Knee joint accessory motion following anterior cruciate ligament allograft reconstruction: a preliminary report.

Early in the postoperative period, changes in tibial translation have been noted in patient populations following anterior cruciate ligament reconstructive surgery. Deformation due to a lengthening of the ligament graft has been the most widely accepted reason for the change in tibial translation. Treatment techniques have not been proven successful in the abatement or reversal of this graft lengthening. The purpose of this study was to investigate the effect of functional bracing on tibial translation during the first year postoperatively in a group of patients with early changes in tibial translation. Three consecutive patients with early increases in KT-2000 manual maximum total drawer following bone-patellar tendon-bone allograft reconstruction were identified as subjects in the control group. Five consecutive anterior cruciate ligament bone-patellar tendon-bone allografts with early increases in KT-2000 manual maximum total drawer were identified as subjects in the treatment group. These patients were followed monthly during the first year postoperatively by manual maximum total drawer KT-2000 testing. Criteria for inclusion in the treatment and control groups included KT-2000 testing, with an increase in translation of greater than or equal to 2 mm when compared with the uninvolved knee during the first year postoperatively. The treatment group was required to wear a functional knee brace during all weight-bearing activities until KT-2000 displacement measures were stabilized for 3 consecutive months. Treatment with the functional brace resulted in a mean 2.3-mm decrease in tibial translation in the manual maximum total drawer KT-2000 when comparing the involved and uninvolved knee prebracing with posttreatment. All five subjects in the treatment group had a decrease in tibial translation. A Median Test comparing the control and treatment group's KT-2000 scores was significant at the p < .05 level. Patients who experience early increases in tibial translation with anterior cruciate ligament reconstructions may be assisted in a reduction of the displacement by the use of a functional brace.

A measurement of anterior tibial displacement in the closed and open kinetic chain.

Anterior displacement of the tibia during knee extension movement has been identified as a possible factor in anterior cruciate ligament (ACL) reconstruction failure due to the increased stress placed on the graft, leading to a creep response in the healing graft. Nineteen healthy subjects with a unilateral ACL deficiency were evaluated in an open and closed kinetic chain. A KT-1000 was used to measure anterior displacement of the tibia on the femur during isometric open and closed kinetic chain exercise at 30 and 60 degrees. An analysis of variance for repeated measures followed by Newman-Keuls multiple comparison tests were performed to determine the differences between the open and closed kinetic chain for the involved and uninvolved knee. Statistically significant differences were found when comparing the amount of anterior displacement between the open and closed kinetic chain for the involved and uninvolved knee at 30 and 60 degrees. Clinicians utilizing isometric exercise in rehabilitation of the anterior-cruciate-deficient and the anterior-cruciate-reconstructed patient should be aware of the increased amount of anterior tibial displacement when comparing open and closed kinetic chain exercise.

Antipyrine and caffeine dispositions in clinically normal dogs and dogs with progressive liver disease.

Dispositions of caffeine and antipyrine were compared as indicators of decreasing hepatic function in dogs with experimentally induced progressive liver disease. Dimethylnitrosamine, a hepatospecific toxin, was administered orally to 16 dogs; 6 dogs served as controls (group 1). Three classes of liver disease were defined by histologic features: mild (group 2; n = 5), moderate (group 3; n = 6), and severe (group 4; n = 5). Disposition of antipyrine, and 24 hours later, caffeine was studied 3 weeks after the last dose of toxin in each dog. For both drugs, rapid IV administration of 20 mg/kg of body weight was administered and serum samples were obtained at intervals for determination of at least 5 terminal-phase drug half-lives. For both drugs, clearance and mean residence time differed among groups (P < or = 0.01). Clearance of antipyrine and caffeine was decreased in groups 3 and 4, compared with groups 1 and 2. Antipyrine and caffeine mean residence times were longer in group-3 dogs, compared with dogs of groups 1 and 2. Correction of caffeine and antipyrine clearances for hepatic weight increased discrimination between groups 3 and 4. The clearance and mean residence time ratios of antipyrine to caffeine were calculated for each group and, when compared with values for group-1 dogs, were used to test for differences between the 2 drugs in response to disease. Ratios did not differ among groups. These results indicate that the disposition of antipyrine and caffeine may change similarly with progression of dimethylnitrosamine-induced liver disease.

