Comparison of the efficacy and safety of ciclesonide 160 μg once daily vs. budesonide 400 μg once daily in children with asthma

Ciclesonide is an onsite-activated inhaled corticosteroid (ICS) for the treatment of asthma. This study compared the efficacy, safety and effect on quality of life (QOL) of ciclesonide 160 microg (ex-actuator; nominal dose 200 microg) vs. budesonide 400 microg (nominal dose) in children with asthma. Six hundred and twenty-one children (aged 6-11 yr) with asthma were randomized to receive ciclesonide 160 microg (ex-actuator) once daily (via hydrofluoroalkane metered-dose inhaler and AeroChamber Plus spacer) or budesonide 400 microg once daily (via Turbohaler) both given in the evening for 12 wk. The primary efficacy end-point was change in forced expiratory volume in 1 s (FEV1). Additional measurements included change in daily peak expiratory flow (PEF), change in asthma symptom score sum, change in use of rescue medication, paediatric and caregiver asthma QOL questionnaire [PAQLQ(S) and PACQLQ, respectively] scores, change in body height assessed by stadiometry, change in 24-h urinary cortisol adjusted for creatinine and adverse events. Both ciclesonide and budesonide increased FEV1, morning PEF and PAQLQ(S) and PACQLQ scores, and improved asthma symptom score sums and the need for rescue medication after 12 wk vs. baseline. The non-inferiority of ciclesonide vs. budesonide was demonstrated for the change in FEV1 (95% confidence interval: -75, 10 ml, p = 0.0009, one-sided non-inferiority, per-protocol). In addition, ciclesonide and budesonide showed similar efficacy in improving asthma symptoms, morning PEF, use of rescue medication and QOL. Ciclesonide was superior to budesonide with regard to increases in body height (p = 0.003, two-sided). The effect on the hypothalamic-pituitary-adrenal axis was significantly different in favor of ciclesonide treatment (p < 0.001, one-sided). Both ciclesonide and budesonide were well tolerated. Ciclesonide 160 microg once daily and budesonide 400 microg once daily were effective in children with asthma. In addition, in children treated with ciclesonide there was significantly less reduction in body height and suppression of 24-h urinary cortisol excretion compared with children treated with budesonide after 12 wk.     

Nephrology and renal replacement therapy in Romania--transition still continues (Cinderella story revisited).

INTRODUCTION. This report describes the current status of nephrology and renal replacement therapy (RRT) in Romania, a country with previously limited facilities, highlighting national changes in the European context. METHODS: Trends in RRT development were analysed in 2003, on a national basis, using the same questionnaires as in previous surveys (1991, 1995). Survival data and prognostic risk factors were calculated retrospectively from a large representative sample of 2284 patients starting RRT between January 1, 1995 and December 31, 2001 (44% of the total RRT population investigated). RESULTS: In 2003, RRT incidence [128 per million population (p.m.p.)] and prevalence (250 p.m.p.) were six and five times higher, respectively, than in 1995. The annual rate of increase in the stock of RRT patients (11%) was supported mainly by an exponential development of the continuous ambulatory peritoneal dialysis (CAPD) population (+600%), while the haemodialysis (HD) growth rate was stable (+33%) and renal transplantation made a marginal contribution. Renal care infrastructure followed the same trend: nephrology departments (+100%) and nephrologists (+205%). The characteristics of RRT incident patients changed accordingly to current European epidemiology (increasing age and prevalence of diabetes and nephroangiosclerosis). The estimated overall survival of RRT patients in Romania was 90.6% at 1 year [confidence interval (CI) 89.4-91.8] and 62.2% at 5 years (CI 59.4-65.0). Patients' survival was negatively influenced (Cox regression analysis) by age >65 years (P < 0.001), lack of pre-dialysis monitoring by a nephrologist [P = 0.01, hazards ratio (HR) = 0.8], severe anaemia, lack of erythropoetin treatment (P < 0.001, HR = 0.6), and co-morbidity, e.g. cardiovascular diseases (P < 0.001, HR = 1.8) and diabetes mellitus (P < 0.001, HR = 2.2). CONCLUSIONS: Although the rate of increase in RRT patient stock in 1996-2003 in Romania was the highest in Europe, the prevalence remained below the European mean. As CAPD had the greatest expansion, followed by HD, an effective transplantation programme must be set up to overcome the imbalance. The quality of RRT appears to be good and survival was similar to that in other registries. Further evolution implies strategies of prevention, based on national surveys, supported by the Romanian Renal Registry.     

