tbuckley/cabot-search huggingface dataset:
Abstract 2209: Contribution of <i>FKBP5</i> genetic variation to gemcitabine treatment and survival in pancreatic cancer.
Authors: Katarzyna A. Ellsworth, Bruce W. Eckloff, Liang Li, Irene Moon, Brooke L. Fridley, Greg D. Jenkins, Erin Carlson, Abra Brisbin, Ryan Abo, William Bamlet, Gloria Petersen, Eric D. Wieben, Liewei Wang
Journal: Cancer Research (2013)

Abstract The FKBP5 gene encodes the FKBP51 immunophilin, a negative regulator of AKT. Variability in level of FKBP5 expression is a major factor contributing to variation in response to several classes of chemotherapeutic agents including gemcitabine, first line treatment for pancreatic cancer. Genetic variation of FKBP5 could influence its expression, function, and, ultimately, treatment response of pancreatic cancer. We set out to comprehensively study the role of genetic variation in FKBP5 identified by Next Generation DNA resequencing in response to gemcitabine treatment of pancreatic cancer by utilizing both tumor and germline DNA samples from 43 pancreatic cancer patients, including 19 paired tumor-normal samples. Genotype-phenotype association studies with overall survival (in tumor only) as well as with FKBP5 gene expression were performed using the same samples in which Next Generation DNA resequencing had been performed, followed by functional genomic studies of top selected single nucleotide polymorphisms (SNPs). In-depth resequencing identified 404 FKBP5 SNPs in both normal and tumor DNA patient samples. SNPs with the smallest p-values for association with FKBP5 survival or expression were subjected to functional genomic studies. Electromobility shift assay (EMSA) showed that the rs73748206 “T” allele altered DNA-protein binding patterns, consistent with a significantly increased reporter gene activity. The effect of rs73748206 was also confirmed by mRNA expression studies using lymphoblastoid cell lines (LCL) derived from the same patients from whom DNA used for resequencing had been obtained. This comprehensive FKBP5 resequencing study provides insight into the role of inheritance in variation in response to gemcitabine therapy of pancreatic cancer. Citation Format: Katarzyna A. Ellsworth, Bruce W. Eckloff, Liang Li, Irene Moon, Brooke L. Fridley, Greg D. Jenkins, Erin Carlson, Abra Brisbin, Ryan Abo, William Bamlet, Gloria Petersen, Eric D. Wieben, Liewei Wang. Contribution of FKBP5 genetic variation to gemcitabine treatment and survival in pancreatic cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2209. doi:10.1158/1538-7445.AM2013-2209
Preoperative Banditry: Surgeons React
Authors: Robert H. Bradley
Journal: JAMA (1990)

<h3>To the Editor.—</h3> How can our profession apologize sufficiently to the trusting public that believes in the humanity of physicians for the unconscionable and ruthless venality exhibited by the surgeon described by Ms Richmond?<sup>1</sup>Seeking payment prior to surgery is rare in the medical community, but it does happen, and the word gets around to tar us all. A torrent of adjectives comes to mind: outrageous, disgusting, nauseating, rapacious, greedy, grasping, unthinkable banditry. Money up front from an acutely ill patient is extortion, and must be condemned as such. Surely organized medicine can act to let the public know that we do not sanction piracy.
Adequacy of Dialysis
Authors: Samuel Vaisrub
Journal: JAMA (1975)

Cost/benefit considerations often enter into the making of many therapeutic decisions. Sometimes when the alternative to benefit is certain death, the decision is simplified. The public or private sector of our humane society will assist the threatened individual. Life must be preserved at all costs. But, even in desperate situations, cost becomes an important decisional factor, if a choice exists between two or more life-sustaining measures. Decisions then have to be made on the basis of comparative cost, and this is no simple matter, as is well illustrated in the treatment of renal failure. Hemodialysis and renal transplantation often compete for priority of choice in advanced renal failure. Each of these two treatment modalities carries its own complex of costs and benefits. The benefits of renal transplantation are obvious. Patients with successfully grafted kidneys do not depend on a machine—a psychological bonus of no small moment. They have greater freedom
1179 INTERFERON LAMBDA GENOTYPE AND LOW SERUM LDL CHOLESTEROL LEVELS IN PATIENTS WITH CHRONIC HEPATITIS C INFECTION
Authors: J.H. Li, X.Q. Lao, H. Tillmann, J. Rowell, K. Patel, A.J. Thompson, S. Suchindran, A.J. Muir, J.R. Guyton, S.D. Gardner, J.G. McHutchison, J. McCarthy
Journal: Journal of Hepatology (2010)
On Awakening Paralyzed During Surgery-Reply
Authors: Richard S. Blacher
Journal: JAMA (1976)

