A reappraisal of the utility of somatostatin receptor scintigraphy in patients with ectopic adrenocorticotropin Cushing's syndrome

Ectopic ACTH hypersecretion is a rare cause of Cushing's syndrome. Bronchial carcinoids are the most common neoplasms causing the occult ectopic ACTH syndrome (EAS). Localization of these tumors is often difficult. The diagnostic utility of somatostatin receptor scintigraphy (SRS) in EAS has been studied in a limited number of patients with conflicting results. Herein we report our experience with 12 consecutive cases. Histological confirmation was obtained in nine patients, the majority being bronchial carcinoids. Among the seven patients with histologically confirmed bronchial carcinoids, SRS was performed in six patients. In three patients SRS correctly localized a bronchial carcinoid tumor at presentation. In the remaining three it became positive after 8, 22, and 27 months during follow-up. In two patients SRS was positive without any finding in the corresponding conventional imaging study. In two patients positive computed tomography/magnetic resonance imaging preceded SRS localization. There was no false positive SRS. Among three patients with highly suspected EAS, SRS was positive in one. Both patients with EAS due to medullary thyroid carcinoma had focal positive uptake. In summary, in this study a substantial number of patients had positive tumor localization by SRS. Therefore, SRS is a useful tool in the evaluation of patients with EAS.     

Cryoglobulinemia and progression of fibrosis in chronic HCV infection: cause or effect?

OBJECTIVES: Mixed cryoglobulinemia (MC) is the most common extrahepatic manifestation of HCV infection. The aim of this study is to determine the prevalence of MC in HCV infected Greek patients and to identify if it is associated with liver histology or the mode of HCV transmission. METHODS: One hundred and twenty-six patients with chronic HCV infection were evaluated for the presence of serum cryoglobulins, autoantibodies and viral markers. One hundred and eighteen of them underwent liver biopsy and each specimen was evaluated according to the grading and staging system described by Ishak et al. RESULTS: Cryoglobulins were detected in 37/126 (29.4%) HCV patients and cryocrit values ranged between 0.5 and 6.5%. Only two patients presented clear clinical manifestations of MC. In patients with MC, a higher grading (6.40+/-2.06 vs. 5.27+/-2.55, p=0.013) and staging score (3.71+/-1.45 vs. 2.83+/-1.84, p=0.007) was noted in liver biopsy compared to those without MC. Logistic regression analysis identified staging score (OR, 1.33; CI, 1.06-1.66, p=0.015) as the only independent variable associated with cryoglobulinemia. Correlation between the presence of cryoglobulins and the mode of HCV transmission was not found. CONCLUSIONS: Greek patients with chronic HCV infection have high prevalence of cryoglobulinemia. A clear association between the presence of serum cryoglobulins and staging score of chronic hepatitis was found, with no difference in patients' age or the duration of infection. It is possible that cryoglobulinemia results in more rapid hepatic fibrosis in HCV infected patients.     

Adolescents' reactions after a wildfire disaster in Greece

This cross-sectional study examined the factors associated with higher levels of posttraumatic stress disorder (PTSD) and depression symptoms in 1,468 adolescents, 6 months after a wildfire. The rate of probable PTSD was 29.4% and 20% for probable depression. Findings on predisaster, disaster-related, and postdisaster factors revealed that disaster-related factors-specifically objective and perceived threat to self and others-were associated with symptoms of PTSD but not depression. Predisaster life events, postdisaster losses, and escape-oriented coping strategies were associated with higher levels of both PTSD and depression symptoms, while control-oriented coping and perceived social support were differentially associated with symptoms of and depression. Findings have implications for the assessment and treatment of traumatized and depressed adolescents after a disaster.     

DNA methylation changes measured in pre‐diagnostic peripheral blood samples are associated with smoking and lung cancer risk

DNA methylation changes are associated with cigarette smoking. We used the Illumina Infinium HumanMethylation450 array to determine whether methylation in DNA from pre‐diagnostic, peripheral blood samples is associated with lung cancer risk. We used a case‐control study nested within the EPIC‐Italy cohort and a study within the MCCS cohort as discovery sets (a total of 552 case‐control pairs). We validated the top signals in 429 case‐control pairs from another 3 studies. We identified six CpGs for which hypomethylation was associated with lung cancer risk: cg05575921 in the AHRR gene (p‐value_pooled = 4 × 10^?17), cg03636183 in the F2RL3 gene (p‐value_pooled = 2 × 10 ^{? 13}), cg21566642 and cg05951221 in 2q37.1 (p‐value_pooled = 7 × 10^?16 and 1 × 10^?11 respectively), cg06126421 in 6p21.33 (p‐value_pooled = 2 × 10^?15) and cg23387569 in 12q14.1 (p‐value_pooled = 5 × 10^?7). For cg05951221 and cg23387569 the strength of association was virtually identical in never and current smokers. For all these CpGs except for cg23387569, the methylation levels were different across smoking categories in controls (p‐values_{heterogeneity} ≤ 1.8 x10 ^{? 7}), were lowest for current smokers and increased with time since quitting for former smokers. We observed a gain in discrimination between cases and controls measured by the area under the ROC curve of at least 8% (p‐values ≥ 0.003) in former smokers by adding methylation at the 6 CpGs into risk prediction models including smoking status and number of pack‐years. Our findings provide convincing evidence that smoking and possibly other factors lead to DNA methylation changes measurable in peripheral blood that may improve prediction of lung cancer risk.     

