tbuckley/cabot-search huggingface dataset:
Carbenoxolone sodium in the treatment of gastric ulcer with special reference to side-effects.
Authors: A G Turpie, T J Thomson
Journal: Gut (1965)

EDITORIAL SYNOPSIS This paper indicates the need for close clinical and biochemical observation of the patient during treatment with carbenoxolone.In 1962, Doll, Hill, Hutton, and Underwood reported the results of a clinical trial of a triterpenoid liquorice compound, carbenoxolone sodium (Biogastrone), in the treatment of gastric and duodenal ulcer.They suggested that carbenoxolone sodium promotes the healing of gastric ulcers.The results in patients with duodenal ulcer were not significantly different from those receiving placebo tablets.Of 58 patients who were given the active drug in a dose of 100 mg.three times daily for four weeks, 10 (17 %) developed oedema.In 1965, Doll, Hill, and Hutton, in a further series, re-affirmed the value of carbenoxolone sodium in promoting the reduction in size of gastric ulcers.Twenty-four patients were treated as out-patients using doses of 75 to 100 mg.three times daily of carbenoxolone sodium.In this series, a liability to fluid retention was again noted: 21 %
Cognitive Effects of Antipsychotic Drugs in First-Episode Schizophrenia and Schizophreniform Disorder: A Randomized, Open-Label Clinical Trial (EUFEST)
Authors: Michael Davidson, Silvana Galderisi, Mark Weiser, Nomi Werbeloff, Wolfgang W Fleischhacker, Richard S Keefe, Han Boter, Ireneus P M Keet, Dan Prelipceanu, Janusz K Rybakowski, Jan Libiger, Martina Hummer, Sonia Dollfus, Juan J López-Ibor, Luchezar G Hranov, Wolfgang Gaebel, Joseph Peuskens, Nils Lindefors, Anita Riecher-Rössler, René S Kahn
Journal: American Journal of Psychiatry (2009)

Objective: Cognitive impairment, manifested as mild to moderate deviations from psychometric norms, is present in many but not all schizophrenia patients. The purpose of the present study was to compare the effect of haloperidol with that of second-generation antipsychotic drugs on the cognitive performance of patients with schizophreniform disorder or first-episode schizophrenia. Methods: Subjects were 498 patients with schizophreniform disorder or first-episode schizophrenia who were randomly assigned to open-label haloperidol (1 to 4 mg/day [N=103]), amisulpride (200 to 800 mg/day [N=104]), olanzapine (5 to 20 mg/day [N=105]), quetiapine (200 to 750 mg/day [N=104]), or ziprasidone (40 to 160 mg/day [N=82]). The Rey Auditory Verbal Learning Test, Trail Making Test Part A and Part B, WAIS Digit Symbol Test, and Purdue Pegboard Test were administered at baseline and the 6-month follow-up evaluation. Results: Compared with scores at baseline, composite cognitive test scores improved for all five treatment groups at the 6-month follow-up evaluation. However, there were no overall differences among the treatment groups. In addition, there was a weak correlation between the degree of cognitive improvement and changes in Positive and Negative Syndrome Scale scores. Conclusion: Treatment with antipsychotic medication is associated with moderate improvement in the cognitive test performance of patients who have schizophreniform disorder or who are in their first episode of schizophrenia. The magnitude of improvement does not differ between treatment with haloperidol and treatment with second-generation antipsychotics. Moreover, cognitive improvement is weakly related to symptom change.
Hormone Replacement Therapy and Adenoma Recurrence: Implications for Its Role in Colorectal Cancer Risk
Authors: M. E. Martinez
Journal: JNCI Journal of the National Cancer Institute (2001)

