tbuckley/cabot-search huggingface dataset:
Fatal Ventricular Fibrillation Following Intravenous Sodium Diphenylhydantoin Therapy
Authors: G. Lee Gellerman
Journal: JAMA (1967)

IN RECENT YEARS there has been an increase in the use of sodium diphenylhydantoin (Dilantin) for the treatment of cardiac arrhythmias. Among the main advantages for the use of diphenylhydantoin are its ready accessibility, relative safety, and the speed with which an effect is noted. Several papers regarding its indications and complications have been published. This report describes a complication not previously recorded of diphenylhydantoin used intravenously in the treatment of cardiac arrhythmias. <h3>Report of a Case</h3> An 85-year-old Negro woman was admitted to the hospital with a one-week history of progressive shortness of breath associated with a cough which produced white sputum. There was no hemoptysis or chest pain. Physical examination revealed a well developed, elderly Negro woman who was semiconscious and who responded poorly to verbal stimuli. She had obvious respiratory distress. Her pulse rate was 104 beats per minute and regular with a blood pressure of 140/80
Maintenance of Head and Neck Tumor Gene Expression Profiles upon Lymph Node Metastasis
Authors: Paul Roepman, Alike de Jager, Marian J.A. Groot Koerkamp, J. Alain Kummer, Piet J. Slootweg, Frank C.P. Holstege
Journal: Cancer Research (2006)

Spread of cancer and development of solid metastases at distant sites is the main cause of cancer-related deaths. To understand and treat metastases, it is important to determine at which stages the most pivotal steps for development of metastases occur. In head and neck squamous cell carcinoma (HNSCC), metastasis nearly always occurs first in local lymph nodes before development of distant metastasis. Here, we have investigated gene expression patterns in HNSCC lymph node metastases using DNA microarrays. Several types of analyses show that the gene expression patterns in lymph node metastases are most similar to the corresponding primary tumors from which they arose, as long as samples contain sufficient proportions of tumor cells. Strikingly, gene expression patterns of metastatic primary HNSCC are largely maintained upon spread to the lymph node. Only a single gene, metastasis-associated gene 1 (MTA1), was found to show consistently changed expression between a large number of matched primary tumor-lymph node metastasis pairs. The maintained expression pattern includes the predictive signature for HNSCC lymph node metastasis. These results underscore the importance of the primary tumor gene expression profile for development and treatment of metastasis. The findings also agree with the concept that disseminated cancer cells alter the surrounding tissue into a metastatic environment that resembles the primary tumor microenvironment.
Cingulate Epilepsy
Authors: Rafeed Alkawadri, Norman K So, Paul C Van Ness, Andreas V Alexopoulos
Journal: JAMA Neurology (2013)

