tbuckley/cabot-search huggingface dataset:
A Randomized, Blinded, Prospective Trial to Compare the Safety and Efficacy of Three Bowel-Cleansing Solutions for Colonoscopy (HSG-01*)
Authors: C. Ell, W. Fischbach, R. Keller, M. Dehe, G. Mayer, B. Schneider, U. Albrecht, W. Schuette
Journal: Endoscopy (2003)

Background and Study Aims: There are conflicting data regarding the optimal bowel preparation for colonoscopy. This study was carried out to compare the efficacy, safety, and tolerability of three widely used bowel lavage solutions: the standard polyethylene glycol-electrolyte solution based on the GoLytely formulation (PEG-EL1; Klean-Prep); a sulphate-free PEG-EL solution based on the NuLytely formulation (PEG-EL2, Endofalk); and a sodium phosphate preparation (NaP, Fleet Phospho-Soda). Patient and Methods: A total of 185 consecutive patients scheduled for elective colonoscopy were prospectively randomly assigned to undergo pre-colonoscopic bowel cleansing with either 4 l of PEG-EL1 (n = 64), 3 l of PEG-EL2 (n = 59), or 90 ml of NaP (n = 62). The quality of preparatory colonic cleansing for each segment from the rectum to the ascending colon was scored on a five-level rating scale (1, very good to 5, very poor) by endoscopists who were blinded with regard to the type of preparation used. The primary outcome measure for the comparison of treatments was the “worst” score in any of the rated bowel segments. Safety and tolerability were evaluated by means of a symptom questionnaire completed by each patient immediately before the procedure. Results: Of the 185 patients who were randomly assigned to one of the three treatments, 175 underwent colonoscopy and 173 were evaluable with regard to efficacy - 59, 54, and 60 patients treated with PEG-EL1, PEG-EL2, and NaP, respectively. The treatment groups were comparable with regard to the baseline characteristics. PEG-EL1 was statistically significantly superior to the other treatments in relation to the “worst cleansing” score (P ≤ 0.003). In addition, colonoscopic visualization was markedly better in each of the five bowel segments and general “very good” or “good” ratings were achieved in more than 90 % of patients treated with PEG-EL1. The percentages were consistently lower in the other two groups, particularly in the ascending colon. With the exception of the sigmoid, the differences in all segments of the large bowel were statistically significant (P ≤ 0.04). Patient satisfaction was comparable between the treatment groups. Adverse events (mainly nausea/vomiting and abdominal pain) and deviations in laboratory values occurred more frequently in the NaP group. Conclusions: Preparatory PEG-EL1 (Klean-Prep) was significantly superior to PEG-EL2 (Endofalk) and NaP (Fleet Phospho-Soda) in achieving effective cleansing of the entire colon prior to colonoscopy. On the basis of these data, PEG-EL1 can be regarded as the “gold standard” for bowel cleansing prior to colonoscopy.
Selective Generation of Gut Tropic T Cells in Gut-associated Lymphoid Tissue (GALT)
Authors: Bengt Johansson-Lindbom, Marcus Svensson, Marc-André Wurbel, Bernard Malissen, Gabriel Márquez, William Agace
Journal: The Journal of Experimental Medicine (2003)

In the current study, we address the underlying mechanism for the selective generation of gut-homing T cells in the gut-associated lymphoid tissues (GALT). We demonstrate that DCs in the GALT are unique in their capacity to establish T cell gut tropism but in vivo only confer this property to T cells in the presence of DC maturational stimuli, including toll-like receptor-dependent and -independent adjuvants. Thus, DCs from mesenteric LNs (MLNs), but not from spleen, supported expression of the chemokine receptor CCR9 and integrin α4β7 by activated CD8+ T cells. While DCs were also required for an efficient down-regulation of CD62L, this function was not restricted to MLN DCs. In an adoptive CD8+ T cell transfer model, antigen-specific T cells entering the small intestinal epithelium were homogeneously CCR9+α4β7+CD62Llow, and this phenotype was only generated in GALT and in the presence of adjuvant. Consistent with the CCR9+ phenotype of the gut-homing T cells, CCR9 was found to play a critical role in the localization of T cells to the small intestinal epithelium. Together, these results demonstrate that GALT DCs and T cell expression of CCR9 play critical and integrated roles during T cell homing to the gut.
IMMUNOGLOBULIN AND GLUCOSE-6-PHOSPHATE DEHYDROGENASE AS MARKERS OF CELLULAR ORIGIN IN BURKITT LYMPHOMA
Authors: Philip J. Fialkow, Eva Klein, George Klein, Peter Clifford, Surjit Singh
Journal: The Journal of Experimental Medicine (1973)

