Frontal bilateral megalencephaly: fetal and autopsy MR evaluation of an unclassified malformation

OBJECTIVE: To describe an unreported brain malformation with in utero onset. METHODS: A 21-weeks-of-gestational-age fetus underwent prenatal MR imaging because of macrocephaly detected by ultrasound. Prenatal MR imaging revealed a complex brain malformation. At 22 weeks of GA, pregnancy was terminated; an MR autopsy study was also performed. RESULTS: MR imaging revealed frontal bilateral megalencephaly and malformation of cortical development, suggesting polymicrogyria. These findings do not fit into any of the known megalencephalic syndromes. CONCLUSIONS: To our knowledge, this is a previously unreported malformation. Fetal and autoptic MR examination have been the best tools in understanding this complex brain pathology, allowing a more complete genetic counseling.     

Antihypertensive and renal effects of orally administered verapamil

Summary In 12 in-patients with moderate uncomplicated hypertension, maintained on constant sodium intake for 15 days, single-blind oral administration of verapamil 80–160 mg t. i. d. for 10 days had a significant antihypertensive effect: in the supine position systolic blood pressure decreased from 177±5 to 150±3 mmHg, and diastolic pressure from 111±3 to 96±2 mmHg; standing values were similarly lowered from 171±7 to 143±4 mmHg, systolic, and from 118±4 to 97±2 mmHg, diastolic. The heart rate did not show any significant change (from 79±3 to 77±2 beats/min, supine, and from 92±3 to 87±3 beats/min, upright). The antihypertensive effect was uniform throughout the day, being similar 2, 3, 6 and 8 h after administration of a dose. Dynamic exercise (75–100 watts on a cycle-ergometer) caused identical increases in arterial pressure and heart rate on the last day of placebo and again on the last day with verapamil, but the peak levels of systolic pressure reached during exercise were lower after verapamil than with placebo, because of the lower blood pressure before exercise. Reduction of arterial pressure by verapamil was not accompanied by increased plasma renin activity, or by renal retention of sodium and water: there was a small increase in sodium excretion, at least during the first days of verapamil administration (from 107±15 to 113±15 mEq Na⁺/day), and a slight significant reduction in body weight (from 74.2±3.7 to 73.5±3.7 kg). It is concluded that oral administration of verapamil significantly lowers blood pressure without simultaneously inducing cardiac stimulation, renin secretion or salt and water retention.     

Profile of short-chain fatty acids and rectal proliferation in rats fed sucrose or cornstarch diets.

Rats were fed high fat (231 g/kg diet), low calcium (1.3 g/kg diet), low cellulose (20 g/kg diet) diets in which carbohydrates were represented by sucrose or starch (460 g/kg diet). A subgroup of animals was treated with 1,2-dimethylhydrazine (DMH) twice, 4 and 8 d before the beginning of the dietary treatments. Animals fed the starch diet, compared with those fed the sucrose diet, had higher concentrations of cecal and fecal short-chain fatty acids and a significantly lower acetic acid:butyric acid ratio in the cecal contents at d 105. Ratios were 14.7 +/- 1.7 and 6.8 +/- 0.4 for rats fed the sucrose and starch diets, respectively (P less than 0.01). Cecal pH was significantly lower in animals fed the starch diet for 105 d. At d 105, rectal proliferation was lower in rats fed the starch diet (labeled cells/crypt were 7.89 +/- 0.56 and 3.57 +/- 0.40 for rats fed the sucrose and starch diets, respectively, P less than 0.01); at d 30 the effect of starch on proliferation was evident in controls but not in DMH-treated rats. Rectal proliferation data were negatively correlated with the concentration and percentage of butyric acid and positively correlated with the percentage of acetic acid, the acetic acid:butyric acid ratio and cecal pH. These results suggest that low rectal proliferation in animals fed a high fat, high starch diet might be associated with a lower relative concentration of butyric acid in the cecal contents.     

Fractionation and structural features of two heparin families with high antithrombotic, antilipemic and anticoagulant activities

15 heparin preparations from bovine intestine, pancreas and lung and hog intestine were fractionated in two main components by selective barium precipitation. The ones that precipitated at room temperature with barium (slow moving (SM)-heparins) had a high anticoagulant activity measured by the USP and APTT (activated partial thromboplastin time) assay and low antithrombotic activity by the Yin and Wessler method. The fractions precipitated at 5 degrees C with barium (fast moving (FM)-heparins) had a low anticoagulant action and high antithrombotic activity. The maximum anti-Xa activity (chromogenic method) was present in heparins with molecular weights around 12-15 X 10(3) daltons whereas high APTT and LPL releasing activities were present in SM-heparins with molecular weights of 30-40 X 10(3) and 15-25 X 10(3) daltons, respectively. FM-heparins had a higher anti-Xa activity and lower lipoprotein lipase (LPL)-releasing activity when compared with the SM-heparins with the same molecular weights. Significant structural differences were observed between SM- and FM-heparins by 13C-NMR spectra and enzymatic degradation with heparinase and heparitinase from Flavobacterium heparinum. Also, significant differences were observed for anti-Xa and anticoagulant activities for the two types of heparins depending on the pharmacological assay used.     

