Home About us Contact
|
Home About us Contact | ||
|
|
||
Similar Regardless (similar + regardless)
Selected AbstractsClinical and Hemodynamic Effects of Nesiritide (B-Type Natriuretic Peptide) in Patients With Decompensated Heart Failure Receiving , BlockersCONGESTIVE HEART FAILURE, Issue 2 2005William T. Abraham MD The use of , blockers in congestive heart failure presents a therapeutic challenge for patients with acute episodes of decompensation. Such patients may be less responsive to positive inotropic agents, whereas the beneficial effects of nesiritide, which are not dependent on the ,-adrenergic receptor signal-transduction pathway, may be preserved. This analysis of the Vasodilation in the Management of Acute CHF trial evaluated the safety and efficacy of nesiritide in decompensated congestive heart failure patients receiving , blockers. The Vasodilation in the Management of Acute CHF trial was a multicenter, randomized, controlled evaluation of nesiritide in 489 hospitalized patients with decompensated congestive heart failure. One hundred twenty-three patients were on chronic ,-blocker therapy at enrollment (31 randomized to placebo, 50 to nesiritide, and 42 to nitroglycerin). Primary end points included pulmonary capillary wedge pressure and dyspnea evaluation at 3 hours. Patients receiving nesiritide, but not IV nitroglycerin, had significantly reduced pulmonary capillary wedge pressure vs. placebo at 3 hours regardless of ,-blocker use. The use of , blockers did not alter the beneficial effects of nesiritide on systemic blood pressure, heart rate, or dyspnea evaluation. In nesiritide-treated subjects, safety profiles were similar regardless of ,-blocker use. Thus, the clinical and hemodynamic benefits and safety of nesiritide are preserved in decompensated congestive heart failure patients receiving chronic , blockade. [source] The definition of opioid-related deaths in Australia: implications for surveillance and policyDRUG AND ALCOHOL REVIEW, Issue 5 2005MARIANNE E. JAUNCEY Abstract The reported number of deaths caused by opioid use depends on the definition of an opioid-related death. In this study, we used Australian Bureau of Statistics (ABS) mortality data to illustrate how choice of classification codes used to record cause of death can impact on the statistics reported for national surveillance of opioid deaths. Using International Classification of Diseases version 10 (ICD-10) codes from ABS mortality data 1997,2002, we examined all deaths where opioids were reported as a contributing or underlying cause. For the 6-year period there was a total of 5839 deaths where opioids were reported. Three possible surveillance definitions of accidental opioid-related deaths were examined, and compared to the total number of deaths where opioids were reported for each year. Age restrictions, often placed on surveillance definitions, were also examined. As expected, the number of deaths was higher with the more inclusive definitions. Trends in deaths were found to be similar regardless of the definition used; however, a comparison between Australian states revealed up to a twofold difference in the absolute numbers of accidental opioid-related deaths, depending on the definition. Any interpretation of reported numbers of opioid deaths should specify any restrictions placed on the data, and describe the implications of definitions used. [source] Regulatory T cells in human geohelminth infection suppress immune responses to BCG and Plasmodium falciparumEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 2 2010Linda J. Wammes Abstract Chronic helminth infections induce T-cell hyporesponsiveness, which may affect immune responses to other pathogens or to vaccines. This study investigates the influence of Treg activity on proliferation and cytokine responses to BCG and Plasmodium falciparum -parasitized RBC in Indonesian schoolchildren. Geohelminth-infected children's in vitro T-cell proliferation to either BCG or pRBC was reduced compared to that of uninfected children. Although the frequency of CD4+CD25hiFOXP3+ T cells was similar regardless of infection status, the suppressive activity differed between geohelminth-infected and geohelminth-uninfected groups: Ag-specific proliferative responses increased upon CD4+CD25hi T-cell depletion in geohelminth-infected subjects only. In addition, IFN-, production in response to both BCG and parasitized RBC was increased after removal of CD4+CD25hi T cells. These data demonstrate that geohelminth-associated Treg influence immune