Retrospective study investigating causes of abnormal respiratory noise in horses following prosthetic laryngoplasty.

REASONS FOR PERFORMING THE STUDY: To investigate causes of respiratory noises in horses following prosthetic laryngoplasty (with or without a ventriculocordectomy) and to examine potential associations between degree of arytenoid abduction and the presence of other upper respiratory tract (URT) abnormalities, including right-sided collapse. METHODS: Clinical records and dynamic videoendoscopic recordings were examined from horses presented between 1995 and 2010 for investigation of respiratory noise during exercise, following a prosthetic laryngoplasty (+/- a ventriculocordectomy). Relationships between the degree of left arytenoid cartilage abduction and the presence of other URT disorders were investigated. RESULTS: Thirty horses matched the inclusion criteria. All horses had previously undergone a prosthetic laryngoplasty in different hospitals and in 63% (19/30) of these horses a left-sided ventriculocordectomy had also been performed. The majority of cases (87%) had multiple respiratory abnormalities and only 13% had a single URT disorder. Palatal dysfunction was the most common diagnosis (83%), followed by axial deviation of the aryepiglottic folds (60%) and vocal cord collapse (43%). The right arytenoid cartilage was fully abducted in all cases and no statistically significant correlation between the degree of left arytenoid abduction and any other URT disorders was detected. CONCLUSIONS: Multiple forms of dynamic URT disorders were diagnosed in horses that presented with abnormal respiratory noise following laryngoplasty. There was no association between degree of left arytenoid abduction and other URT abnormalities. Furthermore, horses with suboptimal left arytenoid cartilage abduction were not predisposed to right-sided laryngeal collapse. CLINICAL RELEVANCE: Our results demonstrate the fundamental role of dynamic endoscopy in correctly diagnosing dynamic airway collapse in horses that have undergone surgical treatment of the upper respiratory tract.

Distribution of radiodense contrast medium after perineural injection of the palmar and palmar metacarpal nerves (low 4-point nerve block): an in vivo and ex vivo study in horses.

REASONS FOR PERFORMING STUDY: Evidence-based information is limited on distribution of local anaesthetic solution following perineural analgesia of the palmar (Pa) and palmar metacarpal (PaM) nerves in the distal aspect of the metacarpal (Mc) region ('low 4-point nerve block'). OBJECTIVES: To demonstrate the potential distribution of local anaesthetic solution after a low 4-point nerve block using a radiographic contrast model. METHODS: A radiodense contrast medium was injected subcutaneously over the medial or the lateral Pa nerve at the junction of the proximal three-quarters and distal quarter of the Mc region (Pa injection) and over the ipsilateral PaM nerve immediately distal to the distal aspect of the second or fourth Mc bones (PaM injection) in both forelimbs of 10 mature horses free from lameness. Radiographs were obtained 0, 10 and 20 min after injection and analysed subjectively and objectively. Methylene blue and a radiodense contrast medium were injected in 20 cadaver limbs using the same techniques. Radiographs were obtained and the limbs dissected. RESULTS: After 31/40 (77.5%) Pa injections, the pattern of the contrast medium suggested distribution in the neurovascular bundle. There was significant proximal diffusion with time, but the main contrast medium patch never progressed proximal to the mid-Mc region. The radiological appearance of 2 limbs suggested that contrast medium was present in the digital flexor tendon sheath (DFTS). After PaM injections, the contrast medium was distributed diffusely around the injection site in the majority of the limbs. In cadaver limbs, after Pa injections, the contrast medium and the dye were distributed in the neurovascular bundle in 8/20 (40%) limbs and in the DFTS in 6/20 (30%) of limbs. After PaM injections, the contrast and dye were distributed diffusely around the injection site in 9/20 (45%) limbs and showed diffuse and tubular distribution in 11/20 (55%) limbs. CONCLUSIONS AND POTENTIAL RELEVANCE: Proximal diffusion of local anaesthetic solution after a low 4-point nerve block is unlikely to be responsible for decreasing lameness caused by pain in the proximal Mc region. The DFTS may be penetrated inadvertently when performing a low 4-point nerve block.

HCV screening to enable early treatment of hepatitis C: a mathematical model to analyse costs and outcomes in two populations.

Early treatment of acute hepatitis C virus (HCV) infections reflects a new clinical paradigm and a significant option to reduce the socioeconomic burden of HCV. Therefore, this approach seems suitable as a new strategy to face HCV and prevent end stage liver diseases and premature deaths due to progressed chronic HCV-infections. The main limitation of this approach is that the majority of acute infections show an asymptomatic course and do thus not present to the health-care settings. Screening for HCV has already been extensively studied in the literature. This paper offers further insights in screening for HCV using cost effectiveness analysis for the impact of screening in two cohorts: Injecting Drug Users (IDUs) and Individuals With Surgery (IWSs). The setting of the cost effectiveness simulation is the Veneto Region in the North-east of Italy. Using a Markov model of the natural history of HCV infection we derive costs, quality-adjusted life years (QALYs) and incremental cost-effectiveness related to screening vs. no-screening strategies. In the IDUs cohort, the screening strategy can result in a substantial difference in premature deaths and dominates (less costs better outcomes) the no-screening one. The overall outcomes of the screening strategy are mostly affected by the prevalence of HCV and of genotypes that are more relatively more difficult to treat (above 10% of prevalence for its cost effectiveness). The number of premature deaths prevented in the IWSs cohort is lower and there seems to be an unacceptable incremental cost per QALY gained, which may be unsustainable for society.

The societal burden of HIV/AIDS in Northern Italy: an analysis of costs and quality of life.

