Sensitivity and Specificity of Plasma ALT, ALP, and Bile Acids for Hepatitis in Labrador Retrievers.

BACKGROUND: Biochemical indicators for diagnosing liver disease are plasma alanine aminotransferase activity (ALT), alkaline phosphatase activity (ALP), and bile acid concentration (BA). OBJECTIVES: To determine the sensitivity and specificity of ALT, ALP, and BA for detecting primary hepatitis (PH) in clinically healthy Labrador retrievers and investigate whether ALT and ALP can discriminate between dogs with PH and nonspecific reactive hepatitis (RH). ANIMALS: 191 clinically healthy and 51 clinically ill Labrador retrievers with hepatic histopathology. METHODS: Retrospective study. Medical records were reviewed for ALT, ALP, preprandial BA, liver histopathology, and hepatic copper concentrations. RESULTS: In 64% (122/191) of the clinically healthy Labrador retrievers, hepatic histology revealed inflammatory infiltrates. This frequency might be biased because part of them was included as first-line relatives of dogs with copper-associated hepatitis. Sensitivity of ALT, ALP, and BA in this population for detecting acute hepatitis was 45, 15, and 15%, respectively. For chronic hepatitis, sensitivity was 71, 35, and 13%, respectively. Specificity of ALT, ALP, and BA was >90% for AH, CH, and RH. When increased liver enzymes were present, median ALT was significantly higher in PH cases (312 U/L, range 38-1,369) compared to RH cases (91 U/L, range 39-139) (P < .001). There was no difference in ALP between dogs with a PH and a RH (P = .361). CONCLUSIONS AND CLINICAL IMPORTANCE: Histopathologic abnormalities in the liver were present in the majority of apparent clinically healthy Labrador retrievers. The sensitivity of ALT, ALP, and BA for detecting acute and chronic hepatitis in this population was low. More sensitive biomarkers are needed for early detection of liver disease in apparent clinically healthy dogs.

Erythrocyte copper chaperone for superoxide dismutase and superoxide dismutase as biomarkers for hepatic copper concentrations in Labrador retrievers.

Hereditary hepatic copper accumulation in Labrador retrievers leads to hepatitis with fibrosis and eventually cirrhosis. The development of a non-invasive blood-based biomarker for copper status in dogs could be helpful in identifying dogs at risk and to monitor copper concentrations during treatment. In this study, two cellular copper metabolism proteins, Cu/Zn superoxide dismutase (SOD1) and its chaperone (copper chaperone for SOD1, CCS) were measured in erythrocytes and tested for association with hepatic copper concentrations in 15 Labrador retrievers with normal or increased hepatic copper concentrations. Antibodies against CCS and SOD1 were applicable for use in canine specimens. This was demonstrated by the loss of immune-reactive bands for CCS and SOD1 in siRNA treated canine bile duct epithelial cells. Erythrocyte CCS and CCS/SOD1 ratios were decreased 2.37 (P <0.001) and 3.29 (P <0.001) fold in the high copper group compared to the normal copper group. Erythrocyte CCS and CCS/SOD1 ratio are potential new biomarkers for hepatic copper concentrations in Labrador retrievers and could facilitate early diagnosis and treatment monitoring for copper-associated hepatitis in dogs.

Use of Serum MicroRNAs as Biomarker for Hepatobiliary Diseases in Dogs.

BACKGROUND: Current biochemical indicators cannot discriminate between parenchymal, biliary, vascular, and neoplastic hepatobiliary diseases. MicroRNAs are promising new biomarkers for hepatobiliary disease in humans and dogs. OBJECTIVE: To measure serum concentrations of an established group of microRNAs in dogs and to investigate their concentrations in various types of hepatobiliary diseases. ANIMALS: Forty-six client-owned dogs with an established diagnosis of hepatobiliary disease and stored serum samples and eleven client-owned healthy control Labrador Retrievers. METHODS: Retrospective study. Medical records of dogs with parenchymal, biliary, vascular, or neoplastic hepatobiliary diseases and control dogs were reviewed. Concentrations of miR-21, miR-122, miR-126, miR-148a, miR-200c, and miR-222 were quantified in serum by real-time polymerase chain reaction. RESULTS: No different microRNA concentrations were found in the adenoma and congenital portosystemic shunt groups. In all other diseases, miR-122 concentrations were elevated with the highest concentration in the mucocele group (267-fold, CI: 40-1,768, P < .001). In dogs with biliary diseases, miR-21 and miR-222 were only increased in dogs with mucoceles (26-fold, CI: 5-141, P = .005 and 13-fold, CI: 2-70, P = .025, respectively). Uniquely increased microRNAs were found in the hepatocellular carcinoma group (miR-200c, 35-fold increase, CI: 3-382, P = .035) and the chronic hepatitis group (miR-126, 22-fold increase, CI: 5-91, P = .002). CONCLUSIONS AND CLINICAL IMPORTANCE: A microRNA panel consisting of miR-21, miR-122, miR-126, miR-200c, and miR-222 can distinguish between parenchymal, biliary, and neoplastic hepatobiliary diseases. Serum microRNA profiling is a promising new tool that might be a valuable addition to conventional diagnostics to help diagnose various hepatobiliary diseases in dogs.

