Resultados imediatos e a curto prazo do tratamento percutâneo do vazamento para protético / Immediate and short-term results of percutaneous leak treatment for prosthetic

INTRODUÇÃO: A regurgitação paraprotética (RPP) é um defeito que ocorre entre o local de sutura e o anel protético. A correção por transcateter tem surgido como uma opção à cirurgia para pacientes (pts) de alto risco. OBJETIVO: Avaliar os resultados imediatos e a curto prazo da oclusão da RPP por meio de cateter. MÉTODOS: Trata-se de um estudo prospectivo, de portadores de RPP, sintomáticos, submetidos a oclusão percutânea. O diagnóstico da RPP foi feito por meio da Doppler ecocardiografia TT e TE 3-D. O Critério de sucesso era: regurgitação residual discreta, melhora da classe funcional, regressão da hemólise e ausência de complicações fatais em até 30 dias. O critério de insucesso foi: complicações relacionadas ao procedimento, persistência de reflux moderado ou grave, hemólise, insuficiência cardíaca (IC) ou necessidade de cirurgia de urgência. RESULTADOS: Foram incluídos 20pts (24 próteses) com RPP, com média das idades de 61,5 anos, 11 pts femininos (55%). O número de cirurgias prévias variou de 1 a 4. A maioria (14) tinha 1 RPP, 5 tinham 2 e 1 tinha 4 orifícios regurgitantes. Cinco pts tinham prótese biológica (3 mitrais e 2 aórticas) e 15 próteses mecânicas (8 mitrais, 3 aórticas e 4 mitroaórticas). A indicação da intervenção foi a presença de IC com ou sem hemólise na maioria. A RPP foi grave em 16 pacientes, moderado em 3 e discreto em 1. A via de acesso percutâneo foi femoral em 17 pts. O dispositivo utilizado foi Amplatzer Vascular Plug, O número de plugs variou de 1a 4. Os pts foram distribuídos em 2 grupos: G1 (sucesso) e G2 (insucesso) segundo a definição acima. G1: o sucesso ocorreu em 13 dos 20pts (65%), 5 prótese biológica aórtica (100%) e 8 tinham prótese mecânica (53%) (5 mitrais e 3 aórticas). G2: insucesso ocorreu em 7 dos 20pts (35%), todos com prótese mecânica. Dois pts morreram antes da alta hospitalar (10%). Destes, um foi submetido a cirurgia de urgência por mal posicionamento do plug e o outro complicou com PCR e óbito. Cinco pts receberam alta hospitalar. Em uma evolução média de 14 meses, dos 13pts do G1, 3 morreram (1 acidente vascular cerebral hemorrágico, 1 infarto agudo do miocárdio e 1 IC descompensada); 10 estão evoluindo bem. Dentre os 5 pts do G2, 3 morreram, um continua em tratamento clínico e um foi operado. CONCLUSÃO: Em uma população de alto risco cirúrgico, a mortalidade relacionada a oclusão transcateter da RPP foi 10%. A resolução da RPP foi 65% e foi melhor nas próteses biológicas (100%) que nas mecânicas (53%).

Papel preditivo do escore de selvester em pacientes submetidos a troca transcateter de valva aórtica / Predictive role of selvester score in patients undergoing transcatheter aortic valve replacement

