Intravenous Busulfan for Autologous Stem Cell Transplantation in Adult Patients with Acute Myeloid Leukemia: a Survey of 952 Patients on Behalf of the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation

Oral busulfan is the historical backbone of the busulfan+cyclophosphamide regimen for autologous stem cell transplantation. However intravenous busulfan has more predictable pharmacokinetics and less toxicity than oral busulfan; we, therefore, retrospectively analyzed data from 952 patients with acute myeloid leukemia who received intravenous busulfan for autologous stem cell transplantation. Most patients were male (n=531, 56%), and the median age at transplantation was 50.5 years. Two-year overall survival, leukemia-free survival, and relapse incidence were 67±2%, 53±2%, and 40±2%, respectively. The non-relapse mortality rate at 2 years was 7±1%. Five patients died from veno-occlusive disease. Overall leukemia-free survival and relapse incidence at 2 years did not differ significantly between the 815 patients transplanted in first complete remission (52±2% and 40±2%, respectively) and the 137 patients transplanted in second complete remission (58±5% and 35±5%, respectively). Cytogenetic risk classification and age were significant prognostic factors: the 2-year leukemia-free survival was 63±4% in patients with good risk cytogenetics, 52±3% in those with intermediate risk cytogenetics, and 37 ± 10% in those with poor risk cytogenetics (P=0.01); patients ≤50 years old had better overall survival (77±2% versus 56±3%; P<0.001), leukemia-free survival (61±3% versus 45±3%; P<0.001), relapse incidence (35±2% versus 45±3%; P<0.005), and non-relapse mortality (4±1% versus 10±2%; P<0.001) than older patients. The combination of intravenous busulfan and high-dose melphalan was associated with the best overall survival (75±4%). Our results suggest that the use of intravenous busulfan simplifies the autograft procedure and confirm the usefulness of autologous stem cell transplantation in acute myeloid leukemia. As in allogeneic transplantation, veno-occlusive disease is an uncommon complication after an autograft using intravenous busulfan.

Demora desde o aparecimento dos primeiros sintomas até ao diagnóstico da tuberculose pulmonar em Portugal : análise de sobrevivência

RESUMO - O presente estudo tem como objetivo contribuir para a Saúde Pública no controlo da tuberculose pulmonar (TBP), estudando a demora desde o aparecimento dos primeiros sintomas até ao diagnóstico da doença. As consequências da demora no diagnóstico podem ser fatais para os doentes e intensificar a proliferação do bacilo, influenciando a incidência da doença. Este estudo analisou os casos notificados com TBP pelo SVIG-TB, em Portugal Continental, no período de 2000 a 2009, com demora no diagnóstico de 1 a 365 dias. Foram utilizadas técnicas de estatística clássica para caracterização da base de dados e de análise de sobrevivência para caracterizar a demora até ao diagnóstico e modelar o risco de diagnóstico. As variáveis incluídas no estudo foram: género, idade, grupo etário, distrito de residência, área crítica de incidência da tuberculose, presença ou ausência da infeção pelo VIH, caso novo e reincidência, número de tratamentos anteriores, presença ou ausência de fatores de risco (álcool, tabaco, outras drogas, reclusão e sem-abrigo) e número de fatores de risco. Verificou-se que nos 35 711 casos notificados a mediana da demora até ao diagnóstico foi de 55 dias. Todas as variáveis referidas anteriormente demostraram estar correlacionadas com a demora, exceto no que diz respeito às áreas críticas ou não críticas e aos sem-abrigo. No modelo de Cox as variáveis que se mostraram relevantes ao diagnóstico foram o género em 10,2%, grupos etários, distritos, presença ou ausência de VIH em 12%, dependência alcoólica em 6,3% e dependência de tabaco em 8,8%. Estes resultados apontam para a efetividade de medidas de controlo da tuberculose, principalmente no caso de a pessoa apresentar alguns fatores de risco.

