In vivo BMP-7 (OP-1) enhancement of osteoporotic vertebral bodies in an ovine model.

BACKGROUND CONTEXT: Prevention of osteoporotic vertebral fractures could help at-risk individuals avoid the pain and morbidity associated with these fractures. Currently, patients with osteoporosis are treated with systemic medications to reduce fracture risk. Although effective, these therapies do not eliminate fractures and also tend to have a gradual time-dependent effect on fracture risk. The mechanism of action of the bone morphogenetic protein (BMP) family theoretically makes these molecules candidates for rapidly enhancing local bone structure. STUDY DESIGN: An in vivo study analyzing the effects of BMP-7 (osteogenic protein 1 [OP-1]) treatment on osteopenic ovine vertebral architecture and biomechanics. PURPOSE: We tested the hypothesis that local injection of OP-1 into osteopenic ovine vertebrae will improve bone mass and trabecular distribution, thereby reducing bone fragility and fracture risk. We specifically evaluated compressive biomechanics and morphology of osteopenic ovine vertebral bodies 6 months after local OP-1 treatment. STUDY DESIGN: In vivo animal study. METHODS: Skeletally mature sheep (n=24) underwent ovariectomy and were placed on low cation relative to anion diet. These interventions reduce bone density and induce skeletal fragility. After 6 months, sheep were randomly assigned to six treatment groups based on OP-1 dose (370 mg or 0 mg) and carrier with 4 animals/treatment group. Carriers A and B were poly-L-glycolic acid (PLGA) biospheres with different release kinetics (B allowing sustained BMP release); Carrier C was carboxymethylcellulose. After creating an 8-mm-diameter defect in the midvertebral body, sheep underwent intravertebral body implantation at two nonadjacent levels. Animals were euthanized 6 months after implantation and bone mineral density (BMD), biomechanics, and histomorphometry were assessed. Two-way analysis of variance was used to determine effects of OP-1 (alpha=0.05). RESULTS: An 81.9%, 333.2%, and 39.9% increase in stiffness was seen for OP-1 treated vertebra with Carriers A, B, and C respectively. Although these effects did not reach statistical significance, trends toward improvement were evident. Histology showed varied degrees of bony healing in the injection sites. Histomorphometrically, OP-1 treated vertebrae showed improvements in percent bone of up to 38% and star volume of up to 55% (with Carrier B). Improvements in whole vertebral body BMD were not detected for any treatment. CONCLUSION: In this study, local OP-1 treatment showed a positive trend in improving mechanical strength and histomorphometric parameters of osteopenic vertebra, despite the absence of consistent change in BMD. Controlled slow release of OP-1 using PLGA microspheres appeared to be the most effective method of protein delivery. In conclusion, we feel that the pilot data suggest that the use of OP-1 in the treatment of vertebral osteoporosis in an attempt to enhance bone strength merits further study.

Direct current electrical stimulation increases the fusion rate of spinal fusion cages.

STUDY DESIGN: A randomized experimental evaluation of direct current stimulation in a validated animal model with an experimental control group, using blinded radiographic, biomechanical, histologic, and statistical measures. OBJECTIVES: To evaluate the efficacy of the adjunctive use of direct current stimulation on the fusion rate and speed of healing of titanium interbody fusion cages packed with autograft in a sheep lumbar interbody fusion model. SUMMARY OF BACKGROUND DATA: Titanium lumbar interbody spinal fusion cages have been reported to be 90% effective for single-level lumbar interbody fusion. However, fusion rates are reported to be between 70% and 80% in patients with multilevel fusions or with risk factors such as obesity, tobacco use, or metabolic disorders. The authors hypothesized that direct current stimulation would increase the fusion rate of titanium interbody fusion cages packed with autograft in a sheep lumbar interbody fusion model. METHODS: Twenty-two sheep underwent lumbar discectomy and fusion at L4-L5 with an 11- x 20-mm Bagby and Kuslich (BAK) cage packed with autograft. Seven sheep received a BAK cage and no current. Seven sheep had a cage and a 40-microA current applied with a direct current stimulator. Eight sheep had a BAK cage and a 100-microA current applied. All sheep were killed 4 months after surgery. The efficacy of electrical stimulation in promoting interbody fusion was assessed by performing radiographic, biomechanical, and histologic analyses in a blinded fashion. RESULTS: The histologic fusion rate increased as the direct current dose increased from 0 microA to 40 microA to 100 microA (P < 0.009). Histologically, all animals in the 100-microA group had fusions in both the right and left sides of the cage. Direct current stimulation had a significant effect on increasing the stiffness of the treated motion segment in right lateral bending (P < 0.120), left lateral bending (P < 0.017), right axial rotation (P < 0.004), left axial rotation (P < 0.073), extension (P < 0.078), and flexion (P < 0.029) over nonstimulated levels. CONCLUSION: Direct current stimulation increased the histologic and biomechanical fusion rate and the speed of healing of lumbar interbody spinal fusion cages in an ovine model at 4 months.

