Significance of histologic pattern of carcinoma and sarcoma components on survival outcomes of uterine carcinosarcoma.

BACKGROUND: To examine the effect of the histology of carcinoma and sarcoma components on survival outcome of uterine carcinosarcoma. PATIENTS AND METHODS: A multicenter retrospective study was conducted to examine uterine carcinosarcoma cases that underwent primary surgical staging. Archived slides were examined and histologic patterns were grouped based on carcinoma (low-grade versus high-grade) and sarcoma (homologous versus heterologous) components, correlating to clinico-pathological demographics and outcomes. RESULTS: Among 1192 cases identified, 906 cases were evaluated for histologic patterns (carcinoma/sarcoma) with high-grade/homologous (40.8%) being the most common type followed by high-grade/heterologous (30.9%), low-grade/homologous (18.0%), and low-grade/heterologous (10.3%). On multivariate analysis, high-grade/heterologous (5-year rate, 34.0%, P = 0.024) and high-grade/homologous (45.8%, P = 0.017) but not low-grade/heterologous (50.6%, P = 0.089) were independently associated with decreased progression-free survival (PFS) compared with low-grade/homologous (60.3%). In addition, older age, residual disease at surgery, large tumor, sarcoma dominance, deep myometrial invasion, lymphovascular space invasion, and advanced-stage disease were independently associated with decreased PFS (all, P < 0.01). Both postoperative chemotherapy (5-year rates, 48.6% versus 39.0%, P < 0.001) and radiotherapy (50.1% versus 44.1%, P = 0.007) were significantly associated with improved PFS in univariate analysis. However, on multivariate analysis, only postoperative chemotherapy remained an independent predictor for improved PFS [hazard ratio (HR) 0.34, 95% confidence interval (CI) 0.27-0.43, P < 0.001]. On univariate analysis, significant treatment benefits for PFS were seen with ifosfamide for low-grade carcinoma (82.0% versus 49.8%, P = 0.001), platinum for high-grade carcinoma (46.9% versus 32.4%, P = 0.034) and homologous sarcoma (53.1% versus 38.2%, P = 0.017), and anthracycline for heterologous sarcoma (66.2% versus 39.3%, P = 0.005). Conversely, platinum, taxane, and anthracycline for low-grade carcinoma, and anthracycline for homologous sarcoma had no effect on PFS compared with non-chemotherapy group (all, P > 0.05). On multivariate analysis, ifosfamide for low-grade/homologous (HR 0.21, 95% CI 0.07-0.63, P = 0.005), platinum for high-grade/homologous (HR 0.36, 95% CI 0.22-0.60, P < 0.001), and anthracycline for high-grade/heterologous (HR 0.30, 95% CI 0.14-0.62, P = 0.001) remained independent predictors for improved PFS. Analyses of 1096 metastatic sites showed that carcinoma components tended to spread lymphatically, while sarcoma components tended to spread loco-regionally (P < 0.001). CONCLUSION: Characterization of histologic pattern provides valuable information in the management of uterine carcinosarcoma.

Impact of multimodal therapy on the survival of patients with newly diagnosed uterine carcinosarcoma.

PURPOSE: To investigate treatment outcomes of uterine carcinosarcoma (CS) patients who underwent complete surgical resection of all visible disease and platinum-based adjuvant chemotherapy (multimodal therapy). MATERIALS AND METHODS: The authors reviewed 127 uterine CS patients treated at this institution from 1990 to 2010. They operated 123 patients in clinical Stages 1-3, 97 of which underwent complete resection and systemic lymphadenectomy. RESULTS: A total of 97 patients (FIGO 2008: Stage 1 in 50 patients, Stage 2 in six, Stage 3 in 37, and Stage 4 in four) underwent surgical staging, 74 of which were administered five cycles (median) of platinum-based adjuvant chemotherapy. The median overall survival (OS) associated with multimodal therapy 50.6 months compared with 34.9 months incomplete multimodal therapy. After multimodal treatment, 32.9% (32/97) patients showed recurrence (24/32 hematogenous). CONCLUSION: Multimodal therapy increased survival among uterine CS patients, but the recurrence rate remained high. Further consideration of treatment options for uterine CS is required.

