Trends in the serovar and antimicrobial resistance in clinical isolates of Salmonella enterica from cattle and pigs between 2002 and 2016 in Japan.

AIMS: Given the significance of Salmonella enterica in both human and animal health, and a recent global dissemination of Salmonella 4,[5],12:i:-, changes in the prevalent serovars and antimicrobial resistance in clinical isolates of Salmonella from cattle and pigs were investigated in Japan. METHODS AND RESULTS: The serovars and antimicrobial susceptibilities of 1605 Salmonella enterica isolated from cattle (n = 894) and swine (n = 711) between 2002 and 2016 were examined. The most common serovar among all samples was Salmonella Typhimurium. However, its monophasic variant with antigenic structure S. 4,[5],12:i:-, which was first detected in cattle in 2006 and swine in 2010, has been rapidly increasing in incidence and resistance. Resistance rates to cefotaxime and ciprofloxacin were generally low (<10% in the cattle isolates and <5% in the swine isolates); however, isolates resistant to more than five antimicrobials, which often include these antimicrobials, were recently detected in Salmonella Dublin, S. 4,[5],12:i:-, S. Typhimurium, Salmonella Newport, Salmonella Choleraesuis and Salmonella 6,7:c:-. Among them, two S. 4,[5],12:i:- isolates possessed extended-spectrum ß-lactamase-encoding genes; blaSHV-12 or blaCTX-M-55 , respectively, while all the five S. Typhimurium isolates possessed AmpC-type ß-lactamase gene of blaCMY-2 . CONCLUSIONS: S. 4,[5],12:i:- has been rapidly increasing and exhibiting a remarkable change in antimicrobial resistance in Japan. Considering certain serovars are characterized by multidrug resistance including medically important antimicrobials, continuous monitoring and appropriate measures are required to protect public health and veterinary husbandry. SIGNIFICANCE AND IMPACT OF THE STUDY: This study presents a trend in the serovars and antimicrobial resistance in clinical isolates of Salmonella from cattle and pigs in Japan, and showed that there were certain types of Salmonella serovars depending on the animal origin which needs more attention.

Population pharmacokinetics and pharmacodynamics of mycophenolic acid using the prospective data in patients undergoing hematopoietic stem cell transplantation.

Mycophenolate mofetil (MMF), a prodrug of mycophenolic acid (MPA), is used to suppress GvHD in patients undergoing hematopoietic stem cell transplantation (HCT). The purpose of this study was to construct a population pharmacokinetic and pharmacodynamic model in HCT patients for individualized MPA therapy. Blood samples were obtained from 49 HCT patients after starting MMF therapy. Population pharmacokinetic and pharmacodynamic parameters were obtained using the program NONMEM. MPA was described via a one-compartment model with a first-order elimination, and 30.9% of MPA glucuronide (MPAG) was found in the enterohepatic circulation. Inosine-5'-monophosphate dehydrogenase (IMPDH) activity was modeled as a maximal inhibitory model with a half-maximal inhibitory concentration (IC50) of 3.59 µg/mL against MPA concentrations. Simulations based on the obtained pharmacokinetic and pharmacodynamic parameters revealed that decreased creatinine clearance increases the MPAG concentration followed by an increased MPA concentration; therefore, IMPDH activity decreases. Diarrhea decreases the enterohepatic circulation of MPAG and consequently reduces MPA concentration. The IC50 for MPA exhibited a positive association with C-reactive protein. Dosage adjustment based on plasma MPA concentration is required especially for patients with renal dysfunction and/or diarrhea.

In not only vertebroplasty but also kyphoplasty, the resolution of vertebral deformities depends on vertebral mobility.

