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Biomedical subjects

W Jöchle

Publications and source records attributed to W Jöchle.

At least 19 recordsLinked to original sources

Use of the GnRH analogue, deslorelin acetate, in a slow-release implant to accelerate ovulation in oestrous mares.

In two separate controlled clinical trials, the efficacy and safety of 2.2 mg of the GnRH analogue deslorelin, administered subcutaneously as a short-term implant to normally cycling mares in oestrus with a dominant ovarian follicle more than 30 mm in diameter, were evaluated, using a placebo as a negative control. The oestrous cycle of each mare was followed by teasing, palpation per rectum and transrectal ultrasonography. Follicles were monitored every 24 hours by ultrasonography until ovulation occurred. The mares were either mated naturally or inseminated artificially. In trial 1, 174 mares were treated at six locations in Canada, and in trial 2, 98 mares were treated at three locations in the USA. In trial 1, the treatment with deslorelin reduced the mean (sd) time to ovulation from 84.2 (48.4) hours to 50.2 (19.6) hours (P < 0.001) and in trial 2 it reduced it from 88.8 (40.3) hours to 54.1 (26.5) hours (P < 0.001). In trial 1, the percentage of mares ovulating within 48 hours increased from 37.7 per cent in control mares to 86.1 per cent in treated mares (P < 0.001) and in trial 2 the percentage increased from 26.5 to 80.9 per cent (P < 0.001). In trial 2, the duration of oestrus in the deslorelin-treated mares was reduced from 6.1 days to 4.3 days and the number of matings or artificial inseminations was reduced from 2.5 to 1.7 (P < 0.001). In trial 1, days 12 to 20 pregnancy rates for matings at the treatment oestrus were not different for deslorelin-treated (75.6 per cent) and placebo-treated (66.1 per cent) mares. In trial 2, days 12 to 20 pregnancy rates from matings at the treatment oestrus were lower for deslorelin-treated (58.7 per cent) than for placebo-treated (83.3 per cent) mares (P < 0.05), although pregnancy rates were similar for deslorelin-treated (97.1 per cent) and placebo-treated (95.0 per cent) mares after mating at the second oestrus. In both trials, pregnancy losses due to early or late abortions were within the normally expected range and similar for deslorelin-treated (3.6 and 3.7 per cent, respectively) and placebo-treated (13.4 and 7.5 per cent) mares. The treatments did not cause systemic side effects and local reactions at the implantation sites were slight and of short duration.

Animals

Clinical comparison of medetomidine with xylazine/l-methadone in dogs.

Seventy-two healthy dogs required sedation and analgesia for a variety of procedures causing discomfort or pain. They were treated either with the alpha 2-agonist medetomidine at 40 micrograms/kg (15 intravenously and 17 intramuscularly), or 80 micrograms/kg (15 intravenously and 15 intramuscularly) or with xylazine plus l-methadone (1.0 mg)(10 intravenously). The levels of sedation, analgesia and safety were compared clinically and by measurements of the effects on the electrocardiogram (ECG) and blood gases, body temperature, haematology and clinical chemistry. Sedation was achieved reliably with both medetomidine and xylazine plus l-methadone but its onset, depth and duration were influenced by the dose and route of administration. In the medetomidine-treated dogs, intravenous administration resulted in more rapid sedation and the effects of the higher dose were deeper and longer lasting. The small dogs receiving 40 micrograms/kg may have been underdosed. The initial analgesic effects in response to a pin prick to the body surface were sufficient and similar for both drugs, except for the intramuscular dose of 40 micrograms/kg medetomidine. Analgesia for the clinical procedures was less reliable with medetomidine and was not always adequate even at the high dose, but xylazine plus l-methadone assured analgesia in almost every case. Medetomidine resulted in marked bradycardia, lasting as long as the sedation and the ECG revealed a sinus arrhythmia with sinoatrial and atrioventricular blocks grade I and II as a sign of interference with transduction. The bradycardia with xylazine plus l-methadone was less pronounced. A decrease in respiratory rate accompanying sedation had no influence on blood gases and blood acidity in the dogs treated with medetomidine but caused a respiratory acidosis with xylazine plus l-methadone. Body temperature decreased with all treatments for the duration of the period of sedation. Blood glucose concentration increased to a similar extent in all treatment groups, but all other haematological and clinicochemical variables remained unchanged. Treatment with the specific alpha 2 antagonist, atipamezole, reversed the sedation and cardiovascular and pulmonary effects due to medetomidine within minutes.

Analgesics

Sedative and analgesic effects of detomidine and romifidine in horses.

