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Low-threshold, persistent sodium current in rat large dorsal root ganglion neurons in culture.

Dorsal root ganglion neurons from adult rats (> or = 200 g) were maintained in culture for between 1 and 3 days. Membrane currents generated by large neurons (50-75 microns apparent diameter) were recorded with the whole cell patch-clamp technique. Large neurons generated transient Na+ currents and at least two types of inward current that persisted throughout 200-ms voltage-clamp steps to +20 mV. One persistent current activated close to -35 mV (high threshold), whereas in about half of the cells another persistent current began to activate negative to -70 mV (low threshold). The high-threshold persistent current was identified as a Ca2+ current, as previously described in these neurons. The low-threshold current was reversibly suppressed either by replacing external Na+ with tetramethylammonium ions or by reducing external Na+ concentration ([Na+]) and simultaneously raising external [Ca2+]. It was blocked by tetrodotoxin (TTX) with an apparent equilibrium dissociation constant in the single nanomolar range. We conclude that the low-threshold current is a TTX-sensitive, persistent Na+ current. The persistent TTX-sensitive current contributed to steady-state membrane current from at least -70 mV to 0 mV, a wider potential range than predicted by activation-inactivation gating overlap for transient Na+ current. Because of its low threshold and fast activation kinetics, the persistent Na+ current is expected to play an important role in determining membrane excitability.

Animals↗

Validation of a short questionnaire in English and French for use in patients with persistent upper gastrointestinal symptoms despite proton pump inhibitor therapy: the PASS (Proton pump inhibitor Acid Suppression Symptom) test.

BACKGROUND: The management of persistent symptoms during acid suppression therapy in patients with gastroesophageal reflux disease or dyspepsia might be improved if patient-physician communication regarding the presence and character of these persistent symptoms were facilitated. AIM: To validate a short, simple questionnaire (the Proton pump inhibitor [PPI] Acid Suppression Symptom [PASS] test), in English and French, to identify patients with persistent acid-related symptoms during PPI therapy and document their response to a change in therapy. METHODS: Patients with persistent acid-related symptoms on PPI therapy were interviewed to produce a draft, five-item questionnaire; content validity was evaluated by focus groups comprising English- and French-speaking patients. Psychometric validity was subsequently evaluated in a multicentre, family practice-based study of English- and French-speaking patients with persistent acid-related upper gastrointestinal symptoms despite PPI therapy. The PASS test, Global Overall Symptom scale, Gastrointestinal Symptom Rating Scale (GSRS), Quality of Life in Reflux and Dyspepsia questionnaire and Reflux Disease Questionnaire were completed at baseline and repeated after one week while patients continued their original PPI therapy. All patients then received esomeprazole 40 mg once daily for four weeks, after which all questionnaires and an evaluation of overall treatment effect were completed. RESULTS: Content validity was established in 20 English- and 16 French-speaking patients. Psychometric validation in 158 English- and 113 French-speaking patients revealed good-to-excellent test-retest reliability coefficients: 0.76 for English; 0.68 for French. For construct validity, the PASS test showed moderate-to-high correlation with the GSRS scale (0.51 for English; 0.43 for French). After four weeks of therapy, the PASS test score fell to zero in 30% of English- and 33% of French-speaking patients, while the Global Overall Symptom score fell to one (no symptoms) in 32% of patients (English- and French-speaking); the PASS test demonstrated good responsiveness in comparison with the GSRS, Reflux Disease Questionnaire and Quality of Life in Reflux and Dyspepsia questionnaire. CONCLUSION: The five-item PASS test is a valid tool for the evaluation of persistent acid-related symptoms in patients receiving PPI therapy. It demonstrates good content validity, test-retest reliability, responsiveness and construct validity in both English and French forms. The PASS test is a simple, clinically applicable tool for the identification of patients with persistent acid-related symptoms during therapy and the assessment of their responses to a change in therapy.

Dyspepsia↗

[Risk factors for the development and persistence of asymptomatic bacteriuria in patients with type 2 diabetes].

