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.

Physiological Parameter Response to Variation of Mental Workload.

OBJECTIVE: To examine the relationship between experienced mental workload and physiological response by noninvasive monitoring of physiological parameters. BACKGROUND: Previous studies have examined how individual physiological measures respond to changes in mental demand and subjective reports of workload. This study explores the response of multiple physiological parameters and quantifies their added value when estimating the level of demand. METHOD: The study presented was conducted in laboratory conditions and required participants to perform a visual-motor task that imposed varying levels of demand. The data collected consisted of physiological measurements (heart interbeat intervals, breathing rate, pupil diameter, facial thermography), subjective ratings of workload (Instantaneous Self-Assessment Workload Scale [ISA] and NASA-Task Load Index), and the performance. RESULTS: Facial thermography and pupil diameter were demonstrated to be good candidates for noninvasive workload measurements: For seven out of 10 participants, pupil diameter showed a strong correlation ( R values between .61 and .79 at a significance value of .01) with mean ISA normalized values. Facial thermography measures added on average 47.7% to the amount of variability in task performance explained by a regression model. As with the ISA ratings, the relationship between the physiological measures and performance showed strong interparticipant differences, with some individuals demonstrating a much stronger relationship between workload and performance measures than others. CONCLUSION: The results presented in this paper demonstrate that physiological and pupil diameter can be used for noninvasive real-time measurement of workload. APPLICATION: The methods presented in this article, with current technological capabilities, are better suited for workplaces where the person is seated, offering the possibility of being applied to pilots and air traffic controllers.

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.

Long-term safety of dietary salt: A 5-year ProspEctive rAndomized bliNded and controlled stUdy in healThy aged cats (PEANUT study).

BACKGROUND: High-salt diets promote urine dilution and decrease urolithiasis risk. OBJECTIVE: Prospectively evaluate the safety of chronic high dietary salt intake (randomized controlled trial). ANIMALS: Twenty research colony neutered, healthy aged cats (11.5 years [10.0-11.6], median [interquartile range]). METHODS: Healthy cats were randomized to control or high-salt dry diets (sodium: 1.02 ± 0.16 [mean, SD] and 3.26 ± 0.30 g/Mcal metabolizable energy [ME], respectively; chloride: 2.26 ± 0.33 and 5.71 ± 0.28 g/Mcal ME, respectively), fed for up to 60 months. Assessments included CBC, plasma biochemistry, urinalysis, glomerular filtration rate (GFR), blood pressure, renal and cardiac (conventional Doppler and 2-dimensional color tissue Doppler) imaging, annually. Cats that died or were euthanized underwent necropsy. Diet effects over time were evaluated with linear mixed models. RESULTS: Follow-up duration (median [Interquartile range]) was similar between the control (38.7 months [28.6-48.2]) and high-salt group (51.4 months [45.7-59.0]). Diet had no significant effect on changes in GFR, blood pressure, plasma creatinine concentration, end-diastolic left ventricular (LV) wall thicknesses, LV internal diameters, LV systolic function, left atrial size, or systolic and diastolic Doppler variables. One control cat developed hypertension. One high-salt group cat developed persistent azotemia. Serial plasma biochemistry and urine specific gravity suggested early chronic kidney disease in 4 nonazotemic cats (2 per group), consistent with necropsy findings. CONCLUSIONS AND CLINICAL IMPORTANCE: In healthy aged cats, a commercial veterinary diet containing 3.26 ± 0.30 g/Mcal ME sodium was safe with regard to renal and cardiac function for up to 5 years.

Pharmacokinetic/pharmacodynamic modeling for the determination of a cimicoxib dosing regimen in the dog.

