Biomedical subjects

M Fujimura

Publications and source records attributed to M Fujimura.

At least 73 records · Page 4Linked to original sources

PubMed2001

Effects of carbocysteine on antigen-induced increases in cough sensitivity and bronchial responsiveness in guinea pigs.

Carbocysteine is a mucoactive drug and is being used for both acute and chronic infectious airway diseases. Although carbocysteine can repair the damage of epithelial cells caused by exposure to various agents, the effects of this agent on allergic airway diseases such as asthma and eosinophilic bronchitis with an isolated chronic cough, in both of which epithelial damage may be characteristic, is not clear. We investigated the effects of carbocysteine on antigen-induced cough hypersensitivity to inhaled capsaicin at 48 h and bronchial hyperresponsiveness to inhaled methacholine at 72 h after challenge with an aerosolized antigen in actively sensitized guinea pigs. After measuring bronchial responsiveness, we examined neutral endopeptidase (NEP) activity in the tracheal tissue. Carbocysteine (10, 30, or 100 mg/kg) was given intraperitoneally every 12 h for 3 days after antigen challenge. The number of coughs elicited by an aerosol of capsaicin (10(-4) M) was significantly (p < 0.01) decreased in carbocysteine groups (6.13 +/- 0.59 at 10 mg/kg, 4.88 +/- 0.67 at 30 mg/kg, and 4.50 +/- 0.33 at 100 mg/kg during 3 min measurement) compared with the control group (9.75 +/- 0.53). Furthermore, carbocysteine dose dependently repaired the antigen-induced decrease of NEP activity in the tracheal tissue, but it did not influence the bronchial hyperresponsiveness or bronchoalveolar lavage cell component. These findings suggest that carbocysteine promotes the repair of damaged epithelium by allergic reaction and may be useful in allergic airway diseases accompanied by isolated chronic coughing, especially eosinophilic bronchitis without asthma and tracheobronchitis with cough hypersensitivity.

Administration, Inhalation↗

PubMed2001

[Plasma (1-->3)-beta-D-glucan level in allergic bronchopulmonary aspergillosis].

We measured the plasma (1-->3)-beta-D-glucan (beta-DG) levels in patients with allergic bronchopulmonary aspergillosis (ABPA) and compared their temporal changes with those of serum IgE and eosinophil counts in the peripheral blood. The subjects were three ABPA patients who were newly diagnosed or had had a relapse between May 1998 and April 1999. Before treatment, all three cases showed high plasma beta-DG values, which declined following corticosteroid treatment with or without oral itraconazole. In two cases, the beta-DG values rose again on relapse. beta-DG values showed a tendency to change in parallel with IgE, although they moved in the opposite direction after a relapse in one case. The present findings suggest that the plasma beta-DG level may be a useful follow-up indicator of the infectious aspect of this disease.

Aged↗

PubMed2001

[A case of pneumonia, septic pulmonary embolisms with cavities, bilateral large lung abscesses, and multiple liver abscesses caused by Klebsiella pneumoniae].

A 64-year-old man suffering from diabetic hyperosmolar non-ketotic coma was admitted for acute lung abscess in the left apical lung field. Sputum culture and blood culture showed a heavy growth of Klebsiella pneumoniae (K. pneumoniae). He was suffering from sepsis, septic pulmonary embolisms with cavities, bilateral pulmonary consolidations, and multiple liver abscesses. Gradually, the bilateral lung consolidations resolved and areas of consolidation were noted to undergo extensive cavitation bilaterally. Cavitation and abscess formation are frequent complications of K. pneumoniae. Generally, large bilateral lung abscesses caused by K. pneumoniae have a poor prognosis. Cavity nodules are often present in septic pulmonary embolisms. We report a very rare case in a patient with three types of cavities with differing mechanisms. The first was an acute lung abscess, the second, septic pulmonary embolisms with cavities, and the third, large bilateral lung cavities noted in the course of resolving consolidations.

Bacteremia↗

PubMed2001

[A case of relapsing polychondritis monitored by daily peak flow measurement].

