Impact of an Injectable Trace Mineral Supplement on the Immune Response and Outcome of Mannheimia haemolytica Infection in Feedlot Cattle.

The study aimed to assess the impact of injectable trace mineral ("ITM"; Multimin90; Fort Collins, CO) supplementation on bacterial infection in cattle. Angus-crossbred steers (n = 32) were organized into two blocks by initial body weight. Steers were maintained on a ryelage and dry-rolled corn-based growing diet without supplementation of Zn, Cu, Mn, and Se for the duration of the study. The steers were transported 6 h, then randomized into three treatment groups: control received sterile saline ("CON"), ITM administered 1 day after transport (6 days before infection, "ITMPRE"), and ITM administered 2 days post infection (dpi) concurrent with antibiotic treatment ("ITMPOST"). Steers were infected with Mannheimia haemolytica on day 0, and all were treated with tulathromycin at 2 dpi. Plasma levels of Zn, Cu, and Se did not differ among treatments (P ≥ 0.74). Liver Se was higher in ITMPRE at 2 dpi (P < 0.05), and both ITM groups had higher liver Se at 5 dpi (P < 0.05) compared to CON. A time × treatment interaction was detected for liver Cu (P = 0.02). Clinical scores were lower (P < 0.05) in ITMPRE on 1 and 8 dpi and ITMPOST on 8 dpi compared to CON. Thoracic ultrasonography scores were lower in ITMPRE at 2 dpi compared to CON (P < 0.05) and ITMPOST (P < 0.1). No treatment effects (P > 0.10) were observed for bacterial detection from bronchoalveolar lavage (BAL) or nasopharyngeal swabs. At 5 dpi, both ITMPRE and ITMPOST showed higher frequencies of γδ T cells and NK cells in BAL compared to CON (P < 0.05). Before infection, leukocytes from ITMPRE steers produced more IL-6 (P < 0.01) in response to stimulation with the TLR agonist, Pam3CSK4. Use of ITM may be an effective strategy for improving disease resistance in feedlot cattle facing health challenges.

Dietary Zinc Supplementation in Steers Modulates Labile Zinc Concentration and Zinc Transporter Gene Expression in Circulating Immune Cells.

Zinc (Zn) is critical for immune function, and marginal Zn deficiency in calves can lead to suboptimal growth and increased disease susceptibility. However, in contrast to other trace minerals such as copper, tissue concentrations of Zn do not change readily in conditions of supplementation or marginal deficiency. Therefore, the evaluation of Zn status remains challenging. Zinc transporters are essential for maintaining intracellular Zn homeostasis, and their expression may indicate changes in Zn status in the animal. Here, we investigated the effects of dietary Zn supplementation on labile Zn concentration and Zn transporter gene expression in circulating immune cells isolated from feedlot steers. Eighteen Angus crossbred steers (261 ± 14 kg) were blocked by body weight and randomly assigned to two dietary treatments: a control diet (58 mg Zn/kg DM, no supplemental Zn) or control plus 150 mg Zn/kg DM (HiZn; 207 mg Zn/kg DM total). After 33 days, Zn supplementation increased labile Zn concentrations (as FluoZin-3 fluorescence) in monocytes, granulocytes, and CD4 T cells (P < 0.05) but had the opposite effect on CD8 and γδ T cells (P < 0.05). Zn transporter gene expression was analyzed on purified immune cell populations collected on days 27 or 28. ZIP11 and ZnT1 gene expression was lower (P < 0.05) in CD4 T cells from HiZn compared to controls. Expression of ZIP6 in CD8 T cells (P = 0.02) and ZnT7 in B cells (P = 0.01) was upregulated in HiZn, while ZnT9 tended (P = 0.06) to increase in B cells from HiZn. These results suggest dietary Zn concentration affects both circulating immune cell Zn concentrations and Zn transporter gene expression in healthy steers.

Tropical high altitude and severe asthma in adults: house dust mite sensitization and phenotypic distribution.

BACKGROUND: There is a lack of information on house dust mite (HDM) sensitization and phenotype distribution in patients with severe asthma (SA) living permanently at high-altitude (HA) in tropical regions, which may be different. OBJECTIVE: The aim of this study was to characterize adults with SA in a tropical high altitude city (2,640 m): Bogotá, Colombia. MATERIAL AND METHODS: This observational cross-sectional study included severe asthmatic outpatients (n = 129) referred to the ASMAIRE program of the Fundación Neumológica Colombiana in Bogotá (2,640 m). Clinical history, spirometry, total IgE, blood eosinophils, and skin prick test (SPT), including HDM allergens, were performed. Phenotype definitions: Allergic/atopic (AA): IgE ≥100 IU/mL and/or at least one positive SPT; eosinophilic (EOS): blood eosinophils ≥300 cells/µL; type 2-high: AA and/or EOS phenotype; type 2-low: non-AA/non-EOS phenotype (IgE <100 IU/mL, negative SPT, and blood eosinophils <300 cells/µL). RESULTS: A total of 129 adults with SA were included, 79.8% female. Phenotype distribution: AA: 61.2%; EOS: 37.2%; type 2-high: 72.1%; type 2-low: 27.9%. Among AA patients, HDM sensitization was present in 87% and 34.9% were non-eosinophilic. There was a significant overlap between the phenotypes. CONCLUSIONS: In contrast to non-tropical high-altitude regions, we found a high frequency of HDM sensitization in patients with AA phenotype living in a tropical high-altitude city. We also found a discrete lower frequency of EOS phenotype with no other significant differences in the phenotypic distribution compared to that described at low altitudes. We propose that tropical location may modify the effect of high altitude on HDM concentrations and allergenicity.