INTRODUÇÃO: O escore de Selvester é um escore eletrocardiográfico que estima e localiza a carga de fibrose miocárdica. Existem poucos dados sobre o impacto clínico da predição de fibrose em pacientes submetidos a troca transcateter de valva aórtica (TAVR). Este estudo avaliou o poder preditivo do escore de Selvester na sobrevida em pacientes com estenose aórtica (EA) submetidos a TAVR. MÉTODOS: Foram incluídos pacientes com estenose aórtica importante que realizaram eletrocardiograma pré-procedimento. Follow-up clínico foi obtido retrospectivamente. O desfecho primário foi morte por todas as causas e os secundários foram morte cardiovascular e MACE. RESULTADOS: 228 pacientes foram incluídos (idade média 81,5 ± 7,4 anos; 58,3% mulheres). Pacientes que morreram apresentaram escore de Selvester mais elevado (4,6 ± 3,2 vs. 1,4 ± 1,3; p < 0,001). Em um follow-up médio de 36,2 ± 21,2 meses, o escore de Selvester foi associado independentemente com mortalidade por todas as causas (HR, 1,65; 95% CI, 1,48-1,84; p < 0,001), mortalidade cardiovascular (HR, 1,59; 95% CI, 1,38-1,74; p < 0,001) e MACE (HR, 1,55; 95% CI, 1,30-1,68; p < 0,001). Após 5 anos, o risco de mortalidade foi diretamente correlacionado ao escore e o envolvimento da parede inferior do ventrículo esquerdo apresentou menor risco de mortalidade (HR, 0,42; 95% CI, 0,18-0,98; p = 0,046). Para o valor do escore de Selvester de 3, a área sobre a curva ROC foi de 0,92, 0,94 e 0,86 (p < 0,001) para 1, 2 e 3 anos, respectivamente. CONCLUSÃO: Valores elevados do escore de Selvester aumentam o risco de desfechos negativos em pacientes com EA submetidos a TAVR. O envolvimento das paredes anterior e lateral apresentam pior prognóstico.

Valvotomia percutânea com balão em pacientes com menos de 18 anos / Percutaneous balloon valvotomy in patients under 18 years

INTRODUÇÃO: Valvotomia mitral percutânea (VMP) é o tratamento de escolha em pacientes com estenose mitral reumática. Em pacientes jovens, o implante de uma prótese pode trazer diversas complicações no curto e longo prazo como durabilidade bastante reduzida. O OBJETIVO desse trabalho é descrever os resultados imediatos e acompanhar o follow-up desse grupo de pacientes. MÉTODOS: Foram selecionados, em uma coorte retrospectiva, pacientes que se submeteram a VMP com idade menor do que 18 anos devido a estenose mitral reumática. Os procedimentos e a ecocardiografia foram realizados em centro único. RESULTADOS: 58 pacientes (15,41±2,42 anos, 69% mulheres) foram submetidos a 66 procedimentos. A área valvar prévia foi de 0,87±1,94 cm2 e após o procedimento passou a ser 2,00±0,46cm2, com 74% de insuficiência mitral graduada como menor do que discreta, 98,5% tinham ritmo sinusal e o procedimento foi considerado sucesso em 89,4%, sucesso parcial em 6,1% e insucesso 4,5%. No acompanhamento de curto prazo, 19,7% evoluíram para necessidade de cirurgia, sendo 3% emergencial. 22 casos evoluíram para necessidade de redilatação, sendo 12 casos ainda com menos de 18 anos e os demais acima dessa idade. CONCLUSÃO: A VMP é o método de escolha para o tratamento da estenose mitral reumática em pacientes abaixo de 18 anos, de mostrando segurança e bons resultados. Nessa faixa etária a prevalência em homens foram significativamente superior.

Evolução da regurgitação tricúspide em pacientes submetidos a correção cirúrgica valvar mitral / Evolution of tricuspid regurgitation in patients undergoing mitral valve repair

