tbuckley/cabot-search huggingface dataset:
Zoledronic acid and atrial fibrillation in cancer patients with bone metastases
Authors: S. Aksoy, Ö. Dizdar, D. Turgut, D. Sener Dede, Ç. Arslan, H. Harputluoglu, K. Altundag
Journal: Journal of Clinical Oncology (2009)

e20591 Background: Treatment with a bisphosphonate was linked with a significantly increased risk for atrial fibrillation (AF) in a few studies. Once-yearly infusions of intravenous zoledronic acid (ZA) was also significantly increased serious AF in postmenopausal women with osteoporosis. This study was conducted to determine the frequency of atrial fibrillation among cancer patients receiving the standard treatment of ZA. Methods: One hundred and twenty-four cancer patients who had bone metastasis receiving ZA were included in this study. All patients have been receiving 4 mg ZA at 4-week intervals; with each dose administered over 15 minutes. Patients who presented outpatient clinic for any reason (routine control, chemotherapy, ZA administration) a short survey completed and standard 12-lead ECG recordings were obtained. Results: One hundred and twenty-four cancer patients with documented bone metastases were evaluated. Mean age of the patients was 55 ± 13.0 years, 60% of the patients were female. Forty-one percent of the patients had breast cancer and 17% non-small cell lung cancer and the remainder had other solid tumors. Mean duration of ZA administration was 13.4 ± 15.0 months/patients. Mean total cumulative dose was 54 ± 15.0 mg per patients. 60 (48%) of the patients were treated with antracycline including regimens, and 37 (30%) were treated with mediastinal radiotherapy that might effect the heart. Twenty-three percent of the patients had hypertension, 10% diabetes mellitus, 7% currently smoker and 32% exsmoker, 3.7% myocardial infarction history, 1.9% congestive heart failure, and 1% valvular disease. On ECG evaluation; we observed sinus rhythm in 58%, sinus tachycardia in 15%, sinus bradicardia in 3.2%, ventricular exracystole in 5.7% of the patients. There were no AF. Conclusions: Although most of the patients were also having potentially cardiotoxic treatment, there was no increase in AF frequency in cancer patients who were treated with intravenous ZA. We believe that the risk of AF is small and may increase with age and comorbidity. No significant financial relationships to disclose.
Variability of response to lithium augmentation in refractory depression
Authors: L H Price, D S Charney, G R Heninger
Journal: American Journal of Psychiatry (1986)

Eighty-four patients with major depression refractory to a controlled antidepressant trial had lithium added to their ongoing treatment. Objective symptom ratings showed highly significant improvement in the sample as a whole. At discharge or after 24 days, 31% of the patients showed a marked response, 25% a partial response. Thus, 56% of patients had a significant positive response, while 44% were nonresponders. This study indicates that response to lithium augmentation may be quite variable and a 3-week trial is necessary to assess full benefit.
Integration of genetic and clinical risk factors improves prognostication in relapsed childhood B-cell precursor acute lymphoblastic leukemia
Authors: Julie A. E. Irving, Amir Enshaei, Catriona A. Parker, Rosemary Sutton, Roland P. Kuiper, Amy Erhorn, Lynne Minto, Nicola C. Venn, Tamara Law, Jiangyan Yu, Claire Schwab, Rosanna Davies, Elizabeth Matheson, Alysia Davies, Edwin Sonneveld, Monique L. den Boer, Sharon B. Love, Christine J. Harrison, Peter M. Hoogerbrugge, Tamas Revesz, Vaskar Saha, Anthony V. Moorman
Journal: Blood (2016)
Direct Hepatocyte Insulin Signaling Is Required for Lipogenesis but Is Dispensable for the Suppression of Glucose Production
Authors: Paul M. Titchenell, William J. Quinn, Mingjian Lu, Qingwei Chu, Wenyun Lu, Changhong Li, Helen Chen, Bobby R. Monks, Julia Chen, Joshua D. Rabinowitz, Morris J. Birnbaum
Journal: Cell Metabolism (2016)
Clinical and anatomical considerations for surgery in aortoiliac disease and results of surgical treatment.
Authors: Brewster Dc
Journal: Circulation (1991)

