Pentoxifylline improves haemoglobin and interleukin‐6 levels in chronic kidney disease

Aim: To assess whether pentoxifylline improves anaemia of chronic kidney disease (CKD) via suppression of interleukin‐6 (IL‐6) and improved iron mobilization. Background: CKD patients may have elevated IL‐6 and tumour necrosis factor alpha levels. These cytokines can increase hepcidin production, which in turn reduces iron release from macrophages resulting in reduced availability of iron for erythropoiesis. In experimental models, pentoxifylline was shown to reduce IL‐6 expression. Methods: We studied 14 patients with stages 4–5 CKD (glomerular filtration rate <30mL/min per 1.73 m²) due to non‐inflammatory renal diseases. None of the patients had received immunosuppressive or erythropoietin‐stimulating agents or parenteral iron. Patients had weekly blood tests for iron studies and cytokines during a control run‐in period of 3 weeks and during 4 weeks of pentoxifylline treatment. Results: Ten patients (eGFR 23 ± 6 mL/min) completed the study. At the end of the run‐in period average haemoglobin was 111 ± 5 g/L, ferritin 92 ± 26 µg/L, transferrin saturation 15 ± 3% and circulating IL‐6 10.6 ± 3.8 pg/mL. Tumour necrosis factor alpha values were below threshold for detection. Treatment with pentoxifylline reduced circulating IL‐6 (6.6 ± 1.6 pg/mL, P < 0.01), increased transferrin saturation (20 ± 5%, P < 0.003) and decreased serum ferritin (81 ± 25 µg/L, P = NS). Haemoglobin increased after the second week of pentoxifylline, reaching 123 ± 6 g/L by week 4 (P < 0.001). Conclusions: Pentoxifylline reduces circulating IL‐6 and improves haemoglobin in non‐inflammatory moderate to severe CKD. These changes are associated with changes in circulating transferrin saturation and ferritin, suggesting improved iron release. It is hypothesized that pentoxifylline improves iron disposition possibly through modulation of hepcidin.     

Absorption pharmacokinetics of clonidine nasal drops in children

Background:  The α2 agonist clonidine has become a popular drug for premedication in children. Effects and pharmacokinetics after oral, rectal, and intravenous administration are well known. The aim of this study was to investigate the absorption pharmacokinetics of clonidine nasal drops in children.
Methods:  Thirteen ASA I pediatric patients received after induction of anesthesia 4 mcg·kg⁻¹ of clonidine by the nasal route. Blood samples were taken during a 12-h period and plasma levels of clonidine were analyzed by liquid chromatography–mass spectrometry. Data were calculated by a computer-aided curve-fitting program.
Results:  Plasma pharmacokinetics following administration of clonidine nasal drops showed a considerable interindividual variability and absorption was delayed and limited. A total of 95% confidence intervals for maximum plasma concentration and time to achieve maximum plasma concentration were 0.4–0.6 ng·ml⁻¹ and 1.4–3.0 h, respectively.
Conclusions:  Clonidine nasal drops are erratically absorbed from the nasal mucosa and, thus, this mode of drug administration is not recommended for premedication purposes.     

Image Integration-Guided Catheter Ablation of Atrial Fibrillation: A Prospective Randomized Study

Background: Several studies have provided details of left atrial anatomy by means of the image integration techniques, particularly focusing on the atypical patterns of the pulmonary veins.
Objective: To compare, in a prospective, randomized fashion, the conventional method of pulmonary vein disconnection and the image integration-guided approach.
Methods: Two hundred and ninety consecutive patients (290 patients, mean age 55 ± 11 years) with drug-refractory paroxysmal or persistent atrial fibrillation were enrolled in the study and were divided into two treatment groups: group 1 (145 patients) undergoing an imaging integration-guided (CartoMerge TM) ablation; group 2 (145 patients) treated by a conventional radiofrequency catheter ablation procedure. The arrhythmia was refractory to at least two antiarrhythmic drugs (IC, amiodarone).
Results: Electrical disconnection of all identified pulmonary veins was obtained in all patients of both groups. Bidirectional block of the cavotricuspid isthmus was achieved in 34 group 1 patients and in 40 group 2 patients. Left mitral isthmus ablation was attempted in 52 group 1 patients and in 56 group 2 patients. At a mean follow-up of 14 ± 12 months, the atrial fibrillation-free survival rate was significantly higher in group 1 patients compared with group 2 patients (88% vs 69%, P = 0.017). The analysis for the subset of patients with previously ineffective ablation (98 patients: 52 group 1 patients and 46 group 2 patients) showed a significantly lower recurrence rate in group 1 versus group 2 (19% vs 48%, P < 0.01).
Conclusions: Our data indicate a superior efficacy of the image-integration guided catheter ablation of atrial fibrillation over the long term.     

Septo‐optic dysplasia in childhood: the neurological,cognitive and neuro‐ophthalmological perspective

Aim We set out to describe 17 patients with septo‐optic dysplasia (SOD), focusing on the little‐explored neurological, cognitive, and neuro‐ophthalmological components. A further aim was to identify possible clinical correlations and phenotypic characteristics within the diagnostic spectrum. Method We collected clinical‐instrumental data (from the history, general and neurological examination, developmental assessment, and neuro‐ophthalmological, neuroradiological, neurophysiological, and endocrinological evaluations) on nine males and eight females (mean age 34.4mo, SD 31.6; range 4mo‐9y 6mo) diagnosed with SOD who were referred to our Centre of Child Neuro‐ophthalmology between 1999 and 2010. Results We observed a heterogeneous clinical spectrum characterized by nervous system, visual, and endocrine dysfunctions; optic nerve involvement was present in all 17 children, midline brain defects in 14, and cortical developmental malformations in seven. Developmental/cognitive delay and relational and communication difficulties were observed in eight and seven children, respectively, and reduced visual acuity and oculomotor dysfunction were observed in all. Pituitary hormone deficiencies were present in nine children. Interpretation Nervous system involvement emerged as a key feature of SOD. As part of a holistic approach to the disease, particular attention should be paid to this aspect. The emergence of new clinical correlations and correlations between clinical features and three SOD subtypes opens the way for better clarification of this disease and, therefore, more targeted diagnosis, follow‐up, and care of affected children.     

Duration of filgrastim mobilization and apheresis yield of CD34+ progenitor cells and lymphoid subsets in normal donors for allogeneic transplantation

Seventy-seven normal donors underwent leukapheresis for peripheral blood progenitor cell collection beginning on day 4 ( n  = 45) or day 5 ( n  = 32) of filgrastim mobilization (12 μg/kg/d). The two groups were comparable for age, weight, blood volumes processed during leukapheresis and target CD34⁺ cell dose to be collected. The day 5 schedule allowed a more consistent achievement of the target cell dose with one apheresis ( P  = 0.005) and resulted in the initial collection of a significantly larger number of CD34⁺ cells ( P  = 0.009). There was no statistically significant difference in the leukapheresis yield of lymphoid subsets and natural killer cells.