Cardiorespiratory, Sedative and Antinociceptive Effects of a Medetomidine Constant Rate Infusion with Morphine, Ketamine or Both

Standing surgery under sedation reduces anesthetic-related mortality in horses. Medetomidine, alone and combined with morphine in a constant rate infusion (CRI), has been described for standing surgery but their cardiorespiratory, sedative and antinociceptive effects have never been compared. The addition of ketamine could improve analgesia in these procedures with minimal cardiorespiratory consequences. The objectives were to compare the cardiorespiratory effects, quality of sedation, antinociception and ataxia produced by administration of a medetomidine-based CRI with morphine, ketamine or both, in standing horses. A prospective, blind, randomized crossover, experimental design with six healthy adult horses was performed, in which four treatments were administered to all horses with at least two weeks of washout period: medetomidine (M); medetomidine and ketamine (MK); medetomidine and morphine (MMo); and medetomidine, morphine and ketamine (MMoK). Dosages were the same in all treatment groups: medetomidine at 5 µg/kg bwt followed by 5 µg/kg bwt/h, ketamine at 0.4 mg/kg/h and morphine at 50 µg/kg bwt, followed by morphine 30 µg/kg bwt/h. Drug infusions were maintained for 120 min. Cardiorespiratory variables, sedation degree and antinociceptive effects were evaluated during the procedure. All combinations produced similar sedation and antinociceptive effects and no clinically relevant alterations in cardiorespiratory variables occurred. Medetomidine CRI combined with morphine, ketamine or both are suitable and safe protocols for standing sedation in horses and the addition of morphine and/or ketamine did not cause any negative effect but no improving effect on sedation and antinociception was detected

Oral bisphosphonate-related osteonecrosis of the jaws : clinical characteristics of a series of 20 cases in Spain

Objective: The objective of this study was to define the clinical characteristics of osteonecrosis of the jaws (ONJ) induced by oral bisphosphonates in a series of patients from a circumscribed area in northwest Spain. Study Design: A retrospective multicentre study was undertaken in 3 hospitals in an area with a radius less than 100 km in the Autonomous Community of Galicia (Spain). The medical records were reviewed and an oral examination was performed of patients diagnosed with oral bisphosphonate-related ONJ in the previous 3 years. Results: We detected 20 cases of ONJ (24 lesions) related to oral bisphosphonates (alendronate [16 patients] and ibandronate [4 patients]), which were mainly administered as treatment for osteoporosis (17 patients). The mean interval between initiation of treatment and confirmation of a diagnosis of ONJ was 66±43 months (range, 6-132 months); in 7 patients (35%) the interval was less than 36 months. The past history revealed hypertension in 13 cases (65%) and diabetes in 4 (20%); 7 patients (35%) were on corticosteroid treatment. Oral surgery had been previously performed in 13 patients (65%) and the remaining 7 patients (35%) had removable dental prostheses. The lesions most frequently affected the posterior mandible (62.5%). The majority of the lesions (75%) were classified as stage 2, although lesions were identified in all established clinical stages (including 2 stage 0 lesions). Conclusion: In conclusion, in the present series, ONJ induced by oral bisphosphonates typically develops in women around 70 years of age, taking alendronate, that underwent oral surgery. Most lesions are located in the posterior mandible and are classified as stage 2 at diagnosis. Some patients presented no known risk factors, suggesting that there may be risk factors still to be identified. There are well-defined patterns of clinical presentation that can facilitate early diagnosis of ONJ

Morphine with or without Acepromazine in Horses: A Kinematic Evaluation

Morphine is an opioid agonist drug and produces a significant analgesic effect in horses but besides the evidenced analgesic effect, the use of morphine is not routine due to the potential excitatory effects described in the literature. To minimize these effects, neuroleptanalgesia, or the combination of opioids and sedative drugs, is encouraged. Our aim was to describe changes occurring in the locomotor pattern after co-administration of a tranquilizer, acepromazine, and morphine in horses. Six mature horses were used and received four different treatments with saline solution, morphine, acepromazine, or a combination of morphine and acepromazine. A three-dimensional accelerometric device was used to collect data and objectivize those findings moreover the sedative effect of the treatments was also measured. Significant differences were observed when comparing all the treatments in the majority of accelerometric variables, except the regularity of the pattern, some energetic parameters, and tranquilization. An evident counteraction of the effects caused by both morphine and acepromazine was observed. Due to these effects, the possibility of adding acepromazine to an additional analgesic treatment with morphine in the clinical setting ensures the absence of the supplemental instability caused by other sedatives and minimizes the potential opioid excitatory effects

