TARGeted Intraoperative radiotherapy (TARGIT): an innovative approach to partial-breast irradiation

A revolution is challenging the dogma that local treatment for all patients with breast cancer treated with breast conservation therapy must include postoperative radiotherapy delivered to the whole breast. Such prolonged postoperative radiotherapy is a burden to patients and hospitals and forces many women to chose mastectomy instead. Furthermore, for patients receiving chemotherapy, the start of conventional radiotherapy may be delayed so long as to increase the risk of local relapse. These problems might be eliminated if effective radiotherapy could be given as a single treatment intraoperatively, immediately after the surgery. Local recurrence after breast-conserving surgery usually occurs in the portion of the breast in the immediate proximity of the tumor, even when radiotherapy is omitted. Therefore, it should usually be possible to restrict radiotherapy to only the area adjacent to the tumor in selected women. Based on this premise, we have devised a new technique of partial breast irradiation, with the intention of completing all local treatment in a single session. In this article, we elaborate on the rationale and on the different methods of delivering intraoperative radiotherapy. If this approach is validated in ongoing randomized trials, it could save time, money, and breasts.     

The concomitant presence of polymorphic alleles of interleukin-1beta, interleukin-6 and apolipoprotein E is associated with an increased risk of myocardial infarction in elderly men. Results from a pilot study

Genetic background of inflammatory or anti-inflammatory molecules may be helpful in identifying subjects with increased or decrease risk of developing cardiovascular disease. Bi-allele polymorphism (C > T) in the promoter region (-511) of the interleukin-1beta (IL-1beta) gene and the bi-allele polymorphism (G > C) in the promoter region (-174) of interleukin-6 (IL-6) gene were determined in elderly men patients with myocardial infarction (MI) and healthy controls. Each subject was also genotyped for the triallelic polymorphism of the apolipoprotein E epsilon gene. The IL-6C and APOE epsilon4 alleles were independently associated with a mild or moderate increased risk of MI, whilst the allele C of the IL-1beta was not independently linked to MI risk. However, the simultaneous presence of the allele C of IL-1beta, the allele C of IL-6 and epsilon4 allele of APOE was strongly associated with the disease. Data from this cross-sectional study suggest that the functional interaction of these three genes affects pathogenetic mechanisms of MI and an impaired regulation of immune responses plays a pivotal role in the disease. Furthermore, genetic background of inflammatory genes may influence longevity of human species by affecting inflammatory responses associated to cardiovascular diseases. The administration of anti-inflammatory compounds to middle age healthy subjects with increased genetic susceptibility of developing MI might decrease the incidence and prevalence of cardiovascular events in aging.     

ErbB-4 and neuregulin expression in the adult mouse olfactory bulb after peripheral denervation

ErbB-4 is expressed by the periglomerular and the mitral/tufted cells of the adult mouse olfactory bulb (OB) and in the present work we tested whether this expression is regulated by the olfactory nerve input to the OB. Reversible zinc sulphate lesions of the olfactory mucosa were made in adult mice and the deafferented OB analysed by immunohistochemistry, Western blotting and semiquantitative RT-PCR. Following deafferentation, the expression of erbB-4, erbB-2 and neuregulin-1 (NRG-1) mRNAs in the OB was altered. At early stages (7-14 days) after lesion the levels of expression of olfactory marker protein (OMP), tyrosine hydroxylase (TH), erbB-4 and NRG-1 mRNAs were decreased, whilst expression of erbB-2 increased and that of NRG-2 was not significantly altered. We observed at least two distinct time courses for these expression changes. The lowest amounts of mRNA for erbB-4 and NRG-1 were observed at day 7 after lesion, whilst mRNAs for TH and OMP were lowest at day 14. At day 28 after the lesion, when olfactory receptor neuron axons had reinnervated the olfactory bulb, the expression levels of OMP, TH, erbB-2, erbB-4 and NRG-1 were identical to control values. These results indicate that the expression of erbB-4 mRNA and protein in periglomerular and mitral cells is controlled by peripheral olfactory innervation. The tight correlation in NRG-1 and erbB-4 expression levels also suggests a possible functional link that deserves further exploration.     

A nuclear magnetic resonance approach to the comparison of mucoadhesive properties of polysaccharides for ophthalmic uses

Mucoadhesive properties of tamarind seed polysaccharide (TSP) and larch arabinogalactan (AG), which are developed for ophthalmic applications, were investigated by NMR spectroscopy. Polysaccharide to mucin affinities were compared by using ketotifen fumarate as low molecular weight interaction probe. Proton selective relaxation rate measurements revealed enhanced affinity of TSP to mucin with respect to AG.     

Impact of restless legs syndrome and iron deficiency on attention-deficit/hyperactivity disorder in children

OBJECTIVE: Increasing evidence suggests a significant comorbidity between attention-deficit/hyperactivity disorder (ADHD) and restless legs syndrome (RLS). Iron deficiency may underlie common pathophysiological mechanisms in subjects with ADHD plus RLS (ADHD+RLS). To date, the impact of iron deficiency, RLS and familial history of RLS on ADHD severity has been scarcely examined in children. These issues are addressed in the present study. METHODS: Serum ferritin levels, familial history of RLS (diagnosed using National Institutes of Health (NIH) criteria) and previous iron supplementation in infancy were assessed in 12 ADHD+RLS children, 10 ADHD children and 10 controls. RLS was diagnosed using NIH-specific pediatric criteria, and ADHD severity was assessed using the Conners' Parent Rating scale. RESULTS: ADHD symptom severity was higher, although not significantly, in children with ADHD+RLS compared to ADHD. The mean serum ferritin levels were significantly lower in children with ADHD than in the control group (p<0.0005). There was a trend for lower ferritin levels in ADHD+RLS subjects versus ADHD. Both a positive family history of RLS and previous iron supplementation in infancy were associated with more severe ADHD scores. CONCLUSIONS: Children with ADHD and a positive family history of RLS appear to represent a subgroup particularly at risk for severe ADHD symptoms. Iron deficiency may contribute to the severity of symptoms. We suggest that clinicians consider assessing children with ADHD for RLS, a family history of RLS, and iron deficiency.