AIDS incidence and mortality in a hospital-based cohort of HIV-1-seropositive patients receiving highly active antiretroviral therapy in São Paulo, Brazil

Brazilian AIDS and HIV-1-seropositive patients have had free access to highly active antiretroviral therapy (HAART) since November 1996. Although secondary data based on official mortality statistics indicate a sharp decrease in AIDS mortality, few if any studies tried to estimate the prognosis for patients with HIV who have been followed from the beginning of the HAART era. An observational study, with retrospective and prospective components, was done in 233 adult HIV-1-infected subjects who were recruited in the last 10 years at the outpatient sector of the Secondary Immunodeficiencies Clinic of the Department of Dermatology, Hospital das Clinicas da FMUSP, Sao Paulo, Brazil. The definition of AIDS followed the guidelines issued by the Centers for Disease Control (CDC) in 1987. One hundred sixty patients were asymptomatic, 46 had AIDS, 24 had AIDS-related complex, and 3 presented with acute infection at study entry. Twenty-nine (18%) of the asymptomatic subjects developed AIDS during follow-up, with 5 (3%) deaths. Among the 46 AIDS cases at entry, 7 (17%) died during follow-up. Thus, a total of 12 people (5.2%) died of AIDS in this cohort over a mean follow-up of 5.2 years and 24 people were lost to follow-up (10.3%). Ninety percent of the survivors were on combined therapy (82% with 3 or more drugs, and 8% with 2 drugs), while 10% were not taking antiretrovirals. People with AIDS at entry were 5 times more likely to die during this period compared to patients who were asymptomatic at entry (p = 0.006). Women showed better outcomes than men, reflecting differences in CD4+ T-cell counts at study entry. All but 1 patient progressed to AIDS during the pre-HAART era (before 1996). In spite of its recent decline, mortality from AIDS-related conditions remains an important public health issue.     

Three new structural variants of fetal hemoglobin: Hb F-Campinas [Agamma g121(GH4)Glu --> Gln], Hb F-Paulinia [Ggamma 80(EF4)Asp --> Tyr] and Hb F-Joanopolis [Ggamma73(E17) Asp -->Ala

Three new structural variants of fetal hemoglobin were detected in newborns during a neonatal screening for Hb S in the southeast of Brazil: Hb F-Campinas [AgammaI121 (GH4)Glu --> Gln], Hb F-Paulinia [Ggamma80(EF4)Asp -->Tyr] and Hb F-Joanopolis [Ggamma73(E17) Asp -->Ala]. These variants were not related to clinical abnormalities     

Gastric Emptying and Gastrointestinal Transit of Liquid in Awake Rats Is Delayed After Acute Myocardial Infarction

The outcome of acute myocardial infarction (AMI) on gastrointestinal motor behavior was assessed in awake rats. Under anesthesia, they were submitted to thoracotomy followed or not by occlusion of the left coronary artery. Next day, they were gavage fed (1.5 ml) with phenol red in 5% glucose solution and sacrificed 10, 20, or 30 min later. Each subset consisted of 7 to 19 animals. Dye recovery in the stomach, proximal, mid, and distal small intestine was obtained by spectrophotometry. Infarcted left ventricle plus septum area was about 48.9 +/- 2.8, 55.1 +/- 6.7, and 54.1 +/- 8.1% (respectively, for 10-, 20-, and 30-min subsets). AMI increased gastric dye retention by 25.5, 51.3, and 65.1% (respectively, for 10-, 20-, and 30-min subsets), while it decreased mid small intestine retention at 30 min (45.3%) as well as distal retention at 10 min (90.5%) and 20 min (90%). A positive correlation (rS = 0.64) was found between infarcted area and gastric retention values at 10 min. AMI also increased (P < 0.05) central venous pressure values in all subsets (3.8 +/- 0.2 vs. -2.1 +/- 1.5, 1.4 +/- 0.1 vs. 0.5 +/- 0.2, and 1.6 +/- 0.4 vs. -0.2 +/- 0.3 cm H2O), while it decreased (P < 0.05) mean arterial pressure (95.0 +/- 2.6 vs. 110.0 +/- 3.9 and 106.0 +/- 2.0 vs. 113.0 +/- 3.0 mm Hg, respectively, at 10 and 30 min), and increased (P < 0.05) the 10-min heart rate values (429.6 +/- 11.3 vs. 374.0 +/- 19.8 bpm). Omeprazole pretreatment did not alter this phenomenon. In another group of rats, cardiac chemoreflex stimulation by i.v. phenylbiguanide increased gastric dye retention by 51.1%. In conclusion, AMI delays the gastric emptying and gastrointestinal transit of liquid in awake rats.     

