tbuckley/cabot-search huggingface dataset:
Association of Biochemical B12 Deficiency With Metformin Therapy and Vitamin B12 Supplements
Authors: Lael Reinstatler, Yan Ping Qi, Rebecca S. Williamson, Joshua V. Garn, Godfrey P. Oakley
Journal: Diabetes Care (2011)

To describe the prevalence of biochemical B(12) deficiency in adults with type 2 diabetes taking metformin compared with those not taking metformin and those without diabetes, and explore whether this relationship is modified by vitamin B(12) supplements.Analysis of data on U.S. adults ≥50 years of age with (n = 1,621) or without type 2 diabetes (n = 6,867) from the National Health and Nutrition Examination Survey (NHANES), 1999-2006. Type 2 diabetes was defined as clinical diagnosis after age 30 without initiation of insulin therapy within 1 year. Those with diabetes were classified according to their current metformin use. Biochemical B(12) deficiency was defined as serum B(12) concentrations ≤148 pmol/L and borderline deficiency was defined as >148 to ≤221 pmol/L.Biochemical B(12) deficiency was present in 5.8% of those with diabetes using metformin compared with 2.4% of those not using metformin (P = 0.0026) and 3.3% of those without diabetes (P = 0.0002). Among those with diabetes, metformin use was associated with biochemical B(12) deficiency (adjusted odds ratio 2.92; 95% CI 1.26-6.78). Consumption of any supplement containing B(12) was not associated with a reduction in the prevalence of biochemical B(12) deficiency among those with diabetes, whereas consumption of any supplement containing B(12) was associated with a two-thirds reduction among those without diabetes.Metformin therapy is associated with a higher prevalence of biochemical B(12) deficiency. The amount of B(12) recommended by the Institute of Medicine (IOM) (2.4 μg/day) and the amount available in general multivitamins (6 μg) may not be enough to correct this deficiency among those with diabetes.
Insulin Sensitivity and Albuminuria: The RISC Study
Authors: Stefan Pilz, Femke Rutters, Giel Nijpels, Coen D.A. Stehouwer, Kurt Højlund, John J. Nolan, Beverley Balkau, Jacqueline M. Dekker
Journal: Diabetes Care (2014)

Accumulating evidence suggests an association between insulin sensitivity and albuminuria, which, even in the normal range, is a risk factor for cardiovascular diseases. We evaluated whether insulin sensitivity is associated with albuminuria in healthy subjects.We investigated 1,415 healthy, nondiabetic participants (mean age 43.9 ± 8.3 years; 54.3% women) from the RISC (Relationship between Insulin Sensitivity and Cardiovascular Disease) study, of whom 852 participated in a follow-up examination after 3 years. At baseline, insulin sensitivity was assessed by hyperinsulinemic-euglycemic clamps, expressed as the M/I value. Oral glucose tolerance test-based insulin sensitivity (OGIS), homeostasis model assessment of insulin resistance (HOMA-IR), and urinary albumin-to-creatinine ratio (UACR) were determined at baseline and follow-up.Microalbuminuria (UACR ≥30 mg/g) was present in fewer than 2% at either study visit. After multivariate adjustments, there was no cross-sectional association between UACR and any measure of insulin sensitivity. Neither OGIS nor HOMA-IR was significantly associated with follow-up UACR, but in a multivariate regression analysis, baseline M/I emerged as an independent predictor of UACR at follow-up (β-coefficient -0.14; P = 0.001).In healthy middle-aged adults, reduced insulin sensitivity, assessed by hyperinsulinemic-euglycemic clamp, is continuously associated with a greater risk of increasing albuminuria. This finding suggests that reduced insulin sensitivity either is simply related to or might causally contribute to the initial pathogenesis of albuminuria.
Effect of Terbutaline, a β<sub>2</sub>‐adrenergic Receptor Stimulating Compound, on Cutaneous Responses to Histamine, Allergen, Compound 48/80, and Trypsin
Authors: Reidar Grönneberg, Kjell Strandberg, ÖSten Hägermark
Journal: Allergy (1979)

