ABSTRACT
OBJECTIVES: To report a case series of thoracic bite trauma in dogs and cats and to evaluate risk factors for mortality. METHODS: A retrospective study concerning thoracic bite wounds in dogs and cats was performed. Lesions were categorized by depth of penetration: no wound, superficial, deep or penetrating. Thoracic radiographic reports were reviewed. Lesion management was classified as non-surgical, wound exploration, or explorative thoracotomy. RESULTS: Sixty-five cases were collected. Twenty-two percent of patients with normal respiratory patterns showed thoracic radiographic lesions. Respiratory distress was not correlated with mortality. Twenty-eight patients were presented with superficial wounds and 13 with deep wounds. Eight patients exhibited penetrating wounds. Radiographic lesions were observed in 77% of dogs and 100% of cats. Explorative thoracotomy was performed in 28% of patients, and surgical wound exploration in 17.2%. With the exception of skin wounds, thoracic wall discontinuity was the most frequent lesion. Thoracotomy was associated with increased length of hospitalisation but was not correlated with mortality. The mortality rate was 15.4%. No studied factor correlated with mortality, and the long-term outcomes were excellent. CLINICAL SIGNIFICANCE: A penetrating injury, more than three radiographic lesions, or both together seemed to be indicative of the need for a thoracotomy. In the absence of these criteria, systematic bite wound explorative surgery is recommended, with extension to thoracotomy if thoracic body wall disruption is observed.
Subject(s)
Bites and Stings/veterinary , Cat Diseases/pathology , Cats/injuries , Dog Diseases/pathology , Dogs/injuries , Thoracic Injuries/veterinary , Animals , Bites and Stings/mortality , Bites and Stings/pathology , Cat Diseases/mortality , Dog Diseases/mortality , Retrospective Studies , Risk Factors , Thoracic Injuries/mortalitySubject(s)
Scoliosis/diagnostic imaging , Scoliosis/pathology , Spine/growth & development , Spine/pathology , Tomography, X-Ray Computed , Animals , Disease Models, Animal , Lumbar Vertebrae/diagnostic imaging , Lumbar Vertebrae/growth & development , Lumbar Vertebrae/pathology , Spine/diagnostic imaging , Sus scrofa , Thoracic Vertebrae/diagnostic imaging , Thoracic Vertebrae/growth & development , Thoracic Vertebrae/pathologyABSTRACT
OBJECTIVE: To evaluate the validity of the common tangent and conventional tibial plateau angle methods for measuring the patellar tendon angle (PTA) in dogs. METHODS: Radiographs of cadaveric stifles (n = 20) placed at 135° in true lateral position were obtained to measure the PTA with both methods. A Kirschner wire was inserted perpendicularly to the patellar tendon at its insertion on the tibia and the stifle was dissected. Two Kirschner wires were then used to identify the anatomical landmarks of the tibial plateau. A digital image was obtained of the proximal tibia in true lateral position. Six blinded observers measured each PTA digitally while the anatomical PTA was determined by an independent blinded observer from the angle between the line representing the tibial plateau and the Kirschner wire representing the perpendicular to the patellar tendon. The agreement between the methods was determined statistically from an intraclass correlation coefficient (ICC). RESULTS: The global ICC for the common tangent method (0.44) and for the conventional method (0.4) indicated that their overall validity is poor. The measurements obtained by common tangentmethod and conventional method were respectively below and above the anatomical measurements. The reproducibility of the PTA measurements based on images of the dissected stifles was very good. CLINICAL SIGNIFICANCE: Both the common tangent and conventional methods show poor concordance with the anatomical measurement of PTA. Further studies are needed to determine if errors in measurements affect the clinical outcome.
