Estimating glomerular filtration rate in youth with obesity and type 2 diabetes: the iCARE study equation.

BACKGROUND: The validity of pediatric estimated glomerular filtration rate equations (eGFRs) in early stages of CKD including hyperfiltration is unknown. The purpose of this study was to develop an eGFR equation for adolescents with obesity and type 2 diabetes (T2D). METHODS: eGFRs were developed from iohexol-derived GFRs (iGFRs) in 26 overweight/obese (BMI > 85th percentile) youth and 100 with T2D from the iCARE (Improving renal Complications in Adolescents with T2D through REsearch) cohort. Twenty percent of the cohort was withheld as a validation dataset. Linear regression analyses were used to develop the best formula based on body size, sex, creatinine, urea, ± cystatin C. Comparable validity of commonly used eGFR equations was assessed. RESULTS: Mean age 15.4 + 2.4 years, BMI Z-score 2.5 + 1.2, 61% female, and mean iGFR 129.0 + 27.7 ml/min/ 1.73 m2. The best adjusted eGFR formula (ml/min/1.73 m2) was 50.7 × BSA0.816 × (height (cm)/creatinine)0.405 × 0.8994 if sex = female | 1 otherwise. It resulted in 53.8% of eGFRs within 10% of measured iGFR and 96.2% within 30%. Bland-Altman 95% limits of agreement in the external dataset were - 37.6 to 45.5 ml/min/1.73m2 (bias = 3.96), and the correlation was 0.62. This equation performed better than all previously published creatinine-based eGFRs. cystatin C did not significantly improve results; however, some other cystatin C formulas also performed well. CONCLUSIONS: The iCARE equation provides a more accurate creatinine-based eGFR in obese youth with and without T2D. Further studies are warranted to evaluate within-subject variability and applicability to lower GFRs and other populations.

Comparison of the effect of oxygen supplementation using flow-by or a face mask on the partial pressure of arterial oxygen in sedated dogs.

AIMS To compare the effect of oxygen supplementation using flow-by or a face mask on the partial pressure of arterial oxygen (PaO2) in sedated dogs. METHODS Twenty healthy dogs weighing >15 kg, of mixed sex and breed, were enrolled in a randomised cross-over study. Each dog was sedated with I/M 0.015 mg/kg medetomidine and 0.5 mg/kg methadone. Twenty minutes later dogs were exposed to two 5-minute treatment periods of oxygen supplementation separated by a 15-minute washout period during which dogs were allowed to breathe room air. During the treatment periods, oxygen was delivered at a flow rate of 3 L/minute either through a face mask (face mask oxygenation), or via a tube held 2 cm from the dog's nares (flow-by oxygenation). The order in which the treatments were administered was randomised. Arterial blood was collected for blood gas analysis and rectal temperature measured at four times: prior to commencing treatments, after each treatment, and at the end of the 15 minutes washout period between treatments. RESULTS The mean PaO2 in arterial samples taken from the dogs after face mask oxygen supplementation was 371.3 (SE 13.74) mmHg which was higher than in samples taken after they received flow-by oxygen supplementation (182.2 (SE 6.741) mmHg; p<0.001). The mean PaO2 in samples taken after receiving either form of oxygen supplementation was higher than in samples taken after the dogs had been breathing room air (82.43 (SE 2.143) mmHg; p<0.001). There was no association between sex, age, weight or breed of dogs and blood gas parameters or rectal temperature (p>0.05). CONCLUSIONS Oxygen supplementation delivered using a face mask was more effective at increasing PaO2 than flow-by oxygen supplementation. Flow-by oxygen supplementation at a distance of 2 cm from the nose may be a suitable alternative when the use of a face mask is not tolerated by the patient.

A pilot study comparing the effect of orally administered esomeprazole and omeprazole on gastric fluid pH in horses.