The β‐adrenoceptor stimulating agent terbutaline (2 ng‐2 μg) injected intradermally in eight atopic subjects produced a dose‐dependent inhibition of the skin reactions induced by subsequently injected allergen. After injection of 0.5 μg terbutaline inhibition of the flare and weal responses was demonstrable throughout the observation period of 90 min. The flare response induced by histamine, the histamine liberator compound 48/80 and the proteolytic enzyme trypsin was not inhibited by terbutaline in the doses used, suggesting a selective action of terbutaline on the allergen‐induced response. The weal response elicited by histamine and compound 48/80 was slightly reduced by 2 ng terbutaline. It is suggested that pretreatment of me skin with terbutaline interferes with the ability of the cutaneous mast cells to respond to challenge with allergen and that terbutaline produces this effect in doses lower than those needed to counteract the permeability increasing effect of released mediator substances.
Philadelphia-Negative Classical Myeloproliferative Neoplasms: Critical Concepts and Management Recommendations From European LeukemiaNet
Authors: Tiziano Barbui, Giovanni Barosi, Gunnar Birgegard, Francisco Cervantes, Guido Finazzi, Martin Griesshammer, Claire Harrison, Hans Carl Hasselbalch, Rudiger Hehlmann, Ronald Hoffman, Jean-Jacques Kiladjian, Nicolaus Kröger, Ruben Mesa, Mary F. McMullin, Animesh Pardanani, Francesco Passamonti, Alessandro M. Vannucchi, Andreas Reiter, Richard T. Silver, Srdan Verstovsek, Ayalew Tefferi
Journal: Journal of Clinical Oncology (2011)

We present a review of critical concepts and produce recommendations on the management of Philadelphia-negative classical myeloproliferative neoplasms, including monitoring, response definition, first- and second-line therapy, and therapy for special issues. Key questions were selected according the criterion of clinical relevance. Statements were produced using a Delphi process, and two consensus conferences involving a panel of 21 experts appointed by the European LeukemiaNet (ELN) were convened. Patients with polycythemia vera (PV) and essential thrombocythemia (ET) should be defined as high risk if age is greater than 60 years or there is a history of previous thrombosis. Risk stratification in primary myelofibrosis (PMF) should start with the International Prognostic Scoring System (IPSS) for newly diagnosed patients and dynamic IPSS for patients being seen during their disease course, with the addition of cytogenetics evaluation and transfusion status. High-risk patients with PV should be managed with phlebotomy, low-dose aspirin, and cytoreduction, with either hydroxyurea or interferon at any age. High-risk patients with ET should be managed with cytoreduction, using hydroxyurea at any age. Monitoring response in PV and ET should use the ELN clinicohematologic criteria. Corticosteroids, androgens, erythropoiesis-stimulating agents, and immunomodulators are recommended to treat anemia of PMF, whereas hydroxyurea is the first-line treatment of PMF-associated splenomegaly. Indications for splenectomy include symptomatic portal hypertension, drug-refractory painful splenomegaly, and frequent RBC transfusions. The risk of allogeneic stem-cell transplantation–related complications is justified in transplantation-eligible patients whose median survival time is expected to be less than 5 years.
Adalimumab: long-term safety in 23 458 patients from global clinical trials in rheumatoid arthritis, juvenile idiopathic arthritis, ankylosing spondylitis, psoriatic arthritis, psoriasis and Crohn's disease
Authors: Gerd R Burmester, Remo Panaccione, Kenneth B Gordon, Melissa J McIlraith, Ana P M Lacerda
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Background</h3> As long-term treatment with antitumour necrosis factor (TNF) drugs becomes accepted practice, the risk assessment requires an understanding of anti-TNF long-term safety. Registry safety data in rheumatoid arthritis (RA) are available, but these patients may not be monitored as closely as patients in a clinical trial. Cross-indication safety reviews of available anti-TNF agents are limited. <h3>Objective</h3> To analyse the long-term safety of adalimumab treatment. <h3>Methods</h3> This analysis included 23 458 patients exposed to adalimumab in 71 global clinical trials in RA, juvenile idiopathic arthritis, ankylosing spondylitis (AS), psoriatic arthritis, psoriasis (Ps) and Crohn9s disease (CD). Events per 100 patient-years were calculated using events reported after the first dose through 70 days after the last dose. Standardised incidence rates for malignancies were calculated using a National Cancer Institute database. Standardised death rates were calculated using WHO data. <h3>Results</h3> The most frequently reported serious adverse events across indications were infections with greatest incidence in RA and CD trials. Overall malignancy rates for adalimumab-treated patients were as expected for the general population; the incidence of lymphoma was increased in patients with RA, but within the range expected in RA without anti-TNF therapy; non-melanoma skin cancer incidence was raised in RA, Ps and CD. In all indications, death rates were lower than, or equivalent to, those expected in the general population. <h3>Conclusions</h3> Analysis of adverse events of interest through nearly 12 years of adalimumab exposure in clinical trials across indications demonstrated individual differences in rates by disease populations, no new safety signals and a safety profile consistent with known information about the anti-TNF class.
New contributions in the determination of volatile organic compounds (VOC) in lung cancer (LC)
Authors: Javier Jareño, Mª Angeles Muñoz, Gema Rodríguez, Concepciόn Civera, Antonio Aguilar, José Άngel Maldonado, Belén Carrillo, Carlos Gutiérrez, Maria Vicenta García, Beatriz Morales, José Luis Άlvarez-Sala, Luis Callol
Journal: European Respiratory Journal (2011)

Introduction: Determination of VOC present in exhaled breath (EB) may be useful as a noninvasive diagnostic technique in LC.