BACKGROUND AND OBJECTIVE: To study the risk factors for the development and persistence of asymptomatic bacteriuria (AB) in type 2 diabetes mellitus (DM) patients from our health zone. PATIENTS AND METHOD: Observational and laboratory prospective cohort study. INCLUSION CRITERIA: women and men with type 2 DM from the 2 health centers of Petrer (Alicante). DATA: questionnaire including particular and epidemiological data. Laboratory values: biochemistry, glycosylated hemoglobin A1C, microalbuminuria, urinary sediment and urine culture. RESULTS: A total of 457 patients with type 2 DM were included; 63.2% women and 36.8% men. The prevalence of AB at baseline was 19.9% (25.6% in women vs 10.1% in men). 78.02% had persistence of AB after the twelve months of follow-up; 21.7% developed symptomatic urinary tract infection (UTI) and 35.2% were treated with antimicrobial agents for any reason different from UTI during the follow-up period. The persistence of AB at the end of the study was 15.5%. Female sex (p = 0.04), leukocyturia (p = 0.008), urinary incontinence (p = 0.04) and elevated C reactive protein concentration (p = 0.009) remained significant risk factors for the presence and the persistence of AB when the multivariate logistical regression analysis was done. The presence of UTI within one year before the study started (p= 0.024) and previous antibiotic treatments (p = 0.04) were also independent significant factors associated with persistent AB. 84.5% of diabetic patients with persistent AB had the same infective organism in the urine culture as those found during the initial AB. CONCLUSIONS: In patients with type 2 diabetes, female sex, urinary incontinence, leukocyturia, and elevated C reactive protein concentration were associated with development of AB. The same occurred with obesity in women and prostatic syndrome in men. The persistence of AB with the same species of isolated microorganisms as those found in AB at study entry is frequent, but it remains to be known if eradication of pathogens is more difficult in diabetic patients or, alternatively, if AB episodes are transient.

Aged↗

Persistent detection of alfa-fetoprotein in the vagina without overt preterm premature rupture of the membranes. Clinical and chemical characterizations.

OBJECTIVES: The objectives of this study were to clinically characterize and seek risk factors for the patients with persistently detected alfa-fetoprotein (AFP) in the vagina without showing overt preterm premature rupture of the membranes (PROM). STUDY DESIGN: The cohort study was undertaken using vaginal-cervical specimens collected consecutively between 21 and 40 weeks of gestation from 25 consenting women. Demographic, obstetric, neonatal, and laboratory data from patients with persistent positive results of AFP kit tests without showing overt leakage of amniotic fluid were compared to those from controls. Cervical levels of interleukin-1 alpha, interleukin-1 beta, interleukin-6, interleukin-8, and granulocyte elastase were measured by immunoassay, and the uterine cervix was assessed by transvaginal ultrasonography. Statistical analysis involved Fisher's exact test and Mann-Whitney U test. RESULTS: The incidence of overt preterm PROM was significantly higher in the patients with persistently detected AFP in preterm (3 in 4 cases) than in controls (3 in 21 controls). At sampling before determination of persistently detected AFP, patients with persistently detected AFP had significantly higher cervical levels of interleukin-6 and significantly shorter cervical length than controls. CONCLUSIONS: Patients with persistently detected AFP in the vagina without showing overt preterm PROM have the risk of overt preterm PROM. Increased levels of interleukin-6 in cervical specimens and short cervical length may be risk factors for the occurrence of persistent detection of AFP in the preterm.

Cervix Uteri↗

Factors associated with persistent airflow limitation in severe asthma.

