How logrolling can explain the failure of the government coalition in Brazil

This article presents an analysis of the behavior of federal representatives in the Brazilian House of Representatives between 1995 and 1998, when a series of constitutional amendments were presented by the president to be voted on by Congress. The objective is to show that the lack of a stable government coalition resulted in costs to society that were not anticipated by the government. The study argues that a logroll - a trade of votes - was the strategy used by the government in order to guarantee the number of votes necessary to approve the amendments. This strategy created a vicious system in which representatives would only vote with the government if they had benefits in return.

Failure of nitric oxide production by macrophages and decrease in CD4+ T cells in oral paracoccidioidomycosis: possible mechanisms that permit local fungal multiplication

Paracoccidioidomycosis is a chronic granulomatous disease that induces a specific inflammatory and immune response. The participation of nitric oxide (NO), a product of the inducible nitric oxide synthase enzyme (iNOS), as an important fungicidal molecule against Paracoccidioides brasiliensis has been demonstrated. In order to further characterize the Oral Paracoccidioidomycosis (OP), we undertook an immunohistochemical study of iNOS+, CD45RO+, CD3+, CD8+, CD20+, CD68+ cells and mast cells. The samples were distributed in groups according to the number of viable fungi per mm². Our results showed weak immunolabeling for iNOS in the multinucleated giant cells (MNGC) and in most of the mononuclear (MN) cells, and the proportion of iNOS+ MN/MNGC cells in the OP were comparable to Control (clinically healthy oral tissues). Additionally, our analysis revealed a similarity in the number of CD4+ cells between the Control and the OP groups with higher numbers of fungi. These findings suggest that a low expression of iNOS and a decrease in the CD4+ T cells in OP may represent possible mechanisms that permit the local fungal multiplication and maintenance of active oral lesions.

Failure of both azithromycin and antimony to treat cutaneous leishmaniasis in Manaus, AM, Brazil

A non-randomized controlled clinical trial was carried outin order to evaluate both azithromycin and antimony efficacy in cutaneous leishmaniasis in Manaus, AM, Brazil. Forty nine patients from both genders, aged 14 to 70, with cutaneous ulcers for less than three months and a positive imprint for Leishmania spp. amastigotes were recruited into two groups. Group I (26 patients) received a daily-single oral dose of 500 mg of azithromycin for 20 days and Group II (23 patients) received a daily-single intramuscular dose of 20 mg/kg of meglumine antimony, also for 20 days. Azithromycin cured three of 24 (12.5%) patients on days 60, 90 and 120 respectively whereas therapeutic failure was considered in 21 of 24 (87.5%) cases. In group II, antimony cured eight of 19 (42.1%) cases as follows: three on day 30, one each on day 60 and day 90, and three on day 120. Therapeutic failure occurred in 11 of 19 (57.9%) individuals. The efficacy of antimony for leishmaniasis was better than azithromycin but analysis for the intention-to-treat response rate did not show statistical difference between them. Although azithromycin was better tolerated, it showed a very low efficacy to treat cutaneous leishmaniasis in Manaus.

Study of Schistosoma mansoni isolates from patients with failure of treatment with oxamniquine

After three successive treatments with oxamniquine the continuing elimination of Schistosoma mansoni eggs was observed in patients, who came from various regions of Brazil, with different clinical forms of schistosomiasis. The objective of the present study was to determine the experimental behaviour of five different S. mansoni isolates in Swiss Webster mice that were submitted to treatment with the same drug. The experimental group with failure of treatment showed higher mean number of surviving male worms when it was compared to the group without failure of treatment. These date suggest the possibility of resistance to oxamniquine.

Therapeutic failure of praziquantel in the treatment of Schistosoma haematobium infection in Brazilians returning from Africa

Several cases of therapeutic failure of praziquantel used for the treatment of urinary schistosomiasis have been reported. Alternative drugs, like niridazol and metrifonate, have shown a lower therapeutic effect and more side effects than praziquantel. Twenty-six Brazilian military men (median age of 29 years) with a positive urine parasitological exam who were part of a United Nation peace mission in Mozambique in 1994 were treated with 40 mg/kg body weight praziquantel, single dose. They swimmed in Licungo river (Mocuba city, Mozambique) during the weekends. After this, they presented haematuria, dysuria, polakiuria, and lumbar pain. Control cystoscopy examinations carried out between 6 and 24 months after each treatment (including two additional treatments at a minimum interval of 6 months) revealed the presence of viable eggs. Granulomas in the vesical submucosa were observed in 46.2% (12/26) of the individuals. A vesical biopsy confirmed the presence of granulomas in all of these patients and the presence of viable eggs in 34.3% (9/26) of individuals who no longer excreted eggs in urine. The eggs filled with miracidia showed characteristics of viability. Histopathological examination using different strains demonstrated therapeutic failure and the need for repeated treatment. In this study, we demonstrated a low efficacy of praziquantel in the treatment of schistosomiasis haematobia, and the necessity of the urinary bladder biopsy as criterion of cure.

