Frequency of molecular alterations in heterozygous beta-thalassemia in southern Spain and their relation to the hematologic phenotype

INTRODUCTION: Heterozygous beta-thalassemia manifests hematologically with microcytosis, reduced red blood cell hemoglobin concentration and high hemoglobin A2 levels. Almost all molecular alterations are due to point mutations. We attempt to determinate the frequency of that mutations in the Oriental Andalusia Area, and its relationship with the hematological phenotype. PATIENTS AND METHODS: We have studied 45 heterozygous patients. DNA samples were amplified by PCR, using the printers CD7 and HI1. A 16 Kb fragment corresponding to beta globin gene was obtained and analyzed by Dot Blot assay and hybridized with allelic specific oligonucleotide (ASO) probes to detect the 6 more frequent mutations found in the South of Spain. RESULTS: Codon 39 nonsense mutation (31.1%) was the most frequent finding followed by IVS-1 NT 110 (26.7%). The relationship between hematological parameters and molecular mutations concluded that IVS-I NT 6 mutation developed a minimal anemia. DISCUSSION: From the practical point of view, this study indicates that we were able to detect more than 90% of heterozygous beta-tal. with 5 out of 6 ASO probes used in this work. Thus, our data also provides a further implication in prenatal diagnosis.     

Low birth weight as an additional indication for chromosomal analysis

INTRODUCTION: Even though there are few epidemiological studies evaluating the birth weights of different groups of malformed babies with chromosomal abnormalities, it is widely known that infants with trisomy 18, and to a lesser degree those with trisomy 13 and other chromosomal alterations, have low birth weights. PATIENTS AND METHODS: In this study we present the analysis of the birth weights and gestational ages of a large sample of babies (23,155 malformed and a similar number of nonmalformed babies), separating the different groups of chromosomal anomalies and comparing the weight in the clinical groups of malformed infants. RESULTS: Most of the groups with chromosomal abnormalities present lower birth weights in comparison to the other groups. CONCLUSIONS: The results of our study support the conclusion that the relationship between chromosomal alterations and low birth weight is sufficiently important that such a low birth weight in children with minor or major anomalies should be considered as one more indication to perform chromosomal analysis.     

Absence of detectable human herpesvirus 8 in the semen of human immunodeficiency virus-infected men without Kaposi's sarcoma

The prevalence of human herpesvirus 8 (HHV-8)/Kaposi's sarcoma (KS)-associated herpesvirus was investigated in the semen of 99 human immunodeficiency virus (HIV)-infected men (median CD4 cell count, 357/mm3) by use of a polymerase chain reaction (PCR) assay capable of detecting <10 copies of HHV-8 DNA. Of the subjects, 95 (96%) self-identified as men who have sex with men (MSM), and 3 had a history of clinical KS. Seminal cell specimens were negative for HHV-8 in 98 subjects. None of the 26 without KS (27.1% of 96 tested) who were seropositive for HHV-8 by IFA for latency-associated nuclear antigens had HHV-8 detected in their semen. The only subject with any evidence for seminal HHV-8 DNA was seropositive for HHV-8 and had active KS. HHV-8 was detected in 10 (10.4%) of 96 peripheral blood mononuclear cell specimens. The prevalence of HHV-8 DNA by PCR in semen of HIV-infected MSM without KS is low.     

Health research in the developing world: a gastroenterological view from Bangladesh

OBJECTIVES: To identify knowledge levels of academic surgeons about Food and Drug Administration (FDA) and Institutional Review Board (IRB) regulations for clinical research and to determine whether being a member in an IRB, conducting or participating in clinical trials, or being a member in surgical societies affected knowledge levels. DESIGN: Survey of surgical department faculty members in 20 universities. RESULTS: Sixty-five responses were received from 14 sites. Overall mean (+/- SEM) correct score was 6.7 +/- 0.2 of a possible 20 points. The best predictor of overall score was being a primary investigator of a clinical trial (P < .001), followed by being or having been a member of an IRB (P < or = .02). The total mean score of members of the Surgical Infection Society (8.2 +/- 0.5) was significantly higher (P < .001) than that of nonmembers (6.1 +/- 0.2), a phenomenon not observed with other surgical societies. In certain hypothetical clinical scenarios, all respondents were mistakenly willing to conduct clinical trials without obtaining appropriate approval from the FDA. Four (22%) of 18 IRB member respondents and 16 (25%) of the 65 respondents were willing to conduct human research without appropriate approval from patients, the IRB, or both. CONCLUSIONS: Knowledge deficits exist in the academic surgical community about the role and requirements of the FDA and local IRBs for conducting clinical research. Further study is required to determine the reasons for this deficit and to identify appropriate interventions.     

Cloning and disruption of the antigenic catalase gene of Aspergillus fumigatus

Aspergillus fumigatus possesses two catalases (described as fast and slow on the basis of their electrophoretic mobility). The slow catalase has been recognized as a diagnostic antigen for aspergillosis in immunocompetent patients. The antigenic catalase has been purified. The enzyme is a tetrameric protein composed of 90-kDa subunits. The corresponding cat1 gene was cloned, and sequencing data show that the cat1 gene codes for a 728-amino-acid polypeptide. A recombinant protein expressed in Pichia pastoris is enzymatically active and has biochemical and antigenic properties that are similar to those of the wild-type catalase. Molecular experiments reveal that CAT1 contains a signal peptide and a propeptide of 15 and 12 amino acid residues, respectively. cat1-disrupted mutants that were unable to produce the slow catalase were as sensitive to H2O2 and polymorphonuclear cells as the wild-type strain. In addition, there was no difference in pathogenicity between the cat1 mutant and its parental cat1+ strain in a murine model of aspergillosis.     

Prevalence of multiple cardiovascular disease risk factors among women in the United States, 1992 and 1995: the Behavioral Risk Factor Surveillance System

We sought to examine the prevalence of self-reported multiple cardiovascular disease (CVD) risk factors (hypertension, high blood cholesterol, diabetes, overweight, and current smoking) among women in 1992 and 1995 in the United States using data from the Behavioral Risk Factor Surveillance System. In 1992, 37.5%, 34.4%, and 28.1% of women had zero, one, and two or more of the five risk factors, respectively. In 1995, the respective estimates were 35.5%, 34.3%, and 30%. In both years, the prevalence of two or more risk factors increased with age, decreased with educational level, was higher among black women (lowest among Hispanic women and women of other ethnic groups), and higher among women reporting cost as a barrier to healthcare. The percentage of women with two or more risk factors was higher in 1995 than in 1992 for 35 of 48 states, being statistically significant for 7 states. The percentage of women with at least two risk factors was not significantly lower in 1995 than in 1992 for any state. A higher percentage of women reported having multiple CVD risk factors in 1995 compared with 1992. A multifactorial approach to primary prevention and risk factor reduction should be encouraged to help reduce the prevalence and burden of CVD among women.