responses to bystander Ag of mycobacteria and plasmodia. Geohelminth-induced immune modulation may have important consequences for co-endemic infections and vaccine trials. [source] Foliar susceptibility of eastern oak species to Phytophthora infectionFOREST PATHOLOGY, Issue 5 2008Y. Balci Summary Seven different Phytophthora species were used to test the foliar susceptibility of the common eastern US oak species and understory plants to Phytophthora infection. The Phytophthora species employed were Phytophthora cambivora, Phytophthora cinnamomi, Phytophthora citricola, Phytophthora europaea, Phytophthora quercetorum, Phytophthora quercina -like and Phytophthora sp1. Inoculation of detached-leaves with agar plugs containing mycelia of Phytophthora provided an estimate of their relative susceptibility. Lesions were always greater when foliage was wounded and young. On deciduous plants, lesion sizes were considerably reduced with the increasing foliar age, although with evergreen plants lesion sizes remained similar regardless of foliar age when more aggressive isolates were tested. Infections seldom resulted when foliage was not wounded. With young and mature foliage, P. citricola usually produced the largest lesions. Young foliage of Quercus rubra was the most susceptible to infection followed by Castanea dentata for both wounded and non-wounded inoculations. Mature foliage of Hamamelis virginiana, Kalmia latifolia and Quercus alba were the most susceptible to wound and non-wound inoculations. [source] Health status impairment and costs associated with COPD exacerbation managed in hospitalINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 7 2007J. F. O'Reilly Summary Exacerbations of chronic obstructive pulmonary disease (COPD) have serious health consequences for patients and are strongly associated with unscheduled healthcare resource use. This study used a preference-based quality of life measure questionnaire (EQ-5D) to evaluate the impact of exacerbation on health status and utility during a patient's admission to hospital and short-term follow-up. Costs of admission were calculated. In total, 149 patients consented to take part in the study representing 222 admissions to hospital. At admission patients reported high levels of problems for all dimensions of the EQ-5D. Mean utility (,0.077) and Visual Analogue Scale (25.9) values indicated great impairment, with 61% of patients having a negative utility value representing a health state equivalent to ,worse than death' at admission. Many problems were still reported at discharge. By 3 months follow-up patients had deteriorated, with percentages of patients reporting problems in mobility (98%) and usual activity (88%) almost back up to admission levels. Health status and utility values were similar regardless of lung function at admission and at discharge. Approximately half of the patients in each category had a negative utility value at admission representing a health state ,worse than death', with similar levels of improvement by discharge. The mean cost of an admission was £2130.34 (SD 1326.09) with only a mean of £110.37 (5%) because of medication. No differences were noted by lung function category. In conclusion, all COPD patients requiring admission for an exacerbation suffer a serious deterioration in health status which, although improves during admission, notably deteriorates by 3 months postdischarge. [source] Measurement matters for modelling US import prices,INTERNATIONAL JOURNAL OF FINANCE & ECONOMICS, Issue 2 2009Charles P. Thomas Abstract We focus on capturing the increasingly important role that emerging economies play in determining US import prices. Emerging-market producers differ from others in two respects: (1) their cost structure is well below that of developed-market producers, and (2) their wide profit margins induce pricing policies that seek to exhaust production capacity. We argue that these features have dampened the short-run responses of import prices to changes in the value of the dollar but that they have not altered the associated long-run response. To capture these considerations, we develop a new method to measure foreign prices and adopt a formulation that differentiates between short- and long-run responses. Our econometric work asks two questions: First, can one replicate the literature's dispersion of pass-through estimates? Second, is there any evidence of a change in the dynamic response of import prices to changes in the exchange value of the dollar? To address the first