tbuckley/cabot-search huggingface dataset:
Varenicline for Smoking Cessation in Hospitalized Patients With Acute Coronary Syndrome
Authors: Mark J. Eisenberg, Sarah B. Windle, Nathalie Roy, Wayne Old, François R. Grondin, Iqbal Bata, Ayman Iskander, Claude Lauzon, Nalin Srivastava, Adam Clarke, Daniel Cassavar, Danielle Dion, Herbert Haught, Shamir R. Mehta, Jean-François Baril, Charles Lambert, Mina Madan, Beth L. Abramson, Payam Dehghani
Journal: Circulation (2015)

Background— Less than one-third of smokers hospitalized with an acute coronary syndrome (ACS) remain abstinent following discharge. We assessed whether varenicline, begun in-hospital, is efficacious for smoking cessation following ACS. Methods and Results— We conducted a multi-center, double-blind, randomized, placebo-controlled trial in which smokers hospitalized with an ACS were randomized to varenicline or placebo for 12 weeks. All patients received low-intensity counseling. The primary end point was point-prevalence smoking abstinence assessed at 24 weeks by 7-day recall and biochemical validation using expired carbon monoxide. A total of 302 patients were randomized (mean age 55±9 years; 75% male; 56% ST-segment elevation myocardial infarction; 38% non-ST-segment elevation myocardial infarction; 6% unstable angina). Patients smoked a mean of 21±11 cigarettes/d at the time of hospitalization and had been smoking for a mean of 36±12 years. At 24 weeks, patients randomized to varenicline had significantly higher rates of smoking abstinence and reduction than patients randomized to placebo. Point-prevalence abstinence rates were 47.3% in the varenicline group and 32.5% in the placebo group ( P =0.012; number needed to treat=6.8). Continuous abstinence rates were 35.8% and 25.8%, respectively ( P =0.081; number needed to treat=10.0), and rates of reduction ≥50% in daily cigarette consumption were 67.4% and 55.6%, respectively ( P =0.05; number needed to treat=8.5). Adverse event rates within 30 days of study drug discontinuation were similar between groups (serious adverse events: varenicline 11.9%, placebo 11.3%; major adverse cardiovascular events: varenicline 4.0%, placebo 4.6%). Conclusions— Varenicline, initiated in-hospital following ACS, is efficacious for smoking cessation. Future studies are needed to establish safety in these patients. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00794573.
Hemobilia and Hemophilia
Authors: Vicente Garrigues
Journal: Annals of Internal Medicine (1988)

Letters and Corrections15 August 1988Hemobilia and HemophiliaVicente Garrigues, MD, Adolfo del Val, MD, Julio Ponce, MD, Joaquin Berenguer, MDVicente Garrigues, MDSearch for more papers by this author, Adolfo del Val, MDSearch for more papers by this author, Julio Ponce, MDSearch for more papers by this author, Joaquin Berenguer, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-109-4-345_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the Editor:We report the case of a hemophiliac who presented with spontaneous hemobilia. A 45-year-old man was hospitalized for episodic upper abdominal pain. Severe hemophilia A had previously been diagnosed. Fifteen days before admission he had a self-limited episode of epigastric pain. Dark urine and light stools were noted, but hematemesis or melena was not present. The patient had jaundice and a temperature of 37.5° C. Abdominal organs were not enlarged. Hemoglobin was 9.3 g/dL; erythrocyte count, 3.13 X 1012/L; platelets, 178 X 109/L; leukocyte count, 5.5 X 109/L; total serum bilirubin, 4.8 mg/dL; direct bilirubin, 4.2 mg/mL;...References1. Sandblom P. Hemobilia. In: Schiff L, Schiff ER, eds. Diseases of the Liver. Philadelphia: J.B. Lippincott Co.; 1982; 1595-602. Google Scholar2. MittalSperoLewis RJJ. Patterns of gastrointestinal hemorrhage in hemophilia. Gastroenterology. 1985;88:515-22. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Gastroenterology Unit Hospital La Fe Valencia Spain PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByRare and Unusual Bleeding Manifestations in Congenital Bleeding DisordersHemobilia as the initial manifestation of cholangiocarcinoma in a hemophilia B patientSpontaneous intracholecystic bleeding in a patient with von Willebrand's disease 15 August 1988Volume 109, Issue 4Page: 345-345KeywordsAbdominal painBilirubinHemoglobinHemophiliaHemophilia APlateletsTemperatureUrine Issue Published: 15 August 1988 PDF DownloadLoading ...
Spectrum of Disease in Persons With Human Immunodeficiency Virus Infection in the United States
Authors: K M Farizo, J W Buehler, M E Chamberland, B M Whyte, E S Froelicher, S G Hopkins, C M Reed, E D Mokotoff, D L Cohn, S Troxler
Journal: JAMA (1992)

