tbuckley/cabot-search huggingface dataset:
The prognostic value of elevated levels of troponin I (Tn I) and heart-type fatty acid binding protein (H-FABP) in hospitalized COPD patients with acute respiratory failure (ARF)
Authors: Gulsara Baimakanova, Sergey Avdeev, Alexander Chuchalin
Journal: European Respiratory Journal (2012)

Aim: To evaluate the diagnostic and prognostic value of heart injury biomarkers (H-FABP and Tn I) in COPD patients with ARF.  Methods: We enrolled 80 hospitalized patients with COPD (65,6±18,9 years, PaO2 53.8±7.2 mm Hg). All patients underwent a complex diagnostic investigation including chest X-ray, blood gases, echocardiography, measurement of serum Tn I, H-FABP, BNP-fragment.  Results: The main causes of ARF were bacterial infection (BI)-43,7%, pneumonia-32,5%, acute decompensation of chronic heart failure (ADCHF)-12,5% and acute myocardial infarction (AMI)-11,3%. The H-FABP levels >1600 pg/mL were in 92.5% of all cases. Patients with AMI had the higher levels of H-FABP than patients with BI (9948,2 [4166,7-25000] vs 3720,0 [2620,1-5553,3] pg/mL, p 0,5 ng/mL) in 21,3% of all cases without significant differences between groups. BNP-fragment levels were higher in patients with pneumonia, ADCHF, AMI than in patients with BI (967,7 [453,7-2916,6], 2458,1[960,5-4869,2], 1939,6[982,2-2361,1] vs 463,7[306,8-1013,2] fmol/mL, p 0,5 ng/mL than in patients with Tn I   Conclusion: In COPD patients with ARF the serum levels of Tn I and H-FABP were significantly elevated without documented acute coronary syndrome and were the strong predictors for all-causes hospital mortality.
Living with severe chronic obstructive pulmonary disease (COPD): The male carer's story
Authors: Terry Robinson, Giles Fitch
Journal: European Respiratory Journal (2011)

Introduction and objectives:  The aim of this qualitative study was to gain a better knowledge and understanding of the male caring role in COPD, and to explore the ways in which individual carers live with COPD patients.   Methods:  A prospective unstructured audiotaped interview using a phenomenological approach was used to collect data from ten men (mean age 70.1 years) living with wives or partners who had severe COPD.   Results:  Recurrent themes emerged. Most participants reported lack of support and social isolation as they lacked the network of friends and family around them that women appear to have. Previously enjoyed activities such as holidays and sexual relationships were no longer possible for many, leading to increased stress and resentment. Hospital admissions led to increased work load and even less time for the men, and many described how the future filled them with fear, especially if their partner deteriorated further, or if their own health deteriorated. Surprisingly six men did not perceive themselves as carers, preferring the word “partner” to carer. As they did not see themselves as carers they did not think they were entitled to or asked for help. Five men felt that caring did not come naturally to men, and felt women were better suited to the role as they had historically raised children and run the family home.   Conclusion:  Severe COPD impacts on all aspects of male carers9 lives. The specific needs of male carers should be considered when designing and delivering services to this patient group.
Notice of Retraction and Replacement. Lopes et al. Gamma ventral capsulotomy for obsessive-compulsive disorder: a randomized clinical trial.<i>JAMA Psychiatry</i>. 2014;71(9):1066-1076
Authors: Antonio C. Lopes, Benjamin D. Greenberg, Carlos A. B. Pereira, Georg Norén, Euripedes C. Miguel
Journal: JAMA Psychiatry (2015)

