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Biomedical subjects

J A Orsini

Publications and source records attributed to J A Orsini.

At least 19 recordsLinked to original sources

Pharmacokinetics of fentanyl delivered transdermally in healthy adult horses--variability among horses and its clinical implications.

The safety and pharmacokinetics of fentanyl, delivered transdermally at a dosage of 60-67 microg/kg, were investigated in six healthy adult horses. Three transdermal fentanyl patches (Duragesic), each containing 10 mg of fentanyl citrate, were applied to the mid-dorsal thorax of each horse and left in place for 72 h. Plasma fentanyl concentrations were periodically measured throughout this period and for 12 h after patch removal. After an initial delay of approximately 2 h, the plasma fentanyl concentration rose rapidly in a fairly linear fashion, reaching a peak at around 12 h; thereafter, it gradually declined in a roughly linear manner over the next 72 h. There was much individual variation, however. The initial delay ranged from 0 to 5.1 h (mean, 1.91+/-2.0 h), Tcmax ranged from 8.5 to 14.5 h (mean, 11.4+/-2.7 h) and Cmax ranged from 0.67 to 5.12 ng/mL (mean, 2.77+/-1.92 ng/mL). In two horses, the plasma fentanyl concentration failed to reach even 1 ng/mL, whereas in the other four horses it was >1 ng/mL for at least 40 h and for at least 72 h in two of these horses. No adverse effects attributable to fentanyl were observed in any of the horses, indicating that this dosage is safe in systemically healthy adult horses. However, it failed to achieve plasma fentanyl concentrations generally considered to be analgesic (>or=1 ng/mL) in about one-third of horses.

Administration, Cutaneous↗

Pharmacokinetics of imipenem-cilastatin following intravenous administration in healthy adult horses.

In two studies, six healthy adult horses were given imipenem-cilastatin by slow intravenous (i.v.) infusion at an imipenem dosage of 10 mg/kg (study 1) and 20 mg/kg (study 2). The same horses were used in each dosage schedule, with a 2-week washout period between studies. In each dosage group, serial blood and synovial fluid samples were collected for 6 h after completion of the infusion. HPLC was used to determine the imipenem concentration in all samples. Imipenem was well tolerated by all horses at both dosages; no adverse effects were noted during the study period or during the 24-hour postinfusion observation period. The pharmacokinetic profiles of imipenem in the plasma and synovial fluid indicate that an imipenem dosage of 10-20 mg/kg by slow i.v. infusion q6h (every 6 h) is appropriate for most susceptible pathogens.

Animals↗

Cefotaxime kinetics in plasma and synovial fluid following intravenous administration in horses.

Cefotaxime powder was diluted with sterile water to a concentration of 100 mg/mL. The volume of solution was adjusted for each experimental horse to provide a total dose of 15, 20, and 25 mg/kg and was administered by infusion through a jugular vein catheter over a 10-min period. All three doses were administered to each of the six experimental horses at three different times. Cefotaxime concentrations in plasma and synovial fluid samples were measured by high-performance liquid chromatography (HPLC). Standard compartmental analysis techniques and the WinSAAM modeling program were used to determine standard pharmacokinetic parameters for cefotaxime. The plasma and synovial fluid data from the five horses administered the 25 mg/kg dose was analyzed. Plasma cefotaxime concentrations appeared to be linearly related to dose infused and declined in parallel, suggesting linear drug kinetics. Moreover, cefotaxime concentrations declined monotonically suggesting that its disposition kinetics could essentially be described by a one-compartment model rather than the fact that sampling occurred after the infusion was discontinued. Maximum concentration of cefotaxime in plasma occurred immediately after cessation of the infusion. Minimum inhibitory concentrations were determined for Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae, common isolates from septic arthritis in horses. Based on our pharmacokinetic data, a regimen of 25 mg/kg administered i.v. every 6 h appears appropriate for susceptible joint infections in adult horses.

