tbuckley/cabot-search huggingface dataset:
Pentraxin‐3 in chronic heart failure: the CORONA and GISSI‐HF trials
Authors: Roberto Latini, Lars Gullestad, Serge Masson, Ståle Haugset Nymo, Thor Ueland, Ivan Cuccovillo, Mari Vårdal, Barbara Bottazzi, Alberto Mantovani, Donata Lucci, Nobuhito Masuda, Yukio Sudo, John Wikstrand, Gianni Tognoni, Pål Aukrust, Luigi Tavazzi
Journal: European Journal of Heart Failure (2012)
&lt;emph type="ital"&gt;CYP2C19&lt;/emph&gt; Genotype and Cardiovascular Events—Reply
Authors: Aroon D. Hingorani
Journal: JAMA (2012)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
The Normal Counterpart of IgD Myeloma Cells in Germinal Center Displays Extensively Mutated IgVH Gene, Cμ–Cδ Switch, and λ Light Chain Expression
Authors: Christophe Arpin, Odette de Bouteiller, Diane Razanajaona, Isabelle Fugier-Vivier, Francine Brière, Jacques Banchereau, Serge Lebecque, Yong-Jun Liu
Journal: The Journal of Experimental Medicine (1998)

Human myeloma are incurable hematologic cancers of immunoglobulin-secreting plasma cells in bone marrow. Although malignant plasma cells can be almost eradicated from the patient's bone marrow by chemotherapy, drug-resistant myeloma precursor cells persist in an apparently cryptic compartment. Controversy exists as to whether myeloma precursor cells are hematopoietic stem cells, pre–B cells, germinal center (GC) B cells, circulating memory cells, or plasma blasts. This situation reflects what has been a general problem in cancer research for years: how to compare a tumor with its normal counterpart. Although several studies have demonstrated somatically mutated immunoglobulin variable region genes in multiple myeloma, it is unclear if myeloma cells are derived from GCs or post-GC memory B cells. Immunoglobulin (Ig)D-secreting myeloma have two unique immunoglobulin features, including a biased λ light chain expression and a Cμ–Cδ isotype switch. Using surface markers, we have previously isolated a population of surface IgM−IgD+CD38+ GC B cells that carry the most impressive somatic mutation in their IgV genes. Here we show that this population of GC B cells displays the two molecular features of IgD-secreting myeloma cells: a biased λ light chain expression and a Cμ–Cδ isotype switch. The demonstration of these peculiar GC B cells to differentiate into IgD-secreting plasma cells but not memory B cells both in vivo and in vitro suggests that IgD-secreting plasma and myeloma cells are derived from GCs.
Messages to medical men
Authors: Percy Sharp
Journal: BMJ (2004)

Sir,—In reference to the above question I have been in the habit for some years past of trying to educate the public in my immediate neighbourhood, in the great importance of sending proper messages—especially in urgent cases. This I have tried to do by relating one or more of the following incidents in my ambulance lectures:

1.  A little girl called one morning with the message: “Please will you call and see Ma this morning.” …
Early Balloon Dilatation of the Pulmonary Valve in Infants With Tetralogy of Fallot
Authors: T. Sluysmans, B. Neven, J. Rubay, J. Lintermans, C. Ovaert, J. Mucumbitsi, P. Shango, M. Stijns, A. Vliers
Journal: Circulation (1995)

