Judit Viu

Acid-base imbalances during a 120 km endurance race compared by traditional and simplified strong ion difference methods.

REASONS FOR PERFORMING STUDY Acid-base disturbances are traditionally assessed using the Henderson-Hasselbach equation. The simplified strong ion approach describes more accurately the complex acid-base and electrolyte abnormalities present in endurance horses. OBJECTIVE To describe acid-base and electrolytes changes in fit horses competing in a FEI*** 120 km endurance race and to compare the traditional vs. strong ion approaches. METHODS Thirty horses were initially enrolled in the study. Venous blood samples were obtained before the race (n = 25), at the second (n = 29; 65.4 km) and third vet-gates (n = 23, 97.4 km) and upon race completion (n = 17). Blood gas analysis was performed to determine pH, PCO(2), PO(2), Na(+), K(+) and iCa(++), and calculate HCO(3)(-), base excess and tCO(2). Packed cell volume and total protein, globulin, albumin, lactate, phosphate, glucose and creatinine concentrations, as well as muscle enzymes activities, were also determined. Calculated variables included strong ion difference (SIDm), strong ion gap (SIG) and nonvolatile buffer concentration (A(tot)). A longitudinal linear model using the general estimating equation methodology was used for statistical analysis. RESULTS Mild but significant increases in PCO(2), SIDm, lactate, plasma protein, globulins and A(tot), as well as a decrease in potassium concentrations were observed from the second vet-gate to race finish when compared to prerace values (P < 0.05). Using the strong ion approach, 67% samples showed acid-base disturbances vs. 70% when using the traditional method, but their interpretations only matched in 24% of measurements. CONCLUSIONS A complex acid-base imbalance characterised by a mild strong ion alkalosis (hypochloraemia attenuated by hyperlactataemia), nonvolatile buffer acidosis and compensatory mild respiratory acidosis were present in most horses, although pH did not significantly change during a 120 km endurance race. The strong ion approach to interpretation of acid-base balance should be favoured over the traditional approach in endurance horses, given the frequent and complex alterations in PCO(2), SIDm and A(tot) during a race.

Metabolic and Endocrine Profiles in Sick Neonatal Foals Are Related to Survival

BACKGROUND Sick neonatal foals suffer from a variety of endocrine and metabolic derangements that may be related to outcome. There are several hepatic and lipid metabolism blood markers that have never been assessed in neonatal foals. OBJECTIVES Assess panel of endocrine and metabolic variables in group of sick and healthy neonatal foals in order to describe their relationship with diagnosis and survival. ANIMALS All neonatal foals referred to Unitat Equina-Fundació Hospital Clínic Veterinari during 3 consecutive foaling seasons and a group of healthy foals. METHODS Observational prospective study. Blood samples were obtained on admission and, when possible, after 24-48 h of hospitalization and immediately before discharge or death. Measured variables were triglycerides, nonsterified fatty acids, glucose, creatinine, urea, γ-glutamyltransferase, glutamate dehydrogenase (GLDH), insulin, cortisol, bile acids, and adrenocorticotropic hormone (ACTH). ACTH/cortisol and glucose/insulin ratios were calculated. RESULTS Urea, creatinine, and cortisol had median concentrations in septic and nonseptic foals 2- to 8-fold higher than in the control group (P < .001). Median ACTH concentration in the septic group was approximately 4 times higher than in nonseptic and control foals (P < .001). ACTH/cortisol ratio was significantly lower in sick foals compared to control foals (P < .001). A score was designed including creatinine, GLDH, and cortisol. When ≥ 2 of these variables were altered (P < .001), the foal had 32 times more risk of dying (OR, 31.7; 95% CI, 7.7-130.3). CONCLUSIONS AND CLINICAL IMPORTANCE Plasma creatinine, GLDH, and cortisol should be determined in sick newborn foals on admission because of their association with survival.

