tbuckley/cabot-search huggingface dataset:
Large Pre- and Postexercise Rapid-Acting Insulin Reductions Preserve Glycemia and Prevent Early- but Not Late-Onset Hypoglycemia in Patients With Type 1 Diabetes
Authors: Matthew D. Campbell, Mark Walker, Michael I. Trenell, Djordje G. Jakovljevic, Emma J. Stevenson, Richard M. Bracken, Stephen C. Bain, Daniel J. West
Journal: Diabetes Care (2013)

OBJECTIVE To examine the acute and 24-h glycemic responses to reductions in postexercise rapid-acting insulin dose in type 1 diabetic patients. RESEARCH DESIGN AND METHODS After preliminary testing, 11 male patients (24 ± 2 years, HbA1c 7.7 ± 0.3%; 61 ± 3.4 mmol/mol) attended the laboratory on three mornings. Patients consumed a standardized breakfast (1 g carbohydrate ⋅ kg−1 BM; 380 ± 10 kcal) and self-administered a 25% rapid-acting insulin dose 60 min prior to performing 45 min of treadmill running at 72.5 ± 0.9% VO2peak. At 60 min postexercise, patients ingested a meal (1 g carbohydrate ⋅ kg−1 BM; 660 ± 21 kcal) and administered a Full, 75%, or 50% rapid-acting insulin dose. Blood glucose concentrations were measured for 3 h postmeal. Interstitial glucose was recorded for 20 h after leaving the laboratory using a continuous glucose monitoring system. RESULTS All glycemic responses were similar across conditions up to 60 min postexercise. After the postexercise meal, blood glucose was preserved under 50%, but declined under Full and 75%. Thence at 3 h, blood glucose was highest under 50% (50% [10.4 ± 1.2] vs. Full [6.2 ± 0.7] and 75% [7.6 ± 1.2 mmol ⋅ L−1], P = 0.029); throughout this period, all patients were protected against hypoglycemia under 50% (blood glucose ≤3.9; Full, n = 5; 75%, n = 2; 50%, n = 0). Fifty percent continued to protect patients against hypoglycemia for a further 4 h under free-living conditions. However, late-evening and nocturnal glycemia were similar; as a consequence, late-onset hypoglycemia was experienced under all conditions. CONCLUSIONS A 25% pre-exercise and 50% postexercise rapid-acting insulin dose preserves glycemia and protects patients against early-onset hypoglycemia (≤8 h). However, this strategy does not protect against late-onset postexercise hypoglycemia.
Extra- and intra-ovarian factors in polycystic ovary syndrome: impact on oocyte maturation and embryo developmental competence
Authors: J. Qiao, H. L. Feng
Journal: Human Reproduction Update (2010)

BACKGROUNDPolycystic ovary syndrome (PCOS) is a common metabolic dysfunction and heterogeneous endocrine disorder in women of reproductive age. Although patients with PCOS are typically characterized by increased numbers of oocytes retrieved during IVF, they are often of poor quality, leading to lower fertilization, cleavage and implantation rates, and a higher miscarriage rate.
Tumor Angiogenesis Is Associated with Plasma Levels of Stromal-Derived Factor-1α in Patients with Multiple Myeloma
Authors: Sally K. Martin, Andrea L. Dewar, Amanda N. Farrugia, Noemi Horvath, Stan Gronthos, L. Bik To, Andrew C.W. Zannettino
Journal: Clinical Cancer Research (2006)