Subject(s)
Dogs , Patellar Ligament/diagnostic imaging , Stifle/anatomy & histology , Animals , Cadaver , Radiography , Stifle/diagnostic imaging , Tibia/diagnostic imagingABSTRACT
OBJECTIVE: To determine association between computed tomography measurements of spinal cord compression and postoperative outcome. METHODS: A retrospective review of medical records of dogs presenting with intervertebral disease. Data were collected with a minimum of 2 years follow-up period. Computed tomography morphometric indices, particularly the ratio of spinal cord or herniated disc to vertebral canal dimensions, were obtained from survey and myelogram computed tomographic images. The pattern of disc disease was scored as single or continuous (multiple herniated discs), and was compared to postoperative outcome. RESULTS: Fifty-two dogs were included. There was no significant correlation between the degree of spinal cord compression and postoperative outcome. However, postoperative outcome differed significantly between dogs with single or continuous patterns of disc disease (P=0·001). Of those with single patterns, 75% had a postoperative outcome score greater than 75% while 75% of continuous pattern cases had scores lower than 83%. CLINICAL SIGNIFICANCE: Simple observation of the pattern of disc disease as revealed by computed tomography could be used as a prognostic indicator. The outcome tends to be better for single patterns of disc disease, whereas the outcome was poor for most cases with continuous patterns.
Subject(s)
Dog Diseases/diagnostic imaging , Intervertebral Disc Displacement/veterinary , Myelography/veterinary , Animals , Dog Diseases/diagnosis , Dog Diseases/surgery , Dogs , Female , Intervertebral Disc Displacement/diagnosis , Intervertebral Disc Displacement/diagnostic imaging , Intervertebral Disc Displacement/surgery , Lumbar Vertebrae/diagnostic imaging , Male , Thoracic Vertebrae/diagnostic imaging , Tomography, X-Ray Computed , Treatment OutcomeSubject(s)
Bandages , Carpus, Animal/physiology , Range of Motion, Articular , Walking , Animals , DogsABSTRACT
OBJECTIVE: To report the successful use of recombinant human bone morphogenetic protein-2 (rhBMP-2) in the treatment of an antebrachial non-union, secondary to gunshot fracture, stabilized with circular external fixation in a cat. PROCEDURE: Following a diagnosis of a highly comminuted gunshot fracture of the distal right radius and ulna, the fracture was stabilized with a circular external fixation. A two-ring frame was placed in closed fashion. RESULTS: The skin wound healed uneventfully by second intention in 21 days. Twenty-eight weeks after external fixation, bone healing was absent. 0.8mL of 0.2mg/mL of rhBMP-2 in two collagen sponges was placed in the bone defect. Eight weeks after rhBMP-2 implantation, an early bone healing response was noted on radiographic evaluation. Sixteen weeks after rhBMP-2 implantation, fracture union was achieved. DISCUSSION: To the authors' knowledge, 160 µg is the lowest reported dose of rhBMP-2 that leads to bony union in a cat. However as an individual case study, this report can not be used as evidence that rhBMP-2 at this lower dose is appropriate for use in all cats. Further studies are needed to establish the minimum efficient dose of rhBMP-2 in cats.
Subject(s)
Bone Morphogenetic Protein 2/therapeutic use , Cats/injuries , External Fixators/veterinary , Forelimb/pathology , Fractures, Ununited/veterinary , Wounds, Gunshot/veterinary , Animals , Cats/surgery , Fractures, Ununited/drug therapy , Fractures, Ununited/surgery , Male , Wounds, Gunshot/surgeryABSTRACT
The objective of this study was to investigate the type of chemical restraint used by French practitioners to perform official hip screening radiographs, to determine the proportion of dogs under general anesthesia versus dogs under sedation, and to search for a difference in hip dysplasia (HD) prevalence between the two groups. From September 2005 to August 2008, 3302 conventional ventrodorsal hip extended radiographs sent for official scoring to the same panellist were selected because information related to the type of chemical restraint had been provided. There were 2825 dogs under general anesthesia and 477 were sedated. Chemical restraint used by French veterinarians to perform HD screening radiographs is mainly based on general intra-venous anesthesia with an alpha2 agonist associated with ketamine. A single injection of alpha2 agonist is also mostly used for dogs which are radiographed while under sedation. A very low (1.7%) difference in HD prevalence was noted between the anesthetized and the sedated group. Except for acepromazine, which has been demonstrated to provide insufficient muscle relaxation to show evidence of hip laxity, the protocols seem acceptable as regards the Federation Cynologique Internationale requirements for HD screening.
