tbuckley/cabot-search huggingface dataset:
“Stepping-up” from methotrexate: a systematic review of randomised placebo controlled trials in patients with rheumatoid arthritis with an incomplete response to methotrexate
Authors: M C Hochberg, J K Tracy, R H Flores
Journal: Annals of the Rheumatic Diseases (2001)

Methotrexate is presently the standard disease modifying antirheumatic drug (DMARD) for patients with active rheumatoid arthritis (RA).1 Despite its short term efficacy in clinical trials and long term effectiveness in clinical practice,2-5 many patients continue to have signs and symptoms of active disease while taking a maximally tolerated dose.

Over the past decade there has been increasing interest in the use of combination therapy in patients with RA. Boers and Ramsden published the first systematic review of combination therapy in 1991 and identified two trials that provided moderate or strong evidence; neither of these studies used methotrexate.6 Tugwell and Boers updated this review in 1994 and identified four new trials that provided moderate or strong evidence; two of these trials used methotrexate in a parallel combination strategy.7Verhoeven and colleagues updated this review a second time in 1998 and identified 14 new trials published between August 1992 and July 1997.8 In their analysis, they combined these 14 new trials with the six previous trials and categorised the trials by the strategy of combination therapy: parallel, “step-up”, and “step-down”. Of these 20 trials, six used methotrexate in a parallel combination strategy, one of these trials used methotrexate in a step-down strategy, and two of these trials used methotrexate in a step-up strategy.8 Of the two trials which employed the step-up strategy in patients with an incomplete response to methotrexate, one compared the monoclonal anti-CD4 antibody cM-T412 with placebo and failed to show clinical efficacy,9whereas the other compared cyclosporin with placebo and did demonstrate additional efficacy with the combination compared with placebo.10 

With the advent of newer biological treatments directed at cytokines which play a part in the pathophysiology of RA, particularly tumour necrosis factor (TNF),11 additional trials of combination therapy based …
Identification of novel noninvasive markers for diagnosing nonalcoholic steatohepatitis and related fibrosis by data mining
Authors: Keito Yoshimura, Takeshi Okanoue, Hayao Ebise, Tsuyoshi Iwasaki, Masayuki Mizuno, Toshihide Shima, Junji Ichihara, Kazuto Yamazaki
Journal: Hepatology (2015)

It is important that patients with nonalcoholic steatohepatitis (NASH) are diagnosed and treated early to prevent serious complications, such as liver cirrhosis or hepatocellular carcinoma. However, current methods for NASH diagnosis are invasive given that they rely on liver biopsy, making early diagnosis difficult. In this study, we developed novel noninvasive markers for the diagnosis of NASH and NASH‐related fibrosis. A total of 132 Japanese patients with nonalcoholic fatty liver disease were included in this study. Blood samples were collected, and 261 biomolecules were quantified in serum. Using cluster and pathway analyses, we identified biomolecule modules connected to biological events that occur with disease progression to NASH. The modules were used as variables for diagnosis, leading to a NASH diagnostic marker associated with two biological events, that is, protective response to hepatic steatosis and hepatitis‐causing innate immune response. Regarding the NASH‐related fibrosis marker, immunological responses to hepatocyte injury were identified as a biological event. To develop diagnostic markers for NASH and NASH‐related fibrosis, specific biomolecules were selected from each biomolecule module. The former marker was obtained by averaging the levels of four biomolecules, whereas the latter was obtained by averaging the levels of two biomolecules. Both markers achieved a diagnostic accuracy of almost 0.9 of the area under the receiver operating characteristic curve, and the latter exhibited equivalent performance in an independent group of 62 prospectively recruited patients. Conclusion : We developed highly accurate markers for the diagnosis of both NASH and NASH‐related fibrosis (i.e., FM‐NASH index and FM‐fibro index, respectively). These markers may be used as an alternative diagnostic tool to liver biopsy. (H epatology 2016;63:462–473)
Noninvasive evaluation of hepatic steatosis and fibrosis in OSA patients at diagnosis
Authors: Maria Buttacavoli, Mirko Olivo, Roberto Virdone, Alessandra Castrogiovanni, Anna Maria Marotta, Vincenzo Bellia, Maria R. Bonsignore
Journal: European Respiratory Journal (2012)

