The Effect of Basic Fibroblast Growth Factor on the Reversion of Omental Adipocytes from Lean and Obese Patients

Background: this study was designed to characterize some of the biochemical and molecular genetic changes during reversion of human fat cells. Methods: mature adipocytes were isolated from greater omental fat tissue of eight lean and 14 massively obese persons by established methodology. Results: at day 7 of adherence to Leighton tubes, there was appreciable depletion of triacylglycerol, as well as assumption of an elongated contour. Relatedly, there was an increase in the expression of β-actin mRNA and a significant decrease in the specific activity of cytosolic glycerophosphate dehydrogenase. The decrement in the specific activity of glycerophosphate dehydrogenase, after 7 days in culture, was significant at p < 0.001. Basic fibroblast growth factor at 10 ngml^-1 accelerated significantly (p < 0.03) the decrease in the specific activity of glycerophosphate dehydrogenase in adipose cells from lean subjects. In contrast, basic fibroblast growth factor had no significant influence on cells from massively obese persons. Conclusion: such resistance may contribute to the intractability of massive obesity.     

Interlaboratory comparison of HER-2 oncogene amplification as detected by chromogenic and fluorescence in situ hybridization.

PURPOSE: Chromogenic in situ hybridization (CISH) is a new modification of the fluorescence in situ hybridization (FISH) technique for detection of oncogene amplification in archival tumor samples. In CISH, the oncogene probe is detected using a peroxidase reaction, allowing use of transmitted light microscopy. We compared detection of HER-2/neu amplification by CISH with a Food and Drug Administration-approved two-color FISH test in an interlaboratory setting. EXPERIMENTAL DESIGN: Formalin-fixed paraffin-embedded tumor samples from 197 breast cancers were analyzed for HER-2 amplification by CISH. Two-color FISH (PathVysion) CISH of 17 centromere was done if the observer considered it necessary to ascertain amplification status in tumors with borderline HER-2 CISH copy numbers. RESULTS: Paired CISH/FISH results were available from 192 (97%) of 197 cases, no clear difference in success rates of either method was observed. Centromere 17 CISH was considered necessary in seven tumors. CISH and two-color FISH results were concordant in 180 cases (93.8%). There were 92 and 88 tumors found HER-2 amplified and nonamplified, respectively, by both methods. Eight tumors were amplified by CISH but not by FISH, and four tumors exhibited the opposite condition (kappa coefficient 0.875). In 7 of 12 cases differences between the two methods could have related to a lack of CISH chromosome 17 information. The remaining cases were explained by difficult histology (ductal carcinoma in situ, poor representativity, dense lymphocytic infiltration, or intratumoral heterogeneity). CONCLUSIONS: These results indicate that CISH could provide an accurate and practical alternative to FISH for clinical diagnosis of HER-2/neu oncogene amplification in archival formalin-fixed breast cancer samples.     

[18F] FDG PET in Gastric Non-Hodgkin's Lymphoma

The possibility of using [¹⁸F] FDG PET for assessment of tumor extension in primary gastric non-Hodgkin's lymphoma (NHL) was studied in 8 patients (6 high-grade and 2 Iow-grade, one of the MALT type) and in a control group of 7 patients (5 patients with NHL without clinical signs of gastric involvement, 1 patient with NHL and benign gastric ulcer and 1 patient with adenocarcinoma of the stomach). All patients with gastric NHL and the two with benign gastric ulcer and adenocarcinoma, respectively, underwent endoscopy including multiple biopsies for histopathological diagnosis. All patients with high-grade and one of the two with low-grade NHL and the patient with adenocarcinoma displayed high gastric uptake of [¹⁸F] FDG corresponding to the pathological findings at endoscopy and/or CT. No pathological tracer uptake was seen in the patient with low-grade gastric NHL of the MALT type. In 6/8 patients with gastric NHL, [¹⁸F] FDG PET demonstrated larger tumor extension in the stomach than was found at endoscopy, and there was high tracer uptake in the stomach in two patients who were evaluated as normal on CT. [¹⁸F] FDG PET correctly excluded gastric NHL in the patient with a benign gastric ulcer and in the patients with NHL without clinical signs of gastric involvement. Although the experience is as yet limited, [¹⁸F] FDG PET affords a novel possibility for evaluation of gastric NHL and would seem valuable as a complement to endoscopy and CT in selected patients, where the technique can yield additional information decisive for the choice of therapy.     