Enhanced mRNA expression of tissue inhibitor of metalloproteinase-1 (TIMP-1) in breast carcinomas is correlated with adverse prognosis

Tissue inhibitor of metalloproteinase-1 (TIMP-1) has emerged as a multifunctional protein with the contrasting activities of inhibiting tissue-degrading enzymes and promoting cellular growth. In an attempt to elucidate the clinical significance of TIMP-1 in breast cancer, the expression of TIMP-1 mRNA was evaluated in 117 invasive breast carcinomas by mRNA in situ hybridization, in correlation with clinicopathological parameters, immunohistochemical prognostic factors (Ki-67, c-erb-B-2, bcl-2) and clinical outcome. TIMP-1 was detected in stromal cells in areas within the tumours and at the tumour margin. High TIMP-1 mRNA expression in the marginal portion of the tumours was significantly correlated with lymph node metastasis (p<0.05) and c-erbB-2 expression (p<0.05). On the other hand, increased TIMP-1 mRNA expression within the tumours showed a statistically significant correlation with ER detection (p<0.01). Multivariate analysis revealed worse survival for patients with high TIMP-1 mRNA expression in the marginal portion of the tumours; the subgroup of these patients co-expressing high levels of TIMP-1 mRNA within the tumours as well had even worse survival (p=0.042). In conclusion, our data support the multifunctional role of TIMP-1, particularly its growth-promoting activity, on the basis of its significant correlation with lymph node metastasis and adverse prognosis. In addition to the latter property, a probable association of TIMP-1 with tumour cell differentiation is suggested by its topographical correlation with ER detection.     

Retention of styrene following controlled exposure to constant and fluctuating air concentrations

An experiment was designed to determine whether the respiratory retention of sytrene vapor, as estimated from measurements of end-exhaled air, was the same during periods of both constant and fluctuating exposure. Six human subjects were exposed to styrene inside an experimental chamber. A computer-controlled system was used to generate time-varying air concentrations of styrene over 4–5 h in both multistep sequences of constant exposure (four subjects exposed to 15–99 ppm. of styrene in 100-min steps) and fluctuating patterns representative of occupational exposures (two subjects exposed to mean concentrations of styrene of 50 ppm). In the latter case, lognormally distributed exposures, which fit one of two first-order autoregressive models, were generated at intervals of 2.5 min. It was found that the concentration of styrene in end-exhaled air was reduced by about half if the subject inhaled one to three breaths of clean air prior to sampling. This suggests that significant amounts of styrene were desorbed from the lining of the lungs during the initial exhalation. The retention of styrene vapor during constant exposures was 0.935 and was independent of the level. During each of the two sets of fluctuating exposure the retention of sytrene was also constant and was independent of both the variance and the autocorrelation coefficient. However, the retention of styrene during fluctuating exposure (estimates ranged from 0.957 to 0.973) was significantly higher than that observed during the constant exposures. It is speculated that the difference in retention between the constant and the fluctuating exposure regimens is related to non-steady-state behavior of styrene in the richly perfused tissues, as suggested by Opdam and Smolders (1986) regarding tetrachloroethylene exposure.     

Expression of tissue inhibitor of matrix metalloproteinases (TIMP)-3 protein in invasive breast carcinoma: Relation to tumor phenotype and clinical outcome

Introduction  

Our aim was to study the expression pattern of tissue inhibitor of metalloproteinases (TIMP)-3 protein in invasive breast carcinoma, and its clinicopathological and prognostic value as well as its relation to markers indicative of the tumor phenotype.     

Why Reject a Sensory Imagery Theory of Control Consciousness?

Mandik (2010) defends a motor theory of control consciousness according to which nonsensory states, like motor commands, directly contribute to the awareness we have of ourselves as being in control of our actions. Along the way, he argues that his theory is to be preferred over Prinz’s (2007) sensory imagery theory, which denies that nonsensory states play any direct role in the generation of control consciousness. I argue that Mandik’s criticisms of Prinz’s theory fall short, but that nonetheless there are reasons to favor a motor theory of control consciousness over a sensory imagery theory.     

Enamel matrix derivative and systemic antibiotics as adjuncts to non-surgical periodontal treatment: biologic response

BACKGROUND: Short-term clinical observations suggest an anti-inflammatory effect of enamel matrix derivative (EMD). The purpose of this study was to evaluate the anti-inflammatory capacity of EMD, used as an adjunct to non-surgical periodontal treatment of deep lesions in chronic periodontitis patients, by monitoring inflammatory markers in gingival crevicular fluid (GCF). METHODS: Sixteen subjects were randomly assigned to treatment with EMD or placebo in contralateral dentition areas. Half of the subjects received 250 mg metronidazole and 375 mg amoxicillin three times a day for 7 days; the other half received a placebo. GCF samples were collected from one interproximal lesion in each of the contralateral quadrants before treatment and after 10 days and 2, 6, and 12 months. Total protein content was determined according to the Bradford method. Myeloid-related protein (MRP) 8/14 and interleukin (IL)-1beta were analyzed quantitatively by enzyme-linked immunosorbent assay (ELISA), and elastase activity was determined using a low molecular weight fluorogenic substrate. RESULTS: No significant differences were observed between sites treated with or without EMD for any biochemical parameter. Two months after treatment, subjects treated with antibiotics exhibited less clinical signs of inflammation. Furthermore, these subjects had lower MRP 8/14 levels only at day 10 compared to those receiving the placebo. For total protein, IL-1beta, and elastase, no statistically significant differences were noted for subjects with or without antibiotic therapy at any time point. CONCLUSIONS: Improved healing of the soft tissues has been noted clinically in non-surgically treated sites in subjects treated with antibiotics. The expression of inflammatory mediators in GCF corroborated this finding only in part. EMD did not seem to further affect the expression of inflammatory mediators.