The use of glucan as immunostimulant in the treatment of a severe case of chromoblastomycosis

We report the case of an alternative treatment for a patient with a severe form of chromoblastomycosis that responded poorly to the traditional antifungal therapy. We hereby show, in this study, the improvement of lesions after treatment with itraconazole associated with an intramuscular administration of glucan. We observed that the regression of lesions was associated with an improvement of the cellular immune response. This favourable response that we observed suggests that the therapeutic regimen we used might be an option for the treatment of patients with a severe form of chromoblastomycosis.

Midterm and long-term results of percutaneous endovascular treatment of venous outflow obstruction after pediatric liver transplantation

PURPOSE: To evaluate retrospectively the midterm and long-term results of percutaneous endovascular treatment of venous outflow obstruction after pediatric liver transplantation. MATERIALS AND METHODS: During a 9-year period, 18 children with obstruction of a hepatic vein (HV) or inferior vena cava (IVC) anastomosis underwent percutaneous transluminal angioplasty (PTA) with balloon dilation or stent placement in case of PTA failure after liver transplantation. Patients` body weights ranged from 7.7 kg to 42.6 kg (mean, 18.8 kg +/- 9). Potential predictors of patency were compared between balloon dilation and stent placement groups. RESULTS: Forty-two procedures were performed (range, 1-11 per patient; mean, 2). Technical and initial clinical success were achieved in all cases. Major complications included one case of pulmonary artery stent embolization and one case of hemothorax. Three children (25%) with HV obstruction were treated with PTA and nine (75%) were treated with stent placement. Three children with IVC obstruction (75%) were treated with PTA and one (25%) was treated with a stent. There were two children with simultaneous obstruction at the HV and IVC; one was treated with PTA and the other with a stent. Cases of isolated HV stenosis have a higher probability of patency with balloon-expandable stent treatment compared with balloon dilation (P < .05). Follow-up time ranged from 7 days to 9 years (mean, 42 months +/- 31), and the primary assisted patency rate was 100% when stent placement was performed among the first three procedures. CONCLUSIONS: In cases of venous outflow obstruction resulting from HV and/or IVC lesions after pediatric liver transplantation, percutaneous endovascular treatment with balloon dilation or stent placement is a safe and effective alternative treatment that results in long-term patency.

FACTORS ASSOCIATED TO ADHERENCE TO DIFFERENT TREATMENT SCHEMES WITH MEGLUMINE ANTIMONIATE IN A CLINICAL TRIAL FOR CUTANEOUS LEISHMANIASIS

The favorable outcome of the treatment of a disease is influenced by the adherence to therapy. Our objective was to assess factors associated with adherence to treatment of patients included in a clinical trial of equivalence between the standard and alternative treatment schemes with meglumine antimoniate (MA) in the treatment of cutaneous leishmaniasis (CL), in the state of Rio de Janeiro. Between 2008 and 2011, 57 patients with CL were interviewed using a questionnaire to collect socioeconomic data. The following methods were used for adherence monitoring: counting of vial surplus, monitoring card, Morisky test and modified Morisky test (without the question regarding the schedule); we observed 82.1% (vial return), 86.0% (monitoring card), 66.7% (Morisky test) and 86.0% (modified Morisky test) adherence. There was a strong correlation between the method of vial counting and the monitoring card and modified Morisky test. A significant association was observed between greater adherence to treatment and low dose of MA, as well as with a lower number of people sleeping in the same room. We recommend the use of the modified Morisky test to assess adherence to treatment of CL with MA, because it is a simple method and with a good performance, when compared to other methods.

