bluuebunny/crossref_metadata_2025_split huggingface dataset:
Beneficial effect of rosuvastatin on cardiac dysfunction is associated with alterations in calcium‐regulatory proteins
Authors: Yang Ying , Mou Yun , Hu Shen‐Jiang , Fu Michael 
Published: January 2009

AimsThe normal expression of Ca2+‐regulatory protein is critical for efficient myocardial function. The present study tested the hypothesis that rosuvastatin treatment may attenuate left ventricular (LV) remodelling and dysfunction in the failing heart, which may be associated with alterations of Ca2+‐regulatory protein.Methods and resultsWe investigated the change of LV remodelling and function in a rat model of cardiac dysfunction due to myocardial infarction (MI) with or without rosuvastatin (10 mg/kg/day) treatment for 10 weeks. The protein expression of sarcoplasmic reticulum Ca2+ ATPase (SERCA)2a, phospholamban (PLB), and phospho‐PLB at serine‐16 (pSer16‐PLB), as well as SERCA activity, interleukin (IL)‐6, and IL‐10 levels were evaluated. After rosuvastatin treatment, LV remodelling and dysfunction were prevented. Rosuvastatin prevented the decrease of SERCA2a and pSer16‐PLB expression, increased SERCA activity, but showed no effect on PLB expression. Furthermore, rosuvastatin reduced the increased IL‐6 level and further elevated IL‐10 level in the peri‐infarct and remote zones of MI. Serum lipid levels remained unchanged.ConclusionRosuvastatin is effective in preventing LV remodelling and dysfunction in the failing heart. The molecular mechanism may be related to normalization of SERCA2a expression, SERCA activity, and pSer16‐PLB levels, as well as through cytokine alterations independent of its lipid‐lowering effect.
Adequacy of diagnosis and treatment of chronic heart failure in primary health care in Sweden
Authors: Dahlstrom Ulf , Hakansson Jan , Swedberg Karl , Waldenstrom Anders 
Published: January 2009

AimsWe performed an observational multicentre study to obtain information of the diagnostic tools and treatments currently used in patients with chronic heart failure (CHF) in primary health care (PHC) in Sweden. Data were collected from 2093 patients in 158 randomly selected PHC centres.Methods and resultsThe mean age was 79 years. The dominating aetiology of HF was hypertension and/or ischaemic heart disease. Diagnosis was based on symptoms and/or ECG and/or chest X‐ray in 69% of the patients. Treatment with a renin–angiotensin system (RAS) blocker was ongoing in 74% of the patients, but only 37% had ≥50% of the recommended target dose. In 68%, treatment with a beta‐blocker (BB) was present, but only 31% had ≥50% of the recommended target dose. Only 42% of the patients were on treatment with an RAS blocker and a BB and only 20% had ≥50% of the recommended target dose.ConclusionThe diagnostic criteria for CHF according to the European Society of Cardiology were fulfilled in only ~30% of the patients. In addition, evidenced‐based treatments to reduce morbidity and mortality were markedly underused, particularly regarding dosing. Our findings may reflect the patients’ high age and the presence of important co‐morbidities.
A randomized trial of the impact of strict glycaemic control on myocardial diastolic function and perfusion reserve: a report from the DADD (Diabetes mellitus And Diastolic Dysfunction) study
Authors: Jarnert Christina , Landstedt‐Hallin Lena , Malmberg Klas , Melcher Anders , Ohrvik John , Persson Hans , Rydén Lars 
Published: January 2009