question, we estimate the parameters of our models using several alternative measures of US and foreign prices, dynamic specifications, and sample periods. We find that these alternative inputs translate into a large range of parameter estimates, a finding that helps to rationalizing the existing dispersion of estimates. To address the second question, we compute the implied dynamic adjustment of import prices to a change in the value of the dollar using parameters estimated from two samples: 1974,2000 and 1974,2005. The long-run response of import prices is similar regardless of which sample is used,roughly one-half of the change in the exchange rate is passed through to import prices. However, the short,run response is quite sensitive to the sample period. Specifically, the short-run response based on data through 2005 is smaller than the short-run response based on data through 2000. We argue that one force behind the change in dynamics of the import-price process is the greater presence of producers from emerging economies and that their effect on import prices can be captured with their measure of foreign prices. Published in 2008 by John Wiley & Sons, Ltd. [source] Relation between self-knowledge reference and self-monitoring of emotional state1JAPANESE PSYCHOLOGICAL RESEARCH, Issue 3 2007TAKASHI NAKAO Abstract:, We used a task facilitation paradigm to examine whether self-knowledge reference and self-monitoring have a functional relationship. Eighteen participants performed a series of tasks: self-knowledge reference, evaluation, self-monitoring, and semantic. Responses on the self-knowledge reference task were faster when the previous task was self-monitoring rather than semantic. However, responses on the self-monitoring task were similar regardless of whether it was preceded by the self-knowledge reference task or the evaluation task. Our results suggest that self-monitoring induces self-knowledge reference. [source] Tissue reaction and biodegradation of implanted cross-linked high amylose starch in ratsJOURNAL OF BIOMEDICAL MATERIALS RESEARCH, Issue 6 2002Cyril Désévaux Abstract The biocompatibility and degradation characteristics of cross-linked high amylose starch (Contramid®) were investigated in rats over 4 months. Contramid® pellets (3-mm diameter and thickness) obtained by direct compression, were implanted subcutaneously and intramuscularly. On sequential time points, macroscopic observations of implantation sites were performed and tissue samples were removed, fixed, and histologically evaluated. No macroscopic inflammatory reaction was observed with Contramid®. Upon histologic examination, inflammatory reaction produced by Contramid® was moderate and restricted to implantation sites. The sequence of inflammatory events with Contramid® was similar regardless of implantation site. Degradation of Contramid® pellets was characterized by fragmentation with formation of fibrovascular septa and phagocytosis by macrophages. Finally Contramid® was mostly absorbed by the end of the 4-month period and substituted by adipocytes. It has been demonstrated that Contramid® is a biocompatible and absorbable material. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res (Appl Biomater) 63: 772,779, 2002 [source] Analysis of the Pattern of Initiation of Sustained Ventricular Arrhythmias in Patients with Implantable DefibrillatorsJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 7 2000ERIC TAYLOR M.D. Initiation of Sustained Ventricular Arrhythmias. Introduction: The purpose of this study was to analyze the pattern of initiation of sustained ventricular arrhythmias in patients with varying types of underlying structural heart disease. Methods and Results: The study group consisted of 90 patients with an implantable cardioverter defibrillator. Cardiovascular diagnoses included coronary artery disease in 64 patients (71%). The patients were divided into four groups based on the type and severity of structural heart disease. Two hundred sixty episodes of sustained ventricular arrhythmias were analyzed. The mean coupling interval of the initiating heat of all ventricular arrhythmias was 523 ± 171 msec. The coupling interval of the initiating beat was longer in patients with impaired ventricular function, particularly those with nonischemic dilated cardiomyopathy. The prematurity index was similar regardless of the type of underlying structural heart disease. However, the prematurity index was shorter in patients with polymorphic ventricular tachycardia (VT) compared to those with