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Biomedical subjects

J P Braun

Publications and source records attributed to J P Braun.

At least 19 recordsLinked to original sources

The accuracy of the i-STAT portable analyser for measuring blood gases and pH in whole-blood samples from dogs.

To assess the suitability of the i-STAT portable analyser for use by non-laboratory personnel, we measured blood gases and pH in venous blood samples from 100 dogs. Deming's regression and bias plots were used to compare i-STAT results with those obtained by laboratory professionals using two different autocalibrated benchtop analysers. Overall accuracy of the portable analyser proved excellent for pH, pO(2), and pCO(2) (r=0.978, 0.968 and 0.997, respectively), with Deming's regression slopes close to 1.00 (0.96, 0.97 and 1.08 for pH, pO(2), and pCO(2), respectively) and intercepts close to zero (0.28, 0.47 kPa and 0.46 kPa for pH, pO(2), and pCO(2), respectively). The accuracy of the i-STAT was also satisfactory for calculated parameters: bicarbonates, total CO(2), base excess and oxygen saturation. Our findings show this portable analyser to be a valid substitute for expensive benchtop analysers in situations requiring mobility, or when small numbers of tests are to be performed by users not specialized in laboratory techniques.

Animals↗

Exercise does not induce major changes in plasma muscle enzymes, creatinine, glucose and total proteins concentrations in untrained beagle dogs.

Changes in plasma creatinine (Pl-Creat), glucose, total proteins (Pl-TP), creatine kinase (Pl-CK), lactate dehydrogenase, aspartate aminotransferase and packed cell volume were evaluated in untrained Beagle dogs before, during and after a 60 min race at an average speed of 9 km/h. There was no major effect of exercise on those parameters except, when phases are compared, a slight increase of Pl-TP during exercise (max. + 6.4%), a moderate but after exercise (delayed increase of Pl-CK max. + 245%) and a slight decrease of Pl-Creat after exercise (max. -9.6%). It was therefore concluded that strenuous exercise in sedentary dogs did not induce major variations in any of routine plasma variables measured and would not lead to clinically relevant misinterpretation. However, for Pl-CK, the interpretation of repeated measures may be misleading if two samples are collected in the same animal before and after exercise.

Animals↗

Passive containment and reverse remodeling by a novel textile cardiac support device.

BACKGROUND: Progressive remodeling and dilation of cardiac chambers is responsible in part for myocardial dysfunction in chronic heart failure. Preclinical studies with suitable animal models indicate that a passive cardiac constraint device can promote reverse remodeling, with improvement in cardiac function. We hypothesize that such a device could provide benefit for stable heart failure patients in New York Heart Association (NYHA) class II and III. METHODS AND RESULTS: From April 1999 to March 2000, 27 patients received Acorn's Cardiac Support Device (CSD) during an initial safety/feasibility study. In 11 patients, the only surgical measure was CSD placement. Most patients suffered from idiopathic cardiomyopathy; 4 were in NYHA class II, one was in class II/III, and 6 were in class III. All were stable on intensive medical treatment. The CSD, a textile polyester device, was fitted snugly around the heart during surgery. All patients survived surgery and recovered smoothly. Three months after surgery, 56% of patients were in NYHA class I, 33% were in class II, and 11% were in class II/III. Echocardiography showed an improvement in left ventricular ejection fraction from an average of 22% to 28% and 33% at 3 and 6 months, respectively. Simultaneously, the left ventricular end-diastolic dimension decreased from 74 mm to 68 mm and 65 mm, respectively. Mitral valve regurgitation (on a scale of 0 to 4+) decreased from 1.3 to 0.7 by 3 months. Quality-of-life indices correlated with the apparent reversal of ventricular remodeling. Preoperative cardiac medications remained virtually unchanged after implant. CONCLUSIONS: In the short- and intermediate-term, CSD implantation seems to ameliorate symptoms and improve cardiac and functional performance in heart failure patients. Worldwide randomized trials are currently underway.

Adult↗

Plasma fibrinogen measurement in the horse: comparison of Millar's technique with a chronometric technique and the QBC-Vet Autoreader.

