tbuckley/cabot-search huggingface dataset:
Commentary: Does additional benefit justify additional costs of insulin analogues?
Authors: P. T. Sawicki
Journal: BMJ (2011)

Late in 2004, the German Health Ministry held a conference that aimed to improve outcomes and cost-benefit relations in the treatment of chronic diseases. The ministry was concerned that the increasing costs of treatment were not accompanied by an improvement in patient relevant outcomes. As a consequence, in 2005 the Joint Federal Committee—the top decision body of the German healthcare system—commissioned the Institute for Quality and Efficiency in Health Care (IQWiG) with the assessment of diagnostic and therapeutic interventions in chronic diseases, including diabetes. In this context, the Institute assessed the additional benefit of short and long acting insulin analogues compared with that achieved with human insulin.

The methods used by the Joint Federal Committee and IQWiG aimed to evaluate a direct proof of benefit with regard to patient oriented outcomes or valid surrogate parameters.1 2 They required such parameters to be assessed in appropriate randomised controlled clinical trials, and non-randomised observational studies were regarded …
Survey of HIV patients' views on confidentiality and non-discrimination policies in general practice
Authors: M Shaw, D Tomlinson, I Higginson
Journal: BMJ (1996)

In Kensington, Chelsea, and Westminster in 1993-4, general practices knew of 761 HIV positive patients but 1186 HIV positive residents consulted HIV services. This discrepancy hinders the establishment of a therapeutic relationship and prevents primary health care teams gaining experience.

Patients may not believe that general practice is secure for confidential information. Therefore as part of a larger questionnaire we asked patients positive for HIV whether in general they were willing to disclose their diagnosis to practice staff, and then if they would be willing for all staff to know their diagnosis if there was a confidentiality or non-discrimination policy displayed at the practice.

All 1058 surviving HIV patients who attended outpatients departments between October 1992 and March 1994 were approached. We contacted 847 (80%); 170 patients were lost to follow up and 41 were physically …
Crosstalk between microRNA30a/b/c/d/e-5p and the Canonical Wnt Pathway: Implications for Multiple Myeloma therapy
Authors: Jian-Jun Zhao, Ruben D. Carrasco
Journal: Cancer Research (2014)

Dysregulation of transcription via the Wnt/β-catenin signaling pathway underlies the pathogenesis of a wide variety of frequent human cancers. These include epithelial carcinomas such as colorectal cancer and hematologic malignancies such as multiple myeloma. Thus, the Wnt/β-catenin in pathway potentially offers an attractive target for cancer therapy. This approach, however, has thus far proved challenging because the pathway plays a number of critical roles in physiologic homeostasis, [corrected] and because drugs that broadly target the pathway have unacceptable side effects. miRNAs function as regulators of gene expression and have also been implicated in the pathogenesis of multiple myeloma and other human cancers, offering the promise of novel therapeutic approaches if they can be applied effectively in vivo. Because BCL9 is a critical transcriptional coactivator of β-catenin that is aberrantly expressed in many human cancers but is of low abundance in normal tissues, [corrected] the Wnt/β-catenin/BCL9 complex has emerged as a promising and most likely relatively safe therapeutic target in cancers with dysregulated Wnt/β-catenin activity. This review discusses recent advances in the biology of Wnt inhibitors and the appealing possibility of a functional link between BCL9 and miRNA30a/b/c/d/e-5p that could be exploited for multiple myeloma therapy.
Comment: The Unidisciplinary vs the Multidisciplinary Approach to Oncology
Authors: Philip Rubin
Journal: JAMA (1971)

The medical literature dealing with cancer should be rewritten. Prior to this, however, the practice of oncology will have to change. It is undergoing change slowly but steadily, and the direction is that of carefully planned prospective treatment of cancer. Among physicians, a reawakening that they can do better is beginning to occur. Advances may be small and in different disciplines, but added together, they can yield as much as  breakthroughs.  In order for these breakthroughs to be realized there must be careful studies which are cooperative in nature. Today, such studies are viewed as gigantic national efforts with many universities and cancer centers participating. Surprisingly, members of the same specialty have demonstrated a capacity to meet and organize for scientific work on a national level; however cooperation within a single institution by all members of an oncology team is generally lacking, even in most major university hospitals. The
TETANUS.ITS PERIOD OF INCUBATION AND ITS PATHOLOGY.
Authors: ALBERT WOLDERT
Journal: JAMA (1904)

