Splenectomy in a patient with treatment-resistant visceral leishmaniasis: a case report

Visceral leishmaniasis (VL), also known as Kala-azar, is a systemic infection caused by a protozoan (Leishmania) and, in its classic form, is a serious illness associated with malnutrition, anemia, hepatosplenomegaly, infectious processes and coagulopathies. The effect of splenectomy in patients with visceral leishmaniasis is not well defined; however, it is known that the spleen is the largest reservoir of infected cells belonging to the reticulo endothelial system. Therefore, the surgical procedure is an option for the debulking of parasites, providing a cure for refractory VL and minimizing the complications of hypersplenism.

Electroconvulsive therapy in treatment-resistant mania: case reports

Electroconvulsive therapy is known to be effective in the treatment of mood disorders, more specifically for depression and mania. Although a large body of evidence confirms the efficacy of electroconvulsive therapy in the treatment of mania, few prospective studies have been done to assess its effectiveness in treatment-resistant manic episodes. These case reports describe the initial results of a study that is being conducted to evaluate the efficacy of Electroconvulsive therapy among treatment-resistant bipolar patients. METHODS: Three manic patients (according to DSM-IV criteria) who were considered treatment-resistant underwent a series of 12 bilateral Electroconvulsive therapy sessions. Before the treatment and then weekly, they were evaluated with the following rating scales: Young Mania Rating Scale, Hamilton Rating Scale for Depression, Brief Psychiatric Rating Scale, and Clinical Global Impressions-Bipolar Version. RESULTS: The 3 patients showed a satisfactory response to Electroconvulsive therapy, although some differences in the course of response were observed. CONCLUSION: These case reports suggest that Electroconvulsive therapy needs further evaluation for the treatment of resistant bipolar patients.

Bilateral repetitive transcranial magnetic stimulation for treatment-resistant depression: a systematic review and meta-analysis of randomized controlled trials

There has been concern regarding the use of controversial paradigms for repetitive transcranial magnetic stimulation (rTMS) to manage treatment-resistant depression (TRD). This meta-analysis assessed the efficacy of bilateral rTMS compared with unilateral and sham rTMS in patients with TRD. PubMed, Embase, CENTRAL, PsycINFO, Web of Science, EAGLE and NTIS databases were searched to identify relevant studies, and randomized controlled trials (RCTs) on bilateral rTMS for TRD patients were included. The response was defined as the primary outcome, and remission was the secondary outcome. Ten RCTs that included 634 patients met the eligibility criteria. The risk ratio (RRs) of both the primary and secondary outcomes of bilateral rTMS showed non-significant increases compared to unilateral rTMS (RR=1.01, P=0.93; odds ratio [OR]=0.77, P=0.22). Notably, the RR of the primary bilateral rTMS outcome was significantly increased compared to that for sham rTMS (RR=3.43, P=0.0004). The results of our analysis demonstrated that bilateral rTMS was significantly more effective than sham rTMS but not unilateral rTMS in patients with TRD. Thus, bilateral rTMS may not be a useful paradigm for patients with TRD.

Depressão resistente a tratamento: uma revisão das estratégias farmacológicas de potencialização de antidepressivos

OBJETIVO: Fazer uma revisão sobre oito estratégias farmacológicas de potencialização de antidepressivos na DRT. MÉTODOS: Fez-se um levantamento bibliográfico de 1990 até janeiro de 2006, nas bases eletrônicas de busca Medline, LILACS e da Biblioteca Cochrane, utilizando-se os termos de busca treatment, resistant, refractory e depression e os descritores depression, drug resistance e augmentation, incluindo apenas ensaios controlados duplo-cegos. Foi consultada a referência dos artigos para obtenção de ensaios realizados em data anterior a 1990 e artigos originais de valor histórico. RESULTADOS: Foram encontrados 17 estudos duplo-cegos com o lítio, seis com o hormônio tireoidiano, dois com a buspirona, seis com o pindolol, um com a carbamazepina, dois com a lamotrigina e quatro com a olanzapina. Foram favoráveis à potencialização 41,2% dos ensaios com lítio; 60% daqueles com hormônio tireoidiano e antidepressivos tricíclicos e nenhum com hormônio tireoidiano e inibidores seletivos da recaptação da serotonina (ISRS); 50% dos com pindolol; 100% dos ensaios com carbamazepina e 40% daqueles com olanzapina. Nenhum dos estudos com a buspirona foi favorável. No único estudo com lamotrigina não houve eficácia de tratamento na avaliação pelo critério principal, mas superioridade ao placebo em critérios secundários. CONCLUSÃO: Na DRT há evidência de eficácia apenas em relação ao lítio na potencialização de várias classes de antidepressivos e ao hormônio tireoidiano na potencialização de tricíclicos. A olanzapina foi razoavelmente estudada e sua eficácia não foi estabelecida. Os poucos estudos realizados com a buspirona e o pindolol não comprovaram sua eficácia. A carbamazepina foi muito pouco estudada, e a lamotrigina ainda não foi adequadamente avaliada.

