Management of chronic viral hepatitis in HIV-infected patients: Spanish Consensus Conference. October 2000

Co-infection by human immunodeficiency virus and hepatitis B and C viruses is quite common because they share similar routes of transmission. The introduction of highly active antiretroviral therapy has significantly improved the life expectancy of HIV-infected patients in the last few years. However, chronic viral hepatitis represents an emerging cause of morbidity and mortality in this population, either as a result of end-stage liver disease or as a consequence of hepatotoxicity induced by antiretroviral drugs. The main goal of the Consensus Conference was to establish specific recommendations for the management of chronic viral hepatitis B and C in HIV-infected patients. The role of orthotopic liver transplantation for co-infected individuals with end-stage liver disease was also assessed.     

Influences of hormone replacement therapy on postmenopausal women's health perceptions

OBJECTIVE: To assess the beliefs of climacteric women regarding their health, menopause, and hormone replacement therapy (HRT). DESIGN: Medical students asked to interview 526 healthy women, ranging from 40 to 64 years of age, between January and February of 2002. Of that number, 26 (4.9%) declined to participate in the interview. Thus, 500 women were interviewed about their beliefs and perceptions regarding their quality of life and health risks, as well as their opinions on menopause and HRT. RESULTS: The mean age of the sample was 53.3 +/- 6.2 years; 83.4% were postmenopausal, and 18.8% were HRT users. Of the women interviewed, 38.6% believed that their health was good. Although 78.8% thought that cancer is the main cause of death, 64% of them considered themselves to be at high risk for cardiovascular disease and osteoporosis. Most (64%) believed that menopause deteriorates the quality of life and that it increases cardiovascular risk (52.4%) and osteoporosis (72.0%). The HRT users perceived that they had better health status (48.9% v 36.2%, P < 0.02) and smaller cardiovascular risk (54.3% v 66.3%, P < 0.04) than did the nonusers; however, they ignored the preventive effect of estrogens in osteoporosis. CONCLUSIONS: Women believe that menopause deteriorates their health. The HRT users perceived themselves to be healthier and to have a smaller risk for cardiovascular disease.     

Specific allergens enhance elastase release in stimulated neutrophils from asthmatic patients

BACKGROUND: The presence of the three forms of IgE receptor - the heterotrimeric high-affinity receptor for IgE (Fc(epsilon)RI), the low-affinity receptor for IgE (Fc(epsilon)RII/CD23) and the Mac-2/IgE-binding protein (epsilonBP) - has been demonstrated on human neutrophils. We have previously shown that specific allergens are able to activate functional responses by neutrophils from allergic patients sensitized to those allergens. Neutrophils are present at the sites of allergic inflammation. The primary (azurophilic) granules of neutrophils contain a variety of enzymes, such as elastase, that might potentiate inflammation. It is not known whether specific allergens are able to elicit elastase release by neutrophils from allergic patients. In addition, we attempted to evaluate the relationship between neutrophil degranulation and lung function of the patients, measured as FEV(1). METHODS: Neutrophils were challenged in vitro with the specific allergens that produced clinical symptoms in asthmatic patients. The cells were also challenged with allergen to which the patients were not sensitive. Neutrophils from normal subjects were challenged with allergens as control. RESULTS: The in vitro challenge of neutrophils with allergens to which the patients were sensitive elicited a release of elastase by these cells. The in vitro activation of neutrophils was highly allergen specific; allergens other than those accounting for clinical symptoms did not evoke elastase release, and allergens were ineffective on neutrophils from healthy donors. A significant inverse correlation was observed between elastase release and patients' lung function, measured as FEV(1). CONCLUSION: An IgE-dependent mechanism might promote elastase release by neutrophils at allergic sites. There is a significant inverse relationship between levels of elastase released by neutrophils from allergic patients and lung function, as assessed by FEV(1).     