AIMS To compare the efficacy of an enteric coated esomeprazole paste with an enteric coated omeprazole paste to increase gastric pH after oral administration in horses. METHODS Nine adult Standardbred horses were randomly assigned to three groups, each containing three horses, for a study comprising three phases of 10 days, with an 18-day washout period between each phase. In each phase, three horses received either 0.5 mg/kg esomeprazole, 1 mg/kg omeprazole or a placebo, as an oral paste, once daily for 10 days (Days 0-9). Over the course of study all horses received all three treatments. Gastric fluid samples were collected using a gastroscope on Days 1, 3, 5, 8 and 10, with food and water withheld for 16 hours prior to collection of samples. The pH of all samples was measured immediately after collection. RESULTS Mean pH (3.38; SD 1.75) of the gastric fluid samples in the horses that received the placebo was lower than in the horses that received esomeprazole (6.28; SD 1.75) or omeprazole (6.13; SD 1.75) (p<0.001). There was no difference in the mean pH between horses receiving esomeprazole and those receiving omeprazole (p=0.56). CONCLUSIONS AND CLINICAL RELEVANCE Under these study conditions, esomeprazole paste was equally as effective as omeprazole paste in increasing gastric pH in horses. Enteric coated esomeprazole, may be a therapeutic alternative to omeprazole for the prevention of gastric ulcers in horses.

Does First Nations ancestry modify the association between gestational diabetes and subsequent diabetes: a historical prospective cohort study among women in Manitoba, Canada.

BACKGROUND: Over the past 30 years, the prevalence of diabetes has steadily increased among Canadians, and is particularly evident among First Nations (FN) women. The interplay between FN ancestry, gestational diabetes and the development of subsequent diabetes among mothers remains unclear. METHODS: After excluding known pre-existing diabetes, we explored whether FN ancestry may modify the association between gestational diabetes and post-partum diabetes among women in Manitoba (1981-2011) via a historical prospective cohort database study. We analysed administrative data in the Population Health Research Data Repository using Kaplan-Meier survival analysis and Cox proportional hazards regression. RESULTS: Gestational diabetes was diagnosed in 11 906 of 404 736 deliveries (2.9%), 6.7% of FN and 2.2% of non-FN pregnant women (P < 0.0001). Post-partum diabetes during ≤ 30 years follow-up was more than three times higher among FN women than among non-FN women (P < 0.0001). Diabetes developed in 76.0% of FN and 56.2% of non-FN women with gestational diabetes within the follow-up period. The hazard ratio of gestational diabetes for post-partum diabetes was 10.6 among non-FN women and 5.4 among FN women. Other factors associated with a higher risk of diabetes included lower family income among FN and non-FN women and rural/remote residences among FN women. Among non-FN women, urban residence was associated with a higher risk of diabetes. CONCLUSION: Gestational diabetes increases post-partum diabetes in FN and non-FN women. FN women had substantially more gestational diabetes or post-partum diabetes than non-FN women, partially due to socio-economic and environmental barriers. Reductions in gestational diabetes and socio-economic inequalities are required to prevent diabetes in women, particularly in FN population.

Circulating vitamin D levels are associated with the presence and severity of coronary artery disease but not peripheral arterial disease in patients undergoing coronary angiography.

BACKGROUND AND AIMS: To investigate the association between vitamin D levels, angiographic severity of coronary artery disease, arterial stiffness and degree of peripheral arterial disease (PAD) as assessed by ankle brachial index (ABI). METHODS AND RESULTS: 375 patients undergoing coronary angiography from November 2012 to September 2013 were recruited. Serum 25-hydroxyvitamin D (25OHD) levels were measured as were ABI and pulse wave velocity (PWV). Based on the findings of the coronary angiogram, patients were divided into subgroups: Absent, Single, Double and Triple Vessel Disease (as defined by >50% stenosis in each major coronary artery) 0.275 patients not taking vitamin D supplements were included in the analysis. Mean age was 66.0 ± 11.2 (mean ± SD) years. Levels of 25(OH)D were significantly lower in patients with CAD when compared to patients without CAD (57.0 ± 1.73 versus 70.1 ± 2.46 nmol/L; p < 0.01). One way ANOVA revealed triple vessel disease patients had significantly lower 25(OH)D levels when compared to single vessel disease patients (50.6 ± 2.84 nmol/L versus 61.3 ± 3.16 p < 0.01) and trended to be lower when compared to double vessel disease patients (50.6 ± 2.84 versus 59.0 ± 2.99 nmol/L; p = 0.07). Stepwise regression revealed that age, gender (male), hypertension, hyperlipidemia and 25(OH)D were significant predictors of CAD (p < 0.05). Vitamin D was the most significant predictor for CAD (p < 0.001) There was no correlation between 25(OH)D levels, ABI and PWV. CONCLUSION: Among patients presenting for coronary angiography, low serum 25-hydroxyvitamin D levels are associated with the presence and extent of angiographic CAD but not arterial stiffness or PAD.

