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Biomedical subjects

K F Bowman

Publications and source records attributed to K F Bowman.

35 records · Page 2Linked to original sources

The isolated perfused porcine skin flap (IPPSF). I. A novel in vitro model for percutaneous absorption and cutaneous toxicology studies.

This article describes the development of a novel in vitro alternative animal model for dermatology and cutaneous toxicology. A single-pedicle, axial-pattern, island-tubed skin flap was created in crossbred Yorkshire weanling pigs in one surgical procedure, then transferred 2 or 6 days later to a computer-controlled temperature-regulated perfusion chamber for 10-to 12-hr studies. Perfusate consisted of Krebs-Ringer bicarbonate buffer (pH 7.4) containing albumin and glucose. Viability was assessed by glucose utilization, lactate production, an absence of significant concentrations of the intracellular enzyme lactate dehydrogenase in the perfusate, and light and electron microscopy. A mean lactate to glucose ratio of 1.6 for flaps harvested 2 days after surgery and 1.8 for flaps taken 6 days after surgery suggested primarily anaerobic glycolysis. This preparation would be a humane alternative animal model for studies in cutaneous toxicology, physiology, oncology, and percutaneous drug absorption and metabolism.

Animals↗

Prediction of pharmacokinetic profiles of ampicillin sodium, gentamicin sulfate, and combination ampicillin sodium-gentamicin sulfate in serum and synovia of healthy horses.

Pharmacokinetics of ampicillin sodium (11 mg/kg), gentamicin sulfate (2.2 mg/kg), and combination ampicillin sodium-gentamicin sulfate were determined for serum and synovia of healthy horses given single-dose IV injection and were not found to be different from those from other reports; however, a prolonged terminal gamma-phase for gentamicin (8,498 +/- 1,842 minutes) in serum of horses was found to exist. Pharmacokinetic interaction between combination ampicillin sodium-gentamicin sulfate was not observed int he serum or synovia. Prediction of ampicillin sodium or gentamicin sulfate concentrations in synovia, based on serum-based pharmacokinetics, cannot be accomplished solely upon analysis of peripheral-compartment pharmacokinetics. However, once equilibrium is achieved between synovia and extracellular fluid in the peripheral compartment, the decrease in drug concentrations in synovia parallels that in serum. Therefore, after 6 hours, synovial concentrations of gentamicin sulfate can be predicted based on peripheral-compartment pharmacokinetics, using an appropriate correction factor. The significance of these findings need to be correlated with clinical conditions so that a pharmacostatistical model for the prediction of synovial concentrations of drug(s) during treatment of horses with septic arthritis can be developed.

Ampicillin↗

Increased gentamicin nephrotoxicity in normal and diseased dogs administered identical serum drug concentration profiles: increased sensitivity in subclinical renal dysfunction.

Attempts to avoid gentamicin-induced nephrotoxicity in the presence of renal dysfunction assume that the nephrotoxicity threshold is unchanged from that of the normal patient. The purpose of the present study was to compare the response of the subclinically diseased kidney to the normal kidney when exposed to identical serum concentrations of gentamicin. This study used exponentially declining infusions based on preinfusion pharmacokinetics to achieve identical serum gentamicin concentration profiles in intact (intact-gentamicin) and subtotally nephrectomized (nephrectomized-gentamicin) beagle dogs. After 10 daily 12-hr infusions, relative nephrotoxicity was compared using serum chemistries and histopathologic analysis in intact- and nephrectomized-control (untreated) dogs. For intact-gentamicin and nephrectomized-gentamicin dogs, respectively, infusion steady-state serum concentrations were 5.3 +/- 0.3 vs. 5.5 +/- 0.5 (microgram/ml) and elimination rates were 0.19 +/- 0.02 vs. 0.20 +/- 0.01(hr-1) (mean +/- S.E.M.). Postinfusion histopath scoring of renal lesions (0-30, with 30 being most severe) were 11 +/- 5 (nephrectomized-gentamicin), 4 +/- 2 (nephrectomized-control), 2 +/- 2 (intact-gentamicin) and 0 +/- 0 (intact-control). Gentamicin-induced renal dysfunction in nephrectomized dogs was characterized further by administering nonindividualized multiple dosage regimens. Toxicity in the subclinical disease state was marked by oliguria and acute renal failure in contrast to the mild polyuria seen in intact animals. These findings support increased sensitivity to gentamicin nephrotoxicity in dogs with mild renal dysfunction secondary to subtotal surgical nephrectomy.

