tbuckley/cabot-search huggingface dataset:
Low residue or normal diet in Crohn's disease: a prospective controlled study in Italian patients.
Authors: S Levenstein, C Prantera, C Luzi, A D'Ubaldi
Journal: Gut (1985)

Seventy patients with non-stenosing Crohn9s disease were randomly assigned to follow a low residue diet or a normal Italian diet for a mean of 29 months. The two groups were comparable at the onset in various measures of disease severity and diet. Patients complied well with the diet prescriptions, the low residue group eating a mean of 8.1 portions a week of fibre containing foods and the liberalized group a mean of 26.6 portions (p less than 0.005). There was no difference in outcome between the two groups, including symptoms, need for hospitalisation, need for surgery, new complications, nutritional status, or postoperative recurrence. Eighty six per cent of patients eating ad libitum and 65% of patients who avoided roughage eliminated one or more permitted foods because of subjective intolerance. Lifting of dietary restrictions, which results in a more appetizing and nutritious diet, does not cause symptomatic deterioration or precipitate intestinal obstruction in Crohn9s disease.
Changing Patterns of Asthma Hospitalization Among Children: 1979 to 1987
Authors: Peter J. Gergen, Kevin B. Weiss
Journal: JAMA (1990)

The National Hospital Discharge Survey was used to evaluate the trends in asthma hospitalizations among children under International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM): 1979 to 1987. During this period, asthma hospitalizations among children aged 0 to 17 years increased 4.5% per annum (95% confidence interval [Cl], 2% to 7.1%). The increase was largest among 0 to 4 year olds, 5.0% per annum (95% Cl, 3.4% to 6.7%), vs 2.9% per annum (95% Cl, -0.3% to 6.2%) observed among 5 to 17 year olds. Among children aged 0 to 4 years, blacks had approximately 1.8 times the increase of whites. During this time, total hospitalizations decreased -4.6% (95% Cl, -6.6% to -2.5%), while admissions for lower respiratory tract disease had a statistically insignificant decrease: -1.3%. Acute and chronic/unspecified bronchitis hospitalizations decreased -6.1% (95% Cl, -9.4% to -2.7%), but this decrease did not begin until 1983. Thus, a shift in coding from bronchitis to asthma does not seem to fully explain the increase.
Timing of Onset of CKD-Related Metabolic Complications
Authors: Olivier Moranne, Marc Froissart, Jerome Rossert, Cedric Gauci, Jean-Jacques Boffa, Jean Philippe Haymann, Mona Ben M’rad, Christian Jacquot, Pascal Houillier, Benedicte Stengel, Bruno Fouqueray
Journal: Journal of the American Society of Nephrology (2008)

Chronic kidney disease (CKD) guidelines recommend evaluating patients with GFR <60 ml/min per 1.73 m(2) for complications, but little evidence supports the use of a single GFR threshold for all metabolic disorders. We used data from the NephroTest cohort, including 1038 adult patients who had stages 2 through 5 CKD and were not on dialysis, to study the occurrence of metabolic complications. GFR was measured using renal clearance of (51)Cr-EDTA (mGFR) and estimated using two equations derived from the Modification of Diet in Renal Disease study. As mGFR decreased from 60 to 90 to <20 ml/min per 1.73 m(2), the prevalence of hyperparathyroidism increased from 17 to 85%, anemia from 8 to 41%, hyperphosphatemia from 1 to 30%, metabolic acidosis from 2 to 39%, and hyperkalemia from 2 to 42%. Factors most strongly associated with metabolic complications, independent of mGFR, were younger age for acidosis and hyperphosphatemia, presence of diabetes for acidosis, diabetic kidney disease for anemia, and both male gender and the use of inhibitors of the renin-angiotensin system for hyperkalemia. mGFR thresholds for detecting complications with 90% sensitivity were 50, 44, 40, 39, and 37 ml/min per 1.73 m(2) for hyperparathyroidism, anemia, acidosis, hyperkalemia, and hyperphosphatemia, respectively. Analysis using estimated GFR produced similar results. In summary, this study describes the onset of CKD-related complications at different levels of GFR; anemia and hyperparathyroidism occur earlier than acidosis, hyperkalemia, and hyperphosphatemia.
Effect of Expedited Treatment of Sex Partners on Recurrent or Persistent Gonorrhea or Chlamydial Infection
Authors: Matthew R. Golden, William L.H. Whittington, H. Hunter Handsfield, James P. Hughes, Walter E. Stamm, Matthew Hogben, Agnes Clark, Cheryl Malinski, Jennifer R.L. Helmers, Katherine K. Thomas, King K. Holmes
Journal: New England Journal of Medicine (2005)

