Clinical use of computer-assisted orthopedic surgery in horses.

OBJECTIVE: To describe clinical applications of computer-assisted orthopedic surgery (CAOS) in horses with a navigation system coupled with a cone beam computed tomography unit. STUDY DESIGN: Retrospective clinical case series. ANIMALS: Thirteen adult horses surgically treated with CAOS. METHODS: Medical records were searched for horses that underwent CAOS between 2016 and 2019. Data retrieved included signalment, diagnosis, lameness grade prior to surgery, surgical technique and complications, anesthesia and surgery time, and information pertaining to the perioperative case management and outcome. RESULTS: In 10 cases, surgical implants were placed in the proximal phalanx, third metatarsal bone, ulna, or medial femoral condyle. In one case, navigated transarticular drilling was performed to promote ankylosis of the distal tarsal joints. In another case, an articular fragment of the middle phalanx was removed with the help of CAOS guidance. In the final case, a focal osteolytic lesion of the calcaneal tuber was curetted with the aid of CAOS. In seven cases, a purpose-built frame was used for the surgical procedure. All surgeries were performed successfully and according to the preoperative plan. CONCLUSION: Computer-assisted orthopedic surgery can be an integral part of the clinical case management in equine surgery. To optimize workflow and time-efficiency, the authors recommend designating one team for operative planning and another for the execution of the surgical plan. Specialized equipment, such as the purpose-built frame, will further improve CAOS applications in equine surgery. CLINICAL SIGNIFICANCE: After they have become familiar with the operational principles, equine surgeons can readily apply CAOS for a broad spectrum of indications.

Assessment of symmetric dimethylarginine as a biomarker of renal function in hyperthyroid cats treated with radioiodine.

BACKGROUND: Measurement of serum creatinine (sCr) and urea nitrogen fail to detect decreased renal function in many hyperthyroid cats because of low muscle mass and glomerular hyperfiltration of affected cats. Serum symmetric dimethylarginine (sSDMA) is an earlier and more sensitive renal biomarker than sCr. OBJECTIVE: Evaluate sSDMA as a biomarker of renal function in hyperthyroid cats before (T0) and 1 month after (T1) radioiodine (131 I) treatment. ANIMALS: Forty-seven client-owned hyperthyroid nonazotemic cats were evaluated at T0 and T1. METHODS: A prospective study in which sCr and sSDMA concentrations were determined in 47 hyperthyroid cats at T0 and at T1. Glomerular filtration rate (GFR) was estimated at T0 and T1 in 10 of these 47 cats using plasma exogenous creatinine clearance test. RESULTS: Serum SDMA was elevated (>14 µg/dL) in 6 of 47 cats at T0 and normalized after treatment in 4 of those cats. All cats remained nonazotemic after treatment. In 10 cats in which GFR was measured, correlation between GFR and sSDMA was low and not significant (τb = -0.35, P = .17 at T0 and τb = -.22, P = .41 at T1), whereas correlation between GFR and sCr was moderate and significant (τb = -0.52, P < .05 at T0 and τb = -.53, P = <.05 at T1). CONCLUSIONS AND CLINICAL IMPORTANCE: Careful interpretation of mildly increased sSDMA with normal sCr in hyperthyroid cats is warranted as sSDMA values might normalize after resolution of hyperthyroidism in some cats. In this population of hyperthyroid cats, sSDMA was poorly correlated with GFR.

Long-term follow-up of renal function assessing serum cystatin C in dogs with diabetes mellitus or hyperadrenocorticism.

