HTLV-1 cell lines differ in constitutively activated signaling pathways that can be altered by cytokine exposure.

Examination of signaling pathways used by HTLV-1-infected rabbit cell lines revealed differences between one, RH/K30, that mediates asymptomatic infection and another, RH/K34, that causes lethal experimental leukemia. Both lines are IL-2 independent; RH/K30 produces IL-4 while RH/K34 produces IL-10. Examination of the Jak/STAT (Janus kinase/signal transducer and activator of transcription) activation of the lines revealed constitutive phosphorylation of Jak1 in both STAT6 phosphorylation, not previously reported for HTLV-1 cells, was observed in RH/K30; STAT1 and STAT3 were phosphorylated in RH/K34. Treatment with cytokines altered the activation of the STAT proteins: IL-2 induced STAT5 phosphorylation in both lines. Supernatant from RH/K34 or IL-10 induced STAT3 phosphorylation in RH/K30 cells. Supernatant from RH/K30 or IL-4 induced STAT6 phosphorylation in RH/K34 cells, which could be reversed with a Jak kinase inhibitor--AG-490.

Paranasal sinus surgery through a frontonasal flap in sedated, standing horses.

OBJECTIVE: To report experience with paranasal sinus surgery through a frontonasal flap in sedated, standing horses. STUDY DESIGN: Treatment of 10 horses with naturally occurring paranasal sinus disease through a frontonasal bone flap created with the horses standing. ANIMALS: Ten adult horses. METHODS: After restraint and sedation, local anesthetic was injected subcutaneously along the proposed incision line over the conchofrontal sinus and was instilled into the sinuses through a small hole created in the frontal bone. A 3-sided, rectangular, cutaneous incision that extended through the periosteum was created over the frontal and nasal bones. The incision was extended into the conchofrontal sinus using a bone saw, and the base of the flap, on the midline of the face, was fractured. The sinuses were explored, and the horse was treated for the disease encountered. The flap was repositioned; subcutaneous tissue and skin were sutured separately. RESULTS: The horses had few signs of discomfort during creation of the bone flap and during disease treatment. Diseases encountered included inspissated exudate in the ventral conchal sinus (five horses), feed and exudate throughout the sinuses (one horse), occlusion of the nasomaxillary aperature (one horse), polyp (one horse), osteoma (one horse), and progressive ethmoidal hematoma (one horse). CONCLUSION: In selected cases, surgery of the paranasal sinuses can be performed safely on sedated and standing horses through a frontonasal bone flap. CLINICAL RELEVANCE: Performing surgery through a frontonasal bone flap with the horse standing and sedated, rather than anesthetized, eliminates risks and expense of general anesthesia.

Treatment response and athletic outcome of foals with tarsal valgus deformities: 39 cases (1988-1997).

OBJECTIVE: To evaluate the response to various treatments and long-term outcome of foals with tarsal valgus deformities. DESIGN: Retrospective study. ANIMALS: 39 foals with tarsal valgus deformities. PROCEDURE: Data collected from medical records, included signalment, history, reason for admission, and clinical findings. Radiographic views of the tarsus were evaluated for incomplete ossification of tarsal bones and were classified as normal in appearance, type-I incomplete ossification, or type-II incomplete ossification. Treatment and athletic outcome were documented for each foal. RESULTS: Radiographic assessment revealed that 22 of 39 foals (56%) had concomitant tarsal valgus deformities and incomplete ossification of the tarsal bones. Eight of 19 foals with tarsal valgus deformities that were treated with periosteal stripping responded favorably. Foals < or = 60 days old were significantly more likely to respond to periosteal stripping than older foals. Five of 8 foals with tarsal valgus deformities that were treated with growth plate retardation responded favorably. Eleven of 21 foals with long-term follow-up performed as intended. Compared with foals with type-II incomplete ossification, foals with tarsal bones that had a normal radiographic appearance or type-I incomplete ossification were significantly more likely to perform as intended. CONCLUSIONS AND CLINICAL RELEVANCE: Foals with tarsal valgus deformities should have lateromedial radiographic views of the tarsus obtained to assess the tarsal bones for incomplete ossification, which will affect athletic outcome. Because foals with type-II incomplete ossification of the tarsal bones respond poorly to periosteal stripping alone, treatment by growth-plate retardation is recommended.