Balloon dilatation, an established treatment for pulmonary valve stenosis, remains a controversial procedure in tetralogy of Fallot.Balloon dilatation of the pulmonary valve was performed in 19 infants with tetralogy of Fallot. Its effects on the severity of cyanosis, the growth of the pulmonary valve and pulmonary arteries, and the need for transannular patching were evaluated. Clinical, echographic, angiographic, hemodynamic, and operative data were analyzed. The procedure was safe in all, without significant complications. After balloon dilatation, systemic oxygen saturation increased from a mean value of 79% to 90%. This increase proved to be short-lasting in 4 patients, who required surgery before the age of 6 months. Balloon dilatation increased pulmonary annulus size in each case, from a mean value of 4.9 to 6.9 mm (P < .001). This gain in size remained stable over time, with a mean Z score of -4.8 SD before dilatation, -3.1 SD immediately after the procedure, and -2.7 SD at preoperative catheterization (P < .001). Pulmonary artery dimensions remained unchanged immediately after balloon dilatation but increased at follow-up from a Z score mean value of -2.5 to -0.06 SD and from -2.2 to 0.04 SD for right and left pulmonary arteries, respectively (P < .001). At the time of corrective surgery, the pulmonary annulus was considered large enough to avoid a transannular patch in 69% of the infants. This represented a 30% to 40% reduction in the need for a transannular patch compared with the incidence of transannular patch expected before balloon dilatation.Pulmonary valve dilatation in infants with tetralogy of Fallot is a relatively safe procedure and appears to produce adequate palliation in most patients. It allowed the growth of the pulmonary annulus and of the pulmonary arteries, resulting in a mean gain of 2 SD for those structures.
Identification of programmed cell death in normal human skin tissues by using specific labelling of fragmented DNA
Authors: Y. TAMADA, H. TAKAMA, T. KITAMURA, K. YOKOCHI, Y. NITTA, T. IKEYA, Y. MATSUMOTO
Journal: British Journal of Dermatology (2006)

Programmed cell death (PCD) in normal human skin tissues was studied by using in situ specific labelling of fragmented DNA. This labelling method clearly stained the nuclei of Henle's layer in the bulb of the anagen hair follicle in serial sections, and the nuclei of the inner root sheath cuticle cells and Huxley's layer cells showed positive staining in the upper part of the hair follicles. This staining pattern was consistent with the sequence of keratinization in the three layers. The nuclei of differentiated cells located at the centre of the sebaceous glands, and those of the granular keratinocyte layer, were also stained. These findings suggest that PCD might play a key role in the terminal differentiation of the epidermis and epidermal appendages.
The triumph of NICE
Authors: Richard Smith
Journal: BMJ (2004)

The National Institute for Clinical Excellence (NICE) and the Commission for Health Improvement (CHI) were both introduced in the NHS plan of 1998. Six years on, CHI is dead but NICE is conquering the world. NICE worked but “nasty” (as CHI was initially known) failed—perhaps because it wasn't nasty enough. NICE may prove to be one of Britain's greatest cultural exports, along with Shakespeare, Newtonian physics, the Beatles, Harry Potter, and the Teletubbies.

Cynical about government and trained to be sceptical, the BMJ was cautious in its welcome to NICE (BMJ 1999;318: 823). We believed that a body was needed to lead on rationing …
WHO's avian influenza tsar takes Director-General post
Authors: Hannah Brown
Journal: The Lancet Infectious Diseases (2006)

Margaret Chan, WHO's former Special Representative of the Director General for Pandemic Influenza, will be the agency's next Director-General, it was revealed at the organisation's headquarters in Geneva on Nov 8. The decision of WHO's 34-member Executive Board to nominate Chan as their preferred candidate was confirmed by vote in a special 1-day World Health Assembly to be held at the UN building in Geneva, the Palais de Nations, on Nov 9.
Internalizing Behaviors in 4-Year-Old Children Exposed in Utero to Psychotropic Medications
Authors: Shaila Misri
Journal: American Journal of Psychiatry (2006)

Internalizing behaviors in children between 4 and 5 years of age who had been prenatally exposed to psychotropic medications were investigated. The authors had previously reported the effects of prenatal medication exposure in this same cohort when they were newborns and infants at 3 and 8 months of age.Parental/teacher reports and a clinical measure of mother and child interactions were used to assess levels of internalizing behaviors (e.g., depression, anxiety, withdrawal). Outcomes were compared between children with prenatal selective serotonin reuptake inhibitor (SSRI) exposure (N=22) and nonexposed children of healthy, nondepressed, nonmedicated mothers (N=14). Measures of maternal mood were obtained. Ordered logistic regressions, independent-sample t tests, and univariate ANOVAs were used to compare outcomes between groups. Pearson correlations were used to determine associations between maternal mood and child behaviors.Levels of internalizing behaviors did not differ significantly between children with prenatal psychotropic medication exposure and those not exposed. However, as symptoms of maternal anxiety and depression increased, so did reported internalizing behaviors in their children.Prenatal exposure to psychotropic medications was not associated with increased reports of internalizing behaviors at 4 years of age, whereas impaired maternal mood did have an identified impact on child behavior. Further study of complex associations between maternal psychiatric disorders, prenatal SSRI exposure, and childhood internalizing behaviors is required to understand if the child outcome is affected by the illness, medications, or a combination of both.
Influence of Nitroglycerin on Myocardial Metabolism and Hemodynamics during Angina Induced by Atrial Pacing
Authors: MIGUEL A. CHIONG, ROXROY O. WEST, JOHN O. PARKER
Journal: Circulation (1972)