A 55-year-old man was admitted to our hospital with dyspnea and stridor. At presentation, he also had a low grade fever, arthralgia and nasal obstruction. His chest roentgenogram showed diffuse tracheal narrowing, and chest CT revealed a thickened tracheal wall and fractured cricoid and thyroid cartilages. A diagnosis of relapsing polychondritis was made on the basis of his symptoms and in accordance with Damiani's criteria and CT findings. Daily peak flow (PEF) monitoring was carried out to assess the disease condition of the trachea. Methylprednisolone pulse therapy was started, and was followed by oral prednisolone, which improved his condition immediately, but reduction of oral prednisolone led to recurrence. The clinical course was clearly evaluated by PEF monitoring, but the change was undetectable on chest CT. Dapson, cyclophosphamide, and inhaled steroid were administered with oral prednisolone and the patient's condition has since been fair and stable. PEF monitoring may be useful for the early detection of recurrence in cases of relapsing polychondritis.

Humans↗

PubMed2001

[Eosinophilic airway diseases presenting with isolated cough except for asthma].

Cough variant asthma (CVA), atopic cough (AC) and eosinophilic bronchitis without asthma (EB) are eosinophilic airway diseases presenting with isolated chronic cough. Among them, bronchodilators are effective only in CVA. Bronchial responsiveness, diurnal variation of pulmonary function and bronchomotor tone are mildly increased to intermediate levels between mild asthma and normal in CVA, but not in AC or EB. Cough sensitivity is heightened in atopic cough and probably in EB, but not in CVA. Bronchoalveolar lavage eosinophilia is present in CVA and EB, but absent in AC. As asthma onset has been recognized in nearly 30% patients with CVA, but not in AC, long-term inhaled corticosteroid therapy is recommended only in CVA.

Adrenergic beta-2 Receptor Agonists↗

PubMed2001

[A case report of advanced hepatocellular carcinoma successfully treated with surgical multi-ablation therapy based on radio-frequency thermal ablation].

We report a patient with advanced hepatocellular carcinoma (HCC) who was successfully treated with multi-ablation therapy by the surgical method of laparotomy and partial thoracotomy. A 67-year-old man, who had undergone transcatheter arterial embolization (TAE) three times for advanced HCC with hepatitis C, presented at our hospital in May 2001. Although TAE had been performed 3 times starting 2 years earlier, interventional therapy for recurrent tumors is difficult because of stenosis and obstruction of regional hepatic arteries. Computed tomography of the liver revealed five tumors in both lobes and the tumor in segment VIII presented difficulty for percutaneous ablation treatment due to its closeness to the trunk of the hepatic vein. Multi-ablation therapy consisting of radio-frequency ablation, microwave ablation and ethanol injection was selected for this patient. By laparotomy and partial thoracotomy, we performed multi-ablation therapy safely and accurately for each tumor. After this treatment, 5 tumors in both lobes showed no viability on dynamic CT and the patency of the right hepatic vein was preserved. Six months after the treatment, one remnant mass appeared in segment V. An additional two sessions of percutaneous RFA were performed for this tumor. At the end of these treatments, enhanced CT revealed no viability of the tumors, and serum alpha-fetoprotein and PIVKA-II level dropped to the normal range. This case suggests that multiple ablation therapy with a surgical method is feasible and useful in cases of advanced hepatocellular carcinoma.

Aged↗

PubMed2001

[A case of tuberous sclerosis with pulmonary lymphangiomyomatosis].

A 52-year-old woman complained of exertional dyspnea. She had two sons with tuberous sclerosis and presented with facial angiofibroma and bilateral renal angiomyolipomas. Her chest radiograph demonstrated diffuse reticular shadows and chest CT revealed numerous well-defined cysts outlined by thin walls. Pulmonary lymphangiomyomatosis was diagnosed by transbronchial biopsy that showed multifocal proliferation of immature smooth muscle cells located in the walls of some bronchi, and in alveolar walls and pulmonary vessels. Immunoreactivity for SMA and HMB 45 was present in the same cells, but immunostaining for estrogen and progesterone receptors was negative. Much is still unknown about pulmonary lymphangiomyomatosis and pulmonary involvement in tuberous sclerosis. Further studies, such as gene analysis, will clarify the relationship between these diseases.

