tbuckley/cabot-search huggingface dataset:
Endoscopic extraction of bile duct stones: management related to stone size.
Authors: A Lauri, R C Horton, B R Davidson, A K Burroughs, J S Dooley
Journal: Gut (1993)

Endoscopic sphincterotomy has become the first line treatment for patients with common bile duct (CBD) stones. This technique may fail, however, due to difficult anatomy, previous surgery, periampullary diverticula or the presence of a large stone. The importance of stone size to the success of endoscopic sphincterotomy has not been fully assessed. A prospective study was carried out over the period January 1987 to December 1989 on 100 patients (45 male, 55 female, median age 69 years, range 19-97) with CBD stones in which a policy of early duct clearance was followed. Endoscopic retrograde cholangiopancreatography (ERCP) was performed and the stone size and number recorded from the cholangiograms and corrected for magnification. Sphincterotomy was performed using a diathermy unit with a cutting current and stones were extracted using a balloon catheter or a Dormia basket. Of the 100 patients with CBD stones receiving ERCP, successful clearance of the biliary tree was possible in seven without endoscopic sphincterotomy and five were felt to be unsuitable for endoscopic sphincterotomy. Of the remaining 88 patients endoscopic sphincterotomy was successful in 75 (85%). Of the 75 patients having endoscopic sphincterotomy stone clearance was successful in 44 (59%). There were no deaths and only four complications, which rapidly resolved on conservative treatment (two acute pancreatitis, two bleeding). The number of CBD stones present was similar in those patients with successful endoscopic sphincterotomy and duct clearance (median 1, range 1-10, n = 44) as in those in whom it failed (median 2, range 1-6, n = 31). In contrast there was a highly significant difference when stone size was analysed (successful clearance median stone size 10 mm, range 3-27 mm; unsuccessful: median 18 mm, range 10-42, p<0.001). Stones less than 10 mm in diameter (n=21) were all removed successfully whereas in patients with stones over 15 mm (n=25) only three were removed endoscopically (12%). All patients with evidence of residual stones had additional treatment. Of these 31 patients, 10 had surgery, 11 had insertion of an endoprosthesis, and 10 had dissolution treatment with methyl-tert-butyl ether through a nasobiliary catheter. This study shows the importance of stone size to the success rate of endoscopic removal of bile duct stones.
Investigating the Association Between Cigarette Smoking and Schizophrenia in a Cohort Study
Authors: Stanley Zammit, Peter Allebeck, Christina Dalman, Ingvar Lundberg, Tomas Hemmingsson, Glyn Lewis
Journal: American Journal of Psychiatry (2003)

OBJECTIVE: Many case-control and cross-sectional studies have observed an association with cigarette smoking after the onset of schizophrenia, and there is evidence to suggest that smoking may improve symptoms in people with this disorder. Here, the authors investigated whether cigarette smoking alters the risk of subsequently developing schizophrenia. No longitudinal studies have previously examined this relationship. METHOD: A cohort of 50,087 Swedish conscripts (98% were ages 18–20) was followed up by record linkage to the National Register of Inpatient Care from 1970 to 1996 to determine hospital admission for schizophrenia. Cox regression was used to obtain hazard ratios and 95% confidence intervals (CIs) for schizophrenia, according to smoking status. RESULTS: Smoking cigarettes at ages 18–20 was associated with a lower rate of developing schizophrenia after adjustment for confounders. There was a linear relationship between the number of cigarettes smoked and a lower risk of schizophrenia (adjusted hazard ratio for linear trend across smoking categories, 0.8 [95% CI=0.7–0.9]), with an adjusted hazard ratio for heavy smokers of 0.5 (95% CI=0.3–0.9) compared to that of nonsmokers. This association persisted when analysis was restricted to subjects diagnosed after the first 5 years following conscription to reduce possible prodromal effects of schizophrenia on smoking. CONCLUSIONS: Cigarette smoking may be an independent protective factor for developing schizophrenia. These results are consistent with animal models showing both neuroprotective effects of nicotine and differential release of prefrontal dopamine in response to nicotine. The harmful effects of cigarette smoking vastly outweigh any possible benefits, but nevertheless, further investigation may lead to important insights regarding the etiology of schizophrenia at a molecular level.
Predominant Gain of Promoter TATA Box after Gene Duplication Associated with Stress Responses
Authors: Yangyun Zou, Wei Huang, Zhenglong Gu, Xun Gu
Journal: Molecular Biology and Evolution (2011)