Subject(s)
Hip Dysplasia, Canine/diagnostic imaging , Radiography/veterinary , Restraint, Physical/veterinary , Acepromazine/administration & dosage , Anesthesia, General/veterinary , Anesthetics, General/administration & dosage , Animals , Dogs , France , Hypnotics and Sedatives/administration & dosage , Medetomidine/administration & dosage , Radiography/methods , Restraint, Physical/methods , Retrospective Studies , Xylazine/administration & dosageABSTRACT
In order to look for phenotypic correlation between hip (HD) and elbow (ED) dysplasia, we used radiographic scoring obtained from 1,411 dogs of different breeds, which were evaluated for authoritative grading of both conditions. In this population, we found that the risk ratio for an animal to be simultaneously affected by HD and ED is 1.67. For a dog with ED, the risk ratio to be affected by HD increases as the ED grade increases. Similarly, for a dog affected by HD, the risk ratio to be affected by ED increases as the HD grade increases. In a dog affected by HD or ED, the clinician should look for the second condition in the same animal. Due to the low, yet positive correlation, selection against one trait will not affect the other trait sufficiently. Therefore selection has to be conducted at reduction of HD as well as reduction of ED.
Subject(s)
Dog Diseases/epidemiology , Forelimb , Hip Dysplasia, Canine/epidemiology , Joint Diseases/veterinary , Animals , Dog Diseases/diagnostic imaging , Dogs , Female , Hip Dysplasia, Canine/diagnostic imaging , Joint Diseases/diagnostic imaging , Joint Diseases/epidemiology , Male , Odds Ratio , Radiography , Species SpecificityABSTRACT
In order to determine the prevalence of hip dysplasia (HD) from radiographs that were submitted for authorative grading, and its changes over the time in 31 breeds of dogs in France, a 14 year-retrospective study was conducted. Significant differences were observed between breeds, with HD prevalence ranging from 59.7% (Cane Corso) to 3.9% (Siberian Husky). When comparing the 1993-1999 with the 2000-2006 period in 15 breeds, a significant decrease in HD prevalence was detected in Berger Picard, Bernese Mountain dog, Briard, Gordon Setter, White Swiss Sheepdog and Rottweiler. Modifications observed in the other breeds were not statistically significant.
Subject(s)
Breeding , Hip Dysplasia, Canine/diagnostic imaging , Hip Dysplasia, Canine/epidemiology , Hip Joint/diagnostic imaging , Animals , Dogs , Female , France/epidemiology , Hip Dysplasia, Canine/genetics , Male , Prevalence , Radiography , Retrospective StudiesABSTRACT
OBJECTIVES: To develop a protocol for rabbit knee joint ultrasonography (US); to grade ultrasonographically the meniscal injuries of the anterior cruciate ligament transection (ACLT) rabbit model of osteoarthritis (OA); to assess with US the effectiveness of the ACLT; to compare final US with macroscopy for the evaluation of medial and lateral meniscal injuries depending on the age and weight when ACLT is performed. METHODS: Twenty-two skeletally mature and adolescent New Zealand white rabbits were housed during the same period at the Institut Claude-Bourgelat, Lyon, France. Surgical ACLT was performed in the left knee of nine adolescent and five adult rabbits. Final US and macroscopic semi-quantitative grading of the meniscal injuries were compared 5 months after ACLT. RESULTS: A standardised protocol was developed to evaluate the rabbit knee joint. US was performed in both control and ACLT knees. Normal and abnormal meniscal US appearances were described. A semi-quantitative scale to grade US meniscal injuries was created. Macroscopic and US total meniscal scores were significantly positively correlated (P<0.001, r=0.70). US detection of meniscal injuries was 92% sensitive and 87.5% specific compared to macroscopy. Positive and negative predictive values of US were, respectively, 92% and 87.5%. US detection of the ACLT effectiveness was 100% specific and 78.5% sensitive. CONCLUSION: A significant relationship was found between ultrasonographic and macroscopic grading of meniscal injuries. US was both specific and sensitive in detecting meniscal lesions. We propose US as a non-invasive, non-expensive, in vivo imaging technique for preclinical studies in the ACLT rabbit OA model.
