Comparisons of different combinations of analogues of PGF2 alpha and dopamine agonists for the termination of pregnancy in dogs.

Groups of five pregnant bitches were treated to terminate the pregnancy with four combinations of drugs, starting 28 days after the estimated surge of luteinising hormone (LH), 22 to 28 days after the first mating. The treatments were: cabergoline administered orally for 10 days at a dose of 5 micrograms/kg and a single subcutaneous injection of 2.5 micrograms/kg cloprostenol at the start of the treatment; the same dose of cabergoline plus two doses of 1 microgram/kg cloprostenol administered on days 28 and 32 after the LH surge; bromocryptine administered orally at a dose of 30 micrograms/kg three times a day for 10 days plus a single dose of 2.5 micrograms/kg cloprostenol; the same dose of bromocryptine plus two doses of 1 microgram/kg cloprostenol; and a group of five pregnant bitches was left untreated. The pregnancies were terminated in all but one of the treated bitches, in each case by resorption of the fetuses. There were few side effects in the bitches treated with two doses of 1 microgram/kg cloprostenol, and were present but acceptable in those treated with one dose of 2.5 micrograms/kg. Plasma progesterone concentrations decreased to less than 1 ng/ml within 72 hours of the start of treatment and remained low except in the bitch in which pregnancy was not terminated. In the five untreated bitches, plasma progesterone remained high and they whelped normally. In the treated groups, the intervals between successive displays of oestrus were reduced by approximately 70 days in comparison with previous cycles or with the control group, but the fertility of the dogs was not affected adversely.     

Efficacy, tolerance and acceptability of Incontex in spayed bitches with urinary incontinence

A clinical study about efficacy and acceptance of Incontex in spayed bitches with urinary incontinence was performed. In a randomised, double-blinded study the efficacy and acceptance of Incontex (Dr. E. Gr?ub AG, Bern, Schweiz) in bitches with urethral sphincter incompetence due to spaying was evaluated under field conditions. The active ingredient of the Incontex Syrup is phenylpropanolamine (PPA), an alpha1-adrenergic agonist. The study was performed using 24 spayed, incontinent bitches. Over a first period of treatment of 30 days the bitches received either Incontex, at 1.5 mg/kg twice per day, or a placebo. In the second period of 30 days all 24 bitches were treated with Incontex at the recommended dose. Any changes in the incontinence compared with the situation before the study were evaluated. RESULTS: Of 24 bitches 21 (88%) became continent and in 2 bitches (8%) urinary incontinence improved. In only 1 bitch (4%) the medication did have no effect. Five bitches (21%) showed side effects. The acceptance of Incontex was good. CONCLUSION AND CLINICAL RELEVANCE: Incontex can be recommended as an efficient and well-tolerated medication for the treatment of bitches with urinary incontinence after spaying. The oral application of 1.5mg/kg BW phenylpropanolamine twice daily has been approved.     

Efficacy and dosage titration study of mibolerone for treatment of pseudopregnancy in the bitch

A controlled, blind-labeled, dose-response field trial was conducted to evaluate the efficacy of mibolerone as a treatment for pseudopregnancy in the bitch. Bitches were treated orally for 5 consecutive days with one of the following dosages of mibolerone: 0.008, 0.016, or 0.025 mg/kg of body weight. Changes in psychologic signs (nesting behavior, mothering inanimate objects, and self-nursing) or physical signs (mammary gland enlargement and secretion of a liquid or milk, ie, galactorrhea) were noted. The period within which the improvement occurred also was noted. There were 63 cases distributed over the 3 dosages--19 at 0.008 mg/kg, 22 at 0.016 mg/kg, and 22 at 0.025 mg/kg. Seventeen bitches given a placebo served as controls. There were significant differences in improvement of clinical signs among the dosages for the combinations of psychologic (P less than 0.001), physical (P less than 0.01), psychologic or physical (P less than 0.001), and psychologic and physical (P less than 0.001). The projected optimal dosages were: 0.016 mg/kg, 0.013 mg/kg, 0.014 mg/kg, and 0.015 mg/kg for the psychologic, physical, psychologic or physical, and psychologic and physical signs, respectively. Of the 3 dosages used, 0.016 mg/kg (for 5 consecutive days) was estimated to be optimal for improvement of the physiologic signs of pseudopregnancy.     

