Discrete subaortic stenosis in Newfoundland dogs: association of infective endocarditis

Necropsy findings are described in eight Newfoundland dogs from the same colony with discrete subaortic stenosis. Infective endocarditis involving the aortic valve occurred in four dogs and in each it proved fatal. Damage to the aortic valve cusps by the jet of blood ejected through the discretely narrowed left ventricular outflow tract predisposes to the development of infective endocarditis in both dogs and human beings with discrete subaortic stenosis. Severe abnormality of the intramural coronary arteries in the ventricular septum, which also occurs in patients with hypertrophic cardiomyopathy, was present in all eight dogs. Myocardial fiber disorganization and asymmetric septal hypertrophy, two other findings observed in patients with hypertrophic cardiomyopathy, were absent in each of the eight Newfoundland dogs with discrete subaortic stenosis.     

Differential behavioral effects of ACTH 4–10 and [D-Phe7]ACTH 4–10

Intraventricular administration of an access of ACTH 4–10 does not interfere with the excessive grooming behavior of rats, elicited by intraventricular administration of [D-Phe⁷ ]ACTH 4–10. In an avoidance extinction paradigm, the two ACTH analogs have opposite effects. ACTH 4–10 counteracts the facilitation of extinction seen after [D-Phe⁷]ACTH 4–10, only under conditions that treatment with ACTH 4–10 alone results in retardation of that extinction. The data are discussed in terms of a multiple interaction of these peptides with brain function.     

Involvement of rostral prefrontal cortex in selection between stimulus-oriented and stimulus-independent thought

We used functional magnetic resonance imaging to investigate brain activity while healthy subjects performed three different tasks, each of which alternated between: (i) phases relying on stimulus-oriented thought (i.e. cognitive processes provoked by incoming sensory information); and (ii) phases relying on stimulus-independent thought (i.e. cognitive processes that were not related to any information in the immediate sensory environment). Within each task, the two phases were matched as closely as possible. In all three tasks, lateral rostral prefrontal cortex was transiently activated by a switch between stimulus-oriented and stimulus-independent thought (regardless of the direction of the switch). Medial rostral prefrontal cortex consistently exhibited sustained activity for stimulus-oriented vs. stimulus-independent thought. These results suggest the involvement of rostral prefrontal cortex in selection between stimulus-oriented and stimulus-independent cognitive processes.     

Inflammatory profile in nasal secretions of infants hospitalized with acute lower airway tract infections

OBJECTIVE: The aim of this study was to determine whether the regulatory immune response (interleukin (IL)-10 response) differed between children hospitalized with acute respiratory infections and wheezing. METHODOLOGY: Infants with signs and symptoms of acute viral respiratory infection, admitted during winter 2000 to Princess Margaret Hospital for Children, Perth, WA, Australia, were enrolled in this study. Nasopharyngeal aspirates were collected in the first 48 h of admission. Total cell count and differential cell counts were assessed. Samples were tested for the presence of respiratory viruses. The concentrations of the anti-inflammatory cytokine IL-10, and pro-inflammatory cytokines IL-8, interferon-gamma, and IL-11 were determined by ELISA. RESULTS: Children with acute bronchiolitis (AB; n = 36), recurrent wheeze (RW; n = 17) and upper respiratory infection (URI; n = 18) were enrolled. Respitory syncytial virus was the most commonly detected virus in all groups. IL-10 concentrations were significantly increased in AB (median, 0.019 ng/mL) when compared to URI (median, 0.006 ng/mL) or to RW (median, 0.007 ng/mL; P < 0.05). Neutrophils were the predominant cells in the cytological analysis in all subjects. CONCLUSION: These data argue that host-response factors are important in determining the clinical phenotype, independent of the causative virus.     

Effects of ambient particulate matter on peak expiratory flow rates and respiratory symptoms of asthmatics during Asian dust periods in Korea

OBJECTIVE: Dust generating events frequently produce ambient dust particles that are less than 10 microm in diameter, and these have been linked to adverse effects in the general population. However, the evidence linking these particles to adverse effects on the airways of asthmatic individuals is limited. The objective of this study was to investigate the possible adverse effects of Asian dust events on the respiratory functions and symptoms of subjects with bronchial asthma. METHODOLOGY: From March to June 2002, individuals were enrolled who had been diagnosed as having asthma by bronchial challenge or by their bronchodilator response. The patients were divided into three groups according to asthma severity: mild, moderate and severe. Patients with other major disease states were excluded. Patients completed twice-daily diaries monitoring PEF, respiratory symptoms, and daily activities. The daily and hourly mean levels of particulate matter <10 microm in diameter (PM(10)), as well as nitrogen dioxide (NO(2)), sulphur dioxide (SO(2)), ozone (O(3)) and carbon monoxide (CO) were measured at 10 monitoring sites in Incheon, Korea. RESULTS: Dust events occurred 14 times during the study period. On dusty days there were increased levels of PM(10), decreased levels of NO(2) and SO(2), and no change in the CO levels, compared to the levels on control days. An increase in PM(10) concentration was associated with increases in PEF variability of >20% (P<0.05), more night-time symptoms (P<0.05), and a decrease in the mean PEF (P<0.05), calculated by longitudinal data analysis. In contrast, there was no association between the PM(10) levels and bronchodilator inhaler use or daytime respiratory symptoms. Using a general additive Poisson regression model, a borderline association was noted between PM(10) and respiratory symptoms, with a relative risk of 1.05 (95% confidence interval (CI), 0.99--1.17). There was no association between the PM(10) concentrations and PEF measurements, with PEF variability of >20% between the morning and evening values and a relative risk of 1.05 (95% CI, 0.89--1.24) in all subjects. CONCLUSIONS: This study provides evidence that Asian dust events are impacting on the respiratory symptoms of subjects with bronchial asthma, and ambient air pollution, particularly elevated PM(10), might be one of the aggravating factors.     

