tbuckley/cabot-search huggingface dataset:
Differential Response to Cardiac Resynchronization Therapy and Clinical Outcomes According to QRS Morphology and QRS Duration
Authors: Matthias Dupont, John Rickard, Bryan Baranowski, Niraj Varma, Thomas Dresing, Alaa Gabi, Michael Finucan, Wilfried Mullens, Bruce L. Wilkoff, W.H. Wilson Tang
Journal: Journal of the American College of Cardiology (2012)
Potent antagonism of calmodulin activity in vitro, but lack of antiproliferative effects on keratinocytes by the novel leukotriene biosynthesis inhibitor MK-886
Authors: L. HEGEMANN, A. HATZELMANN, S. GREWIG, B.H. SCHMIDT
Journal: British Journal of Dermatology (2006)

MK-886, a leukotriene biosynthesis inhibitor, which prevents the translocation and activation of 5-lipoxygenase, has been proposed as an effective drug for the treatment of inflammatory disorders, including psoriasis. In the present study, we investigated the effects of MK-886 on calmodulin as a potential target protein of anti-inflammatory drug activity, and on the proliferation of cultured human keratinocytes, a calmodulin-dependent cellular response with indicative value for antipsoriatic drug activity. Despite potent calmodulin-antagonistic activity in vitro, MK-886 failed to block cell proliferation in a human keratinocyte line, whereas trifluoperazine, a well characterized calmodulin antagonist with similar effects on calmodulin activity in our in vitro assays, inhibited cell proliferation in a dose-dependent manner. Further investigations on the mechanism of action revealed that, in contrast with trifluoperazine, calmodulin antagonism by MK-886 in vitro is likely to be mediated at the level of the allosteric calmodulin-recognition site of phosphodiesterase, rather than by binding to calmodulin itself. Therefore, our data do not conflict with the proposed role of calmodulin in the regulation of cell proliferation, but demonstrate that drug-induced antagonism of calmodulin, detected by inhibition of calmodulin-dependent enzymes in vitro, is not necessarily linked to antiproliferative activity in human keratinocytes.
Allergic Reactions to Penicillin
Authors: R. A. M. Scott
Journal: BMJ (1947)

to reject Government aid.Chlemists will have no Governmentfranked prescriptions.Doctors will have no Government pay.Patients, hospitals, chemists, and doctors will have less money.The standard of medical care will inevitably fall, nor has the B.M.A. been able so far to persuade the Divisions to agree to any scheme of organization of what care will be available.Dr. Hill said: " The doctors will be loyal to their calling and to their patients, to whom as always they owe their first duty."And all this because of a majority of 3,496 out of 56,671.There must be an Amending Act, a
Therapeutic bronchoscopy with immediate effect: laser, electrocautery, argon plasma coagulation and stents
Authors: C. T. Bolliger, T. G. Sutedja, J. Strausz, L. Freitag
Journal: European Respiratory Journal (2006)

Minimally invasive diagnostic and therapeutic approaches in medicine have been applied for a more selective and tailored approach to reduce patients' morbidity and mortality. The efficacy of interventional pulmonology for palliation of patients with central airways obstruction has been established and its curative potential for intralesional treatment of early cancer has raised great interest in current screening programmes. This is due to the fact that surgical resection and systemic nodal dissection as the gold standard is relatively morbid and risky, especially when dealing with individuals with limited functional reserves due to smoking-related comorbidities, such as chronic obstructive pulmonary disease. Furthermore, such comorbidities have been proven to harbour early stage lesions of several millimetres in size without involvement of nodal disease that may be amenable to local bronchoscopic treatment. Therefore, the success of minimally invasive strategies for palliation and treatment with curative intent strongly depends on the diligent identification of the various factors in lung cancer management, including full comprehension of the limits and potential of each particular technique. Maximal preservation of quality of life is a prerequisite in successfully dealing with individuals at risk of harbouring asymptomatic early lung cancer, to prevent aggressive surgical diagnostic and therapeutic strategies since overdiagnosis remains an issue that is heavily debated. In the palliative setting of alleviating central airway obstruction, laser resection, electrocautery, argon plasma coagulation and stenting are techniques that can provide immediate relief, in contrast to cryotherapy, brachytherapy and photodynamic therapy with delayed effects. With curative intent, intraluminal techniques that easily coagulate early stage cancer lesions will increase the implementation of interventional pulmonology for benign and relatively benign diseases, as well as early cancer lesions and its precursors at their earliest stage of disease.
Understanding Global Health
Authors: C. Donald Combs
Journal: Annals of Internal Medicine (2008)

