Anaesthesia for neurosurgery in the sitting position.

The sitting position offers many advantages in terms of surgical access for posterior fossa and posterior cervical spine surgery. However, these advantages must be balanced against the risks which include venous and paradoxical arterial air embolism, cerebral and myocardial ischaemia secondary to hypotension, and complications of the positioning itself. These are largely in the domain of the neuroanaesthetist. In this paper, therefore, we will review the advantages, disadvantages and management of complications of the sitting position, from the neuroanaesthetist's perspective.     

The versatile rhomboid (Limberg) flap

The rhomboid (Limberg) flap can be used to close defects almost anywhere on the body. It is versatile in that a random pattern flap can be raised from any one or all corners of the rhomboid. The defect is filled with tissue of the same thickness and colour, and with good vascularity. The present paper demonstrates the versatility of the rhomboid flap.     

Disposition of tacrolimus in isolated perfused rat liver: influence of troleandomycin, cyclosporine, and gg918.

The disposition of tacrolimus and the influence of cyclosporine, troleandomycin, and GF120918 (GG918, or N-[4-[2-(1,2,3,4-tetrahydro-6,7-dimethoxy-2-isoquinolinyl)-ethyl]-phenyl]-9,10-dihydro-5-methoxy-9-oxo-4-acridine carboxamine) on its hepatic disposition were examined in the isolated perfused rat liver. Livers from groups of rats were perfused in a recirculatory manner following a bolus dose of tacrolimus (100 microg), a substrate for P-glycoprotein (P-gp) and CYP3A, or with felodipine (200 microg), a substrate only for CYP3A. Perfusions of each substrate were also examined in groups of rats in the presence of the inhibitors: troleandomycin (20 microM, CYP3A inhibitor), GG918 (1 microM, P-gp inhibitor), or cyclosporine (10 microM, CYP3A and P-gp inhibitor). In all experiments, perfusate and bile were collected for 60 min. Tacrolimus, felodipine, and their primary metabolites were determined in perfusate and bile by liquid chromatography/tandem mass spectrometry. The area under the curve (AUC) from 0 to 30 min was determined. For the dual CYP3A and P-gp substrate, tacrolimus, AUC +/- S.D. was decreased from control (2,260 +/- 430 ng. min/ml) by GG918 (1,730 +/- 270 ng. min/ml, P < 0.05) and was increased by troleandomycin (5,200 +/- 2,470 ng. min/ml, P < 0.05) and cyclosporine (4,390 +/- 2,080 ng. min/ml, P < 0.05). For the exclusive CYP3A substrate, felodipine, AUC was unchanged from control by GG918 but increased by troleandomycin and cyclosporine. It is concluded that GG918 increased the hepatic exposure of tacrolimus by inhibiting the canalicular P-gp transport, whereas GG918 has no effect on hepatic disposition of felodipine. These results support our hypothesis that the hepatic metabolic clearance of a dual substrate will be increased by inhibiting the efflux transporter.     

Detection of chromosomal alterations affecting the 1cen-1q12 region in irradiated granulocytes and lymphocytes by multicolour FISH with tandem DNA probes

A multicolour tandem labelling fluorescence in situ hybridization(FISH) procedure was used to compare the frequencies of radiation-inducedchromosome breakage and hyperdiploidy of chromosome 1 occurringin non-cultured granulocytes and Go lymphocytes with those observedin cultured metaphase and interphase lymphocytes. Whole blood,obtained from healthy male donors, was exposed in vitro to 0,100, 200, 300 and 400 cGy of ionizing radiation from a ¹³⁷Cssource. Aliquots containing granulocytes and Go lymphocytesfrom each dose were treated immediately with hypotonic KCl onice and harvested. Cells were hybridized with     

Alcohol inhibition of NMDA-stimulated catecholamine efflux in aging brain.

The influence of aging on the ability of ethanol to inhibit N-methyl-D-aspartate-stimulated catecholamine overflow in rat brain was examined. Alcohol effects on N-methyl-D-aspartate stimulated [3H]norepinephrine or [3H]dopamine overflow from the cortex, hippocampus, and striatum of aged (24-28 months) middle aged (12-14 months), and young (3-5 months) rats were examined. N-methyl-D-aspartate (500 microM) stimulated catecholamine overflow in all brain regions, with aged rats showing declines in overflow of 33% in the hippocampus and 41% in the striatum. Alcohol (30-200 mM) produced a concentration-dependent inhibition of overflow at all ages and brain regions tested. The IC50 for alcohol inhibition of NMDA-stimulated catecholamine release was not significantly different in aged brain or across brain regions. These results indicate that alcohol's ability to inhibit NMDA-stimulated catecholamine release is not significantly altered with aging.     

