Randomized prospective study comparing high-dose-rate intraluminal brachytherapy (HDRILBT) alone with HDRILBT and external beam radiotherapy in the palliation of advanced esophageal cancer

PURPOSE: HDRILBT is one of the best methods of palliation for advanced esophageal cancer (AEC) by improving dysphagia-free survival (DFS) and overall survival (OS). This study examines if the addition of EBRT would further improve the outcome by improving DFS in AEC. METHODS AND MATERIALS: Patients with inoperable AEC were entered into a randomized prospective study. HDRILBT of 16 Gy/2 fractions/3 days was given initially to all patients. Following treatment, patients were randomized to receive no further treatment (Group A) or additional EBRT of 30 Gy/10 fractions/2 weeks (Group B) and were followed for 1 year. Statistical analysis of the data was done using the SAS statistical software package (SAS Institute, Cary, NC). Prognostic variables were analyzed using the chi(2) and log-rank tests and survival curves were drawn using the Kaplan-Meier method. Multivariate survival analysis was done using the Cox proportional hazards model. RESULTS: Sixty patients were entered into the study. Patient and tumor characteristics were comparable among the groups. Of 30 patients in Group B, 2 refused additional EBRT (no dysphagia). At 6 months, >50% had DFS in both groups and this was comparable. There was no difference statistically (p >0.05) in the DFS and OS between the two groups at the end of 12 months. Median survival for Group A was 7.23 months and 7.5 months for Group B. Additional EBRT did not improve DFS or OS. Eleven patients developed strictures related to radiotherapy and were dilated successfully (Group A, 7; Group B, 4; p >0.05). Four patients had progressive luminal disease which progressed to fistula (Group A, 3; Group B, 1; p >0.05). There was no effect of any patient or treatment parameter on DFS. Presenting weight and ECOG score had an impact on OS. CONCLUSIONS: From the preliminary analysis, additional EBRT to HDRILBT does not improve DFS or outcomes in inoperable AEC.     

Cardiovascular disease risk factors among children of different socioeconomic status in Istanbul,Turkey: Directions for public health and nutrition policy

Objectives

The aim of the current study was to examine the influence of socioeconomic status (SES) on physiological (lipid profile, obesity indices) and behavioral (dietary habits, physical activity) cardiovascular disease (CVD) risk factors among primary schoolchildren in Istanbul.

Design

Cross sectional study.

Setting

One private school and two public schools from different SES districts in Istanbul.

Participants

510 randomly selected children aged 12 and 13 years old (257 boys, 253 girls).

Results

The prevalence of overweight (15.2%) and the energy intake (p < 0.001 and p < 0.05 for boys and girls respectively) were found to be higher for the middle/ high SES group for both genders. Regarding biochemical indices, middle/ high SES children had higher values of High Density Lipoprotein-cholesterol (HDL-C) (p < 0.001 and p < 0.05 for boys and girls respectively) and lower values of TC/HDL-C ratio and LDL-C/HDL-C ratio (p < 0.05 and p < 0.001 for boys and girls respectively). This could be attributed to the higher physical activity levels observed for middle/ high SES children (p < 0.001).

Conclusion

The findings of the current study revealed a coexistence of both overweight and higher energy intake in middle/ high SES children, as well as a coexistence of underweight and lower physical activity levels in low SES children. These observations should guide the public health policy in developing appropriate intervention strategies to efficiently tackle these health and social issues early in life.

     

Discovery of positive allosteric modulators for the metabotropic glutamate receptor subtype 5 from a series of N-(1,3-diphenyl-1H- pyrazol-5-yl)benzamides that potentiate receptor function in vivo

This report describes the discovery of the first centrally active allosteric modulators of the metabotropic glutamate receptor subtype 5 (mGluR5). Appropriately substituted N-(1,3-diphenyl-1H-pyrazol-5-yl)benzamides (e.g., 8) have been identified as a novel class of potent positive allosteric modulators of mGluR5 that potentiate the response to glutamate. An iterative analogue library synthesis approach provided potentiators with excellent potency and selectivity for mGluR5 (vs mGluRs 1-4, 7, 8). Compound 8q demonstrated in vivo proof of concept in an animal behavior model where known antipsychotics are active, supporting the development of new antipsychotics based on the NMDA hypofunction model for schizophrenia.     

Hippocampal damage in mouse and human forms of systemic autoimmune disease

Systemic lupus erythematosus (SLE) is frequently accompanied by neuropsychiatric (NP) and cognitive deficits of unknown etiology. By using autoimmune MRL-lpr mice as an animal model of NP-SLE, we examine the relationship between autoimmunity, hippocampal damage, and behavioral dysfunction. Fluoro Jade B (FJB) staining and anti-ubiquitin (anti-Ub) immunocytochemistry were used to assess neuronal damage in young (asymptomatic) and aged (diseased) mice, while spontaneous alternation behavior (SAB) was used to estimate the severity of hippocampal dysfunction. The causal relationship between autoimmunity and neuropathology was tested by prolonged administration of the immunosuppressive drug cyclophosphamide (CY). In comparison to congenic MRL +/+ controls, SAB acquisition rates and performance in the "reversal" trial were impaired in diseased MRL-lpr mice, suggesting limited use of the spatial learning strategy. FJB-positive neurons and anti-Ub particles were frequent in the CA3 region. Conversely, CY treatment attenuated the SAB deficit and overall FJB staining. Similarly to mouse brain, the hippocampus from a patient who died from NP-SLE showed reduced neuronal density in the CA3 region and dentate gyrus, as well as increased FJB positivity in these regions. Gliosis and neuronal loss were observed in the gray matter, and T lymphocytes and stromal calcifications were common in the choroid plexus. Taken together, these results suggest that systemic autoimmunity induces significant hippocampal damage, which may underlie affective and cognitive deficits in NP-SLE.     