The literature on cingulate gyrus epilepsy in the magnetic resonance imaging era is limited to case reports and small case series. To our knowledge, this is the largest study of surgically confirmed epilepsy arising from the anterior or posterior cingulate region.To characterize the clinical and electrophysiological findings of epilepsies arising from the anterior and posterior cingulate gyrus.We studied consecutive cingulate gyrus epilepsy cases identified retrospectively from the Cleveland Clinic and University of Texas Southwestern Medical Center epilepsy databases from 1992 to 2009. Participants included 14 consecutive cases of cingulate gyrus epilepsies confirmed by restricted magnetic resonance image lesions and seizure freedom or marked improvement following lesionectomy.The main outcome measure was improvement in seizure frequency following surgery. The clinical, video electroencephalography, neuroimaging, pathology, and surgical outcome data were reviewed.All 14 patients had cingulate epilepsy confirmed by restricted magnetic resonance image lesions and seizure freedom or marked improvement following lesionectomy. They were divided into 3 groups based on anatomical location of the lesion and corresponding seizure semiology. In the posterior cingulate group, all 4 patients had electroclinical findings suggestive of temporal origin of the epilepsy. The anterior cingulate cases were divided into a typical (Bancaud) group (6 cases with hypermotor seizures and infrequent generalization with the presence of fear, laughter, or severe interictal personality changes) and an atypical group (4 cases presenting with simple motor seizures and a tendency for more frequent generalization and less-favorable long-term surgical outcome). All atypical cases were associated with an underlying infiltrative astrocytoma.Posterior cingulate gyrus epilepsy may present with electroclinical findings that are suggestive of temporal lobe epilepsy and can be considered as another example of pseudotemporal epilepsies. The electroclinical presentation and surgical outcome of lesional anterior cingulate epilepsy is possibly influenced by the underlying pathology. This study highlights the difficulty in localizing seizures arising from the cingulate gyrus in the absence of a magnetic resonance image lesion.
Perforin activates clathrin- and dynamin-dependent endocytosis, which is required for plasma membrane repair and delivery of granzyme B for granzyme-mediated apoptosis
Authors: Jerome Thiery, Dennis Keefe, Saviz Saffarian, Denis Martinvalet, Michael Walch, Emmanuel Boucrot, Tomas Kirchhausen, Judy Lieberman
Journal: Blood (2009)
Identification of PI3K regulatory subunit p55γ as a novel inhibitor of vascular smooth muscle cell proliferation and neointimal formation
Authors: Geng Li, Ning Xie, Yuan Yao, Yan Zhang, Jiaojiao Guo, Yuanqing Feng, Fengxiang Lv, Rui-Ping Xiao, Chun-Mei Cao
Journal: Cardiovascular Research (2014)

Phosphatidylinositol 3 kinases (PI3Ks) play a pivotal role in vascular physiology and pathophysiology. We aimed to investigate the role of p55γ, a regulatory subunit of PI3Ks, in vascular smooth muscle cell (VSMC) proliferation and neointimal formation. We identified p55γ as an important factor that suppresses VSMC proliferation and injury-evoked neointimal formation. Western blot and mRNA analyses showed that p55γ expression declined in balloon-injured rat carotid arteries and in response to PDGF-BB and serum treatment in cultured VSMCs. Overexpression of p55γ inhibited, whereas short hairpin RNA knockdown of p55γ promoted PDGF-BB- and serum-induced VSMC proliferation. Importantly, in vivo adenoviral gene transfer of p55γ into carotid arteries attenuated, while knockdown of p55γ enhanced balloon injury-induced neointimal formation. Furthermore, p55γ sequentially up-regulated p53 and p21, resulting in cell-cycle arrest in S phase; small-interfering RNA knockdown of either p53 or p21 blocked p55γ-induced VSMC growth arrest. Mechanistically, p55γ interacted with and stabilized p53 protein by blocking mouse double minute 2 homologue-mediated p53 ubiquitination and degradation, subsequently activating its target gene p21. Concurrently, p55γ up-regulated Bcl-xl expression, resulting in non-apoptotic growth arrest effect. These findings mark p55γ as a novel upstream regulator of the p53-p21 signalling pathway that negatively regulates VSMC proliferation, suggesting that malfunction of p55γ may trigger vascular proliferative disorders.
The Southampton examination schedule for the diagnosis of musculoskeletal disorders of the upper limb
Authors: K. Palmer
Journal: Annals of the Rheumatic Diseases (2000)

