Adriamycin-Lipiodol suspension for i. a. chemotherapy of hepatocellular carcinoma

Summary Physicochemical properties of two types of adriamycin preparation, suspensions and emulsions prepared for i.a. chemotherapy of hepatocellular cacinoma, were investigated. A suspension was prepared by dispersing adriamycin directly into the lipid contrast medium, Lipiodol, whereas an emulsion was obtained by emulsifying an aqueous solution of adriamycin into Lipiodol. The dispersibility of the drug in each preparation was examined microscopically. The chemical stability of and drug release from the preparation were determined by high-performance liquid chromatography and spectrophotometry, respectively. The suspension was then given to ten patients with primary hepatocellular carcinoma. The suspension maintained good dispersibility without coagulation of drug particles, whereas coalescence of aqueous droplets and the resultant phase separation occurred 4 h after preparation of the emulsion. Both preparations maintained the initial drug content for at least 1 week at room temperature. The release of adriamycin was more prolonged in the suspension than in the emulsion. After i.a. administration of the suspension, a selective accumulation of Lipiodol in the tumor and decrease in serum -fetoprotein (AFP) levels were found in most patients. A significant amount of adriamycin was still detected in hepatic speciments resected from two patients 1 and 2 months after treatment. These findings suggest that the adriamycin-Lipiodol suspension may be a useful preparation for targeting chemotherapy to hepatocellular carcinoma.     

Comparative studies in induction of micronuclei by three genetically recombinant and urinary human erythropoietins

Comparative studies on the induction of micronucleated erythrocytesby three recombinant human erythropoietins (rhEPOs) such asepoetin     

Bruceine B, A Potent Inhibitor of Leukocyte-Endothelial Cell Adhesion

Leukocyte adhesion to vascular endothelial cells is an essential step in the development of inflammatory diseases. We have searched for inhibitors of leukocyte-endothelial cell adhesion that could be used as anti-inflammatory drugs and found that bruceine B (0.2 g/ml; 0.44 M) inhibited human neutrophil or T cell adhesion to tumor necrosis factor- (TNF) stimulated human umbilical vein endothelial cells (HUVEC). The inhibition of neutrophil adhesion to TNF-stimulated HUVEC by bruceine B was not derived from cytotoxic effects, as determined by measurement of the level of lactate dehydrogenase (LDH) activity in conditioned medium. The effect of bruceine B on neutrophil adhesion to HUVEC was not seen when the neutrophils were preincubated with bruceine B. However, inhibitory effects were evident when the HUVEC were preincubated with bruceine B. Bruceine B also inhibited neutrophil adhesion to lipopolysaccharide-stimulated HUVEC and T cell adhesion to TNF-stimulated HUVEC. These findings suggest that bruceine B may have anti-inflammatory activity.     

Tumor necrosis factor alpha-gene therapy for an established murine melanoma using RGD (Arg-Gly-Asp) fiber-mutant adenovirus vectors.

Although adenovirus vectors (Ad) provide high-level transduction efficacy to many cell types, extremely high doses of Ad are required for sufficient gene transduction into several tumors, including melanoma. Here, we demonstrated that the expression of coxsackie-adenovirus receptor, a primitive Ad-receptor, was very low in murine and human melanoma cells. We also found that fiber-mutant Ad containing the Arg-Gly-Asp (RGD) sequence in the fiber knob remarkably augmented gene transduction efficacy in melanoma cells by targeting alpha(v)-integrins. In addition, intratumoral injection of RGD fiber-mutant Ad containing the tumor necrosis factor alpha gene (Ad-RGD-TNFalpha) revealed dramatic anti-tumor efficacy through hemolytic necrosis in an established murine B16 BL6 melanoma model. Ad-RGD-TNFalpha required one-tenth the dosage of Ad-TNFalpha to induce an equal therapeutic effect. These results suggest that alpha(v)-integrin-targeted Ad will be a very powerful tool for the advancement of melanoma gene therapy.     

Evaluation of aggressive surgical treatment for advanced carcinoma of the gallbladder

Background/Purpose. An aggressive approach is required to resect advanced carcinoma of the gallbladder. Therefore, an extended surgical procedure often brings about a poor surgical outcome. To test whether an aggressive surgical treatment can improve the survival rate for primary advanced carcinoma of the gallbladder, 59 patients with stage IV primary gallbladder carcinoma were studied. Methods. Patients were divided into three treatment groups for the survival analysis: group A (resectional surgery, n = 29), group B (low-dose cis-diamminedichloroplatinum-II and 5-fluorouracil therapy, n = 10), and group C (exploratory laparotomy, other treatment modalities, or no treatment, n = 20). Results. The prognosis of group A patients was significantly better than that of group B (P = 0.018) or group C (P = 0.0009). Furthermore, group A patients were divided into subgroups. The prognosis of patients resected with no distant metastasis (group A1) was significantly better than that of patients resected with distant metastases of the distant lymph nodes and the liver (group A2) (P = 0.0004). Also, there was no significant difference in the survival rate between the patients resected with distant metastasis (group A2) and chemotherapy cases (group B). Conclusions. These results indicated that radical surgery should be performed for patients with no distant metastasis, and that chemotherapy might be a useful alternative treatment for patients with distant metastasis in advanced carcinoma of the gallbladder.     

