tbuckley/cabot-search huggingface dataset:
Randomised controlled trial of aminosidine (paromomycin) v sodium stibogluconate for treating visceral leishmaniasis in North Bihar, India Commentary: Some good news for treatment of visceral leishmaniasis in Bihar
Authors: T K Jha, P Olliaro, C P N Thakur, T P Kanyok, B L Singhania, I J Singh, N K P Singh, S Akhoury, S Jha, D. N J Lockwood
Journal: BMJ (1998)

<h3>Abstract</h3> <b>Objectives:</b> To assess the efficacy and tolerability of aminosidine compared with sodium stibogluconate for treating visceral leishmaniasis. <b>Design:</b> Randomised, unblinded, controlled trial with 180 day follow up. <b>Setting:</b> Kala-Azar Research Centre, Brahmpura, Muzaffarpur, Bihar, India. <b>Subjects:</b> People of either sex aged 6-50 years with symptoms and signs suggestive of visceral leishmaniasis (fever, loss of appetite, enlarged spleen) with leishmania amastigotes detected in Giemsa stained aspirates of spleen or bone marrow. <b>Interventions:</b> Aminosidine at three daily doses (12, 16, and 20 mg/kg) for 21 days and sodium stibogluconate 20 mg/kg/day for 30 days. <b>Main outcome measures:</b> Laboratory measures of efficacy: parasite count, haemoglobin concentration, white cell count, platelet count, serum albumin concentration. Clinical measures of efficacy: spleen size, fever, body weight, and liver size. Measures of safety: liver and renal function tests, reports of adverse events. <b>Results:</b> Of the 120 patients enrolled (30 per treatment arm), 119 completed treatment and follow up. Cure at end of follow up was achieved in 23 (77%), 28 (93%), and 29 (97%) patients treated with 12, 16, and 20 mg aminosidine/kg/day respectively, and in 19 (63%) patients given sodium stibogluconate. At 16 and 20 mg/kg/day, aminosidine was significantly more active than sodium stibogluconate in both clinical and laboratory measures of efficacy. No significant clinical or laboratory toxicity occurred in any treatment group. <b>Conclusions:</b> A 21 day course of aminosidine 16 or 20 mg/kg/day should be considered as first line treatment for visceral leishmaniasis in Bihar. <h3>Key messages</h3> Bihar in north east India accounts for about half the annual worldwide cases of visceral leishmaniasis, and resistance to standard treatment with sodium stibogluconate has been increasing We compared the safety and efficacy of three doses of aminosidine with standard regimen of sodium stibogluconate for treating visceral leishmaniasis in Bihar Aminosidine given at 16 or 20 mg/kg/day for 21 days was significantly more effective in producing final cure than sodium stibogluconate 20 mg/kg/day for 30 days Aminosidine had a low incidence of adverse reactions, including ototoxicity and renal toxicity, and was well tolerated Intramuscular injection of aminosidine 16 mg/kg/day for 21 days should be considered as a new first line treatment for visceral leishmaniasis in Bihar
Histidine Decarboxylase Deficiency Causes Tourette Syndrome: Parallel Findings in Humans and Mice
Authors: Lissandra Castellan Baldan, Kyle A. Williams, Jean-Dominique Gallezot, Vladimir Pogorelov, Maximiliano Rapanelli, Michael Crowley, George M. Anderson, Erin Loring, Roxanne Gorczyca, Eileen Billingslea, Suzanne Wasylink, Kaitlyn E. Panza, A. Gulhan Ercan-Sencicek, Kuakarun Krusong, Bennett L. Leventhal, Hiroshi Ohtsu, Michael H. Bloch, Zoë A. Hughes, John H. Krystal, Linda Mayes, Ivan de Araujo, Yu-Shin Ding, Matthew W. State, Christopher Pittenger
Journal: Neuron (2014)
Risk factors for healing of duodenal ulcer under antacid treatment: do ulcer patients need individual treatment?
Authors: S Massarrat, H G Muller, P Schmitz-Moormann
Journal: Gut (1988)