<h3>OBJECTIVES</h3> Following a consensus statement from a multidisciplinary UK workshop, a structured examination schedule was developed for the diagnosis and classification of musculoskeletal disorders of the upper limb. The aim of this study was to test the repeatability and the validity of the newly developed schedule in a hospital setting. <h3>METHOD</h3> 43 consecutive referrals to a soft tissue rheumatism clinic (group 1) and 45 subjects with one of a list of specific upper limb disorders (including shoulder capsulitis, rotator cuff tendinitis, lateral epicondylitis and tenosynovitis) (group 2), were recruited from hospital rheumatology and orthopaedic outpatient clinics. All 88 subjects were examined by a research nurse (blinded to diagnosis), and everyone from group 1 was independently examined by a rheumatologist. Between observer agreement was assessed among subjects from group 1 by calculating Cohen9s κ for dichotomous physical signs, and mean differences with limits of agreement for measured ranges of joint movement. To assess the validity of the examination, a pre-defined algorithm was applied to the nurse9s examination findings in patients from both groups, and the sensitivity and specificity of the derived diagnoses were determined in comparison with the clinic9s independent diagnosis as the reference standard. <h3>RESULTS</h3> The between observer repeatability of physical signs varied from good to excellent, with κ coefficients of 0.66 to 1.00 for most categorical observations, and mean absolute differences of 1.4°–11.9° for measurements of shoulder movement. The sensitivity of the schedule in comparison with the reference standard varied between diagnoses from 58%–100%, while the specificities ranged from 84%–100%. The nurse and the clinic physician generally agreed in their diagnoses, but in the presence of shoulder capsulitis the nurse usually also diagnosed shoulder tendinitis, whereas the clinic physician did not. <h3>CONCLUSION</h3> The new examination protocol is repeatable and gives acceptable diagnostic accuracy in a hospital setting. Examination can feasibly be delegated to a trained nurse, and the protocol has the benefit of face and construct validity as well as consensus backing. Its performance in the community, where disease is less clear cut, merits separate evaluation, and further refinement is needed to discriminate between discrete pathologies at the shoulder.
Neutrophil gelatinase-associated lipocalin is elevated in bile from patients with malignant pancreatobiliary disease
Authors: A. Zabron, V. H.-v. d. Sluis, C. Wadsworth, M. Gierula, A. Thillainayagam, P. Vlavianos, D. Westaby, S. Taylor-Robinson, R. Edwards, S. Khan
Journal: Gut (2011)

<h3>Introduction</h3> Pancreatobiliary malignancies are amongst the commonest causes of cancer-related death worldwide and usually present with biliary obstruction. Accurate differentiation between benign and malignant causes of obstruction is likely to improve outcome in pancreatobiliary disease and reliable biomarkers are urgently needed. Bile is a potential source of such biomarkers due to its anatomical proximity to the site of pathology. Our aim was to apply a proteomic approach to identify potential biomarkers in bile which could differentiate between malignant and benign disease. <h3>Methods</h3> Bile, urine and serum were collected prospectively from 59 patients undergoing ERCP (endoscopic retrograde cholangiopancreatography) for benign (n = 36) or malignant (n = 23) pancreatobiliary disease at our centre. Initially, label-free proteomics and immunoblotting were performed in a sub-set of patients. Candidate biomarkers were selected on the basis of increased abundance of peptide fragments, and immunoblotting performed on an expanded cohort. ELISA was then performed for our potential biomarker on all samples in bile, blood and urine. <h3>Results</h3> Neutrophil gelatinase associated lipocalin (NGAL) levels were significantly raised in bile from the malignant disease group, compared to bile from the benign disease group (median 1839 ng/mL vs 472 ng/mL, p &lt; 0.001). Biliary NGAL levels had an ROC-AUC of 0.76, specificity 56% and sensitivity 96% for distinguishing malignant from benign causes. Biliary NGAL was independent of serum biochemistry and CA 19-9 in differentiating between underlying benign and malignant disease. NGAL levels were then analysed in other body fluids in the same cohort. No significant differences in serum and urine NGAL levels were found between benign and malignant disease. Combining biliary NGAL and serum CA 19-9 improved diagnostic accuracy for malignancy (sensitivity 85%, specificity 82%, positive predictive value 79%, and negative predictive value 87%). <h3>Conclusion</h3> NGAL in bile is a novel potential biomarker to distinguish benign from malignant biliary obstruction, particularly in combination with serum tumour markers.
Mortality among patients with pleural effusion undergoing thoracentesis
Authors: Erin M. DeBiasi, Margaret A. Pisani, Terrence E. Murphy, Katy Araujo, Anna Kookoolis, A. Christine Argento, Jonathan Puchalski
Journal: European Respiratory Journal (2015)