Changes in the requirement for early surgery in inflammatory bowel disease in the era of biological agents

This is the peer reviewed version of the following article: Changes in the requirement for early surgery in inflammatory bowel disease in the era of biological agents. Journal of Gastroenterology and Hepatology (2020): 29 April, which has been published in final form at https://doi.org/10.1111/jgh.15084. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived VersionsBiological therapies may be changing the natural history of inflammatory bowel diseases, reducing the need for surgical intervention. We aimed to assess whether the availability of anti‐TNF agents impacts the need for early surgery in Crohn's disease (CD) and ulcerative colitis (UC). Methods Retrospective, cohort study of patients diagnosed within a 6‐year period before and after the licensing of anti‐TNFs (1990‐1995 and 2007‐2012 for CD; 1995‐2000 and 2007‐2012 for UC) were identified in the ENEIDA Registry. Surgery‐free survival curves were compared between cohorts. Results A total of 7,370 CD patients (2,022 in Cohort 1 and 5,348 in Cohort 2) and 8,069 UC patients (2,938 in Cohort 1 and 5,131 in Cohort 2) were included. Immunosuppressants were used significantly earlier and more frequently in both CD and UC post‐biological cohorts. The cumulative probability of surgery was lower in CD following anti‐TNF approval (16% and 11%, 22% and 16%, and 29% and 19%, at 1, 3 and 5 years, respectively p<0.0001), though not in UC (3% and 2%, 4% and 4%, and 6% and 5% at 1, 3 and 5 years, respectively; p=0.2). Ileal involvement, older age at diagnosis and active smoking in CD, and extensive disease in UC, were independent risk factors for surgery, whereas high‐volume IBD centres (in both CD and UC) and immunosuppressant use (in CD) were protective factors. Conclusions Anti‐TNF availability was associated with a reduction in early surgery for CD (driven mainly by earlier and more widespread immunosuppressant use) but not in U

Culture conditions and investigation of bioreactor configurations for lipase production by rhizopus oryzae

Lipolytic enzymes are the subject of great industrial and academic interest. For this reason, a detailed study of lipolytic enzyme production by the fungus Rhizopus oryzae is tackled, and several steps from plate to shake flasks and bioreactor cultures are investigated in order to propose an optimized strategy to perform the biological process. The suitability of several lipidic compounds and surfactants is assessed. Triton X-100 (5 g/L) gives the highest activities with a maximum value of 6320 U/L which is 10-fold the value attained in cultures without addition of lipidic compounds. As there are almost no studies on bench-scale bioreactors, two bioreactor configurations, stirred tank and air-lift, are investigated to determine the most suitable one to carry out the biological reaction. It is demonstrated that the lipolytic activity is strongly enhanced when a stirred-tank bioreactor is used with a maximum value of 3521 U/L within two days which is clearly higher than the values produced by other recently reported species.XUNTA de Galicia | Ref. PGIDIT06 PXIB314376P

Treatments and Prognosis for Subchondral Cystic Lesions in the Distal Extremities in Thoroughbred Prospect Racehorses

Subchondral cystic lesions (SCLs) in equines and their treatments have been mainly studied in the medial femoral condyle of the femur. SCLs in the distal extremities affecting the fetlock or interphalangeal joints are frequent, but treatment or prognosis studies in horses are currently sparse. Our objective was to compare four treatments for SCLs in the distal extremities (intralesional injection of corticosteroids, transcortical drilling, cortical screw placement, and absorbable hydroxyapatite implant placement) and report the racing prognoses for affected thoroughbred yearlings. Data from 113 thoroughbred yearlings treated for SCLs in the distal extremities were collected from 2014 to 2020. Age at surgery, sex, bone affected, radiographic SCL measurements, SCL shape, and type of treatment were recorded. Sale data and racing performance were collected for the operated horses and for 109 maternal siblings that were free of SCLs. An analysis was conducted to assess if SCL size affected racing prognosis and to detect differences in sale value and selected racing parameters between the cases and controls. The outcomes for the different treatments, the different bones affected, and the SCL shape type were also analyzed. There was no difference in the ability to start in a race between the cases and controls (60.2% vs. 69.7%, respectively). The auction value of the treated horses was significantly lower than that of their siblings. The bone affected did not impact any of the racing variables studied, whereas the height of the SCLs negatively affected the number of wins and placed races. The type of treatment for the horses affected by SCLs did not have an impact on sale prices, ability to start a race, race starts, wins, and places, or age at the time of the first start. In conclusion, yearlings diagnosed with an SCL in the distal extremities had lower auction prices and decreased racing performances, with lower numbers of wins correlated with larger SCL heights compared to the siblings. Similar racing performance was found regardless of the treatment received