Evaluation of phenylpropanolamine in the treatment of urethral sphincter mechanism incompetence in the bitch

In a multicentre, blinded, placebo-controlled trial, 50 dogs were treated for 28 days with either phenylpropanolamine or a placebo control. Each was given at a dose of one drop per 2 kg orally three times daily, equivalent to 1 mg/kg three times daily of phenylpropanolamine. Dogs that presented with clinical signs consistent with urinary sphincter mechanism incontinence were included in the study. They were examined on three occasions by the investigating veterinary surgeon. The frequency and volume of unconscious urination were scored by veterinary surgeons according to a pre-established scoring system. Phenylpropanolamine proved to be more effective than the placebo in regard to several parameters. At day 28, 85.7 per cent of phenylpropanolamine-treated cases had no episodes of unconscious urination compared with 33.3 per cent of placebo-treated cases. This was statistically significant. Few, mild side effects were seen in either group.     

Clinical, morphologic, and clinicopathologic findings in Beagles treated for two years with melengestrol acetate

Melengestrol acetate (MGA) was administered orally to groups of 10 female and 3 male Beagles at doses of 0, 1, 2, or 8 microgram/kg of body weight/day for 2 years. Treatment was continuous at the same dose rate in the first 3 groups, but in the 4th group, the dose for bitches was reduced to 4 microgram of MGA/kg/day during the 2nd year. Matings were made within MGA-dosage groups and among 10 additional bitches treated at 1 microgram of MGA/kg/day and the dogs treated at 8 microgram/kg/day. Doses of 8 and 4 microgram of MGS/kg caused progestational effects on the uterus resulting in expected histopathologic changes, dystocia, and pyometritis. Leukocytosis, normocytic, hypochromic anemia, and increased alkaline phosphatase values were the results of systemic and uterine effects consistent with the indirect and expected pharmacologic action of progestational agents in the bitch. Doses of 1 and 2 microgram of MGA/kg in dogs and bitches and 8 microgram/kg in dogs produced no significant differences in clinical observations, hematologic findings, blood chemical analysis, urinalysis, organ weights, or gross and microscopic observations at necropsy.     

Clinical evaluation of a single daily dose of phenylpropanolamine in the treatment of urethral sphincter mechanism incompetence in the bitch

The objective of this retrospective study was to determine the efficacy of a single daily oral dose of phenylpropanolamine (PPA) in the treatment of urethral sphincter mechanism incompetence (USMI) in bitches. Nine bitches diagnosed with USMI were treated with a single daily dose [1.5 mg/kg body weight (BW)] of PPA for at least 1 month. Urethral pressure profiles (UPP) were performed in 7 dogs before treatment and repeated in 4 of them after treatment. Treatment with PPA resulted in long-term continence in 8/9 bitches. One dog did not respond to PPA and was treated surgically later. Recheck UPPs showed a significant increase in maximal urethral closure pressure in the 4 bitches after treatment with PPA compared to before treatment. In conclusion, long-term continence can be achieved in bitches affected with USMI after administration of a single daily dose of PPA (1.5 mg/kg BW).     