Preload-adjusted 2 wave-intensity peaks reflect simultaneous assessment of left ventricular contractility and relaxation.

BACKGROUND: The magnitudes of the first (WI1) and the second wave-intensity peak (WI2) during the ejection period can be used as indices of left ventricular (LV) contractility and relaxation, respectively. However, use of WI to characterize LV dp/dt and the end-diastolic volume (V ed) relationship may be more problematic, as WI may be affected by changes in preload. METHODS AND RESULTS: The LV pressure-volume data sets, consisting of 23 recordings obtained by the conductance method from 12 heart disease patients, were studied. End-systolic elastance (E es) and volume-axis-intercept (V0) were calculated with varying preload. Time constant of LV relaxation (tau), V ed, and WI were calculated from steady-state averaged data. The E es showed a weak correlation with WI1 (r = 0.46, p < 0.05) but a better correlation with preload-adjusted WI1 [WI1/V ed; r=0.86, WI1/V(ed)2; r = 0.92, WI1/(V ed - V0)2; r = 0.89, all p < 0.01]. Similarly, tau did not correlate with WI2 but did correlate with preload-adjusted WI2 [WI2/V ed; r = -0.73, WI2/V(ed) 2; r = -0.63, WI2/(V ed - V0)2; r = -0.78, all p < 0.01]. CONCLUSIONS: These data demonstrate the importance of preload-adjustment when using the WI index for simultaneous assessment of LV contractility and relaxation.     

Mechanisms of acute gain and late lumen loss after atherectomy in different preintervention arterial remodeling patterns

The main mechanism of restenosis after directional coronary atherectomy (DCA) remains obscure. We investigated mechanisms of restenosis after DCA in different coronary artery remodeling patterns. DCA was performed in 51 de novo lesions. The lesions were evaluated by intravascular ultrasound (IVUS) before, immediately after, and 6 months after the procedure. According to the IVUS findings before DCA, we classified the lesions into the following 3 groups: (1) positive (n = 10), (2) intermediate (n = 25), and (3) negative (n = 16) remodeling. We measured lumen area, vessel area, and plaque area using IVUS before DCA, immediately after DCA, and at follow-up. Lumen area increase after DCA was mainly due to plaque area reduction in the positive and intermediate remodeling groups (90 plus minus 15% and 80 plus minus 25% increase in lumen area, respectively), whereas that in the negative remodeling group was due to both plaque area reduction (57 plus minus 22% increase in lumen area) and vessel area enlargement (43 plus minus 33% increase in lumen area). The plaque area increase correlated strongly with late lumen area loss in the positive and intermediate remodeling groups (r = 0.884, p <0.001; r = 0.626, p <0.001, respectively), but the decrease in vessel area was not correlated with lumen area loss. In contrast, both an increase in plaque area and a decrease in vessel area were correlated with late lumen area loss (r = 0.632, p = 0.009; r = 0.515, p = 0.041) in the negative remodeling group. Coronary artery restenosis after atherectomy was primarily due to an increase in plaque in the positive and/or intermediate remodeling groups. However, in the negative remodeling group, late lumen loss might have been caused by both an increase in plaque and vessel shrinkage.     

Prediction of motor outcomes and activities of daily living function using diffusion tensor tractography in acute hemiparetic stroke patients

[Purpose] The efficacy of diffusion tensor imaging in the prediction of motor outcomes and activities of daily living function remains unclear. We evaluated the most appropriate diffusion tensor parameters and methodology to determine whether the region of interest- or tractography-based method was more useful for predicting motor outcomes and activities of daily living function in stroke patients. [Subjects and Methods] Diffusion tensor imaging data within 10 days after stroke onset were collected and analyzed for 25 patients. The corticospinal tract was analyzed. Fractional anisotropy, number of fibers, and apparent diffusion coefficient were used as diffusion tensor parameters. Motor outcomes and activities of daily living function were evaluated on the same day as diffusion tensor imaging and at 1 month post-onset. [Results] The fractional anisotropy value of the affected corticospinal tract significantly correlated with the motor outcome and activities of daily living function within 10 days post-onset and at 1 month post-onset. Tthere were no significant correlations between other diffusion tensor parameters and motor outcomes or activities of daily living function. [Conclusion] The fractional anisotropy value of the affected corticospinal tract obtained using the tractography-based method was useful for predicting motor outcomes and activities of daily living function in stroke patients.Key words: Stroke, Diffusion tensor tractography, Activities of daily living function     

Effect of nicorandil on coronary spasm

In patients in whom dynamic coronary obstruction plays a predominant role in the pathogenesis of angina pectoris, dilatation of large coronary arteries and relief of coronary spasm account for the main mechanism of action of antianginal drugs. In this study, the acute vasodilating effects of nicorandil, a newly developed antianginal drug, were assessed in 10 patients who had spontaneous and ergonovine-evoked coronary spasms. The prompt, complete relief of both spontaneous and evoked coronary spasms was obtained in all of 10 patients with nicorandil. The coronary spasmolytic effect of nicorandil in the present series is thus considered to be beneficial to the treatment of coronary spasm.