Cerebrospinal fluid response following metrizamide myelography in normal dogs: effects of routine myelography and postmyelographic removal of contrast medium

The effect of metrizamide myelography on 90-minute postmyelographic cerebrospinal fluid (CSF) samples was evaluated in a paired crossover study in 16 normal dogs. Each dog received a routine cervical myelogram (nonwithdrawal myelography) and a myelogram followed by contrast medium removal via aspiration from the subarachnoid space (withdrawal myelogram). Following nonwithdrawal myelography, the CSF was characterized by mild inflammation with a mixed pleocytosis and increased protein concentration. Compared with the nonwithdrawal CSF samples, the postmyelographic CSF of the withdrawal dogs had a more severe inflammatory response with significant increases (p < 0.05) in absolute numbers of neutrophils, monocytoid cells, eosinophils, lymphocytes, and protein concentration. The withdrawal procedure may have contributed an additional mechanical effect on the leptomeninges producing the more severe inflammatory response in the withdrawal dogs. Although seizure data are not reported here, postmyelographic seizures were more frequent following non-withdrawal myelography as compared with withdrawal myelography (p < 0.05), suggesting a decrease in metrizamide-induced neurotoxicity for the withdrawal dogs.     

Myelographic localization of spinal cord compression in dogs. A comparison between cisternal and lumbar injections of metrizamide "Amipaque" in diagnosing and locating spinal cord compression.

Metrizamide is a new water-soluble contrast medium possessing unique properties, one of which is that even in an isotonic solution it has a radiographic density sufficient for a diagnostic myelogram. Whereas in the past myelography with water-soluble preparations invariably entailed lumbar injections, which are technically difficult in dogs, the fact that isotonic metrizamide causes so little tissue irritation has made it possible to inject the contrast solution into the cisterna magna. The author has compared metrizamide myelograms obtained with both cisternal and lumbar injections. Myelography with a cisternal injection is preferable for demonstrating cervical cord compressions and also in cases in which it is desirable to obtain myelographic information on both the cervical and the thoraco-lumbar areas. If, on the other hand, it is necessary to determine exactly the extent of a thoraco-lumbar compression before decompressive laminectomy, the contrast should be injected in the lumbar region in such an amount and at a pressure high enough to ensure that the contrast is forced past the site of the compression. The safety of metrizamide will probably enable a better prognosis following surgery than was previously possible.     

Metrizamide myelography in sixty-eight dogs

The results of 68 metrizamide myelograms in the dog are recorded, involving both cisternal and lumbar punctures. The technical considerations are described together with interpretation of the normal myelogram and the diagnostic signs. Failure to obtain a good contrast column occurred in 14 dogs, and post myelographic signs were observed in eight.     

A COMPARISON OF IOPAMIDOL AND METRIZAMIDE FOR CERVICAL MYELOGRAPHY IN THE DOG

Cervical myelography using iopamidol, a new nonionic contrast medium, was studied in nine dogs. Postmyelographic seizure activity, motor evoked potentials, and rectal temperatures were monitored, and myelographic quality was subjectively evaluated. The results were compared with data from eight dogs that had metrizamide myelography. The iopamidol group had fewer seizures ( p < 0.01) but exhibited no difference in motor evoked potential or rectal temperature recordings. Myelographic quality was similar for iopamidol and metrizamide. The study suggests that iopamidol was less neurotoxic than metrizamide for canine cervical myelography.     

Prevention of postmetrizamide myelographic seizures in dogs, using 5% dextrose solution

Diuresis by IV administration of 5% dextrose in a balanced electrolyte solution (BES) reduced the frequency of occurrence of postmyelographic seizures in dogs. In the first study, a single myelogram was obtained in 8 dogs without dextrose diuresis. Two of these dogs weighed greater than 15 kg and both had seizures after metrizamide myelography. The remaining 6 dogs weighed less than 15 kg and only 2 had seizures. Greater body weight may have increased the risk of postmyelographic convulsions. In a crossover study, myelograms were obtained in 12 dogs weighing 20 to 31 kg. Six dogs were given 5% dextrose in BES (20 ml/kg of body weight/hr [diuresed]) and 6 were given BES alone (10 ml/kg/hr [not diuresed]). When myelography was repeated 10 days later, the 6 dogs that had been given 5% dextrose in BES were given BES only and the 6 dogs that had been given BES alone were given 5% dextrose in BES. The frequency of convulsions after metrizamide myelography was lower when dogs were given dextrose (33%) than when they were not (100%).     

