Inhibition of intracellular hepatitis C virus replication by nelfinavir and synergistic effect with interferon-alpha.

Liver diseases associated with hepatitis C virus (HCV) infection have become the major cause of mortality in patients with human immunodeficiency virus (HIV) infection since the introduction of highly active anti-retroviral therapy. HCV-related liver disease is more severe in HIV-infected patients than in non-HIV-infected patients, but the standard therapies used to treat chronic hepatitis C in HCV/HIV coinfected patients are the same as those for patients infected with HCV alone. HIV protease inhibitors might have potential to down-regulate HCV load of HCV/HIV coinfected patients. In this study, we evaluated the effects of nelfinavir on intracellular HCV replication using the HCV replicon system. We constructed an HCV replicon expressing a neomycin-selectable chimeric firefly luciferase reporter protein. Cytotoxicity and apoptosis induced by nelfinavir were assessed and synergism between nelfinavir and interferon (IFN) was calculated using CalcuSyn analysis. Nelfinavir dose-dependently repressed HCV replication at low concentrations (IC(50), 9.88 micromol/L). Nelfinavir failed to induce cytotoxicity or apoptosis at concentrations that inhibited HCV replication. Clinical concentrations of nelfinavir (5 micromol/L) combined with IFN showed synergistic inhibition of HCV replication in our replicon model. Our results suggest that the direct effects of nelfinavir on the HCV subgenome and its synergism with IFN could improve clinical responses to IFN therapy in HCV/HIV coinfected patients.

Comparison of radiographic arthritic changes associated with two variations of tibial plateau leveling osteotomy.

Osteoarthritis (OA) progresses in the canine cranial cruciate ligament (CCL) deficient stifle. Progression of OA is also documented in canine patients after various surgical repair techniques for this injury. We evaluated the radiographic arthritic changes in canine stifle joints that have sustained a CCL injury, and compared radiographic OA scores between Tibial Plateau Leveling Osteotomy (TPLO)surgery patients receiving a medial parapatellar exploratory arthrotomy for CCL remnant removal versus those receiving a limited caudal medial arthrotomy without removal of the CCL remnants. Medial/lateral and caudal/cranial stifle radiographs were obtained before surgery, immediately following TPLO surgery and at 7-38 months (mean 20.5) after surgery. Sixty-eight patients (72 stifles) were included in the study. The cases were divided into two groups. The patients in group 1 (n = 49 patients, 51 stifles) had a limited caudal medial arthrotomy, and patients in group 2 (n = 19 patients, 21 stifles) had a medial parapatellar open arthrotomy. A previously described radiographic osteoarthritis scoring system was used to quantify changes in both of the groups. The age, weight, OA scores, initial tibial plateau angle, final tibial plateau angle, and the change in angle were compared between the groups. The results showed that there was significantly less progression of OA in the group that had the limited caudal medial, arthrotomy, versus a medial parapatellar open arthrotomy. There was a significant advancement of the OA scores of patients that had TPLO surgery.

Effects of carbon dioxide arterial infusion on hepatic biochemistry and histology in a rabbit model.

RATIONALE AND OBJECTIVES: The objective of this study was to determine the effect of carbon dioxide (CO2) infusion on hepatic biochemistry and histology in a rabbit model. METHODS: The study population consisted of 24 anesthetized rabbits that received hepatic infusion of either CO2 or saline (control) at doses of 10 mL/kg, comparable with those doses used in human clinical trials. Blood for clinical chemistry analysis was collected at baseline, 1 hour, 24 hours, and 168 hours (7 days) postprocedure. The rabbits were killed at 7 days postprocedure and the liver examined histologically for hepatic damage. RESULTS: There were no significant differences between the CO2 and the control groups in dorsal, ventral, and dorsal/ventral scores. Increases in alanine, an important indicator of hepatocellular membrane injury, in the CO2 group were significantly greater at 1 hour and 24 hours posttreatment (P = 0.037 and 0.013). However, the mean levels at 168 hours (7 days) were not significantly different (P = 0.22). The increases at 1 and 24 hours were small, transient, and considered clinically insignificant. CONCLUSION: No long-term hepatic effects in these animals were suggested by biochemical and histological examinations.

Sonographic evaluation of the common bile duct in cats.

Ultrasound is an excellent imaging tool in the evaluation of the biliary tract in cats. Extrahepatic obstruction could be diagnosed by the presence of dilated common bile duct (CBD), which was measured ventral to the portal vein in the porta hepatis. At this level, the diameter of the CBD in 6 healthy cats and in 22 cats with nonsurgical jaundice was < or = 4 mm. Six of 7 cats with a CBD > 5 mm had extrahepatic biliary obstruction.

Effect of radiographic positioning on interpretation of cubital joint congruity in dogs.