In morbidly obese patients, non-alcoholic fatty liver disease (NAFLD) frequently occurs in patients with obstructive sleep apnea (OSA) compared to patients without OSA, and OSA may play a role in the pathogenesis of steatohepatitis. We non-invasively assessed hepatic steatosis (ultrasound) and fibrosis (Fibroscan elastometry) in 20 consecutive patients (mean age±SD: 48±11 yr; BMI: 34.9±5.9 kg/m²; 4 women) with newly diagnosed OSA and no history or serologic evidence of hepatic disease. Inclusion criteria were: alcohol consumption  40 U.I.); they were significantly younger (age 36.7±1.5 vs. 50.3±11.1 yr) and more obese (BMI 40.9±8.2 vs 33.8±5.0 kg/m²) than the rest of the sample. Hepatic steatosis (n=19) was mild in 4 patients, moderate in 1, and severe in 14; all patients with increased ALT showed severe steatosis. Severe steatosis occcured in most patients with MetS and tended to be associated with severe OSA. Fibroscan elastometry (n=14) gave an average value of 6.2±2.3 (normal  12). Therefore, noninvasive evaluation revealed a trend for hepatic steatosis to be associated with severe OSA and obesity, while hepatic fibrosis appeared absent or mild in our patients.
Antagonistic Effects of Vitamin D and Parathyroid Hormone on Lipoprotein Lipase in Cultured Adipocytes
Authors: UWE QUERFELD, MICHAEL M. HOFFMANN, GU[Combining Diaeresis]NTER KLAUS, FRANK EIFINGER, MARION ACKERSCHOTT, DIETRICH MICHALK, PHILIP A. KERN
Journal: Journal of the American Society of Nephrology (1999)

Abstract. The effects of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) (calcitriol) and parathyroid hormone (PTH) on synthesis and secretion of lipoprotein lipase (LPL) were studied in 3T3-L1 adipocytes. Expression of the vitamin D receptor was demonstrated by saturation kinetics with radiolabeled calcitriol. Incubation with calcitriol (10-8 M) for up to 4 d resulted in a time-dependent significant increase in heparin-releasable LPL activity (LPLa) accompanied by a significant increase in LPL mRNA. In contrast, incubation with intact (1-84) PTH (10-6 to 10-9 M) produced a time- and dose-dependent significant decrease in LPLa, but no change in LPL mRNA. The effect of PTH (24-h incubation, 10-8 M) could be prevented by the calcium channel blocker verapamil. Coincubation with both calcitriol and PTH at equimolar concentration (10-8 M) resulted in an increase in LPLa and LPL mRNA. These data indicate an antagonistic role for calcitriol and PTH in the regulation of LPL, possibly mediated by intracellular calcium, which may contribute to the alterations in lipoprotein metabolism occurring in uremia.
Etoposide and carboplatin: a highly effective combination in relapsed or refractory Wilms' tumor--a phase II study by the French Society of Pediatric Oncology.
Authors: F Pein, M F Tournade, J M Zucker, M Brunat-Mentigny, A Deville, P Boutard, F Dusol, J C Gentet, E Legall, F Mechinaud
Journal: Journal of Clinical Oncology (1994)