Subject(s)
Menisci, Tibial/diagnostic imaging , Osteoarthritis, Knee/diagnostic imaging , Severity of Illness Index , Animals , Anterior Cruciate Ligament/surgery , Arthritis, Experimental , Menisci, Tibial/pathology , Osteoarthritis, Knee/pathology , Rabbits , Range of Motion, Articular , Sensitivity and Specificity , Stifle/diagnostic imaging , Stifle/surgery , UltrasonographyABSTRACT
The prevalence of rotation of the pelvis along its length axis was noted, as was the number of rotations towards the right or left hand side of the dog, on 7,012 conventional hip extended radiographs, which were sent for official screening. 29.8% of the radiographs showed a rotation the pelvis. The rotation was statistically more frequent towards the left hand side of the dog. The number of rejected radiographs for too important pelvis rotation was only 5.2%. The consequences of the pelvis rotation on the Norberg-Olsson angle, on the dorsal femoral head coverage, and in the aspect of cranial acetabular edge have to be taken into account when scoring the dog for hip dysplasia.
Subject(s)
Hip Dysplasia, Canine/diagnostic imaging , Radiography/veterinary , Rotation , Animals , Dogs , France/epidemiology , Observer Variation , Predictive Value of Tests , Prevalence , Radiography/methods , Radiography/statistics & numerical data , Severity of Illness IndexABSTRACT
Hip dysplasia (HD) scores, based on the five grades, as defined by the Fédération Cynologique Internationale, were compared between anaesthetized (group 1, n = 3839) and non-sedated non-anaesthetized dogs (group 2, n = 1517). Each dog was radiographed in the standard ventro-dorsal hip joint extended position. Each radiograph was evaluated by the same reader blinded regarding the dog's status of anaesthesia. Results showed that there was a significant difference in hip dysplasia prevalence between group 1 (22%) compared with group 2 (9%) (P < 0.005). This difference was the result of a lower rate of hip-joint laxity assessment and the measurement of Norberg-Olsson angle <105 degrees in group 2 compared with group 1. The acetabular and femoral morphologies were not significantly different between the groups. The data confirm that the scoring of dogs for HD on standard radiographs with the hip joints extended is influenced by anaesthesia.
Subject(s)
Anesthesia/veterinary , Hip Dysplasia, Canine/pathology , Pain/veterinary , Animals , Dogs , Female , Hip Dysplasia, Canine/classification , Hip Dysplasia, Canine/diagnostic imaging , Male , Pain Measurement , Radiography , Severity of Illness IndexABSTRACT
Five hundred and twenty German shepherd dogs were screened for elbow dysplasia. The following primary lesions were analysed: joint incongruity (JI), fragmented medial coronoid process (FCP), osteochondrosis or osteochondritis of the medial humeral condyle and ununited anconeal process (UAP). Three radiographic views were used for each joint to achieve a definitive diagnosis. The prevalence of elbow dysplasia was 19.4 per cent. The most frequent lesion was JI (16.3 per cent), followed by FCP (11.3 per cent). UAP was diagnosed rarely (1.1 per cent). Combinations of lesions were very frequent (42.2 per cent of the dysplastic elbows). Although these results may be biased due to prescreening of dogs with UAP, it should be highlighted that JI and FCP occur frequently in German shepherd dogs and are probably the most common primary lesions of elbow dysplasia, although they have been under-reported until now.
Subject(s)
Dog Diseases/epidemiology , Forelimb , Joint Diseases/veterinary , Animals , Dog Diseases/diagnostic imaging , Dog Diseases/etiology , Dogs , Female , France/epidemiology , Joint Diseases/epidemiology , Male , Pedigree , Prevalence , RadiographyABSTRACT
Atractyloside (Atr) binds to the adenine nucleotide translocator (ANT) and inhibits ANT-mediated ATP/ADP exchange on the inner mitochondrial membrane. In addition, Atr can trigger opening of a non-specific ion channel, within the ANT-containing permeability transition pore complex (PTPC), which is subject to redox regulation and inhibited by cyclosporin A (CsA). Here we show that the cytotoxic effects of Atr, both in vivo and in vitro, are determined by its capacity to induce PTPC opening and consequent mitochondrial membrane permeabilization (MMP). Thus, the Atr-induced MMP and death of cultured liver cells are both inhibited by CsA as well as by glutathione (GSH) and enhanced by GSH depletion. Similarly, the hepatorenal toxicity of Atr, assessed in vivo, was reduced by treating mice with CsA or a diet rich in sulfur amino acids, a regime which enhances mitochondrial GSH levels. Atr injection induced MMP in hepatocytes and proximal renal tubular cells, and MMP was reduced by either CsA or GSH. Acetaminophen (paracetamol)-induced acute poisoning was also attenuated by CsA and GSH, both in vitro and in vivo. Altogether these data indicate that PTPC-mediated MMP may determine the hepatorenal toxicity of xenobiotics in vivo.
