tbuckley/cabot-search huggingface dataset:
Tackling treatment uncertainties together: the evolution of the James Lind Initiative, 2003–2013
Authors: Iain Chalmers, Patricia Atkinson, Mark Fenton, Lester Firkins, Sally Crowe, Katherine Cowan
Journal: Journal of the Royal Society of Medicine (2013)

Summary The James Lind Initiative (JLI) was established in 2003 in response to a call by the Medical Research Council, endorsed by the Department of Health (DH), for the creation of 'a communications and discussion forum on randomized controlled trials, involving patients, practitioners, research- ers, and others'. This brief was approached indirectly by encouraging more explicit acknowledgement of uncertainties about the effects of treatments. Between 2003 and 2013, the JLI developed the UK Database of Uncertainties about the Effects of Treatments (UK DUETs) to assemble and publish uncertainties (www.library.nhs.uk/duets/), and the James Lind Alliance (JLA) to provide a formal structure within which patients and clinicians could identify uncertainties and agree priorities for research (www.lindalliance.org). UK DUETs and the JLA have both now been mainstreamed, UK DUETs by incorporation within the National Institute for Health and Clinical Excellence (NICE), the JLA by designation as a partner organization of NIHR, managed by the NIHR Evaluation, Trials and Studies Coordinating Centre (NETSCC). Parallel to its development of methods for research prioritization, the Initiative has worked with others to produce printed and digital resources (www.jameslindlibrary.org; www.testingtreatments.org) to help enhance general knowledge about why it is important to address uncertainties about the effects of treat- ments; how to recognize rigorous tests of treatments; and how to reduce avoidable waste in research. The JLI will continue to work on these resources and themes over coming years.
Subjective Experience and Striatal Dopamine D2 Receptor Occupancy in Patients With Schizophrenia Stabilized by Olanzapine or Risperidone
Authors: L. de Haan
Journal: American Journal of Psychiatry (2000)

OBJECTIVE: The authors' goal was to study the relationship between subjective experience during treatment with olanzapine or risperidone and dopamine D2 receptor occupancy in stabilized patients with schizophrenia.METHOD: Subjective experience, psychopathology, and extrapyramidal symptoms were assessed, and D2 receptor occupancy was determined with [123I]iodobenzamide single photon emission computed tomography, in 22 patients whose schizophrenia was stabilized by olanzapine or risperidone.RESULTS: Subjective experience, depression, and negative symptoms were related to dopamine D2 receptor occupancy, but extrapyramidal symptoms were not.CONCLUSIONS: These results provide preliminary evidence that negative subjective experience is related to high D2 receptor occupancy. Longitudinal study is required because this relationship may have implications for dosing strategies.
Objective evaluation of small bowel and colonic transit time using pH telemetry in athletes with gastrointestinal symptoms
Authors: K A Rao, E Yazaki, D F Evans, R Carbon
Journal: British Journal of Sports Medicine (2004)