Persistent airflow limitation can develop in nonsmoking patients with asthma. However, the prevalence and risk factors for airways obstruction with incomplete reversibility in asthma are unknown. We assessed the prevalence of persistent airflow limitation (defined as postbronchodilator FEV(1) or FEV(1)/VC < 75% predicted) in 132 nonsmoking outpatients with severe asthma visiting chest physicians in general hospitals in The Netherlands. They had used inhaled corticosteroids (> or = 1,600 microg/d) and/or daily oral prednisone and long-acting bronchodilators for > 1 yr. In addition, we examined whether persistent airways obstruction in these patients was associated with specific clinical characteristics (age at onset, smoking history, atopic status, bronchodilator reversibility, provocative concentration of histamine causing a 20% decrease in FEV(1) [PC(20)histamine]) or markers of inflammation (exhaled nitric oxide [NO], blood eosinophils, total IgE; and eosinophilia or neutrophilia in induced sputum). Multiple logistic regression analyses were used to calculate adjusted odds ratios (OR). Persistent airflow limitation was observed in 49% of the patients in the study, and apart from older age and longer asthma duration, was strongly associated with a sputum eosinophils percent > or = 2% (OR = 7.7; confidence interval [CI]: 2.4 to 25), PC(20)histamine < or = 1.0 mg/ml (OR = 3.9; CI: 1.2 to 13), and adult onset (> or = 18 yr) of asthma (OR = 3.3; CI: 1.2 to 9). Only sputum eosinophilia appeared to be independently associated with persistent airflow limitation (OR = 8.9; CI: 1.3 to 59). In conclusion, persistent airflow limitation is common in adult patients with severe asthma, and is associated with adult onset of the disease, airway hyperresponsiveness, and most importantly, sputum eosinophilia. These findings suggest that eosinophilic airway inflammation contributes to persistent airflow limitation in severe asthma. Whether reduction of sputum eosinophils with more vigorous treatment leads to a better prognosis in severe asthma is still an open question.

Adolescent↗

Microchimerism of maternal origin persists into adult life.

Recent studies indicate that fetal cells persist in maternal blood for decades after pregnancy. Maternal cells are known to engraft and persist in infants with immunodeficiency, but whether maternal cells persist long-term in immunocompetent offspring has not specifically been investigated. We developed sensitive human leukocyte antigen-specific (HLA-specific) PCR assays and targeted nonshared maternal HLA genes to test for persistent maternal microchimerism in subjects with scleroderma and in healthy normal subjects. Nonshared maternal-specific DNA was found in 6 of 9 scleroderma patients. In situ hybridization with double labeling for X and Y chromosome-specific sequences revealed female cells in peripheral blood samples from 2 male scleroderma patients. HLA-specific PCR also frequently revealed persistent maternal microchimerism in healthy control subjects. The mean age of all subjects with maternal microchimerism was 28 years (range: 9-49 years). With few exceptions, mothers of subjects with persistent maternal microchimerism were HLA incompatible with subjects for class I and class II alleles. These results clearly indicate that HLA-disparate maternal cells can persist in immunocompetent offspring well into adult life. The biological significance of maternal microchimerism and whether it might contribute to autoimmune disease requires further investigation.

Adolescent↗

Persistent fungemia--risk factors and outcome in 40 episodes.

The aim of this multicenter survey was to assess risk factors and mortality in patients with persistent fungemia (PF). Cases of persistent fungemia, defined as positive blood culture for at least 3 causative days of antifungal therapy were selected. Forty cases of persistent fungemia (lasting more than 3 days) were compared with 270 non-persistent fungemias appearing within the same period, and analyzed by univariate and multivariate analysis for risk factors and outcome. The median number of days of positive culture was 4.4 (3 - 20): 22 episodes were due to Candida albicans, 1 due to non-albicans Candida spp., 6 episodes due to non-Candida spp. Yeasts: 15 were catheter related, 16 patients had yeast-infected surgical wounds, 12 were neutropenic, 4 cases were caused by species resistant in vitro, 2 to amphotericin B (Trichosporon spp.) and 2 to fluconazole (C. laurentii, C. glabrata). Fifteen patients (37.5%) died, 7 of whom due to fungemia. Nineteen cases had one known risk factor (10 had infected wound, 4 infected vascular catheter, 3 were neutropenic and 2 had inappropriate therapy). Fourteen cases had two known risk factors (4 had wound and infected catheter, 4 neutropenia and infected catheter, 2 neutropenia and resistant organism, 4 other combinations. Two cases had 3 known risk factors and one had 4 risk factors for persistent fungemia. Artificial ventilation, C. glabrata etiology, non-Candida spp. yeasts such as Trichosporon spp. and Cryptococcus spp. and prior surgery were significantly associated with persistent fungemia in univariate, whereas only C. glabrata etiology in multivariate analysis. Breakthrough fungemia during empiric therapy with fluconazole was also observed more frequently in patients with persistent fungemia. However, there was no difference in both attributable and overall mortality between both groups.

