tbuckley/cabot-search huggingface dataset:
Relationship of serum elastin peptide level to single breath transfer factor for carbon monoxide in French coal miners
Authors: C. Frette, M. P. Jacob, S. M. Wei, J. P. Bertrand, P. Laurent, F. Kauffmann, Q. T. Pham
Journal: Thorax (1997)

Clinical and epidemiological studies have given discordant results on the usefulness of the level of circulating elastin peptide (EP), a potential marker of both elastin destruction (a key phenomenon in pulmonary emphysema) and neosynthesis, for assessing structural changes in the lung extracellular matrix. The aim of the present study was to explore the relationship between levels of EP and forced expiratory volume in one second (FEV1) and single breath transfer factor for carbon monoxide (TLCO and KCO) in coal miners.The study population comprised 227 working coal miners aged 34-50 years consisting of 75 miners heavily exposed to underground coal dust with pulmonary radiographs classified as 0/1 or 1/0 by the International Labour Office classification, 75 exposed miners with radiographs classified as normal (0/0), and 77 miners slightly exposed to coal dust with normal radiographs. The subjects answered a standardised questionnaire and performed spirometric tests and a carbon monoxide (CO) transfer test.No association was observed between EP levels and % predicted FEV1 (or FEV1/FVC). The level of EP increased significantly with decreased % predicted TLCO (r = -0.20). Miners in the lowest % predicted KCO quintile had higher EP levels than the rest (3.28 (1.37) vs 2.47 (1.16)). A significantly lower EP level was observed in miners with radiographs classified as 1/0 or 0/1, especially in those with round opacities, compared with miners with a normal radiograph, and in current smokers compared with the rest.The results of this study suggest that the level of EP may reflect some remodelling activity in emphysema and lung fibrosis.
Role of appendix in the development of inflammatory bowel disease in TCR-alpha mutant mice.
Authors: A Mizoguchi, E Mizoguchi, C Chiba, A K Bhan
Journal: The Journal of Experimental Medicine (1996)

T cell receptor-alpha mutant mice (TCR-alpha-/-), created by gene targeting of the TCR-alpha gene in embryonic stem cells, spontaneously develop inflammatory bowel disease (IBD) resembling human ulcerative colitis. Since gut-associated lymphoid tissue is likely to play an important role in the development of chronic intestinal inflammation, we examined the changes in the appendix lymphoid follicle (ALF) and Peyer's patches (PP) in these mice. We found the structure of the ALF to be remarkably similar to that of the PP in the small intestine; in both instances, lymphoid follicles covered by surface epithelium (dome-formation) were found. The amount of proliferation in the lymphoid follicles of the appendix estimated by in vivo incorporation of 5-bromo-2'deoxyuridine was more than two times that of PP in TCR-alpha-/- mice. ELISPOT assay showed an increase of IgA, IgG1, and IgG2a, but not IgM-secreting B cells in ALF of TCR-alpha-/- mice compared to TCR-alpha+/- control mice. Furthermore, TCR-alpha-/- mice revealed an increase of autoantibody-producing B cells against the cytoskeletal protein tropomyosin in ALF as compared to PP. When TCR-alpha-/- mice underwent appendectomy at a young age (3-5 wk), the number of mesenteric lymph nodes cells at 6-7 mo were markedly less than in the sham-operated TCR-alpha-/- mice. Furthermore, appendectomy at 1 mo of age suppressed the development of IBD, with only 3.3% of these mice developing IBD in the 6-7-mo period of observation. In contrast, approximately 80% of controls, including the sham-operated TCR-alpha-/- mice, developed IBD during this period. These results suggest that ALF, rather than PP, is the priming site of cells involved in the disease process and plays an important role in the development of IBD in TCR-alpha-/- mice.
Association Between Prenatal Exposure to Poliovirus Infection and Adult Schizophrenia
Authors: Jaana Suvisaari, Jari Haukka, Antti Tanskanen, Tapani Hovi, Jouko Lönnqvist
Journal: American Journal of Psychiatry (1999)

