tbuckley/cabot-search huggingface dataset:
Blood Oxygenation Level–Dependent Magnetic Resonance Imaging of the Skeletal Muscle in Patients With Peripheral Arterial Occlusive Disease
Authors: Hans -Peter Ledermann, Anja-Carina Schulte, Hanns-Georg Heidecker, Markus Aschwanden, Kurt A. Jäger, Klaus Scheffler, Wolfgang Steinbrich, Deniz Bilecen
Journal: Circulation (2006)

Blood oxygenation level-dependent (BOLD) magnetic resonance imaging (MRI) has been used to measure T2* changes in skeletal muscle tissue of healthy volunteers. The BOLD effect is assumed to primarily reflect changes in blood oxygenation at the tissue level. We compared the calf muscle BOLD response of patients with peripheral arterial occlusive disease (PAOD) to that of an age-matched non-PAOD group during postischemic reactive hyperemia.PAOD patients (n=17) with symptoms of intermittent calf claudication and an age-matched non-PAOD group (n=11) underwent T2*-weighted single-shot multiecho planar imaging on a whole-body magnetic resonance scanner at 1.5 T. Muscle BOLD MRI of the calf was performed during reactive hyperemia provoked by a cuff-compression paradigm. T2* maps were generated with an automated fitting procedure. Maximal T2* change (deltaT2*(max)) and time to peak to reach deltaT2*(max) for gastrocnemius, soleus, tibial anterior, and peroneal muscle were evaluated. Compared with the non-PAOD group, patients revealed significantly lower deltaT2*(max)-values, with a mean of 7.3+/-5.3% versus 13.1+/-5.6% (P<0.001), and significantly delayed time-to-peak values, with a mean of 109.3+/-79.3 versus 32.2+/-13.3 seconds (P<0.001).T2* time courses of the muscle BOLD MRI signal during postocclusive reactive hyperemia revealed statistically significant differences in the key parameters (deltaT2*(max); time to peak) in PAOD patients compared with age-matched non-PAOD controls.
Inhaled corticosteroids in COPD: the clinical evidence
Authors: Pierre Ernst, Nathalie Saad, Samy Suissa
Journal: European Respiratory Journal (2014)

In this article, we focus on the scientific evidence from randomised trials supporting treatment with inhaled corticosteroids (ICS) in chronic obstructive pulmonary disease (COPD), including treatment with combinations of long-acting β-agonist (LABA) bronchodilators and ICS. Our emphasis is on the methodological strengths and limitations that guide the conclusions that may be drawn. The evidence of benefit of ICS and, therefore, of the LABA/ICS combinations in COPD is limited by major methodological problems. From the data reviewed herein, we conclude that there is no survival benefit independent of the effect of long-acting bronchodilation and no effect on FEV 1 decline, and that the possible benefit on reducing severe exacerbations is unclear. Our interpretation of the data is that there are substantial adverse effects from the use of ICS in patients with COPD, most notably severe pneumonia resulting in excess deaths. Currently, the most reliable predictor of response to ICS in COPD is the presence of eosinophilic inflammation in the sputum. There is an urgent need for better markers of benefit and risk that can be tested in randomised trials for use in routine specialist practice. Given the overall safety and effectiveness of long-acting bronchodilators in subjects without an asthma component to their COPD, we believe use of such agents without an associated ICS should be favoured.
Reduced Expression of the<i>Breast Cancer Metastasis Suppressor 1</i>mRNA Is Correlated with Poor Progress in Breast Cancer
Authors: Zhenhuan Zhang, Hiroko Yamashita, Tatsuya Toyama, Yutaka Yamamoto, Teru Kawasoe, Hirotaka Iwase
Journal: Clinical Cancer Research (2006)

