tbuckley/cabot-search huggingface dataset:
Management of chronic disease
Authors: C. Teasdale
Journal: BMJ (2002)

Editor—With reference to Wagner's editorial on meeting the needs of chronically ill people, many doctors should remember that patients with chronic diseases are not always socially deprived, are often articulate when their condition is not debilitating their cognitive function, and cannot help being ill.1 Depression is more often brought on by the frustration of dealing with the medical system and attitudes than by the condition.

Could anyone imagine a well person being expected to recover from the effects of accidents or acute illnesses without necessary physiotherapy, treatments, or further follow up appointments? Yet it is expected of people who have a chronic condition, despite the knowledge that such incidents can exacerbate conditions. Is it because doctors are psychologically compartmentalising events into allowable chunks? Condition management is also pointless if patients cannot access the medical services at times when they need them most.

Patients also need to see the same doctor whenever possible, even if it means changing other patients' appointments. It is not an effective use of time and not fair on patients if they have to endure a succession of new faces and temperaments each time they meet with an emergency. Imagine how dreadful it must be for a patient of different cultural values, or from another country, to be facing the prospect of yet another face when English people find the system so daunting themselves.

Affordable treatment choices for chronic conditions are being withheld from people because doctors have habitual prescribing habits, hands-on treatments are still scoffed at, and general practitioners cannot associate and disassociate conditions appropriately for the benefit of their patients. There is also a denial of patients' individuality resulting from a strict adherence to scientifically unsubstantiated protocols. The system is the chronic condition that needs managing.
Abstract 14694: AAV-Mediated Cardiac Transfer of the Desmin cDNA Ameliorates Progression of Cardiomyopathy in Desmin-Deficient Mice
Authors: Ralf Bauer, Markus B Heckmann, Andreas Jungmann, Karl-Heinz Strucksberg, Rolf Schroder, Hugo A Katus, Oliver J Muller
Journal: Circulation (2013)

Introduction: Desmin is a type III intermediate filament which plays a central role in maintaining the structural integrity of cardiac and skeletal muscle cells. Mutations in the desmin coding gene...
Vaccines containing multiple comstimulatory molecules promote the proliferation and activation of human antigen specific memory CD8 T cells.
Authors: Sixun Yang, Doug Grosenbach, Jeffrey Schlom
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

5572 

We have previously shown that recombinant poxvirus vectors containing a triad of T-cell costimulatory molecules (B7-1, ICAM-1, and LFA-3, designated TRICOM) significantly enhanced the levels of CD8+ T-cell responses in preclinical settings. Most recently, we have demonstrated that multiple immunizations with TRICOM-based vaccines can expand antigen specific memory T cells and enhance the functional avidity of memory CD8 T cells in a mouse model. However, the effect of TRICOM-based vaccines on human antigen specific memory CD8 T cells is still unclear. In the present study, human CEA peptide specific CD8 T cells were generated in vitro using T cells from normal donors and CEA peptide pulsed DC as antigen specific cells (APC). Memory CD8 T cells were isolated from in vitro cultures. The proliferation and function of CEA specific memory CD8 T cells following TRICOM signaling were investigated. Our results demonstrated that CEA specific memory CD8 T cells proliferated rigorously as determined by CFSE labeled proliferation assay and tetramer staining following stimulation with CEA peptide pulsed TRICOM-infected APC (APC/TRICOM) as compared with CEA peptide pulsed wild-type control vector-infected APC (APC/WT). Proliferation was dependent on IL-2 and CEA peptide. The CEA tetramer+ CD8 T cells increased 2.35 fold following stimulation with peptide pulsed APC/TRICOM (9.57% of tetramer+ CD8 T cells) as compared with peptide pulsed APC/WT (4.07% of tetramer+ CD8 T cells). IL-2 receptor α (CD25) was upregulated dramatically following APC/TRICOM stimulation suggesting that the enhanced expansion of memory CD8 T cells might be mediated by increased expression of IL-2 receptor on memory T cells. The enhanced proliferation and CD25 expression following TRICOM signaling was completely blocked by adding neutralizing antibodies against ICAM-1, LFA-3 and B7-1. In addition, IFNγ production was significantly increased following APC/TRICOM signaling as judged by intracellular IFNγ staining, especially at lower doses of peptide. Cytolytic activity of CEA specific memory CD8 T cells following 5 day stimulation with APC/TRICOM was also tested. There was no impairment in the functional avidity of TRICOM stimulated memory T cells in that there was no significant difference in their killing capacity and functional avidity between CEA specific memory CTL stimulated with peptide pulsed APC/TRICOM and those stimulated with peptide pulsed APC/WT. No significant difference in T cell apoptosis were observed between APC/TRICOM and APC/WT groups as determined by annexin V staining. The results indicated that TRICOM signaling significantly expanded human CEA specific CD8 T cells without inducing significantly apoptosis of CEA specific memory CD8 T cells.
Israeli health insurer curbs activities of drug representatives
Authors: Judy Siegel-Itzkovich
Journal: BMJ (1999)