Subject(s)
Atractyloside/toxicity , Enzyme Inhibitors/toxicity , Hepatocytes/drug effects , Intracellular Membranes/drug effects , Kidney/drug effects , Liver/drug effects , Mitochondria/drug effects , Animals , Apoptosis/drug effects , Apoptosis/physiology , Atractyloside/antagonists & inhibitors , Cell Membrane Permeability/drug effects , Cell Membrane Permeability/physiology , Cells, Cultured , Cyclosporine/pharmacology , Fluorescent Antibody Technique , Glutathione/metabolism , Glutathione/pharmacology , Hepatocytes/metabolism , Hepatocytes/ultrastructure , Humans , Intracellular Membranes/metabolism , Intracellular Membranes/ultrastructure , Ion Channels/drug effects , Ion Channels/metabolism , Kidney/metabolism , Kidney/ultrastructure , Liver/metabolism , Liver/ultrastructure , Male , Mice , Mice, Inbred ICR , Microscopy, Electron , Mitochondria/metabolism , Mitochondria/ultrastructureABSTRACT
Whereas alpidem is hepatotoxic, zolpidem is not. Despite closely related chemical structures, alpidem, but not zolpidem, is a peripheral benzodiazepine receptor (PBR) ligand, and is also more lipophilic than zolpidem. We compared their effects in isolated rat liver mitochondria and rat hepatocytes. Zolpidem did not affect calcium-induced mitochondrial permeability transition (MPT) in mitochondria, caused little glutathione depletion in hepatocytes, and was not toxic, even at 500 microM. At 250 to 500 microM, alpidem prevented calcium-induced MPT in isolated mitochondria, but caused severe glutathione depletion in hepatocytes that was increased by 3-methylcholanthrene, a cytochrome P4501A inducer, and decreased by cystine, a glutathione precursor. Although cell calcium increased, mitochondrial cytochrome c did not translocate to the cytosol and cells died of necrosis. Cell death was prevented by cystine, but not cyclosporin A, an MPT inhibitor. At low concentrations (25-50 microM), in contrast, alpidem accelerated calcium-induced MPT in mitochondria. It did not deplete glutathione in hepatocytes, but nevertheless caused some cell death that was prevented by cyclosporin A, but not by cystine. Alpidem (10 microM) also increased the toxicity of tumor necrosis factor-alpha (1 ng/ml) in hepatocytes. In conclusion, low concentrations of alpidem increase both calcium-induced MPT in mitochondria, and TNF-alpha toxicity in cells, like other PBR ligands. Like other lipophilic protonatable amines, however, alpidem inhibits calcium-induced MPT at high concentrations. At these high concentrations, toxicity involves cytochrome P4501A-mediated metabolic activation, glutathione depletion, and increased cell calcium, without MPT involvement. In contrast, zolpidem has no mitochondrial effects, causes little glutathione depletion, and is not toxic.
Subject(s)
Anti-Anxiety Agents/toxicity , Hepatocytes/drug effects , Imidazoles/toxicity , Mitochondria, Liver/drug effects , Pyridines/toxicity , Receptors, GABA-A/drug effects , Adenosine Diphosphate/pharmacology , Animals , Anti-Anxiety Agents/pharmacokinetics , Biotransformation/drug effects , Cells, Cultured , Cytochrome c Group/metabolism , GABA-A Receptor Agonists , Hepatocytes/metabolism , Imidazoles/pharmacokinetics , Male , Membrane Potentials/physiology , Mitochondria, Liver/metabolism , Oxidation-Reduction , Oxygen Consumption/physiology , Permeability , Pyridines/pharmacokinetics , Rats , Rats, Sprague-Dawley , ZolpidemABSTRACT
Glutathione depletion either decreased or increased death-receptor-mediated apoptosis in previous studies. Comparison of the durations of glutathione depletion before death-receptor stimulation in these studies might suggest a different effect of prolonged versus acute thiol depletion. We compared the effects of the prolonged glutathione depletion caused by a sulfur amino acid-deficient (SAA(-)) diet and the acute depletion caused by a single dose of phorone on hepatic apoptosis triggered by the administration of an agonistic anti-Fas antibody. The chronic SAA(-) diet did not affect hepatic Fas or Bcl-XL, but increased p53 and Bax, and exacerbated Fas-mediated mitochondrial membrane depolarization, electron-microscopy-proven outer mitochondrial membrane rupture, cytochrome c translocation to the cytosol, and caspase 3 activation. These effects were prevented by cyclosporin A, an inhibitor of mitochondrial permeability transition. The SAA(-) diet increased internucleosomal DNA fragmentation, the percentage of apoptotic hepatocytes, serum alanine transaminase (ALT) activity, and mortality after Fas stimulation. Despite a similar decrease in hepatic glutathione, administration of a single dose of phorone 1 hour before the anti-Fas antibody did not change p53 or Bax, and did not enhance Fas-induced mitochondrial permeability transition and toxicity. However, 4 repeated doses of phorone (causing more prolonged glutathione depletion) increased Bax and Fas-mediated toxicity. In conclusion, a chronic SAA(-) diet, but not acute phorone administration, increases p53 and Bax, and enhances Fas-induced mitochondrial permeability transition and apoptosis. Thiol depletion could cause oxidative stress that requires several hours to increase p53; the latter induces Bax, which translocates to mitochondria after Fas stimulation.