Background: Gastrointestinal (GI) disturbances are often reported by long distance runners and are more common in women, particularly after prolonged high intensity exercise. Objectives: To determine whether these symptoms could be associated with alterations in GI motility. Methods: Small bowel and colonic transit were measured using pH telemetry in a group of 11 female athletes (age 22 to 53 years), six of whom experienced lower GI symptoms during exercise. Subjects participated in two experimental sessions: a control measurement, where small bowel transit was estimated during a rest period (R) of six hours; and an exercise session (E), where small bowel transit was measured during a one hour period of high intensity exercise (cross country running) at &gt;70% V˙O 2 max. Colonic transit was estimated indirectly from determinations of whole gut transit time by radio-opaque marker. Results: Small bowel transit time was 3.5 to 10.6 h (R) and 3.0 to 8.7 h (E) in asymptomatic athletes, versus 4.0 to 6.6 h (R) and 4.6 to 7.3 h (E) in symptomatic athletes (NS). Colonic transit time was 35.0 to 62.5 h (R) and 30.5 to 70.9 h (E) in asymptomatic athletes versus 20.4 to 42.9 h (R) and 21.5 to 67.2 h (E) in symptomatic athletes (NS). Conclusions: Small bowel and colonic transit times were similar in the two groups in the rest and exercise sessions. The diarrhoea seen in this study did not result from accelerated colonic transit. Other mechanisms must be sought.
Genetic Polymorphisms of Human <b> <i>Flavin Monooxygenase 3</i> </b> in Sulindac-Mediated Primary Chemoprevention of Familial Adenomatous Polyposis
Authors: Irfan M. Hisamuddin, Mohammad A. Wehbi, Ann Chao, Hadley W. Wyre, Linda M. Hylind, Francis M. Giardiello, Vincent W. Yang
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Sulindac is a nonsteroidal anti-inflammatory drug (NSAID) effective in regressing adenomas in patients with familial adenomatous polyposis (FAP). However, a recent randomized trial showed that sulindac, when compared with placebo, failed to prevent the development of adenomatous polyps in genotypically positive but phenotypically negative FAP patients. The present study determined whether polymorphisms in the gene encoding flavin monooxygenase 3 (FMO3), a hepatic microsomal enzyme that inactivates sulindac, played a role in determining the efficacy of sulindac in preventing polyposis in this cohort of FAP patients. Experimental Design: Genotyping was performed on seven established FMO3 polymorphisms previously shown to have functional relevance—M66I, P153L, E158K, V257M, E305X, E308G, and R492W—in 21 and 20 FAP patients, who received sulindac and placebo, respectively. Results: None of the 41 patients exhibited heterozygous or homozygous M66I and R492W variant alleles, or homozygous P153L, V257M, and E305X variant alleles. Among sulindac-treated patients who did not develop adenomas (“responders”), 4 (33%) were homozygous for E158K and 2 (17%) were homozygous for E308G variant alleles. In contrast, none of the patients on sulindac who developed adenomas (“nonresponders”) exhibited homozygosity for either of the two variant alleles. In addition, polymorphisms in the E158K or E308G allele were associated with a significant reduction in mucosal prostanoid levels in patients treated with sulindac. Conclusions: Polymorphisms in FMO3, particularly at the E158K and E308G loci, may reduce activity in catabolizing sulindac and result in an increased efficacy to prevent polyposis in FAP.
Polyclonal Serum Free Light Chains: A Biomarker of Disease Prognosis or of Immune Senescence?
Authors: Michele Bibas
Journal: Journal of Clinical Oncology (2012)

growing body of literature on the prognostic role of elevated poly- clonal serum free light chains (sFLCs) in clinical settings. Of note, increased polyclonal sFLCs have been detected in conditions that are characterized by chronic B-cell activation: rheumatoid arthritis, Sjogren's syndrome, systemic lupus erythematosus, severe atopic and nonatopic asthma and dermatitis, idiopathic pulmonaryfibrosis, and chronic hypersensitivity pneumonitis. Furthermore, infections, dia- betesmellitus,renalimpairment,andinflammatoryboweldiseaseare significant known causes of polyclonal increase in sFLCs. 2,3 Because the incidence of these diseases increases with age, and aging is another cause of elevated polyclonal sFLCs, I would have expected that the authors 1 would include the presence of comorbidi- ties in their analysis. The sFLC half-life of only 2 to 6 hours would potentially indicate the immediate occurrence of B-cell dysfunction/ activity; thus, intrapatient variations are strictly correlated with the activity of the underlying disease and may be influenced by therapy. 3
Increased Expression of Human T Lymphocyte Virus Type I (HTLV-I) Tax11-19 Peptide–Human Histocompatibility Leukocyte Antigen A*201 Complexes on CD4+ CD25<b>+</b>T Cells Detected by Peptide-specific, Major Histocompatibility Complex–restricted Antibodies in Patients with HTLV-I–associated Neurologic Disease
Authors: Yoshihisa Yamano, Cyril J. Cohen, Norihiro Takenouchi, Karen Yao, Utano Tomaru, Hong-Chuan Li, Yoram Reiter, Steven Jacobson
Journal: The Journal of Experimental Medicine (2004)