Israel's largest public health insurer has decided to restrict the activities of drug company representatives sent to its community clinics and hospitals.

Kupat Holim Clalit, which insures 60% of the population, said that it would bar entry to those representatives who disseminate “false and misleading information” about their products and violate the rules of medical ethics.

The organisation warned that it would file a personal complaint with the police against any representative caught violating these rules. In a letter to the heads of all its districts and hospitals, the head of the health fund's medical branch said …
Kinetic analysis of the fatty acid synthesis pathway in HCT-116 colon cancer cells: role of FAS and ACC1 in maintaining tumor cell viability and proliferation
Authors: Nicole Ginanni, Yanai Zhan, Michael Tota, Margaret Wu, Jennifer Roth, Dennis Ridenour, Peter Strack, Nathan Bays, Eric Bachman, Victoria Richon, Nancy Kohl, Stefan Krauss
Journal: Cancer Research (2007)

4473    De novo  fatty acid synthesis is critical for tumor cell survival, and small molecule inhibitors of this pathway may be useful anti-cancer agents. In this report we sought to evaluate the contributions of two pathway enzymes, acetyl-CoA carboxylase 1 (ACC1) and fatty acid synthase (FAS) on the survival of HCT-116 colon cancer cells. To this end, we performed a kinetic analysis of FAS and ACC1 inhibition using siRNA transfections with two oligonucleotide sequences per target at various concentrations (0, 30 and 60 nM). Cell death (by apoptosis) and viability were assessed and plotted as a function of lipogenesis under the various transfection conditions in order to obtain a specific kinetic profile for knockdown of each enzyme. The resulting curves allowed for a direct comparison of FAS and ACC1 in terms of their significance in maintaining tumor cell viability.  A gradual decrease of lipid biosynthesis by as much as 50% was achieved with siRNA-mediated knockdown of either FAS or ACC1 in HCT-116 cells. Reduced lipid biosynthesis correlated well with the expression of either FAS or ACC1. Furthermore, the changes in apoptosis and viability induced by the siRNA titrations, when plotted against lipogenesis, revealed an identical kinetic profile for both FAS and ACC1. For example, following a reduction in lipid biosynthesis by 25%, about 20% of cells stained positive for apoptosis compared to about 3% in control cells, irrespective of which target was knocked down. These findings strongly support the concept that a decrease in  de novo  lipogenesis, rather than perturbations in pathway intermediates, causes apoptosis in tumor cells when the FAS pathway is inhibited.  It is generally difficult to compare targets in a pathway by using single-point siRNA transfections. One reason for this is that knockdown efficiency, and therefore the resulting functional effects, are likely to vary between different targets. Here, we have applied a kinetic approach using siRNA titrations, which allowed us to directly compare enzymes in the FAS pathway with respect to their role in controlling lipogenesis and tumor cell viability. Our results show that FAS and ACC1 are equally important enzymes for controlling lipogenesis and viability in cultured HCT-116 cancer cells.
Design of CRASH trial
Authors: P. Alderson, I. Roberts
Journal: BMJ (1999)

Editor—Gregson et al re-analyse the meta-analysis in the systematic review of corticosteroids for acute traumatic brain injury published in the BMJ in 1997, of which I was first author.1,2 They present an argument for excluding from the analysis the trial with the most beneficial results,3 thus making the point estimate for the meta-analysis move towards no effect. They use this to condemn the CRASH trial, which is aimed at resolving the uncertainty over the effects of steroids in brain injury.

