Effects of a single administration of prostaglandin F2alpha, or a combination of prostaglandin F2alpha and prostaglandin E2, or placebo on fertility variables in dairy cows 3-5 weeks post partum, a randomized, double-blind clinical trial

BACKGROUND: Delayed uterine involution has negative effects on the fertility of cows; use of prostaglandin F2alpha alone as a single treatment has not been shown to consistently improve fertility. Combined administration of PGF2alpha and PGE2 increased uterine pressure in healthy cows. We hypothesized, that the combination of both prostaglandins would accelerate uterine involution and have, therefore, a positive effect on fertility variables. In commercial dairy farming, the benefit of a single post partum combined prostaglandin treatment should be demonstrated. METHODS: 383 cows from commercial dairy farms were included in this study. Uterine size and secretion were evaluated at treatment 21-35 days post partum and 14 days later. Cows were randomly allocated to one of three treatment groups: PGF2alpha and PGE2, PGF2alpha or placebo. For every animal participating in the study, the following reproduction variables were recorded: Interval from calving to first insemination, days open, number of artificial inseminations (AI) to conception; subsequent treatment of uterus, subsequent treatment of ovaries. Plasma progesterone level at time of treatment was used as a covariable. For continuous measurements, analysis of variance was performed. Fisher's exact test for categorical non-ordered data and exact Kruskal-Wallis test for ordered data were used; pairwise group comparisons with Bonferroni adjustment of significance level were performed. RESULTS: There was no significant difference among treatment groups in uterine size. Furthermore, there was no significant difference among treatments concerning days open, number of AI, and subsequent treatment of uterus and ovaries. Days from calving to first insemination tended to be shorter for cows with low progesterone level given PGF2alpha and PGE2 in combination than for the placebo-group (P = 0.024). CONCLUSION: The results of this study indicate that the administration of PGF2alpha or a combination of PGF2alpha and PGE2 21 to 35 days post partum had no beneficial effect upon measured fertility variables. The exception was a tendency for a shorter interval from calving to first insemination after administration of the combination of PGF2alpha and PGE2, as compared to the placebo group. Further research should be done in herds with reduced fertility and/or an increased incidence of postpartum vaginal discharge.

Evaluation of administration of isoflurane at approximately the minimum alveolar concentration on depression of a nociceptive withdrawal reflex evoked by transcutaneous electrical stimulation in ponies

OBJECTIVE: To investigate effects of isoflurane at approximately the minimum alveolar concentration (MAC) on the nociceptive withdrawal reflex (NWR) of the forelimb of ponies as a method for quantifying anesthetic potency. ANIMALS: 7 healthy adult Shetland ponies. PROCEDURE: Individual MAC (iMAC) for isoflurane was determined for each pony. Then, effects of isoflurane administered at 0.85, 0.95, and 1.05 iMAC on the NWR were assessed. At each concentration, the NWR threshold was defined electromyographically for the common digital extensor and deltoid muscles by stimulating the digital nerve; additional electrical stimulations (3, 5, 10, 20, 30, and 40 mA) were delivered, and the evoked activity was recorded and analyzed. After the end of anesthesia, the NWR threshold was assessed in standing ponies. RESULTS: Mean +/- SD MAC of isoflurane was 1.0 +/- 0.2%. The NWR thresholds for both muscles increased significantly in a concentration-dependent manner during anesthesia, whereas they decreased in awake ponies. Significantly higher thresholds were found for the deltoid muscle, compared with thresholds for the common digital extensor muscle, in anesthetized ponies. At each iMAC tested, amplitudes of the reflex responses from both muscles increased as stimulus intensities increased from 3 to 40 mA. A concentration-dependent depression of evoked reflexes with reduction in slopes of the stimulus-response functions was detected. CONCLUSIONS AND CLINICAL RELEVANCE: Anesthetic-induced changes in sensory-motor processing in ponies anesthetized with isoflurane at concentrations of approximately 1.0 MAC can be detected by assessment of NWR. This method will permit comparison of effects of inhaled anesthetics or anesthetic combinations on spinal processing in equids.

Endobronchial donor pre-treatment with ventavis: is a second administration during reperfusion beneficial to optimize post-ischemic function of non-heart beating donor lungs?

