Results of early surgical evacuation of packed intraventricular hemorrhage from aneurysm rupture in patients with poor-grade subarachnoid hemorrhage.

OBJECT: The goal of this study was to evaluate the results of early surgical evacuation of "packed" intraventricular hemorrhage (IVH) in patients with poor-grade subarachnoid hemorrhage (SAH). METHODS: The authors performed surgery within 24 hours after onset of SAH, identified on neuroimaging as a cast distending the ventricular system, in 74 patients with poor-grade SAH (World Federation of Neurosurgical Societies Grades IV and V) without intracerebral hemorrhage. Eighteen of these patients had packed IVH; in these patients the intraventricular clots were extensively evacuated via frontal corticotomy performed under microscopic view. CONCLUSIONS: Overall, 42% of the 74 patients undergoing craniotomy in the acute stage had favorable outcomes, whereas 30% died. Using multivariate analysis, variables significantly associated with favorable outcome in patients with poor-grade SAH included absence of a packed intraventricular clot on computerized tomography scanning; absence of a history of cardiac disease; and a Glasgow Coma Scale score of 11 or 12. None of the 18 patients who had packed IVH had favorable outcomes and seven of these died. In six recently treated patients with packed IVH, which was examined using fluid-attenuated inversion recovery imaging, extensive periventricular brain damage was found both immediately after surgery and during the chronic stage. Accordingly, the authors believe that irreversible periventricular brain damage is already complete immediately after packed IVH occurs.     

Lower plasma levels of haloperidol in smoking than in nonsmoking schizophrenic patients.

The impact of smoking on plasma haloperidol (HAL) concentrations was investigated in 66 Japanese male schizophrenic inpatients treated orally with HAL. The subjects consisted of 22 nonsmokers and 44 smokers each smoking ten cigarettes per day. Plasma concentrations of HAL were determined by an enzyme immunoassay method. There were significant positive correlations between the plasma HAL concentration and the daily dose of HAL per kg body weight (Y = 58.1X-0.01 (r = 0.86)). Smokers had significantly lower HAL concentrations per daily dose of HAL/kg body weight than nonsmokers (smokers vs. nonsmokers = 54.3+/-16.6 vs. 70.6+/-23.2 ng/mL/mg/kg). In doses less than 0.2 mg/kg of HAL, smokers showed significantly lower HAL concentrations per daily dose of HAL/kg body weight than nonsmokers (smokers vs. nonsmokers = 55.1+/-14.4 vs. 79.5+/-27.1 ng/mL/mg/kg), whereas no significant difference in HAL concentrations per daily dose of HAL/kg body weight was observed between smokers and nonsmokers when treated with more than 0.2 mg/kg (smokers vs. nonsmokers = 52.9+/-20.7 vs. 60.0+/-11.1 ng/mL/mg/kg). Our results indicate that smoking may induce the enzyme(s) metabolizing HAL, which results in lower plasma HAL concentrations in smokers than in nonsmokers, particularly at low doses of HAL.     

Competitive adsorption of magnesium and calcium ions onto synthetic and biological apatites

Summary Magnesium (Mg) is a conspicuous constituent of hard tissues but its possible role in biomineralization is poorly understood. It is possible that Mg²⁺ adsorbed onto bioapatites may contribute to the modulation of crystal growth as such inhibitory activity has been reported for synthetic apatites. The present study was undertaken to determine the adsorption isotherms of Mg ions onto synthetic apatites and biominerals in tooth and bone tissues in the presence of other ions of natural occurrence. Synthetic crystals used as adsorbents were hydroxyapatite and, as a better prototype for the biomineral, Mg-containing carbonatoapatite. Human enamel and dentin materials were obtained from extracted, caries-free, permanent teeth. Porcine dentin materials at two developmental stages were obtained from erupted deciduous and unerupted permanent teeth of a 6-month-old slaughtered piglet. Porcine bone was obtained from the cortical portion of the mandible of the same animal. All biomineral samples were pulverized and then treated by plasma ashing (deproteination) at about 60°C. Each of the powdered samples was equilibrated in solutions containing various initial concentrations of Mg²⁺, Ca²⁺, and Na⁺ (or K⁺) as nitrate salts. Following equilibration, concentrations (and activities) of magnesium and calcium ions in the experimental solution were determined. The pH values of the equilibrium solutions were in the range of 6.2–6.5. Experimental data of the Mg adsorption onto hydroxyapatite were interpreted on the basis of a Langmuir-type model for binary systems assuming competition of Mg²⁺ and Ca²⁺ for the same adsorption sites on the crystal surfaces of the apatites. According to this model, the adsorbed Mg is expressed as a function of the ionic activity ratio (Mg²⁺)/(Ca²⁺) in the equilibrium solution. The model contains two parameters, the adsorption selectivity constant K_s and the maximum number of adsorption sites N (mol/g). The numerical values of K_s were similar for all adsorbents used (synthetic and biological) and indicated the preferential adsorption of Ca²⁺ probably due to spacial restrictions extending to the very surface of the crystals. The initial level of Mg²⁺ in the surface pool was different in the various biominerals, probably reflecting the composition of fluid in which the biominerals were formed. Whereas the surface pool of Mg of human enamel was marginal, only 5% of the total Mg, significant fractions of the total Mg in human and porcine dentins (about 20–30%), and porcine bone (about 40%) existed on the crystal surfaces. There were significant differences in the total Mg and the value of the parameter N between young (unerupted) and mature (erupted) dentin minerals. It was ascertained that the occupancy of adsorption sites by Mg ions became greater with maturation of the dentin tissues. The overall results suggest that the Mg-mineral interaction in tooth and bone tissues may be a highly tissue-specific process, presumably reflecting differences in fluid composition (particularly Ca and Mg activities) responsible for biomineralization.     