Human T lymphocyte virus type I (HTLV-I)–associated chronic inflammatory neurological disease (HTLV-I–associated myelopathy/tropical spastic paraparesis [HAM/TSP]) is suggested to be an immunopathologically mediated disorder characterized by large numbers of HTLV-I Tax–specific CD8+ T cells. The frequency of these cells in the peripheral blood and cerebrospinal fluid is proportional to the amount of HTLV-I proviral load and the levels of HTLV-I tax mRNA expression. As the stimulus for these virus-specific T cells are immunodominant peptide–human histocompatibility leukocyte antigen (HLA) complexes expressed on antigen-presenting cells, it was of interest to determine which cells express these complexes and at what frequency. However, until now, it has not been possible to identify and/or quantify these peptide–HLA complexes. Using a recently developed antibody that specifically recognizes Tax11-19 peptide–HLA-A*201 complexes, the level of Tax11-19–HLA-A*201 expression on T cells was demonstrated to be increased in HAM/TSP and correlated with HTLV-I proviral DNA load, HTLV-I tax mRNA load, and HTLV-I Tax–specific CD8+ T cell frequencies. Furthermore, CD4+ CD25+ T cells were demonstrated to be the major reservoir of HTLV-I provirus as well as Tax11-19 peptide–HLA-A*201 complexes. These results indicate that the increased detection and visualization of peptide–HLA complexes in HAM/TSP CD4+ CD25+ T cell subsets that are shown to stimulate and expand HTLV-I Tax–specific CD8+ T cells may play an important role in the pathogenesis of HTLV-I–associated neurological disease.
Hematopoietic Stem Cells Expressing the Myeloid Lysozyme Gene Retain Long-Term, Multilineage Repopulation Potential
Authors: Min Ye, Hiromi Iwasaki, Catherine V Laiosa, Matthias Stadtfeld, Huafeng Xie, Susanne Heck, Bjorn Clausen, Koichi Akashi, Thomas Graf
Journal: Immunity (2003)
Distribution of B lymphocytes in nonsuppurative cholangitis in primary biliary cirrhosis
Authors: Yasuni Nakanuma
Journal: Hepatology (1993)

Primary biliary cirrhosis is characterized by the immune-mediated, nonsuppurative destruction of intrahepatic small bile ducts, with significant T-cell involvement. To date, B cells in livers of primary biliary cirrhosis patients have been ignored in immunopathological evaluations of nonsuppurative cholangitis. This study aimed to correlate the distribution of activated T and B cells with the histopathology of nonsuppurative cholangitis in primary biliary cirrhosis, with emphasis on B cell infiltration. The distribution of activated T and B cells and the histopathology in primary biliary cirrhosis were heterogeneous in bile ducts showing nonsuppurative cholangitis; they were also heterogeneous in various parts of a given bile duct. Although activated T cells were significantly involved in the occurrence of nonsuppurative cholangitis, B cell-predominant reaction or cholangitis and B-cell infiltration into the biliary epithelial layer were also prominent in some nonsuppurative cholangitis. Many bile ducts with nonsuppurative cholangitis of various histological types showed intermixed activated T- and B-cell infiltration. These findings indicate that immune mechanism(s) involving B cells and, probably, humoral immunity are at work in the occurrence of nonsuppurative cholangitis and the destruction of bile ducts in primary biliary cirrhosis. Cell-to-cell interactions of activated T and B cells should therefore be evaluated in livers of patients with primary biliary cirrhosis.
Insulin Resistance, Inflammation, and the Metabolic Syndrome Following Roux-en-Y Gastric Bypass Surgery in Severely Obese Subjects
Authors: Rosa Morínigo, Roser Casamitjana, Salvadora Delgado, Antonio Lacy, Ramon Deulofeu, Ignacio Conget, Silvia Barceló-Batllori, Ramon Gomis, Josep Vidal
Journal: Diabetes Care (2007)

Several studies have demonstrated the benefits of massive weight reduction following Roux-en-Y gastric bypass (RYGBP) on the metabolic syndrome (1–3). However, the time course of the effects of RYGBP on the metabolic syndrome components and its potential underlying mechanisms has not been reported. In recent years, it has been proposed that low-grade chronic inflammation is a critical factor underlying the metabolic syndrome (4–6). Alternatively, it has been proposed that the metabolic syndrome would be better explained by a combination of factors including but not limited to low-grade systemic inflammation (7). The aim of our study was to evaluate the time course of metabolic syndrome components, insulin sensitivity and inflammatory markers, following laparoscopic RYGBP in severely obese subjects. To discriminate the effects of modest (10% of initial body weight) versus massive weight loss on the evaluated parameters, we assessed subjects at 6 and 52 weeks after surgery.

A total of 36 Caucasian, severely obese subjects about to undergo RYGBP surgery (8) were evaluated (Table 1). Twenty normal-weight healthy volunteers, matched for sex and age with the obese subjects, served as controls (Table 1). The study was approved by the hospital ethics committee. Written informed consent was obtained from all participants. The 36 obese, operated subjects were evaluated within 8 weeks before RYGBP and again at 6 and 52 weeks after RYGBP. Control subjects were evaluated on a single occasion.