Detomidine-propofol anesthesia for abdominal surgery in horses.

OBJECTIVE: To evaluate propofol for induction and maintenance of anesthesia, after detomidine premedication, in horses undergoing abdominal surgery for creation of an experimental intestinal adhesion model. STUDY DESIGN: Prospective study. ANIMALS: Twelve horses (424 +/- 81 kg) from 1 to 20 years of age (5 females, 7 males). METHODS: Horses were premedicated with detomidine (0.015 mg/kg i.v.) 20 to 25 minutes before induction, and a propofol bolus (2 mg/kg i.v.) was administered for induction. Propofol infusion (0.2 mg/kg/min i.v.) was used to maintain anesthesia. The infusion rate was adjusted to maintain an acceptable anesthetic plane as determined by muscle relaxation, occular signs, response to surgery, and cardiopulmonary responses. Oxygen (15 L/min) was insufflated through an endotracheal tube as necessary to maintain the SpO2 greater than 90%. Systolic (SAP), mean (MAP), and diastolic (DAP) arterial pressures, heart rate (HR), electrocardiogram (ECG), respiratory rate (RR), SpO2 (via pulse oximetry), and nasal temperature were recorded at 15 minute intervals, before premedication and after induction of anesthesia. Arterial blood gas samples were collected at the same times. Objective data are reported as mean (+/-SD); subjective data are reported as medians (range). RESULTS: Propofol (2.0 mg/kg i.v.) induced anesthesia (mean bolus time, 85 sec) within 24 sec (+/-22 sec) after the bolus was completed. Induction was good in 10 horses; 2 horses showed signs of excitement and these two inductions were not smooth. Propofol infusion (0.18 mg/kg/min +/- 0.04) was used to maintain anesthesia for 61 +/- 19 minutes with the horses in dorsal recumbency. Mean SAP, DAP, and MAP increased significantly over time from 131 to 148, 89 to 101, and 105 to 121 mm Hg, respectively. Mean HR varied over time from 43 to 45 beats/min, whereas mean RR increased significantly over anesthesia time from 4 to 6 breaths/min. Mean arterial pH decreased from a baseline of 7.41 +/- 0.07 to 7.30 +/- 0.05 at 15 minutes of anesthesia, then increased towards baseline values. Mean PaCO2 values increased during anesthesia, ranging from 47 to 61 mm Hg whereas PaO2 values decreased from baseline (97 +/- 20 mm Hg), ranging from 42 to 57 mm Hg. Muscle relaxation was good and no horses moved during surgery: Recovery was good in 9 horses and acceptable in 3; mean recovery time was 67 +/- 29 minutes with 2.4 +/- 2.4 attempts necessary for the horses to stand. CONCLUSIONS: Detomidine-propofol anesthesia in horses in dorsal recumbency was associated with little cardiovascular depression, but hypoxemia and respiratory depression occurred and some excitement was seen on induction. CLINICAL RELEVANCE: Detomidine-propofol anesthesia is not recommended for surgical procedures in horses if dorsal recumbency is necessary and supplemental oxygen is not available (eg, field anesthesia).

Isolation and mapping of the rabbit DM genes.

Proper peptide presentation by major histocompatibility complex (MHC)-encoded class II antigens is dependent on the products of the MHC DM loci. We identified the rabbit orthologues (RLA-DMA and -DMB) of human HLA-DMA and -DMB and found that they have 76.9% and 78.8% identity with HLA-DMA and -DMB, respectively. Like classical class II MHC genes, RLA-DM genes are more closely related to human HLA-DM genes than to mouse H2-DM. Among the DM family, there is a high degree of variability at the amino terminus of the DMa chains, and length variability in the cytoplasmic tails of both DMalpha and DMbeta. The rabbit DM genes are coexpressed with class II genes in lymphoid tissues, as are the DM genes of other mammals. The RLA-DM locus maps to the class II region of the rabbit MHC, and is flanked by the DP and DOB loci. Despite having some similarities to class II genes of bony fishes, the DM family represents a separate branch of the MHC class II family.