BACKGROUND: Cimicoxib is a new coxib anti-inflammatory drug for use in the dog. To determine a preclinical dosage regimen for cimicoxib in dog, a reversible model of kaolin-induced paw inflammation was used. Dosage regimens were established using pharmacokinetic/pharmacodynamic (PK/PD) modeling approach (indirect response model). RESULTS: Analgesic, anti-inflammatory and antipyretic endpoints investigated with the inflammation model established the efficacy of cimicoxib at a dose of 2 mg/kg administered orally (single dose) in 12 beagle dogs.For both the oral and IV route of administration two groups of dogs to be identified namely Poor Metabolizers (PM) and Extensive Metabolizers (EM).The terminal half-life after oral administration was 8.0 ± 0.6 h for the PM and 4.6 ± 2.6 h for the EM groups, with the corresponding values after the IV route being 5.6 ± 1.7 h and 2.7 ± 0.9 h (mean ± SD).The main pharmacodynamic parameters (potency, efficacy, and sensitivity) were estimated for four endpoints (body temperature, creeping speed, ground vertical reaction force and clinical lameness score). The plasma concentration corresponding to half the maximum of the indirect effect were 239 µg/L for creeping speed, 284 µg/L for the lameness score, 161 µg/L for the ground reaction vertical force and 193 µg/L for the body temperature.To document possible polymorphism of the cimicoxib disposition in the target dog population, cimicoxib was administered by the intravenous route to 40 dogs (four different sized breeds). The cimicoxib half-lives in these 40 dogs were of same order of the magnitude as those of the EM beagle dogs. Thus pharmacokinetic and pharmacodynamic parameters obtained from the EM beagle dogs were selected to simulate the dose-effect relationship of cimicoxib after an oral administration allowing a dosage regimen to be selected for confirmation by a clinical trial. CONCLUSIONS: Cimicoxib was an efficacious anti-inflammatory, antipyretic and analgesic drug and a dosage regimen of 2 mg/kg daily was determined for confirmatory clinical trials.

The association between resting and mild-to-moderate exercise pulmonary artery pressure.

The mean pulmonary artery pressure (P(pa)) achieved on mild-to-moderate exercise is age related and its haemodynamic correlates remain to be documented in patients free of pulmonary hypertension (PH). Our retrospective study involved patients free of PH investigated in our centre for possible pulmonary vascular disease between January 1, 2007 and October 31, 2009 who underwent right heart catheterisation at rest and during supine exercise up to 60 W. The 38 out of 99 patients aged <50 yrs were included and a P(pa) of 30 mmHg was considered the upper limit of normal on exercise. The 24 subjects who developed P(pa)>30 mmHg on exercise had higher resting P(pa) (19±3 versus 15±4 mmHg) and indexed pulmonary vascular resistance (PVRi; 3.4±1.5 versus 2.2±1.1 WU·m(2); p<0.05) than the remaining 14 subjects. Resting P(pa) >15 mmHg predicted exercise P(pa) >30 mmHg with 88% sensitivity and 57% specificity. The eight patients with resting P(pa) 22-24 mmHg all had exercise P(pa) >30 mmHg. In subjects aged <50 yrs investigated for possible pulmonary vascular disease and free of PH, patients with mild-to-moderate exercise P(pa) >30 mmHg had higher resting PVRi and higher resting P(pa), although there was no resting P(pa) threshold value that could predict normal response on mild-to-moderate exercise. The clinical relevance of such findings deserves further long-term follow-up studies.

Function of the serotonin 5-hydroxytryptamine 2B receptor in pulmonary hypertension.

Primary pulmonary hypertension is a progressive and often fatal disorder in humans that results from an increase in pulmonary blood pressure associated with abnormal vascular proliferation. Dexfenfluramine increases the risk of pulmonary hypertension in humans, and its active metabolite is a selective serotonin 5-hydroxytryptamine 2B (5-HT(2B)) receptor agonist. Thus, we investigated the contribution of the 5-HT(2B)receptor to the pathogenesis of pulmonary hypertension. Using the chronic-hypoxic-mouse model of pulmonary hypertension, we found that the hypoxia-dependent increase in pulmonary blood pressure and lung remodeling are associated with an increase in vascular proliferation, elastase activity and transforming growth factor-beta levels, and that these parameters are potentiated by dexfenfluramine treatment. In contrast, hypoxic mice with genetically or pharmacologically inactive 5-HT(2B)receptors manifested no change in any of these parameters. In both humans and mice, pulmonary hypertension is associated with a substantial increase in 5-HT(2B) receptor expression in pulmonary arteries. These data show that activation of 5-HT(2B) receptors is a limiting step in the development of pulmonary hypertension.