The diagnosis of the metabolic syndrome was based on the revised Adult Treatment Panel III criteria (9). Anthropometrical and blood pressure measurements were performed as previously described (10). Venous blood was collected after an overnight fast. Plasma glucose, total cholesterol, HDL cholesterol, triglyceride levels, insulin, adiponectin, and insulin sensitivity (homeostasis model assessment of insulin resistance [HOMA-IR]) were assessed …
Description of a novel grading system to assess the quality of bowel preparation in video capsule endoscopy
Authors: S. Van Weyenberg, H. De Leest, C. Mulder
Journal: Endoscopy (2011)

Background and study aims: Inadequate bowel preparation negatively influences the reliability of examinations by video capsule endoscopy (VCE). Currently, only subjective scales are available to describe mucosal visibility. We aimed to design a score that was derived directly from the VCE images.
Transglutaminases in Crohn's disease.
Authors: G D'Argenio, L Biancone, V Cosenza, N Della Valle, F P D'Armiento, M Boirivant, F Pallone, G Mazzacca
Journal: Gut (1995)

Transglutaminases are a family of Ca-dependent enzymes involved in various biological events. Circulating transglutaminase (factor XIIIa) is decreased in blood of patients with inflammatory bowel diseases. There is evidence that factor XIIIa and tissue type transglutaminase, present in cell cytosol, bind to various proteins of the extracellular matrix. This study examined the value of serum transglutaminase assay in the treatment and follow up of Crohn's disease and then investigated the intestinal location of both forms of transglutaminases by immunohistochemistry in normal and abnormal tissues. Serum transglutaminase activity was assayed in 36 patients with active Crohn's disease (CDAI > 150). Eighteen patients were studied prospectively from relapse into remission. A significant inverse correlation (p < 0.001) was found between circulating transglutaminase and Crohn's disease activity index; a correlation was also found between serum transglutaminase and serum orosomucoid (p < 0.01) and C reactive protein (p < 0.01). Patients were prospectively studied until clinical remission showed improvement in both their CDAI score mean (SD) (230 (46) to 72 (34), p < 0.01) and transglutaminase activity mean (SD) (0.61 (0.12) to 0.93 (0.13) mU/ml, p < 0.01). The immunohistochemistry assessment showed a colocalisation of factor XIIIa and tissue transglutaminase to the extracellular matrix of damaged tissues. In conclusion, these data confirm the value of serum transglutaminase assay as marker of Crohn's disease activity, extend the utility of serum transglutaminase assay to follow up of the disease, and emphasised the role of different types of transglutaminases in extracellular matrix assembly in the damaged tissues.
Protection From Retinopathy and Other Complications in Patients With Type 1 Diabetes of Extreme Duration
Authors: Jennifer K. Sun, Hillary A. Keenan, Jerry D. Cavallerano, Bela F. Asztalos, Ernst J. Schaefer, David R. Sell, Christopher M. Strauch, Vincent M. Monnier, Alessandro Doria, Lloyd Paul Aiello, George L. King
Journal: Diabetes Care (2011)

OBJECTIVE To assess complication prevalence and identify protective factors in patients with diabetes duration of ≥50 years. Characterization of a complication-free subgroup in this cohort would suggest that some individuals are protected from diabetes complications and allow identification of endogenous protective factors. RESEARCH DESIGN AND METHODS Cross-sectional, observational study of 351 U.S. residents who have survived with type 1 diabetes for ≥50 years (Medalists). Retinopathy, nephropathy, neuropathy, and cardiovascular disease were assessed in relation to HbA1c, lipids, and advanced glycation end products (AGEs). Retrospective chart review provided longitudinal ophthalmic data for a subgroup. RESULTS A high proportion of Medalists remain free from proliferative diabetic retinopathy (PDR) (42.6%), nephropathy (86.9%), neuropathy (39.4%), or cardiovascular disease (51.5%). Current and longitudinal (the past 15 years) glycemic control were unrelated to complications. Subjects with high plasma carboxyethyl-lysine and pentosidine were 7.2-fold more likely to have any complication. Of Medalists without PDR, 96% with no retinopathy progression over the first 17 years of follow-up did not experience retinopathy worsening thereafter. CONCLUSIONS The Medalist population is likely enriched for protective factors against complications. These factors might prove useful to the general population with diabetes if they can be used to induce protection against long-term complications. Specific AGE combinations were strongly associated with complications, indicating a link between AGE formation or processing with development of diabetic vasculopathy.
Neuromodulation: acetylcholine and memory consolidation
Authors: ME Hasselmo
Journal: Trends in Cognitive Sciences (1999)

