tbuckley/cabot-search huggingface dataset:
IL-33 signaling contributes to the pathogenesis of myeloproliferative neoplasms
Authors: Lukas F. Mager, Carsten Riether, Christian M. Schürch, Yara Banz, Marie-Hélène Wasmer, Regula Stuber, Alexandre P. Theocharides, Xiaohong Li, Yu Xia, Hirohisa Saito, Susumu Nakae, Gabriela M. Baerlocher, Markus G. Manz, Kathy D. McCoy, Andrew J. Macpherson, Adrian F. Ochsenbein, Bruce Beutler, Philippe Krebs
Journal: Journal of Clinical Investigation (2015)

Myeloproliferative neoplasms (MPNs) are characterized by the clonal expansion of one or more myeloid cell lineage. In most cases, proliferation of the malignant clone is ascribed to defined genetic alterations. MPNs are also associated with aberrant expression and activity of multiple cytokines; however, the mechanisms by which these cytokines contribute to disease pathogenesis are poorly understood. Here, we reveal a non-redundant role for steady-state IL-33 in supporting dysregulated myelopoiesis in a murine model of MPN. Genetic ablation of the IL-33 signaling pathway was sufficient and necessary to restore normal hematopoiesis and abrogate MPN-like disease in animals lacking the inositol phosphatase SHIP. Stromal cell–derived IL-33 stimulated the secretion of cytokines and growth factors by myeloid and non-hematopoietic cells of the BM, resulting in myeloproliferation in SHIP-deficient animals. Additionally, in the transgenic JAK2V617F model, the onset of MPN was delayed in animals lacking IL-33 in radio-resistant cells. In human BM, we detected increased numbers of IL-33–expressing cells, specifically in biopsies from MPN patients. Exogenous IL-33 promoted cytokine production and colony formation by primary CD34+ MPN stem/progenitor cells from patients. Moreover, IL-33 improved the survival of JAK2V617F-positive cell lines. Together, these data indicate a central role for IL-33 signaling in the pathogenesis of MPNs.
Intermittent screening and treatment or intermittent preventive treatment with dihydroartemisinin–piperaquine versus intermittent preventive treatment with sulfadoxine–pyrimethamine for the control of malaria during pregnancy in western Kenya: an open-label, three-group, randomised controlled superiority trial
Authors: Meghna Desai, Julie Gutman, Anne L'lanziva, Kephas Otieno, Elizabeth Juma, Simon Kariuki, Peter Ouma, Vincent Were, Kayla Laserson, Abraham Katana, John Williamson, Feiko O ter Kuile
Journal: The Lancet (2015)
Abstract 17519: Chronic Kidney Disease Blunts the Prognostic Significance of Chronotropic Incompetence during Exercise in Patients with Left Ventricular Dysfunction
Authors: Yusuke Sata, Hiroshi Takaki, Michio Nakanishi, Teruo Noguchi, Yoichi Goto, Masaru Sugimachi
Journal: Circulation (2010)

Background: An impaired heart rate response to exercise, chronotropic incompetence (CI), has been reported to be an independent predictor of cardiovascular mortality, but not disclosed elsewhere. T...
Open Access Exercise Electrocardiography: Does it Improve the Management of Cardiovascular Disease in the Community?
Authors: V E Paul, A N Sulke, A D C Norris
Journal: Journal of the Royal Society of Medicine (1990)

In this study the use of exercise electrocardiography, by 47 general practitioners in South East Kent has been evaluated. Of 110 consecutive requests the majority (88%) were for diagnostic purposes, while only 7% were for prognostic assessment. Many of those referred were young or had non-cardiac chest pain and in 59% of cases the test result was unlikely to alter the clinical assessment of the probability of ischaemic heart disease (IHD). The test result influenced patient management in 85% of cases. Only 15% of patients were subsequently referred to the district general hospital although all had been considered for referral prior to the test. Although referral for invasive investigation of six patients was expedited by the provision of stress testing, in five patients general practitioners failed to consider any further investigation despite the patient having a strongly positive test. General practitioners use exercise electrocardiography primarily to exclude IHD in patients at low risk and provide reassurance. They rarely use the test as a means to guide management of those with known or probable IHD.
Death in the parlour
Authors: Kevin Barraclough
Journal: BMJ (2001)

One of the unavoidable features of rural general practice is the proximity of suffering. At times it seems as though a miasma of pain and premature death hangs in little pockets around the valley, affecting patients, neighbours, and friends. As one stays longer in practice, the picturesque villages become shrouded with recollections not apparent to the casual visitor.