Medical Writings: Book Notes16 September 2008Understanding Global HealthC. Donald Combs, PhDC. Donald Combs, PhDFrom Eastern Virginia Medical School, Norfolk, Virginia.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-149-6-200809160-00024 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Understanding Global HealthMarkle W, Fisher M, Smego, R. 384 pages. New York: McGraw-Hill; 2007. $36.95. ISBN 9780071487849. Order at www.mhprofessional.com.Field of medicine: Global health.Format: Softcover book.Audience: Clinicians, medical professionals, and students with an interest in global health.Purpose: To provide health professionals with a readable, authoritative, and practical volume that will help them understand current and future global health problems.Content: Chapters are organized from general consideration of global health to more specific consideration of such issues as environmental health, nutrition, injury, HIV/AIDS, emerging diseases, aging populations, and chronic illness. Each chapter begins with learning objectives ... Author, Article, and Disclosure InformationAffiliations: From Eastern Virginia Medical School, Norfolk, Virginia. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 16 September 2008Volume 149, Issue 6Page: 440KeywordsEnvironmental healthGlobal healthHealth careHealth economicsNutritionObstetrics and gynecologyPopulation statisticsPrevention, policy, and public healthPrimary careSoftware tools ePublished: 16 September 2008 Issue Published: 16 September 2008 Copyright & PermissionsCopyright © 2008 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
PITRESSIN TANNATE IN OIL IN THE TREATMENT OF DIABETES INSIPIDUS
Authors: HARRY BLOTNER
Journal: JAMA (1942)

The effects and disadvantages of solution of posterior pituitary and of pitressin administered hypodermically or intranasally in relieving the symptoms of diabetes insipidus are well known. The subcutaneous injection of the drug causes local irritation and is frequently followed by intestinal cramps, diarrhea, headaches, palpitation and pallor. Moreover, the therapeutic effect is temporary, lasting only a few hours. In order to control a patient's symptoms by this method, it is necessary to inject the drug three, four or more times a day. The intranasal use of solution of posterior pituitary and of pitressin appears to be somewhat more satisfactory because it avoids the necessity of injection and can be taken easily a number of times a day. Again, however, the effect lasts only for several hours. Frequently patients become sensitive to the drug intranasally with resultant sneezing, irritation of the nose and a mucous discharge and diminished absorption.  A compound
Collagen antibody-induced arthritis (CAIA) leads to evoked and ongoing persistent pain-like behavior, but transient joint inflammation
Authors: K Sandor, K S Nandakumar, R Holmdahl, M Björnholm, R Tom, A Krook, C I Svensson
Journal: Annals of the Rheumatic Diseases (2012)

Backgroundand objectives Joint pain is one of the most common types of persistent pain, and it is frequently reported to be a bothersome symptom by rheumatoid arthritis (RA) patients. RA is a chronic autoimmune inflammatory disease characterised by joint swelling, stiffness, and cartilage and bone erosion. Currently there are few effective treatments for persistent pain conditions, thus, it is important to increase our understanding of chronic pain mechanisms. The collagen type II antibody-induced arthritis (CAIA) model is commonly used in the rheumatology field. This model is based on injection of monoclonal antibodies against CII, which induces arthritis-like symptoms and a joint pathology that resembles human RA. However, CAIA has not been evaluated as a model of arthritis-induced pain. Hence, our aim was to characterise CAIA from a pain perspective. Materials and methods B10.RIII male mice were injected intravenously with collagen antibody cocktail (CAIA group) or saline on day 0 (control group). The CAIA group received lipopolysaccharide (LPS) and the control group saline intraperitoneally on day 5. Another group received intravenous saline followed by intraperitoneal LPS (LPS group). The degree of arthritis was assessed by visual scoring of the paws and evoked nociception by von Frey filament testing for 70 days. Ongoing pain-like behaviour (locomotion) was monitored for 48 h at two occasions and the antinociceptive effect on locomotion of the opioid buprenorphine (0.1 mg/kg intraperitoneal) was investigated. Spinal mRNA levels of inflammatory mediators were measured by real-time quantitative PCR. Results CAIA mice displayed transient signs of arthritis, while mechanical hypersensitivity was observed prior to and outlasting reversal of joint inflammation. The LPS group showed reduced nociceptive thresholds only the day after LPS injection. Locomotion was reduced both during and after inflammation in the CAIA group, which was reversed by buprenorphine in both phases. Interestingly, the mRNA level of IL-1β was elevated in the spinal cord during both phases, while other inflammatory mediators, such as tumour necrosis factor and high mobility group box 1 (HMGB1) were elevated only during the post-inflammatory phase. Conclusions This study demonstrates that CAIA generates robust and highly reproducible hypersensitivity, making this model suitable for studies of joint pain driven by antibody-mediated inflammation, both during peak and remittent phases of RA. Our findings also indicate that peripheral joint inflammation drives time-dependent spinal cytokine synthesis.
Remethylation and transsulfuration of methionine in cirrhosis: Studies with l-[2H3-methyl-1-13C]methionine
Authors: Stefan Russmann, Edith Junker, Bernhard H. Lauterburg
Journal: Hepatology (2002)