STANDING MYELOGRAPHY IN THE HORSE USING A NONIONIC CONTRAST AGENT

Standing myelography in the horse has been previously described. In that study, metrizamide was used and significant complications were reported. In recent years, the introduction of less-toxic nonionic contrast media has reduced the incidence of complications. This study was undertaken to determine whether standing myelography using a nonionic contrast medium could provide a diagnostic study and be performed safely in the equine patient. Standing myelography was performed in eight horses. The contrast medium used was iohexol. In five horses a myelogram of diagnostic quality was achieved; in one horse contrast flowed only to the level of C6 and in two horses contrast medium did not reach the cervical subarachnoid space. Owing to the difficulty in achieving good flow of the contrast medium in some horses, this procedure may be of limited utility. However, if puncture of the lumbosacral subarachnoid space can be achieved easily and quickly, standing myelography may be a clinically useful procedure. It may be attempted in cases in which the economic value of the patient makes myelography under general anesthesia impractical. In patients presenting for evaluation of ataxia it may be possible to perform a standing myelogram at the time of CSF sample collection from the lumbosacral space.     

A PROSPECTIVE CLINICAL TRIAL COMPARING METRIZAMIDE AND IOHEXOL FOR EQUINE MYELOGRAPHY

A prospective clinical trial comparing adverse postmyelographic effects and myelographic quality of metrizamide and iohexol was conducted. Using a predetermined, randomized assignment, 24 horses exhibiting neurologic signs were administered either metrizamide (180 mgl/ml) or iohexol (180 mgl/ml) via cerebellomedullary puncture. Each horse was evaluated postmyelographically for adverse effects. Myelographic quality was assessed by a numerical scoring method. Adverse effects were observed more frequently with metrizamide (21) compared with iohexol (6) myelography (p < 0.05). Seizures, intensification of preexisting neurologic signs and prolonged anesthetic recovery were the most common complications after myelography. There was no difference in myelographic quality (p > 0.05). We conclude that iohexol is safer than metrizamide for equine myelography and that quality myelograms can be obtained with either contrast medium.     

Neurotoxicologic effects of the nonionic contrast agent iopamidol on the leptomeninges of the dog

The effect of iopamidol on the leptomeninges was tested and compared with that of metrizamide and normal saline solution in 18 dogs. Pathologic and clinical effects were evaluated at 24 hours and 14 days after cisternal injection of iopamidol, metrizamide, or normal saline solution. Pathologic changes were evaluated by microscopic examination of serial CSF samples and of sections of brain and spinal cord with the leptomeninges intact. Clinical changes were subjectively evaluated. Electromyograms and EEG were performed on each dog after physical and neurologic examination. There were no changes seen in neurologic status, electromyogram, or EEG in any of the dogs immediately after subarachnoid injection nor at 24 hours or 14 days later. Pathologic changes were limited to mild, moderate, or severe patchy hemorrhagic leptomeningitis seen at 24 hours after iopamidol or metrizamide was injected. The severity of changes were judged to be similar with both these agents. The CSF analysis and histologic evaluation of brain and spinal cord sections revealed a neutrophilic response to iopamidol and a mononuclear response to metrizamide. These findings indicate that iopamidol has minimal neurotoxicologic effect on the leptomeninges and therefore has merit as a myelographic agent.     

EFFECTS OF METRIZAMIDE MYELOGRAPHY ON CEREBROSPINAL FLUID ANALYSIS IN THE DOG

The effect of metrizamide myelography on the composition of cerebrospinal fluid (CSF) was studied. Seven dogs received an intracisternal injection of metrizamide. An intracisternal puncture was performed in three additional dogs that did not receive metrizamide. CSF was collected before myelography and 24, 72, and 144 hours after myelography from all dogs. A significant increase in the percentage of neutrophils (p<0.05) and a pleocytosis noted 24 hours after myelography (p<0.02) were attributed to the effect of metrizamide. Significant increases in total protein concentration (p<0.001) and erythrocyte count (p<0.05), and a decrease in the percentage of small mononuclear cells (p<0.01) were attributed to repeated intracisternal puncture. No significant changes were observed for CSF creatine phosphokinase activity or the percentage of large mononuclear cells.     