Multiple myeloma is an incurable hematologic malignancy characterized by increased bone marrow angiogenesis and extensive lytic bone disease. We have previously shown that elevated levels of stromal-derived factor-1alpha (SDF-1alpha) in peripheral blood plasma are associated with osteolysis in multiple myeloma patients. We have now examined whether SDF-1alpha levels also correlate with angiogenesis.We examined the contribution of multiple myeloma plasma cell-derived SDF-1alpha in the stimulation of in vitro angiogenesis using a tube formation assay. We also collected trephine and peripheral blood plasma samples from patients with multiple myeloma to analyze microvessel density and SDF-1alpha levels, respectively.We show that multiple myeloma plasma cell line-derived conditioned medium containing SDF-1alpha stimulates in vitro angiogenesis. In addition, in a large cohort of patients with multiple myeloma and its precursor condition monoclonal gammopathy of undetermined significance, we confirm previous findings that plasma cell burden correlates with both angiogenesis and plasma levels of SDF-1alpha. We now extend these observations and show the novel finding that peripheral blood plasma levels of SDF-1alpha positively correlate with the degree of bone marrow angiogenesis in multiple myeloma and monoclonal gammopathy of undetermined significance patients.High levels of SDF-1alpha produced by multiple myeloma plasma cells promote osteolysis and bone marrow angiogenesis. Therefore, we propose that inhibition of SDF-1alpha may be an effective mechanism by which angiogenesis and osteolysis can be reduced in multiple myeloma patients.
Selection criteria for intensive care unit referral of lung cancer patients: a pilot study
Authors: Anne-Claire Toffart, Carola Alegria Pizarro, Carole Schwebel, Linda Sakhri, Clemence Minet, Michaël Duruisseaux, Elie Azoulay, Denis Moro-Sibilot, Jean-François Timsit
Journal: European Respiratory Journal (2014)

The decision-making process for the intensity of care delivered to patients with lung cancer and organ failure is poorly understood, and does not always involve intensivists. Our objective was to describe the potential suitability for intensive care unit (ICU) referral of lung cancer in-patients with organ failures. We prospectively included consecutive lung cancer patients with failure of at least one organ admitted to the teaching hospital in Grenoble, France, between December 2010 and October 2012. Of 140 patients, 121 (86%) were evaluated by an oncologist and 49 (35%) were referred for ICU admission, with subsequent admission for 36 (73%) out of those 49. Factors independently associated with ICU referral were performance status ⩽2 (OR 10.07, 95% CI 3.85–26.32), nonprogressive malignancy (OR 7.00, 95% CI 2.24–21.80), and no explicit refusal of ICU admission by the patient and/or family (OR 7.95, 95% CI 2.39–26.37). Factors independently associated with ICU admission were the initial ward being other than the lung cancer unit (OR 6.02, 95% CI 1.11–32.80) and an available medical ICU bed (OR 8.19, 95% CI 1.48–45.35). Only one-third of lung cancer patients with organ failures were referred for ICU admission. The decision not to consider ICU admission was often taken by a non-intensivist, with advice from an oncologist rather than an intensivist.
Recurrent and persistent respiratory tract viral infections in patients with primary hypogammaglobulinemia
Authors: Leena Kainulainen, Tytti Vuorinen, Kaisu Rantakokko-Jalava, Riikka Österback, Olli Ruuskanen
Journal: Journal of Allergy and Clinical Immunology (2010)

The occurrence of respiratory tract viral infections in patients with primary hypogammaglobulinemia has not been studied.We conducted a prospective 12-month follow-up study of respiratory tract infections in 12 adult patients with primary hypogammaglobulinemia.Nasal swab samples and induced sputum samples were taken at the onset of acute respiratory tract infection and every 3 months thereafter. Samples were tested for bacteria and viruses. PCR tests were performed for 15 respiratory tract viruses. In case the results for rhinovirus were positive, follow-up nasal swab samples were taken every 2 weeks until rhinoviral PCR results became negative. Patients completed symptom diaries, which were collected every month. The spouses of the patients served as healthy control subjects.During the 12-month period, the 12 patients had 65 episodes of acute respiratory tract infections, and the 11 spouses had 12 acute episodes (P < .001). Respiratory tract viruses were found in sputum in 54% of the infections. Rhinovirus was the most common virus. In more than half of our patients, rhinoviral PCR results stayed positive for more than 2 months. The most long-acting persistence with the same rhinovirus was 4 months.Despite adequate immunoglobulin replacement therapy, patients with primary hypogammaglobulinemia have increased susceptibility to respiratory tract viral infections. Rhinoviral infections are frequent and prolonged.
2015 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis
Authors: Jasvinder A. Singh, Kenneth G. Saag, S. Louis Bridges, Elie A. Akl, Raveendhara R. Bannuru, Matthew C. Sullivan, Elizaveta Vaysbrot, Christine McNaughton, Mikala Osani, Robert H. Shmerling, Jeffrey R. Curtis, Daniel E. Furst, Deborah Parks, Arthur Kavanaugh, James O'Dell, Charles King, Amye Leong, Eric L. Matteson, John T. Schousboe, Barbara Drevlow, Seth Ginsberg, James Grober, E. William St.Clair, Elizabeth Tindall, Amy S. Miller, Timothy McAlindon
Journal: Arthritis & Rheumatology (2015)

