Hepatocellular carcinoma: Efficacy of transcatheter oily chemoembolization in relation to macroscopic and microscopic patterns of tumor growth among 100 patients with partial hepatectomy

Purpose: To evaluate the efficacy of transcatheter oily chemoembolization (TOCE) for hepatoceliular carcinoma (HCC) on the basis of microscopic and macroscopic findings postembolization. Methods: HCCs ranging in size from 0.5 to 13 cm (mean 3.6 cm) were obtained from partial hepatectomies of 100 consecutive patients who had undergone TOCE between 20 and 246 days (mean 59.5 days) prior to surgery. The efficacy of TOCE was assessed on the basis of the necrotic to live cell ratio of the tumors. The microscopic pattern of tumor growth was grouped into expanding type (complete capsule formation) and replacing type (incomplete or no capsule). There were five types of macroscopic groupings: single nodule, single nodule with extranodular growth (SNE), contiguous and noncontiguous multinodular, and massive growth type. Results: Among 79 cases with the expanding type, 29 (37%) had 100% HCC necrosis, but none with 100% necrosis were in the replacing type. By macroscopic grouping, the efficacy of TOCE decreased from the single nodule type (50% of patients had 100% necrosis) to the SNE type (21%), and the other types (9%).     

Reversal of multidrug resistance by new dihydropyridines with lower calcium antagonistic activity

Summary BS compounds, a series of new dihydropyridines, successfully overcame multidrug resistance in P388/ADR cells in vitro. These agents synergistically potentiated the cytotoxicity of Adriamycin to P388/ADR cells at a concentration of 1–2 M, whereas they showed hardly any synergistic effect in the parental cell line (P388/S) at the same concentration. They inhibited the active drug efflux in P388/ADR cells as well as the binding of [G-³H]-vinblastine to membrane vesicles from P388/ADR, which was increased in resistant P388 cells as compared with parental cells. Besides, unlike the activity of clinically used calcium antagonists, the calcium antagonistic activity associated with BS compounds was very weak: their arterial relaxation activity was <21% of that of verapamil. These data suggest that BS compounds specifically overcome multidrug resistance without the serious hypotensive side effects that accompany the use of verapamil orother calcium antagonists.     

Bacteriological, pharmacokinetic and clinical studies on clarithromycin in the pediatric field. Pediatric Study Group of Clarithromycin

Clarithromycin (TE-031, A-56268), a new macrolide antibiotic agent, was evaluated bacteriologically and clinically for its efficacy and safety in pediatrics by a study group organized with pediatricians from all over the country. A summary of the results of the evaluation is as follows. 1. Absorption and excretion Pharmacokinetics of TE-031 was examined by single oral administration of 10% granules and 50 mg tablets at doses of 1, 5, 10 and 15 mg/kg. There were no significant differences between 10% granules and 50 mg tablets, and between administrations before and after meal. Peaks and half-life periods of blood level of TE-031 given once at doses of 5, 10 and 15 mg/kg (10% granules) before meal were 1.58, 4.37 and 3.79 micrograms/ml, and 2.53, 3.17 and 2.20 hours, respectively, and the urinary excretion in 6 hours after the administration were about 20-30%. 2. Antibacterial effects TE-031 was proved to have excellent antibacterial effect, i.e., inhibiting growth over 80% of strains of Streptococcus pneumoniae and Streptococcus pyogenes at 0.10 micrograms/ml, Branhamella catarrhalis at 0.39 micrograms/ml, and Campylobacter jejuni at 0.78 micrograms/ml. Against Staphylococcus aureus, TE-031 showed very similar activity spectrum to EM, and EM resistant strains were also resistant to TE-031. 3. Clinical results A total of 764 cases was studied. Clinical effects of TE-031 were evaluated in 717 cases out of the 764, excluding drop-outs and cases which did not meet specified protocols. Clinically, efficacies of TE-031 were "excellent" in 265 cases and "good" in 161 cases out of 453 cases of Group A in which causal agents were identified, with an efficacy rate of 94.0%, and out of 264 cases of Group B in which pathogens were not detected, clinical effects of TE-031 were "excellent" in 115 cases and "good" in 124 cases, with an efficacy rate of 90.5%. In terms of clinical effects of TE-031 classified by diseases when Group A and B were combined, efficacy rates were 91.6% for upper respiratory tract infection (217/237), 90.0% for bacterial pneumonia (108/120), 97.4% for Mycoplasma pneumonia (111/114), 100% for Chlamydia pneumonia (4/4), 85.0% for pertussis (34/40), 100% for scarlet fever (16/16), 83.9% for skin and soft tissue infection (26/31), and 98.9% for Campylobacter enteritis (87/88).(ABSTRACT TRUNCATED AT 400 WORDS)     

MR imaging of renal cell carcinoma: associations among signal intensity, tumor enhancement, and pathologic findings

The purpose of this study was to compare the MR characteristics of renal cell carcinomas against histologic findings and to assess the correlations among signal intensity, tumor enhancement, and pathologic findings. Fifty-four patients (56 lesions) were examined by MR imaging and then underwent partial or radical nephrectomy. The pathologic diagnosis of all lesions was renal cell carcinoma. All MR examinations were performed as dynamic studies using the same 1.5-T scanner. MR characteristics were compared against pathologic findings after resection, and the correlations among signal intensity, tumor enhancement, and pathologic findings were then assessed. A significant correlation was observed between tumor grade and tumor enhancement, with G3 lesions tending to show little enhancement. Regardless of the histologic classification, G3 tumors were found to contain highly heterotypic cancer cells and very few vessels by histopathologic examination. No significant correlations were noted between the other MR characteristics and pathologic findings. Renal cell carcinomas showing little enhancement tend to be highly malignant lesions based on the pathologic findings. Special consideration is required for these tumors with regard to the selection of surgical intervention and follow-up observation.     

