Endovascular treatment for poorest-grade subarachnoid hemorrhage in the acute stage: has the outcome been improved?

OBJECTIVE: Patients with poor-grade subarachnoid hemorrhage (SAH) have been considered good candidates for endovascular treatment. The results of treatment of Grade V SAH, the poorest grade, however, have not been fully elucidated. METHODS: The clinical characteristics and outcome parameters of 22 World Federation of Neurosurgical Societies Grade V SAH patients treated endovascularly in the acute stage between 1998 and 2000 are summarized and compared with those of 18 Grade V SAH patients treated conservatively between 1995 and 1997. RESULTS: Among the 22 patients treated endovascularly, 8 patients (36.4%) survived. The rate was significantly higher than that of the 18 patients treated conservatively (5.6%), only one of whom survived. The favorable outcome rate, however, was not significantly different between the two groups (4.5% versus 6.0%). Subdivision of both treatment groups according to Glasgow Coma Scale (GCS) score showed that the improved survival among those treated endovascularly was attributable to the improved survival in those with a preprocedural GCS score of 6 but not of 4 or 5. CONCLUSION: Endovascular treatment of the 22 World Federation of Neurosurgical Societies Grade V SAH patients improved their survival rate but not their favorable outcome rate in comparison with conservative treatment. Further accumulation of clinical data is essential to determine whether endovascular treatment can improve the functional outcome of those with GCS scores of 6 and whether there is no role for endovascular treatment in those with GCS scores of 4 or 5.     

Surgery of the liver and pancreas in Japan--message to the special symposium commemorating Dr. Ichio Honjo

About half a century ago, Ichio Honjo performed successful right hepatic lobectomy following ligation of the right hepatic artery and the right branch of the portal vein. That was the world's first successful case of right hepatic lobectomy with preliminary hilar ligation of the right branches of both the hepatic artery and portal vein. In the same year, Honjo carried out a total pancreatectomy for pancreatic cancer for the first time in Japan. Since then, marked progress in the surgical fields of the liver and pancreas has been made and appear to have nearly reached the pinnacle. Surgeons in the late half of the 20th century attempted to extend operative interventions and expand surgical fields while devoting themselves to treating incurable diseases. Therefore the period may be called the "challenging era." We are entering the era of evaluation and selection of the procedures most suitable to both the disease stage and each individual patient.     

Three-dimensional reconstruction of biliary tract using spiral computed tomography for laparoscopic cholecystectomy

To increase the safety of laparoscopic cholecystectomy, we have analyzed the biliary tract in a three-dimensional fashion. The union of the biliary ducts was studied in 50 patients using spiral computed tomography (CT) after intravenous infusion cholangiography. Depending on the union and course of the cystic duct to the common bile duct, cystic duct anatomy was classified into six categories: ipsilateral gallbladder side (type I) and contralateral side with anterior course (type II); contralateral side with posterior course (type III); intrahepatic side (type IV); intrapancreatic side (type V); and unclassified (type VI). The length of the cystic duct was also determined. The cystic duct was identified in 42 cases (84%); 30 cases (60%) were type I, 9 cases (18%) type III, and a single case (2%) of types II, IV and V, respectively. The length of the cystic duct was < or =2 cm in 30 cases that had a shorter operating time compared to 12 cases with a cystic duct <2 cm (p <0.01). In conclusion, three-dimensional reconstruction of the cystic duct anatomy using spiral CT provides simple classification of bile duct anatomy, and this preoperative information may increase the safety of laparoscopic cholecystectomy.     

