HBV/HDV co-infection in the Western Brazilian Amazonia: an intriguing mutation among HDV genotype 3 carriers.

HDV infection still remains a serious public health problem in Amazonia. There are few data regarding the biomolecular aspects of HBV/HDV co-infection in this region. We studied 92 patients HBsAg(+) /anti-HDV IgG(+) followed at the Hepatitis Referral Centers of Porto Velho (RO), Rio Branco and Cruzeiro do Sul (AC), Brazil, from March 2006 to March 2007 for whom the HDV and/or the HBV genotype could be determined. The HDV genotype could be determined in 90 patients, while the HBV genotypes could be positively determined in 74. HBV subgenotype F2 is the most prevalent (40.2%), followed by the subgenotypes A1 (15.2%) and D3 (8.7%), while 16.4% were other subgenotypes or genotypes, 4.3% were discordant and 15.2% were unamplifiable. Surprisingly, HDV genotype 3 (HDV-3) was found in all of the HBV/HDV-infected patients that could be genotyped for HDV, confirming that HDV-3 can associate with non-F HBV genotypes. However, a HDV-3 mutant was found in 29.3% of patients and was more frequently associated with non-F HBV genotypes (P < 0.001) than were nonmutant strains, suggesting that the mutation may facilitate association of HDV-3 with non-F HBV genotypes.

The epidemiology of malaria in Rondonia (Western Amazon region, Brazil): study of a riverine population.

We report on a longitudinal study concerning the incidence of malaria in a riverine population (Portuchuelo) settled on the riverbanks of Rio Madeira, in the State of Rondonia, Brazil. We found the incidence of malaria to be seasonal, prevailing in the dry months of June and July. The Annual Parasite Index (API) was 292/1000 inhabitants, almost three times that of the state of Rondonia for the same period. In contrast with other studied Rondonian populations, malaria in Portuchuelo was more prevalent in youngsters < 16 years old, particularly in the 0-1 year age group. Adults were relatively spared, particularly those over 50 years. Besides being indicative of indoor transmission, these facts may suggest the existence of a certain degree of acquired resistance to infection and/or of lessened symptoms in older people. Riverine populations are spread over the entire Amazon region where most of its members were born. Due to the permanent presence of malaria among riverine populations, we are proposing that they may act as perennial reserves of malaria and, therefore, as sources of infection for migrants or eventual settlers at their vicinity. To date, the opposite view has been generally held. Anopheles darlingi, the main vector species in the area, is essentially sylvatic, which contributes to make the control of malaria highly problematic. The only hopes for control rest on permanent surveillance and the prompt treatment of patients, which are also problematic considering the vastness of the Amazon region and the remoteness of some of its riverine settlements.

[Guidelines of the Spanish Society of Cardiology on requirements and equipment in hemodynamic and interventional cardiology]. / Guías de práctica clínica de la Sociedad Española de Cardiología sobre requerimientos y equipamiento en hemodinámica y cardiología intervencionista.

In the last 20 years the work performed in catheterization laboratories has changed greatly, and while also taking the diagnostic aspects also into account, interventional cardiology has acquired an important role. Work in the catheterisation laboratory has evolved from only diagnostic studies of cardiac anatomy and function, and evaluation of potential surgical candidates, to interventional procedures mainly based on catheters techniques. As new diagnostic and interventional procedures are now available, human and technical requirements of the catheterization laboratory have changed. The aim of this report is to make an update of the requirements needed to perform diagnostic and interventional procedures in the cardiac catheterization laboratory.

[Clinical and angiographic expression of myocardial ischemia in stable angina as a function of its coronary reserve]. / Expresión clínica y angiográfica de la isquemia miocárdica en la angina estable en función de su reserva coronaria.

We have studied the distribution of the coronary reserve, evaluated by serial effort tests, in patients with proved coronaropathy, determining the correlation between clinic (effort and mixed angina) and coronary reserve (fixed and variable), assessing angiographic findings in function to that reserve. We took 120 patients with stable angina to whom 2 effort tests were performed, basal and after vasodilator drugs. It was considered variable reserve if in the second test the S-T descend improved greater than or equal to 1 mm for a similar of greater double product and fixed when it didn't improve. In all patients coronarography was performed. Seventy two patients (60%) showed fixed reserve, 58 with effort angina (80%) and 14 (20%) with mixed. Forty eight showed variable reserve, 40 (80%) with mixed angina and 8 (17%) with effort. The group with fixed reserve had a greater S-T max. descent (2.9 +/- 0.9 vs 2.2 +/- 0.4) (p less than 0.001), a lower double product max. (221 +/- 44 vs 284 +/- 37) (p less than 0.001) and a lower maximal oxygen consumption (MVO2 7 +/- 2 vs 11 +/- 2) (p less than 0.001) than the variable reserve group. Considering the angiography, the fixed reserve group had more number of vessels affected (1.9 +/- 0.7 vs 1.4 +/- 0.5) (p less than 0.01), a higher angiographic score (4.88 +/- 2.4 vs 2.2 +/- 1.2) (p less than 0.001), a lower ejection fraction (59 +/- 8.5 vs 65 +/- 7.5) (p less than 0.001), more multivessel and descending anterior artery lesion than the variable reserve group.(ABSTRACT TRUNCATED AT 250 WORDS)

[The evaluation of the efficacy of artesunate combined with tetracycline in the therapy of falciparum malaria]. / Avaliação da eficácia do artesunato associado à tetraciclina na terapêutica da malária falciparum.