BACKGROUND AND PURPOSE: It has not been clarified whether the postoperative resolution of vertebral deformities achieved by KP are superior to those achieved by VP. We compared the outcomes of KP and VP, taking into account the presence of vertebral mobility, to determine whether the balloon inflation in KP may contribute to postoperative resolution of the vertebral deformities in patients with VCFs. MATERIALS AND METHODS: The subjects had 34 vertebral bodies treated by VP, and 43 vertebral bodies treated by KP. In all patients, preoperative dynamic imaging was performed to assess the presence of vertebral mobility. First, the vertebral height restoration and kyphotic change were compared between the VP and KP groups. Then, the patients were further divided into 2 groups on the basis of the presence of vertebral mobility, and they were compared within and between the VP and KP groups in relation to the presence of vertebral mobility. RESULTS: Overall, no significant differences were observed in either the vertebral height restoration or kyphotic change between the VP and KP groups (P > .20). Preoperative dynamic imaging identified 19 vertebral bodies each with vertebral mobility in the VP (56%) and KP groups (44%) (P = .21). Within the VP and KP groups, the vertebral height restoration and kyphotic changes were significantly better in patients with vertebral mobility than in those without (P < .01). There were no significant differences between the 2 treatment groups after adjustment for the presence of vertebral mobility (P > .30). CONCLUSIONS: In both the VP and KP groups, the vertebral height restoration and kyphotic change largely depended on the preoperative vertebral mobility. The use of the balloon itself contributed little to resolution of the vertebral deformities.

Validity of intervertebral bone cement infusion for painful vertebral compression fractures based on the presence of vertebral mobility.

BACKGROUND AND PURPOSE: It is uncertain whether analgesic effects of vertebroplasty in patients with painful VCF are actually attributable to intervertebral cement infusion. This study aims to assess the validity of cement infusion performed for pain relief based on the presence or absence of pseudoarthrosis. MATERIALS AND METHODS: We compared therapeutic effects between PVP and vertebral perforation without bone cement infusion in patients with painful VCF. The subjects were 64 patients undergoing PVP (PVP group) and 67 undergoing vertebral perforation (perforation group). In all patients, preoperative dynamic radiography was performed to assess the presence of vertebral mobility. Patients were classified into 2 groups, those with and those without vertebral mobility, and changes in VAS and ADL scores before and after surgery were compared between the PVP and perforation groups. RESULTS: Regarding patients with vertebral mobility, VAS improved during the 3 months immediately after surgery in the PVP group compared with the perforation group (P < .05). Although no significant difference in postoperative ADL scores was observed between the 2 treatment groups, the scores 3 months after surgery were better in the PVP group than in the perforation group. Meanwhile, in the subgroup of patients without vertebral mobility, both treatments produced marked pain relief, but the difference was not significant (P > .05). Moreover, there was no difference in ADL scores between the 2 treatment groups. CONCLUSIONS: Intervertebral cement infusion exerts analgesic effects in patients with VCF with pseudoarthrosis. However, in those without vertebral mobility, the analgesic effects of vertebroplasty are the same regardless of bone cement infusion.

Cerebral blood flow and metabolism measurement using positron emission tomography before and during internal carotid artery test occlusions: feasibility of rapid quantitative measurement of CBF and OEF/CMRO(2).

Balloon test occlusion (BTO) of the internal carotid artery (ICA) combined with cerebral blood flow (CBF) study is a sensitive test for predicting the outcome of permanent ICA occlusion. However, false negative results sometimes occur using single photon emission tomography (SPECT). We have recently developed a rapid positron emission tomography (PET) protocol that measures not only the CBF but also the cerebral oxygen metabolism before and during BTO in succession. We measured acute changes in regional CBF and OEF/CMRO(2) before and during BTO in three cases with large or giant cerebral aneurysms using the rapid PET protocol. Although no patients showed ischemic symptoms during BTO, PET studies exhibited mildly to moderately decreased CBF (9∼34%) compared to the values obtained before BTO in all cases. The average OEF during BTO was significantly increased (21% and 43%) than that of before BTO in two cases. The two cases were considered to be non-tolerant for permanent ICA occlusion and treated without ICA sacrifice. Measurement of the CBF and OEF/CMRO(2) using a rapid PET protocol before and during BTO is feasible and can be used for accurate assessment of tolerance prediction in ICA occlusion.

Comparative study of percutaneous vertebral body perforation and vertebroplasty for the treatment of painful vertebral compression fractures.

