tbuckley/cabot-search huggingface dataset:
Does Heparin Cofactor II Modulate Atherosclerosis and Restenosis?
Authors: Douglas M. Tollefsen
Journal: Circulation (2004)

eparin cofactor II (HCII) is a plasma protein in search of a physiological function. 1HCII inactivates thrombin by formation of a stable, bimolecular complex.Detection of these complexes in human plasma suggests that HCII inhibits thrombin in vivo. 2 Sulfated polysaccharides such as heparin and dermatan sulfate interact with HCII and increase the rate of thrombin inhibition more than 1000-fold.HCII is homologous to antithrombin, which inhibits not only thrombin but also factors Xa and IXa when bound to heparan sulfate synthesized by endothelial cells; by this mechanism, antithrombin may prevent thrombosis of intact blood vessels.Mutations in the antithrombin gene that decrease its expression by half are associated with an increased risk of venous thromboembolism. 1 Despite much effort on the part of many investigators, a convincing association between HCII deficiency and venous or arterial thrombosis has not been established. 3In animal studies, mice that completely lack HCII develop clots more rapidly in their carotid arteries after oxidative damage to the endothelium than do wild-type mice. 4This work provides direct evidence that HCII can have antithrombotic activity in vivo and draws attention to the arterial system as a potential target of action of HCII.Two clinical studies 5,6 reported in Circulation suggest that HCII may help to protect people from in-stent restenosis or carotid artery atherosclerosis.
Usefulness of alpha-fetoprotein response in patients treated with sorafenib for advanced hepatocellular carcinoma
Authors: Nicola Personeni, Silvia Bozzarelli, Tiziana Pressiani, Lorenza Rimassa, Maria Chiara Tronconi, Francesco Sclafani, Carlo Carnaghi, Vittorio Pedicini, Laura Giordano, Armando Santoro
Journal: Journal of Hepatology (2012)
PSEUDO-SCLEROSIS (DIFFUSE SCLEROSIS), WITH THE REPORT OF A CASE WITH NECROPSY.
Authors: CHARLES S. POTTS
Journal: JAMA (1905)

In 1883 Westphal<sup>1</sup>reported two cases presenting a symptom-complex resembling that of multiple sclerosis, but in which microscopic examination of the brain and cord gave negative results. To this condition was given the name pseudo-sclerosis. Since this time a number of cases (14) presenting this condition have been reported, mostly by German observers. It will be noted in reading the abstracts of these cases, which are given below, that the brain and cord in a number of them were unusually firm. A similar condition of hardness, although possibly more marked, is observed in another group of cases also presenting a symptom-complex resembling that of multiple sclerosis, in which microscopic examination of the brain and cord shows a proliferation of neuroglia and vascular disease. To this condition the term diffuse sclerosis has been applied, and a number of cases have been reported, mostly by German authors. As will be shown
The Circulating Lymphocyte—Its Role in Infectious Mononucleosis
Authors: LAWRENCE N. CHESSIN
Journal: Annals of Internal Medicine (1968)

This Combined Clinical Staff Conference presents some of the newer findings in basic biology of the lymphocyte and illustrates how investigational techniques of tissue culture, virology, immunology, and fine structural analysis have been useful in studying some salient clinical features in infectious mononucleosis. Recent clinical studies and findings are summarized. The proliferative potential of the circulating lymphocyte and the isolation and characterization of continuous lymphoid cell lines derived from peripheral blood of patients with infectious mononucleosis are discussed. The microbial isolation pattern from patients and specific host immunologic responses are presented in light of recently identified virus-like particles in cell lines derived from patients with infectious mononucleosis.
PD3-2-6: Interim safety results from the East/South East (E/SE) Asian subgroup of the open-label TRUST (TaRceva lUng cancer Survival Treatment) study of erlotinib for advanced non-small-cell lung cancer (NSCLC)
Authors: Keunchil Park, Jong-Seok Lee, Yi-Long Wu, Li Zhang, Ashley Cheng, Joseph Siu-Kie-Au, Narin Voravud, Abdul Muthalib, Mohd Ibrahim A. Wahid, Chih-Hsin Yang
Journal: Journal of Thoracic Oncology (2007)
Association of Recurrent Suicidal Ideation With Nonremission From Acute Mixed Mania
Authors: Joseph F. Goldberg, Jessica L. Garno, Andrew C. Leon, James H. Kocsis, Laura Portera
Journal: American Journal of Psychiatry (1998)