Many sex partners of persons with gonorrhea or chlamydial infections are not treated, which leads to frequent reinfections and further transmission.We randomly assigned women and heterosexual men with gonorrhea or chlamydial infection to have their partners receive expedited treatment or standard referral. Patients in the expedited-treatment group were offered medication to give to their sex partners, or if they preferred, study staff members contacted partners and provided them with medication without a clinical examination. Patients assigned to standard partner referral were advised to refer their partners for treatment and were offered assistance notifying partners. The primary outcome was persistent or recurrent gonorrhea or chlamydial infection in patients 3 to 19 weeks after treatment.Persistent or recurrent gonorrhea or chlamydial infection occurred in 121 of 931 patients (13 percent) assigned to standard partner referral and 92 of 929 (10 percent) assigned to expedited treatment of sexual partners (relative risk, 0.76; 95 percent confidence interval, 0.59 to 0.98). Expedited treatment was more effective than standard referral of partners in reducing persistent or recurrent infection among patients with gonorrhea (3 percent vs. 11 percent, P=0.01) than in those with chlamydial infection (11 percent vs. 13 percent, P=0.17) (P=0.05 for the comparison of treatment effects) and remained independently associated with a reduced risk of persistent or recurrent infection after adjustment for other predictors of infection at follow-up (relative risk, 0.75; 95 percent confidence interval, 0.57 to 0.97). Patients assigned to expedited treatment of sexual partners were significantly more likely than those assigned to standard referral of partners to report that all of their partners were treated and significantly less likely to report having sex with an untreated partner.Expedited treatment of sex partners reduces the rates of persistent or recurrent gonorrhea or chlamydial infection.
Primary atypical mycobacteriosis of the intestine: a report of three cases.
Authors: K Fujisawa, H Watanabe, K Yamamoto, T Nasu, Y Kitahara, M Nakano
Journal: Gut (1989)

Primary atypical mycobacteriosis of the lung is comparatively common but primary atypical mycobacteriosis of the intestine had not been described previously in the English literature. We have treated three such patients with antituberculous drugs and the clinicopathological findings and course are described. We suggest that these findings may belong to a new clinical entity.
Comparison of Power Between Randomized Discontinuation Design and Upfront Randomization Design on Progression-Free Survival
Authors: Pingfu Fu, Afshin Dowlati, Mark Schluchter
Journal: Journal of Clinical Oncology (2009)

Enrichment based on molecular characteristics has emerged as an important inclusion criterion in phase II trials of targeted anticancer agents. In this study, we evaluate a well-described method of population enrichment by tumor growth characteristics in the early development stage of targeted cytostatic agents.For some solid tumors, such as pancreatic carcinoma, using a time-to-event end point (eg, time to disease progression) to evaluate the efficacy of a cytostatic agent in a phase II trial is more relevant than clinical response by Response Evaluation Criteria in Solid Tumors. In this setting, we compared the power of the randomized discontinuation and upfront randomization designs under two previously proposed tumor growth models for treatment effect when the end point is time-to-event.By selecting patients with more homogeneous tumor growth characteristics, the randomized discontinuation design is more efficient than the upfront randomization design when treatment benefit is restricted to slow-growing tumors. Under a model where only a subset of patients expressing the molecular target are sensitive to the agent, the randomized discontinuation design is more powerful than the upfront randomization design when the treatment effect is small; and vice versa when the treatment effect is moderate to large.For selected targeted agents where a bioassay to select patients expressing the specific molecular target is not available, the randomized discontinuation design is a feasible alternative patient enrichment strategy in certain disease settings and provides a reasonable platform to evaluate drugs before phase III testing.
Therapeutic antiviral T cells noncytopathically clear persistently infected microglia after conversion into antigen-presenting cells
Authors: Jasmin Herz, Kory R. Johnson, Dorian B. McGavern
Journal: The Journal of Experimental Medicine (2015)