BACKGROUND: Serum cystatin C (sCysC) is used as biomarker for glomerular filtration rate (GFR). The effects of diabetes mellitus (DM) on renal function in dogs are unclear. Some renal variables have been evaluated in dogs with hyperadrenocorticism (HAC), but not sCysC. OBJECTIVES: The purpose of this study was the validation of a particle-enhanced nephelometric immunoassay (PENIA) for measuring canine sCysC, and to assess renal function in dogs with DM or HAC. METHODS: A PENIA was analytically validated for canine sCysC by determining imprecision and linearity. In a longitudinal 6-month study, renal function of 14 DM dogs was assessed, using serum creatinine, GFR, urinary protein-to-creatinine (UPC) ratio, urinary markers, systolic blood pressure (SBP), and sCysC, and compared to 17 healthy dogs at baseline. Furthermore, sCysC was measured at initial presentation and during a 12-month follow-up in 22 HAC dogs. RESULTS: The sCysC intra- and inter-assay variation coefficients were < 8% and highly linear (r = .997). About 33% and 67% of DM dogs had persistent proteinuria and systemic hypertension, respectively, but there were no significant differences in GFR, UPC, and urinary markers over time, and compared with healthy dogs at initial presentation. Serum CysC decreased significantly (P < .05) over time within the DM group. It did not change significantly over time within the HAC group. CONCLUSIONS: A PENIA measured sCysC linearly and precisely. There were no clinically relevant renal alterations over time in dogs with DM, although persistent proteinuria was observed. In dogs with HAC, sCysC measurement was not useful, although significant GFR changes occurred over time.

ISFM Consensus Guidelines on the Diagnosis and Management of Feline Chronic Kidney Disease.

PRACTICAL RELEVANCE: Chronic kidney disease (CKD) is one of the most commonly diagnosed diseases in older cats. In most cats, CKD is also a progressive disease and can be accompanied by a wide range of clinical and clinicopathological changes. These ISFM Consensus Guidelines have been developed by an independent panel of clinicians and academics to provide practical advice on the diagnosis and management of this complex disease. CLINICAL CHALLENGES: Although CKD is a common clinical problem in cats, the manifestations of disease vary between individuals. Thus there is a need for careful and repeat evaluation of cats with CKD and adjustment of therapy according to individual needs. In addition to addressing problems arising from CKD and improving quality of life (QoL) for the patient, therapy may also target slowing the underlying progression of disease and hence prolonging life. While maintaining QoL is of paramount importance in our patients, this can be challenging when multiple therapies are indicated. In some cases it is necessary to prioritise therapy, given an understanding of what is likely to most benefit the individual patient. EVIDENCE BASE: In preparing these Guidelines, the Panel has carefully reviewed the existing published literature, and has also graded the quality of evidence for different interventions to help to provide practical recommendations on the therapeutic options for feline CKD. This is a field of veterinary medicine that has benefited from some excellent published clinical research and further research findings will undoubtedly modify the recommendations contained in these Guidelines in the future.

Radiographic and Computed Tomographic Configuration of Incomplete Proximal Fractures of the Proximal Phalanx in Horses Not Used for Racing.

OBJECTIVE: To characterize the configuration of incomplete proximal fractures of the proximal phalanx (P1) in horses not used for racing and compare radiographic with computed tomography (CT) findings. STUDY DESIGN: Historical cohort. ANIMALS: Twenty-four horses with incomplete fractures of P1. METHODS: Medical records of horses not used for racing diagnosed with an incomplete proximal fracture of P1 based on clinical and radiographic examination and confirmed by CT between 2008 and 2013 were retrieved. Radiographs and CT studies of these horses were analyzed using a subjective grading system and by measuring variables that characterized fracture configuration. RESULTS: Twenty-four horses were included (20 Warmbloods) with a mean age of 9.5 years and mean body weight of 574 kg. Fourteen forelimbs and 10 hind limbs were affected. Mean duration of lameness was 8.7 weeks. Computed tomography was superior to radiography in both identifying the fracture and determining fracture size and location. On CT, 92% of fractures were located in the mid-sagittal plane. Mean proximodistal length of the fracture was 13 mm. Fractures were frequently not bicortical. Fractures in forelimbs were located significantly more dorsally than fractures in hind limbs. A distinct fracture pattern with 2 subchondral lines running parallel in close proximity to each other was identified in 54% of cases. CONCLUSION: Incomplete proximal fractures of P1 have significant variation in their configurations, especially their dorsopalmar/-plantar location. Computed tomography examination allowed clear identification of the fracture configurations and was superior to radiography.