Aged↗

Compliance and persistence with bisphosphonate dosing regimens among women with postmenopausal osteoporosis.

OBJECTIVE: Poor compliance and persistence with bisphosphonates is a concern in postmenopausal osteoporosis due to its negative impact on fracture risk and healthcare costs as well as quality of life. Reducing oral bisphosphonate dosing frequency is one measure available to increase therapy convenience and practicality, with the hope of improving compliance and persistence. This study compared compliance and persistence with weekly and daily bisphosphonate regimens for postmenopausal osteoporosis. METHODS: Administrative claims data (1997-2002) from 30 health plans were used to identify postmenopausal women (> 45 years) with osteoporosis, who had been newly prescribed a once-weekly (QW alendronate 35 mg or 70 mg) or once-daily (QD alendronate 5 mg or 10 mg or risedronate 5 mg) bisphosphonate. QW and QD cohorts were followed for 12 months from initial prescription. Medication possession ratios (MPRs) measured refill compliance during follow-up. Persistence was calculated as the number of days from the initial prescription to a lapse of > 30 days after completion of the previous refill. RESULTS: Data were available for 2741 women (QW, N = 731, QD, N = 2010). QW users had significantly higher medication compliance than QD users (69.2% vs. 57.6% MPR, p < or = 0.0001). QW users persisted with therapy significantly longer than QD users (p < 0.0001) and had higher rates of retention on treatment at 12 months than QD users (44.2% QW; 31.7% QD). Dosing frequency was the strongest predictor of time to discontinuation (p < 0.0001). CONCLUSIONS: Postmenopausal women prescribed a weekly bisphosphonate had significantly better compliance and persistence than those taking more frequent, daily bisphosphonate doses. However, compliance and persistence rates for both regimens were suboptimal, suggesting that less frequent dosing intervals may provide an opportunity to further improve the consistent use of bisphosphonate therapy.

Age Factors↗

A scale for measuring persistence in children.

Persistence and its assessment have been studied since the 1920s. One common approach in measuring persistence has been through testing the subject's ability to solve difficult or monotonous problems. Another approach has been through questionnaires. Although persistence is very important in academic achievement and in the general development of personality, no questionnaires have been developed for measuring persistence in children. The present research concerns the development of such a scale. It includes 40 items and was tested on 322 Israeli children aged 7-13. The internal reliability of the scale (Cronbach alpha) was .66, and the test-retest reliability after 6 months was .77. The scale differentiated active gymnasts from non-gymnasts as well as persistent gymnasts from dropout gymnasts. In addition, significant correlations were found between the scale and the need-persistence measure of the Rosenzweig Picture Frustration Study, Locus of Control, and other measures. We discuss these findings along with the significance of persistence in everyday life.

Journal Article↗

Persistent changes in gene expression induced by estrogen and progesterone in the rat mammary gland.

Epidemiological studies have consistently shown that an early full-term pregnancy is protective against breast cancer. We hypothesize that the hormonal milieu that is present during pregnancy results in persistent changes in the pattern of gene expression in the mammary gland, leading to permanent changes in cell fate that determine the subsequent proliferative response of the gland. To investigate this hypothesis, we have used suppression subtractive hybridization to identify genes that are persistently up-regulated in the glands of E- and progesterone (P)-treated Wistar-Furth rats 28 d after steroid hormone treatment compared with age-matched virgins. Using this approach, a number of genes displaying persistent altered expression in response to previous treatment with E and P were identified. Two markers have been characterized in greater detail: RbAp46 and a novel gene that specifies a noncoding RNA (designated G.B7). Both were persistently up-regulated in the lobules of the regressed gland and required previous treatment with both E and P for maximal persistent expression. RbAp46 has been implicated in a number of complexes involving chromatin remodeling, suggesting a mechanism whereby epigenetic factors responsible for persistent changes in gene expression may be related to the determination of cell fate. These results provide the first support at the molecular level for the hypothesis that hormone-induced persistent changes in gene expression are present in the involuted mammary gland.

Animals↗

Effect of education through a periodic newsletter on persistence with antihypertensive therapy.