Two independent marker systems, G-6-PD isoenzymes and cell membrane-associated IgM, were used to trace the cellular origin of Burkitt lymphoma. Application of the G-6-PD system is dependent upon the fact that, in accordance with inactivity of one X chromosome in each somatic cell, females heterozygous for the usual B gene (Gd(B)) at the X-linked G-6-PD locus and the variant allele Gd(A) (or Gd(A-)) have two types of cells. Gd(B) is active in one cell population, which consequently produces B type enzyme; in the other population Gd(A) is active, producing the variant A enzyme. Therefore, tumors with a clonal origin in a Gd(B)/Gd(A) heterozygote should exhibit only one enzyme type (B or A) whereas those with multicellular origin may show both A and B enzymes. Utilization of the immunoglobulin system is based upon the supposition that in lymphoid neoplasms with clonal origin either all or none of the tumor cells should have surface-associated IgM and kappa-reactivities. 33 of 34 relatively homogeneous (with respect to content of neoplastic cells) individual Burkitt tumors from 19 G-6-PD heterozygotes had single enzyme phenotypes. Similarly, of 95 tumors tested, 92 consisted essentially of IgM(+) or (-) cells. Two neoplasms could not be definitely classified and one tumor had two cell populations. These data suggest a clonal origin for most Burkitt tumors, but the one neoplasm with a double G-6-PD phenotype (A/B) and the one tumor that had two populations of cells with respect to surface IgM, could have originated from multiple cells. G-6-PD was determined in each of two tumors from seven heterozygotes and in all cases both tumors had the same single enzyme phenotype. Surface-associated IgM was tested in four tumors from one patient, three from another, and in two neoplasms from 11 patients. With one exception, all tumors from the same patient were concordant with respect to IgM. These findings suggest that the entire disease has a clonal origin, i.e., it emerges at one focus and then spreads to other parts of the body. Cells from 36 recurrent neoplasms were typed for G-6-PD (in heterozygotes) and/or IgM. In one previously reported patient, initial and recurrent tumors were discordant for G-6-PD. Two other patients had IgM phenotypes in recurrences that were discordant with those found in their initial tumors. Phenotypes from three of nine relapses which occurred after 5 mo were discordant for G-6-PD or IgM but no discordance was detected among 27 earlier recurrences. Thus, some "late" recurrences may be due to emergence of "new" maligant cell lines whereas most early relapses are due to reemergence of the original malignant clones. The probable unicellular origin of Burkitt lymphoma and the findings in tumor recurrences are discussed in terms of the disease's putative viral etiology.
Paediatric home nursing scheme in Gateshead.
Authors: M R Hally, A Holohan, R H Jackson, B L Reedy, J H Walker
Journal: BMJ (1977)

A scheme to provide specialised nursing care for sick children in their own homes was begun in Gateshead in 1974. Selected district nurses were retrained in the paediatric unit on which the scheme was based and nursed at home 22 children referred to them by general practitioners as the alternative to hospital admission and 39 discharged to their care by the hospital. Most of the children were aged 3 years or less and came from working-class homes. Most of the mothers who were asked were in favour of the scheme.
Cimetidine in patients with gastric ulcer: a multicentre controlled trial.
Authors: F Frost, I Rahbek, S J Rune, K B Jensen, E Gudmand-Hoyer, E Krag, J Rask-Madsen, H R Wulff, J Garbol, K G Jensen, M Hojlund, V R Nissen
Journal: BMJ (1977)

Forty-five adult outpatients with endoscopically confirmed gastric ulceration completed a double-blind trial of either cimetidine (1 g/day) or placebo. After six weeks 18 of the 23 patients receiving cimetidine showed complete ulcer healing compared with only six of the 22 patients receiving placebo. The cimetidine group also had fewer days with pain than the placebo group but the difference was not statistically significant. Cimetidine therefore seems to promote healing of gastric ulcers without severe side effects, although its effect on pain is less pronounced than in patients with duodenal ulcers.
Abstract 762: Prevention and reversion of multidrug resistance (MDR) in cancer by NSC23925
Authors: Xiaoqian Yang, Francis Hornicek, Zhenfeng Duan
Journal: Cancer Research (2014)