Several viruses can infect the mammalian nervous system and induce neurological dysfunction. Adoptive immunotherapy is an approach that involves administration of antiviral T cells and has shown promise in clinical studies for the treatment of peripheral virus infections in humans such as cytomegalovirus (CMV), Epstein-Barr virus (EBV), and adenovirus, among others. In contrast, clearance of neurotropic infections is particularly challenging because the central nervous system (CNS) is relatively intolerant of immunopathological reactions. Therefore, it is essential to develop and mechanistically understand therapies that noncytopathically eradicate pathogens from the CNS. Here, we used mice persistently infected from birth with lymphocytic choriomeningitis virus (LCMV) to demonstrate that therapeutic antiviral T cells can completely purge the persistently infected brain without causing blood–brain barrier breakdown or tissue damage. Mechanistically, this is accomplished through a tailored release of chemoattractants that recruit antiviral T cells, but few pathogenic innate immune cells such as neutrophils and inflammatory monocytes. Upon arrival, T cells enlisted the support of nearly all brain-resident myeloid cells (microglia) by inducing proliferation and converting them into CD11c+ antigen-presenting cells (APCs). Two-photon imaging experiments revealed that antiviral CD8+ and CD4+ T cells interacted directly with CD11c+ microglia and induced STAT1 signaling but did not initiate programmed cell death. We propose that noncytopathic CNS viral clearance can be achieved by therapeutic antiviral T cells reliant on restricted chemoattractant production and interactions with apoptosis-resistant microglia.
Associations of Ambient Air Pollution with Chronic Obstructive Pulmonary Disease Hospitalization and Mortality
Authors: Wen Qi Gan, J. Mark FitzGerald, Chris Carlsten, Mohsen Sadatsafavi, Michael Brauer
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

Rationale: Ambient air pollution has been suggested as a risk factor for chronic obstructive pulmonary disease (COPD). However, there is a lack of longitudinal studies to support this assertion.Objectives: To investigate the associations of long-term exposure to elevated traffic-related air pollution and woodsmoke pollution with the risk of COPD hospitalization and mortality.Methods: This population-based cohort study included a 5-year exposure period and a 4-year follow-up period. All residents aged 45–85 years who resided in Metropolitan Vancouver, Canada, during the exposure period and did not have known COPD at baseline were included in this study (n = 467,994). Residential exposures to traffic-related air pollutants (black carbon, particulate matter <2.5 μm in aerodynamic diameter, nitrogen dioxide, and nitric oxide) and woodsmoke were estimated using land-use regression models and integrating changes in residences during the exposure period. COPD hospitalizations and deaths during the follow-up period were identified from provincial hospitalization and death registration databases.Measurements and Main Results: An interquartile range elevation in black carbon concentrations (0.97 × 10−5/m, equivalent to 0.78 μg/m3 elemental carbon) was associated with a 6% (95% confidence interval, 2–10%) increase in COPD hospitalizations and a 7% (0–13%) increase in COPD mortality after adjustment for covariates. Exposure to higher levels of woodsmoke pollution (tertile 3 vs. tertile 1) was associated with a 15% (2–29%) increase in COPD hospitalizations. There were positive exposure–response trends for these observed associations.Conclusions: Ambient air pollution, including traffic-related fine particulate pollution and woodsmoke pollution, is associated with an increased risk of COPD.
Single-Drug Vinblastine As Salvage Treatment for Refractory or Relapsed Anaplastic Large-Cell Lymphoma: A Report From the French Society of Pediatric Oncology
Authors: Laurence Brugières, Helene Pacquement, Marie-Cecile Le Deley, Guy Leverger, Patrick Lutz, Catherine Paillard, Andre Baruchel, Didier Frappaz, Brigitte Nelken, Laurence Lamant, Catherine Patte
Journal: Journal of Clinical Oncology (2009)

To evaluate the efficacy of vinblastine for relapsed/refractory anaplastic large-cell lymphoma (ALCL).Data were reviewed on all 36 patients included prospectively in the French database for pediatric ALCL who were treated with vinblastine (6 mg/m(2)/wk) for resistant primary disease (one), a first relapse (15), or subsequent relapses (20). Fifteen patients had undergone hematopoietic stem-cell transplantation (HSCT) for a previous relapse.Six patients were not evaluable for response, 25 (83%) of 30 evaluable patients achieved a complete remission (CR), and five experienced progressive disease. Among the 31 patients who achieved a CR with vinblastine or before its initiation, six patients were treated with HSCT and 25 with vinblastine alone (median duration, 14 months). Overall, nine of 25 patients treated with vinblastine alone have remained in CR (median, 7 years since the end of treatment), and 16 patients have relapsed. Vinblastine was still efficient for subsequent relapses. With a median follow-up of 9.2 years, 12 patients have died (four as a result of toxicity after HSCT and eight as a result of disease), and 24 patients are alive (15 following treatment with single-agent vinblastine for the last event). Five-year overall survival is 65% (95% CI, 48% to 79%), and 5-year event-free survival is 30% (95% CI, 17% to 47%).Vinblastine is highly efficient in relapsed ALCL and may produce durable remissions. The optimal treatment duration still has to be assessed. These results should be borne in mind when designing future phase II studies with the targeted therapies directed against anaplastic lymphoma kinase.
Revisiting the Yeast PPR Proteins—Application of an Iterative Hidden Markov Model Algorithm Reveals New Members of the Rapidly Evolving Family
Authors: Kamil A. Lipinski, Olga Puchta, Vineeth Surendranath, Marek Kudla, Pawel Golik
Journal: Molecular Biology and Evolution (2011)

