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Anti-Müllerian hormone (AMH), known for its role during foetal sexual differentiation, is secreted by the Sertoli cells in males and the granulosa cells in females during post-natal life. As serum AMH concentrations correlate with follicle numbers, AMH is utilized as a marker of ovarian reserve in many species. In dogs and cats, AMH is used as a diagnostic tool to determine spay or neuter status. In the available literature, no research regarding serum AMH levels in rabbits has been published yet. The objectives of the present study were to (1) measure serum AMH concentrations in female rabbits and investigate the value of AMH as a diagnostic tool to differentiate between spayed and intact does and (2) relate measured AMH levels to pseudopregnancy and ovarian follicle numbers. For AMH measurement, serum samples were obtained from sexually intact (n = 64) and spayed (n = 22) female rabbits. Spayed does were of various breeds; intact rabbits were Zika hybrid rabbits. In the intact does, AMH measurement was complemented by determination of progesterone levels, gynaecological examination and histopathological evaluation of the uterus and ovaries, including follicle counts. Serum AMH and progesterone concentrations were measured using a human-based chemiluminescence immunoassay (CLIA) and an enzyme-linked fluorescence assay (ELFA), respectively. Depending on progesterone levels, sexually intact does were classified into follicular (n = 52) or luteal phase (n = 12). Median serum AMH levels were 1.53 ng/ml (range 0.77-3.36 ng/ml) in intact and 0.06 ng/ml (range ≤0.01-0.23 ng/ml) in spayed does. AMH concentrations between the intact and spayed rabbits differed significantly and did not overlap (p .001). Receiver operating characteristic (ROC) curve analysis yielded a sensitivity and specificity of 100% for a cut-off level of 0.50 ng/ml. Follicular or luteal phase had no significant influence on measured AMH levels (t = 0.061, df = 62, p = .951). While the number of secondary follicles correlated significantly with AMH concentrations (r

Objectives Ovarian remnant syndrome (ORS) is suspected when heat signs occur in spayed individuals, but further diagnostic procedures are necessary to exclude other possible oestrogen sources, such as the adrenal gland or exogenous supplementation. Anti-Müllerian hormone (AMH), secreted by granulosa cells or Sertoli cells, serves to differentiate sexually intact from gonadectomised animals and has been described in dogs as a tool for diagnosing ORS. The aim of this study was to evaluate if AMH determination can be used to diagnose ORS in cats. Methods AMH was measured with a chemiluminescence immunoassay in serum samples of 15 sexually intact, 9 spayed and 16 cats with a history of heat signs after spaying. Abdominal ultrasound (n = 13), vaginal smears (n = 7), progesterone measurement (n = 5) and laparotomy (n = 14) were used to determine the presence of ovarian tissue. After surgery, a histological examination of the obtained tissue was performed in the cats with suspected ORS. Results In 15 cats with ORS the AMH serum concentrations were significantly higher than in spayed cats (n = 10; P = 0.025) and significantly lower than in sexually intact cats (n = 15; P = 0.001). Among the cats with ORS, the highest AMH serum concentrations were measured in the queens with cystic ovarian alterations and in one cat from which a whole ovary was obtained. The cat with the lowest AMH serum concentration had a simultaneous high progesterone serum concentration. Cats with ORS did not show any heat signs after surgical removal of the ovarian tissue. Conclusions and relevance A single determination of AMH in blood serum is a useful diagnostic tool for the diagnosis of ORS in cats, regardless of the hormonal activity of the remnant ovarian tissue.

Studies in cats and dogs have proven the usefulness of anti-Müllerian hormone (AMH) as a diagnostic tool to determine the castration status or to diagnose ovarian remnant syndrome. Yet the secretion pattern of AMH over the estrous cycle in queens has not been investigated so far. Seven healthy sexually intact female cats were examined daily for signs of estrous behavior over a trial period of 4 months. Five queens showed regular estrous behavior, 1 queen was mated in her first heat and 1 queen never showed any signs of heat. To distinguish between inter-estrus and metestrus progesterone levels were determined. Serum samples for AMH and progesterone measurement were collected from the regular cycling queens in late anestrus, at several times during heat, inter-estrus and metestrus, from the mated queen during her first heat and during pregnancy, and in the acycling queen at various times during the trial period. The measured AMH values in anestrus were significantly (P0.05) higher than in heat (P0.001), metestrus (P = 0.12) and inter-estrus (P = 0.449). In anestrus the median AMH levels were 10.26 ng/ml (range 4.96 to 22.90 ng/ml), in heat 5.97 ng/ml (range 3.32- 22.96 ng/ml), in inter-estrus 10.47 (range 3.35-22.96 ng/ml) and in metestrus 6.38 ng/ml (range 4.50-10.75 ng/ml. The pregnant cat showed median AMH concentrations of 6.47 ng/ml (range 5.60-9.80 ng/ml) during her pregnancy. The acycling queen had solely low AMH values with a median concentration of 0.39 ng/ml. In conclusion there were high variations of the AMH levels among and within the individual cats and between heat cycles in the single cat. Remarkable high AMH concentrations were measured in the younger queens of the study in their first estrous cycles and also in anestrus, when less ovarian activity is expected. Further studies are necessary to emphasize the reasons for these high AMH concentrations especially in young queens.