Efficacy and safety of ezetimibe coadministered with pravastatin in patients with primary hypercholesterolemia: a prospective, randomized, double-blind trial.

AIMS: To evaluate the efficacy and safety of ezetimibe 10 mg administered with pravastatin in patients with primary hypercholesterolemia. METHODS AND RESULTS: After dietary stabilization, 2-12 week screening/washout period, and 4-week, single-blind, placebo lead-in period, 538 patients with baseline LDL-C > or =3.8 to < or =6.5 mmol/l and TG < or =4.0 mmol/l were randomized to one of eight possible treatments administered daily for 12 weeks: ezetimibe 10mg; pravastatin 10, 20, or 40 mg; ezetimibe 10 mg plus pravastatin 10, 20, or 40 mg; or placebo. The primary efficacy endpoint was percent reduction in LDL-C from baseline to study endpoint for ezetimibe 10 mg plus pravastatin (pooled doses) compared to pravastatin alone (pooled doses) and ezetimibe alone. The combined use of ezetimibe and pravastatin resulted in significant incremental reductions in LDL-C and TG compared to pooled pravastatin alone (p<0.01). Coadministration therapy reduced LDL-C by 34-41%, TG by 21-23%, and increased HDL-C by 7.8-8.4%, depending on the dose of pravastatin. The combined regimen was well tolerated, with a safety profile similar to pravastatin alone and placebo. CONCLUSIONS: When coadministered with pravastatin, ezetimibe provided significant incremental reductions in LDL-C and TG and was well tolerated with a safety profile similar to pravastatin alone.     

The effects of X monosomy on brain development: Monozygotic twins discorcant for Turner's syndrome

Monosomy for the X chromosome is the most frequent cause of Turner's syndrome, a common clinical syndrome associated with particular physical and neurobehavioral features. The results from comprehensive assessment of prepubertal monozygotic female twins discordant for X monosomy are presented. Zygosity was established with DNA Fingerprinting and no evidence of chromosomal mosaicism was seen in either child. Physical features in the affected twin were relatively mild with respect to the full spectrum of physical malformations and disabilities associated with Turner's syndrome. The neurobehavioral phenotypes of the twins were compared. Although both sisters scored in the superior range of intelligence, the affected twin's Performance IQ was 18 points less than her sister, whereas Verbal IQ showed only a 3-point difference between the sisters. Other relative differences were noted within the executive, visuospatial, and visuomotor domains of function. Behavioral evaluation indicated greater problems with attention, hyperactivity, and anxiety in the affected twin. Quantitative analysis of brain anatomy revealed evidence of both general and regional effects of X monosomy on neurodevelopment. Cerebrospinal fluid volume was increased by 25% in the affected twin compared with her sister with a corresponding decrease in gray matter volume. The right frontal, right parietal–occipital, and left parietal-perisylvian regions showed the greatest discrepancy between the sisters with respect to increased cerebrospinal fluid and decreased gray matter volumes in the twin with X monosomy. Differences in the posterior fossa were also noted with a 50% relative increase in the volumes of the fourth ventricle and cisterna magna and a 10 to 15% relative reduction in size of the cerebellar vermis, pons, and medulla in the affected twin. The association between the neurobehavioral and neuroanatomical findings in the affected twin is discussed. The unique nature of the naturally occurring genetic phenomenon seen in this twin pair provides an opportunity to more fully elucidate the neurobehavioral phenotype associated with X monosomy and Turner's syndrome.     

Ischemia-reperfusion-induced muscle damage: Protective effect of corticosteroids and antioxidants in rabbits

We examined the potential protective effect of pretreatment with corticosteroids or antioxidants (ascorbic acid or allopurinol) in rabbits with reper-fusion-induced damage to skeletal muscle after ischemia.

4 hours of limb ischemia induced by a pneumatic tourniquet, followed by reperfusion for 1 hour, caused a considerable amount of ultrastructural damage to the anterior tibialis muscles accompanied by a rise in circulating creatine kinase activity. Pretreatment of animals with depomedrone by a single 8 mg bolus injection led to a preservation of the anterior tibialis structure on both light and electron microscopy. High-dose continuous intravenous infusion with ascorbic acid (80 mg/hr) throughout the period of ischemia and reperfusion also preserved skeletal muscle structure, although allopurinol in various doses had no protective effect.

These data are fully compatible with a mechanism of ischemia/reperfusion-induced injury to skeletal muscle, involving generation of oxygen radicals and neutrophil sequestration and activation. They also indicate that damage to human skeletal muscle caused by prolonged use of a tourniquet is likely to be reduced by simple pharmacological interventions.