INTRODUÇÃO: A insuficiência tricúspide (IT), na maioria dos casos, é secundária à doença da valva mitral associada à hipertensão arterial pulmonar (HP) e à fibrilação atrial (FA). Em geral, a IT regride com a correção da valva mitral. Porém, em alguns casos, mesmo corrigindo a mitral, a IT persiste ou evolui. Por esta razão, é controverso quando se deve realizar uma cirurgia combinada de correção da mitral e plástica tricúspide. OBJETIVO: Avaliar a evolução da IT em 10 anos após correção cirúrgica valvar mitral, com ou sem intervenção na tricúspide. MÉTODOS: Um trabalho prospectivo em pacientes (pts) submetidos a cirurgia para correção valvar mitral entre 2008 e 2009. A avaliação dos pts foi feita pela consulta clínica e Doppler-ecocardiograma Transtorácico até o ano de 2019. Os pts foram distribuídos em dois grupos, de acordo com o grau de IT no pré-operatório (pré-op): G1 (IT ausente/discreta) e G2 (IT moderada/grave). RESULTADOS: Foram incluídos 75 pts submetidos a correção mitral isolada ou combinada a plastia tricúspide. O G1 foi composto de 38 pts (51%) e o G2 de 37 pts (49%). No G1 foi realizada cirurgia combinada em 4 pts (10,5%) e todos permaneceram com IT discreta na evolução tardia; nos outros 34 foi feita cirurgia isolada; destes, 5 pts (14,7%) evoluíram para IT moderada/grave. No G2 a cirurgia combinada foi feita em 17 pts (45,9%). Na evolução tardia, 13 pts (77%) ficaram com IT mínima/discreta e 4 pts (23%) permaneceram com IT moderada/ grave. Dos 20 pts (54,1%) do G2 que fizeram cirurgia isolada, 13 (65%) tiveram involução da IT e em 7 (35%) a IT permaneceu moderada/grave. A evolução tardia dos 75 pts operados mostrou que o número de pts com IT discreta/moderada subiu de 38 para 59 e o número de pts com IT moderada /grave caiu de 37 para 16. Quando comparados, os pts que ficaram com IT moderada/grave eram mais velhos (46 x 49 anos) e tinham mais FA (35 x 38%); a média da HP (60 x 58mmHg) e da fração de ejeção foi semelhante nos dois grupos (61%). O número de cirurgia combinada foi 28,8% nos pts com IT discreta e 25% naqueles com IT moderada/grave. CONCLUSÃO: A correção da valva mitral não garante que a IT estabilize ou regrida, uma vez que em 14,7% dos pts com IT ausente/discreta no pré-op a IT evoluiu para moderada/grave e em 35% dos pts com IT moderada/grave a IT não regrediu. Houve falha da plástica tricúspide em 23% dos pts, que continuaram com IT moderada/grave no pós-operatório. A indicação de cirurgia combinada e o tipo de plástica realizada necessitam ser revistas nos pacientes portadores de doença mitral associada a IT.

Impacto tardio da hipertensão pulmonar e da insuficiência tricúspide após troca transcateter de valva aórtica / Late impact of pulmonary hypertension and tricuspid regurgitation after transcatheter aortic valve replacement

INTRODUÇÃO: Troca transcateter de valva aórtica (TAVR) é cada vez mais utilizada no tratamento da estenose aórtica (EA) senil. EA é comumente associada a hipertensão pulmonar (HP) e insuficiência tricúspide (IT). Nosso OBJETIVO foi avaliar o impacto tardio no curso da HP e IT. MÉTODOS: Pacientes submetidos a TAVR foram acompanhados quanto aos dados ecocardiográficos da HP e da IT por 24 meses. Todos os ecocardiogramas foram realizados em centro único. Foram divididos em grupos de acordo com IT e HP após 24 meses (pressão sistólica da artéria pulmonar = or < 45 mmHg) com follow-up de até 96 meses. Resultados clínicos e mortalidade foram comparados. RESULTADOS: 156 e 151 pacientes foram selecionados para acompanhamento da HP e da IT respectivamente. Média de follow-up foi de 42,23±17,53 meses e 42,60±17,67 meses para grupos de HP e IT. HP se reduziu após o TAVR (32,7% pre-TAVR vs. 20,5% pos-TAVR, p<0,001), mas não foi encontrada mudança significativa na IT (11,9% pre-TAVR vs. 10,6% pos-TAVR). Aumento de átrio esquerdo (AE) foi associado a manutenção de HP (p=0,002). Além disso, o aumento do diâmetro do AE (p=0,015) e EuroSCORE II elevado (p=0,041) foram correlacionados ao surgimento de nova HP. Na análise multivariada, surgimento de nova HP (HR 6,17, 95% CI 1,71­22,29,p=0,005), disfunção diastólica tipo II ou III (HR 1,06, 95% CI 1,06-1,11, p=0,036) e diâmetro de AE (HR 1,11, 95% CI 1,02­1,21, p=0,02) foram preditores independentes de mortalidade. CONCLUSÃO: TAVR foi capaz de reduzir a gravidade da HP, mas não da IT. Além disso, a sobrevida a longo prazo foi afetada pela HP, disfunção diastólica e tamanho do AE.