Effect of ultrasonic tip and root-end filling material on bond strength

Objectives

The objective of this study was to evaluate the bond strength of three root-end filling materials (MTAA–MTA Angelus, MTAS–experimental MTA Sealer, and ZOE- zinc oxide and eugenol cement) in retrograde preparations performed with different ultrasonic tips (CVD, Trinity, and Satelec).

Materials and method

Ninety 2-mm root sections from single-rooted human teeth were used. The retrograde cavities were prepared by using the ultrasonic tips, coupled to a device for position standardization. The specimens were randomly divided into nine groups: CVD MTAA; CVD MTAS; CVD ZOE; Trinity MTAA; Trinity MTAS; Trinity ZOE; Satelec MTAA; Satelec MTAS; Satelec ZOE. Each resin disc/dentin/root-end filling material was placed in the machine to perform the push-out test. The specimens were examined in a stereomicroscope to evaluate the type of failure. Data were submitted to statistical analysis using ANOVA and Tukey tests (α?=?0.05).

Results

The highest bond strength was observed for the CVD tip irrespective of the material used (P?<?0.05). There was no significant difference for the Trinity TU-18 diamond and S12 Satelec tips (P?>?0.05). MTAA and MTAS showed highest bond strength. The most common type of failure was adhesion between the filling material and dentin wall, except for ZOE, where mixed failure was predominant.

Conclusions

The CVD tip favored higher bond strength of the root-end filling materials. MTA Angelus and experimental MTAS presented bond strength to dentin prepared with ultrasonic tips.

Clinical relevance

Root-end preparation with the CVD tip positively influences the bond strength of root-end filling materials. MTA Angelus and experimental MTAS present bond strength to be used as root-end filling materials.

     

Genital mycoplasmas in women attending a family planning clinic in Guiné-Bissau and their susceptibility to antimicrobial agents

A study on the prevalence of genital mycoplasmas and their susceptibility to the most common antimicrobial agents used for treating the infection was conducted on 94 women attending a family planning clinic in Guiné-Bissau. Fifty-four women (57.4%) were positive for Mycoplasma hominis and/or Ureaplasma urealyticum. M. hominis and U. urealyticum separately isolated from infected women yielded frequencies of 31.5 and 27.8%, respectively, the remainder were infected with both species. No strain was found to be resistant to all three commonly employed antibiotics for the management of these infections (erythromycin, tetracycline and ofloxacin), although multiple resistance to two antibiotics was frequent, especially when both genital mycoplasmas were present. Some 90.7 and 24.1% of all isolates were resistant to erythromycin and tetracycline, respectively. No resistance was observed to ofloxacin, although 50% of the strains had intermediate resistance. The high prevalence of genital mycoplasmas in women attending a family planning clinic in Guiné-Bissau, as demonstrated in this study, appears to be associated with trichomonosis and bacterial vaginosis. These infections were also found to be highly resistant to erythromycin and tetracycline and to have intermediate resistance to ofloxacin. However, further studies are necessary to establish the burden of infection due to antibiotic resistant genital mycoplasmas.     

Wine polyphenols improve endothelial function in large vessels of female spontaneously hypertensive rats

Red wine polyphenols (RWPs) have been reported to prevent hypertension and endothelial dysfunction. Several individual RWPs exert estrogenic effects. We analyzed the possible in vivo protective effects on blood pressure and endothelial function of RWPs in female spontaneously hypertensive rats (SHR) and its relationship with ovarian function. RWPs (40 mg/kg by gavage) were orally administered for 5 weeks. Ovariectomized rats showed both increased isoprostaglandin F(2alpha) excretion and aortic superoxide production and reduced relaxant response to acetylcholine and contraction to the endothelial nitric oxide synthase (eNOS) inhibitor l-NAME measured in the aorta but similar blood pressure, as compared with sham-operated rats. Moreover, in ovariectomized rats aortic eNOS expression was unchanged, whereas caveolin-1, angiotensin II receptor (AT)-1, and the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits p22(phox) and p47(phox) expression was increased compared with sham-operated rats. In both ovariectomized and sham-operated SHR, RWPs reduced systolic blood pressure, urinary isoprostaglandin F(2alpha) excretion, and aortic O(2)(-) production, improving the endothelium-dependent relaxant response to acetylcholine in SHR. These changes were associated with unchanged aortic eNOS expression, whereas caveolin-1 was increased and the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits p22(phox) and p47(phox) expression was reduced. RWPs had no effect on the AT-1 overexpression found in ovariectomized animals. All these results suggest that a chronic treatment with RWPs reduces hypertension and vascular dysfunction through reduction in vascular oxidative stress in female SHR in a manner independent of the ovarian function.     

Rapid fitness losses in mammalian RNA virus clones due to Muller''s ratchet.