Failure of neutrophil migration toward infectious focus in severe sepsis: a critical event for the outcome of this syndrome

Sepsis is a systemic inflammatory response commonly caused by bacterial infection. We demonstrated that the outcome of sepsis induced by cecal ligation and puncture (CLP) correlates with the severity of the neutrophil migration failure towards infectious focus. Failure appears to be due to a decrease in the rolling and adhesion of neutrophil to endothelium cells. It seems that neutrophil migration impairment is mediated by the circulating inflammatory cytokines, such as TNF-alpha and IL-8, which induce the nitric oxide (NO) production systemically. It is supported by the fact that intravenous administration of these cytokines reduces the neutrophil migration induced by different inflammatory stimuli, and in severe sepsis the circulating concentrations of the cytokines and chemokines are significantly increased. Moreover, the neutrophil migration failure and the reduction in the rolling/adhesion were not observed in iNOS-/- mice and, aminoguanidine prevented this event. We also demonstrated that the failure of neutrophil migration is a Toll-4 receptor (TLR4) dependent mechanism, since it was not observed in TLR4 deficient mice. Furthermore, it was also observed that circulating neutrophils obtained from septic patients present failure of neutrophil chemotaxis toward fMLP, IL-8, and LTB4 and an increased in sera concentrations of NO3 and cytokines. In conclusion, we demonstrated that, in sepsis, failure of neutrophil migration is critical for the outcome and that NO is involved in the process.

Low expression of APAF-1XL in acute myeloid leukemia may be associated with the failure of remission induction therapy

Apoptotic protease activating factor 1 (APAF-1) has a critical role in the regulation of apoptosis. In the present study, the mRNA expression analysis of different APAF-1 transcripts (APAF-1S, APAF-1LC, APAF-1LN, and APAF-1XL) was analyzed in bone marrow samples from 37 patients with acute myeloid leukemia (newly diagnosed, with no previous treatment). APAF-1XL and APAF-1LN transcripts (with and without an extra WD-40 repeat region, respectively) were detected in all samples, although the major form expressed was APAF-1XL in 65% of the samples (group 1), while 35% of the samples expressed primarily APAF-1LN (group 2). Only 46% of the patients presented complete remission in response to remission induction therapy (represented by less than 5% marrow blasts and hematological recovery), all but 2 cases being from group 1, 21.6% did not attain complete remission (only 1 case from group 1), and 32.4% of the patients died early. Lower expression of APAF-1XL (APAF-1XL/APAF-1LN ratio <1.2) was associated with a poor response to therapy (P = 0.0005, Fisher exact test). Both groups showed similar characteristics regarding white blood cell counts, cytogenetic data or presence of gene rearrangements associated with good prognosis as AML1-ETO, CBFB-MYH11 and PML/RARA. Since it has been shown that only the isoforms with the extra WD-40 repeat region activate procaspase-9, we suggest that low procaspase-9 activation may also be involved in the deregulation of apoptosis and chemotherapy resistance in acute myeloid leukemia.

Prevention of bone marrow graft failure by an anti LFA-1 monoclonal antibody

Graft rejection is the major cause of failure of HLA mismatched bone marrow transplantation because of residual host immunity. we have proposed to use a monoclonal murine antibody specific for the LFA-1 molecule (25-3) to prevent graft failure in HLA mismatched bone marrow transplantation (BMT). The rationale for this approach is three fold: LFA-1 deficient patients (3/3) do not reject HLA mismatched BMT; anti LFA-1 blocka in vitro the induction of T cell responses and T/ non T cytotoxic functions; LFA-1 is not expressed by other cells than leucocytes. We have accordingly treated twenty two patients with inherited diseases and 8 with leikemia. The bone marrow was T cells depled by E rosetting of Campath antibody. The antibody was given at days -3, -1, +1, +3, +5 at dose of .1 mg/kg/d for the first 9 and then .2mg/kg/d from day -3 to +6. Engraftment occured in 23/30 patients as shown by at least HLA typing. Hematological recovery was rapid, GVH was limited. Side effects of antibody infusion included fever and possibly an increased incidence of early bacteral infection (sepsis, 1 death). Immunological reconstitution occured slowly leading in six cases to EBV-induced B cell poliferation (1 death and in two others to transient auto immune hemolytic anemia. There has been only one secondary graft rejection. Sisteen patients are alive 3 to 26 months post transplant with functional grafts. Although the number of patients treated is still low the absence of late rejection so far, gives hope for long term maintenance of the graft using anti LFA-1. Since the antibody is an IgG 1 unable to bind human complement, and since it is known to inhibit phagocytosis, there is a good suggestion that 25-3 act through functional blocking of host T and non T luymphocytes at both induction and effector levels.