Nominal and inflation-linked government bonds: An assessment of arbitrage opportunities in UK Gilt Market

A Work Project, presented as part of the requirements for the Award of a Masters Degree in Finance from the NOVA – School of Business and Economics

Pig bite in Brazil: a case series from a teaching hospital

A retrospective survey done from 1987 till 1990 revealed that 23 patients bitten by pigs sought medical help at a teaching hospital in Uberlândia, in southeastern Brazil. Most cases (21) were from Uberlândia. The cases were evenly distributed by month and by year; most of them (14/16; 87.5%) occurred between 7. OOa.m. and 7.00 p. m. The male to female ratio was 6.7:1. Age ranged from 6 to 73 (mean 38.95 ± SD 22.06, median 36). The bites were more common on the upper limbs, particularly on the forearms. In 11(47.8%) cases the injury was described as deep. In most cases where information was available the injury was related to capture, transport or immobilisation ofthe pigfor slaughter. The following medical procedures were performed: local cleansing in 19(82.6%) cases, rabies vaccine (12; 52.2%), antirabies serum (2; 8.7%), suturing (6; 26.1%) and tetanus vaccine (12; 52.2%). There was no case of infection at the bite site, neither of rabies or tetanus. By our data, the annual incidence of pig bite in Uberlândia can be estimated to be about 1.5/100.000.

Effects of water deprivation on renal hydroelectrolytic excretion in chronically Trypanosoma cruzi-infected rats

The effect of an 8 hour-period of water deprivation on fluid and electrolyte renal excretion was investigated in male Wistar rats infected with the strain São Felipe (12SF) of Trypanosoma cruzi, in comparison with age and sex matched non-infected controls. The median percent reductions in the urinary flow (-40% v -63%) and excretion ofsodium (-57% v-79%) were smaller in chagasic than in control rats, respectively. So, chagasic rats excreted more than controls. On the other hand, the median percent decrement in the clearance of creatinine was higher in chagasic (-51%) than in controls (-39%). Thus, chagasic rats showed some disturbed renal hydroelectrolytic responses to water deprivation, expressed by smaller conservation, or higher excretion of water and sodium in association with smaller glomerularfiltration rate. This fact denoted an elevation in the fractional excretion of sodium and water.

Clinical and epidemiological findings during a measles outbreak occurring in a population with high vaccination coverage

From March 1991 to April 1992, 250 measles suspected cases were studied in the Municipality of Niterói, State of Rio de Janeiro. The median age found was 11 years and 76.0% of the cases were in school age children. Exposure histories were present in 149 patients and schools were the most frequent sites of transmission (45.0%). Vaccination status was known for 127 studied cases and 76.4% of them had received measles vaccine before their first birthday. One or more complications were reported for 68 cases aitd in 8.9% of the studied cases hospitalization was required. Frequency of complications varied according to each age group studied and were more commonly encountered among children < 1 year of age (55.6%). The history of previous vaccination did not diminish the number of complications of the cases studied. The results of this work show changes in age distribution of measles leading to sizeable outbreaks among teenagers and young adults.

Inefficient commuting in a city with spillovers

A Masters Thesis, presented as part of the requirements for the award of a Research Masters Degree in Economics from NOVA – School of Business and Economics

Longitudinal comparison between plasma and seminal HIV-1 viral loads during antiretroviral treatment

This study was designed to investigate the impact of anti-retroviral therapy on both plasma and seminal HIV-1 viral loads and the correlation between viral loads in these compartments after treatment. Viral load, CD4+ and CD8+ T-cell counts were evaluated in paired plasma and semen samples from 36 antiretroviral therapy-naïve patients at baseline and on days 45, 90, and 180 of treatment. Slopes for blood and seminal viral loads in all treated patients were similar (p = 0.21). Median HIV-1 RNA titers in plasma and semen at baseline were 4.95 log10 and 4.48 log10 copies/ml, respectively. After 180 days of therapy, the median viral load declined to 3.15 log10 copies/ml (plasma) and 3.2 log10 copies/ml (semen). At this timepoint 22 patients presented HIV-1 viral load below 400 copies/ml in either plasma or semen, but only 9 had viral loads below 400 copies/ml in both compartments.

Retrospective study of 151 patients with cutaneous leishmaniasis treated with meglumine antimoniate

We retrospectively analyzed a series of 151 cases of cutaneous leishmaniasis treated between 1967 and 1982. One-hundred-and-thirty-nine (92%) patients presented with active lesions and were treated with daily doses of meglumine antimoniate: 81 adults received a 5-ml vial IM and 58 children received 1 to 5ml. Forty-five (32.4%) patients underwent continuous treatment with meglumine antimoniate for 25 to 116 days without rest intervals, and 94 (67.6%) intermittent treatment with 2 to 5 series of meglumine antimoniate. Intermittent series could include schedules of daily IM applications for 10 to 25 days each and intervals varying from 10 to 60 days. Antimony dose was calculated for 66 (47.5%) patients and ranged from 3.9 to 28.7 Sb5+/kg/day. Of these, 35 patients received >10mg and 31 patients <10mg Sb5+/kg/day. Median time of healing was longer for lesions on the legs and feet - 67.5 days versus 48.7 days (p < 0.001) for other sites. However, there were no significant differences in the median time of healing between adults and children, intermittent and continuous regimens or high and low antimony doses. Fifty-one patients were reassessed 5 to 14 years after treatment and showed no evidence of disease. These results support further investigation (clinical trials) on treatment using low doses of antimony.