While I am not engaged in the special work of a surgeon, I have, on account of the various interesting features presented, often been tempted to place on record a certain case of tetanus treated a number of years ago. In view of the fact that the annual visitation of this disease has been brought on through the Fourth of July celebrations, and since the subject of the pathology as well as the treatment has assumed considerable prominence, and asThe Journalof the American Medical Association, June 18, 1904, page 1625, requests reports of cases of tetanus, I herewith comply with that request. On account of the bearing which this case may have on the pathology, especially the latent period or the power of storing up by the nervous system of the specific toxin, I desire to draw attention to the special article inThe Journalfor June 18
Caspase activation is required for antiviral treatment response in chronic hepatitis C virus infection
Authors: Xandra Volkmann, Markus Cornberg, Heiner Wedemeyer, Frank Lehner, Michael P. Manns, Klaus Schulze‐Osthoff, Heike Bantel
Journal: Hepatology (2006)

Only half of patients with chronic hepatitis C virus (HCV) infection and genotype-1 show a sustained antiviral response to the current antiviral therapy. The reason this treatment fails is unclear, and no reliable marker exists that predicts the treatment outcome. In the present study, we investigated the apoptotic activation of caspases in HCV patients undergoing antiviral therapy with regard to the treatment outcome. We determined caspase activation in sera from patients who were either responding or nonresponding to antiviral therapy by using two novel caspase assays, an immunological and a luminometric enzyme test. We found that compared with nonresponding individuals, responding patients showed significantly (P < .05) increased caspase activity, which was closely correlated with virus elimination (r = 0.81). The cutoff value of serum caspase activity was determined, which correctly predicted the treatment outcome with a sensitivity of 70% and a specificity of 82% (area under the curve 0.845; 95% CI). In conclusion, hepatic caspase activity might play a role in HCV clearance and could also predict the efficacy of antiviral therapy. (HEPATOLOGY 2006;43: 1311–1316.)
The Medical Profession and Public Life
Authors: V. Jackson
Journal: BMJ (1889)

was founded April, 1874, in consequence of a very general desire that this county should possess a medical society, for until the Branch was established Staffordshire was without one, although nearly 300 medical men reside within its area.From time to time local societies had been established; these at first flourished, then dwindled, and finally ceased to exist, but as the want of a medical centre was at that period much felt, the only existing one being the North Staffordshire, and as heretofore all local efforts as regards permanency had failed, it was determined that an attempt should be made to promote the formation of a county medical society.This proposal was dis- cussed at a meeting of the North Staffordshire Medical Society, specially convened for the purpose, and the following resolution was unanimously adopted:The North Staffordshire Medical Society, after an independent existence of twenty-five years, wishing to extend its influence and usefulness, resolved at a meeting of members held at Stokeupon-Trent, on Thursday, April 7th, 1874, to amalgamate with the British Medical Association."In furtherance of that resolution, the medical profession of the county was invited to assemble in Stafford on Thursday, April 30th, 1874.The meeting was a large and representative one, the chair being occupied by Dr. Weaver, the President of the North Staffordshire Medical Society.The formation of a Staffordshire Branch of the British Medical Association was at once agreed upon.
Stuttering Caused by Gabapentin
Authors: Mehran Nissani
Journal: Annals of Internal Medicine (1997)