LAY USE OF AMAZONIAN PLANTS FOR THE TREATMENT OF TUBERCULOSIS

The Brazilian State of Amazonas has a high incidence of Tuberculosis, 91.4 in 10,000 habitants (SESAU, 1994) and resistant strains of Mycobacterium tuberculosis are frequently being found in the region (SALEM et.al, 1990). These problems have been associated with side effects caused by the antibiotics used to treat Tuberculosis, which have in rum been associated with treatment non-compliance (PATTISAPU, 1984). To resolve this problem a cost effective alternative treatment for Tuberculosis with few or no side effects, needs to be found. Amazonas has an abundance of plants, many of which are used by the lay population for medicinal purposes. A survey was carried out in five towns of the region, interviewing patients receiving treatment for Tuberculosis, to find out whether and which plants have been used to treat Tuberculosis. Results showed that the majority of patients in the sample had used medicinal plants before or after diagnosis of Tuberculoses. Thirteen different plants were recorded for this purpose. Chenopodium ambrosioides L, popularly known as Mastruz, was the most commonly used, followed by Caesalpinia ferrea Mart. Jucá and Spilanthes acmella DC. Jambu. This study concentrates on Mastruz as it was used more frequently than the other medicinal plants. No significant effects on baciloscopy test results were found when Mastruz was used before diagnosis. ln-vitro laboratory tests have also not shown any tuberculocidal effects for Mastruz. Further tests are being carried out on the other medicinal plants.

Epidemiological aspects of adherence to the treatment of hypertension

OBJECTIVE: To analyze the reasons given by patients for interrupting their pharmacological treatment of hypertension. METHODS: We carried out an observational cross-sectional study, in which a questionnaire was applied and blood pressure was measured in 401 patients in different centers of the state of Bahia. The patients selected had been diagnosed with hypertension and were not on antihypertensive treatment for at least 60 days. Clinical and epidemiological characteristics of the groups were analyzed. RESULTS: Of the 401 patients, 58.4% were females, 55.6% of whom white; 60.5% of the males were white. The major reasons alleged for not adhering to treatment were as follows (for males and females respectively): normalization of blood pressure (41.3% and 42.3%); side effects of the medications (31.7% and 24.8%); forgetting to use the medication (25.2% and 20.1%); cost of medication (21.6% and 20.1%); fear of mixing alcohol and medication (23.4% and 3.8%); ignoring the need for continuing the treatment (15% and 21.8%); use of an alternative treatment (11.4% and 17.1%); fear of intoxication (9.6% and 12.4%); fear of hypotension (9.6% and 12%); and fear of mixing the medication with other drugs (8.4% and 6.1%). CONCLUSION: Our data suggest that most factors concerning the abandonment of the treatment of hypertension are related to lack of information, and that, despite the advancement in antihypertensive drugs, side effects still account for most abandonments of treatment.

Immunochemotherapy in American cutaneous leishmaniasis: immunological aspects before and after treatment

In this study, we evaluated the immune response of patients suffering from cutaneous leishmaniasis treated with two distinct protocols. One group was treated with conventional chemotherapy using pentavalent antimonium salts and the other with immunochemotherapy where a vaccine against cutaneous leishmaniasis was combined with the antimonium salt. Our results show that, although no differences were observed in the necessary time for complete healing of the lesions between the two treatments, peripheral blood mononuclear cells from patients treated by chemotherapy showed smaller lymphoproliferative responses at the end of the treatment than those from patients in the immunochemotherapy group. Furthermore, IFN-gamma production was also different between the two groups. While cells from patients in the chemotherapy group produced more IFN-gamma at the end of treatment, a significant decrease in this cytokine production was associated with healing in the immunochemotherapy group. In addition, IL-10 production was also less intense in this latter group. Finally, an increase in CD8+ -IFN-gamma producing cells was detected in the chemotherapy group. Together these results point to an alternative treatment protocol where healing can be induced with a decreased production of a potentially toxic cytokine.

Intravenous lacosamide for treatment of status epilepticus.

Objectives -  Treatment of established status epilepticus (SE) requires immediate intravenous anticonvulsant therapy. Currently used first-line drugs may cause potentially hazardous side effects. We aimed to assess the efficacy and safety of intravenous lacosamide (LCM) in SE after failure of standard treatment. Methods -  We retrospectively analyzed 39 patients (21 women, 18 men, median age 62 years) from the hospital databases of five neurological departments in Germany, Austria and Switzerland between September 2008 and January 2010 who were admitted in SE and received at least one dose of intravenous LCM. Results -  Types of SE were generalized convulsive (n = 6), complex partial (n = 17) and simple partial (n = 16). LCM was administered after failure of benzodiazepins or other standard drugs in all but one case. Median bolus dose of LCM was 400 mg (range 200-400 mg), which was administered at 40-80 mg/min in those patients where infusion rate was documented. SE stopped after LCM in 17 patients, while 22 patients needed further anticonvulsant treatment. The success rate in patients receiving LCM as first or second drug was 3/5, as third drug 11/19, and as fourth or later drug 3/15. In five subjects, SE could not be terminated at all. No serious adverse events attributed to LCM were documented. Conclusions -  Intravenous LCM may be an alternative treatment for established SE after failure of standard therapy, or when standard agents are considered unsuitable.