Abstract The major limitation to the success of chemotherapy in cancer is the development of multidrug resistance (MDR). Preventing the emergence of MDR during chemotherapy treatment has been a high priority of clinical and investigational oncology, but remains an elusive goal. NSC23925 has recently been identified as a novel and potent MDR reversal agent. However, whether NSC23925 can prevent the development of MDR in cancer is unknown. Therefore, this study was to evaluate the effects of NSC23925 on prevention and reversion of MDR. Human osteosarcoma cell line U-2OS and Saos were exposed to increasing concentrations of taxol alone or in combination with NSC23925 for 6 months. The results showed that cells selected with increasing concentrations of taxol alone developed MDR with resistance to taxol and other Pgp substrates, while cells cultured with taxol-NSC23925 simultaneously prevented the development of MDR and cells remained sensitive to chemotherapeutic agents. Taxol selected resistant cells showed high expression and activity of drug transporter P-glycoprotein (Pgp), whereas taxol-NSC23925 combination treatment prevented the expression of Pgp. Our findings suggest that NSC23925 may prevent the development of MDR by specifically preventing the overexpression of Pgp. Moreover, NSC23925 can reverse MDR in drug resistant cells by modulating Pgp activity. Given the significant incidence of MDR in cancer and the lack of effective agents for prevention and revision of MDR, NSC23925 and derivatives hold the potential to improve the outcome of cancer patients with poor prognosis due to drug resistance. Citation Format: Xiaoqian Yang, Francis Hornicek, Zhenfeng Duan. Prevention and reversion of multidrug resistance (MDR) in cancer by NSC23925. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 762. doi:10.1158/1538-7445.AM2014-762
The General Medical Journal: For Readers or Repositories?
Authors: Franz J. Ingelfinger
Journal: New England Journal of Medicine (1977)

Abstract General medical journals seek newsworthiness but face obstacles because of their usually slow publication schedules and because of contents that readers find either obscure or contradictory to long held beliefs. In addition, since medical news has become "big news," general medical journals find themselves in competition with both the lay press and the medical giveaways. One effect of the escalating public interest in medical news is that general medical journals that are reliable and have maintained their newsworthiness are increasingly cited. These journals thus eventually transmit research findings to the public as well as to the health-care professions. To help prevent exaggeration and misinterpretation by the lay press and by the public, general medical journals must evaluate submissions in a broader than traditional context. Nevertheless, newsworthiness is an appropriate goal for such journals. (N Engl J Med 296:1258–1264, 1977)
A Novel Interpretation of Structural Dot Plots of Genomes Derived from the Analysis of Two Strains of Neisseria meningitidis
Authors: Wilfred R. Cuff, Venkata R.S.K. Duvvuri, Binhua Liang, Bhargavi Duvvuri, Gillian E. Wu, Jianhong Wu, Raymond S.W. Tsang
Journal: Genomics Proteomics & Bioinformatics (2010)

Abstract Neisseria meningitidis is the agent of invasive meningococcal disease, including cerebral meningitis and septicemia. Because the diseases caused by different clonal groups (sequence types) have their own epidemiological characteristics, it is important to understand the differences among the genomes of the N. meningitidis clonal groups. To this end, a novel interpretation of a structural dot plot of genomes was devised and applied; exact nucleotide matches between the genomes of N. meningitidis serogroup A strain Z2491 and serogroup B strain MC58 were identified, leading to the specification of various structural regions. Known and putative virulence genes for each N. meningitidis strain were then classified into these regions. We found that virulence genes of MC58 tend more to the translocated regions (chromosomal segments in new sequence contexts) than do those of Z2491, notably tending towards the interface between one of the translocated regions and the collinear region. Within the collinear region, virulence genes tend to occur within 16 kb of gaps in the exact matches. Verification of these tendencies using genes clustered in the cps locus was sufficiently supportive to suggest that these tendencies can be used to focus the search for and understanding of virulence genes and mechanisms of pathogenicity in these two organisms.
Is right bundle branch block aviodable in surgical correction of tetralogy of Fallot?
Authors: E Hazan, O Bical, J P Bex, C Dubuis, Y Lecompte, C De Riberolles, J Y Neveux
Journal: Circulation (1980)