Fenbendazole treatment of pregnant bitches to reduce prenatal and lactogenic infections of Toxocara canis and Ancylostoma caninum in pups

A granulated formulation of fenbendazole was tested in a total of 23 treated and control, pregnant, parasite-free Beagle bitches experimentally infected with Toxocara canis and Ancylostoma caninum. The drug was administered to each treated bitch once daily in canned dog food at a dosage of 50 mg/kg body weight. Each of 2 treatment regimens tested was initiated on the 40th day of pregnancy. One regimen involved daily treatment continuing through the 14th postpartum day, and it resulted in 89% fewer ascarids and 99% fewer hookworms in pups born to medicated bitches, as compared with pups born to unmedicated controls. The other regimen of treatment, which was stopped on the day of parturition, was less effective in reducing ascarid and hookworm burdens (64% and 88% reductions, respectively). Three to 5 bitches from each of the treatment and control groups were allowed to whelp a 2nd litter without further treatment or further exposure to parasite infections. Hookworm burdens in 2nd-litter pups born of bitches that had initially received fenbendazole through the 14th postpartum day were significantly lower (P < 0.01; 85% reduction), when compared with the 2nd-litter control pups. All other parasite burdens were not significantly different. It was concluded that granulated fenbendazole is effective in reducing burdens of Ancylostoma caninum and Toxocara canis in newborn pups when the bitch is treated during the last third of pregnancy, especially when treatment (50 mg/kg/day) extends from the 40th day of pregnancy through the 14th postpartum day.     

Termination of mid-term pregnancy in the dog with oral RU 486

A total of four pregnancies were terminated in three bitches (two beagles and one flatcoated retriever) with a single dose of 20 mg/kg (one case), two doses of 8-3 mg/kg (one case) or 20 mg/kg plus 40 mg/kg (two cases) RU 486 by mouth (Mifepristone; Roussel-Uclaf, France) from day 26 to day 36 after the first day of mating of the bitch. Abortions occurred within two, four, 11 and 11 days after the initial treatment, respectively. The clinical status of the bitches was similar to that observed during a normal parturition, ie, lowering of the body temperature, shivering, panting and nesting behaviour. No side effects were seen. The beagle bitch that aborted twice, was mated at the first oestrus after the first abortion, conceived and aborted the same number of puppies the second time. The peripheral plasma progesterone concentration at the time of treatment in all bitches was < 75 nmol/litre. It had decreased to between 24-2 and 13-1 nmol/litre at the time of abortion and to between 4-0 to 0–5 nmol/litre at four to 15 days after the initial treatment. Peripheral plasma levels of prolactin increased three- to fourfold within 24 to 48 hours after treatment, concomitant with the drop in progesterone and had returned to basal levels within two to three days. Prolactin concentrations also increased around the time of intrauterine fetal death. Prostaglandin F_2aα-metabolite concentrations increased slowly after treatment, and around the time of abortion the levels increased five- to 10-fold. RU 486 seems to be a safe and effective abortifacient for use during mid-term pregnancy in the dog.     

Efficacy and toxicity of tamoxifen citrate for prevention and termination of pregnancy in bitches

Five groups of bitches were given tamoxifen citrate (1 mg/kg of body weight) orally twice daily for 10 days. Drug administration commenced during late proestrus, day 4 of estrus, day 2 of diestrus, day 15 of diestrus, or day 30 of diestrus (n = 4/group). Nineteen of the bitches accepted natural mating by 1 or more of 3 stud dogs of known fertility (1 bitch did not). Twenty days after cessation of drug administration, ovarian, uterine, and hepatic specimens were obtained from each bitch in 4 of the groups. Pregnancy proceeded to natural termination in bitches of the remaining group (diestrous day 30). Pregnancy was not detected in any bitch of the proestrus, estrous, or early diestrous groups. Of 4 bitches of each of the remaining groups (diestrous day 15 and diestrous day 30), 2 aborted fetuses and/or resorbed placental remnants; the other 2 bitches in each of these groups had normal-appearing fetuses (diestrous day-15 group) or clinically normal pups (diestrous day-30 group). Of the 20 bitches given tamoxifen citrate, 5 developed endometritis with or without pyometra, and 4 of these had ovarian cysts. Although tamoxifen citrate is effective for preventing or terminating pregnancy in the bitch, the regimen used in the study reported here was associated with high frequency of pathologic changes in the reproductive tract.     

