Serum concentrations of tumor necrosis factor-alpha in neonatal calves with presumed septicemia

This study was performed to determine the concentrations of tumor necrosis factor (TNF) in the serum of neonatal calves with presumed sepsis and determine the correlation between serum concentrations of TNF and the severity and outcome of disease. Thirty-five sick calves < 30 days old that suffered from enteritis, respiratory disease, or both were considered suitable for inclusion in this study by satisfying clinical and laboratory criteria suggestive of septicemia. At admission, blood samples were collected from all calves to determine the prevalence of high concentrations of TNF. The clinical course and outcome of disease then were recorded. Of the 35 calves with presumed sepsis, 10 had high serum TNF concentrations. Scleral injection, weak or absent suckling reflex, sternal or lateral recumbency, unresponsive or comatose state, and death rate of calves with high serum TNF concentration were greater than those values for calves without high serum TNF concentration. Calves with high serum TNF concentration had significantly lower mean IgG (P < .001), globulin (P < .0001), and calcium (P < .0001) concentrations; greater serum creatinine concentrations (P < .0001); and > or = 2+ toxic changes in neutrophils than did calves without high serum TNF concentrations. Mean values for packed cell volume, band neutrophil count, and venous Pco2 were significantly (P < .007) higher in the group of calves with high serum TNF concentration. Results of this study indicate that serum TNF concentration is correlated with clinical criteria of sepsis in neonatal calves. A close association was apparent between disease severity and serum TNF concentrations in this group of calves with presumed septicemia.     

Concentrations of amino acids in the plasma of neonatal foals with septicemia

Concentrations of amino acids in the plasma of 13 neonatal foals with septicemia were compared with the concentrations of amino acids in the plasma of 13 age-matched neonatal foals without septicemia. Analysis of the results revealed significantly lower concentrations of arginine, citrulline, isoleucine, proline, threonine, and valine in the plasma of foals with septicemia. The ratio of the plasma concentrations of the branched chain amino acids (isoleucine, leucine, and valine) to the aromatic amino acids (phenylalanine and tyrosine), was also significantly lower in the foals with septicemia. In addition, the concentrations of alanine, glycine, and phenylalanine were significantly higher in the plasma of foals with septicemia. Therefore, neonatal foals with septicemia had significant differences in the concentrations of several amino acids in their plasma, compared with concentrations from healthy foals. These differences were compatible with protein calorie inadequacy and may be related to an alteration in the intake, production, use, or clearance of amino acids from the plasma pool in sepsis.     

Increase of serum gamma-glutamyltransferase in neonatal Standardbred foals

Serial blood samples were obtained from 16 Standardbred foals from time of birth to postpartum day 28. Sera were obtained and analyzed for gamma-glutamyltransferase (GGT), aspartate transaminase, and immunoglobulin (Ig) G. Presuckle colostrum from the respective mares of these foals was analyzed for GGT activity. Mean serum aspartate transaminase activities were significantly increased above presuckle values by postpartum hour 48 (P less than 0.01) and increased gradually over the first 14 days. Mean serum IgG concentrations were significantly greater than presuckle values by 5 hours after foals first suckled (P less than 0.01) and remained significantly increased during the 28-day sampling period. Serum GGT activity did not differ significantly over the period sampled. The SD were large, since there was a large degree of interindividual variation. Serum GGT activity in the foals was significantly increased over that in the mares throughout the period of the study. The profile of serum GGT activity over time in each foal did not show a pattern of change. There was no postsuckle increase in serum GGT activity nor a correlation between serum GGT activities and IgG concentrations at 24 hours after foals first suckled. Evidence was not obtained to support a colostric source of GGT involved in the increase of serum GGT activity in foals. Serum GGT activity seems to be increased in foals due to endogenous sources.     