Pentatricopeptide repeat (PPR) proteins are the largest known RNA-binding protein family, and are found in all eukaryotes, being particularly abundant in higher plants. PPR proteins localize mostly to mitochondria and chloroplasts, and many were shown to modulate organellar genome expression on the posttranscriptional level. Although the genomes of land plants encode hundreds of PPR proteins, only a few have been identified in Fungi and Metazoa. As the current PPR motif profiles are built mainly on the basis of the predominant plant sequences, they are unlikely to be optimal for detecting fungal and animal members of the family, and many putative PPR proteins in these genomes may remain undetected. In order to verify this hypothesis, we designed a hidden Markov model-based bioinformatic tool called Supervised Clustering-based Iterative Phylogenetic Hidden Markov Model algorithm for the Evaluation of tandem Repeat motif families (SCIPHER) using sequence data from orthologous clusters from available yeast genomes. This approach allowed us to assign 12 new proteins in Saccharomyces cerevisiae to the PPR family. Similarly, in other yeast species, we obtained a 5-fold increase in the detection of PPR motifs, compared with the previous tools. All the newly identified S. cerevisiae PPR proteins localize in the mitochondrion and are a part of the RNA processing interaction network. Furthermore, the yeast PPR proteins seem to undergo an accelerated divergent evolution. Analysis of single and double amino acid substitutions in the Dmr1 protein of S. cerevisiae suggests that cooperative interactions between motifs and pseudoreversion could be the force driving this rapid evolution.
EFFECTS OF THE ORAL DIRECT RENIN INHIBITOR ALISKIREN ON PLASMA BNP CONCENTRATION IN PATIENTS WITH SYMPTOMATIC HEART FAILURE ACCORDING TO BACKGROUND DOSE OF ACE INHIBITOR
Authors: John JV McMurray, Claudio Gimpelewicz, Roberto Latini, Aldo P. Maggioni, Bertram Pitt, Scott D. Solomon, Anil Verma, Beverly A. Smith, Deborah L. Keefe, Margaret F. Prescott, James D. Lewsey
Journal: Journal of the American College of Cardiology (2010)
Syndromic Validity of Apathy in Alzheimer’s Disease
Authors: Sergio E. Starkstein, Gustavo Petracca, Erán Chemerinski, Janus Kremer
Journal: American Journal of Psychiatry (2001)

OBJECTIVE: The study examined the usefulness and clinical correlates of specific diagnostic criteria for apathy in Alzheimer’s disease. Whereas apathy is a frequent behavioral change in patients with Alzheimer’s disease, the lack of standardized diagnostic criteria may explain the wide discrepancies in estimates of the frequency and demographic and clinical correlates of apathy. METHOD: A consecutive series of 319 patients who met the criteria for probable Alzheimer’s disease established by the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer’s Disease and Related Disorders Association, 117 patients who met the DSM-IV criteria for depression without dementia, and 36 healthy individuals were assessed with a structured psychiatric interview. On the basis of modified Marin’s criteria for apathy, they were classified into groups with or without apathy. RESULTS: Apathy was diagnosed in 37% of the 319 Alzheimer’s disease patients, compared to none of the healthy comparison subjects. In 24% of the Alzheimer’s disease sample, apathy coexisted with either dysthymic disorder or major depressive disorder, whereas 13% had apathy without depression. Apathy was diagnosed in 32% of the depressed nondemented patients, mostly in those with major depressive disorder. Apathy in Alzheimer’s disease was significantly associated with severe impairments in activities of daily living and cognitive functions, older age, and poor awareness of behavioral and cognitive changes. CONCLUSIONS: This study provides partial validation of specific clinical criteria for apathy in Alzheimer’s disease.
Blood pressure lowering by pioglitazone. Evidence for a direct vascular effect.
Authors: T A Buchanan, W P Meehan, Y Y Jeng, D Yang, T M Chan, J L Nadler, S Scott, R K Rude, W A Hsueh
Journal: Journal of Clinical Investigation (1995)