Spectacle use and reduced unaided vision in third grade students: a comparative study in different educational settings

Background: The development of myopia is influenced by hereditary factors, environmental factors and geneenvironment interaction. Reading and near‐work activity are associated with myopia and myopic progression. This study sought to determine and compare the prevalence of reduced unaided vision and spectacle use among third grade Israeli students from three different educational settings. Method: A sample of 917 students (mean age 8.5 years, range seven to 10 years) was drawn from the three Israeli educational streams: secular, Orthodox and ultra‐Orthodox. Children in the ultra‐Orthodox education pathway begin studying at the age of three years and their daily reading involves sustained near work with increased accommodative effort accompanied by head‐rocking movements. Reduced distance vision was used to indicate the likely development of or an increase in the amount of myopia. Spectacle lenses were measured to determine the prevalence of myopia. Results: Of the 917 students studied, 103 (11.2 per cent) wore spectacles (14.2 per cent of the males and eight per cent of the females); 82.5 per cent of those who wore spectacles were myopic. Males from ultra‐Orthodox schools had the highest rate of reduced unaided vision (72.5 per cent) compared with males from secular schools (27.3 per cent), males from Orthodox schools (59.3 per cent) or with females from all three groups (average of 34.8 per cent, p < 0.0001, chi squared). Males had a higher rate of reduced unaided vision, especially in the Orthodox and ultra‐Orthodox schools. Conclusions: Our study suggests that Jewish ultra‐Orthodox males have a higher prevalence and degree of myopia. The study habits of young children, including exposure to prolonged near tasks, high accommodative demands and possibly optical defocus induced by body sway, may contribute to the development of myopia.     

Interactions of chronic lead exposure and intermittent stress: consequences for brain catecholamine systems and associated behaviors and HPA axis function.

Elevated lead (Pb) burden and high stress levels are co-occurring risk factors in low socioeconomic status (SES) children. Our previous work demonstrated that maternal Pb exposure can permanently alter hypothalamic-pituitary-adrenal (HPA) axis function and responsivity to stress challenges in offspring. The current study sought to determine the consequences of chronic Pb exposures initiated later in development combined with variable intermittent stress challenges. Male rats were exposed chronically from weaning to 0, 50, or 150 ppm Pb acetate drinking solutions (producing blood Pb levels of <5, 9-15, and 23-27 mug/dl, respectively). Pb itself decreased basal plasma corticosterone, with greater effects at 50 than 150 ppm; 150 ppm reduced both cytosolic and nuclear glucocorticoid receptor binding. Responsivity to stress challenges including novelty, cold, and restraint, was measured as changes in Fixed Interval (FI) schedule-controlled behavior in a subset of rats within each group. FI performance was modified by novelty stress only in Pb-treated rats, whereas cold and restraint stress effects were comparable across groups. Novelty elevated corticosterone equivalently across groups, but cold stress markedly increased corticosterone only in Pb-treated groups. The pattern of Pb-induced changes in serotonin (5-HT) or its metabolite 5-HIAA in frontal cortex, nucleus accumbens, striatum, and hypothalamus resembled that observed for basal corticosterone levels indicating a relationship between these variables. In addition to suggesting the potential for HPA axis-mediated effects of Pb on the central nervous system, these findings also raise questions about whether single chemicals studied in isolation from other relevant risk factors can adequately identify neurotoxic hazards.     

Vascular modulation through exercise improves chemotherapy efficacy in Ewing sarcoma