monomorphic VT. A pause was observed more commonly before the onset of polymorphic VT/ventricular fibrillation than sustained monomorphic VT. Two hundred twenty-two (85%) of the arrhythmia episodes were initiated by a late-coupled premature beat, 33 (13%) were initiated by an early-coupled premature beat, and 5 episodes (2%) were initiated with a short-long-short sequence. The patttern of initiation of the ventricular arrhythmias was similar in all patient groups and for both monomorphic and polymorphic tachycardias. Conclusion: These findings demonstrate that sustained ventricular arrhythmias typically are initiated by late-coupled ventricular premature depolarizations, regardless of the type or severity of underlying structural heart disease or resultant arrhythmia. [source] Impact of human coronavirus infections in otherwise healthy children who attended an emergency department,JOURNAL OF MEDICAL VIROLOGY, Issue 12 2006Susanna Esposito Abstract This prospective clinical and virological study of 2,060 otherwise healthy children aged <15 years of age (1,112 males; mean age,±,SD, 3.46,±,3.30 years) who attended the Emergency Department of Milan University's Institute of Pediatrics because of an acute disease excluding trauma during the winter season 2003,2004 was designed to compare the prevalence and clinical importance of human coronaviruses (HCoVs) in children. Real-time polymerase chain reaction (PCR) in nasopharyngeal aspirates revealed HCoV infection in 79 cases (3.8%): 33 HCoV-229E (1.6%), 13 HCoV-NL63 (0.6%), 11 HCoV-OC43 (0.5%), none HCoV-HKU1 genotype A, and 22 (1.1%) co-detections of a HCoV and another respiratory virus. The HCoVs were identified mainly in children with upper respiratory tract infection; there was no significant difference in clinical presentation between single HCoV infections and HCoV co-infections. Diagnostic methods were used in a limited number of patients, and the therapy prescribed and clinical outcomes were similar regardless of the viral strain. There were a few cases of other members of the households of HCoV-positive children falling ill during the 5,7 days following enrollment. These findings suggest that HCoV-229E and HCoV-OC43 have a limited clinical and socioeconomic impact on otherwise healthy children and their household contacts, and the HCoV-NL63 identified recently does not seem to be any different. The quantitative and qualitative role of HCoV-HKU1 genotype A is apparently very marginal. J. Med. Virol. 78:1609,1615, 2006. © 2006 Wiley-Liss, Inc. [source] Homeostasis of neuroactive amino acids in cultured cerebellar and neocortical neurons is influenced by environmental cuesJOURNAL OF NEUROSCIENCE RESEARCH, Issue 1-2 2005Helle Waagepetersen Abstract Neuronal function is highly influenced by the extracellular environment. To study the effect of the milieu on neurons from cerebellum and neocortex, cells from these brain areas were cultured under different conditions. Two sets of cultures, one neocortical and one cerebellar neurons, were maintained in media containing [U- 13C]glucose for 8 days at initial concentrations of 12 and 28 mM glucose, respectively. Other sets of cultures (8 days in vitro) maintained in a medium containing initially 12 mM glucose were incubated subsequently for 4 hr either by addition of [U- 13C]glucose to the culture medium (final concentration 3 mM) or by changing to fresh medium containing [U- 13C]glucose (3 mM) but without glutamine and fetal calf serum. 13C Nuclear magnetic resonance (NMR) spectra revealed extensive ,-aminobutyric acid (GABA) synthesis in both cultured neocortical and cerebellar neurons after maintenance in medium containing [U- 13C]glucose for 8 days, whereas no aspartate labeling was observed in these spectra. Mass spectrometry analysis, however, revealed high labeling intensity of aspartate, which was equal in the two types of neurons. Addition of [U- 13C]glucose (4 hr) on Day 8 in culture led to a similar extent of labeling of GABA in neocortical and in cerebellar cultures, but the cellular content of GABA was considerably higher in the neocortical neurons. The cellular content of alanine was similar regardless of culture type. Comparing the amount of labeling, however, cerebellar neurons exhibited a higher capacity for alanine synthesis. This is compatible with the fact that cerebellar neurons could ameliorate a low alanine content after culturing in low glucose (12 mM) by a 4-hr incubation in medium containing 3 mM glucose. A low glucose concentration during the culture period and