As a trainee I was told that this was a privilege, a claim I viewed then, and now, with some ambivalence. There …
Effect of tamoxifen on endometrial proliferation.
Authors: A Decensi, V Fontana, S Bruno, C Gustavino, B Gatteschi, A Costa
Journal: Journal of Clinical Oncology (1996)

PURPOSE An increase in the incidence of endometrial cancer and a potential increase in related mortality has been associated with the administration of 20 mg tamoxifen, the dose adopted in breast cancer chemoprevention trials, thus urging studies on intermediate markers of risk. PATIENTS AND METHODS Thirty-three women who received 20 mg tamoxifen as adjuvant breast cancer treatment underwent endometrial biopsy. Samples were divided for histologic examination, including a quantitative analysis of stromal:epithelial ratio, and an assessment of DNA ploidy and proliferation by flow cytometry. Results were compared with 37 symptomatic subjects. RESULTS All histograms were DNA diploid. Compared with controls, a significant increase in the risk of proliferation as measured by the hyperdiploid fraction was associated with tamoxifen duration (&lt; or = 36 months: cumulative odds ratio = 16.5, 95% confidence interval, 1.85 to 146.5; &gt; 36 months: cumulative odds ratio = 28.2, 95% confidence interval, 2.56 to 310.6, P for trend &lt; .05). Tamoxifen-induced risk was significantly reduced by the extent of menopausal status. No cases of cancer or epithelial hyperplasia were observed in the tamoxifen group, whereas seven cases of epithelial hyperplasia without atypia were observed in the control group. The effect of tamoxifen on proliferation was associated with an increase in the stromal component. CONCLUSION Tamoxifen at 20 mg/d exerts a time-dependent proliferative effect on the endometrium, particularly in premenopausal and early postmenopausal women. This effect appears to be mediated by the stromal component, which accounts for the discrepancy between flow cytometry and histology. Our study provides preliminary evidence that the DNA flow cytometric hyperdiploid fraction may be a useful tool for monitoring endometrial cell proliferation in women exposed to tamoxifen.
Diagnostic yield, safety and utilisation of EBUS-TBNA under conscious sedation
Authors: Usman Maqsood, Selva Selvaraj, Michael Healy, Kambiz Malcki, Mazhar Chaudri
Journal: European Respiratory Journal (2013)

Objectives:   To look at the utilisation of EBUS in a UK DGH and evaluate its safety, utility and diagnostic yield.   Methods:   Data was analysed retrospectively on the first one hundred cases of EBUS guided TBNA. The procedure was done under conscious sedation with use of 2.5-5 mg of Midazolam and 50-100 mcg of Fentanyl alongwith lignocaine throat spray and transtracheal injection. The procedure was done with supplementary oxygen given (range 2-8 L/min, Mean 2.2L, Median 2L) to patients via nasal speculum.   Results:   100 patients (37% females) underwent the procedure over a period of 2.5 years. Patients’ ages ranged from 32 to 88 (Mean 70, Median 69). Their FEV1 ranged from 0.7 to 3.5 (Mean 1.85, Median 1.82) and their FEV1% ranged from 26% to 121% (Mean 69.5%, Median 71%). The pre-procedure oxygen saturation ranged between 82% to 100% (Mean 95.4, Median 96%). Mininum oxygen saturation during the procedure ranged between 80-100% (Mean 92%, Median 94%). 63 patients (63%) were found to have malignant disease. Diagnostic yield and complication rate were comparable with published data¹. There were no complications or mortality following the procedure.   Conclusion:   EBUS-TBNA under conscious sedation in a UK DGH appears to be safe and effective in the diagnosis of mediastinal lymphadenopathy. However, referral for mediastinoscopy is still required for equivocal EBUS guided TBNA samples.   Reference:   1.EBUS guided TBNA for mediastinal masses. (NICE Feb, 2008).
Pathologic Features May Predict the Clinical Outcome of Hepatic Graft Versus Host Disease (H-GVHD).
Authors: Rafael F. Duarte, Julio Delgado-Gonzalez, Bronwen E. Shaw, David Wrench, Mark Ethell, David Patch, Amar P. Dhillon, Stephen Mackinnon, Michael Potter, Alberto F. Quaglia
Journal: Blood (2004)
Reply
Authors: Peipei Lu, Wen Xie
Journal: Hepatology (2015)

