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The cholecystokinin type 2 receptor (CCK2-R) represents an ideal target for cancer therapy since it is overexpressed in several tumors and is associated with poor prognosis. Nastorazepide (Z-360), a selective CCK2-R antagonist, has been widely investigated as a CCK2-R ligand for targeted therapy; however, its high hydrophobicity may represent a limit to cell selectivity and optimal in vivo biodistribution. Here, we present three new fluorescent Z-360 derivatives ( IP-002 G -Rho, IP-002 L -Rho, and IP-002 M -Rho ) in which nastorazepide was linked, through spacers bearing different saccharides (glucose (G), lactose (L), and maltotriose (M)), to sulforhodamine B. A fourth compound ( IP-002 H -Rho ) with no pendant sugar was also synthesized as a control. Through two-dimensional (2D) and three-dimensional (3D) in vitro studies, we evaluated the compound association with and selectivity for CCK2-R-overexpressing cells (A431-CCK2-R + ) vs CCK2-R-underexpressing cells (A431 WT). 2D in vitro studies highlighted a progressive increase of IP-002 x -Rho association with A431-CCK2-R + cells according to the linker hydrophilicity, that is, maltotriose > lactose > glucose > hydrogen, with IP-002 M -Rho showing a 2.4- and a 1.36-fold higher uptake than IP-002 G -Rho and IP-002 L -Rho , respectively. Unexpectedly, IP-002 H -Rho showed a similar cell association to that of IP-002 L -Rho but with no difference between the two tested cell lines. On the contrary, association with A431-CCK2-R + cells as compared to the A431 WT was found to be 1.08-, 1.14-, and 1.37-fold higher for IP-002 G -Rho , IP-002 L -Rho , and IP-002 M -Rho , respectively, proving IP-002 M -Rho to be the best-performing compound, as also confirmed by competition studies. Trafficking studies on A431-CCK2-R + cells incubated with IP-002 M -Rho suggested the coexistence of receptor-mediated endocytosis and simple diffusion. On the contrary, a high and selective uptake of IP-002 M -Rho by A431-CCK2-R + cells only was observed on 3D scaffolds embedded with cells, underlining the importance of 3D models in in vitro preliminary evaluation.

Objective: To compare the analgesic effect of a bilateral ultrasound-guided erector spinae plane block (ESPB) in dogs undergoing hemilaminectomy using either a low-volume high-concentration (LV-HC) or a high-volume low-concentration (HV-LC) local anaesthetic solution., Study Design: Retrospective observational equivalence trial., Animals: A total of 391 client-owned dogs undergoing hemilaminectomy., Methods: Dogs were assigned to group LV-HC or HV-LC depending on whether 0.2-0.25% levobupivacaine (0.4-0.5 mL kg -1 ) or 0.125-0.15% levobupivacaine (0.8-1 mL kg -1 ) was used to perform the ESPB, respectively. The number of dogs in which intraoperative rescue fentanyl boluses were administered, the total dose of fentanyl administered, the overall methadone consumption during the first 24 hours postoperatively and anaesthetic complications were recorded. Univariate and multivariate statistical analyses were performed considering p < 0.05 significant., Results: A total of 248 and 143 dogs were assigned to groups LV-HC and HV-LC, respectively. In group HV-LC, the number of dogs requiring fentanyl intraoperatively (64.3%) was higher (p = 0.0001) than that in group LV-HC (43.5%). The overall intraoperative fentanyl consumption was higher in group HV-LC between the first skin incision and the end of the lamina drilling (p = 0.028). According to the regression analysis, the group allocation was the best variable to predict the intraoperative fentanyl consumption (p < 0.001). Antimuscarinic drugs were administered more frequently in group LV-HC (p < 0.02). However, the prevalence of hypotension and other pharmacological cardiovascular interventions did not differ between groups. No differences in methadone consumption during the first 24 hours postoperatively were found between the groups., Conclusionsand Clinical Relevance: When performing a bilateral ESPB in dogs undergoing hemilaminectomy, compared with HV-LC, the use of LV-HC local anaesthetic solution reduces the intraoperative fentanyl consumption without affecting the postoperative methadone requirement., (Copyright © 2024 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.)

The aim of the present study consists of the evaluation of the biodistribution of a novel 68 Ga-labeled radiopharmaceutical, [ 68 Ga]Ga-NODAGA-Z360, injected into Balb/c nude mice through histopathological analysis on bioptic samples and radiomics analysis of positron emission tomography/computed tomography (PET/CT) images. The 68 Ga-labeled radiopharmaceutical was designed to specifically bind to the cholecystokinin receptor (CCK2R). This receptor, naturally present in healthy tissues such as the stomach, is a biomarker for numerous tumors when overexpressed. In this experiment, Balb/c nude mice were xenografted with a human epidermoid carcinoma A431 cell line (A431 WT) and overexpressing CCK2R (A431 CCK2R+), while controls received a wild-type cell line. PET images were processed, segmented after atlas-based co-registration and, consequently, 112 radiomics features were extracted for each investigated organ / tissue. To confirm the histopathology at the tissue level and correlate it with the degree of PET uptake, the studies were supported by digital pathology. As a result of the analyses, the differences in radiomics features in different body districts confirmed the correct targeting of the radiopharmaceutical. In preclinical imaging, the methodology confirms the importance of a decision-support system based on artificial intelligence algorithms for the assessment of radiopharmaceutical biodistribution.