This study aims to measure the direct and indirect costs of HIV/AIDS care and quality of life (QoL) of HIV-infected patients in Northern Italy. We conducted a prospective cohort study over 12 months, enrolling a sample of 121 patients with HIV infection from two cities in Northern Italy. Patients were surveyed at baseline and were followed-up at 6 and 12 months. To assess the relationship between costs and stage of disease, patients were categorized into three groups at baseline: "No HAART" (asymptomatic and never before on highly active antiretroviral therapy (HAART)), "Stable HAART" (HAART with mild HIV infection and no prior opportunistic infections) and "HAART failure" (primary HAART regimen was altered because of severe side effects or immunological failure). Direct medical costs were based on utilization of (day) hospital admissions, diagnostic procedures, laboratory tests, clinic visits, consultations and antiretroviral drug use. Indirect costs included production losses due to absence from work, reduced productivity at work and reduced unpaid labour participation. QoL was assessed by visual analogue scale. Parametric regression was used to estimate the expected value and the standard deviation of annual costs per patient. The expected value of total annual costs was 1818 euros and 9820 euros and 12,332 euros, for groups "No HAART", "Stable HAART" and "HAART failure" respectively. We estimated annual expected earnings as 14,994 euros and 10,811 euros and 9820 euros for the same respective groups. The expected value of QoL on a scale of 0-1 in these same patient groups was 0.80, 0.78 and 0.64. We conclude that indirect costs contribute substantially to total costs and are comparable in magnitude to the direct costs excluding antiretroviral drugs. The costs of inpatient care in our cohort were almost negligible compared to total costs. Despite being in treatment, many patients were still gainfully employed and generated substantial expected annual earnings.

Diesters of glycosylglycerols active in cancer chemoprevention.

Enzymatic transesterification, mediated by Pseudomonas cepacia lipase (lipase PS), led to the pure 1,6'-diacylderivatives of 2-O-beta-D-glucosyl-sn-glycerol and 2-O-beta-D-galactosyl-sn-glycerol, the acyl chains being derived from short-medium length fatty acids. A study of the in vitro inhibitory effects of these diacylderivatives on Epstein-Barr virus early antigen activation induced by the tumour promoter 12-O-tetradecanoylphorbol-13-acetate revealed that maximum activity was reached for the hexanoyl chain and that the introduction of a second acyl chain did not significantly modify the inhibitory potential referring to the corresponding 1- or 6'-monoesters.

Anti-tumor-promoting effects of glycoglycerolipid analogues on two-stage mouse skin carcinogenesis.

Four glycoglycerolipid analogues, 1-O-hexanoyl-2-O-beta-D-glucopyranosyl-sn-glycerol (1), 1-O-hexanoyl-2-O-beta-D-galactopyranosyl-sn-glycerol (2), 2-O-(6-O-hexanoyl-beta-D-galactopyranosyl)-sn-glycerol (3) and 2-O-(6-O-hexanoyl-alpha-D-galactopyranosyl)-sn-glycerol (4), potent in vitro inhibitors of 12-O-tetradecanoylphorbol-13-acetate (TPA) induced Epstein-Barr virus early antigen (EBV-EA) activation, were submitted to an in vivo two-stage mouse skin carcinogenesis test, using dimethylbenz[a]anthracene (DMBA) and TPA. The study was extended to two deacylated galactosylglycerol structures, 1-O-beta-D-galactopyranosyl-sn-glycerol (5) and 3-O-beta-D-galactopyranosyl-sn-glycerol (6). All the tested compounds exhibited remarkable anti-tumor-promoting effects on mouse skin tumor promotion, the 1-hexanoate 2 being the most active among the glycoglycerolipids until now studied.

Glycoglycerolipid analogues active as anti-tumor-promoters: the influence of the anomeric configuration.

The in vitro anti-tumor promoting effect of monohexanoates of 2-O-alpha-D-gluco- and galactopyranosyl-sn-glycerol on the 12-O-tetradecanoylphorbol-13-acetate (TPA) induced Epstein-Barr virus early antigen (EBV-EA) activation was evaluated and compared to the potencies of the corresponding beta-anomers. The results show that the inversion of the anomeric configuration from beta to alpha does not seem to significantly influence the activity, which is present, as for the beta-anomers, even at 1x10 mol ratio without any cytotoxicity.

Chemoenzymatic synthesis and antitumor promoting activity of 6'- and 3-esters of 2-O-beta-D-glucosylglycerol.

Through a simple chemoenzymatic approach 6'- and 3-esters of 2-O-beta-D-glucosylglycerol 1, with short-medium length fatty acid acyl chains, were prepared. The study of their in vitro antitumor promoting effect on Epstein-Barr virus early antigen (EBV-EA) activation, in comparison with that of the 1-esters previously described, confirms the significant activity of such monoacylated glycoglycerolipid analogues and establishes for the glucose series that the 1-substitution and the hexanoyl chain are the proper structural features for the maximum activity.

Inhibitory effects of monoacylated 2-O-beta-galactosylglycerols on Epstein-Barr virus activation: the significant role of the hexanoyl chain.

Three series of monoacyl-2-O-beta-D-galactosylglycerols bearing an acyl chain of varying length, from C4 to C10, were studied due to their antitumor promoting effects on the activation of the Epstein-Barr virus early antigen (EBV-EA), such activation being induced by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). This study indicates that it is more the length of the acyl chain that is important for the activity, six carbon atoms resulting in maximum effect, rather than the position of the ester function and the nature of the sugar (galactose or glucose).