Subject(s)
Apoptosis/physiology , Glutathione/deficiency , Mitochondria, Liver/metabolism , Proto-Oncogene Proteins c-bcl-2 , fas Receptor/physiology , Amino Acids/administration & dosage , Animals , Caspase 3 , Caspases/metabolism , Cyclosporine/pharmacology , Cytochrome c Group/metabolism , Diet , Glutathione/antagonists & inhibitors , Hepatocytes/drug effects , Hepatocytes/ultrastructure , Ketones/pharmacology , Liver/metabolism , Male , Mice , Mitochondria, Liver/physiology , Permeability , Protective Agents/pharmacology , Proto-Oncogene Proteins/metabolism , Sulfur/administration & dosage , Time Factors , Tumor Suppressor Protein p53/metabolism , bcl-2-Associated X Protein , fas Receptor/pharmacologyABSTRACT
This report describes two animals (one dog and one cat) with a retained surgical sponge. Both had nonspecific clinical signs. Clinical examination, ultrasonography and cytologic examination were used to identify an abdominal mass compatible with a granuloma. The lesions were surgically removed and confirmed histologically as granulomas secondary to a retained sponge. The ultrasonographic appearance was very similar in both animals.
Subject(s)
Cat Diseases/diagnostic imaging , Dog Diseases/diagnostic imaging , Granuloma, Foreign-Body/veterinary , Abdomen , Animals , Cats , Diagnosis, Differential , Dogs , Female , Granuloma, Foreign-Body/diagnostic imaging , Surgical Sponges , UltrasonographyABSTRACT
PURPOSE OF THE STUDY: Progressive limb lengthening with an external fixator often leads to pin-related complications. A new technique allowing progressive lengthening with a centromedullary nail without external fixation has been developed. This original double-locked device consists of matching male and female components fitted with a continuous thread. Lengthening is achieved via a one-way ratchet system. Twelve back-and-forth movements produce 1.25 mm lengthening. MATERIAL AND METHODS: We tested this new device on 20 sheep and compared results with external fixation lengthening in 20 other sheep. The animals were divided into groups for sacrifice on days 5, 10, 20, 45 and 90. Serial x-ray were obtained for all animals. In the 45-day and 90-day groups, histomorphometric (trichrome goldner coloration and polarized light microscopy) and densitometric studies were also performed. Bone mineral density (BMD) was determined and bone trabecular density (BTD) and trabecular bone volume (TBV) were expressed in percent of bone trabecular surface area. RESULTS: Mean lengthening in the 45-day and 90-day groups was 39 mm for the nail and 20 mm for external fixation (1 mm/day). At 90 days, 3 sheep out of 4 had consolidated radiologically with external fixation and 2 out of 4 with the nail. BMD was slightly better for external fixation (0.811 vs 0.695/cm(2)). This difference could probably be attributed to the greater lengthening obtained with the nail. At 45 days, BMD was the same (0.6 g/cm(2)) for both devices. BTD was nearly two-fold higher for the nail compared with external fixation (59.65% vs 32.61% at 90 days), most probably due to primary bone formation. The histomorphometric study allowed an analysis of the osteoid border. Bone quality obtained in the bone regenerate with the nail was superior to that obtained with external fixation. Primary bone formation resulted from membrane ossification with direct transformation of fibroblasts into osteoblasts. CONCLUSION: This work demonstrated that progressive lengthening can be achieved with a specifically designed centromedullary nail without iterative opening of the operative site. Tolerance to this type of device and quality of the bone regenerate are altogether satisfactory.