Sufficient persistence with therapy is important to achieve the desired benefits of antihypertensive therapy. This study was designed to describe the rates of persistence with antihypertensive therapy for 1 year and to assess the effect of patient education by a periodic newsletter on persistence rates in general practice in Japan. Information on 5,324 patients who received the newsletter once a month for 1 year (intervention group; 53.9% of those originally registered) and 666 patients who did not receive the newsletter (control group; 94.3% of those originally registered) was obtained from a physician questionnaire (response rate: 54.3%). The rate of persistence with antihypertensive therapy in the intervention group was similar to that in the control group (91.7% vs. 90.7%, respectively). The patient questionnaire (response rate: 28.2%) indicated that most patients consistently read the newsletter and found it useful in understanding the management of hypertension. The results of this 1-year study showed that about 90% of patients persisted with therapy for 1 year. Although most of them evaluated the newsletter favorably, no clear effect of the newsletter on their persistence with therapy was revealed. However, these results do not rule out a possible effect of education on persistence with therapy over the long-term, and thus there is need of a longer-term study employing follow-up questionnaires.

Aged↗

Persistence with antihypertensives related to formulation: the case of nifedipine.

BACKGROUND: Controlled-release dosage forms may enhance persistence with therapy because of reduced dosing frequency and fewer adverse effects. OBJECTIVE: To assess the differences in persistent use of nifedipine between once-daily nifedipine gastrointestinal therapeutic system (GITS) and twice-daily nifedipine retard formulations. METHODS: Incident nifedipine users were selected from January 1992 to December 2001 from the PHARMO database, including drug-dispensing records and hospital records of more than one million subjects in the Netherlands. Patients with unaltered formulation and dosing frequency of nifedipine in the first year of follow-up with at least 2 prescriptions were included in the cohort. Persistence with different formulations was assessed using Cox's proportional hazard analyses. Covariates included in the analysis were, among others, hospitalizations and comedication for cardiovascular diseases. RESULTS: In total, 5889 incident users of nifedipine were included. The median duration of the first treatment episode was 133 days for nifedipine retard and 262 days for nifedipine GITS. One-year persistence with nifedipine increased from 32% in patients using retard formulations to 44% in patients using nifedipine GITS. Multivariate analyses showed that patients using nifedipine GITS were 1.3 times (RR 1.33; 95% CI 1.22 to 1.46) more persistent than those using retard formulations of nifedipine. Persistent patients more often used other antihypertensive drugs and were more often hospitalized for cardiovascular diseases. CONCLUSIONS: Patients using once-daily nifedipine GITS are more persistent with therapy than patients using twice-daily retard formulations.

Adult↗

Concurrent use of metered-dose and dry powder inhalers by children with persistent asthma does not adversely affect spacer/inhaler technique.

BACKGROUND: Studies conducted in adults have suggested that patients who use a metered-dose inhaler/holding chamber spacer (MDI/S) and dry powder inhaler (DPI) concurrently will have poorer MDI/S technique than that of patients who use MDI/S exclusively. To our knowledge, as of August 31, 2006, no studies have been performed in pediatric patients. OBJECTIVE: To compare MDI/S technique scores of children using only MDI/S with scores of those using both MDI/S and DPIs. METHODS: The MDI/S technique of children aged 6-17 years, with persistent asthma, recruited from a general pediatric practice population for an asthma intervention study project was scored using a standardized checklist. MDI/S scores of children who were being treated with maintenance and rescue medication delivered only by MDI/S were compared with those treated with both MDI/S (rescue) and DPI (maintenance). Scores lower than 70% were considered to be inadequate. RESULTS: A total of 117 patients (73 male, 44 female), aged 9.70 +/- 3.1 years (mean +/- SD), with persistent asthma, participated in the study. There were 83 children (54 male, 29 female, age 9.4 +/- 3.2 y) in the MDI/S only group and 34 (19 male, 15 female, age 10.3 +/- 2.9 y) in the MDI/S + DPI group. In the MDI/S + DPI group, Diskus was the DPI used for 32 patients, and Turbuhaler was used by 2 children. Sixteen patients had severe persistent asthma, 80 had moderate persistent asthma, and 21 had mild persistent asthma as classified by National Heart Lung and Blood Institute guidelines. No difference in sex and age demographics existed; however, there was a difference in the distribution of asthma severity between groups (ie, no patients with mild persistent asthma in the MDI/S + DPI group; p < or = 0.01). Mean score for the MDI/S only group was 86 +/- 17% and, for the MDI/S + DPI group, 90.1 +/- 12% (p = 0.15). More patients in the MDI/S group had inadequate scores (18%) compared with those in the MDI/S + DPI group (3%; p < 0.05). CONCLUSIONS: While DPI and MDI/S techniques are markedly different in several significant ways, concurrent use of these inhalers did not adversely affect MDI/S technique scores of pediatric patients with persistent asthma, compared with those using MDI/S alone. Patients in the MDI/S only group had an inadequate MDI/S score (<70%) more often than did patients in the MDI/S + DPI group.

