Effects of probiotics administration on lactose intolerance in adulthood: A meta-analysis.

This meta-analysis aimed to investigate the effect of probiotic administration on adults with lactose intolerance. Twelve studies were identified from databases such as PubMed, Cochrane Library, and Web of Knowledge based on the inclusion and exclusion criteria. The effect size was estimated using the standardized mean difference (SMD), and Cochrane's Q test was used to evaluate the statistical heterogeneity of the effect size. Moderator analysis, including meta-ANOVA and meta-regression, were performed to determine the cause of heterogeneity in the effect size using a mixed-effect model. Egger's linear regression test was conducted to evaluate publication bias. The results showed that probiotic administration alleviated the symptoms of lactose intolerance, including abdominal pain, diarrhea, and flatulence. Among them, the area under the curve (AUC) showed the greatest decrease following probiotic administration (SMD, -4.96; 95% confidence interval, -6.92 to -3.00). In the meta-ANOVA test, abdominal pain and total symptoms decreased with monostrain probiotic administration. This combination was also effective for flatulence. The dosage of probiotics or lactose was significantly associated with a reduction in the total symptom score, and the linear regression models between the dosage and SMD were found to be Y = 2.3342 × dosage - 25.0400 (R2 = 79.68%) and Y = 0.2345 × dosage - 7.6618 (R2 = 34.03%), respectively. Publication bias was detected for most items. However, even after effect size correction, the probiotic administration effect for all items remained valid. The administration of probiotics was effective at improving adult lactose intolerance, and it is expected that the results of this study could help improve the nutritional status of adults by increasing their consumption of milk and dairy products in the future.

A composite scale to recognize abdominal pain and its variation over time in response to analgesia in rabbits.

OBJECTIVE: To refine a composite scale for pain evaluation in rabbits and evaluate it for pain variations over time. To determine the differences between objective-Centro Animali Non Convenzionali Rabbit Scale (CANCRS) and subjective-Visual Analogue Scale (VAS) in assessing abdominal pain. STUDY DESIGN: Observational case-control study. ANIMALS: A total of 86 rabbits, 47 healthy animals and 39 animals with gastrointestinal stasis syndrome (RGIS), participated in the study; of 39 animals with RGIS, 32 animals participated in the second part of the study. METHODS: In part 1, rabbits underwent pain assessments with VAS and CANCRS. In part 2, the animals underwent four pain assessments with three CANCRS. The first assessment was performed prior to pain management, the others after 30, 60 and 90 minutes. Statistics included Mann-Whitney U test for in-between group comparisons and analysis of variance to assess differences over time. Sensitivity and specificity for each variable of CANCRS were calculated to obtain weighting factors. RESULTS: CANCRS showed differences between healthy and diseased rabbits (p = 0.0001), and median scores were 5 [interquartile range (IQR): 4-6) and 9 (IQR: 7-11), respectively. VAS showed differences between healthy and diseased rabbits (p = 0.02), and median scores were 4 (IQR: 2-5.35) and 5.3 (IQR: 2.65-6.45), respectively. The cut-off scores for CANCRS and VAS for differentiation between healthy and diseased rabbits were 7 (specificity 89%, sensitivity 79%) and 4.4 (specificity 59%, sensitivity 69%), respectively. Internal validity testing of CANCRS was significant at each time point. CONCLUSIONS AND CLINICAL RELEVANCE: Some variables should be excluded from CANCRS when assessing abdominal pain. CANCRS performed better than VAS, and it detected variations in pain in response to analgesia.

An atypical presentation of a mesenteric Meckel's diverticulum in a 7-year-old warmblood mare: case report.

BACKGROUND: Meckel's diverticula are a rare cause of small intestinal strangulation, diagnosed at laparotomy or necropsy. This congenital anomaly of the gastrointestinal tract originates from a remnant of the vitelline duct. In reported equine cases, they present as a full-thickness diverticulum on the antimesenteric border of the distal jejunum or proximal ileum. CASE PRESENTATION: On laparotomy a Meckel's diverticulum positioned at the mesenteric side was found to be the cause of small intestinal strangulation. This position is very uncommon and to the best knowledge of the authors there is no unambiguous description of another case. CONCLUSIONS: Meckel's diverticula should be on the list of differential diagnoses in cases of small intestinal strangulation. As in humans, equine Meckel's diverticula can have the standard antimesenteric as well as a more exceptional mesenteric location. This case adds to the series of anecdotal reports of anomalies with regard to Meckel's diverticula in the horse.

