tbuckley/cabot-search huggingface dataset:
Increased colonic bile acid exposure: a relevant factor for symptoms and treatment in IBS
Authors: Antal Bajor, Hans Törnblom, Mats Rudling, Kjell-Arne Ung, Magnus Simrén
Journal: Gut (2014)

Bile acids may play a role in the pathogenesis of IBS. We investigated the potential effects of bile acids entering the colon and its role in the symptom pattern in IBS.We measured 75Se-labelled homocholic acid-taurine (75SeHCAT) retention, and serum levels of 7α-hydroxy-4-cholesten-3-one (C4) and fibroblast growth factor (FGF) 19 in patients with IBS (n=141) and control subjects (75SeHCAT n=29; C4 and FGF19 n=435). In patients with IBS stool frequency and form, as well as GI symptom severity were registered, and in a proportion of patients colonic transit time and rectal sensitivity were measured (n=66). An 8-week open-label treatment with colestipol was offered to patients with 75SeHCAT <20%, and the effect of treatment was evaluated with IBS severity scoring system and adequate relief of IBS symptoms.Compared with controls, patients with IBS had lower 75SeHCAT values (p=0.005), higher C4c levels (C4 corrected for cholesterol) (p<0.001), but similar FGF19 levels. Abnormal 75SeHCAT retention (<10%) was seen in 18% of patients, whereas 23% had elevated C4c levels. Patients with IBS with 75SeHCAT retention <10% had more frequent stools, accelerated colonic transit time, rectal hyposensitivity, a higher body mass index, higher C4c and lower FGF19 levels. Colestipol treatment improved IBS symptoms (IBS severity scoring system 220±109 vs. 277±106; p<0.01), and 15/27 patients fulfilled criteria for treatment response (adequate relief ≥50% of weeks 5-8).Increased colonic bile acid exposure influences bowel habit and colonic transit time in patients with IBS. A high response rate to open label treatment with colestipol supports this, but placebo-controlled studies are warranted.
Incomplete Right Bundle-Branch Block
Authors: E. NEIL MOORE, JOHN P. BOINEAU, DONALD F. PATTERSON, James Alexander, A. J. Kennel
Journal: Circulation (1971)

Incomplete right bundle-branch block (IRBBB) usually is thought to be associated with abnormalities of the peripheral Purkinje system. This paper discusses the results of a study of six dogs from the same family and three nonrelated dogs with congenital IRBBB. Cardiac catheterization data were normal, and no evidence or history of cardiac disease was found before or after death. The depolarization sequence of ventricular epicardial activation was determined, and delays in right ventricular (RV) epicardial activation times were observed. Multipoint intramural electrodes were used to study intramural activation of the ventricular septum and free walls. The "electrical thickness" near the base of the RV mass was more than double that of the normal RV mass (9 vs 4 mm). Conduction along the right bundle branch (RBB) was analyzed during cardiopulmonary bypass, and electrograms recorded simultaneously from six sites along the RBB demonstrated that conduction velocity down the bundle was normal. The normal time of activation of the endocardial RV Purkinje fibers demonstrated that conduction in the right peripheral Purkinje system also was normal. Therefore, IRBBB in these dogs did not result from conduction abnormalities within the RV specialized conduction system. Interestingly, six of these dogs were members of the F 1 generation from a mating of a female beagle with pulmonary stenosis and a male beagle with ventricular septal defect. Both defects as well as IRBBB were observed in the F 2 generation. The present findings suggest that IRBBB may be a developmental variation in thickness of the RV free wall rather than an abnormality of the RV conduction system in cases without apparent heart disease. The developmental variant appears to have a genetic basis.
Year in review in Intensive Care Medicine 2011: I. Nephrology, epidemiology, nutrition and therapeutics, neurology, ethical and legal issues, experimentals
Authors: Massimo Antonelli, Marc Bonten, Jean Chastre, Giuseppe Citerio, Giorgio Conti, J. Randall Curtis, Daniel De Backer, Goran Hedenstierna, Michael Joannidis, Duncan Macrae, Jordi Mancebo, Salvatore M. Maggiore, Alexandre Mebazaa, Jean-Charles Preiser, Patricia Rocco, Jean-François Timsit, Jan Wernerman, Haibo Zhang
Journal: Intensive Care Medicine (2012)