Clinical and experimental evidence suggests that hippocampal damage causes more severe disruption of episodic memories if those memories were encoded in the recent rather than the more distant past. This decrease in sensitivity to damage over time might reflect the formation of multiple traces within the hippocampus itself, or the formation of additional associative links in entorhinal and association cortices. Physiological evidence also supports a two-stage model of the encoding process in which the initial encoding occurs during active waking and deeper consolidation occurs via the formation of additional memory traces during quiet waking or slow-wave sleep. In this article I will describe the changes in cholinergic tone within the hippocampus in different stages of the sleep-wake cycle and will propose that these changes modulate different stages of memory formation. In particular, I will suggest that the high levels of acetylcholine that are present during active waking might set the appropriate dynamics for encoding new information in the hippocampus, by partially suppressing excitatory feedback connections and so facilitating encoding without interference from previously stored information. By contrast, the lower levels of acetylcholine that are present during quiet waking and slow-wave sleep might release this suppression and thereby allow a stronger spread of activity within the hippocampus itself and from the hippocampus to the entorhinal cortex, thus facilitating the process of consolidation of separate memory traces.
Pharmacokinetics (PK) of Human Immunoglobulin 10% Administered Subcutaneously Alone or Following Recombinant Human Hyaluronidase (rHuPH20) in Primary Immunodeficiency Disease (PIDD) Patients
Authors: A. Rubinstein, R.L. Wasserman, I. Melamed, M. Stein, B. McCoy, W. Engl, H. Leibl, D. Gelmont, R.I. Schiff, W.J. Grossman
Journal: Journal of Allergy and Clinical Immunology (2011)
Sports injuries and illnesses during the London Summer Olympic Games 2012
Authors: Lars Engebretsen, Torbjørn Soligard, Kathrin Steffen, Juan Manuel Alonso, Mark Aubry, Richard Budgett, Jiri Dvorak, Manikavasagam Jegathesan, Willem H Meeuwisse, Margo Mountjoy, Debbie Palmer-Green, Ivor Vanhegan, Per A Renström
Journal: British Journal of Sports Medicine (2013)

The Olympic Movement Medical Code encourages all stakeholders to ensure that sport is practised without danger to the health of the athletes. Systematic surveillance of injuries and illnesses is the foundation for developing preventive measures in sport.To analyse the injuries and illnesses that occurred during the Games of the XXX Olympiad, held in London in 2012.We recorded the daily occurrence (or non-occurrence) of injuries and illnesses (1) through the reporting of all National Olympic Committee (NOC) medical teams and (2) in the polyclinic and medical venues by the London Organising Committee of the Olympic and Paralympic Games' (LOCOG) medical staff.In total, 10 568 athletes (4676 women and 5892 men) from 204 NOCs participated in the study. NOC and LOCOG medical staff reported 1361 injuries and 758 illnesses, equalling incidences of 128.8 injuries and 71.7 illnesses per 1000 athletes. Altogether, 11% and 7% of the athletes incurred at least one injury or illness, respectively. The risk of an athlete being injured was the highest in taekwondo, football, BMX, handball, mountain bike, athletics, weightlifting, hockey and badminton, and the lowest in archery, canoe slalom and sprint, track cycling, rowing, shooting and equestrian. 35% of the injuries were expected to prevent the athlete from participating during competition or training. Women suffered 60% more illnesses than men (86.0 vs 53.3 illnesses per 1000 athletes). The rate of illness was the highest in athletics, beach volleyball, football, sailing, synchronised swimming and taekwondo. A total of 310 illnesses (41%) affected the respiratory system and the most common cause of illness was infection (n=347, 46%).At least 11% of the athletes incurred an injury during the games and 7% of the athletes' an illness. The incidence of injuries and illnesses varied substantially among sports. Future initiatives should include the development of preventive measures tailored for each specific sport and the continued focus among sport bodies to institute and further develop scientific injury and illness surveillance systems.