PURPOSE Since we had previously demonstrated encouraging efficacy of etoposide in patients with relapsed or refractory Wilms' tumor (WT), the likely synergism between etoposide and platinum compounds prompted us to conduct a phase II study of a combination with carboplatin. PATIENTS AND METHODS Twenty-six relapsed or refractory WT patients were included in a phase II study of two courses of combination etoposide 100 mg/m2/d for 5 days and carboplatin 160 mg/m2/d for 5 days, with a 21-day interval between the two courses. Initial stages were I (n = 2), II (n = 8), III (n = 6), IV (n = 6), V (n = 3), and unknown (n = 1). Sites of diseases were lung(s) (11 patients), abdomen-pelvis or liver or primary tumor (six patients), and multiple (eight patients). Histology was unfavorable in three of 26 patients. RESULTS Complete response (CR) was documented in eight patients and partial remission (PR) in 11 (overall response rate, 73%). Stable disease (SD) was observed in five patients and progressive disease (PD) in two. Thrombocytopenia (grade IV) was the major toxicity, and platelet transfusions were required in all but two patients. Grade III anemia and grade III to IV neutropenia were seen in 19 and 23, respectively, of 25 assessable first courses. Venoocclusive disease of the liver was fatal in one child who had undergone irradiation to the whole abdomen, 8 weeks before study. CONCLUSION Combination etoposide and carboplatin has impressive activity in refractory or relapsed WT at the cost of high-grade hematologic toxicity, especially thrombocytopenia. It is of great interest in second-line therapy, since eight of 26 patients are still alive in continuous CR (median follow-up duration, 40 months; range, 24 to 56). This combination deserves further investigation as first-line or consolidation treatment.
Respiratory rate from a pulse oximeter: A novel method to detect the acutely ill respiratory patient
Authors: Helmy Haja Mydin, Kimberley Scott, Graham Douglas
Journal: European Respiratory Journal (2013)

Background: Respiratory rate (RR) is a vital physiological marker and predictor of clinical deterioration. However, visual measurement is inaccurate and often not carried out (Goldhill, D.R. et al. Anaesthesia 1999; 54:529–34). We performed this study to ascertain the feasibility of pulse oximetry in objectively monitoring and recording RR in acutely ill respiratory patients.  Methods: We performed an observational clinical evaluation of the CE Marked Covidien Nellcor Respiration Rate System over two weeks. Patients in two acute respiratory wards had continuous monitoring via a system providing oxygen saturation (SpO2), pulse rate and RR using a single integrated sensor.  Results: N=66 (35M:31F). Five were diagnosed with asthma, one with pneumonia and 12 with exacerbation of COPD (three requiring non-invasive ventilation). We monitored and recorded clinical data including continuous RR, heart rate, SpO2 and duration of hypoxia. The data collated informed decisions on escalation of care. We will present selected data sets, similar to Figure 1.  Conclusions: The Covidien Nellcor RR System represents novel, non-invasive, easy-to-use technology for the measurement of RR within an acute clinical setting that could lead to enhanced patient safety. As RR is obtained unobtrusively from pulse oximetry, it can be added easily to the routine monitoring of patients’ observations without observational bias.
LSC 2013 abstract - Comparison of surfactant protein A in particles in exhaled air (PEx) and bronchoalveolar lavage
Authors: Mona Larstad, Ann-Charlotte Almstrand, Per Larsson, Ekaterina Mirgorodskaya, Gerdt Riise, Anna-Carin Olin
Journal: European Respiratory Journal (2013)

Introduction: Particles in exhaled air (PEx) are formed in the small airways during airway reopening after airway closure. Analysis of PEx offers noninvasive measurement of biomarkers from the respiratory tract lining fluid. Our objective was to investigate if SP-A and albumin in BAL are correlated to levels in PEx.

Methods: Consecutive stable patients undergoing bronchoscopy one year after lung transplantation (n=11), or for investigation of pulmonary fibrosis (n=2) and healthy volunteers (n=4) were included. The relative amount of SP-A and albumin in PEx were calculated adjusting for particle mass.

Results: There was no correlation between SP-A in PEx and SP-A in BAL, nor between albumin in PEx and BAL. SP-A was strongly correlated with albumin in PEx but in BAL there was a tendency towards a negative correlation. There was a trend for SP-A being higher and albumin lower in healthy controls compared with transplanted patients and those with IPF (SP-A: 2.5 vs. 2.1%, and albumin: 3.5 vs. 4.5%, respectively).