Who will be lost? Identifying patients at risk of loss to follow-up in Malawi. The DREAM Program Experience.

OBJECTIVES: Retention of subjects in HIV treatment programmes is crucial for the success of treatment. We evaluated retention/loss to follow-up (LTFU) in subjects receiving established care in Malawi. METHODS: Data for HIV-positive patients registered in Drug Resource Enhancement Against AIDS and Malnutrition centres in Malawi prior to 2014 were reviewed. Visits entailing HIV testing/counselling, laboratory evaluations, nutritional evaluation/supplementation, community support, peer education, and antiretroviral (ART) monitoring/pharmacy were noted. LTFU was defined as > 90 days without an encounter. Parameters potentially associated with LTFU were explored, with univariate/multivariate logistic regression analyses being performed. RESULTS: Fifteen thousand and ninety-nine patients registered before 2014; 202 (1.3%) were lost to follow-up (LTFU) (1.3%). Nine (0.5%) of 1744 paediatric patients were LTFU vs. 1.4% (n = 193) of 13 355 adults (P < 0.001). Subjects who were LTFU had fewer days in care than retained subjects (1338 vs. 1544, respectively; P < 0.001) and a longer duration of ART (1530 vs. 1300 days, respectively; P < 0.001). Subjects who were LTFU had higher baseline HIV viral loads (P = 0.016) and higher body mass indexes (P < 0.001), were more likely to live in urban settings (88% of patients who were LTFU lived in urban settings) with better housing [relative risk (RR) 2.3; 95% confidence interval (CI) 1.67-3.09; P < 0.001], and were more likely to be educated (RR 1.88; 95% CI 1.42-2.50; P < 0.001). Distance to the centre and cost of transportation were associated with LTFU (RR 3.4; 95% CI 2.84-5.37; P < 0.001), as was absence of a maternal figure (RR 1.57; 95% CI 1.17-2.09; P < 0.001). Viral load, distance index, education and a maternal figure were predictive of LTFU. CONCLUSIONS: Educated, urbanized HIV-infected adults living far from programme centres are at high risk of LTFU, particularly if there is no maternal figure in the household. These variables must be taken into consideration when developing retention strategies.

Asymptomatic carotid stenosis is associated with gray and white matter damage.

BACKGROUND: Cognitive deficits in patients with asymptomatic carotid stenosis have been reported. The ultimate mechanism of cognitive deficits remains unclear and might be related to subtle structural brain damage. AIMS: The aim of the present study was to evaluate the presence of subtle white and grey matter abnormalities associated with asymptomatic carotid stenosis. METHODS: Twenty-five patients with asymptomatic ≥70%/occlusion carotid stenosis and 25 healthy controls, matched for gender and age, underwent 3 Tesla brain magnetic resonance imaging. Gray and white matter macrostructural abnormalities were evaluated with voxel-based morphometry using spm8 software. White matter microstructural abnormalities were evaluated with diffusion tensor images with the Diffusion Toolbox package and tract-based spatial statistics from FMRIB Software Library. RESULTS: We observed significant macro- and microstructural white matter abnormalities, and these findings were diffuse and symmetrical in both hemispheres. In contrast, gray matter atrophy was observed in the areas corresponding to the anterior circulation of the hemisphere ipsilateral to the carotid stenosis. CONCLUSIONS: Patients with asymptomatic carotid stenosis have different patterns of gray and white matter abnormalities. While the white matter damage is diffuse, the gray matter atrophy is localized in the territory of anterior circulation ipsilateral to the stenosis. The role of asymptomatic carotid stenosis in the gray matter damage must be further investigated with longitudinal studies and comparison with neuropsychological evaluation.

