Quantitative evaluation of brainstem involvement in multiple system atrophy by diffusion-weighted MR imaging

Abstract. In multiple system atrophy (MSA), symptoms associated with dysfunctions of the brainstem and autonomic nervous system are important prognostic factors. We investigated brainstem involvement in 12 patients with MSA with predominant cerebellar symptoms (MSA-C) (mean age, 56.3 ± 9.9 years, median disease duration, 3 years), and 11 controls (57.6 ± 12.0 years) matched for age using diffusion-weighted MR imaging (DWI). We demonstrated that apparent diffusion coefficients (ADCs) in the pons and middle cerebellar peduncle of MSA-C patients are significantly higher than those of normal controls even though the patients are in the early stage of the disease. Furthermore, we demonstrated that increased ADC values correlated well with the disease duration. The current study demonstrated that DWI is a useful noninvasive method for the quantitative evaluation of the brainstem involvement in MSA-C patients.     

Dimension of Typus melancholicus on Kasahara's Inventory for the Melancholic Type Personality

BACKGROUND: Traditionally, Typus melancholicus (TM) was considered, a priori, to represent unidimensionality. Recent studies have suggested that TM is not a personality trait, but rather a constellation of personality traits. The purpose of this study was to examine whether TM on Kasahara's Inventory for the Melancholic Type Personality (KIMTP), considered to represent one of the valid TM questionnaires, is comprised of personality dimensions, and if so, which dimension is essential for distinguishing depressive subjects from control subjects. SUBJECTS AND METHODS: To clarify the dimensionality of TM scores on KIMTP, factor analysis of the TM scores was conducted using principal factor analysis followed by varimax rotation. Comparisons were then made between endogenous depressive patients (n = 38), nonendogenous depressive patients (n = 20), and healthy volunteers (n = 81) for total KIMTP score and factor scores using analysis of covariance, adjusting for sex and age. RESULTS: Factor analysis of KIMTP revealed 2 distinct clusters of items, i.e. 'harmony in personal relationships' (factor 1) and 'social norms' (factor 2). Endogenous and nonendogenous depressive patients showed significantly higher KIMTP total and factor 1 scores than did control subjects. However, no significant differences were observed for KIMTP total score and scores of individual factors between endogenous and nonendogenous depressive patients. CONCLUSIONS: The present results indicate that TM on KIMTP represents a constellation of personality traits, and that the factor 'harmony in personal relationship' possesses the essential meaning for assessing TM.     

Laparoscopically assisted total gastrectomy with sentinel node biopsy for early gastric cancer: preliminary results

This study sought to describe a procedure involving laparoscopically assisted total gastrectomy (LATG) with sentinel node biopsy (SNB) and to evaluate the results of the first three patients. LATG for early gastric cancer was performed with sentinel node (SN) identification using a combined patent blue-violet dye and 99mtechnetium-labeled tin colloid technique. Laparoscopically resected SNs were processed for frozen section examination by routine hematoxylin and eosin (H&E) and immunohistochemical cytokeratin (IHC-CK) stains. LATG consists of a four-surgical port technique, removal of the specimen through a small 5-cm laparotomy, and stapled Roux-en-Y esophagojejunostomy. Five patients were candidates for LATG with SNB between March 2001 and June 2003; two had open surgery because of a tumor extending the serosal surface and peritoneal dissemination, whereas in the remaining three, SNs were successfully identified and evaluated with no evidence of sentinel node (micro) metastases intraoperatively. Based on the results of SNB, three patients underwent LATG with adequate lymphadenectomy. Mean operative time and blood loss were 375 min and 219 mL, respectively. No dissected lymph nodes had evidence of metastasis by H&E and IHC-CK on permanent sections. LATG with SNB followed by adequate lymphadenectomy is technically feasible, and with its acceptable operative time and blood loss, presents an excellent therapeutic option for early gastric cancer; while SNB and subsequent frozen section analysis by H&E and IHC-CK staining is a rapid and reliable diagnostic method for intraoperative detection of SN (micro) metastasis. This combination treatment is a promising alternative to laparoscopic gastrectomy with conventional lymphadenectomy.     

Clinical study of modified M-VAC therapy with one 21-day cycle for advanced urothelial cancer

Although M-VAC therapy is a standard chemotherapy for advanced transitional cell carcinoma, the treatment schedule has to be delayed or cancelled in many patients because of the toxicity. To reduce the toxicity we modified the treatment schedule of M-VAC treatment. The dosages of this simplified M-VAC therapy were 30 mg/m2 methotrexate (on day 1), 3 mg/m2 vinblastine (on day 2), 30 mg/m2 doxorubicin (on day 2) and 70 mg/m2 cisplatin (on day 2), with courses repeated every 21 days for four cycles as a principle. Seventeen patients with histologically proven advanced transitional cell carcinoma were treated with this simplified M-VAC therapy without dose modification or delay. The median number of cycles was 4. Neutropenia, anemia and thrombopenia (grade 4) was observed in 2, 1 and 2 patients respectively, but no drug-related deaths were observed. Complete response and partial response were achieved in 2 (12%) and 10 (59%) patients respectively. Of 2 complete responders one patient was alive without evidence of disease at 12 months and another patient died of the disease at 42 months. Of 10 partial responders 6 patients underwent the additional surgical resection of residual tumors. Of these 6 patients 3 patients are alive without evidence of disease at 6, 30 and 31 months. The remaining 3 developed recurrence and 2 died of the disease at 13 and 29 months. Five non-responders died of the disease at 5 months after the start of the therapy. Response rate of simplified M-VAC therapy was excellent and treatment duration was short. However, relapses were commonly observed as well as the original M-VAC treatment.     