Current management approaches to portopulmonary hypertension.

Portopulmonary hypertension (PoPH) is a rare but life-threatening complication of portal hypertension that is characterised by proliferative changes in the pulmonary microvasculature indistinguishable from other forms of pulmonary arterial hypertension (PAH). Although PoPH is most commonly observed in the setting of cirrhosis, patients with non-cirrhotic portal hypertension are also at risk of developing the disorder. A definitive diagnosis requires invasive haemodynamic confirmation by right heart catheterisation and screening for PoPH should be routinely performed in all patients being considered for liver transplantation. Although severe PoPH is considered a contraindication to liver transplantation, there is now compelling data supporting the use of PAH-specific therapies with the aim of improving pulmonary haemodynamics to allow transplantation to be successfully performed. This review explores possible relevant aetiological factors and summarises current diagnostic and therapeutic approaches for PoPH patients.

Plasma symmetric dimethylarginine and creatinine concentrations and glomerular filtration rate in cats with normal and decreased renal function.

BACKGROUND: Glomerular filtration rate (GFR) is the gold standard in assessing renal function but is impractical. Serum creatinine (sCr) has limited sensitivity in identifying early chronic kidney disease (CKD), whereas symmetric dimethylarginine (SDMA) has been commercialized as more accurate biomarker. Studies comparing SDMA and sCr with GFR in cats are limited. OBJECTIVES: To further investigate the diagnostic performance of SDMA in nonazotemic and azotemic cats. ANIMALS: Forty-nine client-owned cats: 17 cats with CKD, 15 cats with diabetes mellitus (DM), and 17 healthy cats. METHODS: Retrospective study using spare blood samples from cats with documented sCr and GFR results for SDMA analysis. Diagnostic performances of SDMA and sCr were evaluated using correlation coefficients, sensitivities, specificities, and receiver operator characteristic curves. RESULTS: Compared to healthy cats and cats with DM, CKD cats had significantly higher SDMAplasma (26.7 ± 9.9 µg/dL) and sCr (249.7 ± 71.6 µmol/L [2.8 ± 0.8 mg/dL]; both P < .001) values. SDMAplasma (τB = -0.57; P < .001) and sCr (τB = -0.56; P < .001) were significantly correlated with GFR. SDMAplasma (τB = 0.52; P < .001) had a significant relationship with sCr. SDMAplasma and sCr had similar sensitivity (76%-94% and 71%-88%, respectively) in detecting reduced renal function. Creatinine had higher specificity (94%-96%) than SDMAplasma (75%-76%) (P < .05). CONCLUSION AND CLINICAL IMPORTANCE: In this study of azotemic and nonazotemic cats, SDMA was a reliable marker to identify decreased GFR. However, superiority of SDMA over sCr could not be confirmed.

Safety and immunogenicity of the epicutaneous reactivation of pertussis toxin immunity in healthy adults: a phase I, randomized, double-blind, placebo-controlled trial.

