tbuckley/cabot-search huggingface dataset:
Analysis of EGFR-mutations in a diverse urban patient population
Authors: Amanda Tufman, Kai Wagner, Andreas Jung, Rudolf Maria Huber
Journal: European Respiratory Journal (2011)

Background:  EGFR-mutations are predictive for EGFR-TKIs in advanced NSCLC; however, not all pts are screened for these mutations. Clinical criteria (female, never-smoker, East-Asian, adeno-ca) are often used to select pts, however the impact of country of origin in non-East Asians has not yet been described. We analysed EGFR-mutation and country of origin in NSCLC pts treated at a university hospital in Munich.   Methods:  We retrospectively identified all pts treated for primary thoracic malignancy on the ward in 3 months and conducted a chart review. Specimens were analysed for activating mutations in exons 18, 19, 21, using nested PCR together with tailed primers (bidirectional didesoxi-sequencing applying the tail-sequences as sequencing primers on a Genetic Analyzer 3130 platform - Applied Biosystems).   Results:  From Oct to Dec 2009, 62 pts with thoracic malignancies (NSCLC 52, SCLC 7, carcinoid 1, mesothelioma 2) were treated. Country of origin: Ethiopia 1, Mongolia 1, Italy 2, Spain 1, Russia 1, Croatia 4 (6.5%), Turkey 9 (14.5%), Germany 43 (69.4%). Subtypes of NSCLC: adeno 48.1, large cell 3.8, squamous 40.4, NOS 7.7%. 53 samples are analyzed, and revealed 4 activating mutations and one pt with silent mutations in exon 18 and 20. Activating mutations were found in 3/43 (7%) Germans (including a heavy smoker with squamous cell ca, 1 adeno, 1 large cell), 1/9 (11%) Turks and 2 silent mutations were found in 1/4 Croatians (adeno).   Discussion:  Regional mutational heterogeneity occurs in various illnesses. In NSCLC this affects the generalisability of study data. In this first analysis we describe the diverse nature of a patient population in Munich, and show similar rates of activating EGFR mutation in all subgroups.
Imaging the swollen joint in the young patient.
Authors: A Coral, C S Orgles, A Harvey
Journal: Annals of the Rheumatic Diseases (1995)

Clinical history A four year old boy presented to an orthopaedic surgeon with a painful swollen left ankle, having been treated for tonsillitis one week previously.Blood count, plasma viscosity and C reactive protein were normal.Radiological findings A lateral radiograph (fig 1) showed distension of the anterior recess of the tibiotalar joint capsule, indicating joint disease.The joint was not aspirated.Intravenous gadolinium-diethylene triamino pentacetic acid (IV Gd-DTPA) enhanced magnetic resonance imaging (MRI) showed that the distension of the anterior recess consisted predominantly of synovial thickening around a minor effusion (fig 2).Effusions were present in all the tendon sheaths posteriorly and in tibialis anterior(fig 3).
The vegetative state
Authors: M. M. Monti, S. Laureys, A. M. Owen
Journal: BMJ (2010)

#### Summary points

The vegetative state may develop suddenly (as a consequence of traumatic or non-traumatic brain injury, such as hypoxia or anoxia; infection; or haemorrhage) or gradually (in the course of a neurodegenerative disorder, such as Alzheimer’s disease). Although uncommon, the condition is perplexing because there is an apparent dissociation between the two cardinal elements of consciousness: awareness and wakefulness.1 Patients in a vegetative state appear to be awake but lack any sign of awareness of themselves or their environment.w1 Large retrospective clinical audits have shown that as many as 40% of patients with a diagnosis of vegetative state may in fact retain some level of consciousness. Misdiagnosis has many implications for a patient’s care—such as day to day management, access to early interventions, and quality of life—and has ethical and legal ramifications pertaining to decisions on the discontinuation of life supporting …
Impact of Spin in the Abstracts of Articles Reporting Results of Randomized Controlled Trials in the Field of Cancer: The SPIIN Randomized Controlled Trial
Authors: Isabelle Boutron, Douglas G. Altman, Sally Hopewell, Francisco Vera-Badillo, Ian Tannock, Philippe Ravaud
Journal: Journal of Clinical Oncology (2014)

