Changes in cerebrovascular reactivity in healthy adults after acute exposure to high altitude.

OBJECTIVE: To study changes in the cerebrovascular reactivity (CVR) at different altitude area in healthy adults. SUBJECTS AND METHODS: CVR was tested using transcranial Doppler combined with CO2 inhalation, near-infrared spectroscopy (NIRS) was used to detect the regional cerebral oxygen saturation (rScO2). Blood samples were collected, and the vasoactive substances in serum were detected using the enzyme-linked immunosorbent assay. In this study, 59 healthy adults were divided into 3 groups: low altitude group, medium altitude group and high altitude group. All the indicators in low altitude group were tested at 24h before departure and after arrival from Beijing (at an altitude of 44.4 m) to Xining (at a medium altitude of 2200 m). Then, after resting for 48h, all the indicators were tested at 24h and 48h after arrival from Xining (at a medium altitude of 2200 m) to Yushu Jiegu town (at a high altitude of 3700 m) together with those at the medium altitude. Intergroup comparisons were made for the subjects in the three altitudes. RESULTS: There was an increase in the CVR in low altitude group after acute exposure to high altitude, and the difference was significant (CVR: 1.94re was vs. 0.91±0.53, p<0.001); the CVR index was increased, and the difference was significant [cerebrovascular reserve index (CVRI): 3.65he CVR vs. 1.37e CVR, p<0.001]; the rScO2 level was decreased with the increase of altitude, and the difference was significant [(66.78±4.61)% vs. (70.29±4.52)%, p<0.001]. The levels of vasoactive substances in low altitude group were decreased after acute exposure to high altitude compared with those before exposure: NO: [(79.14±9.54) µmol/L vs. (58.01±9.93) µmol/L, p<0.001]; serum eNOS level was increased, and the difference was significant [(77.23±6.20) pg/ml vs. (65.07±9.82) pg/ml, p<0.001]; EPO: [(84.68±13.16) pg/ml vs. (65.01±5.92) pg/ml, p<0.001]; VEGF: [(71.91±11.62) pg/ml vs. (54.92±11.86) pg/ml, p<0.001]; sFlt: [(384.18±42.73) pg/ml vs. (320.62±78.96) pg/ml, p<0.001]. There was also an increase in CVR in medium altitude group after acute exposure to high altitude, and the difference was significant [CVR: 2.00±0.79 vs. 0.91±0.66, p<0.001]; the difference of CVRI was significant [3.83±0.67 vs. 1.67±0.87, p<0.001]; rScO2 was slightly decreased with the increase of altitude, and the difference was not statistically significant [(67.53±4.61) % vs. (69.63±5.59) %, p<0.001]. Before exposure to high altitude area, the levels of NO, NOS, EPO, VEGF, and sFlt in low and medium altitude groups were higher than those in high altitude group. CVR level of subjects at different altitudes was negatively related to the ScO2 (r=-0.91) but positively related to NO and NOS levels (rs=0.89, r=0.75); CVR was moderately related to VEGF and EPO (rs=0.45, r=0.42). rScO2 was positively related to RBC, HB and VEGF levels (r=0.89, r=0.75, rs=0.86), but had a moderately negative correlation with NO and NOS levels (rs=-0.52, r=-0.57). CONCLUSIONS: After subjects at a low altitude are exposed to high altitude rapidly, CVR is increased, RBC and vasoactive substances in serum, such as NO, eNOS, and EPO, are dramatically increased, VEGF is increased first and then decreased, sFlt-1 level is increased gradually, and rScO2 level is gradually decreased with the increase of altitude, indicating the local brain anoxia of subjects at a high altitude.

Efficacy of Directigen RSV testing in patient management following admission from a paediatric emergency department.

We investigated the use of the Directigen Respiratory Syncytial Virus test performed under 'Stat Laboratory' conditions, in the management of infants after admission from the Paediatric Emergency Department (ED). The study group consisted of 242 consecutive paediatric ED patients tested by Directigen in the Stat laboratory during the winter 1995-1996 respiratory virus season. Specimens were submitted to the Virology Laboratory for confirmatory consensus testing utilizing in part, an in-house multiplex immunofluorescence assay (IFA) and conventional virus isolation methodologies. The sensitivity, specificity, positive and negative predictive values for Directigen, IFA, and isolation, were 71, 91, 85, 80%; 98, 100, 100, 99%; and 51, 100, 100, 72% respectively. Re-testing of 17 discordant original NP aspirates using Directigen, suggested that errors were due to technologist interpretation as well as to overt assay failure. The low analytical sensitivity and specificity of Directigen precludes its use in the clinical setting described in this study. Evening or weekend specimen collection, followed by IFA testing in a centralized Virology Laboratory at the start of the next working day, produces reliable test results. Among the small number of pediatric patients who might be candidates for antiviral therapy IFA testing should be made available on an on-call basis by Virology Laboratory.

Antagonism of paraoxon intoxication by recombinant phosphotriesterase encapsulated within sterically stabilized liposomes.

This investigation effort is focused on increasing organophosphate (OP) degradation by phosphotriesterase to antagonize OP intoxication. For these studies, sterically stabilized liposomes encapsulating recombinant phosphotriesterase were employed. This enzyme was obtained from Flavobacterium sp. and was expressed in Escherichia coli. It has a broad substrate specificity, which includes parathion, paraoxon, soman, sarin, diisopropylfluorophosphate, and other organophosphorous compounds. Paraoxon is rapidly hydrolyzed by phosphotriesterase to the less toxic 4-nitrophenol and diethylphosphate. This enzyme was isolated and purified over 1600-fold and subsequently encapsulated within sterically stabilized liposomes (SL). The properties of this encapsulated phosphotriesterase were investigated. When these liposomes containing phosphotriesterase were incubated with paraoxon, it readily degraded the paraoxon. Hydrolysis of paraoxon did not occur when these sterically stabilized liposomes contained no phosphotriesterase. These sterically stabilized liposomes (SL) containing phosphotriesterases (SL)* were employed as a carrier model to antagonize the toxic effects of paraoxon by hydrolyzing it to the less toxic 4-nitrophenol and diethylphosphate. This enzyme-SL complex (SL)* was administered intravenously to mice either alone or in combination with pralidoxime (2-PAM) and/or atropine intraperitoneally. These results indicate that this carrier model system provides a striking enhanced protective effects against the lethal effects of paraoxon. Moreover when these carrier liposomes were administered with 2-PAM and/or atropine, a dramatic enhanced protection was observed.