Evaluation of peritoneal l-lactate concentration in horses in the early post-partum period.

BACKGROUND: Peritoneal fluid lactate concentration is an important diagnostic tool in horses with abdominal pain. Information on peritoneal lactate concentrations is lacking following parturition in the mare. OBJECTIVES: To compare blood and peritoneal lactate concentrations in a population of mares within 36 h post-partum, report a normal reference range and identify any impact of retained foetal membranes (RFMs). METHODS: This is a retrospective study evaluating healthy mares from which blood and peritoneal samples had been obtained within 36 h of parturition. Exclusion criteria included signs of abdominal pain within this period. Data was interrogated for normality using a Shapiro-Wilk test. Wilcoxon signed-rank test and Bland-Altman analysis were used to compare blood and peritoneal lactate concentrations. Linear regression was used to compare age and breed data with peritoneal lactate concentrations. Significance was defined as p < 0.05. RESULTS: Forty mares met the inclusion criteria. Mean age was 12.6 ± 4.1 years, and most mares were multiparous (65%). Peritoneal lactate ((1.2 (IQR = 0.9-1.6) mmol/L) was increased compared to blood lactate concentration (0.7 (IQR = 0-1.1)mmol/L; p < 0.001). Plasma total protein (TP) concentrations were 68 (IQR = 64-74) g/L and peritoneal protein concentrations 8 (IQR = 4-9.7) g/L. Six mares developed RFM. The median fold-increase in peritoneal lactate concentration compared to blood lactate concentration was 0.9 (IQR: 0.01-1.7; range: 0-2.5). The reference range for peritoneal fluid lactate concentration was 0-2.5 mmol/L. CONCLUSION: Peritoneal lactate concentrations in healthy post-partum mares remained within the normal reference range and were not influenced by RFM or parturition. Increased peritoneal lactate in this group warrants further investigation.

Evaluation of substance P as a biomarker for pain in equine colic.

Equine colic is an important condition associated with acute abdominal pain and one of the leading causes of death in horses. As such, objectively evaluating pain is of interest for attending veterinarians. Pain scales for assessment are present, but no single pain-specific biomarker has been reported. The aim of this study was to determine if substance P (SP) could be a reliable biomarker to reflect pain and serve as a parameter to predict outcome in equine colic. The hypothesis was that horses displaying severe colic signs present with higher values of SP in contrast to those with mild colic signs. Thirty warmblood horses, aged between 3 and 20 years were recruited; evenly distributed (10 horses each) in three colic groups (mild, moderate, severe). To classify the colic signs, the horses were graded by the Equine Acute Abdominal Pain Scale (EAAPS). Clinical examination and EAAPS were performed at arrival in the hospital. Blood samples were collected four times in hourly intervals commencing from arrival. For comparison, already established parameters for prognosticating equine colic (heart rate, serum cortisol, and blood lactate concentration) were also measured. The assumption of increasing SP concentrations along with pain could not be confirmed. SP did not show any association with heart rate, cortisol, lactate, or EAAPS. Whereas the established parameters increased according to the EAAPS, SP remained stable in individual horses regardless of clinical signs, treatment, and disease progression. Consequently, SP was not a reliable parameter to reflect painful conditions or to predict outcome in equine colic.

Postsurgical segmental mesenteric ischemic thrombosis in a horse.

A 16-year-old, Lusitanian stallion was admitted to the Veterinary Teaching Hospital with a 12-hour history of signs of abdominal pain. Exploratory celiotomy was performed due to an inguinal hernia, and a second celiotomy was performed in response to the abdominal pain. The horse was euthanized and mesenteric venous thrombosis was diagnosed and considered likely due to peritonitis and systemic inflammatory response syndrome (SIRS).

Thrombose ischémique mésentérique segmentaire post-chirurgicale chez un cheval. Un étalon Lusitanien âgé de 16 ans a été admis à l'hôpital d'enseignement vétérinaire avec une anamnèse de 12 heures de douleurs abdominales. Une coeliotomie exploratoire a été réalisée en raison d'une hernie inguinale et une deuxième coeliotomie a été réalisée en réponse à la douleur abdominale. Le cheval a été euthanasié et une thrombose de la veine mésentérique a été diagnostiquée et considérée probablement attribuable à une péritonite et au syndrome de la réaction inflammatoire systémique (SRIS).(Traduit par Isabelle Vallières).

