Pars plana vitrectomy with PFO-silicone oil exchange and endolaser retinopexy for treatment of RD in dogs is highly successful and associated with overall good visual outcome.

This study investigates the role of tumor nitric oxide (NO) and vascular regulation in tumor ulceration following high-dose tumor necrosis factor-a (TNF) treatment. Using TNF-responsive (MethA) and nonresponsive (LL2) mouse tumors, tumor NO concentration was measured with an electrochemical sensor and tumor blood flow by Doppler ultrasound. Mice were also pretreated with a selective inducible nitric oxide synthase (iNOS) inhibitor, 1400 W. Tumors harvested from TNF-treated mice were cryosectioned and immunostained for murine macrophages, or/and iNOS. MethA tumor-bearing mice were depleted of macrophages. Pre-and post-TNF tumor NO levels were measured continuously, and mice were followed for gross tumor response. In MethA tumors, TNF caused a 96% response rate, and tumor NO concentration doubled. Tumor blood flow decreased to 3% of baseline by 4 hr and was sustained at 24 hr and 10 days post-TNF. Selective NO inhibition with 1400 W blocked NO rise and decreased response rate to 38%. MethA tumors showed tumor infiltration by macrophages post-TNF and the pattern of macrophage immunostaining overlapped with iNOS immunostaining. Depletion of macrophages inhibited tumor NO increase and response to TNF. LL2 tumors had a 0% response rate to TNF and exhibited no change in NO concentration. Blood flow decreased to 2% of baseline by 4 hr, recovered to 56% by 24 hr and increased to 232% by 10 days. LL2 tumors showed no infiltration by macrophages post-TNF. We conclude that TNF causes tumor infiltrating, macrophage-derived iNOS-mediated tumor NO rise and sustained tumor blood flow shutdown, resulting in tumor ulceration in the responsive tumor. ' 2008 Wiley-Liss, Inc.Key words: high-dose TNF; nitric oxide; blood flow; macrophage; tumor The therapeutic potential of targeting the tumor vascular supply is now widely recognized and has led to improvement in survival in patients with advanced cancer. 1-3 Continued investigation into novel strategies of antivascular therapies and further study of the mechanisms of current antivascular therapies will help to advance this field.Regional perfusion with high-dose recombinant human tumor necrosis factor-a (TNF) is an effective antivascular therapy in clinical practice. It achieves an overall response rate of 90-100% and complete response rate of 80-90% when combined with melphalan for extremity melanoma, making this treatment one of the most effective single-administration therapies for solid malignancies. 4-6 TNF in combination with melphalan has demonstrated synergistic antitumor activity in the treatment of melanomas and soft tissue sarcomas that are recurrent, deep-seated or bulky. One of the advantages of this therapeutic is that it is selective to tumor tissue and spares surrounding normal tissue. 7 Despite the tumoricidal potential of TNF, severe toxicity such as hypotension, abnormalities in liver function, leukopenia and thrombus formation has made TNF difficult to be used systemically as an antitumor drug. This problem has been circumvented by using isolated limb perfusion (I...

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A 1-year-old, intact female, domestic shorthaired cat was presented for dysuria resulting from perineal scarring subsequent to injuries incurred during a cat fight. A prepubic urethrostomy was performed to manage the dysuria. Eleven months later, the cat was re-presented with a 3-day history of pyrexia and inappetence. A pinpoint opening extending 0.5 cm ventral to the anus on midline, exuding a clear discharge, was noted in the perineal region. A contrast fistulogram was performed, and a vaginoperineal fistula was diagnosed. The fistulous tract was a result of vulvar stricture from the trauma of the cat fight. A vaginoplasty was performed to create an opening for vaginal secretions. This is the first published report of a prepubic urethrostomy performed in a female cat.

During gastrulation in amphibians, secreted factors from Spemann's organizer act on dorsal ectoderm to induce the central nervous system. A number of secreted factors produced by Spemann's organizer have recently been identified. The TGFbeta family member Xnr3 is similar in amino acid sequence to the mouse factor nodal and is expressed in a restricted group of cells in the superficial layer of Spemann's organizer. Xnr3, unlike the related factors nodal, Xnr1 and Xnr2, lacks mesoderm-inducing activity. We report here that Xnr3 can directly induce neural tissue in Xenopus ectoderm explants (animal caps). Injection of animal caps with either Xnr3 RNA or plasmids induces the expression of the pan-neural genes NCAM and nrp1, as well as the anterior neural marker Cpl1. A growing body of evidence suggests that neural induction in Xenopus proceeds as the default in the absence of epidermis inducers. The best candidates for the endogenous epidermis inducers are BMP-4 and BMP-7. The neural inducing activity of Xnr3 can be inhibited by overexpression of BMP-4, as has been observed with the neural inducers noggin, chordin and follistatin. Furthermore, Xnr3 can block mesoderm induction by BMP-4 and activin, but not by Xnr2. The structural basis underlying the divergent activities of Xnr2 and Xnr3 was analyzed using site-directed mutagenesis. Mutations introduced to the conserved cysteine residues characteristic of the TGFbeta family were found to inactivate Xnr2, but not Xnr3. The most unique feature of Xnr3 is the absence of a conserved cysteine at the C terminus of the protein. This feature distinguishes Xnr3 from other TGFbeta family members, including Xnr2. However, we observed that changing the C terminus of Xnr3 to more closely resemble other TGFbeta family members did not significantly alter its activity, suggesting that other structural features of Xnr3 distinguish its biological activity from Xnr2.