Body weight, diabetes incidence vascular events and survival 15 years after very low calorie diet in community medical clinics in the UK.

Objective: To assess weight loss maintenance, diabetes status, mortality and morbidity 15 years after a very low calorie diet programme (VLCD) in patients with obesity. Design: General practice data bases were interrogated for subjects coded for group therapy with VLCD in the 1990s. Causes of death, occurrence of vascular disease and remission or development of diabetes were ascertained from patient records and national stroke and cardiovascular disease data bases. Results: 325 subjects engaged in the programme and had sufficient data for analysis. Baseline characteristics were: age 47.8±12. 8 years; body mass index (BMI) 36.1±6.8 kg/m2; 79.1% female/20.9% male; 13.5% had type 2 diabetes. After 15±4 years weight had changed from 97.9±19 kg at baseline to 100±20.8 kg. 10 with diabetes at baseline were in remission at 3 months, but only two remained in remission at 5 years. 50 new cases of type 2 diabetes and 11 of impaired fasting glucose developed during follow-up. Only 5.9% who remained healthy at follow-up had maintained >10% body weight reduction. Neither diabetes incidence nor diabetes free survival were related to percentage body weight lost during VLCD. Only baseline BMI was related to development of new impaired fasting glucose or diabetes by 15 years (p=0.007). 37 subjects had a cardiovascular event. Age (p=0.000002) and degree of weight loss after VLCD (p=0.03) were significantly associated with subsequent vascular events. Conclusion: Long-term maintenance of weight loss after VLCD was rare in this single centre retrospective study 15 years later. Glucose intolerance developed in 21.4%. Lasting remission of type 2 diabetes or prevention of later glucose intolerance were not achieved. Vascular events were more frequent in those who lost most weight. Risk management during weight regain should be studied in future to assess potential for reduction in adverse cardiovascular outcomes.

A comparison of two FMRI protocols for eliciting hippocampal activation.

PURPOSE: Previous research suggests that the hippocampus is modulated both by stimulus novelty and by the extent to which relational processing (formation of associations) occurs during episodic encoding. The aim of this study was to compare hippocampal activation patterns measured by functional magnetic resonance imaging (fMRI) during encoding protocols emphasizing either novelty or relational processing. METHODS: fMRI was performed on 32 healthy volunteers while they encoded complex visual scenes or unrecognizable scrambled versions of the same scenes. In the Novelty contrast, encoding of novel scenes was compared with encoding of a repeated pair of scenes. In the Relational Processing contrast, semantic encoding of novel scenes was compared with structural encoding of scrambled scenes. RESULTS: Both protocols elicited bilateral hippocampal activation. Overall mean activation values were similar for the two protocols, but the Relational Processing protocol resulted in a larger volume of hippocampal activation. The pattern of activation along the longitudinal hippocampal axis differed for the two protocols. The Novelty contrast produced stronger activation in the posterior hippocampus, whereas the Relational Processing contrast produced stronger activation in the anterior hippocampus. CONCLUSIONS: Hippocampal activation is determined by both stimulus novelty and degree of relational processing during encoding. Given the importance of anterior hippocampal pathology in temporal lobe epilepsy, an approach emphasizing modulation of relational processing may be preferable for clinical fMRI of the medial temporal lobes.

Biologic and genetic characterization of a panel of 60 human immunodeficiency virus type 1 isolates, representing clades A, B, C, D, CRF01_AE, and CRF02_AG, for the development and assessment of candidate vaccines.

A critical priority for human immunodeficiency virus type 1 (HIV-1) vaccine development is standardization of reagents and assays for evaluation of immune responses elicited by candidate vaccines. To provide a panel of viral reagents from multiple vaccine trial sites, 60 international HIV-1 isolates were expanded in peripheral blood mononuclear cells and characterized both genetically and biologically. Ten isolates each from clades A, B, C, and D and 10 isolates each from CRF01_AE and CRF02_AG were prepared from individuals whose HIV-1 infection was evaluated by complete genome sequencing. The main criterion for selection was that the candidate isolate was pure clade or pure circulating recombinant. After expansion in culture, the complete envelope (gp160) of each isolate was verified by sequencing. The 50% tissue culture infectious dose and p24 antigen concentration for each viral stock were determined; no correlation between these two biologic parameters was found. Syncytium formation in MT-2 cells and CCR5 or CXCR4 coreceptor usage were determined for all isolates. Isolates were also screened for neutralization by soluble CD4, a cocktail of monoclonal antibodies, and a pool of HIV-1-positive patient sera. The panel consists of 49 nonsyncytium-inducing isolates that use CCR5 as a major coreceptor and 11 syncytium-inducing isolates that use only CXCR4 or both coreceptors. Neutralization profiles suggest that the panel contains both neutralization-sensitive and -resistant isolates. This collection of HIV-1 isolates represents the six major globally prevalent strains, is exceptionally large and well characterized, and provides an important resource for standardization of immunogenicity assessment in HIV-1 vaccine trials.