tbuckley/cabot-search huggingface dataset:
Hyponatraemia during terlipressin therapy
Authors: A. Krag, L. Hobolth, S. Moller, F. Bendtsen
Journal: Gut (2010)

We have read with interest the study by Lo et al 1 in a recent issue of Gut . Apart from the findings that short-term therapy with terlipressin in combination with ligation seems to improve outcome in bleeding oesophageal varices (BOVs) compared to longer treatment with terlipressin, a shorter treatment period with terlipressin most likely reduces the risk of severe side effects. Recently, a study observed that during a 5-day terlipressin treatment with 1 mg/4 h, the serum sodium decreased from 138±5 to 130±9 and in …
Multidrug resistant tuberculosis
Authors: W A GEERLIGS
Journal: Thorax (2001)

Multidrug resistant tuberculosisWe read with interest the report by White and Moore-Gillon 1 on the resource implications of multidrug resistant tuberculosis (MDR-TB) in the UK.We studied the outcome of 44 HIV negative patients with MDR-TB admitted to two tertiary care tuberculosis units in the Netherlands between 1985 and 1998. 2 3 Most (38 patients) had pulmonary tuberculosis.The mean admission period was 164 days and all patients received an individually tailored combination of antituberculosis drugs for a mean period of 608 days.We estimated the cost of treatment per patient to be US$60 000 which included admission fee, costs for outpatient visits, and the costs of drug provision.Although we did not include cost of toxicity monitoring and additional procedures, our costs compare favourably with those of White et al 1 (mean £60 000) and Mahmoudi 4 (mean US$180 000).In the Netherlands the number of patients with tuberculosis resistant to any antituberculous drugs is limited to 11%, and only 0.6% of the bacilli are MDR.Between 1993 and 1997 only 43 cases of MDR-TB were identified, of which 28% had received previous treatment for tuberculosis (Index Tuberculosis 1998, Royal Netherlands Tuberculosis Association, The Hague, 2000).This suggests that transmission of MDR bacilli rather than inadequate treatment contributes to the resistance problem in the Netherlands.In poor resource countries, directly observed short course chemotherapy of tuberculosis is generally recommended to prevent the occurrence of MDR-TB.We feel that new rapid molecular methods for detecting resistance should be developed to limit the period of potential (nosocomial and community) transmission of MDR bacilli and thus prevent the emergence of MDR-TB.Such tests should then be made available to poor resource countries at an aVordable price.
Assembling defenses against therapy-resistant leukemic stem cells: Bcl6 joins the ranks
Authors: Francesca Pellicano, Tessa L. Holyoake
Journal: The Journal of Experimental Medicine (2011)

The resistance of leukemic stem cells in response to targeted therapies such as tyrosine kinase inhibitors (TKIs) relies on the cooperative activity of multiple signaling pathways and molecules, including TGFβ, AKT, and FOXO transcription factors (TFs). B cell lymphoma 6 (BCL6) is a transcriptional repressor whose translocation or mutation is associated with diffuse large BCL. New data now show that BCL6 is critical for the maintenance of leukemias driven by the BCR-ABL translocation (Philadelphia chromosome), suggesting that BCL6 is a novel, targetable member of the complex signaling pathways critical for leukemic stem cell survival.
Global Expression Analysis of Cancer/Testis Genes in Uterine Cancers Reveals a High Incidence of <i>BORIS</i> Expression
Authors: John Ian Risinger, Gadisetti V.R. Chandramouli, G. Larry Maxwell, Mary Custer, Svetlana Pack, Dmitri Loukinov, Olga Aprelikova, Tracy Litzi, David S. Schrump, Susan K. Murphy, Andrew Berchuck, Victor Lobanenkov, J. Carl Barrett
Journal: Clinical Cancer Research (2007)