Table1. Medians and range of relative concentrations of SP-A and albumin in PEx and concentrations in BAL

![Figure][1] 



Conclusion: SP-A concentrations seem not to vary as much in PEx when compared to BAL, and average about half of the concentrations of albumin. There was no correlation between SP-A in PEx and BAL. This may reflect different origins of PEx and BAL, where PEx originates more strictly from the small airways. The dilution of SP-A in BAL is also an issue, and seem not to be overcome by adjusting for albumin levels.

 [1]: pending:yes
Abstract 9749: Impact of QRS Duration and Morphology on The Risk of Sudden Cardiac Death in Asymptomatic Patients with Aortic Stenosis: The Simvastatin and Ezetimibe in Aortic Stenosis Study
Authors: Anders M Greve, Eva Gerdts, Kurt Boman, Christa Gohlke-Baerwolf, Anne B Rossebø, Richard B Devereux, Lars Køber, Simon Ray, Ronnie Willenheimer, Kristian Kristian Wachtell
Journal: Circulation (2011)

Background: QRS duration and morphology are associated with poor prognosis in many different populations, but the predictive value, particularly of the risk of sudden cardiac death (SCD), in asymptomatic patients with aortic stenosis (AS) has not been well studied. Methods: Clinical examination, electrocardiography and echocardiography were obtained in 1,873 asymptomatic AS patients randomized to simvastatin/ezetimibe combination vs. placebo in the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study. Association of QRS duration, evaluated as a categorical variable of &lt;85 msec vs. 85-99 msec and ≥100 msec (excluding bundle branch block [BBB]) and QRS morphology in those with BBB, with the risk of cardiovascular morbidity and mortality was assessed by adjusting for biomarkers, clinical- and echocardiographic covariates as well as randomized treatment. Results: QRS data were available in 1,542 patients; followed for a mean of 4.3±0.8 years (6,631 patients-years of follow-up). QRS duration was &lt;85 msec in 900 patients (58.4%), 85-99 msec in 396 (25.7%), ≥100 msec without BBB in 144 (9.3%) and 102 (6.6%) had BBB. In multivariable analyses, those with QRS duration ≥100 msec had, compared to those with QRS duration &lt;85 msec, a 4.9-fold higher risk of sudden cardiac death (95% confidence interval [CI], 1.4 to 16.9, p=0.01) and a 2.7-fold higher risk of cardiovascular death (CI, 1.3 to 5.8, p=0.01). In univariate analyses, left BBB (n=43) was, compared to QRS duration &lt;85 msec, associated with a 3.8-fold higher risk heart failure and right BBB combined with left anterior fascicular block (n=20) with a 4.6-fold higher risk of myocardial infarction (both p&lt;0.05). Conclusion: QRS duration and morphology in asymptomatic patients with AS are independently associated with poor prognosis, particularly the risk of SCD. Figure : Incidence of Sudden Cardiac Death According to Baseline QRS Duration and Morphology: During 4.3 Years of Follow-Up.
In vitro activity of a new echinocandin, LY303366, and comparison with fluconazole, flucytosine and amphotericin B against Candida species† †This study was presented, in part, at the 37th ICAAC in Toronto, Canada, 28th September – 1st October 1997.
Authors: C.B. Moore, K.L. Oakley, D.W. Denning
Journal: Clinical Microbiology and Infection (2001)
Patients can self monitor oral anticoagulation, study shows
Authors: Susan Mayor
Journal: BMJ (2015)

Patients can self monitor and self manage oral anticoagulation, a UK community based study has shown.1

The study, reported in the British Journal of General Practice , included 296 patients requiring oral anticoagulation who had bought a device to self monitor their international normalised ratio (INR). Most patients (97%) had warfarin prescribed, and this was for a range of conditions including thrombosis (35.8%), having a mechanical heart valve (32.8%), atrial fibrillation (23.0%), and …
Use of medicines and prevalence of co-morbid diseases in subjects with and without COPD in Sweden
Authors: Sven-Arne Jansson, Helena Backman, Eva Rönmark, Bo Lundbäck, Anne Lindberg
Journal: European Respiratory Journal (2013)