Hepatocyte-derived microRNAs as sensitive serum biomarkers of hepatocellular injury in Labrador retrievers.

Common parenchymal liver diseases in dogs include reactive hepatopathies and primary hepatitis (acute or chronic). In chronic hepatitis, there is usually a long subclinical phase. Specific clinical signs become overt only when liver damage is severe and in this phase, treatment is usually less effective. Limited data are available regarding the sensitivity of liver enzyme activity or biomarkers for early detection of subclinical hepatitis. Hepatocyte-derived microRNAs (HDmiRs) were recently identified as promising biomarkers for hepatocellular injury in multiple species. Here, the potential of the HDmiRs miR-122 and miR-148a as sensitive diagnostic biomarkers for hepatocellular injury in Labrador retrievers was investigated. Samples from 66 Labrador retrievers with histologically normal livers, high hepatic copper, and with various forms of liver injury were evaluated for serum alanine aminotransferase (ALT) activity and microRNA values. Median values of HDmiR-122 were 34.6 times higher in dogs with liver injury and high ALT than in normal dogs (95% confidence intervals [CI], 13-95; P <0.001). HDmiR-122 values were significantly increased in dogs with liver injury and normal ALT (4.2 times; 95% CI, 2-12; P <0.01) and in dogs with high hepatic copper concentrations and unremarkable histopathology (2.9 times; 95% CI, 1.1-8.0; P <0.05). Logistic regression analyses demonstrated that miR-122 and miR-148a were both predictors of hepatocellular injury. The sensitivity of miR-122 was 84% (95% CI, 73-93%), making it superior to ALT (55%; 95% CI, 41-68%) for the detection of hepatocellular injury in Labrador retrievers (P <0.001). This study demonstrated that serum HDmiR, particularly miR-122, is a highly sensitive marker for the detection of hepatocellular injury in Labrador retrievers and is a promising new biomarker that may be used for early detection of subclinical hepatitis in dogs.

Middle East respiratory syndrome coronavirus (MERS-CoV) infections in two returning travellers in the Netherlands, May 2014.

Two patients, returning to the Netherlands from pilgrimage in Medina and Mecca, Kingdom of Saudi Arabia, were diagnosed with Middle East respiratory syndrome coronavirus (MERS-CoV) infection in May 2014. The source and mode of transmission have not yet been determined. Hospital-acquired infection and community-acquired infection are both possible.

The value of scintigraphy in hips with slipped capital femoral epiphysis and the value of radiography and MRI after 10 years.

Preoperative bone scintigraphy of the femoral head in 33 hips with slipped capital femoral epiphysis, showed no relation to duration of symptoms or degree of slip. The preoperative uptake was always normal or increased. Two hips had postoperative femoral head uptake below normal, both had complications affecting the vascular supply, resulting in necrosis of the femoral head and severe arthrosis. At follow-up after 10 (5-15) years of 28 hips, no relation could be demonstrated between Adolescent Hip Questionnaire which included clinical data, and radiography or magnetic resonance imaging. We only recommend scintigraphy after complications jeopardizing the vascular supply of the femoral head in slipped capital femoral epiphysis.

Rectal salmon calcitonin for the treatment of postmenopausal osteoporosis.