In this issue of the Journal, Woodson et al. (1) present findings on the role of hormone replacement therapy (HRT) and the risk of adenoma recurrence from a prospective study nested in the Polyp Prevention Trial (PPT). Their results show that current HRT use is not associated with recurrence of adenomatous polyps. However, the investigators did observe a statistically significant interaction by age. Among women aged 62 years and older, an inverse association between HRT use and the risk of adenoma recurrence was shown (odds ratio [OR] 0.58; 95% confidence interval [CI] 0.35 to 0.97), whereas among women aged less than 62 years, an increased risk was observed (OR 1.99; 95% CI 1.11 to 3.55). There was also a suggestion of a negative association between HRT use and the risk of distal adenomas and a positive association between HRT use and the risk of proximal adenomas. The results of the study by Woodson et al. (1) do not support the majority of the published literature regarding HRT use and colorectal cancer. For example, when compared with never use, ever use of HRT is associated with a 20% reduction in the risk of colon cancer, and current use is associated with a 30% reduction in risk (2). The few existing case–control studies (3–5) regarding adenoma prevalence also support an inverse association between HRT use and the risk of colorectal adenoma. The results of the study by Woodson et al. (1) are, however, supported by those of the Nurses’ Health Study (6), a prospective study of 21 153 women who underwent a colonoscopy or sigmoidoscopy for screening purposes and in whom 838 women had distal adenomatous polyps during 14 years of follow-up. In the Nurses’ Health Study (6), no association was observed between current HRT use and the relative risk (RR) of adenomas (RR 0.91; 95% CI 0.77 to 1.08). However, there was a statistically significant inverse association between HRT use and the risk of adenomas 1 cm or larger in size (RR 0.74; 95% CI 0.55 to 0.99). It was not possible to test the same hypothesis in the PPT (1) because of the small number of large recurrent adenomas. Because the study by Woodson et al. (1) was nested within a trial of adenoma recurrence, a common study design for colorectal cancer chemoprevention, the study population comprises individuals with a history of adenomatous polyps. After a cleanout colonoscopy for the removal of potentially missed polyps, participants were followed for 3 years, at which time they underwent an end-point colonoscopy for the detection of additional adenomas. In the present study, enrollment was restricted to women in whom an adenomatous polyp had already formed. However, at baseline or enrollment, approximately 40% of the women had developed an adenoma while receiving HRT. Thus, an argument can be made that these are women who had already undergone the initiation-phase of carcinogenesis and, furthermore, that HRT was not highly protective against the formation of a baseline adenoma.
THE RELEASE OF SPECIFIC BACTERICIDAL ANTIBODIES BY ENDOTOXIN
Authors: J. Gabriel Michael
Journal: The Journal of Experimental Medicine (1966)

Studies presented in this report are concerned with the effect of endotoxin upon the release of bactericidal antibodies as determined by the agar plaque technique. We found that shortly after the injection of mice with small amounts of endotoxin the number of plaque-forming cells in the spleen was substantially reduced and remained low for about 12 hr. At the same time the titer of specific bactericidal antibodies in the circulation was increased, 6-mercaptopurine was shown to be an effective suppressor of the immune response by inhibiting the multiplication of bactericidin-forming cells. However, administration of this drug did not modify the initial responses of antibodies and plaque-forming cells to endotoxin. Thus, we postulate that endotoxin does not induce destruction and subsequent reconstitution of bactericidin-forming cells, but that the observed changes represent a release of preformed antibodies from competent cells. For a limited time, thereafter, these cells become inactive, but soon resume their normal function of releasing bactericidal antibodies.
Chronic Ethanol Increases Adeno-Associated Viral Transgene Expression in Rat Liver via Oxidant and NFκB-Dependent Mechanisms
Authors: Michael D. Wheeler, Hiroshi Kono, Ivan Rusyn, Gavin E. Arteel, Douglas McCarty, Richard Jude Samulski, Ronald G. Thurman
Journal: Hepatology (2000)

Recombinant adeno–associated virus (rAAV) transduction is limited in vivo , yet can be enhanced by hydroxyurea, ultraviolet–irradiation, or adenovirus coinfection, possibly via mechanisms involving stress in the host cell. Because chronic ethanol induces oxidative stress, it was hypothesized that chronic ethanol would increase rAAV transduction in vivo . To test this hypothesis, rAAV encoding β–galactosidase was given to Wistar rats that later received either ethanol diet or high–fat control diet via an enteral–feeding protocol for 3 weeks. Expression and activity of β–galactosidase in the liver were increased nearly 5–fold by ethanol. The increase in transgene expression was inhibited by antioxidant diphenylene iodonium (DPI), which is consistent with the hypothesis that ethanol causes an increase in rAAV transduction via oxidative stress. Ethanol increased DNA synthesis only slightly; however, it increased the nuclear transcription factor κB (NFκB) 4–fold, a phenomenon also sensitive to DPI. Moreover, a 6–fold increase in rAAV transgene expression was observed in an acute ischemia–reperfusion model of oxidative stress. Transgene expression was transiently increased 24 hours after ischemia–reperfusion 3 days and 3 weeks after rAAV infection. Further, adenoviral expression of superoxide dismutase or IκBα superrepressor inhibited rAAV transgene expression caused by ischemia–reperfusion. Therefore, it is concluded that ethanol increases rAAV transgene expression via mechanisms dependent on oxidative stress, and NFκB likely through enhancement of cytomegaloviral (CMV) promoter elements. Alcoholic liver disease is an attractive target for gene therapy because consumption of ethanol could theoretically increase expression of therapeutic genes ( e.g. , superoxide dismutase). Moreover, this study has important implications for rAAV gene therapy and potential enhancement and regulation of transgene expression in liver.
Effects of Genomic Polymorphisms on the Course of Sepsis
Authors: FRANK STU[Combining Diaeresis]BER
Journal: Journal of the American Society of Nephrology (2001)