Year in review in Intensive Care Medicine 2011 : I. Nephrology, epidemiology, nutrition and therapeutics, neurology, ethical and legal issues, experimentals
Somatostatin therapy of acute experimental pancreatitis.
Authors: P G Lankisch, H Koop, K Winckler, U R Folsch, W Creutzfeldt
Journal: Gut (1977)

Because somatostatin (SRIF) reduces exocrine pancreatic secretion, its effect on acute pancreatitis was investigated in rats. Linear SRIF reduced serum amylase and lipase but had no effect on pancreatic necrosis, oedema, leucocyte infiltration, and enzyme content. The mortality rate was not reduced. These results do not recommend the use of SRIF in the treatment of acute pancreatitis.
Is IL-10 a Good Target to Inhibit Choroidal Neovascularisation in Age-Related Macular Disease?
Authors: Sue Lightman, Virginia Calder
Journal: PLoS Medicine (2006)

Age-related macular disease (AMD) occurs most frequently in people aged 60 years and older and affects the central part of the retina, causing distortion or loss of central vision. The disease is the leading cause of blindness in people aged 60 years and older in the developed world and causes milder visual loss in a much greater number (about 25 percent of people aged 60 years and older in the developed world have some degree of visual loss because of AMD). AMD generally involves both eyes, although they may not be affected at the same time or to the same degree.

There are two forms of AMD: dry and wet. About 90 percent of patients with AMD have the dry atrophic type, for which there is currently no treatment, while 10 percent have wet AMD. Wet AMD causes the most severe visual loss and is the most aggressive form of the disease. In the wet form, choroidal blood vessels grow into the retina (choroidal neovascularisation [CNV]) but do not have the characteristic tight barriers of normal retinal blood vessels and so leak fluid into the retina. Such leakage often occurs under the central part of the retina—the macula—which is needed for visual detail. Scar tissue follows and leads to permanent severe visual loss.

In recent years, new forms of treatment for wet AMD have come into clinical practice following clinical trials. These new treatments are: (1) vitamins (the Age Related Eye Disease Study found that taking high levels of antioxidants and zinc can reduce the risk of developing advanced AMD by about 25 percent [1]); photodynamic therapy; and the most recently developed treatment, anti–vascular endothelial growth factor (anti-VEGF), which, when injected into the vitreous, has been helpful in preventing further visual loss and new vessel regression [2].
Visual prediction as indicated by perceptual adaptation to temporal delays and discrete stimulation
Authors: Douglas W. Cunningham
Journal: Behavioral and Brain Sciences (2008)

Abstract Analogous to prism adaptation, sensorimotor compensation for existing neural delays has been clearly demonstrated. This system can also adapt to new delays, both internal and external. This seems to occur at least partially in the sensor systems, and works for discrete, stationary events. This provides additional evidence for visual prediction, but not in a manner that is consistent with spatial extrapolation.
Loss of genes implicated in gastric function during platypus evolution
Authors: Gonzalo R Ordoñez, LaDeana W Hillier, Wesley C Warren, Frank Grützner, Carlos López-Otín, Xose S Puente
Journal: Genome biology (2008)

The duck-billed platypus (Ornithorhynchus anatinus) belongs to the mammalian subclass Prototheria, which diverged from the Theria line early in mammalian evolution. The platypus genome sequence provides a unique opportunity to illuminate some aspects of the biology and evolution of these animals.We show that several genes implicated in food digestion in the stomach have been deleted or inactivated in platypus. Comparison with other vertebrate genomes revealed that the main genes implicated in the formation and activity of gastric juice have been lost in platypus. These include the aspartyl proteases pepsinogen A and pepsinogens B/C, the hydrochloric acid secretion stimulatory hormone gastrin, and the alpha subunit of the gastric H+/K+-ATPase. Other genes implicated in gastric functions, such as the beta subunit of the H+/K+-ATPase and the aspartyl protease cathepsin E, have been inactivated because of the acquisition of loss-of-function mutations. All of these genes are highly conserved in vertebrates, reflecting a unique pattern of evolution in the platypus genome not previously seen in other mammalian genomes.The observed loss of genes involved in gastric functions might be responsible for the anatomical and physiological differences in gastrointestinal tract between monotremes and other vertebrates, including small size, lack of glands, and high pH of the monotreme stomach. This study contributes to a better understanding of the mechanisms that underlie the evolution of the platypus genome, might extend the less-is-more evolutionary model to monotremes, and provides novel insights into the importance of gene loss events during mammalian evolution.
Non-steroidal anti-inflammatory drugs and risk of lower gastrointestinal adverse events: a nationwide study in Taiwan
Authors: C.-H. Chang, J.-W. Lin, H.-C. Chen, C.-W. Kuo, W.-Y. Shau, M.-S. Lai
Journal: Gut (2011)