AbstractAimsMyocardial diastolic dysfunction (MDD) and impaired coronary flow reserve (CFR) are early signs of myocardial involvement in patients with diabetes. The important question of whether this may be reversed by glucose normalization has not been tested in a controlled clinical trial. We hypothesized that strict glycaemic control, particularly if insulin based, will improve MDD and CFR.Methods and resultsThirty‐nine type 2 diabetes patients (mean age 61.0 ± 7 years) with signs of diastolic dysfunction were randomly assigned to strict metabolic control by insulin (I‐group; n = 21) or oral glucose lowering agents (O‐group; n = 18). MDD and CFR were studied with Doppler‐echocardiography including Tissue Doppler Imaging and myocardial contrast enhanced echocardiography. Fasting glucose (I‐group = −2.2 ± 2.1; O‐group −1.5 ± 0.8 mmol/L) and HbA1c were normalized (−0.6 ± 0.4 and −0.7 ± 0.4%, respectively) in both groups, but this did not significantly improve MDD in either of the groups (P = 0.65). There was no difference in CFR before and after improved glycaemic control.ConclusionThe hypothesis that strict glycaemic control would reverse early signs of MDD and improve CFR in patients with type 2 diabetes could not be confirmed, despite achieved normalization. Whether it is possible to influence a more pronounced diastolic dysfunction, particularly in less well‐controlled diabetic patients, remains to be established.
Prevalence and prognostic significance of adrenergic escape during chronic β‐blocker therapy in chronic heart failure
Authors: Frankenstein Lutz , Zugck Christian , Schellberg Dieter , Nelles Manfred , Froehlich Hanna , Katus Hugo , Remppis Andrew 
Published: January 2009

AimsLike aldosterone escape to ACE‐inhibitors, adrenergic escape (AE) to β‐blockers appears conceivable in chronic heart failure (CHF), as generalized systemic neurohumoral activation has been described as the pathophysiological basis of this syndrome. The aim of this study was to examine the prevalence and prognostic value of AE with respect to different β‐blocker agents and doses.Methods and resultsThis was a prospective, observational study of 415 patients with systolic CHF receiving chronic stable β‐blocker therapy. AE was defined by norepinephrine levels above the upper limit of normal. Irrespective of the individual β‐blocker agents used and the dose equivalent taken, the prevalence of AE was 31–39%. Norepinephrine levels neither correlated with heart rate (r = 0.02; 95% CI: −0.08–0.11; P = 0.74) nor were they related to underlying rhythm (P = 0.09) or the individual β‐blocker agent used (P = 0.87). The presence of AE was a strong and independent indicator of mortality (adjusted HR: 1.915; 95% CI: 1.387–2.645; χ2: 15.60).ConclusionWe verified the presence of AE in CHF patients on chronic stable β‐blocker therapy, irrespective of the individual β‐blocker agent and the dose equivalent. As AE might indicate therapeutic failure, the determination of AE could help to identify those patients with CHF that might benefit from more aggressive treatment modalities. Heart rate, however, is not a surrogate for adrenergic escape.
Diagnosis of heart failure with preserved ejection fraction: improved accuracy with the use of markers of collagen turnover
Authors: Martos Ramón , Baugh John , Ledwidge Mark , O'Loughlin Christina , Murphy Niamh F. , Conlon Carmel , Patle Anil , Donnelly Seamas C. , McDonald Kenneth 
Published: January 2009

AimsHeart failure with preserved ejection fraction (HF‐PEF) can be difficult to diagnose in clinical practice. Myocardial fibrosis is a major determinant of diastolic dysfunction (DD), potentially contributing to the progression of HF‐PEF. The aim of this study was to analyse whether serological markers of collagen turnover may predict HF‐PEF and DD.Methods and resultsWe included 85 Caucasian treated hypertensive patients (DD n = 65; both DD and HF‐PEF n = 32). Serum carboxy (PICP), amino (PINP), and carboxytelo (CITP) peptides of procollagen type I, amino (PIIINP) peptide of procollagen type III, matrix metalloproteinases (MMP‐1, MMP‐2, and MMP‐9), and tissue inhibitor of MMP levels were assayed. Using receiver operating characteristic curve analysis, MMP‐2 (AUC = 0.91; 95% CI: 0.84, 0.98), CITP (0.83; 0.72, 0.92), PICP (0.82; 0.72, 0.92), B‐type natriuretic peptide (BNP) (0.82; 0.73, 0.91), MMP‐9 (0.79; 0.68, 0.89), and PIIINP (0.78; 0.66, 0.89) levels were significant predictors of HF‐PEF (P < 0.01 for all). Carboxytelo peptides of procollagen type I (AUC = 0.74; 95% CI: 0.62, 0.86), MMP‐2 (0.73; 0.62, 0.84), PIIINP (0.73; 0.60, 0.85), BNP (0.69; 0.55, 0.83) and PICP (0.66; 0.54, 0.78) levels were significant predictors of DD (P < 0.05 for all). A cutoff of 1585 ng/mL for MMP‐2 provided 91% sensitivity and 76% specificity for predicting HF‐PEF and combinations of biomarkers could be used to adjust either sensitivity or specificity.ConclusionMarkers of collagen turnover identify patients with HF‐PEF and DD. Matrix metalloproteinase 2 may be more useful than BNP in the identification of HF‐PEF. This suggests that these new biochemical tools may assist in identifying patients with these diagnostically challenging conditions.
Diaphragm Training in Amyotrophic Lateral Sclerosis
Authors: Nardin Rachel , O'Donnell Carl , Loring Stephen H , Nie Rui , Hembre Kristi , Walsh Joy , Arboleda Barbara Wilson , Muzikansky Alona , Nguyen Dang , Raynor Elizabeth 
Published: January 2009

