tbuckley/cabot-search huggingface dataset:
Performance characteristics of magnetic resonance cholangiography in the staging of malignant hilar strictures
Authors: S H Zidi
Journal: Gut (2000)

<h3>BACKGROUND</h3> Magnetic resonance cholangiography (MRC) is currently under investigation for non-invasive biliary tract imaging. <h3>AIM</h3> To compare MRC with endoscopic retrograde cholangiography (ERC) for pretreatment evaluation of malignant hilar obstruction. <h3>METHODS</h3> Twenty patients (11 men, nine women; median age 74 years) referred for endoscopic palliation of a hilar obstruction were included. The cause of the hilar obstruction was a cholangiocarcinoma in 15 patients and a hilar compression in five (one hepatocarcinoma, one metastatic breast cancer, one metastatic leiomyoblastoma, two metastatic colon cancers). MRC (T2 turbo spin echo sequences; Siemens Magnetomvision 1.5 T) was performed within 12 hours before ERC, which is considered to be the ideal imaging technique. Tumour location, extension, and type according to Bismuth9s classification were determined by the radiologist and endoscopist. <h3>RESULTS</h3> MRC was of diagnostic quality in all but two patients (90%). At ERC, four patients (20%) had type I, seven (35%) had type II, seven (35%) had type III, and two (10%) had type IV strictures. MRC correctly classified 14/18 (78%) patients and underestimated tumour extension in four (22%). Successful endoscopic biliary drainage was achieved in 11/17 attempted stentings (65%), one of which was a combined procedure (endoscopic + percutaneous). One patient had a percutaneous external drain, one had a surgical bypass, and in a third a curative resection was attempted. Effective drainage was not achieved in six patients (30%). If management options had been based only on MRC, treatment choices would have been modified in a more appropriate way in 5/18 (28%) patients with satisfactory MRC. <h3>CONCLUSION</h3> MRC should be considered for planning treatment of malignant hilar strictures. Accurate depiction of high grade strictures for which endoscopic drainage is not the option of choice can preclude unnecessary invasive imaging.
The global burden of occupationally related low back pain: estimates from the Global Burden of Disease 2010 study
Authors: T Driscoll, G Jacklyn, J Orchard, E Passmore, T Vos, G Freedman, S Lim, L Punnett
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Objectives</h3> The study was part of the Global Burden of Disease 2010 study and aimed to quantify the burden arising from low back pain (LBP) due to occupational exposure to ergonomic risk factors. <h3>Methods</h3> Exposure prevalence was based on occupation distribution; estimates of relative risk came from a meta-analysis of relevant published literature. The work-related burden was estimated as disability-adjusted life years (DALYs). Estimates were made for each of 21 world regions and 187 countries, separately for 1990 and 2010 using consistent methods. <h3>Results</h3> Worldwide, LBP arising from ergonomic exposures at work was estimated to cause 21.7 million DALYs in 2010. The overall population attributable fraction was 26%, varying considerably with age, sex and region. 62% of LBP DALYs were in males—the largest numbers were in persons aged 35–55 years. The highest relative risk (3.7) was in the agricultural sector. The largest number of DALYs occurred in East Asia and South Asia, but on a per capita basis the biggest burden was in Oceania. There was a 22% increase in overall LBP DALYs arising from occupational exposures between 1990 and 2010 due to population growth; rates dropped by 14% over the same period. <h3>Conclusions</h3> LBP arising from ergonomic exposures at work is an important cause of disability. There is a need for improved information on exposure distributions and relative risks, particularly in developing countries.
Biochemical Outcome Following External Beam Radiation Therapy With or Without Androgen Suppression Therapy for Clinically Localized Prostate Cancer
Authors: A V D'Amico, D Schultz, M Loffredo, R Dugal, M Hurwitz, I Kaplan, C J Beard, A A Renshaw, P W Kantoff
Journal: JAMA (2000)

