Cardiac Troponin I and Amino-Terminal Pro B-Type Natriuretic Peptide in Dogs With Stable Chronic Kidney Disease.

BACKGROUND: Increased concentrations of N-terminal pro B-type natriuretic peptide (NT-proBNP) and cardiac troponin I (cTnI) in dogs with azotemia have been documented. Knowledge of mechanisms behind increased concentrations of cardiac biomarkers in dogs with azotemia is warranted for correct interpretation of test results. OBJECTIVES: The aim of the article was to investigate possible associations between plasma concentrations of cTnI and NT-proBNP, respectively, and patient characteristics, glomerular filtration rate (GFR), a plasma volume factor (PVF) derived from scintigraphic examination (PVf), systolic blood pressure (SBP), selected hematologic and biochemical variables, and echocardiographic measurements in dogs with stable chronic kidney disease (CKD) and in healthy dogs. ANIMALS: Fifty student-, staff-, and client-owned dogs were included. Twenty-three of the dogs were healthy and 27 were diagnosed with CKD. METHODS: In this cross-sectional observational study, dogs with a previous diagnosis of CKD and healthy control dogs were included. At inclusion, all dogs were characterized by physical examination, repeated blood pressure measurements, complete urinalysis, hematology and biochemistry panel, echocardiography, abdominal ultrasound examination of the entire urinary tract, and scintigraphic examination for measurement of GFR. RESULTS: Plasma volume factor and PCV were independently associated with NT-proBNP (Radj2 = 0.42; P < .0001). Age, body weight (BW), and SBP were independently associated with cTnI (Radj2 = 0.50; P < .0001). CONCLUSIONS AND CLINICAL IMPORTANCE: Neither NT-proBNP nor cTnI concentrations were independently associated with measured GFR. Thus, findings were not suggestive of passive accumulation of either marker, suggesting that increased circulating concentrations of cTnI and NT-proBNP can be interpreted similarly in dogs with stable CKD as in dogs without CKD.

Osteochondrosis, Synovial Fossae, and Articular Indentations in the Talus and Distal Tibia of Growing Domestic Pigs and Wild Boars.

Articular osteochondrosis (OC) often develops in typical locations within joints, and the characterization of OC distribution in the pig tarsus is incomplete. Prevalence of OC is high in domestic pigs but is presumed to be low in wild boars. Postmortem and computed tomography (CT) examinations of the talus and distal tibia from 40 domestic pigs and 39 wild boars were evaluated for the locations and frequencies of OC, synovial fossae, and other articular indentations, and frequency distribution maps were made. All domestic pigs but only 5 wild boars (13%) had OC on the talus. In domestic pigs, OC consistently affected the axial aspect of the medial trochlea tali in 11 (28%) joints and the distomedial talus in 26 (65%) joints. In wild boars, all OC lesions consistently affected the distomedial talus. On the articular surface of the distal tibia, all domestic pigs and 34 wild boars (87%) had synovial fossae and 7 domestic pigs (18%) had superficial cartilage fibrillation opposite an OC lesion (kissing lesion). Other articular indentations occurred in the intertrochlear groove of the talus in all domestic pigs and 13 wild boars (33%) and were less common on the trochlea tali. The prevalence of tarsal OC in wild boars is low. In domestic pigs and wild boars, OC is typically localized to the distomedial talus and in domestic pigs also to the medial trochlea tali. Further investigations into the reasons for the low OC prevalence in wild boars may help in developing strategies to reduce OC incidence in domestic pigs.

Detection of early osteoarthritis in the centrodistal joints of Icelandic horses: Evaluation of radiography and low-field magnetic resonance imaging.

REASONS FOR PERFORMING STUDY: Validated noninvasive detection methods for early osteoarthritis (OA) are required for OA prevention and early intervention treatment strategies. OBJECTIVES: To evaluate radiography and low-field magnetic resonance imaging (MRI) for the detection of early stage OA osteochondral lesions in equine centrodistal joints using microscopy as the reference standard. STUDY DESIGN: Prospective imaging of live horses and imaging and microscopy of cadaver tarsal joints. METHODS: Centrodistal (distal intertarsal) joints of 38 Icelandic research horses aged 27-29 months were radiographed. Horses were subjected to euthanasia approximately 2 months later and cadaver joints examined with low-field MRI. Osteochondral joint specimens were classified as negative or positive for OA using light microscopy histology or scanning electron microscopy. Radiographs and MRIs were evaluated for osteochondral lesions and results compared with microscopy. RESULTS: Forty-two joints were classified OA positive with microscopy. Associations were detected between microscopic OA and the radiography lesion categories; mineralisation front defect (P<0.0001), joint margin lesion (P<0.0001), central osteophyte (P = 0.03) and the low-field MRI lesion categories; mineralisation front defect (P = 0.01), joint margin lesion (P = 0.02) and articular cartilage lesion (P = 0.0003). The most frequent lesion category detected in microscopic OA positive joints was the mineralisation front defect in radiographs (28/42 OA positive joints, specificity 97%, sensitivity 67%). No significant differences were detected between the sensitivity and specificity of radiography and low-field MRI pooled lesion categories, but radiography was often superior when individual lesion categories were compared. CONCLUSIONS: Early stage centrodistal joint OA changes may be detected with radiography and low-field MRI. Detection of mineralisation front defects in radiographs may be a useful screening method for detection of early OA in centrodistal joints of young Icelandic horses.