Deep digital flexor tenotomy as a treatment for chronic laminitis in horses: 35 cases (1988-1997)

OBJECTIVE: To determine long-term prognosis for horses with laminitis treated by deep digital flexor (DDF) tenotomy and to identify factors affecting success of the surgical procedure. DESIGN: Retrospective study. ANIMALS: 35 horses with laminitis treated by DDF tenotomy between 1988 and 1997. PROCEDURE: Information was obtained from individual medical records and follow-up telephone interviews with owners and referring veterinarians. Cumulative proportions of horses that survived 6 months and 2 years after tenotomy were determined. Effect of Obel grade of lameness on 6-month and 2-year survival and effect of distal phalangeal rotation on survival and future performance were evaluated by chi 2 analysis. Body weights of horses that survived > or = 2 years were compared with those of horses that survived < 2 years by ANOVA. RESULTS: 27 of the 35 (77%) horses survived > or = 6 months, and 19 of 32 (59%) survived > 2 years. Obel grade of lameness and body weight at time of surgery had no effect on 6-month or 2-year survival. Degree of distal phalangeal rotation had no effect on 2-year survival or the ability of horses to be used for light riding. Twenty-two of the 30 (73%) owners interviewed indicated they would have the procedure repeated on their horses given similar circumstances. CLINICAL IMPLICATIONS: DDF tenotomy is a viable alternative for horses with laminitis refractory to conventional medical treatment. In some instances, the procedure may be effective in returning horses to light athletic use.

Rectal stricture in an ostrich (Struthio camelus).

Exploratory celiotomy of an 18-mo-old female ostrich (Struthio camelus) with anorexia, lethargy, and constipation of 5 days' duration showed mesenteric volvulus and a focal narrowing of the rectum approximately 28 cm cranial to the cloaca. The prognosis was poor and the animal was euthanized. Necropsy revealed a fibrinonecrotic proctitis and a 3-cm-long circumferential stricture of the rectum. Histologically, the rectal wall at the stricture was deeply effaced by fibrovascular connective tissue with vascular thrombosis and necrotizing vasculitis, and it resembled the lesions in feeder pigs with fibrinonecrotic colitis.

Traumatic dental disease and soft tissue injuries of the oral cavity.

Trauma to the oral cavity can result in an array of injuries affecting teeth, bone, and soft tissue. A thorough examination of the oral cavity is often facilitated by employing a full-mouth speculum after the horse has been tranquilized. Identification of broken, loose, or split teeth; fractures of the premaxilla or mandible; and avulsion or laceration of soft tissue structures such as the lips or tongue is usually straightforward. Treatment options vary depending on the structure involved; however, appropriate treatment generally results in a functional and cosmetically acceptable end result.

Rabbit cells expressing human CD4 and human CCR5 are highly permissive for human immunodeficiency virus type 1 infection.

To evaluate the feasibility of using transgenic rabbits expressing CCR5 and CD4 as a small-animal model of human immunodeficiency virus type 1 (HIV) disease, we examined whether the expression of the human chemokine receptor (CCR5) and human CD4 would render a rabbit cell line (SIRC) permissive to HIV replication. Histologically, SIRC cells expressing CD4 and CCR5 formed multinucleated cells (syncytia) upon exposure to BaL, a macrophagetropic strain of HIV that uses CCR5 for cell entry. Intracellular viral capsid p24 staining showed abundant viral gene expression in BaL-infected SIRC cells expressing CD4 and CCR5. In contrast, neither SIRC cells expressing CD4 alone nor murine 3T3 cells expressing CCR5 and CD4 exhibited significant expression of p24. These stably transfected rabbit cells were also highly permissive for the production of virions upon infection by two other CCR5-dependent strains (JR-CSF and YU-2) but not by a CXCR4-dependent strain (NL4-3). The functional integrity of these virions was demonstrated by the successful infection of human peripheral blood mononuclear cells (PBMC) with viral stocks prepared from these transfected rabbit cells. Furthermore, primary rabbit PBMC were found to be permissive for production of infectious virions after circumventing the cellular entry step. These results suggest that a transgenic rabbit model for the study of HIV disease may be feasible.