To describe the spectrum of disease in persons with human immunodeficiency virus (HIV) infection.Retrospective survey of medical records.More than 50 clinics, hospitals, and private medical practices in nine US cities.A total of 626 women and 7008 men 13 years of age or older with HIV infection who received medical care from January 1990 through March 1991 were consecutively enrolled.Any history of diseases in the 1987 case definition for the acquired immunodeficiency syndrome (AIDS), and during the 12-month period preceding enrollment (baseline period), the occurrence of other major diseases, hospitalizations, and results of CD4+ lymphocyte counts.Thirty-two percent of persons met the 1987 case definition for AIDS. The occurrence of an AIDS-indicator disease during the baseline period ranged from 3% (33/1011) to 46% (1254/2748) among persons with CD4+ lymphocyte counts of 0.50 x 10(9)/L or greater and fewer than 0.20 x 10(9)/L (greater than or equal to 500 and less than 200 CD4+ lymphocytes per microliter), respectively, and, at comparable CD4+ lymphocyte levels, was similar among women compared with men, and among persons who reported intravenous drug use compared with men who reported male-to-male sex. The frequency of one or more other major infectious diseases (eg, other pneumonias, bacterial sepsis, pulmonary tuberculosis) ranged from 6% to 16% among persons with CD4+ lymphocyte counts of 0.50 x 10(9)/L or greater and fewer than 0.20 x 10(9)/L, respectively; these illnesses were also associated with a history of intravenous drug use. Among persons who did not meet the 1987 AIDS case definition, 30% of those with an available CD4+ lymphocyte count had fewer CD4+ cells than 0.20 x 10(9)/L, 8% had one or more major infectious diseases, and 14% had one or more hospital admissions.For every person with AIDS at these sites, two additional persons with HIV infection were receiving medical care, many of whom had severe immunosuppression and a broad spectrum of serious HIV-related disease.
GP commissioners not spending enough on mental health, claims Labour
Authors: A. O'Dowd
Journal: BMJ (2014)

The Labour Party has criticised commissioning GPs in England for underfunding mental health services in their areas. Representatives of commissioning groups, however, have challenged the assertion, saying that many of the groups have made mental health a priority and are trying to ensure it has equal consideration with physical health needs.

Labour’s shadow public health minister, Luciana Berger, released figures on 25 July received from 142 of England’s 211 clinical commissioning groups (a 67% response rate) after a freedom of information request. The figures show that commissioning groups spent an average of 10% of their annual budget on mental health services in 2013-14, despite research showing it accounts …
Enhancement of Cancer Vaccine Therapy by Systemic Delivery of a Tumor-Targeting<i>Salmonella-</i>Based STAT3 shRNA Suppresses the Growth of Established Melanoma Tumors
Authors: Edwin R. Manuel, Céline A. Blache, Rebecca Paquette, Teodora I. Kaltcheva, Hidenobu Ishizaki, Joshua D.I. Ellenhorn, Michael Hensel, Leonid Metelitsa, Don J. Diamond
Journal: Cancer Research (2011)