Background: Transdermal delivery of highly lipophilic molecules is challenging due to the strong barrier function of the skin. Vesicles with penetration enhancers are safe and efficient systems that could improve the transdermal delivery of non-psychoactive cannabinoids such as cannabidiol and desoxy-cannabidiol. In the last decades, research interest in desoxy-cannabidiol as a potent drug with anti-nociceptive properties has risen. Still, its scarce market availability poses a limit for both research and clinical applications. Therefore, it is necessary to improve the synthesis to produce sufficient amounts of desoxy-cannabidiol. Moreover, also the formulation aspects for this drug are challenging and require to be addressed to meet an efficient delivery to the patients., Objective: This work aimed to develop innovative phospholipid-based vesicles with propylene glycol (PG), oleic acid (OA), or limonene as edge activators, for the transdermal delivery of highly lipophilic drugs such as non-psychoactive cannabinoids. In particular, desoxy-cannabidiol was selected thanks to its anti-nociceptive activity, and its synthesis was improved enhancing the stereoselectivity of its synthon's production., Methods: Desoxy-cannabidiol was synthesized by Lewis acid-mediated condensation of p-mentha-2,8-dien- 1-ol and m-pentylphenol, improving the stereoselectivity of the first synthon's production. Transethosomes containing 20-50% w/w PG, 0.4-0.8% w/w OA, or 0.1-1% w/w limonene were optimized and loaded with cannabidiol or desoxy-cannabidiol (0.07-0.8% w/w, 0.6-7.0 mg/mL). Ex-vivo studies were performed to assess both the skin permeation and accumulation of the cannabinoids, as well as the penetration depth of fluorescein- loaded systems used as models., Results: An enantioselective bromination was added to the pathway, thus raising the production yield of pmentha- 2,8-dien-1-ol to 81% against 35%, and the overall yield of desoxy-cannabidiol synthesis from 12% to 48%. Optimized transethosomes containing 0.6 mg/mL cannabinoids were prepared with 1:10 PG:lipid weight ratio, 0.54 OA:lipid molar ratio, and 0.3 limonene:lipid molar ratio, showing good nanometric size (208 ± 20.8 nm - 321 ± 26.3 nm) and entrapment efficiency (> 80%). Ex-vivo tests showed both improved skin permeation rates of cannabinoids (up to 21.32 ± 4.27 μg/cm2 cannabidiol), and skin penetration (depth of fluorescein up to 240 μm, with PG)., Conclusion: Desoxy-cannabidiol was successfully produced at high yields, and formulated into transethosomes optimized for transdermal delivery. Loaded vesicles showed improved skin penetration of desoxy-cannabidiol, cannabidiol and a lipophilic probe. These results suggest the potential of these carriers for the transdermal delivery of highly lipophilic drugs., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objective: To assess the effects of intravenous (IV) fentanyl on cough reflex and quality of endotracheal intubation (ETI) in cats., Study Design: Randomized, blinded, negative controlled clinical trial., Animals: A total of 30 client-owned cats undergoing general anaesthesia for diagnostic or surgical procedures., Methods: Cats were sedated with dexmedetomidine (2 μg kg -1 IV), and 5 minutes later either fentanyl (3 μg kg -1 , group F) or saline (group C) was administered IV. After alfaxalone (1.5 mg kg -1 IV) administration and 2% lidocaine application to the larynx, ETI was attempted. If unsuccessful, alfaxalone (1 mg kg -1 IV) was administered and ETI re-attempted. This process was repeated until successful ETI. Sedation scores, total number of ETI attempts, cough reflex, laryngeal response and quality of ETI were scored. Postinduction apnoea was recorded. Heart rate (HR) was continuously recorded and oscillometric arterial blood pressure (ABP) was measured every minute. Changes (Δ) in HR and ABP between pre-intubation and intubation were calculated. Groups were compared using univariate analysis. Statistical significance was set as p < 0.05., Results: The median and 95% confidence interval of alfaxalone dose was 1.5 (1.5-1.5) and 2.5 (1.5-2.5) mg kg -1 in groups F and C, respectively (p = 0.001). The cough reflex was 2.10 (1.10-4.41) times more likely to occur in group C. The overall quality of ETI was superior in group F (p = 0.001), with lower laryngeal response to ETI (p < 0.0001) and ETI attempts (p = 0.045). No differences in HR, ABP and postinduction apnoea were found., Conclusions and Clinical Relevance: In cats sedated with dexmedetomidine, fentanyl could be considered to reduce the alfaxalone induction dose, cough reflex and laryngeal response to ETI and to improve the overall quality of ETI., (Copyright © 2023 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.)

Background: Erector spinae plane block (ESPB) is an ultrasound-guided interfascial plane block used to provide analgesia in dogs undergoing hemilaminectomy. The aim of this study is to compare the analgesic efficacy of a bilateral ESPB with a fentanyl constant rate infusion (CRI) in dogs undergoing hemilaminectomy., Methods: This is a retrospective cohort study. Anaesthetic records of client-owned dogs undergoing hemilaminectomy (June 2019-August 2020), and in which a bilateral ESPB was performed (group ESPB), were retrieved and compared to a cohort of 39 dogs that underwent hemilaminectomy (September 2014 - June 2017) and in which a fentanyl CRI (2 μg/kg bolus followed by 5 μg/kg/hour) was used as a primary intraoperative analgesia (group CRI). The prevalence of dogs in which intraoperative rescue fentanyl boluses were administered, the total dose of rescue fentanyl boluses administered, the postoperative methadone requirement and anaesthetic complications during the first 24 postoperative hours were evaluated. Univariate statistical analysis was used., Results: Group ESPB comprised of 93 dogs. The bilateral ESPB was performed using a median (range) levobupivacaine volume of 1 (0.5-1.7) mL/kg per side, at a concentration of 0.125% (0.12-0.25). At least one rescue fentanyl bolus was administered in 54.8% and in 56.4% of dogs in group ESPB and CRI, respectively (p > 0.99). The number of rescue fentanyl boluses was higher in group CRI (p = 0.006), especially during lumbar hemilaminectomy. Rescue fentanyl boluses were more frequently administered from skin incision to end of vertebral lamina drilling in group CRI (p = 0.001), and from end of vertebral lamina drilling to end of surgery in group ESPB (p = 0.0002). During the first 6 (p = 0.0035) and 6-12 (p = 0.0005) postoperative hours, the number of dogs that required at least one dose of methadone was higher in group CRI. In group ESPB, dogs were more likely to become hypothermic (p = 0.04). One dog, not included in the study, developed sinus arrest after performing a caudal thoracic ESPB., Conclusions: Under the conditions of this study, a bilateral ESPB was associated with a lower number of rescue fentanyl boluses administered in dogs undergoing hemilaminectomy, especially between skin incision to end of vertebral lamina drilling. Despite ESPB being associated with a reduced opioid consumption during the first 12 hours postoperatively, differences in the postoperative management precluded any firm conclusion regarding its postoperative effect., (© 2022. The Author(s).)

Background: To describe the use of a bilateral thoracic (T5 - T9) ultrasound-guided erector spinae plane block (UG-ESPB) in dogs undergoing sternotomy anaesthetised with propofol and dexmedetomidine continuous infusions., Methods: Demographic information, perioperative anaesthetic and analgesic drugs, the prevalence of hypotension and nociceptive events, and their treatment, were recorded and analysed. Local anaesthetic injection point, volume and concentration were reported for each dog. In attempt to differentiate somatic nociception from visceral nociception, the surgery was divided into three timeframes: from the skin incision to the thoracic cavity opening; from the latter to the beginning of its closure; from thoracic cavity closure to the end of surgery., Results: Overall, 10 dogs were included and four experienced nociception: somatic nociception was recorded in one dog, whereas visceral nociception was recorded in four dogs. The overall fentanyl consumption to control nociception was 0.3 µg/kg/h. No adverse events associated with the UG-ESPB were reported., Conclusion: The bilateral UG-ESPB could be used as a part of a multimodal analgesic technique in dogs undergoing sternotomies. However, more clinical studies are warranted to assess its safety and effects., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Objectives: To assess the effects of extradural anaesthesia-analgesia (EAA) in dogs undergoing cholecystectomy., Materials and Methods: Medical records of dogs undergoing cholecystectomy between 2011 and 2019 were retrieved and allocated to two groups depending if analgesia was provided systemically (group SA) or extradurally (EAA). Preoperative data, intraoperative antinociceptive medications, postoperative analgesia, perioperative complications, and food intake were compared., Results: Overall 41 medical records were included in the study: 19 and 22 dogs were allocated to groups SA and EAA, respectively. In group EAA, an extradural catheter was placed preoperatively in 8 dogs; in the remaining, it was placed postoperatively but an extradural injection was performed preoperatively. The extradural catheter tip was between the 4th lumbar and the 10th thoracic vertebrae. Intraoperatively, nociception was more likely to occur in group SA [OR 55.42 (2.97-1,035.06)]. During the first 24 and 48 h postoperatively, more dogs in group SA required methadone [OR 24 (2.81-268.4) and OR 11.56 (2.37-45.06), respectively] and additional analgesic drugs [OR 25 (3.47-281.9) and OR 35.29 (1.86-668.2), respectively] compared to group EAA. Voluntary postoperative food intake was also significantly higher in group EAA., Clinical Significance: Compared to systemic analgesia, the use of extradural anaesthesia-analgesia reduced perioperative analgesic requirement and promoted postoperative food intake in dogs undergoing cholecystectomy., Competing Interests: Authors BS, CD, RH, and EV were employed by Linnaeus Veterinary Limited., (Copyright © 2022 Sambugaro, De Gennaro, Hattersley and Vettorato.)

