tbuckley/cabot-search huggingface dataset:
Pseudomonas aeruginosa bronchopulmonary infection in patients with AIDS, with emphasis on relapsing infection
Authors: P Domingo, A Ferre, MA Baraldes, J Ris, F Sanchez
Journal: European Respiratory Journal (1998)

The aim of this study was to delineate the clinical and therapeutic characteristics of Pseudomonas aeruginosa bronchopulmonary infection in acquired immunodeficiency syndrome (AIDS) patients. Eighteen AIDS patients had 39 episodes of P. aeruginosa bronchopulmonary infection. Their mean CD4 cell count was 0.012+/-0.011 cells x 10(9) x L(-1) and two episodes (5.1%) occurred in neutropenic patients. Ten patients (55.5%) had 21 outbreaks of pseudomonal infection. Relapses were more frequent in patients with chronic bronchitis (80 versus 0%, p=0.03) and in those who received initial oral antibiotic therapy (100 versus 55.6%, p=0.25). Three patients died, but death was directly related to pseudomonal infection in only one patient. In a case-control study, patients with bronchopulmonary P. aeruginosa infection had a survival comparable to patients in the control group. Immunoglobulin prophylaxis was administered to three patients with relapses, without success. The two patients who had P. aeruginosa eradicated were those who began triple antiretroviral therapy and had a CD4 cell increase &gt;0.150 cells x 10(9) x L(-1). Relapsing Pseudomonas aeruginosa bronchopulmonary infection affects patients with advanced human immunodeficiency virus infection, prior underlying lung disease, chronic bronchitis and initial oral antibiotic therapy. Immune reconstitution through triple antiretroviral therapy succeeded in eradicating Pseudomonas aeruginosa respiratory infection in two patients.
Fish Oils and Low-Molecular-Weight Heparin for the Reduction of Restenosis After Percutaneous Transluminal Coronary Angioplasty
Authors: John A. Cairns, John Gill, Brian Morton, Robin Roberts, Michael Gent, Jack Hirsh, Douglas Holder, Keith Finnie, Jean Franc¸ois Marquis, Salim Naqvi, Eric Cohen
Journal: Circulation (1996)

Background Percutaneous transluminal coronary angioplasty (PTCA) is complicated by restenosis within 6 months in &gt;40% of patients. Theoretical, animal experimental, and human epidemiological and clinical trial findings have suggested that fish oils (n-3) might reduce restenosis. Low-molecular-weight heparin (LMWH) has reduced cellular proliferation and restenosis in several experimental systems. Methods and Results We randomized 814 patients to fish oils (5.4 g n-3 fatty acids) or placebo a median of 6 days before PTCA and continued for 18 weeks. At the time of sheath removal, 653 patients with at least one successfully dilated lesion were randomized to LMWH (30 mg SC BID) or control for 6 weeks in a 2×2 factorial design. Follow-up with quantitative coronary angiography (QCA; target, 18 weeks) was interpretable on 96% of these patients. Restenosis rates per patient were for n-3, 46.5%; placebo, 44.7%; LMWH, 45.8%; and control, 45.4%. Restenosis rates per lesion were for n-3, 39.7%; placebo, 38.7%; LMWH, 38%; and control, 40.4%. At follow-up QCA, mean minimal lumen diameters were (mm) for n-3, 1.12; placebo, 1.10; LMWH, 1.12; and control, 1.10. Fifteen percent of patients permanently discontinued n-3/placebo before study completion, and 21% of patients discontinued LMWH early. There were no significant differences in the occurrences of ischemic events. Bleeding was more common with LMWH, usually was mild, and led to early discontinuation of study medication in only 0.9% of patients. Gastrointestinal side effects were more common in patients receiving n-3 than placebo. Conclusions There is no evidence for a clinically important reduction of PTCA restenosis in this trial by either n-3 or LMWH. Evaluation of the results for n-3 in the context of previously published data on the reduction of PTCA restenosis indicates that n-3 is not efficacious and that further trials are unwarranted.
Lipoprotein(a) Is an Independent Risk Factor for Peripheral Arterial Disease in Chinese Type 2 Diabetic Patients in Taiwan
Authors: Chin-Hsiao Tseng
Journal: Diabetes Care (2004)