OBJECTIVES: Protection induced by acellular vaccines can be short, requiring novel immunization strategies. Objectives of this study were to evaluate safety and capacity of a recombinant pertussis toxin (PTgen) -coated Viaskin® epicutaneous patch to recall memory responses in healthy adults. METHODS: This double-blind, placebo-controlled randomized trial (Phase I) assessed the safety and immunogenicity of PTgen administered on days 0 and 14 to healthy adults using Viaskin® patches applied directly or after epidermal laser-based skin preparation. Patch administration was followed by Boostrix®dTpa on day 42. Antibodies were assessed at days 0, 14, 28, 42 and 70. RESULTS: Among 102 volunteers enrolled, 80 received Viaskin-PT (Viaskin-PT 25 µg (n = 25), Viaskin-PT 50 µg (n = 25), laser + Viaskin-PT 25 µg (n = 5), laser + Viaskin-PT 50 µg (n = 25)), Viaskin-placebo (n = 10) or laser + Viaskin-placebo (n = 2). Incidence of adverse events was similar across groups (any local event: 21/25 (84.0%), 24/25 (96.0%), 4/5 (80.0%), 24/25 (96.0%), 8/10 (80.0%), 10/12 (83.0%), respectively). Direct application induced no detectable response. On day 42, PT-IgG geometric mean concentrations were significantly higher following laser + Viaskin-PT 25 µg and 50 µg (139.87 (95% CI 87.30-224.10) and 121.76 (95% CI 95.04-156.00), respectively), than laser + Viaskin-placebo (59.49, 95% CI 39.37-89.90). Seroresponse rates were higher following laser + Viaskin-PT 25 µg (4/5 (80.0%), 95% CI 28.4-99.5) and 50 µg (22/25 (88.0%), 95% CI 68.8-97.5) than laser + Viaskin-placebo (0/12 (0.0%), 95% CI 0.0-26.5). CONCLUSIONS: Viaskin-PT applied after laser-based epidermal skin preparation showed encouraging safety and immunogenicity results: anti-PT booster responses were not inferior to those elicited by Boostrix®dTpa. This study is registered at ClinicalTrials.gov (NCT03035370) and was funded by DBV Technologies.

Comparison of Doppler ultrasonography and high-definition oscillometry for blood pressure measurements in healthy awake dogs.

OBJECTIVE: To determine the intra- and interobserver variability of systolic arterial pressure (SAP) and diastolic arterial pressure (DAP) measurements obtained with 2 indirect methods in awake dogs and percentage of successful measurements. ANIMALS: 6 healthy conscious adult dogs. PROCEDURES: 4 observers with different levels of training measured SAP and DAP on 4 days by use of Doppler ultrasonography (DU) and high-definition oscillometry (HDO). The examinations were randomized. Measurements for each technique were recorded 5 consecutive times, and mean values (total, 720 measurements) were used for statistical analysis. RESULTS: All within- and between-day coefficients of variation (CVs) for SAP were < 15% irrespective of the observer or method (HDO, 3.6% to 14.1%; DU, 4.1% to 12.4%). Conversely, half the CVs for DAP were > 15% with the highest within- and between-day CVs obtained by the least experienced observer by use of DU (19.5% and 25.9%, respectively). All attempts with HDO were successful, whereas DAP could not be measured by use of DU by the least experienced observer in 17% of attempts. CONCLUSIONS AND CLINICAL RELEVANCE: SAP may be assessed in healthy dogs by use of DU and HDO with good repeatability and reproducibility after a short period of training. Conversely, the variability of DAP is higher and longer training is required to assess DAP via DU than via HDO.

Nitric oxide production by the alveolar compartment of the lungs in cirrhotic patients.

In cirrhotic patients, alveolar nitric oxide (NO) concentration is increased. This may be secondary to increased output of NO produced by the alveoli (V'(A,NO)) and/or to decreased lung transfer factor of NO. In advanced liver cirrhosis, NO produced by the alveoli may play a role in abnormalities of pulmonary haemodynamics and gas exchanges. In cirrhotic patients, we aimed to measure V'(A,NO) and to compare V'(A,NO) with pulmonary haemodynamics and gas exchange parameters. Measurements were performed in 22 healthy controls and in 29 cirrhotic patients, of whom eight had hepatopulmonary syndrome. Exhaled NO concentrations were measured at multiple expiratory flow rates to derive alveolar NO concentration. V'(A,NO) was the product of alveolar NO concentration by single breath lung transfer factor for NO. V'(A,NO) was increased in patients (median (range) 260 (177-341) nL x min(-1)) compared with controls (79 (60-90), p<0.0001). Alveolar-arterial oxygen tension difference failed to correlate with V'(A,NO). However, cardiac index correlated positively and systemic vascular resistance correlated negatively with V'(A,NO) (r = 0.56, p = 0.001 and r = -0.52, p = 0.004, respectively). In cirrhotic patients, NO was produced in excess by the alveolar compartment of the lungs. Alveolar NO production was associated with hyperdynamic circulatory syndrome but not with arterial oxygenation impairment.