Plasma fibrinogen is widely used in horse practice as an unspecific positive marker of inflammatory diseases; it is also lowered in disseminated intravascular coagulation. Three fibrinogen measurement methods--Millar's heat-denaturation in a microhaematocrit tube, automated reader for heat-denaturation, and chronometric measurement of clot formation after addition of excess thrombin-were compared by means of Passing-Bablock's regression and Bland-Altman difference plots, in blood plasma of 30 clinically healthy and 57 diseased horses. Correlations between the three techniques were excellent (r >0.92). The two heat-denaturation techniques correlated very closely up to 6 g l(-1), above which the results obtained by Millar's technique started to fall below those obtained by the automatic reader. There was proportional bias between Millar's technique and the chronometric technique, with the latter producing results some 30% lower, indicating that reference intervals and decision limits should be adapted accordingly.

Animals↗

Use of plasma creatine kinase pharmacokinetics to estimate the amount of excercise-induced muscle damage in Beagles.

OBJECTIVE: To assess the effects of moderate exercise on plasma creatine kinase (CK) pharmacokinetics and to estimate exercise-induced muscle damage in dogs. ANIMALS: 6 untrained adult Beagles. PROCEDURE: The study was divided into 3 phases. In phase 1, dogs ran for 1 hour at a speed of 9 km/h, and samples were used to determine the area under the plasma CK activity versus time curve (AUC) induced by exercise. In phases 2 and 3, pharmacokinetics of CK were calculated in dogs during exercise and at rest, respectively. Values for AUC and plasma clearance (CI) were used to estimate muscle damage. RESULTS: At rest, values for Cl, steady-state volume of distribution (Vdss), and mean retention time (MRT) were 0.32+/-0.02 ml/kg of body weight/min, 57+/-173 ml/kg, and 3.0+/-0.57 h, respectively. During exercise, Cl decreased significantly (0.26+/-0.03 ml/kg/min), MRT increased significantly, (4.4+/-0.97 h), and Vdss remained unchanged. Peak of plasma CK activity (151+/-58.8 U/L) was observed 3 hours after completion of exercise. Estimated equivalent amount of muscle corresponding to the quantity of CK released was 41+/-29.3 mg/kg. CONCLUSION AND CLINICAL RELEVANCE: These results revealed that exercise had a minor effect on CK disposition and that the equivalent amount of muscle damaged by moderate exercise was negligible. This study illustrates the relevance for use of the minimally invasive and quantitative pharmacokinetic approach when estimating muscle damage.

Animals↗

Comparison of four methods for determination of total protein concentrations in pleural and peritoneal fluid from dogs.

OBJECTIVE: To compare 4 techniques for determination of total protein concentrations in peritoneal and pleural effusions from dogs. SAMPLE POPULATION: 23 peritoneal and 12 pleural fluid samples from 35 dogs with various abnormalities. PROCEDURE: Samples were collected into tubes containing EDTA, centrifuged, and stored at -20 C until total protein concentrations were assessed. Protein concentration in each sample was determined by use of urine test strips, refractometry, and Bradford and biuret techniques. Accuracy of each method was determined, using dilutions of human control sera. RESULTS: There was good correlation among results of all quantitative procedures. Results of the biuret technique were more accurate than results of the Bradford assay. Refractometry underestimated protein concentration in samples with < 20 g of protein/L. Results of urine test strips correctly classified effusion samples into 2 groups on the basis of total protein concentrations less than or greater than 20 g/L. CONCLUSIONS AND CLINICAL RELEVANCE: Results of any of these 4 techniques can be used to rapidly and efficiently differentiate peritoneal and pleural fluid from dogs into transudates and exudates on the basis of total protein concentration less than or greater than 20 g/L, respectively.

Animals↗

Differential effects of phenobarbital on the constitutive and inducible expression of P450 2B and 3A subfamilies in sheep tissues.

The activity and expression of cytochromes P450 were determined in liver, kidneys, lungs, duodenum, jejunum, ileum, and caecum of adult Lacaune sheep. High expression of total P450, benzphetamine and erythromycin demethylase activities, and P450 2B isoforms, as two distinct proteins that were detected and called P4502 Bm and P4502 Bx, was found in the lungs (in addition to liver). By contrast, the P450 3A subfamily was only expressed in liver and duodenal mucosa of untreated sheep. Phenobarbital (PB) treatment led to significant increases in all measured hepatic parameters and in total P450 of each investigated organ with the exception of ileum and caecum. Benzphetamine demethylase activity increased in liver and kidneys, correlating with the expression of the two P450 2B proteins, which were also induced in duodenum and ileum. By contrast, benzphetamine demethylase activity and expression of the P450 2B isoforms in lungs were unchanged by PB treatment. Erythromycin demethylation activity and P450 3A subfamily expression was increased only in liver of PB-treated sheep.