An alternative antimonial schedule to be used in cutaneous leishmaniasis when high doses of antimony are undesirable

Despite more than half a century of use in leishmaniasis, antimony therapy still presents serious problems concerning dosage and toxicity. Low and high doses have been shown to be equally effective. In this paper, the feasibility of injecting one ampoule of meglumine antimoniate intramuscularly every other day until clinical cure is demonstrated, while studying a series of 40 cutaneous leishmaniasis cases. Total dose used varied from 1,822.5 to 12,150mg of pentavalent antimony and total time of treatment varied from 3 to 10 weeks, with 86% efficacy. Thirty-six out of the 40 patients are still on follow-up with a mean time of 10.7 ± 7 months and a median of 9 months. No relapse or mucosal lesions have been noted so far. The schedule showed good tolerance and easy application and its efficacy was comparable to the officially recommended WHO schedule. Therefore, such a schedule represents a valuable alternative for the cases with high toxicicity to antimony or daily injections are an obstacle to the treatment.

Intestinal helminthes and/or Toxocara infection are unrelated to anti-HBs titers in seven-year-old children vaccinated at birth with recombinant hepatitis B vaccine

The aim of this investigation was to evaluate the possible effect of nematode infection on anti-HBs antibody levels in the serum of seven-year-old schoolchildren vaccinated at birth with the recombinant hepatitis B vaccine. Anti-HBs and anti HBc antibodies were evaluated in the sera of 100 schoolchildren with at least one intestinal nematode and/or a positive serological reaction for anti-Toxocara antibodies and in 95 schoolchildren without intestinal helminthiasis or serum anti-Toxocara antibodies. Both groups were from public elementary schools located on the urban periphery of Vitória, ES, Brazil. Among these 195 children, the median anti-HBs antibody titer was 31.3IU/ml and the frequency of titers less than 10IU/ml was 33.8% (95% CI: 27.1-40.4%). There were no significant differences between the medians of anti-HBs titers or the frequency of titers less than 10IU/ml between the groups with or without helminthes (29.5 and 32.9IU/ml and 33 and 34.7%, respectively; p>0.05). Even when the children with intestinal nematodes and/or anti-Toxocara antibodies and with blood eosinophil counts over 600/mm³ were compared with children without infection from intestinal nematodes and without anti-Toxocara antibodies, with blood eosinophil counts less than 400 eosinophils/mm³, these differences were not significant. None of the children presented anti-HBc antibodies. In conclusion, infections with intestinal nematodes and/or the presence of anti-Toxocara antibodies did not interfere with the anti-HBs antibody titers in seven-year-old children vaccinated at birth with the recombinant hepatitis B vaccine.

Development of composite particles for pulmonary delivery

In this work, biocompatible and biodegradable poly(D-L-lactide-co-glycolide) (PLGA) microparticles with the potential for use as a controlled release system of vaccines and other drugs to the lung were manufactured using supercritical CO2, through the Supercritical Assisted Atomization (SAA) technique. After performing a controlled variance in production parameters (temperature, pressure, CO2/solution flow ratio) PLGA microparticles were characterized and later used to encapsulate active pharmaceutical ingredients (API). Bovine serum albumin (BSA) was chosen as model protein and vaccine, while sildenafil was the chosen drug to treat pulmonary artery hypertension and their effect on the particles characteristics was evaluated. All the produced formulations were characterized in relation to their morphology (Morphologi G3 and scanning electronic microscopy (SEM)), to their physical-chemical properties (X-ray diffraction (XRD, differential scanning calorimetry (DSC), Fourier transform infrared (FTIR)) and aerodynamic performance using an in vitro aerosolization study – Andersen cascade impactor (ACI) - to obtain data such as the fine particle fraction (FPF) and the mass median aerodynamic diameter (MMAD). Furthermore, pharmacokinetic, biodegradability and biocompatibility tests were performed in order to verify the particle suitability for inhalation. The resulting particles showed aerodynamic diameters between the 3 and 5 μm, yields up to 58% and FPF percentages rounding the 30%. Taken as a whole, the produced microparticles do present the necessary requests to make them appropriate for pulmonary delivery.