Female↗

PubMed2000

The effect of the antipsychotic drug mosapramine on the expression of Fos protein in the rat brain: comparison with haloperidol, clozapine and risperidone.

In this study, we examined the effect of the acute p.o. administration of the antipsychotic drug mosapramine, as well as the antipsychotic drugs clozapine, haloperidol and risperidone, on the expression of Fos protein in the medial prefrontal cortex, nucleus accumbens and dorsolateral striatum of rat brain. The administration of mosapramine (1 or 3 mg/kg) significantly increased the number of Fos protein positive neurons in the medial prefrontal cortex, but not in the dorsolateral striatum. In addition, mosapramine (1, 3 or 10 mg/kg) produced a dose-dependent increase in the number of Fos protein positive neurons in the nucleus accumbens. The acute administration of 10 mg/kg of mosapramine significantly increased the number of Fos protein positive neurons in all brain regions. The acute administration of clozapine (30 mg/kg), similarly to mosapramine at lower doses (1 or 3 mg/kg), significantly increased the number of Fos protein positive neurons in the medial prefrontal cortex and nucleus accumbens, but not dorsolateral striatum. In contrast, haloperidol (0.3 mg/kg) significantly increased the number of Fos protein positive neurons in the nucleus accumbens and dorsolateral striatum, but not medial prefrontal cortex. The acute administration of risperidone (0.3 or 1 mg/kg) did not affect the number of Fos protein positive neurons in the medial prefrontal cortex, nucleus accumbens or dorsolateral striatum of rat brain, whereas a 3 mg/kg dose of risperidone significantly increased the number of Fos protein positive neurons in all brain regions. These results suggest that the ability of mosapramine to enhance expression of Fos protein in the medial prefrontal cortex may contribute to a clozapine-like profile with respect to actions on negative symptoms in schizophrenia. Furthermore, the lack of effect of low doses of mosapramine on Fos protein expression in the dorsolateral striatum, an area believed to play a role in movement, suggests that it may have a lower tendency to induce neurological side effects.

Animals↗

PubMed2000

Effect of hypotension severity on hippocampal CA1 neurons in a rat global ischemia model.

Neuronal death in the hippocampal CA1 subregion has been shown to occur in a delayed manner after transient global ischemia. The 2-vessel occlusion model is one of the most frequently used global ischemia paradigms in rodents. Although researchers often fail to induce bilateral delayed CA1 neuronal death, the importance of hypotension severity has not been fully discussed. We induced 10 min of global ischemia with 2-vessel occlusion and various severities of hypotension in rats, and the subsequent neuronal damage and neurogenesis in the hippocampal CA1 pyramidal cell layer were immunohistochemically studied. Neuronal apoptosis after global ischemia was also characterized by terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphate-biotin nick end labeling (TUNEL). The mean arterial blood pressure of 31-35 mmHg was the most appropriate range of hypotension in this model because of low mortality and consistent bilateral CA1 injury. Most of the neurons in the CA1 pyramidal cell layer lost neuron specific nuclear protein and became TUNEL-positive 3 days after ischemia. There was no evidence of apoptosis or neurogenesis at 7-28 days. There were ischemia-tolerant neurons in the CA1 pyramidal cell layer that survived delayed neurodegeneration, however, further studies are necessary to characterize the property of these neurons.

Animals↗

PubMed2000

Endoscopic surgery for lateral cervical cysts. A report of three cases.

Recently, endoscopic surgery has been applied to cervical exploration. We have developed new techniques for endoscopic neck surgery, and in this paper report our experience with three patients with lateral cervical cysts. A 5- or 10-mm midline trocar for the endoscope and two 5- or 10-mm lateral trocars were inserted from the anterior chest wall and/or both axillary fossae to avoid neck scars. There were no intraoperative complications. Slight subcutaneus emphysema was present postoperatively, but it was limited to the neck and disappeared in a few days. The incisions were completely covered by the patients' undergarments. This is the first report of endoscopic lateral cervical cystectomy.

