Inhibition of Human Mammary Cell Line Proliferation by Membrane Lectin-Mediated Uptake of Ha-ras Antisense Oligodeoxynucleotide

The Ha-ras oncogene promotes cell proliferation. Antisense oligonucleotides complementary to the ras gene sequence encompassing a mutated codon 12 selectively induce a cell proliferation inhibition. However, the concentration required to reach an effective inhibition is high due to the low efficiency of the oligonucleotide crossing through cell membranes, leading to a low concentration in the cytosol and/or the nucleoplasm. In the present paper, we show that anti-ras oligonucleotides linked to a glycosylated carrier, serum albumin bearing mannose 6-phosphate residues, are more efficient than free oligonucleotides or oligonucleotides bound to an unglycosylated carrier at inhibiting proliferation of a human tumor mammary cell line expressing the mutated Ha-ras. Using fluorescein-labeled neoglycoproteins and fluorescein-labeled oligonucleotides bound to neoglycoproteins, flow cytometry and confocal microscopy revealed that (i) these tumor cells express a membrane lectin specific for mannose 6-phosphate-bearing proteins, (ii) the membrane lectin actively mediates the uptake of macromolecules substituted with mannose 6-phosphate, and (iii) the fluorescein-labeled oligonucleotides bound to the neoglycoprotein accumulate in intracellular vesicles. Furthermore, with antisense oligonucleotides carried by the neoglycoproteins, the concentration required to inhibit cell proliferation is lower than that of the carrier-free antisense oligonucleotides.     

The Intubation Difficulty Scale (IDS): Proposal and Evaluation of a New Score Characterizing the Complexity of Endotracheal Intubation

Background: A quantitative scale of intubation difficulty would be useful for objectively comparing the complexity of endotracheal intubations. The authors have developed a quantitative score that can be used to evaluate intubating conditions and techniques with the aim of determining the relative values predictive factors of intubation difficulty and of the techniques used to decrease such difficulties.

Methods: An Intubation Difficulty Scale (IDS) was developed, based on parameters known to be associated with difficult intubation. It was then evaluated prospectively in a group of 311 consecutive prehospital intubations and 315 intubations in an operating room. In the operating room, the IDS was compared with two other parameters: the time to completion of intubation and the visual analog scale (VAS). Time was measured by an independent observer. Operators in both groups completed a checklist regarding the conditions of intubation.

Results: There is a good correlation between the IDS scale and the VAS assessment of difficulty and time to completion of intubation. VAS and time to completion have a significant but lesser correlation to each other. Comparison of IDS with operator-assessed subjective categorical impression of difficulty by Kruskall-Wallis was statistically significant.     

Autotransfusion-bacterial contamination during hip arthroplasty and efficacy of cefuroxime prophylaxis: A randomized controlled study of 40 patients

40 patients undergoing primary hip arthroplasty, given autologous processed blood transfusion, were randomized to receive no antibiotic prophylaxis (group A, n 20) or cefuroxime (1.5 g single injection; group B, n 20). Bacterial contamination at various steps in the autotransfusion procedure was assessed in liquid and solid culture media. the operation field and the wound drainage blood were never contaminated in either of the groups but some of the suction tips were. Parts of the Vacufix® blood collection bags of group A contained bacteria, but none in group B. Processed red blood cell concentrates in both groups showed bacterial growth. Greater blood loss did not increase the contamination rate in general. Isolated bacteria included the species Staphylococcus epidermidis, coagulase-negative staphylococci and Propionibacteria in both groups, but with different cell counts. in addition, Corynebacterium bovis et minutissimum and Moraxella were identified in group A.

In conclusion, autologous blood transfusion was a safe procedure. If contamination occurred, the bacterial count was low, and the bacteria of low pathogenicity. Antibiotic prophylaxis with cefuroxime reduced this contamination of suction tips and collection bags and limited the transfer of autologous blood products.     

Mandibular fracture not shown by axial computed tomography: Benefit of computed reformation

A 36-year-old man was brought to the emergency department after being assaulted. A mandible series showed a nondisplaced fracture through the angle of the mandible extending through the left third molar tooth. Axial slices from a nonhelical computed tomographic (CT) examination of the head as well as a helical CT examination of the mandible failed to demonstrate the fracture. The fracture was well shown, however, on sagittal CT reformations. Although CT is generally regarded as more sensitive than plain radiography for the detection of fractures, fractures may be overlooked by CT if examination in only one plane is performed.     

A Biomechanical Double Sac (Pericardium-Pebax) for Specially Shaped Artificial Ventricles: A Computerized Study to Evaluate Its Mechanical and Volumetric Properties

Abstract: For original ovoid shaped artificial ventricles. a biomechanical double sac consisting of a biological sac (porcine pericardium) as the blood contact interface and a synthetic sac (Pebax 3533) as the mechanical support to assume systolic-diastolic dynamic constraints was conceived. The volumetric and mechanical properties were assessed with a three-dimensional modeling of Pebax sacs and computerized simulations of their systolic distortions for both right and left ventricular configurations. The stresses and strains of these sacs were represented as quantitative mappings for a maximum end-systolic state and were below the respective threshold values above which the Pebax material is jeopardized for permanent structure impairment. After fatigue tests applied on Pebax strips under the alleged working conditions of Pebax sacs, the material structure was unchanged and maintained its intrinsic mechanical properties. The theoretical maximum stroke volumes were 74.4 cm³ and 62.4 cm for the left and right ventricular configurations, respectively. With these mechanical and volumetric features, the biomechanical double sac concept was considered valid and could be provided for a consequent specific total artificial heart.     

Focused helical appendiceal computed tomography: Technique and interpretation

This article reviews a focused helical appendiceal computed tomographic technique and discusses an approach to appendiceal computed tomographic interpretation.     

Adsorption of Salmon Calcitonin to PLGA Microspheres

Purpose. The interaction of salmon calcitonin (sCT) and poly (d,l-lactide-co-glycolide) was detected during preparation and evaluation of microspheres. The purpose of this study was to quantitate the extent and nature of the interaction. Methods. Blank microspheres were prepared by an aqueous emulsification solvent extraction technique. Adsorption studies were carried out at six concentrations of sCT and three concentrations of microspheres. Adsorption isotherms were constructed using the Langmuir and Freundlich treatments. Results. Adsorption at 1 mg/ml sCT concentration resulted in almost complete depletion of the peptide from the adsorption medium with the time to reach maximum adsorption decreasing with increasing microsphere concentration. At sCT concentrations below 100 µg/ml, a true equilibrium occurred in 1 hour or less while at higher concentrations (up to 350 µg/ml), a transient equilibrium was reached in 1 to 2 hours, followed by further adsorption of the peptide. The adsorption followed the Langmuir isotherm at concentrations below 200 µg/ml, indicating formation of a monolayer. Multilayer interaction, described by the Freundlich isotherm, occurred at higher concentrations and resulted in complete depletion of sCT from the adsorption medium. The affinity constant during monolayer formation was 0.09 and the plateau surface concentration was 5.1 µg/mg. The multilayer peptide-peptide adsorption showed a lower affinity (0.025) but higher capacity (24 µg/mg) than the monolayer peptide-polymer adsorption. Conclusions. The results show that poly (d,l-lactide-co-glycolide) microspheres have a high adsorption capacity for sCT which must be considered in formulating a controlled delivery product of this peptide.