Tumor necrosis factor and interleukin-6 activity and endotoxin concentration in peritoneal fluid and blood of horses with acute abdominal disease.

The purpose of this study was to evaluate the diagnostic and prognostic significance of tumor necrosis factor-alpha (TNF) and interleukin-6 (IL-6) activities and endotoxin concentration in blood and peritoneal fluid of 155 adult horses with acute abdominal disease (colic). Samples also were obtained from 20 healthy adult horses. Blood and peritoneal fluid supernatant TNF and IL-6 activities and endotoxin concentration were significantly greater in horses with colic, compared with healthy horses. In horses with colic, the peritoneal fluid endotoxin concentration and TNF and IL-6 activities were significantly greater than those in blood. Within the colic group, peritoneal fluid IL-6 activity was the analyte that was most frequently increased. Blood and peritoneal fluid supernatant TNF and IL-6 activities were significantly greater when endotoxin was detected in the same sample. Blood and peritoneal fluid IL-6 activity was significantly greater in horses with inflammatory or strangulating lesions, compared with horses having nonstrangulating or noninflammatory lesions. Compared with all other data categories, diagnostic accuracy for nonsurvival was greatest (80%) when blood IL-6 activity exceeded 60 units/mL. The results of this study indicate that endotoxin was present in the peritoneal cavity of at least one third of horses with any acute disease of the abdomen. In horses presented for colic, blood or peritoneal fluid IL-6 activity was more useful than either TNF activity or endotoxin concentration for distinguishing lesion type. Although diagnostic accuracy for the prediction of nonsurvival was good for all of the analytes, negative values were more useful in the prediction of a favorable outcome than were abnormally increased values in the prediction of mortality.

Removal of an ectopic left kidney through a ventral midline celiotomy in a calf.

A 4-month-old Holstein heifer was examined because of poor growth, weight loss, dysuria, hematuria, pyuria, and a palpable mass in the right caudal quadrant of the abdomen. Clinicopathologic abnormalities included hyperfibrinogenemia, hyperproteinemia, anemia, and leukocytosis, and were consistent with chronic inflammation. Results of ultrasonographic evaluation of the umbilical cord remnants were suggestive of urachal abscess formation. Transabdominal ultrasonography of the kidneys was attempted; the right kidney appeared normal, but the left kidney could not be imaged. The calf was anesthetized and a ventral midline celiotomy was performed. The left kidney was larger than normal, was multilobulated, and contained multiple abscess. It had also broken through the peritoneum and was located in the peritoneal cavity. Unilateral nephrectomy and resection of umbilical cord remnants were performed. The calf recovered without complications and was healthy 5 years later. In this calf, ventral midline celiotomy provided sufficient surgical exposure for removal of the ectopic left kidney and resection of umbilical cord remnants.

Equine degenerative myeloencephalopathy.

EDM is a neurologic disease of young horses characterized by the insidious development of symmetric ataxia. Decreased or absent cutaneous trunci reflex or slap test responses are considered clinical signs that increase the index of suspicion for this disease. In addition, concurrent predisposing factors, such as familial history, inadequate access to green pasture, and possible exposure to wood preservatives or insecticides, provide further supporting evidence for a clinical diagnosis. Vitamin E deficiency and a hereditary predisposition currently are considered the most significant factors in the pathogenesis of this disease. Histopathologically the lesions of EDM are those of neuraxonal dystrophy, characterized by prominent axonal and dendritic swelling, mild glial proliferation, and neuronal depletion and atrophy with lipofuscin-like pigment accumulation. Animals predisposed to EDM or with a clinical diagnosis of EDM should receive oral alpha-tocopherol acetate supplementation. Improvement in clinical signs may be seen following long-term treatment, but in general, the prognosis for complete recovery is poor.

Endotoxin induced expression of tumour necrosis factor, tissue factor and plasminogen activator inhibitor activity by peritoneal macrophages.