In Reply.—  It is gratifying to have one's observations confirmed by the observations of colleagues. In my article I referred to the literature concerning awareness during surgery, and I attempted to demonstrate that in some instances this experience can have a profound and even lasting effect. Drs Silbergleit, Messer, and Archer, as well as Ms Michael, support this with clinical data. Dr Archer answers some of Dr Larson's objections quite well. I would add that I do not suggest that the dose of anesthesia was inadequate nor that the anesthesiologists were negligent. It goes without saying that the first consideration must be the preservation of the patient's life, and for this reason, as Dr Jobes points out, light levels are often necessary. Psychic distress is clearly a better choice than death, and I would prefer to try to patch up the psyche of a living patient than have him die
Incidence of HIV Infection in a New York City Methadone Maintenance Treatment Program
Authors: Maureen F. Orr
Journal: JAMA (1996)

<h3>To the Editor.</h3> —To estimate the incidence of human immunodeficiency virus (HIV) infection (seroconversions), a retrospective study of records from a voluntary HIV counseling and testing program at a New York City methadone maintenance treatment program (MMTP) was initiated. The study included records of patients who had 2 or more HIV tests and were HIV-negative on the initial test. A seroconverter was defined as a person with an initial HIV-negative test followed by an HIV-positive test. The seroconversion rate (incidence density of HIV infections) was calculated by dividing the number of seroconverters by the total number of personyears of follow-up. The follow-up time for nonseroconverters included the time between the initial test and the last test. For seroconverters, follow-up time was calculated as the midpoint between the last HIV-negative test and the first HIV-positive test. From July 1990 to April 1994, a total of 1833 voluntary HIV tests were conducted
<i>BRCA1</i>— Lots of Mutations, Lots of Dilemmas
Authors: Francis S. Collins
Journal: New England Journal of Medicine (1996)

Breast cancer is the most common cancer among women in the Western world, with a cumulative lifetime risk of 1 in 8.1 The two strongest risk factors are age and a family history of breast cancer. Five years ago, a region on chromosome 17 was shown by linkage analysis to have a substantial role in early-onset familial breast and ovarian cancer.2 An intense gene-hunting effort of the “positional cloning” type3 culminated in the identification of the BRCA1 gene in the fall of 1994.4,5 These results will require that all physicians who care for patients understand the molecular genetics of . . .
A Functional Variant of Elafin With Improved Anti-inflammatory Activity for Pulmonary Inflammation
Authors: Donna M Small, Marie-Louise Zani, Derek J Quinn, Sandrine Dallet-Choisy, Arlene MA Glasgow, Cecilia O'Kane, Danny F McAuley, Paul McNally, Sinéad Weldon, Thierry Moreau, Clifford C Taggart
Journal: Molecular Therapy (2014)

Elafin is a serine protease inhibitor produced by epithelial and immune cells with anti-inflammatory properties. Research has shown that dysregulated protease activity may elicit proteolytic cleavage of elafin, thereby impairing the innate immune function of the protein. The aim of this study was to generate variants of elafin (GG- and QQ-elafin) that exhibit increased protease resistance while retaining the biological properties of wild-type (WT) elafin. Similar to WT-elafin, GG- and QQ-elafin variants retained antiprotease activity and susceptibility to transglutaminase-mediated fibronectin cross-linking. However, in contrast to WT-elafin, GG- and QQ-elafin displayed significantly enhanced resistance to degradation when incubated with bronchoalveolar lavage fluid from patients with cystic fibrosis. Intriguingly, both variants, particularly GG-elafin, demonstrated improved lipopolysaccharide (LPS) neutralization properties in vitro. In addition, GG-elafin showed improved anti-inflammatory activity in a mouse model of LPS-induced acute lung inflammation. Inflammatory cell infiltration into the lung was reduced in lungs of mice treated with GG-elafin, predominantly neutrophilic infiltration. A reduction in MCP-1 levels in GG-elafin treated mice compared to the LPS alone treatment group was also demonstrated. GG-elafin showed increased functionality when compared to WT-elafin and may be of future therapeutic relevance in the treatment of lung diseases characterized by a protease burden.
Comparison of carbon dioxide (CO2) to air insufflation in colonoscopy
Authors: R. Ramaraj, A. Sugumaran, H. Khan, T. Mathialahan, P. George
Journal: Gut (2011)