a subsequent medium change were associated with decreases in glutathione and taurine contents. Moreover, glutamate and GABA contents were reduced in cerebellar cultures under either of these conditions. In neocortical neurons, the GABA content was decreased by simultaneous exposure to low glucose and change of medium. These conditions also led to an increase in the aspartate content in both types of cultures, although most pronounced in the neocortical neurons. Further experiments are needed to elucidate these phenomena that underline the impact of extracellular environment on amino acid homeostasis. © 2004 Wiley-Liss, Inc. [source] Comparing Structural Equation Models That Use Different Measures of the Level of Response to AlcoholALCOHOLISM, Issue 5 2010Marc A. Schuckit Background:, The two measures of a low level of response (LR) to alcohol, an alcohol challenge and the retrospective Self-Report of the Effects of Alcohol questionnaire (SRE), each identify individuals at high risk for heavy drinking and alcohol problems. These measures also perform similarly in identifying subjects with unique functional brain imaging characteristics. However, few data are available regarding whether alcohol challenge-based and SRE-based LRs operate similarly in structural equation models (SEMs) that search for characteristics, which help to mediate how LR impacts alcohol outcomes. Methods:, Two hundred and ninety-four men from the San Diego Prospective Study were evaluated for their LR to alcohol using alcohol challenges at ,age 20. At ,age 35, the same subjects filled out the SRE regarding the number of drinks needed for effects 15 to 20 years earlier. The two different LR scores for these men were used in SEM analyses evaluating how LR relates to future heavy drinking and to drinking in peers (PEER), alcohol expectancies (EXPECT), and drinking to cope (COPE) as potential mediators of the LR to drinking pattern (ALCOUT) relationships. Results:, While the 2 LR measures that were determined 15 years apart related to each other at a modest level (r = 0.17, p < 0.01), the SEM results were similar regardless of the LR source. In both alcohol challenge-based and SRE-based LR models, LR related directly to ALCOUT, with partial mediation from PEER and COPE, but not through EXPECT in these 35-year-old men. Conclusions:, Consistent with the >60% overlap in prediction of outcomes for the 2 LR measures, and with results from functional brain imaging, alcohol challenge- and SRE-based LR values operated similarly in SEM models in these men. [source] The use of numerical weather forecast model predictions as a source of data for irrigation modellingMETEOROLOGICAL APPLICATIONS, Issue 4 2005A. Venäläinen The use of numerical weather forecast model data as a source of data for soil moisture modelling was tested. Results show that the potential evaporation calculated using the Penman-Monteith equation can be estimated accurately using data obtained from the output of a high resolution numerical atmospheric model (HIRLAM, High Resolution Limited Area Model). The mean bias error was 0.26 mm for a 36-hour sum and the root mean square error was 2.14 mm. The evaporation obtained directly from HIRLAM was systematically smaller because this direct model output represents the real evaporation rather than the potential evaporation. The precipitation forecasts were less accurate. When the accuracy of parameters required for the calculation of potential evaporation were studied for one station, no serious bias was found. When two different irrigation models (AMBAV and SWAP) were run over one summer using either measured or HIRLAM data as the input, the results given by the models were quite similar regardless of input data source. The largest differences between the model outputs were caused by the formulation of crop and soil characteristics in the irrigation models. Copyright © 2005 Royal Meteorological Society [source] Sensory potentials evoked by tactile stimulation of different indentation velocities at the finger and palmMUSCLE AND NERVE, Issue 9 2001Masayuki Baba MD Abstract Previous studies suggest that the rate of indentation of a tactile probe determines which skin mechanoreceptors are activated. To further investigate this possibility, indentations of 300 ,m at velocities of 100 (T100) and 400 ,m/ms (T400) were applied to the tip (FT) and the proximal phalanx of digit III (PP) and the thenar eminence (Pm) of ten healthy volunteers, and compared with responses after electrical stimulation at the FT. Compound