TATA box, the core promoter element, exists in a broad range of eukaryotes, and the expression of TATA-containing genes usually responds to various environmental stresses. Hence, the evolution of TATA-box in duplicate genes may provide some clues for the interrelationship among environmental stress, expression differentiation, and duplicate gene preservation. In the present study, we observed that the TATA box is significantly overrepresented in duplicate genes compared with singletons in human, worm, Arabidopsis, and yeast genomes. We then conducted an extensive functional genomic analysis to investigate the evolution of TATA box along over 700 yeast gene family phylogenies. After reconstructing the ancestral TATA-box states (presence or absence), we found that significantly higher numbers of TATA box gain events than loss events had occurred after yeast gene duplications—the overall gain–loss ratio is about 3–4 to 1. Interestingly, these TATA-gain duplicate genes on average have experienced greater expression divergence from the ancestral expression states than their most closely related TATA-less duplicate partners, but only under environmental stress conditions (asymmetric evolution); indeed, under normal physiological conditions, they have similar expression divergence (symmetric evolution). Moreover, we showed that TATA-gain duplicates are enriched in stress-associated functional categories but that is not the case for TATA-ancestral duplicates (those inherited from their ancestors prior to duplication). Together, we conclude that after the gene duplication, gain of the TATA box in duplicate promoters may have played an important role in yeast duplicate preservation by accelerating expression divergence that may facilitate the adaptive evolution of the organism in response to environmental changes.
Haplotype analysis in western European patients with mal de Meleda: founder effect for the W15R mutation in the<i>SLURP1</i>gene
Authors: R.G.L. Nellen, P.M. Steijlen, H.C. Hennies, J. Fischer, C.S. Munro, M.F. Jonkman, M.A.M. van Steensel, M. van Geel
Journal: British Journal of Dermatology (2013)

Journal Article Haplotype analysis in western European patients with mal de Meleda: founder effect for the W15R mutation in the SLURP1 gene Get access R.G.L. Nellen, R.G.L. Nellen Department of DermatologyGROW Research School for Oncology and Developmental Biology Search for other works by this author on: Oxford Academic Google Scholar P.M. Steijlen, P.M. Steijlen Department of DermatologyGROW Research School for Oncology and Developmental Biology Search for other works by this author on: Oxford Academic Google Scholar H.C. Hennies, H.C. Hennies Division of Dermatogenetics, Cologne Center for Genomics, University of Cologne, Cologne, Germany Search for other works by this author on: Oxford Academic Google Scholar J. Fischer, J. Fischer Institute of Human Genetics, University Medical Center Freiburg, Freiburg, Germany Search for other works by this author on: Oxford Academic Google Scholar C.S. Munro, C.S. Munro Alan Lyell Centre for Dermatology, Glasgow, U.K Search for other works by this author on: Oxford Academic Google Scholar M.F. Jonkman, M.F. Jonkman Department of Dermatology, University Medical Center Groningen, Groningen, The Netherlands Search for other works by this author on: Oxford Academic Google Scholar M.A.M. van Steensel, M.A.M. van Steensel Department of DermatologyGROW Research School for Oncology and Developmental BiologyClinical Genetics, Maastricht University Medical Centre, Maastricht University Medical Centre, PO Box 5800, 6202 AZ Maastricht, The Netherlands Search for other works by this author on: Oxford Academic Google Scholar M. van Geel M. van Geel Department of DermatologyClinical Genetics, Maastricht University Medical Centre, Maastricht University Medical Centre, PO Box 5800, 6202 AZ Maastricht, The Netherlands Michel van Geel. E‐mail: m.van.geel@mumc.nl Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 168, Issue 6, 1 June 2013, Pages 1372–1374, https://doi.org/10.1111/bjd.12203 Published: 01 June 2013
Adjuvant Therapy in the Treatment of Biliary Tract Cancer: A Systematic Review and Meta-Analysis
Authors: Anne M. Horgan, Eitan Amir, Thomas Walter, Jennifer J. Knox
Journal: Journal of Clinical Oncology (2012)