Abstract Purpose: It is well established that breast cancer metastasis suppressor 1 (BRMS1) suppresses metastasis of breast cancer in animal models without affecting the growth of the primary tumor. It has also been shown to suppress the metastasis of tumors derived from breast and melanoma cell lines. However, its clinical importance for breast cancer patients remains undetermined. This prompted us to investigate its expression level in breast cancer patients to clarify its clinical significance. Experimental Design: The level of expression of BRMS1 mRNA was assessed by LightCycler quantitative real-time reverse transcription-PCR in 161 cases of invasive carcinoma of the breast. Associations between BRMS1 mRNA expression and various clinicopathologic factors were sought. Results: It was found that BRMS1 mRNA was expressed at significantly higher levels in patients &amp;gt;50 years of age, with tumor size &amp;lt;2 cm, or with progesterone receptor–positive and HER2-negative tumors. No differences were found between BRMS1 mRNA expression and axillary lymph node metastasis and histologic grade groups. Patients with high levels of expression of BRMS1 mRNA have a better prognosis than those with low expression. Univariate and multivariate prognostic analysis showed that BRMS1 mRNA is an independent prognostic factor for disease-free survival in breast cancer. Conclusions: These results provide clinical evidence to support the notion that BRMS1 is a breast carcinoma metastasis suppressor gene. Our results also suggest that measuring BRMS1 expression will help to identify those breast cancer patients with worse disease-free survival.
P17.16 * PRIMARY CENTRAL NERVOUS SYSTEM TUMORS IN YOUNG ADULTS: PATHOLOGY AND TREATMENT RESULTS
Authors: D. M. Cernea, S. Halasag, R. Stahiescu, N. Todor, S. Florian, V. I. Cernea
Journal: Neuro-Oncology (2014)

BACKGROUND: the scope of this study is to assess the pathologic type of brain tumors and the treatment results in young patients. PATIENTS AND METHODS: 85 patients with primary brain tumors, aged 18 to 39 years, with a median of 30 years, have been treated between 2005-2012, in Oncology Institute Cluj-Napoca. The distribution of patients according to histologic type was: grade 2 tumors (astrocytomas, oligodendrogliomas, ependymomas) 26 patients, (30,55%); grade 3 and 4 tumors (anaplastic astro cytomas, glioblastomas, oligodendrogliomas, ependymomas) 39 patients (45,88%); medulloblastomas 7 patients (8,24%) and other types (chondrosarcoma, sarcoma, adenoma, pinealocitoma, pinealoblastoma, meningioma, neuroblastoma, chordoma and 3 PNET tumors) 13 patients (15,29%). Surgery as first treatment was performed in all patients and was followed by radiotherapy in 54 patients (63,53%) and by radiotherapy and chemotherapy in 31 patients. Medulloblastomas have been treated with surgery and craniospinal radiotherapy. The tumor location was in spinal cord in 10 patients, in posterior cerebellar fossa in 13 patients and in supratentorial area in 59 patients. RESULTS: the patients have been followed between 9 (minimum) and 37 (maximum) months with maximum 87 months. The overall survival for the entire group is 51% at 5 years (limits 40%-62%). There are 38 patients alive and 47 deaths. The 5 years survival is 65% for patients with grade 2 astrocytomas, 45% for patients with malignant astrocytomas, 38% for medulloblastomas and 62% for patients with different other histological type. CONCLUSIONS: the pathology of primary brain tumors in young adults is more diverse than in older patients. Identifying groups of patients according which the treatment complexity must be increased is mandatory in order to improve survival. Cognitive functions and quality of life of these patients must be an important end point.
Impact on Survival and Toxicity by Duration of Weight Extremes During Treatment for Pediatric Acute Lymphoblastic Leukemia: A Report From the Children's Oncology Group
Authors: Etan Orgel, Richard Sposto, Jemily Malvar, Nita L. Seibel, Elena Ladas, Paul S. Gaynon, David R. Freyer
Journal: Journal of Clinical Oncology (2014)

Purpose Previous studies regarding the influence of weight on event-free survival (EFS) and treatment-related toxicity (TRT) in childhood acute lymphoblastic leukemia (ALL) considered only weight at diagnosis. Inasmuch as weight varies substantially over treatment, we hypothesized its impact on EFS is instead determined by cumulative time spent at an extreme weight during therapy and on TRT by weight at the time of toxicity. Patients and Methods In a cohort of 2,008 children treated for high-risk ALL in Children's Oncology Group study CCG-1961, we determined the effect on EFS of cumulative time receiving therapy at an extreme weight (either obese or underweight) between end of induction and start of maintenance therapy. We also evaluated the association between weight category and incidence and patterns of TRT during 13,946 treatment courses. Results Being obese or underweight at diagnosis and for ≥ 50% of the time between end of induction and start of maintenance therapy resulted in inferior EFS (hazard ratios, 1.43 and 2.30, respectively; global P &lt; .001). Normalization of weight during that period resulted in mitigation of this risk comparable to never being obese or underweight. Obese or underweight status at start of each treatment course was significantly associated with specific patterns of TRT. Conclusion Influence of weight extremes on EFS and TRT is not set at diagnosis as previously reported but is moderated by subsequent weight status during intensive postinduction treatment phases. These observations suggest that weight is a potentially addressable risk factor to improve EFS and morbidity in pediatric ALL.
Survivin Is a Therapeutic Target in Merkel Cell Carcinoma
Authors: Reety Arora, Masahiro Shuda, Anna Guastafierro, Huichen Feng, Tuna Toptan, Yanis Tolstov, Daniel Normolle, Laura L. Vollmer, Andreas Vogt, Alexander Dömling, Jeffrey L. Brodsky, Yuan Chang, Patrick S. Moore
Journal: Science Translational Medicine (2012)