Adolescent↗

PubMed2000

Reduction of the DNA base excision repair protein, XRCC1, may contribute to DNA fragmentation after cold injury-induced brain trauma in mice.

The X-ray repair cross-complementing group 1 (XRCC1) protein plays a central role in the DNA base excision repair pathway by interacting with DNA ligase III and DNA polymerase beta. The present study examined the protein expression of XRCC1 and DNA fragmentation before and after cold injury-induced brain trauma (CIBT) in mice, in which apoptosis is assumed to participate. Immunohistochemistry showed the nuclear expression of XRCC1 in the entire region of the control brains. Fifteen minutes after CIBT, nuclear immunoreactivity was predominantly decreased in the inner boundary of the lesion, followed by a significant reduction of XRCC1 in the entire lesion 4 h after CIBT. A characteristic 70-kDa band was detected in the non-traumatic area, and was markedly decreased after CIBT as shown by Western blot analysis. DNA fragmentation was also observed after CIBT, and double staining with XRCC1 immunohistochemistry and terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphate-biotin nick end labeling showed a spatial relationship between XRCC1 loss and DNA fragmentation 24 h after CIBT. These data indicate that early decrease of XRCC1 and failure of the DNA repair mechanism may contribute to DNA-damaged neuronal cell death after CIBT.

Animals↗

PubMed2000

Effects of antipsychotic drugs on neurotoxicity, expression of fos-like protein and c-fos mRNA in the retrosplenial cortex after administration of dizocilpine.

In this study, we examined the effect of clozapine, olanzapine, risperidone and haloperidol on the neuropathology (i.e. neuronal vacuolization) and the expression of Fos-like protein and c-fos mRNA in the retrosplenial cortex of female Sprague-Dawley rats induced by the NMDA receptor antagonist dizocilpine. Pretreatment (15 min) with clozapine or olanzapine, but not risperidone or haloperidol, blocked the neuronal vacuolization produced by dizocilpine (0.5 mg/kg, s.c.) in the rat retrosplenial cortex in a dose-dependent manner. Furthermore, pretreatment (15 min) with clozapine or olanzapine, but not risperidone or haloperidol, significantly attenuated the expression of Fos-like protein in the retrosplenial cortex induced by dizocilpine (0.5 mg/kg, s.c.) in a dose-dependent manner. The marked expression of c-fos mRNA in the rat retrosplenial cortex induced by the administration of dizocilpine (0.5 mg/kg, s.c.) was significantly attenuated by pretreatment (15 min) with clozapine (10 mg/kg) or olanzapine (10 mg/kg), but not risperidone (10 mg/kg) or haloperidol (10 mg/kg). The present results suggest that pharmacologically relevant doses of clozapine or olanzapine, but not risperidone or haloperidol, block the neuropathological changes and the expression of Fos-like protein and c-fos mRNA in the rat retrosplenial cortex elicited by the administration of dizocilpine. It is possible that the blockade of dizocilpine-induced neuropathological changes by clozapine and olanzapine may be related to the unique antipsychotic actions of these drugs in schizophrenic patients, although this remains to be verified.

Animals↗

PubMed2000

The cytosolic antioxidant copper/zinc-superoxide dismutase prevents the early release of mitochondrial cytochrome c in ischemic brain after transient focal cerebral ischemia in mice.

