Risk factors associated with cast complications in horses: 398 cases (1997-2006)

OBJECTIVE To determine the frequency of and risk factors for complications associated with casts in horses. DESIGN Multicenter retrospective case series. ANIMALS 398 horses with a half-limb or full-limb cast treated at 1 of 4 hospitals. PROCEDURES Data collected from medical records included age, breed, sex, injury, limb affected, time from injury to hospital admission, surgical procedure performed, type of cast (bandage cast [BC; fiberglass tape applied over a bandage] or traditional cast [TC; fiberglass tape applied over polyurethane resin-impregnated foam]), limb position in cast (flexed, neutral, or extended), and complications. Risk factors for cast complications were identified via multiple logistic regression. RESULTS Cast complications were detected in 197 of 398 (49%) horses (18/53 [34%] horses with a BC and 179/345 [52%] horses with a TC). Of the 197 horses with complications, 152 (77%) had clinical signs of complications prior to cast removal; the most common clinical signs were increased lameness severity and visibly detectable soft tissue damage Cast sores were the most common complication (179/398 [45%] horses). Casts broke for 20 (5%) horses. Three (0.8%) horses developed a bone fracture attributable to casting Median time to detection of complications was 12 days and 8 days for horses with TCs and BCs, respectively. Complications developed in 71%, 48%, and 47% of horses with the casted limb in a flexed, neutral, and extended position, respectively. For horses with TCs, hospital, limb position in the cast, and sex were significant risk factors for development of cast complications. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that 49% of horses with a cast developed cast complications.

INI1 (BAF 47) immunohistochemistry is an essential diagnostic tool for children with hepatic tumors and low alpha fetoprotein

Malignant rhabdoid tumor (MRT) of the liver is a rare malignancy with grave prognosis. This entity should be considered in the differential diagnosis of any aggressive liver tumor with low levels of alpha fetoprotein. We report 2 cases of hepatic MRT presenting in infancy. In these 2 cases, we show that loss of INI1 facilitates making the correct diagnosis of primary hepatic MRT utilizing BAF 47 (INI1 gene product) immunostains. Difficulty encountered in making this rare diagnosis, including the need for repeated biopsies, can be avoided if MRT is considered in the differential diagnosis early on and BAF 47 immunohistochemistry is ordered.

Meta-analysis identifies 29 additional ulcerative colitis risk loci, increasing the number of confirmed associations to 47

Genome-wide association studies and candidate gene studies in ulcerative colitis have identified 18 susceptibility loci. We conducted a meta-analysis of six ulcerative colitis genome-wide association study datasets, comprising 6,687 cases and 19,718 controls, and followed up the top association signals in 9,628 cases and 12,917 controls. We identified 29 additional risk loci (P < 5 × 10(-8)), increasing the number of ulcerative colitis-associated loci to 47. After annotating associated regions using GRAIL, expression quantitative trait loci data and correlations with non-synonymous SNPs, we identified many candidate genes that provide potentially important insights into disease pathogenesis, including IL1R2, IL8RA-IL8RB, IL7R, IL12B, DAP, PRDM1, JAK2, IRF5, GNA12 and LSP1. The total number of confirmed inflammatory bowel disease risk loci is now 99, including a minimum of 28 shared association signals between Crohn's disease and ulcerative colitis.

Precolostral serology in calves born from Neospora-seropositive mothers

The present study was designed to exploratively determine (a) how many healthy calves, born from seropositive mothers, were also precolostrally seropositive; (b) how many precolostrally negative calves became postcolostrally positive; and (c) in these calves, how the IgG1/IgG2 situation developed pre- and postcolostrally. All calves were born from mothers that were determined to be seropositive in a conventional Neospora caninum-ELISA and by immunoblotting. When the diagnostic performance of the conventional ELISA was compared with that of immunoblotting and an IgG1/IgG2-ELISA in the calves, the latter two exhibited a higher sensitivity: From a total of 15 precolostral calf sera, 7 were positive in the conventional ELISA (diagnostic sensitivity 47%) compared to 15 that were positive by immunoblotting (diagnostic sensitivity 100%) and 12 that were positive by the IgG1/IgG2-ELISA (diagnostic sensitivity 80%). With regard to IgG1/IgG2 findings in the dams, IgG2 appeared as the dominant subclass in the humoral immune response of adult cattle, while in calves, IgG1 appeared as the main prenatally/precolostrally reactive antibody isotype. Provided that precolostral seropositivity reflects postnatal persistent infection with N. caninum, we then postulate that, basically, all of our study calves born form N. caninum-seropositive mothers were prenatally infected with the parasite, and may, thus, all become members of the next transmitting generation.