Pharmacokinetics of amikacin in critically ill neonatal foals treated for presumed or confirmed sepsis

Fourteen foals less than four days of age were treated with the aminoglycoside, amikacin sulphate, and either penicillin or ampicillin for septicaemia, pneumonia, and/or failure of passive immunoglobulin transfer. Serum amikacin concentrations were determined at three times during an 8 or 12 h dosing interval. A 7.0 mg/kg bodyweight dose of amikacin every 8 h was appropriate. Prematurity did not influence mortality. All seven premature foals survived, whereas four of the seven full term foals died. Uraemia in three foals was caused by urinary bladder rupture; amikacin-induced nephrotoxicity was not recognised by clinical chemistries (elevations in serum creatinine or blood urea nitrogen concentrations) or post-mortem findings.     

Pharmacokinetics and serum concentrations of cephapirin in neonatal foals

Six healthy foals, from 4 to 6 days of age, were given a single IM injection of sodium cephapirin (250 mg/ml) at a rate of 20 mg/kg of body weight. Serum concentrations of cephapirin were measured serially over an 8-hour period. The mean peak serum concentration was 21.2 micrograms/ml at 10 minutes. The overall elimination rate constant was 1.06/hr and the elimination half-life was 0.70 hour. The apparent volume of distribution at steady state was 1.06 L/kg and plasma clearance was 1,105 ml/hr/kg.     

Immunologic disorders in neonatal foals.

Foals live in an environment heavily populated by bacteria, many of which are capable of causing disease. Development of infection,however, is the exception rather than the rule. The ability of the foal to prevent infection by most pathogens is the result of a sophisticated set of defense mechanisms. These defense mechanisms can be divided into adaptive and innate immunity. Innate immunity encompasses defense mechanisms that pre-exist or are rapidly induced within hours of exposure to a pathogen. Conversely, adaptive or acquired immunity represents host defenses mediated by T and B lymphocytes, each expressing a highly specific antigen receptor and exhibiting memory during a second encounter with a given antigen. Immunologic disorders are relatively common in foals compared with their occurrence in adult horses. This article summarizes the current understanding of the equine fetal and neonatal immune system and reviews common immunodeficiency disorders as well as disorders resulting from allogenic incompatibilities.     

Orthopedic disorders in neonatal foals.

The first month of life is a vulnerable time for foals. They must adjust to their environment while they are still compromised immunologically, and their musculoskeletal system is rapidly growing and adjusting to stresses from an increasing amount of exercise. Therefore, if a foal is born with or acquires an abnormality or disease related to the musculoskeletal system, rapid adjustments must be made to allow the foal to grow and respond so that future athletic performance will not be compromised. Problems must be identified early, which requires thorough examinations. This article summarizes treatment options for orthopedic disorders that present or become clinically evident within the first month of life.     

Abdominal surgery in neonatal foals.

Abdominal surgery in foals under 30 days old has become more common with improved neonatal care. Early recognition of a foal at risk and better nursing care have increased the survival rates of foals that require neonatal care. The success of improved neonatal care also has increased the need for accurate diagnosis and treatment of gastrointestinal, umbilical, and bladder disorders in these foals. This chapter focuses on the early and accurate diagnosis of specific disorders that require abdominal exploratory surgery and the specific treatment considerations and prognosis for these disorders.     

Tumor necrosis factor activity in the circulation of horses given endotoxin

Serum and plasma from horses injected with endotoxin was examined for cytotoxic activity. Each of the cell lines, L929 and WEHI 164 clone 13, was sensitive to the cytotoxic effects of equine serum; however, a precipitation artifact caused by the use of isopropanol in the WEHI assay limited the use of this assay to samples containing less than 2 mg of protein/ml. In foals treated with a sublethal IV bolus of 5 micrograms of lipopolysaccharide (LPS)/kg and in adult horses given a low-dose continuous infusion of LPS (30 ng/kg/h for 4 hours), cytotoxic activity was detected in all serum or plasma samples taken between 30 minutes and 4 hours after LPS infusion began. In horses given either continuous or bolus LPS infusions, circulating cytotoxic activity peaked at 1 to 2 hours before decreasing sharply. The onset of pyrexia after LPS infusion coincided with the appearance of circulating cytotoxic activity, but the temperature remained high, even after cytotoxic activity disappeared. Treatment of horses with flunixin meglumine (1 mg/kg) appeared to blunt the pyrexic effect of low-dose continuous LPS infusion, but had no significant effect on circulating cytotoxic activity. Incubation of serum samples with an antibody raised against a portion of human tumor necrosis factor (TNF) resulted in the removal of greater than 90% of serum cytotoxicity, suggesting strongly that the cytotoxic activity was attributable to TNF. These findings are consistent with the hypothesis that TNF is an early acting mediator of the effects of endotoxin in the horse.     

