tbuckley/cabot-search huggingface dataset:
Prognostic factors for time to treatment failure and time to 12 months of remission for patients with focal epilepsy: post-hoc, subgroup analyses of data from the SANAD trial
Authors: Laura Bonnett, Catrin Tudur Smith, David Smith, Paula Williamson, David Chadwick, Anthony G Marson
Journal: The Lancet Neurology (2012)

Epilepsy is a heterogeneous disorder, with outcomes ranging from immediate remission after taking a first antiepileptic drug to frequent unremitting seizures with multiple treatment failures. Few prognostic models enable prediction of outcome; we therefore aimed to use data from the SANAD study to predict outcome overall and for patients receiving specific treatments.The SANAD study was a randomised controlled trial in which standard antiepileptic drugs were compared with new treatments. Arm A included patients for whom carbamazepine was considered the first-line treatment, most of whom were newly diagnosed with focal epilepsy. Patients were randomly assigned to receive carbamazepine, gabapentin, lamotrigine, oxcarbazepine, or topiramate. Outcomes were time to treatment failure overall, because of inadequate seizure control, and because of adverse events, and time to 12 months of remission from seizures. In this post-hoc study we used regression multivariable modelling to investigate how clinical factors affect the probability of treatment failure and the probability of achieving 12 months of remission.For time to treatment failure, we identified several significant risk factors: sex (male vs female, hazard ratio [HR] 0·86, 95% CI 0·75-0·99), treatment history (taking non-SANAD antiepileptic drugs [other than those listed above] vs treatment naive, 1·27, 1·05-1·53), age (eg, older than 71 years vs 10 years or younger, 0·68, 0·51-0·91), total number of seizures (eg, four to 11 seizures vs two or fewer, 1·08, 1·05-1·11), electroencephalogram results (epileptiform abnormality vs normal, 1·26, 1·07-1·50), seizure type (eg, secondary generalised vs simple or complex partial only, 0·78, 0·66-0·91), site of onset (not localised vs temporal lobe, 1·25, 1·06-1·47), and treatment (lamotrigine vs carbamazepine, 0·76, 0·61-0·95). Significant factors for time to 12 months of remission were sex (male vs female, 1·19, 1·05-1·35), treatment history (taking a non-SANAD antiepileptic drug vs treatment naive, 0·64, 0·52-0·78), age (eg, older than 71 years vs 10 years or younger, 1·60, 1·26-2·03), time from first seizure (60-239 months vs ≥2 months, 1·14, 1·01-1·29; >240 months vs ≤2 months, 1·39, 1·04-1·86), neurological insult (present vs absent, 0·75, 0·61-0·93), total number of seizures before randomisation (eg, four to 11 vs two or fewer, 0·87, 0·85-0·90), and treatment (gabapentin vs carbamazepine, 0·71, 0·59-0·86; topiramate vs carbamazepine, 0·81, 0·68-0·98).We present a thorough investigation of prognostic factors from a large randomised controlled trial in patients starting antiepileptic monotherapy. If validated, our models could aid in individual patient risk stratification and the design and analysis of epilepsy trials.National Institute for Health Research (UK).
Fluorescein Discoloration of Eyes, Masking Insidious Onset of Hepatitis
Authors: Lawrence S. Miller
Journal: JAMA (1974)

To the Editor.—  This case is reported to highlight the possibility that skin and mucous membrane discoloration attributed to fluorescein may in actuality be jaundice. Intravenously administered fluorescein, widely used in plastic surgery and ophthalmology as a diagnostic tool, is considered safe. Nausea and a few allergic reactions are known to occur, but no fatalities have been reported. The dye does, however, leave a greenish yellow discoloration of the eyes, skin, and mucous membrane that clears within 24 to 48 hours. The experience gained from this case suggests cautioning patients to report discoloration noticeable beyond a 48-hour limit.  Report of a Case.—  A 52-year old white diabetic man underwent a left below-knee amputation for gangrene on Nov 27, 1972. He received three units of blood during the operation. On Dec 12, 1972, he had a revision of his right below-knee stump that had been amputated eighteen months previously because of
Glucose-Mediated N-glycosylation of SCAP Is Essential for SREBP-1 Activation and Tumor Growth
Authors: Chunming Cheng, Peng Ru, Feng Geng, Junfeng Liu, Ji Young Yoo, Xiaoning Wu, Xiang Cheng, Vanessa Euthine, Peng Hu, Jeffrey Yunhua Guo, Etienne Lefai, Balveen Kaur, Axel Nohturfft, Jianjie Ma, Arnab Chakravarti, Deliang Guo
Journal: Cancer Cell (2015)
Proteomic identification of FHL1 as the protein mutated in human reducing body myopathy
Authors: Joachim Schessl, Yaqun Zou, Meagan J. McGrath, Belinda S. Cowling, Baijayanta Maiti, Steven S. Chin, Caroline Sewry, Roberta Battini, Ying Hu, Denny L. Cottle, Michael Rosenblatt, Lynn Spruce, Arupa Ganguly, Janbernd Kirschner, Alexander R. Judkins, Jeffrey A. Golden, Hans-Hilmar Goebel, Francesco Muntoni, Kevin M. Flanigan, Christina A. Mitchell, Carsten G. Bönnemann
Journal: Journal of Clinical Investigation (2008)

