A Kunjin replicon vector encoding granulocyte macrophage colony-stimulating factor for intra-tumoral gene therapy.

We have recently developed a non-cytopathic RNA replicon-based viral vector system based on the flavivirus Kunjin. Here, we illustrate the utility of the Kunjin replicon system for gene therapy. Intra-tumoral injections of Kunjin replicon virus-like particles encoding granulocyte colony-stimulating factor were able to cure >50% of established subcutaneous CT26 colon carcinoma and B16-OVA melanomas. Regression of CT26 tumours correlated with the induction of anti-cancer CD8 T cells, and treatment of subcutaneous CT26 tumours also resulted in the regression of CT26 lung metastases. Only a few immune-based strategies are able to cure these aggressive tumours once they are of a reasonable size, illustrating the potential of this vector system for intra-tumoral gene therapy applications.

An equine herpesvirus 1 (EHV1) abortion storm at a riding school.

An outbreak of EHV1 abortions occurred at a riding school in The Netherlands in 1991. Seven of twelve pregnant mares aborted, and another foal died at 8 days of age. Six abortions occurred within 12 days in March after an initial abortion on 8 February. Four mares delivered live foals. Virological examination of four aborted foals revealed an EHV1 infection. Serological results for paired sera from 17 horses suggested, that the initial abortion on 8 February was the index case, and probably caused the other six abortions. The index case could well have been caused by reactivation of latent virus induced by transport stress. The laboratory results are discussed in the light of the present knowledge of the pathogenesis and epidemiology of EHV1 abortion.

[The incidence of multiple ovulations in Dutch warmblood mares]. / De incidentie van dubbele ovulaties bij het Nederlands warmbloedpaard.

In the period 1994-1996 1030 oestruses of Dutch Warmblood mares were evaluated on the incidence of multiple ovulations diagnosed by rectal palpation. Ultrasonography was not used. All follicles > 25 mm were noted. The examination was repeated every 48 hours. The incidence of multiple follicle development was 7.3%. In a group of 50 ultrasonographically diagnosed twin-pregnant mares only 14 (28%) had been detected by rectal palpation as a multiple ovulation. This suggests an incidence of multiple ovulations in Dutch Warmblood mares of 7.3 x 1/28 x 100 = 26%. Restrictions of rectal palpation are discussed. Ultrasonography is essential for the diagnosis of multiple ovulations. The importance of a good twin-prevention programme is emphasized.

[Spontaneous and manual embryo reduction in mares: a twin prevention programme]. / Natuurlijke versus manuele embryoreductie van tweelingdracht bij de merrie resulterend in een tweeling preventie programma.

Data from the literature and own data for 67 twin pregnancies were used to establish the factors essential to the decision on how to treat twins at different gestational ages. Spontaneous (natural) reduction was compared with manual embryo reduction. Manual embryo reduction is always indicated when a twin is diagnosed before day 16 after ovulation. Thereafter, the type of fixation is the main determinant. Manual embryo reduction is always first choice for bilateral and unilateral non adjacent embryos and must be applied as early as possible. The change of natural reduction up to day 30, is higher for unilateral adjacent twins than is the chance of success after manual reduction. From day 30 onwards manual embryo reduction is preferable. The results are summarized in a twin prevention programme which describes how twin pregnancies can be avoided after the development of endometrial cups.

[Rectal tears in the horse: malpractice or an unfortunate accident?]. / Rectumscheuren bij het paard: beroepsfout ofeen ongelukkig toeval?

Rectal tears are a relatively rare complication of rectal palpation, mating or dystocia, and idiopathic spontaneous occurrence of rectal perforation has also been described. Rectal tears have been classified in a three or a four-grade system. Immediate recognition of the fact that a tear has been made and prompt action will improve the horses chance of survival, and is the best defence of the veterinarian against legislation. There is no clear explanation why rectal tears sometimes occur. A questionnaire of the Netherlands Equine Veterinary Association revealed that rectal tears occurred both to inexperienced veterinarians and to very experienced colleagues, working with or without a probe for ultrasonography. In the opinion of the authors, the approach in the legislation of rectal tears should be that a rectal tear is only considered 'malpractice' if the veterinarian obviously acted carelessly. However, this would create the ridiculous situation that it seems better for the veterinarian-client relationship when the veterinarian confesses to 'careless' rectal palpation. This point needs further clarification, and perhaps an 'insurance of the horse for rectal palpation' will be the solution. Further, retrospectively over the last ten years, the problem is often not 'making a rectal tear', but 'lacking recognition of making a tear'. Whenever a rectal tear is suspected, the veterinarian must assess its severity, discuss the problem openly with the owner and apply appropriate treatment including referral.