Immunohistochemical evaluation of tissue factor, fibrin/fibrinogen and D-dimers in canine gliomas

In human gliomas, tissue factor (TF) is overexpressed, associated with the grade of malignancy and influences tumour biology. Intra-tumoural fibrin/fibrinogen deposition and activation of the fibrinolytic system also play a role in tumour cell proliferation and angiogenesis. The first aim of the present study was to investigate TF expression and the presence of fibrin/fibrinogen and D-dimers in canine glioma biopsies, graded according to the World Health Organization (WHO) classification of tumours of the central nervous system. The second aim was to investigate the occurrence of intravascular thrombosis (IVT) in canine gliomas, as a potential histological marker of glioma type or grade of malignancy. An immunohistochemical study using antibodies against TF, fibrin/fibrinogen and D-dimers was performed with 24 glioma samples, including 15 oligodendrogliomas, 6 astrocytomas and 3 mixed gliomas. Immunohistochemical data were statistically analysed to determine whether there was any relationship between glioma type and grade of malignancy. All gliomas were moderate to strongly positive for TF and the staining score was significantly higher (P = 0.04) in high-grade (III or IV) than in low-grade (II) gliomas. Intra-tumoural fibrin/fibrinogen deposition was detected in all tumour biopsies assessed, and D-dimers were detected in 17/24 gliomas. IVT was a frequent finding, but was not linked to a specific glioma type or malignancy grade. TF expression, fibrin/fibrinogen deposition, extravascular fibrinolytic system activation and IVT occur in canine gliomas. Canine glioma might be a suitable model for studying coagulation and fibrinolysis as potential therapeutic targets for human gliomas.

Fibrinolytic Activity in Cerebrospinal Fluid of Dogs with Different Neurological Disorders

BACKGROUND Fibrinolytic activity in cerebrospinal fluid (CSF) is activated in humans by different pathologic processes. OBJECTIVES To investigate fibrinolytic activity in the CSF of dogs with neurological disorders by measuring CSF D-dimer concentrations. ANIMALS One hundred and sixty-nine dogs with neurological disorders, 7 dogs with systemic inflammatory diseases without central nervous system involvement (SID), and 7 healthy Beagles were included in the study. Dogs with neurological disorders included 11 with steroid-responsive meningitis-arteritis (SRMA), 37 with other inflammatory neurological diseases (INF), 38 with neoplasia affecting the central nervous system (NEO), 28 with spinal compressive disorders (SCC), 15 with idiopathic epilepsy (IE), and 40 with noninflammatory neurological disorders (NON-INF). METHODS Prospective observational study. D-dimers and C-reactive protein (CRP) were simultaneously measured in paired CSF and blood samples. RESULTS D-dimers and CRP were detected in 79/183 (43%) and in 182/183 (99.5%) CSF samples, respectively. All dogs with IE, SID, and controls had undetectable concentrations of D-dimers in the CSF. CSF D-dimer concentrations were significantly (P < .001) higher in dogs with SRMA than in dogs with other diseases and controls. CSF CRP concentration in dogs with SRMA was significantly (P < .001) higher than in dogs of other groups and controls, except for the SID group. No correlation was found between blood and CSF D-dimer concentrations. CONCLUSIONS AND CLINICAL IMPORTANCE Intrathecal fibrinolytic activity seems to be activated in some canine neurological disorders, and it is high in severe meningeal inflammatory diseases. CSF D-dimer concentrations may be considered a diagnostic marker for SRMA.

Parallel testing of plasma iron and fibrinogen concentrations to detect systemic inflammation in hospitalized horses

