The effects of enfuvirtide therapy on body composition and metabolic parameters over 48 weeks in the TORO body imaging substudy*

Objective

The aim of the study was to compare the metabolic and morphological effects of enfuvirtide plus an optimized background (OB) regimen vs. OB alone (control group) in treatment‐experienced patients in the T‐20 vs. Optimized Regimen Only (TORO) studies.

Methods

Body composition and metabolic changes were investigated in patients over 48 weeks, based on fasting chemistries, body weight, and other anthropometric measurements. Dual‐energy X‐ray absorptiometry (DEXA) and computed tomography (CT) scans were performed in a patient subgroup (n=155) at baseline and at weeks 24 and 48.

Results

At week 48, mean changes from baseline were similar between treatment groups for glucose, insulin, C‐peptide, total cholesterol, low‐density lipoprotein (LDL) cholesterol, very low density lipoprotein (VLDL) cholesterol, high‐density lipoprotein (HDL) cholesterol and triglyceride levels. The enfuvirtide group experienced a significant increase in body weight [mean change from baseline +0.99 kg; 95% confidence interval (CI) +0.54, +1.44] and, in those who had body scans, there was a significant increase in truncal fat (by DEXA: median change +419.4 g; 95% CI+71.3, +767.5) and total fat [visceral adipose tissue (VAT)+subcutaneous adipose tissue (SAT) by single‐slice abdominal CT scan: median change +25.5 cm²; 95% CI+8.9, +42.0] over 48 weeks; significant increases in these parameters were not seen in the control group. There was no significant change in truncal:peripheral fat ratio in either the enfuvirtide or the control group.

Conclusion

The addition of enfuvirtide to an OB regimen does not appear to have unfavourable effects on fat distribution or metabolic parameters.     

Chronic mercury exposure at different concentrations produces opposed vascular responses in rat aorta

Mercury chloride exposure for 30 days decreases NO bioavailability and increases oxidative stress. However, the mechanisms underlying the effects of mercury on the cardiovascular system are not completely understood, and it is not known if they are dose‐dependent or if some concentrations have no harmful effects. Thus, we investigated the effects of chronic exposure to doses low (half) and high (2.5‐fold higher) than that needed to obtain 29 nmol/L of HgCl₂ on the vascular function. Three‐month‐old male Wistar rats received intramuscular (i.m.) HgCl₂ for 30 days and were divided in three groups: lower (Low Hg); higher (High Hg); and saline was used as the control. High Hg exposure increased the contractile response to phenylephrine (PHE) in aortic rings, but Low Hg reduced it. The hyporesponsiveness in the Low Hg rats was blunted by endothelial denudation and NOS inhibition with l ‐NAME (100 μmol/L). The phosphorylated‐eNOS/eNOS protein ratio increased in the aortas of Low Hg rats. In the High Hg group, endothelial denudation increased the PHE‐induced contractions, while l ‐NAME had no effects and indomethacin (10 μmol/L), losartan (10 μmol/L) and apocynin (30 μmol/L) reduced this response. In the High Hg group, protein levels of the NADPH oxidase subunit gp91phox and cyclooxygenase‐2 increased. Our results support previous suggestions that High Hg increases oxidative stress that might activate an inflammatory cascade and the renin‐angiotensin system. However, very low Hg concentrations below the level considered safe still reduced vascular reactivity, suggesting the need for special attention to continuous exposure as a putative cause of increased cardiovascular risk.     

Sensitivity and specificity of first screen mammography in the Canadian National Breast Screening Study: a preliminary report from five centers

Sensitivity and specificity of first screen mammography in a randomized screening trial at five centers are reported. A total of 23,101 women underwent mammography; in 139, breast cancer was detected at first screening; in 20, less than 12 months after first screening; and in 47, at second screening. All 206 cancer cases were histologically confirmed, and 174 were defined as being detectable at first screening. Average length of follow-up for all women was 3.2 years. Interpretations of first screen mammograms by the center radiologists were matched to known outcomes. Simultaneous blind review was performed by a single reference radiologist with mammograms from all 206 cancer cases and those of a random sample of 739 women not known to have breast cancer at 15 months or more after initial screening. Overall, the five screening centers achieved a sensitivity of 69% (range, 60%-78%), a specificity of 94% (range, 93%-96%), a positive predictive value of 8.6% (range, 3%-16%), and a negative predictive value of 99.7% (range, 99.6%-99.9%).     