Reducing body myopathy (RBM) is a rare disorder causing progressive muscular weakness characterized by aggresome-like inclusions in the myofibrils. Identification of genes responsible for RBM by traditional genetic approaches has been impossible due to the frequently sporadic occurrence in affected patients and small family sizes. As an alternative approach to gene identification, we used laser microdissection of intracytoplasmic inclusions identified in patient muscle biopsies, followed by nanoflow liquid chromatography–tandem mass spectrometry and proteomic analysis. The most prominent component of the inclusions was the Xq26.3-encoded four and a half LIM domain 1 (FHL1) protein, expressed predominantly in skeletal but also in cardiac muscle. Mutational analysis identified 4 FHL1 mutations in 2 sporadic unrelated females and in 2 families with severely affected boys and less-affected mothers. Transfection of kidney COS-7 and skeletal muscle C2C12 cells with mutant FHL1 induced the formation of aggresome-like inclusions that incorporated both mutant and wild-type FHL1 and trapped other proteins in a dominant-negative manner. Thus, a novel laser microdissection/proteomics approach has helped identify both inherited and de novo mutations in FHL1, thereby defining a new X-linked protein aggregation disorder of muscle.
Klippel-Trenaunay syndrome with small vessel pulmonary arterial hypertension
Authors: S Ulrich
Journal: Thorax (2005)

A patient with Klippel-Trenaunay syndrome and pulmonary arterial hypertension not associated with chronic thrombo-embolic pulmonary hypertension is described. It is hypothesised that pulmonary arterial hypertension is another complication associated with the Klippel-Trenaunay syndrome, possibly due to haemodynamic changes of small vessel abnormalities.
Effect of the antihepcidin Spiegelmer lexaptepid on inflammation-induced decrease in serum iron in humans
Authors: Lucas T. van Eijk, Aaron S. E. John, Frank Schwoebel, Luciana Summo, Stéphanie Vauléon, Stefan Zöllner, Coby M. Laarakkers, Matthijs Kox, Johannes G. van der Hoeven, Dorine W. Swinkels, Kai Riecke, Peter Pickkers
Journal: Blood (2014)
Arteriogenesis is associated with an induction of the cardiac ankyrin repeat protein (carp)
Authors: K Boengler
Journal: Cardiovascular Research (2003)

Objective: Collateral artery growth (arteriogenesis) can be induced in rabbit and mice by occlusion of the femoral artery. We aimed to identify genes that are differentially expressed during arteriogenesis. Methods: 24 h after femoral ligation or sham operation collateral arteries were isolated from New Zealand white rabbits, mRNAs were extracted and amplified using the SMART technique. cDNAs were subjected to suppression subtractive hybridization. The differential expression was confirmed by Northern blot, Real time PCR and Western blot. Additionally, the gene expression was modulated in vivo by application of cytokines via osmotic minipumps. Results: We found the cardiac ankyrin repeat protein (carp) mRNA to be upregulated at 24 h and already at 6 h and 12 h after surgery as shown by Northern blot hybridization and real time PCR. The carp mRNA was also increased in our mouse model of arteriogenesis. Western blot results on nuclear extracts of rabbit collaterals 24 h after surgery indicated that carp, which we showed to be expressed in endothelial cells and smooth muscle cells of collateral arteries by immunohistochemistry, was also upregulated on the protein level. We infused MCP-1, TGF-β1 or doxorubicin for 24 h in rabbits and found that only TGF-β1 led to an additional increase of carp mRNA. Overexpression of carp in cos-1 cells resulted in a 3.7-fold increase of the immediate early gene egr-1. Conclusions: Our results implicate that carp is associated with the initiation and regulation of arteriogenesis.
Absence of collagen-induced platelet activation caused by compound heterozygous GPVI mutations
Authors: Bénédicte Dumont, Dominique Lasne, Chantal Rothschild, Maxime Bouabdelli, Véronique Ollivier, Claire Oudin, Nadine Ajzenberg, Bernard Grandchamp, Martine Jandrot-Perrus
Journal: Blood (2009)
Lifestyle Modification Improves Endothelial Function in Obese Subjects With the Insulin Resistance Syndrome
Authors: Osama Hamdy, Sarah Ledbury, Cathy Mullooly, Catherine Jarema, Satoko Porter, Kerry Ovalle, Amr Moussa, Antonella Caselli, A. Enrique Caballero, Panayiotis A. Economides, Aristidis Veves, Edward S. Horton
Journal: Diabetes Care (2003)

