High frequency of skin reactions in patients with leishmaniasis treated with meglumine antimoniate contaminated with heavy metals: a comparative approach using historical controls

We analyzed data from historical controls treated with meglumine antimoniate to compare the frequency of adverse events observed in patients with cutaneous leishmaniasis treated with the same dose of meglumine antimoniate contaminated with heavy metals in an endemic area of the State of Bahia, Brazil. Group A patients were treated in 2000 with the drug produced by Eurofarma Laboratórios Ltda., São Paulo, Brazil (lot A) and group B patients were treated in 1996 with the reference drug produced by Rhodia Farma Ltda., São Paulo, Brazil (lot B). We observed an unusual higher frequency of skin reactions in group A patients. However, all type of adverse events observed in group A were also observed in group B. The physico-chemical analysis of these lots revealed that lot A had lower pH and higher concentration of total and trivalent antimony, lead, cadmium, and arsenic. Our findings suggest that the skin reactions could be attributed to heavy metal contamination of lot A.

Hepatitis B genotype G and high frequency of lamivudine-resistance mutations among human immunodeficiencyvirus/hepatitis B virus co-infected patients in Brazil

In this study, we evaluated the hepatitis B virus (HBV) genotype distribution and HBV genomic mutations among a group of human immunodeficiency virus-HBV co-infected patients from an AIDS outpatient clinic in São Paulo. HBV serological markers were detected by commercially available enzyme immunoassay kits. HBV DNA was detected using in-house nested polymerase chain reaction and quantified by Cobas Amplicor. HBV genotypes and mutations in the basal core promoter (BCP)/pre-core/core regions and surface/polymerase genes were determined by sequencing. Among the 59 patients included in this study, 55 reported prior use of lamivudine (LAM) or tenofovir. HBV DNA was detected in 16/22 patients, with a genotype distribution of A (n = 12,75%), G (n = 2,13%), D (n = 1,6%) and F (n = 1,6%). The sequence data of the two patients infected with genotype G strongly suggested co-infection with genotype A. In 10 patients with viremia, LAM-resistance mutations in the polymerase gene (rtL180M + rtM204V and rtV173L + rtL180M + rtM204V) were found, accompanied by changes in the envelope gene (sI195M, sW196L and sI195M/sE164D). Mutations in the BCP and pre-core regions were identified in four patients. In conclusion, genotype G, which is rarely seen in Brazil, was observed in the group of patients included in our study. A high prevalence of mutations associated with LAM-resistance and mutations associated with anti-HBs resistance were also found among these patients.

Molecular characterization of G and P-types bovine rotavirus strains from Goiás, Brazil: high frequency of mixed P-type infections

In this study, 331 samples from calves less than one month old from a dairy herd in the district of Piracanjuba, state of Goiás, Brazil were tested for rotavirus. Thirty-three samples (9.9%) tested positive for rotavirus. Out of those, 31 were submitted to G and P characterization by reverse transcription followed by semi-nested polymerase chain reaction. Two samples were characterized as G6P[1], three as G10P[11] and five as G6P[11]. The majority of the samples (51.6%) displayed multiple P genotypes (P-genotype mixtures), including typical human genotypes P[4] and P[6M], suggesting the occurrence of co-infections and genetic reassortment. Also, the detection of human genotypes in bovine samples may be considered evidence of the zoonotic potential of rotaviruses. To our knowledge, this is the first report of such a high frequency of P genotype mixtures in bovine rotavirus samples. It also increases data on G and P rotavirus genotypes circulating in dairy herds in Brazil and can help in the development of more efficient immunization approaches, thereby controlling infection and reducing economical losses.

Low occurrence of occult hepatitis B virus infection and high frequency of hepatitis C virus genotype 3 in hepatocellular carcinoma in Brazil

Occult hepatitis B virus (HBV) infection has been reported among patients with hepatitis C virus (HCV) infection and hepatocellular carcinoma (HCC). Our aim was to evaluate the presence of occult HBV infection in patients with HCV-related liver cirrhosis (LC) with or without HCC in São Paulo, Brazil. Serum and liver tissue samples from 50 hepatitis B surface antigen-negative patients with HCV-related LC who underwent liver transplantation at the University of São Paulo School of Medicine Hospital from 1993 to 2004 were divided into groups with LC only (N = 33) and with LC plus HCC (N = 17). HBV DNA was assayed for serum and paraffin-embedded liver tissue (tumoral and non-tumoral) using real time PCR and only 1 case with HCC had HBV DNA-positive serum. All liver samples were negative. HCV genotype 3 was detected in 17/39 (43.7%) cases. In conclusion, using a sensitive real time PCR directed to detect HBV variants circulating in Brazil, occult hepatitis B infection was not found among HCV-positive cirrhotic patients and was rarely found among HCV-positive HCC patients. These results are probably related to the low prevalence of HBV infection in our population. Furthermore, we have also shown that HCV genotype 3 is frequently found in Brazilian cirrhotic patients, particularly when they also have HCC. More studies involving a large number of cases should be carried out to confirm these data and to further characterize Brazilian HCV genotype isolates to elucidate genetic features that might be related to its carcinogenic potential.