We aimed to assess the impact of spin (ie, reporting to convince readers that the beneficial effect of the experimental treatment is greater than shown by the results) on the interpretation of results of abstracts of randomized controlled trials (RCTs) in the field of cancer.
Induction of p53 Expression in Skin by Radiotherapy and UV Radiation: a Randomized Study
Authors: F. Ponten, H. Lindman, A. Bostrom, B. Berne, J. Bergh
Journal: JNCI Journal of the National Cancer Institute (2001)

Background: p53 protein plays an important role in the response to DNA damage, and radiotherapy can cause radiation dermatitis. p53 and p21 levels increase in vitro when DNA is damaged by UVA, UVB, or γ-radiation. To determine whether this response occurs in human skin and predicts the level of radiation dermatitis, we investigated levels of p53 and p21 in skin exposed to different types of radiation as part of a randomized study of women with breast cancer to evaluate topical steroid or emollient cream treatments for radiation dermatitis of their irradiated breast. Methods: After surgery but before receiving tangential 5-mV photo-beam radiotherapy (2 Gy and 54 Gy) to the affected breast parenchyma, multiple areas on the backs of 50 women were irradiated with UVA and other areas were irradiated with UVB. Skin biopsy samples were taken from areas of normal unirradiated skin and all irradiated areas, and p53 and p21 were detected immunohistochemically. All statistical tests are two-sided. Results: In skin irradiated with UVA or UVB, medians of 4.4% (range = 0%–40.5%) or 45.5% (range = 5.3%–74.6%) p53-positive keratinocytes, respectively, were observed. Radiotherapy produced medians of 31.0% (range = 0%–79.3%) p53-immunoreactive cells after 2 Gy of radiation and 83.2% (range = 37.6%–95.2%) after 54 Gy of radiation. Despite large interindividual differences in p53 response, comparable increases in epidermal p53 response were independent of the type of radiation. A correlation between p53 and p21 was also evident (rs = .78). In breast skin, there was no association between the p53 response and the degree of erythema (a measure of radiation dermatitis) and no statistically significant difference between treatment arms and p21/p53 responses. Conclusions: Individual responses to radiation-induced DNA damage varied widely and may be independent of the type of radiation. The epidermal p53 response does not predict the degree of radiation dermatitis.
Endobronchial hamartoma presenting as massive haemoptysis
Authors: RA Sharkey, EM Mulloy, S O'Neill
Journal: European Respiratory Journal (1996)

A 53 year old man presented with massive haemoptysis, and chest radiography revealed a left suprahilar mass. At thoracotomy he was found to have a modular mass in the left upper lobe, which was attached to a peripheral bronchus. Histology confirmed a pulmonary hamartoma.
Induction of Vascular Insulin Resistance and Endothelin-1 Expression and Acceleration of Atherosclerosis by the Overexpression of Protein Kinase C-β Isoform in the Endothelium
Authors: Qian Li, Kyoungmin Park, Chenzhong Li, Christian Rask-Madsen, Akira Mima, Weier Qi, Koji Mizutani, Paul Huang, George L. King
Journal: Circulation Research (2013)

Loss of insulin action in the endothelium can cause endothelial dysfunction and atherosclerosis. Hyperglycemia and elevated fatty acids induced by diabetes mellitus can activate protein kinase C-β isoforms and selectively inhibit insulin signaling via phosphatidylinositol 3-kinase/Akt pathway to inhibit the activation of endothelial nitric oxide synthase and metabolic actions.
Randomized Phase II Study of the Neurokinin 1 Receptor Antagonist CJ-11,974 in the Control of Cisplatin-Induced Emesis
Authors: P. J. Hesketh, R. J. Gralla, R. T. Webb, W. Ueno, S. DelPrete, M. E. Bachinsky, N. L. Dirlam, C. B. Stack, S. L. Silberman
Journal: Journal of Clinical Oncology (1999)

