Increased physiological dead space/tidal volume ratio during exercise in burned children

During a transjugular intrahepatic portosystemic shunt (TIPS) procedure, a Strecker stent was accidently pushed into the superior mesenteric vein. After successful shunt placement, the stent was withdrawn into the hepatic vein. A multipurpose basket catheter was attached to the distal end of the stent and a loop snare to the proximal end. In this way it was possible to stretch the stent and retrieve it percutaneously through the jugular sheath.     

Evidence of a critical period of airway instability during central apneas in preterm infants

The timing and magnitude of airway narrowing in central apneas is unknown. We have developed a method of apnea classification that relies on the transmission of cardiac airflow oscillation to indicate airway patency. Using a theoretical model, we showed that the amplitude of the cardiac airflow oscillation is proportional to airway diameter for small lumens. While in the majority of central apneas the amplitude of the cardiac airflow oscillation remains nearly constant, in a subset of events the waveform decreases with time, suggesting airway narrowing. We hypothesized that this is not a random occurrence but reflects a critical period of airway instability during central apnea. To test this hypothesis we studied 41 preterm infants. Of 4,456 central apneas, 585 had a decrease in the amplitude of the cardiac oscillation. The amplitude of the cardiac airflow oscillation during an apnea was recorded to provide a dynamic measure of changes in airway diameter with time. To allow for comparisons between patients the amplitude of each cardiac airflow oscillation was expressed as a proportion of the maximum amplitude observed in each infant. We then compared the amplitude at multiple successive 0.5 s intervals with the amplitude of the cardiac airflow oscillation observed at the apnea outset using ANOVA. We found a significant decrease in cardiac airflow oscillation after only 1 s irrespective of the apnea duration (3 to 16 s). We conclude that airway narrowing during central apnea is not a random occurrence but appears shortly after the onset of the apnea. We speculate that the phenomenon is secondary to passive airway relaxation.     

Pharmacokinetics of a single dose of teicoplanin in burn patients

Patients with severe burns are susceptible to infection with Gram-positive organisms including methicillin-resistant Staphylococcus aureus, and often require higher antibiotic dosages compared with other patients. This study examined the pharmacokinetics of a single iv dose of teicoplanin (12 mg/kg) in 15 adults and five children with severe burns. Adults were aged 21-82 years with a median total body surface area (TBSA) burn of 30% (range 15-60%). Children were aged 10 months-l0 years with median TBSA burn of 15% (10-30%). At 12 h, the median serum teicoplanin concentration was 12.8 mg/L (9.027.1 mg/L) in adults and 7.6 mg/L (6.6-l0.8 mg/L) in children, (P < 0.01); at 24 h, the corresponding values were 8.3 mg/L (4.6-l2.9 mg/L) and 5.2 mg/L (4.2-6.0 mg/L). Using a three-compartment model, the median terminal half life in adults was 114 h (47-278 h). Children fitted a two-compartment model with a terminal half-life of 38 h (2l-41 h). The median concentration of teicoplanin in fluid from the burn wound was 60% of the serum antibiotic concentration. A single iv dose of 12 mg/kg of teicoplanin was sufficient to produce therapeutic serum concentrations in burn patients for 24 h, but monitoring of antibiotic levels in serum may be advisable in those with high total clearance, especially children.     

Species differences in the physical and transport properties of airway secretions

Four cases of severe Lepiota poisoning, including three which developed toxic fulminant hepatitis treated by orthotopic hepatic transplantation, are reported here. The toxicity of the Lepiota is discussed as well as the indications for hepatic transplantation in poisonings due to amatoxin-containing mushrooms.     

Vitamin E as a universal antioxidant and stabilizer of biological membranes

The known literature data concerning the mechanisms of molecular action of vitamin E in biological membrane systems are reviewed. The role of vitamin E, possessing a broad range of biological activities, as a universal stabilizer of biological membranes in normal oxygen metabolism and peroxidation, and also in disorders of normal metabolism resulting in pathological alterations, has been discussed. The participation of vitamin E in redox reactions taking place in lipid media, its interaction with singlet oxygen, free fatty acids and enzyme systems are considered. Physiological effects of vitamin E and its ability to prevent numerous pathologies are also considered. Vitamin E was concluded to be a universal participant of antioxidant defence reactions in biological membranes, since it acts at all stages of membrane oxidative damage.     

