Changes in folate concentration in Yoshida sarcoma after administration of leucovorin or cisplatin

Both leucovorin (LV) and cisplatin ( cis-dichlorodiammine platinum II, CDDP) act as modulators of 5-fluorouracil (5-FUra) by increasing the intracellular concentration of reduced folate. We measured intracellular folate levels following the administration of LV or cisplatin in tumor-bearing rats to determine the optimal schedules for their use as 5-FUra modulators. Donryu rats were inoculated with Yoshida sarcoma cells on the right flank. Seven days after tumor inoculation, the animals were injected with LV or CDDP. The kinetic and dose-related changes in intracellular folate concentration were analyzed by means of a binding assay. Folate levels in the tumor tissues were significantly higher than baseline 1 and 2 h after administration of LV and remained significantly high until 8 h after administration. Folate levels in the tumor tissues were significantly higher than baseline 1 and 2 h after cisplatin administration, then decreased to a rather low level 8 h after, and to a significantly lower level than baseline 24 h after administration. The folate levels in the tumor tissue increased in proportion to the dose of LV, but did not increase when the dose of cisplatin was increased from 1 mg/kg to 8 mg/kg. Repeat high-dose administration of LV and repeat low-dose administration of cisplatin are advocated when they are used as modulators of 5-FUra.     

Reconstruction of right ventricular outflow tract with stentless xenografts in Ross procedure

To investigate whether the use of a stentless porcine aortic xenograft can be an alternative for right ventricular outflow tract (RVOT) reconstruction during the Ross procedure, 9 patients underwent the Ross procedure and RVOT reconstruction with a stentless xenograft since January 2000. After the aortic valve was replaced with a pulmonary autograft, a stentless xenograft with a xeno- pericardial roll was implanted in the RVOT. One patient required subsequent aortic valve replacement because of severe regurgitation of the pulmonary autograft. All patients recovered well from the operation. The right ventricle-pulmonary arterial pressure gradient was 18 +/- 7 mm Hg at discharge and was not significantly increased during the 2-year follow-up period. Although 1 patient died of ventricular arrhythmia 5 months after, his cardiac function was normal, and transpulmonary valve pressure was 19 mm Hg in the follow-up. The other 7 patients are currently in New York Heart Association functional Class I. Although long-term follow-up is required to explain the durability, the stentless xenograft with a pericardial roll is considered to be an alternative for reconstruction of the RVOT within 2 years after the Ross procedure.     

A 7-year follow-up study of cases with dementia to identify predictors of mortality

OBJECTIVES: To identify factors associated with mortality in cases with Alzheimer's disease (AD) and vascular dementia (VD), we conducted a seven-year follow-up study. METHODS: Subjects were recruited through three agents in Yamanashi prefecture. A total of 145 patients (56 men, 89 women, age at baseline 77 +/- 7.9, 80 +/- 8.5 years respectively) with AD and VD participated in the follow-up study. We analyzed the relationship between demographic or clinical variables and their survival using a Cox regression model. RESULTS: The analysis revealed that increased age, male gender, the degree of global function and past history of a fall/fracture were associated with a decreased survival rate. The rate was worse for patients with VD than for those with AD. After adjusting for age and gender, the mortality risk ratio was 1.7 (95% confidence interval 1.1-2.6) for the presence of a fall/fracture. The same analysis confined to 64 subjects for whom ApoE genotyping data were available replicated the results; a fall/fracture was a predictor of a worse survival rate. In addition, those with ApoE4 tended to have better survival rate than those without (P < 0.1). CONCLUSION: Those who are engaged in care for AD patients should appreciate the importance of a fall/fracture as a predictor of survival.     

In vivo immunogenicity of osteosarcoma cells that express B7-1a,an alternatively spliced form of B7-1

BACKGROUND: B7 family members play a central costimulatory role in T cell activation. We have previously identified B7-1a, an alternatively spliced form of B7-1. The function of B7-1a in induction of anti-tumor immunity remains uncertain. MATERIALS AND METHODS: The cDNAs of murine B7-1, B7-1a and B7-2 were introduced into a murine osteosarcoma cell line, LM8. The ability of B7 transfectants to elicit in vivo anti-tumor immunity was comparatively analyzed with respect to tumorigenecity, pulmonary metastasis and survival time. RESULTS: LM8 cells expressing B7-1, B7-1a, or B7-2 all elicited immunological responses in immunocompetent C3H/He mice. Notably, the anti-tumor effects were most obvious in mice inoculated with B7-1a-transfected LM8 cells. Such a difference among B7-transfectants became indistinguishable in immunodeficient nude mice. CONCLUSION: These findings indicate that B7-1a serves as a more efficacious costimulatory molecule than B7-1 or B7-2 in the induction and maintenance of anti-tumor immune responses against a poorly immunogenic osteosarcoma cell line.     