The effects of urinastatin on the plasma levels of granulocyte elastase during open heart surgery under simple deep hypothermia

Changes in granulocyte elastase (GLE) and -gluculonidase (-gl) were observed during open heart surgeries which were performed under deep hypothermia with surface cooling. In addition, the effect of urinary trypsin inhibitor, urinastatin, on the activities of these enzymes was studied. The patients were divided into three groups, namely group U-I with intravenous injection of 6000u·kg^–1 of urinastatin before cooling, group U-II administered with an additional 6000u·kg^–1 after warming to 30°C, and an untreated group (Group C). The plasma level of GLE increased significantly in the three groups compared with the level before cooling respectively. In the group U-II, the GLE level after the warming was lower than that in the control group. The serum level of -gl increased significantly in the three groups at the end of rewarming (36°C). The release of GLE from lysosomes in granulocytes was inhibited in the group U-II. The insufficient inhibition of GLE release in the group U-I is probably due to relatively short half-life of urinastatin. Therefore double administration of 6000u·kg^–1, before and after the cooling, may be required to achieve the therapeutic effect. Consequently, urinastatin appears to be useful in open heart surgery under deep hypothermia with surface cooling.(Kawamura T, Shimoda Y, Wakusawa R: The effects of urinastatin on the plasma levels of granulocyte elastase during open heart surgery under simple deep hypothermia. J Anesth 6: 269–276, 1992)     

Anesthetic management of a patient with Hallermann-Streiff syndrome

Key words  airway management - difficult intubation - Hallermann-Streiff syndrome     

Renal tubular dysfunction in children living in the Aral Sea Region.

BACKGROUND: The Aral Sea region is a natural area seriously polluted by human activities. Recent surveillance revealed the increased prevalence of diverse chronic diseases in children. AIMS: To investigate the function of renal tubules, which are most at risk of damage as a result of heavy metal intoxication, in children of the Aral Sea region. METHODS: A group of 205 children living in Kazalinsk, close to the Aral Sea, and a group of 187 children living in Zhanakorgan, far from the Aral Sea, were examined by means of random urine samples. Both urinary N-acetyl-beta-D-glucosaminidase (NAG; U/mmol Cr) and beta2 microglobulin (BMG; microg/mmol Cr) were calculated for each subject. RESULTS: Mean urinary NAG and BMG were both significantly higher in Kazalinsk than in Zhanakorgan (NAG: 0.77 (0.58) and 0.62 (0.37) U/mmol Cr; BMG: 41.8 (54.8) and 22.5 (20.4) microg/mmol Cr, respectively; mean (SD), p < 0.01). The number of children with abnormal values of NAG (>1.5 U/mmol Cr) was significantly more prevalent in Kazalinsk than in Zhanakorgan (7.9% and 2.6%, respectively, p < 0.05). CONCLUSION: Renal tubular function of children around the Aral Sea region is profoundly impaired. This should be taken into account when considering the health problems of this area.     

Effect of CYP2D6 genotypes on the metabolism of haloperidol in a Japanese psychiatric population.