Letters1 March 1997Stuttering Caused by GabapentinMehran Nissani, MD and Eduard A. Sanchez, MDMehran Nissani, MDSt. John's Episcopal Hospital, Far Rockaway, NY 11691Search for more papers by this author and Eduard A. Sanchez, MDSt. John's Episcopal Hospital, Far Rockaway, NY 11691Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-126-5-199703010-00018 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:Gabapentin is an antiepileptic drug that has diverse complications and side effects, but an extensive review of the literature [1] failed to show stuttering as one of the complications [2, 3].A 58-year-old woman was recently hospitalized because of an intractable seizure. She had been taking Dilantin (Parke Davis, Morris Plains, New Jersey) as an antiepileptic drug. Gabapentin was administered, the seizures stabilized within a few days, and the patient was discharged.During a follow-up visit in the outpatient clinic, the patient presented with stuttering. The patient denied any history of stuttering. Gabapentin therapy was discontinued; 4 ...References1. Onslow M. Choosing a treatment procedure for early stuttering: issues and future directions. J Speech Hearing Res. 1992; 35:983-93. Google Scholar2. Messiha FS. Fluoxentine: adverse effects and drug–drug interactions. J Toxicol Clin Toxicol. 1993; 31:603-30. Google Scholar3. Watson JB. Improving the effectiveness of stuttering intervention: the journey continues. Folia Phoniatr Logop. 1994; 46:214-22. Google Scholar Author, Article, and Disclosure InformationAuthors: Mehran Nissani, MD; Eduard A. Sanchez, MDAffiliations: St. John's Episcopal Hospital, Far Rockaway, NY 11691 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited bySex Differences in Childhood Stuttering and Coexisting Developmental DisordersDrug-induced stuttering: A comprehensive literature reviewDrug-induced stuttering: A comprehensive literature reviewPregabalin-Associated Stuttering in a Patient With Complex Regional Pain SyndromeGabapentinVerworven stotterenStuttering during Management of Postherpetic Neuralgia -A case report-Verworven stotterenAntiepileptic drugsGabapentin 1 March 1997Volume 126, Issue 5Page: 410KeywordsAntiepileptic drugEpileptic seizuresOutpatient clinics ePublished: 15 August 2000 Issue Published: 1 March 1997 Copyright & PermissionsCopyright © 1997 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
In vivo equilibrium of proinflammatory IL-17+ and regulatory IL-10+ Foxp3+ RORγt+ T cells
Authors: Matthias Lochner, Lucie Peduto, Marie Cherrier, Shinichiro Sawa, Francina Langa, Rosa Varona, Dieter Riethmacher, Mustapha Si-Tahar, James P. Di Santo, Gérard Eberl
Journal: The Journal of Experimental Medicine (2008)

The nuclear hormone receptor retinoic acid receptor-related orphan receptor gamma t (RORgamma t) is required for the generation of T helper 17 cells expressing the proinflammatory cytokine interleukin (IL)-17. In vivo, however, less than half of RORgamma t(+) T cells express IL-17. We report here that RORgamma t(+) T alphabeta cells include Foxp3(+) cells that coexist with IL-17-producing RORgamma t(+) T alphabeta cells in all tissues examined. The Foxp3(+) RORgamma t(+) T alphabeta express IL-10 and CCL20, and function as regulatory T cells. Furthermore, the ratio of Foxp3(+) to IL-17-producing RORgamma t(+) T alphabeta cells remains remarkably constant in mice enduring infection and inflammation. This equilibrium is tuned in favor of IL-10 production by Foxp3 and CCL20, and in favor of IL-17 production by IL-6 and IL-23. In the lung and skin, the largest population of RORgamma t(+) T cells express the gammadelta T cell receptor and produce the highest levels of IL-17 independently of IL-6. Thus, potentially antagonistic proinflammatory IL-17-producing and regulatory Foxp3(+) RORgamma t(+) T cells coexist and are tightly controlled, suggesting that a perturbed equilibrium in RORgamma t(+) T cells might lead to decreased immunoreactivity or, in contrast, to pathological inflammation.
Noradrenergic Vascular Hyper-Responsiveness in Human Hypertension Is Dependent on Oxygen Free Radical Impairment of Nitric Oxide Activity
Authors: Giuseppe Lembo, Carmine Vecchione, Raffaele Izzo, Luigi Fratta, Dario Fontana, Gennaro Marino, Giovanni Pilato, Bruno Trimarco
Journal: Circulation (2000)

Background —Noradrenergic vascular hyper-responsiveness is a hallmark of essential hypertension. To evaluate whether nitric oxide plays a role in the enhanced vascular response to norepinephrine in hypertension, we examined 32 hypertensives and 28 normotensives who were distributed in 3 experimental series. Methods and Results —In the first series, we measured the forearm blood flow (FBF) response to a norepinephrine infusion under control conditions and during the infusion of l -N-monomethylarginine (L-NMMA). Norepinephrine evoked dose-dependent vasoconstriction that was greater in hypertensives than in normotensives (maximum FBF, −61±1 versus −51±1%; P &lt;0.01). During L-NMMA infusion, norepinephrine vasoconstriction was not modified in hypertensives; however, it was potentiated in normotensives (maximum FBF, −64±2%; P &lt;0.01). In the second series, we tested whether norepinephrine vasoconstriction could be affected by an antioxidant such as ascorbic acid. Norepinephrine vasoconstriction was blunted by ascorbic acid administration only in hypertensives (maximum FBF, −49±3 versus −63±2%; P &lt;0.01); the vasoconstriction became similar to that observed in normotensives. During ascorbic acid plus L-NMMA administration, the vascular response to norepinephrine increased to a similar extent in both study groups. To rule out the possibility that the effect of ascorbic acid on norepinephrine vasoconstriction could depend on adrenergic receptor–induced nitric oxide release, in the last series we inhibited endogenous nitric oxide and replaced it with an exogenous nitric oxide donor (sodium nitroprusside). Even in these conditions, ascorbic acid attenuated norepinephrine vasoconstriction only in hypertensives (maximum FBF, −50±2 versus −62±1%; P &lt;0.01). Conclusions —Our data demonstrate that noradrenergic vascular hyper-responsiveness in hypertension is dependent on an impairment of nitric oxide activity that is realized through norepinephrine-induced oxygen free radical production.
A Clinical Lecture on the Differential Diagnosis in Cases of Albuminuria
Authors: H. French
Journal: BMJ (1911)