Disturbances of the methionine cycle may result in liver injury. Patients with alcohol-induced liver disease often exhibit hypermethioninemia and a delayed clearance (CL) of methionine, but the extent to which transsulfuration and remethylation pathways of the cyclic methionine metabolism are affected is unknown. Methionine turnover was determined in 7 healthy volunteers and 6 patients with alcohol-induced cirrhosis after oral administration of 2 mg/kg [(2)H(3)-methyl-1-(13)C]methionine, which permitted us to follow transsulfuration by its decarboxylation to (13)CO(2) and remethylation by replacement of the labeled methyl group by an unlabeled one. Basal plasma concentrations of endogenous methionine (50 +/- 5 vs. 25 +/- 2 micromol/L, mean +/- SEM, P <.001) were significantly higher in patients with cirrhosis and its CL was significantly decreased (774 +/- 103 vs. 2,050 +/- 141 mL/min, P <.001). Methionine turnover amounted to 42 +/- 4 vs. 27 +/- 3 micromol/kg/h (P <.05) in controls and patients with cirrhosis, respectively. The fraction of administered methionine undergoing remethylation was lower in patients with cirrhosis (7.6 +/- 1.5 vs. 14.1 +/- 1.1%, P <.005). However, because of the larger pool of circulating methionine, the total flux of methionine through the remethylation pathway was similar in both groups. A significantly lower fraction of the administered dose appeared in the form of (13)CO(2) in breath in patients with cirrhosis (2.2 +/- 0.4 vs. 11.0 +/- 0.8%, P <.001). In conclusion, the data indicate that the liver with cirrhosis compensates for a decreased activity of remethylating enzymes by operating at higher concentrations of methionine. In contrast, transsulfuration is impaired in patients with alcohol-induced cirrhosis such that an assessment of transsulfuration by a simple breath test may provide a clinically useful estimate of hepatic function.
Patients, Primary Care Physicians, and Payments for Hospital Visits-Reply
Authors: J. Trig Brown
Journal: JAMA (1997)

<h3>In Reply.</h3> —Dr Paulshock and I agree that primary physicians hold information crucial to their patient's care, both in the hospital and out of it. She asks about how we should be reimbursed for contributing this necessary information, but I do not have the answers to all her important questions. I would respond with one of my own: should our profession look to outside payers to define our roles in patient care? Was I paid for my visits? The answer depends on one's point of view.
Effect of simvastatin, an inhibitor of hydroxy-methylglutaryl coenzyme a reductase, on the growth of human ito cells
Authors: Ariane Mallat, Anne-Marie Preaux, Sylvie Blazejewski, Daniel Dhumeaux, Jean Rosenbaum, Philippe Mavier
Journal: Hepatology (1994)