We investigated the effect of CYP2D6 genotypes on plasma levels of haloperidol (HAL) and reduced haloperidol (RHAL) in 88 Japanese schizophrenic inpatients being treated with HAL. Some subjects carrying CYP2D6*5 allele (CYP2D6*1/CYP2D6*5, CYP2D6*5/CYP2D6*10) showed extremely high concentrations of both HAL and RHAL, and the groups with CYP2D6*5 allele seemed to have higher plasma concentrations of HAL (1.14+/-0.69 ng/ml/mg) and RHAL (1.10+/-1.05 ng/ml/mg) than the other groups. Among those without CYP2D6*5 allele, there were no significant differences in plasma concentrations of HAL and RHAL between those without CYP2D6*10 allele (HAL=0.68+/-0.31 ng/ml/mg, RHAL=0.28+/-0.37 ng/ml/mg), those with one CYP2D6*10 (HAL=0.70+/-0.23 ng/ml/mg, RHAL=0.31+/-0.16 ng/ml/mg) and those with two CYP2D6*10 alleles (HAL=0.69+/-0.14 ng/ml/mg, RHAL=0.40+/-0.09 ng/ml/mg), although there was a tendency of higher plasma concentration of RHAL in those with two CYP2D6*10 alleles. At a lower daily dosage of HAL (<10 mg/day), the subjects with two or one CYP2D6*10 allele(s) showed significantly higher plasma concentrations of RHAL (0.43+/-0.23 ng/ml/mg, 0.34+/-0.16 ng/ml/mg) than those without CYP2D6*10 allele (0.18+/-0.16 ng/ml/mg). The results of this study indicate that CYP2D6*10 allele plays significant but modest role in HAL metabolism in Japanese; nevertheless, we should not lump CYP2D6*10 allele with CYP2D6*5 allele because these two mutated alleles seem to have different impacts in the metabolism of HAL.     

Effects of antihistamines,ebastine and terfenadine,on electrocardiogram in conscious dogs and cats

The purpose of this study was to evaluate the effects of ebastine and terfenadine on the electrocardiogram of conscious dogs and cats. In dogs, terfenadine at oral doses of 30 mg/kg twice a day for 7 days prolonged the electrocardiographic QT interval and the corrected QT (QTc) interval on the seventh day, whereas the drug did not affect these parameters on the first day. Plasma concentrations of terfenadine and its active metabolite, fexofenadine, reached 306 and 8,541 ng/mL, respectively, on the seventh day. Ebastine at oral doses of 30 and 100 mg/kg once a day for 7 days was without effect on the QT and QTc intervals, whereas the drug slightly shortened the RR interval. On the seventh day following the dose of 100 mg/kg, plasma concentrations of ebastine and its active metabolite, carebastine, reached 36 and 1,939 ng/mL, respectively. In conscious cats, terfenadine at oral doses of 30 mg/kg twice a day for 7 days prolonged the QT and QTc intervals, QRS duration, JT and the corrected JT intervals. Unexpectedly, terfenadine induced ventricular tachyarrhythmia and premature beats. On the other hand, ebastine at oral doses of 100 mg/kg once a day for 7 days was without effect on the electrocardiographic parameters in cats. These results suggest that the electrocardiographic changes indicative of the proarrhythmic potential of terfenadine can be evaluated in conscious dogs and especially in conscious cats by repeated oral administration, and that ebastine does not induce such changes. 58:209–217, 2003. © 2003 Wiley‐Liss, Inc.     

Regulation of p27 by S-phase kinase-associated protein 2 is associated with aggressiveness in non-small-cell lung cancer.

PURPOSE: The F-box protein S-phase kinase-associated protein 2 (Skp2) is one of the positive regulators of the cell cycle that promote ubiquitin-mediated proteolysis of the cyclin-dependent kinase inhibitor p27. In this study, we investigated the significance of Skp2 expression in human non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Clinicopathologic features and immunohistochemical expression of Skp2 and p27 proteins were studied in 138 patients with NSCLC. Survival analyses were performed using the Kaplan-Meier method and the Cox regression model. To analyze the role of Skp2 in vitro, NSCLC cells were transfected with an Skp2-expressing vector or small interfering RNA. RESULTS: Skp2 was overexpressed in males, smokers, patients with squamous cell carcinomas, and patients with poorly differentiated cancers (P = .034, < .0001, < .0001, and .002, respectively). The multivariant analysis revealed that Skp2 expression is an independent prognostic factor for survival in NSCLC. An inverse relationship of Skp2 with p27 expression was observed (P = .012), and patients with both a higher expression of Skp2 and a lower expression of p27 showed a significantly unfavorable prognosis (P = .0002). In vitro ectopic expression of Skp2 in NSCLC cells reduced the protein level of p27. Conversely, induction of Skp2 siRNA increased the protein level of p27, leading to growth inhibition in NSCLC cells. CONCLUSION: Skp2 overexpression is closely associated with the suppression of p27 and the aggressiveness in NSCLC. It also could be a therapeutic target in NSCLC.