Progressive atrophic rhinitis is an upper respiratory tract disease of pigs caused by toxigenic strains of the bacterium Pasteurella multocida. In this study the effect of P. multocida on the humoral immune response of pigs and mice was investigated. Pigs were given live intranasal challenge with either a toxigenic strain or a non-toxigenic strain of P. multocida, or were given daily intranasal instillation of a cell-free lysate of the toxigenic strain. Mice were given a live intranasal challenge of either a toxigenic or a non-toxigenic strain of P. multocida. All of the animals were immunised with ovalbumin and serum concentrations of anti-ovalbumin antibodies were quantified and compared between different treatment groups and control animals. Intranasal challenge with toxigenic P. multocida caused a significant reduction in the levels of anti-ovalbumin IgG in both species. A similar effect was seen in pigs given a cell-free extract of toxigenic P. multocida. Whilst the mechanism of this suppression is unclear, we surmise that immunomodulation of the host is an important virulence factor for toxigenic P. multocida, and could be an important function of the toxin. This immunomodulatory effect may enhance colonisation of P. multocida aiding horizontal transmission and may predispose to concurrent infection with other potential pathogens.
Summary: Interleukin-2 (IL-2) and a-interferon have each shown antitumor activity in patients with disseminated malignant melanoma. Because animal studies suggest enhanced activity for the combination over each agent used alone, this trial using a relatively low-dose outpatient regimen was undertaken. IL-2 at a dose of 2 x 106 U/m2/day (Roche units) was given by continuous intravenous infusion for 4 days a week with interferon-α-2a at a dose of 6 x 106 U/m2/day given by s.c. or i.m. injection on days 1 and 4 of each treatment week. One cycle consisted of 4 consecutive weeks of treatment followed by a 2-week rest period. Fourteen patients were entered in this study. No complete or partial responses were seen. One patient required dose reduction because of grade 3 diarrhea and two patients had interruption of treatment because of central-line-related sepsis. Fatigue was common in all patients. This low-dose combination regimen of IL-2 and a-interferon does not appear to be better than the single agents used alone in optimal dosage.
To cite this article: Lewis MC, Inman CF, Patel D, Schmidt B, Mulder I, Miller B, Gill BP, Pluske J, Kelly D, Stokes CR, Bailey M. Direct experimental evidence that early‐life farm environment influences regulation of immune responses. Pediatr Allergy Immunol 2012: 23 : 265–269. Abstract Background: In mammals, early‐life environmental variations appear to affect microbial colonization and therefore competent immune development, and exposure to farm environments in infants has been inversely correlated with allergy development. Modelling these effects using manipulation of neonatal rodents is difficult due to their dependency on the mother, but the relatively independent piglet is increasingly identified as a valuable translational model for humans. This study was designed to correlate immune regulation in piglets with early‐life environment. Methods: Piglets were nursed by their mother on a commercial farm, while isolator‐reared siblings were formula fed. Fluorescence immunohistology was used to quantify T‐reg and effector T‐cell populations in the intestinal lamina propria and the systemic response to food proteins was quantified by capture ELISA. Results: There was more CD4 + and CD4 + CD25 + effector T‐cell staining in the intestinal mucosa of the isolator‐reared piglets compared with their farm‐reared counterparts. In contrast, these isolator‐reared piglets had a significantly reduced CD4 + CD25 + Foxp3 + regulatory T‐cell population compared to farm‐reared littermates, resulting in a significantly higher T‐reg‐to‐effector ratio in the farm animals. Consistent with these findings, isolator‐reared piglets had an increased serum IgG anti‐soya response to novel dietary soya protein relative to farm‐reared piglets. Conclusion: Here, we provide the first direct evidence, derived from intervention, that components of the early‐life environment present on farms profoundly affects both local development of regulatory components of the mucosal immune system and immune responses to food proteins at weaning. We propose that neonatal piglets provide a tractable model which allows maternal and treatment effects to be statistically separated.