High frequency of resistance to the drugs isoniazid and rifampicin among tuberculosis cases in the city of Cabo de Santo Agostinho, an urban area in Northeastern Brazil

The objective of the present study was to investigate the frequency and risk factors for developing multidrug-resistant tuberculosis in Cabo de Santo Agostinho, PE. This was a prospective study conducted from 2000 to 2003, in which suspected cases were investigated using bacilloscopy and culturing. Out of 232 confirmed cases of tuberculosis, culturing and antibiotic susceptibility tests were performed on 174. Thirty-five of the 174 cultures showed resistance to all drugs. The frequencies of primary and acquired resistance to any drug were 14% and 50% respectively, while the frequencies of primary and acquired multidrug resistance were 8.3% and 40%. Previous tuberculosis treatment and abandonment of treatment were risk factors for drug resistance. The high levels of primary and acquired resistance to the combination of isoniazid and rifampicin contributed towards the difficulties in controlling tuberculosis transmission in the city.

Study of the skin anatomy with high-frequency (22 MHz) ultrasonography and histological correlation

AbstractThe present essay is aimed at getting the radiologist familiar with the basic histological skin structure, allowing for a better correlation with sonographic findings. A high-frequency (22 MHz) ultrasonography apparatus was utilized in the present study. The histological analysis was performed after the skin specimens fixation with formalin, inclusion in paraffin blocks and subsequent staining with hematoxylin-eosin. The authors present a literature review showing the relationship between sonographic and histological findings in normal cutaneous tissue, and discuss the technique for a better performance of the sonographic scan. High-frequency ultrasonography is an excellent tool for the diagnosis of different skin conditions. However, as this method is operator-dependent, it is crucial to understand the normal skin structure as well as the correlation between histological and sonographic findings.

A high frequency electronic transducer for multiphase flow measurements

This paper describes an electronic transducer for multiphase flow measurement. Its high sensitivity, good signal to noise ratio and accuracy are achieved through an electrical impedance sensor with a special guard technique. The transducer consists of a wide bandwidth and high slew rate differentiator where the lead inductance and stray capacitance effects are compensated. The sensor edge effect is eliminated by using a guard electrode based on the virtual ground potential of the operational amplifier. A theoretical modeling and a calibration method are also presented. The results obtained seem to confirm the validity of the proposed technique.

High frequency of the CCR5delta32 variant among individuals from an admixed Brazilian population with sickle cell anemia

Homozygous sickle cell disease (SCD) has a wide spectrum of clinical manifestations. In Brazil, the main cause of death of individuals with SCD is recurrent infection. The CCR5delta32 allele, which confers relative resistance to macrophage-tropic HIV virus infection, probably has reached its frequency and world distribution due to other pathogens that target macrophage in European populations. In the present investigation a relatively higher prevalence (5.1%) of the CCR5delta32 allele was identified, by PCR amplification using specific primers, in 79 SCD patients when compared to healthy controls (1.3%) with the same ethnic background (Afro-Brazilians). Based on a hypothesis that considers SCD as a chronic inflammatory condition, and since the CCR5 chemokine receptor is involved in directing a Th1-type immune response, we suggest that a Th1/Th2 balance can influence the morbidity of SCD. If the presence of the null CCR5delta32 allele results in a reduction of the chronic inflammation state present in SCD patients, this could lead to differential survival of SCD individuals who are carriers of the CCR5delta32 allele. This differential survival could be due to the development of less severe infections and consequently reduced or less severe vaso-occlusive crises.

