Freeze-drying of itraconazole-loaded nanosphere suspensions: a feasibility study

The present study concerns the stabilization of the association of the new hydrophobic triazole derivative itraconazole within poly-ϵ-caprolactone-nanospheres by means of freeze-drying. We have investigated the freeze-drying of nanospheres, and especially the cryopreservation conditions, with the help of differential scanning calorimetry and zeta potential measurements. Five commonly used cryoprotective agents were evaluated (glucose, sucrose, trehalose, dextran, mannitol at 0, 5, 10, 20, and 30% [w/v]) after freeze-thawing and freeze-drying. The addition of carbohydrates led to a partial protection of the colloidal suspension, with leakage of 30% of itraconazole under the best cryopreservation conditions (10% of glucose or sucrose). Zeta potential measurements revealed that the main destabilization mechanism during freeze-drying was surface modifications of the nanospheres, and particularly drug desorption. Therefore, the hydrophilic surfactant adsorbed at the surface of the nanospheres played an important role in the cryopreservation. Replacing the commonly used non ionic surfactant PLURONIC®PE F68 by the anionic surfactant sodium deoxycholate resulted in a complete stabilization of itraconazole-loaded nanospheres after freeze-drying, with no drug desorption, in the presence of 10% sucrose, but not in the presence of glucose. As shown by thermal analysis, PLURONIC®PE F68 may crystallize during freezing, which could lead to surface modifications and drug desorption, whereas sodium deoxycholate may not. Moreover, the Tg′ of glucose-containing suspensions is 10°C lower than Tg′ of sucrose-containing suspensions, which may explain the shrinkage of the cake observed in the case of glucose and the homogeneous appearance of the dried product in the case of sucrose. © 1996 Wiley-Liss, Inc.     

Antinuclear antibodies in children: clinical signification and diagnosis utility

Background: Antinuclear antibodies (ANA) test is used to screen adults as well as children for connective tissue diseases (CTD) and autoimmune hepatitis. However, interpretation of ANA positivity can be delicate. Aim: to determine clinical significance and diagnosis utility of ANA positivity in children. Methods: Patients from a general pediatric department with ANA positive results were included (follow-up period of 2 years). ANA screening was performed by indirect immunofluorescence (IIF) on HEp-2 cells substrate (BioSystems^®). In case of ANA positivity (cut-off: 1:80), the specificity was determined by IIF on Crithidia luciliea substrate (BioSystems^®) and immunodot (Euroimmun^®). Results: Among 102 ANA tests, 55 (53,9%) were positive. We recorded the data of 38 patients (age average: 9,5 years - sex ratio: 0.72). The most frequent signs were join pain (55,3%). ANA titer varied between 1:80 (39,5% of cases) and 1:1280 (2,6% of cases). Typing was negative in 89,5% of cases. The majority (42,1%) of children with positive ANA test had musculoskeletal diseases. The others (57,9%) had systemic lupus erythematosus(n=2), overlap syndrome(n=1), rheumatoid purpura(n=2), idiopathic thrombocytopenic purpura(n=1), coeliac disease(n=1) or non-autoimmune diseases/no confirmed diagnosis(n=15). Conclusions: ANA prevalence in children was relatively high. When the pretest probability is low, the positive predictive value for CTD or autoimmune hepatitis is low. However, depending on the clinical context, ANA detection can represent a supplement diagnostic tool for these diseases and/or can lead to a clinico-biological monitoring.     

Diagnostic accuracy of myocardial perfusion imaging with single photon emission computed tomography and positron emission tomography: a comparison with coronary angiography

Objective The aim of this study was to compare the diagnostic accuracy of myocardial perfusion imaging (MPI) by positron emission tomography (PET) with the diagnostic accuracy of MPI by single photon emission computed tomography (SPECT) in two comparable patient cohorts, using coronary angiography (CA) as the standard of reference. Methods A “SPECT-group” of 80 patients (15 female, 65 male; mean age 60 ± 9 years) and a “PET-group” of 70 patients (14 female, 56 male; mean age 57 ± 10 years) underwent a one day stress/rest examination either with attenuation-corrected ¹³N-ammonia PET or attenuation-corrected ²⁰¹TlCl SPECT or ^99mTc-hexakis-methoxy-isobutyl-isonitril (MIBI) SPECT. PET and SPECT results were semiquantitatively graded using a 6-segment heart model. All patients underwent CA, and stenoses were graded as a diameter reduction ≥50%. Results Coronary findings between both groups did not significantly differ at CA. For the SPECT-group overall sensitivity and specificity for localisation of stenoses was 77% and 84%. Respective values for the PET-group were 97% and 84%. The specificity of MPI by SPECT in the detection of ischemia was 74% and 91% for MPI by PET. The diagnostic accuracy of MPI improves when the individual coronary dominance and previous coronary revascularisations are taken into account. Conclusion MPI by ¹³N-ammonia PET is more sensitive in the detection and localisation of coronary stenoses, and more specific in the detection of ischemia than MPI by ²⁰¹TlCl/^99mMIBI SPECT.     

Accuracy of dual-source CT coronary angiography: first experience in a high pre-test probability population without heart rate control

The aim of this study was to assess the diagnostic accuracy of dual-source computed tomography (DSCT) for evaluation of coronary artery disease (CAD) in a population with extensive coronary calcifications without heart rate control. Thirty patients (24 male, 6 female, mean age 63.1±11.3 years) with a high pre-test probability of CAD underwent DSCT coronary angiography and invasive coronary angiography (ICA) within 14±9 days. No beta-blockers were administered prior to the scan. Two readers independently assessed image quality of all coronary segments with a diameter ≥1.5 mm using a four-point score (1: excellent to 4: not assessable) and qualitatively assessed significant stenoses as narrowing of the luminal diameter >50%. Causes of false-positive (FP) and false-negative (FN) ratings were assigned to calcifications or motion artifacts. ICA was considered the standard of reference. Mean body mass index was 28.3±3.9 kg/m² (range 22.4–36.3 kg/m²), mean heart rate during CT was 70.3±14.2 bpm (range 47–102 bpm), and mean Agatston score was 821±904 (range 0–3,110). Image quality was diagnostic (scores 1–3) in 98.6% (414/420) of segments (mean image quality score 1.68±0.75); six segments in three patients were considered not assessable (1.4%). DSCT correctly identified 54 of 56 significant coronary stenoses. Severe calcifications accounted for false ratings in nine segments (eight FP/one FN) and motion artifacts in two segments (one FP/one FN). Overall sensitivity, specificity, positive and negative predictive value for evaluating CAD were 96.4, 97.5, 85.7, and 99.4%, respectively. First experience indicates that DSCT coronary angiography provides high diagnostic accuracy for assessment of CAD in a high pre-test probability population with extensive coronary calcifications and without heart rate control.