tbuckley/cabot-search huggingface dataset:
NH2-terminal globular domain of human platelet glycoprotein Ib alpha has a methionine 145/threonine145 amino acid polymorphism, which is associated with the HPA-2 (Ko) alloantigens.
Authors: R W Kuijpers, N M Faber, H T Cuypers, W H Ouwehand, A E von dem Borne
Journal: Journal of Clinical Investigation (1992)

The glycoprotein (GP) Ib/IX complex, a prominent platelet GP complex, is the primary receptor for vWF. Previously, we have established that an antigenic polymorphism of platelets, the HPA-2 or Ko alloantigen system, is located on the 45-kD amino-terminal globular domain of GPIb alpha. With the polymerase chain reaction, we have amplified two segments of the GPIb alpha gene coding for the first 382 amino acids of two HPA-2a and two HPA-2b homozygous individuals. Nucleotide sequence analysis revealed as the only difference a C-T polymorphism at position 434 of the coding region for the mature protein. This base change results in a substitution of threonine (ACG) in HPA-2a (Kob) to methionine (ATG) in HPA-2b (Koa) at amino acid position 145. The C-T polymorphism is reflected in a difference in restriction enzyme recognition, resulting in an Aha 2-site in the HPA-2b allele and a SfaN1 site in the HPA-2a allele. Restriction fragment length polymorphism analysis of the amplified DNA of 3 HPA-2(a-,b+), 2 HPA-2(a+,b+), and 11 HPA-2(a+,b-) donors showed that these restriction sites were associated with the HPA-2 alleles. DNA-typing for the HPA-2 alloantigen system on genomic DNA obtained from a small number of cells may be applied for determining the genotype of a fetus from an immunized mother or of severely thrombocytopenic patients.
Cystic Fibrosis Pulmonary Guidelines
Authors: Patrick A. Flume, Peter J. Mogayzel, Karen A. Robinson, Christopher H. Goss, Randall L. Rosenblatt, Robert J. Kuhn, Bruce C. Marshall
Journal: American Journal of Respiratory and Critical Care Medicine (2009)

Section:ChooseTop of pageAbstract <<METHODSRECOMMENDATIONSCONCLUSIONSReferencesCITING ARTICLES
Serum YKL-40 Predicts Relapse-Free and Overall Survival in Patients With American Joint Committee on Cancer Stage I and II Melanoma
Authors: Henrik Schmidt, Julia S. Johansen, Pia Sjoegren, Ib J. Christensen, Boe S. Sorensen, Kirsten Fode, Jorn Larsen, Hans von der Maase
Journal: Journal of Clinical Oncology (2006)

Purpose To evaluate the novel tumor biomarker YKL-40 in serial serum samples from patients with American Joint Committee on Cancer (AJCC) stage I and II melanoma from the time of diagnosis and during routine follow-up. Macrophages, neutrophils, and cancer cells secrete YKL-40, and a high serum level has been associated with poor prognosis in patients with several cancer types. Patients and Methods Serum samples from 234 patients with stage I (n = 162) and II (n = 72) melanoma were analyzed for YKL-40 by enzyme-linked immunosorbent assay. Serial samples were obtained before definitive primary surgery and during follow-up. Results After a median follow-up period of 66 months (range, 1 to 97 months), 41 relapses (18%) and 39 deaths (17%) were observed. Serum YKL-40 treated as an updated continuous covariate were analyzed together with the covariates sex, age, primary tumor site, ulceration, thickness, Clark level and histologic subtype in a Cox proportional hazard model. Serum YKL-40 was an independent prognostic factor of relapse-free survival (hazard ratio [HR], 1.6; 95% CI, 1.1 to 2.5; P = .03) and overall survival (HR, 1.8; 95% CI, 1.2 to 2.6; P = .002) together with thickness and ulceration. The serum level of YKL-40 (dichotomized as normal or elevated) at the time of diagnosis was also an independent prognostic factor for overall survival (HR, 3.6, 95% CI, 1.7 to 7.7; P = .001). Conclusion Serum YKL-40 may be an early biomarker of relapse and survival in patients with AJCC stage I and II melanoma. Serum YKL-40 may also be useful for patient stratification and follow-up in clinical trials. Our results need confirmation in an independent study.
Targeting HER2 for the Treatment of Breast Cancer
Authors: Mothaffar F. Rimawi, Rachel Schiff, C. Kent Osborne
Journal: Annual Review of Medicine (2015)

