176 resultados para dose finding


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Response to treatment with antimonial drugs varies considerably depending on the parasite strain involved, immune status of the patient and clinical form of the disease. Therapeutic regimens with this first line drug have been frequently modified both, in dose and duration of therapy. A regimen of 20 mg/kg/day of pentavalent antimony (Sb5+) during four weeks without an upper limit on the daily dose is currently recommended for mucosal disease ("espundia"). Side-effects with this dose are more marked in elderly patients, more commonly affected by this form of leishmaniasis. According to our experience, leishmaniasis in Rio de Janeiro responds well to antimony and, in cutaneous disease, high cure rates are obtained with 5 mg/kg/day of Sb5+ during 30 to 45-days. In this study a high rate of cure (91.4%) employing this dose was achieved in 36 patients with mild disease in this same geographic region. Side-effects were reduced and no antimony refractoriness was noted with subsequent use of larger dose in patients that failed to respond to initial schedule.

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The clinical significance of isolated anti-HBc is still a challenge. To elucidate the real importance of this finding in our blood donors, an investigation algorithm was tested. One hundred and twelve isolated anti-HBc seropositive blood donors underwent clinical evaluation and retesting of HBV markers. Those who presented repeatedly reactive isolated anti-HBc, received a single dose of hepatitis B recombinant vaccine to verify anti-HBs early response. A HBV-DNA determination by PCR was done for those who did not test positive to anti-HBs after vaccine. The level of anti-HBc was recorded as a ratio of the sample-to-cut-off values (S:C ratio) in 57 candidates at donation. Comparing true and false-positive anti-HBc results, the different S:C ratios of them were statistically significant and when less than 2, implying in a false-positive result probability over 80%. A high percent of false-positive results (16.07%) was verified after anti-HBc retesting. HBV immunity was characterized in 49.11%, either by anti-HBs detection in retesting (15.18%), or after a single dose HBV vaccination (33.93%). HBV-DNA was negative in all tested donors. In conclusion, this algorithm was useful to clarify the meaning of isolated anti-HBc in most of our blood donors.

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The aim of this article is to present an investigation of cure rate, after long follow up, of specific chemotherapy with benznidazole in patients with both acute and chronic Chagas disease, applying quantitative conventional serological tests as the base of the criterion of cure. Twenty one patients with the acute form and 113 with one or other of the various chronic clinical forms of the disease were evaluated, after a follow up period of 13 to 21 years, for the acute, and 6 to 18 years, for the chronic patients. The duration of the acute as well as the chronic disease, a condition which influences the results of the treatment, was determined. The therapeutic schedule was presented, with emphasis on the correlation between adverse reactions and the total dose of 18 grams, approximately, as well as taking into consideration precautions to assure the safety of the treatment. Quantitative serological reactions consisting of complement fixation, indirect immunofluorescence, indirect hemagglutination, and, occasionally, ELISA, were used. Cure was found in 76 per cent of the acute patients but only in 8 per cent of those with chronic forms of the disease. In the light of such contrasting results, fundamentals of the etiological therapy of Chagas disease were discussed, like the criterion of cure, the pathogenesis and the role of immunosuppression showing tissue parasitism in long standing chronic disease, in support of the concept that post-therapeutic consistently positive serological reactions mean the presence of the parasite in the patient's tissues. In relation to the life-cycle of T. cruzi in vertebrate host, there are still some obscure and controversial points, though there is no proof of the existence of resistant or latent forms. However, the finding over the last 15 years, that immunosuppression brings about the reappearance of acute disease in long stand chronic patients justifies a revision of the matter. Facts were quoted in favor of the treatment of chronic patients.

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Malaria regions of the Amazon basin have been characterized by difficult access and non-compliance of the patients to treatment. In an attempt to assess the schizonticide efficacy of chloroquine in a single dose of 600 mg, the authors realized a double-blind, placebo-controlled trial in 132 outpatients with vivax malaria. Patients were distributed into two groups: group CPLA, given chloroquine 600 mg (single dose) on the first day of treatment, and two doses of placebo on second and third days. Group CHLO, given chloroquine 600 mg on first day and 450 mg on second and third day. Geometric means of the parasite density during the follow-up was similar in both groups. No differences were observed in the parasitological cure between the two groups (p = 0.442). There was clinical and parasitological efficacy in treatment of patients given a single-dose of chloroquine. This suggests that its restricted use could be indicated in remote areas of Brazilian Amazon Region, nevertheless the inadequate response of three patients indicates the need for further studies.