Recent studies in mouse models of cancer have shown that exercise improves tumor vascular function, thereby improving chemotherapy delivery and efficacy. However, the mechanisms underlying this improvement remain unclear and the effect of exercise on Ewing sarcoma (ES), a pediatric bone and soft tissue cancer, is unknown. The effect of exercise on tumor vascular hyperpermeability, which inversely correlates with drug delivery to the tumor, has also not been evaluated. We hypothesized that exercise improves chemotherapy efficacy by enhancing its delivery through improving tumor vascular permeability. We treated ES‐bearing mice with doxorubicin with or without moderate treadmill exercise. Exercise did not significantly alter ES tumor vessel morphology. However, compared to control mice, tumors of exercised mice had significantly reduced hyperpermeability, significantly decreased hypoxia, and higher doxorubicin penetration. Compared to doxorubicin alone, doxorubicin plus exercise inhibited tumor growth more efficiently. We evaluated endothelial cell sphingosine‐1‐phosphate receptors 1 and 2 (S1PR1 and S1PR2) as potential mediators of the improved vascular permeability and increased function afforded by exercise. Relative to tumors from control mice, vessels in tumors from exercised mice had increased S1PR1 and decreased S1PR2 expression. Our results support a model in which exercise remodels ES vasculature to reduce vessel hyperpermeability, potentially via modulation of S1PR1 and S1PR2, thereby improving doxorubicin delivery and inhibiting tumor growth more than doxorubicin alone does. Our data suggest moderate aerobic exercise should be tested in clinical trials as a potentially useful adjuvant to standard chemotherapy for patients with ES.     

Shoulder dystocia: a comparison of patients with and without diabetes mellitus

Background: The study was aimed to compare pregnancies complicated with shoulder dystocia, of patients with and without diabetes mellitus. Methods: A comparison of all singleton, vertex, term deliveries between the years 1988–1999, complicated with shoulder dystocia with and without diabetes mellitus was performed. Statistical analysis was done using receiver operating characteristic curve analysis. Results: Using a receiver operating characteristic curve analysis, the area under the curve for birth weight was 0.92 (95% CI 0.90–0.93). However, for birth weight of 4,000 g the sensitivity was only 56% with specificity of 95%. While comparing shoulder dystocia between patients with (n=38) and without diabetes mellitus (n=207), neonates of the diabetic patients were significantly heavier (mean birth weight 4,244.2±515.1 vs. 4,051.6±389.5; P=0.008) and had higher rate of Apgar scores lower than 7 at 1 min (50.0% vs. 25.9%; P=0.030), but not at 5 min (2.6% vs. 2.0%; P=0.083) when compared to the non-diabetic group. No significant differences were noted regarding perinatal mortality between the groups (0% vs. 4.3%; P=0.362). Conclusions: The newborn of the diabetic mother complicated with shoulder dystocia does not appear to be at an increased risk for perinatal morbidity compared with the newborn of the non-diabetic mother. Presented in part at the Society for Gynecologic Investigation 50th Annual Scientific Meeting, Washington, DC, 27–30 March 2003.     

Prevalence of Chikungunya,Dengue and Zika viruses in blood donors: a systematic literature review and meta-analysis

BackgroundBlood transfusion centres should understand the epidemiology of emerging diseases that are transmissible through the transfusion of blood components. The risk of transmission of arboviruses through this route has become apparent in recent years. The aim of our study is to summarise the reported prevalence (viraemic rate, seroprevalence and/or antigen detection) of Chikungunya (CHIKV), Dengue (DENV) and Zika (ZIKV) viruses in blood donors according to screening test used and world region.Materials and methodsWe conducted a systematic literature review and meta-analysis having searched for information in the main bibliographic databases (MEDLINE, Embase, and Scopus). The prevalence for each of the viruses was calculated according to the screening test used and geographic location.ResultsWe included 18 records on CHIKV, 71 on DENV, and 27 on ZIKV. The highest prevalences of RNA for CHIKV were 1.9% in Puerto Rico (2014), 1.0% in Thailand (2009), and 1.0% in French Polynesia (2014–15). The highest prevalences of RNA for DENV were 5.5% in Saudi Arabia (2015–16), 2.3% in Madeira, Portugal (2012–13), and 0.6% in Brazil (2012). The highest prevalences of RNA for ZIKV were 2.8% in French Polynesia (2013–14), 2.7% in Brazil (2015–16), and 1.8% in Martinique (2016). Overall seroprevalence, as assessed by IgG antibodies, was 21.6% for CHIKV, 24.0% for DENV, and 5.1% for ZIKV.DiscussionOur study shows a high proportion of donors who are viraemic and asymptomatic, especially during outbreaks, with prevalences surpassing 5% for DENV, 1% for CHIKV, and 2% for ZIKV. These data confirm a clear threat to blood transfusion safety. The elevated seroprevalence for these three arboviruses is also indicative of their wide circulation in populations, correlating with an increased risk of infected but asymptomatic donors. Health centres and institutions must address this threat, especially in tropical regions where the biggest outbreaks occur.