BACKGROUND AND PURPOSE: Percutaneous vertebral body perforation is a new technique for treating painful VCFs. Herein, we compare the therapeutic effect of vertebral perforation and conventional vertebroplasty for treating VCFs. MATERIALS AND METHODS: One hundred eight patients with single painful VCFs were assigned to undergo vertebral perforation (perforation group) or vertebroplasty (PVP group). Clinical outcomes were assessed by using the VAS. The associations of analgesic effect and clinical factors were also analyzed by multivariate regression. Plain radiographs were used to quantify the progression of vertebral body compression after surgery and to evaluate cement leakage and new vertebral fractures. The median follow-up time was 10 months. RESULTS: Baseline characteristics were similar in the 2 groups. No factors correlated with analgesic effects in the PVP group. The analgesic effect of vertebral perforation was, however, related to the preoperative severity of vertebral compression and was low in patients with severe deformity (P < .05). Among patients with preoperative vertebral percentage of compression below 30%, there were no significant differences between the 2 groups in analgesic effect at any postoperative intervals. Progression of vertebral compression after surgery occurred in 22.2% and 16.0% of treated vertebrae in the perforation and PVP groups, respectively (P = .38). Respectively, 3.7% and 20.0% of the perforation and PVP groups had new postoperative fractures during follow-up (P < .05). There were no other complications. CONCLUSIONS: Vertebral perforation was safe and effective for painful VCFs with slight compression. However, vertebroplasty should be considered for patients with marked vertebral body compression.

Body mass-based exercise in middle-aged and older women.

The present study examined whether the degree to which muscle strength is improved by a body mass-based home exercise program in middle-aged and older women depends on the force-generating capabilities of the muscles prior to the intervention. 75 women (53-76 years) voluntarily participated in a circuit training program consisting of 5 exercises (16 repetitions/exercise, 2 or 3 circuits/day) using only body mass as resistance for 3 months. The subjects performed the training program 6 days a week in their own home and once a week in a local gym. Before and after intervention, isometric torques during maximal voluntary knee extension (KET) and plantar flexion (PFT) were determined and expressed relative to body mass (KET/BM and PFT/BM, respectively). KET/BM and PFT/BM increased significantly after intervention, and their relative changes were negatively correlated to the absolute values before intervention. Most of the subjects whose KET/BM and PFT/BM values before intervention were greater than 2.8 Nm/kg and 1.7 Nm/kg, respectively, did not show increases in strength after intervention. Thus, although body mass-based exercise at home is effective in improving lower limb strength in middle-aged and older women, the magnitude of the improvement is influenced by the force-generating capability before intervention.

Molecular diversity of Photobacterium damselae ssp. piscicida from cultured amberjacks (Seriola spp.) in Japan by pulsed-field gel electrophoresis and plasmid profiles.

AIMS: This study deals with a pulsed-field gel electrophoresis (PFGE) for discriminating between the genetic variants of Photobacterium damselae ssp. piscicida, and characterizing of Japanese field isolates by PFGE together with plasmid profiles and antimicrobial resistances. METHODS AND RESULTS: A total of 74 field isolates from cultured Japanese amberjacks were used for PFGE. SmaI and NotI enabled to clearly differentiate strains and we obtained 24 of combined PFGE profiles which were distinct from those of classical Japanese and USA reference strains, and classified them into three groups (Ia-Ic). By plasmid size, we could classify these field isolates into three plasmid types, pA-pC. The predominant PFGE-type Ia was closely associated with plasmid-type pA, and Ib showed a moderate association with pB. Ic was closely associated with pC, and multiresistant isolates were not observed in this type. Whole-genomic variations were also observed between isolates having identical detection areas, fish species and detection-date by PFGE. CONCLUSION: Molecular diversity of P. damselae ssp. piscicida could be detected by PFGE, and some relations among the PFGE-type, plasmid-type and antimicrobial resistances were observed in Japanese field isolates. SIGNIFICANCE AND IMPACT OF THE STUDY: This study indicated that some genetic transition might have occurred in P. damselae ssp. piscicida around the Japanese seas, and PFGE can be a valuable tool for the epidemiological study of this highly homogeneous subspecies.

Characterization of Lactococcus garvieae isolated from radish and broccoli sprouts that exhibited a KG+ phenotype, lack of virulence and absence of a capsule.