Objective To develop a new evidence‐based, pharmacologic treatment guideline for rheumatoid arthritis (RA). Methods We conducted systematic reviews to synthesize the evidence for the benefits and harms of various treatment options. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology to rate the quality of evidence. We employed a group consensus process to grade the strength of recommendations (either strong or conditional). A strong recommendation indicates that clinicians are certain that the benefits of an intervention far outweigh the harms (or vice versa). A conditional recommendation denotes uncertainty over the balance of benefits and harms and/or more significant variability in patient values and preferences. Results The guideline covers the use of traditional disease‐modifying antirheumatic drugs (DMARDs), biologic agents, tofacitinib, and glucocorticoids in early (&lt;6 months) and established (≥6 months) RA. In addition, it provides recommendations on using a treat‐to‐target approach, tapering and discontinuing medications, and the use of biologic agents and DMARDs in patients with hepatitis, congestive heart failure, malignancy, and serious infections. The guideline addresses the use of vaccines in patients starting/receiving DMARDs or biologic agents, screening for tuberculosis in patients starting/receiving biologic agents or tofacitinib, and laboratory monitoring for traditional DMARDs. The guideline includes 74 recommendations: 23% are strong and 77% are conditional. Conclusion This RA guideline should serve as a tool for clinicians and patients (our two target audiences) for pharmacologic treatment decisions in commonly encountered clinical situations. These recommendations are not prescriptive, and the treatment decisions should be made by physicians and patients through a shared decision‐making process taking into account patients’ values, preferences, and comorbidities. These recommendations should not be used to limit or deny access to therapies.
Effect of epidural stimulation of the lumbosacral spinal cord on voluntary movement, standing, and assisted stepping after motor complete paraplegia: a case study
Authors: Susan Harkema, Yury Gerasimenko, Jonathan Hodes, Joel Burdick, Claudia Angeli, Yangsheng Chen, Christie Ferreira, Andrea Willhite, Enrico Rejc, Robert G Grossman, V Reggie Edgerton
Journal: The Lancet (2011)
Glutathione<i>S</i>-transferase m1 and t1 null genotypes increase susceptibility to idiosyncratic drug-induced liver injury
Authors: M. Isabel Lucena, Raúl J. Andrade, Carmen Martínez, Eugenia Ulzurrun, Elena García‐Martín, Yolanda Borraz, M. Carmen Fernández, Manuel Romero‐Gomez, Agustin Castiella, Ramón Planas, Joan Costa, Sandra Anzola, José A. G. Agúndez
Journal: Hepatology (2008)

Individual vulnerability to drug-induced liver injury (DILI) might result from deficiencies in the detoxification process, which determines the level of exposure to the reactive metabolite. We evaluated whether a genetically determined reduction in the ability to detoxify electrophilic compounds, such as that expected among individuals with glutathione S-transferase (GST) null genotypes, might play a role in determining the risk for DILI and its clinical expression. Genomic DNA from 154 patients (74 men, 80 women; mean age, 53 years) with a diagnosis of DILI as assessed with the Council for International Organizations of Medical Science scale and 250 sex- and age-matched healthy controls were analyzed. A multiplex polymerase chain reaction–based method was used to detect GSTM1 and GSTT1 gene deletions. Carriers of double GSTT1-M1 null genotypes had a 2.70-fold increased risk of developing DILI compared with noncarriers (odds ratio 2.70, 95% confidence interval 1.45-5.03; P = 0.003). The odds ratio for DILI patients receiving antibacterials, and NSAIDs were 3.52 (P = 0.002), and 5.61 (P = 0.001), respectively. Patients with amoxicillin-clavulanate hepatotoxicity (n = 32) had a 2.81-fold increased risk (P = 0.037). Patients classified by the combined GSTT1 and GSTM1 null genotypes did not differ with regard to the type of injury, clinical presentation, or outcome, except for the predominance of women in the combined null genotype (P < 0.001). Conclusion: The double-null genotype for GSTT1 and GSTM1 might play a role in determining the susceptibility to develop DILI, as a general mechanism that occurs regardless of the type of drug involved, and predominantly in women. (HEPATOLOGY 2008;48:588–596.)
Evolution of Nuclear Retinoic Acid Receptor Alpha (RAR ) Phosphorylation Sites. Serine Gain Provides Fine-Tuned Regulation
Authors: E. Samarut, I. Amal, G. V. Markov, R. Stote, A. Dejaegere, V. Laudet, C. Rochette-Egly
Journal: Molecular Biology and Evolution (2011)

