The prognostic value of cerebrospinal fluid characteristics in dogs without deep pain perception due to thoracolumbar disc herniation.

Providing a pre-operative prognosis for dogs presented with absent deep pain perception (DPP) is extremely challenging, as the overall recovery rates widely vary. This study assesses the possible correlation between the severity of spinal cord injury and CSF cytology in 31 paraplegic dogs presented with absent DPP due to acute thoracolumbar intervertebral disc herniation (TL-IVDH). All dogs underwent surgical decompression immediately following diagnosis. CSF TNCC, macrophage percentage and macrophage to monocyte (MΦ:M) ratio were significantly higher in dogs that failed to regain DPP within 10 days post-operatively and in dogs that failed to regain ambulation at the end of the study period (P< 0.05). MΦ:M of 0.73 and higher corresponded to a sensitivity of 54% and specificity of 100% for prediction of a negative long-term outcome. CSF TNCC, macrophage percentage and MΦ:M ratio effectively predicted regaining DPP and the long-term outcome in dogs that lost DPP due to acute TL-IVDH.

Tumor necrosis factor-α and interleukin-6 concentrations in cerebrospinal fluid of dogs after seizures.

BACKGROUND: Idiopathic and acquired epilepsy are common in dogs. Up to 30% of these dogs are refractory to pharmacological treatment. Accumulating experimental evidence indicates that brain immune response and presence of inflammatory mediators decrease the threshold for individual seizures and contribute to epileptogenesis. HYPOTHESIS: Dogs with seizures have higher cerebrospinal interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) concentrations compared to dogs with no seizures. METHODS: A prospective double blinded study; cerebrospinal fluid (CSF) and serum IL-6, TNF-α and total protein (TP) concentrations were measured by a blinded investigator for the study group and CSF IL-6 and TNF-α levels and TP concentrations were measured in the control group (CG). ANIMALS: Dogs presented with seizures that had enough CSF collected to allow analysis were included in the study group. Twelve apparently healthy, quarantined, stray dogs served as control (CG). RESULTS: Cerebrospinal fluid TNF-α and IL-6 concentrations were significantly higher (P = .011, P = .039) in dogs with seizures (0 ± 70.66, 0.65 ± 10.93 pg/mL) compared to the CG (0 ± 19, 0.73 ± 0.55 pg/mL). When assessing cytokine concentrations of specifically the idiopathic epilepsy (IE) dogs compared to the CG, only TNF-α concentrations (8.66 ± 62, 0 ± 19 pg/mL) were significantly higher (P = .01). CSF TP concentrations were not significantly higher in the study dogs compared to the CG. CONCLUSIONS AND CLINICAL IMPORTANCE: Higher TNF-α and IL-6 concentration in the CSF of dogs with naturally occurring seizures. The higher supports the hypothesis that inflammatory processes through certain mediators play a role in the pathogenesis of seizures in dogs.

Antigen-chip technology for accessing global information about the state of the body.

Traditionally, immunologic diagnosis has been based on an attempt to correlate each disease with a specific immune reactivity, such as an antibody or a T-cell response to a single antigen specific for the disease entity. The state of the body, however, appears to be encoded by the immune system in collectives of reactivities and not by single reactivities. Here we describe our use of microarray technology and informatics to develop an antigen chip capable of detecting global patterns of antibodies binding to hundreds of antigens simultaneously. The patterns fashion diagnostic signatures.

Why do young women smoke? I. Direct and interactive effects of environment, psychological characteristics and nicotinic cholinergic receptor genes.

Despite the health hazards, cigarette smoking is disproportionately frequent among young women. A significant contribution of genetic factors to smoking phenotypes is well established. Efforts to identify susceptibility genes do not generally take into account possible interaction with environment, life experience and psychological characteristics. We recruited 501 female Israeli students aged 20-30 years, obtained comprehensive background data and details of cigarette smoking and administered a battery of psychological instruments. Smoking initiators (n=242) were divided into subgroups with high (n=127) and low (n=115) levels of nicotine dependence based on their scores on the Fagerstrom Tolerance Questionnaire and genotyped with noninitiators (n=142) for single nucleotide polymorphisms (SNPs) in 11 nicotinic cholinergic receptor genes. We found nominally significant (P<0.05) allelic and genotypic association with smoking initiation of SNP rs2072660 and multilocus haplotypes (P<0.007-0.05) in CHRNB2 and nominal (P<0.05) allelic or genotypic association of SNPs in CHRNA7 (rs1909884), CHRNA9 (rs4861065) and CHRNB3 (rs9298629) with nicotine dependence. Employing logistic regression and controlling for known risk factors, the best-fitting model for smoking initiation encompassed a 5 SNP haplotype in CHRNB2, neuroticism and novelty seeking (P=5.9 x 10(-14), Nagelkerke r(2)=0.30). For severity of nicotine dependence, two SNPs in CHRNA7 (rs1909884 and rs883473), one SNP in CHRNA5 (rs680244) and the interaction of a SNP in CHRNA7 (rs2337980) with neuroticism, were included in the model (P=2.24 x 10(-7), Nagelkerke r(2)=0.40). These findings indicate that background factors, psychological characteristics and genetic variation in nicotinic cholinergic receptors contribute independently or interactively to smoking initiation and to severity of nicotine dependence in young women.

Vessel maturation effects on tumour growth: validation of a computer model in implanted human ovarian carcinoma spheroids.

We analysed measurements of tumour growth, neovascular maturation and function in human epithelial ovarian carcinoma xenografts, studied noninvasively by magnetic resonance imaging. Results suggest that vascular maturation and mature and immature vessel regression occur continuously during tumour neovascularisation. Moreover, in these spheroids, a high tumour growth-rate is associated with monotonic changes in vessel density (VD) and with large proportions of mature blood vessels, whereas a lower tumour growth-rate is associated with fluctuating VD and lower proportions of mature vessels. These results corroborate a mathematical model for tumour dynamics, including vascular maturation and immature and mature vessel regression. The model predicts that rapid tumour growth may result from a high maturation-rate of neo-vasculatures, due to substantial mature VD in the microenvironment, while a slower tumour growth is an outcome of a lower background VD, leading to a lower vessel maturation-rate, larger proportion of immature vessels and, consequently, to regression-driven instabilities. The generality of these results for other tumour types should be validated.