Simplified methods for estimating glomerular filtration rate in cats and for detection of cats with low or borderline glomerular filtration rate.

OBJECTIVES: Diagnosis of early feline chronic kidney disease (CKD) is challenging. Glomerular filtration rate (GFR) is the best overall indicator of kidney function, but multisample plasma clearance methods to determine GFR are labour intensive, time consuming and stressful for feline patients. This study aimed to develop simplified methods to detect decreased GFR in cats. METHODS: Data from a nine-sample combined plasma exogenous creatinine-iohexol clearance test of 73 cats were used. Limited sampling strategies were developed by comparing all sampling time combinations with the complete nine sampling times set and selecting the best sampling time combinations based on maximum relative error. By regression analysis, the ability of routine blood (serum creatinine, serum urea) and urine (urine specific gravity, urinary protein:creatinine ratio) variables to predict GFR or identify cats with low or borderline GFR was examined. Cut-off clearance marker concentrations to predict low or borderline GFR was determined at three time points after marker injection. All procedures were analysed for three clearance markers (exo-iohexol, creatinine, endo-iohexol). RESULTS: For reliable estimation of GFR, at least three blood samples for clinical purposes and five blood samples for research purposes are required. Regression formulae based on routine variables did not reliably predict GFR, but accurately identified cats with low (sensitivity 96.5-98.2%; specificity 60-91.3%) or borderline (sensitivity 91.1-96%; specificity 76.5-81.8%) GFR. Clearance marker concentrations exceeding given marker cut-off concentrations also identified cats with low or borderline GFR with high sensitivities and specificities. CONCLUSIONS AND RELEVANCE: These simplified methods will facilitate the detection of early kidney dysfunction in cats. Early diagnosis allows timely therapeutic intervention, and future studies must reveal whether this improves the long-term outcome of cats with CKD.

Routine kidney variables, glomerular filtration rate and urinary cystatin C in cats with diabetes mellitus, cats with chronic kidney disease and healthy cats.

OBJECTIVES: Diabetic kidney disease (DKD) is a frequent and serious complication in human diabetic patients, but data are limited in cats. This study was undertaken to assess whether diabetic cats are susceptible to DKD. METHODS: Kidney function was compared between 36 cats with diabetes mellitus (DM), 10 cats with chronic kidney disease (CKD) and 10 age-matched healthy cats by measuring routine kidney variables (serum creatinine [sCreat], serum urea [sUrea], urine specific gravity [USG], urinary protein:creatinine ratio [UPC]), urinary cystatin C:creatinine ratio and glomerular filtration rate (GFR). Urinary cystatin C (uCysC) was measured with a human particle-enhanced nephelometric immunoassay, validated to measure feline cystatin C, in all but two diabetic cats. GFR was evaluated by exo-iohexol clearance in 17 diabetic cats, all cats with CKD and all healthy cats. RESULTS: Diabetic cats had significantly (mean ± SD) lower sCreat (123 ± 38 vs 243 ± 80 µmol/l), sUrea (11 ± 3 vs 18 ± 7 mmol/l) and urinary cystatin C:creatinine ratio (6 ± 31 vs 173 ± 242 mg/mol), and a significantly higher USG (1.033 ± 0.012 vs 1.018 ± 0.006) and GFR (2.0 ± 0.7 vs 0.8 ± 0.3 ml/min/kg) compared with cats with CKD. Compared with healthy cats, diabetic cats only had significantly lower USG (1.033 ± 0.012 vs 1.046 ± 0.008). Proteinuria (UPC >0.4) was present in 39% of diabetic cats, in 30% of cats with CKD and in none of the healthy cats. However, the UPC did not differ statistically between the three groups. CONCLUSIONS AND RELEVANCE: Based on evaluation of routine kidney variables, GFR and uCysC as a tubular marker at a single time point, a major impact of feline DM on kidney function could not be demonstrated.