<h3>Introduction</h3> It is well known that CO2 insufflation reduces pain during and after colonoscopy. However air insufflation is more popular probably due to limited randomised studies.1 This study compares the effects of air and CO2 insufflation on pain during and after colonoscopy. <h3>Methods</h3> The study was conducted over a 3-month period and 126 patients were randomly assigned into CO2 or air insufflation groups. Discomfort scores during and after colonoscopy was recorded using the modified gloucester discomfort score and factors influencing outcome such as sex, endoscopist grade, previous surgery and sedation were also considered. <h3>Results</h3> Of 126 in the study, air was used in 36 and CO2 in 90. The caecal intubation rate in CO2 was 95% versus 91% in the air group. Patients in the CO2 group had lower pain scores during the procedure compared to air. During the procedure, 51.6% CO2 versus 36.11% (Air) had no discomfort at all (score 1). Patients who had a score of 2, 3 were 46% Air versus 40% CO2. There was a higher pain score (4, 5) noted at 7% versus 2.7% (Air) noted mainly in females (83.3%). Postprocedure discomfort scores were almost equal noted to be 1.19 Air versus 1.06 at 1 h and 1.08 versus 1.00 CO2 at 2 h. A number of factors were taken into consideration to see whether this influenced discomfort scores. (1) <i>Sex</i>: 57 males and 69 females were in the study. Females had higher pain scores 31.34% versus 15.52% (males). However this was not statistically significant using the Mann–Whitney test. (2) <i>Sedation</i>: Average sedation used, midazolam (M) 1.93 versus 0.67 mg CO2, Pethidine 9 versus 14 mg CO2, fentanyl 34 versus 17 mg CO2. Average top up sedation used was 0.02 versus 0.05 mg CO2 of M, Pethidine 0.69 versus 0.5 mg CO2 and fentanyl 2.5 mg top up for CO2 group versus no top up. (3) <i>Previous surgery</i>: Data for only 74 patients was available. Those patients who have had no previous surgery (n=50) appear to have lower discomfort levels, however data points for pelvic surgery were too few to come to a conclusion. (4) <i>Endoscopist</i>: Discomfort scores were higher in trainees (n=34) using CO2 than consultants (n=56). Using Mann–Whitney test this was statistically significant with a CI of 95.1%. There was no difference in scores in air group. In the consultant group, using CO2 lowered patient discomfort compared to air (p=0.06) that was statistically significant. <h3>Conclusion</h3> Though CO2 insufflation is said to be effective in reducing postprocedural discomfort there was not much difference in both groups however pain was reduced during procedure in the C02 group. Caecal intubation rate was slightly higher in the CO2 group and endoscopist grade, sex and previous surgery influenced outcome.
Identification of Early T1b Lung Adenocarcinoma Based on Thin-Section Computed Tomography Findings
Authors: Keiju Aokage, Junji Yoshida, Genichiro Ishii, Yuki Matsumura, Tomohiro Haruki, Tomoyuki Hishida, Kanji Nagai
Journal: Journal of Thoracic Oncology (2013)
Rapidly Progressing Leg Ulcer With Fever in a Woman With Chronic Diarrhea
Authors: Hai Long, Yuwen Su, Qianjin Lu
Journal: JAMA (2014)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
The evidence for beta blockers in heart failure
Authors: J. G. Cleland, J McGowan, A. Clark, N. Freemantle
Journal: BMJ (1999)

Heart failure is a common, malignant condition for which hospital admissions are rising rapidly.1–3 Despite the evidence that angiotensin converting enzyme inhibitors improve the morbidity and mortality of heart failure secondary to left ventricular systolic dysfunction, the prognosis of heart failure in the community has improved little over the past 30 years.4 This may reflect a reluctance to prescribe angiotensin converting enzyme inhibitors.4 Now, however, evidence has accumulated to show that β blockers, when used in addition to angiotensin converting enzyme inhibitors, also reduce mortality in heart failure. Will this be another lost opportunity?