The authors' goal was to determine whether there is an association between prenatal exposure to poliovirus infection and later development of schizophrenia.All Finnish patients born between 1951 and 1969 with discharge diagnoses of schizophrenia (N = 13,559) were identified from the Finnish Hospital Discharge Register. Information on the monthly number of cases of paralytic poliomyelitis was obtained for each province in Finland. The authors analyzed the incidence of births of individuals who later developed schizophrenia by using a Poisson regression model with year and place of birth, age, sex, season of birth, and smoothed incidence of poliomyelitis in different gestational periods as explanatory variables.An association between the incidence of poliomyelitis and the incidence of births 5 months later of individuals who later developed schizophrenia was observed. Without controlling for seasonality, the effect was significant throughout the second trimester.Second-trimester exposure to poliovirus infection may increase the risk for the later development of schizophrenia.
Assessing Site-Interdependent Phylogenetic Models of Sequence Evolution
Authors: Nicolas Rodrigue, Hervé Philippe, Nicolas Lartillot
Journal: Molecular Biology and Evolution (2006)

In recent works, methods have been proposed for applying phylogenetic models that allow for a general interdependence between the amino acid positions of a protein. As of yet, such models have focused on site interdependencies resulting from sequence-structure compatibility constraints, using simplified structural representations in combination with a set of statistical potentials. This structural compatibility criterion is meant as a proxy for sequence fitness, and the methods developed thus far can incorporate different site-interdependent fitness proxies based on other measurements. However, no methods have been proposed for comparing and evaluating the adequacy of alternative fitness proxies in this context, or for more general comparisons with canonical models of protein evolution. In the present work, we apply Bayesian methods of model selection—based on numerical calculations of marginal likelihoods and posterior predictive checks—to evaluate models encompassing the site-interdependent framework. Our application of these methods indicates that considering site-interdependencies, as done here, leads to an improved model fit for all data sets studied. Yet, we find that the use of pairwise contact potentials alone does not suitably account for across-site rate heterogeneity or amino acid exchange propensities; for such complexities, site-independent treatments are still called for. The most favored models combine the use of statistical potentials with a suitably rich site-independent model. Altogether, the methodology employed here should allow for a more rigorous and systematic exploration of different ways of modeling explicit structural constraints, or any other site-interdependent criterion, while best exploiting the richness of previously proposed models.
Resistance to adefovir dipivoxil in lamivudine resistant chronic hepatitis B patients treated with adefovir dipivoxil
Authors: J E Yeon
Journal: Gut (2006)

Adefovir dipivoxil (ADV) is a potent nucleotide analogue against both the wild-type and lamivudine (LMV) resistant hepatitis B virus (HBV). The cumulative incidence of ADV resistant mutations in the nucleoside/-tide treatment naive chronic hepatitis B patient (CHB) at weeks 48, 96, and 144 was 0, 0.8-3%, and approximately 5.9%, respectively.The aim of this study was to characterise the genotypic and phenotypic mutation profiles to ADV in 67 LMV resistant CHB patients who were treated with ADV.Serum HBV DNA was quantified by real time polymerase chain reaction. The ADV mutant was detected using matrix assisted laser desorption/ionisation time of flight mass spectrometry based genotyping assays, termed restriction fragment mass polymorphism (RFMP).RFMP analysis revealed that a total of 11 amino acid substitutions developed in the rt domain of the HBV polymerase in nine patients. The cumulative incidence of genotypic ADV resistance at months 12 and 24 was 6.4% and 25.4%, respectively. The rtA181V, rtN236T, and rtA181T mutations were detected in five, four, and two of the 67 patients at treatment months 12-17, 3-19, and 7-20, respectively. Serial quantification of serum HBV DNA revealed that two patients with the rtA181V mutation, with or without the rtN236T mutation, and one patient with the rtA181T mutation displayed HBV DNA rebound.Emergence of the ADV mutation in LMV resistant patients who are treated with ADV appeared to present earlier and more frequently than was reported in previous studies on nucleoside/-tide treatment naive patients.
Pharmacogenetics during standardised initiation of thiopurine treatment in inflammatory bowel disease
Authors: U Hindorf
Journal: Gut (2006)