PURPOSE: To determine the efficacy and safety of the neurokinin type 1 receptor antagonist CJ-11,974 for the control of high-dose cisplatin-induced emesis. PATIENTS AND METHODS: A double-blind, randomized, phase II design with a group sequential stopping rule was used in this study. Sixty-one patients with cancer who were receiving cisplatin at a dose of at least 100 mg/m 2 for the first time were enrolled. All patients received granisetron 10 μg/kg and dexamethasone 20 mg intravenously 30 minutes before they were given cisplatin. Patients were randomly assigned to two groups: group 1 received CJ-11,974 100 mg, and group 2 received placebo orally 30 minutes before and 12 hours after cisplatin and then twice daily on days 2 through 5 after cisplatin. The primary end point was the percentage of patients who developed delayed emesis (emesis on the second to fifth days after cisplatin). RESULTS: Thirty patients were enrolled in group 1, and 31 patients were enrolled in group 2. Fifty-eight patients were assessable for efficacy. Complete control of emesis (expressed as the percentage of patients who had no emesis) was as follows: day 1, 85.7% (group 1) and 66.7% (group 2) (P = .090); days 2 through 5, 67.8% (group 1) and 36.6% (group 2) (P = .0425, adjusted); days 1 through 5, 64.3% (group 1) and 30% (group 2) (P = .009). Patients in group 1 experienced significantly less nausea than patients in group 2 on day 1 (P = .024). Treatment was well tolerated in both groups. CONCLUSION: We conclude from this exploratory phase II trial that CJ-11,974 is superior to placebo in controlling cisplatin-induced delayed emesis and may provide additive benefit in acute emesis and nausea control when combined with a 5-hydroxytryptamine-3 receptor antagonist and dexamethasone. Additional larger trials are indicated to confirm the clinical value of CJ-11,974.
Clinical outcome and microbiological findings using antibiotic-loaded spacers in two-stage revision of prosthetic joint infections
Authors: Javier Cabo, Gorane Euba, Anna Saborido, María González-Panisello, María Angeles Domínguez, Jose L. Agulló, Oscar Murillo, Ricard Verdaguer, Javier Ariza
Journal: Journal of Infection (2011)
Elevated Numbers of Tissue-Factor Exposing Microparticles Correlate With Components of the Metabolic Syndrome in Uncomplicated Type 2 Diabetes Mellitus
Authors: Michaela Diamant, Rienk Nieuwland, Renée F. Pablo, Augueste Sturk, Jan W.A. Smit, Jasper K. Radder
Journal: Circulation (2002)

Type 2 diabetes is associated with accelerated atherosclerosis. Because cell-derived microparticles support coagulation and inflammation, they may be involved in atherogenesis. We characterized circulating microparticles both in patients with uncomplicated, well-regulated type 2 diabetes and in healthy subjects, as well as their relationship with coagulation and metabolic control.Microparticles were isolated from plasma, stained with annexin V, cell-specific monoclonal antibodies (MoAbs) and a MoAb directed against tissue factor (TF), and analyzed by flow cytometry. Microparticle numbers and origin were comparable in the two groups, but the median number of TF-positive microparticles was twice as high in patients than in controls (P=0.018). Patients had higher percentages of TF-positive microparticles from T-helper cells (P=0.045), granulocytes (P=0.004), and platelets (P=0.002). Subpopulations of TF-positive microparticles from platelets and T-helper cells exposed granulocytic markers. Correlations were found between the numbers of various TF-positive microparticle subpopulations and body mass index, fasting plasma glucose and insulin, or tumor necrosis factor-alpha and serum HDL cholesterol. Microparticles from patients generated less thrombin in vitro (P=0.007). Microparticle numbers did not correlate with in vivo coagulation markers prothrombin fragment F(1+2) and thrombin-antithrombin complexes.TF, possibly of granulocytic origin, is exposed on microparticle subpopulations in asymptomatic patients with well-regulated type 2 diabetes. TF-positive microparticles are associated with components of the metabolic syndrome but not with coagulation. Thus, TF on microparticles may be involved in processes other than coagulation, including transcellular signaling or angiogenesis.
THE KINEMATIC ANALYSIS OF FEMALE SUBJECTS AFTER DOUBLE-BUNDLE ANTERIOR CRUCIATE LIGAMENT RECONSTRUCTION DURING SINGLE-LEG SQUATTING
Authors: J Yamazaki, T Muneta, YJ Ju, H Koga, T Morito, I Sekiya
Journal: British Journal of Sports Medicine (2014)

