Rigid removable cover for dorsal wound protection and tube fixation in pigs.

OBJECTIVE: To report the design and benefits of a rigid polyethylene cover 'shell' for the protection of dorsal torso wounds and tube fixation in pigs. METHODS: Open C-shaped polyethylene shells were designed to protect wounds and dressings on the dorsum of pigs used in research into negative pressure dressing-assisted wound healing. The shells were designed to resist trauma and contamination, to be comfortable and expansible, and to facilitate tube fixation and management. Strap fixation was optimised during experimentation. Efficacy was assessed by direct observation of dressing and wound protection, tube integrity and by macroscopic and microscopic assessments of wound healing. RESULTS: The shells effectively protected the wounds against blunt and sharp trauma, were simple to remove and reapply, were well tolerated and allowed for growth of the pigs. Circumferential neck straps attached by lateral straps to the shells proved critical. There was no wound infection or inflammation underlying the shells. Porting tubing via mid-dorsal holes in the shells and affixing the tubing just cranial to these holes prevented tube damage and traction, permitted tube management from outside the cages and allowed the pigs to move freely without becoming entangled. CONCLUSION: These shells effectively protected dorsal skin wounds and dressings, prevented tube damage and facilitated tube management in pigs. Similar systems may be useful for other production animals for wound management and for tube management with negative pressure wound healing, drain tubes or the delivery of nutrition, fluids or medications.

Femoral component failure in canine cemented total hip replacement: a report of two cases.

Femoral stem fracture is reported as an uncommon late complication of cemented total hip replacement in two dogs. In each case surgical salvage was achieved by extirpation of the proximal unstable component of the femoral stem, resulting in acceptable limb function. To the authors' knowledge, intramedullary femoral stem failure has not been previously reported after cemented total hip replacement in the dog. Factors believed to have contributed to implant failure in these dogs are discussed and compared with the same complication in humans.

Performance monitoring in hip fracture surgery--how big a database do we really need?

Systems for collecting information about patient care are increasingly common in orthopaedic practice. Databases can allow various comparisons to be made over time. Significant decisions regarding service delivery and clinical practice may be made based on their results. We set out to determine the number of cases needed for comparison of 30-day mortality, inpatient wound infection rates and mean hospital length of stay, with a power of 80% for the demonstration of an effect at a significance level of p<0.05. We analysed 2 years of prospectively collected data on 1050 hip fracture patients admitted to a city teaching hospital. Detection of a 10% difference in 30-day mortality would require 14,065 patients in each arm of any comparison, demonstration of a 50% difference would require 643 patients in each arm; for wound infections, demonstration of a 10% difference in incidence would require 23,921 patients in each arm and 1127 patients for demonstration of a 50% difference; for length of stay, a difference of 10% would require 1479 patients and 6660 patients for a 50% difference. This study demonstrates the importance of considering the population sizes before comparisons are made on the basis of basic hip fracture outcome data. Our data also help illustrate the impact of sample size considerations when interpreting the results of performance monitoring. Many researchers will be used to the fact that rare outcomes such as inpatient mortality or wound infection require large sample sizes before differences can be reliably demonstrated between populations. This study gives actual figures that researchers could use when planning studies. Statistically meaningful analyses will only be possible with major multi-centre collaborations, as will be possible if hospital Trusts participate in the National Hip Fracture Database.

Evaluation of photo-crosslinked fibrinogen as a rapid and strong tissue adhesive.

Tissue adhesives and sealants are commonly used in surgery either as an adjunct to, or replacement for, sutures. Previously, we have shown that fibrinogen can be crosslinked rapidly to give a high-strength bond in the presence of a ruthenium(II) complex, a persulfate and irradiation with visible light, and that the crosslinked fibrinogen is nontoxic to cells in vitro. This approach addresses limitations to current fibrin sealants that typically have relatively slow curing times and low bond strengths. In the present study, we have evaluated the efficacy and safety of this new biological scaffold sealant in various animal models. When placed as solid implants into rats, the crosslinked fibrinogen persisted for at least 8 weeks but was fully resorbed by 18 weeks with minimal inflammatory responses. When used as a tissue adhesive for repair of skin incisions in rats or as an arterial haemostat in pig, the photo-crosslinked fibrinogen sealed tissue or arrested bleeding within 20 s of application. For the skin incisions, the fibrinogen sealant promoted rapid tissue vascularization and cellular infiltration with no adverse foreign body cell generation. New collagen deposition occurred and with time the matrix had remodelled to acquire large mature collagen fiber bundles which were accompanied by maximum regenerated tensile strength. This biomaterial system may find useful applications in surgical procedures where rapid curing and/or high strength tissue sealing is required.