Gastrojejunostomy as a treatment for gastric outflow disorders in four adult horses.

Four adult horses with histories of moderate abdominal pain and inappetence were diagnosed with delayed gastric emptying and gastric impaction attributed to pyloroduodenal obstruction (three cases) or duodenitis (one case). A stapled side-to-side gastrojejunostomy was performed on all horses. Two horses returned to work and survived ≥3 years. One horse was euthanased 6 months post-surgery due to recurrent abdominal pain, and one was found dead 5 months postsurgery after an unattended foaling.

Lymphomatosis as a Cause of Abdominal Pain and Distension in Two Adult Horses.

Two equine patients presented separately with severe abdominal distention, colic, lethargy, and decreased appetite. An ante-mortem diagnosis of lymphoma was reached in each case based on peritoneal fluid cytology. Due to a poor prognosis, the horses were humanely euthanized. Post-mortem examination with histology and immunohistochemistry confirmed both cases as lymphoma: alimentary B-cell lymphoma of the distal jejunum and cecum in one case, and T-cell lymphoma of the cecum in the second case. Both cases exhibited extensive metastasis with peritoneal and pleural serosae covered in small nodules and plaque like masses consistent with lymphomatosis. These cases document a unique presentation of lymphoma in equine patients presenting as peritoneal lymphomatosis with ascites.

Ultrasound-guided percutaneous antegrade pyelography with computed tomography for the diagnosis of spontaneous partial ureteral rupture in a dog.

A 10-year-old spayed female dalmatian dog developed acute vomiting and abdominal pain. Ultrasound examination of the abdomen showed right hydronephrosis and proximal ureter dilation with mild retroperitoneal free fluid. Computed tomography (CT) of the abdomen confirmed the ultrasonographic findings and revealed, additionally, a right ureteral stone. Spontaneus rupture of the right ureter was confirmed with CT post ultrasound-guided percutaneous antegrade pyelography. Pyeloureteral rupture and the presence of a ureteral stone were confirmed at surgery.

Pyélographie antégrade percutanée guidée par échographie avec tomodensitométrie pour le diagnostic d'une rupture urétrale partielle spontanée chez un chien. Une chienne Dalmatien stérilisée âgée de 10 ans a manifesté des vomissements et de la douleur abdominale aigus. Une échographie de l'abdomen a montré de l'hydronéphrose à droite et une dilatation proximale de l'urètre avec un peu de liquide rétropéritonéal libre. Une tomodensitométrie de l'abdomen a confirmé les résultats de l'échographie et a révélé, en plus, un calcul urétéral droit. Une rupture spontanée de l'urètre droit a été confirmée par tomodensitométrie après une pyélographie antégrade percutanée guidée par échographie. La rupture pyélo-urétérale et la présence de calcul urétéral ont été confirmées à la chirurgie.(Traduit par Isabelle Vallières).

Long-term follow-up of a juvenile simple renal cyst in a dog treated by laparoscopic deroofing, fulguration, and omentalization.

CASE DESCRIPTION: A 10-month-old male crossbred dog presented with a 4-week history of polyuria and polydipsia and a 6-month history of vomiting. CLINICAL FINDINGS: Clinical examination revealed abdominal pain and right-sided nephromegaly. Biochemistry was within normal limits. Diagnostic imaging showed a well-defined, unilateral renal mass containing anechoic fluid consistent with a simple renal cyst (SRC). TREATMENT AND OUTCOME: The cyst was drained under ultrasonographic guidance but recurred 3 months later, concomitant with recurrence of the previously reported clinical signs. The cyst was then deroofed, fulgurated, and omentalized under laparoscopy by use of a 3-port technique. The resected cystic wall was histopathologically consistent with an SRC, presumptively congenital. The dog showed a good recovery with resolution of clinical signs. Renal function was normal at last follow-up, conducted 2 years postoperatively, without evidence of recurrent disease. CLINICAL RELEVANCE: To our knowledge, this was the first report of a symptomatic juvenile SRC of presumptively congenital origin in a dog treated successfully by laparoscopic deroofing, fulguration, and omentalization. The polyuria, polydipsia, chronic vomiting, and abdominal pain may all have been related to space-occupying effects of the cyst, as these symptoms resolved post-treatment. Results of long-term follow-up advocate for this durable cure of SRC by use of laparoscopic procedures, especially when compared to simple drainage of the cyst, as the latter initially failed in the present case.