Administration, Inhalation↗

Correlation between sexual maturation and induction of persistent estrus by continuous illumination.

The rats brought up under continuous illumination from the neonatal day persist in the rhythmic estrous cycle for long time and do not easily reveal so-called continuous vaginal estrus. On the contrary, immature rats at about 30 days of age show the persistent estrus soon after exposure to continuous illumination as well as adult rats. The purpose of this paper was to examine the relation of the age placed under continuous illumination and the time required to reach the persistent estrus. As the results, it was found that the younger rats need proportionally the longer time to reach the persistent estrus; the rats which were transferred into continuously illuminated environment at 0 (group A), 5 (group B), 10 (group C), 15-16 (group D) and 30 (group E) days of age required a mean time of 132.1 +/- 8.4, 126.8 +/- 8.9, 89.7 +/- 6.2, 91.5 +/- 3.8 and 70.3 +/- 3.0 days after birth to reach the persistent estrus, respectively. In the present data, a significant difference was seen between group B and C. Though all rats were killed after the same length of persistently estrous periods, actual endocrine level appeared to differ among the groups; the rats required longer time to reach the persistent estrus had smaller ovaries and adrenals.

Age Factors↗

Does environment mediate earlier onset of the persistent childhood asthma phenotype?

OBJECTIVE: We investigated the role of environmental and hereditary factors in determining whether persistent childhood wheezing phenotypes had an early or late onset. METHODS: In a whole population birth cohort (n = 1456), children were seen at birth and at 1, 2, 4, and 10 years. At each visit, information was collected prospectively regarding wheeze prevalence and used to classify subjects into wheezing phenotypes. Information on genetic and environmental risk factors in early life was also obtained prospectively, and skin-prick testing to common allergens was performed at 4 years. RESULTS: Early-onset persistent wheezers (n = 125) had wheeze onset in the first 4 years, still present at age 10, whereas late-onset persistent wheezers (n = 81) had wheeze onset after age 4 years that was still present at 10 years. Multivariate logistic regression analysis identified independent significance only for inherited factors (parental asthma, family history of rhinitis, eczema at 4 years, and atopic status at 4 years) in the development of late-onset persistent wheeze. However, low social class at birth, recurrent chest infections at 2 years, and parental smoking at 2 years plus inherited factors (eczema at 2 years; food allergy at 4 years; maternal asthma, sibling asthma, maternal urticaria, and atopic status at 4 years) demonstrated independent significance for early-onset persistent wheeze. CONCLUSION: Inheritance seems to be of prime significance in the cause of persistent childhood wheeze. Environmental exposure in early life may combine with this tendency to produce an early onset of persistent wheeze. Absence of these environmental factors might delay but not prevent the onset of wheeze in children with atopic heredity.

Age of Onset↗

Montelukast: a review of its therapeutic potential in persistent asthma.