Background: The usefulness of routine follow-up Magnetic Resonance Imaging (MRI-2) in asymptomatic dogs treated for discospondylitis is unknown., Methods: This cross-sectional retrospective study investigated the features of MRI-2 in a heterogeneous group of dogs treated for discospondylitis, and if these were associated with the presence or absence of clinical signs. After comparing initial MRI (MRI-1) and MRI-2, an observer, blinded to the dog's clinical signs, described the MRI-2 findings. The study population was then divided into symptomatic or asymptomatic at the time of MRI-2. Two separate observers subjectively classified the discospondylitis as active or inactive. Repeatability and interobserver agreement were evaluated., Results: A total of 25 dogs were included. At the time of MRI-2 16 (64%) dogs were asymptomatic and 9 (36%) were symptomatic. Based on MRI-2, 20 (80%) and 18 (72%) out of 25 dogs were considered to have active discospondylitis by the first and second observers, respectively. Interobserver agreement was moderate. No MRI-2 features were associated with the clinical status. The subjective classification of inactive discospondylitis was significantly associated with asymptomatic clinical status, but the classification of active discospondylitis was evenly distributed between groups., Conclusion: This study did not identify a meaningful association between the clinical status of dogs treated for presumptive discospondylitis and MRI-2 results. There were no specific MRI-2 features which were associated with the clinical status., Competing Interests: All authors were employed by company Dick White Referrals, part of Linnaeus Veterinary Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 de Freitas, Vettorato, Scarpante, Cherubini and Caine.)

Objective:  The aim of this study was to retrospectively evaluate the success rate and perioperative complications of lumbosacral extradural anaesthesia in dogs undergoing total hip replacement., Study Design:  Records of dogs undergoing total hip replacement in which lumbosacral extradural anaesthesia with 0.5% levo- or bupivacaine combined with either morphine or buprenorphine were retrieved. Success rate was defined as intraoperative fentanyl consumption <1 μg/kg/h with no intravenous infusion of other analgesic drugs and no additional morphine/methadone within the first 3 hours from premedication. Prevalence of intraoperative anaesthetic and postoperative surgical complications was calculated., Results:  Overall, 206 dogs were included in the study. Success rate was 88.7%. Hypercapnia (75.2%), hypotension (46.1%), hypothermia (27.7%) and regurgitation (6.3%) were recorded during anaesthesia. Within 24 hours post-surgery, urinary retention (17.8%), vomiting/regurgitation/diarrhea (8.2%) and sciatic neurapraxia of the operated limb (5.8%) were recorded. Luxation of the operated hip occurred at 48 and 72 hours after surgery in two dogs and one dog respectively. One dog had cardiopulmonary arrest at 52 hours after surgery., Conclusion:  While hypercapnia, hypotension and hypothermia might develop intraoperatively, the high success rate and the relatively low prevalence of postoperative surgical complications directly associated with lumbosacral extradural anaesthesia justify its use in dogs undergoing total hip replacement., Competing Interests: None declared., (Thieme. All rights reserved.)

This retrospective study assessed the effect of an intraoral bilateral maxillary nerve block in dogs undergoing surgery for brachycephalic obstructive airway syndrome (BOAS). Records of dogs that underwent BOAS surgery were retrieved. Cases were assigned to Group B or C if a preoperative bilateral maxillary nerve block was performed or not. Type and dose of local anesthetic, inhalant anesthetic minimum alveolar concentration multiples, intraoperative fentanyl and injectable anesthetic use, prevalence of intraoperative hypotension or bradycardia, and postoperative opioids administration, were compared between groups. Sixty-seven cases met the inclusion criteria: 33 were assigned to Group B and 34 to Group C. In Group C, 18 dogs required intraoperative fentanyl ( P = 0.005), and 12 needed injectable anesthetic top-ups ( P = 0.006). Hypotension, or bradycardia, were not different between groups. Bilateral maxillary nerve block reduces intraoperative fentanyl and injectable anesthetic requirement in dogs undergoing BOAS surgery., (Copyright and/or publishing rights held by the Canadian Veterinary Medical Association.)

Background: Apart from the absence of nociception, there is no readily available prognostic test for dogs presenting with paraplegia secondary to acute intervertebral disc extrusion (IVDE)., Objective: To assess if serum C-reactive protein (CRP) can predict the postoperative outcome in paraplegic dogs undergoing surgery for IVDE and to assess the association between serum CRP and presence/absence of nociception on admission, and serum CRP and presence/absence of intramedullary changes seen on magnetic resonance imaging (MRI)., Animals: One hundred dogs that underwent surgery at our hospital between 2018 and 2020 because of acute paraplegia secondary to IVDE and in which serum CRP was measured., Methods: Retrospective observational cohort study. Dogs were classified as 4 or 5 according to the modified Frankel score (MFS) depending on presence/absence of nociception, respectively. MRI images were reviewed and the T2-weighted hyperintensity: L2 vertebral body length was measured. Postoperative outcome was defined as positive if nociception, ambulation or both returned after decompressive surgery., Results: The median (95% CI) serum CRP was 4 (4-5) and 6 (4-7) mg/L in MSF4 and MSF5, respectively (P = .03). A weak linear relationship (R 2  = 0.049, P = .03) was found between CRP and the T2-weighted hyperintensity: L2 vertebral length. Outcome data was available for 85 dogs: CRP was 4 (4-5) and 5 (4-10) mg/L in positive and negative outcome dogs, respectively (P = .32)., Conclusion and Clinical Importance: Serum CRP did not predict outcome after surgery in dogs with paraplegia secondary to IVDE., (© 2021 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Coronavirus disease 2019 (COVID-19) is a new viral disease complicating with acute thrombophylic conditions, probably also via an inflammatory burden. Anticoagulants are efficacious, but their optimal preventive doses are unknown. The present study was aimed to compare different enoxaparin doses/kg of body weight in the prevention of clot complications in COVID-19 pneumonia. Retrospective data from a cohort of adult patients hospitalized for COVID-19 pneumonia, never underwent to oropharyngeal intubation before admission, were collected in an Internal Medicine environments equipped for non-invasive ventilation. Unfavorable outcomes were considered as: deep venous thrombosis, myocardial infarction, stroke, pulmonary embolism, cardiovascular death. Fourteen clinical thromboembolic events among 42 hospitalized patients were observed. Patients were divided into two group on the basis of median heparin dose (0.5 mg-or 50 IU-for kg). The decision about heparin dosing was patient by patient. Higher enoxaparin therapy (mean 0.62±0.16 mg/kg) showed a better thromboprophylactic action (HR=0.2, p=0.04) with respect to lower doses (mean 0.42±0.06 mg/kg), independently from the clinical presentation of the disease. Therefore, COVID-19 pneumonia might request higher enoxaparin doses to reduce thromboembolic events in hospitalized patients, even if outside intensive care units., Competing Interests: Competing interests: None declared., (© American Federation for Medical Research 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