Background The kinematic characteristics of female anterior cruciate ligament (ACL)-injured subjects were recognized in our previous study using an electromagnetic device comparing both female control groups and male ACL-injured subjects during single-leg squatting. Objective To assess the kinematic characteristics of female subjects after double-bundle ACL reconstruction during single-leg squatting. Design Case control study. Participants Female patients after double-bundle ACL reconstruction. Risk factor assessment Three-dimensional motion analysis was performed for single-leg squatting in female subjects after ACL reconstruction. We evaluated the relative angles between the pelvis, thigh, and lower leg using an electromagnetic device during single-leg squatting in 28 female subjects with ACL reconstruction. All patients included in this study restored their sports performance level to 90% or higher. Main outcome measurements The lower limb of female subjects after double-bundle ACL reconstruction exhibited asymmetric kinematic results during single-leg squatting in comparison with the involved leg with the uninjured leg. Results Comparing the involved leg to the uninjured leg of female subjects after ACL reconstruction, the involved leg demonstrated significantly more hip adduction and less knee varus than the uninjured leg. Comparing the ACL-reconstructed female subjects to the healthy female controls, the involved leg after ACL reconstruction demonstrated significantly less hip flexion, more hip external rotation, more hip adduction, and more knee flexion than the dominant leg of the control group. Conclusion This kinematic study exhibited kinematic characteristics of ACL-reconstructed knees of female subjects. Double-bundle ACL reconstruction could not quite restore the normal kinematics of female-involved legs compared with both uninjured legs of female subjects and healthy female controls. In future studies, restoring the correct alignment of ACL reconstructed knee during single-leg squatting would be expected to reduce ACL re-injury and to assist a safe return to sport activities.
Fucoidan induces apoptosis of human HS-Sultan cells accompanied by activation of caspase-3 and down-regulation of ERK Pathways
Authors: Yoshinobu Aisa, Yoshitaka Miyakawa, Tomonori Nakazato, Hideyuki Shibata, Kaori Saito, Yasuo Ikeda, Masahiro Kizaki
Journal: American Journal of Hematology (2004)

Fucoidan, a sulfated polysaccharide in brown seaweed, was found to inhibit proliferation and induce apoptosis in human lymphoma HS-Sultan cell lines. Fucoidan-induced apoptosis was accompanied by the activation of caspase-3 and was partially prevented by pretreatment with a pan-caspase inhibitor, z-VAD-FMK. The mitochondrial potential in HS-Sultan cells was decreased 24 hr after treatment with fucoidan, indicating that fucoidan induced apoptosis through a mitochondrial pathway. When HS-Sultan was treated with 100 μg/mL fucoidan for 24 hr, phosphorylation of ERK and GSK markedly decreased. In contrast, phosphorylation of p38 and Akt was not altered by treatment with fucoidan. l-Selectin and P-selectin are known to be receptors of fucoidan; however, as HS-Sultan does not express either of these selectins, it is unlikely that fucoidan induced apoptosis through them in HS-Sultan. The neutralizing antibody, Dreg56, against human l-selectin did not prevent the inhibitory effect of fucoidan on the proliferation of IM9 and MOLT4 cells, both of which express l-selectin; thus it is possible fucoidan induced apoptosis though different receptors. These results demonstrate that fucoidan has direct anti-cancer effects on human HS-Sultan cells through caspase and ERK pathways. Am. J. Hematol. 78:7–14, 2005. © 2004 Wiley-Liss, Inc.
Isolation, Structure Elucidation, and Synthesis of a Macrophage Stimulatory Lipopeptide from <i>Mycoplasma fermentans</i> Acting at Picomolar Concentration
Authors: Peter F. Mühlradt, Michael Kieß, Holger Meyer, Roderich Süßmuth, Günther Jung
Journal: The Journal of Experimental Medicine (1997)