Animals↗

Effects of a histamine type 2 receptor antagonist, BMY-26539-01, on equine gastric acid secretion.

A dose-response study was undertaken of the effects of a newly developed histamine type 2 receptor antagonist, BMY-26539-01, on gastric acid secretion in 4 fasted horses. Doses of 0.1 mg/kg, 0.3 mg/kg, 0.5 mg/kg, or placebo were administered in a randomly assigned treatment sequence. Hydrogen ion concentration and pH were variable during baseline measurements in all 4 animals; however, following BMY-26539-01 administration, mean pH increased and hydrogen ion concentration decreased in a dose-related pattern. At the 0.3 mg/kg and 0.5 mg/kg dose levels, pH remained elevated for > 4 h and > 8 h, respectively. No adverse effects were observed. A significant level of 0.01 was used for all statistical methods.

Animals↗

Cecocolic and cecocecal intussusception in horses: 30 cases (1976-1996).

OBJECTIVE: To determine the prognosis in horses with cecocolic or cecocecal intussusception. DESIGN: Retrospective study. ANIMALS: 30 horses with cecocolic intussusception or cecocecal intussusception. PROCEDURE: Information on history, physical examination findings, and laboratory values was summarized from the medical records. Laboratory data included results of hematologic examination, serum biochemical analysis, and peritoneal fluid color, total nucleated cell count, and total protein concentration. A one-year follow-up via the telephone was used to determine long-term survival. RESULTS: Horses ranged from 7 months to 30 years old, but 63% were < or = 3 years. Standardbred horses were significantly overrepresented. Twenty-six horses had acute-to-subacute disease, and 4 had a chronic wasting disease. Cecal intussusceptions were suspected on the basis of finding a mass on abdominal palpation per rectum (14 of 24 horses) and positive ultrasonographic findings (2 of 3 horses). Thirteen horses with colic for > 1 day had scant, soft feces. Six horses died or were euthanatized without undergoing surgery, and 24 were treated surgically. Six of the latter horses were euthanatized during surgery because of peritonitis, rupture of the cecum, and irreducible intussusception. All 4 horses with a chronic disease were euthanatized because of irreversible changes in the cecum. Of the 18 horses allowed to recover from surgery, 15 survived long-term. Surgical treatments were reduction, with or without partial typhlectomy (6 horses), partial typhlectomy through a colotomy and reduction (6), reduction through a colotomy and partial typhlectomy (3), partial typhlectomy for a cecocecal intussusception (1) and an ileocolostomy (2). CLINICAL IMPLICATIONS: Cecal intussusception has a good prognosis with surgical correction without delay. Reduction through colotomy has a high success rate. Bypass by ileocolostomy should be used as a last resort.

Animals↗

Abdominal surgery in foals.

Foals are good candidates for abdominal surgery because their smaller size permits a more complete abdominal exploration and frequently definitive procedures in many cases. The use of rectal examination is replaced with alternative diagnostic modalities such as barium contrast radiography and ultrasonography. With the advancements in these technologies they can distinguish common gastrointestinal lesions and, in most cases, provide sufficient information to guide surgical intervention. The unique aspects of diagnosis and surgical management of gastrointestinal disorders of the foal are discussed.

Abdomen↗

Tissue and serum concentrations of amikacin after intramuscular and intrauterine administration to mares in estrus.

Concentrations of amikacin in endometrial tissue and plasma were studied in mares in estrus after intrauterine infusion of 1.0 or 2.0 g once a day for 3 consecutive d, and after 9.7 or 14.5 mg/kg body weight (BW) had been injected intramuscularly once a day for 3 consecutive d to determine concentrations of amikacin sulfate in plasma and endometrial tissues, and whether parenteral administration provides any advantages over intramuscular infusion. No amikacin was detected in serum at the 1.0 g dose. At the infusion dose of 2.0 g once a day, very low levels of serum amikacin were detected at 1 and 4 h postinfusion on the 1st treatment day. Amikacin was found to penetrate the endometrium after intramuscular injection; however, the levels attained were not as high as those achieved following intrauterine infusion. Based on the tissue and serum concentrations of amikacin, an intrauterine infusion at a dose of 4.4 mg/kg BW/d would appear to be an appropriate therapeutic regimen for the treatment of gram-negative endometritis.