In Reply On behalf of our coauthors, we are grateful to Dr Baethge for his detailed reading of our study.He is correct that for the primary outcome, we inadvertently misclassified a patient (ATa3) as a responder when indeed that patient was a nonresponder.When preparing the table, we inadvertently included in our computation of treatment response a Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) score of 36 (the patient's first measure) instead of 30 (the second measure).We defined the baseline Y-BOCS score for this study as the last value obtained before surgery.At that point, all patients knew they would receive the procedure.Thus, instead of 3 of 8 patients responding in the treatment group at 12 months, 2 of 8 responded compared with 0 of 8 in the control group.Because of this error, the analysis has been redone and we have requested that JAMA Psychiatry retract and replace the original article.In the corrected article, 1 corrections have been made to the Abstract; Results, Discussion, and Conclusions sections of the text; Tables 2 and3; Figure 2; and eFigure 3 and eTables 5, 6, and 7 in the Supplement.The article now concludes, "In this preliminary trial, patients with intractable OCD [obsessivecompulsive disorder] who underwent GVC [gamma ventral capsulotomy] may have benefitted more than those who un-derwent sham surgery although the difference did not reach statistical significance.Additional research is necessary to determine if GVC is better than deep-brain stimulation."We regret the errors caused by this misclassification as well as the confusion it caused for JAMA Psychiatry, readers, and potentially patients.
Azathioprine therapy selectively ablates human Vδ2+ T cells in Crohn’s disease
Authors: Neil E. McCarthy, Charlotte R. Hedin, Theodore J. Sanders, Protima Amon, Inva Hoti, Ibrahim Ayada, Vidya Baji, Edward M. Giles, Martha Wildemann, Zora Bashir, Kevin Whelan, Ian Sanderson, James O. Lindsay, Andrew J. Stagg
Journal: Journal of Clinical Investigation (2015)

Tumor-derived and bacterial phosphoantigens are recognized by unconventional lymphocytes that express a Vγ9Vδ2 T cell receptor (Vδ2 T cells) and mediate host protection against microbial infections and malignancies. Vδ2 T cells are absent in rodents but readily populate the human intestine, where their function is largely unknown. Here, we assessed Vδ2 T cell phenotype and function by flow cytometry in blood and intestinal tissue from Crohn's disease patients (CD patients) and healthy controls. Blood from CD patients included an increased percentage of gut-tropic integrin β7-expressing Vδ2 T cells, while "Th1-committed" CD27-expressing Vδ2 T cells were selectively depleted. A corresponding population of CD27+ Vδ2 T cells was present in mucosal biopsies from CD patients and produced elevated levels of TNFα compared with controls. In colonic mucosa from CD patients, Vδ2 T cell production of TNFα was reduced by pharmacological blockade of retinoic acid receptor-α (RARα) signaling, indicating that dietary vitamin metabolites can influence Vδ2 T cell function in inflamed intestine. Vδ2 T cells were ablated in blood and tissue from CD patients receiving azathioprine (AZA) therapy, and posttreatment Vδ2 T cell recovery correlated with time since drug withdrawal and inversely correlated with patient age. These results indicate that human Vδ2 T cells exert proinflammatory effects in CD that are modified by dietary vitamin metabolites and ablated by AZA therapy, which may help resolve intestinal inflammation but could increase malignancy risk by impairing systemic tumor surveillance.
Genotypic characterization of phenotypically defined triple-negative breast cancer
Authors: J. A. Sparano, L. J. Goldestin, B. H. Childs, S. Shak, S. Badve, F. L. Baehner, N. E. Davidson, G. W. Sledge, R. Gray
Journal: Journal of Clinical Oncology (2009)

500 Background: Triple negative breast cancer (TNBC) is associated with a higher risk of recurrence and earlier recurrences than other breast cancer phenotypes. We evaluated the genotypic features of TNBC compared with hormone receptor (HR)-positive disease, and also evaluated genotypic features associated with recurrence. Methods: RNA extracted from tumor samples obtained from 764 patients with stage I-III breast cancer was analyzed by RT-PCR for 371 genes. All patients received adjuvant chemotherapy (plus hormonal therapy in HR-positive disease) in trial E2197; HR and HER2 expression were evaluated by immunohistochemistry (IHC) in a central lab (J Clin Oncol 26:2473–2481). An unsupervised clustering analysis was performed in all samples (N=764). Cox proportional hazard models were used to identify differences in gene expression in TNBC versus HR-positive disease, and with recurrence in phenotypically defined (by IHC) TNBC (N=246) and HR-positive (N=465) disease. Results: Unsupervised analysis revealed two major clusters that differed with regard to HR expression by IHC. Supervised analysis comparing the TNBC vs. HR-positive phenotypes revealed 269 genes (73%) with significantly different expression (p&lt;0.0001). The top 10% of genes exhibiting higher expression the TN group included genes associated with nucleosome assembly (CENPA), kinase activity (TTK), cell division (KIFC2), proliferation (BUB1), intracellular signaling (DEPDC1), DNA repair (CHK1), anti-apoptosis (GSTP1), and transcriptional regulation (MYBL2). There was increased expression of genes for which inhibitors are currently being evaluated, including AURKB and CHK1 in TNBC, and IGF1R and RhoC in HR-positive disease. Although GRB7 expression was significantly lower in the TN group, increased expression of GRB7 was the only gene in the TNBC group (but not the HR-positive group) associated with increased recurrence (p=0.04), and did not correlate with nodal status, tumor size, or grade. Conclusions: We genotypically characterized breast cancers that have also undergone rigorous phenotypic characterization.. There were significant differences in gene expression between the TN and HR-positive groups, including genes for which targeted agents are currently being evaluated in the clinic. [Table: see text]
Predictive CT-parameters for detection with and diagnostic accuracy of EBUS-guided biopsy of suspected lung lesions
Authors: Canan Guvenc, Walter De Wever, Federica Zanca, Ann Carbonez, J. Yserbyt, D. Testelmans, Christophe Dooms
Journal: European Respiratory Journal (2014)