Routine plasma biochemistry analytes in clinically healthy cats: within-day variations and effects of a standard meal.

Limited information is available on pre-analytical variations in plasma analytes in cats. The objectives of this study were to assess the effects of the time of sampling and a standard meal on plasma analytes in healthy cats. Eight healthy, adult, fasted cats underwent blood sampling every 2 h from 8 am to 8 pm twice at a 12 day interval. On the days of sampling, four cats were kept fasted and the others were fed just after the first sample, in a crossover design. Plasma glucose, urea, creatinine, sodium, potassium, chloride, CO2, calcium, phosphate, proteins, albumin, cholesterol and triglycerides, alanine aminotransferase and alkaline phosphatase were assayed on each sample. Effects of time of sampling and meal on plasma biochemistry results were tested using a general linear model. Diurnal variations in tested plasma analytes in fasted cats were negligible except for urea and creatinine, which gave noticeably higher plasma concentrations in the afternoon than in the morning. Observed postprandial variations were of some importance for phosphate and creatinine and of indisputable clinical relevance for CO2 and urea.

Influence of the observer's level of experience on systolic and diastolic arterial blood pressure measurements using Doppler ultrasonography in healthy conscious cats.

The objective of this study was to determine the influence of the observer's level of experience on within- and between-day variability, and the percentage of successful systolic (SAP) and diastolic arterial blood pressure (DAP) measurements obtained by Doppler ultrasonography (DU) in awake cats. For this purpose, six healthy conscious cats were used and four observers with different levels of training performed 144 SAP and DAP measurements on 4 days using DU. Measurements were recorded five consecutive times, and mean values were used for statistical analysis. Only the two most skilled observers - a PhD student in cardiology and a Dipl ECVIM-CA (cardiology) - had within- and between-day coefficients of variation (CVs) for SAP ⩽16% (13-16%). Conversely, the two less experienced observers - a fifth-year student and an assistant - had high between-day CVs (61% and 73%). For DAP, only the most experienced observer (Dipl ECVIM-CA) succeeded in 100% of the attempts, with within- and between-day CVs of 11% and 4%, respectively. Conversely, DAP could not be measured by the other three observers in 8%, 19% and 56% of attempts (from the highest to the lowest level of experience); therefore, the corresponding CV values could not be calculated. In conclusion, SAP may be assessed using DU in healthy awake cats with good repeatability and reproducibility by a well-trained observer. Measurement of DAP is more difficult than of SAP, and needs a longer training period, which represents one of the limitations of DU in cats.

Feline CKD: Pathophysiology and risk factors--what do we know?

PRACTICAL RELEVANCE: Chronic kidney disease (CKD) is one of the most frequently encountered disorders in cats, having increased in prevalence in recent decades. Although the underlying cause is rarely identified, the common final outcome of feline CKD is tubulointerstitial fibrosis. Knowledge of CKD pathophysiology is necessary for optimal individualised patient management, especially with regard to diagnosis and treatment of extrarenal complications. PATIENT GROUP: CKD is most common in senior and geriatric cats, but should be considered in any feline patient with ureterolithiasis, hyperthyroidism, retrovirus infection, systemic hypertension, cardiovascular disease or urinary tract infection. EVIDENCE BASE: Most of our knowledge of the pathogenesis of CKD is extrapolated from human nephrology and experimental animal studies. There is, therefore, a need for further studies in cats. The prevalence of clinical signs in feline CKD is well documented. Several concurrent diseases associated with CKD have also been reported in cats, especially in the geriatric population, but there is no or only limited published evidence demonstrating a cause-and-effect relationship between most of these conditions and CKD. Studies performed over the past 15 years have nevertheless allowed identification of major risk factors (proteinuria, plasma phosphate and plasma creatinine) influencing the progression of feline CKD. CLINICAL CHALLENGES: Clinical signs occur in the late stages of renal disease, so populations at higher risk of CKD should be screened routinely. CKD-associated complications (systemic hypertension, secondary renal hyperparathyroidism, hypokalaemia, anaemia, metabolic acidosis) must not be overlooked as they may affect the progression of disease. Disease progression is itself unpredictable and renal function may remain stable for extended periods. Most cats with early CKD do not progress to end-stage CKD before they die. AUDIENCE: General practitioners play a major role in screening feline patients at risk of development or progression of CKD.