Muller's ratchet is an important concept in population genetics. It predicts that when mutation rates are high and a significant proportion of mutations are deleterious, a kind of irreversible ratchet mechanism will gradually decrease the mean fitness of small populations of asexual organisms. In contrast, sexual recombination may stop or reverse this mutational ratchet by recombinational repair of genetic damage. Experimental support for Muller's ratchet has previously been obtained in protozoa and in a tripartite RNA bacteriophage. We now show clear evidence that Muller's ratchet can operate on a nonsegmented nonrecombining pathogenic RNA virus of animals and humans. We did genetic bottleneck passages (plaque-to-plaque transfers) of vesicular somatitis virus (VSV) and then quantitated relative fitness of the bottleneck clones by allowing direct replication competition in mixed infections in cell culture. We document variable fitness drops (some severe) following only 20 plaque-to-plaque transfers of VSV. In some clones no fitness changes (or only insignificant changes) were observed. Surprisingly, the most regular and severe fitness losses occurred during virus passages on a new host cell type. These results again demonstrate the extreme genetic and biological variability of RNA virus populations. Muller's ratchet could have significant implications for variability of disease severity during virus outbreaks, since genetic bottlenecks must often occur during respiratory droplet transmissions and during spread of low-yield RNA viruses from one body site to another (as with human immunodeficiency virus). Likewise, the lower-probability generation of increased-fitness clones during repeated genetic bottleneck transfers of RNA viruses in nature might also affect disease pathogenesis in infected individuals and in host populations. Whenever genetic bottlenecks of RNA viruses occur, enhanced biological differences among viral subpopulations may result.     

Native valve endocarditis due to <Emphasis Type="Italic">Pichia ohmeri</Emphasis>

Candida species can cause clinical manifestations in various organs of the cardiovascular system, i.e., the pericardium, myocardium, and endocardium, with endocarditis being the best-known clinical entity. Endocarditis is seen primarily in intravenous drug users and in individuals with damaged native valves, especially in congenital heart disease or rheumatic valvular diseases, and in prosthetic heart valves. The authors present a case of Pichia ohmeri endocarditis in an intravenous drug user, with an unusual presentation form. This is a case of a 42-year-old man, an intravenous heroin user, who was admitted to our Vascular Surgery Department because of fever and acute serious ischemia of the left inferior limb. He presented with fever (39 degrees C), a pale and cold left limb, absence of the left popliteal pulse, and a pansystolic murmur at the cardiac apex. The transthoracic echocardiogram showed a large vegetation on the anterior leaflet of the mitral valve and severe mitral regurgitation with good left ventricular systolic function. Empirical antibiotic therapy was started. Six days after admission, embolectomy was performed with partial clinical recovery. Three blood cultures and the embolus showed a teleomorphic form of Candida guilliermondii - Pichia ohmeri. Therapy with intravenous liposomal amphotericin B, fluocitosin, imipenem, and aztreonam was started. Two weeks later, his clinical condition deteriorated with acute heart failure refractory to medical therapy, mandating mechanical ventilation and high-dose vasopressor and inotropic amine support. He underwent urgent mitral valve replacement with a biologic prosthetic valve. Rapid stabilization of the cardiac status occurred, but ischemic limb lesions required further vascular interventions.     

A survey of congenital Chagas' disease, carried out at three health institutions in São Paulo City, Brazil

The congenital transmission of Chagas' disease was evaluated in 57 pregnant women with Chagas' disease and their 58 offspring. The patients were selected from three Health Institutions in S?o Paulo City. The maternal clinical forms of Chagas' disease were: indeterminate (47.4%), cardiac (43.8%) and digestive (8.8%); 55 were born in endemic areas and two in S?o Paulo City. The transmission of Chagas' disease at fetal level was confirmed in three (5.17%) of the 58 cases studied and one probably case of congenital Chagas' disease. Two infected infants were born to chagasic women with HIV infection and were diagnosed by parasitological assays (microhematocrit, quantitative buffy coat-QBC or artificial xenodiagnosis). In both cases the placenta revealed T. cruzi and HIV p24 antigens detected by immunohistochemistry. In one case, a 14-week old abortus, the diagnosis of congenital T. cruzi infection was confirmed by immunohistochemistry. The other probable infection, a 30-week old stillborn, the parasites were found in the placenta and umbilical cord. The Western blot method using trypomastigote excreted/secreted antigens of T. cruzi (TESA) was positive for IgG antibodies in 54/55 newborns and for IgM in 1/55 newborns. One of the two newborns with circulating parasites had no detectable IgG or IgM antibodies. The assessment of IgG antibodies in the sera of pregnant women and their newborns was performed by ELISA using two different T. cruzi antigens: an alkaline extract of epimastigotes (EAE) and trypomastigote excreted/secreted antigens (TESA). The analysis showed a linear correlation between maternal and newborn IgG antibody titers at birth.