Dopamine receptors in human brain: autoradiographic distribution of D1 sites

The distribution of dopamine D1 receptors has been determined in post mortem human brain tissues using in vitro receptor autoradiography, with ([3H]N-methyl) SCH 23390 as ligand. The highest densities of dopamine D1 sites were seen in the nucleus caudatus, putamen, globus pallidus pars medialis and substantia nigra. Intermediate densities were associated with the amygdala, mammillary bodies, cerebral cortex and CA1. The remaining part of the hippocampus as well as the diencephalon, brainstem and cerebellum contained low levels of [3H]SCH 23390 binding sites. The distribution of D1 receptors in the human brain closely resembles that reported for the rat brain. In addition, there was a good correlation between the anatomical localization of D1 sites and the distribution of dopaminergic nerve terminals in the central nervous system. The densities of D1 receptors in the human brain were observed to markedly decrease with age during the first decades of life. However, no further modifications were found beyond the age of 40 years. We did not observe any significant influence of other parameters such as gender and post mortem delay in our samples.     

Quantitative light microscopic autoradiographic localization of cholinergic muscarinic receptors in the human brain: forebrain

The distribution of muscarinic cholinergic receptors in the human forebrain and cerebellum was studied in detail by quantitative autoradiography using N-[3H]methylscopolamine as a ligand. Only postmortem tissue from patients free of neurological diseases was used in this study. The highest densities of muscarinic cholinergic receptors were found in the striatum, olfactory tubercle and tuberal nuclei of the hypothalamus. Intermediate to high densities were observed in the amygdala, hippocampal formation and cerebral cortex. In the thalamus muscarinic cholinergic receptors were heterogeneously distributed, with densities ranging from very low to intermediate or high. N-[3H]Methylscopolamine binding was low in the hypothalamus, globus pallidus and basal forebrain nuclei, and very low in the cerebellum and white matter tracts. The localization of the putative muscarinic cholinergic receptors subtypes M1 and M2 was analysed in parallel using carbachol and pirenzepine at a single concentration to partially inhibit N-[3H]methylscopolamine binding. Mixed populations of both subtypes were found in all regions. M1 sites were largely predominant in the basal ganglia, amygdala and hippocampus, and constituted the majority of muscarinic cholinergic receptors in the cerebral cortex. M2 sites were preferentially localized in the diencephalon, basal forebrain and cerebellum. In some areas such as the striatum and substantia innominata there was a tendency to lower densities of muscarinic cholinergic receptors with increasing age. In general, we observed a slight decrease in M2 sites in elderly cases. Muscarinic cholinergic receptor concentrations seemed to be reduced following longer postmortem periods. The distribution of acetylcholinesterase was also studied using histochemical methods, and compared with the localization of muscarinic cholinergic receptors and other cholinergic markers. The correlation between the presence of muscarinic cholinergic receptors and the involvement of cholinergic mechanisms in the function of specific brain areas is discussed. Their implication in neurological diseases is also reviewed.     

Immunohistochemical classification of non-BRCA1/2 tumors identifies different groups that demonstrate the heterogeneity of BRCAX families.

Around 25% of hereditary breast and ovarian cancer families have mutations in the BRCA1 and BRCA2 genes. The search for other genes has until now failed, probably because there is not one single BRCAX gene, but rather various genes that may each be responsible for a small number of breast cancer families and/or may interact according to a polygenic model. We have studied 50 tumors from probands belonging to non-BRCA1/2 breast cancer families (BRCAX), using 25 immunohistochemical markers. The objective was to classify these tumors and confirm that they are heterogeneous. Unsupervised cluster analysis showed the existence of the following two main groups of tumors: high-grade and estrogen receptor (ER)-negative tumors (50%), and low-grade and ER-positive tumors (50%). In addition we identified five subgroups, three among the high-grade and two among the low-grade groups; one overexpressing HER-2 (18%); one with a basal-like phenotype (14%); one with a normal breast-like phenotype (18%); a luminal A subgroup (36%), and a luminal B subgroup (14%). Hypermethylation of the BRCA1 gene was observed in 42% of the cases, spread across all five subgroups, but only 37% of those had loss of heterozygosity as well. These latter cases were all clustered in the high-grade group and the majority of them in the basal-like subgroup. Our results show that familial non-BRCA1/2 tumors are heterogeneous and suggest a polygenic model for explaining the majority of BRCAX families. In addition we have defined a subset of them that have somatic inactivation of the BRCA1 gene.     