<h3>Objective</h3> Only limited studies have evaluated the risk of non-selective non-steroidal anti-inflammatory drugs (nsNSAIDs) and coxibs for lower gastrointestinal (GI) adverse outcomes. The objective of this study was to evaluate risks of lower GI adverse events associated with use of celecoxib, oral and parenteral nsNSAIDs. <h3>Design</h3> Retrospective case–crossover study. <h3>Setting</h3> Records of all patients aged ≥20 years hospitalised for lower GI adverse events (bleeding from small or large intestine, perforation, and complicated diverticular disease) in 2006 were retrieved using ICD-9-CM diagnosis codes from inpatient claims from the Taiwan National Health Insurance database. <h3>Interventions</h3> Case periods were defined for each patient as 1–30 days prior to hospital admission date and control period as 91–120 days prior to hospital admission date. The pharmacy prescription database was searched for NSAID use during case and control periods. <h3>Main outcome measures</h3> We calculated adjusted self-matched ORs and 95% CIs with a conditional logistic regression model to determine the associations between NSAID use and lower GI adverse outcomes. <h3>Results</h3> A total of 1297 patients hospitalised for lower GI adverse events were included. Celecoxib was associated with an adjusted OR of 2.33 (95% CI 0.97 to 5.59); the association became statistically significant (OR: 3.26, 95% CI 1.07 to 9.91) when a different control period (31–60 days) was applied. Both oral and parenteral nsNSAIDs significantly increased risk for lower GI adverse events (OR: 2.26, 95% CI 1.78 to 2.85 and OR: 5.64, 95% CI 3.24 to 9.82, respectively). <h3>Conclusions</h3> Oral and parenteral NSAIDs were associated with significantly increased risk for lower GI adverse events. Celecoxib also increased risk to a comparable extent, despite risk estimates being affected slightly by the control period chosen for comparison. The association of NSAIDs with specific lower GI adverse events and long-term complications requires further investigation.
One Fish, Two Fish, Blowfish, Blue Fish
Authors: D. O'Neill
Journal: BMJ (2011)

As a medical student I was well and truly “Kubler-Rossed,” becoming a follower of the theory of five stages of grief outlined in the 1969 book On Death and Dying . It was only some time later that I realised we were at the receiving end of an evangelical zeitgeist wherein conviction seemed to over-rule calmer reflection. Instead of being viewed as an important practical and reflective addition to our ways of considering reactions to serious illness and death, disciples of Elisabeth Kubler-Ross, in their enthusiasm, often allowed the concept to assume the characteristics of dogma. Indeed in 1985 Kubler-Ross expressed regret for having referred to them as stages, …
Pilot Induction Regimen Incorporating Pharmacokinetically Guided Topotecan for Treatment of Newly Diagnosed High-Risk Neuroblastoma: A Children's Oncology Group Study
Authors: Julie R. Park, Jeffrey R. Scott, Clinton F. Stewart, Wendy B. London, Arlene Naranjo, Victor M. Santana, Peter J. Shaw, Susan L. Cohn, Katherine K. Matthay
Journal: Journal of Clinical Oncology (2011)