Recurrent rectal prolapse caused by colonic duplication in a dog.

A 9-month-old female Shar Pei cross-bred dog was presented with a history of recurrent rectal prolapse over 7 months. Repeated reduction and anal purse string sutures and subsequent incisional colopexy failed to prevent recurrent rectal prolapse. Digital rectal examination following reduction of the prolapse identified a faeces-filled sac within the ventral wall of the rectum and an orifice in the ventral colonic wall, cranial to the pubic brim. A ventral, communicating tubular colonic duplication was diagnosed by means of a barium enema. Surgical excision of the duplicated colonic tube was performed via a caudal ventral midline laparotomy. At 20 weeks post-operation, there has been no recurrence of rectal prolapse.

Efficacy of combined cyclosporine A and ketoconazole treatment of anal furunculosis.

Cyclosporine A and ketoconazole were used as a combined therapy to treat 19 dogs with anal furunculosis. Complete resolution of all lesions was achieved in three to 10 weeks, but recurrences occurred in seven of the 19 dogs (36.8 per cent), with remission periods extending from one to six months for these dogs. Adverse effects of treatment included excessive hair loss, intermittent lethargy, vomiting and decreased appetite in some dogs, but none of the signs were considered serious. The results of treatment are comparable with, if not better than, the surgical alternatives. There is an approximate 70 per cent cost saving over the use of cyclosporine alone.

Evaluation of closed pericardial patch grafting for management of severe pulmonic stenosis.

Closed pericardial patch-grafting has been advocated for the treatment of severe pulmonic stenosis. In this study pre- and postoperative echocardiography was used to determine if the transvalvular pressure gradient was successfully lowered by this surgery and whether it remained lowered long term. The valvulotomy-ventriculectomy wire was passed using a blunt needle in four dogs (Bresnock technique1) and via a soft catheter in five dogs (Shores and Weirich modification). Eight of nine patients survived the perioperative period. These dogs were assessed up to 40 months following surgery for clinical and echocardiographic changes. Five cases showed significant decrease in peak pulmonic pressure gradient immediately after surgery (decreasing by 50-81%, P < 0.05), and six cases showed significant decrease 2 to 40 months postoperatively (decreasing by 31-80%, P < 0.005) when compared to preoperative values. There was no significant change in pulmonic pressure gradient from immediately postoperatively to 2 to 40 months postoperatively (P < 0.48). Six dogs showed clinical improvement postoperatively, however persistent right ventricular hypertrophy was observed in all cases. One dog died with symptoms of congestive heart failure 16 months postoperatively. Closed pericardial patch grafting can improve clinical signs in symptomatic patients, however the surgery has significant risks, long term prognosis for these patients is guarded and recurrence of clinical signs and development of congestive heart failure is possible. Cardiac changes can be monitored with Doppler flow echocardiography. Patients with extremely elevated preoperative pressure gradients may be expected to have poorer outcomes.

A retrospective study of unilateral arytenoid lateralisation in the treatment of laryngeal paralysis in 100 dogs (1992-2000).

