Improved formulations of antisense oligodeoxynucleotides using wrapped liposomes.

Previously, we demonstrated that wrapping dextran fluorescein anionic/cationic lipid complexes with neutral lipids produced a stable formulation that markedly increased the duration of the compound in plasma after intravenous administration to rats. The improved drug-delivery properties of the wrapped liposomes (WL) relative to other formulations suggested that this technology could offer important advantages for the administration of other polyanionic drugs, including antisense oligodeoxynucleotides (ODN). In the present study, we investigated the value of WL for formulating fluorescence-labeled phosphorothioated ODN (F-ODN). WL encapsulating F-ODN/cationic lipid complexes were prepared efficiently using similar methodology to that used in our earlier study. Studies confirmed that these WL were stable in vitro. Following intravenous administration to mice, free F-ODN and naked F-ODN/cationic lipid complexes were rapidly eliminated whereas administration of the WL resulted in high blood concentrations of drug that were maintained for several hours. Additional studies were conducted in mice that were inoculated with tumor cells (Caki-1 xenograft model, human kidney); in these experiments, intravenous administration of WL delivered 13 times more F-ODN to the tumor site than achieved after injection of free F-ODN.     

Solitary bronchioloalveolar carcinoma: CT criteria

The computed tomographic (CT) scans of 30 patients with solitary bronchioloalveolar carcinoma were reviewed. Common features at CT included the peripheral or subpleural location of a pulmonary mass (25 cases), pseudocavitation (18 cases), heterogeneous attenuation (17 cases), irregular margins forming a star pattern (22 cases), and pleural tags (21 cases). Using these CT criteria, four independent observers attempted to identify cases of bronchioloalveolar carcinoma from a larger sample of lung cancers and benign lesions by categorizing a series of test cases into four probability categories. Although the bronchioloalveolar carcinomas were correctly ranked in the two highest probability categories 75% of the time (in 45 of 60 cases), there was considerable overlap with other lung lesions, particularly with adenocarcinoma and large cell undifferentiated carcinoma. However, even though the typical features of bronchioloalveolar carcinoma are not invariable or highly specific, they are characteristic enough to suggest the diagnosis.     

Stable Anticonvulsant Action of Benzodiazepines During Development in Rats

Abstract— The anticonvulsant action of midazolam and clonazepam was studied in 168 immature rats in three age groups (12, 18 and 25 days old). Epileptic after-discharges of the spike-and-wave type accompanied by clonic seizures of facial and forelimb muscles induced by stimulation of sensorimotor cortex were used as a model. The solvent used for clonazepam exhibited a tendency to anticonvulsant action in 12-day-old rats. On the contrary, a proconvulsant action was seen in 25-day-old animals. The action of both benzodiazepines was identical and did not change substantially during development. The highest dose used (1 mg kg^?1, i.p.) shortened the duration of epileptic after-discharges, the two lower doses (0·1 and 0·02 mg kg^?1, i.p.) suppressed the progressive prolongation with repeated stimulations seen under control conditions. Motor correlates of stimulation remained practically uninfluenced by the two benzodiazepines, myoclonic seizures accompanying epileptic after-discharges were attenuated by the highest dose of both drugs.     

Septo-optic dysplasia: MR imaging

Septo-optic dysplasia is the diagnosis when optic nerve hypoplasia is seen in conjunction with dysgenesis of the septum pellucidum. Nearly two-thirds of these patients have hypothalamic-pituitary dysfunction, and half have schizencephaly. The disorder is difficult to classify because of the diversity of clinical and pathologic manifestations. Magnetic resonance images of 11 patients with clinical and radiographic evidence of septo-optic dysplasia were reviewed retrospectively. The "syndrome" appears to include two subsets of patients whose abnormalities have different embryogenesis and neuropathologic findings. The existence of these two subsets helps to explain the diversity of the clinical and radiologic findings.     

Effectiveness of the bidirectional Glenn shunt for the univentricular heart

Two cases underwent a modified Fontan operation with simultaneous superior vena cava-right pulmonary artery end-to-side anastomosis, which we called "bidirectional Glenn shunt". This anastomosis seems to be so effective for reduction of right arterial volume loading, and could proved life-saving in the case with the acute obstruction at the site of the right atriopulmonary artery anastomosis immediately after surgery.