Electromyographic and ultrasonographic evaluation of neuromuscular electrical stimulation training on the equine rectus abdominis muscle

The current study aimed to determine the effects of neuromuscular electrical stimulation (NMES) on equine rectus abdominis using surface electromyography (sEMG) and ultrasonographic muscle thickness evaluation. Five horses were trained with NMES for 12 weeks; muscle thickness and sEMG evaluations were obtained before and after the training period. Three different tests were carried out for sEMG evaluations: Test A tried to elicit a voluntary maximal isometric contraction (VMIC); Test B used NMES to elicit a muscular contraction; and Test C used 1 ms repetitive electrical impulses to elicit a series of M-waves. Muscle strength was evaluated from the root mean square (RMS; Tests A and B) and peak to peak (PP; Test C) values obtained from the sEMG data. Measures related to amplitude (RMSa; RMSm; RMSa; PP) were normalised with their pre-training values for every muscle prior to statistical analysis, leading to values as a proportion of the initial value. The evaluation of muscle fatigue was performed using a Fourier test analysis of the frequency range, obtaining the median frequency (MF) for all tests. Muscle thickness (MT) was measured by ultrasound of left and right sides of the rectus abdominis. Data were analysed using non parametric test of Wilcoxon (Test A RMSa; Test A RMSm; Test B RMSa; Test B RMSm; Test C PP; MT; P<0.05) and t-test (Test A MF; Test B MF; Test C MF; P<0.05). Statistical differences were observed between baseline and trained horses. Muscle force increase following NMES training in Test B (RMSa 2.50±0.69; RMSm 2.59±0.76) and Test C (PP 5.20±1.76). Fatigue of the rectus abdominis decreased in Test A (168.33±55.19 vs 232.63±44.15 Hz) and Test C MF (187.93±20.76 vs 236.98±52.39 Hz), but not in Test B (363.98±45.48 vs 327.95±50.84 Hz). The difference in muscle thickness between the two groups was not significant (10.96±0.64; 11.78±0.79 mm). The results suggest that NMES training could be used as an effective method to increase muscle force and fatigue resistance of the rectus abdominis muscle in the horse.Depto. de Medicina y Cirugía AnimalFac. de VeterinariaTRUEpu

Response to Infliximab in Crohn’s Disease: Genetic Analysis Supporting Expression Profile

Substantial proportion of Crohn’s disease (CD) patients shows no response or a limited response to treatment with infliximab (IFX) and to identify biomarkers of response would be of great clinical and economic benefit. The expression profile of five genes (S100A8-S100A9, G0S2, TNFAIP6, and IL11) reportedly predicted response to IFX and we aimed at investigating their etiologic role through genetic association analysis. Patients with active CD (350) who received at least three induction doses of IFX were included and classified according to IFX response. A tagging strategy was used to select genetic polymorphisms that cover the variability present in the chromosomal regions encoding the identified genes with altered expression. Following genotyping, differences between responders and nonresponders to IFX were observed in haplotypes of the studied regions: S100A8-S100A9 (rs11205276*G/rs3014866*C/rs724781*C/rs3006488*A; P=0.05); G0S2 (rs4844486*A/rs1473683*T; P=0.15); TNFAIP6 (rs11677200*C/rs2342910*A/rs3755480*G/rs10432475*A; P=0.10); and IL11 (rs1126760*C/rs1042506*G; P=0.07). These differences were amplified in patients with colonic and ileocolonic location for all but the TNFAIP6 haplotype, which evidenced significant difference in ileal CD patients. Our results support the role of the reported expression signature as predictive of anti-TNF outcome in CD patients and suggest an etiological role of those top-five genes in the IFX response pathway