Combined treatment using radiation therapy (RT) and androgen suppression therapy (AST) is used to treat men with clinically localized adenocarcinoma of the prostate, but outcome using this combined therapy compared with RT alone is not known.To determine the relative efficacy of RT plus AST vs RT alone among men with clinically localized prostate cancer.Retrospective cohort study of 1586 men with prostate cancer who were treated between January 1989 and August 1999 using 3-dimensional conformal RT with (n = 276) or without (n = 1310) 6 months of AST.Relative risk (RR) of prostate-specific antigen (PSA) failure (defined according to the American Society for Therapeutic Radiology and Oncology consensus statement), by treatment and high-, intermediate-, or low-risk group based on serum PSA level, biopsy Gleason score, and 1992 American Joint Commission on Cancer clinical tumor category.Estimates of 5-year PSA outcome after RT with or without AST were not statistically different among low-risk patients (P =.09), whereas intermediate- and high-risk patients treated with RT plus AST had significantly better outcomes than those treated with RT alone (P<.001 and =.009, respectively). The RR of PSA failure in low-risk patients treated with RT plus AST was 0.5 (95% confidence interval [CI], 0.3-1.1) compared with patients treated with RT alone. The RRs of PSA failure in intermediate-risk and high-risk patients treated with RT plus AST compared with RT alone were 0.2 (95% CI, 0. 1-0.3) and 0.4 (95% CI, 0.2-0.8), respectively.Our data suggest a significant benefit in 5-year PSA outcomes for men with clinically localized prostate cancer in intermediate- and high-risk groups treated with RT plus AST vs those treated with RT alone. Results from prospective randomized trials currently under way are needed to validate these findings. JAMA. 2000;284:1280-1283
Spread of Excitation from the Sinus Node
Authors: TOYOMI SANO, SHUNICHI YAMAGISHI
Journal: Circulation Research (1965)

Microelectrodes were employed to determine the mode of propagation of excitation from the sinus node in the rabbit heart. The excitation starts from the sinus node radially, at first, but then proceeds to the crista terminalis, often obliquely. This is because some special tissue having a slow conduction velocity lies behind the sinus node, and also because there is a zone of relatively faster conduction at the basal wall of the superior vena cava. Once the excitation wave enters the crista terminalis, it travels rapidly in two opposite directions through two branches of the ring-like structure which is formed by the crista terminalis and its extension. The excitation wave traveling through the branch encircling the inferior vena cava reached the atrioventricular node earlier in most instances. In the caval region inside the ring-like structure there is a zone of relatively faster conduction. The conduction to the atrioventricular node through this route is latent in the normal state, because conduction through the ring-like structure takes place beforehand. In the caval region near the sinus node, the conduction velocity of the excitation wave from the spontaneously beating sinus node was greater than that from the electrically driven atrium. The spontaneous action potential showed also a steeper rise than that produced by electrical stimulation. The mechanism responsible for this is discussed.
High-dose vitamin D3 during intensive-phase antimicrobial treatment of pulmonary tuberculosis: a double-blind randomised controlled trial
Authors: Adrian R Martineau, Peter M Timms, Graham H Bothamley, Yasmeen Hanifa, Kamrul Islam, Alleyna P Claxton, Geoffrey E Packe, John C Moore-Gillon, Mathina Darmalingam, Robert N Davidson, Heather J Milburn, Lucy V Baker, Richard D Barker, Nicholas J Woodward, Timothy R Venton, Korina E Barnes, Christopher J Mullett, Anna K Coussens, Clare M Rutterford, Charles A Mein, Geraint R Davies, Robert J Wilkinson, Vladyslav Nikolayevskyy, Francis A Drobniewski, Sandra M Eldridge, Christopher J Griffiths
Journal: The Lancet (2011)
TREATMENT OF VARICOSE ULCERS
Authors: A. D. Wright
Journal: BMJ (1930)

fromn an iiistitution in South-East London.These patients were in an early stage of measles, but enteritis was already present in all three instances.It is interesting to note that anotlher case, previously admitted from the same in- stitution, was also founid to be suffering from enteritis, though no definite evidence of measles could be found in this patient.It is thierefore possible that in this small group the enlteritis wvas a precursor andinot a complication of miieasles.As miglht be expected, the best resuilts were obtain-ed in the earlier stages of the disease.In the later stages a few cases showed some very enicouraging results, so that the treatmiient is iiot devoid of value even after somne days have elapsed before the case comiies uinder observation.Infants and very young subjects furnished the largest niumber of cases wlhich deriv-ed no apparent beniefit from treatmient, anld we have had under conisideration the quiestiont of the advisability of ineireasing the dosage in thlese Cases.Con ci olsio is}IS.1. Amidopyrin is a valuable adjuvant in the treatment of mzeasles.2. Its action is chiefly antipyretic, buit it appears to exerlise somle inifluenice onl the otlher symptoms of the dlisetise.3. Its -alute is greatest when given in the earlier stages, and in soine insta-nces it appears to modify the attack, but even in the later stages its use maav be followed by good results.4. Fromii time resuilts in ouir series of cases we a;r in a position to give a definite pronouncement oni the Claim, made by certaiin writers, that the drug is a specific " for measles.5. The treatment is conmparatively inexpensive, and very simple in its method of administration.In the dosage used by us it seems to be devoid of deleterious effects.6.The uise of amidopvrin miierits furtlier investigation over an extended series of cases.
Interleukin-27 displays interferon-γ-like functions in human hepatoma cells and hepatocytes
Authors: Herdis Bender, Monique Y. Wiesinger, Carolin Nordhoff, Caroline Schoenherr, Claude Haan, Stephan Ludwig, Ralf Weiskirchen, Nobuyuki Kato, Peter C. Heinrich, Serge Haan
Journal: Hepatology (2009)