Right bundle branch block (RBBB) is usually considered almost unaviodable after repair of teralogy of Fallot (TOF). By modifications of the standard technique, its frequency has been decreased to 32% in a series of 1000 consecutive patients. These modifications are: (1) a very short right ventricular incision avoiding the ventriculotomy-induced RBBB pattern; (2) an infundibular resection limited to the septal attachment of the infundibular septum; and (3) closure of the ventricular septal defect with a patch sutured to the very edge of the muscular septum, avoiding injury to the right bundle along the right aspect of the septum. No patient in this series sustained permanent complete atrioventricular heart block. Among patients with RBBB, five had a left anterior hemiblock. Postoperative intraventricular conduction was related to age at operation: The incidence of RBBB was significatively higher in infants. The beneficial effects of a low incidence of postoperative RBBB after repair of TOF are not known.
Organic Acids in Ethylene Glycol Intoxication
Authors: PATRICIA A. GABOW
Journal: Annals of Internal Medicine (1986)

Ethylene glycol intoxication produces a severe metabolic acidosis with an increased anion gap. We examined three patients with this intoxication to identify the organic acids that cause acidemia in humans and to determine how effectively these acids can be removed during dialysis. All patients had markedly elevated glycolic acid levels of more than 7 meq/L and two patients had lactic acidosis, with lactic acid levels of greater than 5.0 meq/L. Hemodialysis clearance of glycolic acid was 105 mL/min, and 159 meq was removed in 3 hours. After hemodialysis using a bicarbonate dialysate, the mean anion gap decreased from 34 to 23 meq/L; the mean serum bicarbonate concentration increased from 5.5 to 20 meq/L. Therefore, glycolic and lactic acids are important in the acidosis caused by ethylene glycol intoxication in humans. Hemodialysis treatment with a bicarbonate dialysate is an efficient method for removing glycolic acid and resolving acidemia.
Young Montgomery and His Beating Heart
Authors: Henry R. Viets
Journal: New England Journal of Medicine (1957)

Dr. J. C. White has called my attention to an unusual clinical description of a young man who had lost the anterior portion of his chest by accident, and thus carried an open window to the heart where the organ could be seen in action and even palpated. This observation, by William Harvey, is tucked away in his book on Generation of Living Creatures, first published in Latin in London in 1651. The case record occurs at a point where Harvey is considering blood, sensation and the various parts of the body. Apparently, there was a physiologic discussion in . . .
Combined DOCK8 and CLEC7A mutations causing immunodeficiency in 3 brothers with diarrhea, eczema, and infections
Authors: Darrell L. Dinwiddie, Stephen F. Kingsmore, Sonia Caracciolo, Giuseppe Rossi, Daniele Moratto, Cinzia Mazza, Cristiano Sabelli, Rosa Bacchetta, Laura Passerini, Chiara Magri, Callum J. Bell, Neil A. Miller, Shannon L. Hateley, Carol J. Saunders, Lu Zhang, Gary P. Schroth, Sergio Barlati, Raffaele Badolato
Journal: Journal of Allergy and Clinical Immunology (2013)
The cyclophilin inhibitor alisporivir prevents hepatitis C virus-mediated mitochondrial dysfunction
Authors: Giovanni Quarato, Annamaria D'Aprile, Bruno Gavillet, Grégoire Vuagniaux, Darius Moradpour, Nazzareno Capitanio, Claudia Piccoli
Journal: Hepatology (2011)

Alisporivir (Debio-025) is an analogue of cyclosporine A and represents the prototype of a new class of non-immunosuppressive cyclophilin inhibitors. In vitro and in vivo studies have shown that alisporivir inhibits hepatitis C virus (HCV) replication, and ongoing clinical trials are exploring its therapeutic potential in patients with chronic hepatitis C. Recent data suggest that the antiviral effect is mediated by inhibition of cyclophilin A, which is an essential host factor in the HCV life cycle. However, alisporivir also inhibits mitochondrial permeability transition by binding to cyclophilin D. Because HCV is known to affect mitochondrial function, we explored the effect of alisporivir on HCV protein-mediated mitochondrial dysfunction. Through the use of inducible cell lines, which allow to investigate the effects of HCV polyprotein expression independent from viral RNA replication and which recapitulate the major alterations of mitochondrial bioenergetics observed in infectious cell systems, we show that alisporivir prevents HCV protein-mediated decrease of cell respiration, collapse of mitochondrial membrane potential, overproduction of reactive oxygen species and mitochondrial calcium overload. Strikingly, some of the HCV-mediated mitochondrial dysfunctions could even be rescued by alisporivir.These observations provide new insights into the pathogenesis of HCV-related liver disease and reveal an additional mechanism of action of alisporivir that is likely beneficial in the treatment of chronic hepatitis C.
A Comparison of the Opinions of Experts and Readers as to What Topics a General Medical Journal (&lt;EMPH&gt;JAMA&lt;/EMPH&gt;) Should Address
Authors: George D. Lundberg
Journal: JAMA (1998)