The cholecystokinin-2 receptor (CCK-2R) is overexpressed in several human cancers but displays limited expression in normal tissues. For this reason, it is a suitable target for developing specific radiotracers. In this study, a nastorazepide-based ligand functionalized with a 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) chelator (IP-001) was synthesized and labelled with indium-111. The radiolabeling process yielded >95% with a molar activity of 10 MBq/nmol and a radiochemical purity of >98%. Stability studies have shown a remarkable resistance to degradation (>93%) within 120 h of incubation in human blood. The in vitro uptake of [ 111 In]In-IP-001 was assessed for up to 24 h on a high CCK-2R-expressing tumor cell line (A549) showing maximal accumulation after 4 h of incubation. Biodistribution and single photon emission tomography (SPECT)/CT imaging were evaluated on BALB/c nude mice bearing A549 xenograft tumors. Implanted tumors could be clearly visualized after only 4 h post injection (2.36 ± 0.26% ID/cc), although a high amount of radiotracer was also found in the liver, kidneys, and spleen (8.25 ± 2.21%, 6.99 ± 0.97%, and 3.88 ± 0.36% ID/cc, respectively). Clearance was slow by both hepatobiliary and renal excretion. Tumor retention persisted for up to 24 h, with the tumor to organs ratio increasing over-time and ending with a tumor uptake (1.52 ± 0.71% ID/cc) comparable to liver and kidneys.

Research in the field of radiopharmaceuticals is increasingly promoted by the widespread and growing interest in applying nuclear medicine procedures in both disease diagnosis and treatment. The production of radionuclides of medical interest is however a challenging issue. Along with the conventional techniques other innovative approaches are being investigated and, among those, the ISOLPHARM project is being developed at INFN-LNL (Istituto Nazionale di Fisica Nucleare - Laboratori Nazionali di Legnaro). Such technique foresees the employment of the SPES ISOL facility to produce isobarically pure Radioactive Ion Beams (RIBs), obtained thanks to electromagnetic mass separation and collected on appropriate substrates. The latter are successively recovered and dissolved, allowing thus the chemical separation and harvesting of the nuclides of interest, free from any isotopic contaminant. Although ISOLPHARM can be potentially employed for most of the routinely used medical radioisotopes, its innovation potential is better expressed considering its capability to provide carrier free unconventional nuclides, difficult to produce with state-of-art techniques, such as 111 Ag, a β - emitter potentially interesting for therapeutic applications. Thus, in the framework of ISOLPHARM, INFN supported a two-years experiment, called ISOLPHARM&#95;Ag, aimed at evaluating the feasibility of the production of a 111 Ag labelled radiopharmaceutical. The ISOL production yields are estimated by computing intensive Monte Carlo codes, that require an appropriate custom Information Technology infrastructure. The presented work is focused on the first part of the production chain including the capability to extract, ionize, and collect stable Ag beams with SPES technologies. MC calculations were used to estimate the expected 111 Ag in-target yields, whereas experiments with stable Ag were performed to test the ionization, transport and collection of Ag beams., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objective: To compare the effects of intravenous (IV) lidocaine and fentanyl on the cough reflex and autonomic response during endotracheal intubation in dogs., Study Design: Randomized, blinded, superiority clinical trial., Animals: A total of 46 client-owned dogs undergoing magnetic resonance imaging., Methods: After intramuscular methadone (0.2 mg kg -1 ), dogs were randomized to be administered either IV lidocaine (2 mg kg -1 ; group L) or fentanyl (7 μg kg -1 ; group F). After 5 minutes, alfaxalone was administered until endotracheal intubation was possible (1 mg kg -1 IV over 40 seconds followed by 0.4 mg kg -1 increments to effect). Total dose of alfaxalone was recorded and cough reflex at endotracheal intubation was scored. Heart rate (HR) was continuously recorded, Doppler systolic arterial blood pressure (SAP) was measured every 20 seconds. Vasovagal tonus index (VVTI) and changes (Δ) in HR, SAP and VVTI between pre-intubation and intubation were calculated. Groups were compared using univariate and multivariate analysis. Statistical significance was set as p < 0.05., Results: Group F included 22 dogs and group L 24 dogs. The mean (± standard deviation) alfaxalone dose was 1.1 (± 0.2) and 1.35 (± 0.3) mg kg -1 in groups F and L, respectively (p = 0.0008). At intubation, cough was more likely in group L (odds ratio = 11.3; 95% confidence intervals, 2.1 - 94.2; p = 0.01) and HR increased in 87.5% and 54.5% of groups L and F, respectively (p = 0.02). The median (range) ΔHR between pre-intubation and intubation was higher (13.1%; - 4.3 to + 55.1) in group L (p = 0.0021). Between groups, SAP and VVTI were similar., Conclusion and Clinical Relevance: At the stated doses, whilst reducing the alfaxalone dose, fentanyl is superior to lidocaine in suppressing the cough reflex and blunting the increase in HR at endotracheal intubation in dogs premedicated with methadone., (Copyright © 2020 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.)

This study reports the clinical use of two sevoflurane-based anesthetic techniques in dogs undergoing craniectomy. Twenty-one animals undergoing elective rostrotentorial or transfrontal craniectomy for brain tumor excision, anesthetized with sevoflurane, were enrolled in this retrospective, observational study. Anesthetic records were allocated to two groups: Sevo-Op (sevoflurane and short acting opioid infusion): 8 dogs and Sevo-Dex (sevoflurane and dexmedetomidine infusion): 13 dogs. Average mean arterial pressure (MAP), heart rate, end-tidal carbon dioxide, end-tidal sevoflurane and intraoperative infusion rates during surgery were calculated. Presence of intra-operative and post-operative bradycardia, tachycardia, hypotension, hypertension, hypothermia, hyperthermia was recorded. Time to endotracheal extubation, intraoperative occurrence of atrioventricular block, postoperative presence of agitation, seizures, use of labetalol and dexmedetomidine infusion were also recorded. Data from the two groups were compared with Fisher's exact test and unpaired t tests with Welch's correction. Odds ratio (OR) and 95% confidence interval (CI) were calculated for categorical variables. Intra-operatively, MAP was lower in Sevo-Op [85 (± 6.54) vs. 97.69 (± 7.8) mmHg, p = 0.0009]. Time to extubation was longer in Sevo-Dex [37.69 (10-70) vs. 19.63 (10-25), p = 0.0033]. No differences were found for the other intra-operative and post-operative variables investigated. Post-operative hypertension and agitation were the most common complications (11 and 12 out of 21 animals, respectively). These results suggest that the infusion of dexmedetomidine provides similar intra-operative conditions and post-operative course to a short acting opioid infusion during sevoflurane anesthesia in dogs undergoing elective rostrotentorial or transfrontal intracranial surgery., Competing Interests: The authors declare no conflicts of interest., (© 2020 The Korean Society of Veterinary Science.)