Myocardial lactate extraction, arterial-coronary sinus difference (A-CS) of potassium (K + ), hemodynamics, and S-T segments were studied in 15 patients with coronary artery disease who developed angina during atrial pacing. The study consisted of the following periods: control (C 1 ), pacing (P 1 ), recovery (C 2 ), control after nitroglycerin (C GTN ), second pacing (P 2 ), and recovery. During C 1 , mean lactate extraction, S-T segments, and left ventricular end-diastolic pressure (LVEDP) were normal, and there was no myocardial K + loss. During P 1 the mean lactate production was –12.0%, mean K + loss –0.26 mEq/liter, and mean S-T segment depression 1.97 mm, while the average LVEDP remained unchanged, increasing when pacing was discontinued to a mean value of 23.3 mm Hg. These values returned to control levels by the time GTN was administered. After GTN there were significant decreases in mean cardiac index, LVEDP, brachial artery pressure, and left ventricular stroke work. During P 2 , eight subjects had no pain, five experienced less severe angina, mean lactate production and K + loss were abolished, S-T segments became less depressed (0.8 mm), and mean LVEDP decreased during pacing, rising only to 11.4 mm Hg when pacing was discontinued. Myocardial lactate production reverted to extraction in two patients and decreased in another two, whereas seven patients showed a decreased K + loss or uptake. It is concluded that GTN may prevent or reduce pacing-induced angina, as well as improve the electrocardiogram and hemodynamics, and in some patients decrease myocardial anaerobiosis.
Abstract P5-11-03: Deciphering the role of HER3-DJ-1 interaction in breast cancer
Authors: S Mukherjee, Z Huang, M Fa, P Dhupkar, K Mujoo, N Zhang, Z An
Journal: Cancer Research (2013)

Abstract Advanced breast cancer is notorious for its aggressive nature and poor prognosis. An ablated regulation in the EGFR family receptor signaling has been linked to the development of numerous tumor types, including breast cancer. HER3 is a unique member of the EGFR family that lacks intrinsic tyrosine kinase activity. However, HER3 can initiate signaling when dimerized with other family members such as HER2. HER3 overexpression is correlated with poor survival in breast cancer patients. HER3 also plays an important role in drug resistance mechanism such as in trastuzumab resistant breast cancer cell lines where it dimerize with EGFR to initiate signaling via the PI3K/Akt pathway. The identification of interaction partners of HER3's C-tail is critical to understand the signaling mechanism underpinning HER3's role in drug resistance and in progression of breast cancer. Our laboratory has identified a panel of novel HER3-interacting proteins by a combined immunoprecipitation and mass-spectrometry approach. One of the novel HER3 interacting proteins is DJ-1 which is a chaperone protein that plays an important role in the development of many cancers, including breast cancer. DJ-1 knockdown in high HER3 expressing breast cancer cell lines such as MCF-7 and MDA- MB-453 resulted in the reduction in HER3 levels as well as proteins downstream of the HER3 signaling pathway such as MAPK. We have also demonstrated that DJ-1 knockdown led to decrease in cancer cell proliferation. Studies are now in progress to determine the mechanism of regulation of HER3 by DJ-1 and the impact of DJ-1 KD in in vivo breast cancer xenograft models. These studies will help us to decipher key molecules which regulate HER3 mediated signaling and their role in breast cancer development and progression. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P5-11-03.
GPs' role and recognition:... and ignored
Authors: P. McCartney
Journal: BMJ (1993)