Abstract Cancer vaccine therapies have only achieved limited success when focusing on effector immunity with the goal of eliciting robust tumor-specific T-cell responses. More recently, there is an emerging understanding that effective immunity can only be achieved by coordinate disruption of tumor-derived immunosuppression. Toward that goal, we have developed a potent Salmonella-based vaccine expressing codon-optimized survivin (CO-SVN), referred to as 3342Max. When used alone as a therapeutic vaccine, 3342Max can attenuate growth of aggressive murine melanomas overexpressing SVN. However, under more immunosuppressive conditions, such as those associated with larger tumor volumes, we found that the vaccine was ineffective. Vaccine efficacy could be rescued if tumor-bearing mice were treated initially with Salmonella encoding a short hairpin RNA (shRNA) targeting the tolerogenic molecule STAT3 (YS1646-shSTAT3). In vaccinated mice, silencing STAT3 increased the proliferation and granzyme B levels of intratumoral CD4+ and CD8+ T cells. The combined strategy also increased apoptosis in tumors of treated mice, enhancing tumor-specific killing of tumor targets. Interestingly, mice treated with YS1646-shSTAT3 or 3342Max alone were similarly unsuccessful in rejecting established tumors, whereas the combined regimen was highly potent. Our findings establish that a combined strategy of silencing immunosuppressive molecules followed by vaccination can act synergistically to attenuate tumor growth, and they offer a novel translational direction to improve tumor immunotherapy. Cancer Res; 71(12); 4183–91. ©2011 AACR.
Carbonic Anhydrase II Is a Tumor Vessel Endothelium–Associated Antigen Targeted by Dendritic Cell Therapy
Authors: Kenta Yoshiura, Takashi Nakaoka, Toshihide Nishishita, Katsuaki Sato, Akifumi Yamamoto, Shinji Shimada, Toshiaki Saida, Yutaka Kawakami, Tsuneo A. Takahashi, Hiroyuki Fukuda, Shinobu Imajoh-Ohmi, Naoki Oyaizu, Naohide Yamashita
Journal: Clinical Cancer Research (2005)

Abstract Tumor-associated antigens are promising candidates as target molecules for immunotherapy and a wide variety of tumor-associated antigens have been discovered through the presence of serum antibodies in cancer patients. We previously conducted dendritic cell therapy on 10 malignant melanoma patients and shrinkage or disappearance of metastatic tumors with massive necrosis occurred in two patients. In this study, we found a 29-kDa protein against which antibody was elicited by dendritic cell therapy in one of the two patients. Matrix-assisted laser desorption ionization-time of flight/mass spectrometry analysis of the protein isolated by two-dimensional electrophoresis combined with Western blots revealed that the 29-kDa protein was carbonic anhydrase II (CA-II). Immunohistochemistry of the tumors and normal tissues showed that CA-II was expressed in the tumor vessel but not in normal vessel endothelium. CA-II expression in tumor endothelium was observed as well in other cancers including esophageal, renal, and lung cancers. In an in vitro angiogenesis model, CA-II expression of normal human vein endothelial cells was significantly up-regulated when cells were cultured in the acidic and hypoxic conditions indicative of a tumor environment. These findings suggest that CA-II is a tumor vessel endothelium–associated antigen in melanoma and other cancers, and elicitation of serum anti–CA-II antibody by dendritic cell therapy may be associated with good clinical outcome including tumor reduction.
Submitting a manuscript
Authors: P. Quanjer
Journal: European Respiratory Journal (2010)

To the Editors: 

I feel a little stupid. Recently, I wanted to submit a manuscript to the European Respiratory Journal ( ERJ ). I went to the ERJ website but, rather bafflingly, did not seem to be able to find a reference as to how one could submit. After Googling I found http://mc.manuscriptcentral.com/erj. But there the system immediately defeated me. I had to sign in with a name and password. Not being aware of having the required login details, I tried the Help button by providing my e-mail address, and then enjoyed the bliss of eternal silence. In all fairness, a message actually arrived after about 30 minutes, but I had given up all hope before that time.

Whilst I was waiting, I noticed that there was a facility to register, so that is what I did. But I was …
Validation of an asthma quality of life diary in a clinical trial.
Authors: M E Hyland, G R Crocker
Journal: Thorax (1995)