Abstract

There is a continued need for therapies to improve respiratory function and quality of life in patients with amyotrophic lateral sclerosis. In this pilot trial, we studied 8 subjects with amyotrophic lateral sclerosis and respiratory involvement. We measured respiratory function and quality of life at baseline. We then taught subjects diaphragm training, a method of breath control designed to improve respiratory muscle strength and efficiency. We repeated measures of respiratory function and quality of life 6 and 12 weeks later. There was no significant improvement in any outcome measure after instituting diaphragm training. There was a nonsignificant trend toward a slower rate of decline in respiratory function in those subjects who mastered the technique; however, only half the subjects were able to successfully change their pattern of breathing. A larger study of this technique is warranted; however, in determining the sample size for a larger study, the difficulty for patients in mastering the technique must be taken into consideration.
What's in the Literature?
Authors: Simmons Zachary 
Published: January 2009

Abstract

The term “therapy” always is welcome when dealing with neuromuscular diseases, and I am pleased to report that the literature this quarter contains articles on promising treatments for muscle diseases, including some very exciting work on gene therapy. Over the past several years, genetics have assumed increasing importance in the neuromuscular literature, and this is apparent not only from the gene therapy article but also from articles on the genetics of so-called “sporadic” amyotrophic lateral sclerosis. There are also important studies reminding us that neuromuscular diseases have manifestations beyond the nervous system. Studies on statins described below will undoubtedly lead clinicians to reassess the frequently asked questions about the use of these agents in patients with neuromuscular disorders. Finally, peripheral neuropathies and some natural history and classification studies round out this issue's review.
Population pharmacokinetics of intravenous pantoprazole in paediatric intensive care patients
Authors: Pettersen Géraldine , Mouksassi Mohamad‐Samer , Théorêt Yves , Labbé Line , Faure Christophe , Nguyen Bao , Litalien Catherine 
Published: January 2009

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • The use of intravenous pantoprazole, a proton pump inhibitor, has been increasing in the paediatric intensive care unit.• Despite this increased use, data on the disposition of intravenous pantoprazole in paediatric intensive care patients are very scarce. WHAT THIS STUDY ADDS • Our population approach has determined the pharmacokinetic parameters of intravenous pantoprazole in paediatric intensive care patients and the relative importance of factors influencing its disposition.• Pantoprazole clearance was significantly influenced by developmental changes and by the presence of systemic inflammatory syndrome, hepatic dysfunction and CYP2C19 inhibitors.AIMSTo characterize the pharmacokinetics of intravenous pantoprazole in a paediatric intensive care population and to determine the influence of demographic factors, systemic inflammatory response syndrome (SIRS), hepatic dysfunction and concomitantly used CYP2C19 inducers and inhibitors on the drug's pharmacokinetics.METHODSA total of 156 pantoprazole concentration measurements from 20 patients (10 days to 16.4 years of age) at risk for or with upper gastrointestinal bleeding, who received pantoprazole doses ranging from 19.9 to 140.6 mg/1.73 m2/day, were analysed using a population pharmacokinetic approach (nonmem program).RESULTSThe best structural model for pantoprazole was a two‐compartment model with zero order infusion and first‐order elimination. Body weight, SIRS, age, hepatic dysfunction and presence of CYP2C19 inhibitors were significant covariates affecting clearance (CL), accounting for 75% of interindividual variability. Only body weight significantly influenced central volume of distribution (Vc). In the final population model, the estimated CL and Vc were 5.28 l h−1 and 2.22 l, respectively, for a typical 5‐year‐old child weighing 20 kg. Pantoprazole CL increased with weight and age, whereas the presence of SIRS, CYP2C19 inhibitors and hepatic dysfunction, when present separately, significantly decreased pantoprazole CL by 62.3, 65.8 and 50.5%, respectively. For patients aged between 6 months and 5 years without SIRS, CYP2C19 inhibitor or hepatic dysfunction, the predicted pantoprazole CL is faster than that reported in adults.CONCLUSIONThese results provide important information for physicians regarding selection of a starting dose and dosing regimens of pantoprazole for paediatric intensive care patients based on factors frequently encountered in this population.
Lack of age and gender effects on single‐dose pharmacokinetics of tomopenem (RO4908463/CS‐023), a novel carbapenem
Authors: Mallalieu Navita L. , Lennon Siân , Guy Thorold , Liu Mei , Luedin Eric , Davies Brian E. 
Published: January 2009