Modificação enzimática da farinha de arroz visando a produção de amido resistente

The aim of this work was to study the enzymatic modification on rice flour using lipase pancreatic and amyloglucosidase to obtain resistant starch. For this, Response Surface Methodology (RSM) was used to determine the best operating conditions for each enzyme. For lypase pancreatic, the highest value for resistant starch (45%) was achieved within 2 h reaction at pH 7 using an enzyme/substrate ratio of 4% (w/w) and Dp= 100/200 tyler. For amyloglucosidase, optima conditions corresponded to an enzyme/substrate ratio of 0,006 mL/g and Dp= 100/200 tyler at 45 ºC, yielding 57% of resistant starch in 2 h reaction. These results show the potential of using both enzymes to modified rice flour, increasing the resistant starch in about 5.7 folds in relation to the flour without treatment (resistant starch=10.6%).

Omeprazole, Furazolidone, and Tetracycline: an eradication treatment for resistant H. pylori in Brazilian patients with peptic ulcer disease

OBJECTIVES: To determine the efficacy of a simple, short-term and low-cost eradication treatment for Helicobacter pylori (H. pylori) using omeprazole, tetracycline, and furazolidone in a Brazilian peptic ulcer population, divided into 2 subgroups: untreated and previously treated for the infection. PATIENTS AND METHODS: Patients with peptic ulcer disease diagnosed by endoscopic examination and infected by H. pylori diagnosed by the rapid urease test (RUT) and histological examination, untreated and previously unsuccessfully treated by macrolides and nitroimidazole, were medicated with omeprazole 20 mg daily dose and tetracycline 500 mg and furazolidone 200 mg given 3 times a day for 7 days. Another endoscopy or a breath test was performed 12 weeks after the end of treatment. Patients were considered cured of the infection if a RUT and histologic examination proved negative or a breath test was negative for the bacterium. RESULTS: Sixty-four patients were included in the study. The women were the predominant sex (58%); the mean age was 46 years. Thirty-three percent of the patients were tobacco users, and duodenal ulcer was identified in 80% of patients. For the 59 patients that underwent follow-up examinations, eradication was verified in 44 (75%). The eradication rate for the intention-to-treat group was 69%. The incidence of severe adverse effects was 15%. CONCLUSION: The treatment provides good efficacy for H. pylori eradication in patients who were previously treated without success, but it causes severe adverse effects that prevented adequate use of the medications in 15% of the patients.

Chloroquine resistant Plasmodium falciparum malaria in Osogbo Nigeria: efficacy of amodiaquine + sulfadoxine-pyrimethamine and chloroquine + chlorpheniramine for treatment

Chloroquine (CQ) resistance in Plasmodium falciparum contributes to increasing malaria-attributable morbidity and mortality in Sub-Saharan Africa. Despite a change in drug policy, continued prescription of CQ did not abate. Therefore the therapeutic efficacy of CQ in uncomplicated falciparum malaria patients was assessed in a standard 28-day protocol in 116 children aged between six and 120 months in Osogbo, Southwest Nigeria. Parasitological and clinical assessments of response to treatment showed that 72 (62.1%) of the patients were cured and 44 (37.9%) failed the CQ treatment. High initial parasite density and young age were independent predictors for early treatment failure. Out of the 44 patients that failed CQ, 24 received amodiaquine + sulphadoxine/pyrimethamine (AQ+SP) and 20 received chlorpheniramine + chloroquine (CH+CQ) combinations. Mean fever clearance time in those treated with AQ+SP was not significantly different from those treated with CH+CQ (p = 0.05). There was no significant difference in the mean parasite density of the two groups. The cure rate for AQ+SP group was 92% while those of CH+CQ was 85%. There was a significant difference in parasite clearance time (p = 0.01) between the two groups. The 38% treatment failure for CQ reported in this study is higher than the 10% recommended by World Health Organization in other to effect change in antimalarial treatment policy. Hence we conclude that CQ can no more be solely relied upon for the treatment of falciparum malaria in Osogbo, Nigeria. AQ+SP and CH+CQ are effective in the treatment of acute uncomplicated malaria and may be considered as useful alternative drugs in the absence of artemisinin-based combination therapies.