PURPOSE: 

To analyze predictive CT-parameters for lesion detection with Endobronchial Ultrasonography(EBUS) and for diagnostic accuracy of EBUS-guided biopsy of suspected lung lesions.

MATERIALS AND METHODS: 

From January 2011 to December 2013, retrospectively, CT images of 437 patients (287 males and 150 females; mean age, 67 years; range age, 5-97) with suspect lung lesion, who underwent EBUS-guided biopsy, were reviewed. Images were evaluated on presence of air-bronchogram, lesion size, distance between lesion and secondary carina, tertiary carina and pleura. The predictive values of these parameters on the detection and on diagnostic accuracy were evaluated using logistic regression analysis.

RESULTS: 

The predictive values of the different CT-parameterson detection of a lung lesion with EBUS and on diagnostic accuracy of EBUS-guided biopsy are mentioned in table 1.

View this table:

Table 1





CONCLUSION: 

Predictive CT-parameters with a significant influence on lung lesion detection with EBUS are: longest axial and coronal lesion diameter and distance between lesion and secondary or tertiary carina. The longest axial diameter is a predictive parameter for the accuracy of EBUS-guided biopsy.
Phase I Study of Liposomal Vincristine
Authors: K. A. Gelmon, A. Tolcher, A. R. Diab, M. B. Bally, L. Embree, N. Hudon, C. Dedhar, D. Ayers, A. Eisen, B. Melosky, C. Burge, P. Logan, L. D. Mayer
Journal: Journal of Clinical Oncology (1999)

PURPOSE: A phase I study of vincristine encapsulated inside 120-nm-diameter distearoylphosphatidylcholine-cholesterol liposomes was performed. The primary objectives were to determine the maximum-tolerated dose (MTD), recommended phase II dose, toxicity, and pharmacokinetics of liposomal vincristine (ONCO-TCS). PATIENTS AND METHODS: Twenty-five patients with histologically confirmed malignancies were enrolled and assessable. Vincristine doses were increased from 0.5 mg/m 2 to 1.0, 1.5, 2.0, 2.4, and 2.8 mg/m 2 with cohorts of three or more patients per dose level. A total of 64 courses of ONCO-TCS were administered intravenously once every 3 weeks. The pharmacokinetics of total vincristine content in plasma were determined using a high-performance liquid chromatography method. RESULTS: Patients were treated with vincristine doses up to 2.8 mg/m 2 ; however, 2.4 mg/m 2 was defined as the MTD and 2.0 mg/m 2 as the phase II recommended dose. Pain and obstipation were the dose-limiting toxicites. Other toxicities were fever, rigors, fatigue, myalgias, and peripheral neuropathy. Hematologic toxicity was mild. All patients who were treated with doses above 1.5 mg/m 2 received in excess of 2.0 mg of vincristine, with doses as high as 6.2 mg. One partial response was seen in a patient with pancreatic cancer. Tumor response not meeting partial response criteria was seen in two other patients. Pharmacokinetic studies revealed significantly elevated concentrations of total vincristine, but parameters varied and were not directly correlated with toxicity or response. CONCLUSION: The ability to administer elevated doses of vincristine, as well as indications of efficacy, suggests that ONCO-TCS warrants further clinical investigation in a phase II setting.
Demographics, family history, premorbid functioning, developmental characteristics, and course of patients with deteriorated affective disorder
Authors: C Vocisano, D N Klein, R S Keefe, E R Dienst, M M Kincaid
Journal: American Journal of Psychiatry (1996)

