Chagas disease: an impediment in achieving the Millennium Development Goals in Latin America

Background  

Achieving sustainable economic and social growth through advances in health is crucial in Latin America within the framework of the United Nations Millennium Development Goals.     

Stem Cell Plasticity and Tissue Bioengineering: Great Expectations and Some Concerns

"Stem cells" are by definition cells that self-renew and that have the capacity to differentiate into several lineages. A recent series of studies has challenged fundamental concepts of stem cell biology by suggesting that the functional potential of stem cells is not restricted to the tissue source from which they are derived. The ability for cells of one tissue to produce cells of other developmentally unrelated tissues has been defined as cellular plasticity. Therefore, the utility of stem cell plasticity in cell replacement therapy should be unlimited. Multipotent stem cells may be used to develop replacement tissues for congenital or degenerative disorders, either on their own or in combination with other therapeutic approaches such us gene therapy. There are, however, several concerns regarding the concept of stem cell plasticity and the methods used to evaluate the starting population. (c) 2002 Prous Science. All rights reserved.     

Time estimation and performance on reproduction tasks in subtypes of children with attention deficit hyperactivity disorder.

This study compared Hispanic children (ages 7 to 11) with combined type (CT, n=33) and inattentive type (IT, n=21) attention deficit hyperactivity disorder (ADHD) and a control group (n=25) on time-estimation and time-reproduction tasks. The ADHD groups showed larger errors in time reproduction but not in time estimation than the control group, and the groups did not differ from each other on their performance on this task. Individual differences could not be accounted for by oppositional-defiance ratings and low math or reading scores. Although various measures of executive functioning did not make significant unique contributions to time estimation performance, those of interference control and nonverbal working memory did so to the time-reproduction task. Findings suggest that ADHD is associated with a specific impairment in the capacity to reproduce rather than estimate time durations and that this may be related to the children's deficits in inhibition and working memory.     

Frequency of mutations in rpoB and codons 315 and 463 of katG in rifampin- and/or isoniazid-resistant Mycobacterium tuberculosis isolates from northeast Mexico

A total of 48 isoniazid (INH)- and rifampin (RIF)-resistant Mycobacterium tuberculosis isolates, 19 INH-resistant isolates, and 9 RIF-resistant isolates were randomly selected and tested for detecting mutations at codons 315 and 463 of katG by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), and/or for detecting mutations at a 69-bp region of the rpoB gene by the INNO-LiPA Rif TB assay. Of the 67 INH-resistant isolates tested, 36 (53.7%) showed the mutation at codon 315 of katG; however, none of them showed the mutation at codon 463. The majority of the RIF-resistant samples analyzed (49 of 57, 86.0%) reacted positive with one of the four R-type probes. The R5-pattern (S531L mutation) was the most frequently observed (31 of 57, 54.4%), followed by R4a-pattern (H526Y mutation) 13 isolates (22.8%), R4b-pattern (H526D mutation) 4 isolates (7.0%), and R2-pattern (D516V mutation) 1 isolate (1.8%). Overall, there was agreement between the line probe kit and phenotypic RIF-susceptibility test for 56 (98.2%) of 57 RIF-resistant isolates tested. These results show that the mutation analysis at codon 315 of katG could be used as a screening assay prior to standard susceptibility testing, whereas mutations in the rpoB gene could be used successfully as genetic markers to rapidly detect RIF-resistant M. tuberculosis clinical isolates from northeast Mexico.     

Complex malformations of the female genital tract. New types and revision of classification

BACKGROUND: Complex malformations of the female genital tract are often incorrectly identified, treated and reported, probably due to not considering the malformation as a cause of the clinical symptoms and neither the embryological origin of the different elements of the genitourinary tract. METHODS: Complex malformations are studied and classified, and new types are presented. The new types of complex malformations presented are: (i) Cases of unilateral vaginal or cervico-vaginal atresia with renal agenesis and uterine duplication, with or without communication between hemiuteri; (ii) the unilateral Rokitansky syndrome; and (iii) the combination in the same patient of unilateral Rokitansky syndrome (Müllerian defect) on one side and blind vagina and ipsilateral renal agenesis syndrome (Wolffian defect) on the other side. RESULTS: A revised version of the clinical and embryological classification of genital malformations is presented and an associated diagram points out the origin of these malformations. CONCLUSIONS: These genital malformative anomalies reaffirm our hypothesis about the embryology of the human vagina as deriving from the Wolffian ducts and the Müllerian tubercle; and they show that gynecologists should be aware of the related symptoms and the embryology of the female genital tract in order to achieve a better comprehension of the malformations for their right correction or therapeutic approach.     

Efficacy and safety of peg-IFN alfa-2a with ribavirin for the treatment of HCV/HIV coinfected patients who failed previous IFN based therapy.