Animals↗

Overestimation of the predictive value of positives by the usual calculations of the specificity of diagnostic tests.

The specificity of a diagnostic test for a given disease, i.e. the percentage of true negatives, can be calculated from either the results from a group of healthy animals or possibly from a group which also contains diseased animals which are free of the particular disease for which the test has been performed. The specificity may be much lower in the latter case and the predictive value of positives thus greatly reduced. In the example of creatine kinase being used for the diagnosis of muscle diseases in dogs, the specificity at the thresholds of 105 and 150 U/L (upper limits of the 95% and 99.7% interquantiles) decreased from 0.98 and 1.0 to 0.66 and 0.78, respectively.

Animals↗

The effect of experimental renal failure on tolfenamic acid disposition in the dog.

The pharmacokinetic disposition of tolfenamic acid, an NSAID, after a single administration of tolfenamic acid (4 mg kg(-1)) by the intravenous (IV) route was compared in eight dogs before and after a surgically induced renal failure. Renal impairment was confirmed by a significant increase (p <0.001) of water intake, urine volume, and urea and creatinine plasma concentration. PAH and inulin clearances decreased after surgery from 15.2 +/- 4.2 to 9.5 +/- 0.8 mL kg(-1) min(-1) (p < 0.05) and from 4.37 +/- 1.15 to 2.43 +/- 0.88 mL kg(-1) min(-1) (p=0.067),respectively. After surgery, clearance of TA was significantly (p <0.001) increased, from 2.22 +/- 1.68 to 3.59 +/- 1.81 mL kg (-1) min(-1). There was no modification of the steady-state volume of distribution (p > 0.05) and the mean residence time was significantly decreased from 606 +/- 199 to 373 +/- 302 min (p < 0.05). No variation of binding to plasma proteins (> or = 99%) was observed. These results suggest that renal insufficiency could increase hepatic metabolism and/or alter the enterohepatic cycle of TA.

Acute Kidney Injury↗

In vivo quantification of muscle damage in dogs after general anaesthesia with halothane and propofol.

Muscle damage in dogs anaesthetised with halothane and propofol was quantified by measurement of the area under the curve of plasma creatine kinase (CK) versus time. Plasma CK remained unchanged during anaesthesia for two and a half and five hours. Following halothane anaesthesia of dogs (resting on one side directly on the surgical table or on cushions, and with or without rotation of the body every 30 minutes), plasma CK was elevated in some animals to 10,000 U/litre by the 12th hour (baseline value < or = 100 u/litre), whereas it remained almost unchanged in other animals. Plasma CK then returned to reference values on day 2 or 3. The mean equivalent of muscle damaged ranged from 0.6 to 0.9 g/kg bodyweight. No muscle damage could be demonstrated in animals anaesthetised with propofol. It is therefore concluded that plasma CK should not be used as a diagnostic aid following halothane anaesthesia because of false positives due to the halothane anaesthesia itself and that propofol is best suited for the investigation of muscle damage due to surgical procedures.

Anesthesia, General↗

Non-invasive and quantitative evaluation of post-injection muscle damage by pharmacokinetic analysis of creatine kinase release.

Intramuscular administration of veterinary drugs can induce severe muscle damage resulting in economic losses and residue persistence. Local tolerance is usually evaluated by macroscopic examination of the injection site requiring euthanasia of a large number of animals. A non-invasive quantitative method, based on the pharmacokinetic analysis of creatine kinase (CK) release from muscle, is proposed for the evaluation of post-injection muscle damage. Plasma CK activity is a specific and sensitive marker of skeletal muscle damage. Three disposition parameters are needed to measure the actual amount of CK released by the injured muscle: plasma CK clearance, bioavailability of CK from muscle and area under the plasma CK activity vs time curve. A CK solution from a homologous muscle extract was administered in different animal species by intravenous route and by intramuscular route for the determination of the CK disposition parameters. The general equation for the determination of the destroyed muscle equivalent (Q), following the drug intramuscular injection, is: Q = CI x AUC/F x M, with Cl, the plasma CK clearance; AUC, the area under the plasma CK vs time curve after drug administration; F, the CK bioavailability from muscle; and M, the CK content in the injected muscle. Population equations are proposed for dogs, sheep, horses and cattle and their use is illustrated. Rabbits and pigs seem inappropriate species for the pharmacokinetic approach because of stress-induced spontaneous increases in plasma CK. In cattle, for example, Q (g.kg-1 body weight) = 4.4 x 10(-6) AUC (U.h.L-1) and the estimated equivalent of muscle destroyed after a single IM injection of a chloramphenicol formulation was about 300 g. This screening approach is simple, ethical, rapid and inexpensive.

