Initiatives to reduce postoperative surgical site infections of the head and neck cancer surgery with a special emphasis on developing countries

Introduction: Surgery in patients with head and neck cancers is frequently complicated by multiple stages of procedure that includes significant surgical removal of all or part of an organ with cancer, tissue reconstruction, and extensive neck dissection. Postoperative wound infections, termed ‘surgical site infections’ (SSIs) are a significant impediment to head-and-neck cancer surgery and recovery, and need to be addressed.

Areas covered: Approximately 10–45% of patients undergoing head-and-neck cancers surgery develop SSIs. SSIs can lead to delayed wound healing, increased morbidity and mortality as well as costs. Consequently, SSIs need to be avoided where possible, as even the surgery itself impacts on patients’ subsequent activities and their quality of life, which is exacerbated by SSIs. Several risk factors for SSIs need to be considered to reduce future rates, and care is also needed in the selection and duration of antibiotic prophylaxis.

Expert commentary: Head and neck surgeons should give personalized care especially to patients at high risk of SSIs. Such patients include those who have had chemoradiotherapy and need reconstructive surgery, and patients from lower and middle-income countries and from poorer communities in high income countries, who often have high levels of co-morbidity because of resource constraints.     

Quantification of refractive error: comparison of autorefractor and focometer.

PURPOSE: The advantages of a focometer (FOCOMETER) over other methods of refraction for use in developing countries are that it is lightweight, compact, relatively inexpensive, fairly quick, and easy to use with minimal training. This clinical trial compared the repeatability, validity, and ease of use of the focometer with an autorefractor. METHODS: The refractive status of the right eye of 80 participants was determined with an autorefractor (Canon RK3). Three measurements were also taken with the focometer. RESULTS: The spherical equivalent (M) of the focometer was 0.25 D more positive than the autorefractor (p < 0.001) and 84% of measurements were within 0.75 D of the autorefractor. The autorefractor detected astigmatism in 91% (73) of the eyes, whereas the focometer identified only 32% (26). The design of the clock target restricts cylinder axis accuracy to the nearest 15 degrees . There was evidence of a learning effect for the focometer: the second and third measurements were more repeatable in the untrained group. There were no differences between the mean (1.03 +/- 2.28) and third focometer (-1.05 +/- 2.32) measurements (p = 0.34). However, using the third focometer measurement, 94% of participants had visual acuities of at least 6/12(-2). CONCLUSIONS: This study highlighted the focometer's restricted power range, inaccuracy of astigmatism and axis determination, and dependence on subject understanding and compliance. Therefore, in most clinical settings, the focometer would not be adequate for quantifying refractive error, but the focometer spherical equivalent was within acceptable limits of the autorefractor, and the visual acuity with lenses determined by the focometer indicates its potential usefulness in public health settings, especially where only spherical ready-made spectacles are dispensed. There may be more cost-effective ways to determine refractive error in these circumstances. A potentially important enhancement in focometer methodology that improves its ease of use was identified: use only the third measurement for each eye.     

Thermodynamic stability of wild-type and mutant p53 core domain

Some 50% of human cancers are associated with mutations in the core domain of the tumor suppressor p53. Many mutations are thought just to destabilize the protein. To assess this and the possibility of rescue, we have set up a system to analyze the stability of the core domain and its mutants. The use of differential scanning calorimetry or spectroscopy to measure its melting temperature leads to irreversible denaturation and aggregation and so is useful as only a qualitative guide to stability. There are excellent two-state denaturation curves on the addition of urea that may be analyzed quantitatively. One Zn²⁺ ion remains tightly bound in the holo-form of p53 throughout the denaturation curve. The stability of wild type is 6.0 kcal (1 kcal = 4.18 kJ)/mol at 25°C and 9.8 kcal/mol at 10°C. The oncogenic mutants R175H, C242S, R248Q, R249S, and R273H are destabilized by 3.0, 2.9, 1.9, 1.9, and 0.4 kcal/mol, respectively. Under certain denaturing conditions, the wild-type domain forms an aggregate that is relatively highly fluorescent at 340 nm on excitation at 280 nm. The destabilized mutants give this fluorescence under milder denaturation conditions.     

Postprandial induction of chaperone gene expression is rapid in mice.

Molecular chaperones assist in the biosynthesis and processing of proteins. Most chaperones are induced by physiological stresses. We have shown that dietary energy restriction decreases the mRNA and protein levels of many endoplasmic reticulum chaperones in the livers of mice. Here, we have investigated the response of chaperone mRNA to feeding. Control and 50% energy-restricted C3B10RF1 mice were deprived of food for 24 h, fed, and killed 0, 1.5, 5 or 12 h after feeding. Chaperone mRNAs were strongly induced as early as 1.5 h after feeding in control and energy-restricted mice. The integrated levels of these mRNA over 24 h were significantly lower in energy-restricted mice. The mRNA response to energy intake was mirrored over the course of days in the level of chaperone protein. A similar but smaller response to feeding was found in kidney and muscle. Puromycin and cycloheximide failed to inhibit the feeding response, suggesting that feeding releases chaperone expression from an unstable inhibitor. Studies with dibutyryl-cAMP- and glucagon-supplemented, normal and streptozotocin-diabetic mice suggest that glucagon and insulin may be mediators of the feeding response. Adrenalectomy enhanced the feeding induction, but dexamethasone administration had no effect. Thus, postprandial changes in insulin and glucagon may link chaperone gene expression to feeding, possibly in several tissues including liver.     

Progress toward re‐engineering non‐ribosomal peptide synthetase proteins: a potential new source of pharmacological agents

Many important pharmaceutical agents, including vancomycin, bleomycin, cyclosporin, and several antibiotics, are produced by non‐ribosomal peptide synthetase (NRPS) enzymes in microorganisms. The NRPS pathway produces an extensive library of products using multienzyme complexes acting in an assembly‐line fashion. Engineering an NRPS system to produce an even greater variety of products, some of which may also have beneficial therapeutic value, would be an enormous advantage. Several approaches have been successful in generating novel NRPS products: mutational biosynthesis during which nonnatural substrates are fed to an organism; domain and module swapping between different species to generate hybrid enzymes; and rational site‐directed mutagenesis, based either on phylogeny or computational prediction, intended to switch substrate specificity and produce altered products. This review will highlight the progress in these areas and describe research in the future that will extend the capacity for re‐engineering NRPS systems. Drug Dev. Res. 66:9–18, 2006. © 2006 Wiley‐Liss, Inc.