Subject(s)
Bone Lengthening/instrumentation , Bone Nails/standards , External Fixators/standards , Femur/surgery , Absorptiometry, Photon , Animals , Biopsy , Bone Density , Bone Lengthening/adverse effects , Bone Lengthening/methods , Bone Nails/adverse effects , Bone Regeneration/physiology , Equipment Design , External Fixators/adverse effects , Female , Femur/diagnostic imaging , Femur/ultrastructure , Fibroblasts/physiology , Materials Testing , Osteoblasts/physiology , Sheep , Time FactorsABSTRACT
BACKGROUND/AIMS: Although sublingual buprenorphine is safely used as a substitution drug in heroin addicts, large overdoses or intravenous misuse may cause hepatitis. Buprenorphine is N-dealkylated to norbuprenorphine by CYP3A. METHODS: We investigated the mitochondrial effects and metabolic activation of buprenorphine in isolated rat liver mitochondria and microsomes, and its toxicity in isolated rat hepatocytes and treated mice. RESULTS: Whereas norbuprenorphine had few mitochondrial effects, buprenorphine (25-200 microM) concentrated in mitochondria, collapsed the membrane potential, inhibited beta-oxidation, and both uncoupled and inhibited respiration in rat liver mitochondria. Both buprenorphine and norbuprenorphine (200 microM) underwent CYP3A-mediated covalent binding to rat liver microsomal proteins and both caused moderate glutathione depletion and increased cell calcium in isolated rat hepatocytes, but only buprenorphine also depleted cell adenosine triphosphate (ATP) and caused necrotic cell death. Four hours after buprenorphine administration to mice (100 nmol/g body weight), hepatic glutathione was unchanged, while ATP was decreased and serum transaminase increased. This transaminase increase was attenuated by a CYP3A inducer and aggravated by a CYP3A inhibitor. CONCLUSIONS: Both buprenorphine and norbuprenorphine undergo metabolic activation, but only buprenorphine impairs mitochondrial respiration and ATP formation. The hepatotoxicity of high concentrations or doses of buprenorphine is mainly related to its mitochondrial effects.
Subject(s)
Aryl Hydrocarbon Hydroxylases , Buprenorphine/pharmacokinetics , Buprenorphine/toxicity , Liver/drug effects , Liver/metabolism , Narcotics/pharmacokinetics , Narcotics/toxicity , Adenosine Triphosphate/biosynthesis , Alkylation , Animals , Biotransformation , Buprenorphine/analogs & derivatives , Cytochrome P-450 CYP3A , Cytochrome P-450 Enzyme System/metabolism , In Vitro Techniques , Male , Membrane Potentials/drug effects , Mice , Mice, Inbred ICR , Microsomes, Liver/drug effects , Microsomes, Liver/metabolism , Mitochondria, Liver/drug effects , Mitochondria, Liver/metabolism , Oxidation-Reduction , Oxidoreductases, N-Demethylating/metabolism , Permeability , Protein Binding , Rats , Rats, Sprague-Dawley , Uncoupling Agents/pharmacologyABSTRACT
A 30-yr-old untamed European female brown bear (Ursus arctos arctos) with a craniodorsal luxation of the right femoral head and bilateral degenerative joint disease of the coxofemoral joint had a femoral head and neck excision following unsatisfactory conservative medical therapy. The bear was injected with zolazepam-tiletamine, and anesthesia was induced with i.v. thiopental and maintained with isoflurane in oxygen via endotracheal tube. A lumbosacral epidural injection of medetomidine-bupivacaine provided additional analgesia. Slight initial cardiorespiratory depression was counteracted with fluid and inotropic drug administration and ventilatory assistance. The bear's gluteal muscle anatomy differs from that of the dog. Recovery was uneventful. The bear was confined indoors for 6 wk and was able to ambulate normally within 6 mo.