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Paracoccidioidomycosis (PCM) is caused by the dimorphic fungus Paracoccidioides brasiliensis (Pb) and corresponds to prevalent systemic mycosis in Latin America. The aim of the present work was to evaluate the dose response effect of the fungal yeast phase for the standardization of an experimental model of septic arthritis. The experiments were performed with groups of 14 rats that received doses of 103, 104 or 105 P. brasiliensis (Pb18) cells. The fungi were injected in 50 µL of phosphate-buffered saline (PBS) directly into the knee joints of the animals. The following parameters were analyzed in this work: the formation of swelling in knees infused with yeast cells and the radiological and anatomopathological alterations, besides antibody titer by ELISA. After 15 days of infection, signs of inflammation were evident. At 45 days, some features of damage and necrosis were observed in the articular cartilage. The systemic dissemination of the fungus was observed in 11% of the inoculated animals, and it was concluded that the experimental model is able to mimic articular PCM in humans and that the dose of 105 yeast cells can be used as standard in this model.

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Os autores medicaram 50 pacientes portadores de ascaríase com o Hidrato de Piperazina a 20% na dose única de 0,5 ml por Kg de pêso, sem exceder 6,0 g. Conseguiram cura radical em 76% dos casos e redução de 98% no eliminação dos ovos pelas fezes. A tolerância ao produto foi excelente e recomendam o mesmo para o tratamento da referida helmintiase.

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Os autores apresentam estudo de 90 pacientes medicados pelo Pamoato de Pirantel (Trans-1,4,5,6-Tetraidro-1-metil-1-2/2- (2-Tienil) vinil/pirimidina). todos portadores de parasitoses intestinais, principalmente Ascaris lumbricoides e Enterobius vermicularis. Os pacientes foram divididos em dois grupos; o primeiro, constituído de 25 pacientes, recebeu a dosagem de 5mg/kg, dose única, numa só tomada e neste grupo apenas se estudou a atividade terapêutica na ascaridiase e enterobiase. No segundo grupo, de 65 pacientes, empregou-se a dose única de 10mg/kg numa só tomada e foi estudada, além da ação terapêutica na ascaridiase e enterobiase, possível atividade também sôbre outras helmintiases. Todos os pacientes após a medicação eram submetidos a 3 exames proctoparasitoscópicos de controle (no 7º, 15º, e 30º dia) e nos casos prèviamente positivos para Enterobius vermicularis também se fêz controle no 7º e 15º dia pelo "Anal-swab". Comprovaram os autores no primeiro grupo, cura proctoparasitológica de 13 dos 18 casos de ascaridiase (72,2%); na enterobiase obtiveram cura de 61,5%, e na associação Ascaris-Enterobius obtiveram cura de 50,0% de ambos os parasitas, não havendo, entretanto, nenhum caso de falha total nos casos restantes. No segundo grupo, os resultados que obtiveram foram os seguintes: ascaridiase, 50 casos; curados, 40 (80,0%). Enterobiase, 22 casos; curados, 16 (72,7%). Necaturiase, 8 casos; curados, 5 (17,8%). Tricuríase, 41 casos; curados, 5 (12,1%). Estrongiloidiase, 5 casos; curado, 1 caso (20,0%). Associação Enterobius-Ascaris, 14 casos; cura total de ambos os parasitas em 10 casos (71,4%); 4 casos com cura parcial de um ou do outro parasita, não havendo falha total em nenhum caso. Empregaram comprimidos contendo 100 e 300mg da substância ativa, e forma liquida contendo 10mg da substância ativa por cm³. Efeitos colaterais reduzidos em número e em intensidade; o primeiro grupo 12,0% dos casos (epigastralgia, tonturas e diarréia); no segundo grupo 23,07% dos casos (predominando epigastralgia, tonturas, cefaléia, dôres abdominais difusas e diarréia). Os autores concluem indicando ser o Pamoato de Pirantel droga muito eficaz no tratamento da ascaridiase e enterobiase, inclusive na associação destas duas parasitoses. A droga apresenta efeitos colaterais discretos e é de fácil ministração (pequeno número de comprimidos, dose única e forma líquida de sabor muito agradável). Indicam como eleita a dosagem de 10mg/kg, que sem alterar significativamente a intensidade e incidência dos efeitos colaterais, apresenta maior atividade terapêutica na ascaridiase, enterobiase e na associação dessas duas parasitoses.

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A oxamniquine em cápsulas foi usada no tratamento de 132 doentes com esquistossomose mansoni crônica, sendo 129 com a forma hepato-intestinal e 3 com a forma hepato-esplênica. A dose foi de 10 mg por quilo de peso corporal em 34 pacientes, 12.5 mg em 35 e 15 mg em 63. A tolerância foi excelente em 43,2% dos tratados, boa em 48,5% e satisfatória em 8,3%. As queixas mais freqüentes foram tonturas e sonolência, que aparecem logo após a ingestão da droga e são fugazes. Os exames de laboratório mostraram em um ou outro paciente somente discreta retenção de bromosulfaleina, aumento de transaminase e da bilirrubina, insuficientes para caracterizar uma hepatoxicidade evidente. O seguimento dos pacientes se prolongou por mais de quatro meses e constou de pelo menos cinco exames de fezes pelo método de sedimentação. Todos os exames foram negativos em 20 (66,66%) pacientes que tomaram 10 mg, em 13 (56,52%) que tomaram 12.5 mg e em 41 (89,13%) que tomaram 15 mg. Excluindo-se os menores de 16 anos subiu a 95% a negatividade entre os que foram tratados com 15 mg.