Objective:The authors' goal was to examine suicidality in relation to acute symptom remission in inpatients with mixed and pure bipolar disorder.Method:Using chart review of 184 adult inpatients with bipolar I disorder, the authors assessed patients' past and current suicidality, other psychopathology, treatment, and remission.Results:Past, current, and recurrent suicidality were significantly more common among patients with mixed mania than among those with pure mania. The probability of remission declined by 49% for every suicide attempt made before the index manic episode. Mixed mania, multiple previous hospitalizations, and previous suicide attempts were significantly associated with current suicidality.Conclusions:Suicidality is linked with mixed manic states and may be a clinical marker for recurrent dysphoric mania. Multiple suicide attempts are associated with nonremission from mixed manic episodes. Am J Psychiatry 1998; 155: 1753-1755
Keeping healthy on a minimum wage
Authors: Christopher Deeming
Journal: BMJ (2005)

equivalent to paroxetine, 10 costs only 82p, compared with £1.62 for paroxetine.His case studies suggest that complementary and alternative programmes can lead to savings in direct costs, but these savings will be greatly diminished or abolished when set against the overall costs of providing these services.The provision of specific complementary and alternative interventions by members of existing primary healthcare teams might offer scope for cost savings in such settings.The report concludes that complementary and alternative therapies should be targeted at the "effectiveness gaps" of conventional health care, 11 particularly in managing chronic pain and mental disorders, and in palliative care.We think this is a useful concept but were perplexed by Smallwood including asthma, for which conventional treatment is generally effective and safe.Despite its limitations and the likelihood of bias in its conclusions, we believe that the Smallwood report fulfills a useful political function.It should promote more investment in research on the cost effectiveness of complementary and alternative treatments.Nevertheless, the report's principal recommendation-that NICE (the National Institute for Health and Clinical Excellence) carries out a full assessment of the cost effectiveness of these therapies-is ill advised.A more sensible recommendation to NICE would be that, in developing the scope of new guidelines on chronic conditions, the institute pays greater attention to reviewing complementary therapies.Therapists with particular expertise in complementary and alternative treatments for each specific condition should be invited to join guideline development groups.These groups can wrestle with the philosophical and methodological dilemmas over what study designs should be included in the evidence base of the guidelines.Uncertain evidence of effectiveness does not preclude a positive recommendation in a guideline, and original modelling of cost effectiveness can be part of guideline development. 12astly, those making decisions about integrated medicine in the NHS should consider each complementary or alternative therapy on its merits, using a broad range of appropriate scientific evidence including data on cost effectiveness.Such decision making, if done transparently, may change the public perception of scientific medicine for the better.
Nuffield Council opens consultation on use of personal biological and health data
Authors: M. Limb
Journal: BMJ (2013)

A major initiative has begun to find out what UK citizens think about their biological and health data being used by research, government, and commercial interests, potentially on a global scale.

The Nuffield Council of Bioethics said that its consultation, launched on 17 October,1 would give people a say on the many implications of widening access to “unprecedented” quantities of data.

It said that people’s views would inform a policy response to technological and scientific advances that have given many parties new opportunities to collect, use, analyse, and link up people’s personal health information.

The council has established a working group to examine ethical questions raised by …
Nuclear receptor PXR: discovery of a pharmaceutical anti-target
Authors: Steven A. Kliewer
Journal: Journal of Clinical Investigation (2015)

Transcriptional induction of the gene encoding cytochrome P450 3A oxygenase (CYP3A) causes a prominent class of dangerous drug-drug interactions wherein one drug accelerates the metabolism of another. In our 1998 JCI paper, we reported the cloning of the human nuclear receptor PXR and demonstrated that it mediates CYP3A induction. We determined that PXR is expressed in liver, acts through a DNA response element located in the CYP3A promoter, and is activated by a structurally diverse collection of drugs that induce CYP3A. Our findings revealed the molecular basis for the CYP3A induction class of drug-drug interactions and provided a high-throughput means for screening out drug candidates with this activity.
A CLINICAL AND BACTERIOLOGICAL INVESTIGATION OF PUERPERAL FEVER: IN THE ROTUNDA HOSPITAL, DUBLIN
Authors: G. Fitzgibbon, J. W. Bigger
Journal: BMJ (1925)

uponi the predisposing-and tlhe actual causes of pLuerperal sepsis as will lead to a much larger measure of prevention and to miiore effective treatment, and there can be little doubt tlha-t a vely real contribution to, that end will be reckoinetl aimlonig the many good results of this Congress.
Phosphatidylinositol-specific Phospholipase C in Fetal Membranes and Uterine Decidua
Authors: Gian Carlo Di Renzo, John M. Johnston, Takeshi Okazaki, Janice R. Okita, Paul C. MacDonald, John E. Bleasdale
Journal: Journal of Clinical Investigation (1981)