A controlled clinical therapeutic study in hospitalized patients compared artesunate with quinine and mefloquine in patients with uncomplicated falciparum malaria. Forty two patients entered the trial and the follow up was for 28 days with thick blood film taken every 12 hours until became negative. Laboratory examinations included haematological and biochemical tests before and after treatment. Patients had a mean parasitaemia of 42.568 per microliter. Twenty six patients completed 28 days of follow up but 16 did not fulfil this protocol. One in each of the therapeutic groups showed delayed R I resistance. A further patient in the quinine group showed R III resistance. The cure rate was 88.8% for artesunate. 85.7% for mefloquine and 81.8% for quinine; no significant difference was found, the same occurring with the clearance of fever. The artesunate group had a quicker parasitaemia clearance time (37.3 +/- 11.5 hours) when compared with quinine (65.2 +/- 17.4) showing a significant difference (p = 0.0016). Parasite clearance with mefloquine, was intermediate (58.9 +/- 16.6 ours) between the artesunate and quinine. No important side effects were observed with any of the therapeutic regimens and no deaths registered.

Identification of the NF-κB inhibitor A20 as a key regulator for human adipogenesis.

The zinc-finger protein A20 is a key player in the negative feedback regulation of the nuclear factor kappa-light-chain-enhancer of activated B-cell (NF-κB) pathway in response to multiple stimuli. Tumor necrosis factor alpha (TNFα), a cytokine with pleiotropic effects on cellular proliferation and differentiation, dramatically increases A20 expression in all tissues. As TNFα inhibits adipocyte differentiation, we have determined the contribution of A20 to the adipogenic capacity of human mesenchymal stromal cells (MSCs). Here we show that A20 is constitutively expressed in MSCs, which previously has been observed only in cells that are either tumor or immune cells (T/B lymphocytes). TNFα stimulation induced a rapid degradation of A20 protein mediated exclusively by the proteasome in MSCs and not by caspases. This degradation is concomitant to the induction of its own mRNA, which suggests that a tight regulation of NF-κB signaling in MSCs is fundamental. On one hand, we demonstrate that the knockdown of A20-mediated transcript dramatically decreases the adipogenic capacity of MSCs, which correlates with the phenotype observed in the presence of TNFα. On the other hand, A20 overexpression blocks NF-κB activation and drives to increased adipogenesis, even in the presence of TNFα treatment. In conclusion, our data demonstrate that the presence of A20 allows MSCs to differentiate into adipocytes by maintaining NF-κB signaling at a basal state.

[Descriptive study about physical examination patterns of a Spanish physician's sample]. / Estudio descriptivo sobre patrones de exploración física de una muestra de médicos españoles.

BACKGROUND AND OBJECTIVES: We describe the basic scheme of physical examination (PE) and the patterns of PE by specialties. We compare items explored by internists and family physicians. PATIENTS AND METHOD: A cross-sectional study on the routine physical examination made by a Spanish physician's sample. Seventy-six maneuvres were analysed by a table of frequencies obtaining physical examination patterns by specialties. RESULTS: A total of 131 physicians of 140 answered the questionnaire (93.5%). They corresponded to Internal Medicine (48.1%), Family and General Medicine (32.1%), other specialties (19.8%). Average age of responders was 37.8 years (Confidence Interval [CI] 95%: 36.3-39.4) and years of experience average were 11.9 (CI 95%: 10.4-13.5). The pattern of general examination used by more than 70% of the physicians surveyed includes maneuvres related to the general examination, respiratory, cardio-circulatory, gastro-intestinal and neurological systems examination. Internists explore weight, temperature, cardiac rate, arterial pressure, neck, jugular ingurgitation, respiratory, abdominal and lymphatic system more often than family physicians (p<0.05). Family physicians perform otoscopy and nose, conches and nasal septum inspection more often than internists (p<0.05). CONCLUSIONS: PE is a flexible tool physicians adapt to their needs based on the specialty they have. Internists are the specialists who make a more exhaustive physical examination compared with family physicians and other specialists.

Malaria control in an agro-industrial settlement of Rondônia (Western Amazon region, Brazil).