Locoregional mitomycin C injection for esophageal stricture after endoscopic submucosal dissection.

This prospective study aimed to evaluate the feasibility and safety of locoregional mitomycin C (MMC) injection to treat refractory esophageal strictures after endoscopic submucosal dissection (ESD) for superficial esophageal carcinoma. Patients with dysphagia and strictures that were refractory to repeated endoscopic balloon dilation (EBD) were eligible. After EBD, MMC was injected into the dilated site. Between June 2009 and August 2010, five patients were recruited. The treatment was performed once in two patients and twice in three patients with recurrent dysphagia or restenosis. In all patients, passing a standard endoscope through the site was easy and the dysphagia grade improved (grade 3→1 in 3 patients, grade 4→2 in 2 patients). No serious complications were noted. During the observation period of 4.8 months, neither recurrent dysphagia nor re-stricture appeared in any of the patients. The combination of locoregional MMC injections and EBD is feasible and safe for the treatment of esophageal strictures after ESD.Recently, endoscopic submucosal dissection (ESD) has been developed and accepted as a new endoscopic treatment for gastrointestinal tumors. ESD is a promising treatment for superficial esophageal carcinoma (SEC), and it has a reliable en bloc resection rate. However, the application of ESD for widespread lesions is challenging because of the high risk of the development of severe strictures, which lead to a low quality of life after ESD. Although endoscopic balloon dilation (EBD) is effective for benign strictures, it needs to be performed frequently until the dysphagia disappears 1. Mitomycin C (MMC), which is a chemotherapeutic agent derived from some Streptomyces species 2, reduces scar formation when topically applied to a surgical lesion. MMC has been applied to treat strictures in a variety of anatomical locations, including a variety of organs 3. The aim of this study was to prospectively evaluate both the feasibility and the safety of locoregional MMC injection therapy in patients with refractory esophageal strictures after ESD for SEC.

[Rib-originated fibrous dysplasia: report of a case].

The incidence of fibrous dysplasia (FD) is not frequent in the case of benign bone tumors of the chest wall, and differential diagnosis between FD and the malignancy on the basis of imaging findings is difficult. We report a case of a painful FD lesion (size, 9×8 cm) that originated from the 5th rib of a 52-year-old man and was surgically resected. His symptoms improved after the operation. Painful and large FD lesions should be resected because of a difficulty in differential diagnosis from malignant tumors.

Significance of uterine corpus tumor invasion in early-stage cervical cancer.

OBJECTIVE: To examine characteristics and survival outcomes of women with surgically-treated cervical cancer exhibiting uterine corpus tumor invasion. METHODS: We utilized The Surveillance, Epidemiology, and End Results Program to identify cervical cancer patients who underwent hysterectomy between 1973 and 2003. Logistic regression models were used to identify risk factors for uterine corpus tumor invasion on multivariable analysis. Association of uterine corpus tumor invasion and cause-specific survival (CSS) from cervical cancer was examined with Cox proportional hazard regression models on multivariable analysis. RESULTS: We identified 837 (4.9%) cases of uterine corpus invasion and 16,237 (95.1%) cases of non-invasion. Median follow-up time was 14.0 years. There were 1642 deaths due to cervical cancer. Uterine corpus invasion was independently associated with older age, non-squamous histology, high-grade tumors, large tumor size, and nodal metastasis on multivariable analysis (all, P < 0.001). On univariable analysis, uterine corpus tumor invasion was significantly associated with decreased CSS compared to the non-invasion (5-year rates, 79.0% versus 94.5%, P < 0.001). After controlling for other significant prognostic factors, uterine corpus tumor invasion remained an independent prognostic factor for decreased CSS (adjusted-hazard ratio 1.45, 95% confidence interval 1.21-1.74). Among stage T1b cases (n = 6730), uterine corpus tumor invasion remained an independent prognostic factor for decreased CSS (adjusted-hazard ratio 1.95, 95%CI 1.47-2.60). Uterine corpus tumor invasion was significantly associated with decreased CSS in stage T1b1 disease (74.5% versus 90.7%, P < 0.001) and in stage T1b2 disease (67.0% versus 79.5%, P = 0.01). CONCLUSION: Uterine corpus tumor invasion is an independent prognostic factor for decreased survival of women with early-stage cervical cancer.