Peritoneal fluid was collected aseptically from 30 healthy adult horses and 115 horses with acute gastrointestinal disease and supernatant was separated from cells by centrifugation followed by freezing until assayed for endotoxin and tumour necrosis factor activity. Peritoneal macrophages obtained from healthy horses were incubated in vitro for 3, 6, 12 or 24 h in the absence (media control) or presence of Escherichia coli 055:B5 endotoxin (final concentrations of 1, 10, 100 or 1000 ng/ml). Macrophages obtained from horses with acute gastrointestinal disease were incubated for 12 h in the absence (media control) or presence of 100 ng endotoxin/ml. At the conclusion of the incubation, macrophage supernatants were collected and frozen at -70 degrees C until analysed for tumour necrosis factor activity. Macrophage membranes were lysed and frozen at -70 degrees C until assayed for tissue factor and plasminogen activator inhibitor type 2 activity. Compared to cells incubated with media, incubation of macrophages, obtained from healthy horses, with endotoxin significantly increased tumour necrosis factor, tissue factor and plasminogen activator inhibitor type 2 activity. These increases were dependent on the endotoxin concentration and the duration of incubation. Compared to cells incubated with media alone, incubation of macrophages, obtained from horses with acute gastrointestinal disease with endotoxin, significantly increased tumour necrosis factor and tissue factor activity. Endotoxin induced tumour necrosis factor activity in vitro was significantly less for macrophages from horses with acute gastrointestinal disease, as compared to that produced by similarly treated cells obtained from healthy horses. For those horses with acute gastrointestinal disease, macrophages obtained from horses with either endotoxin or tumour necrosis factor activity in the peritoneal fluid supernatant had significantly less endotoxin induced tumour necrosis factor in vitro, as compared to similarly treated cells obtained from horses without endotoxin or tumour necrosis factor activity in the peritoneal fluid supernatant. The results of this study indicate that exposure of equine peritoneal macrophages to endotoxin results in a significant increase in tumour necrosis factor, tissue factor and plasminogen activator inhibitor type 2 activity. After in vitro exposure to endotoxin, there is significant down-regulation of inflammatory mediator production by peritoneal macrophages obtained from endotoxaemic horses. These results suggest that these macrophages may exhibit early endotoxin tolerance.

Intravascular and peritoneal coagulation and fibrinolysis in horses with acute gastrointestinal tract diseases.

Components of the coagulation and fibrinolytic cascades, prothrombin and activated partial thromboplastin times, endotoxin activity, and albumin concentration were measured in blood and peritoneal fluid from 20 healthy horses and from 153 horses with acute gastrointestinal tract diseases at admission. Overall, 77% (117/153) of affected horses survived to discharge from the hospital, and 85% (82/97) of horses discharged were reported to be normal 9 to 14 months later. Significant differences in hemostatic factors were more common in peritoneal fluid than in blood. Tissue plasminogen activator, plasminogen, protein C, antithrombin III, and alpha 2-antiplasmin activities and concentrations of fibrinogen and fibrin degradation products were significantly (P < 0.05) greater in peritoneal fluid from horses with colic, and, with the exception of fibrinogen concentration, were associated with detection of endotoxin. Higher values for these variables, except tissue plasminogen activator activity, were significantly (P < 0.05) associated with survival. Plasminogen, antithrombin III, and alpha 2-antiplasmin activities were significantly (P < 0.05) greater in peritoneal fluid from horses with inflammatory or strangulating lesions, compared with those in horses with simple colic. Plasminogen-activator inhibitor type 1 activity, fibrin degradation products concentration, and prothrombin time were significantly (P < 0.05) greater in the blood of horses with colic. Survival was inversely associated with significantly (P < 0.05) greater intravascular concentrations of fibrin degradation products and fibrinogen and prothrombin time. This study revealed marked contrasts between peritoneal and intravascular coagulation and fibrinolysis in horses with colic, indicating that inferences regarding the peritoneal environment, particularly with respect to fibrinolytic capacity, should not be made on the basis of factors measured in blood.

Hemostatic indices in healthy foals from birth to one month of age.

Hemostatic indices were determined in 45 healthy light breed foals, from birth to 1 month of age, and in 20 healthy adult (> 2 years of age) light breed horses. Blood samples were obtained from each foal at 4 ages: 1) < 24 hours, 2) 4-7 days, 3) 10-14 days, and 4) 25-30 days. The following hemostatic indices were determined: platelet count; prothrombin and activated partial thromboplastin times; activity concentrations of protein C, antithrombin III, plasminogen, alpha-2 antiplasmin, tissue plasminogen activator, and plasminogen activator inhibitor-1; plasma protein C antigen and fibrinogen concentrations; and serum fibrin degradation products concentration. Prothrombin and activated partial thromboplastin times were significantly longer at birth than in older foals. The plasma concentrations of the following were significantly lower at birth than in older foals: antithrombin III, plasminogen and tissue plasminogen activator activities, protein C antigen, and fibrinogen. Concentrations of the following were significantly higher at birth than in older foals: protein C and plasminogen activator inhibitor-1 activities and fibrin degradation products. These results indicate that hemostatic indices of neonatal foals differ significantly from those of older foals and adults. With the exceptions of antithrombin III and tissue plasminogen activator activities, all hemostatic indices measured in foals at 1 month of age were equivalent to adult values.