Risk factors for incisional complications after exploratory celiotomy in horses: do skin staples increase the risk?

OBJECTIVE: To assess risk factors for celiotomy incisional infection in horses, especially the use of staples for skin closure. STUDY DESIGN: Case series. ANIMALS: Horses (n=356) that had 1 exploratory celiotomy for colic and survived >2 weeks after surgery between March 1, 2004 and December 31, 2007. METHODS: Incisions were classified as "normal" (no complication, only edema, serous drainage lasting <24 hours) or as "surgical site infection (SSI)" (persistent serosanguinous drainage or purulent drainage with or without positive bacterial culture). All possible risk factors, including method of skin closure (monofilament sutures or staples), were statistically analyzed using univariate and multivariate logistic regression. RESULTS: Of 356 horses, 303 (85%) had normal wound healing and 53 (15%) developed a SSI (purulent: 48 [14%]; persistent serosanguinous: 5 [1%]). Bacterial cultures were positive in 33 of 40 cases. Factors significantly associated with SSI in the multivariate analysis were: use of staples for skin closure (odds ratio [OR] 3.85, P<.001) and surgical site closure by a 1st or 2nd year resident (OR 2.20, P=.016). Lavage of the linea alba with sterile saline solution after closure was a protective factor (OR 0.38, P=.004). CONCLUSION: Use of staples for skin closure and less experienced surgeons closing the abdomen are risk factors for incisional infection. Incisional lavage after linea alba closure was a protective factor. CLINICAL RELEVANCE: Despite their ease and speed of application, skin staples can lead to an increase in celiotomy wound complications in horses.

Indicators of 'critical' outcomes in 941 horses seen 'out-of-hours' for colic.

BACKGROUND: This study aimed to describe the presentation and outcomes of horses with signs of colic (abdominal pain) seen 'out-of-hours' in equine practice. METHODS: This was a retrospective study of horses seen 'out-of-hours' with colic by two equine veterinary practices between 2011 and 2013. Case outcomes were categorised as 'critical' or 'not critical'. A critical outcome was defined as requiring medical or surgical hospital treatment, or resulting in euthanasia or death. A non-critical outcome was defined as resolving with simple medical treatment. A hierarchical generalised linear model was used to identify 'red flag' parameters (aspects of signalment, history and presenting clinical signs) associated with critical outcomes. RESULTS: Data were retrieved from 941 cases that presented with colic; 23.9 per cent (n=225/941) were critical. Variables significantly associated with the likelihood of a critical outcome in the final multivariable model were increased heart rate (P<0.001), age of the horse (P=0.013) and abnormal mucous membrane colour (P<0.001). Overall 18 per cent (n=168/941) of cases were euthanased. CONCLUSIONS: This study highlights the mortality associated with colic. The 'red flag' parameters identified should be considered an essential component of the primary assessment of horses with colic.

Validation of the Unesp-Botucatu composite scale to assess acute postoperative abdominal pain in sheep (USAPS).

A scale with robust statistical validation is essential to diagnose pain and improve decision making for analgesia. This blind, randomised, prospective and opportunist study aimed to develop an ethogram to evaluate behaviour and validate a scale to assess acute ovine postoperative pain. Elective laparoscopy was performed in 48 healthy sheep, filmed at one preoperative and three postoperative moments, before and after rescue analgesia and 24 hours after. The videos were randomised and assessed twice by four evaluators, with a one-month interval between evaluations. Statistical analysis was performed using R software and differences were considered significant when p <0.05. Based on the multiple association, a unidimensional scale was adopted. The intra- and inter-observer reliability ranged from moderate to very good (intraclass correlation coefficient ≥ 0.53). The scale presented Spearman correlations > 0.80 with the numerical, simple descriptive, and visual analogue scales, and a correlation of 0.48 with the facial expression scale. According to the mixed linear model, the scale was responsive, due to the increase and decrease in pain scores of all items after surgery and analgesic intervention, respectively. All items on the scale demonstrated an acceptable Spearman item-total correlation (0.56-0.76), except for appetite (0.25). The internal consistency was excellent (Cronbach's α = 0.81) and all items presented specificity > 0.72 and sensitivity between 0.61-0.90, except for appetite. According to the Youden index, the cut-off point was ≥ 4 out of 12, with a diagnostic uncertainty zone of 4 to 5. The area under the curve > 0.95 demonstrated the excellent discriminatory capacity of the instrument. In conclusion, the Unesp-Botucatu pain scale in sheep submitted to laparoscopy is valid, reliable, specific, sensitive, with excellent internal consistency, accuracy, discriminatory capacity, and a defined cut-off point.

