Effect of flosequinan on exercise capacity and symptoms in severe heart failure.

Twenty patients with severe chronic cardiac failure caused by ischaemic heart disease were treated with flosequinan 100 mg daily or placebo in addition to their existing treatment with diuretics and, in some, digoxin in a randomised double blind trial. After eight weeks of treatment, flosequinan significantly improved treadmill exercise time, increased peak achieved oxygen consumption, and improved the New York Heart Association symptom grade when compared with placebo. One patient in the placebo group died and another was withdrawn because heart failure worsened. One patient in the flosequinan group was lost to follow up but there were no other withdrawals. Flosequinan was well tolerated with few adverse effects, and it may prove to be a useful addition to diuretics and digoxin in the treatment of chronic cardiac failure.     

国产沉香化学成分的研究——Ⅲ.异白木香醇的结构测定和低沸点成分的分离与鉴定

自国产沉香(Aquilaria sinensis)[瑞香科(Thymeleaceae)植物]的挥发油中,经硅胶柱层析和离心薄层层析分离得到一新的倍半萜,命名为异白木香醇(isobaimuxinol),根据光谱(IR,¹HNMR,¹³CNMR,2 D-NMR和MS)分析确定其结构式为(Ⅰ)所示,并用X-光衍射晶体解析进一步确定了其立体化学。同时,也从该植物挥发油的低沸点部分分离得到四个已知化合物:苄基丙酮,对甲氧基苄基丙酮,茴香酸和β-沉香呋喃。这些化合物均为首次从该植物中得到。     

Predictors of growth and body composition in HIV‐infected children beginning or changing antiretroviral therapy

Objectives

The aim of the study was to describe growth and body composition changes in HIV‐positive children after they had initiated or changed antiretroviral therapy (ART) and to correlate these with viral, immune and treatment parameters.

Methods

Ninety‐seven prepubertal HIV‐positive children were observed over 48 weeks upon beginning or changing ART. Anthropometry and bioelectrical impedance analysis results were compared with results from the National Health and Nutrition Examination Survey 1999–2002 (NHANES) to generate z‐scores and with results for HIV‐exposed, uninfected children from the Women and Infants Transmission Study (WITS). Multivariate analysis was used to evaluate associations between growth and body composition and disease parameters.

Results

All baseline lean and fat mass measures were below those of controls from NHANES. Weight, height and fat free mass (FFM) index (FFM/height²) z‐scores increased over time (P=0.004, 0.037 and 0.027, respectively) and the waist:height ratio z‐score decreased (P=0.045), but body mass index and per cent body fat z‐scores did not change. Measures did not increase more than in uninfected WITS controls. In multivariate analysis, baseline height, mid‐thigh circumference and FFM z‐scores related to CD4 percentage (P=0.029, P=0.008 and 0.020, respectively) and change in FFM and FFM index z‐scores to CD4 percentage increase (P=0.010 and 0.011, respectively). Compared with WITS controls, baseline differences in height and mid‐thigh muscle circumference were also associated with CD4 percentage. Case–control differences in change in both subscapular skinfold (SSF) thickness and the SSF:triceps skinfold ratio were inversely associated with viral suppression. No measures related to ART class(es) at baseline or over time.

Conclusions

In these HIV‐positive children, beginning or changing ART was associated with improved growth and lean body mass (LBM), as indicated by FFM index. Height and LBM related to CD4 percentage at baseline and over time. Altered fat distribution and greater central adiposity were associated with detectable virus but not ART class(es) received.     

Analysis of serious non‐AIDS events among HIV‐infected adults at Latin American sites

Objective

Acquired immune deficiency appears to be associated with serious non‐AIDS (SNA)‐defining conditions such as cardiovascular disease, liver and renal insufficiency and non‐AIDS‐related malignancies. We analysed the incidence of, and factors associated with, several SNA events in the LATINA retrospective cohort.

Materials and methods

Cases of SNA events were recorded among cohort patients. Three controls were selected for each case from cohort members at risk. Conditional logistic models were fitted to estimate the effect of traditional risk factors as well as HIV‐associated factors on non‐AIDS‐defining conditions.

Results

Among 6007 patients in follow‐up, 130 had an SNA event (0.86 events/100 person‐years of follow‐up) and were defined as cases (40 with cardiovascular events, 54 with serious liver failure, 35 with non‐AIDS‐defining malignancies and two with renal insufficiency). Risk factors such as diabetes, hepatitis B and C virus coinfections and alcohol abuse showed an association with events, as expected. The last recorded CD4 T‐cell count prior to index date (P=0.0056, with an average difference of more than 100 cells/μL) and area under the CD4 cell curve in the year previous to index date (P=0.0081) were significantly lower in cases than in controls. CD4 cell count at index date was significantly associated with the outcome after adjusting for risk factors.

Conclusions

The incidence and type of SNA events found in this Latin American cohort are similar to those reported in other regions. We found a significant association between immune deficiency and the risk of SNA events, even in patients under antiretroviral treatment.     

Lionfish on the Loose in the Waters off St Vincent

Objective

The purpose of this study was to determine if the exotic venomous species, Pterois volitans (lionfish) had reached as far south as St Vincent in the Caribbean. This predatory marine fish has successfully invaded the waters of the Western Atlantic and the Caribbean. Such success as an exotic invasive species is rare for a predatory marine fish. It is possible that the fish are growing larger and spreading faster than anticipated, thanks to a lower burden of parasites and a paucity of natural predators in their new environment. But prior to this report, no sightings of this species this far south had been reported.

Methods

The authors conducted a search along with the help of local divers and fishermen in the waters of St Vincent.

Results

Approximately one year after the initiation of the search, a juvenile specimen was positively confirmed and captured off the southern coast of St Vincent.

Conclusions

The exotic predatory and venomous red lionfish, Pterois volitans, has successfully invaded marine waters as far south as the Windward Islands. Fishermen in these regions should be aware of this venomous species in the region and physicians must be aware of how to manage stings from such animals.     

Exploiting PI3K/mTOR signaling to accelerate epithelial wound healing

The molecular circuitries controlling the process of skin wound healing have gained new significant insights in recent years. This knowledge is built on landmark studies on skin embryogenesis, maturation, and differentiation. Furthermore, the identification, characterization, and elucidation of the biological roles of adult skin epithelial stem cells and their influence in tissue homeostasis have provided the foundation for the overall understanding of the process of skin wound healing and tissue repair. Among numerous signaling pathways associated with epithelial functions, the PI3K/Akt/mTOR signaling route has gained substantial attention with the generation of animal models capable of dissecting individual components of the pathway, thereby providing a novel insight into the molecular framework underlying skin homeostasis and tissue regeneration. In this review, we focus on recent findings regarding the mechanisms involved in wound healing associated with the upregulation of the activity of the PI3K/Akt/mTOR circuitry. This review highlights critical findings on the molecular mechanisms controlling the activation of mTOR, a downstream component of the PI3K–PTEN pathway, which is directly involved in epithelial migration and proliferation. We discuss how this emerging information can be exploited for the development of novel pharmacological intervention strategies to accelerate the healing of critical size wounds.