BACKGROUND--Quality of life (QOL) is commonly measured in asthma clinical trials by a questionnaire given before and after treatment. A structured asthma QOL daily diary provides more restricted information but on a daily basis. The validity and use of such a QOL diary was examined in a clinical trial in which two asthma treatments were compared. METHODS--The effects of low dose inhaled steroid (400 micrograms beclomethasone dipropionate, BDP) combined with the long acting beta 2 agonist salmeterol (100 micrograms) (n = 220) was compared with high dose inhaled steroid (1000 micrograms BDP) (n = 206) in asthmatic outpatients in a double blind, parallel group study. Outcome measures consisted of a combined diary for peak expiratory flow (PEF) rate, symptoms, and problems, and an asthma-specific QOL questionnaire, the Living with Asthma Questionnaire. RESULTS--The QOL diary correlated with the QOL questionnaire for both cross sectional and longitudinal assessments. Cross sectional correlations with PEF were higher for the QOL questionnaire than the QOL diary, but longitudinal correlations with PEF were higher for the diary than the questionnaire. Treatment with low dose steroid/salmeterol compared with high dose steroid produced better lung function, better QOL as measured by diary, and reduced night time wakenings, but treatment differences were not obtained with the QOL questionnaire nor for daytime symptoms. Diary assessed QOL was a better predictor of low PEF than diary assessed symptoms. Compliance with diary completion was good but there were floor or ceiling effects in the QOL diary records of about 25% of patients. CONCLUSIONS--Structured QOL diaries are valid instruments that appear to be more responsive to longitudinal change in clinical trials than a QOL questionnaire, but QOL questionnaires provide a more sensitive cross sectional measure of disease severity. Floor and ceiling effects are found in some patients9 QOL diaries which limit their usefulness. QOL diary problem events occur during the troughs of a peak flow graph, while symptoms are more widely distributed with respect to peak flow.
Src Homology 2–containing 5-Inositol Phosphatase (SHIP) Suppresses an Early Stage of Lymphoid Cell Development through Elevated Interleukin-6 Production by Myeloid Cells in Bone Marrow
Authors: Koji Nakamura, Taku Kouro, Paul W. Kincade, Alexander Malykhin, Kazuhiko Maeda, K. Mark Coggeshall
Journal: The Journal of Experimental Medicine (2004)

The Src homology (SH)2–containing inositol 5-phosphatase (SHIP) negatively regulates a variety of immune responses through inhibitory immune receptors. In SHIP−/− animals, we found that the number of early lymphoid progenitors in the bone marrow was significantly reduced and accompanied by expansion of myeloid cells. We exploited an in vitro system using hematopoietic progenitors that reproduced the in vivo phenotype of SHIP−/− mice. Lineage-negative marrow (Lin−) cells isolated from wild-type mice failed to differentiate into B cells when cocultured with those of SHIP−/− mice. Furthermore, culture supernatants of SHIP−/− Lin− cells suppressed the B lineage expansion of wild-type lineage-negative cells, suggesting the presence of a suppressive cytokine. SHIP−/− Lin− cells contained more IL-6 transcripts than wild-type Lin− cells, and neutralizing anti–IL-6 antibody rescued the B lineage expansion suppressed by the supernatants of SHIP−/− Lin− cells. Finally, we found that addition of recombinant IL-6 to cultures of wild-type Lin− bone marrow cells reproduced the phenotype of SHIP−/− bone marrow cultures: suppression of B cell development and expansion of myeloid cells. The results identify IL-6 as an important regulatory cytokine that can suppress B lineage differentiation and drive excessive myeloid development in bone marrow.
Venocclusive Disease of the Liver after Bone Marrow Transplantation: Diagnosis, Incidence, and Predisposing Factors
Authors: George B. Mcdonald, Pankaj Sharma, David E. Matthews, Howard M. Shulman, Donnall E. Thomas
Journal: Hepatology (1984)

Venocclusive disease (VOD) of the liver, a fibrous obliteration of small hepatic venules, can be caused by chemoradiation therapy. We reviewed 255 consecutive patients undergoing bone marrow transplantation for malignancy during 1978 to 1980 in order to determine the incidence of VOD and the predisposing factors. Fifty-three of 255 patients met our criteria for VOD, for an incidence of 21%. Multivariate analysis showed that the most significant risk factors for VOD were age over 15, an underlying malignancy other than acute lymphocytic leukemia and hepatitis prior to transplantation. Patients with hepatitis had a 3. 4-fold risk of developing VOD, as compared to patients with normal SGOT values (p = 0.0004). Hepatitis in this setting is probably of non-A, non-B viral etiology and represents a relative contraindication to marrow transplantation because of enhanced toxicity from conditioning chemoradiotherapy.
Fetal Loss Associated With Excess Thyroid Hormone Exposure
Authors: João Anselmo
Journal: JAMA (2004)