Purpose The benefit of adjuvant therapy (AT) for biliary tract cancer (BTC) is unclear, with conflicting results from nonrandomized studies. We report a systematic review and meta-analysis to determine the impact of AT on survival. Methods Studies published between 1960 and November 2010, which evaluated adjuvant chemotherapy (CT), radiotherapy (RT), or both (CRT) compared with curative-intent surgery alone for resected BTC were included. Only tumors of the gallbladder and bile ducts were assessed. Published data were extracted and computed into odds ratios (ORs) for death at 5 years. Subgroup analyses of benefit based on lymph node (LN) or resection margin positivity (R1) were prespecified. Data were weighted by generic inverse variance and pooled using random-effect modeling. Results Twenty studies involving 6,712 patients were analyzed. There was a nonsignificant improvement in overall survival with any AT compared with surgery alone (pooled OR, 0.74; P = .06). There was no difference between gallbladder and bile duct tumors (P = .68). The association was significant when the two registry analyses were excluded. Those receiving CT or CRT derived statistically greater benefit than RT alone (OR, 0.39, 0.61, and 0.98, respectively; P = .02). The greatest benefit for AT was in those with LN-positive disease (OR, 0.49; P = .004) and R1 disease (OR, 0.36; P = .002). Conclusion This analysis supports AT for BTC. Prospective randomized trials are needed to provide better rationale for this commonly used strategy. On the basis of our data, such trials could involve two active comparators rather than a no-treatment arm among patients with LN-positive or R1 disease.
PWE-284 Khat as a possible cause of drug induced autoimmune hepatitis; a case series
Authors: S Riyaz, M Imran, M Karajeh
Journal: Gut (2012)

<h3>Introduction</h3> Khat is well recognised for its hepatotoxic effects. The exact mechanism by which it causes liver damage remains unknown. We report a series of patients with a history of khat use presenting with acute hepatitis, and review the potential role of khat in triggering auto immune hepatitis (AIH). <h3>Methods</h3> The database at Sheffield Hospitals was searched for patients referred to the Hepatology department between 2005 and 2010 with liver problems and a history of khat use. They were then assessed for probability of having AIH using the revised criteria for diagnosis of AIH.<sup>1</sup> <h3>Results</h3> Six patients presenting with acute hepatitis on a background of khat use were identified. All of the patients were male. Five of these patients were of Somali origin, while one patient was from Yemen. The age range of these patients was 24–57 years (mean 42.3 years). The patients were scored according to the revised autoimmune hepatitis criteria. They were given minus four (−4) for khat use on the scoring system due to its potential hepatotoxicity. Despite this, five out of six patients had a pre treatment score of 10 to 15 which placed them in the probable group for autoimmune hepatitis. The five patients that were in the probable group had at least a partial response to corticosteroids with a greater than 50% reduction in their ALT after 1-month of treatment. The patient that had scored negative for AIH (&lt;10) showed the least improvement with prednisolone and continued to have raised liver enzymes after 1-year of treatment. <h3>Conclusion</h3> The exact mechanism by which khat causes hepatotoxicity remains elusive. One possibility could be by triggering autoimmune hepatitis in a genetically susceptible individual. Further studies are needed to evaluate this phenomenon.<sup>2 3</sup> <h3>Competing interests</h3> None declared. <h3>References</h3> 1. <b>Alvarez F</b>, <i>et al.</i> International Autoimmune Hepatitis Group Report: review of criteria for diagnosis of autoimmune hepatitis. <i>J Hepatol</i> 1999;<b>31</b>:929–38. 2. <b>Chapman MH</b>, Kajihara M, Borges G, <i>et al.</i> Severe, acute liver injury and khat leaves. <i>N Engl J Med</i> 2010;<b>362</b>:1642–4. 3. <b>Peevers CG</b>, Moorghen M, Collins PL, <i>et al.</i> Liver disease and cirrhosis because of Khat chewing in UK Somali men: a case series. <i>Liver Int</i> 2010.
Changing the Way We Think About Chronic Lymphocytic Leukemia
Authors: Thomas S. Lin, Michael R. Grever, John C. Byrd
Journal: Journal of Clinical Oncology (2005)