Magnetically controlled single-nanoparticle detection via particle-electrode collisions.

This paper reports the magnetic control of nanoparticle collisions on gold ultramicroelectrode surface. Magnetite nanoparticles with diameters of 10 nm and modified with Prussian blue (Fe3O4-NPs-PB) were directed by gravitational force on the electrode surface, and spikes in current-time transients were observed. By modulating a magnetic field parallel to the electrode surface, the number of nanoparticle collisions and the nanoparticle positions could be controlled.

The impact of integrating food supplementation, nutritional education and HAART (Highly Active Antiretroviral Therapy) on the nutritional status of patients living with HIV/AIDS in Mozambique: results from the DREAM Programme.

DREAM (Drug Resources Enhancement against AIDS and Malnutrition) is a multiregional health program active in Mozambique since 2002 and provides free of charge an integrating package of care consisting of peer to peer nutritional and health education, food supplementation, voluntary counseling and testing, immunological, virological, clinical assessment and HAART (Highly Active AntiRetroviral Treatment). The main goals of this paper are to describe the state of health and nutrition and the adequacy of the diet of a sample of HIV/AIDS patients in Mozambique on HAART and not. A single-arm retrospective cohort study was conducted. 106 HIV/AIDS adult patients (84 in HAART), all receiving food supplementation and peer-to-peer nutritional education, were randomly recruited in Mozambique in two public health centres where DREAM is running. The programme is characterized by: provision of HAART, clinical and laboratory monitoring, peer to peer health and nutritional education and food supplementation. We measured BMI, haemoglobin, viral load, CD4 count at baseline (T0) and after at least 1 year (T1). Dietary intake was estimated using 24h food recall and dietary diversity was assessed by using the Dietary Diversity Score (DDS) at T1. Overall, the patients'diet appeared to be quite balanced in nutrients. In the cohort not in HAART the mean BMI values showed an increases but not significant (initial value: 21.9 ± 2.9; final value: 22.5 ± 3.3 ) and the mean haemoglobin values (g/dl) showed a significant increases (initial value: 10.5+ 2.1; final value: 11.5 ± 1.7 p< 0.024) . In the cohort in HAART, both the mean of BMI value (initial value: 20.7 ± 3.9; final value: 21.9 ± 3.3 p< 0.001) and of haemoglobin (initial value: 9.9 ± 2.2; final value: 10.8 ± 1.7 p< 0.001) showed a higher significant increase. The increase in BMI was statistically associated with the DDS in HAART patients. In conclusion nutritional status improvement was observed in both cohorts. The improvement in BMI was significant and substantially higher in HAART patients because of the impact of HAART on nutritional status of AIDS patients. Subjects on HAART and with a DDS > 5, showed a substantial BMI gain. This association showed an additional expression of the synergic effect of integrating food supplementation, nutritional education and HAART on the nutritional status of African AIDS patients and also highlights the complementary role of an adequate and diversified diet in persons living with HIV/AIDS in resources limited settings.

L-Arginine administration during rat brain development facilitates spreading depression propagation: evidence for a dose- and nutrition-dependent effect.