Objectives To determine if plasma iron concentration is different between horses with and without systemic inflammation (SI) and to assess the accuracy for the detection of SI by assaying plasma iron and fibrinogen concentrations, individually or combined. To assess the prognostic value of plasma iron concentration and to describe the progression of plasma iron and fibrinogen concentrations during hospital follow-up, and its relation to SI and survival. Design Prospective observational study evaluating plasma iron and fibrinogen. Setting University veterinary teaching hospital. Animals Equine patients greater than 30 days of age. Interventions None. Measurements and Main Results Plasma iron and fibrinogen concentration was prospectively determined in hospitalized horses. Horses were classified into 2 groups: SI and non-SI. Horses were also classified according to clinical outcome. A group of control healthy horses was also included. A total of 135 horses were included in the study. Plasma iron concentration was significantly lower and fibrinogen concentration was higher in the SI group. Nonsurvivors had a mean plasma fibrinogen concentration significantly higher than survivors. The combination of plasma iron and fibrinogen has a high degree of specificity, sensitivity, and accuracy for the detection of SI in horses. Follow-up measurements were obtained in 48 horses. Surviving horses normalized plasma iron concentration during follow-up examination whereas nonsurviving horses had persistently low plasma iron concentrations. Conclusions Plasma iron concentration alone is an accurate marker of SI in hospitalized horses. Alteration of both plasma iron and fibrinogen concentrations improves the specificity and positive predictive value for diagnosis of SI. Alteration of either one of both increases sensitivity and negative predictive value. Surviving horses normalized plasma iron concentrations during follow-up period. The combination of plasma iron and fibrinogen concentrations may help in the detection of SI. Follow-up of plasma iron concentrations may provide useful prognostic information.OBJECTIVES To determine if plasma iron concentration is different between horses with and without systemic inflammation (SI) and to assess the accuracy for the detection of SI by assaying plasma iron and fibrinogen concentrations, individually or combined. To assess the prognostic value of plasma iron concentration and to describe the progression of plasma iron and fibrinogen concentrations during hospital follow-up, and its relation to SI and survival. DESIGN Prospective observational study evaluating plasma iron and fibrinogen. SETTING University veterinary teaching hospital. ANIMALS Equine patients greater than 30 days of age. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Plasma iron and fibrinogen concentration was prospectively determined in hospitalized horses. Horses were classified into 2 groups: SI and non-SI. Horses were also classified according to clinical outcome. A group of control healthy horses was also included. A total of 135 horses were included in the study. Plasma iron concentration was significantly lower and fibrinogen concentration was higher in the SI group. Nonsurvivors had a mean plasma fibrinogen concentration significantly higher than survivors. The combination of plasma iron and fibrinogen has a high degree of specificity, sensitivity, and accuracy for the detection of SI in horses. Follow-up measurements were obtained in 48 horses. Surviving horses normalized plasma iron concentration during follow-up examination whereas nonsurviving horses had persistently low plasma iron concentrations. CONCLUSIONS Plasma iron concentration alone is an accurate marker of SI in hospitalized horses. Alteration of both plasma iron and fibrinogen concentrations improves the specificity and positive predictive value for diagnosis of SI. Alteration of either one of both increases sensitivity and negative predictive value. Surviving horses normalized plasma iron concentrations during follow-up period. The combination of plasma iron and fibrinogen concentrations may help in the detection of SI. Follow-up of plasma iron concentrations may provide useful prognostic information.

Acid base imbalances in ill neonatal foals and their association with survival.

Reasons for performing study: Acid‐base imbalances observed in human paediatric patients are associated with outcome. Likewise, neonatal foals may have different acid‐base imbalances associated with diagnosis or prognosis. Objectives: To determine acid‐base imbalances by the quantitative method in ill neonatal foals and assess their association with diagnosis and prognosis. Study design: Observational prospective clinical study. Methods: This study included 65 ill neonatal foals (32 septic, 33 nonseptic) admitted to an equine referral hospital from 2005 to 2011with acid‐base parameters determined on admission and a control group of 33 healthy neonatal foals. Blood pH, pCO2, sodium, potassium, chloride, L‐lactate, albumin and phosphate concentrations were determined. Bicarbonate, globulin, measured strong ion difference (SIDm), nonvolatile weak buffer concentrations (Atot), base excess and its components were calculated. Analysis of covariance (ANCOVA) and multiple linear regression statistical analyses were performed. Results are summarised as mean ± s.d. for normally distributed variables and median [25–75th percentiles] for non‐normally distributed ones. Results: A total of 63% of ill foals had respiratory alkalosis and 58.5% had SIDm acidosis. The combination of both alterations was detected in 21 of 65 ill foals and abnormal pH was found in 24 of 65. Compared with healthy foals, ill foals had significantly lower SIDm (nonseptic 31.6 ± 6.3 [P<0.01] and septic 32.0 ± 6.4 [P<0.01] vs. control 40.3 ± 3.1 mmol/l), potassium (nonseptic 3.5 [3.3–3.8; P<0.01] and septic 3.6 [3.2–4.3; P = 0.01] vs. control 4.2 [3.8–4.5] mEq/l) and higher L‐lactate (nonseptic 5.1 ± 4.2 [P = 0.01] and septic 5.0 ± 3.7 [P = 0.03] vs. control 2.5 ± 1.3 mmol/l). Significantly higher L‐lactate and venous pCO2 were found in nonsurviving (6.4 ± 3.5 mmol/l [P = 0.04] and 51 ± 13 mmHg [P<0.01]) compared with surviving foals. Conclusions: The most common acid‐base imbalances observed in ill foals were respiratory alkalosis, SIDm acidosis or mixed respiratory alkalosis with strong ion acidosis. Increased venous pCO2 and blood L‐lactate concentration were associated with poor outcome.