Macrophages are typically stimulated by components of microbial cell walls. Surprisingly, cell wall–less mycoplasmas can also very efficiently stimulate macrophages. We showed recently that mycoplasma-derived lipopeptides constitute the active principle. We have now isolated a clone of Mycoplasma fermentans expressing mainly one macrophage-stimulating lipopeptide. This lipopeptide was detergent-extracted and isolated by reversed-phase high-performance liquid chromotography, using nitric oxide release from C3H/HeJ mouse macrophages as bioassay for detection. In contrast to “conventional” bacterial lipoproteins, this lipopeptide had a free NH2 terminus. Amino acid composition, sequence, and the molecular weight of 2,163.3 are consistent with the following structure: S-(2,3-bisacyloxypropyl)cysteine-GNNDESNISFKEK with one mole C16:0, and a further mole of a mixture of C18:0 and C18:1 fatty acid per lipopeptide molecule. The sequence could not be found in either the protein identification resource nor the Swiss Prot data bank. We named this 2-kD lipopeptide, macrophage-activating lipopeptide-2 (MALP-2). Synthetic dipalmitoyl MALP-2 and mycoplasma-derived MALP-2 were compared with the bioassay. Both lipopeptides showed an identical dose dependency with a half-maximal response at 10−11 M concentration. MALP-2 may be one of the most potent natural macrophage stimulators besides endotoxin.
Nocturnal intermittent hypoxia predicts prevalent hypertension in the European Sleep Apnoea Database cohort study
Authors: Ruzena Tkacova, Walter T. McNicholas, Martin Javorsky, Ingo Fietze, Pawel Sliwinski, Gianfranco Parati, Ludger Grote, Jan Hedner
Journal: European Respiratory Journal (2014)

Systemic hypertension is associated with obstructive sleep apnoea syndrome (OSAS) but the pathophysiological mechanisms are incompletely understood. A collaborative European network of 24 sleep centres established a European Sleep Apnoea Database to evaluate cardiovascular morbidity associated with OSAS. 11 911 adults referred with suspected OSAS between March 2007 and September 2013 underwent overnight sleep studies, either cardiorespiratory polygraphy or polysomnography. We compared the predictive value of the apnoea–hypopnoea index (AHI) and 4% oxygen desaturation index (ODI) for prevalent hypertension, adjusting for relevant covariates including age, smoking, obesity, dyslipidaemia and diabetes. Among patients (70% male, mean± sd age 52±12 years), 78% had AHI &gt;5 events·h −1 and 41% systemic hypertension. Both AHI and ODI independently related to prevalent hypertension after adjustment for relevant covariates (p&lt;0.0001 for linear trend across quartiles (Q) of severity for both variables). However, in multiple regression analysis with both ODI and AHI in the model, ODI was, whereas AHI was not, independently associated with prevalent hypertension: odds ratios (95% CI) for Q4 versus Q1 regarding ODI were 2.01 (1.61–2.51) and regarding AHI were 0.92 (0.74–1.15) (p&lt;0.0001 and p=0.3054, respectively). This cross sectional study suggests that chronic intermittent hypoxia plays an important role in OSAS-related hypertension.
<i>TET2</i> Mutations Improve the New European LeukemiaNet Risk Classification of Acute Myeloid Leukemia: A Cancer and Leukemia Group B Study
Authors: Klaus H. Metzeler, Kati Maharry, Michael D. Radmacher, Krzysztof Mrózek, Dean Margeson, Heiko Becker, John Curfman, Kelsi B. Holland, Sebastian Schwind, Susan P. Whitman, Yue-Zhong Wu, William Blum, Bayard L. Powell, Thomas H. Carter, Meir Wetzler, Joseph O. Moore, Jonathan E. Kolitz, Maria R. Baer, Andrew J. Carroll, Richard A. Larson, Michael A. Caligiuri, Guido Marcucci, Clara D. Bloomfield
Journal: Journal of Clinical Oncology (2011)