HER2 (ErbB2), a member of the HER family of tyrosine kinase receptors (HER1–4), is a major driver of tumor growth in 20% of breast cancers. Treatment with the anti-HER2 monoclonal antibody trastuzumab has revolutionized the outcome of patients with this aggressive breast cancer subtype, but intrinsic and acquired resistance is common. Growing understanding of the biology and complexity of the HER2 signaling network and of potential resistance mechanisms has guided the development of new HER2-targeted agents. Combinations of these drugs to more completely inhibit the HER receptor layer, or combining HER2-targeted agents with agents that target downstream signaling, alternative pathways, or components of the host immune system, are being vigorously investigated in the preclinical and clinical settings. As a result, the list of more effective and well tolerated FDA-approved new regimens for patients with HER2+ tumors is constantly growing.
Follicular psoriasis: an under-reported entity. A report of five cases
Authors: T. PLOYSANGAM, D.F. MUTASIM
Journal: British Journal of Dermatology (1997)

Follicular psoriasis is not rare in dermatological practice, although only a few cases have been reported. We describe five patients with follicular psoriasis, one man and four women. The patients ranged in age from 23 to 73 years. Lesions consisted of erythematous scaly follicular papules located on the trunk and extremities. Two patients had associated plaque-type psoriasis of the scalp. None had nail involvement at the time of diagnosis. Histological examination of several biopsy specimens revealed the changes of psoriasis in the follicular epithelium.
Detection of TMPRSS2-ERG Fusion Transcripts and Prostate Cancer Antigen 3 in Urinary Sediments May Improve Diagnosis of Prostate Cancer
Authors: Daphne Hessels, Frank P. Smit, Gerald W. Verhaegh, J. Alfred Witjes, Erik B. Cornel, Jack A. Schalken
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Early detection of prostate cancer can increase the curative success rate for prostate cancer. We studied the diagnostic usefulness of TMPRSS2-ERG fusion transcripts as well as the combination of prostate cancer antigen 3 (PCA3) RNA and TMPRSS2-ERG fusion transcripts in urinary sediments after digital rectal examination (DRE). Experimental Design: A total of 78 men with prostate cancer–positive biopsies and 30 men with prostate cancer–negative biopsies were included in this study. After DRE, the first voided urine was collected, and urinary sediments were obtained. We used semiquantitative reverse transcription-PCR (RT-PCR) analysis followed by Southern blot hybridization with a radiolabeled probe for the detection TMPRSS2-ERG fusion transcripts in these urinary sediments. A quantitative RT-PCR assay for PCA3 was used to determine the PCA3 score in the same sediments. Results: TMPRSS2-ERG fusion transcripts can be detected in the urine after DRE with a sensitivity of 37%. In this cohort of patients, the PCA3-based assay had a sensitivity of 62%. When both markers were combined, the sensitivity increased to 73%. Especially in the cohort of men with persistently elevated serum prostate-specific antigen levels and history of negative biopsies, the high positive predictive value of 94% of TMPRSS2-ERG fusion transcripts could give a better indication which patients require repeat biopsies. Conclusion: In this report, we used for the first time the combination of the prostate cancer–specific biomarkers TMPRSS2-ERG and PCA3, which significantly improves the sensitivity for prostate cancer diagnosis.
Cross sectional study of social variation in use of an out of hours patient transport service
Authors: C. A O'Donnell, A. McConnachie, K. Moffat, N. Drummond, P. Wilson, S. Ross
Journal: BMJ (1999)

Out of hours primary care has undergone radical reorganisation in recent years, with increasing numbers of general practitioner cooperatives operating from primary care emergency centres.1 A major issue continues to be equity of access, particularly in areas of socioeconomic deprivation where demand is high but access to transport is poor. 2 3 In Glasgow, 52% of the population reside in areas of deprivation (Carstairs and Morris deprivation categories 6or 7).4

The Glasgow Emergency Medical Service was established in February 1996: it covers around 950000patients and 95% of the city's 219general practices, and operates from six centres across the city. The service offers free transport for patients between their homes and the centres.

We collected data on all patient contacts with the emergency service over one week in October 1996(n=3193). The socioeconomic category of the patients was derived from their postcode sector of residence (depcats 1and 2,affluent; 3-5,intermediate; 6 and 7,deprived).4 Time of first contact with the service was categorised as evening …
Granulocyte‐macrophage colony stimulating factor for the treatment of drug induced agranulocytosis
Authors: Sucha Nand, Robert Bayer, Richard A. Prim, William Felten, John E. Godwin
Journal: American Journal of Hematology (1991)