Centrally administered verapamil prevents the autonomic reaction to visceral pain in sheep.

The significant role of voltage gated calcium channels (VGCC) L-type antagonists used concomitantly with opioids in attenuation of clinical pain has been confirmed. The aim of this study was to evaluate the effect of centrally administered verapamil on behavior and biochemical parameters in sheep that have undergone experimental duodenal distension (DD) and to determine whether verapamil exerts any anti-nociceptive effects under these conditions. The study was carried out using 24 mature crossbred ewes, each weighing 38-43 kg. Verapamil, a VGCC blocker, was administered through an intracerebroventricular cannula at the following doses: 0.25, 0.5, 1.0 and 2.0mg in toto. Ten minutes later experimental DD was conducted by insertion and the distension of rubber balloon (containing 40 ml of warm water) inserted into sheep duodenum. After 5 min of mechanical DD the following reactions were then observed: the significant increase in behavioral pain responses, i.e. tachycardia, hyperventilation, inhibition of reticulo-ruminal contractions (70% approximately, during 15 min), an increase of plasma catecholamine concentration (over 7-fold increase of epinephrine during 2h following DD, 2-times norepinephrine and +/-80% increase of dopamine). Verapamil infusion administered 10 min prior to DD decreased intensity of visceral pain responses, such as: behavioral changes, tachycardia, hyperventilation, inhibition of the reticulo-rumen motility and efficiently prevented the appearance of catecholamine release. These data demonstrated that the development and persistence of duodenal hyperalgesia depends on the activation of Ca(2+) ion flux leading to neurotransmitters release and modulation of membrane excitability. The observed antinociceptive action of VGCCs type-L blockers suggests that these channels play a crucial role in the modulation of acute visceral hyperalgesia in sheep.

The inhibition of experimentally induced visceral hyperalgesia by nifedipine - a voltage-gated Ca(2+) channels blocker (VGCCs) in sheep.

Present study examined the effect of VGCC L-type blocker - nifedipine given i.c.v. (0.25, 0.5, 1 and/or 2mg in toto) on the development of nociceptive behavior, clinical symptoms, plasma catecholamin concentration and reticulo-rumen motility following 5 min lasting mechanical duodenal distension (DD) in sheep. After 24h of fasting, all animals received i.m. ketamine analgesia (20 mg kg(-1)B.W) and anesthetized with pentobarbital (20 mg kg(-1)B.W., i.v. infusion) The permanent stainless steel cannula 29 mm in length and 2mm in diameter was inserted into the lateral cerebral ventricle (controlled by cerebro-spinal efflux) 10mm above the bregma and 5mm laterally from the midline sutures using stereotaxic method. Under the same general anesthesia/analgesia a T-shaped silicon cannula (inside diameter of 21 mm), was inserted into the duodenum (12 cm from pylorus). Second identical cannule was inserted into the dorsal sac of the rumen, a previously described. After surgery each animal was kept in individual boxes for 10 days prior to experiment and was treated i.m. with benzyl procaine penicillin 30,000 I.U kg(-1)B.W.)+dihydrostreptomycine sulfate (10 g kg(-1)B.W.)+prednisolone acetate (1.2 mg kg(-1)B.W.) combination and i.m. ketamine (20 mg kg(-1)B.W.) every day by seven consecutive days. Experimental DD was conducted by insertion and then distension of rubber balloon (containing 40 ml of warm water) inserted into sheep duodenum. Duodenal distension produced a significant increase in behavioral pain manifestations, tachycardia, hyperventilation, inhibition of reticulo-ruminal contractions rate (from 87.2 to 38.0% during 15-20 min), an increase of plasma catecholamine concentration (over 6.4-fold increase of epinephrine during 2h following DD, 2-times norepinephrine and 84% increase of dopamine). Nifedipine infusion administered 10 min prior to DD decreased intensity of visceral pain manifestations such as: behavioral changes, hyperventilation, reticulo-rumen motility and efficiently prevent appearance of catecholamine release. These data demonstrated that the development and persistence of duodenal hyperalgesia depends on the activation of Ca(2+) ion flux leading to neurotransmitters release and modulation of membrane excitability. It seems that nifedipine given i.c.v. 10 min prior to DD (as a source of visceral pain), inhibited specific receptors 1 subunits of VGCCs in target tissues, prevented depolarization of cell membranes and release of neurotransmitters responsible for pain sensitivity in sheep. The observed antinociceptive action of VGCCs type L blockers suggest that these channels play a crucial role in the modulation of acute visceral hyperalgesia in sheep.