The CIBIS-II study,5 comparing bisoprolol with placebo, recently reported a highly significant reduction in all cause mortality. When these data and those from other smaller trials6–8 identified from searches of Medline and Embase and recent meetings9 are added to those reported in previous meta-analyses10 there are now 25 trials that have randomised patients with heart failure to β blocker or control, comprising 6511 patients and 810 deaths. Overall β blockers reduced the odds of death by 36% (95% confidence interval 25% to 45%) (fig 1). There is no evidence of heterogeneity between …
128 BIPHASIC YB-1 ACTIVATION BY DIFFERENT MECHANISMS MEDIATES HEPATIC MRP2 SUPPRESSION AND MMP-2 INDUCTION BY PROINFLAMMATORY SIGNALS
Authors: I.V. Martin, P.R. Mertens, B. Frye, S. Strauch, T. Rauen, C. Trautwein, A. Geier
Journal: Journal of Hepatology (2008)
Health secretary announces plan to overhaul "disjointed care" delivered by GPs
Authors: M. Limb
Journal: BMJ (2013)

England’s health secretary, Jeremy Hunt, has announced plans to overhaul primary care to improve its quality, provoking calls for clarity among doctors’ leaders.

Hunt said that the move was a “more urgent” priority than improving standards in hospitals. His measures include recruiting more GPs, making them more “accountable” for out of hours care, and creating a new chief inspector of general practice within the Care Quality Commission.

Hunt said that there might be changes to the GP contract introduced by Labour in 2004, which he said had “fatally undermined the personal link between GPs and their patients.”

He said, “Reclaiming the ideal of family doctoring in the 21st century means making sure clinicians are accountable for people who are unwell—whether inside or outside hospital. It means responsibility for more proactive care.”

The NHS Alliance, which represents primary care professionals and organisations, said that Hunt’s plans to make GPs accountable were unclear.

The Royal College of General Practitioners warned …
PMO-166 Early experience with telaprevir for patients with advanced fibrosis or cirrhosis
Authors: M E Cunningham, J Schulz, L Payaniandy, Y Kallis, P Kennedy, P Kooner, R Marley, G R Foster
Journal: Gut (2012)

<h3>Introduction</h3> The direct-acting HCV protease inhibitor telaprevir has recently been licensed for treatment of chronic genotype 1 HCV infection, and promises significant improvements in sustained virological response for these patients. However the patients who may benefit most from novel HCV therapies, namely those with advanced fibrosis or cirrhosis who have previously failed to respond to pegylated interferon (pegIFN) and ribavirin treatment, are relatively poorly represented in the telaprevir clinical trials. Efficacy, safety and tolerability were assessed in patients with genotype 1 HCV and advanced fibrosis/cirrhosis who have received telaprevir-containing treatment at the Royal London Hospital. <h3>Methods</h3> Laboratory results and case notes were reviewed for all patients treated with pegIFN, ribavirin and telaprevir at the Royal London Hospital between September 2011 and January 2012. <h3>Results</h3> Eight patients with genotype 1 HCV had commenced telaprevir-containing treatment. All had advanced fibrosis/cirrhosis (median Ishak score 5, range 4–6). One was treatment-naïve, three had previously failed to respond to pegIFN/ribavirin and four had relapsed after therapy. All patients had completed at least 4 weeks of telaprevir-containing therapy. With one exception, all patients achieved undetectable HCV RNA at week 4 of treatment; the patient who did not had a viral load of 168 IU/ml at week 4 and undetectable HCV RNA at week 8. One patient had completed 12 weeks of therapy, with undetectable HCV RNA. The most common side effects were fatigue (8/8), pruritis (4/8), rash (3/8), anal pain (3/8), depression (3/8), nausea (3/8), gastrointestinal disturbance (2/8) and oral candidiasis (2/8). Most side effects were successfully managed, although telaprevir was stopped in two patients at week 8 due to worsening rash and one patient withdrew from all therapy at week 4 due to tolerability. The most common laboratory abnormality was an early, transient rise in bilirubin (3/8). Significant anaemia (Hb). <h3>Conclusion</h3> Telaprevir in combination with pegIFN and ribavirin appears efficacious in patients with advanced fibrosis or cirrhosis, who have previously failed treatment with pegIFN and ribavirin alone. However, the incidence of significant side effects in this subgroup of patients is high and necessitates frequent follow-up with medical support. Side effects, particularly rash, may limit duration of telaprevir treatment. Whether this impacts on sustained virological response remains to be seen. <h3>Competing interests</h3> M Cunningham: None declared, J Schulz: None declared, L Payaniandy: None declared, Y Kallis: None declared, P Kennedy: None declared, P Kooner: None declared, R Marley: None declared, G Foster grant/research Support from: Roche, Janssen, Tibotec, Novartis, Consultant for: Abbott, BI, BMS, Chughai, Janssen, Merck, Novartis, Roche, Tibotec.
Determining the evolutionary potential of a gene
Authors: B. G. Hall, H. S. Malik
Journal: Molecular Biology and Evolution (1998)