Cyclooxygenase-2 inhibition selectively attenuates bone morphogenetic protein-6 synthesis and bone formation during guided tissue regeneration in a rat model

OBJECTIVES: Bone formation during guided tissue regeneration is a tightly regulated process involving cells, extracellular matrix and growth factors. The aims of this study were (i) to examine the expression of cyclooxygenase-2 (COX-2) during bone regeneration and (ii) the effects of selective COX-2 inhibition on osseous regeneration and growth factor expression in the rodent femur model. MATERIAL AND METHODS: A standardized transcortical defect of 5 x 1.5 mm was prepared in the femur of 12 male rats and a closed half-cylindrical titanium chamber was placed over the defect. The expression of COX-2 and of platelet-derived growth factor-B (PDGF-B), bone morphogenetic protein-6 (BMP-6) and insulin-like growth factor-I/II (IGF-I/II) was analyzed at Days 3, 7, 21 and 28 semiquantitatively by reverse transcriptase-polymerase chain reaction and immunohistochemistry. The effects of COX-2 inhibition by intraperitoneal injection of NS-398 (3 mg/kg/day) were analyzed in five additional animals sacrificed at Day 14. RESULTS: Histomorphometry revealed that new bone formation occurred in the cortical defect area as well as in the supracortical region, i.e. region within the chamber by Day 7 and increased through Day 28. Immunohistochemical evidence of COX-2 and PDGF-B levels were observed early (i.e. Day 3) and decreased rapidly by Day 7. BMP-6 expression was maximal at Day 3 and slowly declined by Day 28. In contrast, IGF-I/II expression gradually increased during the 28-day period. Systemic administration NS-398 caused a statistically significant reduction (P<0.05) in new bone formation (25-30%) and was associated with a statistically significant reduction in BMP-6 protein and mRNA expression (50% and 65% at P<0.05 and P<0.01, respectively). PDGF-B mRNA or protein expression was not affected by NS-398 treatment. CONCLUSION: COX-2 inhibition resulted in reduced BMP-6 expression and impaired osseous regeneration suggesting an important role for COX-2-induced signaling in BMP synthesis and new bone formation.

Do common genetic variants in endotoxin signaling pathway contribute to predisposition to alcoholic liver cirrhosis?

BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta), produced by endotoxin-activated Kupffer cells, play a key role in the pathogenesis of alcoholic liver cirrhosis (ALC). Alleles TNFA -238A, IL1B -31T and variant IL1RN*2 of repeat polymorphism in the gene encoding the IL-1 receptor antagonist increase production of TNF-alpha and IL-1beta, respectively. Alleles CD14 -159T, TLR4 c.896G and TLR4 c.1196T modify activation of Kupffer cells by endotoxin. We confirmed the published associations between these common variants and genetic predisposition to ALC by means of a large case-control association study conducted on two Central European populations. METHODS: The study population comprised a Czech sample of 198 ALC patients and 370 controls (MONICA project), and a German sample of 173 ALC patients and 331 controls (KORA-Augsburg), and 109 heavy drinkers without liver disease. RESULTS: Single locus analysis revealed no significant difference between patients and controls in all tested loci. Diplotype [IL1RN 2/ 2; IL1B -31T+] was associated with increased risk of ALC in the pilot study, but not in the validation samples. CONCLUSIONS: Although cytokine mediated immune reactions play a role in the pathogenesis of ALC, hereditary susceptibility caused by variants in the corresponding genes is low in Central European populations.