<b>Background:</b> Firm recommendations about the way thiopurine drugs are introduced and the use of thiopurine methyltransferase (TPMT) and metabolite measurements during treatment in inflammatory bowel disease (IBD) are lacking. <b>Aim:</b> To evaluate pharmacokinetics and tolerance after initiation of thiopurine treatment with a fixed dosing schedule in patients with IBD. <b>Patients:</b> 60 consecutive patients with Crohn's disease (n = 33) or ulcerative colitis (n = 27) were included in a 20 week open, prospective study. <b>Methods:</b> Thiopurine treatment was introduced using a predefined dose escalation schedule, reaching a daily target dose at week 3 of 2.5 mg azathioprine or 1.25 mg 6-mercaptopurine per kg body weight. TPMT and ITPA genotypes, TPMT activity, TPMT gene expression, and thiopurine metabolites were determined. Clinical outcome and occurrence of adverse events were monitored. <b>Results:</b> 27 patients completed the study per protocol, while 33 were withdrawn (early protocol violation (n = 5), TPMT deficiency (n = 1), thiopurine related adverse events (n = 27)); 67% of patients with adverse events tolerated long term treatment on a lower dose (median 1.32 mg azathioprine/kg body weight). TPMT activity did not change during the 20 week course of the study but a significant decrease in TPMT gene expression was found (TPMT/huCYC ratio; p = 0.02). Patients with meTIMP concentrations &gt;11 450 pmol/8×10<sup>8</sup> red blood cells during steady state at week 5 had an increased risk of developing myelotoxicity (odds ratio = 45.0; p = 0.015). <b>Conclusions:</b> After initiation of thiopurine treatment using a fixed dosing schedule, no general induction of TPMT enzyme activity occurred, though TPMT gene expression decreased. The development of different types of toxicity was unpredictable, but we found that measurement of meTIMP early in the steady state phase helped to identify patients at risk of developing myelotoxicity.
Vasoactivity of AG014699, a Clinically Active Small Molecule Inhibitor of Poly(ADP-ribose) Polymerase: a Contributory Factor to Chemopotentiation <i>In vivo</i>?
Authors: Majid Ali, Brian A. Telfer, Cian McCrudden, Martin O'Rourke, Huw D. Thomas, Marzieh Kamjoo, Suzanne Kyle, Tracy Robson, Chris Shaw, David G. Hirst, Nicola J. Curtin, Kaye J. Williams
Journal: Clinical Cancer Research (2009)

Abstract Purpose: Poly(ADP-ribose) polymerase (PARP) plays an important role in DNA repair, and PARP inhibitors can enhance the activity of DNA-damaging agents in vitro and in vivo. AG014699 is a potent PARP inhibitor in phase II clinical development. However, the range of therapeutics with which AG014699 could interact via a DNA-repair based mechanism is limited. We aimed to investigate a novel, vascular-based activity of AG014699, underlying in vivo chemosensitization, which could widen its clinical application. Experimental Design: Temozolomide response was analyzed in vitro and in vivo. Vessel dynamics were monitored using “mismatch” following the administration of perfusion markers and real-time analysis of fluorescently labeled albumin uptake in to tumors established in dorsal window chambers. Further mechanistic investigations used ex vivo assays of vascular smooth muscle relaxation, gut motility, and myosin light chain kinase (MLCK) inhibition. Results: AG014699 failed to sensitize SW620 cells to temozolomide in vitro but induced pronounced enhancement in vivo. AG014699 (1 mg/kg) improved tumor perfusion comparably with the control agents nicotinamide (1 g/kg) and AG14361 (forerunner to AG014699; 10 mg/kg). AG014699 and AG14361 relaxed preconstricted vascular smooth muscle more potently than the standard agent, hydralazine, with no impact on gut motility. AG014699 inhibited MLCK at concentrations that relaxed isolated arteries, whereas AG14361 had no effect. Conclusion: Increased vessel perfusion elicited by AG014699 could increase tumor drug accumulation and therapeutic response. Vasoactive concentrations of AG014699 do not cause detrimental side effects to gut motility and may increase the range of therapeutics with which AG014699 could be combined with for clinical benefit. (Clin Cancer Res 2009;15(19):6106–12)
An Official ATS Statement: Grading the Quality of Evidence and Strength of Recommendations in ATS Guidelines and Recommendations
Authors: Holger J. Schünemann, Roman Jaeschke, Deborah J. Cook, William F. Bria, Ali A. El-Solh, Armin Ernst, Bonnie F. Fahy, Michael K. Gould, Kathleen L. Horan, Jerry A. Krishnan, Constantine A. Manthous, Janet R. Maurer, Walter T. McNicholas, Andrew D. Oxman, Gordon Rubenfeld, Gerard M. Turino, Gordon Guyatt
Journal: American Journal of Respiratory and Critical Care Medicine (2006)