Amikacin↗

Use of tension band wires in horses with fractures of the ulna: 22 cases (1980-1992).

Twenty-two horses with ulnar fractures were treated, using tension band wires alone or tension band wires in combination with pins or cortical bone screws. Age of the horses ranged from 2 weeks to 12 years (median, 4 months), and body weight ranged from 68 to 477 kg (median, 181 kg). Fractures were classified according to the Donecker and Bramlage ulnar fracture classification and included type 1-a (4 horses), type 1-b (4), type-2 (6), type-3 (1), type-4 (3), and type-5 (4), fractures. Tension band wires alone were used in 7 horses. Tension band wires were used in conjunction with unthreaded pins in 10 horses. In 3 horses, 5.5-mm cortical bone screws were inserted longitudinally instead of pins. A combination of a 5.5-mm cortical bone screw and a pin was used in 2 horses. In addition to pins and tension band wires, 4.5-mm cortical bone screws were placed in lag fashion to aid reduction of comminuted or oblique fractures in 7 of the 22 horses. Fractures healed in 18 (82%) horses. Four horses were euthanatized because of complications that included catastrophic failure of fixation during recovery from general anesthesia in 1 foal, septic arthritis and hyperextension of the contralateral metacarpophalangeal joint in 1 foal, and wound infection with partial disruption of repair in 2 horses. Nonfatal complications developed in 6 horses and included incision infection, partial wound dehiscence, carpal contraction, carpus varus of the contralateral forelimb, slight distraction of proximal fragments of the fractures, bent implants, and distal migration of pins. Long-term monitoring was performed on 17 horses.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, General↗

Alar fold resection in horses: 24 cases (1979-1992).

Between 1979 and 1992, the alar folds were resected bilaterally in 22 horses and unilaterally in 2 horses. Abnormal respiratory tract noise and exercise intolerance were the primary complaints prior to surgery. Significantly (P = 0.01) more Standardbreds underwent resection of the alar folds, compared with the number of Standardbreds in the hospital population during the same period. The alar folds palpated abnormally thick in 13 horses and normal in 11 horses. Temporary dilatation of the nares with mattress sutures or clips lessened the respiratory tract noise and improved exercise tolerance in all 8 horses in which the diagnostic test was performed. Manual elevation of the alar folds reduced respiratory noise in the 11 horses evaluated. Long-term follow-up evaluation by telephone was available for 14 horses. All surgical incisions had healed cosmetically. Respiratory tract noise was decreased, and exercise tolerance improved in 10 of 14 (71%) horses. Complete charted racing information was obtained for 16 horses. Fourteen horses started their first race a mean of 118 days (range, 13 to 321 days) after surgery. The mean number of starts after surgery was 51, with 14 of 16 (88%) horses starting more than 6 times after surgery. Of the 16 horses, 8 horses raced at least 3 times before and after surgery; 4 had improved racing performance, 2 had similar performance, and 2 had decreased performance. Five Standardbreds never raced, and 1 Standardbred raced once before surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Musculoskeletal disorders of the neonate.

Musculoskeletal disorders in newborn foals are complex, multifactorial, and associated with prematurity, dysmaturity, and twinning. They include incomplete ossification of cuboidal bones, tendon laxity, congenital angular limb deformities, septic arthritis, osteomyelitis, and septicemia. Other deformities associated with nutrition, large size, and rapid growth include osteochondrosis, physitis, ruptured tendons, acquired flexural deformities, and postnatal angular limb deformities. Optimal management of the complexly interrelated musculoskeletal disorders of the neonate also is discussed.

Animals↗

Loop colostomy for management of rectal tears and small-colon injuries in horses: 10 cases (1976-1989).