What is your diagnosis? Intra-abdominal mass aspirate from a spayed dog with abdominal pain.

An 8-year-old, spayed female Labrador Retriever was presented for evaluation of unwillingness to exercise. On clinical examination abdominal pain was elicited, and a midabdominal mass was detected in survey radiographs. Ultrasound-guided fine-needle aspiration of the intra-abdominal mass was done. The cytologic findings indicated chronic granulomatous inflammation with reactive fibroplasia, cholesterol crystals, and extracellular foreign material. The foreign material consisted of opaque, basophilic fragments of uniform width (5-10 mum) and variable length (30-180 microm) and was observed extracellularly and within macrophages. The material was birefringent under polarized light. Histologic examination of the excised mass confirmed the cytologic findings and a diagnosis of gossypiboma (textiloma) was made, consistent with retention of a surgical sponge. This case provides a unique example of the utility of fine-needle aspiration for the diagnosis of gossypiboma.

Risk factors for acute abdominal pain (colic) in the adult horse: A scoping review of risk factors, and a systematic review of the effect of management-related changes.

Acute abdominal pain (colic) is the most common reason for emergency veterinary treatment in the horse. Consolidation of data through a systematic review is important to inform evidence-based medicine and clinical guidelines, but there are currently no published systematic reviews on colic in the horse. The aim of this study was to identify, categorize and appraise the evidence on factors associated with increased risk of developing abdominal pain (colic) due to gastrointestinal disease in the adult horse. A scoping review was performed to identify and categorize evidence on all risk factors for colic. A systematic review of management-related risk factors was then performed following PRISMA guidelines. Both searches were conducted in Medline, CAB Abstracts and Web of Science databases, and publications were assessed against inclusion and exclusion criteria. For the scoping review, study and participant characteristics of included publications and key results were extracted and tabulated. For the systematic review, cohort, case-control or cross-sectional studies investigating acute abdominal pain in horses within two weeks of management changes were assessed. Study characteristics, participant characteristics and study results of included publications for the systematic review were extracted and tabulated. Included publications were appraised using the Joanna Briggs Institute Critical Appraisal Tools for cohort, case-control and cross-sectional studies. The scoping review search identified 3,756 publications. Fifty eight studies met final inclusion criteria, and 22 categories of risk factors were identified. These were grouped into three broad areas: horse-related factors, management-related factors and environment-related factors. The largest body of evidence related to management change. The systematic review of management change identified 410 publications: 14 met inclusion criteria for analysis. These consisted of one cohort, eight case-control and five cross-sectional studies. The studies were conducted between 1990-2008, and the majority of studies were located in the USA (8/14) or UK (3/14). The risk factors related to management change that were assessed were feed, carer, exercise, pasture, water and housing. The largest bodies of evidence for increased risk of colic associated with management change were changes in feed (5/14 publications) and recent change in housing (3/14). Most studies (8/14) did not meet the JBI criterion on confounding factors. There was marked heterogeneity of study methodologies and measures. This is the first study to use a combined scoping and systematic review to analyse evidence for modifiable risk factors for a common condition in the horse. It provides a comprehensive review that will be a key resource for researchers, veterinary practitioners and horse owners. It identified modifiable risk factors associated with an increased risk of colic which should be a key target for preventative health programmes. The findings from the critical appraisal were used to develop recommendations for future research to improve the quality of evidence-based veterinary medicine.