Multivariate Base Rates of Low Scores on Tests of Learning and Memory among Spanish-Speaking Children

ABSTRACT

To determine the prevalence of low scores on two neuropsychological tests commonly used to evaluate learning and memory in children. 6,030 healthy children from 10 countries in Latin America and Spain were administered Rey–Osterrieth Complex Figure (ROCF) and the Test de Aprendizaje y Memoria Verbal–Infantil (TAMV-I). Results showed that low scores are common when multiple neuropsychological outcomes (tests and/or scores) are evaluated in healthy individuals. Clinicians should consider the higher probability of low scores in a given individual when evaluating learning and memory using various sets of scores to reduce false-positive diagnoses of cognitive deficits in pediatric populations.     

Susceptibility to DNA damage induced by antibiotics in lymphocytes from malnourished children

Infectious disease and malnutrition in children are public health problems in developing countries. Malnutrition is associated with higher levels of DNA damage, and this increased damage could be due to different factors, including the possibility that cells from malnourished children could be more susceptible to environmental damage. The aim of the present study was to evaluate the susceptibility of lymphocytes from malnourished children to DNA damage induced by antibiotics by using the comet assay. The same group of malnourished infected children were studied before and after a treatment period, and compared to a group of well-nourished infected children. Results showed that before and after drug treatment, tail length migration was two times greater in malnourished than in well-nourished children. The proportion of cells with high damage was also increased in malnourished children. Additionally in well-nourished and malnourished children, a cell subpopulation (non-damaged cells) more resistant to DNA damage induced by antibiotics was observed; this was more prevalent in the well-nourished children. Meanwhile, in malnourished children, a cell population seems to be more susceptible and reaches higher levels of DNA damage. This might help explain the impaired immune response observed in malnourished children. The increased DNA migration and the increased proportion of cells with higher levels of damage seem to indicate that malnourished children are more susceptible to DNA damage induced by drugs.     

Paratesticular congenital malignant rhabdoid tumor diagnosed by fine-needle aspiration cytology. a case report

We report the FNA features of a congenital malignant extrarenal rhabdoid tumor (MERT) located in the right paratesticular area of a newborn full-term boy (39 wk gestation), with disseminated metastases in the liver and right parietal region. The diagnosis was suggested two days after birth by fine-needle aspiration biopsy (FNAB) of the parietal mass, which demonstrated an atypical large cell proliferation with vesicular nuclei, prominent nucleoli, and abundant cytoplasm exhibiting paranuclear dense inclusions. The diagnosis was confirmed by histopathologic and immunohistochemical examination of the primary paratesticular tumor. To the best of our knowledge, this is the third MERT reported in the paratesticular region, one of the few congenital extrarenal non-central nervous system cases, and the third congenital case (renal or extrarenal) primarily diagnosed by FNAB. We emphasize the characteristic cytologic features of a congenital rhabdoid tumor, which must be known by pathologists because of the clinical and prognostic implications. Diagn. Cytopathol. 2004;30:46-50.     

A chromosome No. 2 abnormality in a child with a few congenital defects*

An abnormal chromosome No. 2 was found in the case of a child with an imperforate anus, a recto-vaginal fistula, unilateral atresia of the inner canal, and deformity of the external ear. G-banding studies revealed an insertion of a segment of the short arm into the long arm in one of the chromosomes No. 2 of the proband, the apparent result of a de novo phenomenon of chromosome rearrangement.