To assess the feasibility of adding dose-intensive topotecan and cyclophosphamide to induction therapy for newly diagnosed high-risk neuroblastoma (HRNB).Enrolled patients received two cycles of topotecan (approximately 1.2 mg/m(2)/d) and cyclophosphamide (400 mg/m(2)/d) for 5 days followed by four cycles of multiagent chemotherapy (Memorial Sloan-Kettering Cancer Center [MSKCC] regimen). Pharmacokinetically guided topotecan dosing (target systemic exposure with area under the curve of 50 to 70 ng/mL/hr) was performed. Peripheral-blood stem cell (PBSC) harvest and surgical resection of residual primary tumor occurred after cycles 2 and 5, respectively. Patients achieving at least a partial response received myeloablative chemotherapy with PBSC rescue and radiation to the presurgical primary tumor volume. Oral 13-cis-retinoic acid maintenance therapy was administered twice daily for 14 days in six 28-day cycles.Thirty-one patients were enrolled onto the study. No deaths related to toxicity or dose-limiting toxicities occurred during induction. Mucositis rarely occurred after topotecan cycles (9.7%) in contrast to 30% after MSKCC cycles. Thirty patients underwent PBSC collection with median 31.1 × 10(6) CD34+ cells/kg (range, 1.8 to 541.8 × 10(6) CD34+ cells/kg), all negative for tumor contamination by immunocytochemical analysis. Targeted topotecan systemic exposure was achieved in 26 (84%) of 31 patients. At the end of induction, 26 patients (84%) had tumor response and one patient had progressive disease. In the overall cohort, 3-year event-free and overall survival were 37.8% ± 9.4% and 57.1% ± 9.4%, respectively.This pilot induction regimen was well tolerated with expected and reversible toxicities. These data support investigation of efficacy in a phase III clinical trial for newly diagnosed HRNB.
Re-expression of skeletal actin and regulation of 1 adrenoceptor signalling in DOCA-salt hypertension in rats
Authors: L. G Meggs, H.-e. Huang, J. Tillotson, J. M Capasso, P. Anversa
Journal: Cardiovascular Research (1992)

Journal Article Re-expression of α skeletal actin and regulation of α1 adrenoceptor signalling in DOCA-salt hypertension in rats Get access Leonard G Meggs, Leonard G Meggs Department of Medicine, New York Medical College, Valhalla, New York 10595, USA: L G Meggs, H Huang, J Tillotson, J M Capasso, P Anversa. Correspondence to Dr Anversa; reprint requests to Dr Meggs. Search for other works by this author on: Oxford Academic PubMed Google Scholar Har-er Huang, Har-er Huang Department of Medicine, New York Medical College, Valhalla, New York 10595, USA: L G Meggs, H Huang, J Tillotson, J M Capasso, P Anversa. Search for other works by this author on: Oxford Academic PubMed Google Scholar Joanne Tillotson, Joanne Tillotson Department of Medicine, New York Medical College, Valhalla, New York 10595, USA: L G Meggs, H Huang, J Tillotson, J M Capasso, P Anversa. Search for other works by this author on: Oxford Academic PubMed Google Scholar Joseph M Capasso, Joseph M Capasso Department of Medicine, New York Medical College, Valhalla, New York 10595, USA: L G Meggs, H Huang, J Tillotson, J M Capasso, P Anversa. Search for other works by this author on: Oxford Academic PubMed Google Scholar Piero Anversa Piero Anversa Department of Medicine, New York Medical College, Valhalla, New York 10595, USA: L G Meggs, H Huang, J Tillotson, J M Capasso, P Anversa. Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 26, Issue 9, September 1992, Pages 878–885, https://doi.org/10.1093/cvr/26.9.878 Published: 01 September 1992 Article history Received: 10 December 1991 Accepted: 18 March 1992 Published: 01 September 1992
Cutaneous toxicities associated with vemurafenib therapy in 107 patients with<i>BRAF</i>V600E mutation-positive metastatic melanoma, including recognition and management of rare presentations
Authors: R. Sinha, J. Larkin, M. Gore, L. Fearfield
Journal: British Journal of Dermatology (2015)

Vemurafenib significantly improved overall survival compared with dacarbazine in patients with metastatic or unresectable BRAF V600E-positive melanoma in the BRIM-3 trial. However, vemurafenib was associated with a number of skin-related adverse events (AEs).To investigate the incidence and management of vemurafenib-associated skin AEs.This retrospective, observational study included adult patients with stage IIIC or IV melanoma who received vemurafenib between March 2010 and August 2013. Patients received oral vemurafenib 960 mg twice daily, with dose interruptions and reductions allowed for AE management.In total 107 patients were treated with vemurafenib during the study period. The most frequent clinically important skin-related AEs were rash (64%), squamoproliferative growths (41%), photosensitivity (40%) and squamous cell carcinoma (SCC) or keratoacanthoma (KA; 20%). Rare cases of granulomatous dermatitis and cutaneous T-cell lymphoma were also found. Rash was manageable with corticosteroids and dose modifications; squamoproliferative growths and SCCs/KAs were treated with cryotherapy and surgical excision, respectively. Patients were counselled regarding phototoxicity. The uncontrolled nature and retrospective design of the study, and the small patient numbers are limitations.Vemurafenib appears to have a predictable and manageable AE profile. Proactive management can limit the impact of AEs on patients, allowing treatment to continue despite toxicities.
Hepatitis B virus X (HBx) induces tumorigenicity of hepatic progenitor cells in 3,5-diethoxycarbonyl-1,4-dihydrocollidine-treated HBx transgenic mice
Authors: Chao Wang, Wen Yang, He–Xin Yan, Tao Luo, Jian Zhang, Liang Tang, Fu–Quan Wu, Hui–Lu Zhang, Le–Xing Yu, Long–Yi Zheng, Yu–Qiong Li, Wei Dong, Ya–Qin He, Qiong Liu, Shan–Shan Zou, Yan Lin, Liang Hu, Zhong Li, Meng–Chao Wu, Hong–Yang Wang
Journal: Hepatology (2011)