To examine potential mechanisms for the blood pressure-lowering action of the thiazolidinedione compound, pioglitazone (PIO), we studied the effects of the drug on blood pressure and insulin action in vivo and on vascular tissue in vitro. In vivo, PIO lowered blood pressure in fructose-fed and chow-fed rats to an extent that could not be explained by alterations in fasting plasma insulin or free magnesium concentrations or by alterations in whole-body insulin sensitivity. In vitro, PIO caused significant blunting of the contractile responses of aortic rings to NE, arginine vasopressin (AVP), and potassium chloride; the blunting of responses to NE was maintained after removal of the endothelium. To assess the potential importance of extracellular calcium to the vasodepressor effect of PIO, we measured contractile responses to NE in the absence of calcium, and then after acute restoration of calcium in the presence of NE. PIO had no effect on the contractile response in the absence of calcium. By contrast, PIO blunted by 42% the contractile response that occurred when the extracellular calcium supply was acutely restored in the presence of NE, suggesting that the blunting was mediated by blockade of calcium uptake by vascular smooth muscle. Such an effect was confirmed in cultured a7r5 vascular smooth muscle cells, which exhibited a brisk increase in intracellular calcium in response to AVP that was blocked by PIO in a dose-dependent fashion. Our data indicate that PIO has a direct vascular effect that appears to be mediated at least in part by inhibition of agonist-mediated calcium uptake by vascular smooth muscle. The direct vascular effect may contribute to the blood pressure-lowering actions of PIO in vivo, because that effect could not be explained by alterations in whole-body insulin sensitivity.
Predictive value of diminutive colonic adenoma trial: The PREDICT trial
Authors: Philip Schoenfeld, Javaid Shad, Eric Ormseth, Walter Coyle, Brooks Cash, James Butler, William Schindler, Walter J. Kikendall, Christopher Furlong, Leslie H. Sobin, Christine M. Hobbs, David Cruess, Douglas Rex
Journal: Clinical Gastroenterology and Hepatology (2003)
The influence of complex ICS/LABA therapy on oxygen consumption in COPD patients
Authors: Yuriy Feshchenko, Liudmyla Iashyna, Svitlana Opimakh
Journal: European Respiratory Journal (2014)

Background: Hypoxemia is one of the unfavorable consequences of chronic obstructive pulmonary disease (COPD). Combine therapy with inhaled corticosteroids (ICS) and long-acting beta2-agonists (LABA) improves lung function and health status in COPD patients. As such treatment has impact on oxygen consumption?

Objectives: This study aimed to investigate the influence of complex ICS/LABA therapy on oxygen consumption in COPD patients.

Methods: This was an observation of 10 patients (average age (63.6±4.1) years) with stable COPD, mean FEV1 (37.2±3.5)% of predicted, to whom complex ICS/LABA therapy (fluticasone propionate 1000 mcg daily, salmeterol 100 mcg daily) was prescribed. Oxygen content in the exhaled air was evaluated before and after 3 months therapy, specifically end-tidal O2 fraction (FETO2) and expired O2 fraction (FEO2). Data are presented as mean±SD.

Results : We observed statistically significant improvement in oxygen exchange of the patients: reduced of FETO2 from (16.3±0.6) to (15.8±0.7) %, FEO2 from (17.8±0.5) to (17.4±0.5) % after the end of the 3 month therapy, for both p<0.05. We assume that in average COPD patient inhales atmospheric air with the O2 concentration 20.85 % and exhales air with an average O2 concentration 17.8 %, that metabolized 3.05 % oxygen before treatment. After the therapy oxygen consumption became 3.45 % that 13 % more than at baseline.

Conclusion: The possible way of positive health changes under combine ICS/LABA therapy in COPD patients may be the improvement of oxygen delivery and consumption.The place of oxygen content in the exhaled air analysis on oxygen consumption control may be the subject of future research.
Intestinal immune homeostasis is regulated by the crosstalk between epithelial cells and dendritic cells
Authors: Monica Rimoldi, Marcello Chieppa, Valentina Salucci, Francesca Avogadri, Angelica Sonzogni, Gianluca M Sampietro, Angelo Nespoli, Giuseppe Viale, Paola Allavena, Maria Rescigno
Journal: Nature Immunology (2005)