Aggressive non-Hodgkin's lymphoma (aNHL) is associated with poor long-term survival after relapse, and treatment is limited by a lack of consensus regarding standard of care. Pixantrone was studied in a randomized trial in patients with relapsed or refractory aNHL who had failed ≥ 2 lines of therapy, demonstrating a significant improvement in complete or unconfirmed complete response and progression-free survival (PFS) compared with investigators' choice of single-agent therapy. The objective of this study was to assess the health economic implications of pixantrone versus current clinical practice (CCP) in the United Kingdom for patients with multiply relapsed or refractory aNHL receiving their third or fourth line of treatment.A semi-Markov partition model based on overall survival and PFS was developed to evaluate the lifetime clinical and economic impact of treatment of multiply relapsed or refractory aNHL with pixantrone versus CCP. The empirical overall survival and PFS data from the PIX301 trial were extrapolated to a lifetime horizon. Resource use was elicited from clinical experts, and unit costs and utilities were obtained from published sources. The analysis was conducted from the perspective of the United Kingdom's National Health Service and personal social services. Outcomes evaluated were total costs, life-years, quality-adjusted life-years (QALYs), and cost per QALY gained. Deterministic and probabilistic sensitivity analyses were conducted to assess uncertainty around the results.Pixantrone was estimated to increase life expectancy by a mean of 10.8 months per patient compared with CCP and a mean gain of 0.56 discounted QALYs. The increased health gains were associated with an increase in discounted costs of approximately £18,494 per patient. The incremental cost-effectiveness ratio of pixantrone versus CCP was £33,272 per QALY gained. Sensitivity and scenario analyses suggest that the incremental cost-effectiveness ratio was sensitive to uncertainty in the PFS and overall survival estimates and the utility values associated with each health state.Pixantrone may be considered both clinically effective and cost-effective for patients with multiply relapsed or refractory aNHL who currently have a high level of unmet need.
Abstract: Hypertension has been well recognized as a major contributor of chronic cardiovascular disease, resulting in significant morbidity and mortality not only in adults but also in children and adolescents. Primary or essential hypertension refers to cases where no underlying etiology is apparent for the high blood pressure, and accounts for a majority of the patients. Secondary hypertension refers to a much smaller group of patients in whom the blood pressure elevation may be attributed to an underlying cause. With improved diagnostic techniques, some cases of previously diagnosed essential hypertension may be found to have an underlying etiology. Endocrine causes account for a relatively small proportion of all patients with hypertension. In the following discussion, only secondary hypertension due to endocrine-related causes will be discussed. Keywords: primary hyperalsosteronism, paraganglioma, beta-hydroxy-steroid dehydogenase deficiency, Liddle syndrome, Gordon syndrome
The pathogenicity of Enterotoxigenic Escherichia coli (ETEC) expressing F4ac (K88) fimbrial adhesin and its adhesion to the pig jejunum surface is genetically controlled by the presence of a specific receptor glycoprotein on brush borders of the epithelium. We firstly screened the degree of inhibition obtained with ten galactose-recognising lectins – respectively from Abrus precatorius (APA-I); Coregonus maraena; Euphorbia characias; Crotalaria juncea; Sambucus ebulus (SEL1d); Sambucus nigra (SNAV); Coregonus peled; Momordica charantia (MCL); Trychosanthes kirilowii; Adenia racemosa –, by an ELISA test based on intestinal brush border sensitive for E. coli F4ac adhesion and ETEC F4ac fimbrial antigen. Three lectins significantly inhibited the fimbrial adhesion and the highest value was obtained by Crotalaria juncea lectin (p < .01). The results were then confirmed by an in vitro inhibition test of ETEC adhesion to villi isolated from ETEC susceptible pigs. The favourable results obtained with the supplementation of two d-galactose lectins against the ETEC adhesion to intestinal villi stimulate in vivo testing of the addition of these lectins in the piglet feeding
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