High frequency of mutation G377S in Brazilian type 3 Gaucher disease patients

Gaucher disease (GD), the most prevalent lysosome storage disorder, presents an autosomal recessive mode of inheritance. It is a paradigm for therapeutic intervention in medical genetics due to the existence of effective enzyme replacement therapy. We report here the analysis of GD in 262 unrelated Brazilian patients, carried out in order to establish the frequency of the most common mutations and to provide prognostic information based on genotype-phenotype correlations. Among 247 type 1 GD patients, mutation N370S was detected in 47% of all the alleles, but N370S/N370S homozygosity was found in only 10% of the patients, a much lower frequency than expected, suggesting that most individuals presenting this genotype may not receive medical attention. Recombinant alleles were detected at a high frequency: 44% of the chromosomes bearing mutation L444P had other mutations derived from the pseudogene sequence, present in 25% of patients. Three neuronopathic type 2 patients were homozygous for L444P, all presenting additional mutations (E326K or recombinant alleles) that probably lead to the more severe phenotypes. Six children, classified as type 1 GD patients, had a L444P/L444P genotype, showing that neuronopathic symptoms may only manifest later in life. This would indicate the need for a higher treatment dose during enzyme replacement therapy. Finally, mutation G377S was present in 4 homozygous type 1 patients and also in compound heterozygosity in 5 (42%) type 3 patients. These findings indicate that G377S cannot be unambiguously classified as mild and suggest an allele-dose effect for this mutation.

The effect of an aerobic training program on the electrical remodeling of the heart: high-frequency components of the signal-averaged electrocardiogram are predictors of the maximal aerobic power

Increased heart rate variability (HRV) and high-frequency content of the terminal region of the ventricular activation of signal-averaged ECG (SAECG) have been reported in athletes. The present study investigates HRV and SAECG parameters as predictors of maximal aerobic power (VO2max) in athletes. HRV, SAECG and VO2max were determined in 18 high-performance long-distance (25 ± 6 years; 17 males) runners 24 h after a training session. Clinical visits, ECG and VO2max determination were scheduled for all athletes during thew training period. A group of 18 untrained healthy volunteers matched for age, gender, and body surface area was included as controls. SAECG was acquired in the resting supine position for 15 min and processed to extract average RR interval (Mean-RR) and root mean squared standard deviation (RMSSD) of the difference of two consecutive normal RR intervals. SAECG variables analyzed in the vector magnitude with 40-250 Hz band-pass bi-directional filtering were: total and 40-µV terminal (LAS40) duration of ventricular activation, RMS voltage of total (RMST) and of the 40-ms terminal region of ventricular activation. Linear and multivariate stepwise logistic regressions oriented by inter-group comparisons were adjusted in significant variables in order to predict VO2max, with a P < 0.05 considered to be significant. VO2max correlated significantly (P < 0.05) with RMST (r = 0.77), Mean-RR (r = 0.62), RMSSD (r = 0.47), and LAS40 (r = -0.39). RMST was the independent predictor of VO2max. In athletes, HRV and high-frequency components of the SAECG correlate with VO2max and the high-frequency content of SAECG is an independent predictor of VO2max.

High-frequency electroacupuncture versus carprofen in an incisional pain model in rats

The objective of the present study was to compare the effect of electroacupuncture (EA) and carprofen (CP) on postoperative incisional pain using the plantar incision (PI) model in rats. A 1-cm longitudinal incision was made through skin, fascia and muscles of a hind paw of male Wistar rats and the development of mechanical and thermal hypersensitivity was determined over 4 days using the von Frey and Hargreaves methods, respectively. Based on the experimental treatments received on the third postoperative day, the animals were divided into the following groups: PI+CP (CP, 2 mg/kg, po); PI+EAST36 (100-Hz EA applied bilaterally at the Zusanli point (ST36)); PI+EANP (EA applied to a non-acupoint region); PI+IMMO (immobilization only); PI (vehicle). In the von Frey test, the PI+EAST36 group had higher withdrawal force thresholds in response to mechanical stimuli than the PI, PI+IMMO and PI+EANP groups at several times studied. Furthermore, the PI+EAST36 group showed paw withdrawal thresholds in response to mechanical stimuli that were similar to those of the PI+CP group. In the Hargreaves test, all groups had latencies higher than those observed with PI. The PI+EAST36 group was similar to the PI+IMMO, PI+EANP and PI+CP groups. We conclude that 100-Hz EA at the ST36 point, but not at non-acupoints, can reduce mechanical nociception in the rat model of incisional pain, and its effectiveness is comparable to that of carprofen.