sensory action potentials (CSAPs) were recorded from the median nerve through needle electrodes at the wrist and elbow. The maximal sensory conduction velocities (SNCVs) between wrist and elbow were similar with electrical and T400 stimulation, but on average were 15% lower with T100 stimulation (P < 0.001). With both indentation velocities, SNCVs were similar regardless of stimulation sites. Amplitudes of tactile CSAPs with FT stimulation were 1,2 ,V at T400 and 0.3,0.4 ,V at T100. The CSAP areas evoked by T100 stimulation showed a reduction from fingertip to proximal finger to palm (P < 0.05,0.005), whereas those obtained with T400 stimulation showed a reduction only at the palm (P < 0.05). The results support previous studies indicating that fast indentation at 400 ,m/ms activated deeply placed Pacinian corpuscles as well as superficially situated Meissner corpuscles, whereas slower indentation at 100 ,m/ms activated primarily Meissner corpuscles. © 2001 John Wiley & Sons, Inc. Muscle Nerve 24: 1213,1218, 2001 [source] Relationship between the Duration of the Basal QRS Complex and Electrical Therapies for Ventricular Tachycardias among ICD PatientsPACING AND CLINICAL ELECTROPHYSIOLOGY, Issue 5 2010JAVIER JIMÉNEZ-CANDIL M.D., Ph.D. Background:,In implantable cardioverter-defibrillators (ICD) patients, the duration of the basal QRS complex (QRSd) is not associated with a greater risk of developing ventricular tachyarrhythmias. QRSd could be inversely related to the effectiveness of antitachycardia pacing (ATP) because it may be associated with longer conduction times of the paced-impulses and hence, with a greater propensity to require shocks to terminate ventricular tachycardias (VTs). Methods:,We followed 216 ICD patients (pacing site: right ventricular apex; QRSd , 100: 34%) for 21 ± 12 months. ICD programming was standardized. QRSd was determined on the electrocardiogram (50 mm/s) at device implantation. Results:,Five hundred and fifty-one VTs (cycle length: 329 ± 35 ms) occurred in 67 patients (36% had a QRSd , 100 ms). ATP terminated 86% of VTs and 11% needed shocks. Mean ATP efficiency per patient was 83%. QRSd was significantly correlated with the probability of successful ATP (C-coefficient: 0.66), the best cut-off point being 100 (sensitivity and specificity of 91% and 49%). Patients with QRSd , 100 had a higher ATP effectiveness (98% vs 75%; P = 0.003) and fewer VTs terminated by shocks (1% vs 23%; P = 0.003). By logistic regression, QRSd > 100 remained as an independent predictor of receiving shocks to terminate VTs (P = 0.01). According to Kaplan-Meier analysis, the occurrence of VTs was similar regardless of the QRSd (30% vs 38%; P = 0.2), but the incidence of shock due to VTs was higher in patients with a QRSd > 100 (19% vs 7%; P = 0.01). Conclusion:,Since QRSd is a negative and independent predictor of effective ATP, ICD patients with QRSd > 100 ms require shocks more frequently to terminate VTs. (PACE 2010; 596,604) [source] Age-related variations and sex differences in gender cleavage during middle childhoodPERSONAL RELATIONSHIPS, Issue 2 2001ROSANNE BURTON SMITH Gender cleavage, the segregation of the sexes, is a powerful phenomenon affecting socialization during childhood, but its developmental trajectory is far from clear. Sociometric responses by 299 boys and girls in Grades 3 to 6 from a group preference record were used to investigate age-related variations and sex differences in gender cleavage. Moreno's (1953) developmental model of gender cleavage was examined in the light of sociocultural changes, as well as advances in the theory and measurement of gender cleavage. Sex differences were found in same-gender preference, with older elementary girls showing greater same-gender preference than boys of the same age. However, this finding, plus the absence of gender differences in cross-gender evaluations, did not support more recent developmental accounts of gender cleavage. Linear trend analyses contradicted Moreno's basic precept of increasing same-gender preference between Grades 3 and 6. While same-gender acceptance and rejection were relatively similar regardless of grade level, cross-gender acceptance was greater in higher than in lower grades and the reverse was true for rejection. Furthermore, weaker gender cleavage effects in rejection data than in acceptance data suggested that strong same-gender liking does not infer equally robust cross-gender dislike. Gender cleavage appears to be relative rather than absolute. A more complex model is proposed