Interleukin-27 (IL-27) is a cytokine belonging to the IL-6/IL-12 cytokine family. It is secreted by antigen-presenting cells, strongly acts on T cells, and also stimulates innate immune cells. In most studies, the effects of IL-27 on T cells were investigated; however, not much is known about possible effects of IL-27 on other cell types. IL-27 signals via the common IL-6-type cytokine receptor chain gp130 and the IL-27-specific chain WSX-1. Given the importance of gp130 in regulating liver responses such as the acute phase response or liver regeneration, we investigated whether IL-27 could also have a function in liver cells. We find that IL-27 stimulates hepatoma cells and hepatocytes by inducing a sustained signal transducer and activator of transcription (STAT)1 and STAT3 activation. Whereas the STAT3 mediated responses to IL-27 (gamma-fibrinogen and hepcidin induction) are not detectable, we observe an interferon-gamma (IFN-gamma)-like STAT1 response leading to the induction of interferon-regulated proteins such as STAT1, STAT2, interferon response factor (IRF)-1, IRF-9, myxovirus resistance A and guanylate binding protein 2.Our study provides evidence for a function of IL-27 in hepatoma cells and hepatocytes and shows that IL-27 responses are not restricted to the classical immune cells. Our results suggest that IL-27 exerts IFN-like functions in liver cells and that it can contribute to the antiviral response in these cells.
Independent risk factors for cumulative recurrence rate after first spontaneous pneumothorax
Authors: HL Lippert, O Lund, S Blegvad, HV Larsen
Journal: European Respiratory Journal (1991)

From 1975 until 1987, 122 patients without (Group I, mean age 34 yrs) and 20 with pre-existing lung disease (Group II, mean age 66 yrs) were treated for their first spontaneous pneumothorax. Mean follow-up was 5.2 yrs (max. 12.8 yrs). There were 32 chest X-ray verified recurrences, 72% occurring during the first 2 yrs. One, 5 and 10 yr cumulative recurrence freedoms +/- standard error in groups I and II combined were 85 +/- 3%, 75 +/- 4% and 69 +/- 5%, respectively. Using Cox regression analysis in groups I and II combined, pulmonary fibrosis, age greater than or equal to 60 yrs, and height/weight ratio were independent predictors of recurrence. Combinations of these risk factors identified four risk strata with 10 yr recurrence freedoms ranging from 83-0%. Independent predictors in group I alone were pulmonary fibrosis, age greater than or equal to 60 yrs, height/weight ratio, and nonsmoking, resulting in four risk strata with 10 yr recurrence freedoms ranging from 98-31%. Recurrences after first-time treated spontaneous pneumothorax showed a distinct time-related pattern and should accordingly be analysed as a time-related event. In both the total patient-population and in the group without pre-existing lung disease, independent predictors of recurrence were identified, which allowed the patients to be substratified into groups with widely different recurrence rates.
Downregulation of the serum response factor/miR-1 axis in the quadriceps of patients with COPD
Authors: Amy Lewis, Joanna Riddoch-Contreras, Samantha A Natanek, Anna Donaldson, William D-C Man, John Moxham, Nicholas S Hopkinson, Michael I Polkey, Paul R Kemp
Journal: Thorax (2011)