The effects of Na+ -H+ exchange inhibitor, KB-R9032, administered at the time of reperfusion in perfused rat heart

BACKGROUND: We have reported that pretreatment with KB-R9032, a newly developed Na+ -H+ exchange inhibitor is protective against reperfusion-induced ventricular arrhythmia in the isolated perfused rat heart. This study was conducted to elucidate whether the drug is equally effective when it is given at the time of reperfusion. METHODS: Male Wistar rat hearts (n=32, 16 for each group) were perfused by means of Langendorff technique. Each heart was subjected to regional ischemia (occlusion of the left anterior descending coronary artery for 11 minutes) and to three minutes of reperfusion (release of the occlusion). KB-R9032 4 mg (one shot group) or a vehicle without drug (control) were given 30 seconds before the reperfusion to 30 seconds after the reperfusion. RESULTS: In the control group reperfusion-induced ventricular fibrillation (VF) occurred in 91.7% and the duration was 165 +/- 14.4 seconds, but, in one shot group, the incidence of VF decreased to 6.3% and the duration of VF was reduced to 0.4 +/- 0.4 seconds, respectively (P<0.05 vs control group). CONCLUSIONS: It has been shown in this study that the Na+/H+ exchange inhibitor KB-R9032 given at the time of reperfusion suppresses reperfusion arrhythmias in the ischemia-reperfusion model of isolated rat heart.     

Monitoring and preventing blood flow insufficiency due to clip rotation after the treatment of internal carotid artery aneurysms

The authors report a case in which anterior choroidal artery (AChA) blood flow insufficiency due to aneurysm clip rotation was detected intraoperatively by motor evoked potential (MEP) monitoring and ischemia was successfully avoided. The patient had an incidentally discovered aneurysm for which occlusion of its neck was performed through a standard frontotemporal craniotomy without changing the MEP amplitude. After it was confirmed that the surrounding arteries were not stenotic, the brain retractor on the frontal lobe was released; MEP amplitude subsequently decreased. Rotation of the clip toward the frontal base by repositioning of the frontal lobe caused the AChA stenosis at the origin of its branches. On reorienting the clip toward the frontal lobe, the AChA stenosis was released and MEP amplitude recovered. To prevent repeated clip rotation, a large amount of gelatin (Spongel) was inserted between the frontal base and the clip. The authors confirmed that clip rotation did not occur after repositioning of the frontal lobe. Motor evoked potential amplitude was maintained until dural closure. Postoperatively, the patient demonstrated no neurological deficit and there was no newly developed low-density area on computerized tomography scans.     

Infectivity enhanced, cyclooxygenase-2 promoter-based conditionally replicative adenovirus for pancreatic cancer

BACKGROUND AND AIMS: Pancreatic cancer is one of the most aggressive human malignancies. Conditionally replicative adenoviruses (CRAds) have shown some promise in the treatment of cancers. However, to date, their application for pancreatic cancer has met several obstacles: one is lack of a good control element to regulate replication, and the other is relatively low adenoviral infectivity. Thus, we constructed infectivity enhanced cyclooxygenase (COX)-2 promoter-based CRAds to develop a safe and effective therapeutic modality. METHODS: The CRAds were designed to achieve COX-2 promoter-controlled E1 expression for regulated replication (COX-2 CRAds). The infectivity-enhanced CRAds also have an RGD-4C motif in the adenoviral fiber-knob region. The selectivity and efficacy of these constructs were analyzed with cell lines in vitro. The in vivo therapeutic effect and viral replication were analyzed with a xenograft model. Pathology of the major organs and E1 RNA levels in the liver were also studied after systemic administration. RESULTS: The COX-2 CRAds showed a selective cytocidal effect in vitro in COX-2-positive cells and killed most of the pancreatic cancer cells. In vivo, intratumoral administration of the infectivity-enhanced COX-2 CRAds (10(9) particles) showed a strong antitumor effect comparable to wild-type virus, whereas the COX-2 CRAds without infectivity enhancement showed a limited effect. Viral replication was confirmed in the xenograft tumors. Systemic administration did not cause any detectable toxicity; the E1 RNA level in the liver after COX-2 CRAd administration was minimal. CONCLUSIONS: Infectivity-enhanced COX-2 CRAd is a promising agent for the treatment of pancreatic cancer.     

A case report of disseminated malignant mesothelioma of peritoneum responding remarkably to thalidomide, celecoxib, vinorelbine and CDDP

Malignant mesothelioma (MM) is a rare neoplasm that is commonly fatal within 12-17 months after diagnosis. There are no widely accepted curative approaches. It recurs even after the most aggressive surgical resection. MM is resistant to chemotherapy and radiation. Most of the chemotherapeutics have been evaluated in MM, however, no drugs have a response rate greater than 20%. The combination of drugs has no increased efficacy compared with single agents. Vinorelbine has useful clinical activity against MM with a response rate of 24%. Vascular endothelial growth factor (VEGF) is expressed in MM and pleural effusion of MM. There is a significant inverse correlation between serum VEGF levels and MM patient survival. Cyclooxygenase-2 (COX-2) is expressed in MM. COX-2 plays an important role in tumor growth, invasion, and angiogenesis. VEGF and COX-2 are potential targets in MM. The downregulation of bFGF, VEGF, and maybe some other angiogenesis stimulators, is one of the antiangiogenic mechanisms of thalidomide. Celecoxib is a potent selective COX-2 inhibitor. Here we report a case of disseminated malignant mesothelioma of peritoneum responding remarkably to thalidomide, celecoxib, vinorelbine and CDDP.