Doctor–patient concordance during HIV treatment switching decision‐making

Objectives

The aim of the study was to explore levels of doctor–patient concordance during the making of decisions regarding HIV treatment switching and stopping in relation to patient health‐related outcomes.

Methods

Adult patients attending five HIV clinics in the United Kingdom were requested to complete the study questionnaire, which included a Concordance Scale, and measures of symptoms [Memorial Symptom Assessment Short Form (MSAS) index], quality of life (EuroQol), satisfaction, adherence and sexual risk behaviour. Clinical health measures (HIV viral load and CD4 cell count) were also obtained. A total of 779 patients completed the questionnaire, giving a response rate of 86%; of these 779 patients, 430 had switched or stopped their HIV treatment and were thus eligible for inclusion. Of these patients, 217 (50.5%) fully completed the Concordance Scale.

Results

Concordance levels were high (88% scored between 30 and 40 on the scale; score range 10–40). Higher concordance was related to several patient outcomes, including: better quality of life (P=0.003), less severe and burdensome symptom experience (lower MSAS‐physical score, P=0.001; lower MSAS‐psychological score, P=0.008; lower MSAS‐global distress index score, P=0.011; fewer symptoms reported, P=0.007), higher CD4 cell count (at baseline, P=0.019, and 6–12 months later, P=0.043) and greater adherence (P=0.029).

Conclusions

High levels of doctor–patient concordance in HIV treatment decision‐making are associated with greater adherence and better physical and psychological functioning. More research is needed to establish a causal relationship between concordance and these outcomes.     

肠道树突状细胞的特性及功能研究

树突状细胞(DC)是目前所知机体内功能最强的专职性抗原递呈细胞．在肠道内,树突状细胞不但能对致病菌产生免疫应答,而且能对肠腔内共生菌及各类食物蛋白产生免疫耐受．因此,了解DC的功能及相关作用机制对研究肠道免疫屏障具有重要意义．现就肠道树突状细胞在免疫、耐受及疾病发生过程中的作用作一综述,旨在为研究肠道屏障功能提供有益的帮助．     

Activation of human neutrophils by monoclonal antibody PMN7C3: cell movement and adhesion can be triggered independently from the respiratory burst

Anti-neutrophil monoclonal antibody PMN7C3 (IgG3) recognizes glycoproteins bearing the oligosaccharide lacto-N-fucopentaose III, including the C3bi receptor, LFA-1, and p150,95 on the plasma membrane and a group of granule-associated glycoproteins. We have previously shown that binding of this antibody to polymorphonuclear leukocytes (PMNs) stimulates a transient rise in cytosolic free calcium concentration but does not trigger the neutrophil respiratory burst. We now demonstrate that binding of PMN7C3 (and five other monoclonal antibodies recognizing the same antigen) to human neutrophils activates several other cellular responses. Addition of PMN7C3 to monolayers of neutrophils induces a rapid change in cell shape followed by pseudopod formation and increased migration. With incubation at 37 degrees C, the neutrophils aggregate in clusters (leukoagglutination). Quantitation of cell movement in a multiwell chemotaxis assembly or by migration of PMNs under agarose revealed that PMN7C3 is both chemotactic and chemokinetic. Pretreatment with the antibody inhibits subsequent chemotactic response to other stimuli. Monoclonal antibodies binding to other neutrophil antigens do not mimic these effects. These data suggest that cell movement and adhesion can be triggered independently from the respiratory burst. PMN7C3 may be a useful probe with which to study the events that link receptor-ligand binding to cellular response.     

Helicobacter pylori stimulates inducible nitric oxide synthase expression and activity in a murine macrophage cell line

BACKGROUND & AIMS: Helicobacter pylori uniquely colonizes the human stomach and produces gastric mucosal inflammation. High-output nitric oxide production by inducible nitric oxide synthase (iNOS) is associated with immune activation and tissue injury. Because mononuclear cells comprise a major part of the cellular inflammatory response to H. pylori infection, the ability of H. pylori to induce iNOS in macrophages was assessed. METHODS: H. pylori preparations were added to RAW 264.7 murine macrophages, and iNOS expression was assessed by Northern blot analysis, enzyme activity assay, and NO2- release. RESULTS: Both whole H. pylori and French press lysates induced concentration-dependent NO2- production, with peak levels 20-fold above control. These findings were paralleled by marked increases in iNOS messenger RNA and enzyme activity levels. iNOS expression was synergistically increased with interferon gamma, indicating that the H. pylori effect can be amplified by other macrophage-activating factors. Studies of lipopolysaccharide (LPS) content and polymyxin B inhibition of LPS suggested that the H. pylori effect was attributable to both LPS- dependent and -independent mechanisms. CONCLUSIONS: iNOS expression in macrophages is activated by highly stable H. pylori products and may play an important role in the pathogenesis of H. pylori-associated gastric mucosal disease. (Gastroenterology 1996 Dec;111(6):1524-33)     

Developmental programming by high fructose decreases phosphorylation efficiency in aging offspring brain mitochondria,correlating with enhanced UCP5 expression

Fructose has recently been observed to affect brain metabolism and cognitive function in adults. Yet, possible late-onset effects by gestational fructose exposure have not been examined. We evaluated mitochondrial function in the brain of aging (15 months) male offspring of Fischer F344 rat dams fed a high-fructose diet (50% energy from fructose) during gestation and lactation. Maternal fructose exposure caused a significantly lower body weight of the offspring throughout life after weaning, while birth weight, litter size, and body fat percentage were unaffected. Isolated brain mitochondria displayed a significantly increased state 3 respiration of 8%, with the substrate combinations malate/pyruvate, malate/pyruvate/succinate, and malate/pyruvate/succinate/rotenone, as well as a significant decrease in the P/O₂ ratio, compared with the control. Uncoupling protein 5 (UCP5) protein levels increased in the fructose group compared with the control (P=0.03) and both UCP5 mRNA and protein levels were inversely correlated with the P/O₂ ratio (P=0.008 and 0.03, respectively), suggesting that UCP5 may have a role in the observed decreased phosphorylation efficiency. In conclusion, maternal high-fructose diet during gestation and lactation has long-term effects (fetal programming) on brain mitochondrial function in aging rats, which appears to be linked to an increase in UCP5 protein levels.