Boron neutron capture therapy: Preliminary study of BNCT with sodium borocaptate (Na2B1 2H1 1SH) on glioblastoma

To plan the optimal BNCT using BSH for glioblastoma patients, the¹⁰B concentration in tumor and blood was investigated in 11newly diagnosed glioblastoma patients. All patients received 20 mg BSH/kgbody weight 2.5–16 hrs prior to tumor removal. The quantitativedistribution of ¹⁰B was determined by prompt gamma rayspectrometry and/or -track autoradiography. ¹⁰Bdistribution in tumors was heterogeneous, ± 25% of scatteringat the microscopic level, and the distribution was also heterogeneous at thetissue level. ¹⁰B concentration in blood decreased inbi-exponential decay as a function of the time after the end of theadministration. The T/B ratio showed non-exponential increase with largevariation. The maximum T/B ratio would be around 1. The tumor/normal brain(T/N) ratio of ¹⁰B concentration was 11.0 ± 3.2. The¹⁰B content in normal brain is originated in vascular¹⁰B in parenchyma, since the ¹⁰B content innormal brain to blood (N/B ratio) being compatible with the blood content inparenchyma. These values allow for BNCT, using thermal neutrons, on braintumors located less than approximately 3.3 cm in depth from the brainsurface of neutron incidence, providing that the dose on the normalendothelium is controlled to less than the tolerance limit. In ourpreliminary study of BNCT, a 31% 3-year survival was achieved overall for 16 glioblastoma patients and a 50% 2-year survival wasachieved on 8 glioblastoma patients in our recent dose escalation studybased on these data.     

Interleukin-6 and granulocytic elastase levels following laparoscopic cholecystectomy

Interleukin-6 (IL-6) levels have been shown to correlate well with the magnitude of surgical stress. Serum IL-6 and plasma granulocytic elastase levels, 24 h after surgery, were determined in 12 patients who underwent open major surgery [MS group; esophageal carcinoma (n=5), gastric carcinoma (n=3), colorectal carcinoma (n=4) 5 patients who had open cholecystectomy [OC group] and 17 patients who had laparoscopic cholecystectomy [LC group]. IL-6 levels correlated significantly with the duration of surgery (r=0.685,P < 0.01) and with intraoperative blood loss (r=0.583,P < 0.02). However, there was no significant correlation between granulocytic elastase and the duration of surgery or blood loss. Plasma IL-6 levels in the LC group (21±3 pg/ml) were significantly lower than those in the OC group (47±5 pg/ml) and the MS group (186±36pg/ml) (P<0.05;P<0.01). However, there was no significant difference in granulocytic elastase levels between the LC group (318±8g/l), the OC group (360±130 gmg/ml), and the MS group (701±344 g/l). Increased IL-6 levels correlated well with increased duration of surgery. The lower IL-6 levels following laparoscopic cholecystectomy may therefore be indicative of lower surgical stress associated with laparoscopic cholecystectomy.     

Use of the sandwich method with an ultra-high-molecular-weight polyethylene prosthesis and Marlex mesh in sternal reconstruction: Report of a case

A 52-year-old Japanese man with a slow-growing chondroma originating from the sternal bone was referred to our hospital. A subtotal resection of the sternum was performed, hereafter termed the sandwich method, and an originally designed prosthesis made from ultra-high-molecular-weight polyethylene and Marlex mesh was used for reconstruction. The postoperative course was uneventful without any symptoms due to paradoxical movement of the chest or regional abscess, and no disturbance in the movement of the upper limbs, such as a surgical sequelae, was observed.     

Expandable metallic stent treatment for malignant colorectal strictures

Four patients were treated by placement of an expandable metallic stent (two Gianturco Z-stents, two Ultraflex stents) for malignant colorectal strictures. All four patients were able to defecate after stent placement. Stent migration was recognized in one patient. Two patients suffered from tenesmus after stent placement.     

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)     

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.