Catheterization of the subarachnoid space in rabbits using a Vascular Access Port.

A surgical technique allowing chronic access to the subarachnoid space in unanesthetized rabbits was devised using the Vascular Access Port system. Instrumentation provides the investigator with a method of measuring intracranial pressure and sampling cerebrospinal fluid in awake rabbits. The catheter is introduced into the dorsal cervical subarachnoid space at the C4-C5 intervertebral space via dorsal laminectomy and passed cranially into the cisterna magna. The access port is subcutaneously implanted in the dorsal thoracic region between the scapulas. This system reduces the potential for infection, is not easily removed by the animal, and is relatively easy to access with minimal discomfort for the animal.

Histochemical study of the anulus fibrosus in normal canine caudal cervical intervertebral discs.

A qualitative assessment of glycosaminoglycans (GAGs) in the non-chondrodystrophoid canine cervical anulus fibrosus was performed using the Alcian blue/critical electrolyte concentration staining technique. Estimates of GAG concentration were deduced for two groups of dogs (average age four and eight years) by determining the hyaluronic acid, chondroitin sulphates and keratan sulphate 'alcianophilic indices'. Keratan sulphate was the predominant GAG in the four-year-old group of dogs. The concentration of keratan sulphate was equal to that of chondroitin sulphates in the eight-year-old group and the total GAG concentration was decreased. This qualitative assessment indicated that the concentrations of keratan sulphate decreased and chondroitin sulphates increased between four and eight years of age. Similar conclusions have not been reported for anuli in the thoracic and lumbar regions of the canine spine.

Use of adult dog serum as a substitute for colostrum in the neonatal dog.

Failure to obtain passive transfer of immunity via colostrum can be detrimental to the health and survival of a young pup. It has been stated that pups that do not receive colostrum in the first 2 days after birth, be given adult dog serum as a source of protective immunoglobulins. Twenty-five Beagle pups were obtained by cesarean section from 6 Beagle bitches. The pups were allotted to 3 groups at birth. Group 1 was a control group and was allowed to suckle colostrum. Group-2 pups received 22 ml of pooled adult dog serum/kg of body weight (10 ml/lb) SC at birth. Group-3 pups were given 22 ml of pooled adult dog serum/kg by stomach tube at birth. Pups from groups 2 and 3 were separated from the bitch for 48 hours to prevent colostral antibody absorption and were fed a commercially available milk replacer by stomach tube. After 48 hours, all pups were returned to the bitch until they were weaned at 6 weeks of age. Blood samples were collected from all of the pups at birth and on days 1, 2, 7, 14, 21, 28, and 35. The concentration of IgA, IgG, and IgM in serum was determined by radial immunodiffusion and compared by use of a one-way analysis of variance. The control pups had significantly higher serum concentrations of IgA and IgG, than the pups in groups 2 and 3 on days 1 and 2 and 2 and 7, respectively. Group-2 pups had significantly higher serum IgM concentrations on day 1 than either group 1- or group-3 pups.

Effect of metoclopramide on fed-state gastric myoelectric and motor activity in dogs.

OBJECTIVE: To investigate the effects of metoclopramide, a putative gastroprokinetic agent, on dogs that had recovered from gastric dilatation-volvulus (GDV), a disorder characterized by delayed gastric emptying. ANIMALS: 6 healthy dogs and 5 dogs after treatment and recovery from GDV. PROCEDURE: Baseline recordings of gastric electrical and contractile activities were made 8 or 10 days after circumcostal gastropexy and implantation of serosal electrodes and strain-gauge force transducers. Gastric activities were recorded again the next day after treatment with the clinically recommended oral metoclopramide dose (0.3 mg/kg of body weight) administered a half hour before feeding. Recordings were analyzed to determine gastric slow-wave frequency, presence of slow-wave dysrhythmia, slow-wave propagation velocity, coupling of contractions to slow waves, a motility index based on relative contractile amplitudes, and onset of contractions after a standardized meal. RESULTS: Significant differences in gastric electrical or contractile activities were not detected after metoclopramide treatment in dogs with GDV. Compared with control dogs after metoclopramide treatment, gastric slow-wave propagation velocity was significantly (P = 0.03) faster for the dogs with GDV at postprandial minute 90. CONCLUSION: At a clinically recommended dosage, metoclopramide treatment did not change gastric myoelectric and motor activities in a way that would promote increased gastric emptying in dogs with GDV. CLINICAL RELEVANCE: Metoclopramide treatment may not benefit dogs with GDV and delayed gastric emptying.