Feasibility of Induction Chemotherapy Using Bronchial Arterial Infusion for Locally Advanced Non-Small Cell Lung Cancer: A Pilot Study

Purpose: We examined the feasibility and effectiveness of bronchial arterial infusion (BAI) as induction chemotherapy before surgery for locally advanced non-small cell lung cancer (NSCLC). Methods: Eighteen patients with locally advanced NSCLC were given BAI consisting of cis-diamminedichloroplatinum (CDDP) (50–100 mg/m²) as induction chemotherapy before surgery (induction BAI). Six patients with clinical stage IIIA cancer had bulky N2 metastatic lymph nodes, and 12 patients with clinical stage IIIB cancer had T4 disease. Results: Of the 18 patients, 12 (67%) showed a partial response to the BAI therapy. Standard pulmonary resection was performed in 5 patients, pulmonary resection with the combined resection of adjacent organs was performed in 10 patients, and pulmonary resection with carinal resection and reconstruction was performed in 3 patients. Complete resection was possible in 14 patients (78%). There were no serious BAI therapy-related complications or postoperative deaths. The 5-year survival rate of the 18 patients was 35.7% and the median survival time (MST) was 19.4 months. Survival was better when complete resection was achieved after the induction BAI, especially in patients with stage IIIB (T4) disease. Conclusion: Based on our preliminary findings, BAI with CDDP as induction chemotherapy is feasible and may be an effective therapeutic modality for locally advanced NSCLC. Received: July 26, 2001 / Accepted: March 5, 2002     

High metabolic function of primary human and porcine hepatocytes in a polyurethane foam/spheroid culture system in plasma from patients with fulminant hepatic failure

It has been demonstrated that plasma from patients with fulminant hepatic failure (FHF) interferes extensively with cellular function. We placed primary human and primary porcine hepatocytes in a polyurethane foam (PUF)/spheroid culture system and compared the metabolic functions in the plasma of patients with FHF in a 24-h stationary culture to those in a monolayer culture. The PUF/spheroid culture system using primary human and primary porcine hepatocytes significantly decreased ammonia content during 28-day culture. Fisher's ratio significantly increased at culture days 3 and 7. Tauroursodeoxycholic acid significantly increased and glycochenodeoxycholic acid and taurochenodeoxycholic acid decreased in the FHF patients' plasma at culture day 3. During at least a 24-h culture in the FHF patients' plasma, metabolic functions of primary human and primary porcine hepatocytes were almost identical. The present results indicate that the PUF/spheroid culture system using primary human or primary porcine hepatocytes demonstrated more advantageous metabolic functions in the plasma from patients with FHF than the monolayer culture.     

Pharmacokinetic interaction between TAK-044, a new endothelin antagonist,and ciclosporin in rats

The pharmacokinetic interaction between TAK-044 (cyclo[D-alpha-aspartyl-3-[(4-phenylpiperazin-1-yl)carbonyl]-L-alanyl-L- alpha-aspartyl-D-2-(2-thienyl) glycyl-L-leucyl-D-tryptophyl] disodium, CAS 157380-72-8) and ciclosporin (CAS 59865-13-3) was investigated after concomitant intravenous (i.v.) administration in rats. After i.v. administration of 14C-labeled TAK-044 ([14C]TAK-044 alone at a dose of 3 mg/kg, the radioactivity concentration in the plasma was 1.65 micrograms/ml at 5 min and decreased biphasically with half-lives of 0.09 h and 0.39 h. AUC0-1 h was 0.38 microgram.h/ml. The pharmacokinetics of [14C]TAK-044 were affected dose-dependently by coadministration with ciclosporin. The AUC value for [14C]TAK-044 was increased 5- and 14-fold by the coadministration with cyclosporin at doses of 3 and 10 mg/kg, respectively. On the other hand, TAK-044 (3 and 10 mg/kg) did not change the pharmacokinetic parameters for ciclosporin (3 mg/kg). Biliary excretion is the major elimination route for both TAK-044 and cyclosporin. Ciclosporin delayed biliary excretion of [14C]TAK-044 in a dose-dependent manner, which might be due to inhibition of process(es) of hepato-biliary excretion of TAK-044. In conclusion, the AUC values for TAK-044 in rats are increased dose-dependently by coadministration with ciclosporin. Therefore, it may be necessary to adjust the dosage of the TAK-044 in combination with ciclosporin in the course of the first clinical trials.     