Age-associated alterations in calcium current and its modulation in cardiac myocytes

Stimulatory effects of several types of adjuvants on secondary antibody response to inactivated Newcastle disease virus (iNDV) were examined in chickens. For this purpose, animals were primed with iNDV without adjuvant resulting in a low but significant antibody response, boosted with iNDV plus adjuvant 3 weeks later, and analysed for specific antibody titres in serum 3 weeks after the booster. Water-in-mineral oil emulsion (W/O) caused significant increase in antibody titres measured in an indirect enzyme-linked immunosorbent (ELISA), haemagglutination inhibition (HI), and virus neutralisation (VN) assay. The adjuvants tested included three oil-in-water emulsions (i.e. mineral oil-in-water, sulpholipo(SL)-Ficoll400/squalane-in-water and sulpholipo-cyclodextrin/squalane-in-water), three negatively-charged polymers with high molecular weight (i.e. polyacrylate, polystyrenesulphonate and sulpho(S)-Ficoll400) and two surface-active agents (i.e. dimethyldioctadecylammonium bromide (DDA) and Quil A). These adjuvants enhanced significantly the secondary immune response but none reached the titre obtained with W/O. Combinations of adjuvants with distinct physicochemical properties, i.e. polyacrylate and DDA revealed only slight, beneficial effects. We concluded that the various types of adjuvants tested can stimulate secondary immune responses in primed animals but that W/O is superior.     

Characterization of the MN gp120 HIV-1 vaccine: antigen binding to alum

PURPOSE: The characterization of recombinant MN gp120/alum vaccine requires the study of the gp120-alum interaction for the successful formulation of an alum-based HIV-1 vaccine. METHODS: Several observations suggest that the gp120-alum interaction is weak, wherein buffer counterions such as phosphate, sulfate, bicarbonate may cause the desorption of gp120 from alum. Comparison of gp120 with other proteins using particle mobility measurements shows that the weak binding of gp120 to alum is not an anomaly. Serum and plasma also cause desorption of gp120 from alum with a half-life of only a few minutes, wherein this half-life may be faster than the in-vivo recruitment of antigen presenting cells to the site of immunization. RESULTS: Immunization of guinea pigs, rabbits and baboons with gp120 formulated in alum or saline demonstrated that alum provides adjuvant activity for gp120, particularly after early immunizations, but the adjuvant effect is attenuated after several boosts. CONCLUSIONS: These observations indicate that both the antigen and the adjuvant require optimization together.     

Binding of the peroxisomal targeting sequence SKL is specified by a low-affinity site in castor bean glyoxysomal membranes. A domain next to the SKL binds to a high-affinity site

The carboxyl-terminal amino acid sequence serine-lysine-leucine (SKL) is the consensus peroxisomal targeting sequence 1 (PTS1) and is sufficient to direct a polypeptide to peroxisomes in vivo in plants, animals, and yeasts. However, there are also two sites on alkali-stripped glyoxysomal membranes from castor bean (Ricinus communis) endosperm that bind the peptide YHKHLKPLQSKL (SKLp), the sequence of the last 12 amino acids of acyl-coenzyme A oxidase (N.E. Wollins, R.P. Donaldson [1994] J Biol Chem 289: 1149-1153). It was hypothesized that one of these sites interacts with information other than the PTS1. To explore the sequence requirements for each SKLp binding site, we tested the peptides YHKHLKPQSKG and YHKHLKPLQS and found that they bound to the high-affinity site, but not to the low-affinity site. When the high-affinity site was blocked with YHKHLKPQSKG, SKLp bound to the low-affinity site with a dissociation constant (Kd) of 8.5 microM. In an attempt to disrupt high-affinity binding, two the upstream, positively charged residues were replaced with negatively charged residues to make the peptide YHKETEPLQSKL. YHKETEPLQSKL did not bind to either site on the glyoxysomal membranes. These results indicate that the PTS1 binds to the low-affinity site and that the adjacent, positively charged domain binds to the high-affinity site.