ALBUMINURIA is the term used to denote the passave in the urine of preteid that is coagulable on boiling.More than one substance is included in the word " 1 albumen " in this sense, and there are varying proportions of serum albumen and serum globulin in different cases.So variable may be the relative amounts of these, not only in different diseases, but also in different cases of
RHEOLOGY OF HUMAN BLOOD. STUDIES ON THE FLOW OF FRESH VENOUS BLOOD AND OF CITRATED BLOOD THROUGH TUBING OF DIAMETERS BETWEEN 0.09 AND 0.20 CM
Authors: Paul Dreizen
Journal: Journal of Clinical Investigation (1962)

Numerous studies have demonstrated that the rheological properties of blood are anomalous, in particular, that rate of flow through cylindrical tubing is not related linearly to the imposed gradient in pressure and that the viscosity of blood increases at low rates of flow (1-10). These data, and similar data obtained by means of other viscometric methods (11-13), are characteristic of non-Newtonian flow (14) and necessitate that any study of the rheological properties of blood must examine the dependence of viscosity upon applied shearing stress.
TCT-594 Five year and Final Report of BioFreedom First-In-Man, a Randomized Trial comparing Polymer-Free BioFreedom™ stents with Durable Polymer Taxus Liberté™ Stents
Authors: Eberhard Grube, Ralf Mueller, Gerhard Schuler, Karl-Eugen Hauptmann, Joachim Schofer, RICARDO A. COSTA, Carlo Di Mario
Journal: Journal of the American College of Cardiology (2014)
Murine double minute 2 regulates Hu antigen R stability in human liver and colon cancer through NEDDylation
Authors: Nieves Embade, David Fernández-Ramos, Marta Varela-Rey, Naiara Beraza, Marcella Sini, Virginia Gutiérrez de Juan, Ashwin Woodhoo, Nuria Martínez-López, Begoña Rodríguez-Iruretagoyena, Francisco Javier Bustamante, Ana Belén de la Hoz, Arkaitz Carracedo, Dimitris P. Xirodimas, Manuel S. Rodríguez, Shelly C. Lu, José M. Mato, María L. Martínez-Chantar
Journal: Hepatology (2011)

Abstract Hu antigen R (HuR) is a central RNA-binding protein regulating cell dedifferentiation, proliferation, and survival, which are well-established hallmarks of cancer. HuR is frequently overexpressed in tumors correlating with tumor malignancy, which is in line with a role for HuR in tumorigenesis. However, the precise mechanism leading to changes in HuR expression remains unclear. In the liver, HuR plays a crucial role in hepatocyte proliferation, differentiation, and transformation. Here, we unraveled a novel mean of regulation of HuR expression in hepatocellular carcinoma (HCC) and colon cancer. HuR levels correlate with the abundance of the oncogene, murine double minute 2 (Mdm2), in human HCC and colon cancer metastases. HuR is stabilized by Mdm2-mediated NEDDylation in at least three lysine residues, ensuring its nuclear localization and protection from degradation. Conclusion : This novel Mdm2/NEDD8/HuR regulatory framework is essential for the malignant transformation of tumor cells, which, in turn, unveils a novel signaling paradigm that is pharmacologically amenable for cancer therapy. (Hepatology 2012)
Organophosphorus Insecticide Toxicity
Authors: H. H. Golz
Journal: JAMA (1965)