Intravitreal bevacizumab in aggressive posterior retinopathy of prematurity.

The anatomic response to intravitreal bevacizumab injection in three patients with aggressive, posterior retinopathy of prematurity is described. In all cases, the worse eye was treated with a single intravitreal injection of 0.75 mg of bevacizumab as monotherapy or complementary to laser therapy. In 24 hours, all injected eyes showed regression of the tunica vasculosa lentis and iris vessel engorgement and disappearance of iris rigidity. In addition, plus disease and retinal proliferation began to regress. None of the eyes required additional treatment. Follow-up of up to 10 months     

Effects of stimulation and blockade of dopamine receptor subtypes on the discriminative stimulus properties of cocaine

The involvement of dopamine (DA) receptor subtypes in the behavioral effects of CNS stimulants was studied in rats trained to discriminate occaine from saline. In substitution tests, the stimulus effects of 10mg/kg of this substance generalized tod-amphetamine (0.25–1.0 mg/kg) and the selective D₂ against LY-171555 (0.05–0.25 mg/kg); but not to the D₁ agonist SKF-38393 (5.0–15.0 mg/kg); in combination tests, the D₁ antagonist Sch-23390 (0.0625–0.5 mg/kg) significantly blocked, and the D₂ antagonist spiperone (0.25–0.5 mg/kg) partially blocked the cocaine cue. These data suggest that the involvement of DA systems in the behavioral effects of cocaine is more complex than either D₁ or D₂ receptor activation; for example, the stimulus properties of this substance might involve both D₁ and D₂ receptor activation.Some of these results were presented at the meeting of the Society for Neuroscience, Toronto, 1988     

Inadequate dietary magnesium intake increases atherosclerotic plaque development in rabbits

Epidemiological studies have shown dietary magnesium (Mg) intake and serum Mg levels to be inversely correlated with the development of atherosclerosis. We hypothesized that low levels of Mg would promote atherosclerotic plaque development in rabbits. New Zealand white rabbits (4 months old, n = 22) were fed an atherogenic diet containing 0.12% (−Mg), 0.27% (control), or 0.43% (+Mg) Mg for 8 weeks. Blood samples were obtained at baseline, 2, 4, 6, and 8 weeks and were assayed for total cholesterol, high-density lipoprotein (HDL), non-HDL, triglycerides (TG), C-reactive protein, serum Mg, and erythrocyte Mg. Aortas from −Mg had significantly more plaque, with an intima thickness 42% greater than control and 36% greater than +Mg. Serum cholesterol levels rose over time, and at 8 weeks, −Mg had the highest and +Mg the lowest total and non-HDL cholesterol and TG levels, although these results did not reach significance. Over time, serum Mg levels increased, and erythrocyte Mg levels decreased. C-reactive protein significantly increased in all groups at 4 and 6 weeks but returned to baseline levels by 8 weeks. This study supports the hypothesis that inadequate intake of Mg results in an increase in atherosclerotic plaque development in rabbits.     

Pain and faulty breathing: a pilot study

The purpose of this pilot study was to observe both relaxed and deep breathing patterns in a convenience sample to determine the incidence of normal versus faulty patterns of respiration. These observations were then combined with respondent answers to a survey on pain history to determine if there is any correlation between faulty breathing and musculo-skeletal pain patterns. If such a correlation can be made, then we propose that clinicians working with chronic pain patients may have improved outcomes if they address and correct faulty breathing patterns. Based on this study, it is suggested to include the evaluation and treatment of faulty respiration in the rehabilitation of chronic musculo-skeletal conditions, most notably cervical pain.     

Pulmonary delivery of growth hormone using dry powders and visualization of its local fate in rats.

A dry powder aerosol formed of human growth hormone (hGH), lactose and dipalmitoylphosphatidylcholine was assessed for systemic delivery of the hormone in rats. The fate of the protein locally in the deep lung was examined post-delivery. The powder was prepared by spray-drying and presented a primary particle diameter of 4.4 microm and a tap density of 0.069 g/cm(3). The mass median aerodynamic diameter was 4.4 micron in the multi-stage liquid impinger at 60 l/min using a Spinhaler device. The emitted dose and fine particle fraction were 89% and 58%, respectively. Varying the airflow rate from 30 to 90 l/min had limited impact on aerosolization properties in vitro. No hGH dimers or glycation adducts were produced during formulation of the powder. hGH absorbed into the bloodstream with a time to peak of 23 and 52 min and with an absolute bioavailability of 23% and 8% following intratracheal insufflation of the dry powder and intratracheal spray-instillation of a solution of the hormone, respectively. Confocal imaging of rat lung revealed an intense uptake of fluorescein isothiocyanate (FITC)-hGH by alveolar macrophages as early as 1 h post-delivery. A dry powder aerosol made of selected GRAS excipients improved absorption of hGH from the lung over a simple solution.     