Gastrojejunostomy as a treatment for gastric outflow disorders in four adult horses.

Four adult horses with histories of moderate abdominal pain and inappetence were diagnosed with delayed gastric emptying and gastric impaction attributed to pyloroduodenal obstruction (three cases) or duodenitis (one case). A stapled side-to-side gastrojejunostomy was performed on all horses. Two horses returned to work and survived ≥3 years. One horse was euthanased 6 months post-surgery due to recurrent abdominal pain, and one was found dead 5 months postsurgery after an unattended foaling.

Effects of topical treatment of cannabidiol extract in a unique manuka factor 5 manuka honey carrier on second intention wound healing on equine distal limb wounds: a preliminary study.

OBJECTIVE: Evaluate the effect of topical 1% cannabidiol on second intention wound healing in distal limb wounds of horses. DESIGN: Experimental. ANIMALS: Six Standardbred horses. METHODS: A total of five 2.5 cm × 2.5 cm full thickness skin wounds were created on the dorsomedial aspect of the metacarpi of 6 horses. Wounds were contaminated with faeces on the day of wound creation. Each wound was then assigned to a treatment group; compounded 1% cannabidiol in unique manuka factor (UMF) 5 manuka honey, UMF 5 manuka honey, UMF 20 manuka honey or saline. Each treatment was applied topically daily for a total of 42 days. Legs were bandaged and bandages were changed, daily, for 13 days postoperatively. Digital photographs of each wound were taken on day 1 then weekly for 6 weeks. Wound size, daily healing rate and total time to healing were recorded and compared statistically. RESULTS: Irrespective of the treatment, wounds did not retract as expected in the first 7 days after wound creation. There was no difference in wound area, daily healing rate, days to complete healing between treatment groups. CONCLUSIONS: This preliminary study failed to demonstrate any difference in wound healing variables between treatment groups in this model of second intention wound healing. This was unexpected due to the established effects of UMF 20 manuka honey on wound healing using the same model. This may be due to systemic effects of cannabidiol and study design. Further research into the use of cannabidiol in equine wounds is warranted.

Encephalomyocarditis virus infection in alpacas.

Encephalomyocarditis virus (EMCV) infection was detected by real-time reverse transcription PCR (qRT-PCR) in four adult alpacas (Vicugna pacos) from two properties on the Far North Coast of New South Wales (NSW) in April and May 2018 and in two adult alpacas from a third property on the Central Coast of NSW in October 2018. Viral RNA was detected in a range of samples, including blood, fresh body organs and mucosal swabs. EMCV was isolated from the blood and body organs of five of these alpacas. These animals displayed a range of clinical signs, including inappetence, colic, recumbency and death. Necropsy findings included multifocal to coalescing areas of myocardial pallor, pulmonary congestion and oedema, hepatic congestion and serosal effusion. Histopathological changes comprised acute, multifocal myocardial degeneration and necrosis, with mild, neutrophilic and lymphocytic inflammation (5/5 hearts) and mild, perivascular neutrophilic meningoencephalitis (1/3 brains). This is the first report of disease due to EMCV in alpacas under farm conditions, and it identifies EMCV infection as a differential diagnosis for acute disease and death in this camelid species. In addition to the samples traditionally preferred for EMCV isolation (fresh heart, brain and spleen), blood samples are also appropriate for EMCV detection by qRT-PCR assay.

Effect of bandaging on second intention healing of wounds of the distal limb in horses.

