Two new mutations and three novel polymorphisms in the<Emphasis Type="Italic"> RB1</Emphasis> gene in Ecuadorian patients

RB1 is the gene responsible for retinoblastoma, the most common malignant intraocular tumor of infancy and early childhood. There are no reports about this gene in Ecuadorian populations, and only a few studies have been published in Latin America about this subject. There is a spectrum of more than 370 mutations described in the RB1 gene mutation database (http://www.d-lohmann.de/Rb/mutations.html), and alterations have been found in 25 of the 27 exons. During the exon-by-exon analysis of 31 tumor and blood samples from Ecuadorian patients, we found two new mutations and three novel polymorphisms. One of the polymorphisms is located in intron 26 where no alterations of the gene have been described previously. The polymorphisms were found in all of the patients tumor samples, but not in normal population, suggesting there might be a relationship between these polymorphisms and the development of retinoblastoma in the Ecuadorian population.The nucleotide sequence data reported are available in the GenBank database under the accession numbers: AY243567, AY260472, AY260473, AY273783     

Expression of the proteoglycans versican and mel-CSPG in dysplastic nevi

Nevi with architectural disorder and cytologic atypia of melanocytes (NAD) (also called dysplastic nevi) have been controversial with regard to their relationship with melanoma risk and to their gradation in 3 degrees of atypia. Versican and the melanoma-associated proteoglycan (mel-CSPG) are 2 major proteoglycans expressed by malignant melanoma, and they have a role in the regulation of cell adhesion, migration, and differentiation. We evaluated the differences in versican and mel-CSPG expression in nevi, NAD with several degrees of atypia, and primary malignant melanoma. Immunoreactivity for versican was negative in benign melanocytic nevi, positive in NAD (ranging from weakly to intensely positive), and intensely positive in malignant melanoma. Immunostaining for mel-CSPG was negative in benign melanocytic nevi and mild to moderately positive in NAD and melanoma. Our results suggest that versican expression may be of value for distinguishing NAD from benign melanocytic nevi and for distinguishing severe NAD from mild and moderate NAD.     

Identification of 26 new constitutional RB1 gene mutations in Spanish, Colombian, and Cuban retinoblastoma patients

Constitutional mutations in the RB1 gene predispose to retinoblastoma development. Hence genetic screening of retinoblastoma patients and relatives is important for genetic counseling purposes. In addition, RB1 gene mutation studies may help decipher the molecular mechanisms leading to tumors with different degrees of penetrance or expressivity. In the course of genetically screening of 107 hereditary and non-hereditary retinoblastoma patients (11 familiar bilateral, 4 familiar unilateral, 49 sporadic bilateral and 43 sporadic unilateral) and kindred from Spain, Colombia and Cuba, using direct PCR sequencing, we observed 45 distinct mutations and four RB1 deletions in 53 patients (9 familiar bilateral, 2 familiar unilateral, 31 sporadic bilateral and 11 sporadic unilateral). Most of these mutations (26/45, 57%) have not been reported before. In 32 patients, the predisposing mutations correspond to nonsense (mainly CpG transitions) and small insertions or deletions whose expected outcome is a truncated Rb protein that lacks the functional pockets and tail. Five single aminoacid replacements and seventeen mutations affecting splicing sites were also observed in retinoblastoma patients. Two of these sixteen mutations are of unclear pathogenic nature.     

Alterations in iron metabolism in chronic anti-HCV positive hepatitis. The relationship with response to interferon treatment

A prospective study in which the existence of iron metabolism alterations (increase in the serum levels of iron and ferritin and the presence of iron in liver tissue) in a group of 53 patients diagnosed with chronic anti-HCV positive hepatitis was performed. The aim of the study was to determine whether these parameters influence the response to interferon treatment. Elevations were observed in the serum levels of iron and/or ferritin in 17 (32%) of the patients. Higher than normal values of serum iron or ferritin in pretreatment analyses were associated with worse therapeutic response. The basal serum levels of iron and ferritin were significantly higher in non responding patients. No relationship was found between the presence of iron in the hepatic parenchyma and response to interferon treatment.     

Minimum basic set of data of hospital discharges as a source of information for a study of congenital abnormalities

BACKGROUND: The purpose of this study is that of assessing the validity of the computerized diagnoses of hospital discharges of congenital defects by comparing them with the information included in the medical history. METHODS: Based on the discharge records generated over a one-year period at 7 hospitals in the Autonomous Region of Valencia, 100 children were selected at random from each hospital. As a standard, the diagnoses stated in the medical histories were indexed and coded. Solely those discharges having taken place during the first year of life were considered. A study was also made of the type, seriousness and individual or combinations of congenital defects. A calculation was made of the sensitivity, specificity, predictive values and the 95% confidence intervals thereof by the exact binomial method for the case studies (children) and the positive predictive value and sensitivity for the study of diagnoses. RESULTS: 126 children were detected as having congenital defects, and 201 diagnoses in medical records, and 83 children with congenital defects and 108 diagnoses on record. For the detection of cases, the records showed a 64% sensitivity, a 99.1% specificity and some positive and negative predictive values of over 90%. With regard to the detection of diagnoses, the sensitivity was 46% and the positive predictive value 83%. The sensitivity varied a great deal depending upon the diagnoses. CONCLUSIONS: The hospital discharge records revealed a high degree of specificity and high predictive values, but a low degree of sensitivity. These facts must be considered when these records are used as a source of cases for the epidemiological studies of congenital defects.     

Neutron activation analysis determination of body composition

The nutritional status of patients can be evaluated by monitoring changes in body composition, including the depletion of protein and muscle, adipose tissue distribution and changes in hydration status, bone or cell mass. Neutron activation analysis is a unique reference tool for the in-vivo determination of body composition. In this review we describe the recent changes in the field that followed the advent of new portable generators of fast neutrons, capable of performing elemental analysis in the clinical environment. New models were developed based on the partition of the measurable elements of the body. The recent developments help evaluate new treatments for wasting and obesity, in which change in body composition is the main outcome.     

Responsiveness of the hypothalamo-pituitary-interrenal axis in an amphibian (Bufo terrestris) exposed to coal combustion wastes

To assess the responsiveness of the interrenal axis to stress, we injected toads exposed to coal combustion wastes and toads from an unpolluted reference site with adrenocorticotropic hormone (ACTH), as well as the vehicle alone (saline). Initial circulating levels of corticosterone in toads captured at the polluted area were significantly higher than levels in toads from the reference site. Corticosterone levels in toads from the polluted site remained high even after 2 weeks of laboratory acclimation and injection with saline. The results may suggest disruption of hepatic enzymes responsible for the metabolic clearance of steroid hormones. Injection of toads from the polluted site with ACTH had no effect on plasma corticosterone levels, whereas a similar treatment of toads from the reference site stimulated a marked increase in corticosterone. Our study provides evidence that toads exposed to coal combustion wastes may be less efficient at responding to additional environmental stressors.