AIMS: To identify Lactococcus garvieae isolates from radish and broccoli sprouts and compare them with virulent and less virulent mutant strains obtained from yellowtails with regard to KG phenotype, presence of a capsule and virulence towards yellowtails and mice. METHODS AND RESULTS: Comparative 16S rRNA gene sequence analysis of six isolates obtained from radish and broccoli sprouts indicated that they were L. garvieae (similarity >99%). They were compared with KG9502, Lg2 and ATCC49156 strains obtained from yellowtails. A less virulent mutant strain Lg2-S was obtained by Lg2 subculture. Biochemical characterization of the six strains resembled that of KG9502, Lg2, ATCC49156 and Lg2-S, except for saccharose and tagatose acidification and the presence of hippuricase. These six strains were nonpathogenic towards yellowtails and mice, nonsusceptible to bacteriophages and demonstrated heterogeneity on pulsed-field gel electrophoresis analysis. Using transmission electron microscopy, a capsule was observed in KG9502 and Lg2 but not in ATCC49156 and Lg2-S. CONCLUSIONS: We isolated L. garvieae strains that lacked pathogenicity towards yellowtails and mice from radish and broccoli sprouts; these were noncapsulated and exhibited KG(+) phenotype. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first documentation of L. garvieae isolated from terrestrial plants. These isolates exhibited genetic diversity; however, they were noncapsulated and nonpathogenic towards yellowtails and mice.

Intracerebral Hemorrhage after Carotid Artery Stenting without Evidence of Hyperperfusion in Positron Emission Tomography.

SUMMARY: A 75-year-old man with a recent history of transient left hemiparesis and dysarthria was referred to our hospital. Angiography showed right internal carotid artery (ICA) occlusion and left ICA 89% stenosis. Positron emission tomography (PET) showed decreased cerebral blood flow (CBF), and increased oxygen extraction fraction (OEF) and cerebral blood volume (CBV) in the right hemisphere. In the left hemisphere, CBV was increased, but CBF and OEF remained normal. One month after the transient ischemic attack, left carotid artery stenting (CAS) was performed without complications. Diffusion-weighted magnetic resonance imaging (MRI) on the day after CAS showed no fresh ischemic lesion. PET on the second day after CAS showed increased CBF and decreased OEF and CBV in the right hemisphere as compared with those before CAS. In the left hemisphere, decreased CBV was observed and CBF was slightly increased as compared with those before CAS. The postoperative course was uneventful, but on the fifth day after CAS, the patient suddenly showed a focal seizure and right motor weakness. Emergency computed tomography scanning showed massive intracranial hemorrhage with severe brain edema in the left hemisphere. Although CBF study is useful to predict the hyperperfusion syndrome, we cannot disregard the possibility of intracerebral hemorrhage after CAS for carotid artery stenosis when there is no evidence of hyperperfusion on postoperative CBF study.

Differences between Lactococcus garvieae isolated from the genus Seriola in Japan and those isolated from other animals (trout, terrestrial animals from Europe) with regard to pathogenicity, phage susceptibility and genetic characterization.

AIMS: To clarify the epidemiological relationship between Lactococcus garvieae isolates from the Seriola in Japan and isolates from other animals. METHODS AND RESULTS: A total of 32 isolates obtained from aquatic (the genus Seriola and trout) and terrestrial animals (cow, pig, cat, dog and horse) was used to evaluate its pathogenicity to yellowtail and mouse, phenotype (KG+ and KG-), its susceptibility to three bacteriophages and the pattern of pulsed field gel electrophoresis (PFGE). Lactococcus garvieae isolated from Seriola showed strong pathogenicity to yellowtail, while isolates from trout showed weak pathogenicity and those obtained from terrestrial animals showed no distinct pathogenicity. Only, the isolates from the genus Seriola in Japan showed susceptibility to the bacteriophages. The results of PFGE pattern indicate that the isolates obtained from the Seriola predict homogeneity, while there is no similarity among the isolates obtained from different animals. CONCLUSION: This experiment indicates that L. garvieae isolated from Seriola in Japan appears to be very different from the isolates obtained from other animals, and the isolates prevalent among the genus Seriola in Japan might be homogeneous. SIGNIFICANCE AND IMPACT OF THE STUDY: This study suggests that a particular genetic group that has specially adapted and acquired virulence toward yellowtail were prevalent among the genus Seriola in Japan.