Effect of stilbenedisulfonate binding on the state of association of the membrane-spanning domain of band 3 from bovine erythrocyte membrane.

The membrane-spanning domain of bovine band 3, the anion transport protein of erythrocyte membrane, was purified in the presence of nonaethyleneglycol lauryl ether (C12E9) and the effect of a covalent attachment of 4,4'-diisothiocyanostilbene-2,2'-disulfonate (DIDS), a potent transport inhibitor, on the state of association of the domain isolated (the 58 kDa fragment) was studied via gel filtration, gel electrophoresis and sedimentation velocity experiments. It was indicated that the DIDS-unlabeled fragment in C12E9 solution forms heterogeneous aggregates which are larger in size than the dimer. This contrasted with the behavior that bovine band 3 is present as dimers or tetramers in the same medium (Nakashima and Makino (1980) J. Biochem. 88, 933-947). When DIDS was covalently attached, the fragment was present as a single molecular species which was indicated to be a dimer by molecular weight determination. The secondary structure of the fragment was not affected by DIDS. The change in the state of association caused by the DIDS-binding was also found in the presence of sucrose monolaurate (SE12), which was a more potent detergent for extraction of the 58 kDa fragment from membranes than C12E9. However, the complex with SE12 was extremely unstable.

Oxidation of acetylpolyamines by extracellular polyamine oxidase produced by Penicillium sp. No. PO-1.

The oxidation of acetylpolyamines by an extracellular polyamine oxidase of Penicillium sp. No. PO-1 was investigated. The optimal pH value for oxidation of acetylpolyamines was 6.0. The purified enzyme oxidized spermidine, spermine, N1-acetylspermidine, N8-acetylspermidine, N1,8-diacetylspermidine, N1-acetylspermine and N1,12-diacetylspermine. The relative velocities for oxidation of acetylpolyamines were lower than those of spermidine and spermine. The Km values for oxidation of acetylpolyamines were higher than those of spermidine and spermine. The enzyme split N1-acetylspermidine and N8-acetylspermidine at the same position of the linkage as in spermidine oxidation. N1-Acetylspermine was changed to N1-acetylspermidine. This oxidation mechanism was different from that of rat liver polyamine oxidase. N1-Acetylspermine inhibited the oxidation of spermine. Putrescine, N8-acetylspermidine and N1,12-diacetylspermine also inhibited the N1-acetylspermidine oxidation by the enzyme.

Molecular cloning and analysis of the 5'-flanking region of the human MYPT1 gene.

We have cloned and sequenced a 5 kb genomic fragment in the 5'-flanking region of the human myosin phosphatase target subunit 1. The transcription initiation site (+1) was 268 bp upstream from the translation start site. In this promoter there are no canonical TATA or CAAT box elements but there is a high GC-rich sequence. Basal promoter activity was due to the GC-rich region that contained one Sp1 transcription factor binding site, thus demonstrating that the MYPT1 gene is a housekeeping gene. Luciferase reporter assays showed the presence of two regions for positive elements and one for a negative element.

Prevention of human T cell lymphotropic virus type I infection in Japanese macaques by passive immunization.

Prophylaxis against human T cell lymphotropic virus type I (HTLV-I) is of primary importance for the eradication of adult T cell leukemia and other diseases associated with this virus. Hyperimmune globulin (H-IgG) prepared from healthy blood donors with high antibody titers for HTLV-I was evaluated for its prophylactic effect against HTLV-I in Japanese macaques (Macaca fuscata). Normal IgG (N-IgG) prepared from seronegative healthy blood donors was used as control. Both preparations contained 50 mg/ml IgG and H-IgG had a neutralizing antibody titer of 1:7100 by vesicular stomatitis virus (HTLV-I) pseudotype neutralization assay. Two macaques were infused with 2 ml/kg N-IgG and three macaques were immunized with 2-0.5 ml/kg H-IgG. They were immediately challenged by inoculation of 8 x 10(6)/kg cells from an HTLV-I-producing rabbit lymphoid cell line (Ra-1). Another macaque was immunized with 1 ml/kg H-IgG 24h after inoculation of 8 x 10(6)/kg Ra-1 cells. HTLV-I infection, as determined by seroconversion and verified by polymerase chain reaction, occurred in both of the N-IgG-injected macaques but in none of the four H-IgG-injected macaques. These results demonstrate the protective efficacy of H-IgG against HTLV-I infection in a primate model and provide an experimental basis for passive immunization trials in humans.