In order to identify the risk factors affecting the healing of duodenal ulcer, a clinical trial with effective dose of antacid was carried out in 53 patients. Duration of ulcer history, number of relapses, duration of the last and present relapse, number, duration and severity of pain attacks in the present ulcer relapse, pain radiation to back, vomiting, appetite, smoking habit, intake of analgesics and previous haemorrhage were registered. Number of ulcers, ulcer depth, bublar narrowing, erosions, duodenitis at initial endoscopy and healing of ulcer were assessed by one endoscopist. Basic and peak acid output were measured. The extent of duodenitis on the site opposite the ulcer was determined by histological examination. Sixty per cent of the duodenal ulcers were healed after three weeks. By univariate analysis, the following factors affect the healing; pain radiation to back and pain duration during treatment (p less than 0.001), multiple or deep ulcers, narrowing of duodenal bulb (p less than 0.01), number of pain attacks and poor appetite (p less than 0.05). By the stepwise logistic regression model, the following factors were selected as predictors for healing of duodenal ulcer with 76% correct classification: pain radiation to back (p = 0.002), deep ulcer (p = 0.013), multiple ulcers (p = 0.028). Number of cigarettes/day (p less than 0.007) and male sex (p = 0.036). By this model, the prediction of healing could be accurately assessed in 78% in a new sample. Individual treatment should be carried out on the basis of these factors.
TRAIL conjugated to nanoparticles exhibits increased anti-tumor activities in glioma cells and glioma stem cells in vitro and in vivo
Authors: Benny Perlstein, Susan A. Finniss, Cathie Miller, Hana Okhrimenko, Gila Kazimirsky, Simona Cazacu, Hae Kyung Lee, Nancy Lemke, Shlomit Brodie, Felix Umansky, Sandra A. Rempel, Mark Rosenblum, Tom Mikklesen, Shlomo Margel, Chaya Brodie
Journal: Neuro-Oncology (2012)

Glioblastomas (GBM) are characterized by resistance to chemotherapy and radiotherapy, and therefore, alternative therapeutic approaches are needed. TRAIL induces apoptosis in cancer but not in normal cells and is considered to be a promising anti-tumor agent. However, its short in vivo half-life and lack of efficient administration modes are serious impediments to its therapeutic efficacy. Nanoparticles (NP) have been used as effective delivery tools for various anticancer drugs. TRAIL was conjugated to magnetic ferric oxide NP by binding the TRAIL primary amino groups to activated double bonds on the surface of the NP. The effect of NP-TRAIL was examined on the apoptosis of glioma cells and self-renewal of glioma stem cells (GSCs). In addition, the ability of the NP-TRAIL to track U251 cell–derived glioma xenografts and to affect cell apoptosis, tumor volume, and survival among xenografted rats was also examined. Conjugation of TRAIL to NP increased its apoptotic activity against different human glioma cells and GSCs, as compared with free recombinant TRAIL. Combined treatment with NP-TRAIL and γ-radiation or bortezomib sensitized TRAIL-resistant GSCs to NP-TRAIL. Using rhodamine-labeled NP and U251 glioma cell–derived xenografts, we demonstrated that the NP-TRAIL were found in the tumor site and induced a significant increase in glioma cell apoptosis, a decrease in tumor volume, and increased animal survival. In summary, conjugation of TRAIL to NP increased its apoptotic activity both in vitro and in vivo. Therefore, NP-TRAIL represents a targeted anticancer agent with more efficient action for the treatment of GBM and the eradication of GSCs.
C-Reactive Protein, Insulin Resistance, Central Obesity, and Coronary Heart Disease Risk in Indian Asians From the United Kingdom Compared With European Whites
Authors: John C. Chambers, Shinichi Eda, Paul Bassett, Yusuf Karim, Simon G. Thompson, J.Ruth Gallimore, Mark B. Pepys, Jaspal S. Kooner
Journal: Circulation (2001)

Indian Asians in the United Kingdom have increased coronary heart disease (CHD) mortality compared with European whites, but the causes are not well understood. Increased circulating concentrations of C-reactive protein (CRP) are an independent risk factor for CHD. Therefore, we investigated this marker of inflammation in healthy UK Indian Asian and European white men. Methods and Results-- We measured serum CRP concentrations and conventional CHD risk factors in 1025 healthy male subjects (518 Indian Asians and 507 European whites) aged 35 to 60 years who were recruited at random from general practitioner lists. The geometric mean CRP concentration was 17% higher (95% confidence interval, 3% to 33%) in Indian Asians compared with European whites. CRP values were strongly associated with conventional CHD risk factors, measures of obesity, and metabolic disturbances associated with insulin resistance in both racial groups. The difference in CRP concentrations between Indian Asians and European whites remained after adjustment for conventional CHD risk factors but was eliminated by an adjustment for central obesity and insulin resistance score in Asians. On the basis of these results, we estimate that the processes underlying elevated CRP and/or increased CRP production itself are associated with an approximately 14% increase in population CHD risk among Indian Asians compared with European whites.CRP concentrations are higher in healthy Indian Asians than in European whites and are accounted for by greater central obesity and insulin resistance in Indian Asians. Our results suggest that inflammation or other mechanisms underlying elevated CRP values may contribute to the increased CHD risk among Indian Asians.
E-health empowers patients with ulcerative colitis: a randomised controlled trial of the web-guided ‘Constant-care’ approach
Authors: Margarita Elkjaer, Mary Shuhaibar, Johan Burisch, Yvonne Bailey, Hanne Scherfig, Birgit Laugesen, Søren Avnstrøm, Ebbe Langholz, Colm O'Morain, Elsebeth Lynge, Pia Munkholm
Journal: Gut (2010)