Drug resistance and random amplified polymorphic DNA analysis of Photobacterium damselae ssp. piscicida isolates from cultured Seriola (yellowtail, amberjack and kingfish) in Japan.

AIMS: To investigate the antimicrobial susceptibility and genetic characteristics of Photobacterium damselae ssp. piscicida isolates obtained from cultured Seriola in Japan. METHODS AND RESULTS: Minimal inhibitory concentrations of 14 antimicrobials for 74 isolates from Seriola in Japan in 2002 were determined. Isolates showed high frequencies of resistance to sulfamonomethoxine (SMMX) (97.3%), oxytetracycline (OTC) (77.0%), flumequine (FMQ) (77.0%), chloramphenicol (CP) (75.7%), kanamycin (KM) (63.5%) and oxolinic acid (OA) (62.0%), but low to ampicillin (ABPC) (2.8%). All isolates were susceptible to bicozamycin (BCM), fosfomycin (FOM) and florfenicol (FF). Of these isolates, 45 (60.8%) showed same resistance pattern (SMMX-OTC-FMQ-OA-CP-KM). In random amplified polymorphic DNA (RAPD) analysis, no difference was observed among our 74 field isolates and ATCC51736 isolated from Seriola in 1974 in Japan, but different from ATCC 17911 isolated from white perch in USA. CONCLUSIONS: FF, BCM, FOM and ABPC were useful antimicrobials for treating pseudotuberculosis. However, the frequency of multidrug resistance was high. RAPD analysis showed homogeneity of isolates from Seriola in Japan. SIGNIFICANCE AND IMPACT OF THE STUDY: This study demonstrates that some antimicrobials were still useful for treating pseudotuberculosis and that P. damselae ssp. piscicida strains of same origin might have spread among Seriola in Japan since 1974.

A national surveillance of Shiga toxin-producing Escherichia coli in food-producing animals in Japan.

To assess the public health risk, the prevalence and anti-microbial resistance of Shiga toxin-producing Escherichia coli (STEC) among food-producing animals were studied throughout Japan. Faecal samples were collected from healthy animals of 272 cattle, 179 pigs, and 158 broilers on 596 farms in all 47 Japanese prefectures. STEC were isolated from 62 (23%) cattle and 32 (14%) pig samples but from no chicken samples. Of the bovine isolates, 19 belonged to serotypes frequently implicated in human disease (O157:H7/non-motile (NM)/H not typeable, O26:NM/H11/H21/H not typeable, O113:H21, and O145:NM). The eae genes were observed in 37% of bovine isolates; among them one O145:NM and all four O157 isolates possessed eae-gamma1, and one O145:NM, one O103:H11, and all five O26 isolates possessed eae-beta1 gene. Among the swine isolates, stx2e were dominant, and serotypes frequently implicated in human diseases or eae-positive isolates were not observed. Bovine isolates showed less anti-microbial resistance, but six isolates of 26:NM/H11 and O145:NM were multi-resistant and may need careful monitoring. Swine isolates showed various resistance patterns; chloramphenicol resistance patterns were more common than in bovine isolates. This first national study of STEC in the Japanese veterinary field should aid our understanding of Japan's STEC status.

Drug resistance and pulsed-field gel electrophoresis patterns of Lactococcus garvieae isolates from cultured Seriola (yellowtail, amberjack and kingfish) in Japan.