Reduction of the amount of intestinal secretory IgA in fulminant hepatic failure

Intestinal barrier dysfunction plays an important role in spontaneous bacterial peritonitis. In the present study, changes in the intestinal barrier with regard to levels of secretory immunoglobulin A (SIgA) and its components were studied in fulminant hepatic failure (FHF). Immunohistochemistry and double immunofluorescent staining were used to detect intestinal IgA, the secretory component (SC) and SIgA in patients with FHF (20 patients) and in an animal model with FHF (120 mice). Real-time PCR was used to detect intestinal SC mRNA in the animal model with FHF. Intestinal SIgA, IgA, and SC staining in patients with FHF was significantly weaker than in the normal control group (30 patients). Intestinal IgA and SC staining was significantly weaker in the animal model with FHF than in the control groups (normal saline: 30 mice; lipopolysaccharide: 50 mice; D-galactosamine: 50 mice; FHF: 120 mice). SC mRNA of the animal model with FHF at 2, 6, and 9 h after injection was 0.4 ± 0.02, 0.3 ± 0.01, 0.09 ± 0.01, respectively. SC mRNA of the animal model with FHF was significantly decreased compared to the normal saline group (1.0 ± 0.02) and lipopolysaccharide group (0.89 ± 0.01). The decrease in intestinal SIgA and SC induced failure of the intestinal immunologic barrier and the attenuation of gut immunity in the presence of FHF.

Soft tissue abscess and lymphadenitis due to Mycobacterium avium Complex as an expression of immune reconstitution inflammatory syndrome after a second scheme of highly active antiretroviral therapy

Immune reconstitution inflammatory syndrome (IRIS) is an atypical and unexpected reaction related to highly active antiretroviral therapy (HAART) in human immunodeficiency virus (HIV) infected patients. IRIS includes an atypical response to an opportunistic pathogen (generally Mycobacterium tuberculosis, Mycobacterium avium complex, cytomegalovirus and herpes varicella-zoster), in patients responding to HAART with a reduction of plasma viral load and evidence of immune restoration based on increase of CD4+ T-cell count. We reported a case of a patient with AIDS which, after a first failure of HAART, developed a subcutaneous abscess and supraclavicular lymphadenitis as an expression of IRIS due to Mycobacterium avium complex after starting a second scheme of HAART.

Induction of male sterility through manipulation of genetic mechanisms present in vector species of Triatominae. II. Partial restoration of male fertility

The development of integrated measures which involve sterile mate release to supplement the conventional insecticidal techniques used in controlagainst insects of medical importance, raised the question, whether the vectors of Chagas'disease possess the natural mechanisms by manipulation of which they may be controlled. Results of earlier expenments, that had been published previously, were restricted to fragmentary information that raised various questions, the answer to which became available in the study herein described. Interspecific hybrids were produced from reciprocal crosses between T. pseudomaculata and T. sórdida and from unilateral crosses between female T. pseudomaculata and male. T. infestans. These females mated with males, laid less than the normal complement of eggs, but offspring was relatively abundant. When T. pseudomaculata females were paired with T. brasiliensis males, hybridization was more difficult because few of the females mated and those that did had a strongly reduced fertility. Adults emerged from ali crosses but exhibited sex disproportion, females predominating in all populations but one. The two Rhodnius species tested were also found to cross, but only when female R. prolixus were paired with male R. neglectus. These females laid a relatively high complement o f eggs, had a strongly reduced fertility, but 50% of the fertile eggs developed into vigorous adults, males predominating females. Neither type of hybrid male elicited fertilized eggs from either parental type of female, through their vesicula seminal is were found to be packed with spermatozoa, some normal looking and moving, others underdeveloped and motionless. Although, no artificial insemination was performed, the sperm in itself did not appear to be the prime inducer of sterility. Females paired with these hybrids did mate, sperm was transfered, as evidenced by the discharged spermatophores smeared with sperm, but did notcontain spermatozoa in their spermatecae. The failure of the sperm to migrate to the spermatecae indicate prezygotic pos-copulation incompatibility, thus the hybrid male can't be used to suppress populations. The female hybrids mated with parent males of either species had reduced fertility and ther sons were sterile as were those of their fertile daughters. However, continous backcrossing of the hybrid females and their female progeny to parental males partially restored fertility of the males and increased fertility of females, as scored by egg hatchability. Fertility of hybrid females, measured by the yield of adults capable to reproduce, indicated that the reproductive perfomance decreased when hybrid females and their daughters were backcrossed additional generations to parental males. It is tentatively suggested that hybrid females could be used for suppression if they compete efficiently with wild females.