Renal function and morphology in aged Beagle dogs before and after hydrocortisone administration.

Objectives of this study were to evaluate glomerular filtration rate (GFR), renal structural changes and proteinuria in aged Beagle dogs before and after hydrocortisone (HC) administration. Eleven Beagle dogs ≥10 years old were treated with either hydrocortisone (HC group, n = 6) or placebo (control group, n = 5). Urinary markers, GFR and kidney biopsies were evaluated before (T0), during (T16 wks) and after discontinuing HC administration (T24 wks). Results indicate that HC administration causes a significant increase in GFR. At all time points except T16 wks, proteinuria was higher in the control group than in the HC group, and there was no significant difference in urinary markers between groups. At T16 wks, proteinuria, urinary albumin-to-creatinine (c) ratio, immunoglobulin G/c and retinol-binding protein/c were higher compared to baseline in the HC group. At T0, rare to mild renal lesions were detected in all HC dogs and rare to moderate changes in all control dogs. Glomerulosclerosis progressed in both groups until T24 wks. Tubular atrophy was detected in three HC dogs at T16 wks and T24 wks, but also in five control dogs throughout the study. At every time point, five HC dogs and all control dogs had rare to moderate interstitial inflammation. Rare to mild interstitial fibrosis was found in up to three HC dogs at T16 wks and T24 wks, and severe fibrosis in one HC dog at T24 wks. Up to four control dogs had rare to mild fibrosis at all time points. These findings indicate that clinically healthy, aged Beagle dogs may have considerable renal lesions and proteinuria, which could have implications for experimental or toxicological studies. Additional research is needed to elucidate glucocorticoid effects on renal structure, but functional changes such as hyperfiltration and proteinuria warrant attention to kidney function of canine patients with Cushing's syndrome or receiving exogenous glucocorticoids.

A laparoscopic-sutured gastropexy technique in dogs: mechanical and functional evaluation.

OBJECTIVE: To describe a laparoscopic-sutured gastropexy technique in dogs and evaluate the tensile strength of the adhesion and effects on gastric function. STUDY DESIGN: Experimental study. ANIMALS: Female beagle dogs (n=7). METHODS: A laparoscopic-sutured gastropexy technique was evaluated by ex vivo tensile distraction tests 10 weeks after surgery. The effect of the adhesion on gastric emptying, mucosal permeability, and systemic inflammation were evaluated by monitoring the C-reactive protein (CRP) and sucrose permeability, and by radiographic evaluation of gastric emptying 2 weeks before and 10 weeks after surgery. RESULTS: Mean (+/-SD) tensile force to disrupt adhesions was 51.1+/-16.4 N. There was no significant postoperative increase in CRP concentration or change in sucrose permeability. The area under the curve representing the postprandial decrease in gastric radiographic area increased by 11% after gastropexy. CONCLUSIONS: This laparoscopic gastropexy technique had appropriate mechanical and functional characteristics with limited morbidity. CLINICAL RELEVANCE: This laparoscopic-sutured gastropexy provides adhesion strength comparable with other gastropexy techniques tested at 10 weeks postoperatively. Only minor changes in gastric emptying were observed 10 weeks after surgery.

Comparison of plasma clearance of exogenous creatinine, exo-iohexol, and endo-iohexol over a range of glomerular filtration rates expected in cats.