The treatment of chronic lymphocytic leukemia (CLL) has undergone a revolution during the past two decades. CLL was considered an indolent, incurable disease, and therapy consisted primarily of alkylator-based regimens. The introduction of the purine analogs fludarabine, pentostatin, and cladribine into clinical trials in the 1980s invigoratedclinicalresearchinCLLanddramaticallychanged the treatment of this disease. Studies using fludarabine as salvage therapy demonstrated that a small fraction (10% or less) of patients attained complete remission (CR), 1,2 whereasuptoathirdofpatientsattainedaCRwithfludarabine as first-line therapy. 3 Three large phase III trials in symptomatic, untreated CLL patients have confirmed the superiority offludarabine, demonstrating advantages in response rate, CR rate, and progression-free survival (PFS) compared with alkylator-based regimens. 4-6 However, no overallsurvival(OS)improvementwasnotedinthesestudies. A small incremental increase may not have been identified because of trial sample size or cross-over designs that allowed patients to receivefludarabine after progression on alkylator therapy. Given that we treat CLL at time of symptomsandgiventheabilityoffludarabinetomoreeffectively palliate disease-related manifestations and time of remission, fludarabine is considered by many, but not all, physicians as a better initial treatment than alkyators for CLL. Because of the ability of fludarabine to result in complete responses, this end point might serve as a surrogate marker for improved survival. This notion was derived from clinical experience in acute leukemia and nonHodgkin’s lymphoma (NHL), where CR correlates with long-term survival. In CLL, the relationship of CR to longtermsurvivalislessclear.Long-termfollow-upbytheM.D. Anderson group with fludarabine monotherapy did not confirm this, 7 and the randomized phase III studies of flu
Overall Survival After Concurrent Cisplatin-Radiotherapy Compared With Radiotherapy Alone in Locoregionally Advanced Nasopharyngeal Carcinoma
Authors: A. T. C. Chan, S. F. Leung, R. K. C. Ngan, P. M. L. Teo, W. H. Lau, W. H. Kwan, E. P. Hui, H. Y. Yiu, W. Yeo, F. Y. Cheung, K. H. Yu, K. W. Chiu, D. T. Chan, T. S. K. Mok, S. Yau, K. T. Yuen, F. K. F. Mo, M. M. P. Lai, B. B. Y. Ma, M. K. M. Kam, T. W. T. Leung, P. J. Johnson, P. H. K. Choi, B. C. Y. Zee
Journal: JNCI Journal of the National Cancer Institute (2005)

This phase III randomized study compared concurrent cisplatin–radiotherapy (CRT) versus radiotherapy (RT) alone in patients with locoregionally advanced nasopharyngeal carcinoma. A total of 350 patients were randomly assigned to receive external RT alone or concurrently with cisplatin at a dosage of 40 mg/m 2 weekly. The primary endpoint was overall survival, and the median follow-up was 5.5 years. The 5-year overall survival was 58.6% (95% confidence interval [CI] = 50.9% to 66.2%) for the RT arm and 70.3% (95% CI = 63.4% to 77.3%) for the CRT arm. In Cox regression analysis adjusted for T stage, age, and overall stage, the difference in overall survival was statistically significantly in favor of concurrent CRT ( P = .049, hazard ratio [HR] = 0.71 [95% CI = 0.5 to 1.0]). Subgroup analysis demonstrated that there was no difference between overall survival in the arms for T1/T2 stage ( P = .74, HR = 0.93 [95% CI = 0.59 to 1.4]), whereas there was a difference between the arms for T3/T4 stage ( P = .013, HR = 0.51 [95% CI = 0.3 to 0.88]), favoring the CRT arm. The regimen of weekly concurrent CRT is a promising standard treatment strategy for locoregionally advanced nasopharyngeal carcinoma patients.
GenoType MTBDR<i>sl</i> Line Probe Assay Shortens Time to Diagnosis of Extensively Drug-Resistant Tuberculosis in a High-Throughput Diagnostic Laboratory
Authors: Marinus Barnard, Rob Warren, Nico Gey Van Pittius, Paul van Helden, Marlein Bosman, Elizabeth Streicher, Gerrit Coetzee, Richard O’Brien
Journal: American Journal of Respiratory and Critical Care Medicine (2012)