Hepatitis B virus X (HBx) protein is implicated in hepatitis B virus (HBV)–associated liver carcinogenesis. However, it remains unclear whether HBx–expressing hepatic progenitor cells (HPCs) are attributed to liver tumor formation. In this study, by using HBx transgenic mice and a 3,5–diethoxycarbonyl–1,4–dihydrocollidine (DDC)–induced liver injury model, the relationship between HBx expression and tumorigenicity of HPCs was analyzed. Compared with control mice, an elevated number of EpCAM+ cells with characteristics of HPCs was observed in HBx mice after 1 month and 4 months of DDC diet feeding. All HBx transgenic mice developed liver tumors characterized by histological features of both hepatocellular carcinoma (HCC) and cholangiocarcinoma after 7 months of DDC feeding. Notably, EpCAM+ HPCs isolated from premalignant HBx mice exposed to a DDC diet for 4 months formed subcutaneous mixed–lineage tumors (four out of six) in nonobese diabetic/severe–combined immunodeficient (NOD/SCID) mice, and none of the cells from wildtype (WT) induced tumor, indicating that HBx may induce malignant transformation of HPCs that contributes to tumorigenesis. We also found higher titers of circulating interleukin (IL)–6, activities of IL–6/STAT3, and Wnt/β–catenin signaling pathways in HBx transgenic mice, suggesting HBx may induce intrinsic changes in HPCs by way of the above signaling that enables HPCs with tumorigenicity potential. Finally, clinical evidence showed that high HBx expression in human HBV–related HCC was statistically associated with expansion of EpCAM+ or OV6+ tumor cells and aggressive clinicopathologic features. Conclusion : HBx induces intrinsic cellular transformation promoting the expansion and tumorigenicity of HPCs in DDC–treated mice, which may be a possible origin for liver cancer induced by chronic hepatitis infection. (Hepatology 2012)
Fitness Costs of Doc Expression Are Insufficient to Stabilize Its Copy Number in Drosophila melanogaster
Authors: H.-P. Yang
Journal: Molecular Biology and Evolution (2003)

The stable coexistence of transposable elements (TEs) with their host genome over long periods of time suggests TEs have to impose some deleterious effect upon their host fitness. Three mechanisms have been proposed to account for the deleterious effect caused by TEs: host gene interruptions by TE insertions, chromosomal rearrangements by TE-induced ectopic recombination, and costly TE expression. However, the relative importance of these mechanisms remains controversial. Here, we test specifically if TE expression accounts for the host fitness cost imposed by TE insertions. In the retrotransposon Doc, expression requires binding of the host RNA polymerase to the internal promoter. If expression of Doc elements is deleterious to their host, Doc copies with promoters would be more strongly selected against and would persist in the population for shorter periods of time compared with Docs lacking promoters. We tested this prediction using sequence-specific amplified polymorphism (SSAP) analyses. We compared the populations of these two types of Doc elements in two sets of lines of Drosophila melanogaster: selection-free isogenic lines accumulating new Doc insertions and isogenized isofemale lines sampled from a natural population. We found that (1) there is no difference in the proportion of promoter-bearing and promoter-lacking copies between sets of lines, and (2) the site occupancy distribution of promoter-bearing copies does not skew toward lower frequency compared with that of promoter-lacking copies. Thus, selection against promoter-bearing copies does not appear to be stronger than that of promoter-lacking copies. Our results show that expression is not playing a major role in stabilizing Doc copy numbers.