A new antisense oligonucleotide delivery system based on self-assembled ODN-PEG hybrid conjugate micelles.

The conjugate of antisense c-raf oligonucleotide (ODN) and poly(ethylene glycol) (PEG) was synthesized for intracellular ODN delivery. When combined with polyethylenimine (PEI), the ODN-PEG conjugate self-associated to form polyelectrolyte complex micelles in aqueous solution. The effective hydrodynamic diameter of the micelles was ca. 70 nm with a narrow size distribution. Flow cytometry analysis indicated that the cellular uptake of the micelles by A2780 cells was much higher than that of ODN alone. The micelles also showed a superior antiproliferative activity against ovarian cancer cells in vitro and in vivo.     

Quantitative assessment of variables that influence soft-tissue electrovaporization in a fluid environment

Objectives. To evaluate the process of soft-tissue electrovaporization and to study variables that affect tissue clearance rates in a laboratory setting, in order to identify parameters that can optimize transurethral electrovaporization of the prostate.Methods. Fresh bovine skeletal muscle, equivalent in impedance and surface properties to the human prostate, was submerged in 3.3% sorbitol solution and electrovaporized with a grooved monopolar electrode attached to the weighted arm of a linear actuator. The effects of excursion rate, applied mechanical load, power setting, electrode configuration, and generator performance on the volume of tissue removed, were assessed.Results. Tissue removal increased significantly when electrode excursion rate was slowed from 25 to 15 mm/s (P <0.05) and then to 10 mm/s (P <0.05); when the load was increased from 20 to 50 g (P <0.005); and when dial power was increased from 120 to 150 W (P <0.01). Tissue removal was generator dependent. There was no significant difference between the Force 40 and the Force 2 (P > 0.4), but a new computer-controlled constant power output generator (Force FX) did significantly improve tissue vaporization at an equivalent power setting (P <0.005 and P <0.01, respectively). Tissue removal was also dependent upon electrode configuration, with the VaporTrode-Grooved Bar removing significantly more tissue than either an ungrooved roller bar of equivalent size or 2-mm smooth roller ball, respectively, both after a single pass (P <0.001 and P <0.05) and after five repeated passes (P <0.05 and P <0.005). The histologic depth of tissue thermal effect was less than 1 mm, but it was 38% greater for the VaporTrode-Grooved Bar (0.68 mm) than for the standard cutting loop (0.5 mm, P <0.01).Conclusions. Using a novel method to quantify tissue removal, we have demonstrated that electrode configuration, excursion rate, applied load, power setting, and generator performance are interdependent factors that influence the efficacy of the electrovaporization process in a fluid environment.     

Determinant attributes in formulation of attitudes toward four health care systems.

Consumers were surveyed to determine their attitudes toward four systems of health care delivery (home health care, hospitals, nursing homes, and outpatient clinics) along 10 attributes. The results are analyzed using multiple discriminant analysis. Implications for the formulation of marketing strategies are discussed.     

Increase in brain cerebrospinal fluid volume is greater in older than in younger alcoholic patients: A replication study and CT/MRI comparison

This cross-sectional study used a semi-automated analysis technique to quantify regional brain cerebrospinal fluid (CSF) volumes derived from computed tomography (CT) in 84 healthy men ranging from 21 to 82 years of age and 28 patients meeting Research Diagnostic Criteria for alcohol dependence. The goals were to replicate an earlier CT study of an independent sample of alcoholic and control subjects (Pfefferbaum et al., 1988a; Zipursky et al., 1988) and to compare CT assessments of brain changes with magnetic resonance imaging (MRI) assessments made in the same alcoholic patients (Pfefferbaum et al., 1992). Regional brain changes associated with normal aging were derived by regression analysis, using CT data collected from the healthy control subjects. As in the earlier CT study and in the concurrent MRI study, ventricular and sulcal CSF volumes in alcoholic patients were greater than would be expected for their age. Furthermore, the present CT study replicated the previous CT and MRI findings of a positive relationship between age and CSF volume enlargement in alcoholic patients over and above the normal age-related increase in CSF volume, suggesting greater vulnerability of the aging brain to alcohol. Comparison of CT-and MRI-derived estimates of ventricular and cortical sulcal volume revealed high correlations (>0.80). MRI and CT produced similar absolute ventricular volumes, while MRI produced larger sulcal volume estimates than did CT. The difference in sulcal volume estimate may be due to differences between CT and MRI in slice thickness and sensitivity to partial volume effects.     

HELLP Syndrome: an Often Unrecognized Complication of Preeclampsia

We describe a case of preeclampsia with the HELLP (Haemolysis, Elevated Liver enzymes, Low Platelets) syndrome and highlight the delayed diagnosis due to its nonspecific presentation. This syndrome is associated with significant maternal and perinatal mortality and morbidity and we discuss the importance of early recognition of the condition, aggressive management and a multidisciplinary approach.     

Statistical MUNE: A comparison of two methods of setting recording windows in healthy subjects and ALS patients

OBJECTIVE: To address the issue as to how best to perform statistical MUNE, we applied two different approaches and compared results in healthy subjects and ALS patients. METHODS: Twelve normal subjects (women 8, mean age 52years) and 11 ALS patients (women 4, mean age 54years) underwent two consecutive MUNE studies, which differed in terms of setting and modifying the recording window. These are referred to as the 'expansion' and 'narrowing' methods, respectively. Size-weighted average (Av) SMUP and MUNE values were obtained using the two methods, and compared in control and patient groups. RESULTS: Expansion method-derived Av SMUP sizes and MUNE values differed only slightly from those obtained using the narrowing method in healthy subjects, whereas the narrowing method resulted in significantly larger Av SMUP sizes and smaller MUNE values than the expansion method in ALS patients (Wilcoxon signed ranks test, p=0.003). The sizes of tested areas (mean+/-SD) were significantly larger for the narrowing method than the expansion method in both subject groups with much greater difference in ALS patients; 9.6+/-3.1% vs. 7.9+/-1.7% in healthy subjects and 16.1+/-5.1% vs. 11.2+/-3.0% in ALS patients (Student t-test, p<0.01). CONCLUSIONS: The present study shows, unlike that found in normal subjects, that the results of statistical MUNE in ALS patients are heavily dependent on the approach used to set and modify recording windows. SIGNIFICANCE: The expansion method using a 10%-sized window is likely to suffer from systemic errors due to the ceiling effect and the sampling of artifactually small motor units in ALS patients. The authors recommend that the narrowing method be considered as an alternative that avoids these problems.     

Akinetic Mutism and Cognitive-Affective Syndrome Caused by Unilateral PICA Infarction

A 42-year-old man with left posterior inferior cerebellar artery (PICA) infarction presented with akinetic mutism and cognitive impairment. Initially he suffered from akinetic mutism and MRI-documented infarction in the distribution of the left PICA. Twelve days later he developed cognitive impairment. Neuropsychological tests were performed, with the results corrected for age and education being compared with published Korean norms. Impaired performances were evident on executive function testing, with difficulties in planning, abstract reasoning, set-shifting, and perseveration. Akinetic mutism and cognitive-affective syndrome may be a manifestation of unilateral PICA infarction.