Montelukast is a cysteinyl leukotriene receptor antagonist used to treat persistent asthma in patients aged > or = 6 years. The drug has a rapid onset of action. Improvements in lung function and reductions in as-needed beta2-agonist usage are apparent within 1 day of initiating montelukast treatment in adults and adolescents (aged > or = 15 years treated with 10 mg/day) or children (aged 6 to 14 years treated with 5 mg/day) with persistent asthma as shown in clinical trials. In two 12-week, multicentre, randomised, double-blind studies in adults and adolescents aged > or = 15 years with persistent asthma [forced expiratory volume in 1 second (FEV1) = 50 to 85% predicted] there was significantly (p < 0.05) greater improvement in FEV1, symptom scores, peak expiratory flow (PEF), as-needed beta2-agonist use, peripheral eosinophil counts and health-related quality of life (QOL) in patients treated with montelukast 10 mg/day than in recipients of placebo. Improvements were significantly greater in patients treated with inhaled beclomethasone 400 microg/day than in recipients of montelukast 10 mg/day in 1 of these studies. Nonetheless, 42% of montelukast recipients experienced > or = 11% improvement in FEV1, the median improvement in this parameter in beclomethasone-treated patients. In an 8-week multicentre, randomised, double-blind, study in children aged 6 to 14 years with persistent asthma (FEV1 50 to 85% predicted), montelukast 5 mg/day produced significantly greater improvements in FEV1, clinic PEF, as-needed beta2-agonist use, peripheral eosinophil counts, asthma exacerbations and QOL scores than placebo. The combination of montelukast 10 mg/day plus inhaled beclomethasone 200 microg twice daily provided significantly better asthma control than inhaled beclomethasone 200 microg twice daily in adults with poorly controlled asthma (mean FEV1 = 72% predicted) despite 4 weeks treatment with inhaled beclomethasone. Patients receiving the combination experienced significant improvements in FEV1 and morning PEF, significant reductions in daytime symptom scores, as-needed beta2 agonist usage and night-time awakenings with asthma, and had significantly lower peripheral blood eosinophil counts after 16 weeks in this multicentre, randomised, double-blind, placebo-controlled study. Among adults (FEV1 > or = 70%) treated with montelukast 10 mg/day for 12 weeks, inhaled corticosteroid dosages were titrated downward by 47% (vs 30% in placebo recipients), 40% of patients were tapered off of inhaled corticosteroids (vs 29%), and significantly fewer patients (16 vs 30%) experienced failed corticosteroid rescues in a multicentre, randomised, double-blind study. During clinical studies, the frequency of adverse events in montelukast-treated adults, adolescents and children was similar to that in placebo recipients. In conclusion, montelukast is well tolerated and effective in adults and children aged > or = 6 years with persistent asthma including those with exercise-induced bronchoconstriction and/or aspirin sensitivity. Furthermore, montelukast has glucocorticoid sparing properties. Hence, montelukast, as monotherapy in patients with mild persistent asthma, or as an adjunct to inhaled corticosteroids is useful across a broad spectrum of patients with persistent asthma.

Acetates↗

[Effect of diabetes mellitus in recovery and maintenance of sinus rhythm in patients with persistent atrial fibrillation].