Osteochondral lesions in distal tarsal joints of Icelandic horses reveal strong associations between hyaline and calcified cartilage abnormalities.

Osteochondral lesions in the joints of the distal tarsal region of young Icelandic horses provide a natural model for the early stages of osteoarthritis (OA) in low-motion joints. We describe and characterise mineralised and non-mineralised osteochondral lesions in left distal tarsal region joint specimens from twenty-two 30 ±1 month-old Icelandic horses. Combinations of confocal scanning light microscopy, backscattered electron scanning electron microscopy (including, importantly, iodine staining) and three-dimensional microcomputed tomography were used on specimens obtained with guidance from clinical imaging. Lesion-types were described and classified into groups according to morphological features. Their locations in the hyaline articular cartilage (HAC), articular calcified cartilage (ACC), subchondral bone (SCB) and the joint margin tissues were identified and their frequency in the joints recorded. Associations and correlations between lesion-types were investigated for centrodistal joints only. In centrodistal joints the lesion-types HAC chondrocyte loss, HAC fibrillation, HAC central chondrocyte clusters, ACC arrest and ACC advance had significant associations and strong correlations. These lesion-types had moderate to high frequency in centrodistal joints but low frequencies in tarsometatarsal and talocalcaneal-centroquartal joints. Joint margin lesion-types had no significant associations with other lesion-types in the centrodistal joints but high frequency in both the centrodistal and tarsometatarsal joints. The frequency of SCB lesion-types in all joints was low. Hypermineralised infill phase lesion-types were detected. Our results emphasise close associations between HAC and ACC lesions in equine centrodistal joints and the importance of ACC lesions in the development of OA in low-motion compression-loaded equine joints.

Insulin resistance, lipoproteins, body fat and hemostasis in nonobese men with angina and a normal or abnormal coronary angiogram.

OBJECTIVES: The aim of this study was to compare metabolic risk factors in men with anginal chest pain and a normal or abnormal coronary angiogram with those in healthy men. BACKGROUND: Risk factors for coronary heart disease, including lipoprotein abnormalities, hypertension and adiposity, may be metabolically interlinked, with insulin resistance and hyperinsulinemia being pivotal to these disturbances. METHODS: Glucose and insulin metabolism, lipids and lipoproteins, hemostasis, blood pressure and body fat distribution were measured in 77 nonobese middle-aged men who had anginal chest pain (39 with an abnormal coronary angiogram and 38 with no detectable angiographic abnormality) and were compared with those of 40 healthy men of similar age and body mass index. RESULTS: Patients with chest pain had higher insulin responses to an intravenous glucose challenge, lower insulin sensitivity, lower high density lipoprotein (HDL) and subfraction 2 cholesterol, lower apolipoprotein AI, higher triglycerides, greater android fat and higher systolic blood pressure at rest compared with levels in healthy control subjects (p < 0.05). Those with an abnormal coronary angiogram had lower tissue plasminogen activator levels, higher plasminogen activator inhibitor 1 levels and more android fat than did those with a normal angiogram (p < 0.05). Insulin sensitivity correlated positively with HDL (p < 0.05) and subfraction 2 (p < 0.001) cholesterol and negatively with triglycerides (p < 0.01), android fat proportion (p < 0.01) and systolic blood pressure (p < 0.05), whereas insulin response showed converse correlations. CONCLUSIONS: These findings provide new evidence of the central role of insulin resistance and hyperinsulinemia in the development of risk factors associated with coronary heart disease.

Sex- and menopause-associated changes in body-fat distribution.

We investigated sex- and menopause-related differences in body composition and regional fat distribution, using dual-energy X-ray absorptiometry (DEXA) in nonobese healthy volunteers. Men (n = 103) had a 50% greater lean tissue mass (P less than 0.001) but a 13% lower fat mass (P less than 0.001) than the women (n = 131). Postmenopausal (n = 70) women had a 20% greater fat mass (P less than 0.001) than premenopausal (n = 61) women. The proportion of android (upper body) fat was greatest in men (48.6%, P less than 0.001) but was significantly lower in premenopausal (38.3%) than in postmenopausal (42.1%) women (P less than 0.001). The reverse was found for gynoid (lower body) fat (P less than 0.001). DEXA measurements thus clearly demonstrated that sex differences in total fat mass were opposite those of android fat, and that marked menopausal changes in fat mass and its distribution existed. Body mass indices did not demonstrate that men had less total fat than women whereas postmenopausal women had more total fat than did premenopausal women. Our findings suggest that DEXA measurements of fat distribution may be useful for studies related to obesity-associated disease risk.