Efficacy of imidacloprid/permethrin and fipronil/(S)-methoprene combinations against Haemaphysalis longicornis ticks evaluated under in vitro and in vivo conditions.

Haemaphysalis longicornis is one of the most important ticks infesting a wide range of mammals including dogs in Japan. H. longicornis is recorded to be a vector of, for example, Babesia gibsoni. It was the aim of the study presented here to evaluate the efficacy of imidacloprid/permethrin and fipronil/(S)-methoprene against larval, nymphal and adult stages of H. longicornis under in vitro as well as in vivo conditions. In the in vitro part of the study, ticks showed avoidance behaviour to imidacloprid/permethrin-treated filter papers. The onset of acaricidal efficacy in the imidacloprid/permethrin group was recorded earlier than in the fipronil/(S)-methoprene group. In the in vivo experiment three beagles per group were treated with either imidacloprid/permethrin, fipronil/(S)-methoprene or left untreated. Each dog was infested with 30 adult female H. longicornis. Ticks were place on a shaved area of skin of the treated dogs and behaviour of the ticks was recorded as before. After 3 h all ticks were removed and placed in Petri dishes. Ticks were further examined until day 4 post-treatment (p.t.). All ticks recovered from the untreated dogs survived. At 4 h p.t. (1 h post-removal) 40 of the 90 ticks exposed to the imidacloprid/permethrin treatment and 25 of the 90 ticks in the fipronil/(S)-methoprene-treated group were found dead. At day 1 p.t., 61 ticks in the imidacloprid/permethrin- and 81 ticks in the fipronil/(S)-methoprene-treated group were recorded dead. At the final examination day 4 p.t., all 90 ticks were found dead in the imidacloprid/permethrin group, while five ticks remained alive in the fipronil/(S)-methoprene group.

Nucleosides and nucleotides. 107. 2-(cycloalkylalkynyl)adenosines: adenosine A2 receptor agonists with potent antihypertensive effects.

Adenosine receptor-binding profiles in rat brain tissues and antihypertensive effects in spontaneously hypertensive rats (SHR) of a series of 2-(cycloalkylalkynyl)adenosines (2-CAAs) and their congeners are described. The structure-activity relationship of this series of compounds is discussed, focusing on the length of the alkynyl side chain and bulkiness of the terminal cycloalkyl substituents in terms of binding activity and cardiovascular effects. All the 2-CAAs had a preferential affinity for A2 receptors. Of these derivatives, 2-(3-cyclopentyl-1-propyn-1-yl)adenosine (10b) exhibited the most selective affinity for A2 receptors (Ki ratio: A1/A2 = 70) on the basis of receptor binding. In the C-2 binding region of adenosine, compounds often have potent and/or selective A2 activity from introduction of an acetylenic group at the C-2 position followed by one methylene residue further followed by a hydrophobic substituent such as a cycloalkyl ring at the terminal position of the alkynyl side chain. Intravenous injection of 10b up to 100 micrograms/kg had a potent hypotensive effect without a marked decrease in heart rate in anesthetized SHR. Compounds 10j-s, with a hydroxyl group in the C-3" position of the alkynyl side chain, had a potent affinity for both A1 and A2 receptors, but they were not highly selective for A2 receptors. These compounds caused a marked bradycardia upon intravenous administration in anesthetized SHR. Oral administration of 10b (0.1-1 mg/kg) had a potent and long-lasting antihypertensive effect in conscious SHR.

A facile, alternative synthesis of 4'-thioarabinonucleosides and their biological activities.