Treatment of urethral sphincter mechanism incompetence in 11 bitches with a sustained-release formulation of phenylpropanolamine hydrochloride

Between 1995 and 1999, urethral sphincter mechanism incompetence was diagnosed in 11 bitches. They had been treated with phenylpropanolamine hydrochloride at the recommended dose rate, but had shown no response or had become refractory to treatment. They were treated with phenylpropanolamine hydrochloride in a sustained-release formulation combined with diphenylpyraline hydrochloride. The urinary incontinence resolved fully in six of the bitches, two of which remained continent after the treatment was withdrawn; two showed a marked improvement on daily treatment, but the other three bitches failed to respond and underwent colposuspension.     

Megestrol acetate for estrus postponement in the bitch.

Megestrol acetate was given orally to 389 bitches in early proestrus, at a dosage of 2.2 mg/kg (1 mg/lb) per day for 8 days. Estrus was suppressed in 357 (92%) of the bitches. Additionally, 119 bitches in anestrus were given the drug at the rate of 0.55 mg/kg (0.25 mg/lb) per day for 32 days. Estrus was suppressed in 115 (98%) of these bitches. Adverse effects were minimal. Pyometra developed in 3 (0.8%) of the 389 bitches treated in early proestrus. The drug also was given to 19 bitches at the rate of 0.55 mg/kg/day for 32 days, regardless of the stage ofting at the 1st posttreatment estrus and 4 after mating at the 2nd posttreatment estrus. Litter size, success in rearing pups, and sex ratios were not significantly different from these factors in 53 litters from untreated bitches.     

乏情母犬用溴隐亭处理后的发情表现与血清中孕酮和雌二醇水平变化

选择 3只年龄为 3岁处于乏情期的苏北红犬和 6只 1～ 2岁未发情的罗威纳犬 ,用溴隐亭处理后有 4只母犬发情 ,1只母犬受孕而后流产。分析犬血清中雌二醇和孕酮水平 ,发情受孕犬雌二醇和孕酮分泌呈现规律性变化趋势 ;发情未受孕犬在雌二醇分泌峰出现后孕酮分泌不稳定 ;而未发情犬雌二醇和孕酮没有变化。结果表明 ,溴隐亭能够有效地缩短母犬的乏情期 ,溴隐亭处理后不同生理状态母犬反应差异较大 ,发过情的母犬作用明显 ,对从未发过情的母犬效果较差     

Use of low dose prostaglandin for the treatment of canine pyometra

Ten bitches with pyometra were treated with prostaglandin F_2α at a dose of 20 μg/kg bodyweight three times daily on consecutive days. Diagnosis was based on clinical signs and radiographic findings. Venous blood samples were collected for haematology and measurement of plasma progesterone levels. The response to treatment was monitored by repeated ultrasonic examinations. The treatment was continued for up to eight days. Seven out of 10 bitches responded well to treatment. The remaining three bitches underwent ovariohysterectomy and a cystic hyperplasia of the endometrium was diagnosed histologically. The results indicated that prostaglandin F_2α used at the low dose is sufficient for medical treatment of certain cases of pyometra. The treatment seems to be most effective in bitches without obvious hormonal imbalance. The aetiology of pyometra is discussed.     