Clinical and radiographic features of HIV-related pulmonary tuberculosis according to the level of immunosuppression

Medical charts and radiographs from 38 HIV-infected patients with positive cultures for Mycobacterium tuberculosis from sputum or bronchoalveolar lavage were reviewed in order to compare the clinical, radiographic, and sputum bacilloscopy characteristics of HIV-infected patients with pulmonary tuberculosis according to CD4+ lymphocyte count (CD4). The mean age of the patients was 32 years and 76% were male. The median CD4 was 106 cells/mm³ and 71% had CD4 < 200 cells/mm³. Sputum bacilloscopy was positive in 45% of the patients. Patients with CD4 < 200 cells/mm³ showed significantly less post-primary pattern (7% vs. 63%; p = 0.02) and more frequently reported weight loss (p = 0.04). Although not statistically significant, patients with lower CD4 showed lower positivity of sputum bacilloscopy (37% vs. 64%; p = 0.18). HIV-infected patients with culture-confirmed pulmonary tuberculosis had a high proportion of non-post-primary pattern in thoracic radiographs. Patients with CD4 lower than 200 cells/mm³ showed post-primary patterns less frequently and reported weight loss more frequently.

Chagas' disease and ageing: the coexistence of other chronic diseases with Chagas' disease in elderly patients

This study aimed to identify the main comorbidities in elderly chagasic patients treated in a reference service and identify possible associations between the clinical form of Chagas' disease and chronic diseases. Ninety patients aged 60 years-old or over were interviewed and their clinical diagnoses recorded. The study population profile was: women (55.6%); median age (67 years); married (51.1%); retired (73.3%); up to four years' education (64.4%); and earning less than two minimum wages (67.8%). The predominant forms of Chagas' disease were the cardiac (46.7%) and mixed forms (30%). There was a greater proportion of mild cardiac dysfunction (84.1%), frequently in association with megaesophagus. The mean number of concurrent diseases was 2.856 ± 1.845, and 33% of the patients had four or more comorbidities. The most frequent were systemic arterial hypertension (56.7%), osteoporosis (23.3%), osteoarthritis (21.2%) and dyslipidemia (20%). Positive correlations were verified between sex and comorbidities and between age group and comorbidities.

Metodologias de tratamento em microfilmes de acetato de celulose

A presente dissertação, integra-se no projeto ‘Digitalização e Tratamento da Filmoteca Ultramarina Portuguesa’, que inclui o tratamento e digitalização de uma coleção de microfilmes em películas de 35 mm em AC. A coleção é composta por mais de meio milhão de exposições (511.397) de variadas marcas comerciais. Deste conjunto, os negativos da marca Perutz são a parte considerada em pior estado de preservação, contendo itens considerados irrecuperáveis, devido ao seu total encurvamento e enrolamento, comportamento incomum relacionado com a deterioração do AC. Portanto, este conjunto constitui o nosso objeto de estudo, prioritário a recuperar a informação contida nestes microfilmes, pois as coleções originais, em papel, estão inacessíveis e em mau estado de conservação. Devido a uma deterioração atípica, uma das etapas principais é compreender o material, tendo-se recorrido à MO, para análise da estratigrafia, à μ-FTIR e à medição da acidez com as A-D STRIPS® e dois métodos de potenciometria de pH (com a utilização de dois tipos de elétrodo, superfície plana e microelétrodo). Nos microfilmes aparentemente impossíveis de desenrolar, foram ensaiados e comparados neste estudo, diferentes tratamentos de C&R tradicionalmente aplicados nesta área, designadamente humidificação e transferência de emulsão, os quais se revelaram inadequados para as deteriorações em presença. Foi assim necessário recorrer a outras áreas afins da fotografia, para poder encontrar uma solução já testada com sucesso, a qual estaria na área do cinema, com o tratamento deshrinking que permitiu a recuperação da imagem possibilitando a sua informatização e colocação em base de dados, com o benefício inesperado de uma planificação permanente do objeto. Recorreu-se também à área da digitalização 3D e modulação computacional, mas sem resultados até a data. Assim, o tratamento deshrinking mostrou-se o mais eficaz sendo aprimorado, tendo-se passado de uma simples ação pontual e reversível de planificação para uma mais definitiva.