Release of mitochondrial cytochrome c into the cytosol is a critical step in apoptosis. We have reported that early release of cytochrome c in vivo occurs after permanent focal cerebral ischemia (FCI) and is mediated by the mitochondrial antioxidant manganese superoxide dismutase (SOD). However, the role of reactive oxygen species produced after ischemia-reperfusion in the mitochondrial apoptosis process is still unknown, although overexpression of copper/zinc-SOD (SOD1), a cytosolic isoenzyme, protects against ischemia-reperfusion. We now hypothesize that the overexpression of SOD1 also prevents apoptosis after FCI. To address this issue, we examined the subcellular distribution of the cytochrome c protein in both wild-type mice and in SOD1 transgenic (Tg) mice after transient FCI. Cytosolic cytochrome c was detected as early as 2 hr after reperfusion, and correspondingly, mitochondrial cytochrome c was significantly reduced after FCI. Cytosolic cytochrome c was significantly lower in the SOD1 Tg mice compared with wild types 2 (p < 0.0001) and 4 (p < 0.05) hr after FCI. Apaf-1, which interacts with cytochrome c and activates caspases, was constitutively expressed in both groups of animals, with no alteration after FCI. Double staining with cytochrome c immunohistochemistry and terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphate-biotin nick end labeling showed a spatial relationship between cytosolic cytochrome c expression and DNA fragmentation. A significant amount of DNA laddering was detected 24 hr after ischemia and was reduced in SOD1 Tg mice. These data suggest that SOD1 blocks cytosolic release of cytochrome c and could thereby reduce apoptosis after transient FCI.

Animals↗

PubMed2000

[Laparoscopic radical nephrectomy for renal cell carcinomas; report on two initial cases].

We recently performed a laparoscopic radical nephrectomy (LRN) on two patients with a renal cell carcinoma. Case 1, a 72-year-old man, was diagnosed as having a renal cell carcinoma 2.5 cm in diameter in the right kidney, and also a submucosal tumor of the cecum. LRN and laparoscopically assisted ileocecal resection were performed using a transperitoneal approach on September 28, 1999. Total operation time and blood loss during the operation were 308 minutes and 320 ml, respectively. The operation time needed for LRN, which was calculated as the total operation time minus the time spent on ileocecal resection, was 199 minutes. There were no complications after surgery, and the patient was recommended for discharge on the 7th postoperative day, but was actually discharged on the 10th postoperative day. Case 2, an 81-year-old man, was diagnosed as having a renal cell carcinoma 3.0 cm in diameter in the right kidney. He had been undergone a total gastrectomy for a gastric carcinoma at age 77, and a sigmoidectomy for a sigmoid colon carcinoma at age 79. A transperitoneal approach was applied for LRN to detect any recurrence of previous carcinomas on September 30, 1999. During adhesiolytic procedures, the colon was injured due to an inappropriate maneuver of the grasping forceps. A small laparotomy (5 cm) was required for repair of the colon. The total operation time and blood loss during surgery were 370 minutes and 850 ml. The operation time calculated from the video of LRN was 274 minutes. Two additional surgical procedures were required in this case. The first was for a postoperative intraperitoneal hemorrhage due to the hemoclip dropping out of the small vein. The second was for hemorrhage in the abdominal wall. Fortunately, the clinical course after surgery was good and the patient was discharged on the 8th postoperative day. There were no complications in case 1. Omitting ileocecal resection was considered to speed up oral intake, leading to earlier discharge. However, major complications occurred in case 2. It is important to clarify the cause of postoperative hemorrhage by careful observation of the video recording, in order to suggest safer procedures in laparoscopic surgery. Although these are only two LRN experiences, we are convinced that LRN can improve postoperative QOL (Quality of life) and is an acceptable alternative for the treatment of renal cell carcinomas.

Aged↗

PubMed2000

[The C tube in biliary surgery--its development and clinical application].