Abstract Drug induced agranulocytosis is an uncommon but potentially fatal complication. In some cases, it may be associated with hypoplasia and depletion of granulocytic precursors in the marrow, leading to prolonged neutropenia. We report on the use of granulocytic‐macrophage colony stimulating factor (GM‐CSF) in two such cases, at a dose of 10 μg per kilogram per day subcutaneously. The absolute neutrophil count rose above 500/mm 3 in 3 days in both cases. We believe that GM‐CSF expedited the recovery of granulocyte counts in our patients and warrants further study in the management of drug induced neutropenia.
NEMO Prevents Steatohepatitis and Hepatocellular Carcinoma by Inhibiting RIPK1 Kinase Activity-Mediated Hepatocyte Apoptosis
Authors: Vangelis Kondylis, Apostolos Polykratis, Hanno Ehlken, Laura Ochoa-Callejero, Beate Katharina Straub, Santosh Krishna-Subramanian, Trieu-My Van, Harald-Morten Curth, Nicole Heise, Falk Weih, Ulf Klein, Peter Schirmacher, Michelle Kelliher, Manolis Pasparakis
Journal: Cancer Cell (2015)

IκB kinase/nuclear factor κB (IKK/NF-κB) signaling exhibits important yet opposing functions in hepatocarcinogenesis. Mice lacking NEMO in liver parenchymal cells (LPC) spontaneously develop steatohepatitis and hepatocellular carcinoma (HCC) suggesting that NF-κB prevents liver disease and cancer. Here, we show that complete NF-κB inhibition by combined LPC-specific ablation of RelA, c-Rel, and RelB did not phenocopy NEMO deficiency, but constitutively active IKK2-mediated NF-κB activation prevented hepatocellular damage and HCC in NEMOLPC-KO mice. Knock-in expression of kinase inactive receptor-interacting protein kinase 1 (RIPK1) prevented hepatocyte apoptosis and HCC, while RIPK1 ablation induced TNFR1-associated death domain protein (TRADD)-dependent hepatocyte apoptosis and liver tumors in NEMOLPC-KO mice, revealing distinct kinase-dependent and scaffolding functions of RIPK1. Collectively, these results show that NEMO prevents hepatocarcinogenesis by inhibiting RIPK1 kinase activity-driven hepatocyte apoptosis through NF-κB-dependent and -independent functions.
Chemotherapy in advanced gastric cancer: a controlled, prospective, randomised multi-centre study.
Authors: M O Rake, C N Mallinson, J B Cocking, M T Cwynarski, C A Fox, V J Wass, B L Diffey, G A Jackson
Journal: Gut (1979)

Seventy-six patients with advanced gastric adenocarcinoma were studied in a prospecitive, randmoised, controlled trial using vincristine, methotrexate, cyclophosphamide, and 5-fluorouracil in an initiation course and mitomycin-C with 5-fluorouracil as maintenance therapy. Thirty-seven patients were inoperable and 39 had the primary tumour resected with histological evidence of residual disease. Survival in the inoperable group was short and showed no significant difference between treated and control patients. The median survival times for treated and control groups were 9.5 and 9.0 weeks respectively. In the resected patients there was no difference in ultimate overall survival between the groups but up to 20 weeks there was a suggestion that the probability of survival in treated patients was higher (P = 0.06). The patients were well-matched and it is concluded that chemotherapy has had an early effect but that a further trial with more detailed stratification, particularly of staging and histological grade, is needed. No patient received treatment for longer than two years and unacceptable toxicity occurred in only two patients. Nausea occurred more frequently in the treated group but was short-lived and clinically manageable.
Epidermal growth factor receptor variant type III markedly accelerates angiogenesis and tumor growth via inducing c-myc mediated angiopoietin-like 4 expression in malignant glioma
Authors: Yasufumi Katanasaka, Yasuo Kodera, Yuka Kitamura, Tatsuya Morimoto, Tomohide Tamura, Fumiaki Koizumi
Journal: Molecular Cancer (2013)

