The response of the horse to formyl-methionyl-leucyl-phenylalanine in vivo.
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Biomedical subjects
Publications and source records attributed to J H Lumsden.
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The effects of acetoacetic acid, acetone, bilirubin, beta-carotene, three cephalospoprin antibiotics, glucose, hemoglobin and lipid on the kinetic Jaffé reaction and an enzymatic reaction for the determination of creatinine concentration were studied in bovine, canine, feline and equine serum. There were no obvious species' differences. The kinetic Jaffé reaction was unaffected by the addition of beta-carotene and hemoglobin. Acetone, cefazolin, cefoxitin, ceftiofur and glucose caused a positive bias while acetoacetic acid, bilirubin, and lipid caused a negative bias when added to the kinetic Jaffé reaction. The enzymatic reaction was unaffected by the addition of acetoacetic acid, acetone, beta-carotene, cefazolin, cefoxitin, glucose and hemoglobin while added lipid, bilirubin and ceftiofur caused a negative bias in the test results. Over all species and interferents, there was no difference in the precision of the two assay methods. In a series of sera from hospitalized patients, the two methods were highly correlated in a linear fashion. The enzymatic creatinine assay deals effectively with most interferents but has a greater cost and shorter shelf-life compared with the kinetic Jaffé reaction.
Phenobarbital was administered orally to seven healthy cats at a dose of 5 mg/kg once a day for 21 days. Serum phenobarbital concentrations were determined using a commercial immunoassay technique. A one-compartment model was used to describe the final elimination curve. The elimination half-life (t1/2 b) after the final day of treatment was 43.3 +/- 2.92 h. The large apparent volume of distribution of 695.0 +/- 43.9 mL/kg suggests that the drug was widely distributed within the body. The t1/2 b following multiple oral administration was significantly shorter than previously reported for a single oral dose of phenobarbital in the cat. Analysis of pharmacokinetic results after days 1 and 21 of treatment suggested that the elimination kinetics of phenobarbital did not change significantly with multiple oral administration. It appears that differences in elimination kinetics can exist between populations of cats. These differences emphasize the need for individual monitoring of cats receiving phenobarbital.
In order to determine which variables are useful and accurate in estimating prognosis in horses with abdominal pain, data were analyzed from 231 horses presented at a veterinary teaching hospital. Using multiple stepwise discriminant analysis in a recursive partition model, we obtained a decision protocol that identified survivors and nonsurvivors. The prevalence of survivors was 61% in this population. The sensitivity, specificity, and positive and negative predictive values of this model were 71, 83, 87 and 65%, respectively. This decision protocol was validated by Jackknife classification and also by evaluation with a referral population of 100 horses in which the prevalence of survivors was 83%. This led to sensitivity, specificity, and positive and negative predictive values of 83, 78, 94 and 50%, respectively.
Phenobarbital was administered to eight healthy cats as a single intravenous dose of 10 mg/kg. Serum phenobarbital concentrations were determined using an immunoassay technique. The intravenous data were fitted to one-, two- and three-compartment models. After statistical comparison of the three models, a two-compartment model was selected. Following intravenous administration, the drug was rapidly distributed (distribution half-life = 0.046 +/- 0.007 h) with a large apparent volume of distribution (931 +/- 44.8 mL/kg). Subsequent elimination of phenobarbital from the body was slow (elimination half-life = 58.8 +/- 4.21 h). Three weeks later, a single oral dose of phenobarbital (10 mg/kg) was administered to the same group of cats. A one-compartment model with an input component was used to describe the results. After oral administration, the initial rapid absorption phase (absorption half-life = 0.382 +/- 0.099 h) was followed by a plateau in the serum concentration (13.5 +/- 0.148 micrograms/mL) for approximately 10 h. The half-life of the terminal elimination phase (76.1 +/- 6.96 h) was not significantly different from the half-life determined for the intravenous route. Bioavailability of the oral drug was high (F = 1.20 +/- 0.120). Based on the pharmacokinetic parameters determined in this study, phenobarbital appears to be a suitable drug for use as an anticonvulsant in the cat.
We tested the hypothesis that lymphocytes from swine with susceptibility to malignant hyperthermia (MH) had calcium extrusion activity higher than unaffected swine. Cytoplasmic concentration of ionized calicum was determined by use of dual emission spectrofluorometry and measurement of the ratio of free to calcium-bound form of the fluorescent calcium dye indo-1. Net calcium accumulation and unidirectional calcium extrusion rate were dependent on intracellular calcium concentration. Calcium extrusion from calcium-loaded lymphocytes was monitored while calcium influx was inhibited by suspending the cells in calcium-free medium with a calcium chelator. Net calcium accumulation of untreated lymphocytes was monitored in calcium-replete medium. A novel method of calculation of ionized calcium was used. This method confirmed our previous findings of lower ionized calcium concentration (86 +/- 40 and 370 +/- 216 nmol/L; P less than 0.01) and slower rates of calcium accumulation 39 +/- 16 and 127 +/- 52 nmol/L/min) in untreated lymphocytes from MH-susceptible swine compared with controls. These changes were attributable to calcium extrusion activity two- to three-fold higher in lymphocytes of MH-susceptible swine (154 +/- 36 and 408 +/- 47 nmol/L/min at 175 nmol/L; 972 +/- 111 and 1,690 +/- 505 nmol/L/min at 425 nmol/L). These data were compatible with our model of higher calcium extrusion activity being a compensatory adaptation of MH-susceptible swine lymphocytes to their hypersensitivity to stimuli that increase cytoplasmic calcium concentration.