Animals↗

Disposition of creatine kinase activity in dog plasma following intravenous and intramuscular injection of skeletal muscle homogenates.

The fate of skeletal muscle-derived creatine kinase (CK) was investigated in six dogs. After i.m. and i.v. injections of 3000 g and 105,000 g supernatants of dog muscle homogenates, plasma CK activity was measured up to 48 h. There was no significant difference in pharmacokinetic parameters dependent on the type of supernatant injected. After i.v. injection, the volume of distribution of CK was equal to the plasma volume, CK clearance was relatively low (about 0.5 mL/kg/min) and its terminal half-life of elimination was about 2.5 h. After i.m. injection, the CK terminal half-life was about 6.5 h, demonstrating a flip-flop mechanism, i.e. a limiting absorption process from the site of injection. Bioavailability after i.m. injection was about 65%, and the rate of absorption from muscle injection site was relatively slow: peak activity occurred at the second hour post administration, and most CK activity had been absorbed by 24 h. These pharmacokinetic parameters can be used as a basis for a minimally invasive means of quantitating muscle damage either after intramuscular drug administration or in canine sports medicine.

Analysis of Variance↗

A non-invasive and quantitative method for the study of tissue injury caused by intramuscular injection of drugs in horses.

The present study was undertaken to measure the weight of muscle destroyed by an intramuscular injection of phenylbutazone (PBZ) in horses. In six horses, CK disposition parameters were evaluated after intravenous (i.v.) and intramuscular (i.m.) administration of a CK horse preparation. The same horses received PBZ, a potentially irritating agent, by i.v. and i.m. (neck and hindquarter) routes. Data were analysed using compartmental approaches and instantaneous CK flux was calculated using a discrete deconvolution method. For a 150 U/kg CK dose, the steady-state volume of distribution was 0.050 +/- 0.0115 L/kg and the plasma half-life was 112 +/- 18 min. After CK i.m. administration, the half-life of the terminal phase was 11.8 +/- 5.3 h indicating a flip-flop process and the mean bioavailability of CK was close to 100%. After PBZ i.m. administration, the CK activity was significantly increased with peak values of 508 +/- 109 U/L after the neck administration and 873 +/- 365 U/L after the gluteal administration. By measuring the total amount of CK released from injured muscle, it was calculated that an equivalent of 0.044 +/- 0.029 g/kg of muscle was destroyed after PBZ administration in the neck. The corresponding figure was 0.118 +/- 0.048 g/kg after intragluteal PBZ administration. By deconvoluting plasma CK activity, it was shown that the CK entry rate was maximum for the first 30-60 min following PBZ administration, which then decreased slowly to return to the control value after a delay of 24-48 h after PBZ administration. It was concluded that the CK release pattern following a controlled muscular damage was a non-invasive approach useful for quantifying the amount of damaged muscle, and that the calculation of CK input rate by deconvolution was of potential interest in describing events at the muscle cell level.

Animals↗

In vivo non-invasive quantification of muscle damage following a single intramuscular injection of phenylbutazone in sheep.

Intramuscular drug administration can lead to more or less extensive muscle damage. The aim of the present study was to show the possibility of quantitating, in vivo and non-invasively, the equivalence of muscle destroyed by the administration of a test drug (phenylbutazone) known for its injurious properties. Creatine kinase (CK) kinetic parameters (clearance, volume of distribution) were measured in 6 sheep after an iv administration of muscle CK homogenate. In the same 6 sheep, CK release after iv and im 8 mg phenylbutazone/kg was measured. The calculated total CK released, based on the CK plasma clearance (0.28 mL/kg/min) and area under the curve of CK activity after im phenylbutazone administration was 191 +/- 140 U/kg. By relating this quantity to that of CK gluteal muscle (5114 +/- 891 U/g), it was calculated that im phenylbutazone administration was able to destroy an equivalence of 2.4 +/- 2.1 g of muscle. For the 2 main sites of im administration (neck and gluteal muscle), general equations are proposed to calculate the equivalence of muscle destroyed in sheep when only plasma CK activity following a test drug administration is available.