Measurement of hippocampal levels of cellular second messengers following in situ freezing.

The in situ freezing technique has been widely used to fix labile metabolites and cellular second messengers in cerebral cortex. In this study, we isolated specific brain regions at 0 degree C from coronal sections of frozen heads following in situ brain freezing and measured regional concentrations of labile metabolites and cellular messengers. These levels in the cortex were compared with those in cortical punches obtained at freezing temperature (less than -40 degrees C) from the same in situ frozen brains and those of cortex dissected from decapitated animals. In both isoflurane- and pentobarbital-anesthetized animals, we observed that the levels of lactate, free fatty acids, inositol 1,4,5-trisphosphate, and diacylglycerol, as well as the proportion of protein kinase C associated with the membrane fraction, were similar in cortical punches taken at freezing temperature and those dissected at 0 degree C. However, with animals decapitated at room temperature, cortical and hippocampal levels of lactate, free fatty acids, and inositol 1,4,5-trisphosphate and the proportion of membrane protein kinase C were significantly higher than those of corresponding brain regions isolated at 0 degree C from in situ frozen brains (p < 0.05). These results indicate that dissection of cortex and hippocampus at 0 degree C following in situ freezing will eliminate decapitation-induced production of artifacts and changes in the levels of cellular second messengers such as inositol 1,4,5-trisphosphate, diacylglycerol, and protein kinase C. The present technique, used in conjunction with in situ freezing, will fix cellular second messengers and labile metabolites in several regions of brain and may facilitate accurate characterization of molecular and cellular mechanisms underlying CNS function.

Indocyanine green disposition in healthy dogs and dogs with mild, moderate, or severe dimethylnitrosamine-induced hepatic disease.

Disposition kinetics of indocyanine green (ICG) were used to evaluate hepatic function in healthy Beagles (group 1; n = 6) and Beagles with progressive hepatic disease induced by oral administration of dimethylnitrosamine, a hepatospecific toxin. Three classes of hepatic disease were defined by histologic features: mild (group 2; n = 5), moderate (group 3; n = 6), and severe (group 4; n = 5). Disposition of ICG was studied 3 weeks following the last dose of toxin. A rapid IV injection of 0.5 mg of ICG/kg was administered and serum samples were obtained at certain intervals during 60-minute periods. Serum ICG was analyzed by use of visible spectrophotometry. Disposition kinetics were determined from serum ICG concentrations vs 15- and 60-minute time curves and compared between one another and among groups. Data based on 60-minute time curves were not significantly different from those based on 15-minute curves. Area under the curve for ICG was greatest in group 3. Clearance of ICG was decreased and mean resident time was increased in groups 3 and 4, compared with those in groups 1 and 2. When disposition data (60 minutes) were normalized for differences in hepatic weight among dogs, group-3 mean resident time was significantly greater than that of group 4. This study supports the diagnostic benefits of using ICG disposition kinetics as a method of evaluating hepatic function in dogs with progressive liver disease.

Dimethylnitrosamine-induced hepatotoxicosis in dogs as a model of progressive canine hepatic disease.

A model of toxin-induced progressive hepatitis is described in Beagles. The toxin, dimethylnitrosamine, was administered orally to 18 Beagles; 6 dogs comprised a control group. Clinical signs and laboratory test results were monitored as disease progressed and were used to determine the end point of disease. Following euthanasia, histologic lesions were scored and used to derive a total severity score for each dog. Severity scores were then used to allot the 18 dogs to 3 groups of hepatic disease, defined as mild, moderate, or severe. Changes in clinical laboratory test results, including tests of hepatic function, and clinical signs indicative of liver disease were described chronologically for all dogs. Group means of clinical laboratory test results and quantifiable clinical signs (eg, weight loss and ascitic fluid accumulation) were compared. This model offers several advantages, compared with other experimental models of canine hepatic disease. These include hepatospecificity, similarity to natural disease (eg, the development of multiple extrahepatic portosystemic shunts), and the ability to titrate the disease to a desired end point. The major disadvantages of this model were the toxic nature of the drug to human beings and the variation in individual animal response to the toxin, which precludes preassignment of animals into groups.