AIMS: To investigate the existing antimicrobial susceptibility and genetic characteristics of Lactococcus garvieae isolates from cultured Seriola in Japan. METHODS AND RESULTS: Minimum inhibitory concentrations (MICs) of 14 antimicrobial agents for 170 isolates were determined using the agar dilution method. Seventy-five isolates (44.1%) were simultaneously resistant to erythromycin (EM) (MIC>or=2 microg ml-1), lincomycin (LCM) (MIC>or=128 microg ml-1) and oxytetracycline (OTC) (MIC>or=4 microg ml-1). Resistance to EM was grouped as intermediate- and high-level resistant by MIC values. All resistant isolates possessed ermB and tet(S) genes. The number of different bands between pulsed-field gel electrophoresis patterns of 25 isolates and two ATCC strains (isolated in 1974), determined using two enzymes (ApaI and SmaI), did not exceed 3. CONCLUSIONS: The present resistance pattern observed with ermB and tet(S) is similar to that observed in previous reports. Moreover, the genetic characteristics of L. garvieae isolates from a wide area in Japan in 2002 and ATCC strains were closely related. SIGNIFICANCE AND IMPACT OF THE STUDY: This study suggests that EM-, LCM- and OTC-resistant isolates have been present for 15 years and that L. garvieae strains with same origin have spread among Seriola spp. in Japan since 1974.

Improvement in gastric histology following Helicobacter pylori eradication therapy in Japanese peptic ulcer patients.

We aimed to determine if successful or failed eradication of Helicobacter pylori with triple therapy causes any difference in gastric mucosal histology. Japanese H. pylori-positive patients with a healed peptic ulcer received high (n = 112) or low (n = 113) doses of triple therapy (omeprazole, amoxicillin and clarithromycin) for 1 week. Biopsies from the greater curvature of the central antrum and upper corpus were taken 6 weeks and 30 weeks after treatment completion, and gastric mucosal histology compared between successful (n = 171) and failed (n = 34) eradication groups. Morphological variables of gastritis were graded according to the updated Sydney System. Successful eradication therapy was defined as improvement in inflammation, neutrophil activity and atrophy; failed eradication therapy as improvement in inflammation and neutrophil activity only. Gastric mucosal atrophy gradually improved (in addition to improvements in inflammation and neutrophil activity) with successful eradication of H. pylori infection.

Treatment of cold injury-induced brain edema with a nonspecific matrix metalloproteinase inhibitor MMI270 in rats.

Blood-brain barrier (BBB) disruption is a critical event leading to vasogenic brain edema and secondary brain damage after cold injury-induced brain trauma. Matrix metalloproteinases (MMPs) are implicated in BBB disruption in this model. The purpose of this study was to examine the effects of MMI270, a synthetic nonspecific MMP inhibitor, on cold injury-induced brain edema in rats. Treatment with MMI270, a bolus injection at a dose of 30 mg/kg, was started immediately after the induction of cold injury and was continued at a dose of 40 mg/kg/day using an intraperitoneal osmotic minipump. At 24 hours after the cold injury, the brain water content and the BBB permeability to Evans Blue (EB) were determined. The secondary brain lesion was assessed using hematoxylin and eosin (H-E) staining at 7 days after the cold injury. Compared with the untreated control group, treatment with MMI270 significantly reduced the brain water content in the ipsilateral core and intermediate areas and protected the BBB integrity to EB in the ipsilateral core area. The secondary lesion was significantly smaller in the MMI270-treated animals compared with the untreated animals. Our results indicate that treatment with MMI270 in rats exhibits protection in acute brain edema formation and secondary brain lesion by attenuating the BBB permeability after cold injury.

Effect of hypothermia on brain edema formation following intracerebral hemorrhage in rats.

Brain edema is an important clinical complication of intracerebral hematoma (ICH). Hypothermia has been employed as an effective neuroprotective treatment on cerebral ischemia and contusional brain injuries. In this study, we attempted to evaluate the effects of mild hypothermia (35 degrees C) on brain edema formation at 48 hours after ICH in the rat. Brain hypothermia started at 6, 12 and 24 hours after the induction of hematoma (HT6; n = 6, HT12; n = 11, HT24; n = 6). Brain water contents in the basal ganglia was significantly reduced in the rats treated with mild hypothermia compared with the normothermic rats (NT; 82.0 +/- 0.04% vs. HT6; 78.6 +/- 0.09%: p < 0.01, HT12; 79.7 +/- 0.05%.: p < 0.01, HT24; 79.7 +/- 0.05%: p < 0.01). Differences in the brain water content were not significant among the hypothermic subgroups. The BBB disruption to Evan's blue was significantly reduced with hypothermia compared with the normothermic rats in the ipsilateral basal ganglia (42.3 +/- 4.0 vs. 23.0 +/- 5.2 ng/g wet tissue; p < 0.05). Hypothermic treatment tended to inhibit the accumulation of polymorphonuclear (PMN) leukocytes in the lesion compared with the normothermic treatment (0.78 +/- 0.13 vs. 0.51 +/- 0.16 deltaAbs/mg tissue). This study indicates that hypothermic treatment significantly reduces the brain edema formation after ICH in rats.