BACKGROUND: Lung retrieval from non-heart-beating donors (NHBD) has been introduced into clinical practice successfully. However, because of potentially deleterious effects of warm ischemia on microvascular integrity, use of NHBD lungs is limited by short tolerable time periods before preservation. Recently, improvement of NHBD graft function was demonstrated by donor pre-treatment using aerosolized Ventavis (Schering Inc., Berlin, Germany). Currently, there is no information whether additional application of this approach in reperfusion can further optimize immediate graft function. MATERIAL AND METHODS: Asystolic pigs (n = 5/group) were ventilated for 180-min of warm ischemia (groups 1-3). In groups 2 and 3, 100 microg Ventavis were aerosolized over 30-min using an ultrasonic nebulizer (Optineb). Lungs were then retrogradely preserved with Perfadex and stored for 3-h. After left lung transplantation and contralateral lung exclusion, grafts were reperfused for 6-h. Only in group 3, another dose of 100 microg Ventavis was aerosolized during the first 30-min of reperfusion. Hemodynamics, pO2/FiO2 and dynamic compliance were monitored continuously and compared to controls. Intraalveolar edema was quantified stereologically, and extravascular-lung-water-index (EVLWI) was measured. Statistics comprised ANOVA analysis with repeated measurements. RESULTS: Dynamic compliance was significantly lower in both Ventavis groups, but additional administration did not result in further improvement. Oxygenation, pulmonary hemodynamics, EVLWI and intraalveolar edema formation were comparable between groups. CONCLUSIONS: Alveolar deposition of Ventavis in NHBD lungs before preservation significantly improves dynamic lung compliance and represents an important strategy for improvement of preservation quality and expansion of warm ischemic intervals. However, additional application of this method in early reperfusion is of no benefit.

Quality of analgesic treatment in patients with advanced prostate cancer: do we do a better job now? The Swiss Group for Clinical Cancer Research (SAKK) experience

GOALS OF WORK: The aim of this study was to evaluate pain intensity and the application of the WHO guidelines for cancer pain treatment in patients with prostate cancer treated at Swiss cancer centers. MATERIALS AND METHODS: We analyzed a series of five multicenter phase II clinical trials which examined the palliative effect of different chemotherapies in patients with advanced hormone-refractory prostate carcinoma. Of 170 patients, 1,018 visits were evaluable for our purpose, including ratings of pain intensity by patients and prescribed analgesics. MAIN RESULTS: No or mild pain was indicated by patients in 36 to 55% of the visits, more than mild pain in 30 to 46%. In 21% of the visits, the WHO pain treatment criteria (treatment according to one of the three steps; oral, rectal or transdermal application of the main dose; administration on a regular schedule) were fulfilled, and the Cleeland index was positive according to all recommendations. In 6% of the visits, neither the WHO criteria were fulfilled nor was the Cleeland index positive. This indicates insufficient pain treatment not following the WHO guidelines and that the prescribed analgesics were not sufficiently potent for the rated pain intensity. CONCLUSIONS: In this selective Swiss sample, the standard of analgesic treatment is high. However, there is still scope for improvement. This cannot solely be solved by improving the knowledge of the physicians. Programs to change the patients' attitude towards cancer pain, training to improve the physicians' communication skills, and institutional changes may be promising strategies.

Intra-articular administration of doxycycline in calves

Objective-To evaluate local tissue compatibility of doxycycline hyclate (DOX) in antebrachiocarpal joints of calves. Animals-10 healthy calves between 80 and 110 kg. Procedures-Calves were assigned to 2 treatment groups. Calves in groups DOX(low) and DOX(high) were administered 5 and 10 mg of DOX, respectively, locally in 1 antebrachiocarpal joint. The contralateral joint served as a control joint and was injected with 0.9% NaCl solution. General and local clinical findings were scored. Several variables were assessed in blood and synovial fluid for 9 days. Calves were euthanatized and pathologic changes and drug residues evaluated. Results-Throughout the study, none of the calves had clinical changes or abnormal hematologic values. Significant differences between treatment and control joints were evident only for matrix metalloproteinases at 0.5 hours after injection, with less activity for the DOX-treated joints in both treatment groups. Values for all synovial fluid variables, except nitric oxide, increased significantly during the first 12 to 72 hours after arthrocentesis in control and DOX-treated joints. Histologic examination revealed minimal infiltration of inflammatory cells independent of the treatment. No drug residues were detected 9 days after arthrocentesis in any tissues obtained from the liver, kidneys, fat, and skeletal muscles. Conclusions and Clinical Relevance-DOX had excellent intra-articular compatibility in healthy calves. Arthrocentesis induced a mild transient increase of inflammatory mediators in the synovial fluid. Significant decreases in matrix metalloproteinase activity in DOX-treated joints may indicate a potential chondroprotective effect of DOX.