In a double blind study, eight horses were treated intravenously at seven-day intervals with detomidine at doses of 10, 20 and 40 micrograms/kg, or with romifidine at doses of 40, 80 and 120 micrograms/kg, or with a placebo solution. Their sedative and analgesic effects were evaluated by objective measurements and by a clinician at 15-minute intervals for three hours and the horses' instability in stocks, locomotor ataxia and heart rate were recorded simultaneously. The administration of both drugs at all doses resulted in sedation. The sedation achieved with romifidine was significantly shallower and shorter-lived than with detomidine at the recommended doses (P < 0.05). The results obtained with the highest dose of romifidine were in some cases significantly inferior and shorter-lived than those obtained with the medium dose (P < 0.05). Detomidine at the 10 micrograms/kg dose was similar in its effects to the two highest doses of romifidine. At all doses detomidine had analgesic properties against the effects of electrical pain stimulation at the withers, the coronary bands on the front and hind legs, and in the perianal region, which were dose-dependent in depth and duration, whereas romifidine was devoid of any analgesic effect. Instability and ataxia were more pronounced with detomidine than with romifidine but the effects were only slight to moderate and not regarded as a hindrance to procedures for which sedation is needed. Bradycardia was evident with both drugs at all doses; its severity and duration was related to the sedative properties of the drugs and was dose related. No other side effects were observed.

Analgesics

[Control of ovulation in the mare with Ovuplant (short-term release of the GnRH analog deslorelin acetate). Overview of investigations from 1990 to 1994].

Ovuplant (deslorelin STI), when used in estrous mares with a follicle > or = 30 mm, reliably causes acceleration of ovulation and assurance that > 80% of the treated mares will ovulate within 48 hours. Time to ovulation is reduced by 30 hours or more. Treatment with Ovuplant had no adverse effects on pregnancy rates and did not increase the rate of early twin pregnancies. Treatment did not cause local or systemic side effects beyond short-term local irritation. Mares can be treated repeatedly without the development of tolerance or the loss of effectiveness. These studies have shown that Ovuplant can be used with a high level of assurance for success in the equine breeding industry. This will allow to reap benefits by reducing the number of breedings, saving stallion power and avoiding unnecessary inseminations. The mare has come an important step closer to a safe and effective management of ovulation.

Animals

Acceleration and timing of fertile ovulation in cyclic mares with a deslorelin implant.

In a blinded trial, the effectiveness and safety of 2.2 mg of the GnRH analog deslorelin acetate, administered in a short-term implant (STI) to normally cycling mares in estrus with a dominant ovarian follicle of 30 mm in diameter or larger, were evaluated, using a placebo implant as a negative control. A total of 39 mares received treatments at admittance with pre-randomized implants containing either 2.2 mg or 0 mg deslorelin. Mares were teased daily and examined rectally with ultrasound at 24 h intervals to determine time to ovulation and duration of estrus. The number of breedings and the pregnancy rate at 18 (+/- 3) and 38 (+/- 3) days were recorded, as were systemic side effects and local reactions at the implantation sites. Pregnancies resulting from breedings during the treatment estrus and/or from breedings during the next estrus were followed and the early and late pregnancy loss rate, the number of pregnancies going to term and of live-born foals was recorded. Mean follicle diameter at treatment was not significantly different between the deslorelin and placebo treatment group with 41.6 mm and 40.8 mm, respectively. Treatment with deslorelin STI reduced the time interval to ovulation significantly from 69.5 +/- 25.48 h to 42.7 +/- 12.35 h (p < 0.001). The percentage of mares having ovulated within 48 h rose from 26.3% to 95.0%, respectively, for placebo and deslorelin STI (p < 0.001). As a consequence, the duration of estrus in days and the percent of animals requiring more than 1 breeding were significantly reduced in deslorelin treated animals from 5.4 days to 4.6 days, and from 55.6% to 5.0%, respectively (p = 0.009 and = 0.001). The percent of mares pregnant from breedings at the treatment estrus (65.0% versus 44.4%) or the next estrus (83.3% versus 92.3%) was satisfactory and similar for deslorelin and placebo treated mares (p > 0.005), and in 70.0% and 66.7% of these once or twice bred mares did pregnancies go to term and live foals were born.

Animals

Advancing the time of ovulation in the mare with a short-term implant releasing the GnRH analogue deslorelin.