A variety of surgical procedures are available for the treatment of occlusive disease involving the aorta and iliac arteries. Use of the most appropriate operation in each patient, determined principally by disease location and patient risk, can provide highly effective relief of disabling claudication or limb-threatening ischemia with low morbidity and mortality rates. The excellent, durable results of current surgical practice should serve as the standard with which newer treatment modalities must be compared.
Abstract PR08: Evidence for extra-ovarian origin and peritoneal metastases that precede ovarian carcinomas in high-grade serous ovarian cancer.
Authors: Jeremy Chien, Viji Shridhar, Andrea Mariani
Journal: Clinical Cancer Research (2016)

Abstract High-grade serous (HGS) ovarian cancer is the most lethal form of epithelial ovarian cancer because it represents the most common histologic subtype and usually present at an advanced stage. Due to its advanced stage presentation, HGS ovarian cancer has been described as arising de novo from undefined precursor lesions that progress rapidly to advanced disease. To gain insights into clonal heterogeneity and progression to distant metastases, we analyzed single nucleotide variations (SNVs) from nine regions of carcinomas from four patients with HGS ovarian cancer. Three primary sites, three metastases from omentum, and three metastases from bowel were collected from each patient and subjected to RNA sequencing and SNV analysis. Although a modest number (23.62%) of SNVs are shared within the same anatomic site, only limited number (1.26%) of SNVs are shared among all 9 sites, suggesting a high degree of intratumor heterogeneity in these patients. Truncal mutations, such as TP53 mutations, are shared among all sites and observed at high allele frequencies. In addition, mutations in genes associated with epigenetic modifiers, such as SETD2, CHD8, KDM5A, SMARCA1 and ARID5B are observed as truncal mutations in these patients. Phylogenetic tree reconstruction of tumors from various sites suggests a concurrent ovarian and peritoneal metastases in one patient and peritoneal metastases preceding the ovarian carcinomas in three other patients. Finally, subclone inference from multi-region sequencing indicates the presence of multiple subclones at each site in these patients. Dominant subclones, present at metastases, are often ancestral clones in the clonal hierarchy, further providing evidence that peritoneal spreading occurs early in the clonal expansion. Collectively, these results provide evidence for early peritoneal spreading that often precedes ovarian carcinomas in HGS ovarian cancer. This abstract is also presented as Poster B44. Citation Format: Jeremy Chien, Viji Shridhar, Andrea Mariani. Evidence for extra-ovarian origin and peritoneal metastases that precede ovarian carcinomas in high-grade serous ovarian cancer. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research: Exploiting Vulnerabilities; Oct 17-20, 2015; Orlando, FL. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(2 Suppl):Abstract nr PR08.
Maternal Embryonic Leucine Zipper Kinase (MELK) as a Novel Mediator and Biomarker of Radioresistance in Human Breast Cancer
Authors: Corey Speers, Shuang G. Zhao, Vishal Kothari, Alyssa Santola, Meilan Liu, Kari Wilder-Romans, Joseph Evans, Nidhi Batra, Harry Bartelink, Daniel F. Hayes, Theodore S. Lawrence, Powel H. Brown, Lori J. Pierce, Felix Y. Feng
Journal: Clinical Cancer Research (2016)

While effective targeted therapies exist for estrogen receptor-positive and HER2-positive breast cancer, no such effective therapies exist for triple-negative breast cancer (TNBC); thus, it is clear that additional targets for radiosensitization and treatment are critically needed.Expression microarrays, qRT-PCR, and Western blotting were used to assess MELK RNA and protein expression levels. Clonogenic survival assays were used to quantitate the radiosensitivity of cell lines at baseline and after MELK inhibition. The effect of MELK knockdown on DNA damage repair kinetics was determined using γH2AX staining. The in vivo effect of MELK knockdown on radiosensitivity was performed using mouse xenograft models. Kaplan-Meier analysis was used to estimate local control and survival information, and a Cox proportional hazards model was constructed to identify potential factors impacting local recurrence-free survival.MELK expression is significantly elevated in breast cancer tissues compared with normal tissue as well as in TNBC compared with non-TNBC. MELK RNA and protein expression is significantly correlated with radioresistance in breast cancer cell lines. Inhibition of MELK (genetically and pharmacologically) induces radiation sensitivity in vitro and significantly delayed tumor growth in vivo in multiple models. Kaplan-Meier survival and multivariable analyses identify increasing MELK expression as being the strongest predictor of radioresistance and increased local recurrence in multiple independent datasets.Here, we identify MELK as a potential biomarker of radioresistance and target for radiosensitization in TNBC. Our results support the rationale for developing clinical strategies to inhibit MELK as a novel target in TNBC. Clin Cancer Res; 22(23); 5864-75. ©2016 AACR.
The Treatment of Small-Pox by Vaccination and Injection of Lymph
Authors: R. C. Furley
Journal: BMJ (1872)