From May 1, 1983 to April 1, 1985, 142 operations were performed on horses with signs of acute abdominal pain (colic), using a ventral midline incision. Seventy-eight horses lived for at least 15 days after surgery or had acute dehiscence and were included in the study. Seventy horses had surgery once, and 8 horses had surgery 2 or more times. Six-month follow-up evaluation was obtained for 66 horses that had 1 surgery and for 6 horses that had multiple surgeries. Incisional complications included drainage (including infection), acute dehiscence, hernia, and suture sinus formation. The effects of preoperative peritoneal fluid presence, enterotomy or resection, suture material and pattern used in the linea alba, type of skin closure and use of a sutured-on stent bandage on the incidence of incisional complications were investigated. The complication of incisional infection rate associated with a near-far-far-near suture pattern vs simple interrupted pattern in the linea alba was the only statistically significant (P less than 0.05) difference observed.
The clinician never has had a better selection of user friendly analytical systems for in-clinic use. Selection of a system should be made only after several questions have been answered, including: What is the technical knowledge and experience of the persons who will use the system? Who will initiate and supervise a quality assurance program? Which analysis and what volume of samples are anticipated now and in the future? The estimated cost per test should include the total cost of instrumentation and maintenance, calibrators, controls, reagents, and technical and supervisory time. Have the methods been validated for the animal species involved and are adequate reference values available? Read the package inserts completely for each analyte. Do not rely on the advice of salespeople for guidance in answering many of these questions, but do question them carefully about statements made, especially regarding warranties and technical service. For those clinicians willing to accept the responsibilities associated with in-clinic testing, an increased awareness of laboratory medicine and a resulting increased interest and ability to provide quality medical care can be expected.
In many instances, the cause for malassimilation can be determined with ease, but finding the cause sometimes can be elusive and require the use of sophisticated laboratory techniques not available to the general veterinary practitioner. In either case, the clinician, whether generalist or specialist, must make an informed decision based on the results of many different testing modalities, and not only on the results of the laboratory tests described here. A flow chart is provided to assist the diagnostician in selecting and applying the more clinically oriented laboratory tests useful in dealing with a patient with chronic diarrhea and weight loss.
In order to determine which variables are useful in identifying horses with abdominal pain requiring surgery, data were analysed from 219 horses presented at one veterinary teaching hospital. Using multiple stepwise discriminant analysis with a recursive partitioning algorithm, we obtained a decision tree that identifies surgical and non-surgical patients. The prevalence of surgical patients was 79 per cent in this population. The sensitivity, specificity, and positive and negative predictive values of this decision tree were 99 per cent, 55 per cent, 90 per cent and 99 per cent respectively. Compared to the clinical decision, this decision tree yielded more false positives (11 per cent) but almost eliminated false negatives (1 per cent). This decision tree was validated by the jack-knife method and also by evaluation using a new sample in a second veterinary teaching hospital in which the prevalence of surgical patients was 55 per cent. This led to sensitivity, specificity and positive and negative predictive values of 93 per cent, 73 per cent, 81 per cent and 89 per cent respectively.
We tested the hypothesis that lymphocytes from swine with susceptibility to malignant hyperthermia (MH) had increased sensitivity to the membrane-perturbing effects of halothane that increase cytoplasmic calcium. Cytoplasmic concentration of ionized calcium in lymphocytes isolated from blood was determined in the presence and absence of halothane for 10 Pietrain x Poland China swine that were susceptible to MH and 20 Yorkshire swine that were resistant to MH. Calcium was determined by dual-emission spectrofluorometry and by measuring the ratio of free to calcium-bound form of the fluorescent calcium dye Indo-1. Mean values for calcium concentrations in lymphocytes from MH-susceptible (MHS) swine were 80% less than control values (40.5 +/- 38.8 and 185.3 +/- 91.6 nmol/L; P less than 0.01). Untreated lymphocytes from MHS swine accumulated calcium at half the rate observed for controls. Exposure to 1 mmol/L halothane resulted in a 3-fold increase of free calcium concentration to 127.9 +/- 81.3 nmol/L in the lymphocytes of MHS swine, but had no significant effect on lymphocytes from control swine (225.0 +/- 91.4; P less than 0.01). Exposure to 2 mmol/L halothane resulted in a 6-fold increase of free calcium concentration to 255.9 +/- 91.4 nmol/L in lymphocytes from MHS swine and a 63% increase in lymphocytes from controls (303.8 +/- 116). The rate of halothane-induced increase in cytosolic calcium was 13 times greater in lymphocytes from MHS swine, compared with controls. These data indicated that the molecular defect that results in halothane-hypersensitivity and is characteristic of muscle of MHS swine also occurs in lymphocytes from MHS swine.