OBJECTIVE: To determine the effectiveness of unilateral arytenoid lateralisation as a surgical treatment for laryngeal paralysis in dogs. DESIGN: The case records of 100 dogs that received a unilateral arytenoid lateralisation for laryngeal paralysis between 1992 and 2000 were reviewed. The results of questionnaires on surgical outcome, formulated for the animal owner and the referring veterinarian, were analysed. Information obtained for dogs under 10 kg and dogs over 10 kg was analysed separately. RESULTS: The Labrador Retriever was the most commonly affected breed. The male:female ratio was 1.56:1 and the average age of presentation was 9.9 years. The most common month in which surgery was performed was October. The majority of owners (87.7%) felt that their dog's quality of life was improved in the 6 months after surgery. Thirty-three percent of dogs revisited the referring clinic with a respiratory problem following unilateral arytenoid lateralisation, and 10.7% of dogs were reported as having a post-surgical complication associated with the procedure. Following surgery, dogs under 10 kg revisited the referring veterinarian with a respiratory complication more often than dogs over 10 kg. Significantly fewer owners of dogs under 10 kg than owners of dogs over 10 kg felt that their dogs quality of life was improved by surgery (55% versus 93%). CONCLUSION: The majority of owners surveyed reported that unilateral arytenoid lateralisation had improved the quality of their dog's life during the first 6 postoperative months. Owner dissatisfaction with the results of surgery and the reported rate of re-presentation (for respiratory disease) may be higher for small (< 10 kg) dogs. A prospective study comparing the results of unilateral arytenoid lateralisation surgery in large and small dogs may be worthwhile in the future.

Perioperative outcomes after three different single extrahepatic portosystemic shunt attenuation techniques in dogs: partial ligation, complete ligation and ameroid constrictor placement.

OBJECTIVE: To compare the perioperative outcomes of single extrahepatic portosystemic shunt occlusion by complete and partial silk ligation and ameroid constrictor placement in dogs. DESIGN: A retrospective analysis of 30 dogs with single congenital extrahepatic shunts. PROCEDURE: Records between 1990 and 2000 were reviewed. Patient age, breed, weight, presenting clinical signs, clinical pathology results, diagnostic imaging results, the surgery procedure performed, implant used, time taken, intra operative complications and perioperative complications were recorded. Mortality rates were calculated. RESULTS: Twenty dogs had a silk ligation procedure, 10 partially occluded and 10 completely. Ten dogs had an ameroid constrictor placement procedure. Ameroid constrictor surgery was significantly shorter in duration than silk ligation. Time for silk ligation was 91.8 +/- 35.2 minutes (median 90.0); time for ameroid constrictor placement was 71.5 +/- 12.0 (median 72.5, P = 0.049). A reduction in intraoperative complications was also noted in the ameroid constrictor surgery group. CONCLUSION: The ameroid constrictor offered a surgical occlusion procedure of single extrahepatic portosystemic shunts in dogs that was clinically as effective as silk ligation in the perioperative period, with a significantly shorter surgery time.

Plastic particle migration during intravenous infusion assisted by a peristaltic finger pump in an animal model.

The contamination of intravenously administered fluid with foreign material has always been of major concern, but the in-vivo impact of silicone embolisation from administration of fluid via a peristaltic finger pump (PFP) has not previously been assessed. To determine whether silicone particles enter the lungs and to review the histological response, 10 rabbits received an IV infusion of 0.9% saline at 10 ml/kg per hour over a 72-h period, via an IVAC 591 PFP. The lungs were analysed for silicone particles with scanning electron microscopy (SEM) and energy-dispersive X-ray analysis (EDXA). These results were compared with a control group of non-infused animals. Silicone particles were found in 8 of 10 animals in the experimental group and in 2 of 9 control animals, indicating that silicone particles are dislodged during pump-assisted IV infusions. The difference between the control and infused animals was statistically significant using Fisher's exact test (P = 0.023). However, silicone plastic particles in control animals suggest that there is also environmental exposure to silicone in addition to those particles that come from a therapeutic source. The additional finding of elemental silicon (which is one of the constituents of silicone plastic) in both infused and control animals in which silicone plastic was not found indicates that not all elemental silicon in animals reflects the presence of silicone plastic. The clinical significance of each of these two findings is yet to be determined.

A conscious dog model for assessing the absorption, enterocyte-based metabolism, and intestinal lymphatic transport of halofantrine.