Combined metallothioneins and p53 proteins expression as a prognostic marker in patients with Dukes stage B and C colorectal cancer

Our study aimed to evaluate metallothionein and p53 expression in colorectal cancer and to correlate their combined expression with selected clinical and pathologic variables of the disease, to define their prognostic significance. Colorectal cancer specimens from 99 patients were retrospectively analyzed by immunohistochemistry for metallothionein and p53 expression. Survival curves were generated according to the Kaplan-Meier method, and univariate survival distributions were compared with the use of the log-rank test. Multivariate models were computed using Cox proportional hazards regression. This research was approved by the institutional review boards of all centers. Tumors showing concomitant high metallothionein expression and negative p53 (metallothionein(H)/p53(-)) were significantly inversely related to depth of invasion, frequency of nodal metastasis, and Dukes stage (P < .01). In univariate analysis, patients with metallothionein(H)/p53(-) phenotype showed a better overall survival (hazard ratio [HR], 2.83; P < .05) and disease-free survival (HR, 2.03; P < .05). In multivariate analysis, considering staging, metallothionein, and metallothionein + p53 variables, in 83 patients with Dukes stages B and C, metallothionein(H)/p53(-) combination was the sole factor showing an independent prognostic value for overall survival (HR, 3.88; P < .1) and disease-free survival (HR, 2.56; P < .1). In conclusion, the combined analysis of metallothionein and p53 may enhance the prognostic power of each individual marker by predicting the progression of the disease and contributing to a better identification of patients at low risk for mortality, especially for those with Dukes stage B and C colorectal cancer.     

Physiological effects of copper in the euryhaline copepod Acartia tonsa: waterborne versus waterborne plus dietborne exposure

The physiological effects of waterborne and waterborne plus dietborne copper exposure were determined in the euryhaline copepod Acartia tonsa at different salinities (5, 15 and 30ppt). Copepods were exposed (48h) to a reported 48-h LC50 for copper (CuCl(2)), which had been previously determined under the same experimental conditions. Whole body copper accumulation, ion concentrations (Na(+), Cl(-), Mg(2+)), and Na(+), K(+)-ATPase activity were the endpoints measured in all experimental groups. Feeding rate was also measured in fed experimental groups. In copper-exposed copepods, whole body copper accumulation was dependent on salinity, decreasing as salinity increased. However, it was similar in copepods exposed to waterborne and waterborne plus dietborne copper, irrespective the salinity tested. Waterborne copper exposure induced a disturbance of the whole body Na(+) concentration in all salinities tested. This effect was characterized by an increased whole body Na(+) concentration in seawater (salinity 30ppt) and a decreased whole body Na(+) concentration at lower salinities (5 and 15ppt). The ionoregulatory imbalance in low salinity (5ppt) was associated with an inhibition of the whole body Na(+), K(+)-ATPase activity, as observed in freshwater fish and crustaceans. When copepods were exposed to waterborne plus dietborne copper, the physiological effects described were only observed at a low salinity (5ppt) and were associated with a marked inhibition of the feeding rate. Taken altogether, the data suggest that the physiological effects induced by waterborne copper exposure in A. tonsa acclimated to higher salinities (15 and 30ppt) are due to a combined effect of food restriction and copper exposure. Differential physiological responses to waterborne and waterborne plus dietborne copper cannot be ascribed to differences in whole body copper burden.     

Randomized controlled trial: effects of diet on DNA damage in heavy smokers

We have conducted a randomized trial which investigated the ability of dietary changes (in particular diets rich in cruciferous vegetables and flavonoids), to increase urinary antimutagenicity and inhibit DNA damage in smokers. Ninety heavy smokers were recruited and randomly assigned to three groups, and were given three different diets. The first diet was based on flavonoid-rich foods, particularly cruciferous vegetables, but not based on supplementation; the second was a normal isocaloric diet (with an adequate administration of fruits and vegetables); and the third was based on supplementation of flavonoids in the form of green tea and soy products. DNA adducts were measured by (32)P-postlabelling in exfoliated bladder cells at different times since the start of the trial. In spite of randomization, subjects in the control group smoked more than those in the experimental groups, and this can explain the higher adduct levels at baseline. A slight decrease in bulky DNA adducts in exfoliated bladder cells was observed after 1 year since the end in the supplementation group and after 1 month in white blood cells. The only statistically significant association was found in a regression model that adjusted for smoking, in which the increase in flavonoid intake was associated with a decrease in adducts after 1 year (P = 0.02). These data suggest that adherence to a diet rich in cruciferous vegetables and flavonoids might reduce genotoxicity in the human urinary bladder of smokers, but they should be interpreted with caution owing to small numbers and the uneven distribution of smoking habits in the experimental groups. Smoking is the most important single preventable cause of cancer; at the present stage of knowledge it is totally unlikely that certain dietary habits can seriously counteract the effects of tobacco smoking.     