Induction of peroxisomal acyl CoA oxidase activity and lipid peroxidation in primary rat hepatocyte cultures.

Peroxisome proliferators have been suggested to induce liver carcinogenesis as a result of increased peroxisomal hydrogen peroxide production and cellular oxidative stress. Primary monolayer cultures of hepatocytes isolated from male F344 rats were incubated in medium containing one of three different peroxisome proliferators and examined for the induction of peroxisomal CoA oxidase activity and lipid peroxidation. The latter parameter was determined by measuring levels of conjugated dienes in lipid fractions extracted from harvested cells. The peroxisome proliferators used in these studies were nafenopin and clofibric acid (two hypolipidemic drugs) and mono(2-ethylhexyl)phthalate (MEHP), the primary metabolite of the industrial plasticizer, di(2-ethylhexyl)phthalate (DEHP). The relative specific activity of peroxisomal acyl CoA oxidase was increased by about 300% after incubation for 44 h with 200 microM nafenopin; lower levels of induction were observed with clofibric acid or MEHP. Relative to controls, the level of conjugated dienes was increased approximately 2-fold after incubation with 200 microM nafenopin; there was no apparent increase in conjugated dienes after incubation with up to 200 microM MEHP or 400 microM clofibric acid. The increase in conjugated dienes with 200 microM nafenopin was inhibited by co-incubation with the antioxidant, N,N'-diphenyl-p-phenylenediamine. Thus, peroxisomal enzyme induction by nafenopin can result in membrane lipid peroxidation and monolayer cultures of rat hepatocytes may provide a useful model system for studying relationships between peroxisome proliferation, enhanced hydrogen peroxide production and cellular changes due to hepatic oxidative stress.

Comparative metabolism and genotoxicity of the structurally similar nitrophenylenediamine dyes, HC Blue 1 and HC Blue 2, in mouse hepatocytes.

Previous studies indicated that HC Blue 1 induced heptocellular carcinomas in B6C3F1 mice whereas the structurally similar nitroaromatic amine HC Blue 2 did not. In an attempt to elucidate the biochemical mechanisms responsible for their different carcinogenic potencies, comparative metabolism and genetic toxicity studies were undertaken. Eighteen-hour urinary recovery of administered radioactivity was equivalent for both compounds following oral gavage (100 mg/kg) in female B6C3F1 mice. By HPLC analysis, HC Blue 1 yielded 3 major polar metabolite peaks, one of which was susceptible to glucuronidase. In vivo metabolism of HC Blue 2 yielded a single major metabolite peak which was not hydrolyzed by glucuronidase. Metabolism by B6C3F1 mouse hepatocytes yielded metabolite profiles which were qualitatively similar to the profiles observed after in vivo metabolism. HC Blue 1 was metabolized by hepatocytes at approximately twice the rate of HC Blue 2. Cytogenetic evaluations of mouse hepatocytes after in vitro treatment indicated HC Blue 1 was more potent than HC Blue 2 in inducing chromosomal aberrations while both chemicals showed weak activity for inducing sister-chromatid exchanges. Furthermore, in the V79 cell metabolic cooperation assay, HC Blue 1, but not HC Blue 2, inhibited cell-to-cell communication suggesting a non-genotoxic activity may be present for HC Blue 1. It is concluded that qualitative and quantitative differences exist in the metabolism of these compounds and that genotoxic as well as nongenotoxic effects may contribute to their different carcinogenic potencies.

Effect of weight loading on the coronary band interstitial fluid pressure in horses.

Interstitial fluid pressures, as a possible function of limb load, were measured at 2 sites within the digital coronary dermis of both cranial digits in 10 standing horses. Fluid pressure changes and digital load measurements were simultaneously detected and recorded by use of, respectively, modified wick-in-needle and force plate transducers coupled to a microcomputer. Mean pressures, recorded at limb loads between 50 and 80 kg, were 2.29 +/- 3.17 mm of Hg at the toe and 2.49 +/- 5.91 mm of Hg at the heel. Mean pressures, recorded between 150 and 180 kg, were 5.01 +/- 5.23 mm of Hg at the toe and 1.28 +/- 7.69 mm of Hg at the heel. These data indicate that, in the static limb, no statistically significant change in interstitial fluid pressure occurs at loads up to 180 kg.