Prevalence, clinical characteristics, quality of life, and prognosis of patients with congestive heart failure and isolated left ventricular diastolic dysfunction.

Prevalence of isolated left ventricular (LV) diastolic dysfunction has been reported to be as high as one-third of all heart failure (HF) cases, with an increasing prevalence in the elderly population. However, there is a paucity of prospective data about the prevalence and prognosis of isolated LV diastolic dysfunction in an unselected population of patients hospitalized with HF. Therefore, we prospectively evaluated 179 consecutive patients discharged from our hospital with HF to assess the prevalence of systolic versus diastolic LV dysfunction among patients hospitalized with HF and to compare their demographics, clinical features, self-perceived quality of life (QOL), and 6-month readmission rate and mortality. Among them, 133 (59% men, median age 74 years) showed in sinus rhythm and had no significant primary valvular disease. LV diastolic dysfunction was diagnosed on the basis of the European Study Group on Diastolic HF echocardiographic criteria. QOL was assessed at hospital discharge and 6-month follow-up visit using the Minnesota Living with HF questionnaire. Survival of patients with HF was compared with that of age- and sex-matched general population. In all, 29 patients (22%) had isolated LV diastolic dysfunction and 102 (78%) had prevalent LV systolic dysfunction (ie, LV ejection fraction 相似文献   

Expression of the T-cell markers CD2 and CD28 in healthy and atopic children during the first 18 months of life

Atopy may be associated with a reduced T-cell function early in life, particularly regarding maturation of Th1 responses. The T-cell surface molecules CD2 and CD28 are involved in important T-cell activation pathways. Stimulation via the CD2 receptor increases the responsiveness to interleukin (IL)-12, which is a potent inducer of Th1 responses, whereas CD28 stimulation is critical for Th2 differentiation. Our aim was to prospectively study the expression of the cell-surface markers CD2 and CD28 on T-cells in relation to development of atopic disease. Children (n = 172) were followed from birth to 18 months and the cumulative history of atopic disease was recorded. Blood samples were obtained at birth and at 18 months, and in a subgroup of 78 infants also at 3, 6 and 12 months. Flow cytometry was used to analyze the T-cell markers CD2 and CD28, the latter also within the subsets of T-helper (CD4+) and T-cytotoxic (CD8+) cells. At 18 months, 31 children had and 118 did not have atopic symptoms. At this age, skin prick test (SPT) positive children with atopic symptoms with or without an atopic family history (AFH) showed a lower expression of CD2 mode fluorescence intensity (FI) as well as a lower proportion of CD2+ cells, as compared with non-sensitized children with neither atopic symptoms nor AFH. This was accompanied by a higher expression of CD28 FI on CD2+CD8+CD28+ cells. No significant differences were seen at time points before 18 months, although the proportion of CD2+ tended to be low also earlier in life. In conclusion, the observed reduced expression of CD2 in atopic infants may support previous findings that atopy is associated with a reduced CD2 function. The high CD28 FI in SPT positive children with atopic symptoms may possibly be a consequence of a TH2-skewed immune system.     

The Ab-Adductometer: a new device for measuring the muscle strength and function of the thumb.

The purpose of this study was to present normative values for thumb abduction and adduction and also to present measures of reliability of the measuring system arising from the use of the Ab-Adductometer. With the Ab-Adductometer, we obtained abductor and adductor measurements of intrinsic muscle strength of the healthy hand thumb in 600 volunteers. Handgrip strength values were obtained with the Jamar dynamometer. Age and male-female specific reference ranges for the Ab-Adductometer and the Jamar dynamometer are presented. This study, with a very large number of volunteer subjects, 600, presents reference ranges for pure palmar adduction and abduction of the thumb. The results indicate that the Ab-Adductometer is a clinically useful device for the purpose of quantitatively measuring thumb adduction and abduction strength at various starting angles of thumb abduction relative to the plane of the palm. The device may be especially helpful in the evaluation of compressive neuropathies of the median or ulnar nerves such as carpal tunnel syndrome or cubital tunnel syndrome as well as for primary disease of the peripheral nerves that affect intrinsic muscles and for thumb function in proximal conditions such as tetraplegia and brachial plexopathy.