An 8-year-old primiparous Labrador Retriever bitch was presented to the clinic 46 hours following the delivery of 2 vital and one stillborn puppy due to an increase of vaginal discharge. At the veterinary clinic, the dog spontaneously delivered an additional healthy puppy without any obstetric support. The findings of the general and gynaecological examinations as well as results of blood analyses were within normal limits. This case shows that extremely prolonged whelping process may be a rare but possible phenomenon in bitches. However, it is recommended to re-evaluate dam and fetuses regularly in case the inter-whelping interval exceeds the normal time span in order to recognize further signs of dystocia and induce obstetric support when clinically indicated.Eine 8-jährige erstgebärende Labrador-Retriever-Hündin wurde aufgrund von verstärktem Vaginalausfluss 46 Stunden nach der Geburt von 2 lebenden und einem toten Welpen vorgestellt. Kurz nach ihrer Ankunft gebar die Hündin spontan einen weiteren lebenden Welpen. Die allgemeine und gynäkologische Untersuchung der Mutterhündin ergaben ebenso wie eine vollständige Blutuntersuchung unauffällige Befunde. Dieser Fall zeigt, dass in Ausnahmefällen auch bei der Hündin eine extrem verlängerte Austreibungsphase möglich ist. Grundsätzlich wird jedoch empfohlen, die Hündin sowie die Feten während einer verlängerten Austreibungsphase regelmäßig zu untersuchen, um eine Veränderung der Vitalparameter rechtzeitig zu erkennen und gegebenenfalls geburtshilfliche Maßnahmen einzuleiten.

Volasertib is a selective cell cycle kinase inhibitor that induces mitotic arrest and apoptosis by targeting Polo-like kinase (Plk). A potential for prolonged QT intervals was indicated with volasertib in preclinical studies and preliminary clinical data. As a result, electrocardiograms (ECGs) have been collected in all volasertib clinical trials to monitor potential cardiac effects. This article describes strategic and statistical methods prospectively planned to perform an integrated analysis of ECG data from available trials to evaluate volasertib’s effect on cardiac repolarization, as reflected by changes in the duration of QT interval and other ECG-related endpoints. Methods to effectively cope with heterogeneity between trials (ie, differences in study designs) are discussed. These strategies may be useful for other investigational drugs for which QT risk assessment is required, but a thorough QT/QTc trial is not feasible, resulting in the need for an alternative approach. Volasertib therapy relevantly prolonged adjusted mean QTcF change from administration baseline following the first and subsequent infusions. The integrated analysis revealed that the volasertib effects on the mean QTc changes from baseline were transient and had resolved at 24 hours after start of the first infusion. There was no evidence for a long-term impact on the QTcF interval following multiple infusions with volasertib.

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Neonatal seizures are common, especially in prematurity. Phenobarbital (PB) currently represents the antiepileptic drug (AED) of choice, despite being related to increased neuronal apoptosis in animal models and cognitive impairment in human subjects. Levetiracetam (LEV) may have a more favorable profile since it does not cause neuronal apoptosis in infant rodents.In a prospective feasibility study, LEV was applied as first-line treatment in 38 newborns with EEG-confirmed seizures, after ruling out hypoglycemia, hypocalcaemia, hypomagnesaemia and pyridoxin dependency. Initial intravenous doses of 10 mg/kg LEV were gradually increased to 30 mg/kg over 3 days with a further titration to 45-60 mg/kg at the end of the week. Acute intervention with up to 2 intravenous doses of PB 20 mg/kg was tolerated during LEV titration. LEV was switched to oral as soon as the infants' condition allowed. Based on clinical observation, EEG tracings (aEEG/routine EEGs), and lab data, drug safety and anticonvulsant efficacy were assessed over 12 months.In 19 newborns a single PB dose of 20 mg/kg was administered, while 3 newborns received 2 PB doses. 30 infants were seizure free under LEV at the end of the first week and 27 remained seizure free at four weeks, while EEGs markedly improved in 24 patients at 4 weeks. In 19 cases, LEV was discontinued after 2-4 weeks, while 7 infants received LEV up to 3 months. No severe adverse effects were observed.These results illustrate the safety of LEV treatment in neonatal seizures, including prematurity and suggest LEV anticonvulsant efficacy. Additional PB treatment admittedly constitutes a methodological shortcoming due to the prolonged anticonvulsive efficacy of PB. Double blind prospective controlled studies and long-term evaluation of cognitive outcome are called for.

Background Empagliflozin is a potent, selective sodium glucose cotransporter 2 (SGLT2) inhibitor in development as an oral antidiabetic treatment. This QT interval study assessed potential effects of empagliflozin on ventricular repolarisation and other electrocardiogram (ECG) parameters. Methods A randomised, placebo-controlled, single-dose, double-blind, five-period crossover study incorporating a novel double-placebo period design to reduce sample size, while maintaining full statistical power. Treatments: single empagliflozin doses of 25 mg (therapeutic) and 200 mg (supratherapeutic), matching placebo and open-label moxifloxacin 400 mg (positive control). Triplicate 12-lead ECGs of 10 second duration were recorded at baseline and during the first 24 hours after dosing. The primary endpoint was mean change from baseline (MCfB) in the population heart rate-corrected QT interval (QTcN) between 1–4 hours after dosing. Results Thirty volunteers (16 male, 14 female, mean [range] age: 34.5 [18–52] years) were randomised. The placebo-corrected MCfB in QTcN 1–4 hours after dosing was 0.6 (90% CI: -0.7, 1.9) ms and -0.2 (-1.4, 0.9) ms for empagliflozin 25 mg and 200 mg, respectively, below the ICH E14 defined threshold of regulatory concern 10 ms. Assay sensitivity was confirmed by a placebo-corrected MCfB in QTcN 2–4 hours post-dose of 12.4 (10.7, 14.1) ms with moxifloxacin 400 mg. Empagliflozin tolerability was good for all volunteers; 23.3% experienced adverse events (AEs) with empagliflozin and 27.6% with placebo. The most frequent AE was nasopharyngitis. Conclusions/interpretation Single doses of empagliflozin 25 mg and 200 mg were not associated with QTcN prolongation and were well tolerated in healthy volunteers. Trial registration ClinicalTrials.gov: NCT01195675