Rationale: Conventional culture-based drug susceptibility testing (DST) for the second-line antituberculosis drugs is slow, leading to diagnostic delay with associated exacerbation of transmission, amplification of resistance, and increased mortality.Objectives: To assess the diagnostic performance of the GenoType MTBDRsl line probe assay (LPA) for the rapid detection of mutations conferring resistance to ofloxacin (OFX), amikacin (AMK), and ethambutol and to determine the impact of implementation on the turnaround time in a high-throughput diagnostic laboratory.Methods: Six hundred and fifty-seven direct patient acid-fast bacilli smear-positive specimens resistant to isoniazid, rifampin, or both according to the GenoType MTBDRplus assay were consecutively tested, using the GenoType MTBDRsl LPA. The diagnostic performance was assessed relative to the “gold standard” culture-based method, and the laboratory turnaround times for both methods were determined.Measurements and Main Results: A total of 516 of 657 patient specimens had valid results for both tests. The sensitivity for detecting OFX, AMK, and extensive drug resistance, using the GenoType MTBDRsl LPA, was 90.7% (95% confidence interval [CI], 80.1–96.0%), 100% (95% CI, 91.8–100%), and 92.3% (95% CI, 75.9–97.9%), respectively, and the specificity for detection was 98.1% (95% CI, 96.3–99.0%), 99.4% (95% CI, 98.2–99.8%), and 99.6% (95% CI, 98.5–99.9%), respectively. Implementation of this test significantly reduced the turnaround time by 93.3% (P < 0.001), calculated from the date that the specimen was received at the laboratory to reporting second-line results. In addition, a significant increase in diagnostic yield of 20.1% and 19.3% (P < 0.001) for OFX and AMK resistance, respectively, was obtained for isolates that were either contaminated or had lost viability.Conclusions: The GenoType MTBDRsl LPA is a rapid and reliable DST that can be easily incorporated into the diagnostic algorithm. This assay significantly improved diagnostic yield (P < 0.001) while simultaneously decreasing diagnostic delay for reporting second-line DST. The rapid dissemination of second-line DST results will guide initiation of appropriate treatment, thereby reducing transmission and improving treatment outcome.
Cancer Prevention: Strong Science and Real Medicine
Authors: Scott M. Lippman, Bernard Levin
Journal: Journal of Clinical Oncology (2005)

Many of us working in cancer prevention over the past two decades have begun our primary papers with something resembling the following remarks: ‘‘It is estimated that x cancer will account for y new cancer diagnoses and z deaths in the United States alone this year. These grim statistics persist despite advances in cancer therapy, arguing forcibly for a new approach, such as in cancer prevention, to help in controlling this devastating disease.’’ Alas, this general rationale for cancer prevention is still relevant. In 2004, it is estimated that cancers of the breast, prostate, bladder, colon/rectum, lung/bronchus, and oral cavity/pharynx will account for 856,760 new cancer diag
Therapeutic Strategies Using the Aromatase Inhibitor Letrozole and Tamoxifen in a Breast Cancer Model
Authors: Brian J Long, Danijela Jelovac, Venkatesh Handratta, Apinya Thiantanawat, Nicol MacPherson, Joseph Ragaz, Olga G Goloubeva, Angela M Brodie
Journal: JNCI Journal of the National Cancer Institute (2004)

Background: The antiestrogen tamoxifen has potent activity against estrogen receptor–positive breast cancer, but two nonsteroidal aromatase inhibitors, letrozole and anastrozole, show considerable advantages over tamoxifen with respect to patient survival and tolerability. To determine the optimal way to use letrozole and tamoxifen, we studied their effects on a breast tumor xenograft model, MCF-7Ca, that is responsive to both antiestrogens and aromatase inhibitors. Methods: Female ovariectomized BALB/c athymic nude mice carrying xenograft tumors were treated daily subcutaneously with one of the following first-line therapies for varying durations: no drug (control), tamoxifen (100 μg/day) alone, letrozole (10 μg/day) alone, both drugs at the same time, or alternating 4-week courses of each drug (beginning with a course of tamoxifen or beginning with a course of letrozole). Tumor volumes and weights were estimated using linear mixed-effects models. The time to tumor doubling was calculated, and tumor weights in the treatment groups were compared, with adjustments for multiple comparisons being made with either Tukey's or Dunnett's procedure. Second-line therapies (with tamoxifen, letrozole, or fulvestrant) were initiated when tumors doubled in size under first-line therapies. All statistical tests were two-sided. Results: The times for doubling of tumor volume were as follows: control, 3–4 weeks; tamoxifen alone, 16 weeks; tamoxifen alternating with letrozole, 17–18 weeks; tamoxifen plus letrozole, 18 weeks; letrozole alternating with tamoxifen, 22 weeks; letrozole alone, 34 weeks. First-line treatment with letrozole was superior to treatment with tamoxifen alone or with the two drugs combined (at week 16, both P<.001). Alternating tamoxifen and letrozole and alternating letrozole and tamoxifen were also not as effective as letrozole alone (at week 16, P = .002 and P<.001, respectively). Tumors progressing on tamoxifen remained sensitive to second-line therapy with letrozole compared with those remaining on tamoxifen at the end of treatment (week 28, P<.001), whereas tumors progressing on letrozole were unaffected by second-line treatment with the antiestrogens tamoxifen or fulvestrant. Conclusions: First-line letrozole therapy extends time for tumor progression in this model relative to the other treatment regimens tested. However, further studies are needed to determine the most effective second-line therapy for tumors that progress on letrozole.