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.     

Primary glioblastomas and anaplastic astrocytoma in a glioma family.

A 72-year-old man presented with a short duration of symptoms relating to a right fronto-parietal glioblastoma and a family history of children with brain tumours. Analysis of the patient's family tree revealed that out of seven children, he had a living son with anaplastic astrocytoma, a daughter who had died with a glioblastoma, and a son who had died with a histologically undiagnosed intrinsic brain tumour. One niece was also thought to have died from a brain tumour. All of the other affected family members had onset in their third or fourth decades. Tissue was only available from two of the affected individuals, precluding familial genetic analysis at this stage. There is no clinical evidence to support a diagnosis of a multiple cancer or neurocutaneous syndrome in this family. In view of what is known about the genetics of familial glioma, it is interesting to note the clinical evidence of both 'primary' glioblastoma and anaplastic astrocytoma in the same kindred.     

Increasing the efficiency of Monte Carlo cohort simulations with variance reduction techniques.

The authors discuss techniques for Monte Carlo (MC) cohort simulations that reduce the number of simulation replications required to achieve a given degree of precision for various output measures. Known as variance reduction techniques, they are often used in industrial engineering and operations research models, but they are seldom used in medical models. However, most MC cohort simulations are well suited to the implementation of these techniques. The authors discuss the cost of implementation versus the benefit of reduced replications.     

Cortical plasticity: effect of high and low intensity conditioning electrical stimulations (100 Hz) on SEPs to painful finger stimulation.

OBJECTIVE: To study the effect of high-frequency (100 Hz) repetitive conditioning electrical stimulation (CES, 10 min) on human somatosensory evoked potentials (SEPs) to evaluate if short-term cortical plasticity could be induced. METHODS: Painful electrical stimulations were applied to thumb (D1) and little finger (D5) fingertips, respectively. The 124-channel EEG was recorded from 10 healthy male volunteers. Peak stages around 34, 45, 212, 331 ms were analyzed with focal maximum amplitude (FA) and area magnitude (AM) of scalp field potential, topography, and equivalent current dipole source localisation, comparing before and after two-level CES (high- vs. low-level) applied to the He-Gu acupoint. RESULTS: After a high-level CES, the positive FA and AM of the current efflux showed a significant increase at the early phase 34 ms, and significantly decreased at 45 ms in D1 SEPs. The negative FA and AM of the current influx were significantly increased at late phase 350 ms of the D5 SEPs. Only 36 ms, the z-axis position of dipole was significantly changed from (x: -15.9 mm, y: 29.6 mm, z: 43.9 mm) to (x: -12.9 mm, y: 29.4mm, z: 51.5mm) for the D5 SEPs. CONCLUSIONS: The high-level CES significantly attenuated the subsequent cortical activation (45 ms peak for D1 stimulation). Both low- and high-level CES significantly enhanced the late activities (226, 350 ms) in D5 stimulation. This may be explained by pain sensation change at the level of subcortical cingulate cortex induced by the site-dependent post-effect of CES. SIGNIFICANCE: This study showed cortical plasticity induced by conditioning somatosensory stimulation.     

Pharmacological therapy of vascular malformations of the gastrointestinal tract.

Vascular malformation (AVM) in the gastrointestinal tract is an uncommon, but not rare, cause of bleeding and iron deficiency anemia, especially in an aging population. While endoscopic coagulative therapy is the method of choice for controlling bleeding, a substantial number of cases require additional therapy. Adjunctive or even primary phamacotherapy may be indicated in recurrent bleeding. However, there is little evidence-based proof of efficacy for any agent. The bulk of support is derived from anecdotal reports or case series. The present review compares the outcome of AVM after no intervention, coagulative therapy or focus on pharmacological agents. Most of the literature encompasses two common AVMs, angiodysplasia and hereditary hemorrhagic telangiectasia. Similarly, the bulk of information evaluates two therapies, hormones (estrogen and progesterone) and the somatostatin analogue octreotide. Of these, the former is the only therapy evaluated in randomized trials, and the results are conflicting without clear guidelines. The latter therapy has been reported only as case reports and case series without prospective trials. In addition, other anecdotally used medications are discussed.     

Effect of a patellar realignment brace on patellofemoral relationships: Evaluation with kinematic MR imaging

The effect of a newly developed patellar realignment brace was evaluated in 21 patellofemoral joints (19 patients) with patellar subluxation (13 joints with lateral subluxation and eight with medial subluxation) by using active-movement, loaded kinematic magnetic resonance (MR) imaging. Sixteen patellofemoral joints (76%) demonstrated a qualitative correction of or improvement in patellar subluxation (ie, centralization of the patella or a decrease in the displacement of the patella) after application of the brace. Four of the five “failures” occurred in patellofemoral joints that had patella alta and/or dysplastic bone anatomy. These results indicate that the patellar realignment brace was able to counteract patellar subluxation in the majority of patellofemoral joints studied, as shown by active-movement, loaded kinematic MR imaging. This brace appears to be useful for conservative treatment of patients with patellofemoral joint pain secondary to patellar malalignment and maltracking.     

How to assess fetal metabolic acidosis from cord samples.

The degree of metabolic acidosis at birth has been calculated in cord artery and vein samples from 21 term fetuses with cord artery pH less than 7.20. The aim of the study was to compare base deficit values calculated from either Siggaard-Andersen alignment nomogram (BD blood) or the Acid-Base chart (BD extra cellular fluid, BDecf). BDblood was found to be consistently higher in the cord artery as compared with BDecf, 13.2 +/- 3.5 and 9.9 +/- 2.9 mmol/l (Mean +/- SD), respectively. A significant correlation was found between cord artery PCO2 and BDblood whereas BDecf appeared unaffected by PCO2. In cases with cord entanglement BDecf a-v differences were increased to 3.4 +/- 2.3 mmol/l as compared with the small a-v difference noted in acidotic cases without cord entanglement, 1.1 +/- 1.25 mmol/l. It is speculated that with acutely emerging, intermittent asphyxia due to cord compression, a cord artery and vein difference in metabolic acidosis may exist and where the vein captures the basal level and the artery the acute changes. It is concluded that BDecf in both cord artery and vein add valuable information on the mechanisms behind metabolic acidosis.     

Older donors and kidney transplantation

Reluctance to use kidneys from older donors (>50 years of age) is based on reports of inferior results. We reviewed our experience with 45 kidneys transplanted from older donors. Primary nonfunction, immediate graft function, and 1-, 2- and 3-year graft survival rates were similar to those obtained with kidneys transplanted from donors aged between 20 and 40 years. Renal function at 1 year (as measured by serum creatinine) was poorer in kidneys from older donors. No beneficial effect with respect to graft survival was noted with cyclosporin therapy compared to conventional immunosuppression; however, the numbers are small. We conclude that kidneys from older donors are a valuable source for transplantation.