Postpartum reproductive performance in the multiparous mare fed to obesity.

Twenty multiparous Quarter Horse mares were assigned to one of two treatment groups at 40 to 75 d of pregnancy. Group 1 was the control group and the mares were fed to maintain a moderate degree of body fat (condition score 5.5 to 7). Group 2 was the obese group and the mares were fed to achieve (prepartum) and then maintain (post partum) an extremely high degree of body fat (condition score 9). Estrous intensity was evaluated using subjective teasing scores ranging from 0 (rejection) to 4 (maximum receptivity). Mares were artificially inseminated beginning with the second postpartum ovulatory cycle; the study was terminated after 63 d of pregnancy. Duration of estrus, maximum teasing score and the number of mares exhibiting overt estrus (teasing score > 2) did not differ between treatment groups during the first and second postpartum ovulatory cycles. The intervals from foaling to first cycle ovulation, foaling to second cycle ovulation, and first to second cycle ovulation were also similar between treatment groups. All mares in both treatment groups conceived and maintained pregnancy. The first cycle conception rate and the number of cycles per conception did not differ between treatment groups. A high degree of body fat produced by overfeeding during gestation did not adversely affect postpartum reproductive performance in the multiparous mare.

Metabolic processes in isolated rat small intestine villus cells: effects of cis-diamminedichloroplatinum (II).

Intestinal cells were isolated from male Fischer 344 rats by the collagenase portal vein perfusion procedure and evaluated for direct effects of cis-diamminedichloroplatinum (CDDP) and ethylacrylate (EtAc) on metabolic activities. Specific activities of marker enzymes of intestinal crypt and villus cells indicated that the preparations contained predominantly villus cells. Cell viability was generally greater than 90%, and was maintained longest when the cells were suspended in M-199 medium supplemented with 1% BSA. EtAc, an industrial intermediate which is toxic to tissues which are directly exposed to this chemical, had no apparent effect on rates of glucose metabolism or protein synthesis in suspensions of the isolated intestinal cells. These metabolic processes, however, were inhibited by the anticancer agent, CDDP; the mechanism of cytotoxicity of CDDP may therefore be due to interference with intermediary metabolism. The present studies indicate that isolated intestinal cell suspensions may be useful in examining direct and immediate effects of chemicals which are toxic to the intestinal epithelium, and in evaluating potential cytotoxic effects of CDDP analogs which have been developed.

Effects of monensin on voluntary intake, eating and ruminating behavior and ruminal motility in heifers fed corn silage.

Eating and ruminating behavior and associated ruminal motility of six heifers (1/4 Brahman X 1/4 Jersey X 1/2 Angus, 290 kg average weight) given ad libitum access to corn silage with or without 100 mg monensin X head-1 X d-1 were examined according to a two-period crossover design. There was no effect (P greater than .05) of monensin on level of intake, daily and unitary eating, ruminating and masticating times [min X g dry matter-1 X (kg body weight X 75)-1], duration or number of these activity periods, duration of main meals or latency time for onset of rumination following cessation of main eating activities. With the monensin treatment, daily numbers of normal boli and total boli were decreased (P less than .05) and mean duration of one rumination bolus cycle was longer (P less than .05). Analysis of covariance indicated relationships between intake of corn silage and duration of the main morning meal, duration or number of rumination boli and total ruminal contractions were affected (P less than .01) by monensin. Frequency and unitary number of strong cranio-dorsal ruminal contractions were similar for both treatments. During eating, number of contractions per minute was about twice (2.55/min) that during idling and rumination activity (1.43/min and 1.22/min, respectively). The unitary daily number of contractions was negatively (P less than .05) related to level of intake. Total daily ruminal contractions were slightly reduced (-3.96%, P greater than .05) by monensin. Results are interpreted to suggest that monensin indirectly affects rumination through a lowered motility and thereby affects turnover, gut fill and intake.

Hepatic peroxisome proliferation and hypolipidemic effects of di(2-ethylhexyl)phthalate in neonatal and adult rats.