Gastric emptying of nondigestible radiopaque markers after circumcostal gastropexy in clinically normal dogs and dogs with gastric dilatation-volvulus.

Using radiopaque particles mixed with food, gastric emptying was assessed in healthy dogs not subjected to surgery, in healthy dogs 9 to 35 days after circumcostal gastropexy, and, in dogs 1 to 54 months after surgical treatment and recovery from gastric dilatation-volvulus (GDV). Circumcostal gastropexy surgery did not alter the 90% gastric emptying time for radiopaque particles in healthy dogs. However, 90% gastric emptying time was significantly (P less than 0.05) increased after circumcostal gastropexy in dogs with GDV, compared with healthy dogs after the same surgical procedure and recovery period. These results imply that dogs with GDV have delayed gastric emptying of solid particles. Whether delayed gastric emptying of markers detected in affected dogs after surgical treatment and recovery was the result or the cause of GDV was not determined. Results indicate that circumcostal gastropexy could be recommended as a prophylactic procedure for GDV in large breeds with deep thorax, because delayed gastric emptying of markers secondary to the surgical procedure is unlikely.

Gross and histologic evaluation of hepatogastric ligaments in clinically normal dogs and dogs with gastric dilatation-volvulus.

OBJECTIVE--To investigate any potential structural differences in hepatogastric ligaments between clinically normal dogs and dogs with gastric dilatation-volvulus (GDV). DESIGN--Case-control study. ANIMALS--Hepatogastric ligaments were examined in 13 large-breed control dogs and in 13 large-breed dogs referred for surgical treatment of GDV. PROCEDURE--Measurements and biopsies of hepatogastric ligaments were performed at the time of surgery, circumcostal gastropexy, for correction of GDV. Serial sections from each ligament were stained with H&E, Masson's trichrome, and elastin stains to assess morphology, including smooth muscle, collagen, and elastic fiber contents. RESULTS--There were no differences observed by light microscopy in incidence or degree of histopathologic alterations between the 2 groups of dogs. The lengths of hepatogastric ligaments in GDV-affected dogs, however, were significantly longer than those of control dogs (GDV-affected dogs, 7.0 [5.0 to 9.5] cm median [range]; control dogs, 5.0 [3.0 to 7.5] cm median [range]; P = 0.01). CONCLUSIONS--Causality can not be inferred from this study. It is not known whether the ligaments were lengthened as a result of GDV or whether the lengthened ligaments predisposed dogs to GDV. CLINICAL RELEVANCE--This finding may reflect increased laxity of the supporting hepatogastric ligament in the right quadrant of the abdomen. An elongated ligament may permit increased stomach mobility and predispose dogs to partial or complete gastric volvulus.

Effect of acute gastric dilatation on gastric myoelectic and motor activity in dogs.

OBJECTIVE: To investigate the effects of experimentally induced acute gastric dilatation on electrical and mechanical activities of the stomach in dogs. ANIMALS: 7 healthy dogs. PROCEDURE: Electrodes and strain-gauge force transducers were implanted on the serosal surface of the antrum and pylorus. Eight days later, baseline gastric electrical and contractile activities were recorded. The dogs were anesthetized and mechanically ventilated to maintain normocapnia while the stomach was distended (intragastric pressure, 30 mm Hg) for 180 minutes, using a thin compliant bag. Gastric electrical and contractile activities were recorded again on days 1 and 10 after dilatation. Recordings were analyzed to determine gastric slow-wave frequency, slow-wave dysrhythmia, propagation velocity of slow-waves, coupling of contractions to slow waves, motility index on the basis of relative contractile amplitudes, and onset of contractions after a standardized meal. RESULTS: Electrical or contractile activities were not significantly different 18 hours after acute gastric dilatation (day 1). Arrhythmias were evident before and after gastric dilatation in dogs from which food was withheld and in dogs after consumption of a meal. CONCLUSIONS: Variables for assessing gastric electrical and contractile activities were unaffected 18 hours after acute gastric dilatation. CLINICAL RELEVANCE: Analysis of results of this study indicated that altered electrical and contractile activities in dogs with short-term gastric dilatation are not likely to be secondary to the process of acute gastric dilatation.