Of the 1.5 million people diagnosed with pleural effusion in the USA annually, ∼178 000 undergo thoracentesis. While it is known that malignant pleural effusion portends a poor prognosis, mortality of patients with nonmalignant effusions has not been well studied. This prospective cohort study evaluated 308 patients undergoing thoracentesis. Chart review was performed to obtain baseline characteristics. The aetiology of the effusions was determined using standardised criteria. Mortality was determined at 30 days and 1 year. 247 unilateral and 61 bilateral thoracenteses were performed. Malignant effusion had the highest 30-day (37%) and 1-year (77%) mortality. There was substantial patient 30-day and 1-year mortality with effusions due to multiple benign aetiologies (29% and 55%), congestive heart failure (22% and 53%), and renal failure (14% and 57%, respectively). Patients with bilateral, relative to unilateral, pleural effusion were associated with higher risk of death at 30 days and 1 year (17% versus 47% (hazard ratio (HR) 2.58, 95% CI 1.44–4.63) and 36% versus 69% (HR 2.32, 95% CI 1.55–3.48), respectively). Patients undergoing thoracentesis for pleural effusion have high short- and long-term mortality. Patients with malignant effusion had the highest mortality followed by multiple benign aetiologies, congestive heart failure and renal failure. Bilateral pleural effusion is distinctly associated with high mortality.
Simeprevir plus sofosbuvir, with or without ribavirin, to treat chronic infection with hepatitis C virus genotype 1 in non-responders to pegylated interferon and ribavirin and treatment-naive patients: the COSMOS randomised study
Authors: Eric Lawitz, Mark S Sulkowski, Reem Ghalib, Maribel Rodriguez-Torres, Zobair M Younossi, Ana Corregidor, Edwin DeJesus, Brian Pearlman, Mordechai Rabinovitz, Norman Gitlin, Joseph K Lim, Paul J Pockros, John D Scott, Bart Fevery, Tom Lambrecht, Sivi Ouwerkerk-Mahadevan, Katleen Callewaert, William T Symonds, Gaston Picchio, Karen L Lindsay, Maria Beumont, Ira M Jacobson
Journal: The Lancet (2014)
Evidence of genotypic diversity among Candida auris isolates by multilocus sequence typing, matrix-assisted laser desorption ionization time-of-flight mass spectrometry and amplified fragment length polymorphism
Authors: A. Prakash, C. Sharma, A. Singh, P. Kumar Singh, A. Kumar, F. Hagen, N.P. Govender, A.L. Colombo, J.F. Meis, A. Chowdhary
Journal: Clinical Microbiology and Infection (2015)
Pathological Mechanisms of Fatal Late Coronary Stent Thrombosis in Humans
Authors: Andrew Farb, Allen P. Burke, Frank D. Kolodgie, Renu Virmani
Journal: Circulation (2003)