incorporating sex differences as well as rejection evaluations [source] The Impact of Hurricane Katrina on the Mental and Physical Health of Low-Income Parents in New OrleansAMERICAN JOURNAL OF ORTHOPSYCHIATRY, Issue 2 2010Jean Rhodes The purpose of this study was to document changes in mental and physical health among 392 low-income parents exposed to Hurricane Katrina and to explore how hurricane-related stressors and loss relate to post-Katrina well-being. The prevalence of probable serious mental illness doubled, and nearly half of the respondents exhibited probable posttraumatic stress disorder. Higher levels of hurricane-related loss and stressors were generally associated with worse health outcomes, controlling for baseline sociodemographic and health measures. Higher baseline resources predicted fewer hurricane-associated stressors, but the consequences of stressors and loss were similar regardless of baseline resources. Adverse health consequences of Hurricane Katrina persisted for a year or more and were most severe for those experiencing the most stressors and loss. Long-term health and mental health services are needed for low-income disaster survivors, especially those who experience disaster-related stressors and loss. [source] Detailed ECG Analysis of Atrial Repolarization in HumansANNALS OF NONINVASIVE ELECTROCARDIOLOGY, Issue 1 2009Fredrik Holmqvist M.D., Ph.D. Introduction: Data on human atrial repolarization are scarce since the QRS complex normally obscures its ECG trace. In the present study, consecutive patients with third-degree AV block were studied to better describe the human Ta wave. Methods and Results: Forty patients (mean age 75 years, 17 men) were included. All anti-arrhythmic drugs were discontinued before ECG recording. Standard 12-lead ECGs were recorded, transformed to orthogonal leads and studied using signal-averaged P wave analysis. The average P wave duration was 124 ± 16 ms. The PTa duration was 449 ± 55 ms (corrected PTa 512 ± 60 ms) and the Ta duration (P wave end to Ta wave end) was 323 ± 56 ms. The polarity of the Ta wave was opposite to that of the P wave in all leads. The Ta peaks were located at 196 ± 55 ms in Lead Y, 216 ± 50 ms in Lead X, and 335 ± 92 in Lead Z. No correlation was found between P wave duration and Ta duration, or between Ta peak amplitude and Ta duration. The morphology of the Ta wave was similar regardless of the interatrial conduction. Conclusions: The Ta wave has the opposite polarity, and the duration is generally two to three times that, of the P wave. Although the Ta peak may occasionally be located in the PQ interval during normal AV conduction, it is unlikely that enough information can be obtained from analysis of this segment to differentiate normal from abnormal atrial repolarization. Hence, an algorithm for QRST cancellation during sinus rhythm is needed to further improve analysis. [source] Chronic Pharmacological and Safety Evaluation of HematideÔ, a PEGylated Peptidic Erythropoiesis-Stimulating Agent, in RodentsBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 2 2009Kathryn W. Woodburn To support the safety of long-term dosing of chronic renal failure patients, a comprehensive toxicology programme was implemented including rat subchronic and chronic studies. Rats were administered 0, 0.1, 1 and 10 mg/kg of Hematide every 3 weeks for 3 months via subcutaneous injection or for 6 months via intravenous injection. The dosing period was followed by a 6-week follow-up period. The primary pharmacology of Hematide resulted in erythroid polycythemia as measured by elevated haemoglobin levels that were time- and dose-dependent. The pharmacology profiles were similar regardless of administration route. For example, for male rats at Day 90, subcutaneous dosing resulted in haemoglobin increases of 2.7, 4.5 and 6.9 g/dl for 0.1, 1 and 10 mg Hematide/kg respectively, compared to 2.8, 5.7 and 7.4 g/dl increases for intravenous dosing. Histopathological changes were related to the prolonged severe polycythemia induced in normocythemic animals administered an erythropoiesis-stimulating agent. The findings included extramedullary haematopoiesis in the spleen and liver, bone marrow hypercellularity and organ congestion. Microscopic findings were reversible, demonstrating a return towards control findings within 6 weeks following cessation of dosing. Systemic exposures, based on both area under the curve (AUC) and maximum concentration (Cmax), were substantially greater for intravenous than subcutaneous administration. No