Objective: To compare the perioperative effects and pharmacoeconomics of peripheral nerve blocks (PNBs) versus fentanyl target-controlled infusion (fTCI) in dogs undergoing tibial plateau levelling osteotomy (TPLO)., Study Design: Randomized clinical study., Animals: A total of 39 dogs undergoing unilateral TPLO., Methods: After acepromazine and methadone, anaesthesia was induced with propofol and maintained with isoflurane. Dogs were allocated to group fTCI [target plasma concentration (TPC) 1 ng mL -1 ] or group PNB (nerve stimulator-guided femoral-sciatic block using 0.2 and 0.1 mL kg -1 of levobupivacaine 0.5%, respectively). If nociceptive response occurred, isoflurane was increased by 0.1%, and TPC was increased by 0.5 ng mL -1 in group fTCI; a fentanyl bolus (1 μg kg -1 ) was administered in group PNB. During the first 24 postoperative hours, methadone (0.2 mg kg -1 ) was administered intramuscularly according to the Short Form Glasgow Composite Pain Scale, or if pain was equal to 5/24 or 4/20 for two consecutive assessments, or if the dog was non-weight bearing. The area under the curve (AUC) of pain scores, cumulative postoperative methadone requirement, food intake and pharmacoeconomic implications were calculated., Results: Incidence of bradycardia (p = 0.025), nociceptive response to surgery (p = 0.041) and AUC of pain scores (p < 0.0001) were greater in group fTCI. Postoperatively, 16/19 (84.2%) and eight/20 (40%) dogs in groups fTCI and PNB, respectively, were given at least one dose of methadone (p = 0.0079). Food intake was greater in group PNB (p = 0.049). Although total cost was not different (p = 0.083), PNB was more cost-effective in dogs weighing >15 kg., Conclusions and Clinical Relevance: Compared with group fTCI, incidence of bradycardia, nociceptive response to surgery, postoperative pain scores, cumulative methadone requirement were lower, and food intake was greater in group PNB, with an economic advantage in dogs weighing >15 kg., (Copyright © 2019 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.)

Age-related hippocampal formation (HF) atrophy has been documented on MRI studies using volumetric analysis and visual rating scales.This retrospective cross-sectional study aimed to compare linear MRI measurements of the HF between young (1-3 years) and old (>10 years) non-brachycephalic dogs, with normal brain anatomy and cerebrospinal fluid (CSF) analysis. Right and left hippocampal formation height (HFH), height of the brain (HB) and mean HFH/HB ratio were measured by two observers on a transverse T2 fluid-attenuated inversion recovery sequence containing rostral colliculi and mesencephalic aqueduct.119 MRI studies were enrolled: 75 young and 44 old dogs. Left and right HFH were greater (p<0.0001) in young, while HB was greater in old dogs (p=0.024). Mean HFH/HB ratio was 15.66 per cent and 18.30 per cent in old and young dogs (p<0.0001). No differences were found comparing measurements between epileptic and non-epileptic dogs.Old dogs have a greater HB; this may represent the different study populations or a statistical phenomenon. Ageing affects HF linear measurements. A reduction of mean HFH/HB ratio between 18.30 per cent and 15.66 per cent should be considered a physiological age-related process of the canine lifespan. The use of mean HFH/HB ratio could be considered for quantifying brain atrophy in elderly dogs., Competing Interests: Competing interests: None declared., (© British Veterinary Association 2019. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ.)

Ethosomes are nanovesicular carriers for dermal administration. Phospholipids, ethanol at relatively high concentrations (up to 50%) and water are their main components. Ethosomes are what we call "soft vesicles" with fluid bilayers due to the presence of ethanol. The composition and structure of the vesicles augment their ability to entrap molecules with various physicochemical properties and deliver them to the deep strata of skin. Since their first design, ethosomal systems have been extensively investigated for a wide range of applications. This review focuses on work carried out in vitro, in vivo in animal models and in humans in clinical studies, with ethosomal formulations containing natural active molecules for the treatment of skin disorders. Skin bacterial and fungal infections, skin inflammation, acne vulgaris, arthritis, and skin cancer are examples of disorders managed successfully by ethosomal systems. Furthermore, Ethosomes loaded with a number of naturally occurring compounds for cosmetic applications are also reported. The efficient treatments together with a good safety profile and lack of toxicity or irritation paved the way towards the development of new dermal therapies., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objective: To compare the efficacy and side effects of postoperative methadone administered according to pain score (PS) or every 4 hours (Q4), after unilateral uncomplicated tibial plateau levelling osteotomy (TPLO) in dogs in which a peripheral nerve block (PNB) was administered., Study Design: Retrospective, case-control study., Animals: Clinical records of dogs that underwent a TPLO in 2015 were retrieved; 136 out of 174 dogs were included: 52 assigned to group PS, 84 to group Q4., Methods: In group PS, methadone was administered according to the short form of the Glasgow Composite Measure Pain Scale (CMPS-SF), whereas in group Q4 methadone was administered at 4 hour intervals. Demographic data, anaesthetic technique, surgery time, American Society of Anesthesiologists classification, PNB performed, local anaesthetic used and dose, anti-inflammatory drugs administered, end-expiratory fraction of isoflurane, perioperative opioid consumption, time to first postoperative methadone administration, pain scores, time to first pain score, food intake, number of postoperative observations, presence/absence of specific keywords representing the general state and behaviour of the animal, use of the operated limb and reaction to wound palpation were retrieved. Fisher's exact test, chi-square test, Student t test or Mann-Whitney U test were used, considering p<0.05 significant. Odds ratios and 95% confidence intervals were calculated, when indicated., Results: Four times more methadone was administered to dogs in group Q4, and whilst not having lower pain scores or better short-term outcome (e.g. toe-touching and weight bearing), were 23.42 times (1.37 to 400.40) more likely to vomit, 3.76 (1.50 to 9.49) more likely to vocalize, and their food intake was 38% less than dogs in group PS. No dogs in group PS vomited postoperatively., Conclusions and Clinical Relevance: Administration of methadone Q4 caused more side effects than administration guided by CMPS-SF. This should be considered when planning postoperative analgesia in dogs undergoing uncomplicated TPLO and in which a PNB has been performed., (Copyright © 2018 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.)