A small, biocompatible and short-term implant releasing 1.5 mg or 2.25 mg of the GnRH analogue deslorelin was evaluated in 140 Hanoverian (warm blooded) mares during the 1990 breeding season (Study I). Mares in oestrus and with a follicle 40 +/- 2 mm in diameter were assigned alternately to treatment (70) or remained as untreated controls. Implants were administered subcutaneously, and intervals to ovulation determined by rectal examination and ultrasound at 12-h intervals. Since results with both doses of deslorelin were similar, data were pooled. Deslorelin implantation resulted in ovulations in 65 of 70 mares within 48 h (93%), while only 5 of 70 control mares ovulated within the same time period (7%) (P < 0.01). Most induced ovulations (63%) occurred 36-48 h after implantation. In Study II, 4 groups of 12 Hanoverian mares each were treated with 3,000 or 5,000 iu hCG, or a 2.25 mg deslorelin implant, or received placebo. All treatments resulted in 100% ovulations within 48 h, versus 25% ovulations in controls (P < 0.01), and 63%, 75% and 86% of these ovulations occurred 36-48 h after treatment with 3,000 and 5,000 iu hCG and deslorelin respectively. Hormonal response to deslorelin in treated mares, sampled every 12 h, consisted of elevations of FSH and LH concentrations of > 200% and > 300% baseline values at 12 h (P < 0.001), of 67% and 79% at 24 h (P < 0.01) and of 35% and 49% at 48 h (P < 0.05), respectively. No local reactions at the implantation site were observed.

Alcohol Dehydrogenase

Reproduction in a feral cat population and its control with a prolactin inhibitor, cabergoline.

A feral cat population (12 females, 13 males) was observed almost daily for 6 years, at a location 40.53 degrees N and 74.29 degrees W. Cats were accustomed to twice-daily feeding. Oestrous behaviour was seasonal and started in early January, irrespective of climatic conditions, with peak levels of oestrous activities in late January and February. Of all 60 heat periods observed, and conceptions recorded, the percentage occurrence was 58 and 49 in the first quarter, and 29 and 33, 12 and 16 and 1 and 2 in the second, third and fourth quarter, respectively. Queens could be reliably identified as being pregnant by 31.5 +/- 5.82 days, and were subjected between days 36 and 57 of gestation to daily oral treatment with 5-15 micrograms cabergoline kg-1 placed on food. Treatments (n = 41) from days 36 +/- 6.17 to 40.8 +/- 6.96 resulted in abortion in all animals on day 40.5 +/- 6.19; if treatment started as late as day 48.5, and lasted 9 or more days, premature parturition occurred. As cabergoline had caused mammary gland regression within 36-48 h, litters could not be nursed and perished quickly. Five repeatedly aborted queens were subsequently allowed to go to term. Pregnancies, gestation length (64.5 days), parturitions, maternal care and lactations were normal. Of the 24 kittens born out of seven pregnancies, 16 were observed from 6 months to 3 years. Pubertal oestrus and first conceptions occurred at 189.9 days (range 150-214 days) and 212.0 days (155-277 days), respectively. Males were seen to achieve reproductive success in their third year only.

Abortifacient Agents

[The effect of the sedative and analgesic detomidine for laryngoscopy of adult horses and foals].

Detomidine was used in this field trial effectively as a sedative and analgesic for laryngoscopic examinations in a total of 193 foals and 806 mature horses (Hanoverians). Detomidine was given either i.v. in foals 3 to 11 months old (20 micrograms/kg) and in mature horses (15 micrograms/kg), or i.m. in foals below 6 months of age (35 micrograms/kg). After i.v. administration, laryngoscopy was tolerated in more than 90% of all animals without additional use of a twitch, while in foals treated i.m. more than 70% required a twitch in order to enable this procedure. The effectiveness of detomidine was influenced by dose, route of administration, the time interval between treatment and examination and the degree of excitement before treatment, but not by sex. Profound bradycardia was evident in all treated animals, but arrhythmias were seen only in animals older than 4 months and were more pronounced in horses with a lower resting heart rate. These cardiovascular responses never endangered any of the treated animals. A transient dyspnea was seen in 13 foals (6.7%) and 10 horses (1.2%). Other side effects were rare. The foaling rate of 297 mares treated at any time during the first 8 months of pregnancy was 66.7%. A comparison with 5499 untreated, contemporary controls revealed a foaling rate of 61.0%. Hence treatments had no adverse effects on pregnancies.

Analgesics

Plasma glucocorticoid concentrations in calves as an indicator of stress during parturition.

Plasma glucocorticoid concentrations and blood gas values were determined for 6 days in 47 newborn calves that had been subjected to various obstetrical procedures at term. Concentrations of glucocorticoids were uniformly high at birth (70 to 103 ng/ml). Increasing degrees of acidosis were accompanied by increasing glucocorticoid concentrations in plasma. Plasma glucocorticoid concentrations decreased sharply during the first 6 hours after delivery and reached a plateau at 48 hours after birth (14 to 21 ng/ml). The latter was taken as an indication that adaptation had been achieved. Calves subjected to severe pulling had higher glucocorticoid concentrations at birth (110.4 ng/ml) than calves requiring no assistance (88.3 ng/ml), calves requiring only slight assistance (83.8 ng/ml), or calves that had been delivered by cesarean section (82.9 ng/ml).

Acidosis

Field trial evaluation of detomidine as a sedative and analgesic in horses with colic.