BACKGROUND: The T tube procedure for bile drainage after biliary surgery has been used all over the world for more than 90 years. However, this method has serious drawbacks: a high complication ratio and a need for long-term hospitalization. Therefore other bile drainage methods including PTGBD, PTBD and ENBD have been developed, but none has so far been able to replace T tube. We have developed a new technique for bile drainage using the C tube (cystic duct tube), which is a slender tube (6Fr. polyvinyl) inserted via the cystic duct into the common bile duct (CBD). We have used C tube in more than 400 cases over the last 20 years: for open surgery during the first 10 years, and for laparoscopic surgery in the last 10 years. Here we describe the history of improvements in the C tube method and the techniques of C tube application in biliary surgery. Elastic surgical suture has been used to fix the C tube to the cystic duct, which successfully prevented bile leakage from the ductal stump after withdrawal of the tube. C tube is not only used for postoperative bile drainage but also for the management of remnant stones. The purpose of this study is to assess the safety and benefits of the C tube procedure. METHODS: I: From 1980 to 1998, 335 cholecystectomized cases which had undergone the C tube procedure were examined for complications resulting from C tube placement. II: We analyzed 134 patients with choledocholithiasis: 34 patients had been treated using C tube drainage, and 100 patients had been treated with the T tube procedure after undergoing CBD exploration. The main outcome criteria were: the frequency of post-operative complications, quantity of bile drainage, drainage period, and length of post-operative hospital stay. III: Between 1990 and 1999, 131 patients (15.2%) of a total of 860 laparoscopically cholecystectomized patients with gallstones underwent C tube treatment. We assessed the usefulness of the C tube procedure for the detection and management of remnant stones. RESULTS: I: There were no major complications (bile-leakage, CBD stenosis, etc.) in 335 cases which underwent the C tube procedure. Minor complications related to C tube were: spontaneous withdrawal of the tube in 5 cases, movement of the tube tip in 17 cases, and difficulties during tube removal in 32 cases which included slight resistance. Two cases had liver dysfunction (GOT 705 IU/l and 488 IU/l), although this was easily normalized after withdrawal of the tube tip from the duodenal papillae into the CBD. II: The frequency of complications in patients who underwent the C tube procedure was zero, whilst in the T tube group the major complication rate was 3% and the minor complication rate was 21%. The quantity of bile drainage was 283.6 +/- 22.9 ml/day in the C tube group compared with 302.7 +/- 10.3 ml/day in the T tube group, showing no significant difference. The drainage period (5.9 +/- 0.6 days) in the C tube group was significantly shorter than in the T tube group (27.7 +/- 0.9 days). Hospital stays (11.6 +/- 0.6 days) in the C tube group were significantly shorter than in the T tube group (45.0 +/- 1.5 days). III: Remnant CBD stones were detected by postoperative cholangiography via the C tube in 28 (21.4%) of the C tube replacement cases and in 3.3% of all the laparoscopically cholecystectomized patients. Seventeen patients with remnant stones were managed using glyceryl trinitrate CBD perfusion-induced relaxation of the sphincter of Oddi. The remaining patients were managed with endoscopic papillary balloon dilatation (EPBD) and/or endoscopic sphincterotomy (EST) without reoperation. We also have described other applications of the C tube procedure for the evaluation of sphincter of Oddi motility as an indication for EST, for bile drainage in liver resection, in the treatment of liver injuries, and for duodenal decompression after duodenal surgery. Finally we have mentioned the possibility of C tube application in the management of obstructive jaundice and bile drainage in liver transplantation surgery. CONCLUSION: The C tube method in biliary surgery is safe and useful in comparison with the T tube method. We are strongly convinced that the T tube will be completely replaced by the C tube.

Aged↗

PubMed2000

Subarachnoid hemolysate produces DNA fragmentation in a pattern similar to apoptosis in mouse brain.

Stroke and traumatic brain/spinal cord injuries are often associated with hemorrhage. Despite the relative frequency of hemorrhage in the central nervous system (CNS), little is known about what role blood and hemoglobin (Hb) play in mediating cellular injury. Since Hb and hemolysate have been associated with generation of oxidative stress and cell injury, we examined whether apoptosis was present after cortical exposure to subarachnoid hemolysate. Subarachnoid hemorrhage (SAH) was induced in CD-1 mice (n=25) by injection of 50 microl of autologous hemolysate over the right parietal cortex. Saline-injected mice (n=13) were used as controls. Subjects were sacrificed at 24 h. Transcardiac perfusion fixation was performed on a subgroup of hemolysate- (n=15) and saline-injected (n=9) animals. Sections were stained for DNA fragmentation using the terminal deoxyuridine nick end-labeling (TUNEL) method and also immunostained for the hemeoxygenase-1 (HO-1) protein to assess blood distribution. In the remaining animals (n=6 SAH, n=4 saline), DNA was extracted and precipitated from 40 mg of tissue and subjected to electrophoresis on a 1.5% agarose gel. DNA fragmentation was evident on TUNEL staining in 10/15 subjects injected with hemolysate as compared to 0/9 subjects injected with saline (p<0.01, Fisher exact test). TUNEL-positive cells were most abundant closest to the site of cortical SAH, as evidenced by HO-1 immunoreactivity. TUNEL-positive cells were also seen remotely in the hippocampus and basal forebrain. The presence of apoptosis was suggested by DNA laddering on electrophoresis in the hemolysate-injected subjects (4/6 animals). No laddering was evident in saline-injected subjects (n=4). These results provide evidence that the presence of subarachnoid blood products is associated with DNA fragmentation and apoptotic cell death.