Cancer/testis (CT) genes predominantly expressed in the testis (germ cells) and generally not in other normal tissues are aberrantly expressed in human cancers. This highly restricted expression provides a unique opportunity to use these CT genes for diagnostics, immunotherapeutic, or other targeted therapies. The purpose of this study was to identify those CT genes with the greatest incidence of expression in uterine cancers.We queried the expression of known and putative CT gene transcripts (representing 79 gene loci) using whole genome gene expression arrays. Specifically, the global gene expressions of uterine cancers (n = 122) and normal uteri (n = 10) were determined using expression data from the Affymetrix HG-U133A and HG-U133B chips. Additionally, we also examined the brother of the regulator of imprinted sites (BORIS) transcript by reverse transcription-PCR and quantitative PCR because its transcript was not represented on the array.Global microarray analysis detected many CT genes expressed in various uterine cancers; however, no individual CT gene was expressed in more than 25% of all cancers. The expression of the two most commonly expressed CT genes on the arrays, MAGEA9 (24 of 122 cancers and 0 of 10 normal tissues) and Down syndrome critical region 8 (DSCR8)/MMA1 (16 if 122 cancers and 0 of 10 normal tissues), was confirmed by reverse transcription-PCR methods, validating the array screening approach. In contrast to the relatively low incidence of expression of the other CT genes, BORIS expression was detected in 73 of 95 (77%) endometrial cancers and 24 of 31 (77%) uterine mixed mesodermal tumors.These data provide the first extensive survey of multiple CT genes in uterine cancers. Importantly, we detected a high frequency of BORIS expression in uterine cancers, suggesting its potential as an immunologic or diagnostic target for these cancers. Given the high incidence of BORIS expression and its possible regulatory role, an examination of BORIS function in the etiology of these cancers is warranted.
High Frequency of Autoreactive Myelin Proteolipid Protein–Specific T Cells in the Periphery of Naive Mice
Authors: Ana C. Anderson, Lindsay B. Nicholson, Kevin L. Legge, Vadim Turchin, Habib Zaghouani, Vijay K. Kuchroo
Journal: The Journal of Experimental Medicine (2000)

The autoreactive T cells that escape central tolerance and form the peripheral self-reactive repertoire determine both susceptibility to autoimmune disease and the epitope dominance of a specific autoantigen. SJL (H-2s) mice are highly susceptible to the induction of experimental autoimmune encephalomyelitis (EAE) with myelin proteolipid protein (PLP). The two major encephalitogenic epitopes of PLP (PLP 139–151 and PLP 178–191) bind to IAs with similar affinity; however, the immune response to the PLP 139–151 epitope is always dominant. The immunodominance of the PLP 139–151 epitope in SJL mice appears to be due to the presence of expanded numbers of T cells (frequency of 1/20,000 CD4+ cells) reactive to PLP 139–151 in the peripheral repertoire of naive mice. Neither the PLP autoantigen nor infectious environmental agents appear to be responsible for this expanded repertoire, as endogenous PLP 139–151 reactivity is found in both PLP-deficient and germ-free mice. The high frequency of PLP 139–151-reactive T cells in SJL mice is partly due to lack of thymic deletion to PLP 139–151, as the DM20 isoform of PLP (which lacks residues 116–150) is more abundantly expressed in the thymus than full-length PLP. Reexpression of PLP 139–151 in the embryonic thymus results in a significant reduction of PLP 139–151-reactive precursors in naive mice. Thus, escape from central tolerance, combined with peripheral expansion by cross-reactive antigen(s), appears to be responsible for the high frequency of PLP 139–151-reactive T cells.
High Expression of the ETS Transcription Factor <i>ERG</i> Predicts Adverse Outcome in Acute T-Lymphoblastic Leukemia in Adults
Authors: Claudia D. Baldus, Thomas Burmeister, Peter Martus, Stefan Schwartz, Nicola Gökbuget, Clara D. Bloomfield, Dieter Hoelzer, Eckhard Thiel, Wolf K. Hofmann
Journal: Journal of Clinical Oncology (2006)

In adult T-lymphoblastic leukemia (T-ALL) disease-free survival remains limited to 32% to 46%. The adverse prognosis in T-ALL has not been attributed to cytogenetic or molecular aberrations. We have determined the prognostic impact of the oncogenic transcription factor ERG in T-ALL.ERG expression was analyzed by real-time polymerase chain reaction (PCR) in 105 adults with newly diagnosed T-ALL treated on the German ALL protocols. Patients were dichotomized at ERG's median expression into low (n = 52) and high (n = 53) expressers. Homeobox (HOX) 11 and HOX11L2 expression was determined by real-time PCR.High ERG expressers compared with low ERG expressers had an inferior overall survival (OS, P = .02; 5-year OS: high ERG 26% v low ERG 58%) and relapse-free survival (RFS, P = .003; 5-year RFS: high ERG 34% v low ERG 72%). On multivariable analysis high ERG expression (P = .005), immunophenotypic subgroups (early v mature v thymic T-ALL; overall P = .04), HOX11L2 positivity (P = .055), and absence of HOX11 (P = .017) were independent adverse risk factors predicting RFS. Patients with high ERG expression had a hazard ratio (HR) for relapse of 3.2. Within the good prognostic subgroup of thymic T-ALL (n = 57), high ERG (HR, 4.1; P = .02) and presence of HOX11L2 (HR, 6.6; P = .008) were independent adverse factors for RFS.High expression of ERG is an adverse risk factor in adult T-ALL. Within thymic T-ALL, otherwise classified as standard-risk, high ERG expression-identified patients that were four times more likely to fail long-term RFS. The prognostic impact of ERG may assist treatment stratification and suggest the need of alternative regimens.
Dual renin-angiotensin system blockade
Authors: P. W. de Leeuw
Journal: BMJ (2012)