Grading the strength of recommendations and the quality of underlying evidence enhances the usefulness of clinical practice guidelines. Professional societies and other organizations, including the American Thoracic Society (ATS), should reach consensus about whether they will use one common grading system and which of the numerous grading systems they would apply across all guidelines. The profusion of guideline grading systems confuses consumers of guidelines, and undermines the value of the grading exercise in conveying a transparent message. In response to this dilemma, the international GRADE working group has developed an approach that is useful for many guideline contexts, and that several national and international organizations have adopted. The GRADE system classifies recommendations as strong or weak, according to the balance of the benefits and downsides (harms, burden, and cost) after considering the quality of evidence. The quality of evidence reflects the confidence in estimates of the true effects of an intervention, and the system classifies quality of evidence as high, moderate, low, or very low according to factors that include the study methodology, the consistency and precision of the results, and the directness of the evidence. On recommendation of the ATS Documents Development and Implementation Committee, the ATS adopted the GRADE approach for its guidelines in line with many other organizations that have recently chosen the GRADE approach. This article informs ATS guideline developers, investigators, and those interpreting future ATS guidelines that follow the GRADE approach about the methodology and applicability of ATS guidelines and recommendations.
Effects of CPAP on body weight in patients with obstructive sleep apnoea: a meta-analysis of randomised trials
Authors: L. F. Drager, A. R. Brunoni, R. Jenner, G. Lorenzi-Filho, I. M. Bensenor, P. A. Lotufo
Journal: Thorax (2014)

The impact of obstructive sleep apnoea (OSA) treatment with CPAP on weight is not clear. This meta-analysis was designed to assess whether OSA treatment with CPAP promotes changes in body mass index (BMI) and weight.We searched PubMed, SCOPUS and Cochrane Central Register electronic databases through 1 October 2013 (including papers in press at that time), without language restrictions. We identified randomised trials of CPAP versus controls with a minimum treatment duration of 4 weeks that objectively measured BMI. Data were independently abstracted and reviewed by two investigators using a standardised protocol.We included a total of 3181 patients from 25 randomised trials that measured BMI and weight. All studies enrolled mainly overweight and obese patients. The fixed-effects meta-analysis revealed that CPAP promoted significant increase on BMI (Hedges' g=0.14, 95% CI 0.07 to 0.21, I(2)=16.2%) and weight (Hedges' g=0.17, 95% CI 0.10 to 0.24, I(2)=0%). The funnel plot revealed low risk of publication bias. Meta-regression analyses including age, gender, baseline BMI, baseline weight, OSA severity, CPAP compliance, use of sham CPAP, study duration, study design (crossover/parallel), study origin (Western/Eastern), recommendation for dietary changes or physical activity, revealed that no single predictor influenced the main outcome for weight. Baseline weight was a predictor of increased BMI after CPAP.OSA treatment with CPAP promotes significant increase in BMI and weight. Additional therapies for body weight reduction must be recommended for overweight or obese patients with OSA initiated on CPAP.
Early closure of a multicenter randomized clinical trial of endoscopic stenting versus surgery for stage IV left-sided colorectal cancer
Authors: J. van Hooft, P. Fockens, A. Marinelli, R. Timmer, A. van Berkel, P. Bossuyt, W. Bemelman
Journal: Endoscopy (2008)

See also: Commentaire de travail de J. E. van Hooft et al., pp. 184Endoscopy 2008; 40(03): 355-355DOI: 10.1055/s-0032-1306813
Interventional bronchoscopy for tuberculous tracheobronchial stenosis
Authors: S-Y Low, A Hsu, P Eng
Journal: European Respiratory Journal (2004)