Abstract Background Expression of the constitutively activated mutant EGFR variant III (EGFRvIII), the most common mutation in glioblastoma multiforme (GBMs), has been clinically correlated with tumor proliferation, invasion, and angiogenesis. In this study, we examined the role of EGFRvIII on the tumor microenvironment, especially on angiogenesis. Methods To study the role of EGFRvIII in tumor angiogenesis, we prepared LN229 glioblastoma transfected with enhanced green fluorescent protein (EGFP), wild-type EGFR, or EGFRvIII (LN229-WT or -vIII), and examined tumor growth and microvessel density in the tumors. Additionally, the potential angiogenic factors were identified by real-time PCR analysis, and the functions in LN229-vIII cells were examined. Results LN229-vIII cells showed more aggressive tumor growth and higher vascularity as compared to LN229-WT cells in vivo, although there was no significant difference in the cell growth rates in vitro. We next investigated the expression of 60 angiogenesis-related factors to clarify the mechanisms underlying the difference in vascularity between tumor xenografts of LN229-vIII and LN229-WT. We found that the mRNA and protein expressions of angiopoietin-like 4 (Angptl4), a secreted protein involved in angiogenesis and metabolism regulation, were significantly induced by EGFRvIII overexpression, both in vitro and in vivo. Constitutive knockdown of Angptl4 in LN229-vIII using shRNA significantly decreased the microvessel density in the tumor xenografts and suppressed tumor growth. To clarify the regulatory mechanisms of Angptl4 by EGFRvIII, we analyzed the signaling pathways and transcription factors by pharmacological inhibition and RNA interference. U0126, an ERK signal inhibitor dramatically suppressed Angptl4 expression. The transcription factor c-Myc, which is regulated by ERK, was activated in the LN229-vIII cells and knockdown of c-Myc using siRNA also attenuated Angptl4 expression in the LN229-vIII cells. Furthermore, chromatin immunoprecipitation (ChIP) assay revealed increased recruitment of c-Myc to the promoter region of Angptl4 in the LN229-vIII cells. Conclusions In summary, we demonstrated that EGFRvIII induces Angptl4 expression through the ERK/c-Myc pathway and promotes tumor angiogenesis in malignant gliomas.
Apneic oxygenation via nasal prongs at 10 L/min prevents hypoxemia during tracheal intubation for elective surgery
Authors: Chris Christodoulou, Pam Rohald, Tim Mullen, Tony Tran, Brett Hiebert, Trevor Lee, Sat Sharma
Journal: European Respiratory Journal (2013)

Introduction:  Hypoxemia during airway management remains an important cause of morbidity and mortality. Oxygenation during intubation via nasal prongs may prevent critical desaturations (Anesthesiology 1988, J Korean Med Sci 1998). We evaluated the effectiveness of oxygen administration via nasal prongs during apneic period following induction of general anesthesia.   Methods:  We conducted a randomized, controlled, double-blind study in patients without significant cardiac or respiratory disease undergoing elective surgery (age 18-65, ASA I-III). Patients randomly received oxygen via nasal prongs at 0, 5, or 10 L/min. Following preoxygenation, general anesthesia was induced. At 90 seconds after induction, nasal prongs were applied and oxygen was delivered according to the experimental group. At 4.5 minutes post-induction the patients were intubated.   Results:  The study population consisted of 41 individuals, 14 in the 0 L group, 13 in the 5 L group, and 14 in the 10 L group. Significant difference occurred between the three treatments (p=0.030), across time (p=0.028), and the treatment effect across time (p=0.017). Mean PaO 2  was higher in the 10 L group than the 5 L group (p=0.001) and 0 L group at 4 minutes (p=0.004).   Conclusion:  Apneic oxygenation with 10 L/min compared to 5 L/min via nasal prongs demonstrated delay of desaturation and maintenance of higher PaO 2  levels during elective intubation.
Excess hospitalisation burden associated with Clostridium difficile in patients with inflammatory bowel disease
Authors: A N Ananthakrishnan, E L McGinley, D G Binion
Journal: Gut (2007)

<h3>Background:</h3> <i>Clostridium difficile</i> is an important cause of diarrhoea in hospitalised patients. An increasing number of cases of <i>C difficile</i> colitis occur in patients with inflammatory bowel disease (IBD)—Crohn's disease (CD), ulcerative colitis (UC). <h3>Objective:</h3> To estimate the potential excess morbidity and mortality associated with <i>C difficile</i> in hospitalised patients with IBD. <h3>Methods:</h3> Data from the Nationwide Inpatient Sample (2003) were analysed and outcomes were examined of patients hospitalised with both <i>C difficile</i> colitis and IBD compared with those hospitalised for either condition alone. The primary outcome was in-hospital mortality. A subgroup analysis was also performed comparing outcomes of <i>C difficile</i> infection in patients with CD and UC. <h3>Results:</h3> 2804 discharges were diagnosed as having both <i>C difficile</i> and IBD, 44 400 as having <i>C difficile</i> alone, and 77 366 as having IBD alone. On multivariate analysis, patients in the <i>C difficile</i>–IBD group had a four times greater mortality than patients admitted to hospital for IBD alone (aOR = 4.7, 95% CI 2.9 to 7.9) or <i>C difficile</i> alone (aOR = 2.2, 95% CI 1.4 to 3.4), and stayed in the hospital for three days longer (95% CI 2.3 to 3.7 days). Significantly higher mortality, endoscopy and surgery rates were found in patients with UC compared with CD (p&lt;0.05), but no significant difference in length of stay or median hospital charge between the two groups was seen. <h3>Conclusions:</h3> <i>C difficile</i> colitis is associated with a significant healthcare burden in hospitalised patients with IBD and carries a higher mortality than in patients with <i>C difficile</i> without underlying IBD.
Effect of changes over time in the performance of a customized SAPS-II model on the quality of care assessment
Authors: Lilian Minne, Saeid Eslami, Nicolette de Keizer, Evert de Jonge, Sophia E. de Rooij, Ameen Abu-Hanna
Journal: Intensive Care Medicine (2011)