Context.—Journal editors are responsible to many publics, and their choices of articles to publish are a frequent source of dispute.Objective.—To assess the extent of agreement between topics identified by experts and by JAMA readers as most important for publication.Design and Participants.—Modified Delphi process of polling of JAMA Editorial Board members and senior staff (ie, experts) in 1996, and masked direct mail survey of a stratified sample of JAMA readers in late 1996 and early 1997.Main Outcome Measures.—Agreement between experts and readers on the topics most important for JAMA to deal with in 1997.Results.—Of 55 experts polled, the 40 respondents (73% response rate) proposed 178 topics. Editing to combine similar topics left 73. The same 55 persons were asked to stratify all 73 alphabetically arranged topics on a scale of 1 to 5 (85% [47/55] response rate). They were then given the results of this ballot and asked to vote again (76% [42/55] response rate). Of the 55 experts, 40 attending the annual editorial board meeting were given all results; 39 attendees voted on the final topics. In response to the mail survey, a single pass of the same 73 topics yielded a response rate of 41.6% (208 returns). Nonresponders were roughly equivalent to responders demographically. Readers agreed with the experts on only 3 of the top 10 subjects: managed care, cancer, and aging.Conclusion.—Expert opinion and the opinion of readers as to what JAMA should emphasize vary widely.
Outpatient Antibiotic Therapy for Osteomyelitis-Reply
Authors: John M. Eisenberg
Journal: JAMA (1987)

<h3>In Reply.—</h3> We sympathize with Drs Cohen and Weber's concern that physicians may rely inappropriately on a single scientific report in changing their practices. However, they may have misinterpreted the message of our report on potential savings from outpatient treatment of osteomyelitis. We presented the use of cefonicid as an<i>example</i>of a drug with which "earlydischarge therapy... may be enhanced." Based on the report by Kunkel and Iannini,<sup>1</sup>as well as the submission of data for the drug's approval, we came to the same conclusion as the Food and Drug Administration—that cefonicid is an appropriate drug for treatment of many cases of osteomyelitis. Our economic analysis assumed that drug therapy would be started in the hospital and clinical response demonstrated before discharge for outpatient antibiotic therapy. Others have reached similar conclusions, including the authors of a comprehensive review of cefonicid,<sup>2</sup>who wrote that "patients who require prolonged
Desmolaris, a novel factor XIa anticoagulant from the salivary gland of the vampire bat (Desmodus rotundus) inhibits inflammation and thrombosis in vivo
Authors: Dongying Ma, Daniella M. Mizurini, Teresa C. F. Assumpção, Yuan Li, Yanwei Qi, Michail Kotsyfakis, José M. C. Ribeiro, Robson Q. Monteiro, Ivo M. B. Francischetti
Journal: Blood (2013)

The identity of vampire bat saliva anticoagulant remained elusive for almost a century. Sequencing the salivary gland genes from the vampire bat Desmodus rotundus identified Desmolaris as a novel 21.5-kDa naturally deleted (Kunitz 1-domainless) form of tissue factor pathway inhibitor. Recombinant Desmolaris was expressed in HEK293 cells and characterized as a slow, tight, and noncompetitive inhibitor of factor (F) XIa by a mechanism modulated by heparin. Desmolaris also inhibits FXa with lower affinity, independently of protein S. In addition, Desmolaris binds kallikrein and reduces bradykinin generation in plasma activated with kaolin. Truncated and mutated forms of Desmolaris determined that Arg32 in the Kunitz-1 domain is critical for protease inhibition. Moreover, Kunitz-2 and the carboxyl-terminus domains mediate interaction of Desmolaris with heparin and are required for optimal inhibition of FXIa and FXa. Notably, Desmolaris (100 μg/kg) inhibited FeCl3-induced carotid artery thrombus without impairing hemostasis. These results imply that FXIa is the primary in vivo target for Desmolaris at antithrombotic concentrations. Desmolaris also reduces the polyphosphate-induced increase in vascular permeability and collagen- and epinephrine-mediated thromboembolism in mice. Desmolaris emerges as a novel anticoagulant targeting FXIa under conditions in which the coagulation activation, particularly the contact pathway, plays a major pathological role.