OBJECTIVE: To ascertain effects of x-ray beam centering and limb position on apparent congruity of a normal cubital joint (elbow). ANIMALS: 6 skeletally mature male Treeing Walker Coonhounds without physical, radiographic, or gross evidence of elbow abnormalities. PROCEDURE: Relative movement among humerus, radius, and ulna and measured joint space width on mediolateral and craniocaudal radiographic views was compared, using various x-ray beam centering and limb positions. RESULTS: Highest agreement and greatest certainty on subjective determination of congruity was for the flexed 90 degrees mediolateral radiographic view with the x-ray beam centered on the elbow. Distortion artifact of the proximal ulnar measurements was significant when the x-ray beam was centered on the midpoint of the radius. On the mediolateral view, the humeroradial joint space became significantly wide when the elbow was flexed. On the craniocaudal view, maximal humeroradial joint space width was obtained when the x-ray beam bisected the angle of the joint or was angled +30 degrees toward the humerus. CONCLUSIONS: Artifact distortion of joint width affected objective and subjective assessment of elbow congruity when the limb was placed in extreme flexion or extension or when the x-ray beam was not centered over the area of interest. Optimal visualization of the humeroradial joint space on the craniocaudal view was achieved when the x-ray beam bisected the angle of the elbow or was slightly angled toward the humerus. CLINICAL RELEVANCE: Elbow congruity was best assessed on the flexed 90 degrees lateral radiographic view with the x-ray beam centered on the joint.

Dorsal subluxation of the proximal interphalangeal joint in the pelvic limb of three horses.

In horses, dorsal subluxation of the proximal interphalangeal joint in the pelvic limb, which realigned when weight was applied to the limb, improved following surgery. Improvement was observed, if not immediately, at least within two weeks after treatment. The severity and duration of the condition appear to be important considerations in predicting the time necessary for resolution of the condition following surgery. Treatment consisted of surgical resection of a small segment of the medial head of the deep digital flexor tendon in the pelvic limb. The section removed was positioned distal to the tarsus, at the level prior to the tendon joining the main portion of the deep digital flexor tendon. Previously, a surgical treatment was described in which a portion of the accessory ligament (distal check ligament) of the deep digital flexor muscle was resected. Because the medial head is much stronger than the accessory ligament, resection of the tendon of the medial head provides more release of tension to allow stretching of the deep digital flexor muscle tendon.

Subcutaneous emphysema in a neonatal foal.

A 16-hour-old foal was examined because of subcutaneous emphysema, which began developing 3 hours after a routine delivery. Physical examination did not reveal soft-tissue or musculoskeletal trauma, and there were no skin injuries to explain the subcutaneous accumulation of air. Results of CBC and serum biochemical analysis were within reference limits, and findings on endoscopy of the pharyngeal area, trachea, and esophagus were within normal limits other than observation of dorsal pharyngeal compression. A pulmonary bulla, pneumomediastinum, and pneumothorax were detected on thoracic radiography. Because of the apparent association of the subcutaneous emphysema and thoracic abnormalities, a diagnosis of primary subcutaneous emphysema was made. A tracheostomy tube was placed to facilitate ventilation and to provide an exit point for the trapped air. Supportive care was provided. The foal's condition resolved over the subsequent 8 days.

Radiographic evaluation of elbow joints before and after surgery in dogs with possible fragmented medial coronoid process.

OBJECTIVE: To determine the usefulness of 5 radiographic projections of the elbow joint for identification of fragmented coronoid process (FCP) and associated secondary degenerative changes in dogs. DESIGN: Longitudinal clinical study. ANIMALS: 19 dogs suspected of having FCP (7 dogs, 1 elbow joint; 12 dogs, both elbow joints). PROCEDURE: 5 radiographic projections were obtained before and after surgery for all elbow joints on which exploratory arthrotomy was performed because of suspected FCP. Radiographs obtained before surgery were compared with radiographs obtained after surgery and radiographs taken of the excised fragments. Each projection was evalated for its utility in definitively identifying FCP and 7 specific degenerative changes. Interevaluator agreement, use of each radiographic projection for definitively identifying a feature, and ability of the 4 evaluators to definitively identify a feature were analyzed. RESULTS: The craniolateral-caudomedial oblique (Cr15L-CdMO) projection had a significantly higher sensitivity for definitively identifying FCP, compared with the other 4 projections. Interevaluator and kappa agreement for the 5 projections did not differ significantly among the 7 degenerative changes evaluated. The radiographic projection with the highest sensitivity and specificity for detection of a particular degenerative change varied by feature. CLINICAL IMPLICATIONS: Of the 5 radiographic projections evaluated, the Cr15L-CdMO projection provided the highest sensitivity and was the best projection to use for definitively identifying FCP. The craniocaudal, Cr15L-CdMO, and mediolateral projections most reliably allowed for identification of secondary degenerative changes.

Effect of reproductive status on feline renal size.

Renal length and width dimensions were determined from survey radiography and excretory urography in 28 cats of various sex and reproductive status. Renal dimensions were expressed as a ratio to the length of the second lumbar vertebra. Renal dimensions were not significantly different when males were compared to females. However, significant differences in renal dimensions between intact and neutered cats were identified. Renal length ratios for neutered cats were: left kidney 2.22 +/- 0.14 (mean +/- standard deviation), right kidney 2.29 +/- 0.14. In intact cats, renal length ratios were: left kidney 2.60 +/- 0.19, right kidney 2.65 +/- 0.24. The mean renal length ratios for neutered cats was smaller than previously reported normal values. Thus, reproductive status should be considered when evaluating feline kidneys for alterations in size. Based on this study, normal feline renal length ratios range from 1.9 to 2.6 for neutered cats and 2.1 to 3.2 for intact cats.