Supported in part by NIH grant DK083952. Potential conflict of interest: Nothing to report. Author names in bold designate shared co‐first authorship. Reply: We appreciate Drs. Vinciguerra and Mazzoccoli's comments on our findings about the aryl hydrocarbon receptor/fibroblast growth factor 21 (AHR‐FGF21) endocrine pathway in the dissociation of diet‐induced fatty liver from insulin resistance. We understand that the circadian clock machinery plays an important role in regulating energy balance, and this regulation involves a number of central and peripheral tissues, including the liver. There are a myriad of examples that genetic alterations in clock genes led to metabolic dysfunctions. AHR is a PAS domain transcriptional factor known to play a role in circadian control.1 Indeed, activation of AHR by dioxins has been reported to inhibit clock gene expression and disrupt the circadian clock.1 Therefore, it is possible that the transgenic (TG) activation of AHR in our TG mice could have altered circadian rhythmicity, which might have contributed to the observed metabolic phenotypes. To specifically address the Vinciguerra and Mazzoccoli comments, we measured the hepatic expression of several core clock genes, including Clock, Per1, and Per2, in mice maintained on chow diet or treated with the high‐fat diet (HFD). We found that expression of Clock, Per1, and Per2 was decreased in CA‐AHR TG mice in both the chow‐fed and HFD‐fed conditions (Fig. 1). These results are consistent with the previous reports that TCDD and other xenobiotics could influence circadian gene expression.1 Future studies are necessary to determine whether TG activation of AHR alters the oscillation pattern of clock genes.Figure 1: Activation of AHR suppressed hepatic expression of circadian clock genes. Wild‐type (WT) and CA‐AHR TG mice were fed with chow diet for 14 weeks or HFD for 12 weeks. Shown are the hepatic messenger RNA (mRNA) expressions of Clock, Per1, and Per2 as measured by real‐time polymerase chain reaction.One of our most interesting findings is the establishment of FGF21 as a novel AHR target gene.2 Again, in our animal model, it remains to be determined whether TG activation of AHR alters the circadian rhythmicity and, if so, whether the circadian pattern of FGF21, as an AHR target gene, will be changed. To our knowledge, the circadian regulation of FGF21 and the mechanism of this circadian regulation are not as well established as the fasting‐responsive regulation of FGF21.3 The nocturnal rise of serum FGF21 in humans may be involved in the regulation of glucose homeostasis during the night.4 In principle, the AHR in our TG mice is constitutively activated throughout the day, so it is likely that the sustained increase in circulating FGF21 may have contributed to the metabolic benefits observed in our TG mice. This interpretation is consistent with the reports that chronic administration of recombinant FGF21 protein or TG overexpression of FGF215 was sufficient to confer the metabolic benefits.
Abstract 4298: Trends, Predictors, and Outcomes of Stroke Related to Percutaneous Coronary Intervention: A Fifteen Year Single Center Experience
Authors: Scott Hoffman, Robert Simari, Charanjit Rihal, David Holmes, Riyaz Bashir, Ryan Lennon, Alejandro Rabinstein, Rajiv Gulati
Journal: Circulation (2009)

Aims We sought to determine temporal trends, predictors, in-hospital and long-term outcomes of stroke related to percutaneous coronary intervention (PCI) over a 15 year period. Methods and results ...
Incidence of peripheral neuropathy during daily TB chemotherapy: Indian experience
Authors: Tushar Sahasrabudhe, Vikas Oswal
Journal: European Respiratory Journal (2011)

It is a routine practice to prescribe prophylactic pyridoxine to patients on TB chemotherapy to prevent Isoniazide induced neuropathy. However this adverse effect seems to be uncommon in our experience. We did a prospective study to determine the incidence of peripheral neuropathy in patients on daily TB chemotherapy. A total of 559 patients on standard daily TB chemotherapy as per WHO categorization were followed throughout the course of treatment. No patient received prophylactic pyridoxine. Patients with proven or suspected drug resistance were excluded from the study. Patients with existing peripheral neuropathy or those suffering from a condition predisposing to neuropathy such as diabetes, were also excluded. Patients reporting with symptoms of peripheral neuropathy such as tingling, numbness and other paraesthesias during the TB chemotherapy were followed. Other causes of neuropathy were ruled out. They were given daily vitamin B-complex (containing Pyridoxine 3 mg) one tablet thrice a day for one week. They were given 100 mg Pyridoxine daily only if there was no response. A total of 26/559 patients (4.65%) developed neuropathy symptoms. 19/26 (73.07%) patients responded to one week course of B-complex and never had recurrence of symptoms. 7/559 (1.25%) patients needed 100 mg of pyridoxine to relieve their symptoms. This indicates very low incidence of peripheral neuropathy in patients on daily TB chemotherapy without use of prophylactic pyridoxine, in Indian scenario.
Chronic Iron Deposition following Acute Hemorrhagic Myocardial Infarction: A Cardiovascular Magnetic Resonance Study
Authors: Avinash Kali, Andreas Kumar, Ivan Cokic, Richard Tang, Sotirios Tsaftaris, Matthias Friedrich, Rohan Dharmakumar
Journal: Circulation (2012)

