Additive Effects of Sevoflurane and Propofol on γ-Aminobutyric Acid Receptor Function

Background: Previous studies have shown that propofol and sevoflurane enhance the function of [gamma]-aminobutyric acid type A (GABAA) receptors. However, it is not known whether these two drugs modulate the same molecular pathways. In addition, little is known about receptor function in the presence of both propofol and sevoflurane. The aim of this study was to better understand the interactions of propofol and sevoflurane with the GABAA receptor.

Methods: Wild-type [alpha]1, [beta]2, [gamma]2s GABAA receptor subunit complementary DNAs were transfected into human embryonic kidney cells grown on glass coverslips using a calcium phosphate transfection method. After transfection (36-72 h), cells were whole cell patch clamped and exposed to combinations of the following: 0.3-1,000 [mu]m [gamma]-aminobutyric acid (GABA), 0-10 [mu]m propofol, and 0-1,650 [mu]m sevoflurane. Chemicals were delivered to the cells using two 10-channel infusion pumps and a rapid solution exchanger.

Results: Both propofol and sevoflurane alone enhanced the amplitude of GABAA receptor responses to submaximal concentrations of GABA in a dose-dependent manner. The enhancement was underpinned by an increase in the apparent affinity of the receptor for GABA. Coapplication of both anesthetics further enhanced the apparent affinity of the receptor for GABA.     

Prevention of Descending Pneumonia in Rats with Perflubron-delivered Tobramycin

OBJECTIVES: Patients undergoing emergent endotracheal intubation are at increased risk for developing pneumonia. Although numerous strategies have been investigated to reduce ventilator-associated pneumonia (VAP), the incidence of VAP and its associated mortality remains high. This investigation tested the hypothesis that LiquiVent (Alliance Pharmaceutical, San Diego, CA-LV) delivered antibiotics (via spray-dried microspheres-SDM) would improve survival in a rat model of descending gram-negative pneumonia. METHODS: Wistar rats (n = 49) were randomized to receive prophylaxis with 1). nothing (controls); 2). intramuscular (IM) tobramycin, 3). intratracheal LV plus SDM shells (vehicle), 4). intratracheal LV plus SDM shells plus IM tobramycin, or 5). intratracheal LV plus SDM containing 1 mg/kg of tobramycin. All interventions were given 24 hours before a bacterial challenge with 10(8) colony-forming units of intratracheal Klebsiella pneumoniae. Mortality at ten days was the sole outcome measure. Survival in individual groups was compared with controls by Fisher's exact test with Bonferroni correction for multiple comparisons. RESULTS: All animals in the control group died of pneumonia within ten days of bacterial inoculation (0% survival). Prophylaxis with either IM tobramycin or SDM vehicle plus IM tobramycin provided no protection (0% survival). This is in sharp contrast to the cohort receiving pretreatment with tobramycin-containing SDM delivered via LV, in which 60% of the animals survived to study completion (p < 0.05). CONCLUSIONS: Prophylaxis with SDM containing antibiotics delivered in low-dose LV provided significant protection in a rat model of descending gram-negative pneumonia. These data support the hypothesis that perfluorocarbon-delivered intratracheal antimicrobials may be useful in the prevention of VAP.     

Influence of Short‐term Confinement and Exercise on Tibia Development in Growing Pigs

The influence of short‐term confinement and moderate exercise on tibia development was investigated in growing pigs (36–41 kg, 10 weeks at the beginning of the study). Animals were kept for 2 weeks either in individual crates of 0.8 m² (‘confinement’, n = 4) or kept in groups of four animals in large crates of 5.6 m² without (‘control’) or with additional exercise (30 min walking at 5 days/week; ‘exercise’). Bone density and morphological parameters were evaluated by computer tomography (CT). Periosteal apposition and longitudinal growth were determined after polychrome sequential labelling in weekly intervals. Cortical areas of the cross sections at the mid‐shaft and at 75% of the length of the bone measured distal to the carpus by CT were significantly correlated to each other (r = 0.70) and revealed a significant reduction in confined animals. This difference was explained by lower periosteal apposition rates in these animals compared with exercised and group‐housed pigs. Similarly longitudinal growth and the formation and calcification of spongiosa of the tibiae were inhibited by confinement. Thus, 2 weeks of confinement led to significant differences in bone growth and metabolism in young growing piglets when compared with animals with moderate activity.     

Free flap monitoring with continuous tissue oxygen tension measurement

Intraoperative and postoperative free flap monitoring by means of oxygen tension measurement was carried out in 11 patients. We used an invasive flexible microcatheter that allowed for measurement of oxygen tension in all types of free flaps. Two cases of the measured flaps were buried free flaps which do not allow monitoring by clinical assessment. All flaps monitored in this study survived. One case of displacement of the microcatheter occurred. In one patient, the tissue pO₂ monitor successfully detected early vascular thrombosis with subsequent reoperation and salvage of the free flap.     

Synthesis of 1-alkyl-3,4-dihydroisoquinoline derivatives and study of their effect on arterial pressure

A series of 1-alkyl-3,4-dihydroisoquinolines and the related 4-alkyl-1,2-dihydro-benzo[f]isoquinolines was synthesized using reactions of dialkylbenzylcarbinols and their naphthyl analogs with alkylcyanides. Experiments showed that 1-alkyl-6,7-dimethoxy-3,4-dihydroisoquinolines typically produce a hypotensive action, while the benzo-annelated structures usually exhibit a hypertensive effects. The most active compound decreases the arterial pressure in cats by 52 Torr and the effect lasts for about 4 hours. __________ Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 40, No. 3, pp. 15–17, March, 2006.     

Falls and consequent injuries in hospitalized patients: effects of an interdisciplinary falls prevention program

Background  

Patient falls in hospitals are common and may lead to negative outcomes such as injuries, prolonged hospitalization and legal liability. Consequently, various hospital falls prevention programs have been implemented in the last decades. However, most of the programs had no sustained effects on falls reduction over extended periods of time.