Fibrinolytic activity in plasma from horses with gastrointestinal diseases: changes associated with diagnosis, surgery, and outcome.

Plasma fibrinolytic activity was evaluated over 5 consecutive days in 59 horses admitted to the Large Animal Teaching Hospital with acute gastrointestinal diseases. Only horses hospitalized for at least 5 days were included in the study. Tissue plasminogen activator (tPA) and plasminogen activator inhibitor type-1 (PAI-1) were quantitated using standard chromogenic activity assays. Statistical analyses were performed using analysis of variance; differences were considered significant when P < or = .05. Activity of PAI-1, the primary endogenous inhibitor of fibrinolysis, was significantly increased on hospital days 2, 4, and 5 in horses that died, when compared with those that were discharged from the hospital. Plasma PAI-1 activity was not different at admission, but was significantly increased on hospital days 2 and 3 in horses that underwent surgery, when compared with those that did not, suggesting an acute phase response to surgical intervention. Horses with strangulating intestinal lesions had significantly increased PAI-1 activity on day 3, while PAI-1 activity was significantly greater in horses with inflammatory conditions at the time of admission, when compared with horses with strangulating or nonstrangulating/noninflammatory lesions. Among all horses, PAI-1 activity was significantly higher and tPA activity was significantly lower on day 2 when compared with other hospital days. These results suggest that fibrinolysis is inhibited early in the course of inflammatory gastrointestinal diseases and in response to surgery. In addition, among all horses, the prognosis for survival was poor for those with persistently increased PAI-1 activity, reflecting treatment failure and the loss of hemostatic regulation.

Regulation of equine fibrinolysis in blood and peritoneal fluid based on a study of colic cases and induced endotoxaemia.

Much of the pathophysiology associated with equine gastrointestinal diseases is attributed to the effects of endotoxin on haemostasis. Because little is known about the responses of the equine fibrinolytic system to endotoxin, regulation of the system was investigated. Tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor type-1 (PAI-1) were identified as the primary plasminogen activator and plasminogen activator inhibitor, respectively, in equine blood. Under experimental conditions, the equine fibrinolytic system responded to endotoxin in a manner similar to that reported in man, with an early, transient increase in t-PA activity followed by an overwhelming and prolonged increase in activity of PAI-1. To investigate the response of the equine fibrinolytic system to clinical endotoxaemia, endotoxin concentrations were measured in plasma and peritoneal fluid, and activities of t-PA and PAI-1 were compared between healthy horses (n = 38) and horses with naturally occurring gastrointestinal diseases (n = 150). It was observed that plasma PAI-1 and peritoneal t-PA were increased concurrently in abnormal horses; and that these increases were associated with the presence of endotoxin. The results of this study suggest that 1) fibrinolysis is regulated in horses in a manner similar to that in man; 2) regulation of fibrinolysis is altered in endotoxaemic horses with gastrointestinal diseases; 3) events occurring in the vascular system may not reflect those in the peritoneal cavity; and 4) t-PA activity is increased in the peritoneal fluid of endotoxaemic horses with gastrointestinal diseases.

Surgical treatment of sacral fracture in a horse.

An 8-year-old Arabian stallion had signs of severe tailhead pruritus and slowly progressive loss of tail tone for 3 months. Palpation per rectum and radiography of the sacrocaudal region revealed a transverse, ventrally displaced fracture of the caudal portion of the sacrum. Surgical decompression and tail amputation resulted in complete recovery of athletic and reproductive function. Evidence of cauda equina neuritis was not seen on histologic examination of nerve roots obtained at surgery.

Testicular seminoma associated with torsion of the spermatic cord in two cryptorchid stallions.

Two adult horses had colic attributable to spermatic cord torsion and strangulation of abdominally retained neoplastic testes. Both horses had caudal abdominal soft tissue masses palpable per rectum. One horse was treated successfully by surgical removal of the testis, and the other was euthanatized without treatment. Histopathologic diagnosis of the involved testes was testicular seminoma. Spermatic cord torsion of an abdominally retained testis should be considered in the differential diagnosis of signs of abdominal pain in cryptorchid stallions, especially those with a palpable caudal abdominal mass.