Introduction - Intramyocardial hemorrhage frequently occurs in large reperfused myocardial infarctions (MI). However, its long-term fate remains unexplored.

Hypothesis - We hypothesize that intramyocardial hemorrhage, secondary to reperfused MI, results in chronic iron deposition within infarcted territories.

Methods - We studied 15 patients by Cardiovascular Magnetic Resonance (CMR) T2* mapping (1.5T) on day 3 and 6 months after successful percutaneous coronary intervention for first STEMI. Using the same CMR protocol, we also studied 20 canines, on days 3 and 56 post ischemia-reperfusion injury, of which 3 animals received sham procedures. Subsequently, canine hearts were explanted, imaged ex-vivo, and samples of hemorrhagic infarcts (Hemo+), non-hemorrhagic infarcts (Hemo-), remote and sham myocardium were isolated, sectioned and mass spectrometry was performed.

Results - Eleven patients had Hemo+ (verified by T2* CMR on day 3) and their scar tissue T2* values remained significantly lower after 6 months, when compared to Hemo- and remote myocardium (Fig 1; p<0.001). In canines, Hemo+ territories showed a significant T2* reduction compared to the other groups (Fig 2; p<0.001). Mean iron content ([Fe]) of Hemo+ on day 56 was 10-fold greater than that observed in control groups (p<0.001), while no differences were observed among the control groups (p=0.14). A strong linear relationship was observed between log(T2*) and -log([Fe]) (R2 = 0.74; p<0.001) on day 56. Conclusion - Hemorrhagic MI leads to chronic iron depositions within the infarct zones. Consequences of chronic iron deposition within the scar tissue remain to be investigated.
The prevalence of attention deficit disorder, residual type, or minimal brain dysfunction, in a population of male alcoholic patients
Authors: Wood D, Wender Ph, Reimherr Fw
Journal: American Journal of Psychiatry (1983)

The authors assessed the prevalence of attention deficit disorder, residual type, in a population of young adult male alcoholic patients in two residential alcohol treatment programs. They found the prevalence of the disorder in this sample to be 33% and hypothesize that attention deficit disorder in childhood (and adulthood) may be associated with an increased risk for the development of alcoholism. If substantiated, this finding could be of theoretical and therapeutic importance.
Low level of FoxP3 in bronchial asthma (BA) is associated with frequent exacerbations
Authors: Natalya Kirillova, Elena Kremer, Ludmila Ogorodova, Ivan Deev, Evgeniy Kulikov, Olga Fedorova, Polina Selivanova
Journal: European Respiratory Journal (2012)

Background. Regulatory T cells (T-reg) expressing FOXP3 inhibit the development of T cells towards Th2. In this work we hypothesized that FoxP3 is responsible for the development of exacerbations in asthma.  Aim and objectives. To investigate the levels of CD4+FOXP3+ in moderate BA with different frequency of exacerbations compared to healthy donors.  Methods. We included 20 patients with moderate asthma, which were divided into 2 groups. The first group (n=16) had at least 1 exacerbation of asthma during the previous year, the disease duration was 7,5 (3,0:12,0) years, FEV1 - 81,2 (72,2:89,4)%. The second group (n=4) with moderate BA had 2 or more exacerbations of asthma in the previous year, the duration of the disease was 14,5 (9,0:23,0) years, FEV1 - 78,4 (74,4:89,8)%. The control group was included 17 healthy adults. Peripheral blood mononuclear cells were isolated in Ficoll density. The circulating percentage of CD4+FoxP3+ T-regs in peripheral blood was estimated by the flow cytometry analysis (FACSCalibur Becton Dickinson, USA) using appropriate monoclonal antibodies.  Results. It was found that moderate asthma is characterized by significantly lower CD4+FoxP3+ T-reg 0,99 (0,72:3,77)% compared to healthy control - 8,16 (7,66:9,42)% (p  Conclusions. FoxP3 is responsible for the development of exacerbations in asthma. Possible, the low level of transcription factor FoxP3 is closely related to 2 or more exacerbations of BA per year.
Pulmonary hydatidosis mimicking metastatic malignancy
Authors: Samira Aouadi, Imen Bachouche, Sonia Maalej, Meriem Mjid, Mahrezia Bourguiba, Ali Ben Kheder, Ikram Drira
Journal: European Respiratory Journal (2011)