Sepsis and its sequelae are still a major cause of morbidity and mortality on today's intensive care units. The evidence that endogenous mediators actually mediate the individual's response to infection has led to various approaches to assess the individual's contribution to the course of the disease. The role of an individual's genetic background and predisposition for the extent of inflammatory responses is determined by variabilities of genes encoding endogenous mediators that constitute the pathways of inflammation. Primary responses in inflammation are mediated by proinflammatory cytokines such as tumor necrosis factor and interleukin 1. Conversely, anti-inflammatory mediators are released and may induce a state of immunosuppression in sepsis. Pro- and anti-inflammatory responses contribute to the outcome of patients with systemic inflammation and sepsis. Therefore, all genes encoding proteins involved in the transduction of inflammatory processes are candidate genes to determine the human genetic background that is responsible for interindividual differences in systemic inflammatory responses to injury. The genetically determined capacity of cytokine production and release, heat shock protein expression, nitric oxide synthase activity, gene polymorphisms of coagulation factors or factors of the innate immune system-like defensins, and other genes involved in inflammation may contribute to a wide range of clinical manifestations of an inflammatory disease. Genomic information may be used to identify groups of patients with a high risk of developing severe sepsis and multiple organ dysfunction, and determining which patients will benefit from antimediator strategies because of their genetic determination to high cytokine release in the inflammatory response will be the subject of future trials.
Effects of liraglutide in the treatment of obesity: a randomised, double-blind, placebo-controlled study
Authors: Arne Astrup, Stephan Rössner, Luc Van Gaal, Aila Rissanen, Leo Niskanen, Mazin Al Hakim, Jesper Madsen, Mads F Rasmussen, Michael Ej Lean
Journal: The Lancet (2009)
Cytokeratin-19 mRNA-Positive Circulating Tumor Cells After Adjuvant Chemotherapy in Patients With Early Breast Cancer
Authors: Nikolaos Xenidis, Michail Ignatiadis, Stella Apostolaki, Maria Perraki, Kostas Kalbakis, Sofia Agelaki, Efstathios N. Stathopoulos, Grigorios Chlouverakis, Evi Lianidou, Stylianos Kakolyris, Vassilis Georgoulias, Dimitris Mavroudis
Journal: Journal of Clinical Oncology (2009)

Purpose To evaluate the prognostic significance of cytokeratin-19 (CK-19) mRNA-positive circulating tumor cells (CTCs) in peripheral blood of women with early-stage breast cancer after the completion of adjuvant chemotherapy. Patients and Methods Blood was obtained from 437 patients with early breast cancer before the start and after the completion of adjuvant chemotherapy, and the presence of CK-19 mRNA-positive CTCs was assessed by real-time reverse transcriptase polymerase chain reaction. Interaction with known prognostic factors and association of CTCs with clinical outcome were investigated. Results CK-19 mRNA-positive CTCs were detected before chemotherapy in 179 patients (41.0%). After adjuvant chemotherapy, a significant change in CK-19 status was observed, as status for 51% of patients with initially CK-19 mRNA-positive disease turned negative, and status for 22% of patients with initially CK-19 mRNA-negative disease became positive (McNemar test P = .004). The detection of CK-19 mRNA-positive CTCs postchemotherapy was associated with involvement of more than three axillary lymph nodes (P = .026). Clinical relapses and disease-related deaths were significantly increased in patients with detectable postchemotherapy CK-19 mRNA-positive CTCs (both P &lt; .001, respectively). Disease-free and overall survival were significantly reduced in patients with detectable CK-19 mRNA-positive CTCs postchemotherapy (P &lt; .001 and P = .001, respectively). In multivariate analysis, the detection of CK-19 mRNA-positive CTCs before and after adjuvant chemotherapy was an independent factor associated with reduced disease-free survival (P &lt; .001) and overall survival (P = .003). Conclusion The detection of CK-19 mRNA-positive CTCs in the blood after adjuvant chemotherapy is an independent risk factor indicating the presence of chemotherapy-resistant residual disease.
Peripheral Administration of the Melanocortin-4 Receptor Antagonist NBI-12i Ameliorates Uremia-Associated Cachexia in Mice
Authors: Wai W. Cheung, Huey-Ju Kuo, Stacy Markison, Chen Chen, Alan C. Foster, Daniel L. Marks, Robert H. Mak
Journal: Journal of the American Society of Nephrology (2007)