Animals↗

Decreased fractional renal excretion of gentamicin in subtotal nephrectomized dogs.

The purpose of this investigation was to determine the effects of subtotal surgical nephrectomy (three-quarters removal of renal mass) on the renal handling of gentamicin in the dog. Three and one-half months after surgery, dogs were anesthetized and steady-state clearances of gentamicin, creatinine, inulin and p-aminohippurate were determined. Subtotal nephrectomy proportionately decreased creatinine, inulin and p-aminohippurate clearances, but resulted in a significantly (P less than .05) decreased fractional excretion of gentamicin (0.97 +/- 0.24) (mean +/- S.D.) compared to intact dogs (1.22 +/- 0.08). Gentamicin serum protein binding by equilibrium dialysis was approximately 15% in both groups. In vitro canine cortical tissue slices accumulated drug as the slice/medium ratio was greater than one (1.77 +/- 0.47). This study indicates that the renal handling of gentamicin is altered in this disease model. This decreased fractional excretion of gentamicin implies that the quantity of drug excreted by the diseased kidney cannot be precisely predicted on the basis of glomerular filtration rate alone when drug dosage regimens are designed for patients with renal disease.

Absorption↗

Complications during treatment of traumatic disruption of the suspensory apparatus in Thoroughbred horses.

A total of 19 Thoroughbred horses were treated for traumatic disruption of the suspensory apparatus, using either external support of the injured limb, removal of fractured proximal sesamoid bone fragments, metacarpophalangeal arthrodesis, compression screw fixation of the fractured proximal sesamoid bones, application of a cast-brace attached to a transfixation pin inserted through the third metacarpal bone, or combinations thereof. Major complications during the treatment of traumatic disruption of the suspensory apparatus were infection (9 of 19 horses, 47%), large cast sores (10 of 14 treated horses, 71%), laminitis (7 of 19 horses, 37%), and orthopedic implant failure or loosening (4 of 6 treated horses, 67%), which led to euthanasia in 16 of 18 cases with complete follow-up information. Increased pain and lameness signaled the development of such complications. In 7 of 9 cases with infection confirmed by microbiologic culture, the horse had received surgical treatment; in 6 of those 7 cases, the infection involved the surgical site. Postoperative wound infection developed in 4 of 7 cases when the surgery was performed within 18 days of injury. In 3 cases, septic metacarpophalangeal arthritis developed, but it was unrelated to surgical procedures. Implant failure or loosening and infection led to euthanasia in 5 of 6 horses treated by internal fixation to stabilize the metacarpophalangeal joint. Three of 6 attempts to perform metacarpophalangeal arthrodesis by application of a bone plate to the dorsal aspect of the joint resulted in implant failure after 45 to 101 days. Major complications did not develop in 2 horses that were treated successfully.

Animals↗

Complications of cleft palate repair in large animals.

Seven foals, 2 horses, and 2 calves were presented to the George D. Widener Hospital for Large Animals at New Bolton Center and the Large Animal Clinic at Auburn University for surgical repair of cleft palate. All animals had preexisting pneumonia. Initial repair of cleft palate in 6 foals, 2 horses, and 2 calves was performed via mandibular symphysiotomy. Primary repair of cleft soft palate in a foal was attempted through a pharyngotomy incision after fracture of the basal hyoid bone; however, exposure was inadequate and mandibular symphysiotomy had to be done. Dehiscence of a portion of the cleft palate occurred in all cases (10 of 11) that survived the immediate postoperative period. A 2nd repair was attempted in 3 foals; however, dehiscence of the palate recurred. Osteomyelitis of the mandibular symphysis developed in 6 animals; dehiscence of the lower lip occurred in 3 animals. Serious complications after surgery led to euthanasia or death of 5 animals. Of the 6 surviving animals, 4 did not grow normally. All survivors experienced chronic nasal discharge often contaminated with food material. Although mandibular symphysiotomy provided adequate exposure for surgical repair of cleft palate, serious complications have not been overcome.

Animals↗

Cutaneous form of bovine papular stomatitis in man.