ContextMaternal hypothyroidism and hyperthyroidism have deleterious effects on the outcome of pregnancy. While the effects of thyroid hormone (TH) deprivation on the fetus, independently from that on the mother, can be studied in infants with congenital hypothyroidism, this is not the case in those with fetal thyrotoxicosis.ObjectiveTo study the effects of TH excess on fetuses carried by mothers with resistance to TH (RTH) who are euthyroid despite high TH levels but who may carry normal fetuses that are exposed to high maternal hormone levels.Design, Setting, and ParticipantsRetrospective study of 167 members of an Azorean family with RTH. Affected individuals had the RTH phenotype (high serum concentration of free thyroxine and triiodothyronine without suppressed thyrotropin) confirmed by genotyping to identify the Arg243→Gln mutation in the TH receptor β gene.Main Outcome MeasuresPregnancy outcome of affected mothers vs that of unaffected mothers carrying fetuses conceived by affected fathers, as well as that of unaffected first-degree relatives and outcomes from the general island population. Comparison of birth weights and blood concentrations of thyrotropin (TSH) obtained during routine neonatal screening of infants born to these 3 groups.ResultsThirty-six couples with complete information belonged to 1 of 3 groups: affected mothers (n = 9), affected fathers (n = 9), and unaffected relatives (n = 18). Mean miscarriage rates were 22.9%, 2.0%, and 4.4%, respectively (χ2 = 8.66, P = .01). Affected mothers had an increased rate of miscarriage (z = 3.10, P = .002, by Wilcoxon rank-sum test). They had marginally higher than expected numbers of affected offspring, ie, 20 affected and 11 unaffected children (P = .07), while affected fathers had 15 affected and 12 unaffected children (P = .35). Unaffected infants born to affected mothers were significantly smaller than affected infants, having a mean SD score for gestational age of –1.79 (SD, 0.86) vs −0.06 (SD, 1.11) to –0.22 (SD, 0.70) for all other groups (P<.001). Only unaffected infants born to affected mothers had undetectable blood levels of TSH.ConclusionThere was a higher rate of miscarriage in mothers affected by RTH that may have involved predominantly unaffected fetuses. The lower birth weight and suppressed levels of TSH in unaffected infants born to affected mothers indicates that the high maternal TH levels produce fetal thyrotoxicosis. These data indicate a direct toxic effect of TH excess on the fetus.
Surgical wound infection as a performance indicator: agreement of common definitions of wound infection in 4773 patients
Authors: A P R Wilson, C Gibbons, B C Reeves, B Hodgson, M Liu, D Plummer, Z H Krukowski, J Bruce, J Wilson, A Pearson
Journal: BMJ (2004)

<h3>Abstract</h3> <b>Objective</b> To assess the level of agreement between common definitions of wound infection that might be used as performance indicators. <b>Design</b> Prospective observational study. <b>Setting</b> London teaching hospital group receiving emergency cases as well as tertiary referrals. <b>Participants</b> 4773 surgical patients staying in hospital at least two nights. <b>Main outcome measures</b> Numbers of wound infections based on purulent discharge alone, on the Centers for Disease Control (CDC) definition of wound infection, on the nosocomial infection national surveillance scheme (NINSS) version of the CDC definition, and on the ASEPSIS scoring method. <b>Results</b> 5804 surgical wounds were assessed during 5028 separate hospital admissions. The mean percentage of wounds classified as infected differed substantially with different definitions: 19.2% with the CDC definition (95% confidence interval 18.1% to 20.4%), 14.6% (13.6% to 15.6%) with the NINSS version, 12.3% (11.4% to 13.2%) with pus alone, and 6.8% (6.1% to 7.5%) with an ASEPSIS score &gt; 20. The agreement between definitions with respect to individual wounds was poor. Wounds with pus were automatically defined as infected with the CDC, NINSS, and pus alone definitions, but only 39% (283/714) of these had ASEPSIS scores &gt; 20. <b>Conclusions</b> Small changes made to the CDC definition or even in its interpretation, as with the NINSS version, caused major variation in estimated percentage of wound infection. Substantial numbers of wounds were differently classified across the grades of infection. A single definition used consistently can show changes in percentage wound infection over time at a single centre, but differences in interpretation prevent comparison between different centres.
Body Water Homeostasis
Authors: Robert W Schrier
Journal: Journal of the American Society of Nephrology (2006)

The discovery of the aquaporin-1 (AQP1) water channel by Agre and colleagues ([1][1],[2][2]), which led to the Nobel Prize in 2003, has revolutionized the understanding of body fluid water regulation by the kidney. Moreover, the identification of other water channels in the kidney, namely AQP2, 3,