bluuebunny/crossref_metadata_2025_split huggingface dataset:
A population-based cytogenetic study of adults with acute lymphoblastic leukemia
Authors: Moorman Anthony V. , Chilton Lucy , Wilkinson Jennifer , Ensor Hannah M. , Bown Nick , Proctor Stephen J. 
Published: November 2009

AbstractChromosomal abnormalities are increasingly used to risk stratify adults with acute lymphoblastic leukemia. Published data describing the age-specific incidence of chromosomal abnormalities and their prognostic relevance are largely derived from clinical trials. Trials frequently have age restrictions and low recruitment rates. Thus we investigated these factors in a population-based cohort of 349 patients diagnosed during the course of 19 years in the northern part of England. The incidence of most chromosomal abnormalities varied significantly with age. The incidence of t(9;22)(q34;q11) increased in each successive decade, up to 24% among 40- to 49-year-old subjects. Thereafter the incidence reached a plateau. t(4;11)(q21;q23) and t(1;19)(q23;p13) were a rare occurrence among patients older than 60 years of age. In contrast, the frequency of t(8;14)(q24;q32) and t(14;18)(q32;q21) increased with age. High hyperdiploidy occurred in 13% of patients younger than 20 years of age but in only 5% of older patients. The incidence of low hypodiploidy/near-triploidy and complex karyotype increased with age from 4% (15-29 years) to 16% (≥ 60 years). Overall survival varied significantly by age and cytogenetics. Older patients and those with t(9;22), t(4;11), low hypodiploidy/near-triploidy, or complex karyotype had a significantly inferior outcome. These population-based results demonstrate the cytogenetic heterogeneity of adult acute lymphoblastic leukemia. These data will inform the delivery of routine clinical services and the design of new age-focused clinical trials.
Differential genome-wide array–based methylation profiles in prognostic subsets of chronic lymphocytic leukemia
Authors: Kanduri Meena , Cahill Nicola , Göransson Hanna , Enström Camilla , Ryan Fergus , Isaksson Anders , Rosenquist Richard 
Published: November 2009

AbstractGlobal hypomethylation and regional hypermethylation are well-known epigenetic features of cancer; however, in chronic lymphocytic leukemia (CLL), studies on genome-wide epigenetic modifications are limited. Here, we analyzed the global methylation profiles in CLL, by applying high-resolution methylation microarrays (27 578 CpG sites) to 23 CLL samples, belonging to the immunoglobulin heavy-chain variable (IGHV) mutated (favorable) and IGHV unmutated/IGHV3-21 (poor-prognostic) subsets. Overall, results demonstrated significant differences in methylation patterns between these subgroups. Specifically, in IGHV unmutated CLL, we identified methylation of 7 known or candidate tumor suppressor genes (eg, VHL, ABI3, and IGSF4) as well as 8 unmethylated genes involved in cell proliferation and tumor progression (eg, ADORA3 and PRF1 enhancing the nuclear factor-κB and mitogen-activated protein kinase pathways, respectively). In contrast, these latter genes were silenced by methylation in IGHV mutated patients. The array data were validated for selected genes using methylation-specific polymerase chain reaction, quantitative reverse transcriptase–polymerase chain reaction, and bisulfite sequencing. Finally, the significance of DNA methylation in regulating gene promoters was shown by reinducing 4 methylated tumor suppressor genes (eg, VHL and ABI3) in IGHV unmutated samples using the methyl-inhibitor 5-aza-2′-deoxycytidine. Taken together, our data for the first time reveal differences in global methylation profiles between prognostic subsets of CLL, which may unfold epigenetic silencing mechanisms involved in CLL pathogenesis.
Endothelin-1 receptor antagonists prevent the development of pulmonary emphysema in rats
Authors: Chen Y. , Hanaoka M. , Droma Y. , Chen P. , Voelkel N. F. , Kubo K. 
Published: November 2009