4'-Thioarabinonucleosides, which are potential antiviral agents, were synthesized from D-glucose. 1,4-Anhydro-4-thioarabitol (8), which can be derived from diacetone glucose in nine steps, was subjected to Pummerer rearrangement after protection of the hydroxyl groups to give 1-O-acetyl-4-thioarabinose (11), which was condensed with nucleobases to give 4'-thioarabinonucleosides. The 5-substituted-4'-thioaraU (6a-e) derivatives showed anti-HSV-1 activity (ED50 = 0.43-3.50 micrograms/mL). 4'-ThioaraG (6h) and 2,6-diaminopurine 4'-thioarabinonucleoside (4'-thioaraDAP, 6g) showed antiviral activity against several herpes viruses and were particularly potent against human cytomegalovirus (0.010 and 0.022 microgram/mL, respectively).

Antitumor activity of a novel orally effective nucleoside, 1-(2-deoxy-2-fluoro-4-thio-beta-D-arabinofuranosyl)cytosine.

The antitumor activity of a novel 4'-thionucleoside, 1-(2-deoxy-2-fluoro-4-thio-beta-D-arabinofuranosyl)cytosine (4'-thio-FAC), was evaluated. 4'-Thio-FAC inhibited the in vitro growth of various human cancer cell lines, particularly the growth of cell lines established from gastric and colorectal carcinomas, while its oxy-type congener 1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)cytosine (FAC) showed little or no activity against such solid cancer cell lines. 4'-Thio-FAC showed a remarkable antitumor effect against human tumors subcutaneously implanted into nude mice and was highly effective even by oral administration. 4'-Thio-FAC was less susceptible to deamination by cytidine deaminase than FAC and 2'-deoxy-2',2'-difluorocytidine (gemcitabine) and therefore is a promising drug candidate for cancer chemotherapy.

Comparison of 1-(2-deoxy-2-fluoro-4-thio-beta-D-arabinofuranosyl)cytosine with gemcitabine in its antitumor activity.

The antitumor activity of a novel nucleoside, 1-(2-deoxy-2-fluoro-4-thio-beta-D arabinofuranosyl)cytosine (4'-thio-FAC) was compared with that of 2'-deoxy-2',2'-difluorocytidine (gemcitabine). 4'-Thio-FAC showed potent antitumor effects against various solid cancer cell lines in vitro. Also, gemcitabine showed remarkable in vitro antitumor effects, even more potent than 4'-thio-FAC. However, 4'-thio-FAC inhibited tumor growth more strongly than gemcitabine did at the same dose against human cancer cells implanted s.c. in nude mice. In addition, 4'-thio-FAC suppressed the tumor growth by oral administration. The toxicity of 4'-thio-FAC was weaker than that of gemcitabine in nude mice in both consecutive and intermittent administration. Accordingly, clinical usefulness of 4'-thio-FAC is expected.

Metabolism of 5'-ether prodrugs of 1-beta-D-arabinofuranosyl-E-5-(2-bromovinyl)uracil in rats.

1-beta-D-Arabinofuranosyl-E-5-(2-bromovinyl)uracil (BV-araU) is a selective antiherpesviral agent that has been shown to be metabolically stable in mice. However, E-5-(2-bromovinyl)uracil (BVU) is the major metabolite found after oral dosing in animals other than mice. When BV-araU was given orally to germ-free rats, only small amounts of BVU were found in the plasma, suggesting an important role of enterobacteria in the formation of BVU. Then, the metabolism of BV-araU prodrugs was studied in specific-pathogen free rats to select oral prodrugs of BV-araU with enhanced metabolic stability. 5'-O-Ethyl BV-araU (Et-BV-araU) gave about a 2-fold higher BV-araU blood concentration 3 and 6 hr after administration than after oral dosing of BV-araU, while the level of BVU was lower. Other aliphatic alkyl prodrugs also gave a lower level of BVU, but did not give the same elevation in blood concentration of BV-araU as did Et-BV-araU. Dosing of 5'-O-acetyl BV-araU resulted in blood concentrations of BV-araU and BVU similar to those after oral administration of BV-araU. 5'-O-Aromatic alkyl prodrugs showed poor bioavailability. A nearly 2-fold higher urinary recovery rate was seen for Et-BV-araU than for BV-araU or 5'-O-acetyl BV-araU. The conversion of Et-BV-araU to BV-araU was demonstrated in vitro using rat liver extract in the presence of co-factors, although the reaction was slow. The 5'-O-aliphatic alkyl prodrugs were completely resistant to degradation by enterobacteria, whereas the esters were partially degraded to BVU. Et-BV-araU may be a useful oral prodrug of BV-araU due to its increased metabolic stability and bioavailability.