Background  Chronic obstructive pulmonary disease (COPD) is one of the most common diseases with substantial morbidity and mortality.   Aim  To analyse the use of medicines due to respiratory and co-morbid diseases and to analyse the prevalence of co-morbid diseases in a cohort of subjects with and without COPD in Sweden.   Methods  A cohort of subjects was identified in earlier clinical examinations of the general population of Northern Sweden within the Obstructive Lung Disease in Northern Sweden (OLIN) Studies. The cohort consisted initially of 993 subjects fulfilling criteria for COPD and an age- and gender matched control sample of same size without obstructive lung function impairment. Since 2005, these subjects have been invited to yearly interviews and examinations. This analysis is based on resource use data collected in 2006 (COPD: n=772, 78% of the initial cohort, and non-COPD: n=802, 81%).   Results  The use of respiratory medicines increased with severity grade of COPD (mild 30%, moderate 52% and severe + very severe 85%). The same trend was seen for medicines due to co-morbid diseases. The proportion of subjects that used medicines for at least one other disease was higher among subjects with COPD compared to non-COPD subjects, 78% vs. 73%, p=0.05. The prevalence of co-morbid diseases was high among subjects with COPD. However, the only disease that was statistically more common among subjects with COPD compared to non-COPD subjects was depression (p=0.001).   Conclusions  The use of medicines due to co-morbid diseases was higher among subjects with COPD. These results indicate that not only respiratory conditions but also co-morbid diseases contribute to high societal costs for COPD.
Abstract 3170: Inferior Infarct Patching Reduces Mitral Regurgitation, Decreases Infarct Expansion, and Maintains Global and Remote-Zone Contractility: An Echo-MRI Study
Authors: Miguel Chaput, Judy Hung, Fred Holmvang, J. L Guerrero, Francois Tournoux, Suzanne Sullivan, Robert A Levine
Journal: Circulation (2007)

Infarct (MI) patching has been shown to reduce mitral regurgitation (MR) in chronic MI models, but its local and global effects on the LV require further study. We tested the hypothesis that MI patching with papillary muscle (PM)repositioning not only reduces MR but also limits infarct expansion and progression of global LV dysfunction. Methods. Fourteen sheep with MIs created in a standard vascular territory as confirmed by first-pass gadolinium (Gd) MRI were studied at baseline, acutely post-MI and at 3 months by sonomicrometry, 3D echo and MRI. Animals were randomized to control versus treatment with an adjustable patch device to reposition the inferior PM (n=7 each). MI size was assessed by Gd-enhanced MRI and local wall motion by echo-derived tissue velocities. Results. MR was reduced chronically in all patch animals (vena contracta=0.08 vs 0.5 cm, p&lt;0.001). At 3 months, despite end-diastolic dilatation in both groups (127±20 vs 128±16 mL, p=0.91, 1.4±0.1 x baseline), end-systolic volumes were smaller (71±9 vs 100±21 mL, p=0.05) and EF higher (43±11 vs 24±10%, p=0.02) in the treated group, with better maintained preload recruitable stroke work (41±5 vs 33±3, p=0.01). Infarct expansion at 3 months was reduced by patching (infarct/LV surface area=22±5 vs 41±6%, p=0.001; figure ). Remote zone contractile function was also improved by patching (strain=20±5 vs 11±4%, p=0.03; tissue velocity=3.5±0.7 vs 1.8±0.6 cm/s, p=0.05). Conclusion. Despite continued LV remodeling, inferior infarct patching leads to long-term decreased MR and better preserved global LV function, with both diminished expansion of the restrained infarct and preserved contractility of the remote myocardium.
Association between coronary artery disease (CAD) and heart failure and age in obstructive sleep apnoea (OSA) patients
Authors: Robert Plywaczewski, Anna Czyzak-Gradkowska, Monika Targowska, Przemyslaw Bielen, Pawel Sliwinski
Journal: European Respiratory Journal (2014)