Septicemia, atrial fibrillation, cardiomegaly, left atrial mass, and Rhodococcus equi septic osteoarthritis in a foal.

A foal with vegetative bacterial endocarditis affecting the wall of the left atrium was treated successfully with cefotaxime, erythromycin, and rifampin. Bacterial isolates included Escherichia coli from blood and Rhodococcus equi from a P-type osteomyelitic lesion of the left third metatarsal bone and from synovial fluid from the left metatarsophalangeal joint. Cardiac complications included cardiomegaly and atrial fibrillation, which responded to treatment with digoxin and quinidine sulfate. Cardiac function was considered normal 18 months after treatment. Bacteriologic cure of osteoarthritis was achieved by use of surgical debridement, lavage, and local and systemic antimicrobial treatment; however, lameness developed 18 months after treatment when training for flat racing was begun. Radiography revealed chronic degenerative joint disease.

Hypoperfusion of the small intestine during slow infusion of a low dosage of endotoxin in anesthetized horses.

The effects of intravenous infusion of endotoxin for 30 minutes at a cumulative dosage of 0.03 micrograms/kg on average carotid arterial pressure, and on average arterial pressure, capillary pressure, venous pressure, total vascular resistance, precapillary resistance, postcapillary resistance, and capillary filtration coefficient in the jejunum were compared to the effects of intravenous infusion of 0.9% sodium chloride solution in 6 anesthetized horses. Endotoxin significantly reduced intestinal venous blood flow by inducing vasoconstriction. Increased vascular resistance resulted from increased precapillary resistance. The capillary filtration coefficient was unchanged by endotoxin. These results suggest that intestinal vasoconstriction occurs during the compensatory stages of endotoxemia.

Umbilical cord remnant abscess in a yearling colt.

An abscess of the external umbilical remnant and umbilical vein remnant was diagnosed in a 16-month-old colt, using ultrasonography. Because of the colt's size, primary closure of the surgical incision after umbilical cord resection was not complete. Vertical mattress stainless steel sutures and stents were used, and healing was by second intention. Intervening gas-filled viscera made it impossible to visualize ultrasonographically the bladder of umbilical artery remnants in a colt of this age.

Clinical, ultrasonographic, and surgical findings in foals with umbilical remnant infections.

Infection of umbilical arteries, umbilical vein, and/or urachus was diagnosed ultrasonographically in 33 foals 1 to 90 days old (mean, 17.7 +/- 17.3 days). In these foals, the most common initial problems were umbilical abnormalities, septic arthritis, and/or neonatal septicemia. In 16 foals, abnormalities of the external umbilical stalk were noticed on admission. Abnormalities of the internal umbilical structures were identified when enlargement and echogenic material (fluid and/or gas) were imaged ultrasonographically within these structures. Multiple structures were affected in 23 foals, with the urachus the most commonly affected structure. Surgical findings confirmed ultrasonographic identification of infected umbilical structures in 23 foals. Twenty-two samples from affected umbilical remnants submitted for culture at surgery were positive for bacterial growth. Multiple organisms were isolated in 15 cultures. Escherichia coli and beta-hemolytic streptococci were the most common isolates. Two foals died of late complications associated with surgical resection, 1 foal treated surgically and 3 foals treated medically died or were euthanatized because of other complications, and the remaining 27 foals lived.

Ultrasonography of umbilical structures in clinically normal foals.

The umbilical arteries, urachus, and umbilical vein were scanned ultrasonographically in 13 clinically normal foals that ranged in age from 6 hours to 4 weeks. Sonograms were obtained using a 7.5-MHz sector scanner transducer placed across the midline of the ventral portion of the foal's abdominal wall. The umbilical vein was scanned from the umbilical stalk to its entrance into the hepatic parenchyma. The mean (+/- SD) diameter of the umbilical vein was 0.61 +/- 0.20 cm immediately cranial to the umbilical stalk, 0.52 +/- 0.19 cm midway between the umbilicus and liver, and 0.6 +/- 0.19 cm at the liver. The urachus and umbilical arteries were scanned from the umbilical stalk to the apex of the urinary bladder and had a mean total diameter of 1.75 +/- 0.37 cm at the bladder apex. The umbilical arteries also were scanned along either side of the bladder and had a mean diameter of 0.85 +/- 0.21 cm. These measurements and the ultrasonographic appearance of the internal umbilical structures from clinically normal foals can be used as references to diagnose abnormalities of the umbilical structures in neonatal foals.