An assay procedure was developed in which phosphatidyl[2-3H]inositol was employed as substrate for the measurement of phosphatidylinositol-specific phospholipase C activity. Employing this assay, phosphatidylinositol-specific phospholipase C activity in human fetal membranes and uterine decidua was identified and characterized. The specific activity of this enzyme in amnion (4.4 μmol × mg−1 protein × h−1) was three times that in uterine decidua and more than five times that in chorion laeve. No difference was found between the specific activity of phosphatidylinositol-specific phospholipase C in placental amnion and that in reflected amnion. The products of phosphatidylinositol hydrolysis in short-term incubations were stoichiometric amounts of diacylglycerol and inositol-1,2-cyclic-phosphate plus inositol-1-phosphate. After longer periods of incubation, monoacylglycerol also was detected. Diacylglycerol lipase activity also was demonstrated in these tissues. More than 90% of phosphatidylinositol-specific phospholipase C activity of amnion tissue was recovered in the 105,000-g supernatant fraction, and optimal enzymatic activity in vitro was observed at pH 6.5-7.5 in the presence of Ca2+ (8 mM) and mercaptoethanol (4 mM). Phosphatidylinositol-specific phospholipase C activity was stimulated by fatty acids in low concentrations, but was inhibited by lysophosphatidylcholine and a variety of detergents. No effect of labor on the specific activity of phosphatidylinositol-specific phospholipase C in either fetal membranes or uterine decidua could be detected. The finding of an active phosphatidylinositol-specific phospholipase C activity in human fetal membranes and uterine decidua is complementary to our previous finding of a selective loss of arachidonic acid from phosphatidylinositol of human fetal membranes during labor. The action of phosphatidylinositol-specific phospholipase C, coupled to diacylglycerol lipase action, could provide a mechanism for the release of arachidonic acid for prostaglandin biosynthesis during parturition.
Points from Letters: Charges for Patients
Authors: S. Shubsachs
Journal: BMJ (1965)

African rural population (10 July, p. 111) will come as a shock to those who may have changed from moderate cigarette smoking to pipe smoking as a preventive measure.Contrasting the relative lung-cancer death rates for (1) smokers of up to 20 cigarettes a day and (2) pipe smokers in his survey and that of Hammond and Horn' in America gives the following results: Lung-cancer Lung-cancer Mortality Mortality Compared with Compared with that of that of the Non-smokers Total Average > $ > uS.> d_ U-U ~hU C4 0Hammond and Horn's study of white Americans aged 50- 69 (1952-5)' .. 793% 301% 149% 57%NODean's study of white South Africans aged 45-64 (1947-60) 186% 486% 43%/o 113%
The Contractile Structure of Cardiac and Skeletal Muscle
Authors: Charles E. Kossmann, H. E. HUXLEY
Journal: Circulation (1961)

Previous findings that have led to the `sliding-filament' model for striated muscle are reviewed, together with some recent observations on isolated filaments produced by a new procedure. The basic structure of the contractile apparatus in skeletal and in cardiac muscle appears to be identical. The relation between certain special features of cardiac muscle and its structure is discussed.
Columbus' Trip and Syphilis
Authors: Theodor Rosebury
Journal: JAMA (1977)

To the Editor.—  Dr Lopez repeats the old tale that although the place of origin is still argued, it is accepted by most that [syphilis] came from America and that it was taken to Europe by Columbus's sailors on their return from the first trip. In support, he cites three references, and in the next sentence, by implication, a fourth (De las Casas). Of the first three, Sudhoff1in fact provides important information to the contrary. Sudhoff, Hudson,2,3Holcomb,4and most recently Hackett,5have painstakingly reviewed this question and exculpated the American aborigines, with only ambiguous data on pre-Columbian bones in Lopez's favor, and a mass of evidence to the contrary, circumstantial and inconclusive to be sure, but such that no fair jury could convict.  Of course, irrefutable evidence on the point at issue may never be available; even some as yet undiscovered paleoimmunological method might
A Prospective Study of Nighttime Vital Sign Monitoring Frequency and Risk of Clinical Deterioration
Authors: Jordan C. Yoder, Trevor C. Yuen, Matthew M. Churpek, Vineet M. Arora, Dana P. Edelson
Journal: JAMA Internal Medicine (2013)