Cardiovascular diseases are most frequent complications of untreated OSA. The aim of this study was to compare OSA pts with CAD and without CAD. We studied 1048 OSA pts with moderate or severe disease (AHI - 42.1±21), mean age - 56.1±10.4 years, BMI - 34.4±6,4 kg/m 2, Epworth score - 11.3±5.8 points, mean SaO2 -90.6±5.8%. We found 812 pts without CAD (77.5%; group 1) and 236 pts with CAD (22.5%; group 2). Comparison of both groups is shown in table.

View this table:



Logistic regression analysis revealed that: heart failure (OR- 4.43; 95%CI – 2.74-7.15; p  60 vs ≤ 60 years (OR- 2.38; 95%CI – 1.82-3.12;p  125 vs ≤ 125 pg/ml (OR – 1.84; 95%CI – 1.27-2.67; p=0.001) and diabetes (OR-1.47; 95%CI – 1.007-2.14; p=0.045) were independent predictors of CAD after adjusting for AH, stroke, AF, COPD, BMI > 30 vs ≤30 and hyperuricaemia.

Conclusions: Coronary artery disease was frequent in OSA pts (more than 20%). We found strongest association between heart failure and age and CAD in OSA patients.
Electron Microscopic Observations on Cytoplasmic Components of Transplantable Hepatomas in Mice&lt;xref ref-type="fn" rid="fn1"&gt;2&lt;/xref&gt;
Authors: Nancy L. Trotter
Journal: JNCI Journal of the National Cancer Institute (1963)

Journal Article Electron Microscopic Observations on Cytoplasmic Components of Transplantable Hepatomas in Mice Get access Nancy L. Trotter Nancy L. Trotter Department of Anatomy, College of Physicians and Surgeons, Columbia UniversityNew York, New York Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 30, Issue 1, January 1963, Pages 113–133, https://doi.org/10.1093/jnci/30.1.113 Published: 01 January 1963 Article history Received: 02 July 1962 Published: 01 January 1963
Speech breathing pattern analysis in adults with a self reported history of asthma
Authors: Rokhsaneh Tehrany, Anne Bruton, Anna Barney
Journal: European Respiratory Journal (2012)

Background : While speech and breathing patterns are known to alter in acute episodes of respiratory disorders like asthma, it is not known if they alter in respiratory pathology, during stable periods of the disease.   Aims and objectives:  To compare speech breathing patterns in healthy adults and those with a self reported history of asthma.   Methods:  Eleven adults with a self reported history of asthma (mean age = 29) and 29 9healthy9 adults (mean age = 34) with no history of respiratory disease were recruited from the University of Southampton. Breathing patterns were recorded non-invasively using Respiratory Inductive Plethysmography during 4 minutes each of quiet breathing, and 3 speech tasks: reading, describing and conversation. Offline analysis was performed where 6 breathing parameters were extracted; inspiration and expiration time (T I , T E ), breath cycle time (Ttot), inspiration and expiration magnitude (IM, EM), and respiratory rate (RR).   Results:  Inspiration time was significantly shorter at the 95% level in the asthma group (mean: 0.52,  sd : 0.07) compared with the 9healthy9 participants (mean 0.66,  sd  0.12) (t: 3.27,  p  = 0.002). Although no statistically significant differences were found in other parameters, the asthma group had a higher mean RR during all speech tasks compared to the healthy group.   Conclusion:  These preliminary findings suggest that ventilatory patterns during speech in adults with a self-reported history of asthma are characterised by a shorter T I  and faster RR compared to 9healthy9 participants. Research with larger samples is needed to confirm these initial findings, as breathing patterns during structured tasks like speech could be useful for monitoring lung health.