Postprandial administration of halofantrine (Hf), an important antimalarial, leads to 3- and 12-fold increases in oral bioavailability in humans and beagles, respectively, and corresponding 2.4-fold and 6.8-fold decreases in metabolic conversion to desbutylhalofantrine (Hfm). Factors contributing to the decreased postprandial metabolism of Hf could include inhibition of presystemic CYP3A metabolism by food components and/or recruitment of the intestinal lymphatics as an absorption pathway. Although previous rat studies confirmed Hf base is a substrate for lymphatic transport, it is difficult to extrapolate such data to higher species, as the largely constant bile flow in a rat precludes attainment of representative pre- and postprandial states, and formulations administered to rats are often not relevant to higher species. These limitations have now been addressed by development of a conscious dog model that allows simultaneous study of intestinal lymphatic and nonlymphatic drug absorption and aspects of enterocyte-based drug metabolism. After oral administration of 100 mg Hf base, the mean fasted and postprandial lymphatic transport was 1.3% and 54% of the administered dose, respectively. Comparison of portal and systemic plasma Hfm concentration profiles suggested enterocyte-based conversion of Hf to Hfm; however, the proportion of Hf metabolized to Hfm was similar after fasted or postprandial administration. Hence, it appears that the previously observed decrease in the postprandial metabolism of Hf is largely a consequence of significant postprandial intestinal lymphatic transport (which bypasses first pass hepatic metabolism). This new dog model will facilitate identification of the key factors that impact bioavailability, lymphatic transport, and metabolic profiles of highly lipophilic drugs.

Animal models for the study of intestinal lymphatic drug transport.

Drug transport via the intestinal lymphatic system has been shown to contribute to the absorption of a number of orally administered highly lipophilic drugs. In order to investigate this phenomenon and assist in the development of improved oral formulations, the use of appropriate animal models is required. This paper reviews the use of various animal models for this purpose, and describes in detail the conscious rat and dog models used in our laboratory. The advantages and disadvantages of both small and large animal models are explored, as well as the factors which have been found to influence the outcome of intestinal lymphatic drug transport studies with these models.

Lymphatic transport of proteins after s.c. injection: implications of animal model selection.

Subcutaneous (s.c.) administration continues to be the main route for the delivery of protein drugs due to their poor bioavailability by most non-parenteral routes. While small drug molecules are rapidly and extensively absorbed after s.c. injection, the systemic bioavailability of protein drugs is often incomplete and variable. Given the widespread use of the s.c. route for protein drugs, surprisingly little is known about the factors that govern the rate and extent of protein absorption from the interstitial space and the role of the lymphatic system in the transport of these molecules to the systemic circulation. The few studies that have directly addressed the role of lymphatic transport in protein bioavailability are complicated by the use of methods and models that vary widely. In this review we will evaluate the available literature describing the lymphatic transport of proteins after s.c. injection and more specifically, address the impact of experimental variation (e.g. site of cannulation, animal model, anesthesia) on the interpretation of the data obtained. We will also describe in some detail the sheep model currently in use in our laboratory, which allows both estimation of the extent of uptake of protein drugs into the lymphatics draining the injection site, and quantification of the contribution of lymphatic transport to the absolute bioavailability.

Comparison of the effects of morphine administered by constant-rate intravenous infusion or intermittent intramuscular injection in dogs.

OBJECTIVE: To compare physiologic and analgesic effects of morphine when given by IV constant-rate infusion or by IM injection to dogs undergoing laparotomy and to determine pharmacokinetics of morphine in dogs following IV constant-rate infusion. DESIGN: Prospective randomized controlled trial. ANIMALS: 20 dogs. PROCEDURE: Dogs undergoing laparotomy were treated with morphine beginning at the time of anesthetic induction. Morphine was administered by IV infusion (0.12 mg/kg/h [0.05 mg/lb/h] of body weight) or by IM injection (1 mg/kg [0.45 mg/lb]) at induction and extubation and every 4 hours thereafter. Treatments continued for 24 hours after extubation. RESULTS: Blood gas values did not indicate clinically significant respiratory depression in either group, and degree of analgesia (determined as the University of Melbourne Pain Scale score) and incidence of adverse effects (panting, vomiting, defecation, and dysphoria) were not significantly different between groups. Dogs in both groups had significant decreases in mean heart rate, rectal temperature, and serum sodium and potassium concentrations, compared with preoperative values. Mean +/- SEM total body clearance of morphine was 68 +/- 6 ml/min/kg (31 +/- 3 ml/min/lb). Mean steady-state serum morphine concentration in dogs receiving morphine by constant-rate infusion was 30 +/- 2 ng/ml. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that administration of morphine as a constant-rate IV infusion at a dose of 0.12 mg/kg/h induced effects similar to those obtained with administration at a dose of 1 mg/kg, IM, every 4 hours in dogs undergoing laparotomy. Panting was attributed to an opioid-induced resetting of the hypothalamic temperature set point, rather than respiratory depression.