Objectives The objective of this study was to compare the sedative effect of butorphanol-dexmedetomidine with buprenorphine-dexmedetomidine following intramuscular (IM) administration in cats. Methods Using a prospective, randomised, blinded design, 40 client-owned adult cats were assigned to receive IM dexmedetomidine (10 µg/kg) combined with either butorphanol (0.4 mg/kg) ('BUT' group) or buprenorphine (20 µg/kg) ('BUP' group). Sedation was scored using a previously published multidimensional composite scale before administration (T0) and 5, 10, 15 and 20 mins afterwards (T5, T10, T15 and T20, respectively). Alfaxalone (1.5 mg/kg) was administered IM at T20 if the cat was not deemed adequately sedated to place an intravenous catheter. Adverse events were recorded. Friedman two-way ANOVA analysed sedation scores within groups. Mann-Whitney Rank Sum test compared sedation scores between groups; Fisher's exact test analysed the frequency of alfaxalone administration and adverse events. P <0.05 was considered statistically significant. Results Sedation scores between groups were similar at baseline, but at T5, T10, T15 and T20 scores were higher in the BUT group ( P <0.01). Within both groups, sedation scores changed over time and the highest sedation scores were reached at T10. Requirement for additional sedation was similar between groups: two cats in the BUT group and five cats in the BUP group. One cat and 11 cats vomited ( P = 0.002) in the BUT and BUP groups, respectively. No other adverse events were recorded. Conclusions and relevance At these doses, IM buprenorphine-dexmedetomidine provides inferior sedation and a higher incidence of vomiting than butorphanol-dexmedetomidine in cats. Butorphanol-dexmedetomidine may be preferred for feline sedation, especially where vomiting is contraindicated.

A cat that underwent bilateral ventral bulla osteotomy (VBO) for treatment of otitis media and otitis interna secondary to bilateral inflammatory polyps, developed upper airway obstruction (UAO) soon after tracheal extubation. The cat was re-intubated but the UAO did not resolve at the next extubation. Eventually, tracheostomy was performed. Upper airway obstruction is a potential postoperative complication of bilateral VBO in cats.

Aim: We aimed to assess the performance of the National Early Warning Score (NEWS) as tool for patient risk stratification at admission in an acute Internal Medicine ward and to ensure patient placement in ward areas with the required and most appropriate intensity of care. As secondary objective, we considered NEWS performance in two subgroups of patients: sudden cardiac events (acute coronary syndromes and arrhythmic events), and chronic respiratory insufficiency., Methods: We conducted a perspective cohort single centre study on 2,677 unselected patients consecutively admitted from July 2013 to March 2015 in the Internal Medicine ward of the hospital of Trento, Italy. The NEWS was mandatory collected on ward admission. We defined three risk categories for clinical deterioration: low score (NEWS 0-4), medium score (NEWS 5-6), and high score (NEWS≥7). Following adverse outcomes were considered: total and early (<72 hours) in-hospital mortality, urgent transfers to a higher intensity of care. A logistic regression model quantified the association between outcomes and NEWS., Results: For patients with NEWS >4 vs patients with NEWS <4, the risk of early death increased from 12 to 36 times, total mortality from 3.5 to 9, and urgent transfers from 3.5 to 7. In patients with sudden cardiac events, lower scores were significantly associated with higher risk of transfer to a higher intensity of care. In patients affected by chronic hypoxaemia, adverse outcomes occurred less in medium and high score categories of NEWS., Conclusions: National Early Warning Score assessed on ward admission may enable risk stratification of clinical deterioration and can be a good predictor of in-hospital serious adverse outcomes, although sudden cardiac events and chronic hypoxaemia could constitute some limits., (© 2017 John Wiley & Sons Ltd.)

Objectives: The aim of this study was to assess retrospectively the efficacy and complication rate of hindlimb peripheral nerve blocks (PNBs) in cats., Methods: Clinical records of cats that received PNBs and underwent hindlimb orthopaedic surgery from February 2010 to October 2014 were examined. Type of PNB, type and dose of local anaesthetic used, end-expiratory fraction of isoflurane (FE'Iso) administered, additional intraoperative analgesia, incidence of hypotension, postoperative opioid requirement, postoperative contralateral limb paralysis and neurological complications at the 6 week re-examination were investigated., Results: Eighty-nine records were retrieved but only 69 were analysed. Four combinations of PNBs were used: 34 lateral preiliac (LPI) approach to lumbar plexus (LP) associated with lumbar paravertebral approach to sciatic nerve (SN); 20 LPI-LP associated with the lateral approach to SN; three LPI-LP associated with gluteal approach to SN; 12 dorsal-paravertebral (DPV) approach to LP associated with lateral SN. Levobupivacaine was used for the majority of PNBs. The mean intraoperative FE'Iso was 1.15%; hypotension was documented in 55.1% of anaesthetics, while 31.8% of cats received fentanyl and/or ketamine intraoperatively. Postoperatively, 72.7% of cats received at least one dose of opioid, while five cats required further postoperative analgesia (ketamine constant rate infusion and/or gabapentin). No cats showed contralateral limb paralysis and neurological complications at the 6 week re-examination. No differences were found when comparing the different PNBs used., Conclusions and Relevance: PNBs contributed to perioperative anaesthesia/analgesia in cats undergoing hindlimb orthopaedic surgery. However, the clinical relevance of intraoperative hypotension needs further investigation., (© The Author(s) 2015.)

Purpose: To characterise changes in vertebral dimension in an ovine model of scoliosis and determine whether a reproducible curvature could be created that would be suitable for future testing of curve modifying surgical implants., Methods: At a mean age of 5 weeks, 28 Scottish blackface sheep were anaesthetised. A 4 mm braided synthetic tape was laid under the left lamina of T5 and L1 and tightened to 'hand' tension. A scoliosis was then created by binding the six lowest ribs on the same side just distal to their rib angles and resecting a segment from each of the opposite ribs. Radiographs were taken at 4 weekly intervals, and CT images at 2, 5 and 7 months post tethering, to determine multi-planar curve progression. 20 animals were assessed at age 3 months, 12 at 41 weeks and 10 at 1 year with comparisons to five control animals., Results: A significant bi-planar deformity was produced in all animals (scoliosis 32 ± 13º and lordosis 53 ± 21º 2 months post tethering; mean ± SD, n = 22). During the next 5 months the scoliosis decreased slightly (p = 0.08) but the sagittal deformity remained static: 21 ± 18° and 53 ± 19°, respectively (n = 12). The values at 7 months were associated with a mean 6 ± 4º rotational deformity. There was approximately twice as much growth in the right anterior aspects of the apical vertebrae as in the left posterior., Conclusions: With appropriate care it was possible to obtain a reproducible curvature in immature sheep. The methods described are suitable for use in studies of growth modulation and other spinal devices.

Purpose: First, to determine whether scoliosis development could be limited or reversed by growth when a novel modular hinged implant was fixed to the convexity of a scoliosis created by contralateral rib and laminar tethering and unilateral rib resection in a sheep model. Second, to assess the effect and performance of the implant in normal non-tethered sheep., Methods: At 5 weeks, 20 Scottish Blackface lambs underwent surgery to create a right sided scoliosis by (i) tethering the left lamina of T5-L1 and the left lower six ribs and (ii) resecting a segment of their right lower six ribs [1, 2]. Twelve weeks later, through an antero-lateral thoracotomy, a mobile bi-planar hinged implant was inserted onto the right side of the spine of eight animals (group 1). For comparison, 12 sheep were tethered only but had no implant insertion (group 2). In addition, seven had no tethering but were implanted (group 3) and normal growth patterns were observed in five that had no surgery (group 4). Curve progression was assessed by plain radiography and CT over a 1-year period., Results: Before implant insertion the trial animals had a scoliosis of 35º ± 16º and a lordosis of 44º ± 20º (n = 8, mean ± SD). Surgery immediately reduced these values to 25º ± 14º, p < 0.01 and 35º ± 18º, p < 0.001, with scoliosis continuing to decrease during the next three months. Spinal flexibility was retained. In the un-tethered sheep, a scoliosis of 10º ± 6º was created on the opposite side to the implant (p < 0.05) with no significant change in alignment in the sagittal plane (1º ± 6º). The implant did not cause any adverse effect on growth or affect neurological function., Conclusions: In the un-tethered animals the effect of the implant was to create a scoliotic deformity and in the tethered to improve deformity while maintaining spinal motion. We believe that the results are promising and that devices of similar construct may be of use in children with scoliosis, potentially changing current methods of clinical care.

