Reinforcement of the suture line with an ePTFE graft attached with histoacryl glue in duodenal trauma.

BACKGROUND: Most duodenal injuries are managed with primary repair, but the degree of duodenal-wall injury may threaten the integrity of the primary repair. Therefore, we evaluated whether the primary repair site could be reinforced with histoacryl glue (HAG) or HAG with an expanded polytetrafluoroethylene (ePTFE) mesh. METHODS: Grade 3 duodenal injury in the second portion of the rat duodenum was chosen as a standard trauma model. Thirty-three male rats were divided into sham (n = 3), 2-layer primary repair (n = 10), 1-layer primary repair plus HAG application (n = 10) and ePTFE attached with HAG over the 1-layer primary repair site (n = 10) groups. Ten-day survival, adhesion grades and histological assessment were taken as outcome measures. RESULTS: A significant survival advantage was identified in the group that had an ePTFE graft attached with HAG over a 1-layer repair when compared with the group that had a 2-layer primary repair. Adhesion grades were found to be particularly increased in the group that had an ePTFE graft attached with HAG over the primary repair site, moderately increased in the primary repair plus HAG application group and lower in the 2-layer primary repair group. ePTFE graft application was found to be beneficial to coverage of the HAG-dependent empty spaces in the serosal layer. CONCLUSIONS: A primary repair site after duodenal trauma or a difficult duodenal stump can be reinforced with the application of HAG or ePTFE graft implantation with HAG.     

Pattern electroretinography and visual evoked potentials in optic nerve diseases.

BACKGROUND: To evaluate transient pattern electroretinography (PERG) and pattern visual evoked potential (VEP) for the diagnosis, differential diagnosis and follow-up of optic nerve diseases. METHODS: Twenty-nine consecutive patients (14 female, 15 male) with the diagnosis of ischaemic optic neuropathy (n=14) and optic neuritis (n=15) were included in this study. Mean age of the patients with ischaemic optic neuropathy was 63.3+/-3.3 (60-78) years and the mean age of the patients with optic neuritis was 28.3+/-8.4 (19-43) years. In each patient ophthalmological examination and systemic evaluation were done and VEP and PERG were recorded. As a control group, VEP recordings of 35 healthy subjects were included. RESULTS: In the ischaemic optic neuropathy group (group 1), mean VEP amplitude (+/-SD) (1.96+/-0.95 microV) was found to be decreased significantly in the affected eyes in comparison to the control group and the unaffected eyes. The delay in latency (116.3+/-20.14 msec in the affected eyes compared with 101.31+/-6.19 msec in unaffected eyes) was statistically significant when compared with the healthy subjects. In the optic neuritis group (group 2), VEP amplitude was decreased (4.13+/-4.04 microV vs 6.97+/-3.35 microV and 6.97+/-4.43 microV) and latency was increased (122.59+/-20.09 msec vs 101.31+/-6.19 msec and 108.76+/-13.57 msec) in affected eyes significantly in comparison to the unaffected eyes and control group, respectively. Even though there were no significant differences for P50 latency and N95/P50 ratios between affected and unaffected eyes in both groups, N95 amplitude decreased significantly in the affected eyes of the ischaemic optic neuropathy patients and N95 latency was found to be decreased in optic neuritis patients. There was no correlation between VEP and PERG findings in both groups. CONCLUSION: VEP amplitude decreased significantly in ischaemic optic neuropathies while latency delay was more significant in patients with optic neuritis. PERG findings showed decreased N95 amplitude in ischemic optic neuropathy without associated latency changes.     

Pharmacokinetics of fluorinated 2-nitroimidazole hypoxic cell radiosensitizers in murine peripheral nervous tissue.

We have previously reported that KU-2285, a 2-nitroimidazole with a fluorinated N1-substituent (-CH2-CF2CONH(CH2)nOH, n = 2), was a promising hypoxic cell radiosensitizer. In this study the pharmacokinetics of KU-2285 and its related compounds (n = 3 and n = 4) were compared with those of etanidazole (a 2-nitroimidazole with an N1-substituent of -CH2CONH(CH2)nOH, n = 2) and its related compounds (n = 3 and n = 4) to assess the effects of incorporation of a CF2 group. The lipophilicity of the fluorinated compounds was higher than that of etanidazole, as measured by the octanol/water partition coefficient. As the number of CH2 groups increased, the lipophilicity of the compounds in both the KU-2285 and etanidazole series increased. The brain tissue levels of the fluorinated compounds were as low as those of the etanidazole derivatives, while the biological half-lives of the fluorinated compounds in peripheral nervous tissues were shorter than those of related non-fluorinated compounds.     