Deglycosylation of antiherpesviral 5-substituted arabinosyluracil derivatives by rat liver extract and enterobacteria cells.

A number of antiherpesviral 5-substituted derivatives of 1-beta-D-arabinofuranosyluracil (araU) were significantly resistant to phosphorolysis by rat liver extract (S-9), but were gradually deglycosylated in a 2% enterobacteria cell suspension. The relative order of the resistance conferred by the different C-5 substituents was: 5-propynyl > 5-(E)-2-bromovinyl > 5-(E)-2-chlorovinyl > 5-methyl > 5-iodo. The 2'-fluoro derivatives of araU were completely resistant to phosphorolysis by both liver extract and enterobacteria, whereas the corresponding ribofuranosyl and 2'-deoxyribofuranosyl nucleosides were easily phosphorolysed by S-9, and were immediately cleaved in a 1% enterobacteria cell suspension. These findings suggest that antiherpesviral 5-substituted araU analogues can be relatively stable in vivo, when injected intravenously, and that degradation of 1-beta-D-arabinofuranosyl-5-(E-2-bromovinyl)uracil (sorivudine) following oral administration is due primarily to the action of enterobacteria.

mRNA expression of type I and type II receptors for activin, transforming growth factor-beta, and bone morphogenetic protein in the murine erythroleukemic cell line, F5-5.fl.

OBJECTIVE: Intracellular signaling of activin and transforming growth factor-beta (TGF-beta) is thought to be mediated by the same molecules (Smad2/3 and Smad4). Although differentiation of murine erythroleukemia F5-5.fl cells is induced by activin, it is not induced by TGF-beta, suggesting that at some point TGF-beta signaling is defective. The aim of this study was to investigate the unresponsiveness of F5-5.fl cells to TGF-beta. DESIGN: mRNA expression of ligands, receptors, and signal mediators for the TGF-beta family was examined in F5-5.fl cells using RT-PCR. RESULTS: Activin induced erythrodifferentiation of F5-5.fl cells in a dose-dependent manner. Neither TGF-beta1 nor bone morphogenetic protein (BMP)-4 affected the differentiation of F5-5.fl cells in the presence or absence of activin. Although mRNAs of TGF-betas (TGF-beta1, TGF-beta2 and TGF-beta3) were detected, those of inhibin/activin (alpha-, betaA- and betaB-subunits) and BMPs (BMP-2, BMP-4 and BMP-7) could not be detected in the cells, suggesting that neither activins nor BMPs are produced in F5-5.fl cells. The expression of both type I (ALK-4/ActRIB) and type II (ActRII) receptors for activin was detected in F5-5.fl cells. In contrast, while the expression of type I receptor for TGF-beta (ALK-5/TbetaRI) was detected, that of type II receptor (TbetaRII) was not. The mRNA of all Smads examined was detected in F5-5.fl cells. CONCLUSIONS: A defect in the type II receptor might cause unresponsiveness to TGF-beta in F5-5.fl cells. An erythrodifferentiation assay using F5-5.fl cells would be useful for measuring net activin activity because it would not be necessary to consider endogenous activins and BMPs.

Effects of inline filtration on delivery of gentamicin at various flow rates.