OBJECTIVE: To evaluate the effect of a non-occlusive dressing incorporated in a 3-layer bandage on second intention healing of wounds of the distal portion of the limb. STUDY DESIGN: Untreated wounds in 33 adult horses used in four studies using the same wound-healing model conducted over 5 years. METHODS: Standardised, full-thickness wounds were made in the skin overlying the dorsomedial aspect of the mid-metacarpus; 17 horses were bandaged with a non-occlusive dressing covered by gauze-coated cotton wool that was compressed with adhesive tape; 16 horses were left unbandaged. Wounds were photographed weekly for 9 weeks and the images were analysed electronically. RESULTS: There were significant effects associated with bandage (P < 0.0001), week (P < 0.001), and bandage by week interaction (P < 0.0001). There was no difference in wound area at the first time-point after wound creation (P = 0.38). After week 1, there was a difference between bandaged and unbandaged wounds in wound area at each measurement until the end of the study. Bandaged wounds showed greater and more prolonged retraction. Unbandaged wounds retracted for 2 weeks before beginning to contract, whereas bandaged wounds continued to retract for 3 weeks. In bandaged wounds excess granulation tissue required regular trimming, but not in unbandaged wounds. There was no difference between groups in the total days to healing or the overall rate of healing. CONCLUSIONS: These results should be treated with caution until validated with contemporaneous, controlled studies. Covering a wound with a non-occlusive dressing in a 3-layer bandage led to greater wound retraction, modulated the rate of wound contraction and promoted excessive granulation tissue. If excessive granulation tissue is excised regularly, bandaging has no effect on total time to healing.

Pilot study to quantify the time to clear dexamethasone from plasma and urine of adult horses following a single nebulisation.

OBJECTIVE: To quantify the time to clear dexamethasone from plasma and urine of horses following a single nebulisation. DESIGN: Experimental using six Standardbred mares. METHODS: Dexamethasone sodium phosphate (0.04 mg/kg) diluted in 0.9% sodium chloride was administered as an aerosol using a Flexineb E2® nebuliser. Blood samples (0, 2, 4, 6, 8, 10, 12, 24, 32, 48, 72 and 96 h) and urine samples (0, 1, 4, 8, 24, 32, 48, 72 and 96 h) were collected for analysis using liquid chromatography mass spectrometry. RESULTS: Maximum plasma concentrations (tmax ) were reached by the earliest detection point (2 h) after nebulisation (0.6-1.8 ng/mL), but was no longer detectable at 48 h. However, in one horse 0.1 ng/mL was found at 96 h after three consecutive readings of 0 ng/mL. The tmax in urine was reached by the earliest collection point (1 h) after nebulisation (3.2-23.8 ng/mL), but was no longer present in urine at 72 h in five horses, while detectable levels (0.1 ng/mL) were still present at 96 h in one horse. CONCLUSIONS: A single dose of 0.04 mg/kg of DSP administered as an aerosol through a FlexinebE2® mask was no longer detectable in blood at 48 h in six horses tested, but one horse returned a reading of 0.1 ng/mL at 96 h after having no detectable levels. Dexamethasone was not detectable in urine at 72 h in five horses but was detectable at a low concentration (0.1 ng/mL) at 96 h in one horse.

Novel Therapeutic Strategy for Pharyngoesophageal Stricture following Total Laryngectomy.

Current therapeutic strategies for pharyngoesophageal stricture, while effective in the short term, are protracted and costly in the longer term. Conceptually, if a stricture can be dilated with minimal tissue injuries, the rate of fibrosis and the resultant stricture recurrence could be reduced. We evaluated a prototype computer-controlled syringe pump device programmed to distend a commercially available balloon dilator at variable rate, asserting incremental lumen distension pressures tailored to the resistive force encountered within the stricture. We completed 17 graded dilatation procedures among 4 total laryngectomy patients. All patients had a short-term response (1 month), with a mean decrement (improvement) in Sydney Swallow Questionnaire score of 448 (total score range, 0-1700; normal <234). The overall procedural tolerability and safety were encouraging; the only complication was the displacement of the voice prosthesis during 1 dilatation. From a technical viewpoint, the main challenge was to maintain the balloon in position during dilatation.

Knockout of beta(1)- and beta(2)-adrenoceptors attenuates pressure overload-induced cardiac hypertrophy and fibrosis.