During hepatic fibrogenesis, Ito cells proliferate, acquire a myofibroblastlike phenotype and synthesize increased amounts of extracellular matrix components. In this study, we have assessed the effects of simvastatin, an inhibitor of hydroxy-methylglutaryl-coenzyme A reductase, on the growth of human myofibroblastlike Ito cells. Cells were grown from explants of normal human liver and characterized by a positive staining for desmin and smooth muscle α-actin. Simvastatin (0.1 to 10 μmol/L) induced a marked dose-dependent decrease of [ 3 H]thymidine incorporation in human Ito cells, whether stimulated by human serum or by purified growth factors. Simvastatin-induced inhibition of DNA synthesis was confirmed by nuclear autoradiography and was not explained by a cytotoxic effect. The growth inhibitory effect of simvastatin was specifically due to inhibition of hydroxy-methylglutaryl-coenzyme A reductase because it was overcome by addition of mevalonic acid, the product of the enzymatic reaction. The reduction in [ 3 H]thymidine incorporation was not affected by supplementation of culture medium with purified cholesterol-low-density lipoprotein or isopentenyl adenine. It was partially reversed by addition of farnesol. These results show that simvastatin decreases the growth of human Ito cells, independently of its effect on cholesterol synthesis. This decrease may be due in part either to reduced farnesylation of proteins involved in growth factor signaling pathway or to inhibition of N-linked protein glycosylation. Whether this effect exists in vivo and could thus lead to a parallel decrease of fibrosis deposition within the liver requires further study. (Hepatology 1994;20:1589-1594).
Regulators can challenge deals that delay generic competition, says US Supreme Court
Authors: M. McCarthy
Journal: BMJ (2013)

The US Supreme Court ruled on 17 June that government regulators could sue drug companies for antitrust violation when they entered into “pay to delay” deals that often kept low cost generic drugs off the market.

Under US law a company can seek approval for a generic version of a brand name drug without conducting its own clinical trials if it can show the Food and Drug Administration that the drug has the same active ingredients and is biologically equivalent and it assures the FDA that the generic product does not violate the brand name drug’s patents.

The manufacturers of the brand name drugs often seek to delay or block such approvals by filing a suit claiming patent infringement. But many such suits end with what are known as “reverse payment” settlements in which the patent holder pays the generic drug maker for promising that it will not introduce its …
Plasma Vasoconstrictor Activity in Patients with Renal, Malignant, and Primary Hypertension
Authors: ANNETTE E. FITZ, MARK L. ARMSTRONG
Journal: Circulation (1964)

Polypeptide vasoconstrictor activity was assayed in the peripheral venous blood of 45 hypertensive patients and 20 normal subjects. The average activity was significantly increased in all hypertensive groups, and activity tended to be much higher in patients with renovascular and malignant hypertension than in primary hypertension. In confirmation of previously reported results by Helmer and Judson, there was no correlation between vasoconstrictor activity and renal excretory function. The plasma level of vasoconstrictor activity did not correlate with mean arterial pressure except when malignant or renovascular hypertension was present. A significant inverse relationship was found between the serum potassium concentration and vasoconstrictor activity: as activity levels increased, the potassium fell. The data suggest that a renin-like substance may be present in various hypertensive states in amounts sufficient to depress serum potassium, presumably by activation of the renin-angiotensin-aldosterone mechanism.
Enhanced levels of both the membrane-bound and soluble forms of IgM Fc receptor (FcμR) in patients with chronic lymphocytic leukemia
Authors: Fu Jun Li, Yoshiki Kubagawa, Matthew K. McCollum, Landon Wilson, Tomoko Motohashi, Luigi F. Bertoli, James C. Barton, Stephen Barnes, Randall S. Davis, Hiromi Kubagawa
Journal: Blood (2011)
THE TRANSPLANTATION OF BONE
Authors: W. E. Gallie
Journal: BMJ (1931)

Pericardial effusion markedly decreased.January 12/th: Hardly any effusion noted ; lungs practically clear.February 6th: Much better.Area of cardiac dullness normal; at apex, systolic murmur still heard and second sound reduplicated; pulmonary second sound accentuated.March 2nd: No-reduplication of apical second sound now present, otherwise physical signs in heart unchanged.March 3rd: Some pain in left shoulder, and rise of temperature and pulse rate.March 7th: Patient seemed very well.Pulse rate 88 to 90.Condition of heart as above; apex beat not fixed, and- no other signs of adherent pericardium.Liver not enlarged.About a veek later the boy was discharged to a con- valescent home.He was treated with sodium salicylate while in hospital.CASE II S. H., female, aged 8. Family history was negative.
VIRUSES OF POLIOMYELITIS
Authors: James D. Trask, John R. Paul, Agnes R. Beebe, William J. German
Journal: The Journal of Experimental Medicine (1937)