Hematide-specific antibodies were detected. In conclusion, Hematide is a potent erythropoiesis-stimulating agent, and the studies provide support for the safety of clinical development, including chronic dosing, for the treatment of anaemia associated with chronic renal failure. [source] The effect of age, gender, and body mass index on the pharmacokinetics and pharmacodynamics of vildagliptin in healthy volunteersBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 3 2008Yan-Ling He What is already known about this subject ,,Vildagliptin is a new, potent, and selective inhibitor of DPP-4. ,,The efficacy and safety of vildagliptin in type 2 diabetes has been intensively studied in diverse subject populations. ,,There has been little information published about the pharmacokinetics and pharmacodynamics of vildagliptin. What this study adds ,,No clinically relevant changes in pharmacokinetics or pharmacodynamics were observed between young and elderly, male and female, or high body mass index (BMI) and low BMI subjects. ,,The results suggest that no dose modification is necessary for vildagliptin based on the age, gender, or BMI of a subject. Aims To evaluate the effect of age, gender, and body mass index (BMI) on the pharmacokinetics and pharmacodynamics of vildagliptin. Methods Forty healthy subjects received a single oral dose of 100 mg vildagliptin to assess the effects of age, gender, and BMI on the pharmacokinetics and pharmacodynamics, reflected by the time course of inhibition of DPP-4 activity, of vildagliptin. Results Peak concentration and exposure (AUC(0,,)) of vildagliptin were 17% (90% CI 2, 35%) and 31% (90% CI 18, 45%) higher in elderly vs. young subjects. Renal clearance was reduced by 32% (90% CI 17, 45%) in elderly subjects. The pharmacokinetics of vildagliptin were not significantly influenced by gender or BMI. Inhibition of DPP-4 activity was similar regardless of age, gender, or BMI. Conclusions The pharmacokinetics of a single oral 100 mg dose of vildagliptin were not affected by gender and BMI. Exposure to vildagliptin was higher in elderly patients, but this was not associated with any difference in the effect of DPP-4 inhibition. Based on these results, no vildagliptin dose adjustment is necessary for age, gender, or BMI. [source] Short-term outcome after active perinatal management at 23,25 weeks of gestation.ACTA PAEDIATRICA, Issue 7 2004A study from two Swedish tertiary care centres. Aims: To provide descriptive data on women who delivered at 23,25 wk of gestation, and to relate foetal and neonatal outcomes to maternal factors, obstetric management and the principal reasons for preterm birth. Methods: Medical records of all women who had delivered in two tertiary care centres in 1992,1998 were reviewed. At the two centres, policies of active perinatal and neonatal management were universally applied. Logistic regression models were used to identify prenatal factors associated with survival. Results: Of 197 women who delivered at 23,25 wk, 65% had experienced a previous miscarriage, 15% a previous stillbirth and 12% a neonatal death. The current pregnancy was the result of artificial reproduction in 13% of the women. In 71%, the pregnancy was complicated either by preeclampsia, chorioamnionitis, placental abruption or premature rupture of membranes. Antenatal steroids were given in 63%. Delivery was by caesarean section in 47%. The reasons for preterm birth were idiopathic preterm labour in 36%, premature rupture of membranes in 41% and physician-indicated deliveries in 23% of the mothers. Demographic details, use of antenatal steroids, caesarean section delivery and birthweight differed between mothers depending on the reason for preterm delivery. Of 224 infants, 5% were stillbirths and 63% survived to discharge. On multivariate logistic regression analysis comprising prenatally known variables, reasons for preterm birth were not associated with survival. Advanced gestational duration (OR: 2.43 per wk; 95% CI: 1.59,3.74), administration of any antenatal steroids (OR: 2.21; 95% CI: 1.14,4.28) and intrauterine referral from a peripheral hospital (OR: 2.93; 95% CI: 1.5,5.73) were associated with survival. Conclusions: Women who deliver at 23,25 wk comprise a risk group characterized by a high risk of reproductive failure and pregnancy complications. Survival rates were similar regardless of the reason for preterm birth. Policies of active perinatal management virtually eliminated intrapartum stillbirths. [source] | |||||||||||||||||||||||||||||||