We hypothesised that endothelin (ET)-1 plays an important role in the pathogenesis of emphysema. We attempted to apply ET-1 receptor antagonists to demonstrate and further elucidate the molecular pathogenesis pathways through which ET-1 may cause emphysematous changes.Sprague-Dawley rats were divided into four groups: control, cigarette smoke extract (CSE), CSE+BQ-123 (a selective endothelin receptor type A (ETA) antagonist) and CSE+bosentan (a mixed ETA/ETBreceptor antagonist). The CSE was injected intraperitoneally once a week for 3 weeks, and BQ-123 or bosentan was administered daily for the same duration. The expression of ETAreceptor, apoptosis index, caspase-3 activity, matrix metalloproteinase (MMP)-2 and MMP-9 activity, and tumour necrosis factor (TNF)-α and interleukin (IL)-1β concentrations were measured in the lung tissue. The ET-1 levels and antioxidant activity were measured in the serum.Both BQ-123 and bosentan prevented the development of CSE-induced emphysema, blocked the expression of ETAreceptor, inhibited pulmonary apoptosis, inactivated MMP-2 and MMP-9 activities in the lung tissues, reduced the concentrations of inflammatory cytokines TNF-α and IL-1β, and improved the biological antioxidant activity in the serum.Emphysema development is suppressed by ET-1 receptor antagonists. ET-1 may cause emphysematous changes through molecular pathogenesis pathways involving apoptosis, proteinase and antiproteinase imbalance, inflammation and oxidative stress.
Glutathione peroxidase-2 protects from allergen-induced airway inflammation in mice
Authors: Dittrich A. M. , Meyer H-A. , Krokowski M. , Quarcoo D. , Ahrens B. , Kube S. M. , Witzenrath M. , Esworthy R. S. , Chu F-F. , Hamelmann E. 
Published: November 2009

The aim of the present study was to identify and validate the biological significance of new genes/proteins involved in the development of allergic airway disease in a murine asthma model.Gene microarrays were used to identify genes with at least a two-fold increase in gene expression in lungs of two separate mouse strains with high and low allergic susceptibility. Validation of mRNA data was obtained by western blotting and immunohistochemistry, followed by functional analysis of one of the identified genes in mice with targeted disruption of specific gene expression.Expression of two antioxidant enzymes, glutathione peroxidase-2 (GPX2) and glutathioneS-transferase omega (GSTO) 1-1 was increased in both mouse strains after induction of allergic airway disease and localised in lung epithelial cells. Mice with targeted disruption of theGpx-2gene showed significantly enhanced airway inflammation compared to sensitised and challenged wild-type mice.Our data indicate that genes encoding the antioxidants GPX2 andGSTO 1-1are common inflammatory genes expressed upon induction of allergic airway inflammation, and independently of allergic susceptibility. Furthermore, we provide evidence to illustrate the importance of a single antioxidant enzyme, GPX2, in protection from allergen-induced disease.
Variability in the prevalence of premenstrual asthma
Authors: Pereira Vega A. , Sánchez Ramos J. L. , Maldonado Pérez J. A. , Álvarez Gutierrez F. J. , Ignacio García J. M. , Vázquez Oliva R. , Romero Palacios P. , Bravo Nieto J. M. , Sánchez Rodríguez I. , Gil Muñoz F. 
Published: November 2009

Our aim is to analyse the differences in the prevalence of premenstrual asthma (PMA) according to a set of criteria, the relationship between them and the influence of asthma severity.The answer “Yes” to “Does your asthma get worse before menstruation?” was considered subjective PMA. A daily respiratory symptoms register of fertile asthmatic females was taken during two consecutive menstrual cycles. For the semi-objective diagnosis, an exacerbation of ≥20% was required in the symptoms register. Objective diagnosis was a premenstrual worsening of ≥20% of peak flow.We selected 103 patients. Subjective premenstrual deterioration was perceived in 43.7%. The semi-objective deterioration of symptoms in the first cycle occurred in 44.7%, and in 22.3% in both cycles. A total of 54.3% of females with semi-objective criteria in the first cycle perceived a subjective deterioration of symptoms,versus35.1% of those without semi-objective criteria (p = 0.05). PMA was present at all levels of asthma severity, with no clear link to the degree of severity.The detection of PMA prevalence, the subjective perception of this deterioration and its presence at all levels of asthma severity lead us to urge research into possible premenstrual deterioration in all fertile asthmatic females.
Prognostic factors of acute heart failure in patients with pulmonary arterial hypertension
Authors: Sztrymf B. , Souza R. , Bertoletti L. , Jaïs X. , Sitbon O. , Price L. C. , Simonneau G. , Humbert M. 
Published: November 2009