A targeted therapy for a virus-induced cancer involves blockade of the cellular oncoprotein survivin.
The immune response of allophenic mice to the synthetic polymer L-glutamic acid, L-lysine, L-phenylalanine. II. Lack of gene complementation in two nonresponder strains
Authors: CM Warner, JL McIvor, PH Maurer, CF Merryman
Journal: The Journal of Experimental Medicine (1977)

The genetic control of the immune response of inbred strains of mice to certain antigens has been demonstrated to be governed by a set of Ir genes linked to the major histocompatibility complex (H-2) of mice (1,2). Until recently, the control was thought to be governed by single, dominant genes, located within the I region of the H-2 complex. Merryman et al. (3) originally demonstrated that the immune response to the synthetic terpolymer L-glutamic acid, L-lysine, L-phenylaline (GLφ) is under dominant, H-2-linked Ir gene control (4-7). This was shown both by crossing two nonresponder parental strains to produce responder offspring in the F(1) generation, and by the analysis of appropriate recombinant stains of mice. The two complementing genes have been mapped in the IA and IC regions of the H-2 complex, and have been termed β and α, respectively (5,6). Thus, any strain of mouse may contain neither, one, or both genes. Only mice containing both genes are capable of responding to GLφ. It has been shown using F(1) hybrid and recombinant strains of mice, that the α- and β-genes can complement each other in either the cis (on the same chromosome) or in the trans (on different chromosomes) position (8). In this paper we report the results of studies aimed at answering the question of whether or not the α- and β- genes can complement each other when they are present in different lymphoid cells. To this end we have constructed allophenic mice composed of two nonresponder strains (A and C57BL/6), which show gene complementation in the F(1) generation. Allophenic mice are chimeras containing two cell types coexisting in a normal environment. The mice were tested for the specific cellular composition of the two parental cell types and were found to possess a complete range in the relative proportion of the two cell types. This report demonstrates that regardless of the mixture of cell types present in the allophenic mice, none of them were responders to GLφ. Thus no complementation of the α- and β-genes is seen when the two genes are present in different cells.
Early assessment of diaphragmatic dysfunction in children in the ITU: chest radiology and phrenic nerve stimulation
Authors: RI Russell, BA Helps, CM Dicks-Mireaux, PJ Helms
Journal: European Respiratory Journal (1993)

Diaphragmatic dysfunction is a common postoperative complication of cardiac surgery in children, with important effects on respiratory morbidity. Its early diagnosis, followed by prompt surgical intervention, has been shown to reduce morbidity. However, the commonest method of diagnosis, based on hemi-diaphragmatic elevation on the chest radiograph, may be less accurate than direct techniques for assessing phrenic nerve function. We have compared electrophysiological and radiological diagnoses of diaphragmatic abnormality in 100 children (aged 3 days to 17.5 yrs) undergoing cardiac surgery, looking at respiratory morbidity as assessed by the duration of ventilation, the time spent on the cardiac intensive care unit (CICU), and the requirement for reintubation. Despite showing good reproducibility, radiological diagnosis was neither sensitive nor specific in identifying patients with electrophysiological phrenic nerve damage. Analysis of the measures of outcome supported the electrophysiological technique. Patients with electrophysiological evidence of damage had a longer duration of ventilation, spent longer on the CICU, and had a greater incidence of reintubation than either radiologically abnormal or "normal" patients. Chest X-rays are not a good method for diagnosing phrenic nerve damage in the early postoperative period in children. If early diagnosis is needed, then direct assessment of phrenic nerve function, such as the measurement of phrenic latency, may be a better technique.
Noninvasive identification of left-sided heart failure in a population suspected of pulmonary arterial hypertension
Authors: Wouter Jacobs, Thelma C. Konings, Martijn W. Heymans, Anco Boonstra, Harm Jan Bogaard, Albert C. van Rossum, Anton Vonk Noordegraaf
Journal: European Respiratory Journal (2015)