The aim of our study was to explore, using an innovative method, the effect of temporal changes in the mortality prediction performance of an existing model on the quality of care assessment. The prognostic model (rSAPS-II) was a recalibrated Simplified Acute Physiology Score-II model developed for very elderly Intensive Care Unit (ICU) patients.The study population comprised all 12,143 consecutive patients aged 80 years and older admitted between January 2004 and July 2009 to one of the ICUs of 21 Dutch hospitals. The prospective dataset was split into 30 equally sized consecutive subsets. Per subset, we measured the model's discrimination [area under the curve (AUC)], accuracy (Brier score), and standardized mortality ratio (SMR), both without and after repeated recalibration. All performance measures were considered to be stable if <2 consecutive points fell outside the green zone [mean ± 2 standard deviation (SD)] and none fell outside the yellow zone (mean ± 4SD) of pre-control charts. We compared proportions of hospitals with SMR>1 without and after repeated recalibration for the year 2009.For all subsets, the AUCs were stable, but the Brier scores and SMRs were not. The SMR was downtrending, achieving levels significantly below 1. Repeated recalibration rendered it stable again. The proportions of hospitals with SMR>1 and SMR<1 changed from 15 versus 85% to 35 versus 65%.Variability over time may markedly vary among different performance measures, and infrequent model recalibration can result in improper assessment of the quality of care in many hospitals. We stress the importance of the timely recalibration and repeated validation of prognostic models over time.
Impaired Glucose Tolerance of Pregnancy Is a Heterogeneous Metabolic Disorder as Defined by the Glycemic Response to the Oral Glucose Tolerance Test
Authors: Ravi Retnakaran, Bernard Zinman, Philip W. Connelly, Mathew Sermer, Anthony J.G. Hanley
Journal: Diabetes Care (2006)

OBJECTIVE—Gestational diabetes mellitus (GDM), defined by two abnormal glucose values on a 3-h oral glucose tolerance test (OGTT), is associated with insulin resistance and a low serum concentration of adiponectin. The metabolic implications of impaired glucose tolerance (IGT) of pregnancy (i.e., a single abnormal value on an OGTT), however, are not well established. We sought to evaluate the metabolic phenotype of pregnant women with IGT in relation to the timing of their isolated hyperglycemia. RESEARCH DESIGN AND METHODS—A cross-sectional study was performed in pregnant women undergoing a 3-h, 100-g OGTT. The OGTT stratified participants into four groups: 1) GDM (n = 48), 2) 1-h IGT (single elevated value at 1 h) (n = 15), 3) 2-h/3-h IGT (single elevated value at either 2 or 3 h) (n = 23), and 4) normal glucose tolerance (NGT) (n = 93). Insulin sensitivity was measured by the validated insulin sensitivity index (ISOGTT) of Matsuda and DeFronzo. RESULTS—Measures of severity of glycemia (fasting glucose, area under the glucose curve from the OGTT, and glucose challenge test result) were highest in the GDM group, followed by the 1-h IGT, 2-h/3-h IGT, and NGT groups, respectively (each trend P &amp;lt; 0.0001). Consistent with this finding, ISOGTT was highest in the NGT group (5.1), followed by the 2-h/3-h IGT (4.6), 1-h IGT (3.8), and GDM (3.2) groups (trend P &amp;lt; 0.0001). Furthermore, on multiple linear regression analysis of ISOGTT, both GDM and 1-h IGT were independently associated with reduced insulin sensitivity (whereas 2-h/3-h IGT was not). Mean adjusted adiponectin was highest in the NGT group (15.7 μg/ml), followed by the 2-h/3-h IGT (15.6 μg/ml), 1-h IGT (13.7 μg/ml), and GDM (12.0 μg/ml) groups (trend P = 0.0024). CONCLUSIONS—The metabolic implications of IGT in pregnancy vary in relation to the timing of the abnormal glucose value from the diagnostic OGTT. The metabolic phenotype associated with 1-h IGT resembles that of GDM, whereas the phenotype associated with 2-h/3-h IGT exhibits similarity to that of NGT.