IN the JOURNAL of the 4th May, I am censured for having written to a daily contemporary what I believe to be a fact-viz., that vaccination cures small-pox.I am aware that I was guilty of great impropriety, and that my conduct in so doing is from one point of view justly reprehensible; but I would ask to be allowed a word of justification.At the time when I wrote, half the city was under the impression that it was dangerous to be vaccinated when small-pox was raging; and some medical men with large practices were refusing to vaccinate under the same fear, and others because the former vaccination-mark was quite distinct.My letter was sent to a local paper (in which I have read the letters of great and honoured members of the profession on sanitary subjects), to dispel these ideas; and if ever an object aimed at was attained, it was that.In a few days, hundreds who had refrained from protecting themselves, were vaccinated; and some medical gentlemen were calling upon those to whom they had previously refused the only safeguard.I willingly therefore take all the odium attached to my proceeding, on account of the good it has done; at the same time, I regret the cause that gave occasion to it.In the same article, I am re- proached with not having read my data before the Medico-Chirurgical Society.It is not my fault, nor that of the President, that this has not, been done, but arises simply from the fact that there were more papers sent in than can be read and discussed this session.Relying on the statements and undoubtedly extensive experience of Mr. Marson and
Association of Acute Gastroesophageal Reflux Disease With Esophageal Histologic Changes
Authors: Kerry B. Dunbar, Agoston T. Agoston, Robert D. Odze, Xiaofang Huo, Thai H. Pham, Daisha J. Cipher, Donald O. Castell, Robert M. Genta, Rhonda F. Souza, Stuart J. Spechler
Journal: JAMA (2016)

The histologic changes associated with acute gastroesophageal reflux disease (GERD) have not been studied prospectively in humans. Recent studies in animals have challenged the traditional notion that reflux esophagitis develops when esophageal surface epithelial cells are exposed to lethal chemical injury from refluxed acid.To evaluate histologic features of esophageal inflammation in acute GERD to study its pathogenesis.Patients from the Dallas Veterans Affairs Medical Center who had reflux esophagitis successfully treated with proton pump inhibitors (PPIs) began 24-hour esophageal pH and impedance monitoring and esophagoscopy (including confocal laser endomicroscopy [CLE]) with biopsies from noneroded areas of distal esophagus at baseline (taking PPIs) and at 1 week and 2 weeks after stopping the PPI medication. Enrollment began May 2013 and follow-up ended July 2015.PPIs stopped for 2 weeks.Twelve patients (men, 11; mean age, 57.6 year [SD, 13.1]) completed the study. Primary outcome was change in esophageal inflammation 2 weeks after stopping the PPI medication, determined by comparing lymphocyte, eosinophil, and neutrophil infiltrates (each scored on a 0-3 scale) in esophageal biopsies. Also evaluated were changes in epithelial basal cell and papillary hyperplasia, surface erosions, intercellular space width, endoscopic grade of esophagitis, esophageal acid exposure, and mucosal impedance (an index of mucosal integrity).At 1 week and 2 weeks after discontinuation of PPIs, biopsies showed significant increases in intraepithelial lymphocytes, which were predominantly T cells (median [range]: 0 (0-2) at baseline vs 1 (1-2) at both 1 week [P = .005] and 2 weeks [P = .002]); neutrophils and eosinophils were few or absent. Biopsies also showed widening of intercellular spaces (confirmed by CLE), and basal cell and papillary hyperplasia developed without surface erosions. Two weeks after stopping the PPI medication, esophageal acid exposure increased (median: 1.2% at baseline to 17.8% at 2 weeks; Δ, 16.2% [95% CI, 4.4%-26.5%], P = .005), mucosal impedance decreased (mean: 2671.3 Ω at baseline to 1508.4 Ω at 2 weeks; Δ, 1162.9 Ω [95% CI, 629.9-1695.9], P = .001), and all patients had evidence of esophagitis.In this preliminary study of 12 patients with severe reflux esophagitis successfully treated with PPI therapy, stopping PPI medication was associated with T lymphocyte-predominant esophageal inflammation and basal cell and papillary hyperplasia without loss of surface cells. If replicated, these findings suggest that the pathogenesis of reflux esophagitis may be cytokine-mediated rather than the result of chemical injury.clinicaltrials.gov Identifier: NCT01733810.
Adverse cutaneous reactions to antidepressants
Authors: J K Warnock, J W Knesevich
Journal: American Journal of Psychiatry (1988)