The systematic review was also published in the Cochrane Library, where it is periodically updated to take account of the results of ongoing searches for studies.4 As well as identifying three more small trials presenting data on deaths, we have found more publications reporting the trial by Faupel et al. As detailed in the original review, the quality score given to this trial meant that we were unclear about how allocation concealment was ensured (not “poor quality” as suggested by Gregson et al). From one publication5 we now have more detail on the procedures used and would classify their use of coded identical vials as adequate quality, or class A. This information will be included in the next update of the review. So there is no reason to exclude this trial on the basis of the quality of allocation concealment as Gregson et al suggest.

Their other argument for ignoring the trial by Faupel et al is that it measured outcomes at discharge, whereas most other trials look at longer term outcomes. We will never know what the outcome of the trial would have been at six months—the apparent benefit of steroids may have decreased, or it could have increased. We judged it better to include the results in the meta-analysis rather than exclude it on the basis of speculation.

Even with their analysis Gregson et al are quite wrong to state that “any possible benefit [of corticosteroids] is eliminated”—the confidence interval still includes a clinically important benefit. We are left with continuing uncertainty over the effect of steroids. This cannot be resolved by re-analysis of existing data—only by the addition of more data from large randomised trials.
Migraine and risk of ischaemic stroke
Authors: A Carolei, C Marini, C Fieschi
Journal: BMJ (1994)

1985 House of Lords ruling in Gillick v DHSS, which still holds good today, may serve to remind doctors of the duty they owe to parents and to their profession.Lord Justice Fraser: "Nobody doubts that in the overwhelming majority of cases the best judges of a child's welfare are his or her parents.Nor do I doubt that any important medical treatment of a child under 16 would normally only be carried out with the parent's approval.That is why it would and should be 'most unusual' for a doctor to advise a child without the knowledge and consent of the parents on contraceptive matters."Lord Justice Scarman: "I accept that great responsibilities will lie on the medical profession.It is however a learned and highly trained profes- sion, regulated by statute and governed by a strict ethical code which is vigorously enforced.Abuse of the power to prescribe contraceptive treatment for girls under the age of 16 would render a doctor liable to severe professional penalty."
Abstract 4342: The RethinQ Trial Echocardiographic Sub Study: Insights from Analysis of TDI Data on Mechanical Dyssynchrony in a Randomized Clinical Trial of Cardiac Resynchronization Therapy in Narrow QRS Patients with Heart Failure
Authors: Richard Grimm, John Beshai, Sherif Nagueh, James Baker, Scott Beau, Steven Greenberg, Luis Pires, Patrick Tchou
Journal: Circulation (2008)

Tissue Doppler Imaging (TDI) of myocardial velocities is the method of choice to characterize mechanical dyssynchrony (MD) in the failing heart. TDI identified candidates for the RethinQ trial, a prospective, randomized, multicenter, double-blind, parallel-controlled trial evaluating the efficacy of Resynchronization Therapy (CRT) in pts with EF &lt;35%, NHYA class III, QRS &lt;130 ms and MD by TDI. Peak MVO 2 at 6 months was the primary endpoint. The purpose of this study was to determine whether: degree of MD by TDI and opposing wall delay (OPWD) correlated with outcome; resynchronization by TDI parameters of MD was achieved by CRT; and if other TDI parameters of MD were predictive of outcome. Methods: A retrospective analysis of prospectively acquired echo data. Pts underwent an echo exam at baseline and 6 months which included color TDI enabling determination of the OPWD ≥65 ms required for enrollment into the trial. Other recognized parameters of MD such as the pre-ejection period (PEP) and 12 segment standard deviation of time-to-peak myocardial velocity were collected but not part of the selection criteria used to randomize pts to CRT. For the purpose of this analysis responders (R) were defined by improved MVO 2 and reduction in LVESV&gt; 15%. All echo data was adjudicated by a Core Lab. Results: Degree of dyssynchrony pre implant (OPWD &gt; 65, &gt; 80, &gt; 100ms) did not impact response to CRT. Both R and Non responders (NR) exhibited a decrease in OPWD at 6 months though R had a greater median change than NR -33(−29+42) ms vs 0(−3+45) ms, p=0.01. When pts exhibited OPWD ≥65ms, 12 segment standard deviation ≥34ms and PEP &gt; 100ms there was a trend toward being able to identify R to CRT pre implant. 18/65 (28%) pts receiving CRT and meeting all 3 MD criteria were categorized as R vs. 6/47 (13%) not receiving CRT, p=0.052. Conclusions: Analysis of the echo TDI data revealed that degree of MD did not impact outcome, improvement of dyssynchrony was achieved with CRT and a combination of OPWD≥65ms, 12 segment standard deviation ≥34ms and pre ejection period &gt; 100ms showed promise in predicting improvement in pts with narrow QRS, low EF and MD.
Abstract 12199: What is the Optimal Prognostic Method for Scoring Coronary Artery Disease on a CT Angiogram? Results from the Multinational CONFIRM Registry (Coronary CT Angiography Evaluation For Clinical Outcomes: An International Multicenter Registry)
Authors: Martin Hadamitzky, Stephan Achenbach, Mouaz Al-Mallah, Daniel S Berman, Matthew J Budoff, Tracy Q Callister, Hyuk-Jae Chang, Victor Cheng, Benjamin J Chow, Augustin Delago, Ronald P Karlsberg, Philipp Kaufmann, Fay Y Lin, James K Min, Khurram Nasir, Leslee J Shaw, Jorg Hausleiter
Journal: Circulation (2010)