Hormonal and metabolic changes during hypothermic coronary artery bypass surgery in diabetic and non-diabetic subjects.

Hormonal and metabolic responses to hypothermic coronary artery bypass grafting (CABG) were studied in three groups: 8 non-diabetic patients, 8 patients with non-insulin-dependent diabetes mellitus (NIDDM) given a glucose pump priming solution and 8 NIDDM patients given a non-glucose infusion. There were no significant differences in stress hormone responses between NIDDM and non-diabetic patients, with adrenaline concentrations rising 10-fold, noradrenaline 4-fold and cortisol 2 to 3-fold. Glucagon rose significantly during bypass only in the NIDDM patients who did not receive a glucose prime. Comparable marked hyperglycaemia was seen in both glucose primed groups during bypass and exclusion of glucose from the prime in NIDDM patients prevented this major rise. Postoperatively, the rise in insulin in the glucose primed NIDDM patients contrasted with the slower rise in the non-glucose primed NIDDM patients who were also hyperglycaemic by this stage. Perioperative hyperglycaemia in NIDDM patients undergoing CABG can be prevented by using a non-glucose priming solution and by giving insulin infusion, particularly postoperatively.

The clinical effects of mixing short- and intermediate-acting insulins in the treatment of non-insulin-dependent diabetes.

Premixing short- and intermediate-acting insulins in one syringe, with refrigerated storage before injection, is practised by some centres in the treatment of older patients with non-insulin-dependent diabetes. Because other studies have reported the loss of the short-acting insulin component after mixing with intermediate-acting insulins, we examined the clinical effect of mixing soluble insulin with lente or isophane insulins in subjects with non-insulin-dependent diabetes. When soluble and lente insulins were mixed in the same syringe and injected immediately, the peak level of insulin was very similar to the peak level after separate injections but occurred at five hours instead of three hours after the injection. As a result, the plasma free-insulin profile over three hours was lower with premixed insulin than after separate injections of the two insulins (incremental insulin area, 88 +/- 20 mU.L-1.h, and 129 +/- 37 mU.L-1.h, respectively; P less than 0.05). This delay in the absorption of soluble insulin caused a greater rise in plasma glucose levels such that the incremental glucose area over eight hours was 25.5 +/- 4.4 mmol.L-1.h for premixed insulin compared with 10.4 +/- 6.2 mmol.L-1.h for separate injections (P less than 0.05). Soluble and isophane insulins had similar absorption profiles whether injected separately or premixed (incremental insulin area, 0 to 3 h, 176 +/- 44 mU.L-1.h and 156 +/- 29 mU.L-1.h, respectively). Our results indicate that the absorption of soluble insulin is delayed when it is mixed with lente insulin but not with isophane insulin. Even in subjects with endogenous insulin secretion, this effect may have clinical importance and should be taken into account when insulin therapy is adjusted for patients with non-insulin-dependent diabetes.

Nesidioblastosis and multifocal pancreatic islet cell hyperplasia in an adult. Clinicopathologic features and in vitro pancreatic studies.

The clinicopathologic features of an adult with insulinoma and pancreatic islet cell hyperplasia, who presented with hyperinsulinemic hypoglycemia are reported, together with in vitro studies on the patient's pancreatic islets. Islet cell hyperplasia with ductal proliferation and budding and beta cell degranulation was demonstrated by immunochemical means. The in vitro studies of cultured hyperplastic islet cells support the clinicopathologic features. Thus, in comparison with control islets maintained in culture for up to 14 days, hyperplastic islets could be cultured for up to 60 days, during which time cell overgrowth required subculture on three occasions. Furthermore, in contrast to control islets the release of both insulin and somatostatin from cultured hyperplastic islets was refractory to glucose, glucagon, and tolbutamide; theophylline was the only secretagogue to stimulate insulin and somatostatin release from hyperplastic islets in vitro. Indirect immunofluorescence revealed the presence of islet cell surface autoantibodies in the plasma of this patient reactive with both normal human islets and a rat insulinoma line (RIN-m5F). These studies demonstrate the proliferative capacity and relatively undifferentiated functional state of hyperplastic islets in vitro. They provide further evidence that islet cell division is capable of being stimulated in adult life. The pathogenic significance of islet cell surface autoantibodies in hyperplastic islet cell disease and insulinoma warrants further investigation.