The routine practice of collecting vital signs every 4 hours in hospitalized ward patients has been perpetuated since as early as 1893, but there is little evidence to support this tradition1. Although vital signs can be indicative of impending clinical deterioration, routine nighttime vital sign monitoring adds to the already fragmented sleep of inpatients. Sleep disruptions are prevalent among ward patients and are associated several negative health outcomes, including elevated blood pressures and delirium2,3. Overnight vital sign checks not only are an especially bothersome disruptor but also can deplete crucial health care resources. Track and trigger systems, such as the Modified Early Warning Score (MEWS), have been used to identify high-risk patients for critical interventions4. The present study investigated whether the MEWS could identify low-risk-patients who might forgo overnight vital sign monitoring.
PERCUTANEOUS CORONARY INTERVENTION OF A NONINFARCT ARTERY IN SELECTED PATIENTS WITH ST-ELEVATION MYOCARDIAL INFARCTION MAINTAINS EXCELLENT CLINICAL OUTCOMES AND ACHIEVES SUBSTANTIAL COST SAVINGS COMPARED TO STAGED SECOND-VESSEL INTERVENTION
Authors: Lisa Schmitz, Tonga Nfor, Robert Ninneman, Paul Bernstein, Ramagopal Tumuluri, Jayant Khitha, Joaquin Solis, Yoseph Shalev, Anjan Gupta, Suhail Allaqaband, Tanvir Bajwa, Anthony DeFranco
Journal: Journal of the American College of Cardiology (2012)
Prednisolone vs. ciclosporin for severe adult eczema. An investigator-initiated double-blind placebo-controlled multicentre trial
Authors: J. Schmitt, K. Schäkel, R. Fölster-Holst, A. Bauer, R. Oertel, M. Augustin, W. Aberer, T. Luger, M. Meurer
Journal: British Journal of Dermatology (2009)

Background Patients with severe eczema frequently receive systemic glucocorticosteroids. The efficacy of prednisolone and other steroids, however, has never been evaluated appropriately. A meta‐analysis indicated that ciclosporin is the best evaluated systemic treatment for eczema. Objectives To investigate the comparative efficacy of prednisolone and ciclosporin for severe eczema. Methods In an investigator‐initiated double‐blind randomized multicentre trial, adults with severe eczema (objective SCORAD ≥ 40 and Dermatology Life Quality Index ≥ 10) were randomly allocated to receive prednisolone (initial dose 0·5–0·8 mg kg−1 daily) for 2 weeks followed by placebo for 4 weeks or ciclosporin (2·7–4·0 mg kg−1 daily) for 6 weeks and followed for another 12 weeks. Concomitant treatment included a moderately potent topical steroid, emollients, and continuation of antihistamines. Primary endpoint was the proportion of patients with stable remission, i.e. ≥ 50% SCORAD improvement under active treatment and no flare (≥ 75% of baseline SCORAD) during follow‐up. Sample size calculation indicated that 66 patients were needed to see clinically relevant differences between groups. Analysis was by intention‐to‐treat (ClinicalTrials.gov Identifier: NCT00445081). Results Because of unexpectedly high numbers of withdrawals due to significant exacerbations of eczema (n =15/38) an independent data monitoring and safety board proposed early study termination. Thirty‐eight patients were randomized and analysed. Stable remission was achieved in one of 21 patients receiving prednisolone compared with six of 17 patients treated with ciclosporin (P =0·031). Conclusions Ciclosporin is significantly more efficacious than prednisolone for severe adult eczema. Despite its frequent use in daily practice, prednisolone is not recommended to induce stable remission of eczema.
Columbia, Critical Care, Computers, and Consultants
Authors: John R. Clarke
Journal: JAMA (1982)