This study investigated the use of interventional bronchoscopic techniques in the management of patients with symptomatic tracheobronchial stenosis from tuberculosis. The current authors evaluated their experience with interventional bronchoscopic techniques in 21 consecutive patients at the Singapore General Hospital, Singapore, from November 1994 to March 2001. All patients underwent rigid bronchocopy using the Dumon rigid ventilating bronchosope under general anaesthesia. A combination of techniques was used (mechanical or balloon dilatation, Nd-YAG laser and stenting using the Dumon stent). The mean+/-SD increase in luminal diameter of the tracheal lesions was from 4.5+/-2.5 mm pre-procedure to 11.9+/-1.7 mm post-procedure, whereas that for the mainstem bronchi stenosis was from 2.6+/-1.0 mm to 8.3+/-2.4 mm. All patients had immediate relief of symptoms post-intervention. Two patients who presented with acute respiratory failure could be weaned off mechanical ventilation immediately post-procedure. At the end of the study period, 52% (11 out of 21) remained asymptomatic. Bronchoscopic intervention provided immediate symptomatic relief in all of the studied patients. However, repeated sessions may be required to maintain this improvement. It is concluded that interventional bronchoscopic techniques are useful in the management of patients with tracheobronchial stenosis from tuberculosis.
Chemotactic Factor Inactivator in Normal Human Serum
Authors: Jeffrey L. Berenberg, Peter A. Ward
Journal: Journal of Clinical Investigation (1973)

Normal human serum contains an inactivator of chemotactic factors for neutrophilic leukocytes. The chemotactic factor inactivator (CF-I) remains soluble when serum is fractionated with ammonium sulfate (at 45% saturation), directly and irreversibly inactivates chemotactic factors, and it has a broad spectrum of activity as indicated by its inactivation of the chemotactic fragments of human C3 and C5 (third and fifth components of complement), C567, and the bacterial chemotactic factor derived from Escherichia coli. CF-I appears as a biphasic activity according to preparative techniques of sucrose density ultracentrifugation, electrophoresis, and gel filtration. Studies on the interaction of CF-I with the radiotagged C5 chemotactic fragment fail to reveal evidence for irreversible binding as the basis for inactivation. CF-I varies from the anaphylatoxin inactivator in several physical-chemical respects, but evidence does not permit a conclusive statement about the relationship of the two inactivators. CF-I may function as a regulator of inflammatory responses.
Obesity and obstructive sleep apnea in children less than eight Years of age
Authors: Reshma Amin, Dennison Lai, Allison Zweerink, Indra Narang
Journal: European Respiratory Journal (2013)

Obstructive sleep apnea complicates obesity. The number of obese children   We retrospectively reviewed obese children,   We compared 22 obese with 22 lean children. There were 55% males. The mean age ± SD of each of the obese and lean cohorts was 5.12 ± 2.1 years. The mean ± SD BMI for obese and lean children was 31.69 ± 5.20 and 15.73 ± 3.13, p   Obese children had more severe OSA AHI, lower oxygen saturation nadir and higher respiratory rates than lean children. These data suggest that obese children have increased cardiorespiratory compromise during sleep than their age matched lean peers. Early diagnosis and intervention is paramount to reducing co-morbidity in obese children.
Time constant histograms from the forced expired volume signal: a clinical evaluation
Authors: JP Revelly, F Feihl, T Liebling, C Perret
Journal: European Respiratory Journal (1989)

We evaluated a multicompartment analysis of forced expiration, based on modelling the lung as a set of twenty parallel compartments emptying exponentially with time constants ranging from 0.1-10 s; the forced expired volume signal was represented by a histogram showing the fraction of forced vital capacity as a function of compartmental time constants. We applied this technique to 80 healthy and 12 asthmatic subjects. The histograms computed from three consecutive forced expirations were poorly reproducible in 18 of the 80 healthy and 2 of the 12 asthmatic subjects. In the asthmatics, the time constant histograms conveyed no additional information on bronchial obstruction, beyond that already present in standard spirometric indices. A simulation study showed a high sensitivity of the histograms to the truncation of the terminal part of forced expiration. We conclude that the usefulness of the time constant histogram technique appears doubtful.