Cirrhosis ameliorates monocrotaline-induced pulmonary hypertension in rats.

Common bile duct ligation (CBDL) induces biliary cirrhosis and pulmonary vasodilatation. We tested whether CBDL ameliorates monocrotaline (MCT)-induced pulmonary hypertension (PH) in rats. Five groups of rats were studied: controls; rats dosed with MCT (60 mg.kg(-1) subcutaneously); CBDL; rats dosed with MCT followed by CBDL on day 7; and rats dosed with MCT followed by CBDL (day 7) and L-NAME therapy between days 24 and 28. 28-day survival was 26% in the MCT group and 72% in the MCT+CBDL group. Pulmonary vascular resistance measured on days 21 and 28 increased in the MCT and MCT+CBDL+L-NAME groups, but returned to normal in the MCT+CBDL group on day 28. Pulmonary artery (PA) medial hypertrophy persisted in MCT+CBDL rats. PA inflammation increased in MCT+CBDL rats, with accumulation of both intra- and perivascular macrophages. Exhaled nitric oxide (NO) levels decreased in the MCT group and increased in the MCT+CBDL group, which showed upregulation of inducible NO synthase and normal endothelial NO synthase. Blood endothelin (ET)-1 increased in CBDL, MCT, and MCT+CBDL rats. Levels of ET(B) receptors increased and ET(A) receptors decreased in the MCT+CBDL group, whereas the opposite changes occurred in the MCT group. Biliary cirrhosis induces pulmonary vasodilation that ameliorates MCT-induced PH and improves survival. Upregulation of inducible NO synthase and ET(B) receptor and downregulation of ET(A) receptor may be involved.

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.

Development of a dual infrared and visible near-infrared measurement system for the observation of adiabatic shear bands.

This paper presents the development of a new system designed to measure the local temperature field in adiabatic shear bands. Transient temperature fields are simultaneously recorded by using an array of 32 InSb infrared (IR) detectors and a streak camera working in visible-near infrared (VIS-NIR). Observations in IR offer a low temperature detection limit (550 K), but they are highly sensitive to uncertainties in emissivity. Observations in VIS-NIR allow for measurements only at high temperatures (>1000 K), but they are less affected by uncertainties in emissivity and present a higher temperature sensitivity. By performing simultaneous measurements, it is possible to obtain data in a large temperature range with an improved accuracy at high temperature. The different sources of error caused by uncertainties in emissivity, spatial resolution, and temporal resolution have been analyzed, and an estimation of the total measurement uncertainties of the system is given.

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.

Changes in exercise haemodynamics during treatment in pulmonary arterial hypertension.

Improvement in exercise capacity may not be associated with significant changes in resting pulmonary haemodynamics. The present prospective study documented the relationships between improvement in 6-min walking distance (6MWD) and changes in resting and exercise pulmonary haemodynamics after treatment in patients with idiopathic pulmonary arterial hypertension (IPAH). A total of 42 IPAH patients underwent supine submaximal exercise haemodynamic assessments at baseline and after 5+/-2 months of therapy. The 6MWD, the corresponding chronotropic response (peak minus resting heart rate), and resting and exercise haemodynamic variables were analysed. The isoflow was defined as the lowest of the pre- and post-treatment peak cardiac index (CI). The extrapolated isoflow mean pulmonary artery pressure ((pa)) was used to characterise changes in (pa)-CI regression lines following treatment. Patients were given bosentan (n = 28), epoprostenol (n = 12) or both. The 6MWD increased significantly, from 399+/-88 to 442+/-86 m. On univariate analysis, changes in 6MWD correlated with changes in isoflow (pa), chronotropic response, resting haemodynamics (CI, pulmonary vascular resistance and mixed venous oxygen saturation) and exercise haemodynamics (peak CI). On multivariate analysis, only changes in isoflow (pa) and chronotropic response were independently associated with changes in 6MWD. Improvement in exercise tolerance with chronic therapy is independently related to improvement in pulmonary haemodynamics measured in exercise but not in resting conditions.