<h3>Background</h3> The natural history of ulcerative colitis requires continuous monitoring of medical treatment via frequent outpatient visits. The European health authorities9 focus on e-health is increasing. Lack of easy access to inflammatory bowel disease (IBD) clinics, patients9 education and understanding of the importance of early treatment at relapse is leading to poor compliance. To overcome these limitations a randomised control trial ‘Constant-care’ was undertaken in Denmark and Ireland. <h3>Methods</h3> 333 patients with mild/moderate ulcerative colitis and 5-aminosalicylate acid treatment were randomised to either a web-group receiving disease specific education and self-treatment via http://www.constant-care.dk or a control group continuing the usual care for 12 months. A historical control group was included to test the comparability with the control group. We investigated: feasibility of the approach, its influence on patients9 compliance, knowledge, quality of life (QoL), disease outcomes, safety and health care costs. <h3>Results</h3> 88% of the web patients preferred using the new approach. Adherence to 4 weeks of acute treatment was increased by 31% in Denmark and 44% in Ireland compared to the control groups. In Denmark IBD knowledge and QoL were significantly improved in web patients. Median relapse duration was 18 days (95% CI 10 to 21) in the web versus 77 days (95% CI 46 to 108) in the control group. The number of acute and routine visits to the outpatient clinic was lower in the web than in the control group, resulting in a saving of 189 euro/patient/year. No difference in the relapse frequency, hospitalisation, surgery or adverse events was observed. The historical control group was comparable with the control group. <h3>Conclusion</h3> The new web-guided approach on http://www.constant-care.dk is feasible, safe and cost effective. It empowers patients with ulcerative colitis without increasing their morbidity and depression. It has yet to be shown whether this strategy can change the natural disease course of ulcerative colitis in the long term.
Sphingosine kinase-1 and sphingosine 1-phosphate receptor 2 mediate Bcr-Abl1 stability and drug resistance by modulation of protein phosphatase 2A
Authors: Arelis Salas, Suriyan Ponnusamy, Can E. Senkal, Marisa Meyers-Needham, Shanmugam Panneer Selvam, Sahar A. Saddoughi, Elif Apohan, R. David Sentelle, Charles Smith, Christopher R. Gault, Lina M. Obeid, Hesham M. El-Shewy, Joshua Oaks, Ramasamy Santhanam, Guido Marcucci, Yusuf Baran, Sandeep Mahajan, Daniel Fernandes, Robert Stuart, Danilo Perrotti, Besim Ogretmen
Journal: Blood (2011)
Is the fast/slow allozyme variation at the Adh locus of Drosophila melanogaster an ancient balanced polymorphism? Citation]
Authors: D. J. Begun, A. J. Betancourt, C. H. Langley, W. Stephan
Journal: Molecular Biology and Evolution (1999)

