A mixture of ethylene vinyl alcohol copolymer and ethanol yielding a nonadhesive liquid embolic agent to treat cerebral arteriovenous malformations: initial clinical experience

OBJECT: The authors report their clinical experience with their new nonadhesive liquid embolic agent, an ethylene vinyl alcohol copolymer (EVAL)/ethanol mixture, to treat arteriovenous malformations (AVMs). METHODS: Between June 1995 and April 2001, 57 patients with confirmed AVMs underwent embolization of their lesions with the EVAL/ethanol mixture. In 87 procedures consisting of one to three stages, the authors embolized 185 feeding arteries to occlude as much of the AVM as possible. Repeated injections under fluoroscopic control could be performed smoothly without encountering cementing of the catheter to the vessel wall. Among the 87 embolizations undertaken in 57 patients, seven procedures (8%) in six patients produced new postembolization symptoms. Resolution of these symptoms occurred within hours or days after four of the seven procedures; permanent neurological deficits remained after the other three procedures (3.4%). Of the 57 patients, three underwent postembolization radiosurgery, and 54 underwent radical treatment with microsurgical extirpation. Histopathological examination of the 54 specimens disclosed mild inflammation within the embolized lumen without inflammatory reactions in the media or adventitia. Follow-up angiograms obtained 3 years after radiosurgery was administered showed that in all three patients treated in this fashion the nidus had completely disappeared. CONCLUSIONS: The EVAL/ethanol mixture is handled easily and appears to be an effective and safe agent for preoperative embolization of AVMs.     

A nonadhesive liquid embolic agent composed of ethylene vinyl alcohol copolymer and ethanol mixture for the treatment of cerebral arteriovenous malformations: experimental study

OBJECT: The authors have developed a mixture of ethylene vinyl alcohol copolymer (EVAL) and iopamidol, which is dissolved in ethanol, as an alternative solvent to provide a safe means of embolizing arteriovenous malformations (AVMs). METHODS: A two-stage delivery technique is required to prevent premature precipitation in the catheter when using this material: the catheter is first infused with 30% ethanol and this is followed by the delivery of the EVAL-ethanol mixture. Acute angiographic changes were analyzed after superselective delivery of dimethyl sulfoxide (DMSO) and 30% ethanol into the renal artery of rabbits. Histological changes following the embolization of the renal artery achieved using the EVAL-ethanol mixture were recorded at 1 hour and at 2 and 16 weeks after the procedure. Although DMSO always produced severe, rapidly progressive vasospasm in the renal artery during a 1- to 60-minute postinfusion, 30% ethanol did not. Microscopically, the lumens of embolized vessels examined 1 hour after embolization with EVAL-ethanol appeared to be filled with EVAL sponges, leaving almost no open spaces. The space between the EVAL sponges and the inner surface of the vessels was filled with fresh thrombus. In the vessel walls of specimens examined 2 weeks after embolization there was no or a slight inflammatory reaction. Scattered in the EVAL sponges were almost equal numbers of neutrophilic granulocytes and mononuclear cells, indicative of a mild inflammatory response. In specimens examined 16 weeks postembolization, the changes noted at 2 weeks were intensified. There was no definite histopathological evidence of mural hemorrhage, perivascular extravasation of the mixture, or perivascular hemorrhage in any specimen that was examined. CONCLUSIONS: Although the degree of permanence of this embolization material is yet unknown, the mixture was easy to handle, and appeared safe and effective for AVM embolization. Its nonadhesive characteristic and its ability to be infused by repeated injections make it an attractive alternative to currently available materials. The good results obtained in this study led us to undertake a clinical trial, the results of which are contained in a companion article in this issue of the Journal of Neurosurgery.     

Effects of social support on the mental health of mothers with infants

OBJECTIVE: We surmised that increase in stress in mothers having infants might be due to decline of social support under circumstances where nuclear family households now predominate. The present study was therefore conducted to analyze relations between stress reactions of mothers having infants, their recognition of social support, and negative feelings toward their baby and child care, a major factor in the burden of childcare. METHODS: The subject were 909 mothers having infants in nuclear families who lived in I city in Osaka Prefecture. Health examinations of infants at the ages of 4 months, 1 year and 6 months, and 3 years and 6 months were utilized. Questionnaires titled "Survey on Childcare" were distributed in advance by mail to parents of the infants included in the health examinations and collected at the health examinations. The survey period was August to September 2000. Personal background variables and, psychological investigation items, including mental health in terms of stress reactions, negative feelings toward childcare as a factor in the burden of childcare, and a support network scale were surveyed and analyzed. RESULTS: The mothers with infants were judged to be in a stressful state from the average mental health scores in all groups. Multiparas had significantly higher negative feelings toward childcare scores. Regarding the age groups of children, a significantly decreasing recognition of a support network as well as significantly increasing negative feelings toward childcare were observed with the growth of children. There was a positive correlation between negative feelings toward childcare and stress reactions. The recognition of social support was negatively correlated with stress reactions and negative feelings toward childcare. CONCLUSION: The study revealed that mothers having infants are in a stressful state and that the recognition of stress is related to negative feelings toward childcare and the recognition of a support network. The feeling of sufficient support lowers the level of stress arising from childcare, and facilitates avoiding or coping with problems, thereby promoting mothers' physical and mental health. This is important for continuation and fulfillment of childcare.     