Animals↗

Creatine kinase in dog plasma: preanalytical factors of variation, reference values and diagnostic significance.

In the dog, plasma creatine kinase (CK) activity was stable up to one week at +4 degrees C and one month at -20 degrees C. Activity was higher in serum than in plasma due to interference by CK from the platelets. The reference values were determined in 232 dogs using the IFCC recommended method. There was a significant decrease in activity with age but no effect of sex. In adults, plasma CK exhibited a log-normal distribution ranging from 20 to 104 U per litre. In 510 dogs with various diseases, the overall sensitivity and specificity of CK determination were 40 per cent and 98 per cent, respectively. The numerous false negatives could result from the relatively short half-life of the enzyme, while the false positives could be due to secondary muscle damage.

Animals↗

Kinetic evaluation of muscle damage during exercise by calculation of amount of creatine kinase released.

To quantify the extent of muscle alteration during prolonged exercise, the release rate of creatine kinase (CK) from striated muscle was measured in six horses during a rest period (6 h) and during three exercise tests (15, 30, and 60 km) at a constant speed of 200 m/min. CK clearance was measured after intravenous bolus administration (150 U/kg) of a CK solution obtained from horse muscle. The CK steady-state volume of distribution was 0.059 +/- 0.0215 l/kg, the terminal half-life was 123 +/- 28 min, and the plasma clearance was 0.36 +/- 0.10 ml.kg-1 x min-1. After an intramuscular CK administration, the CK systemic availability was 74.1 +/- 21.2% and the half time of absorption was 9.4 +/- 5.7 h, indicating a slow process for CK transit through the lymphatic system. The CK release rate was only significantly increased during the 60-km exercise test. The increase of CK plasma activity was observed after a delay of approximately 5 h and peaked after the end of the race; the estimated CK release rate was 9.92 +/- 2.62 U.kg-1 x h-1 over a mean duration period of 65.8 +/- 15.8 h. With the CK activity of horse striated muscle taken into account, a 60-km race released a quantity of CK corresponding to an equivalent of 18.8 +/- 4.3 g striated muscle. It is concluded that the equivalent amount of damaged muscle may be considered as negligible for a 60-km test and that only very high plasma CK activity levels (at least higher than 10,000 U/l) may provide some evidence of a myolysis.

Animals↗

Serum chemistry values for Arabian sand gazelles (Gazella subgutturosa marica).

Values for urea, creatinine, glucose, total bilirubin, sodium, potassium, chloride, calcium, phosphates, magnesium, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, lactate deshydrogenase, and creatine-kinase are reported for the first time for 32 sand gazelles (Gazella subgutturosa marica) in Saudi Arabia. Comparisons were made between two groups: one sampled before a trip and the other sampled after a 14 hr trip. Only aspartate aminotransferase was higher in the second group; magnesium and phosphates were lower in that group.

Animals↗

Pharmacokinetic variables and bioavailability from muscle of creatine kinase in cattle.

Pharmacokinetic variables of skeletal muscle creatine kinase (CK) activity after IV administration of a muscle extract; CK bioavailability after IM administration of the muscle extract; and effect of IM administration of saline solution, to appreciate the possible release of CK consecutive to muscle puncture, were determined in 6 cows. A general equation for the quantitative estimation of skeletal muscle damage also was derived. Administration of saline solution IM had no effect on plasma CK activity (ANOVA, P > 0.05) in any of the cows. After IV administration of the muscle extract (150 U/kg of body weight), mean volume of the central compartment, plasma half-life, and plasma clearance of CK were 0.027 +/- 0.007 L/kg, 520 +/- 109 minutes, and 6.43 +/- 2.29 ml/kg/h, respectively. After IM administration (150 U/kg), mean bioavailability of CK was 51 +/- 17% and maximal plasma CK activity (500 +/- 97 U/L) was observed at 454 +/- 131 minutes. The rate of CK activity entry into plasma was determined by use of deconvolution analysis. Two peaks were observed; the first appeared before the 30th minute after IM administration, and the second appeared at 3.3 +/- 1.1 hours. Amplitudes were 6.31 +/- 4.45 and 6.57 +/- 3.08 U/kg/h, for the first and the second peaks, respectively. The quantity of CK liberated from control muscle was 0.69 +/- 0.12 U/kg/h, corresponding to a normal daily catabolism of 5.8 +/- 1.0 mg of muscle/kg.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