Objective: To compare the effect of alfaxalone and propofol on heart rate (HR) and blood pressure (BP) after fentanyl administration in healthy dogs., Study Design: Prospective, randomised clinical study., Animals: Fifty healthy client owned dogs (ASA I/II) requiring general anaesthesia for elective magnetic resonance imaging for neurological conditions., Methods: All dogs received fentanyl 7 μg kg(-1) IV and were allocated randomly to receive either alfaxalone (n = 25) or propofol (n = 25) to effect until endotracheal (ET) intubation was possible. Heart rate and oscillometric BP were measured before fentanyl (baseline), after fentanyl (Time F) and after ET intubation (Time GA). Post-induction apnoea were recorded. Data were analysed using Fisher's exact test, Mann Whitney U test and one-way anova for repeated measures as appropriate; p value <0.05 was considered significant., Results: Dogs receiving propofol showed a greater decrease in HR (-14 beat minute(-1) , range -47 to 10) compared to alfaxalone (1 beat minute(-1) , range -33 to 26) (p = 0.0116). Blood pressure decreased over the three time periods with no difference between groups. Incidence of post-induction apnoea was not different between groups., Conclusion: Following fentanyl administration, anaesthetic induction with propofol resulted in a greater negative chronotropic effect while alfaxalone preserved or increased HR., Clinical Relevance: Following fentanyl administration, HR decreases more frequently when propofol rather than alfaxalone is used as induction agent. However, given the high individual variability and the small change in predicted HR (-7.7 beats per minute after propofol), the clinical impact arising from choosing propofol or alfaxalone is likely to be small in healthy animals. Further studies in dogs with myocardial disease and altered haemodynamics are warranted., (© 2014 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.)

Objective: To investigate the effect of intraoperative extradural morphine administration on postoperative analgesia in dogs undergoing thoracolumbar spinal surgery to treat disk extrusion., Design: Prospective clinical trial., Animals: 26 client-owned dogs undergoing thoracolumbar spinal surgery., Procedures: Animals were randomly allocated to receive morphine (0.1 mg/kg [0.045 mg/lb], extradurally) or no treatment (control group). Following preanesthetic medication with methadone (0.25 mg/kg [0.11 mg/lb], IM), anesthesia was induced with propofol and maintained with isoflurane or sevoflurane in oxygen. Lidocaine and fentanyl were administered during surgery in both groups at fixed rates. In the morphine administration group, morphine was splashed over the dura mater immediately prior to wound closure. Postoperative analgesia was assessed for 48 hours by assessors unaware of group allocation, and methadone was administered as rescue analgesic. Demographic characteristics, urinary output, days of hospitalization, and perioperative use of analgesics were compared via a Mann-Whitney U test., Results: Demographic data were similar between groups. In the morphine administration group, 2 of 13 dogs required postoperative methadone, and in the control group, methadone was administered to 11 of 13 dogs. The total number of doses of methadone administered in the 48 hours after surgery was 28 in the control group and 3 in the morphine administration group. No adverse effects were recorded in any group., Conclusions and Clinical Relevance: Intraoperative extradural morphine administration was effective in reducing postoperative analgesic requirement. Dogs undergoing thoracolumbar spinal surgery benefited from topical administration of preservative-free morphine administered directly on the dura mater as part of analgesic management.

Objective: To compare isoflurane and sevoflurane in lambs undergoing prolonged anaesthesia for spinal surgery., Study Design: Prospective randomised clinical study., Animals: Eighteen Scottish blackface lambs 3-6 weeks of age and weighing 10-17 kg., Methods: After intramuscular medetomidine, anaesthesia was induced and maintained with either isoflurane (group I) or sevoflurane (group S) delivered in oxygen. Meloxicam, morphine, a constant rate infusion of ketamine and atracurium were given intravenously (IV) during surgery. Lungs were ventilated to maintain normocapnia. with peak inspiratory pressures of 20-25 cmH(2) O. Ephedrine or dextran 40% was administered when mean arterial pressure (MAP) was <55 mmHg. Intrathecal morphine, and IV meloxicam and edrophonium were injected before recovery. Time to loss of palpebral reflex (TLPR) upon induction, cardiorespiratory variables, time at first swallowing and other movement, tracheal extubation, vocalisation, spontaneous head lifting (>1 minute), reunion with the ewe, and the number of MAP treatments were recorded. Statistical analysis utilised anova, Mann-Whitney, t-test or Pearson's correlation test as relevant. p < 0.05 was considered significant., Results: End-tidal carbon dioxide (mean ± SD) was significantly lower in group S (5.5 ± 0.6 kPa) than in group I (5.8 ± 0.5 kPa) while MAP (70 ± 11 mmHg) and diastolic arterial blood pressure (60 ± 11 mmHg) were higher in group S than in group I (65 ± 12 and 54 ± 11 mmHg, respectively). No differences were found with TLPR and MAP treatments. Time (median, range) from end of anaesthesia to ewe-lamb reunion was briefer (p = 0.018) in group S (48, 20-63 minutes)., Conclusion: Isoflurane and sevoflurane are both suitable for maintaining general anaesthesia in lambs although sevoflurane, as used in this study, allows a more rapid reunion with the ewe., Clinical Relevance: The principal advantage of sevoflurane over isoflurane during prolonged anaesthesia in lambs is a more rapid recovery., (© 2012 The Authors. Veterinary Anaesthesia and Analgesia. © 2012 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesiologists.)