Treatment of T. cruzi infected human platelet concentrates with aminomethyltrimethyl psoralen (AMT) and ultravioleta (UV-A) light: preliminary results

The present measures adopted to prevent transfusion-associated Chagas' disease include screening of blood donors. and/or the inactivation of T. cruzi in collected blood using gentian violet (GV) as a trypanocidal agent. In this study, we investigated the efficacy of the combined use of AMT and UV-A in inactirating T. cruzi in infected human platelet cuncentrates. Human platelet concentrates were infected with T. cruzi (2x10/ml) of the Y strain transfered to PL 269 (Fenwal Laboratories) containers and treated with GV (250řg,/ml). and ascorbic acid (1 mg/ml); GV. ascorbic acid and UV-A; GV and UV-A; AMT (40/tG/ml) and ascorbic acid; AMT, ascorbic acid and UV-A; AMT and UV-A; UV-A alone; and untreated (control). All UV-A treated platelet concentrates were exposed to UV-A doses of 24, 92, 184, 276, 368 and 644 kj/m². and the microscopical research of active T. cruzi was performed, using the microhematocrit technique, 1, 6 and 24 hours after each treatment. A high number of active forms of T. cruzi was observed in all condictions, except when GV was used as the trypanocidal agent, providing evidence of the failure of AMT and UV-A in inactivating T cruzi in infected human platelet concentrates.

Successful therapeutic response of resistant cases of mucocutaneous leishmaniasis to a very low dose of antimony

Two mucocutaneous leishmaniasis cases resistant to therapy are reported here. After the failure of initial therapies (antimony, amphotericin B and/or pentamidine) patients received a low-dose schedule: one ampoule of meglumine antimoniate (405mg of pentavalent antimony [Sb v]) by intramuscular injection, three times a week until complete healing of the lesions. One patient was cured with a total of 30 ampoules in 10 weeks and the other received 36 ampoules in 12 weeks. Both remain clinically cured after one year of follow-up.

Low prevalence of hepatitis B virus, hepatitis D virus and hepatitis C virus among patients with human immunodeficiency virus or acquired immunodeficiency syndrome in the Brazilian Amazon basin

Comorbidities in human immunodeficiency virus infection are of great interest due to their association with unfavorable outcomes and failure of antiretroviral therapy. This study evaluated the prevalence of coinfection by human immunodeficiency virus and viral hepatitis in an endemic area for hepatitis B in the Western Amazon basin. Serological markers for hepatitis B virus, hepatitis C virus and hepatitis D virus were tested in a consecutive sample of all patients referred for treatment of human immunodeficiency virus or acquired immunodeficiency syndrome. The variables sex, age, origin and exposure category were obtained from medical records and from the sexually transmitted diseases and acquired immunodeficiency syndrome surveillance database. Among 704 subjects, the prevalence of chronic hepatitis B carriage was 6.4% and past infection 40.2%. The presence of hepatitis B was associated with birth in hyperendemic areas of the Amazon basin, male sex and illegal drug use. The overall prevalence of hepatitis C was 5% and was associated with illegal drug use. The prevalence of hepatitis B and C among human immunodeficiency virus or acquired immunodeficiency syndrome patients in the Western Amazon basin was lower than seen elsewhere and is probably associated with the local epidemiology of these viruses and the degree of overlap of their shared risk factors. An opportunity presents itself to evaluate the prevention of hepatitis C through harm reduction policies and hepatitis B through vaccination programs among human immunodeficiency virus or acquired immunodeficiency syndrome patients.