Effect of dietary phosphoric acid supplementation on acid-base balance and mineral and bone metabolism in adult cats.

Experimental evidence indicates that maintenance of urinary pH < or = 6.4 is the single most effective means of preventing feline struvite crystalluria or urolithiasis of noninfectious causes. This may be accomplished by dietary acidification, but must be moderated to avoid potential adverse effects of excessive acidification, including bone demineralization, negative calcium balance, potassium depletion, and renal disease. Effects of chronic dietary phosphoric acid supplementation on acid-base balance and on mineral and bone metabolism were investigated in adult, domestic cats. One group of 6 cats was fed a basal, naturally acidifying diet without added acidifiers, and another group of 6 cats was fed 1.7% dietary phosphoric acid. Changes observed during 12 months of study included development of noncompensated metabolic acidosis, increased urinary calcium excretion, and lower but positive calcium balance in cats of both groups. Urinary pH decreased in cats of both groups, but was significantly (P < 0.05) and consistently maintained < or = 6.4 in cats given dietary phosphoric acid. Urinary phosphorus excretion increased in cats of both groups, but was significantly (P < 0.05) greater in phosphoric acid-supplemented cats, leading to lower overall phosphorus balance as well. Potassium balance decreased in cats of both groups, but was only transiently negative in the phosphoric acid-supplemented cats midway through the study, and normalized at positive values thereafter. Plasma taurine concentration was not affected by dietary acidification, and remained well within the acceptable reference range for taurine metabolism. Double labeling of bone in vivo with fluorescent markers was followed by bone biopsy and histomorphometric measurement of several static and dynamic variables of bone formation. Overall indices of bone formation decreased in cats of both groups with age and confinement, but were not affected by dietary phosphoric acid supplementation. Dietary supplementation with phosphoric acid used as the principal inorganic P source to achieve moderate and stable degree of urinary acidification, did not appear over the course of 1 year, to have induced adverse effects on mineral, bone, or taurine balance in these adult domestic cats.

Clinical and laboratory findings associated with actual or suspected azoospermia in dogs: 18 cases (1979-1990).

Eighteen dogs were evaluated for azoospermia, 8 of which had sired pups. On the basis of history, physical examination, and various laboratory evaluations, the cause and site of azoospermia varied. Two dogs that had never sired pups had likely been azoospermic from puberty (congenital azoospermia). Two dogs were azoospermic as a result of tumors (Sertoli cell tumor and malignant astrocytoma of the pituitary gland). Deposits of IgG were observed in testicular biopsy samples, which suggested an auto-immune cause for azoospermia in 5 dogs. One of the 5 dogs with IgG deposits in testicular tissues also had evidence of immune-mediated thyroiditis. Culturing of microbes in the semen was not helpful in determining potential causes of azoospermia, and results did not correlate with organisms isolated from testicular biopsy samples or with the finding of inflammation in biopsy samples. Because 6 dogs had relatives with histories of reproductive dysfunction, inbreeding also must be considered when evaluating dogs for azoospermia.

Evaluation of results of preoperative urodynamic measurements in nine dogs with ectopic ureters.

Cytometrographic studies and urethral pressure profiles were performed to objectively assess the functional status of the urinary bladder and urethra in 9 dogs with congenital ectopic ureters. Functional abnormalities of the urinary bladder or urethra were detected in 8 of 9 (89%) dogs. Cystometrographic evidence of reduced bladder capacity was detected in 4 (44%) dogs, and abnormalities in urethral pressure profiles were consistent with urethral incompetence in 6 (67%) dogs. Dogs with urethral pressure profile abnormalities were treated with phenylpropanolamine hydrochloride, and the urethral pressure profile was reevaluated. Urethral pressure measurements obtained before surgery (3 dogs) and after phenylpropanolamine (6 dogs) were used to predict the likelihood of continence after surgery. Predicted outcomes included continence maintained without medication (3 dogs), continence maintained with phenylpropanolamine (2 dogs), and persistent incontinence despite phenylpropanolamine administration (4 dogs). After surgical repair of ectopic ureters, 2 of 9 (22%) dogs were continent without medication, and 2 (22%) maintained continence with phenylpropanolamine treatment. Various degrees of incontinence persisted in 5 of 9 (56%) dogs, 4 of which had urethral incompetence that had been documented as poorly responsive to phenylpropanolamine administration prior to surgery. Predicted outcomes were consistent with actual outcomes in 8 of 9 (89%) dogs, with predictions of incontinence proving accurate in 4 of 4 (100%) dogs and predictions of continence proving accurate in 4 of 5 (80%) dogs. Urodynamic assessment of dogs with ectopic ureters appears to be valuable for identifying concurrent functional abnormalities of the urinary bladder and urethra and for predicting postoperative outcome.