Qualitative immunological differences exist between early passage strains or so called human strains of the virus of poliomyelitis. These differences show a relationship to the epidemic source of the virus and are exemplified in this study by 4 strains isolated in different years during an eastern and western epidemic of poliomyelitis.
Co-proxamol is effective in chronic pain
Authors: G W Hanks, K. Forbes
Journal: BMJ (1998)

EDITOR—Li Wan Po and Zhang's review substantiates the widely held view that paracetamol is as effective as co-proxamol in single dose for acute pain.1 We agree with their message; indeed, another recent systematic review comes to the same conclusion.2

The authors dismiss comments we have made about the use of co-proxamol.3 However, our remarks related to the treatment of chronic pain, which cannot and should not be managed with …
"Alarming" report shows NHS finances are diving into the red
Authors: I. Torjesen
Journal: BMJ (2014)

The NHS in England is on the brink of deficit, and trusts responsible for hospitals and other services are already spending more than they receive from commissioners, says a report published by the National Audit Office.1

It says that the overall NHS surplus has fallen by two thirds in the space of a year, from £2.1bn (€2.7bn; $3.4bn) in 2012-132 to £722m in 2013-14, and that the NHS is forecasting a net deficit of £45m this financial year (2014-15).

In 2013-14 NHS England and clinical commissioning groups had a net surplus of £813m, while provider trusts ended the financial year £91m in deficit. By contrast, in 2012-13 provider trusts returned a surplus of £592m. A deficit was reported at the end of 2013-14 by 82 of the 456 NHS trusts, foundation trusts, and clinical commissioning groups in England. …
Predictors of Referral for Specialized Psychosocial Oncology Care in Patients With Metastatic Cancer: The Contributions of Age, Distress, and Marital Status
Authors: Janet Ellis, Judy Lin, Andrew Walsh, Christopher Lo, Frances A. Shepherd, Malcolm Moore, Madeline Li, Lucia Gagliese, Camilla Zimmermann, Gary Rodin
Journal: Journal of Clinical Oncology (2008)

This study examines the rate and prediction of referral for specialized psychosocial oncology care in 326 patients with metastatic GI or lung cancer.Referral information was abstracted from medical records and hospital databases. Patients completed measures of psychosocial and physical distress and functioning.Routine referral occurred in 33% of patients, and in 42% and 44%, respectively, of those scoring high on measures of depression (Beck Depression Inventory [BDI]-II >or= 15) and hopelessness (Beck Hopelessness Scale >or= 8). Univariate analyses indicated that referral was associated with younger age, unmarried status, living alone, presence of more depressive symptoms, hopelessness, and attachment anxiety, and with less social support, self-esteem, and spiritual well-being (all P < .05). Among the significantly depressed (BDI-II >or= 15), 100% of those less than 40 years of age, but only 22% of those age 70 years or older were referred. Multivariate analyses indicated that referral was associated with younger age, unmarried status, and presence of more depressive symptoms. Moreover, increasing age was associated with a progressively lower likelihood of referral independent of the level of distress.Routine referral of patients with metastatic cancer for psychosocial oncology care was predicted by presence of more severe depressive symptoms, younger age, and unmarried status. The rate of referral progressively declined with each decade of age, even among those with significant distress. These findings are consistent with some aspects of Andersen's model of health care utilization. The extent to which referred patients represent those who are most likely to benefit deserves further investigation.
Profiling of Immune Response to Guide Cancer Diagnosis, Prognosis, and Prediction of Therapy
Authors: Stefan Ambs, Francesco M. Marincola, Magdalena Thurin
Journal: Cancer Research (2008)

The meeting was held to provide an overview of the most recent scientific achievements in the field of immunologically relevant biomarkers. These markers could be used to assess the risk of tumor recurrence or to predict the response to treatment, including immune-based therapies. Another focus was
Viability and Function of Preserved Red Cells
Authors: C. Robert Valeri
Journal: New England Journal of Medicine (1971)

PRESERVATION of human red cells is considered to be satisfactory when the red cells are circulating and functioning immediately after transfusion: this applies whether the preservation procedure involves a liquid medium with storage at 4°C, a freeze-preservation technic using various cryoprotective agents and storage at either −80 or −150°C or a combination of the liquid and freeze-preservation approaches. Blood for freezing is collected in one of several liquid preservatives — acid-citrate-dextrose (ACD), citrate-phosphate-dextrose (CPD), ACD plus adenine, or CPD plus adenine, with our without inosine; it is then frozen by one of a number of procedures, stored at either −80 . . .