The study investigated plasma clearance of exogenous creatinine (PECCT), exo-iohexol (PexICT) and endo-iohexol (PenICT) in six healthy cats, four cats with chronic kidney disease (CKD) and six hyperthyroid (HT) cats to assess potential differences in glomerular filtration rate (GFR) measurement over a wide range of GFR values. The PECCT, PexICT and PenICT were performed in a combined protocol. There was a significant difference between PexICT and PenICT and PECCT in healthy cats. Differences between clearance techniques are suggested to be correlated to range in GFRs and should be taken into account when GFR is measured.

Chronic lymphatico-venous bypass: surgical technique and aftercare in a porcine model.

We describe a chronic model of lymphatico-venous bypass in pigs with emphasis to surgical considerations, major per- and postoperative complications. A catheter (silicone or heparin coated polyurethane) was inserted in the thoracic duct of nine pigs via a right intercostal thoracotomy. A second catheter was surgically inserted in the jugular vein and the bypass was secured on the back of the animals. Pigs were monitored for capnography, end-tidal carbon dioxide, systolic, diastolic and mean blood pressure, heart rate, and rectal temperature. Apnea was recorded in every pig in the recovery period leading to one death. During the postoperative period, ventricular tachycardia in 2/9 pigs and hypothermia in 5/9 pigs were recorded. Bypass was effective in 5/9 pigs. Clotting occurred only with silicone catheters (1/2) but not with heparin-coated catheters. In the heparin-coated catheters group, bypass was patent up to 15 days with no major complication recorded. Sampling of lymph was allowed from 2 to 15 days. The immediate postoperative period is critical and should be carefully monitored. Although complications were present, the surgical technique was efficient. Chronic catheterization of thoracic duct is useful in biomedical research in the fields of intensive care, gastro-enterology, pharmacokinetic and hematology studies.

Comparison of a new device for blood sampling in cats with a vacuum tube collection system - plasma biochemistry, haematology and practical usage assessment.

Using paediatric devices to collect venous blood from a cephalic vein in cats offers numerous practical advantages over traditional jugular venepuncture and vacuum closed systems: minimal restraint is required; there is minimal risk of serious injury to the cat; the discomfort associated with venepuncture is reduced by the use of small diameter (25 gauge) needles; very small volumes (200 microl) of blood are extracted; and the risk of vein collapse or haematoma is low. The aim of this study was to compare the haematological and plasma chemistry results obtained from six healthy cats using the two sampling techniques. Five plasma biochemical analytes were measured and a complete haematological examination was performed on each specimen. No clinically relevant difference between the two blood sampling techniques was observed for any variable, indicating that paediatric devices provide a useful alternative to vacuum tubes for venous blood collection in the cat.

Longitudinal analysis of gene expression in porcine skeletal muscle after post-injection local injury.

PURPOSE: The purpose of this study is to describe the time course of gene expression in a skeletal muscle local injury induced by an intramuscular (IM) injection, and to compare the dynamics of gene expression with pathological events. MATERIALS AND METHODS: Ten piglets received 4 IM injections of propylene glycol in the longissimus dorsi muscles 6 h, 2, 7, and 21 days before euthanasia, where control and injected muscle sites were sampled for RNA isolation and microscopic examination. The hybridization of nylon cDNA microarrays was carried out with radioactive probes obtained from the muscle RNA. RESULTS: 153 genes were found under- or over-expressed at least once among the investigated time-conditions. The eight most discriminant genes were also identified: Two genes (GTP-binding protein RAD and Ankyrin repeat domain protein) were over-expressed at 6 h and six genes between 2 and 21 days (Osteonectin, Fibronectin, Matrix metalloproteinase-2, Collagen alpha 1(I) chain, Collagen alpha 2(I) chain, and Thymosin beta-4). Necrosis, inflammation and regeneration were observed through both the dynamics of gene expression profiles and through the microscopic examinations. CONCLUSION: Our data demonstrate that several pathways are involved in post-injection muscle injury, and that necrosis, inflammation and regeneration are not sequential but occur in parallel.

Human and rodent bone marrow mesenchymal stem cells that express primitive stem cell markers can be directly enriched by using the CD49a molecule.