The human nuclear retinoic acid (RA) receptor alpha (hRARα) is a ligand-dependent transcriptional regulator, which is controlled by a phosphorylation cascade. The cascade starts with the RA-induced phosphorylation of a serine residue located in the ligand-binding domain, S(LBD), allowing the recruitment of the cdk7/cyclin H/MAT1 subcomplex of TFIIH through the docking of cyclin H. It ends by the subsequent phosphorylation by cdk7 of an other serine located in the N-terminal domain, S(NTD). Here, we show that this cascade relies on an increase in the flexibility of the domain involved in cyclin H binding, subsequently to the phosphorylation of S(LBD). Owing to the functional importance of RARα in several vertebrate species, we investigated whether the phosphorylation cascade was conserved in zebrafish (Danio rerio), which expresses two RARα genes: RARα-A and RARα-B. We found that in zebrafish RARαs, S(LBD) is absent, whereas S(NTD) is conserved and phosphorylated. Therefore, we analyzed the pattern of conservation of the phosphorylation sites and traced back their evolution. We found that S(LBD) is most often absent outside mammalian RARα and appears late during vertebrate evolution. In contrast, S(NTD) is conserved, indicating that the phosphorylation of this functional site has been under ancient high selection constraint. This suggests that, during evolution, different regulatory circuits control RARα activity.
Pre-operative evaluation of lung function test results
Authors: C. T. Bolliger, A. Brunelli, A. Charloux
Journal: European Respiratory Journal (2010)

Pre-operative evaluation of lung function test resultsTo the Editors:The European Respiratory Society/European Society of Thoracic Surgeons joint clinical guidelines on fitness for radical therapy in lung cancer patients (surgery and chemoradiotherapy) were published in the July 2009 issue of the European Respiratory Journal [1].This comprehensive and very important document provides guidelines for the risk evaluation of candidates for lung cancer surgery.We fully agree that the lung function variables forced expiratory volume in 1 s (FEV1) and diffusing capacity of the lung for carbon monoxide (DL,CO), together with exercise capacity, are essential components in the risk stratification.We do not, however, agree on the recommended interpretation and evaluation of the test results.In the guidelines, lung function results are evaluated as customary in terms of percent of predicted normal values, i.e. corrected for sex, age, height and, for some variables, also weight (exercise test) [1].In our opinion, the correction for age is inappropriate when estimating peri-operative risk.This is because expressing lung function results in percent of predicted normal values results in ignorance of the normal age-related decline in lung function and exercise capacity.The guidelines recommend a post-operative predicted FEV1 value of 30% predicted to be a high-risk threshold.30% pred normal FEV1 for a 70-yr-old male with a height of 178 cm is 0.9 L compared with 1.3 L for a male of the same height aged 25 yrs [2].Thus, according to the recommendations, the high-risk threshold regarding FEV1 is 0.9 L for a 70-yr-old patient but 1.3 L for the 25 yr old!There are of course similar consequences regarding DL,CO and exercise capacity.One of several possible ways to deal with this problem is to express results of lung function tests and exercise tests of adults as percent of predicted normal at age 25 yrs (% pred25yrs) irrespective of the actual age.In the example above regarding the 70-yr-old patient, the guideline recommended high-risk threshold of post-operative predicted 30% pred corresponds to 0.9 L, which is equivalent to a post-operative predicted value of ,20% pred25yrs.Thus, we suggest the high-risk threshold to be 20% pred25yrs for FEV1, DL,CO and exercise capacity.
Molecular Pathways: Transcription Factories and Chromosomal Translocations
Authors: Cameron S. Osborne
Journal: Clinical Cancer Research (2013)