Use of pentobarbital sodium to reduce seizures in dogs after cervical myelography with metrizamide

We conducted a prospective study to examine the effect of pentobarbital administration on the development of seizures in dogs that had undergone cervical myelography with metrizamide while anesthetized with halothane. Thirty dogs scheduled for cervical myelography were assigned to 3 groups. Dogs in group 1 received no pentobarbital. Those in group 2 were administered pentobarbital (5 mg/kg, IM) before induction of anesthesia, and those in group 3 received pentobarbital at the end of the procedure when the anesthetic vaporizer was turned off. Anesthesia was induced with thiamylal sodium in all dogs and was maintained with halothane. Dogs that underwent surgery immediately after the myelography were not included in the study. A significant difference was not found among the 3 groups in terms of number of dogs that had seizures, mean body weight of the dogs, duration of anesthesia after injection of metrizamide, time from extubation to first seizure, volume of metrizamide injected, or clinician performing the myelography.     

STANDING MYELOGRAPHY IN SIX ADULT HORSES

Standing myelography was conducted in six neurologically normal adult horses. Myelograms were performed without general anesthesia or tranquilization. Four horses were premedicated orally with 2.2 milligrams/kilogram (mg/kg) of phenobarbital 16 hours and 4 hours prior to myelography to raise their seizure threshold. One-hundred milliters (ml) of cerebral spinal fluid (CSF) was withdrawn from the lumbosacral space prior to injection. Approximately 100 ml of technical grade metrizamide * was injected into the subarachnoid space via a lumbosacral tap. After injection the horse's head was lowered for approximately 10 minutes to facilitate cranial movement of the metrizamide. Lateral cervical radiographs were taken in a standing position. Filling of the subarachnoid space in the cranial cervical region was good to excellent in five horses. In one horse there was poor definition of the cranial cervical region. There was good to excellent filling of the subaranoid space in the caudal cervical region in all six horses. Reactions to metrizamide injection varied. The most severe reaction was generalized seizure.     

IOHEXOL MYELOGRAPHY IN THE DOG

Myelography with iohexol (180 mg iodine/ml, 0.25 ml/kg), a new nonionic radiologic contrast medium, was performed in 100 dogs of 33 different breeds. In 96 of the dogs the iohexol mixed evenly with the cerebrospinal fluid, providing an homogeneous, continuous column of contrast medium within the subarachnoid space, and a radiologic diagnosis of a normal myelogram or disease involving the spinal cord was made. Pooling of iohexol in the dorsal part of the subarachnoid space occurred in four dogs; whether this was related to poor mixing of contrast medium with cerebrospinal fluid or disease of the spinal cord and meninges requires further study. Postmyelographic signs of central nervous system irritation (fasciculations of the temporal muscles and three episodes of seizure activity) were observed in only one dog and were controlled with diazepam. The presenting neurologic signs were aggravated after myelography in four other dogs, two of which were eventually killed. This study provided further evidence of the increased safety of iohexol compared with metrizamide, the first of the nonionic media, as a contrast medium for myelography in the dog.     

COMPLICATIONS OF METRIZAMIDE MYELOGRAPHY IN THE DOG: A SUMMARY OF 107 CLINICAL CASE HISTORIES

The case histories of 107 dogs undergoing metrizamide myelography at two veterinary hospitals were reviewed. Twenty-three variables, including body weight, injection site, dose of contrast medium, and medical complications during and after recovery from anesthesia, were submitted to statistical analysis by computer. Partial or generalized seizures were the most common medical complications, occurring in 54 percent of the dogs weighing more than 29 kg. Other less frequent medical complications were exacerbation of neurologic signs the day following myelography (11 percent), transient apnea during contrast medium injection (9 percent), vomiting (5 percent), hyperesthesia (3 percent), pyrexia (1 percent), and death (1 percent). The incidence of medical complications associated with metrizamide myelography in this study is higher than in previous reports. The most likely variables associated with seizures were high injection volumes and metrizamide injection at the cisterna magna. The preanesthetic administration of intramuscular pentobarbital did not significantly reduce seizure incidence. Seizures were controlled by anticonvulsant medication.     