Background: Coronary CT angiography (CCTA) is an emerging modality for assessing coronary artery disease (CAD). Besides the detection of obstructive disease, it can detect both nonobstructive calci...
Aldo-keto reductase 1 b10 protects colorectal cancer cells from 4-hydroxy-2-nonenal-induced apoptosis
Authors: Chun Wang, Ruilan Yan, Xuyu Zu, Duan-Fang Liao, Deliang Cao
Journal: Cancer Research (2008)

AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA

2697 

Aldo-keto reductase 1 B10 (AKR1B10, also designated aldose reductase-like-1, ARL-1), a member of aldo-keto reductase (AKR) superfamily, is overexpressed in human liver, lung, and breast cancer, but its pathophysiological function in cancer development and progression remains unclear. In the present study, we investigated the protective role of AKR1B10 against 4-hydroxy-2-nonenal (HNE), a highly toxic product of lipid peroxidation. HCT-8 cells derived from colon adenocarcinoma exhibit abundant AKR1B10 transcripts and were thus used for generation of a stable cell model with AKR1B10 silencing, in which a small interfering RNA (siRNA) targeting 3’-untranslational region of AKR1B10 was introduced using pSUPEROR® vector (Oligoengine, Seattle, Washington) mediated shRNA system. Three clones with different extent of AKR1B10 knockdown were isolated and used for HNE response studies. Two empty vector clones were isolated for a control. Our resulting data demonstrate that AKR1B10 knockdown triggered a p53-mediated apoptosis of HCT-8 cells when exposed to HNE at various concentrations. Phosphorylated H2AX was stained in discrete foci in nuclei of HCT-8 cells with AKR1B10 knockdown; p53 levels were considerably increased; and caspase-3 and PARP were activated in these cells. These data indicate that HNE induced DNA damage and in turn, trigger p53-mediated apoptosis of AKR1B10 silenced HCT-8 cells. Further studies exhibited that apoptosis appeared to occur via mitochondrion-mediated pathway; in these cells increased cytochrome C release was detected. Taken together, our data demonstrate that AKR1B10 protects HCT-8 cells from HNE-induced DNA damage and subsequent p53-mediated apoptosis. To further understand the biochemical basis of this protection, HNE metabolites in these cells are being analyzed by high-performance liquid chromatography (HPLC).
Abstract 2115: Relationship Between Stature and the Prevalence of Atrial Fibrillation and Cardiovascular Mortality
Authors: Swee Y Tan, Jonathan Myers, Victor F Froelicher
Journal: Circulation (2006)

Background: A recent study ( JACC Apr 2006 ; 47 : 1683 –1688 ) suggested that atrial fibrillation was more prevalent in patients of tall stature (AF) . However, the impact that this association has on survival is unknown. Aims: To validate the previous findings regarding height and to investigate how height and atrial fibrillation effect survival. Methods: Computerized 12 lead resting ECGs on 45,855 consecutive male veterans obtained by physician discretion at the Palo Alto Veterans Affairs Medical Center from 1987 to 2000 were analyzed. After excluding inpatients, patients with WPW, paced rhythms and inpatients, 29,587 patients remained. After a mean follow up of 7.5 ± 3.8years, there were 2,616 cardiovascular (CV) deaths (8.8%). Age and heart rate adjusted proportional hazard analyses were performed. Tall patients were considered those in the 75th percentile (71 inches and above). Results: There were 2468 patients with atrial fibrillation. Mean height of people with AF was 69.4 ± 3.6 inches while those without AF was 68.6 ± 3.7 (p&lt;0.001). Prevalence of AF in tall people was 3.2% whilst it was 2.6 % in shorter individuals (Chi-Square 11.4 p&lt;0.001). Being of tall stature and having AF were associated both univariately and multivariately with cardiovascular mortality. Kaplan-Meier curves show significant differences between patients who were tall with AF and who were short with AF. Conclusion: This study confirms the recent observation that tall individuals have a higher prevalence of AF. Tall stature protects from cardiovascular mortality even in patients with AF.
Revel in electronic and paper media
Authors: T. Delamothe
Journal: BMJ (2000)