L-Arginine (ARG) is the precursor of the nitric oxide (NO) synthesis. NO-mediated signaling seems to be involved in the phenomenon of cortical spreading depression (CSD). Here, well-nourished and malnourished rats were treated, by gavage, with 150, 300 or 450 mg/kg/day of L-arginine from postnatal days 7-28, and CSD propagation was analyzed at 30-40 days. Compared to non-treated ('naïve') and water-treated controls, ARG-treated rats dose-dependently displayed higher CSD-velocities (P<0.05). In the malnourished rats, only the highest ARG-dose (450 mg/kg/day) increased CSD velocities. The mean +/- SD CSD-velocities (in mm/min) were: for well-nourished rats, 3.77 +/- 0.15, 3.78 +/- 0.23, 4.03 +/- 0.16, 4.36 +/- 0.19 and 4.41 +/- 0.26, in the naïve-, water-controls, 150, 300 and 450 mg/kg/day ARG-groups, respectively; for the same conditions in the malnourished rats, the velocities were 4.18 +/- 0.13, 4.22 +/- 0.09, 4.24 +/- 0.10, 4.27 +/- 0.21 and 4.64 +/- 0.22, respectively. Results demonstrate a dose- and nutrition-dependent CSD-facilitation by L-arginine administered during brain development. It is suggested that this effect is due to the modulation of nitric oxide synthesis.

The DREAM model's effectiveness in health promotion of AIDS patients in Africa.

This study evaluates the effectiveness of a holistic model for treating people living with AIDS in Africa; the model aims to improve knowledge about AIDS prevention and care, increase trust in the health centre, impact behaviour, and promote a high level of adherence to HAART. The study took place in the context of the DREAM (Drug Resource Enhancement against AIDS and Malnutrition) programme in Mozambique, designed by the Community of Sant'Egidio to treat HIV patients in Africa. It provides patients with free anti-retroviral drugs, laboratory tests (including viral load), home care and nutritional support. This is a prospective study involving 531 patients over a 12-month period. The patients, predominantly poor and with a low level of education, demonstrated a good level of knowledge about AIDS (more than 90% know how it is transmitted) and trust in the treatment, with a relatively small percentage turning to traditional healers. Overall the patients had a low level of engaging in risky sexual behaviour and a very good level of adherence to HAART (69.5% of the 531 subjects had a pill count higher than 95%). The positive results of the programme's educational initiatives were confirmed with the patients' good clinical results.

Gastrointestinal dysfunction in mice with a targeted mutation in the gene encoding vasoactive intestinal polypeptide: a model for the study of intestinal ileus and Hirschsprung's disease.

In 1970, Drs. Said and Mutt isolated a novel peptide from porcine intestinal extracts with powerful vasoactive properties, and named it vasoactive intestinal peptide (VIP). Since then, the biological actions of VIP in the gut as well as its signal transduction pathways have been extensively studied. A variety of in vitro and in vivo studies have indicated that VIP, expressed in intrinsic non-adrenergic non-cholinergic (NANC) neurons, is a potent regulator of gastrointestinal (GI) motility, water absorption and ion flux, mucus secretion and immune homeostasis. These VIP actions are believed to be mediated mainly by interactions with highly expressed VPAC(1) receptors and the production of nitric oxide (NO). Furthermore, VIP has been implicated in numerous physiopathological conditions affecting the human gut, including pancreatic endocrine tumors secreting VIP (VIPomas), insulin-dependent diabetes, Hirschsprung's disease, and inflammatory bowel syndromes such as Crohn's disease and ulcerative colitis. To further understand the physiological roles of VIP on the GI tract, we have begun to analyze the anatomical and physiological phenotype of C57BL/6 mice lacking the VIP gene. Herein, we demonstrate that the overall intestinal morphology and light microscopic structure is significantly altered in VIP(-/-) mice. Macroscopically there is an overall increase in weight, and decrease in length of the bowel compared to wild type (WT) controls. Microscopically, the phenotype was characterized by thickening of smooth muscle layers, increased villi length, and higher abundance of goblet cells. Alcian blue staining indicated that the latter cells were deficient in mucus secretion in VIP(-/-) mice. The differences became more pronounced from the duodenum to the distal jejunum or ileum of the small bowel but, became much less apparent or absent in the colon with the exception of mucus secretion defects. Further examination of the small intestine revealed larger axonal trunks and unusual unstained patches in myenteric plexus. Physiologically, the VIP(-/-) mice showed an impairment in intestinal transit. Moreover, unlike WT C57BL/6 mice, a significant percentage of VIP(-/-) mice died in the first postnatal year with overt stenosis of the gut.