Intra-articular tissue response to analytical grade metrizamide in dogs

The effect of analytical grade metrizamide (AM) injected into the canine stifle, for purposes of arthrography, was studied in 12 adult dogs using saline solution as the control solution injected into the contralateral joints. The AM was used at a concentration of 280 mg of iodine/ml and was administered at the dose of 0.3 ml/cm thickness of the stifle joint. For each joint, arthrocentesis was done before and 7 days after injection of either the contrast medium or saline solution. Physical, biochemical, and cytologic examinations were done on the synovial fluid while the synovial membranes and femoral articular cartilages were sectioned, stained, and examined for histopathologic changes. At the 95% confidence level, significant differences in the total and differential mononuclear cell counts were not seen between the AM- and saline solution-injected joints. However, some subtle changes in the synovial membranes were observed. Intra-articular injection of AM or saline solution initiated a mild inflammatory response, the AM causing slightly more response than the saline solution.     

Comparison of metrizamide and iohexol for cisternal myelographic examination of dogs

A double-blind study, using metrizamide, iohexol, or Ringer's solution (control) as cisternal myelographic agents, was performed on 25 dogs. Before myelographic examination was done, each dog was subjected to physical, clinical pathologic, and neurologic examinations, as well as examinations by electroencephalography and computerized tomography. These were repeated 24 hours after completion of the myelographic examination. The group of dogs given metrizamide (group II) had a significantly greater occurrence of seizure activity (6 of 10) than did the control dogs (group I; 0 of 5) or dogs given iohexol (group III; 0 of 10; P less than 0.003). In group II, the CSF microprotein concentration was significantly greater 24 hours after myelography was done than were the values in groups I and III (P less than 0.003). Myelograms of the group II dogs (metrizamide) and group III dogs (iohexol) had similar diagnostic qualities. At 24 hours after myelographic examination was done, computerized tomography scan revealed that each dog given metrizamide and iohexol had myelographic contrast material in the brain and cervical spinal cord parenchyma. Seemingly, iohexol has good diagnostic quality, but is less epileptogenic than metrizamide when used in cervical myelographic examinations of dogs.     

Anti-tumor effect of adenoviral vector-mediated p53 gene transfer on the growth of canine osteosarcoma xenografts in nude mice

We evaluated the anti-tumor effect of adenoviral vector-mediated p53 gene therapy on the growth of canine osteosarcoma xenografts formed in nude mice. Nude mice were subcutaneously transplanted with cells of 2 P53 mutant canine osteosarcoma cell lines, POS and CHOS. The osteosarcoma xenografts were injected with either an adenoviral vector that expresses canine wild-type P53 (AxCA-cp53) or LacZ (AxCA-LacZ). Tumor growth was significantly inhibited in the xenografts injected with AxCA-cp53 in comparison to those injected with AxCA-LacZ or PBS during the observation period of 27 days. An increase of the amount of p21(WAF1/CDKN1A) mRNA, and the number of apoptotic cells was shown in the tumors injected with AxCA-cp53 in comparison to those injected with AxCA-LacZ or PBS. The present study revealed that the adenoviral vector-mediated p53 gene transfer had an anti-tumor effect in canine osteosarcoma xenografts formed in nude mice.     