Coronary stent deployment is associated with a low incidence of acute thrombosis. However, late stent thrombosis (LST) has likely been underrecognized clinically, and pathological descriptions are lacking.LST was defined as an acute thrombus within a stent that had been in place > or =30 days. Cases of LST were selected from a registry of human coronary stents submitted for analysis. Thirteen cases of LST (9 men, 4 women) were identified. The mean duration from implantation to thrombosis was 3.6+/-3.5 months (range, 1 to 11.9 months). The causes of death were sudden cardiac death (n=10), acute myocardial infarction (n=2), and heart failure (n=1). The pathological mechanisms of LST were as follows: (1) stenting across ostia of major arterial branches (5 cases); (2) exposure to radiation therapy (3 cases); (3) plaque disruption in the nonstented arterial segment within 2 mm of the stent margin (2 cases); (4) stenting of markedly necrotic, lipid-rich plaques with extensive plaque prolapse (2 cases); and (5) diffuse in-stent restenosis (1 case). Twelve cases demonstrated a failure to form a completely healed neointimal layer overlying stent struts. Underlying in-stent restenosis was present in only 4 (31%) of 13 cases.LST is a potentially fatal complication of coronary stenting. Stenting across branch ostia, disruption of adjacent vulnerable plaques, radiation therapy, and extensive plaque prolapse can precipitate LST. Impaired intimal healing (ie, the failure to form a complete neointimal layer over stent struts) extends the window during which stents are prone to thrombosis.
T cell–derived inducible nitric oxide synthase switches off TH17 cell differentiation
Authors: Jianjun Yang, Ruihua Zhang, Geming Lu, Yu Shen, Liang Peng, Chen Zhu, Miao Cui, Weidong Wang, Paul Arnaboldi, Meng Tang, Monica Gupta, Chen-Feng Qi, Padmini Jayaraman, Hongfa Zhu, Bo Jiang, Shu-hsia Chen, John Cijiang He, Adrian T. Ting, Ming-Ming Zhou, Vijay K. Kuchroo, Herbert C. Morse, Keiko Ozato, Andrew G. Sikora, Huabao Xiong
Journal: The Journal of Experimental Medicine (2013)

RORγt is necessary for the generation of TH17 cells but the molecular mechanisms for the regulation of TH17 cells are still not fully understood. We show that activation of CD4+ T cells results in the expression of inducible nitric oxide synthase (iNOS). iNOS-deficient mice displayed enhanced TH17 cell differentiation but without major effects on either TH1 or TH2 cell lineages, whereas endothelial NOS (eNOS) or neuronal NOS (nNOS) mutant mice showed comparable TH17 cell differentiation compared with wild-type control mice. The addition of N6-(1-iminoethyl)-l-lysine dihydrochloride (L-NIL), the iNOS inhibitor, significantly enhanced TH17 cell differentiation, and S-nitroso-N-acetylpenicillamine (SNAP), the NO donor, dose-dependently reduced the percentage of IL-17–producing CD4+ T cells. NO mediates nitration of tyrosine residues in RORγt, leading to the suppression of RORγt-induced IL-17 promoter activation, indicating that NO regulates IL-17 expression at the transcriptional level. Finally, studies of an experimental model of colitis showed that iNOS deficiency results in more severe inflammation with an enhanced TH17 phenotype. These results suggest that NO derived from iNOS in activated T cells plays a negative role in the regulation of TH17 cell differentiation and highlight the importance of intrinsic programs for the control of TH17 immune responses.
Characterisation of colorectal cancers showing hypermethylation at multiple CpG islands
Authors: M van Rijnsoever
Journal: Gut (2002)

A subgroup of colorectal cancers (CRC) referred to as the CpG island methylator phenotype (CIMP+) shows simultaneous methylation of multiple CpG islands. The clinicopathological and molecular characteristics of this phenotype remain uncertain however.We analysed methylation of CpG islands in the p16 and MDR1 genes and MINT-2 clone in 275 stage II/III CRCs.Concurrent methylation of two or more CpG islands was observed in 32% of cases and was considered to represent CIMP+. These were often poorly differentiated, had less TP53 mutations, and originated frequently in the proximal or higher stage CRC compared with CIMP- tumours (p<0.05 for each). CIMP+ had no prognostic significance in stage II or stage III CRC treated by surgery alone. hMLH1 methylated tumours comprised the majority (81%) of cases with microsatellite instability, were frequently observed in older female patients, were often poorly differentiated or CIMP+, and contained wild-type K-ras (p<0.05 for each). Females who were heterozygous or homozygous for the C677T MTHFR polymorphism were at increased risk of developing CIMP+ CRC (odds ratio 2.17, 95% confidence interval 1.03-4.57; p=0.037).These observations made in a relatively large unselected series of CRC support the notion that CIMP+ characterises a subgroup of tumours with distinctive phenotypic features.
Seasonal variation in non-specific bronchial reactivity: a study of wheat workers with a history of wheat associated asthma.
Authors: M J Hensley, R Scicchitano, N A Saunders, A W Cripps, J Ruhno, D Sutherland, R L Clancy
Journal: Thorax (1988)