Combining a renin inhibitor with an ACE inhibitor or ARB is risky

Some 30 years ago, captopril became the first angiotensin converting enzyme (ACE) inhibitor available for clinical use. Since then, several other ACE inhibitors have been introduced, as well as drugs from the angiotensin II type 1 receptor blocker (ARB) family. More recently, an orally active renin inhibitor, aliskiren, has become available. It is now possible to block renin itself, to inhibit the conversion of angiotensin I into angiotensin II, and to block the main target receptors of angiotensin II in a single patient. In the linked systematic review and meta-analysis of randomised controlled trials (doi:10.1136/bmj.e42), Harel and colleagues examined the safety of dual blockade of the renin-angiotensin system using the renin inhibitor aliskiren and an ACE inhibitor or ARB.1

Many investigators have evaluated whether delivering a combination of drugs that interfere with specific functions of the renin-angiotensin system would be more effective at reducing blood pressure or protecting target organs (or both) than giving one drug only. Both dual and triple renin-angiotensin blockade have been investigated. Most trials did not consider the potential pathophysiological consequences of blocking the system at multiple levels. A meta-analysis that compared combinations of an ACE inhibitor and ARB with single drug treatment—mainly in patients with diabetes or kidney disease—showed …
Brain imaging, ethology, and the nonhuman mind
Authors: Gordon M. Burghardt
Journal: Behavioral and Brain Sciences (1995)

Abstract Posner &amp; Raichle's (1994) exciting, wonderfully illustrated book describes the past successes and future potential of the relatively noninvasive imaging of the nervous systems of living people. The focus has been on cognitive processes but there is no reason why emotional and motivational systems cannot also be tapped. Although the authors do not formally address such contentious issues as consciousness and the private experience of other species, imaging methods may hold promise for helping us to understand these phenomena, as well as to integrate psychological processes into ethological and phylogenetic research in general.
SC-03 * NEURAL STEM CELL-MEDIATED ENZYME/PRODRUG THERAPY FOR MEDULLOBLASTOMA
Authors: M. Gutova, D. Oganesyan, S. T. Grigorova, Y. Pei, D. Shahmanyan, Z. Li, M. Barish, K. Aboody, R. Wechsler-Reya
Journal: Neuro-Oncology (2015)

Medulloblastoma is the most common malignant brain tumor in children.Despite recent advances in treatment, these tumors continue to be associated with high morbidity and mortality, and new strategies for treatment of medulloblastoma are urgently needed.Major obstacles to successful treatment of pediatric brain tumors include the blood-brain-barrier (BBB), which prevents many systemically administered anti-cancer agents from entering the central Overall survival
Identification of a panel of sensitive and specific DNA methylation markers for lung adenocarcinoma
Authors: Jeffrey A Tsou, Janice S Galler, Kimberly D Siegmund, Peter W Laird, Sally Turla, Wendy Cozen, Jeffrey A Hagen, Michael N Koss, Ite A Laird-Offringa
Journal: Molecular Cancer (2007)