Survey on the clinical trial results achieved in Brazil comparing praziquantel and oxamniquine in the treatment of mansoni schistosomiasis

A random, double-blind, parallel group clinical trial program was carried out to compare praziquantel, a recently developed anti-helmintic drug, and oxamniquine, an already established agent for treating mansoni schistosomiasis. Both drugs were administered orally as a single dose, on the average, praziquantel 55 mg/kg and oxamniquine 16 mg/kg BWT. The diagnosis and the parasitological follow-up lasting for a minimum of six months, were based on stool examinations according to Kato/Katz technique. A patient was considered cured if all results were negative and if he had performed at least three post-treatment controls, each one comprising three stool examinations. The finding of a single S. mansoni egg in any stool examination indicated, a therapeutical failure. A total of 267, cases were treated with praziquantel and 272 with oxamniquine. The two groups were homogeneous in regard to patients, age, clinical form of the disease, risk of reinfection and worm burden, relevant factors in the therapeutical response. The incidence and severity of untoward, effects were similar in both groups but abdominal distress and diarrhoea were more frequently reported under praziquantel and dizzines under oxamniquine (p < 0.05). In the former group a marked urticariform reaction was observed whereas in the latter one patient presented convulsion. The laboratory work-up. failed to disclose any significant alteration although the AST, ALT and y-GT mean values revealed a tendence to increase on the 7th day after oxamniquine intake. The overall parasitological cure rates were 75.5% (139/ 184) with praziquantel and 69.8% (134/192) with oxamniquine (p > 0.05). Amongst the noncured aptients a reduction of 88.6% and 74.6% in the mean number of eggs/g of feces Was seen following the treatment with praziquantel and oxamniquine, respectively (p < 0.05). In conclusion, in spite of their different chemical, pharmacological and toxicological profiles as well as mechanisms-of-action, inclusively praziquantel already had proved to be 100% active against S. mansoni strains resistant to oxamniquine, both drugs showed comparable tolerance and therapeutical efficacy.

Long term evaluation of etiological treatment of Chagas disease with benznidazole

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.

Study of antiretroviral mutants in HIV patients with treatment failures and the effect of risk factors in the virological failures

INTRODUCTION: Information about HIV phenotypes of resistant to available ART and the influence of different risk factors on virological failures (VF) in Costa Rican HIV positive patients prior or during HAART is unknown. MATERIALS AND METHODS: Eighty nine samples, 72 VF and 17 basal (before treatment) were analyzed by examining resistant mutants in reverse transcriptase (RT) and protease (PT) regions using Trugene or LIPA genotyping kits. Sixty eight control patients were selected and relevant information was collected in a questionnaire. RESULTS: Poor adherence, presence of resistant mutations and number of treatment's changes were the only significant factors found (p = 0.006, 0.04 and 0.01 respectively). From 66 sequenced samples, 78%, 50% and 50% showed resistance to NRTI (nucleoside reverse transcriptase inhibitors), NNRT (non-nucleoside reverse transcriptase inhibitors) and PI (protease inhibitors), respectively. The most frequent mutations were M41L, M184V, and T215FY in RT and L62PI, L10FIRV and M36I in PT. DISCUSSION: The most important factor related to treatment response in this study was adherence to treatment. Mutations in RT were related to the treatment failure while the ones found in PT were secondary mutations which have been previously described to influence the selection of primary resistance mutations in these regions. The study reveals the urgency to detect resistant mutations in VF to be considered by physicians for selection of treatment schedule, to analyze basal HIV patients for monitoring of the spread of resistant mutations and the importance to reinforce the adherence in the patients for overall treatment outcome.

Glucantime resistant Leishmania promastigotes are sensitive to pentostam

Growth inhibition in vitro tests were used to study the susceptibility to pentostam of different Leishmania strains involved in cutaneous and mucocutaneos leishmaniasis - one glucantime sensitive strain, three naturally glucantime resistant strains and one glucantime resistant line developed by in vitro drug exposure. Contrasting with the high degree , of glucantime resistance, all strains were sensitive to pentostam. These differences suggest that there is some relationship between chemical structure and in vitro activity for these antimonial compounds. These data justify a clinical re-evaluation to compare therapeutic efficacy of glucantime and pentostam in the treatment of leishmaniasis.

Trypanosoma cruzi: susceptibility to chemotherapy with benznidazole of clones isolated from the highly resistant Colombian strain

The present investigation was performed to evaluate the susceptibility of seven clones isolated from the highly resistant Colombian strains, prototype of Biodeme Type III. Seven clones previously obtained, showed a phenotypic homogeneity and high similarity with the parental strain. Eight groups of 30 mice were inoculated with one of seven clones or the parental strain; 20 were treated with benznidazole (100mg/kg/day) and 10 were untreated controls. Cure evaluations were done by parasitological and serological tests and PCR. Cure rates varied from 0% (null) to 16.7%. Correlation between positivity of parasitological and serological tests with positive PCR reached 37%. The results demonstrated the high resistance of the clones, suggesting the predominance of a highly resistant principal clone in this strain. The findings apparently indicate that the possibility of cure is minimal for patients infected with this biodeme; a fact that could affect the control of Chagas' disease through treatment of chronically infected people.