This exploratory study examined the characteristics of a group of unusual and previously undescribed patients with major affective disorder who not only had been continuously symptomatic for prolonged periods of time but were also so functionally impaired that they required years of continuous care in psychiatric facilities or by family members.Twenty-seven inpatients with major mood disorders and 29 inpatients with schizophrenia were recruited from a large state hospital; 27 outpatients with major mood disorders were recruited from an affiliated outpatient facility. The research battery included the Structured Clinical Interview for DSM-III-R--Patient Version, the Premorbid Adjustment Scale, and a semistructured interview designed to assess demographic, family history, developmental, and course information.Inpatients with deteriorated affective disorder differed from outpatients with nondeteriorated affective disorder along several important dimensions, including family history of mental illness, birth-related problems, physical disorders in infancy, premorbid functioning, presence of mixed episodes and rapid cycling, and medication non-compliance between hospitalizations. Inpatients with deteriorated affective disorder differed from inpatients with schizophrenia on the Premorbid Adjustment Scale. Patients with bipolar affective disorder differed from those with unipolar disorder on many of the variables associated with deterioration of functioning.Birth-related problems, physical disorders in infancy, and poor premorbid adjustment in childhood and adolescence appear to play an important role in deterioration of functioning among patients with unipolar depression. Disruption in treatment because of medication noncompliance and the appearance of mixed episodes and rapid cycling are associated with functional decline in bipolar affective disorder. Several characteristics previously considered specific to deterioration of functioning in schizophrenia, such as a high rate of birth complications and poor premorbid adjustment, appear to be associated with functional deterioration among patients with major depression as well.
Identification of candidate methylation-responsive genes in ovarian cancer
Authors: Laura Menendez, DeEtte Walker, Lilya V Matyunina, Erin B Dickerson, Nathan J Bowen, Nalini Polavarapu, Benedict B Benigno, John F McDonald
Journal: Molecular Cancer (2007)

Abstract Background Aberrant methylation of gene promoter regions has been linked to changes in gene expression in cancer development and progression. Genes associated with CpG islands (CGIs) are especially prone to methylation, but not all CGI-associated genes display changes in methylation patterns in cancers. Results In order to identify genes subject to regulation by methylation, we conducted gene expression profile analyses of an ovarian cancer cell line (OVCAR-3) before and after treatment with the demethylating agent 5-aza-deoxycytidine (5-aza-dC). An overlapping subset of these genes was found to display significant differences in gene expression between normal ovarian surface epithelial cells and malignant cells isolated from ovarian carcinomas. While 40% of all human genes are associated with CGIs, &gt; 94% of the overlapping subset of genes is associated with CGIs. The predicted change in methylation status of genes randomly selected from the overlapping subset was experimentally verified. Conclusion We conclude that correlating genes that are upregulated in response to 5-aza-dC treatment of cancer cell lines with genes that are down-regulated in cancer cells may be a useful method to identify genes experiencing epigenetic-mediated changes in expression over cancer development.
Aetiology of, and risk factors for, recurrent community-acquired pneumonia
Authors: C. Garcia-Vidal, J. Carratalà, N. Fernández-Sabé, J. Dorca, R. Verdaguer, F. Manresa, F. Gudiol
Journal: Clinical Microbiology and Infection (2009)