The spacecraft<i>Columbia</i>illustrates the human capacity for developing and solving complex problems. I understand Newton's laws, but my mind refuses to even enumerate the thousands of logistical, structural, and astronautical problems that had to be individually solved and integrated to make the<i>Columbia</i>lift off. People did solve those problems.<i>Columbia</i>flies. The critical care unit is a complexity I understand. I can appreciate subtleties in problems from medical to administrative to ethical, and their interactions. Daily, I make decisions that are potentially marked "right" or "wrong" by life or death. I am not always right, but I understand the pressures that impinge on and repercussions that result from a single decision. Presumably, my astronautical colleagues would be as paralyzed by their lack of knowledge in my field, as I am in theirs. Not only do I make decisions in the critical care unit, I explain the decisions and
Randomized comparison of 12 or 24 weeks of peginterferon α-2a and ribavirin in chronic hepatitis C virus genotype 2/3 infection
Authors: Martin Lagging, Nina Langeland, Court Pedersen, Martti Färkkilä, Mads Rauning Buhl, Kristine Mφrch, Amar P. Dhillon, Åsa Alsiö, Kristoffer Hellstrand, Johan Westin, Gunnar Norkrans
Journal: Hepatology (2008)

Previous trials investigating the efficacy of treatment durations shorter than the standard of 24 weeks for chronic hepatitis C virus (HCV) genotype 2/3 infections have yielded discordant results. The aims of this investigator-initiated phase III study were to compare the efficacy of 12 or 24 weeks of treatment and to identify patients suitable for short-term therapy. Three hundred eighty-two genotype 2/3–infected patients [intention-to-treat (ITT) population] at 31 centers in Denmark, Finland, Norway, and Sweden were randomized to 12 or 24 weeks of peginterferon α-2a (180 μg/week) plus ribavirin (800 mg/day). Twelve weeks of therapy was inferior to 24 weeks in the ITT population (sustained viral response [SVR] rates: 59% versus 78%, P &lt; 0.0001) and in the subgroups of patients infected with genotype 2 (56% versus 82%, P = 0.006) or 3 (58% versus 78%, P = 0.0015). These differences were observed regardless of the fibrosis stage. Age and HCV-RNA levels on days 7 and 29 were independent predictors of SVR. Short-term treatment was useful in patients &lt; 40 years old, especially if HCV-RNA was undetectable on day 29, and also in patients ≥ 40 years old, provided that HCV-RNA was below 1000 IU/mL on day 7 in addition to being undetectable on day 29. If neither of these two criteria were met for patients ≥ 40 years old, 24 weeks of therapy was superior ( P &lt; 0.0001). Conclusion: Peginterferon/ribavirin treatment for 12 weeks in HCV genotype 2/3 infection is overall inferior to 24 weeks of treatment but may be useful in some patients with a rapid initial clearance of virus.
Fungal Sinusitis and Marijuana-Reply
Authors: Walter Brummund
Journal: JAMA (1987)

In Reply.—  We considered marijuana smoking to be a possible source of exposure to the fungal antigen. However, because the marijuana smoking occurred several years prior to our patient's clinical presentation, we were unable to explore this possibility. Results of two previous studies from our group 1,2 regarding fungal exposure from marijuana cigarettes revealed the presence of a number of fungi and actinomycetes, including Aspergillus fumigatus, Aspergillus flavus, Aspergillus niger, Penicillium and Mucor species, Thermoactinomyces candidus, and Thermoactinomyces vulgaris . Although no Curvularia species were found in either of the two studies, we believe that recreational marijuana smoking could serve as a source for the development of fungal sinusitis.
A prospective, randomized trial of thromboatherectomy during intervention of thrombotic native coronary arteries and saphenous vein grafts: The X-TRACT trial
Authors: Gregg W. Stone, David A. Cox, Joseph D. Babb, Dean Nukta, Luc Bilodeau, Louis Cannon, Thomas D. Stuckey, James Hermiller, Eric Cohen, Reginald Low, Alexandra J. Lansky, Steven R. Bailey, Richard E. Kuntz
Journal: Journal of the American College of Cardiology (2003)
Primary amyloidosis and severe intrahepatic cholestatic jaundice.
Authors: R A Peters, G Koukoulis, A Gimson, B Portmann, D Westaby, R Williams
Journal: Gut (1994)

Liver involvement in systemic amyloidosis is frequent but is rarely of clinical importance. Five patients with severe cholestatic jaundice are described and an additional 20 from published reports are reviewed. The most frequent presenting symptoms were lethargy and abdominal pain, which were present for a median of 11 months before the onset of jaundice. Hepatomegaly, usually marked, was present in 92%, with ascites in 56% of the cases. The serum bilirubin concentration was noticeably high and the serum globulin low. Histology of the liver showed considerable perisinusoidal deposition with a slight predilection for the periportal area. Two patients presented with predominant centrilobular deposition. Congo red staining was not uniformly positive. A variety of treatment regimens was tried but median survival was only three months from the onset of jaundice.