Dosimetry of fission neutrons in a 1-W reactor,UTR-KINKI

The energy spectrum of fission neutrons in the biological irradiation field of the Kinki University reactor, UTR-KINKI, has been determined by a multi-foil activation analysis coupled with artificial neural network techniques and a Au-foil activation method. The mean neutron energy was estimated to be 1.26 +/- 0.05 MeV from the experimentally determined spectrum. Based on this energy value and other information, the neutron dose rate was estimated to be 19.7 +/- 1.4 cGy/hr. Since this dose rate agrees with that measured by a pair of ionizing chambers (21.4 cGy/hr), we conclude that the mean neutron energy could be estimated with reasonable accuracy in the irradiation field of UTR-KINKI.     

Preoperative cytodiagnosis of very small-sized peripheral-type primary lung cancer

To demonstrate the importance of preoperative diagnosis of pulmonary cancers presenting as peripheral small-sized solitary shadows we evaluated the results of morphologic definitive diagnosis together with various clinical factors in 91 tumors with less than 15-mm diameter resected surgically between 1983 and 1999. Histologically, these tumors consisted of 73 adenocarcinomas, nine squamous cell carcinomas, and nine other types. Regarding the pathologic stage, 57 tumors were classified in stage IA, three in IB, six in IIA, seven in IIIA, 14 in IIIB, and four in IV. Comparing various biopsy techniques, the sensitivity of preoperative cytodiagnosis was 43.7% for transbronchial brushing (n = 48), 52.9% for transbronchial forceps biopsy-stamp cytology (n = 51), 66.6% for transbronchial fine needle aspiration (n = 78), and 85.0% for percutaneous fine needle aspiration (n = 20). The overall sensitivity of preoperative cytodiagnosis was 79.0% for transbronchial biopsy (n = 81), and 87.3% for transbronchial and percutaneous biopsy (n = 87). Of 73 clinical N0 cases in which lobectomy was performed, 10 cases (13.6%) were diagnosed as between pathological degrees N1, N2 and N3. However, lung cancer cases with less than 10-mm diameter did not have lymph node metastasis. Our study of histologic differentiation showed that all cases of well-differentiated adenocarcinomas (n = 20) were pathological degree N0. The overall sensitivity of preoperative diagnosis increased to 89.1% in cases (n = 74) of tumors with 11-15-mm diameter. The sensitivity of cytodiagnosis for peripheral small-sized primary lung cancers is high, and we can estimate histological differentiation based on the cytological findings. Therefore, cytodiagnosis is an effective and indispensable diagnostic method for determination of the optimal treatment approach, including approaches such as intentionally limited resection.     

Phase I trial of weekly docetaxel in elderly patients with non-small cell lung cancer

Recent experience with weekly administration of docetaxel has demonstrated less myelotoxicity and suggested that this regimen holds promise for elderly patients at the high risk of myelosuppression. However, in this phase I trial of weekly docetaxel conducted only in elderly patients (70 years old or more) with non-small cell lung cancer (NSCLC), the toxicity profile was markedly different from that in previous reports. The dose-limiting toxicities were neutropenia, diarrhea and infection, all of which were observed at a dose of 30 mg/m(2)/week and the maximum-tolerated dose by protocol definition was 30 mg/m(2)/week. Although other hematological and non-hematological toxicities observed in this treatment were generally moderate and were well tolerated by elderly patients with NSCLC, the risk of myelosuppression still requires careful attention.     