Myelographic and low-field magnetic resonance imaging findings in dogs with presumptive acute hydrated non-compressive nucleus pulposus extrusion

MRI is considered gold standard for the diagnosis of presumptive acute hydrated non-compressive nucleus pulposus extrusions (AHNCNPE). This retrospective study describes the myelographic findings in dogs with AHNCNPE diagnosed by low-field MRI and their association with neurological grade, need of surgical decompression and outcome. Forty-two myelographies (21 dogs with presumptive AHNCNPE, 21 dogs with Hansen type I disc disease herniation) were blindly evaluated. Site of herniation, compression pattern, ratio of length of the lesion to length of the second lumbar vertebra (LL:L2) and degree of spinal cord compression (SCC) were measured on the myelographies of dogs with presumptive AHNCNPE and were compared with the corresponding MRI features. Percentage of extruded volume of nucleus pulposus (VNP) was calculated on MR images. Myelographic interobserver agreement for presumptive diagnosis of AHNCNPE was almost perfect (κ=0.8). Accuracy of myelography to detect site of herniation was 80.9 per cent and to identify extradural compression was 57.1 per cent. Mean SCC was 5.8±2.6 per cent for myelography and 6.6±3 per cent for MRI. Mean LL:L2 ratio was 1.7±0.9 for myelography and 1.2±0.8 for MRI. Mean percentage of extruded VNP was 40±14 per cent, and it was positively associated with neurological grade.

Magnetic Resonance Imaging of Bacterial Meningoencephalitis in a Foal

Magnetic resonance imaging (MRI) in equidae suffering meningoencephalitis (ME) has not been described. The objective of this paper is to describe brain MRI findings in a foal with bacterial ME. A five-month-old, 200 kg bwt Arabian filly was referred with a history of abnormal mental status and locomotion. The filly was recumbent and obtunded, and pupillary light reflexes were sluggish, and oculocephalic movements were normally present. Ophthalmic examination revealed bilateral optic neuritis. Hematology revealed leukocytosis and neutrophilia. Cerebrospinal fluid analysis showed neutrophilic pleocytosis with intracellular bacteria. On brain MRI, there were multifocal cortical areas of mild hyperintensity on T2-weighted images (T2WI) affecting both hemispheres. The lesions had ill-delineated margins, and there was loss of differentiation between gray and white matter. Diffuse hyperintensity was also identified in the left cerebellar cortex on T2WI. Neither mass effect nor cerebral midline shift were identified. On FLAIR images, the lesions were also hyperintense and, in some areas, they seemed to coalescence to form diffuse cortical areas of hyperintensity. The MRI findings described were similar to the MRI features described in cases of humans and small animals with ME. Brain MRI can be a useful diagnostic tool in foals and small-sized equidae with intracranial disease.