Objective: To analyze the presence of VOC in the EB in two groups of subject: LC Group and Control Group.

Methods: Descriptive, observational study. LC Group: 29 patients with LC. Control Group: 40 healthy volunteers. (All accepted Informed consent). Breath samples were collected at lung residual functional capacity, with simultaneous sampling of ambient air using BioVOC devices. Analytical technique: Thermal desorption (Markes Int.)-gas chromatography (7890A)-mass spectrometry (5975C-Agilent Tech). VOC analyzed, see table 2. Compounds identified by means of retention time + mass spectrum. Chromatographic column: DB1: 30mx0.25mmx1um (Agilent Tech).

Results: 

![Figure][1] 



Conclussions: 1.The presence of VOC (2butanone, Hexanal, Heptanal, Nonanal, Propanoic Acid, nonanoic Acid, Hexane and Tetradecane) exhibits significative differences between groups. 2. Quantification of VOC is extremely difficult because of the great amount of interfering compounds and the low concentrations found. 3.Clinical application of VOC as a noninvasive diagnostic technique in LC is not possible yet due to lack of standardization of methodology.

Acknowledge to Javier Martin from Agilent Tech. for his collaboration.

This work has been financed by FIS PI07/1116; Neumomadrid 2008 and SEPAR 2010.

 [1]: pending:yes
Update on Myocardial Bridging
Authors: Stefan Möhlenkamp, Waldemar Hort, Junbo Ge, Raimund Erbel
Journal: Circulation (2002)

uscle overlying the intramyocardial segment of an epicardial coronary artery, first mentioned by Reyman 1 in 1737, is termed a myocardial bridge, and the artery coursing within the myocardium is called a tunneled artery (Figure 1).It is characterized by systolic compression of the tunneled segment, which remains clinically silent in the vast majority of cases.][4][5] New imaging techniques have led to improved identification and functional quantitation of myocardial bridging in vivo, which is crucial for establishing a link between systolic compression and the clinical presentation, and hence for commencing appropriate therapy.In the present article, we summarize clinically relevant aspects of myocardial bridging with an emphasis on morphological and hemodynamic alterations and their representation in imaging techniques. PrevalenceThe prevalence varies substantially among studies with a much higher rate at autopsy versus angiography (Table ). 2,4 -28Variation at autopsy may in part be attributable to the care taken at preparation and the selection of hearts.Pola ´c ˇek, who included myocardial loops, reports the highest rate with bridges or loops in 86% of cases. 29On average, myocardial bridges are present in about one third of adults.The rate of angiographic bridging is Ͻ5%, attributable to thin bridges causing little compression.In subjects with angiographically normal coronary arteries, the use of provocation tests may enhance systolic myocardial compression and thereby reveal myocardial bridges in Յ40% of cases. 26,30 high prevalence has also been reported in heart transplant recipients 23 and in patients with hypertrophic obstructive cardiomyopathy (HOCM). 31In the latter, more rigorous contraction may unmask otherwise undetectable bridges.Myocardial bridging may be found at multiple sites in HOCM, 32 but also in patients without. 33De novo, previously nonexistent myocardial bridging has been suggested for both transplanted hearts 34 and HOCM, 35 but conclusive proof is lacking. 36 Comparative AnatomyAn epicardial course of coronary arteries is not obligatory in mammals.In rodents and lagomorpha, the major vessels are embedded in myocardium beneath the epicardial surface (Type I). 5,29Animals with a predominantly epicardial course of coronary arteries (Type II) include small ruminants, carnivores, and primates. 29,37Whereas the major coronary arteries in the gorilla form an epicardial network, they tend to take a mural course in the chimpanzee. 36In goats and sheep, bridges are more frequent than in humans. 8They can also be observed in canines, felines, and seals. 37In some mammals they are missing or extremely rare, such as in horses and pigs (Type III). 29Myocardial bridges are congenital in origin 38 -40 and likely reflect an evolutionary remnant in the genetic code.
Girl who had surgery to correct bronchial atresia in utero is healthy
Authors: A. Garcia Rada
Journal: BMJ (2012)

A multidisciplinary team of fetal medicine specialists and paediatric surgeons from two hospitals in Spain have carried out what is believed to be the first intrauterine surgical correction of a bronchial atresia.