In addition to information for current functions, the sequence of a gene includes potential information for the evolution of new functions. The wild-type ebgA (evolved beta-galactosidase) gene of Escherichia coli encodes a virtually inactive beta-galactosidase, but that gene has the potential to evolve sufficient activity to replace the lacZ gene for growth on the beta-galactoside sugars lactose and lactulose. Experimental evidence, which has suggested that the evolutionary potential of Ebg enzyme is limited o two specific amino acid replacements, is limited to examining the consequences of single base-substitutions. Thirteen beta-galactosidases homologous with the Ebg beta-galactosidase are widely dispersed, being found in gram-negative and gram-positive eubacteria and in a eukaryote. A comparison of Ebg beta-galactosidase with those 13 beta-galactosidases shows that Ebg is part of an ancient clade that diverged from the paralogous lacZ beta-galactosidase over 2 billion years ago. Ebg differs from other members of its clade at only 2 of the 15 active-site residues, and the two mutations required for full Ebg beta-galactosidase activity bring Ebg into conformity with the other members of its clade. We conclude that either these are the only acceptable amino acids at those positions, or all of the single-base-substitution replacements that must arise as intermediates on the way to other acceptable amino acids are so deleterious that they constitute a deep selective valley that has not been traversed in over 2 billion years. The evolutionary potential of Ebg is thus limited to those two replacements.
Mycobacterium tuberculosis enhances human immunodeficiency virus-1 replication by transcriptional activation at the long terminal repeat.
Authors: Y Zhang, K Nakata, M Weiden, W N Rom
Journal: Journal of Clinical Investigation (1995)

Tuberculosis has emerged as an epidemic fueled by the large number of individuals infected with the human immunodeficiency virus, especially those who are injecting drug users. We found a striking increase from 4- to 208-fold in p24 levels in bronchoalveolar lavage fluid from involved sites of Mycobacterium tuberculosis infection vs uninvolved sites in three HIV+ patients. We used an in vitro cell culture model to determine if tuberculosis could activate replication of HIV-1. Mononuclear phagocyte cell lines U937 and THP-1 infected with HIV-1JR-CSF, in vitro and stimulated with live M. tuberculosis H37Ra, had a threefold increase in p24 in culture supernatants. Using the HIV-1 long terminal repeat with a chloramphenicol acetyltransferase (CAT) reporter construct, live M. tuberculosis increased transcription 20-fold in THP-1 cells, and cell wall components stimulated CAT expression to a lesser extent. The nuclear factor-kappa B enhancer element was responsible for the majority of the increased CAT activity although two upstream nuclear factor-IL6 sites may also contribute to enhanced transcription. Antibodies to TNF-alpha and IL-1 inhibited the increase in CAT activity of the HIV-1 long terminal repeat by M. tuberculosis from 21-fold to 8-fold. Stimulation of HIV-1 replication by M. tuberculosis may exacerbate dysfunction of the host immune response in dually infected individuals.
Prolonged exposure to inhaled nitric oxide does not affect haemostasis in piglets
Authors: Johanna Albert, Piotr Harbut, Stanisław Zieliński, Stanisław Ryniak, Caroline Gillis-Haegerstrand, Robert Lindwall, Leszek Solski, Jon O. Lundberg, Jan Svensson, Waldemar Goździk
Journal: Intensive Care Medicine (2007)