Biomedical subjects

G A Edwards

Publications and source records attributed to G A Edwards.

At least 19 recordsLinked to original sources

PubMed2004

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.

Animals↗

PubMed2003

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.

Animals↗

PubMed2003

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.

Animals↗

PubMed2002

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.

Animals↗

PubMed2001

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.

Animals↗

PubMed2001

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.

Animals↗

PubMed2001

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.

Acid-Base Equilibrium↗

PubMed2001

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.

Administration, Oral↗

PubMed2001

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.

Absorption↗

PubMed2001

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.

Animals↗

PubMed2001

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.

Animals↗

PubMed2000

Systemic availability and lymphatic transport of human growth hormone administered by subcutaneous injection.

Degradation of human growth hormone (hGH) at the injection site has previously been implicated as the basis for its reduced systemic availability following subcutaneous (SC) administration. The goal of these studies was to develop an animal model which would allow mass balance calculations to (i) quantify the loss at the injection site and (ii) determine the role of the lymphatics in the transport of subcutaneously-administered hGH. The animal model utilized a sheep and enabled simultaneous sampling of blood and collection of either peripheral lymph (via the efferent duct of the popliteal lymph node draining the injection site) or central lymph (via the thoracic lymph duct). In non-lymph cannulated sheep, the systemic availability of hGH following SC dosing was 58.4 +/- 9.1% (mean +/- SEM) relative to an intravenous (IV) control. The availability of hGH decreased to approximately 30-40% when either peripheral or central lymph was collected indicating that a proportion of the dose was transported via the lymph. The fraction of the administered dose collected in peripheral lymph was 61.7 +/- 8.5% (mean +/- SEM), whereas only 8.6 +/- 1.3% was collected in central lymph. These results suggested that loss of hGH within the lymphatics contributed significantly to its reduced systemic availability following SC administration. The total recovery (sum of the systemic availability and the cumulative amount recovered in lymph) of hGH was approximately 93% of the dose in the peripherally-cannulated group indicating that loss at the injection site was minimal.

Animals↗

PubMed2000

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.

Animals↗

PubMed2000

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.

Child↗

PubMed1999

Effects of mesh modification on the structure of a mandrel-grown biosynthetic vascular prosthesis.

Mandrel-grown, mesh-reinforced vascular prostheses require adequate tissue coverage of the mesh for effective clinical function, particularly in low blood flow situations. Development of the ovine collagen-based Omniflowtrade mark vascular prosthesis has shown that the extent of this tissue cover is dependent on the interactions of the mandrel and the mesh with the sheep host. In the present study, the effects of chemical changes to the mesh have been examined. These data indicate that certain treatments of the mesh, particularly collagen or heparin, lead to increased tissue coverage while the number of sheep cells present and the ultrastructure of the resulting vessel remain unchanged.

Animals↗

PubMed1999

In vivo evaluation of modified mandrel-grown vascular prostheses.

The Omniflowtrade mark Vascular Prosthesis (OVP) has been manufactured and extensively tested in animal and human trials. It has mechanical and biological qualities superior to synthetic and biological conduits, particularly in low flow conditions. For further development into the smaller diameter coronary prostheses, the inner luminal surface is of paramount importance. In a previous study this inner surface was modified to produce a more uniformly thicker nonundulating surface. In this study the mandrels of these modified OVPs were treated with either collagen or heparin; the OVPs were evaluated for patency, tissue integration and wound healing, and endothelialization using a dog model comparable to that used to evaluate the unmodified OVP. In all instances, each of the modified prostheses were fully patent and had no signs of any deleterious effects caused by these modifications; no thrombus or aneurysms were visible. The tissue response was rapid with excellent new host collagen deposition within the vessel wall and minimal inflammatory and foreign body giant cells. Endothelialization was noted at the earliest explant time point in central regions of the prostheses, albeit that the histological picture at this time point appeared to reflect a complex atypical intimal layer.

Animals↗

PubMed1999

Ureteric tunnel incision in the fetal pig: a model for non-obstructive prenatal vesicoureteric reflux.

The understanding of vesicoureteric reflux (VUR) continues to improve, particularly as the renal tract can now be assessed prenatally. To further study the evolution of fetal renal changes, we studied two neonatal piglets that had undergone midgestation ureteric tunnel ablation. Dilatation of the pelvicalyceal system was seen radiologically and macroscopically in all three kidneys into which VUR had been created. Despite the study being marred by poor fetal survival, the results indicate that the model should be developed further to explore what appears to be an interrelationship between VUR and renal parenchymal changes in utero.

Animals↗

PubMed1999

Can some physical therapy and manual techniques generate potentially osteogenic levels of strain within mammalian bone?

BACKGROUND AND PURPOSE: Although physical therapy techniques are used to alleviate pain and stiffness in joint injuries, whether these methods are capable of affecting bone is unknown. For example, can these techniques potentially influence bone formation or resorption? To begin exploring this possibility, this study investigated the ability of 4 manual techniques to generate levels of compressive strains that presumably can stimulate bone metabolism. SUBJECTS: Six 3,4 metacarpals from three 3-year-old Merino ewes were used. METHODS: A rosette strain gauge was implanted onto the dorsomedial cortex of each ovine 3,4 metacarpal. Four different manual procedures were applied on 2 occasions on each metacarpal in vivo and ex vivo. Mean peak principal compressive strains were calculated for each technique. RESULTS: Levered bending produced greater mean peak compressive strains than almost all other manual procedures tested in vivo or ex vivo. CONCLUSION AND DISCUSSION: Manual levered bending created levels of compressive strain similar in magnitude to those created by mechanical devices used in previous animal experiments to induce new bone formation (osteogenesis). This animal model appears to be suitable for investigating the effects of manually applied procedures on bone and may establish whether manual techniques can stimulate bone formation.

Analysis of Variance↗