Factors affecting dental job satisfaction: a cross-sectional survey in Turkey

In this cross-sectional study, a randomly selected group of dentists (n = 855) from nine provinces of Turkey were interviewed for their levels of intrinsic, extrinsic, and overall job satisfaction. The proportion of overall job satisfaction was computed as the proportion of dentists who had mean general satisfaction scores > or = 4 on a 5-point, Likert-type scale and was found to be 40.8% for the sample as a whole. The significant factors that affected overall satisfaction were age, the type of social insurance possessed, income level, the presence of dental auxiliaries, and the number of patients examined per day. Multivariate analysis of the data revealed that the type of social insurance, the amount of monthly income, and the number of patients examined per day were the most common and statistically significant predictors of intrinsic, extrinsic, and overall satisfaction in Turkish dentists.     

An evaluation of current shigellosis treatment

Shigellosis or bacillary dysentery, characterised by the passage of frequent loose stools mixed with blood and mucous, is caused by Shigella spp. which can be subdivided into four serotypes, namely, S. sonnei, S. boydii, S. flexneri and S. dysenteriae. S. dysenteriae type 1 produces severe dysentery and may be associated with many complications like leukaemoid reaction and haemolytic-ureamic syndrome. It is known to produce protracted epidemics and pandemics and is usually multi-drug resistant. Antibiotics are the mainstay of therapy of all cases of shigellosis. Antibiotics such as tetracycline, ampicillin and co-trimoxazole, were previously highly effective. Newer fluoroquinolones such as norfloxacin, ciprofloxacin, ofloxacin, azithromycin and ceftriaxone are effective. Although single dose of norfloxacin 800 mg and ciprofloxacin 1 g have been shown to be effective, they are currently less effective against S. dysenteriae type 1 infection. Oral rehydration salt should be given concurrently to prevent or correct dehydration. Antimotility agents are contraindicated. Feeding during and after shigellosis is emphasised. Hand-washing practices with plenty of water and soap help to prevent the transmission of infection from person to person. A search is on for an effective vaccine against shigella.     

Mechanisms contributing to the vaso-active effects of prilocaine in human skin

We investigated the roles of the endothelial nitric oxide and cyclo-oxygenase pathways in mediating the vasoactivity of prilocaine in the skin. We injected prilocaine 1% intradermally into forearm skin of 10 healthy, male subjects. Nitric oxide synthesis was inhibited at a second site by co-injecting prilocaine with l-NAME 1%. We then repeated the injections while blocking the cyclo-oxygenase pathway with aspirin (4 x 600 mg). We measured blood flow responses to the injections using laser Doppler imaging. We found that, after the traumatic effects of injection had subsided, l-NAME reduced the vascular response to prilocaine by a third (p = 0.012), indicating an influence specifically on the drug response. Aspirin had no effect on the response (p = 0.588). We conclude that the vasoactive effects of prilocaine in human skin are mediated partly through the release of endothelial nitric oxide and, although other mechanisms might also be involved, the cyclo-oxygenase pathway does not appear to play a role.     

Preliminary report on the effect of brachytherapy on expression of p53, bc1-2 and apoptosis in squamous cell carcinoma of the oesophagus

Pre-brachytherapy biopsies and post-brachytherapy oesophagectomy specimens of 10 patients with early squamous cell carcinoma of the middle third of the oesophagus were examined for the expression of p53, bcl-2 and apoptosis using immunohistochemical markers. There was no expression of p53 in one patient in both pre- and post-brachytherapy specimens. In 8 patients, p53 staining was strongly positive (3+) with approximately 50% or more cells, and with diffuse and no specific pattern in the pre-brachytherapy biopsies. The tumour areas of the post-brachytherapy specimens of this group showed strong 3+ positivity with p53 (10-50% positive cell count), with the pattern being focal and peripheral in the tumour islands. The centre of the tumour islands showed necrosis and/or keratinisation. In one patient, the pre-brachytherapy biopsy showed expression of p53 while the post-brachytherapy specimen was negative. bcl-2 expression in both pre- and post-brachytherapy was equivocal and inconclusive in both the pre- and post-brachytherapy specimens. Apoptosis was negative in all the pre- and post-brachytherapy tissue sections in the presence of positive controls. Brachytherapy does not cause cell death by apoptosis but by necrosis and maturation of the cells into better differentiated cells, which is caused by OH free radical, and induction of the keratin gene respectively. It is possible that brachytherapy may cause destruction of cells containing wild-type p53, while mutant p53 in cells located at the tumour periphery escape the effect of brachytherapy. This may be responsible for the high incidence of local recurrence and distant metastasis in oesophageal cancer treated with radiotherapy. There is no effect of brachytherapy on bcl-2 expression in oesophageal cancer.