Distracted cervical spinal fusion for management of caudal cervical spondylomyelopathy in large-breed dogs.

Using an autogenous bone graft (obtained from the iliac crest), 4-mm cancellous bone screws, and polymethylmethacrylate, a distracted cervical spinal fusion technique was performed on 10 dogs with myelographic evidence of caudal cervical spondylomyelopathy. All dogs had evidence of dynamic soft tissue spinal cord compression, as indicated by flexion, extension, and traction myelographic views. Of the 10 dogs, 4 previously had undergone surgery by use of ventral slot or cervical disk fenestration techniques, and their neurologic status had deteriorated after the original surgery. Preoperative neurologic status of the 10 dogs included nonambulatory tetraparesis (n = 5), severe ataxia with conscious proprioceptive deficits (n = 2), and mild ambulatory ataxia with conscious proprioceptive deficits (n = 3). Five dogs had signs of various degrees of cervical pain. Clinical improvement was observed in 8 of 10 dogs--either improved neurologic status or elimination of cervical pain. Implant loosening developed in 3 dogs; 2 of them were euthanatized because of lack of neurologic improvement. Radiographic evidence of bony cervical fusion was observed during a 9- to 24-week period in 6 of the 8 surviving dogs. The distracted cervical fusion technique appears to be a valid surgical procedure to manage cervical spondylomyelopathy in those dogs in which the lesions are limited to one cervical intervertebral disk space.

Cholecystography and cholecystoduodenostomy in the diagnosis and treatment of bile duct obstruction in a dog.

A common bile duct obstruction was documented in a dog, by performing cholecystography haparoscopic visualization facilitated performance of the cholecystography. Target cells were a consistent hematologic finding. Cholecystoduodenostomy, an easily performed surgical technique, allowed for restoration of bile flow and resolution of clinical signs.

Globule leukocyte tumor involving the small intestine in a cat.

Globule leukocyte tumor involving the distal portion of the jejunum and proximal portion of the ileum caused chronic vomiting and weight loss in a 3-year-old cat. The intestinal mass was resected during exploratory laparotomy. The histologic appearance of the mass was characterized by inclusion of numerous intracytoplasmic eosinophilic granules. Similar cells were found in the mesenteric lymph node and were suggestive of metastasis. Tumor recurrence was not detected until 13.5 months after the surgery. The malignant but slow-growing nature of this tumor allowed a disease-free interval that exceeded 1 year, despite incomplete tumor resection.

Female pseudohermaphroditism in three sibling greyhounds.

Three 18-month-old Greyhound siblings were found to have female pseudohermaphroditism. The disorder in sexual differentiation likely developed because the dam received testosterone proprionate for estrus prevention. All 3 siblings had a prepuce (no penis), vagina, uterus, and ovaries.

Surgical techniques for the liver and biliary tract.

Surgical treatment of hepatic and biliary disease requires a thorough knowledge of pertinent anatomy and pathophysiology. Proper attention to both preoperative and postoperative care is important. This article describes many of the more common surgical manipulations of the liver and biliary tract, as well as pre- and postoperative considerations.

Conditions of the thoracolumbar spine.

Neurological deficits suggesting trauma to the spinal cord in the thoracolumbar area are the most common clinical presentation of neurosurgical conditions. By far, the most common cause of thoracolumbar spinal cord dysfunction is intervertebral disc disease. Disc herniation and subsequent spinal cord compression usually requires prompt medical treatment, then referral for high detail radiographs, myelogram, and surgical decompression. Other causes of thoracolumbar spinal cord dysfunction include neoplasia, discospondylitis, fibrocartilaginous embolism, and degenerative myelopathy.

Clinical evaluation of tube esophagostomy in small animals.

An alternative technique for placement of tube esophagostomy in small animals is described. Tube esophagostomy was placed in 13 dogs and nine cats. The mean duration of tube placement was 23 days (range, one to 48 days). No significant complications related to the tube were noted. In each case, tube esophagostomy was tolerated and time to healing of the esophagostomy site following tube removal was less than two weeks. Tube esophagostomy is suitable for use in a nutritionally compromised small animal with a functional esophagus and gastrointestinal tract.