Stratification, blinding and placebo effect in a randomized, double blind placebo-controlled clinical trial of gold bead implantation in dogs with hip dysplasia

The purpose of this study was to investigate the need for and choice of stratification factors, and the effects of blinding and placebo in a clinical experiment. Eighty dogs with canine hip dysplasia (CHD) were included in a randomized, placebo-controlled and double blind clinical trial with stratified parallel group design, in which body weight and degree of CHD were used as stratification factors. Thirty-eight dogs were allocated to gold bead implantation and 42 to placebo. After six months, 33 of the 42 placebo-treated dogs received gold bead implantation in an open study lasting a further 18 months. The main outcome variable in the study was change in pain signs of CHD as assessed by the owner. No significant difference in the main outcome variable, regardless of the treatment given, could be detected in the two chosen stratification factors. The only factor to influence the main outcome variable significantly was age. The blinding procedure used in the study, in which 60% of the owners correctly guessed the treatment given, was found sufficient. Of those who guessed the treatment erroneously, 88% believed the treatment given was gold bead implantation. The treatment efficacy after six months in the blinded treatment group was found to be significantly larger compared to the efficacy obtained in the open study. A significant placebo effect was therefore detected. CONCLUSION AND CLINICAL RELEVANCE: The age of the dogs influenced the outcome of the CHD treatment, and is recommended as a stratification factor. A significant placebo effect has to be expected and an optimal blinding procedure is necessary in similar clinical studies.     

Vasopressin secretion in response to osmotic stimulation and effects of desmopressin on urinary concentrating capacity in dogs with pyometra

OBJECTIVE: To determine vasopressin (VP) secretory capacity during osmotic stimulation and the response to desmopressin treatment in dogs with pyometra and control dogs. ANIMALS: 6 dogs with pyometra before and after ovariohysterectomy and 6 control dogs. PROCEDURE: Urine osmolality (Uosm) was measured during 12 hours. Values measured on the first day defined the basal Uosm pattern. On the second day, dogs were given desmopressin to induce a desmopressin-stimulated Uosm pattern. On day 3, the VP response to osmotic stimulation was examined. RESULTS: Median Uosm on day 1 was 340 mOsm/kg (range, 104 to 1,273 mOsm/kg) and 807 mOsm/kg (range, 362 to 1,688 mOsm/kg) in dogs with pyometra before and after surgery, respectively, and 1,511 mOsm/kg (range, 830 to 1,674 mOsm/kg) in control dogs. Median Uosm during desmopressin treatment was 431 mOsm/kg (range, 168 to 1,491 mOsm/kg) and 1,051 mOsm/kg (range, 489 to 1,051 mOsm/kg) in dogs with pyometra before and after surgery, respectively, and 1,563 mOsm/kg (range, 1,390 to 2,351) in control dogs. In dogs with pyometra, threshold for VP secretion was lower before surgery (median, 340 mOsm/kg; range, 331 to 366 mOsm/kg) than after surgery (median, 358 mOsm/kg; range, 343 to 439 mOsm/kg) or in control dogs (median, 347 mOsm/kg; range, 334 to 360 mOsm/kg). Highest maximum plasma VP values were found in dogs with pyometra. CONCLUSIONS AND CLINICAL RELEVANCE: Dogs with pyometra had increased urine concentration in response to desmopressin but not to the degree of control dogs, whereas VP secretory ability was not reduced.     

Optimum Dietary Level of L-ascorbic Acid for Japanese Eel, Anguilla japonica

A feeding experiment was conducted to determine the optimum dietary level of ascorbic acid (AsA) for Japanese eel juveniles using L-ascorbic acid Ca based on growth, AsA content in tissues, hematology, and bactericidal activity of serum with Escherichia coli . Test diets with six levels of AsA (3, 10, 27,126, 645, and 3,135-mg/kg diet) as Ca ascorbate were fed to juvenile Japanese eels (11.0 ± 0.2 g) once a day for 8 wk. High survival rates (> 80%) were observed among all dietary treatment groups. The specific growth rates of the fish fed diets containing 3 and 10-mg AsA/kg were significantly (P < 0.05) lower than those of other groups. Liver and brain AsA contents of the fish fed diets containing 3, 10, and 27-mg AsA/kg were significantly (P < 0.05) lower than those of the fish fed diets containing 645 and 3,135-mg AsA/kg. Hemoglobin content tended to be higher in the fish fed diets containing 645 and 3,135-mg AsA/kg than those of the fish fed other diets. Hematocrit value and total serum protein content of the fish fed diets containing 645 and 3135 mg AsA/kg were significantly (P < 0.05) higher than those of the other groups. The fish fed diets containing more than 27-mg AsAlkg showed a higher bactericidal activity of serum than the fish fed the diets containing 3-mg and 10-mg AsA/kg. The optimum dietary level of AsA for the Japanese eel juveniles growth was estimated to be more than 27-mg AsA/kg. Furthermore, the inclusion of 645-mg AsA/kg or more also increased the hematocrit, hemoglobin, total serum protein value, and liver and brain vitamin C concentrations.     