Treatment of spontaneous pyometra in 22 bitches with a combination of cabergoline and cloprostenol

Twenty-two bitches with ultrasonographically diagnosed spontaneous pyometra were treated with a combination of 5 microg/kg cabergoline per day and 5 mug/kg cloprostenol every third day, and potentiated sulphonamide twice a day. Bitches with either open-cervix or closed-cervix pyometra showed a rapid clinical improvement, associated with a reduction in plasma progesterone concentration, increased vulval discharge and a reduction in the diameter of the uterus. The haematological profiles of 21 of the bitches returned to normal within six days of treatment, and their biochemical profiles returned to normal within nine days; 19 of the bitches were managed successfully by a 10-day period of treatment. Two bitches required a further three days of treatment, and in one bitch with a partial uterine torsion the treatment was not successful. Adverse effects of the treatment were limited to the 60 minutes immediately after the administration of prostaglandin, and included retching, vomiting, mild abdominal straining, diarrhoea and panting. The incidence of adverse effects was reduced after each successive dose of prostaglandin. Eleven of the 21 successfully treated bitches were mated at the next oestrus, and seven became pregnant; their litters were smaller than the published breed averages. In four of the bitches the pyometra recurred after the next oestrus.     

The effect of O,O-dimethyl-O-(2,4,5-trichlorophenyl) phosphorothioate (fenchlorphos) on cholinesterases in the blue fox (Alopex lagopus).

Four blue fox bitches were used in the experiments. Two foxes were given fenchlorphos in the feed, one 100 mg/kg body weight and the other 200 mg/kg daily for 30 days. The maximum inhibition of plasma Cholinesterase was 65 and 69 %, respectively. The corresponding values of the erythrocyte acetylcholinesterase were 43 and 63 %.For the third bitch given 0.4 mg/kg as a single dose i.v. the effect was only measurable as a small transient decrease of the plasma Cholinesterase level.Eighty % of the plasma Cholinesterase of the fourth fox, given 500 mg/kg as a single oral dose, was inhibited on the third day. The erythrocyte acetylcholinesterase activity level only showed a slight decline. This fox vomited during feeding the day after administration.Symptoms as salivation, tremors, diarrhea, pinpoint pupils and respiratory distress were never seen in any of the foxes.It was concluded that fenchlorphos administration in the feed in doses recommended to dogs is well tolerated by healthy foxes as far as Cholinesterase inhibition is concerned.     

Evaluation of a new non-hormonal substance for terminating pregnancy in bitches in clinical trials

A new non-hormonal contragestational agent (DL 717-IT), the 2-(4 chlorophenyl)-s-triazole |5,1-a|-isoquinoline, was tested in clinical trials to determine its efficacy for interrupting the pregnancy in the bitch. Five hundred and sixty-five bitches were given a single intramuscular injection of the drug between the first and 15th day after the mating. Of the 475 bitches that received 2–5 mg/kg, 430 (90-5 per cent) did not whelp at all, 15 (3-2 per cent) delivered a few stillborn or weak puppies that died some hours after birth, and 30 (6-3 per cent) delivered at least one normal live pup. Of 90 bitches treated with 3–5 mg/kg, 87 (96-7 per cent) did not whelp at all, two (2-2 per cent) delivered a few stillborn or weak puppies that died some hours after birth, and one (1 1 per cent) delivered normal live puppies. DL 717-IT, owing to the high effectiveness and minimal side effects, must be considered a very reliable drug for the interruption of pregnancies in the bitch.     

Successful Treatment for Subinvolution of Placental Sites in the Bitch with Low Oral Doses of Progestagen

Subinvolution of placental sites (SIPS) is the major cause of persistent sanguineous vaginal discharge after parturition in the bitch. Spontaneous remission is common but may take several months, and hence, medical therapy to end the discharge is often requested. In this retrospective study, we evaluated the effect of treatment for SIPS with low oral doses of a progestagen. Nine bitches with SIPS, but otherwise clinically healthy, were found in the computer database of the Department of Clinical Sciences of Companion Animals. Seven of these bitches were treated with low oral doses of a progestagen (megestrol acetate, 0.1 mg/kg body weight (bw) once daily for the 1st week, then 0.05 mg/kg bw once daily for the 2nd week). The other two bitches were untreated. Treatment results were evaluated by a telephone questionnaire. Progestagen treatment was successful in all of the treated dogs; sanguineous vaginal discharge stopped within the treatment period. One of the two untreated dogs remained symptomatic until the next oestrus, approximately 120 days after parturition, and the other remained symptomatic until 6 weeks before the start of the next pro‐oestrus, 270 days after parturition. No side effects of the progestagen treatment were observed. Subsequent gestations, parturitions and puerperal periods of 5 mated bitches were uneventful. One bitch did not become pregnant after mating. In conclusion, the results of this study indicate that oral administration of low doses of progestagen for 2 weeks is effective in stopping persistent sanguineous vaginal discharge in bitches with SIPS, with neither side effects nor reduced subsequent fertility.     