OBJECTIVE—To examine the association between lipoprotein(a) [Lp(a)] and peripheral arterial disease (PAD) and determine the optimal cutoff in Chinese type 2 diabetic patients in Taiwan. RESEARCH DESIGN AND METHODS—Serum Lp(a) was determined in 557 type 2 diabetic patients (243 men and 314 women) recruited consecutively from a diabetes clinic at the National Taiwan University Hospital. Ankle-brachial index (ABI) &amp;lt;0.9 was diagnosed as PAD (n = 45) and &amp;lt;0.8 as severe PAD (n = 20). Potential confounders included age, sex, BMI, waist-to-hip ratio (WHR), diabetes duration, insulin usage, smoking, hypertension, systolic and diastolic blood pressure, fasting plasma glucose (FPG), total cholesterol, triglycerides, and HDL and LDL cholesterol. RESULTS—The distribution of Lp(a) was right skewed and no significant differences for sex, WHR, insulin usage, smoking, hypertension, and systolic and diastolic blood pressure were observed. In men, log[Lp(a)] was correlated positively with age, duration, and total and LDL cholesterol (borderline significant, P &amp;lt; 0.1) and negatively with BMI, triglycerides, and FPG (P &amp;lt; 0.1). In women, log[Lp(a)] was correlated positively with total and LDL cholesterol and negatively with triglycerides and BMI (P &amp;lt; 0.1). ABI was significantly correlated with log[Lp(a)], especially in men or in patients with PAD. The optimal cutoff determined by discriminant analysis was 13.3 mg/dl. Patients with Lp(a) above this value had a 2.7-fold higher risk of PAD after multivariate adjustment. Lp(a) also significantly increased from no PAD to mild and severe PAD (17.1 ± 14.4, 23.7 ± 20.3, and 36.9 ± 22.8 mg/dl, respectively, P &amp;lt; 0.001). CONCLUSIONS—Lp(a) is an independent risk factor for PAD in type 2 diabetic patients in Taiwan. The optimal cutoff is 13.3 mg/dl.
DURATION-1: Exenatide Once Weekly Produces Sustained Glycemic Control and Weight Loss Over 52 Weeks
Authors: John B. Buse, Daniel J. Drucker, Kristin L. Taylor, Terri Kim, Brandon Walsh, Hao Hu, Ken Wilhelm, Michael Trautmann, Larry Z. Shen, Lisa E. Porter
Journal: Diabetes Care (2010)

OBJECTIVE In the Diabetes Therapy Utilization: Researching Changes in A1C, Weight and Other Factors Through Intervention with Exenatide Once Weekly (DURATION-1) study, the safety and efficacy of 30 weeks of treatment with the glucagon-like peptide-1 receptor agonist exenatide once weekly (exenatide QW; 2 mg) was compared with exenatide BID in 295 patients with type 2 diabetes. We now report the safety and efficacy of exenatide QW in 1) patients who continued treatment for an additional 22 weeks (52 weeks total) and 2) patients who switched from exenatide BID to exenatide QW after 30 weeks. RESEARCH DESIGN AND METHODS In this randomized, multicenter, comparator-controlled, open-label trial, 258 patients entered the 22-week open-ended assessment phase (n = 128 QW-only; n = 130 BID→QW). A1C, fasting plasma glucose (FPG), body weight, blood pressure, fasting lipids, safety, and tolerability were assessed. RESULTS Patients continuing exenatide QW maintained A1C improvements through 52 weeks (least squares mean −2.0% [95% CI −2.1 to −1.8%]). Patients switching from exenatide BID to exenatide QW achieved further A1C improvements; both groups exhibited the same A1C reduction and mean A1C (6.6%) at week 52. At week 52, 71 and 54% of all patients achieved A1C &amp;lt;7.0% and ≤6.5%, respectively. In both treatment arms, FPG was reduced by &amp;gt;40 mg/dl, and body weight was reduced by &amp;gt;4 kg after 52 weeks. Nausea occurred less frequently in this assessment period and was predominantly mild. No major hypoglycemia was observed. CONCLUSION Exenatide QW elicited sustained improvements in glycemic control and body weight through 52 weeks of treatment. Patients switching to exenatide QW experienced further improvements in A1C and FPG, with sustained weight loss.
Insulin-Like Growth Factor (IGF)-I and IGF-II Serum Concentrations in Patients with Benign and Malignant Breast Lesions
Authors: Christian F. Singer, Maurice Mogg, Wolfgang Koestler, Margit Pacher, Erika Marton, Ernst Kubista, Martin Schreiber
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Insulin-like growth factors (IGFs) are potent mitogens for breast cancer cells in vitro, and elevated IGF-I serum levels are a risk factor for breast malignancies. This study evaluated IGF-I and IGF-II serum levels in healthy women and in patients with benign and malignant breast lesions and correlated them with tumor size. Experimental Design: Serum levels of the total and unbound fractions of IGF-I and IGF-II were analyzed in 65 patients with benign and malignant breast lesions and in 38 women without breast disease. ELISAs were used to detect serum IGF levels, with (total IGF) or without (free IGF) prior acid-ethanol extraction. Results: Total IGF-I serum concentrations were lower in healthy women than in breast cancer patients (P &amp;lt; 0.001) or patients with benign breast lesions (P = 0.010), but no differences were observed in free IGF-I levels. Conversely, healthy women had higher serum levels of free IGF-II than women with breast lesions (P = 0.003), and the free/total IGF-II ratio was significantly reduced in patients with breast disease (P = 0.001). Although IGF-I or IGF-II serum concentrations of breast cancer patients were similar to those of patients with benign lesions, the size of a malignant tumor was correlated to the ratio free/total IGF-II (P = 0.002). Conclusions: Malignant breast tumors cannot be distinguished from benign breast lesions by systemic IGF serum levels. However, women with breast lesions have decreased IGF-II concentrations, and free IGF-II levels are clearly correlated to the size of a breast cancer, indicating an involvement in tumor growth.
Harms associated with single unit perioperative transfusion: retrospective population based analysis
Authors: E. L. Whitlock, H. Kim, A. D. Auerbach
Journal: BMJ (2015)