Cancer chemopreventive effect of quassinoid derivatives. Introduction of side chain to shinjulactone C for enhancement of inhibitory effect on Epstein-Barr virus activation

A series of shinjulactone C (1) derivatives (2-8) were synthesized and evaluated for their anti-tumor promoting effects against Epstein-Barr virus early antigen activation introduced by 12-O-tetradecanoylphorbol-13-acetate in Raji cells. The succinate and 3',3'-dimethylsuccinate derivatives of 1 exhibited higher inhibitory effects than 1. From the point of view of structure-activity relationships, the succinate derivatives (2, 4) demonstrated better potency than the glutarate derivatives (3, 5-8). As substituted moieties of 3'-position became bulky, the inhibitory effects of the glutarate derivatives (7, 8) significantly decreased.     

Werner and Bloom helicases are involved in DNA repair in a complementary fashion

Werner syndrome (WS) is a recessive disorder characterized by premature senescence. Bloom syndrome (BS) is a recessive disorder characterized by short stature and immunodeficiency. A common characteristic of both syndromes is genomic instability leading to tumorigenesis. WRN and BLM genes causing WS and BS, encode proteins that are closely related to the RecQ helicase. We produced WRN-/-, BLM-/- and WRN(-/-)/BLM(-/-) mutants in the chicken B-cell line DT40. WRN-/- cells showed hypersensitivities to genotoxic agents, such as 4-nitroquinoline 1-oxide, camptothecin and methyl methanesulfonate. They also showed a threefold increase in targeted integration rate of exogenous DNAs, but not in sister chromatid exchange (SCE) frequency. BLM-/- cells showed hypersensitivities to the genotoxic agents as well as ultraviolet (UV) light, in addition to a 10-fold increase in targeted integration rate and an 11-fold increase in SCE frequency. In WRN(-/-)/BLM(-/-) cells, synergistically increased hypersensitivities to the genotoxic agents were observed whereas both SCE frequencies and targeted integration rates were partially diminished compared to the single mutants. Chromosomal aberrations were also synergistically increased in WRN(-/-)/BLM(-/-) cells when irradiated with UV light in late S to G(2) phases. These results suggest that both WRN and BLM may be involved in DNA repair in a complementary fashion.     

Involvement of IL-2/IL-2R system activation by parasite antigen in polyclonal expansion of CD4(+)25(+) HTLV-1-infected T-cells in human carriers of both HTLV-1 and S. stercoralis

The intermediate state of HTLV-1 infection, often found in individuals dually infected with Strongyloides stercoralis (S. stercoralis) and HTLV-1, is assumed to be a preleukemic state of adult T-cell leukemia (ATL). To investigate the effects of S. stercoralis superinfection on the natural history of HTLV-1 infection, we characterized peripheral blood samples of these individuals in Okinawa, Japan, an endemic area for both HTLV-1 and S. stercoralis and we studied effects of the parasite antigen on T-cells. The dually infected individuals showed a significantly higher provirus load and an increase in CD4(+)25(+) T cell population, with a significant, positive correlation. This increase was attributable to polyclonal expansion of HTLV-1-infected cells, as demonstrated by inverse-long PCR analysis of the integration sites. S. stercoralis antigen activated the IL-2 promoter in reporter gene assays, induced production of IL-2 by PBMC in vitro, and supported growth of IL-2 dependent cell lines immortalized by HTLV-1 infection or the transduction of Tax. Taken collectively, these results indicate that S. stercoralis infection induces polyclonal expansion of HTLV-1-infected cells by activating the IL-2/IL-2R system in dually infected carriers, an event which may be a precipitating factor for ATL and inflammatory diseases.     

Localization of p0071-interacting proteins,plakophilin-related armadillo-repeat protein-interacting protein (PAPIN) and ERBIN,in epithelial cells

PAPIN has six PDZ domains and interacts with p0071, a catenin-related protein. Recent studies have revealed that catenins determine the subcellular localization of some PDZ proteins. We have examined whether the localization of PAPIN is determined by p0071 in epithelial cells. PAPIN was localized not only on the lateral membrane but also on the apical membrane, where p0071 was absent. The targeting to both membranes was mediated by the middle region of PAPIN and did not require the p0071-interacting PDZ domain. In cells that came into contact, PAPIN was diffusely distributed on the plasma membrane, while p0071 was concentrated at immature cell-cell contacts. When epithelial cells were exposed to the low concentration of calcium, p0071 was internalized, whereas PAPIN remained on the plasma membrane. We also confirmed that the interaction with p0071 was not essential for the membrane targeting of ERBIN, a recently identified p0071- and ErbB2-binding protein. PAPIN, p0071, and ERBIN formed a complex in 293T cells. Furthermore, ERBIN and ErbB2 were colocalized with PAPIN on the lateral membrane. These findings suggest that PAPIN, p0071, and ERBIN come to the cell-cell contacts independently and interact with each other on the lateral membrane.