Frequency of myocarditis in cases of fatal meningococcal infection in children: observations on 31 cases studied at autopsy

The frequency of myocarditis associated with meningococcal disease in children was reported only in two autopsied series (United States and South Africa). Here we report the frequency of associated myocarditis in 31 children who died of meningoccal infection at Hospital Infantil N.S. da Glória in Vitória, Espirito Santo State, Brazil. The diagnosis was confirmed by isolation of Neisseria meningitidis . At least three sections of fragments of both atria and ventricles were studied using the Dallas Criteria for the morphologic diagnosis of myocarditis. The mean age was 47.6 ± 39.8 months and the mean survival time after the onset of symptoms was 46.1 ± 26.5h (12-112h). Myocarditis was present in 13 (41.9%) patients, being of minimal severity in 11 cases and of moderate severity in 2 cases. There were no cases with severe diffuse myocarditis. The frequency of myocarditis was not influenced by sex, presence of meningitis, survival time after the onset of symptoms or use of vasoactive drugs. The frequency of myocarditis reported here was intermediate between the values reported in the only two case series published in the literature (57% in the United States and 27% in South Africa). Although our data confirm the high frequency of myocaditis in meningoccal disease, further investigations are necessary to elucidate the contribution of myocarditis to myocardial dysfunction observed in cases of meningococcal infection in children.

Updating the geographical distribution and frequency of Aedes albopictus in Brazil with remarks regarding its range in the Americas

The geographical distribution of Aedes albopictus in Brazil was updated according to the data recorded across the country over the last eight years. Countrywide house indexes (HI) for Ae. albopictus in urban and suburban areas were described for the first time using a sample of Brazilian municipalities. This mosquito is currently present in at least 59% of the Brazilian municipalities and in 24 of the 27 federal units (i.e., 26 states and the Federal District). In 34 Brazilian municipalities, the HI values for Ae. albopictus were higher than those recorded for Ae. aegypti, reaching figures as high as HI = 7.72 in the Southeast Region. Remarks regarding the current range of this mosquito species in the Americas are also presented. Nineteen American countries are currently infested and few mainland American countries have not confirmed the occurrence of Ae. albopictus. The large distribution and high frequency of Ae. albopictus in the Americas may become a critical factor in the spread of arboviruses like chikungunya in the new world.

Frequency of Fanconi anemia in Brazil and efficacy of screening for the FANCA 3788-3790del mutation

Fanconi anemia (FA) is an autosomal recessive genetic disease characterized by progressive bone marrow failure, susceptibility to cancer and multiple congenital anomalies. There is important clinical variability among patients and the knowledge of factors which might predict outcome would greatly help the decision making regarding the choices of treatment and the appropriate time to start it. Future studies of the possible correlation between specific mutations with specific clinical presentations will provide the answer to one of these factors. At our Center we standardized a rapid and precise screening test using a mismatch PCR assay for a specific mutation (3788-3790del in exon 38 of gene FANCA) in Brazilian FA patients. We present the results obtained after screening 80 non-consanguineous FA patients referred from all regions of Brazil with a clinical diagnosis of FA supported by cellular hypersensitivity to diepoxybutane. We were able to detect the 3788-3790del allele in 24 of the 80 (30%) FA patients studied. Thirteen of the 80 (16.25%) were homozygotes and 11 of the 80 (13.75%) were compound heterozygotes, thus confirming the high frequency of the FANCA 3788-3790del mutation in Brazilian FA patients. The identification of patients with specific mutations in the FA genes may lead to a better clinical description of this condition, also providing data for genotype-phenotype correlations, to a better understanding of the interaction of this specific mutation with other mutations in compound heterozygote patients, and ultimately to the right choices of treatment for each patient with improvement of the prognosis on future studies.

High prevalence of the GSTM3*A/B polymorphism in sub-Sarahan African populations

A 3-bp insertion/deletion polymorphism in intron 6 of GSTM3 (rs1799735, GSTM3*A/*B) affects the activity of the phase 2 xenobiotic metabolizing enzyme GSTM3 and has been associated with increased cancer risk. The GSTM3*B allele is rare or absent in Southeast Asians, occurs in 5-20% of Europeans but was detected in 80% of Bantu from South Africa. The wide genetic diversity among Africans led us to investigate whether the high frequency of GSTM3*B prevailed in other sub-Saharan African populations. In 168 healthy individuals from Angola, Mozambique and the São Tomé e Príncipe islands, the GSTM3*B allele was three times more frequent (0.74-0.78) than the GSTM3*A allele (0.22-0.26), with no significant differences in allele frequency across the three groups. We combined these data with previously published results to carry out a multidimensional scaling analysis, which provided a visualization of the worldwide population affinities based on the GSTM3 *A/*B polymorphism.