Recurrent community-acquired pneumonia (CAP) requiring hospitalization is a matter of particular concern. However, current information on its prevalence, aetiology and risk factors is lacking. To address these issues, we performed an observational analysis of a prospective cohort of hospitalized adults with CAP. Recurrence was defined as two or more episodes of CAP 1 month apart within 3 years. Patients with severe immunosuppression or local predisposing factors were excluded. Of the 1556 patients, 146 (9.4%) had recurrent CAP. The most frequent causative organism was Streptococcus pneumoniae, both in patients with recurrent CAP and in those without recurrence. Haemophilus influenzae, other Gram-negative bacilli and aspiration pneumonia were more frequent among patients with recurrent CAP, whereas Legionella pneumophila was rarely identified in this group. Independent factors associated with recurrent CAP were greater age, lack of pneumococcal vaccination, chronic obstructive pulmonary disease (COPD) and corticosteroid therapy. In a sub-analysis of 389 episodes of pneumococcal pneumonia, the only independent risk factor for recurrence was lack of pneumococcal vaccination. Recurrence of CAP is not a rare clinical problem and it occurs mainly in the elderly, patients with COPD, and those receiving corticosteroids. Our study provides support for recommending pneumococcal vaccination for adults at risk of pneumonia, including those with a first episode of CAP.
Tamoxifen and toremifene lower serum cholesterol by inhibition of delta 8-cholesterol conversion to lathosterol in women with breast cancer.
Authors: H Gylling, S Pyrhönen, E Mäntylä, H Mäenpää, L Kangas, T A Miettinen
Journal: Journal of Clinical Oncology (1995)

PURPOSE Long-term effects of tamoxifen and toremifene, a new antiestrogen that closely resembles tamoxifen, were investigated on serum lipids and cholesterol metabolism. PATIENTS AND METHODS The study group consisted of 24 postmenopausal Finnish women with advanced breast cancer from an international multicenter study of 415 patients. Cholesterol metabolism was evaluated by measuring the cholesterol precursor (delta 8-cholestenol, desmosterol, and lathosterol, reflecting cholesterol synthesis) and plant sterol (markers of cholesterol absorption) and cholestanol levels by gas-liquid chromatography. RESULTS Tamoxifen and toremifene lowered significantly serum low-density lipoprotein (LDL) cholesterol levels after 12 months of treatment by 16% and 15%, with no change in high-density lipoprotein (HDL) cholesterol or serum triglyceride levels. Serum delta 8-cholestenol was increased 40- and 55-fold during toremifene and tamoxifen treatment, respectively, while the increase of desmosterol less than doubled and was lacking for lathosterol by toremifene. Plant sterols and cholestanol were only inconsistently increased in serum. CONCLUSION Tamoxifen and toremifene inhibit the conversion of delta 8-cholestenol to lathosterol so that serum total and LDL cholesterol levels are lowered by downregulation of cholesterol synthesis. Thus, inhibition of the delta 8-isomerase may be the major hypolipidemic effect of these agents. Reduced risk of coronary artery disease will probably occur also during long-term toremifene treatment, because the drug reduces cholesterol and its synthesis, similarly to tamoxifen.
Comparison of exhaled nitric oxide values measured by two offline methods or NO breath
Authors: Ito Jun, Tsubrai Takahiro, Atsuta Ryo, Watai Kentaro, Minami Takashi, Hayashi Hiroaki, Sekiya Kiyoshi, Oshikata Chiyako, Tsurikizawa Naomi, Harada Norihiro, Mori Akio, Hasegawa Maki, Taniguchi Masami, Takahashi Kazuhisa, Akiyama Kazuo
Journal: European Respiratory Journal (2013)

BACKGROUND   The fraction of exhaled nitric oxde (FeNO) is a useful marker of eosinophilic airway inflammation in asthmatics. The FeNO measurement with two offline methods and NO breath may be more affordable, small number of studies have examined the differences in FeNO values measured with various methods in adult Japanese.   METHODS   The study population comprised 44 patient (male/female: 14/30; mean age: 51.8±15.0 years; bronchial asthma/other respiratory disorders: 27/17) at our hospital. FeNO value were measured by two offline methods (Sievers and CEIS), NO breath.   RESULTS   FeNO NO breath  value were significantly correlated with those FeNO Sievers  (r=0.87) and FeNO CEIS  (r=0.89). FeNO NO breath  values were nearly equal FeNO Sievers  (FeNO NO breath =1.1 x FeNO Sievers ), however these values were low compared with FeNO CEIS  (FeNO NO breath =0.75 x FeNO CEIS )(p=0.02).   CONCLUSION   Difference exist in the values of FeNO measured by various methods: conversion equations are needed to compare the FeNO values among these three methods.