Seroprevalence of HHV8 in a cohort of HIV-negative and HIV-positive patients in Mozambique.

Kaposi Sarcoma shows several different clinical and epidemiological patterns. In Sub-Saharan Africa, where the HIV achieves an high prevalence of infection, the KS can be found both in HIV positive than in HIV negative patients, and the diffusion of the HHV8 virus is endemic. The aim of the work is to evaluate the HHV8 seroprevalence in Mozambique. Moreover the relationship of some main indicators, as CD4 and CD8 cells count, HIV viral load, Body Mass Index and haemoglobin values have been calculated in a part of the DREAM Cohort, (HIV positive patients enrolled in the Community of Sant'Egidio program to fight AIDS in the Sub-Saharan Africa). In the HIV positive cohort HHV8 negative and HHV8 positive groups show statistical significance (p < 0.05) in CD4 cells count, a strong significance (p = 0.01) in CD8 cells count and a significance also in Haemoglobin levels (p = 0.35). The difference in Haemoglobin levels (0.5 g/dl) is related more to a statistical than a clinical significance. The study confirms the free circulation of the HHV8 virus in the Mozambican population, with a prevalence rate of 51.1%, similar than that measured in bordering countries. Considering the CD8 value within the HIV positive sub-cohort a strong correlation with the positivity for HHV8 and the immunological status is suggested.

Pediatric highly active antiretroviral therapy in Mozambique: an integrated model of care.

AIM: To test the impact of a public health model to implement HIV pediatric care in Limited Resource Settings. METHODS: A retrospective study on the clinical files of 679 Mozambican children (mean age 4.4 years; SD 3.2), has been carried out. The pediatric patients received HAART (Highly Active Anti-Retroviral Therapy) in the framework of DREAM, a nationwide public health program offering an integrated model of care to HIV patients including free-of-charge HAART and monitoring, nutritional assessment and supplementation, peer-to-peer education, active tracing of the dropped out patients. RESULTS: HAART was started in 297 subjects out of 679. The median time of treatment was 286 (IQ 25-75:125-465). Mortality rate was lower in the sub-sample receiving HAART (8.4%; CI 95%: 5.2-11.6 vs 13.1%; CI 95%: 9.7-16.5). After 6 months of treatment the percentage of viral load lower than 400 copies/mL rose from 4.9% to 46.3%. The percentage of patients with less than 15% of CD4 cells out of the total lymphocyte count and the percentage of patients below the 2 z-score decreased from 56.4% and 58.1% to 8.8% and 38.1% respectively. CONCLUSIONS: Pediatric HAART in limited resource settings often face difficulties to handle complex treatment schemes, but the implemented model seems to be an effective tool to reduce mortality rate in HIV positive pediatric population.

Safety of nevirapine-containing antiretroviral triple therapy regimens to prevent vertical transmission in an African cohort of HIV-1-infected pregnant women.