A novel compound heterozygous dysferlin mutation in Miyoshi myopathy siblings responding to dantrolene

Miyoshi myopathy (MM) is an autosomal recessive distal muscular dystrophy characterized by mutations of the dysferlin gene. Although several pairs of homozygous/heterozygous mutations have been reported, few effective treatments of MM are available. We had observed the decreased serum creatine kinase (CK) before and after administration of dantrolene in the elder brother and the increased serum CK before and after discontinuance of the drug on suspicion of drug-induced hepatopathy in the younger sister. We report a novel pair of heterozygous mutations in the 3'-splicing site of exon 26 and the translation site of exon 28 of the dysferlin gene in two siblings, and effective treatment of their MM with dantrolene.     

Biochemical Modulation of 5-Fluorouracil with Murine Interferon-α/β Against Murine Renal Cell Carcinoma

Department of Urology, School of Medicine, Keio University, Tokyo, Japan
Background Conventional therapy for renal cell carcinoma using interferon (IFN) has shown limited antitumor action. The purpose of our study was to investigate synergistic antitumor effects of IFN and 5-fluorouracil (5-FU), and to elucidate the mechanisms of interaction between the 2 agents in mice.
Methods Antitumor effects and biochemical modulation of murine IFN-α/β and 5-FU were determined against the murine renal cell carcinoma cell line, Renca, in vivo. The activity of thymidylate synthetase and thymidine kinase was measured using cytosolic extracts of the tumors.
Results Combination treatment with IFN-α/β and 5-FU produced a significant enhancement of growth inhibition against Renca tumor. Treatment with 5-FU resulted in a 2.7-fold increase in the total amount of thymidylate synthetase and an 11.6-fold increase in the thymidylate synthetase inhibition rate, while the administration of IFN-α/β did not significantly reduce the 5-FU-induced increase in thymidylate synthetase. The administration of IFN-α/β decreased thymidine kinase activity to 65.5% maximally, compared with that in the control mice or the mice treated with 5-FU.
Conclusions The reduction of thymidine kinase caused by treating the mice with IFN-α/β changes the utilization of exogenous thymidine for DNA synthesis, and may represent the mechanism of the additive antitumor effect of the 2 agents, through the suppression of the salvage pathway for deoxythymidine monophosphate induction.     

The course ofAngiostrongylus cantonensis infection in athymic nude and neonatally thymectomized mice

BALB/c athymic nude and thymus-reconstituted nude mice and neonatally thymectomized BALB/c mice were infected with stage 3 larvae ofAngiostrongylus cantonensis and the worm burdens of the mice were determined at various times after infection. When the nude and thymectomized mice were exposed to the parasite, some worms were found to migrate from the brain to lungs but died there without reaching maturity. This pulmonary arterial migration of the worms in the nude mice did not occur following thymic reconstitution. These data suggest that the inability of murine intracranial worms to migrate to the lungs is at least in part due to thymus-dependent mechanisms, and also that the failure of worm maturation in mouse lungs might be due to thymus-independent immune mechanisms and/or nonimmunological mechanisms.     

Two-week, but not 1-week, hypoxic exposure enhances nitric oxide-mediated basal tone regulation in rat resistance pulmonary arteries

We measured internal diameter (ID) changes in resistance and conduit pulmonary arteries of 1- and 2-week hypoxic rats and normoxic control rats in response to nitric oxide synthase (NOS) inhibitors in vivo. At 2 weeks of hypoxic exposure, the ID reduction as a result of NOS inhibition was enhanced within the resistance arteries, but not at 1 week of hypoxia.     

PCR based mutation screening of the laminin alpha2 chain gene (LAMA2): application to prenatal diagnosis and search for founder effects in congenital muscular dystrophy.

Classical congenital muscular dystrophy with merosin deficiency is caused by mutations in the laminin alpha2 chain gene (LAMA2). Extended sequencing of the introns flanking the 64 LAMA2 exons was carried out and, based on these sequences, oligonucleotide primers were designed to amplify the coding region of each exon separately. By PCR-SSCP analysis, we identified eight new mutations in nine families originating from various countries. All induced a premature truncation of the protein, either in the short arm or in the globular C-terminal domain. A 2 bp deletion in exon 13, 2098delAG, was found in three French non-consanguineous families and a nonsense mutation of exon 20, Cys967stop, in two other non-consanguineous families originating from Italy. Determination of rare intragenic polymorphisms permitted us to show evidence of founder effects for these two mutations suggesting a remote degree of consanguinity between the families. Other, more frequent polymorphisms, G to A 1905 (exon 12), A to G 2848 (exon 19), A to G 5551 (exon 37), and G to A 6286 (exon 42), were used as intragenic markers for prenatal diagnosis. This study provides valuable methods for determining the molecular defects in LAMA2 causing merosin deficient congenital muscular dystrophy.