Helicobacter pylori may survive ampicillin treatment in the remnant stomach

Helicobacter pylori (H. pylori) is a Gram-negative curved rod-like or spiral bacterium that chronically infects the human gastric mucosa, and is a major risk factor for gastritis, gastric and duodenal ulcer and adenocarcinoma of the stomach. After partial gastrectomy, some patients may have persistent H. pylori infection for five years or more. In this study, we detected three bacteria, i.e., Klebsiella pneumoniae, Enterobacter aerogenes, and Escherichia coli, in the gastric juice of patients with a remnant stomach. Some of these bacteria produced beta-lactamase. These findings are potentially important since such bacteria could provide H. pylori with the chance to acquire drug resistance and to transfer drug resistance genes. This could be one reason why H. pylori is difficult to eradicate in the remnant stomach.     

Time- and dose-dependent effect of fosfomycin on suppression of infection-induced endotoxin shock in mice

Therapeutic effects of fosfomycin (FOF) and imipenem (IPM) were investigated in a novel model for endotoxin shock that was caused by intraperitoneal (i.p.) infection with 10(8) colony forming units of attenuated Salmonella typhimurium. Acute lethal shock was observed in BALB/c and ddY but not in lipopolysaccharide (LPS)-nonresponder BALB/lps(d) mice. Effects of FOF, but not its enantiomer, and IPM were dose- and time-dependent, since therapeutic efficacy was demonstrated in mice injected i.p. or orally at doses of more than 20 mg/kg 15 min before or 1 h after infection. Treatment with FOF 1 h postinfection (p.i.) resulted in significant decreases in bacterial numbers in spleen and liver, suggesting that the antimicrobial activity of FOF seems to closely correlate to suppression of infection-induced lethal shock. Regarding coagulation systems, FOF inhibited increase in the prothrombin time but upregulated fibrinogen concentration. Plasma levels of LPS released from bacilli were significantly higher in FOF- than IPM-treated mice and infection controls, but both antibiotics showed similar efficacy in protection.     

Anxiety in school refusal children with indefinite complaints: psychological estimation using State-Trait Anxiety Inventory and therapy by serotonin reuptake inhibitors

Using State-Trait Anxiety Inventory (STAI) we examined 13 junior high school students with school refusal and indefinite complaints. Significant increase of the anxiety levels was higher in these children than in the control group. Serotonin reuptake inhibitors (SSRIs) were administered to 19 elementary and junior high school students with school refusal and indefinite complaints. The indefinite symptoms improved markedly in 2 children, moderately in 11, and mildly in 6. We conclude that high anxiety may cause indefinite symptoms in children with school refusal and that the treatment of indefinite symptoms with SSRI is an effective supportive therapy.     

MEGF1/fat2 proteins containing extraordinarily large extracellular domains are localized to thin parallel fibers of cerebellar granule cells

The MEGF1 (protein 1 with multiple EGF-like domains) gene, which was identified using motif-trap screening, encodes an extraordinarily large protein containing two EGF-like and 34 cadherin motifs. In situ hybridization analysis revealed that the MEGF1 gene was specifically expressed in granule cells of the cerebellum. Interestingly, in the developing cerebellum, granule cells in the inner external germinal layer and migrating granule cells expressed MEGF1 mRNA, whereas proliferating cells in the outer external germinal layer did not express MEGF1 mRNA. Expression levels in the internal granule cell layer peaked during the third postnatal week and remained considerably high in the adult cerebellum. MEGF1 protein was detected in only the cerebellum as a single 480-kDa band by immunoblot analyses using polyclonal antibodies against either the N-terminal or the C-terminal region of MEGF1 protein. Using light and electron microscopic immunocytochemistry, specific immunostaining of the MEGF1 protein was observed in the molecular layer of the cerebellum, suggesting that MEGF1 protein was localized in the parallel fibers of cerebellar granule cells. This was corroborated by results from experiments using primary dispersed cultures of cerebellar granule cells and cerebellar microexplant cultures. The homophilic interaction of MEGF1 proteins was confirmed with both a cell aggregation assay and an in vitro copurification assay. Based on these results, a novel function of the enormous protocadherins in cerebellar development, namely, the modulation of the extracellular space surrounding parallel fibers during development, was proposed.