OBJECTIVE—Endothelial dysfunction has been reported in type 2 diabetic patients and in obese subjects with insulin resistance syndrome (IRS). This study evaluates the effects of weight reduction and exercise on vascular reactivity of the macro- and the microcirculation in obese subjects with IRS. RESEARCH DESIGN AND METHODS—We studied 24 obese subjects (9 men and 15 women, age 49.3 ± 1.9 years, BMI 36.7 ± 0.94 kg/m2, mean ± SEM) with IRS at baseline and after 6 months of weight reduction and exercise. Brachial artery flow-mediated dilation (FMD) and response to sublingual glyceryltrinitrate (GTN) were assessed by high-resolution ultrasound. Microvascular reactivity was evaluated by the laser-Doppler perfusion imaging after iontophoresis of acetylcholine and sodium nitroprusside. We also measured plasma levels of soluble intercellular adhesion molecule (sICAM), vascular adhesion molecule, von Willebrand factor, plasminogen activator inhibitor-1 (PAI-1) antigen, and tissue plasminogen activator antigen. RESULTS—This intervention resulted in 6.6 ± 1% reduction in body weight (P &amp;lt; 0.001) and significant improvement of insulin sensitivity index (2.9 ± 0.36 vs. 1.9 ± 0.33 [10−4 · min−1 · (μU ml−1)], P &amp;lt; 0.001). FMD significantly improved (12.9 ± 1.2% vs. 7.9 ± 1.0%, P &amp;lt; 0.001), whereas response to GTN and microvascular reactivity did not change. Similar observations were seen when the subjects were subclassified according to their glucose tolerance to normal glucose tolerance, impaired glucose tolerance, and type 2 diabetes. sICAM and PAI-1 significantly decreased (251.3 ± 7.7 vs. 265.6 ± 9.3 ng/ml, P = 0.018 and 36.2 ± 3.6 vs. 48.6 ± 3.9 ng/ml, P = 0.001, respectively). The relationship between percentage weight reduction and improved FMD was linear (R2 = 0.47, P = 0.001). CONCLUSIONS—We conclude that 6 months of weight reduction and exercise improve macrovascular endothelial function and reduces selective markers of endothelial activation and coagulation in obese subjects with IRS regardless of the degree of glucose tolerance.
Immediate access rheumatology clinic: efficiency and outcomes
Authors: Miriam Gärtner, Julia P Fabrizii, Elisabeth Koban, Martin Holbik, Lorenz P Machold, Josef S Smolen, Klaus P Machold
Journal: Annals of the Rheumatic Diseases (2011)

In order to facilitate access and shorten waiting times to rheumatologist assessment, an immediate access clinic (IAC) was established. Patients were assessed at presentation in the clinic and after 6-12 months, either in the clinic or by telephone. Data regarding diagnostic accuracy, pain levels and care were analysed.From February to December 2009, 1036 patients were assessed. 223 (21.5%) patients had symptoms for 3 months or less. 660 were available for re-assessment after 6-12 months. Initial tentative diagnoses were confirmed in over 75% of patients suspected of having rheumatoid arthritis (RA), spondylarthropathy and osteoarthritis. Men suspected of having spondylarthropathy had a significantly longer symptom duration than women (median (IQR) 54.0 (18.0-120.0) vs 24.0 (6.0-66.0) months; p=0.0082). There was no significant gender difference regarding pain. At follow-up, the visual analogue scale for pain in RA patients admitted to further care in the clinic (n=61) had significantly decreased by a median (IQR) of 37.5 mm (10.5-50.5), whereas this improvement was only 6 mm (-26-33.5) in the 22 RA patients followed outside the clinic (p=0.0083).The IAC resulted in considerable waiting time reduction for rheumatology assessment. A substantial minority was seen before 3 months' symptom duration. 'Positive predictive correctness' of the assessing rheumatologists regarding the presence of inflammatory rheumatic conditions was over 75%. Patients with RA cared for in the clinic had substantially lower pain levels after 6-12 months' follow-up than patients treated elsewhere.
Induction of tolerance in influenza virus-immune T lymphocyte clones with synthetic peptides of influenza hemagglutinin.
Authors: J R Lamb, B J Skidmore, N Green, J M Chiller, M Feldmann
Journal: The Journal of Experimental Medicine (1983)