To determine the relative sensitivity of suckling rats as compared to adults to the effects of di(2-ethylhexyl) phthalate (DEHP), five daily oral doses of 0, 10, 100, 1000, or 2000 mg DEHP/kg body weight were given to male Sprague-Dawley rats beginning at 6, 14, 16, 21, 42, and 86 days of age. Twenty-four hours after the last dose, rats were sacrificed and plasma cholesterol and triglyceride levels and the activities of the hepatic peroxisomal enzymes, palmitoyl CoA oxidase and carnitine acetyltransferase, were determined. Suckling rats (1-3 weeks of age) suffered severe growth retardation at doses of 1000 mg/kg and death at 2000 mg/kg while older rats only showed decreased weight gain at 2000 mg/kg. Of particular interest was the lethality at doses of 1000 mg/kg at 14 days of age but not at 16 days or at other ages. Increases in relative liver weight and hepatic peroxisomal enzyme activities were similar in all age groups except the 14-day old group in which the increases were greater. Relative kidney weight was increased in 21-, 42-, and 86-day-old rats at the highest doses but not in younger rats. Hypolipidemia was observed only in 21-, 42-, and 86-day-old rats at doses of 1000 and 2000 mg/kg, while elevated plasma cholesterol levels were observed in 6- and 14-day-old rats at the 1000 mg/kg dose, possibly due to the dietary differences between suckling and weaned rats. The results suggest that neonatal and suckling rats are more sensitive to the lethal and growth retardation effects of DEHP than are adult rats, but the hepatic peroxisome proliferation is similar at all ages with the exception of a greater increase at 14 days of age.

Disposition of anesthetic and anesthetic-related agents in ruminants.

Many factors may influence the actions and fates of anesthetic and anesthetic-related agents in ruminant animals. These considerations need to be taken into account when these drugs are employed clinically. Some of the major principles governing the disposition of CNS-active drugs are reviewed, with special emphasis on the uniqueness of ruminant animals. General pharmacokinetic considerations are also covered as a preamble to a commentary on the kinetic characteristics of anesthetic and anesthetic-related agents that are commonly used in domesticated ruminants.

Concurrent use of corticosteroids and antimicrobial drugs in the treatment of infectious diseases in large animals.

A selection of the potential risks and benefits to be gained from the concurrent use of anti-inflammatory corticosteroids and antimicrobial agents in the treatment of infectious disease processes in large animals is reviewed. Although this form of combination therapy appears to be rational, there is cause for serious concern. Precautions and guidelines are presented for the therapeutic management of those cases in which the use of corticosteroids in conjunction with antibacterial agents is unavoidable.

Effects of dietary sodium bicarbonate and calcium chloride on physiological responses of lactating dairy cows in hot weather.

Twenty-four lactating cows were assigned randomly to three treatments to evaluate responses to large differences of dietary sodium and chloride. Treatments were corn-cottonseed meal-corn silage based complete rations with either: 1) .23% sodium chloride (control), 2) control plus 2.28% calcium chloride, or 3) control plus 1.70% sodium bicarbonate. Treatment effects were significant for urine pH (7.96, 5.41, 8.18), blood pH (7.50, 7.39, 7.49), partial pressure of oxygen (91.2, 99.4, 86.3 mm Hg), partial pressure of carbon dioxide (34.60, 30.57, 32.98 mm Hg), bicarbonate (26.20, 18.06, 24.64 meq/liter), total carbon dioxide (27.51, 19.18, 25.88 mM/liter), base excess (4.50, -4.31, 3.13 meq/liter), plasma chloride (93.4, 102.8, 95.7 meq/liter), serum potassium (3.26, 4.24, 4.14 meq/liter), and inorganic phosphorus (7.11, 5.61, 6.80 mg/100 ml). Blood glucose (45.1, 43.0, 55.5 mg/dl) and blood urea nitrogen (11.8, 8.7, 11.9 mg/dl) exhibited treatment effects. Respiration rates, 84.8, 61.8, 89.9 per min, and body temperatures, 39.7, 39.0, and 40.0 degrees C were significantly different. Lower intake of the high chloride diet and higher intake of the bicarbonate diet were probably responsible for some of the effects. Dietary electrolytes should receive attention in formulation because acid-base status of the animal is determined, in part, by ionic concentration and balance of the diet.