Acute right ventricular failure in the setting of pulmonary arterial hypertension (PAH) often requires hospitalisation in intensive care units (ICU) to manage the subsequent low cardiac output and its consequences. There are very few data on these acute events.We recorded demographic, clinical and biological data and therapy in consecutive patients suffering from acute right heart failure requiring catecholamine treatment in the ICU of the French referral centre for pulmonary hypertension. These variables were analysed according to the survival status in ICU.46 patients were included, the mean age was 50.3 yrs. ICU mortality was 41%. We found no difference in terms of demographics, clinical data, last haemodynamic measurements at admission. Systemic arterial pressure was significantly lower in the subgroup of patients whose clinical course was fatal. Plasma brain natriuretic peptide (BNP), C-reactive protein (CRP), serum sodium and creatinine at admission correlated with survival. Demonstration of an infection during the ICU stay was associated with a worse prognosis.These preliminary results underline the importance of some simple clinical and biological parameters in the prognostic evaluation of acute heart failure in the setting of PAH. Whether these parameters can guide therapy needs to be further investigated.
Negative impacts of unreported COPD exacerbations on health-related quality of life at 1 year
Authors: Xu W. , Collet J-P. , Shapiro S. , Lin Y. , Yang T. , Wang C. , Bourbeau J. 
Published: November 2009

Unreported chronic obstructive pulmonary disease (COPD) exacerbations are common, but their intermediate-to-long-term impacts on health-related quality of life (HRQoL) are unknown. The aim of the present study was to examine the impact of unreported exacerbations on HRQoL at 1 yr.A multicentric prospective cohort study in 491 COPD patients was conducted in China. HRQoL was measured using the St George's Respiratory Questionnaire (SGRQ). Other measurements included sociodemographic, clinical, psychosocial and treatment profiles. Patients were monitored monthly for 12 months to document exacerbations (at least one symptom worsening for ≥48 h). Patients were categorised into six groups: no exacerbation, one unreported exacerbation only, more than one unreported exacerbation only, one reported exacerbation only, more than one reported exacerbation only, and both unreported and reported exacerbations. Generalised estimating equations were used to estimate the adjusted associations between exacerbations and HRQoL change.A total of 466 unreported and 410 reported exacerbations were recorded. Compared with patients with no exacerbations, the change in SGRQ total score was similar amongst patients with one unreported exacerbation (adjusted mean change 1.22 points (95% CI -4.05–6.48)), but significantly worse among patients with more than one unreported exacerbation (4.61 (95% CI 0.09–9.13)).Development and evaluation of self-management programmes emphasising early recognition of exacerbations and consequent action appear to be warranted.
Development and validation of the Capacity of Daily Living during the Morning questionnaire and the Global Chest Symptoms Questionnaire in COPD
Authors: Partridge M.R. , Miravitlles M. , Ståhl E. , Karlsson N. , Svensson K. , Welte T. 
Published: November 2009

This report concerns the development and validation of two patient-reported outcomes questionnaires developed to assess chronic obstructive pulmonary disease (COPD) patients’ ability to perform morning activities and to evaluate their morning symptoms.Based on interviews with COPD patients, the Capacity of Daily Living during the Morning (CDLM) questionnaire and the Global Chest Symptoms Questionnaire (GCSQ) were developed, linguistically validated and incorporated into two multicentre, randomised trials involving a total of 1,100 COPD patients; those trials were registered at ClinicalTrials.gov (NCT00496470andNCT00542880) . Data from these trials were used to determine the reliability, validity and responsiveness of the questionnaires and to derive estimates of minimal important differences (MIDs).Both questionnaires displayed good-to-high reliability (Cronbach’s α 0.75–0.93). Analysis of convergent validity showed that CDLM and GCSQ scores correlated significantly (p<0.001) with symptoms, health-related quality of life (HRQoL) and use of rescue medication. In both trials, CDLM and GCSQ scores discriminated between patients with different levels of HRQoL, as assessed by the St George's Respiratory Questionnaire for COPD patients (SGRQ-C), but not with disease severity, as assessed by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria. A significant improvement in CDLM and GCSQ scores occurred in response to treatment. Estimations of MID scores, corresponding to an SGRQ-C MID of 4, were 0.20 for the CDLM questionnaire and 0.15 for the GCSQ.Both the CDLM questionnaire and the GCSQ are easy-to-use, reliable, responsive, self-administered questionnaires that report on patients' symptoms and ability to perform morning activities.
Prevalence of sarcoidosis in Switzerland is associated with environmental factors
Authors: Deubelbeiss U. , Gemperli A. , Schindler C. , Baty F. , Brutsche M. H. 
Published: November 2009