Antigen-specific human T cell clones specific for defined peptides of influenza A hemagglutinin were found to be rendered unresponsive by incubation with moderately high concentrations of antigen. This was the case whether the synthetic peptide antigen was present for the duration of the culture or the cloned T cells were preincubated with antigen for 3-18 h at 37 degrees C, before stimulation with T-depleted irradiated sheep erythrocyte non-rosette-forming lymphocytes (E-) pulsed with the optimal dose of peptide. Tolerance could not be overcome by culture with various numbers of E- cells and antigen. The induction of unresponsiveness was antigen specific, since it depended upon incubation with the appropriate peptide recognized by that clone. In addition, the tolerant T cells remained unresponsive to stimulation with the specific peptide for at least 7 d after induction even though maintained in culture in the presence of T cell growth factor. This state of antigen-specific unresponsiveness is akin to immunological tolerance. Furthermore, the experiments reported here demonstrate that the helper T cell clone can be inhibited by the relevant peptide in the absence of any suppressor cells or their precursors. This suggests that antigen-induced unresponsiveness need not always depend on the presence of suppressor T cells. The induction of tolerance in T cell clones does not result in early T cell death, since cells that no longer proliferate in response to the specific antigen and accessory cells still proliferate in response to T cell growth factor.
Capecitabine Plus Oxaliplatin in Metastatic Colorectal Cancer
Authors: Jim Cassidy
Journal: Journal of Clinical Oncology (2007)

AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST The author(s) indicated no potential conflicts of interest. REFERENCES 1. Porschen R, Arkenau H-T, Kubicka S, et al: Phase III study of capecitabine plus oxaliplatin compared with fluorouracil and leucovorin plus oxaliplatin in metastatic colorectal cancer: A final report of the AIO colorectal study group. J Clin Oncol 25:4217-4223, 2007 2. Cassidy J, Clarke C, Diaz-Rubio E, et al: XELOX compared to FOLFOX4: Survival and response results from XELOX-1/NO16966, a randomized phase III trial of first-line treatment for patients with metastatic colorectal cancer (MCRC). J Clin Oncol 25:18s, 2007 (suppl; abstr 4030) 3. Saltz L, Clarke C, Diaz Rubio E, et al: Bevacizumab (Bev) in combination with XELOX or FOLFOX 4: Updated efficacy results from XELOX-1/NO16966, a randomized phase III trial in first-line metastatic colorectal cancer [slideset]. J Clin Oncol 25:18s, 2007 (suppl; abstr 4028)
SOCS1 Is a Suppressor of Liver Fibrosis and Hepatitis-induced Carcinogenesis
Authors: Takafumi Yoshida, Hisanobu Ogata, Masaki Kamio, Akiko Joo, Hiroshi Shiraishi, Yoko Tokunaga, Michio Sata, Hisaki Nagai, Akihiko Yoshimura
Journal: The Journal of Experimental Medicine (2004)

Hepatocellular carcinomas (HCCs) mainly develop from liver cirrhosis and severe liver fibrosis that are established with long-lasting inflammation of the liver. Silencing of the suppressor of the cytokine signaling-1 (SOCS1) gene, a negative regulator of cytokine signaling, by DNA methylation has been implicated in development or progress of HCC. However, how SOCS1 contributes to HCC is unknown. We examined SOCS1 gene methylation in &amp;gt;200 patients with chronic liver disease and found that the severity of liver fibrosis is strongly correlated with SOCS1 gene methylation. In murine liver fibrosis models using dimethylnitrosamine, mice with haploinsufficiency of the SOCS1 gene (SOCS1−/+ mice) developed more severe liver fibrosis than did wild-type littermates (SOCS1+/+ mice). Moreover, carcinogen-induced HCC development was also enhanced by heterozygous deletion of the SOCS1 gene. These findings suggest that SOCS1 contributes to protection against hepatic injury and fibrosis, and may also protect against hepatocarcinogenesis.
Integrin-mediated function of Rab GTPases in cancer progression
Authors: Dhatchayini Subramani, Suresh K Alahari
Journal: Molecular Cancer (2010)