<h3>To the Editor:—</h3> In the April 12, 1965 issue ofThe Journal(<b>192</b>: 178-179) there appears an answer by Joseph H. Holmes, MD, to a question concerning the prevention of poisoning by organophosphorus insecticides such as parathion and malathion. Some 50 organic compounds of phosphorus have been registered as insecticides by the US Department of Agriculture. They are closely related pharmacologically; their principal action is the ability to inhibit cholinesterase. This capacity and, hence, the<i>toxicity</i>varies markedly between individual compounds. The practical effect is a wide range of<i>hazards</i>associated with the use of these compounds. Most of the insecticides of the organophosphorus type are moderately to markedly toxic and hazardous. Dr. Holmes' answer evidently was predicated upon the assumption that all organophosphate insecticides fall into this category. The questioner specifically mentioned parathion and malathion. These compounds happen to occupy positions at the extreme ends of the range of
Air Pollution–Mediated Susceptibility to Inflammation and Insulin Resistance: Influence of CCR2 Pathways in Mice
Authors: Cuiqing Liu, Xiaohua Xu, Yuntao Bai, Tse-Yao Wang, Xiaoquan Rao, Aixia Wang, Lixian Sun, Zhekang Ying, Liubov Gushchina, Andrei Maiseyeu, Masako Morishita, Qinghua Sun, Jack R. Harkema, Sanjay Rajagopalan
Journal: Environmental Health Perspectives (2013)

Background: Epidemiologic and experimental studies support an association between PM2.5 exposure and insulin resistance (IR). Innate immune cell activation has been suggested to play a role in the pathogenesis of these effects.Objectives: We sought to evaluate the role of CC-chemokine receptor 2 (CCR2) in PM2.5-mediated inflammation and IR.Methods: Wild-type C57BL/6 and CCR2–/– male mice were fed a high-fat diet and exposed to either concentrated ambient PM2.5 or filtered air for 17 weeks via a whole-body exposure system. We evaluated glucose tolerance and insulin sensitivity. At euthanasia, blood, spleen, and visceral adipose tissue (VAT) were collected, and inflammatory cells were measured using flow cytometry. We used standard immunoblots, immunohistochemical methods, and quantitative PCR (polymerase chain reaction) to assess pathways of interest involving insulin signaling, inflammation, and lipid and glucose metabolism in various organs. Vascular function was assessed using myography.Results: PM2.5 exposure resulted in whole-body IR and increased hepatic lipid accumulation in the liver, which was attenuated in CCR2–/– mice by inhibiting SREBP1c-mediated transcriptional programming, decreasing fatty acid uptake, and suppressing p38 MAPK activity. Abnormal phosphorylation levels of AKT, AMPK in VAT, and adipose tissue macrophage content in wild-type mice were not present in CCR2–/– mice. However, the impaired whole-body glucose tolerance and reduced GLUT-4 in skeletal muscle in response to PM2.5 was not corrected by CCR2 deficiency.Conclusions: PM2.5 mediates IR by regulating VAT inflammation, hepatic lipid metabolism, and glucose utilization in skeletal muscle via both CCR2-dependent and -independent pathways. These findings provide new mechanistic links between air pollution and metabolic abnormalities underlying IR.Citation: Liu C, Xu X, Bai Y, Wang TY, Rao X, Wang A, Sun L, Ying Z, Gushchina L, Maiseyeu A, Morishita M, Sun Q, Harkema JR, Rajagopalan S. 2014. Air pollution–mediated susceptibility to inflammation and insulin resistance: influence of CCR2 pathways in mice. Environ Health Perspect 122:17–26; http://dx.doi.org/10.1289/ehp.1306841
Renal failure and low-molecular-weight dextran.
Authors: T. Morgan, J. M. Little
Journal: BMJ (1967)

expectant mother from the benefit of such a drive ?Dr. P. E. Dipple (p.360) is at pains to defend the Clinistix test ; he may have over- looked my reference to it as a " useful screening test " (p.206).Nevertheless, being an enzyme test, it is subject to the influence of anti-enzymes such as uric acid.I have found urines with 40 mg./l00 ml.glucose or more negative to Clinistix, and in this way some cases of diabetes might pass undetected;
What does successful regulation look like?
Authors: T. Bloom
Journal: BMJ (2015)

Good regulation starts with a genuine need. Steele and colleagues (doi:10.1136/bmj.h1485) identify just such a need in describing the unregulated online market in human breast milk. Surveys reveal a burgeoning informal market, largely among mothers who aren’t eligible for milk from established milk banks. But the message that “breast is best” drowns out concerns about safety. Inadequate screening and handling of samples risks transmission of infectious disease and bacterial contamination. Health professionals are urged to support alternatives to breast feeding where needed, but Steele and colleagues argue that legal regulation is also required.

It’s widely understood that new antibiotics are needed to combat increasing resistance. But Peter …