We have recently shown that genetic or pharmacological blockade of the melanocortin-4 receptor (MC4-R) attenuates uremia-associated cachexia. However, the potential clinical utility of this approach has been limited by the need to deliver a peptide MC4-R antagonist into the ventricles of the brain. NBI-12i is a recently developed small molecule MC4-R antagonist, with high affinity and selectivity that penetrates the central nervous system after peripheral administration. We tested whether NBI-12i would also be effective in attenuating uremia-associated cachexia in a mouse model. Intraperitoneal administration of NBI-12i stimulated food intake and weight gain in uremic mice. Furthermore, NBI-12i-treated uremic mice gained lean body mass, fat mass, and had a lower basal metabolic rate compared to vehicle-treated and diet-supplemented uremic mice, which lost both lean body mass and fat mass and had an increase in basal metabolic rate. We found that NBI-12i normalizes the expression of uncoupling protein, which is normally upregulated in uremic mice, and we speculate that this may contribute to the drug's protective effect. These data underscore the importance of melanocortin signaling in the pathogenesis of uremia-associated cachexia and demonstrate the potential of peripheral administration of MC4-R antagonists as a novel therapeutic approach.
A phase I trial of erlotinib in patients with nonprogressive glioblastoma multiforme postradiation therapy, and recurrent malignant gliomas and meningiomas
Authors: J. J. Raizer, L. E. Abrey, A. B. Lassman, S. M. Chang, K. R. Lamborn, J. G. Kuhn, W.K. A. Yung, M. R. Gilbert, K. D. Aldape, P. Y. Wen, H. A. Fine, M. Mehta, L. M. DeAngelis, F. Lieberman, T. F. Cloughesy, H. I. Robins, J. Dancey, M. D. Prados
Journal: Neuro-Oncology (2009)

The objective of this phase I study was to determine the maximal tolerated dose (MTD) of erlotinib in patients with recurrent malignant gliomas (MGs) or recurrent meningiomas on enzyme-inducing antiepileptic drugs (EIAEDs). Dose escalation was by a standard 3 × 3 design. The initial starting dose of erlotinib was 150 mg daily. If no dose-limiting toxicity (DLT) was observed, then dose escalation occurs as follows: 200 mg/day, 275 mg/day, and then increased in 125 mg increments until the MTD was reached. The MTD was defined as the dose where ≤1 of 6 patients experienced a DLT and the dose above had 2 or more DLTs. The MTD was 650 mg/day; the observed DLTs were grade 3 rash in 2 patients at 775 mg/day. Pharmacokinetic analysis showed a significant influence of EIAEDs on the metabolism of erlotinib when compared with our phase II data published separately. Primary toxicities were rash and diarrhea. The MTD of erlotinib in patients receiving EIAEDs is substantially higher than the standard dose of 150 mg. This has important implications for further development of this drug in the treatment of MG as well as the optimal management of patients with other malignancies such as NSCLC who are on enzyme-inducing drugs.
Reproduction and Immunity-Driven Natural Selection in the Human WFDC Locus
Authors: Zélia Ferreira, Susana Seixas, Aida M. Andrés, Warren W. Kretzschmar, James C. Mullikin, Praveen F. Cherukuri, Pedro Cruz, Willie J. Swanson, Andrew G. Clark, Eric D. Green, Belen Hurle
Journal: Molecular Biology and Evolution (2013)