<b>Objective</b> To determine whether perioperative transfusion of as little as one unit of packed red blood cells in the operating room or the day after surgery is associated with measurably increased odds for perioperative ischemic stroke and myocardial infarction. <b>Design</b> Retrospective cohort study of hospital administrative data. <b>Setting</b> 346 hospitals in the United States participating in the claims based Premier Perspective database from 1 January 2009 to 31 March 2012. <b>Participants</b> 1 583 819 adults who underwent non-cardiac, non-intracranial, non-vascular surgery and required a stay of at least one night in hospital and did not receive packed red blood cells on days two to seven after surgery. <b>Intervention</b> Transfusion of packed red blood cells on the day of surgery or one day after by exposure categories (none or one, two, three or four or more units). <b>Main outcome measures</b> The composite outcome of stroke/myocardial infarction was defined as ischemic stroke, ST elevation myocardial infarction, ventricular tachycardia, or ventricular fibrillation during index admission or as a primary diagnosis for readmission within 30 days. Ventricular tachycardia/ventricular fibrillation were included as a surrogate for myocardial infarction. <b>Results</b> 41 421 (2.6%) patients received at least one unit of packed red blood cells within 48 hours of surgery, and 8044 (0.51%) experienced the composite outcome of stroke/myocardial infarction. Patients who were transfused were older, more likely to be women, and had more comorbid disease. Hierarchical logistic regression adjusted for comorbidities and demographics with random effects by hospital showed that transfusion of as little as one unit was associated with an odds ratio of 2.33 (95% confidence interval 1.90 to 2.86) for perioperative stroke/myocardial infarction, and the odds of stroke/myocardial infarction markedly increased with transfusion of four or more units. Subgroup analysis limiting the cohort to one of several common surgical procedures, excluding those who received two or more units, or excluding who received transfusion on postoperative day one showed substantially similar results, as did a matched propensity score analysis. Two methods of modeling unmeasured confounders suggest an odds ratio of &gt;10 with imbalance of up to 47% between patients who did and did not receive transfusion would be required to invalidate our results. <b>Conclusions</b> A perioperative transfusion of one unit of packed red blood cells is associated with increased odds of perioperative ischemic stroke and/or myocardial infarction, even after adjustment for a wide range of factors in our data and despite extensive sensitivity analyses.
Objective measurement of compliance during oral appliance therapy for sleep-disordered breathing
Authors: Olivier M Vanderveken, Marijke Dieltjens, Kristien Wouters, Wilfried A De Backer, Paul H Van de Heyning, Marc J Braem
Journal: Thorax (2012)