Abstract Background Lung cancer is the number one cancer killer of both men and women in the United States. Three quarters of lung cancer patients are diagnosed with regionally or distantly disseminated disease; their 5-year survival is only 15%. DNA hypermethylation at promoter CpG islands shows great promise as a cancer-specific marker that would complement visual lung cancer screening tools such as spiral CT, improving early detection. In lung cancer patients, such hypermethylation is detectable in a variety of samples ranging from tumor material to blood and sputum. To date the penetrance of DNA methylation at any single locus has been too low to provide great clinical sensitivity. We used the real-time PCR-based method MethyLight to examine DNA methylation quantitatively at twenty-eight loci in 51 primary human lung adenocarcinomas, 38 adjacent non-tumor lung samples, and 11 lung samples from non-lung cancer patients. Results We identified thirteen loci showing significant differential DNA methylation levels between tumor and non-tumor lung; eight of these show highly significant hypermethylation in adenocarcinoma: CDH13, CDKN2A EX2, CDX2, HOXA1, OPCML, RASSF1, SFPR1, and TWIST1 (p-value &lt;&lt; 0.0001). Using the current tissue collection and 5-fold cross validation, the four most significant loci (CDKN2A EX2, CDX2, HOXA1 and OPCML) individually distinguish lung adenocarcinoma from non-cancer lung with a sensitivity of 67–86% and specificity of 74–82%. DNA methylation of these loci did not differ significantly based on gender, race, age or tumor stage, indicating their wide applicability as potential lung adenocarcinoma markers. We applied random forests to determine a good classifier based on a subset of our loci and determined that combined use of the same four top markers allows identification of lung cancer tissue from non-lung cancer tissue with 94% sensitivity and 90% specificity. Conclusion The identification of eight CpG island loci showing highly significant hypermethylation in lung adenocarcinoma provides strong candidates for evaluation in patient remote media such as plasma and sputum. The four most highly ranked loci, CDKN2A EX2, CDX2, HOXA1 and OPCML, which show significant DNA methylation even in stage IA tumor samples, merit further investigation as some of the most promising lung adenocarcinoma markers identified to date.
Time- and Frequency-Domain Analyses of the Signal-Averaged ECG in Patients With Arrhythmogenic Right Ventricular Dysplasia
Authors: Osamu Kinoshita, Guy Fontaine, Fernando Rosas, Jorge Elias, Toru Iwa, Joelci Tonet, Gilles Lascault, Robert Frank
Journal: Circulation (1995)

Background Arrhythmogenic right ventricular dysplasia (ARVD) is characterized by recurrent ventricular tachycardia of right ventricular origin and a cardiomyopathy with hypokinetic areas involving the free wall of the right ventricle. Subjects have a risk of sudden cardiac death, particularly during sports and strenuous exercise. Routine clinical examinations may be normal, but fragmented or delayed electrograms are usually recorded in the right ventricle of these patients. However, the frequency with which late potentials are detected by conventional time-domain analysis of the signal-averaged ECG (SAECG) is not high. This study evaluated the usefulness of the frequency-domain analysis of the SAECG in addition to the conventional time-domain analysis for a screening test to detect patients with ARVD. Methods and Results SAECG was recorded by using a bipolar X, Y, and Z lead system in 28 patients with ARVD (mean age, 38±13 years) and 35 age-matched normal subjects (mean age, 35±11 years). The conventional time-domain analysis of the SAECG was performed at two different high-pass filter settings, 25 and 40 Hz, and the low-pass cutoff frequency was fixed at 250 Hz. The fast-Fourier transform analysis of SAECG was performed using a Blackman-Harris window. Area ratio 1 (area of 20 to 50 Hz)/(area of 0 to 20 Hz) and area ratio 2 (area of 40 to 100 Hz)/(area of 0 to 40 Hz) were calculated. In the conventional time-domain analysis, 20 (71%) and 18 (64%) patients had positive criteria at filter settings of 25 and 40 Hz, respectively. In the frequency-domain analysis, 18 (64%) and 20 (71%) patients had abnormal values in area ratios 1 and 2, respectively. Combining the time- and frequency-domain analyses, all patients were judged positive, with a sensitivity of 100% and a specificity of 94%. Conclusions Each result of the time- and frequency-domain analyses revealed that both methods had equivalent value. Combining the two domain analyses improved the sensitivity without reducing the specificity. These findings suggest that combining the time- and frequency-domain analyses of the SAECG may be useful as a screening test to detect patients with ARVD.
THE MYCOSES AS A THERAPEUTIC PROBLEM SURVEY OF 348 CASES.
Authors: F. MIEDZIŃASKI, J. LIPSKI
Journal: British Journal of Dermatology (1956)

Journal Article THE MYCOSES AS A THERAPEUTIC PROBLEM SURVEY OF 348 CASES. Get access F. MIEDZIŃASKI, M.D., F. MIEDZIŃASKI, M.D. Dermatological Clinic, Academy of Medicine, Gdańsk, Poland Search for other works by this author on: Oxford Academic Google Scholar J. LIPSKI, M.D. J. LIPSKI, M.D. Dermatological Clinic, Academy of Medicine, Gdańsk, Poland Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 68, Issue 6, 1 June 1956, Pages 200–203, https://doi.org/10.1111/j.1365-2133.1956.tb13206.x Published: 01 June 1956
Phylogeographic Analyses and Paleodistribution Modeling Indicate Pleistocene In Situ Survival of Hordeum Species (Poaceae) in Southern Patagonia without Genetic or Spatial Restriction
Authors: S. S. Jakob, E. Martinez-Meyer, F. R. Blattner
Journal: Molecular Biology and Evolution (2009)