Listeric septicemia with meningitis in a neonatal calf.

A 9-days-old calf which had exhibited depression and difficulty to stand and walk was examined pathologically and bacteriologically. The primary pathological changes consisted of multifocal necrosis in several visceral organs and fibrinopurulent meningitis. The necrotic lesions were most frequently found in the liver, and accompanied with mononuclear cell infiltration and Gram-positive small bacilli. The organisms were also present in the foci of mononuclear cells at the central gray matter of the mesencephalon. Listeria monocytogenes was isolated from the brain and other organs of the whole body.     

Antimicrobial-induced endotoxin and cytokine activity in an in vitro model of septicemia in foals

OBJECTIVE: To determine which antimicrobials that are used to treat neonatal foals with septicemia attributable to Escherichia coli will minimize endotoxin release from bacteria and subsequent activity of inflammatory mediators while maintaining bactericidal efficacy. SAMPLE POPULATION: Blood samples from 10 healthy foals. PROCEDURE: Escherichia coli isolates A and B were isolated from 2 septicemic foals, and minimal inhibitory concentrations (MIC) were determined for 9 antimicrobials. Five of these antimicrobials were tested in vitro at 2 and 20 times their respective MIC. Whole blood or mononuclear cells grown in tissue-culture media were incubated with 105 colony-forming units of E. coli and each antimicrobial or saline (0.9% NaCl) solution. After 6 hours, number of viable bacteria remaining was determined, and supernatant was tested for endotoxin and tumor necrosis activity. RESULTS: Testing in whole blood was compromised by bactericidal effects of the blood itself. In mononuclear cell suspensions, each antimicrobial significantly reduced the number of viable bacteria to low or undetectable amounts. Antimicrobials did not differ significantly in efficacy of bacterial killing. Amikacin used alone or in combination with ampicillin resulted in significantly less endotoxin activity than did ampicillin, imipenem, or ceftiofur alone. There was a correlation between TNF-alpha and endotoxin activity. CONCLUSIONS AND CLINICAL RELEVANCE: Aminoglycosides appear less likely to induce endotoxemia and TNF-alpha synthesis during bactericidal treatment of E. coli septicemia, compared with beta-lactam antimicrobials. Use of ampicillin, imipenem, or ceftiofur in the treatment of septicemic neonatal foals should be accompanied by appropriate treatment for endotoxemia.     

Nutritional support for neonatal foals.

In recent years, equine neonatal medicine has made significant advances. The importance of nutritional support for the sick neonatal foal has been recognized, and methods of providing that sup-port have been developed. Today, the clinician has many options when designing a nutritional plan for the neonatal foal. When the foal's gut permits, enteral diets are an inexpensive source of nutrients. Under conditions where the gut requires rest, methods for delivering nutrients by the parenteral route have also been developed. In this article, the nutrition of the normal and sick foal is described. Guidelines for designing a nutritional plan are also reviewed.     

Ocular conditions of neonatal foals.

A discussion of ocular conditions of foals with an emphasis on congenital and inherited disorders is presented. An understanding of the normal postnatal development of the eye and adnexae is important. Recognition of inherited abnormalities is essential when giving advice on breeding suitability, and prompt attention or referral of deteriorating ocular conditions in foals ensures the best outcome for future use. Congenital conditions may be recognized for the first time in older animals during their first thorough eye examination.     