Animals↗

PubMed2000

Dizocilpine-induced neuropathological changes in rat retrosplenial cortex are reversed by subsequent clozapine treatment.

In this study, we examined the effect of post-treatment with clozapine on the neuropathological changes in the rat retrosplenial cortex induced by the administration of non-competitive NMDA receptor antagonist dizocilpine ((+)-MK-801). The maximal increase in vacuolized neurons, which are representative of neuropathology, was observed 4 hours after a single injection of dizocilpine (0.5 mg/kg s.c.), with a complete reversal of the neuropathology after 16-24 hours. The administration of clozapine (10 mg/kg, i.p.,) 4 hours after the administration of dizocilpine significantly decreased the number of vacuolized neurons in the retrosplenial cortex 6, 8 or 10 hours after administration of dizocilpine, compared to vehicle-treated animals. Furthermore, the administration of clozapine (5, 10 or 20 mg/kg i.p.) 4 hours after the administration of dizocilpine produced a significant decrease in the number of vacuolized neurons in the retrosplenial cortex in a dose-dependent manner when measure 6 hours post-dizocilpine. These results show that neuropathological changes in the rat retrosplenial cortex produced by dizocilpine can be attenuated by post-treatment with clozapine.

Animals↗

PubMed2000

Neoadjuvant intraarterial infusion chemotherapy in patients with stage IB2-IIIB cervical cancer.

OBJECTIVES: The purpose of this study was determine the effect of neoadjuvant intraarterial chemotherapy (NAIC) on the prognosis of patients with locally advanced cervical cancer. METHODS: From January 1992 to December 1997, 26 previously untreated patients with stage IB2-IIIB cervical cancer were enrolled in the study. NAIC was administered for more than two courses every 3 weeks using a combination of 17.5 mg/m(2) bleomycin, 7 mg/m(2) mitomycin-C, and 75 mg/m(2) cisplatin via the bilateral internal iliac artery. Pathologic findings were evaluated with histologic examinations of surgical specimens. A nonrandomized control group of 120 patients who underwent conventional treatment between 1980 and 1991 was used for comparison. RESULTS: Nineteen (73.1%) of the 26 patients responded to initial chemotherapy, permitting a radical hysterectomy with pelvic lymphadenectomy in 14 patients. The remaining 5 patients received radiotherapy. One of 7 nonresponders was able to undergo radical surgery. Pathologic complete responses were found in 4 of the 15 patients who underwent radical surgery. The incidence of lymph node metastasis, parametrial infiltration, and vascular space involvement in the 15 patients who received NAIC followed by radical surgery was significantly lower than that in the control group (13.3, 6.7, and 13.3% vs 54.2, 43.8, and 60.4%). The overall 5-year estimated survival rate was significantly higher for all 26 patients who received NAIC (80.0%) than for the control group (59.6%). In stage II and III, the 5-year survival rate for patients who received NAIC was significantly higher than that in the control group (83.3 and 77.8% vs 68.1 and 49.8%). CONCLUSIONS: These preliminary results suggest that NAIC is able to eliminate effectively the pathologic risk factors in the pelvic cavity, to improve the operability in patients with stage IIIB cervical cancer, considered inoperable, and to improve the prognosis of patients with locally advanced cervical cancer.

Adenocarcinoma↗