Clinical and socioeconomic impact of pediatric seasonal and pandemic influenza

Influenza is frequent among otherwise healthy day-care and school-aged children. Recent studies have demonstrated its significant effect on various outcome factors, including significantly more school and parental work absenteeism, and secondary illnesses among family members. Other studies have shown that the potential benefit of vaccinating children against influenza extends to other members of their families, thus supporting earlier economic modeling analyses of immunization programs. Although there are some differences in the clinical and socio-economic impact of seasonal and pandemic influenza, the benefits of vaccination are similar in both cases. The vaccination of otherwise healthy children may significantly reduce direct and indirect influenza-related costs, which supports the recommendation to make wider use of influenza vaccine in healthy children of any age in order to reduce the burden of infection on the community.     

Effect of copper on ion content in isolated mantle cells of the marine clam Mesodesma mactroides

The effect of copper on ion content (Na(+), K(+), Ca(2+), and Cl(-)) was evaluated in isolated mantle gills of the marine clam Mesodesma mactroides. Clams were collected at the Mar Grosso Beach (S?o José do Norte, Rio Grande do Sul [RS], southern Brazil), cryoanesthetized, and had their mantles dissected. Mantle cells were isolated and incubated in a calcium-free phosphate solution without (control) or with Cu (CuCl(2)). Cells were exposed to Cu for 1 h (5 μM) or 3 h (2.5 and 5 μM). In cells incubated with 2.5 μM Cu, a significant decrease in intracellular Cl(-) content was observed. However, in cells incubated with 5.0 μM Cu, significant reductions in Na(+), K(+), and Cl(-) intracellular content were observed. Given the mechanisms involved in ion transport in mantle cells of the marine clam M. mactroides, the findings described here suggest that Cu exposure inhibits carbonic anhydrase and Na(+)/K(+) -ATPase activity. Also, it can be suggested that Cu is competing with Na(+) for the same mechanisms of ion transport in the cell membrane, such as the Na(+) channels and the Na(+)/K(+)/2Cl(-) cotransporter. Results from the present study also clearly indicate that processes involved in cellular anion regulation are more sensitive to Cu exposure than those associated with the cellular cation regulation. Characterization of sites for Cu accumulation and toxicity in aquatic animals is important for derivation of metal binding constants at the biotic ligand. Also, identification of the mechanism of metal toxicity is needed for modeling metal accumulation in the biotic ligand and its consequent toxicity. Therefore, the findings reported here are extremely valuable for the development of a biotic ligand model version for marine and estuarine waters.     

Grey-Scale Analysis Improves the Ultrasonographic Evaluation of Thyroid Nodules

Ultrasonography is the main imaging method for the workup of thyroid nodules. However, interobserver agreement reported for echogenicity and echotexture is quite low. The aim of this study was to perform quantitative measurements of the degree of echogenicity and heterogeneity of thyroid nodules, to develop an objective and reproducible method to stratify these features to predict malignancy.A retrospective study of patients undergoing ultrasonography-guided fine-needle aspiration was performed in an University hospital thyroid center. From January 2010 to October 2012, 839 consecutive patients (908 nodules) underwent US-guided fine-needle aspiration. In a single ultrasound image, 3 regions of interest (ROIs) were drawn: the first including the nodule; the second including a portion of the adjacent thyroid parenchyma; the third, the strap muscle. Histogram analysis was performed, expressing the median, mean, and SD of the gray levels of the pixels comprising each region. Echogenicity was expressed as a ratio: the nodule/parenchyma, the nodule/muscle, and parenchyma/muscle median gray ratios were calculated. The heterogeneity index (HI) was calculated as the coefficient of variation of gray histogram for each of the 3 ROIs. Cytology and histology reports were recorded.Nodule/parenchyma median gray ratio was significantly lower (more hypoechoic) in nodules found to be malignant (0.45 vs 0.61; P = 0.002) and can be used as a continuous measure of hypoechogenicity (odds ratio [OR] 0.12; 95% confidence interval [CI] 0.03–0.49). Using a cutoff derived from ROC curve analysis (<0.46), it showed a substantial inter-rater agreement (k = 0.74), sensitivity of 56.7% (95% CI 37.4–74.5%), specificity of 72.0% (67.8–75.9%), positive likelihood ratio (LR) of 2.023 (1.434–2.852), and negative LR of 0.602 (0.398–0.910) in predicting malignancy (diagnostic odds ratio 3.36; 1.59–7.10). Parenchymal HI was associated with anti-thyroperoxidase positivity (OR 19.69; 3.69–105.23). The nodule HI was significantly higher in malignant nodules (0.73 vs 0.63; P = 0.03) and, if above the 0.60 cutoff, showed sensitivity of 76.7% (57.7–90.1%), specificity of 46.8% (42.3–51.4%), positive LR of 1.442 (1.164–1.786), and negative LR of 0.498 (0.259–0.960).Evaluation of nodule echogenicity and echotexture according to a numerical estimate (nodule/parenchyma median gray ratio and nodule HI) allows for an objective stratification of nodule echogenicity and internal structure.