Prospective study of percutaneous radiofrequency sympathicolysis in severe hyperhidrosis and facial blushing: efficacy and safety findings.

OBJECTIVE: Hyperhidrosis (Hh) and facial blushing (Fb) are conditions caused by hyperactivity of the sympathetic system; they affect around 2% of the population. Severe cases have been typically treated with thoracic sympathectomy through a minimally invasive approach. We sought to determine if severe Hh and/or Fb patients, who are reluctant to go through an operation with general anaesthesia, could benefit from receiving percutaneous radiofrequency ablation of the sympathetic chain. METHODS: Prospectively collected data obtained from May 2007 to May 2010 were analysed to compare the treatment efficacy and effects on quality of life of the two procedures. RESULTS: From a total of 58 patients enrolled in the study, 31 were treated with radiofrequency procedures, whereas 27 received surgical sympathectomy. Patients with Hh had better results with surgery than with radiofrequency sympathicolysis in terms of efficacy (p=0.0001) and quality of life (p=0.0002). However, there was still a significant improvement in quality of life in the group of patients treated with radiofrequency sympathicolysis (p=0.004). Patients with Fb had good results with surgical procedures and poor outcomes with radiofrequency ablation, resulting in significant differences in treatment efficacy (p=0.005) and in quality of life (p=0.003). Fb patients treated with radiofrequency procedures had no improvement in quality of life after the intervention (p=0.28). CONCLUSION: Our results support the view of surgical sympathectomy as the gold-standard treatment in severe cases of Hh and Fb. Radiofrequency sympathicolysis is useful as a second-treatment choice for Hh patients. Fb patients do not benefit from radiofrequency sympathicolysis.

Inhibitor of differentiation-1 as a novel prognostic factor in NSCLC patients with adenocarcinoma histology and its potential contribution to therapy resistance.

PURPOSE: High inhibitor of differentiation-1 (Id1) levels have been found in some tumor types. We aimed to study Id1 levels and their prognostic impact in a large series of stages I to IV non-small cell lung cancer (NSCLC) patients. Experiments in cell lines and cells derived from malignant pleural effusions (MPE) were also carried out. EXPERIMENTAL DESIGN: A total of 346 NSCLC samples (three different cohorts), including 65 matched nonmalignant tissues, were evaluated for Id1 expression by using immunohistochemistry. Additional data from a fourth cohort including 111 patients were obtained for Id1 mRNA expression analysis by using publicly available microarrays. In vitro proliferation assays were conducted to characterize the impact of Id1 on growth and treatment sensitivity. RESULTS: Significantly higher Id1 protein levels were found in tumors compared with normal tissues (P < 0.001) and in squamous carcinomas compared with adenocarcinomas (P < 0.001). In radically treated stages I to III patients and stage IV patients treated with chemotherapy, higher Id1 levels were associated with a shorter disease-free survival and overall survival in adenocarcinoma patients in a log-rank test. A Cox model confirmed the independent prognostic value of Id1 levels for both stages I to III and stage IV patients. In silico analysis confirmed a correlation between higher Id1 mRNA levels and poor prognosis for adenocarcinoma subjects. In vitro Id1 silencing in radio/chemotherapy-resistant adenocarcinoma cells from MPEs restored sensitivity to both therapies. CONCLUSIONS: In our series, Id1 levels showed an independent prognostic value in patients with adenocarcinoma, regardless of the stage. Id1 silencing may sensitize adenocarcinoma cells to radiotherapy and chemotherapy.