Toll-like receptor 9 is expressed on follicle-associated epithelia containing M cells in swine Peyer's patches

The precise distribution and expression of Toll-like receptor (TLR) 9 in gut-associated lymphoid tissues (GALTs) has not been elucidated. In this study, we investigated the expression pattern of TLR9 in adult and neonatal swine GALTs by real-time quantitative PCR, western blot, confocal laser microscopy and flow cytometric analysis. The swine TLR9 gene was preferentially expressed in adult Peyer's patches (Pps) and mesenteric lymph nodes (MLNs), which contained approximately three times higher TLR9 than the spleen. Other tissues exhibited only weak expression of TLR9. In neonatal swine, elevated expression of TLR9 was detected only in MLNs. We firstly showed that highly expressive (TLR9(+)) cells were formed in Pps and MLNs. In addition, TLR9(+) cells were present not only in immune cells such as dendritic cells and B cells but also in follicle-associated epithelia (FAE) including membranous cells (M cells) in Pps. These results suggest that Pps and MLNs provide the host defense with the ability to respond to a variety of bioactive oligonucleotides (ODNs) from bacteria at a conductive site of initial immune responses.     

Reduced-intensity unrelated cord blood transplantation for patients with advanced malignant lymphoma.

We report the results of reduced-intensity unrelated cord blood transplantation (RI-UCBT) in patients with advanced malignant lymphoma. Twenty patients (median age, 46.5 years; range, 27-66 years) underwent RI-UCBT with a preparative regimen consisting of fludarabine 125 mg/m2 , melphalan 80 mg/m 2 , and 4 Gy of total body irradiation. The median infused total cell dose was 2.75 x 10(7)/kg (range, 2.3-3.4 x 10(7)/kg). Graft-versus-host disease (GVHD) prophylaxis was composed of cyclosporine or tacrolimus alone. Fifteen patients achieved primary neutrophil engraftment after a median of 20 days. Eight patients developed grade II to IV acute GVHD, and 2 developed chronic GVHD. Of the 16 patients with evaluable disease, 10 achieved a complete response. Primary disease recurred in 1 patient, and transplant-related mortality within 100 days occurred in 8 of 20 patients. The estimated 1-year probability of progression-free survival was 50%. These data suggest that RI-UCBT is a feasible option for patients with refractory lymphoma who lack an HLA-matched donor.     

Advance in animal experiments with the undulation pump total artificial heart: 50 and 54 day survival periods with 1/R control

The undulation pump total artificial heart (UPTAH) is a unique, implantable, total artificial heart (TAH) that uses undulation pumps. To achieve long-term survival in animals with physiologic hemodynamic conditions, a control method based on conductance and arterial pressure was applied to UPTAH. With this control method, called 1/R control, survival periods of 50 days (No. 0016, 49.6 kg) and 54 days (No. 0030, 42.5 kg) were obtained in adult female goats. In No. 0016, 1/R control was applied to the left pump, whereas in No. 0030, it was applied to the right pump. Another pump was used for left-right balance control. The control stability was better in No. 0030 than in No. 0016. The sucking effect of the left atrium was remarkable in No. 0016, possibly because of a time delay when left-right balance control was performed with the right pump. In No. 0016, the cause of death was probably a thrombus flown from a panus in the left atrium. It is possible that the left atrial suction effect influenced the thrombus and panus formation in the left atrium. In No. 0030, the cause of death was a small rupture of the membrane in the right pump. The rupture may have been caused by excessive negative pressure inside the pump. This pressure resulted from suction of the right atrium because of an unexpected control excursion, which was probably caused by a software bug. It will be necessary to redesign the undulation pump and improve the software to achieve longer survival periods for animals with physiologic hemodynamic conditions.     

No association between the Pro197Leu polymorphism in the glutathione peroxidase (GPX1) gene and schizophrenia

OBJECTIVE: Oxidative stress such as free radical-mediated neuronal dysfunction may be involved in the pathophysiology of schizophrenia. The human glutathione peroxidase (GPX1) is a selenium-dependent enzyme, which plays an important role in the detoxification of free radicals. We therefore hypothesized that the GPX1 gene, which is located on chromosome 3p21.3, may be involved in the pathophysiology of schizophrenia. The aim of this study is to examine whether a potentially functional polymorphism, a proline (Pro) to leucine (Leu) substitution at codon 197 (Pro197Leu) of the human GPX1 gene, is associated with susceptibility to schizophrenia. METHODS: We genotyped the Pro197Leu polymorphism in a total of 113 nuclear families that had a proband with schizophrenia. Genetic association was tested using the transmission disequilibrium test (TDT), the sib transmission disequilibrium test (STDT), and the family-based association test (FBAT). RESULTS: The minor allele (Leu) frequency was calculated to be 0.282. We could not find significant transmission disequilibrium of the alleles for the Pro197Leu polymorphism in the GPX1 gene in association with the presence of schizophrenia in our family sample (TDT, chi2=0.03, degrees of freedom=1, P=0.86; combined TDT-STDT, Z'=-0.052, P=0.47; FBAT, Z=0.000, P=1.000). CONCLUSION: The results of this study suggest that the GPX1 polymorphism is unlikely to be associated with susceptibility to schizophrenia.