<h3>Rationale</h3> Muscle atrophy confers a poor prognosis in patients with chronic obstructive pulmonary disease (COPD), yet the molecular pathways responsible are poorly characterised. Muscle-specific microRNAs and serum response factor (SRF) are important regulators of muscle phenotype that contribute to a feedback system to regulate muscle gene expression. The role of these factors in the skeletal muscle dysfunction that accompanies COPD is unknown. <h3>Methods</h3> 31 patients with COPD and 14 healthy age-matched controls underwent lung and quadriceps function assessments, measurement of daily activity and a percutaneous quadriceps muscle biopsy. The expression of muscle-specific microRNAs, myosin heavy chains and components of the serum response factor signalling pathway were determined by qPCR. <h3>Results</h3> A reduction in expression of miR-1 (2.5-fold, p=0.01) and the myocardin-related transcription factors (MRTFs) A and B was observed in patients compared with controls (MRTF-A mRNA: twofold, p=0.028; MRTF-B mRNA: fourfold, p=0.011). miR-1 expression was associated with smoking history, lung function, fat-free mass index, 6 min walk distance and percentage of type 1 fibres. miR-133 and miR-206 were negatively correlated with daily physical activity. Insulin-like growth factor 1 mRNA was increased in the patients and miR-1 was negatively correlated with phosphorylation of the kinase Akt. Furthermore, the protein levels of histone deacetylase 4, another miR-1 target, were increased in the patients. <h3>Conclusions</h3> Downregulation of the activity of the MRTF-SRF axis and the expression of muscle-specific microRNAs, particularly miR-1, may contribute to COPD-associated skeletal muscle dysfunction.
Randomized controlled trials in medical education
Authors: Tom Parks
Journal: Journal of the Royal Society of Medicine (2009)

Calvert and Freementle1 advocate randomized controlled trials (RCTs) as a means of assessing educational strategies in undergraduate medical education. The RCT has become adopted as the most effective research tool currently available to avoid selection bias particularly during the evaluation of diagnostic or therapeutic interventions. But RCTs are not without weaknesses2 and to compensate journals now require stringent and transparent reporting of results.3

I remain concerned that RCTs should not, by default, be first choice of medical educationalists because their weaknesses may be unavoidable in the setting of a medical school. Particularly, eligibility criteria, concealment of allocations, implementation of randomization and blinding are likely to create problems. Are any groups of students excluded? At what stage during the course of their studies might students be randomized? While it might be possible to blind the analysts (to avoid detection bias), it would be almost impossible to blind the teacher (equivalent to the healthcare provider) and the student (equivalent to the patient). Thus any such trial is vulnerable not only to performance bias (the behaviour of the teacher applying novel techniques might be very different from their colleague giving a didactic lecture) but also placebo effects (the students might pay more attention and be more willing to turn up for novel teaching methods). Paradoxically, students might also be resistant to change and reluctant to participate in classes where new and unfamiliar teaching methods are tried further confounding the results.

But randomization is not the be all and end all of medical science.4 The answer may not simply be to borrow from the evidence-based strategies of clinical practice. Instead, the educational exposures that associate with good and bad clinical practice might be explored through carefully conducted observational studies. In short, good observational studies might supplant poor randomized studies in this setting.
P48 Telaprevir substantially improved SVR rates across all IL28B genotypes in the advance trial
Authors: G. M. Dusheiko, I. M. Jacobson, I. Catlett, S. George, S. Seepersaud, R. Ramachandran, K. Sussky, R. S. Kauffman, M. Botfield
Journal: Gut (2011)

<h3>Aim</h3> Single nucleotide polymorphisms (SNPs) near the IL28B gene region have been strongly associated with the likelihood of SVR in genotype 1 HCV patients treated with peginterferon/ribavirin (PR). During the evaluation of an exploratory diagnostic test that characterises genetic polymorphisms near the IL28B gene, the impact of rs1297860 on SVR in telaprevir (T)-based regimens in the ADVANCE trial was evaluated. <h3>Method</h3> IL28B genotype testing was performed according to a US FDA guidance governing use of de-identified leftover samples for in vitro diagnostic testing. The guidance requires a strict de-identification procedure that was carried out by an independent third party. Only specimens from the USA were used; and as non-Caucasian patients could not be de-identified in sufficient numbers, they were excluded from the study. <h3>Results</h3> The diagnostic assay developed provided consistent, unambiguous genotype calls and was considered suitable for research. 454/1088 (42%) patients had IL28B test results available. 150/454 (33%) were CC, 224/454 (49%) CT, and 80/454 (18%) TT. SVR rates for each subgroup by arm are shown in the Abstract P48 table 1. 72%, 54% and 48% of CC, CT and TT telaprevir patients, respectively had undetectable HCV RNA at weeks 4 and 12 (eRVR) compared with 16%, 2% and 0% of PR patients. Among eRVR telaprevir patients, 91% achieved SVR (97% of CC, 88% of CT, 85% of TT) with 24 weeks of therapy whereas 43% of non-eRVR telaprevir patients had SVR (63% of CC, 33% of CT, 46% of TT) with 48 weeks of therapy. <h3>Conclusion</h3> Telaprevir-based therapy improved eRVR and SVR rates across all IL28B genotypes. Specifically, telaprevir-based therapy more than doubled the rates of SVR in CT/TT patients, and substantially increased SVR rates in those with CC genotype, as compared with PR therapy alone. Non-attainment of eRVR was associated with lower SVR rates across all IL28B genotypes, with the largest decrement in CT/TT patients.
Optimisation of bronchial brachytherapy catheter placement with a modified airway stent
Authors: M. P. Kennedy, C. A. Jimenez, J. Chang, F. Fossella, G. A. Eapen, R. C. Morice
Journal: European Respiratory Journal (2008)