Hipertensión pulmonar en la enfermedad pulmonar obstructiva crónica / Pulmonary hypertension in chronic obstructive pulmonary disease

La hipertensión pulmonar (HP) es una complicación relativamente frecuente de la enfermedad pulmonar obstructiva crónica (EPOC). Su aparición en el curso clínico de la EPOC es un factor condicionante de peor pronóstico que se asocia con disminución de la sobrevida y mayor uso de recursos de salud. Aunque no hay una relación lineal bien definida, la prevalencia de HP en pacientes con EPOC aumenta a medida que es mayor el grado de obstrucción y la severidad de la enfermedad, siendo poco frecuente en casos de EPOC leve y moderada. La HP en la EPOC es, en general, leve o moderada y pocas veces afecta la función ventricular derecha. En muchos casos no es aparente en reposo y se manifiesta con el ejercicio. La HP puede llegar a ser severa o estar "fuera de proporción" para el grado de severidad de la EPOC. En esta situación debe explorarse la posibilidad de condiciones asociadas, si bien, con frecuencia, la única explicación final sea la EPOC. Poco se sabe de la prevalencia y el comportamiento de la HP en pacientes con EPOC residentes en alturas intermedias y grandes (>2.500 metros sobre el nivel del mar) que es una situación frecuente en Latinoamérica y Asia. La HP en EPOC no está relacionada exclusivamente con la hipoxia/hipoxemia y la hipercapnia. Los trastornos mecánicos propios de la EPOC (hiperinflación y presión alveolar) y la inflamación pueden prevalecer como causa de la lesión endotelial y la remodelación de la circulación pulmonar contribuyentes al aumento de la presión y la resistencia vascular pulmonar. La aparición de signos de cor pulmonale indica una condición avanzada de la HP, por lo cual esta condición debe sospecharse tempranamente cuando la disnea, la hipoxemia y el deterioro de la difusión son desproporcionados para el grado de obstrucción. La confirmación de la HP se hace mediante ecocardiografía doppler y el cateterismo derecho sólo se justifica en casos individualizados. La terapia a largo plazo con oxígeno es la única intervención que ha mostrado ser eficaz temporalmente. Los vasodilatadores convencionales no producen mejoría a mediano y largo plazo y pueden empeorar las relaciones ventilación-perfusión. De la misma forma, las nuevas terapias para HP no parecen ser una opción terapéutica salvo en los casos de "HP fuera de proporción" en los cuales otros factores diferentes de la EPOC podrían estar presentes. El desconocimiento del comportamiento de la HP en pacientes con EPOC residentes en alturas intermedias y grandes abre también un campo de investigación en el papel de las terapias con oxígeno y farmacológica en estas alturas.

Long-term results after resection for bone sarcoma pulmonary metastases.

BACKGROUND: Pulmonary metastases from bone sarcomas occur in approximately 40% of the cases. The combination of both chemotherapy and surgical resection is currently the standard treatment options for these patients. We aim to study the influence of different prognostic factors on long-term survival. METHODS: We reviewed the prognostic factors and survival rate in 52 consecutive patients with pulmonary metastases from bone sarcomas. All of them were previously treated with chemotherapy and submitted to metastasectomy at our institution from 1996 to 2006. Clinical and demographic variables, related to the primary tumour as well as to the pulmonary metastases, and treatment procedures were registered. Univariate (log-rank) and multivariate (Cox regression) analysis were carried out to identify significant prognostic factors related to overall survival. Five-year survival rates were estimated using Kaplan-Meier methods. RESULTS: Median follow-up was 28 months. Follow-up duration ranged 7-148 months; the median survival was 27 months. As many as 31% of the patients were alive without disease, 3% were alive with disease, 64% died of disease while 2% died from other causes. Complete resection was achieved in 49 cases (94%). The overall 3- and 5-year survival rates were 43% and 31%, respectively. Univariate analysis showed (1) disease-free interval between treatment of the primary bone tumour and first lung metastasectomy (DFI) and (2) disease-free interval between first and second lung surgery (DFI2) as prognostic factors. Gender, primary site, histology of primary tumour, surgical approach, number of lung nodules, type of lung resection and re-do lung surgery did not have a significant impact on survival. CONCLUSION: The long-term survival after bone sarcoma lung metastasectomy is encouraging. In our series, DFI and DFI2 were identified as the only prognostic factors.

Long-term results after resection for soft tissue sarcoma pulmonary metastases.

Isolated pulmonary metastases from soft tissue sarcomas (STS) occur in approximately 20% of the cases. Chemotherapy and surgical resection are the current standard treatment options for these patients. Our goal was to identify any prognostic factors for these patients as well as to estimate their long-term survival rate. We examined a series of twenty-two consecutive patients with pulmonary metastases from STS, treated in our institution from 1996 to 2006. Univariate (log-rank and Cox-regression) analysis was performed to identify any significant prognostic factor. Five-year survival rates were estimated by using Kaplan-Meier methods. Four patients (18.2%) were alive without any disease, twelve patients (54.5%) died of disease and we lost all track of six patients (27.3%). Follow-up period ranged from 7 to 75 months. Median follow-up: 14 months, median survival: 19 months. Disease-free interval (DFI) (P=0.005), number of lung nodules (P=0.04) and histology type (P=0.01) were significant prognostic factors at univariate analysis. The overall five-year survival rate was 23.1%. DFI, number of lung nodules at surgery and metastatic histology are significant prognostic factors for patients with resected pulmonary metastases from STS.