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • This compound belongs to a well‐described class of antibacterials, the carbapenems, which are characterized by excellent bactericidal activity.• This compound is unique in that it has activity against methicillin‐resistant Staphylococcus aureus and Pseudomonas aeruginosa.• The pharmacokinetics (PK) of all molecules in this class is characterized by short plasma half‐lives and renal elimination as the major source of clearance.• Age‐ and gender‐related effects on renal and hepatic function have been shown to necessitate adjustments in dosing regimens to ensure safe and efficacious exposures to drugs. WHAT THIS STUDY ADDS • The extent of changes in PK of tomopenem in the elderly and women is minor when compared with healthy male volunteers, so dose adjustments are not necessary.• Instead of age or gender, creatinine clearance can be used to explain the slight effect of these variables on PK.AIMS To investigate the effect of age and gender on the tolerability, safety and pharmacokinetics (PK) of tomopenem (RO4908463/CS‐023), a novel carbapenem antibiotic, and its major metabolite.METHODS Forty‐two subjects were assigned to one of the following three groups: young men, elderly men and elderly women. The PK, safety and tolerability of an intravenous infusion of 1500 mg tomopenem and its resultant major metabolite (open beta‐lactam ring) were assessed.RESULTS Minor differences in exposure of both tomopenem and the major metabolite were seen. The area under the curve (AUC) of tomopenem was 22% higher in elderly men compared with young men, and 19% higher in elderly women relative to the elderly men. Total clearance of tomopenem decreased with decreasing creatinine clearance. In the two male groups, renal clearance values of tomopenem were similar (3.52 and 3.67 l h−1) and higher than in the elderly female group (2.83 l h−1). The mean half‐lives ranged from 2.03 (healthy young men) to 2.41 h (elderly men). The difference in AUC of tomopenem can be explained by differences in the mean creatinine clearances of 116 (young men), 101 (elderly men) and 84.7 (elderly women) ml min−1 1.73 m−2, respectively.CONCLUSIONS While some PK parameters were statistically different among the three groups, the differences were mostly minor and unlikely to be clinically meaningful. The difference in the PK can be largely attributed to the difference in creatinine clearance of these groups.
Airway angiogenesis in patients with rhinitis and controlled asthma
Authors: Kristan S. S. , Malovrh M. M. , Silar M. , Kern I. , Flezar M. , Kosnik M. , Suskovic S. , Korosec P. 
Published: January 2009

SummaryBackground
Airway angiogenesis may be an important part of structural remodelling in the pathogenesis of asthma. The development of asthma is frequently preceded by rhinitis.Objective
We sought to determine whether the levels of angiogenesis‐related factors are elevated in airways of patients with rhinitis or controlled asthma.Methods
We analysed the induced sputum of 18 rhinitis patients, 16 asthmatic patients, and 15 healthy controls. The concentrations of angiogenin, vascular endothelial growth factor (VEGF), IL‐8, fibroblast growth factor (bFGF), and TNF‐α were measured by cytometric bead arrays.Results
We found significantly increased angiogenin and VEGF concentrations in the induced sputum supernatant of both rhinitis and asthma patients compared with that of the healthy control group (P0.0005). With the exception of TNF‐α, there was no difference in the other angiogenic factors; TNF‐α levels were higher in the rhinitis group than in the control group (P=0.02).Conclusion
These in vivo results suggest increased airway angiogenesis in patients with rhinitis without asthma as well as in corticosteroid‐treated and well‐controlled asthma patients.
Beta lactam allergy and resensitization in children with suspected beta lactam allergy
Authors: Hershkovich J. , Broides A. , Kirjner L. , Smith H. , Gorodischer R. 
Published: January 2009