The current study aimed to investigate incidence, prevalence and regional distribution of sarcoidosis in Switzerland with respect to environmental exposures.All sarcoidosis patients hospitalised between 2002 and 2005 were identified from the Swiss hospital statistics from the Swiss Federal Office for Statistics (Neuchâtel, Switzerland). Regional exposure characteristics included the regional distribution of different industrial sectors, agriculture and air quality. Co-inertia analysis, as well as a generalised linear model, was applied.The prevalence of “ever-in-life” diagnosed sarcoidosis, currently active sarcoidosis and sarcoidosis requiring hospitalisation was 121 (95% CI 93–149), 44 (95% CI 34–54) and 16 (95% CI 10–22) per 100,000 inhabitants, respectively. The mean annual incidence of sarcoidosis was 7 (95% CI 5–11) per 100,000 inhabitants. The regional workforce in the metal industry, water supply, air transport factories and the area of potato production, artificial meadows (grassland) and bread grains were positively associated with the frequency of sarcoidosis.The prevalence of sarcoidosis was higher than assumed based on former international estimates. Higher frequency was found in regions with metal industry and intense agriculture, especially production of potatoes, bread grains and artificial meadows.
Performance of optimized McRAPD in identification of 9 yeast species frequently isolated from patient samples: potential for automation
Authors: Trtkova Jitka , Pavlicek Petr , Ruskova Lenka , Hamal Petr , Koukalova Dagmar , Raclavsky Vladislav 
Published: November 2009

Abstract

Background
Rapid, easy, economical and accurate species identification of yeasts isolated from clinical samples remains an important challenge for routine microbiological laboratories, because susceptibility to antifungal agents, probability to develop resistance and ability to cause disease vary in different species. To overcome the drawbacks of the currently available techniques we have recently proposed an innovative approach to yeast species identification based on RAPD genotyping and termed McRAPD (Melting curve of RAPD). Here we have evaluated its performance on a broader spectrum of clinically relevant yeast species and also examined the potential of automated and semi-automated interpretation of McRAPD data for yeast species identification.

Results
A simple fully automated algorithm based on normalized melting data identified 80% of the isolates correctly. When this algorithm was supplemented by semi-automated matching of decisive peaks in first derivative plots, 87% of the isolates were identified correctly. However, a computer-aided visual matching of derivative plots showed the best performance with average 98.3% of the accurately identified isolates, almost matching the 99.4% performance of traditional RAPD fingerprinting.

Conclusion
Since McRAPD technique omits gel electrophoresis and can be performed in a rapid, economical and convenient way, we believe that it can find its place in routine identification of medically important yeasts in advanced diagnostic laboratories that are able to adopt this technique. It can also serve as a broad-range high-throughput technique for epidemiological surveillance.
Efficacy and tolerability of intravenous methylergonovine in migraine female patients attending the emergency department: a pilot open-label study
Authors: Niño-Maldonado Alfredo I , Caballero-García Gary , Mercado-Bochero Wilfrido , Rico-Villademoros Fernando , Calandre Elena P 
Published: November 2009

Abstract

Background
Methylergonovine is an ergot alkaloid widely used in postpartum women. It is also an active metabolite of methysergide and previous studies suggest that it could be effective against refractory headache and cluster headache. The purpose of the present study was to assess the potential therapeutic effectiveness of methylergonovine in the emergency treatment of severe migraine.

Methods
One hundred and twenty five female patients with migraine attending the emergency department received 0.15 mg of methylergonovine intravenously. Pain intensity, heart rate, blood pressure, and methylergonovine side effects were checked 5, 10, 15, 30 and 60 minutes after drug administration. An additional 0.075 mg dose of methylergonovine was administered to those patients who did not experienced relevant pain relief 15 minutes after dosing.

Results
Pain intensity decreased markedly from the first minutes after dosing, the 74.4% of patients being pain free at 60 minutes. Only seven patients required an additional dose of methylergonovine. Nausea and vomiting were the most relevant side effects related with methylergonovine administration (84% of patients). A substantial decrease (10 to 25 mmHg) in systolic blood pressure values was observed in 56% of the patients. A significant correlation (p < 0.0001) was found between the decrease in pain intensity and the reduction of systolic blood pressure.