To investigate seasonal variation in non-specific bronchial reactivity in wheat workers, we carried out histamine inhalation tests in 29 workers (28 of them men) from a small farming community with symptoms of wheat associated asthma before, during and after the 1983-4 Australian wheat harvest season. Four were cigarette smokers, and the age range was 12-54 (mean (SD) 30 (10)) years. Twenty eight subjects were atopic (one positive skinprick test result in tests with 10 common antigens), 60% reacting to house dust mite and all to at least one of eight wheat antigens. Baseline spirometry gave normal results (mean FVC1 90% (SD 8%) predicted; FVC 91% (7%) predicted). Bronchial reactivity was tested by the method of Yan et al. The cumulative doses of histamine acid phosphate (up to 3.91 mumol) that caused a fall of 20% from baseline in FEV1 was determined (PD20) and expressed as the geometric mean. In the low exposure season, May 1983, nine subjects had a PD20 (mean 1.2, range 0.3-3.9 mumol). The number rose to 19 in the summer harvest season, December 1983 (mean 0.8, range 0.07-3.9 mumol) and returned to nine in the subsequent winter, July 1984 (mean 1.8, range 0.4-3.9 mumol). The change in the number of subjects with a PD20 was significant (p less than 0.01). Four additional subjects probably had increased bronchial reactivity in the harvest season: in two the post-saline FEV1 was too unstable to give them histamine challenge and in two the challenge was inadvertently discontinued prematurely. Baseline FEV1 and FVC fell by 8% between the first and second studies (p less than 0.001); values were intermediate in the third study (FEV1 3.74, 3.44, and 3.57; FVC 4.66, 4.28, and 4.41 litres respectively). Linear modelling analysis of log PD20, season, FEV1, FVC, age, seasonality of asthma symptoms and skin test data indicated that the harvest season was the only significant determinant of variation in log PD20. It is concluded that in these wheat workers there is a seasonal variation in bronchial reactivity that may reflect a response to allergens associated with grain.
The prevalence of reported asthma is independent of exposure in house dust mite-sensitized children
Authors: D. Vervloet, A. Dornelas de Andrade, L. Pascal, A. Lanteaume, H. Dutau, A. Armengaud, R. Sambuc, D. Charpin
Journal: European Respiratory Journal (1999)

In areas with low house dust mite (HDM) allergen exposure, both mite sensitization and asthma prevalence are low. In most other areas, HDM allergen exposure is higher than the threshold for sensitization. In this setting, is HDM allergen exposure a factor which is causally related to the development of asthma in HDM-sensitive individuals? To answer this question, the cumulative prevalence of asthma was evaluated in a group of 157 schoolchildren, aged 10 and 11 yrs, who were allergic to HDM allergen, and compared it with HDM allergen exposure and atopic status, using univariate and multivariate analysis. HDM allergen levels were measured in mattress dust using an enzyme-linked immunosorbent assay (ELISA) method. Of mattress dust samples, 94% had an HDM allergen level &gt;2 microg x g dust(-1). Atopy was evaluated by means of skin prick tests using five common allergens. Among the predictive variables studied by means of univariate analysis, only the number of positive skin tests and male sex correlated with asthma prevalence, but not HDM allergen exposure. Logistic regression analysis also demonstrated that the number of positive skin tests correlated with asthma prevalence (odds ratio (OR)=1.38, p=0.05), whereas the OR for HDM allergen exposure was 1.0. This survey suggests that, in a geographical area with high HDM allergen exposure, asthma prevalence is not linked with HDM allergen levels.