Scattered pulmonary nodules are usually highly suspicious of metastatic malignancy, but can be one of radiological presentations of some infectious diseases such as hydatidosis. In order to analyse particularities of pulmonary hydatidosis mimicking metastatic malignancy, we report 5 cases of patients hospitalized in the pulmonary department of the Tunis Chest Disease and Surgery Training Hospital.  The average age was between 36 and 74 years. The clinical features were dominated by haemoptysis (4 cases) and cough (2 cases). Chest radiograph showed disseminated pulmonary opacities in all cases. CT scan of the chest was helpful for diagnosis. Fibreoptic endoscopy performed in all cases showed hydatic membrane and confirmed the diagnosis in 2 patients. Investigation ELISA for Echinococcus was positive in all cases. Four patients had pulmonary embolic hydatidosis due to the involvement of right cardiac cavities. One patient had bronchogenic hydatidosis due to the rupture of pulmonary cysts into bronchi. Medical treatment (albendazole) was performed in all patients associated with surgical treatment in 2 cases. After treatment, 2 cases of recurrence were noted.  Disseminated pulmonary hydatidosis may present diagnosis difficulties particularly with metastatic malignancy. Its management is difficult and costly.
Abstract 3488: HPV detection by PCR in real time in peruvian women
Authors: Javier Manrique, Gustavo Sarria, Abelardo Arias, Pamela Mora, Abel Limache, Maria del Carmen Nuñez, Yasser Sullcahuaman, Tatiana Vidaurre
Journal: Cancer Research (2014)

Abstract Background. In Perú Cervical cancer is a significant public health problem, according Globocan, it is the most frequent cancer among women in Peru, the incidence of this cancer is 34.5 and the mortality 16.3. In 2004, cervical cancer was responsible of 66,771 DALYs in Peru, 18.2% of the total. The human papillomavirus (HPV) is a well-known cause of cervical cancer. HPV tests are used as an adjunct test to decrease the false-negative rate of cytological screening. The HPV test will permit to separate the population in two groups, women with high risk to cancer cervical (HPV+) and women with low risk to cancer cervical (HPV-). Objective. To identify the prevalence of the genotypes of Human Papillomavirus (HPV) in Peruvian women from marginal urban area of Lima according age. Methodology. Samples of 5460 women aged 18 to 63 years were studied for analysis by the automated Roche Cobas 4800 system that detects genotypes 16 and 18 specifically and 12 other genotypes (31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, 66) considered high risk HPV, for this purpose the system uses specific primers for the L1 region of the viral genome and control the system using B globin gene. Results and Conclusions. According PCR screening the total samples were 5,460 (100%), 855 (15.62%) were positive by PCR, of the PCR positive 319 were positive by CBL (5.84%), 16 of them were LIE-AG (0.29%) and 0 carcinomas. The genotypes of PVH more frequent was 16 (16%), genotype 16 plus others high risk virus was 69 (8%), PVH 18 was 8 (3%). Of the 853 women that were positive for PCR, 149 of them had the highest risk HPV genotype 16 and the age group that most often present for this genotype was 30 to 39 years, this group is consider as high risk population. In general, PCR have been demonstrated an adequate prevalence rate of women in high risk according of other literature and we consider as an important test to cervical cancer control. Ilustración 1. Frequency of HPV in Peruvian women. Illustration 2. HPV Genotypes in peruvian women Illustration 3. Distribution of CBL (+) Ilustración 3. Genotipos de PVH y distribución por grupo etáreo. / HPV genotype distribution per age group. Citation Format: Javier Manrique, Gustavo Sarria, Abelardo Arias, Pamela Mora, Abel Limache, Maria del Carmen Nuñez, Yasser Sullcahuaman, Tatiana Vidaurre. HPV detection by PCR in real time in peruvian women. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3488. doi:10.1158/1538-7445.AM2014-3488