The patient was a baby girl with a congenital total obstruction of the intermediate bronchus of the right lung that was endangering her life, the doctors explained in a press conference in Barcelona on 12 March.

Weighing just 800 g, she underwent the operation at 26 weeks of gestational age at the Sant Joan de Deu Hospital in Esplugues de Llobregat, Barcelona. The operation was carried out by …
IFN-γ mediates CD4+ T-cell loss and impairs secondary antitumor responses after successful initial immunotherapy
Authors: Vanessa Berner, Haiyan Liu, Qing Zhou, Kory L Alderson, Kai Sun, Jonathan M Weiss, Timothy C Back, Dan L Longo, Bruce R Blazar, Robert H Wiltrout, Lisbeth A Welniak, Doug Redelman, William J Murphy
Journal: Nature Medicine (2007)
Phase I and pharmacologic study of the combination paclitaxel and carboplatin as first-line chemotherapy in stage III and IV ovarian cancer.
Authors: M T Huizing, L J van Warmerdam, H Rosing, M C Schaefers, A Lai, T J Helmerhorst, C H Veenhof, M J Birkhofer, S Rodenhuis, J H Beijnen, W W ten Bokkel Huinink
Journal: Journal of Clinical Oncology (1997)

To determine the maximum-tolerated dose for the combination paclitaxel and carboplatin administered every 4 weeks and to gain more insight into the pharmacokinetics and pharmacodynamics of this combination in previously untreated ovarian cancer patients.Thirty-five chemotherapy-naive patients with suboptimally debulked stage III (tumor masses > 3 cm) and stage IV ovarian cancer were entered onto this phase I trial in which paclitaxel was administered as a 3-hour intravenous (IV) infusion at dosages of 125 to 225 mg/m2 immediately followed by carboplatin over 30 minutes at dosages of 300 to 600 mg/m2. A total of six courses was planned, followed by a second-look laparoscopy/laparotomy. Patients with a response and/or minimal residual disease at second-look laparoscopy received three additional courses. Twenty-six patients participated in the pharmacokinetic part of the study.The most important hematologic toxicity encountered was neutropenia. Neutropenia was more pronounced for the higher dose levels (DLs) and was cumulative. Thrombocytopenia was mild in the first eight DLs, but increased during the treatment courses. Nonhematologic toxicities consisted mainly of vomiting, neuropathy, fatigue, rash, pruritus, myalgia, and arthralgia. Dose-limiting toxicities (DLTs) in this trial were neutropenic fever, thrombocytopenia that required platelet transfusions, and cumulative neuropathy. Of 33 patients assessable for response, 26 major responders (78%, 20 complete response [CR] and six partial response [PR]) were documented. The maximal concentration (Cmax) of paclitaxel and the area under the concentration-time curve (AUC) were not different from the historical data for paclitaxel as a single agent. Retrospective analysis using a modified Calvert formula showed that the measured carboplatin AUCs in plasma ultrafiltrate (pUF) were 30% +/- 3.4% less than the calculated carboplatin AUC. Neutropenia was more pronounced than could be expected on the basis of the historical times above a threshold concentration greater than 0.1 mumol/L (T > or = 0.1 mumol/L) or 0.05 mumol/L (T > or = 0.05 mumol/L), and thrombocytopenia was less than could be expected from historical sigmoidal Emax models.The combination of paclitaxel 200 mg/ m2 and carboplatin 550 mg/m2 every 4 weeks is a well-tolerated treatment modality. The paclitaxel-carboplatin combination is highly active in stage III (bulky) and stage IV ovarian cancer. No indications for a pharmacokinetic drug-drug interaction between carboplatin and paclitaxel were found.
Thunderstorm outflows preceding epidemics of asthma during spring and summer
Authors: Guy Marks, John Colquhoun, Seaham Girgis, Hjelmroos Koski, Andrew Treloar, Peter Hansen, Sara Downs, Nicholas Car
Journal: Thorax (2001)