Abstract The mammalian nucleus is a highly complex structure that carries out a diverse range of functions such as DNA replication, cell division, RNA processing, and nuclear export/import. Many of these activities occur at discrete subcompartments that intersect with specific regions of the genome. Over the past few decades, evidence has accumulated to suggest that RNA transcription also occurs in specialized sites, called transcription factories, that may influence how the genome is organized. There may be certain efficiency benefits to cluster transcriptional activity in this way. However, the clustering of genes at transcription factories may have consequences for genome stability, and increase the susceptibility to recurrent chromosomal translocations that lead to cancer. The relationships between genome organization, transcription, and chromosomal translocation formation will have important implications in understanding the causes of therapy-related cancers. Clin Cancer Res; 20(2); 296–300. ©2013 AACR.
Long-Term Clinical Outcome After Fractional Flow Reserve-Guided Percutaneous Coronary Intervention in Patients With Multivessel Disease
Authors: Alexandre Berger, Kees-Joost Botman, Philip A. MacCarthy, William Wijns, Jozef Bartunek, Guy R. Heyndrickx, Nico H.J. Pijls, Bernard De Bruyne
Journal: Journal of the American College of Cardiology (2005)
Long-term benefit of 1-year amiodarone treatment for persistent complex ventricular arrhythmias after myocardial infarction.
Authors: M E Pfisterer, W Kiowski, H Brunner, D Burckhardt, F Burkart
Journal: Circulation (1993)

BACKGROUND In the Basel Antiarrhythmic Study of Infarct Survival trial, low-dose amiodarone improved 1-year survival in patients with asymptomatic complex ventricular arrhythmias persisting 2 weeks after myocardial infarction. To assess whether this beneficial effect persisted despite discontinuation of amiodarone after 1 year, the long-term outcomes of all patients of the amiodarone-treated group (initially n = 98) and those of the control group (n = 114) were assessed. METHODS AND RESULTS After a mean follow-up of 72 (55-125) months, information on 96% of patients (203 of 212) was obtained regarding survival or cause of death. The probability of death after 84 months according to actuarial life-table analysis (Kaplan-Meier) was 30% for the amiodarone-treated patients and 45% for control patients. For the total follow-up, mortality remained significantly lower in the amiodarone group versus the control group regarding all deaths (p = 0.03) as well as cardiac death (p = 0.047). This mortality reduction was entirely due to the first-year amiodarone effect, since there was no significant mortality difference between groups when considering survival after discontinuation of amiodarone only. CONCLUSIONS These data suggest that the beneficial effect of amiodarone on survival in this high-risk group of patients persists for several years. In addition, the results stress the importance of early treatment after myocardial infarction, whereas the rate of sudden death and all cardiac death is low (1.6% and 4.1% per year, respectively) during late follow-up and therefore may not warrant further therapy.
Including Children and Adolescents With Schizophrenia in Medication-Free Research
Authors: Sanjiv Kumra, Claudia Briguglio, Marge Lenane, Laura Goldhar, Jeffrey Bedwell, Julia Venuchekov, Leslie K. Jacobsen, Judith L. Rapoport
Journal: American Journal of Psychiatry (1999)

There has been an increasing focus on the ethical issues raised by studies requiring the withdrawal of effective medication in schizophrenic adults. This article examines the risks and benefits of a medication-free period for pediatric patients with treatment-refractory schizophrenia who are participating in an ongoing study.Between April 1993 and March 1998, 31 children and adolescents were admitted with a diagnosis of treatment-resistant, childhood-onset schizophrenia. Parental consent was obtained so that patients could participate in a medication-free research period. Patients were evaluated at screening, at the end of a 4-week washout, at the completion of a 6- to 8-week atypical neuroleptic trial, and at a 2- to 4-year follow-up.At the completion of a 4-week drug-free period, seven patients (23%) were diagnosed with another disorder on the basis of data gained from the drug-free period and their lack of schizophrenic symptoms. Their revised diagnoses were posttraumatic stress disorder (N = 1), an atypical psychosis labeled "multidimensionally impaired" (N = 4), and personality disorder (N = 2). At follow-up, three of these patients remained free of neuroleptic therapy. For eight patients (26%), the washout was curtailed because of rapid and severe deterioration of their schizophrenic symptoms.For children and adolescents with treatment-refractory schizophrenia, a medication-free period can be conducted safely for at least 4 weeks for inpatients. Such trials are useful on clinical grounds and for providing homogeneous patient groups for research. This study also highlights the necessity of having access to hospitalization to observe children and adolescents with psychotic symptoms while medication free.