Serum bile acid (SBA) reference intervals were established by use of a radioimmunoassay method for fasting dogs to be 0.2 to 4.3 micro mol/L (n = 60) and for 2 hour postprandial samples to be 0.6 to 24.2 micro mol/L (n = 37). The SBA reference intervals estimated using an enzymatic method were 0 to 8.6 micro mol/L for fasting (n = 26) and 0 to 29.8 micro mol/L for 2 hour postprandial samples (n = 36). The correlation between the two methods including samples from healthy dogs and clinical cases is good (n = 128, r = 0.82, p < 0.0001). The radioimmunoassay method is linear to 50 micro mol/L and the enzymatic method is linear to 100 micro mol/L, thus both methods require serum dilutions to be made in many cases of primary liver disease. The enzymatic method is less expensive and more convenient for use in a clinical laboratory but requires a greater sample volume (400 micro I) than the RIA method (50 micro I). Both methods have adequate precision and accuracy to be useful as diagnostic tests of liver function in dogs.
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Cytotoxic and hemolytic activity of Haemophilus (Actinobacillus) pleuropneumoniae serotype 1 strain CM5 was investigated because of the potential role as a virulence determinant. Viable bacteria were toxic for porcine and bovine neutrophils, whereas bacteria killed by heat treatment at 60 C for 1 hour were not. Similarly, bacteria-free culture supernatant was cytotoxic and hemolytic in assays that used porcine neutrophils and erythrocytes, whereas supernatant treated at 60 C for 1 hour had no activity. Erythrocytes from various species were susceptible to the hemolytic activity of bacteria-free culture supernatant, with ovine and bovine erythrocytes being most sensitive. The neutrophil-toxic and hemolytic activity of bacteria-free culture supernatant was inhibited by cholesterol and oxygen and abolished after trypsin digestion. The neutrophil-toxic and hemolytic activity was preserved during storage at or less than 4 C, but was lost rapidly at 56 C or 80 C. Neutralizing antibodies were demonstrated in serum of pigs and rabbits immunized with 10-fold concentrated culture supernatant of strain CM5 and in field pigs that had recovered from natural infection with H pleuropneumoniae serotype 1. Bacteria-free culture supernatants of 18 strains, including H pleuropneumoniae serotypes 1 through 10, Actinobacillus suis, and Haemophilus taxon minor group, were tested for heat-sensitive, neutrophil-toxic, and hemolytic activity. Fifteen strains were neutrophil toxic, but only 10 of these were hemolytic. Haemophilus pleuropneumoniae, serotype 1, strain VLS557; serotype 5, strain K17; and Haemophilus taxon minor group strain 33PN were neither cytotoxic nor hemolytic.
In vitro neutrophil adherence, random migration, chemotaxis, resting and phagocytosis-associated oxygen consumption and bactericidal responses were assessed in sheep experimentally infected with bovine leukemia virus (BLV). Neutrophil function was examined in two groups of 9 control and 9 BLV-infected sheep at 0, 1, 2, 3, 5, 7, 11 and 15 weeks post-infection. Enhanced neutrophil adherence, chemotaxis and resting oxygen consumption responses were found in the infected group at 2, 11 and 15 weeks respectively. Significant alterations between groups were not demonstrated during the other time intervals.
In the fall of 1983, 322 western calves, in five different groups, were bled on arrival at two Ontario feedlots. Calves receiving treatment for respiratory disease, within 35 days of arrival, were denoted as cases. The hematology and serum chemistry parameters of cases were compared to those of controls. Cases had significantly (p less than 0.05) lower hematocrits, fewer platelets, and more band cells on arrival, than did controls. Cases also had lower serum phosphorous, magnesium, potassium, iron and alkaline phosphatase levels, and increased bilirubin and aspartate aminotransferase levels relative to controls. Based on the results of multivariable logistic regression, hematocrit, platelet numbers, serum phosphorous, iron and aspartate aminotransferase levels were the most significant parameters for the prediction of respiratory disease. Reference values for stressed feedlot calves were created. Most parameters were distributed in an approximately normal manner, however the group to group variation in most parameters was significant.
Neutrophils were isolated from the peripheral blood of adult equids (group 1) and were purified on a density gradient of polyvinylpyrrolidone-coated silica gel. A bactericidal assay was developed, using an equine skin isolate of Staphylococcus epidermidis as target bacterium in medium containing pooled fresh equine serum for opsonization. Significant (P less than 0.05) killing was observed after 60 or 120 minutes' incubation. Reduction in bactericidal function of blood neutrophils was not found after incubation with a virulent strain of Mycoplasma felis for 30 or 60 minutes. Similarly, the function of blood and pleural neutrophils of ponies with M felis-induced pleuritis (group 2) was not different from the function of similar neutrophils from sham-inoculated control ponies (group 3). The number of viable M felis organisms was markedly reduced in the presence of fresh equine serum and equine-specific antibodies, but not when the serum was heat inactivated. Equine neutrophils did not phagocytize M felis. Seemingly, M felis did not impair bactericidal activity of equine neutrophils. Therefore, this mechanism does not predispose equids to bacterial pleuritis.