Smoking related to clinical diagnosisNo of controls No (o/o) of smokers No of No (%) of Age in same age in aged marked patients smokers range range controls Periductal mastitis 68 60 (88) 19-48 10 397 3955 (38O0)* Non-lactating 39 34 (87) 23-46 8 944 3441 (38-5)* Mammaryduct 32 30(94) 26-48 9 321 3504(37.6)*Duct ectasia 186 52 (28) 42-85 9 093 2722 (29 9) * p < 0 0001, XI test, comparing numbers of smokers and controls.view of Bundred and colleagues that periductal mastitis and duct ectasia are separate conditions with different clinical syndromes, different pathological features, and different aetiologies.Clinicians and pathologists should be aware of this and use appropriate terminology.
A CASE OF TETANUS TREATED BY INJECTION OF ANTITETANIC SERUM.
Authors: W. S. MORDEN
Journal: JAMA (1904)

<h3>History.</h3> —George F., aged 14, German, called me July 14. He said he awakened in the morning with a stiff neck and a general feeling of stiffness which he attributed to the jar of a mowing machine which he had ridden the day previous. I learned after considerable questioning that he had accidentally shot himself July 1 with a toy pistol, in the left hand half an inch from the base of the index and middle fingers. No attention was paid to the wound except to apply carbolic acid and do it up in an ordinary bandage. <h3>Examination.</h3> —The patient lay on his back with legs extended, head drawn back, face swollen, anxious expression. Temperature 101.5, pulse 96, respiration 20. All the muscles of trunk and limbs were rigid excepting those of the arms. The jaws could only be separated sufficiently to admit point of teaspoon
Nadolol is superior to isosorbide mononitrate for the prevention of the first variceal bleeding in cirrhotic patients with ascites
Authors: Gianmario Borroni, Francesco Salerno, Massimo Cazzaniga, Franco Bissoli, Elettra Lorenzano, Alessandra Maggi, Stefania Visentin, Anna Panzeri, Roberto de Franchis
Journal: Journal of Hepatology (2002)
Hepatitis C virus resistance to protease inhibitors
Authors: Philippe Halfon, Stephen Locarnini
Journal: Journal of Hepatology (2011)

Recent advances in molecular biology have led to the development of novel small molecules that target specific viral proteins of the hepatitis C virus (HCV) life cycle. These drugs, collectively termed directly acting antivirals (DAA) against HCV, include a range of non-structural (NS) 3/NS4A protease, NS5B polymerase, and NS5A inhibitors at various stages of clinical development. The rapid replication rate of HCV, along with the low fidelity of its polymerase, gives rise to generations of mutations throughout the viral genome resulting in remarkable sequence variation in the HCV population, known as a quasispecies. The efficacy of DAAs is limited by the presence of those mutations that give rise to amino-acid substitutions within the targeted protein, and that affect the viral sensitivity to these compounds. Thus, due to the high genetic variability of HCV, variants with reduced susceptibility to DAA can occur naturally even before treatment begins, but usually at low levels. Not surprisingly then, these changes are selected in patients either breaking through or not responding to potent DAA treatment. In vitro or in vivo, six major position mutations in the NS3 HCV protease (36, 54, 155, 156, 168, and 170) have now been reported associated with different levels of resistance. The amino acid composition at several of the drug resistance sites can vary between the HCV genotypes/subtypes, resulting in different consensus amino acids leading to a reduction in replicative fitness as well as reduced DAA sensitivity. Different amino acid diversity profiles for HCV genotypes/subtypes suggest differences in the position/type of immune escape and drug resistance mutations. Also, different pathways of resistance profiles based on the chemical scaffold (linear or macrocyclic) of the protease inhibitors have been described. This review first describes how resistance to a protease inhibitor can develop and then provides an overview of the mechanism of how particular mutations confer varying levels of resistance to protease inhibitor, which have been identified and characterized using both genotypic and phenotypic tools. Future potential therapeutic strategies to assist patients who do develop resistance to protease inhibitors are also outlined. The challenge developing new HCV protease inhibitors should take into consideration not only the antiviral potency of the drugs, the occurrence and importance of side effects, the frequency of oral administration, but also the resistance profiles of these agents.
1174 A NOVEL METHOD FOR NON-INVASIVE DIAGNOSIS OF HEPATITIS C VIRUS USING ELECTROMAGNETIC SIGNAL DETECTION: A MULTICENTER INTERNATIONAL STUDY
Authors: G. Shiha, W. Samir, A. Amien, H. Bader, T. Abdallah, A. Metwally, Z. Azam, P. Kar, S. Hamid, S. Sarin
Journal: Journal of Hepatology (2013)
Abstract LB-223: An open-label, exploratory phase II study of oral itraconazole for the treatment of basal cell carcinoma
Authors: Daniel Kim, James Kim, Katrina Spaunhurst, Javier Montoya, Kalyani Chandra, Rita Khodosh, Teresa Fu, Ervin H. Epstein, Montserrat Molgo, Philip Beachy, Jean Y. Tang
Journal: Cancer Research (2012)