Phased-Array intracardiac echocardiography to guide radiofrequency ablation in the left atrium and at the pulmonary vein ostium.

INTRODUCTION: We sought to evaluate the utility of a phased-array intracardiac echocardiography (ICE) device to identify left atrial (LA) and pulmonary vein (PV) anatomy; accurately guide radiofrequency ablation (RFA) to the right or left PV ostium and LA appendage (LAA); and evaluate PV blood flow before and after RFA using Doppler parameters. METHODS AND RESULTS: Twelve adult sheep were anesthetized and an Acuson 10-French, 7-MHz ICE transducer introduced via the internal jugular vein into the right atrium. The LA was imaged and PV anatomy and blood flow documented using two-dimensional and pulsed-wave Doppler. Mean LA dimensions were 4.6 +/- 0.4 x 3.5 +/- 0.5 cm; mean single right and left main PV ostium diameters were 1.5 +/- 0.2 and 1.3 +/- 0.3 cm; and mean right and left PV first-order branch diameters were 0.8 +/-0.2 and 0.6 +/- 0.1 cm. Mean PV maximum inflow velocity for the right PV were 0.30 +/- 0.05 m/sec and for the left PV were 0.35 +/- 0.04 m/sec. The PV ostia and LAA could be targeted accurately for RFA using ICE guidance. At pathologic evaluation, the mean distance of the lesion center to the right or left PV-LA junction was 3.0 +/- 2.0 mm. The mean distance of the lesion center to the posterior margin of the LAA was <4 mm in all cases. There was no significant increase in PV maximum inflow velocity or decrease in PV diameter following RFA at the PV ostium. Absence of PV obstruction was confirmed at pathology. CONCLUSION: Phased-array ICE allows detailed assessment of LA and PV anatomy when imaged from the right atrium; accurate guidance of RFA to the PV ostium and LAA; and immediate evaluation of PV patency after RFA.

Diagnosis and management of cor triatriatum dexter in a Pyrenean mountain dog and an Akita Inu.

Cor Triatriatum Dexter is a rare, congenital cardiac defect in which the right atrium is partitioned into two compartments, effectively creating a triatrial heart. The clinical signs exhibited by the patient usually relate to impeded venous return via the caudal vena cava. The two dogs in this report both displayed ascites from a young age and grew poorly. In both cases the diagnosis was made during echocardiographic examination and was confirmed by angiography. Both dogs were successfully treated by resection of the partitioning membrane within the right atrium, using hypothermia and inflow occlusion to achieve a clear surgical field. Both dogs recovered well, their clinical signs resolved and they have grown to normal adult size.

Lymphatic absorption is a significant contributor to the subcutaneous bioavailability of insulin in a sheep model.

PURPOSE: This study was conducted to explore the role of the peripheral lymphatics in insulin absorption following subcutaneous (SC) administration using a sheep model that allows continuous collection of peripheral lymph and simultaneous assessment of systemic bioavailability. METHODS: In a parallel group design, soluble human insulin (0.5 IU/kg) was administered by bolus SC injection into the interdigital space of the hind leg of non-cannulated control sheep, and sheep in which the efferent popliteal lymph duct was cannulated. A separate group received a bolus IV injection (0.15 IU/kg). Blood was sampled from all animals, and lymph was collected continuously over 12 h postdosing. Samples were assayed for insulin by ELISA. RESULTS: The SC bioavailability of insulin in control sheep was 31.5+/-3.2%, which was significantly higher than when the peripheral lymph was continuously collected (18.4+/-1.7%). In the lymph-cannulated animals, 17.3+/-1.0% of the dose was collected in peripheral lymph. CONCLUSIONS: Based on the direct measurement of insulin in regional lymph and on the decrease in the systemic bioavailability when regional lymph was continuously collected, the results demonstrate that lymphatic absorption contributed significantly to the overall insulin bioavailability following SC administration to sheep.

