Cancer and non-cancer brain and eye effects of chronic low-dose ionizing radiation exposure

ABSTRACT: According to a fundamental law of radiobiology ("Law of Bergonie and Tribondeau", 1906), the brain is a paradigm of a highly differentiated organ with low mitotic activity, and is thus radio-resistant to stochastic effects of radiation. This assumption has been challenged by recent evidence discussed in the present review. The brain is among the most critical dose-limiting organs in radio-therapy, mainly due to the development of cognitive dysfunction following white matter disruption, since radio-sensitive oligodendrocyte precursor stem cells have mitotic activity and are responsible for white matter integrity and repair in the adult brain. The neuro-vascular unit is also vulnerable to radiation effects, and cerebro-vascular atherosclerotic damage is now considered proven with epidemiological evidences for doses > 500 mSv. Ionizing radiation is an established environmental cause of brain cancer. Although direct evidence is lacking in contemporary fluoroscopy due to obvious sample size limitation, limited follow-up time and lack of focused research, anecdotal reports of clusters have appeared in the literature, raising the suspicion that brain cancer may be a professional disease of interventional cardiologists. In addition, although terminally differentiated neurons have reduced or mild proliferative capacity, and are therefore not regarded as critical radiation targets, adult neurogenesis occurs in the dentate gyrus of the hippocampus and the olfactory bulb, and is important for mood, learning/memory and normal olfactory function, whose impairment is a recognized early biomarker of neurodegenerative diseases. The head doses involved in radiotherapy are high, usually above 2 Sv, whereas the low-dose range of professional exposure typically involves lifetime cumulative whole-body exposure in the low-dose range of <200 mSv, but with head exposure which may (in absence of protection) arrive at a head dose equivalent of 1 to 3 Sv after a professional lifetime (corresponding to a brain dose around 500 mSv). At this point, a systematic assessment of brain (cancer and non-cancer) effects of chronic low-dose radiation exposure in interventional cardiologists and staff is needed.     

Surgical correction of Tessier number 0 cleft

The no. 0-14 cleft involves the midline of the face and cranium. It may include both a true and a false median cleft lip, with or without associated hypotelorism or hypertelorism. The no. 0 cleft is the most common of the craniofacial clefts. The objective of this study was to review the functional outcome and aesthetic results of the different techniques applied for each case. We have conducted a retrospective analysis of our series consisting of 32 cases of Tessier no. 0 cleft, in the period between 1997 and 2007. The patients were divided into 2 groups: those with the true median cleft and those with the false median cleft. The clinical findings, lip malformation, alveolar cleft, nasal appearance, septal involvement, associated deformities, and surgical procedures, were all reviewed. Holoprosencephaly was present in 9 cases, with a false median cleft upper lip and an absence of the premaxilla, septum, and columella (only 1 patient underwent lip and columella reconstruction at 2 years of age). Nine patients had an incomplete median cleft lip. Seven of these cases had associated median alveolar cleft, and 1 had an intranasal tumor, associated with lipoma of corpus callosum, characteristic of the Pai syndrome. Six cases of a bifid nose were seen, 2 of which were associated with an alveolar median cleft and hypertelorism. An isolated median alveolar cleft was present in 7 cases, 2 of them associated with a no. 30 cleft. This article presents a large series of Tessier no. 0 cleft, describing the differences between the false and the true median cleft. The surgical procedures may vary in relation to the type of involvement.     

The treatment and prognosis of dermatomyositis: an updated review

Dermatomyositis (DM) is an idiopathic inflammatory myopathy. The mainstay of treatment for DM is oral corticosteroids. However, the dose and length of treatment is debated. Adding to the confusion, there have been no randomized controlled studies comparing the use of various corticosteroid doses and taper rates, and no controlled long-term studies assessing the hypothesis that, unlike systemic lupus erythematous, patients with DM can often achieve long-term remission off therapy. This literature review supports an approach that prednisone should be started at about 1 mg/kg/d, which is then tapered slowly based on the response. As patients respond differently to prednisone, additional therapies may be necessary. When to initiate these therapies requires clinical judgment. In addition, as we learn more about the pathophysiology of DM, newer medications that target specific mechanisms in the immune response may help us better treat the disease. Evidence-based data with long-term follow-up will allow for selection of the best treatment to maximize long-term remission, not simply short-term lowering of the systemic corticosteroid dose.     

Prevalence and factors associated with behavioral disorders in adolescents: a population-based study

This study proposed to estimate the prevalence of behavioral disorders and associated factors in adolescents (11-15 years), using a cross-sectional design (n = 1,145). Subjects answered a self-administered questionnaire. Behavioral disorder was assessed with the Mini International Neuropsychiatric Interview (MINI). The study analyzed disorders in relation to gender, age, socioeconomic status, schooling, failure in school, religion, smoking, sedentary lifestyle, alcohol consumption, drug use, depression, and bullying (as victim). Ordinal regression was used for the statistical analysis, with a hierarchical model for the outcome. An estimated 29.2% of the sample presented behavioral disorders. In the multivariate analysis, the odds ratio for a male adolescent to present one additional point on the behavioral disorder scale was 2.04 (95%CI: 1.53-2.71). Alcohol consumption, drug use, and suffering bullying were associated with higher scores on the behavioral disorder scale. The findings also showed that the factors associated with behavioral disorder showed a strong interrelationship between health behaviors in adolescence.     