Exclusion of pulmonary hypertension secondary to left-sided heart disease (left heart failure (LHF)) is pivotal in the diagnosis of pulmonary arterial hypertension (PAH). In case of doubt, invasive measurements are recommended. The aim of the present study was to investigate whether it is possible to diagnose LHF using noninvasive parameters in a population suspected of PAH.300 PAH and 80 LHF patients attended our pulmonary hypertension clinic before August 2010, and were used to build the predictive model. 79 PAH and 55 LHF patients attended our clinic from August 2010, and were used for prospective validation.A medical history of left heart disease, S deflection in V1 plus R deflection in V6 in millimetres on ECG, and left atrial dilation or left valvular heart disease that is worse than mild on echocardiography were independent predictors of LHF. The derived risk score system showed good predictive characteristics: R(2)=0.66 and area under the curve 0.93. In patients with a risk score ≥72, there is 100% certainty that the cause of pulmonary hypertension is LHF. Using this risk score system, the number of right heart catheterisations in LHF may be reduced by 20%.In a population referred under suspicion of PAH, a predictive model incorporating medical history, ECG and echocardiography data can diagnose LHF noninvasively in a substantial percentage of cases.
Endothelin Peptide and Receptors in Human Atherosclerotic Coronary Artery and Aorta
Authors: Caragh R. Bacon, Nathaniel R.B. Cary, Anthony P. Davenport
Journal: Circulation Research (1996)

The aim of this study was to determine whether there is an alteration in the distribution or quantity of endothelin (ET) peptide or receptor subtypes in human atherosclerotic arteries. Levels of endogenous ET and big ET-1 detectable by radioimmunoassay in human aorta containing raised atherosclerotic plaques were significantly higher than those in histologically normal tissue (Student's t test, P &lt;.01). Immunohistochemistry revealed ET-like immunoreactivity in endothelial cells lining the vessel lumen, neovascularization, recanalization of organized thrombus, and regions rich in macrophages. Little immunoreactivity was associated with vascular smooth muscle cells (VSMCs). Saturation binding assays with [ 125 I]ET-1 indicated comparable affinities and maximal densities of receptors in the media of diseased and normal coronary arteries. Quantitative autoradiography with subtype-selective radioligands revealed similar small proportions of ET B receptors in the diseased and normal arterial media. In arteries with early and late disease, ET A receptors were localized to medial smooth muscle but were lacking in the VSMCs of the intimal layer, where ET B receptors were absent. ET B receptors were detected on perivascular nerves and lymphoid aggregates. In atherosclerotic arteries, microautoradiography localized ET B receptors to neovascularization and, interestingly, to macrophages. The results of this study indicate that there is an increase in ET and big ET-1 associated with fully developed atherosclerotic plaques. It is likely that this is derived from endothelial cells and macrophages but not VSMCs. ET A receptors predominate in the media of both normal and diseased arteries. ET receptors are deficient in intimal smooth muscle, and ET B receptors, where present, are found on endothelial cells and macrophages.
Most calcium pyrophosphate crystals appear as non-birefringent
Authors: J. Ivorra, J. Rosas, E. Pascual
Journal: Annals of the Rheumatic Diseases (1999)