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Os autores trataram 30 pacientes portadores de colite amebiana não disentérica, de ambos os sexos (17 homens e 13 mulheres), com idades compreendidas entre 15 (dois casos) a 55 anos (um doente), na Disciplina de Doenças Infecciosas. Parasitárias da Universidade Federal de Pernambuco. A posologia administrada foi de 1.500 mg em dose única e os resultados avaliados pelas técnicas de Hoffman, raspado da mucosa retaí, retossigmoidoscopia (em 16 enfermos) e exame direto com ou sem coloração pelo lugol, foram de 80% (24 doentes) de cura clínica e laboratorial. Nenhuma manifestação colateral foi relatada petos pacientas e concluem os autores que o Teclozan administrado em nova posologia, representa valioso subsídio no tratamento da amebíase intestinal.

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Foi avaliada a função renal de 11 pacientes com leishmaniose cutâneo-mucosa tratados com antimonial pentavalente na dose de 40mg SbV/kg/dia aplicada de 12/12 horas, em esquema contínuo, durante trinta dias. No estudo, um paciente apresentou insuficiência renal reversível e dois desenvolveram alterações enzimáticas hepáticas e eletrocardiográficas sendo o esquema terapêutico interrompido. Nos demais pacientes observou-se efeitos nefrotóxicos tais como diminuição da taxa de filtração glomerular, diminuição da capacidade de concentração urinária, avaliada por um jejum hídrico de 16 horas e aumento na fração de excreção de sódio. No exame do sedimento urinário observou-se um aumento no número de leucócitos e cilindros. Os resultados encontrados neste estudo sugerem que o tratamento com antimonial pentavalente na dose de 40mg SbV/kg/dia foi menos tolerado em virtude de seus efeitos tóxicos, não parecendo apresentar índice de cura superior ao esquema atualmente preconizado de 20mg SbV/kg/dia.

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Os autores relatam um caso de leishmaniose cutâneo-mucosa em uma paciente de 89 anos, diabética e hipertensa, tratada inicialmente com alopurinol por 10 meses não havendo cicatrização das lesões. Posteriormente, recebeu antimoniato de N-metil glucamina (glucantime) por 4 dias, na dose total de 2.380mg do Sb v, mas desenvolveu cardiotoxicidade e hipocalemia, sendo suspenso o tratamento, entretanto, evoluiu com regressão clínica total das lesões, apesar de ter recebido pequena dose desta medicação.

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Humoral immune response using inactivated rabies vaccine was studied in 35 nelore cross-bred bovines of western region of São Paulo state. Ninety days after vaccination, 13 (92.8%) animals presented titers 30.5IU/ml, through mouse neutralization test. After 180 days, 9 (64.3%) sera showed titers 30.5IU/ml, after 270 days, only one (7.1%) showed a titer of 0.51IU/ml, and after 360 days, all animals showed titers < 0.5IU/ml. Group of animals receiving booster dose 30 days after vaccination presented, two months after, all with titers > 0.5IU/ml. At 180 days, 17 (80.9%) sera presented titers > 0.5IU/ml; at 270 days, 15 (71.4%), with titers 30.5IU/ml and at 360 days, 4 (19.0%), with titers 30.5IU/ml. Booster-dose ensured high levels of neutralizing antibodies for at least three months, and 240 days after revaccination, 71.4% of animals were found with titers 30.5IU/ml.

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In August/1999, a group of 14 adults from the staff of a private hospital in Contagem -- Minas Gerais State, Brazil, received unintentionally a 25 times concentrated dose of the 17-DD yellow fever vaccine (Bio-Manguinhos), due to a mistake at the reconstitution step. All patients were clinically and laboratorially evaluated at days 5, 13 and 35 post vaccination. Frequency of side effects and clinical observations of this group of individuals were not different from the observed in recipients immunized with normal doses of the vaccine. At the second and third evaluation none of the subjects reported symptoms. None of the patients presented abnormalities at the physical examination at none of the time points and in all cases the blood examination was normal, except for a reduced number of platelets that was detected in one subject at the first and second evaluation and reverted to normal at third evaluation. At the first evaluation point, 8 subjects were serum negative and 6 serum positive for yellow fever at the plaque reduction neutralization test. In 5 subjects the observed titre was 10 times higher as the baseline of 2.36 Log10 mUI/ml. The samples collected at second and third evaluation (13th and 35th days) demonstrated that all subjects responded to the vaccination with the exception of one that did not present a positive result in any of the samples collected. This evaluation confirms the safety of the 17-DD yellow fever vaccine.