BACKGROUND AND PURPOSE: The role of beta-adrenoceptors in heart disease remains controversial. Although beta-blockers ameliorate the progression of heart disease, the mechanism remains undefined. We investigated the effect of beta-adrenoceptors on cardiac hypertrophic growth using beta(1)- and beta(2)-adrenoreceptor knockout and wild-type (WT) mice. EXPERIMENTAL APPROACH: Mice were subjected to aortic banding or sham surgery, and their cardiac function was determined by echocardiography and micromanometry. KEY RESULTS: At 4 and 12 weeks after aortic banding, the left ventricle:body mass ratio was increased by 80-87% in wild-type mice, but only by 15% in knockouts, relative to sham-operated groups. Despite the blunted hypertrophic growth, ventricular function in knockouts was maintained. WT mice responded to pressure overload with up-regulation of gene expression of inflammatory cytokines and fibrogenic growth factors, and with severe cardiac fibrosis. All these effects were absent in the knockout animals. CONCLUSION AND IMPLICATIONS: Our findings of a markedly attenuated cardiac hypertrophy and fibrosis following pressure overload in this knockout model emphasize that beta-adrenoceptor signalling plays a central role in cardiac hypertrophy and maladaptation following pressure overload.

Raised plasma soluble P-selectin in peripheral arterial occlusive disease enhances leukocyte adhesion.

Raised levels of soluble P-selectin (sP-selectin) have been reported in the plasma of patients with vascular diseases; however, the functional importance of this ligand remains unclear. In this study we have examined a potential role for plasma sP-selectin in regulating neutrophil adhesion in patients with peripheral arterial occlusive disease (PAOD). Patients with PAOD had significantly higher levels of sP-selectin (mean+/-SD: 73.3+/-13.0 versus 16.7+/-6.4 ng/mL) and enhanced whole blood leukocyte adhesion to platelets under shear. To examine whether the raised sP-selectin levels can directly influence leukocyte adhesion, isolated neutrophils were incubated with plasma from PAOD patients before and after immunodepletion of sP-selectin. Neutrophil adhesion to fibrinogen increased 2-fold following incubation with PAOD plasma, which was abrogated on sP-selectin immunodepletion. We subsequently demonstrated that recombinant sP-selectin dose-dependently (75 to 250 ng/mL) increased leukocyte adhesion to fibrinogen and platelet monolayers. This increase was PSGL-1 and Src kinase-dependent and correlated with an increase in sP-selectin-mediated Mac-1 activation. sP-selectin-stimulated neutrophil adhesion to platelet monolayers was inversely correlated with shear, such that at low shear (50 s(-1)) a 92.7%+/-15.7 increase in adhesion was observed decreasing to 38.5%+/-11.9 at 150 s(-1) and 10.1%+/-7.4 at 300 s(-1). These studies suggest a potentially important role for sP-selectin in modulating neutrophil adhesion in patients with PAOD, particularly at sites of low shear, where it raises the possibility that raised plasma sP-selectin levels may enhance leukocyte recruitment to vascular injury and promote disease progression.

Effect of reducing inspired oxygen concentration on oxygenation parameters during general anaesthesia in horses in lateral or dorsal recumbency.

OBJECTIVE: To compare the effects of two concentrations of oxygen delivered to the anaesthetic breathing circuit on oxygenation in mechanically ventilated horses anaesthetised with isoflurane and positioned in dorsal or lateral recumbency. METHODS: Selected respiratory parameters and blood lactate were measured and oxygenation indices calculated, before and during general anaesthesia, in 24 laterally or dorsally recumbent horses. Horses were randomly assigned to receive 100% or 60% oxygen during anaesthesia. All horses were anaesthetised using the same protocol and intermittent positive pressure ventilation (IPPV) was commenced immediately following anaesthetic induction and endotracheal intubation. Arterial blood gas analysis was performed and oxygenation indices calculated before premedication, immediately after induction, at 10 and 45 min after the commencement of mechanical ventilation, and in recovery. RESULTS: During anaesthesia, the arterial partial pressure of oxygen was adequate in all horses, regardless of position of recumbency or the concentration of oxygen provided. At 10 and 45 min after commencing IPPV, the arterial partial pressure of oxygen was lower in horses in dorsal recumbency compared with those in lateral recumbency, irrespective of the concentration of oxygen supplied. Based on oxygenation indices, pulmonary function during general anaesthesia in horses placed in dorsal recumbency was more compromised than in horses in lateral recumbency, irrespective of the concentration of oxygen provided. CONCLUSION: During general anaesthesia, using oxygen at a concentration of 60% instead of 100% maintains adequate arterial oxygenation in horses in dorsal or lateral recumbency. However, it will not reduce pulmonary function abnormalities induced by anaesthesia and recumbency.