Background-A study was undertaken to assess the importance of thunderstorms as a cause of epidemics of asthma exacerbations and to investigate the underlying mechanism.Methods-A case control study was performed in six towns in south eastern Australia.Epidemic case days (n = 48) and a random sample of control days (n = 191) were identified by reference to the diVerence between the observed and expected number of emergency department attendances for asthma.The occurrence of thunderstorms, their associated outflows and cold fronts were ascertained, blind to case status, for each of these days.In addition, the relation of hourly pollen counts to automatic weather station data was examined in detail for the period around one severe epidemic of asthma exacerbations.The main outcome measure was the number of epidemics of asthma exacerbations.Results-Thunderstorm outflows were detected on 33% of epidemic days and only 3% of control days (odds ratio 15.0, 95% confidence interval 6.0 to 37.6).The association was strongest in late spring and summer.Detailed examination of one severe epidemic showed that its onset coincided with the arrival of the thunderstorm outflow and a 4-12 fold increase in the ambient concentration of grass pollen grains.Conclusions-These findings are consistent with the hypothesis that some epidemics of exacerbations of asthma are caused by high concentrations of allergenic particles produced by an outflow of colder air, associated with the downdraught from a thunderstorm, sweeping up pollen grains and particles and then concentrating them in a shallow band of air at ground level.This is a common cause of exacerbations of asthma during the pollen season.
The effect of neoadjuvant chemoradiotherapy on airway colonization and post operative respiratory complications in the patients undergoing esophagectomy for esophageal cancer
Authors: Reza Bagheri, Mohammad Taghi Rajabi
Journal: European Respiratory Journal (2011)

Background:  Different treatments are performed for esophageal cancer, but surgery is still the base of treatment. Respiratory complication is the important postoperative complications of esophageal cancer.   Methods:  In this study 40 patients who were candidates for surgery of esophageal cancer were placed into two groups of with or without neoadjuvant therapy. Before surgery, they underwent bronchoscopy and bronchoalveolar lavage. The samples were analyzed for airway colonization and then the patients underwent the surgery and were postoperatively evaluated in respiratory complications and the effects of preoperative neoadjuvant therapy.   Results:  M/F=23/17 and mean age was 61 years. 22 cases had cancer in the middle and 18 in the lower part of the esophagus. 25 cases had SCC and 15 had ACC. In evaluation, no organism was found in 9 cases (22.5%) and positive cases of microbial culture was found in 31 cases (77.5%). Significant relation was observed between airway positive microbial colonization and neoadjuvant therapy but no significant relation was found between neoadjuvant therapy and major respiratory complications such as pneumonia, ARDS. There was significant relation between difficult weaning and airway colonization, but no significant relation was found between length of hospitalization in ICU and receiving neoadjuvant therapy. Two deaths were reported due to myocardial infarction in the postoperative days.There was no death due to respiratory complications.   Conclusion:  Neoadjuvant therapy can used safle and it does not cause postoperative major pulmonary complications and related mortality.
Tobacco smoke exposure and multiplexed immunoglobulin E sensitization in children: a population‐based study
Authors: T.‐C. Yao, S.‐W. Chang, M.‐C. Hua, S.‐L. Liao, M.‐H. Tsai, S.‐H. Lai, Y.‐L. Tseng, K.‐W. Yeh, H.‐J. Tsai, J.‐L. Huang
Journal: Allergy (2015)

Although there is evidence that exposure to tobacco smoke is harmful to children's respiratory health, the effects of tobacco smoke exposure on the regulation of immunoglobulin E (IgE)-mediated immune responses to specific allergens remain unclear. This study aimed to investigate the relationship between objectively assessed tobacco smoke exposure and specific IgE profiles for a broad spectrum of allergens in a population setting.Children aged 5-18 years (N = 1315) were assessed using serum cotinine measurement and microarray-based multiplexed detection of specific IgE against 40 allergens.Serum cotinine levels were positively associated with sensitization to foods (adjusted odds ratio [AOR] = 4.95; 95% CI: 1.59-15.34), cockroaches (AOR = 3.77; 95% CI: 1.49-9.51), and pollen (AOR = 2.84; 95% CI: 1.20-6.73) while the association was borderline significant for animals (AOR = 2.53; 95% CI: 0.92-6.93). No associations were found for sensitization against mites, mold, and latex. When considering the degree of allergic sensitization, serum cotinine levels were positively correlated to the number of sensitization to cockroaches (P = 0.004), pollen (P = 0.006), and foods (P < 0.001), with statistically significant positive dose-response relationships (all P < 0.01). Similar results were observed when summing up specific IgE concentrations for the aforementioned allergen categories.The association between tobacco smoke exposure and IgE sensitization to environmental allergens varies for different allergens among children. This study demonstrates that elevated serum cotinine levels are significantly associated with IgE sensitization to cockroaches, grass pollen, and certain foods, with potential dose-dependent relationships.