A case of large-cell lung cancer with liver metastasis successfully treated using combination chemotherapy with CDDP and vinorelbine

A 38-year-old woman presented to our hospital with the chief complaint of dyspnea. A chest radiograph showed pleural effusion of the right lung and a CT scan revealed liver metastasis. A tumor biopsy done under bronchoscopy revealed large-cell carcinoma of the lungs. She was given 4 courses of a combination therapy consisting of CDDP (80 mg/m2) and vinorelbine (25 mg/m2). The primary tumor in the right lung and liver metastasis were markedly reduced in size and a partial response was obtained. The combination therapy of CDDP and vinorelbine may become a standard chemotherapy for advanced non-small cell lung cancer.     

Pseudoxanthoma elasticum (PXE)-like calcification in adult dermatomyositis

A case of pseudoxanthoma elasticum (PXE)-like calcification in adult dermatomyositis (DM) is described. The patient was a 38-year-old woman with a history of dermatomyositis for 3 months. Yellowish, hard, papulo-plaque lesions, which looked like those of pseudoxanthoma elasticum, were noted on her left axilla. Calcium deposition was confirmed by X-ray, histopathological, and electron microscopic examinations. Histopathological and histochemical examinations showed acicular calcium deposition in the middle and deep dermis surrounded by mucin. Electron microscopic examination revealed that the calcium deposition was not on collagen fibers. These morphological features were distinct from those of PXE. We proposed the possibility that degenerated mucin or degenerated elastic fiber might result in subsequent calcium deposition in reticular calcinosis in adult DM. The calcification clinically disappeared without any specific treatment except for prednisolone and cyclophosphamide.     

Appearance of rectal varices in extrahepatic portal obstruction after treatment for esophago-gastric varices: a case report

We report a case of rectal varices that developed after endoscopic injection sclerotherapy (EIS) and Hassab's operation for esophageal varices with extrahepatic portal obstruction. A 54-year-old woman was admitted to our hospital in September 1997 for treatment of hematochezia. Emergent colonoscopy revealed tortuous rectal varices with a white plug. Angiography revealed that rectal varices were provided with backward blood flow by the inferior mesenteric vein due to extrahepatic portal obstruction. In this case, previous treatment, EIS and Hassab's operation, for esophago-gastric varices might have inhibited the development of collaterals apart from surface of gastrointestinal tract, such as para-esophageal collateral veins or spleno-renal shunt. Since the thrombus in the extrahepatic portal vein causes strong pressure on inferior mesenteric vein which is connected to the inferior vena cava via the inferior rectal vein, rectal varices might be developed. In this case, it was considered that rectal varices were not treated enough by endoscopic therapy because of regurgitant hyper blood flow against portal venous pressure. Therefore, rectal transection was performed. After the treatment, the patient suffered no further episodes of bleeding from rectal varices.     

The Effect of Immunosuppression on Aortic Dilatation in a Rat Aneurysm Model

This study was conducted to investigate whether systemic immunosuppression attenuated aortic dilatation in a rat aneurysm model. Sprague-Dawley rats were subjected to elastase infusion of the infrarenal aorta and divided into two groups of 12 rats each. The immunosuppression group (group 1) was given subcutaneous injections of cyclosporine A (5 mg/kg per day), azathioprine (2 mg/kg per day), and methylprednisolone (2 mg/kg per day) from the operative day until postoperative day (POD) 6. An additional subcutaneus injection of cyclophosphamide 30 mg/kg was also given on the operative day. The control group (group 2) was given subcutaneous injections of saline. Relaparotomy was performed on POD 7. After measurement of the aortic diameter, aortography and ultrasonography were performed in three rats from each group, following which the aortas were excised for histologic examination. The aortic diameter was significantly smaller in group 1 (2.58 ± 0.37 mm) than in group 2 (6.21 ± 1.74 mm) (P < 0.01) and the aortic lumen was slightly dilated in group 1, whereas it was spherically dilated in group 2. Total loss of elastic tissue was seen in both groups. Inflammatory cell infiltration and collagen fiber fragmentation were noted in group 2, whereas very little inflammatory cell infiltration and well-preserved collagen fibers were seen in group 1. These findings showed that immunosuppression attenuates aortic dilatation, partly by preserving the collagen fibers, in this rat aneurysm model. Received: September 13, 1999 / Accepted: July 25, 2000