Effect and mechanisms of the anti-prolactin drug cabergoline on pseudopregnancy in the bitch

A potent anti-prolactin drug, cabergoline, administered orally for five days, was clinically successful in treating three different clinical manifestations of pseudopregnancy in referred bitches. The clinical conditions treated were categorised as standard pseudopregnant bitches (n=8), those previously unsuccessfully treated with hormones (n=10) and those which had behavioural pseudo pregnancy following ovariohysterectomy (n=8). The number of bitches whose owners reported a 'good'response was seven out of eight, six out of 10 and six out of eight, respectively. There were very few side effects in that only one bitch vomited following treatment. The clinical response did not necessarily appear to be related to an alteration in circulating prolactin concentrations, suggesting that the drug may have a direct effect on the tissues as well as in most cases reducing the plasma prolactin concentrations.     

THE INDUCTION OF OESTRUS AND OVULATION IN THE BITCH USING PREGNANT MARE SERUM GONADOTROPHIN AND HUMAN CHORIONIC GONADOTROPHIN

Seventeen bitches (11 anoestrous, 4 prepubertal, 1 pregnant and 1 postpartum) were treated with pregnant mare serum gonadotrophin (110 iu/kg) at weekly intervals up to the occurrence of oestrus or a maximum of 3 treatments. Oestrus was induced in 8/11 anoestrous bitches only. The between bitch ovarian response was very variable. Ovulation occurred in 7/8 PMSG induced oestrous bitches. The 3 oestrous bitches treated with human chorionic gonadotrophin (500 iu) at the start of oestrus had a better ovulatory response than those treated with PMSG alone.     

Equine Chorionic Gonadotropin and Human Chorionic Gonadotropin Stimulation Increase the Number of Luteinized Follicles and the Progesterone Level Compared with Cabergoline Stimulation in Anoestrus Bitches

In this study, ovarian morphologies and blood progesterone concentrations following oestrous induction in bitches were examined. Fifty‐three clinically healthy anoestrus bitches received cabergoline at a daily dose of 5 μg/kg of body weight per os for 21 days (group I) or subcutaneous equine chorionic gonadotropin at a dose of 20 IU/kg of body weight for five consecutive days with an additional 500 IU s.c. per bitch of human chorionic gonadotropin on the last day of treatment (group II). Twenty bitches that spontaneously displayed oestrous signs were left untreated and served as controls (group III). The induced oestrous rates and ovulation rates in groups I and II were 60.0% vs 64.3% and 86.7% vs 83.3%, respectively. Morphological assessments of the ovarian structures after ovariohysterectomy revealed an increase in the number of luteinized follicles and cysts in group II compared with the two other groups (p < 0.001). In contrast, the numbers of corpora lutea and follicles were similar in all groups. In accordance with the above‐mentioned alteration, the progesterone concentration in the gonadotropin group (II) was increased (p < 0.001) in the periovulatory period compared with the other two groups. During the entire sampling period, the progesterone profiles in the cabergoline (I) and control (III) groups were similar and typical of normally cycling bitches. In conclusion, gonadotropin treatment is associated with an increased progesterone level during the periovulatory period that probably originates from luteinized follicles, whereas cabergoline treatment induces cycles with both physiological progesterone concentrations and ovarian morphologies.