Loop colostomy was performed in 10 horses as treatment for grade-III rectal tears (n = 6 horses), small-colon infarction (n = 2 horses), perirectal abscess and stenosis (n = 1 horse), and small-colon stricture (n = 1 horse). In 7 horses, the colostomy was constructed through a single incision low in the left flank, with closure of the incision around the stoma (single-incision technique). In 3 horses, 2 of which had colostomy performed as a standing procedure, the selected segment of small colon was placed from a flank incision into a separate, small incision low in the left flank (double-incision technique). Five horses underwent colostomy reversal (at 18 to 63 days) and 2 of these horses, both with grade-III rectal tears, recovered completely. Of 8 horses that did not survive, 6 died from the primary disease or associated complications. Technical problems associated with colostomy accounted for death of 2 horses. One horse had gastric rupture attributable to suture occlusion of the small intestine after colostomy reversal, and another horse had complications of incisional infection after repair of a peristomal hernia. Small-colon prolapse through the stoma necessitated premature reversal of the colostomy in a horse that was euthanatized because of worsening laminitis. Minor complications of the colostomy procedure were partial stomal dehiscence (n = 4 horses), partial dehiscence of the flank wound after colostomy reversal (n = 2 horses), and small ventral midline hernia after colostomy reversal (n = 1 horse). Loop colostomy may be of benefit to horses with rectal tears, provided it is done soon after the tear occurs.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Vancomycin kinetics in plasma and synovial fluid following intravenous administration in horses.

Vancomycin hydrochloride was infused intravenously (i.v.) over a 30-min period in five horses at doses of 6.6, 11.0 and 15.4 mg/kg. Vancomycin concentration in plasma and synovial fluid samples was measured using a polarization immunoassay. A pharmacokinetic model was developed to accommodate the special features of the present study. The data were described by a two compartment open model with synovial fluid as an additional compartment in exchange with plasma. Minimum inhibitory concentration (MIC) and minimum bacterial concentration (MBC) were measured for Staphylococcus aureus and Enterococcus sp. using isolates from hospital patients. Based on the pharmacokinetic model and MIC/MBC data, a practical therapeutic protocol for vancomycin administration was established at doses of 4.3-7.5 mg/kg given as a 1-h infusion every 8 h.

Animals↗

Use of gastrotomy to relieve esophageal obstruction in a horse.

Esophageal obstruction of 1 week's duration in a gelding was diagnosed by contrast radiography and esophagoscopy. A food bolus was found at the junction of the caudal thoracic portion of the esophagus and the cardia. A gastrotomy was performed through a cranial abdominal incision and a phytobezoar was manually broken down and removed. The gelding was started on complete pellet food and water on the fifth day after surgery. The horse remained clinically normal more than 1 year after surgery.

Animals↗

Evaluation of three techniques to demonstrate retrograde transport of horseradish peroxidase.

Three methods of tracing neural connections by the use of horseradish peroxidase (HRP) were evaluated: (1) endoneurium injection, (2) injection followed by crushing at site of injection, and (3) nerve transection followed by capping of the proximal stump with a silicone cylinder containing HRP. The capping technique resulted in increased uptake and more uniform distribution of HRP in the nerves under study.

Animals↗

Effects of a histamine type-2 receptor antagonist (BMY-25368) on gastric secretion in horses.

The effects of a potent new histamine-2 (H2) receptor antagonist, BMY-25368, were studied on gastric acid secretion in 5 foals from which food was withheld. Doses of 0.02, 0.11, 0.22, and 1.10 mg/kg of body weight were administered IM in a randomly assigned treatment sequence. Following BMY-25368 administration, hydrogen ion concentration was decreased and mean pH was higher than baseline values in a dose-response pattern. At the 0.22 and 1.10 mg/kg doses, the high pH was sustained for greater than 4 hours. The BMY-25368 thus may be useful for treating gastric ulcer disease in horses.

Animals↗