Any general model of population genetics must be able to accommodate observations both of standing variation (polymorphism) and of evolutionary history (divergence). Interpretation of the connection (or lack thereof) between these two kinds of data impinges directly on our ideas of evolutionary mechanism. Studies of the alcohol dehydrogenase locus (Adh) in Drosophila melanogaster and its close relatives provide what is perhaps our most detailed description of variation and evolution of a gene at the molecular and phenotypic levels. There is abundant evidence that two common electrophoretic variants in D. melanogaster populations caused by a threonine (Fast)/lysine (Slow) polymorphism at codon 192 have different biochemical properties and are currently under some form of variable selection (reviewed in Powell 1997). Other polymorphisms at the locus may also be current targets of natural selection (Berry and Kreitman 1993), and epistatic effects among some of these polymorphisms must be considered (Stam and Laurie 1996). Molecular population genetic studies of Adh have revealed at least four interesting patterns. First, some fraction of the amino acid evolution in the melanogaster subgroup has been caused by natural selection (McDonald and Kreitman 1991). Second, a peak of excess silent polymorphisms is found at nucleotide sites that are closely linked to the Fast/ Slow polymorphism in D. melanogaster. The excess polymorphisms are incompatible with neutral molecular evolution; however, a model of balancing selection fits the data well (Kreitman and Hudson 1991). Third, the Fast electromorph in D. melanogaster appears to have increased in frequency in the recent past, as Fast haplotypes harbor little silent polymorphism and show little sequence divergence from Slow haplotypes (Kreitman 1983; Aquadro et al. 1986). Finally, correlated evolution of particular sites among different lineages suggests that epistatic selection acts on some property of Adh transcripts (Parsch, Tanda, and Stephan 1997). One message from these molecular analyses is that the evolutionary history of Adh is as complex as it is interesting. Despite the wealth of accumulated knowledge about Adh polymorphism and divergence, several questions remain. One of the mysteries associated with Adh nucleotide variation in D. melanogaster is the observation by Kreitman and Aguade (1986) and Kreitman and Hudson (1991)
Muscleblind-like 2-Mediated Alternative Splicing in the Developing Brain and Dysregulation in Myotonic Dystrophy
Authors: Konstantinos Charizanis, Kuang-Yung Lee, Ranjan Batra, Marianne Goodwin, Chaolin Zhang, Yuan Yuan, Lily Shiue, Melissa Cline, Marina M. Scotti, Guangbin Xia, Ashok Kumar, Tetsuo Ashizawa, H. Brent Clark, Takashi Kimura, Masanori P. Takahashi, Harutoshi Fujimura, Kenji Jinnai, Hiroo Yoshikawa, Mário Gomes-Pereira, Geneviève Gourdon, Noriaki Sakai, Seiji Nishino, Thomas C. Foster, Manuel Ares, Robert B. Darnell, Maurice S. Swanson
Journal: Neuron (2012)
ABVD plus radiotherapy versus EVE plus radiotherapy in unfavorable stage IA and IIA Hodgkin's lymphoma: results from an Intergruppo Italiano Linfomi randomized study
Authors: V. Pavone, U. Ricardi, S. Luminari, P. Gobbi, M. Federico, L. Baldini, E. Iannitto, G. Ucci, L. Marcheselli, L. Orsucci, E. Angelucci, M. Liberati, P. Gavarotti, A. Levis
Journal: Annals of Oncology (2008)
A qualitative study exploring the experiences of parents of children admitted to seven Dutch pediatric intensive care units
Authors: Jos M. Latour, Johannes B. van Goudoever, Beatrix Elink Schuurman, Marcel J. I. J. Albers, Nicolette A. M. van Dam, Eugenie Dullaart, Marc van Heerde, Carin W. M. Verlaat, Elise M. van Vught, Jan A. Hazelzet
Journal: Intensive Care Medicine (2010)

To explore parents' experiences during the admission of their children to a pediatric intensive care unit (PICU).Qualitative method using in-depth interviews. Thematic analysis was applied to capture parents' experiences. Thirty-nine mothers and 25 fathers of 41 children admitted to seven of the eight PICUs in university medical centers in The Netherlands were interviewed.Parents were interviewed within 1 month after their child's discharge from a PICU. Thematic analysis identified 1,514 quotations that were coded into 63 subthemes. The subthemes were categorized into six major themes: attitude of the professionals; coordination of care; emotional intensity; information management; environmental factors; parent participation. Most themes had an overarching relationship representing the array of experiences encountered by parents when their child was staying in a PICU. The theme of emotional intensity was in particular associated with all the other themes.The findings provided a range of themes and subthemes describing the complexity of the parental experiences of a PICU admission. The subthemes present a systematic and thematic basis for the development of a quantitative instrument to measure parental experiences and satisfaction with care. The findings of this study have important clinical implications related to the deeper understanding of parental experiences and improving family-centered care.
Systemic Soluble Receptor for Advanced Glycation Endproducts Is a Biomarker of Emphysema and Associated with AGER Genetic Variants in Patients with Chronic Obstructive Pulmonary Disease
Authors: Donavan T. Cheng, Deog Kyeom Kim, Debra A. Cockayne, Anton Belousov, Hans Bitter, Michael H. Cho, Annelyse Duvoix, Lisa D. Edwards, David A. Lomas, Bruce E. Miller, Niki Reynaert, Ruth Tal-Singer, Emiel F. M. Wouters, Alvar Agustí, Leonardo M. Fabbri, Alex Rames, Sudha Visvanathan, Stephen I. Rennard, Paul Jones, Harsukh Parmar, William MacNee, Gerhard Wolff, Edwin K. Silverman, Ruth J. Mayer, Sreekumar G. Pillai
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