The effects of inline filtration on delivery of gentamicin (GM) in the pediatric field were studied. The filter sets (Pall 0.20 micron. JMS 0.20 micron, and IVEX 2.022 micron) were studied using a simulated system. 10 mg of GM was injected into the system containing 5% dextrose in water (flow rate: 50 ml/hr, 10 ml/hr and 2 ml/hr) with horizontal and vertical settings of the inline filters. In case of 50 ml/hr, delivery of GM of Pall showed nearly the same delivery pattern as compared with no filter setting. However, JMS and IVEX 2 showed little differences. In case of 10 ml/hr and 2 ml/hr those differences became more significant. Delivery of GM was influenced by the priming volume of the filters, increasingly so at slow flow rates. Filter settings also influenced the delivery of GM. Furthermore, with regards to the results of the Vitamin K2 delivery and the technetium radiotracer method, JMS and IVEX 2 filters were observed to have some stagnation of drugs in the filter. Not only priming volumes of the filters affect delivery of drugs, filter designs also have an influence. The use of the inline filters is important in the pediatric field, but their charactaristics for drug delivery pattern should be considered.

A morphologic study of Carpentier-Edwards pericardial xenografts in the mitral position exhibiting primary tissue failure in adults in comparison with Ionescu-Shiley pericardial xenografts.

OBJECTIVE: We sought to investigate the durability and mechanism of the Carpentier-Edwards pericardial xenograft in the mitral position in comparison with that of the Ionescu-Shiley pericardial xenograft. METHODS: A total of 284 patients who received the Ionescu-Shiley pericardial xenograft in the mitral position between 1980 and 1984 and 84 patients who received the Carpentier-Edwards pericardial xenograft in the mitral position between 1984 and 1999 were included in the study. The freedom from reoperation rates for both graft types were determined. For morphologic study, the pathologic findings of 23 valves of 123 explanted Ionescu-Shiley pericardial xenografts with structural valve deterioration, nonstructural valve deterioration, or both were determined and compared with those of 20 explanted Carpentier-Edwards pericardial xenografts with structural valve deterioration, nonstructural valve deterioration, or both. Each pathologic finding was graded and assigned a score. Both types were matched for age at reoperation (50-75 years) and duration of valve function (8-11 years). RESULTS: Freedom from reoperation caused by structural valve deterioration, nonstructural valve deterioration, or both was significantly better for Carpentier-Edwards pericardial xenografts than for Ionescu-Shiley pericardial xenografts at 8 years after the operation (Carpentier-Edwards pericardial xenografts: 91.3% vs Ionescu-Shiley pericardial xenografts: 71.9%, P =.0061), but it was similar for both types at 12 years (Carpentier-Edwards pericardial xenografts: 43.6% vs Ionescu-Shiley pericardial xenografts: 43.6%, P =.2865). No severe leaflet tears were seen among Carpentier-Edwards pericardial xenografts. The mean area percentage of tissue overgrowth was 15.3% in Carpentier-Edwards pericardial xenografts and 3.4% in Ionescu-Shiley pericardial xenografts (P =.0001). The mean calcification area percentage was 13.6% in Carpentier-Edwards pericardial xenografts and 31.5% in Ionescu-Shiley pericardial xenografts (P =.0001). CONCLUSIONS: Tissue overgrowth on the atrial surface, ventricular surface, or both was the cause of structural valve deterioration, nonstructural valve deterioration, or both of Carpentier-Edwards pericardial xenografts in adults. This was different from Ionescu-Shiley pericardial xenograft failure, which resulted from severe calcification and leaflet tears. Organized thrombi on cusps, in addition to valve design, may have contributed to such tissue overgrowth on Carpentier-Edwards pericardial xenografts.

In vitro and in vivo antiviral activity of 1-beta-D-arabinofuranosyl-E-5-(2-bromovinyl)uracil (BV-araU) and related compounds.

BV-araU and related compounds such as CV-araU, IV-araU and BV-araUMP showed marked activity against herpes simplex virus type 1 (HSV-1) in human embryonic lung fibroblast cells. BV-araU, CV-araU and BV-araUMP were also effective in mice infected intracerebrally with HSV-1. Especially, when mice were infected with a low dose of virus, both intravenous and oral treatment with BV-araU proved capable of increasing the mean survival time and decreasing the final mortality of the infected mice. The in vivo anti-HSV-1 activity of BV-araU was comparable to that of BVDU. BV-araU exhibited little toxicity for mice.