Bone marrow (BM) from human and rodent species contains a population of multipotential cells referred to as mesenchymal stem cells (MSCs). Currently, MSCs are isolated indirectly by using a culture step and then the generation of fibroblast colony-forming units (CFU-fs). Unprocessed or native BM MSCs have not yet been fully characterised. We have previously developed a direct enrichment method for the isolation of MSCs from human BM by using the CD49a protein (alpha1-integrin subunit). As the CD49a gene is highly conserved in mammals, we have evaluated whether this direct enrichment can be employed for BM cells from rodent strains (rat and mouse). We have also studied the native phenotype by using both immunodetection and immunomagnetic methods and have compared MSCs from mouse, rat and human BM. As is the case for human BM, we have demonstrated that all rodent multipotential CFU-fs are contained within the CD49a-positive cell population. However, in the mouse, the number of CFU-fs is strain-dependent. Interestingly, all rat and mouse Sca-1-positive cells are concentrated within the CD49a-positive fraction and also contain all CFU-fs. In human, the colonies have been detected in the CD49a/CD133 double-positive population. Thus, the CD49a protein is a conserved marker that permits the direct enrichment of BM MSCs from various mammalian species; these cells have been phenotyped as true BM stem cells.

Dendritic cell recruitment in lesions of human and experimental pulmonary hypertension.

In the present study, the hypothesis that dendritic cells (DCs), key players in immunity and tolerance, might be involved in the immunopathology of idiopathic pulmonary arterial hypertension (IPAH) was tested. The phenotype and localisation of DCs were characterised by immunohistochemistry and double-labelling immunofluorescence in lung samples from controls, human IPAH patients and an experimental pulmonary hypertension model (monocrotaline-exposed rats). As compared with controls, morphometric analysis demonstrated increased numbers of dendritic cell-specific intercellular adhesion molecule-grabbing nonintegrin (DC-SIGN)-positive cells in muscular pulmonary arteries in IPAH and OX-62-positive DCs in monocrotaline-induced pulmonary hypertension. In human samples, the mean+/-SEM number of DC-SIGN-positive cells.artery(-1) of 100-300 microm diameter was 1.4+/-0.4 in controls versus 26.4+/-2.7 in IPAH. In rats, the number of OX-62-positive cells.artery(-1) of 50-150 microm diameter was 0.5+/-0.2 in controls, and 0.7+/-0.5, 3.1+/-0.5 and 8.4+/-0.6 at day 7, 14 and 28 after monocrotaline exposure, respectively. Human complex lesions of muscular pulmonary arteries showed transmural DC infiltration. Phenotyping revealed an immature DC profile in human and experimental pulmonary hypertension. The results support the concept that immature dendritic cells accumulate in remodelled pulmonary vessels and hence could be involved in the immunopathology of pulmonary hypertension.

Disposition of plasma creatinine in non-azotaemic and moderately azotaemic cats.

The objectives of this study were to compare assay methods for plasma creatinine (Pl-creat) in cats and to describe the disposition of creatinine and iohexol in 12 healthy and moderately azotaemic cats. Exogenous creatinine and iohexol were injected simultaneously by intravenous bolus, and repeated blood samples were taken to determine the pharmacokinetic parameters of each marker. Pl-creat was assayed by high-performance liquid chromatography (HPLC), Jaffé and enzymatic methods. The enzymatic method was shown to be more reliable than the Jaffé method. Two stereoisomers, exo- and endo-iohexol were identified. The plasma clearance of creatinine (2.3+/-0.66 ml/min/kg) was significantly higher (P<0.001) than that of exo-iohexol (1.7+/-0.40 ml/min/kg). The volume of distribution (447+/-97 ml/kg) and elimination half-life (181+/-77 min) of creatinine were also higher (P<0.001) than those of exo- and endo-iohexol. The estimated daily endogenous production of creatinine was 65+/-23 mg/kg. None of the pharmacokinetic parameters was changed by the azotaemic status of the animals.