Background Oral appliance (OA) therapy is increasingly prescribed as a non-continuous positive airway pressure treatment modality for sleep-disordered breathing (SDB).Although OA therapy is reported to be efficacious for the treatment of SDB, data on compliance remain limited to self-report.Methods In this 3-month prospective clinical trial, the main outcome was to assess the safety and feasibility of an objective measurement of compliance during OA therapy using an embedded microsensor thermometer with on-chip integrated readout electronics in 51 consecutive patients with an established diagnosis of SDB (AHI 18.0±11.9/h;age 47±10 y; BMI 26.6±4.0kg/m 2 ; men/women: 31/20).Patients were unaware of the purpose of the study.Results No microsensor-related adverse events were recorded.In addition, no problems were encountered during the readout of the compliance data.Out of 51 microsensors, one had a technical defect and was lost to follow-up.In this study, the overall objective mean rate of OA use was 6.6±1.3 h per day with a regular OA users' rate of 82% at the 3-month follow-up.Statistical analysis revealed no significant differences between objective and self-reported OA compliance data in this study.Measurement of the objective OA compliance allowed us to calculate the mean disease alleviation (MDA) as the product of objective compliance and therapeutic efficacy.MDA serves as a measure of the overall therapeutic effectiveness, and turned out to be 51.1%.Conclusions The results illustrate the safety and feasibility of objective measurement of OA compliance.The objective measurement of OA compliance allows for calculation of the MDA.
Long-Term Impact of Neonatal Breastfeeding on Childhood Adiposity and Fat Distribution Among Children Exposed to Diabetes In Utero
Authors: Tessa L. Crume, Lorraine Ogden, MaryBeth Maligie, Shelly Sheffield, Kimberly J. Bischoff, Robert McDuffie, Stephen Daniels, Richard F. Hamman, Jill M. Norris, Dana Dabelea
Journal: Diabetes Care (2011)

OBJECTIVE To evaluate whether breastfeeding attenuates increased childhood adiposity associated with exposure to diabetes in utero. RESEARCH DESIGN AND METHODS Retrospective cohort study of 89 children exposed to diabetes in utero and 379 unexposed youth with measured BMI, waist circumference, skinfolds, visceral (VAT) and subcutaneous (SAT) abdominal fat. A measure of breast milk–months was derived from maternal self-report and used to categorize breastfeeding status as low (&amp;lt;6) and adequate (≥6 breast milk–months). Multiple linear regression was used to model the relationship between exposure to diabetes in utero and offspring adiposity outcomes among youth stratified according to breastfeeding status. RESULTS Adequate (vs. low) breastfeeding status was associated with significantly lower BMI, waist circumference, SAT, and VAT at ages 6–13 years. Among youth in the low breastfeeding category, exposure to diabetes in utero was associated with a 1.7 kg/m2 higher BMI (P = 0.03), 5.8 cm higher waist circumference (P = 0.008), 6.1 cm2 higher VAT (P = 0.06), 44.6 cm2 higher SAT (P = 0.03), and 0.11 higher ratio of subscapular-to-triceps skinfold ratio (P = 0.008). Among those with adequate breastfeeding in infancy, the effect of prenatal exposure to diabetes on childhood adiposity outcomes was not significant. CONCLUSIONS Adequate breastfeeding protects against childhood adiposity and reduces the increased adiposity levels associated with exposure to diabetes in utero. These data provide support for mothers with diabetes during pregnancy to breastfeed their infants in order to reduce the risk of childhood obesity.
Expression of p53, Glutathione S -Transferase- , and Bcl-2 Proteins and Benefit From Adjuvant Radiotherapy in Breast Cancer
Authors: R. Silvestrini, S. Veneroni, E. Benini, M. G. Daidone, A. Luisi, M. Leutner, A. Maucione, R. Kenda, R. Zucali, U. Veronesi
Journal: JNCI Journal of the National Cancer Institute (1997)