Cranioencephalic Malformation with Atlanto-Occipital Luxation in an Andalusian Neonate Foal

A 45-kg, 12-hour-old Andalusian colt was referred to the Equine Teaching Hospital of Barcelona for evaluation of abnormal mental status and weakness with inability to stand from birth. Foaling was attended and reported to be uneventful. On physical examination, the foal was recumbent and showed signs of immaturity (eg, domed forehead and flexor tendon laxity of all 4 limbs), as well as an abnormal skull characterized by a prominent occipital crest on palpation. On neurological examination, the colt was stuporous, suckle reflex was absent, and pupilary reflex of the left eye was slow and incomplete (pupilary reflex of the right eye could not be assessed because of hyphema). Oculocephalic movements were normal. The foal had tachypnea (80 breaths/ min) with apneic periods induced by cervical manipulation, which made assisted ventilation necessary during examination. The foal’s heart rate was within normal limits (80 beats/min), but it had a weak arterial pulse, congested mucous membranes, and prolonged capillary refill time (3 seconds). All of these later signs were consistent with mild dehydration. Gastrointestinal sounds were absent and meconium impaction was detected on digital rectal palpation. Hematology and plasma biochemistry performed upon admission disclosed mildly increased lactate concentration (4.5mmol/L; reference range, o2.5mmol/L), PCV (55%; reference range, 40– 52%), total protein concentration (6 g/dL; reference range, 4.5–4.7 g/dL), PvCO2 (60mmHg; reference range, 37–43mmHg) and bicarbonate (26.6mEq/L; reference results, 23mEq/L), and decreased glucose (2mmol/L; reference range, 6–12.5mmol/L) and potassium (2.9mmol/L; reference range, 3.5–5.5mmol/L) concentrations, which was interpreted as a mixed acidemia because of respiratory and metabolic lactic acidosis. Septic score was 12 (normal index,o11). A cranio-cervical radiological study was performed. Images in stress position could not be taken because the foal showed apneic periods during vertical mobilization of the neck. The skull and cranial cervical vertebrae evidenced a domed forehead, occipital crest enlargement, no articulation between occipital and atlas bones, and hypoplasic occipital condyles (Fig 1). A definitive diagnosis of malformation of the caudal cranium and atlanto-occipital luxation was reached. Because of the poor prognosis, the colt was euthanized. Cranio-cervical radiographs in full flexion and extension, as well as collection of cerebrospinal fluid (CSF) from the atlanto-occipital space, were performed immediately after euthanasia. Cytological examination and lactate determination, as well as total protein concentration and creatine kinase activity, were performed. The liquid was clear but xanthochromic, had normal nucleated cell count and total protein concentration (117mg/ dL, reference range 99–120mg/dL), but creatine kinase activity and lactate concentration were increased (14 IU/ L, reference range 0–8 IU/L, and 4.4mmol/L, reference value o4mmol/L, respectively). Postmortem myelography also was performed by injecting 25mL of contrast (sodium amidotrizoate and meglumine amidotrizoate in a proportion of 10 : 66 in aqueous solution) in the atlanto-occipital space. Myelography in flexed-stressed position showed a 50% reduction of the subarachnoid space at the atlantooccipital junction as well as mild spinal cord compression between the 3rd and 4th cervical vertebrae because of dynamic subluxation (Fig 2A and B). At necropsy, a skull malformation was confirmed. The cranial dome was figure 8-shaped and the occipital crest was enlarged. There was caudalization of the hindbrain toward the foramen magnum. The medulla oblongata was situated between the occipital condyles, and the 4th ventricle could be seen through the foramen magnum (Fig 3). The cerebellar vermis had an S-shaped form due both to the pressure of adjacent bony structures and to the presence of hydrocephalus. In addition, there was an apparent vascular proliferation on the brain surface. Blood vessels were congested and associated with hemorrhages in the falciform and tentorium ligaments, and diffusely on the subarachnoid space. All of the ventricular system was enlarged without the presence of cellular debris in its lumen. Histological examination of the brain was performed. Hematoxylin-eosin, immunoperoxidase, and glial fibrillary acidic protein stains were used. Microscopically, the From the Servei de Medicina Interna Equina (Viu, Armengou, Jose-Cunilleras, Cesarini, Monreal) and the Unitat de Neuropatologia Veterinària (Pumarola), Departament de Medicina i Cirurgia Animals, Facultat de Veterinària, Universitat Autònoma de Barcelona, Barcelona, Spain. Corresponding author: Lara Armengou, DVM, Dipl ECEIM, Servei de Medicina Interna Equina, Departament de Medicina i Cirurgia Animals, Facultat de Veterinària, Universitat Autònoma de Barcelona, 08193 Bellaterra, Barcelona, Spain; e-mail: lara.arme ngou@uab.cat. Submitted September 25, 2009; Revised October 27, 2009; Accepted November 19, 2009. Copyright r 2010 by the American College of Veterinary Internal Medicine 10.1111/j.1939-1676.2010.0478.x Abbreviations:

Evaluation of an oral direct factor Xa inhibitor anticoagulant in healthy adult horses

Objective To assess whether an oral direct factor Xa inhibitor (DiXaI) anticoagulant drug used at the low end of the recommended dose in people achieves presumed prophylactic plasma concentrations and does not induce bleeding in horses. Design Experimental study. Setting Field study. Animals Ten healthy adult horses. Interventions A DiXaI was administered at a dose of 0.125 mg/kg every 24 h orally for 4 days. Following a wash-out period of 2 weeks, 8 of 10 horses received daily subcutaneous doses of a low molecular weight heparin (dalteparin) for 4 consecutive days at 50 IU/kg. In both trials, antifactor Xa activity was measured at baseline time and 3 hours after each dose administration. Activated partial thromboplastin time, prothrombin time, hematocrit, erythrocyte agglutination, and platelet aggregation were monitored throughout the study. In addition, an in vitro spiking experiment was performed to demonstrate anticoagulant activity of this DiXaI in horse plasma. Main Results When treated with the DiXaI, this group of horses did not achieve the suggested thromboprophylactic plasma range of antifactor Xa activity (0.1–0.2 IU/mL), except for 1 horse after the first administration of the drug. In contrast, median values of plasma antifactor Xa activity 3 hours after receiving dalteparin were within the prophylactic range (0.16 IU/mL). No hemorrhagic events or erythrocyte agglutination were observed. In vitro addition of this DiXaI caused a concentration-dependent effect in antifactor Xa activity. Conclusions At the low end of the recommended dose in people this oral formulation of DiXaI did not reach prophylactic plasma antifactor Xa activity in this group of healthy adult horses. Further studies are warranted in order to establish the prophylactic dose for horses.OBJECTIVE To assess whether an oral direct factor Xa inhibitor (DiXaI) anticoagulant drug used at the low end of the recommended dose in people achieves presumed prophylactic plasma concentrations and does not induce bleeding in horses. DESIGN Experimental study. SETTING Field study. ANIMALS Ten healthy adult horses. INTERVENTIONS A DiXaI was administered at a dose of 0.125 mg/kg every 24 h orally for 4 days. Following a wash-out period of 2 weeks, 8 of 10 horses received daily subcutaneous doses of a low molecular weight heparin (dalteparin) for 4 consecutive days at 50 IU/kg. In both trials, antifactor Xa activity was measured at baseline time and 3 hours after each dose administration. Activated partial thromboplastin time, prothrombin time, hematocrit, erythrocyte agglutination, and platelet aggregation were monitored throughout the study. In addition, an in vitro spiking experiment was performed to demonstrate anticoagulant activity of this DiXaI in horse plasma. MAIN RESULTS When treated with the DiXaI, this group of horses did not achieve the suggested thromboprophylactic plasma range of antifactor Xa activity (0.1-0.2 IU/mL), except for 1 horse after the first administration of the drug. In contrast, median values of plasma antifactor Xa activity 3 hours after receiving dalteparin were within the prophylactic range (0.16 IU/mL). No hemorrhagic events or erythrocyte agglutination were observed. In vitro addition of this DiXaI caused a concentration-dependent effect in antifactor Xa activity. CONCLUSIONS At the low end of the recommended dose in people this oral formulation of DiXaI did not reach prophylactic plasma antifactor Xa activity in this group of healthy adult horses. Further studies are warranted in order to establish the prophylactic dose for horses.