Brachytherapy is a modality of treatment available for lung cancer with tracheal involvement. Correct positioning of the brachytherapy catheter is vital to the optimisation of treatment effect and reduction of complications. Normal airway anatomy and tumour location can make this positioning difficult. The current study presents the case of a 65-yr-old male with invasive tracheal squamous cell carcinoma of the anterior main carina involving the proximal left and right bronchus. The patient was successfully treated with brachytherapy using a novel modified airway stent with a traversing suture for positioning and stabilising the brachytherapy catheters and maximisation of the radiation effect. This simple yet innovative modification of readily available bronchoscopic equipment permits approximation and fixation of a brachytherapy catheter to any part of the proximal airway. Further analysis of this technique, including a prospective controlled trial, is planned.
IFN-λs mediate antiviral protection through a distinct class II cytokine receptor complex
Authors: Sergei V. Kotenko, Grant Gallagher, Vitaliy V. Baurin, Anita Lewis-Antes, Meiling Shen, Nital K. Shah, Jerome A. Langer, Faruk Sheikh, Harold Dickensheets, Raymond P. Donnelly
Journal: Nature Immunology (2002)
XENical in the Prevention of Diabetes in Obese Subjects (XENDOS) Study
Authors: Jarl S. Torgerson, Jonathan Hauptman, Mark N. Boldrin, Lars Sjöström
Journal: Diabetes Care (2004)

OBJECTIVE—It is well established that the risk of developing type 2 diabetes is closely linked to the presence and duration of overweight and obesity. A reduction in the incidence of type 2 diabetes with lifestyle changes has previously been demonstrated. We hypothesized that adding a weight-reducing agent to lifestyle changes may lead to an even greater decrease in body weight, and thus the incidence of type 2 diabetes, in obese patients. RESEARCH DESIGN AND METHODS—In a 4-year, double-blind, prospective study, we randomized 3,305 patients to lifestyle changes plus either orlistat 120 mg or placebo, three times daily. Participants had a BMI ≥30 kg/m2 and normal (79%) or impaired (21%) glucose tolerance (IGT). Primary endpoints were time to onset of type 2 diabetes and change in body weight. Analyses were by intention to treat. RESULTS—Of orlistat-treated patients, 52% completed treatment compared with 34% of placebo recipients (P &amp;lt; 0.0001). After 4 years’ treatment, the cumulative incidence of diabetes was 9.0% with placebo and 6.2% with orlistat, corresponding to a risk reduction of 37.3% (P = 0.0032). Exploratory analyses indicated that the preventive effect was explained by the difference in subjects with IGT. Mean weight loss after 4 years was significantly greater with orlistat (5.8 vs. 3.0 kg with placebo; P &amp;lt; 0.001) and similar between orlistat recipients with impaired (5.7 kg) or normal glucose tolerance (NGT) (5.8 kg) at baseline. A second analysis in which the baseline weights of subjects who dropped out of the study was carried forward also demonstrated greater weight loss in the orlistat group (3.6 vs. 1.4 kg; P &amp;lt; 0.001). CONCLUSIONS—Compared with lifestyle changes alone, orlistat plus lifestyle changes resulted in a greater reduction in the incidence of type 2 diabetes over 4 years and produced greater weight loss in a clinically representative obese population. Difference in diabetes incidence was detectable only in the IGT subgroup; weight loss was similar in subjects with IGT and or NGT.