Although many phylogeographic studies have been conducted to analyze the impact of the ice age on species history of Northern Hemisphere mountain plants, such studies are nearly absent for plants of the Southern Hemisphere, particularly for lowland vegetation units. These species should have been primarily influenced by climate cooling and changes in precipitation regime instead of glaciers covering their distribution areas. It is thought that New World lowland species generally evaded climate changes by equatorial migration during Pleistocene cold cycles and recolonized their habitats at higher latitudes when climate warmed up again. In contrast to Eurasia, latitudinal orientation of the major mountain ranges in the Americas made these migrations easily possible. In the huge steppe of the Patagonian plains and adjacent Andes of southern South America thrives a group of three sympatrically distributed diploid species of the barley genus Hordeum, which originated during the last 1.3 million years (My) from a common progenitor. To get insights into the speciation mode of the taxa and to test the hypothesis of longitudinal migration of steppe vegetation during the Pleistocene, we conducted population genetic and phylogeographic analyses based on sequences of the chloroplast trnL-F region from 922 individuals. We found a high number of chloroplast haplotypes shared among species, which indicate speciation through vicariance events. Analysis of the distribution of genetic diversity within and among species inferred an origin of Hordeum comosum in the Central Argentine Andes, whereas Hordeum patagonicum and Hordeum pubiflorum originated in southern Patagonia. The extant occurrence of H. comosum in southern Patagonia and H. pubiflorum northward along the Argentine Andes was caused by reciprocal migration after the origin of the species. Surprisingly, molecular data provided no evidence for range shifts toward the north during the last glacial maximum and recolonization of southerly habitats afterward, but indicated in situ survival of large populations of Hordeum species within their extant distribution ranges even in southernmost Patagonia and Tierra del Fuego. Ecoclimatic niche modeling used to reconstruct the potential paleodistribution areas of the species during the last glacial maximum shows that climate conditions were sufficient for the species to survive Pleistocene cold cycles in Patagonia without significant geographic restrictions. Molecular data together with ecological niche modeling indicate stable geographic distribution areas in two of the three species for at least the Holocene. As the Hordeum species are characteristic taxa of different steppe habitats, we speculate that the Patagonian steppe might be an old vegetation unit occurring for up to 4.5 My in southern South America.
Usefulness of Unipolar Electrograms to Detect Isthmus Block After Radiofrequency Ablation of Typical Atrial Flutter
Authors: Julian Villacastin, Jesus Almendral, Angel Arenal, Nicasio P. Castellano, Sergio Gonzalez, Mercedes Ortiz, Javier García, Bartolome Vallbona, Javier Moreno, Javier F. Portales, Esteban G. Torrecilla
Journal: Circulation (2000)

Background —RS morphology of the unipolar electrogram is associated with propagation of the wave front through the exploring electrode, whereas positive uniphasic (R) unipolar electrograms are characteristic of the end of activation. Methods and Results —Unipolar electrograms were recorded in 45 consecutive patients with atrial flutter who were undergoing radiofrequency ablation (RFA). Bidirectional cavotricuspid isthmus (CTI) block was achieved in 44 patients. The unipolar electrogram obtained before RFA at the low anterolateral right atrium during coronary sinus pacing changed from RS, rS, or QS to R or Rs in all patients after clockwise CTI block was obtained. The morphology of unipolar electrograms recorded close to the coronary sinus during pacing from the low anterolateral right atrium changed from RS or rS to R or Rs in all but 4 patients after counterclockwise CTI block. In the patient in whom CTI block was not achieved, the RS morphology of the unipolar electrogram remained unchanged. In 18 patients, the results of the RFA were assessed with only the unipolar electrogram. The unipolar electrogram correctly predicted 100% and 89% of the cases of clockwise and counterclockwise CTI block, respectively. Conclusions —The creation of CTI block is associated with an easily detectable loss of negative components and development of an R or Rs pattern of the unipolar electrogram recorded close to the ablation line while pacing at the opposite side of the CTI.