A malaria control pilot project was developed in the Urupá agro-industrial farm that is situated in the State of Rondônia (Western Amazon Region, Brazil). Around 180 inhabitants had been surveyed for the past five years. The control measures were based on (1) training a community agent to perform on the spot microscopical diagnosis of malaria and to treat the uncomplicated cases of malaria; (2) limiting the use of insecticides to a short period before the high transmission season. This resulted in a significant reduction in the time between the onset of clinical symptoms and specific chemotherapy which fell from 3.5 to 1.3 days. In relation to the previous three reference years the total number of malaria cases was reduced to 50% in the first year and to 25% in the second year. The introduction of these measures coincided with pronounced reduction in the frequency of Plasmodium falciparum infections but this was less marked for P. vivax infections. In the second year of the pilot experiment there was no P. falciparum transmission on the farm. During the last decade there was a general decrease in the endemicity of malaria in the State of Rondônia. The linear regression coefficient values indicate that the decline was more pronounced in Urupá than in the general municipality and that the falciparum malaria API in Urupá farm is significantly lower than in the general municipality of Candeias were the farm is situated.

In-vivo sensitivity of Plasmodium vivax isolates from Rond nia (western Amazon region, Brazil) to regimens including chloroquine and primaquine.

Seventy-nine adults with Plasmodium vivax malaria, from the Porto Velho area of Rond nia (western Amazon region, Brazil), gave informed consent to participate in a blind, clinical study of two regimens of treatment with chloroquine (CQ) and primaquine. The effectiveness of the 'classical' regimen (CQ for 3 days, followed by primaquine for 14 days) was compared with that of a 'short' regimen in which the two drugs were given simultaneously for 5 days. There were no cases of recrudescence indicative of CQ resistance (i.e. within 30 days of the first treatment dose) among the 73 patients who each completed a full, supervised course of treatment. However, 10 cases of apparent relapse were observed (all > 60 days after first treatment dose), representing 6.5% (2/31) of the patients who completed 60 days of follow-up after the classical treatment and 26.7% (8/30) of the short-regimen patients who completed the same period of follow-up. PCR-based comparison of parasitic DNA collected pre- and post-treatment was successful for eight of the 10 cases of apparent relapse and indicated that two such cases, both given the short regimen of treatment, were, in fact, probable cases of re-infection rather than of relapse. The results indicate that the classical schedule of treatment with chloroquine and primaquine was more effective at preventing relapses than the short regimen. However, since prolonged treatment with primaquine often produces side-effects that are severe enough to reduce compliance, the short schedule could be a useful alternative for malaria control in endemic areas of the Amazon region.

Avaliação da eficácia do artesunato associado à tetraciclina na terapêutica da malária falciparum / The evaluation of the efficacy of artesunate combined with tetracycline in the therapy of falciparum malaria

Realizou-se um ensaio clínico, randomizado e controlado, comparando o artesunato com o quinino e a mefloquina, em casos de malária não grave. Foram tratados 42 pacientes em regime de internação e o seguimento durou 28 dias. Realizou-se exame de gota espessa cada 12 horas até sua negativação, hemograma e bioquímica sanguínea, pré e pós-tratamento. A média da parasitemia inicial foi 42.568 parasitas/ml. Vinte e seis pacientes foram acompanhados durante 28 dias e 16 durante menos de 28 dias. Um paciente de cada grupo apresentou R I tardia e um paciente do grupo do quinino apresentou R III. As porcentagens de cura foram 88,8%, 85,7% e 81,8% para o artesunato, a mefloquina e o quinino, respectivamente, sem mostrar diferença significativa. O tempo de desaparecimento da febre não mostrou diferença significativa entre os grupos. O grupo do artesunato teve um tempo menor de clareamento da parasitemia (37,33 ± 11,52 horas) quando comparado com o quinino (65,25 ± 17,44 horas), sendo estatisticamente significativa (p = 0,0016). O grupo da mefloquina (58,9 ± 16,68 horas) não mostrou diferença com os outros grupos. Não se apresentaram efeitos adversos importantes em nenhum dos esquemas usados, sendo bem tolerados pelos pacientes.

A controlled clinical therapeutic study in hospitalized patients compared artesunate with quinine and mefloquine in patients with uncomplicated falciparum malaria. Forty two patients entered the trial and the follow up was for 28 days with thick blood film taken every 12 hours until became negative. Laboratory examinations included haematological and biochemical tests before and after treatment. Patients had a mean parasitaemia of 42.568 per microliter. Twenty six patients completed 28 days of follow up but 16 did not fulfil this protocol. One in each of the therapeutic groups showed delayed R I resistance. A further patient in the quinine group showed R III resistance. The cure rate was 88.8% for artesunate. 85.7% for mefloquine and 81.8% for quinine; no significant difference was found, the same occurring with the clearance of fever. The artesunate group had a quicker parasitaemia clearance time (37.3 +/- 11.5 hours) when compared with quinine (65.2 +/- 17.4) showing a significant difference (p = 0.0016). Parasite clearance with mefloquine, was intermediate (58.9 +/- 16.6 ours) between the artesunate and quinine. No important side effects were observed with any of the therapeutic regimens and no deaths registered.