The authors review the literature on adverse cutaneous reactions to antidepressant medications. The prevalence of rashes ranges from approximately 2% to 4% but is higher for certain antidepressants such as maprotiline and carbamazepine. Antidepressant drug reactions result in a variety of cutaneous morphologic patterns, but the majority of eruptions are exanthematous. The patterns of these reactions are similar whether the pathogenesis is mediated by immunologic or nonimmunologic mechanisms. The management of patients with adverse cutaneous reactions to antidepressants is discussed, and various recommendations are given.
Abstract P3-07-10: The association between the expression of progesterone receptor and clinical benefit of adjuvant trastuzumab in estrogen receptor-positive and HER2-positive breast cancer patients
Authors: HW Lee, SG Ahn, JT Park, BS Yang, S Park, J Jeong, SI Kim
Journal: Cancer Research (2016)

Abstract Background: Previous studies have shown that progesterone receptor (PR) status has a prognostic value in hormone receptor-positive breast cancer. In this study, we evaluated the clinical significance of PR status in estrogen receptor (ER)-positive and HER2-positive breast cancer. Methods: We retrospectively analyzed the data of ER+ and HER2+ breast cancer patients who underwent surgery at Gangnam Severance hospital and Severance hospital from 2002 to 2012. We excluded patients who had a history of previous cancer, received neoadjuvant chemotherapy, did not received adjuvant chemotherapy, and had contralateral breast cancer or metastasis at diagnosis. A total of 346 patients were identified. Among them, 155 patients (44.8%) received adjuvant trastuzumab. Results: At a median follow-up of 59 months, median disease-free survival (DFS) and overall survival (OS) were 56 and 59 months, respectively. The DFS and OS showed no difference according to PR status in overall patients. Then, these patients were categorized into two groups: ER+/HER2+/PR+ and ER+/HER2+/PR-. In ER+/HER2+PR+ patient, there was no difference of DFS or OS according to trastuzumab use. In ER+/HER2+/PR- patients, DFS was significantly better in patients who received adjuvant trastuzumab treatment compared to those who did not (p=0.009). We also analyzed influence of PR status on treatment outcome between patients who received adjuvant trastuzumab and those who did not. In patients who received adjuvant trastuzumab, there was no difference of DFS or OS according to PR status. However, in patients who did not receive adjuvant trastuzumab, ER+/HER2+/PR- patients showed worse DFS than ER+/HER2+/PR+ patients (p=0.006). Conclusions: In patients with ER+/HER2+ breast cancer, we found that a prognostic value of PR only retained in those who did not receive adjuvant trastuzumab. Our findings suggest that the use of adjuvant trastuzumab may offer less clinical benefit for the patients with ER+/HER2+/PR+ breast cancer. Citation Format: Lee HW, Ahn SG, Park JT, Yang BS, Park S, Jeong J, Kim SI. The association between the expression of progesterone receptor and clinical benefit of adjuvant trastuzumab in estrogen receptor-positive and HER2-positive breast cancer patients. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P3-07-10.
New agents for the treatment of drug-resistant Mycobacterium tuberculosis
Authors: Daniel T. Hoagland, Jiuyu Liu, Robin B. Lee, Richard E. Lee
Journal: Advanced Drug Delivery Reviews (2016)

Inadequate dosing and incomplete treatment regimens, coupled with the ability of the tuberculosis bacilli to cause latent infections that are tolerant of currently used drugs, have fueled the rise of multidrug-resistant tuberculosis (MDR-TB). Treatment of MDR-TB infections is a major clinical challenge that has few viable or effective solutions; therefore patients face a poor prognosis and years of treatment. This review focuses on emerging drug classes that have the potential for treating MDR-TB and highlights their particular strengths as leads including their mode of action, in vivo efficacy, and key medicinal chemistry properties. Examples include the newly approved drugs bedaquiline and delaminid, and other agents in clinical and late preclinical development pipeline for the treatment of MDR-TB. Herein, we discuss the challenges to developing drugs to treat tuberculosis and how the field has adapted to these difficulties, with an emphasis on drug discovery approaches that might produce more effective agents and treatment regimens.
Exploring the multidimensional aspects of grief reactions
Authors: L A Vargas, F Loya, J Hodde-Vargas
Journal: American Journal of Psychiatry (1989)