Antiproliferative effects of natural interferon beta alone and in combination with natural interferon gamma on human breast carcinomas in nude mice

Summary Nude mice bearing bilateral xenografts of human breast carcinoma cells (MCF-7 and BT20) were treated with 2 or 4 5-day cycles of intralesional (i.l.) injections of human natural interferon beta (nIFN-) alone or in combination with human natural interferon gamma (nIFN-). The injections were administered to only 1 of the 2 tumors in each animal, thus making it possible to assess at the same time local therapeutic effects in the injected tumors and systemic effects in the contralateral ones. When n-IFN- was used as a single agent only mild local antitumor effects and virtually no systemic effects were observed. In contrast, the combined administration of nIFN-/nIFN- produced marked antiproliferative effects, presumably as a result of the synergistic action of type I and type II IFNs. These effects ranged from complete regression documented histologically in 2 MCF-7 tumors to varying degrees of growth inhibition with persistence of residual microscopic or grossly detectable tumor. Local effects were more pronounced than systemic effects. The therapeutic efficacy of nIFN- proved to be greater than that of recombinant interferon beta (rIFN-). In MCF-7 tumors nIFN- appeared to be less effective than nIFN-, whereas the opposite was true for BT 20 tumors.     

Contraception within six-month postpartum in rural Vietnam: Implications on family planning and maternity services

Objectives?This longitudinal study documents contraception practice and factors influencing contraception decision within the first six months postpartum, amongst women residing in the rural Northern Central region of Vietnam.

Methods?A sample of 463 rural women who gave birth during August-October 2002 were recruited and interviewed at one, 16 and 24 weeks postpartum.

Results?The proportion of contraceptive users at weeks 16 and 24 were 17% and 43% respectively. At week 24, of contraceptive users, 57% used IUD, 25% used condom, and 14% used traditional methods. Logistic regression analysis found age, sufficient knowledge on contraceptives and husband/partner opinion can significantly affect the contraception decision.

Conclusions?In order to improve the situation, health authorities should be encouraged to provide counselling on postpartum contraceptive methods during ante- and postnatal care visits. Health education on family planning and breastfeeding should also involve the husband/partner group taking into account local socio-cultural features.     

Clinical involvement in daughters of men with fragile X‐associated tremor ataxia syndrome

Chonchaiya W, Nguyen DV, Au J, Campos L, Berry‐Kravis EM, Lohse K, Mu Y, Utari A, Hervey C, Wang L, Sorensen P, Cook K, Gane L, Tassone F, Hagerman RJ. Clinical involvement in daughters of men with fragile X‐associated tremor ataxia syndrome. Women with the fragile X mental retardation 1 (FMR1) premutation often have concerns about neurological and medical problems, as they become older and if their fathers experience fragile X‐associated tremor/ataxia syndrome (FXTAS). We therefore determined the prevalence of these problems in 110 daughters of men with FXTAS [mean age of 44.8 years (SD 8.2)]. We compared them with 43 female controls with normal FMR1 alleles [mean age of 43.8 years (SD 8.1)] and 36 premutation carrier daughters of parents with the premutation, but without FXTAS [mean age of 43.5 years (SD 7.7)]. Overall, daughters of men with FXTAS have a higher prevalence of neurological symptoms including tremor, balance problems, memory problems, and dizziness, menopausal symptoms, and psychiatric involvement including sleep problems and anxiety when compared with non‐carrier female controls. Reported balance problems and menopausal symptoms were significantly higher in daughters of men with FXTAS than in carrier daughters of parents without FXTAS, suggesting the potential influence of background gene effects. Therefore, neurological, psychological and gynecological surveillance should be warranted to better provide appropriate counseling, management and care for daughters of men with FXTAS. Biological markers of additional gene effects that predispose individuals with the premutation to FXTAS need to be developed.