Biodegradation of microcystins by aquatic Burkholderia sp. from a South Brazilian coastal lagoon

Biological degradation of cyanobacterial hepatotoxin microcystins in estuarine and coastal water samples from the Patos Lagoon estuarine system, a coastal lagoon situated at the southernmost region of Brazil, was observed. Samples of natural surface water were spiked with purified and semi-purified microcystins (MC-LR and [D-Leu(1)]MC-LR) and their concentrations were monitored by HPLC analysis. After 15 days, the toxins were no longer detectable and after 43 days less than 90% of the initial concentration added to the samples was detected by ELISA. The average degradation rates and the exponential decay rate constants from inside and outside of the estuary were similar. A microcystin degradative bacterium was isolated from the estuarine region. Partial sequence of the 16S rDNA showed a 96% homology with the Burkholderia genus. This genus belongs to the beta subdivision on proteobacteria. This is the first report showing the genus Burkholderia as a cyanobacterial toxin degrader.     

Vorinostat synergises with capecitabine through upregulation of thymidine phosphorylase

Background:

Potentiation of anticancer activity of capecitabine is required to improve its therapeutic index. In colorectal cancer (CRC) cells, we evaluated whether the histone deacetylase-inhibitor vorinostat may induce synergistic antitumour effects in combination with capecitabine by modulating the expression of thymidine phosphorylase (TP), a key enzyme in the conversion of capecitabine to 5-florouracil (5-FU), and thymidylate synthase (TS), the target of 5-FU.

Methods:

Expression of TP and TS was measured by real-time PCR, western blotting and immunohistochemistry. Knockdown of TP was performed by specific small interfering RNA. Antitumour activity of vorinostat was assessed in vitro in combination with the capecitabine active metabolite deoxy-5-fluorouridine (5′-DFUR) according to the Chou and Talay method and by evaluating apoptosis as well as in xenografts-bearing nude mice in combination with capecitabine.

Results:

Vorinostat induced both in vitro and in vivo upregulation of TP as well as downregulation of TS in cancer cells, but not in ex vivo treated peripheral blood lymphocytes. Combined treatment with vorinostat and 5′-DFUR resulted in a synergistic antiproliferative effect and increased apoptotic cell death in vitro. This latter effect was impaired in cells where TP was knocked. In vivo, vorinostat plus capecitabine potently inhibited tumour growth, increased apoptosis and prolonged survival compared with control or single-agent treatments.

Conclusions:

Overall, this study suggests that the combination of vorinostat and capecitabine is an innovative antitumour strategy and warrants further clinical evaluation for the treatment of CRC.     

Effectiveness of chest radiography,lung ultrasound and thoracic computed tomography in the diagnosis of congestive heart failure

Hydrostatic pulmonary edema is as an abnormal increase in extravascular water secondary to elevated pressure in the pulmonary circulation, due to congestive heart failure or intravascular volume overload. Diagnosis of hydrostatic pulmonary edema is usually based on clinical signs associated to conventional radiography findings. Interpretation of radiologic signs of cardiogenic pulmonary edema are often questionable and subject. For a bedside prompt evaluation, lung ultrasound (LUS) may assess pulmonary congestion through the evaluation of vertical reverberation artifacts, known as B-lines. These artifacts are related to multiple minimal acoustic interfaces between small water-rich structures and alveolar air, as it happens in case of thickened interlobular septa due to increase of extravascular lung water. The number, diffusion and intensity of B lines correlates with both the radiologic and invasive estimate of extravascular lung water. The integration of conventional chest radiograph with LUS can be very helpful to obtain the correct diagnosis. Computed tomography (CT) is of limited use in the work up of cardiogenic pulmonary edema, due to its high cost, little use in the emergencies and radiation exposure. However, a deep knowledge of CT signs of pulmonary edema is crucial when other similar pulmonary conditions may occasionally be in the differential diagnosis.     

Perineural arachnoidal gliomatosis: case report

Gliomas are the most common infiltrative neoplasms of the optic nerve and can present as two distinct growth patterns: intraneural glial proliferation and perineural arachnoidal gliomatosis (PAG). It has been suggested that perineural arachnoidal gliomatosis is seen almost exclusively in the setting of neurofibromatosis type 1 (NF1). We describe a child with perineural arachnoidal gliomatosis occurring without neurofibromatosis type 1, supported by both radiographic and histological findings. A 4-year-old female without neurofibromatosis type 1 presented with rapidly progressive right-sided proptosis. Magnetic resonance imaging (MRI) revealed an enhancing fusiform intraconal lesion, which was hypointense on T1 and hyperintense on T2-weighted images: characteristic of perineural arachnoidal gliomatosis, the optic nerve was visualized coursing the tumor. Histopathologic study was consistent with perineural arachnoidal gliomatosis. Perineural arachnoidal gliomatosis can develop independent of neurofibromatosis type 1, as demonstrated by this case.