The whey acidic protein (WAP) four-disulfide core domain (WFDC) locus located on human chromosome 20q13 spans 19 genes with WAP and/or Kunitz domains. These genes participate in antimicrobial, immune, and tissue homoeostasis activities. Neighboring SEMG genes encode seminal proteins Semenogelin 1 and 2 (SEMG1 and SEMG2). WFDC and SEMG genes have a strikingly high rate of amino acid replacement (dN/dS), indicative of responses to adaptive pressures during vertebrate evolution. To better understand the selection pressures acting on WFDC genes in human populations, we resequenced 18 genes and 54 noncoding segments in 71 European (CEU), African (YRI), and Asian (CHB + JPT) individuals. Overall, we identified 484 single-nucleotide polymorphisms (SNPs), including 65 coding variants (of which 49 are nonsynonymous differences). Using classic neutrality tests, we confirmed the signature of short-term balancing selection on WFDC8 in Europeans and a signature of positive selection spanning genes PI3, SEMG1, SEMG2, and SLPI. Associated with the latter signal, we identified an unusually homogeneous-derived 100-kb haplotype with a frequency of 88% in Asian populations. A putative candidate variant targeted by selection is Thr56Ser in SEMG1, which may alter the proteolytic profile of SEMG1 and antimicrobial activities of semen. All the well-characterized genes residing in the WDFC locus encode proteins that appear to have a role in immunity and/or fertility, two processes that are often associated with adaptive evolution. This study provides further evidence that the WFDC and SEMG loci have been under strong adaptive pressure within the short timescale of modern humans.
High activity and reduced neurotoxicity of bi-fractionated oxaliplatin plus 5-fluorouracil/leucovorin for elderly patients with advanced colorectal cancer
Authors: R. Mattioli, C. Massacesi, F. Recchia, F. Marcucci, C. Cappelletti, L. Imperatori, A. Pilone, M. Rocchi, A. Cesta, G. Laici, M. Bonsignori, P. Lippe
Journal: Annals of Oncology (2005)
Direct intramyocardial plasmid vascular endothelial growth factor-A165gene therapy in patients with stable severe angina pectoris
Authors: Jens Kastrup, Erik Jørgensen, Andreas Rück, Kristina Tägil, Dietmar Glogar, Witold Ruzyllo, Hans Erik Bøtker, Dariusz Dudek, Viktor Drvota, Birger Hesse, Leif Thuesen, Pontus Blomberg, Mariann Gyöngyösi, Christer Sylvén
Journal: Journal of the American College of Cardiology (2005)
Peripheral Intravenous Cannulation
Authors: Rafael Ortega, Pavan Sekhar, Michael Song, Christopher J Hansen, Lauren Peterson
Journal: New England Journal of Medicine (2008)

Peripheral Intravenous Cannulation Introduction The ability to obtain peripheral intravenous access is an essential skill for all physicians. Although considered one of the simplest invasive procedures, mastering this potentially lifesaving intervention requires refined skills and experience. Cannulating a vein, particularly a small one, can be challenging. The purpose of this video is to demonstrate how to access peripheral veins using an intravenous catheter. Indications Peripheral intravenous catheterization is required in a broad range of clinical applications, including intravenous drug administration, for intravenous hydration, transfusions of blood or blood components, during surgery, during emergency care, and in other situations in which . . . .
Gastro-oesophageal reflux and aspiration of gastric contents in adult patients with cystic fibrosis
Authors: K Blondeau, L J Dupont, V Mertens, G Verleden, A Malfroot, Y Vandenplas, B Hauser, D Sifrim
Journal: Gut (2008)

<h3>Background:</h3> Gastro-oesophageal reflux (GOR) is increased in cystic fibrosis (CF), but its prevalence, characteristics, association with gastric aspiration and respiratory impact are not well characterised. We investigated acid and weakly acidic reflux, aspiration and respiratory symptoms/function in adult CF patients. <h3>Methods:</h3> Thirty-three CF patients [19 men; 29 (18–55) years, [10 post-lung transplant (LTx)] underwent impedance–pH monitoring for detection of acid (pH&lt;4) and weakly acid GOR (pH 4–7). In 16 patients cough was objectively recorded with oesophageal manometry, and the symptom association probability (SAP) was calculated. Saliva and bronchoalveolar lavage fluid (BALF) were tested for bile acids. <h3>Results:</h3> Twenty-eight patients had increased GOR (21 acid, 5 weakly acidic and 2 acid+weakly acidic) and 10 had a positive SAP for reflux cough. GOR parameters were similar in non-LTx and post-LTx CF patients. The sequence reflux cough was significantly more common than cough reflux. Sixteen of 38 patients had bile acids in saliva and 6/10 in BALF and this was almost exclusively observed in patients with genotype DF508/DF508. Only 12/28 with increased GOR and 9/22 with bile acids in saliva/BALF had typical reflux symptoms. There was a positive correlation (r = 0.53, p = 0.03) between oesophageal acid exposure and cough. SAP-positive patients with for reflux cough had a lower lung function than SAP-negative patients. <h3>Conclusion:</h3> Increased GOR is prevalent in CF and not secondary to cough. Acid GOR is common, but weakly acidic GOR may also occur. CF patients have a high risk of aspiration and reflux seems to be associated with more cough and poorer lung function. Outcome studies with intense anti-reflux therapy are needed to confirm the deleterious role of reflux in CF progression.