Objective: To determine the effects of age, sevoflurane and isoflurane on atracurium-induced neuromuscular blockade in 3-16 week-old lambs., Study Design: Prospective randomized experimental trial., Animals: Twenty-six Scottish blackface ewe-lambs were anaesthetized for spinal surgery when either 3-6 (mean age 4.6 weeks; n = 18) or 12-16 weeks (mean age 13.7 weeks; n = 15) of age; seven animals were anaesthetized at both ages., Methods: After intramuscular injection of medetomidine (10 μg kg(-1)) anaesthesia was induced in the younger lambs either with isoflurane or sevoflurane in oxygen delivered by mask, and in the older lambs with ketamine (4 mg kg(-1)), and midazolam (0.2 mg kg(-1) ) administered intravenously (IV). In both groups anaesthesia was maintained with fixed end-tidal concentrations of either sevoflurane (2.8%) or isoflurane (1.8%) delivered in oxygen. Before surgery meloxicam (0.6 mg kg(-1)), morphine (0.5 mg kg(-1)) and ketamine (1 mg kg(-1) followed by 10 μg kg(-1) minute(-1) ) were administered IV. The lungs were ventilated mechanically to maintain normocapnia. Neuromuscular block was achieved with a loading dose (LD) of atracurium (0.5 mg kg(-1) IV). The peroneal nerve was stimulated (train-of-four every 12 seconds). Evoked responses in the digital extensor muscles were evaluated by palpation and observation. Maintenance doses (MD) of atracurium (0.17 mg kg(-1) IV) were administered when the first twitch (T1) returned. The onset and duration of LD action (T1 absent) and the duration of MD were recorded. Data were analysed using Student's t test, Mann-Whitney U test, repeated-measures anova, Wilcoxon's matched pairs test or Pearson correlation coefficient as relevant (p < 0.05)., Results: Onset of LD action developed significantly (p < 0.05) more rapidly in isoflurane compared with sevoflurane-anaesthetized lambs (55 ± 18 cf. 80 ± 37 seconds). Duration of action of LDs and MDs was longer (p < 0.05) in lambs aged 12-16 than 3-6 weeks (33 ± 5.4 cf. 25 ± 6.4 and 26 ± 4.2 cf. 18 ± 5.5 minutes) but were independent of the anaesthetic used., Conclusions and Clinical Relevance: The effect of atracurium is age-dependent in lambs being prolonged in older animals. The onset of neuromuscular blockade is more rapid in isoflurane compared with sevoflurane-anaesthetized lambs., (© 2012 The Authors. Veterinary Anaesthesia and Analgesia. © 2012 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesiologists.)

Objective: To evaluate the success rate and complications of lumbar plexus (LP) and femoral nerve (FN) blocks, each combined with a sciatic nerve (SN) block, in dogs undergoing pelvic limb orthopaedic surgery., Design: Retrospective clinical study., Procedure: The intra-operative and postoperative clinical records of dogs that underwent orthopaedic surgery of the pelvic limb were reviewed. Dogs were divided into two groups according to the analgesic technique used during surgery: dogs that received a peripheral nerve block (group PNB) and dogs in which opioid analgesia alone was used (group C)., Results: The PNB and C groups included 265 and 31 dogs, respectively. Complete statistical analysis was performed in 115/265 dogs of PNB group. The overall success rate of the PNB performed was 77% (89/115): 76% (72/95) and 85% (17/20) for LP-SN and FN-SN blocks, respectively. In group PNB, the prevalence of intra-operative hypotension was 7.8% (9/115). Only one (out of 95 [1.05%]) LP-SN block manifested transient postoperative bilateral pelvic limb paralysis. None of the 265 dogs in group PNB manifested neurological complications at six weeks postoperatively., Conclusion: The success rate and the absence of neurological complications obtained support the use of LP-SN and FN-SN for loco-regional anaesthesia and analgesia in dogs undergoing orthopaedic surgery of the pelvic limb.

Observations: A 12 year old cat was presented for anaesthesia to remove a mandibular squamous cell carcinoma. After intramuscular premedication with dexmedetomidine and methadone, anaesthesia was induced with alfaxalone, administered intravenously (IV) to effect, and maintained with isoflurane vaporized in oxygen, following oro-tracheal intubation. Approximately 5 minutes after performing a mandibular nerve block with 1.16 mg kg(-1) of bupivacaine, the cat developed severe cardiovascular depression. Anaesthetic delivery was discontinued and cardiopulmonary resuscitation instituted. Drug administration consisted of atropine (0.02 mg kg(-1) IV, repeated three times), followed by atipamezole (0.08 mg kg(-1) IV). Dobutamine was subsequently administered (1 μg kg(-1) minute(-1) IV) until cardiovascular performance was considered satisfactory. During recovery from anaesthesia the cat exhibited seizure-like activity, which was controlled by a variable rate infusion of propofol. The cat made an uneventful recovery following discontinuation of propofol infusion, without residual neurological signs, and the surgical procedure was postponed., Conclusions: This clinical report describes successful management of cardiovascular and neurological complications following a mandibular nerve block with bupivacaine in a cat. Although treatment was successful, the role played by the drugs administered during resuscitation remains uncertain., (© 2011 The Authors. Veterinary Anaesthesia and Analgesia. © 2011 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesiologists.)

Introduction: Anaesthesia in lambs undergoing experimental surgery may develop problems associated with age-related immune incompetency: a postoperative complication in a 3 week old Scottish blackface lamb after spinal surgery is presented. CASE HISTORY AND MANAGEMENT: Both lamb and ewe were in good condition. The ewe was vaccinated against Clostridium perfringens and Clostridium tetani 5 weeks pre-partum. There were no apparent problems with the lamb's intake of colostrum. Pre-anaesthetic medication was intramuscular medetomidine (10 μg kg(-1)). Anaesthesia was induced and maintained with sevoflurane in oxygen. Morphine (0.5 mg kg(-1)), meloxicam (0.6 mg kg(-1)) and ketamine (1 mg kg(-1) followed by 10 μg kg(-1) minute(-1)) were administered intravenously (IV) for perioperative analgesia. Atracurium (0.5 mg kg(-1) IV, followed by 0.17 mg kg(-1) injected when the first twitch of the four, train-of four count was palpated) was used to improve muscle relaxation. The lamb's trachea was intubated and the lungs mechanically ventilated to maintain normocapnia. Intrathecal morphine (0.2 mg kg(-1)), IV meloxicam (0.3 mg kg(-1)) and edrophonium (0.5 mg kg(-1)) were administered before recovery. Operative and initial recovery periods were unremarkable. Three hours after surgery the lamb became depressed. Tachycardia (180-250 beats minute(-1)), tachypnoea (30 breaths minute(-1)), poor peripheral perfusion and cold pelvic limb extremities were present mimicking severe pain, and/or hypovolaemic shock. Analgesics - morphine (total dose 1.3 mg kg(-1)) - and IV fluid therapy boluses - crystalloids (300 mL), colloids (120 mL) and fresh whole blood (60 mL) - failed to ameliorate clinical signs and so the lamb was euthanized 10 hours after surgery. Post-mortem findings supported a possible diagnosis of peracute Clostridium perfringens enterotoxaemia., Conclusion: Clostridium perfringens enterotoxaemia should be considered when clinical signs of severe pain and/or hypovolaemic shock fail to respond to analgesics and fluid resuscitation in lambs after major surgery., (© 2011 The Authors. Veterinary Anaesthesia and Analgesia © 2011 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesiologists.)

Tramadol is a synthetic opioid agonist used extensively in human and, to a lesser extent, veterinary medicine throughout the world. The clinical efficacy and pharmacokinetic profile of intravenous (i.v.) and extradural (e.d.) tramadol (2 mg/kg) and its o-desmethyl metabolite were studied in dogs undergoing tibial plateau levelling osteotomy (TPLO). Intra-operative cardiorespiratory variables were monitored and post-operative pain was assessed using the short form of the Glasgow Composite Pain Scale. A rapid (<5 min) and effective production of o-desmethyl tramadol was recorded. The pharmacokinetic profile was similar for tramadol and its metabolite irrespective of the route of administration. E.d. tramadol provided sufficient intra- and post-operative analgesia without significant clinical side-effects, but the post-operative analgesia was comparable to that following i.v. administration and the e.d. route could therefore not be considered a practical alternative to the i.v. route., (2008 Elsevier Ltd. All rights reserved.)