The RAS (rat sarcoma) superfamily of small GTPases is broadly subdivided into five groups: Ras, Rho, Rab, Ran, and Arf. Rab family proteins are important in regulating signal transduction and cellular processes such as differentiation, proliferation, vesicle transport, nuclear assembly, and cytoskeleton formation. However, some Rab proteins have been reported to be necessary for the adhesion and migration of cancer cells. Although Ras and Rho family members have been strongly implicated in cancer progression, knowledge of Rabs action in this regard is limited. Some reports have also linked Rab GTPases with cancer cell migration and invasiveness. This review discusses the implications of the involvement of Rabs in malignant transformation and cancer therapy through integrin-mediated signaling events, with particular emphasis on breast cancer.
Effects of heading exposure and previous concussions on neuropsychological performance among Norwegian elite footballers
Authors: T M Straume-Naesheim, T E Andersen, J Dvorak, R Bahr
Journal: British Journal of Sports Medicine (2005)

Background: Cross-sectional studies have indicated that neurocognitive performance may be impaired among football players. Heading the ball has been suggested as the cause, but recent reviews state that the reported deficits are more likely to be the result of head injuries. Objective: To examine the association between previous concussions and heading exposure with performance on computer based neuropsychological tests among professional Norwegian football players. Methods: Players in the Norwegian professional football league (Tippeligaen) performed two consecutive baseline neuropsychological tests (Cogsport) before the 2004 season (90.3% participation, n = 271) and completed a questionnaire assessing previous concussions, match heading exposure (self-reported number of heading actions per match), player career, etc. Heading actions for 18 players observed in two to four matches were counted and correlated with their self-reported values. Results: Neither match nor lifetime heading exposure was associated with neuropsychological test performance. Nineteen players scored below the 95% confidence interval for one or more subtasks, but they did not differ from the rest regarding the number of previous concussions or lifetime or match heading exposure. The number of previous concussions was positively associated with lifetime heading exposure (exponent (B) = 1.97(1.03–3.75), p = 0.039), but there was no relation between previous concussions and test performance. Self-reported number of headings correlated well with the observed values (Spearman’s ρ = 0.77, p&lt;0.001). Conclusion: Computerised neuropsychological testing revealed no evidence of neuropsychological impairment due to heading exposure or previous concussions in a cohort of Norwegian professional football players.
A Note on the Transplantability of Organ-Cultured Normal Mouse Mammary Tissues&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Howard A. Bern, Donna Brown, Richard L. Ingraham
Journal: JNCI Journal of the National Cancer Institute (1968)

Normal prelactating mammary tissues from C3H/Crgl and A/Crgl female mice were cultured for 3, 5, or 15 days in media with no, minimal, or complete (secretion-inducing) hormone supplementation. Histological integrity proved a poor indicator of subsequent development after transplantation: Disorganized and necrotic expiants grew as well as those maintained in culture in an active secretory condition.
Prevention of asthma induced by cold air by cellulose‐fabric face mask
Authors: E. Millqvist, B. Bake, U. Bengtsson, O. Löwhagen
Journal: Allergy (1995)

We have tested the effect of a porous cellulose fabric face mask. Nine asthmatic patients, anamnestically sensitive to cold, took part in exercise tests on an ergometer bicycle at a temperature of approximately ‐10°C, with and without a face mask. For comparison, exercise tests were also performed with breathing taking place through a woolen scarf. Three minutes after finishing the exercise test, there was an average fall in FEV, of 32% in the group without a face mask. The corresponding fall in FEV, was 6% with a face mask and 17% with a scarf. In order to get some idea of the patients’ attitudes to the face mask, it was used by 25 asthma patients during a period of 2 weeks in winter, after which they were asked to answer a simple questionnaire. Eighty‐eight percent of the patients stated that the face mask had provided satisfactory protection against asthma complaints induced by cold air, and 72% reported that they had been able to spend more time out‐of‐doors. The results show that porous cellulose fabric designed as a face mask offers effective protection against asthma complaints induced by cold air and exercise, and that the patients appear to appreciate this protective aid highly despite the cosmetic disadvantages.