Pulmonary arterial hypertension associated with fenfluramine exposure: report of 109 cases.

The aim of the present study was to describe a large cohort of fenfluramine-associated pulmonary arterial hypertension (fen-PAH) and its possible prognostic markers. The records of all patients with a diagnosis of fen-PAH evaluated at the present authors' centre from 1986-2004 were retrospectively studied. Baseline clinical and haemodynamic data were collected, as well as survival times. The median duration of fenfluramine exposure was 6 months, with a median of 4.5 yrs between exposure and onset of symptoms. Nine (22.5%) out of 40 patients evaluated resulted positive for the presence of germline bone morphogenetic protein receptor (BMPR) type 2 mutations. In these patients, the duration of exposure to fenfluramine was significantly lower than in patients without mutation. The median survival was 6.4 yrs, without significant difference between fen-PAH and a control group of idiopathic and familial pulmonary arterial hypertension patients referred to the present authors' centre during the same time frame and treated identically. Duration of fenfluramine exposure showed no relation to survival, while cardiac index was the only independent predictor of multivariate analysis. Fenfluramine-associated pulmonary arterial hypertension shares clinical, functional, haemodynamic and genetic features with idiopathic pulmonary arterial hypertension, as well as overall survival rates. Therefore, the present authors conclude that fenfluramine exposure characterises a potent trigger for pulmonary arterial hypertension without influencing its clinical course.

Determination of reference intervals for plasma biochemical values in clinically normal adult domestic shorthair cats by use of a dry-slide biochemical analyzer.

OBJECTIVE: To establish reference intervals of plasma biochemical values in healthy adult domestic shorthair (DSH) cats by use of controlled conditions. ANIMALS: 95 healthy client-owned cats. PROCEDURES: Food was withheld from the cats overnight. All blood samples were obtained on the same day, at the same location, and by the same investigator. Blood samples were collected from a cephalic vein into lithium heparin tubes. After centrifugation of blood samples, plasma supernatants were harvested and stored at -20 degrees C until assayed for total proteins, albumin, creatinine, urea, glucose, calcium, phosphates, sodium, chloride, potassium, and CO2 concentrations and alkaline phosphatase and alanine aminotransferase activities. RESULTS: Reference intervals in healthy adult DSH cats were 65 to 85 g/L for total proteins, 27 to 39 g/L for albumin, 89 to 207 micromol/L for creatinine, 6.6 to 11.3 mmol/L for urea, 4.1 to 8.2 mmol/L for glucose, 2.4 to 2.9 mmol/L for calcium, 1.1 to 2.1 mmol/L for phosphates, 153 to 161 mmol/L for sodium, 120 to 127 mmol/L for chloride, 3.3 to 4.2 mmol/L for potassium, 15 to 21 mmol/L for CO2, 32 to 147 U/L for alkaline phosphatase, and 34 to 123 U/L for alanine aminotransferase. CONCLUSIONS AND CLINICAL RELEVANCE: This study provided reference intervals for plasma analytes in adult DSH cats. The influence of potential confounding factors was minimized through use of controlled preanalytic and analytic conditions. However, these results cannot be extrapolated to other feline breeds or used to interpret results from other biochemical analyzers.

Comparison of a new blood sampling device with the vacuum tube system for plasma and hematological analyses in healthy dogs.

Pediatric devices based on a capillary system may provide an alternative to vacuum tubes for canine blood sampling. The potential advantages are absence of vein collapse, limited blood volume sampled, and improved safety. The aim of this study was to compare routine plasma and hematological variables in seven healthy dogs using both techniques. Five biochemical analytes were measured, and a complete hematological examination and plasma exogenous creatinine clearance test were performed. No clinically relevant difference between the two techniques was observed for any variable or functional test assessed.