Evaluation of Liposomal Radiochemotherapy for Treatment of Cancer

Introduction: Pegylated liposomes target solid tumors by exploiting the capillary leakage properties of tumor neovasculature. The goal of the study was to investigate distribution and tumor targeting properties of the alpha‐particle emitter ²²³Ra, encapsulated in doxorubicin‐containing‐liposomes (Caelyx^®/Doxil^®). Methods: Caelyx^® was given before the injection of liposomal ²²³Ra to reduce the reticulo‐endothelial‐system uptake. A pilot study was conducted to determine the optimal time interval between the pre‐treatment/treatment. Subsequently a more extensive distribution study was performed in normal BalbC mice. In addition, distribution and tumor uptake was evaluated in a human osteosarcoma xenograft mice model and in a dog with spontaneous osteosarcoma. Results: Optimal blood‐to‐liver and blood‐to‐spleen ratios of liposomal radium was achieved in animals that received pre‐treatment with Caelyx^® 4 days in advance. Blood clearance was relatively slow, in mice t_1/2 was ～28 h (BalbC mice) and in the dog t_1/2 was ～ 39 h. In mice the liver uptake appeared to be relatively low in contrast to the spleen, where there was a significant uptake. In the dog the uptake in both liver and spleen was moderate. In the xenograft model there was generally a higher retention of activity in the tumor vs. soft tissue. In the dog the 24 h uptake was considerably higher in both calcified and non‐calcified tumor metastases of different organs, than in normal tissue. Conclusions: Liposomal ²²³Ra has a relevant biodistribution and blood clearance for tumor targeting. More extensive future studies are supported by the favourable tumor/normal‐tissue ratio in a dog with spontaneous osteosarcoma.     

Caprine mycoplasmosis: an outbreak of mastitis and arthritis requiring the destruction of 700 goats

An acute outbreak of mastitis and arthritis in a herd of 700 goats required the destruction of all but the few animals that were held for observation. The milk of nearly all of about 400 lactating does contained almost pure cultures of Mycoplasma putrefaciens with counts in 150 samples up to 1 X 10(9) colony forming units/ml. At post mortem examination the joints of both the adults and kids contained a fibrinopurulent discharge. M putrefaciens was isolated in pure cultures and large numbers from joints, tissues and fluid not previously known to harbour this mycoplasma: brain, kidneys, lungs, lymph nodes, uterus and urine. The outbreak was milkborne and initiated by infusion of the pathogen into the teat canal by poor hygiene in the milking parlour and by feeding raw colostrum to kids. All but 12 of the herd of 700 goats were killed or sold for slaughter.     

Expression of 3beta-hydroxysteroid dehydrogenase, cytochrome P450-c17, and sulfotransferase 2B1 proteins in liver and testis of pigs of two breeds: relationship with adipose tissue androstenone concentration

An excessive accumulation of androstenone in pig adipose tissue is a major contributor to the phenomenon of boar taint. Androstenone deposition is dependent on the rate of androstenone biosynthesis in testis and androstenone degradation in liver. The aim of the current study was to examine the possibility of the existence of breed-specific mechanisms controlling androstenone accumulation in pig adipose tissue. The specific objective was to investigate the expression of some of the key enzymes involved in testicular and hepatic androstenone metabolism in pigs of 2 breeds by using animals with high and low androstenone concentrations within each breed. The study was conducted with Norwegian Landrace (N. Landrace) and Duroc boars. The mean androstenone values for the low- and high-androstenone groups were 0.1 +/- 0.01 microg/g and 7.58 +/- 0.68 microg/g for N. Landrace boars, and 0.22 +/- 0.04 microg/g and 13.55 +/- 1.14 microg/g for Duroc boars. The enzymes investigated were 3beta-hydroxysteroid dehydrogenase (3beta-HSD), cytochrome P450-c17, and sulfotransferase 2B1 (SULT2B1). Expression of cytochrome P450-c17 in liver and testis did not differ between animals with high and low androstenone concentrations in either the N. Landrace or Duroc breed. Expression of hepatic 3beta-HSD, which catalyzes the first stage of androstenone degradation, was decreased in high-androstenone N. Landrace boars (P < 0.01), but not in high-androstenone Duroc boars. In contrast, the expression of hepatic SULT2B1, which catalyzes the second stage of steroid catabolism, was decreased in high-androstenone Duroc animals (P < 0.05), but not in high-androstenone N. Landrace animals. Sulfotransferase 2B1 was also inhibited in testis of high-androstenone pigs of both breeds compared with low-androstenone animals. We report breed differences in expression of the androstenone-metabolizing enzymes 3beta-HSD and SULT2B1 in the liver of high- and low-androstenone pigs. It is suggested that accumulation of androstenone in adipose tissue of N. Landrace boars might be related to a low rate of hepatic androstenone degradation in metabolic stage I, whereas the high androstenone concentration in Duroc boars might be related to a low rate of androstenone metabolism in metabolic stage II.     

Resistance of aquaculture net cage materials to biting by Atlantic Cod (Gadus morhua)

Cod bite on aquaculture net cages has resulted in damages like frayed netting and holes, which in part can explain why cultured cod have escaped more frequently than salmon over the last years. We describe damages found on various netting materials subjected to cod bite through field experiments at commercial cod farms. Further, a method to test local cod bite resistance of traditional netting structures is suggested and initial results from a test jig prototype are given. Results from field experiments indicated that cod may have been attracted by types of netting that made it possible to draw filaments out of the twine, while stiff, coated netting structures and thick filaments showed no sign of bite damage during the test period. We concluded that netting materials for cod aquaculture must be resistant to cod bite or be repellent or uninteresting for cod. Based on the present findings, the better choice among the traditional netting materials seemed to be hard-laid netting materials, preferably with a primer that glues the filaments together.