Surgical correction of metacarpophalangeal valgus deformity in an alpaca.

A 1-month-old alpaca cria presented with a 13 degree valgus deformity of the left metacarpophalangeal joint. The angular limb deformity was centered on the distal metacarpal physes. Transphyseal bridging of the physes was recommended. Two 2.7 mm cortical bone screws were placed either side of the distal metacarpal physes and a figure of eight wire was placed medially around the screw heads. The screws extended through the medial metacarpus into the axial cortex of the lateral metacarpus. Seven weeks after surgery the limb was straight and the screws and wire were removed. Transphyseal bridging of the distal metacarpal physes can be effectively used for the treatment of metacarpophalangeal valgus in crias with open physes.

Renal agenesis in an alpaca cria.

A 4-day-old alpaca cria presented for inappetence that responded to symptomatic treatment. The cria re-presented with acute signs of inappetence and azotaemia. The azotaemia persisted despite intravenous fluid therapy. There was no right kidney on ultrasound and there appeared to be perirenal oedema around the left kidney. A diagnosis of right renal agenesis and acute renal failure of the left kidney was made. The cria failed to improve and was euthanased. Necropsy examination confirmed right renal agenesis and agenesis of the right ureter and right renal artery. A section of left kidney submitted for histological examination revealed diffuse, acute, marked tubular degeneration and nephrosis. The cause of the renal failure in the left kidney was not determined.

Treatment of a metallic foreign body in the cranial cervical region of a horse.

Ingestion of foreign bodies is uncommon in horses when compared with indiscriminate grazers such as cattle. This case report describes the diagnosis and treatment of a cervical abscess in a Thoroughbred racehorse thought to be associated with ingestion of wire. Radiographic and ultrasonographic examination provided a diagnosis, and conservative treatment of the lesion with antimicrobials initially allowed the lesion to localise closer to the skin for safer surgical exploration. Intra-operative ultrasonographic imaging facilitated surgical access, removal of the foreign body, and drainage. While surgical treatment is usually necessary to resolve an abscess, initially conservative therapy may help to improve the prognosis by simplifying surgical access and reducing the risk of surgical complications.

Comparison of the effects of topical application of UMF20 and UMF5 manuka honey with a generic multifloral honey on wound healing variables in an uncontaminated surgical equine distal limb wound model.

OBJECTIVE: To compare the effect of application of manuka honey with unique manuka factor (UMF) 5 or 20 with a generic multifloral honey on equine wound healing variables. METHODS: Two full-thickness skin wounds (2.5 × 2.5 cm) were created on the metatarsus of both hindlimbs of eight Standardbred horses. The wounds on each horse were assigned to 1 of 4 treatments: UMF20 (UMF20) and UMF5 (UMF5) manuka honey; generic multifloral honey (GH); and a saline control. Bandages were changed daily for 12 days, after which treatment was stopped and the bandages were removed. Wound area was measured on day 1, then weekly until day 42. Overall wound healing rate (cm2 /day) and time to complete healing were recorded. RESULTS: There was no difference in wound area for any of the treatments on any measurement day except for day 21, where the mean wound area for wounds treated with UMF20 was smaller than the mean wound area for the UMF5-treated wounds (P = 0.031). There was no difference in mean (± SE) overall healing rate (cm2 /day) among the treatment groups. There were differences in mean (± SE) days to complete healing. Wounds treated with UMF20 healed faster than wounds treated with GH (P = 0.02) and control wounds (P = 0.01). CONCLUSIONS: Treatment of wounds with UMF20 reduced overall wound healing time compared with wounds treated with GH and control wounds. However, using this model the difference in the overall time to complete healing was small.