In a 2-year study, we examined bone mass and calcium metabolism in 36 elderly women with moderate osteoporosis. The study period comprised 1 year of observation, during which the women received no treatment affecting calcium metabolism, and 1 year of treatment, during which all participants received daily salmon calcitonin (sCT) 100 IU rectally and calcium 500 mg. During the observational period a significant bone loss of 1.5% was seen in the forearm (P less than 0.01), whereas the spinal bone mass was virtually unchanged. After institution of treatment, the bone loss was arrested in the forearm and a significant increase of about 2% was seen in the spine (P less than 0.01). The net effect of treatment revealed a positive outcome in both bone compartments (1.9% and 2.9%, P less than 0.05-0.01). Correspondingly, the parameters of bone turnover (serum alkaline phosphatase, plasma bone Gla protein, and fasting urinary hydroxy-proline/creatinine) did not change during the observational period, but significantly declined, 10-30%, during sCT treatment (P less than 0.01-0.001). Tolerance was generally good, although in one woman, anoscopy revealed irritative changes in the rectal mucosa. We conclude that, given rectally, sCT is well absorbed and well tolerated and that it has a beneficial effect on calcium metabolism in moderately osteoporotic women.

[Angiomyolipomas in the kidney. A review]. / Angiomyolipomer i nyren. En oversigt.

Renal angiomyolipomata are rare, benign hamartomata composed of various amounts of fat, smooth muscle and blood vessels. The tumours may have an extremely variable clinical presentation which may be difficult to distinguish from other renal disorders. By combining the use of ultrasound- and CT-scanning, it is possible to make a definite diagnosis thus obviating usually unnecessary nephrectomy. Only symptomatic tumours require treatment. The treatment is directed mainly towards preventing or stopping bleeding. In cases where intervention is considered to be indicated, embolization should be carried out if possible. Otherwise, the renal surgery should preserve as much of the kidney as possible. Nephrectomy is indicated only for uncontrollable life-threatening bleeding, tumours which involve the whole kidney or in the presence of simultaneous carcinoma.

Cardiac complications of intravenous digital subtraction angiography.

In a prospective study of 103 patients the incidence of cardiac events during intravenous digital subtraction angiography (i. v. DSA) was investigated. Of 103 patients 17 had known ischaemic heart disease. The examination was performed with an ionic contrast medium, Urografin 76% (sodium megluminediatrizoate), administered by bolus injection into the right atrium. Patients with severe cardiac disease were examined only if the procedure was considered of vital importance. Cardiac events were defined as ST-segment changes of more than 0.1 mV, changes in heart rate of more than 20%, arrhythmias and such symptoms as chest pain and dyspnoea. Ischaemic ST-segment changes during i. v. DSA were observed in approximately 20% of the patients and were not related to the presence of known ischaemic heart disease. Three patients developed angina during the procedure. Among 12 patients with known angina only one patient developed angina during the procedure. In this study chest pain was infrequent (3%), but there was a relative high frequency of ECG changes (20%) not related to patients with ischaemic heart disease only. It is concluded that there is a risk of cardiac events during i. v. DSA, but the risk is not increased in patients with known ischaemic heart disease (if they do not suffer from congestive heart failure) as compared with other patients without known ischaemic heart disease.

Collagen components in the duodenal and rectal mucosa in progressive systemic sclerosis and other diseases.

Small intestinal mucosa from 14 patients suffering from progressive systemic sclerosis and 22 patients with various other diseases was analysed for collagen components. There was no significant difference in the concentration of hydroxyproline, hydroxylysine and proline between the two groups. Rectal mucosa from 11 progressive systemic sclerosis patients, 5 patients with ulcerative colitis and 7 patients with various other diseases was analysed for collagen components. No significant difference was demonstrated in the concentration of hydroxyproline, hydroxylysine and proline between progressive systemic sclerosis patients and patients with various other diseases, but in patients with ulcerative colitis the concentration of hydroxyproline, hydroxylysine and proline were found to be significantly lower than in the two other groups.

Collagen in the esophageal mucosa of patients with progressive systemic sclerosis (PSS).

Eighteen consecutive patients with an established diagnosis of Progressive Systemic Sclerosis (PSS) underwent different investigative procedures to determine possible esophageal involvement. Esophageal sclerosis was demonstrated by X-ray and manometry in 13 patients. In all patients endoscopic biopsies of esophageal mucosa were obtained. In all biopsies the concentrations of hydroxyproline, hydroxylysine and proline were determined. Patients suffering from PSS involving the esophagus were found to have a significantly higher concentration of collagen specific amino acids (hydroxyproline and hydroxylysine) in the esophageal mucosa (endoscopic obtainable biopsies) than patients with PSS not affecting the esophagus.