The development of a pig model to study fetal vesico-ureteric reflux.

OBJECTIVE: To develop a surgical protocol to induce vesico-ureteric reflux (VUR) in utero by ablating the ureteric tunnel in a fetal pig model. MATERIALS AND METHODS: Fetal surgery was conducted on nine sows, which were divided into three groups according to changes in the surgical protocol. Sows in groups 2 and 3 received different anaesthetics and antibiotics, and the operating theatre temperature was increased. In all cases, the intramural part of the ureter was unroofed in the fetuses, which were then returned to the uterus. Upon delivery, cystograms were taken in the male piglets, and the urinary tracts removed for anatomical and histological examination. RESULTS: All three sows in group 1 delivered healthy piglets, but the fetuses that had undergone surgery were mummified. In group 2 the animals survived the fetal intervention, as shown by ultrasonography after surgery, but the four sows aborted spontaneously within a week. In group 3, both sows delivered normally developed piglets, three of which had undergone ablation of the ureteric tunnel. VUR was present only in those renal units in which the ureteric tunnel was ablated, and this was associated with hydronephrosis, dilatation of the ureters and thinning of the renal parenchyma on gross pathological examination. CONCLUSIONS: The fetal pig model of VUR not only appears to be feasible, but with similarities in renal anatomy and physiology also seems to be ideal for investigating fetal VUR.

Voiding cystourethrograms and urinary tract infections: how long to wait?

OBJECTIVES: Many authorities recommend an interval of at least 3 to 6 weeks after a urinary tract infection (UTI) before performing a voiding cystourethrogram (VCUG). However, such an interval may reduce the likelihood of completing the procedure. This study was performed to investigate whether the length of the interval between a UTI and the performance of the VCUG influences the presence or severity of reflux, and whether it influences the likelihood of actually having the study performed. DESIGN: We reviewed 352 admissions of children under 10 years old whose discharge diagnoses indicated UTIs. These admissions occurred over a 27-month period between October 1994 and December 1996 at the Children's Hospital of Austin, Texas. We identified 213 patients with confirmed UTIs and no other previously defined urinary tract pathology. These patients were divided into 2 groups according to whether they had a VCUG scheduled to be performed either within 1 week after the diagnosis of a UTI (the early group), or later than 1 week after the diagnosis (the late group). We compared the presence and severity of reflux in the 2 groups as well as the proportion of scheduled VCUGs that were actually performed. RESULTS: Reflux was present in 19% of the patients studied within 1 week after UTI (95% confidence interval [CI]: 12.9-26.4) and in 18% of those studied after 1 week (95% CI: 6. 7-34.5). This difference was not statistically significant (chi(2) =. 034; DF = 1). However there was a substantial difference between the 2 groups with regard to the number of scheduled VCUGs actually performed. Whereas 100% of the scheduled VCUGs in the early group were performed, only 48% (95% CI: 35.9-60.1) of those scheduled in the late group were performed. This difference is statistically significant (chi(2) = 89.6; DF = 1). CONCLUSIONS: In the hospitalized children who underwent VCUGs within a week after diagnosis of UTI, the presence of reflux is not significantly different from those studied later. Furthermore, late scheduling of VCUGs resulted in failure to perform the procedure in more than half of the patients. Some of the patients who were not evaluated would be expected to have vesicoureteral reflux and thus be at risk for chronic renal disease. Therefore, the traditional recommendation to perform the VCUG at 3 to 6 weeks after the diagnosis of UTI should be reconsidered, especially for hospitalized children.