Balloon-assisted guglielmi detachable coil placement in wide-necked internal carotid-ophthalmic aneurysms: a report of four cases.

We present an endovascular technique for treating wide-necked ophthalmic aneurysms using Guglielmi detachable coils with simultaneous temporary balloon protection. Four illustrative cases of wide-necked ophthalmic aneurysms treated with Guglielmi detachable coils and a temporary balloon are presented. By blocking the parent artery with a non-detachable balloon, the coils could be safely placed in these aneurysms without herniation when the balloon was deflated. All patients exhibited embolic manifestations after the procedure, and the use of simultaneous temporary balloon protection allowed more dense intra-aneurysmal coil packing. Although this technique requires manipulation of a second microcatheter and balloon, which increases its technical difficulties and is a higher-risk procedure than the standard coil placement, it can be used for patients who are not candidates for surgery. Long-term follow-up is needed to determine the final outcome of aneurysms treated by this technique.

[Chemotherapy for gliomas based on the expression levels of drug resistant genes].

Drug resistance, which often occurs during chemotherapy, is still a great obstacle to the success of human malignancy treatment. Among many possible mechanisms of drug resistance (biological, biochemical, kinetic or pharmacological), both typical and atypical multidrug-resistance (MDR) have been extensively studied. We picked up MDR-1, MXR, MRP1, MRP2, TopoII alpha, MGMT, and GST-pi as drug-resistant gene, based on experimental data and previous reports. Expression of these genes were measured in 14 malignant glioma specimens by reverse transcription polymerase chain reaction assay. We chose anticancer drugs for each patient, based on results of drug resistant gene expression to acquire good response to drugs. Though our follow-up periods are not long enough to analyze the results of our chemotherapy, 78% (7/9) of our glioma patients who were treated with our chemotherapy are free from tumor progression. The assays, which measure the expression of drug resistant genes, are necessary to allow rapid detection of the drug-sensitivity to chemotherapy in malignant glioma patients.

Oxidative DNA damage in cultured cells and rat lungs by carcinogenic nickel compounds.

DNA damage in cultured cells and in lungs of rats induced by nickel compounds was investigated to clarify the mechanism of nickel carcinogenesis. DNA strand breaks in cultured cells exposed to nickel compounds were measured by using a pulsed field gel electrophoresis technique. Among nickel compounds (Ni(3)S(2), NiO (black), NiO (green), and NiSO(4)), only Ni(3)S(2), which is highly carcinogenic, induced lesions of both double- and single-stranded DNA in cultured human cells (Raji and HeLa cells). Treatment of cultured HeLa cells with Ni(3)S(2) (10 microg/ml) induced a 1.5-fold increase in 8-hydroxy-2'-deoxyguanosine (8-OH-dG) compared with control, whereas NiO (black), NiO (green), and NiSO(4) did not enhance the generation of 8-OH-dG. Intratracheal instillation of Ni(3)S(2), NiO(black), and NiO(green) to Wistar rats increased 8-OH-dG in the lungs significantly. NiSO(4) induced a smaller but significant increase in 8-OH-dG. Histological studies showed that all the nickel compounds used induced inflammation in lungs of the rats. Nitric oxide (NO) generation in phagocytic cells induced by Ni(3)S(2), NiO(black), and NiO(green) was examined using macrophage cell line RAW 264.7 cells. NO generation in RAW 264.7 cells stimulated with lipopolysaccharide was enhanced by all nickel particles. Two mechanisms for nickel-induced oxidative DNA damage have been proposed as follows: all the nickel compounds used induced indirect damage through inflammation, and Ni(3)S(2) also showed direct oxidative DNA damage through H(2)O(2) formation. This double action may explain relatively high carcinogenic risk of Ni(3)S(2).