In clinical breast cancer research, the utility of certain biomarkers as predictors of response to surgery, chemotherapy, or hormonal therapy has been studied intensively. Much less research has been done on the relevance of biologic predictors of response to radiotherapy, which represents an effective local-regional treatment for breast cancer.The utility of biomarkers involved in DNA damage repair (p53 protein), control of programmed cell death (p53 and Bcl-2 proteins), and cellular detoxification (glutathione S-transferase-pi [GST-pi] enzyme) in predicting local breast cancer recurrence was analyzed retrospectively in two cohorts of breast cancer patients. These patients had had no detectable metastases in the axillary lymph nodes (i.e., node-negative) or in distant sites and had had similar distributions of clinicopathologic and biologic prognostic features. They had been treated by conservative surgery alone (139 case patients) or by conservative surgery followed by adjuvant radiotherapy (496 case patients) during the period from 1984 through 1990.The expression of the p53, GST-pi, and Bcl-2 proteins in the specimens of primary breast tumor obtained from these patients was determined by use of immunohistochemistry; cell proliferation activity and levels of steroid receptors were determined by use of a [3H]thymidine-labeling index assay and the dextran-coated charcoal technique, respectively. The median time of follow-up of patients was 6 years. In the analyses of patient outcomes, only local failures that presented as first events were considered.After surgery alone, the risk of local recurrence at 6 years was higher for patients with tumors exhibiting elevated levels of p53 and GST-pi protein expression than for patients with low levels (hazard ratio [HR] = 3.1, 95% confidence interval [CI] = 1.3-7.7, two-sided P = .012; HR = 2.7, 95% CI = 1.1-6.4, two-sided P = .026, respectively). Weak or no observable expression of Bcl-2 protein was only suggestive of a higher frequency of local failures. Adjustment for patient age, tumor size, cell proliferation, and estrogen receptor status did not change these findings. Conversely, in the series of patients given conservative surgery followed by radiotherapy, there was no difference in local tumor recurrence between patients with tumors expressing or not expressing each of the three markers.Our study provides indirect evidence of a benefit from radiation therapy in preventing local breast cancer relapse, particularly among node-negative patients with tumors that express elevated levels of the p53 or GST-pi proteins or that express little or no Bcl-2 protein.
Comparative and functional genomics provide insights into the pathogenicity of dermatophytic fungi
Authors: Anke Burmester, Ekaterina Shelest, Gernot Glöckner, Christoph Heddergott, Susann Schindler, Peter Staib, Andrew Heidel, Marius Felder, Andreas Petzold, Karol Szafranski, Marc Feuermann, Ivo Pedruzzi, Steffen Priebe, Marco Groth, Robert Winkler, Wenjun Li, Olaf Kniemeyer, Volker Schroeckh, Christian Hertweck, Bernhard Hube, Theodore C White, Matthias Platzer, Reinhard Guthke, Joseph Heitman, Johannes Wöstemeyer, Peter F Zipfel, Michel Monod, Axel A Brakhage
Journal: Genome biology (2011)

Abstract Background Millions of humans and animals suffer from superficial infections caused by a group of highly specialized filamentous fungi, the dermatophytes, which exclusively infect keratinized host structures. To provide broad insights into the molecular basis of the pathogenicity-associated traits, we report the first genome sequences of two closely phylogenetically related dermatophytes, Arthroderma benhamiae and Trichophyton verrucosum , both of which induce highly inflammatory infections in humans. Results 97% of the 22.5 megabase genome sequences of A. benhamiae and T. verrucosum are unambiguously alignable and collinear. To unravel dermatophyte-specific virulence-associated traits, we compared sets of potentially pathogenicity-associated proteins, such as secreted proteases and enzymes involved in secondary metabolite production, with those of closely related onygenales ( Coccidioides species) and the mould Aspergillus fumigatus . The comparisons revealed expansion of several gene families in dermatophytes and disclosed the peculiarities of the dermatophyte secondary metabolite gene sets. Secretion of proteases and other hydrolytic enzymes by A. benhamiae was proven experimentally by a global secretome analysis during keratin degradation. Molecular insights into the interaction of A. benhamiae with human keratinocytes were obtained for the first time by global transcriptome profiling. Given that A. benhamiae is able to undergo mating, a detailed comparison of the genomes further unraveled the genetic basis of sexual reproduction in this species. Conclusions Our results enlighten the genetic basis of fundamental and putatively virulence-related traits of dermatophytes, advancing future research on these medically important pathogens.
Magnetic resonance imaging of brain in people at high risk of developing schizophrenia
Authors: Stephen M Lawrie, Heather Whalley, Julia N Kestelman, Suheib S Abukmeil, Majella Byrne, Ann Hodges, J Ewen Rimmington, Jonathan JK Best, David GC Owens, Eve C Johnstone
Journal: The Lancet (1999)
Connecting doctors, patients, and the evidence
Authors: B. Nash
Journal: BMJ (2003)

<h3>Abstract</h3> The clarification of genomic signatures left during evolutionary histories of crops is crucial for breeding varieties adapting to changing climate. Soybean, a leguminous crop, provides both plant oil and protein. Here, we analyzed genome sequences of 2,214 soybeans and proposed its evolutionary route, which includes four geographic paths, expansion of annual wild soybean (<i>Glycine soja</i> Sieb. &amp; Zucc.) from Southern China, domestication in Central China, expansion of landrace (<i>G. max</i> (L.) Merr.), and local breeding. We observed that local adaptation of the wild and cultivated soybeans was largely independent, and that genetic introgression was mostly derived from sympatric rather than allopatric wild populations during the range expansion of soybean landraces. Range expansion and breeding processes were accompanied with positive selection of flowering-time genes including <i>GmSPA3c</i> as validated by knock-out mutants. Our study shed lights on the evolutionary history of soybean and provides valuable genetic resources for future breeding. <h3>Teaser</h3> The expansion and selection history of soybean