SummaryBackground
In patients who were clinically diagnosed as having beta lactam allergy and had negative skin tests, the rates of reported resensitization to beta lactams after subsequent exposures, vary significantly. Some allergists advocate skin testing before every exposure to beta lactams.Objective
We sought to determine the true rate of beta lactam allergy and of resensitization in children with a positive history for suspected beta lactam allergy.Methods
The study was conducted from July 1998 to May 2004, with follow‐up during 2007. Beta lactam allergy tests with the major determinant and freshly prepared minor determinant mixtures were offered to history positive children. Negative skin tests were followed by oral challenge. The tests were performed again 1–5 months later in order to address the possibility of resensitization.Results
Tests were performed on 166 children: 150 for penicillins alone, 14 for penicillin in combination with cephalosporins, and an additional 2 patients solely for cephalosporins. Only 10 children (6%) were positive in the initial evaluation, four by skin test and six by oral challenge. A second set of tests was performed in 98 children with a negative initial evaluation; only two children (2%) were resensitized. On a follow‐up survey of 71 of the 96 patients, 59 (83%) had received beta lactams; only one had developed a minor rash after subsequent exposure to amoxicillin.Conclusions
Most children with suspected beta lactam allergy were not allergic to beta lactams. Resensitization to beta lactam antibiotics in children in this study was infrequent. In children with a clinical diagnosis of beta lactam allergy and negative skin tests, repeated skin testing before every exposure is usually unnecessary.
Animal models of protein allergenicity: potential benefits, pitfalls and challenges
Authors: Dearman R. J. , Kimber I. 
Published: January 2009

SummaryFood allergy is an important health issue. With an increasing interest in novel foods derived from transgenic crop plants, there is a growing need for the development of approaches suitable for the characterization of the allergenic potential of proteins. There are methods available currently (such as homology searches and serological testing) that are very effective at identifying proteins that are likely to cross‐react with known allergens. However, animal models may play a role in the identification of truly novel proteins, such as bacterial or fungal proteins, that have not been experienced previously in the diet. We consider here the potential benefits, pitfalls and challenges of the selection of various animal models, including the mouse, the rat, the dog and the neonatal swine. The advantages and disadvantages of various experimental end‐points are discussed, including the measurement of specific IgE by ELISA, Western blotting or functional tests such as the passive cutaneous anaphylaxis assay, and the assessment of challenge‐induced clinical symptoms in previously sensitized animals. The experimental variables of route of exposure to test proteins and the incorporation of adjuvant to increase the sensitivity of the responses are considered also. It is important to emphasize that currently none of these approaches has been validated for the purposes of hazard identification in the context of a safety assessment. However, the available evidence suggests that the judicious use of an accurate and robust animal model could provide important additional data that would contribute significantly to the assessment of the potential allergenicity of novel proteins.
The impact of chemokine receptor CX3CR1 deficiency during respiratory infections with Mycobacterium tuberculosis or Francisella tularensis
Authors: Hall J D , Kurtz S L , Rigel N W , Gunn B M , Taft-Benz S , Morrison J P , Fong A M , Patel D D , Braunstein M , Kawula T H 
Published: January 2009

Summary
Recruitment of immune cells to infection sites is a critical component of the host response to pathogens. This process is facilitated partly through interactions of chemokines with cognate receptors. Here, we examine the importance of fractalkine (CX3CL1) receptor, CX3CR1, which regulates function and trafficking of macrophages and dendritic cells, in the host's ability to control respiratory infections with Mycobacterium tuberculosis or Francisella tularensis. Following low-dose aerosol challenge with M. tuberculosis, CX3CR1−/− mice were no more susceptible to infection than wild-type C57BL/6 mice as measured by organ burden and survival time. Similarly, following inhalation of F. tularensis, CX3CR1−/− mice displayed similar organ burdens to wild-type mice. CX3CR1−/− mice had increased recruitment of monocytes and neutrophils in the lung; however, this did not result in increased abundance of infected monocytes or neutrophils. We conclude that CX3CR1-deficiency affects immune-cell recruitment; however, loss of CX3CR1 alone does not render the host more susceptible to M. tuberculosis or F. tularensis.