Buccal absorption of etomidate from a solid formulation in dogs.

UNLABELLED: Etomidate is typically administered i.v. for the induction of general anesthesia. We believe that oral transmucosal absorption may extend etomidate's use to premedication and conscious sedation. Our objective was to study the oral mucosal absorption kinetics and bioavailability of etomidate in a solid dose form in dogs. A solid dose form containing 50 mg of etomidate in sorbitol for buccal administration was prepared. Each dog was administered both i.v. etomidate and buccal etomidate on separate days. Serum etomidate concentrations after i.v. administration were fit to a two-compartment pharmacokinetic model. The rates at which etomidate enters the systemic circulation via buccal mucosal absorption were calculated from serum concentrations from mucosal and i.v. administrations using model-dependent constrained numerical deconvolution. The apparent permeability coefficient and bioavailability were also determined. The mean (+/- SD) maximal serum etomidate concentration after buccal mucosal absorption from the 50-mg dose unit was 239 +/- 79 ng/mL. The time to reach maximal serum concentration was 12.5 +/- 1.8 min. Peak absorption rate of etomidate into the systemic circulation was 832 +/- 417 microg/min. For all dogs, 90% or more of the absorption via buccal mucosa took place during the period in which the drug was in contact with the mucosa (15 min). The apparent transbuccal mucosal permeability coefficient was 9.1 +/- 4.2 x 10(-4) cm/s, higher than values of any other compounds examined. Bioavailability calculated using the area under the serum etomidate concentration versus time curve method and the deconvolution method was 13.6% +/- 10.7% and 16.6% +/- 7.6%, respectively. In conclusion, etomidate is highly permeable through the canine buccal mucosa. IMPLICATIONS: Etomidate is highly permeable through the canine buccal mucosa. Both the onset and the termination of buccal mucosal absorption of etomidate are rapid, which suggests that titratable delivery of etomidate may be possible by buccal administration.

Evaluation of postoperative peritoneal lavage in standing horses for prevention of experimentally induced abdominal adhesions.

OBJECTIVE: To evaluate the postoperative use of peritoneal lavage for prevention of experimentally induced intraabdominal adhesions in horses. STUDY DESIGN: Areas of serosal abrasion were created on the jejunum of 12 horses. Postoperatively, six horses had peritoneal lavage, and six horses did not (controls). The number of adhesions was determined at necropsy 2 weeks after surgery. ANIMALS OR SAMPLE POPULATION: 12 horses. METHODS: Five sites of jejunal serosal abrasion were created in each horse. A 32 French thoracic catheter was placed into the right ventral aspect of the abdomen before closure of the abdominal incision. Treated horses had abdominal lavage with 10 L of lactated Ringer's solution on four occasions, then catheters were removed from all horses 34 hours after celiotomy. Horses were necropsied at 2 weeks to quantify the number of intraabdominal adhesions. RESULTS: All control horses and one treated horse developed intraabdominal adhesions. The number of adhesions was significantly less (P < .0293) in treated horses. No adverse inflammatory reactions appeared to be associated with repeated peritoneal lavage using lactated Ringer's solution or use of an abdominal drain. CONCLUSIONS: Peritoneal lavage reduced the frequency of intraabdominal adhesions. CLINICAL RELEVANCE: When postoperative adhesions are likely to develop, postoperative peritoneal lavage may decrease the frequency of adhesion formation.

Incomplete urethral obstruction associated with dilatation of the urethra, cystitis, and pyelonephritis in a Vietnamese pot-bellied pig.

A 2-year-old castrated male vietnamese pot-bellied pig examined because of stranguria was found to have severe dilatation and inflammation of the pelvic portion of the urethra accompanied by cystitis and pyelonephritis. The pig had apparently had chronic inflammation of the urinary tract that eventually progressed to incomplete obstruction of the urethra. However, the initial cause of the urinary tract inflammation could not be determined. Possible causes included chronic bacterial infection, traumatic injury during urethral catheterization, and injury to the urethral mucosa secondary to extreme acidification of the urine.

Effects of high-dose gentamicin sulfate on neuromuscular blockade in halothane-anesthetized horses.