The authors explored the multidimensional aspects of early grief reactions in 201 relatives and close friends of victims of accidental deaths, suicides, homicides, and sudden natural deaths. A principal components analysis of a grief reaction measure revealed four factors: depressive symptoms, preservation of the lost object, suicidal ideation, and decedent-directed anger. The authors suggest that certain features which have been associated mostly with pathological grief (e.g., difficulty relinquishing the lost object) may be present in many, if not most, of the general population during bereavement and that pathology may best be determined by measuring the frequency and intensity of these features.
Noradrenergic activity and prediction of psychotic relapse following haloperidol withdrawal in schizophrenia
Authors: D P van Kammen, H Agren, J K Yao, D T O'Connor, J Gurklis, J L Peters
Journal: American Journal of Psychiatry (1994)

The purpose of this study was to develop a model based on the authors' previous studies to identify which neuroleptic-treated schizophrenic patients are at risk of early relapse following drug withdrawal.Clinical and CSF monoamine-related variables obtained for 50 male haloperidol-treated, schizophrenic patients were used in a logistic regression model to identify those who relapsed (N = 24) within 6 weeks after placebo substitution and those who did not (N = 26).The oral dose of haloperidol, weight, CSF norepinephrine, 3-methoxy-4-hydroxyphenylglycol and chromogranin A-like immunoreactivity, and the anxiety and paranoia subscale ratings of the Brief Psychiatric Rating Scale produced a model that correctly predicted 18 relapsers and 21 nonrelapsers. By including the interactions of paranoia subscale by CSF norepinephrine and anxiety by CSF norepinephrine, the model correctly identified 20 relapsers and 23 nonrelapsers with a sensitivity and specificity of 83% and 88%, respectively.Increased noradrenergic activity during chronic dopamine blockade may be an episode marker and may predict relapse within 6 weeks following haloperidol withdrawal in schizophrenia. Effective relapse prediction models have important practical implications for the treatment of schizophrenia and the understanding of the psychotic relapse process.
Elevation of serum squamous cell carcinoma antigen 2 in patients with psoriasis: associations with disease severity and response to the treatment
Authors: Y. Watanabe, Y. Yamaguchi, N. Komitsu, S. Ohta, Y. Azuma, K. Izuhara, M. Aihara
Journal: British Journal of Dermatology (2016)

Squamous cell carcinoma antigen (SCCA) belongs to the ovalbumin-serpin family and is a known tumour marker. Expression of SCCA is upregulated in the serum and skin of patients with psoriasis.The aim of this study was to determine SCCA2 levels in association with disease severity and treatment efficacy in patients with psoriasis.Patients with psoriasis (n = 123) and healthy controls (n = 25) were enrolled in this prospective cross-sectional study. Enzyme-linked immunosorbent assay (ELISA) analysis was performed to determine serum SCCA2 levels. SCCA2 expression in skin was evaluated using immunohistochemical analysis. Serum SCCA2 levels were compared with Psoriasis Area Severity Index (PASI) scores. The effect of treatment on serum SCCA2 levels was assessed using serial examinations. Induction of SCCA2 by several psoriatic cytokines in human keratinocytes was evaluated.The serum levels of SCCA2 were significantly higher in patients with psoriasis than healthy controls and correlated well with disease severity. Increased SCCA2 staining was observed in lesional skin but not in nonlesional skin of patients with psoriasis. In addition, SCCA2 expression levels in skin correlated with serum concentrations of SCCA2. SCCA2 significantly decreased according to improvement of PASI scores. Interleukin (IL)-17 and IL-22 synergistically increased the production of SCCA2 at both mRNA and protein levels in human keratinocytes.Significant elevation of SCCA2 is associated with disease severity and reflects treatment efficacy. SCCA2 may be a useful biomarker in psoriasis, reflecting T-helper 17-type inflammation - the main determinant of the severity of psoriasis.
FVIII-binding IgG modulates FVIII half-life in patients with severe and moderate hemophilia A without inhibitors
Authors: Christoph J. Hofbauer, Sylvia Kepa, Michael Schemper, Peter Quehenberger, Sylvia Reitter-Pfoertner, Christine Mannhalter, Birgit M. Reipert, Ingrid Pabinger
Journal: Blood (2016)