should be assessed for whole class of antidepressantsEditor-Gunnell et al's report on suicide risk with selective serotonin reuptake inhibitors (SSRIs) raises several issues. 1 Firstly, clinicians have observed that the first weeks of treatment of severe depression with an antidepressant are accompanied by a higher risk of suicide because of a drug induced motor disinhibition that is not yet accompanied by mood improvement. 2 Secondly, the authors' finding of a trend towards a protective effect of SSRIs against suicidal thoughts (odds ratio 0.77) compared with a trend towards an increased risk of self harm (odds ratio 1.57) is paradoxical.More surprising is the heterogeneity of results among SSRIs.Why would sertraline show a protective effect for suicidal thoughts and simultaneously increase the risk of self harm?The risk difference between citalopram and its active S-enantiomere, escitalopram, is also strange.No strong biological rationale can explain such heterogeneity among drugs with the same mechanism of action.Thirdly, the authors mention that the Medicine and Healthcare products Regulatory Agency found little evidence for a risk difference between SSRIs and the other antidepressants.The two accompanying papers show that the suicidal risk seems similar for serotoninergic and tricyclic antidepressants. 3 4The risk of suicide must be assessed for the whole class of antidepressants.The next stage would be to measure the risk of suicide according to the time since starting an antidepressant.Initially, the risks are higher than the benefits.To confirm old clinical observations by evidence based methods would be interesting and useful.
Four Cases of Obstruction at the Duodeno-jejunal Junction
Authors: F. A. R. Stammers
Journal: BMJ (1952)

B=Tm 1013 of the latter group 9.6% developed demonstrable lesions.But when the 9.6% of students were analysed further, 6.2% were regarded as primary complexes and pleurisy and only 3.4% as reinfection lesions, a figure similar to the 3.1% of