Some BMJ readers are proud of not using the world wide web. Others are scornful of paper media, predicting that one day everything will be purely electronic. Both are wrong, and we urge BMJ readers and authors to exploit to the full both paper and electronic media.

The BMJ has two audiences that overlap only a little. Each week we send out about 115 000 paper journals, mostly to people in Britain. Yet in any one week only about 5-10% of these people access bmj.com. At the same time we have around 100 000 weekly visitors to bmj.com. Most …
Abstract 2584: Darusentan Significantly Reduces Systolic Blood Pressure in Patients with Resistant Hypertension on 4 or More Antihypertensive Drugs
Authors: Michael Weber, Henry Black, Stuart Linas, Marshelle Warren, Rebecca Light, Brian L Wiens, George Bakris
Journal: Circulation (2006)

Purpose: Patients with resistant hypertension (RHTN) as defined by JNC 7 guidelines do not achieve recommended systolic blood pressure (SBP) goals despite treatment with multidrug antihypertensive ...
Abstract 16093: Effects of Aliskiren and Amlodipine Combination Treatment on Endothelial Nitric Oxide and Peroxynitrite Release in Hypertensive Rats
Authors: R P Mason, Robert F Jacob, Roman Kaliszan, J. J Corbalan, Tadeusz Malinski
Journal: Circulation (2011)

Background: Endothelial cell (EC) dysfunction is causally related to atherosclerosis and hypertension. Aliskiren, a direct renin inhibitor, and amlodipine, a calcium channel blocker, have each been...
Xenograft Models of Multiple Myeloma Reveal That PU.1 Serves As a Tumor Suppressor for Multiple Myeloma
Authors: Nao Nishimura, Shinya Endo, Niina Ueno, Shikiko Ueno, Hiromichi Yuki, Hiroyuki Hata, Hiroaki Mitsuya, Yutaka Okuno
Journal: Blood (2014)
Low expression of Bax in non-small cell lung cancer: Predictor of poor disease-free survival in adenocarcinoma patients with surgical resection
Authors: Ho-Yeong Lim, Jin-Hyuk Choi, Seog Yun Kang, Youn Mu Jung, Hugh Chul Kim, Young Taek Oh, Ho Choi, Seong Chul Hwang, Kwang Joo Park, Jae Ho Han
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

4538 

Bax protein, which belongs to a family of bcl-2, is known to promote apoptosis, and decreased expression of Bax has been associated with poor progosis in several malignancies. We investigated the expression of Bax and its association with clinicopatholgic characteristics including disease-free survival (DFS) and overall survival (OS) in 209 non-small cell lung cancer (NSCLC) patients (pts) who underwent surgical resection (stage I: 97, II: 46, IIIA: 45, IIIB: 17, IV: 4) using immunohistochemistry. Ninety-one pts (44%) received adjuvant treatment (chemotherapy: 9, radiotherapy: 24, both: 58). Low expression of Bax (no or weak staining in intensity) was observed in 159 pts (76%), which was significantly associated with male gender (p 4 cm) (p=0.017). In conclusion, low expession of Bax was significantly associated with poor DFS in NSCLC pts with adenocarcioma or adenosquamous carcinoma histology.
Gastroenterological Society of Australia
Authors: D J Saint John, F T McDermott
Journal: Gut (1969)

In most normal 6 gug/kg/ hr) were infused intravenously for 75 minutes on separate days.In other studies, a 750ml test meal was given 45 minutes after the start of the pentapeptide infusion and aspirated 30 minutes later.Acid output in response to 750 ml was greater than that in response to 375 ml (p < 001) but not significantly different from that in response to 1,500 ml (p > 0.1).Acid output (mean + SEM in m-equiv/30 minutes) in response 950 on July 17, 2023 by guest.