Fibrin deposits and organ failure in newborn foals with severe septicemia

Background: Septicemia in human neonates frequently is complicated by activation of the coagulation system, disseminated intravascular coagulation (DIC) and multiple organ failure syndrome, which may contribute to high mortality. In adult horses with DIC, the lung has been the organ most frequently affected by fibrin deposits. In addition, in vivo studies suggest that hemostatic mechanisms may be immature in foals <1‐day old. Hypothesis: Newborn foals with severe septicemia have fibrin deposits in their tissues independently of their age, and these fibrin deposits are associated with organ failure. Animals: Thirty‐two septic and 4 nonseptic newborn foals euthanized for poor prognosis. Methods: Tissue samples (kidney, lung, and liver) collected on postmortem examination were stained with phosphotungstic acid hematoxylin (PTAH) and immunohistochemistry (IHC) for blind histologic examination. A fibrin score (grades 0–4) was established for each tissue sample and for each foal. Medical records were reviewed for assessing clinical evidence of organ failure during hospitalization. Results: Fibrin deposits were found in most septic foals (28/32 when using IHC and 21/32 when using PTAH), independently of the age of the foal. The lung was the most affected tissue (97% of the septic foals). Additionally, organ failure was diagnosed in 18/32 septic foals (8 with respiratory failure, 14 with renal failure), although a statistical association with severe fibrin deposition was not identified. Conclusions and Clinical Importance: Nonsurviving septic foals have fibrin deposits in their tissues, a finding consistent with capillary microthrombosis and DIC.     

Iron toxicity in neonatal foals

Newborn Shetland foals died of acute hepatic failure following oral administration of approximately 16 mg/kg body weight ferrous fumarate. Lesions in these foals were indistinguishable from lesions in foals given an oral digestive inoculant containing ferrous fumarate and were also similar to the syndrome characterised as 'toxic hepatopathy' in foals in the United States in 1983. We conclude that foals are susceptible to toxicity from low doses of iron compounds in the first few days of life. Vitamin E and selenium deficiency may contribute to this susceptibility.     

Musculoskeletal disorders in neonatal foals

Angular limb deformities are not uncommon in foals. Mild angular deviation due to laxity of supporting soft tissues often resolves spontaneously. However, external splinting or casting may be needed in severe cases or in those that do not resolve. When incomplete ossification of carpal or tarsal bones is the cause of the limb deformity, external support is mandatory to prevent further deformation and abnormal development of the bones. When epiphyseal and metaphyseal abnormalities cause axial deviation, surgical intervention is usually necessary. Circumferential periosteal transection and/or transphyseal bridging are methods used. The choice is dictated by the type and severity of the deformity. Flexor contractures of the forelimb vary greatly in degree and joints affected. Physical therapy combined with intermittent splint application is often successful, but surgical intervention may be necessary in unresponsive cases. Flexor tendon laxity is usually self-correcting but physical therapy, restricted exercise, and splinting may be needed. Rotational abnormalities are easier to correct in the forelimbs than in the hind limbs. Correction is usually accomplished by frequent corrective hoof trimming. Miscellaneous anomalies of the musculoskeletal system may sometimes be amenable to surgical correction, although the potential disadvantages must be carefully considered. Septic arthritis is a frequent sequela to neonatal septicemia and must be treated aggressively and early in its development. Appropriate systemic antibiotics, joint lavage, and rest are indicated. Neonatal osteomyelitis has a poor prognosis and requires prompt, vigorous therapy; even then, growth anomalies of the limb or contiguous septic arthritis may develop and further worsen the prognosis. Early accurate diagnosis and prompt appropriate therapy are vital in treating musculoskeletal disorders in foals, especially when a successful outcome is judged by the animal becoming a functional athlete.     

Antimicrobial therapy in neonatal foals

There are several differences in treatment of neonatal foals with antimicrobials, compared to mature horses. Firstly, the dose of many antimicrobials is different in the foal. For orally administered drugs, this may also affect their efficacy, due to different enteral absorption. Secondly, neonatal foals are not yet hindgut fermentors and this allows antimicrobials with a high propensity to cause colitis in mature horses to be used. Thirdly, toxicities are different and some antimicrobials used in mature horses, such as enrofloxacin, are not suitable for use in foals. Foal-specific information is therefore needed for their safe and effective treatment with antimicrobials.