A cutaneous form of bovine papular stomatitis (BPS) infection was diagnosed in eight persons at the School of Veterinary Medicine at Auburn University, Auburn, Ala. The initial outbreak occurred in five persons who were involved in the care of a bull that required manual placement of an oral feeding tube. Confirmation of diagnosis was based on clinical findings, cytopathological effects in tissue culture, and isolation of typical paravaccinia virus particles in tissue culture. Transmission studies were performed successfully in three normal calves using tissue culture prepared from human biopsy material. In man, the cutaneous form of BPS infection shows gross lesions similar to the cutaneous form of contagious ecthyma ("orf") or pseudocowpox ("milkers' nodules") infection. Because BPS in cattle occurs most often without evidence of readily observable lesions, unlike contagious ecthyma in sheep or pseudocowpox in cattle, the transmission of BPS to man in the cutaneous form could occur without apparent source. The mild clinical manifestations make the condition relatively minor; however, the occasional case may have more severe lesions.

Adult↗

Transendoscopic Nd:YAG laser surgery for treatment of epiglottal entrapment and dorsal displacement of the soft palate in the horse.

Transendoscopic neodymium:yttrium-aluminum-garnet (Nd:YAG) laser was used to treat 12 standing horses with epiglottic entrapment (EE) or dorsal displacement of the soft palate (DDSP), or both. In four horses, transendoscopic laser staphylectomy was performed. The most common presenting complaints were respiratory stridor, cough, and exercise intolerance. Ten horses with EE healed without epiglottic complications; in one horse, partial adhesion of the aryepiglottic fold to one side of the epiglottis was corrected surgically through a laryngotomy incision. One horse with DDSP had no further signs, one continued to have continual DDSP, and two had induced DDSP. Transendoscopic Nd:YAG laser proved to be a feasible means of correcting EE and selected cases of DDSP.

Animals↗

The isolated perfused equine skin flap. Preparation and metabolic parameters.

A model for the study of equine cutaneous physiology, pharmacology, and toxicology was developed. Four 4 x 12 cm and twenty-one 6 x 12 cm single-pedicle axial pattern skin flaps based on the caudal superficial epigastric artery, and eight 6 x 12 cm flaps based on the saphenous artery and medial saphenous vein, were raised and sutured in a tubed configuration. On day 2, each flap was removed, the artery was cannulated, and the flap was perfused with a modified Krebs-Ringer's albumin-based medium for at least 6 hours. Flap viability was assessed by glucose use, lactate production, and histologic examination at the end of the perfusion period. The 4 x 12 cm flaps had evidence of skin necrosis, but the 6 x 12 cm flaps remained histologically viable. Results were compared to those previously reported from perfusion of porcine skin flaps based on the caudal superficial epigastric artery. While the ratios of glucose use to lactate production were similar, equine flaps used less glucose and produced less lactate per gram of tissue than similar pig flaps. Equine skin flaps perfused by saphenous vessels used more glucose and produced more lactate than flaps perfused by caudal superficial epigastric vessels. These results indicate that conclusions drawn from cutaneous physiology studies should not be extrapolated across species lines and that site-specific skin should be used for cutaneous physiology, pharmacology, and toxicology studies. The identified skin flaps may have applications in equine reconstructive surgery.

Abdomen↗

Leiomyoma of the small colon in a horse.

A leiomyoma of the small colon was discovered incidentally in a 4-year-old Thoroughbred gelding during colic surgery to correct large colon displacement. The mass and 20 cm of small colon were resected, and an end-to-end anastomosis was performed. A postoperative fecal impaction proximal to the anastomosis responded after 5 days to administration of intravenous fluids, analgesics, and stool softeners.

Anastomosis, Surgical↗

Incarceration of the small intestine in the epiploic foramen. Report of 19 cases (1983-1992).

The medical records of 19 horses referred for colic and subsequently found (18 confirmed, 1 suspected) to have small intestinal incarceration through the epiploic foramen were reviewed. These horses were of various ages and breeds; they had clinical signs of colic for an average duration of 13.5 hours before examination. Seventeen horses had nasogastric reflux, and 15 had palpable small intestinal distention. Three horses were killed during surgery because of severe intestinal damage. Of the remaining 16 horses, 13 required intestinal resection and anastomosis. The length of incarcerated small intestine varied from 8 cm to 17.6 m. The ileum was involved in 12 cases. In one horse, the mesoduodenum was disrupted before surgery, causing intra-abdominal bleeding; incarceration of bowel was not found during surgery. The short-term (1 month) survival rate was 74% (14 of 19 cases), and the long-term survival rate was 63% (12 of 19 cases). The follow-up period was 3 months to 45 months (mean 17.2 +/- 7.2 months).

Anastomosis, Surgical↗