OBJECTIVE: To evaluate effects of a single high dose of gentamicin on neuromuscular function in horses anesthetized with halothane. ANIMALS: 6 healthy adult horses. PROCEDURE: Halothane-anesthetized horses were positioned in left lateral recumbency, and the right hind limb was immobilized in a reusable fiberglass cast fixed to a steel frame. The hoof was attached to a force transducer, and resting tension of 0.93 +/- 0.16 kg was maintained. A supramaximal train-of-four stimulus of 2 Hz for a duration of 0.25 millisecond was applied to the superficial peroneal nerve every 20 seconds by a square-wave stimulator. The force of the evoked digital extensor tension was recorded to determine first muscle twitch tension, compared with the baseline value (T1%) and the ratio of the force of the fourth twitch to the first twitch (T4/T1). Data were recorded at 5, 10, 15, 30, and 60 minutes after i.v. administration of vehicle or gentamicin (6 mg/kg of body weight). RESULTS: There was a significant (P = 0.04) treatment-time interaction for the effect of gentamicin on T1%; T1% associated with vehicle decreased from 100% to 92% during the 60- minute study period, but no decrease was associated with gentamicin. For T4/T1, there was no significant effect of treatment or time or treatment-time interaction between gentamicin and vehicle. CONCLUSIONS: Gentamicin did not cause a decrease in initial muscular strength, nor did it impair the muscles' ability to sustain strength. CLINICAL RELEVANCE: A single high dose of gentamicin does not cause significant neuromuscular blockade when administered alone to healthy horses anesthetized with halothane.

Effects of postoperative peritoneal lavage on pharmacokinetics of gentamicin in horses after celiotomy.

OBJECTIVE: To evaluate the effect of peritoneal lavage on pharmacokinetics of gentamicin sulfate in healthy horses after experimental celiotomy. ANIMALS: 13 clinically normal horses. PROCEDURE: Horses were randomly assigned to control or experimental groups. All horses received gentamicin (6.6 mg/kg of body weight, IV, q 24 h) before surgery, underwent experimental abdominal surgery, and had abdominal drains placed percutaneously. Horses of the experimental group received postoperative peritoneal lavage; horses of the control group did not receive peritoneal lavage. The day after surgery, 24 hours after the preoperative dose of gentamicin, a second dose of gentamicin was administered. Three and 15 hours after this second dose of gentamicin, horses of the experimental group received peritoneal lavage. Venous blood was obtained, for determination of concentration of gentamicin, immediately before and at specified intervals during the 24-hour period after the second dose of gentamicin. RESULTS: There were no differences in any of the pharmacokinetic values of gentamicin between horses of the control and experimental groups. CONCLUSIONS: Peritoneal lavage had no effect on pharmacokinetics of gentamicin in healthy horses after abdominal surgery, in which localized nonseptic peritonitis was induced. CLINICAL RELEVANCE: Peritoneal lavage in horses with localized nonseptic peritonitis or for the prevention of intra-abdominal adhesions should not necessitate alteration of the dosage of gentamicin to maintain predictable serum concentrations.

Tension band plating of an olecranon fracture in a bull.

A 1,018-kg (2,240-lb), 6-year-old bull was admitted for evaluation of a left forelimb lameness of 7 days' duration. Radiographic views of the proximal portion of the left forelimb revealed a type-III olecranon fracture that was minimally displaced. Conservative treatment, including stall confinement and administration of anti-inflammatory drugs, was attempted. Subsequent radiographic views, 27 days later, revealed displacement of the fracture with minimal callus formation. Open reduction and internal fixation was performed by placing a 4.5-mm, 10-hole broad dynamic-compression on the caudal surface of the olecranon. Good anatomic reduction was achieved, returning the bull to full weightbearing. Eight months following surgery the owners reported the bull was sound at a walk and able to breed cows.

Cosmetic dehorning in goats.