OBJECTIVE: To assess the incidence and consequences of adverse reactions among African HIV-positive pregnant women treated with fixed-dose combinations of a nevirapine-containing antiretroviral (ARV) triple therapy. METHODS: A retrospective analysis of the clinical files of 703 HIV-1-positive pregnant women treated with a nevirapine-containing regimen between May 2002 and July 2004 was conducted. Selection criteria for inclusion in the analysis were: (a) taking ARV for more than 14 days; (b) baseline values of transaminases below the threshold of 2.5 times the upper limit of normal (ULN). The women were on a nevirapine-containing regimen for a median of 127 days [interquartile range (IQR) 86-190 days], starting on average at the 27th week of gestation (standard deviation+/-9.5) and continuing up to a maximum of 6 months after delivery. All women were offered formula milk to feed the babies. Highly active antiretroviral therapy (HAART) was continued beyond 6 months only if the patient qualified on the first visit. The main outcome measures were incidence of hepatotoxicity, skin rashes and Stevens-Johnson syndrome. Multivariate analysis to assess the impact of several factors on the adverse reaction rate was performed. RESULTS: As of 1 August 2004, 554 pregnancies reached term, 96 women were still pregnant, and 53 women dropped out of the programme before giving birth. After 2 months of therapy the percentage of patients with a viral load less than 1000 HIV-1 RNA copies/mL increased to 78.6%; average CD4 cell counts increased from 490 cells/microL before therapy to 630 after therapy. The incidence of grade 3-4 adverse reactions (hepatotoxicity, skin rashes and Stevens-Johnson syndrome) was 6.5, 2.4 and 1.1%, respectively. Five women died during pregnancy (0.88%). Only one of the deaths could be associated with ARV treatment. CONCLUSION: Nevirapine-containing regimens in pregnant woman, at all CD4 cell count levels, appear to be safe in African settings.

Improving adherence to highly active anti-retroviral therapy in Africa: the DREAM programme in Mozambique.

Ensuring high levels of adherence to highly active anti-retroviral therapy (HAART) is a priority in treating people living with AIDS. This study reports the rates of adherence of patients served by DREAM (Drug Resource Enhancement against AIDS and Malnutrition) in the city of Matola, Mozambique. DREAM, an innovative programme tailored for Africa, was implemented by the Community of Sant'Egidio in August 2001. DREAM provides patients with anti-retroviral drugs and laboratory tests at no charge, and is based on a particular strategy of health education and organization of services designed for a population that is predominantly poor and has a low level of formal education. This study analyzes the adherence of 154 patients over a period of 6 months. In evaluating adherence, two indicators were used: (1) the percentage of appointments kept for check-ups, tests and the collection of medicine, and (2) the overall change in the patients' blood chemistry over the 6-month period. Of the 154 patients, 127 (82.5%) kept more than 90% of their appointments. Adherence to the programme was further confirmed by a relevant increase of hemoglobin levels and CD4 counts, and a significant decrease in the viral loads among the 154 patients.

Characterization of the pharmacology, signal transduction and internalization of the fluorescent PACAP ligand, fluor-PACAP, on NIH/3T3 cells expressing PAC1.

Fluor-PACAP, a fluorescent derivative of PACAP-27, has been confirmed to share a high affinity for PAC1 receptors transfected into NIH/3T3 cells and to have comparable pharmacological characteristics to the unconjugated, native form. Through competitive binding with 125I-PACAP-27, the two ligands exhibited similar dose- dependent inhibition. Additional examination of the efficacy of activating adenylyl cyclase revealed that both ligands analogously stimulated the production of cyclic AMP. Furthermore, PAC1 internalization visualized by our Fluor-PACAP, is compareable to that performed with the radioligand, 125I-PACAP-27, with maximal internalization achieved within thirty minutes. Thus, Fluor-PACAP exhibits intracellular signaling abilities homologous to the native ligand.

Inactivated suckling mouse brain rabies vaccine provides short-term immunity in capuchin monkeys (Cebus apella).

Eight capuchin monkeys (Cebus apella) were vaccinated against rabies with an inactivated suckling mouse brain vaccine (SMBV). Three 1-ml doses of 2% brain tissue suspension were given by i.m. injection at 0, 30, and 60 days. Blood samples were collected at 0, 30, 60, 90, 150, 210, 240, 300, and 365 days and were tested by simplified fluorescence inhibition to titer-neutralizing antibodies. All of the animals developed neutralizing antibodies with titers >0.5 IU/ml after vaccination, but the immune response persisted for only 122.3 +/- 32.6 days. The SMBV was able to induce immune response in the capuchin monkeys, but protection was short-lived.