Abstract Purpose: Itraconazole is an FDA-approved antifungal drug that has been recently shown to antagonize the Hedgehog (Hh) signaling pathway, a crucial driver of basal cell carcinoma (BCC) tumorigenesis. As oral itraconazole reduced BCC growth in mice, we assessed itraconazole's efficacy in treating human BCC tumors in an open-label, exploratory phase II study. Patients and Methods: Patients with at least one BCC tumor greater than 4 mm in diameter and with no co-morbidities were eligible to enroll. Patients were enrolled in 2 cohorts to receive oral itraconazole 200 mg twice-daily for one month (Cohort A) or 100 mg twice-daily for a longer duration (Cohort B). The primary endpoint was to determine changes in tumor size, proliferation (Ki67 levels), and a target gene of the Hh pathway (GLI1 mRNA). Results: Of the 29 patients that enrolled in the clinical trial, 19 patients were treated with itraconazole. Itraconazole caused 2 treatment-related adverse events (grade 2 fatigue and grade 4 CHF). Tumors treated with itraconazole showed a 23% reduction in clinical tumor area (95% CI: 17.2% to 28.1%), a 45% reduction in cell proliferation (P=0.04), and a 65% reduction in Hedgehog activity (P=0.03). Eight subjects with multiple tumors were assessed for clinical size changes: 4 subjects had partial response and 4 had stable disease. Tumors from control patients and patients previously treated with other Hedgehog inhibitors saw no significant changes in cell proliferation or Hedgehog activity. Conclusion: Itraconazole reduced BCC tumor size, tumor proliferation, and Hedgehog pathway activity in this exploratory study. Additional studies with larger numbers of patients are needed to validate these findings, however this proof-of-concept study demonstrates the possibility of repurposing FDA approved drugs for the treatment of cancers driven by the Hedgehog signaling pathway. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-223. doi:1538-7445.AM2012-LB-223
Interruption of the Ras/MEK/ERK signaling cascade enhances Chk1 inhibitor–induced DNA damage in vitro and in vivo in human multiple myeloma cells
Authors: Yun Dai, Shuang Chen, Xin-Yan Pei, Jorge A. Almenara, Lora B. Kramer, Charis A. Venditti, Paul Dent, Steven Grant
Journal: Blood (2008)
"Hypersensitivity hepatitis" associated with administration of cyclizine.
Authors: M C Kew, J Segel, A Zoutendyk
Journal: BMJ (1973)

fewer suffer from the former.The degree of coronary atheroma discovered in persons killed accidentally has been studied in many parts of the world, and the condition has been found to be equally widely distributed in the United States and United Kingdom.Yet, in contrast, the mortality from ischaemic heart disease is markedly different in com- parable populations, the U.S.A.F.: R.A.F.ratio approximating to 10: 1.2 The opinion expressed by Kannel3 that it is the presence of an effective collateral circulation which determines the clinical picture offers a reasonable explanation of the anomaly.Carboxyhaemoglobin is easily determined and is therefore a convenient marker of the products of com-bustion.It is possible that, because of this, carbon monoxide is being artificially promoted as a cause of disease.Workers in Los Angeles4 have attempted to relate atmospheric CO levels to an increased fatality rate from myocardial infarction; in fact, any relationship must be attributed to atmospheric pollution as a whole.In the same way, postmortem studies designed to show atherogenic properties of cigarette smoke5 fail to take into account the life style of heavy smokers.The case for an association between smoking and ischaemic heart disease seems proved beyond doubt.But rather than to attribute an atherogenic property to cigarettes in general and carbon monoxide in particular (Dr.Wald and his colleagues do not claimn this to be necessarily so), it might be more valid, and in keeping with the "collateral" theory, to suggest that the carboxyhaemoglobin results reported by them were more significantly reflecting the levels of nicotine, which is known to have a marked pharmacological effect on the cardiovascular system.-I am, etc.,