OBJECTIVE: This article describes a technique using primary closure when dehorning goats, and report the results of 22 cases. STUDY DESIGN: Medical records of goats that had cosmetic dehorning were reviewed. ANIMALS OR SAMPLE POPULATION: Twenty-two goats. METHODS: The medical records of 22 goats, not previously dehorned by other methods, that were cosmetically dehorned between January 1988 and September 1995 were reviewed. Data retrieved from the medical record included age, breed, sex, surgical technique used for dehorning, and any complications that occurred after surgery. All clients were contacted by telephone to determine the course of postoperative healing for each goat. A surgical technique to remove the horns and close the defect primarily was described. RESULTS: The mean age of the goats, all male Nubian or Nubian-Spanish cross, was 6.9 months (range, 2 to 24 months). Horn base diameter ranged from approximately 2 to 4 cm. Mean time from surgery until follow-up was 12.9 months (range, 3 to 57 months). All incisions healed by first intention in 10 to 14 days. Clinical signs of sinusitis were not noted, and owners were pleased with the healing time and cosmetic result obtained. CONCLUSIONS: Primary closure of skin defects after dehorning of goats can be achieved with minimal postoperative care and excellent cosmetic appearance. CLINICAL RELEVANCE: Primary closure after dehorning in mature goats reduces aftercare.

Evaluation of skin bacterial flora before and after aseptic preparation of clipped and nonclipped arthrocentesis sites in horses.

OBJECTIVE: This study evaluates skin bacterial flora before and after aseptic preparation of clipped and nonclipped arthrocentesis sites in horses. STUDY DESIGN: The hair over one midcarpal joint and one distal interphalangeal joint on each horse was clipped. The contralateral joint served as the nonclipped comparison. ANIMALS OR SAMPLE POPULATION: Twelve adult horses. METHODS: A prescrub sample for microbial culture was taken from the dorsal surface of all four joints for each horse. Each site was aseptically prepared with povidone iodine and 70% alcohol, followed by postscrub sampling for microbial culture. Colony forming units (CFUs) were determined for each sample, 24 hours after inoculation of blood agar plates. RESULTS: There was no significant difference (P > .05) in number of postscrub CFUs between clipped and nonclipped skin over the midcarpal or distal interphalangeal joints. Percent bacterial reduction (mean +/- SD%) after aseptic preparation differed significantly (P = .02) between clipped (99.8 +/- .003%) and nonclipped (96.2 +/- .05%) skin at the midcarpal joint, but not at the distal interphalangeal joint (clipped, 98.5 +/- .03% and nonclipped, 97.8 +/- 0.21%). There was a significant difference (P = .009) in number of prescrub CFUs obtained from clipped and nonclipped skin for the midcarpal joint. There was no significant difference in number of prescrub CFUs between clipped and nonclipped skin at the distal interphalangeal joint. Bacteria isolated from both clipped and nonclipped skin sampled postscrub included Bacillus sp, nonhemolytic Staphylococcus sp, and Micrococcus sp. CONCLUSIONS: The presence of hair over the midcarpal and distal interphalangeal joints does not appear to inhibit the ability of antiseptics to effectively reduce bacterial flora to an acceptable level for arthrocentesis. CLINICAL RELEVANCE: Aseptic preparation of the skin over the midcarpal and distal interphalangeal joints can be accomplished without hair removal in horses.

An antibody that binds domain 1 of CD4 inhibits replication of HIV-1, but not HTLV-I, in a CD4-positive/p56lck-negative HTLV-I-transformed cell line.

mAbs that bind to the Ig CDR3-like region in D1 domain of the CD4 molecule can inhibit the HIV-1 life cycle in CD4-positive T cells and lymphoblastoid cell lines at the stage of transcription. This antiviral effect requires the integrity of the cytoplasmic tail of CD4, which acts as a signal transduction region through its association with protein tyrosine kinases such as p56Ick. Here we investigated the role of p56Ick in the cascade of molecular events that control HIV-1 transcription in cells treated with anti-CD4 mAb directed against the Ig CDR3-like region. The Ig CDR3-like region-specific mAb, 13B8-2, blocked HIV-1 production in CD4-positive/p56Ick-negative HTLV-I-producing MT2 cells superinfected by HIV-1Lai, but had no effect on HTLV-I production, although it did inhibit Tax-induced NF-kappa B translocation. These results raise the possibility that an as yet unidentified tyrosine kinase may be capable of associating with CD4 and mediating intracellular signaling.