Intravenous Lacosamide for Treatment of Status Epilepticus after Failing First-Line Therapy

Rationale: Treatment of status epilepticus (SE) usually requires intravenous anticonvulsant therapy. Although there are established drugs of first choice for its treatment, potentially hazardous side effects of these agents are not uncommon. Lacosamide (LCM) is a novel anticonvulsant drug that is available as infusion solution. LCM could be an alternative for treatment of SE when the standard drugs fail or should be avoided. Methods: We retrospectively identified patients from the hospital databases of two German and one Swiss neurological departments (University Hospital Marburg, Klinikum Osnabrueck, University Hospital Lausanne) between September 1st 2008 and May 22nd 2009 who were admitted because of SE and received at least one dose of intravenous LCM for treatment of SE. Results: Seventeen patients (11 female, 6 male) were identified. Median age was 71 years. 3 patients suffered from generalized convulsive SE, 8 patients had significant reduction of awareness with or without subtle motor symptoms, 6 patients had a simple focal status without relevant reduction of awareness. Etiology was acute symptomatic in 5 patients, remote symptomatic without pre-existing epilepsy in 6 patients, remote symptomatic and pre-existing epilepsy in 5 patients, and unknown in 1 patient. LCM was administered after failure of first line therapy in all cases. The first LCM bolus was 400mg in 13 patients and 200mg in 4 patients. LCM administration stopped SE in 7 patients. In 2 of them, LCM was administered immediately after benzodiazepine administration, in the others after failure of benzodiazepines and other first-line and/or second-line drugs. In 3 patients, SE was terminated by other anticonvulsants like Phenytoin, Phenobarbital or Oxcarbazepine. In 5 patients, SE could only be terminated by intubation and application of high-dose Midazolam, Propofol and/or Thiopental. In 2 patients, SE could not be terminated in spite of high doses of barbiturates. There was no serious adverse event documented that could possibly be attributed to LCM Conclusions: Intravenous LCM may be an alternative treatment for SE after failure of benzodiazepins and other established drugs, or when such agents are considered unsuitable.

Canakinumab (ACZ885) vs triamcinolone acetonide for treatment of acute flares and prevention of recurrent flares in gouty arthritis patients refractory to or contraindicated to nsaids and/or colchicine.

Purpose: Current treatments for arthritis flares in gout (gouty arthritis) are not effective in all patients and may be contraindicated in many due to underlying comorbidities. Urate crystals activate the NALP 3 inflammasome which stimulate production of IL-1β, driving inflammatory processes. Targeted IL-1β blockade may be an alternative treatment for gouty arthritis. Canakinumab (ACZ885) is a fully human monoclonal anti- IL-1β antibody with a long half-life (28 days). Method: This was an 8-weeks, dose-ranging, multicenter, blinded, double-dummy, active-controlled trial of patients ≥18 to ≤80 y with an acute gouty arthritis flare, refractory to or contraindicated to NSAIDs and/or colchicine. Patients were randomized to 1 subcutanous (sc) dose of canakinumab (10, 25, 50, 90, or 150 mg) or 1 intra muscular (im) dose of triamcinolone acetonide (TA) [40 mg]. The primary variable was assessed 72 h post-dose, measured on a 0-100 mm VAS pain scale. Secondary variables included pain intensity 24 and 48 h post dose, time to 50% reduction in pain intensity, and time to recurrence of gout flares up to 8 weeks post dose. Results: 200 patients were enrolled (canakinumab n=143, TA n=57) and 191 completed the study. A statistically significant dose response was observed at 72 h. The 150 mg dose reached superior pain relief compared to TA starting from 24h: estimated mean difference in pain intensity on 0-100 mm VAS was -11.5 at 24 h, -18.2 at 48 h, and -19.2 at 72 h (all p<0.05). Canakinumab 150 mg provided a rapid onset of pain relief: median time to 50% reduction in pain was reached at 1 day with canakinumab 150 mg vs 2 days for the TA group (p=0.0006). The probability of recurrent gout flares was 3.7% with canakinumab 150 mg vs. 45.4% with TA 8 weeks post treatment, a relative risk reduction of 94% (p=0.006). Serious AEs occurred in 2 patients receiving canakinumab (appendicitis and carotid artery stenosis) and 1 receiving TA (cerebrovascular disorder). Investigator's reported these events as not study drug related. There were no discontinuations due to AEs. Conclusion: Canakinumab 150 mg provided faster onset and superior pain relief compared to TA for acute flares in gouty arthritis patients refractory to or contraindicated to standard treatments. The 150 mg dose of canakinumab prevented recurrence of gout flares with a relative risk reduction compared to TA of 94% at 8 weeks post-dose, and was well tolerated.