In this uncontrolled clinical study 12 investigators cooperated to evaluate the analgesic and sedative effect of detomidine (DORMOSEDAN; Farmos Group Ltd; Finland) in 234 horses with abdominal pain caused by colic. The study was designed to use each animal as its own control and to evaluate its response to the drug over a 60 min period. Detomidine was given intravenously (i.v.) once in 169 cases (167 horses, 1 mule, 1 donkey) at a dose of 20 micrograms/kg bodyweight (bwt), and to 65 horses at 40 micrograms/kg bwt. The higher dose was used predominantly in horses with severe pain which were more often in poor health and therefore given a poor prognosis. Sedation and analgesia, rated as satisfactory or highly satisfactory, was achieved in 96 per cent of cases, without obvious differences between doses, sex, breed and species. First clinical signs of sedation and analgesia were recorded within 2.5 and 3.2 mins, respectively, and deep sedation and analgesia were achieved by 4.2 and 5.1 mins. Objective evaluation of analgesia was based on clinical scores related to behaviour (eg sweating, kicking, pawing, head and body movement, stretching, lip curling, attitude and appetite). In five of seven of these parameters the 40 micrograms/kg bwt treatment scored higher initially (P < 0.001) and took longer to return to normal. Although most cases treated with 20 micrograms/kg bwt returned to almost normal levels by 15 mins, those treated with 40 micrograms/kg required 30 mins. Animals not responding to either dose of detomidine went to surgery and/or were destroyed. These involved intestinal strangulation, incarceration, and torsion or rotation of the intestinal tract. No differences were found between doses in the occurrence of side effects. As expected, heart rates and respiratory rates decreased and recovered slowly. Other side effects were recorded in approximately 37 per cent of cases and consisted of instability (27.1 per cent of all other side effects), sweating (14.5 per cent), cardiovascular abnormalities (arrhythmias: 15.1 per cent) and abnormal reactions to sensorial stimuli (6.6 per cent). Less than 20 per cent of the side effects were classified as 'strong' or 'very strong' and none was considered serious. No deaths were attributed to the drug.

Analgesics

Effects on pseudopregnancy, pregnancy and interoestrous intervals of pharmacological suppression of prolactin secretion in female dogs and cats.

Cabergoline, a new ergoline derivative, is a potent prolactin inhibitor. In this review, results are combined from previously published and unpublished blind laboratory and open clinical studies with cabergoline in pseudopregnant, pregnant and lactating bitches, in bitches with normal and prolonged cycles, and in pregnant queens. Dose-response studies in nursing bitches, using puppy weight as an endpoint, revealed that a dose of 5 micrograms/kg/day orally (for 5 days) was the optimal dose with a minimum of side effects. This dose effectively lowered blood prolactin concentrations in pregnant bitches and was partly luteolytic during the 1st half of gestation, and fully luteolytic during the 2nd half of gestation. Consequently, pregnancies were terminated in the 2nd half of pregnancy in the bitch, and in the queen. Treatment successes with pseudopregnancy and true and false lactation, including cases of eclampsia, were greater than 90%. The same level of success was seen in bitches with prolonged cycles (anoestrus). A 7-10-day treatment period resulted almost uniformly in oestrus, and restored fertility in greater than 80% of all bitches mated. Cycles were occasionally shortened in bitches treated for false lactation. Attempts to shorten cycles routinely in beagle bitches, in a commercial breeding operation, with a dose of 5 micrograms/kg/day for 14 days during months 4, 5 or 6 of the cycle were unsuccessful.

Abortion, Spontaneous

Release of LH, FSH and GnRH into pituitary venous blood in mares treated with a PGF analogue, luprostiol, during the transition period.

Nine mares received cannulae to collect blood from the pituitary venous outflow in the intercavernous sinus (ICS) and the jugular vein; in 4 mares, only jugular cannulae were used. Those 4 mares and 3 of the mares with cannulae in both positions received 7.5 mg luprostiol i.m. and 1 mare with both cannulae was treated with 3.75 mg uprostiol i.v. Blood samples were kept before and after treatment at 2-, 5- or 10-min intervals and concentrations of LH, FSH and GnRH were determined by RIA. Treatments resulted in an immediate sharp rise of LH and FSH in ICS and jugular blood samples within 2-10 min, with ICS concentrations rising earlier, and with peak levels of LH 8 to 100 times higher, respectively. In ICS samples, GnRH was elevated consistently only after LH and FSH had reached peak levels. At both locations, LH and FSH concentrations remained elevated 60-120 min after treatment, but had returned to baseline by 240 min. In 5 untreated mares with cannulae at both locations, sampling at 5-min intervals for 12 or 24h revealed no pulses of LH or FSH in 3 mares, and only one pulse a day, preceded by several small rises of GnRH during the hour before the pulses, in 2 mares.

Animals