INTRODUCTION: Diabetes mellitus is frequently accompanied by cardiac rhythm disorders. On the other hand, atrial fibrillation is the most frequent cardiac arrhythmia in adult population [1, 2]. According to some of the large epidemiological studies diabetes mellitus is among independent risk factors for development and persistence of atrial fibrillation [3]. Both diabetes mellitus and atrial fibrillation independently increase the risk of thromboembolism, especially of stroke [3-5]. It is obvious that rhythm control, i.e. restoration and maintenance of sinus rhythm, may be essential for prevention of thromboembolism in these patients. THE AIM OF THE STUDY: The aim of this study is to analyse the impact of diabetes mellitus on rhythm control in patients with persistent atrial fibrillation. METHODS: We analysed the impact of diabetes mellitus and other clinical and echocardiographic parameters (age, gender, current arrhythmia duration, presence of previous episodes of persistent atrial fibrillation, cardiac and/or noncardiac diseases, left atrial diameter and left ventricular ejection fraction) on outcome of attempted cardioversion in patients with persistent atrial fibrillation admitted to Cardiologic Department of the Institute of Cardiovascular Diseases, Clinical Centre of Serbia, between January 1992 and December 1999. We also analysed retrospectively the impact of diabetes mellitus and other parameters listed above on the presence of previous episodes of atrial fibrillation in our patients, that at our opinion reflected the possibilities of sinus rhythm maintenance in these patients. All continuous parameters were expressed as mean value and standard deviation. Statistical significance of differences between variables was examined using Chi-square test. For identification of independent predictors of examined outcomes we used multiple logistic regression model with 95% of confidence interval. Statistical analysis was performed using Statistical Package for Social Sciences (SPSS) programme. RESULTS: Of 378 patients with currently persistent atrial fibrillation, aged mean 53.98 +/- 11.69 years, there were 266 (70.4%) men. Diabetes mellitus was previously diagnosed in 27 (7.1%) patients, cardiac diseases in 223 (59.0%), noncardiac diseases in 47 (12.4%) and 140 (37.0%) patients had "lone" atrial fibrillation. Left atrial enlargement was noted in 224 (59.3%) patients, and reduced left ventricular ejection fraction in 82 (21.7%). Atrial fibrillation lasted 48 hours to 9 years, mean 8.5 +/- 18.14 months before cardioversion. While 43 patients had previous episodes of persistent AF for last 1-30 years, mean 10.5 +/- 7.3,335 patients never experienced AF before. There was a statistically significant difference in percent of diabetic patients (18.6%/43 vs. 5.7%/335, value of Chi-square test = 7.759, p < 0.01) in these two groups. We analysed the impact of diabetes mellitus on outcome of attempted cardioversion and on presence of previous episodes of AF reflecting the success in maintaining sinus rhythm. Multiple logistic regression models for all of 378 patients, with dependent variable being present in previous recurrent atrial fibrillations and independent variables of clinical and echocardiographic parameters as listed, identified diabetes mellitus to be an independent predictor of repeated atrial fibrillations with relative risk of 4.6 (CI 95%). When dependent variable in the same model was outcome of cardioversion (sinus rhythm is restored in 281/378 patients--74%) diabetes mellitus was not among independent predictors of successful cardioversion. DISCUSSION: The relationship between atrial fibrillation and diabetes mellitus is not completely understood, including the impact of known complications of diabetes mellitus on electrophysiological properties of atrial myocardium and development of atrial fibrillation [6]. Besides being the independent risk factor for occurrence of atrial fibrillation, diabetes mellitus, according to our results, appears to influence the possibilities of maintaining sinus rhythm after cardioversion of permanent atrial fibrillation in diabetic patients. We found that patients with diabetes mellitus and persistent atrial fibrillation may be successfully converted to sinus rhythm like any other group of patients, but the presence of diabetes mellitus increases the risk of arrhythmia recurrence for 4.6 times compared to patients without diabetes mellitus. Obviously, diabetic patients need to be treated with more efficacious antiarrhythmics from the very beginning, including amiodarone, which successfully prevents recurrent atrial fibrillation in the majority of patients [7, 8]. CONCLUSION: We concluded that diabetes mellitus independently predicts the presence of recurrent atrial fibrillation but does not influence the possibility of sinus rhythm restoration. The relationship between atrial fibrillation and diabetes mellitus needs further investigation.

Adolescent↗

Use of serologic evaluation for antibodies against bovine viral diarrhea virus for detection of persistently infected calves in beef herds.

OBJECTIVE: To determine whether use of serologic evaluation of a sentinel sample of calves or cows for antibodies against bovine viral diarrhea virus (BVDV) would accurately predict whether an animal persistently infected with BVDV could be detected in beef herds. SAMPLE POPULATION: 27 cow-calf herds in which the status of persistently infected calves was not known and 11 herds known to have persistently infected calves. Procedure-Detection of persistently infected calves was determined through immunohistochemical testing of tissue obtained at necropsy of all calves that died during calving season and skin (ear notch) specimens obtained from all young stock in the fall of 2002. Serum samples were collected from 30 spring-born calves and 10 mature cows. RESULTS: Optimum serologic test performance at time of weaning was detected when 10 calves were evaluated. At least 3 of 10 randomly selected calves were likely to have a titer > 1:1000 against BVDV type I or II in 53% of herds in which a persistently infected calf was detected during that year (sensitivity, 53%). However, at least 3 of 10 randomly selected calves were also likely to have a titer > 1:1000 in 20% of herds that did not have a persistently infected calf detected during that year (specificity, 80%). CONCLUSIONS AND CLINICAL RELEVANCE: Despite the use of a number of various cutoff values and sample sizes, serologic evaluation of a small number of calves or cows could not be used to accurately predict the presence of persistently infected cattle in a herd.

Animals↗