BACKGROUND: Interferon (IFN) regimens for HCV treatment are less effective in HCV/HIV-coinfected patients. There are no effective treatments for patients who fail IFN therapies. We examined the safety and efficacy of peginterferon alfa-2a (peg-IFNalpha-2a) plus ribavirin (RBV) in 41HCV/HIV-coinfected patients non-responsive to prior IFN treatment. METHODS: Patients received peg-IFNalpha-2a (180mg/week) plus RBV (800mg/day) for 24 weeks (n=41). At week 24, patients with non-detectable HCV RNA or > or =2-log decrease from baseline, received peg-IFNalpha-2a (180mg/week) plus RBV (800mg/day) for 24 weeks further. Patients not responding to treatment at week 24 were discontinued. RESULTS: Intent to treat (ITT) sustained viral response (SVR) was 21.9%. Patients who received at least 24 weeks of peg-IFNalpha-2a plus RBV treatment (n=35), SVR rates were 25.7%. SVR was associated with significant improvements in liver histology grade (p=0.02), stage (p=0.02), and fibrosis progression rate (FPR) (p=0.03). Patients that failed to achieve SVR had statistically significant decreases in grade (p=0.09) and FPR (p=0.01). CONCLUSION: peg-IFNalpha-2a plus RBV is effective and safe to achieve SVR in HCV/HIV coinfected patients non-responsive to prior IFN treatment. Patients that achieve SVR have significant improvements in liver histology parameters. In patients that do not achieve SVR there are histological benefits beyond virological response that suggest that peg-IFNalpha-2a+RBV therapy may decrease risk of progression to end stage liver disease.     

R1626 plus peginterferon Alfa-2a provides potent suppression of hepatitis C virus RNA and significant antiviral synergy in combination with ribavirin

R1626, a prodrug of the hepatitis C virus (HCV) RNA polymerase inhibitor R1479, showed time-dependent and dose-dependent reduction of HCV RNA levels in a previous study. The present study evaluated the efficacy and safety of R1626 administered for 4 weeks in combination with peginterferon alfa-2a +/- ribavirin in HCV genotype 1-infected treatment-naive patients. Patients were randomized to: DUAL 1500 (1500 mg R1626 twice daily [bid] + peginterferon alfa-2a; n = 21); DUAL 3000 (3000 mg R1626 bid + peginterferon alfa-2a; n = 32); TRIPLE 1500 (1500 mg R1626 bid + peginterferon alfa-2a + ribavirin; n = 31); or standard of care (SOC) (peginterferon alfa-2a + ribavirin; n = 20). At 4 weeks HCV RNA was undetectable (<15 IU/mL) in 29%, 69%, and 74% of patients in the DUAL 1500, DUAL 3000, and TRIPLE 1500 arms, respectively, compared with 5% of patients receiving SOC, with respective mean reductions in HCV RNA from baseline to week 4 of 3.6, 4.5, 5.2, and 2.4 log(10) IU/mL. Synergy was observed between R1626 and peginterferon alfa-2a and between R1626 and ribavirin. There was no evidence of development of viral resistance. Adverse events (AEs) were mainly mild or moderate; seven patients had nine serious AEs (including one patient with one serious AE in SOC). The incidence of Grade 4 neutropenia was 48%, 78%, 39%, and 10% in DUAL 1500, DUAL 3000, TRIPLE 1500, and SOC, respectively, and was the main reason for dose reductions. Conclusion: A synergistic antiviral effect was observed when R1626 was combined with peginterferon alfa-2a +/- ribavirin; up to 74% of patients had undetectable HCV RNA at week 4. Dosing of R1626 was limited by neutropenia; a study of different dosages of R1626 in combination with peginterferon alfa-2a and ribavirin is underway.     

Thyroid dysfunction (TD) among chronic hepatitis C patients with mild and severe hepatic fibrosis

Background: Thyroid dysfunction (TD) is associated to chronic hepatitis C (HCV) and interferon (IFN) therapy. The prevalence of TD at baseline and during IFN therapy among stages of hepatic fibrosis is unknown.Goals: To examine the frequency of TD at baseline and during Peg-IFN therapy among patients with severe and mild fibrosis.Study: 100 patients were treated with Peg-IFN and divided in 2 groups (50 each), according to liver histology; Metavir 0-2 (mild fibrosis) and Metavir 3-4 (severe fibrosis). Baseline TD was defined as history of TD, or abnormal thyroid stimulating hormone (TSH) or antiperoxidase thyroid auto-antibodies (TPO-Ab). Frequency of TD during therapy was defined as TD that required treatment.Results: 20% in the severe fibrosis group and 10% in the mild fibrosis group, had TD at baseline. Most of the cases, 31.4% were female as compared to 6.25% males. During therapy, 24% of patients in the severe fibrosis group, compared to 12% in the mild fibrosis, had TD. Most patients had biochemical hypothyroidism, and 66% were female, compared to 33.33 % male. TPO-Ab predicted TD during therapy in 50% of cases while those negative only had 16.6% TD during IFN therapy.Conclusions: Patients with severe fibrosis have more TD events at baseline and during treatment with Peg IFN alfa-2a. Patients with more hepatic fibrosis require careful attention to diagnose and manage TD. More research in the immune mechanisms of hepatic fibrosis progression and autoimmune complications is needed.