Diabetes per se and metabolic state influence gene expression in tissue-dependent manner of BB/OK rats

BACKGROUND: Several epidemiologic studies have clearly established that long-term near normoglycaemia strongly protects against onset and progression of late complication of diabetes. Therefore, insulin treatment plays a crucial role in determining the quality of life of affected individuals. Here we studied the effects of exogenous insulin on gene expression levels in well- and poorly compensated diabetic subjects in comparison to non-diabetic BB/OK rats to find out whether diabetes per se and the quality of insulin treatment have an effect on gene expression and whether it is tissue specific. METHODS: Six non-diabetic and 12 diabetic BB/OK rats were studied. Diabetic subjects were either treated with insulin implants (well compensated) or treated with 1U insulin daily (poorly compensated) to guarantee survival. Four weeks after onset of diabetes, the animals were killed and expression of Yy1, Ppargamma, Nfkappab, Pref-1, Tgfb1, Il-10, and Lepr was measured in thymus, spleen, liver, heart, and bone. RESULTS: In general, between diabetic and non-diabetic subjects, significant expression changes were detected in spleen for Il-10, in heart for Il-10 and Ppargamma, in liver for Yy1, Nfkappab, and Lepr, as well as in bone for all genes studied except Tgfb1. Except Lepr, no expression changes were observed in thymus. Between well- and poorly compensated rats, significant differences on expression level were found for Yy1 (liver), Ppargamma (heart), Nfkappab (bone), Pref-1 (spleen), and Lepr (thymus, liver, heart). CONCLUSION: The insulin treatment compensates not only metabolic disturbances but also changes gene expression profile in BB/OK rats in a tissue-dependent manner.     

Growth hormone and body composition in children younger than 2 years with Prader-Willi syndrome

OBJECTIVES: To assess body composition of infants with Prader-Willi syndrome (PWS) by using deuterium dilution and investigating the efficacy of early institution of growth hormone (GH) therapy in increasing lean mass (LM) and preventing massive obesity. STUDY DESIGN: One group of 11 children with PWS <2 years before and during 30-month GH therapy (GH group) was compared with 6 infants administered only coenzyme Q(10) for 1 year (Q10 group). LM adjusted for height (LM(Ht)) and relative fat mass (%FM(Age)) standard deviation scores (SDS) were calculated from data of 95 healthy children. RESULTS: Initially, LM(Ht) of all patients was below the normal average. LM(Ht) decreased by -0.46 +/- 0.3 SD (P=.03) per year in the Q10 group but rose by 0.25 +/- 0.3 SD (P=.02) per year during GH therapy, normalizing after 30 months (-0.70 +/- 1.0 SD). Despite low to normal weight for height (WfH), %FM(Age) was above the normal average (GH group, 31.0% +/- 4.5%, Q10 group, 32.4% +/- 9.5%). In the Q10 infants, %FM(Age) increased by 0.71 +/- 0.7 SD per year, whereas in the GH group, %FM(Age) remained more stable up to 30 months. CONCLUSIONS: Diminished LM(Ht) found in infants with PWS further declines during the early years. Early institution of GH therapy lifts LM(Ht) into the normal range and delays fat tissue accumulation.     

树突状细胞在小儿哮喘发病机制中的作用

目的　探讨树突状细胞 (DC)在小儿哮喘发病中的可能作用及机制。方法　以Thomas法 ,采用粒 巨噬细胞集落刺激因子 ,白细胞介素 4 (IL 4 )和肿瘤坏死因子α(TNF α)联合培养诱导哮喘患儿外周血DC细胞 ,进而检测DC协同刺激分子B7 1(CD80 )、B7 2 (CD86)的表达 ,DC诱导自体T淋巴细胞的增殖反应 ,以及其分泌的IL 10、IL 12等水平的变化。结果　哮喘患儿外周血DC诱导自体T淋巴细胞增殖反应明显高于对照组 (cpm值分别为 115 6 0± 12 6和 6 5 39± 12 6 ,t =12 1 6 96 ) ,差异有非常显著意义 (P <0 0 1) ;其分泌IL 10水平 [( 3 6± 0 3) μg/L]明显低于对照组 [( 6 9± 0 8) μg/L],差异有非常显著意义 (t=2 0 6 0 8,P <0 0 1) ;分泌IL 12水平 [( 2 9 7± 8 4 )ng/L]也明显低于对照组 [( 4 5 2± 9 8)ng/L],差异有非常显著意义 (t=5 979,P <0 0 1) ;同时 ,哮喘患儿外周血人类白细胞抗原DR( 19 9± 1 3)和协同刺激分子B7 2 (CD86)的表达水平 ( 36 3± 14 0 )明显高于对照组( 10 6± 1 5和 2 4 7± 8 5 ) ,差异有非常显著意义 (t分别 =2 3 30 1和 3 314 ,P均 <0 0 1)。结论　DC可能通过诱导TH1/TH2细胞分化在小儿哮喘发作时起重要作用。其可能的机制系通过DC分泌的细胞因子而起作用。