To determine the proportion of calcium pyrophosphate dihydrate (CPPD) crystals that appear as non-birefringent when observed under the polarised light microscope.Two observers examined independently 10 synovial fluid samples obtained during an episode of arthritis attributable to CPPD crystals. Ten synovial fluid samples from patients with acute gout were used as a reference. The examination was performed after placing a fluid sample in a Niebauer haemocytometric chamber; a crystal count was done first under ordinary light, then in the area corresponding to a 0.1 ml, under polarised lightThe percentages of birefringence appreciated for CPPD were 18% (confidence intervals (CI) 12, 24) for observer 1, and 17% (CI 10, 24) for observer 2 (difference NS). The percentages of birefringence for monosodium urate were 127% (CI 103, 151) for observer 1 and 107% (CI 100, 114) for observer 2 (difference NS). Percentages above 100% indicate that crystals missed under ordinary light became apparent under polarised light.Only about one fifth of all CPPD crystals identified by bright field microscopy show birefringence when the same synovial fluid sample is observed under polarised light. If a search for CPPD crystals is conducted under polarised light, the majority of the crystals will be missed. Ordinary light allows a better rate of CPPD crystal detection but observation under polarised light of crystals showing birefringence is required for definitive CPPD crystal identification.
APOL1 Risk Variants Are Strongly Associated with HIV-Associated Nephropathy in Black South Africans
Authors: Alex N. Kasembeli, Raquel Duarte, Michèle Ramsay, Pulane Mosiane, Caroline Dickens, Thérèse Dix-Peek, Sophie Limou, Efe Sezgin, George W. Nelson, Agnes B. Fogo, Stewart Goetsch, Jeffrey B. Kopp, Cheryl A. Winkler, Saraladevi Naicker
Journal: Journal of the American Society of Nephrology (2015)

APOL1 variants are associated with HIV-associated nephropathy and FSGS in African Americans. The prevalence of these variants in African populations with CKD in HIV-1 infection has not been investigated. We determined the role of APOL1 variants in 120 patients with HIV-associated nephropathy and CKD and 108 controls from a South-African black population. Patients with CKD were selected on the basis of histology. Genotypes were successfully determined for APOL1 G1 and G2 variants and 42 single nucleotide polymorphisms, including 18 ancestry informative markers, for 116 patients with CKD (96.7%; 38 patients with HIV-associated nephropathy, 39 patients with HIV-positive CKD, and 39 patients with HIV-negative CKD), and 108 controls (100%). Overall, 79% of patients with HIV-associated nephropathy and 2% of population controls carried two risk alleles. In a recessive model, individuals carrying any combination of two APOL1 risk alleles had 89-fold higher odds (95% confidence interval, 18 to 912; P<0.001) of developing HIV-associated nephropathy compared with HIV-positive controls. Population allele frequencies were 7.3% for G1 and 11.1% for G2. APOL1 risk alleles were not significantly associated with other forms of CKD. These results indicate HIV-positive, antiretroviral therapy-naïve South-African blacks with two APOL1 risk alleles are at very high risk for developing HIV-associated nephropathy. Further studies are required to determine the effect of APOL1 risk variants on kidney diseases in other regions of sub-Saharan Africa.
UK trainee experience in interstitial lung disease: results from a British Thoracic Society survey
Authors: Charles Sharp, Toby M Maher, Sally Welham, Michael Gibbons
Journal: Thorax (2014)

Interstitial lung disease (ILD) is a growing field of respiratory medicine in which novel therapies are emerging. It is important that trainees gain competence and confidence in this area. To explore the training experiences of specialty trainees, we conducted a survey of their practical experience and confidence in diagnosing and managing ILD.
Renoprotective Effect of Combined Inhibition of Angiotensin-Converting Enzyme and Histone Deacetylase
Authors: Yifei Zhong, Edward Y. Chen, Ruijie Liu, Peter Y. Chuang, Sandeep K. Mallipattu, Christopher M. Tan, Neil R. Clark, Yueyi Deng, Paul E. Klotman, Avi Ma’ayan, John Cijiang He
Journal: Journal of the American Society of Nephrology (2013)

The Connectivity Map database contains microarray signatures of gene expression derived from approximately 6000 experiments that examined the effects of approximately 1300 single drugs on several human cancer cell lines. We used these data to prioritize pairs of drugs expected to reverse the changes in gene expression observed in the kidneys of a mouse model of HIV-associated nephropathy (Tg26 mice). We predicted that the combination of an angiotensin-converting enzyme (ACE) inhibitor and a histone deacetylase inhibitor would maximally reverse the disease-associated expression of genes in the kidneys of these mice. Testing the combination of these inhibitors in Tg26 mice revealed an additive renoprotective effect, as suggested by reduction of proteinuria, improvement of renal function, and attenuation of kidney injury. Furthermore, we observed the predicted treatment-associated changes in the expression of selected genes and pathway components. In summary, these data suggest that the combination of an ACE inhibitor and a histone deacetylase inhibitor could have therapeutic potential for various kidney diseases. In addition, this study provides proof-of-concept that drug-induced expression signatures have potential use in predicting the effects of combination drug therapy.