Purpose To determine the frequency of TET2 mutations, their associations with clinical and molecular characteristics and outcome, and the associated gene- and microRNA-expression signatures in patients with primary cytogenetically normal acute myeloid leukemia (CN-AML). Patients and Methods Four-hundred twenty-seven patients with CN-AML were analyzed for TET2 mutations by polymerase chain reaction and direct sequencing and for established prognostic gene mutations. Gene- and microRNA-expression profiles were derived using microarrays. Results TET2 mutations, found in 23% of patients, were associated with older age (P &lt; .001) and higher pretreatment WBC (P = .04) compared with wild-type TET2 (TET2-wt). In the European LeukemiaNet (ELN) favorable-risk group (patients with CN-AML who have mutated CEBPA and/or mutated NPM1 without FLT3 internal tandem duplication [FLT3-ITD]), TET2-mutated patients had shorter event-free survival (EFS; P &lt; .001) because of a lower complete remission (CR) rate (P = .007), and shorter disease-free survival (DFS; P = .003), and also had shorter overall survival (P = .001) compared with TET2-wt patients. TET2 mutations were not associated with outcomes in the ELN intermediate-I–risk group (CN-AML with wild-type CEBPA and wild-type NPM1 and/or FLT3-ITD). In multivariable models, TET2 mutations were associated with shorter EFS (P = .004), lower CR rate (P = .03), and shorter DFS (P = .05) only among favorable-risk CN-AML patients. We identified a TET2 mutation-associated gene-expression signature in favorable-risk but not in intermediate-I–risk patients and found distinct mutation-associated microRNA signatures in both ELN groups. Conclusion TET2 mutations improve the ELN molecular-risk classification in primary CN-AML because of their adverse prognostic impact in an otherwise favorable-risk patient subset. Our data suggest that these patients may be candidates for alternative therapies.
Intensification of Statin Therapy Results in a Rapid Reduction in Atherosclerotic Inflammation
Authors: Ahmed Tawakol, Zahi A. Fayad, Robin Mogg, Achilles Alon, Michael T. Klimas, Hayes Dansky, Sharath S. Subramanian, Amr Abdelbaky, James H.F. Rudd, Michael E. Farkouh, Irene O. Nunes, Chan R. Beals, Sudha S. Shankar
Journal: Journal of the American College of Cardiology (2013)
The effect of uncomplicated potassium depletion on urine acidification
Authors: Richard L. Tannen
Journal: Journal of Clinical Investigation (1970)

Studies were performed on normal human subjects to determine the effects of potassium depletion on urine acidification. Depletion was induced by ingestion of a low potassium diet either alone or in combination with a potassium-binding resin, and the response of each subject to an acute ammonium chloride load in the potassium-depleted state was compared to his normal response. Urine pH was significantly higher during potassium deficiency if sufficient potassium depletion had been induced. No differences in blood acid-base parameters, urinary flow rate, or urinary fixed buffer excretion rate were found to account for this change; however, the increase in urine pH was accompanied by a concomitant increase in net acid and ammonium excretion. It is proposed that these changes during potassium depletion reflect an increase in ammonia diffusion into the urine, presumably as a result of increased renal ammonia production. In addition, it is speculated that changes in ammonia metabolism may be a physiologic control mechanism for potassium conservation.
Oral fludarabine in untreated patients with B-cell chronic lymphocytic leukemia
Authors: C Shustik, A R Turner, P Desjardins, L Fernandez, S Rubin, L Larratt, A M V Duncan, D Rizi, A Sadura, L Shepherd, D Li, L Rassenti, T Kipps
Journal: Leukemia (2009)