Rationale: Emphysema in chronic obstructive pulmonary disease (COPD) can be characterized by high-resolution chest computed tomography (HRCT); however, the repeated use of HRCT is limited because of concerns regarding radiation exposure and cost.Objectives: To evaluate biomarkers associated with emphysema and COPD-related clinical characteristics, and to assess the relationships of soluble receptor for advanced glycation endproducts (sRAGE), a candidate systemic biomarker identified in this study, with single-nucleotide polymorphisms (SNPs) in the gene coding for RAGE (AGER locus) and with clinical characteristics.Methods: Circulating levels of 111 biomarkers were analyzed for association with clinical characteristics in 410 patients with COPD enrolled in the TESRA study. sRAGE was also measured in the ECLIPSE cohort in 1,847 patients with COPD, 298 smokers and 204 nonsmokers. The association between 21 SNPs in the AGER locus with sRAGE levels and clinical characteristics was also investigated.Measurements and Main Results: sRAGE was identified as a biomarker of diffusing capacity of carbon monoxide and lung density in the TESRA cohort. In the ECLIPSE cohort, lower sRAGE levels were associated with increased emphysema, increased Global Initiative for Chronic Obstructive Lung Disease stage, and COPD disease status. The associations with emphysema in both cohorts remained significant after covariate adjustment (P < 0.0001). One SNP in the AGER locus, rs2070600, was associated with circulating sRAGE levels both in TESRA (P = 0.0014) and ECLIPSE (7.07 × 10−16), which exceeded genome-wide significance threshold. Another SNP (rs2071288) was also associated with sRAGE levels (P = 0.01) and diffusing capacity of carbon monoxide (P = 0.01) in the TESRA study.Conclusions: Lower circulating sRAGE levels are associated with emphysema severity and genetic polymorphisms in the AGER locus are associated with systemic sRAGE levels.Clinical trial registered with www.clinicaltrials.gov (NCT 00413205 and NCT 00292552).
Early surgery versus initial conservative treatment in patients with spontaneous supratentorial lobar intracerebral haematomas (STICH II): a randomised trial
Authors: A David Mendelow, Barbara A Gregson, Elise N Rowan, Gordon D Murray, Anil Gholkar, Patrick M Mitchell
Journal: The Lancet (2013)

BackgroundThe balance of risk and benefit from early neurosurgical intervention for conscious patients with superficial lobar intracerebral haemorrhage of 10–100 mL and no intraventricular haemorrhage admitted within 48 h of ictus is unclear. We therefore tested the hypothesis that early surgery compared with initial conservative treatment could improve outcome in these patients.MethodsIn this international, parallel-group trial undertaken in 78 centres in 27 countries, we compared early surgical haematoma evacuation within 12 h of randomisation plus medical treatment with initial medical treatment alone (later evacuation was allowed if judged necessary). An automatic telephone and internet-based randomisation service was used to assign patients to surgery and initial conservative treatment in a 1:1 ratio. The trial was not masked. The primary outcome was a prognosis-based dichotomised (favourable or unfavourable) outcome of the 8 point Extended Glasgow Outcome Scale (GOSE) obtained by questionnaires posted to patients at 6 months. Analysis was by intention to treat. This trial is registered, number ISRCTN22153967.Findings307 of 601 patients were randomly assigned to early surgery and 294 to initial conservative treatment; 298 and 291 were followed up at 6 months, respectively; and 297 and 286 were included in the analysis, respectively. 174 (59%) of 297 patients in the early surgery group had an unfavourable outcome versus 178 (62%) of 286 patients in the initial conservative treatment group (absolute difference 3·7% [95% CI −4·3 to 11·6], odds ratio 0·86 [0·62 to 1·20]; p=0·367).InterpretationThe STICH II results confirm that early surgery does not increase the rate of death or disability at 6 months and might have a small but clinically relevant survival advantage for patients with spontaneous superficial intracerebral haemorrhage without intraventricular haemorrhage.FundingUK Medical Research Council.