Encapsulated, genetically engineered cells, secreting glucagon-like peptide-1 for the treatment of non-insulin-dependent diabetes mellitus.

Non-insulin-dependent, or type II, diabetes mellitus is characterized by a progressive impairment of glucose-induced insulin secretion by pancreatic beta cells and by a relative decreased sensitivity of target tissues to the action of this hormone. About one third of type II diabetic patients are treated with oral hypoglycemic agents to stimulate insulin secretion. These drugs however risk inducing hypoglycemia and, over time, lose their efficacy. An alternative treatment is the use of glucagon-like peptide-1 (GLP-1), a gut peptidic hormone with a strong insulinotropic activity. Its activity depends of the presence of normal blood glucose concentrations and therefore does not risk inducing hypoglycemia. GLP-1 can correct hyperglycemia in diabetic patients, even in those no longer responding to hypoglycemic agents. Because it is a peptide, GLP-1 must be administered by injection; this may prevent its wide therapeutic use. Here we propose to use cell lines genetically engineered to secrete a mutant form of GLP-1 which has a longer half-life in vivo but which is as potent as the wild-type peptide. The genetically engineered cells are then encapsulated in semi-permeable hollow fibers for implantation in diabetic hosts for constant, long-term, in situ delivery of the peptide. This approach may be a novel therapy for type II diabetes.

IV paracetamol versus IV ibuprofen for the treatment of PDA in LBW infants: a randomized controlled trial

Patent ductus arteriosus is a prevalent problem in low birth weight infants and it has an important morbidity and mortality in this group of patients. Classical treatment options include drugs (intravenous cyclooxygenase inhibitors: indomethacin and ibuprofen) and surgical ligation, but these treatments are associated with significant adverse effects. An alternative treatment with fewer side effects is needed. The role of oral paracetamol has gained importance in recent years, this new therapeutic option is being widely studied, and there are already many studies which support oral paracetamol as first line treatment for PDA, due to its better safety profile than classical drugs. In LBW infants is difficult to administer enteral treatment, since they are often multi pathological patients with several complications that preclude oral administration and they usually receive intravenous treatments. This multicenter, prospective, single blinded, randomized, controlled, parallel-group and noninferiority trial is designed to evaluate the efficacy and safety of intravenous paracetamol versus intravenous ibuprofen in the treatment of PDA in LBW infants. Sixty eight infants with echocardiography confirmed PDA will be randomly assigned to receive either intravenous paracetamol or intravenous ibuprofen. The main endpoints will be the rate of ductal closure of each drug and adverse events in each group of treatment

Treatment of mature urban landfill leachates by anammox process

This thesis results from the collaborative projects between the LEQUIA-UdG group and Cespa (a company in charge of several landfill sites in Spain). The aim of the work was the development of a suitable alternative treatment for nitrogen removal from mature landfill leachates. The thesis presents the application of the anammox (anaerobic ammonium oxidation process) process to treat ammonium rich leachates as the second step of the PANAMMOX® process. The work deals with preliminary studies about the characteristics of the anammox process in a SBR, with special focus on the response of the biomass to nitrite exposure. The application of the anammox process with leachate was first studied in a lab-scale reactor, to test the effect of the leachate matrix on anammox biomass and its progressive adaptation. Finally, a start-up strategy is developed and applied for the successful start-up of a 400L anammox SBR in less than 6 months.

Clinical and Microbiologic Follow-Up Evaluations After Non-Surgical Periodontal Treatment With Erbium:YAG Laser and Scaling and Root Planing

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Ultrasound efficiency in relation to sodium hypochlorite and filtration adsorption in microbial elimination in a water treatment plant

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Comparative study between photodynamic and antibiotic therapies for treatment of footpad dermatitis (bumblefoot) in Magellanic penguins (Spheniscus magellanicus)

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)