Changes in the Aerobic Vaginal Bacterial Mucous Load after Treatment with Intravaginal Sponges in Anoestrous Ewes: Effect of Medroxiprogesterone Acetate and Antibiotic Treatment Use

Intravaginal sponges (IS) impregnated with progestagens are widely used for oestrous synchronization in ewes. As progestogens depress the immuno response, the first aim was to determine whether medroxiprogesterone acetate (MAP) content affects the vaginal bacteria number (VBN) in IS‐treated anoestrous ewes. The second aim was to compare the effectiveness of different antibiotic treatments to control the VBN increase caused by IS. In both experiments, IS were inserted during 14 days in anoestrous ewes. In the first, 11 ewes received commercial sponges (50 mg MAP), and 10 ewes received placebo sponges. For the second experiment, IS were inserted in three groups (n = 12/group), containing oxytetracycline im (20 mg/kg); injected into the sponge (0.02 mg), or control (no antibiotic). At sponge withdrawal, all ewes received 300 UI eCG. Mucous samples were collected from the vagina before sponge insertion, at sponge withdrawal, 24, 48 and 72 h later, and the VBN (colony‐forming units per ml; CFU/ml) was counted after 48‐h incubation. Medroxiprogesterone content did not affect VBN (log CFU/ml: 4.3 ± 0.2 vs 4.4 ± 0.2 with and without MAP, respectively). Bacterial number increased from 3.5 ± 0.2 at sponge insertion to 6.9 ± 0.1 at sponge withdrawal (p < 0.0001) and decreased the following day to 4.3 ± 0.2 (p < 0.0001). In the second experiment, VBN increased at sponge withdrawal (p < 0.0001) in all groups and decreased the following day (p < 0.0001). The CFU/ml at sponge withdrawal was lower in ewes treated with antibiotics (p < 0.0001), being even lower when local rather than systemic antibiotic was administered (log CFU/ml: 3.3 ± 1.8 vs 7.2 ± 1.8). The day of oestrous VBN was similar for all treatments and similar to that observed before sponge insertion. We concluded that MAP does not influence the increase in VBN, as the main effect is provoked by the sponge device itself, and local antibiotic treatment resulted in a lower bacterial growth than systemic treatments.     

氟苯尼考注射液在鸡体内残留消除研究

［摘 要］为研究氟苯尼考注射液在鸡体内的残留消除规律。本实验采用35只约3kg左右的健康白羽鸡,随机分为2组,给药组30只,对照组5只。给药组用药量为20mg/kg/次,每隔48小时用药1次,连用2次,对照组不给任何抗菌药物,与给药组同环境饲养。在最后一次给药6h、24h(1天)、72h(3天)、120h(5天)、168h(7天)时采集肉、肝、肾、皮脂样本,经LC-MS/MS法测定组织中的氟苯尼考及其标示物氟苯尼考胺残留量,并利用WT1.4软件计算休药期。结果显示：氟苯尼考注射液在鸡肌肉、肝脏、肾脏及皮脂中的休药期分别是3.41d、2.06d、2.25d、1.47d。为保证兽药使用安全、消费者健康和食品安全,推荐氟苯尼考注射液在鸡体内的休药期为4d。     

Evaluation of analytical grade of metrizamide for canine stifle arthrography

The use of analytical grade of metrizamide as contrast material in canine stifle arthrography was evaluated in 27 stifle joints. A concentration of 280 mg of I/100 ml was prepared, and the material was injected at a rate of 0.3 ml/cm thickness of the lateral to medial measurement. Acceptable arthrograms were produced in 22 (81.5%) cases. The mediolateral radiographic view was useful in demonstrating the cranial and caudal cruciate ligaments, the infrapatellar fat pad, and the tendon of the long digital extensor muscle. The caudocranial radiographic view was useful in demonstrating the medial and lateral menisci, the articular surfaces of the femoral condyles, and the outline of the joint capsule. Radiographs made within 15 minutes after injection of the contrast medium were acceptable, thus setting this period as the limit for obtaining useful arthrograms. The double contrast technique was found to be of little value.     

血虫净缓释剂的研制及预防鸡卡氏住白细胞虫病效果的评价

采用缓释剂制备技术研制了血虫净缓释注射液，该制剂药物包裹量大，析出量小，粘度均匀，3000r/min离心15分种不分层，且粘度小，便于肌肉注射使用。用含4％血虫净的缓释注射液，以0.5mL只和1mL／只的量分别注射50只110日龄健康海兰白鸡。结果用以上两种剂量给鸡注射，都可有效预防本病一个月，而同时对照的含4％血虫净的水溶剂组没有预防作用。