Cardiovascular risk profile and frailty in a population-based study of older British men.

BACKGROUND: Frailty in older age is known to be associated with cardiovascular disease (CVD) risk. However, the extent to which frailty is associated with the CVD risk profile has been little studied. Our aim was to examine the associations of a range of cardiovascular risk factors with frailty and to assess whether these are independent of established CVD. METHODS: Cross-sectional study of a socially representative sample of 1622 surviving men aged 71-92 examined in 2010-2012 across 24 British towns, from a prospective study initiated in 1978-1980. Frailty was defined using the Fried phenotype, including weight loss, grip strength, exhaustion, slowness and low physical activity. RESULTS: Among 1622 men, 303 (19%) were frail and 876 (54%) were pre-frail. Compared with non-frail, those with frailty had a higher odds of obesity (OR 2.03, 95% CI 1.38 to 2.99), high waist circumference (OR 2.30, 95% CI 1.67 to 3.17), low high-density lipoprotein-cholesterol (HDL-C) (OR 2.28, 95% CI 1.47 to 3.54) and hypertension (OR 1.79, 95% CI 1.27 to 2.54). Prevalence of these factors was also higher in those with frailty (prevalence in frail vs non-frail groups was 46% vs 31% for high waist circumference, 20% vs 11% for low HDL and 78% vs 65% for hypertension). Frail individuals had a worse cardiovascular risk profile with an increased risk of high heart rate, poor lung function (forced expiratory volume in 1 s (FEV1)), raised white cell count (WCC), poor renal function (low estimated glomerular filtration rate), low alanine transaminase and low serum sodium. Some risk factors (HDL-C, hypertension, WCC, FEV1, renal function and albumin) were also associated with being pre-frail. These associations remained when men with prevalent CVD were excluded. CONCLUSIONS: Frailty was associated with increased risk of a range of cardiovascular factors (including obesity, HDL-C, hypertension, heart rate, lung function, renal function) in older people; these associations were independent of established CVD.

An amelanotic malignant melanoma masquerading as hypergranulation tissue.

We report a case of amelanotic malignant melanoma occurring in the nail sulcus of the hallux, which on initial presentation was mistaken for hypergranulation tissue due to an in-growing toenail. We highlight the importance of this differential diagnosis as such lesions can have serious sequelae.

Biologic agents used to treat rheumatoid arthritis and their relevance to podiatrists: a practice update.

This review considers the pharmacological management of rheumatoid arthritis including the role of anti-tumour necrosis factor alpha (TNFalpha) agents, as a precursor to highlighting some of the issues for podiatrists involved in the care of patients on this particular medication.

Analysis of HMG protein binding to DNA modified with the anticancer drug cisplatin.

Cisplatin (CDDP) is an effective and widely used cancer chemotherapy drug. High mobility group (HMG) proteins 1 and 2 have been shown to bind with high affinity to CDDP-DNA. In this study we analyzed the interaction of HMG proteins with CDDP-DNA. We demonstrate that after binding, HMG proteins can be removed from CDDP-DNA leaving the Pt adducts intact and capable of rebinding HMG proteins. Furthermore, the very HMG proteins that have been removed remain functionally viable and capable of rebinding CDDP-DNA. We also investigated the role that Cys residues play in protein binding. Replacement of Cys 45 or Cys 106 with a Ser residue reduced HMG2 protein binding to CDDP-DNA. These results indicate that Cys residues play a critical role in the high affinity binding of this protein to CDDP-DNA. From these findings, we speculate that the intracellular oxidative environment could affect the redox state of protein thiols in HMG1 and HMG2 and in addition, regulate the ability of these proteins to recognize cis-Pt-DNA adduct formation in tumor cells.

A post-labeling technique for the iodination of DNA damage recognition proteins.

Major advances have recently been made in understanding the nucleotide excision repair pathway in mammalian cells. Although the signaling events responsible for initiating this process are not known, they probably involve proteins, i.e., damage recognition proteins (DRPs), which detect specific types of DNA damage. In this report, we describe a technique for labeling DNA damage recognition proteins. The procedure utilizes iodogen to radio-iodinate proteins bound to DNA modified with the cancer chemotherapy drug, cisplatin. Following iodination, bound proteins are eluted and analyzed on SDS-polyacrylamide gels. We have optimized this procedure such that the labeling reactions are rapid and employ small amounts of 125I. Using this procedure, we demonstrate that proteins of 28 and 40 kDa in MCF7 human breast epithelial cells bind to CDDP-DNA. This technique is sensitive and potentially will facilitate the identification of DRPs in samples containing limited amounts of protein, such as small tissue biopsy specimens obtained from patients undergoing diagnostic and/or therapeutic treatment.

The isolation and characterisation of a putative adipocyte precursor cell type from the white adipose tissue of the chicken (Gallus domesticus).

The conditions of isolation and culture of a chicken adipose stromal-derived cell strain are described and compared with chicken lung fibroblasts in vitro. The stromal cells accumulated intracellular lipid during the post-confluency culture period, this being by contrast with lung fibroblasts. Much higher levels of intracellular lipid were accumulated by the stromal cells when whole chicken serum or chicken plasma lipoproteins were added to the culture medium. Lipoprotein lipase activity emerged in stromal cells maintained post confluency. This activity was absent from pre-confluent stromal cells and pre- and post-confluent fibroblasts. The incorporation of 14C-acetate, 3H-oleic acid and 14C-glucose into lipids by the stromal cells exhibited a pattern compatible with a concerted shift in the metabolism of the cells towards lipid storage, particularly in the form of triacylglycerols derived from exogenous fatty acids. It is proposed that, in common with the mammalian species previously studied, the white adipose tissue of the chicken (Gallus domesticus) contains a cell type with properties which allow its preliminary identification as an adipocyte precursor cell capable of adipose conversion in vitro. The confirmation of this proposition is amenable to further investigation.

Studies on the expression of adipocyte-specific cell surface antigens during the differentiation of adipocyte precursor cells in vitro.

Using species and cell specific antiadipocyte sera an immunoprecipitation procedure was developed which allowed the nature of adipocyte cell surface antigens to be investigated. Analysis of immunoprecipitates from mature adipocyte plasma membranes of rat, ox and chicken and similar 125I-labelled membranes revealed the presence of specific externally disposed adipocyte specific antigens which were also species specific. For mature cells the specific antigens had molecular weights of 124,000, 92,000 and 59,000 in the case of the rat, 87,000 in the case of the ox and 56,000, 47,000 and 37,000 in the case of the chicken. None of these antigens were cross immunoprecipated by antisera to non-homologous adipocytes. The presence of the antigens at the surface of differentiating rat while adipocyte precursor cells was demonstrated using a labelled-second antibody cellular immunoassay and the expression of this reactivity revealed to be an early event in the differentiation programme of the cells. The increase in cell surface immunoreactivity during the differentiation of the cells was shown to be dependent upon the expression of two of the antigens previously shown to be markers of the mature adipocyte phenotype. The functional identity and possible role of these antigens in the control of adipocyte differentiation in vitro and in vivo now becomes accessible to investigation experimentally.