Conclusion
Although limited by the non-controlled design of the study, our data suggest that intravenous methylergonovine can be an effective and safe drug in the management of severe migraine attacks in the emergency room.
Analysis of Factors Influencing Outcome in Patients With In-Transit Malignant Melanoma Undergoing Isolated Limb Perfusion Using Modern Treatment Parameters
Authors: Alexander H. Richard , Fraker Douglas L. , Bartlett David L. , Libutti Steven K. , Steinberg Seth M. , Soriano Perry , Beresnev Tatiana 
Published: November 2009

Purpose In-transit disease afflicts approximately 10% of patients with extremity melanoma; no single treatment approach has been uniformly accepted as the most effective. We report long-term outcomes in patients with in-transit extremity melanoma who underwent isolated limb perfusion (ILP) in an era of increasingly accurate staging, uniform operative and treatment conditions, and regular long-term follow-up. Patients and Methods Between May 1992 and February 2005, 91 patients (median age, 57 years; 50 women, 41 men) underwent a 90-minute hyperthermic ILP (melphalan, 10 to 13 mg/L limb volume, tumor necrosis factor [TNF; n = 44], or interferon [n = 38]) using uniform operative technique and intraoperative leak monitoring. Patients were prospectively followed for response, in-field progression-free survival (PFS), and overall survival (OS). Parameters associated with in-field PFS and OS were analyzed by standard statistical methods. Results There was one operative death (1.1%). There were 62 complete responses (69%) and 23 partial responses (26%) in 90 assessable patients. At a median potential follow-up of 11 years, median in-field PFS was 12.4 months and median OS was 47.4 months; 5 and 10-year actuarial OS probabilities were 43% and 34%, respectively. Female sex and low tumor burden (≤ 20 lesions) were associated with prolonged in-field PFS (male:female hazard ratio [HR], 2.07; 95% CI, 1.27 to 3.38; 21+ v ≤ 20 tumors HR, 2.29; 95% CI, 1.21 to 4.34; P < .011 for both). Female sex was associated with improved OS (P = .027; male:female HR, 1.82; 95% CI, 1.07 to 3.09). Conclusion In appropriately selected patients, ILP has clinical benefit. The use of TNF was not associated with improved in-field PFS, while female sex was associated with better survival.
Thyroid Hormone Induced Brown Adipose Tissue and Amelioration of Diabetes in a Patient with Extreme Insulin Resistance
Authors: Skarulis Monica C. , Celi Francesco S. , Mueller Elisabetta , Zemskova Marina , Malek Rana , Hugendubler Lynne , Cochran Craig , Solomon Jeffrey , Chen Clara , Gorden Phillip 
Published: November 2009

AbstractContext: Brown adipose tissue (BAT) found by positron emission/computed tomography (PET-CT) using flouro-deoxyglucose (FDG) is inducible by cold exposure in men. Factors leading to increased BAT are of great interest for its potential role in the treatment of diabetes and obesity.Objective: We tested whether thyroid hormone (TH) levels are related to the volume and activity of BAT in a patient with a mutation in the insulin receptor gene.Design/Setting/Intervention: Our work was based on the case report of a patient in an observational study at the National Institutes of Health.Patient: The patient discontinued insulin and oral antidiabetics after thyroidectomy and suppressive-dose levothyroxine therapy for thyroid cancer. PET-CT uptake in BAT was confirmed by histology and molecular analysis.Outcomes: PET-CT studies were performed, and we measured hemoglobin A1c and resting energy expenditure before and after levothyroxine discontinuation for thyroid cancer testing. Molecular studies of BAT and white adipose samples are presented.Result: Supraclavicular and periumbilical sc adipose tissue demonstrated molecular features of BAT including uncoupling protein-1, type 2 deiodinase, and PR domain containing 16 by quantitative PCR. Activity of type 2 deiodinase activity was increased. The discontinuation of levothyroxine resulted in decreased FDG uptake and diminished volume of BAT depots accompanied by worsening of diabetic control.Conclusions: This case demonstrates the TH effect on BAT activity and volume in this patient and an association between BAT activity and glucose levels in this patient. Because the contribution of TH on skeletal muscle energy expenditure and fuel metabolism was not assessed, an association between BAT activity and glucose homeostasis can only be suggested.